JP3408337B2 - Method for producing glycerin derivative - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a glycerin derivative. More specifically, it relates to a method for producing a glycerin derivative, which is used as an excellent cosmetic oil having a less sticky feel, easily and inexpensively.

[0002]

2. Description of the Related Art Heretofore, esters such as triester of glycerin and diester of neopentyl glycol have been widely used as oil agents blended in cosmetics. However, esters have the drawback of having a strong oily feel, and are not always satisfactory as cosmetic oils, and inexpensive oils that can be manufactured easily with high performance are desired.

JP-A-52-54033 and JP-A-5-54033
2-54018 discloses glycerin triether as a cosmetic and an ointment base, respectively, and introduces the feeling of use as non greasy, but the detailed method of synthesis, yield, etc. Not listed. Further, a diether / monoester form of glycerin in which one ether group of glycerin triether is substituted with an ester group is disclosed as a low-calorie lipid in Canadian Patent No. 1106681. However, regarding the synthetic method, a step of reacting an alcohol with epihalohydrin in the presence of a Lewis acid such as tin tetrachloride or boron trifluoride to obtain an alkylhalohydrin, and further treating it with an alkali to form a ring-closed alkylglycidyl The step of obtaining an ether, and again reacting with an alcohol in the presence of a Lewis acid such as tin tetrachloride or boron trifluoride to give 1,3-di-
The diether / monoester form of glycerin is obtained by a four-step synthetic route including a step of obtaining O-alkylglycerin and a step of reacting it with a fatty acid to obtain a diether / monoester form of glycerin.

As another method for synthesizing 1,3-di-O-alkylglycerin, for example, Ber., 24, 2145 (1891), J. C.
hem. Soc., 101, 305 (1912) by reacting phenols with epichlorohydrin under alkaline conditions,
A method for obtaining 1,3-di-O-alkylglycerin in one step is described. However, the acidity of the phenols and that of the fatty alcohols are clearly different, and as seen in the above-mentioned Canadian patent, it is considered that it is difficult to obtain 1,3-O-dialkylglycerin in one step with the fatty alcohols. It was being done.

[0005]

The above-mentioned diether / monoester form of glycerin is a general-purpose oil agent because it is difficult to manufacture, while it is expected to improve the feel and the like due to the reduction of ester bonds as compared with glycerine triester. However, the development of an easy manufacturing method is desired. Therefore, an object of the present invention is to provide a simple method for producing a glycerin derivative useful as a cosmetic oil having a low stickiness and an excellent feel.

[0006]

Means for Solving the Problems In order to solve the above-mentioned problems, the present inventors have earnestly studied on a simple method for producing a diether / monoester body of glycerin used as an oily agent having an excellent feeling, and as a result, It was found that by reacting an alcohol with epihalohydrin in the presence of a base, a 1,3-diether form of glycerin can be obtained in one step, and a diether / monoester form of glycerin can be easily obtained by esterifying this. The present invention has been completed. That is, the present invention provides the following general formula (1) R ₁ —OH (1) (wherein R ₁ represents a linear or branched alkyl group having 1 to 24 carbon atoms, an alkenyl group or a cyclic alkyl group). .)
One or more alcohols represented by (hereinafter abbreviated as alcohol (1)) and the following general formula (2)

[0007]

[Chemical 4]

An epihalohydrin represented by the formula (wherein X represents a halogen atom) (hereinafter abbreviated as epihalohydrin (2)) is reacted in the presence of a base to give the following general formula (3):

[0009]

[Chemical 5]

(In the formula, R ₁ has the same meaning as described above, and 2
The two R _1's may be the same or different. ) Is obtained (hereinafter abbreviated as compound (3)), and this compound (3) is further added with the following general formula (4) R ₂ —COOR ₃ (4) (wherein R ₂ is a carbon atom). A fatty acid represented by the formula 1 to 23, which is a linear or branched alkyl group or alkenyl group, and R ₃ is a hydrogen atom, a methyl group or an ethyl group, or an ester thereof (hereinafter fatty acid or ester (4)) Abbreviated as),
Alternatively, an acid chloride represented by the following general formula (5) R ₂ —COCl (5) (wherein R ₂ has the same meaning as described above) (hereinafter abbreviated as acid chloride (5)) is reacted. The following general formula (6) is characterized by

[0011]

[Chemical 6]

A method for producing a glycerin derivative represented by the formula (wherein R ₁ and R ₂ have the same meanings as described above) (hereinafter abbreviated as glycerin derivative (6)) is provided.

