GB1577662A

GB1577662A - Manufacture of glycinonitriles

Info

Publication number: GB1577662A
Application number: GB1905177A
Authority: GB
Original assignee: BASF SE
Current assignee: BASF SE
Priority date: 1976-05-08
Filing date: 1977-05-06
Publication date: 1980-10-29
Also published as: JPS52136124A; FR2350332A2; FR2350332B2; CH624925A5

Abstract

Glycinenitriles of formula I are prepared by reacting a corresponding primary or secondary amine with a carbonyl compound and with hydrogen cyanide in the presence of water. The substituents in formula I have the meaning given in Patent Claim 1. The reaction is carried out for 0.1 to 4 hours at a temperature of 0 to 80 DEG C. The concentration of hydrogen cyanide during the reaction is not more than 0.9% by weight, based on the reaction mixture. The process is suitable for continuous operation on a large industrial scale. No resinous byproducts and discolorations are formed. <IMAGE>

Description

(54) MANUFACTURE OF GLYCINONITRILES (71) We, BASF AKTIENGESELLSHAFT, a German Joint Stock Company of 6700 Ludwigshafen, Federal Republic of Germany, do hereby declare the invention, for which we pray that a Patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following Statement: The present invention relates to a process for the manufacture of a glycinonitrile by reacting an amine with a carbonyl compound and hydrogen cyanide.

German Patent 656,350 discloses that glycollic acid nitrile can be reacted with excess methylamine in aqueous solution under pressure, to give sarcosinonitrile. An excess of up to 10 moles of methyl amine per mole of hydroxyacetonitrile is recommended there in order to achieve good yields of sarcosinonitrile. If stoichiometric amounts are used, considerable amounts of the nitrile of methyldiglycollamic acid are formed, and this compound is difficult to remove.

Another method of preparation of N-alkyl-substituted glycinonitriles uses formaldehyde, in the presence of sodium bisulfite compounds, as the starting material, the aldehyde being reacted with sodium cyanide and aliphatic amines. Using sodium cyanide and sodium bisulfite presents environmental problems when the method is carried out industrially, as a result of the formation of alkali metal salts, which may contain residual cyanides, as by-products. The use of the amines in the form of salts, eg. hydrochlorides has also already been proposed (Jean Mathieu and Jean Weil-Raynal, Formation of C-C Bonds, volume I, pages 442-446 (Georg Thieme Verlag, Stuttgart 1973)).

All these methods are unsatisfactory from the point of view of simple and economical operation, good yields of end product and ease of working up and also in particular in respect of protection of the environment and purificaton of waste water.

German Laid-Open Application DOS 1,543,342 discloses the continuous reaction of aniline with formaldehyde and hydrogen cyanide at from 80 to 1300C, followed by hydrolysis of the reaction mixture with alkali metal hydroxide. Phenylglycinonitrile itself is not isolated. The patent application states that in general less than 10%, and frequently only from 1 to 5%, of the hydrogen cyanide and the formaldehyde are present in the free form in the reaction mixture. In none of the Examples is free hydrogen cyanide used.

The end product obtained from this preparation, especially when carried out on an industrial scale, always contains a substantial proportion of unconverted aniline. When the product is hydrolyzed to give the potassium salt of phenylglycine, this material is again present as an impurity. In the subsequent synthesis of indigo, aniline must be removed, but this is only partially achievable by extraction with an inert solvent, eg. cyclohexane, benzene or toluene. The process is unsatisfactory in that it does not permit simple and economical working up, and does not give a good yield.

Our copending British Patent Applications Nos 3259/76 (Serial No 1526481) and 51643/76 (Serial No. 1560549) disclose and claim a process for the manufacture of an N-substituent glycinonitrile of the formula

where Rl and R2 are identical or different and each is an aliphatic radical, and R2 may also be hydrogen, by reacting formaldehyde with an amine of the formula

where Rl and R2 have the above meanings, and hydrogen cyanide in the presence of water for from 0.1 to 4 hours at from 0 to 80"C, the concentration of hydrocyanic acid during the reaction being not more than 0.1% by weight, based on the reaction mixture.

We have now found that the above process can be extended to provide, according to the present invention, for the manufacture of a glycinonitrile of the formula

where R3, R4, R5 and R6 are identical or different and each is an aromatic, cycloaliphatic or araliphatic radical, R3 and R4 together with the adjacent nitrogen may alternatively form a heterocyclic radical, R4, R5 and R6 may each alternatively be hydrogen, R5 and R6 may each alternatively be an aliphatic radical and R3 and R4 may each alternatively, if R5 and/or R6 are an aliphatic, aromatic, cycloaliphatic or araliphatic radical, be an aliphatic radical, by a process in which an amine of the formula

where R3 and R4 have the above meanings, is reacted with a carbonyl compound of the formula

where R5 and R6 have the above meanings, and hydrogen cyanide in the presence of water for from 0.1 to 4 hours at from 0 to 800C, the concentration of hydrogen cyanide during the reaction being not more than 0.9% by weight, based on the reaction mixture.

Further, we have found that it is advantageous for the resulting glycinonitrile, when it has the formula

where R3, R4, R5 and R" are identical or different and each is an aromatic radical, R5 and R6 may also each be hydrogen or an aliphatic, cycloaliphatic or araliphatic radical and R4 may also by hydrogen, to be treated with an acid at a pH of from 1 to 7 for the purpose of working-up.

