DD243493A1 - PROCESS FOR THE PREPARATION OF ALKYL-3-ARYL-3-ACYL-2-METHYL CARABATE - Google Patents

Abstract

The invention relates to a process for the preparation of acyl-3-aryl-3-acyl-2-methylcarbazaten of the formula I, which are used as active ingredients in crop protection agents. The aim of the invention is the development of a simple process for the preparation of the title compounds by N-methylation of alkyl-3-aryl-3-acyl-carbazates of the formula II without the aid of expensive processes for the separation of the starting compounds. The pure N-alkali metal salts of the compounds of formula II are methylated for this purpose with an excess of a methylating agent at temperatures between 50 and 80C, wherein the methylating agent itself serves as a solvent or an inert under the reaction conditions solvent is used. Formulas I and II

Description

HH-CO-OR ³

in which

R, R ¹ , R ² , R ³ and R ^{4 have the} above meanings, characterized in that the compounds of the formula II are first converted into their N-alkali metal salts, the unconverted fraction of the compounds of the formula II is separated off and the pure N- Alkali metal salts of the compounds of formula II with the aid of a 1.2 to 20 times the molar excess of a methylating agent of the formula III

CH ₃ -X (III)

wherein X is a leaving group cleavable under the N-methylation conditions, methylated at temperatures between 40 and 14O ⁰ C, wherein the methylating agent itself serves as a solvent or an inert under the reaction conditions solvent is used.

2. A process for the preparation of alkyl-3-aryl-3-acyl-2-methylcarbazaten of the formula I according to item 1, characterized in that R ^{4 is} a C ₃ ^ cycloalkyl, C ₂ -t alkoxyalkyl, phenyl or benzyl. \

Field of application of the invention

The invention relates to a process for the preparation of novel alkyl-3-aryl-3-acyl-2-methylcarbazates which are prepared by N-methylation of alkyl-3-aryl-3-acyl-carbazates. The compounds can act as active ingredients in crop protection products

 Find use.

Characteristic of the known technical solutions

The synthesis of alkyl-3-aryl-3-acyl-2-alkylcarbazaten by N-alkylation of alkyl-3-aryl-3-acyl-carbazaten is known '

(DE-OS 3139298; DE-OS 3202487).

A disadvantage of the previously proposed syntheses is that the remaining after nichtquantitativer implementation in the reaction mixture alkyl-3-aryl-3-acyl-carbazate must be removed from this, since they can act in some cases antagonistic.

The removal of the alkyl-3-aryl-3-acyl-carbazate by known methods, such as. As distillation or solvent extraction, possible, but in some cases difficulties, since the physicochemical parameters of both

Only slightly differentiate between classes of compounds.

Methods for purifying the title compounds by preparative column chromatography are also known, however, the yield losses and the limited substance throughput rate which are present have a limiting effect on the use of these

Procedure off.

In the known method is also a disadvantage that the N-alkylation of the alkyl-3-aryl-3-acyl-carbazate is carried out at relatively high reaction temperatures, so that due to the thermal load, a partial decomposition of

Title links can not always be ruled out.

The aim of the invention is the development of a simple process for the preparation of novel alkyl-3-aryl-3-acyl-2-methylcarbazaten by N-methylation of alkyl-S-aryl-S-acyl-carbazaten without the help of laborious / experienced Separation of the starting compounds.

Explanation of the essence of the invention

The object of the invention is to avoid the presence of an alkyl-3-aryl-3-acyl-carbazate in the reaction product caused by non-quantitative conversion and to save labor-intensive processes for the separation of the starting compounds

The object is achieved in that alkyl-3-aryl-3-acyl-2-methylcarbazate of the formula I _t

η which

λ, R ¹ and R ² independently represent hydrogen, halogen or a C ₁ ^ un / branched alkyl, and 3 ^{3 is} a C ^ un / branched alkyl, and

= t ^{4 is} a C ₁ ^, alkyl, C ₂ -4 alkenyl, C ₃ ^ cycloalkyl, C 2-4 alkoxyalkyl, C 3-6 alkoxyalkoxyalkyl, C ₂ ^ alkylcarbonyl, C ₃ ^

