Search

Upon treatment with H2O2/KOH in EtOH or with Na2CO3/H2O2 in acetone, cycloalkylidene-α-(4-arylthiazol-2-yl)acetonitriles afforded 2-(4-arylthiazol-2-yl)-1-oxaspiro[2.5]octane-2-carboxamides and 2-(4-arylthiazol-2-yl)-1-oxaspiro[2.4]heptane-2-carboxamides in excellent yields (76–100%). J. Heterocyclic Chem., 2011.

It is demonstrated, that 1,3-benzoxazin-4-ones react with Vilsmeier reagent to give chromene derivatives in generally good yields.

A novel one-pot procedure for accessing the comparatively little studied title compounds (III) is reported.

We offer a systematic and generalized review of literature data over the previous 10 years regarding the synthesis of monocyclic and condensed 1,3,5-thiadiazine derivatives under the conditions of Mannich reaction.

A reaction of N-methylmorpholinium 6-amino-4-aryl-3,5-dicyano-1,4-dihydropyridine-2-selenolates with primary amines and excess of formaldehyde leads to 3,5,7,11-tetraazatricyclo[7.3.1.02,7]tridec-2-ene-8-selenone derivatives. The same compounds were obtained by a multicomponent cascade cyclocondensation of benzaldehyde, cyanoselenoacetamide, primary amine, and excess of formaldehyde.

Cyanothioacetamide reacts with pyrazole-3(5)-diazonium chlorides to afford pyrazolo[5,1- c ][1,2,4]triazine-3-carbothioamides 5 . The latter can be oxidized with H 2 O 2 to give either pyrazolo[5,1- c ][1,2,4]triazine-3-carboxamides or 1,2,4-thiadiazole derivatives, depending on the reaction conditions. The Hantzsch-type reaction of thioamides 5 with α-bromo ketones leads to 3-(thiazol-2-yl)pyrazolo[5,1- c ][1,2,4]triazines.

Reaction of cyanoselenoacetamide with 1,3-dicarbonyl compounds bearing 2-anilinomethylene derivatives provides access to a variety of novel pyridine- and guinoline-containing selenium compounds as structural analogous of biologically active substances.

The title compounds (V) are obtained by a mediated Hantzsch-type multicomponent reaction of cyanoselenoacetamide (I) with aromatic aldehydes and 1,3-cyclohexanedione in the presence of an excess N-methylmorpholine.

Brief heating of 3-aryl-2-cyanothioacrylamides in the DMSO–HCl system gave (2E,2′E)-2,2′-(1,2,4-thia-diazol-3,5-diyl)bis(3-arylacrylonitriles). Under the same conditions, cyclic thioamides (derivatives of 2-thioxo-1,2-dihydropyridine-3-carbonitrile and quinoxaline-2(1H)-thione) gave good yields of the bis(hetaryl) disulfides. Ethyl 4-(4-chlorophenyl)-5-cyano-2-phenyl-6-thioxo-1,4,5,6-tetra-hydropyridine-3-carboxylate gave a mixture of oxidation products at the sulfur atom and the hetero-cycle when treated with the DMSO–HCl system. Oxidation of N-aryl-4,6-dimethyl-2-thioxo-1,2-di-hydropyridine-3-carboxamides gave isothiazolo[5,4-b]pyridines.

The interaction of 3-amino-3-thioxopropanamides with 2-anilinomethylene derivatives of dimedone, 1,3-cyclohexanedione and Meldrum’s acid led to the formation of 2-(2-amino-2-oxoethyl)-6-thioxo-1,6-dihydropyrimidine-5-carboxamides. The latter were alkylated in alkaline medium with the formation of 4-(alkylthio)pyrimidine-5-carboxamide derivatives.

Refluxing (I) with P4S10 in dry pyridine affords the title compounds as stable pyridine complexes.

Ethoxymethylene compounds are quite widely used in heterocyclic synthesis as three-carbon 1,3-dielectrophilic synthons [7, 8], but only isolated examples are known of their use in preparing selenium-containing compounds [9-11]. As has been noted [9], in contrast to their sulfur-containing analogs, the preparation of Se-containing derivatives in an analytically pure state can be difficult in such reactions.

