IE52262B1 - Preparation of oxazolidine-2,4-diones - Google Patents

Abstract

1. A process for the preparation of oxazolidine-2,4-diones or the formula see diagramm : EP0056966,P6,F4 where R**1 is naphthyl, or phenyl which is unsubstituted or substituted by one or more halogen atoms, methyl or methoxy, R**2 is hydrogen, alkyl of 1 to 4 carbon atoms, halogen, vinyl, methoxymethyl or carboethoxy, and R**3 has the same meanings as R**2, R**2 and R**3 being identical or different, or R**2 and R**3 are bonded to one another and each is methylene, by reacting a hydroxycarboxylic acid amide with a diorganyl carbonate, wherein an amide of the formula see diagramm : EP0056966,P7,F1 where R**1, R**2 and R**3 have the above meanings, is reacted with a carbonic acid ester of the formula see diagramm : EP0056966,P7,F2 where R**4 is phenyl which is unsubstituted or substituted by methyl or halogen and R**5 has the same meaning as R**4, or R**4 and R**5 together are 1,2-phenylene, at from 50 to 250 degrees C, and the phenols R**4 OH and R**5 OH formed during the reaction are isolated, preferably by distillation.

Description

The present invention relates to a novel process for the preparation of oxazolidine-2,4-diones by reacting a substituted amide with an aromatic carbonic acid ester.

The preparation of oxazolidine-2,4-diones by reacting 5 an isocyanate with a 2-hydroxycarboxylate has been disclosed in German Published Application DAS 1,811,843 and German Laid-Open Applications DOS 2,022,494 and DOS 2,207,576.

The conversion of a substituted urea derivative by means of diphenyl carbonate to form a compound with a 6-membered ring including 3 nitrogen atoms has been disclosed in French Patent Application 2,316,239, and the conversion of a primary hydroxycarboxamide by means of a dialkyl carbonate and a stoichiometric amount of a metal alcoholate in two stages to form an oxazolidine dione has been disclosed in US Patents 2,338,220 and 2,909,467. The process of the present invention is not closely related to those known processes because in the latter either completely different starting materials and products are involved or the process is carried out in a fundamentally different way.

We have found that an oxazolidine-2,4-dione of the formula O, R -N R' ,2 R' ,3 226 2 - 3 1 where R is naphthyl or is phenyl which xs unsubstxtuted or substituted by one or more halogen atoms, methyl or 2 methoxy, R. is hydrogen, alkyl of 1 to 4 carbon atoms, halogen, vinyl, methoxymethyl or carboethoxy, and 2 ? 3 R is selected from the same meanings as R , Ir and R 2 being identical or different, or R and R are bonded to one another and each is methylene,' is obtained in very good yield when an amide of the formula / -NH-CO-C 1 \ 3 OH IT where R^, R^ and R3 have the above meanings, is reacted with an aromatic carbonic acid ester of the formula R -0-C-O-R II where R is phenyl which is unsubstituted or substitued by methyl or halogen and R^ is selected from the same mean15 ings as R4, or R^ and R^ together are 1,2-phenylene, at from 50 to 250°C, and the phenols R^OH and R^OH formed during the reaction are isolated. - 4 Examples of R1 are phenyl, naphthyl, 2-, 3- and 4-fluorophenyl, 2-, 3- and 4-chlorophenyl, 2-, 3- and 4bromophenyl, 2,3-dichloropheriyl,--2,3,6-triehlorophenyl, 2-, 3- and 4-methoxyphenyl, 2-, 3- and 4-methylphenyl, 3,4dichlorophenyl, 2,6-dichlorophenyl, 2,3,4-trichlorophenyl, 2,3,5-trichlorophenyl and preferably 3,5-dichlorophenyl. 3 Examples of R and R are hydrogen, vinyl, alkyl, eg. methyl or ethyl, methoxymethyl and carbethoxy.

Examples of R and R are 4-methylphenyl, 4-chlorophenyl and, preferably, phenyl; alternatively R4 and R5 together are 1,2-phenylene The reaction must be carried out at from 50 to 250°C, preferably at from 120 to 170°C.

