JPH0621087B2 - Method for producing glyceryl ether - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing glyceryl ether.

[Conventional technology]

As the α-monoalkyl glyceryl ether, palmitic glyceryl ether, stearyl glyceryl ether, oleyl glyceryl ether and the like which are conventionally present in lipids of fish are known, and these are emulsifiers, especially W.
/ O-type emulsifier having excellent performance (Japanese Patent Application Laid-Open Nos. 49-87612, 49-92239 and 52-
12109), as well as pharmacological actions such as hematopoiesis-promoting effect in bone marrow, anti-inflammatory action, antitumor activity, etc. (Japanese Patent Publication Nos. 1010724 / 52-52).
18171). Furthermore, in recent years, it has been reported to be used as an antibacterial and antifungal agent (Japanese Patent Publication No. 54-2249).
issue).

The following methods are conventionally known as methods for producing these α-monoglyceryl ethers from corresponding alcohols.

(1) (In the formula, R ¹ is a hydrocarbon group, R ² and R ³ are lower alkyl groups, X is a halogen atom, and M is an alkali metal.) That is, alcohol is a halide and a hydroxyl group is protected by this. This is a method of reacting glycerol alkali metal alcoholate to lead to 4-alkoxymethyl-1,3-dioxolane, and then hydrolyzing this.

(2) (In the formula, R ¹ and X are the same as above.) That is, a method of reacting an alcohol with epihalohydrin to obtain a glycidyl ether, and hydrolyzing this.

(3) (In the formula, R ⁴ represents a hydrocarbon group, and R ¹ is the same as above.) That is, the glycidyl ether obtained by the above-mentioned known method (2) is reacted with a carboxylic acid to obtain an α-glycerol monoester compound. , Is a method of hydrolyzing this.

(Four) (In the formula, R ⁵ and R ⁶ represent a hydrocarbon group, and R ¹ is the same as the above.) That is, the method previously reported by the present inventors, in which a carbonyl compound is added to glycidyl ether to give 1,3
-A method of leading to a dioxolane compound and hydrolyzing the compound (JP-A-56-133281).

(Five) (In the formula, R ⁷ represents a hydrocarbon group and R ¹ is the same as above.) That is, the method previously reported by the present inventors, in which glycidyl ether is reacted with a carboxylic acid anhydride in the presence of a catalyst, It is a method of leading to a diester compound and hydrolyzing it.

[Problems to be solved by the invention]

However, these known methods have some drawbacks.

In the method (1), (i) a glycerol compound 4-hydroxymethyl-1,3-protected with a hydroxyl group as a raw material is used.
Dioxolane) can be synthesized from glycerin and a carbonyl compound in the presence of an acid catalyst, but the reaction time is long and a large amount of dehydrating agent is required because it is a dehydration reaction.
(B) Alkyl halide and 4-hydroxymethyl-1,
In the condensation reaction of 3-dioxolane with an alkali metal alcoholate, since a strong base exists in the reaction system, a part of the alkyl halide produces a terminal olefin by dehydrohalogenation reaction, and the desired 4-alkoxymethyl-1, Three
-Reduces the yield of dioxolane.

In the method (2), since the reaction system is a heterogeneous system of water and oil, it is difficult to carry out a homogeneous reaction, and a large amount of a by-product of glycidyl ether is added in addition to the desired glyceryl ether. Therefore, the yield of glyceryl ether decreases and the quality becomes poor. Therefore, an operation such as molecular distillation is required to obtain high-purity glyceryl ether, which is an obstacle to implementation on an industrial scale.

In the method (3), since the monoester compound of α-alkylglycerol produced by the addition of an acid to glycidyl ether has a free hydroxyl group having active hydrogen, 1 mol or more of this free hydroxyl group is further added. There is a drawback that glycidyl ether is added to form a high molecular weight compound as a by-product. Therefore, the glyceryl ether obtained by this method has extremely low purity.

In the method (4), the ketone or aldehyde produced by the hydrolysis of the 1,3-dioxolane compound causes aldol condensation with the acid catalyst present in the reaction system, which causes coloration or odor.

In the method of (5), since the diester is hydrolyzed under a strong acid group condition, neutralization at the post-treatment stage, a large amount of water is required for washing, so that industrial problems are to be solved. Is left.

