头孢克肟中间体合成工艺的改进研究

对头孢克肟中间体2-(2-氨基-4-噻唑基)-2-[[(Z)-(叔丁氧羰基)甲氧]亚胺基]乙酸-2-苯并噻唑硫酯(1)的合成工艺进行了改进研究,即以廉价的乙酰乙酸甲酯为原料,经溴化、亚硝化、环合、醚化、水解、硫酯化6步反应制备1,总收率17.9%。其中2-(2-氨基-4-噻唑基)-2-(Z)-羟亚胺基乙酸甲酯采用了一锅合成法,简化了操作。     

噻虫胺的合成工艺优化

以2-氯-5-氯甲基噻唑与1,5-二甲基-2-硝基亚胺基-全氢-1,3,5-三嗪为原料,采用分解中间体1-(2-氯噻唑-5-甲基)-2-硝基亚胺基-3,5-二甲基-六氢-1,3,5-三嗪制备噻虫胺。对噻虫胺的合成工艺进行优化,通过研究得最佳工艺条件。创新性的加入吸水剂,噻虫胺产品纯度达96%,收率达82%,对产品进行了NMR,HPLC-MS及IR表征。此工艺选择性高、条件温和、原料易得、产品纯度高、收率高、适合工业化生产。     

一种头孢地尼侧链酯的制备方法

以(Z)-2-(2-氨基-4-噻唑基)-2-羟基亚胺乙酸乙酯和三苯基甲醇为原料,在碳酸二甲酯溶剂和碳酸二甲酯三氟化硼络合物催化下进行反应,反应完全后减压蒸去溶剂,加甲醇固化析晶,中间产物用片碱水解脱去乙酯,盐酸酸化,得到2-(2-氨基-4-噻唑)-2-(Z)-三苯基甲氧亚胺基乙酸。2-(2-氨基-4-噻唑)-2-(Z)-三苯基甲氧亚胺基乙酸与二硫化二苯骈噻唑,在亚磷酸三乙酯和三乙胺催化下进行酯化得到(Z)-硫代苯骈噻唑-2-(2-氨基-4-噻唑)-三苯甲基氧亚胺基乙酸活性酯,总收率为80.4%。方法操作简单,溶媒低毒易回收,成本低,得到产物纯度高,具有工业化生产前景。     

合成2-(2-氨基-4-噻唑)-2-(甲氧羰基甲氧亚胺基)乙酸顺反异构体的研究

以4-氯代-2-甲氧羰基甲氧亚胺基-3-氧代丁酸(CMOBA)为原料,通过控制反应体系的pH值,分别合成出高选择性的顺式2-(2-氨基-4-噻唑)-2-(甲氧羰基甲氧亚胺基)乙酸(简称(MICA)及反式MICA产物,用高效液相色谱、熔点和红外光谱对产物的结构和纯度进行了分析。并对形成顺、反异构体的机理进行了探讨。     

2-甲硫基-2-噻唑啉合成工艺研究

替比培南酯是目前唯一一个可以口服的碳青霉烯类抗生素,2-甲硫基-2-噻唑啉是替比培南侧链中间体,2-甲硫基-2-噻唑啉质量是影响替比培南侧链关键因素; 2-甲硫基-2-噻唑啉合成以2-巯基-2-噻唑啉为起始原料,甲醇为溶剂,碳酸钾作为缚酸剂,选用碘甲烷为经典甲基化试剂;反应温度25～30℃;反应时间4. 5 h最好;收率99%,纯度大于99%;操作简单,适合工业化生产。     

2-芳基-4-氰基亚胺基-1,3-噻唑烷类化合物的合成、结构和生物活性

以芳香醛、浓氨水、巯基乙酸为原料,经缩合、硫代、烷基化和胺解反应,合成了7个新的2-芳基-4-氰基亚胺基-1,3-噻唑烷类化合物.所有化合物的结构均经1H NMR和元素分析确证.初步生物活性试验结果表明:部分标题化合物具有一定的杀菌活性和促进黄瓜子叶生根活性.     

