Preparation method for 3-substituted trifluoromethyl indole

A technology of trifluoromethyl and trifluoromethylbenzene, applied in the field of preparation of 3-position trifluoromethyl-substituted indole, which can solve the problem of low reaction regioselectivity, limited practical use value, difficulty in obtaining o-iodoaniline, etc. problem, to achieve good application prospects, excellent chemical selectivity, and excellent reaction yield

Inactive Publication Date: 2015-12-09
JIANGXI NORMAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, this reaction has certain limitations, such as: the range of substrates is not wide, the starting material o-iodoaniline is not easy to obtain, the reaction regioselectivity is not high, the amount of catalyst is large, the reaction time is long, and the atom economy is not high, which greatly limits the reaction. (Konno,T.; Chae,J.; Ishihara,T.; Yamanaka,H.J.Org.Chem.,2004,69,8251.)

Method used

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  • Preparation method for 3-substituted trifluoromethyl indole
  • Preparation method for 3-substituted trifluoromethyl indole
  • Preparation method for 3-substituted trifluoromethyl indole

Examples

Experimental program
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example 1

[0021]

[0022] In the reaction test tube, add acetanilide successively, catalyst dichloro(pentamethylcyclopentadienyl) rhodium (III) dimer (2.5mol%), oxidant copper acetate (2.0equiv), additive hexafluoroantimonic acid Silver (10mol%AgSbF 6 ) and solvent tert-amyl alcohol (2 mL), and finally trifluoromethylphenylacetylene (2.0 equiv) was added, and the reaction tube was sealed with a rubber stopper. Put the test tube oil bath in a 100°C oil bath with stirring and heating for about 1 hour. During the reaction, TLC was used to detect that the reaction was complete. In the post-treatment, the solvent was spin-dried first, and the pure product N-acetyl-3-trifluoromethyl-2-phenyl-indole compound 3a was directly separated by silica gel column chromatography. Yield: 81%; yellow solid, melting point 73-75°C; 1 HNMR (400MHz, CDCl 3 ,25℃,TMS):δ8.26(1H,d,J=8.4Hz),7.67(1H,d,J=8.0Hz),7.42-7.32(5H,m),7.30-7.25(2H,m) ,1.78(3H,s); 13 CNMR (100MHz, CDCl 3 ,25℃,TMS):δ171.2,138.6(q,J ...

example 2

[0025]

[0026] N-acetyl-3-trifluoromethyl-2-phenyl-7-methyl-indole, yield: 50%; yellow solid, melting point 117-120°C; 1 HNMR (400MHz, CDCl 3 ,25℃,TMS):δ7.58(1H,d,J=7.6Hz),7.44-7.36(5H,m),7.19(1H,t,J=7.6Hz),7.10(1H,d,J=7.6Hz) 7.6Hz), 2.27(3H,s), 1.92(3H,s); 13 CNMR (100MHz, CDCl 3 ,25℃,TMS):δ173.2,138.0(q,J C-F =4.1Hz), 134.5, 130.2, 129.9, 128.6, 127.9, 125.6, 123.8 (q, J C-F =267.4Hz), 123.7, 123.6, 117.7, 117.6, 108.9 (q, J C-F =34.8Hz), 28.7, 20.9; 19 FNMR (376MHz, CDCl 3 ,25℃,TMS):δ-54.21; HRMS(ESI):m / z[M+Na] + calcdfor(C 18 h 14 f 3 NO) Na: 340.0920; found: 340.0929.

example 3

[0028]

[0029] N-acetyl-3-trifluoromethyl-2-phenyl-6-methyl-indole, yield: 62%; yellow solid, melting point 92-94°C; 1 HNMR (400MHz, CDCl 3 ,25℃,TMS):δ8.11(1H,s),7.55(1H,d,J=8.0Hz),7.41-7.35(5H,m),7.11(1H,d,J=8.0Hz),2.42 (3H,s),1.78(3H,s); 13 CNMR (100MHz, CDCl 3 ,25℃,TMS):δ171.4,137.9(q,J C-F =4.1Hz), 136.4, 136.3, 131.2, 130.3, 129.9, 128.6, 125.9, 123.6 (q, J C-F =267.6Hz), 122.7, 119.2(d, J C-F =1.1Hz), 116.1, 111.7(q, J C-F =34.5Hz), 27.6, 21.9; 19 FNMR (376MHz, CDCl 3 ,25℃,TMS):δ-54.47; HRMS(ESI):m / z[M+Na] + calcdfor(C 18 h 14 f 3 NO) Na: 340.0920; found: 340.0926.

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Abstract

The invention discloses a preparation method for 3-substituted trifluoromethyl indole. Various substituted acetanilides are taken as a reaction substrate with a medium to excellent reaction yield, excellent reaction chemical selectivity, and high area selectivity; another isomer (2-substituted trifluoromethyl indole) is monitored to be not detected in detection; the conditions are gentle; the substrate is wide in scope of application (wherein R is H or various electron-donating groups such as CH3, OCH3, SCH3 and the like, as well as various electron withdrawing groups such as NO2, Cl and the like, and Ar is various substituted benzene rings); the preparation method is simple and convenient in operation, relatively low in cost, less in side reaction, high in product purity, convenient in separation and purification, and suitable for large-scale preparation; and a product prepared by the preparation method has a very good application prospect in the biomedicine field.

Description

technical field [0001] The invention relates to the field of organic chemistry, in particular to a method for preparing a 3-position trifluoromethyl-substituted indole. Background technique [0002] The indole skeleton is the core structure of many natural products and drugs. Indole heterocyclic compounds have a broad spectrum of physiological and pharmaceutical activities, so the rapid and efficient synthesis of indole compounds and their diverse modifications have always attracted organic chemists and drugs. Research interests of chemists ((a) Kaushik, N.K.; Kaushik, N.; Attri, P.; Kumar, N.; Kim, C.H.; Verma, A.K.; Choi, E.H. Molecules, 2013, 18, 6620. (b) Patel, H.; Darji, N.; Pillai, J.; Patel, B. Int. J. Drug Res. Tech. 2012, 2, 225. (c) Biswal, S.; Sahoo, U.; , H.K.S.; Banerjee, M.AsianJ.Pharm.Clin.Res.2012,5,1.(d)Kochanowska-Karamyan,A.J.;Hamann,M.T.Chem.Rev.2010,110,4489.(e)d'Ischia, M.; Napolitano, A.; Pezzella, A. in Comprehensive Heterocyclic Chemistry III, Vol...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/10C07D209/60C07D471/04C07D209/12C07D209/26
CPCC07D209/10C07D209/12C07D209/26C07D209/60C07D471/04
Inventor 周宜荣张春艳杨琴彭以元
Owner JIANGXI NORMAL UNIV
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