As described above, the conventional method uses glyceryl ether with high purity,
None of these production methods are yet sufficient for high yield and easy production.

[Means for solving problems]

The inventors of the present invention conducted various studies to overcome the drawbacks of the conventional method and produce α-monoglyceryl ether in high yield, high purity and simply, and found that the epoxide ring-opening reaction of glycidyl ether was carried out. It was found that these problems can be solved by carrying out using benzyl alcohol and a base, and completed the present invention.

That is, the present invention has the general formula (II) (In the formula, R represents a linear or branched alkyl group or aryl group having 1 to 26 carbon atoms) is reacted with benzyl alcohol in the presence of a base, and then the obtained product is present in the presence of a metal catalyst. General formula characterized by hydrocracking under
(I) (Wherein R is the same as above).

Among R of the glyceryl ether represented by the general formula (I) obtained in the present invention, as the linear or branched alkyl group having 1 to 26 carbon atoms, methyl, ethyl, n-propyl, n-butyl, n- Pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-
Undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-
Heptadecyl, n-octadecyl, n-nonadecyl, n
-Eicosyl, n-heneicosyl, n-docosyl, n
-Tricosyl, n-tetracosyl, n-pentacosyl,
Linear saturated primary alkyl group such as n-hexacosyl; 2-
Ethylhexyl, 2-butyldecyl, 2-ethyldodecyl, 2-butyldodecyl, 2-ethyltetradecyl, 2
-Hexyldecyl, 2-butyltetradecyl, 2-ethylhexadecyl, 2-hexyldecyl, 2-butylhexadecyl, 2-ethyloctadecyl, 2-hexyltetradecyl, 2-octyldodecyl, 2-butyloctadecyl, 2- Ethyl eicosyl, 2-hexyl hexadecyl, 2-octyl tetradecyl, 2-butyl eicosyl, 2-ethyl docosyl, 2-hexyl octadecyl,
2-octylhexadecyl, 2-butyldocosyl, 2-
Ethyl tetracosyl, 2-hexyl eicosyl, 2-octyl octadecyl, 2-heptyl undecyl, 2-
(1,3,3-Trimethylbutyl) octyl, 2-decyltetradecyl, 2-dodecylhexadecyl, 2-tetradecyloctadecyl, 5,7,7-trimethyl-2-
(1,3,3-trimethylbutyl) octyl and the following formula (In the formula, m represents an integer of 4 to 10, n represents an integer of 5 to 11, m + n represents 11 to 17, and m = 7, n = 8.
A branched primary primary saturated alkyl such as methyl-branched isostearyl represented by the formula: 2-propyl, sec-butyl, sec-pentyl, sec-hexyl, sec
Secondary saturated alkyl groups such as -heptyl, sec-octyl, sec-nonyl, sec-decyl, sec-undecyl, sec-dodecyl are mentioned. As the aryl group, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-
Dimethylphenyl, 3,4-dimethylphenyl, 3,5
-Dimethylphenyl and the like.

The present invention can be shown as a reaction formula as follows.

(In the formula, R is the same as above.) In the above reaction formula, the reaction for obtaining the benzyl ether (III) from the glycidyl ether (II) is an alcohol addition reaction to the epoxide derived from the terminal olefin. When an acid catalyst is used, the epoxide is protonated, and the alcohol attacks the carbonium ion generated thereby, so that a side reaction is likely to occur. However, in the present invention, since the reaction is performed in the presence of a base, the reaction proceeds at SN2, and the produced secondary alcohol has a large steric hindrance and does not cause a side reaction.

Examples of the base used include alkali metals (Li, Na,
K), alkali metal hydrides (LiH, NaH, K
H, etc.), alkali metal hydroxides (LiOH, NaO
H, KOH, etc.), alkali metal alcoholates (NaO
Me, NaOEt, KOt-Bu, etc., or tertiary amines (triethylamine, tributylamine, tetramethylethylenediamine, tetramethyl-1,3-diaminopropane, tetramethyl-1,6-diaminohexane, triethylenediamine, pyridine, Dimethylaniline, quinoline, etc.) and the like.

