Rearrangement reactions of aziridinylbenzaldoximes

Reactions of 2,2-dimethylaziridine with benzohydroximoyl chlorides [ArC(Cl)?NOH] give aziridinylbenzaldoximes 1 . It has been found that the aziridine ring in these compounds undergoes ring opening in hydrogen chloride-dioxane solution to give (Z)-N-hydroxy-N′-(2-chloro-2-methylpropyl)benzenecarboximidamides [ArC(NHCH₂CR¹R²Cl)?NOH, 4 ]. Treatment of 1 with hydrochloric acid followed by neutralization with aqueous sodium hydroxide gave 6,6-dimethyl-3-aryl-1,2,4-oxadiazines 2. Reaction of 4 with sodium hydride in dioxane gave 5-isopropyl-3-aryl-4,5-dihydro-1,2,4-oxadiazoles 5. Reaction of the 4,5-dihydro-1,2,4-oxadiazoles 5 with N-chlorosuccinimide gave the heteroaromatic 1,2,4-oxadiazoles 6 . It is suggested that reactions of 4 with sodium hydride in dioxane solution involve the conjugate base of 4 which undergoes a 1,2-hydride shift that is concerted with loss of chloride ion. In aqueous sodium hydroxide solution it is suggested that the conjugate base of 4 undergoes ionization of the chlorine atom followed by nucleophilic attack by the oximate anion.     

Base promoted transformation on thiadiazolopyridinium chlorides

1,2,4-Thiadiazolo[2,3-a]pyridinium chlorides undergo a very facile base promoted transformation to give bispyridilimino-1,2,4-thiadiazolidines. The unequivocal structural assignment of these last compounds was achieved by spectroscopic ¹H, 13C and ¹⁵N two dimensional methods.     

Reactions of 2-(4,5-dihydro-3-furyl)-1,3-diphenyl-1,3-diaza-2λ<Superscript>3</Superscript>-phospholidine and 4,5-dihydro-3-furylphosphonous diamides with nitrile imines

Reactions of 2-(4,5-dihydro-3-furyl)-1,3-diphenyl-1,3-diaza-2λ³-phospholidine (1) with nitrile imines are multistep processes involving cleavage of one P-N bond of the diazaphospholidine ring to form substituted 5-(2-chloroethyl)-4-(N,N′-diphenylethylenediamino)-1,4-dihydro-1,2,4λ⁵-diazaphosphorines 4 as final products. Analogs of phospholidine 1, namely, 4,5-dihydro-3-furylphosphonous dipiperidide and dimorpholide, react with C,N-diphenylnitrile imine with retention of both P-N bonds to give 5-(2-hydroxyethyl)-1,2,4-diazaphosphorinium chlorides. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1590–1593, July, 2005.     

Synthesis of 3-carbamoyl-1,2,4-oxadiazoles

A convenient method for the synthesis of 3-carbamoyl-1,2,4-oxadiazoles from carbamoylamidoximes and chlorides or anhydrides of haloacetic acids was developed. The reactions of 3-carbamoyl-5-trichloromethyl-1,2,4-oxadiazoles with amines and N,N-dimethylhydrazine were studied.     

Notiz über die Reaktion von Methylhydrazin mit N-Cyano-azomethinen. Abhängigkeit des Reaktionsverlaufs von der Natur der Abgangsgruppe

The reaction of methylhydrazine with N-cyanoazomethines 1 containing a thioalkyl leaving group yields the 3-amino-1,2,4-triazole derivatives 2 , whereas the N-cyanoazomethines 1 containing an alkoxy leaving group give the isomeric 5-amino-1,2,4-triazoles 3. The yields are excellent and the position selectivity is high. The structures of the 1,2,4-triazole derivatives were determined with the aid of proton-coupled ¹³C-NMR. spectra.     

Regioselectivity in the Reactions of Bis -hydrazonoyl Halides with Pyrimidine-2-thiones

 Bis-hydrazonoyl chlorides react regioselectively with pyrimidine-2-thiones, which contain a masked thiourea residue, to give the hitherto unknown annelated 2,3-bis-arylhydrazono-thiazoles and 3,3′-bis-1,2,4-triazoles. Reaction of bis-hydrazonoyl chlorides with 2-methylthio derivatives gave only 3,3′-bis-1,2,4-triazoles.     

