从磺酰氯合成亚磺酰胺

苯或对甲苯磺酰氯等在三苯膦（作还原剂）和三乙胺作用下与伯胺或仲胺在二氯甲烷中，0℃反应1h可得亚磺酰胺。30余例收率中等，个别较高或偏低。多数有副产物磺酰胺。     

降压药物的研究——苯駢噻二嗪类化合物的合成

为了寻找更有效的苯駢噻二嗉类的降压药物,合成了五个类型化合物共五十二个.(1)間位氯代苯胺与过量氯磺酸反应(另加三氯化磷),产生的双磺酰氯与氫氧化铵或脂族胺,芳香胺,脂环胺等作用可得到相应的双磺酰胺.間位三氟甲基苯胺先轉变成2-三氟甲基-4氨基-苯磺酸后再氯磺化、氨化可得到相应的双磺酰胺.苯胺經氯磺化、氨化得到三磺酰胺.(2)磺酰胺与脂族醛、芳香醛作用,縮合成苯駢噻二嗪类化合物.这些化合物不溶于水及酸而溶于碱,因此可利用此性质,进行化合物的純制.三磺酰胺与甲醛反应得到三环化合物,而与乙醛反应得苯駢噻二嗪衍生物.(3)双磺酰胺与酮也可进行縮合,但此醛类困难.     

1-烷基-6-氟-1,4-二氢-7-(4-酰基-1-哌嗪基)-4-氧代喹啉-3-羧酸类似物的合成及其抗菌活性

目的 设计合成具有广谱抗菌活性的含氟喹诺酮类化合物。方法 利用吡酮酸7位哌嗪基4位氮上存在的活性氢为反应修饰基点，与磺酰氯，酰氯，氯甲酸酯进行Schotten-Baumann酰基化反应设计合成一系列含有磺酰基、酰基和烷氧羰基类氟喹诺酮类似物。结果 合成了20个含有磺酰基、酰基和氧羰基的氟喹诺酮类似物，利用元素分析、核磁共振进行了结构确认。结论 合成了16个未见报道的新化合物，初步体外活性测试结果表明，其中的4个化合物有较高的生物活性。     

左氧氟沙星中间体苯并噁嗪的拆分

氧氟沙星的合成中间体苯并嗪［（±）１］先与（Ｓ）－Ｎ－对甲苯磺酰脯氨酰氯反应，经结晶分离，其母液（２ａ）水解后所得游离碱（１ａ）再与（１Ｓ）－（＋）－１０－樟脑磺酸成盐，重结晶后的盐（３）碱析得所需（Ｓ）－苯并嗪［（－）１］。     

2,2-二甲基-4-(2,5-二氟苯基)-5-[(4-氨基磺酰基)苯基]-3(2H)-呋喃酮的合成

用2,5-二氟苯乙酸与茴香硫醚经傅-克反应、与3-溴-3-甲基-2-氧代丁腈成环及硝酸氧化制得2,2-二甲基-4-(2,5-二氟苯基)-5-[(4-甲磺酰基)苯基]-3(2H)-呋喃酮(7),7与乙酐反应后再经过硫酸氢钾复合盐氧化、氢氧化钠水解得4-[2,2-二甲基-3-氧代-4-(2,5-二氟苯基)-3(2H)-呋喃-5-基]苯磺酸钠(9),最后依次与磺酰氯和氨水反应制得2,2-二甲基-4-(2,5-二氟苯基)-5-[(4-氨基磺酰基)苯基]-3(2H)-呋喃酮,总收率约46％.     

N2-(4-甲基苯磺酰基)-L-天冬酰胺的合成工艺

目的 探索N2-(4-甲基苯磺酰基)-L-天冬酰胺的最佳合成工艺.方法 以L-天冬酰胺与对甲苯磺酰氯为原料、水为溶剂,探索不同的缚酸剂,对反应收率的影响.结果 以水为溶剂、三乙胺为缚酸剂,于0～5℃反应3h,自然升至室温反应8h,过滤,调母液pH2,过滤得白色固体,用甲醇精制得目标物,收率80.2％.结论 该工艺稳定可行.     

磺酰氯和活性醇一锅法制备硫醚

芳基磺酰氯在氮气保护下先后与 Zn和二甲基二氯硅烷反应 ,还原成硫醇 ,不必分离 ,再加入苄醇或烯丙醇等反应生成相应的硫醚 ,13例收率 34%～ 87%。磺酰氯和活性醇一锅法制备硫醚@金卫东     

