JPS63198645A - Production of brassylic acid lower alkyl ester - Google Patents

Abstract

PURPOSE:To advantageously obtain the titled substance which is a synthetic intermediate of musk or perfume substance while safely recovering a generation gas, etc., by subjecting a halogenated brassylic acid dilower alkyl ester of a raw material which is readily available and inexpensive to hydrocracking with Raney nickel in the presence of a tert. amine. CONSTITUTION:Hydrocracking reaction is carried out by using a halogenated brassylic acid di-lower alkyl ester as a raw material in the presence of Raney nickel and a tert. amine (preferably tri-n-butyl amine) in a solvent such as methanol, isobutanol, etc., to provide the aimed compound. The reaction is carried out using an autoclave at hydrogen pressure of 1-20kg/cm<2>, preferably 5-15kg/cm<2> and about 50-100 deg.C, preferably 70-80 deg.C. A 2-halogenated brassylic acid di-lower alkyl ester which is a raw material compound is synthesized from an undecylenic acid ester obtained by thermal decomposition of castor oil and monohalogenated acetic ester.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing brassylic acid di-lower alkyl esters useful as intermediates in the synthesis of musk fragrance substances.

[Conventional technology]

The brassylic acid di-lower alkyl ester of the present invention has the general formula (
1) (In the formula, R+ and Rg represent the same or different lower alkyl groups.) It is an important intermediate in the synthesis of musk fragrance substances, that is, brassylic acid cyclic ethylene ester. The most common method for producing brassylic acid di-lower alkyl esters has traditionally been a method of esterifying brassylic acid obtained by ozone oxidation of erucic acid present in the hydrolyzate of rapeseed oil (S, C, Bha-ttacharyya et al. Ind
ian J, cheIl, 4, (12), 5
24. (1966)), a method for synthesizing adipic acid monoester and adipic acid monoester by Kolbe reaction (JP-A-57-198287), a method for reacting malonic acid with monohalogenated decanoic acid ester (Dudinov,
A, A, et al Izv.

Akad, Nauksssr, Ser Khim, 19
74. (6), 1421),) A method is known in which lysocan is esterified by producing a dibasic acid using a microorganism (Japanese Patent Laid-Open No. 57-206394).

However, with this conventional manufacturing method, it has become difficult to obtain raw materials, and the price of raw materials has been rising, so there has been a strong desire for a synthetic method using cheaper raw materials.

[Problem that the invention seeks to solve]

The present invention was newly created in view of the above circumstances, and its main objective is to carry out a hydrogenolysis reaction of halogenated brassylic acid di-lower alkyl ester in the presence of a tertiary amine, which is advantageous on an industrial scale. To provide a method for producing brassylic acid di-lower alkyl ester.

[Means for solving problems]

In order to solve the above problems, the present invention involves carrying out a hydrogenolysis reaction on a halogenated brassylic acid di-lower alkyl ester in the presence of Raney nickel and a tertiary amine, and converting the generated hydrogen halide into a salt of a tertiary amine. relates to the synthesis of brassylic acid di-lower alkyl esters by hydrogenating the hydrogenation catalyst Raney nickel without inactivation.

The present inventors conducted intensive research on hydrogenolysis reactions using various bases and hydrogenation catalysts using halogenated brassylic acid di-lower alkyl ester as a starting material, and found that nickel, unlike platinum and palladium, does not react with hydrogen halides. It becomes a catalyst poison (A, R, Pinder, 5ynt
Hesis 4251980) eNevertheless, by skillfully using a tertiary amine base, hydrogen halide, which is a catalyst poison, can be removed as a salt, thereby increasing the reaction yield without inactivating Raney nickel, the hydrogenation catalyst. They found that the process progresses well and have completed the present invention.

One of the raw materials used in the present invention, 2-halogenated brassylic acid di-lower alkyl ester, is obtained from an inexpensive undecylenic acid ester obtained by thermal decomposition of castor oil and a monohalogenated acetic acid ester using di-tert-butyl peroxide as a catalyst. The radical addition reaction produces the following reaction formula [1]
It is synthesized as follows.

(D, LEFORT Bull, Soc, Chim,
Fr,, (11) 4613. (1968)) 1 → R
+0CCH(CHz)+. coRz
(1) (wherein, X represents CI or Br, RI+
Rz represents the same lower alkyl group as in the general formula (1). ) On the other hand, in the synthesis of tetrahalogenated brassylic acid di-lower alkyl ester, a solution of undecylenic acid ester in a hydrocarbon solvent (for example, n-hebutane, benzene, or toluene is preferable) and a monohalogenoacetic acid ester are placed in an autoclave. After sufficiently purging with nitrogen, a ruthenium-phosphine complex is added, and the mixture is heated and stirred to react.

