Cycloaddition-elimination reactions of 4-methyl-5-phenylimino-Δ2-1,2,3,4-thiatriazoline with electrophilic nitriles

4-Methyl-5-phenyliminothiatriazoline 4 undergoes two consecutive cycloaddition-elimination reactions with ethyl cyanoformate and p-toluenesulfonyl cyanide in refluxing chloroform, and yields the 1,2,4-thiadiazolines 6a,b via the isomers 5a,b . In acetone as the solvent, the reactions occur at room temperature, due to the formation of the 1,2,4-oxathiazolidine 12 as the intermediate. When trichloroacetonitrile was used, only the decomposition products of 4 , namely 7 and 8 were obtained.     

Mechanism of the cycloaddition-elimination reactions of 4-methyl-5-phenylimino-δ2-1,2,3,4-thiatriazoline with alkyl and aryl isothiocyanates

The formation of thiadiazolidines 3a-c and dithiazolidines 4a-c and 5a-b from the title reactions has been studied in detail under a variety of conditions. On the basis of kinetic measurements, isomerization studies and cross experiments a mechanism is proposed involving path (b) (Scheme 1) as the first step, followed by a series of isomerizations as shown in Scheme 3 .     

Cycloaddition-elimination reactions of 4-methyl-5-(substituted)-imino-Δ2-1,2,3,4-thiatriazolines with isocyanates

4-Methyl-5-(substituted)imino-1,2,3,4-thiatriazolines 1 (R² ≠ Me) undergo cycloaddition-elimination reactions with isocyanates to yield 4-methyl-5-(substituted)imino-1,2,4-thiadiazolidine-3-ones 5 via the thermodynamically less stable isomers 4 . The latter have not been isolated, except for 4q which was shown to iso-merize rapidly into 5q with phenylsulfonyl isocyanate. The reactions of 1 are accelerated by using less bulky R² substituents and more electrophilic isocyanates, in accordance with the viewpoint that 1 reacts as a masked 1,3-dipole. The products 4i-n (= 5i-n ), derived from 1b , add isocyanates reversibly to give 2,3,4,5-tetrahydro-6aλ⁴-thia-1,3,4,6-tetraazapentalene-2,5-diones 9i-n , which have been isolated and characterized spectroscopically. Such compounds with a hypervalent sulfur atom thus occur as intermediates during the isomerization of 4 to 5 under the influence of isocyanates.     

On the mechanism of thermal decomposition of 4-alkyl-5-sulfonylimino-Δ2-1,2,3,4-thiatriazolines

The kinetics of the thermal decomposition of several sulfonyl substituted thiatriazolinimines 1a-g were investigated in different solvents both in the presence and in the absence of trapping reagents. The first-order rate constants observed in all cases, are dependent on the inductive effect of the sulfonyl substituent (R), as well as on solvent polarity, but independent on the nature and concentration of the co-reagent. These results, and the low activation energy, are rationalized by assuming an anchimeric assistance of the sulfonyl group during thermolysis. This would give the intermediate 7 , which collapses to the thiaziridinimine 2 before being trapped by the co-reagent.     

Palladium(II) complexes with 5-methyl-5-(4-pyridyl)-2,4-imidazolidenedione

Two new palladium(II) complexes with 5-methyl-5-(4-pyridyl)-2,4-imidazolidenedione(mpyh) were synthesized: cis-[Pd(mpyh)₂Cl₂]·H₂O and cis-[Pd(mpyh)₂Br₂]·2H₂O. The molecular formulae of the complexes were confirmed by elemental analysis, IR, ¹H NMR spectra and DTA study. The ligand is coordinated to the palladium ion with N-atom of the pyridine ring. The spectroscopic data indicate a square planar geometry with two N-pyridine atoms and two halogene anions in cis position. The final product of the thermal decomposition of cis-[Pd(mpyh)₂Cl₂]·H₂O is metallic Pd, whereas for cis-[Pd(mpyh)₂Br₂]·2H₂O the residue consists of metallic Pd and C. The cytotoxic effects of the complexes were examined in vitro on some human tumor cell lines. The cis-[Pd(mpyh)₂Cl₂]·H₂O proved to be more active as compared to the cis-[Pd(mpyh)₂Br₂]·2H₂O.     