Where piperidine and formaldehyde are used, the reaction may be represented by the following equation:

Where acetone and piperidine are used, the reaction may he represented by the following equation:

Where aniline and formaldehyde are used, the reaction may be represented by the following equation:

Compared with the process disclosed in German Laid-Open Application DOS 1,543,342, the process according to the invention is able to give a glycinonitrile more simply and more economically, in better yield and higher purity. The process is particularly suitable for operation on an industrial scale and for continuous operation and presents no substantial waste water problems. Also it gives virtually no resinous by-products and discolorations which tend to be formed at fairly high reaction temperatures with fairly high hydrogen cyanide concentration due to the presence of formaldehyde or of certain other of aldehydes or ketones. The after-treatment avoids expensive purification operations and losses of solvent; since industrial-scale processes using solvent extractions additionally present difficulties with regard to trouble-free operation and control and regulating of off-gas and waste water, the process according to the invention is more reliable in operation and causes less pollution of the environment than certain other known processes.

All these advantages are surprising in view of the prior art.

In various aspects the present invention provides for 1. the use of formaldehyde as the carbonyl compound IV coupled with the use of amines III in which R3 and R4 are identical or different cycloaliphatic or araliphatic radicals or together with the nitrogen atom linking them form a heterocyclic radical and R4 may also be hydrogen, and with an HCN concentration of not more than 0.1% by weight; 2. the use of carbonyl compounds IV other than formaldehyde, coupled with the use of amines III other than aromatic amines and with an HCN concentration of not more than 0.1% by weight; 3. the use of any of the carbonyl compounds IV, coupled with the use of amines III in which R3 is an aromatic radical and R4 is an aromatic radical or hydrogen and with the use of an HCN concentration of not more than 0.1% by weight; and 4. the use of any of the carbonyl compounds IV, coupled with the use of amines III in which R3 is an aromatic radical and R4 is an aromatic radical or hydrogen and with an HCN concentration of more than 0.1% but not more than 0.9% When formaldehyde is used as the carbonyl compound IV it may be used in the liquid form or as a gas, but it is in general used in the form of its aqueous solution, advantageously of from 10 to 50 per cent strength by weight and preferably of from 30 to 40 per cent strength by weight. Hydrogen cyanide may be used as the gas or, advantageously, in the liquid form or in aqueous solution. The starting amine III may be used by itself or in solution; an aliphatic starting amine III is advantageously used in aqueous solution. An aromatic starting amine III may preferably be used by itself, or in solution, advantageously in an organic solvent. The use of solutions of from 40 to 60 per cent strength by weight is advantageous. The three starting materials may be reacted in stoichiometric amounts, or with any of the components in excess; preferably the conditions correspond to an excess, over the stoichiometric amount, of from 0.1 to 5 moles of amine, more preferably from 0.1 to 2 moles of amine in the case of aliphatic amines and from 0.5 to 1 mole of amine in the case of non-aliphatic amines and/or an excess of from 0.01 to 0.1 mole of hydrogen cyanide, in each case per mole of carbonyl compound IV.

Preferred starting materials III and IV and accordingly preferred end products I are those where R3, R4, R5 and R6 are identical or different and each is phenyl, naphthyl, cycloalkyl of 5 to 8 carbon atoms or aralkyl of 7 to 12 carbon atoms; R3 and R4 together with the adjacent nitrogen may alternatively form a 5-membered or 6-membered heterocyclic radical which may contain a further nitrogen or an oxygen; R4, R5 and R6 may alternatively be hydrogen; R5 and R6 may each alternatively be alkyl of 1 to 20, preferably of 1 to 8, and especially of 1 to 4, carbon atoms, or alkenyl of 2 to 20, preferably of 2 to 8, carbon atoms; and R3 and R4 may each alternatively be alkyl of 1 to 20, preferably of 1 to 8, especially of 1 to 4, carbon atoms or alkenyl of 2 to 20, preferably of 2 to 8, carbon atoms if R5 and/or R6 is an aliphatic, aromatic, cycloaliphatic or araliphatic radical. The above radicals may in addition be substituted by one or more groups and/or atoms which are inert under the reaction conditions, eg. nitro, hydroxyl or cyano, or alkyl or alkoxy each of 1 to 4 carbon atoms, or chlorine or bromine which are substituents of a phenyl nucleus.

