EP1131284A1

EP1131284A1 - Method and intermediate products for producing bis(oxim)monoethers

Info

Publication number: EP1131284A1
Application number: EP99972621A
Authority: EP
Inventors: Wassilios Grammenos; Hubert Sauter; Andreas Gypser; Herbert Bayer; Norbert Götz; Roland Götz
Original assignee: BASF SE
Current assignee: BASF SE
Priority date: 1998-11-20
Filing date: 1999-11-12
Publication date: 2001-09-12
Also published as: AU1383100A; CN1326437A; WO2000031024A1; US6344589B1; BR9915500A; HUP0104064A2; JP2002530366A; HUP0104064A3

Abstract

The invention relates to a method for producing bis(oxim)monoethers of formula (I), wherein the substituents have the following meaning: R<1> is an unsubstituted C1-C4-alkyl or a methyl substituted by C2-C4-alkenyl, C2-C4-alkinyl or phenyl; R<2>, R<4> mean, independently of each other, hydrogen or methyl and R<3>, R<5> mean, independently of each other, hydrogen or C1-C4-alkyl, trifluoromethyl or phenyl; and to intermediate products that can be obtained with this method.

Description

Processes and intermediates for the production of bis (oxime) monoethers

description

The present invention relates to a process for the preparation of bis (oxime) monoethers of the formula I,

in which the substituents have the following meaning:

R ¹ unsubstituted C ₁ -C ₄ alkyl or methyl substituted by C ₂ -C ₄ alkenyl, C ₂ -C ₄ alkynyl or phenyl;

R ² , R ⁴ independently of one another are hydrogen or methyl;

R ³ , R ⁵ independently of one another hydrogen or -CC ₄ alkyl, trifluoromethyl or phenyl.

In addition, the invention relates to monooximes of the formula III and obtainable with this process

Mono (oxime ether) of the formula IV

Bis (oxime) monoethers of the formula I and mono (oxime ethers) of the formula IV are interesting intermediates for the preparation of the fungicidal crop protection active compounds known from WO-A 95/21153, WO-A 95/21154 and WO-A 97/03057. N (OCH ₃ ) -COOCH ₃

IV

The structure of the alkenylalkyl-substituted dione derivatives I and IV is not described in the prior art (cf. WO-A 95/21153, WO-A 95/21154, WO-A 96/16030 and WO-A 97/03057 ). The general schemes in these documents only show synthetic routes that start from α-diketones a) or the corresponding bis-oximes b) (see Scheme 1).

Scheme 1:

Due to the bifunctionality, a) in the oximation of the α-diketones or b) in the alkylation of the α-bisoximes, mixtures of substances are to be expected. In addition to the desired monocondensation / substitution product, the unreacted and the double-reacted product are generally also found in such reactions. In the present case, however, there is still a more serious problem. The alkenylalkyl radical (corresponds in Scheme 1: R ') is sterically much more demanding than the methyl radical (R''). A monocondensation / substitution product would probably be formed with the wrong regio- and stereochemistry (cf. Liebigs Ann. Chem. (1974) 1908-1914). The sequence shown in Scheme 1 is therefore out of the question for the synthesis of bis (oxime) monoethers of the formula I.

The object of the present invention was therefore to find a process by means of which compounds of the formula I and IV can be built up in a targeted manner.

We have found that this object is achieved by the fact that

a) an acetoacetic ester of the formula II,

treated with a nitrite first under alkaline conditions and then in acid and

b) the monoxime III obtained in this way

in the presence of a base to the mono (oxime ether) IV

alkylated and finally

c) reacting mono (oxime ether) IV with hydroxylamine or its acid addition salt to give bis (oxime) monoether I. O 00/31024

The process according to the invention is illustrated by the example of the synthesis of hex-5-en-2, 3-dione-3 - (O-methyloxime) 2-oxime (see Scheme 2).

Scheme 2

The individual stages of the method according to the invention are explained in more detail below.

Stage a):

Stage a) is analogous to that described in US 4,707,484

Procedure executed.

Alcohols such as methanol and, in particular, water can be used as solvents. Under certain circumstances, it can be helpful to add solubilizers such as surfactants or ethylene glycol.

Suitable bases are in particular sodium and potassium hydroxide, which are generally used in an equimolar amount or in an up to 10-fold molar excess based on the acetoacetic ester II. Nitrite is understood to mean, for example, an alkali metal nitrite, in particular sodium nitrite, which is generally used in an aquimolar amount or in an excess of up to 30 mol%, based on the acetoacetic ester II.

