第35卷第6武漢工程大學(xué)學(xué)報(bào)Vol 35 No 62013年06月. Wuhan Inst. Tech.Jun.2013文章編號(hào):1674-2869(2013)06-0016-04β亞甲基苯乙醇的合成工藝奚強(qiáng),馮薇偉,胡楊3,余利民2,陳建2(1.武漢工程大學(xué)化工與制藥學(xué)院,湖北武漢430074;2.武漢理工大學(xué)化學(xué)工程學(xué)院,湖北武漢430070)摘要:針對(duì)β亞甲基苯乙醇合成工藝中反應(yīng)條件較苛刻、操作較復(fù)雜、產(chǎn)物難分離純化和總收率偏低的問(wèn)題,以苯乙醛為原料,經(jīng)亞甲基化反應(yīng)和均相氫轉(zhuǎn)移還原反應(yīng)兩步合成了β亞甲基苯乙醇分別考察了兩步反應(yīng)投料比、催化劑的用量和反應(yīng)溫度等條件對(duì)產(chǎn)物收率的影響結(jié)果表明,亞甲基化反應(yīng)在50℃,投料比為苯乙醛):n(甲醛):n(二甲胺鹽酸鹽)=1:1.2:0.2的條件下反應(yīng)16h最佳,反應(yīng)液經(jīng)減壓蒸出甲醛、異內(nèi)醇和水,中間產(chǎn)物無(wú)需進(jìn)一步純化,直接用于還原反應(yīng);氫轉(zhuǎn)移還原反應(yīng)于60~65℃下反應(yīng)12h,投料比n(a亞甲基苯乙醛):n(異丙醇鋁)=1:0.1,反應(yīng)液用乙酸乙酯和水萃取、純化,得到β亞甲基苯乙醇.產(chǎn)物的總收率可達(dá)86%,純度98.5%以上,其結(jié)構(gòu)經(jīng)核磁共振氫譜確認(rèn).該合成工藝反應(yīng)條件溫和、操作簡(jiǎn)單、產(chǎn)物易于分離和純化、收率高,具有一定的工業(yè)化價(jià)值關(guān)鍵詞:苯乙醛;亞甲基化;氫轉(zhuǎn)移還原中圖分類號(hào):TQ243.4文獻(xiàn)標(biāo)識(shí)碼:Adoi:10.3969/ 1. Issn.1674-2869.2013.06.0040引言1實(shí)驗(yàn)部分B亞甲基苯乙醇( methylene phenethyl1.1儀器及試劑alcohol),為一種透明的無(wú)色液體,具有柔和的玫DF-101S集熱式恒溫加熱磁力攪拌器,鞏義瑰香味,現(xiàn)多作為一種新型的香料,也可作為合成市予華儀器有限公司生產(chǎn);2XZ型雙級(jí)旋片式真其它香料的原料,是精細(xì)化工方面一種重要的空泵,鞏義市予華儀器有限公司生產(chǎn);二乙胺、丙中間體酸、四氫吡咯、吡啶、二甲胺鹽酸鹽、苯乙醛、甲醛現(xiàn)有的亞甲基苯乙醇的合成方法主要有三水溶液、異丙醇鋁、異丙醇、乙酸乙酯,均為國(guó)藥集種,方法一:通過(guò)格氏試劑的方法,該方法中的格團(tuán)化學(xué)試劑有限公司生產(chǎn)氏試劑較難制備2).方法二:利用Heck反應(yīng),用鹵1.2a亞甲基苯乙醛的合成代苯和烯丙醇發(fā)生偶合反應(yīng)制備,反應(yīng)中使用了在N2保護(hù)下,在500mL的三口燒瓶中,加入貴金屬鈀為催化劑,回收使用不易3,方法三:用240mL的異丙醇,攪拌下加入1.8g阻聚劑和甲基苯乙烯為原料,經(jīng)氯代、酯化和皂化反應(yīng)制60g(0.5mol)苯乙醛,攪拌均勻,滴加8.1g得,該路線較長(zhǎng),收率偏低43(0.1mol)二甲胺鹽酸鹽溶于48g質(zhì)量分?jǐn)?shù)37%本實(shí)驗(yàn)參考相關(guān)文獻(xiàn)67,以苯乙醛為原料,的甲醛水溶液(0.6mo)的混合溶液,控制滴加的經(jīng)亞甲基化和氫轉(zhuǎn)移還原兩步合成了亞甲基苯速率,使內(nèi)溫不超過(guò)50℃,滴加完畢后50C保溫乙醇,并探討了投料比催化劑的用量和反應(yīng)溫度反應(yīng),TIC跟蹤反應(yīng)至苯乙醛反應(yīng)完全反應(yīng)液常等條件對(duì)收率的影響.在最佳反應(yīng)條件下,以苯乙溫減壓蒸出過(guò)量的甲醛,50℃減壓蒸出溶劑和生醛計(jì),產(chǎn)物亞甲基苯乙醇的收率可達(dá)86%.同時(shí)成的水,并用異丙醇(20mL)帶兩次水,得一淺黃用HNMR對(duì)產(chǎn)物進(jìn)行了表征合成的路線如下:色粘稠物,即為a亞甲基苯乙醛粗品,不經(jīng)純化,亞甲基化oH直接用于氫轉(zhuǎn)移還原反應(yīng)CHOCHOV凵中國(guó)煤化工CNMHG收稿日期:2013-04-03作者簡(jiǎn)介:奚強(qiáng)(1966-),男,湖北浠水人,教授,博士,碩士研究生導(dǎo)師研究方向:有機(jī)合成第6期奚強(qiáng),等:P亞甲基苯乙醇的合成工藝171.3β亞甲基苯乙醇的合成往上述粘稠物中加入120g(2mol)異丙醇,升溫?cái)嚢枞芮?