JPS6156188A - Lactic acid silyl ester - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing lactic acid silyl esters and their use for the synthesis of compounds with herbicidal activity.

It is already known that 2-tosyloxypropionic acid (silyl-methyl)-ester can be used as an intermediate for the synthesis of compounds with herbicidal activity (see European Published Patent Application No. 0.096.554, DE). Published Patent No. 3.519.289 and European Published Patent No. 0.
No. 095,115) 112-) 2-tosyloxypropionic acid (silyl-methyl)- when siloxypropionic acid halide is reacted with a hydroxymethylsilyl derivative.
It is also disclosed that esters are obtained. However, it is a disadvantage of this process that the compounds required as starting materials have to be prepared in each case in a two-step reaction. Based on the starting materials used:
2-Tosyloxypropionic acid (silyl-methyl)-nisterha can only be obtained in relatively low yields for practical purposes.

Lactic acid of the present formula is added to chloromethyl of the formula % ( ) in which R represents alkyl or aryl in the presence of a tertiary amine and if appropriate in the presence of further diluents. A new process has been discovered for the preparation of lactic acid silyl esters of the formula %, where R has the meaning given above, by reaction with silane at temperatures of 50 to 120°C.

Furthermore, it has been discovered that the lactic acid silyl esters of formula (1) according to the invention are of great importance as intermediates for the synthesis of compounds with herbicidal activity.

It must be mentioned very particularly that the lactic acid silyl esters of formula (1) can be prepared in excellent purity and in very high yields by the process according to the invention. In particular, it would not have been expected based on known techniques that the reaction would not occur with hydroxy groups, but with a high selectivity of Cal with xy groups.

The method according to the invention has many advantages. That is, the reaction components are available in large quantities and can be handled without problems on an industrial scale. The operating costs required to carry out the process are also low and do not present any disadvantages in the treatment of the reaction mixture obtained after the reaction.Furthermore, only a simple acid binder is required and the use of Only a diluent is essential.Nevertheless, in particular the lactic acid silyl esters of the formula (D) can be prepared by the process according to the invention not only in very high yields but also without undesired side reactions. Furthermore, if lactic acid silyl ester of the formula (υ) is produced by the method of the present invention, 2-)siloxy-propionic acid (silyl-methyl)-ester, which is important as an intermediate for herbicide synthesis, can be obtained. The products can be produced in a simpler way than by known methods.

When using the S enantiomer of lactic acid and chloromethyl-trimethyl-silane as starting materials and using N,N-dimethyl-cyclohexylamine as the tertiary amine, the reaction process according to the invention is illustrated by the following formula: can be: * (S) In the above formula and in the description below, the asymmetrically substituted carbon atom in each case is marked with an (*) when an optically active compound is involved. The symbol "S" or rRJ indicates the absolute configuration at an asymmetrically substituted carbon atom.

Formula (II) provides a clear definition of the lactic acid required as starting material in the process of the invention. Racemic lactic acid as well as optically active lactic acid can be used here.

Particular preference is given to using the S enantiomer of lactic acid.

Racemic lactic acid, as well as two optically active forms of lactic acid, are known.

Formula (III) provides a definition of the chloromethylsilane required as starting material in the process of the invention. In this formula, R preferably represents alkyl having 1 to 4 or 12 carbon atoms or phenyl.

The following compounds may be mentioned as examples of chloromethylsilanes of formula (In 2 ).

Chlormethyl-trimethylsilane, Chlormethyl-trimethyl-ethyl-silane, Chlormethyl-dimethyl-n-globysilane, Chlormethyl-
trimethyl-n-butyl-silane, chloromethyl-dimethyl-n-dodecyl-silane, chloromethyl-dimethyl-
Phenyl-silane.

The chloromethylsilanes of formula (1) are synthones known in organic chemistry.

All customary aliphatic, aromatic and heterocyclic tertiary amines can be used as bases which act as acid binders in the process according to the invention.

These are preferably triethylamine, tri-n-butylamine, benzyl-dimethylamine, N,N-trimethyl-cyclohexylamine, methyl-dicyclohexylamine, vilison, α-picoline, β-picoline,
r-picoline, methyl-dibensolamine, 1.5-
diazabicyclo[4,5,03non-5-ene and 1.
Contains 8-diazabicyclo[5,4,O]taun-7-ene. N,N-dimethylcyclohexylamine is particularly preferred.

′ All common inert organic solvents,
It can be used in the method of the invention. Suitable are aromatic hydrocarbons such as toluene and xylene, furthermore ketones such as acetone and methyl-isobutyl-ketone, and also nitriles such as acetonitrile. However, if the silyl compound is used in sufficient excess, it is also possible to carry out the reaction in the absence of further organic solvents.

The reaction peat can be varied within certain limits in the process of the invention. Generally the reaction is carried out at a temperature of 60-110°C.

