Problems 141 Substitution at C(sp?) usually occurs by an Sw1 mechanism under acidic con- ditions; the $2 mechanism is operative at C(sp*) only when the C(sp?) is 1°, the nucleophile is very good, and the conditions are very strongly acidic (However, substitution at heteroatoms such as $ and P usually occurs by an Sy2 mechanism under acidic conditions.) Substitution at C(sp2) normally occurs by an addition-elimination mechanism under acidic conditions. Electrophiles add to nucleophilic C=C a bonds, in- cluding most arenes, and nucleophiles add to C=N, C=O, and electrophilic C=C ar bonds. Arylamines can undergo substitution of the NH group by a diazonium ion mechanism, ‘Under both acidic and basic conditions, a carbonyl compound is elec trophilic at the carbonyl carbon and nucleophilic at the a-carbon. Similarly, under both acidic and basic conditions, an a,8-unsaturated carbonyl compound is electrophilic at the carbonyl and B-carbons and nucleophilic at the a- carbon after a nucleophile has already added to the B-carbon. Carbonyl mech- anisms differ under acidic and basic conditions only in the protonation and deprotonation steps: under acidic conditions, nucleophilic addition is always preceded by protonation of the electrophile and followed by deprotonation of the nucleophile. PROBLEMS 1, Rank each set of compounds by the ease with which they ionize under acidic conditions. (@) Me Me Me rs vor moar w/e Me Me 6) a cl a On Me Me © AL AY AAn on id) Com or mG ore @ mc a, ac anc i NMe oT1423. Polar Reactions under Acidic Conditions (f)AcHN, or MBN ACO, (g) px ‘on 2. Indicate the major product of each of the following reactions, and draw a rea- sonable mechanism for its formation. o Cpe aa Pb ©) cr CHCO2H Ph ‘OH cat, TSOH © ‘benzene Ho. @, Acow — a © bon aa 10) © Cy-on HoH en OH on cone. HB: (g) Ot —. (hy) npn SL 3. When B-caryophyllene (1) is treated with sulfuric acid in ether, a large assort- ment of products is formed. Initially, after 1 is consumed, compounds 2 through 4 are the major hydrocarbon products. As time goes on, compounds 2 throughProblems 143 4 disappear, and compounds 5 through 9 appear in the reaction mixture. At longer times, compounds 5 through 9 disappear, and compounds 10 through 12 become the final hydrocarbon products. A large number of alcohols were also formed. Draw mechanisms explaining the formation of each of these products. Your mechanism should also account for the sequence of their formation. KWCH aC joa 7 1 3 inc men cH, xc-| HAC XS HC 6 ye HCH ~\CHy mc me. J we , we myc fis cu, M i Ke Ba me $ CHs HAC. We mC 10 u cH, 2 4, Draw mechanisms for the following reactions. SMLICI0, in ether HO. ©) on _DmButy, 11081 cus na (a) 9SiMey © cH, Hs 2 ° Sj, Bate hte (a) Fh 1h OH ; CRC OH144 (e) a) (g) (h) a i) o 3. Polar Reactions under Acidic Conditions but EQ. CR:CF; 2AM, on BRC i % Okt Loy cau onc’? ° HAG CH HC CHs _AICh, a Cs ne “10.4, oes 10, uo uo. COs {COsCHs Br Cw DNBS Su mse Am OCHS yy a OW on u ©. on ° ow 0 CHO eo ° + J ae ‘OH me che RY on yc. HO ascorbic acid The product, one example of an azo dye, was used for a long time as the coloring agent in margarine until it was discovered that it was carcinogenic. 1805 ‘When p-nitroaniline and salicylic acid are used as starting materials in the reaction in (j), Alizarin Yellow R, an azo compound used to dye wool. is obtained, What is the structure of Alizarin Yellow R? The following reaction helps explain why piperidine is a federally con- trolled substance,Problems 145 hen Ph NH + benzene N ‘at. H:SO, 1-{I-phenyleycloheryl)- piperidine, PCP (mn) oon wey 9 Che one (a) (p) The following reaction is the key step in the biosynthesis of cholesterol. ‘Compounds that inhibit the enzyme that catalyzes the reaction have been studied intensively recently because of their potential as anticholesterol drugs. squalene lanosterot oxide (q)_ The Wallach rearrangement. The following pieces of information should help you: (1) When 80-la- beled water is used as solvent, the product is labeled. (2) When one N in the starting material is selectively labeled with "5N, the label is found to be randomly distributed in the product. (3) The key intermediate is dica- tionic. (2) Think of the MesSi* group as a big proton.146 3. Polar Reactions under Acidic Conditions 4 A ‘OH y SN Me,SioTE yy \“ HN OsiMey 5 h - oe q O5iMey oc Ko MesSiHIN Yy MeSiOTT HO. Meo N. om — BL l \Phosaia (s) First draw a mechanism for formation of the five-membered ring. Then draw a mechanism by which the five-membered ring is converted into the six-membered ring simply by heating (no acid present), wi s oy Bry S, iH PhS AL Lh Br (t) The following two pieces of information should help you draw the mech- anism, (1) The rate-determining step involves cleavage of the CC! bond. (2) The rate decreases dramatically as the number of C atoms between N and Cl increases. (u) Me. Me 0, w)Problems 147 ow) ©. cous sac C0384 i + xycucog: Se. eC Me OH (%) SnCly is a Lewis acid ° o SnCl, CAL + mete SN co Pw 4 Pw : (y) Note the stereochemistry of the product! What does this tell you about the mechanism? ° ° Nano, nyho THCY ayn NH a ok BR, Re SiO Bs (2 (aa)