The following are examples of starting materials IV: formaldehyde, acetaldehyde, propionaldehyde, n-butyraldehyde, iso-butyraldehyde, 2-methylbutyraldehyde, 2ethylcapronaldehyde, n-valeraldehyde, isovaleraldehyde, 2,2-dimethylpropionaldehyde, 2,2-dimethyl-3-hydroxypropionaldehyde, n-capronaldehyde, isocapronaldehyde, 2methylvaleraldehyde, 3-methylvaleraldehyde, 2-ethylbutyraldehyde, 2,2dimethylbutyraldehyde, 2,3-dimethylbutyraldehyde, 3,3-dimethylbutyraldehyde, enanthaldehyde, 2-methylcapronaldehyde, 3-methylcapronaldehyde, 4-methylcapronaldehyde, 5methylcapronaldehyde, 2-ethylvaleraldehyde, 2,2-dimethylvaleraldehyde, 3ethylvaleraldehyde, 3 ,3-dimethylvaleraldehyde, 2,3-dimethylvaleraldehyde, 4ethylvaleraldehyde, 4,4-dimethylvaleraldehyde, 3,4-dimethylvaleraldehyde, 2,4dimethylvaleraldehyde, 2-ethyl-2-methylbutyraldehyde, 2-ethyl-3-methylbutyraldehyde, cyclohexanealdehyde, benzaldehyde, phenylacetaldehyde, acetone, methyl ethyl ketone, methyl n-propyl ketone, methyl isoproyl ketone, methyl n-butyl ketone, methyl sec.-butyl ketone, methyl tert.-butyl ketone, methyl n-pentyl ketone, methyl pentyl-2 ketone, methyl pentyl-3 ketone, methyl isoamyl ketone, methyl (2-methyl)-butyl ketone, methyl (1methyl)-butyl ketone, methyl (2-ethyl)-butyl ketone, methyl (3-ethyl)-butyl ketone, methyl (2,2-dimethyl)-butyl ketone, methyl (2,3-dimethyl)-butyl ketone and methyl (3,3dimethyl)-butyl ketone, corresponding unsymmetrical ketones which contain phenyl, benzyl, cyclohexyl, ethyl, n-propyl, isopropyl or n-butyl instead of methyl; diethyl ketone, di-n-propyl ketone, di-isopropyl ketone. di-n-butyl ketone di-isobutyl ketone, di-sec.-butyl ketone, di-tert.-butyl ketone, di-n-pentyl ketone, dipentyl-2 ketone, dipentyl-3 ketone, diisoamyl ketone, di-(2-methyl)-butyl ketone, di-(1-methyl)-butyl ketone, di-(2-ethyl)butyl ketone, di-(3-ethyl)-butyl ketone, di-(2,2-dimethyl)-butyl ketone, di-(2,3-dimethyl)butyl ketone, di-(3,3-dimethyl)-butyl ketone, dicyclohexyl ketone, dibenzyl ketone and benzophenone.

Examples of starting materials III are methyl-, ethyl-, n-propyl-, ispropyl-, n-butyl-, isobutyl-, sec.-butyl- and tert.-butyl-o-naphthylamine and -(3-naphthylamine, the alkyl substituent being in the 3-, 4-, 5-, 6-, 7-, 8- or 2- or 1- position, preferably in the 2-, 4- or 5-position; corresponding methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec.-butyl and tert.-butyl ethers of the a- and (3-naphthylamines which have a hydroxyl group in the above positions; a- and -naphthylamine disubstituted in the 3,4-, 4,5- 4,8-, 5,8- or 6,7-position by methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl-, sec.-butyl or tert.-butyl; corresponding dihydroxynaphthalenes in which 2 hydroxyl groups in the stated positions are etherified by the above alkyl groups; corresponding a- and -naphthylamines with 2 of the above radicals which are, however, different from one another, eg.

4-ethyl-8-ethoxy-2-naphthylamine and 4-methyl-5-methoxy-1-naphthylamine; 2methylaniline, 3-methylaniline, 4-methylaniline, 2-methoxyaniline, 3-methoxyaniline, 4methoxyaniline, 2.3-dimethylaniline, 3,4-dimethylaniline, 2,6-dimethylaniline, 3,5 dimethylaniline, 2 2.3-dimethoxyaniline, 3,4-dimethoxyaniline, 3 3,5-dimethoxyaniline, 2- ethylaniline, 3-ethylaniline, 4-ethylaniline, 2,3-diethylaniline, 3,4-diethylaniline, 2,6diethylaniline, 3,5-diethylaniline, 2-ethoxyaniline, 3-ethoxyaniline, 4-ethoxyaniline, 2-npropylaniline, 3-n-propylaniline, 4-n-propylaniline, 2,3-di-n-propylaniline, 3,4-di-n- propylaniline, 2.6-di-n-propylaniline, 3,5-di-n-propylaniline, 2-isopropylaniline, 3isopropylaniline, 4-isopropylaniline, 2-butylaniline, 3-butylaniline, 4-butylaniline, 2isobutylaniline, 3-isobutylaniline, 4-isobutylaniline, 2-tert. -butylaniline, 3-tert.butylaniline, 4-tert.-butylaniline, 2,3-diethoxyaniline, 3,4-diethoxyaniline, 2,6diethoxyaniline, 3,5-diethoxyaniline, 2,3,4-, 3,4,5-, 2,4,6-, 2,3,6- and 2,3,5trimethylaniline, 2,3,4- 3,4,5-, 2,4,6-, 2,3,6- and 2,3,5-trimethoxyaniline, 2,3,4-, 3,4,5-, 2,4,6-, 2,3,6- and 2.3,5-triethylaniline and 2,3,4-, 3,4,5-, 2,4,6-, 2,3,6- and 2,3,5triethoxyaniline; anilines monosubstituted or polysubstituted in the above positions by hydroxyl, nitro, chlorine and/or bromine instead of the above alkyl substituents or together with the above alkyl substituents; and N-arylamines disubstituted by the above phenyl radicals and/or naphthyl radicals diphenylamine, a-naphthylamine, B-naphthylamine, aor -naphthylamine substituted respectively in the 2- or 1-position, or in the 4-position, by methyl, ethyl or n-propyl. 2-methylaniline. 3-methylaniline, 4-methylaniline, 2,3 dimethylaniline, 3,4-dimethylaniline and especially aniline are preferred.

