Acyclic analogs of nucleosides. Synthesis of hydroxyalkylbenzimidazoles and -benzotriazoles

Condensation of trimethylsilyl derivatives of benzimidazole and benzotriazole with alkylating agents in the presence of trimethylsilyl trifluoromethanesulfonate or SnCl₄, or direct alkylation of the sodium salts of benzimidazole and benzotriazole, gives 1-(2,3-dihydroxypropyl)-, 1-(3-hydroxy-2-oxabutyl)-, 1-(3-hydroxymethyl-4-hydroxy-2-oxabutyl)-, and 1-(1,5-dihydroxy-3-oxapent-2-yl)benzimidazole and -benzotriazole.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 198–202, February, 1988.     

Transformations of 2-(3-Hydroxy-3-methyl-1-butynyl)adamantan-2-ol >Catalyzed by Acids

Reaction of 2-(3-hydroxy-3-methyl-1-butynyl)adamantan-2-ol with acetonitrile under Ritter reaction conditions is accompanied by isomerization and partial hydration where the water addition to the triple bond occurs nonselectively. As a result of reaction carried out in the presence of 8 equiv of sulfuric acid a mixture was obtained of N ²-[4-(1-acetylamino-2-adamantyl)-2-methyl-3-butyn-2-yl]acetamide, N ³-[1-(1-acetylamino-2-adamantyl)-3-methyl-2-oxo-3-butyl]-acetamide, and N ³-[1-(1-acetylamino-2-adamantyl)-3-methyl-1-oxo-3-butyl]acetamide in ~10:3:2 ratio. In the presence of 2 equiv of the acid the mixture obtained consisted of N ²-[4-(1-acetylamino-2-adamantyl)-2-methyl-3-butyn-2-yl]acetamide, N ³-[1-(1-acetylamino-2-adamantyl)-3-methyl-2-oxo-3-butyl]acetamide, and 1-(1-acetylamino-2-adamantyl)-3-methyl-2-buten-1-one in the same ratio. In Rupe reaction conditions we obtained instead of the expected ,-unsaturated ketones a mixture of 1-(1-hydroxy-2-adamantyl)-3-hydroxy-3-methylbutan-1-one and 1-(1-hydroxy-2-adamantyl)-3-hydroxy-3-methylbutan-2-one in a 5:3 ratio.     

N-(2-tetrahydrofuranyl)azole nucleoside analogs by reactions of azoles with dihalomethanes in tetrahydrofuran

The reactions of the mono-N-substituted bispyrazolylpyridine 2-(1-methyl-4,5,6,7-tetxahydroindazol-3-yl)-6-(2H-4,5,6,7-tetrahydroindazol-3-yl)pyridine, 3,5-dimethylpyrazole and benzimidazole with sodium hydride and diiodomethane or dibromomethane in tetrahydrofuran produced the unexpected N-tetrahydrofuran-2-yl adducts as well as the expected diazolylmethanes. These side-reactions are thought to involve the 2-halo tetrahydrofuran derivative resulting from a free-radical halogenation by the dihalomethane.     

苯并咪唑衍生配体锌-铕(或铽)异金属双核配合物的合成、结构与光学性质

合成了四个锌-铕(或铽)异金属双核配合物[ZnLnL¹(NO₃)₃Py] (Ln=Eu (1), Tb (2); HL¹=1-H-2-(2-羟基-3-甲氧基苯基)苯并咪唑; Py=吡啶)和[ZnLnL²(NO₃)₃Py] (Ln=Eu (3), Tb (4); HL²=1-H-2-(2-羟基-3-甲氧基-5-溴苯基)苯并咪唑; Py=吡啶), 其中1、2、3是单晶态, 化合物4则为多晶样品; 通过单晶X射线衍射、元素分析、傅里叶变换红外光谱和电喷雾质谱对化合物进行了表征. 化合物的紫外-可见吸收光谱、荧光激发和发射光谱表明配体的激发态能量有效传递到配合物中的镧系金属离子中, 含有铽(III)离子的配合物发射出其特征发射光谱, 而含有铕(III)离子的配合物由于其它去活方式, 没有辐射出铕(III)离子的特征发射光谱.     