The Synthesis and Reactions of N-Hydroxy-3-Arylsydnone-4-Carboxamide Oximes

N-Hydroxy-3-arylsydnone-4-carboxamide oximes (7) were prepared from the corresponding 3-arylsydnone-4-carbohydroximic acid chlorides (6) and hydroxylamine in high yield. The chemical reactivity of compound (2) is somewhat different from 3-arylsydnone-4-carboxamide oximes (2) in that the former compounds reacted with both aromatic and aliphatic aldehydes in the presence of acid catalyst to give 3-aryl-4-(5-aryl-1,2,4-oxadiazol-3-yl)sydnones (5) and 3-aryl-4-(5-alkyl-1,2,4-oxadiazol-3-yl)sydnones (3).     

Regioselectivity in the Reactions of Bis-hydrazonoyl Halides with Pyrimidine-2-thiones

Summary.  Bis-hydrazonoyl chlorides react regioselectively with pyrimidine-2-thiones, which contain a masked thiourea residue, to give the hitherto unknown annelated 2,3-bis-arylhydrazono-thiazoles and 3,3′-bis-1,2,4-triazoles. Reaction of bis-hydrazonoyl chlorides with 2-methylthio derivatives gave only 3,3′-bis-1,2,4-triazoles. Received October 4, 2000. Accepted (revised) December 20, 2000     

Synthesis of heterocycles. Part VI. Synthesis and antimicrobial activity of some 4-amino-5-aryl-1,2,4-triazole-3-thiones and their derivatives

4-Amino-5-aryi-1,2,4-triazole-3-thiones I react with acid chlorides to yield 4-acylamino-5-aryl-1,2,4-triazole-3-thiones II. Compounds I also react with methylene iodide, chloroacetonitrile and methyl bromoacetate to give bis-(4-amino-5-aryl-1,2,4-triazol-3-ylthio)methanes III, 4-amino-5-aryl-3-cyanomethylthio-1,2,4-triazoles IV and 4-amino-5-aryl-3-carbomethoxymethylthio-1,2,4-triazoles V, respectively. Compounds V react with hydrazine hydrate to give the corresponding acid hydrazides VI which in turn condenses with acid chlorides and aldehydes to afford respectively 1-[(4-amino-5-aryl-1,2,4-triazol-3-ylthio)acetyl]-2-aroylhydrazines VII and aryl methylene (4-amino-5-aryl-1,2,4-triazol-3-ylthio)acethydrazones VIII. The antimicrobial activities of the above compounds were screened against different strains of bacteria and fungi.     

Synthesis of pyridyloxadiazoles 1. Characterization and thermal rearrangement of an unexpected 1,2,4-oxadiazol-5(4H)one

The synthesis of pyridyloxadiazoles by the reaction of acid chlorides with 5-(2-pyrklyl)-tetrazole or 2-pyridineamidoxime was studied. Reaction of 2-pyridineamidoxime with N,N-dimethylcarbamyl chloride produced 3-(2-pyridyl)-4-N,N-dimethylaminocarbony 1-1,2,4-oxadi-azol-5(4H)one instead of the expected oxadiazole. The oxadiazolone underwent thermal rearrangement with expulsion of carbon dioxide to yield the desired 3-(2-pyridyl)-5-N,N-dimethylamino-1,2,4-oxadiazole.     

Chlorination of isothiocyanates. V . 5-imino-1,2,4-thiadiazolidin-3-ones

S-[N'- (Chlorocarbonyl)amino]isothiocarbamoyl chlorides (II), obtained from S-chloroisothiocarbamoyl chlorides (I) and isocyanates, react with primary aliphatic and aromatic amines to form the unknown class of 5-imino-1,2,4-thiadiazolidin-3-ones. The structures were confirmed by chemical means and by spectroscopic methods.     

Reactions with Naphthoylhydroxlmoyl Chlorides: Synthesis of Derivatives of Isoxazole,Pyrrolidino[3,4-d]isoxazoiin-4,6-dione,lmidazo[1,2-a]pyridine,lmidazo[1,2-a]pyrimidine,Benzotriazine and Benzothiadiazine

Hydroximoyl chlorides 3 react with acrylonitrile, N-arylmaleimide and maleic anhydride to give isoxazolines 5 , pyrrolidino[3,4-d]isoxazolines 8 , and furolidino[3,4-d]isoxazolines 9 , respectively. 3 reacted with 2-aminopyridine, 2-aminopyrimidine, o-phenylenediamine and o-aminothiophenol to yield 3-ni-trosoimidazo[1,2-α]pyridines 20 , 3-nitrosopyrimidines 22 , 3-naphthoyl-1,4-dihydrobenzo-1,2,4-triazines 24 , and 3-naphthoyl-4H-1,3,4-benzothiadiazine 27 , respectively. Compound 3 reacted with benzoylacetonitrile, acetoacetanilide, thiophenol, benzencsulfinic acid in ethanolic sodium ethoxide solution to give the corresponding isoxazoles 12–13 and oximes 16–17 , respectively. The structures of these products were confirmed by elemental analyses, spectral data and, wherever possible, alternative synthesis.     

