JPS60222434A - Preparation of (2e,6e)-3,7,11-trimethyl-2,6,10-dodecatrien-1-al - Google Patents

Abstract

PURPOSE:To prepare the titled compound in high efficiency, by separating (2E, 6E)-farnesyl nitrile from (2Z/E mixture, 6E) or (2Z/E mixture, 6Z/E mixture)- farnesyl nitrile by distillation, reducing the nitrile, and hydrolyzing the product. CONSTITUTION:(2E,6E)-farnesyl nitrile of formula III is separated from the (2Z/E mixture, 6E) or (2Z/E mixture, 6Z/E mixture)-farnesyl nitrile of formula I or formula II by distillation, reduced with diisobutylaluminum hydride or the compound of formula MAlH(OR<3>)3 (M is alkali metal; R<3> is lower alkyl or aryl), and hydrolyzed to obtain the all-trans-farnesal of formula V useful as an intermediate of a remedy for hepatopathy, easily in high purity. The starting substance can be synthesized easily from the (5E) or (5Z/E mixture)-geranylacetone of formula V - formula VI.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention relates to (2E,6E)-3,7,11-)dimethyl-
The present invention relates to a method for producing 2,6,10-dodecatriene-1-al (hereinafter referred to as total transfarnesal).

Total transfarnesal is useful as a synthetic raw material for various pharmaceuticals. For example, a compound represented by the general formula % (1) (where n is an integer of 1 to 4, and R represents a hydrogen atom or a lower alkyl group), which is an active ingredient of a therapeutic agent for liver disorders (JP 1972-
167635) as well as polyprenyl compounds represented by the following formula % formula % ( ) which are active ingredients of anticancer agents or therapeutic agents for skin diseases accompanied by keratinization (see Japanese Patent Application Laid-open No. 167635).
No. 181012, No. 57-106638, No. 57-1
06617 and 57-31615)).

[Conventional technology and its problems]

Until now, no effective method for synthesizing all-transfarnesal was known. For example, (2E, 6E)-3,7,1
1-) Dimethyl-2,6,10-dodecatriene-1-
oxidation of (6E)-3,7°11-trimethyl-6,10-dodecadien-1-yn-3-ol in the presence of a vanadium catalyst (e.g. Japanese Patent Publication No. 51
23484), it is unavoidable that (2Z,5E)-farnesyl is produced in large quantities under the reaction conditions, and there is no known effective method for isolating and purifying all-transfarnesal. Therefore, highly pure total transfarnesal could not be obtained. For example, it is known that in precision distillation using a fractionating column, the target compound isomerized due to an intramolecular ene reaction as shown in the following formula.

An object of the present invention is to provide an effective method for producing total transfarnesal.

[Structure of the invention]

According to the invention, the above objects are achieved by (2Z/E mixed, 6E
) or (2Z/E mixture, 6Z/Em combination) -3,7,1
1-) Dimethyl-2,6,10-dodecatrienenitrile is separated by distillation (2E,6E)-, a.

7.11-) This is achieved by a method for producing all-transfarnesal, which is characterized by obtaining dimethyl-2,6,10-dodecatrienenitrile, reducing it using a reducing agent, and hydrolyzing it.

Upper Ht (2Z/E mixed, 6E)'t 7C
C (2Z/E mixed, 6 Z/E mixed) -3,7
,11-) IJ jteni-2,6,] ]0-dodecatrienenitrile, 3,7゜11-trimethyl-2
, 6,10-dodecatrienenitrile is referred to as farnesylnitrile. ) is (5E) t-R (s Z/E mixture) -6,10-SJ Chiru 5.9-'; 17 Dekaji:
1-7-2-one (hereinafter referred to as 6.10-dimethyl-
5,9-Undecadien-2-one is written as geranylacetone. ) with acetonitrile or general formula (R”0)2
By reacting with a cyanomethylphosphonic acid diester represented by P CH2CN (in the formula, R1 represents a lower argyl group), or by reacting the (5E)t or (
It can be easily obtained by reacting sZ/E mixture)-geranylacetone with cyanacetic acid or a lower alkyl ester thereof, hydrolyzing the resulting product if necessary, and then decarboxylating it. In addition, in the above, (
From 5E)-geranylacetone (2Z/E mixture).

6E)-Farnesyl nitrile is obtained, (5z/E mixture)-geranylacetone is obtained from (2Z/E mixture, 6Z/
E mixture)-farnesyl nitrile is obtained.

