CN1055923C - Trifluoromethyl dihydrotriazole compound and its synthetic method - Google Patents
Trifluoromethyl dihydrotriazole compound and its synthetic method Download PDFInfo
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- CN1055923C CN1055923C CN95111695A CN95111695A CN1055923C CN 1055923 C CN1055923 C CN 1055923C CN 95111695 A CN95111695 A CN 95111695A CN 95111695 A CN95111695 A CN 95111695A CN 1055923 C CN1055923 C CN 1055923C
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- trifluoromethyl
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Abstract
The present invention relates to a trifluoromethyl dihydrogen triazole compound and a method thereof for synthesizing the triazole compound containing fluorine from the reaction of trifluoromethyl * oxazolone and an activated nitrogen-nitrogen unsaturated bond compound. The synthesizing method comprises: Mannich additional and decarboxylic reaction occurs between the trifluoromethyl * oxazolone and the activated nitrogen-nitrogen unsaturated bond compound in organic solvents under the action of alkali and at room temperature, so that the trifluoromethyl dihydrogen triazole compound is prepared. The method has the advantages of few reaction steps, mild condition, simple and direct operation and high yield. The triazole compound containing fluorine can be developed into new generation agricultural chemicals and medical medicines, and the synthesizing method is also suitable for preparing other organic compounds containing fluorine or nitrogen heterocyclic rings.
Description
The present invention relates to a kind of fluorine-containing nitrogen heterocyclic ring organic compound and synthetic method thereof, specifically be exactly trifluoromethyl dihydrotriazole compound and be the method for the synthetic trifluoromethyl dihydrotriazole compound of raw material with San Fu Jia oxazolones.
The structure of developing from present agricultural chemicals, except a spot of traditional structure, now exploitation (Zhang Yibin that pay attention to fluorochemicals and nitrogen-containing heterocycle compound more, chemistry world, the 36th volume, 5.25.1995), triazole class compounds is as sterilant, insecticidal/acaricidal agent, weedicide and plant-growth regulator, in agriculture production, obtained application more and more widely, key areas (the Shang Ercai etc. of novel pesticide exploitation have also been become, the chemical industry progress 1.11.1995), also has immeasurable influence equally aspect physianthropy.Synthetic and the exploitation of fluorine-containing like this triazole class compounds just has more practical significance and bright prospects, that is to say that trifluoromethyl is introduced triazole class compounds can enlarge insecticidal spectrum.But in present document, do not see the report that pair trifluoromethyl dihydrotriazole compound is arranged.From present synthetic method, normally acid amides becomes triazole compounds with the decarboxylic reaction of amido in addition, trifluoromethylation again, and not only reactions steps is many, complex operation, and also total yield is low, and toxic side effect is big.93 years Tian Weisheng etc. have applied for the process patent (CN92108305.X) of " a kind of method from the synthetic trifluoromethyl pyrpole compounds of three fluorine first oxazolones ", this method is in the presence of alkali, San Fu Jia oxazolones and activatory carbon-to-carbon unsaturated compound at room temperature get the trifluoromethyl pyrpole compounds by Mannich addition and decarboxylic reaction, and this synthetic method responds that step is few, the advantage of mild condition, yield height.We explore a kind of method of synthesizing the trifluoromethyl triazole compounds at the constructional feature of trifluoromethyl dihydrotriazole compound on this basis simple and effectively.
The object of the invention provide a kind of novel trifluoromethyl dihydrotriazole compound and a kind of be the method that raw material synthesizes trifluoromethyl dihydrotriazole compound simple and effectively with three fluorine first oxazolones.
Synthetic method of the present invention is in organic solvent, and San Fu Jia oxazolones and activatory nitrogen-nitrogen unsaturated link(age) compound at room temperature carries out the Mannich addition by the effect of alkali and decarboxylic reaction gets trifluoromethyl dihydrotriazole compound.Reaction is shown below:
Specifically the present invention is that a kind of general formula is
Trifluoromethyl dihydrotriazole compound, when its EWG was ester group, it took off the ester group product and very easily is oxidized to general formula and is
Trifluoromethyl triazole compounds, its synthetic method are to be with molecular formula
San Fu Jia oxazolones and molecular formula activatory nitrogen-nitrogen unsaturated link(age) compound of being EWG-N=N-R be raw material, at ambient temperature, under the effect of organic solvent neutralization bases, react, the preparation general formula is
The method of trifluoromethyl dihydrotriazole compound.Wherein R is methyl, aromatic ring yl or ester group, R
1Be aromatic ring yl, described aromatic ring yl is selected from phenyl or p-methoxy-phenyl, and EWG is ester group, benzoyl, N, N-dimethyl methyl acyl group or H.The mole ratio of described San Fu Jia oxazolones, activatory nitrogen-nitrogen unsaturated link(age) compound and alkali is 1: 1-10: 0.5-2.The mole ratio of recommending is 1: 1-5: 1-1.5.But excessive activatory nitrogen-nitrogen unsaturated link(age) compound and alkali do not influence building-up reactions of the present invention.
