Derivatives of 2-oxo-3(2H)-benzothiazolineacetonitrile and related compounds. I. Synthesis of N-hydroxy-2-oxo or thioxo-3(2H)-benzothiazolineethanimidamide and related products

The following methods afforded the titled acetonitriles 1–5 in excellent yields: (1) the reaction of the appropriate 2-benzothiazolinones with chloroacetonitrile under basic conditions and (2) the dehydration of the appropriate 2-oxo-3(2H)-benzothiazolineacetamides with phosphorus oxychloride or pentoxide. The reaction of the acetonitriles 1–5 and 2-thioxo-3(2H)-benzothiazolmeacetonitrile with hydroxylamine afforded the titled compounds 6–11 . Supporting nmr and mass spectral data are discussed.     

1,3-Dipolar cycloadditions of mesitonitrile oxide with (9-fluorenylidene)-aceto- and malono-nitriles. Synthesis of mono- and bis-1,2,4-oxadiazolylmethane derivatives

Mesitonitrile oxide reacts with C ≡ N bond of (aryl)(9-fluorenylidene)acetonitriles 1 forming in very good yields the corresponding 1,2,4-oxadiazoles 2. Analogously also proceeds the reaction of mesitonitrile oxide with 9-fluorenylidenemalonodinitrile (3) with the formation of bis-1,2,4-oxadiazole derivative 4.     

2-Oxobenzo[h]chromene: a novel entry for the synthesis of functionalized angular polycyclic azaarenes

An efficient and short synthesis of (5,6-dihydrobenzo[h]pyrido[2,1-b]quinazolin-2-ylidene)acetonitriles, (5,6-dihydrobenzo[h]pyrazino[2,1-b]quinazolin-2-ylidene)acetonitriles and (5,6-dihydrobenzimidazo[1,2-b]benzo[f]isoquinolin-7-yl)acetonitriles in good yields is delineated through base catalyzed ring transformation of 4-(piperidin-1-yl)-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles with 2-amino-pyridine, 2-aminopyrazine and (imidazo-2-yl)acetonitrile.     

Novel Selected Tandem Transformations of the Amino and Carbonyl/Nitrile Groups in the Gewald Thiophenes

Novel transformations of the amino and carbonyl/nitrile groups in the Gewald thiophenes were studied for thienopyrimidine synthesis. It was found that 2-amino-thiophene-3-carboxamides and ethyl 2-(acetylamino)-4,5,6,7-tetrahydro-1-benzothiophene-3-carbo- xylate did not yield tetrazole derivatives, neither in the reaction with triethyl orthoformate and sodium azide, nor in the reaction with phosphorus oxychloride and sodium azide, correspondingly. On the contrary, derivatives of thieno[2,3-d]pyrimidin-4(3H)-one and thieno[2,3-d][1,3]oxazin-4-one were isolated. New 2-azidothiophenes [2-azido-4,5,6,7-tetra hydro-1-benzothiophene-3-carbonitrile and 2-azido-4,5,6,7-tetrahydro-1-benzothiophen-3-yl(phenyl)methanone] were synthesized and used in anionic domino reactions with activated acetonitriles to yield thieno[3,2-e][1,2,3]triazolo[1,5-a]pyrimidines and/or 2-(5-amino-1H-1,2,3-triazol-1-yl)thiophenes. Finally, a new ring system of thieno[3,2-e]pyrazolo[1,5-a]pyrimidine was synthesized via a domino reaction of ethyl 2-[(2Z)-2-(1-chloro-2-ethoxy-2-oxoethylidene)hydrazino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate with activated acetonitriles.     

Facile synthesis and characterization of novel benzo-fused macrocyclic dicarbonitriles and pyrazolo-fused macrocycles containing thiazole subunits

Abstract

Novel bis[2-(thiazol-2-yl)acetonitriles], linked to aliphatic cores via ethers, were prepared by the reaction of the appropriate bis(2-bromoethan-1-one) with 2-cyanothioacetamide in dioxane at reflux. Bis[2-(thiazol-2-yl)acetonitriles] were taken as key intermediates for the preparation of a new class of macrocyclic dicarbonitriles bearing two thiazole units and containing two O₂-donor sets and fused with two benzene units. The target macrocyclic dicarbonitriles were prepared by the cyclocondensation of bis[2-(thiazol-2-yl)acetonitriles] with the appropriate bis(aldehydes) in N,N-dimethylformamide in the presence of piperidine at reflux. Moreover, a new class of pyrazolo-fused macrocycles containing thiazole subunits were prepared by the reaction of macrocyclic dicarbonitriles with hydrazine hydrate in ethanol at reflux. The structures of the novel macrocycles bearing thiazole subunits were elucidated by considering their elemental analyses as well as their IR, mass, ¹H NMR and ¹³C NMR spectral data.     

