4H-Azepines

Physical Data Index 4H-Azepine-2-carboxylic acid... 

H-Azepine-2-thione, hexahydro-1 -methyl- C NMR, 7, 498 <79AJC567> 4H-Azepine-2,6,7-tricarboxylic acid, trimethyl ester AG 7, 499 (72JA2770)... 

H-Azepine, 2-(o-hydroxyphenyl)-synthesis, 7, 538 3 H-Azepine, methyl- H NMR, 7, 495 3H-Azepine, 3-methylring inversion barrier, 7, 14 3 H-Azepine, 2-methylene-isomerization, 7, 505 3H-Azepine, 7-(N-phthalimido) synthesis, 7, 538 4H-Azepine, 4,5-dihydro-cyclization, 7, 524... 

H-Azepine, 2,6,7-tri(methoxycarbonyl)-ring inversion, 7, 499 Azepine-1-carboxylic acid tricarbonylruthenium complexes, 7, 523 1 H-Azepine-2,3-dicarboxylic acid, 4,7-dihydro-6-phenyl-diethyl ester synthesis, 7, 539-540 1 H-Azepine-3,6-dicarboxylic acid... 

In some instances, with 1-methylcyclopropene as the 27t-component, isomeric mixtures of 4H-azepines, e. g. 39 and 40, are formed.84... 

Early work (B-69MI51600) on 7V-substituted-l//-azepines revealed that they undergo photoinduced ring contraction to bicyclic valence tautomers as indicated in Scheme 1. Subsequently, it has been found that 3H- and 4H- azepines enter into analogous ring contractions, as do some of their oxo and benzo derivatives. These transformations, which parallel those undergone by cycloheptatriene, are often thermally reversible and occur by an orbital symmetry-controlled disrotatory electrocyclic process. 

Azepines, prepared by base-promoted ring expansion of dihydropyridines, undergo a retro-reaction on treatment with HC1 or HBr (see Scheme 37 Section 5.16.4.2.3). In contrast, 4H-azepine (87) isomerizes in CHCl3-dilute hydrochloric acid or CHCI3-TFA to the 1//-azepine (71JCS(C)1237). 

H-Azepines are more rare than 1H- or 3H-azepines and only a few synthetic approaches have been developed. Of these the two main methods involve the ring expansion of six-membered heterocycles. Early studies revealed that highly substituted 4f/-azepines (269) result from the base-catalyzed ring expansion of 4-(chloromethyl)-l,4-dihydro-pyridines (267 Scheme 37). The reaction was found to be temperature and solvent sensitive, and azepines (268)-(270) have been isolated and characterized. However, later studies (68JCS(C)1675) on cyano derivatives (267 E = CN) show the reaction to be even more... 

N-Unsubstituted 1H-azepines are rare since, like the parent system, they tautomerize readily to the 3H-isomers in whose preparation they are often considered as transient intermediates (see Section 5.16.4.1.2(ii)). This rearrangement is particularly apparent with 2-amino- and 2-alkoxy derivatives since stabilization of the 3//-azepine is then possible by amidine and imidate type resonance. For the CH2-containing tautomers the order of stability appears to be 3H > 4H > 2H, a fact attested to by the facile thermal and base-catalyzed rearrangements of 4H- azepines to the 3H-tautomers (72CB982) and the rarity and inherent instability of 2//-azepines. The latter are well established as intermediates in the formation of 3H- azepines (74JOC3070) but have been characterized only as their benzologues. 

H-Azepines exhibit ring inversion activation energies of similar magnitude, e.g. 2,6,7-trimethoxycarbonyl-4H-azepine has a AG (at T c-40 5°C) of 46.8 2kJmol-1 (72JA2770). 

A few examples of the photoisomerization of 4H-azepines to l-azabicyclo[3.2.0]hepta-2,6-dienes have been noted, e.g. (49) -> (50) (80TL595). 

Base-catalyzed (NaOMe) isomerizations of 1H- and 4H-azepines to 3H-azepines are well known and most likely proceed via allylic anion intermediates (80TL595, 72CB982). 

Pyridine, 4-(chloromethyl)-l,4-dihydro-4H-azepines from, 7, 524 ring expansion, 7, 543-544 Pyridine, 2-chloro-6-trichloromethyl-as bactericide, 2, 514 Pyridine, 2-cyano-ions... 

Micotoxic 3H- and 4H-azepines, synthesis of 90JHC107. C-Substituted e-caprolactams, synthesis using desulfurization of thieno-annelated caprolactams 88MI17 90MI13. 

H-Azepine, 2-methoxy- H NMR, 7, 496 (77BCJ2013) IH-Azepine-l-carboxylic acid C NMR, 7, 498 (80AG(E)1016) IH-Azepine-l-carboxylic acid, methyl ester, tricarbonyliron complex X-ray, 7, 494 (70JCS(B)1783) 4H-Azepine-2-carboxylic acid, 6,7-diphenyl-, methyl ester... 

Four tautomeric forms, designated as 1H-, 2H-, 3H- and 4H-azepine may be drawn for azacycloheptatriene. IH-Azepine (1 R = H) is known as a very unstable (even at -78 "C in CDCI3 solution) red oil which in the presence of add or base rearranges to the marginally more stable colorless 3H-azepine (2 R = = H) (80AG(E)1016). 

Related to the aforementioned rearrangements are the ring expansions of l,2-dihydro-2-(p-tosyloxymethyl)pyridines in pyridine to 3H-azepines (71JOC978), and of the p-tosyloxy derivative (274) to the unstable 4H-azepine (275) by solvolysis in acetonitrile (73X391). 

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