2-Azabicyclo hepta-2,6-dienes

The facile, photoinduced valence isomerization of ethyl 1//-azepine-l-carboxylate to ethyl 2-azabicyclo[3.2.0]hepta-3,6-diene-2-carboxylatehas been studied as a potential solar energy storage system.101102 Unfortunately, the system proved to be inefficient due to build up of polymeric material during the thermally induced, exothermic retro-reaction. 

Azabicyclo[3.2.0]hepta-3,6-dienes are the 4 5 bicyclic valence isomers of 1//-azepines. In some cases there is an equilibrium between the bicycle and the azepine, whereas with other 1//-azepines photolysis yields an azabicycloheptadiene that can be isolated and characterized. For example, ethyl 2-azabicyclo[3.2.0]hepta-3,6-diene-2-carboxylate (1), the photoinduced valence isomer of ethyl l//-azepine-l-carboxylate (2), undergoes a clean, exothermic, first order, electrocyclic ring opening (AG = 20 kJ mol-1) to the parent 1//-azepine 2 on heating at 113-143C in an inert solvent (e.g., hexadecane).101... 

In contrast, thermolysis of the N-unsubstituted 4,6-di-fert-butyl-2-azabicyclo[3.2.0]hepta-2,6-diene (3) yields 3,6-di-ter -butyl-3//-azepine (4).70t287,288... 

Flash-vacuum pyrolysis of 3-alkyl-or 3-aryl-2-azabicyclo[3.2.0]hepta-2,6-dienes 5a-c, prepared by the action of a Grignard reagent (RMgX) on the 3-methoxy derivative 5 (R = OMe), furnishes mixtures of the 2- and 7-substituted 3//-azepines 6 and 7, respectively.113... 

Azabicyclo[4.1.0]hept-3-enes, e. g. 13, are available from 1,4-dihydrobenzenes 12 by the route indicated, and are useful precursors for the synthesis of specifically substituted 1//-azepines free from isomeric contamination.61 For example, low temperature addition of bromine to bicycle 13 yields the dibromo derivative 14 which, with powdered sodium methoxide in tet-rahydrofuran, undergoes a double dehydrobromination followed by electrocyclic ring opening of the resulting 7-azabicyclo[4.1.0]hepta-2,4-diene 15 to give methyl l//-azepine-l-carboxylate (16). 

A solution of dimethyl 3-acetyl-3-azatetracyclo[3.2.0.02-7.04 6]heptane-l,5-dicarboxylate (2, R1 = Ac R = H), formed by the photolysis (14 h 125-W Hg lamp under N2) of dimethyl 7-acetyl-7-azabicyclo-[2.2.1]hepta-2,5-diene-2,3-dicarboxylate (1 R1 = Ac, R2 = H 1 g, 4mmol) in Et20 (400 mL) at — 40 C, was evaporated to dryness under reduced pressure. The residue (0.7 g, 2.8 mmol) was dissolved in CHC1, and the solution heated under reflux for 1 h. Evaporation of the solvent yielded the crude product which was purified by column chromatography (silica gel, C,H2C12). The yellow fractions were collected and, after removal of the solvent, the residual oil was distilled in a sublimation apparatus to give 3 (R1 = Ac R2 = H) as a yellow oil yield 0.8 g (80%) bp 50 60 C/5 x 10 4 Torr. 

The intermolecular process is employed almost exclusively for the preparation of 1H-azepines and in most cases involves addition of a singlet nitrene133 to the arene to give, initially, an unstable 7-azabicyclo[4.1.0]hepta-2,4-diene (benzaziridine) intermediate, e. g. 1, which undergoes an electrocyclic ring opening to the l//-azepine, e. g. 2. 

A unique isomerization has been observed on heating 5-acctyl-2-(cycloalkylamino)-3//-azepines, e.g. 24, in solution in their respective amines at 170 C.119 Rearrangement, via a 3-azabicyclo[4.1.0]hepta-2,4-diene intermediate, affords the 6-acetyI-3//-azepine, e. g. 26. The process appears to be base-catalyzed as there is no reaction in xylene at 170 C. 

Theoretically, valence isomerization of 3//-azepincs can give rise to 2-azabicyclo[3.2.0]hepta-2,6-dienes 20 and/or the isomeric fused azetines, 6-azabicycIo[3.2.0]hepta-2,6-dienes 21. Practically, however, 2-alkoxy- and 2-amino-3//-azepincs 19, on photolysis, yield the 2-azabicyclic systems 20 exclusively, since such structures are stabilized by imidate or amidine resonance.238... 

Attempts to methylate the carbanion derived from ethyl 2-(diethylamino)-5-phenyl-3//-azepine-3-carboxylate (14) with iodomethane leads to the formation of the 3-azabicyclo[4.1.0]cyclo-hepta-2.4-diene 15.225... 

Irradiation of 3-benzoyl-2-methoxy-3//-azepine (32) in methanol gives rise to a mixture of the 3-azabicyclo[4.1.0]hepta-2,4-diene 33 (detected by HNMR spectroscopy, but not isolated), 2-methoxy-3-phenacylpyridine(34), and a trace of 2-phenylfuro[2,3-A]pyridine (35), this last product being an artefact derived from the phenacylpyridine 34.246... 

Acyl-3.4-benzo-2-azabicyclo[3.2.0]hepta-3,6-dienes 1, on heating at 250-280 C for a short time without solvent, rearrange to the 1-acyl-1-benzazepines 2 (Method A).23-38 In some cases, rearrangement is accompanied by minor amounts of Ar-aeyl-l-naphthylamine and, at higher temperatures, the acylnaphthylatnine can become the major product (see Section 3.2.2.6.). In the presence of silver(I) tetrafluoroborate (Method B) rearrangement takes place at lower temperatures but the yields of benzazepine are inferior as the silver(I) ion also catalyzes the reverse reaction (see Section 3.2.2.1.). 

