Benzo thieno 2,3-£ pyridines

Reviews have appeared dealing with the synthesis of 6i/-pyrido[4,3- ]-carbazoles, thieno-pyridines, and imidazo-pyridines (and their benzo-analogues) having a bridgehead nitrogen atom. ... 

Eberbach has shown that pyrolysis of the system 39, in which both A and B represent benzene rings, the product is the stable dihydrodibenzo[c,e]oxepine 40, (A,B = benzo), in which the intermediate ylide undegoes a 1,7-electrocyclisation followed by a [1,5] H shift (Scheme 9) <85CB4035>. This work has now been extended by Sharp to include systems where B is a thiophene or pyridine, offering a route to the corresponding thieno- and pyrido-benzoxepines <96JCS(P1)515>. 

Three different fused systems have been reported in the literature thieno[3, 2 4,5]thieno[2,3-c]pyridine (f/r-thiophenes), thieno[2, 3 4,5]thieno[2,3-c]pyridine (tram- thiophenes) and thicno[3,2-g]thicno [3,2-d pyridine derivatives. So far, the parent thienothienopyridines have only been prepared via the corresponding pyrylium salts (see below) all others are benzo or extended carbocyclic derivatives, for example, thienothienoquinolines. 

Electrophilic substitution in benzo[fe]thieno- and benzo[fe]furo-[2,3-c]pyridines (2) occurs mainly at the 6-position, although when this position is blocked by Cl in a related structure 5-,7-, and 8-substituted products are formed. The usefulness of triflu-oromethanesulfonic acid as a new solvent with CFCI3 for the reaction of fluorine with aromatics has been explored. Fluorobenzene gives 1,4-difluorobenzene (31%) and 1,2-difluorobenzene (7%) instead of the addition products mainly observed when the acid is absent 1,2- and 1,3- but not 1,4-difluorobenzene undergo further substitution at appropriate acidity. 

In 1972 Wright prepared 3-chlorothieno[3,2-6]thiophene-2-carbonyl chloride (94) in 11-13% yield by heating 3-(2-thienyl)acrylic acid, thionyl chloride, and pyridine, a method of synthesis of benzo[6]-thiophene-2-carbonyl chloride derivatives. " Methyl 3,5-dichloro-thieno[3,2-6]thiophene-2-carboxylate (95) and methyl 2-chloro-3-(5-chloro-2-thienyl)acrylate were also isolated. When fte reaction was carried out in refluxing toluene or chlorobenzene, the acid chloride (94)... 

As in the case of the furopyridines (Section 3.17.2.1.1), there are six thienopyridine systems (Scheme 59) those derived from benzo[Z> ]thiophene (258-261) and those that are analogs of benzo[c]thiophene (262-264). The chemistry of thienopyridines has previously been reviewed both as an overview (72IJS(B)(7)309) and in a detailed manner (77AHC(2l)65, 81H(15)1285). The latter article presents a correlation of the chemistries of thieno[2,3-/ ]pyridine and thieno[3,2-6]pyridine with those of benzo[6]thiophene and quinoline. 

The pKa values for the four readily available thienopyridines (258-261) have been determined (Table 9). As can be seen from these data, the isoquinoline analogs are stronger bases than the quinoline analogs the same is true for isoquinoline and quinoline. The UV data of the benzo[6]thiophene analogs (258-261) (Table 10) show a considerable similarity to that of quinoline (258, 261) and isoquinoline (259,260). As expected, the spectra of thieno-[3,4-6]- and -[3,4-c]-pyridine differ from the parent compounds the colors of (262) and (263) are probably due to their long-wavelength maxima. 

O-Acyl derivatives of thiohydroxamic esters (Barton esters) react with benzynes to afford a tricyclic thiophene ring system thus the pyridine derivative 30 gives benzo[4,5]thieno[2,3-A pyridines 31 (Scheme 14) <2002JOC3409, CHEC-III(3.11.3.3)900>. 

The derivatives 22 <2005FA727> exploit the / -lactam antibiotic motif for antimicrobial activity benzo[/ ]thiophenes such as the amides 23 <2004JIC694, 2004T11821, 2005PS601> or the thieno[2,3-/ ]pyridines 24 <2005PS1815> have also been tested in that respect. 

Scheme 45 Coupling-addition-nucleophilic aromatic substitution three-component synthesis of 4//-thiochromen-4-ones 82, 4/f-thiopyrano[2,3-i)]pyridin-4-ones 83, 2-chloro-4/f-thieno[2,3-b] thiopyran-4-ones 84, or 7//-benzo-[b]thieno[3,2-i)]thiopyran-7-ones 85...

Bonini, C., D Auria, M., Funicello, M., Romaniello, G. Novel N-(2-benzo[b]thienyl)iminophosphoranes and their use in the synthesis of benzo[b]thieno[2,3-b]pyridines. Tetrahedron 2002, 58, 3507-3512. 

The condensation of thioglycolates or a-thioketones onto nitriles, known as the Thorpe-Ziegler cyelization, can be employed to synthesize p-aminothiophenes. This basic strategy was utilized to synthesize a-(methylthio)thiophene 38 , 2,4-diaminothiophene 39 , benzo[fc]thiophene 40 , thieno[2,3-c]pyridazine 41 , thieno[3",2" 5, 6 ]pyrido[2, 3 4,5]thieno[2,3-c]pyridazine 42 , thieno[2,3-i ]pyridine 43 , and thieno[3,2-c]pyran-4-one 44 . 

Biehl s group [97] has developed an efficient syntesis of benzo[4,5]thieno [2,3- ]pyridines and appropriate naphthyl-analogues by reaction of in situ generated benzyne with Barton esters. For example, when the acetone solution of anthranilic acid (58) was added dropwise to the refluxing mixture of the Barton ester 527 and isopentyl nitrite in dichloromethane, after an additional 3-h refluxing period, the respective benzo[4,5]thieno[2,3-A]pyridine (528) was obtained in 52% yield. Scheme 52. 

Normally, decompositions of azides in hydrogen-rich solvents are avoided in order to minimize the formation of products based on triplet nitrene. Surprising, therefore, is the report that 6i/-dibenzo[c ,e][l,2]thiazine 5,5-dioxide (335) is obtained in optimum yield (80.6%) from the thermolysis of biphenyl-2-sulphonyl azide in cyclohexane at 120 Decomposition of o-(2-thienyl)benzenesul-phonyl azide under similar conditions furnishes the thieno[3,2-c]benzo-l,2-thiazine dioxide (336), in practicable yield (61%). Whereas, in POCla-pyridine... 

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