Synthesis and properties of 5-aroylamino-2H-1,2,4-thiadiazol-3-ones

5 -Aroylamino-2H-1,2,4-thiadiazol-3-ones 3 were obtained from the corresponding 1-aroyl-2-thiobiurets 2 by oxidative cyclization with bromine. 5 -Aroylamino-2H-1,2,4-thiadiazol-3-ones 3 can exist in two tautomeric forms a lactam form and a lactim form. On the basis of the ¹³C nmr spectra and additional experimental information, it has been established that the stable form, in which these compounds exist, is the lactam form.     

An Efficient Acylation of Free Glycosylamines for the Synthesis of N-Glycosyl Amino Acids and N-Glycosidic Surfactants for Membrane Studies

Abstract

Treatment of free glycosylamines with 3-acyl-5-methyl-1,3,4-thiadiazole-2 (3H)-thiones 6 or with acids and 5-methyl-2-thioxo-1,3,4-thiadiazole-3(2H)-carbothioic acid S-(5-methyl-1,3,4-thiadiazol-2-yl) ester 7 in hydroorganic media afforded N-acylglycosylamines in high yields and without any competitive deglycosylation. This reaction found applications in the synthesis of N-glycopeptide building blocks and of glycosidic non ionic surfactants. Results concerning surface activities of two N-acylglycosylamines are reported. The new non ionic N-octanoyl-β-D-glucosylamine surfactant exhibited efficacy and selectivity in the extraction of membrane proteins, enhanced the activity of a membrane succinate dehydrogenase and proved thus useful for membrane studies.     

The Tautomerism of 1,3,4-Thiadiazol-2 (3H)-ones. A 15N-NMR-Study

5-Substituted 1,3,4-thiadiazol-2(3H)-ones were shown to exist almost exclusively in the oxo tautomeric form with the aid of proton-coupled ¹⁵N-NMR spectra using the corresponding 3-methyl-1,3,4-thiadiazol-2(3H)-ones and 5-substituted-2-methoxy-1,3,4-thiadiazoles as reference compounds.     

Reactions of α-Halo Ketones with 5-Benzyl- and 5-Phenoxymethyl-2H,3H-1,3,4-oxadiazole-2-thiones

Alkylation of 5-substituted 2H,3H-1,3,4-oxadiazole-3-thiones with -bromo ketones in alkaline solutions yields 5-substituted 2-aroylmethylthio-1,3,4-oxadiazoles; in acidic solutions these compounds re- arrange into 4-aryl-3-arylacetamido-2H,3H-1,3-thiazol-2-ones.     

2-Azido-1,3,4-thiadiazoles, 2-Azido-1,3-thiazoles,and Aryl Azides in the Synthesis of 1,2,3-Triazole-4-carboxylic Acids and Their Derivatives

Diazotization of 2-amino-1,3,4-thiadiazoles gave 1,3,4-thiadiazole-2-diazonium sulfates which were converted to 2-azido-1,3,4-thiadiazoles. The latter reacted with ethyl acetoacetate in the presence of sodium methoxide in methanol to produce 1-(5-R¹-1,3,4-thiadiazol-2-yl)-5-R²-1H-1,2,3-triazole-4-carboxylic acid derivatives. The reactions of 2-azido-5-methyl-1,3,4-thiadiazole and 2-azido-1,3-thiazole with ethyl 3-(1,3-benzodioxol-5-yl)-3-oxopropanoate led to the formation of 1,2,3-triazole ring under milder conditions (K₂CO₃, DMSO). Various 1,2,3-triazole-4-carboxylic acid derivatives were synthesized.     

5-(4,6-Diphenyl-2-pyrimidinyl)-1,3,4-oxadiazole-2-thione with Some C-Electrophiles and N-Nucleophiles

5-(4,6-Diphenyl-2-pyrimidinyl)-1,3,4-oxadiazole-2-thione reacted with haloalkanes or their derivatives containing side chain oxo group to give S-alkylated compounds. Aminomethylation and acylation of the thione yielded N₍₃₎-derivatives. Treatment of the title compound with hydrazine hydrate in butanol resulted in 4-amino-5-(4,6-diphenyl-2-pyrimidinyl)-1,2,4-triazole-3-thione via a recyclization reaction. Reaction of the title compound with hydrazine hydrate or phenylhydrazine in dioxane led to formation of the corresponding thiocarbohydrazides. The latter in the presence of a base were cyclized to 4-amino-1,2,4-triazole-3-thiones.     

