2-乙氧羰基-3-溴-4-甲基-5-甲酰基吡咯的制备

以2-乙氧羰基-3-溴-4,5-二甲基吡咯为原料,合成了托尼卟吩A的重要中间体2-乙氧羰基-3-溴-4-甲基-5-甲酰基吡咯,考察了不同氧化剂、温度及时间对产物收率的影响。结果表明,当以硝酸铈铵为氧化剂,且它与反应物的摩尔比为4.2∶1,反应温度为0℃,反应时间为1.5 h时,产物的收率达到最高值94.2%。     

2-氨基-4-氯-5-硝基苯酚的生产工艺

以2-氨基-4-氯苯酚为原料。经乙酰化、闭环、硝化、碱解和酸化合成2-氨基-4-氯-5-硝基苯酚,精制品总收率为64％。     

2-甲基-2-羟基-1-苯基-1-丁酮的合成

首先由2-甲基丁酸、氯化亚砜,合成了2-甲基丁酰氯,其次,以无水三氯化铝为催化剂,苯与2-甲基丁酰氯反应合成了2-甲基-1-苯基-1-丁酮,当催化剂用量为22 g,2-甲基丁酰氯的滴加时间为1.5 h,苯与2-甲基丁酰氯物质量的比为5.0∶1时,收率为92.6%。最后在氢氧化钠水溶液中,以四氯化碳为氯化试剂,四丁基溴化铵为相转移催化剂,将2-甲基-1-苯基-1-丁酮直接氯代和水解制得2-甲基-2-羟基-1-苯基-1-丁酮。当四氯化碳的用量为12 mL,四丁基溴化铵用量为6 g,氢氧化钠浓度为17%,反应时间为6 h时,产品的收率可达90.3%。通过元素分析、红外光谱分析、质谱对产品进行了结构表征。     

6-氟-4-氧代-3,4-二氢-2H-1-苯并吡喃-2-甲酸的合成

以对氟苯酚为原料,经酚羟基甲基化、与顺丁烯二酸酐发生傅-克酰基化反应、在碱性条件下迈克尔加成环合,合成6-氟-4-氧代-3,4-二氢-2H-1-苯并吡喃-2-甲酸.研究了环合反应条件,得到了最佳反应条件:以10%NaHCO3为催化剂,回流温度下,反应时间15min环合为最佳.总产率78%.     

6-甲基-4-苯基-5-乙氧羰基-3,4-二氢嘧啶-2-硫酮的合成

利用Biginelli缩合反应,以苯甲醛、乙酰乙酸乙酯和硫脲为原料,合成了6-甲基-4-苯基-5-乙氧羰基-3,4-二氢嘧啶-2-硫酮。采用单因素法考察了催化剂种类、乙酰乙酸乙酯的用量、催化剂用量、反应时间、溶剂种类等对反应产率的影响。最佳反应条件为:以0.10g氨基磺酸作催化剂,以10mL无水乙醇为溶剂,以10mmol苯甲醛、24mmol乙酰乙酸乙酯和15mmol硫脲为原料,在搅拌回流条件下反应3h。产率为79.0%。     

2-甲基-5-取代苯硫基-1,3,4-噻二唑的合成研究

以取代碘苯和2-巯基-5-甲基-1,3,4-噻二唑为原料,合成了一系列2-甲基-5-取代苯硫基-1,3,4-噻二唑类化合物,确定最佳合成条件为:以碘化亚铜作催化剂、2-吡啶甲酸作配体,于70～80℃在二甲基亚砜中反应24～36h。目标化合物结构经核磁共振氢谱、核磁共振碳谱、红外光谱、质谱分析确证。     

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。     

3-溴-5-叔丁基-2-羟基苯甲醛的合成研究

以冰乙酸为溶剂,以5-叔丁基-2-羟基苯甲醛和溴素为原料,合成了3-溴-5-叔丁基-2-羟基苯甲醛。考察了溶剂、反应温度、物料比、反应时间等对3-溴-5-叔丁基-2-羟基苯甲醛收率的影响,合成的优化工艺条件为:n(5-叔丁基-2-羟基苯甲醛)∶n(溴素)=1∶1.1,反应温度60℃,反应时间10 h,在此工艺下,收率可达到88.2%,产品经MS、1H NMR确认。     

