Dibenz azepine

Similar problems arise with the four isomeric dibenzazepines 4-7. since only 5//-dibenz-[6,d]azepine (4) and 5//-dibenz[/>,./]azepine (7) can be drawn as fully benzenoid ring structures. Even so, 5//-dibenz[/ ,t/]azepines are rare and are known only as the 7-oxo derivatives.4 In contrast, 5//-dibenz[6,e azepine (5) and 6//-dibenz[r,t>]azepine (6) exist only as the 11//- 5a and 5H- 6a isomers, respectively. In fact, there is no chemical or spectrosopic evidence for the isomerization of 5//-dibenz[e,e]azepine,5 or its 6-oxide,6 to the 6//-dibenz[r, e]azcpinc isomer (6). In addition, an X-ray crystal structure of 7-methoxy-5//-dibenz[e,e]azepine supports unequivocally the benzenoid rather than the quinonoid form.7 9//-Tribenz[6,d /]azepine (8) has only recently been prepared.8... 

Surprisingly, X-ray structural analysis of the dark-green, hygroscopic tetrabutylam-monium salt of 5//-dibenz[6,/]azepine reveals that the potentially antiaromatic 5//-dibenz-azepine anion has a less pronounced nonplanar butterfly structure (161° vs. 144 ) than 5H-dibenz[6,/]azepine.243... 

The pharmacologically active and commercially important 5//-dibenz[/>,/]azepines 40 are available by base-catalyzed dehydrobromination of their 5-acyl- 10-bromo-l 0.11-dihydro derivatives 38,118 followed by hydrolysis of the isolable tV-acyl compounds 39 29.119-121... 

Saponification of the a,/ -unsaturated ester 59, prepared by a Reforma tsky reaction on 8-chloro-5-methyl-5//-dibenz[/>,/]azepin-10(ll//)-one, is accompanied by migration of the exocyclic C —C double bond to form the 5W-dibenz[/>,/]azepine 60.72... 

In hot polyphosphoric acid (PPA), 1-arylindoles undergo ring expansion to 5//-dibenz[/>,/]-azepines 14 in modest yields (8 65%).239... 

Mcthyl-5//-dibenz[/>,/ azepinc 5-oxidc (3) is deoxygenatcd rapidly and in high yield to 5-methyl-5//-dibenz[/>,/]azepine (4) by aqueous sodium sulfite, and, less efficiently and accompanied by deniethylation, by heating at 160-170 C for 20 minutes.124... 

Bis(bromomethyl)-5//-dibenz[/), / ]azepines, e.g. 12, prepared by free-radical bromination of the 10,11-dimethyl compound with yV-bromosuccinimide, on treatment with a primary alkyl-amine followed by alkaline hydrolysis, yield l,2,3,8-tetrahydrodibenzo[. /]pyrrolo[3,4-<7]-azepines, e.g. 13, which possess useful pharmacological properties.91,163... 

The heteroaryne 15. produced by treating 5-aeetyI-10-bromo-5//-dibenz[/>,/]azepine (14) with potassium rm-butoxide (see Section 3.2.1.4.2.), has been trapped by cyclohexa-1,3-diene8 and by furan118 as the [4 + 2] cycloadducts 16 and 17, respectively (see also Section 3.2.1.1.1.1.).118... 

Nitroso-5//-dibenz[/>,/]azepine (9, R = NO) is relatively stable to photolysis under argon, whereas in benzene solution in the presence of oxygen, irradiation induces an oxidative Fischer -Hepp-type rearrangement to 2-nitro-5//-dibenz[6,/]azepinc (10, R = N02), accompanied by ring contraction to acridine-9-carbaldehyde184 (see also Section 3.2.2.4.). 

Low yields of the 5-acetyl-l0,11-epoxy derivative 11 (R = Me) are also obtained by oxidation of 5-acetyl-5//-dibenz[/>,/]azepine (10, R = Me) with iodoxybenzene and vanadium(lll) acetylacetonate, and with iodosobenzene and iron(lll) porphyrin.220... 

Dialkyl-5//-dibenz[/>,/]azepines 6 on oxidation with 3-chloroperoxybenzoic acid undergo ring contraction to 9,10-dihydroacridinc-9-carbaldehydes 7.223 In contrast, 5,10,11-trialkyl derivatives 8 yield mixtures of the acridinyl ketones 9 and 10,11-epoxides 10. 

Acetyl-5//-dibenz[/>,/]azepine-10-car bon itrile (17, R = CN) when treated with sodium borohydride undergoes reduction (73 % yield) at the CIO - Cl 1 double bond without reduction of the acetyl or cyano groups.212 However, hydroboration of 5-acetyl-5//-dibenz[/y/]azepine (17, R = H) with diborane in tetrahydrofuran under standard conditions is accompanied by reduction of the acyl function to yield 5-ethyi-10,l l-dihydrodibenz[6,/]azepin-10-ol (18).72... 

Reductions of 5-substituted 10-nitro-5//-dibenz[/ ,/]azepines 19 (R = CN, CONH2) with various reducing agents have been studied in detail. The major products 20 and 21 are summarized in the reaction schemes below.185... 

Nitroso-5//-dibenz[/j,/ azepine (see Section 3.2.1.5.4.1.) in methanolic hydrochloric acid undergoes rearrangement and ring contraction to a mixture of acridine (59%), acridine-9-carbaldehyde (trace), and 2-nitro-5//-dibenz[/ ,/ azepine (3% mp 176-178 C).184 However, in acetone and hydrochloric acid, the aldehyde (57 %) becomes the major product. On thermolysis, (or photolysis in the presence of oxygen), in hydroxylic solvents, the nitroso compound yields mainly acridine (36-76%) together with minor amounts of either 2-nitrodibenzazepine (4-6% by thermolysis) or acridine-9-carbaldehyde (18% by photolysis). However, in non-hydroxylic solvents, e.g. cumene, acridine-9-carbaldehyde (64%) is the major product. 

Only a few polar additions to azepines have been reported of which the most common are the electrophilic additions to the 10,11-bond of 5//-dibenz[ >,/]azepine these have been reviewed (74CRV101). The N-acetyl derivative adds fluoroxypentafluoroethane and the adduct on treatment with sodium hydroxide eliminates HF to yield lV-acetyl-10-perfluoroethoxy-5//-dibenz[6,/]azepine (80JOC4122). 

Furthermore, in the addition of bromine to 44 (in 1,2-dichloroethane, chloroform or carbon tetrachloride, see Scheme 19) to obtain the trans dibromo derivative99 (47), which is found to be in two main conformers100, the formation of the bromonium ion (46) from 5//-dibenz[ >,/]azepine-5-carbonyl chloride (44) is a reversible step. The formation of the bromonium ion (46) follows the association of reagents in the CT complex (45). 49 reacts with hydrogen bromide through the protonated 48, forming" both the dibromo derivative 47 and the olefin 44. The bromonium ion (46) is the probable intermediate... 

We have introduced the concept of homoheteroaromaticity (the equivalent of homoaromaticity [18] for heterocycles) to describe the structure of some cations obtained by protonation of l//-azepine (4) and 5//-dibenz[/ ,/]azepine (5). B3LYP/6-311++G, GIAO, and NICS calculations together with some NMR experiments lead us to conclude that the neutral molecules are antiaromatic and that the cations 6 and 7 are homoaromatic [22],... 

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