Thieno benzazepines

Several other examples of a thieno benzazepine synthesized from substituted thieno aryls through nitrile ylides have been reported (1994JCS(P1)1193). 

Similar to furo derivatives, cascade ketene imine [2-f2] cycloaddition and palladium catalyzed cyclization gives thieno benzazepines 98 and 99 (X = S) with the fused /i-lactam moiety in 65 and 66% yields, correspondingly (Scheme 18, Section 2.1.2 (1995TL9053)). 

Similar to the furobenzazepine derivatives (Scheme 17, Section 2.1.2), thieno benzazepines 96 and 97 (X = S) were synthesized in good yields by a multistep procedure involving in situ generation of azomethine imines from thiene-3-carbaldehyde and A/ ,N -disubstituted hydrazines followed by cycloaddition to... 

Thieno benzazepine 109 was synthesized in moderate yield by oxidative biaryl-coupling using the hypervalent iodine reagent phenyliodine(lll)bis (trifluoroacetate) (FIFA) and BF3 OEt2 as the activating agent in methylene chloride (Equation (16) (2002X8581)). 

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... 

The 2-(2-pheriylvinyl) derivative 18 and the thienyl compound 20 cyclize exclusively at the alkene carbon, and at the thiophene ring, to give 3,4-diphenyl-l//-2-benzazepine (19) and 4-phenyl-6-//-thieno[3,2-e]-2-benzazepine (21), respectively.48 A mechanistic rationale for these results has been offered. This method has been extended to the synthesis of 7Z7-pyrido[3,4-t/]-, 7//-pyrido[2,3-t/]- and 77/-pyrido[4,3-r/]benzazepincs and to other thieno- and furo-fused 2-benzazepines.244... 

Dehydration of 9,10-dihydro-4//-thieno[3,2-b]-l-benzazepin-10-ols, e.g. 57, to the thienobenz-azcpines, e.g. 58, is best carried out with neutral alumina in refluxing benzene.137 Dehydration can also be accomplished by heating the alcohol 57 with fumaric acid in ethanol. 

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... 

Several syntheses of thienobenzazepines have been reported in the literature however, they generally require the use of reagents and/or reaction conditions which present challenges on a preparative scale. In this manuscript we describe a new and efficient synthesis of the thieno[2,3-c]benzazepine tricycle that involves a key selective reduction-intramolecular amidation cyclization process and enables large-scale preparation of these important compounds. 

The synthesis of thieno[3,2-c]benzazepine derivative 106b has been reported by Friedel-Crafts intramolecular cyclization of isocyanates 105 (Equation (15) (2002S355)). Noteworthy, lactam 106b is formed in 51% yield, while dione 106a can not be obtained due to the electron-withdrawing effect of the carbonyl group. 

Xhe synthesis of thieno[3,2-c]benzazepine-l,6-dione by treatment of 3-methyl-amino-3-methylthio-l -phenylthioxopropene with 2-hydroxy-l, 4-benzoquinone, which serves as enolizable cyclic ketone, has been reported (2000JOC3690). 

Acid catalysed cyclisation of the substituted furans 20 led to formation of the spiro-systems 21 and 22, the latter being formed preferably <97TL7641>. Other syntheses involving the intermediacy of an oxonium ion include the preparation of thieno[2]azepines <97JHC1494>, l,2,3,4-tetrahydro-5//-l-benzazepine-6,9-quinones <97H(45)1703> and a new synthesis of ( )-cis- and ( )-/ra 8-clavicipitic acid <97T51 >. 

Figure 10.40 Use of the ozonolytic cleavage ofC—C bonds in the reconstitution synthesis of heterocyclic substrates application to the synthesis of7-chloro-2-hydroxyethyl-3,4,5,6-tetra-hydro-4-methyi[2- C]thieno-[4,3,2-e][3]-benzazepine...

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