Asymmetric induction in the reactions of azinones with C-nucleophiles

Effect of acylating agents on the course of addition of C-nucleophiles to 1,2,4- and 1,3,5-triazinones, as well as to quinoxalin-2(1H)-one, was studied. A series of new azinone derivatives was obtained. A method for the preparation of diastereomerically pure addition products of indoles to 1,2,4-triazinones and quinoxalin-2(1H)-one in the presence of N-Ts-L-amino acid acyl chlorides was suggested.     

型2,3-二氢-3-芳亚甲基-4-芳基-1,5-苯并硫氮杂的合成及表征

在盐酸和乙醇存在下, 苯乙酮、多聚甲醛以及N,N-二甲基甲酰胺进行Mannich反应, 得到了Mannich碱; 将其和1,2,4-三唑在水中反应, 得到含有1,2,4-三唑的苯丙酮; 然后, 在哌啶和甲苯存在下, 苯丙酮和苯甲醛进行羟醛缩合, 得到一系列含有1,2,4-三氮唑的查尔酮; 最后, 在三氟乙酸的催化下, 查尔酮和邻氨基硫酚发生亲核取代反应, 然后脱水缩合, 合成了一系列2,3-二氢-3-芳亚甲基-4-芳基-1,5-苯并硫氮杂. 其结构经IR, ¹H NMR, MS及元素分析确证.     

Heterocyclization of Acetamidrazones. I. Synthesis of 1,2,4-triazolo[4,3-a]pyridines via ring closure of 6-(2-acylhydrazino)pyridine intermediates

The reaction of N¹-acyl-2-ethoxycarbonylacetamidrazones with ethyl ethoxymethylenecyanoacetate (EMCA) has been examined. The acetamidrazone 1a reacts with EMCA in boiling dimethyl sulphoxide to give the 1,2,4-triazolo[4,3-a]pyridin-3(2H)-one 2 in excellent yield. Similarly from the amidrazones 1b-h the 1,2,4-triazolo[4,3-a]pyridines 3b-h were obtained. When the reaction between the amidrazones and EMCA was performed in ethanolic solution, the 6-(2-acylhydrazino)-pyridines 4 were isolated. Ring closure of 4 afforded the 1,2,4-triazolo[4,3-a]pyridines.     

Regioselectivity of the reaction of 4H-1,2,4-triazole-3-thiol derivatives with chloroethynylphosphonates and structure of the products

Chloroethynylphosphonates reacted with 4H-1,2,4-triazole-3-thiols in anhydrous acetonitrile to afford fused heterocyclic compounds, 6-(dialkoxyphosphoryl)-3H-thiazolo[3,2-b][1,2,4]triazol-7-ium chlorides, with high regioselectivity. The products were converted into inner salts (zwitterions) of the corresponding phosphonic acids or their monoesters with the positive charge localized on N⁷. A probable reaction mechanism implies initial formation of sulfonium ion via attack by the thionic sulfur atom on the acetylenic carbon atom linked to chlorine, followed by intramolecular cyclization involving attack on the other acetylenic carbon atom by N² of the triazole ring.     

C-(β-d-Glucopyranosyl)formamidrazones,formic acid hydrazides and their transformations into 3-(β-d-glucopyranosyl)-5-substituted-1,2,4-triazoles: a synthetic and computational study

