JPH10279541A - 2-substituted glycolate compound and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new compound in which a hydrogen at 2-site carbon is substituted with a polar functional group excluding alkyl groups and useful for a raw material, etc., of a biodegradable polymer. SOLUTION: This compound, is expressed by formula I (R1 is H or a lower alkyl; X and Y are each an organic residue and X and Y may be bonded with each other) e.g. 2-(2-oxo-hexamethylene imino)-methyl glycolate. The compound of formula I is obtained by reacting an NH-group in a nitrogen-containing compound (e.g. N-methylacetamide) of formula II (X and Y are each an organic residue) with an aldehyde group of a glyoxylate compound (e.g. methyl glyoxylate) of formula III, preferably using a method to add the glyoxylate of formula III or its solution to the nitrogen-containing compound of formula II or its solution, preferably at -100 deg.C to 250 deg.C, more preferably at 0-70 deg.C.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel 2-substituted glycolic acid compound and a method for producing the same. The 2-substituted glycolic acid compound of the present invention is useful as a raw material of a biodegradable polymer.

[0002]

2. Description of the Related Art Conventionally, as a 2-substituted glycolic acid compound, a compound such as lactic acid or an ester thereof in which hydrogen on the 2-position carbon has been replaced by a hydrocarbon group such as an alkyl group has been known. These compounds are useful as a raw material of the biodegradable polymer, but have only a non-polar group such as a hydrocarbon group as a substituent, so that various functions can be imparted to the obtained biodegradable polymer. It was very difficult.

[0003] Further, a 2-substituted glycolic acid compound in which hydrogen on the carbon at the 2-position is substituted with a polar functional group other than an alkyl group, and an industrially useful production method of the compound have not been known.

[0004]

SUMMARY OF THE INVENTION The present invention provides a novel 2-
An object of the present invention is to provide a substituted glycolic acid compound and a method for producing the same.

[0005]

The present invention provides a compound represented by the following general formula (1):

[0006]

Embedded image

Wherein R 1 is hydrogen or a lower alkyl group, X and Y are each independently an organic residue, and X and Y may be bonded to each other. For compounds.

Another invention of the present invention provides a compound represented by the following general formula (7):

[0009]

Embedded image

(Wherein X and Y are each independently an organic residue) and an NH group of a nitrogen-containing compound represented by the general formula (8):

[0011]

Embedded image

(Wherein R 1 is hydrogen or a lower alkyl group). The present invention relates to a 2-substituted glycolic acid compound obtained by reacting with an aldehyde group of a glyoxylate compound represented by the formula:

Another invention of the present invention provides a compound represented by the following general formula (7):

[0014]

Embedded image

(Wherein X and Y are each independently an organic residue), and a general formula (8):

[0016]

Embedded image

(In the formula, R1 is a lower alkyl group.)
The method for producing a 2-substituted glycolic acid compound according to any one of claims 1 to 6, wherein the reaction is carried out with a glyoxylate compound represented by the formula:

[0018]

BEST MODE FOR CARRYING OUT THE INVENTION The 2-substituted glycolic acid compound according to the present invention is a 2-substituted glycolic acid compound represented by the general formula (1). Specifically, the following general formula (2)
And 2-substituted glycolic acid compounds represented by (6).

General formula (2):

[0020]

Embedded image

(Wherein, R1 is hydrogen or a lower alkyl group, R2 and R3 are each independently hydrogen or an organic residue, and R2 and R3 may be bonded to each other.) General formula (3):

[0022]

Embedded image

Wherein R1 is hydrogen or a lower alkyl group, m and n are 0 or a positive integer, and m + n
Is 2 to 5, and A is a direct bond or a heteroatom selected from the group consisting of nitrogen, oxygen, sulfur, silicon and phosphorus. General formula (4):

[0024]

Embedded image

Wherein R 1 is hydrogen or a lower alkyl group, R 4 and R 5 are each independently a lower alkyl group,
A cycloalkyl group, an alkenyl group or a phenyl group, which may be bonded to each other; General formula (5):