Reactions of 3-methyl-1-(2-pyridyl)-4-chloro-5-formyl-6,7-dihydroindazole

The reactions of 3-methyl-1-(2-pyridyl)-, 3-methyl-1-phenyl-, and 3-methyl-1,6-diphenyl-4-chloro-5-formyl-6,7-dihydroindazoles with guanidine and benzo- and 3- and 4-pyridinecarbamidines gave the corresponding 8-substituted 1-methyl-3-(2-pyridyl)-and 1-methyl-3-phenyl-4,5-dihydropyrazolo[5,4-h]quinazolines. With acetic anhydride the same indazole derivatives gave the 4-acetoxy-5-formyl derivatives, and with hydroxylamine they gave4-chloro-5-hydroxyiminomethyl-6,7-dihydroindazoles. Thereactionof4-acetoxyl-1-(2-pyridyl)-5-formyl-6,7-dihydroindazole with hydroxylamine gave 8-methyl-6-(2-pyridyl)-4,5-dihydroisoxazolo[5,4-e]indazole, while dehydration of 5-hydroxyiminomethyl-3-methyl-4-chloro-6,7-dihydroindazole gave the 4-chloro-5-cyano derivative. The reaction of the latter with nucleophilic reagents was investigated.Riga Technical University, Riga, Latvia LV-1658. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1209–1213, September, 1998.     

Spectrophotometric determination of mercury with 5-(6-methyl-2-pyridyl)methylene-2-thiohydantoin

A method is described for the direct spectrophotometric determination of mercury(II) with 5-(6-methyl-2-pyridyl)methylene-2-thiohydantoin. The influence of the different experimental parameters on the formation of the complex were studied and optimum conditions for the determination of mercury were established. The precision of the procedure, expressed in terms of relative standard deviation, was 0.2%. Two different complexes (1:2 and 1:1 cation-reagent stoichiometries) have been detected. The method has been tested on copper amalgam for dental use.     

Synthesis and reactions of 1-(2-pyridyl)-3-methyl-4-chloro-5-formyl-6,7-dihydroindazoles

The Vilsmeier formylation of 1-(2-pyridyl)-3-methyl-4-oxo-4,5,6,7-tetrahydroindazole and its 6-phenyl derivative gives 1-(2-pyridyl)-3-methyl-4-chloro-5-formyl-6,7-dihydroindazoles. Reactions of these derivatives with different N- and C-nucleophilic agents, including bisnucleophiles, were studied as a means of obtaining new 4- and 5-functional derivatives of indazole and its condensed systems.Riga Technical University, Riga LV-1658, Latvia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 768–773, June, 1998.     

Basicities of thiazole heterocyclic compounds and the reaction of 3-methyl-2-methylimino-Δ4-thiazolines with ethyl bromoacetate and 2-bromoacetophenone

The pK_a′s of several thiazole heterocyclic compounds have been determined and represent products with significantly high values. Because of their high basicities, sometimes these compounds were able to act as not only nucleophiles but also strong organic bases. 4-Substituted-3-methyl-2-methylimino-Δ⁴-thiazolines 5a-d reacted with ethyl bromoacetate in refluxing benzene, giving the corresponding N-alkylated salts 8a-d , while the products obtained from the reaction with 2-bromoacetophenone in the presence of base were pyrrolothiazines 10b-d.     

New approach to the formation of azepine ring: Synthesis of 2-methyl-6-(5-methyl-2-thienyl)-3H-azepine from 2-methyl-5-propargylthiophene and isothiocyanate

The first representative of thienyl-substituted 3H-azepines has been synthesized starting from dilithiated 2-methyl-5-propargylthiophene and isopropyl isothiocyanate. It was shown that N-(1-methylethylidene)-2-(5-methyl-2-thienyl)-1-(methylthio)-1,3-butadiene-1-amine (2-aza-1,3,5-triene) formed as a result of this reaction is readily converted into 2-methyl-6-(5-methyl-2-thienyl)-3H-azepine under the action of super bases. Dedicated to Academician B. A. Trofimov of the Russian Academy of Sciences on his 70^th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1380–1383, September, 2008.     

Synthesis and properties of N-methylmorpholinium 6-methyl-4-(4-pyridyl)-5-phenylcarbamoyl-3-cyano-1,4-dihydropyridine-2-thiolate

Condensation of acetoacetic acid anilide, 4-pyridyl aldehyde, cyanothioacetamide and N-methylmorpholine gave N-methylmorpholinium 6-methyl-4-(4-pyridyl)-5-phenylcarbamoyl-3-cyano-1,4-dihydropyridine-2-thiolate from which were obtained the corresponding substituted pyridinethiones, 2-alkylthio-1,4-dihydropyridines and 3-amino-2-benzoyl-6-methyl-4-(4-pyridyl)-5-phenylcarbamoylthieno[2,3-b]pyridine.T. G. Shevchenko Lugansk Pedagogical Institute, Lugansk 348011. N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 672–675, May, 1997.     

