LU84320A1 - PROCESS FOR THE PREPARATION OF PHENMEDIPHAM HERBICIDE - Google Patents

Description

The present invention relates to a process for the preparation of a herbicidal compound, known as phenmedipham.

Phenmedipham is the product of formula 5

CH3 - 0 - CON'rl - | ^ d-0 - CO - NH CHJ

It has already been proposed (French patent 1475241) to prepare this product by reaction of N- (hydroxyphenyl) urethane 10 with an isocyanate or with a chloride of carbamic acid. In this case, the reactions envisaged would therefore be ch3- o - co - nh oh + 0 = C = N CH3 15 or CH, -Q - CO - NH - / S- OH + Cl - CONHr ^ VCH, - * ( I) 3 MT Shoot 3

These methods obviously present difficulties insofar as the reagents each require a particular preparation, in particular the methyl chloroformate used to make methyl metahydroxyphenylcarbamate is an inexpensive reagent. x - An improved method of phenmedipham has therefore been proposed (Chem. Abs. 78 147614 x = Hungarian patent application No. 50-1018 = Hungarian patent 164323) which consists in reacting metaaminophenol with a methanolic solution of phosgene in the presence of an acid fixative such as MgO then, in a second step to react the hydro-xycarbanilate (or hydroxyphenylcarbamate) with phosgene in the presence of dimethylaniline and sodium carbonate, then in a third step we react the carbomethoxyaminophenyl chloroformic acid ester formed with metatoluidine. But this process has various drawbacks in ns nm ?, for the first step, it results in a significant consumption of the base (MgO), whose role is i * 2 to neutralize the HCl which forms and to prevent the formation of aminophenol hydrochloride; and for the rest of the process, there is on the one hand the need to neutralize the HCl which forms using a base and on the other hand the coexistence of HCl and water makes the medium corrosive which is very troublesome industrially.

One could think of solving the problems of the first stage by using techniques as described in US Pat. Nos. 3,933,470 and French 1,559,479 which consist in preparing metahydroxyphenoxycarbamate by heating aminophenol with phosgene, then methanol, but it is Difficult to avoid the reaction of the isocyanate formed either with the aminophenol or else on itself, so that oligomers are formed which lead to a phenmedipham of insufficient purity.

It is therefore clear that there is a need to find a simple and economical process for the preparation of phenmedipham and that, despite many possibilities, such a process has not yet been found. Additionally, this process should provide high purity phenmedipham.

An object of the invention is to provide such a method.

The process of the invention is characterized in that metaaminophenol is reacted with phosgene at low temperature in a solvent of alkyl alkanoate type, then methanol is reacted with the reaction solution thus obtained then, again in the same solution, metatolyl isocyanate is reacted in the presence of an organic base.

During the first reaction stage, the compound of formula * HO ^^ jNH - CO - Cl is also formed, known as metahydroxyphenylcarbamic acid chloride.

35 After reaction with methariüj. this ûiuùiuicî u * acxoe is transformed into methyl metahydroxyphenylcarbamate, which c> · 3 with metatolyl isocyanate gives phenmedipham.

As alkyl alkanoate, it is preferred to use methyl alkanoates and more particularly acetate or propionate.

To practically carry out the reaction of phosgene with metaaminophenol, it is preferable to add (with stirring) metaaminophenol to a solution of phosgene in the solvent alkanoate.

The reaction temperature is generally between -20 and + 40 ° C, preferably between 10 and 30 ° C.

Metaaminophenol is added as a solution in the solvent alkanoate; to have concentrated solutions, hot solutions can be used.

The phosgene concentration varies during the reaction but the initial concentration is generally between 10 and 60% by weight; at the end of the reaction, this concentration can become very low, or even zero.

The amount of reagents used is such that their phosgene_ molar ratio is between metaaminophenol 1 and 2, preferably between 1.05 and 1.4.

*

During the reaction, insoluble metaaminophenol hydrochloride is formed at least partially, but by continuing the reaction with stirring in the temperature zone already indicated, this hydrochloride itself reacts to give the acid chloride normally. metahydroxyphenylcarbamic in solution in the alkanoate.

When phosgene remains in the reaction medium at the end of the reaction, it is preferable to remove it, for example by evaporation or distillation or entrainment; this elimination takes place at a temperature generally between 10 and 40 ° C.

The next reaction with methanol is conveniently carried out by adding methanol to the solution obtained above. The quantity of methanol used is generally such that the molar ratio _ methanol used is between 1 metaaminophenol initially charged and 10 preferably between 3 and 8.

The reaction is generally carried out between 20 and 100 ° C (under pressure when it is above the boiling temperature of the mixture).

A solution of methyl metahydroxyphenyl carbamate is thus obtained; certain volatile compounds are then removed, for example by distillation. As compounds which can be eliminated, mention may be made of hydrochloric acid and excess methanol as well as, optionally, part of the solvent alkanoate.

To carry out the third and last step of the invention, metatolyl isocyanate and an organic base are added to the solution obtained previously of methyl metahydroxyphenylcarbamate in the alkanoate. Other products may possibly be present as will be explained below.

The amount of metatolyl isocyanate added is advantageously such that its molar ratio with the meta-aminophenol used in the first stage is between 1 and 1.5, preferably between 1.02 and 1.2.

