DE2221109A1 - Process for the preparation of alpha-aniline carboxylic acid esters and nitriles - Google Patents

Description

"Process for the preparation of alpha anilinocarboxylic acid esters and nitriles "

The invention relates to a method of manufacture of ot-anilinocarboxylic acid esters from the corresponding Nitriles. It also relates to the production of these nitriles themselves, some of which are novel compounds represent. The products made according to the invention. are useful as effective herbicides.

Process for the direct conversion of nitriles, such as a- (N-alkylamino) -carbonitriles, into the corresponding Carboxylic acid esters by alcoholysis are well known. However, difficulties arise when the exit

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ORIGINAL INSPECTED

The starting material is an α-anilinocarbonitrile. So you get usually in this case unsatisfactory yields due side reactions occurring, such as the splitting off of the aniline group, while in other cases the desired one Implementation requires very long response times. In addition, the isolation of the compounds obtained is often expensive Procedures connected.

According to BPS 1 112 069 it is not possible to produce an α-anilinocarboxylic acid ester from the corresponding nitrile by the direct action of an absolute alcohol in the presence of either hydrochloric acid or concentrated sulfuric acid. This has been demonstrated by various unsuccessful attempts in this direction, which are described in Example 1 of the patent mentioned. The negative results of these experiments actually show that the desired carboxylic acid ester, for example from α-anilinoisobutyronitrile, could not be obtained when the reaction with, for example, methanol was carried out either at room temperature or at the boiling point of the mixture. According to the teaching of this patent, the conversion of ot-anilinocarbonitriles into the corresponding esters could only be achieved by first reacting the nitrile with concentrated or fuming H ₂ SO ^ - so that salt formation, accompanied by the addition of sulfuric acid to the nitrile group , took place - and then heated the reaction mixture with the alcohol; the successive addition of H ₂ SO ^ and the alcohol is essential in this process.

It has now been found that the above-mentioned disadvantages

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avoided and high yields can be achieved if the ITitrile in question in the presence of chlorine or Can hydrogen bromide react with an alcohol, provided that the temperature and reaction time as well as the The amount and concentration of hydrogen halide is suitable Way of how to proceed, to be chosen. These responses are preferably in simultaneous attendance of the alcohol and the hydrogen halide.

The process according to the invention for the preparation of cx-anilinocarboxylic acid esters of the general formula: .- '-... ■ ";". -,

CH - X

Ί? 'S ■■
where E, E and TSr each represent a halogen atom or an alkyl,

1 haloalkyl or alkoxy group represented, but where E

and / or E also hydrogen atoms and E also one

-NH-CH (E ⁴ ) -X- group or a - (A) _n -C ₆ H ₂ (E ¹ B ⁵ ) -NH-CH (E ⁴ ) -X- group, in which A = CHq, 0 , S or NH and η = zero or 1

4th
may be during E group represents a hydrogen atom or an alky], and X represent a Carbonsäureestergruppe ,, characterized in that _f 'is a nitrile of general formula:

2 0 9 8 A 7/1 1 9 1

NH-CH- CN (II)

wherein R, R, R, R have the above meaning, in the presence of hydrogen chloride or hydrogen bromide reacts with a primary or secondary alcohol}, initially

(a) at a temperature of -20 to + 7O ⁰ C and as long as that required for the reaction of at least 70% of the nitriles time is not exceeded, and then

(b) at a temperature of 55 to 15O ⁰ C, with the proviso that at least during the time interval

(a) the amount of HCl or HBr is greater than 3 »5 equivalents, based on the nitrile, while the concentration of the hydrogen halide in question in the reaction medium is at least 4 mol per liter.

The symbols r ' ¹ , R ² ,' R ^ and R ^ in formulas I and II preferably have the following meanings:

R ¹ = H {R ² = H, halogen, alkyl, haloalkyl or alkoxy;

■ ζ η

Ή. = Halogen and R = H or alkyl. The halogen atom or atoms can be, for example, chlorine, fluorine and / or bromine

be, among which chlorine and fluorine are preferred. If R is for an alkyl, a haloalkyl or an alkoxy group and / or R represents an alkyl group, contain these groups preferably no more than 6 carbon atoms, while that or the halogen atoms of the haloalkyl group, in particular chlorine

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and / or fluorine is or are. The groups mentioned can be both acyclic (branched or unbranched) as well as cyclic, examples of such groups are: methyl, ethyl, propyl, η-butyl, trifluoromethyl and methoxy, of which the methyl group is the "most preferred alkyl group. Particularly preferred nitriles Formula II, which can serve as starting materials, are those in which E ¹ ^ H; E ² = H or Gl; E ³ = Cl or F and R ⁴ = CH ₃ .