4-(吡啶-2-甲氧基)-5,6,7,8-四氢萘酚-1-胺的合成

以α-萘酚为起始原料,经过5步反应得到4-(吡啶-2-甲氧基)-5,6,7,8-四氢萘酚-1-胺,总收率为27%。该制备工艺原料易得、反应条件温和、后处理简单,适合实验室的小规模制备。     

2-（3-氯-2-吡啶基）-5-氧代-3-吡唑烷甲酸乙酯的合成

以3-氨基吡啶为原料,经取代、重氮化得到2,3-二氯吡啶,再与水合肼经亲电取代制得3-氯-2-肼基吡啶。所得产品无需提纯可直接用于下一步反应。所得产物与马来酸二乙酯在氮气保护条件下,以无水乙醇为溶剂,反应得到有机中间体2-(3-氯-2-吡啶基)-5-氧代-3-吡唑烷甲酸乙酯,反应总产率为48.0%。所得产物经IR、1HNMR确定其结构。并对合成工艺进行优化,所得适宜工艺条件(以3-氯-2-肼基吡啶228.57 mmol计):在无水无氧反应体系中,回流状态下滴加马来酸二乙酯速度为10 s/滴时,回流反应1 h,产率为80.1%。     

脂肪酶催化合成环十五内脂的酸碱效应

以15-羟基十五烷酸甲酯为底物,进行了脂肪酶催化合成环十五内酯研究,考察了酶活性与pH值的关系,探讨了酶粉pH值记忆和有机相酸碱性对内酯化反应的影响。结果表明,pH=6~7时脂肪酶的水解活力最高,pH=6~6.5时15-羟基十五烷酸甲酯转化环十五内酯的转化率最高,添加有机酸碱对内酯化反应产生不利影响。     

溴虫腈的合成

以对氯苯甘氨酸、三氟乙酸、2-氯丙烯腈为原料，经内酯化、吡咯环化、溴代和乙氧甲基化4步反应合成溴虫腈，总收率大于73．4％，纯度大于99％，均高于国内同行水平4％～5％。该路线采用价格低廉的三氟乙酸和二乙氧基甲烷代替昂贵的三氟乙酸酐和二溴甲烷，大大降低了原料成本，避免了强致癌物的使用，条件温和，对工艺要求不高，所有原料在国内皆有生产，来源丰富，适宜于工业化生产。     

Heterogeneous liquid-phase lactonization of 1,4-butanediol using H3+xPMo12−xVxO40 (x=0–3) catalysts immobilized on polyaniline

In order for successful application of heteropolyacids (HPAs) as heterogeneous catalysts to liquid-phase lactonization of 1,4-butanediol, H_3+xPMo_12−xV_xO₄₀ (x=0–3) HPAs were immobilized on polyaniline (PANI) by one-step and two-step methods. Aniline was polymerized in the presence of HPA in the one-step preparation method, while HPA was immobilized on the ready-made PANI support in the two-step method. It was found that HPAs were molecularly dispersed and strongly immobilized in/on the PANI support as charge-compensating components. Most HPAs in the two-step HPA---PANI catalysts were immobilized only on the surface of PANI support. The surface areas of the two-step HPA---PANI catalysts were much higher than those of the one-step catalysts, which is important from the practical point of applications. Thermal stability of PANI support was much enhanced by the binding with HPA, and thermal stability of the two-step HPA---PANI catalysts was superior to the one-step catalysts. In the lactonization of 1,4-butanediol, catalytic activities were in the following order: two-step HPA---PANI>one-step HPA---PANI>unsupported HPA; H₆PMo₉V₃O₄₀---PANI>H₅PMo₁₀V₂O₄₀---PANI>H₄PMo₁₁V₁O₄₀---PANI>H₃PMo₁₂O₄₀---PANI. High activity of V-containing two-step catalysts and easiness of catalyst recovery in the liquid-phase reaction make them good candidates for an energy-saving lactonization process of 1,4-butanediol.     

肉桂酰香豆素-7-酚酯的合成及其荧光性能

以2,4-二羟基苯甲醛为起始原料经过Knoevehgel反应、内酯化反应和酰化反应合成肉桂酰香豆素-7-酚酯。使用HNMR、红外、紫外可见光谱对所合成的催化剂进行表征,并对所合成的化合物进行荧光测试,测试结果表明所合成化合物荧光的λ_（max）位于406 nm。     

Trimethyl Lock: A Multifunctional Molecular Tool for Drug Delivery,Cellular Imaging,and Stimuli‐Responsive Materials

Trimethyl lock (TML) systems are based on ortho‐hydroxydihydrocinnamic acid derivatives displaying increased lactonization reactivity owing to unfavorable steric interactions of three pendant methyl groups, and this leads to the formation of hydrocoumarins. Protection of the phenolic hydroxy function or masking of the reactivity as benzoquinone derivatives prevents lactonization and provides a trigger for controlled release of molecules attached to the carboxylic acid function through amides, esters, or thioesters. Their easy synthesis and possible chemical adaption to several different triggers make TML a highly versatile module for the development of drug‐delivery systems, prodrug approaches, cell‐imaging tools, molecular tools for supramolecular chemistry, as well as smart stimuliresponsive materials.     