[0026]

Embedded image

(Wherein R1 is hydrogen or a lower alkyl group, R6 and R7 are each independently a direct bond or an alkyl group, a cycloalkyl group, an alkenyl group or a phenyl group, and A is a direct bond. Or a kind of hetero atom selected from the group consisting of nitrogen, oxygen, sulfur, silicon and phosphorus.) General formula (6):

[0028]

Embedded image

Wherein R1 is hydrogen or a lower alkyl group, R8 and R9 are each independently hydrogen or an organic residue, and R8 and R9 may be bonded to each other. Specific examples of the glycolic acid compound include, for example, (1) a compound having an acyclic amide group such as 2- (N-methylacetamido) -glycolic acid ester and 2- (N-methylformamide) -glycolic acid ester; ) Methyl 2- (2-oxo-azetidino) -glycolate, methyl 2- (2-oxo-pyrrolidino) -glycolate, methyl 2- (2-oxo-piperidino) -glycolate, 2- (2-oxo- Hexamethyleneimino) -methyl glycolate, 2- (2-oxo-morpholino) -methyl glycolate, 2- (2-oxo-piperazino) -g Methyl cholate, 2- (oxazolidonyl) - compound having a cyclic amide group or cyclic urethane group methyl glycolate and the like; (3) 2- (acrylamido) - methyl glycolate,
2- (N-methylacrylamide) -methyl glycolate, 2- (N-ethylacrylamide) -methyl glycolate, 2- (N-propylacrylamide) -methyl glycolate, 2- (N-isopropylacrylamide) -glycolic acid Methyl, 2- (N-cyclohexylacrylamide) -methyl glycolate, 2- (N-phenylacrylamide) -methyl glycolate, 2-
(Methacrylamide) -methyl glycolate, 2- (N
-Methyl methacrylamide) -methyl glycolate, 2
-(N-ethyl methacrylamide) -methyl glycolate, 2- (N-propyl methacrylamide) -methyl glycolate, 2- (N-isopropyl methacrylamide) -methyl glycolate, 2- (N-cyclohexyl methacrylamide) -Methyl glycolate, 2- (N-
Compounds having a (meth) acrylamide structure such as phenylmethacrylamide) -methyl glycolate; (4) N-methyl such as 2- (N-vinylformamide) -methyl glycolate and 2- (N-vinylacetamido) -methyl glycolate A compound having a vinylamide structure; (5) methyl 2- (N, N-dimethylamino) -glycolate, methyl 2- (N, N-diethylamino) -glycolate, 2- (N, N-dipropylamino) -Methyl glycolate, 2- (N, N-diisopropylamino)
-Methyl glycolate, 2- (N, N-dibutylamino) -methyl glycolate, 2- (N, N-diphenylamino) -methyl glycolate, 2- (N-methyl-N
-Ethylamino) -methyl glycolate, 2- (N-methyl-N-propylamino) -methyl glycolate, 2
Compounds having an amino group, such as-(N-methyl-N-butylamino) -methyl glycolate and methyl 2- (N-methyl-N-phenylamino) -glycolate; (6) methyl 2-aziridino-glycolate Methyl 2-azetidino-glycolate, methyl 2-pyrrolidino-glycolate, methyl 2-piperidino-glycolate,
2-hexamethyleneimino-methyl glycolate, 2-
Compounds having an imino group such as methyl morpholino-glycolate, methyl 2-piperazino-glycolate, methyl 2-imidazolino-glycolate, and methyl 2-carbozolino-glycolate; (7) methyl 2-diacetamide-methyl glycolate; −
Compounds having an imide group, such as succinimide-methyl glycolate, 2-maleimide-methyl glycolate, and 2-phthalimido-methyl glycolate; and the like.

Further, the 2-substituted glycolic acid compound according to the present invention is a compound of the nitrogen-containing compound represented by the general formula (7).
2 obtained by reacting an H group with an aldehyde group of the glyoxylate compound represented by the general formula (8)
-A substituted glycolic acid compound.