The substituents E and E ^ can, generally speaking, occupy any free position in the benzene nucleus. Examples of useful nitriles of the formula II are various isomeric mono- and dichio derivatives, such as the 2-, 3- and 4-chloro and the 3,4- and 2,5-dichloro derivatives; the fluorine and fluorine chlorine derivatives, especially the 4-fluorine, 4-chlorine, 4-chloro-3-fluorine and 3-chloro-4-fluorine derivatives and the methyl chlorine, (trifluoromethyl) chlorine and methoxychlorine derivatives, such as the 2-methyl-4-chloro, the 4-methyl-3-chloro, the 3-trifluoromethyl-4-chloro and the 2-methoxy-4-chloro derivatives, where the number 1 is the carbon atom ^ denotes the phenyl group on which the N atom is located. Particularly preferred compounds are the 4-chloro, 4-fluoro, 4-chloro-3-fluoro and 3-chloro-4-fluoro derivatives and especially the 3i4 dichloro derivative. It has also proven advantageous of the anilinoacetonitriles (E = H) or -propiononitriles in question (E = CH,), of which the latter especially are recommended. Excellent results, for example obtained with ct- (3,4-dichloroanilino) propiononitrile.

In the process according to the invention, the nitrile (II) is left

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react with a primary or secondary alcohol in the presence of hydrogen chloride or hydrogen bromide, hydrogen chloride being preferred. The hydrogen halide is expediently used in the form of a solution in the alcohol used; for example, a solution which contains the necessary amount of HCl or HBr in the alcohol can be added to a solution of the nitrile in the same alcohol. Often it is also possible to introduce the gaseous hydrogen halide in the reaction mixture, especially when at relatively low temperature, for example at O to 2O ⁰ C, operates. In general, it is advisable to work in the absence of water, although a small amount of water, ie about 1 to 5 % of the weight of the reaction mixture, is often not harmful. However, if higher amounts of water are present, the simultaneous hydrolysis of the nitrile will impair the formation of the desired ester. Examples of particularly useful alcohols are: methanol, ethanol, isopropyl alcohol, 2-chloroethanol and ethylene glycol. Primary alcohols, in particular ethanol, are preferred.

As a rule, at least the required stoichiometric amount of alcohol should be used in the reaction with the nitrile. Very favorable results are obtained when the alcohol is used in excess, the excess serving as a solvent and / or diluent for the reaction mixture. It has thus proven advantageous to use the alcohol in an amount which is sufficient to keep the reaction components in solution. Smaller amounts can of course also be used, especially if the excess is wholly or partially replaced by one or more other solvents or diluents, for example by an ether such as 1,2-dimethoxy- ^s "

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ethane, dioxane or tetrahydrofuran.

According to the invention allows the reaction first at a! Temperature between -20 and +70 ⁰ C in the presence of HBr HOl or run in the appropriate amount, it being understood that the Heaktionsgemisch not long under these conditions is left than is necessary, in order to implement a conversion of at least 70 % - preferably at least 90 and in particular 95 to 99 % - of the nitrile. The progress of the reaction can easily be followed by analyzing samples taken from the reaction mixture at regular intervals, for example with the aid of a GLC analysis. Recommended temperatures are, generally speaking, between 30 and 65 ⁰ C, with a temperature of 40 to 60 and especially from 45 is preferably up to 55 ° C. _; ·

The amount of HCl or HBr that is present at least during the first period mentioned above must, should be more than 3j5 equivalents, calculated on the Nitrile, and is generally between 4.5 and 30, preferably between 5 and 15 equivalents in particular 8 to 10 equivalents, each calculated on the nitrile, although larger amounts are also possible. Another essential condition for the success of the procedure is that the concentration of the relevant Hydrogen halide is at least 4 moles per liter of reaction medium. Suitable concentrations for Generally speaking, HCl and HBr are within a range of 5 to 20 mol / liter, with concentrations of 6 to 10 and especially from 7 to 9 mol / liter are preferred. In certain cases, however, are even higher Concentrations possible.

