CN109761888A - A kind of synthetic method of 4- chloromethyl pyridine hydrochloride - Google Patents
A kind of synthetic method of 4- chloromethyl pyridine hydrochloride Download PDFInfo
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- CN109761888A CN109761888A CN201711095832.6A CN201711095832A CN109761888A CN 109761888 A CN109761888 A CN 109761888A CN 201711095832 A CN201711095832 A CN 201711095832A CN 109761888 A CN109761888 A CN 109761888A
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- isonicotinic acid
- pyridine hydrochloride
- chloromethyl pyridine
- synthetic method
- pyridinemethanol
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Abstract
The invention belongs to organic synthesis fields, more particularly to a kind of synthetic method of 4- chloromethyl pyridine hydrochloride, method includes the following steps: (1) using 4- picoline as raw material, with water as solvent, is oxidized with potassium permanganate as Isonicotinic acid, wherein, the molar ratio of 4- picoline and potassium permanganate is 1:2.1-2.3, and oxidizing temperature is 75-80 DEG C, heats 35min, reaction solution is adjusted to acidity by fully reacting, then cold filtration obtains Isonicotinic acid；(2) Isonicotinic acid and methanol generate Isonicotinic acid methyl esters in acid condition, and wherein the molar ratio of Isonicotinic acid and methanol is 1:1.3；(3) reduction Isonicotinic acid methyl esters is 4- pyridinemethanol；(4) 4- pyridinemethanol reacts to obtain with thionyl chloride purpose product 4- chloromethyl pyridine hydrochloride, and the molar ratio of 4- pyridinemethanol and thionyl chloride is 1:1.1-1.3.
Description
Technical field
The invention belongs to organic synthesis fields, and in particular to a kind of synthetic method of 4- chloromethyl pyridine hydrochloride.
Background technique
Chloromethyl pyridine hydrochloride is the important chemical industry of various pesticides, medicine intermediate, Insecticides (tech) & Herbicides (tech), fungicide
Raw material.Current production method carries out chlorine using the directly upper methyl of pyridine, with the noble metals industrial chemicals such as lithium methide, then logical chlorine
Generation reaction.It is easier to connect industrial chemicals intermediate and bulk pharmaceutical chemicals that other groups synthesis has high added value after pyridine chloromethylation.
But be raw material with lithium methide etc., cost price pressure is big, and Yao Huishou noble metal is more troublesome, and it is big with dimethyl suflfate toxicity,
For operator than relatively hazardous.
Summary of the invention
At high cost in the prior art the purpose of the present invention is overcoming, the big deficiency of reagent toxicity provides a kind of at low cost, receipts
The synthetic method for the 4- chloromethyl pyridine hydrochloride that rate is high, reaction condition is mild.
A kind of synthetic method of 4- chloromethyl pyridine hydrochloride provided by the invention, preparation method the following steps are included:
(1) it using 4- picoline as raw material, with water as solvent, is oxidized with potassium permanganate as Isonicotinic acid, wherein
The molar ratio of 4- picoline and potassium permanganate is 1:2.1-2.3, and oxidizing temperature is 75-80 DEG C, heats 35min, fully reacting
Reaction solution is adjusted to acidity, then cold filtration obtains Isonicotinic acid；
(2) Isonicotinic acid and methanol generate Isonicotinic acid methyl esters in acid condition, wherein Isonicotinic acid and first
The molar ratio of alcohol is 1:1.3；
(3) reduction Isonicotinic acid methyl esters is 4- pyridinemethanol；
(4) 4- pyridinemethanol reacts to obtain purpose product 4- chloromethyl pyridine hydrochloride, 4- pyridinemethanol with thionyl chloride
Molar ratio with thionyl chloride is 1:1.1-1.3.
Further, potassium permanganate is added portionwise under conditions of 80 DEG C in the step (1).
