Side-Chain Isomerization

Side-Chain Isomerization. Arylalkanes undergo acid-catalyzed isomerization in the side chain in a way similar to the skeletal rearrangement of alkanes.70-72 There are, however, notable differences. Propylbenzene, for instance, yields only a small amount (a few percentages) of isopropylbenzene 73 Similarly, sec-butyl- and iso-butylbenzene are interconverted at 100°C with wet A1C13, but only a negligible amount of tert-butylbenzene is formed.74 In the transformation of labeled propylbenzene the recovered starting material was shown to have equal amounts of labeling in the a and p positions of the side chain, but none in the y position 73 

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Selten-gummi, n. side wall (of a rubber tire), -isomerie, /. chain isomerism, -kante, /. lateral edge, -kette, /. side chain, -ketten-isomerie, /. side-chain isomerism, -kraft, /. component force, component, -lage,/. lateral position, -l ge, /. length of a side, lateral length, -riss, m. side elevation. -lohr, n., -rohre,/. side tube, branch tube, branch pipe, seitens, adv. on behalf (of), on the part (of), seltenstandlg, a. lateral. 

K Zhang, F Lepage, G Cuvier, J Astoin, MS Rashed, TA Baillie. The metabolic fate of stiripentol in the rat. Studies on cytochrome P-450-mediated methylenedioxy ring cleavage and side chain isomerism. Drug Metab Dispos 18 794, 1990. 

Since the transformation of isopropylbenzene to propylbenzene is not effected in the absence of benzene, it is obvious that this side-chain isomerization proceeds via intermolecular alkyl transfer. The transfer occurs below 530 K at LHSV of 11.4, the 50% conversion level is reached at 560 K. 

What happens when isomerization is performed is that the double bond of the allylbenzene safrole migrates to the more energetically favorable position between the alpha and beta carbons of the propyl side chain. Thus isosafrole, a propenylbenzene, is born. 

An E-Z discrimination between isomeric oxaziridines (27) was made by NMR data (69JCS(C)2650). The methyl groups of the isopropyl side chains in the compounds (27) are nonequivalent due to the neighboring carbon and nitrogen centres of asymmetry and possibly due to restricted rotation around the exocyclic C—N bond in the case of the Z isomer. The chemical shift of a methyl group in (Z)-(27) appears at extraordinarily high field, an effect probably due to the anisotropic effect of the p-nitrophenyl group in the isomer believed to be Z. 

Early efforts to partially synthesize 20-keto and 17a-hydroxy-20-keto steroids led to ring D-expanded products isomeric with the desired compounds. Darzens condensation of 3/5-hydroxyandrost-5-en-17-one acetate (75) with ethyl a,a-dichloropropionate, followed by alkali treatment and decarboxylation, gives both the expected 3j5-hydroxypregn-5-en-20-one (78) and an isomer now known to be 17a-methyl-D-homo-17-ketone (79).36,37a alternative route for the introduction of the two carbon side chain, Ruzicka... 

It has been shown that acetamidothiophenes 22 can be converted to either chlorothieno[2,3-h]pyridines 23 or chlorothieno[2,3-h]pyridinecarboxaldehydes 24 using POCI3 and DMF by appropriate choice of reaction conditions. However, unlike the acetanilides, initial ring formylation rather than side-chain formylation is believed to lead to the formation of the pyridine ring. These reactions have been extended to the synthesis of the isomeric thieno[3,2-I>]- and thieno[3,4-I>]pyridines, 25 and 26, from 3-acetamidothiophene and 3-acetamido-2,5-dimethylthiophene, respectively. 

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