溴十一烷的合成

2008年第39卷第3期《浙江化工》文章编号: 1006 4184(2008 )03 0005-02溴十-烷的合成杨鑫骥|2,沈德隆',翁建全',蔡启军,金剑锋1(1.浙江工业大学化学工程与材料学院,浙江杭州310014;2浙江嘉兴学院医学院,浙江嘉兴314001)摘要:以月桂酸和 N-溴代琥珀酰亚胺为起始原料经Cristol sT反应得到澳十一烷。考查了投料比、反应温度、反应时间等实验因素对产物收率的影响。经过优化，较佳的工艺条件为:月桂酸和N-溴代琥珀酰亚胺的摩尔比为1:1.2,反应温度609C, 反应时间3h。溴十一烷收率为60%,含量98%。产品结构经IR、'H-NMR和MS表征确认。关键词:月桂酸;N-溴代琥珀酰亚胺;溴十一烷;Cristol ST反应溴代烃是有机合成中的重要中间体。澳十一烷,上改进采用月桂酸和N-溴代琥珀酰亚胺(NBS)作英文通用名:1-bromoundecane,无色液体，沸点为起始原料合成了溴十一烷,并对其工艺进行了优137~138C( 18mmHg),广泛应用于直链芳烃及有机化,收率和液溴相比稍高。试剂等合成中1+。按起始原料分,其合成路线主要1实验部分有以下几条:1.十二醇和三溴化磷路线]:2.十二醛1.1主要仪器及试剂与一溴三氯甲烷路线;3.十二酸与溴路线;4十二Mercury Plus- 400型核磁共振仪,CDCl3作溶剂,酸乙酯与三溴化磷路线问。路线1和4收率比较低,TMS为内标; Bruker Vector 22型红外光谱仪,采用实验条件要求比较高,路线2原料比较贵,需用到液膜法;HP5989B质谱仪;GC900A型气相色谱仪，的试剂多。路线3反应条件温和,收率高,但是反应氢火焰检测器。实验中所用试剂皆为市购分析纯。所用的溴化剂是液溴,有易挥发强腐蚀性和局部过1.2反应过程浓导致副反应多的缺点。本文作者在路线3的基础反应过程: .C.H2.COOH +N-Brcatalyzer 、C.jH2Br +N-H + CO21.3实验过程盐水洗,取有机层,用无水硫酸钠千燥。过滤脱溶,在装有恒压滴液漏斗、温度计、冷凝管和机械得浅黄 色(近乎无色)液体,减压蒸馏(8毫米汞柱),搅拌的150mL四口圆底烧瓶中,加入月桂酸5g,红收集137-~138C的馏分即得溴十- ~烷3.5g。色氧化汞3.4g以及NBS,再加入四氯化碳100mL。2结中国煤化工搅拌,加热3h,冷却至室温,过滤,滤液用冰饱和食2.1投MHCNMHG收稿日期:2007-10-22试验了月桂酸和NBS的摩尔比(:1;1:1.1;1:1.2;作者简介:杨鑫骐(1979 >)男,浙江新昌人，硕士，从事农药合成和工艺1:1.3)对溴十一烷收率的影响,见表1。实验结果表研究。ZHEJIANG CHEMICAL INDUSTRYVol.39 No.03 (2008)明,NBS适当过量(1:1.2)有利于溴十- -烷收率的提3.2 结构表征高。可能是由于反应中NBS不溶于四氯化碳,非均'H-NMR:0.78-0.96ppm(t ,CH,3H,J=5H), 1.26-相反应的原因。1.37ppm(m,(CH)9,18H),3.49-3.54ppm(t,CH2Br,2H)表1投料比对收率的影响IR(cm^ ):2960, 1470, 1260。Table 1 The efects of molar ratio on the yield of 1-MS:m/e=234(M",1%), 165(BrC;Hr",10%),151bromoundecane(BrC;Hm~ ,10%),137( BrCH,100%), 127(-CgHg2%),投料比1:1.0 1:1.1 1:1.2 1:1.385(-CHIr,25%),57(-CH,73%)。澳十一烷收率/%535650614结论2.2温度对收率的影响以月桂酸和NBS为起始原料得到溴十- -烷,该试验了不同反应温度(25C，,40C,60C,80C)对工艺具有原料易得,反应条件温和等优点。经优化，溴十一烷收率的影响,见表2。实验结果表明,反应较佳工艺条件为:月桂酸和NBS的投料比为1:1.2,温度对反应收率影响不明显，考虑节能因素,采用反应温度为60,反应时间为3h。在上述工艺条件60C的反应温度。下,溴十- ~烷收率60%,含量98%,产品结构经IR、表2反应温度对收率的影响1HNMR和MS表征确认。Table 2 The efects of reaction temperature on the yield of参考文献:1-bromoundecane[1] Alkylbenzene Linear [ J ] Hydrocarbon Processing ,滴加温度/ C25_4(6(8C1997,76 (3):107-110.溴十一烷收率/%525860[2] John A Horsley. Producing Bulk and Fine Chemicals注:以1:1.2mol比投料Using Solid Acids [0]. Chemtech,1997,27 (10): 45-50.2.3反应时间对收率的影响[3]严赞开,张钟宁.美国白蛾性信息素的合成研究进展[试验了反应时间(1h,2h,3h, 4h)对溴十一烷收J]合成化学, 2003,11 ()11-18.率的影响,见表3.