Synthesis of Diethyl Oxalate by a Coupling
脂肪族碳二亚胺衍生物的合成【毕业作品】
BIYESHEJI （20 届）脂肪族碳二亚胺衍生物的合成摘要碳二亚胺（Carbodiimide）具有累积双键（-N=C=N-）结构，这类化合物常用做化学反应中的脱水剂，反应条件温和简便，具有很大的应用前景。
本文通过探索，主要介绍了脂肪族脲（对正丁基脲、对异丁基脲、对仲丁基脲等）在脱水剂对甲苯磺酰氯，催化剂三乙胺，溶剂石油醚中，经过加热回流反应脱水，制备碳二亚胺的方法。
该方法反应条件温和方便，后处理简单，产品收率高，适合于大量生产。
关键词：碳二亚胺，脱水剂，脲脱水，对甲苯磺酰氯，三乙胺，高收率，累积双键AbstractCarbodiimide has accumulated a double bond (N = C = N -) structure, These compounds are commonly used as the dehydrating agent in chemical reactions. It requires that the moderate convenient condensation conditions, has great application prospect. In this article, through exploring, mainly introduced the aliphatic urea (double n-butyl urea, double isobutyl urea, Double 2 - methyl propyl urea ) in the dehydrating agent p-toluene sulfonyl chloride, triethylamine catalyst, aprotic solvent, under the existence of petroleum ether through heating reflux dehydration reaction, preparation method of Carbodiimide. The method is mild reaction conditions and convenient, simple post-processing, product yield is high, suitable for mass production.Key Words：Carbodiimide, dehydrant, Urea dehydration, p-toluene sulfonyl chloride, triethylamine, High yield, cumulative double bond目录摘要 (I)Abstract (II)第一章前言 (1)1.1碳二亚胺简介 (1)1.1.1结构与稳定性 (1)1.1.2歧化作用 (1)1.1.3光谱性质 (1)1.2碳二亚胺的反应 (2)1.2.1加成反应 (2)1.2.2环化反应 (2)1.2.3 缩合反应 (2)1.3碳二亚胺的应用 (3)1.3.1碳二亚胺在多肽合成中的应用 (3)1.3.2碳二亚胺在有机合成中的应用 (3)1.3.3. 碳二亚胺在高分子方面的应用 (3)1.3.4. 碳二亚胺在工业方面的应用 (4)1.4碳二亚胺的合成 (4)1.4.1硫脲衍生物合成碳二亚胺 (4)1.4.2异氰酸酯合成碳二亚胺 (5)1.4.3脲合成碳二亚胺 (6)第二章实验部分 (8)2.1实验仪器与试剂 (8)2.2合成路线 (8)2.3对叔丁基碳二亚胺的合成 (8)2.3.1对甲苯磺酰氯-碳酸钾法 (8)2.3.2 对甲苯磺酰氯-三乙胺法 (9)2.4对异丁基碳二亚胺的合成 (10)2.4.1对甲苯磺酰氯-碳酸钾法 (10)2.4.2对甲苯磺酰氯-三乙胺法 (10)2.5对正丁基碳二亚胺的合成 (12)2.6对仲丁基碳二亚胺的合成 (13)第三章结果与讨论 (16)3.1碳二亚胺的合成方法 (16)3.1.1 对甲苯磺酰氯-碳酸钾法 (16)3.1.2 对甲苯磺酰氯-三乙胺法 (17)3.2产品中主要杂质分析 (17)3.3产品纯化 (18)3.4产品性状分析 (18)第四章结论与展望 (19)参考文献 (20)致谢 (21)第一章前言碳二亚胺（Carbodiimide）具有累积双键（-N=C=N-）结构，这类化合物常用做化学反应中的脱水剂，主要用于活化羧基，促使酰胺和酯的生成等。
腈吡螨酯(cyenopyrafen)的合成与杀螨活性
2019年6月◆创制与生测◆_______________________________________收稿日期:2018-10-08基金项目:“十三·五”国家重点研发计划项目（2016YFD 0300708）作者简介:程岩（1982—），硕士。
研究方向：新农药创制。
E -mail ：chengyan02@ 通讯作者:李斌（1964—），教授级高工，主要从事新农药创制研究。
E-mail ：libin1@腈吡螨酯（cyenopyrafen ）的合成与杀螨活性程岩,吴鸿飞,罗艳梅,李斌*（沈阳中化农药化工研发有限公司，新农药创制与开发国家重点实验室，沈阳110021）摘要:腈吡螨酯是由日产化学公司开发的丙烯腈类杀螨剂。
以丙酮、草酸二乙酯和对叔丁基苯乙腈等为起始原料经7步反应合成了腈吡螨酯,目标化合物的结构经1H NMR 确证。
初步生物活性测试结果表明,腈吡螨酯对朱砂叶螨具有优异的活性。
关键词:腈吡螨酯;杀螨剂;合成;杀螨活性中图分类号:TQ 454.2文献标志码:Adoi :10.3969/j.issn.1671-5284.2019.03.003Synthesis of Cyenopyrafen and Its Acaricidal ActivityCheng Yan,Wu Hong-fei,Luo Yan-mei,Li Bin *(State Key Laboratory of the Discovery and Development of Novel Pesticide,Shenyang Sinochem Agrochemicals Research and Development Co.,Ltd.,Shenyang 110021,China )Abstract:Cyenopyrafen is a kind of new acrylonitrile acaricides,which is commercialised in 2009by Nissan Chemicals.Cyenopyrafen was synthesized from acetone,diethyl oxalate and 4-tert -butylphenylacetonitrile via seven steps.The structure of the target compound was confirmed by 1H NMR.The results of preliminary biological activity test showed that cyenopyrafen had excellent activities against Tetranychus cinnabarinus .Key words:cyenopyrafen;acaricide;synthesis;acaricidal activity 螨类，尤其是以植食性为主的农业螨类，在世界各地的农作物上都有发现。
(完整word版)药物合成反应(闻韧_第三版)课后翻译(word文档良心出品)
1、About 216–224 g. (1.62–1.68 moles) of powdered anhydrous aluminum chloride is added to a 1Lthree-necked flask.在1L的三口烧瓶中加入大约216-224g(1.62–1.68 moles)的无水三氯化铝。
While the free-flowing catalyst is stirred (Note 3), 81 g. (0.67 mole) of acetophenone is added from the dropping funnel in a slow stream over a period of 20–30 minutes. 自由流动的催化剂边搅拌边用滴液漏斗缓慢滴加81g苯乙酰。
Considerable heat is evolved, and, if the drops of ketone are not dispersed, darkening or charring occurs. 放热反应，假如滴加的酮不能被分散，就会变黑或是碳化。
When about one-third of the acetophenone has been added, the mixture becomes a viscous ball-like mass that is difficult to stir.当三分之一的乙酰苯被滴加，反应混合物变成一个很难搅拌的粘性的球状团块。
Turning of the stirrer by hand or more rapid addition of ketone is necessary at this point. 在这时，改用手动搅拌或快速滴加酮是非常必要的。
The addition of ketone, however, should not be so rapid as to produce a temperature above 180°. 然而，速度不能太快，当反应温度超过180℃时。
咔唑9位取代反应
Organic Syntheses, Coll. Vol. 10, p.396 (2004); Vol. 77, p.153 (2000).9-ETHYL-3,6-DIMETHYLCARBAZOLE (DMECZ)[ 9H-Carbazole, 9-ethyl-3,6-dimethyl- ]Submitted by Jason R. Buck, Minnie Park, Zhiwei Wang, Daniel R. Prudhomme, and Carmelo J.Rizzo1 .Checked by Gilles Chambournier and David J. Hart.1. ProcedureA.3,6-Dibromo-9-ethylcarbazole. In an oven dried, 1-L, round-bottomed flask equipped with a magnetic stir bar and a rubber septum are placed 3,6-dibromocarbazole (10.0 g, 31.0 mmol) (Note 1) and sodium hydroxide pellets (1.2 g, 30.0 mmol) in 500 mL of dry acetone(Note 2) under an argon atmosphere. Diethyl sulfate (4.1 mL, 31.0 mmol) (Note 3) is added dropwise over 15 min to the stirred reaction mixture at room temperature. After the addition, the reaction is stirred for 8 hr at which time all solids are removed by filtration and the solvent is removed under reduced pressure to give a yellow solid. The residue is dissolved in ethyl acetate (200 mL) and successively washed with aqueous saturated sodium bicarbonate (3 × 75 mL), brine (3 × 75 mL) and water (3 × 75 mL). The organic layer is dried over sodium sulfate , filtered and the solvent removed under reduced pressure to give a pale yellow solid. Recrystallization from 95% ethanol (ca. 350 mL) gives 3,6-dibromo-9-ethylcarbazole (8.85 g, 81% yield) as white needles, mp 139-141°C (lit.2 mp 137-138°C) (Note 4). The filtrate is evaporated and the resulting solid recrystallized to give additional product (0.24 g, 2% yield).B.9-Ethyl-3,6-dimethylcarbazole. In an oven-dried, 1-L, three-necked, round-bottomed flask equipped with a magnetic stir bar, a reflux condenser and a rubber septum are placed 3,6-dibromo-9-ethylcarbazole (7.1 g, 20.0 mmol) and [1,3-bis(diphenylphosphino)propane]nickel(II) chloride (0.54 g, 1.0 mmol) (Note 5) in 500 mL of dry ether(Note 6) under an argon atmosphere (Note 7). To the stirred solution at room temperature is added methylmagnesium bromide (30 mL, 60.0 mmol) (Note 8) dropwise over 20 