2008年第39卷第3期《浙江化工》文章編號: 1006 4184(2008 )03 0005-02溴十-烷的合成楊鑫驥|2,沈德隆',翁建全',蔡啟軍,金劍鋒1(1.浙江工業(yè)大學化學工程與材料學院,浙江杭州310014;2浙江嘉興學院醫(yī)學院,浙江嘉興314001)摘要:以月桂酸和 N-溴代琥珀酰亞胺為起始原料經(jīng)Cristol sT反應(yīng)得到澳十一烷。考查了投料比、反應(yīng)溫度、反應(yīng)時間等實驗因素對產(chǎn)物收率的影響。經(jīng)過優(yōu)化，較佳的工藝條件為:月桂酸和N-溴代琥珀酰亞胺的摩爾比為1:1.2,反應(yīng)溫度609C, 反應(yīng)時間3h。溴十一烷收率為60%,含量98%。產(chǎn)品結(jié)構(gòu)經(jīng)IR、'H-NMR和MS表征確認。關(guān)鍵詞:月桂酸;N-溴代琥珀酰亞胺;溴十一烷;Cristol ST反應(yīng)溴代烴是有機合成中的重要中間體。澳十一烷,上改進采用月桂酸和N-溴代琥珀酰亞胺(NBS)作英文通用名:1-bromoundecane,無色液體，沸點為起始原料合成了溴十一烷,并對其工藝進行了優(yōu)137~138C( 18mmHg),廣泛應(yīng)用于直鏈芳烴及有機化,收率和液溴相比稍高。試劑等合成中1+。按起始原料分,其合成路線主要1實驗部分有以下幾條:1.十二醇和三溴化磷路線]:2.十二醛1.1主要儀器及試劑與一溴三氯甲烷路線;3.十二酸與溴路線;4十二Mercury Plus- 400型核磁共振儀,CDCl3作溶劑,酸乙酯與三溴化磷路線問。路線1和4收率比較低,TMS為內(nèi)標; Bruker Vector 22型紅外光譜儀,采用實驗條件要求比較高,路線2原料比較貴,需用到液膜法;HP5989B質(zhì)譜儀;GC900A型氣相色譜儀，的試劑多。路線3反應(yīng)條件溫和,收率高,但是反應(yīng)氫火焰檢測器。實驗中所用試劑皆為市購分析純。所用的溴化劑是液溴,有易揮發(fā)強腐蝕性和局部過1.2反應(yīng)過程濃導(dǎo)致副反應(yīng)多的缺點。本文作者在路線3的基礎(chǔ)反應(yīng)過程: .C.H2.COOH +N-Brcatalyzer 、C.jH2Br +N-H + CO21.3實驗過程鹽水洗,取有機層,用無水硫酸鈉千燥。過濾脫溶,在裝有恒壓滴液漏斗、溫度計、冷凝管和機械得淺黃 色(近乎無色)液體,減壓蒸餾(8毫米汞柱),攪拌的150mL四口圓底燒瓶中,加入月桂酸5g,紅收集137-~138C的餾分即得溴十- ~烷3.5g。色氧化汞3.4g以及NBS,再加入四氯化碳100mL。2結(jié)中國煤化工攪拌,加熱3h,冷卻至室溫,過濾,濾液用冰飽和食2.1投MHCNMHG收稿日期:2007-10-22試驗了月桂酸和NBS的摩爾比(:1;1:1.1;1:1.2;作者簡介:楊鑫騏(1979 >)男,浙江新昌人，碩士，從事農(nóng)藥合成和工藝1:1.3)對溴十一烷收率的影響,見表1。實驗結(jié)果表研究。ZHEJIANG CHEMICAL INDUSTRYVol.39 No.03 (2008)明,NBS適當過量(1:1.2)有利于溴十- -烷收率的提3.2 結(jié)構(gòu)表征高?？赡苁怯捎诜磻?yīng)中NBS不溶于四氯化碳,非均'H-NMR:0.78-0.96ppm(t ,CH,3H,J=5H), 1.26-相反應(yīng)的原因。1.37ppm(m,(CH)9,18H),3.49-3.54ppm(t,CH2Br,2H)表1投料比對收率的影響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結(jié)論2.2溫度對收率的影響以月桂酸和NBS為起始原料得到溴十- -烷,該試驗了不同反應(yīng)溫度(25C，,40C,60C,80C)對工藝具有原料易得,反應(yīng)條件溫和等優(yōu)點。經(jīng)優(yōu)化，溴十一烷收率的影響,見表2。實驗結(jié)果表明,反應(yīng)較佳工藝條件為:月桂酸和NBS的投料比為1:1.2,溫度對反應(yīng)收率影響不明顯，考慮節(jié)能因素,采用反應(yīng)溫度為60,反應(yīng)時間為3h。在上述工藝條件60C的反應(yīng)溫度。下,溴十- ~烷收率60%,含量98%,產(chǎn)品結(jié)構(gòu)經(jīng)IR、表2反應(yīng)溫度對收率的影響1HNMR和MS表征確認。Table 2 The efects of reaction temperature on the yield of參考文獻:1-bromoundecane[1] Alkylbenzene Linear [ J ] Hydrocarbon Processing ,滴加溫度/ 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反應(yīng)時間對收率的影響[3]嚴贊開,張鐘寧.美國白蛾性信息素的合成研究進展[試驗了反應(yīng)時間(1h,2h,3h, 4h)對溴十一烷收J]合成化學, 2003,11 ()11-18.率的影響,見表3.實驗結(jié)果表明,3h后反應(yīng)基本完[4]徐尚成瓢蟲防衛(wèi)生物堿2-(12-氨基十三烷基)吡咯烷的合成[J]農(nóng)藥學學報199, 1(1): 20-24.成。{5] Rodriguer, Sergio; Camps, Francisco; Fabrias, Gemma.