Updates & online help through forums are only available to those who purchased this book from the author at http://www.adichemistry.com/ 1 ADICHEMISTRY SOLVED PROBLEMS IN ADVANCED ORGANIC SYNTHESIS (FOR CSIR NET & GATE) 1st EDITION Release date: 7th, May 2012 Last updated on: 25th April 2013 No. of problems solved: 215 No. of pages: 183 zg = 5 z z s of CSIR NET, SLET, APSET, GATE, lIScand other University entrance exams. Most of the advanced level problems in organie synthesis from previous year question papers are solved and are thoroughly explained with mechanisms. It is a dynamic on-line version; updated frequently. You can purchase this book at different rates depending on your choice. PRICE DETAILS, OPTION-1 Rs. 1025/- (if you purchase at this rate, free updates are NOT available. However you can get free updates by contributing your knowledge on forumand by helping the author, For more details contact at the following mail id.) OPTION-2 Rs. 1400/- (ifyou purchase at this rate, you will get free updates up to 31st December 2013). TO KNOW THE METHOD OF PAYMENT MAIL ME AT ADICHEMADI@GMAIL.COM Note: Updates & support through forums are only available to those who purchased this book from the author of this book at his site: http://www.adichemistry.com, Problem 1.1 (IISc 2011) °o OL i) PhMgBr om iy" eee ye ty °) Ph ad) Ph On On OQ a, Answer: ¢ IP JOU Og “AUD AnysHUOYoIPE:ALALAYy/sdhyy WHOA, A[UO aIgeHEAL St YOO stIp Jo Adoo pourLI0 ay a g & z E SsExplanation ° 1) Pager 1,2 addition of Grignard reagent BrMgO__,Ph :/Iwww.adichemistry.con’ Z E 3 & e g & = E g & z B z acid catalysed and conjugate bond assisted removal of OH group final removal step of EtOH ‘Think different: What will happen if 1,4 addition occurs? OH O° fe} . Om Oe Og OL oN OH oN oO ELOH Ph 1, 4 addtion of PhMgBr ‘Joye Jo UoISssUad Moy Yoo stIp aINgUNSIP YoU Og “/AtOD-CnsTUDYDAPE-ALAL Same product! So it might be the actual mechanism? But slim chances. Why? The possible explanation right go like this: i) the positive charge on 4th position is diminished due to contribution of p-electrons of adjacentethoxy ‘O’ through conjugation (+M effect). Updates & online help through forums are only available to those who purchased this book from the author at it3 ii) The enolate ion formis less stable due to -Leffect of 0”. Z Wealso know that: 1,2 addition is kinetically more favorable than 1,4-addition incase of Grignard 8 reagents. It is because the R group attached to Mg in GR is a hard nucleophile and prefers carbonyl carbon with considerable positive charge (hard electrophile). And if this is the mechanism, the removal of ethanol may give another product, though less likely, as shown below. Q,, Now start arguing! Web Resource: http:/Avwwadichemistry.com/organic/onganicreagents’grignard grignard-reagent-reaction- 1.html :/Iwww.adichemistry.com’ z 3 3 E g & 5 EB E g g ¢ 3 z Problem 1.2 The most appropriate set of reagents for carrying out the following conversion is: AP + onion a) i) EtMgBr, ii) HCL b) i) (C,H),CuLi; ii) HCL ci) CHLi; ii) HCL d)i) HCI, ii) EtMgBr Answer: d Explanation: | 4-addition of HCL furnishes 4-chlorobutanone, which reacts with Grignard reagent to get the desired product. ro ap HCl cl. 0 EtMgBr H,0" Gy ‘OH AL ail alae However, the yields may not be satisfactory due to side reaction that is possible in the second step with Grignard reagent. It may undergo Wurtz like coupling reaction with -CH,Cl group. cl 0 EtMgBr ° 6 — —_ > + MgBrCl What about other options? ‘JoUNe Jo uo|SssTULIad joy 400g StI AINgLSIp OU OC_“;UIOD-CnsHHIOYDIPE-ALAL Option -a: Updates & online help through forums are only available to those who purchased this book from the author at ht. major product V O etMgsr—H,0° oH HCI af cl . - cr HO. cr “af * |,2-addition occurs with Grignard reagent, since the ethyl group attached to Mg has considerable ae positive charge and is a hard nucleophile. It prefers to attack 2nd carbon (hard electrophile). * In the reaction ofallylic alcohol with HCl, the Ct prefers to attack the allylic carbocation from less. hindered end. Hence the major product is 1-chloro-3-methyl-2-pentene. + 5 :/Iwww.adichemistry.com’ hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, Option -b Are Ft Culi—H,0" 0 Hel oY BO OHSS esos ld reaction 1 4-addition occurs with Lithium diethyl cuprate, since ethyl group attached to copper isa soft nucleophile and prefers carbon at 4th position (soft electrophile) Option-e: ‘The products are same as in case of option-a, Ethyllithium also shows 1,2 addition like G reagent Problem 1.3 (CSIR DEC 2011) Choose the correct option for M & N formed in reactions sequence given below. 9 & = i 2 3 3 gz zg a g & & E Z g é g 1) BH, SMe, 1)PhMgBr 2) PCC ———> m—_—__+n 2)TsOH 3) mCPBA HO Ph ph 0 a) Me b) Me O°? Ph Phy Answer: a Explanation: * Atertiary alcohol is formed upon 1,2 addition of PhMgBr and is dehydrated in presence of Tosylic acid. Updates & online help through forums are only available to those who purchased this book from the author at hitHO. Ph Ph PhMgBr H;0" TsOH +H,0 * Thus formed product is subjected to hydroboration with BH, Me,S complex to yield 2- phenyicyclohexanol, an anti-Markonikov’s product, which is oxidized to a ketone in presence of PCC. hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, = _ The keto compound is subjected to Baeyer Villiger oxidation with mCPBA to get a lactone. The g PhCH- group is migrated onto oxygen in preference to CH, group. § Baeyer Villger 2 oxidation : aa BH, SMe, Ao Pcc oe mCPBA Ch 2 ‘Anti Markonikov's Ph-CH- group has more product migratory aptitude than CH, group Problem 1.4 (CSIR JUNE 2011) ‘The major product formed in the following transformation is: 9 1) MeMgCl, CuCl pn 2) AAO Ph * The Grignard reagent reacts with CuClto give Me,CuMgCl, an organocopper compound also known as Gilman reagent that is added to the a.,-unsaturated ketone in 1,4-manner. Initially copper associates with the double bond to give a complex, which then undergoes oxidative addition followed by reductive elimination. Thus formed enolate ion acts asa nucleophile and substitutes the C1 group of allyl chloride. The attack on allyl chloride is done from the opposite side of more bulky phenyl group, 2 MeMgCl + Cuc- —» Me,CuMgC! + MgCl, & i 3 3 2 zg g & 2 z A & 7 Updates & online help through forums are only available to those who purchased this book from the author at hitZz 8 9 Me MMe 3 Mgct Me,CuMgCl uo} cu) . ze a Zo > 20 -O MgCl g een Ph ph N77 3 3 1 radon = 8 -ct z g Zi Zon & € + Me : 2 Attack of alt cation | M&. \__5 Macl A ALS] 2 q {rom sterically less Nap? a E : hindered side. Ph Ph ze 2 z 2 | 0° 3 F J Me, : or “NZ SN 0= Ce Ph Ph Why 1,4-addition occurs with Gilman reagent? ‘The methyl group on copper isa softer nucleophile and hence prefers softer electrophile, The carbon at 4th position is less polar and hence is a softer electrophile. That is why the attack of Me groupoceurs, at 4th position. Whereas the carbonyl carbon is more polar and a hard electrophile. Note: The atoms with more polarity ie., high charge are harder, ‘Why not the O-end of the enolate ion forms bond with allyl group? The very polar O' end isa hard nucleophile whereas the CH’ end is a softer nucleophile. The allyl group with positive charge on carbons also a softer electrophile and hence the bond is formed preferentially between the C-end ofenolate and allyl group. Problem 1.5 (CSIR OLD MODEL PAPER) ‘The major product formed in the reaction, given below, is CN 4. EtMgBr a 2.H,0" Explanation: & = i 3 3 3 gz zg a g & & E Z g é g Updates & online help through forums are only available to those who purchased this book from the author at ht7 ee LN Mg8r HOH “NH, Et-MgBi WN Et MgB uy An imine salt complex imine Problem 1.7 (GATE 1991) Predict the major product in the following reaction. 2. i) CHMgBr ii) HO" :/Iwww.adichemistry.conv Explanation: * The product mixture contains both axial and equatorial alcohols in equal proportions. There is no diastereoselectivity observed during this addition reaction due to steric and stereoelectronic effects ‘operating equally. hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, Hy axial 8 B+ attack ~ CH aMaBr OH 51% Co" ae Ho attack CH; 49% * When steric factor alone is considered, the moderately bulkier methylmagn to attack the cyclohexane ring from the convex side ie. equatorial. However this steric factor is cancelled out by stereoelectronic effect which favors axial attack ofGR.The 7 stereoelectronic effect can be explained by relatively stronger hyperconjugative interaction between a- ‘MO of incipient CH,-C bond and o*-MO of axial C-H bond on the adjacent carbon during late transition state when the GR approaches axially. 5 z i 6 2 zg 3 & & g a 8 3 2 g & 5 soypne jo woysssiuusad mnoyass yoo, _MaBr HAA o-MO of incipient CH,;C bond ye Relatively stronger hyperconjugative interaction between a-MO of incipient CH,-C bond and o*-MO axial C-H bond "MO of axial C-H bond during axial attack. Hyperconjugative interaction between -MO of incipient CH ,-C bond and o*-MO of ring C-C bond is also possible during equatorial attack. However this is relatively less effective and hence axialattack is more favored on stereoelectronie grounds. Updates & online help through forums are only available to those who purchased this book from the author at ht0 Z c-MO of incipient CH,-C bond Relatively weaker hyperconjugative interaction between c-MO of incipient / Mger CH,;C bond and o*-MO of ring C-C bond during equatorial attack. mp Jo $doo youist40 a4, 6°-MO of ring C-C bond However steric factor will outweigh stereoelectronic factor and improves the diastereoselectivity by & favoring more equatorial attack, ifalkylmagnesium sulfonates (otherwise knowns Reetz-Grignard reagents) are used. The larger the sulfonate group, the more it favors an equatorial approach. st Problem 1.8 of the following options is the most likely product formed in the following reaction? :/Iwww.adichemistry.conv g 2 E 5 8 & ¢ 5 F 1) Brg S98 2) H,0° ‘OH ‘OH ‘OH g HO, HO. HO. HO. g ) 2) 3) 4) \ 5 oH ° a a Answer: 4 5 3 Explanation: 8 * In this reaction, a lactone is made to react with a bis-Grignard reagent to get a diol. One of the 5 alcoholic group is tertiary and is derived from the carbonyl group of lactone. The other hydroxyl group is primary and takes on shape from the ring oxygen of lactone. This coversion is akin to the reaction of esters with excess of GR. ong ar o ° aan ° ger 12: MgBr ‘omer SO ‘OMgBr Updates & online help through forums are only available to those who purchased this book from the author at hit Jone Jo UOISsstUad jOyPLAL YOO SIP aINgUAsIP 0M O44 Problem 2.1 (GATE 2012) $ a KOH zB — what is the major product? = EtOH 2 ° 3 —- a) b) °) d 9 & g i o ‘CHO z B answer: b 3 g 2 g 8 z é 2 3 Explanation fo z ‘The a-hydrogen adjacent to ketone is more acidic and hence abstracted by base. Why not the other a-hydrogens are abstracted? Any INTRA MOLECULAR ALDOL REACTION ‘The -CHO group is more electrophilic and is attacked by the C-end of enolate ion. Oo 2 —}=%0 e i 8 é 3 zg & 2 g & é g i 2 & 7 Dehydration through E1cB mechanism. Updates & online help through forums are only available to those who purchased this book from the author at ht10 Web Resource: http:/;vww.adichemistry.com/organic/namedreactions/aldoValdok-addition-condensation-1 html ‘Think different: Why not other a-hydrogens are abstracted leading to different products? There are three different types of a-hydrogens, one adjacent to -CHO group and two adjacent to keto group. Ifthese hydrogens are abstracted, three different types of products are possible as explained 2 below. However formation of 7-membered ring is not favorable due to entropy considerations, even though the abstraction of proton from CH, group adjacent to keto group is kinetically favored. Abstraction ofproton adjacent to -CHO group ako leads to formation of five membered ring. But keto group is less electrophilic and the equilibrium does not move in forward direction, ‘doo youist40 a4, 6 Ee g & 5 E 5 8 & ¢ 5 F :/Iwww.adichemistry.conv Abstraction oF Hi Abstraction of H-1 0. of H-3 [Abstraction of H-2 \ Updates & online help through forums are only available to those who purchased this book from the author at hit 9° ° O: = 5 ‘Joye Jo UoISssUad Moy Yoo stIp aINgUNSIP YoU Og “/AtOD-CnsTUDYDAPE-ALAL Major product ‘Another 5-membered ring 7-membered ring 5-membered ring Not a major product not entropy favored more electrophilic nature of Since the keto carbon is less -CHO favors this product electrophilic Problem 2.2 (IIT JEE 2012) ‘The number of aldol reaction(s) that occurs in the given transformation is:5 iS ro OH a HCHO 8 HycX é 1H Conc. NaOH ‘OH 2 HO" 2. a4 b)3 2 at 3 ‘Answer: b g ~ = © Explanation: z 2. * Since there are 3 a-hydrogens in acetaldehyde it undergoes crossed aldol reactions with 3 moles of S. 2 formaldehyde i.c., three aldol reactions. a 4 E q z 2 OPK oy to 5 CHS — ot <— neEl— 3 H z wo? Hy 9 +0 HO, f 5 Hy GH cH ort = H 4 5 3 (oH OH (OH 3 HAC! 3 HO, Hae" © +H,0 HO, He ° HO HO Heo ‘CHG CHS 4, tH 9 ot H 4 oF (Bite H Z ont Ht +O ay & \ory 3) a & * Thus formed product (II!) contains no a-hydrogens and hence undergoes crossed Cannizzaro reaction 5 5 with formaldehyde. In this step, formaldehyde is oxidized and -CHO group of III) isreduced to CH,OH. The final product formed is also known as pentaerythritol. OH (OH i Hyco! Ho, eT 9 Conc. NaoH HO. 2 cH,-G—4 + HCHO ————» —“CH,-C—CH, + HCOONa [C2 OH HO Updates & online help through forums are only available to those who purchased this book from the author at hit ‘2oynne jo uoIssstuad oypLAL ¥¢12 ko 4h ae OH b s OH Hydrate anion Dianion ( oO ° 9 HEH + Rk — > Ht Rt + BK X_+ RH ° ° H transfer of hydride ion What are the other products possible in this reaction? * Aldoland crotonaldehyde are also formed due to self condensation of acetaldehyde. Why formaldehyde is preferentially oxidized in the final step? * The carbonyl group of formaldehyde is more electrophilic due to absence of electron withdrawing, groups and hence the initial attack of OHF occurs on formaldehyde :/Iwww.adichemistry.com’ Z E 3 & g & = E & z B z Problem 2.3 (UOH MSC 2012) ‘The most favorable product obtained in the following reaction is: ° KOH cD 9 ° 9 COH yee WO 3 pT 2 06: COH Answe LISIp YOU oq] OD AuNSIUaYOIPE-ALAL Explanation: *2,5-diketones undergo aldol condensation reactions in presence ofa strong base to give cyclized z products. Among the possible cyclizations, those result in 5 membered ring are more favored over 3 ‘membered ones. There are two acidic hydrogens on C-1 and C-6, abstraction of which lead to 5 membered rings. However the abstraction of more acidic hydrogen on C-6 carbon iskinetically more favored. CO,H COjH on Syst =n ee Problem2.4 (GATE2005) In the given reactions, identify the correct combination of their major products P and Q. [LDA=LiN@-Pr),] syne jo woysssiuuiod mnoyss yoo sip > 9° 9° LDA, THF, -78 °C LDA, THF, -78 °C gk ———+a ou PhcHO PhCHO Updates & online help through forums are only available to those who purchased this book from the author at htAnswer: B Explanation: * Above reactions are directed aldol reactions which involve preformed enolate of the carbonyl compound using strong base like LDA. The lithium enolate is treated with another carbonyl compound to achieve desired crossed aldol addition, * The lithium enolate can be either cis (Z) or trans (E). Cis enolate usually gives syn addition product and trans enolate gives anti addition product. In most of the cases, the cis form is kinetically favored and hence syn ketol is formed selectively as the major product of addition. This diastereoselectivity can be explained by the formation of cyclic six membered transition state (Zimmerman-Traxler transition state) in which the bulky group of carbonyl compound favorably takes pseudoequatorial position, whereas the bulky group on the enolate has to take pseudoaxial position. This leads to syn product, :/Iwww.adichemistry.com’ & o 3 7 3 < 3 . ¥ hay Woy Afuo opqupreav st 400g stip Jo Koo poursLI0 oy ° yo NTS © OH wa GO phan 2 ee he tau pn cis (or) Z-enolate syn (oF) erythro ketol |] resaw tBu H Ko CH Methyl group gets a Bhenyl group favors pseudoaxial position since pseudoequatorial position itis ‘cis to enolate oxygen Zimmerman-Traxler six membered ring transition state : 3 3 9 3 a 2 z z 3 g & 3 * However with cyclic systems, trans enolates are formed due to ring constraints. Hence anti addition product is formed as major product. The ring carbon must be at pseudoaxial position in the cyclic transition state. Hence the anti addition product is formed as major product. Updates & online help through forums are only available to those who purchased this book from the author at htUpdates & online help through forums are only available to those who purchased this book from the author at http://www.adichemistry.com/ 14 yo~N _ 9 ou © on LDA S onan : ae . trans (or) E-enolate anti (or) threo ketol || 108 H So / ‘0 Ph H ring carbon gets pseudoequatorial position since itis trans’ to enolate oxygen Phenyl group favors pseudoequatorial position Zimmerman-Traxler six membered ring transition state Problem3.1 (GATE2011) ‘The most appropriate set of reactions for carrying out the following conversion is: a) i) peracid; ii) 1%; iil) Zn/di, HCL b)i) Alkaline KMnO,: ii) NalO, iii) NH, / KOH ©) i) Alkaline KMnO,; ii) H’; ii) Zn/diL HCL 4)i) OY Me,S; ii) NaOEt; iii) NH, / KOH Answer: d IP JOU Og “AUIOD ALNsHUDYSIPE:ALALAYy/sdhyy WHOA, A[UO aIgeHFEAR St YOO stIp Jo Adoo peurLI0 oy ‘yoyine Jo uossstutiad mnoypar yoo styp a1N4}:/Iwww.adichemistry.conv lates & online help through forums are only available to those who purchased this book from the author at ht z U 15 Explanation on one: 0,/Me,S NaOet HO eam LH, / KOH ° Intramolecular Wott 1 Czonolysis ‘A\dol reaction Reduction * Ozonolysis cleaves double bond to give two keto groups. * Thus formed product, in presence of strong base, NaOEt, undergoes intramolecular aldol reaction {followed by dehydration to give a double bond preferably in conjugation with the keto group. + Then the remaining keto group is reduced to CH, group by WolffKishner method. The keto group is first converted to hydrazone, which loses N, upon heating with a strong base. Note: The student is encouraged to write the mechanisms of above reactions. What about other options? These too are illustrated below. COMODE Do Ray Epoxidation ae, oH ° OO=: Alk.KMnO, Nal, N,H,/ KOH a t OH ft Q f cis-hydroxyfation cleavage ecucton oo" KMnO, Pax “= cp~ dill He \ wa cis-hydroxylation rearrangement Problem 3.2 (JAM 2012) Write the appropriate structures for R, S and T in the following scheme, hy wioy Sfuo 91qujeae st y00g styp Jo doo feursi0 a4, z i g 3 9 3 a g & 2 g a & 416 : OH z 4) Tollen's reagent oo (excess) 1) BH, / THF acetone g RO g G ae ae anyon OOF (CaHe02) (CoH20) 3 i g - ‘Explanation: 2 E F 2 OH ° ° 9 BrgO. 3 gz Tollen's reagent AH o StiMoBr (CH,MgBr H eo oe 0 SS SS - Z 3g oH ‘omger ‘oMgBr E g HO. e 2 Acid catalyzed 7~ 1) BH,/ THF acetone P « =a a g dehydration 2) H0, /OH HOO Fy ‘OH ‘on Hee ‘OH XK s T Problem 4.1 (CSIR Dee 2011) ‘The major products, X & Y in the following reaction sequence are: ° A 4) NaBH, - MeOH — x & Sy ~ (Dimer) 2) TSOH ° ° a) IL b) AN 0 6 ©) X= 9 x= { ko Loy “de SO ° Answer: d E i 3 g 3 2 3 & 2 « 0 Explanation H’ Et f NaBH, 4 ( ‘TsOH oa. 150° MeOH soypne jo uoysssiuusad inoya.ss yoog sip O" 0" f ot Diels-Alder Reduction of Acid catalyzed dimerization keto group cyclization Note: TsOH is Tosylic acid. It is a strong acid. Updates & online help through forums are only available to those who purchased this book from the author at hit17 Problem 4.2 a 3 The expected product in the following reaction is: & ° © 1 equiv. MeC(OMe),, MeOH ey 8 ease neem sea 8 H H cat. TSOH ra z g 9 iene Ts0._0. z zB le Me 5 oo » gy MeO OMe 4) g e & 4 ‘OMe OMe B Answer: Z q z E § 8 = Explanation = < Hw i g bo MeO. 0. OMe Ht MeO. 0. $01, MeO 0.4 5 PAS, UY Sy Ts TO Yo I. i SN O° yo -00H » MeO O. OH — MeO. win wee My oy ‘Whaat is the role of trimethyl orthoformate? It scavenges the water formed during the reaction and produces more methanol and thus drives the forward reaction, ro™N Hq H,0> & = wd 2 3 3 gz zg a g & & z Z g é g OMe “HY ¢o*Me , ot r OH -MeOH 4 Me—(—OMe: ‘Me—X—oMe > Me—t—oMe—» we ue > Me——ome OMe OMe OMe OMe OMe I" 4 of Me <— Me—\_oMe OMe OMe Problem 4.3 OH TsCl HO ——> 7s the major product pyridine oH ots ots °. 