JP3218755B2 - Glycerin ether ester - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel derivative of glycerin, glycerin ether ester, and more particularly to glycerin α-monopolyalkylene glycol ether ester.

[0002]

2. Description of the Related Art As derivatives in which a polyalkylene glycol and a fatty acid are bonded to glycerin, fatty acid esters of glycerin polyalkylene glycol ether and polyalkylene glycol ethers of glycerin monofatty acid ester are known, and are used as surfactants. ing.

[0003]

THE INVENTION Problems to be Solved] These compounds, while at α hydroxyl group and β hydroxyl group of glycerol Ru Ha occur easily the addition reaction, the oxyalkylene groups in many When all of the hydroxyl groups of the number of added moles of alkylene oxide When adding and reacting a fatty acid with glycerin, all the hydroxyl groups are similarly esterified, and in any case, an oxyalkylene group or an aliphatic acyl group is selectively introduced into a specific hydroxyl group of glycerin. Was difficult.

An object of the present invention is to provide a glycerin α-monopolyalkylene glycol ether ester in which an oxyalkylene group is bonded to only one α-position of glycerin.

[0005]

The present invention relates to a glycerin ether ester represented by the formula (1).

[0006]

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(Wherein R ¹ is a hydrocarbon group having 1 to 24 carbon atoms ,
R ² and R ³ are a hydrogen atom or an aliphatic acyl group having 2 to 22 carbon atoms, at least one of R ² and R ³ is an aliphatic acyl group, AO is an oxyalkylene group having 2 to 4 carbon atoms, n Is 5 to 1000. ) ¹ to 1 carbon atoms represented by R ¹
24 Hydrocarbon groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, hexyl, heptyl, 2-ethylhexyl, octyl, nonyl Group, decyl group, undecyl group, dodecyl group, tridecyl group, tetradecyl group, hexadecyl group, isocetyl group,
Octadecyl group, isostearyl group, oleyl group, octyldodecyl group, docosyl group, decyltetradecyl group,
Benzyl group, cresyl group, butylphenyl group, dibutylphenyl group, octylphenyl group, nonylphenyl group,
There are a dodecylphenyl group, a dioctylphenyl group, a dinonylphenyl group, a styrenated phenyl group, and the like, and a linear, branched, saturated or unsaturated aliphatic hydrocarbon group or aromatic hydrocarbon group.

The acyl groups represented by R ² and R ³ include acetic acid, propionic acid, butyric acid, isobutyric acid, caproic acid, caprylic acid, 2-ethylhexanoic acid, pelargonic acid, capric acid, undecylenic acid, lauric acid, Myristic acid, palmitic acid, margaric acid, stearic acid,
There are acyl groups derived from fatty acids such as arachiic acid, behenic acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, erucic acid, isopalmitic acid and isostearic acid.

Examples of the oxyalkylene group having 2 to 4 carbon atoms represented by AO include an oxyethylene group, an oxypropylene group, an oxybutylene group, an oxytetramethylene group, and the like. Good, 2
When more than one species are added, their addition state may be random or block. Typical production methods of the compound of the present invention include, for example, the following methods.

An alcohol or phenol is subjected to an addition reaction with an alkylene oxide having 2 to 4 carbon atoms, and the obtained polyoxyalkylene ether is reacted with epihalohydrin under an acidic catalyst to obtain an α-monohalohydrin derivative of glycerin. Next, an alkali is acted on this to form an epoxy compound by dehalogenating alkali, and further, the epoxy group is opened with an acid catalyst to obtain glycerin α-monopolyalkylene glycol ether.
It is a method of esterification with a fatty acid anhydride, a fatty acid chloride or the like, and is represented by the following reaction formula.