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At relatively low temperatures, for example from 0 to 20 ^° C., as a rule only a relatively small amount of hydrogen halide has to be present. However, the reaction is usually relatively slow under these conditions. Although this can be improved by increasing the amount of hydrogen halide, the large amounts which must be used in order to achieve a satisfactory reaction rate under these conditions are often unsuitable for practical purposes. In addition, it has been found that an increase in the concentration of HCl or HBr leads to an increase in the reaction rate under otherwise identical conditions. If, on the other hand, one works at higher temperatures and relatively low concentrations of HCl or HBr, then, owing to the predominance of side reactions, such as the splitting off of the aniline half, only little or no yields are obtained. Surprisingly, it has now been found that the side reactions can be suppressed simply by using the hydrogen halide in higher concentrations when working at higher temperatures. Thus, for any temperature within the above-mentioned range, an optimal range for both the amount and the concentration of HCl or HBr can be selected in such a way that the reaction proceeds at a satisfactory rate. Although the amount of hydrogen halide can exceed the above-mentioned ranges, it is usually advisable, for economic and practical reasons, not to use more hydrogen halide than is necessary.

If the desired reaction of the nitrile in the first temperature range, ie at -20 till. + 7O ⁰ C is reached, the reaction mixture is according to the invention further reacted at a

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Temperature from 55 to 150, preferably between 70 and 10O ⁰ C. It is generally advisable to work at a higher temperature than in the first stage, ie the reaction mixture is heated to a higher temperature, preferably to boiling. The heating time in the second temperature range is generally not critical However, the heating should not be continued for longer than is necessary to form the desired product. If necessary, the process can also be carried out in such a way that the reaction mixture is gradually heated, for example from room temperature to the boiling point. In certain cases the first and the second temperature range overlap. It is also possible, for example, to work only at one temperature which is in the overlap range. However, it is preferred to heat the action mixture successively within two relatively narrow temperature ranges. For example, excellent results were obtained when the reaction of α- (3,4-dichlaranilino) propiononitrile mi t ethanol was carried out initially at 40 to 55 ⁰ O and then at the boiling point.

The isolation of the α-anilinocarboxylic acid ester can e.g. be carried out by evaporating the alcohol, subsequent. Addition of water and extraction with an organic solvent such as toluene.

By acylation of the α-anilinocarboxylic acid esters prepared according to the invention the corresponding N-acyl derivatives are obtained, which are valuable compounds with herbicidal action (see BPS 1 164 160). They are particularly applicable to selective control of wild wheat in cereal plantations.

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Excellent results are obtained when the active compound, for example, the ethyl ester of α- (ΙΓ-Beriz oyl 3 »is 4-dichloroanilinopropionic acid.

The invention also relates to a method for Preparation of oc-anilinocarbonitriles of the above general Formula II, which is characterized in that an aniline compound of the general formula:

(III)

in an alcoholic medium can react with either. (aj hydrogen cyanide and an aldehyde, R -CHO, or

(b) a cyanohydrin, R ^ -CH (OH) -CN, where in case (b)

1 2 ⁵ S a strong base is also present; R ₁ R, ~ Br and

R in formula III have the same meaning as in formula I and II.

Particularly preferred aniline compounds (III) are those in which R ^ is H, R is H or Cl and Br is Cl or F. Examples of usable anilines are the various isomeric mono- and dichloro derivatives, the fluorine and fluorochlorine derivatives, the methylchlorine, (trifluoromethyl) chlorine and methoxychlorine derivatives. Deserve the preference: 4-chloroaniline, 4-fluoroaniline, 4-chloro-3-fluoro-

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aniline, 3-chloro-4-fluoroaniline and especially 3 »4-dichloroaniline. .

The aniline compound (III) is preferably reacted with HGN and an aldehyde of the general formula E -CHO ₁ in which E is preferably a hydrogen atom or an alkyl group having not more than six carbon atoms, such as methyl, ethyl, propyl or η-butyl. Particularly suitable aldehydes are formaldehyde (E = H) and in particular acetaldehyde (E = CH,). Favorable results are obtained. generally when both HCN and the aldehyde are present in a molar excess, preferably from 3 to 10, in particular from 4 to mol%, calculated on the aniline compound. · ·

According to a "preferred embodiment, one works so that the aldehyde is added to a mixture of HCN and the aniline compound in the alcoholic medium, although other methods can be used, such as the simultaneous addition of aldehyde and HCN to the Aniline compound.

