Thieno azepines

Chemical Name 5-(o-Chlorophenyl)-7-ethyl-1,3-dihydro-1-methyl-1H-thieno[2,3-e] -1,4-di-azepin-2-one... 

X-ray analysis of 2-methoxy-4-hydroxy-5//-l-benzazepin-5-one (a benzazatropolone), prepared by methylation of the corresponding 4-hydroxy-l-benzazepin-2,5-dione with Meerwein s reagent, demonstrates the presence of a planar seven-membered ring but, in contrast to tropolone, little 71-electron delocalization.17 Likewise, ll//-dibenz[f>,e]azepin-ll-ones display no significant aromatic character.18 In contrast, 7-chloro-8//-thieno[3,2-c]azepin-8-one (12) has azepine ring hydrogen resonances at 8.7 and 9.02 ppm that indicate a substantial contribution from the polar zwitterionic mesomer 13.19... 

Chloro-8//-thieno[3,2-c]azepin-8-one (23), which on the basis of its HNMR spectrum appears to exist as the polar mesomer 24, is obtained in 80% yield by treating the 4,5-dihydro-derivative 22 successively with rm-butyl hypochlorite in cold dichloromethane, and triethylamine.19... 

In contrast to 6-azidobenzo[/)]thiophene, which yields only benzo[i]thiophen-6-amine (9 %) and JVh,Ar(1-diethylbenzo[/)]thiopheiie-6,7-diamine (25 % bp 175-177 C/0.7 Torr), 6-azido-2,3-dibromobcnzojhjthiophene (1 a, R = R2 = Br) on irradiation in diethylamine in the presence of pyrene, a triplet nitrene quenching agent, yields a mixture of 2,3-dibromo-./V6,./V6-diethyl-benzo[5]thiophene-6,7-diamine (2a, R1 = R2 = Br 13%) and the 8W-thieno[2,3-r]azepine 3a.14<1 Likewise, methyl 6-azidobenzo[6]thiophene-2-carboxylate (lb, R1 = C02Me R2 = H) yields the thienoazepine ester 3b.147... 

Reductions of 5//-dibenz[/j,/]azepines to their 10,11-dihydro derivatives have been accomplished in high yield with sodium in ethanol,29 133 with copper(II) chromite (2CuO Cr203) and barium carbonate,224 with 5 % palladium on charcoal29 or platinum(IV) oxide30 in ethanol, and with magnesium in methanol.225 4//-Thieno[3,2-/)][1]benzazepine is reduced similarly with hydrogen and palladium on charcoal in ethanol.137... 

The thienodiazepinedione 2 similarly gives 7-ethyl-5-methyl-l-phenyl-l//-thieno 2.3-7>][l, 4]di-azepine-2.4(3//,5//)-dione (3).307... 

Tetracyclic benzo[/]-4-oxopyrrolo[l,2-fl]thieno[3,2-c]azepine 103a, as well as its piperidone homolog 103b, can be prepared through intramolecular N-acyliminium ion cyclization of hydroxylactams 102 (Scheme 20 (2001 HI 519)). 

Construction of the azepine ring by C-N bond formation. Aranapakam et al. synthesized 5,10-dihydro-4H-benzo[l7]thieno[2,3-e]azepine 111 and 4H-benzo[ 7]thieno[3,2-e]azepin-10(9H)-one 113 (X = CO) starting from the corresponding tributylstannyl derivatives 110 and 112, which react with 2-nitrobenzyl bromide and [(Ph)3P]4Pd. Sequential deprotection and reductive cyclization were carried out in one step with zinc and aqueous acetic acid (Scheme 22 (1999BMCL1733)). 

The palladium(O) catalysed tandem cyclisation of a bromoallene tethered with a sulfamide group 124 gives bicyclic azepines 125. The analogous reaction with Af-tethered bromoallene sulfamide 126 afforded bicyclic diazepine 127 <07CEJ1692>. Condensation of thiaisatoic anhydride with -amino acids proved to be a straightforward method for the synthesis of thieno[3,2-< ][l,4]diazcpin-2,5-dionc analogues 128 <07JOC2662>. 

Several unique heterocyclic fused-1,2,4-triazole structures have been published. Pyridine amination of 216 with O-mesitylenesulfonylhydroxylamine followed by condensation with various aryl and heterocyclic aldehydes and subsequent cyclization and oxidation gave triazolopyridines 217 <03TL1675>. Triazolopyridines 217 were utilized in the direct conversion to the triazolopyridine amides 218 with methylaluminoxane premixed with amines in a combinatorial library synthesis. A convenient synthesis of novel 4-(l,2,4-triazol-l-yl)-2-pyrazolines and their derivatives has been reported <03SC1449>. A novel triheterocyclic ring system, thieno[2,3-y][l,2,4]triazolo[l,5-a]azepines, has been published <03S1231>. 

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