Heterocyclic synthesis thiophene derivatives

In connection with an investigation of the fluorescent characteristics of derivatives of 2,2 -bithienyls, a number of heterocyclic substituted thiophen derivatives, such as (199)—(204) and their formyl derivatives, have been prepared. The quinoline derivatives were obtained from the appropriate 2-lithiobithienyl and quinoline, whereas the benzimidazolyl, benzoxazolyl, and benzothiazolyl derivatives were prepared by the condensation of a cyanothiophen or 5-cyano-2,2 -bithienyl with the appropriate aniline derivative. (204) was prepared through a Fischer indole synthesis. ... 

Studies on the Chemistry of Thienoannulated 0,N- and S,N-Containing Heterocycles. 1. Nucleophilic Substitution Reactions on Chlorinated Thiophene Derivatives as a Basis for the Synthesis of Thienoannulated 0,N- and S,N-Heterocycles, Puschmann, I. Erker, T. Heterocycles 1993,36,1323. See also Studies on the Chemistry of Thienoanellated 0,N- and S,N-Containing Heterocycles. II. Synthesis on Thieno-Dilthiazem Analogs, Puschmann, 1. Erker, T. Heterocycles 1995, 41, 709. 

Resins based on Meldrum s acid chemistry (resin bound cyclic malonic acid ester) have been described for the synthesis of thiophene derivatives (Figure 15.5). Release and heterocycle formation was performed in NaOMe/MeOH at reflux for... 

Useful reviews on redox transformations of thiophen derivatives (179 references), on the stereochemistry of carbonyl derivatives of five-membered heterocycles (257 references), on synthetic approaches to dihydrothiophens (135 references), and on biosteric thiophens" have been published. Aspects of thiophen chemistry have been treated in reviews on the synthesis of heterocycles by thermal [2 + 2] cycloaddition reactions of acetylenes and on aspects and perspectives of organic heterocyclic chemistry. A review comparing the chemistry of thieno[2,3-h]- and thieno [3,2-i ]-thiophen with that of benzo[ft] thiophen and quinoline has been published. In Advances in Heterocyclic Chemistry, the development of benzo[6] thiophen from 1968 to 1980 and of selenophen from 1970 to 1980 was presented. Other aspects of thiophen chemistry are treated in chapters on Dewar Heterocycles," on Cyclizations under Vilsmeier Conditions, on Polyfluoroheteroaromatic Compounds, and on Reactions of Benzyne with Heterocyclic Compounds. " Several dissertations treating various aspects of thiophen chemistry have appeared. " ... 

Several routes involving thiophene ring synthesis towards more complex heterocycle fused thiophene systems should also be mentioned. Thus for example, the alkaloid thienodolin 56 has been prepared by reaction of l-(/ert-butoxycarbonyl)-2,6-dichloroindole-3-carboxaldehyde with 2-mercaptoacetamide <04EJO2589>, while a double cyclization of 2,6-dichloropyridine-3,5-dicarbonitrile or the corresponding pyrazine derivative with ethyl 2-... 

A useful reaction for the synthesis of unsaturated seven-membered heterocycles is the (2 + 2)-cycloaddition of heteroaromatic compounds, e.g., 1 //-pyrrole, furan, or thiophene derivatives, with acetylenes. In combination with a subsequent intramolecular (2 + 2)-cycloreversion (Section IV,B,2) of the annulated cyclobutene moiety, ring enlargement with two carbon atoms can be achieved. 1-Heterocycloheptatrienes, such as benzol6]azepines,26,27,65,66 benzo[fc]oxepins,67,68 benzo[6]-thiepins,69,70 and thiepins,18,71 have been successfully prepared in this way other routes are either nonexistent or laborious.72 In these compounds the reacting carbon-carbon double bond constitutes part of a (4n + 2)7r-electron system and in the (2 + 2)-cycloaddition the resonance energy of the aromatic nucleus is lost. Just like the nonaromatic heterocycles, heteroaromatic compounds have been reported to undergo (2 + 2)-cycloaddition reactions both with electron-deficient and with electron-rich acetylenes. 

The present review includes data on the synthesis and chemical properties of the fluorine containing derivatives of furan, thiophene, selenophene, phospholene, and hve-membered heterocycles with two or more oxygen and sulfur atoms pubhshed prior 2007. Every section starts with discussion on the synthetic methods for unsaturated heterocycles (furan, thiophene etc.) and is followed by synthesis and transformations of dihydro and tetrahydro derivatives. 

For isomeric thienothiophenes, both general methods of synthesis and original procedures applicable only to the preparation of particular types of compounds have been developed. In recent years, along with conventional methods based on thiophene derivatives as substrates, other approaches using, in particular, cyclopropenethiones, dithiynes and dithiolium salts have been successfully designed. A special section in this review deals with high-temperature synthesis of annulated thienothiophenes and procedures used for the preparation of particular representatives of this class of heterocycles. 

Cascade heterocyclization in synthesis of thiophene derivatives and their fused analogs 05RKZ(6)11. 

The main application of mercury derivatives has been to the synthesis of heterocyclic arsenicals. Thus diphenylene oxide-1-arsonic acid and pyridyl-3-arsonic acid have been isolated following oxidation of the initial reaction products obtained from arsenic trichloride and the appropriate heterocyclic mercury chloride 114,115). Furan and thiophene derivatives have been similarly prepared 116,117,118). 

Mullins, R. J. Williams, D. R. Hinsberg Synthesis of Thiophene Derivatives. InName Reactions in Heterocyclic Chemistry, Li, J. J., Corey, E. J., Eds. Wiley Sons Hoboken, NJ, 2005, pp 199-206. (Review). 

Rivas, C., Pacheco, D., Vargas, R, and Ascanio, J., Synthesis of oxetanes by photoaddition of carbonyl compounds to thiophene derivatives,/. Heterocyclic Chem., 18,1065,1981. 

Representative of recent applications of the reaction to the synthesis of heterocycles are the photodehydrochlorination of chlorobenzo[b]thiophen (347) to give the fused pyrimidone 348,287 the photoelimination of HI from iodobenzene derivatives 349 to give the benzazepines 350,288 and the synthesis of the medium ring aza-heterocycle 351 by irradiation of the chloro precursor 352.289 Included among the many other examples of... 

The synthesis of methylimidazole-thiophene compounds was reported by Santos et al. [46] and has been included for completeness, although no biological activity has been reported for these heterocycles. The formation of these imidizole-thiophenes (24a-d), occurs via the condensation of 2-formylthiophene (25) with benzil derivatives (26a-d) in the presence of ammonium acetate to yield the imidazole-thiophene compounds (27a-d). These compounds can then be N-methylated by treatment with iodomethane in... 

Oximes and their derivatives are widely used in organic synthesis. A number of reviews are devoted to the chemistry and biological activity of oximes and their derivatives The synthesis, reactions and biological activity of oximes containing a heterocyclic substituent, e.g. furan and thiophene", indole and isatin, pyridine, pyrrole, quinoline and five-membered heterocycles with two heteroatoms have been reviewed. 

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