DE2221109C2 - Process for the preparation of α-anilincarboxylic acid nitriles - Google Patents

Description

NH,

(II)

with a cyano compound, characterized in that the aniline of the general formula (II), in which R ² and R ^{3 have} the meanings given, in a monohydric aliphatic alcohol having 1 to 6 carbon atoms, in 2-chloroethanol, in ethylene glycol or in a mixture of either of these alcohols

A) with hydrogen cyanide and an aldehyde of the general formula R ⁴ —CHO at a temperature between -20 and + 60 ° C or

B) with a cyanohydrin of the general formula R ^ CH (OH) -CN, where R ^{4 in} each case has the meanings given, in the presence of a strong base at a temperature of 50 to 100 ^° C.

2. The method according to claim 1, characterized in that the respective method in Ethanol carries out.

3. The method according to claim I or 2, characterized in that in process A) both Hydrogen cyanide and the aldehyde in an excess of 3 to 10 mol%, in particular 4 up to 7 mol%, calculated on the aniline, is used.

4. The method according to any one of claims 1 to 3, characterized in that in process A) adding the aldehyde to a mixture of hydrogen cyanide and the aniline in the respective alcohol.

5. The method according to claim 1 or 2, characterized in that in method B) the Cyanohydrin in an excess of 10 to 50 mol%, in particular from 20 to 40 mol%, calculated on the aniline.

6. The method according to any one of claims 1, 2 or 5, characterized in that method B) in Carries out the presence of a tertiary nitrogen base.

7. The method according to any one of claims 1, 2, 5 or 6, characterized in that one process

B) carried out in the presence of triethylamine.

8. The method according to any one of claims 1, 2 or 5 to 7, characterized in that in process B) the tertiary nitrogen base in an amount of 0.3 up to 10 mol%, calculated on the cyanohydrin, is used

^{9. The method according to any one of claims 1,} 2 or 5 to 8, characterized in that method B) is carried out at a temperature of 60 to 80.degree.

10. The method according to any one of claims 1, 2 or 5 to 9, characterized in that one process B) in ethanol at the boiling point of the Carries out reaction mixture.

The invention relates to a process for the preparation of α-anilinocarboxylic acid nitriles, some of which

represent new compounds and which serve as starting compounds for the production of herbicides can.

It is known that anilines substituted in the benzene nucleus with aldehydes and alkali metal cyanides - z. B. with Formaldehyde or acetaldehyde and KCN - in an aqueous acidic medium to a-anilinocarboxylic acid nitriles can implement (DE-OS 20 09 387; J. Med. Chem. 8, page 332/3, 1965). The yields are at these Procedure at about 62 to 68%.

It has now been found that anilines substituted in the benzene nucleus also contain hydrogen cyanide and an aldehyde or a cyanohydrin can be reacted and that these reactions to Much improved yields of over 90% result when in a given alcoholic Medium.

The invention relates to the method for the production of nc-aminocarboxylic acids! trile.

The nitriles which can be prepared according to the invention correspond to the general formula

VNH-CH-CN

R ⁴

so in which the substituents R ² , R ³ , R ^{4 have the} following meanings:

R ² is hydrogen, chlorine, fluorine, alkyl, haloalkyl, or alkoxy; R ³ is chlorine or fluorine and R ⁴ is hydrogen or alkyl. If R ^{2 is} an alkyl, a haloalkyl or an alkoxy group and / or R ^{4 is} an alkyl group, these groups contain no more than 6 carbon atoms, while the halogen atom (s) of the haloalkyl group is, in particular, chlorine and / or fluorine. are. The groups mentioned can be either branched or unbranched. Examples of such groups are: methyl, ethyl, propyl, η-butyl, trifluoromethyl and methoxy, of which the methyl group is the most preferred alkyl group. Preferably R ^{2 is} hydrogen or Cl; and R ^{4 is} CH ₃ .

The substituents R ² and R ³ can occupy any free position in the benzene nucleus. Examples of nitriles of the formula I which can be prepared according to the invention are

the various isomeric mono- and dichloro compounds, such as the 2-, 3- and 4-chloro and the 3,4- and 2,5-dichloro compounds; the fluorine and fluorine chlorine compounds, especially the 4-fluorine, 4-chlorine, 4-chloro-3-fluorine and 3-chloro-4-fluorine compounds and the methyl-chlorine, (trifluoromethyl) -chlorine and Methoxy-chlorine compounds, such as the 2-methyl-4-chlorine, the 4-methyl-3-chlorine, the S-trifluoromethyl ^ -chlorine and the 2-methoxy-4-chlorine compounds. Particularly preferred compounds are the 4-chloro, 4-fluoro, 4-chloro-3-fluoro and 3-chloro-4-fluoro compounds and in particular the 3,4-dichloro compound, as well as the anilinoacetonitriles in question (R ⁴ = H) and in particular the propionitriles (R ⁴ = CH3).