8) TO 8) HOT yO) Answer: a Updates & online help through forums are only available to those who purchased this book from the author at ht18 Explanation i is y K ONG l2 fe} :/Iwww.adichemistry.comv 2 £ fu wiogy quo a1qujeAe st4c0g stIp Jo Adod feUTsI0 oy, * Only the primary alcohol group is tosylated. The tertiary alcoholic group does not undergo tosylation due to steric factor. * Pyridine assists in removing H" ion, ‘Now, what about the option d? This is possible when above product is treated with catalytic amounts of acid. The tosyl group is replaced by-OH group inn intramolecular S,2 reaction. -TsOH on yt om Try to explore the possibilities of attack of proton on tertiary alcoholic group. Problem 4.4 (IISC CY 2011) Prediet the major product in the following reaction. & : 4 Z 3 3 zg a g & 2 z 2 & 8 ~Aro OL 3 ° a nye DAA AA H ° 9 SL cook) cto Explanation: Updates & online help through forums are only available to those who purchased this book from the author at it19 OH \\temeraion 9° vw :/Iwww.adichemistry.comv 2 g a hy woyy Kjuo ajquyreae st-yoog sitp yo Ado yoursi10 a4, Problem 4.5 The acid catalyzed cyclization of 1,9-dihydroxydecan-5-one as given below yields a spiroketal. ‘The most predominant form of spiroketal formed will be: P-TSA, C.H,, HO. DEN PS do 9 4) Of6: Q id Answer: 4 Explanation * Simplified mechanismis shown below for the formation of spiroketal _ wap rN _, BE BQ-OR * The spiroketal will take the form given in the option | since there is double anomeric effeet which confer more stability. & g i 2 3 3 gz zg a g & & z Z g é g Double anomeric effect Updates & online help through forums are only available to those who purchased this book from the author at hit Anomeric effect: The general preference for the axial position by a electronegative group at 2nd position of tetrahydropyran systems is referred to as anomeric effect. The polar electronegative substituents prefer axial positions due to overlapping ofnon bonding HOMO cof oxygen containing a pair of electrons with LUMO of C-O bond is only possible when these MO’s are20 antiperiplanar to each other. Z 8 Note: In options 2 & 4, there is only one anomeric effect, whereas in option 3 there is no anomeric effect #2" possible. B g Problem 4.6 (GATE 2010) g 2 Eg 8 1) BH, z 3, t00¢. coo ——"*_»> g g Y 2H = 5 Me i. 8 29 2 3) aos z : Y H # 07-0 070 ‘oNo o-So z Answer: 2 = Explanation: * Diborane selectively reduces -COOH group to CH,OH, * Affer reduction, the ester group is hydrolyzed in presence of acid to give free -COOH group, which undergoes lactonization with the alcoholic group. aH, YY HW Y Et00C. COOH» Et006_A_,CH,OH ——» Hoo _cH,0H = -EtOH Me Me Me * The stereochemistry of lactonization is shown below. on i a redr eS rotate Hoon eta HOG ee H'Me Me™ ~H f OH Me~ ~H | z i g 3 9 3 a g & 2 g a & 4 Note: The trick here is to convert the staggered conformer into eclipsed before cyclization step. Ineclipsed 5 conformer, the relative configurations of methyland isopropyl groups are finalized. They are goingto be cis to each other in the eyelie product asin the eclipsed one Remember that same trick can be applied in the cyclization of open chain glucose into cyclic form. Updates & online help through forums are only available to those who purchased this book from the author at ht21 The original copy of this book is available only from Problem 5.1 2) TFAA; aq.Na,CO, 1) mCPBA > product ? CO ‘www.adichemistry.conv. Do not distribute this book without permission of author. ¢ 2 2 5% ‘o veK TS ~~ T&S 2 & of S oY 2 2 vs 3 8 fos . 8 g g 3 g e 3 = : 2 = a 2 3 eS; gia * ° ° s a - =2\¢ { a & Summa (# z= § £ i\e = g = eae : = g F a a 2 u QV oO: oO: z 3 sy 3 : E ¢ sx) 6 4 : ° 5 & qa 6 8 8 (03 3 z ee 3 a SE ECS i 3 s < g\a 2 2c o a é paroo:ansnaroysrpe:maayy:cniy ye royme arp Woy Yoo stp pasexaind oy asomp or ajquyteaL ? major product /“‘cooet CHO! " a) >) ° ° 4) ° HAcHo” Etooc A cho E1000. E1000 A oy Ss ewod i the we Answer: a Explanation: This is Corey-Chaykovski reaction. Since the sulfur ylideis stable, cyelopropanation occurs majorly through 1,4-addition route. The product isa thermodynamic one. ‘The CHO and COOEt groups get trans positions in the cyclopropane ring. This occurs since they tend to orient as far awav as possible during the evclopronanations step to avoid steric repulsion.24 2 slow oD Hp Hl H eH taaddiion \, YHA, E1000, 7 9 ‘sto NIP EE Sse 2 Fe +8 ’ “Coot irreversible /™ \ \ Cooet H €HO) __ S}L_ CHO’ COOEt groups orient Stereochemistry of €009, {Han i'space so.as to minimize cyclopropanation step Me repulsion. Hence they assume [;) "Hans postions o each other in 4 ‘cyclopropane ring. AS :/Iwww.adichemistry.comv hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, ‘Think different: What will be the product if 1,2-addition occurs? An epoxide is formed, It iskinetically favored product. But this is minor product, Why? Since 1,2-addition step is reversible, the expulsion of ylide from the intermediate is also more likely. cooet faster COCR \e lm 12edaon \ ie / — ocd s reversible’ /™ meh HO . | & i 2 g 3 9 2 : However, the 1 4-addition step is irreversible due to formation of stronger sigma C-C bond, the 3 equilibrium moves more towards 1,4 addition intermediate and the final outcome is the formation of 2 cyclopropane ring as the major product. ‘Note: But when unstable sulfur ylides are used, the major product is epoxide. Web Resource: htp:/www.adichemistry.com/organic/namedreactions/coreychaykovsky/corey-chaykovsky-1 htm! Problem 6.2 et -con lo? ° N _ el, nye -joppneyo uorssstuuod oyu O09 sm 2 7 major product Updates & online help through forums are only available to those who purchased this book from the author at it CHL, 0°C Pho Pho Pho Pho a b Q d Ae ote rote A ohe : I CH, CH, CH, CH, Answer: b25 Explanation Crotonaldehyde froms an iminium jon with Indoline-2-carboxylic acid Jiwww.adichemistry.com’ € Q = aye Oe = t, Z & E g 3 g e g & = e g g z B z The iminium and Sr ‘COZH PACO groups try ; Ny interaction with eee —— l= adjacent CH, v CH Teaction SH group during the @ 8 Son, {mation o CSc), 41,4-addition of ZH ~CHs cyclopropane ring stabilized sulfur Pr D and hence both of }S(CH), ylide and hence | them are oriented the formation of S(CHs). “trans to methyl Choon eyelopropane ing. group. ‘Nt ~soupne jo uosssiuuiod noypyas Yoo sty} aINqUSIp YoU OC HOD KxySIUIDYDIPE-ALALAY Both-CHO& PhCO groups are | cis to each other “SO Regeneration of since they tryto 2. >-cH, <— Indoline-2-carboxylic acid avoid -CH, during Os the reaction \ Ph/ Updates & online help through forums are only available to those who purchased this book from the author at http::/Iwww.adichemistry.comv Updates & online help through forums are only available to those who purchased this book from the author at ht Problem 6.3 26 (CSIR Dee 2011) ‘The correct reagents for effecting the following conversions are: ° B a) A= HCP >cHy Hye HS b) As S*CH, HC Explanation: 0 ° HC LO a Hye cH aed c (CHgl, Zn - Cu C= CHplp, Zn- Cu 9 oy HyC7P cH, Hac C= Tebbe's reagent Cyclopropanation: 1,4-addition with stabilized sulfur ylide. Epoxidation: 1,2-addition with unstable sulfur ylide. hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, & i g 3 3 zg & Z g & 2 z 4 & 227 oO ° Zn-Cu ‘Simmons-Smith reaction: + CHI, Cyclopropanation at isolated double bond. Problem 7.1 (se 2011) Z 100° + N,CHCOOEt ——> ? Ss OEt a) Cr ») Arcootr 9 AX goo¢, 4 ete S000 Answer: ¢ :/Iwww.adichemistry.conv hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, Explanation NoCHCOOEt 100 “| “N, ~ LK Dencooe SA. cooet * Heating of ethyl diazoacetate furnishes a carbene, mostly in singlet state. Generation of carbene C mn ¥\40 ° a EAM te tHe ‘oet ‘ot * Thus generated singlet carbene undergoes a concerted [1-+2] cycloaddition to a double bond to give cyclopropane ring. This step is stereospecific with respect to the geometry of double bond. However, a mixture of cis and trans forms is formed due to two different possible approaches of the carbene. Stereospecificity of cyclopropane ring formation q OEt ro > AAO H HoH & = i 2 3 3 gz zg a g & & z Z g é g Why the reaction is stopped after addition of carbene to only one double bond? * Dienes are more nucleophilic than alkenes due to presence of high energy HOMO. Hence the reaction Updates & online help through forums are only available to those who purchased this book from the author at hit28 is stopped after single carbene addition, Zz 3 Problem 7.2 2 z cooet 8 [Rh,{OAc),] 2 1 AN ee & . e gO We . 2 Po E100¢ E1000 g q S OAc & 5 a (prcroes b) er ° 3) 3 2 = g o Me Me O Me O" Me : & g Answer: d a one CJ g ‘E- Explanation: g z * The rhodium-carbenoid addition to less hindered terminal double bond furnishes a cyclopropane intermediate in which both alkene groups are cis to each other, which allows the subsequent Cope rearrangement of the divinyl cyclopropane. The rearrangement goes through the boat-shaped transition state and have the methyl and acetate groups trans to one another. ° 9° M Aco 4 Me a f Me) 3,3-cope rearrangement . ene o: ‘cooet Et00¢ Aco“ OAc Boat shaped transition state during cope rearrangement & = i 2 3 3 gz zg a g & & z Z g é g Problem 7.3 (GATE 2011) ‘The major product, X, in the following reaction sequence Updates & online help through forums are only available to those who purchased this book from the author at hit29 ° I) PTSA, Hy, OD) ete Neon Q* ———__- x N it) HO” 9 ° 9 a a) P b) i 2 fr 4) cl ‘OH al H * Anenamine of eyclopentanone is formed in the first step, which undergoes cyclopropanation reaction at double bond with dichlorocarbene that is generated by o-limination of HCl from chloroform, * This product undergoes ring expansion to furnish 2-chloroc :/Iwww.adichemistry.conv 3 3 a Z E 3 & g & = E & z B z lohex-2-en-I-one, Explanatior * Dibromocarbene, generated fiom CHBr, and base, is added to double bond to give a cyclopropane derivative that undergoes subsequent ring expansion when treated with AgNO, E q 2 0 g 2 persacd,a 4.) i z ” 5 5 z o 2 a é O 4 7 my ji) CHCl, NaOH ili) HO" cl 5 q se og) — 3 g g 2 Problem 7.4 (CSIR JUNE 2012) gS & The reagent. A required; and the major product B formed in the following reaction sequence are: 2 g z 2 Og AL br__s z 2 er z z oH oH 2 21) AS cH,Br /KOlBu & B= Br 2) A= CHyBr2/KO'Bu & B= z : 8 3 E oH oH ; 3) A CHBry/KO'BU & Br 4) A= CHBry/KO'BU & B= e 2g Answer: 3 ee 2 s g r & 5 ry & 530 CHBry + KO'Bu ——» :cBr, + KBr + 'BUOH. rg Oe Ge gs © Problem 7.5 (GATE 1991) = Type of carbenes that add to alkenes in a stereospecific cis manner are: 2A) Triplet carbenes B) Singlet carbenes both D) None 5 & Answer: B 3 g Explanation = * The singlet carbene has an electron pair in one sp* hybrid orbital. It can add to a double bond ina concerted reaction from one side. Hence it is said to show cis stereospecificity. Z E 3 & e g & = E g z B z HC. R \=/ SS ba a cD VA stereospecific concerted Rr | 1 reaction leading to cis isomer B i of cyclopropane = Singlet carbene R OR z 3 * However in triplet carbene there are two unpaired electrons; one in sp* hybrid orbital and the other & one in p-orbital, 3 When this is added to a double bond, intially a bond between doubly bonded carbon and the carbene 5 is formed, This involves pairing ofone electron fom carbene and an electron with opposite spin from the 3 double bond. Above step yields triplet intermediate, which undergoes slow spin inversion before forming the next 2 bond between alkene and carbene. This step is required before bond formation, Since the spin inversion isa slow process, there is ample time for free rotation of C-C inthe intermediate that results in scrambling of stereochemistry leading to both cis as well as trans cyclopropanes. CHy HC CHy HG, CHy Triplet carbene triplet both cis and trans intermediate cyclopropanes are formed oyine Jo uossstuod mnoyAL yoog stIp aINGUASTP 1 Problem 7.6 (GATE 2000) ‘The major product formed in the following reaction is: Updates & online help through forums are only availabe to those who purchased thisbookffom the author at ht31 Zz iC eae z = + :CH, (singlet), ———» & ‘CHs B HyC. CH, _HsC, H Hy, 4 3 ay Dee gy NSALE oy MAA D) Both A&B & . WW Ho “CH,” “CH,CHy = 2 answer: B ie : i Problem 8.1 (GATE 2011) 3 _E In the following reaction, the major product, X is: 2 2 = z 4 Ac,OINaOAc 5 g << x g 2 § a = = Fi "2 °O "OgFQ: : $ sone COCH, é Answer: © Explanation: * This reaction is called Pummerers rearrangement. It involves conversion of a sulfoxide to o~ acyloxythioether. Note: In this reaction, sulfuur is reduced and the a-carbon is oxidized. 9-977 ar-9-O% $ SCH ° <6. vw Y Problem 9.1 (CSIR Model Paper) Cab: H ? oO Oo CO,Et CO "OOK, C9 ‘CO,Et ‘CO,Et ‘CO,Et Answer: d ‘Joye Jo UOISssUad Moy Yoo stIp aINgUNSIP YoU Og “/AKOD-CnsTUUDYDAPE-ALAL Updates & online help through forums are only available to those who purchased this book from the author at hit32 Zz g Explanation ¢ ti ’ Fi Ne g Cie rue | oe x coe 8 . WV ’ a 2 7 automerization : 3 CO, Et STETTER oO & S 2 REACTION z z HO & a 4 Z 4 Attack of ylide ‘OEt é. 3 nucleophile on z : aldehyde group loss of ylide \ 8 z / ¢ 5 z i. Ni N Ne ‘ KH ‘ Codes? worse so deprotonation Ss \LA e CY ~ " Cee addition on CO,Et Skt S 7 ~o8t : * This is Stetter reaction involving 1,4-addition of aldehyde group to an c,P-unsaturated compound and 7 is catalyzed bya thiozolium salt 2 * Initial nucleophilic addition of ylide salt, which is followed by deprotonation at carbonyl carbonand 5 thus by making it nucleophilic (Umpotung). * Thus formed nucleophilic carbon adds to a, B-unsaturated ester in 1,4 manner. * Inthe final steps, the ylide salt is regenerated. ‘Think different Is 1,2-addition possible? If'so, what is the product? Yes. 1,2-addition like in Benzoin condensation is also possible. It gives a seven membered ring. Q o8t 1 \ ) OH \ oH 42 Ho S\ 9 C CoP addition S ‘OEt S ae So there isa competition between Stetter reaction and Benzoin condensation. However due to reversible nature of Benzoin condensation and more stability of 1,4-addition product, the major product is derived from 1,4-addition. soyine jo uosssiuod mnoyyar yoog stp aINgUNSTp 10U OC“) Problem 10.1 (IISc 1999) Updates & online help through forums are only available to those who purchased this book from the author at it33 2 Me, a 3 Oo + S\___ ——> Whats the major product? & cOOMe 2 3 Me py 9) 3 = ise or EB 8 cooMe cOOMe zg & answer: a zg 3 = “3 Explanation z g 3 £ SMe = 7 oH g Bom OMe b,,, OMe -B é r q" 2 ad 1 i 3 OMe Endo adduct - less stable - formed exclusively 2 3 B a z & _* It isa [442] cyclo addition and is well known as Diels-Alder reaction. It is symmetrically allowed & g : ‘g under thermal conditions. It occurs through soncerted step 3 * The endo product isa kinetic product. Its less stable than exo product. However itis formed asthe‘ -E major product since there i x-interaction possible between the diene and COOMe group and hence 3 formed faster. ef) = s Exo adduct - more stable - not major product * There is no 7-interaction during the formation of exo-adduct. Even though it is more stable than the endo product, its formation is slow. * However due to reversible nature of Diels-alder reaction, under equilibration conditions, the exo adduct may become the major product. Problem 10.2 ‘JoyINe Jo UOISSsTULIOd NoyAL YOog stIp aINGUASIp YOU OC] “AA Updates & online help through forums are only available to those who purchased this34 2 CO;CH, 4 8 BAH product e z CO,CH. CO,CH. 8 acs Hy POzCH, — S02CHa g a) ») ° 0) HCO. Ae g g z 5 5 3 Answer: a g 5 Explanation: 2 & *Itisa Diels-Alder reaction. = 8 = E 8 & a H ¢ 3 ‘CO;CH, 2 CO,;CH, * The ester group and hydrogen which are cis to each other in the reactant also maintain syn arrangement inthe product. Understanding stereochemistry Problem 10.3 (GATE 1997) The major products A & B in the following reaction sequence are: & g 2 3 3 gz zg a g & & E Z g é g Answer: 3 Explanation: * The first step is Diels-Alder reaction furnishing the endo adduct. Updates & online help through forums are only available to those who purchased this book from the author at hit35 “oH I, OH ° ir OH Endo adduct - less stable - formed exclusively * The last step involves iodo lactonization. a ==. a ws Be COOH _op—+a ° oO J) g é é ° ° ° Answer: B YY O ° Explanatior :/Iwww.adichemistry.conv * Initially, the cyclooctatetraene undergoes disrotatory electrocyelic ring closure using 6p electrons to give (1R,6S)-bicyclo[4.2.0]octa-2,4,7-triene, The two hydrogen atoms, as shown, are arranged cis to each other in above compound. H —/ TH 2) Dis rotatory thermal electrocyetic ring closure since 6x electrons are involved * Thus formed bicyclo compound reacts with maleic anhydride to give an adduct as shown below. »/ on ° Diels alder reaction : Problem 10.9 (JAM 2012) Identify the structures of X and Y in the following synthetic transformation. Updates & online help through forums are only available to those who purchased this book from the author at it Z E 3 & e g & = E & z B z ‘JoUNe Jo uo|SssTULIad joy 00g StI AINgLSIp OU OC_“;UIOD-CnSHHIOYDIPE-ALAL40 Explanation: + This transformation involves Diels-Alder reaction followed by Cheletropic reaction which eliminates sulfur dioxide to give a benzene ring. /www.adichemistry.com/ [Sy ‘ a | CO,Me CO,Me| Problem 10.10 (USC 2012) In the following Diels-Alder reaction, interaction between which of the Frontier molecular orbitals takes place? Z E 3 & g & = E & z B z $0,Tol Ph. As0,Tol + rr OC spr LK A) HOMO of diene with HOMO of dienophile B) HOMO of diene with LUMO of dienophile ©) LUMO of diene with HOMO of dienophile D) LUMO of diene with LUMO of dienophi Ph, Answer: C Explanation: * Itisan unsual case of Diels-Alder reaction in which diene is electron poor as there are electron withdrawing groups on it; and dienophileis electron rich due to propoxy group, which donates electron density through conjugation, Hence the LUMO of diene and HOMO of dienophile have smaller energy gap and can have best overlap. Note: Usually the Diels-Alder reactions occur between electron rich diene and electron poor dienophile. Therefore the best overlap occurs between HOMO of diene and LUMO of dienophile due to small energy gap. But in above case itis reverse. ‘Joie Jo uoISssHULIad Moy Yoo stIp aINgUNSIp YoU Og “/ttOD-CNsTUUDHPAPE-ALALY Updates & online help through forums are only available to those who purchased this book from the author at http:14 Problem 21.1 (CSIR Dee 2011) 2 ; 3 LAH, & pry = -70°C g ° 3 | & = APRS Ph S68) Ph 9) Phy EB 8 OH OH OH z B Answer: a & 2 Explanation: g 3 * 1,2addition with LiAIH, is more favored than I 4-addition and hence the double bond is not reduced. 5 E § & 3 [Ptr Fa 4 3 z HCH HAC. H HY HC. H “ay HC reyes ©: yo oe a SAF HO’ ph OH . 7 Tl oo HyCa cx : or =rys Ph H OH Extra information: * According to Felkin-Anh model, the transition state has staggered confirmat carbon adjacent to carbonyl group are arranged such that the large group (like Ph) isoriented perpendicular 3 to the C=O group and the medium sized group (like methyl is closer to the oxygen to avoid steric repulsion. & & = i a 8 3 9 medium small HH arm Ph large * The nucleophile attacks the carbonyl centre from the opposite side ofthe large group. According to Anh, this conformation is particularly favored due to hyperconjugative interactions between o*..., and the bond formed between carbonyl carbon and approaching nucleophile which is at about an angle of 107° (Dunitz-Buirgi angle). This is also known as antiperiplanar effect. ‘The hyperconjugative interactions stronger due to electron withdrawing nature of phenyl group that makes antibonding orbital o*, ,, ofphenyl ring, the best acceptor of electron density. Updates & online help through forums are only available to those who purchased this book from the author at hit ‘oye Jo uoIssstuad Moya yoo sp aINguAsIp15 Zz hyperconjugation 8 Burgi-Dunitz angle Nu & 107 z \ [ni Hs g py. g > ot z 8 \7 \ z £ Ph 3 4 ‘Anti periplanar effect a 2 g & Problem 21.2 (CSIR JUNE 2012) e : ‘The major products A & B formed in the following reaction sequence are: = 8 2 LAH, Sharpless epoxidation S ew ~ ——> 4 —————_ +8 g SS_LOH NaOEt L-(+)-diethyltartrate e Ae AAA ALON B ASW Anger oO 0 * propargylic aleohols are reduced to (E)-allylicaleohols with LiAIH,. This reaction proceeds through trans-hydrometallation of the triple bond leading to trans alkene upon acidic hydrolysis during workup. & = i 2 3 3 gz zg a g & & z Z g é g AIH, HO \ WoO SS ———> oye Z~ OH Son, Xd wh * Selective epoxidation of resultant allylic double bond occurs under Sharpless conditions. OH Ti(O-iPr),Me,CO,H ARAAALM ooo (#}DET, CH,Cl,, -20°C ‘0 Note: In the Sharpless epoxidation one can prediet the absolute configuration of the final epoxide based onthe following simple model. The allylic alcohol is oriented so that the double bond is written vertically with the alcoholic carbon in the lower right-hand corner. In this orientation, epoxidation in the presence of the natural L-(+)-dialkyl tartrate esters will occur from the bottom face ofthe double bond, and epoxidation in the presence of the umatural, Updates & online help through forums are only available to those who purchased this book from the author at it76 D-(-}-dialkyl tartrate will oceur from the top face. (DET OSL on eee Cot ea, are om Problem 22.1 (CSIR Dee 2011) ‘The major products A & B formed in the following reaction sequence are: OH = <_OEt Bu,SnH / AIBN ——_+a B NBS. CyHg, Reflux :/Iwww.adichemistry.com’ hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, 1) O._OEt B= Ore * Con — Co Ch hea” CR Answer: 4 } 2 Explanation: * N-bromosuceinimide isthe source of Br, inlow concentration, * Initial electrophilic attack of bromine on double bond of ethyl vinyl ether gives bromonium intermediate which undergoes nucleophilic substitution at the secondary carbon by -OH group of eyelohex-2-en-1-ol to furnish a stork bromoacetal. iB Ny Choe a Gc + ore ‘ sont cor a a eG Br tS oct H 0. ca by * The next step proceeds through fie radical mechanism to furnish 2-ethoxyoctahydro-1-benzofuran, This reaction isknown as Ueno-Stork cyclization, The mechanism of this reactionis given below. & = i 2 8 3 gz zg & z g & & z Z g é g Updates & online help through forums are only available to those who purchased this book from the author at ht7 Chain ini nn lhe — 2 ty GN tw "AIBN (2,2'-azo bisisobutyronitrile) hoy —» Ln 18 CN VM CN Chain propagation O. _LOEt O._OEt O. LOEt C Y ier oO we SY : O._OEt 0, Cer > Cort seis U,H—snBu a? :/Iwww.adichemistry.comv Z E 3 & g & = E & z B z JOYA Yoo sip aNqUSIP OU Og] “;UOs-A.nsIUIAYoIpE-ALAL Problem 22.2 ‘The major product that is formed in the following reaction is: rer Bu,SnH / AIBN GH, Reflux Reig e 2 e) 1266) 2ees | Answer: 3 Explanation: * Tributyitin hydride along with radical initiator, AIBN, reaets with organohalide to replace the halogen 2 with hydrogen atom [fa double bond is separated by four carbon atoms from that bearing halogen, then" cyclization can occur to furnish a five membered ring as described below. 2 & A fr \ -SnBu. ian ee —DO : H_COOEt EI0OC_H B ce CHO “ CHO 5 ° H 9 H g 9 pK AA coe A : H cooet 3 ‘Answer: 3 2 Explanation: zg * Aldehyde group is more electrophilic than keto group and hence is more reactive. Therefore, the © stabilized, but less reactive, phosphorus ylide selectively reacts with aldehyde part by giving an E-alkene. Problem 23.3 ‘The compound X, formed as main product in the reaction sequence shown below is: Updates & online help through forums are only available to those who purchased this book from the author at ht ‘Joye Jo UOISsstuLad OYA yooq sty)Son HOT OM Poo pnp? a a Jiwww.adichemistry.con’ 2 ° \ s ‘° \ Z & E 3 & e g & = E g & 2 B z Answer: 4 Explanation: E * The keto group is protected by ethylene glycol and the primary alcohol is oxidized to aldehyde by ‘3 using PCC. B. Thus formed aldehyde is made to react with unstable, but reactive phosphorus ylid to get Z-alkene % selectively asa kinetic product. g B Finally, the deprotection of keto group is achieved by acid hydrolysis. z a z i e i 3 A Lo 2 5 i i . Protection of deprotection of = q H’ | HOT" carbonyl group halo group 9 g g 2 S = 2 Zz a) roof PhgP2 ey i g AV H DN 4 & 2 oxidation of 1° Wittig reaction with z fs unstablized ylides to give 2 alcohol to aldehyde praia g g z 2 Problem 23.4 (GATE 1991) z © How do you carry out following conversion? 