Oxidation of vinyl derivatives of benzimidazole-2-thione

N-Vinylbenzimidazole-2-sulfonic acid, 2-benzimidazolyl vinyl sulfoxide, and 2-benzimidazolyl vinyl sulfone were obtained in high yields by the action of concentrated hydrogen peroxide and acetyl hydroperoxide on N- and S-monovinyl derivatives of benzimidazole-2-thione. N-Vinyl-2-benzimidazolone and a complex mixture of polymeric products are formed in the oxidation of N,S-divinyl-2-mercaptobenzimidazole. It is shown that the reactivity of the sulfur atom depends on the number of vinyl groups and their orientation with respect to the heteroatoms.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1670–1673, December, 1975.     

Bromination of vinyl derivatives of benzimidazole-2-thione

The reaction of vinyl derivatives of benzimidazole-2-thione with bromine was investigated. It is shown that the principal reaction is the addition of the halogen to the double bond of the vinyl group. Depending on the structure of the starting vinyl derivative, elimination of hydrogen bromide or halogenation at the heteroring nitrogen atom, which leads to the formation of hydrohalides, is subsequently possible.Translated, from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1092–1094, August, 1982.     

Cyanoacetylenes in a reaction with benzoxazole-2-thione and benzoxazol-2-one

The reaction of benzoxazole-2-thione and benzoxazol-2-one with substituted cyanoacetylenes was studied. 2-[(3-Phenyl-2-propenenitrile)thio]benzoxazole was obtained by the reaction of benzoxazole-2-thione with phenylcyanoacetylene. Benzoxazol-2-one with phenylcyanoacetylene and a tertiary cyanoacetylenic alcohol gave the corresponding N-adducts.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1390–1391, June, 1990.     

Synthesis and NMR spectroscopic assignment of chlorinated benzimidazole-2-thione derivatives

The benzimidazole-2-thione scaffold is present in many drugs encompassing various therapeutic areas. Due to the broad spectrum of bioactivities it also represents an important starting point in drug discovery campaigns, especially those based on fragment-based design. Despite simple structures the tautomerism and regioisomerism of substituted benzimidazole-2-thiones makes unambiguous structural analysis difficult. Tautomeric duplicates are present in commercial libraries resulting in two tautomers being sold as different products. To showcase an example of appropriate structural determination, we synthesized and characterized a set of benzimidazole-2-thiones with different positions of a chlorine atom on the ring. Using NOESY and ¹³C NMR spectroscopy, we determined that the thione tautomer predominates in the thione-thiol equilibrium. Furthermore, NOESY and HMBC experiments confirmed the position of the substituents on the benzimidazole-2-thione ring.     

Kinetics and mechanism of hydrolysis of N-acyloxymethyl derivatives of azetidin-2-one

The pH-independent, acid-catalyzed and base-catalyzed hydrolyses of N-acyloxymethylazetidin-2-ones all occur at the ester function. The pH-independent hydrolysis involves rate-limiting alkyl C-O fission and formation of an exocyclic beta-lactam iminum ion. This iminium ion is then trapped by water at the exocyclic iminium carbon atom, rather than at the beta-lactam carbonyl carbon atom, to form the corresponding N-hydroxymethylazetidin-2-ones. Calculations carried out at the B3LYP/6-31+G(d) level of theory also support that nucleophilic attack by water takes place at the exocyclic carbon rather than at the beta-lactam carbonyl carbon of the iminium ion. The mechanism for the acid-catalyzed pathway involves a preequilibrium protonation, probably at the beta-lactam nitrogen, followed by rate-limiting alkyl C-O fission with formation of an exocyclic iminum ion. The base-catalyzed hydrolysis involves rate-limiting hydroxide attack at the ester carbonyl carbon. These results imply formation of a beta-lactam system containing a positively charged amide nitrogen atom that hydrolyzes via a pathway that preserves the beta-lactam structure in the product and provide further evidence that cleavage of the beta-lactam C-N bond is not as facile as is commonly imagined.     

