NZ225920A - Aminomethylphosphonate intermediate compounds - Google Patents

Description

New Zealand Paient Spedficaiion for Paient Number £25920 m r^ 1-- NO DRAWINGS 22 5 9 2 0 Priority Date(s): .2^?. r. 7? ;2>&.).....

Complete Specification Filed: Class: .S< • • A m • lO - I publice,ionDa,er!;;;;2;);.t!Ec.,»; P.O. Journal, No: I :,... i Under the provisions of Regulation 23 (1) the .«xgp)s&. — Specification has been ante-dated to 19 JtA- Initials Patents Form No: 5 >- ^ £ ^ ./<? * DIVISIONAL APPLICATION OUT OF NZ PATENT APPLICATION / 0 N0; 209010 24AUG 1988 NEW ZEALAND ^ £ [ vj PATENTS ACT 1953 - Js* COMPLETE SPECIFICATION "INTERMEDIATES USEFUL IN THE PREPARATION OF HERBICIDAL COMPOUNDS" We, RHONE-POULENC AGROCHIMIE, a French body corporate of 14-20 Rue Pierre Baizet, Lyon 9e, France, 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: •/ • j The present invention relates to intermediate products for the preparation of new herbicides belonging to the chemical family of sulphonimides containing an aminomethylphosphonic group, and to processes for preparing m the intermediates.

'TMs specificatioir is a divisional of NZ patent specification No. 209,010 in which new sulphonimide herbicides containing an aminomethylphosphonic group, their preparation and their use are described and claimed.

Numerous intermediate products for the preparation of.herbicides containing an aminomethyl-phospbonic group are known, particularly in European Patents 81,459, 97,522, 55,695, British Patents 1,436,843,. 1,436,844 and 1,449,875 and US patents! 3,835,000 and 4,422,982.

Nevertheless, it is always desirable to extend the range of the intermediates which make it possible to obtain herbicides, in order to have new synthetic routes avail able.

The invention provides intermediates products 2 0 useful in processes described in our N.Z. patent specification No. ;209v010 providing access to herbicides containing an aminomethylphosphonic group, and in a new process for preparing herbicides employing relatively simple reactants, particularly glycine and its derivatives.

These intermediates are a selected group and have the 3 properties that substituent R is readily removable by hydrogenolysis as opposed to, for example, hydrolysis. The intermediates have the advantage of ease of preparation using the process of this invention and of ready conversion to desired sulphonimide herbicides containing the aminomethylphosphonic group.

Z m< 225920 n p The invention provides intermediate products of the formula: OR1 R3 1 I 6 0 = P - CH. - N - CH0 - CO - 0 - R° I 2 2 OR 12 12 in which R and R are such that OR and OR are 1 2 hydrolysable groups; R and R may be in particular an aryl or cycloalkyl or, preferably, alkyl radical, optionally substituted; suitable substituents are halogen atoms and phenyl and cyano groups, and alkyl, alkoxy and alkylcarboxylate groups in which the alkyl groups and moieties preferably contain from 1 to 4 carbon atoms; R* 2 and R generally each contain from 1 to 12 carbon atoms and preferably from 1 to 8 (most preferably 1 to 4) carbon 3 3 $ atoms; R represents a hydrogenolysable group: R may be a 4 5 radical of the formula Ar(R )(R )C- in which Ar is an 4 5 aromatic group, preferably phenyl, and R and R each represent a hydrogen atom, an Ar group or an alkyl group preferably containing at most 6 carbon atoms; and R6 is as 1 2 hereinbefore defined for R and R .

In the various preceding formulae, Ar denotes an 20 aromatic group, preferably aryl and more especially phenyl; this radical Ar may, if desired, carry one or more substituents which are not detrimental to the reactions involved in the process (for example alkyl, alkoxy, nitro ... <1 D ' and halogen, the number of carbon atoms in alkyl and alkoxy substituents being preferably at most 6). 3 Suitable radicals R include benzyl, 1-phenylethyl, 1-phenylpropyl, naphthylmethyl, 5 l-naphthylethyl,l-naphthylpropyl, diphenylmethyl, and trityl (i.e. triphenylmethyl) radicals: benzyl is preferred.

According to a feature of the present invention 1 2 6 compounds of formula (I) in which R , R , R and R are as 3-0 hereinbefore defined are prepared by the reaction of a phosphite (or phosphonic ester) of the formula: 0 - R 1 0 = P - H I 0 - R' (II) 1 2 in which R and R are as hereinbefore defined with formaldehyde and an N-substituted derivative of glycine of 15 the formula R^-NH-C^-CO-O-R**, R3 and R^ being as hereinbefore defined.

The reaction is generally carried out between 0 and 100°C, preferably between 20 and 90°C, by mixing the reactants. Although a large excess (3/1 to 1/3 in molar 20 ratios) of one of the reactants relative to another is possible, in practice it is more advantageous to approach stoichiometry as closely as possible and not to depart by more than 20 mole % from this stoichiometry. It is indeed ,.T Vw/ ^ 225920 one of the major advantages of the invention not to require an excess of one of the reactants relative to the others. Another advantage of the invention lies in the good yields which are obtained in the preparation of the compounds of 5 formula (I) .

Formaldehyde is employed in any of its accessible forms. According to a preferred method it is employed in the form of an aqueous solution of a concentration of between 1% w/v and saturation, preferably of 30 to 40% w/v.

The reaction may be carried out in the presence of an inert solvent, but in general such a solvent is unnecessary and it is indeed another advantage of the invention that a solvent is not required for the preparation of the compounds of formula (I) (except for the water in the aqueous solution of formaldehyde, formalin, used according to the preferred method) .

The reaction product is separated by any means known per se.

Compounds of the formula: OR1' R3 I I 6 0 = P - CH, - N - CH, - CO - OR (III) I I 2' OR /} V ^ // % t r-rf j C31.AUG1933 9 1 • 21 1 in which R and R each represent hydrogen or a group R 2 3 6 or R as hereinbefore defined and R and R are as hereinbefore defined may be converted into herbicidal products (which may be known) of the formula: OR1' I 6 0 = P - CH2 - NH - CH2 - CO - 0 - R° (IV) ' 2' OR (in which the various symbols are as hereinbefore defined) 3 by hydrogenolysis of the R group (which is preferably a benzyl group, removed by debenzylation). Advantageously the hydrogenolysis is carried out in an aqueous or 10 alcoholic medium at ambient or elevated temperature, at atmospheric pressure or above. The catalyst employed may 3 be a known hydrogenolysis catalyst for the R radicals in question. As suitable catalysts there may be mentioned palladium, platinum and Raney nickel. The catalyst may be 15 employed with or without an inert carrier. It is also possible to employ the above-mentioned metals, particularly palladium and platinum, in the form of salts, hydroxides, or oxides, which are converted to the corresponding metal by the action of hydrogen. As preferred debenzylation 20 catalyst, use is made of palladium-based catalysts such as palladium on charcoal or palladium on barium sulphate or palladium hydroxide on charcoal. At the end of the reaction the catalyst may be separated by filtration and 225920 the filtrate evaporated; the product of formula (IV) is thus obtained in a substantially pure state. A major advantage of the invention lies in the fact that the reaction time for this debenzylation is relatively short, vrhich makes it possible to employ smaller quantities of catalysts.

When it is desired to prepare non-ester ified forms of known herbicides, such as, e.g., N-phosphonomethylglycine itself, it is possible to hydrolyse completely or partly the product of formula (IV) in a known manner, e.g. by heating with an aqueous solution of an acidic or alkaline agent, particularly a hydroxide or carbonate of an alkali metal or alkaline earth metal, or a strong inorganic or organic acid, such as hydrochloric, sulphuric, phosphoric, perchloric or arylsulphonic acid.

This hydrolysis may also be accompanied by a salt formation (in order to form agriculturally acceptable salts) or a conversion into other herbicidal derivatives.

According to a feature of the invention compounds 12 3 of formula (I) in which R , R and R are as hereinbefore defined and R® is replaced by H, are generally prepared by 12 3 hydrolysis of compounds of formula (I) in which R , R , R and R^ are as hereinbefore defined, to convert the group OR® to a hydroxy, yielding a compound of the formula C5' n ' (p OR I P I .

OR' - CH„ - RJ I N - CH.

- CO - OH (V) 12 3 in which R , R and R are as hereinbefore defined. In practice, this hydrolysis is a saponification which in general employs a molar quantity of an alkaline agent which 5 is substantially equal to the molar quantity of the compound of formula (I).

By the expression "methods known per se" is meant methods heretofore used or described in the chemical 1iterature.

The following Examples illustrate the invention and show how it can be employed.

Examples 1 to 6 illustrate the synthesis and the physical properties of the herbicidal compounds and chemical intermediates according to the invention. The 15 melting points shown correspond generally to a phenomenon of melting with decomposition.

Example 1: An aqueous formaldehyde solution (30% by weight) (1,466 g; 14.66 moles) is poured, with stirring, at ambient 20 temperature, over 1 h 30 min, into a mixture of ethyl N-benzylglycinate (2,830 g; 14.66 moles) and diethyl '* >,V -A |P^ 225920 phosphite [(CjH^O)(0)H] (2,028 g; 14.17 moles). During the pouring the temperature rises up to 41°C. The mixture ^ is heated at 90°C for 1 h 30 min and then cooled.

To extract the reaction product, (7 1) is added, and the mixture is washed with water (3 x 6 1) . The solvent is removed. A light-brown oil (4,647 g) with a /"-v refractive index n of 1.491 is thus obtained. The yield D is 92.4%. The product obtained has the formula: C2H5^ fH2 " C6H5 0 = P - CH. - N - CH„ - C00CoH_ (VI) | i c 13 C2H5° Example 2: The procedure is as in Example 1 but the diethyl phosphite is replaced with dimethyl phosphite (also called ,'-T\ methyl phosphonate) of the formula (CH^O) ^9 (O) H.

The product of the formula: ch-0 ch- - c,hc 31 \ o = p - ch0 - n - ch- - c00cohc (vii) j 2 2 2 5 ch3o is obtained in 87% yield; its refractive index n is d 1.499.

Example 3: An aqueous solution containing 5% by weight of 3 1AUG;>o8 ( 225920 n /-T\ ( ' : sodium hydroxide (6.8 1) is poured at 40°C, over 1 1/2 h, into the compound of formula (VI) (2,915 g) . The mixture is then heated at 80°C for 1 1/2 h, cooled and washed with CHjClj (4 1). The aqueous solution is acidified to pH 2 5 with 10 N hydrochloric acid (800 ml). The product separates from the aqueous layer in the form of an oil which is extracted with CH2C12 (5 1). The methylene chloride solution is washed with water (2 x 2.5 1). It is evaporated to dryness to yield a product of the formula: C2H5"° f2-C6H5 0 = P - CH. - N - CH- - COOH (VIII) I 1 1 C2H5~° (2,012 g; 75% yield), which crystallises on storage (m.p.: 37°C).

Example 4: The procedure is as in Example 3, the product of 15 formula (VII) being employed in place of the compound of formula (VI) as starting material. The product of formula: 3 1 AUG.'933:. ch,0 3i ?H2 " C6H5 0 = P - CH 2 N - CH 2 COOH (IX) ch3o which melts at 73.8°C is thus obtained in 36% yield.

Example 5: A solution of the compound of formula (VI) (68.6 g) in methanol (150 ml) is charged into a 500 ml reactor. A paste made with water (10 ml) and activated charcoal containing 10% by weight of palladium (9 g) is added. The atmosphere is purged with nitrogen and then hydrogen is circulated for 5 h at 20°C. The material is filtered, the filtrate is evaporated and the product of the formula (C2H50)2 P(O)- CH2 - NH - CH2 - COOC^ (X) (49 g; 97% yield) is thus obtained in the form of a liquid with a refractive index n of 1.451. This compound of formula (X) (12.7 g) is dissolved in an aqueous solution (50 ml) containing 20% by weight of hydrochloric acid. The solution is boiled under reflux for 20 h. It is concentrated under reduced pressure, and the residue washed with methanol. After drying, N-(phosphonomethyl)glycine (6.5 g; 77% yield) is obtained.

Example 6 ; The compound of formula (VIII) (10 g) is dissolved in methanol (50 ml) in a 250 ml reactor. The D 'I AUGJ988

Claims (12)

( ■V259 -12- catalyst paste employed in Example 9 (0.3 g) is added. The atmosphere is purged with nitrogen, and hydrogen is then circulated for 2 h at ambient temperature (20 to 25°C). The material is filtered, the filtrate evaporated and the 5 product of the formula (C2H50)2P(0)-CH2-NH-CH2-C00H (7.5 g: 100% yield) is obtained. After recrystallisation the product melts at 115°C. 3 ? AVGSSS -13- 225920 what we claim is:

1. A compound of the formula 1 3 OR1 R"5 1 ■ 6 0 « P - CH- - N - CH- - CO - 0 - R (I) I 2 OR 12 12 in which R and R are such that OR and OR are hydrolysable 6 groups, R is a hydrogenolysable group and R is 1 2 5 as defined for R and R . 1 2

2. A compound according to claim 1, in which R , R 6 3 and R are alkyl radicals and R is a benzyl radical.

3. Ethyl-N-benzyl-N-diethylphosphonomethyl glycinate. 10

4. Ethyl-N-benzyl-N-dimethylphosphonomethyl glycinate.

5. A process for preparing compounds of the formula: OR1 R3 I 1 6 0 * P - CH0 - N - CH- - CO - 0 - R (I);I 2;OR;-14-;225920;12 3 6;in which R , R , R and R are as defined in claim 1, which comprises the reaction of formaldehyde with a compound of the l 2;formula R -O-P(0)H-OR and a compound of the formula R^-NH-CHj-CO-O-R® in which R1, R^, R3 and R® are as defined in claim 1.;

6. A process according to claim 5 in which the reaction is carried out between 0 and 100°C.;

7. A process for preparing compounds of the formula:;OR1';I 6;0 = P - CH_ - NH - CH_ - CO - 0 - R° (IV);1' 2' 1;in which P. and R each represent hydrogen or a group R or;2 G;R as defined in claim 1 and R is as defined in claim 1, which comprises the hydrogenolysis of a compound of the formula:;OR;0 = P - CH2 - N - CH2 - CO - 0 - R (III);OR;3 1 AUG 1933 ?;225920;-15-;1' 2 • 3;in which R and R are as hereinbefore defined and R and;R® are as defined in claim 1.;

8. A process according to claim 7 followed by the step of hydrolysing the compound obtained to convert the;5 group OR® to a hydroxy group and, optionally, converting the compound thus obtained into a salt thereof.;

9. A process for preparing compounds of the formula:;OR1 R3;I I;0 - P - CH. - N - CH. - CO - OH;I;1 2;OR (V);12 3;in which R , R and R are as defined in claim 1 which;10 comprises the hydrolysis of a compound of the formula I;12 3 6;depicted in claim 5, in which R , R , R and R are as defined in claim 1, to convert the group OR® to hydroxy.;

10. A process according to any one of claims 5 to 9 substantially as hereinbefore described in any one of;15 Examples 1 to 6.;12 3;

11. A compound of the formula I in which R , R , R and R® are as defined in claim 1 when prepared by a process claimed in any one of claims 5, 6 and 10.;3 1 AUG 1988;225920;-16-;

12. A compound of the formula IV depicted in claim 7;1 * 21 6 in which R and R are as defined in claim 7 and R is as defined in claim 1 when prepared by a process claimed in any one of claims 7, 8 and 10. RHONE-POULENC AGROCHIMI By their Attorneys BALDWIN, SON & CAREY