3 4 ° CHO a z g & —e 5 4 8 _E Solution: Z E__* Thisconversion can be done by following routes: g B Route-1 ‘2 *The cyclohexanone is converted to methylidenecyclohexane by treating with “ (methylene)triphenylphosphorane, which in turn is generated in situ by treating the triphenylphosphine with 8 methylbromide in presence of a base. Its followed by hydroboration oxidation reaction to furnish an & antimarkonikov’s alcohol. Finally, the primary alcohol is oxidized to aldehyde stage using PCC. Updates82 PPh, + CH,8r NaH pMso CH OH Ph a HO Oo 1) BH, in THE pce 2) NaOH, H,0, cH,cl, Route-2: * Italso involves Wittig reaction. The cyclohexanone is reacted with a Wittig reagent, Ph,P=CHOMe, which in turn is obtained by treating Ph,P°CH,OMe Ct withn-BuLi :/Iwww.adichemistry.conv Z E 3 & e g & = E & z B z 5) r DM cll OMe CF OMe n-Buti . OMe a pone | PhP +4 ——> PhyPico = ———=|PhgP*-C0 > Ph P=! 5 iv N\A oN -HCI eA, sl HH H cchaloether _phosphonium salt ylide form phosphorane form ** A Wittig reagent reacts with cyelohexnone to give an enol ether, which is hydrolyzed to generate cyclohexane carbaldehyde. * Finally the aldehyde group is reduced to primary alcoholic group with NaBH, ° ip On ePhs HOH -Ph,P=0 Ho Neo O H7 OMe Cie “MeOH Route-3: * However, the same product is formed should use s-BuLi instead of n-BuLi. Problem 24.1 (CSIR Dec 2011) In the following reaction, the product formed and the mechanism involved are: ing Me, SiCH,OMe /s-BuLias shown below. Note that we OH ‘JoUIe Jo uoIsssiUad oy Yoo StI aINgUNSIP YoU Og “/AKOD-CNsTUDYDAPE ALAC Updates & online help through forums are only available to those who purchased this book from the author at ht83 Sy NaOet N7~cl_ELOH, A ~ ~_OEt 4) Co. by addition elimination mechanism 2) Cry by benzyne mechanism NZ ~OEt N z 8 & SS ~ 2 3) L.__ by benzyne mechanism 4) Lb $2 mechanism 7 ‘NT ~OEt NN’ ~OEt 3 Answer: 1 g Explanation: * It isnucleophilic aromatic substitution reaction that occurs by addition-elimination type of mechanism, hy wioy Su 91qujeae st Y00g stIp Jo Adod feursi0 a4, S {on “oct S A dit o elimination NA~cI addition aaa N7~oEt ») * The benzyne mechanism (Elimination-Addition mechanism) can be ruled out since the base used (EtONa) isa not sufficiently strong to abstract the proton on 3rd carbon, And, moreover the attack on 2nd position can only leave the negative charge on nitrogen. Problem 24.2 (GATE 2009) ‘The major product formed in the following two steps reaction sequence is: & = i 2 3 3 gz zg a g & & z Z g é g i NO, } 2-9 — mildbase —-H,0° ‘OH Nop Pa “y Ph Ny on HINcooH “Co "Gg NO, No, Answer: A Explanation: + This reaction s the basis for Sanger’s Method of determination of N-terminal Amino acid in proteins: Inthis method, the the protein of interest is treated with 2,4-dinitrofluorobenzene under mild alkaline conditions. The fluoro group is substituted by the free amino group of the protein in an addition-eimination reaction. No peptide bond is affected. ‘Note that neither nitrogen of amide group nor oxygen of carboxylic acid group are sufficiently nucleophilic to replace the fluorine on benzene ring. The product is then subjected to acid hydrolysis to cleave the polypeptide bond (amide bond) leaving Updates & online help through forums are only available to those who purchased this book from the author at hit84 the N-terminal residue in the form ofits 2,4-dinitrobenzene derivative. This derivative can be then be = identified by chromatographic methods. :/Iwww.adichemistry.comv 3 z 3 3 E g & 5 = E g & ¢ 3 z NO, Problem 25.1 For the following allylic oxidation reaction, the appropriate statement, among the choices given below, is: Aes — AS 2 1. Suitable reagent is KMnO, and the major product is A. 2. Suitable reagent is KMnO, and the major product is B. 3. Suitable reagent is SeO, and the major product is A. 4. Suitable reagent is SeO, and the major product is A. Answer: 3 * The oxidation of dicyclopentadiene with SeO, gives the major product, A. Ittakesan unusual course of mechanismas described below. Initially, a 2+2 addition from the side of methylene bridge gives a cyclic compound which is followed by limination ofa proton from the allylic position and subsequent hydrolysis gives the final product, ‘Joye Jo uoISsstUtIad oy Yoo stIp aINgUNSIP YoU Og “/AtOD-CnsTUDYAPE ALAC 0” OH Son 242 addition Updates & online help through forums are only available to those who purchased this book from the author at ht85 [] ~~ se-on oO preferred less preferred HO OH Ho. ° O 1 MM O oo Ag Qs xvino,aci_ ne OLS = CH,Cl,, 0°C What happens with KMnO,? :/Iwww.adichemistry.conv Z E 3 & g & = E & z B z oHC ‘AcOH DD NaOAc OHC: Note: QClisa phase transfer catalyst like quatemary ammonium salt. Problem 25.2 ‘The major product formed in the following reaction is: © i) SeO,, HOAC fl) NaOH iil) HO" Hooc, PH CooH COOH , SOLS , Oe" A om Answer: B Explanation * Selenium dioxide oxidizes the -CH, group adjacent to keto group to givea diketo compound. ‘JoUNe Jo uo|SssTULIad joy 00g StI AINgLSIp OU OC_“;UIOD-CnSHHIOYDIPE-ALAL Updates & online help through forums are only available to those who purchased this book from the author at it86 HOO ‘se-oH ty ‘Se=0 Ho :/Iwww.adichemistry.comv * The diketo compound undergoes benzilic acid rearrangement in presence of base to furnisha-hydroxy carboxylic acid. The six membered ring is contracted to five membered ring during rearrangement. fy uiogy Su a1qujeae st Y00g stIp Jo Adoo feUrs0 a4, CO oO OH pe ) Loy ws EBs <2 e— Ck H,0" HO. COOH Me Problem 25.3, (GATE 1994) ‘What are the likely products formed in the following react SeO, H,0 Answer: * SeO, brings about allylic oxidation to give an allylic alcohol or conjugated carbonyl compound. z i g 3 9 3 a g & 2 g a & 4 Updates & online help through forums are only available to those who purchased this book from the author at hit‘Alder ene like 4+2 addition [2,3}-sigmatropic shitt :/Iwww.adichemistry.comv Z E 3 & e g & = E g & z B z ‘ _E Problem25.4 J The likely major product expected in the following reaction is: g 2 H 5 L pO, : 5 & > B Pee 2 i 2 ff 95% EtOH 3 Z 3 3 3 a 2 g 1) H 2) 3 = a a H CO,Et ‘CO,Et eg 3 a 4 l l & 2 ‘CHO ze 2 g 3 & gE 3) 4) H. ° = 2 4 ‘COnEt Z g ( g & OHC’ é Answer: 3 2 © Explanation: g 2 * Selenium dioxide oxidizes allylic positions of most nucleophilic double bond (trisubstituted) with E- & selectivity. No position next to the unsaturated ester is oxidized. & * Itisbecause the initial ene like 4+2 cycloaddition involves preferential attack ofthe more nuckophilic end of trisubstituted double bond at selenium, In this step, alkene uses the p-HOMO to attack the *- 3 LUMO of Se=O. Meanwhile the ~- HOMO of Se=O attacks the o*-LUMO of C-H of the allylic system. 588 ‘more nucleophilic end AA], 7% mer ie \e electrophilic end * The E-selectivity is due to cyclic nature of final [2,3] sigmatropie step in which the alkyl substituent adopts pseudoequatorial position, Se o* OH cyclic transition state of [2,3}-sigmatropic shift :/Iwww.adichemistry.com’ hy wiogy Su 91qujeae si 00g st4p Jo Kdoo feursi0 a4, Problem 26.1 Choose the final product formed in the following reaction sequence: oct 2moles ~ Nadet —+H,0" NH, a ° ° » OLUCt 2S N\-Scooet N pn 5 > OL * OE “\\cooet a Answer: 2 Explanation: * The amine undergoes double Michael addition with two moles of Ethyl acrylate to give. diester, which further undergoes Dieckmann condensation in presence of NaOEt to furnish a -keto ester. Finally the B-Keto ester is hydrolysed to corresponding acid that is decarboxylated to give the final product. z i g 3 9 3 a g & 2 g a & 4 Updates & online help through forums are only available to those who purchased this book from the author at ht89 Cee Oo S$ Oe ‘Mechanism of Michael addition: ore oo 0 Ht E100 Et0_20 Cnt QI Ow I Problem 26.2 (GATE a Zz Michael addition Michael addition e with with = ‘st molecule 2nd molecule EB oet on Et00¢ g soo ch 3 3 g e & 2 Dieckmann @ § condensation] N@CEt 2 3 COOH cooet z g Ss 2 i z 5 F 9° CX S NaOEt H,0° CS wees se ‘0 ° ma CE, oh, + “OB. Tee ‘Answer: 4 Explanation: * This is an example for Robinson annulation reaction which involves, i by intramolecular aldol condensation to produce a new ring, ial Michael addition followed z i g 3 9 3 a g & 2 g a & 4 Updates & online help through forums are only available to those who purchased this book from the author at it90 to ¢ O8t Co et LE tA : : 6 ‘0 ‘Oo 5 ” Michael addition | fo cH, U oe ‘oO coe \S> ° 9 CH, ‘Oo :/Iwww.adichemistry.comv Z E 3 & e g & = E & z B z intra molecular aldol condensation Problem 26.3 (GATE 2003) The enolate ion that reacts with 3-buten -2- one to form (Y) is: 9 cH, COL, ; oO oO O° oO ‘0 ‘O Answer: C Explanation: See the solution to previous problem. Problem 26.4 (SET MODEL PAPER) ‘The major product of the following reaction is: ‘JoUNe Jo uo|SssTULIad joy 00g StI AINgLSIp OU OC_“;UIOD-CnSHHIOYDIPE-ALAL Updates & online help through forums are only available to those who purchased this book from the author at hit1 Z 9 8 cork. i NaOEt e 8 OMe 2 g z 2 z meseaic i e & e Swe bu 3 B Answer: © 6 3 = 8 = Explanation: 2 g * Again, Robinson annulation: Michael addition followed by intra molecular aldol condensation. = * Initial abstraction of proton occurs preferentially from benzylic carbon since the earbanion generated = will be more stable. 3 * Inthe fina step, intra molecular aldol condensation, the removal of water molecule occurs such that the = double bond formed will be in conjugation with the keto group. OMe: OMe: OMe OMe OMe OMe OMe Problem 27.1 (GATE 2008) ‘The major product of the following reaction is: OL a CO,CH, ACOH, at RT ‘CO,CH, ‘CH,OH ‘CO,CH, ‘CO,CH, Answer: 3 Updates && online help through forums are only available to those who purchased this book from the author at ht i) ye ° | o = = S| % % ‘° ° ‘JOIN JO UOISSSIULIAd OYE Yoo SII aINgUNSIp Jou Og “jULODCNSTUUDYIPE'ALALA Explanation:92 * PtO, i called Adam's catalyst and is actually a precatalyst, Its reduced by hydrogen gas to platinum = black, which is actual catalyst. g * Adam’s catalyst can help in hydrogenation of double bond to single bond as wellas hydrogenation of cyclopropane ring to gem-dimethyl unit However ester group is not reduced in presence of this catalyst. Note: Very mild conditions, high activity of platinum catalyst makes this the best option for hydrogenation. However it isnot commercially cheaper. rroblem 28.1 he major products X & Y formed in the following reaction sequence are: a7 1) LDA, PhSeCi, -50°C HO, 0 ——_—_, x _""_,y re 2) LDA, Mel, -50 °C 50°C Me “SePh 1) X= Oo 0 H :/Iwww.adichemistry.com’ z 3 3 E g & 5 EB z g & ¢ 3 z & Me Me ‘SePh Me = WU seph Oe 4 lme oft a 3) X= oO Y= 04) X= oO Y= ‘0 z Choe = ie ca a: H H 8 Answer: 1 9 g Explanation: = * Initial deprotonation with LDA gives an enolate anion, which acts as nucleophile and attacks the 3, phenylselenyl chloride, which approaches from the less hindered side ic., from the side of “H’ to avoid 2 steric interaction with the ring carbon. S * However addition of LDA to above product gives planar enolate anion which is attacked by ‘Me’ 2 ‘group, again from the less hindered side to push the already present PhSe group to the side opposite to the oy Updates & online help through forums are ony availabe to those who purchased tis book from the authorat it ‘oye Jo uoIssstuad moyPLAL 4009 SI93 2 H SePh g ah, * Poot PhSe group approaches from AL ‘Oli (co the less hindered top sideiie., 2 o from the side of 'H' 8 H 2 3 2 LDA Ee 8 g g a g HH SePh_ a 5 Ca Z 2 Yoonut Mel o (of 3 a 5 & Oo z 2 Me group also approaches from the = < top Side making PhSe group to take Fa the position opposite to 'H’ 5 z * Final step involves oxidation of selenide to selenoxide using hydrogen peroxide followed by pyrolytic syn elimination to givea double bond. * The ‘H’ on the ring is anti to the selenide group and does not participate in elimination since this step 2 occurs by way of a concerted cyclic path, which requires the f-H to be eliminated is on the same side of © the selenide group (syn elimination), For this the “H’ on methyl group is readily available and undergoes elimination. HO HS Me .SePh aane 0 ee Cf po" Zhe “Phseon ‘What happens when the order of substitution with phenylselenyl and methyl groupsis changed? a H gePh Me 1) LDA, Mel, -50 °C. “Me 1,0, 0 a ———_+ ‘0 .2)LDA, PhSeC, -50°C \ 19 50°C. 0 4H 4 H * Now the ‘H’ on the ring is syn to the selenide group and does participate in the elimination. Problem 29.1 (GATE 2012) In the cyclization reaction given below, the most probable product formed is: z : g : 3 3 8 a zg g é et 2 5 Ss Ge NaH Dre GC Daa OX Answer: 3 Updates & online help through forums are only available to those who purchased this book from the author at ht Explanation::/Iwww.adichemistry.com’ Updates & online help through forums are only available to those who purchased this book from the author at it 94 * Inpresence of strong base NaH, the hydrogen on alcohol is abstracted to furnish an alkoxide ion, which attacks the carbon containing bromine. This isan intramolecular §,2 reaction and the configuration at this centre is inverted. Intramolecular $,2 Inversion at substituted site Why not the other hydroxy group participates in the reaction? Itisalso possible. However, the formation four membered ring is slower than the formation of epoxide, a three membered ring. fy wiogy Sfu0 91qujeAk stY00g stIp Jo Adod feUTsI0 a4, —~ Br Son —— U\_Lon_ slowstep Problem 29.2 (GATE 1991) ‘The product formed in the following reaction is: t-BuOOH, VO(acac), i lof a E Ss CH, A E 8 ol 2) [ 9 9) 0 4) [ 3 OH \ Go Kon \ Go 9 g Answer: 3 & Explanation: Ef * The epoxidation occurs selectively at double bond ofallylic alcoholic site. = * Ina the acetylacetonate gandin Vanadium acetylacetonate, VOfaeae) isexchanged with BuOOH 7 (TBHP) and the alcohol group of geraniol. z It is followed by coordination of second oxygen of TBHP to generate oxoperoxovanadium complex , a Z ‘metal peroxide and facilitates the facile electrophilic attack of oxygen onto the olefinic bond thatis next to 5 -OH group of geraniol. The next step involves the dissociation of the complex to give free epoxide and the vanadium complexis reused in the catalytic cycle. soypne jo uoysssiuusad inoguess95 BuOOH GU Exchange|of ligands :/Iwww.adichemistry.comv rr 20 NZ , oS 2 i 2 \ hy woyy Kjuo ajquyreae st-yoog sitp yo Ado yoursi10 a4, 9 A i ot ° =0\|| 0. 1Bu =0. | _O—1Bu 0, | 0—1Bu NP-97 1 WS Vv: Ve? Nee Ale + \ 97 SS O’ | 3) \. oS 2 co Z °. y) SX Problem 29.3, (GATE 1997) Choose the suitable reagent to carry out the following conversion, ° ° OO 1)mCPBA —_2)CF,CO,H_— 3) H,OJOH 4) 0, Answer: 3 Explanation: * The olefin part of o,-unsaturated carbonyls are electron deficient and hence can react only: nucleophilic peroxides like H,O, in basic medium. Whereas the peroxides like mCPBA, CF,CO.H are electrophilic peroxides as they contain electron withdrawing groups like nitro and trifluoromethyl. Hence these reagents cannot epoxidize enones effectively. Mechanism: & : 4 Z 3 3 zg a g & 2 z 2 & 8 Updates & online help through forums are only available to those who purchased this book from the author at it96 On) H 0-0/y>:0H =—= 0-0 + H,0 iv 9 o> ° Bey Nes O H » “dd bon Problem 29.4 (UOH MSC 2010) ‘The major product obtained upon epoxidation of the folloy acid is: Answer: C ig triene with m-chloroperbenzoic :/Iwww.adichemistry.com’ Z E 3 & g & 3 = E & z B z Explanation: * The epoxidation with mCPBA occurs at more nucleophilic double bond. In above triene the middile double bond isnot only more substituted as well as conjugated. Hence it will be more nucleophilic and is epoxidized preferentially Problem 29.5 (CSIR JUNE 2012) ‘The structure of tricyclic compound formed in the following two step reaction sequence is: a cs CHy 1) NBS (2eq,), Bz,0,, A Nn cH, -2)aq. NaOH a cl ° al Br N. ) ASS?) SS acs 4) LT (A te oH (S 9 N N’ NV Ni Answer: 4 Explanation * 2 equivalents of NBS in presence of benzoyl peroxide brominates two methyl groups on benzene. * Treatment with alkali results in a ring formation like in epoxidation. Initially, one of the bromide is displaced by OH group. Finally the rings closed by nucleophilic substitution of another bromine by this - OH group. c “cto NBS (2eq,) Bz,0,,A Problem 29.6 (GUJARAT JouNe jo uo|SsstULIad joy 400g stIp AINgLSIp OU OG “;uIOD-ENSIUKOYDIPE-ALAL a Updates & online help through forums are only available to those who purchased this book from the author at ht ET DECEMBER 2008)97 Choose the correct statements about the following bromohydrins, A & B. Z Goth Cobar é z HO. Br, g 2 . 3 _* x Ho’ = 2 8 g & 1)‘A°undergoes facile conversion into an epoxide when treated with aq. NaOH in few seconds. %- 2 2)‘B° undergoes facile conversion into an epoxide when treated with aq. NaOH in few seconds. 2 2 3)*A’can be converted to an epoxide only upon heating with aq. NaOH for 3 days. 5 * 4) Both ‘A’ & ‘B’ cannot be converted to epoxides when treated with aq. NaOH. 5 8 E Answer: I 2 3 z ion: 5 Explanation: : * Inthe stable conformer of “A’, the both -OH and -Br groups are antiperiplanar to each other. Hence the elimination of -Br is easy during epoxide formation. HO" ty Cat? O &£ es JOU OC] AUN AANSILUDYDIPE:ALALS Br A * Incase of stable conformer of ‘B’, the -OH and -Br groups are not antiperiplanar. Hence it cannot 3 undergo epoxidation easily However the elimination is possible in its less stable confirmer in which both the groups are axially 5 arranged. But the energy barrier for the interconversion between two conformers prolongs the timing of & reaction, Hy oH oHs CoHi7 cn Br: — Hay Ho! ca B . é Hy stable conformer less stable conformer No elimination possible Elimination is possible Problem 29.7 (CSIR JUNE 2012) ‘The major product formed in the following reaction sequence CO 1) mCPBA OH OH oO ° Answer: 4 Updates & online help through forums are only available to those who purchased this book from the author at ht ‘ZOYINE JO UOISssIULIAd joULA yoog StI INGE Explanation: * mCPBA epoxisize the double bond. * The epoxide is opened in presence of Lewis acid, BF, such that a stable benzylic carbocation is98 formed, which is followed by loss of proton, Final workup hydrolyzes OBF, to give an enol that tautomerizes to keto group. L\ 6 BF \ {e eu -HF CO 0-BF 2 workup oor Problem 30.1 (GATE 2012) ‘The product from the following reaction is: :/iwww.adichemistry.com’ hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, Cola ‘Aco Explanation: * Ibis Barton Reaction involving the photolysis ofa nitrite to formaé-nitroso alcohol. The nitroso group tautomerizes to oxime. The five radical abstraction of H?’ from -carbon involves a cyclic six membered ring transition state. Inabove compound, a steroidal compound, the abstraction of “H’ from methyl groupsat either C-18 or C-19 are equally possible. In the following mechanism, abstraction fromC-18 is shown. & = i 2 3 3 gz zg a g & & z Z g é g Updates & online help through forums are only available to those who purchased this book from the author at hit99 Zz ° HOC, 3 N 18 q 19, OS GH on GH E CH CH 5 ACO. ‘AcO. 2 3 2 Ee : | O=N> bh es z Ee BQ ye 4 oN*CH, OHH,C" OH CH, @ 5 CHy CH; CH, 2 3B Aco. AcO. ACO. e 3 8 3 & Problem 30.2 (GATE 2010) g ‘The major product in the following reaction sequence is: z Me, Me i) NOCUPy ii) light “OH ili) hydrolysis Answer: C Explanation: * The nitrite formed, after treating the alcohol with Nitrosyl chloride, undergoes Barton reaction upon exposing to light. The y-methyl group is activated to ~CH,-NO ina cyclic transition state. The -CH,-NO tautomerizes to give an oxime group -CH=NOH. ‘The oxime is finally hydrolysed to aldehyde group. & g 2 3 3 gz zg a g & & E Z g é g Updates & online help through forums are only available to those who purchased this book from the author at hit100 The original copy of this book is available only from ‘www.adichemistry.conv. Do not distribute this book without permission of author. = & = 5 = = . LE K So ‘2-5 z <—_ <> ° =3 z z 5 8 5 5 3 zg § 2 2 2 3 5 | 3 g 3 SA 9 3. 3M s 3 § g x = s Oo g 7 4 sf & 4 a A 27 5 ¢ Ss O fi 2 2 3 bos & & X ‘ n 2 ‘: ‘: xz A So OQ. O/ ee zo xz (250 roa Kystuaypipe aay /sdny ye JoMne axp toss YOOg StI paseyamnd oy asoyy o} aIgeteae suo are sumUOF YNop day sumo 7p sarepdA,127 Problem 41.1 ‘What is the major product in the following reaction? A Br, ~ dark * The ring opening occurs such that a more stable secondary carbocationis formed and bromine prefers to attack from the less hindered side of the ring. This reaction isnot stereospecific. A mixture of diastereomers are formed, 3 er zB br Br. of Bw 8 Q) D 2 sv ) ay A oe § 0 Br Br Answer: A 3 E Explanation: Z E 3 & g & EB z & z : Problem 41.2 Bro ion of (E) -2- butenedioie acid giv a) (2R,38)-2, 3-dibromosuceinic acid b) 2R, 3R)-2, 3- dibromosuceinic acid ¢) a mixture of (2R, 3R)- and (28,3) 4) 28,38)-2, 3-dibromosuecinie acid Answer: a -dibromosuccinic acid Explanation: * Ameso compound, (2R,38)-2, 3-dibromoscuccinic acid is formed in the bromination as illustrated below. Attack of Br’ onto double bond may occur from above or below. However the bromonium ions, formed are one and same. Again two possible attacks of Br are show compound. us final brominated product formed is a meso Joye Jo uoISssHULIad Moy Yoo stIp aINgUNSIp YoU Og “/AtOD-CNsTUUDHDIPE-ALALY Updates & online help through forums are only available to those who purchased this book from the author at hit128 H3C._,COOH soar Ler 2 fea 2 HyC. — XE BF — HOOC™ RCH, 4 BrxBry HyC.,, COOH — > ay, "Br Hooc* ~cH, Hse COoR\. 