JPH07188119A - Amine derivative and its production - Google Patents

Abstract

PURPOSE:To obtain a new amine derivative producible by a single stage reaction in high selectivity and easily convertible to geranylgeraniol useful as an intermediate for pharmaceuticals such as vitamin K2. CONSTITUTION:This (2E,6E,10E,14E)-3,7,11,15-tetramethyl-2,6,10,14- hexadecatetraenylamine derivative is expressed by formula I (R<1> and R<2> are each a 1-6C alkyl or together with bonding N atom form a 4 to 6-membered ring), e.g. N,N-diethylgeranylgeranylamine. The compound of formula I can be produced by reacting a geranyllinalylacyl derivative of formula II (R<3> is a 1-4C alkyl, a 1-4C alkoxy or phenyl) with a sec-amine of formula III in the presence of a palladium compound and a t-phosphine. The geranyllinalylacyl derivative of formula II is easily producible by acylating geranyllinalool.

Description

Detailed Description of the Invention

[0001]

The present invention relates to the following formula (4) useful as an intermediate for pharmaceuticals such as vitamin K ₂

[0002]

[Chemical 4]

A novel intermediate for producing geranylgeraniol represented by (2E, 6E, 10E, 1)
4E) -3,7,11,15-tetramethyl-2,6.
The present invention relates to a 10,14-hexadecatetraenylamine derivative (hereinafter referred to as geranylgeranylamine derivative) and a method for producing the same.

[0004]

2. Description of the Related Art Geranylgeranylamine represented by the following formula (5) is described in Japan. J. Pharmacol., 33,549-556 (1983) as a compound similar in structure to the amine derivative of the present invention. Those are described as being useful as anti-ulcer agents.

[0005]

[Chemical 5]

As a method for producing geranylgeranylamine (5), JP-A-61-227551 discloses a Gabriel synthesis method represented by the following formula (6), or a method for producing isoprenylamine by azidation. ing.

[0007]

[Chemical 6]

(X represents a halogen atom, and n represents 3 or 4.)

However, according to this production method, geranylgeranylamine (5) cannot be obtained unless the three-dimensional structure of the halogenated isoprenyl as a substrate is an allol trans isomer, and the geranylgeranyl halide as the allol trans isomer of the substrate is not obtained. Is difficult to prepare.

A method for producing N, N-dialkylgeranylamine (7) having a smaller number of carbon atoms than the amine derivative of the present invention represented by the following formula (7) is disclosed in JP-A-54-76515 and Bull. Chem. .Soc. Japan, 46, 222-225 (1975).

[0011]

[Chemical 7]

However, in order to produce a geranylgeranylamine derivative by applying the production methods described in these references, the raw material is represented by the following formula (8) (6E, 10E, 14E)-
3-methylene-7,11,15-trimethyl-1,6
The production of 10,14-hexadecatetraene is very difficult.

[0013]

[Chemical 8]

Further, (6E, 10E, 14E) -3 described in Example 1 of JP-A-3-148228.
-Methylene-7,11,15-trimethyl-1,6,1
Although 0,14-hexadecatetraene may be used as a starting material, this compound is a mixture of cis isomers and trans isomers, and it is impossible to selectively produce a geranylgeranylamine derivative.

Allylamines are prepared by reacting allyl alcohol, allyl chloride, allyl acetate or allylphosphonate with a primary or secondary amine in the presence of a palladium compound and a tertiary phosphine. The method (the following formula (9)) is disclosed in, for example, JP-A-1-153660
Japanese Patent Laid-Open No. 1-165555, Tetarahedron
Letters, 3821-3824 (1970), 2745-2748 (1983)
Etc.

[0016]

[Chemical 9]

However, the production method described in these documents is a reaction in which an amine is nucleophilically substituted with a hydroxy group in order to produce an amine from alcohol, and the stereo structure of the allyl compound as a substrate is also okay. A geranylgeranylamine derivative cannot be obtained unless it is in the trans form.

Also, Tetrahedron Letters, 4, 321-324 (19
79) describes a double bond isomerization reaction involving rearrangement of acetoxy group of acetic acid ester of allylic alcohol using a divalent palladium compound represented by the following formula (10).

