CN1803802A - Method for synthesizing oxazole pyridone compound - Google Patents
Method for synthesizing oxazole pyridone compound Download PDFInfo
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- CN1803802A CN1803802A CN 200510006909 CN200510006909A CN1803802A CN 1803802 A CN1803802 A CN 1803802A CN 200510006909 CN200510006909 CN 200510006909 CN 200510006909 A CN200510006909 A CN 200510006909A CN 1803802 A CN1803802 A CN 1803802A
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- pyridine
- oxazole
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Abstract
The synthesis method for thiazolopyridinone in organic chemical field comprises: using bitrichloromethyl carbonate and o-aminohydroxypyridine with mole ratio of 0.3-0.7 as materials; the thedichloromethane, dichloroethane, trichloromethane, tetrachloromethane, chlorobenzene, benzene, toluene, xylene, and THF as solvent by weight ratio with former carbonate as 1-10; the pyridine, DMF, and triethylamine as initiator by mole ratio with the carbonate as 0.001-1; the pyridine, DMF, triethylamine, hydroxide or carbonate or bicarbonate of alkali metal or alkaline-earth metal as bound acid agent by mole ratio with the carbonate as 6-10; then, stirring to react for 0.5-5h at 0-100Deg. This invention has high yield and product purity with low cost.
Description
Technical field
The present invention relates to the field of chemical synthesis, relate to the synthetic method of oxazole pyridine compounds especially.
Background technology
The oxazole pyridine compounds is the important medicine of a class, pesticide intermediate.At present, the preparation method of Guan Yu oxazole pyridone mainly contains following several in the document:
(1) adopt phosgene to Cheng the oxazole pyridone with adjacent hydroxy amino pyridine He, this method has adopted phosgene as carbonylation agent, and phosgene is hypertoxic gas, operational difficulty, and phosgene can only fix a point to produce and use, so this method is difficult to use to general business enterprise expand;
(2) adopt CO to Cheng the oxazole pyridone with adjacent hydroxy amino pyridine He, this method is owing to adopt CO under high pressure synthetic, so very high to the requirement of equipment;
(3) adopt carbonyl dimidazoles to Cheng the oxazole pyridone with adjacent hydroxy amino pyridine He, this synthetic method cost is too high;
(4) adopt first He Cheng oxazole pyrithione, reoxidize two step synthesis methods of He Cheng oxazole pyridone, this method production cycle is long, and has a large amount of solid waste to produce.
Summary of the invention
The objective of the invention is to disclose a kind of new employing carbonylation agent---two trichloromethyl carbonates and adjacent hydroxy amino pyridine compounds and their react in solvent under action of evocating, the method for Zhi Bei oxazole pyridone.
Its concrete technical scheme is as follows: with adjacent hydroxy amino pyridine, two trichloromethyl carbonate (being commonly called as solid phosgene, triphosgene) is raw material, with halohydrocarbon etc. is solvent, with pyridine etc. is initiator, oxyhydroxide or its carbonate with pyridine, dimethyl formamide, triethylamine, basic metal or alkaline-earth metal are acid binding agent, at a certain temperature, obtain target product through stirring reaction for some time.
Raw material is adjacent hydroxy amino pyridine and two trichloromethyl carbonate, and the mol ratio of two trichloromethyl carbonates and adjacent hydroxy amino pyridine is 0.3～0.7, and preferred value is 0.4～0.5; Adjacent hydroxy amino pyridine is 2-amino-3-pyridone and halogenated compound such as 2-amino-3-hydroxyl-5-chloropyridine, 2-amino-3-hydroxyl-5-bromopyridine etc.;
Solvent is a halohydrocarbon etc., and it comprises methylene dichloride, ethylene dichloride, trichloromethane, tetrachloromethane, chlorobenzene, benzene,toluene,xylene, tetrahydrofuran (THF); Solvent is 1～10 with the weight ratio of two trichloromethyl carbonates, and preferred value is 2～5;
Initiator is a pyridine etc., and it comprises pyridine, dimethyl formamide, triethylamine; Initiator is 0.001～1 with the mol ratio of two trichloromethyl carbonates, and preferred value is 0.01～0.2;
Acid binding agent is oxyhydroxide or its carbonate or its supercarbonate of pyridine, dimethyl formamide, triethylamine, basic metal or alkaline-earth metal; Acid binding agent is 6～12 with the mol ratio of two trichloromethyl carbonates, and preferred value is 7～9.