(Z)-2-(呋喃-2-基)-2-甲氧亚胺基乙酸合成研究进展

(Z)-2-(呋喃-2-基)-2-甲氧亚胺基乙酸是一种重要的医药中间体,主要用于合成头孢菌素-头孢呋辛(头孢呋辛钠或头孢呋辛酯)。按照不同的合成原料、试剂和反应路线对(Z)-2-(呋喃-2-基)-2-甲氧亚胺基乙酸的合成方法进展进行了综述。     

5-氯-2-甲基-4-异噻唑啉-3-酮的合成

以多硫化钠、丙烯酸甲酯、甲胺等为原料合成杀菌剂5-氯-2-甲基-4-异噻唑啉-3-酮,具有很好的杀灭细菌、霉菌的能力。     

生物素中间体:四氢-7-乙氧羰基-3,3-五亚甲基-5-硫代-1-戊基-3H,5H-咪唑并[1,5c]噻唑的合成

以正庚醛为起始原料 ,α 溴化后与环己酮、氨、硫氢化钠反应合成 2 ,2 五亚甲基 5 戊基 3 噻唑啉 ,再用三氟化硼催化后 ,与异硫氰基乙酸乙酯的锂衍生物反应合成生物素中间体四氢 7 乙氧羰基 3 ,3 五亚甲基 5 硫代 1 戊基 3H ,5H 咪唑并 [1,5c]噻唑 ,收率达 17 1% ,通过 3步反应建立了生物素的立体化学骨架     

2-氨基-4-氯-5-醛基噻唑合成工艺

以氯乙酸和硫脲为原料合成了2-亚氨基噻唑-4-酮,再与Vilsmeier试剂作用,经缩合水解得到2-氨基4-氯-5-醛基噻唑,总收率达到86％。     

Dithiocarbamate as an efficient intermediate for the synthesis of 2-(alkylthio)thiazol-4(5H)-ones

An effective approach for the synthesis of 2-(alkylthio)thiazol-4(5H)-ones from alkyl dithiocarbamates and chloroacetyl chloride in the presence of NaHCO₃ has been developed. Good to excellent yields of products, simple reaction conditions and general applicability are the most important advantages of this protocol.     

Preparation and Investigation of Novel PVA/Silica Nanocomposites with Potential Application in NLO

This research describes the synthesis of organomodfied sillica nanoparticles (NP)s /polyvinyl alcohol (PVA) nanocomposites (NC)s through consecutive three-steps. In the first step the surface modifier, namely 1-(benzo[d]thiazol-2-yl)-3-(3-(triethoxysilyl)propyl)urea, was prepared from the reaction of benzo[d]thiazol-2-amine and 3-isocyanatopropyl triethoxysilane. With success in the first step, the surface modifications of silica NPs were achieved by sol-gel procedure and at the final step, the preparation of PVA/silica NCs were targeted. The optical properties and morphology of the NPs and NCs were characterized. This investigation clearly showed that the new coupling agent could effectively prevent the agreggation of NPs.     

An efficient one-pot four-component Gewald reaction: Synthesis of substituted 2-aminothiophenes with coumarin–thiazole scaffolds under environmentally benign conditions

An elegant and efficient method has been outlined for the synthesis of novel 5-amino-4-[4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl]-3-arylthiophene-2-carbonitriles employing a one-pot four-component reaction of various aldehydes, 2-[4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl]acetonitrile, malononitrile and molecular sulfur independently in the presence of L-proline as a catalyst, under green reaction conditions. In an alternative approach, initially, the Knoevenagel condensation of these various aldehydes has been carried out with active methylene compounds malononitrile or 2-[4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl]acetonitrile to obtain the corresponding condensed compounds. These compounds then further subjected to a one-pot three-component Gewald reaction with molecular sulfur using sodium bicarbonate as a simple and inexpensive catalyst to obtain the target compounds. The effect of solvent and catalyst on these reactions has been screened to obtain the optimal conditions. The advantages of this protocol are the use of mild reaction conditions at ambient temperature, environmental friendliness, good yields in faster reaction times, convenient operation procedures, and broad substrate scope.     

New Pyrazine Conjugates: Synthesis,Computational Studies,and Antiviral Properties against SARS-CoV-2

Currently, limited therapeutic options are available for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We have developed a set of pyrazine-based small molecules. A series of pyrazine conjugates was synthesized by microwave-assisted click chemistry and benzotriazole chemistry. All the synthesized conjugates were screened against the SAR-CoV-2 virus and their cytotoxicity was determined. Computational studies were carried out to validate the biological data. Some of the pyrazine-triazole conjugates ( 5 d – g ) and (S)-N-(1-(benzo[d]thiazol-2-yl)-2-phenylethyl)pyrazine-2-carboxamide 12 i show significant potency against SARS-CoV-2 among the synthesized conjugates. The selectivity index (SI) of potent conjugates indicates significant efficacy compared to the reference drug (Favipiravir).     