min via an addition funnel. During the addition, the color of the solution turns from orange to yellow to brown. After the addition, the reaction mixture is heated at reflux for 2 hr at which time the reaction is judged complete by TLC analysis. The reaction mixture is cooled to room temperature, then carefully quenched with aqueous saturated ammonium chloride (25 mL) at which point a brown precipitate forms. All the contents of the reaction are transferred to a separatory funnel and successively washed with aqueous saturated sodium bicarbonate (3 × 50 mL), brine (3 × 50 mL) and deionized water (3 × 50 mL). The combined aqueous layers are extracted with ethyl acetate (3 × 50 mL). The combined organic extracts are dried over sodium sulfate, filtered and the solvent is removed under reduced pressure to give a yellow solid. Recrystallization from ethanol gives 9-ethyl-3,6-dimethylcarbazole (3.62 g, 81% yield) as white needles, mp 57-58°C (lit.2 mp 62-63°C) (Note 9). The filtrate is evaporated and the resulting solid recrystallized from ethanol to give additional product (0.39 g, 9% yield).2. Notes1. 3,6-Dibromocarbazole (99%) was obtained from Aldrich Chemical Company, Inc. , and was recrystallized from ethanol before use.2. ACS grade acetone was dried over activated four angstrom molecular sieves.3. Diethyl sulfate (H IGHLY TOXIC ; CANCER SUSPECT AGENT ) was obtained from Aldrich Chemical Company, Inc. , and used as received.4. The spectra are as follows: 1H NMR (CDCl 3) δ: 1.39 (t, 3 H, J = 7.2), 4.29 (q, 2 H, J = 7.2), 7.26 (d, 2 H, J = 8.7), 7.55 (dd, 2 H, J = 8.7, 1.9), 8.12 (d, 2 H, J = 1.9) ; 13C NMR (CDCl 3) δ: 13.7 (CH 3), 37.8 (CH 2), 110.1 (CH), 111.9 (C), 123.3 (CH), 123.5 (C), 129.0 (CH), 138.8 (C) ; MS (EI): m/e (relative intensity) 355 (48), 353 (100), 351 (52), 340 (48), 338 (92), 336 (46) . Anal. Calcd for C 14H 11Br 2N: C, 47.84; H, 3.16. Found: C, 47.63; H, 3.13.5. [1,3-Bis(diphenylphosphino)propane]nickel(II) chloride (99%) was purchased from Strem Chemical and used as received.6. Diethyl ether was freshly distilled from a sodium /benzophenone ketyl.7. Gentle warming with a heat gun may be required to dissolve completely 3,6-dibromo-9-ethylcarbazole in ether .8. Methylmagnesium bromide was purchased from Aldrich Chemical Company, Inc. as a 3.0 M solution in diethyl ether and used as received.9. The spectra are as follows: 1H NMR (CDCl 3) δ: 1.14 (t, 3 H, J = 7.2), 2.58 (s, 6 H), 4.34 (q, 2 H, J = 7.2), 7.31 (s, 4 H), 7.91 (s, 2 H) ; 13C NMR (CDCl 3) δ: 13.7 (CH 3), 21.3 (CH 3), 37.5 (CH 2), 108.0 (CH), 120.3 (CH), 122.8 (C), 126.7 (CH), 127.6 (C), 138.4 (C) ; MS (EI): m/e (relative intensity) 223 (69), 208 (100) . Anal. Calcd for C 16H 17N: C, 86.05; H, 7.68. Found: C, 85.35; H, 7.70.Waste Disposal InformationAll toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.3. DiscussionSince its introduction by Barton and McCombie, the deoxygenation of thionocarbonyl derivatives of alcohols has become an important synthetic reaction and a valuable method for the generation of carbon-centered radicals.3,4 5 Xanthates, thionobenzotes, thionocarbonyl imidazolides, aryloxy thionocarbonate, N-phenylthionocarbamates and oxalate esters are conveniently deoxygenated with tin or silicon hydrides in boiling benzene or toluene .4,5,6 7 8 9 10 11Saito demonstrated that benzoates and m-(trifluoromethyl)benzoates of secondary alcohols could be deoxygenated via a photoinduced electron-transfer (PET) mechanism using 9-methylcarbazole (MCZ) as the electron donor.12,13 14 The mechanism involves an excited state electron-transfer from MCZ to the benzoate to give the MCZ/benzoate radical ion pair; solvent cage escape is promoted by salts such as magnesium perchlorate . Protonation of the benzoate radical anion gives radical 1, which undergoes β-scission to the deoxygenation radical. Hydrogen atom transfer from the solvent (i.e., 2-propanol ) gives the deoxygenated product. Oxidation of the solvent radical by MCZ radical cation regenerates the donor. In principle, the donor could be used in substoichiometric amounts since it is regenerated; however, in practice one full equivalent of MCZ is necessary for the PET deoxygenation.The submitters reasoned that the radical cation of MCZ was undergoing side reactions or degradation faster than the steps leading to the regeneration of MCZ. The radical cations of carbazoleshave been previously studied by cyclic voltammetry (CV) and it was found that MCZ was irreversibly oxidized, indicating that the radical cation undergoes side reactions faster than the CV time scale.2 15 The electrochemical oxidation of some 9-alkyl carbazoles substituted at the 3- and 6-positions showed improved reversibility, indicating that the radical cations were longer-lived. The submitters demonstrated that 10-20 mol % of 9-ethyl-3,6-dimethylcarbazole (DMECZ) could efficiently deoxygenate benzoate and m-(trifluoromethyl)benzoates in high yields (Table).16 The increased lifetime of the radical cation of DMECZ allows for the donor to be regenerated and thus it can be used in substoichiometric amounts. Importantly, it appears that DMECZ is a more reactive donor. Because of the toxicity of tin species, there has been interest in developing alternative methods for the Barton and related deoxygenation reactions and some success has been achieved.17 18 19 20 The photodeoxygenation not only avoids toxic tin species, but also it is conducted in relatively benign solvents (2-propanol /water). In addition, the deoxygenation is carried out at room temperature or below, and benzoyl derivatives are attractive because of their easy synthetic access under mild and neutral conditions.TABLEPHOTOINDUCED ELECTRON-TRANSFER DEOXYGENATION OF BENZOATES AND m-(TRIFLUOROMETHYL)BENZOATES WITH 9-ETHYL-3,6-DIMETHYLCARBAZOLESubstrate Product and Yield9-Ethyl-3,6-dimethylcarbazole was previously synthesized in four steps beginning with the formylation of 9-ethylcarbazole to give 9-ethylcarbazole-3-carboxaldehyde which is now commercially available.21 Wolff-Kishner reduction, formylation of the 6-position, and a second Wolff-Kishner reduction gives DMECZ. The reported