IE68772B1 - Process for the synthesis of acyl cyanides - Google Patents

Abstract

Process for the synthesis of acyl cyanides of formula: <IMAGE> in which R denotes an alkyl, cycloalkyl or aryl radical or a heterocyclic residue, consisting in reacting acyl halides of formula: <IMAGE> in which R has the above definition and X denotes a halogen, with alkali metal cyanides, characterised in that the reaction takes place in the presence of a product containing alkylene oxide units and in the presence of catalytic quantities of water.

Description

The present invention relates to a process for the synthesis of acyl cyanides. This process consists in i reacting acid halides with an alkali metal cyanide. Acyl cyanides are intermediates for the organic synthesis of, for example, herbicides.

FR Patent 2,353,524 describes a synthesis of benzoyl cyanide CgH5COCN by reaction of benzoyl chloride with sodium cyanide in molar excess in the presence of nitrile acid and of copper cyanide. FR Patent 2,346,323 describes a similar but much more general reaction, since the latter applies to a whole group of acyl cyanides and consists in reacting sodium cyanide with an acid halide in excess in the presence of copper or zinc cyanide.

These processes have the disadvantage of requiring the presence of heavy metals and therefore impose complicated treatments to avoid their presence in the effluents. In Tetrahedron Letters (Pergamon Press) No. 26, pages 22752278 (1974) there is disclosed a process limited to the synthesis of benzoyl cyanide by reaction of sodium cyanide with benzoyl chloride in solution in methylene chloride and in the presence of tetrabutylammonium bromide; the C6H5COCN yield on CgH5COCl does not exceed * 60 %. FR Patent 2,364,894 describes the synthesis of C6H5COCN by reaction of C6H5COC1 with NaCN in a solvent in the presence of benzoic anhydride (CgH5CO-O-CO-CgH5) or of products which can generate benzoic anhydride under the reaction conditions. Example 1 of this patent was e reproduced, that is to say the reaction of benzoyl chloride, benzoic anhydride and sodium cyanide in xylene ϊ between 140 and 145°C for 8 hours, and a 51.2 % molar yield of benzoyl cyanide on the combined benzoic anhydride and benzoyl chloride used was found, and a degree of conversion of 60.5 % of the benzoyl chloride used. This was repeated, this time employing moist sodium cyanide (0.4 g of water per 36.75 g of NaCN); the yield rose from 51.2 to 88.2 %.

Example 2 was also reproduced, that is to say the reaction of benzoyl chloride, sodium cyanide and sodium benzoate in xylene at 135°C. The benzoate is presented as having to generate benzoic anhydride by reaction with benzoyl chloride. A degree of conversion of 23 % of the benzoyl chloride used was found and a 14.9 % molar yield of benzoyl cyanide relative to the benzoyl chloride used, instead of 94 % as announced. This Example 2 was repeated, but this time employing moist sodium cyanide (0.5 g of water per 29.4 g of NaCN); the degree of conversion changed from 23 to 85.7 % and the yield from 14.9 to 67.8 %.

The presence of water is therefore necessary to * obtain an economically acceptable yield according to FR 2,364,894.

Example 3 of FR 2,364,894 concerns the reaction of benzoyl chloride, sodium cyanide and water in xylene at 135°C. This is similar to Example 2, but the benzoate as anhydride precursor is replaced with water. This Example 3 was reproduced and, after 2 hours' heating to 135°C, the yield did not exceed 60 %.

A new process has now been found, according to the present invention, for preparing acyl cyanides, which gives better yields at lower temperature, and this greatly reduces the reaction byproducts and is reproducible. The present invention provides a process for the synthesis of acyl cyanide of formula (I): O II R-C-CN (I) in which R is either an alkyl radical containing from 1 to 8 carbon atoms or a cycloalkyl radical containing from 3 to 12 carbon atoms, or an aryl radical, or a heterocyclic residue which may be condensed with a benzene nucleus, all these radicals R being optionally substituted, which comprises reacting acid halides of formula (II): O II R-C-X (II) in which R has the above definition and X denotes a halogen, with alkali metal cyanides, characterized in that the reaction takes place in the presence of a product containing alkylene oxide units and in the presence of catalytic quantities of water.

