借Wohl-Ziegler反应合成1-苯基-1,3-丙二醇及其他1-取代苯基-1,3-丙二醇的衍生物

1,本文叙述从3-苯基丙醇的3′,5′-二硝基苯甲酸酯借 Wohl-Ziegler 溴化反应合成 1-苯基-1,3-丙二醇。2.用相同方法从3-(邻取代基-对硝基苯基)-丙醇酯合成1-(邻取代基-对硝基苯基)-1,3-丙二醇的相应的衍生物。此方法各步产量较高,可以用作在连于苯环的碳原子上引入一个羟基的制备方法。3.含氨基的化合物进行 Wohl-Ziegler 溴化反应时,最好用邻苯二甲酰基,保护氨基。4.3-溴代-3-(邻苯二甲酰亚氨-对硝基苯基)-丙醇乙酸酯在乙酸氢溴酸混合液中水解,获得7-硝基喹啉。     

N-[5-(1-邻氯苯氧乙基)-1,3,4-噻二唑-2-基]N'-芳酰基脲的合成及其生物活性

N-[5-(1-邻氯苯氧乙基)-1;3;4-噻二唑-2-基]N'-芳酰基脲的合成及其生物活性;噻二唑;芳酰基脲;生物活性;生长素;细胞分裂素     

4-(硝基苯基)-3-硫代脲酸烷基酯类的合成及其生物活性研究

通过硝基苯胺同烷氧酰基异硫氰酸酯的化合反应以及钛酸丁酯的酯交换反应共合成了9个4-(硝基苯基)-3-硫代脲酸烷基酯类化合物(1-9)。通过各种波谱分析确定了它们的化学结构, 并研究了这类物质对农杆菌的抑制作用。     

2-氰基-3-取代丙烯酸(2-乙氧基乙基)酯的合成及除草活性

设计并合成了11个2-氰基-3-取代苯胺基-3-甲硫基丙烯酸(2-乙氧基乙基)酯(2)和11个2-氰基-3-取代苯基脲基丙烯酸(2-乙氧基乙基)酯(5)两类光合作用光系统Ⅱ(PSⅡ)电子传递抑制剂,目标化合物的结构均经1H NMR,13C NMR和质谱分析确证,生物活性测试结果表明:部分化合物2对双子叶杂草表现出良好的选择性和除草活性,化合物5苯环上间位有取代基时有一定的除草活性.     

1-芳基-4-吡唑-5-酰基氨基脲类化合物的合成及杀菌活性

为了寻求新的吡唑先导化合物, 用4-氯-1-甲基-3-乙基-5-吡唑甲酰肼与取代苯基异氰酸酯反应得到了14个新的1-吡唑酰基-4-芳基氨基脲类化合物. 经IR, 1H NMR, MS和元素分析对化合物的结构进行了表征. 初步生物活性实验结果表明, 在500 mg/mL浓度下, 化合物1-(4-氯-3-乙基-1-甲基-1H-吡唑-5-甲酰基)-4-(2-甲基苯基)氨基脲(4g), 1-(4-氯-3-乙基-1-甲基-1H-吡唑-5-甲酰基)-4-(2,4-二甲基苯基)氨基脲(4k)对小麦白粉病菌(Blumeria graminis)的抑制率分别达到90%和80%; 在25 mg/mL浓度下, 化合物1-(4-氯-3-乙基-1-甲基-1H-吡唑-5-甲酰基)-4-苯基氨基脲(4c)对黄瓜灰霉病菌(Botrytis cinerea)的抑制率达到70.1%; 化合物1-(4-氯-3-乙基-1-甲基-1H-吡唑-5-甲酰基)-4-苯基氨基脲(4c)和1-(4-氯-3-乙基-1-甲基-1H-吡唑-5-甲酰基)-4-(2-硝基苯基)氨基脲(4d)对稻瘟病菌(Pyricularia oryzae)的抑制率均达到51.3%.     

几个烯胺的邻硝基苯甲酰化和在酸水解中发生的重排

为了了解芳酰基化的效率和双酰基衍生物的形成, 对几个典型醛和酮的吗啉烯胺进行了邻硝基苯甲酰化的探索。丁醛和异丁醛吗啉烯胺的酰化正常, 水解分别生成55%的2-(邻硝基苯甲酰基)丁醛(2)和40%的2-(邻硝基苯甲酰基)异丁醛(3)。3-戊酮和1, 3-二甲氧基丙酮的吗啉烯胺在酰化和水解时分别生成37%和14.8%相应的β-二酮的烯醇邻硝基苯甲酸酯(4)和(5)。4和5的酸水解发生意外的1, 5-和1,3-酰基转位, 分别生成3, 5-二甲基-2, 6-双(邻硝基苯基)吡喃-4-酮(6)和2-甲氧基-2-甲氧乙酰基-1, 3-双(邻硝基苯基)-1, 3-丙二酮(7)。环戊酮和环已酮吗啉烯胺的酰化分别产生9%和34%的双酰基烯胺(9a)和(9b),逐次酸水解得到2-(邻硝基苯甲酰基)环戊酮(11a)和-环已酮(11b)。在总酰化产物的直接水解中, 11a的产率可以达到81%, 而11b只有35%。对双酰化进行了一些讨论。     

