DE3003653A1 - N-substd. oxazolidine-2,4-di:one derivs. prodn. - by one-pot reaction of alkali cyanate with organic halide and alpha-hydroxy carboxylic acid ester - Google Patents

Abstract

In a new process for the prodn. of N-substd. oxazolidine-2,4- dione derivs. (I) by reaction of isocyanates O=C=N-(CA2)n-(CO)m-R (III) with alpha-hydroxy carboxylic acid esters (IV), the isocyanate is generated from an alkali cyanate and an organic halide X-(CA2)n-(CO)m-R1 (V) in the presence of the alpha-hydroxy carboxylic acid ester HOCR2R3COOR4 (IV), the molar ratio of (V) to (IV) is 2:1 to 1:10, reaction temp. is 20-200 deg.C, and the reaction is carried out in the presence or absence of a polar aprotic solvent; (where n and m are 0 or 1; each A (same or different) is H, Me or Et; R2 and R3 are H, opt. halogenated and/or unsaturated 1-4C alkyl, or 6-10C acyl, aralkyl or cycloalkyl; R1 is a group Y or Z; Y is opt. unsaturated 1-4C alkyl or 1-4C alkoxy, opt. substd. by halogen, CN, trihalomethyl or alkoxy; Z is aryl, aryloxy, thioaryl, aralkyl, aralkoxy or cycloalkyl opt. ring-substd.by halogen, CN, NO2, trihalomethyl and/or alkoxy; and X is Cl, Br or I). Cpds. (I) in which m is 1, R1 is 1-4C alkyl or alkoxy and R2 and R3 are H, opt. unsaturated and/or halo-substd. 1-4C alkyl or 6-10C aryl, aralkyl or cycloalkyl are new and claimed. (I) are useful as pesticides and pharmaceuticals or intermediates for pesticides and pharmaceuticals, as stabilisers for plastics, and as additives for lubricants. Simple process enabling (I) to be obtained from organic halides in a single process step.

Description

Process for the preparation of B-substituted oxazolidine

diones- (2,4) It is known that oxazolidinediones of the general formula (I) in which R1 and R2 are hydrogen atoms or optionally halogenated alkyl or alkenyl radicals, or together represent the alkylene radical, by reacting 3,5-oxychlorophenyl isocyanate with an α-hydroxycarboxylic acid ester of the formula (DE-PS 1 811 843; DE-OS 1 207 576).

In this implementation, relatively large amounts of tertiary amines are used needed as catalysts. In addition, the required isocyanate must be used of highly toxic phosgene from the base aniline.

Another process for the preparation of oxazolidine (2,4) dienes, in the case of the hydroxycarboxylic acid ester, not with isocyanates but with carbamic acid esters has been implemented (0E-0S 2 813 873), does not eliminate these disadvantages in principle, since the production of the carbamic acid esters is preferably carried out by converting isocysshates takes place with low molecular weight alcohols, so that in comparison to the aforementioned Reactions even an additional reaction Level required is. Finally, DE-OS 2 827 414 describes a process in which urea which are also by-products of isocyanates, are used.

It has now been found that N-substituted oxazolidinediones (2,4) of the general formula (II) which also include the above-mentioned9 already known oxazolidinediones (2,4) of the formula (I). can be prepared in a much simpler manner in a single process step from an organohalide and an α-hydroxycarboxylic acid ester in the presence of an alkali metal cyanate.

