JP2016204298A - Manufacturing method of threo type long chain 1,3-alkanediol - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a high yield, inexpensive and industrially useful manufacturing method of a threo type long chain 1,3-alkanediol which is an important compound for general purpose chemical, bioactive substrate such as a monomer for functional polymer or an intermediate for medical agricultural chemical raw material or the like.SOLUTION: There is provided a method for manufacturing a threo type long chain 1,3-alkanediol represented by the formula (1) with 15 to 25 carbon atoms with good yield with purity of 99% or more by recrystallization from 1,3-alkanediol with threo:erythro ratio of 30/70 to 70/30 by using a mix solvent having volume ratio of hexane/ethylene acetate of 90/0 to 60/40. (1), where Rand Rare C5 to 17 alkyl group or alkenyl group.SELECTED DRAWING: None

Description

  The present invention relates to a method for producing a threo-type long-chain 1,3-alkanediol. The threo-type long chain 1,3-alkanediol obtained by the production method of the present invention is useful as a raw material for antifoaming agents, pharmaceuticals, agricultural chemicals, fragrances, various chemicals, resins and the like.

  1,3-diol has two asymmetric carbons and can produce a diastereomer from its positional relationship, but is synthesized as a mixture of a threo type and an erythro type by a known production method. For example, Non-Patent Document 1 discloses a method in which a hydroxyalkanone is synthesized and reduced with lithium aluminum hydride to obtain a mixture of threo and erythro, and then fractionated by column purification. . Moreover, when the foam eliminating ability was evaluated using 1,3-diols having different steric structures, it was reported that the threo type was superior to the erythro type. However, there is a problem that enormous costs are required for industrial application of column generation.

  As means for eliminating the purification step, Non-Patent Document 2 discloses a method for selectively obtaining an erythro type by coordinating a boron compound to β-hydroxyketone and reducing it. However, this method has a problem that, in addition to using a boron-based compound that is harmful to the environment, a step of removing the boron-based compound during purification is required. In addition, it is theoretically difficult to selectively synthesize only the threo form by this method.

Yuka Chemical, 31, 1014-1020 (1982) Tetrahedron, 40, 2233-2238 (1984)

  An object of the present invention is to provide a method capable of producing a threo-type long-chain 1,3-alkanediol at a low cost and in a high yield.

  As a result of intensive studies, the present inventors have recrystallized using a mixed solvent having a volume ratio of hexane / ethyl acetate = 90/10 to 60/40, so that the amount of use is less than when a single solvent is used. The inventors have found that threo-type long-chain 1,3-alkanediol can be produced in a high yield with a solvent amount, and the present invention has been completed.

That is, the present invention relates to 1,3-alkanediol having 15 to 25 carbon atoms and a threo: erythro ratio of 30/70 to 70/30 to a volume ratio of hexane / ethyl acetate of 90/10 to 60/40. The threo-type long-chain 1,3-alkanediol represented by the formula (1) is characterized by recrystallization using a mixed solvent of
(Wherein R ¹ and R ² represent an alkyl group or an alkenyl group having 5 to 17 carbon atoms.)
The present invention is also a threo-type long-chain 1,3-alkanediol obtained by the above production method and having a threo-type ratio of 99% or more.

  According to the present invention, a threo-type long-chain 1,3-alkanediol, which is an important compound as a raw material for biologically active substances such as general-purpose chemicals, monomers for functional polymers and intermediates for active pharmaceutical and agricultural chemicals, The yield is low and it can be produced industrially advantageously.

  Hereinafter, although the preferable form for implementing this invention is demonstrated in detail, the scope of the present invention is not limited to these forms.

The long-chain 1,3-alkanediol composed of a mixture of threo type and erythro type used in the production method of the present invention can be synthesized by known methods described in Non-Patent Documents 1 and 2. That is, examples include a method of synthesizing a long-chain 1,3-alkanediol by aldol condensation of an aldehyde and a ketone under a basic catalyst to obtain a keto alcohol, and reducing the carbonyl group with an appropriate reducing agent. . Aldehydes and ketones have an alkyl or alkenyl group having 5 to 17 carbon atoms. The alkyl group or alkenyl group constitutes R ¹ and R ² in a long-chain 1,3-alkanediol having a total carbon number of 15 to 25 shown in Formula (1). The 1,3-alkanediol may have an unsaturated bond, and R ¹ and R ² may be branched. From the viewpoint of the effect of the present invention, R ¹ and R ² are preferably alkyl groups, and are preferably linear.

