Synthesis and reactions of [1]benzofuro[3,2-c]pyridine

(E)-3-(1-Benzofuran-2-yl)propenoic acid (I) was prepared from 1-benzofuran-2-carbaldehyde under the Doebner’s conditions. The obtained acid was converted to the corresponding azide II, which was cyclized by heating in diphenyl ether to [1]benzofuro[3,2-c]pyridin-1(2H)-one (III). This compound was aromatized with phosphorus oxychloride to chloroderivative IV which was reduced with zinc and acetic acid to the title compound V. [1]Benzofuro[3,2-c]pyridin-2-oxide (VI) was synthesized by reaction of V with 3-chloroperoxybenzoic acid in dichloromethane. Treatment VI with benzoyl chloride and potassium cyanide (Reissert-Henze reaction) was shown to produce the corresponding [1]benzofuro[3,2-c]pyridin-1-carbonitrile (VII). The title compound was used for preparation of complex compounds VIII, IX

Synthesis and Anticonvulsant activity of new 5-((1-(2-(4-substituted phenacyl bromide)-2-oxoethyl)-2-phenyl-1H-indol-3yl) methylene) pyrimidine-2, 4, 6(1H, 3H, 5H)-trione Derivatives

In the current scenario we have plant to study to synthesize novel indole derivatives (4a-d) and (5a-b) which have the target activity like anti-convulsion and anti microbial etc. In the primary phase, we synthesized 2-phenyl-1H-indole reacted with Phosphorus oxychloride and N, N’-dimethylformamide by using vilsmeier reagent formylation of a new compound 2-phenylindole-3-carbaldehyde (2). The 2-phenylindole-3-carbaldehyde was reacted with substituted phenacyl bromide, K2CO3 and TBAB (Tetra butyl ammonium bromide) into the presence of N, N’-dimethylformamide to gives [1-(2-(4-substituted phenacyl bromide)-2-oxoethyl)-2-phenylindole-3-carbaldehyde (3a-d). The compound [1-(2-(4- substituted phenacyl bromide)-2-oxo-ethyl)-2-phenylindole-3-carbaldehyde was permitted to mixed with various substituted phenacyl bromide gives corresponding indole derivatives. The indole derivatives (3a-d) were reacted with barbituric acid and thiobarbituric acid dissolved into the methanol at reflux for 4h to gives afforded compounds (4a-d) and (5a-b). The final indole barbituric derivatives (4a-d) and (5a-b) were synthesized from substituted phenacyl bromide by the react with methanol and recrystalized from ethanol. The last compound has been completed on the basis of spectra FT-IR and 1H NMR. All the value of FT-IR, 1H NMR, Solubility and TLC were considered to be prominent. The pharmacological screening through ear electrode induced current 50mA for 0.2 seconds in electro-convulsiometer for anticonvulsant activity. The synthesize compounds were establish to be 4b, 4c, 4d, and 5a. The compound 4c and 5a were established to be the most potent compound through compare to standard drugs phenytoin sodium.

On Pyridopyrazinol Chemistry: Synthesis of Chemiluminescent Substances

Our work on new chemiluminescent substances related to the marine luciferin coelenterazine (λmax = 465 nm) led us to attempt the synthesis of four nitrogen-rich pyridopyrazine-bearing analogues. Accordingly, the preparation of the corresponding benzyl-bearing pyridopyrazinols is studied. By varying the conditions for the condensation of phenylpyruvic acid with 1,2-diaminopyridine or 3,4-diaminopyridine, all the possible pyridopyrazin-2-ol regioisomers are isolated and properly characterized, including by means of crystallographic studies. The ensuing syntheses of the halogenated pyridopyrazines are fraught with difficulties ranging from extensive decomposition to an unexpected ring contraction. In one instance, the inherently reductive mixture of phosphorus oxychloride and phosphorus trichloride provides 2-benzyl-3-chloropyrido[2,3-b]pyrazine. This precursor is then transformed into the target O-acetylated luciferin (6,8-dibenzylimidazo[1,2-a]pyrido[3,2-e]pyrazin-9-yl acetate). The ‘benzo’ derivative of this analogue (i.e., 2,12-dibenzylimidazo[1′,2′:1,6]pyrazino[2,3-c]isoquinolin-3-yl acetate) is also prepared and the chemiluminescence emission spectra of these compounds are determined in a phosphate buffer (λmax = 546 and 462 nm).

Influence of the synthesis method of tert-butylated triphenyl phosphates on the operational properties of fire-resistant fluids

Three substituted aryl esters of orthophosphoric acid are the base component of fire-resistant fluids used in the lubricating and electro-hydraulic control system at steam and gas turbines of power plants. In this paper, we studied the possibility of improving the physicochemical and performance properties of phosphates, which are made of the raw materials available in the Russian Federation: phenol and 4-tert-butylphenol by reducing the content of an undesirable component - unsubstituted triphenyl phosphate, which is particularly vulnerable towards water. According to the results of the work, the conclusions were made: - a decrease in the content of triphenyl phosphate to a level of 1% and below leads to some improvement (reduction) of the air release time and an increase in the hydrolytic stability (represented as reducing the change in acid number after prolonged contact with water) of the fire-resistant fluid based on mixed esters. The degree of change of these properties is quantified. - it is possible to achieve the minimum content of triphenyl phosphate by changing the phosphorylation technology. By carrying out the process stepwise, the possibility of the interaction of phosphorus oxychloride with unsubstituted phenol is substantially eliminated, that is why there is almost no probability of an undesirable component formation in the resulting mixture of esters.