Specific examples of the nitrogen-containing compound represented by the general formula (7) include a nitrogen-containing compound represented by any of the following general formulas (9) to (15).

Formula (9):

[0033]

Embedded image

(Wherein R2 and R3 are each independently hydrogen or an organic residue, and may be bonded to each other). N-substituted amide represented by the following general formula (10):

[0035]

Embedded image

Wherein m and n are 0 or a positive integer, and m + n is 2 to 5, and A is directly bonded or selected from the group consisting of nitrogen, oxygen, sulfur, silicon and phosphorus. A lactam or cyclic urethane represented by the following general formula (11):

[0037]

Embedded image

(Wherein R ₁₀ is an organic residue and R ₁₁ is hydrogen or a methyl group). N-substituted (meth) acrylamide represented by the general formula (12):

[0039]

Embedded image

(Wherein R ₁₂ is hydrogen or an organic residue) N-vinylamide represented by the general formula (13):

[0041]

Embedded image

(Wherein R4 and R5 are each independently an organic residue.) A secondary amine represented by the general formula (14):

[0043]

Embedded image

(Wherein, R6 and R7 are each independently a direct bond or an alkyl, cycloalkyl, alkenyl or phenyl group;
Is a direct bond or one heteroatom selected from the group consisting of nitrogen, oxygen, sulfur, silicon and phosphorus. The imine represented by the general formula (15):

[0045]

Embedded image

(Wherein R8 and R9 are each independently
It is hydrogen, a lower alkyl group, a cycloalkyl group, an alkenyl group or a phenyl group, and R8 and R9 may be bonded to each other. Examples of the nitrogen-containing compound represented by the general formula (7) include N-substituted amide compounds such as N-methylacetamide and N-methylformamide; 2-oxo-azetidine; Lactam or cyclic urethane compounds such as pyrrolidone, 2-piperidone, caprolactam, morpholinone, piperazinone, oxazolidone; (meth) acrylamide N-methyl (meth) acrylamide, N-ethyl (meth) acrylamide, N-propyl (meth) acrylamide, N -Isopropyl (meth) acrylamide,
N-substituted (meth) acrylamide compounds such as N-cyclohexyl (meth) acrylamide and N-phenyl (meth) acrylamide; N-vinylamide compounds such as N-vinylformamide and N-vinylacetamide; N, N-
Dimethylamine, N, N-diethylamine, N, N-dipropylamine, N, N-diisopropylamine, N, N-diisopropylamine
N-dibutylamine, N, N-diphenylamine, N-
N, N-substituted amine compounds such as methyl-N-ethylamine, N-methyl-N-propylamine, N-methyl-N-butylamine, N-methylaniline; and ethyleneimine, azetidine, pyrrolidine, piperidine, hexamethyleneimine, etc. Imine compounds; morpholine, piperazine, imidazoline, carbazole; diamide compounds such as diacetamide; imide compounds such as succinimide, maleimide and phthalimide.

Specific examples of the glyoxylate represented by the general formula (8) include methyl glyoxylate, ethyl glyoxylate, propyl glyoxylate, isopropyl glyoxylate, butyl glyoxylate, 2-ethylhexyl glyoxylate, and glyoxyl. Esters of alkyl alcohol, cycloalkyl alcohol or aromatic alcohol of glyoxylic acid such as octyl acid, cyclohexyl glyoxylate, phenyl glyoxylate and the like can be mentioned.

The method of reacting the nitrogen-containing compound represented by the general formula (7) with the glyoxylate compound represented by the general formula (8) is not particularly limited, but is represented by the general formula (7). The method of adding the glyoxylic acid ester represented by the general formula (8) or the solution thereof to the nitrogen-containing compound or the solution thereof includes the 2-substituted glycolic acid compound formed by the reaction and the general formula (8).
Is preferable in that a side reaction with a glyoxylic acid ester represented by formula (1) is suppressed, and the desired 2-substituted glycolic acid compound can be obtained with high selectivity.