苯基及邻位取代苯基膦酸单烷基酯的合成及其萃取稀土的性能

提出了制备具长碳链酯烷基的烃基膦酸单烷基酯的合成方法。按此法合成了高纯度的苯基膦酸单(2-丁基辛基)酯、苯基膦酸单(1-甲基月桂基)酯、邻甲苯基膦酸单(2-丁基辛基)酯及邻甲苯基膦酸单(1-甲基月桂基)酯,考察了它们对以镧、镨、钕及镥为代表的轻、重稀土的萃取性能,并研究了萃取配合物的组成、结构和萃取分离稀土的机理。     

盐酸尼非卡兰的合成

以N，N′-二甲基脲为原料，经氰乙酸环合、乙醇胺脱氨、二氯亚砜氯化3步反应合成了关键中间体6-(2-氯乙基)胺基-1，3-二甲基-嘧啶二酮(7)。7再与：N-(2-羟乙基)-3-(4-硝基苯基)丙胺反应得抗心律失常药盐酸尼非卡兰，总收率为48．0％(以N，N′-二甲基脲计)，其结构经NMR和MS确认。     

4-[4’-(二乙基氨基)苯乙烯基]-N-(4″-乙氧基苯基)-N-(4-氨基苯基)苯胺的合成

对硝基苯胺和对碘苯乙醚经取代反应制得4’-硝基-(4-乙氧基苯)苯胺(3);3与对氟苯甲醛经取代反应制得含乙氧基的脂溶性中间体4-[(4’-乙氧基苯基)(4″-硝基苯基)氨基]苯甲醛(5);5与4-N,N-二乙基胺基苄基三苯基鏻盐经Witting成烯反应后经Pd/C催化、水合肼还原合成了新化合物4-[4’-(二乙基氨基)苯乙烯基]-N-(4″-乙氧基苯基)-N-(4-氨基苯基)苯胺,其结构经1H NMR,IR,MS和元素分析表征。     

芳基噻唑联哌啶酰胺类化合物的合成及生物活性

为了寻找具有生物活性的新型芳香基噻唑联哌啶酰胺类先导化合物,设计并合成了15个未见文献报道的芳基噻唑联哌啶酰胺类化合物,其结构经1HNMR、13CNMR和HRMS确证,生物活性测定结果显示,部分目标化合物表现出高效的抑菌和杀虫活性,如在200μg/mL浓度下,5-(3-溴苯基)-4-甲基-2-(1-((4-硝基苯基)磺酰基)哌啶-4-基)噻唑(6b)对黄瓜霜霉病的抑菌活性为100%,优于嘧菌酯,5-(4-溴苯基)-2-(1-((4-氯苯基)磺酰基)哌啶-4-基)-4-甲基噻唑(6c)对水稻纹枯病的抑菌活性为58.86%,与嘧菌酯相当;在500μg/m L浓度下,(4-(5-(3-溴苯基)-4-甲基噻唑-2-基)哌啶-1-基)(间甲基苯基)酮(6h)对粘虫的杀虫活性为100%.     

Indoprofen类似物的合成和表征

以邻硝基苯甲醛为超始原料，合成2-溴甲基-3-喹啉酸乙酯中间体，其分别与 苯胺、2-氯代苯胺、3-氯代苯胺、2-甲基苯胺和3-甲基苯胺发生Williamson反应， Williamson反应产物经闭环反应，得到新化合物2，3-二氢-1-氧代-2-苯基-1H-吡 咯并[3，4-b]喹啉（4a），2，3-二氢-1-氧代-2-（2-氯代苯基）-1H-吡咯并[3， 4-b]喹啉（4b），2，3-二氢-1-氧代-2-（3-氯代苯基）-1H-吡咯并[3,4-b]喹啉（ 4c），2，3-二氢-1-氧代-2-（2-甲基苯基）-1H-吡咯并[3，4-b]喹啉（4d）和2， 3-二氢-1-氧代-2-（3-甲基苯基）-1H-吡咯并[3，4-b]喹啉（4e）。12个新化合物 由元素分析、红外光谱、核磁共振氢谱、质谱予以证实。     

