水溶性稠杂环均三唑并噻二唑体系的合成及生物活性(I): 哌嗪取代衍生物

4-氨基-5-吡啶-4-基-均三唑硫醇(1)在复合催化剂DMAP和TBAB作用下与对卤代苯甲酸经环缩合反应以高收率得到中间体6-(5-氯-3-甲基-1-取代苯基-1H-吡唑-4-基)-3-吡啶-3-基-均三唑并[3,4-b][1,3,4]噻二唑(2a～2c), 接着苯环卤原子与取代哌嗪在聚乙二醇催化作用下发生亲核取代反应得到相应的哌嗪游离碱(3a～3c). 其中, 单取代哌嗪游离碱3a与含功能基的卤代物缩合得到功能基取代的哌嗪衍生物(4a～4g). 这些产生的游离碱与盐酸反应得到相应的水溶性盐酸盐. 所合成新化合物的结构经元素分析和光谱数据表征, 并评价了它们的体外抗菌活性及构效关系.     

New N,S-Derivatives of Nitrodienes from Thioallyl-and Thiodibromopropyl Nitrodienes

Compound 3 and 5a, b were obtained from the reaction of 1,3,4,4-tetrachloro-1-thioallyl-2-nitro-1,3-butadiene (1) with thiomorpholine (2) and piperazine derivatives 4a, b in dichloromethane. The reaction of compound 1 and bromine gave compound 6. Compounds 8 and 10 were obtained from the reaction of 6 with 1-(diphenylmethyl)piperazine (7) and piperidine (9) in dichloromethane. The derivative 13 was synthesized from the reaction of 4-bromo-1,1,3,4-tetrachloro-2-nitro-1,3-butadiene (11) and allylmercaptane (12). Compounds 15 and 16a, b were obtained from the reaction of 1-allyl-4-bromo-1,3,4-trichloro-2-nitro-1,3-butadiene (13) with morpholine (14) and the piperazine derivatives 16a, b, in dichloromethane, respectively.     

A study of the Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one derivatives

Summary The Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 a) gave 7-hydroxy-8-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (3 a) and 2,3-dihydro-2,6-diphenyl-3-methyl-(7H)furo[2,3-h]-1-benzopyran-7-one (7 a). 2-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 b) afforded4 b and7 b. 8-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (12) gave only the alkali soluble product 7-hydroxy-8-methyl-6-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (13).3 a,4 b, and13 were further cyclized in acidic medium to9 a,10 b, and14 followed by dehydrogenation.This paper is dedicated to Dr. F. M. Dean, Department of Organic Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool, U. K., on his retirement     

N-烷基/芳基-N'-(4-芳基噻唑-2-基)-N"-糖基胍的合成及生物活性研究

2,3,4,6-四-O-乙酰基-β-D-吡喃葡萄糖基异硫氰酸酯(1)与2-氨基-4-取代苯基噻唑(2a～2b)反应, 生成糖基硫脲衍生物3a～3b, 再在伯胺存在下经氯化汞脱硫, 得到一系列新的N-烷基/芳基-N'-(4-芳基噻唑-2-基)-N"-糖基胍类化合物(4a～4e, 5a～5e). 所有新化合物的结构均经IR, ¹H NMR, MS谱和元素分析证实, 所得产物均为β-构型. 生物活性测试结果表明, 化合物4b和5d对HIV-1 PR表现出了较高的抑制活性.     

Application of a Model Building Approach to Molecular Mechanics (MM3) for Calculating Low‐Energy Conformations of Tetra‐O‐Acyl‐N,N′‐Dialkyl‐D‐Glucaramides

A model building approach was used in conjunction with the MM3 molecular mechanics program to find the low‐energy conformations of three tetra‐O‐acyl‐N,N′‐dimethyl‐d‐glucaramide molecules: tetra‐O‐propanoyl‐(2), 2‐methylpropanoyl‐(3) and 2,2‐dimethylpropanoyl‐N,N′‐dimethyl‐d‐glucaramide (4), and tetra‐O‐acetyl‐N,N′‐dihexyl‐d‐glucaramide (5). A set of models was chosen for calculation of the low‐energy conformations of parent tetra‐O‐acetyl‐N,N′‐dimethyl‐d‐glucaramide (1), with additional models required to simulate conformationally more complex diamides 2–5. The dominant low‐energy conformations of 2 and 3 were very similar to that from 1, whereas very sterically constrained 4, with four bulky pendant O‐2,2‐dimethylpropanoyl groups, and 5, with terminal n‐hexyl groups, adopted different conformations. Stereoregular alternating head tail–tail head and repeating head tail–poly(hexamethylene 2,3,4,5‐tetra‐O‐acetyl‐D‐glucaramide) oligomers were graphically generated to provide some insight into the possible conformations of the actual acylated polyamides in nonpolar solution.     

