酰胺化

Then Doripenem came into the market in the July ,2005. We studied the synthesis of Doripemen.Firstly, we synthesized the chemical 2 from the starting material------o-hydroxylphenylacylamine through Reformastky reaction, alkylation, Diekmann reaction, enolization, esterification and etc. Secondly, we synthesized the chemical 3 from L — hydroxylproline through the protection of carboxyl, amidogen and hydroxyl group, reduction by NaBr, SN_2 substitution and Mitsumobu reaction.

我们以水杨酰胺为起始原料，经Reformatsky反应、烷基化、Diekmann环合、烯醇化、酯化等反应合成双环母核2；再从L-羟基脯氨酸出发，经酯化保护羧基、保护氨基、保护羟基、硼氢化还原酯得醇、Sn2取代和Mitsumobu反应等合成巯基侧链3；最后由化合物3经脱保护、水解得硫醇，和化合物2在二异丙基乙基胺的作用下缩合，最后Pd／C催化脱保护，历经16步反应最终得到产物多尼培南。

For the synthesis of NHC precursors, there are also several routes: condensation of glyoxal, amines and paraformaldehyde; alkylation of imidazole or monosubstituted imidazole with alkyl halide; annulation of ortho esters and 1,2-diamines; ring closure of hydrazines or amides with acetic anhydride; reduction of thiones with Na/K in THF.

关于N-杂环卡宾前体的合成途径主要有：乙二醛、伯胺和多聚甲醛的缩合反应；卤代烷与咪唑及其取代咪唑的烷基化反应；原甲酸酯与1，2-二胺的成环反应；肼或酰胺与酸酐的环化反应；用Na/K对环硫脲化合物的还原反应。

Teflubenzuron was synthesized from 2,4-difluoronitrobenzene and 2,6-dichlobenil as starting reagent through six-step reaction with the yield of 75.3%.3,5-Dichloro-2,4-difluoroaniline was synthesized by chlorination,reduction reaction from 2,4-difluoronitrobenzene,the yield was 84.5%;2,6-difluorobenzamide with the yield of 87.7% was synthesized by fluoridation and hydrolysis from 2,6-dichlobenil.

以2，4-二氟硝基苯和2，6-二氯苯腈为起始原料，经过6步反应合成伏虫隆，总收率为75.3%。以2，4-二氟硝基苯为原料，经过氯化、还原反应合成3，5-二氯-2，4-二氟苯胺，产率为84.5%；以2，6-二氯苯腈为原料，经过氟化和水解，制得2，6-二氟苯甲酰胺，产率为87.7%；将Ⅱ与二碳酸酯酰化，合成2，6-二氟苯甲酰异氰酸酯，产率为91.3%；Ⅲ与Ⅰ加成，得到杀虫剂伏虫隆，产率为95%。

Methods 4-Hydroxybenzonitrile (2) as the starting material was transformed to 4-hydroxy-thiobenzamide (3) via thioformylation. And ethyl 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylate (4), which was synthesized via cyclization from 3, was treated with hexamethylenetetramine to generate the intermediate ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate (5). The target compound febuxostat (1) was obtained from 5 by etherification, cyanidation, hydrolysis.

以羟基苯腈为原料，经硫代甲酰化得到对羟基硫代苯甲酰胺(3)，3经环合得到2-（4-羟基苯基）－4-甲基－噻唑－5-羧酸乙酯(4)，4与乌洛托品反应，得到中间体2-（3-甲酰基－4-羟基苯基）－4-甲基－噻唑－5-羧酸乙酯(5)，之后再经醚化、氰化、水解得到目标产物(1)。

A series of p-toluene sulfonylamido acetacylhydrazone derivatives were synthesized from p-toluenesulfonyl chloride which reacted with glycine to get the intermediate p-toluene sulfonylamido glycine, then through the esterification, hydrazinolysis to afford another intermediate p-toluene sulfonylamido acethydrazide, which condensed with different aldehydes to obtain the target compounds that were characterized by IR, 1H NMR, 13C NMR spectra and elemental analysis.

