CN102659706A - 一种手性噁唑啉的制备及合成方法 - Google Patents

一种手性噁唑啉的制备及合成方法 Download PDF

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CN102659706A
CN102659706A CN2012101166683A CN201210116668A CN102659706A CN 102659706 A CN102659706 A CN 102659706A CN 2012101166683 A CN2012101166683 A CN 2012101166683A CN 201210116668 A CN201210116668 A CN 201210116668A CN 102659706 A CN102659706 A CN 102659706A
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Abstract

一种手性噁唑啉的制备，其化学式如下：

Description

一种手性噁唑啉的制备及合成方法
  
一、技术领域
    本发明涉及一种新化合物及其制备方法，特别涉及一种手性化合物及其制备方法，        确切地说是一种手性噁唑啉的制备及合成方法。
二、背景技术 
   手性噁唑啉是重要的医药化工产品及催化剂，近年来，国内外最新报道了种类繁多的双齿，三齿及四齿噁唑啉对氢化反应、Heck 反应、烯丙基烷基化反应、Diels-Alder 反应，二乙基锌对醛的加成反应等具有非常好的催化活性。【1-13】
参考文献：
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  hydrogenation of olefins and imines,  Synlett,  2003, 833-836.
2. Tang, W. J.; Wang, W.M; Zhang, X. M. .  Phospholane–Oxazoline Ligands for Ir-Catalyzed    
  Asymmetric Hydrogenation, Angew . Chem., Int. Ed. Engl. 2003, 42, 943.
3. Hilgraf, R.; Pfaltz, A.  Chiral bis(N-tosylamino)phosphine- and TADDOL-phosphite-
  oxazolines as ligands in asymmetric catalysis Synlett.  1999, 1814-1816.
4. (a) Powell, M. T.; Hou, D.-R.; Perry, M. C.; Cui, X.; Burgess, K. Chiral Imidazolylidine
  Ligands for Asymmetric Hydrogenation of Aryl Alkenes, J. Am.Chem.Soc.2001, 123, 8878-8879. 
(b) Perry, M. C.; Cui, X.;Powell, M. T.; Hou, D.-R.; Reibenspies, J. H.; Burgess, K.  Optically    
 Active Iridium Imidazol-2-ylidene-oxazoline Complexes: Preparation and Use in Asymmetric    
 Hydrogenation of Arylalkenes, J. Am.Chem.  Soc.  2003, 125, 113-123.
5. Gilbertson, Scott. R.; Xie, D.J.; Fu, Z. , Proline derived phosphine–oxazoline ligands in the   
  asymmetric Heck reaction,  Tetrahedron Lett.  2001, 42, 365-368.
6. Hashimoto, Y.; Horie, Y.; Hayashi, M.; Saigo, K.  An efficient phosphorus-containing
  oxazoline ligand derived from cis-2-amino-3,3-dimethyl-1-indanol: application to the   
  palladium-catalyzed asymmetric Heck reaction   Tetrahedron:Asymmetry  2000, 11, 2205-
  2210.
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  asymmetric intermolecular Heck reaction with planar chiral diphosphine-oxazoline   
 ferrocenyl ligands Chem.Eur. J.  2003, 9, 3073-3081.
8. Gilbertson, S. R.; Xie, D . Proline-Based P, N Ligands in Palladium-Catalyzed Asymmetric 
 π-Allyl Addition,   Angew. Chem., Int. Ed. Engl.  1999, 38, 2750-2752.
9. Burgess, K.; Porte, A. M.  Application of novel phosphine oxazoline ligands in asymmetric       
 allylations of 4-acyloxy-2-pentene derivatives,  Tetrahedron: Asymmetry,  1998, 9, 2465-2469.
10. Bolm, C.; Xiao, L.; Kesselgruber, M.  Synthesis of novel chiral phosphinoCyrhetrenyl-
 oxazoline ligands and their application in asymmetric catalysis, Org. Biomol. Chem.  2003, 1, 145-152.
11. Watanabe, K.; Hirasawa, T.; Hiroi, K.  Lewis acid-catalyzed asymmetric diels-alder reactions   
 using chiral sulfoxide ligands: Chiral 2-(Arylsulfinylmethyl)-1,3-oxazoline derivatives, Chem. Pharm. Bull.  2002, 50, 372-379.
12. Wipf, P.; Wang, X.D.  A new ligand scaffold for catalytic asymmetric alkylzinc additions to 
 aldehydes , Org. Lett.  2002, 4, 1197-1200.
13. Schinnerl, M.; Seitz, M.; Kaiser, A.; Reiser, O.,  New applications of bis(oxazoline) ligands in   
 catalysis: Asymmetric 1,2-and 1,4-addition of ZnR2 to carbonyl compounds,  Org. Lett.  2001, 3, 4259-4262.
   申请人以7, 7, 8, 8-四氰基奎二甲烷与L-苯甘氨醇在105mol%氯化锌作催化剂下，得到了一种手性化合物 4-[4' (S)-苯基-4,5-二氢化-2-噁唑啉基]-苯乙腈。
一、发明内容 
    本发明旨在提供手性化合物4-[4' (S)-苯基-4,5-二氢化-2-噁唑啉基]-苯乙腈, 所要解决的技术问题是一步合成得到目标产物。
本发明所称的一种手性化合物是由7, 7, 8, 8-四氰基奎二甲烷与L-苯甘氨醇制备的由以下化学式所示的化合物： 
                         