Properties of composite solid polymer electrolyte using hyperbranched polymer with ether-linkage

The cross-linked composite solid polymer electrolytes composed of poly(ethylene oxide), lithium salt (LiN(SO₂CF₃)₂), and a hyperbranched polymer whose repeating units were connected by ether-linkage (hyperbranched polymer (HBP)-2) were prepared, and their ionic conductivity, thermal properties, electrochemical stability, mechanical property, and chemical stability were investigated in comparison with the non-cross-linked or cross-linked composite solid polymer electrolytes using hyperbranched polymers whose repeating units were connected by ester-linkage (HBP-1a, 1b). The cross-linked composite solid polymer electrolyte using HBP-2 exhibited higher ionic conductivity than the non-cross-linked and cross-linked composite solid polymer electrolytes using HBP-1a and HBP-1b, respectively. The structure of the hyperbranched polymer did not have a significant effect on the thermal properties and electrochemical stability of the composite solid polymer electrolytes. The tensile strength of the cross-linked composite solid polymer electrolyte using HBP-2 was lower than that of the cross-linked composite solid polymer electrolyte using HBP-1b, but higher than that of the non-cross-linked composite solid polymer electrolyte using HBP-1a. The HBP-2 with ether-linkage showed higher chemical stability against alkaline hydrolysis compared with HBP-1a with ester-linkage.     

Reaction of perfluoro-2-methyl-2-pentene with cycloalkanone oximes: new examples of the Beckmann—Chapman rearrangement

The base-catalyzed reaction of cycloalkanone oximes (la,b) with perfluoro-2-methyl-2-pentene (PFMP) initially affords the addition products,i.e., fluoroalkyl ethers (2a,b). In the presence of KOH, the latter undergoes dehydrofluorination to give perfluoroalkenyl ethers (3a,b). Thermolysis of ethers3a,b results in compounds of two types — pyrrolines (4a,b) andN-perfluoroalkenyl lactams (5a,b). The latter are also prepared from PFMP and the corresponding lactams. The structure ofN-[perfluoro-(2-methyl-2-penten-3-yl)]-2-pyrrolidone (5c) was established by X-ray diffraction study.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1073–1077, June, 1994.     

SYNTHESIS OF NEW ANTHRACYCLINE DERIVATIVES CONTAINING PYRUVIC,ASPARTIC, OR N-ACETYLASPARTIC ACID MOLECULE

ABSTRACT

The new anthracycline analogues (2–10) as potential anticancer agents were synthesized from daunomycin (1a) and doxorubicin (1b). Compounds 2, 6, and 7 were prepared by the nucleophilic displacement type esterification of a 14-bromodaunomycin (1c) with a sodium pyruvate, aspartate, and N-acetylaspartic acid, respectively. Whereas compounds (3, 8) and (4, 9) were prepared by the reaction of daunomycin (1a) or doxorubicin (1b) with one equivalent of the corresponding acids in the presence of EDCI/PP, compounds (5, 10) were obtained from 1b by reaction with two equivalents of the corresponding acids in the same manner.     

ORGANISCHE PHOSPHORVERBINDUNGEN 85.1 HERSTELLUNG,EIGENSCHAFTEN UND BIOLOGISCHE WIRKUNG VON N-AMINOGLYPHOSATE UND AZAGLYPHOSATE

Abstract

The synthesis and the chemical, physical and spectral properties of N-aminoglyphosate ethylester (hydrazino-N′-carbethoxymethyl-N′-methylphosphonic acid) 4a, H₂OPCH₂N(NH₂)CH₂CO₂C₂H₅, of hydrazino-N′-carbethoxymethyl-N′-methyl-P-methylphosphinic acid 4b, CH₃(HO₂)PCH₂N(NH₂)-CH₂CO₂C₂H₅, and of azaglyphosate ethylester (hydrazino-N-carbethoxymethyl-N-methyl-phosphonic acid 9, H₂O₃PCH₂NHNHCH₂CO₂C₂H₅, are described. 4a, 9 and 10 exhibit plant growth regulating properties.     

