SU576045A3 - Method of preparing pyrimidine derivatives - Google Patents

Description

(54) METHOD FOR PRODUCING PYRIMIDINE DERIVATIVES

one

The invention relates to a new method of producing new compounds, derivatives of pyrimi, dina, which can be used in agriculture as fungicides,

In the chemistry of pyrimidines, the reaction of the dehalogenation of chloropyrimidines by catalytic hydrogenation is known. Palladium on carbon is used as a catalyst; hydrogenation is carried out at room temperature and atmospheric pressure.

The proposed method of comparing pyrimidine derivatives of the general formula

where Q is chlorine or fluorine; p - 1-5, is that the compound of formula

n x

N

with-//

VX

N

Op

where X is hydrogen, chlorine, bromine, iodine, and, at least, one and :) X is chlorine or bromine, or iodine,

n have the above meanings, are treated with hydrogen over René nickel under a pressure of -7 atm in methanol in the presence of a hydrogen halide acceptor at; 20-60 ° C followed by separation of the target product in a known manner.

Of the hydrogen halide acceptors, amines can be used that are substituted by 1-3 Cj-C4 alkyl, potassium or sodium acetate, preferably triethylamine.

Hydrogen halide acceptor ber): in 5% S excess of metric one.

The catalyst used must be sufficiently active and selective in the reactive dehalation of the pyrimidine ring (the benzene ring should not be affected), B. René’s nickel is used as such a catalyst.

