The ordering is allyl chloride 1-chloropropane 2-chloropropane. Iodide is a good nucleophile but a weak base, and polar aprotic solvent acetone favours its SN2 reaction. SN2 reaction and C–Cl cleavage occur in one step; precipitation of sodium chloride can also favour halide exchange without changing the basic steric comparison.
The primary saturated chloride supplies the reference rate. Allyl chloride is also primary, but its neighbouring pi system stabilizes the developing delocalized electronic structure in the substitution transition state. It can therefore react about 64 times faster without requiring a free allylic carbocation. The secondary chloride is sterically crowded at the attacked carbon, making backside approach and the crowded transition state less favourable; its rate is about 0.02 times the primary value. The leaving group and nucleophile are the same in the comparison, so assigning the ordering to different halide leaving groups would be incorrect. If prefactor differences are neglected, at 333 K gives roughly and for the allylic and secondary substrates respectively: modest barrier changes produce large rate ratios.
The first product is , with the original alkene geometry retained. methoxide attacks the primary saturated carbon bearing bromine from the backside. Its oxygen lone pair forms the new C–O bond as the C–Br bonding pair leaves with bromide. The other bromine is vinylic, directly bonded to an sp carbon: ordinary SN2 reaction is unfavourable there, and ionization would require an unstable vinyl cation. Thus the primary alkyl bromide is replaced selectively, rather than replacing the vinylic halide or moving the double bond. There is no observable inversion label at the attacked carbon because it is a methylene.
The second product is sodium 4-propoxybutane-1-sulfonate, . sodium hydride first removes the alcohol proton, giving propoxide and hydrogen. The propoxide oxygen then attacks the primary ring carbon bonded to the ring oxygen; simultaneous cleavage of that carbon–oxygen bond opens the sultone. The departing ring oxygen remains attached to sulfur as part of the resonance-stabilized sulfonate anion. The carbon attached directly to sulfur is not the substitution site, because cleavage there would not expel the same stable sulfonate leaving group. This is carbon-centred ring opening of a cyclic sulfonate ester, not addition across an S=O bond.
Original electron-pair arrows for selective primary-carbon substitution and propoxide opening of the four-carbon sultone
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Aqueous base selectively converts the methyl ester to a carboxylate, and brief acidification gives the corresponding monoacid while retaining the tert-Butyl ester. At the methyl-ester end, a hydroxide lone pair attacks the acyl carbon and the carbonyl pi pair moves to oxygen. The tetrahedral intermediate collapses as the oxygen anion reforms C=O and the acyl C–OMe bond breaks to methoxide. proton transfer then gives the carboxylate and methanol. carboxylate formation makes the net saponification effectively irreversible under the basic conditions; protonation protonates that carboxylate.
The tert-Butyl ester reacts more slowly under these conditions because its bulky alkoxy group hinders acyl attack, and tert-butoxide is a stronger base and poorer leaving group than methoxide. The selectivity is kinetic, not an assertion that tert-butyl esters can never undergo base hydrolysis. The work-up should be sufficiently mild and brief to avoid the separate acid-labile pathway.
Anhydrous trifluoroacetic acid instead removes the tert-butyl group, leaving the methyl ester. protonation activates the ester; in a useful reactive protonation form the alkoxy oxygen bears the proton. The O–C(tert-butyl) bond then cleaves with its electron pair going to oxygen, producing the carboxylic acid and a tert-butyl-cation-like fragment. Loss of a methyl proton gives 2-methylpropene and regenerates the acid catalyst. Carbonyl-oxygen protonation and charge delocalization can precede cleavage; drawing alkoxy-oxygen protonation is a transparent way of tracking the bonds broken. The key distinction is alkyl–oxygen cleavage here versus acyl–oxygen cleavage in the base reaction. Methyl-cation formation is strongly unfavourable, and without water ordinary acid-catalysed methyl-ester hydrolysis is not available. No water is required to account for the tert-butyl deprotection or its alkene by-product.
Original mechanisms contrasting tetrahedral acyl substitution with acid-promoted tert-butyl alkyl–oxygen cleavage
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Build the phenethyl grignard reagent, use one portion to make a phenethyl-substituted ester, and add two further equivalents to that ester. Write ; the target is , so all three carbon substituents must be phenethyl, not benzyl.
hydroboration followed by oxidation of styrene gives : use in a suitable ether, followed by alkaline hydrogen peroxide. The Anti-Markovnikov addition regiochemistry is essential; acid-catalysed Markovnikov addition of water would give the wrong alcohol. Convert the primary alcohol to with phosphorus tribromide, then form with magnesium in dry ether. The organomagnesium reagent must be prepared and used without a protic solvent.
carboxylate one portion with carbon dioxide and acidify to obtain , then esterify with ethanol under acid catalysis to give . Treat the isolated ester with at least two equivalents of another portion of and then perform an aqueous acidic work-up:The first addition to the ester gives a ketone after ethoxide elimination; the second addition gives the tertiary alkoxide. Work-up supplies its OH proton. The extra central carbon comes from carbon dioxide, and each original styrene contributes one intact eight-carbon phenethyl unit. The resulting carbon count is , matching the target skeleton.
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