D(-)-α-(4-乙基-2,3-双氧代哌嗪-1-甲酰胺基)对羟基苯乙酸的合成

用双 三氯甲基碳酸酯(三光气)代替光气和4 乙基 2,3 双氧代哌嗪发生酰氯化反应,制备氧哌嗪酰氯(EOCP),进而和D(-) α 对羟基苯甘氨酸(p HPG)缩合,水解合成了D(-) α (4 乙基 2,3 双氧代哌嗪 1 甲酰胺基)对羟基苯乙酸(OH—EPCP)。酰氯化反应条件为:-15℃,n(Nu)∶n(三光气)∶n(氧哌嗪)=0 08∶0 4∶1 0,反应4h。EOCP收率大于90%。缩合反应温度15～20℃,n(EOCP)∶n(p HPG)=1 1∶1 0,反应3h。然后在室温下水解,得到白色粉末状产品。经精制后,w(OH—EPCP)>98 0%,收率(相对于p HPG用量)达88 0%。用元素分析、IR、1HNMR和MS对产品进行表征,证明了合成方法的可靠性。     

4-乙基-2,3双氧代哌嗪-1-甲酰胺基-对羟基苯乙酰氯的合成

以双三氯甲基碳酸酯(三光气,简称BTC)代替三氯氧磷与D(-)-α-(4-乙基-2,3-双氧代哌嗪-1-甲酰胺基)对羟基苯乙酸(OH-EPCP)发生酰氯化反应制备4-乙基-2,3-双氧代哌嗪-1-甲酰胺基-对羟基苯乙酰氯(OH-EPCP氯化物)。当酰氯化条件为:n(OH—EPCP)／n(BTC)=3／1,三乙胺(TEA)为引发剂,反应温度为0～5℃,反应时间2．5 h时,目标产物收率达97.6％。产品为淡黄色粉末,用高效液相色谱仪测得w(OH—EPCP氯化物)=98．14％。用红外光谱仪分析产品主要官能团(cm-1):3431,1789,1716,1682,1614、1517、1472,1188,790～860,683。1H NMR(CDCl3)分析结果(δH):11．716,7．196,6．890,5．314,4．021,3．518-3．541,3．073,1．369。     

N-乙基-2,3-双氧哌嗪紫外分光光度法建立

对用紫外分光光度法分析N-乙基-2,3-双氧哌嗪进行了探索并建立其定性定量分析方法.     

N-乙基-2,3-双氧哌嗪的工艺探索

以草酸二乙醇和N-乙基乙二胺为主要原料,经过缩合反应合成N-乙基-2,3-双氧派嗪,考察了溶剂及用量、物料配比、反应温度及时间、草酸二乙酯的滴加时间等因素对收率的影响,并通过正交实验对反应条件进行优化.在优化条件下,N-乙基-2,3-双氧派嗪的的收率可达81.52%.并在此条件下,尝试将传统的非均相反转变为均相反应,使...     

N-乙基-2,3-二氧代哌嗪的合成

以N-乙基乙二胺和草酸二乙酯为原料,在氯化胺催化作用下脱醇缩合得N-乙基-2,3-二氧代哌嗪。实验研究了反应物摩尔配比、反应时间、反应温度、催化剂用量等对N-乙基-2,3-二氧代哌嗪收率影响,得出了优惠工艺条件:催化剂用量为N-乙基乙二胺质量的1.5%,原料草酸二乙醇与N-乙基乙二胺摩尔比为1.02∶1,反应温度为20℃,乙酸用量200mL。总收率达到85%。     

1-(2-羟乙基)-4-(2-羟丙基)哌嗪基复合胺脱硫剂的合成与性能

以哌嗪(PZ)、环氧乙烷(EO)、环氧丙烷(PO)为原料,以水为溶剂,PZ先与EO反应后中间产物再与PO反应合成1-(2-羟乙基)-4-(2-羟丙基)哌嗪基复合胺脱硫剂.在PZ初始浓度为0.1 g/mL H2O,PZ:EO:PO摩尔比为1:0.8:1.2,PZ与EO、PO的反应温度分别为35℃、25℃,中间产物与PO在反应时间为150 min的优化条件下,所得复合胺脱硫剂成分为1-(2-羟乙基)-4-(2-羟丙基)哌嗪、N,N′-二(2-羟丙基)哌嗪、N-(2-羟乙基)哌嗪、N-(2-羟丙基)哌嗪、N,N′-二(2-羟乙基)哌嗪、N-(1-甲基-2-羟乙基)哌嗪和哌嗪,其对气体SO2的饱和吸收量为0.7218 mol/mol,解吸率为98.37％.     

