GB2098210A

GB2098210A - Process for the halogenation of N-(O,O'-dialkylphenyl)alaninates and homologues thereof

Info

Publication number: GB2098210A
Application number: GB8213005A
Authority: GB
Original assignee: Rhone Poulenc Agrochimie SA
Current assignee: Bayer CropScience SA
Priority date: 1981-05-08
Filing date: 1982-05-05
Publication date: 1982-11-17
Also published as: FR2505327B1; IT8221070A0; BE893117A; FR2505327A1; IT1152114B; LU84129A1; DE3217029A1; NL8201764A

Abstract

A process is described for the meta-halogenation of N-(o,o'-dialkylphenyl)alaninates and homologues thereof by reaction with a halogen in the presence of a Lewis acid, to produce compounds of the general formula:- <IMAGE> wherein R<1> and R<5>, which may be the same or different, each represent an alkyl group, R2 represents a halogen atom, R<3> represents a hydrogen atom or methyl radical and R<4> represents an alkyl group. At least 2 moles of Lewis acid per mol of alaninate is required.

Description

SPECIFICATION Process for the halogenation of N-(O,O'-dialkylphenyl)alaninates and homologues thereof The present invention relates to a new process for the preparation of N-(metahalogenophenyl)a laninates and homologues thereof.

Certain N-(metahalogenophenyl)alaninates and their homologues are intermediates which are useful in the manufacture of numerous pesticides, in particular those described in British Patent Specifications Serial Nos. 1,500581 and 2,040289.

They are products of the general formula:

wherein R' and R5, which may be the same or different, each represent an alkyl group (preferably having 1 to 4 carbon atoms), R2 represents a halogen atom, in particular bromine or chlorine, and preferably chlorine, R3 represents a hydrogen atom or a methyl radical and R4 represents an alkyl group (preferably having 1 to 4 carbon atoms).

Hitherto, it has been known to prepare anilino-alkanecarboxylic acid esters from previously substituted anilines (J. Org. Chem. 30, page 4101 (1965); Tetrahedron, 1967, pages 487-498). In the case of the preparation of compounds of general formula (I), and more generally of N-(o,o'-dialkyl-m-halogenophenyl)-alaninates, this requires that o,o'-dialkyl-m-haloge- noanilines are used as starting reactants.

An object of the invention is to avoid the need to use such reactants.

Another object of the invention, derived from the first, is, therefore, to provide a convenient process for the metahalogenation of N-substituted o,o'-dialkylated-aniline derivatives.

The metchalogenation of N-substituted o,d-dialkylated aniline derivatives has already been described (Synthesis, 1971, page 467). In this process, which gives good yields, the reaction is carried out in the presence of acetic acid, but this process is not satisfactory in the case of starting materials of the general formula:

(wherein R', R5, R3, and R4 are as hereinbefore defined) as it has been found with them that only parahalogenated products are obtained.

An object of the invention is therefore to provide a suitable process for the metahalogenation of alaninates of general formula (II).

It has now been found that the aforementioned objects can be achieved by virtue of a process which forms the subject of the present invention and which comprises reacting a halogen with a compound of general formula (II) (wherein R', R5, R3, and R4 are as hereinbefore defined) in the presence of at least 2 mols of a Lewis acid per mol of compound of the formula (II).

The molQOr ratio Lewis acid/compound of general formula (II) is generally between 2.5 and 4, preferably between 3 and 3.5.

The halogen which is used is preferably a halogen in the molecular form, preferably chlorine or bromine.

AICI3, Al Br3, BF3, SnCI4 and TiCI3 may be mentioned as Lewis acids which can be used.

The process of the invention is particularly applicable to the compound of general formula (I) wherein R', R5, R3 and R4 each represent a methyl radical and R2 represents a chlorine atom.

The reaction is generally carried out in the presence of an inert solvent, i.e. a solvent which does not undergo chemical reaction with the reactants or reaction products under the operating conditions.

Suitable solvents which may be mentioned are polyhalogenated aliphatic hydrocarbons which are liquid at the reaction temperature used, in particular 1,2-dichloroethane and carbon tetrachloride.

The temperature of the reaction mixture is generally between - 1 0 C and the boiling point of the solvent, preferably between 1 5 and 40"C. It is particularly convenient to carry out the reaction at ambient temperature.

The concentration of compounds of formulae (I) and (II), taken together, is generally between 0.2 and 5 mols/litre, preferably between 0.5 and 3 mols/litre.