Figure 2012101166683100002DEST_PATH_IMAGE002
                               （Ⅰ）                                          
  化学名称：4-[4' (S)-苯基-4,5-二氢化-2-噁唑啉基]-苯乙腈,简称化合物(I)。
  本合成方法包括合成和分离，所述的合成用105mol% 氯化锌做催化剂，7 ,7, 8, 8-四氰基奎二甲烷4.90mmol，L-苯甘氨醇 90mmol，用50mL氯苯做溶剂，回流反应3天后，柱层析分离，用石油醚/二氯甲烷（3/7）洗脱，将收集的最后组分点自然挥发，得单晶4-[4' (S)-苯基-4,5-二氢化-2-噁唑啉基]-苯乙腈。 
合成反应如下： 
Figure 2012101166683100002DEST_PATH_IMAGE004
   本合成方法一步得到目标产物，工艺简单，操作方便。该化合物在苯甲醛的腈硅化反应中显示了一定的催化效果，其转化率达48.8%。
   其反应机理可推测如下： 
   7, 7, 8, 8-四氰基奎二甲烷由于在空气及大量路易斯酸催化剂，大大过量的L-苯甘氨醇作用下不稳定，首先经过还原、分解生成了4-氰甲基苯腈，然后与大大过量的L-苯甘氨醇在氯化锌作用下得手性化合物4-[4' (S)-苯基-4,5-二氢化-2-噁唑啉基]-苯乙腈，其反应过程如下:
Figure 2012101166683100002DEST_PATH_IMAGE006
四、附图说明
图1是4-[4' (S)-苯基-4,5-二氢化-2-噁唑啉基]-苯乙腈的X-衍射分析图。
二、具体实施方式 
1. 4-[4' (S)-苯基-4,5-二氢化-2-噁唑啉基]-苯乙腈的制备
  在100mL两口瓶中,加入无水ZnCl2 70mg (0.74mmol), 50mL氯苯, 7, 7, 8, 8-四氰基奎二甲烷1.0g (4.90mmol), L-缬氨醇 9.3g, 将混合物在高温下回流72h,停止反应,减压以除去溶剂, ,将剩余物用水溶解,并用CH2Cl2(20mLx3)萃取,有机相用无水硫酸钠干燥,旋转除去溶剂,将粗产品用石油醚/ 二氯甲烷(3:7)柱层析,得无色油状液体, 产率42%; [a]5 D=-18.12o (c = 0.0552, CH2Cl2)：1HNMR (500MHz, CDCl3, 27℃), δ (ppm) = 8.07 (d, J=10Hz，1H), 7.26～7.42 (m，7H), 5.37～5.42 (m, 1H), 4.79～4.83 (m, 1H), 4.29 (t, J=Hz, 1H), 3.81(s, 2H); 13CNMR(125MHz, CDCl3, 27℃) 164.1, 142.1, 133.4, 129.3, 128.8, 127.8, 127.6, 126.8, 117.3, 75.0, 70.1, 23.7; IR (KBr):3061, 3030, 2947, 2854, 2249, 1723, 1648, 1614, 1579, 1514, 1494, 1475, 1455, 1416, 1356, 1334, 1318, 1302, 1277, 1252, 1179, 1181, 1113, 1073, 1021, 976, 950, 936, 923, 899, 824, 764, 752, 721, 699, 533, 483; HRMS: m/z (%): C17H14N2O, calcd for C17H14N2O 262.1106; found: 262.1105。
（三）、腈硅化反应应用 
 2-苯基-2-（三甲硅氧基）乙腈
0.1mmol 化合物I, 苯甲醛0.1mL, TMSCN 0.3 ml (3.3mmol), 2mL二氯甲烷 相继在20~30?C下加入，5天后， 加入水淬灭经柱层后（石油醚/二氯甲烷：5/1），得无色油状液体, 转化率率: 48.8 %；1H NMR (300MHz, CDCl3) 7.56–7.59 (m, 0.9 Hz, 2H), 7.31–7.34 (m, 3H), 5.43 (s, 1H), 0.16 (s, 9H). 13C NMR (75 MHz, CDCl3) 136.1, 128.8(x2), 126.2(x2), 119.1, 63.5, -0.39(x3).
            