6 + srl BF Jiwww.adichemistry.com’ z 8 = 8 3 g & Z E 3 & g & EB z & z : HOC” RCHay HjC. COOH p Ua “Ler Hooc™ CH, Problem 41.3 (GATE 2222) HOO, Br, = — +x p COOH HOOG _ COOH BE, Q ‘The correct statements with respect to above pair of reactions are that: i) The reactions are stereospecific ii) X is erythro and Y is threo isomer iii) X is threo and Vis erythro isomer iv) each of Pand Q gives a mixture of X and Y Options: AISI B)i& ii Oisiv D) = Answer: A Joye Jo uoISssHULIad Moy Yoo stIp aINgUNSIp YoU Og “/AtOD-CNsTUUDHDIPE-ALALY Explanation: * Bromination of double bond in fumaric acid, trans isomer gives only an optically inactive erythro compound, whereas maleic acid, a cis isomer furnishes optically active threo compound. A racemic mixture is possible in case of threo compound due to equal probability of attack ofbromine from either sides of the double bond. * Since each reaction leads to formation of only one kind of isomer ie. threo or erythro, these reactions are said to be stereospecific reactions. Updates & online help through forums are only available to those who purchased this book from the author at http:129 noon, — ‘Bee i Z E 3 & g & = E & z B z = HOO“ KH Es Nea g 3 3 E COOH s > er fre § ~ Hooc*“H OR HA COORN, LL, a] Bh Hooc“ RH A _ R s ‘JoUNe Jo uo|SssTULIad joy 00g StI AINgLSIp OU OC_“;UIOD-CnSHHIOYDIPE-ALAL Problem 42.1 (GATE 2000) Oxymercuration-demercuration reaction of 1-methyleyclohexene gives: a) cis-2-methyleycloxanol_b) trans-2-methyleyclohexanol Updates & online help through forums are only available to those who purchased this book from the author at ht130 ¢) I-methyleyelohexanol _ d) mixture of cis and trans-2-methyleyelohexanol Answer: ¢ Explanation: * The attack of water occurs at more substituted carbon and hence the alcohol is formed according to Markonikov’s rule, * Inthe mercuration step, the -OH and the mercury acetate groups are antito each other. NaBH, :/Iwww.adichemistry.comv Z E 3 & g & = E & z B z Problem 43.1 (GATE 2000) Pyridine undergoes electrophilic nitration at elevated temperatures to give the following as a major product: NO, YY No, 2 NZ N* NO, 7 NO, Answer: Explanation: * Pyridine does not undergo electrophilic substitution easily at carbon atoms ofthe ring, since itis converted to pyridinium cation in the medium containing electrophilic species. The positively charged pyridinium cation is many orders of magnitude less easily attacked by the electrophile. Hence nitration of pyridine, even under elevated temperatures, is highly difficult and the yields are very poor (about 6%). Usually the electrophile substitution occurs at the B-position, since the a. & 7 positions are electron poor inpyridinium cation. oO KNO,, cone. H,S0, oO 7 300°C Nm —— O Sy SS No," ( Roy NOz o_o Cy ® fi + N Resonance forms of pyridinium cation ‘JoUNe jo uo|SsstULIad joy 400g stIP AINgLSIp YOU OC_“;UIOD-CNSHUIOYDIPE-ALAL N’ N i i b , 4 H H 4 Problem 43.2 (CSIR JUNE 2012) ‘The major products A & B formed in the following reaction sequence are: Updates & online help through forums are only available to those who purchased this book from the author at itUpdates & online help through forums are only available to those who purchased this book from the author at http://www.adichemistry.com/ 131 y NaH PhCHO —> AB Nn PTSA, A H 4) A= { “C5 om cdre Be « N N N H HO Pee H a Ph oe Cobos \ omnes a a aaa i Non NI Answer: 4 ul Ph a WY Explanatio * N-alkylation of indole occurs in presence of strong base, NaH as it contains Na’ ion. * The N-alkyl indole derivative is treated with benzaldehyde in presence of PTSA to furnish a 3,4- dinydro-1H-{1 4]oxazino[4,3-a]indole derivative, ro [o% HY Son Ph Problem 43.3, (SET MODEL PAPER) ‘The major products A & B formed in the following reaction sequence are: (CH,),NH i) Me,SO, \ > a > 8 N’ HCHO, ACOH ji) NaCN, 70°C. " / N. \ N 4 7" oN 3) A= \ ‘od N N Answeri2 H IP JOU Og “UO AnysIUOYSIPE:ALALAYydhyy WHOA, A[UO aIgeHEAL St YOO stIp Jo Adoo peurLI0 oy ‘yoyine Jo uossstutiad mnoypar yoo styp a1N4}132 Explanation * Mannich reaction on indole furnishes Gramine. Its then treated with dimethyl sulfate to givea quaternary ammonium salt, which undergoes elimination and subsequent attack of cyanide ion to give 1H-indol-3-ylacetonitrle Zz 3 z 4 2 H of 4 oy HO | aH ia g 5 iy ka “a y =z ee, NH NY =a Ne = BK ey Mo, 5 5 iminium ion zg 5 3 3 Hen E Eco. : 3S N N Ef i i 3 z Problem 43.4 (GATE 1991) Propose a suitable mechanism for the following reaction, NH2_KNH, / lig. NH, ‘Br Mechanism: * This reaction is initiated by abstraction of an acidic hydrogen from amino group by a very strong base potassium amide. Itis immediately followed by electrophilic attack ofhydrogen and subsequent breaking ofring and making of pyrrole ring. . pl Sh Br EN BN Sih Problem 44.1 (GATE 2001) & g 2 3 3 gz zg a g & & E Z g é g ‘The major product formed during the hydroboration-oxidation of 1-methyleyclopenteneis: HO, A) A on 8) 3 ° Kf 0 Ao Answer: D Explanation Updates & online help through forums are only available to those who purchased this book from the author at hit133 * Hydroboration of alkene with diborane involves syn addition of B-H to the double bond H : 2 Moles db BH, P oO [t}- bee a i. ‘Three moles of alkene reacts with one mole of BH, to forman organoborane, which is oxidized to a borate upon reacting with H,O, / NaOH. This gives alcohol upon hydrolysis. :/Iwww.adichemistry.conv hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, 3H,0 OH J T .OH + XO) Ho-P-on * Inhydroboration-oxidation method, anti Markonikov alcohol is formed. * The spatial relation between -CH, and -OH groups in the final product is trans to each other. Problem 44.2 Hydroboration of 1- methyleyclopentene using B,D,, followed by treatment with alkaline hydrogen peroxide, oe A) 8) +p °) on D) ey |-o% a Ao a Answe Explanation: * Hydroboration of alkene with B,D, involves syn addition of B-D to the double bond. In the final oxidation step, the -OH group is formed. Its orientation is syn to the D atom on adjacent carbon, & = i 2 3 3 gz zg a g & & E Z g é g Updates & online help through forums are only available to those who purchased this book from the author at hit134 ftolos Po \ Obes Ooo Cyan 2050 20-04 a 8. 2-OH D i D, x my cen 3H,O :/Iwww.adichemistry.com’ Problem 44.3 (GATE 2010) In the following reaction the major product formed is: BH, CO,Et CO,H_| > hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, y iy Answer: B Explanation: * Diborane selectively reduces carboxylic group to primary alcohol leaving ester group intact. Hydrolysis of resultant product finally gives a lactone, ‘we BH. Me Ht Me, a ter 10,c._ co, Me -£t0H HO. E10,C COOH E10,C CH,OH oP Ho [eo ve & g 2 3 3 gz zg a g & & E Z g é g Note: Initially, the carboxylic acid reacts with diborane by liberating hydrogen gas and gives a triacylborate. Problem 44.4 (CSIR JUNE 2012) ‘The major product, B formed in the reaction sequence given below exhibited a carbonyl Updates & online help through forums are only available to those who purchased this book from the author at hit135 absorption band at 1770 cm" in the IR spectrum. The structures A and B are: Answer: 2 :/Iwww.adichemistry.comv hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, Explanation: * The hydroboration of diene with 9-BBN followed by oxidation with peroxide gives an alcohol. Since the end orbitals of HOMO of diene have larger coefficients, they will interact efficiently with the LUMO of boron. Hence the boron part of 9-BBN attaches itself to end carbon of diene. Due to bulky nature of 9-BBN, it must approach from the opposite face of methy acetate substituent on the next carbon. .COOMe COOMe cooly COOMe oe orf oo on BR, | H pe .COOMe 9-BBN “OH ae I * During the conversion of A to B, a lactone, by treating with Mesityl chloride, MsCl, involves inversion of configuration at alcoholic carbon. & = i 2 3 3 gz zg a g & & z Z g é g Mesityl choride a) ) Updates & online help through forums are only available to those who purchased this book from the author at ht Problem 44.5 (GATE 2012)136 The original copy of this book is available only from é 3 £ 3 z 2 g 2 zs e 2 2|5 @ € S|5 £ s]/- = eee eee 3 fo} = alc & 2 22 zB als : \ Sida = < <* ¢@ muoo Kysnuraypmpe mau vww.adichemistry.com/. Do not distribute this book without permisssion of author, Me _Redraw —=— ho. OH (GATE 2005) ‘The major product in the following reaction is: Me Redraw z a ce iy ye.zoyme atp LOY O09 stp paseyound oy asoup OF a]quTTEAe uO axe suuTUg} YSNoIKA doy auIU0 7p sawepdn) Problem 45.1137 x Li ig.NH, {BuOH ott Bu ° x ° dx: » by ° cy 'NH2 ‘O-t-Bu Answer: C ‘Explanation: * Lithium very easily loses its valence electron that is solvated by ammonia. These solvated electrons participate in the reduction of enone. * Initial transfer of an electron to enone forms a radical anion that is protonated by the alcohol to form radical, A second electron transfer forms an anion that can undergo tautomerization to an enolate. It azives saturated ketone upon final workup. :/Iwww.adichemistry.com’ hy wiogy {uo a1qujeae st y00g st4p Jo Adod euro a4, ANH, + uy OMB Ut + ete, os electron ° oc e INH), rsson t-BuOH ome Oc protic Hworkup unsaturated enone radical anion enolate solu Note: The enolate can be alkylated at o-position by using any alkylating agent like alkyl halide, The a- carbon containing the double bond is only alkylated. It is an example of regioselectivity. oO Oo . ‘ Problem 45.2, (GATE 1991) ‘The reduction of but-2-yne to trans-but-2-ene can be brought about by: A)H,/PtO, B)Lindlarcatalyst C)LiAIH, — D) Li/ liquid NH, Answer: D Explanation: & = i 2 3 3 gz zg a g & & E Z g é g * PtO, is called Adam’s catalyst and is reduced to Pt with H, during reduction reactions. (That means, PtO,/H, is equivalent to Pt/ H,). Itreduces triple bond to single bond. No control. It is not possible to stop the reduction at double bond stage. B PIO, +H, NS * In presence of Lindlar’s catalyst (Pd / BaSO, in quinoline) reduces triple bond to double bond. However the addition of hydrogens is syn and the product will be cis-2—-butene. Updates & online help through forums are only available to those who purchased this book from the author at hit138 Pd + Hyp ——___» BaSO,-Quinoline 4 jo9 jeursi10 a4 The activity of Pd catalyst can be reduced by adding catalytic poisons like CaCO,, BaSO, ete., to control the hydrogenation, Pd is precipitated on CaCO, or BaSO, and treated with lead({II)acetate and quinoline. This modified catalyst is also called Lindlar’s catalyst. 3409 spo: * LiAIH, cannot reduce non polar bonds. * However, dissolving metal reductions using Li / liq. NH, yields cis-2-butene due to anti addition of = 8 & “2: hydrogens to double bond. g 3 Li/ lig. NH, e Hy \ = : : H é “= Anti addition ofhydrogens to triple bond is best achieved by alkali metals in liquid ammonia, It results in only partial reduction to double bond and further reduction to single bond is not possible. 5 : 2 Na-lig.NH, R H Rt 2 ig. NH, tBuoH =H OR® Alkali metals can lose electrons from their outer shell very easly, These electrons are actually solvated in liquid ammonia by giving blue to bronze color to the solutions. Mechanisi Sodium donates an electron to alkyne by giving an anion radical, which abstracts proton from the solution and givesa vinyl radical. Then sodium donates second electron to this vinyl radical to give an anion that adopts stable trans geometry. Finally, this anion abstracts another proton to give selectively an E-alkene. @ N 4 2 2QIH BuOH H le 2 2°. 2 BUH R WY Re —> nO Tae we 1 this anion eae trans geometry * Partial reduction of terminal alkynes by this method normally fails as the alkyne reacts to givethe &: alkynyl sodium salts (like sodium acetylide), which resists reduction because of the negative charge on the alkynyl carbon atom. In the presence of ammonium sulfate, however, the terminal alkyne is preservedand "3 & : 8 8 3 3 z a g & 2 g reduction gives the terminal alkene. 3 * Alcohols like -BuOH act as proton donors and prevent the accumulation of strongly basic amide ions. 7 2 Problem 45.3, (CSIR OLD MODEL PAPER) & ‘The reagent suitable for converting oct-4-yne to trans-oct-4-ene is: 2 1)H,-Pac 2)Pd/CaCO,/H, 3) NaBH, 4) Na /liq, z Answer: 4 Explanatio * Both Na/ lig. NH, and Pd/ CaCO,/ H, can hydrogenate triple bond to double bond only (controlled hydrogenation). Updates online ep trough forumsare only avaiable to those who purchased thisbook ome uhor at i139 * Hydrogenation with Na /lig.NH, isan ‘ant’ addition and gives trans-alkenes. Na-lig.NH, _ H = —_—_—> Anti addition H trans-oct-3-ene oct-3-yne or (BE}oct-3-ene * Whereas hydrogenation using Pd/ CaCO,/ isa ‘syn’ addition and gives cis-alkene, Pd-CaCO,-H, HH => — aaa ‘Syn addition cis-oct-3-ene, :/Iwww.adichemistry.com/ oct-3-yne Z E 3 & g & EB z & z : or, (32}-oct3-ene Problem 45.4 Reactant P gives products Q and/or R. 4 H 0. — |] Zoe “AY ri 4 Q R Pp The possible reagents are: (1) 2Na / liq. NH, (II) H, / Pd / CaCO, (quinoline) & (111) H, / Pd/C ‘The correct statement with respect to above conversions is: A) Qis obtained on treatement with reagent (I). B) Rand Q are obtained on treatment with reagent (III). © Ris obtained on treatment with reagent (I). D) Ris obtained on treatment with reagent (I). Answer: C Explanation: Refer previous problems. Problem 46.1 (GATE 2004) Cyclohexyl benzyl ether when reacted with hydrogen in the presence of 10% palladium on charcoal generates a mixture of a) cyclohexanol and benzyl alcohol b) cyclohexane and benzyl alcohol ©) cyclohexanol and toluene 4) cyclohexane and toluene -JoUINe Jo UoISssHUIad Moy Yoo stIp aINgUNSIp YoU Og “/ttOD-CNsTUUDYPAPE ALA Answer: ¢ Explanation: * O-benzyl and N-benzyl groups can be removed by hydrogenolysis using 5-20% Pd catalyst. Its high activity and low tendency for reduction of aromatic rings qualifies it as a choice for carrying out debenzylation. Updates & online help through forums are only available to those who purchased this book from the author at hit140 —* Oh ons LQ 10% PdlC ° Problem 46.2 (CSIR JUNE 2012) Among the following, the compound that undergoes deprotection easily on treatment with hydrogen in presence of 10% Pd/C to generate RNH, is: 1) 3) 9° 4) 9 2 9 ° rao "aainn” Mahon “aon ‘Answer: 3 CS Explanation: * The carbamates undergo hydrogenolysis with H, in presence of Pd/C to give amines along with carbondioxide and a hydrocarbon, :/Iwww.adichemistry.conv Z E 3 & g & = E & z B z ° lr ie | —> R-NH, +O, 14 OH unstable carbamie acid Ra Me NH O° — > + 10% Palc ne) * The ease of hydrogenolysis increases with increase in the positive charge on heteroatom like oxygen. Hence the benzyloxycarbonyl group, Cbz undergoes ready deprotection under these conditions Among the given options containing the 4th option can be ruled out due to steric factors. It reacts slowly. Problem 47.1 (GATE 2010) The major product in the following reaction is: ‘JoUNe Jo uo|SssTULIad joy 00g StI AINgLSIp OU OC_“;UIOD-CnSHHIOYDIPE-ALAL Explanat * Diazotization of trans-2-aminocyclohexanol by nitrous acid followed by deamination results in ring contraction to give cycopentanecarbaldehyde. * The diequatorial chair conformer of diazo compound is more populated and the only bond that is antiperiplanar to the diazo group, in this conformer, is the ring bond. Hence the ring contraction occurs by rearrangement of this ring bond on to the developing carbocation at the time of elimination of diazo group. Updates & online help through forums are only available to those who purchased this book from the author at hitopmategt 4. Note: However, both ring contraction and hydride migaration are observed during deamination of cis- 2-cyclohexanol since two conformers with same energy are possible. (rt LG, 2 bn © or TAX H Two conformers with equivalent energy :/Iwww.adichemistry.comv Z E 3 & g & = E & z B z Problem 48.1 (UOH MSC 2010) ‘The major product obtained in the following transformation is: oO As § chon a OH 9° Oo H Ayn a Bron A yoo ons ty Oo oO oO Answer: A Explanation * It is Intra molecular Cannizzaro reaction, The aldehyde group undergoes oxidation and the keto group is reduced to alcohol { - \e OH Dyn (oe oH not NY Ayes proc on 6 workup Note: However, aldol products are also formed in above reaction. Problem 49.1 (UOH MSC 2010) The major product obtained in the fol ‘JoUNe Jo uo|SsstULIad jnoypA 400g stIp AINgLSIp OU OC_“;UIOD-CnSHHIOYDIPE-ALAL Updates & online help through forums are only available to those who purchased this book from the author at ht142 co OCH, (CH,),Cl CO ~ OT ™ Acc Answer: C Explanation * The positions: 1, 8 ,6, 10 and 3 have more electron density in 2-methoxynaphthalene due to +M. electron donating nature of methoxy group. :/Iwww.adichemistry.conv A 1rA8 = yee OCH, OS OCH, OCH, OCH, CE Cre Uo N hy wiogy Stu 91qujeae st Y00g stIp Jo Adod feurs0 a4, * However, substitutions at the positions 1, 3 & 8 can be ruled out, as such, they are sterically not favored. Substitution at 10th carbon is also not easy since itis a bridge head carbon and sterically more demanding. * Hence the major product is 6-tert-butyl-2-methoxy naphthalene as illustrated below. Resonance structures (H3C)3C° (H3C)3C" : 3 3 9 3 a 2 z z 3 g & 3 Updates & online help through forums are only available to those who purchased this book from the author at hit Problem 50.1 (UOH MSC 2010) ‘The product obtained in the following transformation is143 CO,CHs a " pp CHLOH oy © c0,cH, CHO CHO CH,OH A) B) c) D) oy OH OH Answer: A oO /www.adichemistry.com/ : ; bee ; Explanation: * Sodium borohydride can selectively reduces keto group to alcohol. It cannot reduce esters, amides and acids. hy wioyy Su 91qujeae st y009 styp Jo Adoo feursi0 a4, Problem 50.2 (SC 2009) ‘The major product in the following reaction is: ‘ee NaBH,, CeCl, N’ OCHS CH,Cl,, MeOH Ga -78°C A) OH B) ° ©) ALOH D) OH Cen. Cer elena Sex. H Sen Non Mn Answer: C Explanation: * Sodium borohydride in presence of CeCl, selectively reduces a,b-unsaturated carbonyl compounds into allylic alcohols. It is called Luche’s reduction. * The selective 1,2 addition is facilitated by strongly oxophilic Ce" ion which coors carbonyl oxygen, * Inthe present case, the attack of borohydride occurs from the opposite face of adjacent CHOCH, group due to interaction of Ce” with not only carbonyl oxygen and also with methoxy group. tes to the & = i 2 3 3 gz zg a g & & z Z g é g ZVOH pp NZ oe px NSH NON OCHS aaa . t { H—BH, Updates & online help through forums are only available to those who purchased this book from the author at http:41 Problem 11.1 (CSIR Dee 2011) ‘The major products A & B in the following reaction sequence are: :/Iwww.adichemistry.comv hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, Explanation: * The inital step isa thermal electrocyelic ring opening reaction involving ‘con’ rotation to givea diene. C= © R= CL electrocyclic ring opening by con rotation under thermal conditions ‘The orbital picture of con rotation is shown below. & i 2 8 3 9 3 a g & a carlton E 3 Note: The diene system formed in the electrocyclic ring opening reaction contains 4r electrons and hence the ring opening step involves ‘con’ rotation under thermal conditions. S According to Woodward Hoffinann rules, the total number of (4q + 2), and (4r), components is odd & (0+1=1)when the rotation is ‘con’. Hence under thermal conditions, the ring opening occurs by ‘con” mode. Again we have to count the number of x electrons in the open system. * The last reaction is Diels alder reaction of the diene moeity with a dienophile, maleic anhydride furnishing kinetically favored endo adduct as major product. ums are only available to those who purchased this book from the author at htt SSS jouNe JO UO! Updates & online help throu:Updates & online help through forums are only available to those who purchased this book from the author at http:/www.adichemistry.com/ 42 Problem 11.2 (CSIR JUNE 2012) ‘The product formed in the following concerted reaction is: Wy wio4} Afuo IquPEAR st 4009 sty Jo Ado jeuNsLI0 a4, 4 4 H H H Answer: 1 Explanation: * This is an electrocyelic reaction involving 6x electrons, Hence the ring closure occurs by dis rotation & and the bridge hydrogens in the resultant product are cis to each other. Ob = 2 2 & g F a 8 3 2 g & 4 (dis rotation) Problem 11.3 (CSIR June 2012) ‘The two step conversion of 7-dehydrocholesterol to vitamin-D, proceeds through: bP ee Y 1) photochemical electrocyclic disrotatory ring opening; & thermal antarafacial [1,7] H-s 2) photochemical electrocyclic conrotatory ring opening; & thermal antarafacial [1,7] H-shift. 3) thermal electrocyclic conrotatory ring opening; & photochemical suprafacial [1,7] H-shift. = 4) thermal electroeyelie disrotatory ring opening; & thermal suprafacial [1,7] H-shift. Jo uoJsssiutad nog yoog sty) 23n} Answer: 2 Explanation:43 hy CH, eS a Ly conrotatory electrocyclic ring opening antarafacial (1,7] H-shift 6x electron system 8x electron system allowed under photochemical conditions allowed under thermal conditions intarafacial 4,7 H-shift electrocyclic con rotation a — Zoe [yee LHP -# — [xcH, — pore A e E Problem 11.4 (GATE 1991) ‘The type of reaction and conditions under which the following pericyclic reaction takes place are: A) electrocyclic ring opening & photochemical B) electrocyclic ring closing & thermal ©) [2,2] eyeloreversion & thermal D) [2,2]-cycloreversion & photochemical :/Iwww.adichemistry.comv Z E 3 & g & = E & z B z Answer: Explanation: * It is an electrocyclic ring opening reaction involoving 4t-clectrons in the transition state. Hence it can open by con rotation under photochemical conditions to give a open diene system. —/ 7] Con rotation possible under photochemical conditions for 4nx system * Under thermal conditions also the ring opening is also possible but the mode of opening will be by disrotation, Problem 11.5 ‘The conditions and type of reaction for the following conversion can be best described a: OH OH OO OH OH 1) Photochemical 8r disrotatory electrocyclic reaction 2) Photochemical 8r conrotatory electrocyclic reaction ‘JoUNe Jo uo|SssTULIad joy 00g StI AINgLSIp OU OC_“;UIOD-CnSHHIOYDIPE-ALAL Updates & online help through forums are only available to those who purchased this book from the author at ht44 3) Thermal 8n disrotatory electrocyclic reaction 4) Thermal 8x conrotatory electrocyelic reaction Answer: 4 Explanation: * It isa conrotatory electrocyclic reaction, For 4n system, electrocyclic con rotation occurs under thermal conditions. Note: Inabove diagram, the delocalization of'x electons is not shown. The arrows are representing only con rotation of bonds. :/Iwww.adichemistry.conv Z E 3 & g & = E & z B z + [5,5] sigmatropic rearrangements are thermally allowed and occurs through supra faci orbitals Problem 12.2 (GATE 2009) In the reaction: £ z & Problem 12.1 (CSIR Dee 2011) The product formed and the process involved in the following reaction is: z OK & é S _4 g 3 Z z 2 2 a ° ° g 3 a 1,5-sigmatropic °) “S _ 3,3-sigmatropic = 2 rearrangement 2 rearrangement 9 g g z 8 OK & z ») 5,5-sigmatropic a SS 1,3-sigmatropic 2 3 rearrangement Z_ ‘arrangement 5 & Answer: b : z z zg z 2 os z 2 ya ok Ht 9 3 : SOY 4 Z 5 Leo, g é Bee g 3 S 2 * Thisis anionic oxycope rearrangement type of reaction, es B® Thesigma bond is migrated from carbons | & 1" to carbons 5 & 5* positions. 