Hydroxypropyl substituted nitrogen bridgehead fused cyanopyridines

The reaction of 2-hetaryl-2-(tetrahydro-2-furanyliden)acetonitriles with substituted acetonitriles as C-nucleophiles has been investigated and the mechanism of the reaction has been suggested. A base promoted Michael addition of the substituted acetonitriles to 2-hetaryl-2-(tetrahydro-2-furanyliden)acetonitriles followed by ring transformations has provided novel convenient synthetic methods to nitrogen bridgehead fused cyanopyridines bearing hydroxypropyl side chain. The structures of obtained compounds have been established based on NMR spectroscopy investigation and X-ray diffraction data.     

Synthesis of Pyrrolo[2,1-b]thiazol-3-one Derivatives

Ethyl [4-oxo-3-(2-oxo-2-arylethyl)thiazolidin-2-ylidene]acetates and [4-oxo-3-(2-oxo-2-arylethyl)thiazolidin-2-ylidene]acetonitriles were shown to react with substituted benzaldehydes at the endocyclic methylene group leading to the corresponding 5-arylmethylidene derivatives. Their treatment with DMF · POCl₃ complex yielded 3-oxo-5-aroyl-2-arylmethylidene-2,3-dihydropyrrolo[2,1-b]thiazole-7-carboxylic acids ethyl esters and -7-carbonitriles. The structures of the pyrrolothiazoles were confirmed by an X-ray crystallographic study, which indicated the (Z)-configuration at the arylmethylidene moiety.     

One step synthesis of 6,7-dimethyl-2-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a][1,3]pyrimidines

A one-step synthesis of substituted pyrrolo[1,2-a][1,3]pyrimidines from acetyl methyl carbinol, 3-aminopropionic acid, and substituted acetonitriles is reported.     

Synthesis and Properties of 6,7,8-Substituted 2-(4-Oxo-3,4-dihydro-2-quinazolinyl)acetonitriles

2-(4-Oxo-3,4-dihydro-2-quinazolinyl)acetonitriles have been obtained by the interaction of -cyanoethylthioiminoacetate with substituted anthranilic acids. Prototropy became apparent in the series of synthesized compounds. Reactions of the 2-(4-oxo-3,4-dihydro-2-quinazolinyl)acetonitriles have been carried out with (hetero)aromatic aldehydes leading to the formation of 3-aryl-2-(4-oxo-3,4-dihydro-2-quinazolinyl)acrylonitriles.     

Facile Synthesis of Aryl‐Pyridyl,Pyridazinyl, Pyrazinyl,and Triazinyl Acetonitriles

Dihalo pyridine, pyrazine, and pyridazine analogues were converted to the corresponding monohalo acetonitrile analogues through nucleophilic displacement of the halogen with the anion of tert‐butyl cyanoacetate. The monohalo acetonitriles reacted under Suzuki or Stille conditions to form the title compounds.     

Bis-Cyclometalated Indazole Chiral-at-Rhodium Catalyst for Asymmetric Photoredox Cyanoalkylations

A new class of bis-cyclometalated rhodium(III) catalysts containing two inert cyclometalated 6-tert-butyl-2-phenyl-2H-indazole ligands and two labile acetonitriles is introduced. Single enantiomers (>99 % ee) were obtained through a chiral-auxiliary-mediated approach using a monofluorinated salicyloxazoline. The new chiral-at-metal complex is capable of catalyzing the visible-light-induced enantioselective α-cyanoalkylation of 2-acyl imidazoles in which it serves a dual function as the chiral Lewis acid catalyst for the asymmetric radical chemistry and at the same time as the photoredox catalyst for the visible-light-induced redox chemistry (up to 80 % yield, 4:1 d.r., and 95 % ee, 12 examples).     

Synthesis of Pyrrolo[2,1-<Emphasis Type="Italic">b</Emphasis>]thiazol-3-one Derivatives

Summary. Ethyl [4-oxo-3-(2-oxo-2-arylethyl)thiazolidin-2-ylidene]acetates and [4-oxo-3-(2-oxo-2-arylethyl)thiazolidin-2-ylidene]acetonitriles were shown to react with substituted benzaldehydes at the endocyclic methylene group leading to the corresponding 5-arylmethylidene derivatives. Their treatment with DMF · POCl₃ complex yielded 3-oxo-5-aroyl-2-arylmethylidene-2,3-dihydropyrrolo[2,1-b]thiazole-7-carboxylic acids ethyl esters and -7-carbonitriles. The structures of the pyrrolothiazoles were confirmed by an X-ray crystallographic study, which indicated the (Z)-configuration at the arylmethylidene moiety.     