overall yield for the final three steps is 45%. The present procedure provides quantities of the desired compound in high overall yield by a shorter, more convenient sequence. The desired material was also prepared by a nickel-catalyzed cross-coupling of 3,6-dibromo-9-ethylcarbazole with methylmagnesium bromide (Corriu-Kumada coupling).22 23 3,6-Dibromo-9-ethylcarbazole was prepared by N-alkylation of commercially available 3,6-dibromocarbazole with diethyl sulfate . Alternatively, 3,6-dibromo-9-ethylcarbazole could be prepared by the bromination of 9-ethylcarbazole (Br 2, acetic acid , 0°C); however, this method also produced significant quantities of 1,3,6-tribromo-9-ethylcarbazole .Acknowledgments: This work was supported by Grant #DHP-172 from the American Cancer Society.This preparation is referenced from:z Org. Syn. Coll. Vol. 10, 246References and Notes1.Department of Chemistry and Center in Molecular Toxicology, VU Station B 351822, VanderbiltUniversity, Nashville, TN 37235-1822.2.Ambrose, J. F.; Carpenter, L. L.; Nelson, R. F. J. Electrochem. Soc. 1975, 122, 876;3.Barton, D. H. R.; McCombie, S. W. J. Chem. Soc., Perkin Trans. I 1975, 1574.4.Hartwig, W. Tetrahedron 1983, 39, 2609;5.McCombie, S. W. "Comprehensive Organic Synthesis"; Trost, B. M.; Fleming I., Eds.; PergamonPress: Oxford, 1991; Vol. 8, 811-833.6.Barton, D. H. R.; Subramanian, R. J. Chem. Soc., Perkin Trans. I 1977, 1718;7.Rasmussen, J. R.; Slinger, C. J.; Kordish, R. J.; Newman-Evans, D. D. J. Org. Chem. 1981, 46,4843;8.Robins, M. J.; Wilson, J. S. J. Am. Chem. Soc. 1981, 103, 932;9.Dolan, S. C.; MacMillan, J. J. Chem. Soc., Chem. Commun. 1985, 1588;10.Barton, D. H. R.; Blundell, P.; Dorchak, J.; Jang, D. O.; Jaszberenyi, J. C. Tetrahedron 1991, 47,8969;11.Oba, M.; Nishiyama, K. Tetrahedron 1994, 50, 10193.12.Saito, I.; Ikehira, H.; Kasatani, R.; Watanabe, M.; Matsuura, T. J. Am. Chem. Soc. 1986, 108,3115.13.Park, M.; Rizzo, C. J. J. Org. Chem. 1996, 61, 6092;14.Wang, Z.; Rizzo, C. J. Tetrahedron Lett. 1997, 38, 8177.15.Ambrose, J. F.; Nelson, R. F. J. Electrochem. Soc. 1968, 115, 1159.16.Prudhomme, D. R.; Wang, Z.; Rizzo, C. J. J. Org. Chem. 1997, 62, 8257. 17.Lopez, R. M.; Hays, D. S.; Fu, G. C. J. Am. Chem. Soc.1997, 119, 6949;18.Hadida, S.; Super, M. S.; Beckman, E. J.; Curran, D. P. J. Am. Chem. Soc.1997, 119, 7406;19.Barton, D. H. R.; Jacob, M. Tetrahedron Lett.1998, 39, 1331;20.Jang, D. O.; Cho, D. H.; Barton, D. H. R. Synlett1998, 39.21.Buu-Hoï, N. P.; Hoán, N. J. Org. Chem.1951, 16, 1327.22.Tamao, K.; Sumitani, K.; Kumada, M. J. Am. Chem. Soc.1972, 94, 4374;23.Corriu, R. J. P.; Masse, J. P. M. J. Chem. Soc., Chem. Commun.1972, 144.AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)9-Ethyl-3,6-dimethyl-carbazole:9H-Carbazole, 9-ethyl-3,6-dimethyl- (9); (51545-42-7)3,6-Dibromo-9-ethylcarbazole:Carbazole, 3,6-dibromo-9-ethyl- (8);9H-Carbazole, 3,6-dibromo-9-ethyl- (9); (33255-13-9)3,6-Dibromocarbazole:Carbazole, 3,6-dibromo- (8);9H-Carbazole, 3,6-dibromo- (9); (6825-20-3)Diethyl sulfate: H IGHLY TOXIC; CANCER SUSPECT AGENT:Sulfuric acid, diethyl ester (8,9); (64-67-5)[1,3-Bis(diphenylphosphino)propane]nickel(II) chloride: CANCER SUSPECT AGENT:Nickel, dichloro[trimethylenebis[diphenylphosphine]]- (8);Nickel, dichloro[1,3-propanediylbis[diphenylphosphine]-P,P'}- (9); (15629-92-2)Methylmagnesium bromide:Magnesium, bromomethyl- (8,9); (75-16-1)Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。
酸性离子液体催化合成草酸二乙酯
2011年第30卷第2期CHEMICAL INDUSTRY AND ENGINEERING PROGRESS ·407·化工进展酸性离子液体催化合成草酸二乙酯张淑新（淄博职业学院化学工程系，山东淄博 255000）摘要：合成了4种咪唑基酸性离子液体，用于催化草酸和乙醇酯化反应合成草酸二乙酯。
考察了影响反应的主要因素，确定最佳反应工艺条件为：采用[Mim(CH2)3SO3H]HSO4离子液体为催化剂，反应温度为110 ℃，反应时间为90 min，n(乙醇)∶n(草酸)=4∶1。
在此条件下离子液体循环使用4次，活性变化不明显，草酸二乙酯收率大于73%。
此外，采用溶胶-凝胶法将[Mim(CH2)3SO3H]HSO4离子液体固定到SiO2上，用于催化酯化反应。
结果表明，离子液体固定化后，其酸催化性能有明显提高，草酸二乙酯收率为84.8%，且催化剂具有较好的稳定性。
关键词：酸性离子液体；酯化反应；草酸二乙酯；固定化；溶胶-凝胶法中图分类号：TQ 028.32 文献标志码：A 文章编号：1000–6613（2011）02–0407–04 Synthesis of diethyl oxalate catalyzed by acidic ionic liquidsZHANG Shuxin（Department of Chemical Engineering，Zibo V ocational College，Zibo 255000，Shandong，China）Abstract：Four imidazolium-based acidic ionic liquids were synthesized and used as catalysts for the synthesis of diethyl oxalate by esterification of oxalic acid with ethanol. The effects of several operation conditions were investigated. The optimal reaction conditions were as follows：[Mim(CH2)3SO3H]HSO4 as catalyst，reaction temperature 110 ℃，reaction time 90 min，mole ratio of ethanol and oxalic acid 4∶1，under such conditions the yield of diethyl oxalate was over 73%，and the ionic liquid could be recycled at least four times without obvious deactivation. Additionally，the ionic liquid [Mim(CH2)3SO3H]HSO4 was immobilized on silica by the sol-gel method. The results showed that the supported ionic liquid exhibited higher catalytic performance than the unsupported one，with a yield of diethyl oxalate up to 84.8%.Key words：acidic ionic liquid；esterification；diethyl oxalate；immobilization；sol-gel method草酸二乙酯（DEO）是一种重要的医药中间体和精细化学品，主要用于医药苯巴比妥、硫唑嘌呤、羧苯酯青霉素等药物的合成，还可用于制造塑料促进剂、染料、显像管的制作工艺以及纤维素和香料的溶剂等。
草酸酯加氢铜基催化剂的关键技术和理论研究进展
草酸酯加氢铜基催化剂的关键技术和理论研究进展摘要：使用co催化耦联合合成草酸酯合成乙二醇已经成为研究中的热点，这一生产方式具有条件温和、原料丰富、成本低廉、原子利用率高、产品纯度高的特征，在这一技术中，核心技术就是草酸酯加氢催化剂，本文主要探讨草酸酯加氢铜基催化剂的关键技术和理论研究进展。
关键词：草酸酯加氢铜基催化剂关键技术理论研究一、引言乙二醇是一种化工中常用的有机化学原料，已经广泛的应用与塑料、防冻剂、聚酯纤维、橡胶、润滑剂、炸药等产品的生产中，用途十分的广泛。
就现阶段来看，生产乙二醇的方式是用石油合成法进行生产，即将乙烯氧化成环氧乙烷，再利用合成法得到乙二醇。
这种传统的生产方式能耗高、耗时长，随着能源问题的出现，迫切的需要寻求一种新的生成方式。
就我国的实际情况来看，石油资源贫乏、煤炭资源相对较为丰富，因此，可以开发一种使用煤炭资源作为原料来生产乙二醇的方法。
经过相关专家学者的研究，近年来也出现了一些新型合成乙二醇的方式，其中，使用co催化耦联合合成草酸酯合成乙二醇也成为研究中的热点，这一生产方式具有条件温和、原料丰富、成本低廉、原子利用率高、产品纯度高的特征，在这一技术中，核心技术就是草酸酯加氢催化剂，这一反应由几个一系列的反应构成：有关研究调查表明，铜基催化剂在该反应中的催化性能较为理想，因此本研究主要针对草酸酯加氢铜基催化剂的关键技术进行探究。
二、草酸酯加氢负载型铜基催化剂的载体效应铜基催化剂与其他的催化剂相比对于羰基加氢有着很好的选择性，适宜用在酯加氢反应之中，但是由于金属铜有着强度差、活性低、高温易烧结的特征，因此，一般使用负载型铜基催化剂来进行改性。
这种负载型催化剂有着硬度高、稳定性好的特征，能够有效提升活性组分的分散度，一般情况下，草酸酯加氢催化剂载体使用较多的有氧化硅、氧化铬以及分子筛等等。
最早应用在草酸酯加氢制乙二醇的催化剂时铜铬催化剂。
该种催化剂的反应温度是220℃，在1.5h-1相空速进行460h的反应，其活性仅仅只出现轻微的衰减，催化性能十分理想，但是由于铬具有一定的毒性，因此，新型无铬催化剂的开发也成为一个热点工作。
3_甲基_2_氧代丁酸的合成研究进展
［8］ Chang Chung － jang. Method for converting amino acids into ketone acids （ esters） ［P］. US：2003212293，2003 － 11 － 13.