Nick; pbne, supplied as a suspension in water with a high pH value, before use, washed, for example, with thanol or ethanol to remove water and reduce its basicity (Rene nickel was thoroughly mixed with ethanol, aged} 1% For an hour, the lactate is removed, the fresh eganol is added and re-mixed, often this process is repeated) and stored in methanol and ethanol. The amount of the loaded catalyst does not have a significant value. Typically, the amount of catalyst is 5-10% or slightly more by weight of the degradable substance. Further increase the amount of catalyst tolyso increases the cost of the process. The reaction is selectively carried out in a low-pressure hydrogenation apparatus, for example, a Charle apparatus, under a hydrogen pressure of 1-7 at. At a higher pressure, complete dehydration and / or destruction of the pyrimidine ring occurs instead of selective dehydration of the latter. The reaction temperature is 20-60 ° С, П1Ж temperature higher than 60 ° С 1 mtk11lly dehydration is observed rather than selective dehalogenation of the pyrthidine ring - reaction time 2-16, preferably S-6 h. . Over the course of the reaction, it is possible to follow the change in the hydrogen pressure in the hydrogenation apparatus. At the end of the reaction, the catalyst is filtered off, washed with a solvent, and the product is isolated from the filtrate by the known methods. The starting compounds to be dehalogenated, where X is chlorine or bromine in position 2 and 4 {srimidine ring, can be obtained by reacting pyrimidinone or uracil with dkphenylmethane, which is replaced by chlorine or fluorine, in glacial acetic acid in P1jestine boron boron trifluoride (elucent). catalizer {(followed by treatment with bromocoxine H 2 oxychloride. Starting compounds for degalovation, where X is bromine or chlorine in position 4 and 6 are midinch ic rings, by reacting the correspondingly substituted diphenylmethanol with mmo New ester followed by co-condensation with formamidine and treatment with bromide or chlorine phosphorus. Compounds in which X is bromine or chlorine in positions 2, 4 and 6 of the pyrimidine ring are easily obtained via malonic ether (see above), followed by condensation of malonic ether with urea and the treatment of 2,4,6 -nrimidine trion with omoxanes H-phosphorus oxychloride. EXAMPLE 1. To a mixture of 84 g (0.75 mol) of uracil and 250 MP of acetic acid and 37.5 g of trifluoride boron was added 189.7 g (0.75 mol) 2.4 dichlorobenzhydrol and refluxed for 1 hour, added 50 cpx glacial acetic acid. 2 hours after heating at boiling point, a further south of boron trifluoride is introduced. After heating at boiling point for 3 hours, 25 ml of acetic acid and south of benzhydrol are added. After 5 hours, the South Beisprol was added, 25 ml of acetic acid and 10 g of Tr lOx of boron, nocife heating was stopped for 7 hours, the reaction mixture was filtered, the filtrate was poured onto ice, stirred, the precipitate was filtered off, washed twice with ether and 170.4 g were obtained (65%) 2,4 - dioxy - 5 - (2,4 - dkhlorbenzgid {zl) - pyrimidine, t.cl. 302 - 306 ° C. 70 g of 2,4 - dioxy 5 - (2,4-dichlorobenzhydryl) -pirtmidine and 10 g of dimethylformamide are added to a mixture of 400 g of phosphorus chloro-kish and 10 g of dimethylformamide, heated up for 1 hour at a temperature of Kinpium, and an excess of phosphorus oxychloride is detected. Dissolve the reaction mixture with stirring on ice and extract with ether. The combined extracts are washed with cold heat, evaporated, the residue is recrystallized from isopropanol and 38.7 g of 2.4 - dichloro - 5 - (2.4 - dichlorobenzdzdryl) - pyrimidine are obtained, mp. 114 - 115 ° C. . PRI mme R 2. A mixture of 5D g (0.05 mol) of malonamide, 20 ml of 98 - 1Cy% o1 avium acid, 12.7 g (0.05 mol) of 2.4 - dichlorobenzhydrol and 5 g of trifluoride boron is boiled for 10–15 min with a reflux cooler, poured into water, the precipitate is filtered off, pressed into water, and 9.4 g (55.6%) of 2.4 dichlorobenehydrylmalonamide are obtained (according to elemental analysis and NMR spectroscopy) tsh1 279 - 283 ° С, which is used further without additional purification. A mixture of 16.9 g (0.05 mol) of 2,4-dichlorobenzhydrylmalonamide, 60 ml of formamide, 60 ml of dimethyl sulfoxide and 6 g of sodium metllate is heated to 125 ° C, kept at 12 ° C for 1 hour and 1 g of sodium methoxide is added. 1 g of 1 "tilate is added hourly until 7 g of sodium metclate is added. It is heated for another 7 hours (only 15 hours), poured into water, filtered, a small amount of an insoluble material is separated, the filtrate is acidified with methylated hydrochloric acids (the precipitate is filtered off, washed with water and ether, dried under vacuum and according to elemental analysis and NMR 4,6 - diox - 5 - (2,4 dichlorobenzhydryl) - pyrimidine, T.PL 285 - 288 ° C, a mixture of 10 g (28.8 mol), 4,6 - dioxy - 5 - (2,4 dichlorobenzhydryl ) - pyrimidia and 90 ml of phosphorus oxychloride are boiled in a 250 ml round-bottomed flask with a reflux condenser, the excess is distilled phosphorus oxychloride, mixed into ice-chloroform, alkalized (pH 8) with solid soda, the organic layer is separated, washed with a saturated aqueous solution of sodium bicarbonate and water, dried, filtered, the filtrate is evaporated under vacuum, and an amber color layer is obtained, which k1 is installed ( when scratching the walls), forming a straw yellow powder of pn added pentane. The powder is filtered off (8.8 g), recrystallized from isopropanol and a crystalline 4.6 dcchlor - 5 - (2.4 dichlorobenzgdryl) - pyrimidine is obtained, mp. 138 - 139 ° С, with a yield of 70%. . Froze A mixture of 3.8 g (0.01 mol) and 4.6 dichloro - 5 - (2.4 - dichlorobenegidryl); .. pyrimidium, 100 ml of methanol, 2.2 g of triethylamine and 8 g of Rene nickel are treated with hydrogen in a Paar apparatus (flask 500 ml) at room temperature and an initial pressure of 41 psi (1F / KV.DYUK 63.48 g / cm). After 13.5 hours (a little more hydrogen is consumed than the theory follows), the reaction is stopped, the catalyst is filtered off, washed well with methanol, the filtrate is spun out under vacuum to remove methanol, the remaining gummy substance is dissolved in ether, washed with water, the aqueous layer is separated, Extraction is carried out twice with ether, the combined ethyl sulfate extracts, together with the first ether layer, are washed again with water, dissolved over sodium sulfate, filtered and distilled first under atmospheric pressure and then under vacuum. The residue (2.8 g, or 90.4%) is analyzed by vapor chromatography, it contains 96% a t (2.4 dichlorophenyl) - a - phenyl - 5 - pyrimidylmethane.

PRI me R 4. A mixture of 3.8 g (0.01 mol) 2,4-dkhlor S - (2,4 - dichlorobenz pdryl) - pyrimidine, 95 MP of methanol, 2.2 g of triegylamine and 4 g of washed nickel Re in hydrogen treatment (initial pressure 45 psi) in a Pari apparatus (500 MI glass) at room temperature. Within 2 hours, the hydrogen pressure is leveled and the spinning 1 is closed. aprtsklnuyu mixture flrutru, catalyst well prokshvayut methanol, take up the filtrate under vacuum, about the residue, as in 1F 3, they produce a - (2.4 dichlorophenyl) - and fatl 5, - pyrimidylmethane, yield 95%, purity 90% (according to vapor phase (rafni).

Claims (2)

Invention Formula The method of obtaining the pyrimidine salt of the general formula where Q is chlorine or fluorine; P - 1-5, characterized in that the compound is abraham of the formula H X / y. Otn VN 6 where X is hydrogen, chlorine, bromine, iodine, and at least one of X is chlorine or bromine, or iodine; Q and p have the above values, are subjected to the action of hydrogen over Rene nickel under a pressure of 1-7 atm in methanol in the presence of a hydrogen acceptor at X) -60 ° C, followed by separation of the product in a known manner. 2. A method according to claim I, characterized in that t-trapsamine is used as a hydrogen halide acceptor.