JP2606935B2 - Method for producing amide ester compound - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial application field) The present invention relates to a method for producing an amide ester compound from an amide carboxylic acid compound having a group represented by the formula:

(Problems to be Solved by the Prior Art and the Invention) Conventionally, an amide ester compound having both an amide bond and an ester bond in one molecule has been replaced with an amide carboxylic acid compound having both an amide bond and a carboxyl group in one molecule. It is produced by adding a mixed solution of methanol / dichloroethane / sulfuric acid and performing an esterification reaction. However, this production method has an extremely low yield of about 20% of the amide ester compound as a product.

(Means for Solving the Problems) As a result of intensive studies to solve the above problems, the present inventors have found a method for producing an amide ester compound in high yield, and have completed the present invention. Reached.

That is, the present invention A method for producing an amide ester compound characterized by reacting an amide carboxylic acid compound having a group represented by and a halogen-containing compound in a polar aprotic solvent in the presence of an alkali metal compound or an alkaline earth metal compound. is there.

 Hereinafter, the present invention will be described in detail.

The amide carboxylic acid compound used as a raw material in the present invention includes: As long as it is a compound having a group represented by, a known compound is employed without any limitation.

The amide carboxylic acid compound suitably used in the present invention is represented by the following general formula.

However, R ¹ , R ² , R ³ and R ⁴ are the same or different hydrogen atoms or monovalent hydrocarbon groups, or R ¹ and R ³ form a ring, and R ⁵ and R ^{5 6} is the same or different divalent hydrocarbon group or forms a ring, R ⁷ is a divalent aromatic hydrocarbon group or a divalent unsaturated heterocyclic group which may have a substituent, and R ⁷ is a monovalent hydrocarbon group which may have a substituent. Or 1
R ⁸ and R ⁹ are the same or different hydrogen atoms or monovalent hydrocarbon groups, A norbornylidene group which may have a substituent, or
Adamantylidene group.

In the above formula, examples of the monovalent hydrocarbon group represented by R ¹ , R ² , R ³ , R ⁴ , R ⁷ , R ⁸ and R ⁹ include an alkyl group, an alkenyl group, an alkynyl group and an aryl group. Can be The ring formed by R ¹ and R ³ includes a cyclohexane ring. In the above formula, the divalent hydrocarbon group represented by R ⁵ and R ⁶ is an alkylidene group or an arylidene group. When R ⁵ and R ⁶ form a ring, a benzene ring may be mentioned. further Examples of the divalent aromatic hydrocarbon group represented by are divalent groups derived from aromatic hydrocarbons such as a benzene ring, a naphthalene ring, and a phenanthrene ring. Examples of the divalent unsaturated heterocyclic group include And divalent groups derived from unsaturated heterocycles such as a pyrrole ring, a pyridine ring, a quinoline ring, an isoquinoline ring, a furan ring, a benzofuran ring, a pyran ring, a thiophene ring and a benzothiophene ring. Further, specific examples of the monovalent heterocyclic group represented by R ⁷ include the aforementioned 1 derived from an unsaturated heterocyclic ring described in the definition of
In addition to the monovalent groups, monovalent groups derived from a saturated heterocyclic ring such as a saturated piperidine ring, piperazine ring, morpholine ring, pyrrolidine ring, indoline ring, chroman ring and the like can also be mentioned. When each of the above groups may have a substituent, examples of the substituent include a halogen atom, a hydroxyl group, a cyano group, a nitro group, an amino group, a carboxyl group, an alkylamino group, an alkyl group, and a halogenated alkyl group. , Alkoxy group, aryl group, aryloxy group,
An aralkyl group, an aralkoxy group, an alkylthio group and the like can be mentioned.

Specific examples of the above amide carboxylic acid compounds include, for example, succinamic acid, 2,2,3,3-tetramethylsuccinamic acid, 1,2-cyclohexanedicarbamic acid, 2,2,3,3 -Tetraethylsuccinamic acid, 2,3-diisopropylidenesuccinamic acid, 2,3-dimethylidenesuccinamic acid, 2-isopropylidene 3- [α- (phenyl) ethylidene] succinamic acid, 2- [ α- (2,4
Monocarboxylic acid amide compounds such as dimethyl-3-furyl) ethylidene] -3-isopropylidene succinamic acid and 2- [α- (3-thienyl) ethylidene] -3-adamantylidene succinamic acid are preferably used. Can be

As the halogen-containing compound as the other raw material in the present invention, known compounds are employed without any limitation. For example,
A halogen-containing compound represented by the following general formula is suitably used in the present invention.

Specific examples of the halogen-containing compound suitably used in the present invention are as follows, for example.

CH ₃ I, CH ₃ CH ₂ I, CH ₃ CH ₂ Br, CH ₃ CH ₂ CH ₂ Cl, And the like.

The reaction ratio of the above-mentioned halogen-containing compound is preferably selected from the range of 1.0 to 20 mol per 1 mol of the amide carboxylic acid compound, and the range of 2 to 10 mol is considered in view of the yield and cost of the product. It is suitable.

In the present invention, the reaction between the amide carboxylic acid compound and the halogen-containing compound is performed in a polar aprotic solvent. As the polar aprotic solvent, N-methylpyrrolidone, dimethylformamide, toluene, tetrahydrofuran and the like are used.

