DE2827977A1 - Prodn. of mandelic acid esters - by alcoholysis of mandelonitrile cpds. used as herbicide intermediates - Google Patents

Abstract

Prodn. of esters of formula (I) comprises subjecting the coresp. nitriles of formula (II) to alcoholysis with an alcohol of formula (III): (R is alkyl; X is alkyl, aryl, OH, alkoxy, alogen, haloalkyl and/or NO2; n = 0-3). Alcoholysis is effected by reacting 1 mole of (II) with 3-20 (pref. 5-16) moles of (III) at 40-160 degrees C (pref. 45-100 degrees C) for 3-10 hr. in the presence of 1.8-3 (pref. 2.1-2.5) moles of HCl or =u mole of H2O and 1.2-2.j (pref. 1.3-2.2) moles of HCl. Then either (a) the reaction mixt. is worked up and the product isolated in conventional manner; or (b) NH4Cl is recovered in solid form by neutralising excess HCl with gaseous NH3, adding an opt. chlorinated aromatic hydrocarbon (IV), distilling off excess alcohol, cooling, filtering off crystalline NH4Cl and isolating (I) from the organic filtrate by distn. Cpds. (I) are intermediates, e.g. for herbicides.

Description

Process for the production of mandelic acid esters

The present invention relates to a one-step method of manufacture of mandelic acid esters, starting from mandelic acid nitriles (benzaldehyde cyanohydrins), at the same time the nitrile nitrogen is obtained in the form of solid ammonium chloride will. Mandelic acid esters can be used as intermediate products, e.g. for the production of herbicidal Active ingredients.

The syntheses of mandelic acid esters known from the literature The nitriles are usually carried out in two stages via the imino ether hydrochloride and deliver yields of approx. 73% (cf. Chem. Abstr. Vol.

70, 11 290r (1969); see also Houben-Weyl, methods of organic Chemie, 4th Edition, Volume VIII, p. 539).

A single-stage conversion of mandelonitrile is also already in the literature has been described for ethyl mandelate; however, this was only a yield of approx. 50% achieved (J. Prakt. Chem. (2) Vol. 150, p. 90 (1938)).

There is also a particular disadvantage of these previously known methods in that the nitrogen present in the nitrile group is not utilized, but is lost in the work-up or only with extraordinary effort in form can be isolated from ammonium salts.

It has now been found that mandelic acid esters of the formula in which R stands for alkyl, X stands for alkyl, aryl, hydroxy, alkoxy, halogen, haloalkyl and / or nitro and n stands for an integer from 0 to 3, by reaction of mandelic acid nitriles (benzaldehyde cyanohydrins), alcohols and hydrogen chloride to a high degree high yield and with very good purity and at the same time the nitrile nitrogen is obtained in the form of solid ammonium chloride if mandelic acid nitriles of the formula in which X and n have the meaning given above, per mol with 3 to 20 mol of an alcohol of the formula R-OH (III) in which R has the meaning given above, and either with 1.8 to 3 mol of hydrogen chloride or with addition of up to 1 mole of water with 1.2 to 2.4 moles of hydrogen chloride at temperatures between 40 and 160 ° C. and, after a reaction time of about 3 to 10 hours, excess hydrogen chloride is neutralized with gaseous ammonia, an aromatic, optionally chlorinated hydrocarbon is added and for Working up, the excess alcohol is distilled off, after cooling the precipitated crystalline ammonium chloride is filtered off and the mandelic acid ester is isolated from the organic filtrate by distillation.

In view of the state of the art, it is extremely surprising to indicate that it is possible under the conditions of the process according to the invention Mandelonitriles in a technically simple manner with high yield in very pure To lead to over flandelic acid, at the same time solid ammonium chloride lets win.

The method according to the invention has a number of advantages. In particular, the new, one-step process gives yields of mandelic acid esters (over 90% of theory), which goes far beyond the comparable known processes achievable yields (50 to 70%) go beyond. The new procedure stands out compared to the previously known production methods essentially from the fact that a Excess of hydrogen chloride per ol of mandelonitrile (II) at elevated temperature is used in the presence of excess alcohol (III). Through this measures the otherwise occurring, yield-reducing side reactions can largely be eliminated suppress. As a result, the proportion of by-products is minimal, and that through Mandelic acid esters isolated by vacuum distillation can be used immediately without further purification can be used for subsequent implementation. An added benefit of the new Process consists in that it succeeds in a technically simple manner, the nitrogen the nitrile group directly in the form of solid, crystalline ammonium chloride. In contrast, the previously known processes of this type always resulted in an aqueous one Salt solution, from which the ammonium chloride is only through technically complex and energy-consuming Operations could be won; since you usually have to do without this, it works Up to now, ammonium chloride has practically always been lost of alcohol and hydrogen chloride to form alkyl chlorides, which easy to isolate from the reaction mixture due to their relatively low boiling points are.