  Ketoalcohol reduction methods include sodium borohydride, lithium aluminum hydride, sodium bis (2-methoxyethoxy) aluminum hydride, diisobutylaluminum hydride, borane, borane-tetrahydrofuran complex, borane-dimethylsulfide complex, borane-pyridine. A reduction reaction using a reducing agent such as a complex, or catalytic reduction can be used. When a good yield is ensured and safety is taken into consideration, it is preferable to use sodium bis (2-methoxyethoxy) aluminum hydride having reactivity equivalent to aluminum hydride and low pyrophoricity.

  The amount of the reducing agent used is preferably 1.0 to 10.0 equivalents relative to the keto alcohol, and 1.1 to 2.0 equivalents from the viewpoint of reactivity and atomic efficiency. Is preferred.

  The temperature condition of the reduction reaction may be in a range that does not extremely impair the activity of the reactant and the selectivity of the target compound, but a range of −40 ° C. to 140 ° C. is preferable. In the case of −40 ° C. or lower, from the viewpoint of cost, and in the case of 140 ° C. or higher, the substrate keto alcohol starts to decompose, which is not preferable from the viewpoint of substrate stability.

  As a solvent used in the reduction reaction, a commercially available reagent can be used as long as it does not have an ester, a carbonyl group, a nitro group or the like. When a highly reducing reagent such as lithium aluminum hydride or sodium bis (2-methoxyethoxy) aluminum hydride is used, it is preferable not to use an alcohol solvent because it reacts with the solvent itself.

  After completion of the long chain diol synthesis step, a mixture of a threo type and an erythro type of long chain diol can be obtained by general quenching (neutralization), extraction, and washing, and then threo type long chain 1,3 by recrystallization. -Alkanediol can be isolated and purified inexpensively and easily.

  As the solvent used for recrystallization of the threo-type long-chain 1,3-alkanediol of the present invention, a mixed solvent of ethyl acetate and hexane is used from the viewpoint of solubility of the diol and distillation of the solvent after purification.

  Recrystallization of the threo-type long chain 1,3-alkanediol of the present invention can be performed by a commonly used technique such as a crystallization method by temperature change or solvent composition change. It is preferable to use a technique utilizing temperature change from the viewpoint of yield.

  The temperature at which the threo-type long-chain 1,3-alkanediol of the present invention is recrystallized can be from 0 ° C. to the boiling point of the solvent used. A temperature of about ° C is preferred.

  The amount of solvent used for recrystallization of the threo-type long-chain 1,3-alkanediol of the present invention can be reduced to 1.5 times the limit amount at which diol can be dissolved at the maximum temperature at which recrystallization is performed. . Further reduction of the amount of solvent is not preferable because it causes a decrease in purity.

  For the washing of the crystals performed during the recrystallization of the threo-type long-chain 1,3-alkanediol of the present invention, it is possible to use a generally used solvent, but it is preferable to use a solvent having low diol solubility. Preferably, it is more preferable to use at a low temperature. The number of crystal washings is preferably about 3 from the viewpoints of purity and yield, and the amount of solvent used for each washing is preferably about twice the weight of the diol in terms of cost.

The three-dimensional structure of the threo-type long-chain 1,3-alkanediol of the present invention can be assigned by ¹ H-NMR analysis because the chemical shifts of alcohol hydrogen and α-position hydrogen of alcohol are different. Specifically, the erythro type easily forms an intramolecular hydrogen bond, so alcohol hydrogen shifts in a low magnetic field, whereas the threo type hardly forms an intramolecular hydrogen bond, so the alcohol hydrogen is high, contrary to the erythro type. Magnetic field shift.

As the solvent used for the ¹ H-NMR analysis of the threo-type long-chain 1,3-alkanediol of the present invention, a general heavy solvent may be used as long as it dissolves the diol and has no peak at 4 ppm or less. It is preferable to use deuterated chloroform which has good solubility and is inexpensive.

EXAMPLES The present invention will be specifically described below with reference to examples and comparative examples, but the present invention is not limited to these.
(NMR conditions)
The measurement of ¹ H-NMR used in Examples and Comparative Examples was performed using Lambda 500 manufactured by JEOL. The measurement was performed under the conditions of a frequency of 500 MHz and a total number of integrations of 8 by putting 5 to 10 mg of sample in an NMR tube and dissolving it in a heavy solvent of about 0.5 to 0.8 ml. ^As the solvent used for the ¹ H-NMR measurement, chloroform-D (D, 99.8%, +0.05 v / v TMS, containing silver foil) purchased from Wako Pure Chemical Industries was used as it was without purification.

