JPH0249750A - Production of omega-hydroxy-fatty acid ester - Google Patents

Abstract

PURPOSE:To readily obtain the subject compound useful as a synthetic intermediate for cyclic lactones used as a raw material for medicines, etc., in high yield by reducing a diacid monoester available at a relatively low cost as a raw material with a quaternary ammonium borohydride. CONSTITUTION:An alkanedioic acid is esterified with an alcohol and esterified with Ba(OH)2 to provide a mono salt, which is substituted with an acid, etc., to readily afford a diacid monoester expressed by formula I (R is alkyl; n is a natural number), such as monomethyl undecane-1,11-dicarboxylate, which is then reduced with a quaternary ammonium borohydride expressed by formula II (R<1> to R<4> are alkyl, aralkyl or aryl), such as tetra-n-butylammonium borohydride, preferably in the coexistence of an organic halide, such as CCl4, at ambient temperature to provide the objective compound, such as methyl 13-hydroxytridecanoate, useful as a synthetic intermediate for cyclic lactones utilized as a perfume, etc.

Description

[Detailed Description of the Invention] The present invention relates to the present invention, which is directed to the use of omega chestnuts useful as intermediates for synthesizing cyclic lactones used as raw materials for pharmaceuticals or fragrances.
-Regarding a method for producing hydroxy fatty acid ester.

The conventional method for producing ω-hydroxy fatty acid esters from 2-monoesters of Junmai and Ueda Rui Bean is to use diborane as a reducing agent to directly reduce the 2-monoesters to ω-hydroxy fatty acid esters [Journal of Chemical Education (Journal of Chemical)
Education) 54.12, p778-779 (
1977) ) is known.

On the other hand, as a method for producing ω-hydroxy fatty acids,
ω-hydroxy-alkyl-γ-butyrolactone or ω-acyloxy-alkyl-γ-butyrolactone,
A method of supplying hydrogen gas in the presence of a hydrogen cracking catalyst to carry out a catalytic reaction (Japanese Patent Publication No. 613776) or 13-oxa-bicyclo(10,4,0)-hexadecene (1(1
2) A method has been proposed in which the lactone is converted into a lactone and the lactone ring is opened by the Wolffukisiner method or the Van-Misolon method (Japanese Patent Publication No. 21474/1983).

However, in the method of producing dimonoesters by reduction using diborane, diborane is very expensive and dangerous to handle, and furthermore, the reaction selectivity is low and the yield of the target ester is low. Not economical for industrial scale production. In addition, all of the above methods for producing ω-hydroxy fatty acids use expensive and complicated compounds as starting materials, resulting in a problem of high production costs.

An object of the present invention is to provide a production method for advantageously producing ω-hydroxy fatty acid esters in high yield from dimonoesters that are available at relatively low cost. .

The present invention will be explained in detail below.

The characteristics of the present invention are represented by the general formula % (1) [wherein R represents an alkyl group and n represents a natural number]. ) A dimonoester represented by the general formula % ( ) [wherein RIXRZ, R3, and R4 each represent an alkyl group, an aralkyl group, or an aryl group, which may be different from each other. ] It is reduced with quaternary ammonium borohydride represented by the general formula % formula % [[] [wherein R and n represent the same meanings as above. The object of the present invention is to obtain an ω-hydroxy fatty acid ester represented by the following formula.

In the present invention, the general formula (r) used as a starting material is
) can be easily obtained by esterifying an alkanedioic acid with an alcohol, converting the ester into a monosalt of barium using, for example, barium hydroxide, and then replacing the barium salt with an acid. Obtainable.

In this case, as the alcohol for the above esterification,
It is preferable to use a lower alcohol having 1 to 4 carbon atoms because the resulting esterified product can be easily separated and purified.

In addition, as the dimonoester, when the purpose is an intermediate for obtaining a lactone used as a raw material for pharmaceuticals or a fragrance, an alkanedioic acid monoester having 9 to 18 carbon atoms is preferable.

