CN1760187A - Method for preparing Tebucomazole in high purity - Google Patents
Method for preparing Tebucomazole in high purity Download PDFInfo
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- CN1760187A CN1760187A CN 200510032349 CN200510032349A CN1760187A CN 1760187 A CN1760187 A CN 1760187A CN 200510032349 CN200510032349 CN 200510032349 CN 200510032349 A CN200510032349 A CN 200510032349A CN 1760187 A CN1760187 A CN 1760187A
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- tebucomazole
- high purity
- consumption
- tertiary butyl
- oxyethane
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Abstract
A process for preparing high-purity pentazolol features the reaction between 1-(4-chlorphenylethyl)-1-tert-butyl-1, 2-epoxy ethane and 1,2,4-triazole in organic polar solvent under existence of alkali while adding catalyst chosen from N,N-dimethyl-4-aminopyridine, N,N-dimethylphenylamine, methylphrrolidone, dimethyl formamide, methanol sodium, ethanol sodium, potassium hydroxide and sodium hydroxide. Its advantages are high output rate and high purity.
Description
Technical field
The present invention relates to the synthetic method of a kind of agricultural chemicals tebuconazole (4,4-dimethyl-3-(1H-1,2,4-triazol-1-yl methyl)-1-(4-chloro-phenyl-)-3-amylalcohol).
Background technology
Tebuconazole (4,4-dimethyl-3-(1H-1,2,4-triazol-1-yl methyl)-and 1-(4-chloro-phenyl-)-3-amylalcohol, 1), be the triazole species low toxicity efficient germicide of German Bayer AG exploitation, be sterol demethylation inhibitor, be used for seed treatment or the foliage spray of important cash crop.Its structural formula is:
Major impurity is the isomer by product that generates in the ring-opening reaction in the synthetic tebuconazole---4,4-dimethyl-3-(4H-1,2,4-triazole-4-ylmethyl)-1-(4-chloro-phenyl-)-3-amylalcohol (2), because 2 and 1 character is close, not easily separated, cause product purity to have only 95%, yield is lower than 76% (with 1-(4-chlorobenzene ethyl)-1-tertiary butyl-1,2-oxyethane, 3).Because 1,2,1-bit substituent derivative just has fungicidal activity in the 4-triazole class compounds, 4-bit substituent derivative does not have fungicidal activity.Therefore in synthetic tebuconazole process, should control the generation of the different tebuconazole of 4-bit substituent derivative, not only can save the product purification operation, and improve yield and quality product, reduce production costs.
Summary of the invention
Technical problem to be solved by this invention is the defective that overcomes above-mentioned prior art, and a kind of product purity height, yield height, the low unit operation preparation method of Tebucomazole in high purity simply and easily that reaches of cost are provided.
Technical conceive of the present invention is such:
1,2, the 4-triazole has two kinds of isomer 1H-1, and 2,4-triazole (4), 4H-1,2,4-triazole (5) is in the running balance:
Wherein 4 is more stable, is main isomer.4 and 3 reactions generate principal product 1.5 and 3 less reactions of content generate impurity 2, and content is few.Utilize 1,2, the difference of two kinds of isomer stability of 4-triazole selects to have the catalyzer of fine selectivity, is converted into 4 with 5 effectively in reaction system, and what will may generate when not using catalyzer 2 is converted into 1.May command production like this makes w in the reaction solution (2)＜0.5% (liquid chromatography, area normalization), does not need the recrystallization product purity to reach w (1) 〉=98.0% (liquid chromatography, external standard), yield 〉=80.0% (in 3)).
Technical scheme of the present invention: with 1-(4-chlorobenzene ethyl)-1-tertiary butyl-1,2-oxyethane is raw material, in the polar organic solvent that alkali exists with 1,2, the reaction of 4-triazole, add catalyzer during reaction, described catalyzer is N, N-dimethyl-4-aminopyridine, N, accelerine, methyl-2-pyrrolidone, dimethyl formamide, sodium methylate, sodium ethylate, potassium hydroxide, in the sodium hydroxide any, catalyst levels are 1-(4-chlorobenzene ethyl)-1-tertiary butyl-1,0.1～5.0% of 2-oxyethane consumption, temperature of reaction is 90～150 ℃, and the reaction times is 4～12h, obtains Tebucomazole in high purity.
Reaction formula is as follows:
Described 1,2,4-triazole consumption is 1-(4-chlorobenzene ethyl)-1-tertiary butyl-1, the 30.0-50.0% of 2-oxyethane consumption.