[0019]

[Chemical 10]

However, all of the allyl compounds described in this document have only one double bond, and when there are a plurality of double bonds such as geranyllinalyl group, the catalytic activity is markedly reduced and a large amount of them are produced. There is a problem that a catalyst must be used.

On the other hand, there are many examples of the method for producing geranylgeraniol from geranyl linalool represented by the following formula (11), for example, Helv. Chim. Acta, 22, 392.
~ 396 (1939), Chemistry Letters, 357 ~ 360 (1982)
Etc.

[0022]

[Chemical 11]

However, these production methods produce a mixture of cis and trans isomers, and a large amount of geranylnerol represented by the following formula (12) in which one of the double bonds is cis is produced as a by-product. Not the law.

[0024]

[Chemical 12]

[0025]

DISCLOSURE OF THE INVENTION The present invention provides a novel intermediate which is a raw material for producing geranylgeraniol useful as a pharmaceutical intermediate in a high yield and with high selectivity, and a method for producing the intermediate. The challenge is to provide.

[0026]

Means for Solving the Problems As a result of intensive studies on such problems, the present inventors have used an acyl derivative of geranyl linalool, which is easily available, as a raw material, which is used as a secondary amine or a palladium compound. It was found that a geranylgeranylamine derivative, which can be a raw material for geranylgeraniol (4), can be obtained in a high yield and a high selectivity in only one step by reacting it with a tertiary phosphine and to complete the present invention. I arrived.

That is, the present invention is as follows. (1) The following general formula (1)

[0028]

[Chemical 13]

(In the formula, R ¹ and R ² may be the same or different and each represents an alkyl group having 1 to 6 carbon atoms, or
^The nitrogen atom in which ¹ and R ² are bonded together with R ¹ and R ² is 4 to
A 6-membered ring may be formed. ) A geranylgeranylamine derivative represented by:

(2) The following general formula (2)

[0031]

[Chemical 14]

(Wherein R ³ represents an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms or a phenyl group which may have a substituent),
In the presence of a palladium compound and a tertiary phosphine,
The following general formula (3)

[0033]

[Chemical 15]

A method for producing a geranylgeranylamine derivative, which comprises reacting with a secondary amine represented by the formula (wherein R ¹ and R ² have the same meanings as described above).

The present invention will be described in detail below. Examples of the novel geranylgeranylamine derivative of the present invention include the following. That is, to give some specific examples, N, N-dimethylgeranylgeranylamine, N, N-diethylgeranylgeranylamine,
N, N-dipropylgeranylgeranylamine, N, N-
Diisopropylgeranylgeranylamine, N, N-dibutylgeranylgeranylamine, N, N-diisobutylgeranylgeranylamine, N, N-di-sec-butylgeranylgeranylamine, N, N-di-tert-butylgeranylgeranylamine, N, N-methylethyl Geranylgeranylamine, N, N-methylpropylgeranylgeranylamine, N, N-methylbutylgeranylamine,
Examples thereof include N, N-ethylbutylgeranylgeranylamine, N-geranylgeranylpiperidine, N-geranylgeranylpyrrolidine, N-geranylgeranylazetidine, and N-geranylgeranylmorpholine.

Such a geranylgeranylamine derivative (1) of the present invention is obtained by reacting a geranyllinalyl acyl derivative (2) with a secondary amine (3) in the presence of a palladium compound and a tertiary phosphine. It can be manufactured.

The geranyl linalyl acyl derivative (2), which is the starting material of the present invention, can be produced by acylating geranyl linalool (11) by a known method. For example, geranyl linalool (11) is used in the presence of a base such as n-butyllithium, sodium hydride, pyridine, dimethylaminopyridine or sodium acetate or potassium acetate at room temperature or under heating to obtain an acetic anhydride or an acetyl chloride or other acyl group. It is produced by reacting an agent. The obtained geranyl linaryl acyl derivative (2) can be used in the next reaction as a crude product or after distillation.

Further, the secondary amine (3) which is another raw material
In the present invention, a lower alkylamine is used as
The lower alkylamine is used in a molar ratio of 1.5 to 4 equivalents with respect to the geranyl linalyl acyl derivative (2),
The amount is preferably 2-3 equivalents. Second used for reaction
When the amount of the secondary amine is less than 1.5 equivalents in terms of molar ratio, the secondary amine is consumed by the carboxylic acid generated during the reaction, which is not preferable. Also, an amount of secondary amine greater than 4 equivalents in molar ratio does not give good results.

