NO170578B - PROCEDURE FOR PREPARING N, N-DIMETHYLAMINOMETHYLARYL COMPOUNDS - Google Patents

Description

Procedure for extracting kawain or methysticin from the reaction mixture obtained by reaction of Y-bromo-B-methoxy-crotonic acid alkyl esters with cinnamic acid aldehyde resp. methylenedioxy-cinnamaldehyde in the presence of zinc.

The invention relates to a method for extracting kawain or methysticin from the reaction mixture obtained by reaction of Y-thirom-$-methoxy-crotonic acid alkyl esters with cinnamic acid aldehyde, resp. methylenedioxycinnamic acid aldehyde in the presence of zinc. Such methods are known (for comparison with respect to synthetic kawain Kostermann's (Recueil 70 (1951) 79-82) or synthetic methisticin US patent no. 2,870,164). In these methods, the condensation with zinc proceeds as a normal addition of organometallic compounds to carbonyl groups in ether, benzene, toluene, tetrahydrofuran and other inert solvents.

According to these proposals, zinc is first made oxide-free, with dilute hydrochloric acid, washed with water-methanol-acetone-ether, dried at 100°C and then activated with iodine. The reaction components are then added to the pre-purified and activated zinc. After completion of the reaction, in both cases the condensation mixture is shaken with saturated ammonium chloride solution and extracted several times with ether or chloroform.

Kawain or methysticin as well as organic pollutants

passes into the extractant. The yields from these methods are so small - with Kosterman's method only 16.7% kawain is obtained, referred to the cinnamaldehyde used - that they are not technically applicable. These low yields are attributable to the fact that the zinc bromide formed in the reaction cannot be completely separated because it has a negative effect on the yield when the extractant evaporates.

This disadvantage is avoided according to the invention/by; and a manufacturing release method with high yields is provided (e.g. 90%, resp. 96.3%) by introducing the reaction mixture while stirring as a thin stream into a 5-115% mineral acid, preferably an aqueous dilute hydrochloric acid solution.

Thereby. falls kawain. resp. methysticin right away

and in a high percentage and degree of purity without the addition of an extractant.

According to a preferred embodiment according to the invention, the reaction mixture is cooled before introduction to 40-45°C.

The mineral acid solution's concentration must not exceed 1155., while concentrations of less than 5% delay the precipitation of the reaction product.,

It is known for reaction products according to the Reformatzki reaction to use diluted mineral acid instead of ammonium chloride solution for the cleavage of the zinc salt. For example, such a method has been used with a 6-halogencrotonic acid ester after reaction with cinnamaldehyde. However, when using this method with a methoxycrotonic acid ester reaction product, i.e. a reaction product with pyrone ring formation, the use of such a diluted mineral acid was not close. On the contrary, it was remote because the OCH^ group in a halogen-methoxycrotonic acid ester is exceedingly sensitive, and the cleavage of the pyrone ring already occurs at very low acid concentrations at ordinary temperature upon standing.

Surprisingly, no saponification or

cleavage of the pyrone ring when the reaction product including the organic solvent is introduced in a thin stream with stirring into the dilute acid solution.

The invention shall be explained in more detail by means of

some examples.

Example 1. x-

1000 g of cinnamaldehyde and 1700 g of ethyl-Y-bromo-8-methoxycrotonate are mixed with 2500 ml of benzene, toluene, tetrahydrofuran or another inert solvent and slowly poured onto zinc. After initial heating, the reaction proceeds without heat input. After one hour, the mixture is kept for a further 2 hours at 80°C.

It is then allowed to cool to 40-45°C and, with constant movement, sucks the whole in a thin stream into a 10/S-ig HCl solution. The caffeine falls out spontaneously.

After two washes, the zinc salt is completely removed. Thus, 1120 g of raw kawain and after recrystallization 900 g of renkawain were obtained, which corresponds to a yield of 90%, referred to cinnamaldehyde.

Example 2.

500 g of methylenedioxy-cinnaldehyde and 640 g of ethyl-Y-bromo-3-methoxycrotonate are mixed with 2000 ml of benzene, toluene, tetrahydrofuran or another inert solvent and slowly poured over zinc. After initial heating, the reaction proceeds without heat input. After 1 hour, the mixture is kept for a further 2 hours at 80°C. It is then allowed to cool to 40-45°C and, while constantly moving, sucks the whole in a thin stream into a 10# aqueous HCl solution. The methylsticine precipitates at once with a light brown color. After two washes, the zinc salt is completely removed.

604 g of crude methysticin and after recrystallization 482 g of pure methysticin are obtained, which corresponds to a yield of $96.4, referred to methylenedioxycinnamaldehyde. Temp. at 134°C.

Claims (2)

1. 'Procedure for extraction of kawain resp. methysticin from the reaction mixture obtained by reacting ybromo-B-methoxy-croton alkyl esters with cinnamic aldehyde resp. methylenedioxycinnaldehyde in the presence of zinc and an inert organic solvent and cleavage of the zinc salts to release kawain resp. methysticin, characterized in that the cleavage is carried out by introducing the reaction mixture in a thin stream while stirring in a 5-1/2 mineral acid, preferably hydrochloric acid, with precipitation of kawain or methysticin. 2. Method according to claim 1, characterized in that the reaction mixture, after cooling to between 40 and 45°C, is introduced into an approx. 10% hydrochloric acid solution.