Further starting materials III are methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine, isobutylamine, sec.-butylamine, tert.-butylamine, pentylamine, pentyl-2-amine, pentyl-3-amine, n-hexylamine, n-heptylamine, n-octylamine, n-nonylamine, n-decylamine, n-tridecylamine, n-octadecylamine, oleylamine, 2-ethylhexylamine, 2ethylpentylamine, 3-ethylpentylamine and 4-methylheptylamine; dimethylamine, diethylamine, di-n-propylamine, diisopropylamine, di-n-butylamine, diisobutylamine, di-sec.butylamine, di-tert.-butylamine, dipentylamine, di-(pentyl-2)-amine, di-(pentyl-3-amine, di-n-hexylamine, di-n-heptylamine, di-n-octylamine, di-n-nonylamine, di-n-decylamine, di-2-ethylhexylamine and di-4-methylheptylamine; corresponding amines with 2 of the above radicals which, however, are different from one another, eg. methylethylamine; cyclohexylamine, cyclopentylamine, cycloheptylamine, benzylamine and phenylethylamine; dicyclohexylamine, dicyclopentylamine, dicycloheptylamine, dibenzylamine and diphenylethylamine; pyrrolidine, A2-pyrroline, A3-pyrroline, pyrrole, pyrazole, pyrazoline, pyrazolidine, imidazolidine, hexamethyleneimine, 3-imidazoline, piperidine, morpholine, piperazine, indoline, indole, isoindoline, isoindole, indazole, benzimidazole, 1,2,3,4tetrahydroisoquinoline, carbazole, phenoxazine, 4-methylimidazole, 2-methylindole, 3methylindole, 2-methylpiperazine, 3-methylpyrrole, 2-methylpyrrole, 2-ethylmorpholine, 2-ethylpiperidine and 2-methylpyrrolidine.

The reaction is carried out at from 0 to 80"C, irrespective of the nature of the amines. For aromatic amines it is advantageous to use a temperature from 40 to 80"C, preferably from 45 to 75"C and especially from 50 to 700C, and in the case of non-aromatic amines it is advantageous to use a temperature of 10 to 80"C, preferably from 10 to 65"C and especially from 15 to 400C. The reaction may be carried out under reduced pressure, superatmospheric pressure or, preferably, atmospheric pressure, batchwise or, preferably, continuously.

Water is advantageously used in the form of aqueous formaldehyde solution and/or an aqueous amine solution and in addition water is formed in the reaction itself; a total of from 1 to 6, preferably from 3 to 4, moles of water, per mole of carbonyl compound IV, are advantageously used. Hydrogen cyanide is added to the starting mixture, before or during the reaction, in an amount such that the concentration of hydrogen cyanide, based on the reaction mixture during the reaction, does not exceed 0.9 per cent by weight, and is in general from 0.01 to 0.9, advantageously from 0.01 to 0.8, more particularly from 0.01 to 0.7, preferably from 0.01 to 0.1 and especially from 0.05 to 0.1 per cent by weight. The reaction time (or, in continuous operation, the residence time) is from 0.1 to 4 hours preferably from 1 to 2 hours. The use of water as the sole solvent is preferred, but a organic solvent which is inert under the reaction conditions may also be present. Examples of suitable solvents are aromatic hydrocarbons, eg. toluene, benzene, ethylbenzene, o-, mand p-xylene, isopropylbenzene and methylnaphthalene; aliphatic or cycloaliphatic hydrocarbons, eg. heptane, a-pinene, pinane, nonane, gasoline fractions within a boiling range of from 70 to 1900C, cyclohexane, methylcyclohexane, petroleum ether, decalin, hexane, naphtha, 2,2 ,4-trimethylpentane, 2,2,3-trimethylpentane, 2,3 ,3-trimethylpentane and octane; and corresponding mixtures. The organic solvent is advantageously used in amount of from 40 to 10,000 per cent by weight, preferably from 50 to 500 per cent by weight, based on starting material III.

Organic solvents which are inert under the reaction conditions are specifically superfluous in the case of aromatic amines.

The reaction may be carried out as follows: a mixture of the carbonyl compound IV, water, hydrogen cyanide and starting amine III, with or without an organic solvent, is kept at the reaction temperature for the reaction time. Some of the hydrogen cyanide is introduced into the starting mixture and some is added during the reaction, in portions or continuously, so that the concentration of hydrogen cyanide is maintained at or below 0.9% by weight during the entire reaction time. The continuous measurement of the hydrogen cyanide concentration is advantageously carried out by means of a silver/calomel electrode.

The end product may then be isolated from the reaction mixture by a conventional method, eg. by removing the organic phase and distilling it, or by filtration, or by extraction, eg. with cyclohexane or ethyl acetate, followed by distillation of the solvent.