* The reaction of the invention takes place according to the formula: 0.0 « II II R-C-CX + MCN---> R-C-CN + MX in which M denotes an alkali metal and is advantageously performed in a solvent. After the reaction the alkali metal halide and the optional excess of alkali metal cyanide can be removed by filtration and washed with solvent. The pure acyl cyanide can be obtained by distillation of the filtered reaction mixture.

The acid halides employed as starting materials are defined by the formula (II). In this formula R preferably denotes a linear or branched alkyl radical containing from 1 to 4 carbons which can be substituted; R also preferably denotes a cycloalkyl radical containing 5 or 6 carbons which can be substituted; R also preferably denotes a phenyl or naphthyl radical which can be substituted; R also preferably denotes a 5 or 6 membered heterocyclic residue, substituted if appropriate.

In formula (II), X advantageously denotes chlorine or bromine.

The acid halide employed is generally added a * little at a time to the reaction mixture with stirring, t in pure form or diluted with the reaction solvent. The addition period may vary from, say, a few minutes to several hours.

The preferred period is approximately 1 hour.

The alkali metal, preferably sodium or potassium, cyanide is employed in stoichiometric quantity or else in 5 excess, typically in a proportion of 1 to 2 moles per mole of acid halide; the preferred quantity is from 1 to 1.25 moles per mole of acid halide.

The reaction takes place advantageously in the presence of an inert solvent.

Any solvents which do not react with the acid halide or with the alkali metal cyanide under the reaction conditions can be employed.

As a solvent which is suitable for the reaction there may be mentioned: - benzene-related hydrocarbons such as benzene, toluene, xylene or chlorobenzene, - halogenated aliphatic hydrocarbons such as trichloroethylene or tetrachloroethane, - ethers or esters which are inert under the reaction conditions.

The preferred solvents for the reaction are toluene and xylene.

* The quantity of solvent may vary within wide limits. From 150 to 500 ml per mole of acid halide is advantageously used. A larger quantity of solvent can be employed, but it would be necessary to distil a larger quantity to recover the acyl cyanide. ‘ c.

The reaction is typically performed at a temperature of 60 to 150°C, the preferred temperature 4 being 90 to 120°C.

The reaction is advantageously performed at atmospheric pressure if the solvent which is chosen allows it. The reaction can also be performed under inert gas pressure, or under solvent vapour pressure when the boiling point of the chosen solvent is lower than the reaction temperature.

The reaction is very fast and is, for example, finished after 15 to 30 minutes at 120°C. However, heating can be continued for a period of, say, 1 to 2 hours to remove any trace of acid halide. The preferred reaction period is 2 hours at 95°C.

The product containing alkylene oxide units advantageously contains 2 to 200 units chosen from ethylene oxide and propylene oxide.

It is, for example, a product containing one or more chains: O-(CH2-CH2"O)n-CH2-CH2-OH the total number of the n or n's being from 2 to 200; there may also be mentioned: * - polyoxyethylenated alkylphenols: i R * 0 (CH2 _ch2°) n"CH2"CH2OH where R‘ is an alkyl containing up to 20 carbons, R' being, for example, C8H17 or C9H19 or C12H17, n being from 20 to 100; - polyoxyethylenated stearates: ch3-(ch2)16-coo-(CH2-CH2O)n-ch2-ch2-oh - simple polyethylene glycols of formula: OH-(CH2-CH2O)n-CH2-CH2-OH of molecular mass from 100 to 4000.

Among the agents which have a number of polyethylenated chains there may be mentioned the triglyceride derivatives of polyethylene glycols in which the total number of ethylene oxide units is from 20 to 150.

Products which are similar to the above products can be employed, in which the ethylene oxide unit is replaced by the propylene oxide unit or a mixture of ethylene oxide and propylene oxide units.

The quantity of this product is suitably from 0.1 to 10 g per mole of acid halide, the preferred quantity being from 0.4 to 2 g (per mole).

The product is generally added to the reaction solvent, but it can also be added wholly or partly with the pure or solvent-diluted acid halide. Small quantities of water must be added to the reactants to obtain a high yield and degree of conversion.

The quantity of water which must be present during the reaction is generally 0.2 to 2 g of water per mole of acid halide. The preferred quantity of water is C from 0.5 to 1 q of water per mole of acid halide.

The way in which the water is introduced must << ensure a good distribution thereof over the reactants.

In the following Examples, which further illustrate the present invention, the degree of conversion expresses the quantity of acid halide which has disappeared, relative to the initial quantity and the yield expresses the ratio of the number of moles of acyl cyande obtained to the number of moles of acid halide which were initially present.