[0011]

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An alcohol or phenol is subjected to an addition reaction with an alkylene oxide having 2 to 4 carbon atoms, and the terminal of the obtained polyoxyalkylene ether is halogenated with a halogenating agent such as thionyl bromide. , 3-dioxolane in the presence of an alkali, followed by hydrolysis to obtain glycerin α-monopolyalkylene glycol ether, followed by esterification with a fatty acid, a fatty acid anhydride, a fatty acid chloride or the like. It is represented by

[0013]

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After reacting a dihydroxy α-monohalohydrin such as glycerin with a carbonyl compound such as acetone to obtain a halide of 1,3-dioxolane,
Reacting with the resulting polyoxyalkylene ether in the presence of or with an alkali to give the 1,3-
After obtaining α-polyalkylene glycol ether of dioxolane, it is hydrolyzed to synthesize glycerin α-monopolyalkylene glycol ether, which is then esterified with fatty acid, fatty acid anhydride, fatty acid chloride, etc. by the following reaction formula. It is represented by

[0015]

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[0016]

The glycerin ether ester of the present invention is a fatty acid ester having a polyoxyalkylene group bonded only to one α-position of glycerin. The glycerin ether ester of the present invention can be used as a surfactant, and by using it as a component of a liposome, the stability of a compound having a medicinal effect in blood can be improved.

[0017]

Next, the present invention will be described by way of examples. In addition,
Pressure unit kg / cm ² indicates gauge pressure, and% indicates weight%. Example 1 132 g (1 mol) of isopropylidene glycerol and 2.0 g of potassium hydroxide were placed in a 5-liter autoclave, the atmosphere in the system was replaced with nitrogen gas, and the temperature was raised to 100 ° C.
2300 g of ethylene oxide at 0 ° C and 10 kg / cm ² or less
(52.2 mol) was added over 3 hours, and the reaction was continued for another hour. Next, the mixture was cooled to 50 ° C. while distilling off unreacted ethylene oxide through nitrogen gas, and then 62.5 g (1.56 mol) of sodium hydroxide was added. After replacing with nitrogen, the temperature was raised to 100 ° C. with stirring. Next, methyl chloride was blown from the bomb, and the temperature was maintained at 100 ° C. for 3 hours while adjusting the blow tube so that the inside of the vessel became 1 atm. Thereafter, the mixture was cooled to 60 ° C. while blowing nitrogen gas, and excess methyl chloride was distilled off. The pH of the reaction mixture was adjusted to 1.0 using a 10% aqueous hydrochloric acid solution, and the mixture was stirred at 60 ° C. for 1 hour. The pH of the reaction mixture is then adjusted with 50% sodium hydroxide.
The temperature was adjusted to 6.5, and the mixture was heated at 100 ° C. and 100 mmHg or less for 1 hour, and acetone produced was distilled off together with water. The salt thus obtained was filtered off to obtain 2073 g of a compound A represented by the formula (A).

[0018]

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The obtained Compound A had a hydroxyl value of 46.6 (calculated value: 45.9) and a freezing point of 51.1 ° C. Next, 241 g (0.1 mol) of compound A, 60.0 g (0.2 mol) of methyl oleate and 0.2 mol of sodium methylate were placed in a 500 ml eggplant-shaped flask.
Take 2g, put under nitrogen and reduce pressure at 20mmHg at 80 ℃ 3
After transesterification for 1 hour, 1 g of Kyoward 600 (trade name, manufactured by Kyowa Chemical Industry Co., Ltd.) was added as a silica-based adsorbent, and the mixture was mixed at 80 ° C. for 1 hour under a nitrogen atmosphere, followed by filtration. The compound (1) of the present invention represented by
1 g was obtained.

[0020]

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The resulting compound (1) has a hydroxyl value of 0.3.
(Calculated value 0), ester value was 38.7 (calculated value 38.1), and freezing point was 43.1 ° C. Example 2 241 g (0.1%) of compound (A) obtained in the same manner as in Example 1
Mol) and 26 g (0.1 mol) of methyl myristate to obtain 255 g of the compound (2) of the present invention represented by the formula (2).

[0022]

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The obtained compound (2) has a hydroxyl value of 21.0.
(Calculated value 21.4), ester value was 21.5 (calculated value 21.4), and freezing point was 48.2 ° C. Example 3 Hereinafter, a block adduct of ethylene oxide and propylene oxide was synthesized in the same manner as in Example 1, and methyl laurate was reacted therewith in the same manner as in Example 1 to obtain a compound of the present invention represented by the formula (3). Compound (3) was obtained.