In synthesizing the 2-substituted glycolic acid compound of the present invention, a solvent may be used if necessary. The solvent that can be used is not particularly limited as long as it does not inhibit the reaction between the aldehyde of glyoxylate and NH, and specific examples thereof include aliphatic hydrocarbons such as hexane and octane; Alicyclic saturated hydrocarbons such as cyclohexane; aromatic hydrocarbons such as benzene, toluene and xylene; ketones such as acetone and methyl ethyl ketone; esters such as methyl acetate, ethyl acetate and butyl acetate; Halogenated hydrocarbons such as carbon chloride; ethers such as diethyl ether, dioxane and dioxolane; amides such as dimethylformamide; sulfonic acid esters such as dimethyl sulfoxide; methanol;
Alcohols such as ethanol and 2-propanol and water can be mentioned, and one or more of these can be used.

When reacting the nitrogen-containing compound represented by the general formula (7) with the glyoxylate compound represented by the general formula (8), a catalyst is not particularly required. For the purpose of suppressing sodium hydroxide, potassium hydroxide, calcium hydroxide,
Basic catalysts such as sodium methylate, lithium methylate, sodium ethylate, hydrochloric acid, sulfuric acid, nitric acid,
An acid catalyst such as methanesulfonic acid and zeolite may be used.

The reaction temperature for reacting the nitrogen-containing compound represented by the general formula (7) with the glyoxylate compound represented by the general formula (8) is not particularly limited. It is preferable to react in a temperature range not lower than the melting point and not higher than the boiling point of the amide compound and the glyoxylate compound to be used, and from the viewpoint of easy control of the reaction temperature, a temperature range of -100 ° C to 250 ° C is preferable, and The temperature range is more preferably 0 to 70 ° C. from the viewpoint that the 2-substituted glycolic acid compound of the present invention can be obtained efficiently and with high selectivity.

[0052]

EXAMPLES The present invention will now be described specifically with reference to examples, but the present invention is not limited to these examples.

Example 1 169.74 g of ε-caprolactam and 150 ml of chloroform were charged into a 500 ml four-necked flask equipped with a stirrer, a cooler, a thermometer, a nitrogen inlet tube and a dropping funnel, and stirred at room temperature. -Caprolactam was completely dissolved in chloroform.

Next, while maintaining the temperature in the flask at 5 ° C. or lower in an ice water bath, methyl glyoxylate 13
2.09 g was dropped from the dropping funnel over about 1 hour, and then aged at 5 ° C. for 2 hours.

The resulting reaction solution was transferred to a 500 ml eggplant-shaped flask, and about 120 ml of chloroform was distilled off using a rotary evaporator. After that, the content was left at room temperature for 48 hours to precipitate crystals.

The precipitated crystals were filtered off with suction using a Buchner funnel and separated by filtration. The crystals on the funnel were washed several times with diethyl ether and dried at room temperature under reduced pressure to obtain about 210 g of the product of Example (1) ( (Yield: 70%).

The product (1) was methyl 2- (2-oxo-hexamethyleneimino) -glycolate from the result of ¹ H-nuclear magnetic resonance spectrum, infrared absorption spectrum and elemental analysis of the product (1). It was confirmed. ¹ H
FIG. 1 shows an NMR chart, FIG. 2 shows an infrared absorption spectrum, and Table 1 shows the results of elemental analysis.

[0058]

[Table 1]

Example 2 85.11 g of 2-pyrrolidone and chloroform 1 were placed in a 300 ml four-necked flask equipped with a stirrer, a cooler, a thermometer, a nitrogen inlet tube and a dropping funnel.
00 ml was charged.

Next, while maintaining the temperature in the flask at 5 ° C. or lower in an ice water bath, methyl glyoxylate 13
2.09 g was dropped from the dropping funnel over about 1 hour, and then aged at 5 ° C. for 2 hours.

The obtained reaction solution was transferred to a 500 ml eggplant-shaped flask, and about 120 ml of chloroform was distilled off using a rotary evaporator. Then, the contents were added to 2 l of diethyl ether at a stretch to precipitate crystals.