A facile synthesis of 2-substituted-4-(substituted)phenyl-Δ2-1,3,4-oxadiazolin-5-ones

The title compounds, 3, are formed at ambient temperature from 4,4-dimethyl-2-(substituted)-phenylsemicarbazides (1) and carboxylic acid chlorides in the presence of triethylamine. 2-Dimethylamino-4-(substiluted)phenyl-Δ²-1,3,4-oxadiazolin-5-ones are formed from 1 and dialkyl-carbamoyl chlorides at elevated temperature (about 15° ). Acylation of 1 with carboxylic acid anhydrides, also at elevated temperature, is accompanied by loss of dimethylamine from the intermediate l-acyl-4,4-dimethyl-2-(substituted)phenylsemicarbazides, 2, to give 3.     

Crystal and molecular structure of Δ-5,6-diphenyl-5-methoxy-1,2,4-triazacyclohexene-3-thione and Δ-4-methyl-5,6-diphenyl-5-ethoxy-1,2,4-triazacyclohexene-3-thione

Condensation of thiosemicarbazide or N(4)-ethylthiosemicarbazide with 1,2,8,9-tetraphenyl-3,7-diazanona-1,9-dione in the presence of copper(II) acetate in 96% ethanol leads to Δ⁶-5,6-diphenyl-5-methoxy-1,2,4-triazacyclohexene-3-thione, C₁₆H₁₅N₃OS, or Δ⁶-4-methyl-5,6-diphenyl-5-ethoxy-1,2,4-triazacyclohexene-3-thione, C₁₈H₁₉N₃OS. For C₁₆H₁₅N₃OS the crystal data are monoclinic, P2₁/c, a=9.7780(7), b=8.5120(3), c=18.2210(13) Å, β=100.958(3)°, V=1488.89(16) ų, and Z=4 in agreement with an earlier report. For C₁₈H₁₉N₃OS the crystal data are orthorhombic, P2₁2₁2₁, a=8.6940(3), b=12.9946(3), c=15.5139(5) Å, V=1752.68(9) ų, and Z=4.     

Synthesis and conversions of 3-(4-amino-5-methyl-4H-1,2,4-triazol-3-ylmethylene)-2-oxo-1,2,3,4-tetrahydroquinoxaline

The reaction of the hydrazone 3a with hydrazine hydrate in DBU/ethanol conveniently gave 3-(4-amino-5-methyl-4H-1,2,4-triazol-3-ylmethylene)-2-oxo-1,2,3,4-tetrahydroquinoxaline 6 . The reactions of 6 with an equimolar and 2-fold molar amount of nitrous acid afforded 3-(α-hydroxyimino-4-amino-5-methyl-4H-1,2,4-triazol-3-ylmethyl)-2-oxo-1,2-dihydroquinoxaline 9 and 3-(α-hydroxyimino-5-methyl-2H-1,2,4-triazol-3-ylmethyl)-2-oxo-1,2-dihydroquinoxaline 10 , respectively, which were converted into the 3-heteroarylisoxazolo[4,5-b]quin-oxalines 13a,b and 11 , respectively. Compound 9 was also cyclized into the 8-quinoxalinyl-1,2,4-triazolo-[3,4-f][1,2,4]triazines 14a,b .     

Reactions of 2-Amino-4-methyl-6-(2-pyridyl)- and 2-Amino-4-methyl-6-phenyl-7,8-dihydroindazolo[4,5-d]thiazoles with Aldehydes

The reaction of 2-amino-4-methyl-6-(2-pyridyl)-7,8-dihydroindazolo[4,5-d]thiazole, obtained by treating 3-methyl-4-oxo-1-(2-pyridyl)-4,5,6,7-tetrahydroindazole with pyridinium bromide perbromide and then with thiourea, and 2-amino-4-methyl-6-phenyl-7,8-dihydroindazolo[4,5-d]thiazole with 4-bromo-, 4-fluoro-, 4-dimethylamino-, 4-methoxy-, 3,4-dimethoxy-, and 3,4-methylenedioxybenzaldehydes, furfural, pyridinecarbaldehyde, and thiophenecarbaldehyde gave the corresponding Schiff bases. The products of the condensation of these aminothiazoles with cinnamaldehyde, 1-(2-pyridyl)- and 4-chloro-1-(2,4-difluorophenyl)-5-formyl-3-methyl-6,7-dihydroindazoles, 2-formyl-dimedone, and 2-formyl-1,3-indanedione were also obtained.     

Synthesis of 2-alkyl(aryl,hetaryl)-4-methyl-1,2,3,4-tetrahydroquinolines

We have developed a preparative, three stage of synthesis of substituted 1,2,3,4-tetrahydroquinolines. Treatment of N-aryl-imines with allylmagnesium bormide gave N-aryl-N-alkenylamines which were cyclized to the tetrahydroquinolines. The configurations and conformations of the 4-methyl-1,2,3,4-tetra-hydroquinolines containing different 2- substituents have been determined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 73–78, January, 1994.