Alkali described in the synthetic method of the present invention is organic amine compound, preferably tertiary amine or nitrogen heterocyclic and inorganic hydride with tertiary amine structure, as 1.8-diaza-bicyclo " 5.4.0 " 11-7-alkene, 1.5-diaza-bicyclo " 4.3.0 " ninth of the ten Heavenly Stems-5-alkene, 1.4-diaza-bicyclo " 2.2.2 " octane, 1.4.7-trimethylammonium 1.4.7-7-triazacyclononane, N.N '-Tetramethyl Ethylene Diamine, ethyl diisopropylamine, triethylamine, sodium hydride, N.N-Diethyl Aniline.
Organic solvent described in the synthetic method of the present invention can be toluene, dimethylbenzene, benzene, acetonitrile, methylene dichloride, chloroform, tetrahydrofuran (THF), ether, glycol dimethyl ether, tetracol phenixin.Reaction is to help synthetic method of the present invention in above-mentioned organic solvent, and what of its consumption there is no much influences to reaction, can the solubilizing reaction thing can but not as limit.
In at least 1 hour reaction times of synthetic method of the present invention, be recommended as 1-8 hour.The length in reaction times will influence the yield of the finished product, and the yield of reaction is 45%-90%.
The present invention compares with existing patent with existing technology, will enlarge insecticidal spectrum because trifluoromethyl is introduced triazole class compounds, and this trifluoromethyl triazole compounds can be developed into agricultural chemicals of new generation and medical drugs.Its synthetic method has possessed that reactions steps is few, mild condition, easy and simple to handle and characteristics that yield is high, make it agricultural chemicals and medical aspect applicating and exploitation more have practical value and bright prospects.
Following embodiment will help to understand the present invention, but be not limited to the present invention.
Embodiment 12,5-phenylbenzene-3-Trifluoromethyl-1,2-dihydro triazole-carboxylic acid, ethyl ester (2a) dissolving trifluoromethyl oxazolone (275mg, 1.2mmol.), (203mg 1.2mmol.) in the 2ml methylene dichloride, drips 1 to the phenylazo carboxylic acid, ethyl ester, 8-diazabicyclo [5,4,0] 11-7-alkene (0.18ml, 1.2mmol).At room temperature, the reaction mixture stirring reaction is 4 hours.Decompression is removed reaction solvent and must be reacted thick product.Separation obtains 2,5-phenylbenzene-3-Trifluoromethyl-1,2-dihydro triazole-carboxylic acid, ethyl ester through silica gel column chromatography for it.Colourless crystallization.313mg, yield 72%.Analytical data is as described below.M.p.88-88.5 ℃ of IR ν: 1740 (C=O); 1630 (C=N) cm
-1 1H-NMR δ: 7.9-8.0 (2H, m, Ar-H), 7.3-7.6 (5H, m, Ar-H), 7.1-7.2 (3H, m, Ar-H), 5.1 (1H, q, C5-H), 4.0-4.3 (2H, m, OCH
2CH
3), 1.1 (3H, t, OCH
2CH
3) ppm.
19F-NMR (CH
2Cl
2) δ: 2.1 (s, CF
3) ppmMS m/e:364 (M+1), 363 (M
+), 294 (M+1-HF), 290 (M-CO
2C
2H
5) .C
18H
16F
3N
3O
2Calculated value: C 59.50, H 4.44, and N 11.56
Measured value: C 59.46, H 4.23, and N 11.72
Embodiment 2 implementation conditions are as described in the embodiment 1, difference and the results are shown in Table 1.3-trifluoromethyl-5-phenyl-1,2-dihydro triazole-1, m.p.86-87 ℃ of 2-ethyl dicarboxylate (2b).IR(film)ν：1750(C＝O)，1630(C＝N)cm
-1。
1H-NMR δ: 7.9 (2H, m, Ar-H), 7.5 (1H, m, Ar-H), 7.4 (2H, m, Ar-H), 6.1 (1H, q, J=5.3Hz, C5-H), 4.2-4.4 (4H, m, 2X OCH
2CH
3), 1.4 (3H, t, OCH
2CH
3), 1.1 (3H, t, J=7.1Hz, OCH
2CH
3) ppm.MS m/e:360 (M+1), 218 (M-CO
2CH
2CH
3); 174,146.C
15H
16F
3N
3O
4Calculated value: C 50.14, H 4.49, and N 11.69
Measured value: C 49.98, H 4.19, and N 11.721,2-dibenzoyl-3-trifluoromethyl-5-phenyl-1, m.p.145 ℃ of IR of 2-dihydro triazole (2c) (film) ν: 1690 (C=O), 1660 (C=N) cm
-1.
