CN1631881A

CN1631881A - Process for synthesizing 2-chloro-5-chloromethylpyridine

Info

Publication number: CN1631881A
Application number: CN 200310121181
Authority: CN
Inventors: 张伟; 徐杰
Original assignee: Dalian Institute of Chemical Physics of CAS
Current assignee: Dalian Institute of Chemical Physics of CAS
Priority date: 2003-12-22
Filing date: 2003-12-22
Publication date: 2005-06-29

Abstract

A method for synthesizing 2-chlorine-5-chloromethyl pyridine, uses 2-chlorine-5- as the raw material, organic chloride as solvent, in the conditions of temperature:80-180deg.C and normal pressure, initiate by chloride or light, through choosing chlorination reaction to synthesize 2-chlorine -5-chloromethyl pyridine directly. The invention has high conversion rate and utilization ratio of raw material little coking in chlorination reaction, and high seletivity and productivity.

Description

The method of a kind of Synthetic 2-chloro-5-chloromethylpyridine

Technical field

The present invention relates to the preparation of Halogen, heterocycle organic intermediate, providing a kind of especially is raw material Synthetic 2-chloro-5-chloromethylpyridine chlorination method of (being called for short CCMP) with 2-chloro-5-picoline (being called for short CMP).

Background technology

2-chloro-5-chloromethylpyridine is a kind of important chloride, heterocycle organic intermediate, in field of fine chemical such as agricultural chemicals, medicine purposes is widely arranged.Traditional synthesis technique is to obtain by the chlorination of 2-chloro-5-picoline; But because selectivity is difficult to control, make that conversion of raw material and effective rate of utilization are lower, the chlorination selectivity is not high, and the actually operating difficulty.

USP 5,198, and 549 have introduced the method for a kind of 2-chloro-5-picoline selective chlorination Synthetic 2-chloro-5-chloromethylpyridine, and acetonitrile is a solvent.When with the Diisopropyl azodicarboxylate initiation reaction, be 47% 85 ℃ of following conversion of raw material, the yield of 2-chloro-5-chloromethylpyridine is 37%; When adopting UV-light to cause, feed stock conversion reaches 54%, and the yield of 2-chloro-5-chloromethylpyridine is 37%; The transformation efficiency of this method and yield are all lower.

It is raw material with 2-chloro-5-picoline that patent CN 00 1 22987.7 has introduced a kind of, the complete chlorating method of side chain, the feed stock conversion of this method up to 99.3%, side chain chlorination selectivity is 90.4%; Though this method has very high transformation efficiency and yield, the product that generates is the complete chlorizate 2-of a branched chain methyl chloro-5-nitrapyrin.

Usually, the side chain selective chlorination process of picoline analog derivative is attended by the side reaction of number of different types: as chlorination reaction on the pyridine ring, the excessive chlorination reaction of side chain, the HCl and the pyridine derivate reaction that are produced by chlorination process generate reactant salt, and between the various derivative dissimilar coking process etc. take place.These side reactions, especially coking not only can cause a large amount of wastes and the waste pollution of main raw material, and cause line clogging and discharging difficulty, make experiment or industrial operation become very complicated.

Summary of the invention

The object of the present invention is to provide the method for a kind of Synthetic 2-chloro-5-chloromethylpyridine, this method raw material availability height, coking are few, can high yield and highly selective Synthetic 2-chloro-5-chloromethylpyridine.

For achieving the above object, the method of Synthetic 2 provided by the invention-chloro-5-chloromethylpyridine is a raw material with 2-chloro-5-picoline, under organic solvent and chlorine existence condition, cause a step direct chlorination Synthetic 2-chloro-5-chloromethylpyridine by illumination or initiator.

The chlorination temperature scope of 2-chloro-5-picoline is 50-200 ℃, and more favourable temperature range is 80-180 ℃, and best temperature range is 100-150 ℃.Chlorination temperature is crossed when hanging down, and speed is slow; The chlorating by product increases on the pyridine ring.Temperature raises, and can accelerate chlorination reaction, and too high chlorination temperature increases energy consumption, and operation easier increases, and also can cause other side reactions such as coking or the excessive chlorination of side chain, reduces the selectivity of reaction.When adopting initiator to cause, the selection of chlorination temperature also need be considered the decomposition temperature of used initiator.