It must be clearly understood that the present account does not indicate the nature of the reaction mechanism and is restricted to a description of the means used; in particular, the process of the invention comprises a reaction with the aid of three substances (reactants), i.e.

the compound of general formula (II), the halogen and the Lewis acid, it being clearly understood that prior reactions of a more or less determined nature can be involved. Thus, the Lewis acid can add onto the compound of general formula (II) before the halogen reacts; it is clear that this particular course of the reaction operations or phenomena falls within the general scope which has been described for the process of the invention.

Pesticides can be obtained from the products of general formula (I) by any known means, in particular by reaction with acid chlorides carrying appropriate functional groups. These techniques are described, in particular,in British Patent Specifications Serial Nos. 1 500581 and 2040289.

The following non-limitative Examples illustrate the invention and show how it can be put into practice.

EXAMPLE I Methyl N-(2,6-dimethylphenyl)alaninate (414 g) is added dropwise, with stirring of the reaction medium, to a suspension of AIC1s(801 g) in 1,2-dichloroethane (1.6 litres). The reaction medium is cooled with the aid of a bath of iced water so as to keep it at 20"C. After the addition has ended, the stirring is continued, the temperature being kept at 20"C. Chlorine gas (142 g) is then injected into the medium at a rate of 2 g/minute. The reaction medium is cooled so as to keep it at 25"C. After the reaction has ended, the stirring is continued for 1/2 hour, and the reaction mixture is then hydrolysed by pouring it slowly onto crushed ice (3 kg), with stirring.The liquid is decanted and the organic phase is separated off and washed with N aqueous hydrochloric acid (2 x 0.3 litre) and then with water (2 X 0.3 litre).

The washed organic phase is evaporated so as to remove the solvent. An oil (417 g, yield: 86%) is obtained which consists of the product of the formula

The product [methyl N-(3-chloro-2-, 6-dimethylphenyl)alaninate] can be purified by distillation at 1 0O"C under an absolute pressure of 0.5 mm Hg (= 0.66 millibar). The product purified in this way is a crystalline product melting at 43.5 C.

EXAMPLE 2 Example 1 is repeated, the starting alaninate being replaced by the same molar amount of methyl N-(2, 6-d iethylphenyl)alan i nate.

Methyl N-(3-chlorn-2,6-diethylphenyl)alaninate is obtained with a yield of 64%. Its refractive index at 20"C for the sodium D line (n2g) is equal to 1.528. Its boiling point under an absolute pressure of 0.4 mm Hg (= 0.53 millibar) is 11 5 C.

EXAMPLE 3 Example 1 is repeated, but the alaninate is replaced by the same molar amount of methyl N (2, 6-diisopropylphenyl)alaninate. Methyl N-(3-chloro-2,6-diisopropylphenyl)alaninate is obtained with a yield of 33% in the form of an oil having a refractive index (n20) equal to 1.521. Its boiling point under an absolute pressure of 1 mm Hg (=1,3 millibars) is 130-135"C.

Claims

1. A process for the preparation of a compound of the general formula:

(wherein R1 and R5, which may be the same or different, each represent an alkyl group , R2 represents a halogen atom, R3 represents a hydrogen atom or a methyl radical and R4 represents an alkyl group) which comprises reacting a halogen with a compound of the general formula:

(wherein R', R5, R3 and R4 are as hereinbefore defined), in the presence of at least 2 mols of a Lewis acid per mol of the compound of general formula (II).

2. A process according to claim 1 for the preparation of a compound of general formula (I) depicted in claim 1 wherein R1, R5 and R4, which may be the same or different, each represent an alkyl group containing from 1 to 4 carbon atoms, R2 represents a chlorine or bromine atom and R3 is as hereinbefore defined, which comprises reacting chlorine or bromine with a compound of general formula (II) depicted in claim 1, wherein R1, R5 and R4, which may be the same or different, each represent an alkyl group containing from 1 to 4 carbon atoms and R3 is as hereinbefore defined.

3. A process according to claim 1 for the preparation of a compound of general formula (I) depicted in claim 1 wherein R', R5, and R4, which may be the same or different, each represent an alkyl group containing 1 to 4 carbon atoms, R2 represents a chlorine atom and R3 is as hereinbefore defined, which comprises reacting chlorine with a compound of general formula (II) depicted in claim 1, wherein R', R5 and R4, which may be the same or different, each represent an alkyl group containing from 1 to 4 carbon atoms and R3 is as hereinbefore defined.

