DE2014801A1 - Process for the preparation of malononitrile derivatives - Google Patents

Description

"Process for the production of malononitrile derivatives" Priority: March 28, 1969, Japan, No: 24081/69.

It is known from Alkoxymethyleniiialonsäuredinitril- or Dialkylaminomethylene malononitrile compounds through Reaction with amidine compounds 2-methyl-4-aminö-5-cyanopyrimidine to manufacture; cf. z. B. British Patent 1,087,505. The 2-methyl-4-amino-5-cyanopyrimidine is a important intermediate for the production of ihiamines.

Äthoxymethylenmalonsäuredinitril z. B. has so far been through Implementation of triethoxymethane, d. H. Ethyl orthoformate, with malononitrile and acetic anhydride and subsequent separation of the product from the reaction mixture produced by distillation or extraction * This one

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Process not only has the disadvantage that ethyl orthoformate is an expensive compound, but that the separation of the reaction product is also "expensive.

Dimethylaminomethylene malonic acid dinitrile, for example, has previously been used by Implementation of Ν, Ν-dimethylformamide-di thylacetal with malononitrile manufactured; See H. Meerwein et al., Liebigs Annalen der Chemie, Volume 64-1, page 1 (1961). This procedure too is uneconomical because of the expensive starting compounds.

The object of the invention was therefore to create a new, simpler and cheaper process for the preparation of malononitrile derivatives of the aforementioned type. This object is achieved by the invention.

The invention thus relates to a process for the preparation of malonic acid nitrate derivatives of the general formula I.

E-CH = C-CN (I)

in which R is an alkoxy group, such as a methoxy, ethoxy, propoxy or butox ^ group, or a dialkylamino group, such as the dimethylamino or diethylamino group, and X is a cyano group or a carbalkoxy group, such as the carbomethoxy or carbethoxy group , means. The procedure is characterized by

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net that one

(a) for the preparation of the compounds in which R is a dialkylamino radical means either initially a dialkylformamide with an alkyl chloroformate under exclusion of water and in the cold, then the A tertiary amine is added to the reaction mixture in the cold, followed by the basic reaction mixture in the cold with a gyanomethylene compound of the general Formula II

CH ₂ -CN. (II)

X

in which X has the above meaning, added and ^{heated to temperatures of about 30 to 40 °} C., or the components are reacted at the same time in the presence of the tertiary amine, initially in the cold and then at about 30 to 40 ^° C., and that one

Cb) for the preparation of the compounds in which R is an alkoxy radical, either first the dialkylformamide is reacted with the alkyl chloroformate with exclusion of water in the cold and then the reaction mixture is treated with the cyanomethylene compound in the cold and the mixture is brought to temperatures of about 30 to 40 ⁰ C heated or

the components first in the cold and then approximately

at ^ 30 to 40 ° C at the same time to implement and optionally a tertiary amine is then added to the reaction mixture.

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Preferably used in the process of the invention as dialkylformamide Dimethylformamide, as alkyl chloroformate ethyl chloroformate and either malononitrile or ethyl cyanoacetate is used as the cyanomethylene compound. The Um-

Settlement is preferably done in one under the reaction conditions inert, anhydrous solvent 'carried out. Examples Solvents that can be used are hydrocarbon solvents such as aliphatic, cycloaliphatic and aromatic Hydrocarbon solvents. The preferred solvent is benzene.

For the preparation of the compounds in which R is a dialkylamino radical means, the reaction of the cyanomethylene compound of the general formula II in the presence of a tertiary amine carried out. Examples of tertiary amines that can be used are trialkylamines, such as trimethylamine, triethylamine and tripropylamine. Triethylamine is preferred.

The method of the invention using the example of the implementation of dimethylformamide with ethyl chloroformate and the cyanoethylene compound of the general formula II can be reaction mechanistic can be explained as follows:

CH
CH,

0
N-CH

CH CH

CH

OCOOC ₂ H ₅

OC ₂ H ₅

Cl '

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GN CH +

CH

(Ill)

N-CH = C ^ + C ₂ H ₅ OH ^ X

Cleaves from the intermediate of the general formula III dimethylamine from (reaction path a) when the cyanine ethylene compound the general formula. II is added to the reaction mixture of dimethylformamide and ethyl chloroformate in the absence of the tertiary amine. In the presence of the tertiary amine, reaction path b) is taken, and it splits up from the intermediate of the general formula III Ethanol off.

The method of the invention has a further advantage which is of particular technical importance. After completion of the implementation chloroformic acid alkyl ester that has not yet reacted may be present in the reaction mixture, which easily dissolves Cleavage into the corresponding alkyl chloride and carbon dioxide decompose, lets; see Angew. Chem., Vol. 72, pp. 8-6 (1960). The reaction mixture can thus be subjected directly to a subsequent further reaction without the product having to isolate. - ■

The examples illustrate the invention.

