1,2-Diazepines

Synthesis of Tetracyclic 2,3-Dihydro-1,3-diazepines from a Dinitrodibenzothiophene Derivative

“…The reaction mixture was left to stir at room temperature for 2.5 h and then poured over ice to produce a brown precipitate, which was filtered off and washed with diethyl ether (50 mL) and then hexane (50 mL) to yield 4 as a pale brown solid (12.7 g, 86%). The compound was used without further purification: mp 230 °C (dec); 1 H NMR (400 MHz, DMSO-d 6 , ppm) δ 8.96 (2H, d, J = 1.0 Hz, H 2/8 ), 8.81 (2H, d, J = 1.0 Hz, H 4/6 ), 8.61 (2H, s, NH), 8.12 (2H, s, NH); 13 3,7-Dicyano-1,9-dinitro-5,5-dioxo-5H-dibenzo[b,d]thiophene (5). A solution of 4 (1.60 g, 4.08 mmol) in phosphorus oxychloride (40 mL) was heated to reflux for 3 h. The resulting dark orange solution was cooled to room temperature and quenched slowly with warm water.…”

“…Developing new routes to underexplored heterocyclic motifs is a fundamental driving force in organic chemistry and is essential to identifying new structures of medicinal or technological value. Diazepines are of major pharmaceutical importance. − 1,2-Benzodiazepines and 1,4-benzodiazepines in particular comprise entire classes of drugs, including the antianxiety medications tofisopam (strictly a 2,3-diazepine) and diazepam. − 1,3-Diazepines, and the saturated analogues 1,3-diazepanes, are less prevalent; however they have been studied as HIV protease inhibitors, − as anticancer − and antiviral agents, ,− and also as N -heterocyclic carbene ligands. , In comparison with 1,2- and 1,4-diazepines, routes to 1,3-diazepines are less clearly established. Since the last comprehensive survey of their synthesis only a handful of new synthetic approaches have been reported for monocyclic, − singly − or doubly ring-fused 1,3-diazepines. − …”

Dearomatization of Pyridines: Photochemical Skeletal Enlargement for the Synthesis of 1,2-Diazepines

“…Heterocyclic scaffolds are ubiquitous in bioactive molecules and particularly coveted in drug design as they confer selectivity and valuable properties to a potential drug candidate. − Among them, pyridine-containing compounds could be found in a vast part of the FDA-approved biorelevant molecules (Figure A). − Indeed, this aromatic core can be prepared and modified in many efficient ways. , On the other hand, 7-membered ring azaheterocycles, like 1,2-diazepines, are much less studied . The two heterocycles only differ by one nitrogen atom, yet they contrast sharply.…”

“…The two heterocycles only differ by one nitrogen atom, yet they contrast sharply. Reported syntheses of 1,2-diazepines exclusively rely on the combination of well-designed 1,5-dielectrophiles and hydrazine, as the N–N bond formation is reputed to be challenging . The latter induces side reactivities such as oligomerization, polyalkylation, or even potential hydrolysis of the substrate.…”

1,3‐Diazepine: A privileged scaffold in medicinal chemistry

“…Although 1,4‐diazepines represent the most significant class of compounds in terms of clinical use, 1,2‐diazepines and 1,5‐diazepines have also shown interesting activities 13,14 . For example, cilazapril, a 1,2‐diazepine derivative, is an angiotensin‐converting enzyme inhibitor used for the treatment of hypertension and congestive heart failure 15 ; 1,2‐diazepines (strictly benzo‐2,3‐diazepines), that is, tofispam, nérisopam, girisopam, showed potent anxiolytic and antipsychotic properties or are used in the treatment of epilepsy (talampanel) 16 .…”