DE1173102B - Process for the preparation of hydantoin derivatives of cyclic ketones with twelve ring members - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Boarding school KL: C07d

Number:
File number:
Registration date:
Display day:

German class: 12p -9

C 27668 IVd / 12 ρ
August 9, 1962
July 2, 1964

As is known, hydantoins can be converted into ketones, including cycloaliphatic ones Prepare ketones with potassium cyanide and ammonium carbonate in an aqueous alcoholic solution. It it is also known that the cyclic ketones of medium ring size differ in their behavior in the Reaction with potassium cyanide and ammonium carbonate of the ketones of smaller and larger ring sizes differ considerably. The yield in the conversion of cyclohexanone is 55% and of cycloheptanone 66%, but only 7% when converting cyclooctanone (see M. Tiffeneau, B. Tchoubar, Saias-Lambert and Le Tellier-Dupre, Bulletin de la Societe Chimique de la France [5], vol. 14 [1947], pp. 445 to 450).

British Patent 807,679, relating to processes for the preparation of 5,5-cycloheptamethylene hydantoin by reacting cyclooctanone with sodium cyanide and ammonium carbonate or by treating cyclooctanone aminonitrile related to carbon dioxide, there are no yield data for the process products obtained.

It has now surprisingly been found that hydantoin derivatives of cyclic ketones can be used with twelve ring members is obtained in high yields if either a) ketones of the formula

(CH ₂ ) Ii C = O

in which the 12-membered carbon ring can also contain double bonds, with alkali cyanide and Ammonium carbonate in an aqueous alcoholic solution or b) in a non-alkaline, aqueous alcoholic solution obtained by adding 1 mol of hydrogen cyanide to 1 mol of ketone is, quickly introduces 1 mol of ammonia gas and the aminonitrile obtained at elevated pressures and Temperatures treated with carbon dioxide or c) aminonitriles with alkali metal cyanates in the presence of hydrochloric acid under heating. The compounds obtained have the following general formula

NH-CO

CO -NH

in which the 12-membered carbon ring can also contain double bonds.

Process for the production of
Hydantoin derivatives of cyclic ketones with
twelve ring links

Applicant:

Chemical works Hüls Aktiengesellschaft,

Marl (district of Recklinghausen)

Named as inventor:
Dr. Walter Stumpf,
Dr. Konrad Rombusch,
Marl (district of Recklinghausen)

Suitable starting materials are ketones, for. B. the cyclododecanone, which is produced by the hydrogenation of Cyclododecadienones can be obtained, which in turn from the cyclododecatriene 1,5,9) by Epoxidizing and isomerizing can be obtained.

The isomer mixture of the cyclododecadienones suitable as starting material can be used in a known manner Way obtained from the cyclododecatriene (1,5,9) by epoxidation and subsequent isomerization will. This creates an isomer mixture from the cis, trans, trans-cyclododecatriene- (1,5,9) cis, trans-Cyclododecadien- (1,5) -one- (9), trans, trans-CycIododecadien- (1,5) -one- (9) and trans, trans -cyclododecadiene- (1,5) -one- (10). Analog arises from the cis, trans-cyclododecadiene- (l, 5) a mixture of the isomers cis-cyclododecenone- (5) and - (6) and trans-cyclododecenone- (5) and - (6), which are not yet described in the literature, by adding the cyclododecadiene- (l, 5) epoxidized to the also previously unknown 5,6-oxydocyclododecene and this to Cyclododecenone isomerized.

The epoxidation of cyclododecadiene (1,5) and cyclododecatriene ^ S ^), which may optionally be dissolved in solvents such as ethyl acetate and acetone, is carried out with a solution of peracids, such as performic acid, peracetic acid or perbenzoic acid, or of hydrogen peroxide and organic acids or buffer solutions in a single or multi-phase system. The reaction is generally carried out at room temperature, but it is also possible to work at lower and higher temperatures, for example at 0 and 50 ^° C., respectively.

409 628/314

Practically only the monoepoxide and only very small amounts of diepoxide are obtained. For isomerization the epoxides are then heated to 115 to 125 ° C. with stirring and then put into Amounts from 0.1 to 10 percent by weight, based on the epoxy used, one of the usual isomerization catalysts, z. B. halides, preferably magnesium iodide, too. There is a strong kick exothermic reaction. The processes described above for the preparation of the as Starting material used ketones are not the subject of the invention.

As ketones of the general formula

(CH ₂ ) I ₁ C = O

15th

For example, the following can also be used individually or in a mixture: cis-Cydododecen-one- (2), cis-cyclododecen-one- {3), cis-cyclododecen-one- (7), trans-cyclododecen-one- (2), trans-cyclododecen-one- {3), trans -cyclododecen-one- (7).

The reaction is expediently carried out in the presence of such solvents or solvent mixtures through, which dissolve the organic and inorganic reactants or at least with be able to solve progressive implementation. For example, lower alcohols such as Methyl, ethyl, propyl alcohol, also ethylene glycol, glycerine, alkyl polyglycols, mixed with Water used.

