s-Triazine derivatives. 4. Some peculiarities of the reactions of dicarbethoxymethylenetriazine derivatives

2- (Carbethoxycyanomethylene)-4,6-dimethoxy-1,2-dihydro-s-triazine reacts with hydrochloric acid to give 2-(carbethoxycyanomethylene)-4,6-dioxohexahydro-s-triazine (I) and with boric acid to give a mixture of the first compound with 2-(carbethoxy-cyanomethylene)-4-oxo-6-methoxy-1,2,3,4-tetrahydro-s-triazine. The products of the reaction of 2,4,6-tris(dicarbethoxymethylene)hexahydro-s-triazine with aniline are 2-(dicarbanilidomethylene)-4-methyl-6-phenylamino-1,2-dihydro-s-triazine (43%), N,N-diphenylurea (18%), and malonic acid dianilide (18%). In aqueous dioxane in the presence of A1₂O₃ this compound is converted to 2,4-bis(dicarbethoxy-methylene)-6-methyl-1,2,3,4-tetrahydro-s-triazine, which reacts with liquid ammonia to give 2-(dicarbethoxymethyl)-4-amino-6-methyl-s-triazine.See [1] for Communication 3.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 684–687, May, 1981.     

1,2-Dihydrotriazinyl-N-oxy free radicals

Triazinyl-N-oxy free radicals, 2-methyl-2,4,6-triphenyl-1,2-dihydro-1,3,5-triazinyl-1-oxy (6a), 2,2,4,6-tetraphenyl-1,2-dihydro-1,3,5-triazinyl-1-oxy (6b), 2,2-dimethyl-4,6-diphenyl-1,2-dihydro-1,3,5-triazinyl-1-oxy (13), and 2,6-dimethyl-2,4-diphenyl-1,2-dihydro-1,3,5-triazinyl-1-oxy (14), in which the unpaired electron is delocalized over three nitrogen atoms, have been prepared and characterized. A method has been devised for introducing an N-oxide function into the triazinyl core. Then, by using a Grignard reagent, substitution α to the N-oxide group was achieved and the resulting 1,2-dihydrotriazine-N-oxide oxidized into the corresponding nitroxide. Solution EPR spectra exhibit hyperfine splitting that confirms spin delocalization over the three nitrogen atoms of the triazinyl ring. They also show that spin delocalization diminishes with increasing distance for the coupling and is largest for nitrogen N1 and weakest for N5. Free radicals 6a and 13 are stable in the solid state and have been characterized by X-ray diffraction, but they tend to gradually degrade in solution. In the solid state, these two free radicals are arranged into antiferromagnetically exchange-coupled pairs, J=-5.2(6) for 6a and -3.7(4) cm(-1) for 13 (H=-2JS(1)S(2)).     

Derivatives of 2-benzazepine-1,3-dione

The reactions of the di(acid chloride) of 2-carboxy-3,4-dimethoxyphenylthiopyruvic acid with 1-aminoadamantane and with thiosemicarbazide take place with the closure of a seven-membered ring and the formation of 1,2-dihydro-(3H)-2-benzazepine-1,3-dione. On reaction with monochloroacetic acid, 4-mercapto-8, 9-dimethoxy-2-(N-thioureido)-1, 2-dihydro-(3H)-2-benzazepine-3-dione is converted into a derivative of thiazolidine-2,4-dione 2-hydrazone, which readily takes part in condensation reactions with oxo compounds forming 5-ylidene derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 29–32, January, 1984.     

On the synthesis of 3,4-dihydro-2H-1,2-benzothiazine 1,1-dioxides

The 3,4-dihydro-2H-1,2-benzothiazine 1,1-dioxides were prepared by reduction of the corresponding 1,2-benzothiazin-2-ones with diborane. The latter were obtained by the action of primary amines on 4,5-dimethoxy-2-carbomethoxymethylbenzenesulfonyl chloride followed by basic hydrolysis and cyclization of the formed 4,5-dimethoxy-2-carbomethoxymethylbenezenesulfonamides.     

Studies on cardiotonic agents. V. Synthesis of 1-(6,7-dimethoxy-4-quinazolinyl)piperidine derivatives carrying various 5-membered heterocyclic rings at the 4-position

A series of 1-(6,7-dimethoxy-4-quinazolinyl)piperidines carrying various 5-membered heterocycles at the 4-position was synthesized and examined for cardiotonic activity in anesthesized dogs. The (4-oxo-2-thioxo-3-imidazolindinyl)amino derivatives showed the most potent inotropic activity. Marked loss of activity was observed in the 2,4-dihydro-3-thioxo-3H-1,2,4-triazolyl, the 2,4-dihydro-3-oxo-3H-pyrazolyl and the (2,3-dihydro-2-thioxo-3H-1,3,4-thiadiazol-5-yl)amino derivatives. The synthesis and structure-activity relationships are discussed.     

