DE1212521B - Process for the preparation of symmetrical iminocarbonic acid ester derivatives - Google Patents

Description

Process for the preparation of symmetrical iminocarbonic acid ester derivatives It was. found that iminocarbonic acid ester derivatives are obtained if 2 moles of a cyanic acid ester of the general formula R-OCN in which R is a haloalkyl radical or an optionally substituted aromatic or heterocyclic radical means with 1 mole of ammonia or 1 mole of a primary aliphatic, aromatic or heterocyclic amine at temperatures from -50 to + 1500C.

The reaction is expediently carried out in a liquid medium.

The novel iminocarbonic acid ester derivatives which can be prepared according to the invention have the general formula in which R has the meaning given above and R 'stands for hydrogen, an optionally substituted aliphatic, cycloaliphatic, aromatic or heterocyclic radical.

Halogenated alkyl, alkenyl, Cycloalkyl and cycloalkenyl radicals called.

Aromatic hydrocarbon radicals are included as aromatic radicals up to 20 carbon atoms in question. Heterocyclic radicals are for example 5- and 6-membered ring systems containing one or more nitrogen, oxygen or Contain sulfur atoms and are linked to an aromatic ring system.

Substituents of the aromatic or heterocyclic radicals are, for example: Alkyl, aryl-alkylamino, acylamino, nitro, halogen, alkoxy, aroxy, acyloxy, Carbonyl, carboxyl, ester, amide, sulfonyl, ester, amide, acyl, cyano rhodanide, Alkyl mercapto, acyl mercapto.

The cyanic acid esters used can according to older proposals of the Inventor by reacting compounds containing hydroxyl groups with halogen cyanides at temperatures preferably below 65 ° C, optionally in a solvent, be prepared in the presence of a base (Chemischeberichte, 97 [1964], p. 3012).

It can be used for the inventive method, for. B. the following cyanic acid esters are used: phenyl cyanate, mono- and polyalkylphenyl cyanates such as 3 - methyl, 4- isododecyl-, 4- cyclohexyl-, 2 -tert. -Butyl-, 3-trifluoromethyl-, 2,4-dimethyl-, 3,5-dimethyl-, 2,6-diethyl-, 4-allyl-2-methoxy- phenyl cyanate; Aryl phenyl cyanates such as 4-cyanatodiphenyl; Dialkylaminophenyl cyanates such as 4-dimethylamino, 4-dimethylamino - 3 - methylphenyl cyanate; Acylaminophenyl cyanates such as acetylaminophenyl cyanate; Nitrophenyl cyanates such as 4-nitro-, 3-nitro-, 4-nitro-3-methyl-, 3-nitro-6-methylphenyl cyanate; Halophenyl cyanates such as 2 - chlorine, 3 - chlorine, 4-chlorine, 2,4-dichloro, 2,6-dichloro, 3-bromo-, 2-chloro-6-methylphenyl cyanate; Cyanatophenyl carboxylic acids, esters, amides such as 4-cyanatobenzoic acid, 2-cyanatobenzoic acid ethyl ester, 2-cyanatobenzoic acid morpholide and diethylamide; Cyanatophenylsulfonic acid, esters, amides such as 4-cyanatobenzenesulfonic acid; Alkoxyphenyl cyanates such as 2-methoxy, 3-methoxy, 4-isopropoxyphenyl cyanate; Phenoxyphenyl cyanate such as 4 - cyanatodiphenyl ether; Acyloxyphenyl cyanates such as 3-acetoxyphenyl cyanate; Acyl phenyl cyanates such as 4-acetylphenyl cyanate; Cyanophenyl cyanates such as 4-cyanophenyl cyanate; and fl-naphthyl cyanate, Anthrachinyl cyanates such as 4-cyanatoanthraquinone; Quinoline cyanates such as 5-cyanatoquinoline; Cyanatopyrazoles such as 5-cyanato-1 - phenyl - 3 - methylpyrazole, 4 - methyl mercaptophenyl cyanate, 3 - N, N - dimethylcarbamylphenyl cyanide, and the cyanic acid esters of the following alcohols: ß, ß, ß-trichloroethanol, ß, ß, ß-trifluoroethanol, ß, ß, ß-tribromoethanol, ß, ß-dichloroethanol.

The following amines can be used, for example: Primary aliphatic Amines such as methyl, i-propyl, dodecyl and i-butylamine, tert-butylamine, cyclohexylamine; primary aromatic amines such as aniline, substituted anilines, e.g. B. by chlorine, Alkyl, alkoxy groups, naphthylamine; primary heterocyclic amines such as 3-aminopyridine, 5-aminoquinoline, aminocarbazole, aminopyrazole, or substituted aminopyrazoles e.g. B. 1-Phenyl-3-methyl-5-aminopyrazole.

The reaction according to the invention can be carried out at temperatures between -50 and +150 "C, preferably -10 to +100" C.

To carry out the reaction you can, for. B. the amine or the NH8 in liquid, gaseous or dissolved form, optionally initially presented in a solvent Add cyanate, but amine or NH3, optionally dissolved, can also be initially charged and cyanate, optionally dissolved, add.

When working in the solvent, the bis-iminocarbonic acid esterimide formed falls in some cases by itself, in other cases it can be by concentration of the solvent be won.

