30ZHEJIANG CHEMICAL INDUSTRYVol45No.7(2014)精細(xì)化工聚乙二醇400單油酸酯的研發(fā)及生產(chǎn)章城亮,王義永,盛曉園,丁婷婷,李祥清(浙江醫(yī)藥股份有限公司新昌制藥廠,浙江紹興312500摘要:以油酸、聚乙二醇400(PEG400)為原料,對(duì)甲苯磺酸為催化劑,酯化合成聚乙二醇400單油酸酯(PEG400M○)?？疾炝朔磻?yīng)溶劑、溫度、催化劑用量、溶劑用量、萃取用量等因素對(duì)酯化反應(yīng)的影響,最終確定最佳的反應(yīng)條件為油酸與PEG400的摩爾比為1:1.2,對(duì)甲苯磺酸投料量為油酸質(zhì)量的10%,環(huán)己烷投料量為油酸的10倍體積,在68℃加熱回流反應(yīng)約7h,反應(yīng)完全后加入與對(duì)甲苯磺酸等摩爾的碳酸氫鈉中和,再以油酸1.0倍質(zhì)量的PEG400分成等量3次萃取,萃取后減壓蒸餾除去環(huán)己烷,再經(jīng)過濾得到產(chǎn)品PEG400MO。以研發(fā)的工藝進(jìn)行工業(yè)化生產(chǎn),平均摩爾收率在90%左右,產(chǎn)品各項(xiàng)指標(biāo)符合標(biāo)準(zhǔn)要求。關(guān)鍵詞:聚乙二醇400單油酸酯;研發(fā);生產(chǎn)文章編號(hào):1006-4184(2014)7-0030-04聚乙二醇脂肪酸酯是一種非離子表面活性較快,所以本研究選擇對(duì)甲苯磺酸作催化劑叫。劑,具有高乳化性、增稠性、增溶性等特點(diǎn)。常用的有聚乙二醇油酸酯、聚乙二醇硬脂酸酯、聚乙1實(shí)驗(yàn)部分醇月桂酸酯等。其中聚乙二醇400單油酸酯1.1原料、試劑及設(shè)備(以下簡(jiǎn)稱PEG400MO)可作乳化劑、增溶劑、潤(rùn)滑油酸(溫州萬事達(dá)油脂,食品級(jí)),聚乙二醇劑、抗靜電劑等,在制藥、食品、紡織、日用化工工400(以下簡(jiǎn)稱PEG400,湖南爾康制藥有限公司業(yè)中應(yīng)用廣泛。醫(yī)藥級(jí)),對(duì)甲苯磺酸(蘇州虎丘區(qū)星火精細(xì)化工由于生產(chǎn)VE制品需要使用食品級(jí)乳化劑廠),正已烷(揚(yáng)子石化煉化有限公司),環(huán)已烷(韓PEGA00MO,要求PEG400MO顏色要淺,目前市場(chǎng)國(guó)IG),甲苯(韓國(guó)IG),碳酸氫鈉(湖南裕華化銷售的食品級(jí)PEGA400MO較少,且普遍存在外觀工集團(tuán)有限公司,食品級(jí)),旋轉(zhuǎn)蒸發(fā)儀(上海安亭顏色較深,無法滿足生產(chǎn)需求的問題。研發(fā)生產(chǎn)實(shí)驗(yàn)儀器有限公司)。食品級(jí)低色度乳化劑PEG400MO迫在眉睫。12實(shí)驗(yàn)原理常用的制備聚乙二醇脂肪酸酯的方法為油酸和PEG400在對(duì)甲苯磺酸催化下進(jìn)行酯步酯化法,聚乙二醇400和脂肪酸酯化反應(yīng)的催化反應(yīng),反應(yīng)生成PEG400MO,為避免聚乙二醇化劑有硫酸、對(duì)甲苯磺酸叫、硼酸吲、固體酸、脂肪400雙油酸酯的產(chǎn)生,一般PEG400投料過量。通酶等,由于硫酸價(jià)格低,工業(yè)生產(chǎn)PEG400MO,過考察反應(yīng)溶劑、反應(yīng)溫度等條件,分析所得產(chǎn)般以硫酸作為催化劑,但產(chǎn)物顏色較深。而對(duì)品的顏色等指標(biāo),選擇適合工業(yè)生產(chǎn)的工藝條甲苯磺酸價(jià)格合理,產(chǎn)品顏色好,催化反應(yīng)速度件。酯化反應(yīng)式如下收稿日期:2014-03-21作者簡(jiǎn)介:章城亮(1980-),男,浙江金華人,工程師,主要從事天然維生素E下游產(chǎn)品的研發(fā)及生產(chǎn)。2014年第45卷第7期浙化衛(wèi)對(duì)甲苯磺酸H￡CSO·HOR-COOH HO(CHCH,O)nHR-COO(CHCH,O)nH +H,O油酸聚乙二醇400聚乙二醇400單油酸酯13實(shí)驗(yàn)路線方法液測(cè)定酸值。對(duì)甲苯磺酸水合物分子量190,酸值將油酸和PEG400及溶劑加入帶有攪拌器、52.6ml/g;油酸分子量282,酸值35,4mI溫度計(jì)及分水器的四頸瓶中,加熱至回流溫度,再PEG400和溶劑酸值為0加入催化劑,反應(yīng)一段時(shí)間后,通過計(jì)算反應(yīng)液酸通過計(jì)算反應(yīng)液總酸值,減去對(duì)甲苯磺酸的值,確定酯化是否完全。