As one component of the catalyst, a palladium compound is used in the present invention. Specifically, palladium carboxylates such as palladium acetate, palladium propionate and palladium trifluoroacetate, palladium chloride, palladium bromide, iodine Palladium halides such as palladium halides, palladium nitrate, palladium acetylacetone
, Palladium dibenzylacetone and the like can be used. Most preferred is the use of palladium acetate. The amount of the palladium compound used is 0.0001 mol to 1 mol of the geranyl linalyl acyl derivative.
The amount is preferably in the range of 0.1 mol, preferably 0.00
It is preferable to set it to 05 mol to 0.005 mol.

The tertiary phosphine, which is another catalyst component in the present invention, has the following general formula (13):

[0041]

[Chemical 16]

(Wherein Ar ¹ , Ar ² and Ar ³ represent an optionally substituted phenyl group) or the following general formula (1
4)

[0043]

[Chemical 17]

(Wherein Ar ⁴ , Ar ⁵ , Ar ⁶ and Ar ⁷ represent an optionally substituted phenyl group or a cyclohexyl group, and A represents an alkylene group having 1 to 4 carbon atoms). Is used.

Of these tertiary phosphines, preferred phosphines are, for example, triphenylphosphine,
Tri (ortho-tolyl) phosphine, tri (meta-tolyl)
Phosphine, tri (meth, tert-butylphenyl) phosphine, bis (diphenylphosphino) methane, bis (diphenylphosphino) ethane, bis (diphenylphosphino) propane, bis (diphenylphosphino) butane, bis (dicyclohexylphosphino) ) Ethane, etc., but most preferred is triphenylphosphine. The amount of the tertiary phosphine used is preferably in the range of 1 to 10 mol, and more preferably 2 to 4 mol, per 1 mol of the palladium compound.

In the present invention, the reaction is usually carried out in the presence or absence of a solvent. Examples of the solvent usable in the present invention include aliphatic hydrocarbons such as pentane, hexane, heptane, octane, decane, cyclohexane and decalin; aromatic hydrocarbons such as benzene, toluene, xylene, cumene and t-butylbenzene; Ethers such as diethyl ether, diisopropyl ether, dibutyl ether, isoamyl ether, dimethoxyethane, diethylene glycol dimethyl ether, petroleum ether, ligroin, tetrahydrofuran, dioxane; dimethylformamide, dimethylacetamide. , N-methylpyrrolidone and other amides; ethyl formate, methyl acetate, ethyl acetate and other esters, and the like. Preferred are ethers such as diisopropyl ether.

To prepare the geranylgeranylamine derivative (1) of the present invention, a mixture of the above-mentioned geranyllinalyl acyl derivative (2), the secondary amine (3), the palladium compound and the tertiary phosphine is used without solvent. Alternatively, in the presence of a solvent, under a nitrogen stream, usually 20 ° C to 100
It can be obtained by stirring and reacting at a temperature of 20 ° C., preferably 20 ° C. to 80 ° C. The time required for the reaction varies depending on the presence or absence of a solvent and the reaction temperature, but is generally about 1
Hours to 18 hours are recommended. The mixture after the completion of the reaction can be treated by a conventional method such as distillation or column chromatography to obtain the desired geranylgeranylamine derivative with high purity.

To produce geranylgeraniol from the geranylgeranylamine derivative thus obtained, there is a known method, for example, a method for producing geraniol from N, N-dialkylgeranylamine, which is disclosed in JP-A-54-
76515 or Chemistry Letters, 1031-
1032 (1975)) and can be produced in high yield and without causing isomerization. That is, a method for producing a geranylgeraniol by reacting a chloroformate with a geranylgeranylamine derivative and then hydrolyzing the geranylgeranyl acetate by reacting with potassium acetate, or a method for producing a geranylgeranylamine derivative with N-oxide with hydrogen peroxide. Then, it is heat-transferred to form a geranylgeranyloxyamine derivative, and then treated with zinc and acetic acid to produce geranylgeraniol.

[0049]

INDUSTRIAL APPLICABILITY According to the present invention, a novel geranylgeranylamine derivative, which is a compound that can be easily converted into geranylgeraniol useful as an intermediate for pharmaceuticals, is highly selective,
Moreover, it can be obtained by a reaction in only one step.

