CN109748844A - A kind of preparation method of 2,6- dichloromethyl pyridine hydrochloride - Google Patents
A kind of preparation method of 2,6- dichloromethyl pyridine hydrochloride Download PDFInfo
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- CN109748844A CN109748844A CN201711082552.1A CN201711082552A CN109748844A CN 109748844 A CN109748844 A CN 109748844A CN 201711082552 A CN201711082552 A CN 201711082552A CN 109748844 A CN109748844 A CN 109748844A
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- pyridine hydrochloride
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- pyridinedicarboxylic acid
- dichloromethyl
- pyridine
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Abstract
The invention belongs to organic synthesis fields, and in particular to the preparation method of one kind 2,6- dichloromethyl pyridine hydrochloride, method includes the following steps: (1) with 2,6- lutidines be raw material, prepare 2,6- pyridinedicarboxylic acid；(2) 2,6- pyridinedicarboxylic acid and methanol generate 2,6- pyridinedicarboxylic acid dimethyl ester in acid condition；(3) 2,6- pyridinedicarboxylic acid dimethyl ester is reduced to 2,6- pyridine dimethanol；(4) 2,6- pyridine dimethanol reacts to obtain purpose product 2,6- dichloromethyl pyridine hydrochloride with thionyl chloride.Using the beneficial effects of the present invention are: the present invention carries out acetylating reaction using the industrial chemicals commonly containing pyridine ring, reaction step is few, at low cost, small toxicity, high income, is suitable for industrialized production.
Description
Technical field
The invention belongs to organic synthesis fields, and in particular to the preparation method of one kind 2,6- dichloromethyl pyridine hydrochloride.
Background technique
Pyridine and its derivatives are widely distributed in nature.All contain in the structure of many plant components such as alkaloid
Pyridine cycle compound, they are the bases for producing many important compounds, are medicine, pesticide, dyestuff, surfactant, rubber
Indispensable raw material in the production such as auxiliary agent, feed addictive, food additives, adhesive.
2,6- dichloromethyl pyridine hydrochlorides are a kind of important medicine and pesticide intermediate, the method generallyd use at present
It is to be reacted by picolyl, then with the noble metal industrial chemicals of the valuableness such as lithium methide, iodomethane；Either direct cyclization
At having methyl, then logical chlorine on the position 2,6-, chlorination reaction is carried out.But be raw material with lithium methide, iodomethane etc., it is at high cost,
It recycles noble metal and iodine is more troublesome；It is big with dimethyl suflfate toxicity, for dosing operation than relatively hazardous.
Summary of the invention
The purpose of the present invention is overcoming at high cost, technical deficiency that material toxicity is big in the prior art, a kind of cost is provided
It is low, route is short, the preparation method of 2, the 6- dichloromethyl pyridine hydrochloride suitable for industrialized production.
In order to solve the above-mentioned technical problem, The technical solution adopted by the invention is as follows:
The preparation method of one kind 2,6- dichloromethyl pyridine hydrochloride, method includes the following steps:
It (1) is that raw material is oxidized with water as solvent with potassium permanganate as 2,6- pyridine diformazan with 2,6- lutidines
Acid, wherein the molar ratio of 2,6- lutidines and potassium permanganate is 1:4-5, and oxidizing temperature is maintained 75-80 DEG C, heating
35min has reacted reaction solution being adjusted to acidity, is cooled to 20-25 DEG C and obtains 2,6- pyridinedicarboxylic acid；
(2) 2,6- pyridinedicarboxylic acid and methanol generate 2,6- pyridinedicarboxylic acid dimethyl ester in acid condition, wherein 2,6-
The molar ratio of pyridinedicarboxylic acid and methanol is 1:2.5-3；
(3) 2,6- pyridinedicarboxylic acid dimethyl ester is reduced to 2,6- pyridine dimethanol；
(4) 2,6- pyridine dimethanol react to obtain with thionyl chloride purpose product 2,6- dichloromethyl pyridine hydrochloride, and 2,
The molar ratio of 6- pyridine dimethanol and thionyl chloride is 1:2.2-2.5.
Further, potassium permanganate is added portionwise under conditions of 80 DEG C in the step (1).
Further, it by the pH value adjustment of reaction solution is 3-4 that PH adjusting, which is with the hydrochloric acid of 2mol/l, in the step (1).