The bis-iminokohlensäureesterimide according to the invention are new and can be used as intermediates z. B. used for the production of pharmaceuticals ver will.

Example 1 23.8 g of phenyl cyanate are presented with ether and 7.5 g of tert-butylamine in ether were added dropwise between 0 and 5 "C. After the reaction had ended is suctioned off from the precipitated product (17 g) and concentrated by concentrating the filtrate another product (8 g) obtained.

Yield to so 25 g (= 800/0 of theory). F. 102 "C.

Analysis: Calculated: C 69.5, H 6.75, N 13.5, O 10.30 / 0, molecular weight 311; Found: C 69.66, H 7.02, N 13.38, O 10.850 / 0, molecular weight 306.

Example 2 Analogously to Example 1, but in acetone as the solvent, 4-methylphenyl cyanate and aniline give the from F. 121 "C.

Analysis: Calculated. . C 73.5, H 5.85, N 11.7, O 8.90 / o; found ... C 73.75, H 5.85, N 11.95, O 9.020 / 0 Example 3 24.6 g of p-nitrophenyl cyanate are dissolved in 60 ml of dimethylformamide. A solution of 13.45 g of 1-phenyl-3-methyl-5-aminopyrazole in dimethylformamide is added at between -5 and 0.degree. After 3 hours: heating to 40 "C, dimethylformamide is distilled off to 40" C at 0.1 Torr. There remain 65 g of dimethylformamide-containing brown oil, which is stirred twice with water, then mixed with a little water and as much acetone as a flaky mass forms. Remains after suctioning off and washing with alcohol in the form of lemon-yellow crystals with a melting point of 185 "C. (from alcohol). Yield: 19.5 g (= 52% of theory) of recrystallized product.

Analysis: Calculated: C 57.5, H 3.8, N 19.6, O 19.20 / o; found: C. 57.36, H 4.02, N 19.42, O 19.520in.

Example 4 29.4 g of 2,4-dimethylphenyl cyanate are dissolved in 100 ml of ether. A slow stream of NH3 gas is passed through at the reflux temperature. White crystals separate out. After cooling, the ether is drawn off and the residue is freed from insolubles (about 2g) by being taken up again in the ether. After evaporation of the ether extract, 27 g (-82.50 / o of theory) of des from F. 108 "C back.

Analysis: Calculated: C 69.4, H 6.75, N 13.5, O 10.30 / o; found: C. 69.35, H 6.94, N 13.45, O 10.56 ° / o.

Example 5 Is 2,4-dimethylphenyl cyanate in an excess of aqueous NH3 and ensures thorough mixing by stirring well, the solidifies water-insoluble phase to crystals after some time.

After suctioning off, washing with water and drying it is as in the example 4 separated from little insolubles by taking up in ether and the product through Evaporation of the ether extract won.

The same product is obtained as in Example 4 (F. 107 "C, identical IR spectrum).

Example 6 23.8 g of phenyl cyanate are placed in 50 ml of benzene, and NH3 is passed over at room temperature for 2 hours. The temperature rises and is kept at about 40 ° C. After concentration of the solvent and recrystallization from benzene-ligroin, 25 g (= 910/0 of theory) of des from F. 81 "C.

Example 7 14.9 g of 2-methoxyphenyl cyanate are placed in 50 ml of ligroin, and a dry stream of NH3 is passed over it with vigorous stirring. A white crystal pulp is formed which is recrystallized from benzene after evaporation of the solvent. This gives 15 g (= 19% of theory) of the from F. 98 "C.

Analysis: Calculated: C60.9, H5.4, N13.3, O20.30 / o; found: C 60.44, H 5.55, N 13.58, O 20.330 / 0.

Example 8 Analogously to Example 4, ethyl cyanate and NH 3 are obtained from B, B, ß-trichloro from F. 61 to 62 "C.

Analysis: Calculated: C 19.4, H 1.88, N 11.3, O 8.62, Cl 58.80 / o; found: C 19.9, H 2.12, N 11.46, O 8.56, Cl 58.00 / 0.

Example 9 3.1 g of gaseous methylamine are dissolved in 15 g of absolute methanol blown in and released.

23.8 g of phenyl cyanate, diluted with 30 ml of ether, are added dropwise at 0 ° C. 17 g des precipitate as crystal pulp and are obtained by suction.

F. 119 to 1200C (from benzene-ligroin). By working up the filtrate you can increase the yield.

Analysis: Calculated: C 66.95, H 5.58, N 15.6, O 11.90 / o; found: C 67.01, H 5.59, N 15.49, O 12.190 / 0.

Claims (2)

Claims: 1. Process for the preparation of symmetrical iminocarbonic acid ester derivatives, characterized in that 2 moles of a cyanic acid ester of the general formula R-OCN in which R is a haloalkyl radical or an optionally substituted aromatic or heterocyclic radical, with 1 mol of ammonia or 1 mol of a primary aliphatic, aromatic or heterocyclic amine at temperatures from -50 to +150 "C to form compounds of the general formula reacted, in which R has the meaning given above and R 'stands for hydrogen, an optionally substituted aliphatic, cycloaliphatic, aromatic or heterocyclic radical. 2. The method according to claim 1, characterized in that the Implementation in a liquid medium.