Oxidation of 2-(thiazol-2-yl)acrylonitrile derivatives with an H<Subscript>2</Subscript>O<Subscript>2</Subscript>—KOH system: Convenient route to new oxirane-2-carboxamides

An efficient procedure was developed for the synthesis of previously unknown 3-aryl(styryl)-2-(4-arylthiazol-2-yl)oxirane-2-carboxamides and 2-(4-arylthiazol-2-yl)-1-oxaspiro[2.5]octane-2-carboxamides based on treatment of (E)-3-aryl-2-(4-arylthiazol-2-yl)acrylonitriles and cyclohexylidene(4-arylthiazol-2-yl)acetonitriles with an H₂O₂—KOH system in EtOH. Oxidation of (E)-3-(4-chlorophenyl)-2-(4-phenylthiazol-2-yl)acrylonitrile with an H₂O₂—AcOH system affords 3-(4-chlorophenyl)-2-(4-phenylthiazol-2-yl)oxirane-2-carbonitrile in 55% yield. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2319–2322, October, 2005.     

A new stereoselective synthesis of 2-amino-4,5-dihydrothiophene-3-carbonitrile derivatives

A new stereoselective method for the synthesis of trans-isomers of 2-amino-4-aryl-5-benzoyl-4,5-dihydrothiophene-3-carbonitriles was proposed. The method involves base-catalyzed reactions of phenacyl thiocyanate with 3-(het)aryl-2-cyanoprop-2-enethioamides. (4R,5S/4S,5R)-2-Amino-5-benzoyl-4-(2-chlorophenyl)-4,5-ihydrothiophene-3-carbonitrile was structurally characterized by X-ray diffraction analysis. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1379–1383, July, 2007.     

Synthesis of 3-(4-chlorophenyl)oxirane-2,2-dicarboxamide

Oxidation of (E)-3-(4-chlorophenyl)-2-cyanoprop-2-enethioamide with hydrogen peroxide or the H₂O₂-KOH system gave 3-(4-chlorophenyl)oxirane-2,2-dicarboxamide. This compound was also obtained by an independent “one pot” synthesis from p-chlorobenzaldehyde and 2-cyanoacetamide through in situ oxidation of their adduct (E)-3-(4-chlorophenyl)-2-cyanoprop-2-eneamide with the H₂O₂-KOH system. The structure of 3-(4-chlorophenyl)oxirane-2,2-dicarboxamide was confirmed by X-ray diffraction and spectroscopic data. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1417–1419, July, 2007.     

Regioselective reduction of 2-cyanoprop-2-enethioamides with sodium borohydride

Treatment of 2-cyanoprop-2-enethioamides with NaBH₄ in EtOH gave C-alkylated cyanothioacetamides in 62–69% yields.     

A Convenient Mannich-Type One-Pot Synthesis of Pyrimido[6,1-b][1,3,5]thiadiazines

3-(Het)aryl-2-cyanoprop-2-enethioamides easily reacted with primary amines and excessive formaldehyde under mild conditions to afford pyrimido[6,1-b][1,3,5]thiadiazine derivatives in moderate yields. Furthermore, 2-cyano-2-cyclohexylideneethanethioamide reacted in the similar Mannich-type manner to give spiro-conjugated pyrimido-1,3,5-thiadiazines. The structure of 3,7-dibenzyl-8-(fur-2-yl)-3,4,7,8-tetrahydro-2H,6H-pyrimido[6,1-b][1,3,5]thiadiazine-9-carbonitrile was determined by X-ray diffraction analysis.     

A Convenient Mannich-Type One-Pot Synthesis of Pyrimido[6,1-b][1,3,5]thiadiazines

Summary. 3-(Het)aryl-2-cyanoprop-2-enethioamides easily reacted with primary amines and excessive formaldehyde under mild conditions to afford pyrimido[6,1-b][1,3,5]thiadiazine derivatives in moderate yields. Furthermore, 2-cyano-2-cyclohexylideneethanethioamide reacted in the similar Mannich-type manner to give spiro-conjugated pyrimido-1,3,5-thiadiazines. The structure of 3,7-dibenzyl-8-(fur-2-yl)-3,4,7,8-tetrahydro-2H,6H-pyrimido[6,1-b][1,3,5]thiadiazine-9-carbonitrile was determined by X-ray diffraction analysis.     