[Example 1]
<Hexane / Ethyl acetate 75/25>
7.4 g of 9,11-eicosanediol having a threo ratio of 58.7% was placed in a 500 ml round bottom flask, and 34.5 ml of a mixed solvent of hexane / ethyl acetate = 75/25 (9,11-eicosanediol at 50 ° C. Was added to the solution, and the mixture was heated to 50 ° C. in a water bath to be completely dissolved. The concentration of the saturated solution was diluted 1.5 times (total amount 51 ml), and the temperature was gradually lowered to 30 ° C. in one hour to precipitate white crystals. Thereafter, the mixture was stirred for 3 hours at room temperature, filtered with suction, washed out with 60 ml of 5 ° C. hexane, and washed with crystals. The obtained crystals were vacuum-dried for 8 hours to obtain 4.2 g (yield 56.7%) of white crystals. ^{From the 1} H-NMR measurement result, it was identified that the obtained white crystals were 9,11-eicosanediol, and it was confirmed that the threo ratio was> 99%. Since a threo-type 9,11-eicosanediol having a yield of 56.7% and a purity> 99% was obtained from a raw material having a threo ratio of 58.7%, the threo form recovery rate was 95.7%.
^<1 H-NMR measurement results> (threo)
¹ H-NMR (500 MHz, CDCl ₃ ): δ 0.88 (dt, 6H), 1.27-1.65 (m, 32H), 1.60 (dd, 2H), 2.32 (brs, 2H), 3.92-3.94 (m, 2H) .
^<1 H-NMR measurement results> (erythro)
¹ H-NMR (500 MHz, CDCl ₃ ): δ 0.88 (dt, 6H), 1.27-1.65 (m, 32H), 1.60 (dd, 2H), 3.04 (brs, 2H), 3.83-3.84 (m, 2H) .

[Comparative Example 1] <Hexane / Ethyl acetate = 100/0>
Recrystallization, washing, and drying were performed in the same manner as in Example 1 except that 180 ml of 9,11-eicosanediol was completely dissolved at 50 ° C. A white solid was obtained in a yield of 3.6 g (yield 48.0%), the threo ratio was> 99%, and the threo form recovery rate was 81.8%.

[Comparative Example 2] <Hexane / Ethyl acetate = 50/50>
Recrystallization, washing, and drying were performed in the same manner as in Example 1 except that 9,11-eicosanediol was completely dissolved at 50 ° C. using 22.6 ml of a mixed solvent of hexane / ethyl acetate = 50/50. It was. A white solid was obtained with a yield of 4.32 g (yield 58.4%), the threo ratio was 90%, and the threo form recovery rate was 89.5%.

[Comparative Example 3] <Hexane / Ethyl acetate = 25/75>
Recrystallization, washing, and drying were performed in the same manner as in Example 1 except that 9,11-eicosanediol was completely dissolved at 50 ° C. using 24.8 ml of a mixed solvent of hexane / ethyl acetate = 25/75. It was. A white solid was obtained with a yield of 4.20 g (yield 56.8%), the threo ratio was 93%, and the threo form recovery rate was 90.0%.

  The results of Example 1 and Comparative Examples 1 to 3 are shown in Table 1. From the results shown in Table 1, in the method for producing a threo-type long-chain 1,3-alkanediol of the present invention, a threo-type having a purity of 99% or more can be produced with good yield and low cost.

  From the above results, the method for producing the threo-type long-chain 1,3-alkanediol of the present invention has a carbon number of 15 to 15 in a highly selective and inexpensive manner compared with the production methods of Non-Patent Document 1, Patent Documents 1 and 2. 25 threo-type long chain 1,3-alkanediols can be produced.

  According to the present invention, threo-type long-chain 1,3-alkanediol, which is an important compound as a raw material for biologically active substances such as general-purpose chemicals, monomers for functional polymers and intermediates for active pharmaceuticals and agricultural chemicals, is obtained in high yield. In addition, it is inexpensive and can be produced industrially advantageously.

Claims (2)

From 1,3-alkanediol having 15 to 25 carbon atoms and a threo: erythro ratio of 30/70 to 70/30, using a mixed solvent having a volume ratio of hexane / ethyl acetate of 90/10 to 60/40 A method for producing a threo-type long-chain 1,3-alkanediol represented by the formula (1), which comprises recrystallization.
(Wherein R ¹ and R ² represent an alkyl group or an alkenyl group having 5 to 17 carbon atoms.)   A threo-type long-chain 1,3-alkanediol obtained by the production method according to claim 1 and having a threo-type ratio of 99% or more.