Alkyicarbonylalkoxy, C ₂ ^ alkylthioalkyl, an optionally substituted phenyl, 2-furyl, 5-lsoxazolyl or aralkyl, are prepared by reacting alkyl-3-aryl-3-acyl-carbazate of the formula II,

W \

in which

R, R ¹ , R ² , R ³ and R ^{4 have the} above meaning,

first converted into their N-alkali metal salts, the unconverted portion of the compounds of formula II separated and the pure N-alkali metal salts of the compounds of formula II with the aid of an excess of a methylating agent of the formula II

CH ₃ -X, (III)

wherein X is a leaving group cleavable under the N-methylation conditions, methylated at temperatures between 40 and 140 ° C, wherein the methylating agent itself serves as a solvent or an inert under the reaction conditions solvent is used.

Suitable methylating agents are e.g. the corresponding methyl halides, especially methyl iodide, methyl esters of sulfonic acids, e.g. Methanesulfonic acid ester (mesylate) or dimethyl sulfate.

The compound of formula II is first converted to a salt, e.g. B. an N-alkali metal salt, in particular a Na or K salt, which by reaction of the corresponding compound of formula II with a strong base, for. Example, an alkali metal hydride, amide or alcoholate, is obtained in a solvent inert under the reaction conditions. Such salts are conveniently prepared by heating, preferably under reflux conditions.

The synthesis of contaminated alkyl-3-aryl-3-acyl-2-methylcarbazate not starting compounds is now achieved in an advantageous manner when the proportion of non-salt form of the compounds of formula II is first removed from the reaction mixture.

The non-salted compounds of formula II can be directly removed with the solvent after completion of salt formation (e.g., by rapid aspiration or filtration, decantation, centrifugation). But it is also possible to first remove the solvent used from the reaction mixture and extract the non-salt form of the compound of formula II with an inert under the conditions, not salt-dissolving solvent from the mixture.

The N-methylation is carried out by adding to a N-alkali metal salt of the compound of formula II a methylating agent, such. As methyl iodide, admits.

The methylating agent is used in excess of from 1.2 to 20 mol, preferably from 1.5 to 10 mol, based on the N-alkali metal salt.

The methylating agent may expediently serve as solvent at the same time. However, it is also possible to disperse the salt of a compound of the formula II in a solvent which is inert under the reaction conditions and then to add the methylating agent. The N-methylation is conveniently carried out with heating, for. B. a temperature of 40 to

The proposed method for N-methylation of the alkali metal salts of the compounds of formula II has the advantage over the known prior art that the compounds of formula I are obtained in very high yields and high purity. A further advantage of the process according to the invention is that it is possible to work at lower reaction temperatures than in known processes, whereby the thermal load is reduced and partial decomposition of the title compounds is avoided

 The following examples illustrate the process according to the invention in more detail:

example 1 Preparation of new alkyl-S-aryl-S-acyl-methylcarbazates

A) Ethyl S-f S -dichlorophenyl-S-benzoyl-methylcarbazate (Compound 16)

1. Synthesis by known methods

7.05 g (0.02 mol) of ethyl 3- (3,4-dichlorophenyl) -3-benzoylcarbazate were dissolved in 60 ml of anhydrous THF and added at room temperature to a suspension of 0.96 g (0.04 mol) of NaH in 40 ml dropped freshly purified THF.

The mixture was then stirred under exclusion of moisture for 1 hour at room temperature and 4 hours at 80 ⁰ C, with a gelatinous precipitate formed. The suspension was cooled to room temperature, slowly added dropwise with stirring 5.68 g (0.04 mol) of methyl iodide and then stirred at 80 ° C for 20 hours. 100 ml of diethyl ether and then cautiously 70 ml of water were added to the cooled THF suspension, stirred thoroughly and the organic phase was separated off. The aqueous phase was extracted three times with 50 ml of methylene chloride, the combined organic phases and dried with MgSO ₄ . The solvent was removed in vacuo and the remaining brown oil was added to a silica gel column (eluant gasoline / ethyl acetate 1: 1). This gave 5.0 g (68.5% of theory) of the desired product in the form of a pale yellow amorphous residue.

