1.4- Diazepine-4-oxides

Me Librium). Dimethylamine, on the other hand, produced a mixture of the diazepine oxide (106 R = = Me) together with the normal... 

R2 = Me Librium). Dimethylamine, on the other hand, produced a mixture of the diazepine oxide (106 R1 = R2 = Me) together with the normal substitution product (107 R = NMe2), and piperidine, cyclohexylamine, and mercaptans formed the normal products (107 R = piperidyl, NHC6H, and SR1). The polarizability of the nucleophile appeared to be more important than its steric properties.238 The reverse transformation was brought about by dilute aqueous acid, which in the presence of an aliphatic aldehyde converted 106 (R1 = H R2 = Me) into the aldehyde adduct of 6-chloro-2-methylamino-4-phenylquinazoline 3-oxide.239 In the absence of an aldehyde, or with nitrous acid, 106 (R1 = H R2 = Me) produced 6-chloro-4-hydroxy-2-hydroxyiminomethyl-3-methyl-4-phenyl-3,4-dihydroquinazoline.240 Simi-... 

The diazepine 26 reacts with the stable nitrile oxide 27 to yield the cycloadduct 28, accompanied by a trace of the rearranged adduct 29.102... 

Dibenzo[l, 2]diazepines are oxygenated to /V-oxides by peracetic acid e.g. formation of 2 from... 

Dichloro-ll//-dibenzo[c,/]]l,2 diazepine 5-Oxide (2a) Typical Procedure 149... 

Dipolar cycloaddition of benzonitrile oxide to 5-methoxy-6-methyl-6FM,4-diazepine results in a l,2,4-oxadiazolo[4,5-d][l,4]diazepine.189... 

Another dihydro derivative has been described in connection with medicinal chemical studies. Thus, reaction of 2-(chloromethyl)quinazoline-3-oxide (3) with hydrazine gives hydr-oxytriazocinamine 4 (and not a diazepine derivative as originally assigned), vigorous acetylation of which results in a rearrangement to give oxazolotriazocine 5.10... 

Fluorinated 1,2-diazepines (23) can be prepared by the thermolysis of 2,4,6-trimethylphenyl azo compounds with elimination of HF from the Me and F ortho to the azo linkage [84CC832 88JFC(41)439]. The oxidation of these unsymmetrical diareno-1,2-diazepines gave N-oxides and diazepi-nones, depending on the oxidant [89JCS(P1)1117]. 

Continuing his studies on the metallation of tetrahydro-2-benzazepine formamidines, Meyers has now shown that the previously unsuccessful deprotonation of 1-alkyl derivatives can be achieved with sec-butyllithium at -40 °C <96H(42)475>. In this way 1,1-dialkylated derivatives are now accessible. The preparation of 3//-benzazepines by chemical oxidation of 2,5- and 2,3-dihydro-l/f-l-benzazepines has been reported <96T4423>. 3Af-Diazepines are also formed by rearrangement of the 5//-tautomers which had been previously reported to be the products of electrochemical oxidation of 2,5-dihydro-lAf-l-benzazepine <95T9611>. The synthesis and radical trapping activities of a number of benzazepine derived nitrones have been reported <96T6519, 96JBC3097>. 

The ylide 44, prepared from the corresponding diazine and tetracyanoethylene oxide, rearranges in methanol the give the 1,3-diazepine 45 <96TL1587>. The x-ray geometry for 45 is reported. 

Single crystal X-ray analysis definitively assigned different structures to products of oxidative cyclization of 58 as pyrazolo 1,2-/z][ l,2]diazepin-5(3//)-onc 59 <1984ZNB187> and pyrazolo[l,2-tf]pyrazol-l(5//)-onc 60 <1997ZNB994>, depending on the character of the R2 substituent. 

A high yield approach to the hexahydropyrrolo[3,2-e [l,4]diazepine-2,5-diones, 105 and their tetrahydrofuro analogues, 106, based on rearrangements of cyclopropylketimines and the cyclopropylketones, derived by acid hydrolysis, have been described. Thermolysis followed by DDQ oxidation of the unstable dihydro intermediates then gave compounds 105 (eg. R1 = Me, R2 = i-Bu) and 106 (eg. R = 4-Cl(C6H4)CH2) . 

