Dibenzo 6/ azepines

Both acridone and dibenzo[6,/]azepine produce unexpected products (Scheme 7.39) when reacted with dimethylvinylidene carbene (7.1.18.A). Acridone reacts initially at the nitrogen atom to produce the 10-(3,3-dimethylallenyl) derivative (13%) and a pyrroloacridone (10%) which, if the structure is correct, could be derived from the allene by sigmatropic shifts [16]. The dibenzoazepine reacts as expected to produce a cyclopropyl derivative but, under the reaction conditions, the adduct rearranges spontaneously to yield a 1,6-methanodibenzo[b,/]cyclo-prop [J]azepine, the structure of which was confirmed by X-ray crystallography [17]. 

In tests for autonomic activity and for reserpine antagonism, several of the compounds described in this section showed activity comparable to that of the drug imipramine (a dibenzo(6,/)azepine).287... 

J. Schmutz, Neuroleptic piperazinyl-dibenzo-azepines. Arzneim.-Forsch. (Drug Res.), 25 (1975)712-719. 

Methyl-dibenzo[b,fl azepine (4.1 g), N-diethylaminoborane (1.7 g) and freshly distilled toluene (150 cc) are introduced into a 500 cc three-neck flask equipped with a dropping funnel and a condenser, and protected against moisture by a calcium chloride guard tube. The solution Is heated under reflux (110°C) for 22 hours under a nitrogen atmosphere and then cooled. A 2N aqueous sodium hydroxide solution (33 cc) is then run in followed by an... 

N aqueous methylchloramine solution (190 cc), the addition of which takes 9 minutes. The mixture is stirred for 1 hour and then decanted. The organic layer is washed with water until it has a pH of 6 and is then extracted with 2 N hydrochloric acid (5 times 50 cc), dried over sodium sulfate, filtered and evaporated. Recrystallization of the residue from petroleum ether yields some unconverted 5-methyl-dibenzo[b,f] azepine (2.17 g). 

The aqueous acid solution is rendered alkaline by adding 2 N sodium hydroxide solution. After extracting with diethyl ether (3 times 100 cc), drying the extracts over potassium carbonate, treating them with decolorizing charcoal, filtering and evaporating the ether, a yellowish oil (0.9 g), identified as 5-methyl-10-methylamino-10,11 -dihydro-dibenzo[b,f] azepine, is obtained in a yield of 37.5%. 

Chemical Name 5-(3-Quinuclidinyl)-10,11 -dihydro-dibenzo [b,f] azepine Common Name —... 

By analogy with the formation of3//-azepines by cycloaddition of 2//-azirines withcyclopenta-dienones, l,3-diphenyl-2//-inden-2-one (58) and its dibenzo analog 60 enter into [4 + 2] cycloadditions with 27/-azirines to give 3//-2-benzazepines 59 and phenanthro[9,10-e]azepincs 61, respectively.96... 

F-Dibenz[/),/]azepines enter into 1,3-dipolar cycloadditions with diarylnitrilimines 14, generated in situ from hydrazonyl chlorides, to give dibenzo[7>,/]pyrazolo[3,4-rf]azepines, e.g. 15, in good yields.233... 

Bis(2-nitrophenyl)amine (la) is reduced by zinc/ sodium hydroxide to a mixture of 117/-dibenzo[r, /][l,2,5 triazcpine (2a) and the V-oxidc 3a.325 The reaction of Ar-methylbis(2-ni-trophenyl)amine with lithium aluminum hydride provides 11-methyl-1 l//-dibenzo[c,/][l,2,5]tri-azepine (2b).153... 

Stereochemistry also plays an important role in the recently disclosed 3,4-dihydropyrimidinethione analogs [32]. Racemic dihydropyrimidine derivative (32) is reported to inhibit activation by the TRPA1 agonist HH-dibenzo[fc,e]azepine-10-carboxylic acid methyl ester (16) with an IC50 value of 128 nM for human TRPA1 in HEK293 cells. 

Brown s result was supported by later experiments in which bromonium ions were generated by bubbling gaseous hydrobromic acid through a solution of bromohydrins in halogenated solvents. Under these conditions, bromine is eliminated as it is formed, so that the resulting alkene is observed directly (Scheme 15). This method has been applied to the bromohydrins derived from cis- and trans-stilbenes (Scheme 16) and from 5//-dibenzo[a,d]-cycloheptene and -azepine systems ([29a] and [29b] respectively Scheme 17), in which steric constraints should favour elimination (path a) as against substitution (path b). 

Aminomorphanthridine was reacted with EMME in 1,2,4-trichlorobenzene under nitrogen at 100°C for 1 hr, then at reflux temperature for 3 hr, to give 53% of dibenzo[c/]pyrimido[l,2-n]azepin-4-one (1159) and 1% of dibenzo[c/]pyrimido[ 1,2-n]azepin-2-one (1160) (80JHC341). 

Dipolar cycloaddition is another route to benzopyrrolo[l,2-a]azepines by pyrrole ring formation. The azomethine ylide derived from imine 88 and difluorocarbene adds to DMAD to produce dimethyl 3-fluoro-9H-dibenzo[c,/]-pyrrolo[l,2-fl]azepine-l,2-dicarboxylate 89 in 20% yield (Equation (12)... 

This review is based on Mosby s book cited above and covers the literature through 2009 together with several articles published in 2010. It includes pyrido[l,2-fl]azepines and their hydro products as well as linearly or angularly fused benzo and dibenzo derivatives. Patents are taken into account provided they reveal important aspects of synthesis or application. 

Bei der photolytisch ausgelosten Umlagerung von 5-Nitroso-10,11-dihydro-5H-(diben-zo[b f]azepin) in Benzol bei 5-10° unter Sauerstoff entstehen 2-Nitro-10,l 1-dihydro-[Schmp. 179-181° (Diethylether)] bzw. 4-Nitro-10,11 -dihydro-5H-(dibenzo[h f]azepiri) [Schmp. 64-65° (Ethanol)] in 28 bzw. 21%iger Ausbeute3 ... 

Chemical shifts for the azepine ring protons, as might be anticipated from their non-planar, polyene character, lie in the vinyl proton region (5 4.5-6.8 p.p.m.). Chemical shifts and coupling constants of representative examples of azepines and their hydro, oxo, benzo and dibenzo derivatives are listed in Table 2. 

One of the facets of azepine chemistry that has attracted organic chemists over the past two decades has been the synthesis of, and search for aromatic character in, the so-called azatropones and azatropolones. To this end all the monocyclic azepin-2-, -3- and -4-ones, several diones, and their benzo and dibenzo derivatives have been prepared. 

In common with many other nitrogen heterocycles azepin-2-ones and their benzo and dibenzo derivatives exist solely as the amide tautomers (76AHC(S1)554). 

Table 4 pif. Values of Azepines and their Benzo and Dibenzo Derivatives... 

H3C.n J H desipramine [3-(10,11-Dihydro-dibenzo[b,f]azepin-5-yl)-propyl]-methyl-amine, C18H22N2, MW 266.39, [50-47-5] diabetic neuropathy (12.5-150 mg/day for 15 weeks) Max etal., 1992 Sindrup et al., 1990a... 

Dibenzo[b,f]azepine-5-carboxylic acid amide, CisH NzO, MW 236.27, [298-46-4]... 

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