2-异丙基-1,3-二氢-4(1H)异喹啉酮及其衍生物的合成

报道了异喹啉酮与格氏试剂反应合成四氢-4-羟基异喹啉酮化合物,NBS和混酸(HNO~3/HAc)与异喹啉酮反应合成异喹啉酮衍生物。6个新化合物的结构,通过元素分析,红外光谱和核磁共振氢谱,质谱给予证实。     

通过异喹啉盐与环状1,3-二酮一锅合成二氢异喹啉-3-酮-1,4-桥环结构

异喹啉盐具有两个亲电位点, 用它与双亲核试剂发生去芳构化/环化反应, 是高效构建异喹啉桥环结构的有效策略. 然而, 这一策略主要集中在1,3-桥环结构的合成. 最近利用异喹啉盐与4-羟基香豆素反应, 首次实现了二氢异喹 啉-3-酮-1,4-桥环的合成. 但是, 当用环状1,3-二酮代替4-羟基香豆素反应时, 意外地得到了异喹啉-1,3,4(2H)-三酮. 利用高分辨质谱分析发现, 这一意外转化是由于环状1,3-二酮发生O-亲核取代后, 消除2-溴-1,3-环状二酮, 得到4-溴异喹啉-3(2H)-酮. 该中间体发生两次连续水解/空气氧化后, 得到了异喹啉-1,3,4(2H)-三酮. 基于此机理的认识, 向反应体系中添加催化量的三氟甲烷磺酸后, 成功抑制了环状1,3-二酮的O-亲核取代反应, 顺利得到了二氢异喹啉-3-酮的1,4-桥环结构(33个反应实例). 反应条件温和, 提供了一种构建异喹啉1,4-桥环骨架的高效合成方法.     

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。     

1-甲基-5,6,7,8-四氢异喹啉酮-4-甲胺的合成研究

以环己酮为起始原料,经缩合、酰化及酸性水解反应制得2 乙酰基环己酮（1）;在三乙烯二胺催化下,1与氰基乙酰胺环化得四氢异喹啉酮（2）和四氢喹啉酮（3）混合物,在乙醇中回流并趁热过滤进行分离纯化得2和3; 2经催化加氢反应合成1-甲基-5,6,7,8-四氢异喹啉酮-4-甲胺,3步总收率39.8%,其结构经¹H NMR、¹³C NMR、 ¹H-¹⁵N HMBC和MS确证。     

2-异丙基-3-乙氧甲酰基-1,2,3,4-四氢异喹啉-4-酮衍生物的合成

报道了利用3-乙氧甲酰基异喹啉-4-酮分别与胍、脒、脲及硫脲类化合物缩合 反应合成异喹啉并嘧啶衍生物，邻氨基苯甲醛、邻氨基胡椒醛分别与异喹啉-4-酮 反应合成异喹啉并喹啉化合物．6个新化合物的结构通过元素分析、红外光谱、核 磁共振氢谱和质谱予以证实．     

5-羟基-3,4-二氢异喹啉-1-酮的合成

以异喹啉为起始原料,经成盐、磺化得异喹啉-5-磺酸(3),3与熔融的氢氧化钠和氢氧化钾反应得1,5-二羟基异喹啉(4),以5%Pd-C为催化剂还原4得5-羟基-3,4-二氢异喹啉-1-酮(1),总收率47.6%。1的结构经1H NMR和MS确证。     

1-(2-炔丙基)-7,8-二氢喹啉-2,5(1H,6H)-二酮的合成

以1,3-环己二酮为原料,依次经亚胺化反应、Michael加成-环化反应、烷基化反应合成了含有端基炔的喹啉酮衍生物——1-(2-炔丙基)-7,8-二氢喹啉-2,5(1H,6H)-二酮,其结构经1H NMR,HR-MS和2D NMR确证。     

含3,4-二氢-2(1H)-喹啉酮结构查尔酮衍生物的合成及蛋白酪氨酸磷酸酯酶1B抑制活性研究

蛋白酪氨酸磷酸酶1B(PTP1B)作为胰岛素和瘦素信号转导通路的负调节因子,已成为治疗糖尿病和肥胖症的潜在靶标.为了寻找非磷酸酯类PTP1B抑制剂,设计、合成了一系列含3,4-二氢-2(1H)-喹啉酮结构的新型查尔酮衍生物,并对化合物进行了PTP1B抑制活性测定.结果显示,所有化合物对PTP1B均显示出较强的抑制活性,其中化合物(E)-6-{4-[3-(4-氯苯基)-3-氧代-1-丙烯基]苄氧基}-3,4-二氢-2(1H)-喹啉酮(4e)和(E)-6-{4-[3-(3-溴苯基)-3-氧代-1-丙烯基]苄氧基}-3,4-二氢-2(1H)-喹啉酮(4i)活性最佳,IC50分别为(4.64±0.38)和(4.36±0.41)μmol/L.     