Reactions of 2,3-dihydro-17/-1,4-diazepines with mesitonitrile oxide proceed with site- and regiospecific 1,3-dipolar cycloaddition leading to bis[ 1,2,4] oxadiazolo[l,4]diazepine derivatives 160 (326). Of the three compounds 160 only the one with R = R = Ph is formed with trails arranged substituents. The two other products (R = R = Me and R = Me, R = Ph) are mixtures of diastereoiso-mers. The heterotricyclic 6,1 Oa, 11,11 a-tetrahydro-5//-bis[ 1,2,4]oxadiazolo[4,5-d 5 -g][, A diiazeipm.e structure 160 of the obtained bis-adducts indicates that the hetero double bonds are much more reactive than the olefinic ones. No evidence for the formation of monoadducts was obtained. 

Reactions of 1,2-diazepines with nitrile oxides are sometimes difficult to elucidate because they give mixtures (328) or unexpected products. Thus, reactions of 3-methyl- and 3,7-dimethyl-1,2-diazepines with mesitonitrile oxide leads to 5,10-dioxa-l,2,4,ll-tetrazatricyclo[7,3,l,02,6]trideca-3,7,l 1-triene derivatives 162 (R = H, Me, respectively) (329). Such structures were determined by X-ray diffraction studies (330). 

Amino methyl substituted pyrrolo-benzodiazepine 215 forms a cyclic aminal with aldehydes that can be further oxidized with Mn02 to fused 3-substituted imidazole 216. Alternatively, cyclic imine 217 can be submitted to TosMlC cycli-zation to afford unsubstituted 9H-benzo[e]imidazo[5,l-c]pyrrolo[l,2-fl][l,4]-diazepine 218 (Scheme 45, Section 3.1.1.2 (1993JHC749)). 

The UV irradiation of A-oxides of diazepines of type (19 R1 = R2 = Ar) induced [ 2S+ 2S] cyclization and subsequent ring opening to give a d azo ketone (69JA2818,72JA3955). 

The unstable dibenz[c,/][l,2]oxazepines (312 R = CN, Cl) have been isolated as the major products of the UV irradiation of 9-cyano- and 9-chloro-acridine 10-oxides (310) in benzene (c/. the analogous Af-imide to 1,2-diazepine conversion on p. 598). Although none of the oxaziridine tautomer (311) was detectable by UV spectroscopy, the subsequent deoxygenation of (312) to acridine suggests the existence of a thermal equilibrium between (311) and (312) (79T1273). These dibenzo compounds (312) are the only fully unsaturated oxazepines yet isolated but the 2,3-benzoxazepin-l-one system (314) has recently been prepared by the reaction of benzonitrile oxide with the benzopyranone (313) (80JCS(Pl)846). 

A number of monocyclic and benzo-annelated examples of 1,2- and 1,3-thiazepines have been prepared but there has been little systematic study of these systems. The interesting photochemical interconversions of pyridine N-imides into 1,2- and 1,3-diazepines and of pyridine Af-oxides into 1,2- and 1,3-oxazepines regrettably lack parallels in thiazepine chemistry. There has been more interest in 1,4-thiazepines, as both rearrangement products and possible biogenetic precursors for penicillins and because of the pharmacological value of the benzo- and dibenzo-[l,4]thiazepines as antidepressants and coronary vasodilators. The only review (70ZC361) is excellent but not very recent. 

Several 1,4,5-benzotriazocines have been described in connection with medicinal chemical studies. The reaction of 2-chloromethylquinazoline oxide (313) with hydrazine gives the hydroxylaminotriazocine (314) and not a diazepine as originally assigned (73CPB2375). Vigorous acetylation of (314) causes a Wolff-Semmler type rearrangement to give the oxazolotriazocine (315). 

The 1,5-benzodiazepine 40 on irradiation in benzene under oxygen undergoes oxidative ring contraction to 2-benzoyl-3-methyl-quinoxaline.42 Similarly, photolysis of 7-chloro-2-methylamino-5-phenyl-3//-l,4-benzodiazepine-4-oxide (41) in benzene yields the N-benzoylquinoxaline 42. Related ring contractions of diazepines to reduced quinoxalines have also been observed.43... 

A six-membered ring is formed in the reduction of 2-nitrobiphenyl-2 -carboxylic acid68 or 6,6 -dinitrobiphenyl-2,2 -dicarboxylic acid.69 In the former case a phenanthridine is formed, in the latter a 4,9-diazapyrene. Similarly, a seven-membered ring is obtained when 2-nitro-2 -isothiocyano-biphenyl (15) is reduced in acidic solution with the formation of 6-mercapto-dibenzo[d/]-l,3-diazepine 3-oxide (16)70 [Eq. (28)]. 

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