DE1803167C - Process for the preparation of 5 chlorine 3,6 dialkyl uracilen - Google Patents

Description

Process for the preparation of 5-chloro-3,6-dialkyluracils.

It has been found that 5-ChIOr-B, 6-dialkyluracile the general formula

R ₁ - N N -Cl O H -R ₂

in which R _{1 is} an alkyl radical having 1 to 10 carbon atoms and R _{2 is} an alkyl radical having 1 to 3 carbon atoms, can be prepared in good yield by an aqueous solution of the sodium or potassium salt of a 3,6-dialkyluracil of the general formula

R ₁ -N

1
O

M ⁺

v-'orin R ₁ and R _{4 have} the aforementioned meaning and M ⁺ denotes a sodium or potassium ion, with an aqueous solution of sodium or potassium hypochlorite in a 0 to 40% stoichiometric excess at a temperature between -10 and +65 ⁰ C.

The aqueous Uracilsalzlösung at a concentration of 5 to 30 ° / _0, preferably from 10 brs 25% of free uracil with aqueous sodium or potassium chlorite with a concentration of 5 ° to 16 ° / o, to lO ° / o, preferably offset 6 . The excess of the solution of the hypochlorite depends on the temperature and the purity of the solution of the alkali salt of 3,6-dialkylenuracils and is preferably 5 to 35 ° / _0th Smaller excesses can be used at lower temperatures.

The Alkalihypochloritzusatz to the mixture takes place over a period of 5 to 180 minutes, preferably 5 to 30 minutes while the temperature in the respectively required dimensions by external cooling between -10 and +65 ⁰ C, preferably 0 to 55 ° C holds.

After the addition of alkali hypochlorite is complete, the reaction mass is 0 to 60 minutes, preferably 5 to 15 minutes, held at the reaction temperature.

After the temperature holding period, that containing the alkali salt of 3,6-dialkyl-5-chloruracil becomes Reaction mass for the formation of the free 3,6-Disubstit.-5-chloruratils reacted with a mineral acid such as sulfuric acid.

By adding acid, the above * Schüssige alkali hydroxide neutralized in the reaction mass, then the chloruracil from its alkali salt released so that the acid can be added in two stages.

If a coarse product is required, after the first stage of the acid addition, So after neutralization, seed crystals from a previous batch are added. This vaccination supports the formation of large crystals, which are easier to remove than the finer ones that would occur without inoculation Handle crystals in slurry form and also more easily separate them by filtering or centrifuging leave.

The added used in the first stage acid wini to the reaction mass in the course of such a period that the reaction temperature at 40 to 100 ⁰ C ₁ is maintained preferably 40 to 7 ^{1 0} ^ C. ₁ In general, the additional time is 15 to 30 minutes. The actual duration depends on the rate of heat exchange at the desired temperature. The addition of acid is ended at a pH value at which there is no change in the pH value when the seed crystals are added; this pH value varies with the Uraci produced in each case! and with its concentration.

In the preferred preparation of 3-tert-butyl-5-chloro-6-methyluracil and at a concentration in the reaction mass after chlorination of 7.8%, the pH at the end of the first stage is the addition of acid about 11. Will be at this pH Added seed crystals, they show neither dissolution nor precipitation of further uracil from the Reaction mass.

The seed crystals are added as a slurry and obtained from the previous approach. The amount of seed crystals should be about 2 to 10% correspond to the amount of uracil in the reaction mass.

After the vaccination has ended, the addition of acids is resumed.

To obtain large crystals, the acid is added at a constant rate with good agitation over a period of 30 to 120 minutes. The temperature is maintained by external cooling to 40 to 7O ⁰ C. Some Chloruracilverbindungen subject at temperatures of 8O ⁰ C and above a crystalline transition. In order to achieve the crystal form which is stable at ambient temperature, the temperature should preferably be kept below the crystal transition temperature during the precipitation.

The addition of acid is stopped when the pH of the reaction mass is between 5 and 8, preferably 6.5 and 7.5.

After complete addition of acid, the solid reaction product is obtained, which is on all purposes ^tc prechenden ways, such as filtration or spin feasible. The separated in this way a solid product is then washed with water or slurried in water, wherein the water used for washing or slurrying preferably a temperature of 30 to 8O ⁰ C. The resulting residue is then dried in a conventional manner.

According to another procedure, the reaction mass can be mixed with a solvent such as xylene, toluene or benzene after the chlorination has ended and after acidification, resulting in a two-phase system consisting of an organic layer containing essentially all of the product uracil and a aqueous layer. The resulting mixture is then, if necessary under vacuum, distilled at 50 ° C. to 60 ° C. to remove the organic solvent, while a dilute seed crystal suspension is added to obtain the coarse-particle product. The resulting, crystalline product can be isolated and dried as above.

In the following examples, parts are parts by weight, unless otherwise specified.

803 167

example 1

890 parts of a 24.4 ° / _o solution of 3-tert-butyl-5-chloro-6-methyluraciInatrium is added diluted with 780 parts water and 1003 parts of a 10% sodium hypochlorite solution (stoichiometric excess 16 ° / ₀₎ which is done over 5 minutes with good exercise. The starting temperature is 30 ° C; throughout the addition is cooled from the outside, so that the final temperature of the reaction mass is 45 ⁰ C.

