2-苄基-1,3-二氢-4-异喹啉酮及其衍生物的合成

本文合成了2-苄基-1,3-二氢-4-异喹啉酮的四种3-位亚甲基取代衍生物，四种氧酰基肟和两种6-苄基-5H-异喹啉并[4,3-b]喹啉衍生物。新化合物的结构经元素分析、红外光谱、核磁共振谱证实。     

通过Heck反应合成3-(2-羧基乙基)-1H-吡咯[2,3-b]吡啶-2-甲酸

以1H-吡咯[2,3-b]吡啶-2-甲酸乙酯为起始原料,经5步反应合成了新化合物3-(2-羧基乙基)-1H-吡咯[2,3-b]吡啶-2-甲酸,其结构经1H NMR和HR-MS表征。合成中间(E)-1-Ts-3-(3-乙氧基-3-氧代丙基-1-烯基)-1H-吡咯[2,3-b]吡啶-2-羧酸乙酯的最佳反应(Heck)条件为:无水DMF为溶剂,Pd(OAc)2为催化剂,dppf为配体,三乙胺为碱,收率88%。     

6-氯-2-氯甲基-3-喹啉甲酸乙酯与胺的反应研究

以6-氯-2-氯甲基-3-喹啉甲酸乙酯(1)为底物,在溶剂无水乙醇中与胺及胺的衍生物2a-p反应,以较好的收率(64.8-77.7%)得到7-氯-2,3-二氢-1H-吡咯并[3,4-b]喹啉-1-酮衍生物,其中与芳胺反应生成N-芳基取代的化合物3a-i,与氨水、甲胺、乙胺和苄胺反应生成N-烷基取代的化合物3j-m,与乙二胺、丙二胺及丁二胺反应生成具有对称结构的化合物3n-p.该反应具有操作简便、条件温和等特点.所有化合物均为新化合物,其结构经IR、1H NMR、13C NMR、MS和HRMS得以证实.     

3-苯氧甲基-6-(2,4-二氟苯基)-7H-1,2,4-三唑并[3,4-b][1,3,4]噻二嗪的合成与晶体结构研究

由苯氧乙酸出发，经多步反应，制得3-苯氧甲基－4－氨基－5－巯基－1，2， 4－三唑，它与2-氯－2'，4'－二氟苯乙酮进行环化反应，生成3-苯氧甲基－6－（ 2,4-二氟苯基）－7H-1,2,4-三唑并[3,4-b][1,3,4]噻二嗪，通过元素分析、红外 光谱、核磁共振氢谱与碳谱、质谱进行表征，并利用单晶X射线衍射法测定其结构 。晶体属单斜晶系、P2_(1/c)空间群，a = 1.339(3) nm, b = 1.4683(4) nm, c = 0.8606(2) nm, β = 108.49(2)°, Z = 4, F(000) = 736, R_1 = 0.0509。还 对均三唑并噻二唑两类稠杂环的晶体结构作了比较。     

3－苯氧甲基－6－（2，4－二氟苯基）－7H-1,2,4-三唑并[3,4-b][1,3,4]噻二嗪的合成与晶体结构研究

由苯氧乙酸出发，经多步反应，制得3-苯氧甲基－4－氨基－5－巯基－1，2， 4－三唑，它与2-氯－2'，4'－二氟苯乙酮进行环化反应，生成3-苯氧甲基－6－（ 2,4-二氟苯基）－7H-1,2,4-三唑并[3,4-b][1,3,4]噻二嗪，通过元素分析、红外 光谱、核磁共振氢谱与碳谱、质谱进行表征，并利用单晶X射线衍射法测定其结构 。晶体属单斜晶系、P2_(1/c)空间群，a = 1.339(3) nm, b = 1.4683(4) nm, c = 0.8606(2) nm, β = 108.49(2)°, Z = 4, F(000) = 736, R_1 = 0.0509。还 对均三唑并噻二唑两类稠杂环的晶体结构作了比较。     

微波辐射下2-氨基苯并[h]喹唑啉衍生物的合成

2-芳亚甲基-3，4-二氢-2H-1（2H）-萘酮和碳酸胍在以乙二醇为溶剂、微波辐 射下反应，生成一系列新的2-氨基-4-芳基-5，6-二氢化苯并[h]喹啉衍生物，产物 的结构通过单晶X射线衍射分析确证。     

硝基或氯代Blebbistatin化合物的合成

以2-氨基-5-硝基苯甲酸或4-氯苯甲酸、1-苯基-2-吡咯烷酮为原料,经过酯化、亚胺合成、关环、不对称合成四步反应合成了2种新的Blebbistatin化合物:3a-羟基-6-硝基-1-苯基-1,2,3,3a-四氢-吡咯并[2,3-b-喹啉-4-酮或3a-羟基-7-氯-1-苯基-1,2,3,3a-四氢-吡咯并[2,3-b]-喹啉-4-酮.通过IR,1H NMR,元素分析证实其结构,并测定了一些重要中间体的单晶结构.初步研究化合物的光学性质发现,所合成的新Blebbistatin化合物的紫外吸收与荧光发射强度均比前人合成的Blebbistatin化合物高.     