When chlorination reaction adopted initiator to cause, used initiator can be organic compound initiators such as benzoyl peroxide, Diisopropyl azodicarboxylate, azo two isocapronitriles, also no organic initiators such as Potassium Persulphate, ammonium persulfate.The charging capacity of initiator is 0.01-0.50 times (wt.) of raw material 2-chloro-5-picoline, is preferably in 0.02-0.08 doubly between (wt.).The feed way of initiator is according to temperature of reaction that adopts and initiator type decision; Can adopt intermittent type directly to feed intake; Also initiator can be mixed the continuous dropping mode in making beating back feeds intake with organic solvent; Preferably adopt initiator and the solvent continuous dropping mode of pulling an oar to feed intake, especially when the decomposition of initiator temperature of selecting for use is lower than temperature of reaction, making beating dropping mode can be avoided the quick decomposition of initiator or reinforced inhomogeneous.

When chlorination reaction adopted optical radiation to cause, the wavelength of used light source was preferably between the 270-480nm in the 190-700nm scope.The wavelength of light source is during greater than 480nm, and efficiency of initiation is low, photochemical dissociation reaction difficulty.

The organic solvent of chlorination process can be that chlorobenzene, dichlorobenzene, trichlorobenzene, oil of mirbane etc. are difficult to take place the chlorating aromatics, also can be aliphatic halogenated hydrocarbons such as methylene dichloride, ethylene dichloride, trichloromethane, trichloroethane, tetracol phenixin.Preferably boiling point surpasses the aromatic series chlorine-containing compound of temperature of reaction, and avoiding the vaporization losses of solvent in the reaction process, or because the partial vapor pressure of solvent causes higher working pressure.The charging capacity of organic solvent is many more, and is favourable more to the selectivity of chlorination reaction.Consider actually operating and running cost, the charging capacity of organic solvent is 0.1-10.0 times (wt.) of raw material 2-chloro-5-picoline, is preferably in 0.5-5.0 doubly between (wt.); When the charging capacity of organic solvent is very few, stop the DeGrain of coking and inhibition side reaction; When the charging capacity of organic solvent was excessive, the cost of later separation increased.As the buffer medium of chlorination reaction, the effect of organic solvent in chlorination process is: the temperature of reaction that can provide and guarantee to require, and make main reaction comparatively steady, side reaction reduces; Or production concentration in the reduction reaction system, the chlorination reaction product can effectively be disperseed; Or play the polymerization coking effect that stops raw material, intermediate and product.

Embodiment

Embodiment 1: with 110 gram 2-chloro-5-picolines (0.862mol) and 174 grams 1, the 2-dichlorobenzene joins in the chlorination reaction still of 500ml, is warmed up to 130 ℃, feeds chlorine; Per hour add the initiator Diisopropyl azodicarboxylate one time, add 0.3 gram at every turn, add altogether 4 times; Reaction is 4 hours under this temperature.Reaction is closed chlorine after finishing, and cooling was switched nitrogen replacement 0.5 hour, and it is 9～10 that adding sodium hydroxide is neutralized to pH value, tells water, and underpressure distillation separates solvent 1,2-dichlorobenzene.The amount that the rectifying of still liquid is got CCMP is 0.405mol, the CMP transformation efficiency is 56.1%, and the yield of CCMP (in the CMP that has transformed) is 83.9%.

Embodiment 2: with 110 gram 2-chloro-5-picolines (0.862mol) and 174 grams 1, the 2-dichlorobenzene joins in the chlorination reaction still of 500ml, is warmed up to 100 ℃, feeds chlorine; Per hour add the initiator Diisopropyl azodicarboxylate one time, add 0.6 gram at every turn, add altogether 4 times; Reaction is 4 hours under this temperature.Aftertreatment with embodiment 1 the amount of CCMP is 0.301mol, the CMP transformation efficiency is 39.0%, the yield of CCMP (in the CMP that has transformed) is 89.5%.

Embodiment 3: with 110 gram 2-chloro-5-picolines (0.862mol) and 174 grams 1, the 2-dichlorobenzene joins in the chlorination reaction still of 500ml, is warmed up to 150 ℃, feeds chlorine; Per hour add the initiator Diisopropyl azodicarboxylate one time, add 0.6 gram at every turn, add altogether 4 times; Reaction is 4 hours under this temperature.Aftertreatment with embodiment 1 the amount of CCMP is 0.419mol, the CMP transformation efficiency is 65.0%, the yield of CCMP (in the CMP that has transformed) is 74.8%.

