KR900005698B1 - Process for preparing - oxyketon-dioxolane derivatives - Google Patents

Abstract

Cpds. of formula (I) are prepd. by reacting a cpd. of formula (II) with a cpd. of formula (III) in the presence of acid catalyst and organic solvent. In the formulas, R= C1-4 alkyl; X= halogen; Y= reactive ester or halogen; Z= H, lower alkylcarbonyl, alkylcarbamyl, arylcarbamyl or arylcarbonyl. (I) are useful as intermediates in the prepn. of medicines or agricultural chemicals.

Description

Method for preparing dioxolane derivatives of α-oxyketone

The present invention relates to an easy, new and advanced process for the preparation of compounds represented by the following general formula (I) which can be usefully used as intermediates for medicine and pesticides.

Wherein X represents substituted with up to 3 halogens, Y represents a reactive ester, halogen and Z represents H, lower alkylcarbonyl, arylcarbonyl, arylcarbamyl or alkylcarbamyl.

In general, α-hydroxyketone cannot be acetylated. However, the present inventors can easily obtain the compound of the general formula (I) with high yield and good purity by carrying out the trans-acetylation reaction by adding an acid as a catalyst to the compound of the general formula (II) and the general formula (III) in a suitable solvent. The discovery of surprising facts has led to the completion of the present invention.

In the compound of formula II, X, Y and Z are as described above, R means C ₁ -C ₄ alkyl, C ₁ -C ₄ alkyl is methyl, ethyl, propyl, butyl and the like, isomer thereof Also includes.

In the present invention, the reaction solvent is selected from solvents such as dichloromethane, chloroform, ethyl acetate, THF, DMF, dioxane and the like, and non-reactive solvents having substituents on the benzene ring such as benzene, toluene and xylene. Acids used as catalysts generally refer to strong acids, for example toluenesulfonic acid, methanesulfonic acid, hydrochloric anhydride, sulfuric acid and the like.

Accordingly, an object of the present invention relates to a novel process for preparing the compound of formula (I) with high purity and high yield by reacting the compound of formula (II) with the compound of formula (III) in the presence of an acid catalyst.

Structural formula (II) compounds used as starting materials in the present invention are novel materials.

Accordingly, another object of the present invention relates to a general formula (II) compound and a preparation method thereof. Compounds in which Z is hydrogen in the compound of formula (II) are prepared by reacting the following compound of formula (IV) which is a known compound with the following compound of formula (V) and lower alcohol (C ₁ -C ₄ ) in the presence of a base. .

In the formula, X is as described above, A means a substituent such as hydrogen, halogen, carboxylic acid or sulfonic acid, B means O, (OAc) ₂ , Cl ₂ and the like. Therefore, to provide a general formula (II) compound and its preparation method. As the base, metal alkoxides of lower alcohols, hydroxide bases such as sodium hydroxide and potassium hydroxide, and organic bases such as triethylamine are used.

In the case where Z is not hydrogen in the compound of the general formula (II), esterification or carbamylation reaction is carried out in a conventional manner to obtain the corresponding ester or carbamylated derivatives of the compound of the general formula (II).

In order to explain the invention in more detail, the following examples are provided.

These examples are merely illustrative, and these examples do not limit the scope of the present invention.

Example 1

Dissolve 40 g of potassium hydroxide in 300 ml of methanol, lower the temperature to 0 ° C., dissolve 38 g of 1- (2,4-dichlorophenyl) ethanol in 100 ml of methanol, stand for 30 minutes, and then stir for 30 minutes. -58 g of iodine-sobenzoic acid was added slowly for 30 minutes, then the temperature was raised to 20 ° C. and the stirring was continued for 36 hours. After all methanol was removed under reduced pressure, it was dissolved in 200 ml of dichloromethane and washed three times with 100 ml of water. The organic layer was dried over anhydrous sodium sulfate, and then the solvents were all removed under reduced pressure. Then, 43.6 g (crude yield 85%) of 2- (2,4-dichlorophenyl) -2,2-dimethoxy-ethanol was obtained as a crude product. Obtained as a syrupy material.

