DE1020341B - Process for the preparation of imidazolidone derivatives - Google Patents

Description

GERMAN

The present invention relates to a process for the preparation of imidazolidone derivatives of the general formula

R ₉ - CH - C = O

NR _-1

R ₂ -CH-CO-OR ₁

R ₃

Method of manufacture
of imidazolidone derivatives

NH

wherein R _{2 is} a hydrogen atom, an alkyl, aralkyl or aryl radical, R _{3 is} an alkyl, aralkyl or aryl radical and R _{4 is} a hydrogen atom, an alkyl, aralkyl, aryl radical or a radical - (CH ₂ ) _m —Y , with η = an integer, preferably 2 to 10, and Y = the above formula without R ₄ . One of the most important representatives of this class of substances, in which R ₂ and R _{4 are} hydrogen atoms and R _{3 is} a methyl group in the above formula, is the natural substance creatinine.

Technically, creatinine is usually obtained from creatine, which can be obtained from natural animal substances, but is also more easily accessible by synthetic means than creatinine. It is also known to be creatinine can be prepared by reacting ethyl sarcosinate with cyanamide at room temperature. According to another known method, creatinine and its homologues or derivatives can by Implementation of monosubstituted sodium cyanamides and ct-haloacetamide are produced. These two However, the latter processes have the disadvantage that the starting materials are not easily accessible.

It has now surprisingly been found that compounds of the general formula I arise can be synthesized in a particularly simple manner if one uses N-substituted α-cyanoamino fatty acid esters of the formula Applicant:

Lentia society
with limited liability,

Buying and selling,
Munich 15, Mittererstr. 3

Claimed priority:
Austria from October 30, 1956

Dr. Walter Stockmair, Linz,

and Dr. Otto Schmid, Leonding near Linz (Austria), have been named as inventors

Creatinine in the simplest way by converting cyan sarcosinic acid esters of the formula

CH ₂ -CO-OR ₁

in which R _{1 is} an alkyl, aralkyl or aryl radical and R ₂ and R _{3 have} the meaning given above, with ammonia or primary amines of the formula R ₅ -NH ₂ , where R _{5 is} an alkyl, aralkyl or aryl radical or represents the radical - (CHa) _n -NH ₂ , where η has the meaning given above.

According to the process according to the invention, CH ₃ -N

N = C

in which R _{1 has} the meaning given above, can be prepared with ammonia in good yield and high purity. By correspondingly varying the substituents R ₂ , R ₃ or R ₄ or R ₅ , however, many derivatives of creatinine, some of which were previously unknown, have become easily accessible. For example, the inventive reaction of N-substituted α-cyanoamino fatty acid esters with diamines of the general formula R ₆ NH ₂ , in which R ₅ denotes the radical - (CH ₂ ) - NH ₂ , both amino groups of the diamine having the a -Cyanamino fatty acid esters react to form previously unknown creatinine derivatives with the following formula with two creatinine residues in the molecule.

R ₂ -CH-C = OO = C CH-R ₂

R ₃ _ N N- (CHJ _n -N NR ₃

R ₃ and

NH NH

have the meaning given above).

709 808/261

Claims (3)

