CN104945312A - Preparation method of 2,6-dichlorine methyl pyridine hydrochloride - Google Patents
Preparation method of 2,6-dichlorine methyl pyridine hydrochloride Download PDFInfo
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- CN104945312A CN104945312A CN201510352643.7A CN201510352643A CN104945312A CN 104945312 A CN104945312 A CN 104945312A CN 201510352643 A CN201510352643 A CN 201510352643A CN 104945312 A CN104945312 A CN 104945312A
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/26—Radicals substituted by halogen atoms or nitro radicals
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Abstract
The invention belongs to the field of organic synthesis and particularly relates to a preparation method of 2,6-dichlorine methyl pyridine hydrochloride. The method includes the following steps that 1, 2,6-di-chlorine methyl pyridine serves as a raw material to prepare 2,6-pyridinedicarboxylic acid; 2, the 2,6-pyridinedicarboxylic acid and methanol generate 2,6-pyridinedicarboxylic acid dimethyl under an acidic condition; 3, the 2,6-pyridinedicarboxylic acid dimethyl is reduced to 2,6-pyridine dimethyl carbinol; 4, the 2,6-pyridine dimethyl carbinol reacts with thionyl chloride to obtain the objective product of the 2,6-dichlorine methyl pyridine hydrochloride. The preparation method of the 2,6-dichlorine methyl pyridine hydrochloride has the advantages that a common chemical material containing a pyridine ring is adopted to conduct an acetyl reaction, the reaction steps are less, the cost is low, the toxicity is small, the reaction yield rate is high, and the preparation method of the 2,6-dichlorine methyl pyridine hydrochloride is suitable for industrial production.
Description
Technical field
The invention belongs to organic synthesis field, be specifically related to a kind of preparation method of 2,6-dichloromethyl pyridine hydrochloride.
Background technology
Pyridine and its derivatives is distributed in nature widely.Many plant constituents are as all contained pyridine ring compound in the structure of alkaloid etc., they are the bases producing many important compound, are indispensable raw materials during medicine, agricultural chemicals, dyestuff, tensio-active agent, rubber ingredients, fodder additives, foodstuff additive, tackiness agent etc. are produced.
2,6-dichloromethyl pyridine hydrochloride is a kind of important medicine and pesticide intermediate, and the method usually adopted at present is by picolyl, then reacts with the precious metal industrial chemicals that lithium methide, methyl iodide etc. are expensive; Or directly cyclization becomes on 2,6-position to have methyl, more logical chlorine, carry out chlorination reaction.But be raw material with lithium methide, methyl iodide etc., cost is high, precious metal be reclaimed and iodine element is cumbersome; Large by methyl-sulfate toxicity, more dangerous for dosing operation.
Summary of the invention
The object of the invention is to overcome the technical deficiency that in prior art, cost is high, material toxicity is large, provide that a kind of cost is low, route is short, be suitable for the preparation method of 2,6-dichloromethyl pyridine hydrochlorides of suitability for industrialized production.
In order to solve the problems of the technologies described above, the technical solution used in the present invention is as follows:
A kind of preparation method of 2,6-dichloromethyl pyridine hydrochloride, the method comprises the following steps:
(1) with 2,6-lutidine for raw material, with water as solvent, 2 are oxidized to potassium permanganate, 6-dinicotinic acid, wherein, 2, the mol ratio of 6-lutidine and potassium permanganate is 1:4-5, oxidizing temperature is maintained 75-80 DEG C, and heating 35min, has reacted and reaction solution is adjusted to acidity, be cooled to 20-25 DEG C again and obtain 2,6-dinicotinic acid;
(2) 2,6-dinicotinic acids and methyl alcohol generate 2,6-dinicotinic acid dimethyl ester in acid condition, and wherein the mol ratio of 2,6-dinicotinic acids and methyl alcohol is 1:2.5-3;
(3) 2,6-dinicotinic acid dimethyl esters are reduced to 2,6-pyridine dimethanol;
(4) 2,6-pyridine dimethanols and sulfur oxychloride are obtained by reacting object product 2,6-dichloromethyl pyridine hydrochloride, and the mol ratio of 2,6-pyridine dimethanol and sulfur oxychloride is 1:2.2-2.5.
Further, in described step (1), potassium permanganate adds under the condition of 80 DEG C in batches.
Further, in described step (1), PH regulates is, with the hydrochloric acid of 2mol/l, the pH value of reaction solution is adjusted to 3-4.
Further, in described step (1), the temperature of cold filtration is 25 DEG C.
Further, the reductive agent adopted in described step (3) is sodium borohydride, and the mol ratio of described 2,6-dinicotinic acid dimethyl esters and sodium borohydride is 1:6-8, adds Lewis acid in described reduction reaction.