The process of the invention is generally carried out at atmospheric pressure. However, it is also possible to carry out the reaction under elevated or reduced pressure.

When carrying out the process of the invention, 1 mol of lactic acid of the formula CI generally 1 to 4 mol, preferably [1.5 to 5 mol of the formula (
III) chloromethylsilane and preferably 1 to S mol [1,1 to 21 mol of tertiary amine are used. Generally, for the reaction, formula (II) and (
II') by adding a tertiary amine to the mixture of reaction components. However, it is also possible to combine the components in another order.The reaction mixture is then heated to the desired temperature in each case for 10 to 15 hours. The subsequent processing is carried out in the usual manner. Generally, the reaction mixture is cooled, added to dilute aqueous acid, then the phases are separated,
The organic phase is washed several times with water and then subjected to rectification under reduced pressure. The chloromethylsilane used in excess is then recovered in pure form and can be used for further reactions. The lactic acid silyl esters which can be prepared by the process of the invention are obtained in the form of colorless substances and generally do not require auxiliary purification.

If optically active lactic acid is used as a starting material in carrying out the method of the present invention, an optically active lactic acid silyl ester can be obtained. The configuration at the asymmetrically substituted carbon atoms is maintained during the reaction process. Therefore, when the S enantiomer of lactic acid is used, the corresponding S enantiomer of lactic acid silyl ester is produced.

The lactic acid silyl ester of formula (1) is new. Preferred are compounds of formula (1) in which R represents alkyl having 1 to 4 or 12 carbon atoms or phenyl. Particularly preferred is the S enantiomer of the lactic acid silyl ester of the formula: in which R has the meanings already mentioned as preferred for this radical.

It is a useful intermediate for synthesizing a compound having herbicidal properties from the lactic acid silyl ester of formula (1). i.e. phenoxy of the formula: [wherein R has the meaning given above, R1 represents chlorine or trifluoromethyl, R2 represents hydrogen or chlorine and X represents nitrogen, a CH- group or a CCl- group] Zolopionic acid derivatives have the formula CH.

[In the formula, Rh has the above meaning]

The lactic acid silyl ester of 0 to 0 to
2-tosyloxyglobionic acid (silyl-methyl)-2-tosyloxyglobionic acid (silyl-methyl)- is reacted at a temperature of 20° C. and obtained in the second step:
The ester is prepared by reacting the ester with a phenol derivative of the formula in the presence of an acid binder and in the presence of a diluent at 50-120°C lit. be able to.

For example, S of lactic acid (trimethylsilyl)-methyl ester
When the enantiomer and tosyl chloride are used as starting materials and 4-(5,5-dichlorobyrituru-2-oxy)-phenol as the total reaction component, the process of the above method is exemplified by the formula % formula % I can do it.

The phenol derivative 16 of the formula (Vl) which is required as a reaction component when carrying out the above-mentioned process for the preparation of the phenoxyglobionic acid derivative of the formula (F/) is known (see, German Patent Publication No. 2.546゜2
51-@).

Potassium carbonate and sodium carbonate can preferably be used as acid binders in the second step of the above process.

The camellia hydrangeal medium can preferably be used as a diluent in the second stage of the above-described process.

Particularly preferred are ketones such as acetone and methyl isobutyl ketone, as well as acetonitrile and dimethylformamide.

Reaction basin #Lh can be varied within certain limits in the second stage of the process described above. Generally 50-120℃ for reaction,
Preferably it is carried out at a temperature of 60 to 100°C.

In the above-mentioned process 11 for the preparation of phenoxyzolopionic acid derivatives of formula (IV), in the first step as well as in the second step,
It is generally carried out under normal pressure. However, it is also possible to carry out this under elevated or reduced pressure.

When carrying out the second step of the above-described method for producing phenoxyzolobion &i4 conductors of formula (IV), the formula (
per mole of phenol derivative in equivalents or in slight excess of 2-tosyloxyglobionic acid (silylmethyl)-ester of the formula (■) and 1.5 to 2.5 equivalents of acid binder and, if appropriate, anhydrous of calcium sulfate is used. In each case, the reaction components are stirred in the solvent for several hours at the required temperature. The work-up is then carried out in the usual manner, generally by filtering the reaction mixture with suction and concentrating it to remove the residue. The residue is dissolved in an organic solvent and the organic phase obtained is washed successively with dilute aqueous alkali metal hydroxide solution and water, then dried and concentrated.The residue obtained is freed from the volatile components still present. , heating under high vacuum for a short period of time (“incipient distillation”)
When it is desired to produce the R enantiomer of the phenoxypropionic acid derivative of formula 1 (■) purified by It is necessary to use the S enantiomer of the lactic acid silyl ester of formula (1) because Walden inversion occurs at the carbon atom that is Similarly,
The R enantiomer of the lactic acid silyl ester of the formula (1) must in each case be used to synthesize the S enantiomer of the phenoxypropionic acid derivative of the formula (■).

