JPH0948769A - Production of 2,4-oxazolidindione compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To easily obtain in high yield without the need of using any expensive alkali metal compound, the subject compound useful as an intermediate for photographic yellow couplers or medicines. SOLUTION: This compound, a 2,4-oxazolidindione, is expressed by formula I (R1 and R2 are each H, an alkyl, phenyl, benzyl or a heterocyclic group), e.g. 5,5-dimethyl-2,4-oxazolidindione. The compound of formula I is obtained by reaction of a mixture of a 2-hydroxycarboxylic ester or 2-hydroxycarboxylic acid amide of formula II (X is an alkoxyl or amino) (e.g. glycolic acid, lactic acid) and urea in the presence of, as a catalyst, a metallic simple substance such as copper or beryllium or its compound at 100-250 deg.C. It is preferable that the amount of the compound of formula II to be used is 1-5mol per mol of the urea.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing 2,4-oxazolidinediones. The 2,4-oxazolidinediones are important substances as, for example, an intermediate for producing a yellow coupler for photography or an intermediate for producing a pharmaceutical.

[0002]

2. Description of the Related Art As a method for producing 2,4-oxazolidinediones, 2,2-oxazolidine is conventionally prepared by heating 2-hydroxycarboxylic acid esters and urea in ethanol in the presence of an equivalent amount of sodium ethylate. Method for obtaining sodium salt of diones and neutralizing the same with acid to obtain free 2,4-oxazolidinediones [Journal of American Chemical Society (JACS) 63: 2376-23]
79 (1941)], 2-hydroxycarboxylic acid amides and carbonic acid esters are heated in an alcohol in the presence of an equivalent amount of sodium alcoholate to obtain a sodium salt of 2,4-oxazolidinediones. A method of neutralizing to obtain free 2,4-oxazolidinediones [Journal of
American Chemical Society (JACS) Volume 67
522-523 (1945)], heating 2-hydroxycarboxylic acid esters and alkali cyanate in alcohol.
A method has been proposed in which an alkali metal salt of 2,4-oxazolidinediones is obtained and neutralized with an acid to obtain free 2,4-oxazolidinediones (JP-A-59-216882).

[0003]

All of the conventional methods for producing 2,4-oxazolidinediones require an equivalent amount of an expensive alkali metal compound. Moreover, for this reason, the 2,4-oxazolidinediones obtained by the reaction are alkali metal salts, and complicated operations such as neutralization and desalting are necessary to obtain free 2,4-oxazolidinediones. is there. The object of the present invention is, without the use of expensive alkali metal compounds,
It is intended to provide a method for easily producing 4-oxazolidinediones in a high yield.

[0004]

Means for Solving the Problems The present inventor has conducted extensive studies on a method for producing 2,4-oxazolidinediones having the above-mentioned problems, and as a result, 2-hydroxycarboxylic acid esters or 2-hydroxycarboxylic acid By reacting amides with urea at a temperature of 100 to 250 ° C.,
The present invention has been completed by finding that 2,4-oxazolidinediones can be easily obtained in high yield.

That is, the present invention is characterized in that 2-hydroxycarboxylic acid esters or 2-hydroxycarboxylic acid amides represented by the general formula (I) are reacted with urea at a temperature of 100 to 250 ° C. 2,4-represented by the general formula (II)
A method for producing oxazolidinediones,

Embedded image (R ₁ and R ₂ are a hydrogen atom, a lower alkyl group, a phenyl group, a benzyl group or a heterocyclic group, X is a lower alkoxy group or an amino group, and R ₁ and R ₂ may be the same or different),

Embedded image (R ₁ and R ₂ are a hydrogen atom, a lower alkyl group, a phenyl group, a benzyl group or a heterocyclic group, and R ₁ and R ₂ may be the same or different) and copper, beryllium or calcium is used as a catalyst. , Barium, zinc, cadmium,
One or more metal elements or compounds selected from aluminum, titanium, tin, lead, vanadium, antimony, bismuth, chromium, molybdenum, tellurium, manganese and iron are used.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The reaction of the present invention is usually carried out by adding a catalyst to a mixed solution of 2-hydroxycarboxylic acid esters or 2-hydroxycarboxylic acid amides and urea, and then heating. Examples of 2-hydroxycarboxylic acid esters or 2-hydroxycarboxylic acid amides used as a raw material include glycolic acid, lactic acid, 2-hydroxybutyric acid, 2-hydroxyisobutyric acid, 2-hydroxyvaleric acid, 2-hydroxyhexanoic acid, Lower alkyl esters or amides of 2-hydroxycarboxylic acids such as mandelic acid, 2-hydroxy-3-phenylpropionic acid, and 2- (2-thienyl) glycolic acid are included.