实验结果表明,3h后反应基本完[4]徐尚成瓢虫防卫生物碱2-(12-氨基十三烷基)吡咯烷的合成[J]农药学学报199, 1(1): 20-24.成。{5] Rodriguer, Sergio; Camps, Francisco; Fabrias, Gemma.表3反应时间对收率得影响Synthesis of gem-dideuterated tetradecanoic acids and their useTable 3 The efectst of reaction time on the yield ofin investigating the enzymatic transformnation of (2) -11 -lelradecenoic acid into (E,E)-10,12-letradecadienoic acid [].反应时间/ hJourmal of Organic Chemisty, 2001, 66(24) 8052- -8058.4[6] Bukovis G. J, Budzikiewicz H. Studies in chemical注:1:1.2mol比,60C反应温度ionization mass spectrometry. Part VI. The cleavage of a2.4重复性实验carbon-earbon double bond after chemical ionization with NO+以较佳工艺参照(月桂酸和NBS的投料比为1:- a cornplex rearrangement process [J] Organic Mass1.2,反应温度为60心,反应时间为3h)，进行三次重Spectrometry, 1984, 19(1): 23-26.复实验，重现性良好:收率60%+0.4%,相对标准偏差[7] Chorbadzhiev, S. Synhesis of medium and higherdialkyl disulfides [J] Revue Roumaine de Chimie, 1981, 26(RSD=0.67%。11-12):1447- -1450.3产品分析[8] Degueil -Castaing, Marie; Moutet, Laurent; Millard,3.1气相色谱分析Bemard.IntramolecularHomolytic Displacements.30.色谱条件(Chromatographic conditions):检测器:Functional Decarbonylative Transformations of Aldehydes viaFID;进样器:分流(分离比: 1:60);分离柱:30m毛细Homolotically Induced Decomposition of Unsaturated管柱,AT.SE- -30,内径:0.32mm,膜厚:0.33mm;柱温:-mistry, 200 65(3);:250心;气化室温度:270C;检测器温度:270C;载气3961-中国煤化工(N2)流速:40mL/min;氢气流速:30m/min;空气流速:MHC N M H Gproduction of alkylhalides [P]. FR:1039410, 1953-10-07.300mUmin。经面积归- -法分析,含量为98%。(下转第4页)-4-ZHEJLANG CHEMICAL INDUSTRYVol.39 No.03 (2008)1.2.3化合物5的合成2结论将29.1g化合物4 (0.15mol) 、2.5g 10% Pd/C、以D-苹果酸为手性源,经过酐活化、付-克反300mL冰醋酸投入500mL反应瓶进行常压加氢,室应、常压催化氢解和酯化四步反应合成了(R)-2-羟温高速搅拌48h。反应完全后抽滤回收Pd/C,滤液减基-4-苯基丁酸乙酯,总收率达到了68%。通过核磁压蒸除醋酸。所得浓缩液用80mL甲苯和300mL正和质谱分析,确证了目标产物的结构。己烷重结晶。产物烘干,得到25.9g白色晶体,收率参考文献: .96% , mp:119- 1219。[1] Herold P., Indolese A., et al. New technical aynthesis1.2.4 (R)-2-羟基- 4- 苯基丁酸乙酯1的合成of ehyl (R)- -2 -hydroxy- 4- phenylbutyrate of high enantiomeric将18.25g化合物5.160mL无水乙醇、6.5mL16%purity[J]. Tetrahedron, 200, 56: 6497-6499.的HCI无水乙醇溶液投入500mL烧瓶中,室温搅拌[2] Lin W, He z, et al. A practical syathesis of ethyl (R)反应24h。反应完全后加NaHCO3饱和溶液中和,减nd (S) -2 -hydroxy -4 -phenyl bulanoale and D压回收乙醇。然后加入500mL乙酸乙酯和200mLhomophenylalanine ethyI ester hydrochloride from L-malic acid饱和食盐水,萃取并洗涤,有机相用无水硫酸钠千[0 Tetahedron: Asymety, 200, 12: 1583-1587.