JPH0588702B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Field of Application] The present invention relates to a method for synthesizing glycolamide or an analog thereof. Glycolamide or its analog provided by the present invention is a substrate of acylamidase (Honma, "Pseudomonas aeruginosa and its infections", 43-
46 pages (Bunkodo, 1975)) or intermediates for the production of herbicides (U.S. Pat. No. 3,399,988,
DE-OS No. 2201432 and DE-OS No. 2647568
(No.) will be used effectively. [Prior Art] A method for synthesizing glycolamide analogs from α-halogen acid amide is disclosed in Japanese Patent Publication No. 35162/1983. [Problems to be Solved by the Invention] In the above method, a halogen atom at the α-position is converted to acetoxy, and then the ester is hydrolyzed to obtain a glycolamide analog. It requires potassium, requires heating operations to reach a reaction temperature of 100°C or higher, and requires a long reaction time. Furthermore, an improved method of this method was published in Japanese Patent Application Laid-Open No. 55-105624.
Disclosed in the issue. Although this method eliminates the need for an excessive amount of acetate to produce acetoxy, it still requires heating operations to reach a reaction temperature of 100°C or higher, and the reaction time is 4 hours or more. I need it. In addition, a special quaternary ammonium salt must be added, which is very complicated. Therefore, an object of the present invention is to provide a method for producing glycolamide or its analogs, which allows easy setting of reaction conditions and shortens reaction time. [Means for Solving the Problems] The present invention that achieves the above object is based on the following method. That is, (1) General formula

[Formula, R ₁ , R ₂ , and X may be the same or different and each represents hydrogen, lower alkyl, lower alkenyl, alkynyl, aralkyl, or aryl group, and R ₁ and _R Alternatively, R ₁ and X may be combined to form a cyclic structure. In addition, R ₁ , R ₂ ,
may be a substituent containing nitrogen, oxygen or sulfur. ) A method for producing glycolamide or its analogues represented by the general formula

[Chemical formula] (In the formula, R ₁ , R ₂ , and X are the same as those in the above formula (), and Y represents a halogen atom.) is used as a starting compound, and this is reacted with aryl methyl alcohol in the presence of a base. By this,
general formula

This is a production _method characterized by obtaining _the following formula and debenzylating it: As the aryl methyl alcohol, benzyl alcohol or 4-methoxyphenyl methyl alcohol is preferably used. In addition, as a base, sodium hydride, sodium metal,
Preference is given to using potassium carbonate, triethylamine or pyridine. The α-allylmethoxy compound of the present invention represented by the above formula () is synthesized by reacting the α-halogen compound of the above formula () with aryl methyl alcohol under basic conditions. Examples of organic solvents used include tetrahydrofuran, diethyl ether, dioxane, dimethylformamide,
Dimethyl sulfoxide, benzene or toluene are suitable. Further, as the aryl methyl alcohol, benzyl alcohol or 4-methoxyphenyl methyl alcohol is preferable because the subsequent deallyl methylation is easy.
Further, as the base, sodium hydride, sodium metal, potassium carbonate, triethylamine or pyridine is preferable. If these alcohols or bases are used, heating operation becomes unnecessary. This reaction is an exothermic reaction and does not require heating, but even if heated, temperatures below 50°C are sufficient. Moreover, this reaction is completed in a short time (within 1 hour). The desired product is recovered from the reaction mixture in conventional manner. For example, the desired product can be obtained by adding water to the reaction mixture, extracting with a suitable organic solvent such as ethyl acetate, distilling off the solvent from the extract, and purifying the residue by recrystallization or column chromatography. can get things. Furthermore, in order to obtain glycolamide or its analogue () from the α-allyl methoxy compound (), α-allyl A hydrogenation reaction of the methoxy compound () may be performed. Ethanol, methanol, acetic acid, tetrahydrofuran, dimethylformamide, and benzene can be used as the solvent. As before, this reaction does not require any heating operation and is completed within 1 hour at room temperature. The metal catalyst is then removed by filtration, and the filtrate is concentrated under reduced pressure to obtain the desired glycolamide and its analogs (). The deallyl methylation reaction can also be carried out using the metal catalyst for hydrogenation and cyclohexene or cyclohexadiene. In addition, the deallyl methylation reaction can also be performed using sodium or lithium metal (the solvent is ammonia, ethanol, etc.), or using a Lewis acid such as boron triborate, boron tribromide, or trifluoroacetic acid. By this,
Glycolamide or its analogue () can also be obtained from the α-allylmethoxy compound (). Next, the present invention will be explained in more detail with reference to Examples. Example 1

[Formula] 2.70g of sodium hydride under nitrogen atmosphere
6.00 ml (57.98 ml) of benzyl alcohol and 5.00 g (53.5 mmol) of 2-chloroacetamide were added to a 75 ml solution of dry tetrahydrofuran (113 mmol) at room temperature, and the mixture was reacted at 40°C for 1 hour. The reaction solution was heated to 20°C, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and concentrated under reduced pressure to obtain a residue. By recrystallizing this from ethanol, 8.66 g (52.4 mmol) of 2-benzyloxyacetamide was obtained. 43.3 ethanol to 8.66 g (52.4 mmol) of the amide
ml, add 0.043 ml of 36% hydrochloric acid, further add 866 mg of 10% palladium carbon catalyst, and add 30 ml of 36% hydrochloric acid under hydrogen atmosphere.
Allowed to react for minutes. 21.6 ml of methanol was added to the reaction solution, and insoluble matter was removed by filtration. The filtrate was concentrated under reduced pressure and the resulting residue was recrystallized with ethanol to yield 3.89 g of glycolamide in the form of white needle-like crystals.
(51.8 mmol) was obtained. NMR (δppm, CD ₃ OD) 3.97 (s, 2H), 4.77 (s, 3H) IR (νcm ^-1 , KBr) 3360, 3200, 1680 Example 2

〔Effect of the invention〕

According to the present invention, a novel method for producing glycolamide or an analog thereof is provided. Further, according to the present invention, there is no need to use an excessive amount of reaction reagents, and there is no need to add a special quaternary ammonium salt, and reaction conditions can be easily set. Furthermore, there is no need to set the reaction at a high temperature such as reflux conditions, and the reaction can proceed sufficiently at room temperature, and the reaction time can also be shortened.

Claims (1)

[Claims] 1 General formula [Chemical formula] (In the formula, R ₁ , R ₂ , and R ₁ and R ₂ or R ₁ and X may be combined to form a cyclic structure. Note that R ₁ , R ₂ ,
may be a substituent containing nitrogen, oxygen or sulfur. ) A method for producing glycolamide or its analogs represented by the general formula: (wherein R ₁ , R ₂ , and X are the same as in the above formula (), and Y represents a halogen atom. ) is used _as a starting compound, and by reacting it with aryl methyl alcohol in the presence _of a base, the general formula: A method for producing a glycolamide or an analogue thereof, characterized in that the obtained product is debenzylated. 2. The manufacturing method according to claim 1, wherein benzyl alcohol or 4-methoxyphenyl methyl alcohol is used as the aryl methyl alcohol. 3. The manufacturing method according to claim 1 or 2, wherein sodium hydride, sodium metal, potassium carbonate, triethylamine or pyridine is used as the base.