The present invention will be described in detail below. In the present invention, first, as shown in the following reaction formula, an alcohol (1) and an epihalohydrin (2) are reacted in the presence of a base to give a compound (3) which is an intermediate of the glycerin derivative (6). ) Is manufactured.

[0014]

[Chemical 7]

(In the formula, R ₁ and X have the same meanings as described above.) In the above general formula (1), the group represented by R ₁ is, for example,
Methyl group, ethyl group, n-propyl group, n-butyl group,
n-hexyl group, n-heptyl group, n-octyl group, n
-Decyl group, n-dodecyl group, n-tetradecyl group, n
-Straight chain alkyl group such as hexadecyl group and n-octadecyl group, isopropyl group, t-butyl group, 2-ethylhexyl group, 2-hexyldecyl group, 2-heptylundecyl group, 2-octyldodecyl group, 2-decyl group Tetradecyl group, 5,7,7-trimethyl-2- (1,3,3-trimethylbutyl) octyl group, the following formula

[0016]

[Chemical 8]

A branched alkyl group such as a methyl-branched isostearyl group represented by the formula (wherein m + n = 14 and a distribution having m = n = 7 as a vertex), an allyl group, a methallyl group,
Examples thereof include alkenyl groups such as 9-octadecenyl group and farnesyl group, and cycloalkyl groups such as cyclooctyl group, cyclododecyl group and abiethyl group, but are not limited thereto. Preferred as R ₁ is a linear, branched or cyclic alkyl group having 2 to 12 carbon atoms.

Examples of the alcohol (1) used in the present invention include those having an R ₁ group as described above, and specific examples include methyl alcohol, ethyl alcohol, n-propyl alcohol, n-butyl alcohol, Linear alcohols such as n-hexyl alcohol, n-heptyl alcohol, n-octyl alcohol, n-decyl alcohol, n-dodecyl alcohol, n-tetradecyl alcohol, n-hexadecyl alcohol and n-octadecyl alcohol, isopropyl alcohol, t-butyl alcohol, 2-ethylhexyl alcohol, 2-hexyldecyl alcohol, 2-heptylundecyl alcohol, 2
-Octyl dodecyl alcohol, 2-decyl tetradecyl alcohol, 2- (1,3,3-trimethylbutyl)
-5,7,7-trimethyloctyl alcohol, the following formula

[0019]

[Chemical 9]

(Wherein, m and n have the same meanings as described above), branched alcohols such as methyl-branched isostearyl alcohol, allyl alcohol, methallyl alcohol, 9-octadecenyl alcohol, farnesyl alcohol. Examples thereof include alkenyl alcohols such as, cyclooctyl alcohol, cyclododecyl alcohol, and cyclic alcohols such as abiethyl alcohol, but are not necessarily limited thereto. Preferred is a linear, branched or cyclic alcohol having 2 to 12 carbon atoms. These alcohols can be used alone or as a mixture of two or more.

Epihalohydrin used in the present invention (2)
Examples thereof include epihalohydrin in which X represents a chlorine, bromine or iodine atom, and epichlorohydrin is preferable.

In the present invention, the alcohol (1) and the epihalohydrin (2) are reacted in the presence of a base. Examples of the base used here include hydroxides of alkali metals such as potassium hydroxide and sodium hydroxide; carbonates of alkali metals such as potassium carbonate and sodium carbonate; hydrides of alkali metals such as sodium hydride; butyl. Examples thereof include alkylated products of alkali metals such as lithium, and potassium hydroxide and sodium hydroxide are preferable. The base may be in the form of particles, pellets or an aqueous solution, but is preferably in the form of particles or pellets. In this reaction, a phase transfer catalyst such as tetrabutylammonium bromide or tetrabutylammonium chloride may be used depending on the case.