During concrete operations, two trichloromethyl carbonates are dissolved in the solvent wiring solution-forming earlier; In reactor, add adjacent hydroxy amino pyridine, initiator and acid binding agent then respectively, under stirring condition, in reaction mass, drip the two trichloromethyl carbonate solution prepare, stirring reaction 0.5～5 hour under 0～100 ℃ temperature and obtain target product.
The present invention compared with prior art, its major advantage is: the two trichloromethyl carbonates of (1) raw material are solid, extremely stable at normal temperatures, its temperature of initial decomposition is 130 ℃, this product is when unrestrained, can clean collection does not influence use, and nubbin can not have influence to health and environment with the flushing of 5～10% ammoniacal liquor.Therefore all very safe in transportation, storage and use; (2) temperature of reaction is low, and equipment is not had particular requirement, and common corrosion resistant apparatus is promptly applicable; (3) reaction times weak point, reaction is easy to control, and aftertreatment is simple, yield height, product purity height; (4) production cost is low, is easy to apply.
Embodiment
Embodiment 1:
Earlier the two trichloromethyl carbonates of 0.4mol are dissolved in the ethylene dichloride of 300g.Add 1mol 2-amino-3-pyridone in reaction flask, the 3.5mol pyridine is under 40 ℃ of temperature, drip the dichloroethane solution of above-mentioned two trichloromethyl carbonates at leisure, in the dropping process, have lurid solid matter to separate out gradually, after dropwising, insulation reaction 1 hour reclaims solvent, residue adds an amount of water, promptly has solid matter to separate out, and filters, filter cake washes twice with water, oven dry ， De oxazole pyridone 128.9g, yield 94.8%, fusing point 211-212 ℃.
Embodiment 2:
Earlier the two trichloromethyl carbonates of 0.4mol are dissolved in the trichloromethane of 350g.Add 1mol 2-amino-3-hydroxyl-5-chloropyridine in reaction flask, the 3.5mol pyridine drips the chloroform soln of above-mentioned two trichloromethyl carbonates at leisure under 40 ℃ of temperature, after dropwising, insulation reaction 2 hours reclaims solvent, residue adds an amount of water, promptly have solid matter to separate out, filter, filter cake washes with water twice, oven dry, get 6-Lv oxazole pyridone 153.3g, yield 90.2%, fusing point 187-188 ℃.
Embodiment 3:
Earlier the two trichloromethyl carbonates of 0.4mol are dissolved in the ethylene dichloride of 300g.In reaction flask, add 1mol 2-amino-3-pyridone, 6g pyridine, 3mol triethylamine, under 60 ℃ of temperature, drip the dichloroethane solution of above-mentioned two trichloromethyl carbonates at leisure, after dropwising, insulation reaction 1 hour, reclaim solvent, residue adds an amount of water, promptly has solid matter to separate out, filter, filter cake washes twice with water, oven dry ， De oxazole pyridone 125.1g, yield 92.0%, fusing point 211-212 ℃.
Claims (7)
1. the synthetic method of Yi Zhong oxazole pyridine compounds is characterized in that, is raw material with two trichloromethyl carbonates and adjacent hydroxy amino pyridine, and its mol ratio is 0.3～0.7; In the presence of solvent, initiator and acid binding agent, solvent is 1～10 with the weight ratio of two trichloromethyl carbonates, the mol ratio of initiator, acid binding agent and two trichloromethyl carbonates is respectively 0.001～1 and 6～12, under 0～100 ℃ temperature, through stirring reaction 0.5～5 hour and De Dao the oxazole pyridine compounds.
2. as the synthetic method of claim 1 De oxazole pyridine compounds, it is characterized in that the mol ratio of described pair of trichloromethyl carbonate and adjacent hydroxy amino pyridine is 0.4～0.5.
3. as the synthetic method of claim 1 or 2 De oxazole pyridine compounds, it is characterized in that, described adjacent hydroxy amino pyridine is 2-amino-3-pyridone and halogenated compound thereof, as 2-amino-3-hydroxyl-5-chloropyridine or 2-amino-3-hydroxyl-5-bromopyridine.