An efficient synthesis of (E)-(2-arylpyrazino[1,2-a]pyrimidine-4-ylidene)acetonitriles and cyanomethyl appended pyrimidines

A series of (E)-(2-arylpyrazino[1,2-a]pyrimidine-4-ylidene)acetonitriles 5a-j and aryl/heteroaryl tethered pyrimidin-4-yl acetonitriles 6a-e has been synthesized in excellent yields through base catalyzed ring transformation of suitably functionalized 2H-pyran-2-ones 3 using 2-aminopyrazine 4a and arylamidinium salts 4b, separately.     

Five-membered 2,3-dioxoheterocycles: LXXIX. Three-component condensation of 1<Emphasis Type="Italic">H</Emphasis>-pyrrol-2,3-diones with acetonitriles and dimedone. Crystal and molecular structure of substituted spiro[chromene-4,3′-pyrrole]

5-Phenyl-4-ethoxycarbonyl-1H-pyrrole-2,3-diones react with acetonitriles and dimedone to form ethyl 2-amino-7,7-dimethyl-2′,5-dioxo-5′-phenyl-1′,2′,5,6,7,8-hexahydrospiro[chromene-4,3′-pyrrole]-4′-carboxylates. The crystal and molecular structure of ethyl 2-amino-1′-benzyl-7,7-dimethyl-2′,5-dioxo-5′-phenyl-3-cyano-1′,2′,5,6,7,8-hexahydrospiro[chromene-4,3′-pyrrole]-4′-carboxylate was proved by XRD analysis.     

A new dimerization reaction producing 2‐amino‐9‐oxopyrrolo‐[2,1‐b]quinazoline‐1‐carbonitriles and analogous pyrrolo‐[1,2‐a]thieno[3,2‐d] pyrimidinecar bonitriles

A series of 2‐alkylthio‐4‐oxo‐3‐quinazolineacetonitriles 4 and 2‐alkylthio‐4‐oxothieno[3,2‐d]pyrimidine‐3‐acetonitriles 8 was prepared. Upon treatment with sodium hydride, compounds 4 and 8 react to give 2‐amino‐4,9‐dihydro‐9‐oxopyrrolo[2,1‐b]quinazoline‐1‐carbonitriles 9 and 6‐amino‐4,9‐dihydro‐9‐oxopyrrolo[1,2‐a]thieno[3,2‐d]pyrimidine‐7‐carbonitriles 10 , respectively. The transformation of compounds 4 and 8 to the tricyclic aminonitriles 9 and 10 involves a dimerization step followed by a pyrrole cyclization. The tert‐butyl ester derivatives 4d and 8d upon treatment with sodium hydride underwent a Thorpe‐Ziegler cyclization to provide enaminoesters of fused 1,3‐thiazines ( 16 and 17 , respectively) as major products.     

Cyanation of halo derivatives by acetone cyanohydrin

A preparative method is proposed for the synthesis of substituted acetonitriles by the cyanation of halo derivatives by acetone cyanohydrin in the presence of base and phase transfer catalysts.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2647–2648, November, 1989.     

Reaction of 2-hetaryl-2-(tetrahydro-2-furanylidene)acetonitriles with aldehydes

The reaction of 2-hetaryl-2-(tetrahydro-2-furanylidene)acetonitriles with a electrophilic reagent (anisaldehyde) was studied. It was shown that condensation of the latter with 2-(4-oxo-3,4-dihydro-2-quinazolyl)- and 2-(1H-benzo[d]imidazol-2-yl)-2-(tetrahydro-2-furanylidene)acetonitriles in the presence of secondary amines or acids takes place with elimination of the furan fragment and the formation of 3-aryl-2-(4-oxo-3,4-dihydro-2-quinazolinyl)- and 2-(1H-benzo[d]imidazol-2-yl)acrylo-nitriles.     

Efficient solvent-free selective monoalkylation of arylacetonitriles with mono-, bis-, and tris-primary alcohols catalyzed by a Cp*Ir complex

Our objectives were to develop catalytic atom-economic processes accessing and/or incorporating versatile functionality using aryl/heteroaryl acetonitriles as substrates. We report essentially solvent-free [Cp*IrCl2]2 catalyzed redox neutral processes whereby substituted acetonitriles react with primary alcohols to deliver monosubstituted aryl/heteroaryl acetonitriles in excellent yield. We further demonstrate that such processes can be achieved by conventional or microwave heating and that bis- and tris-primary alcohols are also processed efficiently.     

Pyrrolo[3,4‐e][1,2,3]triazolo[1,5‐a]pyrimidine and pyrrolo[3,4‐d] [1,2,3]triazolo[1,5‐a]pyrimidine. New tricyclic ring systems of biological interest

Derivatives of the new ring system pyrrolo[3,4‐e][1,2,3] triazolo[1,5‐a]pyrimidine 6 were prepared in high yields in one step by reaction of 3‐azidopyrrole 3 and substituted acetonitriles. Compound 6b rearranged, upon heating in dimethyl sulfoxide in the presence of water, to pyrrolo[3,4‐d][1,2,3]triazolo‐[1,5‐a]pyrimidine 7.     

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.