The method of the present invention can be represented by the diagram below to facilitate its understanding.

(2z/E mixture, 6 E) (2Z/EM, a
2S/E mixture) (2E16E) ↓Reducing agent↓Hydrolysis method, to heno ν.

(2E, 6E) (5E) or (5Z/E mix) - (2Z/E mix) from geranylacetone and acetonitrile.

6K)'l: or < 2Z/Em, 6Z/Ei) -
The synthesis reaction of 7-arnesylnitrile is carried out in the presence of a strong base. Usable strong bases include, for example, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkali metal lower alkoxides such as sodium methoxide, sodium ethoxide, sodium propoxide, and potassium t-butoxide; methyllithium; Examples include lower alkyl lithium such as butyl lithium; alkali metal amides such as sodium amide and potassium amide; alkali metal dialkylamides such as lithium diisopropyl amide; quaternary ammonium hydroxide; strong basic ion exchange resins.

Since these bases act as catalysts, they are not consumed during the reaction, but they are preferably used in an amount of 0.01 to 10 molar equivalents, preferably 0.1 to 5 molar equivalents, relative to geranyl acetone. Since in this reaction acetonitrile acts not only as a reaction component but also as a solvent, an excess of acetonitrile is usually preferably used for this purpose.

Therefore, a solvent may or may not be used, and examples of solvents that can be used include hydrocarbons such as hexane, heptane, benzene, toluene, and xylene. This reaction proceeds even at room temperature, but from the viewpoint of reaction rate,
Preferably, it is carried out at °C. If a sufficient reaction temperature cannot be obtained under atmospheric pressure, the reaction is preferably carried out under pressure, for example in an autoclave.

(5E) or (5z/E mixture)-geranilua 1 7 tons and the general formula (R”0>2 PCM2CN (in the formula,
R1 represents a lower alkyl group. ) from (2Z/E mixture) with cyanogen methyl phosphonic acid diester.

6E) '27'cid (2z/E mix + 6Z/E mix) - The synthesis reaction of farnesyl nitrile is carried out at a temperature of -80°C to 50°C in the presence of a base. R1 in the above formula: methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, 5ee-butyl group, t
-butyl group, etc. Examples of bases include alkali metal hydrides such as sodium hydride and potassium hydride; alkyl lithiums such as butyllithium and n-butyllithium; Grignard reagents such as methylmagnesium bromide and ethylmagnesium chloride; sodium amide, potassium amide, etc. Alkali metal amide; lower alkoxides of alkali metals such as sodium methoxide and potassium t-butoxide are used.
It is preferable to use cyanomethylphosphonic acid diester in an amount of 1.0 to 1.5 equivalents relative to geranyl acetone, and use the base in an amount of 1.0 to 2.0 equivalents relative to geranyl acetone. This reaction is carried out in the presence of a solvent. Examples of the solvent used include diethyl ether, tetrahydrofuran, dioxane, hexane, cyclohexane, benzene, toluene, methanol, ethanol, methylene chloride, dimethylformamide, dimethyl sulfoxide, pyridine, and hexamethylphosphoric triamide. In this reaction, (2E)-farnesyl nitrile is generally produced preferentially over (2z), but if left under the reaction conditions, the ratio of (2z) will gradually increase, so the next distillation will be difficult. (5E) or (5Z/E mixture)-geranylacetone and cyanoacetic acid or its lower alkyl ester represented by the general formula NCCH2C00R2 (in the formula, R2 represents a lower alkyl group after replacing the hydrogen atom) with ammonium acetate-acetic acid. 0 to 200°C, preferably 8°C in the presence of a catalytic to excess amount of a base or acid such as pyridine, morpholine, etc.
When reacted at 0 to 150°C, a compound represented by the general formula (in which R2 is as defined above) [(2Z/E mixed, 6E) monolithically or U(2Z/F
4 go, 6 Z/E mixture) integral] is produced. In this case, not only the compound of formula (Vl) but also farnesyl nitrile may be directly produced under the reaction conditions. In the formula (Vl), the compound with R2 = I (2z/E mixture,
6 E) 1 '* Ha (2Z/E mixed, 6z/E
mixture) - can be converted to farnesyl nitrile. In formula (■), R2 is a lower alkyl group (e.g. methyl group, ethyl group, n-propyl group, i-propyl group,
(n-butyl group, etc.), use potassium hydroxide.

(2Z/E mixed, 6 E)-ttake (2Z/E mixed.

