(nee e eee eeeee Reactions Abcohoes @ Acid-Base Properties of Alcohols @Aicoxides as Bases & Nucleophiles @ Acid- Catalyzed Dehydration @EL Dehydration with Pods & pyndine @ Reaction with Hydrogen Halides CH-%) @Alcoha Activation via. Sulfonyl Esters @ Conversion to Chlovides with SOclr , PCy; ac PCs ®@ Conversion to Bromides with PBra, PBrs3 or PPh2Brs @ oxidative Cleavage of Vieinal Diels with HTO4 ® Oxidation of Alcohels Code: ATIEEREACTIONS OF ALCOHOLS 4. Acid-Base Properties of Alcohsls R-of == AS+ H® — phaz te te 18 @ R-OH, == ROH +H? pka= O to -2 2. Alcoxides a8 Bases %& Nudeophiles NoH - >on ——_ Le R-X Dn ~5-% Williamsen Ether Synthesis C8n2) en e~ Basic OH OC => use for Elimination Reactions (2) 3B. Acid Catalyzed Dehydration HeSOq > El mechanien Ay a Axe 5yees oS OH 4. EL Dehydration with POcls & pyrdine Pola E2 mechanism ar P or Gt on PO 6. Reaction with Hydrogen Halides CH-%) Ar Ace, Se Sut Cwith posite c® rearrangement) + Hed on H-&ec AA Aw SuZ mechanism 1 IH +H,O © Alcohol Activation via Sulfong! Esters >on BO Pe, Aor x or Mech © Ss elimination Reactions or TFC Substitution Reactions Ashiasis Tyg Sov Code: ATIEE3. Conversion te Chlorides with SOclz , PCla; ar POs ohiw Aon Soda Pe A>nw + SO, + HCR Sn2 mechanism or Pola or HaPO3 Seen Pdls is used OF PCS or HaPQ, When Pcs is used B. Conversion to Bromides with PBra, PBrs 3} Or PPh2 Bry Pra, PH Aon Dre SwZ_ mechaniem or PBrg or PPh, Br, % Oxidative Cleavage of Vicinal Diols with HFO4 Nw Ay G&G + HIO, OH 4D. Oxidation of Alcohds Prienaray alcohds eS carboxylic acids J Lo} AE {ders Oxidation CGrOg , H2zSQy on OH or HeCrOq , or KaCr2O3 , H2SPy ) {o] Pee or PDC 3 Primary. aes > aldehydes | soon: “y & 1 DMSO, tans on SW =o ‘Dess- Martin : ots D. 77 Sore. Secondary. alechds 2s ketones FeO One oO} AY — Ar Ang. Oxidation method én fo) including, hypachionte or TEMPO oxidation Selective Giseten of benzyic & alge aleshols with MnO aS MnO2 aS T MnO, aan Cayic ET on “a «Er HH OH Ashiasis Tyg Sov Code’ ATIEE4, Acid-Base Properties of Alcohss, abu Alcohols can be Brgnsted acids & dissociate in solutions Ss ® R-OH == RO + H “Typical dissociation constant of aleshols alcoholate- is mall: Alo to 48 Elechon- wit “Sorgen of Groups & Resonance eens of the negative charge on ox The alcoholate anion ineveose the dissociction constant => Oe ail alcohels more acidic: cr? A ‘OH OH ot at a ar more acidic Alcohds can be protonated by sbong acids such a5 HBr, HT, H2SO,, ete, <— oe @ 6 8 R-OH + H& == R-OH, — Typical pka of Protenates alcohals "easing \ Ob-2. gree Substitution or Elimination Reactions 2. Alcoxides as Bases & Nucleophiles, Alcohols can be deprotonated with strong. bases 40 give alcovides R- f+ Nati —* RPuPs Hz Ga) ~ is removed from the reaction mix or @ ¢ => 400% conversion from alcohel 2R-Of + 2K —>2RS e+ 2 @) te alcoxide Alcoxides Calecholate anions) are beth basic & nucleophilic Se 5 8 * oe HO CHAO CHA CHO H-c-& Hac -S smaller 2pecies on \ cater Species S Basic wae Smailer non~sterically hindered 4°82" alcoxides ais Sw2 products with Primary. ae na s Williamson Ether Sthedis) DAS BLA <8 A>~~o~ Other combinations alcoxides : a halides yield torical e2 ete’ Bavtead Cahates bases) & Hefnonn Club Dice & Ashiasis Tyg Sov Code