It is important that the aromatic carbonic acid ester be substantially pure (for example, free from phenyl chloroformate and acid impurities).

The reaction can be carried out without a catalyst, but to obtain as quantitative and rapid a conversion as possible, ie. a high space/time yield, the addition of the following basic catalysts can be advantageous: alkali metal aleoholates, eg. sodium methylate or sodium ethylate, amines, eg. tertiary amines (tripropylamine or tributylamine) and alkali metal phenolates of the formula R40®Me+ - 5 where R4 has the above meaning and Me is an alkali metal (eg. sodium phenolate). For example, from 0.01 to 0.1 mole per cent of the catalyst is added, based on the amide.

The reaction is advantageously carried out without a solvent.

If a solvent is used, its boiling point should be • 4 5 above those of the phenols R OH and R OH.

It is surprising that the reaction with the diaryl carbonate can be carried out very rapidly and without a catalyst.

If a good yield Is to be obtained in the reaction, it is important that the resulting phenols R OH and R OH are isolated substantially quantitatively, preferably by distillation, and that care is taken to ensure that the diaryl carbonate used as the starting material does not distill with the phenols. For this purpose, it is particularly advantageous to use a packed distillation column.

The phenols R OH and R OH which have been distilled off are obtained sufficiently pure to be recycled directly to the preparation ofR^-O-C-O-R^. tl The reaction can be carried out under atmospheric pressure, but reduced pressure of about 1 mbar to 950 mbar can be advantageous for reducing the distillation temperature .

The amides used as starting materials are formed, for example, as by-products in the conventional preparation of the corresponding oxazolidine-2,4-diones. - 6 The amides are also formed in the alcoholysis of the corresponding oxazolidine-2,4-diones with ethylene glycol or glycerol.

The process can be generally represented as follows: R -NH-CO-C x OH „1 H 2 R-\XR + R**-O-C-O-R5 n 0 + R^OH + R5OH H c The cheaper reactant, for example R -O-C-O-R , can be employed in excess (eg. 1.1 mole of ester per mole of amide).

The novel process is conveniently carried out as described 10 in the Examples below: EXAMPLE 1 52263 - 7 26 g (0.1 mole) of N-(3,5-dichlorophenyl)-2hydroxy-2-methylbut-3-enoylamide and 21.4 g (0.1 mole) of diphenyl carbonate are heated at 160-165°C. About 18.4 g of phenol pass over at 88-95°C undey a pressure of about 30 mbar. The residual melt is cooled to about 80"C and 25 ml of methanol are added. The mixture is stirred for 2 hours and cooled to 5°C. The product is filtered off under suction and then washed with twice 10 ml of methanol and subsequently with 50 ml of water.

Yield: 26.7 g of 99% strength 3-(3,5-dichlorophenyl)-5-methyl-5-vinyl-l,3-oxazolidine-2,4-dione (= 92.4% yield calculated for a 100% strength product). M.p.: lll’C; the product is pure according to thin layer chromatography.

EXAMPLE 2 N-(3,5-Diehlorophenyl)-5-methyl-5-methoxymethyl-oxazolidine-2,4-dione 27.8 g (0.1 mole) of N-(3,5-dichlorophenyl)-2hydroxy-2-methoxymethylpropionamide, 21.4 g (0.1 mole) of diphenyl carbonate and 0.7 g (0.01 mole) of sodium ethylate - 8 are heated at 140-145°C. The resulting phenol is distilled off in the course of 1 hour at 88-102°C/22 mbar.

The residue is cooled to 70°C, 75 ml of methanol are added and the mixture is stirred at 15°C for 2 hours. The product is filtered off under suction, and washed with twice 10 ml of water and dried.

Yield: 13 g of N-(3,5-dichlorophenyl)-5-methyl5-methoxymethyl-oxazolidine-2,4-dione, corresponding to 85.5%. M.p.: 112°C (the product is pure according to thin layer chro10 matography). Strength: 100% (determined by high pressure liquid chromatography).

