Ring contraction pyridine rings

In quinoline and isoquinoline, the benzene ring is more receptive to fluorma-tion, its double bonds being saturated and the hydrogen atoms replaced in preference to those in the pyridine ring As with pyridine and its homologues, ring contraction takes place during fluorination with cesium tetrafluorocobaltate at... 

Azcpincs under acid conditions reportedly117-225 yield aniline derivatives although ring contraction to pyridines is more usual. Thus, highly substituted 3//-azepines, e.g. 28, with a vacant 7-position, formed by cycloaddition of 2//-azirines with cyclopentadienones, on heating in acetic acid isomerize rapidly to the correspondingly substituted anilines 29.117... 

The ring contraction of 3//-azepines is also promoted by acylating agents,54 35 and by arenesulfonyl halides.34 For example, in refluxing acetic anhydride A,-phenyl-3//-azepin-2-amine yields 2-acetamidodiphenylamine (22% mp 121-122°C),34 whereas A,A,-diethyl-3/7-azepin-2-amine (30) with 4-nitrobenzoyl chloride in pyridine yields the benzanilide 31.35... 

Azepines, although more stable than 1/f-azepines. readily undergo ring contraction to pyridine derivatives under acidic, basic, thermal, and photolytic conditions. 

The 1-benzoyl-l//-l,2-diazepines 3 undergo loss of the A -benzoyl group and ring contraction to provide the pyridines 4 in refluxing xylene (see Houben-Weyl, Vol. E7b, p 519).93... 

Ring contractions of pyran derivatives are occasionally valuable. The contraction of 3-halo-2-pyrones to 2-furoic acids under the influence of alkali has been studied and the conditions defined.58112113 The method is adaptable to the preparation of 3-furoic acid via furan-2,4-dicarboxylic acid58 and of 3,4,5-triphenylfuran-2-carboxylic acid.113 Another ring contraction involving halides is the conversion of 4-chloromethylpyrylium salts into furylmethyl ketones as indicated in Scheme 21.114 Pyridine oxides may be transformed with unexpected ease into furans through treatment with a thiol (Scheme 22).115... 

A kinetic study of thermolysis reactions of TV-crotyl substituted 1,2,4-triazoles was performed at temperatures in the range of 260-350 CC <00JHC1135>. Thermolysis of tetrazolo[l, 5- >]pyridazines, tetrazolo[l,5-a]pyrimidines and tetrazolo[l,5-a]pyridines allowed easy ring contraction to a facile preparation of cyanopyrazole heterocycles . 

Simoni et al. described <2000TL2699> that some fused tetrazoles readily participate in thermolytic ring contraction reactions which result in the formation of cyanopyrroles (Scheme 5). Thus, heating of tetrazolo[l,5- ]pyridine derivatives 14 at 150-170 °C yields the corresponding 2-cyanopyrrole 16. The process is believed to proceed via a nitrene intermediate 15. 

N, P, S, or C, is thermodynamically and kinetically favored, yielding pyridine, pyridinium, phosphaben-zene, thiopyrylium, or benzenoid rings. Ring-opening occurs with alkali cyanides ring contraction to... 

It is of some interest that the ring contractions giving rise to pyrimidine or pyridine derivatives may occur as simple thermal processes, for example (77TL2709 83LA1230). 

Huisgen found that 2-amino-3H-azepines are unstable under normal acylating conditions. Schotten-Baumann benzoylation, for example, brings about aromatization and, ultimately, formation of 2-(benzamido)diphenylamine, whereas p-nitrobenzoyl chloride in cold pyridine yields 2-(p-nitrophenyl)-l-phenylbenzimidazole. Benzenesulfonylation, however, proceeds normally at the exocyclic nitrogen. The mechanistic rationale for these ring contractions is outlined in Scheme 8 (b-69MI516oo). 

Most important is the conversion of 4//-pyrans to pyridines. Ring contraction and ring expansion reactions of 2//-pyrans and 2//-thiopyrans also occur. 

In contrast, 3-tert-butyI-6-chIoropyrido[2,3-6]pyrazine rapidly reacts with KNHj-NHj to yield a ring contraction product, 2-tm-butyl-l//-imidazo[4,5-6]pyridine (Scheme 4). The transformation is reminiscent of the ring contraction undergone by 2-methylthio-4,6,7-triphenyIpteridine to yield 6,8-diphenyI-2-methyIthiopurine.120 Although no ff-adduct could... 

Another possibility is that these compounds were unsaturated aldehydes that resulted from ring contraction during deamination followed by elimination, during acetylation at 100° in pyridine. 

Vinylpyrazolo[4,3-h]pyridine (194) has been prepared in good yield by photochemical ring contraction of pyridodiazepine 193 in dichloromethane or methanol. The yield was improved by thermolysis of 193 in refluxing xylene97 (cf. Section II,A,9,a). 

All four pyrrolo[2,3]pyridines can be prepared by photochemical ring contraction of naphthyridine derivatives, e.g. (210). Although reliable, multistep syntheses are needed for the photolysis substrates, which can only be irradiated in small quantities (Scheme 67) <58LA(612)153>. 

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