The reaction temperature should generally not exceed 40 ° C, otherwise undesirable side reactions occur. It is therefore preferred to work in water at -20 to 40 ° C., in particular at 0 to 15 ° C.

The reaction mixture usually clears up after a period of 10 to 48 hours. Now a pH of 0 to 5 and preferably 1 to 3 is set with an acid such as hydrochloric acid or sulfuric acid.

The processing takes place according to common methods, for example by extraction. For cleaning, the oxime can be converted into the corresponding salt with bases, for example, and then precipitated again with acid.

The acetoacetic ester II used for the reaction can be prepared as described in Tetrahedron (1985) 4633 (see Scheme 3).

Scheme 3:

A II

The alkenylalkyls of the formula A, where R ² to R ^{5 have} the meaning given in claim 1 and L ^{1 represents} halogen, acyloxy, alkylsulfonyloxy or arylsulfonyloxy, are known or can be synthesized by processes known from the literature (Z. Org. Khim. (1997) 486; Bull. Chem. Soc. Jpn. (1980) 2586; J. Am. Chem. Soc. (1984) 2211; J. Am. Chem. Soc. (1960) 1886; DE-A 19 556 66 ; DE-A 33 173 56; EP-A 271212; Tetrahedron Let. (1986) 6027; Tetrahedron Let. (1994) 1371 and 2679; J. Fluorine Chem. (1997) 67; Helv. Chim. Acta (1951) 1514 ; Organomet. Chem. (1985) 395). O 00/31024 level eb):

The alkylation is usually carried out in the presence of an inert organic solvent. Among others, aliphatic or aromatic hydrocarbons such as toluene, xylene, heptane or cyclohexane, aliphatic or cyclic ethers such as 1, 2-dimethoxyethane, tetrahydrofuran or dioxane can be used. Polar aprotic solvents are preferably used: ketones such as acetone, nitriles such as acetonitrile, amides such as dimethylformamide, dimethylacetamide or N-methylpyrrolidone or ureas such as tetramethylurea.

A halide, preferably a chloride or bromide, a sulfate, preferably dimethyl sulfate, a sulfonate, preferably a methanesulfonate (mesylate) or a toluenesulfonate (tosylate) is usually used as the alkylating agent.

The amount of base or alkylating agent, based on compound III, is preferably between one to two times the equimolar amount.

As a rule, in the presence of an inorganic base such as sodium or potassium hydroxide, sodium or potassium carbonate, sodium or potassium hydrogen carbonate or an alkali metal alcoholate such as sodium methoxide or potassium tert. -butanolate worked.

The reaction temperature is generally between 0 ° C and 50 ° C - preferably between 0 ° C and 40 ° C and especially at room temperature.

The processing can take place, for example, by an extractive route.

To remove residual amounts of alkylating agent, it can be advantageous to wash the reaction mixture with, for example, ammoniacal solution.

Stage c):

Hydroxylamine is used either in the form of an acid addition salt or as a free base, the latter being able to be released from the salt by adding a strong base.

The acid addition salts of hydroxylamine are preferably used. All common acids are suitable for the production of the acid addition salts. The following are just a few examples: carboxylic acids such as acetic or propionic acid, dicarboxylic acids such as oxalic or succinic acid, mineral acids ren such as phosphoric or carbonic acid and especially hydrochloric acid or sulfuric acid.

If the acid addition salts of hydroxylamine are used, it is generally advantageous to add a base in order to bind the acid released during the reaction. In many cases a pH of 3 to 7 and in particular 4 to 6 has proven to be advantageous for the oximation. Outside of these pH ranges, side reactions such as ring closure reactions can occur.

As a rule, 1 to 2.5 molar equivalents of a base are added. In particular, pyridines, trialkylamines, sodium hydroxide, sodium acetate and sodium methylate are suitable as bases. When using sodium acetate, glacial acetic acid is usually added.

Conversely, of course, the hydroxylamine can also be used as the free base and one of the acids mentioned can be used to adjust the above-mentioned pH range.

Examples of solvents which can be used are those described in the previous step. In addition, carboxylic acids such as acetic acid or water / pyridine mixtures are also suitable. Alcohols such as methanol, ethanol, n-propanol or i-propanol and mixtures of these with water and / or pyridine are particularly suitable.

