DE1643896B2 - Process for the production of alpha-hydroxy-gamma-methylmercaptobutyramide - Google Patents

Description

It is known, α-hydroxy-γ-methylmercapto-butyramide by hydration of α-hydroxy-γ-methylmercaplo-butyronitrile to be prepared with aqueous sulfuric acid. u-hydroxy-y-methyl mercapto-butyramide shows methionine or methionine as an additive in feed mixes for poultry rearing the calcium salt of a-hydroxy-y-methylmercapto-butyric acid Corresponding growth-stimulating effect with a suitable compound composition the effectiveness of methionine and methionine-hydroxy-analog calcium salt can surpass (U.S. Patent 2,745,745).

A disadvantage of the previously known process for the preparation of -hydroxy-γ-methylmercapto-butyramide is that the sulfuric acid used for hydration is insoluble, calcium sulfate that is difficult to filter is deposited and the contaminated mother liquor amide via an organic Solvent must also be cleaned.

u-Hydroxy-y-methylmercapto-butyramid has no ♦ » gained greater importance, since it has so far only been produced with average yields of around 70% could be (US Pat. No. 2,938,953), while the yields in the manufacture of methionine over 80% and from α-hydroxy-γ-methyl mercaptobutyric acid Calcium are 90%.

According to the process according to the invention, provided that water is used as the diluent, and neutralization with ammonia carries out, with yields of 88 to 90% an 80 to 90% 5 <> Product that contains approximately 17 to 20% ammonium sulfate, by direct crystallization of the amide from the aqueous solution.

A single recrystallization from water leads to a 98-99% α-hydroxy-γ-methylmercapto-butyramide. Since the amide is sensitive to hydrolysis, it is advisable to use gentle recrystallization Conditions to be observed and temperatures in excess of 75 ° C to be avoided. The connection is advantageously dried in a vacuum.

According to a variant of the process according to the invention, organic substances which can be tinned with water can be used Solvents such as methanol, ethanol, isopropanol, acetone, acetonitrile, tetrahydrofuran and dioxane as Diluents can be used. Methanol and acetonitrile are preferred. In this case the Neutralization with 100% gaseous or liquid ammonia.

The procedure is that both the dilution of the a -hydroxy- γ -methylmercapto-butyramide-sulfuric acid mixture with the organic solvent and the neutralization of the sulfuric acid with ammonia are carried out at temperatures below about 75.degree.

The filtration of the insoluble ammonium sulfate is carried out at elevated temperature, ~ ve gsweise between about 55 and about 70 ⁰ C. After, cooling the filtrate deposited a-hydroxy-y-methylmercaptobutyramid in the form of colorless leaflets from the solution

In order to avoid solvent loss, it is advisable to use organic solvents It is advisable to circulate the mother liquor as a diluent and to add it to the next batch.

According to this procedure, α-hydroxy-γ-methyl mercapto-butyramide is obtained with about 90% yield and with a degree of purity of 90 to 94% without additional Cleaning operation received.

By recrystallizing the α-hydroxy-γ-methylmercapto-butyramide obtained in the manner described from water or an organic solvent such as methanol, ethanol and acetonitrile a quality of over 99% can be produced.

example 1

104 g / ϊ-methylmercapto-propionaldehyde (100%) with 43 ml of 98% hydrogen cyanide at 20 to 25 "C in the presence of trimethylamine as a catalyst converted to a-hydroxy-y-methylmercapto-butyr ^ nitrile.

A mixture of 56 g of concentrated sulfuric acid is then left with vigorous stirring while cooling and 16.5 g of water at 25 to 35 C to the α-hydroxy-γ-methylmerciipto-butyronitrile to drip. After the addition has ended, the reaction mixture is kept at 35 to 45 ° C. for a further 2 hours. One dilutes while cooling with 50 ml of water and neutralizes the sulfuric acid present with concentrated aqueous ammonia.

After cooling to 5 to 20 ^° C., the very viscous crystal slurry is well suctioned off. Drying in vacuo at 60 ° C. gives 164 g of a-hydroxy-y-methylmercaptobutyramide / ammonium sulfate mixture, the amide content of which is 81.5%, which gives a yield of 133.5 g of a-hydroxy-y-methylmercapto-butyramide (89, 5% of theory, based on / J-methyl mercaptopropionaldehyde).

