室温下碘催化一锅合成4-噻唑啉酮类化合物

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(淮阴师范学院 化学化工学院,江苏 淮安 223300)

0 引言

近年来,杂环化合物显示出越来越重要的作用,其中4-噻唑啉酮类杂环化合物在农药和医药领域都表现出较好的生物活性,如:杀菌[1,2]、杀虫[3]、除草[4]、抗HIV[5,6]、抗癌[7]、抗黄热病病毒[8]等活性．合成4-噻唑啉酮类化合物的传统方法是:席夫碱和巯基乙酸反应[9],或醛、胺和巯基乙酸反应,用苯作溶剂,回流10～12h[10];以四氢呋喃(tetrahydrofuran,THF)为溶剂,N,N′-二环己基碳化二亚胺(dicyclohexylcarbodiimide,DCC)作为脱水剂,室温下一锅反应合环[11];也有通过苯作溶剂微波辐射合成4-噻唑啉酮类化合物[12]．显然,这些方法反应时间长,且使用有毒的溶剂或催化剂．

自从Cromwell等[13]把I2用于催化合成氮杂环丙烷以来,I2作为催化剂在有机合成中的重要作用,已引起人们的极大关注．I2除被用作氧化剂外[14,15],研究表明,它作为一种催化剂具有易得、高效、操作简单等优点,因此已被广泛用于有机合成,具有很好的应用前景．本文报道在室温下,以冰醋酸为介质,碘单质为催化剂,使醛、胺与巯基乙酸发生缩合反应,生成4-噻唑啉酮类化合物(图1),与传统方法比该法具有反应时间短、操作简便和环境友好等优点．所得化合物的结构均经元素分析和1H NMR确证,采用X射线单晶衍射分析方法测定了化合物3f的结构．

a: R=4-Cl,Ar=4-CH3C6H4;b: R=3,4-(OCH2O),Ar=4-CH3C6H4;c: R=4-benzoxazolyl,Ar=4-CH3C6H4;
d: R=3,4-(OCH2O),Ar=4-ClC6H4;e: R=4-benzoxazolyl,Ar=4-ClC6H4;f: R=4-CH3,Ar=4-ClC6H4;g: R=2-Cl,Ar=3-Cl-4-CH3C6H3;h: R=4-CH3O,Ar=3-Cl-4-CH3C6H3;i: R=4-Cl,Ar=C6H5

图1 4-噻唑啉酮类化合物的合成

1 实验部分

1.1 仪器与试剂

X-24型数字显示显微熔点仪(北京泰克仪器有限公司),温度计未经校正;Bruker DPX 400MHz核磁共振仪(溶剂为CDCl3);Yanaco MT-3CHN 元素分析仪;BRUCKER SMART 1000 X射线衍射仪．

4-苯并恶唑基苯甲醛自制,其他试剂均为市售化学纯或分析纯．

1.2 4-噻唑啉酮类化合物的合成

将1mmol醛,1mmol胺,1mmol巯基乙酸和0.064g (0.25mmol)碘单质加入到盛有2 mL冰醋酸的圆底烧瓶中,室温下搅拌反应2～4h(TLC检测),反应完成后,将反应液倒入50mL冰水中并搅拌5min,抽滤,固体物用无水乙醇重结晶得产物．

2 结果与讨论

图2 化合物3f的分子结构图

该反应在冰醋酸中进行,I2的用量为25%(mol)室温搅拌2～4h即可完成,操作方便、产率高、环境友好,但在相似条件下,反应物中含有强吸电子基团时如-NO2等,几乎得不到预期产物．表1给出了4-噻唑啉酮3a～3i合成的时间、产率和熔点．所有产物结构经核磁共振氢谱和元素分析表征,噻唑烷环中的CH由于与吸电子原子N及S相连,导致其质子化学位移向低场移动,一般在δ6.10附近;目标化合物噻唑烷环中潜手性碳原子C(2)上的两个质子HA和HB出现在δ 3.79～4.02附近,相互偶合裂分为双重峰属于典型的AB体系;把目标化合物3f溶于无水乙醇中,静置,两周后逐渐长成浅灰色晶体.该晶体属于三斜晶系,空间群为P-1,晶胞参数：a=0.81506(12)nm,b=0.96414(14)nm,c=0.99470(15)nm,α=87.777°(2),β=74.946°(2),γ=72.030°(2),V=0.71729(18)nm3,Z=2,Dc=1.407g/cm3,μ=0.406mm-1,F(000)=316,R=0.0503,wR=0.1106.图2是化合物3f的分子结构图,部分键长、键角见表2．