For the preparation of the a-anilinocarboxylic acid nitrile leaves a correspondingly substituted aniline of the general formula

in which R ² , R ³ and R ^{4 have} the same meaning as in formula I, in a monohydric aliphatic alcohol with 1 to 6 carbon atoms, in 2-chloroethanol, in ethylene glycol or in a mixture of these alcohols with either (A) Hydrogen cyanide and an aldehyde, R ⁴ -CHO, or with (B) a cyanohydrin. R ⁴ -CH (OH) -CN, react; in case (B) the reaction takes place in the presence of a strong base.

Particularly preferred anilines (II) are those in which R ^{2 represents} H or Cl. Examples of usable anilines are the various isomeric mono- and dichloroanilines, the fluoro- and fluoro-chloroanilines, the methyl-chloro-, (trifluoromethyl) -chloro and methoxychloroanilines. Preference is given to using 4-chloroaniline, 4-fluoroaniline, 4-chloro-3-fluoroaniline, 3-chloro-4-fluoroaniline and, in particular, 3,4-dichloroaniline.

The aniline (II) is preferably reacted with HCN and an aldehyde of the general formula R ⁴ -CHO, in which R ^{4 has} the above meanings. Particularly suitable aldehydes are formaldehyde (R ⁴ = H) and in particular acetaldehyde (R ⁴ = CH ₃ ). Favorable results are generally obtained when both HCN and the aldehyde are present in a molar excess, preferably from 3 to 10 mol%, in particular from 4 to 7 mol%, calculated on the aniline.

According to a preferred embodiment, one works so that the aldehyde to one Mixture of HCN and the aniline in the alcoholic medium described above, although also other methods can be used such as the simultaneous addition of aldehyde and HCN to the Aniline.

The reaction is conducted at a temperature between - 20 and preferably carried out + 6O ⁰ C is between 10 and 25 and especially between 15 and 20 ⁰ C under atmospheric pressure, but also pressure may be applied.

According to the second embodiment of the process, the aniline (II) is reacted with a cyanohydrin of the general formula R ⁴ —CH (OH) —CN. In practice, the cyanohydrin is used in an excess of preferably 10 to 50 mol%, in particular 20 to 40 mol%, calculated on the aniline compound.

In this case, too, the reaction must be carried out in the alcoholic medium mentioned above, ethanol preferably being used. In this case, however, a strong base must also be present in the reaction medium, e.g. B. a base with a pK _a value of at least 9. Examples are alcoholates such as sodium ethylate, alkali hydroxides such as NaOH and KOH, preferably used in a solid carrier such as silica or alumina, in particular γ-alumina; a basic anion exchanger, e.g. B. of the tertiary amino or quaternary ammonium type, in particular a commercially available anion exchanger with trialkylammonium or dialkylhydroxyalkylammonium groups. Organic bases, especially tertiary nitrogen bases, are preferred and particularly favorable results are obtained in an aliphatic tertiary amine in which two or more alkyl groups can be the same or different, but each alkyl group preferably contains no more than 6 carbon atoms. Examples are: triethylamine, triisopropylamine, tri-n-butylamine and triethanolamine.

Particularly good results have been obtained with triethylamine. The amount of tertiary nitrogen base is generally from 0.3 to 10, preferably from 2 to 6, mol%, calculated on the cyanohydrin used.

The appropriate for implementing a cyanohydrin with the aniline temperatures are between 50 and 100 and preferably between 60 and 8O ⁰ C. When a

If a low-boiling alcohol such as ethanol is used as the reaction medium, the boiling point is the Reaction mixture is the particularly preferred reaction temperature.

According to the invention, it is essential that both embodiments (A) and (B) in the alcoholic Reaction medium are carried out so that excellent yields of nitrile are obtained. With On the other hand, other types of solvents, such as diethyl ether, dimethylformamide, toluene or xylene, are formed undesirable by-products in significant amounts and the yield of the desired nitrile remains in the Usually unsatisfactory. The same applies to the presence of the base in embodiment (B). Became no strong base was used here, the nitrile was only in extremely small amounts, if at all educated.

The nitriles (I) produced according to the invention are inter alia. particularly suitable starting materials for production of herbicidally active α-anilinocarboxylic acid esters.

Some of the nitriles which can be produced according to the invention have not yet been produced. New connections are e.g. B. <% - (4-fluoroanilino) -propionitrile and a - (\ - chloro-3-fluoroanilino) -propionitrile. Some nitriles (1) have herbicidal properties themselves.