If mandelonitrile (benzaldehyde cyanohydrin), ethyl alcohol and hydrogen chloride are used as starting materials, the course of the reaction can essentially be represented by the following (stoichiometric) equation, although the excess of ethyl alcohol and hydrogen chloride required according to the invention is not taken into account: + 2 C2H5 ° ~ + CH-CN 2 HCl HC HCl OCH CN + 2 C2H5OH oNH OC2H5 OH - C2H5Cl (not isolated) (-H20) + H2O O H-COOC2H5 + NH4Cl Ar-H OH (solid, crystalline) "Ar-H" denotes an aromatic, optionally chlorinated, hydrocarbon.

The mandelonitriles (benzaldehyde cyanohydrins) to be used as starting materials are generally defined by the formula (II). The index is in this formula n preferably represents 0 and 1. The radical X preferably represents alkyl with 1 to 4 C atoms, phenyl, hydroxy, alkoxy with 1 to 2 C atoms, chlorine, halomethyl, in particular Trifluoromethyl as well as for the nitro group. Examples include: benzaldehyde cyanohydrin, 4-methylbenzaldehyde cyanohydrin, 3-ethylbenzaldehyde cyanohydrin, 4-tert-butylbenzaldehyde cyanohydrin, 4-phenylbenzaldehyde cyanohydrin, 3-hydroxy and 4-hydroxybenzaldehyde cyanohydrin, Anisaldehyde cyanohydrin, 3-chlorobenzaldehyde cyanohydrin, 4-trifluoromethylbenzaldehyde cyanohydrin, 3-nitro- and 4-nitrobenzaldehyde cyanohydrin.

The mandelonitriles (II) to be used according to the invention are largely known and can in a known manner by reacting the corresponding benzaldehydes can be produced with hydrocyanic acid (see e.g. Houben-Weyl, Methods of Organ. Chemistry, 4th edition, Volume VIII, p. 274 ff.) The continue from starting materials Alcohols to be used are generally defined by the formula (III). It says R preferably for alkyl having 1 to 6 carbon atoms. Examples include: methanol, Ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-hexanol.

The alcohols (III) used in each case also serve at the same time as a diluent.

The inventive method is in the temperature range from 40 to 1600C, preferably from 45 to 100 ° C. When making the methyl and Ethyl ester is most appropriately chosen as the reaction temperature, the boiling point of methyl or ethyl alcohol.

When carrying out the process according to the invention, one sets up 1 mol of mandelonitrile of the formula (II) has an excess of 3 to 20 mol, preferably from 5 to 16 moles, alcohol (III). If you work without the addition of water, then sets one mole of mandelonitrile (11) further 1.8 to 3 mol, preferably 2.1 to 2.5 moles, hydrogen chloride.

If you work with the addition of water, 1 mole of mandelonitrile is used (II) up to 1 mole, preferably 0.4 to 0.8 moles, of water and 1.2 to 2.4 moles, preferably 1.3 to 2.2 moles of hydrogen chloride. (This addition of water causes a part of the water required for ester formation is not caused by the reaction between alcohol and hydrogen chloride must be formed; you can therefore use the excess of hydrogen chloride decrease, then, however, gains correspondingly less alkyl chloride3 Reaction times are generally about 3 to 10 hours.

After the reaction has ended, excess hydrogen chloride is still free neutralized with gaseous ammonia, expediently up to a pH value between 3 and 4, preferably between 3.3 and 3.9. The reaction mixture then becomes an aromatic one optionally chlorinated hydrocarbon added to the ammonium chloride formed to be deposited completely in solid form. The hydrocarbon or chlorinated hydrocarbon can be added as a liquid or more advantageously as a vapor, so that at the same time part of the amount of heat required to evaporate the excess alcohol is fed.

For 1 part by weight of mandelonitrile there is generally 1 to 20 Parts by weight, preferably 2 to 15 parts by weight, of the aromatic hydrocarbon or chlorinated hydrocarbons are used.

As aromatic hydrocarbons or chlorinated hydrocarbons are such compounds are suitable whose boiling points are higher than that of the alcohol used such as benzene, toluene, cumene, xylene, chlorobenzene, dichlorobenzene, chlorotoluene.

Simultaneously or after the addition of the aromatic hydrocarbon or chlorinated hydrocarbons to the reaction mixture, heat is added to the system, to distill off the alcohol. This process can take place at elevated pressure, normal pressure or negative pressure can be carried out.