[0024]

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The resulting compound (3) has a hydroxyl value of 0.2.
(Calculated value 0), ester value was 102 (calculated value 101), and freezing point was 8.2 ° C. Example 4 491 g (1.5 mol) of docosyl alcohol and sodium hydroxide
Take 6.2 g into a 5 liter autoclave, replace the system with nitrogen gas, and raise the temperature to 100 ° C.
Under conditions of cm ² or less, 1450 g (32.9 mol) of ethylene oxide was added over 3 hours, and then 1188 g (16.5 mol) of 1,2-butylene oxide was added over 1 hour, and the reaction was continued for 1 hour. Next, the reaction product was cooled to 80 ° C., neutralized with dilute hydrochloric acid, dehydrated under reduced pressure with an evaporator, and the salt generated by filtration was removed. The ethylene oxide-butylene oxide block of docosyl alcohol represented by the formula (C) was removed. 2,850 g of polymer C was obtained. The hydroxyl value of the obtained compound (C) was 29.0 (calculated value 27.1).

[0026] _{CH 3 (CH 2) 21 O} (CH 2 CH 2 O) 20 (C 4 H 8 O) 10 H (C) then compound C2500g (1.3 mol) of 5-liter autoclave of tin tetrachloride 3.5g After replacing the inside of the system with nitrogen gas, 125 g (1.4 mol) of epichlorohydrin was added over 1 hour at 50 to 70 ° C. and 3 kg / cm ² or less, and further added.
The reaction was continued for 30 minutes. Thereafter, 390 g of a 20% aqueous sodium hydroxide solution was added, and the mixture was stirred at 70 to 80 ° C. for 2 hours and allowed to stand for 30 minutes. Thereafter, the separated aqueous layer (lower layer) was removed and washed with 1 liter of water twice. After washing with water, transfer to a four-necked flask,
2 liters of a 2% aqueous sulfuric acid solution, stirred at 80 to 90 ° C. for 3 hours, and allowed to stand for 30 minutes. Then, the separated aqueous layer (lower layer) was removed.
After further washing twice with 1 liter of water each time, dehydration was performed under reduced pressure using an evaporator, followed by filtration to obtain 2510 g of a monoglyceryl ether D of an ethylene oxide-butylene oxide block polymer of docosyl alcohol represented by the formula (D). . The hydroxyl value of the obtained compound D was 56.0 (calculated value 56.1).
Met.

[0027]

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[0028] Next, the compound in 500ml four-necked flask D30
0 g (0.15 mol) and 10 g of pyridine were taken and esterified by adding 31.6 g (0.31 mol) of acetic anhydride dropwise at 90-100 ° C. under a nitrogen atmosphere. After the esterification reaction, under reduced pressure of 30 mmHg or less
Pyridine and acetic acid are distilled off at 80 ° C., and 1.0 g of Kyoward 300 (Kyowa Chemical Industry Co., Ltd.) is added as a silica-based adsorbent. ) Was obtained in an amount of 290 g of the compound (5) of the present invention.

[0029]

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The hydroxyl value 0.1 of the compound (5) (calc 0), ester value was 53.6 (calculated value 53.8).

[Brief description of the drawings]

FIG. 1 is an infrared absorption spectrum of the compound (2) of the present invention.

──────────────────────────────────────────────────続 き Continuation of front page (56) References JP-A-4-290810 (JP, A) US Patent 5,135,683 (US, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C08G 65 / 32-65/338 C07C 69/30 CA (STN)

Claims (2)

(57) [Claims] 1. A glycerin ether ester represented by the formula (1). Embedded image (Wherein R ¹ is a hydrocarbon group having 1 to 24 carbon atoms , R ² and R ³
Is a hydrogen atom or an aliphatic acyl group having 2 to 22 carbon atoms, at least one of R ² and R ³ is an aliphatic acyl group, AO is an oxyalkylene group having 2 to 4 carbon atoms, and n is 5
~ 1000. ) 2. In the formula (1), R ¹ has ¹ to 2 carbon atoms.
R ² and R ³ are a hydrogen atom or carbon number
2 to 18 aliphatic acyl groups, and among R ² and R ³ ,
Kutomo one aliphatic acyl group, carbon number 1 to a R ¹
22 hydrocarbon groups and R ² or R ³ having 2 to 18 carbon atoms
The carbon number of the aliphatic acyl group of each is different from each other.
A glycerin ether ester as described above.