Reaction of the zinc enolate derived from 1,1-dibromo-3,3-dimethylbutan-2-one with 3-aryl-2-cyanopropenoic acid amides and esters and 2-oxochromene-3-carboxamides

Zinc enolate derived from 1,1-dibromo-3,3-dimethylbutan-2-one reacts with 3-aryl-2-cyanoprop-2-enamides and aryl 3-aryl-2-cyanoprop-2-enoates to give the corresponding derivatives of 3-aryl-2-(2,2-dimethylpropanoyl)-1-cyanocyclopropane-1-carboxylic acid as a single stereoisomer with cis arrangement of the hydrogen atoms at the cyclopropane ring. The reactions of the same zinc enolate with 3-morpholinocarbonyl-2H-chromen-2-one and 2-morpholinocarbonyl-3H-benzo[f]chromen-3-one lead to formation of 1-(2,2-dimethylpropanoyl)-1a-morpholinocarbonyl-1a,7b-dihydrocyclopropa[c]chromen-2-one and 1-(2,2-dimethylpropanoyl)-1a-morpholinocarbonyl-1a,9c-dihydrobenzo[f]cyclopropa[c]chromen-2-one, respectively as a single stereoisomer.     

Transformations of 5-(2-arylethynyl)-2-methyl-2H-tetrazoles under superelectrophilic activation

Reaction of 5-arylethynyl-2-methyl-2H-tetrazoles (acetylene tetrazoles) with arenes under the action of Brønsted superacid CF₃SO₃H or acidic zeolite HUSY CBV-720 gives rise to E-/Z-5-(2,2-diarylethenyl)-2-methyl-2H-tetrazoles, as products of hydroarylation of acetylene bond, in yields up to 98% with predominant formation of E-isomers. Cationic intermediates of these reactions have been studied theoretically by DFT calculations. Addition of CF₃SO₃H to the triple bond of acetylene tetrazoles leads to the corresponding E-/Z-vinyl triflates in high yields. Hydration of triple bond in these tetrazoles in H₂SO₄ results in the formation of 5-(2-aryl-2-oxoethyl)-2-methyl-2H-tetrazoles. Tandem hydroarylation-ionic hydrogenation of acetylene tetrazoles in the systems acid(CF₃SO₃H or AlCl₃)-arene-cyclohexane affords 5-(2,2-diarylethyl)-2-methyl-2H-tetrazoles.     

Triphenylphosphine as an effective catalyst for ketoximes addition to acylacetylenes: regio- and stereospecific synthesis of (E)-(O)-2-(acyl)vinylketoximes

Triphenylphosphine catalyzes the regio- and stereospecific addition of ketoximes to acylacetylenes, whereas classical conditions using acetylene (KOH/DMSO, 70 °C) are unsuitable for this purpose. The reaction proceeds under mild conditions (CH₂Cl₂, rt, 7 h) to afford (E)-(O)-2-(acyl)vinylketoximes (92-98% stereoselectivity) in a yield of up to 85%. The (E)-adducts obtained are energetically less favorable than the corresponding (Z)-isomers and are gradually enriched with (Z)-isomers, thus indicating the kinetic control of (E)-stereoselectivity of the reaction.     

Stereoselective alkenylation of a 1,3-disubstituted pyrazol-5-one through ring transformation of 2H-pyran-2-ones

A one-pot stereoselective alkenylation of 1-(3-chlorophenyl)-3-methyl-1,4-dihydro-5-pyrazolone 2 by 2H-pyran-2-ones 1 to give (E,E)-5-aryl-5-[1-(3-chlorophenyl)-3-methyl-5-oxo-1,5-dihydropyrazol-4- ylidene]-3-methylsulfanyl-pent-3-en-carbonitrile/methyl carboxylate 3 has been delineated through ring transformation in moderate yields.     

Iodine-catalyzed synthesis of 2-arylpyrazolo[5,1-b]quinazolin-9(3H)-one derivatives in ionic liquids via domino reaction

The domino reaction of (E)-2-amino-N′-(1-arylethylidene)benzohydrazide and triethyl orthoformate in ionic liquids catalyzed by 10 mol % iodine gave 3a,4-dihydro-2-arylpyrazolo[5,1-b]quinazolin-9(3H)-one derivatives unexpectedly. In the presence of K₂S₂O₈, it could be oxidized to aromatized products in good yields.     