The entire process can be carried out in continuous approaches or in be carried out continuously. When the reaction is carried out continuously it is special It is recommended to put the reaction mixture in a distillation column feed and against this product stream the vapor of the aromatic hydrocarbon to let flow.

The alcohol should be separated off from the reaction mixture to the extent that that the content of this compound in the mixture is below 0.3%.

The ammonium chloride is formed when this process is carried out in crystalline solid form. The size of these crystals depends largely on the The rate at which the alcohol is removed from the reaction mixture. The faster this happens, the smaller the ammonium chloride crystals that are formed.

It is therefore advantageous to use most of the alcohol during a To be separated by distillation over a period of about 0.5-5 hours. The elimination the remaining quantities can then be made quickly without the mean grain size being decisive is reduced.

The solid ammonium chloride can be removed by filtration or centrifugation can simply be separated from the solution of the mandelic acid ester. It will be with the aromatic hydrocarbon or chlorinated hydrocarbon and then washed dried. The washing liquid is fed back into the process.

The mandelic acid esters formed are obtained from the filtrate in the usual way Way isolated by distillation.

Most of the mandelic acid esters of the formula (I) which can be prepared according to the invention are known; they can be used, for example, as intermediates for the production of pharmaceuticals and pesticides, in particular herbicides. For example, the herbicidally active compound 4-amino-3-methyl-6-phenyl-1,2,4-triazin-5 (4H) -one is obtained from the methyl mandelate (1) according to the following reaction scheme (cf. DE-OS 2 224 161): 1st stage 2nd stage is not isolated 3rd stage 1st stage 0.7 mol of methyl mandelate (1) are dissolved in 200 g of glacial acetic acid. This solution is added dropwise to a mixture of 700 g of glacial acetic acid and 0.9 mol of chromium trioxide (CrO3) 0 within 30 minutes at 50.degree. After stirring for 2 hours at this temperature, most of the acetic acid is distilled off in vacuo at 20 mbar.

The distillation residue is mixed with 1126 g of water. The organic The phase is separated off and the aqueous phase is treated 3 times with 100 g of methyl isobutyl ketone each time extracted. The combined organic phases are fractionated in vacuo. Of the Main run (102.5 g) boils at 16 mbar between 120 and 1260C. The yield of methyl phenylglyoxylate (A) is 89.5% of theory

2nd stage 1 mol of phenylglyoxylic acid methyl ester (A) and 1 mol of acetylhydrazine are refluxed in 780 g of isopronol for 5 hours. As a catalyst added some p-toluenesulfonic acid. The hydrazone (B) precipitates as a mixture of isomers an isomer crystallizes. Therefore will continued working without isolating the hydrazone. After the ester is added to this reaction solution is consumed, given hydrazine hydrate and kept at 20 ° C. for 5 hours with stirring. The reaction mixture is then cooled to 0 ° to 50 ° C. and filtered off with suction. The yield of pure hydrazide (C) is 85%.

3rd stage 1 mol of hydrazide (C) is mixed with 1000 g of isopropanol and Stirred for 24 hours at 1000C in a closed vessel (1-2 bar overpressure). Afterward is sucked off at 0 -5 ° C. 4-Amino-3-methyl-6-phenyl-1 is obtained in 84% yield , 2,4-triazin-5 (4H) -one (D) of melting point 167-1690C.

The process according to the invention is illustrated by the preparation examples below. Preparation examples g P example 6 mol of methanol were placed in a 3-necked flask equipped with a stirrer, reflux condenser and dropping funnel and heated to 50.degree. Then 1 mol of benzaldehyde cyanohydrin and a solution of 2.5 mol of hydrogen chloride in 4 mol of methanol were added dropwise as quickly as possible.

The reaction mixture was then under 6.5 hours at 65 0C Heated to reflux. During this time, 0.95 mol of methyl chloride escaped through the cooler (CH3Cl), which can be condensed in a cold trap.

Then the reaction mixture with gaseous NH3 on a The pH was adjusted to 3.5 and 700 g of toluene were added. Then it was at normal pressure a mixture of methanol and toluene is distilled off. After within 3 hours 500 g of distillate were obtained, a further 500 g of toluene were added to the batch. The distillation was then continued until a GC analysis of the contents of the flask resulted in a content of 0.1% methanol.

The reaction mixture was finally cooled and filtered. Of the The filter residue was washed with 100 g of toluene and then dried; he passed from 72 g of solid ammonium chloride The filtrate and the one for washing Amount of toluene used of the ammonium chloride were combined and distilled worked up.