The present invention is to reduce a dimonoester represented by the general formula (I) using a quaternary ammonium borohydride represented by the general formula (old).Quaternary ammonium borohydride is also available industrially. Although possible, it can also be easily produced from, for example, quaternary ammonium halide or quaternary ammonium sulfate and alkali metal borohydride.

(M, D, Banus, R, W, Bragden a
nd T, R, P, Grbb Jr.

J,Am,Chem,Soc,,74(2346)19
52; A, Br', 1ndstr; m, U, Jung
gren and B, Lamm, Tetrahe
Dron Lett.

Examples of quaternary ammonium borohydrides that can be used include tetramethylammoniumborohydridetetraethyltetrapropyl, tetrabutyltetrapentyltetrahexyltetraoctyltetradecyltetrahexadecyl, and tetrabenzyltetraphenylbutyltrimethyldodecyltrimethylhexadecylmethyltriethyldodecyltriethylhexadecyl. Triethyl 〃 Nonyltripropyl 〃 Decyltributyl 〃 Hexadecyltributyl 〃 Benzyltrimethylbenzyltriethyl 〃 Hensyltripropylbenzyltributylmethyltrioctyl 〃 Phenyltrimethylphenyltriethylphenyltributylbenzylbutyldimethyl 〃 Benzylphenyldimethyl 〃 Benzylhexadecadimethyl〃 etc. can be exemplified.

The amount of quaternary ammonium borohydride used is determined according to the general formula (
The amount can be selected from a range of 0.6 to 1.5 equivalents relative to the dimonoester represented by I).

When carrying out the present invention, it is preferable to carry out the process in the presence of an organic halide in terms of yield and reaction efficiency. Examples of organic halides include methylene chloride, chloroform, carbon tetrachloride, dichloroethane, trichlene, and methyl iodide. , ethyl bromide and the like.

The amount of organic halide used is not particularly limited, and it can also serve as a solvent.

The reaction proceeds at around room temperature, but may be heated or cooled if desired. A temperature of 150°C or higher is undesirable because selectivity decreases, and a temperature of -20°C or lower is undesirable because reaction efficiency decreases.

As described above, by reducing a dimonoester with quaternary ammonium borohydride, an ω-hydroxy fatty acid ester can be obtained in high yield.

The ω-hydroxy fatty acid ester thus obtained is polymerized to form a linear polyester by a known method, and this is heated and depolymerized in the presence of a depolymerization catalyst to form a cyclic lactone. Can be done.

The present invention will be specifically explained below using Examples.

Example 1 Tetra n-butylammonium polyhydride (2601
11g.

1.01 mmol) was dissolved in undecane-1,11-dicarboxylic acid monomethyl ester (259 mg, 1.00 mmol).
The mixture was added to a dry carbon tetrachloride (9n+1!) solution of ol) and stirred at room temperature for 2.5 hours. After adding 2N hydrochloric acid to the reaction solution to make it acidic, the organic layer was separated. Chloroform was added to the aqueous layer for extraction, and both organic layers were combined and dried over anhydrous magnesium sulfate. After filtration and concentration, silica gel column chromatography (10% ether-methylene chloride)
The mixture was separated and purified to obtain 13-hydroxytridecanoic acid methyl ester (225 mg, 92%).

White plate-like crystal m, p, 30.0-31.0℃TR
(cn+-'): 3300.2945.2875
．． 1745.1470.1435.1180.1040'HN M R (CDCIz, 90MHz):61.
15-1.90 (m, 20H, -CHz-), 2.28
(t, 7Hz, 2H+-Cth-C-), 3.64(t
, 7tlz, 211. -C1bOH), 3.65(
s, 3t1. -OCIh) Mass m/z (%): 245 (M”+1.1.0), 226 (3,2)
, 214 (43,9), 195 (9,4), 194 (7
,6), 166(6,0), 152(11,1)
, 143 (22,7) 112 (30,5), 98 (1
00), 87 (100), 84 (68,0), 7
4 (100), 69 (93,9), 55 (100), 4
3 (60,2), 41 (100) Example 2 2.29 (t, 7 Hz, 2H, -Ctlz-C-), tetra n-butylammonium borohydride (263 mg
.