1H-NMR δ: 8.1-8.3 (2H, m, Ar-H), 7.0-7.7 (13H, m, Ar-H), 6.0 (1H, q, J=5Hz, C5-H) ppm.
19F-NMR δ: 0.5ppm (d, J=4Hz, CF
3) .MS m/e:423 (M
+), 354,105.C
23H
16F
3N
3O
2Calculated value: C 65.24, H 3.81, and N 9.92
Measured value: C 65.65, H 3.69, and N 9.861,2-dibenzoyl-3-trifluoromethyl-5-p-methoxy-phenyl-1, m.p.174 ℃ of IR of 2-dihydro triazole (2d) (film) ν: 1710 (C=O), 1610 (C=N) cm
-1.
1H-NMR δ: 6.9-8.1 (14H, m, Ar-H); , 5.7 (1H, q, J=5Hz, C5-H), 3.9 (3H, s, OCH3) ppm.
19F-NMR (CH
2Cl
2) δ :-1 (s, CF
3) ppm.MS m/e:453 (M
+), 384,105 (PhCO) .C
24H
18F
3N
3O
3Calculated value: C 63.57, H 4.00, and N 9.27
Measured value: C 63.70, H 3.86, N 9.22N, N-dimethyl-2,5-phenylbenzene-3-Trifluoromethyl-1, m.p.130-132 ℃ of IR of 2-dihydro triazole methane amide (2e) (film) ν: 1700 (C=O), 1640 (C=N) cm
-1.
1H-NMR δ: 8.0-8.4 (2H, m, Ar-H), 7.4-7 .8 (8H, m, Ar-H), 5.3-5.6 (1H, q, J=5Hz, C5-H), 3.0 (6H, s, N (CH)
3)
2) ppm.
19F-NMR (CCl
4) δ: 0 (d, J=6Hz, CF
3) ppm.MS m/e:363 (M+1), 362 (M
+), 293,72 (Me
2NCO, 100) .C
18H
17F
3N
4O calculated value: C 59.66, H 4.73, N 15.46.
Measured value: C 59.68, H 4.73, N 15.64. embodiment 32,5-phenylbenzene-3-Trifluoromethyl-1,2-dihydro triazole (3a) dissolving 80mg 2,5-phenylbenzene-3-Trifluoromethyl-1,2-dihydro triazole-carboxylic acid, ethyl ester (2a) is in the 1ml tetrahydrofuran (THF).After adding 0.2ml 85% hydrazine hydrate, back flow reaction 6 hours.The reaction solution ether extraction.Extracting solution is after washing, drying, and removal of solvent under reduced pressure must be reacted thick product.Separation obtains 69mg 2,5-phenylbenzene-3-Trifluoromethyl-1,2-dihydro triazole (3a), colourless crystallization through silica gel column chromatography for it.Yield 95%.Analytical data is as described below.M.p.186 ℃, decompose.
1H-NMR (acetone-d
6) δ: 7.2-8.0 (10H, m, Ar-H), 6.7-7.1 (1H, brs, NH); 5.9-6.2 (1H, q, J=5Hz, C3-H) ppm.
19F-NMR δ: 4.5ppm (d, J=3Hz, CF
3) ppm.MS:291 (M
+), 222 (M-CF
3, 100) and .C
15H
12F
3N
3Calculated value: C 61.83, H 4.15, and N 14.43
Measured value: C 61.80, H 4.15, and N 14.28 dissolving 4a obtain 2,5-phenylbenzene-3-trifluoromethyl triazole (4a) through atmospheric oxidation in chloroform.Yield 98%.M.p.69-70 ℃
1H-NMR δ: 8.2 (2H, m, Ar-H), 7.6 (5H, s, Ar-H), 7.4 (3H, m, Ar-H) ppm.
19F-NMR:-15 (s, CF
3) ppmMS m/e:290 (M+1), 289 (M
+), 194,91 (C
7H
7) .C
15H
10F
3N
3Calculated value: C 62.27, H 3.49, N 14.53.