5Z/E mixture)-farnesyl nitrile.

Distillation separation of (2E, 6E)-farnesyl nitrile from (2Z/E mixture, 6E mixture) -7 obtained as above (2Z/E mixture, 6Z/E mixture) This can be carried out using a commonly used distillation column. Distillation is usually carried out under reduced pressure, but in consideration of the thermal stability of farnesil, it is preferably carried out under reduced pressure of 1Qmml-1y or less, more preferably 0.
The farnesyl nitrile other than the (2E16E)-farnesyl nitrile recovered by distillation separation is carried out under a reduced pressure of 1 to 5 ml (f) by an isomerization reaction known per se.
, 6E)-farnesyl nitrile and then distilled again to obtain the separation of (2E, 6E)-farnesyl nitrile, so basically the entire amount (:2F, 5'E) - can be farnesyl nitrile. Examples of the isomerization catalyst used in the above isomerization reaction include thiophenol, p-) thiophenol, p-bromothiophenol, and ruthenium acetylacetonate (Chemistry Lett
ers, 1978.533).

As a reducing agent for reducing the (' 2 El 6E)-farnesyl nitrile obtained as above, diisobutylaluminum hydride or ld general formula MAJI
((OR3)a (where M represents an alkali metal,
R3 represents a lower alkyl group or an aryl group. ) is used. Here, M can be, for example, lithium, sodium, etc., and R3 is, for example, methyl group, ethyl group, n-propyl Nss 1-propyl group, n-butyl group, i-butyl group, 5ee-butyl group, t- Butyl group, n-pentyl group, n-hexyl group,
It can be a phenyl asp-t')h group, etc.

It is preferable to use the reducing agent in an amount of 1.0 to 1.3 equivalents based on (2E,6E)-farnesyl nitrile. Reduction is usually carried out in a solvent at a temperature of -20 to 60°C. Examples of solvents that can be used include hydrocarbons such as hexane, cyclohexane, benzene, and toluene, and ethers such as diethyl ether, diimpropyl ether, and dibutyl ether.

In the above reduction reaction, when diisobutylaluminum hydride is used as a reducing agent, a compound represented by the formula 0 (%) (in the formula, 1-Bu represents an isobutyl group) is produced, and as a reducing agent, a compound represented by the general formula MAJH (OR
3) When the compound represented by a is used, y (wherein M and R3 are as defined above), the desired total transfarnesal can be obtained with high purity.

After completion of the reduction reaction, it is preferable to carry out hydrolysis treatment immediately in order to avoid gradual isomerization of all transfarnesal to (2z,6E)-farnesal under the reaction conditions. Under strongly acidic conditions, isomerization of all-trans 7-arnesal to (2Z,6E)-farnesal occurs, so a strong acid aqueous solution cannot be used for hydrolysis. Examples of acids that can be used include organic or inorganic weak acids such as acetic acid, propionic acid, citric acid, tartaric acid, ammonium chloride water, and carbonated water. Depending on the concentration of acid used, it is better to use a buffer solution. Hydrolysis/0 Also, hydrolysis is preferably carried out at 0°C to 30°C.

After completion of the hydrolysis, total transfarnesal can be obtained by general separation operations such as extraction operations.

If further purification is required, all transfarnesal can be purified without reducing purity by promptly carrying out simple distillation under sufficient reduced pressure.

The above (5E) or (5Z/E mixed)-geranylacetone can be produced by the following method using, for example, geranyl chloride or linalool as a starting material.

(5E)-Geranylacetone (5E)-Geranylacetone [Effects of the Invention] The present invention provides a method for efficiently developing all-transfarnesal. According to the method of the present invention, highly pure total transfarnesal can be easily obtained (Examples) The present invention will be explained in detail below with reference to Examples.

Example 1 (i) (2Z/E mix 16 K) 77/L' screw/l/synthesis of nitrile Sodium hydride (60% nitrile dispersion) 37.12 (9
Diimpropyl cyanomethylphosphonate (purity 91%)] 8 (1 (799 mmol)) was slowly added dropwise to a solution of 28 mmO1) of 71.51 diimpropyl cyanomethylphosphonate (purity 91%), and after the addition was completed, it was stirred at room temperature. Stir for 30 minutes. Next,
Under water cooling % (5E)-geranylacetone 150? (77
3 mmol) was added dropwise to the above reaction solution, and then 1
．． Stirred for 5 hours. After the reaction is complete, pour the reaction solution into water, and
The extract was extracted with -hexane, washed sequentially with an aqueous solution of sodium hydroxide and saturated brine, and then dried over anhydrous sodium sulfate. After distilling off the solvent, vacuum distillation (103-105℃
/ 0.2 wmH9) And then! ! D (2Z/J
ill.