表3反應(yīng)時間對收率得影響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 [].反應(yīng)時間/ 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反應(yīng)溫度ionization mass spectrometry. Part VI. The cleavage of a2.4重復(fù)性實驗carbon-earbon double bond after chemical ionization with NO+以較佳工藝參照(月桂酸和NBS的投料比為1:- a cornplex rearrangement process [J] Organic Mass1.2,反應(yīng)溫度為60心,反應(yīng)時間為3h)，進行三次重Spectrometry, 1984, 19(1): 23-26.復(fù)實驗，重現(xiàn)性良好:收率60%+0.4%,相對標準偏差[7] Chorbadzhiev, S. Synhesis of medium and higherdialkyl disulfides [J] Revue Roumaine de Chimie, 1981, 26(RSD=0.67%。11-12):1447- -1450.3產(chǎn)品分析[8] Degueil -Castaing, Marie; Moutet, Laurent; Millard,3.1氣相色譜分析Bemard.IntramolecularHomolytic Displacements.30.色譜條件(Chromatographic conditions):檢測器:Functional Decarbonylative Transformations of Aldehydes viaFID;進樣器:分流(分離比: 1:60);分離柱:30m毛細Homolotically Induced Decomposition of Unsaturated管柱,AT.SE- -30,內(nèi)徑:0.32mm,膜厚:0.33mm;柱溫:-mistry, 200 65(3);:250心;氣化室溫度:270C;檢測器溫度:270C;載氣3961-中國煤化工(N2)流速:40mL/min;氫氣流速:30m/min;空氣流速:MHC N M H Gproduction of alkylhalides [P]. FR:1039410, 1953-10-07.300mUmin。經(jīng)面積歸- -法分析,含量為98%。(下轉(zhuǎn)第4頁)-4-ZHEJLANG CHEMICAL INDUSTRYVol.39 No.03 (2008)1.2.3化合物5的合成2結(jié)論將29.1g化合物4 (0.15mol) 、2.5g 10% Pd/C、以D-蘋果酸為手性源,經(jīng)過酐活化、付-克反300mL冰醋酸投入500mL反應(yīng)瓶進行常壓加氫,室應(yīng)、常壓催化氫解和酯化四步反應(yīng)合成了(R)-2-羥溫高速攪拌48h。反應(yīng)完全后抽濾回收Pd/C,濾液減基-4-苯基丁酸乙酯,總收率達到了68%。通過核磁壓蒸除醋酸。所得濃縮液用80mL甲苯和300mL正和質(zhì)譜分析,確證了目標產(chǎn)物的結(jié)構(gòu)。己烷重結(jié)晶。產(chǎn)物烘干,得到25.9g白色晶體,收率參考文獻: .96% , mp:119- 1219。[1] Herold P., Indolese A., et al. New technical aynthesis1.2.4 (R)-2-羥基- 4- 苯基丁酸乙酯1的合成of ehyl (R)- -2 -hydroxy- 4- phenylbutyrate of high enantiomeric將18.25g化合物5.160mL無水乙醇、6.5mL16%purity[J]. Tetrahedron, 200, 56: 6497-6499.的HCI無水乙醇溶液投入500mL燒瓶中,室溫攪拌[2] Lin W, He z, et al. A practical syathesis of ethyl (R)反應(yīng)24h。反應(yīng)完全后加NaHCO3飽和溶液中和,減nd (S) -2 -hydroxy -4 -phenyl bulanoale and D壓回收乙醇。然后加入500mL乙酸乙酯和200mLhomophenylalanine ethyI ester hydrochloride from L-malic acid飽和食鹽水,萃取并洗滌,有機相用無水硫酸鈉千[0 Tetahedron: Asymety, 200, 12: 1583-1587.[3] Chigusa Y,Yamanish M, Opical resolution of 2 -燥。常壓蒸除溶劑后,再減壓蒸餾,在40mmHg收集hydruxy 4- phenylbutanooic acid [P]. JP 2000136163, 2000.100~108C的餾分,得到無色液體20g,純度99.7%[4] Kurauchi M, Matsueda H, Process for producing(HPLC),產(chǎn)率95% ,沸點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頁)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中國煤化，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