補(bǔ)加適量阻聚劑后,再加入10.2g(0.05mol)異丙醇鋁,升溫至60~65℃反應(yīng)TLC跟蹤反應(yīng)至醛反應(yīng)完全.反應(yīng)液減壓蒸出生成的丙酮和過(guò)量的異丙醇后,攪拌下趁熱將反應(yīng)80液傾倒人300mL的蒸餾水中,用300mL的乙酸反應(yīng)溫度/℃C乙酯分三次萃取,合并有機(jī)相,水洗,無(wú)水硫酸鈉圖1亞甲基化反應(yīng)溫度對(duì)反應(yīng)時(shí)間和亞甲基化干燥,過(guò)濾濾液減壓蒸出乙酸乙酯,得一淡黃色收率的影響透明的油狀物57.5g,即為β亞甲基苯乙醇,總收Fig. 1 The effect of temperature on reaction time率86%,純度98.5%(HPLC).and yield of product2結(jié)果與討論能是溫度較高時(shí)導(dǎo)致a亞甲基苯乙醛的聚合過(guò)度.由此可見(jiàn),此處亞甲基化反應(yīng)的溫度在50℃2.1亞甲基化反應(yīng)催化劑的選擇左右為佳根據(jù)文獻(xiàn)[6],本研究對(duì)亞甲基化反應(yīng)的催化2.3甲醛和苯乙醛的摩爾比對(duì)亞甲基化收率的劑做了初步篩選,其催化機(jī)理可認(rèn)為8:在堿催化影響下,苯乙醛在醛基的a位生成碳負(fù)離子,再與甲醛在50C,催化劑和苯乙醛摩爾比0.2:1,考中的羰基碳原子發(fā)生親核加成反應(yīng)生成2羥甲基察了原料甲醛和苯乙醛的摩爾比對(duì)收率的影響,苯乙醛;后者在酸催化下,受熱脫水,生成a亞甲結(jié)果如圖2所示.由圖可知,隨著甲醛和苯乙醛摩基苯乙醛.爾比的增大,反應(yīng)的收率有一定程度的提高,當(dāng)摩以甲醛和苯乙醛摩爾比1.2:1,反應(yīng)溫度為爾比高于1.2后,收率變化不明顯.考慮到過(guò)多的50℃,催化劑和苯乙醛摩爾比0.2:1,考察不同甲醛對(duì)后處理造成的麻煩,最后確定原料的摩爾的催化劑催化反應(yīng)的時(shí)間和亞甲基化收率,結(jié)果比為1.2:1見(jiàn)表1.由表可知,不同的催化劑對(duì)反應(yīng)時(shí)間和亞甲基化收率有較為顯著的影響,其中二甲胺鹽酸鹽催化時(shí)反應(yīng)時(shí)間最短,收率最高表1催化劑對(duì)亞甲基化反應(yīng)收率的影響Table 1 Effect of catalyst on yield of product催化劑反應(yīng)時(shí)間/h收率’/%1.3甲胺鹽酸鹽16n(甲醛):n(苯乙醛)乙胺鹽酸鹽圖2甲醛和苯乙醛的摩爾比對(duì)亞甲基化收率的影響乙胺丙酸鹽Fig. 2 Effect of proportion on yield of product4四氫吡咯丙酸鹽2.4氫轉(zhuǎn)移還原的反應(yīng)溫度對(duì)反應(yīng)時(shí)間和還原吡啶鹽酸鹽收率的影響注:“為柱色譜得到收率,下同;““為80℃時(shí)反應(yīng)根據(jù)文獻(xiàn)[7],在異丙醇鋁和a亞甲基苯乙醛48h,TLC顯示未反應(yīng)完摩爾比為0.1:1的條件下,對(duì)異丙醇和異丙醇鋁2.2亞甲基化的反應(yīng)溫度對(duì)反應(yīng)時(shí)間和亞甲基催化的氫轉(zhuǎn)移還原反應(yīng)的溫度對(duì)反應(yīng)時(shí)間和還原化收率的影響收率的影響進(jìn)行了初步研究,其結(jié)果見(jiàn)圖3所示以甲醛和苯乙醛摩爾比1.2:1,催化劑和苯隨著還原反應(yīng)溫度的升高,反應(yīng)速率逐漸增加,但乙醛摩爾比0.2:1,考察了不同的反應(yīng)溫度對(duì)反從70℃增加至反應(yīng)液回流溫度,反應(yīng)時(shí)間沒(méi)有明應(yīng)時(shí)間和亞甲基化收率的影響,結(jié)果見(jiàn)圖顯的變短.另一方面,在65℃過(guò)后,溫度的提高,由圖1可知,隨著反應(yīng)溫度的升高,反應(yīng)速率還原收率卻略有下降考慮到中間產(chǎn)物a亞甲基變大,反應(yīng)時(shí)間逐漸變短在溫度60℃之前,溫度苯乙醛易聚中國(guó)煤化工溫度控制在的升高對(duì)收率影響不大;但是繼續(xù)升高反應(yīng)溫度,60~65℃HCNMHG收率則出現(xiàn)較大的下降,從柱色譜的結(jié)果分析,可18武漢工程大學(xué)學(xué)報(bào)第35卷100應(yīng)時(shí)間和溫度的關(guān)系原收率和溫度的關(guān)系反應(yīng)溫度/C圖3氫轉(zhuǎn)移還原的反應(yīng)溫度對(duì)反應(yīng)時(shí)間和還原收率的影響Fig 3 The effect of temperature on reaction time§8至2.5異丙醇鋁和a亞甲基苯乙醛的摩爾比對(duì)還圖5P亞甲基苯乙醇的HNMR圖譜原收率的影響Fig 5H NMR spectra of A-methylene在溫度60~65℃C,考察了還原反應(yīng)異丙醇鋁phenethyl alcohol結(jié)果如圖4所示,由圖4可知,隨著催化劑和底物3結(jié)語(yǔ)摩爾比的提高,還原收率有一個(gè)最大值,即在摩爾本實(shí)驗(yàn)以苯乙醛為原料,經(jīng)亞甲基化和氫轉(zhuǎn)比0.1~0.12之間,收率最高可達(dá)92%.