In a preferred method of working up, in the case of aromatic glycinonitriles, the treatment of the reaction mixture after the reaction is carried out in the presence of acid, advantageously using from 0.01 to 2, especially from 0.1 to 0.5, equivalents of the acid per mole of starting material 1II. Inorganic or organic acids may be used and monobasic acids or equivalent amounts of polybasic acids may be employed. Examples of acids which may be used are: hydrogen chloride, hydrogen bromide, hydrogen iodide, perchloric acid, sulfuric acid, phosphoric acid, nitric acid and carbonic acid; sulfonic acids, eg. benzenesulfonic acid and p-toluenesulfonic acid; boron-containing acids, eg. boric acid and fluoboric acid; aliphatic carboxylic acids, eg. chloroacetic acid, dichloroacetic acid, trichloracetic acid, acrylic acid, oxalic acid, formic acid, cyanoacetic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, tetracosanoic acid, hexacosanoic acid, linoleic acid, linolenic acid, ricinoleic acid, erucic acid, myristic acid, arachidic acid, behenic acid, oleic acid, elaidic acid, caproic acid, enanthic acid, pelargonic acid, capric acid, 3,5,5-trimethylhexanoic acid, 2-ethylpent-2-en-1-oic acid, undecylic acid, lauric acid, palmitic acid, stearic acid, 2-ethylhexanecarboxylic acid, a-ethylbutyric acid, methacrylic acid, crotonic acid, isocrotonic acid, tiglic acid, sorbic acid, undecylenic acid, 2-methylbutanoic acid, glycollic acid, lactic acid, pyruvic acid, acetoacetic acid, levulic acid, monobromoacetic acid, tartaric acid, citric acid, -hydroxybutyric acid, caprylic acid, trimethylacetic acid, a- and p- chloropropionic acid, succinic acid, malonic acid, isovaleric acid, valeric acid, glutaric acid, adipic acid and maleic acid; cycloaliphatic, araliphatic and aromatic carboxylic acids, eg.

benzoic acid, 2,3-, 2,4-, 2,5- and 2,6-dimethylbenzoic acid, o-,m- and p-aminobenzoic acid, o-, m- and p-hydroxybenzoic acid, mellitic acid, phenylpropionic acid, o-, m- and p-chlorobenzoic acid, cyclohexanecarboxylic acid, cyclopentanecarboxylic acid, phenylacetic acid, a- and -naphthoic acid, 2,3-hydroxynaphthoic acid, cinnamic acid, naphthalene1,8-dicarboxylic acid, phthalic acid, o-, m- and p-toluic acid, o-, m- and p-nitrohenzoic acid, isophthalic acid and terephthalic acid; ethylenediaminetetraacetic acid, nitrilotriacetic acid, diethylenetriaminepentaacetic acid, diglycollic acid, thiodiglycollic acid and sulfonediacetic acid; acid ion exchangers; and appropriate mixtures. The acids may be used in a concentrated form, or as mixtures with one another and/or with a solvent, especially with water. Amongst dilute aqueous acids, those of from 0.1 to 50 per cent strength by weight, eg. hydrochloric acid of from 1 to 10 per cent strength by weight, sulfuric acid of from 1 to 25 per cent strength by weight or phosphoric acid of from 1 to 10 per cent strength by weight, are advantageously used. Hydrochloric acid, sulfuric acid, phosphoric acid, p-toluenesulfonic acid, oxalic acid, formic acid, acetic acid, monochloroacetic acid, dichloroacetic acid and trichloroacetic acid are preferred. The treatment with acid is carried out at a pH of from 1 to 7, preferably from 2 to 5, especially from 2 to 3.

In the case of the aromatic glycinonitriles the end product can be isolated from the reaction mixture by a conventional method. eg. by distillation, and can then be treated with acid, advantageously together with water, at the above pH, advantageously at from 0 to 90"C, preferably from 15 to 70"C, under atmospheric or superatmospheric pressure, continuously or batchwise, for from 5 to 30 minutes, with thorough mixing. In such cases, it is preferred to use from 0.01 to 0.5, preferably from 0.1 to 0.5, equivalent of acid and from 0.1 to 5, advantageously from 1 to 3, moles of water, per mole of starting material III; a ratio of from 0.05 to 0.2 equivalent of acid per mole of water is advantageous. During the treatment, surprisingly, the aniline in particular dissolves, whilst the N-arylglycinonitrile with a secondary or tertiary nitrogen does not dissolve to a substantial degree.

In a preferred embodiment, the treatment of the reaction mixture is carried out after one or more working-up operations, eg. after one or more passes through a working-up unit such as a stirred kettle or reactor. or, advantageously, directly after the reaction. The reaction mixture which has been partially worked up, or not yet worked up at all, is advantageously mixed with the above amount of acid, with or without from 5 to 58 per cent by weight of water, based on the reaction mixture, the pH and the temperature are brought to the values given above for carrying out the treatment, and the mixture is kept under these treatment conditions, advantageously for from 5 to 30 minutes, under atmospheric or superatmospheric pressure, the operation being carried out continuously or batchwise. The end product may then be isolated from the mixture by conventional methods, eg. by distillation, filtration or phase separation.

Glycinonitriles obtainable by the process of the invention find use as antioxidants and/or as starting materials for the manufacture of dyes, fungicides, bactericides, textile auxiliaries and inhibitors for use in antifreezes. On hydrolysis, eg. with alkali metal hydroxide solutions, they give alkali metal salts of the corresponding glycine which, especially in the case of a-unsubstituted glycinonitriles, are selective absorbents for CO2, SO2 and H7S.

