DE1166201B - Pressureless process for the preparation of hydantoins which are mono- or disubstituted in the 5-position - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

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£ 116 L201

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Boarding school Class: C07d

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German class: 12p-9

D 30432 IVd / 12 ρ
April 15, 1959
March 26, 1964

As is known, hydantoins can easily be recrystallized from water or organic solvents. They can therefore be isolated well in pure form and with advantage as a preliminary stage in the production of Amino acids are used. Numerous processes have been described for the production of the hydantoins been. For example, it is known to produce C-substituted hydantoins industrially from aldehydes or to produce ketones, alkali cyanides and ammonium carbonate. Equivalent Quantities in an autoclave at a pressure of 2 to 10 atmospheres and a reaction time of 2 to 4 hours and a temperature of about 80 ° C are implemented. The yields of these processes are very high. To separate the hydantoin from the reaction mixture, it is necessary to remove the excess To neutralize alkali with acid (cf. Chemical Reviews, Vol. 46 [1950], pp. 422 to 425, and German patent specification 566 094).

It is also known to carry out the above synthesis under normal pressure. But here must with an excess of ammonium salts of carbonic acid, such as ammonium carbonate, ammonium bicarbonate and ammonium carbonate, because otherwise a sufficient temperature at temperatures below 60 ° C Hydantoin formation does not take place. In general, 2 to 5 molar excesses are used (see Journal für Praktische Chemie [2], Vol. 140, [1934], pp. 291 to 316; Houben-Weyl: Methods of organic chemistry, Vol. 11/1, 4th edition [1957], pp. 185 and 186).

It is also known in these processes for the preparation of hydantoins instead of ketones and alkali cyanides to use the corresponding cyanohydrins as starting materials. It will, however extremely poor yields were obtained here (cf. Journal für Praktische Chemie [2], Vol. 141 [1934], pp. 5 to 43). Even with the reaction of acetone cyanohydrin with ammonium carbonate in an equimolecular manner The ratio to dimethylhydantoin could, as has been shown, even with a reaction time a yield greater than 48.7% cannot be achieved within 3 days.

US Pat. No. 2,391,799 also describes a process for the production of hydantoins, according to which a mixture of aldehydes or ketones with free liquid hydrocyanic acid is reacted with aqueous ammonium carbonate. Although the yields of this process are high, it can only do so under normal pressure with certain difficulties, which are greater due to the outgassing Amounts of hydrogen cyanide with carbon dioxide conditional

Pressureless process for the production of
monosubstituted or disubstituted in the 5-position
Hydantoins

Applicant:

German gold and silver separator
formerly Roessler, Frankfurt / M., Weißfrauenstr. 9

Named as inventor:
Dipl.-Chem. Dr. Ludwig Guardian,
Ulrich Reichau, Frankfurt / M.,
Dipl.-Chem. Dr. Erich Liebetanz, Mainz

are to be carried out technically. Working under pressure can handle the dangers associated with the Avoid outgassing of hydrogen cyanide. However, it will be used for molar sales Response times of up to 104 hours are required.

In all known processes carried out with an excess of ammonium carbonate the corresponding excess carbonic acid must be drained off. It must be Particularly in the case of larger batches, increased outgassing can be expected. Escape here volatile starting materials from the liquid reaction medium. Do you want a gas scrubber and that Avoid using adsorption towers to recover them, so there must be considerable substance losses of reaction participants are accepted. The consequences of this are lower yields as well as nuisance to the environment by escaping hydrogen cyanide.

To isolate the resulting hydantoins from the alkaline reaction solutions and from the Since then, the mother liquor has had to completely remove the excess ammonium salts by boiling them Solution to be removed. In addition, it was necessary to convert the remaining alkalis with acid in foreign salts convict.

The invention now relates to a pressureless process for the production of hydantoins, which in 5-position are monosubstituted or disubstituted, from aldehydes or ketones and hydrocyanic acid or from the corresponding cyanohydrins by reaction with ammonia and carbon dioxide in the presence excess amounts of ammonia and in the presence of water or organic solvents

409 540/540

3 4

Temperatures below 60 ° C, at which one in a timely about 24 1 carbon dioxide over a dry presented Solution of 5 to 100 moles of ammonia introduced into gas meter. The temperature is reduced by cooling than 5 moles of water, which may be kept between 45 and 55 ° C as a treatment. To Solubilizer in addition still methanol or a further 30 minutes and after cooling on May contain ethanol, at the same time every 1 mole of carbon 5 30 ° C begins to precipitate the crystalline hydantoin, Dioxide and aldehyde or ketone cyanohydrin or It is suction filtered, washed and dried. the instead of the cyanohydrin slowly per 1 mol of blue yield is 61.7%. The mother liquor is in acid and aldehyde or ketone enters. Evaporated in a vacuum. While recovering the If you place a saturated ammonia-ammonia excess, a further 33.4% hyaline solution is added before. io dantoin with a melting point of 175 ° C

To avoid the formation of by-products.