The amount of alcohol (1) with respect to epihalohydrin (2) in this reaction is preferably 1 to 1000 times equivalent,
More preferably, it is 2 to 100 times equivalent. If the amount is less than 1 equivalent, the yield of compound (3) will be reduced. Also alcohol
The larger the amount of (1), the higher the yield (selectivity) of compound (3).
Will improve. The excess alcohol (1) can be recovered and reused, but 1000 times equivalent or less is sufficient. The amount of base used in this reaction is epihalohydrin.
The amount is preferably 0.5 to 10 times equivalent, and more preferably 0.8 to 5 times equivalent to (2). If it is less than 0.5 times equivalent, the reaction proceeds slowly, and if it is more than 10 times equivalent, the compound (3)
From which the reaction has proceeded further, and many side reaction products are generated, which is not preferable.

In this reaction, the desired compound (3) can be obtained by charging the alcohol (1), the epihalohydrin (2) and a base all at once, but preferably the alcohol (1) and the base are used in the first step. It is more efficient and yield is improved by adding epihalohydrin (2) after sufficiently generating alcoholate. The first step is the reaction between alcohol (1) and a base. If the combination is such that alcoholate can be easily generated, it is sufficient to stir at low temperature or room temperature. Or if it is a pelletized alkali hydroxide, stir for about 1 hour at a temperature of about 30 to 100 ° C to dissolve the alkali sufficiently,
Alcoholate is preferred. The stirring temperature varies depending on the type of alcohol (1), but if it is lower than 30 ° C, the generation of alcoholate is not sufficient. Further, it is sufficient that the base is dissolved, and it is not necessary to raise the temperature above 100 ° C. Here, the reaction proceeds sufficiently even without using a solvent, but hexane, benzene, toluene, xylene and the like can be used depending on the case.

Regarding the next reaction with epihalohydrin (2), if the sufficient alcoholate is generated in the first step, epihalohydrin (2) may be added all at once, but it is preferable to add it over 30 minutes to 3 hours. preferable. The reaction here depends on the alcohol used in the first step, but the reaction can be performed at about 10 to 90 ° C. In particular, when using an alcohol with a particularly low molecular weight such as methyl alcohol, 10
It is preferable to carry out at about 40 ° C. If it is lower than 10 ° C, the reaction proceeds slowly, but if it exceeds 40 ° C, a side reaction proceeds.
Also, if the carbon number of the alcohol exceeds 10, the reaction temperature will be
40-90 degreeC is preferable. If the temperature is lower than 40 ° C, the reaction will be slow and
If it exceeds 90 ° C, a large amount of by-products will be produced. Reaction time is 1
~ 5 hours is sufficient.

Next, the compound (3) thus obtained
In addition, as shown in the following reaction formula, fatty acid or its ester
The glycerin derivative (6) can be obtained by reacting (4) or the acid chloride (5).

[0027]

[Chemical 10]

(In the formula, R ₁ , R ₂ and R ₃ have the same meanings as described above.) A fatty acid or its ester (4) which is reacted with the compound (3)
Or as the fatty acid forming the acid chloride (5),
Acetic acid, butyric acid, caproic acid, caprylic acid, pelargonic acid,
Linear fatty acids such as capric acid, undecanoic acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, and lignoceric acid, 2-ethylhexanoic acid, 3,5,5-trimethylhexanoic acid, 2- (1,
3,3-trimethylbutyl) -5,7,7-trimethyloctanoic acid, the following formula

[0029]

[Chemical 11]

(Wherein m and n have the same meanings as described above), branched fatty acids such as methyl-branched isostearic acid, 9-hexadecenoic acid, 9-octadecenoic acid, 1
Examples of unsaturated fatty acids such as 3-docosenoic acid include
It is not necessarily limited to these.