The reaction temperature is usually -20 to 100 ° C and preferably 0 to 40 ° C and in particular 20 to 25 ° C.

The reaction mixture is preferably worked up, as described in the previous step, by means of extractive methods. To remove the base completely, it may be helpful to wash the crude product beforehand with a dilute aqueous acid and then with water.

With the method according to the invention, in particular monooximes of the formula III,

Mono (oxime ether) of the formula IV and

Bis (oxime) monoethers of the formula I,

produce in which the substituents have the following meaning:

R ¹ is unsubstituted Cι-C ₄ alkyl or by C ₂ -C ₄ alkenyl, C ₂ -C ₄ -alkynyl or phenyl-substituted methyl;

R ² , R ⁴ independently of one another are hydrogen or methyl;

R ³ , R ⁵ independently of one another hydrogen or Cχ-C ₄ alkyl, trifluoromethyl or phenyl.

As illustrated by the compounds I in Scheme 4, the above formulas can also be expressed in a different, more conforming notation.

Scheme 4: possible spellings of compounds I

In the definitions of the compounds I, II, III, IV and A given above, collective terms were used for the radicals R ¹ to R ⁵ , which stand for individual lists of the individual group members. The alkyl, alkenyl or alkynyl radicals can be straight-chain or branched. Furthermore, for example:

Halogen: fluorine, chlorine, bromine or iodine;

-C 1 -C ₄ alkyl:

Methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl and 1, 1 -dimethylethyl;

C ₂ -C alkenyl: ethenyl, prop-1-en-1-yl, prop-2-en-1-yl, 1-methylethenyl, but-1-en-1-yl, but-2-en-1 -yl, but-3-en-1 -yl, 1-methyl-prop-l-en-l-yl, 2-methyl-prop-1-en-1-yl, 1-methyl-prop-2-ene -l-yl and 2-methyl-prop-2 -en-l-yl;

C ₂ -C alkynyl: ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, l-methyl-2-propynyl;

In view of their suitability as intermediates for the preparation of the crop protection active compounds known from WO-A 95/21153, WO-A 95/21154 and WO-A 97/03057, the compounds of the formulas I, III and IV with the following substituents are particularly preferred, where the preference can be seen individually or in combination:

R ^{1 is} methyl, ethyl, benzyl or propargyl and in particular methyl or ethyl;

R ² , R ⁴ independently of one another are hydrogen or methyl;

R ³ , R ⁵ independently of one another are hydrogen, methyl or trifluoromethyl.

In particular, the compounds listed in the following preparation examples are preferred.

Manufacturing examples

Production of Monooxime III (stage a))

Example 1 5-methyl-hex-5-en-2,3-dione-3-oxime

200 g of 2-acetyl-4-methyl-pent-4-enoic acid methyl ester (preparation: see Tetrahedron (1985) 4633) in 2000 ml of aqueous 10% potassium hydroxide solution were mixed with 85 g of sodium nitrite at 10 ° C. and 18 Stirred at 23 ° C for hours. 1000 ml of 10% strength sulfuric acid were then added dropwise with ice cooling in such a way that the internal temperature remained below 10 ° C. Then you stirred in for as long - 10 ° C after, until the C0 ₂ development was finished. Working up was carried out with methyl tert. -butyl ether extracted, the combined organic phases were extracted with 3 N sodium hydroxide solution and the alkaline phases were brought to pH 1 with 20% sulfuric acid.

5 The mixture was then extracted with methylene chloride, dried over sodium sulfate and the solvent removed in vacuo. 142 g of the title compound remained as a yellow oil which crystallized on standing.

0 ⁱ H-NMR (CDC1 ₃ , ppm): δ = 4.8 (1H); 4.6 (1H); 3.3 (2H); 2.4 (3H); 1.8 (3H).

Preparation of the mono (oxime ether) IV (stage b))

5 Example 2

5-methyl-hex-5-en-2,3-dione-3- (O-methyloxime)

141 g of 5-methyl-hex-5-en-2, 3-dione-3-oxime from Example 1 were dissolved in 750 ml of acetone, and 165.6 g of potassium carbonate were added. Then 145 g of dimethyl sulfate in 100 ml of acetone were added dropwise and the mixture was subsequently stirred at 23 ° C. for 4 hours. The solvent was then removed in vacuo, the residue in methyl tert. -butyl ether / water added and the aqueous phase several times with methyl tert. -butyl ether extracted. The combined organic 5 phases were washed with 15% ammonia solution and water, dried over sodium sulfate and the solvent removed in vacuo. 141 g of the title compound remained as a yellow oil.