After a temperature holding time of 10 minutes, the pH is adjusted to 11 by adding sulfuric acid to the agitated reaction mass, while the temperature is kept at 45 to 55 ° C. by external cooling. The anlallende solution is then seeded with 10 ° / ₀ of the final slurry from a previous batch, followed by: adjusting the pH of the resulting slurry over 45 minutes under good agitation to 7, while maintaining the temperature by external cooling to 45 to 55 ° C is maintained.

After removing 10% of the slurry for the vaccination of the next batch, the product is isolated by filtration and then washed with 1000 parts of water of 35 C ^r, and dried in a vacuum oven at 70 ° Γ, wherein 227 parts of tert.-3-ButyI- 5-chloro-6-methyluracil (/ ₀ to 70.5 ° Methylacttoaceüic of theory based) with a purity (the infrared-Analysc; be obtained from about ⁰ 9T I _0th

Example 2

35.8 parts of a 10 ^ gen sodium hypochlorite solution (stoichiometric excess 10 ° / ₀ ) are mixed with vigorous agitation in the course of 20 minutes to one of 11.5 parts of S-tert-butyl-o-methyluracil, 5.58 parts 50 ° Oiger, aqueous sodium hydroxide solution and 82.9 parts of water are added while the temperature is maintained at 25 to 35 ° C. by external cooling. The pH is adjusted to 6.5 by adding concentrated sulfuric acid to the solution with vigorous agitation, while the temperature is kept below 70 ° C. by external cooling.

The product is filtered, washed with 25 parts of water and dried, whereby 12 parts (87.5 ⁰ Z ₁ , of theory) S-tert-butyl-S-chloro-o-methyluracil with a degree of purity (determined at a melting point / L) Hrarot correlation <"jrve) of about 97 ° / ₀ arise.

If the above procedure is carried out using 32.9 parts of water, the result is an easier one Decrease in yield and purity of the end product.

If the above working method is used with 39, lPartners Sodium hypochlorite solution (stoichiometric excess 20%) carried out, fall 11.3 parts (84% of theory) of S-tert-butyl-S-chloro-o-methyluracil with a Degree of purity of about 99%.

Example 3

As in Example 1, a solution of the sodium salt of 34ert-butyl-6-methyluracil is prepared. 50 parts of the solution are diluted with 41 parts of water and 46.8 parts of a 10% strength sodium hypochlorite solution (stoichiometric excess 8%) are stirred in over the course of 5 minutes, while the temperature is kept at 0 ° C. by external cooling, then heated the solution to 40 ° C. for a further 10 minutes and the pH value to 6.5 with concentrated sulfuric acid, while the temperature is kept ^{at 35 to 40 ° C. by external cooling.}

The product is filtered, washed with 25 parts of water and dried, 13.6 parts (93.6% of the Theory) 3-tert-Butyi-5-chloro-6-methyluricil with a Degree of purity of about 97%.

The above procedure is carried out using an equivalent amount of 10% potassium hypochlorite ίο instead of sodium hypochlorite repeats "here similar results are obtained.

Example 4

A slurry of 175 parts of tert-butyl urea, 168.5 parts of methyl acetoacetate, 304 parts of xylene and 1 part of concentrated sulfuric acid in the manner described in U.S. Patent 3,254,082 to a 249 parts of methyl 3- (3-tert-butylureido) crotonate Reaction mass containing implemented. Man

ao mixed this reaction mass with a solution of 93 parts of sodium methylate in 340 parts of methanol, 366 parts of solvent are then distilled off and 535 parts of water are added to the residue.

The aqueous layer is separated and washed with a

diluted as the same weight of water. One adds 1143 parts of a 10% sodium hypochlorite solution over the course of 5 minutes with good agitation (stoichiometric excess 32%) added, the temperature during the addition from 28 to 50 ° C increases, and after a further 15 minutes adjusts the pH by adding concentrated sulfuric acid to 6.2 a.

The product is filtered off with 1000 parts of water washed at 35 ° C and dried in a vacuum oven at 70 ° C, with 215 parts (66.7% of theory, based on methyl acetoacetate) i-tert-butyl-S-chloro-6-methyluracil with a degree of purity of over 98%.

Claims (1)

Claim: Process for the preparation of 5-chloro-3,6-dialkyluracils of the general formula R ₁ -N
O Lr ₂ wherein R is an alkyl radical with 1 to IOC atoms and R, denotes an alkyl radical having 1 to 3 carbon atoms, characterized in that an aqueous solution of the sodium or potassium salt of a?, 6-dialkyluracil of the general formula R ₁ -NO R ₂ where R ₁ and R _{1 have} the aforementioned meaning and M ^{f is} a sodium or potassium ion, is reacted with an aqueous solution of sodium or potassium hypochlorite in a 0 to 40% stochmmetric excess at a temperature between -10 and + 65 ° C .