手性1-芳基四氢异喹啉类衍生物的合成新方法

以1,2,3,4-四氢异喹啉为原料,先依次与二碳酸二叔丁酯、亚氯酸钠反应得到N-Boc-1,2,3,4-四氢-1-异喹啉酮,再和芳基格氏试剂反应得到分子内不对称还原胺化反应的底物,最后以ax-Josiphos为手性配体,[Ir(COD)Cl]₂为金属前体,在Ti(OⁱPr)₄和40%HBr溶液组成的催化体系中合成了8个手性1-芳基四氢异喹啉类化合物,其结构经¹H NMR和¹³C NMR表征。该路线提供了一种以廉价1,2,3,4-四氢异喹啉为原料高效合成手性1-芳基四氢异喹啉类衍生物的新方法,为索利那新等药物的合成提供了新路径。      

6-芳基茚并异喹啉酮衍生物的合成新方法

设计了6-芳基茚并异喹啉酮衍生物的合成新方法.该方法运用立体选择性反应策略,专一性地得到cis-中间体:cis-N-(4-羟基苯基)-1-氧代-3-苯基-1,2,3,4-四氢异喹啉-4-羧酸;选择以KAl(SO4)2·12H2O为催化剂,高酞酸、对氨基苯酚、苯甲醛三组分一锅法反应得到6-芳基茚并异喹啉酮母核,最终以总收率36%~51%得到6-芳基茚并异喹啉酮衍生物,比原方法的平均收率提高15%左右,新方法具有立体选择性好、操作简化、收率高等优点,适宜大量制备.     

3-N-乙酰基-2-芳基-5-苯基-1,3,4-噁唑啉类化合物的合成与表征

以自制的苯甲酰腙与乙酸酐环合,高收率地合成了3-N-乙酰基-2-芳基-5-苯基-1,3,4-噁唑啉类化合物。其结构经^1H NMR,IR,MS和元素分析表征,并对其质谱碎片裂解途径进行了探讨。     

Synthesis of Newly Substituted Pyrazoles and Substituted Pyrazolo[3,4‐b]Pyridines Based on 5‐Amino‐3‐Methyl‐1‐Phenylpyrazole

The reaction of the aminopyrazole 1 with benzenesulfonyl chloride, arenediazonium salt, chloroacetyl chloride, ethoxy methyleneamlononitrile and with ethyl 2‐cyano‐3‐ethoxyacrylate gave the substituted 3‐methyl‐1‐phenylpyrazole 2–5a,b . Compound 5b was cyclized to 6 and to 7 by treating it with AlCl₃ and with POCl₃, respectively. Compound 6 converted to 7 by boiling it in POCl₃/PCl₅. Compound 10b was produced through reaction of 9 with acetophenone. Reaction of 1 with benzylidinemalononitrile afforded 11 . New methods for preparation of 15 and 16 are described. The reaction of 8 with malononitrile, thiosemicarbazide, phenyl hydrazine and acetophenone afforded compounds 18–21 . The reaction of 21 with malononitrile gave 22 . Compounds 23–26 were produced upon reaction of 10a with malononitrile, phenyl hydrazine, thiosemicarbazide, semicarbazide and with benzaldehyde, respectively.     

2—甲基—3—喹啉酸乙酯衍生物的合成

本文报道由化合物(1)经缩合、水解等反应合成10种新化台物,反应式如下:     

吡啶基三唑功能化罗丹明化合物的合成

以2-溴甲基吡啶氢溴酸盐和叠氮化钠为原料,合成中间体2-叠氮甲基吡啶（1）;对羟基苯甲醛和溴丙炔经取代反应合成中间体4-（丙-2-炔基丙氧基）苯甲醛（2）; 2与1经点击反应制得关键中间体BPT（3）; 3与罗丹明B酰肼经还原胺化反应得罗丹明类荧光探针,其结构经¹H NMR, IR和元素分析表征。     

苏型-N-苯甲酰基-3-苯基异丝氨酸甲酯的合成

紫杉醇;苏型-N-苯甲酰基-3-苯基异丝氨酸甲酯的合成     

Efficient access to some new pyrimidine derivatives and their antimicrobial evaluation

1-[4-(3-Hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl]ethanone ( 1 ) was used as a precursor for heterocyclic synthesis. Condensation of compound 1 with monochloroacetic acid and benzaldehyde gave thiazolopyrimidine 2 which in turn underwent cyclization with malononitrile dimmer to afford malononitrile derivative 3 . Also, the reaction of compound 1 with benzaldehyde under a basic condition produced chalcone 4 . Chalcone 4 can be used as a key intermediate for further preparation of heterocyclic compounds. In addition, compound 1 was allowed to react with malononitrile dimmer and/or ethyl chloroacetate to give pyrimidines 8 and 9 , respectively. Alkylation of compound 8 with ethyl chloroacetate afforded S-alkylated product 10 which was treated with hydrazine hydrate to yield the hydrazino derivative 11 . Alternative synthesis of compound 10 was taken place through reaction of compound 9 with malononitrile dimmer. The biological activity of the synthesized compounds was investigated. Compounds 1 , 4 , 5 , and 8 recorded high activities against Gram positive bacteria (S. aureus). Structures of the new synthesized compounds were elucidated by elemental analysis and spectral data.     