CHEN Ai － jun，HE Guo － xin，LIU Sai （ Nanjing Lifenergy R ＆ D Co. ，Ltd. ，Jiangsu Nanjing 210016，China）
Abstract： 3 － Methyl － 2 － oxo － butanoic acid was a kind of bifunctional compound with special and active nature. It was an important intermediate for drug synthesis and biological transformation. And its calcium salt，as an effective drug，was used to treat urinary disease for many years. The main synthesis methods of 3 － methyl － 2 － oxo － butanoic acid were reviewed. Combining technological features，a detailed comparative analysis of preparation methods，suitable for industrial production，was supplied.
草酸二乙酯的生产工艺流程
草酸二乙酯的生产工艺流程英文回答：Production Process of Diethyl Oxalate.Diethyl oxalate is an organic compound that is commonly used as a reagent in organic synthesis. It is primarily produced through the esterification of oxalic acid with ethanol. The production process involves several steps, including preparation of the reactants, esterification reaction, separation and purification of the product.Firstly, the reactants, oxalic acid and ethanol, needto be prepared. Oxalic acid is typically obtained by the oxidation of carbohydrates or from ethylene glycol. Ethanol, on the other hand, can be derived from fermentation of sugars or from petroleum sources. Both oxalic acid and ethanol should be of high purity to ensure the quality ofthe final product.Once the reactants are ready, the esterification reaction can take place. This reaction is typically carried out in the presence of a catalyst, such as sulfuric acid or p-toluenesulfonic acid. The catalyst helps to speed up the reaction and increase the yield of diethyl oxalate. The reaction mixture is heated and refluxed for a certain period of time to allow the reaction to proceed.After the esterification reaction, the reaction mixture is cooled and the diethyl oxalate is separated from the by-products and unreacted starting materials. This can be done through various separation techniques, such as distillation or extraction. Distillation is commonly used to separate the diethyl oxalate from the reaction mixture, as it has a lower boiling point compared to the other components. The diethyl oxalate is collected as the distillate, while the by-products and unreacted starting materials are left behind.Finally, the collected diethyl oxalate undergoes purification to remove any impurities. This can be achieved through techniques such as recrystallization orchromatography. Recrystallization involves dissolving the diethyl oxalate in a suitable solvent and then allowing it to slowly crystallize out, leaving behind impurities in the solution. Chromatography, on the other hand, involves passing the diethyl oxalate through a column packed with a stationary phase, which separates the impurities based on their different affinities for the stationary phase.In conclusion, the production process of diethyl oxalate involves the esterification of oxalic acid with ethanol, followed by separation and purification of the product. The reactants are prepared, the esterification reaction is carried out with the help of a catalyst, and the diethyl oxalate is separated from the reaction mixture and purified. This process ensures the production of high-quality diethyl oxalate for various applications in organic synthesis.中文回答：草酸二乙酯的生产工艺流程。
药物合成反应课后翻译
1、216-224g(1.62–1.68 moles)的无水三氯化铝。
While the free-flowing catalyst is滴液漏斗缓慢滴加81g苯乙酰。
Considerable heat is evolved, and, if the drops of ketone are not dispersed, darkening or charring occurs. 放热反应，假如滴加的酮不能被分散，就会变黑或是碳化。
When about one-third of the acetophenone has been added, the mixture becomes a viscous ball-like mass that is difficult to stir.当三分之一的乙酰苯被滴加，反应混合物变成一个很难搅拌的粘性的球状团块。
Turning of the stirrer by hand or more rapid addition of ketone is necessary at this point. 在这时，改用手动搅拌或快速滴加酮是非常必要的。
The addition of ketone, however, should not be so rapid as to produce a temperature above 180°. 然而，速度不能太快，当反应温度超过180℃时。
Near the end of the addition, the mass becomes molten and can be stirred easilygrams of heavy dark residue by distillation at reduced pressure. 乙醚在常压下蒸馏，微量的溴苯乙酮通过减压蒸馏的方法从大量深色残渣中被分离出来。
The colorless distillate is carefully fractionated to obtain 94–100 g.通过分馏，得到无色的流出液94-100g2、反应式：3、2-Methyl-4-ethoxalylcyclopentane-1,3,5-trione. A solution of sodium ethoxide is prepared in a 2-l. three-necked, round-bottomed flask fitted with amercury-sealed stirrer, a reflux condenser carrying a drying tube, and a stopper by the addition of 69.0 g. (3 moles) of sodium to 950 ml. of absolute ethanol. 69.0g （3mol）钠和950ml无水乙醇在配有干燥回流冷凝管和汞封搅拌器的2L三口圆底烧瓶中制备乙醇钠。
211091464_超高效液相色谱串联质谱法测定乳制品中透明质酸
