2,2-二甲基环丙烷甲酸的合成与拆分

S-( )-2,2-二甲基环丙烷甲酸是合成西司他丁(一种肾脱氢二肽酶抑制剂)的关键中间体,今设计了一条新的2,2-二甲基环丙烷甲酸合成路线并改进了拆分工艺,它是以异戊烯酸为原料,经酸的酯化、烯键的环丙烷化、酯水解制得2,2-二甲基环丙烷甲酸,收率为44．1％。其中,环丙烷化反应用锌粉／氯化亚铜-乙酰氯作为催化剂,二溴甲烷作为环丙烷化试剂,这样可以在温和的条件下进行反应,降低成本。此外用L-肉碱草酸盐作为手性拆分试剂,经酰化、成盐、部分结晶、水解得到S-( )-2,2-二甲基环丙烷甲酸．收率为16．7％,手性纯度大于95％．此路线工艺简单、环境友好、成本较低,易于工业化。     

2,2-二甲基环丙烷甲酸的合成与拆分

2,2-二甲基环丙烷甲酸是合成医药和农药的一种重要中间体,目前有多种合成方法。总结了国内外不同的合成路线,包括利用手性催化剂直接合成旋光性产物,并对合成的消旋产物拆分方法也进行了综述。     

三羟甲基乙烷在不同溶剂中溶解度的测定与关联

三羟甲基乙烷是一种重要的化工中间体,其固液相平衡数据是其分离提纯的基础。采用静态平衡法测定了288.15~318.15 K三羟甲基乙烷在甲醇、乙醇、正丙醇、异丙醇和二氧六环中的溶解度。结果表明,三羟甲基乙烷在五种溶剂中的溶解度均随温度的升高而增大,在甲醇中的溶解度最大、二氧六环中最小。采用Apelblat方程和λh方程对溶解度数据进行关联,结果表明实验中的二元体系的关联结果都较好的与实验值相吻合,为其合成及纯化工艺中溶剂的选择提供基础数据。     

催化不对称合成(S)-2,2-二甲基环丙甲酰胺

重氮乙酸乙酯和异丁烯在手性铜配合物催化下进行环丙烷化反应,以较好的产率和光学纯度得到(S)-2,2-二甲基环丙甲酸乙酯,再经过皂化、酯化、酰胺化反应制得光学纯的标题化合物.     

采用锌铜齐-二碘甲烷试剂合成2,2-二甲基环丙烷甲酸甲酯

2,2二甲基环丙烷甲酸甲酯是重要的医药中间体。以异戊烯酸为原料,经酯化、烯键的环丙烷化两步反应得到2,2-二甲基环丙烷甲酯。采用锌铜齐-二碘甲烷作环丙烷化试剂,通过单因素选优法得到最佳反应条件为：n（异戊烯酸甲酯）∶n（二碘甲烷）∶n（锌铜齐Ⅲ）=1∶3.0∶3.0;混合溶剂为V（二氯甲烷）∶V（无水乙醚）=6∶1;回流温度下反应9h。在此条件下,2,2-二甲基环丙烷甲酯的收率达到84.6%。此路线步骤简单、成本较低、收率较高。     

2-戊基蒽醌和2-乙基蒽醌在混合溶剂中溶解度测定及关联

溶解度;固液平衡;2-戊基蒽醌;2-乙基蒽醌     

芳香族羧酸溶解度的测定与关联

Solubility of benzoic acid, terephthalic acid and 2,6-naphthalene dicarboxylic acid in water, acetic acid, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulphoxide and N-methyl-2-ketopyrrolidine were measured by dynamic method. The solubilities were calculated by UNIFAC group contribution method, in which new groups, BCCOOH and NCCOOH, were introduced to express the activity coefficients of aromatic acids and new interaction parameters of the new groups were expressed as the function of temperature, which were determined from the experimental data. The new interaction parameters provided good calculated result. The experimental data were also correlated with Wilson and A-h models, and results were compared with present UNIFAC model.     

(S)-(+)-5-羟甲基-2-吡咯烷酮的合成方法改进

通过实验证明在(S)-( )-5-羟甲基-2-吡咯烷酮合成中，以硼氢化钠为还原剂时，所得产品产率和纯度都有大幅度提高；且实验操作简单方便，适合工业化。     

丙烯在仲丁醇-水溶液中溶解度的测定与关联

In order to obtain solubility data of propylene in 2-butanol water solutions, gas-liquid equilibrium(GLE) experiment was carried out at 303.15--333.15 K, 0.3-1.2 MPa with static equilibrium still. Original mass ratios of 2-butanol to water are 1:0，9:1,8:2 and 7:3, respectively. The equilibrium data are correlated with an empirical correlation. The average relative deviation (ARD) between experimental and calculated values is 2.15%,and the maximum relative deviation (MRD) is less than 5%.     