[0050]

EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples. The physical data in the examples are measured with the following measuring instruments and methods. (1) Conversion / selectivity: Gas chromatography-58
90 (manufactured by Hulett Packard) column; Silicon OV-1 (0.25 mm x 25 m)
(Manufactured by GL Sciences Inc.) Temperature: increased from 150 ° C to 220 ° C by 4 ° C / min (2) Infrared absorption spectrum (IR): IR-810 type (manufactured by JASCO Corporation) (3) Mass spectrum ( MS): M-80 mass spectrometer (ionization voltage 20 eV) (manufactured by Hitachi, Ltd.) (4) Nuclear magnetic resonance spectrum ( ¹ H-NMR): AM
-400 type (400 MHz) (manufactured by Bruker) Internal standard substance; tetramethylsilane

[0051]

Reference Example 1 Production of Geranyl Linalyl Acetate After dissolving 58.0 g (0.2 mol) of geranyl linalool in 100 ml of toluene, 38 ml of acetic anhydride (0.4 mol) was prepared.
Mol) and 18.1 g (0.22 mol) of sodium acetate were added, and the mixture was heated under reflux for 24 hours with stirring. After confirming the disappearance of the raw materials by gas chromatography and returning the reaction solution to room temperature, it was washed with 10% aqueous sodium carbonate and saturated brine in that order, the organic layer was dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure. Then, it was distilled under reduced pressure to obtain 60.8 g (yield 92%) of geranyllinalyl acetate as a colorless oily substance having a purity of 93%.

The physical data of the obtained geranyl linalyl acetate are as follows. Boiling point: 157-159 ° C (0.4 mmHg) Nuclear magnetic resonance spectrum: ¹ H-NMR (δ; CDC
l ₃ ): 1.54, 1.59, 1.68 (15H,
s), 1.96 to 2.06 (14H, m), 5.09 to
5.17 (5H, m), 5.98 (1H, dd, J = 1
1,17.5 Hz) Infrared absorption spectrum: (ν _max cm ^-1 ; neat): 2
925, 1710, 1650 Mass spectrum: (m / e): 332 (M ⁺ ), 30
6,272,136,107,93,69,43

[0053]

Reference Example 2 Production of Geranyl Linalyl Acetate After 145 g (0.5 mol) of geranyl linalool was dissolved in 150 ml of heptane, 76.5 g (0.7
5 mol), 101 g of triethylamine (1.0 mol),
Dimethylaminopyridine (6.1 g, 50 mmol) was added, and the mixture was stirred at room temperature for 40 hours. After confirming the disappearance of the raw materials by gas chromatography, the solvent was evaporated under reduced pressure, the residue was diluted with ethyl acetate, washed with 2N hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate, and reduced pressure. The lower solvent was concentrated to obtain 169 g of a pale yellow oily substance. Distillation under reduced pressure gave 151 g (yield 91%) of geranyl linalyl acetate as a colorless oily substance having a purity of 92%.

[0054]

Reference Example 3 Production of Geranyl Linalyl Benzoate A mixture of 14.5 g (50 mmol) geranyl linalool and 50 ml of anhydrous tetrahydrofuran was placed at -20 ° C.
And stirred under stirring with n-butyllithium (1.6 mol,
Hexane solution) (34.4 ml, 55 mmol) was added dropwise, and the mixture was returned to room temperature and then stirred for 1.5 hours. -20 again
After cooling to ℃, 10.6 ml (60 mmol) of benzoyl chloride was added dropwise, the mixture was returned to room temperature and stirred for 2 hours, after confirming disappearance of the raw materials, the solvent was concentrated under reduced pressure, and the residue was extracted with ethyl acetate, It was washed with water, the organic layer was dried over magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain 14.6 g (yield 78%) of geranyllinalyl benzoate as a colorless oil.

The physical data of the obtained geranyl linalyl benzoate are as follows. Nuclear magnetic resonance spectrum: ¹ H-NMR (δ; CDC
l ₃ ): 1.59, 1.68, 1.69 (15H,
s), 1.95 to 2.11 (14H, m), 5.08 to
5.29 (5H, m), 6.10 (1H, dd, J = 1
1,17.5 Hz) Infrared absorption spectrum: (ν _max cm ^-1 ; neat): 2
920, 1720 Mass spectrum: (m / e): 394 (M ⁺ ), 27
2,257,161,137,109,93,69

[0056]

[Reference Examples 4 to 8] The same procedures as in Reference Example 2 were carried out to obtain geranyllinalyl acyl derivatives shown in Table 1. Table 1 shows physical data of the obtained acyl derivative.