EXAMPLE 1 36.75 g of anhydrous sodium cyanide (0.75 mol) and 0.4 g of water are added to a glass reactor fitted with a stirrer and a condenser, containing 150 cm3 of xylene and 0.5 g of polyoxyethylenated nonylphenol of formula: CgHj 9-^Q^-O- (CH2-CH2O) 100-CH2-CH2OH (marketed by GAF under the name of Antarox CO 990). 70.3 g of benzoyl chloride (0.50 mol) are then run in over 0.5 hours at 125°C and the temperature is raised to 140ec for 2 hours.

After cooling, the inorganic precipitate (42.9 g) is filtered off and washed. i.

The filtrate is distilled and 60.05 g of pure benzoyl cyanide are collected, that is a 91.6 % yield.

EXAMPLE 2 24.5 g of sodium cyanide (0.5 mol) and 0.5 g of water are added to a glass reactor fitted with a stirrer and a condenser, containing: 150 cm3 of xylene and 0.5 g of Antarox CO 990.

These are heated to 95°C and 70.3 g of benzoyl chloride (0.5 mol) are run in over 1 hour. The temperature is kept at 95°C for two hours and then, after cooling, the solid is filtered off and washed with xylene (29.2 g of inorganic precipitate).

A xylene solution with a mass of 231.4 g is obtained after filtration. Gas chromatography analysis with an internal standard determines 26.3 % of benzoyl cyanide, that is a total quantity of 60.85 g of pure benzoyl cyanide, corresponding to a 92.8 % yield.

EXAMPLE 3 The procedure is as in Example 2, with: 150 cm3 of xylene, 0.5 g of Antarox CO 990, 29.4 g of anhydrous sodium cyanide (0.6 mol), 0.4 g of water, 70.3 g of benzoyl chloride (0.5 mol)e After reaction, a degree of conversion of 99 % of the benzoyl chloride is obtained, and a yield, relative to the benzoyl chloride used, amounting to 86.2 %.

EXAMPLE 4 (not in accordance with the invention) When proceeding exactly as in Example 3, but omitting to add water, a degree of conversion of 32 % and a chemical yield of 23.8 % are obtained.

EXAMPLE 5 (not in accordance with the invention and similar to Example 3 of FR 2,364,894) When proceeding exactly as in Example 3, but omitting to add the polyoxyethylene derivative (Antarox CO 990), a degree of conversion of 79 % and a 70.2 % yield are obtained.

EXAMPLE 6 The procedure is exactly as in Example 3 but Antarox CO 990 is replaced with Antarox CO 850 of formula: A degree of conversion of 99 % and an 81.5 % yield are obtained.

EXAMPLE 7 The procedure is exactly as in Example 3, but with Antarox CO 990 being replaced with a stearate polyethoxylated with 100 ethylene oxide units, marketed by ICI under the name of Brij 700 of formula: CH3-(CH2) 16-COO-(CH2-CH2O) jOO-CI^-CHjOH A degree of conversion of 99 % and an 84.6 % yield are obtained.

EXAMPLE 8 The procedure is exactly as in Example 3, but with Antarox CO 990 being replaced with a triglyceride of polyoxyethylene glycol with 150 ethylene oxide units, marketed by Atlas under the name of G 1295.

The degree of conversion is 98.8 % and the yield is 83.3 %.

EXAMPLE 9 The procedure is exactly as in Example 3, but with Antarox CO 990 being replaced with a mixed polyoxyethylene and polyoxypropylene monostearate (Atlas G 2162) containing 25 oxyethylene units; a degree of conversion of 100 % and an 84 % yield are obtained.

EXAMPLE 10 The procedure is as in Example 7, but instead of filtering after reaction, the crude mixture containing the inorganic salt is distilled.

* A residue of inorganic salts and of inorganic products is obtained, weighing 43 g, and 260 g of distillate containing 55.4 g of benzoyl cyanide, that is an 84.5 % yield.

EXAMPLE 11 The procedure is exactly as in Example 3, but with xylene replaced with an equal volume of toluene.

A degree of conversion of 98.6 % and an 83.2 % yield are obtained.

EXAMPLE 12 The procedure is exactly as in Example 3, but with the addition and the heating being performed at a temperature of 105°C instead of 95°C; a degree of conversion of 99.1 % and an 83.8 % yield are obtained.