61)-7 Furnesyl nitrile (purity 98%, 2Z/2
g=23.8/76.2) 166F (750mm01
) was obtained (yield 97%) O Mass m/e:2]7(M”)+174181,6
9141 obtained in (1) above (2Z/E mixture,
6E)-Farnesylnitrile 166F (750mmo
1) was precisely distilled under reduced pressure of 0.5 w Hf using a distillation column with an inner diameter of 1.5 cm, length x, and 1 m (helivac packing).

629 was obtained as a total transfarnesyl nitrile fraction with a purity of over 95%.

MS NMR (90MHz) δ: 1.55 (S+6H)+
99m 1.61 (8, 3H) + 1.99 (S, 3H
).

1.86-2.03 (m, 4H), 2.03-2.2
0 (m, 4H) 4.81-5.13 (m, 31 () < m) Synthesis of all-trans 7 alnesal Under nitrogen atmosphere, all-trans farnesyl nitrile s, 43 y (25 ,0 mmol)
Diisobutylaluminum hydride (DIBAH
It is written as ) (25r/1ooy hexane solution) 16.0
Ill (28.2 mmol) was slowly added dropwise.

After stirring at room temperature for 1 hour, the mixture was stirred at 50°C for 3 hours. This reaction solution was cooled to 0°C, and 4.5 f (250 mm
A mixed solution of 5ml of tetrahydrofuran (THF) and 5ml of tetrahydrofuran (THF) was slowly added dropwise. Next, 1N acetic acid 175-(
175 mmol) and 3N ammonium acetate 175d
(0.25 mmol) and ice] The above reaction mixture was poured into a mixture of 502 and stirred at 0°C for 30 minutes.Then, the organic layer and the aqueous layer were separated, the organic layer was washed with water, and anhydrous sodium sulfate was added. After drying, the solvent was distilled off. The obtained residue is subjected to Kugelrohr distillation (bath temperature 150-160°C
10.3 ■W) In particular, 3.37 f (12.6 mmol) of total triyx7 arnetol was obtained. As a result of gas chromatography analysis, this product has 2E/2Z=9
A ratio of 4/6 was used (yield: 61 cm).

-Mass m/e: 220 [M+], 84
+ 69 + 411R (crn-'): 1680
, 1190. '11201.61 (s, 3H) 1.8
5-2.06 (m, 4H).

2.06-2.24 (m, 4H), 2.11
(S, 3f()4.80-5.20 (m, 2H
), 5.83 (d, J=8Hz, IH).

9.98 (d, J=8Hz, IH) Example 2 (i) (2Z/E mixture, 6E)-77* Hydroxide of 405' IJium(1,0 mole), 410
acetonitrile (10,0 mol) and (5E)-
A mixture of 190 ml (0.98 mol) of geranylacetone was heated and stirred at 80° C. for 3 days. This reaction mixture was heated to 550 ml.
2 into a 10% acetic acid aqueous solution, then benzene 100%
m/ was added and the liquid was separated. The aqueous layer was extracted with benzene. The benzene layers were combined, washed with water, and then dried over anhydrous sodium sulfate. After distilling off the solvent, the resulting residue was distilled under reduced pressure (100-105°C, 10.2 l). j
D (2Z/E mixture.

5E)-farnesylnitrile 3(1' (0.18 mol) was obtained. Reacted geranyl acetone 140f<0
．． 72 mol), the yield was 70 ml.

The ratio between (2E) unity and (2Z difference) was about 6=4.

By repeating the above reaction operation 7 times, a total of 280
$ silnitrile was obtained in (2Z/E mixed, 6E)-77 of f.

(ii) Synthesis of all-trans 7-arnesal IBAH
Hydrolysis, -2, 781, □ CHO Obtained in (1) above (2Z/E mixture, 6E) -
By distilling and separating 7-arnesyl nitrile 2 so y (2E/2226/4) in the same manner as in Example 1 (11), total transfarnesyl nitrile 752 with a purity of 95% or more was obtained. The remaining distilled fraction was subjected to repeated isomerization and distillation separation using thiophenol, and finally all-transfarnesyl nitrile [80f] having a purity of 95% or more was obtained.

