CN104140402A - 一种苯并噻唑类化合物及其制备方法 - Google Patents
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- -1 Benzothiazole compound Chemical class 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
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- 229940125898 compound 5 Drugs 0.000 claims abstract description 17
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims abstract description 13
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000003513 alkali Substances 0.000 claims abstract description 8
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- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910000024 caesium carbonate Inorganic materials 0.000 claims abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 45
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 33
- 229940125782 compound 2 Drugs 0.000 claims description 17
- 229940126214 compound 3 Drugs 0.000 claims description 17
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 claims description 11
- 229940125904 compound 1 Drugs 0.000 claims description 11
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 9
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
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- SLCMRYDRRSPOKH-UHFFFAOYSA-N 2-propan-2-yl-1,3-benzothiazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2SC(C(C)C)=NC2=C1 SLCMRYDRRSPOKH-UHFFFAOYSA-N 0.000 abstract 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 abstract 1
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- YEVANZOTPHUOCL-UHFFFAOYSA-N CC(C)C(Nc(cc(cc1)C(OC)=O)c1Cl)=S Chemical compound CC(C)C(Nc(cc(cc1)C(OC)=O)c1Cl)=S YEVANZOTPHUOCL-UHFFFAOYSA-N 0.000 description 1
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- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
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- 239000012530 fluid Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
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- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