Condensed Pyridine Bases. Synthesis and Reactions of Benzofuro[2,3-c]indeno[2,1-e]-, Benzothieno[2,3-c]Indeno[2,1-e]-, Benzofuro-[3,2-c]Indeno[2,1-e]- and Thieno[2,3:4′,5′]-thieno[3,2-c]indeno[2,1-e]pyridines

Condensation of hetarene carboxaldehydes with phthalide gave 2-(3-hydroxy-1-oxoinden-2-yl)benzo[b]furan and 2-(3-hydroxy-1-oxoinden-2-yl)-5-ethylthieno[2,3-b]thiophene. Starting from hetaryl acetic acids gave 3-(3-hydroxy-1-oxoinden-2-yl)benzo[b]furan and 3-(3-hydroxy-1-oxoinden-2-yl)benzo[b]thiophene. Acylation of 3-hydroxy-1-oxoinden-2-yl-substituted heterocycles using acetic anhydride in the presence of 70% HClO₄ leads to the formation of pentacyclic pyrilium salts. Pentacyclic indenopyridines are prepared by treating the pyrilium salts with ammonia. The reaction of the carbonyl group in the indenopyridines with hydroxylamine, hydrazine hydrate, and in reduction using NaBH₄ has been studied.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 435–443, March, 2005.     

Zeolite-catalyzed synthesis of nicotinyl-fused indolo-pyrazoles and evaluation of their activities against Anopheles arabiensis and Lipoxygenase

A series of nicotyl-fused indolo-pyrazoles (NFIPs) were synthesized by a one-pot multicomponent reaction of aryl aldehydes, isoniazid, and indole in the presence of zeolite as a catalyst. Structures of all the synthesized compounds were established by IR, ¹H-NMR, ¹³C-NMR, 2D-NMR, TOF-MS, and elemental analysis. The products were obtained in excellent yields and high purity. All 10 compounds were screened for larvicidal and insecticidal properties against Anopheles arabiensis and tested for their lipoxygenase inhibitory activity. Compounds (3-(3-hydroxy-4-methoxyphenyl)-2,3-dihydropyrazolo[4,3-b]indol-1(4H)-yl)(pyridin-4-yl)methanone ( 4i ) and (3-(3-bromo-5-hydroxy-4-methoxyphenyl)-2,3-dihydropyrazolo[4,3-b]indol-1(4H)-yl)(pyridin-4-yl)methanone ( 4j) displayed highest larvae mortality at a 4 μg/ml dose in 24 h. Compounds (3-(4-methoxyphenyl)-2,3-dihydropyrazolo[4,3-b]indol-1(4H)-yl)(pyridin-4-yl)methanone ( 4h ) and (3-(3-hydroxy-4-methoxyphenyl)-2,3-dihydropyrazolo[4,3-b]indol-1(4H)-yl)(pyridin-4-yl)methanone ( 4i ) showed a significant knockdown activity after 24 h with 70% mortality. Furthermore, (3-(4-chlorophenyl)-2,3-dihydropyrazolo[4,3-b]indol-1(4H)-yl)(pyridin-4-yl)methanone ( 4c ) and (3-(3-bromo-5-hydroxy-4-methoxyphenyl)-2,3-dihydropyrazolo[4,3-b]indol-1(4H)-yl)(pyridin-4-yl)methanone ( 4j ) displayed promising lipoxygenase inhibitory activity with a mortality of 70% and 60%, respectively.     

An Insight into All Tested Small Molecules against Fusarium oxysporum f. sp. Albedinis: A Comparative Review

Bayoud disease affects date palms in North Africa and the Middle East, and many researchers have used various methods to fight it. One of those methods is the chemical use of synthetic compounds, which raises questions centred around the compounds and common features used to prepare targeted molecules. In this review, 100 compounds of tested small molecules, collected from 2002 to 2022 in Web of Sciences, were divided into ten different classes against the main cause of Bayoud disease pathogen Fusarium oxysporum f. sp. albedinis (F.o.a.) with structure–activity relationship (SAR) interpretations for pharmacophore site predictions as (δ⁻···δ⁻), where 12 compounds are the most efficient (one compound from each group). The compounds, i.e., (Z)-1-(1.5-Dimethyl-1H-pyrazole-3-yl)-3-hydroxy but-2-en-1-one 7, (Z)-3-(phenyl)-1-(1,5-dimethyl-1H-pyrazole-3-yl)-3-hydroxyprop-2-en-1-one 23, (Z)-1-(1,5-Dimethyl-1H-pyrazole-3-yl)-3-hydroxy-3-(pyridine-2-yl)prop-2-en-1-one 29, and 2,3-bis-[(2-hydroxy-2-phenyl)ethenyl]-6-nitro-quinoxaline 61, have antifungal pharmacophore sites (δ⁻···δ⁻) in common in N1---O4, whereas other compounds have only one δ⁻ pharmacophore site pushed by the donor effect of the substituents on the phenyl rings. This specificity interferes in the biological activity against F.o.a. Further understanding of mechanistic drug–target interactions on this subject is currently underway.     