5 S teractionof © i: 2 5 7 & 545 a OL. A a co q > x+y where * = "C labelled carbon 3 Nw & the major products, X & Y are respectively: E g 3 OH .OH .OH OH os 5 NAS NOY i 5 4 oH OH OH Ong pOntnaoO ~GQyn0 | 3 a SS Ee "2 answer: 2 = g g & © Explanation: 5 Its laisen rearrangement involving [3,3]-sigmatropic rearrangement of phenylally ether to give both & ortho and para substituted phenols as shown below. The para product is formed after two consecutive = _E [3.3}sigmatropie rearrangements, i wei i 2 ee 2 e E 5 ~, z $ Ona A 0 x a 8 9 z & ~ 2 2 | redraw =O § 3 3,3-sigmatropic —_ — I > a Claisen rearrangement 9 g g e 3,3-sigmatropic & 2 Claisen rearrangement g a ge = Problem 12.3 (GATE 2004) & _E The product X formed in the following three steps reaction z 2 z = 1) LDA, TMSCI z 3 2) 150°C x z 5 “0 3) HO" 3 : i Oe Sonn 1 4 2 g + 0 2 Ey 2 E answer: 4 5 S g 2 .& Explanation: : E _* Abstraction ofprotonfroma-methyl groupofesterby LDAand subsequent treatment with Trimethysi ] chloride, TMSCI results in the formation of a cyclohexenyl sly! ketene acetal, which further undergoes = Ireland-Claisen rearrangement upon heating. Treland-Claisen rearrangement isa [3,3]-sigmatropic reaction, a variation of Claisen rearrangement,46 Final step is removal of silyl group by acid hydrolysis to get free acid. Sp A, [ios . nol ao FS ou 4S ond" 929, on Ireland-Claisen rearrangement ‘TMSC! = Trimethylsilyl chloride, (CH,),SiCI :/Iwww.adichemistry.comv Z & E 3 & e g & = E g & z B z * The stereochemistry of Ireland-Claisen rearrangement is shown below. It occurs viaa boat transition state. oTms OTMS oTMS Problem 12.4 (GATE 2011) yy ym yy ye O Me O Me Oo & O & Answer: a Explanation: * It isan example of Corroll rearrangement, in which a B-keto allyl ester is converted to 7,-unsaturated ketone. It involves initial [3,3]-sigmatropic rearrangement, akin to Claisen rearrangement, of enol form of - keto allylester to give a B-keto-y,6-allyl carboxylic acid, which undergoes subsequent decarboxylation. Oo 0 oO Ho Oo eo OH O Oo AA, AA, Fo GLA we Et Za A> et Are [3,3]. Tautomerization _sigmatropic decarboxylation reaction ‘JoUINe JO UOISSsIULIad oy Yoo stIp aINgUNsIp roU Og “/AtOD’CnsTUDYDAPE-ALALY Updates & online help through forums are only available to those who purchased this book from the author at ht ‘Think different:47 Why not the reaction occurs in a coneerted step? Oo ° ole) % Problem 12.5 (GATE 2005) ‘The major product in the following reaction is: OH KH, THF ) 4 :/Iwww.adichemistry.com’ hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, Explanation: * Itisan anion assisted [3,3] oxy-cope rearrangement, The OH group is deprotonated by strong base, KH to furnish an oxy anion, which assists the oxy cope rearrangement. Deyo ds pe Qe The stereo relation between two hydrogens is cis. It can be justified by following stereochemical oftransition state ‘The two hydrogens are syn to each other cyclic transition state Problem 12.6 (GATE 2010) ‘The major product formed in the following reactions is: & = i 3 8 3 gz zg a g & & z Z g é g Updates & online help through forums are only available to those who purchased this book from the author at hit48 OH SDA 7 ii) H,SO, oH Answer: A Explanation * 3,4-dimethylhexa-1,5-diene-3,4-diol undergoes oxy-cope rearrangement to give octane~ which cyclizes by intra molecular aldol condensation in presence of acid. :/Iwww.adichemistry.conv H OH OH 9° fo OH cS sl H,So, S| HO pe bp OH OH {OH ~ Q ° H @ 2 2 i. Q ro) fy woyy Kjuo ajquyreae st yoog sitp yo Adoo yourBi10 oy, 0. H [3.3} sigmatropic intra molecular aldol reaction Problem 12.7 (CSIR JUNE 2012) ‘The major product formed when (3R,4S)-3,4-dimethylhexa-1,5-diene is heated at 240°C is: 1) QZ,6Z)-octa-2,6-diene 2) (2E,6E)-octa-2,6-diene 3) (2E,62)-octa-2,6-diene 4) (3Z,5E)-octa-3,5-diene Answer: 3 Explanation: * Itundergoes [3,3] sigmatropic Cope rearrangement upon heating to give cis-trans octa-2,6-diene 5 predominantly. This product is formed via a chair lke transition state. ‘The Cope rearrangement is also possible through boat like transition state leading to a trans-transproduet However its formed as minor product since the boat conformation is least favored. se A Hp eS 7 = = a WY a H & g 2 3 3 gz zg a g & & E Z g é g i redraw chai like (2Z,6E)-octa-2,6-diene a —> Major product H (3R,4S)-3,4-dimethylhexa-t,5-diene H 7-4 Liwtytee 9, Nay F > 4 boat like _(2E,6E)-octa-2,6-diene Problem 12.8 (GATE 2012) Identifiy the product formed in the following reaction. Updates & online help through forums are only available to those who purchased this book from the author at hit49 41) CH,=CHMgBr, THF 2)H,0 3) excess CH,C(OCH,),, PTSA, A A) 8) ° ome ©? ‘OC(Me)(OMe), a \ \ a“ ° OC(Me)(OMe) OMe Answer: B Explanation: * The Grignard reagent attacks from the less hindered face of the carbonyl group to givean allylaleohol, which is treated with Trimethyl orthoacetate in presence of acid, PTSA, to get a ketene acetal that undergoes facile (3,3]-sigmatropic rearrangement to furnish ay,5-unsaturated ester. The last step is also known as Johnson orthoester Claisen rearrangement. * The geometry at the double bond (Z) in the final product can be explained by more favorable chairl transition state. ~ Loaf ‘OH A a oaiid CH, ‘OMe 4" OMe ° <—. ° SH \\ Lome. OMe: Ne Johnson orthoester Claisen rearrangement IP JOU Og “UO ALysHUDYDIPE:ALALAY/sd}yy WHOA, A[UO aIgeHFEAR St YOO stIp Jo Adoo peurLI0 oy ‘yoyine Jo uossstutiad mnoypar yoo styp a1N4} ipdates & online help through forums are only available to those who purchased this book from the author at http://www.adichemistry.com/ oH a { Me 4 OMe pl. a 10. [So*Me ‘OMe H3C~ |SOMe Ke" EE A wg5om H Problem 12.9 5 Identify the product formed in the following thermal reaction,50 4 74 Hy "Ss 3) — 9 ahs Answer: 3 Explanation: * This conversion takes place through two sequencial [3,3] cope rearrangements. Big thine DES «LS dnywoy 1 ayqeqreae st 4009 stip yo Adoo jourdt10 ax, ‘The major product formed when (Z)-(2-methoxyvinylbenzene reacts with dichloroacetyl chloride in presence of triethyl amine is: 2 Problem 12.10 (GATE 2013) g The pericyclic reaction given below is an example of: S HO. e 2. a z to ayy : ] 8 Ho 3 A) [1,3]-sigmatropie shift B) [1,5]-sigmatropie shift 9 ©) [3.5|-sigmatropie shift D) [3,3]-sigmatropic shift 3 Answer: D & Explanatic a HO, 5 2 z fi — aoe BG z HO mi g F Problem 13.1 (CSIR Model paper) 2 a & CL OMe CL OMe Cl Ph CL Ph acl 2) cl 3) cl 4) cl Oo Ph Oo Ph oO ‘ome oO” “OMe Answer: 4 Explanation: Updates & online help through forums are only available to those who purchased this book from the author at http://www.adichemistry.com/51 ° OMe. CHK cL OMe C or Ph Net, o” Ph * Dichloroacetyl chloride furnishes a ketene in presence of base, NEt, * Thus formed ketene undergoes [22] cycloaddition under thermal conditions to givea cyclobutanone. :NEt, :/Iwww.adichemistry.comv hy wiogy Stu 91qujeae st yo0g stIp Jo Adod feursi0 a4, * Note that in contrast with the photochemical [2+2] cycloaddition reaction between two alkenes, the [2+2] cycloaddition ofa ketene and an alkene is possible under thermal conditions, even though orbital symmetry considerations predict that the thermal [2+2] cycloaddition reaction is disallowed. Itis due to the presence of two orthogonal -bonds in the LUMO of the ketene that allow the approach ‘= of the HOMO of the alkene at an angle to the ketene, * Stereospecificity: Cycloaddition of ketene with an alkene occurs stereospecifially, such that the geometry of the alkene is maintained in the eyclobutanone product. Hence the OMe and Ph groups maintain their spatial relation, * Regioselectivity: The electron deficient central carbon atom of the ketene forms bond with more 5 electron-rich end of the alkene. Note: Itis possible to remove the two chlorine atoms from the product just by heating with Zn in acetic acid. Problem 13.2, (GATE 2002) ‘The major product formed in the reaction of cyclopentadiene with a mixture of dichloroacetyl chloride and triethylamine a cl cl 9 aye y B) Cr » ° aye b) ove ° QO ° a Answer: A = i a 8 3 2 Fy a Explanati * The regioselectivity of the [242] addition of ketene and the diene is decided by favorable interactions between atoms with larger orbital coefficients, ‘joqne Jo uoIsssiuiod noyAL yoog sip SaNgEN cl Che A er TY I { | — I ° O° Updates & online help through forums are only available to those who purchased this book from the author at hit52 HOMO (shown partly) Problem 13.3 (GATE 2010) ‘The major product in the following reaction is: in 4) “Oo aD oe D) co Answer: B :/Iwww.adichemistry.com’ Z E 3 & g & = E & z B z Explanation: * It is Alder-ene reaction, vem eg) 4 iS l H H H * The stereochemistry of this reaction is shown below. The allyl and vinyl groups, on the eyelopentane ring formed, adopt trans configuration during the transition state. Transition state Problem 14.1 (CSIR Old Model Paper) ‘The major product formed in the following reaction sequence is: ‘JoUNe Jo uoJSsstULIad joy 400g stIP AINgLSIp OU OC_“;UIOD-CnSKHIOYDIPE-ALAL Updates & online help through forums are only available to those who purchased this book from the author at it53 Zz g 3 Cl NH,NH, E —_— z KOH 2 COOH g NH-NH g : 5 3B Answer: 2 E § Explanat 2 3 _* The hydrazone formed in the initial step undergoes elimination as shown below to givea conjugated = : alkene as final product. It isa special case of Wolff: Kishner reaction. e & = i 3 : 4 g ° ni nh nA \ = Com ce cos oc : rr CO This step is rather a simple H,0 rucleophile adaton followed orrction of by removal of water molecule pean tan water Problem 14.2 (CSIR Model Paper) ‘The compound formed in the following reaction sequence is: | 1) H,O,, NaOH (02) NH,NH,, KOH, 4 ‘CHO as a ‘Joye Jo UoISssUad Moy Yoo stIp aINgUNSIP YoU Og “/AtOD-CnsTUDYDAPE-ALAL Updates & online help through forums are only available to those who purchased this book from the author at hitUpdates & online help through forums are only available to those who purchased this book from the author at http://www.adichemistry.com/ 54 H,0,, ‘ool NH,NH,, | NaOH ~No KOH, 4 o OM Explanation OH OH + The last step is also known as Wharton reaction, which involves conversion of a,f-epoxyketones into allylic aleohols by using hydrazine. Problem 14.3 (CSIR Dec 2011) The correct sequence of reagents to be employed in following transformation is: CS ) i) mCPBA ii) TSNHNH, iii) ACOH iv) H,, Pd-BaSO, b) i) H,O,, NaOH ii) NHNH, ii) ACOH iv) H,, PaIC c)i) mCPBA ii) TSNHNH, iit) NaOH iv) H,, Pd/C d) i) H,0,, NaOH ii) TSNHNH, iii) ACOH iv) H,, Lindlar’s catalyst Answer: d . hindered side (from the bottom) preferred | sient azaenolate Me Problem 14.5 (GATE 2010) ‘The major product formed in the following reaction NNHTS_NaOMe, Glycol & : 4 Z 3 3 zg a g & 2 z 2 & 8 ye0° Sd O° ‘Answer: C Explanatior * Itisa Bamford-Stevens reaction. * Initially, the reaction of tosy| hydrazone with a strong base leads to a diazo compound. Inprotie solvents, the diazo compound abstracts proton fom the solvent and thus by forming a diazonium. Updates & online help through forums are only available to those who purchased this book from the author at http:58 ion, which subsequently loses dinitrogen to give a carbenium ion, Finally, thermodynamically stable more substituted alkene is formed fom the carbenium ion through bss ofa proton. HS Ss rans te al. Zthya Name aN) oN La aman ay AL, —— diazo compound ccarbenium ion Problem 14.6 (GUJARAT SET JAN 2004) ‘The major product formed in the following reaction is: 4) CH,Li A) oy 8) ow ° ey D) cr Answer: A :/Iwww.adichemistry.com’ Z E 3 & e g & = E & z B z Explanation: * Itis.a Shapiro reaction. * Two equivalents of methylithium, a strong base, abstract first the proton from the hydrazone and then the kinetically more accessible but less acidic a-proton to the hydrazone carbon to furnisha carbanion. * The tosyl group is eliminated from the carbanion to forma diazonium anion whi expulsion of N, to provide a vinyllithium compound, an organometallic. * The vinyliithium compound is treated with water to give less substituted alkene. e i g CHL CHL De Ts) —— [ue tg ut ts de Problem 14.7 (GATE 2011) ‘The major product formed in the following reaction ‘JoUNe Jo uo|SssTULIad joy 400g stIP AINgLSIp OU OC] “;UIOD-CNsKHIOYoIPE-ALAL Updates & online help through forums are only available to those who purchased this book from the author at hit59 i) 2 eq, of n-BuLi -78°C to0°C. ii) DMF 9 CHO ° A) oy 8) ~ S20 ©) “CHO Dy CHO Answer: C Explanation * In this reaction the vinyl lithium compound formed in the Shapiro process is treated with DMF to introduce a formyl group at the site of previously tosyl hydrazone carbon, adic con Z E 3 & g & = E g & z B z ui ur , Ts Bul Ne Ts_nBull nofts °C Nye SE ea ho 78°C were “ST 6) Z Dnee) , Ne ARES Ailes Senne, SN Lue H Wo Problem 14.8 (CSIR JUNE 2012) The correct reagent combination / reaction sequence for effecting the following conversion is: 1) a) Me,SiCH,OMe, n-BuLi; b) H,O°; c) NaBH,, MeOH 2) a) Ph,P*CH,OMe CI, n-BuLi; b) HO"; ec) NaBH, MeOH 3) a) NH,NHTS; b) NaOEt; c) CICOOEt 4) a) NH, NHTs; b) 2 equiv. n-BuLi; c) HCHO x ‘JoUNe jo UoJSssTULIad joy 400g StI AINgLSIp OU OC_“;UIOD-CNSHHIOYDIPE-ALAL Answer: 4 Explanation: * Itis a Shapiro reaction followed by introduction ofa hydroxymethyl group using formaldehyde. Itis similar to the reaction explained in the previous problem. Ts Ts H noNH ne uw + ut WN) dum Beg nBali oe oc Ne or Tec “Ts, -N, Updates & online help through forums are only available to those who purchased this book from the author at hit60 Problem 15.1 (CSIR Dec 2011) Identify X & Y in the following reactions. 1)PCC_ 2) NaOH (aq) ——> —— x (IR: 1680.om") ‘OH Pcc yi: 1720 om) NaOAc :/Iwww.adichemistry.comv Z E 3 & e 7 g & = E g & z B z a) X= ce) X= Answer: a 4 ao x 2 ‘0 J Explanation: * Initial oxidation of aleoholic group gives Citronellal with aldehyde group which undergoes acid catalyzed cyclization to yield Isopulegol. The pyridinium dichlorochromate sufficiently acidic to catalyze thecyclization. Isopulegol is further oxidized to isopulegone by PCC. * Isopulegone undergoes base catalyzed rearrangement to Pulegone. The IR peak at 1680 ent indicates the presence of conjugated carbonyl group. Hence X = Pulegone ‘OH pce an Pcc NaOH 1 7 pe - ‘OH °. ‘0 ‘CH, ye H Citronetlol Citronelial Isopulegol Isopulegone _Pulegone z i g 3 9 3 a g & 2 g a & 4 * However, oxidation with PCC in buffered conditions slows down the cyclization. Hence in presence of NaOAc, acting as. buffer, the reaction is confined to only the oxidation of alcoholic group to furnish citronellal. This is supported by IR peak at 1720 cm', which indicates carbonyl group without conjugation, Hence Y =Citronellal Updates & online help through forums are only available to those who purchased this book from the author at hit61 mags Citronellal Problem 15.2 (CSIR June 2011) CHO 4) CH,(COOMe), NaOMe J 2a :/Iwww.adichemistry.conv hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, Citronellal Explanatio * Initially the active methylene compound, dimethyl malonate undergoes Knoevenagal condensation with aldehyde group of Citronellal, which undergoes Alder-ene reaction to give the final product. The entire process is known as Knoevenagal-ene reaction, Note: Here decarboxylation does not oceur since the Knoevenagal product is not treated with acid, The temperature is increased without adding acid. Hence no decarboxylation. & = i 2 3 3 gz zg a g & & z Z g é g 7‘ _COOMe £00Me Meo” -H-HC ——> Sc + MeOH \a ‘coome ‘coome 1 Ss OH COOME 44.0 ~-000Me cooMe > COoMe J J I [ovo coome _ &e _ i -COOMe x boone maton co0Me Updates & online help through forums are only available to those who purchased this book from the author at it62 Stereochemistry of Alder-ene reaction conMe CO,Me Problem 15.2, ‘The major product formed in the following reaction S ° ahha, O, 3 oO, S Br "OH ‘O a a~ :/Iwww.adichemistry.com’ Z E 3 & g & = E & z B z Answer: B Explanation * Itisa carbonyl ene reaction ofcitronellal in presence of Zine bromide to give Isopulegol. ‘JoUNe Jo uo|SssTULIad joy 00g StI AINgLSIp OU OC_“;UIOD-CnSHHIOYDIPE-ALAL Updates & online help through forums are only available to those who purchased this book from the author at it carbonyl ene reaction ZN { Redraw oy ; 4 Problem 16.1 (CSIR June 2011) on A + pence eee cS OH (2S)-butane-1,2,4-triol OH OH ato HOY) 0 ~~~ O_O O_O 0 6 * * : Xe sown a) a):/Iwww.adichemistry.conv Updates & online help through forums are only available to those who purchased this book from the author at ht 63 Explanation a * Butane-1,2,4-triol forms an acetal with 3-pentanone to give a 1,3-dioxolane (a 5 membered ring) as & major product. The hydroxy groups onadjacent (| & 2) positions take part inthis reaction. E Formation of 1,3-dioxane (a six membered ring) isomer as in options a & b is less preferred due to steric factors. 3 * p-TSA, p-toluenesulfonie acid serves as acid catalyst. z Eg oH g oH ‘OH e oon / g 201) ‘OH ( ‘OH 5 AS H p-Tsa ° 5 cc — & oF. ~~ > g H OH x} > GH g [se 2 oH Note: Work out the stereochemistry at chiral carbon. In the option , the configuration at 2nd carbon is. retained and incidentally it has S configuration as in the trio & = i 2 3 3 gz zg a g & & z Z g é g Problem 16.2, (IISC 2009) The product of the following reaction is: eons [Mey-00:0Me)_F,0C00H BON CHye -78°C NHMe Oo Me, .CO,CMe3 Oo A) Ow » CF Oe » (J Dea Answer: D Explanation: * In presence of Trifluoroacetic acid, the Trimethylsilyloxy, OTMS protecting group on furan and the64 tert-Butyloxycarbonyl, BOC group on nitrogen are removed, Then the OEt group is replaced by furanol. 0. _oTMS Cr* uw _FseCO0H | 2101 er NHMe Ts 806 Ba Mex, -CO,CMe, ~ z “7 g 3 ne eo a He? 3 © Problem 17.1 (CSIR Dec 2011) g ‘The major products M and N in the following reaction sequence are: hy wiogy Stu 91qujeae st 00g stIp Jo Kdod feursi0 a4, Li/lig.NH, mCPBA (1eq) —— 9 {BuO ‘OCH, a)Ae O Be ‘or 2) AS O B ‘OCH, ‘OCH, + OCH, ‘OCH, ° 3) A= 4) A= = ‘OCH; ‘OCH; ‘OCHs ‘OCH; Answer: 2 Explanation: * The first step is Birch reduction. It gives a 1,4-hexadiene with more substituted double bonds. nNH, solvated electron: - oct, Aon H ‘OCH; stable radical anion z i 2 3 3 9 z a 2 g 2 Z z 4 & . g * The regioselectivity of this reaction can be explained by taking into consideration of stability of radical anion, The radical anions formed by addition of electron to ipso or para to methyl or methoxy groupsare 5 less stable due to electron donating nature of these substituents. “S, “tt H H (Other possible radical anions but unstable as the electron donating groups, Me & OMe increase the electron density at ipso and para positions and thus by decreasing the stability. Updates & online help through forums are only available to those who purchased this book from the author at hit65 * The next step is epoxidation at electron rich double bond. Since double bond attached to methoxy group is more electron rich due to +M effect, the epoxidation occurs selectively at this double bond & z 2 ‘ocH 3 ( a ‘OCH, = g ‘SOCH 5 B %, 4 a 2 ° = 2 = 8 = : ‘ol ‘al ‘ol . & Transition state = : 3 Problem 17.2 (GATE 1997) = How do you carry out following transformation? . oe Oh, Answer: * Birch reduction followed by mild acid treatment gives a B,y-unsaturated ketone, which is isomerized to an o.,B-unsaturated ketone upon treatment with strong acid, OCH, ° oO Li/ liq, ‘6H “an é conc HS, Cy CcH4) fsomerization \" cy, Note: Direct addition of cone. ng to the inital product also serves the purpose Probable mechanism for isomerization: oye Jo uoIsssiUad Moy Yoog stIp aINgUNSIp ou og “ttOD'nstUDYDAPE ALAC H 5 os! ° S=-a=—OL ‘CH. 4 CHy ‘CH 2 Problem 17.3 (IISC INT PHD 2008) ‘The major product in the following reaction will be: COOH 41) Na, lig.NH,, THF (2) Mel cooMe Me cooMe Updates & online help through forums are only available to those who purchased this book from the author at ht COOMe COOMe °O et oer Answer: B66 Explanation * Birch reduction of benzoic acid gives 1,4-dihydrobenzoic acid. The -COOH group is electron withdrawing and also a strongly activating group. It facilitates reduction at para and ipso positions. The reduction is also possible even without the presence of aleohol due to strong activation by -COOH group. * In the present case, the intermediate dianion formed after reduction at para position is stable and can bbe methylated at ipso position using Mel. Z E 3 & e g & = E g & z B z = 8 s NH Ba UL na + eINHsl, # solvated electron q COO'Na® coo Na” Me COOMe -O os (I Oo eINH, a _2Mel, G = Nne"Ie 7 dianion: de ae Note: Under Birch conditions, the -COO: group cannot be reduced since it is electron rich. Problem 17.4 (JAM 2011) Write the structures of the products A to D in the following reaction sequence, = N’ OSi(CH,)3 no re pte eZ ono, 4 Explanation: * Inthe first step, Birch reduction of N,N,4-trimethylaniline results in immediate isomerization ofthe initially formed kinetic product: 