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。     

KF-alumina催化下2-氨基-4-芳基-5,6-二氢化-4H-P比喃[3,2-c]喹啉-5-酮-3-羧酸酯衍生物的一步合成

以芳醛、氰乙酸酯和4-羟基喹啉-2-酮为原料，乙醇为溶剂，在KF—Al2O3催化下80℃，一步合成了2-氨基-4-芳基-5，6-二氢化-4H-吡喃[3，2-c]喹啉-5-酮-3-羧酸酯衍生物，和其它方法相比，具有反应条件温和，容易操作和产率高等优点，产物4a的结构通过X单晶衍射分析确证．     

KF-alumina 催化下2-氨基-4-芳基-5,6-二氢化-4H-吡喃[3,2-c]喹啉-5-酮-3-羧酸酯衍生物的一步合成

以芳醛、氰乙酸酯和4-羟基喹啉-2-酮为原料, 乙醇为溶剂, 在KF-Al₂O₃催化下80 ℃, 一步合成了2-氨基-4-芳基-5,6-二氢化-4H-吡喃[3,2-c]喹啉-5-酮-3-羧酸酯衍生物, 和其它方法相比, 具有反应条件温和, 容易操作和产率高等优点, 产物4a的结构通过X单晶衍射分析确证.     

脯氨酸催化新型3-α,β-不饱和酮取代-4-羟基喹啉-2-酮简便合成及其荧光性质研究

3-乙酰-4-羟基喹啉-2-酮和芳香醛在L-脯氨酸有效催化下发生Aldol反应,生成一系列缩合产物3-α,β-不饱和酮取代-4-羟基喹啉-2-酮.该反应在甲醇溶液中进行,并且产物作为沉淀直接从溶液中析出,简单洗涤可得纯产物.研究表明芳香醛上的取代基性质对产物的产率有显著影响,其结果证实了该缩合反应经历了一个脱水中间体的反应历程.此外,对产物的荧光性质研究表明该类化合物可作为潜在应用价值的有机光学材料.     

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.     

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。     

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.     

由N-苯基[1,3]苯并噁嗪正离子与烯烃[4+2]反应合成喹啉并[1,2-c][1,3]苯并噁嗪-6-酮衍生物

以BF3·OEt2 为催化剂, 在室温下通过4-羟基-N-苯基[1,3]苯并噁嗪-2-酮的脱羟基产生N-苯基[1,3]苯并噁嗪正离子, 然后与富电子烯烃发生Diels-Alder反应, 合成出了一系列喹啉并[1,2-c][1,3]苯并噁嗪-6-酮和喹啉并[1,2-c][1,3]萘并噁嗪-6-酮衍生物.     

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。     

KF/Al2O3催化下芳醛和4-羟基喹啉-2-酮的反应研究

以芳醛和4-羟基喹啉-2-酮为原料, 在KF/Al₂O₃催化下以乙醇为溶剂, 在80 ℃合成了一系列新的双(4-羟基-2-氧代喹啉-3-基)-芳基甲烷衍生物, 反应条件温和, 产率较高, 并通过IR, ¹H NMR和元素分析确证产物的结构.     

Excess heat capacities of mixtures containing 1-methylpyrrolidin-2-one,chlorotoluenes and benzene

Excess heat capacities, ${(C_P^E)}_{\mathit{ijk}}$ of {1-methylpyrrolidin-2-one (i) + benzene (j) + o- or m- or p-chlorotoluene (k)} and $C_P^E$ of their sub-binary {1-methylpyrrolidin-2-one (i) + benzene (j)}; {benzene (i) + m- or p-chlorotoluene (j)} mixtures have been determined using their measured heat capacities data at T = (293.15, 298.15, 303.15) K and 0.1 MPa using micro differential scanning calorimeter. The results are discussed in terms of Graph (which deals with the topology of the constituent molecules) theory. The results suggest that $C_P^E$ and ${(C_P^E)}_{\mathit{ijk}}$ values commuted by Graph theory compare well with experimental values.     