β-Enaminocarbonyl compounds are commonly used in heterocyclic synthesis as convenient and readily available 1,3-dielectrophile 3C synthones [1, 2]. In previous work [3], we showed that the reaction of 5,5-dimethyl-2-phenylaminomethylidenecyclohexane-1,3-dione (1) with cyanothioacetamide gives the quinoline derivative 2. We established that the reaction of thiomalonamide 3 with dimedone derivative 1 yields 6-thioxopyrimidine-5-carboxamide 4 instead of the expected 3-carbamoyl analog of quinoline 2. Alkylation of carboxamide 4 with benzyl chloride gives benzyl derivative 5. The structures of carboxamides 4 and 5 were supported by IR, H-NMR, and C-NMR spectroscopy, HPLC/MS, elemental analysis, and the results of a H-C HMBC NMR experiment for carboxamide 4 (Fig. 1). The H NMR spectrum of carboxamide 4 shows signals for two amide groups and one methylene group, as well as singlets for protons H-4 and NH. The HPLC/MS shows a peak [M+H] with m/z 213.6. Atom H-4 in the pyrimidine ring in the H-C HMBC spectrum gives four correlation peaks: δ-8.78/127.1 (H-4/C-5), 8.78/159.6 (H-4/C-2), 8.78/163.7 (H-4/5-CONH2), and 8.78/179.7 ppm (H-4/C-6). The CH2 group protons give two cross peaks: δ-3.69/159.6 (CH2/C-2) and 3.69/167.8 ppm (CH2/CO). The finding of cross peaks at δ 7.17/41.1

The Mannich reactions of (arylmethylidene)(cyano)selenoacetamides with primary amines and formaldehyde gave 3,7-disubstituted 8-R-3,4,7,8-tetrahydro-2H,6H-pyrimido[4,3-b]-[1,3,5]selenadiazine-9-carbonitriles. Alternatively, these compounds can be obtained by reactions of 4-R-2,6-diamino-4H-selenopyran-3,5-dicarbonitriles with primary amines and form-aldehyde or by multicomponent condensation of an appropriate aldehyde, cyanoselenoacet-amide, a primary amine, and formaldehyde.

Pyrido[2,1-b][1,3,5]thiadiazines are a rather rare type of condensed heterocyclic system [1-3], and only isolated studies reporting the preparation of this bicyclic system have been reported [4-6]. We have shown that treatment of the previously synthesized 4-methyl-6-oxo-2-thioxopiperidine-3-carbonitrile 1 [7] with primary amines in the presence of excess HCHO gives the previously unknown pyrido[2,1-b][1,3,5]thiadiazines 2a,b. The structure of compounds 2a,b was confirmed from H NMR and IR spectroscopy and from elemental analysis data. The potential of the method and its optimization will be the subject of further investigations.

The method is efficient procedure for the synthesis of 4-aryl substituted Guareschi imides.

The interest in the chemistry of selenium heterocycles is largely due to the broad spectrum of their biological activity [1, 2]. Derivatives of 1,3,5-selenadiazine form a relatively little studied class of heterocyclic compounds. The methods reported for preparation of the 1,3,5-selenadiazine ring have been based on the reaction of 1,3-dichloro-1,3-bis(dimethylamino)-2-azapropenylium chlorides with selenamides or selenoureas [3, 4], the multicomponent reaction of benzylamine, sodium hydroselenide, and formaldehyde with aryl selenoisocyanates in acid media [5], the recyclization of 1,3,5-oxaselenazine [6, 7], and the reaction of dialkyl(1-aryl-1-chloro-2-aza-1-propenylidene)immonium perchlorate with N-acylselenoureas [8]. Butler and Fox [9] have described the preparation of a selenadiazine derivative as the result of recyclization of a 1,2,4-selenadiazolium salt. Condensed derivatives of 1,3,5-selenadiazines have not been described in the literature.

Despite prior reports of several really effective catalytic and non-catalytic approaches towards Biginelli’s 3,4-dihydropyrimidin-2(1H)-ones, an overwhelming number of new catalysts for the Biginelli reaction have been recently published. Most of the catalysts are somewhat exotic, expensive, harmful and even uneffective in the absence of acidic additives. Herein we reduce the “yet-another-one-catalyst” idea to absurdity by proposing NaCl promotes the reaction that actually requires no catalyst, neither rare nor expensive.