An efficient synthesis of 6-formyl-1,2-dihydro-2-oxo-3-pyridinecarboxylic acid and some carbonyl derivatives of it and its 6-acetyl homologue

Starting with 1,1-dimethoxy-2-propanone ( 1 ), 6-formyl-1,2-dihydro-2-oxo-3-pyridinecarboxylic acid ( 5a ) has been prepared in large quantities by a highly efficient, 4-step synthesis. This compound, along with its one carbon homologue, 6-acetyl-1,2-dihydro-2-oxo-3-pyridinecarboxylic acid ( 5b ) has been reacted with several carbonyl derivative forming reagents to provide a series of side chains for β-lactams. Among these carbonyl derivatives are styrylamides which were prepared from Wittig and Horner-Emmons reagents. The preparation of the phosphonium salts and phosphonate esters is also described.     

Electron impact mass spectral fragmentation patterns of 2a,4-disubstituted 5-benzoyl-2-chloro-2a,3,4,5-tetrahydroazeto[1,2-a][1,5]benzodiazepin-1( 2H)-ones

The mass spectrometric behaviour of six 2a,4-disubstituted 5-benzoyl-2-chloro-2a,3,4,5-tetrahydroazeto[1,2-a][1,5]benzodia zepin-1(2H)-ones has been studied with the aid of mass-analysed ion kinetic energy spectrometry and accurate mass measurements under electron impact ionization. All compounds show a tendency to eliminate a chlorine atom, a chlorine atom plus benzaldehyde, benzoyl radical, chloroketene or chlorine atom plus CO and H2O molecules to yield, respectively, [M-Cl]+ ions, 2a,4-disubstituted 2a,3-dihydroazeto[1,2-a][1,5]benzodiazepin-1(2H)-one ions, [M-PhCO]+ ions, 2,4-disubstituted 1-benzoyl-2,3-dihydro-1H-1,5-benzodiazepine ions, or 1,2,4-trisubstituted 1H-1,7-benzodiazonine ions, which could also be formed from [M-Cl]+ ions by loss of CO and H2O molecules simultaneously. The [M-Cl]+ ions could further lose benzoyl radical to form [M-Cl-PhCO]+ ions, or lose benzoyl amide and undergo a rearrangement to form 4,6-disubstituted 1-benzoazocine-2(1H)-one ions. The [M-PhCO]+ ions could eliminate NH to produce 2a,4-disubstituted 2,2a,3,4-tetrahydroazeto[1,2,-a]quinolin-1-one ions, which could further eliminate chloroketene, CO and/or HCl to produce some important ions, respectively. 2,4-Disubstituted 1-benzoyl-2,3-dihydro-1H-1,5-benzodiazepine ions could lose benzoyl radical to yield 2,4-disubstituted 2,3-dihydro-1H-1,5-benzodiazepine ions, which could further yield other small fragment ions by loss of propene/styrene or small fragments.     

Three-component reaction of methyl 2,4-dioxo-4-phenylbutanoate and methyl 2,4-dioxopentanoate with aromatic aldehydes and propane-1,2-diamine and chemical properties of the products

The reactions of methyl 2,4-dioxo-4-phenylbutanoate and methyl 2,4-dioxopentanoate with a mixture of an aromatic aldehyde and propane-1,2-diamine, depending on the initial reactant ratio, gave 4-acyl-1-(2-aminopropyl)-5-aryl-3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones and 1,1′-(propane-1,2-diyl)bis(4-acetyl-3-hydroxy-5-phenyl-2,5-dihydro-1H-pyrrol-2-one). Reactions of substituted 1-(2-aminopropyl)-2,5-dihydro-1H-pyrrol-2-ones with aromatic amines and hydrazines were studied, and the structure of one of the products, 5-(2-aminopropyl)-3,4-diphenylpyrrolo[3,4-c]pyrazol-6-one, was proved by X-ray analysis.     

Bisbenzopyrans and alkaloids from the roots of Stemona cochinchinensis

Two new bisbenzopyrans, namely 3,3'-bis(3,4-dihydro-4-hydroxy-6,8-dimethoxy-2H-1-benzopyran) (1), and 8'-methoxy-3,3'-bis(3,4-dihydro-4-hydroxy-6-methoxy-2H-1-benzopyran) (2), together with known 3,3'-bis(3,4-dihydro-4-hydroxy-6-methoxy-2H-1-benzopyran) (3), as well as three known pyrido[1,2-alpha]azapine alkaloids, stemokerrin (4), oxystemokerrin (5) and oxystemokerrin-N-oxide (6), were isolated and identified from the roots of Stemona cochinchinensis. The structures of these compounds were elucidated by 1D- and 2D-NMR spectra and other spectroscopic studies.     