The best way to work below 60 ° C is b) The procedure is as described under a),

a temperature between 25 and 55 ° C. However, the mother liquor is

preferably used again in the presence of about 2.5 moles of water separation of the hydantoin. That

worked. This ensures that ammonia consumed during 15 is in the form of a 25% strength

the reaction replaced crystalline or oily aqueous ammonia solution. Another mole

Products can be obtained. Acetone cyanohydrin is used within 30 minutes

The process according to the invention can also be added and in turn carried out continuously for about 24 to 25 liters. Carbon dioxide is advantageously gassed in. The first excretion of adhesively worked in the circuit and the product 20 solid dimethylhydantoin amounts to 124 g (= 97% over a separating container already during the theory).
Implementation from the cycle continuously or periodically
removed. Depending on the degree of purity and the water solubility of the starting materials used, this falls into the same apparatus as in Example 1 in the normal case in crystalline or in particular at 25, 200 g of 25% aqueous ammonia solution using solvents in oily or initially introduced. A dropping funnel turns into dissolved form within. The latter two cases occur less frequently after a reaction time of 40 minutes. A work-up of the mother liquor from 1.5 mol of pure, freshly distilled hydrocyanic acid lye is only slowly necessary in this case of product isolation in (= 40.5 g) and 1.5 mol of acetone (= 87 g) as it is in order to eliminate the ent- 30 added with stirring. At the same time, about 36 liters of carbon dioxide are added over a standing amount of 1 mol of water with a molar dry gas meter in order to maintain normal water levels. The temperature is kept from 2.5 to 10 mol in the reaction solution at about 35 ° C. by cooling. In a vacuum one acts. The salty mother liquor must then be added for every mole of the resulting and isolated hydantoin in accordance with the reaction. 183 g of dimethylhydantoin with a melting point of 175 ° C. are taken from the isolated hydantoin saturated reaction solution. In general, this is 95.2% of theory.
2 to 5% of the total approach. The type of iso-. .
The distribution of the reaction products is also largely 40 Example 3
As in Example 1, 200 g of 25% strength aqueous are dependent on the solubility of the hydantoins formed. For example, if ammonia solution is present, about 40 g of methanol of readily soluble ammonium hydantoate can be added as a solvent. From a drip, the products in dissolved form the circuit funnel will be removed within about 45 minutes under and separately to isolate a mixture of 2 mol of methyl ethyl ketone excess solvent by evaporating the 45 stirring. Here (= 144 g) and 2MoI hydrocyanic acid (= 54 g) are added dropwise, the solvents and the ammonia can be recovered. The temperature will be. Maintained at about 40 ° C. by cooling according to the process according to the invention. Even when the hydantoins are often crystalline with sharp cooling, fine white crystals precipitate. Obtained by the melting point. As a result of the mild reac- evaporation in vacuo, a light aqueous ionization conditions and the rapid product release of methanol, ammonia, hydrocyanic acid and separation takes place even when using methyl ethyl ketone. The total free hydrocyanic acid practically no formation of minor amounts of the isolated, pure white, finely crystalline products instead. Furthermore, since none of the methylethylhydantoin with a melting point of 148 ° C. 242 g of components are used in excess, none (= 84.0% of theory).
Exhaust gases on. . .

The following examples serve to illustrate example 4

the invention. As in Example 1, 200 g of 25% aqueous

60 ammonia solution and 50 g of ethanol were submitted. the end

Example 1 a dropping funnel becomes 1 mole in about 30 minutes

(== 131 g) raw, unpurified y-methyl mercapto-

a) Dripped into a 500 ml three-necked flask with stick- / J-oxybutyronitrile. At the same time is over

thermometer, reflux condenser and gas inlet - a dry gas meter 241 carbon dioxide introduced,

200 g of 25% strength aqueous ammonia are used. The temperature is 45 to 50 ° C

solution presented. A drip funnel becomes a. After about half of the cyanohydrin has been added

where 1 mole (= 85.4 g) is set within 30 minutes, two layers are formed. After loading

99.5% acetone cyanohydrin is added dropwise and, at the same time, the oily layer in the vagina is

funnel separated and the aqueous layer evaporated in vacuo. Thereupon 162 g Pale yellow colored, crystalline 5,2'-methylmercaptoethylhydantoin with a melting point of 103 ° C. is isolated. This corresponds to a yield of 93.1%, based on the cyanohydrin used.

