Processing method of aminomethylfosfone acid

The invention relates to a process for the preparation of aminomethylphosphonic acid of the formula I

About OH \\ 7

HzN — CH2 —P \

OH '(I)

Aminomethylphosphonic acid has hitherto been described both as an active ingredient for influencing plant growth (cf. DOS No. 2 315 886) and as an intermediate for the production of herbicidally active substances (cf. DOS No. 2 555 573).

It has already been proposed to produce aminomethylphosphonic acid by reacting N-hydroxymethylamide of a carboxylic acid with phosphorus trichloride or trialkyl phosphite followed by hydrolysis of the reaction product [see U.S. Pat. No. 2,304,156 and 2,328,358 and Bull. Akad. Sci. (USSR) 1988, 585].

Another known method of preparing this compound is based on the reaction of N-biomethylphthalimide with sodium diethylphosphite or triethylphosphite and subsequent hydrolysis of phthalimidomethylphosphonic acid diethyl ester [see Bull. Soc. Chim. (France) 778

I (1948) Ann. Chim. (Paris) (12) 4,372 (1954), J. Amer. Chem. Soc. 75, 5278 (1953); J. Chem. Soc. (c), 1349 (19613)].

It is also known to produce aminomethylphosphonic acid by reacting O, O-diethyl halomethylphosphonates with ammonia followed by hydrolysis of the reaction product [cf. CA 45, 8444 (1951), ibid. 46, 421 (1952), ibid. 48, 564 (1954)], or by reaction of chloromethylphosphonic acid with ammonia (see DOS No. 2,315,886).

Furthermore, it has been proposed to produce aminomethyl phosphonic acid by Curtiic degradation of α-β-β-β-β-β-β-β-β-β-α-β-β-β-β-β-β-β-β-β-β-β. 832 (1964)].

Also known is a process for the preparation of aminomethylCosConic acid by first reacting tert-butylamine with formaldehyde to form the corresponding Schiff base (N-methyl-tert-butylamine), which base is converted to N- by addition of phosphorous diester tert-butylaminomethylphosphate, from which the tert-butyl group is cleaved off under drastic reaction conditions by treatment with hydrogen bromide while hydrolyzing the ester groups [see Synth. Inorg. Metal Org. Chem. 2, 317 (1972)].

Another known process for the preparation of aminomethylphosphinic acid consists in reacting dibenzylamine with formaldehyde and an ester of phosphorous acid to form N, N-dibenzylaminomethylphosphonate, hydrolyzing the compound and subsequent hydrogenolytic cleavage of N-benzyl groups. An alternative to this process is the process wherein Ν, Ν-dibenzylaminomethylphosphonic acid formed as an intermediate in this synthesis is obtained by reacting dibenzylamine with chloroacetic acid resulting in N, N-dibenzylglycine, and subsequently reacting it with phosphorous trichloride and phosphorous acid and N-benzyl groups are also extracted from the resulting intermediate by hydrogenolysis [see Phosiphorus and Sulfur 7, 333 (1979)].

In accordance with another known method, acetonitrile with formaldehyde (paraformaldehyde) is reacted with phosphoric acid and phosphorus trichloride, and the reaction product is converted to N-acetylaminomethylphosphonic acid by further reaction with water which, after subsequent hydrolytic cleavage of the acetyl group, provides aminomethylphosphine. acid (see DOS No. 2,829,046).

There is also known a process for the preparation of aminomethylphosphonic acid, wherein benzylurethane is converted by heating with acetic anhydride and paraformaldehyde in acetic acid to N-acetyl-benzylurethane. , this is reacted with triphenyl phosphite. to give N- (O, O-diphenylphenylmethyl) benzylurethane, from which the benzyloxycarbonyl group is cleaved by hydrolysis (see Synthesis 1980, 906).

Using the above processes, it is not possible to produce aminomethylphosphonic acid on an industrial scale with a satisfactory yield. Neither of these methods yields a total yield of more than 70% of theory. In most cases, the overall yield ranges from 20 to 50% of theory. Some of the above processes are also disadvantageous because they use costly and difficult to access starting materials. Moreover, in certain cases, it is necessary to work under extreme reaction conditions, which entails the need to spend considerable resources on the equipment.

The object of the invention, on the other hand, is a process which starts from readily available starting materials and which makes it possible to produce aminomethylphosphonic acid in a simple manner - and in a satisfactory yield.