Polarity and structure of 2-(1-methylbenzimidazol-2-yl)-1-phenyl- and -1,2-diphenyl-1-nitroethenes

Polarity of 2-(1-methylbenzimidazol-2-yl)-1-phenyl- and -1,2-diphenyl-1-nitroethenes was determined and their structure was studied using electronic and ¹H, ¹³C NMR spectroscopy, dipole moments measuring, XRD analysis, and quantum-chemical calculations. It was shown that the 2-(1-methylbenzimidazol-2-yl)-1-nitro-1-phenylethene has Z-configuration both in crystal and solution. The nitro group and benzimidazole substituent in its molecule are removed from the plane of the double bond. For 1,2-diphenyl-1-nitroethene E-structure is typical.     

Synthesis of 1,5-Disubstituted 3-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines

A series of 1,5-disubstituted 3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines were synthesized by the reaction of α,β-unsaturated ketones derived from dehydroacetic acid and hydrazine in hot acetic acid or propionic acid. The structures of all new compounds were elucidated by microanalyses, ¹H and ¹³C NMR, IR, and mass spectroscopic measurements.     

Synthesis of 1,5-Disubstituted 3-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines

Summary. A series of 1,5-disubstituted 3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-pyrazolines were synthesized by the reaction of α,β-unsaturated ketones derived from dehydroacetic acid and hydrazine in hot acetic acid or propionic acid. The structures of all new compounds were elucidated by microanalyses, ¹H and ¹³C NMR, IR, and mass spectroscopic measurements.     

Synthesis of some benzimidazole- and benzothiazole-derived ligand systems and their precursory diacids

Procedures are described for the preparation of various bidentate and linear tetradentate benzimidazoles and benzothiazoles incorporating units such as pyridyl and thioether, and for the preparation of certain thioether dicarboxylic acids precursory to them. Condensations of ortho-functinal anilines with carboxylic acids were carried out in polyphosphoric acid or refluxing HCl solution. Syntheses are reported for: [HO₂C(CH₂)2S(CH₂)₂]₂X (X = O, S), 1,9-bis(benzimidazol-2-yl)-2,5,8-trithianonane, 1,11-bis(N-methylbenzimidazol-2-yl)-3,6,9-trithiaundecane, 1,11-bis(2-benzimidazol-2-yl)-6-oxo-3,9-dithiaundecane, 2-(2-pyridyl)benzothiazole, 2,6-bis(benzothiazol-2-yl)pyridine, 2-(2-pyridyl)-N-methylbenzimidazole, 2-(2-pyridylmethyl)benzimidazole and 2-(N-methyl-2-piperidyl)benzimidazole. The compounds were characterized, where appropriate, by their mass, uv and ¹H-nmr spectra.     

Synthesis of Some 2-(3-Alkyl/aryl-5-trifluoromethylpyrazol-1-yl)-4-(coumarin-3-yl)thiazoles as Novel Antibacterial Agents

Abstract

Herein, we describe a one-pot synthesis of some novel 2-(3-alkyl/aryl-5-trifluoromethylpyrazol-1-yl)-4-(coumarin-3-yl)thiazoles (6) involving the reaction of 3-alkyl/aryl-5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazole-1-thiocarboxamides (3) with 3-bromoacetylcoumarins (5) in the presence of sodium carbonate in ethanol. Reaction of 3 with 5 in the absence of sodium carbonate, however, resulted in the formation of 2-(3-alkyl/aryl-5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-yl)-4-(coumarin-3-yl)thiazoles, which were subsequently dehydrated to 6 by refluxing in ethanol in the presence of sodium carbonate. The structure of the synthesized compounds (6) was confirmed by infrared (IR), mass, ¹H NMR, and ¹³C NMR spectra and elemental analysis data. Newly synthesized compounds (6) showed moderate to good activity against Gram-positive bacteria.     

A general synthesis of side chain derivatives of Δ9-thc

The synthesis of (6aR, 10aR)-trans-3-[1′,3′-dithian-2′-yl]-6a,7,8,10a-tetrahydro-6,6,9- trimethyl-6H-dibenzo[b,d]pyran-l-ol t-butyldimethylsilyl ether ($\text{4b}$) is reported. The use of this compound as a source of side chain derivatives of cannabinoids is illustrated by syntheses of 1′-,2′-,3′- and 4′-hydroxy-Δ⁹-THC, and 3-carboxy-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-1-o1 ($\text{6}$).     