¹ H NMR spectrum in CDCl ₃ / TMS

/ ppm / M

CH ₂ -CH ₃ 1.24 Triplett N-CH ₃ 3.20 singlet CH ₂ -CH ₃ 4.19 quadruplet Ar-H • 6.98; 7.45 Triplett 7.98 doublet CIAR-H 7.15; 7.36 doublet 7.30 singlet

2. Synthesis according to the proposed method

A reaction mixture as described under A) 1. was stirred for 1 hour at room temperature and for 4 hours at 80 ° C and the suspension was cooled to room temperature. The THF was carefully decanted from the precipitate, the precipitate was stirred twice with 30 ml of anhydrous THF and the majority of the solvent removed by decantation. The remainder of the solvent was removed in vacuo, the remaining residue at room temperature with 14.2 g (0.1 mol) of methyl iodide and then the reaction mixture was kept at 60 ° C for 12 hours. The cooled residue was taken up in 100 ml of methylene chloride, the sodium iodide separated and the solvent and methyl iodide removed in vacuo.

There were obtained 6.7 g (91% of theory) of the product in the form of a yellow oil, which solidified in the refrigerator to a pale yellow amorphous residue.

IR and 'H-NMR spectrum were identical to those of the product of variant A) 1st

B) Isopropyl S-O-chloro-methylphenoxy-S-benzoyl-methylcarbazate (Compound 20)

1. Synthesis according to known method

6.95 g (0.02 mol) of isopropyl SO-chloro-methyl-phenyl-S-benzoyl-carbazate in 80 mL anhydrous toluene were added dropwise at room temperature to a suspension of 0.5 g (0.021 mol) NaH in 40 mL absolute toluene. The mixture was then stirred for 1 hour at room temperature and 4 hours at 80 ⁰ C with exclusion of moisture. The suspension was cooled to 40 ⁰ C and slowly added dropwise with stirring 2.6 g (0.022 mol) of freshly distilled dimethyl sulfate. It was then further stirred for 12 hours with exclusion of moisture at 60 ° C and then the reaction mixture was cooled to room temperature.

The reaction was stopped after adding 20 ml of water. The reaction solution was stirred well, the organic phase separated and dried over MgSO ₄ .

The solvent was removed in vacuo and the remaining brown oil was added to a silica gel column (eluant gasoline / ethyl acetate 1: 1).

Thus, 4.9 g (68% of theory) of the title compound were obtained in the form of a yellow syrupy residue.

2. Synthesis according to the proposed method

A reaction mixture as described under B) 1 was stirred for 1 hour at room temperature and for 4 hours at 80 ^° C. and the suspension was cooled to room temperature. The toluene was carefully decanted from the precipitate formed. The precipitate was stirred well twice with 30 ml of anhydrous toluene, the solvent was decanted off and the remaining Na-salt of the isopropyl-Sp-chloro-methylphenyD-S-benzoyl-carbazate remaining in the flask was mixed with 60 ml of anhydrous toluene, 7.6 g (0.06 mol) of dimethyl sulfate was added dropwise at room temperature and stirred for a further 12 hours with exclusion of moisture at 60 ⁰ C. The solution was cooled to room temperature, mixed with 20 ml of water, stirred well, the organic phase separated and dried over MgSO ₄ . After removal of the solvent and the excess dimethyl sulfate, 6.4 g (88% of theory) of the title compound were obtained in the form of a dark yellow oil, which solidified in the refrigerator to a yellow syrupy residue.

Example 2

Following the procedures described in Example 1 A) 2 nd and B) 2, the novel compounds listed in Table 1 were prepared. The elemental analysis values of all compounds agreed with the calculated values within the error limits.

Table 1: Physico-chemical constants of the synthesized alkyl-3-aryl-3-acyl-2-methylcarbazate of the formula I.