The ratio of the starting 2-hydroxycarboxylic acid ester or 2-hydroxycarboxylic acid amide to urea is 1 mol of 2-hydroxycarboxylic acid ester or 2-hydroxycarboxylic acid amide to 1 mol of urea. It is desirable to be in the range of up to 5 mol. When the molar ratio of 2-hydroxycarboxylic acid esters or 2-hydroxycarboxylic acid amides to urea is less than 1, the selectivity of 2,4-oxazolidinediones decreases due to a side reaction of urea itself. When the molar ratio of 2-hydroxycarboxylic acid ester or 2-hydroxycarboxylic acid amide to urea is larger than 5, the amount of 2-hydroxycarboxylic acid ester or 2-hydroxycarboxylic acid amide recovered and recycled increases. Therefore, it is not economically preferable.

The reaction of the present invention proceeds without using a catalyst by setting the reaction temperature to 100 ° C. or higher, but it is preferable to use a catalyst. The catalyst is copper, beryllium,
Calcium, barium, zinc, cadmium, aluminum, titanium, tin, lead, vanadium, antimony, bismuth, chromium, molybdenum, tellurium, manganese and iron selected from one or more metals alone or compounds are used, but are not particularly limited. Generally, this metal powder, metal plate, oxide, hydroxide, inorganic salt, carbonate, basic carbonate, organic acid salt or the like is used. Further, these catalysts are organic compounds existing in the reaction system, for example, 2-hydroxycarboxylic acid esters, 2-hydroxycarboxylic acid amides, 2,
Also used are those that have reacted with 4-oxazolidinediones, urea, ammonia and the like. These catalysts may be used alone or in combination with two or more. Further, it can be used by mixing with a compound or carrier which is inactive to the reaction, or by supporting them on these. The amount of the catalyst used is not particularly limited, but usually 0.0001 to 10 mol of these metal simple substances or compounds relative to 1 mol of urea,
Preferably, the amount used is in the range of 0.001 to 1 mol.

In the present invention, the reaction is usually carried out in an excess system of 2-hydroxycarboxylic acid esters or 2-hydroxycarboxylic acid amides. Therefore, if the starting 2-hydroxycarboxylic acid ester or 2-hydroxycarboxylic acid amide has a low melting point and a low viscosity, a solvent is not particularly necessary, but if the melting point and the viscosity are high, a solvent is used. It is desirable to do. The type of solvent is not particularly limited as long as it is inert and soluble in the reaction system, but cyclic carbonate, aromatic hydrocarbon, ether and the like are preferably used. The amount of the solvent used is not particularly limited, but usually urea 1
The amount is in the range of 0.1 to 10 mol based on mol.

The reaction of the present invention is carried out by keeping a mixture of 2-hydroxycarboxylic acid esters or 2-hydroxycarboxylic acid amides, urea and a catalyst at the reaction temperature, and at the same time removing ammonia produced from the reaction mixture. Be seen. In order to remove ammonia, a method of introducing an inert gas into the reaction solution during the reaction during the reaction is also effective, but the reaction may be performed under the reflux of the raw material or solvent instead of the inert gas. The way to do it is more effective. When the raw material or solvent has a high boiling point, it is desirable to carry out reflux under reduced pressure. The amount of reflux of the raw material or the solvent is 1 to 100 mol with respect to 1 mol of the produced ammonia.

The reaction temperature in the present invention is 100 to 25.
In the range of 0 ° C, 120 to 200 ° C is particularly preferable. When the reaction temperature is too low, the reaction rate is slow, and when it is too high, the amount of side reaction increases. The reaction time varies depending on the type of the 2-hydroxycarboxylic acid ester or 2-hydroxycarboxylic acid amide as the raw material, the type and amount of the catalyst, the reaction temperature and the reflux amount of the raw material or the solvent, but usually 0.5 to 20 It's time. After completion of the reaction, the 2,4-oxazolidinediones produced by the reaction can be easily separated and recovered from the reaction solution by a conventional method such as distillation. The reaction of the present invention can be carried out by either a batch method or a continuous method.

[0012]

Next, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples.

Example 1 Methyl 2-hydroxyisobutyrate (23.63) was placed in a 50 ml three-necked flask equipped with a stirrer, a reflux condenser and a thermometer.
g (0.200 mol), urea 6.01 g (0.100 mol) and zinc oxide 0.30 g were added, and the mixture was stirred at normal pressure with stirring 1
The mixture was heated to reflux at 40 to 157 ° C. After the reaction for 6 hours, the reaction liquid was cooled to obtain 27.05 g of a reaction liquid. When the composition of the reaction solution was analyzed by liquid chromatography, 12.19 g of unreacted methyl 2-hydroxyisobutyrate and 5,5-dimethyl produced
The amount of the -2,4-oxazolidinedione was 11.65 g. This result shows that the conversion rate of methyl 2-hydroxyisobutyrate is 51.6% against the theoretical value of 50.0%, and the yield of 5,5-dimethyl-2,4-oxazolidinedione based on the charged urea is It is 90.2%.