(E)-6-氯-2-(4-三氟甲基苯乙烯基)-3-喹啉甲酸的合成及其环化（英文）

设计了以6-氯-2-氯甲基-3-喹啉甲酸乙酯(1)为起始化合物与4-三氟甲基苯甲醛(2)通过"一锅法"反应合成(E)-6-氯-2-(4-三氟甲基苯乙烯基)-3-喹啉甲酸(3),化合物3在PPA的作用下发生傅瑞德尔-克拉夫茨酰基化反应得到2-氯-10-三氟甲基-12H-苯并[4,5]卓酮并[1,2-b]喹啉-12-酮(4)。所合成的化合物3,4未见文献报道,其结构经红外光谱、核磁共振氢谱、核磁共振碳谱和高分辨质谱得以证实。     

含吡唑1,2,4-三唑噻二嗪衍生物的合成及抑菌活性

1-苯基-3-甲基-5-氯-4-吡唑甲醛与4-氨基-5-取代苯基-1,2,4-三唑-3-硫酮缩合生成4-(1-苯基-3-甲基-5-氯吡唑次甲亚胺基)-5-(取代苯基)-2H-1,2,4-三唑-3(4H)-硫酮,再烷基加成化为新型含吡唑基5,6-2H-1,2,4-三唑[3,4-b][1,3,4]噻二嗪衍生物。 化合物结构经¹H NMR、IR以及元素分析确认。 初步生物活性测试结果表明,在100 mg/L浓度下,化合物8a(3-(2-甲基苯基)-6-(5-氯-2-甲基-4-苯基吡唑)-7-(4-硝基苯基)-5H-1,2,4-三唑[3,4-b][1,3,4]噻二嗪)对黄瓜炭疽病的抑制率达90%。     

萘并吖啶二酮衍生物的合成

6-氯/6-溴-2-氯甲基-3-喹啉甲酸乙酯(1a,b)分别与1-萘酚(2a)和2-萘酚(2b)反应,经"三步一锅法"合成取代的2-萘氧甲基-3-喹啉甲酸衍生物3a-d;在PPA作为闭环试剂、135℃的条件下,经Friedel-Crafts反应得到取代的氧杂卓并[3,4-b]喹啉酮衍生物4a-d;再在碱性条件下发生1,2-Wittig重排和空气氧化生成取代的萘并吖啶二酮衍生物5a-d。所合成的新化合物3a-d,4a-d,5a-d均通过红外光谱、核磁共振氢谱、核磁共振碳谱和高分辨质谱进行结构表征。     

New 7-substituted quinolone antibacterial agents. The synthesis of 1-ethyl-1,4-dihydro-4-oxo-7-(2-thiazolyl and 4-thiazolyl)-3-quinolinecarboxylic acids

A series of 1-ethyl-1,4-dihydro-4-oxo-7-(4-thiazolyl)-3-quinolinecarboxylic acids and 1-ethyl-1,4-dihydro-4-oxo-7-(2-thiazolyl)-3-quinolinecarboxylic acids were prepared. Also prepared was 10-[2-(aminomethyl)-4-thiazolyl]-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid. Analogs with basic amine substituents on the thiazole moiety were found to have antibacterial activity.     

Studies on quinoline derivatives and related compounds. VI. A novel displacement reaction of 1-ethylquinolinium iodides with nucleophiles

The reaction of 4-amino- ( 3a ) and 4-anilino-3-carbethoxy-1-ethyl-6,7-methylenedioxy-quinolinium iodide ( 3b ) with nucleophilic reagents produced 7-substituted 4-amino-3-carboxy-1-ethyl-6-hydroxyquinolinium betaines ( 5b-d ) and 7-substituted 1-ethyl-1,4-dihydro-6-hydroxy-4-phenylimino-3-quinolinecarboxylic acid ( 6b-d ), respectively, which led to 7-substituted 1-ethyl-1,4-dihydro-6-hydroxy-4-oxo-3-quinolinecarboxylic acids ( 1b-d ) by alkaline hydrolysis. With a variety of 1-ethyl-1,4-dihydroquinoline carboxylates ( 16a-e ) these novel displacement reactions were attempted.     