The precipitated crystals were filtered off with a Buchner funnel by suction filtration, and the crystals on the funnel were washed several times with diethyl ether and dried at room temperature under reduced pressure to give about 105 g of the product of Example (2) ( Yield: 61%).

From the results of ¹ H-nuclear magnetic resonance spectrum, infrared absorption spectrum and elemental analysis of the product (2), it was confirmed that the product (2) was methyl 2- (2-oxo-pyrrolidino) -glycolate. confirmed. FIG. 3 shows a chart of ¹ H-NMR, FIG. 4 shows an infrared absorption spectrum, and Table 2 shows a result of elemental analysis.

[0064]

[Table 2]

Example 3 In a 100 ml four-necked flask equipped with a stirrer, a condenser, a thermometer, a nitrogen inlet tube and a dropping funnel, 14.22 g of pyrrolidine and 30 m of chloroform were placed.
l was charged.

Next, while maintaining the temperature in the flask at 5 ° C. or lower in an ice water bath, methyl glyoxylate 1
7.61 g was dropped from the dropping funnel over about 15 minutes, and then aged at 5 ° C. for 2 hours.

The obtained reaction solution was transferred to a 100 ml eggplant-shaped flask, and about 20 ml of chloroform was distilled off using a rotary evaporator. Then, the content was added at a stretch to 2 liters of diethyl ether to precipitate crystals.

The precipitated crystals were filtered off with suction using a Buchner funnel and separated by filtration. The crystals on the funnel were washed several times with diethyl ether and dried at room temperature under reduced pressure to obtain about 13 g of the product of Example (3) ( Yield: 40%).

From the ¹ H-nuclear magnetic resonance spectrum and the infrared absorption spectrum of the product (3), the product (3)
It was confirmed to be methyl pyrrolidino-glycolate. ^{The 1} H-NMR chart is shown in FIG. 5 and the infrared absorption spectrum is shown in FIG.

Example 4 A 100 ml four-necked flask equipped with a stirrer, a condenser, a thermometer, a nitrogen inlet tube and a dropping funnel was charged with 7.45 g of isopropylacrylamide and 20 ml of chloroform.

Next, while maintaining the temperature in the flask at 5 ° C. or lower in an ice water bath, methyl glyoxylate was added under stirring.
80 g was dropped from the dropping funnel over about 10 minutes, and then aged at 5 ° C. for 2 hours.

The obtained reaction solution was transferred to a 100 ml eggplant-shaped flask, and chloroform was almost completely distilled off using a rotary evaporator, whereby about 12 g (crude yield: 90%) of Example product (4) was obtained. Was.

FIG. 7 shows the ¹ H-nuclear magnetic resonance spectrum of the product (4).

Example 5 In a 100 ml four-necked flask equipped with a stirrer, a cooler, a thermometer, a nitrogen inlet tube and a dropping funnel, 19.82 g of succinimide and chloroform 3 were added.
0 ml was charged.

Next, while maintaining the temperature in the flask at 65 ° C. with a water bath, 17.6 g of methyl glyoxylate was stirred.
2 g was dropped from the dropping funnel over about 20 minutes, and then aged at 60 ° C. for 2 hours.

The obtained reaction solution was transferred to a 100 ml eggplant-shaped flask, and about 20 ml of chloroform was distilled off using a rotary evaporator. Then, the content was left at room temperature to precipitate white needle-like crystals.

The precipitated crystals were filtered off with a Buchner funnel by suction filtration, and the crystals on the funnel were washed several times with chloroform and dried at room temperature under reduced pressure to obtain about 18 g of the product of Example (5). Was.

From the ¹ H-nuclear magnetic resonance spectrum and the infrared absorption spectrum of the product (5), the product (5)
It was confirmed that the mixture was a mixture of (succinimide) -methyl glycolate and unreacted succinimide. ¹ H-
FIG. 8 shows an NMR chart, and FIG. 9 shows an infrared absorption spectrum.