Further, the temperature of cold filtration is 25 DEG C in the step (1).
Further, the reducing agent used in the step (3) is sodium borohydride, 2, the 6- pyridinedicarboxylic acid dimethyl ester
Molar ratio with sodium borohydride is 1:6-8, and Lewis acid is added in the reduction reaction.
Further, the Lewis acid is alchlor.
Further, the solvent that the reduction reaction uses is that THF and toluene are mixed with volume ratio for 1:1.
Reaction equation of the invention are as follows:
Using the beneficial effects of the present invention are: the present invention carries out acetyl group using the industrial chemicals commonly containing pyridine ring
Change reaction, reaction step is few, at low cost, small toxicity, high income, is suitable for industrialized production.
Specific embodiment
The present invention will be further described combined with specific embodiments below.These embodiments be entirely it is illustrative, they
Only it is used to that the present invention is specifically described, should not be construed as limiting the invention.
Embodiment 1
(1) 2,6- lutidines (21.4g, 0.2mol) is added in the flask of 250ml, water 150ml is heated to 80
DEG C, be added portionwise potassium permanganate (126.4g, 0.8mol), maintain temperature in 75-80 DEG C of heating stirring 35min, thin-layer chromatography with
The pH value adjustment of reaction solution with the hydrochloric acid of 2mol/l is 3 to fully reacting by track analysis, and reacting liquid temperature is cooled to 20 DEG C
2,6- pyridinedicarboxylic acid.
(2) 2,6- pyridinedicarboxylic acid and methanol (16g, 0.5mol) generate 2,6- pyridinedicarboxylic acid two under concentrated sulfuric acid effect
Methyl esters.
(3) 2,6- pyridinedicarboxylic acid dimethyl ester are dissolved in the solvent that 75mlTHF and 75ml toluene mixes, and 0-5 DEG C
Sodium borohydride (45.4g, 1.2mol) and alchlor is added portionwise, the 3-4h that adds that the reaction was continued, thin-layer chromatography trace analysis is extremely
Fully reacting obtains 2,6- pyridine dimethanol.
It is reacted in methanol solution with thionyl chloride (52.4g, 0.44mol) after (4) 2,6- pyridine dimethanol, thin-layer chromatography
Trace analysis, wait react be completely converted into 2,6- dichloromethyl pyridine hydrochloride after stop reaction, filter, obtain product 39.8g, produce
Rate is 80% (molar yield).
Embodiment 2
(1) 2,6- lutidines (21.4g, 0.2mol) is added in the flask of 250ml, water 150ml is heated to 80
DEG C, be added portionwise potassium permanganate (142.2g, 0.9mol), maintain temperature in 75-80 DEG C of heating stirring 35min, thin-layer chromatography with
The pH value adjustment of reaction solution with the hydrochloric acid of 2mol/l is 4 to fully reacting by track analysis, and reacting liquid temperature is cooled to 25 DEG C
2,6- pyridinedicarboxylic acid.
(2) 2,6- pyridinedicarboxylic acid and methanol (17.9g, 0.56mol) generate 2,6- pyridine diformazan under concentrated sulfuric acid effect
Dimethyl phthalate.
(3) 2,6- pyridinedicarboxylic acid dimethyl ester are dissolved in the solvent that 75mlTHF and 75ml toluene mixes, and 0-5 DEG C
Sodium borohydride (53g, 1.4mol) and alchlor is added portionwise, the 3-4h that adds that the reaction was continued, thin-layer chromatography trace analysis is to anti-
2,6- pyridine dimethanol should be obtained completely.
It is reacted in methanol solution with thionyl chloride (54.7g, 0.46mol) after (4) 2,6- pyridine dimethanol, thin-layer chromatography
Trace analysis, wait react be completely converted into 2,6- dichloromethyl pyridine hydrochloride after stop reaction, filter, obtain product 40.9g, produce
Rate is 82% (molar yield).
Embodiment 3
(1) 2,6- lutidines (21.4g, 0.2mol) is added in the flask of 250ml, water 150ml is heated to 80
DEG C, it is added portionwise potassium permanganate (15.8g, 1.0mol), maintains temperature in 75-80 DEG C of heating stirring 35min, thin-layer chromatography tracking
The pH value adjustment of reaction solution with the hydrochloric acid of 2mol/l is 3 to fully reacting by analysis, by reacting liquid temperature be cooled to 25 DEG C 2,
6- pyridinedicarboxylic acid.
