CN108358865B - 一种多取代噻唑类化合物的制备方法 - Google Patents
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- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Abstract
本发明提供了一种新型的利用烯胺和硫磺为原料在空气条件下合成多取代的噻唑类化合物的方法。本发明在以无水三氯化铁为催化剂和二甲基亚砜为溶剂的反应体系下简单直接合成了多取代的噻唑类化合物。该反应是首次利用烯胺和硫磺为底物合成多取代的噻唑类化合物，且硫磺为硫原子的供体，反应步骤少，反应对空气不敏感。同时本发明还具有反应条件简单，廉价，操作安全，收率高等特点，具有极大的工业化应用价值。
Description
技术领域
本发明属于有机合成技术领域，具体涉及一种多取代噻唑化合物的制备方法。
背景技术
多取代噻唑是一类重要的化合物，该类化合物不仅是许多天然产物的核心结构单元，而且在生物、医药等领域有着广泛的应用。例如，抗疟疾药物，抗HIV药物，抗癌药物等中都含有多取代噻唑骨架。因此多取代噻唑化合物合成的方法学研究一直被人们所关注。
近年来多取代噻唑化合物的合成方法取得了较好的进展。列举如下：
(1)以α-对甲苯磺酰氧基酮、炔基碘鎓和硫脲为底物：
Hideo Togo1a和Srikanth Venkatraman1b小组分别以α-对甲苯磺酰氧基酮、炔基碘鎓和硫脲为反应底物，在碱性环境下反应均可生成取代基噻唑。
(2)以α-氨基-β-酮酯和Lawesson's试剂为底物：
Santos Fustero小组发现α-氨基-β-酮酯和Lawesson's试剂为原料，在四氢呋喃溶液中回流，一段时间后通过TCL检测可获得取代基的噻唑。2
(3)以三(1-丙烯基)胺和硫磺为底物：
G.K.Musorin小组发现以三(1-丙烯基)胺和硫磺为原料，在DMF或者DMSO中加热至50℃，通过分子内的环化反应生成5-甲基-2-乙基噻唑。3
(4)以烯胺和亚硫酰氯为底物：
Kanchugarakoppal S.Rangappa小组以烯胺和亚硫酰氯为原料，在DMAP 的作用下，烯胺酮通过对亚硫酰氯的亲核进攻，随后经过HCl的消除、去质子化、分子内环化及脱氧一系列过程，最终合成多取代的噻唑化合物。4
(4)以N-苄基芳胺和硫磺为底物：
Guobo Deng小组以N-苄基芳胺和硫磺为原料，DMSO为氧化剂，氧化 N-苄基芳胺为亚胺，随后经过硫的亲电、亲核进攻、分子内的环化和氧化芳构化一系列的过程，最终生成2-苯基苯并噻唑。5
(5)以芳基胺、苯甲醛和硫磺为底物：
Guo-Jun Deng小组以芳基胺、苯甲醛和硫磺为原料，KI为催化剂，芳基胺与苯甲醛首先通过脱水缩合形成亚胺，随后经历硫对亚胺的亲电进攻、脱硫、去质子化、亲核环化及氧化芳构化一系列过程，最终合成苯并噻唑。另外一种反应路径是由硫对亚胺的亲核开始的一系列过程。6
(6)以芳基醛、腈基胺和硫磺为底物：
Eric Romeo小组以芳基醛、腈基胺和硫磺为原料，在碱性环境下，芳基醛与腈基胺先进行脱水缩合形成亚胺，亚胺随后经历互变异构、硫的亲电进攻、环化、互变异构一系列过程，最后形成取代基的噻唑。7
以上几种方法的缺点是原料制备方法复杂，反应条件苛刻，原料不稳定，反应成本较高，无法实现工业化应用，其次至今没有提供很好的能够简单合成取代基的噻唑的制备方法。
本发明所要解决的技术问题在于提供简单高效全新的多取代噻唑化合物的制备方法。
为解决上述技术问题，本发明采用的技术方案是：一种多取代噻唑化合物的制备方法，包括以下步骤：在反应器中加入具有通式I和硫磺的化合物，溶剂二甲基亚砜(DMSO)，催化剂为无水三氯化铁，空气中在140℃的油浴锅中反应7.0h，薄层色谱监测反应进程，直至反应完全；用乙酸乙酯和饱和食盐水萃取，用无水硫酸钠干燥，减压蒸出溶剂，后用石油醚/乙酸乙酯＝40/1的流动相经硅胶柱层析分离纯化，得到化合物III，反应方程式如下：
方程式中：R1为芳基、烷基，R2为芳基、烷基，R3为芳基、烷基、烷氧基。
上述的这种多取代噻唑化合物的制备方法，其特征在于，原料廉价易得且在空气环境下反应，在催化氧化条件下使烯胺氧化为亚胺，随后硫对亚胺中间体进行亲电或者亲核两种方式进攻，最终通过分子内环化氧化得到最终产物。
本发明与现有技术相比具有以下优点：
1、本发明所用原料廉价易得，在空气环境下反应，操作简便，底物兼容性好，产率高等优点。
2、本发明使用硫磺为硫原子的供体进行噻唑的构建，整个反应过程包括了氧化环化的过程。
3、本发明不需要昂贵的催化剂且操作较安全。
下面通过实施例，对本发明技术方案做进一步的详细说明。具体实施方式
实施例1：本实施例的制备方法包括以下步骤：
在反应管中依次加入化合物Ia(0.30mmol)、硫磺(0.9mmol)、DMSO(2 mL)、FeCl3(0.03mmol)，放在140℃的油浴锅中，反应7.0h，薄层色谱监测反应进程，直至反应完全；用乙酸乙酯和饱和食盐水萃取，用无水硫酸钠干燥，减压蒸出溶剂，残渣用石油醚/乙酸乙酯＝40/1的流动相经硅胶柱层析分离纯化，得到化合物IIIa，收率99％。反应方程式如下：