In this reaction, generally 1 to 20 mol, preferably 2 mol of pendyl alcohol is used per 1 mol of glycidyl ether (II).
10 to 10 mol, 0.001 to 0.5 mol of base, preferably 0.01 to 0.25 mol added, 20 to 150
The reaction proceeds under a temperature condition of 40 ° C, preferably 40 to 100 ° C.

Benzyl ether derivative (III) thus obtained
Can be easily purified by means such as distillation after distilling off excess benzyl alcohol, and the yield is always 85% or more, and in most cases quantitative.

Glyceryl ether from benzyl ether derivative (III)
The reaction for obtaining (I) is carried out by adding hydrogen in the absence of a solvent or in the presence of a metal catalyst.

As the metal catalyst, palladium-carbon, palladium black,
Raney-Nitzkel, rhodium-carbon, ruthenium-carbon,
Rhenium-carbon and the like can be used, but 5% palladium-carbon, 10% palladium-carbon, and palladium black are preferable. Examples of the solvent used in this reaction include all solvents that dissolve the benzyl ether derivative (III), but alcohol-based solvents such as methanol, ethanol, and isopropanol are preferable.

This reaction gives a benzyl ether derivative (III) in an amount of 0.0001 to 10% by weight, preferably 0.0001% by weight.
1-5 wt% metal catalyst is added, hydrogen pressure is 1-150 atm, preferably 50-120 atm, reaction temperature is 20-20.
Glyceryl ether (I) is quantitatively obtained by reacting at 0 ° C., preferably 80 to 120 ° C. for 2 to 24 hours, preferably 5 to 15 hours.

In this reaction system, the benzyl ether derivative (III)
0.01 to 1% by weight, preferably 0.1 to 0.7
The reaction is further facilitated by adding 5% by weight of mineral acid. Examples of the mineral acid to be added include hydrochloric acid, sulfuric acid, perchloric acid and the like, and hydrochloric acid is preferably used.

In most cases, the glyceryl ether (I) thus obtained is isolated as a pure product by simply removing the metal catalyst and then distilling off the solvent. When an acid is added, pure glyceryl ether (I) can be obtained by simple purification such as steaming or treatment with activated carbon. The separated metal catalyst can be reused.

In this reaction, the conventional debenzylation reaction requires 1) the use of a large amount of expensive metal catalyst, which inevitably leads to an increase in product price. 2) Generally, the reaction is carried out at a hydrogen pressure of 1 atm. Therefore, the debenzylation product needs to be isolated and purified although the reaction may be slow.
1) Use only a very small amount of metal catalyst, 2) Make sure that the reaction is completed in 2 to 24 hours, 3) Literally quantitative reaction, and isolation and purification of the debenzylated product is often unnecessary. If it is necessary, it is excellent in various points such as steaming, activated carbon treatment, and other simple means, and has advantages such as industrial implementation.

[Operation and effect of the invention]

As described above, according to the present invention, glyceryl ether (I) can be easily produced with high yield and high purity.

〔Example〕

 Next, the present invention will be described with reference to examples.

Example 1 (i) Tetradecyl glycidyl ether (II) (R = C ₁₄
Preparation of C ₂₉ ) 5 equipped with reflux condenser, thermometer, dropping funnel and stirrer
Tetradecyl alcohol 857.6 in a four-necked flask
g (4.0 mol), n-hexane 600 g, 50% tetrabutylammonium hydrogen sulfate aqueous solution 135.8 g
(0.2 mol), epichlorohydrin 740.0 g
(8.0 mol) was added in this order, the inside of the flask was kept at 20 to 30 ° C. in the cooling tank, and the mixture was stirred at a stirring speed of 400 rpm. 1100 g of 48% aqueous sodium hydroxide solution
(12.0 mol) was added dropwise over 2 hours while maintaining the reaction temperature at 25 to 30 ° C., and after completion of the addition, 25 to 3 was similarly added.
The mixture was stirred at 0 ° C for 3.5 hours. After completion of the reaction, the mixture was post-treated by a conventional method and distilled under reduced pressure to give tetradecyl glycidyl ether 7
39. g (yield 68.4%) was obtained.

