JPH1149719A - Omega-phenyl-(omega, omega-2)-dieno-fatty acids, their production and production of omega-phenyl straight-chain fatty acids - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new fatty acids useful as various synthetic raw materials or intermediates. SOLUTION: The fatty acids are represented by the formula Ph-CH=CH-CH =CH-(CH2 )n -CO<2> H [Ph is phenyl; (n) is an integer of 2-5], e.g. 7-phenyl-4,6- heptadienoic acid. The fatty acids are obtained by reacting (A) cinnamaldehyde with (B) a Witting reagent represented by the formula BrPh3 P(CH2 )n+1 CO2 H (e.g. 3-carboxypropyltriphenyphosphonium bromide) in an amount of about 0.5-3 mol based on 1 mol component (A) in the presence of (C) an alkali in an amount of about 2-3 mol based on 1 mol component B (sodium hydride or potassium t-butoxide) in (D) an organic solvent (diethyl ether or the like) in an amount of about 3-20 times based on the component B at about -70 to +30 deg.C for 1-24 hr.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to .omega.-phenyl-(. Omega.,. Omega.-2) -dieno fatty acids useful as various synthetic raw materials or intermediates which have not been described in the prior art and to a process for producing the same. Furthermore, the present invention relates to a method for producing ω-phenyl linear fatty acids useful as various synthetic raw materials or intermediates via ω-phenyl- (ω, ω-2) -dieno fatty acids.

[0002]

2. Description of the Related Art Conventionally, the Wittig reaction is well known (Org. Reac.
tion, Vol.14). However, a Wittig reagent represented by cinnamaldehyde and a general formula (II) BrPh ₃ P (CH ₂ ) _{n + 1} CO ₂ H (wherein Ph represents a phenyl group and n represents an integer of 2 to 5) With Wittig reagent II). In the present invention, a novel compound represented by the general formula (I) Ph-CH = CH-CH
= CH- and _{(CH 2) n -CO 2 H} ( wherein Ph is a phenyl radical, n is 2-5
Ω-phenyl- (ω, ω-
It has been found that 2) -dieno fatty acids can be synthesized.
In addition, the above compound is easily used as an intermediate to easily prepare a compound of the general formula (II
I) It is possible to lead to ω-phenyl linear fatty acids represented by Ph- (CH ₂ ) _{n + 4} —CO ₂ H (where Ph represents a phenyl group and n represents an integer of 2 to 5). is there. Furthermore, the present invention provides an inexpensive and readily available cinnamaldehyde and Wittig reagent II.
This is a very industrially advantageous method because it is used as a raw material.

Accordingly, an object of the present invention is to provide a novel compound ω-phenyl- (ω, ω-) using cinnamaldehyde and Wittig reagent II which are inexpensive and easily available.
2) -Dieno fatty acids are synthesized, and the above compounds are used as intermediates to lead to ω-phenyl linear fatty acids.

[0004]

The present invention provides a compound represented by the general formula (I):
(A wherein Ph is a phenyl group, n represents an integer of 2~5) Ph-CH = CH- CH = CH- (CH 2) n -CO 2 H represented by .omega.-phenyl - (omega, .omega. 2) -dieno fatty acids, cinnamaldehyde and the general formula (II) BrPh ₃ P (CH ₂ ) _{n + 1} CO ₂ H (where P
h is a phenyl group, n is an integer of 2 to 5), and is reacted with a Wittig reagent in an organic solvent in the presence of an alkali in an organic solvent, wherein the ω-phenyl- (ω, ω-
2) A process for producing -dieno fatty acids, and reacting the ω-phenyl- (ω, ω-2) -dieno fatty acids with hydrogen in the presence of a metal catalyst, the general formula (II)
I) This is a method for producing ω-phenyl linear fatty acids represented by Ph- (CH ₂ ) _{n + 4-} CO ₂ H (wherein Ph represents a phenyl group and n represents an integer of 2 to 5).

The production method of the present invention is represented by the following reaction formula. Ph-CH = CH-CHO + BrPh ₃ P (CH ₂ ) _{n + 1} CO ₂ H → Ph-CH = CH-C
H = CH- (CH ₂ ) _n -CO ₂ H → Ph- (CH ₂ ) _{n + 4-} CO ₂ H

[0006] Cinnamaldehyde, which is the starting material of the present invention, can be easily and inexpensively obtained as a perfume raw material or various synthetic raw materials. The other starting material, the Wittig reagent (II), is a known compound and is easily available industrially. In addition, literature (J. Org. Chem., 42 , 278
3 (1977)), the general formula Br (CH ₂ ) _{n + 1} CO ₂ H
(Where n represents an integer of 2 to 5), and can be easily produced by reacting an ω-bromo linear fatty acid represented by the following formula with triphenylphosphine represented by the chemical formula Ph ₃ P.

