微波辐射合成N-(2-氯-1-氧-5-吡啶甲基)二甲酰亚胺类化合物和生物活性研究

以二甲酰亚胺钾3a～3g与2-氯-5-氯甲基吡啶的N原子氧化后得到的2-氯-1-氧-5-氯甲基吡啶发生亲核取代反应, 用传统和微波两种方法合成了7种未见文献报到的化合物N-(2-氯-1-氧-5-吡啶甲基)二甲酰亚胺类化合物4a～4g. 对比两种合成方法, 在常压下, 微波辐射作为反应热源具有用时少、环境友好、易纯化和产率高的特点. 这些目标化合物4a～4g的结构经元素分析结果, IR, GC-MS, ¹H NMR, ¹³C NMR确证. 初步的生物活性测定结果表明, N-(2-氯-1-氧-5-吡啶甲基)二甲酰亚胺类部分化合物具有良好的杀虫活性.     

N'-(4,6-二取代嘧啶-2-基)氧化烟酰硫脲的合成与生物活性测定

合成并表征了9种未见文献报道的N'-(4,6-二取代嘧啶-2-基)氧化烟酰硫脲衍生物3, 结构经IR, ¹H NMR, 元素分析得到确证. 初步的生物活性测试表明化合物3a具有较好的除草活性, 化合物3b具有一定的杀虫活性.     

微波作用下1-苯基-5-[5-(芳胺羰基甲硫基)-4-苯基-1,2,4-三唑-3-甲硫基]四唑的合成及生物活性

采用微波和相转移催化法通过1-苯基-5-(4-苯基-1,2,4-三唑-5-巯基-3-甲硫基)四唑(2)与2-氯乙酰芳胺(3)反应高效、快速地合成了10种尚未见文献报道的1-苯基-5-[5-(芳胺羰基甲硫基)-4-苯基-1,2,4-三唑-3-甲硫基]四唑. 其结构经 IR, ¹H NMR, ¹³C NMR 和元素分析表征. 生物活性实验结果表明, 该类化合物在较低浓度下部分化合物对小麦芽有很好的促进作用.     

4-(N-取代苯基)氨基喹唑啉类化合物的合成及抗磷酸化活性研究

以4-氯喹唑啉为起始原料, 经环化、氯化、取代三步反应, 合成了8个新的4-取代苯基氨基喹唑啉类化合物. 采用¹H NMR, ¹³C NMR, MS, IR及元素分析对目标化合物的结构进行了表征. 生物活性测试表明, 化合物1f在1 μmol• L^－1 浓度下对PC3细胞增殖抑制活性达到88.6%, 进一步研究表明该化合物具有较高的抑制细胞外信号调节激酶(ERK)磷酸化的活性.     

新型3-取代-6-(4-氯苯基)-7-(1H-1,2,4-三唑-1-基)-1',2',4'-三唑[3,4-b]-1",3",4"-噻二嗪衍生物的合成及抗菌活性

通过3-取代-4-氨基-5-巯基-1,2,4-三唑(3a～3m)和2-溴-2-(1H–1,2,4-三唑-1-基)-4′-氯代苯乙酮(2)的缩合反应, 合成了13个新型3-取代-6-(4-氯苯基)-7-(1H-1,2,4-三唑-1-基)-1',2',4'-三唑[3,4-b]-1",3",4"-噻二嗪衍生物4a～4m. 化合物结构经元素分析, ¹H NMR, IR和MS进行了表征. 抗菌试验表明所合成的化合物对细菌表现出中等程度的抑制活性.     

含氨基酸席夫碱的5-氟尿嘧啶衍生物的合成及其抗肿瘤活性

以N 1-(2-四氢呋喃烷基)-5-氟尿嘧啶为原料, 与1,4-二溴丁烷反应, 得到N¹-(2-四氢呋喃烷基)-N³-(4-溴丁基)-5-氟尿嘧啶(2), 最后与氨基酸席夫碱的钾盐缩合, 得到13个新的目标化合物3. 其结构经IR, ¹H NMR, MS和元素分析确证. 初步的体外抗肿瘤试验结果表明, 目标化合物具有一定的抗肿瘤活性.     