- A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/53—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
- C07C233/54—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
- C07C327/38—Amides of thiocarboxylic acids
- C07C327/40—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C327/42—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of a saturated carbon skeleton
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Abstract
本发明涉及一种苯并噻唑类化合物及其制备方法，该化合物为2-异丙基-5-羧基苯并噻唑，制备方法如下：(1)化合物4用劳森试剂制取硫代酰胺，得到化合物5；所述化合物5用碳酸铯做碱关噻唑环，得到化合物6；(2)将化合物6在碱性条件下水解得到终产物化合物7；该制备方法通过对反应过程中反应条件的合理把控，可以得到纯度15％以上的萃取物，萃取率达到95％以上，比旧工艺提高了1.9倍，总制造成本降低约447元/kg，全流程提取时间由120h缩短约100h，且节约能源、劳动力和大量的有机溶剂，特别是石油醚。
Description
技术领域
本发明涉及化合物生产领域，尤其是一种苯并噻唑类化合物及其制备方法。
背景技术
根据Oxocyclohexenylcarbonylbenzoheterocycles as herbicides,PCT Int.Appl.(2000),WO2000068210A120001116等文献记载，苯并噻唑类化合物广泛存在于具有生物活性的天然产物和药物分子中，在治疗癌症，心血管和神经***疾病方面具有巨大的药用价值。由于其良好的药理活性及潜在的药用价值，现阶段噻唑衍生物的合成倍受关注。
发明内容
本发明所要解决的技术问题在于提供一种苯并噻唑类化合物。
本发明所要解决的另一技术问题在于提供上述苯并噻唑类化合物的制备方法。
为解决上述技术问题，本发明的技术方案是：
一种苯并噻唑类化合物，2-异丙基-5-羧基苯并噻唑，其结构式为(Ⅰ)所示，
优选的，上述苯并噻唑类化合物，2-异丙基-5-羧基苯并噻唑为淡白色固体，其核磁共振氢谱数据为1H-NMR(DMSO；400MHZ)1.422(d,6H)3.433(m,1H)7.956(d,1H)8.180(d,1H)8.425(s,1H)13.102(s,1H)。
上述苯并噻唑类化合物的制备方法，具体步骤如下：
(1)化合物4用劳森试剂制取硫代酰胺，得到化合物5；所述化合物5用碳酸铯做碱关噻唑环，得到化合物6；
(2)将化合物6在碱性条件下水解得到终产物化合物7，其中，
为新化合物，上述苯并噻唑类化合物的制备方法，具体步骤如下：
(1)化合物1在甲醇和浓硫酸条件下，将苯环上羧酸酯化做成甲酯，得到化合物2；
(2)化合物2用Raney-Ni将硝基还原为氨基，得到化合物3；
(3)化合物3以三乙胺和异丁酰氯为条件上异丙基，得到化合物4；
(4)化合物4用劳森试剂制取硫代酰胺，得到化合物5；所述化合物5用碳酸铯做碱关噻唑环，得到化合物6；
(5)将化合物6在碱性条件下水解得到终产物化合物7，其中
优选的，上述苯并噻唑类化合物的制备方法，所述化合物4-6作为中间产物，为新化合物。
上述苯并噻唑类化合物的制备方法的具体反应方程式如图2所示。
优选的，上述苯并噻唑类化合物的制备方法，所述步骤(1)中化合物1与甲醇和浓硫酸的用量按g/ml/ml计为10-30/120-170/1-6， 进一步优选为20/150/4。
优选的，上述苯并噻唑类化合物的制备方法，所述步骤(2)中化合物2与Raney-Ni用量的重量比为15:1-3，进一步优选为15：1.5。
优选的，上述苯并噻唑类化合物的制备方法，所述步骤(3)中化合物3与三乙胺和异丁酰氯用量的重量比为10-20:12-15:10-18，进一步优选为12.9：14.1：11.1。
优选的，上述苯并噻唑类化合物的制备方法，所述步骤(4)中化合物4与劳森试剂及碳酸铯用量的重量比为30-45:13-21:42-47，进一步优选为34：16.9：45。