It has been found that aminomethylphosphonic acid can be produced simply and in good yield by the hexahydro-1H-triazine-N, N, N-tris-carboxylic acid ester of formula II

COOR

AND

ROOC-N-H-COOR (II) wherein

R is C 1 -C 4 alkyl or phenyl, reacted at a temperature of from 90 to 150 ° C in the presence of a Lewis acid catalyst with a phosphorous ester of formula III

O ORi

Η — P \

ORi (III) wherein

R 1 represents a C 1 -C 5 asylum group, a phenyl group, a benzyl group, a 2-cyanethyl group or a 2,2,2-trichloroethyl group, to give the N-carbonylaminomethylphenylphosphonic acid derivative of the general formula IV

OO ORi

II II /

RO-C-NH-CH2-P

X

ORi (IV) wherein

R and R 1 are as defined above, and this derivative is then hydrolyzed in an aqueous medium in the presence of a strong acid to form amine methylphosphonic acid.

The hexalhydro-1H-triazine-N, LN-tris-carboxylic acid esters of formula II which are required as starting materials in the process of the present invention can be prepared in a simple manner - and - in excellent yield by the reactions corresponding to - urethane and formaldehyde in aqueous hydrochloric acid [see J. Amer. Chem. Soc. 68, 1681 (1946)] or by reaction of urethane with paraformal chloride - in the presence of p-toluenesulfonic acid as a catalyst and in toluene as a solvent [see J. Heterccycl. Chem., 11, 937 (1974)]. From the thus obtained esters of hexalhydro-1,4-triazine

G

WITH

-N, N ', N'-tris-carboxylic acids of the formula II are particularly suitable starting materials for the process according to the invention those compounds in which R represents a methyl or ethyl group.

Suitable Lewisic acids which catalyze the reaction of hexahydro-1,3,5-triazine-N, N ', N'-tris-carboxylic acid esters of formula II with the phosphorous esters of formula III within the meaning of the invention are boron trifluoride etherate , titanium tetrachloride, tin tetrachloride, ferric chloride and aluminum chloride. Boron trifluoride etherate has proven to be a particularly suitable catalyst. The Lewis acids are generally used in an amount of from 1 to 10 mol. %, Based on the hexahydric-1,3-triazine N, N ', N' -tris-carboxylic acid ester of formula II. Preferably, the Lewis acids are used in an amount of from 4 to 6 mol. %, Based on ester hex^!ahydro-1,3,5-triazine N, N ', N' -tris-carboxylic acid of formula II.

The reaction of the hexahydro-1,3,5-triazine-N, N ', N'-tris-carboxylic acid ester of formula II with a phosphorous ester of formula III can be carried out either in the presence or absence of an inert solvent. Suitable solvents are, for example, hydrocarbons and halogenated hydrocarbons boiling at least 110 ° C, such as toluene, xylene, chlorobenzene and o-dichlorobenzene.

Within a given temperature range of 90 to 150 cc, the reaction of the hexahydro-1,3,5-triazine-N, N ', N'-tris-carboxylic acid ester of formula II with the phosphorous acid ester of formula III according to the invention can be carried out temperatures of from 120 to 150 ° C are preferred.

Preferred are those phosphorous acid esters of formula III wherein R 1 is C 1 -C 3 alkyl. However, the bis- (2-cyanoethyl) ester and the bis- (2,2,2-trichloroethyl) phosphorous acid ester are also very suitable, since the 2-cyanethyl and 2,2,2-trichloroethyl groups are it is particularly easy to cleave hydrolytically.

Hexahydrol esters, 3,5-triazine N, N ', N'

The tris-carboxylic acids of the formula II and the phosphorous esters of the formula III are generally reacted with one another in a stoichiometric ratio. In practice, it has proven advantageous to use a slight excess of the phosphorous acid ester of the formula III, up to 10 mol. ° / o.

The aqueous reaction medium used to hydrolyze the N-carboxy-aminomethylphosphonic acid derivative of the formula IV obtained by reacting a hexahydro-1,3,5-triazine-N, N ', N'-tris-carboxylic acid ester of the formula II with a phosphorous ester of formula III may be either water or a mixture of water and an organic solvent, for example a mixture of water with acetonitrile, methanol or ethanol. Useful strong acids are, for example, hydrochloric acid, hydrobromic acid. hydroiodic acid, sulfuric acid, phosphoric acid and p-toluenesulfonic acid. Particularly suitable are hydrohalic acids, in particular hydrochloric acid and hydrobromic acid. The hydrolysis of the N-carboxy-aminomethylphosphonic acid derivative of the general formula (IV) is carried out at elevated temperature, preferably under reflux.

The alkyl groups R and R 1 may have a straight or branched chain. The phenyl group R or R 1 may either be unsubstituted or be substituted by substituents inert to the reactants such as halogen atoms, lower alkyl groups, alkoxy groups, cyano and nitro groups. The same applies to the phenyl group of the benzyl radical as defined by R1.