Bismuth triflate-catalyzed rearrangement of acetates of the Baylis-Hillman adducts into (E)-trisubstituted alkenes

In the presence of a catalytic amount of bismuth triflate, methyl 3-acetoxy-3-aryl-2-methylenepropanoates and 3-acetoxy-3-aryl-2-methylenepropanitriles were smoothly converted into methyl (2E)-2-(acetoxymethyl)-3-arylprop-2-enoates and (2E)-2-(acetoxymethyl)-3-arylprop-2-enenitriles, respectively. A remarkable reversal in stereochemical directions from ester to nitrile was observed. 3-Aryl-3-hydroxy-2-methylenepropanoates and 3-aryl-3-hydroxy-2-methylenepropanitriles could be easily obtained as Baylis-Hillman adducts from methyl acrylate and acrylonitrile, respectively. The overall process is an efficient isomerization of the Baylis-Hillman adducts to the corresponding cinnamyl derivatives. The isomerization reaction proceeded rapidly and afforded smoothly the cinnamyl acetates in moderate to very good yields using catalytic amounts of Bi(OTf)₃·4H₂O (10 mol %).     

Alumina supported-CeCl3·7H2O-NaI: an efficient catalyst for the cyclization of 2′-aminochalcones to the corresponding 2-aryl-2,3-dihydroquinolin-4(1H)-ones under solvent free conditions

We recently advanced silica gel supported-TaBr₅ as an efficient catalyst for the isomerization of 2′-aminochalcones to the corresponding 2-aryl-2,3-dihydroquinolin-4(1H)-ones under solvent free conditions (Tetrahedron Lett. 2006, 47, 2725-2729). This conversion can be further improved through the use of more economic alumina supported-CeCl₃·7H₂O-NaI, providing high yields of up to 98% at lower reaction temperatures. This stable catalyst is easily prepared, active under solvent-free conditions and employed under environmentally friendly conditions.     

Cyclopropanation of 2-arylmethylidenemalononitriles,alkyl 3-aryl-2-cyanoprop-2-enoates,and N-substituted 3-aryl-2-cyanoprop-2-enamides with bromine-containing zinc enolates

Zinc enolates derived from 2,2-dibromoindan-1-one and 2,2-dibromo-1,2,3,4-tetrahydronaphthalen-1-one reacted with 2-arylmethylidenemalononitriles, alkyl 3-aryl-2-cyanoprop-2-enoates, and N-substituted 3-aryl-2-cyanoprop-2-enamides to give, respectively, 3-aryl-1′-oxo-1′,3′-dihydrospiro[cyclopropane-1,2′-indene]-2-2-dicarbonitriles, 3-aryl-1′-oxo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalene]-2,2-dicarbonitriles, alkyl 3-aryl-2-cyano-1′-oxo-1′,3′-dihydrospiro[cyclopropane-1,2′-indene]-2-carboxylates, alkyl 3-aryl-2-cyano-1′-oxo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalene]-2-carboxylates, and N-substituted 3-aryl-2-cyanol-1′-oxo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalene]-2-carboxamides as a single diastereoisomer. The stereoconfiguration of the products was determined by ¹H and ¹³C NMR spectroscopy.     

Sodium dithionite initiated addition of CF2Br2, CF3I and (CF3)2CFI to allylaromatics: Synthesis and the reactivity of 4-aryl-1,1-difluorodienes and 4-aryl-1,1-bis(trifluoromethyl)dienes

Sodium dithionite initiated addition of CF₂Br₂, CF₃I and (CF₃)₂CFI to the terminal double bond of allylbenzenes and of (CF₃)₂CFI to allylpyridines in a MeCN/H₂O system were investigated. The reactions of CF₂Br₂ with allylbenzenes gave comparable amounts of adducts, 1-(2,4-dibromo-4,4-difluorobutyl)benzenes, debrominated products,1-(4-bromo-4,4-difluorobutyl)benzenes, and dimeric compounds in total yields 40-66%. Treatment of the adducts with DBU resulted in double dehydrohalogenation affording 4-aryl-1,1-difluorobutadienes which undergo Diels-Alder condensation with nitrogen dienophiles to give N-heterocycles with difluoromethylene group in the ring. The reactions of CF₃I and (CF₃)₂CFI with allylbenzenes gave the respective adducts, (4,4,4-trifluoro-2-iodobutyl)benzenes and 1-(4,5,5,5-tetrafluoro-4-(trifluoromethyl)-2-iodopentyl)benzenes as the main products. Dehydrohalogenation of these adducts resulted, respectively, in (4,4,4-trifluoro-but-1-enyl)benzenes and 4-aryl-1,1-bis(trifluoromethyl)butadienes in high yields. (CF₃)₂CFI reacted rapidly with allylpyridines to give mixtures from which, after treatment with DBU, 4-pyridyl-1,1-bis(trifluoromethyl)butadienes were isolated in a ca. 60% yield.     