The alcohol used as the reaction medium is preferably an aliphatic, mono- or polyhydric alcohol (branched or unbranched), the optional substituents may contain. Alcohols with no more than six carbon atoms are generally preferred, e.g. methanol, Ethanol, isopropyl alcohol, 2-chloroethanol and ethylene glycol. Excellent results were achieved in particular with ethanol. Mixtures of several alcohols and / or others Solvents or diluents can of course also be used.

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The reaction is usually carried out at a temperature between -20 and +60 ⁰ G, preferably between 10 and 25 and in particular between 15 and 20 ° 0 and under atmospheric pressure, but also pressure may be applied.

According to another embodiment, the aniline compound (III) is reacted with an oyanhydrin of the general type IOrmel R-CH (OH) -CN, a derivative of the above mentioned aldehyde R-CHO. In practice, the cyanohydrin is preferably used in an excess of 10 to 50, in particular 20 to 40 mol%, calculated on the aniline compound.

In this case too, the reaction must be carried out in an alcoholic medium, alcohols of the above type, among which ethanol is preferred, being suitable. In addition, in this case, however, a strong base must still be present in the reaction _{medium, for example a base with a pK &} value of at least 9. Examples are alcoholates such as sodium ethoxide, alkali hydroxides such as NaOH and KOH, preferably used in a solid carrier such as Silica or alumina, especially γ-alumina; a basic anion exchanger, for example of the tertiary amino or quaternary ammonium type, in particular an anion exchanger with trialkylammonium or dialkylhydroxyalkylammonium groups, for example an "Amberlite" resin, such as IRA-400 and IRA-904- or an "Amberlyst" resin, such as A- 26 and A-29, "Deacidite" FF, "Dowex" 1, "Duolite" A-42, "Nalcite" SBR, "Permutit" ESB, "Wofatit" L-165 and "Levatit" MN. Organic bases, especially tertiary nitrogen bases, are preferred and particularly favorable results are obtained with

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an aliphatic tertiary amine in which two or more alkyl groups can be the same or different, but each alkyl group preferably no more than 6 carbon contains 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 in generally at 0.3 to 10, preferably 2 to 6 mol%, calculated on the cyanohydrin used.

Usually to implement a cyanohydrins with the aniline compound suitable temperatures are between 50 and 100 and preferably between 60 and 8O ⁰ C. When a low-boiling alcohol, such as ethanol, is used as the reaction medium, so the boiling temperature of the reaction mixture is the most preferred reaction temperature.

According to the invention it is essential "in both reaction stages (a) and (b) to use an alcoholic reaction medium and excellent yields were obtained in this way obtained on nitrile. However, other types of solvents such as diethyl ether, dimethylformamide, toluene or When xylene is used, significant amounts of undesired by-products are formed and the yield of Nitrll (II) was generally not at all satisfactory. If no strong base was used in the second reaction step (b), so the citrile was formed in extremely small quantities, if at all.

The nitriles (II) according to the invention include _{o o} a particularly suitable starting materials for the manufacture of d ^ r a-Anilinocarbonsäureester the above formula I ₀ in many cases

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the nitrile in alcoholic solution can be used directly in the synthesis of these carboxylic acid esters. A number of the nitriles in question have not yet been produced. Novel compounds are, for example, a- (4-i ^1- luoroanilino) -propiononitrile and a- (4-chloro-3-fluoroanilino) -propiononitrile. -

Some of the nitriles of the general formula II have herbicidal properties.

A particularly attractive embodiment of the invention is that one can use the two manufacturing methods mentioned above contracts into a single one, which can then be used to produce valuable herbicides. For this purpose, an aniline compound (III) is used with HCN and an aldehyde, R -CHO, or a cyanohydrin, E-CH (OH) -CN and subjects the resulting nitrile (II) then alcoholysis, so that a carboxylic acid ester is obtained, which is finally acylated. This method can be carried out either entirely or partially in batches, continuously or semi-continuously. So you can e.g. ethyl-a- (N-benzoyl-3> 4-dichloroanilino) propionate in produce good yield from 3j4-dichloroaniline, HCN and Acetaldehyde via the resulting, α- (3 »4-dichloroan ^ lino) -propiononitrile and the ethyl ester of the corresponding carboxylic acid.