Polyimides with low coefficient of thermal expansion derived from diamines containing benzimidazole and amide: Synthesis,properties, and the N-substitution effect

Three novel diamines, incorporating benzimidazole and amide moieties, namely 4-amino-N-(5-amino-benzimidazol-2-yl)-benzamide (6a), 4-amino-N-(5-amino-1- methyl-benzimidazol-2-yl)-benzamide (6b), and 4-amino-N-(5-amino-1-phenyl -benzimidazol-2-yl)-benzamide (6c), were designed and synthesized. A series of poly(benzimidazole-amide-imide) (PBIAI) films were prepared from the resulting diamines and 4,4-biphthalic dianhydride (BPDA). These flexible polyimides (PIs) showed high glass transition temperatures (T_g = 353–379°C), low coefficients of thermal expansion (CTE = 3.7–12.3 ppm K⁻¹) and good mechanical properties (σ = 152–207 MPa and E = 4.5–7.7 GPa), promising candidates for applications in flexible-display substrates. Furthermore, the data guided a feasible method to enhance T_g and reduce CTE by introducing benzimidazole and amide units into PI main chains, and the effect of different N-substituents on performance was revealed.     

Regioselective Synthesis of 5- and 3-Hydroxy-N-Aryl-1H-Pyrazole-4-Carboxylates and Their Evaluation as Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase

In silico evaluation of various regioisomeric 5- and 3-hydroxy-substituted alkyl 1-aryl-1H-pyrazole-4-carboxylates and their acyclic precursors yielded promising results with respect to their binding in the active site of dihydroorotate dehydrogenase of Plasmodium falciparum (PfDHODH). Consequently, four ethyl 1-aryl-5-hydroxy-1H-pyrazole-4-carboxylates and their 3-hydroxy regioisomers were prepared by two-step syntheses via enaminone-type reagents or key intermediates. The synthesis of 5-hydroxy-1H-pyrazoles was carried out using the literature protocol comprising acid-catalyzed transamination of diethyl [(dimethylamino)methylene]malonate with arylhydrazines followed by base-catalyzed cyclization of the intermediate hydrazones. For the synthesis of isomeric methyl 1-aryl-3-hydroxy-1H-pyrazole-4-carboxylates, a novel two-step synthesis was developed. It comprises acylation of hydrazines with methyl malonyl chloride followed by cyclization of the hydrazines with tert-butoxy-bis(dimethylamino)methane. Testing the pyrazole derivatives for the inhibition of PfDHODH showed that 1-(naphthalene-2-yl)-5-hydroxy-1H-pyrazole-4-carboxylate and 1-(naphthalene-2-yl)-, 1-(2,4,6-trichlorophenyl)-, and 1-[4-(trifluoromethyl)phenyl]-3-hydroxy-1H-pyrazole-4-carboxylates (~30% inhibition) were slightly more potent than a known inhibitor, diethyl α-{[(1H-indazol-5-yl)amino]methylidene}malonate (19% inhibition).     

Cyanoacetylene and Its Derivatives: XXVIII. Reactions of 2-Mercaptobenzothiazole with Nitriles of αα,ββ-Acetylene γγ-Hydroxyacids and with 3-Phenyl-2-propynonitrile

Nucleophilic addition of 2-mercaptobenzothiazole to 4-alkyl-4-hydroxy-2-alkynonitriles at 1:1 ratio in the presence of 4-6 wt% of Et₃N occurs regio- and stereospecifically to afford (Z)-4-alkyl-3-(benzothiazolyl-2-thio)-4-hydroxy-2-alkenonitriles (yield 40-51%). In the presence of 1.3 wt% of Dabco the thiazole and 4-hydroxy-4-methyl-2-pentynonitrile (1:1) give rise to a mixture of 2-alkenonitrile and 2-(3,3,6,6-tetramethyl-2-cyanomethyl-5-cyanomethylene-1,4-oxathian-2-yl)thiobenzothiazole. At the use of 4-6 wt% of LiOH arises an intractable mixture containing 1,4-oxathiane, benzothiazol-2-one, 2-[1-(5,5-dimethyl-2-cyanomethyl)-4-cyanomethylene-1,3-oxathiolan-2-yl)-1-methylethyl]thiobenzothiazole, bis(2,2,5,5-tetramethyl-6-cyanomethyl-3-cyanomethylene-1,4-oxathian-6-yl) disulfide, bis[1-(5,5-dimethyl-2-cyanomethyl-4-cyanomethylene-1,3-oxathiolan-2-yl)-1-methylethyl] disulfide, and 3-[1-(5,5-dimethyl-2-cyanomethyl-4-cyanomethylene-1,3-oxathiolan-2-yl)-1-methylethyl]benzothiazol-2-one (according to ¹H and ¹³C NMR data). 2-mercaptobenzothiazole adds to 3-phenyl-2-propynonitrile in the presence of 7 wt% of KOH with regio- and stereospecific formation of (Z)-3-(benzothiazolyl-2-thio)-3-phenyl-2-propenonitrile (88%).     