新一类氟喹诺酮药物—苯磺酰胺氟喹诺酮

概述了新一类的氟诺酮－－苯磺酰胺氟喹的研究进展,包括其合成、体外抗菌活性、构效关系分析、作用机制,并展望了苯磺酰胺氟喹诺酮的应用前景。     

有机合成文摘

S33- 75　新颖有效的酯化、酰胺化试剂—— Me2 NSO2 Cl(二甲胺基磺酰氯 )和 N,N-二甲胺　 Wakasugi K等 [Tetrahe-dron L ett,2 0 0 1.74 2 7]羧酸与等当量醇或胺在温和条件下 ,以二甲胺基磺酰氯(Me2 NSO2 Cl)和二甲胺催化 ,可高收率制得各种酯或酰胺。酯 15例收率 71%～ 96 % ;酰胺 7例收率 88%～ 97%。[朱雪焱摘 ]S33- 76　芳基砜的新制法　 Steensma RW等 [TetrahedronL ett,2 0 0 1,4 2 :2 2 81]芳基三氟甲基砜与格氏试剂于 THF中 ,室温或回流条件下反应 1h(2例 16 h) ,发生三氟甲基脱离 ,形成新的砜。收率除 1例 2 8%外 ,…     

4-苯磺酰氧基-苯并口恶唑酮衍生物的合成及其抗炎镇痛作用

目的合成天然产物4-取代苯并口恶唑酮衍生物并对其抗炎镇痛活性进行初步评价。方法以2-氨基间苯二酚为原料,与三光气缩合制得4-羟基-苯并口恶唑酮;以2-取代苯酚为起始物,经取代、重排、氧化反应得到取代苯磺酰氯,取代磺酰氯与4-羟基-苯并口恶唑酮反应制得4-苯磺酰氧基-苯并口恶唑酮酯类化合物。采用二甲苯致小鼠耳肿胀法和小鼠醋酸扭体法测定目标化合物的抗炎及镇痛活性。结果与结论共合成了11个目标化合物,其中10个化合物未见文献报道,目标化合物的结构经ESI-MS、1H-NMR、13C-NMR谱确证;活性实验结果显示,化合物5g具有一定的抗炎活性,化合物5a、5d、5j具有较好的镇痛活性。     

N-9-Fluorenylmethoxycarbonylpyroglutamate

Fmoc-glutamic acid is converted by thionyl chloride into the dichloride, which spontaneously cyclizes to Fmoc-pyroglutamyl chloride. The latter is stable to water. Pure Fmoc-pyroglutamyl chloride is obtained by washing the reaction mixture with water, which destroys uncyclized dichloride by converting it into the 2-alkoxy-5(4H)-oxazolone that is readily hydrolyzed. Fmoc-pyroglutamic acid and succinimidyl ester are obtained from the chloride by acid hydrolysis and reaction with N-hydroxysuccinimide, respectively.     

甲磺酸帕珠沙星注射液的过敏性与溶血性试验

目的:研究甲磺酸帕珠沙星注射液的过敏性与溶血性。方法:选用合格豚鼠与新西兰家兔分别对甲磺酸帕珠沙星注射液进行全身过敏试验和溶血性试验。结果:0.9%氯化钠注射液组、甲磺酸帕珠沙星注射液高、低剂量组豚鼠均无全身过敏反应症状,而10%新鲜鸡蛋清溶液对照组豚鼠因过敏反应在2 min内死亡,且各组豚鼠试验前后的体重无明显差异(P>0.05);溶血试验中甲磺酸帕珠沙星注射液各试管均无溶血现象发生,而对照管发生溶血。结论:甲磺酸帕珠沙星注射液无溶血性、无致敏性。     

乙酰阿魏酰氯合成工艺的优化

目的优化乙酰阿魏酰氯的合成工艺。方法先以香草醛和乙酸酐等为原料,经Perkin反应合成乙酰阿魏酸,进一步制备乙酰阿魏酰氯。按正交表L9(34)表设计考察乙酰阿魏酸和乙酰阿魏酰氯合成的影响因素,对乙酰阿魏酸合成中反应时间、PEG-400用量及投料比等因素进行优选,同时也考察乙酰阿魏酰氯合成的反应时间、反应温度及乙酰阿魏酸与氯化亚砜的摩尔比等因素对吸收率的影响。结果前者最佳工艺为A1B2C1,后者最佳工艺为A1B2C2,两步总收率达65%。结论该最佳工艺可缩短反应时间,提高生产效率,适合工业生产。     

D-青霉胺酰化消旋工艺及动力学研究

目的研究D-青霉胺在酸性条件下进行酰化外消旋的工艺。方法以D-青霉胺为原料,在醋酸溶液中,用乙酰氯为酰化试剂进行消旋化,得到了D-青霉胺酰化消旋物;并以溶剂量、反应温度、反应时间、乙酰氯的量等为因素考察最佳工艺条件;测定反应温度、时间与消旋过程比旋度的关系,计算酰化过程的动力学方程。结果得到最佳工艺条件即青霉胺量-醋酸量-乙酰氯量(1∶7∶2),反应温度80℃,反应时间5h。酰化过程的动力学方程符合一级线性关系。结论该工艺条件缓和,路线简单,为D,L-青霉胺的制备提供了直接原料。     

The cyclodesulphurization of thio-compounds. Part 15: Synthesis of 6-substituted aminophenanthridines from some thiourea derivatives

Several N-alkyl, aryl, and aralkyl-N'-2-biphenylthiourea derivatives have been synthesized and cyclodesulphurized into the corresponding 6-substituted aminophenanthridines. The ring closure was brought about with mercuric chloride, phosphoryl chloride or polyphosphoric acid. Phosphoryl chloride was found to be the most efficient in inducing ring closure and producing the highest yield of cyclized products. The results of study on the cyclodesulphurization reaction mechanism suggested the formation of a carbodiimide intermediate and identified some of the organic mercurials involved in the various stages of the reaction.     