[0079]

According to the present invention, a novel 2-substituted glycolic acid compound useful as a raw material for a biodegradable polymer can be provided.

Further, according to the production method of the present invention, the 2-substituted glycolic acid compound can be produced efficiently.

[Brief description of the drawings]

FIG. 1 shows a ¹ H-nuclear magnetic resonance spectrum of methyl 2- (2-oxohexamethyleneimino) -glycolate obtained in Example 1.

FIG. 2 shows an infrared absorption spectrum of methyl 2- (2-oxohexamethyleneimino) -glycolate obtained in Example 1.

FIG. 3 shows a ¹ H-nuclear magnetic resonance spectrum of methyl 2- (2-oxopyrrolidino) -glycolate obtained in Example 2.

FIG. 4 shows an infrared absorption spectrum of methyl 2- (2-oxopyrrolidino) -glycolate obtained in Example 2.

FIG. 5 shows the ¹ H-nuclear magnetic resonance spectrum of methyl 2-pyrrolidino-glycolate obtained in Example 3.

FIG. 6 shows an infrared absorption spectrum of methyl 2-pyrrolidino-glycolate obtained in Example 3.

FIG. 7 shows the ¹ H-nuclear magnetic resonance spectrum of the product (4) obtained in Example 4.

FIG. 8 shows the ¹ H-nuclear magnetic resonance spectrum of the product (5) obtained in Example 5.

FIG. 9 shows an infrared absorption spectrum of a product (5) obtained in Example 5.

Claims (8)

[Claims] 1. General formula (1): (Wherein R1 is hydrogen or a lower alkyl group, X and Y
Are each independently an organic residue, and X and Y may be bonded to each other. A) 2-substituted glycolic acid compound represented by 2. General formula (2): (Wherein R1 is hydrogen or a lower alkyl group, R2 and R3 are each independently hydrogen or an organic residue,
And R3 may be bonded to each other. The 2-substituted glycolic acid compound according to claim 1, which is represented by the formula: 3. A compound of the general formula (3): (Wherein R1 is hydrogen or a lower alkyl group, m and n
Is 0 or a positive integer, m + n is 2 to 5, and A is a direct bond or a kind of heteroatom selected from the group consisting of nitrogen, oxygen, sulfur, silicon and phosphorus. The 2-substituted glycolic acid compound according to claim 1, which is represented by the formula: 4. A compound of the general formula (4): (Wherein R1 is hydrogen or a lower alkyl group, R4 and R5 are each independently a lower alkyl group, a cycloalkyl group, an alkenyl group or a phenyl group, and may be bonded to each other). The 2-substituted glycolic acid compound according to the above. 5. A compound of the general formula (5): (Wherein, R 1 is hydrogen or a lower alkyl group, R 6 and R 7 are each independently directly bonded, or an alkyl group, cycloalkyl group, alkenyl group or phenyl group, and A is directly bonded, Or a heteroatom selected from the group consisting of nitrogen, oxygen, sulfur, silicon and phosphorus.) 6. A compound of the general formula (6): Wherein R 1 is hydrogen or a lower alkyl group, R 8 and R 9 are each independently hydrogen or an organic residue,
And R9 may be bonded to each other. 2)
-Substituted glycolic acid compounds. 7. A compound of the general formula (7): (Wherein X and Y are each independently an organic residue) and the NH group of the nitrogen-containing compound represented by the general formula (8): (Wherein, R1 is hydrogen or a lower alkyl group.) A 2-substituted glycolic acid compound obtained by reacting with a aldehyde group of a glyoxylate compound represented by the formula: 8. A compound of the general formula (7): (Wherein X and Y are each independently an organic residue) and a nitrogen-containing compound represented by the general formula (8): (Wherein, R1 is a lower alkyl group.) 7. A method for producing a 2-substituted glycolic acid compound according to any one of claims 1 to 6, wherein the compound is reacted with a glyoxylate compound represented by the formula: Method.