^X H NMR (CDCI ₃ , ppm): δ = 4.77 (1H); 4.57 (1H); 4.0 (3H); 3.2 (2H). 0

Example 3

5-methyl-hex-5-en-2,3-dione-3- (O-ethyloxime)

285.7 g of 5-methyl-hex-5-en-2, 3-dione-3-oxime from Example 1 were dissolved in 750 ml of acetone and 335.8 g of potassium carbonate were added. Then 362 g of diethyl sulfate in 300 ml of acetone were added dropwise and the mixture was subsequently stirred at 23 ° C. for 2 hours. The solvent was then removed in vacuo, the residue in methyl tert. -butyl ether / water added and the aqueous phase extracted again with methyl 0-tert-butyl ether. The combined organic phases were washed with 15% ammonia solution and water, dried over sodium sulfate and the solvent removed in vacuo. 355.4 g of the title compound remained as a yellow oil. 5 ⁱ H-NMR (CDCI ₃ , ppm): δ = 4. 8 (1H); 4th 6 (1H); 4th 3 (2H); 3rd 2 (2H); 2nd 4 (3H); 1 . 7 (3H); 1 . 3 (3H).

Preparation of the bis (oxime) monoether I (stage c))

Example 4

5-methyl-hex-5-en-2,3-dione-3- (O-methyloxime) -2-oxime

283.4 g of 5-methyl-hex-5-ene-2, 3-dione-3- (O-methyloxime) in 800 ml of methanol were added dropwise to the solution of 140.6 g of hydroxylammonium chloride in 400 ml of water and 216.7 g of pyridine, and the mixture was stirred for 3 hours at 23 ° C. The solvent was then removed in vacuo and the residue was added to ice water. Then a pH of 1 was set with 20% sulfuric acid, and the precipitated product was filtered off with suction, in methyl ter. -butyl ether added and washed with water. The organic phase was then dried over sodium sulfate and the solvent was removed in vacuo. There remained 266 g of the title compound as a colorless solid.

ⁱ H-NMR (CDC1 ₃ , ppm): δ = 9.3 (1H); 4.8 (1H); 4.6 (1H); 4.0 (3H); 3.3 (2H).

Example 5 5-methyl-hex-5-en-2,3-dione-3- (O-ethyloxime) -2-oxime

211.3 g of hydroxylammonium chloride in 400 ml of water and 240 g of pyridine were reacted with 342.4 g of 5-methyl-hex-5-en-2,3-dione-3- (O-ethyloxime) in 800 ml of methanol as in Example 4. 305 g of the title compound were obtained as a yellowish solid.

¹ H NMR (CDCI ₃ , ppm): δ = 9.4 (1H); 4.8 (1H); 4.6 (1H); 4.2 (2H); 3.3 (2H); 2.1 (3H); 1.8 (3H); 1.3 (3H).

Claims

claims

1. Process for the preparation of bis (oxime) monoethers of the formula I,

in which the substituents have the following meaning:

R, R ⁴ independently of one another are hydrogen or methyl;

R ³ , R ⁵ independently of one another are hydrogen or -CC ₄ alkyl, trifluoromethyl or phenyl,

characterized in that

a) an acetoacetic ester of the formula II,

is treated with a nitrite first under alkaline conditions and then in acid and

b) the monooxime III obtained in this way

in the presence of a base to the mono (oxime ether) IV

alkylated and finally

c) the mono (oxime ether) IV is reacted with hydroxylamine or its acid addition salt to form the bis (oxime) monoether I.

2. The method according to claim 1, characterized in that a pH of 5 to 7 is set in step c).

Mono (oxime ether) of the formula IV,

in which the substituents have the following meaning:

R ¹ is unsubstituted Cι-C ₄ alkyl or substituted C ₂ -C alkenyl, _{C2-C4-alkynyl} or phenyl methyl, -

R ² , R ⁴ independently of one another are hydrogen or methyl;

R ³ , R ⁵ independently of one another are hydrogen or C ₁ -C alkyl, trifluoromethyl or phenyl.

4. monooxime of the formula III,

in which the substituents R ² to R ^{5 have} the meaning given in claim 3.