Synthesis and Crystal Structure of Ethyl 3-（4-Chlorophenyl）-3,4-dihydro-6-methyl-4-oxo-2- （pyrrolidin-1-yl）furo[2,3-d]pyrimidine-5-carboxylate

The crystal structure of the title compound ethyl 3-（4-chlorophenyl）-3,4-dihydro-6- methyl-4-oxo-2-（pyrrolidin-1-yl）furo[2,3-d]pyrimidine-5-carboxylate （C20H20ClN3O4, Mr= 401.84） has been prepared and determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group P21/n with a = 20.6215（9）, b = 8.5311（4）, c = 21.6886（9） A^°, β = 91.607（1）°, V = 3814.0（3）A^°^3, Z = 8, Dc = 1.400 g/cm^3, F（000） = 1680, μ = 0.233 mm^-1, R = 0.0718 and wR = 0.1545 for 6717 observed reflections with I 〉 2σ（I）. X-ray diffraction analysis reveals two crystallographically independent molecules in the asymmetric unit.     

Synthesis and isomeric conversions of several 2-substituted 1,4-dihydro-4-oxo-3-quinolinecarboxylic acid derivatives

Ethyl ester derivatives of 6- and 8-substituted 2-methyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids have been synthesized by treatment of the diethyl ester of acetylmalonic acid with 2- or 4-substituted anilines. Condensation of these newly synthesized quinolinecarboxylic acid derivatives with 4-nitrobenzaldehyde resulted in the formation of 6- and 8-substituted 2-[2-(4-nitrophenyl)-vinyl]-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acids and ethyl esters of 6- and 8-substituted 2-[2-(4-nitrophenyl)vinyl]-4-acetoxy-3-quinolinecarboxylic acids. The tautomeric and conformational transformations of these newly synthesized compounds have also been investigated, using IR, NMR, and UV spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 931–938, July, 1988.     

Condensation reactions of 3-oxo-2-arylhydrazonopropanals with active methylene reagents: formation of 2-hydroxy- and 2-amino-6-substituted-5-arylazonicotinates and pyrido[3,2-c]cinnolines via 6π-electrocyclization reactions

3-Oxo-3-phenyl-2-(p-tolylhydrazono)propanal (1a) undergoes condensation with ethyl cyanoacetate in acetic acid in the presence of ammonium acetate to yield either 2-hydroxy-6-phenyl-5-p-tolylazonicotinic acid ethyl ester (6a) or 2-amino-6-phenyl-5-ptolyl-azonicotinic acid ethyl ester (8), depending on the reaction conditions. Similarly, other 3-oxo-3-aryl-2-arylhydrazonopropanals 1a,b condense with active methylene nitriles 2c,d to yield arylazonicotinates 6b,c. In contrast, 2-[(4-nitrophenyl)-hydrazono]-3-oxo-3-phenyl-propanal (1c) reacts with ethyl cyanoacetate to yield ethyl 6-(4-nitrophenyl)-2-oxo-2,6-dihydropyrido[3,2–c]cinnoline-3-carboxylate (11), via a novel 6π-electrocyclization pathway. Finally, 3-oxo-2-(phenylhydrazono)-3-p-tolylpropanal (1d) condenses with 2a-c to yield pyridazinones 13a-c.     

Studies on quinoline derivatives and related compounds. II. Synthesis of 5-substituted 1-ethyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid

The cyclization of m-substituted anilinomethylenemalonates ( 1 ) in the presence of polyphosphate ester and some other cyclizing agents gave mixtures of the isomeric ethyl 5- ( 2 ) and 7-substituted 4-hydroxy-3-quinolinecarboxylates ( 3 ), which led to mixtures of the corresponding quinolinecarboxylic acids ( 4 and 5 ) by hydrolysis. The proportions of 4 and 5 in the mixtures were determined on the basis of their nmr spectra. Novel 5-chloro- ( 8a ), 5-methyl- ( 8b ) and 5-nitro-1-ethyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids were prepared and evaluated for antimicrobial activities. No significant activity, however, was noted.     

Synthesis of 5-[2-(Phenoxy)ethyl] Derivatives of 6-Methyluracil, 6-Methyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one,and 2-Imino-6-methyl-2,3-dihydro-1H-pyrimidin-4-one

A synthesis of novel derivatives of 6-methyluracil, 6-methyl-2-thioxo-, and 2-imino-6-methyl-2,3-dihydro-1H-pyrimidin-4-one containing a 2-(phenoxy)ethyl substituent at position 5 of the pyrimidine ring has been carried out. It was found that 5-[2-(phenoxy)ethyl] derivatives of 6-methyl-2-thioxo- and 2-imino-6-methyl-2,3-dihydro-1H-pyrimidin-4-one are obtained by the condensation of the corresponding ethyl 3-oxo-2-(2-phenoxyethyl)butanoates with thiourea or guanidine. 6-Methyl-5-[2-(phenoxy)ethyl]uracils can be prepared by treating 6-methyl-5-[2-(phenoxy)ethyl]-2-thioxo-2,3-dihydro-1H-pyrimidin-4-ones with an excess of aqueous monochloroacetic acid solution. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1213–1217, August, 2005.     

