6.7- Dihydro-l//-azepines

Reports of pericyclic cyloadditions to other azepine systems are rare. Addition to the diene system of 6,7-dihydro-l//-azepines occurs readily with DMAD (72CPB1740) and with N-phenylmaleimide (73JA7320). The 5,5a-dihydro-3-benzazepin-2-one (157), a suspected but non-isolable intermediate in the formation of l,2,4,5-tetrahydro-3//-3-benzazepine-2,4-diones by photoaddition of diphenylketen to amino-2//-azirines, has been trapped in the photolysate by N-phenyl-1,3,4-triazoline-2,4-dione as the [4+2]tt adduct (158). Its structure was confirmed by X-ray analysis (80JOC2951). 

A two-carbon ring expansion reaction of 5-membered cyclic enamines gave 6,7-dihydro-l//-azepines on reaction with dimethyl acetylenedicarboxylate <06ZN(B)385>. 

Indene derivatives (70JOC1155 88TL2769) with TADs also form [2 + 2] adducts, e.g., 219. Interestingly, some 6,7-dihydro-l//-azepines, e.g., 220, which are formally able to form both Diels-Alder and ene-type adducts, when treated with TADs provided only [2 + 2] adducts 221 (86CB2114). 

The [ 2S+ 4S] electrocyclic rearrangement of the deuterated anrz-2-azatricycloheptane (66) at 350 °C yields l-methoxycarbonyl-6,7-dihydro-If/- azepine in which the deuterium is statistically distributed between the C-2, C-3, C-6 and C-7 positions. Presumably at 350 °C rapid 1,5-H(D) shifts are taking place involving the thermodynamically less stable 2,7-dihydro-lf/-azepine (67) (73JA7320). 

Dihydro-l//-azepines have been prepared by the reaction of (Z,Z)-1,6-dibromohexa-2,4-dienes with primary amines <94JCS(CQ67>, and the reaction of 3-iminoprop-1 -enylamines with pentacarbonyl( 1 -methoxyprop-2-... 

IH-Azepine, 1-methoxy carbonyl-cycloaddition reactions, 7, 522 with nitrosobenzene, 7, 520 tricarbonyliron complex acylation, 7, 512-513 conformation, 7, 494 tricarbonylruthenium complex cycloaddition reactions, 7, 520 1 H-Azepine, l-methoxycarbonyl-6,7-dihydro-synthesis, 7, 507... 

Pyrolysis of dimethyl 4-methoxy-2,5,7-trimethyl-4,5-dihydro-l//-azepine-3,6-dicarboxylate (6a), or the corresponding 4-succinimido derivative 6b, at 160-180°C in a sublimation tube containing glass beads furnishes the 4//-azepine 7.121... 

Curiously, 6-(chloromethyl)-4-methyl-2-methylene-3-phenyl-3-azabicyclo[4.1.0]hept-4-ene-l,5-dicarbonitrile (31), obtained from 4,4-bis(chloromethyl)-2,6-dimethyl-l-phenyl-1,4-dihydro-pyridine-3,5-dicarbonitrile, rearranges via 4-(chloromethyl)-7-methyl-2-methylene-l-phenyl-2, 5-dihydro-l//-azepine-3,6-dicarbonitrile (32) to yield the 4-(chloromethylene)-4,5-dihydro-1//-azepine 33 as the final product.127... 

Ethyl 6,7-diaryl-3-hydroxy-2-oxo-2,5-dihydro-l//-azepine-4-carboxylates, e.g. 20, with diazomethane methylate solely at the 3-hydroxy group, whereas with Meerwein s reagent the 7-ethoxy-4/7-azepines, e.g. 21, are formed.48... 

With cyanide ion in aqueous ethanol azepinedicarboxylate 3 forms the corresponding racemic 4,5-dihydro-l//-azepine-4-carbonitrile (85%),121,241 whereas with dimethyl 2,5,7-trimethyl-4//-azepinc-3,6-dicarboxylate (6) diastereospecific addition occurs to give racemic lrans-5-me thy 1-4.5-di hydro-1-//-azepine-4-carbonitrile 7 together with a small amount of the trans 4S-methoxy-5 / -methyl compound 8.121... 

A mixture of 6-mesyl-6,7-dihydro-5/f-dibenz[ ,c]azepine (29, R = Ms 13.67 g, 50 mmol) in anhyd DMSO (160 mL) and t-BuOK (18.7 g, 165 mmol) was stirred for 45 min at 20 C under N2. Another portion of /-BuOK (2.65 g, 25 mmol) was added and stirring was continued for a further 45 min. The mixture was transferred to a separating funnel with ice-cold H20 (1.1 L) and extracted with Et20 (700 mL). The aqueous phase was extracted again with Et,0 (200 mL) and the combined ethereal extracts were then dried for 2 h (CaCl2) and evaporated to give the crude product as a pale-yellow oil (9.61 g, 99 %). which was purified bv distillation (bp 125 126/0.01 Torr) to give the product as colorless crystals yield 8.25 g (85 %) mp 84-85 C. 