A facile and efficient procedure for the synthesis of new benzimidazole-2-thione derivatives

A series of benzimidazole-2-thione derivatives was synthesized using a reaction between the macrocyclic aminal 16H,13H-5:12,7:14-dimethanedibenzo[d,i]-[1,3,6,8] tetraazecine (DMDBTA, 5) and various nucleophiles in the presence of carbon disulfide. A full chemical characterization using IR, 1H-, 13C-NMR and GC-MS analyses of the new compounds is provided. These compounds were separated from the reaction mixture by column chromatography (CC) in highly pure form in 15%-51.4% yield.     

Reaction of benzimidazole-2-thione with cyanoacetylene alcohols

Conclusions 2-Iminobenzimidazo-1,3-thiazines containing a hydroxyl group were obtained by the reaction of benzimid-azole-2-thione with tertiary cyanoacetylene alcohols. It was observed that they have enhanced stability toward alkalis.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, pp. 1903–1904, August, 1984.     

Synthesis and spatial structure of 1-(cytisin-1-ylmethyl)benzimidazole-2-thione

New derivatives of cytisine and anabasine alkaloids containing benzothiazole and benzimidazole fragments were discussed. Physicochemical characteristics of the new compounds were determined. The structure of 1-(cytisin-1-yl-methyl)benzimidazole-2-thione was studied by X-ray diffraction analysis.     

Acylation of purine-8-thione and benzimidazole-2-thione: A reinvestigation of the site of acylation

Purine-8-thione ( 1 ) is acylated on nitrogen, not on sulfur as was previously reported. Thus, the reactions of 1 with ethyl chloroformate and with acetic anhydride yield, respectively, ethyl purine-8-thione-9( 7 )-carboxylate ( 3 ) and 9 ( 7 )acetylpurine-8-thione ( 7 ) as shown by independent synthesis and spectra. In like manner, benzimidazole-2-thione ( 10 ) reacts with acetic anhydride, ethyl chloroformate, benzoyl chloride, and cyclohexyl isocyanate to yield the corresponding N-acylated derivatives. In addition, 10 yields 1,3-dibenzoylbenzimidazole-2-thione on treatment with 2 equivalents of benzoyl chloride.     

Interaction of benzimidazole-2-thione with propargyl bromide and 1,3-dibromopropyne

Interaction of benzimidazole-2-thione with propargyl bromide under found conditions permitted the direct synthesis of 2-(2-propynylsulfanyl)-3H-1,3-benzimidazolium bromide, the base 2-(2-propynylsulfanyl)-1H-1,3-benzimidazole, stable crystalline 2-(1,2-propadienylsulfanyl)-1H-1,3-benzimidazole, and 3-methyl[1,3]thiazolo[3,2-a][1,3]benzimidazole. The reaction of benzimidazole-2-thione with 1,3-dibromopropyne in chloroform or absolute methanol gave 2-(3-bromo-2-propynylsulfanyl)-3H-1,3-benzimidazolium bromide, and in absolute methanole in the presence of a twofold excess of sodium methoxide the reaction proceeded stereo-and regioselectively to give 3-[(Z)-bromomethylidene][1,3]thiazolo[3,2-a][1,3]benzimidazole. Presented to Academician B. A. Trofimov on his 70^th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, 1399–1405, September, 2008.     

Radical addition of thiols to vinyl derivatives of 4,5-diphenylimidazole-2-thione

It is shown that 2-vinylthio- and 1-vinyl-2-vinylthio-4,5-diphenylimidazoles readily add thiols to the double bond of the vinyl group attached to the sulfur atom. A vinyl group attached to the nitrogen atom undergoes only 7–15% thiylation; this is explained by the electron-acceptor effect of phenyl groups and also by steric factors.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1554–1556, November, 1976.     

Recyclization of 4,5-diphenyloxazolin-2-one and -2-thione under the influence of amines

4,5-Diphenyl-4-oxazolin-2-one and -2-thione undergo recyclization to 1-substituted 4,5-diphenyl-4-imidazolin-2-ones and -2-thiones, respectively, under the influence of primary amines. The action of hydrazine hydrate on the oxazolone leads to 5,6-diphenyl-1,2,3,4-tetrahydro-1,2,4-triazin-3-one. The corresponding ureas were isolated from the reaction mixtures in a number of cases.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1028–1030, August, 1981.     

Reaction of benzimidazole-2-thione with 1,2-dibromoethane. Coronand synthesis

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, p. 136, January, 1990.     

