合成化學(xué) Chinese Joumal of Synthetic Chemistry二481對(duì)羥基苯乙醇的合成繆震元,孫長(zhǎng)恩,華萬(wàn)森,陸路德南京理工大學(xué),江蘇南京210094)摘要:綜述了對(duì)羥基苯乙醇的重要合成方法及其最新進(jìn)展。參考文獻(xiàn)33篇關(guān)鍵詞:對(duì)羥基苯乙醇;合成;進(jìn)展;綜述中圖分類號(hào):TQ460文獻(xiàn)標(biāo)識(shí)碼:A文章編號(hào):1005-1511(2002)06-481-04The Synthesis of p-Hydroxy phenylethyl AlcoholMIAO Zhen-yuan, SUN Chang-en, HUA Wan-shen, LU Lu-de(Nanjing Uhiversity of Science and Technology, Nanjing 210094, China)Abstract: The main preparation methods of P-hydroxyphenylethyl alcohol have been described and thenew development of the methods is also introduced with 33 references.Key words: p hydroxyphenylethyl alcohol; synthesis; development; review1引言3酯還原法對(duì)羥基苯乙醇( p-hydroxyphenylethyl alcohol羧酸一般不易還原,但其酯相對(duì)而言較為容hydroxy benzenemethanol;; P tyrosol),分子式CH1o易還原,1996年李國(guó)青提出了一種用四氫鋁鋰O2,分子量138.1658,m.p.88℃~92℃,b.p.作還原劑的方法。反應(yīng)式如下:310C,極易溶于水、乙醇、乙醚、丙酮和醋酸。從氯仿中得到針狀晶體。天然存在于橄欖油、醬油、果OEtOEt灑和覆盆子中,是一種重要的醫(yī)藥和香料中間體。它能合成許多有用的藥物如:美多洛爾、倍他洛爾、紅景天甙等。現(xiàn)對(duì)其主要合成方法及其研究進(jìn)OH展作一簡(jiǎn)要綜述BzoHOr2發(fā)酵法Bz= Ph-CH早期的對(duì)羥基苯乙醇是通過(guò)細(xì)菌、酶、真菌等在發(fā)酵過(guò)程中產(chǎn)生的。例如精制甘蔗糖1200,水將對(duì)羥基苯乙酸乙酯溶入丙酮中,加入無(wú)水碳酸0L和L酪氨酸15g混合后加入酵母發(fā)酵,三四鉀和氯化芐,加熱回流20h,蒸去丙酮,用乙酸乙天發(fā)酵完成后除去酵母,濾液蒸發(fā)到糖漿狀時(shí),酯提取,然后用水洗,無(wú)水氯化鈣干燥,減壓濃縮先用醇提取羥苯基衍生物,然后用乙醚提取,再用得4苯甲氧基苯乙酸乙酯,然后在乙醚中用四氫氯仿提取得具有光澤的菱形針狀晶體,產(chǎn)率60%鋁鋰還原,接著催化氫化脫去苯甲基得對(duì)羥基苯80%乙醇。每步產(chǎn)率均在90%左右。中國(guó)煤化工收稿日期:2001-12-18作者筒介:震元(1974-),男,漢族,南京理工大學(xué)碩士。主娶從事CNMHG482合成化學(xué)vol.10,2002文獻(xiàn)-也分別提出了用四氫鋁鋰或硼氫化通過(guò)氧化酶或還原酶催化可以得到醛,但產(chǎn)鈉還原酯得到相應(yīng)的醇。 boesky(則提出了用固率不高酶的活性不好控制,不易工業(yè)化生產(chǎn):0;體氧化物CuO/ZrO作為催化劑催化氫化酯得到(3)臭氧氧化(R=CHCH=CH2,R2=OM)相應(yīng)的醇3-(4甲氧基苯基)丙烯溶于氯仿和甲醇的混合溶劑中,降溫至0C,通入含有5.6%臭氧的氧4以醛為中間體的合成法氣并攪拌至臭氡完全吸收,混合物立即蒸餾得產(chǎn)起始原料RCHR2生成醛后用還原劑(如物,產(chǎn)率約為37%NL:6 H2O)7n/DMF-H2O或o-6H102aH)5苯乙胺合成法還原為醇8,然后轉(zhuǎn)化成對(duì)羥基苯乙醇。按生成醛的途徑可分為三類:苯乙胺硝化后還原變成對(duì)氨基苯乙胺,然后(1)重排反應(yīng)制備醛(R2=OMe,C1)進(jìn)行重氮化、水解得到對(duì)羥基苯乙醇,但產(chǎn)率很對(duì)位上帶有R2基團(tuán)的氧化苯乙烯在HZSM低。