Adduktbildung und Dimerisierung von α-Piperidinoacetonitril bei Umsetzung mit n-Butylmagnesiumchlorid. V. Mitt. über Umsetzungen von α-Aminonitrilen

Dimerisation of α-Piperidinoacetonitrile in the Reaction with n-Butylmagnesium chloride The reaction mechanisms which determine the course of the reaction between t- and n-butyl-magnesium chloride and α-piperidinoacetonitrile, have been studied. The formation of different quantities of the reaction products 3-amino-2,4-dipiperidinocrotononitrile and butyl-α-piperidinomethylketone can be explained on the basis of steric hindrace and also through the difference of nucleophilic activity of t- and n-butyl groups.     

碘普罗胺的合成

3-氨基-5-(2,3-二乙酰氧基正丙胺基甲酰基)-2,4,6-三碘苯甲酸(6)经与甲氧基乙酰氯反应、碳酸氢钠作用下水解后再经氯代得3-[(2-甲氧基)乙酰胺基]-5-(2,3-二羟基正丙胺基甲酰基)-2,4,6-三碘苯甲酰氯(4),4与N-甲基-2,3-二羟基丙胺反应制得碘普罗胺,总收率为80%(以6计)。     

Concentration determination of methyl magnesium chloride and other Grignard reagents by potentiometric titration with in-line characterization of reaction species by FTIR spectroscopy

A potentiometric titration method for methyl magnesium chloride and other Grignard reagents based on the reaction with 2-butanol in THF has been developed and validated. The method employs a commercially available platinum electrode, using an electrolyte compatible with non-aqueous solvents. Well-defined titration curves were obtained, along with excellent method precision. The endpoint was precisely determined based on the first derivative of the titration curve. Different solvents such as THF, diethyl ether and methylene chloride provided similar results with regard to sharpness of the endpoint and method precision. The method was applied to a wide array of Grignard reagents including methyl magnesium bromide, ethyl magnesium chloride, propyl magnesium chloride, vinyl magnesium chloride, phenyl magnesium chloride, and benzyl magnesium chloride with similar precision and accuracy. Application of in-line FTIR was demonstrated for in situ monitoring of the titration reaction, allowing characterization of the reaction species. An authentic spectrum of the MeMgCl-THF complex was obtained using spectral subtraction and the vibrational absorbance bands were identified. FTIR also provided an alternative for detecting the titration endpoint, and the titration results so obtained, provided a cross-validation of the accuracy of the potentiometric titration.     

Photoreactivity of LY277359 Maleate,a 5-Hydroxytryptamine3 (5-HT3) Receptor Antagonist,in Solution

Compound LY277359 maleate undergoes a photoinduced solvolysis reaction in water to generate the corresponding hydroxylated product and release chloride. Attempts to stabilize a parenteral formulation of the compound led to an investigation of possible reaction mechanisms. The data are consistent with a mechanism involving homolytic cleavage of the aryl–chloride bond followed by electron transfer to give an aryl cation intermediate. The cation thus formed reacts with surrounding nucleophiles to give the substituted product. A kinetic expression for reaction rate was derived from the mechanism, and various components of the rate constant were evaluated experimentally. The reaction is slowed with the addition of chloride, presumably via a common ion effect (enhanced retroreaction). In the absence of added chloride, the reaction can be described kinetically by an initiation term. An inner filter effect is also observed, where increasing amounts of the hydroxylated product slow the reaction. Experimental data for observed rate constants as a function of starting concentration and light intensity are fit with good correlation to an equation describing the filter effect. Additional studies evaluated the effects of various structural features of the parent compound on the rate of the reaction in glass containers. It was determined that reactivity was dependent on two features: (1) the ortho positioning of the carboxyl and ether groups, which shifted an absorption band above the container cutoff; and (2) the para orientation of the chloro group to the ether, which is para activating in the photoexcited state.     

固体光气法合成洛莫司汀

以固体光气(三光气)为起始原料，经过在无水甲苯溶液中与环己胺反应生成环己基异氰酸酯，再经与氨基乙醇和氯化亚砜的一锅法反应生成1-(2-氯乙基)—3—环己基脲(氯化物)，最后再亚硝化，即得洛莫司汀。原料易得，各步反应条件温和，操作方便，步骤比文献方法(4步)减少一步，总收率由文献方法的23．7％提高为49．8％，适于工业规模制备。