1,4-cyclohexadienamine to a conjugated 1,3-cyclohexadienamine, even without using any acid. * Then the enamine is hydrolysed to a .y-unsaturated ketone, which further undergoes isomerization to a soa ketone under acidic conditions. Aye ° ° tat HO" isomerization Bun — K 8 * Finally, the conjugated enone is made to react with 2-trimethylsilyloxy-1,3-pentadiene, a silyl enol ether ina Diels-Alder reaction to give an adduct, that is hydrolyzed to remove trimethylsilyloxy group. ‘JOUINE Jo uoIsssiUad oy Yoo stIp aINgUNSIP YoU Og “/AKOD-CnsTUDYDAPE-ALAL more more ae end oe end ree __a 40,810 Ho" © ‘Diels-Alder ° ° c D Updates & online help through forums are only available to those who purchased this book from the author at ht67 The Diels-Alder reaction between silyl enol ethers and conjugated enones is very rapid since the energy = of HOMO of diene is increased due to hetero atom substitution, This results in results ina reduction in the & energy difference between the HOMO of the diene and the LUMO of the dienophile The regeoselectivity of Diels-Alder reaction can be explained using Density Functional Theory, DFT. According to DFT concept, the atoms with highest local nucleophilcty index, interact effectively with atoms with highest local electrophilicity index, The electron releasing groups, ERG at one end on a diene makes the other end (unsubstituted) of the diene more nucleophilic, Whereas, the electron releasing groups, EWG on one end ofa dienophile makes other end of double bond, more electrophil Hence these unsubstituted parts will react with each other more rapidly heading towards observed regioselectivty. Problem 17.5 The likely major product formed in the following reaction sequence ‘ory KN Zw He A ot “-BUOH/ THE MeOH » ° 2 9 3 AO 4) ° © Eo tho “oro co ‘0 ‘Oo ‘Oo 2 :/Iwww.adichemistry.conv z 3 3 E g & 5 EB z g & ¢ 3 z Answer: 2 Explanation; * Under Birch reduction conditions, initially, the carbon at para position of amide group of N-pyrrolidinyl 2-methoxy-5-methylbenzamide is reduced and subsequently a dianion is formed which can be trapped by 2 allyl bromide. Thus both birch reduction and allylation are achieved. * Acid hydrolysis furnishes a ketone that undergoes subsequent Cope rearrangement upon heating ina suitable solvent. “oro kN on “PBUH / THE ‘ome ss Oo __ ho - 7 La 'D MeOH ° Problem 17.6 Identify A & B in the following reaction sequence. ‘JoUINe Jo uoISssiUad Moy Yoo StI} aINgUNSIp ou Og “/Atoo:CnsTUUDKAPE-ALALY Updates & online help through forums are only available to those who purchased this book from the author at hit68 OMe Li tig. NH, 1)0,/Me,S —__> a—___+8 tBUOH 2) NaBH, Ho. OMe OMe Me CHO So ‘OH Explanation: * Ozonolysis cleaves the double bond at OMe group since this double bond is more nucleophilic than that containing methyl group. It is well known that methoxy group can donate electrons through +M effect. * Finally, NaBH, can reduce only the keto group since it cannot reduce ester functional group. Sor Lis tig. NH OMe.0, coome NaBH, Com ‘-BuOH Me,S a ‘OH oy Answer: 1 :/Iwww.adichemistry.comv hy wioyy yuo 91qujeae st yo0g styp Jo Adoo feursi0 a4, Problem 18.1 (CSIR Dee 2011) ‘The major products M and N in the following reaction sequence are: ‘JoUINe JO UOISssHULIad Moy Yoo StI aINgUNSIP YoU Og “/AKOD-CnsTURDYDAPE-ALALY 1) PhP, H,O 1) Hg(OAc), ——> um ——+n ANS 2) Cbz-Cl, Et.N 2) NaBH, a) b) M ooo A =< ecoen neon H coosn oa Secon eGo ‘CooBn ‘Answer: d Explanation: * The first step is conversion of azide (N,) group to amine (NH,) group using PPh,, This is known as Staudinger reaction. Updates & online help through forums are only available to those who purchased this book from the author at ht* Thus formed amine is N-protected by carboxybenzyl (Cbz.or Z) group employing benzylchloroformate, PhCH,OCOCIin presence of a base, :/iwww.adichemistry.conv CeO AN Z E 3 & e g & = E & z B z Benzyl 10k from the author at htt * Trans-aminometallation of olefin using mercury(I) acetate leads to cyclization to furnish a 2,5- 2. & disubstituted pyrrolidine rng. Initially, the r-system is activated by metal and followed by nucleophilic? attack by nitrogen. As usual, final demercuration step is done by reduction with NaBH,. Note that the Cbz group is intact in this step. 0 Ne , eo x COoBn H Problem 19.1 (CSIR Dee 2011) ‘The reaction given below proceeds through: ‘Joy Ne Jo UOISSsIULIOd oy Yoo stp aINqUASIp ou Og] “LOD: Updates & online help through forums are only avilable to those who purchased tis70 : LK ' NaHco, Zz 3 z CooH ‘Oo g \ a e g ee) eh ») o 4) z 8 z 3 COONa | COONa COONa 1 COONa g B answer: a = © Explanation: E S * This reactionis called lodolactonization. = g *It.goes through the formation of positively charged iodoniumion followed by intramolecular ring dosure 3 2 toafforda lactone. 3 5 F \ NaHiCo, 2 a — — CooH oo (oo i & ° * According to Baldwin rules, which describe the kineti feasibility ofring closure, S-exo-tet ringclosure is favored over 6-endo-tet ring closure. 41 : M — S-exo-tet a . 0 _0”So to) —! f G-endo-tet 0. ‘Oo 0 Terminology: + ‘exo’ indicates the bond broken during ring forma inside the ring * fet’ means the carbon undergoing ring closure is tetrahedral is out side the ring and ‘endo’ means that is Problem 19.2 (CSIR Model Paper) z i g 3 9 3 a g & 2 g a & 4 COOH IKI Zw SnBug ———> x —__» y NaHCO, AIBN Updates & online help through forums are only available to those who purchased this book from the author at htUpdates & online help through forums are only available to those who purchased this book from the author at http://www.adichemistry.com/ n Explanation: * Initially, iodine attacks the double bond from opposite side of carboxyl group, which givesan iodolactone with trans configuration, COOH LK cy NaHCO, * Inthe next step, iodine is substituted by allyl group in a radical mechanism using tributylallyltannane, This reaction is initiated by AIBN, a free radical initiator. This reaction is called Keck allylation {het eo f.+ nen cN CN. CN AIBN (2,2'-az0 bisisobutyronitrile) FO Ai eo SO + stg cN cN Chain propagation fo) HY. wen MI a Oe , eo O Buss ROWS “~~ \ IP JOU Og “UO ArysHUOYSIPE:MLALAYy/dhyy WHOA, ATO aIgeHFEAL St YOO stIp Jo Adoo pourLI0 oy ‘yoyine Jo uossstutiad mnoypar yoo styp a1N4}2 Problem 19.3 (CSIR June 2011) COOH 1) N-Bromosuccinimide 2) KO-tBu 0, 0. » tus 5 (mal 5) Cop 4) Core 4 hy wioyy Su 91qujeae st yo0g stIp Jo Kdoo feursi0 a4, z — answer: 3 E explanation: 5 _* NBS supplies bromine in low concentration whieh attacks the double bond by giving a bromonium ion. 3 This is followed by nucleophilic attack of oxygen from the backside to give a lactone. g oO z 9° Br, atm fr 0 0 6 * Dehydrohalogenation in presence of strong base, t-BuOK gives double bond as shown below. Notice the antiperiplanar arrangement of Brand H groups on adjacent carbons during elimination step. The hydrogen on the other carbon in the lactone ring cannot be eliminated since it cannot satisfy antiperiplanar requirement forthe elimination. Henee the product given in the option 4 is formed. 9 Br, & = i 2 3 3 2 zg a g & & z Z g é g Problem 20.1 (CSIR Dee 2011) HCO. 4) NHC, NaCN 4) UAH, Bn0. ——_ x + y 2) H,0° 2) CH,COOH Updates & online help through forums are only available to those who purchased this book from the author at hitB tie, ite, HOOG: HNO . a)X=—Bn0. b) X= Bno. ° ° a axe tie, NHAc Hp NHAc ACO. ACO, HOOC: 5 Ho “B. Si, xe xe ©) X= Bro. a) y ‘Answer: a ~- Explanation: :/Iwww.adichemistry.com’ Z E 3 & e g & = E & z B z = * Thealdehyde group is subjected to Strecker amino acid synthesis reaction by treating it with NH,Cl S &NaCN followed by acid hydrolysis. 2 3 NH,Cl+NaCN ——» NH + HCN + NaCl g 2 BR 5 E & INC. NH2 Hooc_ NH g % HAO. 10° Co. & 2 Bno. eee 3 Bno. 3 Q 8 i ° 3 5 2 g reduced to -CH,OH group conveniently by using LiAIH, 2 a a g NH, e 2 Hooc. HOH,C. NH z 3 woo HA Co, z g — é g sno_/\, eno\_/\, & ie ° ° & 2 z q 2 _ * Thus formed amino alcohol is condensed with acetic acid to give a4,5-dihydro-1,3-oxazole derivative. & S z z z £ kom, "OY 5 g ‘0 a > 3 ‘. A HO. Z : Hore HO NH wory a € HOO. Ho. ©. s 5 3 2 BnO. Bn0.\_/\, —> Bro ne 2 3 °. ° S z “- o 5 2 2 5 7 & 2101 Problem 31.1 In the following reactions, the major products, X & Y, respectively, are: HNO, mCPBA ——— + x » & ‘COOH B) & ‘COOH COOH °- ‘COOH % ° D) & ‘COOH O-\y ‘COOH :/Iwww.adichemistry.comv hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, Answer: B Explanatio _mcpea AX i oO Nalco, So 65% 35% * Baeyer Villiger oxidation of camphor with mCPBA in buffer conditions, gives the major product (65%) that is formed due to migration of a tertiary bridgehead carbon rather than a methylene group. The Criegee intermediate can be formed either by exo or endo attack of peroxy acid. Ifit attacks inexo fashion, the migration of bridge head carbon is more favored since it goes through chair shaped trarsition state. Bridge head carbon migration with more favorable char shaped TS Exo attack — pak — Ay A Qa ~ +r 0-0) & : 4 Z 3 3 zg a g & 2 z 2 & 8 oe App he- K oO ok, ° S H Migration of methylene carbon with less favorable boat shaped TS Updates & online help through forums are only available to those who purchased this book from the author at ht102 * However, in acidie conditions, the major produet formed is due to migration of methylene group. In 3 this case, the Criegee intermediate is formed due to endo attack and the migration of methylene group is 8 ‘more favored since it goes through chair like transition state, Migration of methylene carbon with more favorable chair shaped TS wn i Bue ndo atlack = —- o= Ay ar ° 4 — 6 c= 0 O° Sol ° Bridge head carbon migration with less. favorable boat shaped TS :/Iwww.adichemistry.comv z 3 3 E g & 5 EB E g g ¢ 3 z Problem 31.2 (USC INT PHD 2008) ‘The major product in the following reaction will be: CF,CO,H ————- x CHCl, ° A) B) 2 ‘OH Ho. OH 07 Ph 07 Ph 07 ~oPh of rh Answer: D Explanation: * Itis Baeyer villiger oxidation involoving migration of 3° bridge head carbon since it has more migratory aptitude over phenyl ring, -0F 00, roe Be 00; I, oF ° 2, of pn ‘JoUNe Jo uo|SSsTULIad joy 400g StI AINgLSIp OU OC_“;UIOD-CnSHHIOYDIPE-ALAL Problem 31.3 (JAM 2011) Write the structures of A to C in the following reaction sequence. Updates & online help through forums are only available to those who purchased this book from the author at ht103 41) CF,CO,H, CHCl, CH.CHCH, ——_cH,Coc! 2) NaOH, A. ——_> a> 8 —— . HCI, AICI, Ach, 3) 0" Explanation: * The first reaction is Friedel-Crafts alkylation, The attacking species is isopropyl carbocation, a more stable secondary carbocation. * Next reaction is Friedel-Crafts acylation at less crowded para position to give a ketone, B. * The ketone, B is subjected Baeyer viliger oxidation with peroxytrifluoroacetic acid. The aryl group is rearranged on to oxygen since it has more migratory aptitude to furnish an ester. Remember that methyl group has least migratory aptitude. * Finally, para isopropyiphenol, C is formed upon hydrolysis of ester with a base followed by protic workup. :/Iwww.adichemistry.con’ fy wiogy Su 9}qujeAk st 00g stIp Jo dod eUTsI0 a4, c CH,CHCH, ee CH,COCI CF.COH i) NaOH, A HCI, AICI, “cH, Cl, ii) HO" °. OH Problem: 32.1 The correet description of the following two reactions is that: yak Abe a : ee —— PhCHO + P- ae Oo A) both P & Q undergo or cleavage reaction, B) P undergoes only Norrish type IL reaction, whereas Q undergoes only Norrish type I reaction. C) Qgives P by photochemical chair to chair interconversion of the cyclohexane ring. D) both P and Q undergo Norrish type I reaction, but Q gives benzaldehyde through this mechanism. Explanation: * Norrish type II reaction is possible only with P since the abstraction of -hydrogen is possible through 6 membered cyclic transition state. The axial y-hydrogen can readily participate in case of P. SL SIL ABS * However, abstraction of y-hydrogen is not possible in case of Q. z i g 3 9 3 a g & 2 g a & 4 Updates & online help through forums are only available to those who purchased this book from the author at ht104 Neither of these two y hydrogens can be abstracted. No cyclic transition state is possible. . In case of Q, only Norrish type lis possible as shown below. Cleavage of bond between carbonyl carbon and « carbon Lay we - Q oO ‘Abstraction of B hydrogen to give an aldehyde and a hydrocarbon YE or od + ProHo ™~ oO 4 :/Iwww.adichemistry.comv hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, * It isalso possible that the initially formed free radicals can join again, Recombination of free radicals SOs, LekoOe > ae Problem 32.2 (CSIR JUNE 2012) Structure of the starting material A in the following photochemical Norrish reaction, & : 4 Z 3 3 zg a g & 2 z 2 & 8 * It isa Nortishel type reaction leading to formation ofan acyl and more stable allyl radical due to homolytic cleavage of bond adjacent to carbonyl carbon. This is followed by formation ofa cyclopropane ring formation and subsequent ring closure. y ot ait it-es Updates & online help through forums are only available to those who purchased this book from the author at ht105 Problem 32.3 a What isB inthe following reaction sequence? a ‘Ot 2 ost Ey 3 z z cine aie 5 8 ——> a———_+B8 g 2 Ph a & 4 g 2° Ph 3 g 9 Ph aA 3) ou 4 cu E g oH ST Fon CooE! CU coor, & £ g Ph OH 3 Answer: 3 g F Explanation: * The first step involves Norrish type II reaction leading to formation of eyclobutenol ring which is opened in photochemical conditions to give a diene system, A that subsequently undergoes Diels-Alder reaction to give final product, B. Ph Ph Ph ° cooet KY ‘ort A Cox X een Phenyl> tertiary > secondary > methyl CH3 OH CH3 OH Hy OH H3C _o-J Hc 0 Hef eC} >) Forte HEX QH CoH (QH; CoH HsCa\ H HsCp C2Hs — HsCp Cas Ga * Onthe other hand, in the second route leading to B, intially, tosylation of less hindered secondary alcoholic group occurs preferentially over sterically crowded tertiary one. The tosy group is removed underslighly basic conkitions to furnish ess stable secondary carbocation, It = undergoes rearrangement of ethyl group on the adjacent carbon, Remember that the migratory aptitude of JOAL YOO sip amNqUISIP ou OG, ethyl group is greater than that of methyl group. 2 The overall conversion is called semi pinacole rearrangement. 2 3 CoHs e CoH 5 Problem 33.3 ‘The major product formed in the following reaction sequence is: Updates & online help through forums are only available to those who purcha:107 i) O80, pyridine (e} a il) p-TsCI, pyridine ill) LiCIO,, Caco, oO Answer: 3 Explanation * Osmium tetroxide forms diols from alkenes. In this case, only the sterically less-hindered exo double bond reacts to furnish a diol Inthe second step, Tosyl chloride (p-toluenesulfonyt chloride) reacts with alcohols to forma sulfonate ester derivative, It will react with the sterically least-hindered alcohol group. Finally, the tosylate is subjected to mild basic conditions in presence of LiClO,, which presumably acting asa Lewisacid to facilitate ionization of the tosylate to follow a semi pinacole rearrangement of vinyl group ofthe ring. m OO ce Sf SX 030, PTs ts, A pyridine nae “caco, Ho OH Problem 33.4 (JAM BT 2009) ‘Treating the following diol with strong acid gives a product which displays a prominent absorption band at 1710 em in its IR spectrum. The mostly likely structure of the produc QL PR A) B) c) D) GeO St ut Ye Answer: D :/Iwww.adichemistry.conv hy wioyy Kjuo ajquyreae st yoog sitp yo Adoo joursi10 a4, & = OE 2 8 3 gz zg a g & & z Z g é g Explanation: * Strong IR absorption at 1710 emt" indicates presence of a carbonyl group. Hence we can rule out options Band C. * Since diols undergo pinacole rearrangement to give a ketone, the correct option must be D. Updates & online help through forums are only available to those who purchased this book from the author at ht:/iwww.adichemistry.com’ Updates & online help through forums are only available to those who purchased this book from the author at hit 108 [uo ajqupeae st yoo styp yo doo peursiz0 a4, HE FE <4 F bs EOE een pay Oh" er PO Tethyt > group Note: Despite the fact that pheynyl group has greater migratory aptitude than methyl group, the strain in § the cyclobutane ring may discourage this migration, Hence the major product is formed due to migration of methyl group. 3 F Problem 34.1 4 OTs cb OH ots CO CSOD . 5 ° OH Answer: 2 Explanation: 4 H 4 OTs KH (51s a co HO ° ° q * The bonds shown in bold are antiperiplanar to each other and hence elimination is possible by producing trans geometry at the formed double bond. Problem 35.1 In the reactions PhCHO acetone X <—— D-glucose ——> Y Ht H the major products X and Y, respectively, are JoUINe Jo UOISssUad oy Yoo stIp aINgUNSIp YoU Og “/AtOD-CNsTUDXDAPE-ALALY109 Zz 8 1) pr Me ¢ PaYo OFS Q we ° a and o 8 1 on 3 L ‘OH 2 By “i : 8 Ph] 0. & SemPh and ws 2 z 4 HO no ‘OH 5 3 E g a °. Me. 0- e g Pho] oo 0-0 Me a 2 ‘0 mph and = Me” 0: = $ Me 3 Hd Hd 5 MeO 4) pro XO] 0-0 Me On. and MeO: YS HO’ on ‘OMe HO Answer: 4 Explanatior * The open chain form of D-glucose can exist in equilibrium with pyranose and furanose form. * Benzaldehyde forms acetal with pyranose form of D-glucose by reacting with the -OH groups at 4th and Sth carbons. ‘The new six membered ring is trans fused to the pyranose ring of glucose. The phenyl group takes equatorial position in the acetal. Pry Ho Hf prNo Hats Ho. HO ‘OH HO ‘OH * However, with acetone, the six membered cyelic acetal is not formed since one of the methyl groups ofacetone will be axial Me oH ce Mer 0 Not preferred due to axial interactions Fo. Ee ‘OH z i g 3 9 3 a g & 2 g a & 4 * And moreover * Hence acetone reacts with the furanose form of glucose to furnish a double acetal as shown below. Updates & online help through forums are only available to those who purchased this book from the author at hit110 Zz Me a )-Me Zz on? z OH 8 of O.-0 Me g HH Xi & z a & a 7 Hd zg Es HHO 9 & z ‘Me a g me 5 3 E “3 _* Thea-D-glucofurranose form has two pairs of cis diols at 1,2 and 5,6 positions, with which two g acetone molecules react by giving a double acetal. g Also note the stable cis fusion of two five membered rings in the final product. & : z SCHEMATIC REPRESENTATION OF CONVERSION OF OPEN CHAIN FORM OF D- e GLUCOSE INTO PYRANOSE AND FURANOSE FORMS. & : 4 Z 3 3 zg a g & 2 z 2 & 8 Updates & online help through forums are only available to those who purchased this book from the author at hta OH OH HO ‘CHO OH OH :/Iwww.adichemistry.com’ Z E 3 & g & = E & z B z Flip entire mpiecule by 90° Hon y Hoon H. HOH OHH H¢ IH = = oH OH HAO HO ‘0 a OHOHH OH ol HOH rotate the bond betwen 3rd & th carbons without changing the donfigurations at these cartons HO on rotate the bond betwgen 4th & 5th carbons, without changing the dofiguratons at these |) Ko a ‘JoUNe Jo uo|SssTULIad joy 00g StI AINgLSIp OU OC_“;UIOD-CnSHHIOYDIPE-ALAL Updates & online help through forums are only available to those who purchased this book from the author at ht112 Problem 35.2 (GATE 2010) Z In the reaction sequence, 8 GH,OH = Ly i, Hg(OAc),/MeOH (CH,),CO. g 4 —___——_—_ x Y 2 HO ‘oH // ji, NaBH, HCI S aa a z 2 the major products, X and Y, respectively, are: g 2A HO B) HO Ho | 3 ~~ ° ie z 8 O08 a oF 2 wt wLLP gH i z Med MeO Meo! Meo) 5 2 °) HO s D) HQ, HO 3 07 0 XS He pe 0 i Oo ‘ome oS ‘oMe ‘OMe ‘ome Explanation: * Inthe solvo-oxymercuration, the Hg attacks from the less hindered side and the OMe approaches from the top side and attacks the carbon-1, adjacent to ring oxygen, since the positive charge on this carbon is stabilized due to +M effect of ring oxygen. * Demercuration is achieved by sodium borohydride to furnish a deoxy sugar. * Inthe final step, protection of OH groups on 4th and 6th carbons is achieved by using acetone in presence of dry HCL However, a six membered cyclic acetal is formed instead of five membered one even though there is & = Reo. KO AcOH MeOH = 5 Ac z & OAc 3 4 & Be fo) g 2 EO one z 3 Keo & 8 = : Q & © 2 2 2)A= Ac & Be < : Roc ARO. OMe z Br oe e tr OAc ’ Zz 3) A= we & BA Roo Br oN : OMe OAc OAc ° © 4) A= Act & BA who “Reo “feo “Reo Answer: 2 Cy el Explanation: * The displacement of acetyl group on first carbon from either of or B anomeric forms of glucose pentaacetate furnishes a-acetobromoglucose (tetraacetyl-a-D-glucopyranosyl bromide) as major product under equilibration conditions. The a-isomer is is more stable due to anomeric effect. OAc nite Oo B-isomer -= BR » Minor product OAc Q isomer Major product Hi fajor produc —— MRO Br & : 4 Z 3 3 zg a g & 2 z 2 & 8 * The a-acetobromoglucose undergoes nucleophilic substitution reaction with methoxide to give I- O-methyl-2,3,4,6-tetra-O-acetyl-B-D-glucopyranoside as major product. This reaction involves spontaneous S,1 like loss of Br ion followed by intermolecular reaction with carbonyl oxygen of adjacent ester group to give an oxonium ion, which subsequently undegoes backside S, 2 displacement by methoxy group with the inversion of configuration. Updates & online help through forums are only available to those who purchased this book from the author at htOAc OAc Roo — Reo! x Problem: 36.1 ‘The major product formed in the following reaction O- os Pd(OAc),, PPh, :/Iwww.adichemistry.com’ Z E 3 & e g & = E g & z B z z = Answer: 3 2 = Explanat g 2 *Itisa Heck reaction, 3-phenyleyclohexene is formed as the only product instead ofexpected2- © phenyleyclohexene, due to requirement of syn elimination of hydride. e 4 i 3 2B 2 2 z 3 5 1 3 & Phy co 2 g Pa zg 2 fT PhP” oxidative addition e a ge 3 a 3 reductive elimination PPhs 2 2 z a 2 2 z c mo | ? i 5 3 a Z 5 g 4S 7 PPh 3 2 Ph——Pa*+—1 z z SYN PhP SYN B Behyaride +> addition 2 elimination aw Phy 2 Ph ba 3 g nee \ & 5:/Iwww.adichemistry.con’ Updates & online help through forums are only available to those who purchased this book from the author at hit 115 Problem 36.2 Choose the species that is not an intermediate in the following palladium catalyzed Heck reaction, Br 0. PAlPPh, - alt ae SO! ° EUN Br Br Pd(PPhs)2_ (PhaP)Pd 0 ° i 1) ye So) 4) Pa(PPhs)2 er aPPMsbe 0707 Answer: 2 " Br HBr ee _PPhs reductive elimination Pd 7 Pt oxidative addition Phy ° HPd er a rw poe. Pere PPh; “Y ye Br Pye ° o A x-complex Pho Mize PhsP— popes Br » SYN Be-hydride \ elimination "44 , 0" H AA HQ PhgP—Pd—PPhg SYN ~ fj addition br Ph PhsP—Pd=—PPh, Rotation of \ C-C bond to give br more stable conformation Z E 3 & e g & = E & z B z ‘JoUNe Jo uo|SssTULIad joy 00g StI AINgLSIp OU OC_“;UIOD-CnSHHIOYDIPE-ALAL116 Problem 37.1 (GATE 2004) ‘The major product formed on nitration of N, N-dimethylaniline with conc. H,SO, and cone. HNO. is: A) NMey —B)_-NMez ©) NMe, D) Me, Answer: A. No2 NO2 Explanati * The nitration of N.N-dimethylaniline using 85% H.SO, gives 45% meta-nitro product and 38% para- nitro product along with N,N,N’,N’-tetramethyl benzidine. * N,N-dimethyl aniline is protonated in strongly acidic medium by forming an N,N-dimethyl anilinium ion, PhNHMe,*. 