杜国辉，范维江，陈玉娟，等. 超高效液相色谱串联质谱法测定乳制品中透明质酸[J]. 食品工业科技，2023，44（8）：334−340. doi:10.13386/j.issn1002-0306.2022070057DU Guohui, FAN Weijiang, CHEN Yujuan, et al. Determination of Hyaluronic Acid in Dairy Products by Ultra-high Performance Liquid Chromatography-Tandem Mass Spectrometry[J]. Science and Technology of Food Industry, 2023, 44(8): 334−340. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2022070057· 分析检测 ·超高效液相色谱串联质谱法测定乳制品中透明质酸杜国辉1，范维江1，陈玉娟2, *，陈雯雯2，乔莉苹2，王萃玲3（1.山东商业职业技术学院食品工业产业学院，山东济南 250103；2.华熙生物科技股份有限公司，山东济南 250101；3.齐鲁医药学院，山东济南 250103）摘 要：本文建立一种超高效液相色谱-串联质谱（UPLC-MS/MS ）测定乳制品中透明质酸含量的分析方法。
样品经透明质酸酶降解，乙腈稀释，PRIME HLB 固相萃取柱净化，Waters BEH Amide （2.1 mm×100 mm ，1.7 μm ）酰胺柱分离，以0.2%氨水-乙腈（含0.2%氨水）为流动相梯度洗脱。
采用电喷雾离子源负离子模式扫描，多反应监测模式进行检测，外标法定量。
结果表明：乳制品中透明质酸在0.5~200 mg/kg 添加水平下回收率为91.4%~106.2%，RSD 为2.3%~6.7%。
草酸二乙酯鉴别方法
草酸二乙酯鉴别方法英文回答：Identification of Diethyl Oxalate.Diethyl oxalate, also known as ethyl oxalate or oxalic acid diethyl ester, is a colorless liquid with a fruity odor. It is commonly used as a solvent and in organic synthesis. There are several methods to identify diethyl oxalate, including physical properties, chemical reactions, and spectroscopic analysis.1. Physical Properties:Diethyl oxalate has a boiling point of 185-186°C and a melting point of -25°C. These values can be determined using a thermometer and a melting point apparatus. Additionally, the density of diethyl oxalate is 1.08 g/mL at 20°C, which can be measured using a density meter or hydrometer.2. Chemical Reactions:Diethyl oxalate can undergo various chemical reactions that can be used for identification. For example, it reacts with concentrated sulfuric acid to form carbon monoxide gas and ethyl sulfate. This reaction can be observed by the evolution of gas and the formation of a white precipitate.Another reaction involves the reaction of diethyl oxalate with potassium permanganate in acidic medium. This reaction produces carbon dioxide gas, water, and manganese(II) ions. The presence of carbon dioxide gas can be confirmed by the effervescence or bubbling observed during the reaction.3. Spectroscopic Analysis:Diethyl oxalate can be analyzed using spectroscopic techniques such as infrared spectroscopy (IR) and nuclear magnetic resonance (NMR) spectroscopy. IR spectroscopy can be used to identify the functional groups present in thecompound by analyzing the absorption bands in the infrared region. NMR spectroscopy provides information about the connectivity of atoms in the molecule and can be used to confirm the structure of diethyl oxalate.For example, in the IR spectrum of diethyl oxalate, a strong absorption band around 1720 cm-1 indicates the presence of the carbonyl group (C=O). The NMR spectrum shows peaks at chemical shifts around 4.0-4.2 ppm, which correspond to the ethyl (CH2CH3) groups.In conclusion, there are several methods to identify diethyl oxalate, including physical properties, chemical reactions, and spectroscopic analysis. By analyzing the boiling point, melting point, density, and conducting chemical reactions such as with sulfuric acid and potassium permanganate, as well as using spectroscopic techniqueslike IR and NMR spectroscopy, diethyl oxalate can be accurately identified.中文回答：草酸二乙酯鉴别方法。
药物合成反应 (第三版 闻韧) 课后答案Chapter 3 Acylation Reaction
O
O
O
CHO OH (4)
CN O N Ph CN O N Ph N
OH
H (5) N
H3C
CH3
O (6)
N
N
N CO2CH3 CO2CH3
O CO2CH3
H3CO (7) H3CO NHCOCH3
H3CO H3CO N CH3
H3CO H3CO N CH2
《药物合成反应》 （第三版） 闻韧主编
习题及答案
第三章 酰化反应习题及答案
1. 根据以下指定原料、试剂和反应条件，写出其合成反应的主要产物
OH O O
(2) C17H35COOC2H5 + (COOC2H5)2 C2H5ONa heat C2H5OH
(1)
+ Cl
O Cl
Et3N/CH2Cl2
OH (4) OH O (5) S
CH2OH O (6) OH H OH H OH NHAc
O + NaOH Cl Cl
+
POCl3 Ph N CH3 H
H CH COCl 3 CHCl3
(7) HO
O O (8) +
AC2O/Py
NaH/PhH C2H5O OC2H5
(3)
HO N H
O
O
O N H OH
Org. Synth., 2006, 83: 97.
(4)
O O
(5)
S CHO CH2OAc O OAc OAc H H Cl NHAc H
(6)
(7)
AcO
(8)
O CO2Et
西弗碱配合物的合成及表征
L-谷氨酰胺席夫碱配合物的合成及其结构解析摘要席夫碱亦被称作西佛碱（Schiff base），其特有的官能团为亚胺或甲亚胺基（—RC=N—）。
席夫碱是活性羰基和氨基通过化学反应缩合而成的产物，可作为有机试剂、液晶材料、磁学材料等在医药抗肿瘤、抗病毒、抑菌、荧光、色谱分析等领域均得到了广泛的应用并取得了巨大的进展[1]。
而L-谷氨酸是生命体重要的氨基酸，其在自然界中有着广泛的存在。
L-谷氨酰胺的锂盐与草酸二乙酯以及大茴香醛所形成的配位化合物亦具有席夫碱在药理学和生理活性上良好的表现。
在本文中主要介绍L-谷氨酰胺的钾盐、锂盐与草酸二乙酯、大茴香醛所形成的配体其与多种金属盐特别是铜盐所形成的配合物的结构及药理特性。
通过借助化学软件ChemcalDraw，oringe等对其进行结构分析和红外谱图的分析，对其结构特性进行表征[2]。
以下为实验工作过程：（1）L-谷氨酰胺为主的配体与多种金属盐离子形成多样的金属配合物.通过查阅资料和借助化学仪器得知L-谷氨酰胺所形成的配体在不同的反应条件下所形成的配合物亦不相同，而本文主要介绍其配体与金属盐离子按照1:1的比例进行反应，羰基失质子与铜、镍、锌等金属离子结合，α-氨基与金属盐离子以共价键的形式结合所形成的配合物。
（2）L-谷氨酰胺与氢氧化锂或氢氧化锂反应所形成的盐与以草酸二乙酯和大茴香醛等有机物反应形成配体，在通过探索配体与铜、镍、锌、镁等金属盐在一定条件下形成金属配合物。
通过红外光谱分析、元素分析和借助抗菌试验等对合成的配合物进行表征和分析。