Boiling point: 130-135 ° C./0.15 Torr IR (liquid film cm ⁻¹ ): 3050, 2925, 2860, 1460, 1107 NMR (CDCl ₃ , δ): 0.85 (3H, t, J = 5.4 Hz), 1.25 ( 24H, br
s), 2.4~3.9 (7H, m ) (ii) 1-O- tetradecyl -3-O-benzyl glycerol _{(III) (R = C 14} C 29) of a reflux condenser, a thermometer, inlet tube, dropping Benzyl alcohol
1.4 g (10.0 mol) is charged, 2.3 g (0.1 mol) of sodium is added while blowing nitrogen, and the mixture is stirred at room temperature until sodium is completely dissolved. Here (i)
Tetradecyl glycidyl ether 270.5 obtained in
g (1.0 mol) is added dropwise over 1 hour. After completion of dropping, the mixture is reacted at 90 ° C. for 4.5 hours, and disappearance of raw materials is confirmed by gas chromatography. After cooling, 1500 ml of ether was added, the ether layer was washed with water, separated and dried, the ether and benzyl alcohol were distilled off, and the residue was distilled under reduced pressure.
O-tetradecyl-3-O-benzylglycerin 35
9.3 g (yield 94.9%) was obtained.

Boiling point: 199 ° C / 0.06Torr-220 ° C / 0.08To
rr IR (liquid film, cm ^-1 ): 3440br, 3030, 2910, 2850, 1460sh, 1
450, 1100, 730, 696, 685 NMR (CDCl ₃ , δ): 0.87 (3H, t), 1.25 (24H, br)
s), 2.75 (1H, d, J = 4.0Hz), 3.3 to 3.6 (4H, m), 3.90 (1H, m), 4.48 (2)
H, s), 7.25 (5H, s) (iii) α-monotetradecyl glyceryl ether (I)
Production of (R = C ₁₄ C ₂₉ ) 50.0 g (0.1%) of 1-O-tetradecyl-3-O-pedylglycerin obtained in (ii) in the autoclave of 1.
32 mol), 100 g of methanol, 2.5 g of 5% palladium-carbon, and 0.25 g of concentrated hydrochloric acid are charged and sealed by applying a hydrogen pressure of 100 atm, and then heated and stirred at 100 ° C. for 10 hours. After cooling, 5% palladium carbon is filtered off and the solvent is distilled off. After the residue was steamed at 50%, 80 ml of a mixed solvent of methanol / n-hexane = 1: 1 and 3.6 g of activated carbon were added, and the mixture was stirred at room temperature for 1 hour. Activated carbon was filtered off and the solvent was distilled off to obtain 35.9 g (yield 94.2%) of colorless crystals of α-monotetradecyl glyceryl ether.

Elemental analysis As C ₁₇ H ₃₆ O ₃ (calculated value) C: 71.01 (70.78) H: 12.41 (12.
58) IR (liquid film, cm ⁻¹ ): 3385 br, 2935, 2860, 1480, 133
6, 1130, 1108, 1068, 940, 724,
690 NMR (CDCl ₂ , δ): 0.87 (3H, t), 1.23 (24H, br)
s), 2.75 (1H, br), 3.00 (1H, br), 3.3 to 3.9 (7H, m) IR and NMR were completely consistent with the standard.

Example 2 (i) 1-O- methyl-branched isostearyl -3-O-benzyl glycerol (III) (R = iso- C 18 H 37) of a reflux condenser, a thermometer, inlet tube, dropping funnel and stirrer Benzyl alcohol 54 in a two-neck flask equipped with a device
0.7 g (5.0 mol) is charged, 1.15 g (0.05 mol) of sodium is added while blowing nitrogen, and the mixture is stirred at room temperature until sodium is completely dissolved. 63.3 g (0.5 mol) of methyl-branched isostearyl glycidyl ether obtained according to Example 1 (i) was added thereto.
Add dropwise at 0 ° C. over 0.5 hours. After the dropping is completed, the reaction is carried out at 80 ° C. for 7.5 hours, and the disappearance of the raw materials is confirmed by gas chromatography. After cooling, the penzyl alcohol was distilled off, and the residue was distilled under reduced pressure to obtain 185.7 g of 1-O-methyl branched isostearyl-3-O-benzylglycerin (yield 85.4%).

