CN103641788B - 一种手性2-羰基噁唑啉的合成方法 - Google Patents

一种手性2-羰基噁唑啉的合成方法 Download PDF

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CN103641788B
CN103641788B CN201310714096.3A CN201310714096A CN103641788B CN 103641788 B CN103641788 B CN 103641788B CN 201310714096 A CN201310714096 A CN 201310714096A CN 103641788 B CN103641788 B CN 103641788B
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chiral
carbonyl
oxazoline
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CN103641788A (zh
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罗梅
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Juancheng Second People's Hospital
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/18—Oxygen atoms
    • C07D263/20—Oxygen atoms attached in position 2
    • C07D263/22—Oxygen atoms attached in position 2 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to other ring carbon atoms

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  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

一种手性2-羰基噁唑啉，其化学式如下：

Description

一种手性2-羰基噁唑啉的合成方法
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2-羰基噁唑啉的合成方法。
二、背景技术
   手性2-羰基噁唑啉是重要的医药中间体，可用来合成抗癌药物【1-2】等,是国内外研究的热点之一，其合成方法有多种【3-4】。
参考文献：
1. Synthesis of 2-Oxazolidinones by Direct Condensation of 2-Aminoalcohols with Carbon Dioxide Using Chlorostannoxanes , Pulla, Sharon et al，ACS Sustainable Chemistry & Engineering, 1(3), 309-312; 2013.
2. Toward actinide molecular magnetic materials: voordination polymers of U(IV) and the organic acceptors TCNQ and TCNE ，Schelter, Eric J. et al，Inorganic Chemistry, 46(14), 5528-5536; 2007.
3. A method for manufacturing TCNQ, TCNQ derivatives, and their intermediates,Hanabusa, Akishizu et al
Jpn. Kokai Tokkyo Koho, 62253790, 05 Nov 1987.
4.Preparation of 7,7,8,8-tetracyanoquinodimethane and its derivatives ,Yamaguchi, Shunro and Hanafusa, Terukiyo, Chemistry Letters, (6), 689-90; 1985。
三、发明内容
    本发明旨在提供化合物手性化合物 (R)-4-苯基噁唑啉基-2-酮。所要解决的技术问题是一步合成得到目标产物。
    本合成方法包括合成和分离，所述的合成用50mol% 二水合氯化铜做催化剂，四氰乙烯10.0mmol，D-苯甘氨醇10.0g，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（1/1）洗脱，将收集的最后组分点自然挥发，得单晶(R)-4-苯基噁唑啉基-2-酮。
合成反应如下：
   本合成方法一步得到目标产物，工艺简单，操作方便。
   其反应机理可推测如下：
   四氰乙烯由于在空气及路易斯酸二水合氯化铜催化剂作用下不稳定，氰基首先生成甲酸，然后与过量的D-苯甘氨醇进行缩合反应，甲酸中的羟基与D-苯甘氨醇中的氨基，及羟基分别脱去两分子水，又与水分子作用，得手性化合物 (R)-4-苯基噁唑啉基-2-酮，其反应过程如下:
    
四、附图说明：
图1是(R)-4-苯基噁唑啉基-2-酮的X-衍射分析图。
五、具体实施方式
  在100mL两口瓶中,加入无水CuCl2·2H2O 0.70g (5 mmol), 50mL氯苯, 四氰乙烯1.32g (4.90mmol), D-苯甘氨醇 10.0 g, 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(1:1)柱层析,得无色油状液体, 产率65 %; [a]5 D= -30.78o (c = 0.0672, CH2Cl2)：1HNMR (500MHz, CDCl3, 27℃), δ (ppm) = 7.34～7.45 (m, 5H), 5.42 (s, 1H), 4.99 (t, J=0.5Hz, 1H), 4.78 (t, J=0.5Hz, 1H), 4.23 (t, J=0.5Hz, 1H), 13CNMR(125MHz, CDCl3, 27℃) 159.2, 139.1, 128.8, 128.5, 125.7, 72.2, 56.0; IR (KBr):3064, 3032, 2956, 2924, 2853, 1755, 1646, 1603, 1495, 1457, 1398, 1360, 1308, 1283, 1235, 1077, 1040, 960, 936, 924, 763, 700, 551, 492; HRMS: m/z (%): C9H9NO2, calcd for C9H9NO2 163.0633; found: 163.0638，该配合物的晶体数据如下：
配合物的晶体结构数据：
      经验式                C9 H9  N O2 
      分子量                163.17 
      温度                  173(2) K 
      波长                  0.71073 A 
      晶系， 空间群         正交晶系,  C2
      晶胞参数              a = 17.193(4) A   alpha = 90 deg. 
                            b = 5.7693(14) A    beta = 98.990 deg. 
                            c = 8.112 (2) A   gamma = 90 deg. 
      体积                  794.8（3）A^3 
      电荷密度              4,  1.364 Mg/m^3 
      吸收 校正参数         0.097 mm^-1 
      单胞内的电子数目      344 
      晶体大小               0.211 x 0.157 x 0.123 mm 
      Theta 角的范围         2.40 to 26.00 
      HKL的指标收集范围                 -20<=h<=20, -6<=k<7, -10<=l<=8 
      收集/独立衍射数据                 2771 / 1524 [R(int) = 0.0216] 
      theta = 30.5的数据完整度          99.4 %
      吸收校正的方法                    多层扫描
      最大最小的透过率                  0.7456 and 0.6491
      精修使用的方法                    F^2 的矩阵最小二乘法
      数据数目/使用限制的数目/参数数目  1524/1 / 13
      精修使用的方法                     1.099
      衍射点的一致性因子                 R1 = 0.0332，wR2= 0.0851
      可观察衍射的吻合因子               R1 = 0.0359, wR2 = 0.0872
       绝对构型参数                      1.3（13）
       差值傅里叶图上的最大峰顶和峰谷    0.200 and -0.147 e.A^-3
晶体典型的键长数据：
            N(1)-C(1)                     1.324(2) 
            N(1)-C(3)                     1.451(2) 
            N(1)-H(1)                     0.92(2) 
            O(1)-C(1)                     1.214(2) 
            O(2)-C(1)                     1.352(2) 
            O(2)-C(2)                     1.432(2) 
            C(2)-C(3)                     1.538(3) 
晶体典型的键角数据：
            C(1)-N(1)-C(3)              113.46(14) 
            C(1)-N(1)-H(1)              122.2(14) 
            C(3)-N(1)-H(1)              124.3(14) 
            C(1)-O(2)-C(2)              108.72(13) 
            O(1)-C(1)-N(1)              129.18(15) 
            O(1)-C(1)-O(2)              120.75(15) 
            N(1)-C(1)-O(2)              110.06(14) 
            O(2)-C(2)-C(3)              105.73(13) 

Claims (1)

1.一种结构式为的手性2-羰基噁唑啉的合成方法，包括合成和分离，其特征在于所述的合成用50mol％二水合氯化铜做催化剂，四氰乙烯10.0mmol，D-苯甘氨醇10.0g，用50mL氯苯做溶剂，回流反应3天后，柱层析分离，用石油醚/二氯甲烷按体积比1/1洗脱，将收集的最后组分点自然挥发，得单晶(R)-4-苯基噁唑啉基-2-酮。
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