Dibenzo diazepin-1 -ones

Chemical Name 10-[2-(dimethylamino)ethyl] -5,10-dihydro-5-methyl-11H-dibenzo[b,ej-[1,4] diazepin-11-one hydrocliloride... 

The formation of 5//-dibenzo[r/,/][l,3]diazepin-6(7//)-one (13, R = H) in good yield by fusing biphenyl-2,2 -diamine with urea was reported in 1901177 and has since been extended to the preparation of numerous analogs.178 Selected examples are given yields were generally not reported.177-179... 

The reduction of a dinitro ketone to an azo ketone is best achieved with glucose. 2,2 -Dinitrobenzophenone treated with glucose in methanolic sodium hydroxide at 60° afforded 82% of dibenzo[c,f [i 2]diazepin-l 1-one whereas lithium aluminum hydride yielded 24% of bis(o-nitrophenyl)methanol [575], Conversion of aromatic nitro ketones with a nitro group in the ring into amino ketones has been achieved by means of stannous chloride, which reduced 4-chloro-3-nitroacetophenone to 3-amino-4-chloroacetophenone in 91% yield [178]. A more dependable reagent for this purpose proved to be iron which, in acidic medium, reduced m-nitroacetophenone to m-aminoacetophenone in 80% yield and o-nitrobenzophenone to o-aminobenzophenone in 89% yield (stannous chloride was unsuccessful in the latter case) [903]. Iron has also been used for the reduction of o-nitrochalcone, 3-(o-nitrophenyl)-l-phenyl-2-propen-l-one, to 3-(o-aminophenyl)-l-phenyl-2-propen-l-one in 80% yield [555]. 

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). 

This is the least common method available to synthesize 1,2-diazepines. The reason for this is that there are fewer methods/reactions to form N-N bond. Reductive cyclization of a 1,5-dinitro compound has been used in the preparation of dibenzo[V/]diazepines <1984CHEC(7)593>. A photochemical approach has been used in making the N-N bond of acetylesters of 2,2 -dinitrodiphenylcarbinols in protic solvents, such as isopropanol, to give dibenzo[r-/][l,2]diazepin-ll-one 5-oxides <1996CHEC-II(9)113>. 

The carbonylation of 7V1-(2-iodophenyl)-iV1-methylbenzene-1,2-diamine 91, catalyzed by Pd complexed to a silica-based dendrimer ligand (Gi), provided 5-methyl-5//-dibenzo[A ][l,4]diazepin-ll(10//)-one 92 in excellent yield (Scheme 48) <2005JA14776, CHEC-III(13.06.9.1.8)211>. 

Acetylation of ll-(2,4-dichlorophenyl)-2,3,4,5,10,ll-hexahydro-3,3-dimethyl-lH-dibenzo[fr,e][l,4]diazepin-l-one and its analogues with acetic anhydride gave a series of N-acetyl derivatives, which were evaluated for their HCV inhibitory activity (07WOP196). 

The photolysis of 1 l//-dibenzo[c/][l,2]diazepine in acidified EtOH has given the corresponding dibenzodiazepin-ll-one and minor amounts of 2,2 -diaminobenzophenone and 2,2 -diamino-diphenylmethane <67AJC2229>. Similar treatment of the 3,8 -dichloro- and 3,8 -dibromo-ll/7-dibenzodiazepines, in the same solvent, also affords their 11-ethoxy derivatives (68), which adds support to the proposed photoinduced intermolecular hydride-transfer mechanism <91JIC299>. 

Formation of the a bond has been achieved by irradiation of acetyl esters of 2,2 -dinitrodiphenyl-carbinols in protic solvents, such as Pr OH, to give dibenzo[c/][l,2]diazepin-l 1-one 5-oxides <9IMI 904-05>. The corresponding dibenzo[c/][l,2]diazepin-l l-ones, 2,2 -dinitrobenzophenones, 2-amino-2 -nitrobenzophenones and iV-hydroxyacridones are also formed in varying amounts the reaction becomes more complex in aprotic solvents. 

This methodology with some variations has been utilized in the synthesis of numerous heterocyclic systems, such as heterocycle-fused quinolinone derivatives [391], l,4-benzodiazepin-2-ones [392], benzo-, naphtho- and heterocycle-fused pyrrolo[2,l-c][l,4]diazepines [393], quinolinone or pyrrolidinone derivatives [394], dibenzo[fl,c]phenanthridines [395], thiazolo-fused quinolinones [396], isoindolinone and isoquinolin-2-one derivatives [397], indoline derivatives [398], 5-aroyl-pyrrolidinones [399,400], indazolone derivatives [401,402], substituted indolizidinones [403], 1-arylpyrrolopyrazinones [404], stmcturally diverse... 

In another report, 1,5-benzodiazepines have been obtained from reaction of alk-3-yn-l-ones with 1,2-phenylenediamines in ethanol under microwave heating without the need for any catalyst (14GC1120). A palladium-catalyzed domino reaction between 1,2-phenylenediamines and 10,11-dihydro-5H-dibenzo[fc,e][l,4]diazepines starting from 2-bromobenzyl bromides has also been developed (14EJ04773). 

Efficient domino approaches to multifunctionalized tricyclic fused pyrroles 59 and dibenzo[h,e][l,4]diazepin-l-ones 60 have been established starting from enam-inones 57 with different substitution patterns and arylglyoxal monohydrates 58. The reaction pathway is controlled by the substituent at the N atom in 57. The domino process can easily be performed by simply mixing 58 and N-amino acid enaminones or 3-(2-aminophenylamino)-5,5-dimethylcyclohex-2-enones 57 in the presence of AcOH under microwave irradiation (Scheme 12.21). The reaction occurs within 12-36 min, with water as the second product. A complete anti diastereoselectivity was achieved within the formation of tricyclic fused pyrrole derivatives [42]. 

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