Hofmann elimination rearrangement

Two efficient syntheses of strained cyclophanes indicate the synthetic potential of allyl or benzyl sulfide intermediates, in which the combined nucleophilicity and redox activity of the sulfur atom can be used. The dibenzylic sulfides from xylylene dihalides and -dithiols can be methylated with dimethoxycarbenium tetrafiuoroborate (H. Meerwein, 1960 R.F. Borch, 1968, 1969 from trimethyl orthoformate and BFj, 3 4). The sulfonium salts are deprotonated and rearrange to methyl sulfides (Stevens rearrangement). Repeated methylation and Hofmann elimination yields double bonds (R.H. Mitchell, 1974). 

The Somme let-Hauser rearrangement competes when Z is an aryl group (see 13-22). Hofmann elimination competes when one of the R groups contains a p hydrogen atom (17-6 and 17-7). 

Boekelheide and his collaborators [407] have described a two-step sequence for transforming sulfide linkages to carbon-carbon double bonds — Stevens rearrangement of sulfur ylides and Hofmann elimination — which they found particularly useful for the synthesis of cyclophane derivatives, such as the [2.2]metaparacyclophane-l,9-diene shown. The Ramberg-Backlund rearrangement (see Section 4.3.2) was unsatisfactory for such highly strained molecules. 

The Sommelet-Hauser rearrangement has rarely been used as a tool in organic synthesis and then only for very special systems [54], The reason is undoubtedly that the Hofmann elimination and the dealkylation reaction of quaternary nitrogen atoms are in direct competition with the ring expansion reactions of these substrates. 

Similarly, Bosch and co-workers(39) isolated from the potassium hydroxide-induced rearrangement of l,3,4-trimethyl-l-(3,4,5-trimethoxy-benzyl)-l,2,5,6-tetrahydropyridinium chloride, products corresponding to 73, 99, and by inference 101, together with a Hofmann-elimination product. An unambiguous method for preparing 2-benzyltetrahydropyridines from 2-bromopyridine, thus affording a wide selection of substituted benzomorphans has been published.(39a)... 

Treatment of l-ethoxycarbonylmethyl-l,2,5,6-tetrahydropyridinium bromides 86 with DBU in tetrahydrofuran at ambient temperature gave N-ylides 87, which under the reaction conditions applied isomerized to allenic compounds 88 and ring-opened products 89 (84CPB4600). Allenic compounds 88 were formed in a [2,3]-sigmatropic rearrangement, while ring-opened products 89 were obtained in a Hofmann elimination. 

The Hofmann amide rearrangement is a conversion of a primary carboxamides 230 into amines using aqueous NaOH and bromine (see review in Reference 330). This reaction is, in effect, an elimination of the carbonyl group from the amide and is therefore usually... 

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