Synthesis and antibacterial activity of 1-(substituted-benzyl)-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acids and their 6,8-difluoro analogs

Alkylation of 6,7-difluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester with substituted-benzyl chlorides gave 1-(substituted-benzyl)-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid ethyl esters. Their treatment with piperazine or N-methylpiperazine in pyridine yielded 1-(substituted-benzyl)-6-fluoro-1,4-dihydro-4-oxo-7-(l-piperazinyl)quinoline-3-carboxylic acid ethyl esters which were hydrolyzed with aqueous sodium hydroxide and then acidified with hydrochloric acid afforded the desired 1-(substituted-benzyl)-6-fluoro-1,4-dihydro-4-oxo-7-(1-iperazinyl)quinoline-3-carboxylic acids. The 6,8-difluoro analogs were prepared similarly using 6,7,8-trifluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester as a starting material. Some of these quinolones demonstrated fairly good antibacterial activities. Among them, 6-fluoro-1-(4-fluorophenylmethyl)-1,4-dihydro-7-(1-iperazinyl)-4-oxoquinoline-3-carboxylic acid ( 7d ) and 6,8-difluoro-1-(3-fluorophenylmethyl)-1,4-dihydro-7-(1-piperazinyl)-4-oxoquinoline-3-carboxylic acid ( 8c ) are two of the best.     

利用Reformatsky反应合成1-β-碳氢霉烯类抗生素中间体

以(2R)-3-[(3S,4R)-1-(叔丁基二甲基硅氧基)乙基]-4-乙酰氧基氮杂环丁-2-酮为母体,2-溴乙(丙)酸酯或2-溴丙酰胺为亲核试剂,通过Reformatsky反应合成了一系列新型的1-β-碳氢霉烯类抗生素中间体——3-{(2R)-2-[(3S,4R)-1-(叔丁基二甲基硅氧基)乙基]氮杂环丁-2-酮-4-基}乙(丙)酸酯(3a～3d)和3-{(2R)-2-[(3S,4R)-1-(叔丁基二甲基硅氧基)乙基]氮杂环丁-2-酮-4-基}-N,N-二取代丙酰胺(3e,3i和3k),其结构经1H NMR和13C NMR表征,其中3a～3e和3i未见文献报道。     

Fluorine-containing 3-arylhydrazono-2,4-dioxobutanoates in reactions with difunctional nucleophiles

3-Arylhydrazono-4-polyfluoroalkyl-2,4-dioxobutanoates reacted with hydrazines to give ethyl 4-aryldiazeno-3-polyfluoroalkyl-1H-pyrazole-5-carboxylates, while analogous reactions of ethyl 3-arylhydrazono-4-pentafluorophenyl-2,4-dioxobutanoates resulted in the formation of 4-aryldiazeno-3-pentafluorophenyl-1,2-dihydropyridazine-5,6-diones or 6-aryl-7,8,9,10-tetrafluoro-2-phenyl-2,4a,6,10b-tetradropyridazo[4,3-c]cinnoline-3,4-diones, depending on the conditions. Cyclocondensation of ethyl 3-arylhydrazono-4-polyfluoroalkyl(or pentafluorophenyl)-2,4-dioxobutanoates with ethylenediamine led to 3-[1-arylhydrazono-2-oxo-2-polyfluoroalkyl(or pentafluorophenyl)ethyl]-5,6-dihydropyrazin-2(1H)-ones, and 3-[1-arylhydrazono-2-oxo-2-polyfluoroalkyl(pentafluorophenyl)ethyl]benzoxazin-2-ones were formed in the condensation with o-aminophenol. Pentafluorophenyl-substituted heterocycles were found to undergo intramolecular ring closure to give 3-hetaryl-substituted 1-aryl-5,6,7,8-tetrafluoro-1,4-dihydrocinnolin-4-ones. The reactions of ethyl 3-arylhydrazono-4-pentafluorophenyl-2,4-dioxobutanoates with o-aminobenzenethiol gave 3-[7-(2-aminophenylsulfanyl)-1-aryl-5,6,8-trifluoro-4-oxo-1,4-dihydrocinnolin-3-yl]benzothiazin-2-ones; 8a-hydroxy-11,12,13,14-tetrafluoro-10-(4-methoxyphenyl)-2,3,4,5,6,7,8a,10-octahydropyrazino[1′,2′:4,5][1,4]diazepino[6,7-c]cinnolin-8-one was isolated in the condensation of ethyl 3-(4-methoxyphenylhydrazono)-4-pentafluorophenyl-2,4-dioxobutanoate with N-(2-aminoethyl)ethane-1,2-diamine.     