魏太保 ；冷艳丽；王永成；张建辉；张有明*摘要：以对甲苯磺酰氯为原料，通过与氨基乙酸反应得到中间体对甲苯磺酰氨基乙酸，再经酯化、肼解得到对甲苯磺酰氨基乙酰肼，然后与相应的醛缩合得一系列对甲苯磺酰胺基乙酰腙类化合物。其结构经元素分析， IR， 1H NMR和13C NMR确证。

In this Ph. D. dissertation, reverse microemulsion method was fully used infabricating and modifying polyacrylamide with functional and high-relative moleculeweight. The copolymerization of 2-acrylamide-2-methylpxopanesulfonic acid, fluorescent monomer 4-methoxy-N-(2-N\', N\'-dimethylamino ethyl)naphthalimide alkyl chloride quaternary ammonium salt, fluorescentmonomer 4-(N\'-methyl-1-piperazinylallyl)-N-butyl-naphthalimide chloride quaternaryammonium salt, Cationic monomer dimethylethylammonium bromide and hydrophobical monomer octadecylacrylate with acrylamide and properties of the copolymers werestudied. The interaction between five polymers and Al_2O_3(012) crystal surface have beensimulated by Materials Studio 3.0 program package, binding energies and non-bondinteraction energies and deformation energies have also been acquired.

本文以制备具有较高相对分子质量和功能型PAM为研究目的，将反相微乳液法运用到其制备及改性的有关环节，通过反相微乳液聚合工艺，将几种改性功能单体2-丙烯酰胺基-2-甲基-丙磺酸、荧光单体2-(4-甲氧基-1，8-萘二甲酰亚胺基)-乙基二甲基烯丙基氯化铵、荧光单体4-(N'-甲基-1-哌嗪基)-N-丁基-1，8-萘烯丙氯季铵盐、阳离子单体丙烯酰氧乙基-二甲基-乙基溴化铵和疏水单体丙烯酸十八酯与AM共聚，制备AMPS改性PAM、荧光示踪型PAM、阳离子单体DMB改性PAM和OA改性PAM等四类不同功能单体改性PAM，并研究其应用性能。

At 15-35℃, copolymerization of acrylamide and styene was carried out in a microemulsion system, in which AM aqueous solution was the continuous phase and St was the dispersed phase using ST-80 as surfactants, respectively. Hydroxamic functions were prepared with hydroxylamine salt at temperatures from 60℃ to 90℃.

以丙烯酰胺水溶液为连续相，苯乙烯为分散相，ST-80为乳化剂制成微乳液，在15~35℃下合成丙烯酰胺与苯乙烯的共聚物，采用程序控温方式，在60~90℃下使用硫酸羟胺将共聚物羟肟化得到产物。

Bezaldehyde was used as protective agent in first method.S-Epichloeohydrin was aminated and acidulated to give(2S)-1-Amino-3-chloro-propanol Salts.The acetylation of (2S)-1-Amino-3-chloro-propanol by acetic anhydride produced the intermediate-N-[2--3-chloropropyl]acetamide.And then at 20℃,in the presence of lithium tert-butoxide,benzyl 3-fluoro-4-morpholinophenyl carbamate react with-N-[2--3-chloropropyl]acetamide to give linezolid in total yield of 43.6%.

路线一采用苯甲醛作保护剂，使S-环氧氯丙烷氨解、酸化生成S-1-氨基-3-氯-2-丙醇盐酸盐，然后经乙酰化反应后，生成中间体-N-[2-乙酰氧基-3-氯丙基]乙酰胺，再用N-(3-氟-4-吗啉苯基)氨基甲酸苄酯和中间体在催化剂叔丁醇锂存在下25℃反应生成利奈唑酮，总产率达到43.6%。

The resultedα-methylamine was protected by acetyl chloride, and then was chlorosulfonated bychlorosulforic acid at -5℃-0℃followed by treatment with aqueous ammonia givingcompound A in 52.3% yield.

甲基胺再用乙酰基进行保护后，以HSO3Cl为试剂进行氯磺化反应，再用浓氨水进行反应，制得了乙酰基保护的苯磺酰胺类化合物。

In this research, liposoluble chlorogenic laurate was synthesized by the acylation with lauroy chloride in the existence of alkali catalyst in non-water phase, and yellowish CGL powders with a yield of 81.24% were obtained under the optimal synthesis conditions determined via single-factor tests and orthogonal experiments, that is, carrying out the acylation at 35℃ for 8h with a n:n: n ratio of 1:1:1.5 and with dimethylformamide as the solvating agent and the thinner.

文中对绿原酸进行了改性，即在碱性催化剂催化的条件下使其与月桂酰氯进行非水相的酯化反应，得到了脂溶性的绿原酸月桂酸酯。经过单因素及正交试验，确定了最佳合成条件为：以N，N-二甲基甲酰胺作为溶解、稀释剂，绿原酸／月桂酰氯／三乙胺的摩尔比为1：1：1.5，温度控制在35℃，反应时间8h。

The split between the two groups can hardly be papered over.

这两个团体间的分歧难以掩饰。

This approach not only encourages a greater number of responses, but minimizes the likelihood of stale groupthink.

这种做法不仅鼓励了更多的反应，而且减少跟风的可能性。