Benzo l,4-diazepin

The calculated interconversion barriers between the M- and P-forms of 3,4-dihvdro-l//-benzo[l,4]diazepin-2,5-diones depend on the size of the N-l substituent but not the C-3 and N-4 substituents <2004JST37>. The... 

Highly diastereoselective alkylation at C-2 of benzo-l,4-diazepin-3-ones 41 was accomplished in 40-85% chemical yield using an (R)-phenylglycinol moiety at N-4, as the chirality-inducing element (Scheme 10) <2005EJ01590>. The optimum conditions involve deprotonation of 41 with 2 equiv of -BuLi at — 40 °C and alkylation at — 78 °C to give products 42 with 86-96% de. A single crystal X-ray diffraction analysis of the methylated derivative determined that the major product formed was the 2-(R)-isomer, as depicted in the product 42. 

Alkylation of the benzo-l,4-diazepine-2,5-dione 44 occurred in good chemical yield but with moderate and unpredictable diastereoselection (Scheme 13) <1999JOC2914>. Although both the yield and de were improved in the presence of excess HMPA, the inclusion of LiCl, as an additive, led to a significant erosion of de. These results could not be rationalized after theoretical analysis of transition state geometries. 

Chloroketene adds to the imine moiety of substituted 2,3-dihydro-17/-benzo-l,4-diazepines with excellent regio-and diastereoselectivity to afford the (2 S, 2ai ,4i )-fused /3-lactam adduct and its enantiomer (Scheme 22)... 

A sequence comprising an Oppenauer-type oxidation, intramolecular imine formation, and reduction, a process mediated by the iridium catalyst [Cp hG 2]2 and K2C03 in toluene at 120 °C for several days, afforded the structurally simple l-methyl-2,3,4,5-tetrahydro-177-benzo[l,4]diazepine in 68% yield from iV-(2-aminophenyl)-(Af-methylamino)propan-l-ol (Scheme 68) <2006TL6899>. 

The reaction of ethyl 2-phenyl-4//-furo[3,2-/>]pyrrole-5-carboxylate (94) with 2-nitrobenzyl-oromide afforded ethyl 4-(2-nitrobenzyl)-2-phenylfuro[3,2-6]pyrrole-5-carboxylate (269) under conditions of phase transfer catalysis by utilization of sodium carbonate and tetrabutylammonium bromide. This product (269) was hydrogenated using palladium-on-charcoal catalyst to give the amine (270), which cyclized in the presence of 2-hydroxypyridine to give 2-phenylfuro[2, 3 4,5]pyrrolo[2,l-c]benzo[l,4]diazepin-l 1-one (271) <92CCC1487>. 

Scheme 30 Coupling-addition-cyclocondensation three-component synthesis of benzo[ >][l,4] diazepines 51...

Smithen, C. E., Thomas, W. A. Peptido-aminobenzophenones-novel latentiated benzo-l,4-diazepines. Experientia 1977, 33,1492-1493. 

There has been a slight decrease in the total number of papers and patents this year, due in particular to a slackening in the flood of patents concerned with benzo[l,4]diazepines and related systems that are of potential pharmacological value. However, interest in 1,2- and 1,3-diazepines and in oxepin chemistry continues to increase and there has been a welcome upswing in the number of papers concerned with systems containing three heteroatoms, although this is still an area with much unexplored territory. 

Diazepines were reviewed in a previous volume in this series in 1967,1 in a chapter which dealt with the whole range of diazepines. The present chapter and the succeeding one in this volume deal with two particular classes of diazepines, the 2,3-dihydro- and 2,3-benzo-l, 4-diazepines. The literature is covered to the end of 1972, with some later references. 

Currie reported that 7-chloro-2-methylamino-5-phenyl-3//-benzo-l,4 diazepine-4-oxide hydrochloride (methaminodiazepoxide hydrochloride, chlordiazepoxide hydrochloride. Librium), possesses oedema inhibitory, anti-inflammatory and analgesic effects in rats similar to those of compounds such as amidopyrine and phenylbutazone. In view of these results, the compound was subjected to clinical trial in rheumatoid arthritis and was found to have neither antirheumatic nor analgesic properties in doses up to 200 mg daily. 

Dihydro-5-methoxy-l//-benzo-l,4-diazepine (70) was acylated on N-1 with acetic anhydride and the anion generated on deprotonation of N-1 with n-butyl lithium reacted normally with methyl... 

The 4-hydroxy compound (108) formed on addition of an aryl Grignard reagent to 7-chloro-2-methoxy-3/f-benzo-l,4-diazepine 4-oxide can be dehydrated by heating either with phenyl isocyanate or V,V -dimethylpiperazine. Dehydration with phenyl isocyanate gave the 57/-isomer (109) while heating with V,V -dimethylpiperazine furnished the 3/7-isomer (110). Compound (109) could also be converted into the (110) on heating with V,V -dimethylpiperazine <77ACS(B)70l>. 

Both of these pathways have been exploited synthetically, providing novel routes to fervenulins (60), s (involving nucleophilic attack by acyl hydrazines), lumazine (61) s and benzo-l,4-diazepines (62). s ... 

T3506). Similarly, 2-halobenzaldehydes, isonitriles, amines, and propar-gylic acids underwent Ugi reaction, then copper(I)-catalyzed alkyne—azide 1,3-dipolar cycloaddition, and then intramolecular Ullmann-type triazole N-arylation to afford triazolo-flised benzodiazepines such as 136 (13EJ01223). Similar reactions involving a post-Ugi lactamization or a post-Ugi intramolecular imination process delivered benzo-l,4-diazepin-2,5-dione derivatives or 4,5-dihydro-3H-l,4-benzodiazepine derivatives (13ACO202,13T9056). 

Very recently, the synthesis of benzo-l,4-diazepin-2,5-diones was reported, using the Ugi-4CR postmodification... 

Palimkar SS, Lahoti RJ, Srinivasan KV (2007) A novel one-pot three-component synthesis of 2,4-disubstituted-3 77-benzo[(>]-[l,4]-diazepines in water. Green Chem 9 146-152... 

Ohta et al. (2008) synthesized indole-fused benzo-l,4-diazepines by copper catalyzed domino three component coupling, indole formation and N-arylation under microwave irradiation from a simple N-mesyl-2-ethynylaniline at 170"C for 20-40 min. 

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