间苯二甲腈在四种溶剂中溶解度的测定及关联

采用平衡法分别测定了间苯二甲腈在甲醇、甲苯、二甲苯和苯胺四种溶剂中的溶解度,温度范围为293.15~318.15 K,并分别采用λ-h方程、Apelblat模型和Yaws模型对实验数据进行了关联。根据实验数据可以看出间苯二甲腈的溶解度在4种溶剂中均随着温度的升高而升高,并且间苯二甲腈在不同溶剂中的溶解度差别较大。通过4个体系的24个数据点的实验值与计算值相比较,三种模型的总的平均相对误差分别为5.92%、3.90%、3.86%。结果表明λ-h方程、Apelblat模型和Yaws模型都可以较好地关联间苯二甲腈在四种溶剂中的溶解度数据。     

Measurement and Correlation for Solubility of (S)-(+)-2,2-Dimethyl-cyclopropane Carbox Amide in Different Solvents

1 INTRODUCTION (S)-(+)-2,2-dimethylcyclopropane carbox amide [(+)-DMCPCA, Fig.1] is a key intermediate of Cilas- tatin, an inhibitor of dehydropeptidase-I. As the syner- gist of imipenem (an antibiotic drug), cilastatin is widely used in clinical applications and has prosper- ous prospects[1]. In industrial manufacture[2―6], as the optical intermediate, the chemical and optical purity of (+)-DMCPCA would affect the quality of cilastatin. So, the separation and purification are impo…     

Measurement and correlation for solubility of diosgenin in some mixed solvents简

The solubility data of diosgenin in mixed systems of ethanol ＋ 1-propanol （1 ： 1）, ethanol ＋ 1-butanol （1 ： 1）, ethanol ＋ isobutyl alcohol （1 ： 1）, methanol ＋ isobutyl alcohol （1 ： 1）, methanol ＋ isobutyl alcohol （1 ： 4）, ethanol ＋ 1-pentanol （1 ： 1） and carbon tetrachloride were measured over the temperature range from 289.15 K to 334.15 K by a laser monitoring observation technique at atmospheric pressure, with all mixtures mixed by volume ratio. The Apelblat equation, the ideal solution model, and the 2h equation are used to correlate the solubility data. The results show that the three models agree well with the experimental data, providing essential support for industrial design and further theoretical study.     

Determination and Correlation of Solubility for D-Xylose in Volatile Fatty Acid Solvents

The solubility of D-xylose in formic acid and binary solvents of formic acid with formic acid and acetic acid, propionic acid, n-butyric acid or isobutyric acid was measured in the temperature range from 300.35 to 325.05 K using the synthetic method by a laser monitoring technique at atmospheric pressure. The solid-liquid equilibrium data will provide essential support for industrial design and further theoretical study. The experimental data show that the solubility of D-xylose in formic acid and in the mixtures of formic acid＋acetic acid （1︰1）, formic acid＋propionic acid （1︰1）, formic acid＋n-butyric acid （1︰1）, and formic acid＋isobutyric acid （1︰1） increases with temperature. The Apelblat equation, theλh model, and the ideal solution equation correlate the solubility data well.     

辣椒碱在不同溶剂中溶解度的测定与关联

应用平衡法,以辣椒碱晶体(含辣椒碱50.4%,二氢辣椒碱37.1%,降二氢辣椒碱7.9%)为原料,在262~333 K温度下测定了辣椒碱在甲醇、乙醇、正丁醇等9种溶剂中的溶解度曲线,分别采用理想溶液模型、Apelblat模型和多项式经验方程对实验数据进行关联. 结果表明,9种溶剂中,辣椒碱的溶解度均随温度升高而增大,辣椒碱在正丁醇中的溶解度最大,在水中的溶解度最小. 计算表明,乙醚适合作为辣椒碱的冷却结晶溶剂,产率为51.23%. 模型关联结果为理想溶液模型的误差较大,多项式经验方程的误差最小.     

(S)-2-氯丙酸溶解度参数的估算与萃取剂的选择

以基团法估算出(S)-2-氯丙酸的溶解度参数为11.3,根据溶解度参数相近的原则初选出能萃取(S)-2-氯丙酸的溶剂,分别萃取(S)-2-氯丙酸;采用气相色谱法分析了各萃取剂中(S)-2-氯丙酸的质量浓度,据此求出了各萃取剂的表观分配系数,结果表明乙酸乙酯和二氯甲烷为(S)-2-氯丙酸适宜的萃取剂。     

3-(S)-巯基-1-对硝基苄氧羰基四氢吡咯的合成

为改进Carbapenem RS-533及其异构体的重要中间体3-(S)-巯基-1-对硝基苄氧羰基四氢吡咯的合成工艺,以L-羟基脯氨酸为原料,选用环己酮作催化剂,用固体硫代乙酸钾代替氢化钠和硫代乙酸,并且前两步反应不分离出中间体,经5步反应成功地合成了目标产物。关键中间体经过1HNMR检测,文中还对3-(S)-巯基-1-对硝基苄氧羰基四氢吡咯及其中间体的构型转化现象进行了分析。总收率为33.6%,适合工业化生产。     

(S)-4-(甲硫基)-2-[2-羰基-1-吡咯烷基]丁酰胺的合成

(S) 2 氨基 4 (甲硫基)丁酸甲酯盐酸盐于浓氨水中,发生酰胺化反应,制得(S) 2 氨基 4 (甲硫基)丁酰胺,收率63%;(S) 2 氨基 4 (甲硫基)丁酰胺用甲醇溶解,与浓盐酸成盐,得(S) 2 氨基 4 (甲硫基)丁酰胺盐酸盐,收率66%;(S) 2 氨基 4 (甲硫基)丁酰胺盐酸盐在相转移催化剂四丁基溴化铵(TBAB)及研细氢氧化钾的作用下,与4 氯丁酰氯发生取代、环化反应,制得(S) 4 (甲硫基) 2 [2 羰基 1 吡咯烷基]丁酰胺,收率61%。产品的结构经TLC、IR、1HNMR等进行了表征。