The following example illustrates the process of the invention and the preparation of a phenoxypropionic acid visiting conductor of formula (IV) starting from the lactic acid silyl ester of formula (1) of the invention.

Example 1 *(S) S monoisomer of lactic acid 1a9F (combined α5 mol), 1,8-diazabicyclo[5,4,03-undec-7-nin 7a
A mixture of 9F and methyl-isobutylketone 500-
C1 chloromethylsilane 61, 25? (05 mol)
was added with stirring at a temperature of 80-90°C. The reaction mixture was stirred for a further 16 hours at 80-90°C, then it was cooled and washed with water. The organic phase was separated, dried and concentrated under reduced pressure, and from the remaining residue the remaining volatile components were removed by heating briefly to 50 °C (bath temperature) under a pressure of 20 mbar, and then Distilled. 522 of the product (boiling point 80-82 DEG C. 715 mbar) was obtained. It consisted of 94% of the S enantiomer of 2-hydroxy-propionic acid (trimethylsilyl)-methyl ester. From this a yield of 55% of theory could be calculated.

Example 2 *(S) N,N-trimethylcyclohexylamine 4002 (515 mol) was added to a mixture of the S enantiomer of lactic acid 270F (5 mol) and chloromethylsilane 756fC (6 mol) at room temperature without external cooling. The reaction mixture was added dropwise within 1 hour while stirring and heated to 95°C.
This temperature was maintained for =21-12 hours. The reaction mixture was then cooled in room r=4 and poured into 1.21 g of 10% aqueous sulfuric acid. The organic layer was separated, washed twice with 500 g of water each time, and subjected to rectification under reduced pressure. As a result, 450 ml of distillate from the aqueous phase and 4152 ml (2,58 mol) of chloromethyl-trimethylsilane were collected as a first fraction (boiling point = 50°C/20 mbar).
I got it. The S enantiomer 3719 (2,10 mol) of 2-hydroxyglobionic acid (trimethylsilyl)-methyl ester with a purity of 995% was then obtained in a second distillation at a boiling point of 40 DEG C. and 101 mbar. Based on the reacted chloromethyl-trimethyl-silane, this yields a theoretical amount of 851
% yield could be calculated.

Example 5 CH.

S enantiomer of lactic acid 9.8F (0.1 mol) and chloromethyl-dimethyl-n-propylsilane 50f, N,
12.72 of N-methyl-cyclohexylamine was added dropwise at room temperature with stirring.
The mixture was heated to 0.degree. C., then cooled to room temperature 1, and 50.degree. In this way, the S enantiomer 11.7F of 2-hydroxypropionic acid (tumethyl-n-zorobylsilyl)-methyl ester with a purity of 90% (542% of theory) was obtained. Boiling point 105~b Le.

Example 4 2-[4-(5゜5-dichloropyridyl-2-oxy)
-phenoxy]-globionic acid (trimethylsilyl)-
Preparation of the R enantiomer of the methyl ester.To a solution of tosyl chloride 916F (4.8 mol) in pyridine 8002, 2-
7 oar (4 mol) of the S enantiomer of hydroxypropio/1()IJ methylsilyl)-methyl ester were added at 0<0>C and the reaction mixture was then stirred for an additional 25 hours at D~5<0>C.

Subsequently, 100 F of water is added, the reaction mixture is stirred for a further 2 hours at 5-10°C, and 1600 F of water and 2 F of toluene are added.
After addition of 000F and separation of the phases, an organic phase is obtained, which is divided into 1
After washing twice with 0% aqueous sulfuric acid (total amount 60,002) and then twice with water (15,000F), an oil of 1240F remained after distilling off the toluene. This consists of 96 thi (corresponding to 56 moles) of the S enantiomer of 2-tosyloxypropionic acid (trimethylsilyl) methyl ester, which is the S enantiomer of 2-hydroxypropionic acid (trimethylsilyl) methyl ester used as a starting material. Based on the handedness, the achieved yield was calculated to be 90% of theory. Based on the fact that the reaction product contained 1% of the R enantiomer of the compound of formula (IV), the S/R ratio could be calculated to be 99=1.

(IV-1) 4-(5,5-dichloropyridyl-2-oxy)-phenol 9!5OP (A45 mol), 2-)siloxyglobionic acid (trimethylsilyl)-methyl ester (contains:
! l::S enantiomer 99%, R enantiomer 1%) 1115f(
A suspension of A24 mol) and potassium carbonate 9252 in acetonitrile 5100f was heated under reflux for 15 hours.

