碘催化合成三乙基膦酰乙酸酯

1、第17卷第1期化學研究Vol .17No .12006年3月CHE M I CAL RESE ARCH Mar .2006 收稿日期:2005-09-23.基金項目:湖南省教育廳科研資助項目(02C050.作者簡介:蔡小華(1966-,男,副教授,博士,從事藥物化學教學與科研工作1E 2mail:caixh1111.碘催化合成三乙基膦酰乙酸酯蔡小華,劉志華,楊志學(懷化醫(yī)學高等專科學校藥學系,湖南懷化418000摘要:首次報道了碘對M ichael A rbuzov 重排反應的催化作用.以亞磷酸三乙酯與2-鹵代乙酸乙酯為原料,碘作催化劑,反應溫度80,反應時間2h,三乙基膦酰乙酸酯的產(chǎn)率達到9

2、0%-98%.關鍵詞:M ichael A rbuzov 重排反應;三乙基膦酰乙酸酯;亞磷酸三乙酯;碘;催化中圖分類號:O 627.5文獻標識碼:A 文章編號:1008-1011(200601-0041-03Synthesis of Tri ethyl Phosphonoacet ate Esters Cat alyzed by I odi n eCA I Xiao 2hua,L I U Zhi 2hua,Y ANG Zhi 2xue(D eparture of Phar m acology,Huaihua M edical College,Huaihua 418000,Hunan,China

3、 Abstract:It is reported firstly that i odine is a very good catalyst f or the M ichael A rbuz ov rearrange 2ment .Triethyl phos phonocetate esters were synthesized fr om triethyl phos phite and ethyl 22hal oacetateusing i odine as catalyst in 90%-98%yield under l ower te mperature and shorter react

4、i on ti m e .Keywords:M ichael A rbuz ov rearrange ment;triethyl phos phonocetate esters;triethyl phos phite;i o 2dine;catalysis三乙基膦酰乙酸酯是用途廣泛的有機磷合成試劑,也是合成藥物以及高強度和防水性能優(yōu)良的聚合材料中間體苯丙烯酸酯(如:32苯基2苯丙烯酸乙酯的重要原料1-3.三乙基膦酰乙酸酯主要是以亞磷酸三乙酯和22鹵代乙酸乙酯為原料,通過M ichael A rbuz ov 重排反應來合成的4,5.然而,該反應一般須在較高的溫度下,回流反應較長的時間.例如:合成

5、22乙氧基三乙基膦酰乙酸酯,需要在150下回流反應5h,而產(chǎn)率僅為83%6.作者發(fā)現(xiàn)碘對該反應具有很好的催化作用,不僅可以降低反應溫度,縮短反應時間,而且,產(chǎn)物產(chǎn)率也有較大的提高.在反應溫度為80和反應時間為2h 的條件下,以碘為催化劑合成三乙基膦酰乙酸酯(圖1,所有產(chǎn)物的產(chǎn)率均達到90%以上.因此,本合成方法對于合成在較高溫度條件不穩(wěn)定的膦酰乙酸酯特別有用.圖1碘催化合成三乙基膦酰乙酸酯Fig .1Synthesis of triethyl phos phonoacetate esters using i odine as catalyst42化學研究2006年1實驗部分1.1儀器與試劑I

6、R譜用Perkin El m er Spectrum one FT2I R s pectr ometer紅外光譜儀記錄;ESI2MS由Finnigan LCQ DECA質(zhì)譜儀記錄;1H NMR由Varian unity I nova2400核磁共振儀記錄(T MS為內(nèi)標;產(chǎn)物的純度用Perkin El m er Series 200高效液相色譜儀測定.原料1a2e自制,其它試劑均為國產(chǎn)C P級試劑.1.2實驗操作亞磷酸三乙酯(50mmol、22鹵代乙酸乙酯(1a2e,50mmol和碘(2.5mmol的混合液,在80下,加熱反應2h,反應完成后(T LC監(jiān)控,減壓蒸去低沸點物,得到淺黃色透明液體

7、三乙基膦酰乙酸酯(2a2e,該產(chǎn)物具有較好的純度,進一步純化,可以通過減壓蒸餾收集相應沸點的餾分.在壓力13.3Pa下,減壓蒸餾收集溫度為78-80、84-86、91-93、138-140、106-107的餾分,得到產(chǎn)物(2a2e均為無色油狀液體,產(chǎn)率分別為96%、97%、95%、92%、90%,產(chǎn)物的純度經(jīng)HP LC分析均在99%以上.1.3產(chǎn)物結構表征產(chǎn)物2a2e的化學結構經(jīng)I R、1H NMR和ESI2MS圖譜分析確證.2a:I Rmax(K B rc m-1:2982,2935,2910,1751,1479,1446,1392,1369,1323,1262,1164, 1118,102