Alkali can be in potassium hydroxide, sodium hydroxide, lithium hydroxide, salt of wormwood, yellow soda ash, sodium methylate, the sodium ethylate etc. any, and the alkali consumption is 1-(4-chlorobenzene ethyl)-1-tertiary butyl-1,1.0～10.0% of 2-oxyethane consumption.
Polar organic solvent can be in Fatty Alcohol(C12-C14 and C12-C18), pimelinketone, ethyl acetate, the dimethyl formamide etc. any, and the polar organic solvent consumption is 1-(4-chlorobenzene ethyl)-1-tertiary butyl-1,50.0～200.0% of 2-oxyethane consumption.
1-(4-the chlorobenzene ethyl)-1-tertiary butyl-1,2-oxyethane are 1-(4-chloro-phenyl-)-4, the epoxidation product of 4-dimethyl-propione.
Compare with other synthetic methods, the present invention has the following advantages:
1) product purity height, w (1) 〉=98.0% (liquid chromatography, external standard);
2) yield height, yield 〉=80.0% (in 3);
3) do not need recrystallization, easy to operate.
Embodiment
Below in conjunction with embodiment the present invention is described in detail further.
Prior art embodiment: do not add the synthetic method of the prior art under the situation of catalyzer, this example is used for contrasting with the present invention.
120g (0.40mol) 3, potassium hydroxide 3g (0.05mol), 1,2,4-triazole 40g (0.55mol), propyl carbinol 100mL add the 500mL there-necked flask that has stirring and return line, and reflux temperature stirs 6h down for 120 ℃, and reaction is finished, add hydrochloric acid neutralization, phase-splitting, organic phase crystallisation by cooling, filtration drying get white solid 105g, w (1) 〉=88.0% (liquid chromatography, external standard), yield 〉=75.1% (in 3).The synthetic product is carried out the separating for several times purification obtain 5g white crystal 2,182～183 ℃ of fusing points.Obtain 89g white crystal 1, w (1) 〉=95.0% (liquid chromatography, external standard), 102～104 ℃ of (document [5] values: 102～104 ℃ of fusing points) of fusing point.
The spectral data of different tebuconazole 2 is as follows: ESI-MS (m/z): 308 (M
+).
1H NMR (400M Hz, CDCl
3), δ: 1.03 (s, 9H, C (CH
3)
3), 1.64 (tt, J=14.0Hz, 4.0Hz, 1H, CH
2), 1.87 (m, 2H, CH
2CH
2), 2.20 (s, 1H, OH), 2.36 (tt, J=14.0Hz, 4.0Hz, 1H, CH
2C
6H
4Cl), 4.11 (d, J=14.0Hz, 1H, CH
2), 4.24 (d, J=14.0Hz, 1H, CH
2), 6.92 (d, J=8.8Hz, 2H, phenyl ring 2,6-H), 7.18 (d, J=8.0Hz, 2H, phenyl ring 3,5-H), 8.37 (s, 2H, 4H-1,2,4-triazole ring 3,5-H).
13C NMR (400MHz, CDCl
3), δ: 25.38 (3C, 3 * CH
3), 30.10 (1C, CH
2), 36.37 (1C, CH
2), 38.45 (1C, C), 51.06 (1C, CH
2), 65.90 (1C, C-OH), 128.68 (2C, phenyl ring 3,5-C), 129.49 (2C, phenyl ring 2,6-C), 132.20,139.86 (2C, phenyl ring 1,4-C), 144.23 (2C, 4H-1,2,4-triazole ring 3 5-C), meets constitutional features.
The embodiment of the invention 1
120g (0.40mol) 3, potassium hydroxide 3g (0.05mol), 1,2,4-triazole 40g (0.55mol), N, N-dimethyl-4-aminopyridine 1g, propyl carbinol 100mL add the 500mL there-necked flask that has stirring and return line, reflux temperature stirs 6h down for 120 ℃, reaction is finished, and adds hydrochloric acid neutralization, phase-splitting, the organic phase crystallisation by cooling, filtration drying gets white solid 102g, w (1) 〉=98.0% (liquid chromatography, external standard), yield 〉=81.4% (in 3).102～104 ℃ of (literature values: 102～104 ℃ of fusing points) of fusing point.
The following ESI-MS of the spectral data of tebuconazole 1 (m/z): 308 (M
+).
