DE1670762A1 - Process for the preparation of 2-amino-5-aryl- or alkyl-oxazolidinones- (3) - Google Patents

Description

Process for the preparation of 2-amino-5-avyl- or alkyloH Bs is known that 2-aaino-5-phenyl-oxazolidinone- (3) is obtained when mandelic acid esters are used reacted with guanidine (U. S.

Patent 2,892,753).

It has now been found that 2-amino-5-aryl or. alkyloxazolidinone- (3) is obtained in a simple manner if a) carboxylic acid ester of the general formula in which Ri denotes a lower alkyl or an aryl group, R2 denotes an alkyl or optionally substituted aryl group, with a cyanic acid ester of the general formula ROCN in which R denotes a haloalkyl or an optionally substituted aryl group which can also be linked to a heterocyclic compound , and then with at least the stoichiometrically required amount of ammonia at temperatures from about -20 to about 100 ° C., optionally in the presence of a base, or b)) carboxamides of the general formula where R2 has the abovementioned meaning with a cyanic acid ester of the general formula ROCN where R has the abovementioned meaning at temperatures from about -20.degree. C. to about 100.degree. C., optionally in the presence of a base, su don compounds of the formula where R2 has the meaning given above.

Haloalkyl radicals R are, for. B. Hydrocarbon residues with up to 12 Carbon atoms, which are preferably fluorine, bromine, chlorine or iodine atoms in the ß-position wear.

All aromatic radicals R come from aromatic hydrocarbon creations with up. to 20 carbon atoms in the ring system.

The aromatic radicals R can optionally at least one of carry the following substituents exemplified: alkyl, aryl, alkylamino, Acylamino, nitro, halogen, alkoxy, aroxy, acyloxy, carbonyl, carboxyl, carbon esters, -amid-, sulfonyl-, sulfonic acid ester, -amid-, acyl-, cyano-, rhodanide-, alkylmercapto-, Aryl mercapto or acyl mercapto groups.

Ri should preferably be a hydrocarbon radical with up to 6 carbon atoms or represent a phenyl radical ..

Alkyl radicals R2 are preferably those with up to 6 carbon atoms (also cycloalkyl), as optionally substituted aryl radicals, preferably phenyl and naphthyl, optionally at least one of the following examples carry the named substituents: alkyl (preferably up to 6 carbon atoms), Aryl (preferably phenyl), alkylamino (preferably up to 4 carbon atoms), Acylamino (preferably up to 4 carbon atoms in the carboxylic acid residue), nitro, Halogen, alkoxy (preferably up to 4 carbon atoms), aroxy (preferably Phenoxy), acyloxy (preferably up to 4 carbon atoms in the carboxylic acid residue), Carbonyl, carboxyl, carbon ester (preferably up to 6 carbon atoms in the ester group as well as phenyl ester), carbonamide, sulfonyl, sulfonic acid ester (same scope of meaning how Carboxylic acid ester), sulfonic acid amide, acyl (preferably up to 4 carbon atoms in the carboxylic acid residue and benzoyl), cyano, rhodanide, alkyl mercapto (preferably up to 4 carbon atoms), aryl mercapto (preferably phenyl mercapto) or acyl mercapto groups (Scope of meaning as with acyl).

All output connections used CyansEureeeter can according to own older proposals through implementation of compounds containing hydroxyl groups with halogen cyanides at temperatures preferably below + 65 ° C, if necessary in a solvent in the presence of a base (reports from Deutechen Chemischen Gesellschaft 97, 3012 (1964)).

For the process according to the invention, 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-methoxyphenylcyamet; Aryl phenyl cyanates such as 4-cyanatodiphenyl, 4, 4'-biscyanatodiphenyl; Dialkylaminophenylcyanate 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; Cyanatophenylcarboxylic acid, esters, amides such as 4-cyanatobenzoic acid, 2-pyanatobenzoic 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-cyanatodiphenyl ethers; Acyloxyphenyl cyanate such as 3-acetoxyphenyl cyanate; Acylphenyl cyanates such as 4-acetylphenyl cyanate; Cyanatophenyl cyanates such as 2,3-dicyano-1, 4-dicyanatobenzene; α- and ß-naphthyl cyanate, anthrachinyl cyanate such as 1,4-dicyanatoanthraquinone; Quinoline cyanates such as 5-cyanatoquinoline; 1, 4-phenylene dicyanate, 1, 5-naphthylenedicyanate, 1, 3, 5-tricyanatobenzene, 4, 4'-biscyanatodiphenyldimethylmethane, 4,4'-Biscyanatodiphenyl-Cyclohexan-1, 1 2,2'-Biscyanatodinaphtyl, 4-Methylmercaptophenylcyanat, 3-N, N-dimethylcarbamylphenyl cyanate, and the cyanate esters of the following alcohols: B, B, ß-trichloroethanol, B, ß, ß-trifluoroethanol, ß, ß, ß-tribromoethanol, ß, ß-dichloroethanol, H (CF2-CF2) 5CH2OH.

Ale carboxylic acid esters can be used, for example: Mandelic acid methyl, -äthyl-, -propyl-, -isopropyl-, -n.butyl-, -isobutyl -, - tert. butyl, hexyl, phenyl ester and the corresponding derivatives of lactic acid, o-hydroxypropionic acid and o-hydroxyeapronic acid.