Benzoyl-l-methyl-3,4-benzo-2-azabicyclo[3.2.0]hepta-3.6-diene (3) at 250"C yields exclusively l-benzoyl-2-mcthyl-l//-l-benzazepine (4).23 In contrast, silvcr(I) ion catalyzed ring expansion of 3 yields a mixture of the rearranged bicycle 5 (43 %), starting material (43 %), and the isomeric 1 H-l-benzazepines 4 (8%) and 6 (4%).23... 

The structure of the product obtained by the silver(I) ion catalyzed ring expansion of anti-1-chloro-2,3-benzo-7-azabicyclo[2.2.l]hepta-2,5-diene, formulated tentatively as 1-methoxy-l/f-1-benzazepine,140 has been shown to be 2-methoxy-6,7-benzo-l-azabicyclo[3.2.0]hept-3-ene... 

The thermal addition of dimethyl acetylenedicarboxylate to indoles, unlike the photocycloaddition (see Section 3.2.1.4.1.1.), proceeds via a polar stepwise process to yield, initially, 3,4-benzo-2-azabicyclo[3.2.0]hepta-3,6-dienes which in some cases are isolable,13 141 but which, in general, ring open in situ to give the indolylacrylates 3 and/or undergo electrocyclic ring expansion to 1-benzazepines.21... 

The thermally induced electrocyclic ring opening of 2-alkyl- and 2-acyl-3.4-benzo-2-azabicyclo-[3.2.0]hepta-3,6-dienes 2 to l//-l-benzazepines 1 (see Section 3.2.1.4.1.1.) are photorever-sible.23,37 38 Also, l-acyl-1//-benzazepines 1 (R = acyl), in refluxing xylene in the presence of silver(I) tetrafluoroborate, are in thermal equilibrium with their valence isomers the 2-acyl-3,4-benzo-2-azabicyclo[3.2.Oj nepia-3,6-uienes 2 (R = acyl).23-38... 

Another photochemical ring enlargement leading to a 1,3-oxazepine is the formation of 2-phenyl-l,3-oxazepine (13) by irradiation of 4-phenyl-2-oxa-3-azabicyclo[3.2.0]hepta-3,6-diene (11).12 It is proposed that the process involves the azirine 12 as an intermediate. 

Phenyl-2-oxa-3-azabicyclo[3.2.0]hepta-3,6-diene (11 0.200 g, 1.17 mmol) in hexane was irradiated in a quartz vessel using a Rayonet photoreactor to give the product as a yellow oil yield 0.160 g (SO %). The compound can be distilled below 100 C at 10 4Torr. It gradually resinifies when kept in air at 20 C. 

Azabicyclo[2.2.i]hepta-2,5-dienes, Naphthalen-1,4-imines, and Anthracen-9,io-imines... 

Recently, a new reactivity index has been proposed (80H(14)1717> which predicts accurately the site selectivity of photocyclization of substituted cycloheptatrienes to their bicyclic valence tautomers. Unfortunately, application of the method to substituted lH-azepines is far less successful. For example, for 2-methyl-l-methoxycarbonyl-lH-azepine (37 R = 2-Me) AGrs values for C-2—C-5 and C-4—C-7 cyclization are calculated as 0.093 and 0.040 kJ mol-1, respectively, i.e. predicting the 1-methyl isomer (39) as the major product. Experimentally, however, the reverse is true, the yields being 93.5% for 3-methyl (38 R = Me) and 6.5% for 1-methyl (39 R = Me). The corresponding photoinduced valence isomerizations of 1-benzazepines to 3,4-benz-2-azabicyclo[3.2.0]hepta-3,6-dienes (38a) have been recorded (80JOC462). These isomerizations have also been achieved thermally in the presence of silver ion (80TL3403). 

Ring contractions of 3H-azepines analogous to those outlined in Scheme 1 can give rise to either a 2-azabicyclo[3.2.0]hepta-2,6-diene (40) or the fused azetine (41). Odum and Schmall found exclusive formation of the 2-azabicycloheptadienes (40) for the 3H- azepines (2 R1 = H, R2 = OEt, NH2 or NMe2), and argued that the alternative pathway to the bicyclic azetines (41) would involve loss of amidine or imidate resonance in the product (69CC1299). 

Valence tautomerization to the bicyclic azetine (47 R1 = OEt, R2 = Me) has been observed in the photosensitized (PlfcCO or PhCOMe) ring contraction of the otherwise photostable 2-ethoxy-4,5-dihydro-3.H-azepine (46 R4 = OEt, R2 = Me) (71JOC1934). In contrast, sensitized photolysis of the dimethylamino derivative (46 R1 = NMe2, R2 = H) gave only polymers. Unsensitized photolysis in pyrex yields several cyclic products, all of which are attributable to the intermediacy of an unstable 7-azabicyclo[3.2.0]hepta-3,6-diene (47 R1 = NMe2, R2 = H) (73CC327). 

Anomalous isomerizations have been noted during the photolytic and thermal rearrangements of 3-acyl-2-methoxy-3//-azepines (2 R -acyl, R2 = OMe) and 3-acyl-3H- azepin-2-ones (69T5217). Irradiation in methanol solution produces mixtures of 3-azabicyclo[4.1.0]hepta-2,4-dienes (28 R1==acyl and H, R2 = OMe, R3 = H) (or -4-ene-2-ones) and 3-phenacylpyridines (or pyridones), albeit in poor yields. Detailed, but tentative, arguments involving azanorcaradiene and/or diradical intermediates are presented to explain the formation of these unusual products. 

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

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