Chemistry of iminofurans: X. Synthesis and hydrolysis of 5-aryl(hetaryl)-2-[(4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]furan-3(2<Emphasis Type="Italic">H</Emphasis>)-ones

5-Aryl(hetaryl)furan-2,3-diones reacted with N-(triphenyl-λ⁵-phosphanylidene)-4,5,6,7-tetrahydro-1-benzothiophen-2-amines to give 5-aryl(hetaryl)-2-[(4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]furan-3(2H)-ones whose acid hydrolysis afforded 4-aryl(hetaryl)-2-hydroxy-4-oxo-N-(4,5,6,7-tetrahydro-1-benzothiophen- 2-yl)but-2-enamides.     

Synthesis and Analgesic Activities of Some 2-(Benzazolylacetyl)amino-3-ethoxycarbonylthiophene Derivatives

In this study, some 2-[2-(benzazole-2-thioxy)acetylamino]-3-ethoxycarbonylthiophene and 2-[2-(benzazole-1-yl)acetylamino]-3-ethoxycarbonylthiophene compounds were obtained by the reaction of 2-chloroacetylamino-3-ethoxycarbonylthiophene derivatives and a suitable benzazole-2-thione or benzimidazole derivatives. Analgesic activities of the compounds were tested by using tail-flick and tail-immersion methods. It is reported that some of the compounds showed remarkable analgesic activities.     

Synthesis of 3-(3-Methyl-1-aryl-1H-pyrazol-5-yl)-2H-2-chromen-2-one Derivatives via a One-Pot,Three-Component Reaction

An efficient synthesis of 3-(3-methyl-1-aryl-1H-pyrazol-5-yl)-2H-2-chromen-2-one derivatives by the reaction of salicylaldehydes, 4-hydroxy-6-methyl-2H-pyran-2-one, and arylhydrazine in acetonitrile under reflux condition and in the presence of piperidine is reported. This three-component reaction has some advantages such as ease of handling, good yields, and easy purification. All structures were confirmed by infrared, mass, ¹H NMR, and ¹³C NMR spectroscopy.     

Synthesis of elastomeric polypropylene in bulk using C 1-symmetric ansa-metallocenes. New aspects of the synthesis of 1-(fluoren-9-yl)-2-(2-methyl-5,6-dihydrocyclopenta [f]-1H-inden-1-yl)ethane and complexes of zirconium and hafnium with this ligand

Isomeric 1-(fluoren-9-yl)-2-(2-methyl-5, 6-dihydrocyclopenta [f]-1 H-indenyl) ethanes 1a,b and C ₁-symmetric metallocenes, viz., rac-1-(η⁵-fluoren-9-yl)-2-(2-methyl-5, 6-dihydrocyclopenta [f]-η⁵-inden-1-yl) ethanezirconium dichloride (9) and rac-1-(η⁵-fluoren-9-yl)- 2-(2-methyl-5, 6-dihydrocyclopenta [f]η⁵-inden-1-yl)ethanehafnium dichloride (10), with these ligands were synthesized by modified procedures. The structures of compounds 1b (two crystalline modifications) and 10 were established by X-ray diffraction analysis. The synthesis of polypropylene (PP) in bulk was studied in the presence of polymethylalumoxane-activated metallocenes 9 and 10 in the temperature range of 30–70°C. It was demonstrated that triisobutylaluminum can be used as a cocatalyst. In this case, the molecular weight of PP increases by a factor of ∼2. An increase in the reaction temperature leads to an increase in stereoregularity and crystallinity of PP. The polymer synthesized at high temperatures crystallizes in the γ form. The resulting PP is characterized by a wide range of properties from rigid crystalline thermoplastic to amorphous elastomeric. Samples, which have a high molecular weight and moderate isotacticity, exhibit high elastomeric and durability properties.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 400–413, February, 2005.