The examples serve to explain the invention in more detail.

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example 1

Production of oc- (3,4-dichloroanilino) propiononitrile from 3,4-dichloroanil: m, acetaldehyde and HON

In one with a stirrer, a supply port, and thermometer equipped Bückflußkühler 5- * i "iter four-necked round bottom flask 91.5 g (5.389 mol) of HCN were introduced at O to 1O ⁰ C, whereupon 521.5 g (3.22 mol) of 3» 4-dichloroaniline and 2.3 l of ethanol (96% ) were added. Then the temperature was allowed to rise to 15 ⁰ O-and gave gradually 149.1 g (3.389 mol) of acetaldehyde under stirring within one hour. After half an hour further stirring at room temperature, the mixture was half an hour at 60 ⁰ G heated to the formed crystalline precipitate to dissolve, then allowed to cool back to room temperature. The reaction product deposited as a crystalline mass was filtered off and ^{dried in vacuo at about 70 °} C. and 12 to 20 mm Hg. 542 g (2.52 mol) of a- (3,4-dichloroanilino) propiononitrile, Ip. 118 to 119 ⁰ C, degree of purity 99% obtained. The yield was 78.3%, calculated on the 3,4-dichloroaniline added.

A further portion was obtained from the piltrate by stripping off the volatile constituents in a 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 %. The product thus obtained was combined and used for the reactions described in Examples 5 and 6.

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If, for comparison, the process was carried out under otherwise identical conditions in non-alcoholic media, the yields obtained were significantly poorer, namely 75 to 80 % in diethyl ether, 50 to 60% in dimethylformamide and 40 to 50 % in toluene.

Instead of isolating the dissolved product from the filtrate, it has proven advantageous to return the latter to the reaction vessel for further reaction with fresh starting material under the same conditions as above. In this way, an almost quantitative yield is obtained and the new filtrate can also be fed back into the cycle.

Example 2

Production of α- (4-chloroanilino) propiononitrile

4-chloroaniline (25.5 g _t 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. Stirring was then continued at 15 ° for an additional hour and then at 60 ° for two hours, after which it was allowed to stand for 16 hours at room temperature and then poured into water (500 ml). The crystallized from solution and filtered off product melted at 113 to 116 ⁰ Oj yield 33 g of "91%" based on 4-chloroaniline.

Example 3

In the same way as in Example 2, the following compounds not previously described in the literature were tasx> -

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posed:. ·.

(a) α- (4-ff luoraTn.linfl-prop! ononitrile

This compound, mp. 71 to 73 ⁰ C, was obtained in 9i% yield, calculated on the used 4-fluoroaniline. · .- ■: -. ^^ ^. Analysis: Ber. for OqHqM ₂ : 65.9 5.5 17.1% Found: 66.3 5.6 17.0%

(b) α- (4-Chloro-4-fluoroanilino) propiononitrile

This compound of melting point 130 to 132 ⁰ O was also calculated in 91% yield. the 4-chloro-3-fluoroaniline used. CHN analysis; Ber. for CqH ₈ CLI ¹ N ₂ : 54.4 4.0 14.1 %

Found: ν 54.7 4.1 14.2 %

B e i s ρ i e 1 .4

Preparation of a- (3,4-dichloroanilino) propiononitrile from 3,4-dichloroaniline and α-hydroxypropiononitrile

81 g (0.5 Hol) of 3,4-dichloroaniline, 46 »16 (0.65 mol) of α-hydroxypropiononitrile, 100 ml of ethanol (96 %) and 2 6 g (0.025 Hol) of triethylamine were introduced and brought to reflux temperature with stirring and held there for 3 hours, after which all the Si ^ dichloroaniline had reacted. After the addition of 150 ml of ethanol, the mixture was allowed to cool to room temperature. A crystalline precipitate was then filtered off with 25 ml

20 9 8 47/1191

Ethanol washed and gave after stripping of the ethanol at 50 ° C / 20 mm Hg a- (3,4-dichloroanilino) -propiononitril of mp. 118-119 ⁰ C.

After concentrating the mother liquor to about 25 ml and cooling it to 10 ⁰ O, another crystalline precipitate was obtained therefrom, which was washed and dried as above. The total yield increased to 86 g, which corresponds to a yield of 80%, calculated on 3 _i 4-dichloroaniline. '· -. .

