CN109574904A - A kind of trifluoromethyl substituted-dihydro Benzazole compounds and preparation method thereof - Google Patents
A kind of trifluoromethyl substituted-dihydro Benzazole compounds and preparation method thereof Download PDFInfo
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- CN109574904A CN109574904A CN201811098064.4A CN201811098064A CN109574904A CN 109574904 A CN109574904 A CN 109574904A CN 201811098064 A CN201811098064 A CN 201811098064A CN 109574904 A CN109574904 A CN 109574904A
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- trifluoromethyl
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- trifluoromethyl substituted
- indole derivatives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
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Abstract
The invention discloses a kind of trifluoromethyl substituted-dihydro Benzazole compounds and preparation method thereof; use the silver nitrate of catalytic amount; using fluoroform sulfinic acid sodium and N- acetyl group allyl aniline as reactant; acetonitrile and water are as mixed solvent; temperature is controlled at 40-60 DEG C, reacts 12-24h through the isolated trifluoromethyl substituted-dihydro Benzazole compounds of column chromatographic analysis.The present invention provides a kind of new method that trifluoromethyl substituted-dihydro Benzazole compounds are synthesized using acyl group allyl aniline and fluoroform sulfinic acid sodium 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
Technical field
The present invention relates to the field of chemical synthesis, and in particular to a kind of system of trifluoromethyl substituted-dihydro Benzazole compounds
It is standby.
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 a kind of dihydros
The preparation method of indole fluoroform base derivative provides a kind of mild, cheap method synthesizing dihydro indole fluoroform base
Derivative.The synthesising method reacting condition is mild, opens wide system operation, handy and safe, raw material in air under the conditions of 40-60 DEG C
It is cheap and easy to get with catalyst, it is a kind of environmental-friendly synthetic method.
It realizes the technical scheme is that a kind of trifluoromethyl substituted-dihydro benzazolyl compounds (II), structure is as follows:
,
Wherein, R1For fluorine, chlorine, bromine, iodine, methyl, methoxyl group, trifluoromethyl, ethyl, isopropyl, tert-butyl；R2For hydrogen, methyl.
The preparation method of the trifluoromethyl substituted-dihydro indole derivatives (II), steps are as follows: by N- acetyl group allyl
Base aniline, Sodium trifluoromethanesulfinate, silver nitrate, potassium peroxydisulfate are added heated at constant temperature in reaction tube and are stirred to react, and obtain trifluoro
Methyl substituted-dihydro indole derivatives (II).
The structure of the N- acetyl group allyl aniline (I) is as follows:
Wherein, R1For fluorine, chlorine, bromine, iodine, methyl, methoxyl group, trifluoromethyl, ethyl, isopropyl, tert-butyl；R2For hydrogen, methyl.
The solvent is the mixed solvent of acetonitrile and water, and oxidant is potassium peroxydisulfate, and catalyst is silver nitrate and hexafluoro antimony
Any one in sour silver.
The N- acetyl group allyl aniline, fluoroform sulfinic acid sodium, silver, potassium peroxydisulfate molar ratio be 1:(1-
1.5): 0.1:4.
The reaction temperature is 40-60 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 a kind of preparation method of trifluoromethyl substituted-dihydro indole derivatives,
The method directly carries out in air, efficiently synthesizes product trifluoromethyl substituted-dihydro indoles using raw material cheap and easy to get.
It is easy to operate and safe involved in this method, have the advantages that reaction condition mild, be good economy performance, environmental-friendly.
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
The preparation method of trifluoromethyl substituted-dihydro indole derivatives, steps are as follows:
N- acetyl group allyl aniline (0.5 mmol) is added in 10 mL reaction tubes, fluoroform sulfinic acid sodium (0.5
Mmol), silver nitrate (0.05 mmol), potassium peroxydisulfate (2 mmol) stir 12 hours at 40 DEG C, and column chromatography silica gel separates
To final product, be 100 % by N- acetyl group allyl aniline moles in terms of, 63 % 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
The preparation method of trifluoromethyl substituted-dihydro indole derivatives, steps are as follows:
The fluoro- N- acetyl group allyl aniline of 4- (0.5 mmol) is added in 10 mL reaction tubes, fluoroform sulfinic acid sodium
(0.75 mmol), silver hexafluoroantimonate (0.05 mmol), potassium peroxydisulfate (2 mmol) stir 24 hours at 50 DEG C, column chromatography
The isolated final product of silica gel, by N- acetyl group allyl aniline moles be 100 % in terms of, 53 % 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
The preparation method of trifluoromethyl substituted-dihydro indole derivatives, steps are as follows:
4- methoxyl group N- acetyl group allyl aniline (0.5 mmol) is added in 10 mL reaction tubes, fluoroform sulfinic acid sodium
(0.6 mmol), silver nitrate (0.05 mmol), potassium peroxydisulfate (2 mmol) stir 12 hours at 60 DEG C, column chromatography silica gel point
From obtaining final product, be 100 % by N- acetyl group allyl aniline moles in terms of, 43 % 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, it is all in spirit of the invention and
Within principle, any modification, equivalent replacement, improvement and so on be should all be included in the protection scope of the present invention.