Synthesis and transformations of 3-acetylpyridine-2(1<Emphasis Type="Italic">H</Emphasis>)-thiones

Reactions of substituted 3-cyanopyridine-2(1H)-thiones with methyllithium gave 3-acetylpyridine-2(1H)-thiones. The best results were achieved by adding a solid-state thione to a solution of methyllithium in ether (thione: MeLi = 1: 3). The compounds obtained and their 3-pentanoyl analogs were used to synthesize a number of fused heterocyclic systems. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1504–1507, July, 2008.     

Reaktion von Phenyldiazomethan mit 1,3-Thiazol-5(4H)-thionen: Basenkatalysierte Ring-Öffnung des Primäradduktes

Reaction of Phenyldiazomethane with 1,3-Thiazole-5(4H)-thiones: Base-Catalyzed Ring Opening of the Primary Adduct Reaction of 1,3-thiazole-5(4H)-thiones 1 and phenyldiazomethane ( 2a ) in toluene at room temperature yields the thiiranes trans- and cis-1,4-dithia-6-azaspiro[2.4]hept-5-enes (trans- and cis- 4 ; Scheme 2). With Ph₃P in THF at 70°, these thiiranes are transformed stereospecifically into (E)- and (Z)-5-benzylidene-4,5-dihydro-1,3-thiazoles 5 , respectively. In the presence of DBU, 1 and 2a react to give 1,3,4-thiadiazole derivatives 6 or 7 via base-catalyzed ring opening of the primary cycloadduct (Scheme 3). In the case of 2-(alkylthio)-substituted 1,3-thiazole-5(4H)-thiones 1c and 1d , this ring opening proceeds by elimination of the corresponding alkylthiolate, yielding isothiocyanate 7 . The structures of (Z)- 5c and 6b have been established by X-ray crystallography.     

A simple and efficient approach for the synthesis of a novel class aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives via intramolecular nucleophilic substitution reaction

In this study, we synthesized a new series of substituted aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives (6-24) in yields ranging from 42 to 70% with an interesting mechanism that involves internal nucleophilic substitution followed by an S_N2-type nucleophilic substitution. First, 1-(4-chlorophenyl)-2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethanone (3) was synthesized from the reaction of 5-methyl-1,3,4-thiadiazole-2-thiol (1) with 2-bromo-1-(4-chlorophenyl)ethanone (2) in the presence of potassium hydroxide. Then, 1-(4-chlorophenyl)-2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethanol (4) was synthesized by a reduction reaction of this compound using NaBH₄. Finally, 5-methyl-3-alkyl-1,3,4-thiadiazol-2(3H)-one derivatives (6-24), which are the target compounds, were synthesized from the reaction of this compound (4), which is a secondary alcohol with various alkyl halides (5a-n) in the presence of sodium hydride (NaH). This study presents an interesting reaction mechanism related to the synthesis of aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives that is not recorded in the literature.     

Reaction of 4-thioxo-1,3-benzothiazines with thiocarbohydrazine: Synthesis and reactivity of 1,3,4-triazolo[3,2-c]quinazoline derivatives

2-Aryl-4-thioxo-1,3-benzothiazines react with thiocarbohydrazide to give the new mesoionic compounds an-hydro 1-amino-5-aryl-2-mercapto-1,3,4-triazolo[3,2-c]quinazolin-4-ium hydroxides. These compounds react with methyl iodide, aldehydes and phenacyl bromides to give 1-amino-5-aryl-2-methylthio-1,3,4-triazolo-[3,2-c]quinazolin-4-ium iodides, 4-arylidenamino-3-(o-aroylamino)phenyl-1H-1,2,4-triazolin-5-thiones and 3-(o-aroylamino)phenyl-6-aryl-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines, respectively. These latter compounds by sequential treatment with methyl trifluoromethanesulphonate and triethylamine lead to 3-(o-aroylamino)-phenyl-6-aryl-1-methyl-7-mercapto-1H-pyrazolo[5,1-c]-1,2,4-triazoles.     