[0057]

Example 1 In a 500 ml pressure-resistant sealed tube under a nitrogen atmosphere, 50 g (0.15 mol) of geranyl linalyl acetate obtained in Reference Example 1, 100 mg (0.45 mmol) of palladium acetate, and 480 mg (0.6 mg of triphenylphosphine). Mmol), 35 ml (0.34 mol) of diethylamine and 200 ml of diisopropyl ether were added under a nitrogen atmosphere, and the mixture was stirred at 30 ° C. for 18 hours. When measured by gas chromatography, the conversion rate was 100% and the trans /
The cis ratio was 93/7 and the trans isomer selectivity was 82%. The reaction solution was returned to room temperature, washed with saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to give a pale yellow oily substance 43. 0.2 g (yield 85%) was obtained.

Physical data of the obtained N, N-diethylgeranylgeranylamine are as follows. Boiling point: 158 to 160 ° C. (0.07 mmHg) Nuclear magnetic resonance spectrum: ¹ H-NMR (δ; CDC
l ₃ ): 1.03 (6H, t, J = 7.1 Hz), 1.
60, 1.64, 1.68 (15H, s), 1.96 ~
2.10 (12H, m), 2.51 (4H, q, J =
7.1, 14.3 Hz), 3.06 (2H, d, J =
6.8 Hz), 5.09 to 5.12 (3H, m), 5.
12 (1H, t, J = 6.8 Hz) Infrared absorption spectrum: (ν _max cm ^-1 ; neat): 2
970, 1665 Mass spectrum: (m / e): 345 (M ⁺ ), 33
0,276,208,140,126,107

[0059]

Examples 2 to 6 Instead of the diethylamine used in Example 1, dimethylamine, butylamine, pyrrolidine, piperidine and morpholine were used, respectively. Further, the same operation as in Example 1 was carried out except for the solvent, temperature and time. The results are shown in Table 2.

[0060]

Examples 7 to 9: Instead of the palladium acetate used in Example 1, palladium propionate, palladium trifluoroacetate and palladium acetylacetonate were used,
It carried out like Example 1. The results are shown in Table 3.

[0061]

Examples 10 to 13 The procedure of Example 1 was repeated, except that the tertiary phosphine shown in Table 4 was used instead of the triphenylphosphine used in Example 1. The results are shown in Table 4. In Table 4, (m-tol) ₃ P is tri (methacryl) phosphine, (m-tBuPh) ₃ P is tri (meth, tert-butylphenyl) phosphine, DPPE is bis (diphenylphosphino) ethane and DPPB. Represents bis (diphenylphosphino) butane.

[0062]

Examples 14 to 22 The same operations as in Example 8 were carried out except for the solvent, temperature and time shown in Table 5. The results are shown in Table 5.

[0063]

Comparative Example 1 50 g (0.15 mol) of geranyl linalyl acetate obtained in Reference Example 1, isopropyl ether 125
ml and 2.5 g of PdCl ₂ (CH ₃ CN) ₂ (9.
(6 mmol) was put in a 500 ml pressure bottle and purged with nitrogen, and then stirred at 65 ° C. for 18 hours. When the obtained reaction liquid was analyzed by gas chromatography, the conversion rate was 97.
%, The trans / cis ratio was 84/16. After returning the reaction solution to room temperature, the insoluble matter was filtered, the filtrate was concentrated under reduced pressure, and the residue was distilled under reduced pressure. 38.4 g (77% yield) of geranylgeranyl acetate having a purity of 75% was obtained.

[0064]

Comparative Examples 2 to 11 The procedure of Comparative Example 1 was repeated, except that the palladium catalyst, solvent, temperature, time and additives were changed.
The obtained results are shown in Table 6.