總酸值,即為剩余未反應(yīng)的油酸總酸值,再除以油反應(yīng)結(jié)束后,加人碳酸氫鈉中和對(duì)甲苯磺酸,酸的酸值,即可得到剩余未反應(yīng)的油酸質(zhì)量。剩余然后升溫,減壓蒸餾除去溶劑。蒸畢,冷卻、過濾除質(zhì)量小于油酸投料量2.0%,即酯化轉(zhuǎn)化率大于去對(duì)甲苯磺酸鈉,最終得到產(chǎn)品。98.0%,視為酯化反應(yīng)完全。14反應(yīng)終點(diǎn)檢測(cè)方法計(jì)算公式如下反應(yīng)后取反應(yīng)液,用0.1molL氫氧化鈉滴定W剩余油酸質(zhì)量=(W總投料量xV反應(yīng)液酸值)-528×W對(duì)甲苯磺酸投料量35.41.5產(chǎn)品質(zhì)量指標(biāo)的建立由表2可知反應(yīng)溫度越高,反應(yīng)速度越快,但PEG400MO無國(guó)家及行業(yè)標(biāo)準(zhǔn),所以自行建產(chǎn)品的顏色越深,為了得到低色度的PEG400MO立了PEG400MO的產(chǎn)品質(zhì)量標(biāo)準(zhǔn),見表1。綜合反應(yīng)時(shí)間,首選環(huán)已烷作反應(yīng)溶劑表1PEG400MO質(zhì)量標(biāo)準(zhǔn)22催化劑的用量對(duì)反應(yīng)時(shí)間及產(chǎn)品顏色的影響油酸:PEG400的摩爾比為1:1.2,環(huán)已烷投料項(xiàng)目標(biāo)準(zhǔn)規(guī)定檢測(cè)方法量固定為油酸的10倍,考察對(duì)甲苯磺酸投料量對(duì)色度≤100鉑鉆色度單位( HAZEN)GB11903-1989酯化完全時(shí)間和產(chǎn)品顏色的影響,實(shí)驗(yàn)結(jié)果見表3。酸值≤5 mekongGB/T5530-2005皂化值75-95 mgKOH/gB/T5534-2008表3對(duì)甲苯磺酸用量對(duì)反應(yīng)時(shí)間及重金屬≤10mg/kgGB/T5009.74-2003產(chǎn)品顏色影響對(duì)甲苯磺酸用量酯化完全的時(shí)間h產(chǎn)品色度( HAZEN)油酸的5%2結(jié)果與討論油酸的7%油酸的10%2.1不同反應(yīng)溶劑及溫度對(duì)產(chǎn)品顏色的影響4276油酸的15%150油酸:PEG400的摩爾比為1:1.2,固定對(duì)甲苯油酸的20%磺酸為油酸質(zhì)量的5%,溶劑投料量固定為油酸的5倍。以正己烷、環(huán)已烷、甲苯作為反應(yīng)溶劑進(jìn)由表3可知,對(duì)甲苯磺酸投料量與反應(yīng)完全行實(shí)驗(yàn),實(shí)驗(yàn)結(jié)果見表2時(shí)間成反比,對(duì)甲苯磺酸投料量增加產(chǎn)品顏色加深,綜合反應(yīng)時(shí)間,為了降低成本,對(duì)甲苯磺酸的表2反應(yīng)溫度對(duì)產(chǎn)品顏色的影響投料量為油酸的10%較好。23溶劑的用量對(duì)反應(yīng)時(shí)間及產(chǎn)品顏色的影響反應(yīng)溶劑反應(yīng)溫度/℃酯化完全的產(chǎn)品色度時(shí)間/h(HAZEN油酸:PEG400的摩爾比為1:1.2,對(duì)甲苯磺酸正己烷投料量為油酸質(zhì)量的10%,以環(huán)己烷為反應(yīng)溶環(huán)已烷劑,考察環(huán)己烷投料量對(duì)酯化完全時(shí)間和產(chǎn)品顏ZHEJIANG CHEMICAL INDUSTRYVol45No.7(2014)表4環(huán)己烷用量對(duì)反應(yīng)時(shí)間及產(chǎn)品顏色影響取。萃取后減壓蒸餾除去環(huán)已烷,再經(jīng)過濾得到一環(huán)已烷投料量酯酷化完全的時(shí)間h產(chǎn)品色度( HAZEN產(chǎn)品PEG4010油酸的5倍體積油酸的7倍體積1503工業(yè)化生產(chǎn)油酸的10倍體積3.1生產(chǎn)裝備油酸的15倍體積14油酸的20倍體積18如圖1所示,按工藝要求配備的聚乙二醇400單油酸酯裝置流程圖。該裝備特點(diǎn)是配置簡(jiǎn)單,可由表4可知環(huán)己烷投料量與反應(yīng)完全時(shí)間在同一反應(yīng)釜內(nèi)完成反應(yīng)、萃取、蒸餾過程。成正比,環(huán)己烷投料量減少,產(chǎn)品顏色加深,綜合冷很題反應(yīng)時(shí)間、產(chǎn)品顏色考慮,環(huán)己烷投料量為油酸冷越水出的10倍體積較好。