Eg .pie 1 5.

Production of ethyl α- (3,4-dichloroanilino) propionate

(a) 21.5 g (0.1 mol) of oc- (3,4-dichloroanilino) propiononitrile (prepared according to Example 1) and 50 ml of absolute alcohol were introduced into a 250 ml three-necked flask equipped with a stirrer and reflux condenser, whereupon a solution of 29 g (0.8 mol) of HCl in 50 ml of absolute ethanol was added to the mixture in one portion at 20 ^{° C. with stirring.} The solution was then heated to 50 ⁰ C (oil bath temperature) and held h 3, wherein the reaction of the starting material increased to 98%. The suspension was then kept at reflux temperature for a further 3 1/2 hours, the excess ethanol was evaporated off in vacuo and 100 ml of water and 100 ml of toluene were added to the residue. After the bubbles had separated, the upper organic layer was washed twice with 100 ml of saturated aqueous soda solution _{, dried over anhydrous Na ^ SO 2} , and the solvent was driven off in vacuo.

In this way, 22.5 g of ethyl-a-

2 0 9 8 4 7/1 1 S 1

(3,4-dichloroanilino) propionate. Recrystallization from η-hexane gave 19.1 g of ale white crystals which ^{melted at 38 to 39 °} C. (degree of purity 96 %) ; Yield 73 % of theory ,. '-

(b) If the same conditions as under (a) were used, but at lower temperatures in the first heating period, it was found that longer reaction times were required at these temperatures in order to obtain analogous results. Table I shows the degree of conversion of α- (3 »^ - dichloroanilino) propiononitrile, which was obtained at 30, 40 and 50 ^° C. after various periods of time.

TABEL

Tempera conversion in% after

door in ⁰ C

1h. 2 h 3 h 4 h 5 h 6 h

- - 60 65 87 96 95 98 _

30 - - - 60 75 40 - 65 87 96 98 50 79

(c) The effect of increasing hydrogen halide concentrations was shown in tests in which 0.1 mol of α- (3 »4-dichloroanilino) propiononitrile and 100 ml of absolute

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Alcohol was used; the reaction mixture was heated over a half hour at 55 ⁰ C, held for one hour at this temperature and then heated within a further hour at reflux, at which it was held finally two hours. If the amounts of HCl used were 0.8 mol, 1.0 mol or 1.2 mol, yields of 87 »5, 79» 6 and 69.1 % ethyl-a- (3j4-dichloroanilino) were obtained. -propionate. The decrease in the yield is mainly due to a subsequent hydrolysis of the ester formed. If, on the other hand, the amount of HCl used was less than 0.8 mol, all other things being equal, a tendency towards elimination of 3-4-dichloroaniline was found.

Example 6 (comparative tests)

The following tests, which are only used for comparison purposes, show that the results are unsatisfactory Results obtained when one or more reaction conditions, such as the concentration or the amount of HOl and / or the temperature is not in accordance with the requirements.

(a) 0.01 mole of oc- (3,4-dichloroanilino) propiononitrile was with 0.04 mol HCl and 30 ml absolute ethanol heated to 50 to 55 ° C. Even after one had Heating for 20 1/2 hours almost no reaction of the starting material took place, since both the amount as the concentration of the HCl present were too low.

Experiment (a) was carried out with 0.08 mol of HCl and 40 ml

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absolute ethanol, also at 50 to 55 ⁰ O, so after 20 1/2 hours a part of the starting material had reacted. However, even if the reaction mixture was boiled for a long time, the ester yield could not be increased by more than 40% . Although the amount of HCl was sufficient in this case, the HCl concentration was still too low. '

(c) In the following experiments 0.01 mol a- (3> 4— Dichloroanilino) propiononitrile and 10 ml of absolute alcohol in the presence of various amounts of HGl (see table II) heated to reflux temperature until the starting material was fully implemented. The results show that if the HCl concentration is too low, an extensive Networking takes place. One heated the mixture before it was brought to the reflux temperature, to a lower one Temperature, on the other hand, very little if any, dichloroaniline (BCA) was formed.

TABLE II

Moles of HCl reflux DCA formed

(Mol%, based on hitrile)

Reflux 5 5 time in hours 4- 2, O,

0.025 4- .32

~ O, O35 * 2.5 23

0.10 0.5 10

* HCl was introduced as a gas into the boiling mixture.