Fused s-triazino heterocycles. XVII. 8,13-Dihydro-1,3,7,8,13c-pentaazabenzo[de]naphthacene, 7H-1,3,7,8,11b,12,14-heptaazadibenzo[de,hi]naphthacene and 8H-1,3,7,8,13,14c-hexaazabenzo[4,5]cyclohepta[1,2-a]phenalene,three new ring systems

The reaction of 7,9-dibromo-5-tribromornethyl-2-t-butyl-4-cyano-1,3,6,9b-tetraazaphenalene ( 1a ) with p-toluidine is shown to give 4,6-dibromo-2-t-butyl-8,13-dihydro-13-imino-11-methyl-1,3,7,8,13c-pentaazabenzo[de]naphthacene ( 4 ) in two steps with 7,9 dibromo-2-t-butyl-4-cyano-5-p-toluidino-1,3,6,9b-tetraazaphenalene ( 2b ) as the intermediate product. A related annulation reaction of 1a with N-(5-amino-2,4-dimethylphenyl)trimethylacetamide ( 8 ) leads in two steps to 9,11-dibromo-2,13-di-t-butyl-4,6-dimethyl-7H-1,3,7,8,11b,12,14-heptaazadibenzo[de,hi]naphthacene ( 6 ) with 7,9-dibromo-2-t-butyl-4-cyano-5N-(2,4-dimethyl-5-trimethylacetamidophenyl)amino-1,3,6,9b-tetraazaphenalene ( 2d ) as the intermediate product. In a similar fashion the reaction of 1a with o-phenylenediamine forms 14-amino-4,6-dibromo-2-t-butyl-8H-1,3,7,8,13,14c-hexaazobenzo[4,5]cyclohepta[1,2-a]-phenalene ( 12 ) by way of the intermediate 5-N-(2-aminophenyl)amino-7,9-dibromo-2-t-butyl-4-cyano-1,3,6,9b-tetraazaphenalene ( 2e ). The preparation of N-(2,4-dimethyl-5-nitrophenyl)-trimethylacetamide ( 11 ) and its reduction to N-(5-amino-2,4-dimethylphenyl)trimethylacetamide ( 8 ) is also described.     

4-Hydroxy-2-quinolones. 180*. Synthesis,chemical reactions,and analgesic activity of 1-allyl-4-hydroxy-6,7-dimethoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid alkylamides

A targeted synthesis was carried out of a series of 1-allyl-4-hydroxy-6,7-dimethoxy-2-oxo-1,2-di-hydroquinoline-3-carboxylic acid alkylamides which show interest for biological study as potential analgesics. It was found that, in the presence of one equivalent of bromine, the compounds indicated undergo halocyclization to the corresponding 2-bromomethyl-7,8-dimethoxy-5-oxo-1,2-dihydro-5H-oxa-zolo[3,2-a]quinoline-4-carboxylic acid alkylamides. However, with an excess of bromine the reaction occurs somewhat differently and concludes with the formation of complexes of bromine with 4-alkyl-carbamoyl-2-bromomethyl-5-hydroxy-7,8-dimethoxy-1,2-dihydrooxazolo[3,2-a]quinolinium ditri- bromides. According to the results of pharmacological screening there are found compounds within the substances discovered with high analgesic activity.     

Acetals and Vinyl Ethers of Unsaturated Aldehydes and Ketones in the New Syntheses of Heterocyclic Compounds: XII. New Alternatives of Acid Condensation of Cyclohexane-1,4-diones with Hydroxyarylaldehydes under Dehydration Conditions. Fluorecence Spectra of the Products

1,3-Diethoxy-2-R-5,5-R',R'-1-cyclohexenylium perchlorates in condensation with 2-hydroxyarylaldehydes under dehydration conditions give rise to 3-ethoxy-1,2-dihydroxanthylium perchlorates that with the second molecule of 2-hydroxyarylaldehyde afford 13H-chromeno[3,2-b]xanth-5-ylium perchlorates, and with primary and secondary amines yield 3-(R²,R³-amino)-1,2-dihydroxanthylium perchlorates. The condensation of 2-bromodimedone with salicylaldehydes in triethyl orthoformate and perchloric acid medium furnished 6-bromo-13,13-dimethyl-13H-chromeno[3,2-b]xanth-5-ylium perchlorates. The latter compounds show strong fluorescence in 530-630 nm region with 0.48-0.98 quantum efficiency. Under similar conditions the dimedone and 2-acetyldimedone afford with 2-hydroxyarylaldehydes tris-condensation products: 2,10-dimethoxy-6-(3-methoxy-6-oxo-2,4-cyclohexadienylidenemethyl)-7,7-dimethyl-7H-chromeno[2,3-a]-xanth-13-ylium perchlorate and 2,10-dimethoxy-6-(6-methoxychromylium-2-yl)-13,13-dimethyl-13H-chromeno[3,2-b]xanth-5-ylium diperchlorate respectively.     