The present invention therefore relates to a process for the preparation of N-substituted oxazilidinedione- (2,4) of the general formula (II) in which n and m have the meanings zero or 1, A is identical or different and H, CH3 or C2H5, R² and R³ represent hydrogen or a saturated or unsaturated alkyl radical with up to 4 carbon atoms, which can also be halogen-substituted or are an aryl, aralkyl or cycloalkyl radical with 6 to 10 carbon atoms, and R1 is a group Y or a group Z, where Y is a saturated or unsaturated alkyl radical with up to 4 carbon atoms or an alkoxy radical with the same number of carbon atoms , and these radicals' can be substituted by halogen, cyano, trihalomethyl or alkoxy, while Z represents an aryl, aryloxy, thioaryl, aralkyl, aralkyloxy or cycloalkyl radical, each of which is also one or more times by halogen, cyano, nitro , Trihologonmothyl or Alkoxi ring-substituted, by reacting an isocyanate of the general formula (III) O = C = N- (CA2) n- (CO) m -R¹ (III) with an α-hydroxycarboxylic acid ester of the general formula (IV ) in which R4 denotes an alkyl radical with 1 to 4 carbon atoms, which is characterized in that the isocyanate (oil) is obtained from alkali metal cyanate and an organohalide of the general formula (V) X- (CA2) n- (CO) m-R¹ (V) in which X = C17 Br or J, generated in situ in the presence of the α-hydroxycarboxylic acid ester (IV), the molar ratio of (V): (IV) being in the range from 2: 1 to 1:10 , the reaction temperature is 20 to 200 e and one works in the presence or absence of a polar, aprotic solvent.

Since it is known from the literature that containing exchangeable halogen Compounds in the reaction with alkali cyanates, skipping the monomer stage Trimerizing cyanates directly to isocyanurates was the formation of compounds of type (II) in the reaction of organohalides of type (V) with alkali metal cyanate not expected. It was to be expected that the isocyanates initially formed of the formula (III), before they react with the hydroxycarboxylic acid esters (IV), likewise pass into isocyanurates, moreover it is known that alcohols, which are the same Have OH functionality like the compounds of substance class (IV) 9 when they are produced of isocyanurates from halocarboxylic acid esters can serve as solvents n (see DE-PS 812 312). However, completely unexpectedly for the person skilled in the art, I found that the isocyanurate formation in the present system is practically completely absent, The process according to the invention is carried out in the presence or absence of an aprotic solvent carried out. When working in the absence of a solvent, preference is given to using the α-hydroxycarboxylic acid ester (IV) for the purpose of increasing the polarity of the reaction solution in excess one. This procedure is particularly advantageous because the reaction equilibrium is favorably influenced. in general, the molar ratio of (V): (VI) should be between 2: 1 and 1:10, preferably 1: 1 and 1:10. As polar, aprotic solvents are suitable e.g. 0. Dioxane, glycol dimethyl ether, diglycol dimethyl ether, tetrahydrofuran, Dimethyl sulfoxide, dimethylformamide and phosphoric acid tris-dimethylamide.

The molar ratio of alkali metal cyanate: organohalide ranges between 1: 1 and 2. 1, whereby in general a small excess of alkali metal cyanate, accordingly a molar ratio of 1.1: 1 is sufficient.

The implementation is at temperatures between 20 and 200, preferably between 50 and 150 and in particular between 50 and 100 ° C carried out and is, if not working under pressure, the lowest due to the boiling point boiling reaction component or the concomitantly used aprotic solvent means limited. Sometimes it is useful to use small amounts (0.01 to 3% by weight, based on component V), of secondary or tertiary amines as catalysts to add.

Suitable α-hydroxycarboxylic acid esters (IV) are, for. B. methyl, Ethyl, propyl, isopropyl, n-butyl and isobutyl esters of the glycol, milk and Mandulic acid, as well as derivatives of these acids. These include: α-Hydroxipropion-, α-hydroxy-n-butyric acid, α-hydroxyisobutyric acid, a-vinyl, a-1 -bromovinyl, α-propan-1-yl, α-2-bromopropen-1-yl, α-3-bromo-propen-1-yl-, α-2,2-dimethylvinyl-, α, ß, ß-trimethyl and ß, ß, ß-trimethyl lactic acid.