A diastereoselective imine alkylation and a palladium-catalysed biaryl coupling were important steps in the diastereoselective synthesis of 6,7-dihydro-5//-dibenz[c,e]azepines (Scheme 7) starting from (R)-l-(2-methoxyphenyl)ethylamine. Selection for the... 

There are only a few reports concerning the peracid oxidation of azepines. 30% Hydrogen peroxide oxidizes TV-alkyl-6,7-dihydro-5iT-dibenz[c,e]azepines to their TV-oxides (75ZN(B)926), whereas MCPBA has been used to prepare the 3H-2-benzazepine TV-oxide (88) (74JOC2031). TV-Oxidation of 2,3,4,5-tetrahydro-lH-l-benzazepine with MCPBA is accompanied by dehydrogenation to the 4,5-dihydro TV-oxide (89) (79JOC4213). 

Alkylation of 3-methyl-l,2,4,5-tetrahydro-3H-3-benzazepin-2-one in THF-DMF solution containing sodium hydride, with primary and secondary alkyl halides and with a-bromoesters, results predominantly in 1-monoalkyl derivatives, whereas with dibromoalkanes, 1,1-spiro derivatives are formed <80T1017). Apparently, 6,7-dihydro-5//-dibenz[6,condense with benzaldehyde or with nitrosobenzene at the active methylene group (55JA3393). 

In a substrate-dependent, palladium-catalyzed domino N-benzylation/ intramolecular direct arylation process, tosylamides 133 and 2-bromobenzyl bromides 134 reacted to form dibenzo-l,2-thiazepine dioxides 135 exclusively, or gave mixtures that also contained 6,7-dihydro-5H-dibenzo[c,e] azepines 136 (14JOC10899). 

Cl5H13NO, 6,7-Dihydro-6-methyl-5H-dibenz[c,e]azepin-5-one, 39B, 211 Cl 5H1 i,Ni,02 f 4,5-Benzo-8,11,11 - trimethyl-1, 2,7,1 0-tetraazatricyclo-[7.3,0.0 ]dodeca-2,9-diene-6,12-dione, 46B, 273 Cl5H1sBr2N, 1,1-Bis(bromoethyl)-l,2,3,4-tetrahydroacridine, 46B, 273 Cl5H15N2O5, Methyl 8-methoxycarbonylmethyl-2-oxo-2,3,3a,8-tetrahyd-ro-1H-pyrazolo[5,1-a]isoindol-3-carboxylate, 41B, 346 Cl5H16N2O2, 5,7-Dihydroxy-6,6-dimethyl 6,7-dihydrodibenzo[d,f](1,3)-diazepine, 44B, 256... 

H-Dibenz[6/]azepine, 10,1 l-dihydro-5-niethyl- C NMR, 7, 498 <74JCS(P2)1648) 5H-Dibenz[r c]azepine H NMR, 7, 497 <81LA240) 6H-Dibenz[c,e]azepine, 6-allyl-5,7-dihydro- CNMR, 7, 498 <79JPS890) 5H-Dibenz[6,/]azepine-5-carboxylic acid, 10,11-dihydro-, ethyl ester C NMR, 7, 498 <74JCS(P2)1648)... 

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

Dimethyl 4-ethoxy-2,7-dimethyl-4,5-dihydro-l 7/-azepine-3,6-dicarboxylate (1) with sodium ethoxide in refluxing diethyl ether, or on standing at room temperature in carbon tetrachloride solution, readily loses ethanol to yield dimethyl 2,7-dimethyl-4//-azepine-3,6-dicar-boxylate (2).29 The 4-methoxy derivative is also unstable and on warming at 100 C under reduced pressure loses methanol to yield the same product (44%).120... 

A diatropic cation 15 is also noted in strong acid solution for 7//-pyrrolo[l,2-a]azepin-7-one (14), prepared by dehydrogenation of its 5,6-dihydro derivative 13.217 It is presumed that the deep-red solution produced on treating 7-methylene-7//-pyrrolo[l,2- azepine (16), prepared from the ketone 13 as indicated, with strong acid is indicative of the formation of 7-methylpyrrolo[l,2-a]azepinium cation 17 however, the salt could not be isolated nor a satisfactory HNMR spectrum obtained.217... 

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