DK151878B - PROCEDURE FOR THE PREPARATION OF A 2-SUBSTITUTED BENZANILIDE - Google Patents

Description

The present invention relates to a process for the preparation of a 2-substituted benzanilide of the general formula:

[III] wherein X represents a halogen atom or a lower alkyl group, and Y represents a hydrogen atom, an alkyl, alkoxy, alkenyloxy, alkynyloxy, benzyloxy or halogenobenzyl oxy group, in which process an o-substituted alkyl benzoate with the general formula:

[I] wherein X is as defined above and R represents an alkyl group is reacted with aniline of the general formula:

[II] wherein Y has the meaning set forth above, in the presence of a C2-4 aryl alcohol of an alkali or alkaline earth metal as catalyst and an organic solvent.

Such a method is known from the Journal of Organic Chemistry, Vol. 28, page 2915 (1963) and U.S. Patent No. 3,462,486. In order for this condensation reaction of an alkyl carboxylate with an aniline to be easily carried out, it is necessary that the alcohol formed as a by-product is removed from the reaction system. Therefore, it has been considered optimal to use an organic solvent which can be azeotropically distilled together with the alcohol formed. For this reason, benzene has been used as an organic solvent. However, it is difficult to prepare the 2-substituted benzanilide in higher yield by this conventional process. In the process, light N-alkylbenzanilide is readily formed as a by-product and it is difficult to completely prevent the formation of this by-product. In addition, the resulting 2-substituted benzanilide is contaminated by the by-product, thereby adversely affecting the 2-substituted benzanilide as a disease control agent.

In addition, from Organic Syntheses, Vol. 26, 1946, page 92, it is further known to react toluidine with phenylsalicylate using 1,2,4-trichlorobenzene as the solvent. However, this process is dependent on the use of a phenol ester as well as the presence of a phenolic OH group in ortho position to the carboxyl group, and in this particular process no alcohol is used as a catalyst.

The object of the present invention is to modify the process set forth at the outset so that the desired product is obtained in a higher yield and the formation of by-products is largely avoided.

This object is achieved with the process according to the invention, characterized in that a mixture of the aniline compound, the C2-4 alcohol of the alkali or alkaline earth metal and a solvent which is not azeotropically distillable with the alcohol formed by the reaction, and of the general formula:

R 1 represents an alkyl group having 1-5 carbon atoms or 2 3 a chlorine atom and R and R represents a hydrogen atom, a chlorine atom or a methyl group, or a solvent of the general formula: R 4 - O - R 5 an n- or iso-butyl or a C5-6 alkyl group, with the exception of toluene, is heated and thereby reacted with the o-substituted alkyl benzoate, in which R represents a C2-4 alkyl group.

The 2-substituted benzanilides prepared according to the invention have a strong germicidal effect and are broad-spectrum effective against the cause of various plant diseases. In particular, they are effective in preventing plant diseases such as pelicularia sukaki, bacterial rice leaf disease, tomato leaf blight, cucumber ski waffle, bean stem advice, altar? naria leaf spot disease on apple trees, apple tablecloth, orange-phoma council, wheat Mbund "(wheat designation), wheat rust, barley gravel, greenhouse rust, coffee rust, rust on ornamental plants, vegetables, cereals and grasses as well as fire, Rhizoctonia soil and Fusarium. they act as disinfectants for seeds and seeds.

The 2-substituted alkyl benzoates are compounds of the general formula [I] wherein X represents a halogen atom such as chlorine, bromine or iodine, or a lower alkyl group such as methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, iso-butyl or tert-butyl, and R represents a C 2-4 alkyl group such as ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl or tert-butyl.

When benzoate is used in which R is a methyl group, N-methylbenzanilide is formed as a by-product. With benzoates in which the residue R is an alkyl group having more than 5 carbon atoms or a phenyl group, the yield of 2-substituted benzanilide is relatively poor.