本发明的有益效果是：
上述苯并噻唑类化合物的制备方法，通过对反应过程中反应条件的合理把控，可以得到纯度15％以上的萃取物，萃取率达到95％以上，比旧工艺提高了1.9倍，总制造成本降低约447元/kg，全流程提取时间由120h缩短约100h，且节约能源、劳动力和大量的有机溶剂，特别是汽油。
可见，采用超临界萃取技术，SC-CO2萃取为环境无害工艺，而且超临界流体不仅具有与液体溶剂相当的萃取能力，具有优良的传质效果，同时不仅避免了大量有机溶剂的使用，也防止了提取过程对人体健康的危害和对环境的污染，且具有提取时间短、萃取率高、节约能源及生产成本等优势，适合规模化工业生产的需要。
附图说明
图1为2-异丙基-5-羧基苯并噻唑的HNMR谱图；
图2为2-异丙基-5-羧基苯并噻唑的制备方法的合成路线图。
具体实施方式
为了使本领域的技术人员更好的理解本发明的技术方案，下面结合具体实施方式对本发明所述技术方案作进一步的详细说明。
实施例1
如图1-2所示，2-异丙基-5-羧基苯并噻唑的制备方法，具体步骤如下：
(1)将20g化合物1溶于150mL甲醇中，再慢慢滴加4mL浓硫酸，滴加完毕，升温至回流过夜；反应完毕，将体系浓缩，再向剩余物中加入100mL水，碳酸氢钠调pH为8，析出固体过滤，滤饼烘干得化合物2，为白色固体21.24g，收率99.3％。TLC(薄层色谱)信息(石油醚：乙酸乙酯＝3:1)：原料Rf＝0.3，产品Rf＝0.7。
(2)将15g化合物2加入到200mL甲醇中，再加入1.5gRaney-Ni，用氢气置换3次室温搅拌15h。待原料完全消失后，反应液经硅藻土过滤，滤饼用甲醇洗涤三次，滤液直接浓缩过柱(石油醚：乙酸乙酯＝4:1)得化合物3，为黄色固体12.9g，产率99％。TLC信息(石油醚：乙酸乙酯＝3:1)：原料Rf＝0.7，产品Rf＝0.6。
(3)室温将12.9g化合物3溶于130mL二氯甲烷，氮气保护下加入14.1g三乙胺，加毕，将体系降温至0℃，慢慢滴加11.1g异丁酰氯，30min滴加完毕，自然恢复至室温并搅拌15小时至原料消失，然后将反应体系直接浓缩得到化合物4，为淡黄色固体(粗品)34g。TLC信息(石油醚：乙酸乙酯＝5:1)：原料Rf＝0.5，产品Rf＝0.4。
(4)室温下向34g化合物4中加入280mL甲苯，并于氮气保护下加入16.9g劳森试剂，然后将体系升温至120℃搅拌15小时；待原料反应完全，所得化合物5未经处理，直接将体系降温，向上述反应液中加入45.0g Cs2CO3并加热体系至回流搅拌15小时至原料消失，将反应液直接浓缩，过柱纯化(500克200-300目硅胶柱子)得化合物6，为淡黄色固体9g，三步收率55％。TLC信息(石油醚：乙酸乙酯＝5:1)：原料Rf＝0.5，产品Rf＝0.8。
1H-NMR(CDCl3；400MHZ)1.492(d,6H)3.436(m,1H)3.960(s,3H)7.887(d,1H) 8.021(d,1H)8.651(s,1H)
(5)将1.1g化合物6溶于11mL甲醇中，再向其中加入0.56g氢氧化钠，然后将体系升温至45o C搅拌15小时；待反应完全，将反应体系浓缩，再向浓缩后的剩余物中加入20mL水溶解，所得水溶液用甲基叔丁基醚萃取一次；水相用10％盐酸调pH为3-4，析出固体，过滤，滤饼以水洗涤2次，再用油泵拉干，得到化合物7，为淡白色固体0.8g，收率77％。TLC信息(石油醚：乙酸乙酯＝10:1)：原料Rf＝0.5，产品Rf＝0.1。1H-NMR(DMSO；400MHZ)1.422(d,6H)3.433(m,1H)7.956(d,1H)8.180(d,1H)8.425(s,1H)13.102(s,1H)。
实施例2
2-异丙基-5-羧基苯并噻唑的制备方法，步骤及产物同实施例1，具体步骤如下：
(1)化合物1在甲醇和浓硫酸条件下，将苯环上羧酸酯化做成甲酯，得到化合物2，其中，所述化合物1与甲醇和浓硫酸的用量按g/ml/ml计为10/170/6；
(2)化合物2用Raney-Ni将硝基还原为氨基，得到化合物3，其中所述化合物2与Raney-Ni用量的重量比为15:3；
(3)化合物3以三乙胺和异丁酰氯为条件上异丙基，得到化合物4，其中，所述化合物3与三乙胺和异丁酰氯用量的重量比为10:12:18；
(4)化合物4用劳森试剂制取硫代酰胺，得到化合物5，其中，所述化合物5用碳酸铯做碱关噻唑环，得到化合物6，其中，所述化合物4与劳森试剂及碳酸铯用量的重量比为30:13:47；
(5)将化合物6在碱性条件下水解得到终产物化合物7。
实施例3
2-异丙基-5-羧基苯并噻唑的制备方法，步骤及产物同实施例1，具体步骤如下：
