Solvent‐Free Synthesis of Heterocyclic Compounds Using Microwaves

Microwave-enhanced solvent-free synthetic approach is described that features simplicity, manipulative ease of the operation and conservation of solvents as the main advantages. This eco-friendly approach, which has found application in facile organic functional group transformations, is applied to rapid assembly of heterocyclic compounds. A variety of solid state reactions are described that occur rapidly at ambient pressure under solventless conditions and provide ready access to intermediates such as enamines and α-tosyloxyketones which can be transformed in situ to biologically significant heterocyclic compounds such as isoflav-3-enes, flavones, quinolones, 2-aroylbenzo[b]furans and thiazoles in one-pot operation. Multicomponent reactions under these solvent-free conditions can be adapted for high speed parallel synthesis and are exemplified by assembly of dihydropyrimidine-2(1H)-ones (Biginelli reaction) and imidazo[1,2-a]annulated pyridines, pyrazines and pyrimidines (Ugi reaction) which may have potential in building a library of such compounds.

[1]  H. Meshram,et al.  Selective oxidation of sulfides to sulfoxides and sulfones by microwave thermolysis on wet silica-supported sodium periodate , 1997 .

[2]  T. Grese,et al.  NOVEL METHODOLOGY FOR THE SYNTHESIS OF ESTROGENIC AND ANTIESTROGENIC ISOFLAV-3-ENES , 1995 .

[3]  S. P. Fodor,et al.  Applications of combinatorial technologies to drug discovery. 1. Background and peptide combinatorial libraries. , 1994, Journal of medicinal chemistry.

[4]  Rajender S. Varma,et al.  Microwave-Assisted High-Speed Parallel Synthesis of 4-Aryl-3,4-dihydropyrimidin-2(1H)-ones using a Solventless Biginelli Condensation Protocol , 1999 .

[5]  R. Varma,et al.  Microwave-accelerated three-component condensation reaction on clay: solvent-free synthesis of imidazo[1,2-a] annulated pyridines, pyrazines and pyrimidines , 1999 .

[6]  B. Banik,et al.  MORE Chemistry in a Microwave , 1997 .

[7]  R. Varma,et al.  Wet alumina supported chromium(VI) oxide: Selective oxidation of alcohols in solventless system , 1998 .

[8]  R. Varma.  Solvent-free organic syntheses on mineral supports using microwave irradiation , 1999 .

[9]  W. Spitzer,et al.  Imidazo[1,2-a]pyrimidines and imidazo[1,2-a]pyrazines: the role of nitrogen position in inotropic activity. , 1988, Journal of medicinal chemistry.

[10]  R. Gedye,et al.  The use of microwave ovens for rapid organic synthesis , 1986 .

[11]  L. C. King,et al.  The Reaction of Ketones with Iodine and Thiourea1 , 1950 .

[12]  A. Hantzsch.  Untersuchungen über Azole , 1889 .

[13]  S. Caddick,et al.  Microwave assisted organic reactions , 1995 .

[14]  R. Varma,et al.  SOLID STATE DETHIOACETALIZATION USING CLAYFEN , 1997 .

[15]  Alain Petit,et al.  NEW SOLVENT-FREE ORGANIC SYNTHESIS USING FOCUSED MICROWAVES , 1998 .

[16]  B. S. Setty,et al.  Seco-oestradiols and some non-steroidal oestrogens: structural correlates of oestrogenic action. , 1979, Journal of steroid biochemistry.

[17]  J. Bazureau,et al.  A new route to 2-oxazolines, bis-oxazolines, and 2-imidazoline-5-ones from imidates using solvent-free cycloadditions: Synthesis, chemical properties, and PM3 MO calculations , 1997 .

[18]  W. Lawson.  Œstrogenic activity of some derivatives of isoflaven and isoflavanol , 1954 .

[19]  T. A. Geissman,et al.  The Rearrangement of 2-Acetyl- and 2-Benzoylcoumarone Oxime p-Toluenesulfonates , 1955 .

[20]  Tomas Hudlicky,et al.  Design Constraints in Practical Syntheses of Complex Molecules: Current Status, Case Studies with Carbohydrates and Alkaloids, and Future Perspectives. , 1996, Chemical reviews.

[21]  R. Varma,et al.  Copper(II) nitrate on clay (claycop)-hydrogen peroxide: Selective and solvent-free oxidations using microwaves , 1998 .

[22]  R. Varma,et al.  Solid state regeneration of ketones from oximes on wet silica supported sodium periodate using microwaves , 1997 .