[0065]

Example 23 Production of Geranylgeraniol (1) Production of Geranylgeranyl Acetate 40 g (0.116 mol) of N, N-diethylgeranylgeranylamine obtained in Example 1 and ethyl chlorocarbonate 2
2.2 ml (0.232 mol) was dissolved in 160 ml of diisopropyl ether and stirred at room temperature for 24 hours. After confirming disappearance of the raw materials by gas chromatography, the mixture was concentrated under reduced pressure to obtain 33.2 g of geranylgeranyl chloride, which was directly subjected to the next reaction without purification. 33.2 g of this geranylgeranyl chloride was dissolved in 160 ml of acetonitrile, to which 11.4 g (0.116 mol) of potassium acetate and 1.2 g (4.54 mmol) of 18-crown-6 were added, and the mixture was stirred at 50 ° C. for 5 minutes. The mixture was heated and stirred for an hour. After confirming the disappearance of the raw materials by gas chromatography, the precipitated salt was filtered, concentrated under reduced pressure, and dissolved in 300 ml of toluene,
After washing with a saturated aqueous solution of ammonium chloride, it was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and 30.4 g (yield 82%) of geranylgeranyl acetate was obtained by vacuum distillation.

The physical data of the obtained geranyl geranyl acetate are as follows. Boiling point: 170 to 173 ° C. (0.9 mmHg) Nuclear magnetic resonance spectrum: ¹ H-NMR (δ; CDC
l ₃ ): 1.60, 1.70, 1.77 (15H,
s), 1.97 to 2.13 (12H, m), 4.59
(2H, d, J = 7.1 Hz), 5.08 to 5.13
(3H, m), 5.34 (1H, t, J = 5.8Hz) Infrared absorption spectrum: (ν _max cm ^-1 ; neat): 2
920, 1745, 1670 Mass spectrum: (m / e): 332 (M ⁺ ), 27
2,203,136,107,93,69,43

(2) Preparation of geranylgeraniol 25 g of geranylgeranyl acetate obtained in (1) (75.
(3 mmol) was dissolved in 60 ml of methanol, 6.0 g (91.1 mmol) of potassium hydroxide was added thereto, and the mixture was stirred at room temperature for 1.5 hours. After confirming the disappearance of the raw materials by gas chromatography, the solvent was distilled off under reduced pressure, the residue was extracted with toluene, washed with water and dried over magnesium sulfate,
20. Distilled under reduced pressure to obtain 96% pure geranylgeraniol.
5 g (yield 94%) was obtained.

The physical data of the obtained geranylgeraniol is as follows. Boiling point: 153-155 ° C. (0.3 mmHg) Nuclear magnetic resonance spectrum: ¹ H-NMR (δ; CDC
_{l 3): 1.60,1.68 (15H,} s), 1.95
~ 2.13 (12H, m), 4.15 (2H, d, J =
6.9 Hz), 5.09 to 5.13 (3H, m), 5.
42 (1H, t, J = 6.9 Hz) Infrared absorption spectrum: (ν _max cm ^-1 ; neat): 3
360, 2920, 1670 Mass spectrum: (m / e): 290 (M ⁺ ), 27
2,203,136,107,93,69

[0069]

[Table 1]

[0070]

[Table 2]

[0071]

[Table 3]

[0072]

[Table 4]

[0073]

[Table 5]

[0074]

[Table 6]

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Reference number in the agency FI technical display location // C07B 61/00 300 (72) Inventor Mutsumi Harada 1-4-11 Nishihachiman, Hiratsuka-shi, Kanagawa No.Takasago International Corporation Basic Research Laboratory

Claims (2)

[Claims] 1. The following general formula (1): (In the formula, R ¹ and R ² may be the same or different and each represents an alkyl group having 1 to 6 carbon atoms, or a nitrogen atom to which R ¹ and R ² are bonded and R ¹ and R ² are 4 ~ May form a 6-membered ring) (2E, 6E, 10E, 14
E) -3,7,11,15-tetramethyl-2,6,1
0,14-hexadecatetraenylamine derivative. 2. The following general formula (2): (In the formula, R ³ represents an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or a phenyl group which may have a substituent). In the presence of a tertiary phosphine, the following general formula (3): (Wherein R ¹ and R ² have the same meanings as described above), and the reaction is carried out with a secondary amine (2E, 6E, 10E, 14E) -3,7,11. , 15
-Method for producing tetramethyl-2,6,10,14-hexadecatetraenylamine derivative.