Total transfarnesyl nitrile obtained above 5.4
3f (2s, ommol) in Example 1 (li+
), by reducing and hydrolyzing in the same manner as all-trans 7 alnesal 3.21 ? (14.6 mmol
) (obtain 2/2z=c+4/l*(yield 58 es)
.

Example 3 (1) (2Z/E mixture + 6") -77# Synthesis of nesyl nitrile To λ To λ/CN (5B) -G5 nyl 7 * door 39f (0.20 mol) dissolved in benzene 2001/ , ethyl cyanacetate 2
8F (0.25 mol), 52 grams of ammonium acetate and 5 grams of acetic acid were added, and the mixture was heated under reflux for 10 hours while removing water.

The reaction solution was separated, the organic layer was washed with water, and the solvent was distilled off. To the resulting residue was added sodium hydroxide 20f (0.50 mol),
After adding 100 d of propylene glycol and stirring at room temperature for 30 minutes, diluted hydrochloric acid was added to the reaction mixture to make it acidic, followed by extraction with benzene and washing with water. The residue obtained by distilling off the solvent was dissolved in 100d of pyridine, copper powder was added thereto, and the mixture was heated under reflux for 2 hours. The reaction solution was filtered, and the pyridine was distilled off. Hexane was added to the residue, which was washed with water and dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent was distilled under reduced pressure (99-105°C, 10.2 mHP).
, (2Z/E mixture, 6g) -:yr*silnitrile 2
4f (0.11 mol) was obtained (yield 55%) o (2E
) integral and (2z) integral was about 6!4T.

By repeating the above reaction operation 10 times, a total of 245
f O(2z/E mixed s 6 E ) 77 l4silnitrile was obtained.

Above (1) - t' Toku Rauta (2Z/Ei combination, 6 E
) -7 full $silni) Lil 220 tC2B/2Z
=6/4) was distilled and separated in the same manner as in Example 1 (11) to obtain all-trans 7-arnesyl nitrile 68F with a purity of 95% or higher.

All-trans 7-arnesyl nitrile obtained above 5.4
3? (25 mmol) as an example] ノ(iii)
By reducing and hydrolyzing in the same manner as
Alnesal 3.53 f (16,0 mmol) (
2F/2Z==93/7) (yield $64%)
).

Examples 4 to 12 and Comparative Example 1 Table 1 shows the results of reactions carried out in exactly the same manner as in Example 1 (111) except that the type and amount of acid were changed.

Examples 13 to 16 Table 2 shows the results of reactions in which sialumium was used and the reaction was carried out in the same manner as above, except that the reduction was carried out at room temperature in ether.

Table 2 Example 17 In (1) of Example 2, the same operation was repeated 7 times except that (5Z15E=4/6 mixture)-geranylacetone was used instead of (5E)-geranylacetone.
A total of 2952 (2Z/E mixed, 6z/E mixed)-7-arnesyl nitrile was obtained. This 040 (7) (2Z, 6Z
) integral: (2Z, 6E) and (,2E, 6Z) integral: (2E, 6E) integral ratio was approximately 15:49:36. The farnesyl nitrile was precision distilled in the same manner as in Example 1 (1θ) to obtain all-trans farnesyl nitrile 72.3F with a purity of 96.5%. [This thing is (2Z, 6Z) together: (2Z, 6E) o, mbi (
2E, 6Z) integral: (2E, 5E) integral ratio is approximately 20
: 67;
6E) Oh! The ratio of 1 (2E, 6E) and 1 (2E, 6Z) was 17:52:31. After simple distillation of this reaction solution to separate the catalyst, the obtained farnesyl nitrile 211.4F was subjected to the same precision distillation as above to obtain an additional amount of all-trans farnesyl nitrile 6 with a purity of 95%.
0.6r as i*.

96% pure transfarnesyl nitrile obtained by the above method 1329 n-hexane 650 rILl
The solution was prepared according to the reaction procedure of Example 1, and 21
1) IBAH (25f/1
After 390 Inl of 00ml hexane solution was added dropwise at room temperature, the mixture was reacted at 50°C for 5 hours. Example 1 ゛(rr
r),! ! : Post-treatment was performed in the same manner to obtain 116.5f of crude transfarnesal. This is also oit
(zZ, 6E) Integral: (2E, 6E) Integral o ratio is 4
．． I passed at 3:95.7. The crude farnesal was subjected to simple distillation under reduced pressure, and the boiling point was 130 to 150°C, 10.2wnH2.
Total transfarnesal with a purity of 98% as a fraction of 8
4.38' C (2Z, 6E) together: (2E, 6E
) An integral ratio of 5.4:94.6) was obtained.