Among organohalides, which are characterized by the formula (V) are understood as: monohalogenation products of straight and branched chain, saturated and unsaturated alkanone or cycloalkenes, the ethyl, ethyl, propyl, Isopropyl, n-dutyl and isobutyl esters of chloramic acid and other halogen fatty acids namely chloro, bromo and iodoacetic acid, α-chloro and α-bromopropionic acid and the a-chlorine-n- hzw. α-chloro-isobutyric acid. Also mentioned are z. B. Monochloroacetonitrile, monochlorodimethyl ether, bromobenzene and iodobenzene, 2-nitro and 2,4-dinitrochlorobenzene, 2-nitro-4-trifluoromethylchlorobenzene, 4-nitro- and 5-chloro-2-nitroanisole, 2,6-dinitro-4-trifluoromethyl-chlorobenzene, 2,4-dichlorobenzyl chloride, 2,3,4,5,6-pentachlorobenzyl chloride, α-chloro- and α-bromoacetophenone.

Of the compounds obtainable by the process according to the invention of the formula (II), as already mentioned, some are known, but the following are new, in which n stands for zero or 1, in for 1 and R1 for O-alkyl or alkyl with 1 to 4 carbon atoms.

The process products are suitable for use on the pest control and the pharmaceutical sector, as stabilizers for the plastics sector and as additives to lubricants.

They can also be used as intermediates for the synthesis of other Find pesticides and pharmaceutical preparations use.

Example 1 In one with stirrer, thermometer and reflux condenser A 1 liter stirred flask provided with the outlet becomes a suspension of 71.5 g = 1.1 mol of sodium cyanate and 40090 9 presented acetonitrile. The suspension is stepped one after the other with stirring 9090 9 = 1 mole of methyl glycolate 12295 g = 1 mole of ethyl monochloroacetate and then 490 g of triethylamine (= 1% based on acetonitrile).

The suspension is stirred at 80 ° C. for 22 hours. The ion chlorine determination in the salty soil body showed a complete conversion with 5292%.

It is filtered, the salt residue on the filter is washed twice with 65 g of acetonitrile each time and the filtrate, including the washing liquids, is concentrated in a rotary evaporator. The initially pasty residue solidifies when standing. It is extracted with 50% ethanol and then a total of 114.8 g of 3-carbnthoxj.-mothyl-oxazolidin-dione - (2,4) of the formula which melts at 62 to 65 ° C. crystallize out of this % C: 44.9 (Th: 45.2); % H: 5.4 (Th: 5.4); % N: 14.8 (Th: 15.0) Example 2 The procedure was as in Example 1, except that 118.13 g = 1 mol of d, 1-lactic acid ethyl ester were used instead of the methyl glycolate.

The reaction time was 8 1/2 hours at 80 oC.

The pipe product isolated as in Example 1 is a brownish, viscous one Liquid that can be subjected to vacuum distillation at approx.

0.3 mbar is subjected. The liquid at room temperature is obtained 3-Carbethoxymethyl-5-methyl-oxazolidin-dione- (2,4) in a yield of almost 100%. Bp 0.3: about 114 ° C% C: 47.9 (Th: 47.8); % H: 5.8 (Th: 5.6); % N: N: 7.3 (Th: 6, gjr) Example 3 The procedure was as in Example 2, but instead of ethyl monochloroacetate 1 mol = 126.6 g of Bonzylchlori (d one sets.

After the work-up carried out according to Example 1, the residue remains 180.6 g of a slightly reddish color that gradually crystallizes on standing Liquid which turns out to be slightly contaminated 3-Benzyl5-methyl-oxazolidin-dione- (2,4) proved (expansion approx. 88.1%). M.p. after recrystallization from ethanol: 75 to 77 'C.

% C: 64.4 (Th: 64.3);% H: 5.4 (Th: 5.4); % N: 6.9 (Th: G, 8) Example 4 The approach of Example 1 was modified in such a way that instead of 1 mol of ethyl monochloroacetate 1 mole of p-nitrobenzyl chloride was used.