Design, Synthesis and Evaluation of New Bioactive Oxadiazole Derivatives as Anticancer Agents Targeting Bcl-2

A series of 2-(1H-indol-3-yl)-5-substituted-1,3,4-oxadiazoles, 4a–m, were designed, synthesized and tested in vitro as potential pro-apoptotic Bcl-2 inhibitory anticancer agents based on our previously reported hit compounds. Synthesis of the target 1,3,4-oxadiazoles was readily accomplished through a cyclization reaction of indole carboxylic acid hydrazide 2 with substituted carboxylic acid derivatives 3a–m in the presence of phosphorus oxychloride. New compounds 4a–m showed a range of IC50 values concentrated in the low micromolar range selectively in Bcl-2 positive human cancer cell lines. The most potent candidate 4-trifluoromethyl substituted analogue 4j showed selective IC50 values of 0.52–0.88 μM against Bcl-2 expressing cell lines with no inhibitory effects in the Bcl-2 negative cell line. Moreover, 4j showed binding that was two-fold more potent than the positive control gossypol in the Bcl-2 ELISA binding affinity assay. Molecular modeling studies helped to further rationalize anti-apoptotic Bcl-2 binding and identified compound 4j as a candidate with drug-like properties for further investigation as a selective Bcl-2 inhibitory anticancer agent.

Synthesis of sulfonamide derivatives containing the structural fragment of pyrazol-1-yl-pyridazine

Sulfonamide derivatives of heterocyclic compounds are promising targets for the search for new substances with specific biological activity. They are widely used as inhibitors of human carbonic anhydrases involved in the implementation of various biochemical processes. The presence of several heterocyclic systems in the structure of sulfonamides significantly increases the ability to bind to active sites of carbonic anhydrases and inhibit their activity. Therefore, the development of approaches to the preparation of sulfonamides of polynuclear heterocyclic compounds is of great scientific interest. This article proposes a multistage scheme for the synthesis and characterization of new sulfonamide derivatives of 1-aryl-6-pyrazol-1-yl-pyridazines. The synthesis of substituted pyrazol-1-yl-pyridazines was carried out by sequential conversion of arylpyridazinones by refluxing in phosphorus oxychloride to 3-chloro-6-arylpyridazines, at the next stage as a result of the nucleophilic substitution of activated chlorine in the pyridazine ring with hydrazine, arylpyridazines were obtained with the reaction Refluxing in butanol, the target compounds with a 3,5-dimethylpyrazole structural fragment were synthesized. The study of the regularities of the course of sulfonylchlorination of 1-aryl-6-pyrazole-1yl-pyridazines made it possible to establish the effect of the substrate structure on the direction of the process and the selectivity of the reaction, as well as on the possibility of the formation of disubstitution products. The corresponding disulfonyl chloride was obtained only in the case of sulfonylchlorination of 1-(4-methoxyphenylpyridazin-3-yl)-3,5-dimethyl-1H-pyrazole at 100 °С for 10 h. In this case, the hydrogen atoms in position 3 of the benzene ring and position 4 of the pyrazole ring. In all other cases, monosubstitution products were obtained at the 4-position of the pyrazole ring. This is evidenced by the data of 1H NMR spectroscopy. On the basis of the obtained sulfonyl chlorides, the corresponding mono- and disulfonamides were synthesized. Convincing proof of the structure of all the obtained compounds has been carried out by a combination of mass spectrometry and NMR spectroscopy data.

A review on synthetic routes for obtaining of 2,5-disubstituted 1,3,4-oxadiazoles via cyclodehydration and oxidative cyclization reactions

1,3,4-Oxadiazole core is a known pharmacophore fragment, which possesses a wide opportunities for chemical modification and established versatile pharmacological potential. Moreover, oxadiazole plays a vital role in many drug structures and various biologically active compounds. For the construction of 1,3,4-oxadiazole cycle, different synthetic methods can be employed. In particular, the cyclization of N,N′-diacylhydrazines is a very common and convenient way for the synthesis of 2,5-disubstituted 1,3,4-охаdiazoles. This approach includes dehydration followed by simultaneous cyclization of diacylhydrazines under the action of various dehydrating reagents – thionyl chloride, polyphosphoric acid, phosphorus pentoxide, acetic anhydride, phosphorus oxychloride, sulfuric acid etc. Another direction for the synthesis of non-condensed heterocyclic systems based on 1,3,4-oxadiazole is the oxidative cyclization of hydrazide-hydrazones, which are obtained by condensation of carboxylic acids hydrazides with appropriate aldehydes. The oxidizing reagents that are most commonly used in this reaction are potassium permanganate in acetone medium, bromine in acetic acid, Pb3O4 , chloramine-T etc. In this review, we attempt to highlight the detailed approaches for obtaining 1,3,4-oxadiazole derivatives based on cyclodehydration and oxidative cyclization reactions as the most commonly used methods of synthesis for this class compounds.