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The reaction is most often carried out between 20 and 120 ° C (under pressure if necessary), preferably between 40 and 80 ° C.

As organic base, tertiary amines such as trialkylamines, in particular triethylamine, are preferred. The amount of base used is between 0.1 and 10%, this percentage being counted by mole relative to the metatolyl isocyanate "used.

At the end of the reaction, the phenmedipham formed is conveniently separated by simple cooling of the reaction mixture. This yes leads to the crystallization of a phenmerlinham of excellent purity.

5

The mother crystallization solution containing, in addition to the alkanoate solvent, phenmedipham, excess metatolyl isocyanate as well as the organic base can be reused for a new operation for carrying out the third step of the process of the invention .

In this case, three solutions are thus mixed: this recycled mother solution, the methyl metahydroxy-phenylcarbamate solution obtained during the second step, a metatolyl isocyanate solution. A particular addition of organic base is then not useful. The third step of the process of the invention is then carried out as already indicated. It may be necessary to distill part of the solvent to crystallize phenmedipham.

The yields of the various reaction steps of the invention are practically quantitative.

An advantage of the process of the invention is to provide high purity phenmedipham due to the high purity of the methyl metahydroxyphenylcarbamate produced intermediately according to the invention.

The following example, given without limitation, illustrates the invention and shows how it can be put into practice.

EXAMPLE 25 13.95 g of methyl acetate are charged into a 0.5 l flask provided with stirring and an inert atmosphere.

Cooled to -20 ° C and then introduced into the flask gaseous phosgene which liquefies at this temperature; the addition of phosgene is continued until 14.01 g have been added.

Then gradually added over 7 min a solution brought to 50 ° C of 11.9 g of metaaminophenol in 120 cm3 of methyl acetate while maintaining the temperature 55 of the reaction medium between 6 and 6 ° using a cooling bath.

6

The temperature is allowed to return to 26 ° C and then stirred 45 min at this temperature; the reaction medium is then clear and colorless.

The excess phosgene is evaporated by distillation under vacuum at 30 ° C.

To the solution of carbamyl chloride in methyl acetate thus obtained is added 22 cm of methanol and the whole is brought to the boil at reflux for approximately 1 h 30 min (temperature: approximately 50 ° C.).

Various volatile fractions are eliminated (ternary mixture HCl, CH ^ OH, CH ^ COOCH ^; azeotrope CHjOHCH ^ COOCH ^> CH ^ COOCH ^) by distillation which is stopped when the reaction mixture reaches 80 ° C.

To the reaction mass thus obtained, 0.11117 g of triethylamine and 16.8 g of metatolytic isocyanate are added, which gives rise to the formation of an abundant precipitate. 100 cm ^ of methyl acetate are added and the mixture is boiled for 1 hour (temperature in the region of 60 ° C.). The reaction medium is then homogeneous. Allow to cool to room temperature. Phenmedipham precipitates. Filter, * concentrate the filtrate, filter again. By recovering all of the phenmedipham, 29.3 g of product are obtained, ie a yield of 89.6%.

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Claims (8)

1. Process for the preparation of phenmedipham, characterized in that metaaminophenol is reacted with phosgene at low temperature in an alkyl alkanoate as solvent so as to make the chloride of meta-droxyphenylcarbamic acid, then that methanol is reacted with the reaction solution thus obtained and then reacted on this solution with metatolyl isocyanate in the presence of an organic base. 2. Method according to claim 1) characterized in that the alkanoate is acetate or propionate. 15 3) Method according to one of claims 1 or 2) character ized in that the reaction temperature between phosgene and metaaminophenol is between -20 and + 40 ° C and / or that the reaction temperature between methanol and the reaction medium is between 20 and 100 ° C. and / or that the reaction temperature between metatolyl isocyanate and methyl metahydroxyphenylcar- $ - bamate is between 20 and 120 ° C. „4) Process according to claim 3) characterized in that the reaction temperature between phosgene and meta-aminophenol is between 10 and 30 ° C and / or that the reaction temperature between metatolyl isocyanate and methyl metahydroxyphenylcarbamate is between 40 and 80 ° C. 5. Method according to one of claims 1 to 4) characterized in that the molar ratio with the meta aminophenol used is between 1 and 2 for phosgene, and / or between 1 and 10 for methanol and / or between 1 and 1.5 for metatolyl isocyanate. 6. Method according to claim 5) characterized in that * 2 C 1 a <ηΛηπηπ4 · λλΤ λ ί λ 1 λ r "^" "** '" .λ · ". U ^> ^ ^ Φ awa μ ^ ν i11 uu ▲ X Ο ("IV ^ V_r JL U 111 U la Cl Cl III .LIIU | J 1 ICIIU JL COW ^ U III JJ X JL d between 1.05 and 1, 4 for phosgene, and / or between 3 and 8 * * * 8 T for methanol and / or between 1.02 and 1.2 for metatolyl isocyanate. 7. Method according to one of claims 1 to 7) characterized in that the organic base is a trialkylamine, preferably triethylamine. 8. Method according to one of claims 1 to · 7) characterized in that the phenmedipham is separated by cooling-ment and that the remaining solution is recycled in the reaction medium between metatolyl isocyanate and 10 methyl metahydroxyphenylcarbamate . »JL i ♦ *