CN105906570A - Synthesis technology of 4,6-dichloropyrimidine - Google Patents

Abstract

The invention provides a synthesis technology of 4,6-dichloropyrimidine. The synthesis technology comprises the following steps of (1) adding 4,6-dihydroxypyrimidine and a pyridine catalyst into a reaction kettle, adding a trichloromethane solvent, sufficiently stirring, starting jacket steam, and increasing the temperature; (2) after the temperature in the reaction kettle is stabilized to 50 DEG C, filling light and gas to react, filling nitrogen to remove gas after the reaction is completed, and enabling an adsorbing tower to adsorb tail gas; (3) separating water from the generated matter, transferring the solution after water separating into an extraction kettle using ethanol as an extraction agent, performing vacuum distillation on the extracted solution, and recovering the pyridine catalyst; (4) washing the solid extracting matter by washing, sucking and filtering, and recrystallizing, so as to obtain the white needle-shaped product of 4,6-dichloropyrimidine. Compared with the prior art, the synthesis technology has the advantages that the pollution to environments by waste water and waste gas is avoided, the raw material can be recycled, and the cost is reduced.

Description

A kind of synthesis technique of 4,6-dichloro pyrimidine

Technical field:

The present invention relates to 4,6-dichloro pyrimidine production field, it is specifically related to a kind of 4,6-dichloro pyrimidine Synthesis technique.

Background technology:

4,6-dichloro pyrimidine is widely used in the synthesis of pyrimidines.4,6-bis- Chloropyrimide is also the important intermediate of synthesizing antitumor medicine fluorouracil, and fluorouracil belongs to anti-generation Thank to antineoplastic agent, the most clinically as a line or the two wires medication of antineoplaston, the most right Entity tumor has good therapeutic effect.Fluorouracil can suppress thymidylic acid to synthesize Enzyme, blocks deoxyribonucleotides nucleotide and is converted into thymidylic acid, interference DNA synthesis. Synthesis to RNA also has certain inhibitory action.Individually or it is united and applied in other drug Breast carcinoma and gastroenteric tumor auxiliary surgical help treatment, are also used for the aunt of some No operation malignant tumor Breath treatment, especially those gastrointestinal tract, mammary gland, incidence, liver, urinary system and pancreas Malignant tumor.Chemist is devoted to the chemical modification work to fluorouracil always for many years Making, the particularly targeting derivant research to fluorouracil, by the modification to structure, fluorine is urinated The pyrimidine specific transport of energy, to target cell or target organ, improves its targeting, reduces it serious Untoward reaction.

4,6-dichloro pyrimidines are the heterocycle compounds of a kind of Nitrogen element, are synthesis miazines One of important intermediate of compound, is widely used in medical product, pesticide miazines product Synthesis, the sulfa drugs such as sulfamonomethoxine, sulfamonomethoxine.Phonetic from 4,6-dichloro The application of pyridine it can be seen that market is to 4,6-dichloro pyrimidine and raw material 4 thereof, 6-dihydroxy-pyrimidine Demand can increase steadily, therefore should strengthen 4, the industrialized production of 6-dichloro pyrimidine.

At present the existing technique of synthesis 4,6 dichloro pyrimidines easily produces a large amount of waste water, waste gas and Phosphorous by-product, easily causes the pollution of environment, and existing complex process, is not suitable for industrialization Produce.

Summary of the invention:

For problem present in above technology, the invention provides a kind of 4,6-dichloro pyrimidine Synthesis technique, both can avoid the pollution to environment of waste water, waste gas, it is also possible to make raw materials recovery Utilize, reduce cost.