5 Since NHMe,” group is deactivating towards electrophilic substitution due to -I effect, the nitration occurs mostly at meta position, :/Iwww.adichemistry.com’ zZ 2 ya - ya o nj wuoyy Aluo ayqepreae st y00g stip Jo Adoo poursi10 oy : Why para product is also formed? * Inthe reaction mixture, smallamount of free N,N-dimethylaniline is also present in equilibrium with its § anilinium salt, This free form is highly reactive and gives para product and favors the equilibriumto the left 2 side. oyine Jo uoIsssiuod moyAL Yoo stIp aINGUNSIp YOU Og “ALOD-AA Ve 4 * However, below 83% concentration of H,SO,, meta substitution is seldom observed and the composition of para product and N,N,N’,N’-tetramethyl benzidine increases with dilution of sulfuric acid. It is also interesting to note that, with dilution of H,SO,, the major product is NN.N’,N’-tetramethyl benzidine rather than the para isomer. For example, 63% of benzidine derivative is formed when 74.7% of H,SO, is used. This reaction occurs through ion radical-radical pair mechanism, * Ortho product is also possible but formed in less amount due to steric factor. Problem 37.2 (GATE 2004) In electrophilic aromatic substitution reactions, nitro group is meta-directing, because the nitro group: a) increases electron density at meta position. b) increases electron density at ortho and para positions. Updates & online help through forums are only available to those who purchased this book from the author at htUpdates & online help through forums are only available to those who purchased this book from the author at http://www.adichemistry.com/ 117 €) decreases electron density at meta position. 4) decreases electron density at ortho and para positions. Answer: d Explanation: * Nitro group is eleetron withdrawing group. It withdraws electrons both by inductive as well as, mesomeric effect ic, both-I & -M group. Among these, mesomeric effect has more effect on the reactivity In the resonance forms that can be written due to -M effect of nitro group, the positive charge is more distributed on ortho and para positions. Hence these positions become less reactive towards electrophilic substitution, when compared to meta position. QV. Oo 0 OY oO 0 “ Nye Nw r The positive charge is more concentrated on ortho and para positions making these site less reactive towards electrophilic substitution * The comparison of resonance forms of Wheland intermediates formed during attack of eleetrophile, E'isillustrated below. ‘The Wheland intermediates formed, during ortho and para attacks are less stable, since one of the contributing structure is east stable due to presence of positive charges on adjacent carbon atoms. -ausnayj:diny wioy {uo ajqupeae st yoog stip Jo Adoo feursi0 a4, a : i 2 8 3 2 g118 2 3 e 0" on 0 | oo E ortho attack | Sw iN” Aw 8 — H H Hg E e| es z e e 5 B Least stable g 3 > > g 0, OM Ores Sy re xr Sy 8 g O E* |metaattack | 'V Ne = > =<—~@ 2 Cy ee dy : E F Psy? Oe? & para attack He —G Ir ©) Least stable * The summary of above points are illustrated in the following free energy diagram. Not only the activation free energy required for meta attack is less, and also the Wheland intermediate formed is more stable, Transition stale i, ortho & para attack / meta attack : : 3 9 3 a 2 z z 3 g & 3 Free energy Wheland intermediate Reaction coordinate Updates & online help through forums are only available to those who purchased this book from the author at ht119 Zz 3 Problem 37.3, (JAM BT 2011) E Identify the major product of the following reaction. g 3 AIC! & z + —s & pOrA : £ 9 9° & 2 4 2) Oe 3 4 OH OH 2S answ & 8 g 3 2 Explanation = &. * AICI, generates stable secondary carbocation from the epoxide. The carbocation acts as g electrophile and attacks benzene ring. z Be OWN ONG | ovrCl, OA'cl, OH o-cd-ot=o* Problem 37.4 (GATE 2010) ‘The major product formed in the following reactions is: 9 Excess +L anhydrous o AICI, a) ° B) ° °) D) CH; 0 co... ( A, ] Explanatio * It is Friedel-Crafis acylation reaction, The succinic anhydride substitutes the para position of methyl group. The methyl group activates the ring towards electrophilic substitution at ortho and para positions by both hyperconjugation and +H effect. & g i 2 3 3 gz zg a g & & z Z g é g Updates & online help through forums are only available to those who purchased this book from the author at hitUpdates & online help through forums are only available to those who purchased this book from the author at http://www.adichemistry.com/ ° plo WO oO. SAIC Note: Excess of AICI, is required since the keto as well as carboxyl groups can coordinate with AICI, Problem 37.5 (IISC INT PHD 2008) The major product in the following reaction is: Oo" "CO "p@* go"co ‘Answer: C Explanation * The intermediate carbocation formed after protonation of eyelohexene can act as an electrophile and attacks benzene ring, + ® Problem 37.6 ‘The major product formed in the following reaction is: > | H 4 Migration of methyl group occurs since it is anti to the OH group in Z-oxime. Problem 39.1 ‘The structure of major product, Z and the overall yield for its formation from the ketone, X, in the following reaction sequence are: & g i 2 3 3 gz zg a g & & z Z g é g 9 NH,OH H,SO, ——_> y______ +z yield = 90% yield = 70% x Hoo Ho ° ° N N. & 80% & 63% & 63% & 80% Answer: B. Explanation: Updates & online help through forums are only available to those who purchased this book from the author at hit * The oxime, Y formed in the initial step is subjected to Beckmann rearrangement to furnish an amide. Eventhough there are two amides possible, the one that is obtained from E-oxime is predominantly formed , since the migration of tertiary group is more faster and populates the reaction mixture with more E-oxime under equilibration conditions.125 Zz Hi n & d HO sn 7 ; ° ze : SN H,0 nH | — — — 3 z Zoxime z a H z € ont, g i wt [yee nod 3 Net é 3 H,0 N. 5 : —— — — > & 3 Zz E-oxime faster migration of, Ss : tert-group g * The yield of Z is 70% of Y, whi 70% of 90% of X. 90 70 Xx os 100 100 in tum is formed in 90% yield from X. Hence the overall yield is jel 3% Problem 40.1 Which of the statements is correct about the mechanism of the following reaction? Me Z a) DMSO reacts with the alcohol initially to give D-o-se which reacts with (COC), Me «(C0 reacts wi the gc atdaty oe) ctnih ent WMO, ® Me ©) DMSO reaets with (COCD, initially o give CIS. which reacts with the alcohol. le @ Me 44)(COCH, reacts with DMSO initially to give CI-O-S,_ which reacts with the alcohol, le Answer: ¢ Explanatior & = F 3 8 3 2 g & z g & 3 g a g é 2 * The DMSO reacts with oxalyl chloride and gets converted to a reactive species, dimethylehlorosulfonium ion Updates & online help through forums are only available to those who purchased this book from the author at ht:/Iwww.adichemistry.com’ Updates & online help through forums are only available to those who purchased this book from the author at it 126 Moor - mH Shee Scr +00, +.60+ 01 H.C cd) a or D HC Dimethyichioro owso | tay sulfonium jon Problem 40.2 (Isc 2009) The structures of the products A and B in the following reaction scheme respectively are: (cocl), i) Hg(OAc), DMSO, -78 °C SS ——_-> a——_+38 ii) NaBH, NEt,, DCM ili) NaOH, H,0 OH oO oO ‘on foo” . 3) OH O 4) & & oor oF Answer: 1 Explanatio * Oxymercuration and demereuration gives Markonikov's alcohol that is oxidized to a ketone in ‘Swem oxidation. oH OH Hg NaBH, co~ oe my oH Oo cH, Hse, -HCI + sto) HyC Gis Sie CH o “ole hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, & = i 2 3 3 gz zg a g & & E Z g é g144 Problem 51.1 (CSIR JUNE 2012) ‘The major products A & Bin the following reaction sequence are: on PPh,, DEAD n- Bu,SnH ——_»> a ——__+ 8 2 -lodophenol AIBN, A :/Iwww.adichemistry.com’ hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, ‘Answer: 1 Explanation: * The first reaction is known as Mitsunobu reaction, which involves conversion of above chiral secondary alcohol into an ether with complete inversion of configuration at the secondary carbon centre. 9H PPh, DEAD ST Fi Da zy Mechanism * Initially, DEAD, diethylazodicarboxylate reacts with triphenyl phosphine to generate a zwitter ionic adduct, which is protonated by the acidic 2-iodophenol to give an ion pair. a be i g : 3 3 8 & zg g é z 2 5 Ss Updates & online help through forums are only available to those who purchased this book from the author at ht145 Php —,_ NN E10,C CO, Et PrP B10,c DEAD (diethylazodicarboxylate) + OH + PhP” PhP oH 1 ener (Geer eee Et0,C CO, Et Et0,¢ —CO,Et ion pair * The diazenylphosphonium part of ion pair reacts with the secondary alcohol to furnish an alkoxy phosphonium ion and thus activates the aleoholic group as a good leaving group. :/Iwww.adichemistry.comv hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, E10,@ CO, Et a HY NN PPh. & \ APO cones PhP Hoos alk * * aN HN, £10,6 CO,Et co,Et * In the final step, the alkoxy phosphonium ion undergoes bimolecular nucleophilic substitution (S,2) at the activated carbon center by 2-iodophenoxide ion with complete inversion of configuration. cr yo + PhsP=O * The final reaction involves free radical cyclization. z i 2 3 3 9 z a 2 g 2 Z z 4 & . g Updates & online help through forums are only available to those who purchased this book from the author at hit146 Chain initiation fini — 24 CN CN CN AIBN (2,2'-az0 bisisobutyronitrile) a {a + +SnBuy con 4 * The tributy! tin free radical abstracts iodine from the benzene ring by giving a reactive aryl free radical that attacks the double bond on cyclohexene ring from the bottom side and thus by pushing methyl group upwards. + NEI :/Iwww.adichemistry.conv Chain propegton IF SS oS? I S T ° 0 creat » - < (e Z E 3 & g & = E & z B z ° Problem 51.2 (GATE 2009) ‘The most suitable reagent combination to bring out the following tranformation is: YOO A) PhCOCIand pyridine B) DCC and PhCOOH B) PhBr, CO and Pd(PPh,), D) EtOOC-N=N-COOEt, PPh, and PhCOOH Answer: D Explanation: ‘JoUNe Jo uo|SssTULIad joy 00g StI AINgLSIp OU OC_“;UIOD-CnSHHIOYDIPE-ALAL * It isan esterification reaction with inversion at alcoholic centre. Hence Mitsunobu conditions using DEAD are suitable for this conversion. * No inversion occurs at alcoholic carbon either with PhCOCl and pyridine or with DCC and PhCOOH or with PhBr, CO and Pd(PPh,),.. Problem 52.1 (CSIR JUNE 2012) Updates & online help through forums are only available to those who purchased this book from the author at ht147 ‘The intermediate A and the major product B in the following reaction are: Zz 3 N. A z % "> ,___+p g NH intermediate g H = 3 eo N Ee Cee cae Crt eee cL S=0 z g NH N g & H e 4 & 3 ° x i 3 3) A= anacylnitrene 4) A= anacylnitrene B= =o & a N r g Answer: 4 H 8 Bp, | e = Explanation: § S _ * Itis Curtius rearrangement. The acyl azide loses dinitrogen, N, to give an intermediate acylnitrene, = 5 which undergoes rearrangement of aryl group on to nitrogen and furnishes an isocyanate. % _ * The isocyanate is attacked by nucleophilic amine group to give a heterocyclic ring, 1,3-dihydro-2H- g | benzimidazol-2-one. z g z g z ea @ Ny? ome 3 ww @ nN A a i 2 N’ NS N =Cs, d 2 <> — (Ni ro 3 5 NH NH NH, iH, 3 g Acyl nitrene isocyanate 9 g g 2 = 2 H g 3 N z g =o & = N & 3 g 3 " g 2 z © Problem $3.1 (CSIR JUNE 2012) z E For the following reactions: A & B, the correct statement is: e : : a Z 3 g Z 2 2 g 3 S a & r 2 5 ry & 5148 cyclohexane is with tert-butyl group on equatorial position. In this conformation, there is a H atom anti periplanar to the Brand hence undergo E, elimination easily by giving cyclohexene with carboxylic group. Br ° Her o Ke { 4 ° ‘opu' 2 Br KOBu' (excess) Br KOBu! (excess) g. a) ——— 8) a § ‘COOH “COOH e 3 3 Ba B 3) both A & B gi E E DAgwves gives cook 9) sive 5 g zg é arom LO cot an 4)both A & B give am 3 = “3 Answer: 2 = g g © Explanat 5 3 F o 0 * However, inreaction B, the carboxylic group itselfis antiperiplanar to Br and hence the elimination involves decarboxylation. ene Problem 53.1 (GUJARAT SET OCT 2011) The major product formed in the following reaction is: CH, & = i 2 3 3 gz zg a g & & z Z g é g NaOet ae “oy EIOH CHy CH CH CH. CH. 1) 2) 3) 4) : ~~ ~OCHs "OCHs CH, CH, CH, CH, Answer: 1 Explanation: * Inthe most stable conformation, the isopropyl group willbe in the equatorial position. The climination of H that is antiperiplanar to the Cl oceursto yield the cyclohexene as shown below. Updates & online help through forums are only available to those who purchased this book from the author at hit149 Zz 20° a Gaon om oH B Aged = AD aS z HC HC g ~ @ 8 CH 3 g z : 2, Problem $4.1 (CSIR JUNE 2012) z 2 Themajor product formed in the following reaction is: = 2 5 3 ° ‘Me,CuLi = 1 = 3 2 Lo. 7 KSA e ty 2) (| 3) 4) Ss Answer: 4 Explanation: * Lithium dimethyl cuprate, a Gilman reagent, is added to conjugated system in 1,4 manner since the ‘methyl group on copper is a softer nucleophile and prefers less polar softer electrophilic carbon ie., 4th 2 carbon rather than the carbonyl carbon, which is otherwise more polar and a harder electrophile. The enolate anion formed can act asa nucleophile and replaces the iodide to give a spiro compound 40 10 Problem 54.2 (GATE 1991) ‘The product of the reaction between cyclohexanecarbonyl chlor dimethyleuprate is: A) OOF CO 'O™ Answer: C Me=Cu-Lme fe and lithium & g 5 3 3 3 gz zg a g & & E Z g é g Explanation: The acyl halides like cyclohexanecarbonyl chloride react with Gilman reagent, lithium dimethyleuprate to 2 give aketone selectively. Further attack on ketone is not possible under the reaction conditions employed. Me,Culi _NH,CI E10,-78°C HO Me Updates & online help through forums are only available to those who purchased this book from the author at hit Mechanism:150 & Me ° ck OH Zz 3 Kee cuetl = Coo A Se _Norku ‘Me B g 2 ‘= Problem 55.1 (GATE 2009) Ee © The major products, A & B in the following reaction sequence are: e e & Zo & 2 Z PAO, CuCl ——H,S0, z 3 ———__+» x + Y Ee O,, H,O, DMF z g 3 3 2 5 F ©, ©) X= Y: D) x= Y: - oO fe ‘Answer: D Explanation: * Wacker oxidation of following alkene gives a 1,4-diketone that is converted to a furan via Paal- Knorr route. wate ossa SI coc tens - Pal, uC _ 180, ea Mechanism of Wacker oxidation & g i 2 3 3 gz zg a g & & z Z g é g Updates & online help through forums are only available to those who purchased this book from the author at hitUpdates & online help through forums are only available to those who purchased this book from the author at http://www.adichemistry.com/ 151 Pd(0) | ‘nucleophilic attack by — water onto alkene Fise | reductve elimination ra Cyt HCl + 2ci ' R~ So j ope cl—Pd—ch, | _CH,OH| aR intra molecular migration of H . -H-abstraction & 4 involving attack of cr | | Gp [= H-elimination cr [ot —e—a cr transfer AN, aq R OH Mechanism of Paal-Knorr synthesis oo 4, HoH oT, 7 26 on tO. 0, os G H Problem 56.1 What is the product formed in the following reaction? Z E 3 & e g & = E & z B z sJoypne jo uosssiuuad inoy.ss Yoog sup aiNqUSIp JOU Og] “AOS AaSTULAYOIPE:ALsUM152 COOH Zz pec 8 Ho. — & z Answer: 8 G00H Ho HOO 3 z \ J vec « > e & Ho. Lm —— zg & & — Explanation: 2 3 * DCC Gicyclohexylearbodiimide) and the carboxylic acid react to forman O-acylisourea E “© intermediate, which is more active than free acid and offers reactivity similar to that of anhydride. z g The alcohol part now adds to the activated carboxylic acid group to complete the esterification along with the formation of stable dicyclohexylurea (DHU). a . Note: Usually this reaction is catalyzed by 4-dimethylaminopyridine, DMAP. g = Ha CoH Dec _ ] " 2 —(Gloyclohexylcarbodiimide) HyyCg-NH_NH-CeHiy DHU i (dicyclohexyturea) © y +0 HO 2 | meee intermediate ii i HyCo-N.NH-CoHs Hy,Co-N C “§ Se, O0 OO HO. y Problem 57.1 ‘The correct sequence of reagents and reaction conditions that can be used to carry out the following conversion a1 H 1)i) KMnO,, NaOH 2)i) AgOAc, L, H,O, AcOH ; ji) aq. KOH 3)i) PhCO,Ag,I,, benzene; ii) aq. KOH 4) i) OsO,, -BuO,H, HO. & g 2 3 3 gz zg a g & & E Z g é g Answer: 2 Updates & online help through forums are only available to those who purchased this book from the author at hit = C153 Explanation * The cis-dihydroxylation of an alkene can be achieved by employing Woodward reaction conditions using AgOAc, I,, HO, ACOH. * In this method, the iodionium ion is generated by reaction between silver acetate and iodine. Thisis added to the double bond from the opposite face of methyl group to give a cyclic iodonium ion, whichis, opened by nucleophilic attack of acetate ion. * Then a cyclic acetoxonium ion is formed by S,2 displacement of iodine through anchimeric assistance, * This intum is hydrolyzed to give a mono ester. * Finally, the monoester is hydrolyzed to furnish a cis-diol in presence of base. rons" Lo r :/Iwww.adichemistry.com’ hy wiogy Stu 91qujeae st yoo styp Jo Kdoo eursi0 a4, Note: * When PhCO,Ag, I,, benzene are used (Prevost reaction), trans diol is formed. * However, cis-hydroxylation is also possible with OsO, and KMnO, but the hydroxyl groups will be antito the methyl group. Problem 57.2 (CSIR JUNE 2012) The major product formed in the following reaction is: 1. CF,CO,H > 24,0" ‘ H ‘OH = "OH = “OH “OH Answer: 4 & : 4 Z 3 3 zg a g & 2 z 2 & 8 Explanation Updates & online help through forums are only available to those who purchased this book from the author at hitUpdates & online help through forums are only available to those who purchased this book from the author at http://www.adichemistry.com/ 154 * Epoxidation of double bond with peroxy acid occurs from the face opposite to the bridge head methyl group. * Upon acidification, the epoxide ring is opened to give a trans diol such that the hydroxyl group closer to the methyl group is oriented cis to it, It is because, the ring opening isan S,2 like process and is only feasible in a 1,2-diaxial transition state. Z E 3 & g & EB z & z B z H 1,2 diaxial transition state oO eon = om ea AS 2 -6 & + = Transition state “ror ve a 2 i Problem 57.3 (SET MODEL PAPER) iS ‘The correct reagents / reactions conditions for the following conversions A, B & C are: : a A =A Ss ‘OH z OH Ez oH z ~ b 7 B & ayaa OH 3 g OH q Loo. e 2 OH e 1) A: OsO,,t-BuO,H, H,0; z B: AgOAc, I, H,O, AcOH 5 i) AgOAc, 1, H,O, AcOH ; ii) aq. KOH AgOAc, 1, H,O, AcOH ; OsO,, t-BuO,H, H,0 ; CF,CO,H, ii) HO OsO,, t-BuO,H, H,O ; B: AgOAc, I,, H,O, ACOH ; i) CF,CO,H, ii) HO OsO,, t-BuO,H, H,O B: i) CF,CO,H, ii) H,0°s 2 3) 4)Updates & online help through forums are only available to those who purchased this book from the author at http://www.adichemistry.com/ 155 Ci) PhCO,Ag, I,, benzene; ii) aq. KOH Answe Explanation: * The syn addition of Osmium tetroxide to the double bond from the face opposite to the bridge head ‘methyl group will furnish a cis 1,2-diol as in “path A”, Note that both of the hydroxy groups are trans to the methyl group. 