Embodiment 4: with 110 gram 2-chloro-5-picolines (0.862mol) and 348 grams 1, the 2-dichlorobenzene joins in the chlorination reaction still of 500ml, is warmed up to 130 ℃, feeds chlorine reaction.Other condition and aftertreatment with embodiment 1 the amount of CCMP is 0.391mol, the CMP transformation efficiency is 54.6.0%, the yield of CCMP (in the CMP that has transformed) is 86.7%.

Embodiment 5: with 110 gram 2-chloro-5-picolines (0.862mol) and 174 grams 1,2, the 4-trichlorobenzene joins in the chlorination reaction still of 500ml, is warmed up to 130 ℃, logical chlorine reaction.Other condition and aftertreatment with embodiment 1 the amount of CCMP is 0.412mol, the CMP transformation efficiency is 57.3%, the yield of CCMP (in the CMP that has transformed) is 83.4%.

Embodiment 6: 110 gram 2-chloro-5-picolines (0.862mol) and 174 gram tetracol phenixin are joined in the chlorination reaction still of 500ml, be warmed up to 80 ℃, logical chlorine back flow reaction.Other condition and aftertreatment with embodiment 1 the amount of CCMP is 0.042mol, the CMP transformation efficiency is 6.4%, the yield of CCMP (in the CMP that has transformed) is 76.3%.

Embodiment 7: with 110 gram 2-chloro-5-picolines (0.862mol) and 174 grams 1,2, the 4-trichlorobenzene joins in the chlorination reaction still of 500ml, is warmed up to 130 ℃, logical chlorine reaction.Per hour add initiator azo two isocapronitriles one time, add 0.3 gram at every turn, add altogether 4 times.Other condition and aftertreatment with embodiment 1 the amount of CCMP is 0.360mol, the CMP transformation efficiency is 50.2%, the yield of CCMP (in the CMP that has transformed) is 83.1%.

Embodiment 8: with 110 gram 2-chloro-5-picolines (0.862mol) and 174 grams 1, the 2-dichlorobenzene joins in the chlorination reaction still of 500ml, is warmed up to 130 ℃, feeds chlorine; Use UV-light (wavelength 300nm) irradiation reaction system to cause means as free radical.Reaction is 4 hours under this temperature.Other condition and aftertreatment with embodiment 1 the amount of CCMP is 0.310mol, the CMP transformation efficiency is 46.30%, the yield of CCMP (in the CMP that has transformed) is 78.2%.

Claims

1, the method for a kind of Synthetic 2-chloro-5-chloromethylpyridine, with 2-chloro-5-picoline is raw material, add raw material weight 0.1-10 organic solvent doubly, feed chlorine in 50-200 ℃, add raw material weight 0.01-0.5 initiator doubly, normal pressure reacted 2-6 hour down, and underpressure distillation separates solvent, and the rectifying of still liquid is got target product;

Described organic solvent is aromatic series chlorine-containing compound or the aliphatic halogenated hydrocarbon that boiling point surpasses temperature of reaction;

Described initiator is benzoyl peroxide, Diisopropyl azodicarboxylate, azo two isocapronitriles, Potassium Persulphate or ammonium persulfate.

2, the method for claim 1 is characterized in that, the add-on of described initiator is 0.02-0.08 a times of raw material weight.

3, the method for claim 1 is characterized in that, described initiator is to mix continuous dropping the in making beating back to feed intake with organic solvent.

4, the method for a kind of Synthetic 2-chloro-5-chloromethylpyridine, with 2-chloro-5-picoline is raw material, add raw material weight 0.1-10 organic solvent doubly, feed chlorine in 50-200 ℃, adopting wavelength is that the 190-700nm light width of cloth was penetrated the initiation chlorination reaction 2-6 hour, underpressure distillation separates solvent, and the rectifying of still liquid is got target product;

Described organic solvent is aromatic series chlorine-containing compound or the aliphatic halogenated hydrocarbon that boiling point surpasses temperature of reaction.

5, method as claimed in claim 4 is characterized in that, the optical source wavelength that causes chlorination reaction is 270-480nm.

As claim 1 or 4 described methods, it is characterized in that 6, described temperature of reaction is 80 ℃-150 ℃.

As claim 1 or 4 described methods, it is characterized in that 7, described organic solvent is chlorobenzene, dichlorobenzene, trichlorobenzene, ethylene dichloride, trichloroethane or tetracol phenixin.

As claim 1 or 4 described methods, it is characterized in that 8, the add-on of described organic solvent is 0.5-5.0 a times of raw material weight.