Morpholinium 3-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-thiolate upon treatment with primary amines and a formaldehyde excess under mild conditions produces bis(pyrido[2,1-b][1,3,5]thiadiazin-7-yl)methane derivatives in good yields (67–87%).

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.

Ethyl 2-(N-morpholinyl)cyclopent-1-ene-1-carboxylate reacted smoothly with cyanothioacetamide to give morpholinium 4-cyano-1-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[c]pyridine-3-thiolate; the former when treated with N-benzyl-α-chloroacetamide gave either a S-alkyl derivative or cyclopenta[d]thieno[2,3-b]pyridine, depending on the reaction conditions. Under Mannich-type aminomethylation with primary amines and formaldehyde the above thiolate afforded derivatives of the previously unknown heterocyclic system, cyclopenta[g]pyrido[2,1-b][1,3,5]thiadiazine in 81–90% yields.

Publisher Summary It is noted that the derivatives of pyridine attract significant interest because of their great practical usefulness, primarily, due to their various biological activities. Among pyridine derivatives, the fused analogs are considered extremely important. These factors are supplemented with variations due to annulation at different positions of the heterocyclic fragments. Further, among these heterocyclic systems, thienopyridines occupy a special place. This chapter describes the synthesis, reactivity, and biological activities of isomeric thienopyridines. The chapter considers six isomeric thienopyridine structures characterized by different annulation modes— namely, (1) thieno[2,3- b ]pyridine, (2) thieno[3,2- b ]pyridine, (3) thieno[2,3- c ]pyridine, (4) thieno[3,2- c ]pyridine, (5) thieno[3,4- b ]pyridine, and (6) thieno[3,4- c ]pyridine. The high pharmacological potential of thienopyridine derivatives stimulates the elaboration of new ingenious methods, nonconventional approaches, and regio- and stereoselective procedures that essentially extends the synthetic scope of the chemistry of nitrogen heterocycles. The unexhausted potential of thienopyridine derivatives as synthons also attracts considerable attention of organic chemists, because such compounds allow transformations that have been previously inaccessible.

Reaction of 1-(cyanoacetyl)-3,5-dimethylpyrazole with (E)-2-cyano-3-(het)arylprop-2-enethioamides was used for the synthesis of N-methylmorpholinium 3,5-dicyano-4-(het)aryl-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolates for the first time. The latter were also obtained in a multicomponent one-pot mode via the condensation of cyanothioacetamide with corresponding aldehydes and above 1-cyanoacetylpyrazole in the presence of N-methylmorpholine under mild conditions. Thiolates 1 exist as a pair of cis/trans-diastereomers in different ratios (from 3:4 to 2:1).

The reaction of N-methylmorpholinium 5-alkoxy-carbonyl-4-aryl-3-cyano-2-oxo-1,4,5,6-tetrahydropyridine-2-thiolates with primary amines and formaldehyde under mild conditions afforded 7-substituted alkyl 9-aryl-5-cyano-2-oxo-4-thioxo-3,7-diazabicyclo[3.3.1]nonane-1-carboxylates in fair to good yields (52–74%).

The current state and prospects of development of the chemistry of isomeric thienopyridines (synthesis, chemical transformations, and biological activities) are analyzed. Particular attention is given to studies published in the last 10–15 years.

A new methodology for the synthesis of substituted tetrahydropyrido[3',2':4,5]thieno[3,2-b]pyridines and the mechanism of their formation are described.

The reaction of cyanothioacetamide with a twofold molar excess of 1-(4-morpholino)cyclohexene in dry dioxane afforded previously unknown 3-cyano-4-cyclohexanespiro-1,2,3,4,5,6,7,8-octahydroquinoline-2-thione. Its structure was established by X-ray diffraction analysis and IR and 1H NMR spectroscopy.

Simple methods for the synthesis of previously unknown sulfur-containing pyridin-2-ones and 5,6,7,8-tetrahydroquinolines from cyanothioacetamide and anilinomethylidene derivatives of cyclic 1,3-dicarbonyl compounds were developed. Structures and chemical transformations of compounds obtained were studied.