The Instructions which follow describe the preparation of the amides by alcoholysis.

INSTRUCTION 1 N-(3,5-Dichlorophenyl)-2-hydroxy-2-methylbut-3-enoylamide 214.5 g (0.75 mole) of 3-(3,5-dichlorophenyl)-5methyl-5-vinyl-l,3-oxazolidine-2,4-dione, 750 ml (13.5 mole) of ethylene glycol and 8.25 g (0.056 mole) of tripropylamine are stirred at 150°C for 2 hours.

The residual ethylene glycol is then distilled off at about 80°C on a rotary evaporator, under reduced pressure - 9 from a pump (about 0.2 mbar). The residue»which crystallizes on standing overnight, weighs 198 g and can be reciystallized from 150 ml of toluene'. 128 g of N-(3,5-dichlorophenyl)-2-hydroxy-2-methyibut-3-enoylamide of melting point 116’C are obtained. The structure is confirmed by the IR and H-NMR spectra. Analysis C H 0 N Cl found: 50.9 4.4 12.3 5.9 27.2 calculated: 50.8 '4.2 12.3 5.4 27.3 10 INSTRUCTION 2 N-(3,5-Dichlorophenyl)-2-hydroxy-2-methoxymethylpropionamide Cl 0 .4 g (0.1 mole) of N-(3,5-dichlorophenyl)-5methyl-5-methoxymethyl-oxazolidine-2,4-dione, 100 ml (1.8 mole) of ethylene glycol and 1.1 g (0.0075 mole) of tripropylamine are stirred at 150°C for 2 hours.

Working-up is carried out as described in Instruction 1, and the product is recrystallized from toluene.

Yield: 22 g (= 79.1%) of N-(3,5-dichlorophenyl)-2hydroxy-2-methoxymethylpropionamide of melting point 140°C.

Claims (8)

CLAIMS 53363

1. A process for the preparation of an oxazolidine-2,4dione of the formula where R 1 is naphthyl or is phenyl which is unsubstituted or substituted by one or more halogen atoms, methyl o or methoxy, R is hydrogen, alkyl of 1 to 4 carbon atoms, ο halogen, vinyl, methoxymethyl or carboethoxy, and R is 2 2 3 selected from the same meanings as R , R and R being 2 3 identical or different, or R and R are bonded to one another and each is methylene, wherein an amide of the formula / -NH-CO-C-R OH 12 3 where R , R and R have the above meanings, is reacted with a carbonic acid ester of the formula 4 5 R -O-C-O-R 3 II where R is phenyl which is unsubstituted or substituted 5 by methyl or halogen and R is selected from the same meanings 4 4 5 as R , or R and R together are 1,2-phenylene, at from 50 to 250°C, and the phenols R^OH and R^OH formed during the reaction are isolated.

2. A process as claimed in claim 1, wherein the phenols R 4 OH and R^OH are isolated substantially quantitatively by distillation.

3. A process as claimed in claim 1 or 2, wherein the - 11 reaction is carried out with an amide in which R 1 is 3,52 3 dichlorophenyl, R is methyl and R is vinyl.

4. A process as claimed in claim 1 or 2, wherein the reaction is carried out with an amide in which R 3 is 3,52 3 5. Dichlorophenyl, R is methyl and R is methoxymethyl.

5. A process as claimed in any of claims 1 to 4, carried out in the presence of a basic catalyst.

6. A process as claimed in claim 5, wherein the basic catalyst is an alkali metal alcoholate, an amine or an 4 Θ © 10 alkali metal phenolate of the formula R 0 Me , where R has the meaning given in claim 1 and Me denotes an alkali metal, and is used in an amount of from 0.01 to 0.1 mole per cent based on the amide.

7. A process for the preparation of an oxazolidine-2,415 dione from a corresponding amide and an aromatic carbonic acid ester carried out substantially as hereinbefore described or illustrated in either of the foregoing Examples 1 and 2.

8. An oxazolidine-2,4-dione when prepared by a process as claimed in any of claims 1 to 7.