Synthesis and spectral properties of new hetarylazo indole dyes

A series of new hetarylazo indole dyes were synthesized by azo coupling of 2-phenyl-, 2-methyl-, and 1-methyl-1-phenyl-1H-indole with diazonium salts derived from 5-methylsulfanyl-1H-1,2,4-triazol-3-amine, 1H-1,2,4-triazol-3-amine, 5-methylisoxazol-3-amine, and 5-amino-1,3,4-thiadiazole-2-thiol. The dyes were characterized by the IR spectra, electronic absorption spectra in the UV and visible regions, and ¹H NMR and mass spectra. The effects of solvent nature, acidity of the medium, temperature, and concentration on the electronic absorption spectra in the visible region and the dependence of the color of the dyes on the nature of heterocyclic fragment were examined. Published in Russian in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 7, pp. 1041–1047. The text was submitted by the authors in English.     

ZnII and CuII complexes generated from 5‐(pyridin‐4‐yl)‐3‐[2‐(pyridin‐4‐yl)ethyl]‐1,3,4‐oxadiazole‐2(3H)‐thione

A new 1,3,4‐oxadiazole‐containing bispyridyl ligand, namely 5‐(pyridin‐4‐yl)‐3‐[2‐(pyridin‐4‐yl)ethyl]‐1,3,4‐oxadiazole‐2(3H)‐thione (L), has been used to create the novel complexes tetranitratobis{μ‐5‐(pyridin‐4‐yl)‐3‐[2‐(pyridin‐4‐yl)ethyl]‐1,3,4‐oxadiazole‐2(3H)‐thione}zinc(II), [Zn₂(NO₃)₄(C₁₄H₁₂N₄OS)₂], (I), and catena‐poly[[[dinitratocopper(II)]‐bis{μ‐5‐(pyridin‐4‐yl)‐3‐[2‐(pyridin‐4‐yl)ethyl]‐1,3,4‐oxadiazole‐2(3H)‐thione}] nitrate acetonitrile sesquisolvate dichloromethane sesquisolvate], {[Cu(NO₃)(C₁₄H₁₂N₄OS)₂]NO₃·1.5CH₃CN·1.5CH₂Cl₂}_n, (II). Compound (I) presents a distorted rectangular centrosymmetric Zn₂L₂ ring (dimensions 9.56 × 7.06 Å), where each Zn^II centre lies in a {ZnN₂O₄} coordination environment. These binuclear zinc metallocycles are linked into a two‐dimensional network through nonclassical C—H...O hydrogen bonds. The resulting sheets lie parallel to the ac plane. Compound (II), which crystallizes as a nonmerohedral twin, is a coordination polymer with double chains of Cu^II centres linked by bridging L ligands, propagating parallel to the crystallographic a axis. The Cu^II centres adopt a distorted square‐pyramidal CuN₄O coordination environment with apical O atoms. The chains in (II) are interlinked via two kinds of π–π stacking interactions along [01]. In addition, the structure of (II) contains channels parallel to the crystallographic a direction. The guest components in these channels consist of dichloromethane and acetonitrile solvent molecules and uncoordinated nitrate anions.     

A new method for the synthesis of 6H,11H-indolo[3,2-c]-isoquinolin-5-ones/thiones and their reactions