4. as the synthetic method of claim 1 De oxazole pyridine compounds, it is characterized in that, described solvent comprises methylene dichloride or ethylene dichloride or trichloromethane or tetrachloromethane or chlorobenzene or benzene or toluene or dimethylbenzene or tetrahydrofuran (THF), and solvent is 2～5 with the weight ratio of two trichloromethyl carbonates.
5. as the synthetic method of claim 1 De oxazole pyridine compounds, it is characterized in that described initiator is pyridine or dimethyl formamide or triethylamine, initiator is 0.01～0.2 with the mol ratio of two trichloromethyl carbonates.
6. as the synthetic method of claim 1 De oxazole pyridine compounds, it is characterized in that, described acid binding agent is oxyhydroxide or its carbonate or its supercarbonate of pyridine or dimethyl formamide or triethylamine or basic metal and alkaline-earth metal, and acid binding agent is 7～9 with the mol ratio of two trichloromethyl carbonates.
7. as the synthetic method of the oxazole pyridine compounds of claim 5 or 6, it is characterized in that described initiator can be with a kind of reagent or different reagent with acid binding agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100069099A CN100522971C (en) | 2005-01-12 | 2005-01-12 | Method for synthesizing oxazole pyridone compound |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100069099A CN100522971C (en) | 2005-01-12 | 2005-01-12 | Method for synthesizing oxazole pyridone compound |
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| CN1803802A true CN1803802A (en) | 2006-07-19 |
| CN100522971C CN100522971C (en) | 2009-08-05 |
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| CNB2005100069099A Expired - Fee Related CN100522971C (en) | 2005-01-12 | 2005-01-12 | Method for synthesizing oxazole pyridone compound |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103242345A (en) * | 2012-09-14 | 2013-08-14 | 日出实业集团有限公司 | Synthetic method of picoline phosphate intermediate 6-chloxazole [4,5-b] pyridine-2(3H) acetone |
| CN105924454A (en) * | 2016-05-08 | 2016-09-07 | 邯郸市赵都精细化工有限公司 | Preparation method of azamethiphos intermediate 3H-oxazolo[4,5-b]pyridin-2-one |
| CN108047247A (en) * | 2017-12-22 | 2018-05-18 | 中山市小榄企业服务有限公司 | The synthetic method of Yi Zhong oxazole pyridine compounds |
| CN114560873A (en) * | 2021-12-27 | 2022-05-31 | 浙江日出药业有限公司 | Preparation method of 3-chloromethyl-6-chloro-oxazole [4,5-b ] pyridine-2 (3H) ketone |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1212323C (en) * | 2001-07-01 | 2005-07-27 | 中国科学院福建物质结构研究所 | Process for synthesizing oxazole [4,5-6] pyridine-2 (3H) one |
-
2005
- 2005-01-12 CN CNB2005100069099A patent/CN100522971C/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103242345A (en) * | 2012-09-14 | 2013-08-14 | 日出实业集团有限公司 | Synthetic method of picoline phosphate intermediate 6-chloxazole [4,5-b] pyridine-2(3H) acetone |
| CN103242345B (en) * | 2012-09-14 | 2015-03-11 | 日出实业集团有限公司 | Synthetic method of picoline phosphate intermediate 6-chloxazole [4,5-b] pyridine-2(3H) acetone |
| CN105924454A (en) * | 2016-05-08 | 2016-09-07 | 邯郸市赵都精细化工有限公司 | Preparation method of azamethiphos intermediate 3H-oxazolo[4,5-b]pyridin-2-one |
| CN108047247A (en) * | 2017-12-22 | 2018-05-18 | 中山市小榄企业服务有限公司 | The synthetic method of Yi Zhong oxazole pyridine compounds |
| CN114560873A (en) * | 2021-12-27 | 2022-05-31 | 浙江日出药业有限公司 | Preparation method of 3-chloromethyl-6-chloro-oxazole [4,5-b ] pyridine-2 (3H) ketone |
| CN114560873B (en) * | 2021-12-27 | 2023-02-28 | 浙江日出药业有限公司 | Preparation method of 3-chloromethyl-6-chloro-oxazole [4,5-b ] pyridine-2 (3H) ketone |
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| CN100522971C (en) | 2009-08-05 |
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Granted publication date: 20090805 Termination date: 20120112 |