Benzo thiophenes, ring synthesis

Gold catalyzed reactions are currently enjoying considerable interest, and have also found applications in thiophene ring synthesis. A series of (a-alkoxyalkyl)(o-alkynylphenyl) sulfides 14 was subjected to treatment with catalytic amounts of AuCl, giving the benzo[fe]thiophenes 15 in excellent yields. Some additional, more complex examples were also provided <06AG(E)4473>. 

The first synthesis of the parent compound of the benzo[4,5]thieno[2,3-f]pyrrole ring system 387 <2003T1477> and its derivatives was accomplished using the same synthetic sequence (Scheme 42). Starting with 2-methyl-benzo[ ]thiophene-3-carbaldehyde 388, an intermediate 389 was obtained. Treatment of bromo compound 389 with sodium azide in ethanol led to the stable triazoline 390. 1,3-Dipolar cycloreversion of 390 was induced by a catalytic amount of />-TsOH to give the parent 2//-benzo[4,5]thieno[2,3-c]pyrrole 387. Alternatively, direct treatment of bromo compound 389 with excess ammonia furnished 387 in one step. Compound 387 was treated with di-/-butyl dicarbonate and 4-dimethylaminopyridine (DMAP) to give iV-BOC derivative 391. Reaction of 389 with... 

The above methods for the synthesis of benzo[6]thiophenes involve the fusion of a thiophene ring on to an already existing benzene ring. The alternative approach, i.e., that of building a benzene ring on to a thiophene ring, also has important applications. 

There has probably been more work carried out on the synthesis of indoles than on any other single heterocyclic system and consequently many routes are available ring syntheses of benzo[ >]thiophenes, benzo[ )]furans have been much less studied. It is surprising that the Fischer indole synthesis, now more than a hundred years old, is still widely used - an arylhydrazone is heated with an acid, a multi-step sequence ensues, ammonia is lost and an indole is formed. 

Thiophenes and their Benzo Derivatives Synthesis 2.11.2 RING SYNTHESIS BY FORMATION OF ONE BOND... 

Electrophilic Ring-closure.—Cagniant and co-workers have extended their studies on the synthesis and properties of thiophens with annelated saturated rings to benzo[/ ]thiophen. The 3-benzo[6]thienylthio-acid (356),... 

Benzo[6]thiophene, 4,7-dialkoxy-synthesis, 4, 930 Benzo[6]thiophene, 2,3-dialkyl-synthesis, 4, 877-878 Benzo[6]thiophene, 3 -(dialkylamino)-synthesis, 4, 925 Benzo[c]thiophene, 1,3-diaryl-oxidative ring opening, 4, 768 Benzo[6]thiophene, 2,3-dibromo-reactions, 4, 830... 

Benzo[c]thiophene, 1,3-diphenyl-oxidative ring opening, 4, 768 synthesis, 4, 141-142... 

Castle and co-workers <1996JHC119, 1996JHC185, 1997JHC1597, 1998JHC1441> used 3-chlorothieno [2,3-3]thiophene-2-carbonyl chloride 280 in the synthesis of the appropriate amides, which by oxidative photo-cyclization gave novel polycyclic heterocyclic ring systems thieno[3, 2 4,5]thieno[2,3-f][l,10]phenanthroline 281, thieno[3, 2 4,5]thieno[2,3-f]naphtho[2,iy ]quinoline 282 and thieno[3, 2 4,5]thieno[2,3-f]naphtho[l,2-g]qui-noline 283, thieno[3, 2 4,5]thieno[2,3-f]naphtho[l,2y ]quinoline 284, thieno[3, 2 4,5]thieno[2,3-f]naphtho[l,2 7]-[l,2,4]triazolo[3,4- ]quinoline 286, thieno[3, 2 4,5]thieno[2,3-f]naphtho[l,2-/]tetrazolo[l,5- ]quinoline 288, benzo[ ]thieno[3, 2 4,5]thieno[2,3-f]quinoline 285, benzo /]thieno[3, 2 4,5]thieno[2,3-f]quinoline 287, benzol/] thieno[3, 2 4,5]thieno[2,3-f]tetrazolo[l,5- ]quinoline 289, and benzo[/jthieno[3, 2 4,5]thieno[2.3-f][l,2,4]triazolo[4,3- ]-quinoline 290. 

A concerted elimination-cyclization mechansim, involving a sulfenyl halide in a 1,3-butadiene-1-thio system, is the most probable mechanism for the formation of benzo[6 Jthiophenes from cinnamic acids or 4-aryl-2-butanones by treatment with thionyl chloride. The reactions shown in Scheme 5 have been carefully worked out, and the intermediates isolated (75JOC3037). The unique aspect of this synthesis is the reduction of the sulfinyl chloride (a) by thionyl chloride to form the sulfenyl chloride (b). The intermediate (b) was isolated and converted in pyridine to the 3-chlorobenzo[6]thiophene-2-carbonyl chloride in 36% yield (73TL125). The reaction is probably initiated by a sulfenyl ion attack on the aromatic ring, since it is promoted by electron-releasing groups para to the site of ring closure. For example, when X in (36) was N02, a 23% yield of (37), a mixture of 5-and 7-nitro derivatives, was obtained, but when X in (36) was OMe, a 54% yield of (37) was obtained, contaminated with some 3,4-dichloro-5-methoxybenzo[6]thiophene-2-carboxylic acid. 

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