关键词：L-谷氨酰胺草酸二乙酯大茴香醛配体Schiff base配合物铜、锌、镁金属盐Abstrac tL-glutamine Schiff base complexes Synthesis and structural analysis thereofSchiff bases are also known as Schiff base (Schiff base), its unique functional groups imine or azomethine (-RC = N-). Schiff base is a product of reactive carbonyl groups and amino condensation formed by a chemical reaction can be used as organic reagents, liquid crystal materials, magnetic materials, etc. in the pharmaceutical anti-tumor, anti-viral, antibacterial field, fluorescence, chromatography, etc. have been widely application and has made tremendous progress. And L-glutamic acid is an important amino acid beings, which has been widely exist in nature. L-glutamine coordination compounds with lithium diethyl oxalate salt and anise aldehyde formed Schiff base also has the pharmacological and physiological activity of a good performance.In this article describes the structure and the pharmacologicalproperties of the ligand L-glutamine potassium, lithium diethyl oxalate, anisic aldehyde formed with various copper salts, especially the formed complexes . By means of chemical software ChemcalDraw, oringe be analyzed, such as structural analysis and infrared spectra, and its structural properties were characterized. The following is an experimental work processes:(1)L-glutamine-based ligands with various metal ions to form avariety of metal complexes by means of chemical equipment and access to information that the ligand L-glutamine formed at different reaction conditions under the complex formed is not the same, and this paper describes its ligand and metal ions react in accordance with the ratio of 1:1, in combination with proton loss carbonyl copper, nickel, zinc and other metal ions, α-amino and salt ion in the form of covalently binding complexes formed.（2）L-glutamine and lithium hydroxide or lithium hydroxide, salts formed by reaction with diethyl oxalate and anisic aldehyde to form organic ligand and the ligand by exploring copper, nickel, zinc, magnesium salts under certain conditions form metal complexes.By infrared spectroscopy, elemental analysis and antimicrobial testing and other means of synthesized complexes were characterized and analyzed.Keywords: L-glutamine Anisaldehyde diethyl oxalate ligand Schiffbase complexes of copper, zinc, magnesium salts第一章绪论1.1氨基酸的介绍及其研究意义氨基酸是含有氨基的羧酸，氨基酸分子中同时具有羰基和氨基，是组成蛋白质必不可少的一类有机化合物。
Synthetic approaches to the 2002__ new drugs
Keywords: Synthesis, New Drug, New Chemical Entities, Medicine, Therapeutic Agents. INTRODUCTION Dozens of new drugs are registered and launched every year around the world. Although thousands of drugs have been marketed historically, the structure similarity among some drugs is obvious and even more so for drugs targeting in the same gene family. Furthermore, it has been demonstrated that molecules which share the same or similar chemical template can be further modified for different therapeutic indications against the similar gene family. Therefore, medicinal chemists, being aware of these new drug structures, can strike and adopt ideas for their own innovations. In addition, preparation of these drug molecules has been studied extensively to make it concise due to the cost of goods consideration and to ensure environmentfriendliness. Having such robust and reliable synthetic methods in hand to access these core structures will steer synthetic efforts more effectively toward the most promising compounds and help focus the optimization toward other challenging properties such as ADME. In 2002 alone, 33 NCEs including biological drugs, and two diagnostic agents reached the market [1-5]. This review article will focus on the syntheses of the 28 new drugs marketed last year (Figure 1), but excludes new indications for known drugs, new combinations and new formulations. The syntheses of these new drugs were published sporadically in different journals and patents. It is our intention to compile the syntheses of new drugs yearly into an annual review for the readers’ advantage. The synthetic routes cited here represent the most scalable methods according to the best of the authors’ knowledge and appear in alphabetical order by generic name. Adefovir Dipivoxil (HepseraTM) Adefovir dipivoxil (1), discovered by Gilead, became the first nucleoside analogue to gain FDA approval for the treatment of chronic hepatitis B infection [6]. Adefovir works by blocking viral replication [6]. The synthesis [7,8] of adefovir dipivoxil (1) involves a four-step process [9,10] as depicted in Scheme 1. Adenine (29) was condensed with ethylene carbonate (30) in hot DMF to afford intermediate 9*Address correspondence to these authors at the Pfizer, Groton, CT 06340, USA; Tel: 1-860-7153552; E-mail: jin_li@; kevin_k_liu@ 1389-5575/04 $45.00+.00
【doc】豆蔻酰化富丙氨酸激酶C底物与气道黏液分泌