1H NMR (400MHz, CDCl
3), δ: 1.03 (s, 9H, C (CH
3)
3), 1.67 (tt, J=14.0Hz, 4.0Hz, 1H, CH
2), 1.82 (m, 2H, CH
2CH
2), 2.44 (tt, J=14.0Hz, 4.0Hz, 1H, CH
2), 3.01 (s, 1H, OH), 4.33 (d, J=14.4Hz, 1H, CH
2), 4.38 (d, J=14.4Hz, 1H, CH
2), 6.95 (d, J=8.4Hz, 2H, phenyl ring 2,6-H), 7.23 (d, J=8.4Hz, 2H, phenyl ring 3,5-H), and 8.02 (s, 1H, 1H-1,2,4-triazole ring 5-H), 8.25 (s, 1H, 1H-1,2,4-triazole ring 3-H) meet constitutional features.
The embodiment of the invention 2
120g (0.40mol) 3, potassium hydroxide 6g (0.10mol), 1,2,4-triazole 40g (0.55mol), N, accelerine 1g, dimethyl formamide 100mL add the 500mL there-necked flask that has stirring and return line, 130 ℃ are stirred 4h down, reaction is finished, and adds hydrochloric acid neutralization, secondary distillating recovering solvent, the organic phase crystallisation by cooling of pressing, the dry white solid 106g that gets of washing filtering, w (1) 〉=98.6% (liquid chromatography, external standard), yield 〉=85.0% (in 3).
The embodiment of the invention 3
120g (0.40mol) 3, sodium ethylate 7g (0.10mol), 1,2,4-triazole 40g (0.55mol), N, N-dimethyl-4-aminopyridine 0.5g, propyl carbinol 100mL add the 500mL there-necked flask that has stirring and return line, 120 ℃ are stirred 6h down, reaction is finished, and adds hydrochloric acid neutralization, secondary distillating recovering solvent, the organic phase crystallisation by cooling of pressing, filtration drying gets white solid 101g, w (1) 〉=98.3% (liquid chromatography, external standard), yield 〉=80.7% (in 3).
The embodiment of the invention 4
120g (0.40mol) 3, sodium ethylate 7g (0.10mol), 1,2,4-triazole 40g (0.55mol), N, N-dimethyl-4-aminopyridine 0.5g, pimelinketone 100mL add the 500mL there-necked flask that has stirring and return line, 130 ℃ are stirred 4h down, reaction is finished, and adds hydrochloric acid neutralization, secondary distillating recovering solvent, the organic phase crystallisation by cooling of pressing, the dry white solid 100g that gets of washing filtering, w (1) 〉=98.9% (liquid chromatography, external standard), yield 〉=80.4% (in 3).
Claims (5)
1, a kind of preparation method of Tebucomazole in high purity, with 1-(4-chlorobenzene ethyl)-1-tertiary butyl-1,2-oxyethane is raw material, in the polar organic solvent that alkali exists with 1,2, the reaction of 4-triazole, it is characterized in that: add catalyzer during reaction, described catalyzer is N, N-dimethyl-4-aminopyridine, N, accelerine, methyl-2-pyrrolidone, dimethyl formamide, sodium methylate, sodium ethylate, potassium hydroxide, in the sodium hydroxide any, catalyst levels is 1-(4-chlorobenzene ethyl)-1-tertiary butyl-1, the 0.1-5.0% of 2-oxyethane consumption, and temperature of reaction is 90-150 ℃, reaction times is 4-12h, obtains Tebucomazole in high purity.
2, the preparation method of Tebucomazole in high purity according to claim 1 is characterized in that 1,2, and 4-triazole consumption is 1-(4-chlorobenzene ethyl)-1-tertiary butyl-1, the 30.0-50.0% of 2-oxyethane consumption.
3, the preparation method of Tebucomazole in high purity according to claim 1, it is characterized in that alkali is any in potassium hydroxide, sodium hydroxide, lithium hydroxide, salt of wormwood, yellow soda ash, sodium methylate, the sodium ethylate, the alkali consumption is 1-(4-chlorobenzene ethyl)-1-tertiary butyl-1, the 1.0-10.0% of 2-oxyethane consumption.
4, the preparation method of Tebucomazole in high purity according to claim 1, it is characterized in that polar organic solvent is any in Fatty Alcohol(C12-C14 and C12-C18), pimelinketone, ethyl acetate, the dimethyl formamide, the polar organic solvent consumption is 1-(4-chlorobenzene ethyl)-1-tertiary butyl-1, the 50.0-200.0% of 2-oxyethane consumption.
