Synthesis,Properties, and Reactions of 5-Substituted Derivatives of 2,3-Diphenylquinoxaline [1]

Summary. Catalytic hydrogenation of 5-nitro-2,3-diphenylquinoxaline led to the corresponding amine which, in turn, afforded products of nucleophilic substitution on reaction with alkoxymethylene derivatives. Thermal cyclization of selected alkoxymethylene derivatives yielded substituted pyridoquinoxalines. The conditions for successful hydrolysis of ester, decarboxylation of the acid, following chlorination of pyridone and reductive removal of the chlorine atom from it to produce parental heterocycle 2,3-diphenyl-pyrido[2,3-f]quinoxaline were found. All of the tested products of the nucleophilic substitution showed no antibacterial activity.Dedicated to Prof. Dr. M. Uher on the occasion of his 65^th birthday     

Thiophen-sulfoxide

The synthesis of several 5-methylsulfinyl-2-thiophenaldehyde derivatives is described.

     

Characterization of the sulfhydryl-sensitive site in the enzyme responsible for hydrolysis of 2-arachidonoyl-glycerol in rat cerebellar membranes

We have previously reported that the endocannabinoid, 2-arachidonoyl-glycerol (2-AG), is hydrolyzed in rat cerebellar membranes by monoglyceride lipase (MGL)-like enzymatic activity. The present study shows that, like MGL, 2-AG-degrading enzymatic activity is sensitive to inhibition by sulfhydryl-specific reagents. Inhibition studies of this enzymatic activity by N-ethylmaleimide analogs revealed that analogs with bulky hydrophobic N-substitution were more potent inhibitors than hydrophilic or less bulky agents. Interestingly, the substrate analog N-arachidonylmaleimide was found to be the most potent inhibitor. A comparison model of MGL was constructed to get a view on the cysteine residues located near the binding site. These findings support our previous conclusion that the 2-AG-degrading enzymatic activity in rat cerebellar membranes corresponds to MGL or MGL-like enzyme and should facilitate further efforts to develop potent and more selective MGL inhibitors.     

An HPLC study of tinidazole hydrolysis

Summary The high-performance liquid chromatographic (HPLC) method herein described allows the simultaneous determination of the hydrolysis kinetics of tinidazole and the formation kinetics of the hydrolysis products. Tinidazole is easily hydrolysed under basic conditions at raised temperature. The rate varies with the pH and the temperature of the solution, and the decomposition follows apparent first-order kinetics. The Arrheinius equation can be used to describe the effect of temperature on the half-life.     

Improved syntheses of thieno[2,3-b]- and [3,2-b]-fused naphthyridines

The preparation of eight isomeric thieno[2,3-b]- and [3,2-b]-fused naphthyridines [1] was improved through the Pd(0) catalyzed cross-coupling of 3-formyl-4-iodopyridine, 2-formyl-3-iodopyridine, 3-bromo-4-formylpyridine and 2-bromo-3-formylpyridine with t-butyl N-(2-trimethylstannyl-3-thienyl)car-bamate and t-butyl N-(3-trimethylstanny-2-thienyl)carbamate.     

Pyridine-substituted hydroxythiophenes. V. Preparation of 5-(2-, 3-and 4-pyridyl)-2-hydroxythiophenes

5-(2-, 3- and 4-Pyridyl)-2-t-butoxythiophenes have been prepared in very good yields by Pd(0) catalyzed cross-coupling of the three isomeric bromopyridines with 5-trimethylstannyl-2-t-butoxythiophene derived from 2-bromothiophene via 2-t-butoxythiophene. Dealkylation of 5-(2-, 3- and 4-pyridyl)-2-t-but-oxythiophenes with boron trifluoride etherate in dichloromethane at room temperature led to predominant formation of rearranged products, 5-(2- and 3-pyridyl)-3-t-butyl-3-thiolene-2-ones, together with a small amount of 5-(2- and 3-pyridyl)-2-hydroxythiophenes as a mixture of two tautomeric keto forms in the case of the 2-pyridyl and the 3-pyridyl isomers, and exclusive formation of rearranged product in the case of the 4-pyridyl isomer. However, dealkylation of 2-methoxy-5-(2-, 3- and 4-pyridyl)thiophenes, prepared similarly to the 5-(2-, 3- and 4-pyridyl)-2-t-butoxythiophenes, with boron tribromide under the same reaction conditions as above resulted exclusively in the tautomeric mixture of 5-(2- and 3-pyridyl)-3-thiolene-2-ones and 5-(2- and 3-pyridyl)-4-thiolene-2-ones in the case of the 2-pyridyl and 3-pyridyl isomers. In the case of the 4-pyridyl isomer polymerization took place.     

Pyridine-substituted hydroxythiophenes. II. Alkylation of o-(2-, 3- and 4-pyridyl)-3-hydroxythiophenes: Regiospecific formation of o-pyridyl-3-alkoxythiophenes

The alkylation of o-(2-, 3- and 4-pyridyl)-3-hydroxythiophenes has been investigated. In the case of 4-(2-, 3- and 4-pyridyl)-3-hydroxythiophene systems, the soft alkylating reagent, methyl iodide, using sodium hydride as the base and dimethylimidazolidinone as the solvent, gave rise to a mixture of O-alkylated and O,C-dialkylated products in the proportions of 4.6–6.5 to 1. However, in the case of 2-(2-, 3- and 4-pyridyl)-3-hydroxythiophene systems, the same reaction conditions brought about exclusively O-alkylated compounds in yields of 45–53%. In both cases, the hard alkylating reagent, methyl p-toluenesulfonate, with the same base and solvent, only give O-alkylated compounds in yields of 51–77%. These latter conditions resulted in a good preparative route for the regiospecific formation of o-pyridyl-3-alkoxythiophenes by using ethyl 2-bromopro-pionate as well as methyl p-toluenesulfonate as alkylating reagents. The hydrolysis of the esters, derived from alkylation with ethyl 2-bromopropionate, has also been investigated.     

On the syntheses of 1,3-disubstituted dithieno[3,4-b:3′,2′-d]pyridines via halogen-metal exchange of 1,3-dibromodithieno[3,4-b:3′,2′-d]pyridine

Halogen-metal exchange of 1,3-dibromodithieno[3,4-b:3′,2′-d]pyridine with butyllithium under different conditions has been studied. Upon reaction with iodine, N,N-dimethylacetamide, N,N-dimethylformamide, dimethyl carbonate, dimethyl disulfide and thiuram disulfide, the 1,3-diiodo-, 1,3-diacetyl-, 1,3-diformyl-, 1,3-dicarbomethoxy, 1,3-di(thiomethyl)- and 1,3-di(N,N-dimethyldithiocarbamoyl)dithieno[3,4-b:3′,2′-d]-pyridines, respectively, were obtained in varying yields. 3-Monosubstituted derivatives were obtained in some cases. The formation of 3,7-disubstituted derivatives was sometimes also observed.     

On the grignard reaction of 2-bromo-3-iodo- and 3-bromo-2-chlorothiophene

2-Bromo-3-iodo- and 3-bromo-2-chlorothiophene react with magnesium in the presence of 1,2-dibrornoethane to give 2-halo-3-thiophene magnesium halide which opens a useful route to 2,3-disubstituted thiophenes having an electron-withdrawing group in the 3-position.