实施例1所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝8.08-8.06(m,2H),7.70-7.67(m,2H), 7.54-7.52(m,2H),7.49-7.45(m,3H),7.40-7.35(m,1H),7.24-7.18(m,5H)；13C NMR(100MHz,CDCl3,ppm):δ＝189.6,170.1,158.8,137.2,134.3,133.0,132.9, 131.5,131.3,129.9,129.8,129.2,128.9,128.2,128.1,127.1；HRMS calcd for C22H16NOS[M+H]+342.0947；found:342.0946.
实施例2所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.89-7.87(m,1H),7.74-7.71(m,2H), 7.56-7.53(m,2H),7.42-7.28(m,4H),7.26-7.17(m,5H),2.72(s,3H)；13C NMR (100MHz,CDCl3,ppm):δ＝189.8,169.9,157.9,137.2,137.1,134.3,133.1,132.2, 131.9,131.8,130.4,130.2,129.9,129.8,128.9,128.3,128.2,126.5,22.0；HRMS calcd for C23H18NOS[M+H]+356.1104；found:356.1100.
实施例3所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.92(s,1H),7.87-7.85(d,J＝7.6Hz, 1H),7.70-7.68(d,J＝8.0Hz,2H),7.54-7.52(m,2H),7.41-7.30(m,3H),7.25- 7.19(m,5H),2.44(s,3H)；13C NMR(100MHz,CDCl3,ppm):δ＝189.6,170.4, 158.8,139.1,137.3,134.4,133.0,132.9,132.1,131.4,129.9,129.8,129.1,128.9, 128.2,128.1,127.6,124.3,21.5；HRMScalcd for C23H18NOS[M+H]+356.1104； found:356.1110.
实施例4所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.98-7.96(d,J＝8.0Hz,2H),7.69- 7.67(d,J＝8.0Hz,2H),7.53-7.51(m,2H),7.40-7.36(m,1H),7.29-7.18(m,7H), 2.42(s,3H)；13C NMR(100MHz,CDCl3,ppm):δ＝189.6,170.4,158.9,141.8, 137.3,134.4,132.9,131.1,130.4,130.0,129.9,129.8,128.9,128.2,128.1,127.0, 21.7；HRMS calcd for C23H18NOS[M+H]+356.1104；found:356.1101.
实施例5所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.69-7.67(m,2H),7.64-7.60(m,2H), 7.54-7.52(m,2H),7.39-7.35(m,2H),7.24-7.18(m,5H),7.04-7.01(m,1H),3.87 (s,3H)；13C NMR(100MHz,CDCl3,ppm):δ＝189.5,169.9,160.2,158.7,137.2, 134.3,134.2,133.1,131.6,130.3,129.9,129.8,129.0,128.3,128.2,119.7,117.5, 111.7,55.6；HRMS calcd forC23H18NO2S[M+H]+372.1053；found:372.1045.
实施例6所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.69-7.67(m,2H),7.54-7.52(m,2H), 7.39-7.36(m,1H),7.25-7.16(m,7H),6.59-6.58(m,1H),3.85(s,6H)；13C NMR (100MHz,CDCl3,ppm):δ＝189.5,169.9,161.3,158.7,137.2,134.7,134.3,133.1, 131.6,129.9,129.8,129.0,128.3,128.1,104.9,103.6,55.7；HRMS calcd for C24H20NO3S[M+H]+402.1159；found:402.1152.