Example 5

As in Example 1, 180 g of 25% aqueous ammonia solution and 90 g of methanol are initially charged. the end 2 mol (= 287.5 g) of 99.5% benzaldehyde cyanohydrin are added dropwise to a dropping funnel in about 45 minutes with stirring. At the same time, about 481 (= 2 mol) of carbon dioxide are released through a dry gas meter initiated. The temperature is about 50 ° C. After the methanol has been driven off in the The 5-phenylhydantoin is flaky and orange-yellow in a vacuum. It solidifies into a waxy one Dimensions. After evaporation of the mother liquor and subsequent purification, 292 g of crystalline material are obtained Crude product with a melting point of 169 ° C, corresponding to 82% of theory.

Example 6

In an apparatus that is suitable for working in the circuit and through the accompanying drawing is illustrated, 2500 g of 25% aqueous ammonia (= 36.5 mol) are introduced. Above the dosing tank 1 with the pressure equalization 2 and the drain cock 3 are either one per hour Mixture of 30 moles of acetone (= 1740 g) and 30 moles of hydrocyanic acid (= 810 g) or 30 moles (= 2562 g) of one finished 99.5% acetone cyanohydrin was added. At the same time, the Valve 13 and inlet port 12 in the centrifugal pump pit 30 mol of carbon dioxide (1320 g = 7201) introduced per hour. From a supply of liquefied Ammonia is fed via a piston metering pump through the valve 17 via the supply line and Nozzle 16 at the same time 30MoI (= 510g) ammonia fed in. By means of the pump 11, the circuit via the cooler 4, the valve 5, the Dip tube 6, the product separator 7 and the valve 10 are maintained. The nozzle 14 is used for pressure equalization. 15 is a cooling device, for example a cold finger, which is used to remove ammonium bicarbonate, which can form in the event of an overdose of carbon dioxide.

Approximately 3600 g (= 93.6% of theory) of crystalline dimethylhydantoin can be produced per hour with slight fluctuations (Melting point = 175 ° C.) can be withdrawn via product withdrawal 9 and 8, respectively. About 600 ml This results in mother liquor that is worked up separately and amounts to a total of about 200 to 240 g (= 5.3 to 6.4% of theory) Dimethylhydantoin additionally result.

Example 7

2500 g of 25% strength aqueous ammonia are placed in a circulation apparatus as described in Example 6 (= 36.5 mol) filled in. According to the above procedure, per hour over the Dosing container a mixture of 2040 g /? - methyl mercaptopropionaldehyde (20 mol) and 540 g of pure, freshly distilled hydrocyanic acid (20 mol) were added. At the same time, 20 moles (= 880 g = 480 1) Carbon dioxide introduced per hour. A piston metering pump is used at the same pace 20 mol of liquid ammonia (= 340 g per hour) fed. From the separator can per hour about 3150 g (= 90.5% of theory) of crude 5,2'-methylmercaptoethylhydantoin which separates out as an oil subtracted from. The oil slowly crystallizes out to a light yellow mass. The melting point of the The crude product is at 90 to 105 ° C. About 460 to 500 ml of aqueous mother liquor are produced per hour taken from the circuit from the separator, from which another 225 to 295 g of the hydantoin (corresponding to an additional 6.5 to 8.5% of theory) can be obtained by vacuum evaporation.

Example 8

2000 g of 10% strength aqueous ammonia are introduced into the circulation apparatus described in Example 6 filled. A mixture of 312 g / 7-methylmercapto-propionaldehyde is dispensed from the dosing tank and 89 g of hydrocyanic acid were added. At the same time 3 moles of carbon dioxide are introduced. The concentration the ammonia is kept at 8 to 10% by feeding ammonia. The temperature of the circulating solution is regulated to about 55 ° C. An approximately 30% solution of 5,2'-methylmercaptoethylhydantoin, which increases immediately after expelling the excess ammonia for example methionine can be further processed by saponification. You isolate from this If the hydantoin is dissolved, a yield of 477 g, corresponding to 92.8% of theory, is obtained (M.p. 98 to 100 ° C).

Claims (2)

Patent claims: 1. Pressureless process for the preparation of C-substituted one or two times in the 5-position Hydantoins from aldehydes or ketones and hydrocyanic acid or from the corresponding cyanohydrins by reaction with ammonia and carbon dioxide in the presence of excess amounts of ammonia and in the presence of water or organic solvents at temperatures below 60 ° C, characterized in that that in a submitted solution of 5 to 100 moles of ammonia in less than 5 moles of water, optionally as a solubilizer, in addition, methanol or ethanol may contain, at the same time each 1 mole of carbon dioxide and aldehyde or ketone cyanohydrin or instead of the cyanohydrin, slowly add 1 mol of hydrogen cyanide and aldehyde or ketone each enters. 2. The method according to claim 1, characterized in that the submitted ammonia solution is saturated. Considered publications:
German Patent No. 566 094;
U.S. Patent No. 2,603,651. 1 sheet of drawings 409 540/540 3.64 © Bundesdruckerei Berlin