Hydrogenation of the glycinonitriles gives asymmetrical diamines which are valuable starting materials for drugs and crop protection agents.

Alkali metal salts of phenylglycine are used as starting materials for the synthesis of indigo. With regard to the use of the compounds, reference may be made to the above German Laid-Open Application and to Ullmanns Encyklop die der technischen Chemie, volume 9, page 388, volume 15, page 219, and volume 19, pages 300, 317 and 339.

In the Examples which follow, parts are by weight.

Example 1 Per hour. 400 parts of a 30 per cent strength by weight aqueous formaldehyde solution, 108 parts of hydrogen cyanide and 340 parts of piperidine are slowly mixed in a stirred kettle at 20"C; during the reaction the hydrogen cyanide concentration does not exceed 0.1 per cent by weight, based on the total mixture, and averages from 0.08 to 0.09 per cent by weight. The total reaction time is one hour. Per hour, 848 parts of reaction mixture are obtained. This mixture separates into 2 phases, and after separating off the organic phase 485 parts of piperidinyl acetonitrile (98% of theory) of boiling point 98"C/18 mm Hg, and with no2C = 1.4592, are obtained.

Example 2 400 parts of a 30 per cent strength by weight aqueous formaldehyde solution, 108 parts of hydrogen cyanide and 396 parts of cyclohexylamine are slowly mixed in a stirred vessel at 25"C; during the reaction the hydrogen cyanide concentration does not exceed 0.1 per cent by weight, based on the total mixture, and averages 0.08 per cent by weight. The total reaction time is one hour. Per hour, 532 parts of cyclohexylglycinonitrile (96% of theory), of n020 = 1.4670, are obtained by the method described in Example 1.

Example 3 Using the method described in Example 1, 1,566 parts of morpholine, 1,800 parts of a 30 per cent strength by weight aqueous formaldehyde solution and 486 parts of liquid hydrogen cyanide per hour are mixed in a stirred kettle at 180C; the hydrogen cyanide concentration does not exceed 0.1 per cent by weight, based on the total mixture, and averages 0.08 per cent by weight. In a downstream reaction vessel, the mixture is allowed to continue to react for a further hour at 300C. The total reaction time is 2 hours. After cooling to 0 C, N-morpholinylacetonitrile precipitates, and is filtered off. Per hour, 1,810 parts of N-morpholinylacetonitrile (80% of theory) of melting point 55-57"C are obtained.

Example 4 Using the method described in Example 1, 1,278 parts of pyrrolidine, 1,800 parts of a 30 per cent strength by weight aqueous formaldehyde solution and 486 parts of liquid hydrogen cyanide per hour are mixed in a stirred kettle at 200C; the hydrogen cyanide concentration does not exceed 0.1 per cent by weight, based on the total mixture, and averages 0.08 per cent by weight. The mixture is allowed to react for a further hour at 450C.

The total reaction time is 2 hours. The reaction mixture is heated at 60"C, 350 parts of soda being added simultaneously. The organic phase is separated off, and 1910 parts (95% of theory) of N-pyrrolidinoacetonitrile of boiling point 111 C/60 mm Hg and with n020 = 1.4557 are obtained per hour.

Example 5 Using the method described in Example 1, 214 parts of benzylamine, 200 parts of a 30 per cent strength by weight aqueous formaldehyde solution and 54 parts of liquid hydrogen cyanide per hour are mixed in a stirred kettle at 20do; the hydrogen cyanide concentration does not exceed 0.1 per cent by weight, based on the total mixture, and averages 0.08 per cent by weight. The reaction mixture is then allowed to react for a further hour at 450C. The total reaction tim 1,296 parts of n-butyraldehyde and 486 parts of liquid hydrogen cyanide per hour are slowly mixed in a stirred kettle at 27"C; during the reaction the hydrogen cyanide concentration does not exceed 0.1 per cent by weight, based on the total mixture, and averages 0.085 per cent by weight. The mixture is allowed to react for a further 2 hours at 30"C in a downstream kettle. The total reaction time is 3 hours. The upper organic phase which forms is separated off and distilled. Per hour, 2980 parts (99% of theory) of piperidino-a-(propyl) acetonitrile of boiling point 52"C/0.02 mbar, and with n020 = 1,4617, are obtained.

Example 9 Using the method described in Example 6, 370 parts of n-dodecylamine, 212 parts of benzaldehyde, 50 parts of water and 54 parts of hydrogen cyanide per hour are slowly mixed in a stirred kettle at 45"C; during the reaction the hydrogen cyanide concentration does not exceed 0.1 per cent by weight, based on the total mixture, and averages 0.085 per cent by weight. The mixture is allowed to react for a further 21/2 hours at 55"C in a downstream kettle. The total reaction time is 31/2 hours. The upper organic phase which has formed is separated off at 550C, and is distilled. Following the method described in Example 6, 586 parts (97% of theory) of a-phenyl-N-n-dodecyl-aminoacetonitrile, with nD = 1.4928, are obtained per hour.