(2) 2,6- pyridinedicarboxylic acid and methanol (19.2g, 0.6mol) generate 2,6- pyridinedicarboxylic acid under concentrated sulfuric acid effect
Dimethyl ester.
(3) 2,6- pyridinedicarboxylic acid dimethyl ester are dissolved in the solvent that 75mlTHF and 75ml toluene mixes, and 0-5 DEG C
Sodium borohydride (68.1g, 1.8mol) and alchlor is added portionwise, the 3-4h that adds that the reaction was continued, thin-layer chromatography trace analysis is extremely
Fully reacting obtains 2,6- pyridine dimethanol.
It is reacted in methanol solution with thionyl chloride (59.5g, 0.5mol) after (4) 2,6- pyridine dimethanol, thin-layer chromatography
Trace analysis, wait react be completely converted into 2,6- dichloromethyl pyridine hydrochloride after stop reaction, filter, obtain product 38.8g, produce
Rate is 78% (molar yield).
Claims (7)
1. one kind 2, the preparation method of 6- dichloromethyl pyridine hydrochloride, it is characterised in that method includes the following steps:
(1) it with 2,6- lutidines for raw material, with water as solvent, is oxidized with potassium permanganate as 2,6- pyridinedicarboxylic acid,
Wherein, the molar ratio of 2,6- lutidines and potassium permanganate is 1:4-5, and oxidizing temperature is maintained 75-80 DEG C, heats 35min,
It has reacted and reaction solution is adjusted to acidity, be cooled to 20-25 DEG C and obtain 2,6- pyridinedicarboxylic acid；
(2) 2,6- pyridinedicarboxylic acid and methanol generate 2,6- pyridinedicarboxylic acid dimethyl ester in acid condition, wherein 2,6- pyridines
The molar ratio of dioctyl phthalate and methanol is 1:2.5-3；
(3) 2,6- pyridinedicarboxylic acid dimethyl ester is reduced to 2,6- pyridine dimethanol；
(4) 2,6- pyridine dimethanol react to obtain purpose product 2,6- dichloromethyl pyridine hydrochloride, 2,6- pyrroles with thionyl chloride
The molar ratio of pyridine dimethanol and thionyl chloride is 1:2.2-2.5.
2. a kind of preparation method of 2,6- dichloromethyl pyridine hydrochloride according to claim 1, it is characterised in that: described
Potassium permanganate is added portionwise under conditions of 80 DEG C in step (1).
3. a kind of preparation method of 2,6- dichloromethyl pyridine hydrochloride according to claim 1, it is characterised in that: described
It by the pH value adjustment of reaction solution is 3-4 that PH adjusting, which is with the hydrochloric acid of 2mol/l, in step (1).
4. a kind of preparation method of 2,6- dichloromethyl pyridine hydrochloride according to claim 1, it is characterised in that: described
The temperature of cold filtration is 25 DEG C in step (1).
5. a kind of preparation method of 2,6- dichloromethyl pyridine hydrochloride according to claim 1, it is characterised in that: described
The reducing agent used in step (3) is sodium borohydride, and the molar ratio of 2, the 6- pyridinedicarboxylic acid dimethyl ester and sodium borohydride is
Lewis acid is added in the reduction reaction by 1:6-8.
6. a kind of preparation method of 2,6- dichloromethyl pyridine hydrochloride according to claim 5, it is characterised in that: described
Lewis acid is alchlor.
7. a kind of preparation method of 2,6- dichloromethyl pyridine hydrochloride according to claim 5, it is characterised in that: described
The solvent that reduction reaction uses is that THF and toluene are mixed with volume ratio for 1:1.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711082552.1A CN109748844A (en) | 2017-11-07 | 2017-11-07 | A kind of preparation method of 2,6- dichloromethyl pyridine hydrochloride |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201711082552.1A CN109748844A (en) | 2017-11-07 | 2017-11-07 | A kind of preparation method of 2,6- dichloromethyl pyridine hydrochloride |
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| CN201711082552.1A Withdrawn CN109748844A (en) | 2017-11-07 | 2017-11-07 | A kind of preparation method of 2,6- dichloromethyl pyridine hydrochloride |
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2017
- 2017-11-07 CN CN201711082552.1A patent/CN109748844A/en not_active Withdrawn
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