Pyrolysis of aminonitriles,cyanohydrazones, and cyanoacetamides. Part I. Elimination reaction of 1-arylmethyleneamino-1,2-dihydro-4,6-dimethyl-2-oxopyridine-3-carbonitriles and substituted benzaldehyde cyanoacetylhydrazones

Pyrolysis of the Schiff bases of 1-arylmethyleneamino-1,2-dihydro-4,6-dimethyl-2-oxopyridine-3-carbonitriles (1–5) has been studied. These compounds eliminate via a six-membered transition state to produce substituted benzonitriles and 2-hydroxy-4,6-dimethylpyridine-3-carbonitrile. These eliminations are unimolecular first-order reactions. The kinetic data gave a good correlation with σ⁰ values of the substituents on the aryl group with ρ = 0.83 at 520 K. Utilization of the pyrolytic reaction in synthesis of various benzonitriles is considered, and mechanistic information has been obtained by comparing the kinetic data and product analysis of the Schiff bases with their open-chain substituted benzaldehyde cyanoacetylhydrazones (6–9) analogues. © 1996 John Wiley & Sons, Inc.     

Dithiobiuretes in reactions with electrophilic acetylenes. New derivatives of 1,3,5-dithiazines,-thiadiazines and-triazines as the products of competing reactions of nucleophilic cycloaddition

The nucleophilic addition of 2,4-dithiobiurete, 1- and 1,4-substituted 2,4-dithiobiuretes (2 a-e) with benzoylacetylene (1) has been studied. 2-(Benzoylmethyl)-4-(R¹-imino)-6-(R²-imino)dihydro-4H-1,3,5-dithiazinium perchlorates (3 a-e) are obtained in glacial acetic acid (AcOH) in the presence of equimolar quantities of HClO₄. The reaction of benzoylacetylene with 1,5-diphenyl-2,4-dithiobiurete in either of MeOH, C₆H₆, or MeCN solvents proceeds non-selectively to give a mixture of products such as 2-(benzoylmethyl)-4,6-di(phenylimino)dihydro-4H-1,3,5-dithiazine (5), 2-(benzoylmethyl)-4-(β-benzoylvinyl)thio-3-phenyl-6-(phenylimino)-3,6-dihydro-2H-1,3,5-thiadiazine (8), 2-(benzoylmethyl)-1,3-diphenylhexahydro-1,3,5-triazine-4,6-dithione (7) and N-(β-benzoylvinyl)-N-phenylthioureas (6).     

Synthesis of acenaphtho[1,2-x]heterocycles and spiro[acenaphthylene 1-isoxazoles]

Methyl (Z)-(1,2-dihydro-2-oxo-1-acenaphthylenylidene)acetate 1 gives with hydroxylamine the oximes 2 and the pyrrole derivative 4 , whereas with hydrazines affords the pyridazinones 5 and 6 . A pyridazine derivative 8 is also isolated from the reaction of (1,2-dihydro-2-oxo-1-acenaphthylenylidene)acetone 7 with hydrazine hydrate. Reaction between the spiro-derivative 9 and hydroxylamine hydrochloride gives oxime 10 , whereas Wittig olefination of 9 with ylide 11 yields compound 12 which by reaction with 2,4,6-trimethylbenzonitrile oxide ( 13 ) affords the dispiro-derivatives 14 . Finally from the reaction of acenaphthylene-1,2-quinone ( 17 ) with the bisylide 16 the acenaphtho[1,2-c]thiophene ( 18 ) is formed.     

4-Hydroxy-2-quinolones. 112. Reaction of 2-ethoxycarbonylmethyl-4H-3,1-benzoxazin-4-one with active methylene compounds

The reaction of 2-ethoxycarbonylmethyl-4H-3,1-benzoxazin-4-one with malononitrile in dry pyridine leads to 1-hydroxy-3,6-dioxo-4,6-dihydro-3H-pyrimido[1,2-a]quinoline-5-carbonitrile. Acetoacetic and cyanoacetic esters under analogous conditions form anilides of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid while diethyl malonate gives N,N′-di-2-carboxyanilides of malonic acid. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 75–79, January, 2007.     