After cooling to room temperature, the reaction mixture was filtered. The acetonitrile was then distilled off from the filtrate. The liquid raw material product thus obtained was mixed with toluene 5500? diluted with 5% sodium hydroxide solution, total volume 1500F.
and once with 1% sulfuric acid at 1000F and once with water at 500F. After distilling off toluene, the formula (
IV-1) 2-(4-(5,5-dichloropyridyl-
R enantiomer of 2-oxy)-phenoxycuunoropionic acid (trimethylsilyl)-methyl ester 857% (2,
81 mol) and S enantiomer Z5% of the compound of formula (■-1)
1560W of light oil consisting of R/S comparison? 2:8
The yield was 86.8% of theory based on the S enantiomer of 2-tosyloxypropionic acid (trimethylsilyl)-methyl ester used as the starting material.

Control Example: Production of the R enantiomer of 2-C4-(s,s-dichlorbyrithu-2-oxy)-phenoxycouzolopionic acid (trimethylsilyl)-methyl ester by a known method: (H!-1) 2- (4-(5,5-dichlorbylitrue-2-oxy)
-phenoxy]-gropion 1La2F (α025 mol) in 50 rnl of acetone was added with 1,8-soazabicyclo[5,4,0]-undec-7-nin 4.9
05 mol) was added with stirring at 20°C. The reaction mixture was stirred for a further 60 minutes at room temperature and then 3.7 F (0.05 mol) of chloromethyl-trimethylsilane was added likewise at room temperature. The reaction mixture was heated under reflux for 25 minutes.
time and then again 1,8-soazabicyclo[5,
4,0]-Undec-7-ene α5f and chloromethyl-trimethylsilane α82 were added and this was refluxed again for a further 25 hours, followed by cooling the reaction mixture and evaporating the solvent under reduced pressure. The remaining residue was dissolved in methylene chloride, the organic phase obtained was washed successively with aqueous sodium hydroxide solution, dilute aqueous brine and water, and after drying the organic phase was concentrated. From the remaining residue, under a pressure of 2 mbar,
By heating to 80℃ (bath water) for a short period of time,
Remove the remainder of the starting component and prepare 2-[4-(5゜5-
The R enantiomer 2.5 f (the theoretical amount of 24.2) of dichloropyridyl-2-oxy]-phenoxy]-zolopionic acid (trimethylsilyl) methyl ester is 10.

(IM bath solution in chloroform; cell length 10hi)

Claims (1)

[Scope of Claims] 1. Lactic acid of the formula ▲ (including mathematical formulas, chemical formulas, tables, etc.) ▼ (II) is prepared by the formula ▲ , chemical formulas, tables, etc. ▼ (III) There are formulas ▲ mathematical formulas, chemical formulas, tables, etc. that are reacted with chloromethylsilane [in the formula, R represents alkyl or aryl] at a temperature of 50 to 120°C ▼ ( I) [In the formula, R has the above-mentioned meaning] A method for producing lactic acid silyl ester. 2. The method according to claim 1, which uses the S-enantiomer of lactic acid as a starting material. 3. The method according to claim 1, wherein the starting material is chloromethylsilane of formula (III) in which R represents alkyl having 1 to 4 or 12 carbon atoms or phenyl. The method according to claim 1, wherein 4,N,N-dimethylcyclohexylamine is used as the tertiary amine. 5. The method according to claim 1, wherein the reaction is carried out at a temperature of 60 to 110°C. 6. 1 to 4 mol of formula (III) per 1 mol of lactic acid of formula (II)
2. The method of claim 1, using 1 to 3 moles of chloromethylsilane and 1 to 3 moles of a tertiary amine. 7. Lactic acid silyl ester of formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I) [In the formula, R represents alkyl or aryl]. 8. The lactic acid silyl ester according to claim 7, wherein in formula (I), R represents an alkyl having 1 to 4 or 12 carbon atoms or phenyl. 9. Lactic acid silyl ester according to claim 7 of the formula ▲ Numerical formula, chemical formula, table, etc. ▼. 10. Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (IV) [In the formula, R has the above meaning, R^1 represents chlorine or trifluoromethyl, R^2
represents hydrogen or chlorine; has the meaning given above] with tosyl chloride in the presence of an acid binder and if appropriate in the presence of a further diluent.
The reaction was carried out at a temperature of 20 °C, and the formula obtained in the second step ▲ is a mathematical formula, a chemical formula, a table, etc. ▼ (V) [wherein R has the above meaning and Tos represents tosyl] 2-tosyloxy-propionic acid (silyl-methyl)-
The ester in the presence of an acid binder and in the presence of a diluent has the formula ▲ Mathematical formula, chemical formula, table, etc. ▼ (VI) [wherein R^1, R^2 and X have the above-mentioned meanings] ] A method for producing the phenoxypropionic acid derivative, which comprises reacting the phenoxypropionic acid derivative with the phenol derivative at a temperature of 50 to 120°C.