Interaction of decacarbonyldimanganese and decacarbonyldirhenium with 1-aryl-3-cyanoprop-2-en-1-ones

The reactions of M₂(CO)₁₀ (M = Mn, Re) withtrans-1-aryl-3-cyanoprop-2-en-1-ones in the presence of Me₃NO proceed with replacement of the CO ligand and lead to complexeseq-(1-aryl-3-cyanoprop-2-en-1-on)nonacarbonyldimanganese andeq-(1-aryl-3-cyanoprop-2-en-1-on)nonacarbonyldirhenium complexes where the metals are bonded with the ligand through the nitrogen atom of the cyanogroup. The treatment of (1-phenyl-3-cyanoprop-2-en-1-on)nonacarbonyldirhenium with a second equivalent of the ligand resulted in the disubstituted complex,eq,eq-bis(1-phenyl-3-cyanoprop-2-en-1-on)octacarbonyldirhenium in a good yield. The structures of the obtained complexes are discussed on the basis of¹³C,¹H NMR, and IR-spectroscopy.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1485–1487, August, 1994.This work was supported in part by the Russian Foundation for Basic Research (grant No 93-03-4028).     

An efficient synthesis of highly substituted pyrroles from β-oxodithiocarboxylates

α-Oxoketene-N,S-acetals, prepared by the reaction of alkyl glycinate hydrochlorides with β-oxodithiocarboxylates followed by alkylation, underwent cyclization in presence of chloromethyleneiminium salt derived from POCl₃/DMF to afford alkyl-3-aryl-4-formyl-5-(alkylsulfanyl)-1H-pyrrole-2-carboxylates in excellent yields. Alkyl-3-aryl-5-(alkylsulfanyl)-1H-pyrrole-2-carboxylates were formed in moderate yields when the same N,S-acetals were treated with DBU.     

An efficient approach for the synthesis of N-Phenylcarboxamido-2-aryl-1,2-dihydro-(4H)-3,1-benzoxazine-4-ones

An efficient synthesis of N-phenylcarboxamodo-2-aryl-1,2-dihydro-(4H)-3,1-benzoxazin-4-ones is described by cyclization reaction of some 2-(benzylidene-amino)-benzoic acids with phenyl isocyanate under reflux conditions in CHCl₃. Higher yields of the products were produced in high purity with simple work-up.     

Chemistry of iminofuran: VIII. Recyclization of 5-aryl-3-arylimino-3H-furan-2-ones effected by cyanoacetic acid derivatives

The recyclization of 5-aryl-3-arylimino-3H-furan-2-ones under the action of esters, nitriles, and amides of cycnoacetic acids resulted in the corresponding esters, nitriles, and amides of (5E)-2-amino-1-aryl-4-oxo-5-(2-oxoethylidene)-1H-4,5-dihydropyrrole-3-carboxylic acids.     

Reaction of 2-methylquinoline with 3-phenylprop-2-ynenitrile in the KOH—H<Subscript>2</Subscript>O system

The reaction of 2-methylquinoline with 3-phenylprop-2-ynenitrile in the presence of water (0—25 °C, 20 mol.% KOH, 5 equiv. H₂O) is accompanied by the loss of aromaticity of the quinoline nucleus and results in double functionalization of the molecule at the nitrogen atom and the methyl group. Two 2-cyano-1-phenylethenyl groups were introduced into the molecule to form (2E,4E)-4-{1-[(Z)-2-cyano-1-phenylethenyl]quinolin-2(1H)-ylidene}-3-phenylbut-2-enenitrile in 59—67% yield. This reaction is stereoselective: the N-2-cyano-1-phenylethenyl-substituent has the Z-configuration, while the 1,3-diene moiety at the methyl group has the E,E-configuration. (2E)-3-Phenyl-4-(quinolin-2-yl)but-2-enenitrile that formed as a by-product (0—24% yields) is formally the addition product of the methyl group of the quinoline substrate at the acetylenic bond.