Measured value: C 62.18, H 3.47, and N 14.50
Table 1entry Ar R EWG solvent time (hr yield (
s) ％)a Ph CO
2Et CO
2Et CH
2Cl
2 10 56b Ph Ph CO
2Et CH
2Cl
2 4 72c Ph PhCO PhCO CH
2Cl
2 1 55d Ph Ph Me
2NCO toluene 5 70e p-CH
3OPh PhCO PhCO CH
2Cl
2 1 62f p-CH
3OPh CO
2Et CO
2Et CH
2Cl
2 4 60
Claims (6)
1. a trifluoromethyl dihydrotriazole compound is characterized in that general formula is
Wherein R is methyl, aromatic ring yl or ester group; R
1Be aromatic ring yl, described aromatic ring yl is selected from phenyl or p-methoxy-phenyl; EWG is ester group, benzoyl, N, N-dimethyl methyl acyl group or H.
2. one kind from molecular formula is
The directly synthetic general formula of San Fu Jia oxazolones be
The trifluoromethyl dihydrotriazole compound method, it is characterized in that at ambient temperature with organic solvent in, San Fu Jia oxazolones and molecular formula are that EWG-N=N-R activatory nitrogen-nitrogen unsaturated link(age) compound carries out building-up reactions under the effect of alkali, and wherein R is methyl, aromatic ring yl or ester group, R
1Be aromatic ring yl, described aromatic ring yl is selected from phenyl or p-methoxy-phenyl, and EWG is ester group, benzoyl, N, N-dimethyl methyl acyl group or H; The mole ratio of described San Fu Jia oxazolones, activatory nitrogen-nitrogen unsaturated link(age) compound and alkali is 1: 1-10: 0.5-2.
3. the method for a synthetic trifluoromethyl dihydrotriazole compound as claimed in claim 2 is characterized in that the mole ratio of described three fluorine first oxazolones, activatory nitrogen-nitrogen unsaturated link(age) compound and alkali is 1: 1-5: 1-1.5.
4. method as claim 2 or 3 described synthetic trifluoromethyl triazole dihydro-compounds, it is characterized in that described alkali be 1.8-diaza-bicyclo " 5.4.0 " 11-7-alkene, 1.5-diaza-bicyclo " 4.3.0 " ninth of the ten Heavenly Stems-5-alkene, 1.4-diaza-bicyclo " 2.2.2 " octane, 1.4.7-trimethylammonium 1.4.7-7-triazacyclononane, N.N '-Tetramethyl Ethylene Diamine, ethyl diisopropylamine, triethylamine, sodium hydride, N.N-Diethyl Aniline.
5. the method as claim 2 or 3 described synthetic trifluoromethyl dihydrotriazole compounds is characterized in that described organic solvent is toluene, dimethylbenzene, benzene, acetonitrile, methylene dichloride, chloroform, tetrahydrofuran (THF), ether, glycol dimethyl ether, tetracol phenixin.
6. the purposes of a trifluoromethyl dihydrotriazole compound is characterized in that when the EWG of trifluoromethyl dihydrotriazole compound group is ester group, can be used for preparing general formula and is
The trifluoromethyl triazole compounds.
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| CN1055923C true CN1055923C (en) | 2000-08-30 |
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| CN101973829B (en) * | 2010-09-02 | 2013-06-19 | 中国科学院上海有机化学研究所 | Trifluoromethylation of trifluoromethyl aryl sulfonium salt to heterocyclic compound under metal trigger |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN88101620A (en) * | 1987-03-27 | 1988-10-19 | 科米阿衣化学工业株式会社 | phenyl triazole derivatives and insecticides |
| CN1079221A (en) * | 1992-05-29 | 1993-12-08 | 组合化学工业株式会社 | New triazole derivative and sterilant and miticide |
| CN1105179A (en) * | 1993-04-16 | 1995-07-12 | 组合化学工业株式会社 | Triazole derivative, insecticidal/acaricidal agent, and process for producing the same |
-
1995
- 1995-07-17 CN CN95111695A patent/CN1055923C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN88101620A (en) * | 1987-03-27 | 1988-10-19 | 科米阿衣化学工业株式会社 | phenyl triazole derivatives and insecticides |
| CN1079221A (en) * | 1992-05-29 | 1993-12-08 | 组合化学工业株式会社 | New triazole derivative and sterilant and miticide |
| CN1105179A (en) * | 1993-04-16 | 1995-07-12 | 组合化学工业株式会社 | Triazole derivative, insecticidal/acaricidal agent, and process for producing the same |
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