Ala carboxamides can be used, for example, Msndelstureamide, lactic acid amide, o-hydroxypropionic acid or o-hydroxycaproic acid amide. The method according to the invention is illustrated by the following examples: The reaction in section a) is carried out in such a way that the carboxylic acid ester, optionally in the presence of a base, is first reacted with cyanic acid ester and then with at least the stoichiometrically required amount of ammonia (especially aqueous ammonia, but also gaseous ammonia or ammonia).

Bbsung of ammonia in an inert organic solvent) for example by pouring the intermediate compound onto aqueous ammonia. That The reaction product falls out and is filtered off with suction.

In case b) falls in the implementation of the carboxamide with cyanate, optionally in the presence of bases, the ead product is produced directly and is carried out by Suction won.

All solvents come e.g. organic solvents such as alcohols, Ketones, ethers, nitriles, buters, amides, eromatic and aliphatic, optionally nitrated or halogenated hydrocarbons or water or water. It are mentioned here, for example: methanol, Xthanol, Boston, diethyl ether, acetonitrile, Acetic acid, r dimethylformemide, benzene, petroleum ether, nitrobenzene, nitromethane, chloroform, Carbon tetrachloride, chlorobenzene.

All bases which promote the reaction can, for example, be used in catalytic agents until molar amounts are added: alkali hydroxides, carbonates, amides, hydrides, alcoholates, -metals e.g. NaOH, KOH, Na2CO3, NaNH2, NaH, NaOCH3, Na or tert. organic amines such as B. triethylamine, dimethylbenzylamine or pyridine.

The compounds accessible by the method according to the invention are valuable intermediates, for example on the manufacture of pharmaceuticals.

2-Amino-5-phenyl-oxazolidinone- (3) is known as a medicine.

(US Patent 2,892,753) Example t 200 mg of sodium metal are dissolved in 25 ml of absolute Athsnol, first 10.5 g (0.062 mol) of mandelic acid ethyl ether and then 7.44 g (0.062 mol) of phenyl cyanate are added. Temperature rise from room temperature to bi. s 55 ° C. The slightly red colored charge is after a short time serdunnt with tasser and extracted with ether. The yellow oil obtained from the ether extract (16.5 g 92% of theory) is mixed with an excess of aqueous, concentrated NH3 solution crystallizes sus. F.: 255 to 256 ° C Identification: The IR spectrum is identical to that of an authentic sample.

Example 2 For a solution of 18.0 g (0.1 mol) of mandelic acid ester 3 ml of triethylamine are added to 60 ml of acetone and then 11 (0.1 Moles) phenyl cyanate. After processing analogously to Example 1, 29.5 is obtained g (= 98% of theory) of the yellow oil, which as in Example 1 in the End product is convicted.

Example 3 Analogously to Example 2, instead of acetone, alcohol is added to 6Q ml worked. Instead of 3 ml of triethylamine, 6 drops of concentrated aqueous NaOH are added added. 29 g (97% of theory) of the yole, which is further processed as in Example 1, are obtained will.

Example 4 15.1 g (0.1 mol) of mandelic acid amide are dissolved in 50 ml of alcohol presented, 6 drops of concentrated NaOH added and 11.9 g (0.1 mol) phenyl cyanate dripped in. The exothermic half-hour reaction is intercepted by cooling at 40 ° C. After @ NachrUhren, plenty of water is added, and the product which precipitates out crystallizes. After wiping onto clay, 16.1 g (= 91.5% of theory) of the same product are obtained as in Example 1 (identical IR spectrum) from 254 to 256 ° C.

Example 5 35.4 g (0.3 mol) of ethyl lactate are dissolved in 150 ml Submitted acetone, first 1 ml of NaOH (aqueous concentrated) and then slowly 39.3 g (0.3 mol) of 4-methylphenyl cyanate were added.

Temperature rise from 20 to 48 ° C, again after the reaction has subsided 0.5 ml of concentrated NaOH added. Another rise in temperature. After 10 minutes is filtered off, rendered neutral (with HCl) and concentrated in vacuo. The remaining oil is mixed with 25 ml of ammonia and a little alcohol.

Of crystallizes out, is pressed onto clay and the alcohol / H2O is not crystallized. F. 225 to 226 ° C; Yield: 17.5 g (51% of theory) Analysis: C4H6N2O2 (molecular weight 114) cxxa calc. : 42.0% 5.26% 24.6% 28.1%: 42.48% 5.50% 24.45% 27.94%

Claims (1)

Process for the preparation of 2-aminooxazolidinones (3) substituted in the 5-position, characterized in that a) carboxylic acid esters of the general formula R2 - CH - COOR1 OH in which Ri is a lower alkyl or an aryl radical, R2 is is an alkyl or optionally substituted aryl radical, with a cyanic acid ester of the general formula ROCN in which R is a haloalkyl or an optionally substituted aryl radical, which can also be linked to a heterocycle, and then with at least the stoichiometrically required amount of ammonia at temperatures of about -20 to about 100 ° C., optionally in the presence of a base, or b) carbonegureamides of the general formula where R2 has the abovementioned meaning ng, with a cyanic acid ester of the general formula ROCN in which R has the abovementioned meaning, at temperatures from about -20 ° to about 100 ° C., optionally in the presence of a base, to give the compounds of the formula where R2 has the meaning given above.