Specific examples of the Wittig reagent include 3-carboxypropyltriphenylphosphonium bromide,
4-carboxybutyltriphenylphosphonium bromide, 5-carboxypentyltriphenylphosphonium bromide, and 6-carboxyhexyltriphenylphosphonium bromide. The amount of the Wittig reagent used is about 0.5 mol to 1 mol of cinnamaldehyde.
About 3 moles, more preferably in the range of about 0.5 mole to about 1 mole can be exemplified.

Specific examples of the alkali include sodium hydride, potassium t-butoxide, n-butyllithium,
Phenyllithium and the like can be mentioned, but it is preferable to use sodium hydride and potassium t-butoxide which are easy to handle. The amount of the alkali used is in the range of about 2 mol to about 3 mol per 1 mol of the Wittig reagent. When the amount of the alkali used is less than the lower limit, the reaction does not proceed sufficiently. On the other hand, if the ratio exceeds the upper limit, the proportion of by-products increases, and neither is preferred.

The organic solvent used in the above reaction includes, for example, diethyl ether, tetrahydrofuran, dimethylformamide, dimethylsulfoxide, dimethylacetamide and the like. The amount of the organic solvent used is not particularly limited, but a range of about 3 to about 20 times the weight of the Wittig reagent can be more preferably exemplified.

[0010] The reaction temperature is, for example, about -70 ° C to about 30 ° C.
° C, more preferably in the range of about 0 ° C to about 10 ° C, and the reaction time is about 1 hour to about 24 hours, more preferably about 1 hour.
Hours to about 4 hours can be exemplified.

After completion of the reaction, the reaction is stopped by adding ice water, and after extracting the non-acidic portion with an organic solvent, the remaining aqueous layer is neutralized with an acid. Further, after extraction with an organic solvent, washing with water, drying and concentration of the organic layer according to a conventional method, the ω-phenyl- (ω, ω-2) -dieno fatty acid is purified by means such as silica gel column chromatography. Can be obtained.

Specific examples of ω-phenyl- (ω, ω-2) -dieno fatty acids which can be obtained as described above include 7-phenyl-4,6-heptadienoic acid, 8-phenyl-5, 7-octadienoic acid, 9-phenyl-6,8
-Nonadienoic acid and 10-phenyl-7,9-decadienoic acid. The stereoselectivity of the above compound is ¹
From H-NMR analysis, the double bond at the ω-position is the same trans as that of the starting material cinnamaldehyde. The double bond at the ω-2 position is a mixture of trans and cis, and the ratio can be exemplified in the range of trans / cis = 50/50 to 25/75.

Next, the reduction step will be described. Examples of the metal catalyst used for reduction of the ω-phenyl- (ω, ω-2) -dieno fatty acids represented by the general formula (I) include 5% palladium carbon, Raney nickel, nickel boride, iridium black and the like. , But more preferably 5% palladium carbon. The amount of the catalyst used is the same as that of the ω-phenyl- (ω, ω-2).
-The amount may be, for example, in the range of about 0.01 to about 1 time by weight, more preferably about 0.02 to about 0.1 time by weight based on the dieno fatty acids.

The organic solvent used in the above reaction includes, for example, methanol, ethanol, ethyl acetate, acetic acid, tetrahydrofuran, benzene, hexane and the like. Although there is no particular limitation on the amount of these organic solvents used, a preferred range is about 3 to about 10 times the weight of the ω-phenyl- (ω, ω-2) -dieno fatty acids. Can be.

The reaction temperature ranges, for example, from about 0 ° C to about 50 ° C, more preferably from about 15 ° C to about 30 ° C, and the reaction time ranges from about 1 hour to about 12 hours, more preferably from about 1 hour to about 1 hour. About 6 hours can be exemplified. Further, the hydrogen pressure can be adjusted under the atmospheric pressure condition and the pressurized condition of 10 kg / cm ² or less.

After completion of the reaction, the catalyst is removed by filtration, and the filtrate is concentrated and purified by means such as silica gel column chromatography to obtain ω-phenyl linear fatty acids represented by the general formula (III). be able to.

Specific examples of the ω-phenyl linear fatty acids that can be obtained as described above include 7-phenylheptanoic acid, 8-phenyloctanoic acid, 9-phenylnonanoic acid, and 10-phenyldecanoic acid. Can be

[0018]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the present invention is limited thereto.