After a reaction time of eleven hours at 80 ° C., work-up was carried out as described. There remained 218.7 g of a corner-colored, partially crystalline paste, which was removed by expelling with 150 ml of a mixture of 5 parts by volume of diethyl ether and 1 uolumentsil acetonitrile disintegrated into a powder. The melting point of the same was 123 to 140 ° C. after dom drying. After recrystallization from ethanol, the 3-p-nitrobenzyl-oxazolidine-diene- (2,4) obtained in this way had mp 156-159 ° C.

% C: 50.7 (Th: 50.8); % H: 3.4 (Th: 3.4):% N: 11.9 (Th: 11.9) Example 5 In a 0.5-1 round bottom flask, which was equipped according to Example 1, was a suspension of 20090 9 = 22.2 ol methyl glycolate and 35.7 g = 095 mol submitted plus 10% sodium cyun.

A solution of 77.3 g = 0.5 mol was gradually added with stirring # -Chloroacetophenone in 45.3 g = 0.5 mol of glycolic acid methyl ester.

After a reaction time of 15/4 hours at 80 ° C., the reaction was complete completed.

The crude product, which was solid at room temperature, was treated with 70 g of acetonitrile added, heated to 50 ° C and pressure filtered. After concentrating the filtrate in Rotary evaporator remained 129.4 9 of a reddish-brown colored crystalline Mass from which, when recrystallized from ethanol, 47.8 g of pure 3-phenacyloxazolidine-dione (S, 4) could be isolated, corresponding to a yield of 43.7% of theory. Th .; Mp: 128 up to 130 ° C.

% C: 59.9 (Th: 60.2); % H: 4.1 (Th: 4.1)% N: 6.3 (Th: 6.4)

Claims (5)

Claims 1. Process for the preparation of N-substituted oxazolidinedione- (2,4) of the general formula (JI) where n and m have the meanings zero or 1, A is the same or different and H, CH3 or C 2H5, R² and R 3 are hydrogen or a saturated or unsaturated alkyl radical with up to 4 carbon atoms, or may also be halogen-substituted or an aryl, aralkyl or cycloalkyl radical with 6 to 10 carbon atoms, and R1 denotes a group Y or a Cr group Z, where Y is a saturated or unsaturated alkyl radical with up to 4 carbon atoms or an alkoxy radical of gloicien Is carbon number, and these radicals can be substituted by halogen, cyano, trihaloyenmethyl or Alkoi, while Z is an aryl, aryloxy, thioaryl, aralkyl, aralkyloxy or cycloalkyl radical, each one or more times by halogen, cyano , Nitro, trihalomethyl or alkoxy may be ring-substituted by reacting an isocyanate of the general formula (III) O = C = N- (CA) n- (CO) m -R¹ (III) with an α-hydroxycarboxylic acid ester of the general formula (iu) in which R4 denotes an alkyl radical with 1 to 4 carbon atoms, characterized in that the isocyanate (III) is obtained from alkali metal cyanate and an organohalide of the general formula (V) X- (CA2) n- (CO) m-R¹ (V ) in which X ~ Cl, Br or J is generated in situ in the presence of the α-hydroxycarboxylic acid ester (IV), the molar ratio of (V): (IV) being in the range from 2: 1 to 1:10, the The reaction temperature is 20 to 200 ° C and one works in Anodor Ahwesenhnit oines polar aprotic solvent. 2. The method according to claim 1, characterized in that the molar ratio Alkali cyanate to organ halide (V) is 1: 1 to 2: 1. 3. The method according to claim 1, characterized in that the α-hydroxycarboxylic acid ester is a glycolic or lactic acid ester. 4. The method according to claim 1, characterized in that in the Procedure in a solvent as such excess α-hydroxycarboxylic acid ester (IV) is used. 5 N-substituted oxazolidine-diones (2,4) of the formula in which n = 0 or 1, m = 1 and R1 = alkyl or alkyl with 1 to 4 carbon atoms, R2 and R3 denote hydrogen, or a saturated or unsaturated alkyl radical with up to 4 carbon atoms, which also May be halogen-substituted, or an aryl, aralkyl or cycloalkyl rust with 6 to 10 carbon atoms, and A is identical or different and represents H, CH3 or C2H5.