The synthesis of 8-substituted and unsubstituted 6H,11H-indolo[3,2-c]isoquinolin-5-ones/thiones 3a-c and 4a-c and their derivatives viz, ethyl (8-substituted-6H,11H-indolo[3,2-c]isoquinolin-5-on-6-yl)acetates 5a-c , (8-substituted-6H,11H-indolo[3,2-c]isoquinolin-5-on-6-yl)acetyl hydrazides 6a-c , 3,5-disubstituted-pyrazoles 7a-c and 8a-c , 3-substituted-pyrazol-5-ones 9a-c and 5-(8-substituted-6H,11H-indolo[3,2-c]isoquinolin-5-on-6-yl)methyl-1,3,4-oxadiazole-2-thiones 10a-c , also ethyl (8-substituted-11H-indolo[3,2-c]isoquinolin-5-ylthio)ace-tates 11a-c , (8-substituted-11Hindolo[3,2-c]isoquinolin-5-ylthio)acetyl hydrazides 12a-c , 3,5-disubstituted-pyrazoles 13a-c and 14a-c , 3-substituted-pyrazol-5-ones 15a-c and 5-(8-substituted-11H-indolo[3,2-c]isoquin-olin-5-yl)thiomethyl-1,3,4-oxadiazole-2-thiones 16a-c is described.     

Synthesis of 3,5-disubstituted 1,3,4-oxadiazole-2-thiones as potential fungicidal agents

Sixteen new 3-arylaminomethyl-5-(2,4-dichlorophenyl)-1,3,4-oxadiazole-2-thione and six 3-alkyl aryl alkyl-5-(2,4-dichlorophenyl)-1,3,4-oxadiazole-2-thiones were synthesised and characterised by their sharp melting points, elemental analysis, ir, ¹H nmr and mass spectra. These substituted oxadiazolethiones were screened for their fungitoxic properties. Most of the compounds showed toxicity against two test organisms, Curvularia verruciformis and Alternaria tenuis. The degree of inhibition ranged from 38--100% for a few compounds.     

On the possibility for synthesizing dihydrotriazolothiadiazoles by condensation of 4-amino-2,4-dihydro-3<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazole-3-thiones with aromatic aldehydes

Regardless of the conditions, the condensation of 4-amino-2,4-dihydro-3H-1,2,4-triazole-3-thiones with aromatic aldehydes afforded the corresponding hydrazones as the only product. Both initial amines and resulting hydrazones exist as the thione rather than thiol tautomer. In no case bicyclic 5,6-dihydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles that are isomeric to the hydrazones were detected. DFT quantum chemical calculations at the B3LYP/6-31+g(d,p) level of theory with full geometry optimization showed that the hydrazone structure in methanol and DMF is more stable than the bicyclic isomer by 19–23 kcal/mol, which completely excluded the possibility for such cyclization. The thione tautomer of the hydrazones is more stable than the thiol structure by 11–13 kcal/mol.     

On Triazoles. XXXII. The reaction of 5-amino-1 H-1,2,4-triazolylcarbothiohydrazides with β- and γ-oxo-esters

5-Amino-lH-1,2,4-triazolylcarbothiohydrazides gave β and γ-oxo-esters in boiling ethanol [1,2,4]triazolo- [1,5-d][1,2,4,6]tetrazepine-5-thiones 3 . Analogously ethyl 2-oxocyclohexanecarboxylate provided a mixture of two diastereomeric spiro derivatives 5 and 6 . At 130°, 2-acetonyl-5-methyl-4,5-dihydro-1,3,4-oxadiazole-5-thione ( 8 ) was formed. Ring closure of 3e (R¹ = CH₃, R² = CH₂CH₂COOEt, Q = morpholino) lead to the isomeric pyrrolo[2,1-g][1,2,4]triazolo[1,5-d][1,2,4,6]tetrazepin-8(11H)-one ( 12 ) and pyrrolo[1,2-f][1,2,4]triazolo-[1,5-d][1,2,4,6]tetrazepin-10(7H)-one ( 13 ) derivatives representing two new ring systems.     