154 g of methyl mandelate are obtained (yield 93.6% of theory); Boiling point 123.5 - 1240C at 13.4 mbar.

Example 2 Under the conditions of Example 1, 5 mol of benzaldehyde cyanohydrin, 55 moles of methanol and 11 moles of hydrogen chloride reacted. Escaped during the reaction 4.8 moles of methyl chloride. The reaction mixture was neutralized with gaseous 2 kg of chlorobenzene are added to NH3 (pH = 3.85). Over the course of 5 hours, Normal pressure, the methanol is distilled off until the temperature of the distilling vapors had reached the boiling point of chlorobenzene.

The reaction mixture was cooled and filtered. The residue was washed with 500 g of chlorobenzene and then dried. There were 307 g of solid ammonium chloride obtained, the mean grain size of which was 0.15 mm.

The filtrate and the amount of chlorobenzene used to wash the ammonium chloride were combined and worked up by distillation.

786 g of methyl mandelate were obtained, yield 95% of theory); Boiling point 123.5 - 1240C at 13.4 mbar.

Example 3 In a mixture of 1 mol of benzaldehyde cyanohydrin, 0.5 mol Water and 16 mol of methanol became 1.3 mol of HCl gas in the course of 45 minutes at about 500C initiated. The reaction mixture was then refluxed for a further -9 hours cooked. In the process, 0.21 mol of methyl chloride escaped through the cooler in a cold trap were condensed.

The reaction mixture was then passed in gaseous NH3 neutralized (pH = 3.6) and mixed with 6.6 mol of chlorobenzene. Then it was distilled until the bottom of the reaction no longer contained any methanol. Cool to room temperature and filtered off the precipitated ammonium chloride and washed it with chlorobenzene. After drying, 61 g of solid ammonium chloride were obtained.

Analytically, 0.07 mol of methyl chloride was still present in the methanolic distillate to prove. The filtrate and the amount of chlorobenzene used to wash the ammonium chloride were combined and again worked up by distillation.

150 g of methyl mandelate (1) were obtained (yield 91% of theory); Boiling point 123.5 to 1240C at 13.4 mbar.

Claims (8)

Claims 1. Process for the preparation of mandelic acid esters of the formula in which R stands for alkyl, X stands for alkyl, aryl, hydroxy, alkoxy, halogen, haloalkyl and / or nitro and n stands for an integer from 0 to 3, by reaction of mandelonitriles with alcohols and hydrogen chloride, in which at the same time the Nitrile nitrogen is obtained in the form of solid ammonium chloride, characterized in that mandelic acid nitriles of the formula in which X and n have the meaning given above, per mol with 3 to 20 mol of an alcohol of the formula R-OH (III) in which R has the meaning given above, and either with 1.8 to 3 mol of hydrogen chloride or with addition Reacts of up to 1 mol of water with 1.2 to 2.4 mol of hydrogen chloride at temperatures between 40 and 1600C. and after a reaction time of about 3 to 10 hours, excess hydrogen chloride is neutralized with gaseous ammonia, an aromatic, optionally chlorinated hydrocarbon is added and the excess alcohol is distilled off for work-up, the precipitated crystalline ammonium chloride is filtered off after cooling and the mandelic acid ester is isolated from the organic filtrate by distillation . 2. The method according to claim 1, characterized in that at Temperatures between 45 and 1000C will work. 3. The method according to claim 1, characterized in that one pro Mol of mandelonitrile of the formula (II) 5 to 16 mol of an alcohol of the formula (III) begins. 4. The method according to claim 1, characterized in that one pro Mol of mandelonitrile (II) uses 2.1 to 2.5 mol of hydrogen chloride. 5. The method according to claim 1, characterized in that one pro Moles of mandelonitrile (II) up to 1 mole of water and 1.3 to 2.2 moles of hydrogen chloride begins. 6. The method according to claim 1, characterized in that as Starting material of the formula (II) mandelonitrile and as an alcohol of the formula (III) Methanol or ethanol is used. 7. The method according to claim 1, characterized in that as aromatic, optionally chlorinated hydrocarbons benzene, toluene, cumene, Xylene, chlorobenzene, dichlorobenzene or chlorotoluene is used. 8. The method according to claim 1, characterized in that one is on 1 part by weight of mandelonitrile 1 to 20 parts by weight, preferably 2 to 15 parts by weight of the aromatic, optionally chlorinated hydrocarbon is used. 9-. Process according to claim 1, characterized in that gaseous Ammonia up to a pH value between 3 and 4, preferably between 3.3 and 3.9, inflicts.