Vera S. Berseneva

Reaction of heterocyclic thioamides with dimethyl acetylenedicarboxylate. Synthesis of novel 2-azolyl-5-methoxycarbonylmethylene thiazolin-4-ones

Abstract A systematic study of the reactions of dimethyl acetylenedicarboxylate (DMAD) with heterocyclic thioamides has been carried out and a number of new 2-isoxazolyl-( 8 ), imidazolyl-( 13a , b and 17a ), 1,2,3-triazolyl-( 13d , e ) and 1,2,3-thiadiazolyl ( 17b ) thiazolines have been prepared. The higher reactivity of the thioamide group in comparison with the amino group in these reactions has been established.

Synthesis of novel thiazolidin-4-ones by reaction of malonthioamide derivatives with dimethyl acetylenedicarboxylate

Novel 2,5-dimethylenethiazolidin-4-one derivatives have been prepared by reaction of malonthioamide derivatives with dimethyl acetylenedicarboxylate. These compounds exist as separate (E,Z)- and (Z,Z)-isomers or as a mixture. The (E,Z)-isomer is formed as the initial product which transforms to the (Z,Z)-isomer under mild conditions. The structures of the obtained compounds have been confirmed by IR and NMR spectroscopy.

Switchable Synthesis of 4,5-Functionalized 1,2,3-Thiadiazoles and 1,2,3-Triazoles from 2-Cyanothioacetamides under Diazo Group Transfer Conditions

High yield solvent-base-controlled, transition metal-free synthesis of 4,5-functionalized 1,2,3-thiadiazoles and 1,2,3-triazoles from 2-cyanothioacetamides and sulfonyl azides is described. Under diazo transfer conditions in the presence of a base in an aprotic solvent 2-cyanothioacetamides operating as C-C-S building blocks produce 5-amino-4-cyano-1,2,3-thiadiazoles exclusively. The use of alkoxide/alcohol system completely switches the reaction course due to the change of one of the reaction centers in the 2-cyanothioacetamide (C-C-N building block) resulting in the formation of 5-sulfonamido-1,2,3-triazole-4-carbothioamide sodium salts as the only products. The latter serve as good precursors for 5-amino-1,2,3-thiadiazole-4-carboximidamides, the products of Cornforth-type rearrangement occurring in neutral protic medium or under acid conditions. According to DFT calculations (B3LYP/6-311+G(d,p)) the rearrangement proceeds via intermediate formation of a diazo compound, and can be catalyzed by acids via the protonation of oxygen atom of the sulfonamide group.

Reactions of Malonothioamide Derivatives with Azides

The reactions of primary and tertiary malonothioamides with aryl and sulfonyl azides can take place in three directions, depending on the nature of the thioamides and azides. Ethoxycarbonylthioacetamide reacts with aryl azides with the formation of ethyl 5-amino-1-aryl-1,2,3-triazole-4-carboxylates. In reaction with aryl azides tertiary thioamides of cyanoacetic acid form 5-amino-1-aryl-1,2,3-triazole-4-carbothioamides, and in reaction with tosyl azide they form 5-amino-4-carboxamidino-1,2,3-thia-diazoles. Hypothetical mechanisms for the transformations are discussed.

Synthesis of fluoroquinoxalin-2(1H)-one derivatives containing substituents in the pyrazine and benzene fragments

Abstract6,7-Difluoroquinoxalin-2-one reacted with indoles, 5,5-dimethylcyclohexane-1,3-dione, 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one, resorcinol, and pyrogallol on heating in acetic acid to give products of hydrogen substitution in the heterocyclic fragment. Heating of 6,7-difluoro-3-(1H-indol-3-yl)quinoxalin-2(1H)-ones with N-methylpiperazine gave the corresponding 7-(4-methylpiperazin-1-yl) derivatives.

Multi-Component Reactions in Supramolecular Chemistry and Material Science

Multi-component reactions of building blocks with more than one MCR-reactive group will give rise to oligomeric MCR products. The proper choice of at least two bifunctional building blocks will give either a polymeric or a cyclic product. Apart from polymerization, repetitive or consecutive Ugi reactions have been used to produce linear MCR-heterooligomers with such building blocks.

Reaction of 5-Nitroso-6-Aminouracils with Glyoxylic Acid – A Simple Synthetic Pathway to Uric Acid Derivatives

Purines are commonly synthesized by the method proposed by Traube that is based on cyclization of 4,5-aminopyrimidines with urea, formamide, or formic acid [1]. The reaction of 4,5-aminopyrimidines with C2 cyclizing agents (glyoxal, glyoxylic acid derivatives, etc.) synthesized pteridine derivatives [1, 2]. Heating 5-nitroso-6-aminouracils with aldehydes formed 7-hydroxyxanthine derivatives [3]. Uric acid is the final product from oxidation (metabolism) of purines in living organisms. Its level characterizes the metabolic condition. Serious diseases can manifest if its in vivo content increases. Therefore, monitoring of the secretion level of uric-acid and its derivatives is especially significant [4]. Practically the whole set of natural purine bases or the nucleic acids incorporated into the structure or resulting from purine metabolism can be synthesized from uric acid [1]. The reactions of uracil amine derivatives with C2 cyclizing agents were investigated in order to develop simple and convenient synthetic pathways to purine and pteridine derivatives. An unusual transformation of 5-nitroso-6-aminouracils 1a and 1b during the reaction with glyoxylic acid was discovered during the work. Thus, brief heating of 1a and 1b and glyoxylic acid in formic acid formed smoothly and in high yield uric-acid derivatives 2a and 2b (Scheme 1).

Transformations of 6,7-difluoroquinoxaline with Indoles: Synthesis of Indole-Substituted 6,7-difluoroquinoxalines and Tris(indol-3-yl)methane Derivatives

6,7-Difluoroquinoxaline (1) reacted with 1- and 2-methylindoles (2a and 2b) with heating in AcOH to give products from substitution of H in the heterocyclic fragment (3a and 3b) and tris(indol-3-yl)methane derivatives (4a and 4b).

New reactions of benzocaine

Reaction of benzocaine with indane-1,3-dione-2-carbaldehyde afforded the corresponding azomethine. Ethoxymethylenemalonate reacted with benzocaine to form ethyl 4-{[2-(ethoxycarbonyl)-4-methoxy-3-oxobuten-1-yl]amino}benzoate, which was converted to the corresponding quinolone when heated to 185–190°C. Reactions of benzocaine with aliphatic aldehydes furnished 2,3-alkyl-substituted quinolines.

Tandem Knoevenagel Condensation and Intramolecular Cycloaddition Reactions of 2-Azidobenzaldehydes with 2-Cyanoacetamides in the Synthesis of 4-Thiocarbamoyltetrazolo-[1,5-a]Quinolines

The reaction of 2-azidobenzaldehydes with 2-thioamides of cyanoacetic acid proceeds without a solvent and base at 80–90°C selectively by one of the possible routes to form tetrazolo[1,5-a]quinolines. The proposed mechanism of the reaction involves the Knoevenagel condensation and subsequent intramolecular [3+2] cycloaddition of the azide group at the C≡N bond of an intermediate acrylonitrile.