The present invention is achieved by the following technical solutions:

A kind of 4, the synthesis technique of 6-dichloro pyrimidine, described technique comprises the following steps:

(1) in reactor, add 4,6-dihydroxy-pyrimidine and 0.5 weight portion of 1 weight portion Pyridine catalyst, be simultaneously introduced solvent chloroform, turn on agitator is stirred, stirring After Chong Fen, it is then turned on jacket steam and makes reactor temperature raise；

(2) question response temperature in the kettle is stable is passed through phosgene carries out phosgenation reaction when 50 DEG C, After reaction completely, being passed through nitrogen and carry out catching up with gas in reactor, tail gas is entered by pipeline and inhales simultaneously Receipts tower absorbs；

(3) product in step 2 being carried out a point water, the solution after point water is transferred to second Alcohol is in the extraction kettle of extractant, the solution after extraction is carried out rectification under vacuum, reclaims capable of circulation The pyridine catalyst utilized；

(5) after washing, sucking filtration, recrystallization, white is obtained to the solid phase extraction thing of step 3 Needle-like product 4,6-dichloro pyrimidine.

The invention have the benefit that and carry out reaction by employing phosgene to obtain product 4,6-dichloro phonetic Pyridine, it is to avoid traditional handicraft uses containing phosphorous oxides, it is to avoid the phosphorus of environment pollutes；With Time by the absorption of tail gas process prevent the atmospheric pollution caused and the threat to human health； Production technology is fairly simple, by recycling design and catalyst, both can avoid contaminated wastewater, Also achieve the recycling of raw material simultaneously, reduce cost.

Detailed description of the invention:

Below in conjunction with detailed description of the invention, the present invention is described in further details.

The invention provides a kind of 4, the synthesis technique of 6-dichloro pyrimidine, technique mainly includes following Step: add the 4,6-dihydroxy-pyrimidine of 1 weight portion and 0.5 weight portion in reactor Pyridine catalyst, is simultaneously introduced solvent chloroform, and turn on agitator is stirred, and stirring is filled After Fen, open jacket steam and make reactor temperature raise；Question response temperature in the kettle is stablized When 50 DEG C, it is passed through phosgene and carries out phosgenation reaction, after reaction completely, in reactor, be passed through nitrogen Gas carries out catching up with gas, and tail gas is entered absorption tower by pipeline and absorbs simultaneously, it is to avoid the pollution of air； Product in reactor is carried out a point water, waste water and product can be efficiently separated, The solution after water is divided to transfer in the extraction kettle with ethanol as extractant, can be by catalyst pyridine Separate with product, the solution after extraction is carried out rectification under vacuum, reclaim pyridine catalyst, permissible Recycle, cost-effective；Again solid phase extraction thing is obtained after washing, sucking filtration, recrystallization White needles product 4,6-dichloro pyrimidine, production needed raw material phosgene is self-produced former in being factory simultaneously Material.

The present invention obtain 4, the yield of 6-dichloro pyrimidine is 80%, and not only product yield is higher, The process that the present invention provides simultaneously does not pollutes the environment, moreover it is possible to effectively save cost.

Claims (1)

1. one kind 4, the synthesis technique of 6-dichloro pyrimidine, it is characterised in that described synthesis work Skill comprises the following steps:

(1) in reactor, add 4,6-dihydroxy-pyrimidine and 0.5 weight portion of 1 weight portion Pyridine catalyst, be simultaneously introduced solvent chloroform, turn on agitator is stirred, stirring After Chong Fen, it is then turned on jacket steam and makes reactor temperature raise；

(2) question response temperature in the kettle is stable is passed through phosgene carries out phosgenation reaction when 50 DEG C, After reaction completely, being passed through nitrogen and carry out catching up with gas in reactor, tail gas is entered by pipeline and inhales simultaneously Receipts tower absorbs；

(3) product in step 2 being carried out a point water, the solution after point water is transferred to second Alcohol is in the extraction kettle of extractant, the solution after extraction is carried out rectification under vacuum, reclaims capable of circulation The pyridine catalyst utilized；

(4) after washing, sucking filtration, recrystallization, white is obtained to the solid phase extraction thing of step 3 Needle-like product 4,6-dichloro pyrimidine.