在較低的移還原兩步合成了β亞甲基苯乙醇.并確定了最催化劑量的條件下,反應(yīng)的時(shí)間有所延長(zhǎng),TLC顯佳反應(yīng)條件:亞甲基化反應(yīng)的苯乙醛:甲醛:二示聚合物的量有所增多,導(dǎo)致收率變低;另一方甲胺鹽酸鹽摩爾比為1:1.2:0.2,其反應(yīng)溫度面,在較高的催化劑量的條件下,還原的反應(yīng)速率50℃;氫轉(zhuǎn)移還原的中間產(chǎn)物:異丙醇鋁摩爾比很快,但是還原反應(yīng)結(jié)束后,水處理的過(guò)程中會(huì)產(chǎn)為1:0.1,反應(yīng)溫度60~65℃.以苯乙醛計(jì),產(chǎn)物生大量的鋁鹽,直接影響了產(chǎn)物的分離和純化,間亞甲基苯乙醇的總收率可達(dá)86%,該合成方法,接的導(dǎo)致收率明顯的下降綜合考慮,本實(shí)驗(yàn)確定工藝簡(jiǎn)單產(chǎn)物易于分離和純化收率高,具有最佳的摩爾比為0.1定的工業(yè)化價(jià)值致謝本研究得到了武漢同道興建材科技股份有限公司的盧洪宇工程師和武漢大學(xué)王慶利博士的幫助,在此一并表示感謝.0.080.120.16n(異丙醇鋁)n(a-亞甲基苯乙醛)參考文獻(xiàn):圖4異丙醇鋁和a亞甲基苯乙醛靡爾比對(duì)還原[1]郭廷翹,劉麗琴郭雪飛.用a甲基苯乙烯合成龍葵收率的影響醇系列香料[J.精細(xì)化工,2001,18(1):34-36Fig. 4 Effect of proportion on yield of productGuo Ting-qiao, LIU Li-qin, GUo Xue-fei.2.6產(chǎn)物亞甲基苯乙醇的表征Synthesis of hydratropic alcohol series flavors from產(chǎn)物的HNMR(CDCl3,TMS,300MHz)圖methylstyrene[J]. Fine Chemicals, 2001, 18(1):34譜如圖5所示:8180(s,1H)為羥基活潑氫;84.5536. (in chinese)(s,2H)為與羥基相連的亞甲基的氫:5.36~5.48[2] Behenna, Douglas C. Enantioselective decarboxylative(d,2H)為端烯的兩個(gè)氫;87.08~7.47(m,5H)為alkylations: catalyst development, substrate cope苯環(huán)上的氫的多重峰.與原料苯乙醛的核磁相比and mechanistic studies[J]. Chemistry-A EuropeanJournal,2011,17(50):14199-14223較,產(chǎn)物的核磁中出現(xiàn)了85.36~5.48端烯氫的[3] Mo Jur, Ruan jiwu, Liu shi-fang,etal. Regiosele-峰,并且原料中醛基氫的峰消失.由圖譜可知,制ctive h備的產(chǎn)物即為目標(biāo)產(chǎn)物B亞甲基苯乙醇V凵中國(guó)煤化工ahopcatalyscation, 2CNMHGry Comme第6期奚強(qiáng),等:}亞甲基苯乙醇的合成工藝[4] Mark A S, Robert P B. Beta-alky-lidene phenethyl世界,2008,49(1):42-45alcohols, organoleptic uses thereof and processes forLUO Ge, LIU Xin-wen, XU Ning, et al. Studiespreparing same: US, 4756840LP]. 1988-07-1activation and recycle of aluminium isopropoxide in[5]劉麗琴郭廷翹,左宏,等,玫瑰型香料亞甲基苯乙the homogeneous hydrogen transfer reaction of醇的合成[門].精細(xì)化工,2000,17(5):258-259.acrolein to allyl alcohol[J]. Chemical World, 2008LIU Li-qin, GUO Ting-qiao, ZUO Hong, et al.49(1):42-45.