The aniline used has the general formula [II] wherein Y represents a hydrogen atom or an alkyl group such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, isopentyl, sec -pentyl, tert-pentyl, or an alkoxy group such as a methoxy-, ethoxy-, n-propoxy-.

iso-propoxy, n-butoxy, sec-butoxy, iso-butoxy, tert-butoxy, pentyloxy, iso-pentyloxy, hexyloxy, octyloxy or dodecyloxy group, or an alkenyloxy group such as a vinyloxy, allyloxy or 1-methylallyloxy group, or an alkynyloxy group such as an acetyleneoxy, propargyloxy or 1-propylpropargyloxy group, or a benzyloxy group or halogenobenzyloxy group such as a chlorobenzyloxy group.

The C-C used in the process of the present invention. Alcoholate is an alkali metal alcoholate or an alkaline earth metal alcoholate such as potassium methylate, sodium methylate, sodium n-propylate, sodium iso-propylate, potassium ethylate, potassium n-propylate and potassium isopropylate.

When methylate is used, N-methylbenzanilide is formed as a by-product.

When methylate is used in conjunction with a compound of formula [I] wherein R is a methyl group, a large amount of N-methylbenzanilide is formed.

The solvent of the process of the present invention is important. The solvent is a compound of the general formula:

[IV] wherein R1 represents a lower alkyl group having 1-5 carbon atoms or a chlorine atom, R and R represents a hydrogen atom, a methyl group or a chlorine atom, or a compound of the general formula:

R - O - R

wherein R4 and R5 represent an n- or iso-butyl group or a C5-6 alkyl group.

Suitable solvents include the compounds of formula [IV] wherein: 1 2 3

1. R represents methyl, R represents Cl, and R

represents H or Cl, or 1 2 2. R represents Cl, R represents H or Cl, and 3 R represents H, or 1 2 3. R represents a C 1-6 alkyl group, and R and 3 R represent H.

Typical solvents are: o-, m- and p-xylene, o-, m- and p-ethyltoluene, o-, m- and p -propyltoluene, o-, m- and p-cymene, o-, m- and p-chloro-toluene, 2,4-, 2,5- and 2,6-dichlorotoluene, 3,4-dichlorotoluene, chlorobenzene, o-dichlorobenzene, m-dichlorobenzene, ethylbenzene, n-propylbenzene, cumene, n- butylbenzene, iso-butylbenzene, sec-butylbenzene, tert-butylbenzene, n-arayl-benzene, iso-amylbenzene, tert-amylbenzene, mesitylene, diethylbenzene, n- or iso-dibutyl ether.

When o-, m- or p-xylene or chlorobenzene is used as the solvent in the case where R in the compound [I] is an n-propyl group, or o-, m- or p-xylene, ethylbenzene or chlorobenzene in the case where R in the compound [I] is an n-butyl group or if solvent is used o-xylene, ethylbenzene or chlorobenzene in the case where R in the compound [I] is an isobutyl group degree of azeotropic distillation with the reaction produced as a by-product of alcohol.

Other solvents cause the following disadvantages:

Benzene or toluene produces an azeotropic distillation with the alcohol formed during the reaction as a by-product, making it difficult to obtain 2-substituted benzanilide in high yield.

When dimethylformamide is used, it reacts with the aniline to form formamidine as a by-product.

When alcohol and lower alkyl ethers are used, the reaction does not proceed smoothly or the product yield is not satisfactorily high.

When hydrocarbon chloride such as chloroform is used, it gives rise to side reaction.

The reaction of the present invention is usually carried out by reacting the 2-substituted alkyl benzoate [I] with the aniline [II] under atmospheric pressure and the presence of the particular alcoholate in the particular solvent under stirring and heating.

For example, the 2-substituted alkyl benzoate [I] is added to a mixture of the particular alcoholate and aniline [II] in the particular solvent with stirring and heating, or the particular alcoholate is added to a mixture of the 2-substituted alkyl benzoate [I] and the aniline [II] in the particular solvent.

