Triazepines, synthesis

The synthesis of 9H-benzo[2,l-e]thiazolo-[2,3-c]-as-triazine (401) was achieved by oxydative cyclization of 2-imino-3-(o-aminophenyl)-4-phenyl-4-thiazoline (718, 719). This latter reacts also with paraformaldehyde in hot toluene yielding 3-phenyl-9H.10H-benzo[l,2-/]thiazolo-[2,3-d][l,3,5]triazepine (402) (720). This heterocyclic sytem is also formed when carboxylic acids replace paraformaldehyde (Scheme 230) (721). 

Triazepine, 5-benzyl-3,7-diaryl-4,6-dihydro-imidazole synthesis from, 5, 497... 

Azido-3-methoxypyridazines 1 are transformed into 6,7-dimethoxy-477-1,2.5-triazepines 3 by irradiation in the presence of sodium methoxide. The reaction proceeds via the unstable 277-tautomers 2, which were detected by NMR spectroscopy and can be trapped as the 2-acetyl derivatives 4 by adding acetyl chloride to the crude photolysate.371 The synthesis fails for azidopyridazines lacking the 3-methoxy substituent. 

Annulated 1,3,5-Triazepines 1,3,5-Benzotriazepines Synthesis by Ring-Closure Reactions... 

Resin bound dipeptides have been used in the parallel synthesis of 3,4,7-trisubstituted 4,5,8,9-tetrahydro-3//-imidazo l, 2-a l, 3,5 triazcpinc-2(7//)-thioncs and Af-alkyl-4,5,7,8-tetrahydro-3//-imidazo[ 1,2-a][l, 3,5]triazepin-2-amines by ring construction methodology <06JCOl27>. 

Reactions of this type are of value in the synthesis of 1,2,4-triazepines fused to various heterocyclic ring systems. Reactants of type (464) combine with /3-keto esters to give products such as (465) (75JHC661, 1095, 79LA639). Similarly compounds of type (466) react with /3-halogenoacyl halides, /3-diketones and /3-keto esters to give a variety of triazepines and triazepinones, e.g. (467) (77AJC2053). 

Concerning the theoretically accessible triazepine systems, the respective 1,2,3-analogues are the least studied. Despite several computational studies published since CHEC(1996), the synthesis of both monocyclic and fused 1,2,3-triazepines remains elusive. 

The synthesis of diaryl-thiazolotriazepines 62 from the reaction of l,2,4-triazepine-3-thiones 63 (1.8 mmol) with 2-haloketones 64 (6.25 mmol) in ethanol under reflux for 2h was described <1999T5909> with the goal of creating new immunomodulating agents (Scheme 5). The starting triazepines were prepared by the addition of thiocyanic acid 65 to the chalcones 66 according to an already known method, followed by reaction of the intermediate 67 with hydrazine. 

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