24萃取對(duì)產(chǎn)品顏色和收率的影響以環(huán)己烷為溶劑反應(yīng),由于PEG400過量20%,PEG400不溶于環(huán)已烷層,在反應(yīng)結(jié)束后靜溶劑份水置,會(huì)出現(xiàn)分層現(xiàn)象,上層顏色較淺為環(huán)己烷層溶解有PEG400MO,下層顏色較深為過量的戀汽tPEG400和有色雜質(zhì)。通過加入新的PEG400萃取,可以除去環(huán)己溶劑校增烷層中的有色雜質(zhì),以提高產(chǎn)品品質(zhì)。實(shí)驗(yàn)考察PEG400的萃取用量對(duì)產(chǎn)品顏色和收率影響。PEC400分成等量3次萃取,實(shí)驗(yàn)結(jié)果見表5圖1聚乙二醇400單油酸裝置流程圖表5聚乙二醇400萃取用量對(duì)產(chǎn)品顏色及收率影響32原料配比PPEG400用量產(chǎn)品顏色收率/%油酸:200kg;PEG400(反應(yīng)):340kg;對(duì)甲苯油酸0.5倍黃色磺酸:20kg;環(huán)已烷:2000L;碳酸氫鈉:9kg油酸08倍黃色PEG400(萃取):200kg。油酸10倍淡黃色33生產(chǎn)流程油酸1.2倍淡黃色油酸和PEG400投入反應(yīng)釜中,加熱至回流油酸1.5倍淡黃色溫度68℃,再加入催化劑,反應(yīng)約7h后,取樣檢由表5可知PEG400萃取量越大,產(chǎn)品顏色測(cè),加入碳酸氫鈉,再用PEG400萃取3次,再減越淺,收率越低,可能是PEG400層也會(huì)溶解部分壓蒸餾除去環(huán)己烷。蒸畢,冷卻、過濾,最終得到產(chǎn)品,所以萃取量增加,產(chǎn)品收率會(huì)降低。從成本產(chǎn)品?？紤],PEG400萃取量選擇為油酸的1.0倍,分成萃取后的PEG400可以套用到下批反應(yīng),不等量3次萃取。僅降低生產(chǎn)成本,還可以提高產(chǎn)品收率。2.5工藝參數(shù)路線確定34產(chǎn)品檢測(cè)結(jié)果經(jīng)實(shí)驗(yàn)確定生產(chǎn)條件參數(shù)如下按照建立的PEG400MO的產(chǎn)品質(zhì)量標(biāo)準(zhǔn)檢油酸:PEG400摩爾比1:1.2投料,對(duì)甲苯磺測(cè),生產(chǎn)得到的產(chǎn)品符合各項(xiàng)指標(biāo)要求。酸投料量為油酸質(zhì)量的10%,環(huán)己烷投料量為油酸的10倍體積,在68℃加熱回流反應(yīng)約7h,4結(jié)論應(yīng)完全后加對(duì)甲苯磺酸等摩爾的碳酸氫鈉中和采用自行研發(fā)的PEG400MO工藝,成功地應(yīng)2014年第45卷第7期浙化衛(wèi)Synthesis of Coumarin Derivatives Based on Tetramethy Cjuloidineas Raw materialWU Hua-biao, HAN Liang, ZU Xiao-yan, LI Yu-da, YE Qing, GAO Jian-rongZhejiang University of Technology, Hangzhou, Zhejiang 310014, ChinaAbstract: N, N-Bis (3-methyl -2-butene)-3-hydroxyanilin hydrobromide was prepared from m-aminophenol and 1-bromo-3-methyl-2-butene via nucleophilic substitution reaction at first. Then 8-hydroxy-1, 1, 7, 7-tetramethyljulolidine was synthesized by electrophilic substitution. And aldehyde group was intro-duced to prepare 9-formyl-8-hydroxy-1, 1, 7, 7-tetramethyljulolidine through Vilsmeir-Haack reaction. Reaction conditions for synthesis of N, N-bis(3-meyhyl-2-butene)-3-hydroxyanilin hydrobromide was explored,and the results showed that when the ratio of m-aminophenol and 1-bromo-3-methyl-2-butene was 1: 2 andcalcium carbonate was used as acid-binding agent, the yield was optimum. Then 9-formyl-8-hydroxy1, 1, 