Figure 2012101166683100002DEST_PATH_IMAGE008
。

Claims (3)

1.  一种手性噁唑啉的制备是由7, 7, 8, 8-四氰基奎二甲烷与L-苯甘氨醇制备的由以下化学式所示的化合物：
                                                                        
Figure 341854DEST_PATH_IMAGE002
                               （Ⅰ）。
2.   由权利要求1所述的化合物(I)的合成方法，包括合成和分离，其特征在于：所述的合成用105mol% 氯化锌做催化剂，7 ,7, 8, 8-四氰基奎二甲烷4.90mmol，L-苯甘氨醇 66mmol，用50mL氯苯做溶剂，回流反应3天后，柱层析分离，用石油醚/二氯甲烷（3/7）洗脱，将收集的最后组分点自然挥发，得单晶4-[4' (S)-苯基-4,5-二氢化-2-噁唑啉基]-苯乙腈。
3.  该化合物在苯甲醛的腈硅化反应中显示了一定的催化效果，其转化率达48.8%。
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CN102659707A (zh) * 2012-04-26 2012-09-12 罗梅 一种手性化合物的制备及用途
CN103044346A (zh) * 2013-01-12 2013-04-17 罗梅 一种手性噁唑啉及其合成方法

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CN102229604A (zh) * 2011-04-22 2011-11-02 罗梅 一种手性噁唑啉的制备及合成方法
CN102382138A (zh) * 2011-07-28 2012-03-21 罗梅 一种手性双膦酰二胺化合物及用途
CN102643246A (zh) * 2012-03-22 2012-08-22 罗梅 一种手性2-羰基噁唑啉的合成方法
CN102659633A (zh) * 2012-04-12 2012-09-12 罗梅 一种手性酰铵盐的合成方法
CN102659707A (zh) * 2012-04-26 2012-09-12 罗梅 一种手性化合物的制备及用途

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CN102225915A (zh) * 2011-05-16 2011-10-26 罗梅 一种手性噁唑啉及其合成方法
CN102382138A (zh) * 2011-07-28 2012-03-21 罗梅 一种手性双膦酰二胺化合物及用途
CN102643246A (zh) * 2012-03-22 2012-08-22 罗梅 一种手性2-羰基噁唑啉的合成方法
CN102659633A (zh) * 2012-04-12 2012-09-12 罗梅 一种手性酰铵盐的合成方法
CN102659707A (zh) * 2012-04-26 2012-09-12 罗梅 一种手性化合物的制备及用途

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102659707A (zh) * 2012-04-26 2012-09-12 罗梅 一种手性化合物的制备及用途
CN102659707B (zh) * 2012-04-26 2014-10-08 罗梅 一种手性化合物的制备及用途
CN103044346A (zh) * 2013-01-12 2013-04-17 罗梅 一种手性噁唑啉及其合成方法

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