Androgen Receptor Antagonists and Anti-Prostate Cancer Activities of Some Newly Synthesized Substituted Fused Pyrazolo-, Triazolo- and Thiazolo-Pyrimidine Derivatives

A series of substituted pyrazole, triazole and thiazole derivatives (2–13) were synthesized from 1-(naphtho[1,2-d]thiazol-2-yl)hydrazine as starting material and evaluated as androgen receptor antagonists and anti-prostate cancer agents. The newly synthesized compounds showed potent androgen receptor antagonists and anti-prostate cancer activities with low toxicity (lethal dose 50 (LD₅₀)) comparable to Bicalutamide as reference drug. The structures of newly synthesized compounds were confirmed by IR, ¹H-NMR, ¹³C-NMR, and MS spectral data and elemental analysis. The detailed synthesis, spectroscopic data, LD₅₀ values and pharmacological activities of the synthesized compounds are reported.     

Copolymer of sucrose and naphthoquinone imine derivatives

Summary The purpose of the present work was to prepare a macromolecular prodrug with methacrylic esters of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone-4-imine(I) and those of suorose. The copolymer IV obtained by a bulk copolymerization reaction was purified by GPC and characterized by infrared spectroscopy, differential scanning calorimetry and hydrolysis studies. Its alkaline hydrolysis led to compound I which exhibited trypanocidal activity against T.cruzi.     

Nitriles in heterocyclic synthesis: A new approach for the Synthesis of Thiazole derivatives

The reaction of 4-bromo-3-oxo-butyranilide ( 1 ) with KSCN afforded the thiocyanato derivative 2 . 2-Dicyanomethylthiazol-4-yl-acetanilide ( 3 ) was synthesised by reaction of 2 with malononitrile. A variety of substituted thiazol-2-yl malononitriles were prepared by reaction of 3 with hydroxylamine hydrochloride, phenylhydrazine and cinnamonitrile derivatives. The structure assignments of the new compounds are based mainly on ¹³C and ¹H-n.m.r. spectroscopic data.     

苯胺-β-亚胺/PdCl_2催化下的Suzuki偶联反应

选择溴苯与苯硼酸为模型反应,研究四种苯胺-β-亚胺配体/PdCl2催化下的Suzuki偶联反应。并考察了溶剂、碱等因素对该交叉偶联反应收率的影响。结果显示目标产物收率在配体具有较小的刚性,溶剂为甲醇/水,碱为K2CO3时最高（96.5%）。     

头孢三嗪反式异构体合成研究

以头孢主环(6R,7R)-7-氨基-8-氧代-3-[[(1,2,5,6-四氢-2-甲基-5,6-二氧代-1,2,4-三嗪-3-基)硫代]甲基]-5-硫代-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸(7-ACT)为起始原料,与反式活性酯侧链(E)-2-(2-氨基-4-噻唑基)-2-甲氧亚胺-乙酸-2-苯并噻唑硫酯(E-AE)反应作用生成(6R,7R)-7-[2-(2-氨基-4-噻唑基)-(E)-2-(甲氧亚胺)乙酰氨基]-8-氧代-3-[(1,2,5,6-四氢-2-甲基-5,6-二氧代-1,2,4-三嗪-3-基)硫代〗甲基]-5-硫代-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸,然后在丙酮溶液中与异辛酸钠成盐而制得反式头孢三嗪钠。该产品具有良好的稳定性与高纯度,可作为对照品使用。     

Synthesis,Spectroscopy and Tautomeric Study of Thiazoles substituted in positions 2 and 4 by hydroxy,mercapto and amino groups

Thiazoles substituted in positions 2 and 4 by hydroxy, mercapto and amino groups were synthesized, as well as its carbamate derivates and formylhydrazones. The research of the reaction of the formylhydrazide with 4-imino-2-thiazolidinone has not given the pyrazolo [3,4-d]- thiazol-2-one, but the 4-formylhydrazono-2-thiazolidine. The detailed tautomeric study of each of the heterocyclic compounds has been carried out by infrared spectroscopy, nuclear magnetic resonance of proton and of 13-carbon, and of masses.