Example 2 A reactor similar to that used in Example 1 was charged with 12.89 g (0.125 mol) of 2-hydroxyisobutyric acid amide and 6.01 g of urea.
(0.100 mol) 0.30 g of zinc oxide and 10.81 g (0.100 mol) of anisole as a solvent were added, and the mixture was heated to reflux at 155 to 168 ° C. under normal pressure and stirring. 1
After the reaction for 0 hour, the reaction liquid was cooled to obtain 26.13 g of a reaction liquid. When the composition of the reaction solution was analyzed by liquid chromatography, 2.91 g of unreacted 2-hydroxyisobutyric acid amide,
Produced 5,5-dimethyl-2,4-oxazolidinedione 1
It was 1.30 g. This result shows that the conversion rate of 2-hydroxyisobutyric acid amide is 77.4 compared to the theoretical value of 80.0%.
%, And the yield of 5,5-dimethyl-2,4-oxazolidinedione based on the charged urea was 87.5%.

Comparative Examples 1-2, Examples 3-5 Example 1 except that the catalyst, reaction temperature and reaction time were changed.
The reaction was carried out in the same manner as in, and the effects of the reaction temperature and the catalyst were compared. The results are shown in Table 1.

[0016]

[Table 1] Catalyst Temperature Time Reaction solution Reaction composition (g) HBM Urea standard (℃) (Hr) Amount (g) HBM Oxa conversion (%) Oxa yield (% ) Comparative Example 1 None 80 10 29.78 23.63 0.0 0 0 Example 3 None 150 3 29.04 20.54 3.10 13.1 24.0 Comparative Example 2 PbO 80 10 29.87 23.44 0.19 0.8 1.5 Example 4 PbO 120 10 28.99 19.56 4.13 17.2 32.0 Example 5 PbO 150 3 27.32 11.41 12.18 51.7 94.3 HBM: 2- Methyl hydroxyisobutyrate Oxa: 5,5-dimethyl-2,4-oxazolidinedione

Examples 6 to 8 Lead oxide was used as a catalyst, and 10.21 g of propylene carbonate was used as a solvent.
(0.100 mol) was used and the reaction was performed in the same manner as in Example 2 except that the reaction pressure, reaction temperature and reaction time were changed, and the reaction temperatures were compared. Table 2 shows the results.

[Table 2] Pressure Temperature Time Reaction solution Composition of reaction solution (g) HBD urea standard mmHg (℃) (Hr) amount (g) HBD Oxa conversion rate (%) Oxa yield (% ) Example 6 15 120 10 28.87 11.11 2.04 13.7 15.8 Example 7 50 150 8 26.32 2.59 11.83 79.9 91.6 Example 8 145 180 3 26.20 2.49 12.10 80.7 93.7 HBD: 2-hydroxyisobutyric acid amide

Examples 9 to 49 In the same reactor as in Example 1, 35.44 g (0.300 mol) of methyl 2-hydroxyisobutyrate and 6.01 g of urea were added.
(0.100 mol) and 0.15 g of various catalysts,
Heat and reflux for 3 hours at 140 to 157 ° C. under normal pressure and stirring,
The catalyst species were compared. The results are shown in Table 3.

[0019]