The amount of the 2-substituted alkyl benzoate [I] is usually between 0.9 and 1.5 moles, preferably from 1 to 1.3 moles per mole. 1 mole of aniline [II].

The amount of the particular alcoholate is usually from 0.9 to 2.0 moles, preferably 1 to 1.5 moles per mol aniline [II] -

The reaction temperature is in a range of from 100 to 200 ° C, preferably from 120 to 150 ° C.

The reaction time is in a range of from 1 to 20 hours, preferably from 2 to 6 hours.

After the reaction, the 2-substituted benzanilide sought is usually in the form of alkali metal or alkaline earth metal salt. Generally, a mineral acid is added to hydrolyze the metal salt of the benzanilide.

However, by the process of the present invention, it is also possible to hydrolyze the metal salt of the 2-substituted benzanilide by adding water to the reaction mixture, thereby separating the 2-substituted benzanilide [III] in high yield.

The process of the present invention has the following characteristic features and advantages:

First, 2-substituted benzanilides which are useful as germicides and have not hitherto been able to be produced in high yield can now be produced in high yield.

Second, 2-substituted benzanilides can be prepared without the formation of N-alkylbenzanilides as a by-product.

Since N-alkylbenzanilide is not contained in the product, the 2-substituted benzanilides produced can be used as a germicide with stable and high germicidal action to control plant diseases.

The invention will now be described in more detail in the following examples.

Example 1

Preparation of 3t-iso-propoxy-2-methylbenzanilide In a 200 ml four-neck flask equipped with a stirrer, a thermometer, a condenser and a dropping funnel, 50 ml of p-xylene, 15.1 g ( 1 mole of m-iso-propoxyaniline and 37.4 g of 20% ethyl alcohol solution of sodium ethyl alcohol (0.11 mole as NaOC 3 H 2). The mixture was heated to 80 - 90 ° C to distill off the ethyl alcohol.

The mixture was heated to 130 ° C and 19.6 g (0.11 mol) of isopropyl-2-methylbenzoate was added dropwise to the mixture at 130 ° C over 30 minutes with stirring and the reaction continued for an additional 5 hours. The isopropyl alcohol product, which was formed by the addition of isopropyl-2-methylbenzoate, was distilled off during the reaction.

After the reaction, the reaction mixture was cooled and 50 ml of water was added to the reaction mixture, then 50 ml of n-hexane was added and the precipitated crystals were filtered off to give 25.6 g (yield 95.2%) of white crystals of 31-isopropoxy-2- methylbenzanilide (mp 91-92 ° C). Gas chromatography analysis confirmed that no by-products of N-alkyl-3-isopropoxy-2-methylbenzanilide had been formed. The purity of the product was 99.8%.

Example 2

According to the procedure of Example 1, reactions of various alkyl-2-methylbenzoates with m-isopropoxy-aniline were carried out in various solvents such as p-xylene, ethylbenzene and chlorobenzene.

When methyl 2-methylbenzoate was used, according to the results with all solvents, N-methyl-3, -isopropoxy-2-methylbenzanilide was prepared as a by-product. The yield of 3'-isopropoxy-2-methylbenzanilide in the reactions was as follows:

Table 1

x) Saitro equation nipples

As shown in Example 2, the yield was low when p-xylene was used as the solvent in the case where R is an n-propyl or n-butyl group. When ethylbenzene was used as the solvent in the case where R is an n-propyl or n-butyl group, the yield was low.

When chlorobenzene was used in the case where R is an n-propyl, n-butyl or iso-butyl group, the yield was also low.

Therefore, the reactions of the method of Example 2 were carried out using the β-cymene, cumene or mesitylene as solvent.

The results showed that the yield did not decrease and that 3'-isopropoxy-2-methylbenzanilide could be obtained in high yield of more than 90%.