(S)-(+)-γ-苄氧基甲基-γ-丁内酯的合成研究

以Ｌ 谷氨酸为原料,首先在－５～０℃条件下重氮化,随后常温内酯化,然后在对甲苯磺酸催化下于苯中回流进行酯化,用硼氢化钠在常温下还原,最后用氧化银作为碱发生常温威廉逊（Ｗｉｌｉａｍｓｏｎ）醚化反应,以３２３％的总产率合成了标题化合物。     

抗癌药盐酸吉西他滨的合成工艺研究

S-甘油醛缩丙酮经Reformasty反应、脱异丙叉基保护、内酯化及双苯甲酰化得到2-脱氧-2,2-二氟-D-赤型-呋喃戊糖-1-酮-3,5-二苯甲酸酯,再经四氢铝锂还原、甲磺酰化、缩合得2-脱氧-2＇,2＇-二氟胞苷-3＇,5＇-二苯甲酸酯,然后经脱保护基,成盐后经丙酮-水体系重结晶分离得盐酸吉西他滨,总收率6.2%。     

Characterization of acidic groups in oxycelluloses III. Effect of cation freeing and blocking on estimation of carboxyl groups and lactones by the idometric method

A differentiation between free carboxyl and various lactone groups in different types of oxycelluloses was carried out based on the variation in their reaction rate with KI/KIO₃ solution. For oxycelluloses prepared under acidic conditions, a large proportion of carboxyl groups are present in free form. Each oxycellulose was also studied after cation freeing as well as after blocking the free carboxyl groups by treatment with sodium chloride. Cation freeing was found to cause considerable lactonization of carboxyl groups; sodium chloride treatment blocked them only partially.     

Chemoenzymatic Synthesis of Fragrance Compounds from Stearic Acid

Fatty acids are versatile precursors for fuels, fine chemicals, polymers, perfumes, etc. The properties and applications of fatty acid derivatives depend on chain length and on functional groups and their positions. To tailor fatty acids for desired properties, an engineered P450 monooxygenase has been employed here for enhanced selective hydroxylation of fatty acids. After oxidation of the hydroxy groups to the corresponding ketones, Baeyer–Villiger oxidation could be applied to introduce an oxygen atom into the hydrocarbon chains to form esters, which were finally hydrolyzed to afford either hydroxylated fatty acids or dicarboxylic fatty acids. Using this strategy, we have demonstrated that the high-value-added flavors exaltolide and silvanone supra can be synthesized from stearic acid through a hydroxylation/carbonylation/esterification/hydrolysis/lactonization reaction sequence with isolated yields of about 36 % (for ω−1 hydroxylated stearic acid; 100, 60, 80, 75 % yields for the individual reactions, respectively) or 24 % (for ω−2 hydroxylated stearic acid). Ultimately, we obtained 7.91 mg of exaltolide and 13.71 mg of silvanone supra from 284.48 mg stearic acid.     

Influence of method of preparation of Co-Cu/MgO catalyst on dehydrogenation/dehydration reaction pathway of 1, 4-butanediol

Co-Cu/MgO catalyst was prepared by two different methods; one involving generation of Cu and Mg mixed carbonate by coprecipitation followed by mixing it with Co carbonate (Catalyst-1) and the second method involving coprecipitation of all the nitrate salts to get the mixed carbonate (Catalyst-2). Contacting 1,4-butanediol on Catalyst-1 under vapor phase yielded γ-butyrolactone via dehydrogenation, whereas, Catalyst-2 yielded tetrahydrofuran via dehydration. Higher Cu dispersion obtained by N₂O pulse chemisorption due to smaller particle size in Catalyst-1 is found to be responsible for the lactonization activity. The presence of strong acid sites, as determined by NH₃ TPD, in Catalyst-2 leads to tetrahydrofuran formation by dehydration of 1,4-butanediol.