(1)化合物1在甲醇和浓硫酸条件下，将苯环上羧酸酯化做成甲酯，得到化合物2，其中，所述化合物1与甲醇和浓硫酸的用量按g/ml/ml计为30/120/1；
(2)化合物2用Raney-Ni将硝基还原为氨基，得到化合物3，其中，所述化合物2与Raney-Ni用量的重量比为15:1；
(3)化合物3以三乙胺和异丁酰氯为条件上异丙基，得到化合物4，其中，所述化合物3与三乙胺和异丁酰氯用量的重量比为20:15:10；
(4)化合物4用劳森试剂制取硫代酰胺，得到化合物5，其中，所述化合物5用碳酸铯做碱关噻唑环，得到化合物6，其中，所述化合物4与劳森试剂及碳酸铯用量的重量比为45:21:42；
(5)将化合物6在碱性条件下水解得到终产物化合物7。
实施例4
2-异丙基-5-羧基苯并噻唑的制备方法，步骤及产物同实施例1，具体步骤如下：
(1)化合物1在甲醇和浓硫酸条件下，将苯环上羧酸酯化做成甲酯，得到化合物2，其中，所述化合物1与甲醇和浓硫酸的用量按g/ml/ml计为20/140/5；
(2)化合物2用Raney-Ni将硝基还原为氨基，得到化合物3，其中，所述化合物2与Raney-Ni用量的重量比为15:2；
(3)化合物3以三乙胺和异丁酰氯为条件上异丙基，得到化合物4，其中，所述化合物3与三乙胺和异丁酰氯用量的重量比为17:13:16；
(4)化合物4用劳森试剂制取硫代酰胺，得到化合物5，其中，所述化合物5用碳酸铯做碱关噻唑环，得到化合物6，其中，所述化合物4与劳森试剂及碳酸铯用量的重量比为40:18:44；
(5)将化合物6在碱性条件下水解得到终产物化合物7。
应用试验例
应用实施例1所得化合物针对桃蚜(green peach aphid)进行测试，在叶喷雾测定对桃蚜进行杀虫测试中，将在3英寸罐中生长的卷心菜幼苗用作试验底物，用20-50个桃蚜对所述幼苗进行侵害1-2天，然后进行化学应用，每种处理使用四株幼苗，将化合物5mg溶于2mL甲醇溶液中，再用5倍体积的水稀释以得到溶液，将溶液以喷雾方式喷洒到卷心菜叶子的两面。三天后，经检测桃蚜死亡率达83％。
上述参照具体实施方式对该一种苯并噻唑类化合物及其制备方法进行的详细描述，是说明性的而不是限定性的，可按照所限定范围列举出若干个实施例，因此在不脱离本发明总体构思下的变化和修改，应属本发明的保护范 围之内。
Claims (9)
1.一种苯并噻唑类化合物，其特征在于：为2-异丙基-5-羧基苯并噻唑，其结构式为(Ⅰ)所示，
。
2.根据权利要求1所述的苯并噻唑类化合物，其特征在于：所述2-异丙基-5-羧基苯并噻唑为淡白色固体，其核磁共振氢谱数据为1H-NMR(DMSO；400MHZ)1.422(d,6H)3.433(m,1H)7.956(d,1H)8.180(d,1H)8.425(s,1H)13.102(s,1H)。
3.权利要求1或2所述的苯并噻唑类化合物的制备方法，其特征在于：具体步骤如下：
(1)化合物4用劳森试剂制取硫代酰胺，得到化合物5；所述化合物5用碳酸铯做碱关噻唑环，得到化合物6；
(2)将化合物6在碱性条件下水解得到终产物化合物7，其中，
4.根据权利要求3所述的苯并噻唑类化合物的制备方法，其特征在于：具体步骤如下：
(1)化合物1在甲醇和浓硫酸条件下，将苯环上羧酸酯化做成甲酯，得到化合物2；
(2)化合物2用Raney-Ni将硝基还原为氨基，得到化合物3；
(3)化合物3以三乙胺和异丁酰氯为条件上异丙基，得到化合物4；
(4)化合物4用劳森试剂制取硫代酰胺，得到化合物5；所述化合物5用碳酸铯做碱关噻唑环，得到化合物6；
(5)将化合物6在碱性条件下水解得到终产物化合物7，其中
5.根据权利要求3或4所述的苯并噻唑类化合物的制备方法，其特征在于：所述化合物4-6作为中间产物，为新化合物。
6.根据权利要求4所述的苯并噻唑类化合物的制备方法，其特征在于：所述步骤(1)中化合物1与甲醇和浓硫酸的用量按g/ml/ml计为10-30/120-170/1-6。
7.根据权利要求4所述的苯并噻唑类化合物的制备方法，其特征在于：所述步骤(2)中化合物2与Raney-Ni用量的重量比为15:1-3。
8.根据权利要求4所述的苯并噻唑类化合物的制备方法，其特征在于：所述步骤(3)中化合物3与三乙胺和异丁酰氯用量的重量比为10-20:12-15:10-18。
9.根据权利要求4所述的苯并噻唑类化合物的制备方法，其特征在于：所述步骤(4)中化合物4与劳森试剂及碳酸铯用量的重量比为30-45:13-21:42-47。
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