1.02 mmol) and tetradecane-1,14-dicarboxylic acid monomethyl ester (302 mg, 1.01
The reaction mixture was added to a solution of dry carbon tetrachloride (9ml) and stirred at room temperature for 2.5 hours. After the reaction, it was post-treated in the same manner as in Example 1, and then purified to give 16-hydroxydihexadecanoic acid methyl ester (221mg). , 77%).

White plate-like crystals m, p, 66.5-67.0°C [Reference m, 9. 55-55.5℃ "Dictionary of Organic Co Compound"
mpound) vol, 3. (1965)) I R(cffi-'): 3100.2925.
2860.1740.1715.1465.1430.
1175'HNMR (CDC13, 90MHz): 61.10
~1.87 (m, 26)1. -CHz-), 3.62(
t, 7Hz, 211. -C1hOI+), 3.64
(s, 3H, -OCtlz) Mass mHz (%): 286 (M", 1.3), 268 (10, 1)
, 256 (79,7), 237 (11,3) , 23
6(19,7), 208(5,4), 194(
10,8), 166(5,7), 152(10
,0), 143(27,4), 112(40,4)
, 98 (100), 87 (100), 84 (87,3)
, 74 (100), 69 (too), 55 (100
)43(100), 4H100).

Example 3 Tetra n-butylammonium borohydride (258,
0mg.

1.00 mmol) and tridecane-1,13-dicarboxylic acid monomethyl ester (287.1 mg, 1.0
Methyl iodide (0,125 ml) was added to a dry methylene chloride solution (1 mg) of 0 mmol) under an argon gas atmosphere.
! , 2.0 mmol) was added dropwise, and the mixture was stirred at room temperature for 2 hours. After the reaction was completed, 2N hydrochloric acid was added to the solution to make it acidic.
The organic layer was separated. Add ethyl acetate to the aqueous layer and extract
Both organic layers were combined, washed with saturated brine, and then dried over sodium sulfate.

After concentration under reduced pressure, the obtained crude product was separated and purified by column chromatography to obtain the desired 15-hydroxypentadecanoic acid methyl ester (248.5 mg, 91%).

mp, 40-42℃ [Literature, mp, 31.8-32
．． 4℃ [Helveti force Chimi force Acta J ()Ielv,
Chim, ^ctaH2, I R(c+w-'):
3430.2930.2850.1740.1465.
1435.1195.1170.10105ON (
CDCh, 90MHz): δ 1.25 (m, 20H)
, 1.58 (m, 411), 2.30 (t, 2H)
, 3.64(t, 3+-+), 3.67(s, 3H)M
ass (70ev) mHz (%): 273 (
M"+1.1.2), 273(M"-H2O,1,3
) 242(14,0), 143(10,2), 129(
5,7), 125 (4,7), 112 (13,6), 9
8 (47,0), 97 (15,9), 87 (49,8)
, 84 (28,9), 81 (12,2), 74 (100
), 55 (56,1) Example 4 Tetra n-butylammonium borohydride (257,
3 mg 1.00 mmol) and tridecane-1,13-
Dicarboxylic acid monomethyl ester (286.8 mg,
1.00 mmol) was transferred to a reaction vessel, dry carbon tetrachloride (1 m j!) was added under an argon gas atmosphere, and the mixture was stirred at room temperature for 3 hours. After the reaction was completed, water was added, diluted with methylene chloride, and the organic layer was separated. Methylene chloride was added to the aqueous layer for extraction, and both organic layers were combined, washed with 2N hydrochloric acid and saturated brine, and dried over sodium sulfate. After vacuum concentration,
A portion of the obtained crude product was taken and quantitatively determined by gas chromatography (internal standard method).
-Hydroxypentadecanoic acid methyl ester C243m
g, 89%) was found to be produced.

Example 5 Tetra n-butylammonium borohydride (258,
5mg.