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• - 22 -

Example 2.

Production of ethyl a- (N-benzoyl-3,4 - dichloroanilino) propionate . ·. .

A mixture of 263,4- g (1.005 mol) of the ethyl ester of α- (3,4-dichloroanilino) -propionic acid (prepared according to example 5 - 98.5% purity) and 100 ml of toluene was heated under reflux at 130 ⁰ O , whereupon 162 gr (1.15 mol) of benzoyl chloride were added at this temperature in the course of 45 minutes. After the mixture had been refluxed for four hours, it was cooled to 90 ⁰ C and at this temperature for 15 min with 250 ml of a 10% aqueous solution of NaHCO, stirred. After cooling, the phases were separated, the toluene layer was washed with 50 ml of water and the toluene was stripped off in vacuo (1 mm Hg); 361.2 g of ethyl α- (N-benzoyl-3,4-dichloroanilino) propionate were obtained as an oil (degree of purity 92%, yield 91.7 % of theory).

24-5 g of the crude product were dissolved by heating in 25 ml of toluene and the warm solution is poured into 500 ml of petroleum ether (bp. 60 to 8O ⁰ C). The product separated as a light gray solid which was 208.9 g, after filtration and drying in vacuo at 40 to 50 ⁰ C purified product (purity 96%) represented, which corresponds to a recovery of 89%.

PATENT CLAIMS:

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Claims (1)