Compound (3) and fatty acid or ester thereof
In the reaction with (4), paratoluenesulfonic acid, sulfuric acid, hydrochloric acid, boron fluoride etherate and the like are added all at once in the presence of an acid catalyst to react. Here, when a fatty acid is used, water is taken out, and when a fatty acid ester is used, methanol or ethanol is taken out of the system to produce the glycerin derivative (6). In this case, a solvent such as benzene, toluene, or xylene may be used to react with the solvent under azeotropic reflux (80 to 130 ° C) to extract water or methanol or ethanol, or at a high temperature (200
It is also possible to directly react the compound (3) with the fatty acid or its ester (4) at a temperature of not less than 0 ° C, preferably 200 to 250 ° C, without using a solvent, and then water or methanol or ethanol can be drawn out. The reaction time is preferably about 1 to 15 hours. In addition, in the reaction of the compound (3) with the acid chloride (5), if necessary, in the presence of a base catalyst such as pyridine, dimethylaniline, triethylamine, tetramethylurea, etc., in a solvent such as diethyl ether, tetrahydrofuran, 0 to 100
Direct esterification can be carried out at ℃ or under solvent reflux. The reaction time is about 1 to 10 hours.

In these reactions, the compound (3) and a fatty acid or its ester (4), or an acid chloride (5)
Is sufficient to react 1 to 2 equivalents of fatty acid or its ester (4) or acid chloride (5) with respect to compound (3). When the amount is less than 1-fold equivalent, at least unreacted compound (3) is recovered. Further, if the amount used is more than twice the equivalent, the esterification proceeds considerably, but a large amount of unreacted fatty acid or its ester (4) or acid chloride (5) will be recovered, which is economically undesirable. . It is preferably 1 to 1.5 times equivalent.

The glycerin derivative (6) obtained by the simple production method of the present invention is useful as an oil agent for cosmetics. According to the method of the present invention as described above, the glycerin derivative (6)
R ₁ and R ₂ give various compounds,
As far as cosmetic oils are concerned, those having a molecular weight of 100 to 600 are preferable. If the molecular weight is less than 100, it may cause an odor,
There may also be safety issues. On the other hand, if it is more than 600, the viscosity becomes considerably high and the oily feeling becomes strong, so that it is not preferable as an oily agent for cosmetics in terms of feel. More preferably, it has a molecular weight of 200 to 500.

[0034]

The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

Example 1 2-O-dodecyloyl-1,3-di-O-methylglycerin (6a)

[0036]

[Chemical 12]

A 5 liter flask equipped with a dropping funnel, a nitrogen gas introducing tube, a cooling tube and a stirrer was charged with 2880 g (90 mol) of methyl alcohol and 432 g (10.8 mol) of particulate sodium hydroxide under nitrogen gas introduction. The mixture was stirred at 60 ° C for 1 hour. Then, the mixture was cooled to 30 ° C., 832 g (9.0 mol) of epichlorohydrin was added dropwise over 2 hours, and after completion of the addition, the mixture was further stirred at 30 ° C. for 3.5 hours. The reaction mixture was neutralized with hydrochloric acid, filtered, and then excess methyl alcohol was distilled off.
Further vacuum distillation (68 ° C / 10 Torr) was performed to remove the intermediate 1,3-di-O-methylglycerin of the title compound.
91 g (yield 73%; based on epichlorohydrin) was obtained.

Next, 300 g (2.5 mol) of 1,3-di-O-methylglycerin obtained above was placed in a 2 liter flask equipped with a nitrogen gas introduction tube, a cooling dehydration tube and a stirrer.
Lauric acid (660 g, 3.3 mol), xylene (500 g) and paratoluenesulfonic acid (3 g, 0.017 mol) were charged, and dehydration esterification was carried out for 8 hours while refluxing xylene under introduction of nitrogen gas.
Thereafter, the product was washed with water, xylene and lauric acid were distilled off under reduced pressure, and further distilled under reduced pressure (147 ° C / 0.7 Torr) to give 680 g of the title compound as a colorless transparent liquid (yield 90
%) Was obtained.

Example 2 2-O-octanoyl-1,3-di-O-butylglycerin (6b)

[0040]

[Chemical 13]

A 5 liter flask equipped with a dropping funnel, a nitrogen gas introducing tube, a cooling tube and a stirrer was charged with 2904 g (39.2 mol) of n-butyl alcohol and 575 g (14.4 mol) of particulate sodium hydroxide, The mixture was stirred at 80 ° C for 1 hour while introducing nitrogen gas. Then, the mixture was cooled to 60 ° C., 889 g (9.6 mol) of epichlorohydrin was added dropwise over 1 hour, and after completion of the addition, the mixture was further heated with stirring at 60 ° C. for 2 hours. The reaction mixture was washed with water to remove sodium hydroxide, excess n-butyl alcohol was distilled off under reduced pressure, and further distilled under reduced pressure (105 to 115 ° C / 5 Torr) to give Intermediate 1 of the title compound. , 3-di-O-butylglycerin
1005 g (51% yield; based on epichlorohydrin) was obtained.

Next, 400 g (1.96 mol) of 1,3-di-O-butylglycerin obtained above was placed in a 1-liter flask equipped with a nitrogen gas introduction tube, a cooling dehydration tube and a stirrer.
Octanoic acid (324 g, 2.25 mol) was charged, and dehydration esterification was carried out at 220 ° C. for 12 hours under introduction of nitrogen gas. afterwards,
Wash with water, and then distill off excess octanoic acid under reduced pressure.
Further, by vacuum distillation (160 ° C / 1 Torr), 595 g (yield 92%) of the title compound was obtained as a colorless transparent liquid.

Example 3 2-O-2-ethylhexanoyl-1,3-di-O-butylglycerin (6c)

[0044]

[Chemical 14]

250 g (1.2 mol) of 1,3-di-O-butylglycerin obtained in Example 2 was added to a 2 liter flask equipped with a nitrogen gas introduction tube, a cooling dehydration tube and a stirrer. 229 g (1.6 mol) of ethylhexanoic acid, 17.9 g (0.1 mol) of p-toluenesulfonic acid and 300 g of toluene were charged, and dehydration esterification was carried out under a nitrogen gas introduction while refluxing toluene for 9.5 hours. After that, washing with water, further distilling off toluene and 2-ethylhexanoic acid under reduced pressure, and further distilling under reduced pressure (165 to 170 ° C./5 Torr), 412 g (yield 96%) of the title compound was obtained as a colorless transparent liquid. Obtained.

Example 4 2-O-Octanoyl-1,3-di-O-octylglycerin (6d)

[0047]

[Chemical 15]

In a 3 liter flask equipped with a dropping funnel, a nitrogen gas introducing tube, a cooling tube and a stirrer, 1950 g (15 mol) of octyl alcohol and 240 g of particulate sodium hydroxide.
(6 mol) was charged, and the mixture was stirred at 80 ° C. for 1 hour under introduction of nitrogen gas. Then, at 80 ° C, epichlorohydrin 277.6g (3mol)
Was added dropwise over 1.5 hours, and after the addition was completed, it was further heated at 80 ° C for 3
Stir for hours. The reaction mixture was washed with water to remove sodium hydroxide, excess octyl alcohol was distilled off under reduced pressure, and further distilled under reduced pressure (150 to 160 ° C./0.25 Torr) to give Intermediate 1 of the title compound. 556 g (yield 60%; based on epichlorohydrin) of 3-di-O-octylglycerin was obtained.

Next, 150 g (0.47 mol) of the 1,3-di-O-octylglycerin obtained above was placed in a 500 ml flask equipped with a nitrogen gas inlet tube, a cooling dehydrator and a stirrer.
, Octanoic acid 75.2 g (0.52 mol), paratoluene sulfonic acid 8.9 g (0.047 mol) and toluene 100 g were charged, and dehydration esterification was carried out for 3.5 hours while refluxing toluene under introduction of nitrogen gas. After that, it is washed with water, toluene and octanoic acid are further distilled off under reduced pressure, and further distilled under reduced pressure (Smith distillation:
At 240 ° C./0.3 Torr), 193 g (yield 93%) of the title compound was obtained as a colorless transparent liquid.