EXAMPLE 13 Into a 250-ml round bottomed flask are introduced: 14.7 g of sodium cyanide, 0.2 g of water (0.011 mol), g of xylene, 0.2 g of Antarox 990. .15 g of benzoyl chloride are run in over one hour at 95°C. The reaction is allowed to continue for another 3 hours at 98°C.

The precipitate is removed by filtration and washing with xylene. 15.4 g of salt and 164 g of organic solution are thus collected.

Quantitative analysis of the organic solution by vapour phase chromatography shows that it contains 28.7 g of benzoyl cyanide, which represents an 87.6 % yield relative to the benzoyl chloride used. The degree of conversion of benzoyl chloride is 99 %.

EXAMPLE 14 (COMPARATIVE) The operation is as in Example 13, water being replaced with 2.5 g of benzoic anhydride (0.011 mol).

The degree of conversion of benzoyl chloride is only 19 % and the benzoyl cyanide yield relative to the benzoyl chloride used is only 9.7 %.

EXAMPLE 15 The operation is as in Example 13, with the Antarox being replaced with 0.2 g of polyethylene glycol of average mass 200. After the introduction of benzoyl chloride the mixture is kept at 98°C for 2 hours and at 115°C for 2 hours. The solution obtained after the salt separation contains 29.3 g of benzoyl cyanide which corresponds to an 89.5 % yield relative to the benzoyl chloride used. The degree of conversion of benzoyl chloride is 98 %.

EXAMPLE 16 The operation is as in Example 15, a polyethylene glycol of average mass 3,400 being employed. The degree of conversion of benzoyl chloride is 100 % and the benzoyl cyanide yield is 91.2 % relative to the benzoyl chloride used.

EXAMPLE 17 (applying to a larger quantity) The operation is as in Example 1, all the quantities being multiplied by 8. After the introduction of benzoyl chloride the mixture is kept at 98°C for another 2 hours and at 115 °C for 2 hours.

After the separation of salt the solution is distilled. 234.4 g of benzoyl cyanide are collected, which represents an 89.4 % yield relative to the benzoyl chloride used. The degree of conversion is 100 %.

Claims (15)

1. Process for the synthesis of an acyl cyanide of formula (I): O R-C-CN (I) in which R is an alkyl radical containing from 1 to 8 carbon atoms, a cyeloalkyl radical containing from 3 to 12 carbon atoms, an aryl radical, or a heterocyclic residue which may be condensed with a benzene nucleus, all these radicals R being optionally substituted, which comprises reacting an acid halide of formula (II): II R-C-X (II) in which R is as defined above and X denotes a halogen, with an alkali metal cyanide, in the presence of a product containing alkylene oxide units and a catalytic quantity of water.

2. Process according to claim 1, which is carried out in the presence of a solvent.

3. Process according to claim 2, in which xylene or toluene is employed as solvent.

4. Process according to claim 2 or 3, in which the quantity of solvent is from 150 to 500 ml per mole of acid halide.

5. Process according to any one of claims 1 to 4, in which the alkali metal cyanide is employed in an amount from 1 to 2 moles per mole of acid halide.

6. Process according to claim 5, in which the alkali metal cyanide is employed in an amount from 1 to I. 25 moles per mole of acid halide.

7. Process according to any one of claims 1 to 6, in which sodium cyanide is employed.

8. Process according to any one of claims 1 to 7, in which the product containing alkylene oxide units contains 2 to 200 units which are ethylene oxide and/or propylene oxide units.

9. Process according to any one of claims 1 to 8, in which the quantity of product containing alkylene oxide units is from 0.1 to 10 g per mole of acid halide.

10. Process according to claim 9 in which the quantity of product containing alkylene oxide units is 0.4 to 2g per mole of acid halide.

11. Process according to any one of claims 1 to 10, in which the quantity of water is from 0.2 to 2 g per mole of acid halide.

12. Process according to claim 11, in which the quantity of water is 0.5 to 1 g per mole of acid halide.

13. Process according to any one of claims 1 to II, in which the acid halide is benzoyl chloride.

14. Process according to claim 1, substantially as described in any one of Examples 1 to 3 and 6 to 17.

15. An acyl cyanide whenever synthesised'by a v I process as claimed in any one of claims 1 to 14.