Example 2

104 g / i-methylmercapto-propionaldehyde (10%) and 43 ml of 98% hydrogen cyanide are, as described in Example 1, first to give α-hydroxy-j'-methylmercapto-butyronitrile reacted and then hydrated by a mixture of 56 g of concentrated sulfuric acid and 16.5 g of water. Man diluted while cooling at 20 to 25 ° C with 150 ml of water and neutralized the sulfuric acid with concentrated aqueous ammonia to ammonium sulfate.

The mixture is then heated to about 65 ° C. with the addition of a further 50 ml of water, clarified with 1% activated charcoal, filtered while hot and the filtrate is cooled to ^{0 ° C.} A-hydroxy-y-methylmercapto-butyramide crystallizes out in shiny flakes. After vacuum drying at 6O ⁰ C is obtained 132 e a-Hvdroxv-v-

methylmercapto - butyramide / ammonium - sulfate - Ge methanol instead of acetonitrile and the Neutrahmisch, what at an amide content of 92.2% 121.5 g of ionization with 100% ammonia at 25 ° C vorgenoma-hydroxy-y-methylmercapto-butyramide (81.5% of the men. After separation of the ammonium theory, based on / I-methyl mercapto-propional sulfate at 55 ° C., washing with 100 ml of methanol dehydration). 5 and cooling to about 5 ° C, a-hydroxy-y-methyl-

. mercapto-butyramide in fine flakes with over 90%

Example 3 content isolated. The resulting mother liquor (approx

The from 104 g / J-methylmercapto-propionaldehyde 250 ml) is used to dilute the following batch

(100%) which can be produced according to the information in Example 1 are used.

α-Hydroxy -) '- methylmercapto-butyramide-sulfur- «> In this way of working, you get on average

acid mixture is after four hours after 143.5 g of a-hydroxy-y-methylmercapto-butyramide / Am-

reaction at 35 to 45 ° C with 500 ml of acetonitrile ammonium sulfate mixture with 93.5% amide content, what

thins. After neutralization of the sulfur present, an amount of 134 g of a-hydroxy-y-methylmercapto-

Acid heated by 100% ammonia at 20 ⁰ C corresponds to butyramide (100%). The yield is

one to 70 ⁰ C and removes insoluble ammonium 15 accordingly 90%, based on / ϊ-MethyImercapto-pro

sulfate by filtration. From the pionaldehyde by rewashing.

The filtrate obtained with 100 ml of acetonitrile crystallizes _n . .

on cooling to 10 ⁰ C a-hydroxy-y-methy.'mer- Example 5

capto-butyramid in fine flakes and can contain 143.5 g of a-hydroxy-y-methylmercapto-butyramid /

be isolated by suction. »° Ammonium sulfate mixture prepared according to Example 4

The resulting mother liquor has a low amide content of 9?, 5%, corresponding to an amount

docile addition of fresh acetonitrile to a total of 134 g of a-hydroxy-y-methylmercapto ^ butyramid

volume of 600 ml and diluted 100%, are in 110 ml of water (preheated to 60

a following approach was used. At this to 65 ° C) dissolved and then to 0 to overnight

Working method, an average of 145 gahydroxy-> 5 - 2 " C are cooled. After suctioning off, in a vacuum at

γ- methylmercapto-butyramide / ammonium sulfate-Ge 55 ° C dried. This gives 122 g of a-hydroxy

obtained mixed with an amide content of 91%, which y-methylmercapto-butyramide with a content of

an amount of 132 g of a-hydroxy-y-methylmercapto- 99.2%, corresponding to 121 g of 100% amide ..

butyramid (100%). The yield is based on ß- methylmercapto-propionaldehyde,

accordingly 88.5%, based on β- methylmercapto-pro-30, the yield is 81%.

pionaldehyde. From the aqueous mother liquor, after a

tight in a vacuum (25 to 30 ⁰ Q another 5 g of a

Example 4 a-Hydroxy-y-methylmercapto-butyramide / ammonium

The procedure is as described in Example 3, sulfate mixture with 90% amide content is isolated,

however, the dilution of the a-Hyriroxy-y-methylmer- 35 so that the total yield of amide is 84%

capto-butyramid-sulfuric acid mixture increased by 200 ml.

Claims (2)

Patent claims: 1. Process for the production of a-Hydroxy-ymethylmercaptobutyramide from those used in the hydration of α-hydroxy-γ-methylmercapto-butyroniitrile with aqueous sulfuric acid resulting mixtures by dilution, neutralization of the Acid and cooling, characterized that one carries out the neutralization with ammonia. 2. The method according to claim 1, characterized in that when using one with Water-miscible organic solvent as a dilution with gaseous or liquid ammonia neutralized.