THE BEHAVIOR OF N-PHENYLIMINOPHOSPHORANE TOWARDS o- AND p-QUINONES. NEW SYNTHESIS OF DIOXAZOLE AND OXADIAZOLE DERIVATIVES

ABSTRACT

N-Phenyliminophosphorane (1) reacts with 9,10-phenanthrenequinone (2a) to give the new products 2-phenylphenanthro[9,10-d][1,3,2]dioxazole (4a) and (10Z)-10-(phenylimino)-9(10H) phenanthrenone (4b). The reaction of 1 with 1,2-naphthoquinone (2b) afforded both the dioxazole derivative 5a and the known 2-anilino-naphthoquinone-1,4-anil (5b). On the other hand, 2,6-di-tert-butyl-2,3-diphenyl-2,3-dihydro-1,2,3-benzoxadiazole (6) was obtained from the reaction of (2c) with phosphinimine (1). Application of reagent 1 on 2d and 2e renders (6E)-2,3,4,5-tetrahalogeno-6-(phenylimino)-2,4-cyclohexadien-1-one 7a and 7b, respectively. Moreover, p-quinones (3a–3c) react with phosphinimine (1) to yield products 8, 9 and 10, respectively. Mechanisms accounting for the formation of the new products are discussed and the probable structures of the products are presented based on analytical and spectroscopic data.     

Synthesis and Antimicrobial Activities of Some 6-Methyl-3-Thioxo-2,3-Dihydro-1,2,4-Triazine Derivatives

Abstract

4-Arylidene-imidazole derivatives (4a,b) were readily prepared by reacting 4-am- ino-6-methyl-3–thioxo-2,3–dihydro[1,2,4]triazin-5(4H)-one (1) with 4-arylidene-2-phenyl- 4H-oxazol-5-one (2). Reaction of 1 with some aromatic aldehydes in presence of triethylphosphite exclusively afforded the corresponding aminophosphonates 5a-c. Reaction of 1 with 3-phenyl-1H-quinazoline-2,4-dione (6a) and/or 3-phenyl-2-thioxo-2,3-dihydro- 1H-quinazolin-4-one (6b) gave 2-(6-methyl-5-oxo-3-thioxo-2,5-dihydro-3H-[1,2,4]triazin-4-ylimino)-3-phenyl-2,3-dihydro-1H-quinazolin-4-one (7). Moreover, on treating 1 with 2-phenylbenzo[d][1,3]thiazine-4-thione (8), 6-methyl-4-(2-phenyl-4-thioxo-4H-quinazolin-3-yl)-3-thioxo-3,4-dihydro-2H-[1,2,4]triazine-5-one (9) was obtained in 65% yield. Reaction of 1 with 4-sulfonylaminoacetic acid derivatives (10a,b) afforded the corresponding sulfonamides (11a,b), respectively. Acid hydrolysis of 11a afforded 7-aminomethyl-3-methyl[1,3,4]thiadiazole[2,3-c][1,2,4]triazin-4-one (12). 4-Amino-6-methyl-3-(morpholine-4-ylsulfanyl)-4H-[1,2,4]triazin-5-one (14) was prepared by reacting compound 1 with morpholine in presence of KI/I₂, while 3,3′-bis(4-amino-6-methyl-5-oxo-triazinyl)disulfide (16) was obtained by oxidation of 1 with lead tetraacetate. The antimicrobial activity of the products was evaluated against Gram-positive and Gram-negative bacteria as well as the fungus Candida albicans.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures, and tables.]     

Synthesis of 1,4‐Diaryl‐piperazine‐2,5‐diones: New Behavior of N,N‐Dimethylformamide Dimethyl Acetal (DMFDMA)

Reactions of chloroacetamides (5) with N,N‐dimethylformamide dimethyl acetal gave 1,4‐diaryl‐piperazine‐2,5‐diones 11a–e in good yield, rather than 1,5‐diaryl‐3,7‐dimethoxy‐1H,5H‐[1,5]diazocine‐2,6‐diones (9a–e).     