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example 1

19 S dimethylformamide are introduced into 23.6 g of ethyl chloroformate with ice cooling and with exclusion of water. The mixture is stirred for> 0 minutes in the cold, then 3.6 g of malononitrile are added while cooling with ice, and the mixture is stirred for 1 hour while cooling with ice. The reaction mixture obtained is heated for 1 hour on tree temperature and then 2 1/2 hours at 35 ⁰ C. When the reaction has ended, dimethylamine hydrochloride crystallizes out. The solution is then cooled and poured into cold water. This causes crystals to separate out. The aqueous mixture is extracted with benzene, the benzene extract is washed with water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. 5.19 g of crude ethoxymethylene malononitrile remain. The yield is 80% of theory. After recrystallization from ethanol or a mixture of ether and cyclohexane, colorless prisms with a P. 67 ° C are obtained. The IR and UV absorption spectrum is identical to that of an authentic sample.

Example 2

40 ml of anhydrous benzene, 7.31 S dimethylformamide, 10.85 S ethyl chloroformate and 1.65 g malononitrile are used ^; brought the according to Example 1 to implementation. The reaction is carried out for 6 hours until crystalline dimethylamine hydrochloride separates out. The dimethylamine hydrochloride is removed from the reaction mixture by extraction with water. There-

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after the benzene solution is worked up according to Example 1. Yield 3.05 g (85.3% of theory) ethoxymethylennalonic acid dinitrile.

Example 3

21.7 β dimethylformamide, 21.7 g of ethyl chloroformate and 5.66 g of ethyl cyanoacetate are reacted according to Example 1. Thereafter, 21.7 6 triethylamine is added dropwise to the reaction mixture over a period of 2 hours, while cooling with ice and stirring. When the addition is complete, the mixture is heated to room temperature for 1 hour and then to 35 ° C. for 2 1/2 hours. The reaction mixture is worked up as in Example 1. 9.12 g of brownish crystals of ethyl ethoxymethylene cyanoacetate are obtained. After recrystallization from a mixture of ether and cyclohexane, the colorless needles melt at 50 to 51 ^° C. Yield 4 g (50% of theory). The IR and UV absorption spectrum of this compound is identical to that of an authentic sample. ·

Example 4 ^

21.7 g of dimethylformamide are mixed with 21.7 g of ethyl chloroformate while stirring with ice and reacted for 30 minutes in the cold. Thereafter, the mixture is added dropwise at 0 to 5 ° C with 21.7 g of triethylamine and then also in the cold within 2 hours with 3.3. g of malononitrile "are added. The reaction mixture is then warmed to room temperature for 1 hour and then to 35 ° C. for 2 1/2 hours.

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Working up is carried out as in Example 1. One obtains eir. dark brownish oil. The product becomes more neutral. Alu-ir.iuaoxyd chromatographed and eluted with benzene. After the vaporization of the eluate, pale yellow flakes are obtained. SS to "87 ⁰ C. Yield 0.6 g (10% of theory). The IR ur.d UV absorption spectrum of this compound is with an authentic sample (Liebigs Annalen der Chemie, Volume 641 (1961), page 1 to 39> Angew. Chem., Volume 72 (1960), page 77) are identical.

Example 5

6 21.7 dimethylformamide, ethyl chloroformate 21.7 S, 21.7 g of triethylamine and 5.66 g Cyanessigsaureathylester are mixed in the manner described in Example 4 with each other and reacted. The work-up is carried out in the same way. A greenish brown crystalline residue obtained after evaporation of the Benzollösune · Recrystallization of the crude product from diethyl ether pale yellowish white needles of 80 F. are obtained to 81 ⁰ C. Yield 2.61 g (31 % of theory). The IR and UV absorption spectrum is identical to that of an authentic sample; Ancew. Chem., Vol. 72, p. 77 (1960).

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Claims (4)

P a tentan application before 1y Process for the preparation of malononitrile derivatives of the general formula I. R-CH = C-CN (I) ι ' in which R is an alkoxy group or a dialkylamino radical and X represents a cyano group or a carbalkoxy, characterized -ä in that (a) for the preparation of the compounds in which R is a dialkylamino radical means either first a dialkylformamide with an alkyl chloroformate under Exclusion of water and reacted in the cold, then the reaction mixture in the cold with a tertiary amine added and then the basic reaction mixture in the cold with a cyanomethylene compound of the general Formula II CH ₂ -CN. (II) X · .- ■ ■ -. ■ in which X has the above meaning, are added and to 4O ⁰ C heated to temperatures of about 30 or the components simultaneously in the presence of the tertiary amine, first in the cold and then JO brings to react at about ⁰ C to 4-0, and that 009841/1938 20H801 (b) To prepare the compounds in which R is an alkoxy radical, either the dialkylformamide is first reacted with the alkyl chloraneisate in the cold with exclusion of water and the cyanomethylene compound is then added to the reaction mixture in the cold and the mixture is heated to temperatures of about 50 to 40 ° C heated or the components initially in the cold and then J> 0 to 4O ⁰ C brings about the same time to implement, and optionally then added to the reaction mixture with a tertiary amine. 2. The method according to claim 1, characterized in that one as dialkylformamide, dimethylformamide, as alkyl chloroformate Ethyl chloroformate and, as the cyanomethylene compound, malononitrile or ethyl cyanoacetate used. 3. The method according to claim 1 and 2, characterized in that the reaction is carried out in an inert anhydrous solvent, preferably in benzene. 4. The method according to claim 1 to 3 »characterized, that the tertiary amine is a trialkylamine, preferably tri-> ethylamine, is used. 009841/1938