Example 3

Preparation of 4 * -methoxy-2-methylbenzanilide In the flask of Example 1, 50 ml of cumene, 13.7 g (0.1 mole) of p-methoxyaniline and 37.4 g and 20% ethyl alcohol solution of sodium ethylate (0.11) were charged. mole as NaOC + H +). The mixture was heated to 80-90 ° C to distill off ethyl alcohol and 18.1 g (0.11 mol) of ethyl 2-methyl benzoate was added dropwise to the mixture at 130 ° C over 30 minutes with stirring and the reaction was continued for another 5 hours.

The ethyl alcohol by-product formed by the addition of ethyl 2-methylbenzoate was distilled off to alleviate the reaction.

After the reaction, react in the onion 1 was treated according to the procedure of Example 1 to give 25.0 g (yield 92.9%) of white needles of 41-methoxy-2-methyl-benzanilide (mp 149 to 149.5 ° C ).

Example 4

By the same procedure as that described in Example 3, various alkyl-2-methylbenzoates were reacted with m-iso-propylaniline in the presence of different alcoholates and different solvents to give 3'-iso-propyl-2-methylbenzanilide.

The results obtained are listed in Table 2.

Table 2

(x) Comparative equation examples

Notes: 1. In comparative experiments Nos. 4-101 and 102, the reaction was carried out by azeotropic distillation of the alcohol formed during the course of the reaction, together with the solvent benzene, under reflux conditions.

In Comparative Experiment Nos. 4-101, N-methyl-3'-iso-propyl-2-methylbenzanilide was formed in an amount of approx. 30% as a by-product, while no by-product was formed in Comparative Experiment No. 4-102.

2. In Comparative Experiments Nos. 4-103, the reaction was carried out by azeotropic distillation of the ethyl alcohol formed during the course of the reaction, together with the solvent toluene, under reflux conditions.

3. In comparative experiments Nos. 4-104 and 105, the reaction was carried out at 130 ° C and formamidine formed as a by-product.

4. In Comparative Experiments Nos. 4-106, the reaction was carried out at 170 ° C without using any solvent. A small amount of polymer formed as a by-product.

Example 5

Using the same procedure as that described in Example 1, the reactions were carried out using different alkyl-2-substituted benzoates and different anilines in the presence of different alcoholates and different solvents to prepare the corresponding 2-substituted benzanilides.

The results obtained are listed in Table 3.

Table 3

Table 3 (continued)

Table 3 (continued)

Table 3 (continued)

Claims (2)

A process for preparing a 2-substituted benzanilide of the general formula: [III] wherein X represents a halogen atom or a lower alkyl group, and Y represents a hydrogen atom, an alkyl, alkoxy, alkenyloxy, alkynyloxy, benzyloxy or halogenobenzyl oxy group, in which process an o-substituted alkyl benzoate with the general formula: [I] wherein X is as defined above and R represents an alkyl group is reacted with aniline of the general formula: [II] wherein Y has the meaning given above, in the presence of a C alcoholate of an alkali or alkaline earth metal as Z-4 catalyst and an organic solvent, characterized in that a mixture of the aniline compound, , and with the general formula: wherein R represents an alkyl group having 1-5 carbon atoms or 23 a chlorine atom and R and R represents a hydrogen atom, a chlorine atom or a methyl group, or a solvent of the general formula: * 4 - O - RS 4 wherein R and R represents an n- or iso-butyl or a C 1-6 alkyl group, with the exception of toluene, heated and thereby reacted with the o-substituted alkyl benzoate in which R represents a C 1-4 alkyl group. Process according to claim 1, characterized in that from a mixture of the solvent, aniline compound and a solution of the alcoholate in the corresponding alcohol, the alcohol is distilled off at a temperature of from 80 to 90 ° C and then the mixture is reacted with the o-substituted alkyl benzoate. at a temperature of from 125-150 ° C.