The greatest feature of the present invention resides in that the reaction between the amide carboxylic acid compound and the halogen-containing compound is performed in the presence of an alkali metal compound and an alkaline earth metal compound. As the alkali metal and alkaline earth metal, Li, N
a, K, Rb, Cs, Be, Mg, Ca, Sr, and Ba. These compounds include oxides, hydroxides, halides, carbonates,
Known compounds such as bicarbonate, sulfate and nitrate can be used without any limitation. In the present invention, in particular, K ₂ CO ₃ , Na ₂ C
O ₃ , NaHCO ₃ , MgO, CaO, BaCO _{3 and the} like can be suitably used, and particularly, oxides, carbonates, and hydrogen carbonates are preferably used. The amount of the alkali metal compound or alkaline earth metal compound used here is generally selected from the range of 1.0 to 20 mol per 1 mol of the above-mentioned amide carboxylic acid compound.

The reaction between the amide carboxylic acid compound and the halogen-containing compound is generally performed in the following procedure, but the order of addition is not limited. First, the amide carboxylic acid compound is dissolved in a polar aprotic solvent, and then a halogen-containing compound, an alkali metal compound or an alkaline earth metal compound is added to carry out the reaction. The reaction temperature is preferably selected from the range of -20 to 80 ° C in order to increase the reaction rate.

According to the method of the present invention, an amide ester compound in which a carboxyl group of an amide carboxylic acid compound as a raw material is esterified is obtained.

(Effects) According to the present invention, an amide carboxylic acid compound and a halogen-containing compound are reacted in a polar aprotic solvent in the presence of an alkali metal compound and an alkaline earth metal compound to obtain high yield and high purity. An amide ester compound can be obtained.

Further, among the amide ester compounds obtained by the method of the present invention, there are compounds having photochromic properties, and thus the method of the present invention can be used as a method for producing a photochromic compound.

(Examples) Hereinafter, typical examples will be shown to specifically explain the present invention, but the present invention is not limited to these examples.

Example 1 In a container equipped with a stirrer and a thermometer, 2,2,3,3-
Tetramethylsuccinamic acid After supplying 0.1 mol and 150 ml of dimethyl sulfoxide,
0.6 mol of methyl iodide, 0.8 mol of calcium oxide and 0.25 mol of calcium sulfate were added and stirred. Next, the reaction was performed overnight while controlling the temperature in the container to 25 ° C. After the completion of the reaction, the reaction solution was filtered using No. 5C (made by Toyo Roshi Kaisha) filter paper, and the filtrate was poured into a mixed solvent of chloroform and water and stirred vigorously. After stirring for about 5 minutes, the organic layer was separated by standing still. Thereafter, the organic layer was separated by washing with a 10% solution of sodium thiosulfate, and the organic layer was dehydrated with magnesium sulfate and filtered. Then, chloroform was expelled by an evaporator and dried by a vacuum drier to obtain 16.8 g (yield 90%) of a white compound represented by the following formula.

The product was analyzed by liquid chromatography to be 90% pure.

Comparative Example 1 0.1 mol of 2,2,3,3-tetramethylsuccinamic acid and 0.3 mol of methanol were placed in a vessel equipped with a stirrer and a thermometer.
Sulfuric acid is added to a mixture of mol and dichloroethane (30 ml).
Refluxed for 15 hours. After completion of the reflux, the mixture was allowed to cool, diluted with water, and the organic layer was separated.

This was washed with an aqueous solution of sodium hydrogen carbonate, dehydrated with magnesium sulfate, filtered, and the solvent was driven off by an evaporator.
A white compound represented by the following formula (yield 18.8%) was obtained.

The product was analyzed by liquid chromatography to be 90% pure.

Comparative Example 2 In the same container as in Comparative Example 1, 0.1 mol of 2,2,3,3-tetramethylsuccinamic acid, 0.11 mol of potassium carbonate, 0.11 mol of dimethyl sulfuric acid, and 100 ml of anhydrous acetone were added.
Refluxed for 5 hours. After completion of the reflux, the mixture was allowed to cool, and then filtered using No. 5C (made by Toyo Roshi Kaisha) filter paper. The filtrate was poured into a mixed solvent of chloroform and water and stirred vigorously. After stirring for about 5 minutes, the organic layer was separated by standing, dehydrated with magnesium sulfate, filtered, and the solvent was expelled with an evaporator, followed by drying with a vacuum dryer to obtain 7.0 g.
A white compound of the following formula (yield 37%) was obtained.

The product was analyzed by liquid chromatography and found to be 50% pure.

Comparative Example 3 0.1 mol of 2,2,3,3-tetramethylsuccinamic acid and 0.12 mol of triethyloxonium fluoroborate were dissolved in 200 ml of dichloromethane in the same container as in Comparative Example 1, and diisopropylethylamine 0.11 was added to the solution. Mole was added and left at room temperature for 24 hours. The solution was washed sequentially with a 1M aqueous hydrochloric acid solution, a 1M aqueous potassium hydrogen carbonate solution and a saturated aqueous sodium chloride solution, and then dried. Thereafter, the solvent was expelled using an evaporator, and then dried with a vacuum drier to obtain 4.5 g (yield: 22.4%) of a white compound represented by the following formula.

The product was analyzed by liquid chromatography and found to be 75% pure.

Examples 2 to 7 The same procedures as in Example 1 were carried out except that the amount of methyl iodide was changed as shown in Table 1.

 The results are shown in Table 1.

Examples 8 to 10 In Example 1, a halogen-containing compound and an alkali metal,
The procedure was carried out in the same manner as in Example 1 except that the alkaline earth metals or these compounds were changed as shown in Table 2.

 The results are shown in Table 2.

Examples 11 to 28 Various amide ester compounds were synthesized from the amide carboxylic acid compounds and the halogen-containing compounds shown in Table 3 in the same manner as in Example 1.

 The results are shown in Table 3.

Claims (1)

(57) [Claims] (1) A method for producing an amide ester compound, comprising reacting an amide carboxylic acid compound having a group represented by formula (I) with a halogen-containing compound in a polar aprotic solvent in the presence of an alkali metal compound or an alkaline earth metal compound.