Synthesis of ethyl 2-aminodihydro-5-pyrimidinecar-boxylate derivatives and 3,7-diethoxycarbonyl-4,6-dihydro-2,4,6,8-tetraaryl-1H-pyrimido[1,2-a]pyrimidines

Reactions of ethyl 3-aryl-2-benzoylpropenoates 1 with guanidine and N-alkyl(or benzyl)guanidines have been investigated. Ethyl 2-aminodihydro-5-pyrimidinecarboxylate derivatives 3, 4 or 5, and 3,7-diethoxy-carbonyl-4,6-dihydro-2,4,6,8-tetraaryl-1H-pyrimido[1,2-a]pyrimidines 6 have been synthesized.     

Synthesis, structure, and heck cyclization of the syn- and anti-atropisomers of N-acyl-N-(4-methyl-3,6-dihydro-2H-pyran-3-yl)-2-iodo-4,6-dimethylaniline

The reaction of 2-iodo-2,4-dimethylaniline with 3,4-dibromo-4-methyltetrahydro-2H-pyran, followed by treatment with acetyl bromide or 4-nitrobenzoyl chloride, gave syn- and anti-atropisomers of N-(2-iodo-4,6-dimethylphenyl)-N-(4-methyl-3,6-dihydro-2H-pyran-3-yl)acetamide and N-(2-iodo-4,6-dimethylphenyl)-N-(4-methyl-3,6-dihydro-2H-pyran-3-yl)-4-nitrobenzamide. Heating of the acetamide derivative with palladium(II) acetate in the presence of copper(II) acetate and N,N,N′,N′-tetramethylethane-1,2-diamine resulted in heterocyclization to N-acetyl-4a,6,8-trimethyl-1,4a,9,9a-tetrahydropyrano[3,4-b]indole.     

Chemistry of acyl(imidoyl)ketenes. 8*. Thermolysis of 3-alkoxycarbonyl- 5-phenyl-1,2,4,5-tetrahydropyrrolo[1,2-a]- quinoxaline-1,2,4-triones. Structure of 2-(3-oxo-4-phenyl-3,4-dihydro-2-quinoxalinyl)- 2,4-di(ethoxycarbonyl)-6-phenyl-2,3,5,6-tetrahydro- 1h-pyrido[1,2-a]quinoxaline-1,3,5-trione

3-Alkoxycarbonylmethylene-1-phenyl-1,2,3,4-tetrahydro-2-quinoxalones, obtained by the interaction of dialkyl esters of oxaloacetic acid and N-phenyl-o-phenylenediamine, react with oxalyl chloride with the formation of 3-alkoxycarbonyl-5-phenyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinoxaline-1,2,4-triones. Alkoxycarbonyl(2-oxo-1-phenyl-1,2-dihydro-3-quinoxalinyl)ketenes, generated on thermal decarbonylation of the latter, are stabilized by participation in a [4+2] cyclodimerization reaction with the formation of 2,4-di(alkoxycarbonyl)-2-(3-oxo-4-phenyl-3,4-dihydro-2-quinoxalinyl)-6-phenyl-2,3,5,6-tetrahydro-1H-pyrido[1,2-a]quinoxaline-1,3,5-triones. The crystal and molecular structure of the di(ethoxycarbonyl) derivative have been investigated by X-ray structural analysis.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1501–1506, October, 2004.     

Quino[1,2-c]quinazolines. II. Synthesis of 12,13-dihydro-11bH-quino-[1,2-c]quinazolines via the versatile intermediates 2-(2-amino-4,5-dimethoxyphenyl)-6,7-disubstituted-1,2,3,4-tetrahydroquinolines

The versatile intermediates 2-(2-amino-4,5-dimethoxyphenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroquinoline ( 2a ) and 6-(2-amino-4,5-dimethoxyphenyl)-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]quinoline ( 2b ) were used in the preparation of a wide variety of 12,13-dihydro-11bH-quino[1,2-c]quinazolines by reaction with triethyl orthoformate, cyanogen bromide, urea and carbon disulfide in pyridine. Reaction of the thio and keto products with methyl iodide and phosphorus oxychloride, respectively, gave the requisite methylthio and chloro derivatives. Novel Reissert type reactions occurred when the intermediates 2a,b were reacted with acetic anhydride or benzoyl chloride. The attempted dehydrogenation of 12,13-dihydro-2,3,9,10-tetramethoxy-11bH-quino[1,2-c]quinazoline ( 3a ) is also reported.