表1 4-噻唑啉酮(3a～3i)合成的反应时间、产物熔点和产率

3a: 白色晶体,1H NMR(CDCl3,400 MHz)δ: 7.01～7.29 (m,8H,ArH),6.05 (s,1H,CH),4.01 (d,1H,CH2S),3.89 (d,1H,CH2S),2.28 (s,3H,CH3).Anal.calcd for C16H14ClNOS: C 63.25,H 4.64,N 4.61;found C 63.47,H 4.71,N 4.34.

3b: 浅黄色晶体,1H NMR(CDCl3,400 MHz)δ: 6.67～7.27 (m,7H,ArH),6.00 (s,1H,CH),5.95 (s,2H,OCH2O),3.98 (d,1H,CH2S),3.87 (d,1H,CH2S),2.28 (s,3H,CH3).Anal.calcd for C17H15NO3S: C 65.16,H 4.82,N 4.47;found C 65.37,H 4.58,N 4.61.

3c: 浅黄色晶体,1H NMR(CDCl3,400 MHz)δ: 7.05～8.10 (m,12H,ArH),6.13 (s,1H,CH),4.06 (d,1H,CH2S),4.02 (d,1H,CH2S),2.26 (s,3H,CH3).Anal.calcd for C23H18N2O2S: C 71.48,H 4.69,N 7.25;found C 71.37,H 4.48,N 7.51.

3d: 浅黄色晶体,1H NMR(CDCl3,400 MHz)δ: 6.68～7.29 (m,7H,ArH),6.02 (s,1H,CH),5.96 (s,2H,OCH2O),3.98 (d,1H,CH2S),3.87 (d,1H,CH2S).Anal.calcd for C16H12ClNO3S: C 57.57,H 3.62,N 4.20;found C 57.37,H 3.38,N 4.03.

3e: 浅黄色晶体,1H NMR(CDCl3,400 MHz)δ: 7.15～8.46 (m,12H,ArH),6.14 (s,1H,CH),4.02 (d,1H,CH2S),3.98 (d,1H,CH2S).Anal.calcd for C22H15ClN2O2S: C 64.94,H 3.72,N 6.88;found C 65.17,H 3.57,N 7.03.

3f: 白色晶体,1H NMR(CDCl3,400 MHz)δ: 7.11～7.34 (m,8H,ArH),6.06 (s,1H,CH),3.98 (d,1H,CH2S),3.87 (d,1H,CH2S),2.32 (s,3H,CH3).Anal.calcd for C16H14ClNOS: C 63.25,H 4.64,N 4.61;found C 63.17,H 4.85,N 4.77.

3g: 浅灰色晶体,1H NMR(CDCl3,300 MHz)δ: 7.03 7.41 (m,7H,ArH),6.50 (s,1H,CH),3.92 (d,1H,CH2S),3.79 (d,1H,CH2S),2.28 (s,3H,CH3).Anal.calcd for C16H13Cl2NOS: C 56.81,H 3.87,N 4.14;found C 56.67,H 3.71,N 4.01.

3h: 棕色晶体,1H NMR(CDCl3,300 MHz)δ: 6.79 7.26 (m,7H,ArH),6.02 (s,1H,CH),3.95 (d,1H,CH2S),3.85 (d,1H,CH2S),3.76 (s,3H,OCH3),2.26 (s,3H,CH3).Anal.calcd for C17H16ClNO2S: C 61.16,H 4.83,N 4.20;found C 60.93,H 4.62,N 4.29.

3i: 白色固体,1H NMR(CDCl3,400 MHz)δ: 7.12～7.34 (m,9H,ArH),6.07 (s,1H,CH),3.98 (d,1H,CH2S),3.87 (d,1H,CH2S),2.32 (s,3H,CH3).Anal.calcd for C15H12ClNOS: C 62.17,H 4.17,N 4.83;found C 61.99,H 4.32,N 4.91.

表2 化合物3f的部分键长(10-1 nm)和键角(°)

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