Synthesis of 2-(2-methoxyethyl)- and 2-(2-thiomethoxyethyl)-aniline and related compounds

Summary 2-(2-Nitrophenyl)-ethanol (2) was methylated with dimethyl sulfate to give 2-(2-methoxyethyl)-1-nitrobenzene (3a) which then was reduced with hydrazine hydrate in the presence ofRaney nickel to 2-(2-methoxyethyl)-aniline (1a). Compound1a can be transformed into the N-monosilylated derivative4 by lithiation withn-butyllithium and subsequent reaction with chlorotrimethylsilane. Reaction of2 withp-toluenesulfonyl chloride yields 2-(2-nitrophenyl)-ethylp-toluenesulfonate (5), which reacts with sodium thiomethoxide to give 2-(2-nitrophenyl)-ethylp-toluenesulfonate (5), which reacts with sodium thiomethoxide to give 2-(2-thiomethoxyethyl)-1-nitrobenzene (3b).3b was reduced with hydrazine hydrate in the presence ofRaney nickel to yield 2-(2-thiomethoxyethyl)-aniline (1b). Ethyl (2-nitrophenyl)-acetate (6) could be dimethylated with methyl iodide in the presence of potassiumtert-butoxide and 18-crown-6 to give ethyl 2-methyl-2-(2-nitrophenyl)-propionate (7). Reduction of7 with lithium borohydride yields 2,3-dihydro-3,3-dimethyl-1H-indole (9) and 2-[(1-hydroxy-2-methyl)-2-propyl]-aniline (10).

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Synthese von 2-(2-Methoxyethyl)- und 2-(2-Thiomethoxyethyl)-anilin und verwandten Verbindungen

Zusammenfassung 2-(2-Nitrophenyl)-ethanol (2) wurde mit Dimethylsulfat zu 2-(2-Methoxyethyl)-1-nitrobenzol (3a) methyliert, das sich mit Hydrazinhydrat in Gegenwart vonRaney-Nickel zu 2-(2-Methoxyethyl)-anilin (1a) reduzieren läßt. Verbindung1a kann durch Metallierung mitn-Butyllithium und anschließende Reaktion mit Chlortrimethylsilan in dasN-monosilylierte Derivat4 umgewandelt werden. Reaktion von2 mitp-Toluolsulfonylchlorid ergab 2-(2-Nitrophenyl)-ethyl-p-Toluolsulfonat (5), das mit Natriumthiomethanolat zu 1-Nitro-2-(2-thiomethoxyethyl)-benzol (3b) reagiert.3b wurde mit Hydrazinhydrat in Gegenwart vonRaney-Nickel zu 2-(2-Thiomethoxyethyl)-anilin (1b) reduziert. Ethyl-2-(nitrophenyl)-acetat (6) kann mit Methyliodid in Gegenwart von Kalium-tert-butoxid und 18-Krone-6 zu Ethyl-2-methyl-2-(2-nitrophenyl)-propionat (7) dimethyliert werden. Reduktion von7 mit Lithiumborhydrid lieferte 2,3-Dihydro-3,3-dimethyl-1H-indol (9) und 2-[(1-Hydroxy-2-methyl)-2-propyl]-anilin (10).

     

Utility of 1‐Chloro‐3,4‐dihydronaphthalene‐2‐carboxaldehyde in the Synthesis of Novel Heterocycles with Pharmaceutical Interest

Ethyl α‐cyano‐β‐(1‐chloro‐3,4‐dihydronaphthalene‐2‐yl) acrylate (2) was prepared by the Knoevenagel condensation of 1 with ethyl cyanoacetate. Compound 2 was used as the key intermediate to prepare Schiff bases (3a, b), benzo[c]acridine (4), naphthyl thiopyrimidine (5), and pyrazolo[2,3‐a]‐benzo[h]quinazoline (6) derivatives through its reaction with hydrazines, p‐ansidine, thiourea, and 3,5‐diamino‐4‐phenylazopyrazole, respectively. Base‐catalyzed cyclocondensation of 1 with hippuric acid gives oxazolone derivative (7). Reaction of compound 7 with aniline gave imidazolone derivative (9). Treatment of compound 1 with different types of diaminopyrazoles gave 6,7‐dihydro‐pyrazolo[2,3‐a]‐benzo[h]quinazoline (10–13) derivatives. The multicomponent reaction of compound 1 with pyrazolone and malononitrile in the presence of ammonium acetate furnished pyrazolo[3,4‐b]‐benzo[h]quinoline (14) while in the presence of piperidine afforded benzo[h]chromeno[2,3‐c]pyrazole derivative 15.     