(D

/ R CC R ¹ -R R ² • R ³ R ⁴ Fp / Kp IR * / cm " ¹ / i / erb. R / ⁰ C / vCO-0 vCO-N Mr. -H -H -CH ₃ -CH ₂ OCH ₃ Kp ₂ 158-9 1720 1690 1 (known) -H -H -H -CH ₃ -CH ₂ C ₆ H ₅ Kp ₁ 182 1720 1690 2 -H -H 6-CH ₃ -CH ₃ -CH ₂ OCH ₃ Kp ₁ 155-6 1725 1690 3 (known) 2-CH ₃ 'Fp 69-71 -H 6-CH ₃ -CH ₃ -CH ₂ OC ₂ H ₅ Kp ₁ 168-70 1725 1695 4 2-CH ₃ -H 6-CH ₃ -CH ₃ -C ₆ H ₅ Kp _2r5 195-7 1725 1670 5 2-CH ₃ Mp 96-8 -H 6-CH ₃ -CH ₃ -C ₃ H ₅ Ic) Kp ₂ , ₅ 181-4 1725 1680 6 2-CH ₃ Mp 83-5 -H -H -CH ₃ -CH ₂ OC ₂ H ₅ Kp ₂ 194-8 1720 1695 7 3-CI -H -H -CH ₃ -CH ₂ CgHs Mp 130 1720 1695 8th 3-CI -H -H -CH ₃ -C ₃ H ₅ Ic) pale yellow oil 1720 1690 9 3-CI -H 5-CI -CH ₃ -CH ₂ OCH ₃ pale yellow oil 1725 1695 10 2-CH ₃ -H 5-CI -CH ₃ -C ₃ H ₅ (C) pale yellow oil 1725 1685 11 2-CH ₃ -H -H -CH ₃ -C ₆ H ₅ pale yellow syrup 1720 1675 12 3-CI -H -H -C ₂ H ₅ -C ₂ H ₅ pale yellow oil 1710 1670 13 3-CI -H -H -C ₃ H ₇ Ii) -Cghs pale yellow syrup 1720 1670 14 3-CI -Cl -H -CH ₃ -G ₆ H ₆ light yellow 1720 1678 15 3-CI. crystalline. amorphous -Cl -H ^ -C ₂ H ₅ -C ₆ H ₅ light yellow 1 725 , 1683 16 ^a 3-CI crystalline. amorphous -Cl -H -C ₃ H ₇ Ii) -C ₆ H ₅ yellow krist. amorphous 1720 1685 17 3-CI -CH ₃ -H -CH ₃ -C ₆ H ₅ light yellow 1718 1670 18 3-CI crystalline. amorphous -CH ₃ -H -C ₂ H ₅ -C ₆ H ₅ pale yellow oil 1720 1670 19 3-CI -CH ₃ -H -C ₃ H ₇ Ii) -CgH ₅ gelberSirup " 1715 1675 20 ^a 3-CI -F -H -CH ₃ -C ₆ H ₅ yellow krist: amorphous 1723 1 675 21 3-CI -F -H -C ₂ H ₅ -C ₆ H ₅ yellow oil 1725 1685 22 3-CI -F -H -C ₃ H ₇ Ii) -C ₆ H ₅ gelberSirup 1715 1683 23 3-CI

* = only the C = O corresponding absorptions are given '= the preparation of the compounds is described in Example 1

Example 3

Following the procedure described in Example 1 A) 1 and A) for the synthesis of alkyl-S-aryl-S-acyl ^ -methylcarbazaten of formula I were in the same experimental procedure, the same batch size, reaction time and 5-fold molar excess of methyl iodide the compared with the results obtained by the known and the proposed method.

Table 2: Yielding methylation of alkyl 3-aryl-3-acyl-carbazates by known (1) and proposed (2) methods

Yield /% / No. (1) (2) _

82.5 86 69 82 72.5 92.5 71 93 68.5 91 65 89

Claims (1)

Invention claim: 1. A process for the preparation of alkyl-S-aryl-S-Äcyl ^ -methylcarbazaten of the formula I. ₃
\ N-CO-OR " ψ \ r in which R, R ¹ and R ² independently of one another represent hydrogen, halogen or a C ₁ -j-branched alkyl, and R ^{3 is} a C ₁ ^ ₄ un / branched alkyl, and R ⁴ is a C ₁ ^ alkyl, C ₂ -4 alkenyl, _C3 ^ cycloalkyl, C ₂ ^ alkoxyalkyl, C ₃ ^. Alkoxyalkoxyalkyl, C. _{2-4Alkylthioalkyl,} an optionally substituted phenyl, 2-furyl, 5-isoxazolyl or aralkyl,
by methylation of alkyl-S-aryl-S-acyl-carbazates of the formula II