ATIEE3, Acid-Cotalyzed Derydration (El mechanism) hwy toa H-bransf tt Le tt - -c- -c- \c=ac% -—c-c- —— 0-H 0 Nea’ voy pe T AY disse. WO ae » Ho >QH HSOH SY 4 product or HaPOy HScy Since reaction proceeds Qccording. te Gl mechanism, carbocationic “Le ace possible + 8, Su, AS hentia GEL A Gp ax. L/S aiff N-@® Heh El reactions typically. produce Zaitsed veo” Y) product Cost thabe Gee cond fiom alll or HO: feme alternatives) : SS Presite double bonds A bansh sr CElimi nation Os dre cr- ar most skate Crmost Hofmann Zaitsey substituted) double Product Produc bond. 4, E2 Dehydration with Pods & pyndine (EZ Mechanism) 14 tot ol —Ct-¢c~ -¢-¢- —— > —Csc~— —> Seach 4 \ 95 4 le ce ihe ° 7 :OH S SY Cg \e PQ nt b AN N \ avid ON 7 Reaction offers a direct gentle dehydration Alcohols in basic conditions lows 2 mechaniem” & weet oe the Zaitsev product igtrent the eat & earcngennt: wee Sh SES ake sero Product Ashiasis Tyg Sov Code’ ATIEE5, Substitytion Reactions with Hydrgen Halides CH-X) R-OH + HK —> R-X + Ho % Be, T C Mechanism Cori alcohols) Ron | Mechanism a; tna ° P H- Be H-transfer t( . Sad DN 4 AA, leaut Ol STOW eau 2 | Su2 oc Sut * & grup 2 Sut Primary. leaving group cannet | Nucleopaite dissociate bie would give a Attack very. unstable primary, carbocation = eeackon nket 4 according ae + H20 Example: te SZ mechanism. ° ”“~~on xii pet HO 95% yield weak nucleophile in protic conditions => Q Lewis acid tn SNZ reactions with HCL: CO 2nes, ON teitor taung, goup ban 8 i gp grup "i ) formed in harsher™ conditions Chigh c: Note: cf is sufficient, cotalyst is used o™ 26H 2nd, — When Sn2 reaction with HX is Q Conserted leaving group dissociation with hydride shift may occu WAY oe H-bansf rely, LG dissociation Te Oe eg OH pte 2 yag-n-shift eo Rete “This process is only favored when the newly formed carbocation [rucesrite fs resonancely, stabilized Ceg. allylic or benzylic. positions) Attack Mechanism Csecondary, & tertiary, alcohols ) me be | LO@-diesec. ° Ay. Bf Ap ASE LE crcontone revo H-&r Cox, HW ® wall happen if a new 2 i moe stable than tre @ \2-H ont origina carbocation 2. 2 BC” & more shale SE Nucleophilic a thant ce Attack eR a - SS A HBL Racemie , Mixture Code: ATIEE@ Alcohol Activation via Sulfonyl Esters ohiw ° oO dine, w R-OH + RS £8 R-0-S-@ + Ha reacts w poo! leaving, ° = 1b firm a group geod leaving. grup Commonly. used sulfory chlorides R-SO,C: of Nate: gyrtine ED w Ts, " a s “S commonly. usec CHa-S- Hac Y-S-c2 FatS- ee ae a Waid solvent 6 ° 6 in this reaction. mesigl chloride | chloride tify! chloride. “ 2 Pe ian mesylate ester tosylate ester briflate ester t g t CHsS-OR Hat -S-OR Fxc“S-OR } © Residue from tre alcohol Mechanism: RD jucieophilic Ss ~~ bn oben, Maceo, WA BOSS cy, butane) "oh aid 1 | Leaving, Group Gimination ° W oP a temele KS cH, butyl mesylate, (ous) = Exampes: Rind) Pyridine, Cease) Sutsttut Sn or Sw2. or “reco oe kstitution C Sut or ) “ Re - Elimination CEl or 2) on ao 2 ee Askari Tyagi Sov Code: ATIEEConversion of Aleshss to Alkyl Halides with SOct, ; Porgs or PChy! 2 R-OH + Soc, = Rcd + so, + Heo, Reacts w py to form satt SOA ——~On TO usual wi treating, this ou ee e@ ~ eeackion °e f 3 ¢ Sede TON when oy Enversion of —_— eR a with Pye configuration S