1-[5-(1,3-二氧-4,5,6,7-四氢-1H-异吲哚-2-基)苯基]-3-取代脲衍生物的合成与除草活性研究

为了寻找高效低毒的原卟啉原氧化酶抑制剂(protox)类除草剂, 设计并合成了一系列1-[5-(1,3-二氧-4,5,6,7-四氢-1H-异吲哚-2-基)苯基]-3-取代脲类衍生物4a～4d和5a～5g. 化合物4a～4d经异氰酸酯法合成, 收率、纯度高; 化合物5a～5g利用固体光气一锅法合成, 反应时间短.所得化合物结构经¹H NMR, IR, 质谱和元素分析表征. 初步生物活性测试表明: 化合物4c, 5a, 5b, 5c在有效成分75 g/hm² 剂量下对苘麻、马刺苋、凹头苋等双子叶杂草表现出90%以上的防效.     

5-[2-(8-羟基喹啉-2-基)乙烯基]-2-甲基-8-羟基喹啉的合成、抗氧化活性及促进鼠骨髓间质干细胞增殖的研究

设计合成了5-[2-(8-羟基喹啉-2-基)乙烯基]-2-甲基-8-羟基喹啉(5), 用IR, UV, ¹H NMR, MS和元素分析确认其结构. 利用DPPH•法和噻唑蓝比色法(MTT法)分别测定了目标产物的抗氧化活性及调控鼠骨髓间质干细胞(MSCs)增殖的作用. 结果表明, 目标产物有较强的抗氧化活性, 在低浓度时对鼠骨髓间质干细胞有促进作用.     

2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-5-(取代苯基亚甲基)-4- 噻唑啉酮的合成

以2-氨基-5-取代苯氧甲基-1,3,4-噻二唑(1)为起始原料, 合成了中间体2-氯乙酰氨基-5-取代苯氧甲基-1,3,4-噻二唑)-2-乙酰亚胺(2)和2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-4-噻唑啉酮(3), 化合物3进一步与取代苯甲醛发生类Knoevenagle缩合反应, 得到了一系列2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-5-(取代苯基亚甲基)-4-噻唑啉酮类化合物4a～4p. 目标化合物4a～4p的结构经IR, ¹H NMR和元素分析确证.     

2-取代苯基-5-(3,4,5-三甲氧基苯基)-1,3,4-噁二唑衍生物的合成及生物活性研究

合成了10个2-取代苯基-5-(3,4,5-三甲氧基苯基)-1,3,4-噁二唑衍生物. 并经过元素分析, IR, ¹H NMR, ¹³C NMR对其结构进行了确认. 初步生物活性测试表明, 部分化合物具有一定抗癌活性.     

Solvent-Free Green Synthesis of Azines and Their Conversion to 2,5-Disubstituted-1,3,4-thiadiazoles

A solvent-free, clean, and efficient method has been developed for the synthesis of 2,5-disubstituted-1,3,4-thiadiazoles via azines. This approach exploits the synthetic potential of clean reactions and offers many advantages such as excellent product yields, easy isolation of products, and ecofriendly benign reaction conditions. The newly synthesized compounds were analyzed by infrared, ¹H NMR, ¹³C NMR, and elemental analysis.     

Novel and Efficient Cyclization Procedure for the Synthesis of 2,5-Disubstituted-1,3,4-thiadiazoles Without Using Any Ring-Closing Reagents

A novel method for the synthesis of 2,5-disubstituted-1,3,4-thiadiazoles via direct ring closure of 1,6-disubstituted-2,5-dithioureas in dimethylformanide without using any ring-closing reagents has been accidentally discovered. Repeated and extended experiments confirmed that this is a very simple and efficient way to synthesize these kinds of fine chemicals. A series of novel 2,5-disubstituted-1,3,4-thiadiazoles have been synthesized via this method in good yields.     

酰基硫脲衍生物的合成、结构表征及生物活性研究

在超声波辐射下, 以PEG-400为固-液相转移催化剂, 用芳胺与双酰基异硫氰酸酯反应, 合成出了15种新的结构不对称的双酰基硫脲类化合物(6和6')和9种新的分子中含酰胺基团的单酰基硫脲类化合物(7和7'). 利用元素分析, IR, ¹H NMR, ¹³C NMR, APT, 1D NOE及2D NMR技术确定了所合成化合物6和6'及7和7'的结构, 并对它们NMR谱中低场C, H进行了归属. 杀菌、杀虫和除草活性筛选测定实验结果表明, 所测试化合物对瓜炭疽病菌均具有抑制作用, 其中6e抑制率最高, 达到62.4%; 目标化合物7a对黄瓜白粉病菌有一定的抑制作用. 单胺氧化酶活性测定实验表明：大部分目标化合物对单胺氧化酶具有一定的抑制活性, 其中浓度在1×10^－3 mol•L^－1时目标化合物6'c和6'd的抑制活性较强, 明显高于其它化合物. 目标化合物没有抗惊厥活性.     