Claims (7)
1. a kind of trifluoromethyl substituted-dihydro indole derivatives, it is characterised in that structural formula is as follows:
,
Wherein, R1For fluorine, chlorine, bromine, iodine, methyl, methoxyl group, trifluoromethyl, ethyl, isopropyl, tert-butyl；R2For hydrogen, methyl.
2. the preparation method of trifluoromethyl substituted-dihydro indole derivatives, characterization step are as follows: by N- acetyl group allyl benzene
Heating stirring reaction in reaction tube is added in amine, Sodium trifluoromethanesulfinate, silver nitrate, potassium peroxydisulfate, obtains trifluoromethyl substitution
Indolin derivatives.
3. the preparation method of trifluoromethyl substituted-dihydro indole derivatives according to claim 2, it is characterised in that described
The structural formula of N- acetyl group allyl aniline is as follows:
Wherein, R1For fluorine, chlorine, bromine, iodine, methyl, methoxyl group, trifluoromethyl, ethyl, isopropyl, tert-butyl；R2For hydrogen, methyl.
4. the preparation method of trifluoromethyl substituted-dihydro indole derivatives according to claim 2, it is characterised in that: described
Solvent is the mixed solvent of acetonitrile and water, and oxidant is potassium peroxydisulfate, and catalyst is any in silver nitrate and silver hexafluoroantimonate
It is a kind of.
5. the preparation method of trifluoromethyl substituted-dihydro indole derivatives according to claim 2, it is characterised in that: described
N- acetyl group allyl aniline, fluoroform sulfinic acid sodium, silver nitrate, potassium peroxydisulfate molar ratio be 1:(1-1.5): 0.1:4.
6. the preparation method of trifluoromethyl substituted-dihydro indole derivatives according to claim 2, which is characterized in that reaction
Temperature is 40-60 DEG C, and the reaction time is 12-24 h.
7. according to the preparation method of the described in any item trifluoromethyl substituted-dihydro indole derivatives of claim 2-6, feature
It is that the structure of the trifluoromethyl substituted-dihydro indole derivatives is as follows:
Wherein, R1For fluorine, chlorine, bromine, iodine, methyl, methoxyl group, trifluoromethyl, ethyl, isopropyl, tert-butyl；R2For hydrogen, methyl.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111100058A (en) * | 2019-11-22 | 2020-05-05 | 华东师范大学 | 3, 3-dicarboxylic ester-indoline-2-thioketone compound and synthesis method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104402793A (en) * | 2014-11-04 | 2015-03-11 | 华东师范大学 | 3-substituted oxindole derivatives, and synthetic method and application thereof |
-
2018
- 2018-09-20 CN CN201811098064.4A patent/CN109574904A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104402793A (en) * | 2014-11-04 | 2015-03-11 | 华东师范大学 | 3-substituted oxindole derivatives, and synthetic method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| DEQIANG LIANG ET AL.: "Synthesis of CF3CH2‑Containing Indolines by Transition-Metal-Free Aryltrifluoromethylation of Unactivated Alkenes", 《J.ORG.CHEM.》 * |
| JUNCHAO WANG ET AL.: "An External-Catalyst-Free Trifluoromethylation/Cyclization Strategy To Access Trifluoromethylated-Dihydroisoquinolinones/Indolines with Togni Reagent II", 《ORG.LETT.》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111100058A (en) * | 2019-11-22 | 2020-05-05 | 华东师范大学 | 3, 3-dicarboxylic ester-indoline-2-thioketone compound and synthesis method and application thereof |
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