The examples serve to explain the invention in more detail.

example 1

Production of

λ- (3,4-dichloroanilino) propionitrile from
3,4-dichloroaniline, acetaldehyde and HCN

In one with stirrer, inlet, reflux condenser and thermometer equipped 5-liter four-necked round bottom flask, 91.5 g (3.389 mol) of HCN at 0 introduced to 10 ⁰ C, after which 521.5 g (3.22 mol) of 3,4-dichloroaniline and 2.3 liters of ethanol (96%) were added. The temperature was then allowed to rise to 15 ° C. and gave

gradually 149.1 g (3389 mol) of acetaldehyde with stirring over the course of one hour. After stirring for a further half hour at room temperature, the mixture was ^{heated to 60 °} C. for half an hour in order to dissolve the crystalline precipitate formed, and then allowed to cool again to room temperature. The deposited as a crystalline mass reaction product was abfihriert in vacuo at about 70 ⁰ C and 12 to 20 mm of Hg were 542 g (2.52 mole) of a- (3,4-dichloroanilino) -propionitrile, mp. 118 to 119 to ° C, degree of purity 99%. The yield was 78.3%, calculated on the 3,4-dichloroaniline added.

A further portion was obtained from the filtrate by stripping off the volatile constituents in a thin-film evaporator at 40 to 50 ^° C. (bath temperature) and 12 to 15 mm Hg and subsequent crystallization from ethanol; this increased the yield to 98%.

Was the procedure for comparison under otherwise identical conditions in non-alcoholic media carried out, so much poorer yields were obtained, namely 75 to 80% in diethyl ether, 50 up to 60% in dimethylformamide and 40 to 50% in toluene.

It has proven to be advantageous not to isolate the dissolved product from the filtrate, but rather that Filtrate for further reaction with fresh starting material under the same conditions as above in the Return reaction vessel. In this way you get an almost quantitative yield and also the new one The filtrate can be fed back into the circuit.

Example 2
Production of «- (4-ChloraniIino) -propionitrile

35

4-chloroaniline (25.5 g, 0.2 mol) and hydrogen cyanide (39 ml) in 96% ethanol (300 ml) were ^{stirred together at 15 °} C. and acetaldehyde (56 ml) was added to the mixture over the course of one hour. The mixture was then stirred for a further hour at 15 ° and then at 60 ° for two hours, the mixture was left to stand at room temperature for 16 hours and then poured into water (500 ml). The product which crystallized out of the solution and was filtered off melted at 113 to 116 ° C; Yield 33 g, 91% based on 4-chloroaniline.

Example 3

In the same manner as in Example 2, the following were not previously described in the literature Connections made:

(a) α- (4-FluoroaniIino) -propionitrile

This compound with a melting point of 71 ° to 73 ° C. was obtained in 91% yield, calculated on that used 4-fluoroaniline.

Analysis for C ₉ H ₉ FN ₂ :

Ber. C 65.9, H 5.5, N 17.1%,
Found C 66.3, H 5.6, N 17.0%.

(b) «- (4-Chloro-4-fluoroanilino) propionitrile

This compound of m.p. 130-132 ° C was also obtained in 91% yield, calculated on the 4-chloro-3-fluoraniline used.

Analysis for C ₉ H ₈ ClFN ₂ :

Ber. C 54.4, H 4.0, N) 4.1%,

Found C 54.7, H 4.1, N 14.2%.

Example 4

Production of

«- (3,4-Dichloroanilino) -propionitrile from
3,4-dichloroaniline and α-hydroxypropionitrile

In a 500 ml flask equipped with a stirrer and reflux condenser, 81 g (0.5 mol) of 3,4-Dichlorani-Hn, 46.1 g (0.65 mole) oc-hydroxypropionitrile, 100 ml Ethanol (96%) and 2.6 g (0.025 mol) of triethylamine introduced and with stirring to reflux temperature brought and held there for 3 hours, whereupon all 3,4-dichloroaniline had reacted. After adding 150 ml of ethanol was allowed to cool the mixture to room temperature. The resulting crystalline Precipitate was filtered off, washed with 25 ml of ethanol and yielded after the ethanol had been stripped off 50 ° C / 20 mm Hg <x- (3,4-dichloroanilino) propionitrile with a melting point of 118 to 119 ° C.

After concentrating the mother liquor to about 25 ml and cooling it to 10 ° C., another one was obtained therefrom crystalline precipitate which was washed and dried as above. The overall yield increased thereby to 86 g, which corresponds to a yield of 80%, calculated on 3,4-dichloroaniline.

Claims (1)

Patent claims: 1. Process for the preparation of -anilinocarboxylic acid nitriles the general formula (D in which R ^{2 is} hydrogen, chlorine, fluorine, alkyl, haloalkyl or alkoxy, R ^{3 is} chlorine or fluorine and R ^{4 is} hydrogen or alkyl, the alkyl, haloalkyl and alkoxy groups having no more than 6 carbon atoms, by reacting an appropriately substituted one Aniline of the general formula