In accordance with a preferred embodiment of the process according to the invention, the aminomethylphosphonic acid is produced by producing the ester of hexahydrate Ot1, 3,5-triazine-N, N^<, N^atThe tri-carboxylic acid of the formula (II) in which R represents a methyl or ethyl group leaves in the presence of 4 to 6 mol. % boron trifluoride etherate, based on the hexahydro-1,3,5-triazine-N, N ester used^Ť, N '^<- a tris-carboxylic acid of the formula II, at 120 to 150 ° C, to react with a phosphorous acid ester of the formula III in which R 1 represents an alkyl group having 1 to 3 carbon atoms, 2-cyanethyl group or 2,2 2-rich-orethyl to give the N-carboxy-aminomethylphosphonic acid derivative of the general formula IV, in which R represents a methyl or ethyl group and - R 1 represents an alkyl group having 1 to 3 carbon atoms, 2-cyanethyl or 2,2,2-trichloroethyl, which is then hydrolyzed in aqueous medium, in the presence of hydrochloric acid or hydrobromic acid, under reflux, to the desired aminomethylphosphonic acid.

The process for the preparation of the aminomethylphosphonic acid according to the invention differs from the processes previously known in an advantageous manner in that the two reaction steps, namely the reaction of the hexahydrol, 3,5-triazine-N, N ', N'-triscarboxylic acid ester of formula II with phosphorous acid ester of formula (III), and the following - hydrolysis of the resulting N-carboxy-aminomethylphosphonic acid derivative of formula (IV), under reaction conditions that can be easily maintained, practically quantitative yield of the respective products. Because then - - in addition, hexahydrol ester, 3,5-triazine-N, N ', N'⁴The tri-carboxylic acids of the formula (II) required as starting material can be obtained in a simple manner in virtually quantitative yield by reaction of the corresponding urethane with form 229945 aldehyde, the process of the invention being particularly suitable for the economical production of aminomethylphosphonic acid on an industrial scale.

The invention is illustrated by the following non-limiting examples.

Example 1

Preparation of O, O-diethyl N-ethoxycarbonyl-aminomethylphosphonate

To a mixture of 20.22 g (0.066 mol) of ethyl hexahydro-1,3,5-triazine-N, N, N'-tris-carboxylic acid and 28.4 ml (0.22 mol) of diethyl phosphite at an internal temperature of 125 ° C was stirred with 2 ml of boron trifluoride etherate with stirring. The temperature of the reaction mixture is then raised to 150^CAfter stirring for 1 hour at 150 ° C, an additional 2 ml of boron trifluoride etherate is added, the temperature temporarily dropping to 105 ° C and then gradually rising back to 150 ° C. The reaction mixture was stirred at 150 ° C for 1 h, after which time the volatiles were distilled off under high vacuum. 48.0 g (100% of theory) of O, O-diethyl N-ethoxycarbonylaminomethylphosphonate are obtained, which product can be used directly for subsequent hydrolysis without further purification. The product has a boiling point of 130⁰Celsius / 20 Pa.

Example 2

Preparation of aminomethylphosphonic acid

To 23.9 g (0.1 mol) of O, O-diethyl-N-ethoxycarbnyl-aminomethylphosphonate (crude product from Example 1) was added 100 ml of 20% hydrochloric acid and the mixture was heated under reflux for 20 hours. The hydrochloric acid was then evaporated in vacuo to give 12.6 g of practically pure aminomethylphosphonic acid as a residue. Recrystallization from water / acetone gave 9.4 g (84.7% of theory) of pure aminomethylphosphonic acid, m.p. 277-281 ° C.

Example 3

The following products were obtained in an analogous manner to Example 1 using boron trifluoride etherate as a catalyst:

by reaction of hexahydro-1,3,5-triazine-N, №, N^at-tris-carboxylic acids and diethylphosphite Ο, Ο-diethyl-N-methoxycarbonylaminomethylphosphate, boiling point 130 ° C / 1 Pa;

by reaction of hexahydro-1,3,5-triazine-N, N ', N methyl ester^:-tris-carboxylic acid and dimethylphosphite O, O-dimethyl-N-methoxycarbonylaminomethylphosphonate boiling at 125 ° C / 11 Pa and reacting hexahydro-1,3,5-triazine-N, N ', N'-tris ethyl ester carboxylic acids and dimethyl phosphite O, O-dimethyl-N-ethoxycarbonylaminomethylphosphonate boiling point 130 ^CC / 13 Pa.

Hydrolysis of these products with aqueous hydrochloric acid or aqueous hydrobromic acid affords aminomethylphosphonic acid in 85-90% yield.