Reactions of adamantyl-substituted keto esters with hydrazine and phenylhydrazine

Reactions of adamantyl-substituted keto and diketo carboxylic acid esters with hydrazine and phenylhydrazine were studied. Ethyl 3-(1-adamantyl)-2-(1-adamantylcarbonyl)-3-oxopropanoate reacted with hydrazine to give ethyl 3,5-di(1-adamantyl)-1H-pyrazole-4-carboxylate. Reactions of ethyl 2-(1-adamantylcarbonyl)-3-oxobutanoate and ethyl 4-(1-adamantyl)-3-oxo-2-(1-oxoethyl)butanoate with hydrazine and phenylhydrazine followed a complicated pattern and led to the formation of mixtures of the corresponding hydrazides and pyrazolones.     

1β-Methylcarbapenem intermediates via the thiolysis of a Meldrum's precursor

5-{3-[1-(tert-Butyldimethylsilyloxy)ethyl]-4-oxo-azetidin-2-yl}-2,2,5-trimethyl-[1,3]dioxane-4,6-dione (3) has been submitted to nucleophilic attack with various nucleophiles. Meldrum's moiety transesterification, C4-substitution, β-lactam ring opening and Meldrum's moiety decarboxylation were observed. Reaction of 3 with ethanethiol and dimethylaminopyridine in ethanol quantitatively furnished ethyl 2-{3-[1-(tert-butyldimethylsilyloxy)ethyl]-4-oxo-azetidin-2-yl}-thiopropionate as the 1:1 mixture of β (7a) and (8a) diastereoisomers.     

Novel 1,4-dihydropyridine calcium antagonists. II. Synthesis and antihypertensive activity of 3-[4-(substituted amino)phenylalkyl]ester derivatives

Novel 1,4-dihydropyridine derivatives bearing 3-[4-(substituted amino)phenylalkyl]ester side chains were prepared and tested for their antihypertensive activity in spontaneously hypertensive rats. Most compounds showed a more potent antihypertensive effect and a longer duration of action than nicardipine. The derivatives with a benzhydrylpiperazinyl and a benzhydrylpiperidinyl group were distinctive. 2-[4-(4-Benzhydryl-1-piperazinyl)phenyl]ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (4e), its 4-(4-cyano-2-pyridyl) analogue (4f), its 3-[4-(4-benzhydryl-1-piperazinyl)phenyl]propyl ester analogue (4h), its 2-[4-(4-benzhydryl-1-piperidinyl)phenyl]ethyl ester analogue (4j), and its 2-[4-(1-benzhydryl-4-piperidinyl)phenyl]ethyl ester analogue (4k) were selected as candidates for further pharmacological investigations.     

Preparation of aminotriazole-thione derivatives from n-aryl-n-carboxyethyl-β-alanines

Depending on the substituents in the aryl moiety, the fusion of N-aryl-N-ethoxycarbonyl-β-alanines with thiocarbohydrazide gives di- or monotriazole derivatives, namely, 4-amino-(2-{[2-(4-amino-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]anilino}ethyl)-4,5-dihydro-1H-1,2,4-triazole-5-thiones, 1-[2-(4-amino- 5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]-2,3-dihydroquinolin-4(1H)-ones, 4-amino-3-[2-(4-methylanilino))ethyl]-4,5-dihydro-1H-1,2,4-triazole-5-thione and 4-amino-3-[2-(4-ethoxyanilino)-ethyl]-4,5-dihydro-1H-1,2,4-triazole-5-thione. A ditriazolethione derivative was also obtained from the diethyl ester of N-ethoxycarbonyl-N-(4-ethoxyphenyl)- β-alanine.     

Synthesis of phenylacetylene containing 1,2,3-triazole group

Bromination of (E)-1-[4-(2-carboxy-vinyl)phenyl]-[1,2,3]triazole-4-carboxylic acid ethyl ester, which was synthesized in 90% yield by a Huisgen-type [3 + 2]-cycloaddition reaction between 3-(4-azidophenyl) acrylic acid and ethyl propiolate, in CHCl₃ followed by a debrominative decarboxylation reaction with Et₃N in DMF under microwave irradiation condition afforded stereoselective (Z)-1-(4-(2-bromovinyl)phenyl)-1,2,3-triazole-4-carboxylic acid ethyl ester in 94% yield. Treatment of (Z)-1-(4-(2-bromovinyl)phenyl)-1,2,3-triazole-4-carboxylic acid ethyl ester with EtONa in DMF afforded 1-(4-ethynylphenyl)-1,2,3-triazole-4-carboxylic acid ethyl ester in a yield of 90%.