1-(2,3-二氯苯基)哌嗪盐酸盐的合成新方法

1-(2,3-二氯苯基)哌嗪盐酸盐是重要的医药中间体。以二乙醇胺为起始原料,经氯代反应制得β,β'-二氯代二乙基胺盐酸盐,然后在水溶液中不使用催化剂条件下与2,3-二氯苯胺经环合反应合成目标化合物1-(2,3-二氯苯基)哌嗪盐酸盐。产物结构经红外光谱、核磁共振氢谱分析验证与目标化合物的结构一致。该方法经济环保,简单易操作。     

1-(3-氯苯基)-4-(3-氯丙基)哌嗪盐酸盐的合成

3-氯苯胺与双-(2-氯乙基)胺盐酸盐反应生成1-(3-氯苯基)哌嗪,再与1-溴-3-氯丙 烷反应生成1-(3-氯苯基)-4-(3-氯丙基)哌嗪,成盐得1-(3-氯苯基)-4-(3-氯丙基)哌嗪盐酸盐,总 收率45．7％。     

芬斯匹利的合成研究

以1-苯乙基-4-哌啶酮为原料,与碘化三甲氧硫金翁反应得到环氧化合物,再用氨气开环得到氨基醇,最后与三聚光气反应得到目标化合物——芬斯匹利。产品总收率为32%。     

2-甲基-4-三氟甲基噻唑-5-甲酰氯的制备

以固体光气为氯化试剂,二氯乙烷为反应溶剂,2-甲基-4-三氟甲基噻唑-5-甲酸与固体光气发生氯化反应,得到2-甲基-4-三氟甲基噻唑-5-甲酰氯。反应中通过调节滴加固体光气二氯乙烷溶液的时间,来控制反应速度,使固体光气得到充分利用;通过热回流的方式,热解离固体光气,避免了解聚剂的引入;以蒸馏的方式回收了反应溶剂,实现了溶剂套用5次以上,收率大于99%,产品含量大于99%,副产盐酸,三废量少,已完成中试。     

哌拉西林钠的合成工艺改进

以双氧哌嗪为原料,经酰氯化制得双氧哌嗪酰氯液,它与氨苄青霉素三水酸在溶媒中缩合得哌拉西林酸,哌拉西林酸与醋酸钠成盐制得哌拉西林钠。该方法具有合成路线简单、成本低、产品纯度高、对操作条件要求较宽等特点。     

2,3-二氯喹喔啉-6-羧酰氯的制备

3,4-二氨基苯甲酸与草酸二乙酯原料,合成了2,3-二羟基喹喔啉-6-羧酸,收率90.4%。继而以三光气为氯化剂,反应制备了2,3-二氯喹喔啉-6-羧酰氯,最佳的工艺条件为:1.5g2,3-二羟基-6-羧酸喹喔啉,15mL三氯乙烯,0.6mL二甲基甲酰胺均匀混合回流,以10mL三氯乙烯溶解4.5g三光气,2h内滴加完,继续回流4h,得2,3-二氯喹喔啉-6-羧酰氯,收率达到80.1%。     

Non-Chlorine Bleaching of Kraft Pulp II. Ozonation of Methyl 4-O-Ethyl-β-D-glucopyranoside (1) Preparation of Authentic Carbonyl Sugars and Their Analysis by Gas Chromatography and Mass Spectrometry

Methyl 4-O-ethyl-β-D-glucopyranoside (1) was prepared as a model compound for cellulose to investigate the reactions of ozone with polysaccharides during ozone bleaching of kraft pulp. The model compound was converted into authentic carbonyl sugars, methyl 3,6-di-O-acetyl-4-O-ethyl-β-D-arabino-hexopyranosidulose (2), methyl 2,6-di-O-acetyl-4-O-ethyl-β-D-ribo-hexopyranoside-3-ulose (3), methyl 2,3-di-O-acetyl-4-O-ethyl-β-D-gluco-hexodialdo-1,5-pyranoside (4). These carbonyl sugars were converted into O-methyloximes and analyzed by gas chromatography and mass spectrometry.     

Scaling up microreactors for kilogram-scale synthesis of piperacillin: Experiments and computational fluid dynamics simulations

In this study, two membrane dispersion microreactors in series are used to synthesize piperacillin with low impurity content in kilogram scale. By combining experiments and computational fluid dynamics simulations, the membrane size and cross-sectional area are scaled up from 2 mm × 0.7 mm and 2 mm × 1 mm to 6.5 mm × 2.5 mm and 6.5 mm × 3.5 mm, respectively, and the reaction time is extended from ~10 to ~60 min, which achieves that the synthesis scale of each batch is increased from 15 g to 1 kg. Subsequently, the effects of distance between ammonia feed and 4-ethyl-2,3-dioxo-1-piperazine carbonyl chloride feed, pH, circulation flow rate, and dispersed phase flow rate on solution concentration are discussed. The final piperacillin product with an average yield of ~94.70%, a purity exceeding 99.7%, the impurity D content ~0.077% and E content ~0.045%, satisfies the requirements of pharmacopeia regarding antibiotic impurities.     

