IE48342B1

IE48342B1 - New preparation process of 2-chloro pyrimidine

Info

Publication number: IE48342B1
Application number: IE106779A
Authority: IE
Original assignee: Expansia Sa
Priority date: 1978-05-31
Filing date: 1979-08-08
Publication date: 1984-12-12
Also published as: IE791067L

Description

The present invention relates to an improved process for the preparation of 2-chloro pyrimidine.

This compound is already known but, so far, the processes used for its preparation are not very satisfactory, more particularly with respect to the yield.

One of these synthesis is described in Organic Syntheses, volume IV page 182 ; according to this method, the reaction is performed between -15°C and -10°C (use of a diazonium salt in the presence of hydrochloric acid); the yield is always lower than %. A slight improvement of this process has been later described by KRCHNAK U. et ARNOLD 1., Czechoslow. Chem. Commun. 40, 1390 (1975), with the use of a 5 M lithium chloride; nevertheless, the yield was lower than 50%. It has been noticed that if it was possible to increase the concentration in chloride ions, the yield might be significantly improved. After extensive investigations, it has been found that the suitable chlorides for this purpose were those of the transition metals and of tin, antimony, thallium and zinc.

The most favourable reaction conditions have been encountered by using zinc chloride, instead of the previously used lithium chloride, which rendered possible the reaction at a higher temperature than previously, with a correlative increase in the yield. Zinc chloride leads to an intermediate complex of better stability; it also presents a good solubility in the reaction mixture, is easy to recover and comparatively cheaper to use.

As to the solvents to be used, any non polar solvent with a low boiling point is suitable; very good results are obtained with methylene chloride.

More precisely, this invention relates to a process of preparation 5 of 2 - chloro - pyrimidine starting from 2 - amino - pyrimidine, hydrochloric acid and an alkali metal nitrite, the reactants being present in substantially the same proportions as in previously known methods, consisting of preparing a mixture of hydrochloric acid and a non-polar solvent of low boiling point and then introducing 2 · amino - pyrimidine, wherein a metal chloride selected from those of transition metals, tin antimony and zinc is added slowly at ambient temperature, the alkali metal nitrite is then introduced under an inert gas flow at a temperature not exceeding 10°C, and finally the reaction mixture is poured into iced water.

According to a preferred feature of the invention, the metal chloride is 15 zinc chloride.

According to another preferred feature of the invention, the non polar solvent is methylene chloride.

The invention will be better understood from the description of the following example : EXAMPLE: In a 250-1 iter reactor is prepared the mixture of 27 kg (approximately 265 mols) of concentrated hydrochloric acid (d = 1.18) and 35 kg -or 28 litres- of methylene chloride. There are thus added, under stirring, 8 kg (84.12 mols) of 2-amino pyrimidine which leads to a solution. After cooling, is added between 15 and 20°C, kg (242.5 mols) of zinc chloride; the addition is effected in about 4834-2 minutes and leads to a mustard-coloured suspension.

After a further cooling to 5 or 10°C and an introduction of a nitrogen flow, there are added (in three hours and a quarter) kilos (i.e. 145 mols) of sodium nitrite. There is an emission of nitrous vapours; 30 minutes after the end of this introduction, the reaction mixture is poured into 150-1itres of iced water and allowed to rest.

The organic phase is then separated and the aqueous phase is with treated 4 times / 50 kg (40 litres) of methylene chloride. All the 10 organic phases are gathered and dried on 3 kg of dry sodium sulphate, then filtered, concentrated at ordinary pressure at 45-50°C; this allows the recovery of about 80% of the methylene chloride.

The remaining organic phase is then concentrated in a rotary evaporator under reduced pressure (25 mm of Hg) at a temperature not exceeding 35°C, then dried for one and a half hours at 40°C.

There are obtained 6.6 kg (yield 69%) of 2-chloro-pyrimidine which is a yellowish crystalline powder melting at 63-65°C (Koffler), the analysis of which shows a perfect correspondence with the formula: W2C1·

Claims

1. A process of preparation of 2-chloro - pyrimidine starting from 2 - amino - pyrimidine, hydrochloric acid and an alkali metal nitrite, the reactants being present in substantially the same proportions as 5 in previously known methods, consisting of preparing a mixture of hydrochloric acid and a non-polar solvent of low boiling point and then introducing 2 - amino - pyrimidine, wherein a metal chloride selected from those of transition metals, tin, antimony and zinc is added slowly at ambient temperature, the alkali metal nitrite is then 10 introduced under an inert gas flow at a temperature not exceeding 10°C, and finally the reaction mixture is poured into iced water.

2. A process of preparation according to claim 1 in which the metal chloride is zinc chloride.

3. A process of preparation according to claim 1 or claim 2 in 15 which the non-polar solvent is methylene chloride.

4. A process for preparing 2-chioro-pyrimidine substantially as hereinbefore described with reference to the Example.

5. 2 - chloro-pyrimidine whenever prepared by the process claimed in any of the preceding claims.