实施例7所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝8.49-8.44(m,1H),7.71-7.70(m,2H), 7.57-7.54(m,2H),7.48-7.38(m,2H),7.31-7.19(m,7H)；13C NMR(100MHz, CDCl3,ppm):δ＝189.7,162.2-162.1(d,J＝5.0Hz,1C),161.8-159.3(d,J＝252.0 Hz,1C),157.5,137.3,134.2,133.1,132.4,132.3,129.9,129.8,129.2,129.0,128.3, 128.2,124.9-124.8(d,J＝3.0Hz,1C),121.0-120.9(d,J＝11.0Hz,1C),116.5- 116.3(d,J＝22.0Hz,1C)；HRMS calcdfor C22H15FNOS[M+H]+360.0853；found: 360.0848.
实施例8所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.84-7.79(m,2H),7.70-7.67(m,2H), 7.54-7.51(m,2H),7.46-7.37(m,2H),7.24-7.15(m,6H)；13C NMR(100MHz, CDCl3,ppm):δ＝189.4,168.4-168.3(d,J＝3.0Hz,1C),164.4-161.9(d,J＝246.0 Hz,1C),158.7,137.0,135.0-134.9(d,J＝8.0Hz,1C),134.1,133.2,132.0,130.9- 130.8(d,J＝8.0Hz,1C),129.8,129.1,128.3,128.2,122.9-122.8(d,J＝3.0Hz,1 C),118.2-118.0(d,J＝22.0Hz,1C),114.0,113.7；HRMS calcd for C22H15FNOS [M+H]+360.0853；found:360.0859.
实施例9所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝8.08-8.05(m,2H),7.69-7.67(d,J＝ 7.6Hz,2H),7.52-7.50(m,2H),7.40-7.36(m,1H),7.25-7.14(m,7H)；13C NMR (100MHz,CDCl3,ppm):δ＝189.5,168.8,165.9-163.4(d,J＝251.0Hz,1C),158.8, 137.1,134.2,133.1,131.6,129.8-129.8(d,J＝3.0Hz,1C),129.4,129.3,129.2, 129.1,129.0,128.3-128.2(d,J＝8.0Hz,1C),116.5-116.3(d,J＝22.0Hz,1C)； HRMS calcd for C22H15FNOS[M+H]+360.0853；found:360.0856.
实施例10所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝8.01-7.98(m,2H),7.69-7.67(m,2H), 7.52-7.50(m,2H),7.46-7.42(m,2H),7.40-7.36(m,1H),7.25-7.18(m,5H)；13C NMR(100MHz,CDCl3,ppm):δ＝189.4,168.6,158.8,137.3,137.1,134.1,133.1, 131.8,131.5,129.8,129.5,129.1,128.3,128.2；HRMS calcd for C22H15ClNOS [M+H]+376.0558；found:376.0566.
实施例11所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝8.47-8.45(d,J＝8.8Hz,1H),7.72- 7.70(m,2H),7.55-7.53(m,3H),7.43-7.38(m,2H),7.27-7.20(m,5H)；13C NMR (100MHz,CDCl3,ppm):δ＝189.6,163.8,157.1,137.1,136.8,134.0,133.3,133.1, 132.9,131.9,130.6,130.0129.9,129.8,129.0,128.3,128.2,127.8；HRMS calcd for C22H14Cl2NOS[M+H]+410.0168；found:410.0172.
实施例12所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.95-7.92(m,2H),7.69-7.67(m,2H), 7.62-7.60(m,2H),7.52-7.50(m,2H),7.41-7.37(m,1H),7.25-7.19(m,5H)；13C NMR(100MHz,CDCl3,ppm):δ＝189.4,168.7,158.8,137.1,134.1,133.1,132.4, 131.9,131.8,129.8,129.1,128.4,128.3,128.2,125.7；HRMS calcd for C22H15BrNOS[M+H]+420.0052；found:420.0060.
实施例13所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.66-7.64(m,2H),7.44-7.42(m,2H), 7.39-7.35(m,1H),7.23-7.13(m,5H),3.09-3.05(m,2H),1.96-1.87(m,2H),1.11- 1.07(m,3H)；13CNMR(100MHz,CDCl3,ppm):δ＝189.7,174.5,157.7,137.2, 134.3,132.9,131.1,129.8,129.7,128.7,128.2,128.1,35.9,23.5,13.9；HRMS calcd for C19H18NOS[M+H]+308.1104；found:308.1109.