Umsetzung von Diazoessigsäure-ethylester mit 1,3-Thiazol-5(4H)-thionen

Reaction of Ethyl Diazoacetate with 1,3-Thiazole-5(4H)-thiones Reaction of ethyl diazoacetate ( 2a ) and 1,3-thiazole-5(4H)-thiones 1a,b in Et₂O at room temperature leads to a complex mixture of the products 5–9 (Scheme 2). Without solvent, 1a and 2a react to give 10a in addition to 5a–9a . In Et₂O in the presence of aniline, reaction of 1a,b with 2a affords the ethyl 1,3,4-thiadiazole-2-carboxylate 10a and 10b , respectively, as major products. The structures of the unexpected products 6a, 7a , and 10a have been established by X-ray crystallography. Ethyl 4H-1,3-thiazine-carboxylate 8b was transformed into ethyl 7H-thieno[2,3-e][1,3]thiazine-carboxylate 11 (Scheme 3) by treatment with aqueous NaOH or during chromatography. The structure of the latter has also been established by X-ray crystallography. In the presence of thiols and alcohols, the reaction of 1a and 2a yields mainly adducts of type 12 (Scheme 4), compounds 5a,7a , and 9a being by-products (Table 1). Reaction mechanisms for the formation of the isolated products are delineated in Schemes 4–7: the primary cycloadduct 3 of the diazo compound and the C?S bond of 1 undergoes a base-catalyzed ring opening of the 1,3-thiazole-ring to give 10 . In the absence of a base, elimination of N₂ yields the thiocarbonyl ylide A ′, which is trapped by nucleophiles to give 12 . Trapping of A ′, by H₂O yields 1,3-thiazole-5(4H)-one 9 and ethyl mercaptoacetate, which is also a trapping agent for A ′, yielding the diester 7 . The formation of products 6 and 8 can be explained again via trapping of thiocarbonyl ylide A ′, either by thiirane C (Scheme 6) or by 2a (Scheme 7). The latter adduct F yields 8 via a Demjanoff-Tiffeneau-type ring expansion of a 1,3-thiazole to give the 1,3-thiazine.     

Umsetzung von Di(tert-butyl)- und Diphenyldiazomethan mit 1,3-Thiazol-5(4H)-thionen: Isolierung und Kristallstruktur des primären Cycloadduktes

Reaction of Di(tert-butyl)- and Diphenyldiazomethane and 1,3-Thiazole-5(4H)-thiones: Isolation and Crystal Structure of the Primary Cycloadduct Reactions of diazo compounds with C?S bonds proceed via the formation of thiocarbonyl ylides, which, under the reaction conditions, undergo either 1,3-dipolar cycloadditions or electrocyclic ring closer to thiiranes (Scheme 1). With the sterically hindered di(tert-butyl)diazomethane ( 2c ), 1,3-thiazole-5(4H)-thiones 1 react to give spirocyclic 2,5-dihydro-1,3,4-thiadiazoles 3 (Scheme 2). These adducts are stable in solution at ?20°, and they could be isolated in crystalline form. The structure of 3c was established by X-ray crystallography. In CDCl₃ solution at room temperature, a cycloreversion occurs, and the adducts of type 3 are in an equilibrium with 1 and 2c . In contrast, the reaction of 1 with diphenyldiazomethane ( 2d ) gave spirocyclic thiiranes 4 as the only product in high yield (Scheme 3). The crystal structure of 4b was also determined by X-ray analysis. The desulfurization of compounds 4 to 4,5-dihydro-5-(diphenylmethylidene)-1,3-thiazoles 5 was achieved by treating 4 with triphenylphosphine in boiling THF. The crystal structure of 5f is shown.     

Synthesis of 5-(aroylamino)-2-methyl-2H,-1,2,4-thiadiazol-3-ones by oxidative cyclization of 1-aroyl-5-methyl-2-thiobiurets

5-Aroylamino-2-methyl-2H-1,2,4-thiadiazol-3-ones 3 have been synthesized by oxidative cyclization of 1-aroyl-5-methyl-2-thiobiurets 2 with hydrogen peroxide in an alkaline solution. The needed 1-aroyl-5-methyl-2-thiobiurets 2 have been obtained through the addition of methylurea to the corresponding aroyl isothiocyanates.     

5-Aryl-1,3,4-oxadiazoline-2(3H)-thiones in reactions with alkyl haloacetates

The reaction of 5-aryl-1,3,4-oxadiazoline-2(3H)-thiones with alkyl haloacetates has been studied. It was shown that the reaction proceeds to give S-substituted products. The effect of the nature of the substituents in the molecules of both the thiones and the haloacetates on the reaction route and yields has been examined.