两种季铵盐型离子液体钯配合物的合成

以苯甲酰肼和4-醛基吡啶为原料,经过缩合反应制备亚胺型化合物1,分别与苄氯和对二苄氯结合制备了两个新型的离子液体型亚胺配体2和3,配体2和3分别与醋酸钯反应得到新型离子液体型钯配合物4和离子液体型自组装钯配合物5,其结构经¹H NMR,¹³C NMR,IR和MS确证。      

The molecular structure and chemical reactivities of the condensation products of o-substituted benzylidenacetylacetone with hydrazine dihydrochloride

Reaction of o-nitrobenzylideneacetylacetone ( 1a ) with hydrazine dihydrochloride in methanol gave 4-(α-methoxy-o-nitrobenzyl)-3,5-dimethylpyrazole hydrochloride ( 4a ), whose structure was unambigously confirmed by an X-ray crystallographic analysis, via 4-(o-nitrobenzylidene)-3,5-dimethylisopyrazole ( 2a ). Compound 2a was synthesized by condensation of 1a with hydrazine dihydrochloride in acetonitrile. Analogously the corresponding o-chloro derivatives ( 2b, 4b ) were obtained. These were converted to N-methyl ( 6b ) and N-acetyl ( 7a,b ) derivatives and the behaviors on bromination and pyrolysis were investigated.     

Synthesis,characterization, and biological activities of some novel thienylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines and related heterocycles

3-Cyano-5-ethoxycarbonyl-6-methyl-4-(2′-thienyl)-pyridine-2(1H)-thione ( 1 ) is synthesized and reacted with chloroacetamide or chloroacetonitrile to give 3-amino-5-ethoxycarbonyl-6-methyl-4(2′-thienyl)-thieno[2,3-b]pyridine-2-carboxamide 3a or its 2-carbonitrile analog 3b , respectively. Cyclocondensation of 3a with triethylorthoformate produced the corresponding pyridothienopyrimidineone 4 , which on heating with phosphorus oxychloride gave 4-chloropyrimidine derivative 5 . Compound 5 was used as key intermediate for synthesizing compounds 6 , 9 , 10 , 11 , and 12 upon treatment with some nucleophilic reagents such as thiourea, 5-phenyl-s-triazole-3(1H)-thione, piperidine, morpholine, or hydrazine hydrate, respectively. Reaction of pyridothienopyrimidinethione 6 with N-(4-tolyl)-2-chloroacetamide or ethyl bromoacetate afforded the corresponding S-substituted methylsulfanylpyrimidines 7 or 8 . The condensation of 3b with triethylorthoformate gave azomethine derivative 13 , which was reacted with hydrazine hydrate to give ethyl 3-amino-3,4-dihydro-4-imino-7-methyl-9-(2′-thienyl)pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine-8-carboxylate ( 14 ). Compounds 12 and 14 were used as precursors for synthesizing other new thienylpyridothienopyrimidines as well as isomeric thienyl-s-triazolopyridothieno- pyrimidines. All synthesized compounds were characterized by elemental and spectral analyses such as IR, ¹H NMR, and ¹³C NMR. In addition, majority of synthesized compounds were tested for their antifungal activity against five strains of fungi. Moreover, compounds 3a , 5 , 6 , 8 , and 22 were screened for their anticancer activity against HEPG-2 and MCF-7 cell lines.     

Facile Novel Synthesis and Reactions of Thiazolidin-4-one Derivatives for Antimicrobial Agents

A facile and fast procedure for synthesis of 3-phenyl-cyclohexane(1′-2)thiazolidin-4-one (1), which underwent condensation with glucose and p-chlorobenzaldehyde to afford 2 and 3, respectively. Compound 3 was used as precursor for the preparation of some fused heterocyclic compounds 4–7. Compound 4 was alkylated using dichloroacetone and chloroacetic acid to afford 8 and 9, respectively. Also, it reacted with acrylonitrile and hydrazine hydrate to afford 10 and 11, respectively. Compound 9 was condensed with p-chlorobenzaldehyde and glucose to afford 12 and 13, respectively. Selected members of the synthesized compounds were screened for antimicrobial activity.