Further, pH adjusting is that the pH value of reaction solution is adjusted to 3-4 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, the Isonicotinic acid methyl esters and boron hydrogen
The molar ratio for changing sodium is 1:4-5, reduction reaction Lewis acid as catalyst.
Further, the Lewis acid is alchlor.
Further, the solvent that the reduction reaction uses is that be that 1:1 is mixed with THF and toluene with volume ratio mixed
Bonding solvent.
The reaction equation of the method for the present invention are as follows:
Be using the beneficial effect of technical solution of the present invention: reaction step is few, at low cost, purity is high, high income, operation
Safety, the method for the present invention are suitble to large-scale industrial production.
Specific embodiment
In order to which the present invention is further explained, some embodiments are given 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) 4- picoline (18.6g, 0.2mol) being added in the flask of 250ml, water 150ml is heated to 80 DEG C, point
It criticizes and potassium permanganate (66.36g, 0.42mol) is added, maintain temperature in 75-80 DEG C of heating stirring 35min, thin-layer chromatography tracking point
Analysis, is adjusted to 3 for the pH value of reaction solution with the hydrochloric acid of 2mol/l to fully reacting, and reacting liquid temperature is cooled to 25 DEG C of suction filtration systems
Obtain Isonicotinic acid.
(2) Isonicotinic acid and methanol (12g, 0.26mol) generate Isonicotinic acid methyl esters under concentrated sulfuric acid effect.
(3) Isonicotinic acid methyl esters is dissolved in the solvent that 75mlTHF and 75ml toluene mixes, and 0-5 DEG C adds in batches
Enter sodium borohydride (30.24g, 0.8mol) and alchlor, the 3-4h that adds that the reaction was continued, thin-layer chromatography trace analysis is to having reacted
It is complete to obtain 4- pyridinemethanol.
(4) after 4- pyridinemethanol in methanol solution with thionyl chloride (26.18g, 0.22mol) react, thin-layer chromatography with
Track analysis, stops reaction after reacting and being completely converted into 4- chloromethyl pyridine hydrochloride, filters, obtains product 26.2g, yield is
80% (molar yield).
Embodiment 2
(1) 4- picoline (18.6g, 0.2mol) being added in the flask of 250ml, water 150ml is heated to 80 DEG C, point
It criticizes and potassium permanganate (69.5g, 0.44mol) is added, maintain temperature in 75-80 DEG C of heating stirring 35min, thin-layer chromatography tracking point
Analysis, is adjusted to 4 for the pH value of reaction solution with the hydrochloric acid of 2mol/l to fully reacting, and reacting liquid temperature is cooled to 25 DEG C of suction filtration systems
Obtain Isonicotinic acid.
(2) Isonicotinic acid and methanol (12g, 0.26mol) generate Isonicotinic acid methyl esters under concentrated sulfuric acid effect.
(3) Isonicotinic acid methyl esters is dissolved in the solvent that 75mlTHF and 75ml toluene mixes, and 0-5 DEG C adds in batches
Enter sodium borohydride (34g, 0.9mol) and alchlor, add that the reaction was continued 3-4h, thin-layer chromatography trace analysis to fully reacting
Obtain 4- pyridinemethanol.
(4) after 4- pyridinemethanol in methanol solution with thionyl chloride (26.18g, 0.22mol) react, thin-layer chromatography with
Track analysis, stops reaction after reacting and being completely converted into 4- chloromethyl pyridine hydrochloride, filters, obtains product 26.9g, yield is
82% (molar yield).
Embodiment 3
(1) 4- picoline (18.6g, 0.2mol) being added in the flask of 250ml, water 150ml is heated to 80 DEG C, point
It criticizes and potassium permanganate (72.7g, 0.46mol) is added, maintain temperature in 75-80 DEG C of heating stirring 35min, thin-layer chromatography tracking point
Analysis, is adjusted to 4 for the pH value of reaction solution with the hydrochloric acid of 2mol/l to fully reacting, and reacting liquid temperature is cooled to 25 DEG C of suction filtration systems
Obtain Isonicotinic acid.