[23]  R. Varma,et al.  Microwave-assisted Henry reaction: Solventless synthesis of conjugated nitroalkenes , 1997 .

[24]  R. Varma,et al.  Microwave-accelerated crossed Cannizzaro reaction using barium hydroxide under solvent-free conditions , 1998 .

[25]  A. Loupy,et al.  Selective Dealkylations of Alkyl Aryl Ethers in Heterogeneous Basic Media under Microwave Irradiation. , 1997 .

[26]  E. Bickoff,et al.  COUMESTROL, PLANT PHENOLICS, AND SYNTHETIC ESTROGENS: A CORRELATION OF STRUCTURE AND ACTIVITY. , 1962, Journal of medicinal and pharmaceutical chemistry.

[27]  H. Meshram,et al.  SOLID STATE CLEAVAGE OF SEMICARBAZONES AND PHENYLHYDRAZONES WITH AMMONIUM PERSULFATE-CLAY USING MICROWAVE OR ULTRASONIC IRRADIATION , 1997 .

[28]  I. Ugi,et al.  Multicomponent reactions in organic chemistry , 1994 .

[29]  R. Varma,et al.  Solid state oxidation of 1,4-dihydropyridines to pyridines using phenyliodine(III) bis(trifluoroacetate) or elemental sulfur , 1999 .

[30]  Rajender S. Varma,et al.  Microwave-Assisted Facile Synthesis of Imines and Enamines using Envirocat EPZGR as a Catalyst , 1997 .

[31]  R. Varma,et al.  Microwave-assisted deacetylation on alumina: a simple deprotection method , 1993 .

[32]  R. Varma,et al.  Active manganese dioxide on silica: Oxidation of alcohols under solvent-free conditions using microwaves☆ , 1997 .

[33]  R. Varma,et al.  Microwave-accelerated solvent-free synthesis of thioketones, thiolactones, thioamides, thionoesters, and thioflavonoids. , 1999, Organic letters.

[34]  R. Varma,et al.  Clay catalyzed synthesis of imines and enamines under solvent-free conditions using microwave irradiation , 1997 .

[35]  L. Weber,et al.  Synthesis of Imidazo[1,2-a] annulated Pyridines, Pyrazines and Pyrimidines by a Novel Three-Component Condensation , 1998 .

[36]  R. Varma.  Dietary bioflavonoids, chalcones, and related alkenones in prevention and treatment of cancer. , 1996, Nutrition.

[37]  S. P. Fodor,et al.  Applications of combinatorial technologies to drug discovery. 2. Combinatorial organic synthesis, library screening strategies, and future directions. , 1994, Journal of medicinal chemistry.

[38]  R. Varma,et al.  Sodium borohydride on wet clay: Solvent-free reductive amination of carbonyl compounds using microwaves☆ , 1998 .

[39]  S. Antus,et al.  Reaction of chalcones with NBS, a simple one pot synthesis of 2-aroylbenzo[b]furanes , 1996 .

[40]  R. Varma,et al.  Microwave-assisted oxidation of alcohols under solvent-free conditions using clayfen , 1997 .

[41]  J. A. Donnelly,et al.  The chemistry of 2'-amino analogs of 2'-hydroxychalcone and its derivatives , 1990 .

[42]  G. Kabalka,et al.  Organic reactions on alumina , 1997 .

[43]  D. Villemin,et al.  Dry Reaction Under Microwave: Condensation of Sulfones with Aldehydes on KF-Alumina , 1991 .

[44]  R. Varma,et al.  An Expeditious Synthesis of Flavones on Montmorillonite K 10 Clay with Microwaves , 1998 .

[45]  R. Varma,et al.  Growth inhibitory effects of bioflavonoids and related compounds on human leukemic CEM-C1 and CEM-C7 cells. , 1992, Cancer Letters.

[46]  R. Varma,et al.  Solid state synthesis of 2-aroylbenzo[b]furans, 1,3-thiazoles and 3-aryl-5,6-dihydroimidazo[2,1-b][1,3]thiazoles from α-tosyloxyketones using microwave irradiation† , 1998 .

[47]  R. Dahiya,et al.  An Expeditious and Solvent-Free Synthesis of 2-Amino-Substituted Isoflav-3-enes Using Microwave Irradiation† , 1998 .

[48]  Jonathan S. Dordick,et al.  MICROWAVE ASSISTED COMBINATORIAL CHEMISTRY SYNTHESIS OF SUBSTITUTED PYRIDINES , 1998 .

[49]  R. Varma,et al.  Microwave-assisted reduction of carbonyl compounds in solid state using sodium borohydride supported on alumina , 1997 .