Example 10 Using the method described in Example 6, 370 parts of n-dodecylamine, 144 parts of n-butyraldehyde, 50 parts of water and 54 parts of liquid hydrogen cyanide per hour are slowly mixed in a stirred kettle at 55"C; during the reaction the hydrogen cyanide concentration does not exceed 0.1 per cent by weight, based on the total mixture, and averages 0.085 per cent by weight. The mixture is allowed to react for a further 2l/2 hours at 50"C in a downstream kettle. The total reaction time is 31/2 hours. The organic upper phase is separated off. After extraction with 300 parts of ethyl acetate, using the method described in Example 6, 520 parts (97% of theory) of N-n-dodecylamino-a-n-propylacetonitrile, with nr20 = 1.4505, are obtained.

Example 11 Per hour, 400 parts of 30 per cent strength by weight aqueous formaldehyde solution, 108 parts of liquid hydrogen cyanide and 372 parts of aniline are slowly mixed in a stirred kettle at 65"C; the hydrogen cyanide concentration in the reaction space does not exceed 0.1 per cent by weight (based on the reaction mixture), and averages 0.08 per cent by weight. After a mean residence time of 60 minutes, the reaction mixture is passed into a reactor which is at 65"C. The mean residence time in the reactor is 45 minutes and the average hydrogen cyanide concentration is 0.04 per cent by weight. Per hour, 880 parts of a reaction mixture are obtained; this is extracted with benzene and after evaporation of the benzene gives, per hour, 512 parts (98% of theory) of phenylglycinonitrile of n5" = 1.5591 and melting point 40-42"C (after recrystallization from a 1:1 mixture of cyclohexane and isopropanol).

Example 12 Per hour, 400 parts of 30 per cent strength by weight aqueous formaldehyde solution, 108 parts of liquid hydrogen cyanide and 372 parts of aniline are slowly mixed in a stirred kettle at 65"C; the hydrogen cyanide concentration in the reaction space does not exceed 0.9 per cent by weight (based on the reaction mixture), and averages 0.8 per cent by weight. After a mean residence time of 60 minutes. the reaction mixture is passed into a reactor which is at 65"C. The mean residence time in the reactor is 45 minutes and the average hydrogen cyanide concentration is 0.5 per cent by weight. Per hour, 880 parts of a reaction mixture are obtained; this is extracted with benzene and after evaporation of the benzene gives, per hour, 512 parts (98cue of theory) of phenylglycinonitrile of nD" = 1.5591 and melting point 40-42"C (after recrystallization from a 1:1 mixture of cyclohexane and isopropanol).

Example 13 Per hour, 400 parts of 30 per cent strength by weight aqueous formaldehyde solution, 108 parts of liquid hydrogen cyanide and 372 parts of aniline are slowly mixed in a stirred kettle at 65"C; the hydrogen cyanide concentration in the reaction space does not exceed 0.1 per cent by weight (based on the reaction mixture), and averages 0.08 per cent by weight. After a mean residence time of 60 minutes, the reaction mixture is passed into a reactor which is at 65"C. The mean residence time in the reactor is 45 minutes and the average hydrogen cyanide concentration is 0.04 per cent by weight. Per hour, 880 parts of a reaction mixture are obtained and. in a second stirred kettle. 57 parts per hour of 12.8 per cent strength by weight hydrochloric acid are added to the reaction mixture and the batch is kept at pH 2, the mean residence time in the second stirred kettle being 25 minutes at 65"C. The batch is then separated in a separator, giving, per hour, 523 parts (99% of theory) of phenylglycinonitrile of nD = 1.5591 and melting point = 42"C (after recrystallization from a 1:1 mixture of cyclohexane and isopropanol).

We are aware of the Carcinogenic Substances Regulations 1967 and we make no claim to the use of the invention in contravention of the law.

WHAT WE CLAIM IS: 1. A process for the manufacture of a glycinonitrile of the formula

where R3, R4, R5 and R6 are identical or different and each is an aromatic, cycloaliphatic or araliphatic radical, R3 and R4 together with the adjacent nitrogen may alternatively form a heterocyclic radical, R4, R5 and R6 may each alternatively be hydrogen, R5 and R6 may each alternatively be an aliphatic radical and R3 and R4 may each alternatively, if R5 and/or R6 are an aliphatic, aromatic, cycloaliphatic or araliphatic radical, be an aliphatic radical, wherein an amine of the formula

where R5 and R6 have the above meanings, and hydrogen cyanide in the presence of water for from 0.1 to 4 hours at from 0 to 80"C, the concentration of hydrogen cyanide during the reaction being not more than 0.9% by weight, based on the reaction mixture.

2. A process as claimed in claim 1 for the manufacture of a glycinonitrile of the formula I given in claim 1 in which R3is an aromatic radical, R4 is hydrogen or an aromatic radical and R5 and R6, which are identical or different, are each hydrogen or an aliphatic, cycloaliphatic, araliphatic or aromatic radical wherein, for working up, the glycinonitrile I is treated with an acid at a pH of from 1 to 7.

3. A process as claimed in claim 1 or 2, in which the reaction is carried out with an excess, over the stoichiometric amount, of from 0.1 to 5 moles of amine III per mole of carbonyl compound IV.

4. A process as claimed in claim 1 or 2, in which an aliphatic amine III is used and the reaction is carried out with an excess, over the stoichiometric amount, of from 0.1 to 2 moles of amine per mole of carbonyl compound IV.

5. A process as claimed in claim 1 or 2, in which a non-aliphatic amine III is used and the reaction is carried out with an excess, over the stoichiometric amount, of from 0.5 to 1 mole of amine per mole of carbonyl compound IV.