Synthesis of Fragments of the Capsular Polysaccharide of Haemophilus Influnzae Type B Part II. Preparation and Structural Analysis of Fragments Comprising two and Three Repeating Units

Abstract

The synthesis of spacer-containing fragments of the capsular poly-saccharide of H. influenzas, comprising two and three repeating units (9a and 9b, respectively), is presented. Ribosylribitol building blocks 1 and 2 were coupled with bis [1-benzotriazolyl]-2-chlorophenyl phosphate (3) to give the phosphotriester derivative 5a (72%), which was selectively deprotected at O-5 of the terminal ribitol residue (cleavage of the trans-1-propenyl ether) to afford compound 6a (82%). Repeated coupling of building block 2 with 6a (chain elongation), followed by propenyl- cleavage, gave analogue 6b. Both derivatives 6a and 6b were coupled with spacer 7 (chain termination). The fully protected fragments 8a (84%) and 8b (49%, starting from 6a) were thus obtained. Complete deprotection of 8a and 8b was achieved in three steps. After purification and cation-exchange, 9a and 9b were obtained in 41 and 68% yields, respectively. The structural integrity of the largest fragment (9b) was confirmed by FAB MS and various NMR spectroscopic techniques.     

SYNTHESIS OF (2,3,4,6-TETRA-O-ACETYL-α-D-GLYCOPYRANOSYL) THIOPHENE DERIVATIVES AS NEW C-NUCLEOSIDE ANALOGUES[1]

Treatment of 2-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)ethanal (1a) and 2-(2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl)ethanal (1b) respectively with malononitrile in the presence of silica gel provided the corresponding 4-[2,3,4,6-tetra-O-acetyl-α-D-glycopyranosyl]-2-cyanocrotononitriles (2a) and (2b). Starting from 2a and 2b, respectively, cyclizations with sulfur and triethylamine yielded 5-[2,3,4,6-tetra-O-acetyl-α-D-glycopyranosyl]-2-aminothiophene-3-carbonitriles (3a) and (3b). Further cyclizations could be achieved by utilizing of triethyl orthoformate/ammonia to furnish the 6-(α-D-glycopyranosyl)thieno[2,3-d]pyrimidine-4-amines 4a and 4b.     

DIBUTADIENYL PIPERAZINE,DIBUTADIENYL HOMOPIPERAZINES AND BUTADIENYL-SUBSTITUTED PIPERIDINES FROM MONOSUBSTITUTED HALODIENES

Compounds 3a–k were obtained from the reactions of compounds 1a–k with homopiperazine (2) in CH ₂ Cl ₂ . Compounds 1a–b, 1d–f, and 1h–l gave compounds 5a–b, 5d–f, and 5h–l with 2-methylpiperazine (4) in dichloromethane. Compounds 7c and 9c were obtained from the reactions of compound 1c with 4-ethoxycarbonyl piperazine (6) and 4-piperidinol (8) in CH ₂ Cl ₂ . Compounds 1a and 1f gave compounds 11a and 11f with 4-methylpiperazine (10), and compound 13f was obtained from the reactions of compound 1f with 4-methylpiperidine (12) in CH ₂ Cl ₂ .     

The reaction of 4-methoxycoumarins with prenyl bromide: Synthesis of 4′,4′,5′-trimethyl-dihydrofurano-coumarins and 2,2-dimethyl-chromenopyrans

The reaction of 7-hydroxy-4-methoxy- (1a), 7-hydroxy-4,5-dimethoxy-(1b) and 5-hydroxy-4,7-dimethoxy (1c) -2H-1-benzopyran-2-ones with prenyl bromide in acetone in the presence of anhydrous potassium carbonate gave the corresponding prenyloxycoumarins1d,1e, and1f. The prenyloxy coumarins1d,1e,1f onClaisen migration by refluxing inN,N-dimethyl aniline gave the corresponding 4,4,5-trimethyl-dihydrofuranocoumarins2a,2b, and3. However, the reaction of1a,1b, and1c with 3-chloro-3-methyl-but-1-yne in acetone in presence of potassium carbonate and potassium iodide gave the corresponding propargyl ethers1g,1h,1i, which on refluxing inN,N-dimethyl aniline gave the corresponding 2,2-dimethylchromenopyrans4a,4b, and5. These can also be obtained directly if the reaction is carried out in the presence of dioxan.