Quantum-chemical Studies of Pyrimidin-4-ones. 2. Stability in the Gas Phase of Tautomers of Pyrimidin-2,4-dione, 2-Thioxo-, 2-Selenoxo-, 2-Amino-, and 2-Acetylaminopyrimidin-4-ones, and Their 6-Methyl- and 6-Phenyl Derivatives

The relative stability in the gas phase and the most probable reaction centers for electrophilic attack for the tautomers of pyrimidin-2,4-dione, 2-thioxo-, 2-selenoxo-, 2-amino-, and 2-acetylaminopyrimidin-4-ones, and their 6-methyl- and 6-phenyl derivatives have been investigated on the basis of the results of quantum-chemical calculations, using the semi-empirical PM3 method, without taking solvent effects into account.     

Three-component condensation of pyridin-2-one, bis(2-chloroethyl)amine hydrochloride, and K2CO3 in DMF as a new method for oxazolidinylethylation

Three-component condensation of pyridin-2-one, bis(2-chloroethyl)amine hydrochloride, and K₂CO₃ in DMF unexpectedly gave N-and O-oxazolidinylethylation products of pyridin-2-one in the ratio 3: 2. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1047–1048, May, 2007.     

4-Hydroxyquinol-2-ones. 86. Synthesis of Methyl (Ethyl) Esters of 1-Substituted 4-Amino-2-oxoquinoline-3-carboxylic Acids

Several variants of the synthesis of esters of 1-N-substituted 4-amino-2-oxoquinoline-3-carboxylic acids have been studied, one of which is recommended as preparative. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1355–1361, September, 2005.     

4-Hydroxy-2-quinolones. 84. Synthesis of 5-R-5H-5,7a,12-Triazabenzo[a]anthracene-6,7-diones

2-Aminopyridines react under thermolysis conditions with ethyl 1-R-4-chloro-2-oxoquinoline-3-carboxylates exclusively in the imino form to give the corresponding 5-R-5H-5,7a,12-triazabenzo[a]anthracene-6,7-diones and 4-(pyridyl-2-amino)-1-R-quinolin-2-ones. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1060–1070, July, 2005.     

Conformation of α,α,α′-Trisubstituted Cyclododecanone

Ten α,α,α′-trisubstituted cyclododecanones were synthesized and characterized by elemental analyses, infrared, 1^H NMR and 13^C NMR spectra, and X-ray diffraction. NMR data could not give conformational information clearly, but some of their ring skeleton conformations of cyclododecanone moiety were showed to remain the unchanged [3333]-2-one conformation with little distortion, while the others were changed to the [3324]-2-one conformation in their crystal structures. These are consistent with the results of molecular mechanics calculation with Sybyl 6.9 software and Tripos force field, and semi-empirical quantum calculation with AM 1 method in Gaussian 98 software. Two geminal substituting groups are located at α-corner carbon atom, and the third group is at α-side-exo carbon atom in both conformations. Both [3333]-2-one and [3324]-2-one conformations are present in a dynamic equilibrium in the solution, but only one preferred conformation exists in the crystal solid.     

Reaction of 3(Z)-benzoylmethylidene-6-nitro-3,4-dihydro-2H-1,4-benzooxazin-2-one with oxalyl chloride

3(Z)-Benzoylmethylidene-6-nitro-3,4-dihydro-2H-1,4-benzooxazin-2-one reacts with (COCl)₂ as imino enol rather than enamino ketone. The reaction is accompanied by replacement of the hydroxy group by chlorine. The molecular and crystal structures of the starting 1,4-benzooxazin-2-one and its chlorinated derivative were studied by X-ray diffraction analysis.     

Short synthesis of 4-aryl-3-pyrrolin-2-ones

A three step, convergent synthesis of 4-aryl-3-pyrrolin-2-ones from a tetramic acid has been developed. The key transformation utilized a Suzuki-Miyaura cross-coupling reaction between a 4-tosyloxy-3-pyrrolin-2-one and an arylboronic acid. This work also provides access to 4-arylpyrrolidin-2-ones, cyclic analogs of γ-aminobutyric acid (GABA). Hydrogenation of 4-(4′-chlorophenyl)-3-pyrrolin-2-one proceeded smoothly to give baclofen lactam.