CN109574905A

CN109574905A - A kind of trifluoromethyl replaces N- acyl group indolin derivatives and preparation method thereof

Info

Publication number: CN109574905A
Application number: CN201811098324.8A
Authority: CN
Inventors: 陈晓岚; 王军超; 於兵; 屈凌波
Original assignee: Zhengzhou University
Current assignee: Zhengzhou University
Priority date: 2018-09-20
Filing date: 2018-09-20
Publication date: 2019-04-05

Abstract

The invention discloses a kind of trifluoromethyl substituted-dihydro Benzazole compounds and preparation method thereof; use the cuprous iodide of catalytic amount; using Togni reagent and N- acetyl group allyl aniline as reactant; dimethyl sulfoxide is as solvent; temperature is controlled at 60-80 DEG C, and reaction 12-24h replaces N- acyl group indolin derivatives through the isolated trifluoromethyl of column chromatographic analysis.The present invention provides a kind of new method that trifluoromethyl substitution N- acyl group indolin derivatives are synthesized using N- acyl group allyl aniline cheap and easy to get as starting material for the first time.This method advantages such as mild, easy to operate with reaction condition.

Description

A kind of trifluoromethyl replaces N- acyl group indolin derivatives and preparation method thereof

Technical field

The present invention relates to the field of chemical synthesis, and in particular to a kind of trifluoromethyl replaces N- acyl group indolin derivatives Preparation.

Background technique

Trifluoromethyl is present in many bioactive molecules, it have enhancing molecule chemistry with metabolic stability, Improve lipophilicity and improves the properties such as the selectivity in conjunction with large biological molecule.Therefore, trifluoro is introduced in small organic molecule The synthetic method of methyl receives the extensive concern of organic chemist and Pharmaceutical Chemist.Present invention firstly provides trifluoromethyls The preparation method for replacing N- acyl group indolin derivatives provides a kind of mild, cheap method synthesis trifluoromethyl substitution N- Acyl group indolin derivatives.The synthesising method reacting condition is mild, opens wide system operation in air under the conditions of 60-80 DEG C, Handy and safe, raw material and catalyst are cheap and easy to get, are a kind of environmental-friendly synthetic methods.

Summary of the invention

Realize that structure is such as the technical scheme is that a kind of trifluoromethyl replaces N- acyl group indolin derivatives Under:

Wherein, R¹For fluorine, chlorine, bromine, iodine, methyl, methoxyl group, trifluoromethyl, ethyl, isopropyl, tert-butyl；R²For hydrogen, methyl.

The trifluoromethyl replaces the preparation method of N- acyl group indolin derivatives, and steps are as follows: by N- acetyl group alkene Propyl aniline, Togni reagent (1- Trifluoromethyl-1,2- benzenesulfonyl -3 (H) -one), cuprous iodide, sodium acetate are added in reaction tube Heating stirring reaction, obtains indoline trifluoromethylation derivative.

The structure of the N- acetyl group allyl aniline is as follows:

The solvent is dimethyl sulfoxide (DMSO), and alkali is sodium acetate, and catalyst is cuprous iodide.

The N- acetyl group allyl aniline, Togni reagent, cuprous iodide, sodium acetate molar ratio be 1:(1-1.5): (0.1-0.5): (1.5-2).

The reaction temperature is 60-80 DEG C, and the reaction time is 12-24 h.

The reaction formula of preparation method of the present invention is as follows:

The beneficial effects of the present invention are: the present invention provides the preparations that a kind of trifluoromethyl replaces N- acyl group indolin derivatives Method, the method directly carry out in air, efficiently synthesize trifluoromethyl using raw material cheap and easy to get and replace N- acyl group two Hydrogen indoles derivative.It is easy to operate and safe involved in this method, with reaction condition mild, good economy performance, environmental-friendly Advantage.

Specific embodiment

Below in conjunction with the embodiment of the present invention, technical solution of the present invention is clearly and completely described, it is clear that described Embodiment be only a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, ability Domain those of ordinary skill every other embodiment obtained under that premise of not paying creative labor, belongs to guarantor of the present invention The range of shield.

Embodiment 1

Trifluoromethyl replaces the preparation method of N- acyl group indolin derivatives, and steps are as follows:

N- acetyl group allyl aniline (0.5 mmol) is added in 10 mL reaction tubes, Togni reagent (0.5 mmol), iodate Cuprous (0.05 mmol), sodium acetate (0.75 mmol) stir 12 hours at 60 DEG C, and silica gel column chromatography is isolated final Product, by N- acetyl group allyl aniline moles be 100 % in terms of, 91 % of Yield of final product.