Example 5 2-O-octanoyl-1,3-bis-O- (2-ethylhexyl) glycerin (6e)

[0051]

[Chemical 16]

Into a 3 liter flask equipped with a dropping funnel, a nitrogen gas introducing tube, a cooling tube and a stirrer was charged 2600 g (20 mol) of 2-ethylhexyl alcohol and 400 g (10 mol) of particulate sodium hydroxide, and nitrogen gas was added. The mixture was stirred at 80 ° C for 1 hour. Then, the mixture was cooled to 50 ° C., and 427 g (5 mol) of epichlorohydrin was added dropwise over 30 minutes. After completion of the addition, the temperature was raised from 50 ° C. to 70 ° C. and the mixture was heated and stirred for 4.5 hours. The reaction mixture was washed with water to remove sodium hydroxide, the excess 2-ethylhexyl alcohol was distilled off under reduced pressure, and further distilled under reduced pressure to give the intermediate 1,3-bis-O- (2- of the title compound. Ethylhexyl) glycerin 689 g (44% yield; epichlorohydrin standard)
Got

Next, the 1,3-bis-O- (2-ethylhexyl) glycerin obtained above was placed in a 500 ml flask equipped with a nitrogen gas inlet tube, a cooling dehydrator and a stirrer.
100 g (0.3 mol), 47 g (0.33 mol) of octanoic acid, 5.6 g (0.029 mol) of paratoluenesulfonic acid, and 100 g of toluene were charged, and dehydration esterification was carried out for 4.5 hours while refluxing toluene under introduction of nitrogen gas. Then, the product was washed with water, toluene and octanoic acid were distilled off under reduced pressure, and further distilled under reduced pressure (Smith distillation: 240 ° C / 0.3 Torr) to obtain 126 g of the title compound as a colorless transparent liquid (yield 95%). It was

Example 6 2-O-isostearoyl-1,3-di-O-octylglycerin (6f)

[0055]

[Chemical 17]

(In the formula, m and n have the same meanings as described above.) 500 equipped with a nitrogen gas introduction pipe, a cooling dehydration pipe and a stirring device
The 1,3-di-O-obtained in Example 4 was added to a ml flask.
Octyl glycerin 94.8 g (0.3 mol), isostearic acid (Emery Co .: Emazole 871) 98 g (0.35 mol), para-toluenesulfonic acid 2.85 g (0.015 mol), toluene 150 g were charged, and under reflux of toluene under nitrogen gas introduction, Dehydration esterification was performed for 5 hours. Then, it was washed with water, toluene was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 169 g (yield 97%) of the title compound as a colorless transparent liquid.

Each of the glycerin derivatives obtained in Examples 1 to 6 was a cosmetic oil having a low stickiness and an excellent feel.

─────────────────────────────────────────────────── --Continued from the front page (56) References JP-A-1-268663 (JP, A) JP-A-1-93558 (JP, A) JP-A-63-307843 (JP, A) JP-B-44- 26672 (JP, B1) JP-B 35-4964 (JP, B1) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07C 67/08, 67/03, 67/14 C07C 69/30 C07C 41 / 03,41 / 16 C07C 43 / 10,43 / 184 CA (STN) CAOLD (STN) REGISTRY (STN)

Claims (2)

(57) [Claims] 1. The following general formula (1) R ₁ —OH (1) (In the formula, R ₁ represents a linear or branched alkyl group having 1 to 24 carbon atoms, an alkenyl group or a cyclic alkyl group. )
One or more alcohols represented by the following general formula (2) (Wherein X represents a halogen atom) is reacted with an epihalohydrin represented by the following general formula (3): (In the formula, R ₁ has the same meaning as described above, and two R ₁ may be the same or different.), And the compound represented by the following general formula (4) R ₂ —COOR ₃ (4) (in the formula, R ₂ represents a linear or branched alkyl group or alkenyl group having 1 to 23 carbon atoms, and R ₃ represents a hydrogen atom, a methyl group or an ethyl group). Or a fatty acid ester thereof, or an acid chloride represented by the following general formula (5) R ₂ —COCl (5) (wherein R ₂ has the same meaning as described above). The following general formula
(6) [Chemical 3] (In the formula, R ₁ and R ₂ have the same meanings as described above.) A method for producing a glycerin derivative. 2. The method according to claim 1, wherein the base is an alkali metal hydroxide, carbonate, hydride or alkylated product.