Further, described Lewis acid is aluminum chloride.
Further, the solvent that described reduction reaction adopts is THF and toluene is that 1:1 mixes with volume ratio.
Reaction equation of the present invention is:
Employing the invention has the beneficial effects as follows: the present invention adopts the conventional industrial chemicals containing pyridine ring to carry out acetylating reaction, and reactions steps is few, and cost is low, and toxicity is little, and yield is high, is suitable for suitability for industrialized production.
Embodiment
Below in conjunction with specific embodiment, the present invention will be further described.These embodiments are illustrative completely, and they are only used for being specifically described the present invention, should not be construed as limitation of the present invention.
Embodiment 1
(1) in the flask of 250ml, 2 are added, 6-lutidine (21.4g, 0.2mol), water 150ml, be heated to 80 DEG C, add potassium permanganate (126.4g, 0.8mol), holding temperature is at 75-80 DEG C of heated and stirred 35min in batches, thin-layer chromatography trace analysis, the pH value of reaction solution is adjusted to 3 with the hydrochloric acid of 2mol/l by question response completely, reacting liquid temperature is cooled to 20 DEG C and obtains 2,6-dinicotinic acid.
(2) 2,6-dinicotinic acids and methyl alcohol (16g, 0.5mol) generate 2,6-dinicotinic acid dimethyl ester under vitriol oil effect.
(3) 2,6-dinicotinic acid dimethyl esters are dissolved in the solvent that 75mlTHF and 75ml toluene mixes, and 0-5 DEG C adds sodium borohydride (45.4g in batches, 1.2mol) and aluminum chloride, add and continue reaction 3-4h, thin-layer chromatography trace analysis is to 2, the 6-pyridine dimethanols that react completely to obtain.
React with sulfur oxychloride (52.4g, 0.44mol) in methanol solution after (4) 2,6-pyridine dimethanols, thin-layer chromatography trace analysis, question response is all converted into stopped reaction after 2,6-dichloromethyl pyridine hydrochloride, suction filtration, obtains product 39.8g, and productive rate is 80%(molar yield).
Embodiment 2
(1) in the flask of 250ml, 2 are added, 6-lutidine (21.4g, 0.2mol), water 150ml, be heated to 80 DEG C, add potassium permanganate (142.2g, 0.9mol), holding temperature is at 75-80 DEG C of heated and stirred 35min in batches, thin-layer chromatography trace analysis, the pH value of reaction solution is adjusted to 4 with the hydrochloric acid of 2mol/l by question response completely, reacting liquid temperature is cooled to 25 DEG C and obtains 2,6-dinicotinic acid.
(2) 2,6-dinicotinic acids and methyl alcohol (17.9g, 0.56mol) generate 2,6-dinicotinic acid dimethyl ester under vitriol oil effect.
(3) 2,6-dinicotinic acid dimethyl esters are dissolved in the solvent that 75mlTHF and 75ml toluene mixes, and 0-5 DEG C adds sodium borohydride (53g in batches, 1.4mol) and aluminum chloride, add and continue reaction 3-4h, thin-layer chromatography trace analysis is to 2, the 6-pyridine dimethanols that react completely to obtain.
React with sulfur oxychloride (54.7g, 0.46mol) in methanol solution after (4) 2,6-pyridine dimethanols, thin-layer chromatography trace analysis, question response is all converted into stopped reaction after 2,6-dichloromethyl pyridine hydrochloride, suction filtration, obtains product 40.9g, and productive rate is 82%(molar yield).
Embodiment 3
(1) in the flask of 250ml, 2 are added, 6-lutidine (21.4g, 0.2mol), water 150ml, be heated to 80 DEG C, add potassium permanganate (15.8g, 1.0mol), holding temperature is at 75-80 DEG C of heated and stirred 35min in batches, thin-layer chromatography trace analysis, the pH value of reaction solution is adjusted to 3 with the hydrochloric acid of 2mol/l by question response completely, reacting liquid temperature is cooled to 25 DEG C and obtains 2,6-dinicotinic acid.
(2) 2,6-dinicotinic acids and methyl alcohol (19.2g, 0.6 mol) generate 2,6-dinicotinic acid dimethyl ester under vitriol oil effect.
(3) 2,6-dinicotinic acid dimethyl esters are dissolved in the solvent that 75mlTHF and 75ml toluene mixes, and 0-5 DEG C adds sodium borohydride (68.1g in batches, 1.8mol) and aluminum chloride, add and continue reaction 3-4h, thin-layer chromatography trace analysis is to 2, the 6-pyridine dimethanols that react completely to obtain.
React with sulfur oxychloride (59.5g, 0.5 mol) in methanol solution after (4) 2,6-pyridine dimethanols, thin-layer chromatography trace analysis, question response is all converted into stopped reaction after 2,6-dichloromethyl pyridine hydrochloride, suction filtration, obtains product 38.8g, and productive rate is 78%(molar yield).