豆蔻酰化富丙氨酸激酶C底物与气道黏液分泌国外医学呼吸系统分册2005年第25卷第11期SectRespirSysForeignMedSci,Nov.2005,V o1.25.No.11豆蔻酰化富丙氨酸激酶C底物与气道黏液分泌邓治平文富强冯玉麟气道黏液是由气管,支气管杯状细胞及黏膜下腺体分泌的黏性胶状液体,构成气道表面液体层,覆于气道黏膜表面,起到润滑,保湿和气道保护作用.可吸附吸人的粉尘颗粒,碎屑,衰老细胞以及细胞产物,随后被黏液纤毛运输系统清除,维持正常下呼吸道在生理状态时的无菌状态.在病理情况下,多种因素可导致气道黏液分泌异常及呼吸道黏液纤毛清除功能障碍,使管腔阻塞以及呼吸道细菌定植,引起多种呼吸道疾病.气道黏液高分泌是多种呼吸道疾病如慢性支气管炎,支气管哮喘和肺囊性纤维化等疾病的重要的病理生理特征.豆蔻酰化富丙氨酸激酶C底物(myristoylated alanine—richCkinasesubstrate,MARCKS),是蛋白激酶C(ProteinkinaseC,PKC)主要的底物蛋白之一,在细胞迁移及黏附,细胞内吞及胞吐作用,细胞吞噬及神经内分泌等细胞骨架蛋白依赖性过程中起重要作用_】].现已证实MARCKS是黏液分泌过程中关键的蛋白分子_2.],因而以MARCKS为靶点在黏液高分泌治疗中越来越受到重视.1MARCKS的结构MARCKS是一种膜结合蛋白,相对分子质量80～87ku,是一种结构较简单的伸展性蛋白,可形成a螺旋,但没有三级及四级结构,不能形成疏水的核心.至少含有两个高度保守的区域,即氨基末端(N末端)结构域和效应结构域(effectordomain,ED).在N末端区域有一个含14个碳原子的饱和脂肪酸链(肉豆寇酸),通过酰胺键与N末端的甘氨酸残基相连接.ED区域有5个疏水的苯丙氨酸残基,有13个带正电荷的碱性氨基酸(赖氨酸及精氨酸)残基及4个供PKC磷酸化的丝氨酸残基,使得ED区域带正电荷,可与带负电荷的膜脂质分子(如磷酸肌醇等) 相互吸引,豆寇酰化链可籍其疏水作用插入脂质双分子层膜中,此外,5个疏水的苯丙氨酸残基与膜磷脂双分子头亦可形成疏水作用,通过这三种作用方式使得MARCKS结合于脂质双分子层膜上口],但MARCKS至少具备前两种作用方式才能与膜结合.作者单位:610041成都,四川大学华西医院呼吸科MARCKS主要分布于细胞膜的胞浆侧,尤其与细胞膜上的4,5一二磷酸肌醇(PIP2)高亲和力的结合,不仅有助于MARCKS锚定于细胞膜,而且可以将能与PIP2高亲和力结合的丝状肌动蛋白(filametous-actin,F—actin)与PIP2分隔开l_4]. MARCKS可结合钙调素(CaM)和F—actin,且在PKC和活化CaM(CaM—Ca.)的竞争性调控下与丝状肌动蛋白交联,MARCKS由此将细胞内PKC和CaM两大信号传导途径联系起来,在涉及细胞骨架蛋白的细胞活动过程中有重要的意义.2气道黏液的结构及组成气道黏液是一种非均一黏弹性的黏性胶,95以上为水分,黏蛋白(Mucin)是黏液最重要组分,相对分子质量在0.3~32ku,它决定了气道黏液主要的流变学特性.根据修饰体结构的不同,黏蛋白可分为两大类:膜相关性黏蛋白和分泌性黏蛋白_5],前者包括MUC1,MUC3A,MUC3B,MUC4,MUC9, MUC11,MUC12和MUC14,后者包括MUC2, MUC5ACMUC5B,MUC6MUC7MUC8MUC10.气道的分泌性黏蛋白主要为MUC5AC,MUC5B和MUC2.目前认为膜相关性黏蛋白在细胞间相互作用过程中起着重要的作用,如细胞黏附,细胞识别,信号传导,肿瘤细胞的侵袭和转移等.分泌性黏蛋白分布于胃肠道,呼吸道,泌尿生殖道表面的黏液中,这些黏液的主要功能是起润滑作用,同时也是机体重要的防御机制之一.2.1黏蛋白与多糖黏蛋白是一种高度糖基化的糖蛋白,是由含有一条到上百条糖链的蛋白质核心(Apomucin)与糖类以共价键结合形成的复合物,含糖量在70～809/6左右,黏蛋白的糖基的组成决定黏液的理化特性].Apomucin含有丰富的带羟基侧链的氨基酸残基(丝氨酸以及苏氨酸残基),是糖链与蛋白质结合的位点.气道黏蛋白分子的糖链通过O一连接型或N一连接型糖苷键与多肽链氨基酸残基相连,前者为主要的连接方式,可以分为核心结构,骨架和非还原端三部分,如下图所示:国外医学呼吸系统分册2005年第25卷第11期SectRespirSysForeignMedSei,Nov.2005,V o1.25.No.11图1黏蛋白连接型糖链模式图2.2黏蛋白核心Apomucin含有较多以0一型糖苷键与核心糖结构相连的丝/苏氨基酸残基,编码该区域的基因含有重复序列(即可变数目的串联重复, variable—numbertandemrepeats,VNTRs),不同的黏蛋白的VNTRs长度和数量不同,并在转录过程中发生选择性剪切,因而从一个基因可得到不同的信使RNA(mRNA)转录体,进而每种黏蛋白转录体通过各种翻译后修饰可产生不同的多肽.N一乙酰氨基半乳糖通过初级7—0一糖苷键与蛋白核心的丝氨酸或苏氨酸相连,从而启动低聚糖链延长和分支.这些机制决定了黏蛋白的多样性.同时抗原决定簇大多集中在此区域,单克隆抗体与黏蛋白反应亦主要作用在其VNTR位点上l_7].3MARCKS与黏液的分泌涉及气道黏液分泌过程十分复杂,具体作用环节尚未完全明确.黏蛋白核心在杯状细胞及黏液分泌细胞中的粗面内质网合成后,进入高尔基复合体进行糖基化,形成0一连接的寡糖链,然后在细胞内浓缩,包被以细胞内膜,形成分泌颗粒并贮存于胞浆中.在分泌相关的细胞信号传导途径的精细调控之下,最后经胞吐作用释放到胞外黏膜面.业已证实,MARCKS是气道黏液分泌机制中关键的蛋白分子.3].主要有以下几方面证据:①Li等]用MARCKS特异的反义寡核苷酸链同正常人支气管上皮细胞(NHBEC)孵育,不仅减少了NHBEC的MARCKS蛋白水平,而且明显地减少了由佛波脂(PMA)和8一溴一环鸟嘌呤单核苷酸(8-Br- cGMP)所诱导的NHBEC的黏液分泌;PMA及8一Br-cGMP可分别激活NHBEC的PKC和PKG而诱导黏液分泌.②MARCKS蛋白ED的磷酸化位点区域(phosphorylationsitedomain,PSD)是该蛋白的PKC作用位点.应用MARCKS的cDNA,先切除PSD相应的脱氧核苷酸序列后,再转染NHBEC明显抑制了PMA及8一Br—cGMP诱导的黏液分泌l_2].③MARCKS的豆寇酰化N末端序列(MyristoylatedN—terminalSequence,MANS)是MARCKS蛋白N末端含24个氨基酸的肽链,并且第一个甘氨酸残基豆蔻酰化,是MARCKS必备的与膜结合的结构基础之一,可介导MARCKS与膜的结合.与上述肽链的氨基酸组成一致但氨基酸序列为随机组合的肽链称为随机组合序列(randomN—terminalSequence,RNS),用MANS和RNS同NHBEC孵育后,发现MANS抑制了PMA及8一Br—cGMP诱导的黏液分泌,且呈浓度依赖性地抑制,而作为对照的RNS不抑制PMA及8一Br—cGMP诱导的黏液分泌[2].④Singer等[8用MARCKS相关多肽(MANS)阻断了卵蛋白诱发小鼠哮喘模型的黏液分泌,且呈剂量依赖性,而RNS不抑制卵蛋白诱发小鼠哮喘模型的黏液分泌.综合以上的证据,确定了MARCKS是黏液分泌机制中关键的蛋白分子,推测其作用机制为以下过程:气道杯状细胞受刺激时:①激活PKC后使MARCKS的ED区域中的丝氨酸残基磷酸化,ED上的正电荷被中和,MARCKS从细胞膜胞浆侧脱落并转位至胞浆内.位于胞膜被MARCKS分隔的PIP2随即暴露并与F—actin高亲合力地结合将F—actin的一端附于胞膜l_】].②转位至胞浆内的磷酸化MARCKS被蛋白磷酸酶2A(PP2A)脱磷酸后又恢复其与膜和F—actin结合的特性,再结合于包被黏蛋白颗粒的细胞内膜以及F—actin,从而将黏蛋白颗粒与具有收缩性的细胞骨架蛋白(F—actin等)联接起来,此时F-actin的一端附于胞膜内侧,另一端通过MARCKS与黏蛋白颗粒相连.F—actin收缩将黏蛋白颗粒移向细胞周边并与细胞膜融合,然后通过胞吐作用(exocytosis)将黏蛋白颗粒泌出胞外_2].体内外实验中用MARCKS相关多肽(MANS)均可呈浓度依赖性地阻断黏液分泌,而RNS肽链则无此作用,且Singer等进一步证实MANS只是阻断黏液分泌过程而使黏液贮留于胞内,并不减少黏液的产生.推测其机制是由于外源性MANS竞争性抑制了内源性MARCKS与黏蛋白颗粒膜的结合,从而阻断了黏蛋白分泌,而RNS不抑制内源性MARCKS与黏蛋白颗粒膜的结合则不能阻断黏蛋白分泌.在致死性哮喘患者的气道中急慢性炎症并存,杯状细胞数量及黏蛋白合成明显增加,炎症渗出物,坏死脱落上皮以及增多的黏液形成黏液栓,阻塞气道,尤其是杯状细胞急性脱颗粒释放黏液是造成哮喘急性恶化和死亡的重要原因I9].基于上述机制,以MARCKS为作用靶点逐渐成为黏液高分泌治疗研究的方向之一,并且越来越受到重视l_3].(下转第867页)国外医学呼吸系统分册2005年第25卷第11期SectRespirSysForeignMedSci,Nov.2005,V o1.25.No.11?867? 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DonaldsonGC,SeemungalTAR,BhowmikA.eta1.Relationship betweenexacerbationfrequencyandlungfunctiondeclinein chronicobstructivepulmonarydisease.Thorax,2002,57:847—852.SportelJH,KoeterGH,vanAhenaR,eta1.Relationbetween beta—lactamaseproducingbacteriaandpatientcharacteristicsin chronicobstructivepulmonarydisease(COPD).Thorax,l995, 5O:249-253.(收稿日期:2004—1l—l5)(上接第863页)综上所述,涉及气道黏液及黏蛋白分泌的一系列过程十分复杂,目前远未阐明.黏蛋白基因的转录及其调控,翻译及翻译后修饰,黏蛋白颗粒的包装等过程亦不甚明确.现已证实在黏蛋白颗粒由胞浆泌至胞外这一过程中MARCKS是关键的蛋白分,子,是黏液分泌相关的细胞内外信号传导途径最终作用点,从而有助于气道黏液高分泌的治疗及相关药物的开发.34参考文献ArbuzovaA,SchmitzAP,V ergersG.Cross—talkunfolded: MARCKSproteins.BiochemJ,2002.362(pt1):1—12.IiY,MartinID.SpizzG.eta1.MARCKSproteinisakey moleculeregulatingmucinsecretionbyhumanairwayepithelial cellsinvitro.JBioChem,2001,276(44):40982—40990. 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齐墩果酸衍生物的合成及其抗癌活性的研究
第1期
张蓬勃，等:齐墩果酸衍生物的合成及其抗癌活性的研究
27
1.2.4 2,3 -甲氧酯基-齐墩果酸酰氯(4)的 制备
将2,3 -甲酯基-齐墩果酸(1 g, 1.89 mmol)溶于20 mL干燥二氯甲烷溶液中,冰浴条 件下缓慢滴加草酰氯(1. 19 g,9. 43 mmol) ,0. 5 h后撤冰,40 °C下反应2h, TLC监测反应.反应 结束后蒸发有机溶剂，干燥环己烷冲洗3次，蒸 发得白色固体化合物2,3 -甲氧酯基-齐墩果 酸酰氯0.98 g,产率98 %. 1.2.5化合物「-匚的制备 1.2.5. 1化合物I】的制备
实验步骤同化合物I 1.2,3 -甲氧酯基-齐 墩果酸酰氯(0. 15 g,0. 274 mmol)与对甲基苯胺 (0. 148 g,1. 37 mmol)反应，得白色固体化合物 1 2 0. 079 g,产率 52.6 % , mp 185 ~ 188 C. 1H - NMR ( 600 MHz, CDC13) , 3：7. 57 ~ 7.52 (2H,m,ph -H -2,H -6) ,7. 15 ~7.07(2H,m, ph - H - 3, H - 5),6. 50 (1H, t, J =5.4 Hz, CONH) ,5. 38(1H,t, J = 3.4 Hz,H - 12),3. 57 (3H, s, 2 - COOCH3 ) , 3. 56 ( 3H, s, 3 COOCH3) ,2. 33(3H,d, J = 9.2 Hz,ph - CH3), 1.21(6H, s, H -23、H -24),1.01(3H, s, H -