Vibrational spectra of imidazoline-2-thione and imidazoline-2-one

Raman and infrared spectra of imidazoline-2-thione (IMZT) and imidazoline-2-one (IMZO) have been recorded. Normal coordinate analyses have been performed for all the fundamental vibrations of IMZT, IMZT-d₂ and IMZO employing a Urey—Bradley potential function supplemented with valence type force constants for the out of plane modes. The results of the vibrational analyses are discussed in relation to the assignments in related molecules. The vibrational assignments for IMZT and IMZO have been compared with those in structurally similar molecules and the need to obtain more reliable band assignments for some of the molecules considered is emphasised.     

Comparison of oxygen and sulfur effects on keto-enol chemistry in benzolactone systems: benzo[b]-2,3-dihydrofuran-2-one and -2-thione and benzo[b]-2,3-dihydrothiophene-2-one and -2-thione

Carbon-acid ionization constants, Q(K)(a)(concentration quotient at ionic strength = 0.10 M), were determined by spectrophotometric titration in aqueous solution for benzo[b]-2,3-dihydrofuran-2-one (3, pQ(K)(a) = 11.87), benzo[b]-2,3-dihydrothiophene-2-one (2, pQ(K)(a) = 8.85), and benzo[b]-2,3-dihydrofuran-2-thione (1, pQ(K)(a) = 2.81). Rates of approach to keto-enol equilibrium were also measured for the latter two substrates in perchloric acid, sodium hydroxide, and buffer solutions, and the rate profiles constructed from these data gave the ionization constants of the enols ionizing as oxygen or sulfur acids pQ(E)(a) = 5.23 for 2 and pQ(E)(a) = 2.69 for 1. Combination of these acidity constants with the carbon-acid ionization constants according to the relationship Q(K)(a)/Q(E)(a) = K(E) then gave the keto-enol equilibrium constants pK(E) = 3.62 for 2 and pK(E) = 0.12 for 1. The fourth, all-sulfur, member of this series, benzo[b]-2,3-dihydrothiophene-2-thione (4), proved to exist solely as the enol in aqueous solution, and only the enol ionization constant pQ(E)(a) = 3.44 could be determined for this substance; the limits pK(E) < 1.3 and pQ(K)(a) < 2.1, however, could be set. The unusually high acidities and enol contents of these substances are discussed, as are also the relative values of the ketonization and enolization rate constants measured; in the latter cases, Marcus rate theory is used to determine intrinsic kinetic reactivities, free of thermodynamic effects.     

Solvatochromism of 3-[2-(aryl)benzoxazol-5-yl]alanine derivatives

The photophysical properties of N-Boc-3-[2-(9-anthryl)benzoxazol-5-yl]-l-alanine methyl ester (BoxAnt) and N-Boc-3-[2-[4-(9′-(10′-butyl)anthryl)phenyl]benzoxazol-5-yl]-l-alanine methyl ester (BoxPhAnt) were studied in a series of solvents. Their absorption spectra are less sensitive to the solvent polarity than the corresponding fluorescence spectra which show a pronounced solvatochromic effect leading to large Stokes shifts. Using an efficient solvatochromic method, based on the empirical solvent polarity parameter , a large change of the dipole moment on excitation for BoxPhAnt has been found. From an analysis of the solvatochromic behaviour of the absorption and fluorescence spectra in terms of bulk solvent polarity functions, f(_r, n) and g(n), a larger excited-state dipole moment (about 8 D, ψ = 56) was obtained for BoxPhAnt than for BoxAnt (about 3 D, ψ = 0). Both applied methods gave similar values of the excited-state dipole moments for both compounds studied.     

Kinetics of the hydrolysis of mixed cellulose derivatives

By acetylating weakly substituted Na and H carboxymethylcelluloses and methylcellulose we have synthesized acetone-soluble highly substituted mixed derivatives of cellulose — acetocarboxymethylcellulose and acetomethylcellulose. Water-soluble products have been obtained from these esters by subsequent deep hydrolysis. The kinetics of the hydrolysis of the acetyl groups in the mixed derivatives obtained have been studied. Rate constants of the hydrolysis reactions have been calculated. The influence of the substituted groups on the acetylation and hydrolysis reactions has been determined.Tashkent Institute of Chemical Technology. Translated from Khimiya Prirodnykh Soedinenii, Vol. 33, No. 1, pp. 102–106, January–February, 1997.