Claims (7)
1. the preparation method of a dichloromethyl pyridine hydrochloride, is characterized in that the method comprises the following steps:
(1) with 2,6-lutidine for raw material, with water as solvent, 2 are oxidized to potassium permanganate, 6-dinicotinic acid, wherein, 2, the mol ratio of 6-lutidine and potassium permanganate is 1:4-5, oxidizing temperature is maintained 75-80 DEG C, and heating 35min, has reacted and reaction solution is adjusted to acidity, be cooled to 20-25 DEG C again and obtain 2,6-dinicotinic acid;
(2) 2,6-dinicotinic acids and methyl alcohol generate 2,6-dinicotinic acid dimethyl ester in acid condition, and wherein the mol ratio of 2,6-dinicotinic acids and methyl alcohol is 1:2.5-3;
(3) 2,6-dinicotinic acid dimethyl esters are reduced to 2,6-pyridine dimethanol;
(4) 2,6-pyridine dimethanols and sulfur oxychloride are obtained by reacting object product 2,6-dichloromethyl pyridine hydrochloride, and the mol ratio of 2,6-pyridine dimethanol and sulfur oxychloride is 1:2.2-2.5.
2. the preparation method of a kind of 2,6-dichloromethyl pyridine hydrochlorides according to claim 1, is characterized in that: in described step (1), potassium permanganate adds under the condition of 80 DEG C in batches.
3. the preparation method of a kind of 2,6-dichloromethyl pyridine hydrochlorides according to claim 1, is characterized in that: in described step (1), PH regulates is, with the hydrochloric acid of 2mol/l, the pH value of reaction solution is adjusted to 3-4.
4. the preparation method of a kind of 2,6-dichloromethyl pyridine hydrochlorides according to claim 1, is characterized in that: in described step (1), the temperature of cold filtration is 25 DEG C.
5. according to claim 1 a kind of 2, the preparation method of 6-dichloromethyl pyridine hydrochloride, it is characterized in that: the reductive agent adopted in described step (3) is sodium borohydride, described 2, the mol ratio of 6-dinicotinic acid dimethyl ester and sodium borohydride is 1:6-8, adds Lewis acid in described reduction reaction.
6. the preparation method of a kind of 2,6-dichloromethyl pyridine hydrochlorides according to claim 5, is characterized in that: described Lewis acid is aluminum chloride.
7. the preparation method of a kind of 2,6-dichloromethyl pyridine hydrochlorides according to claim 5, is characterized in that: the solvent that described reduction reaction adopts is THF and toluene is that 1:1 mixes with volume ratio.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105884682A (en) * | 2016-05-24 | 2016-08-24 | 合肥工业大学 | Synthetic method for 2,6-pyridine dimethyl formate crystal |
| CN112047878A (en) * | 2020-10-15 | 2020-12-08 | 郑州猫眼农业科技有限公司 | Preparation method of 4-bromo-6-chloropyridine-2-carboxylic acid |
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| WO1997031005A1 (en) * | 1996-02-23 | 1997-08-28 | The Dow Chemical Company | Polyazamacrocyclofluoromonoalkylphosphonic acids, and their complexes, for use as contrast agents |
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| CN102659961A (en) * | 2012-05-09 | 2012-09-12 | 浙江大学 | Cobalt catalyst and application thereof in 1,3-butadiene polymerization reaction |
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2015
- 2015-06-24 CN CN201510352643.7A patent/CN104945312A/en active Pending
Patent Citations (4)
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| US5480990A (en) * | 1991-12-10 | 1996-01-02 | The Dow Chemical Company | Bicyclopolyazamacrocyclocarboxylic acid complexes for use as contrast agents |
| WO1997031005A1 (en) * | 1996-02-23 | 1997-08-28 | The Dow Chemical Company | Polyazamacrocyclofluoromonoalkylphosphonic acids, and their complexes, for use as contrast agents |
| CN1312811A (en) * | 1998-06-15 | 2001-09-12 | 荷兰联合利华有限公司 | Bleach catalysts and formulations containing them |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105884682A (en) * | 2016-05-24 | 2016-08-24 | 合肥工业大学 | Synthetic method for 2,6-pyridine dimethyl formate crystal |
| CN112047878A (en) * | 2020-10-15 | 2020-12-08 | 郑州猫眼农业科技有限公司 | Preparation method of 4-bromo-6-chloropyridine-2-carboxylic acid |
| CN112047878B (en) * | 2020-10-15 | 2022-04-19 | 郑州猫眼农业科技有限公司 | Preparation method of 4-bromo-6-chloropyridine-2-carboxylic acid |
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Application publication date: 20150930 |