PATENT CLAIMS Process for the production of alpha anilinocarbon building esters the general formula: NH-CH-X (D where R, R and R- ^ each represent a halogen atom or an alkyl, haloalkyl or alkoxy group, but R and / or R can also stand for hydrogen atoms and R a group -NH-CH (R) -X or a group - (A) _T1 -C _i H _O (R ¹ R ⁵⁾ -NH-CH (R ^4), CH = ■ -X in which A = _0, O, S or NH, and η is zero or 1; while R stands for a hydrogen atom or an alkyl group and X for a carboxylic acid ester group, characterized in that a nitrile of the general formula: (II) 2 0 9 8 4 7/1191 222: ί09 where R, R, R ^ and E have the above meaning, reacts with a primary or secondary alcohol in the presence of hydrogen chloride or hydrogen bromide, and although (a) at a temperature of -20 to + 70 ° within a time that does not exceed that which for a conversion of at least 70% of the nitrile is necessary, and then (b) at a temperature of 55 to 150 ° C, with at least during the Period of time (a) the amount of HCl or HBr present more than 3j5 equivalents, calculated on the nitrile, and the concentration of the hydrogen halide in the reaction medium is at least 4 mol per liter. 2) Method according to claim 1, characterized in that there is a starting material 1 2 nitrile is used in which in formula II R = H; R = H, Cl, F, alkyl, haloalkyl or alkoxy; R ⁵ = Cl or F; and R = H or alkyl, the alkyl, haloalkyl and alkoxy groups having no more than 6 carbon atoms. 3) Method according to claim 2, characterized in that a nitrile is used, where R ¹ = H, R ² = H or Cl5, R ⁵ = Cl or F and R ⁴ =. 4) Process according to claim 3, characterized in that a- (3) 4-dichloroanilino) propiononitrile used as starting material. 5) Method according to one of claims 1 to 4, characterized in that one. as Ilalog carbon 209847/1191 ORIGINAL INSPECTED 22? ' hydrogen halide chloride is used. 6) Method according to one of claims 1 to 5 »characterized in that as Alcohol used ethanol. 7) Method according to one of claims 1 to 6, characterized in that the Implementation carried out in the absence or at least in the substantial absence of water. 8) Method according to one of claims 1 to 7 j characterized in that the alcohol is used in excess of the required stoichiometric Amount used as a solvent or diluent. 9) Method according to one of claims 1 to 8, characterized in that within the first temperature range the reaction time is not longer than that which is necessary for a conversion of at least 90, in particular 95 to 99% of the nitrile. 10) Method according to one of claims 1 to 9 _5, characterized in that the chlorine or. Hydrogen bromide is used in an amount of 5 to 15 equivalents based on the nitrile. 11) Method according to one of claims 1 to 10, characterized in that the Chlorbzw. Hydrogen bromide is used in the reaction medium in a concentration of 6 to 10 mol per liter. 209847/1191 inspected 22? ' 12) Method according to one of claims 1 to 11, characterized in that a temperature of 30 to 65 ⁰ C is used in the first temperature range (a). 13) Method according to one of claims 1 to 12, characterized in that a temperature of 70 to 10O ⁰ C is used in the second temperature range (b). Process according to one of Claims 1 to 13, characterized in that the Reaction in succession, first at a lower temperature and then at a higher temperature, especially at the Boiling temperature. 15) Process for the preparation of an alpha (N-acylanilino) carboxylic acid ester, characterized in that one according to one of the claims 1 to 14 produced alpha aniloxnocarboxylic acid ester is reacted with an icylating agent. 16) Method according to claim 15 j, characterized in that one is used as acylating agent Benzoyl chloride used. 17) Process for the preparation of alpha anilinocarbonitriles of the above general formula II, characterized in that an aniline compound the general formula: 209847/1 191 ORIGINAL INSPECTED 22-109 (in) in an alcoholic medium with either (a) Hydrogen cyanide and an aldehyde, R-CHO or (B) a cyanohydrin, E -CH (OH) -Clf converts, with im Pail (b) a strong base is present. 18) Method according to Claim 17 »characterized in that the aniline compound used is 4-chloroaniline, 4-ITu.oraniline, 4— chloro-3-fluoroaniline, 3> -chloro-4— fluoroaniline or especially 3j4 - dichloroaniline used. 19) Method according to claim 17 or 18, characterized in that in i'all (a) as aldehyde acetaldehyde and in case (b) used as gyanohydrin alphahydroxypropiononitrile. 20) Method according to one of Atisprüche 17 to 19, characterized in that as Alcohol used ethanol. Method according to one of Claims 17 to 20, 209847/1191 i103 characterized in that both the hydrogen cyanide and the aldehyde are used in excess from 6 to 10, in particular from 4 to 7 mol%, calculated to the aniline compound. 22) Method according to one of claims 17 to 21, characterized in that. that one Aldehyde is added to a mixture of HCN and the aniline compound in the alcoholic medium. 23) Method according to one of claims 17 to 22, characterized in that the Reaction in Pail (a) at a temperature of 10 to 25 ° C. 24) Method according to one of claims 17 to 20, characterized in that the Cyanohydrin in an excess of 10 to 50, especially from 20 to 40 mol%, calculated on the aniline compound, used. 25) Method according to one of claims 17 to 20 and 24, characterized in that that a tertiary nitrogen base is used as the base in case (b). 26) Method according to claim 25 »characterized in that the tertiary amine is triethylamine used. 27) Method according to claim 25 or 26, characterized in that - 2 0 9 8 4 7/1191 ORIGINAL INSPECTED indicates that one is the tertiary nitrogen base in an amount of 0.3 "to 10 mol% on the cyanohydrin. 28) Process according to one of claims 17 to 20 and 24 to 27, characterized in that the reaction in case (b) is carried out at a temperature from 50 to 100, in particular from 60 to 80 ^° C. 29) Method according to claim 28, characterized in that the reaction is carried out in ethanol carried out at the boiling point of the reaction mixture. 30) a- (fluoroanilino) and a- (chlorofluoroanilino) propiononitrile. 31) α- (4-fluoroanilino) propiononitrile. 32) α- (4-Chloro-3-fluoroanilino) propiononitrile. 33) Process for the preparation of alpha anilinocarboxylic acid esters and / or their N-acyl derivatives, thereby characterized in that an aniline compound of the general formula III with either (a) HCW and an aldehyde, R ^ -CHO or (b) a cyanohydrin, R-CH (OH) -CN, to one Reacts nitrile of the general formula II, which is then converted into a Carboxylic acid ester of the general formula I is converted, whereupon this ester optionally by Acylation converted into the corresponding N-acyl derivative. 20 9847/1191 109 34 ·) Method according to claim 33, characterized in that a Mtril (II) is used, which is produced with the aid of the method according to one of claims 17 to 29- 35) Method according to claim 33 or 34 · » characterized in that the conversion of the nitrile (II) into the carboxylic acid ester (I) is carried out with the aid of the method according to one of claims 1 to 14 and for the conversion of the ester (I ) a method according to claim 15 or 16 applies in the N-acyl derivative. 209847/1191 ORlGiNAL INSPECTED