Synthesis of Some New Thiazoles and Pyrazolo[1,5-a]pyrimidines Containing an Antipyrine Moiety

Ethyl 2-{2-[4-(2,3-dimethyl-5-oxo-1-phenyl-3-(pyrazolin-4-yl)]-2-cyano-1-(phenylamino)vinylthio}-acetate, 2-[4-(2,3-dimethyl-5-oxo-1-phenyl-(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]2-(4-oxo-3-phenyl-(1,3-thiazoilidin-2-ylidene))ethanenitrile, 2-[4-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]-2-(4-methyl-3-phenyl(1,3-thiazolin-2-ylidene))ethanenitrile, 2-(5-acetyl-4-methyl-3-phenyl(1,3-thiazolin-2-ylidene))-2-[4-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]ethanenitrile, and ethyl 2-(cyano(4-(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)thiazol-2-yl)methylene)-2,3-dihydro-4-methyl-3-phenylthiazole-5-carboxylate were synthesized by treatment of 2-(4-(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)thiazol-2-yl)-3-mercapto-3-(phenylamino)-acrylonitrile with appropriate halo ketones or halo esters. Also, 4-{2-[5,7-dimethyl-2-(phenylamino)(7a-hydropyrazolo[1,5-a]pyrimidin-3-yl](1,-thiazol-4-yl)}-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one derivatives were synthesized via reaction of 4-{2-[5-amino-3-(phenylamino)pyrazolin-4-yl](1,3-thiazol-2-yl)}-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one with β-diketone or β-keto ester. All synthesized compound were established by elemental analysis, spectral data, and alternative synthesis whenever possible.     

Synthesis of azoles from 3-[(3-hydrazino-3-oxopropyl)anilino]-and 3-[(3-hydrazino-3-oxopropyl)-4-methylanilino]propane hydrazides

Condensation of 3-[(3-hydrazino-3-oxopropyl)anilino]-and 3-[(3-hydrazino-3-oxopropyl)-4-methylanilino]propane hydrazides with 2,4-pentanedione, phenyl isocyanate or phenyl isothiocyanate (with subsequent work up of the semicarbazides obtained by base), and carbon disulfide gave respectively: 1-(3,5-dimethyl-1H-1-pyrazolyl)-3-[3-(3,5-dimethyl-1H-1-pyrazolyl)-3-oxopropylanilino]-1-propanone, 3-(2-{[2-(5-oxo-4-phenyl-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]anilino}ethyl)-4-phenyl-4,5-dihydro-1H-1,2,4-triazol-5-one and its thio analog, and 5-(2-{[2-(2-thioxo-2,3-dihydro-1,3,4-oxadiazol-5-yl)ethyl]anilino}ethyl)-2,3-dihydro-1,3,4-oxadiazole-2(3H)-thione plus their methyl derivatives. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1353–1358, September, 2007.     

Synthesis of 5,8-dihydro-5-oxo-2-(3- or 4-pyridinyl)-pyrido[2,3-d]pyrimidine-6-carboxylic acids and the reinvestigation of the thermal cyclization of diethyl (2-hydroxy-4-pyrimidinyl)amino-methylenemalonate

Diethyl [2-(3- or 4-pyridinyl)-4-pyrimidinyl]aminomethylenemalonates 5 prepared by the reaction between 2-(3- or 4-pyridinyl)-4-pyrimidinamines 3 and diethyl ethoxymethylenemalonate ( 4 ) were thermally cyclized to afford ethyl 5,8-dihydro-5-oxo-2-(3- or 4-pyridinyl)pyrido[2,3-d]pyrimidine-6-carboxylates 6 . The later were alkylated with ethyl iodide and then saponified to give 5,8-dihydro-8-ethyl-5-oxo-2-(3- or 4-pyridinyl)pyrido-[2,3-d]pyrimidine-6-carboxylic acids 2 . Thermal cyclization of diethyl (2-hydroxy-4-pyrimidinyl)amino-methylenemalonate ( 8 ) gave ethyl 1,6-dihydro-4,6-dioxo-4H-pyrimido[1,6-a]pyrimidine-3-carboxylate ( 10 ) instead of ethyl 5,8-dihydro-2-hydroxy-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate ( 9 ) as previously claimed.