Synthesis of O-perbenzoylated 3-(β-d-glucopyranosyl)-5-substituted-1,2,4-triazoles, precursors of potent inhibitors of glycogen phosphorylase, was studied by ring closures of N¹-acyl-carboxamidrazone type intermediates. Reactions of C-(β-d-glucopyranosyl)formimidate or C-(β-d-glucopyranosyl)formamidine with acid hydrazides as well as acylation of C-(β-d-glucopyranosyl)formamidrazone by acid chlorides unexpectedly gave the corresponding 1,3,4-oxadiazoles instead of 1,2,4-triazoles. The desired triazoles were obtained in reactions of C-(β-d-glucopyranosyl)formamidine or C-(β-d-glucopyranosyl)formyl chloride with arenecarboxamidrazones, and also in acylations of N¹-tosyl-C-(β-d-glucopyranosyl)formamidrazone with acid chlorides. Theoretical calculations (B3LYP and M06-2X DFT with the standard 6-31G(d,p) basis set) on simple model compounds with methyl and phenyl substituents to understand the bifurcation of the ring closure of N¹-acyl-carboxamidrazones indicated that in general the reaction led to 1,2,4-triazoles. However, the probability of the 1,3,4-oxadiazole forming pathway was shown to be significantly higher with N¹-benzoyl-acetamidrazones, which were closest analogues of the intermediates resulting in C-glucosyl-1,3,4-oxadiazoles. It was thereby demonstrated that the substitution pattern of the N¹-acyl-carboxamidrazones played a fundamental role in determining the direction of the ring closing reaction.     

Synthesis of N-substituted pyrroles from 1-R-3-R1-3,4-dichlorobutanones

Reaction of acyl chlorides or methallyl chlorides in the present of aluminum chloride gives 1-R-3-R¹-3,4-dichlorobutanones which give 1,2- and 1,2,4-substituted pyrroles with ethanolamine. The dichlorobutanones react with glycine and -alanine to give the N-pyrrolyl derivatives of acetic and propionic acids.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1181–1184, September, 1990.     

Efficient synthesis and molecular docking of novel antibacterial pyrimidines and their related fused heterocyclic derivatives

3-(Benzo[d][1,3]dioxol-5-yl)-1-(thiophen-2-yl)prop-2-en-1-one reacted with each of thiourea and 6-amino-2-thioxo-2,3-dihydropyrimidin-4(1H)-one to give the corresponding pyrimidine-2(1H)-thiones. Then, these compounds reacted with the appropriate hydrazonyl chlorides in dioxane in the presence of triethylamine to afford the corresponding [1,2,4]triazolo[4,3-a]pyrimidines and their related fused pyridines. Moreover, chalcone was cyclocondensed with 2-cyanothioacetamide to give pyridine-2(1H)-thione and taken as a key synthon to novel 2-(methylthio)pyridothienopyrimidin-4(3H)-one derivative. The above derivative reacted with the appropriate hydrazonyl chlorides in dioxane in the presence of triethylamine to yield the corresponding pyridothieno[3,2-d][1,2,4]triazolo[4,3-a]pyrimidines. Study of the in vitro antimicrobial activities of the newly pyrimidines were performed. Pyridothienopyrimidine 24a showed the highest inhibitory activity against all bacteria with MIC values of 3.9, 7.81, 7.81, and 15.62 μg/mL, respectively, against Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and Streptococcus mutans, respectively, as compared to reference drugs. Molecular docking was studied to predict of the optimized conformation of pyrimidines as active ligands against the Escherichia coli alkaline phosphatase. The structures of the hybrid molecules were elucidated by IR, Mass, ¹H NMR, and ¹³C NMR spectra as well as elemental analyses.     

Alkylsulfamoyl Chlorides as Key Units in the Synthesis of Novel Biologically Active Compounds for Crop Protection

Due to their bifunctional character, alkylsulfamoyl chlorides are versatile units for the synthesis of heterocycles, polar sulfamates, and sulfonamides. In the last decade, synthetic methods of general preparative use have been developed, by means of which amine hydrochlorides, isocyanates, aziridines or tertiary alcohols can be reacted with suitable sulfuric acid derivatives to give novel, variously substituted alkylsulfamoyl chlorides. These compounds can subsequently be converted either to previously unobtainable N-alkoxyalkyl-N-alkylsulfamoyl chlorides or to novel heterocycles of the type 1H-2,1,3-benzothiadiazin-4-one-2,2-dioxide, 2H-1,2,6-thiadia-zin-3-one-1,1-dioxide and 2H-1,2,4,6-thiatriazin-5-one-1,1-dioxide; these compounds are examples of interesting models which illustrate the relation between the structure and the action of the compound, and in some cases lead to highly selective, ecologically unobjectionable herbicides. On the other hand, the alkylsulfamoyl chlorides themselves can be N-acylated to give further 3- to 5-atom bifunctional synthesis units, with which novel heterocyclic syntheses can be carried out. Further uses of the alkylsulfamoyl chlorides include the preparation of biologically active sulfamates, and cycloaddition reactions of N-sulfonylamines prepared in situ.