In addition, the amount of preparation is 18 to 24 monohalogenoacetate per 10mM (mmol) of undecylenate.
mM, ruthenium-phosphine complex 0.005-0.1
Preferably, it is used in a ratio of mM.

Further, the reaction temperature is desirably within the range of 110°C to 180°C from the viewpoint of promoting the reaction and preventing side reactions.

Here, the reaction time usually requires several hours to about 20 hours.

The ruthenium-phosphine complexes used as catalysts in the present invention are those in which tertiary phosphine is coordinated with ruthenium, such as those listed below.

RuHz (PPh3) 4 (PPb3 represents triphenylphosphine, the same applies hereinafter) RuHCl (PPha) 3 RuC1z (PPhz) ! RuzClt (PTO13) HtffNCPToli represents tritolylphosphine, I!t3N represents triethylamine, the following Same] Ru2C14(PNaphi)4EtJ(PNaphs
represents trinaphthylphosphine, the same applies hereinafter] RuzCl4 (dppb) zEtsN (dppb represents 1,4-bis (diphenylphosphino)butane, the same applies hereinafter)] (RuzCl, : + (CI87P),) CI These complexes All of these are known substances, for example, in literature, New Experimental Chemistry Course, 12. P157-P165 (1976, Maruzen), or Preten op the Chemical Society op Japan (Bull, Chew.

Soc, Jan) 57.897 (1984).

As described above, undecylenic acid ester and monohalogenoacetic acid ester are reacted in the presence of a ruthenium-phosphine complex to produce tetrahalogenated brassylic acid di-lower alkyl ester.

In the present invention, brassylic acid di-lower alkyl ester is synthesized as follows using the obtained halogenated brassylic acid di-lower alkyl ester as a raw material.

That is, about 1 mole of halogenated brassylic acid di-lower alkyl ester and about 1.5 to 3.5 moles of a tertiary amine such as tri-n-butylamine are added to an autoclave, and an alcohol such as methanol, ethanol, or isopropanol is added. About 5 to 10 moles of Raney nickel are added thereto and dissolved, and about 0.01 to 0.1 moles of Raney nickel are added thereto to raise the hydrogen pressure to 1 to 20 kg/cll, preferably 5 to 15
kg/- about 50-100℃, preferably 70-80℃
The hydrogenolysis reaction is carried out at a temperature of 2 to 5 hours.

After hydrogen absorption is completed, the reaction is continued for 1 to 2 hours to complete the reaction. The reaction mixture is filtered to remove the catalyst and the solvent is recovered under reduced pressure. To the residue, add an organic solvent that separates water such as benzene, toluene, xylene, n-hexane, etc. and dissolve it. Add sulfuric acid and stir to transfer the tertiary amine to the aqueous layer. After separating the aqueous layer, add the organic solvent layer. After neutralization and washing with an aqueous solution of sodium carbonate and aqueous sodium carbonate solution, the organic solvent layer is separated.

The organic solvent layer was distilled off and recovered under reduced pressure.
Brassylic acid di-lower alkyl ester is obtained. For the tertiary amine used in the reaction, an aqueous solution of caustic soda is added to the amine extraction aqueous layer, stirred at about 20 to 60°C for 5 minutes, and then allowed to stand. The aqueous layer is separated and removed to recover the tertiary amine.

Tertiary amines used here include, for example, triethylamine, tri-n-butylamine, triisopropylamine,
Examples include tri-n-hexylamine, tri-n-octylamine, tri-2-ethylhexylamine, dimethylbutylamine, dioctylmethylamine, dibutyl-2-ethylhexylamine, N-ethylpiperidine, N-ethylpyrrolidine, and N-ethylpipecoline. but preferably tri-n-butylamine, triisopropylamine, dibutyl-2-ethylhexylamine, tri-n-butylamine,
Hexylamine.

Commercially available Raney nickel used in the present invention is sufficient to achieve the purpose.

The yield of brassylic acid di-lower alkyl ester obtained here is almost quantitative and is the best, and it is purified by distillation or column chromatography if necessary.

For example, brassylic acid di-lower alkyl ester can be prepared by a known method shown by the following reaction formula (2) (for example, Japanese Patent Publication No. 46-3
No. 7584), a polyester can be obtained by esterification reaction or transesterification with ethylene glycol, and further thermal depolymerization can be carried out to obtain a monomeric brassylic acid cyclic ethylene ester.

ORZ \Co-C)It (wherein RI+Rz is the same as defined above) This brassylic acid cyclic ethylene ester is extremely important as one of the musk fragrance substances.