环酰菌胺的合成

以(2,3-二氯-4-羟基苯基)偶氮苯为原料,制备了2,3-二氯-4-羟基苯胺,收率为90%;然后与1-甲基环己基甲酰氯反应制备标题化合物环酰菌胺,此步反应收率达92.4%.两步反应总收率为83.2%.     

A Mild Procedure for the Preparation of Phenols from Polycyclic Aromatic Ketones

A mild method is described for the preparation of phenols from polycyclic aromatic ketones. Ketones which have the carbonyl group adjacent to an aromatic ring can be converted to phenyl selenides by treatment with phenylselenenyl chloride in ethyl acetate at room temperature. Oxidation with 30% hydrogen peroxide in tetrahydrofuran at room temperature affords the corresponding phenols in generally high yield. Phenolic derivatives of phenanthrene, fluoranthene, benz[a]anthracene, and benzo[a]pyrene were prepared using this general procedure. Oxidation of the 2-phenylselenenyl derivative of 1,12c-dihydrobenzo[j]fluoranthene with 30% hydrogen peroxide resulted in anomalous formation of the 2,3-quinone instead of 3-hydroxybenzo[j]fluoranthene. The mildness and selectivity of the selenation-oxidation procedure was demonstrated by the aromatization of a cyclic ketone without concomitant dehydrogenation in a partially saturated ring. β-Tetralone reacted with phenylselenenyl chloride at room temperature to form a single compound in high yield identified as 2-naphthol. This reaction occurred in the absence of an added oxidizing agent. Another β-tetralone-type ketone, 1,2-dihydrophenanthren-3(4H)-one, was converted into 3-hydroxyphenanthrene under the same reaction conditions. Similar treatment of 1,10b-dihydrofluoranthen-2(3H)-one failed to yield either 2-hydroxyfluoranthene or the 2,3-quinone.     

含哌啶基的酒石酸衍生物的合成

酒石酸衍生物在对映体拆分和不对称合成中得到广泛应用。文章以酒石酸二乙酯为原料,经过与苯甲醛缩合,氯化铝锂还原,对甲苯磺酰氯酰化,与哌啶亲核取代反应和脱保护五步反应得到1,4-二哌啶基-2,3-丁二醇。该化合物与氢化铝锂络合用于制备手性还原剂。     

2,3-戊二酮的合成

乙醛和丙醛经3-乙基-4-甲基-5-(2-羟乙基)-1,3-噻唑溴盐催化交叉偶联反应生成以C5偶姻为主的偶姻混合物,偶姻混合物再经H2O2间接氧化、分离制备了2,3-戊二酮。优化的偶联反应条件是:m(乙醛)∶m(丙醛)∶m(催化剂)∶m(Na2CO3)=110∶90∶2∶1;反应温度125℃;压力为1MPa。乙醛和丙醛转化率分别达到94%和95%,C5偶姻产率为48.8%,偶姻总产率为90%。混合偶姻在浓H2SO4存在下,用质量分数30%H2O2/FeSO4.7H2O氧化,m(FeSO4.7H2O)∶m(浓H2SO4)∶m(H2O)∶m(偶姻)∶m(H2O2)=11∶2∶4∶2∶3,2,3-戊二酮相对于偶姻的总产率为44%,邻二酮总产率为84%。经常压分馏,可以分别得到质量分数≥98%的2,3-戊二酮、丁二酮和3,4-己二酮产品。铁离子氧化剂重复使用,邻二酮化合物收率没有明显下降。     

4-乙氧基-2,3-二氟苯乙酮的合成与表征

以2,3-二氟苯乙醚和乙酰氯为起始原料,经傅克反应合成了质量分数99%以上的液晶中间体4-乙氧基-2,3-二氟苯乙酮,对目标化合物进行了1HNMR、IR和GC-MS表征。以二氯甲烷为反应溶剂,当n(2,3-二氟苯乙醚)∶n(三氯化铝)∶n(乙酰氯)=1∶1.14∶1.3,反应温度为-10～-5℃,反应时间为1 h时,反应效果最佳,产物质量分数为89.2%,2,3-二氟苯乙醚质量分数为4.83%,副产物4-乙酰基-2,3-二氟苯酚醋酸酯质量分数为0.12%,产物异构体未检出。根据实验结果对傅克反应副产物产生的原因进行了推测。