FH F Swi when ap Retention of —_— OO reaction is done configuration neat] Neat Cwlo sclvent) Swi is an advanced topic & is usually nc covered in an Untroductory, omanic Chemisty Se SO ep Leaving. Group wg ee Eliminhtion, Cen 35 HO:# tt li 7 Nucleophilic. i AKA Attack “~~ eR cl al i Sn2 Mechanism: Ve ot S48 ii ea H- bransfer Heb og A = Leaving Group Elimritiotion r Sie ” aN NZ a N. FO SL geso SO ~~ Secondary, alechols occasionally give carbocations => i=) a Carbocatenie, rearrangements “are possible . Sni_Mechaniem: Sut stands for ipso substitution Cfrom the same side) The first two steps are identical to Sw2 mechanism. ° 4 OH a oy 1 OW seq Sa 2 ~AK,. 8B 5 Sree =~. as) NA Steps A Retention of configuration Ashiasis Tyg Siv Code’ ATIEESut R-OH+ dls Cor Pdls) R-C2 + derivatives of phosphorous Mey Phosphoric acid Examples: Pda oH ooo Pa f Pls Le S82 mechanism =7 ~~ — inversion af confyurarten Mechanism: CO a 4? \ On HO: He Pry oon 2 SPQ _Nudeopritic, GP H-transfer, eo mm oh, © Fttack ~HK aN Nucl ihe. Pyridine oe this reaction Stboen | ming O~pcod leavi ve mate iors re aie? P. sep. Px Recekion with Pig is mechanisticaly J Su2 8 aS Bimilac to fhe reaction with PCla. —_t- 3S ce 8. Conversion of Alcohols te Alkyl Bromides with PBrs, PBre, or PPraBrs 2 Br R-OW + Pere Ee Q-Be + denwarives af Cheschewus or or PB | PY phosphoric acid o PPh, brs Reaction is mechanisteally, identicat to the reactions with PCa & 5 Capes through tre Gime. mechaniste steps). Exampes: _ Pra OH non Be ? PPh. la SNZ mechanism => —_ = AK inversion of configuration Since both GP & @B) ave SN2 in nature, Drey are not very. usehd er converting, 3 auicohols into corresponding “alkyl halides ~~ oH Be Code: ATIEE4 Oxidative Cleavage of Vicinal Diols with HLO4 ot HX \ -c-c- o C=O OFC + HTOS , 4 Penodic *~iodie acid OH OH ‘acid Carbone compounds —_——_ Caldehyde and] or Vicinag diol ketone ) Examples: CH HLOy me _ —— IOs om Co, oe a 1 gh + Hits 3 Similar ucts cai Can be Obtained in O reaction With KMnOy , but. as KMnOy is a er oxidizin ) unwanted side reackdns Concluding, furber @ dations) mnt Soecur. Mechaniser: HO oH 2 a i ili i >Te 1 O oO 2 | H-tansfer Fon r O~ LA Cc Nucleophilic r Sth be So Attack’ an Io TY" oO! H KO H -transfer | ° oH oO ° OH fer 0 oO Co SE ue \ pic > exsate Qedaliye ~ ce Ty, S70 Fiminark O71 2° \ min’ So cece wires te vicinal diss to be spaciall ose, Cgauche or rmation) for One reaction to proc nosy Ashiasis Tyg Sov Code’ ATIEE40._Oxidations_of Alcohals * Primary. alcohols fol, Carboxylic acids a-cy-on 2, ge 2 OH This reaction is often called Jones oxidation and it is done with CrOz + H2S0q or Hz CrOy Common among au these reagents is Cr@) or K2Cr203 + H2S04 Exames: So CrOx Aon H2S0q Ao ©. t HO ><> OH HeCrOu Hoon ones. oxidation will oxidize all nprotected alcohols to correspon - oH Rr d cbony’s i Caldehydes Cr K2CraO3 oy on Keltnes) oacids OO Ho i, at Oxidative 4 Bo “Etimnatin AVRo cf on oO H2S04 Mechanism : o Sy Nucleophili § 5 Neu AQ Atkack Ana i, OA i g os H-transfer y Protenated C0; H20: . é id e HON, OF During the first oridation 4 Be actin of oy! Oo Of Ve cin the Second oxidation step , carbon iS Oxidized Do “e/g, fiom the Oxidation state + te +S losing 22. AshiaaiTypgi Si Code: ATIEE (LL alcohol is oxidized +A G - OM Oxidation state —4 to +4 \ sone Jing AZ while Cr goes from HH , +0 es gaining, 220 fe . Ara Oke ° AQ Nucleophilic ot Adz 3S nee OH 3 DALES on MH H2O: \ 5 4 Sy OH F tudeoshitie ft borsfeg 2} Con DKA8 Rot attack ANG, eng g Oxidative, 4c geminal dice 07 GR 6 Lee eet R_OKe 4 z 8 9g 0% Primary. aleohds 2b aldehydes selective methods) R-cH-on 2 Re Method 4 Cnost commeniy taugh’) | Method 2. Method 3 PCC = pyridinium chlorochmate | Swem Oxidation | Dess-Martin a Oxaly\ Periodinane So Se N 3) 1 SS Cr = Ben b-c-2 eg Chloride o np ° _ dimetny! il PDC = pyridinium dichromal DMSO = i Pyridinium di chomate sulfoxide Na! Etan = trethylamine | ALO a v tT © Ory Bb cp-0-te— 28a Be-og-s oO Examples: Pee AK Ao Either of the three methads from OH DM “solvent aowe will oxidize all unprotected swem alcohols in the molecule t the Ho OH ——> 07 >X no further Oxidation occurs & reacton See at me oxidation Only. oui. an aldehyde oO Ashiasis Tyg Sov Code’ ATIEEMechanism of the Ewem Oxidation tne me ie. m, \ou es KARP X28 9 2 9° 'S=0) —, 's=0, <— s-o U5 Ne y Se 7 Ay oO dirmethyl\chlorosulfonium ion Step 4: formation of | that réacts with alcohol seer NS eine DY BG , ine met eb, imethyl chloro’ ium iON re ee ANH WP ine DAY OF we : Dro ki Hes oe i Step 2: oxidation of alcohol (2s, YY i Oxidative | 4 Ss base My Smeg ~ Axo BSS ‘Elimination DOB YF ine Note: Swem oxidakon i usually performed at Cow temperatures ClooC t -38C ). Mechanism of’ Dess-Martin Penodinane Oxidation Dess-Martin Oxidation is usuatty performed in DOM CCH2Cle ) or Chloroform CCHCls) at room teblpbrature.. Ashiasis Tyg Sov Code’ ATIEE* eet alcohds, fol Ketones RY vt to] RN aon R~ Seconda, aleohds can be oxidized to ketones Using, ony, Oxiderion method tke : Oxidation vw Pec & PDC w oxidize Primary alcohols to aldehyctes { Swern Oxidation but wort oxidize aldehydes further to Dess-Martin Oxidation v~ J Carboxylic acids tke other methods Fe poctiovite Oxidation Vv MeO ~catalyzed oxidation w Green chemishy. cnvices Mechanism of’ Hypochlorite Oxidation of Alcohsis. Ca se H-bransfer He ye 8S wk tpn hn T wry ao SR Nudleophili OYOUS. “usualy Me ic acid so HaPOy Attack =/™, : 4 R Hel A R 4,0: Y NR _7 7S H-tvanaf U2 _@ Np omc —— ba, Set ose +e oe ce Pros: green chemist Cons: H2O as a soluent => poor ealutildy of imple rea, oganic mel 20 Solvent Acidic. conditions mag cause unwanted ide reactions. Mechanism of? TEMPO- Catalyzed oxidation (TEMPO, KBr} Noel; Dem, HO; 0°C) Heo CES Bok Lae 4 NS - _ a S, “ ~He oR 4,0 4 xe TemMPo= 2.2, 6,0-TEtraMethy!Piperdine= “Ae Oxy OH nS) o=c NWR oH R Ashiasis Tyg Sov Copa ZATIER,Alechal Oxidation Methods ohiw Qjones Pfr | Swern | DEM | TEMPO adaton Primary, acid | aldenyde | aldehyde | aldenyse | acic Secondary.| ketone | Ketone | ketone | ketone | ketone Tertoy | NR | N@ | NR NR NR ~ Chee Of alcohet Product of the oxidation reaction %* Selective oxidation of benzylic & allylic alechds with MnOz MnOz will Selective oxidize ailytic & benzylic aleshds to the pope while not ci wits Qny, other —OH moe Kee molecule "o oe Sooo OH Oo I 2 OH Mar ayo lay —- OK OH O CH Mechanism H-branef. an —- «zn eu “Os mn = 6 Acetone. ~> e Sst Seventy Ng oma Intermediate 6 i Ashiasis Tyg Sov Code’ ATIEE