The inventive reaction of N-substituted example 5 Cyanamino fatty acid esters with primary amines occurs Surprisingly, by simply mixing the 16.0 parts of N-cyan sarcosine ethyl ester and 3.0 parts of ethyl Reactants at room temperature or under gelenediamine are dissolved in 40 parts of methanol and slight cooling, optionally in the presence of a 5 to 6 weeks at room temperature. Anpolar Solvent. Closing as polar solvent, 40 parts are added to the reaction mixture water can be used, acetone is particularly advantageous and left for a further 3 days at room temperature but showed the use of organic polar stand. The solid reaction product is used for work-up Solvents, especially methanol. When sucked off, washed with acetone and dried. Man Using the last-mentioned solvent the io is obtained 11.7 parts of crude 1,2-bis- [1'-methyl ^ '- imino-imide reaction product preserved especially pure. azolidon- (4 ') - yl- (3')] - ethane; this corresponds to a yield The parts given in the examples are by weight of 82.4% of theory. The raw product can through share. Recrystallize from a mixture of 35 parts of water Example 1 ^un ^ ^ parts of methanol are purified, and is obtained 15 with 9.9 parts of pure dihydrate of this compound 46.5 parts of N-cyan sarcosine ethyl ester are added to a micro-melting point (Kofler apparatus) of about stirring in 115 parts of a 320 ° cooled ^{to -1 to -5: with decomposition,}
aqueous ammonia solution with a content of. 28 parts of NH ₃ entered and then 48 hours example ό held at this temperature. For work-up, 15.6 parts of N-cyan sarcosine ethyl ester and 5.8 parts of hexadie are used precipitated crystals are suctioned off, methylenediamine is dissolved in 40 parts of methanol with alcohol, washed and dried. This gives 30.6 parts. The reaction mixture is left with room creatinine for 6 weeks; this corresponds to a yield of 82.7% of the temperature, then mixed with 40 parts of acetone Theory. and left to stand for a further 2 days at room temperature. That The preparation of the N-cyan sarcosine ethyl ester can crystalline precipitated reaction product is by Abauf the usual way isolated by reaction of / J-dimethyl suction, washed with acetone and dried, aminoacetic acid ethyl ester with BrCN or ClCN, with 11.0 parts of crude l, 6-bis- [l'-methyl-2'-imino, for example in inert solvents such as benzene, imidazolidon- (4 ') - yl- (3')] - n-hexane; that corresponds to a take place. The substance can be purified by distillation. Yield of 71.4% of theory. This crude product and transitions at 11 mm Hg at 128 °. 30 can by dissolving in 20 parts of hot methanol and This solution is mixed with 80 parts of acetone Example 2, and 8.7 parts of the pure compound result with a melting point of 190.5 to 192.5 °. 240 parts of methanol are cooled with never-. water saturated with ammonia, then 35 Example / 122 parts of N-cyan sarcosine ethyl ester, 31.2 parts of N-cyan sarcosine ethyl ester and 17.2 parts are added with stirring added dropwise and the reaction mixture via decamethylenediamine in 80 parts of methanol Left to stand overnight at room temperature. After resolved. The reaction mixture is then at 8 weeks At the end of the reaction, the crystalline precipitate is left to stand at room temperature, then with 160 suctioned off, washed with methanol and dried. 40 parts of acetone are diluted and a further 2 to 3 days receives 89 parts of creatinine; this corresponds to a yield left at room temperature. For work-up of 91.6% of theory. The reaction product which has precipitated in crystalline form according to this example is suctioned off, obtained reaction product is characterized by special washed with acetone and dried. You get Purity. 23.6 parts rawl, 10-bis- [l'-methyl ^ '- imino-imidazolidon- 45 (4 ') - yl- (3')] - n-decane; that's 64.8% of theory. the Example 3 Purification of the crude product can be achieved by dissolving in 40 parts of hot methanol and adding this solution 9.3 parts of N-cyan sarcosine ethyl ester are added at -10 ° with 120 parts of acetone. 19.9 parts are obtained dropwise in 40 parts of ethanol, 6.7 parts of pure ammonia product. The substance forms a monohydrate with dissolved contained, registered and 15 hours at this 5o a melting point of 122 to 127 °.
Temperature left to stand. The failed creatinine
is suctioned off, washed with alcohol and then dried. 6.5 parts of creatinine are obtained; this corresponds to patent claims a yield of 87.8% of theory. 1. Process for the production of imidazolidone 55 derivatives of the general formula Example ^ R ₂ -CH-C = O 14.2 parts of N-cyan sarcosine ethyl ester and 11.2 parts ^! I. Benzylamine are dissolved in 32 parts of methanol and the R ₃ - NN - R ₄ Reaction mixture stand for 4 weeks at room temperature - 60 / calmly. 80 parts of methylethyl-C are then added ketone added and left for a further 4 days at room temperature
stand. The crystalline precipitated reaction product is
isolated by suction, washed with acetone and
dried. 14.8 parts of crude 3-benzyl- 65 are obtained in which R _{2 is} a hydrogen atom, an alkyl or aralkyl creatinine; this corresponds to a yield of 72.9% of the or aryl radical, R ₃ an alkyl, aralkyl or aryl radical Theory. The crude product can be recrystallized and R _{4 is} a hydrogen atom, an alkyl, aralkyl, be purified from 150 parts of water, and one obtains aryl radical or a radical - (CH ₂ ) "- Y, with η = one in this way 12 parts of pure product with a melting integer, preferably 2 to 10, and Y = die point from 209 to 212.5 °. 70 above formula without R ₄ means thereby characterized in that one N-substituted α-cyanoamino fatty acid ester the formula R ₂ -CH
R ₈ -N CO-OR ₁ 10 in which R _{1 is} an alkyl, aralkyl or aryl radical and R ₂ and R _{3 have} the meaning given above, with ammonia or primary amines of the formula R ₅ ■ NH ₂ , in which R _{5 is} an alkyl, aralkyl or aryl radical or
implements. represents the radical - (CH ₂ ) _m - NH ₂ , 2. The method according to claim 1, characterized in that one for the production of creatinine Cyan sarcosine ester of the formula CH ₂ -CO-OR ₁
CH, - N N = C in which R _{1 has} the meaning given above, reacts with ammonia. 3. The method according to claims 1 and 2, characterized in that the reaction in polar organic solvents, preferably in methanol. © 709 808/261 11:57