Reference Example 1 Thermal stability ti of Falsol
13) was heated at 180°C for 5 hours under a nitrogen atmosphere.

The farnesal before and after heating was analyzed by gas chromatography [column: 0V-17,
After 2 minutes at a column temperature of 100°C, the temperature was raised (lO°C/min) to 200°C.

Gas chromatograms shown in FIGS. 1 and 2 of the accompanying drawings were obtained. FIG. 1 is a gas chromatogram obtained for Farnesal before heating, and FIG. 2 is a gas chromatogram obtained for Farnesal after heating. In these figures, 1 is a peak showing total transfarnesal, a peak showing 2i'1(IZ, 6E)-farnesal, and 3 is a peak showing the cyclized product shown below. These gas chromatograms were obtained by the above heating (2E).

6E) Integrity': + (2z, 6F) - Mi conversion to the body,
1: This indicates that cyclization by intramolecular ene reaction was promoted.

When performing precision distillation of farnesal using the same distillation column as in Example 1 (11), the temperature of the distillation pot will be 180°C under a reduced pressure of 0.5 am Hy. As is clear, isomer separation of farnesal by distillation is difficult.

[Brief explanation of drawings]

Figures 1 and 2 of the attached drawings are gas chromatograms obtained for Farnesal before and after heating when Farnesal was heated at 180°C for 5 hours in a nitrogen atmosphere, and Figure 1 shows the gas chromatograms of Farnesal before and after heating. Figure 2 shows the product after heating. ■...Peak indicating (2E, 6E)-farnesal. 2...Peak showing (22,6E)-farnesal, 3...Peak showing cyclization product. Patent Applicant Rira Co., Ltd. Representative Patent Attorney Ken Honda No. 10 Procedural Amendment (Voluntary) June 27, 1980 1. Indication of the Case 1982 Patent Application No. 77877 2. Name of the Invention (2E , 6E) -3,7,11-trilf Roux 2,6.
Manufacturing method for 10-dodecatriene-1-R 3, relationship with the amended case Patent applicant: 1621 Sakazu, Kurashiki City (108) RiRa Co., Ltd. Representative Director Ueno et al. - (Tokyo contact information) Co., Ltd. Kuraray Patent Department Li Tokyo 03 (27713182 5, Detailed explanation of the invention column 6 of the specification subject to amendment, Contents of the amendment (1) Formula in the first line of page 5 of the specification (2) Page 20 of the specification 5th row from the bottom rO, 25J
is changed to r525J. (8) r12.6 j on page 21, line 2 of the specification
Changed to 5.3J.

Claims (1)

[Claims] (1) (2z/E mixture, c;E)tU (2Z/E mixture, 6z/E mixture)-3,7,11-trimethyl-2,
6,10-dodecatrienenitrile was separated by distillation (2
F, 6E)-3,7,・11-trimethyl-2,6,1
It is characterized by obtaining 0-dodecatrienenitrile, reducing it using a reducing agent, and hydrolyzing it (2E, 6E
)-3,7,11-trimethyl-2,6,10-dodecatriene-1-al. (2) A patent in which the reducing agent is diisobutylaluminum hydride or a compound represented by the general formula MAJH(OR3)a (wherein M represents an alkali metal atom and R3 represents a lower alkyl group or an aryl group) The manufacturing method according to claim 1. (81 (2Z/Effi combined, 6E) t or (2Z/E mixed, 6z/E・combined) 3,7.11)su) -f- to-
2,6,10-dodecatrienenitrile is (5E)'j
1t (5Z/E mixture) -6,10-dimethyl-5,
The reaction between 9-wandecadien-2-one and a7tonitryl or a cyanomethylphosphonic acid diester represented by the general formula (R"0)2PCH2CN (wherein R1 represents a lower alkyl group) (4) (2Z/E mixing, 6E)!fc is <2Z/E mixing + 6 Z/E mixing) -3, 7,11-)dimethyl-2,6,10-dodecatrienenitrile is (
5E) 'J* (5Z/E mixture) -6,10-dimethyJL/ -5,9-undecadien-2-one and cyanoacetic acid or its lower alkyl ester are reacted to form a product obtained by The manufacturing method according to claim 1 or 2, which is obtained by hydrolyzing the product and then decarboxylating it.