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Die Reaktion von 4-Methoxycumarinen mit Prenylbromid: Synthese von 4,4,5-Trimethyl-dihydro-furanocumarinen und 2,2-Dimethylchromenopyranen

Zusammenfassung Die Reaktion von 7-Hydroxy-4-methoxy-(1a), 7-Hydroxy-4,5-dimethoxy-(1b) und 5-Hydroxy-4,7-dimethoxy-2H-1-benzopyran-2-onen (1c) mit Prenylbromid in Aceton in der Gegenwart von wasserfreiem Kaliumcarbonat ergab die entsprechenden Prenylcumarine1d,1e und1f. Diese ergaben durchClaisen-Wanderung bei Rückfluß inN,N-Dimethylanilin die entsprechenden 4,4,5-Trimethyldihydrofuranocumarine2a,2b und3. Die Reaktion von1a,1b und1c mit 3-Chlor-3-methyl-1-butin in Aceton in Gegenwart von wasserfreiem Kaliumcarbonat und Kaliumjodid ergab die entsprechenden Propargylether1g,1h und1i, die ihrerseits bei Rückfluß inN,N-Dimethylanilin die jeweiligen 2,2-Dimethylchromenopyrane4a,4b und5 ergaben. Letztere können auch direkt erhalten werden, wenn die Reaktion in Gegenwart von Dioxan durchgeführt wird.

     

Synthesis and characterization of water-soluble arene-ruthenium complexes and their application in biphasic olefin oxidation

New water-soluble complexes [(η⁶-C₆H₆)RuCl(C₅H₄N-2-CH?=?N-R)]Cl (1) (with R?=?4-hydroxymethylphenyl (a), 2,4-dichlorophenyl (b), 2-fluorophenyl (c), 3-carboxyphenyl (d)) have been synthesized by reacting [(η⁶-C₆H₆)Ru(μ-Cl)Cl]₂ with the N,N′-bidentate ligands in a 1:2 ratio. Full characterization of all complexes was accomplished using ¹H and ¹³C NMR, elemental analyses, UV-Vis spectroscopy, IR spectroscopy and single crystal X-ray crystallography for determination of the structure of 1d, as 1d·4H₂O. The single crystal structure confirmed coordination of the ligand to the ruthenium(II) center leading to a structure commonly described as a pseudo-octahedral, three-legged piano stool. The geometry around the Ru(II) center is such that the arene ring occupies the apex of the stool while the N,N′-bidentate ligand and a chloride occupy the base of the stool. The synthesized Ru(II) complexes were tested as catalysts for oxidation of styrene using NaIO₄ as a co-oxidant in a biphasic system. All complexes were active, giving good yields of benzaldehyde. Catalyst 1c was later investigated for olefin oxidation and gave high yields of the corresponding aldehydes as the major products in all cases.     

Studies on Pyrazine Derivatives,XLIV: Synthesis and Tuberculostatic Activity of 4-Substituted 3,4,5,6-Tetrahydro-2H-[1,2′]-Bis-Pyrazine Derivatives

2-chloro-3-cyanopyrazine was a substrate in the syntheses of some potentially tuberculostatic pyrazine derivatives. This compound, upon action of secondary amines, pyrazine derivatives 1-phenyl-, 1-piperonyl-, 1-(4-fluorophenyl)-, 1-(2-pyridil)-, and 1-benzylpiperazine, gave the corresponding nitriles ( 1a–e ). Compounds 1c , d , e were changed into the amidoximes ( 2c , d , e ) by hydroxylamine action. Derivatives 1a–e were transformed into the corresponding thioamides ( 3a–e ) when treated with ammonium polysulphide. Two of these, thioamides, 3a and 3b , in the cyclization reactions with ethylenediamine gave the imidazolines ( 4a , b ) with phenacyl bromide—the thiazole derivatives ( 5a , b ). The compounds obtained were tested in vitro for their tuberculostatic activity. The tuberculostatic activity of compound 5b was the highest: MIC 3.1–7.8 μ g/mL.