The reaction components are reacted with heating, at least a temperature of 40 ^° C. being chosen. After the above temperature is limited by incipient decomposition of the Ammoncarbonats when operating system is not pressurized, so that it should not exceed 75 ⁰ C. When working at overpressure, a temperature of about 150 ^° C. is expediently exceeded in order to avoid ring rupture.

The ketones that have been purified by distillation are, for example, each with 1 to 1.5, preferably 1.1 mol of potassium cyanide and 3 to 4, preferably 3.5 mol of ammonium carbonate, based on 1 mol of ketone, in aqueous, preferably 55% igem ethanol at 50 to 70 ⁰ C, preferably 60 to 65 ° C, implemented. The reaction time is 1 to 8 hours. The work-up can be carried out in such a way that the excess ammonium carbonate is _{decomposed at 80 to 90 ° C. to form NH 3} and CO ₂ , the majority of the ethanol also distilling off. Then it is neutralized with dilute hydrochloric acid, the crystals are filtered off and washed with water.

According to another embodiment of the claimed process, 1 mole of hydrogen cyanide is added to 1 mole of cyclododecadien- (1,5) -one in aqueous alcoholic solution. 1 mol of gaseous ammonia is quickly introduced into this approach. Are pressed to the reaction mixture containing the first resulting 1-amino-l-cyanocyclododecadien, carbon dioxide of 5 atm and heated for 2 hours at 120 ⁰ C. It is added to 1 mole of CO _2. After workup melting point is obtained in almost quantitative yield 1,3-diaza-spiro [4.1 l] -hexadecadien-dione (2,4), 237-238 ⁰ C (from ethanol). In the same way, in the analog implementation of cyclododecenone 1,3-diazaspiro [4.11 J-hexadecene-dione (2,4), C ^{o Schmelzpunkt282 from methanol) is obtained. Is used as the starting ketone cyclododecanone is obtained 1,3-diazaspiro [4, ll] -hexadecane-dione (2.4), mp 276-278 ⁰ C (from methanol). If, in the above reactions, the intermediate compound, which is present as aminonitrile, is treated not with CO 2 but with 1 mol of alkali metal cyanate, the hydantoins already mentioned are likewise obtained in 50 to 60% yield. The hydantoins obtained are colorless, high-melting compounds which, due to their anticonvulsive, sedative and hypnotic effectiveness, can be used as therapeutic agents.

example 1

A solution of 123 g of cyclododecadien- (l, 5) -one, 50 g of potassium cyanide (or 93 g of sodium cyanide) and 280 g of ammonium carbonate in 1.4155% ethanol is heated to 60 ° C. for 6 hours, then to 90 ^{° C. for 1 and} _{2 hours} ⁰ C heated under reflux. After neutralization with dilute hydrochloric acid, it is filtered off and washed several times with water. Yield 180 g (94% of theory) of l, 3-diaza-spiro-j4, ll] -hexadecadien-dione (2.4), mp 237-238 ⁰ C (from ethanol).

Example 2

A solution of 107 g cyclododecenone, 43 g of potassium cyanide and 220 g ammonium carbonate in 1.21 55 ° / pc alcohol ethanol is heated for 6 hours at 6O ⁰ C, then ¹ J ₂ hours at 90 ⁰ C under reflux. After neutralization with dilute hydrochloric acid, it is filtered off and washed several times with water. Yield 124 g (85% of theory) 1,3-diazo-spiro- [4,1J-hexadecen-dione- (2,4), melting point 282 ° C. (from methanol).

Example 3

A solution of 182 g cyclododecanone, 72 g of potassium cyanide and 400 g ammonium carbonate in 21 55% ethanol is heated for 6 hours at 6O ⁰ C to reflux. Ammonia develops vigorously under foaming. After a while, crystals will fall out. To decompose the excess ammonium carbonate, the mixture is then ^{heated to 90 °} C. for about ½ hour, the ethanol being distilled off. It is then neutralized with dilute hydrochloric acid, the crystals are filtered off and washed several times with water. Yield 22Og (87% of theory) of 1,3-diaza-spiro [4.11] -hexadecane-dione (2.4), mp 276-278 ⁰ C (from methanol).

Claims (1)

Claim: Process for the preparation of hydantoin derivatives of cyclic ketones with twelve Ring members, characterized in that either a) ketones of the formula (CHa) ₁₁ C = in which the 12-membered carbon ring can also contain double bonds, with alkali metal cyanide and ammonium carbonate in aqueous alcoholic solution at temperatures from 40 to 5 6 about 150 ° C or b) in a non-alkaline, with alkali metal cyanates in the presence of aqueous chlorine alcoholic solution, which reacts by the hydrochloric acid with heating. Add 1 mole of hydrogen cyanide to 1 mole Ketone has been obtained, rapidly 1 mole of Am- References considered: moniakgas is introduced and the amino 5 British Patent No. 807,679; nitrile at elevated pressures and temperatures Angewandte Chemie, Vol. 69 (1957), pp. 341 to 359, treated with carbon dioxide or c) aminonitriles, in particular p. 342. 409 628/314 6.64 © Bundesdruckerei Berlin