图1齐墩果酸衍生物的合成路线
Fig. 1 Synthesis of oleanolic acid derivatives
吲唑的简便合成
化学试剂,2007,29(1),53～54吲唑的简便合成蔡可迎3,宗志敏,魏贤勇(中国矿业大学化工学院,江苏徐州 221008)摘要:以邻硝基甲苯为原料,在乙醇钠催化下与草酸二乙酯缩合,然后经水解、双氧水氧化、盐酸酸化得到邻硝基苯乙酸,收率62%。
邻硝基苯乙酸用8%硫化铵溶液在回流温度下还原2h 后再进行重氮化反应,将得到的重氮盐溶液于室温放置24h 得到吲唑,收率71%。
两步总收率44%。
关键词:吲唑;邻硝基苯乙酸;合成中图分类号:O626 文献标识码:A 文章编号:025823283(2007)0120053202收稿日期:2006205225基金项目:江苏省高新技术产业发展项目(J H B05233)。
作者简介:蔡可迎(19702),男,江苏沛县人,博士生,讲师,从事有机中间体的合成研究。
吲唑是重要的有机合成中间体,其许多衍生物具有药物活性[123]。
例如,吲唑环在Cu (Ⅱ)催化下与芳基硼酸反应可得12芳基吲唑[4],12芳基吲唑可作避孕药[5];吲唑与酸酐或酰氯反应可得N 2酰基吲唑[6],其中一些N 2酰基吲唑具有驱虫活性。
吲唑的合成方法主要有:1)以吲唑232羧酸为原料进行脱羧反应得到[7];2)以32腈基吲唑为原料进行脱腈基反应得到[7];3)以32氯吲唑为原料经脱氯得到[8];4)邻甲基苯胺与乙酐、醋酸钾和亚硝酸异戊酯的混合物料反应得到[9];5)42醛基吡唑与丁二酸二乙酯在叔丁醇钾催化下缩合得到[10]。
方法1)、2)和3)的问题是原料不易获得;方法4)的反应体系复杂,导致后处理困难,收率低;方法5)需在强碱催化下进行,条件苛刻。
以价廉易得的邻硝基甲苯为原料,在乙醇钠催化下与草酸二乙酯进行缩合反应,再经水解、氧化及酸化制得邻硝基苯乙酸,后者通过还原、重氮化、环合及脱羧可得到吲唑:1 实验部分111 主要仪器与试剂惠普HP 6890/5973型气相色谱/质谱联用仪;美国Nicolet 公司Magna 2IR 560红外光谱仪。
维生素B1催化酰化反应
摘要近年来对药物型催化剂的研究很多，尤其是对维生素C作为催化剂的研究已有很多相关报道。
此类催化剂无毒，无污染，易得，高效等特点是符合绿色环保概念的，是我们工业生产所需要的，开发研究此类催化剂的应用范围是非常有必作为催化剂来催化乙酸叔丁酯的合成。
乙酸叔丁酯的要的，我们尝试应用维生素B1制备可以用具有亲核作用的催化剂，也可以用一些路易斯酸作为催化剂，但是这些催化剂存在制备复杂，价格较高，不易回收利用，环保程度不够等问题。
我们作为催化剂从而克服以上缺点，这方面的研究目前还未见报道。
应用维生素B1本实验应用维生素B作为催化剂，首先对催化剂进行了差热-热重表征，然后1用此催化剂催化合成乙酸叔丁酯，并通过实验考察了反应时间，反应温度，催化作为催剂用量和酐醇的摩尔比对产品产率的影响。
实验研究结果表明，维生素B1化剂有着较好的催化活性和应用前景。
当反应条件为：反应时间 5 h ,反应温度60 ℃，酐醇摩尔比 1：1.1，催化剂用量 0.8 g时，乙酸叔丁酯的收率可达88.4％。
产品经红外光谱、核磁共振进行了分析，且通过气相色谱分析得知产品纯度较高。
关键字：乙酸叔丁酯，维生素B1，酰化反应AbstractIn recent years, the study of drug catalyst for many, especially in vitamin C as a catalyst has a lot of relevant reports. The catalyst characteristics of non-poisonous，non-pollution, easy to get and efficient are fit for the green environmental protection concept and industrial production requirements, it is very necessary to research and development the scope of application of these catalysts. Synthesis tert-butyl acetate we can use nucleophilic function catalyst, also we can use some Lewis acid as a catalyst, but these catalysts are complicated preparation, high price, difficult to recycle, or environmental protection degree is not enough. So our purpose is use vitamins B1 as the catalyst to overcome these shortcomings.This experimental use of vitamin B1as a catalyst, which was characterized by TG-DTA. Then tert-butyl acetate was synthesized using the catalytic, we have investigated that the effects of reaction time, reaction temperature, catalyst amount, anhydride /alcohols molar ratio to reaction yield. The results showed that choose vitamin B1as catalyst have better catalytic activity and application. The experiment results showed that the best of reaction condition are as follows: reaction time is 1.5 h, reaction temperature is 60 ℃, anhydride /alcohols molar ratio is 1:1.1, catalyst amount is 0.8 g, the yield of tert-butyl acetate could come up to 88.4 %. The products was analyzed by IR, 1H-NMR and GC which analysis products with high purity.Keyword：tert-butyl acetate, vitamin B1, acylation reaction目录1 前言 (1)2 文献综述 (3)2.1 乙酸叔丁酯的简介 (3)2.1.1 乙酸叔丁酯的制备方法 (3)2.1.2 乙酸叔丁酯的表征 (7)2.2 维生素系列在有机合成中的良好催化作用 (7)2.2.1 维生素简介 (7)2.2.2 维生素C催化剂的简介 (8)2.2.3 维生素C的催化作用 (9)2.2.4 维生素C含量的检测 (11)的催化作用 (12)2.2.5 维生素B122.2.6 维生素E的催化作用 (14)2.3 维生素B的简介 (14)1物理性质简介 (14)2.3.1 维生素B12.3.2 维生素B的制备方法 (15)1的化学结构式 (15)2.2.3 维生素B1在生物体内的催化作用 (16)2.2.4 维生素B1在安息香缩合反应中的催化作用 (17)2.2.5 维生素B1催化安息香缩合的催化机理 (20)2.2.6 维生素B1含量的检测 (21)2.2.7 维生素B12.2.8 维生素B的的新用途 (22)13 实验部分 (25)3.1主要试剂及仪器 (25)3.2 实验方法 (25)3.2.1 维生素B的热分析 (25)13.2.2 乙酸叔丁酯的催化合成 (26)3.3 结果与讨论 (27)对叔丁醇脱水的影响 (27)3.3.1 维生素B13.3.2 反应时间对酯收率的影响 (27)3.3.3 催化剂用量对酯收率的影响 (28)3.3.4 反应温度对酯收率的影响 (28)3.3.5 乙酸酐与叔丁醇的摩尔比对酯收率的影响 (29)3.3.6 乙酸叔丁酯的红外分析 (30)3.3.7 乙酸叔丁酯的核磁共振分析 (31)3.3.8 乙酸叔丁酯的气相色谱分析 (31)4结论 (33)致谢 (34)参考文献 (35)维生素B1催化酰化反应1 前言乙酸叔丁酯是一种工业上优良的汽油抗爆添加剂，可用作合成中间体、保护剂、萃取剂等，如：氨基酸保护剂、安普那韦中间体、紫杉醇萃取剂等；也用作硝酸纤维素的溶剂；还可用作涂布热塑性基材如：聚异氰酸酯涂料、聚氨酯涂料、溶剂性油墨等；还可又做航空、航天工业机械，精细机械设备的清洗剂等。
DMAP催化合成白藜芦醇烟酸酯
第25卷第2期宿州学院学报Vol .25,No .2 2010年2月Journal of Suzhou University Feb .2010doi :10.3969/j .issn .1673-2006.2010.02.012DMAP 催化合成白藜芦醇烟酸酯刘耀武, 金传山(安徽中医学院药学院,安徽省现代中药重点实验室,安徽合肥 230032)摘要:目的:以烟酸、白藜芦醇为原料,采用DM A P 催化合成方法制备白藜芦醇烟酸酯,期望寻找优化的白藜芦醇烟酸酯合成路线。
方法:以烟酸、白藜芦醇为起始原料,经酰氯化、D M AP 催化成酯等反应,得到目标化合物。
结论:通过本实验工艺路线合成白藜芦醇烟酸酯,产率90.3%,成酯反应时间比传统方法缩短一半。
产物经过IR 、1H -N M R 等进行了表征。
关键词:白藜芦醇;白藜芦醇烟酸酯;DM A P 催化中图分类号:O 621.25+1 文献标识码:A 文章编号:1673-2006(2010)02-0039-03收稿日期:2009-09-23作者简介:刘耀武(1975-),安徽亳州人,讲师,硕士研究生,主要研究方向:中药资源活性成分的开发与利用。
引言 白藜芦醇(Res)又称芪三酚,是一种含有芪类结构的非黄酮类多酚化合物[1],有顺式和反式两种存在形式,研究表明白藜芦醇具有防癌抗癌、降血脂、抗血小板聚集、激活Sirtuins 抗衰老酶、抗氧化、抗自由基、抗过敏、抗菌消炎、抗骨质疏松、护肤增白等多种有益的生理活性[2-4]。
但是白藜芦醇本身易氧化,t 1/2时间短,极大地限制了其开发与使用。
烟酸又称维生素B 5,俗称尼古丁酸,是吡啶类衍生物,水溶性强,它具有参与生物体内的氧化还原,促进新陈代谢的作用[5-6]。
根据药物设计拼合原理,张学景等以三乙胺催化合成了白藜芦醇烟酸酯,将白藜芦醇和烟酸进行酯化,对白藜芦醇进行了修饰改造,但试验发现单纯使用三乙胺催化合成反应时间4～6h [7]。