6. A process as claimed in any of claims 1 to 5, in which the reaction is carried out with from 0.01 to 0.1 mole of hydrogen cyanide per mole of carbonyl compound IV.

7. A process as claimed in any of claims 1 to 6, in which the reaction is carried out with an aromatic amine at from 40 to 80"C.

8. A process as claimed in claim 7, in which the reaction is carried out at from 45 to 75"C.

9. A process as claimed in any of claims 1 or 3 to 6, in which the reaction is carried out with a non-aromatic amine at from 10 to 800C.

10. A process as claimed in claim 9, in which the reaction is carried out at from 10 to 65"C.

11. A process as claimed in any of claims 1 to 10, in which the reaction is carried out with a total amount of from 1 to 6 moles of water per mole of carbonyl compound IV.

12. A process as claimed in any of claims 1 to 11, in which the reaction is carried out with a concentration, during the reaction, of from 0.01 to 0.9% by weight of hydrogen cyanide, based on the reaction mixture.

**WARNING** end of DESC field may overlap start of CLMS **.

Claims

**WARNING** start of CLMS field may overlap end of DESC **. the mean residence time in the second stirred kettle being 25 minutes at 65"C. The batch is then separated in a separator, giving, per hour, 523 parts (99% of theory) of phenylglycinonitrile of nD = 1.5591 and melting point = 42"C (after recrystallization from a 1:1 mixture of cyclohexane and isopropanol). We are aware of the Carcinogenic Substances Regulations 1967 and we make no claim to the use of the invention in contravention of the law. WHAT WE CLAIM IS:

1. A process for the manufacture of a glycinonitrile of the formula

13. A process as claimed in any of claims 1 to 11, in which the reaction is carried out

with a concentration, during the reaction. of from 0.01 to 0.7% by weight of hydrogen cyanide, based on the reaction mixture.

14. A process as claimed in any of claims 1 to 11, in which the reaction is carried out with a concentration, during the reaction, of from 0.01 to 0.1% by weight of hydrogen cyanide, based on the reaction mixture.

15. A process as claimed in any of claims 1 to 11, in which the reaction is carried out with a concentration, during the reaction, of from 0.05 to 0.1% by weight of hydrogen cyanide, based on the reaction mixture.

16. A process as claimed in any of claims 1 to 15, in which the reaction is carried out for from 1 to 2 hours.

17. A process as claimed in claim 2 or in any one of claims 3 to 8 or 11 to 16 appendant to claim 2, in which the treatment with acid is carried out with from 0.01 to 2 equivalents of acid per mole of starting material III.

18. A process as claimed in claim 2 or in any of claims 3 to 8 or 11 to 17 appendant to claim 2, in which the treatment with acid is carried out at a pH of from 2 to 5.

19. A process as claimed in any of claims 1 to 18, wherein the carbonyl compound is formaldehyde.

20. A process as claimed in any of claims 1 to 18, wherein the carbonyl compound is an aldehyde, R6 being hydrogen and R5 being phenyl, naphthyl, cycloalkyl of 5 to 8 carbon atoms, aralkyl of 7 to 12 carbon atoms, alkyl of 1 to 8 carbon atoms or alkenyl of 2 to 8 carbon atoms.

21. A process as claimed in any of claims 1 to 18, wherein the carbonyl compound is a ketone, R > having the meaning given in claim 20 and R6 being selected from the alternatives specified for R5 in claim 20.

22. A process as claimed in any of claims 1 to 21, wherein the amine is a primary amine, R4 being hydrogen and R3 being phenyl, naphthyl, cycloalkyl of 5 to 8 carbon atoms or aralkyl of 7 to 12 carbon atoms, or is a secondary amine, R3 and R4 being selected independently from the alternatives specified for R3 above or R3 and R4 together forming with the adjacent nitrogen atom a 5-membered or 6 membered heterocyclic ring which may contain an oxygen atom or a further nitrogen atom.

23. A process as claimed in claim 20 or 21, wherein the amine is a primary or secondary amine in which R3 is alkyl of 1 to 8 carbon atoms or alkenyl of 2 to 8 carbon atoms and R4 is hydrogen. alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, phenyl, naphthyl, cycloalkyl of 5 to 8 carbon atoms or aralkyl of 7 to 12 carbon atoms.

24. A process as claimed in claim 1, wherein the carbonyl compound IV is formaldehyde, R3 and R4 are identical or different cycloaliphatic or araliphatic radicals or together with the nitrogen atom linking them form a heterocyclic radical and R4 may also be hydrogen, and the HCN concentration is not more than 0.1% by weight.

25. A process as claimed in claim 1, wherein carbonyl compound IV is other than formaldehyde, amine III is other than an aromatic amine and the HCN concentration is not more than 0.1% by weight.

26. A process as claimed in claim 1, wherein R3 is an aromatic radical and R4is an aromatic radical or hydrogen and the HCN concentration is not more than 0.1% by weight

27. A process as claimed in claim 1, wherein R3 is an aromatic radical and R is an aromatic radical or hydrogen and the HCN concentration is more than 0.1% but not more than 0.9%.

28. A process for the manufacture of a glycinonitrile carried out substantially as described in any of the foregoing Examples.

29. Glycinonitriles when manufactured by a process as claimed in any of claims 1 to 24.