9 rusesis o—> mn i So ba * However the syn dihydroxylation, as in ‘path B’, can also be achieved by employing Woodward conditions to incorporate two hydroxy groups, which are on the same side as that of bridge head methyl group. IP JOU Og “ALO AnysHUDYSIPE:ALALAYy/sdhyy WHOA, A[UO aIgeHEAL St YOO stip Jo Adoo pourLIO By * Epoxidation followed by protic hydrolysis will give trans diol as shown in “path C”, The mechanism was already discussed in the previous problem. * There is another way of achieving anti dihydroxylation ie., by using Prevost conditions, i) PhCO,Ag, L,, benzene; ii) aq. KOH, as shown below. Note that in Prevost method, anhydrous conditions are employed. a g & z E Ss:/Iwww.adichemistry.com’ Updates & online help through forums are only available to those who purchased this book from the author at ht 156 Problem 58.1 (CSIR JUNE 2012) ‘The major product formed in the following reaction is: ° Z~*"_NaOMe 1» 9 2) CoOMe 3): © 4) * It is Favorskii rearrangement catalyzed by a base. * Initially, the base abstracts a-proton to give an enolate ion, which attacks the other a-carbon to givea cyclopropanone. * Thus formed cylcopropanone undergoes nucleophilic addition by a methoxide group at the carbonyl carbon which is followed by the cleavage of the CO-C, bond. Usually the cleavage occurs so as to give less substituted and more stable carbanion, Finally, the carbanion abstracts proton from the solvent. (ae Meo” \ 9 “o in oO) Meo. > MeO_0 OMe ONS RS =e E ON Problem 58.2, ‘The major product formed in the following reaction hij wiOy fuo a1quILAe st Yoo stIp Jo Adod feUTsI0 oY, & = i 2 3 3 gz zg a g & & E Z g é g157 Zz 3 NaOMe 3 rp ° 8 ca ‘3 2 Ee B cooMe a 8 1) 2) 3) 4) g 2 coome £ 0 0 = | a 7 § Meo g S Answer: 3 E g z ; 8 g Explanatio & = _*Itisa Favorskirearragement ofa-chloroketone with concurrent elimination of f-Clgroup to afford a conjugated ester. § z ou -COOME > {ome age eee ° cr y cl Problem 59.1 ‘The major product formed in the following reaction ‘OH ‘Activated MnO, ‘OH 4 H OH ) ‘OH a) Oo 3) o 4) ‘0 H Hq OH ‘OH Answers > 2 Explanation: * The activated MnO, is selective in oxidizing only conjugated alcohols like allylic and benzylic alcohols into aldehydes or ketones leaving the unsaturated alcohols unaltered. It isa mild oxidizing agent. The selectivity of active MnO, for the oxidation of allylic and benzylic alcohols may be due to formation of a x-complex between the olefin or the aromatic rng in the alcohol and a Lewis acid site on the surface of MnO, The probable mechanism may be: & = i 2 3 3 gz zg a g & & z Z g é g Updates & online help through forums are ony availabe to those who purchased tis book from the author at it158 2 ty Bw g to e ‘OH SO Ho. = Nn=o Nu 5 +7 Mn—OH 8 0 3 OH 3 g z & Problem 60.1 (CSIR JUNE 2012) g © The major product formed in the following reaction is: x Z 3 Br, MeOH E 3 ————__ 5 ao § & 24) Br 2) Br 3) OMe 4) OMe 5 CO a LIS : ‘0 ‘07 “OMe ‘0° F ‘Answer: 2 Explanation * Initially acyclic bromoniumis formed. Its attacked by methoxy group from the opposite face of bulky bromine at carbon adjacent to oxygen, since the positive charge is stabilized by conjugation, & = i 2 3 3 gz zg a g & & E Z g é g Updates & online help through forums are only available to those who purchased this book from the author at it159 Problem 61.1 ‘The major product obtained in the following transformation is: ° BOUL Ts0H, toluene I a 1) o 2) ‘ 3) ‘ 4) CQ Answer: 3 :/Iwww.adichemistry.con’ Explanatiot * This reaction involves acid catalyzed dehydration followed by Nazarov cyclization. * The acid catalyzed dehydration forms a double bond by providing a divinyl ketone. * The divinyl ketone is protonated to give a conjugated system with 4r-electrons and hence undergoes a conrotatory electrocyelization followed by loss of proton and tautomerization to givea cyclopentenone, 102 o on OH H H 4 en lowe Ix>UR4 conrotatory electrocyclization OH OCR, Note: The Nazarov cyclization involves electrocyclization of conjugated system with 4-electrons with 5 orbitals among which one is empty. Z E 3 & g & = E & z B z conrotatory electrocyclization involving 4r electrons ‘JoUNe Jo uoJSsstULIad joy 400g StI AINgLSIp OU OC|“;UIOD-CnsHHIOYDIPE-ALAL Problem: 62.1 (CSIR JUNE 2012) Among the following, the synthetic equivalent for acyl anion is: 1) Nitroethane and a base 2) a-Chloroaerylonitrile 3) Ethylmagnesium bromide 4) Acetyl chloride & trimethyl amine Answer: 1 Updates & online help through forums are only available to those who purchased this book from the author at hit160 * The acylanion isa synthon, an imaginary molecular fragment for which nitronate anions are the synthetic equivalents, SYNTHETIC SYNTHON EQUIVALENT ° NO2 mi A ee aot Acyl anion Nitronate anion * The C-NO, in nitroalkane is thought of as a latent carbonyl group. * The nitroalkane can be used as nucleophiles in presence ofa base as it furnishes a nitronate ion, which can react with an electrophile. Then the nitro function can be cleaved to the carbonyl group in Nefreaction. :/Iwww.adichemistry.conv Z E 3 & g & = E & z B z 2 base { N02) R* No, OW w 9 oy— > |_| ——_ 4, a> Rohe ect? RR, “ir, Nitronate anion Nef reaction * Thus nitronates (furnished by nitroalkane+base) can be regarded as aeyl anion equivalents. Problem 63.1 (CSIR JUNE 2012) The correct sequence of reagents for effe ° pK A 08 —. O ° Ph g the following conversion is 1) a) (CH,OH),, PTSA, A; b) CpaTiCpAlMe)2 (Tebbe’s reagent); c) H,O° ; d) KOH 2) a) (CH,OH),, PTSA, A; b) Ph, P=CH,; c) H,0" ; d) KOH 3) a) CrsTi pwr cr ea g PTSA § ° ° ° OW -H,0 pr HO. Ph Ph Problem 64.1 (SET MODEL PAPER) ‘The major product formed in the following reaction sequence 9 4) Pyrrolidine, PTS Cy 2a 3) Hydrolysis ok ody h ote AK 4 n Answer: 3 & = i 2 3 3 gz zg a g & & z Z g é g Explanation: * It is Stork-enamine reaction involving the formation of enamine of 2-methylcyclohexanone with pyrrolidine in presence of acid catalyst. The less substituted enamine is formed as major product due to comparatively less steric repulsion between pseudo axial methyl group and pyrrolidine. However the more substituted enamine less stable, contrary to the expectation, since the pyrrolidine and methyl groups experience steric repulsion. Updates & online help through forums are only available to those who purchased this book from the author at hit162 * The enamine undergoes further reaction with acetyl chloride, The attack occurs from the opposite fee ofmethyl group. Finally a 1,3-diketo compound is formed upon hydrolysis. less substituted double bond =. + But more stable due to low RN: N steric repulsions 3 G \ 4 CO CHs 8 HC — & gS 8 More substituted double bond 5 H But less stable due to high 2 stable conformer of steric repulsion & a-methyleycionexanone : Oo 3 & z 3 3 E g & 5 = z g & ¢ 3 z Problem 65.1 (SET MODEL PAPER) ‘The major product in the following reaction sequence is: ° 1) (CH,),NH,"Ct, HCHO, EtOH 2) CHL, a oto “oh agh Answer: 4 Explanation: * The conversion involves Mannich reaction followed by Hoffinann elimination. Mannich reaction Hoffmann elimination (CHAK NH(CH)p Hl “HCHO, EtOH OHA Mechanism of Mannich reaction: ‘Joye Jo UoISssUad Moy Yoo stIp aINgUNSIP YoU Og “/AtOD-CnsTUDYDAPE-ALAL Updates & online help through forums are only available to those who purchased this book from the author at ht163 Hach; oH CHy Ve aN H cH, =H CH, iminium ion : e BS HO /H\ HCH HQ HH CHs CHI Q HH CHy g 7 +N No NOCH, i ee eerie ces PhHH CHs Ph HH CHy z iminium ion enol B-aminocarbonyl s ‘compound Z E 3 & g & EB z & z : Mechanism of Hoffmann elimination: Problem 66.1 (SET Model) Choose the correct combination of reagents / reaction conditions; A & B, to carry out the following conditions as well as the final product ‘C’. OH oO OH O pn B c D PBEO*-CO+ C0 1) A=AICL,; B= DDQ; C= Allyl bromide, acetone, K,CO,; D= A. 2) A=A; B=H,, Pd/C; C= Vinyl chloride, KOH; D = AICI, 3) A=AICL; B= DDQ; C = Vinyl chloride, NaNH,; D 4)A=ZnCL; B lyl bromide, K,CO,; Answer: 1 Explanation: * Ring closure can be achieved by Friedel Crafts acylation in presence of AICI, * Aromatization of the ring can be done by dehydrogenation with DDQ to get a-Naphthol. * a-Naphthol is converted to allyl ether with allyl bromide and subjected to Cope rearrangement in the final step. one Jo UOISSsHULIad oy Yoo stIp aINgUNSIp YoU Og “;tOo’CnsTUUDYDIpE-ALALY Updates & online help through forums are only available to those who purchased this book from the author at ht164 OS, ~ oo Friedel Crafts acylation Cope 4 | rearrangement Note: :/Iwww.adichemistry.conv Z E 3 & g & = E & z B z 9 al CN cr CN ° DDQ = Dichloro Dicyano Quinone Dehydrogenation mechanism with DDQ * The mecanism is supposed to be bimolecular. Initially, ina rate limiting step, a charge-transfer complex is formed as shown below = RH, + DDQH’——» RH’ + DDQH, Where: DDQ=Quinone, R= reacting species, RH’ charge-transfer complex * Finally, elimination of a proton from the charge-transfer complex creates.a double bond. Problem 67.1 ‘The major product formed when menthone is subjected to following reaction sequence. ° 7 LDA, THF 10, HCI —__> —__ + —— > y Me,SiCl,-78°C 2) NaBH, 1) 9° 2) 2 3) HOO, 4) OH cr XY 4 ~ il ‘JoUNe Jo uo|SssTULIad joy 00g StI AINgLSIp OU OC_“;UIOD-CnSHHIOYDIPE-ALAL ‘Answer: 1 Explanation: * Deprotonation ofan hydrogen from less hindered a-carbon occurs with LDA during the formation ofsilylenol ether of menthone. * The ozonolysis of silylenol ether cleaves the double bond to furnish a keto and silylester. * NaBH, selective reduces keto group. Finally silyl group is removed to free the acid group that Updates & online help through forums are only available to those who purchased this book from the author at ht165 eyclizes spontaneously to yield a lactone. QSiMeg 0, siMes CY LDA, THE 1)0, wy NaBH, y Mei, 70°0 Y osiMe, oH Fe eat Mechanism of formation of silyl enol ether * LDA, Lithium diisopropylamide isa strong base that abstracts a proton kinetically from less hindered side of keto group to give an enolate ion. * In the next step, O-silylation occurs, instead of C-silylation, since the interaction between hard clectrophile (silyl group) and strong nucleophile (oxygen) is very strong. :/Iwww.adichemistry.con’ hy wiogy Stu 91qujeae st yoo st4p Jo Kdoo feursi0 a4, 7 < ut 7 Me, 9 ° No ff OSiMes -PO.NH | 1) Ry cy wesrel Problem 68.1 (GATE 2012) Identify the most probable product in the given reaction: ©, | Benzoyl peroxide —— OOH ‘OOH A) 8) an) >) OOH Answer: C Explanation: & = i 2 3 3 gz zg a g & & z Z g é g * The hydrogen on tertiary benzylic carbon in Cumene is highly reactive and can be easily abstracted by phenyl freeradical to give a tertiary cumene radical, which further reacts with dioxygen to give cumene hydroperoxide radical. ‘The hydroperoxide radical abstracts a benzylic proton from another cumene ina chain propagation step to give Cumene hydroperoxide. g Mechanism: 3 Formation of phenyl free radic: 2 & online help through forums are only available to those who purchased this book from the author at hit9 a pr—X ¢ of = og 4. Np ¢ Ph oO Oo Chain initiation: a H3C-C-CH, H3C-C-CH, Ph ——> +PhH Reaction with dioxygen: °° H3C-C™CHy Hyc-C-cHy :/Iwww.adichemistry.con’ Z E 3 & g & = E & z B z Chain propagation: °° 4 ot I fl I 7 HjC-C-CH, HyC-C-CH, — HjC-G-CH, HxC-C~CH, Problem 69.1 (CSIR JUNE 2012) ‘The major products A and B formed in the following reaction sequence are: ‘JoUNe Jo uo|SssTULIad joy 00g StI AINgLSIp OU OC_“;UIOD-CnSHHIOYDIPE-ALAL Updates & online help through forums are only available to those who purchased this book from the author at ht167 °, = Cree C= —~ + a —__> 8 Pa(PPh,),, KPO, 1) Az Ornsy B= Cn ‘0 - : SAN 2) A= Ory e Or 0 aa- fo B= \ I om) 8 . ‘og: Bu 4) A= B= ry ‘Bu Explanation: * The reaction sequence involves the preparation of vinyl boronic acid followed by Suzuki-Miyaura coupling reaction using tetrakistriphenylphosphine palladium(0) catalyst. * The first step involves the syn addition of catechol borane to the triple bond to give atrans vinylic boronic acid. Or 8 Of * The boronic acid is made to react with a vinyl iodide in presence of Pa(PPh,), in basic medium to cary out coupling. The first step is oxidative addition of vinyl halide without any inversion in the configuration. Thus formed Pd( I) complex reacts with boronic acid in presence of a base to achieve transmetallation, The final step involves the reductive elimination to achieve coupling. IP JOU Og “AUIOD ALNsHUDYSIPE:ALALAYy/sdhyy WHOA, A[UO aIgeHFEAR St YOO stIp Jo Adoo peurLI0 oy a g & z E Ss Updates & online help through forums are only available to those who purchased this book from the author at http://www.adichemistry.com/168 PPhy ‘But oy PPh, ca oxidative addition Bu" \ Phg reductive elimination, :/Iwww.adichemistry.comv hy wiogy Su 91qujeae st 00g stIp Jo Kdod feursi0 a4, Oe Cres oO Problem 70.1 (GATE 1991) ‘The reaction of potassium phthalimide with ethyl chloroacetate followed by hydrolysis results A) glycine B) alanine ©)leucine Answer: Explanation: * The reaction of potassium phthalimide with ethyl chloroacetate leads to formation of aN-alkyl phthalimide, which can be cleaved hydrolytically to generate glycine, an amino ai & g i 2 3 3 gz zg a g & & z Z g é g ° ° ° cl H,0° H,N- Wk eo Na on Vo EO ~\=0 EtOH OH HO O 0 Eto oO alycine Updates & online help through forums are only available to those who purchased this book from the author at ht169 Problem 71.1 Oxetanes can be prepared by photochemical reaction between aldehydes or ketones and. . A) alkenes B) alkynes ©) ethers D) lactones Answer: A Explanation: The photochemical [2+2]-cyeloaddition of carbonyl compounds and alkenes to furnish an oxetane is termed Paterno-Biichi reaction. The carbonyl compound normally absorbs light to furnish a singlet carbonyl compound which is usually converted toa triplet state by intersystem crossing (ISC) and then undergoes [2+2] cycloaddition with the alkene. :/Iwww.adichemistry.com’ Z E 3 & g & = E & z B z ROR ROR R' Singlet Triplet 4,4-biradical Problem 72.1 The major product formed in azidolysis of the following epoxide will be: H : NaN, Oo jy MeOH-H,0, NH,CI 1) OH 2) Ny 3) OH 4) OH sn, so shy ws y Ny ‘Answer: 4 Explanation: * The azide ion attacks the third carbon from tertiary butyl group in axial manner from the opposite side of bulky tertiary butyl group. However, the attack of azide ion at 4th carbon from the tertiary butyl group does not occur, since the ring opening is an S,2 like process and is only feasible ina 1,2-diaxial transition state, ‘JoUNe Jo uo|SssTULIad joy 00g StI AINgLSIp OU OC_“;UIOD-CnSHHIOYDIPE-ALAL Updates & online help through forums are only available to those who purchased this book from the author at ht1,2-diaxial TS Problem 72.2 ‘The major product formed in the following reaction P nProK :/Iwww.adichemistry.conv Z E 3 & g & = E & z B z A) Hee on CS Answer: C Explanation * The propoxide ion attacks from the opposite side of epoxide ring at less hindered carbon, 4 CHs nPro’ } wy Problem 73.1 (CSIR DEC 2011) Match the following starting compounds with corresponding products in photochemical reactions. Joye Jo uoISssHULIad Moy Yoo stIp aINgUNSIp YoU Og “/AtOD-CNsTUUDHDIPE-ALALY Updates & online help through forums are only available to those who purchased this book from the author at htim Fi Starting materials Products e 9 ~_—e" E -AAK 7 b 8 4 3 . © ) 2 px 2 i z g a try : Bn bn Z 3 iil a aa & oy : = OH i a 2 2 Die 3)id ite iia dive ita ifi-d Answer: 1 Explanation: * The starting compound (i) undergoes Norrish type II reaction to give a cyleobutane (e). It involves abstraction of ay-hydrogen by oxygen of keto group to give a biradical that subsequently forms cyclobutane ring. LH 0. hv S AWK yy By Wye * The starting compound (ii) undergoes Norrish type I reaction to give product (a). Initially a biradical jis formed due to homolytic cleavage of bond between carbonyl carbon and the a-carbon. Then a B. hydrogen is abstacted by the carbonyl carbon to give an aldehyde group along with the formation of double bond. 9 oO ° 0 7 by A adr ees ee thy — H =<" v : : * The compound (ii) isa trans alkene that undergoes photochemical cis-trans isomerization reaction. Initially the alkene is excited to S, state involving x ----> x* electronic excitation. In this excited S, state, the double bond character is lost and the bond is free to rotate. The, state is relaxed to S, transtion state by internal conversion, which may decay to either trans or cis ground state, yo tv “itera trans r Ct ae ind stat ground state mae PEaHion eee ground state OH : : 3 9 3 a 2 z z 3 g & 3 Updates & online help through forums are only available to those who purchased this book from the author at http:172 4 Problem 74.1 (CSIR JUNE 2011) & ‘The major compound, X, formed in the following reaction exhibited a strong absorption at 1765 cm" in the IR spectrum. The structure of X is: E OH g OH & z ex & 8 CH,Cl, g g OH L OH 5 ? & § cory CO “Cy ee "oy g 3 3 E 3 J 5 i ‘Answer: 4 l4 g “= Explanation: e * The strong absorption at 1765 cm! indicatesa cyclic ester or lactone. Hence it isinteligibly evident 3 that PCC oxidized above 1,4-d 5 to ay-lactone. The reaction involves oxidation of primary alcohol to aldehyde by PCC to give ay-hydroxyaldehyde that equilibrates with lactol,a cyclic hemiacetal, which undergoes further oxidation to ay-lactone,a cyclic ester OH Oo oH oH 9 9: aor Pcc. ‘CHO Pcc CH,Cl, CH,Cl, 1,4-diol ‘hydroxy aldehyde Lactol Lactone Note that PCC, like PDC, can oxidize an alcoholic group to a keto group only. Further oxidation to carboxylic acid is not possible due to anhydrous reaction conditions. Problem 75.1 (CSIR DEC 2011) ‘The major products A & B formed in the following reaction sequence are: & g 2 3 3 gz zg a g & & E Z g é g ° 41) LDA ( 2 equiv. ) 1) AIH, n> equiv. H,O° Yat ») Hs ou OH ou’ ° ; AAs 7S OOOH co 2) A= 7S 000CHs oe Z 4 ZA 4 ou OH ou’ ° .COOCH. COOCH. Za A 2 A Answer: 2 Explanation: Updates & online help through forums are only available to those who purchased this book from the author at ht * LDA, Lithium Dilsopropyl amide is a bulky strong base and hence selectively abstracts a proton173 from less hindered a-carbon to give lithium enolate, which isa good nucleophile and substitutes allyl bromide. . af an, Au uy ou RNY P| roy CoocH, IK -COOCH; KOK coos me RIL" =LDA Che Note: LDA isa good base but a poor nucleophile due to bulky isopropyl groups and hence it cannot attack carbonyl carbon. :/Iwww.adichemistry.con’ * The above product, A, as such in the enolate form, is reduced with LiAIH, to reduce ester group to primary alcoholic group. Z E 3 & g & = E & z B z ou" Ou COOCH; —_LiAIH, OAH, Note: If‘A’is first treated with water, to convert enolate to corresponding keto group, this is abo reduced to secondary alcohol with lithium aluminium hydride. In that case, the correct option would be option-1 Problem 75.2 (GATE 2004) With respect to the two reactions shown below, the correct statements about their stereochemical nature is: [where LDA =LiN(Pr,)] to Pho 4) LOA i) a oe x © ay "PrBr A) the reactions are stereoselective, because P and Q are the same B) the reactions are non-stereoselective, because P and Q are the same ‘JoUNe Jo uo|SssTULIad joy 00g StI AINgLSIp OU OC_“;UIOD-CnSHHIOYDIPE-ALAL C) the reactions are stereoselective, because P and Q are diastereomers D) the reactions are enantioselective, because P and Q are enantiomers Answer: A Explanation: * Both reactants give same enolate ion due to abstraction of a-hydrogen. Hence same product is formed. The alkyl group attacks the enolate from the opposite side of bulky isopropyl group. Updates & online help through forums are only available to those who purchased this book from the author at hit:/Iwww.adichemistry.com’ Updates & online help through forums are only available to those who purchased this book from the author at ht 174 preferential attack from the top in os Br Pr ee a fine ui" we enolate = Product * These reactions are stereoselective since both isomers are giving only one diastereomer preferentially Problem 76.1 (CSIR DEC 2011) aa appropriate reagents A and HO. OH oy orm BH,Me,S 2) A=BH,Me,S;B H,.MeS 4)A=BH,,I the following reactions. Answer: 3 Explanation: * LiBH, selectively reduces ester group to primary alcohol, which lactonizes with the acid group. However remember that, its analogue NaBH, can neither reduce ester nor acid group. The observed reactivity of LiBH, can be attributed to the increased Lewis acidity of the Li' ion which confers increased electrophilicity on the carbonyl group. Another reducing agent LiAIH, can reduce both ester and acid groups. * Whereas BH, Me,$ reduces only carboxylic group to primary alcohol. During the workup, the ester group is hydrolyzed to free the carboxylic group. This wil further react with alcoholic groupto give alactone, ‘Note that the lactones obtained in above two rea tion paths are enantiomeric to each other. Problem 76.2 The appropriate reagents A and the following reaction sequence are: 3) A=Sn/HCl; B= LiAlH, Sn/HCl; B= NaBH, Answer: 2 Explanation: Z E 3 & g & EB z & z : Joye Jo uoISssHULIad Moy Yoo stIp aINgUNSIp YoU Og “/AtOD-CNsTUUDHDIPE-ALALY175 * NaBH, selectively reduces only the carbonyl group to alochol. It eannot reduce nitro group. Finally Sn/HClis used to reduce NO, group to NH,, * LiAIH, can reduce both carbonyl and nitro groups. However the reduction of nitro group does not yield amine. Instead it will give an azo compound in appreciable amounts. * The cyanide ion acts as a good nucleophile and attacks the aromatic aldehyde. It is followed by & transfer of proton onto oxygen atom to give a stabilized carbanion. This step is facilitated by electron 3 withdrawing nature of cyanide ion. The carbanion attacks non aromatic aldehyde followed by loss of cyanide group to give the final product. ‘Joyine jo oI Problem 78.1 The major product in the following transformatio Zz 3 z g Problem 77.1 (GATE 1998) g ‘What is the product formed in the following reaction? 2 z e $ : i § ae 5 2 bon, = g Solution: g 3 z £ 5 z = nfo z q (~~ s ™ y [ H 24 [3 wd-cn HO@CN ia : z = HO: o 5 é cN NO2 Z ar =— =— 2 8 z 2 2 OCH; OCH, OCH; OCH, NO, 8 3 3 4 2 g \ ci 4 4 3 Z Ae on °. aa S 2 2 i = — Zz = z 2 OCH, NO» OCH; NO, e 2 z 5 Z & Explanation: = E_*Itiseross coupling benzoin condensation berween two dierent aldehydesto giveana-hydroxpketone & (abenzoin). Only the formation of major product among the four products possible in above reactionis"2 @ shown, 5 5 g Z 2 é z S 2 2 5 ry & 5176 4) Buli 2) ono) <~*s0,Ph ————> 3) Phcocl 4) NalHg, MeOH 1qeeAk st Yoo stIp Jo Adoo peursiz0 a4, wy abr OX onan ran Explanation: * This reaction sequence is called Julia-olefination. It starts with deprotonation ofa sulfone at adjacent = carbon of sulfarby using a strong base like butylithium ora grignard reagent to give an organometallic & species, which is then added to an aldehyde to furnish a B-hydroxysulfone, The B-hydroxysulfone is esterified with an acetyl or benzoyl group, usually in the same reaction vessel. z ‘Thus formed ester derivative is subjected to reductive cleavage by using sodium amalgam to give an E- = alkene selectively. fraiche con acidic proton 7) i Buli YEN ‘SO,Ph - PhCcoci NalHg ——> nos SS a sS Ss in situ bo MeOH esterification 4 Ph The E-selectivity ofthis reaction ean be attributed to the formation of less sterically hindered carbanion in which the bulky groups are arranged as far apart as possible. ‘Joye Jo UoISssiUIad Moy Yoog StI aINgUNSIp YoU Og “/AtOD-CnsTUDKDAPE-ALALY Updates & online help through forums are only available to those who purchased this book from the author at hit177 Mechanism of reductive elimination using sodium amalgam Na’ ph dianion with a lone pair on sulfur :/Iwww.adichemistry.comv Ph The least sterically hindered conformation of carbanion Problem 79.1 (GATE 2004) In the following three step transformation, the correct combination of products P, Q & R are: gH BFeEO LDA Raney CHO + yg SH_ > p ——»> gQ ——> R “OLPOD OV O81 Of OO” O48) Qo Q OO OC O77 ‘Answer: D Explanation: * Benzaldehyde is thioacetalized with ethane-1,2-dithiol in presence of lewis acid, BF, and gives a 1,2- feursi0 a4, | Ag,0 NAN aor hy 1) Me O 2) Me O 3) Me 4) Me pr bom pr ome wr Pr ome Answer: 1 me 0 g Explanation: e * The diazoketone undergoes Wolffrearrangement in presence of Ag" ion and light to givea ketene with © the retention of configuration at migrating center. The ketene reacts with the solvent methanol to give a 2 methylester. Me Me mm mem AE 3 Wolff rearrangement with retention of, configuration at chiral migrating group 2 3 Be 2 sJoypne jo uosssiuuiad inoy.ss yoog sup aingusIp OU Og] “AO