8、7,975,888,857,794,742;ESI2MS:m/z=270(M+H+1+,10,269(M+H+,58, 267(M-H-,100;1H NMR(CDCl3:1.12(t,6H,J=7.2Hz,-OCH2CH3,1.17(t,3H,J= 7.2Hz,-OCH2CH3,1.25(t,3H,J=7.2Hz,-COOCH2CH3,3.34-3.55(m,2H,-O CH2CH3, 3.89(s,1H,-C H,4.06(q,4H,J=7.2Hz,-O CH2CH3,4.17(q,2H,J=7.2Hz,-COO CH2 CH3.2b:I Rmax(K B rc m-1:2980,2936

9、,2910,1739,1479,1446,1393,1367,1271,1164,1117, 1026,971,887,842,786;ESI2MS:m/z=247(M+Na+,100,225(M+H+,23,223(M-H-,15;1H NMR(CDCl3:1.13(t,6H,J=7.2Hz,-OCH2CH3,1.27(t,3H,J=7.2Hz,-COOCH2CH3,2.75(s,2H,-C H2,4.07(q,4H,J=7.2Hz,-O CH2CH3,4.15(q,2H,J=7.2 Hz,-COO CH2CH3.2c:I Rmax(K B rc m-1:2981,2935,2910,174

10、0,1476,1446,1393,1368,1270,1165,1110, 1026,975,892,845,757;ESI2MS:m/z=261(M+Na+,79,239(M+H+,100,237(M-H-,100;1H NMR(CDCl3:0.98(d,2H,J=7.2Hz,-C H3,1.12(t,6H,J=7.2Hz,-OCH2 CH3,1.28(t,3H,J=7.2Hz,-COOCH2CH3,2.59(q,1H,J=7.0Hz,-C H,4.06(q,4H,J= 7.2Hz,-O CH2CH3,4.15(q,2H,J=7.2Hz,-COO CH2CH3.2d:I Rmax(K B r

11、c m-1:2980,2934,2911,1732,1598,1503,1476,1446,1392,1367,1270, 1163,1110,1025,968,879,838,752;ESI2MS:m/z=301(M+H+,42,299(M-H-,100;1H NMR(CDCl3:1.12(t,6H,J=7.2Hz,-OCH2CH3,1.30(t,3H,J=7.2Hz,-COOCH2CH3,3.59(s,1H,-C H,4.07(q,4H,J=7.2Hz,-O CH2CH3,4.16(q,2H,J=7.2Hz,-COO CH2 CH3,7.06-7.09(m,3H,7.12(dd,3H,J=

12、8.0Hz,1.4Hz.2e:I Rmax(K B rc m-1:2981,2934,2901,1762,1480,1446,1366,1271,1159,1112,1020, 960,856,735;ESI2MS:m/z=309(M+Na+,100,287(M+H+,22,285(M-H-,100;1H NMR(CDCl3:1.13(t,6H,J=7.2Hz,-OCH2CH3,1.32(t,6H,J=7.2Hz,-COOCH2CH3,3.18 (s,1H,-CH,4.06(q,4H,J=7.2Hz,-O CH2CH3,4.14(q,4H,J=7.2Hz,-COO CH2CH3. 2結果與討論

13、2.1反應產(chǎn)率的影響因素作者選擇原料22氯222乙氧基乙酸乙酯(1a和亞磷酸三乙酯反應作為研究模板,對反應的條件進行了優(yōu)化.考慮到M ichael A rbuz ov重排反應的原料亞磷酸三乙酯和22鹵代乙酸乙酯一般采用等摩爾比,因此,作者第1期蔡小華等:碘催化合成三乙基膦酰乙酸酯43也采用等摩爾比的1a和亞磷酸三乙酯,考察了反應溫度、時間和催化劑的用量等因素對該反應的影響.結果如表1所示,顯然,該反應的較佳反應溫度、時間和催化劑與底物的摩爾比(x分別是80,2h和0.05.表1M ichael A rbuzov重排反應的影響因素Table1I nfluence fact ors ofM ich

14、ael A rbuzov rearrange ment catalyzed by i odineEntry/Yield a/%t/h Yield b/%x Yield c/%160721.5730.02587280962960.050963100962.5950.07595a時間t=2h,催化劑與底物摩爾比x=0.05;b溫度80,x=0.05;c時間2h,溫度802.2反應歷程M ichael A rbuz ov重排反應6是由于發(fā)生了兩次雙分子的親核取代反應,它的反應歷程如圖2所示. 圖2M ichael A rbuzov重排的歷程Fig.2Course of M ichael A rbuz

15、ov rearrangement碘催化該M ichael A rbuz ov重排反應,作者通過對反應過程取樣分析,得到了中間產(chǎn)物膦酰碘(圖譜分析證實,由于膦酰碘的活性較高,有利于產(chǎn)物的生成.該反應過程如圖3所示,在受熱的情況下,亞磷酸三乙酯迅速與碘反應生成活性更高的膦酰碘,膦酰碘再與鹵代乙酸乙酯縮合而得到目標產(chǎn)物,因此,可降低縮合反應溫度、縮短反應時間和提高反應產(chǎn)物的收率. 圖3碘催化M ichael A rbuzov重排的歷程Fig.3Course of M ichael A rbuzov rearrange ment catalyzed by i odine參考文獻:1Com ins D

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