Example 1 Synthesis of 9-phenyl-6,8-nonadienic acid 4.95 g of potassium t-butoxide (4.
4.1 mmol) and 50 g of tetrahydrofuran, and cooled with ice water. Under cooling, 10.0 g (21.0 g) of 5-carboxypentyltriphenylphosphonium bromide
Mmol) and stirred for 1 hour. Subsequently, 3.33 g (25.2 mmol) of cinnamaldehyde was added dropwise under cooling, and the mixture was stirred for 2 hours. After the reaction is completed, add ice water 100
g, and the non-acidic portion was extracted four times with 50 g of toluene.
The remaining aqueous layer was neutralized with hydrochloric acid, extracted with 50 g of toluene, washed three times with 50 g of water, dried over anhydrous sodium sulfate and concentrated to dryness to obtain a pale yellow solid. The obtained solid was purified using a silica gel column using hexane / ethyl acetate = 5/1 (volume ratio) as a developing solvent, and 3.00 g (13.0 mmol, yield based on Wittig reagent of 62%) of a white solid was obtained. I got

The results of analyzing this white solid are as follows. (1) m. p. 54 to 58 ° C (2) IR (KBr, cm ^-1 ) 3620-250
0, 3030, 2940, 1710, 990, 690 (3) MS (EI) 230 (M ⁺ ) (4) ¹ H-NMR (CDCl ₃ , δ (ppm)) 1.4
7 to 1.55 (m), 1.63 to 1.76 (m), 2.
18 (dt, trans body 5 of CH _2), 2.27~2.
4. 42 (m), 5.52 (dt, 6-position CH in cis form);
80 (dt, 6-position CH in trans form), 6.13-6.2
5 (m, 8-position CH), 6.45 (d, trans-form 9-position C
H), 6.53 (d, cis-form 9-position CH), 6.74 (d
d, trans 7-position CH), 7.05 (dd, cis 7
CH), 7.19 to 7.43 (m) The above trans and cis isomers represent a steric double bond at the 6-position. From the above analysis values, it was confirmed that the product was 9-phenyl-6,8-nonadienoic acid. For the steric double bond,
^{According to 1} H-NMR analysis, the double bond at the 8-position was trans,
The double bond at position 6 was a mixture of trans / cis = 35/65.

Example 2 Synthesis of 9-phenylnonanoic acid 10.0 g of 9-phenyl-6,8-nonadienoic acid (4
3.4 mmol), 5% palladium carbon 0.500
g and 50 g of ethanol were charged and degassed under reduced pressure, and then the inside of the system was replaced with hydrogen gas. At normal pressure and room temperature with stirring 4
Allowed to react for hours. After completion of the reaction, the catalyst was removed by filtration, and the filtrate was concentrated to dryness to obtain a slightly yellow solid. The obtained solid was purified using a silica gel column using hexane / ethyl acetate = 5/1 (volume ratio) as a developing solvent, and 7.83.
g (33.4 mmol, 77% yield) of a white solid was obtained. M.p. of this white solid. p. , IR, MS, ¹ H-NM
R was analyzed and confirmed to be 9-phenylnonanoic acid.

[0022]

According to the present invention, a novel compound ω-phenyl- (ω, ω-
2) -dieno fatty acids can be provided. Further, the production method of the present invention uses cinnamaldehyde and Wittig reagent II, which are inexpensive and readily available, as raw materials, and thus is a very industrially advantageous method. Further, using the novel compound as a raw material, ω is easily used as various synthetic raw materials or intermediates.
-Can produce phenyl straight chain fatty acids.

Claims (3)

[Claims] 1. A compound of the general formula (I) Ph-CH = CH-CH = CH- (CH ₂ ) _n -CO ₂
H (wherein Ph represents a phenyl group, and n represents an integer of 2 to 5)
Ω-phenyl- (ω, ω-2) -dieno fatty acids represented by the formula: 2. Cinnamaldehyde and BrP of the general formula (II)
h ₃ P (CH ₂ ) _{n + 1} CO ₂ H (wherein Ph is a phenyl group, and n is 2 to 5
2. The process for producing ω-phenyl- (ω, ω-2) -dieno fatty acids according to claim 1, wherein the reaction is carried out in an organic solvent in the presence of an alkali. . 3. The ω-phenyl- (ω, ω-) according to claim 1.
2) - Jieno fatty acids the presence of a metal catalyst, and wherein the reaction with hydrogen, the formula _{(III) Ph- (CH 2)} n + 4 -C
A process for producing ω-phenyl linear fatty acids represented by O ₂ H (wherein Ph represents a phenyl group and n represents an integer of 2 to 5).