〔Example〕

Next, the present invention will be explained in detail using reference examples and examples.

Reference Example 1 Synthesis of dimethyl 2-chlorobrassylate 1.047 kg of methyl monochloroacetate was charged into a 2 rrr reaction vessel, heated to start refluxing, and then 147.5 kg of methyl undecylenate (purity 97.6%) and methyl monochloroacetate were added. A mixed solution of 147.5 k+r and 17.7 kg of di-tert-butyl peroxide is added dropwise over about 15 hours.

After the dropwise addition was completed, the mixture was stirred for an additional 3 hours under the same conditions and then allowed to ripen. After the reaction is completed, the strained section is cooled to 70° C., and excess methyl monochloroacetate is subsequently recovered under reduced pressure.

A residue of 238 kg of dimethyl 2-chlorobrassylate is obtained. 150 g of dimethyl 2-chlorobrassylate with a theoretical yield of 72.2% and a purity of 67.6% was distilled under reduced pressure to obtain a boiling point of 165.
106 g of a 11 g fraction of ~168° C./1 mm are obtained.

This substance was confirmed to be dimethyl 2-chlorobrassylate with a purity of 95% by analysis using measurements such as IR spectrum, NMR spectrum, and mass spectrum.

IR spectrum: 1720cm-'NMR:
3.4PPM S, 6) 1 mass spectrum: 306 (
M”) Reference Example 2 Synthesis of dimethyl 4-chlorobrassylate 100% of methyl undecylenate was placed in a 500% autoclave.
(50.5mM), toluene 20mZ, monochloromethyl acetate LL, 7g (108mM), and the autoclave was sufficiently purged with nitrogen gas, and RuCl
z (PPh, l) 397wg (0.1mM) and toluene 5rBl were added.

The reaction mixture was then reacted at 150° C. for 15 hours with stirring, and the resulting reaction solution was washed with 5% aqueous sodium carbonate.

Next, after distilling off the solvent, vacuum distillation was performed to obtain a boiling point of 165
℃~170℃/1 m+*Hg distilled off was collected to obtain 7.8 g of dimethyl 4-chlorobrasylate with a purity of about 85% (yield 76%).

This was then purified by column chromatography,
Dimethyl 4-chlorobrassylate with a purity of nearly 100% was obtained.

Reference Example 3 Synthesis of diethyl 2-chlorobrassylate Add +r to 2n? of monochloroethyl acetate 1182? After heating and refluxing, 158ktr of ethyl undecylenate (purity 97.6%) and 16ktr of ethyl monochloroacetate were added to a reaction vessel.
6.5kg and G-Lert-Butyl Peroxide 19
kg of the mixed solution was added dropwise over about 15 hours. After the completion of the dropwise addition, stirring was continued for an additional 3 hours under the following conditions to complete the reaction. After the completion of the reaction, the trough was cooled to 70°C, and then the excess monochlore was removed under reduced pressure. Collect ethyl acetate.

At this time, diethyl 2-chlorobrassylate is obtained as a residual oil in the pot. Yield: 260 kg, purity: 67.4%, theoretical yield: 72.0%. Part of this residual oil is distilled under reduced pressure,
A fraction with a boiling point of 180 to 185°C and 10.5 nusHg was collected, and gas chromatography, GS-Mass spectrum, NMR spectrum, and IR spectrum were measured.
This product was confirmed to be diethyl 2-chlorobrasylate with a purity of 95%.

IR spectrum: 1720C! l-'NMR#: (3,8PPM, q, 411)
(1,2PPM, t, 6H) Mass spectrum: 3
34 (M+) Example 1 17! Purity 6 obtained in Reference Example 1 in the autoclave of
175 g of 7.6% dimethyl 2-chlorobrassylate (0
, 386 mol) and 159 g of tri-n-butylamine (
0.86 mol) methanol (233 g) and 3.5 g of Raney nickel catalyst (manufactured by Yoken Fine Chemicals) were taken, and hydrogenolysis was carried out at 70°C under a hydrogen pressure of 10 kg/-. Although absorption of hydrogen is completed in 6 hours, the reaction is continued for an additional 2 hours under the same conditions to complete the reaction. After filtering the catalyst from the reaction mixture, 228.9 g of methanol (containing 4.3 g of tri-n-butylamine) is recovered under reduced pressure. The methanol recovery rate was 96.4% of the theoretical amount. This methanol can be recycled as is. Residual oil after methanol recovery 33
After dissolving 220 g of toluene in 7.5 g, 450 g of 7% dilute sulfuric acid (0.32 M) was added and stirred, and tri-butylamine was extracted into the aqueous layer. After separating the aqueous layer, add the same amount of 2% sodium carbonate aqueous solution, 2% sodium bicarbonate aqueous solution, and 2.5% saline solution to the toluene layer and separate the neutralized condensate layer. .