Example 2

25 g of 2- (2,4-dichlorophenyl) -2,2-diethoxy-ethanol of Example 1 was dissolved in 100 ml of anhydrous dichloromethane and 20 ml of triethylamine, and 19 g of 4-nitrobenzoate at 30 ° C. After stirring for 30 minutes at 0 ° C. for 30 minutes and further stirring at 20 ° C. for 2 hours, the reaction solution was washed with 100 ml of water, and the organic layer was treated with anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to remove methanol. Recrystallization at gave (2- (2,4-dichlorophenyl) -2,2-dimethoxy) ethyl 4-nitrobenzoate in a yield of 34 g (85%).

Melting point: 127-129 ° C.

Example 3

To 200 ml of toluene, 1 g of toluenesulfonic acid and 12 g of 3-chloro-1,2-propanediol and 40 g of (2- (2,4-dichlorophenyl) -2,2-dimethoxy) ethyl 4-nitrobenzoate Methanol was removed while stirring under reflux for 1 hour, and the reaction was cooled. After the reaction was cooled, 100 ml of ethyl acetate was added and extracted. Then, the extract was washed twice with 100 ml of aqueous sodium hydrogen carbonate solution and then twice with 100 ml of water. After drying over anhydrous magnesium hydroxide, all solvent was removed and recrystallized from methanol to obtain 40.6 g (91%) of cis + trans-2- (2,4-dichlorophenyl) -2- (4-nitrobenzenecarbonyloxymethyl) 4-chloromethyl-1,3-dioxolane was obtained.

Melting point: 101-102 ° C.

Example 4

Dissolve 5.15 g of 2- (2,4-dichlorophenyl) -2,2-dimethoxyethanol in 30 ml of dichloromethane, add catalytic amount of triethylamine, add 2.5 ml of phenyl isocyanate and stir at room temperature for 4 hours 30 minutes. Then, dichloromethane was removed and recrystallized from methanol to give a yield of 6.88 g (93%) of 2- (2,4-dichlorophenyl) -2,2-dimethoxyethyl-N-phenylcarbamate.

Melting Point: 100-101 ℃

Example 5

Cis + trans-2- (2,4-dichlorophenyl) -2- (4-phenylcarbamyloxy methyl) -4-bromomethyl-1,3-dioxolane was prepared in the same manner as in Example 3. (oil).

Claims (6)

The following general formula (II) compound is reacted with the following general formula (III) compound in an organic solvent in the presence of an acid catalyst, to prepare the following general formula (I) compound.

In the above formula. R stands for C ₁ -C ₄ alkyl, X stands for substituted by up to 3 halogens, Y stands for reactive ester, halogen, 2 is H, lower alkylcarbonyl, alkylcarbamyl, or arylcarbamyl , Arylcarbonyl is indicated. The method of claim 1 wherein the strong acid is used as the acid catalyst. The process of claim 1 wherein the reaction is carried out in a non-reactive solvent. General Structural Formula (II) Compound

Wherein R represents lower (C ₁ -C ₄ ) alkyl, X represents substituted with up to 3 halogens, and Y represents a reactive ester. Halogen, and 2 represents lower alkylcarbonyl, arylcarbonyl, alkylcarbamyl or arylcarbamyl. A method of preparing the following general formula (II) compound by reacting the following general formula (IV) compound with the following general formula (V) compound and lower (C ₁ -C ₄ ) alcohol in the presence of a base.

Wherein R represents lower (C ₁ -C ₄ ) alkyl, X represents substituted with up to 3 halogens, Z represents H, lower alkylcarbonyl, arylcarbonyl, alkylcarbamyl or arylcarbamyl Indicates. A means a substituent such as hydrogen, halogen, carboxylic acid or sulfonic acid, B means O, (OAc) ₂ , Cl, and the like. The method according to claim 5, wherein the reaction is carried out in the presence of a base such as an organic amine, an alkali metal hydroxide or an alkali metal alkoxide.