超声波辐射固-液相转移催化下2,5-二取代-1,3,4-噻二唑和N-取代二酰肼的一锅法合成研究

采用超声波辐射与相转移催化联用技术, 4-甲基苯氧乙酰氯(4)和硫氰酸铵反应得到中间体芳氧乙酰基异硫氰酸酯5, 不经分离直接与芳氨基乙酰肼2反应, 一锅法制得了7个新的2,5-二取代-1,3,4-噻二唑7a～7g和9个新的N-取代二酰肼8a～8i, 并利用IR, ¹H NMR, ¹³C NMR, MS谱和元素分析对其结构进行了表征.     

Salts of 2,5-dimercapto-1,3,4-thiadiazole

Reaction of 2,5-dimercapto-1,3,4-thiadiazole with ammonia or pyridine gives monoammonium or monopyridinium slats, and the reaction with hydrazine hydrate gives both mono- and dihydrazine salts, which was confirmed by alkylation of the salts obtained. Difference in the chemical shifts of the SCH₂R groups was found in the¹H NMR spectra of the mono- and dialkyl-substituted 2,5-dimercapto-1,3,4-thiadiazoles.Institute of Chemistry, Vilnius LT-2600, LithuaniaTranslated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 682–687, May, 2000.     

One-pot synthesis of 2,5-disubstituted-1,3,4-thiadiazoles under ultrasonic irradiation

A facile one-pot synthesis of 2,5-disubstituted-1,3,4-thiadiazoles was achieved by ultrasonic irradiation of a mixture of 1- naphthylacetyl chloride,NH_4CNS,CH_2Cl_2 and PEG-400 for 1.5 h at 10-20℃and subsequent irradiation for 1.5h in the presence of N-arylglycine hydrazides.This method requires short time and gives thiadiazoles in high yields.     

5-Phenyl-2-(pyrazol-4-yl)-1,3,4-thiadiazoles

By recyclization of 2-R-6-ethyl-7-hydroxy(methoxy)-3-(5-phenyl-1,3,4-thiadiazol-2-yl)chromones when treated with hydrazine hydrate and phenylhydrazine, we synthesized 5-phenyl-2-(3-R-5-R1-1H-pyrazol-4-yl)-1H-1,3,4-thiadiazoles and 2-(3-R-5-R1-1-phenyl-1H-pyrazol-4-yl)-5-phenyl-1H-1,3,4-thiadiazoles. We confirmed the structure of the latter from ¹H NMR spectra.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 781–787, May, 2005.     

Synthesis and Characterization of New Thebaine Derivatives: 2-(6,14-endo-Ethenotetrahydrothebaine-7α;-yl)-5-(N-Arylamino)-1,3,4-Thiadiazoles

Abstract

We have synthesized a series of novel 2-(6,14-endo-ethenotetrahydrothebaine-7α-yl)-5-N-arylamino-1,3,4-thiadiazoles (5a–n) as potential narcotic analgesics, which are analogs of morphine. The synthesized compounds exhibit rigid morphine structures, including a 6,14-endo-entheno bridge and a 5-N-arylamino-1,3,4-thiadiazol-2-yl group at C-7 position that adopted S-configuration. The structures and stereochemistry of the compounds were completely assigned using one- and two-dimensional NMR experiments (¹H NMR, APT, COSY, NOESY, HMQC, and HMBC), FTIR, and high-resolution mass spectral (HRMS) data.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Synthesis,Reactions, and Anticancer Activity of Some 1,3,4-Thiadiazole/Thiadiazine Derivatives of Carbazole

A novel method for the synthesis of 1,3,4-thiadiazole and 1,3,4-thiadiazine derivatives bearing a carbazole moiety is described. Carbazole was transformed into carbazole-9-thiocarbohydrazide in two steps. This compound was allowed to react with various electrophiles to yield 1,3,4-thiadiazole derivatives. The reaction with bifunctional electrophiles led to 1,3,4-thiadiazines. 2-(Carbazol-9-yl)-5,6-dihydro-4H-1,3,4-thiadiazin-5-one reacted with piperidine and formaldehyde to yield the 4-(piperidin-1-ylmethyl) derivative. The reaction with aromatic aldehydes led to the corresponding 6-arylidene derivatives, which were transformed into pyrimidino[4,5-e]-1,3,4-thiadiazines and pyrazolo[3,4-e]-1,3,4-thiadiazines by a reaction with guanidine, acetamidine, or phenylhydrazine, respectively. Structures of the products were confirmed by ¹H NMR, ¹³C NMR, IR, and mass spectrometric measurements. Selected examples of products were screened for anticancer activity.