实施例14所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.66-7.63(m,2H),7.44-7.42(m,2H), 7.39-7.35(m,1H),7.23-7.14(m,5H),3.10-3.06(m,2H),1.96-1.84(m,2H),1.50- 1.43(m,2H),1.39-1.25(m,6H),0.91-0.88(m,3H)；13C NMR(100MHz,CDCl3, ppm):δ＝189.6,174.8,157.7,137.1,134.2,132.8,131.0,129.7,129.6,128.7,128.1, 128.0,33.9,31.7,30.1,29.2,29.0,22.7,14.2；HRMS calcd for C23H26NOS[M+H]+ 364.1730；found:364.1726.
实施例15所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.65-7.63(m,2H),7.44-7.42(m,2H), 7.38-7.34(m,1H),7.22-7.12(m,5H),3.09-3.06(m,2H),1.91-1.83(m,2H),1.48- 1.43(m,2H),1.26(s,26H),0.89-0.86(m,3H)；13C NMR(100MHz,CDCl3,ppm): δ＝189.7,174.8,157.7,137.2,134.3,132.9,131.0,129.8,129.7,128.7,128.2,128.1, 34.0,32.0,30.1,29.8,29.7,29.7,29.6,29.5 29.4,29.3,22.8,14.3；HRMS calcd for C33H46NOS[M+H]+504.3295；found:504.3302.
实施例16所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.69-7.67(m,2H),7.48-7.41(m,3H), 7.27-7.19(m,5H),7.05-6.77(m,1H)；13C NMR(100MHz,CDCl3,ppm):δ＝190.0, 163.3-162.7(t,J＝30.0Hz,1C),157.5,136.3,133.8,133.5,133.2,129.9,129.6, 129.4,128.5,128.4,113.0-108.2(t,J＝239.0Hz,1C)；HRMS calcd for C17H12F2NOS[M+H]+316.0602；found:316.0606.
实施例17所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.66-7.64(m,2H),7.59-7.58(d,J＝ 1.2Hz,1H),7.49-7.47(m,2H),7.39-7.36(m,1H),7.23-7.17(m,6H),6.60-6.58 (m,1H)；13C NMR(100MHz,CDCl3,ppm):δ＝189.3,159.9,159.1,148.6,144.9, 137.2,134.1,132.9,130.9,129.8,129.7,129.0,128.2,128.1,112.8,111.3；HRMS calcd for C20H14NO2S[M+H]+332.0740；found:332.0737.
实施例18所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝9.00-8.98(d,J＝8.4Hz,1H),7.99- 7.91(m,3H),7.78-7.76(m,2H),7.65-7.52(m,5H),7.43-7.39(m,1H),7.28-7.21 (m,5H)；13C NMR(100MHz,CDCl3,ppm):δ＝189.7,169.8,158.3,137.2,134.3, 134.2,133.2,132.0,131.6,130.5,130.0,129.9,129.8,129.2,129.0,128.7,128.3, 128.2,127.9,126.7,125.9,125.2；HRMS calcd for C26H18NOS[M+H]+392.1104； found:392.1110.
实施例19所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝8.62-8.60(m,2H),7.79-7.77(m,2H), 7.69-7.65(m,1H),7.61-7.53(m,4H),7.51-7.47(m,1H),7.34-7.25(m,5H)；13C NMR(100MHz,CDCl3,ppm):δ＝189.5,183.8,167.9,157.9,136.5,136.5,134.7, 134.2,134.0,133.6,131.5,130.0,129.4,129.3,128.7,128.6,128.5；HRMS calcd for C23H16NO2S[M+H]+370.0896；found:370.0891.
实施例20所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝8.01-7.98(m,2H),7.87-7.84(m,2H), 7.63-7.59(m,1H),7.53-7.43(m,5H),2.68(s,3H)；13C NMR(100MHz,CDCl3, ppm):δ＝188.8,170.4,160.6,139.8,132.9,132.8,131.3,129.7,129.2,129.0,128.6, 127.0,18.7；HRMS calcdfor C17H14NOS[M+H]+280.0791；found:280.0788.
实施例21所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝8.00-7.98(m,2H),7.92-7.88(m,2H), 7.49-7.44(m,3H),7.21-7.16(m,2H),2.67(s,3H)；13C NMR(100MHz,CDCl3, ppm):δ＝187.2,170.3,166.7-164.2(d,J＝253.0Hz,1C),160.5,135.9-135.8(d,J ＝3.0Hz,1C),132.7,131.6-131.5(d,J＝9.0Hz,1C),131.3,129.2,129.1,126.9, 115.9-115.6(d,J＝22.0Hz,1C),18.6；HRMS calcd for C17H13FNOS[M+H]+ 298.0697；found:298.0693.