1.01 mmol) and tridecane-1,13-dicarboxylic acid monomethyl ester <286.6 mg, 1. O
Ommol) was placed in a reaction vessel, dry carbon tetrachloride (1 m e ) was added under an argon gas atmosphere, and the mixture was heated at 55°C for 4 hours.
Stir for hours. After the reaction was completed, post-treatment was carried out in the same manner as in Example 4, and the obtained crude product was separated and purified by column chromatography to obtain the desired 15-hydroxypentadecanoic acid methyl ester (236 mg, 87%). .

Example 6 Tetramethylammonium borohydride (9
1,IIwg,! , 02 a+mol) and tridecane-1,13-dicarboxylic acid monomethyl ester (286
, 1 mg, 1. OOmmol) and added dry carbon tetrachloride (3 mIt) under an argon gas atmosphere.
The mixture was heated and stirred at ℃ for 22 hours. After the reaction, the desired 15-hydroxy Pentadecanoic acid methyl ester (210 mg, 7
7%).

Example 7 Dodecyltrimethylammonium borohydride (245
,0mg, 1.01 mmol) and tridecane-1,1
3-dicarboxylic acid monomethyl ester (287.0 mg
, ],,00 mmol) was transferred to a reaction vessel, and dry carbon tetrachloride (2 ml) was added under an argon gas atmosphere.
The mixture was heated and stirred at 80°C for 18 hours. After the reaction, post-treatment was carried out in the same manner as in Example 14, and the obtained crude product was quantitatively determined by gas chromatography (internal standard method).
1 mg, 81%) was found to be produced.

Example 8 Triethylbenzylammonium borohydride (265
,0mg, 1.28 mmol) and tridecane-1,
13-dicarboxylic acid monomethyl ester (352,0m
g, 1 mol at 1.23° C.) was transferred to a reaction vessel, dry carbon tetrachloride (In 12 ) was added thereto under an argon gas atmosphere, and the mixture was heated and stirred at 70° C. for 18 hours. After the reaction, post-treatment was carried out in the same manner as in Example 1, and the obtained crude product was quantitatively determined by gas chromatography (internal standard method).
88 mg, 86%) was found to be produced.

Example 9 Tetraethylammonium borohydride (
145,5111 g, 1.00 mmol) and tridecane-1,13 dicarboxylic acid monomethyl ester (28
6.0mg, 1. After the reaction, post-treatment was carried out in the same manner as in Example 1, and the resulting crude product was was determined by gas chromatography (internal standard method), and the target 15-hydroxypentadecanoic acid methyl ester (214 mg, 79%) was obtained.
was found to be generated.

Example 1 Benzylroot butylammonium borohydride (293
,7mg, 1.01mmol) and tridecane-1
, 13-dicarboxylic acid monomethyl ester (285,6
mg, 1.00 mmol) into a reaction vessel, add dry carbon tetrachloride (2 ml) under an argon gas atmosphere, and add 70 mmol of dry carbon tetrachloride.
The mixture was heated and stirred at ℃ for 5.5 hours. The reaction solution was cooled to room temperature, water was added, and the remaining organic layer was separated. Toluene was added to the aqueous layer for extraction, and both organic layers were combined, washed with 2N hydrochloric acid and saturated brine, and dried over sodium sulfate. After concentration under reduced pressure, the resulting crude product was quantified by gas chromatography (internal standard method), and it was found that the desired 15-hydroxypentadecanoic acid methyl ester (225 mg, 83%) had been produced.

Claims (2)

[Claims] (1) A diacid monoester represented by the general formula HOCO(CH_2)_nCOOR^ [in the formula, R^ represents an alkyl group and n represents a natural number], a diacid monoester represented by the general formula R^1R^2R^3R^4NBH_4 [formula In the formula, R^1, R^2, R^3, and R^4 each represent an alkyl group, an aralkyl group, or an aryl group, which may be different from each other. ] A method for producing an ω-hydroxy fatty acid ester, which comprises reducing the ω-hydroxy fatty acid ester with a quaternary ammonium borohydride represented by: (2) The method according to claim (1), wherein the reduction is carried out in the presence of an organic halide.