如果硝化后先進(jìn)行重氮化和水解得到對(duì)硝基5沸石存在下以HC13為溶劑,N氣保護(hù),室溫條苯乙醇,接著還原成對(duì)胺基苯乙醇,再進(jìn)行重氮化件下反應(yīng)30mn,可得到相應(yīng)的醛。此法產(chǎn)率高、和水解得到對(duì)羥基苯乙醇,反應(yīng)分兩步進(jìn)行,產(chǎn)率選擇性好、條件溫和9可達(dá)到45%(12。反應(yīng)式如下(2)生物酶催化(R= CH CHNH2,zouisatlony2)hydroly sas HO1963年 Yamada應(yīng)用 White1方法合成了6苯乙醇合成法對(duì)羥基苯乙醇。他先使對(duì)羥基苯乙胺酰化,接著亞硝化酰胺得到N烷基N亞硝酰胺,熱消除N2得6,1以對(duì)氨基苯乙醇為中間產(chǎn)物到相應(yīng)的酯,最后水解生成對(duì)羥基苯乙醇。以β苯乙醇為原料的合成方法文獻(xiàn)報(bào)道較美國(guó)科學(xué)家則于192年提出了一種新穎多,大部分都采用先酯化、硝化、水解及催化氫化的路線,他們以對(duì)甲氧基苯乙胺為原料,經(jīng)過(guò)三步得p(4氮基苯基)乙醇,然后再經(jīng)過(guò)重氮化和水反應(yīng)生成對(duì)甲氧基苯乙醇,然后再通過(guò)官能團(tuán)轉(zhuǎn)解得到對(duì)羥基苯乙醇16-21化得到對(duì)羥基苯乙醇。反應(yīng)條件溫和,產(chǎn)率達(dá)到Henry1還提出了在硝基還原為氨基時(shí)采用90%以上。并且在此路線中提出了用羥基取代伯不同的催化劑,得到的產(chǎn)率不一樣采用氯化亞錫胺中的氮原子的一種簡(jiǎn)便方法。和鹽酸作為催化劑還原產(chǎn)率可達(dá)88%。AcohH中國(guó)煤化工CNMHG第6期繆震元等:對(duì)羥基苯乙醇的合成6.2以4-(2甲氧基乙基)苯酚為中間產(chǎn)物及重氮化和水解得到4(2甲氧乙基)苯酚然后黃嘉梓-25采用苯乙醇經(jīng)過(guò)氫氧化鈉和經(jīng)過(guò)官能團(tuán)轉(zhuǎn)化生成對(duì)羥基苯乙醇反應(yīng)式如下硫酸二甲酯生成苯乙甲醚,再經(jīng)過(guò)硝化、催化氫化oMezonatiOnOMeHO7對(duì)羥基苯甲酮法存在下氧化對(duì)羥基苯甲酮,得到二烷基乙縮醛衍生物,接著水解可得相應(yīng)的乙二醛衍生物,然后同Durrwachter等2在1993年提出了一種新時(shí)還原兩個(gè)羰基,得到對(duì)羥基苯乙醇反應(yīng)步驟簡(jiǎn)的合成方法,他們采用烷基亞硝酸鹽在酸和醇的單,具有一定的經(jīng)濟(jì)價(jià)值A(chǔ)RHHOr84溴苯酚合成法在碳酸鉀存在下4-溴苯酚與烯丙基溴在丙酮中回流,再經(jīng)過(guò)格氏反應(yīng)制備2-(4-烯丙氧基)苯乙張三奇等2在合成紅景天甙的過(guò)程中提出醇,然后在氯化鈀和氯化亞銅催化下通入氧氣,脫了以4-溴苯酚為原料,選擇烯丙基保護(hù)酚羥基。去烯丙基得到產(chǎn)物。BrtHCH=KC0329對(duì)硝甚氧化苯乙烯法種以苯酚為原料在Icws酸條件下合成對(duì)羥基苯乙醇的方法,也取得了很好的效果,產(chǎn)率都達(dá)到了此方法.用對(duì)硝基氧化苯乙烯在甲醇中95%左右。于4X10Pa氫氣壓力下用 Raney n催化氫化得對(duì)羥基苯乙醇作為一種重要的醫(yī)藥中間體,到對(duì)氨基苯乙醇,產(chǎn)率達(dá)到40%,然后按上面的隨著醫(yī)藥工業(yè)的發(fā)展需求量會(huì)越來(lái)越大,并且出重氮化得到對(duì)羥基苯乙醇。還有采用鋅和氯化鈣口看好,但國(guó)內(nèi)還沒(méi)有工業(yè)化生產(chǎn)。天津化工研究作為還原劑01的報(bào)道設(shè)計(jì)院正在開(kāi)發(fā)電解制備工藝,南京理工大學(xué)也準(zhǔn)備開(kāi)發(fā)新的工藝,使之能在國(guó)內(nèi)早日實(shí)現(xiàn)工業(yè)10結(jié)束語(yǔ)化生產(chǎn)最近,日本和俄羅斯的科學(xué)家-3提出了中國(guó)煤化工CNMHG合成化學(xué)Vol.10,2002參考文獻(xiàn)C3-amino-4-hydroxy Phenyl)-ethanol; 3-amino-tyrusol [J]. 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