实施例22所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝8.05-8.03(m,2H),7.84-7.82(m,2H), 7.48-7.43(m,6H),4.32-4.27(m,2H),1.32-1.29(m,3H)；13C NMR(100MHz, CDCl3,ppm):δ＝169.9,161.7,160.9,134.3,133.0,131.2,130.0,129.3,129.2,127.9, 127.0,122.5,61.6,14.3；HRMS calcd for C18H16NO2S[M+H]+310.0896；found: 310.0891.
实施例23所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝8.08-8.05(m,2H),7.53-7.47(m,7H), 7.35-7.33(d,J＝8.4Hz,2H),7.25-7.19(m,3H)；13C NMR(100MHz,CDCl3, ppm):δ＝188.5,170.5,159.0,135.9,134.1,132.9,131.5,131.4,131.3,131.2,129.9, 129.3,129.2,128.3,128.1,127.1；HRMS calcd for C22H15BrNOS[M+H]+420.0052；found:420.0041.
实施例24所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝8.08-8.05(m,2H),7.74-7.72(d,J＝ 8.8Hz,2H),7.60-7.58(m,2H),7.49-7.47(m,3H),7.25-7.22(m,3H),6.74-6.72(d, J＝9.2Hz,2H),3.77(s,3H)；13C NMR(100MHz,CDCl3,ppm):δ＝188.0,169.2, 163.6,157.6,134.3,133.0,132.4,131.2,131.0,129.8,129.6,129.1,128.8,128.2, 126.9,113.5,55.5；HRMS calcdfor C23H18NO2S[M+H]+372.1053；found:372.1058.
实施例25所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝8.06-8.04(m,2H),7.74-7.68(m,4H), 7.47-7.46(m,3H),7.28-7.23(m,3H),6.49-6.47(d,J＝9.2Hz,2H),2.99(s,6H)；13C NMR(100MHz,CDCl3,ppm):δ＝187.1,167.9,155.9,153.7,134.5,133.2, 132.6,131.3,130.7,129.3,129.1,128.5,128.2,126.8,124.4,110.5,40.0；HRMS calcd for C24H21N2OS[M+H]+385.1369；found:385.1362.
实施例26所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝8.22-8.20(m,2H),8.02-7.99(m,2H), 7.54-7.46(m,6H)；13C NMR(100MHz,CDCl3,ppm):δ＝171.4,163.4,132.3, 132.1,132.0,130.6,129.4,129.1,128.2,127.3,113.9,98.1；HRMS calcd for C16H11N2S[M+H]+263.0638；found:263.0636.
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Claims (1)
1.一种多取代噻唑的制备方法，包括以下步骤：在反应器中加入具有通式I和II的化合物，溶剂二甲基亚砜(DMSO)，催化剂为无水三氯化铁，空气条件下在140℃的油浴锅中反应7.0h，薄层色谱监测反应进程，直至反应完全；用乙酸乙酯和饱和食盐水萃取，用无水硫酸钠干燥，减压蒸出溶剂，残渣用石油醚/乙酸乙酯＝40/1的流动相经硅胶柱层析分离纯化，得到化合物III，反应方程式如下：
方程式中：R1选自芳基、烷基，R2选自芳基、烷基，R3选自芳基、烷基、烷氧基。
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| "An efficient synthesis of coumarin- and quinolone-annulated thiazole derivatives via ligand-free iron (III)-catalyzed coupling followed by acid-promoted condensation";K.C.Majumdar;《Tetrahedron Letters》;20130814;第54卷(第33期);第4422-4424页 * |
| "Sulfur extrusion from 5(2H)-isothiazolones and 5(2H)-isothiazolethiones to give intermediate imidoylketenes and imidoylthioketenes";Goerdeler, Joachim等;《Chemische Berichte》;19851231;第118卷(第3期);第851-62页 * |
| "Switching Regioselectivity of beta-Ketothioamides by Means of Iodine Catalysis: Synthesis of Thiazolylidenes and 1,4-Dithiines";Wen Li-Rong;《Chem. Eur. J.》;20141231;第20卷;第5028-5033页 * |
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| "噻唑类化合物及苯并噻嗪类化合物的合成研究";李艳丽;《华东师范大学硕士学位论文》;20170715;第二章 * |
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