[3] Chigusa Y,Yamanish M, Opical resolution of 2 -燥。常压蒸除溶剂后,再减压蒸馏,在40mmHg收集hydruxy 4- phenylbutanooic acid [P]. JP 2000136163, 2000.100~108C的馏分,得到无色液体20g,纯度99.7%[4] Kurauchi M, Matsueda H, Process for producing(HPLC),产率95% ,沸点212C/760mmHg。[a]22 =optically active 2-hydroxy -4-arylbutyric acid or its esler, and10° (c =neat);e.e. =99.2% (HPLC, OD -H, hexane/inlermediale therefor{P]. EP0759424, 1997.ethanol/TFA. 970/30 /0.4)。'H NMR (CDCI,400 MHz):[5] Matsuyama A, Kobayashi Y, Miorobial process for8(ppm)7.15-7.35 (m, 5H), 4.15- 4.25 (m, 3H), 2.70-2.90 preparing opically active 2-hyroxy-phenglbuyric acids(P].(m, 2H),3.61(1H), 2.05-2.20 (m, 1H), 1.90-2.00 (m，W08907147, 1989.1H), 1.30(t, 3H)。MS (EI,m/z): 208 (M+), 91 (100%)。New Technical Synthesis of Ethyl (R)-2-Hydroxy-4-phenylbutyrateYANG Wei-qiang , DAi Xi- xiang', LIN Xu _feng2(1.hijiang HISUN Pharmaceut Co.LTD, Taizhou, Zhejiang 318000 China;2.Department of Chemistry, ZhejiangUniversity, Hangzhou, Zhejiang 310027, China)Abstract:The synthetic methods on ethyI (R)- -2-hydroxy- 4- phenylbutyrate is described in detail. Using D-malic acid as materials, Ethyl (R)-2-hydroxy-4- phenylbutyrate is synthesized by four steps of anhydride activity,Frieded-Crafts reaction, hydrogenolysis and esterification.The product yield is 68%.The structure of the productwas determined by 'H NMR and MS.Keywords:ethyl (R)-2-hydroxy 4-phenylbutyrate; D malic acid; synthesis(上接第6页)Synthesis of 1-bromoundecaneYANG Xin-ji), SHEN De -long', Weng Jian -quan', CAI Qi-jun', JING Jian feng'(.College of Chemical Enginering and Materials Science, Zhejiang University of Technology, Hangzhou 310014,China ;2.Medicinal College of Jiaxin Universiy, Jiaxin31401, China)Abstract: With lauric acid and N -bromosuccinimide as starting materials, 1 -bromoundecane wassynthesized via Cristol ST reaction. The efets of the Treaction formula, reaction temperature and reaction time onthe yield of the product were studied. The optimized conditions中国煤化，工io of lauric acid toN -bromosucinimide was 1:1.2, the reaction temperature was:YHCNMHGUnder the aboveconditions, the yield of 1 -bromoundecane was 60%，the content was anove y%o. ine structure of 1 -bromoundecane was confirmed by IR, 'H NMR and MS.Keywords: lauric acid; N-bromosuccinimide; 1-bromoundecane ,Cristol ST reaction