Boiling point: 200 to 235 ° C./0.05 Toor IR (liquid film, cm ⁻¹ ): 3430 br, 3030, 2900, 2850, 1455 sh, 1448, 1360, 1100, 72
5, 695 sh, 683 NMR (CDCl ₃ , δ): 0.75 to 2.00 (35 H), 2.64 (1 H, d,
J = 4.0 Hz), 3.3 to 3.7 (6 H, m), 3.90
(1H, m), 4.50 (2H, s), 7.23 (5
H, s) (ii) Preparation of α-monomethyl branched isostearyl glyceryl ether (I) (R = iso-C ₁₈ H ₃₇ ). 1-O obtained in Example 2 (i) in the autoclave of 1.
-Methyl-branched isostearyl-3-O-benzylglycerin 100 g (0.23 mol), methanol 200 g,
Palladium black (0.25 g) was charged and sealed under a hydrogen pressure of 100 atm, and the mixture was heated and stirred at 100 ° C. for 10 hours. After cooling, palladium black was filtered off and the solvent was distilled off to obtain 79.3 g (yield 100%) of α-monomethyl branched isostearyl glyceryl ether as a colorless oily substance.

Elemental analysis As C ₂₁ H ₄₄ O ₃ (calculated value) C: 73.23 (73.20) H: 12.79 (12.
87) IR (liquid film, cm ⁻¹ ): 3400 br, 2925, 2860, 1470, 138
0, 1122, 1050 NMR (CDCl ₃ , δ): 0.75 to 1.7 (35H), 3.2 to 4.2 (9H, br)
m), IR and NMR were completely in agreement with the standard.

Example 3 (i) 1-O-hexyl-3-O-pentylglycerin
(III) Production of (R = C ₆ H ₁₃ ) Benzyl alcohol 1 in a 200 ml four-necked flask equipped with a reflux condenser, thermometer, introduction tube, dropping funnel and stirring device.
08.14 g (1.0 mol) was charged, 0.23 g (0.01 mol) of sodium was added while blowing nitrogen, and the mixture was stirred and dissolved at room temperature. 15.82 g (0.1 mol) of hexyl glycidyl ether is added dropwise thereto over 0.5 hour. After completion of dropping, the mixture is reacted at 60 ° C. for 8 hours, allowed to cool, neutralized, benzyl alcohol is distilled off, and the mixture is applied to a silica gel short column. It was dissolved in n-hexane / ethyl acetate = 5/1, and the solvent was distilled off to obtain 24.8 g of 1-O-hexyl-3-O-benzylglycerin (yield 93.1%).

IR (liquid film, cm ^-1 ): 3430 br, 3030, 2900, 2850, 1460 sh, 1450, 1100, 730, 695,
685 NMR (CDCl ₃ , δ): 0.87 (3H, t), 1.25 (8H, br m), 2.75 (1H, d, J = 4.0Hz), 3.3 to 3.6 (4H, m). ), 3.90 (1H, m), 4.50 (2
H, s), 7.27 (5H, s) (ii) α-monohexyl glyceryl ether (I) (R =
C ₆ H ₁₃₎ 1 obtained in Example 3 (i) to autoclave fabrication 100ml of
-O-hexyl-3-O-benzylglycerin 23.7
g (0.089 mol), 23.7 g of methanol and 0.06 g of palladium black were charged and sealed under a hydrogen pressure of 100 atm, and then heated and stirred at 100 ° C. for 5 hours. After cooling, palladium black was filtered off and the solvent was distilled off to obtain 15.69 g of α-monohexyl glyceryl ether as a colorless liquid (yield 10
0%).

Elemental analysis As C ₉ H ₂₀ O ₃ (calculated value) C: 61.45 (61.33) H: 11.33 (11.
44) IR (liquid film, cm ⁻¹ ): 3380 br, 2940, 2850, 1480, 134
0, 1125, 1110, 1070, 940, 725,
690 NMR (CDCl ₃ , δ): 0.87 (3H, t), 1.24 (8H, br m),
2.74 (1H, br), 3.00 (1H, br), 3.
3-3.9 (7H, m) IR and NMR were completely in agreement with the standard.

Claims (1)

[Claims] 1. General formula (II) (In the formula, R represents a linear or branched alkyl group or aryl group having 1 to 26 carbon atoms) is reacted with benzyl alcohol in the presence of a base, and then the obtained product is present in the presence of a metal catalyst. General formula characterized by hydrocracking under
(I) (In the formula, R is the same as the above).