Specific structure is as follows:

¹H NMR (400 MHz, CDCl₃ δ 8.23 (d, J = 8.1 Hz, 1H), 7.31-7.24 (m, 1H), 7.15 (d, J = 7.6, 1.5 Hz, 1H), 7.09 (t, J = 7.3 Hz, 1H), 4.13 (d, J = 10.7 Hz, 1H), 3.85 (d, J = 10.8 Hz, 1H), 2.61-2.31 (m, 2H), 2.26 (d, J = 1.4 Hz, 3H), 1.49 (s, 3H).¹³C NMR (101 MHz, CDCl₃) δ 168.61, 141.31, 137.52, 128.72, 127.64, 124.86, 124.05, 121.93, 117.28, 60.99, 43.59, 43.31, 43.05, 42.78, 41.06, 26.07, 24.21.¹⁹F NMR (376 MHz, CDCl₃) δ -60.53。

Embodiment 2

4- fluorine N- acetyl group allyl aniline (0.5 mmol) is added in 10 mL reaction tubes, Togni reagent (0.75 mmol), Cuprous iodide (0.05 mmol), sodium acetate (1 mmol) stir 24 hours at 60 DEG C, and silica gel column chromatography is isolated final Product, by N- acetyl group allyl aniline moles be 100 % in terms of, 82 % of Yield of final product.

Specific structure is as follows:

¹H NMR (400 MHz, CDCl₃) δ 8.17 (dd, J = 8.9, 4.9 Hz, 1H), 6.93 (td, J = 8.9, 2.6 Hz, 1H), 6.82 (dd, J = 8.1, 2.7 Hz, 1H), 4.13 (d, J = 10.8 Hz, 1H), 3.84 (d, J = 10.8 Hz, 1H), 2.56-2.39 (m, 2H), 2.23 (s, 3H), 1.51-1.44 (s, 3H).¹³C NMR (101 MHz, CDCl₃) δ 168.33, 160.67, 158.25, 139.38, 139.31, 137.47, 130.90, 130.21, 127.44, 124.68, 118.31, 118.23, 115.12, 114.90, 109.56, 109.32, 61.12, 43.34, 43.07, 42.80, 42.54, 41.06, 25.95, 23.88. ¹⁹F NMR (376 MHz, CDCl₃) δ -60.44, -118.14。

Embodiment 3

4- methoxyl group N- acetyl group allyl aniline (0.5 mmol) is added in 10 mL reaction tubes, Togni reagent (0.75 Mmol), cuprous iodide (0.25 mmol), sodium acetate (1 mmol) stir 24 hours at 80 DEG C, and silica gel column chromatography separates To final product, be 100 % by N- acetyl group allyl aniline moles in terms of, 73 % of Yield of final product.

Specific structure is as follows:

¹H NMR (400 MHz, CDCl₃) δ 8.12 (d, J = 8.8 Hz, 1H), 6.77 (dd, J = 8.8, 2.6 Hz, 1H), 6.66 (d, J = 2.6 Hz, 1H), 4.10 (d, J = 10.8 Hz, 1H), 3.81 (d, J = 10.8 Hz, 1H) , 3.79 (s, 3H), 2.55-2.38 (m, 2H), 2.21 (s, 3H), 1.46 (s, 3H).¹³C NMR (101 MHz, CDCl₃) δ 167.91, 156.61, 139.13, 135.00, 128.82, 127.60, 118.01, 112.82, 108.54, 61.13, 55.68, 43.16, 42.89, 42.62, 41.14, 25.84, 23.89. ¹⁹F NMR (376 MHz, CDCl₃) δ -60.40。

The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention Within mind and principle, any modification, equivalent replacement, improvement and so on be should all be included in the protection scope of the present invention.

Claims

1. a kind of trifluoromethyl replaces N- acyl group indolin derivatives, it is characterised in that structural formula is as follows:

2. trifluoromethyl replaces the preparation method of N- acyl group indolin derivatives, characterization step is as follows: by N- acetyl group alkene Propyl aniline, Togni reagent, cuprous iodide, sodium acetate are added heated at constant temperature in reaction tube and are stirred to react, and obtain trifluoromethyl and take For N- acyl group indolin derivatives.

3. trifluoromethyl according to claim 2 replaces the preparation method of N- acyl group indolin derivatives, feature exists It is as follows in the structural formula of the N- acetyl group allyl aniline:

4. trifluoromethyl according to claim 2 replaces the preparation method of N- acyl group indolin derivatives, feature exists In: the solvent is dimethyl sulfoxide, and alkali is sodium acetate, and catalyst is cuprous iodide.

5. trifluoromethyl according to claim 2 replaces the preparation method of N- acyl group indolin derivatives, feature exists In the molar ratio of: the N- acetyl group allyl aniline, Togni reagent, cuprous iodide, sodium acetate be 1:(1-1.5): (0.1- 0.5): (3-6).

6. trifluoromethyl according to claim 2 replaces the preparation method of N- acyl group indolin derivatives, feature exists In reaction temperature is 60-80 DEG C, and the reaction time is 12-24 h.

7. replace the preparation method of N- acyl group indolin derivatives according to the described in any item trifluoromethyls of claim 2-6, It is characterized in that the trifluoromethyl replaces the structure of N- acyl group indolin derivatives as follows: