MXPA98007125A - New processes for the preparation of pesticide intermediaries - Google Patents

Abstract

The present invention relates to: a process for preparing a compound of general formula (I) which is used as an intermediate in the synthesis of compounds pesticidally or as active pesticides.

Description

NEW PROCESSES FOR L? PREPARATION OF PESTICIDE INTERMEDIARIES This invention relates to a process for preparing certain cyanomethylpropane derivatives and to the use of these compounds in the synthesis of pesticides and pesticide intermediates. First, ethyl 2, 3-dicyanopropionate was prepared and characterized by Higson and Thorpe (J. Chem. Soc. 89, 1460 (1906)) who obtained the material in good yields (70-81%) by the cyanohydrin reaction of formaldehyde with the sodium salt of ethyl cyanoacetate. Dickinson. { J. A. Chem. Soc. 82, 6132 (1960)} repeated this work. This method of preparing the dicyanopropionates suffers from a significant disadvantage since it is necessary first to isolate the cyanohydrin from intermediate formaldehyde. This cyanohydrin is highly soluble in water is obtained by prolonged continuous extraction and has a limited stability, after the violent decomposition on the distillation attempt. In addition, this reaction requires care given the risk of dimeric collateral product formation. The preparation of dicyanapropionates has also been described by Whiteley and Marianelli (Synthesis (1978), 392) with the process conducted for 2, 3-disubstituted succinodinitriles.

REF .: 28221 from cyanoacetates, an aldehyde (1 to 3 carbons of alkylaldehydes or benzaldehydes) and potassium cyanide via 3-substituted-dicyclopropionates-2, 3- (which are not isolated). However, the yield increases dramatically from isobutyrylaldehyde to acetaldehydes. In the same manner Smith and Horwitz (J. Am. Chem. Soc. 1949, 71_, 3418) describe the same reaction with a ketone with a yield of 70%. This prior art therefore shows that the yields are improved with an increase in the size of the group adjacent to the carbonyl group. In one aspect of the present invention, it is sought to provide a process for preparing cyanomethyl propane derivatives by satisfying one or more of the following criteria: - avoiding the use of formaldehyde cyanohydrin; avoiding dimerization of the lateral reaction; - directly obtaining the required product in high performance and with high purity. Therefore, the present invention provides a process for preparing a compound of formula (I): wherein R represents a straight or branched chain alkyl having up to 18 carbon atoms; or a salt thereof; which comprises the reaction of a cyanoacetate of formula (II): - R02C-CH2CN II wherein R is as defined above, with a cyanide salt and a formaldehyde or a source thereof. Preferably R represents a straight or branched chain alkyl having from 1 to 6 carbon atoms and more preferably R represents ethyl. Suitable cyanide salts include metal salts and organic salts (e.g., tetraalkylammonium cyanide such as tetrabutylammonium cyanide). Preferably the cyanoacetate of formula (II) is reacted with an alkaline earth metal or alkali metal cyanide salt, with alkali metal cyanide salts being especially convenient for use in the present invention, particularly potassium cyanide or sodium cyanide. The product can conveniently be isolated as the alkaline earth metal or alkali metal salt. Alternatively, the reaction mixture is acidified, for example with a mineral acid such as sulfuric acid or hydrochloric acid, to give the compound of formula (I).

When a compound of formula (I) above is desired (instead of a salt thereof) high yields are generally obtained, when the reaction mixture is acidified with the addition of water. While formaldehyde can be used by itself, the reaction is more convenient for use in the polymerized form known as formaldehyde [(HCOH) n], available for example from Aldrich Chemical Company. The reaction is generally carried out using about 1 molar equivalent of a compound of formula (II); about 0.95 to 1.0 molar equivalents of cyanide salt; and about 1 molar equivalent of the formaldehyde compound (based on the formaldehyde content). The reaction can be carried out in the presence of a solvent. Preferably, the reaction is carried out in a solvent medium which is usually an alcoholic medium or dimethyl-formamide (DMF), methyl N-pyrrolidone (NMP), dioxane, tetrahydrofuran (THF) or dimethoxyethane. Especially preferred solvents are alcohols of 1 to 6 carbon atoms such as methanol or, more preferably, ethanol anhydride. Although the temperature of the reaction is not critical, the reaction will normally be carried out at about 0 to about 120 ° C or at the reflux temperature of the solvent. The best results in general are obtained by the introduction of the formaldehyde source after the other reagents have been combined. The reaction generally takes place under anhydrous conditions (the reaction procedures are understood as forming an equivalent of water), as in the event of prolonged exposure to aqueous conditions, there is a risk that the ester group of the compound of the formula (I) is subjected to hydrolysis (due to the basic conditions reached during the reaction) for the corresponding acid of the formula (I) (in which R is replaced by hydrogen) and subsequently subjected to decarboxylation to give 1,2- dicyanoethane. The compound of formula (I) is employed in the preparation of pesticidally active compounds, for example as described in European Patent Publication Nos. 0295117 and 0234119, and O93 / 06089. In particular, the process of the invention can be part of an in situ preparation of another pesticide intermediary and in a further aspect of the invention provide a process for the preparation of the compound of formula (III): (ip) where Ri is cyano; W is nitrogen or -CR4; R and R4 independently represent halogen; and R3 represents halogen, haloalkyl (preferably trifluoromethyl), haloalkoxy (preferably trifluoromethoxy) or -SF5; wherein, the process comprises: (a) reacting a cyanoacetate of formula (II) as defined above, with a cyanide and formaldehyde salt or a source thereof, to give a compound of formula (I) as defined previously; and (b) reacting the compound of formula (I) further obtained with the diazonium salt of a compound of formula (IV): wherein W, R2 and R3 are as defined above, to give a compound of formula (V) wherein W, R, Ri, R2 and R3 are as defined above, followed by cyclization of said compound of the formula (V). The compounds of formula (V) above possess a chiral center giving increases to different enantiomers, and may also exist as different geometric isomers. All forms are contained by the present invention. In this process, the product of reaction step (a) is generally acidified with an alcoholic solution of a mineral acid, preferably an ethanolic solution of hydrogen chloride. This also facilitates any product of the acid from the step (a). ) of the reaction (lead to the corresponding compound of the formula (I) in which R is replaced by hydrogen) is re-esterified. For these reasons it is also preferred that in this process, step (a) of the reaction take place under substantially anhydrous conditions.

The reaction step (b) is generally carried out in the presence of an inert solvent, for example, water, acetonitrile, dichloromethane or DMF, or more preferably an alcohol solvent (for example methanol or ethanol) and is optionally quenched (for example with sodium acetate). The diazonium salt of a compound of formula (IV) can be prepared using diazotizing agents known in the literature and are conveniently prepared with a molar equivalent of sodium nitrite and a mineral acid (eg, hydrochloric or sulfuric acid), to a Temperature of approximately -10 < ^ C to about 50 °, more preferably from about 0 ° C to about 5 ° C. The diazonium salt of the compound of formula (IV) is generally prepared in situ with solvents such as alcohols tending to rapidly reduce the diazodium salts.

In the present reaction, the reaction of the diazonium salt of the compound of formula (IV) to give a compound of formula (V) above in general occurs faster than the reduction of the diazodium salt.

Subsequent to hydrolysis, preferably using light conditions with a base such as sodium hydroxide, sodium carbonate or amino, it may be necessary to cyclize the compounds of formula (V) to a compound of formula (III). The molar ratio of the compounds of formula (II): (IV) is generally from about 1.5: 1 to about 1: 4, preferably from about 1.3: 1 to about 1: 1, more preferably from about 1. 1: 1 The compounds of formula (II) and (IV) above are described in the literature, for example see EP-Al-0295117. The compounds of formula (V) above are novel and further constitute a further feature of the present invention. The following non-limiting examples illustrate the invention.

Example 1 Preparation of Ethyl 2,3-dicyanopropionate Potassium cyanide (13.0 g, 0.2 M) in absolute ethanol was stirred and ethyl cyanoacetate (22.6 g, 0.2 M) and paraformaldehyde (6.0 g, 0.2 M) were added at room temperature. environment ^. After 5 minutes the white suspension was heated under reflux conditions for 12 minutes, and the orange solution was evaporated to dryness in vacuo below 25 ° C to give a buffered solid. The solid (the potassium salt) was dissolved in water (400 ml), acidified to pH 5 with a solution of hydrochloric acid 2, giving a red oil. The mixture was extracted with dichloromethane and the extracts were dried and evaporated to dryness in vacuo to give the title compound as a red oil (23.5 g), XH NMR (CDCl 3) d 4.3 (2H, q), 3.95 (1H, t), 3.0 (2H, d), 1.35 (3H, t); indéntico with an authentic sample. The distilled material had b.f. 132-136 ° C at 0.5 mmHg. Performance: 77% Comparative example according to J.Chem Soc. 89, 1460 (1906) A solution of sodium ethoxide [prepared from sodium (25.2 g, 1.15 M) and absolute ethanol (650 ml)] was stirred under an inert atmosphere and it was treated with ethyl cyanoacetate (127.7 ml, 1.2 M) over a period of 20 minutes. The solution was cooled to below 10 ° C and then slowly added to a solution of formaldehyde cyanohydrin (freshly prepared, 70g, 0.2M) in absolute ethanol (200ml) at 5 ° C for 55 minutes. After standing overnight, the mixture was poured into ice water (1L) and acidified to pH 1-2 with concentrated hydrochloric acid. This was extracted with dichloromethane, dried under magnesium sulfate anhydride and evaporated to give a dark orange oil (150.6g). This was distilled in vacuo to collect the title compound (73.6g) as a colorless oil, b.f. 144-148 ° / lmbar. Performance. 40% The superiority of the process of the invention is also clearly demonstrated on this prior art.

Example 2 Process for the preparation of 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethyl-phenyl) pyrazole. Sodium cyanide (20 g, 0.408 M) and ethyl cyanoacetate (46 g, 0.480 M) were dissolved in absolute ethanol (300 ml) under an inert atmosphere. Formaldehyde (12.2g, 0.408M) was added, producing an exotherm, and the temperature was kept below 50 ° C. The reaction mixture was then stirred at room temperature between 5 and 7 hours, cooled between 0 and 5 ° C, and an ethanolic solution containing hydrogen chloride (0.45 M) was added maintaining the temperature below 5 ° C. The reaction mixture was left overnight and 111 ml of a solution of hydrochloric acid (0.73M) in ethanol was added to the suspension further obtained at about 5 ° C. 2,6-Dichloro-4-trifluoromethylalaniline (84.44 g, 0.367M) was added at this temperature followed by sodium nitrite (35.84g, 0. 514M) resulted in the formation of ethyl 2, 3-dicyano-2- [2,6-dichloro-4-trifluoromethylphenyl) azo] propionate, which was isolated by column chromatography, eluting with a pentane / ether solution and / or reversible phase chromatography with an acetonitrile-water solution; or by distillation removal, by dissolving the reaction mixture in toluene, washing the toluene solution with water and evaporating the etoluene to dryness. XH NMR (CDC13) 1.37 (t, 3H), 3.55 (s, 2H), 4.43 (c, 2H), 7.65 (s, 2H). Ammonium gas (9.6g, 0.56M) was pumped into the reaction mixture at 0 ° C. The ethanol was evaporated from the reaction mixture under reduced pressure and the concentrated solutions were placed in a mixture of toluene and ethyl acetate. This solution was washed with water and after concentration of the toluene phase at 80 ° C, the solution was cooled to give the title compound as a crystalline solid, and the solutions were then concentrated and cooled to give a second crop. of the recrystallized product, mp 141-142 ° C (combined weight of the title compound 87.54g, yield based on the initial aniline material = 78%).

It is noted that, in relation to this date, the best method known to the applicant to carry out the aforementioned invention. It is the one that is clear from the description of the present invention. Having described the invention as above, the content in the following is refiled as property.

Claims (18)

1. A process for preparing a compound of the formula (I): wherein characterized by straight or branched chain alkyl having from 1 to 18 carbon atoms, or a salt thereof, which is characterized in that it causes reacting a cyanoacetate of formula (II): R02C-CH2CN II where R is as defined above, _-. with a cyanide salt, and formaldehyde or a source thereof.

2. A process according to claim 1, characterized in that the cyanide salt is an alkali metal or alkaline earth metal salt.

3. A process according to claim 2, characterized in that the cyanide salt is potassium or sodium cyanide.

4. A process according to claim 1, 2 or 3, characterized in that R represents a straight or branched chain alkyl having from 1 to 6 carbon atoms.

5. A process according to any of claims 1 to 4, characterized in that the compound of formula (II) is ethyl cyanoacetate.

6. A process according to any one of claims 1 to 5, characterized in that the formaldehyde source is paraformaldehyde.

7. A process according to any one of claims 1 to 6, characterized in that the reaction is carried out in the presence of a solvent which is an alcoholic medium.

8. A process according to any one of the preceding claims, characterized in that the reaction is carried out at a temperature from about 0 ° C to about 120 ° C.

9. A process according to any one of the preceding claims, characterized in that the reaction is carried out using about 1 molar equivalent of the compound of formula (II); about 0.95 to 1.0 molar equivalents of the cyanide salt, and about 1 molar equivalent of the formaldehyde compound.

10. A process according to any one of the preceding claims, characterized in that the reaction mixture is acidified after the reaction of the cyanoacetate of formula (II) with the cyanide and formaldehyde salt.

11. A comformity process with any one of the preceding claims, characterized in that the reaction is carried out under substantially anhydrous conditions.

12. A process for the preparation of a compound of formula (III): III wherein c -------- c * - r - za - b because R is cyano: W is nitrogen or -CR 4. R2 and R4 independently represent halogen; and R3 represents halogen, haloalkyl; haloalkoxy or SF5; t which process is characterized because it comprises: (a) reacting a cyanoacetate of formula d i: R02C-CH2N II wherein R represents a straight or branched chain alkyl having from 1 to 18 carbon atoms, with a cyanide and formaldehyde salt or a source thereof, to give a compound of formula (I) as defined in claim 1; Y (b) reacting a compound of formula (I) further obtained with the diazonium salt of a compound of formula (IV): (IV) wherein W, R2 and R3 are as defined above; to give a compound of formula (IV): (V) wherein W, R, Rx, R2 and R3 are as defined above, followed by cyclization of said compound of formula (V).

13. A process according to claim 12, characterized in that the product of step (a) of the reaction is treated with an alcoholic solution of an acid, preferably a mineral acid.

14. A process according to claim 12 or 13, characterized in that the molar ratio of the compounds of formula (II): (IV) is from about 1.5: 1 to about 1: 4, preferably from about 1.3: 1 to about 1: 1.

15. A process according to claim 12, 13 or 14, characterized in that step (a) of the reaction is carried out under substantially anhydrous conditions.

16. A process according to any one of claims 12 to 15 in which the cyclization is carried out by the hydrolysis of the compound of formula (V).

17. A compound of formula (V): characterized in that Ri is cyano; W is nitrogen or -CR4; R2 and R4 independently represents halogen; and R3 represents halogen, haloalkyl, haloalkoxy or SF5.

18. A 2, 3-dicyano-2- [(2,6-dichloro-4-trifluoromethylphenyl) azo] propionate compound.