4. A process according to claim 1 for the preparation of the compound of general formula (I) depicted in claim 1 wherein R', R5, R3 and R4 each represent a methyl radical and R2 represents a chlorine atom, which comprises reacting chlorine with the compound of general formula (II) depicted in claim 1, wherein R1, R5, R3 and R4 each represent a methyl radical.

5. A process according to claim 1 wherein the halogen used is in the molecular form.

6. A process according to claim 2 wherein the chlorine or bromine used is in the molecular form.

7. A process according to claim 3 or 4 wherein the chlorine used is in the molecular form.

8. A process according to any one of claims 1 to 7 wherein the Lewis acid is used is chosen from the group consisting of AICI3, Al Br3, SnCI4 and TiCI4.

9. A process according to claim 8 wherein the Lewis acid used is AICI3.

10. A process according to any one of claims 1 to 9 wherein the reaction is carried out in an inert solvent.

11. A process according to claim 10 wherein the inert solvent is a liquid polyhalogenated hydrocarbon.

1 2. A process according to claim 10 wherein the inert solvent is 1,2-dichlorethane or carbon tetrachloride.

1 3. A process according to any one of claims 1, 2 and 5 to 1 2 for the preparation of a compound of general formula (I) depicted in claim 1 wherein R', R5 and R4, which may be the same or different, each represent an alkyl group containing from 1 to 4 carbon atoms, R2 represents a chlorine or bromine atom and R3 is as hereinbefore defined, which comprises reacting chlorine or bromine in the molecular form with a compound of general formula (II) depicted in claim 1, wherein R', R5 and R4, which may be the same or different, each represent an alkyl group containing from 1 to 4 carbon atoms and R3 is as hereinbefore defined, in the presence of an inert solvent.

1 4. Process according to any one of claims 1 to 1 3 for the preparation of the compound of general formula (I) depicted in claim 1, wherein R', R5, R3 and R4 each represent a methyl radical and R2 represents a chlorine atom, which comprises reacting chlorine in the molecular form with the compound of general formula (II) depicted in claim 1, wherein R', R5, R3 and R4 each represent a methyl radical, in the presence of an inert solvent.

1 5. A process according to any one of claims 1 to 14 wherein the reaction is carried out at a temperature between - 1 0'C and the boiling point of the solvent.

1 6. A process according to any one of claims 1 to 1 5 wherein the reaction temperature is between 1 5 and 40to.

1 7. A process according to any one of claims 1 to 1 6 wherein the concentration of compounds of the formulae (I) and (II), taken together, is between 0.2 and 5 mols/litre.

1 8. A process according to any one of claims 1 to 1 7 wherein the concentration of compounds of the formulae (I) and (II), taken together, is between 0.5 and 3 mols/litre.

1 9. A process according to any one of claims 1 to 1 8 wherein the molar ratio Lewis acid/compound of the formula (II) is between 2.5 and 4.

20. A process according to any one of claims 1 to 1 9 wherin the molar ratio Lewis acid/compound of the formula (II) is between 3 and 3.5.

21. A process according to claims 1 to 20 substantially as hereinbefore described with special reference to Examples 1, 2 or 3.

22. Compounds of general formula (I) depicted in claim 1, wherein R' and R5, which may be the same or different, each represent an alkyl group, R2 represents a halogen atom, R4 represents an alkyl group and R3 is as hereinbefore defined, when prepared by a process claimed in any one of claims 1 to 21.

23. Compounds according to claim 22 wherein R'. R5 and R4, which may be the same or different, each represent an alkyl group containing from 1 to 4 carbon atoms, R2 represents a chlorine or bromine atom and R3 is as hereinbefore defined.

24. Compounds according to claim 22 or 23 wherein R1, R5 and R4, which may be the same or different, each represent an alkyl group containing from 1 to 4 carbon atoms, R2 represents a chlorine atom and R3 is as hereinbefore defined.

25. Methyl N-(3-chloro-2,6-dimethylphenyl)alaninate when prepared by a process claimed in any one of claims 1 to 21.

26. Methyl N-(3-chloro-2,6-diethylphenyl)alaninate and methyl N-(3-chloro-2, 6-diisopropylhenyl)alaninate when prepared by a process claimed in any one of claims 1 to 21.