( in chinese)Synthesis of A-methylene phenethyl alcohol[J].Fine[8]唐培堃馮亞青.精細(xì)有機(jī)合成化學(xué)與工藝學(xué)[M.2Chemicals, 2000, 17(5):258-259. (in chinese)版.北京:化學(xué)工業(yè)出版社,2006:324-325[6] Erkkilae A, Pinko P M. Mild organocatalytic arTANG Pei-kun, FENG Ya-qing. Synthetic Organicmethylenation of aldehydes[J]. Journal of OrganicChemistry and Technology of Fine Chemicals[M].Chemistry,2006,71(6):2538-25412nd edition. Beijing: Chemical Industry Press, 2006[7]羅鴿,劉歆文,許寧等丙烯醛與異丙醇均相氫轉(zhuǎn)移324-325. (in chinese)制烯丙醇反應(yīng)中催化劑失活及再利用研究[J].化學(xué)Synthesis of A-methylene phenethyl alcoholXI Qiang, FENG Wei-wei, HU Yang, YU Li-ming, CHEN Jia(1. School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430074, China;2. Chemical Engineering Institute, Wuhan University of Technology, Wuhan 430070, China)Abstract: To improve the yield of the P-methylene phenethyl alcohol and avoid the disadvantagesluding harsh conditions, hard to control the reaction process, difficult purification and low yield inthe present routes, an approach to synthesize A-methylene phenethyl alcohol was investigated witlphenylacetaldehyde as the raw material by methylenation and hydrogen transfer reaction. The effects ofmolar ratio of material, amount of catalyst and reaction temperature on the yield of the product werediscussed. the yield of A-methylene phenethyl alcohol reached 86% with purity of over 98. 5%when themethylenation was carried out at 50 C for 16 h and ratio of n( phenylacetaldehyde):n(formaldehyde)n(organic amine salt)=1: 1.2: 0.2, formaldehyde, isopropanol and water were distilled from thereaction liquid by vacuum evaporation and the intermediate product was directly used without furtherpurification the hydrogen transfer reaction was carried out at 60-65 C for 12 h with n(intermediate):n(aluminum isopropoxide)=1: 0.1, the concentrate was extracted by ethyl acetate and water. Thestructure of the product was confirmed by IH NMR. This process has the characteristics of mildreaction conditions, simple operation, easy to be isolated and purified high total yield, which isKey words: phenylacetaldehyde; methylenation; hydrogen transfer reaction本文編輯:張瑞中國(guó)煤化工CNMHG