(2) Isonicotinic acid and methanol (12g, 0.26mol) generate Isonicotinic acid methyl esters under concentrated sulfuric acid effect.
(3) Isonicotinic acid methyl esters is dissolved in the solvent that 75mlTHF and 75ml toluene mixes, and 0-5 DEG C adds in batches
Enter sodium borohydride (37.8g, 1.0mol) and alchlor, the 3-4h that adds that the reaction was continued, thin-layer chromatography trace analysis is to having reacted
It is complete to obtain 4- pyridinemethanol.
(4) after 4- pyridinemethanol in methanol solution with thionyl chloride (26.18g, 0.22mol) react, thin-layer chromatography with
Track analysis, stops reaction after reacting and being completely converted into 4- chloromethyl pyridine hydrochloride, filters, obtains product 25.6g, yield 78%
(molar yield).
Claims (7)
1. a kind of synthetic method of 4- chloromethyl pyridine hydrochloride, it is characterised in that method includes the following steps:
(1) it using 4- picoline as raw material, with water as solvent, is oxidized with potassium permanganate as Isonicotinic acid, wherein 4- first
The molar ratio of yl pyridines and potassium permanganate is 1:2.1-2.3, and oxidizing temperature is 75-80 DEG C, heats 35min, fully reacting will be anti-
Liquid is answered to be adjusted to acidity, then cold filtration obtains Isonicotinic acid；
(2) Isonicotinic acid and methanol generate Isonicotinic acid methyl esters in acid condition, wherein Isonicotinic acid and methanol
Molar ratio is 1:1.3；
(3) reduction Isonicotinic acid methyl esters is 4- pyridinemethanol；
(4) 4- pyridinemethanol reacts to obtain purpose product 4- chloromethyl pyridine hydrochloride, 4- pyridinemethanol and chlorine with thionyl chloride
The molar ratio for changing sulfoxide is 1:1.1-1.3.
2. a kind of synthetic method of 4- chloromethyl pyridine hydrochloride according to claim 1, it is characterised in that: the step
(1) potassium permanganate is added portionwise under conditions of 80 DEG C in.
3. a kind of synthetic method of 4- chloromethyl pyridine hydrochloride according to claim 1, it is characterised in that: the step
(1) pH adjusting is that the pH value of reaction solution is adjusted to 3-4 with the hydrochloric acid of 2mol/l in.
4. a kind of synthetic method of 4- chloromethyl pyridine hydrochloride according to claim 1, it is characterised in that: the step
(1) temperature of cold filtration is 25 DEG C in.
5. a kind of synthetic method of 4- chloromethyl pyridine hydrochloride according to claim 1, it is characterised in that: the step
(3) reducing agent used in is sodium borohydride, and the molar ratio of the Isonicotinic acid methyl esters and sodium borohydride is 1:4-5, described
Reduction reaction Lewis acid as catalyst.
6. a kind of synthetic method of 4- chloromethyl pyridine hydrochloride according to claim 5, it is characterised in that: described
Lewis acid is alchlor.
7. a kind of synthetic method of 4- chloromethyl pyridine hydrochloride according to claim 5, it is characterised in that: the reduction
It with volume ratio is mixed solvent that 1:1 is mixed that react the solvent that uses, which be with THF and toluene,.
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| CN201711095832.6A CN109761888A (en) | 2017-11-09 | 2017-11-09 | A kind of synthetic method of 4- chloromethyl pyridine hydrochloride |
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| CN201711095832.6A CN109761888A (en) | 2017-11-09 | 2017-11-09 | A kind of synthetic method of 4- chloromethyl pyridine hydrochloride |
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| CN201711095832.6A Withdrawn CN109761888A (en) | 2017-11-09 | 2017-11-09 | A kind of synthetic method of 4- chloromethyl pyridine hydrochloride |
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2017
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Application publication date: 20190517 |
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