5, the preparation method of Tebucomazole in high purity according to claim 1 is characterized in that 1-(4-chlorobenzene ethyl)-1-tertiary butyl-1, and 2-oxyethane is 1-(4-chloro-phenyl-)-4, the epoxidation product of 4-dimethyl-propione.
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| CN100336810C CN100336810C (en) | 2007-09-12 |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102276541A (en) * | 2010-06-11 | 2011-12-14 | 南通派斯第农药化工有限公司 | Preparation method of 1-(4-chlorophenyl)-3-(1-H-1,2,4-triazolyl-1-methyl)-4,4-dimethyl pentan-3-ol |
| CN102382068A (en) * | 2011-08-09 | 2012-03-21 | 湖南大学 | Method for preparing 1-(1, 2, 4-triazole-1-yl)-2-aryl-2-alkanol |
| CN102442958A (en) * | 2010-10-25 | 2012-05-09 | 南通派斯第农药化工有限公司 | Preparation method of isomer-removed tebuconazole |
| CN103435564A (en) * | 2013-08-22 | 2013-12-11 | 上虞颖泰精细化工有限公司 | Preparation method of tebuconazole |
| CN105820128A (en) * | 2015-01-05 | 2016-08-03 | 湖南大学 | Preparation method of cyproconazole |
| CN108299319A (en) * | 2018-02-08 | 2018-07-20 | 盐城辉煌化工有限公司 | The easy technique new method of synthesis in water Tebuconazole |
| CN111406046A (en) * | 2017-11-17 | 2020-07-10 | 华东理工大学 | Polymorphic form of tebuconazole and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US429735A (en) * | 1890-06-10 | Multiplex telegraphy | ||
| DE3237400A1 (en) * | 1982-10-08 | 1984-04-12 | Bayer Ag, 5090 Leverkusen | SUBSTITUTED 1-HYDROXYETHYL-TRIAZOLYL DERIVATIVES |
-
2005
- 2005-11-08 CN CNB2005100323494A patent/CN100336810C/en not_active Expired - Fee Related
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102276541B (en) * | 2010-06-11 | 2013-12-11 | 南通派斯第农药化工有限公司 | Preparation method of 1-(4-chlorophenyl)-3-(1-H-1,2,4-triazolyl-1-methyl)-4,4-dimethyl pentan-3-ol |
| CN102276541A (en) * | 2010-06-11 | 2011-12-14 | 南通派斯第农药化工有限公司 | Preparation method of 1-(4-chlorophenyl)-3-(1-H-1,2,4-triazolyl-1-methyl)-4,4-dimethyl pentan-3-ol |
| CN102442958B (en) * | 2010-10-25 | 2015-02-18 | 南通派斯第农药化工有限公司 | Preparation method of isomer-removed tebuconazole |
| CN102442958A (en) * | 2010-10-25 | 2012-05-09 | 南通派斯第农药化工有限公司 | Preparation method of isomer-removed tebuconazole |
| CN102382068B (en) * | 2011-08-09 | 2013-11-27 | 湖南大学 | Method for preparing 1-(1, 2, 4-triazole-1-yl)-2-aryl-2-alkanol |
| CN102382068A (en) * | 2011-08-09 | 2012-03-21 | 湖南大学 | Method for preparing 1-(1, 2, 4-triazole-1-yl)-2-aryl-2-alkanol |
| CN103435564A (en) * | 2013-08-22 | 2013-12-11 | 上虞颖泰精细化工有限公司 | Preparation method of tebuconazole |
| CN103435564B (en) * | 2013-08-22 | 2015-09-02 | 上虞颖泰精细化工有限公司 | A kind of preparation method of tebuconazole |
| CN105820128A (en) * | 2015-01-05 | 2016-08-03 | 湖南大学 | Preparation method of cyproconazole |
| CN105820128B (en) * | 2015-01-05 | 2018-01-19 | 江西华士药业有限公司 | A kind of preparation method of cyproconazole |
| CN111406046A (en) * | 2017-11-17 | 2020-07-10 | 华东理工大学 | Polymorphic form of tebuconazole and preparation method thereof |
| CN111406046B (en) * | 2017-11-17 | 2022-12-23 | 华东理工大学 | Polymorphic form of tebuconazole and preparation method thereof |
| CN108299319A (en) * | 2018-02-08 | 2018-07-20 | 盐城辉煌化工有限公司 | The easy technique new method of synthesis in water Tebuconazole |
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|---|---|
| CN100336810C (en) | 2007-09-12 |
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