Table 3 Reaction solution Reaction solution composition (g) HBM urea standard catalyst amount (g) HBM Oxa conversion rate (%) Oxa yield (% ) Example 9 ZnO 39.88 24.84 10.87 29.9 84.2 Example 10 MgO 41.17 32.60 2.93 8.0 22.7 Example 11 CaO 39.72 24.29 11.12 31.5 86.1 Example 12 PbO 39.54 23.08 12.29 34.9 95.2 Example 13 Pb O ₂ 39.51 23.22 12.23 34.5 94.7 Example 14 CuO 39.58 23.31 11.89 34.2 92.1 Example 15 SnO 39.63 22.96 11.72 33.5 90.8 Example 16 Fe ₂ O ₃ 40.38 29.03 6.73 18.1 52.1 Example 17 Co ₂ O ₃ 41.12 32.56 2.98 8.1 23.1 Example 18 Tl ₂ O ₃ 39.97 26.99 8.44 23.8 65.4 Example 19 Al ₂ O ₃ 40.01 26.80 8.69 24.4 67.3 Example 20 Mn O ₂ 39.86 24.94 10.55 29.6 81.7 Example 21 Zr O ₂ 41.14 32.45 3.03 8.4 23.5 Example 22 Ti ₂ O ₃ 41.17 32.23 3.25 9.1 25.2 Example 23 Si O ₂ 41.23 32.00 3.50 9.7 27.1 Example 24 V ₂ O ₅ 39.95 25.01 10.30 29.4 79.8 Example 25 Sb ₂ O ₃ 40.51 29.62 5.85 16.4 45.3 Example 26 BeO 40.58 29.26 6.29 17.4 48.7 Example 27 Mo ₂ O ₃ 39.87 24.96 10.78 29.6 83.5 Example 28 NiO 41.2 5 32.04 3.46 9.6 26.8 Example 29 BaO 40.44 28.77 6.60 18.8 51.1 Example 30 WO ₃ 40.55 29.73 5.75 16.1 44.5 Example 31 Ag ₂ O 40.49 29.32 6.24 17.3 48.3 Example 32 Ta ₂ O ₅ 41.13 31.66 3.80 10.7 29.4 Example 33 Te O ₂ 39.92 24.96 10.38 29.6 80.4 Example 34 Bi ₂ O ₃ 39.66 23.92 11.59 32.5 89.8 Example 35 CdO 39.98 25.17 10.26 29.0 79.5 Example 36 Zn powder 40.06 26.27 9.53 25.9 73.8 Example 37 ZnCl ₂ 39.98 25.08 10.34 29.2 80.1 Example Example 38 Cr ₂ O ₃ 40.15 26.53 8.96 25.1 69.4 Example 39 SrSO ₄ 41.09 30.90 4.56 12.8 35.3 Example 40 Pb powder 39.44 23.40 12.34 34.0 95.6 Example 41 PbCl ₂ 39.72 24.24 11.03 31.6 85.4 Example 42 * Basic lead carbonate 39.56 23.53 11.76 33.6 91.1 Example 43 ** n-Bu ₂ SnO 39.41 23.65 11.99 33.3 92.9 Example 44 ** Ti (OBu) ₄ 40.01 25.68 9.80 27.5 75.9 Example 45 *** DBU 40.11 26.04 9.45 26.5 73.2 Example 46 Pb Sheet 39.53 24.24 11.68 31.6 90.5 * Example 42 Basic lead carbonate: 2PbCO ₃ Pb (OH) ₂ ** Bu: Butyl group *** DBU: Diazabicycloundece N

Examples 47 to 51 Various 2-hydroxycarboxylic acid ester species were prepared in the same manner as in Example 1 except that 0.15 g of lead oxide was used as a catalyst and the solvent (anisole), reaction temperature and reaction time were changed. The reaction was carried out. The results are shown in Table 4.

[0021]

[Table 4] Implementation solvent Temperature Time Reaction solution Reaction solution composition (g) Ester urea Reference example No. (g) (℃) (Hr) Amount (g) Ester Oxa conversion rate (%) Oxa yield (% ) 47 None 165 1.5 24.87 10.10 9.81 51.5 97.1 48 None 160 2.0 28.65 11.75 10.85 50.3 94.3 49 10.81 170 1.0 47.62 16.60 16.28 50.1 91.9 50 16.22 165 1.5 49.38 9.58 17.72 67.1 92.7 51 13.52 165 1.5 38.14 4.20 16.65 80.4 90.9 (ester used) Example 47 : Ethyl glycolate 20.82 g (0.20 mol) Example 48: Ethyl lactate 23.63 g (0.20 mol) Example 49: Methyl mandelate 33.24 g (0.20 mol) Example 50: Ethyl phenyl lactate 29.14 g (0.15 mol) Example 51: Methyl 2- (2-Cenyl) glycolate 21.53 g (0.125 mol)

[0022]

EFFECTS OF THE INVENTION According to the method of the present invention, 2,4-oxazolidinediones are converted from 2-hydroxycarboxylic acid esters or 2-hydroxycarboxylic acid amides and urea without using an expensive alkali metal compound. It can be easily manufactured with high yield.

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Claims (2)

[Claims] 1. A general formula characterized by reacting 2-hydroxycarboxylic acid esters or 2-hydroxycarboxylic acid amides represented by the general formula (I) with urea at a temperature of 100 to 250 ° C. A method for producing 2,4-oxazolidinediones represented by (II). Embedded image (R ₁ and R ₂ are a hydrogen atom, a lower alkyl group, a phenyl group, a benzyl group or a heterocyclic group, X is a lower alkoxy group or an amino group, and R ₁ and R ₂ may be the same or different), [Chemical 2] (R ₁ and R ₂ are a hydrogen atom, a lower alkyl group, a phenyl group, a benzyl group or a heterocyclic group, and R ₁ and R ₂ may be the same or different). 2. Copper, beryllium, calcium, barium,
2. The catalyst according to claim 1, wherein at least one metal element or compound selected from zinc, cadmium, aluminum, titanium, tin, lead, vanadium, antimony, bismuth, chromium, molybdenum, tellurium, manganese and iron is used as a catalyst.
Process for producing 4-oxazolidinediones.