7, 7-tetramethyljulolidine reacted with 2-thiopheneacetonitrile or 4-bromophenylacetonitrile to preparetwo 3-arylcoumarin derivatives. The structure of the derivative and products were identified by H NMRspectroscopy. And the UV spectra of target products were testedKeywords: m-aminophenol; 1-bromo-3-methyl-2-butene; synthesis; tetramethyl julolidine; couvatives(上接第32頁(yè))用到工業(yè)化生產(chǎn)中,平均摩爾收率在90%左右,2]李行,陳水杰,巴紅亮,等硼酸酯法合成聚乙二醇(400產(chǎn)品各項(xiàng)指標(biāo)符合標(biāo)準(zhǔn)要求。單蓖麻油酸酯精細(xì)石油化工,2013,30(4):29-3「3]馮光瑛,楊仁春,魏天俊,等固體超強(qiáng)酸SO/nO2催化合成硬脂酸聚乙二醇400單酯的研究日用化學(xué)工業(yè)參考文獻(xiàn)1998(5):12-14]安紅,田志茗,宋偉明.混酸PEG酯的合成及性能硏究4]寇秀芬,徐家立,固定化脂肪酶催化聚乙二醇脂肪酸酯的J精細(xì)石油化工,1998(5):21-23.合成小生物工程學(xué)報(bào),1996(12):131-13The r& d and production of polyethylene glycol 400 monooleateZHANG Cheng-liang, WANG Yi-yong, SHENG Xiao-yuan, DING Ting-Ting, LI Xiang-Qing(Xinchang Pharmaceutical Factory, Zhejiang Medicine Co, Ltd, Shaoxing, Zhejiang 312500, China)Abstract: Polyethylene glycol 400 monooleate(PEG400MO) was prepared with oleic acid and polyethylene glycol 400(PEG400)as raw material, p-toluenesulfonic acid as a catalyst. The effects of reaction solventtemperature, amount of catalyst, the amount of solvent extraction amount on the esterification reaction were analyzed. The optimum reaction conditions were the oleic acid PEG400 molar ratio of 1: 1. 2, p-toluenesulfonicfeeding amount of 10% the mass oleic acid, cyclohexane feeding amount of 10 times the volume of oleic acidhe reaction was heated to reflux at 68C about 7 hours, after the reaction was completed, sodium bicarbonateequimolar with p-toluenesulfonic was added to neutralize, then 1.0 times oleic acid quality of (PEG400)wasdivided into 3 parts to extract, after extraction, the cyclohexane was removed by distillation under reduced pressure, then through filtrating to obtain the product PEG400MO. The process was applied to industrial production, the average yield was about 90 % the indicators of product conform to the standard requirementsKeywords: PEG400MO; research and development; production