210g of toluene from the toluene layer under reduced pressure (recovery rate 9
5%) recovered and 70.3% pure dimethyl brassylate 1
Obtain 46g. This product was distilled under reduced pressure with a theoretical yield of 98% to obtain 102 g of a fraction with a boiling point of 137 to 140°C/lmmHg.

This substance can be analyzed by gas chromatography, IR spectroscopy,
As a result of analysis such as NMR spectrum and mass spectrum, it was confirmed that the dimethyl brassylate had a purity of 96%.

IR spectrum: 1720cm-'NMR:
3.2PPM S, 6H mass spectrum: 272 (
220 g of a 25% caustic soda aqueous solution was added to 740 g of the aqueous layer extracted from M-tri-n-butylamine, stirred at 50° C. for 5 minutes, and then allowed to stand. The lower aqueous layer is separated and removed, and the oil layer is separated and removed.
151 g of butylamine was recovered. This stuff has a purity of 99
% or more, it does not need to be purified (can be recycled).

Example 2 Dimethyl 4-chlorobrassylate 10 obtained in Reference Example 2
2 g (0.33 mol, purity 100%) was placed in a 11 autoclave, and 74.8 g (0.74 mol) of triethylamine was added to
mole), ethanol 210g, Raney nickel 3.1g
Hydrogenolysis was carried out at 65° C. under a hydrogen pressure of 12 kir/cj. The following treatment was carried out in the same manner as in Example 1 to obtain 90 g of dimethyl brassylate with a purity of 99.5%. The theoretical yield was 98%, and as a result of analysis such as gas chromatography, IR spectrum, NMR spectrum, and mass spectrum, it was confirmed that this substance was dimethyl brassylate with a purity of 96%.

IR spectrum: 1720c1m-'NMR:
3.2PPMS, 6H Mass spectrum: 272 (M”) Example 3 Synthesis of diethylbrasylate by hydrogenolysis reaction 192 g of diethyl 2-chlorobrasylate with a purity of 67.4% obtained in Reference Example 3 and tri-n-butylamine 159
g, methanol 233g and Raney nickel catalyst 3.8g
was placed in an LA autoclave and subjected to hydrogenolysis under the same conditions as in Example 1 to obtain crude diethyl brazilate 16.
1.0 g (purity 70.5%, theoretical yield 98%) was obtained. By distilling this substance under reduced pressure, the boiling point is 150-155℃/
112.3 g of 11 g of l mm fraction was obtained.

This substance can be analyzed by gas chromatography, IR spectroscopy,
Analysis by NMR spectrum, mass spectrum, etc. confirmed that the product was diethyl brassylate with a purity of 96%.

IR spectrum: 1720cm-' NMR〃: (3,8PPM q, 4H) (1,
2PPrut, 6H) Mass spectrum: 300 (M gas chromatography conditions column: silicone 0V-1010, 25φ x 251
11 Temperature: 100-250°C (10°C/m1n) Equipment: Gas chromatography Gc7A (manufactured by Shimadzu Corporation) 111 Nuclear magnetic resonance spectrum (NMR): JNM-G
X400 type (400MHz) (manufactured by JEOL Ltd.) Infrared spectrophotometer (IR): IR-810 (manufactured by JASCO Corporation) [Effects of the invention] According to the present invention, halogenated brassylic acid di-lower alkyl ester It is possible to synthesize di-lower alkyl brasilyl acid ester in high yield from the ester, and the generated hydrogen chloride gas can be captured as a tertiary amine salt, making it safe for labor. Since all tertiary amines can be safely recovered, this method is useful as a method for producing an intermediate for macrocyclic brassylic acid ethylene ester, which is one of the very important musk fragrance substances.

Claims (1)

[Scope of Claims] 1) A method for producing di-lower alkyl brassylate, which comprises carrying out a hydrogenolysis reaction of halogenated di-lower alkyl brassylate in the presence of Raney nickel and a tertiary amine. 2) Halogenated brassylic acid di-lower alkyl ester is 2
or a methyl or ethyl diester of 4-halogenated brassylic acid, the method for producing a di-lower alkyl brassylate ester according to claim 1. 3) The method for producing di-lower alkyl brassylate according to claim 1, wherein the halogen atom of the halogenated di-lower alkyl brassylate is a chlorine atom. 4) The method for producing di-lower alkyl brassylate ester according to claim 1, wherein the tertiary amine is tri-n-butylamine.