JPS6241709B2 - - Google Patents

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a compound having the formula (In the formula, R represents H or an alkyl group having 1 to 4 carbon atoms.) This relates to a branched sulfur-containing compound represented by:

Terpenoids containing sulfur were discovered in grapefruit by E. Demole et al., and are positioned as the main aroma component of grapefruit. (E. Demole et.al, Helv.chim.Acta, 65;
1785 (1982)) Furthermore, bicyclic terpenoids containing sulfur (formulas (), ()) have been discovered, and their fragrant aroma is of interest. (OPStrauz, et.al,
Tetrahedron Lett., 24, 651 (1983)) Acid-catalyzed cyclization of polyolefins is known as an effective method for synthesizing such polycyclic compounds having a large number of asymmetric carbon atoms. Therefore, synthetic raw materials or synthetic intermediates having double bonds at appropriate positions are required. In this respect, compounds () and () are extremely useful compounds as synthetic intermediates for compounds () and (). Concerted cyclization reaction, a known method [A.Saito
et.al.Chem.Lett., 1065 (1987)],
It is easy to synthesize compounds () and () by treating them with an acid catalyst.

As mentioned above, the compounds () and ()
is considered to be an extremely useful substance as a synthetic intermediate for compounds () and (), and an object of the present invention is also to provide compounds () and ().

[Prior art]

Compounds () and () of the present invention were newly synthesized by the present inventors, and therefore there is no prior art.

[Problem that the invention seeks to solve]

An object of the present invention is to provide compounds () and compounds that are intermediates for easily producing (chemical synthesis).

[Means for solving problems]

Compounds () and () of the present invention are considered to be compounds that can be synthesized by various methods, and will be briefly explained using the flow sheet shown below as an example.

4,5-dimethyl-3,7-nonadienoic acid [A. Saito, et.al,
Chem. Lett., 1065 (1978)] (hereinafter compound ()
) is esterified in alcohol in the presence of an acid, and further hydride-reduced with lithium aluminum hydride or the like to convert it to alcohol (homogeraniol). The desired compound () can be obtained by converting this alcohol into a mesylated product with mesyl chloride triethylamine, then reacting with sodium salt of benzyl mercaptan to obtain a benzyl thioether product, and further reducing with sodium in liquid ammonia. .

Further, the compound () is reacted with 2 equivalents of alkyl lithium to form a ketone, and this ketone is further converted into an alcohol by hydride reduction with lithium aluminum hydride or the like. Hereinafter, compound () can be obtained by converting alcohol into thiol using a method similar to the synthesis of compound ().

[Example 1] 3.64 g (20 mmol) of the compound () was dissolved in 50 ml of ethyl alcohol, and 5 ml of titanyl chloride was added dropwise while stirring and cooling on ice. After reacting at room temperature (18°C) for 2 hours, the reaction solution was poured onto ice and extracted with 200ml of ethyl ether. Ethyl ether was washed once with a saturated aqueous sodium bicarbonate solution and three times with brine, and then dried over anhydrous magnesium sulfate. After drying, it was filtered and the liquid was concentrated under reduced pressure to obtain 4.10 g (19.5 mmol) of ethyl ester compound (4,8-dimethyl-3,7-nonadienoic acid ethyl ester). (Compound()
The yield is 97.5%).

Next, 4.1 g of lithium aluminum hydride was added to a solution of 1.9 g (50 mmol) suspended in 100 ml of ethyl ether while stirring under ice cooling.
(19 mmol) of 4,8-dimethyl-3,7-nonadienoic acid ethyl ester is added dropwise. After dripping,
After reacting at 0° C. for 1 hour, the reaction solution was poured onto ice and extracted with 100 ml of ethyl ether. Ethyl ether was washed three times with brine and dried over anhydrous magnesium sulfate. After drying, it was filtered and the liquid was concentrated under reduced pressure to obtain 3.23 g (19 mmol) of alcohol (homogeranyl alcohol). (4,8
The yield based on -dimethyl-3,7-nonadienoic acid ethyl ester was 97.5%).

Next, 3.23 g (19 mmol) of homogeraniol and 2.53 g (25 mmol) of triethylamine were added.
Dissolved in 50 ml of dichloromethane and, under stirring, −
While maintaining the temperature between 10℃ and -20℃, mesyl chloride,
Add 2.86 g (25 mmol) dropwise. 0℃～-10℃
After reacting for 1 hour, pour the reaction solution onto ice.
Extracted with 200ml of ethyl ether. Ethyl ether was washed three times with brine and then dried over anhydrous magnesium sulfate. After drying, it was filtered and the liquid was concentrated under reduced pressure to obtain 4.67 g (19 mmol) of mesylated product.

Next, add 2.48 g (20 mmol) of benzyl mercaptan and 0.96 g (20 mmol) of 50% sodium hydride.
mmol) in tetrahydrofuran (THF) 50ml
4.67 g (19 mmol) of mesylated product was added dropwise to the benzyl mercaptan sodium salt obtained by mixing at 0° C. with stirring at 0° C., and the mixture was refluxed for 40 minutes. After the reaction solution was returned to room temperature, it was poured onto ice and extracted with 200 ml of ethyl ether. The extracted ethyl ether was washed three times with brine and dried over anhydrous magnesium sulfate. After drying, it was filtered and the liquid was concentrated under reduced pressure to obtain 5.10 g (18.6 mmol) of a benzyl thioether compound.

5.10 g (18.6 mmol) of this benzyl thioether compound was dissolved in 30 ml of liquid ammonia at -78°C, 2.3 g (100 mmol) of metallic sodium pieces were added, and the mixture was stirred for 20 minutes. After increasing the reaction temperature and distilling off the ammonia, 20 ml of ethyl alcohol is added to dispose of the remaining sodium. Add another 100 ml of water and extract the solution with 200 ml of ethyl ether. The ethyl ether is washed three times with brine and then dried over anhydrous magnesium sulfate. After drying, filter and concentrate the liquid under reduced pressure to obtain 3.4 g (18.5 mmol) of the compound ().
(4,8-dimethyl-3,7-nonadiene-1-
thiol) was obtained. (97% yield for homogeraniol, 92.5% yield for compound ()),
The physicochemical data of the compound () is as follows.

Mass spectrum MSm/z184 (M ⁺ ) Infrared absorption spectrum (Cm ^-1 ) 1665 (C=C), 2550 (-SH) Nuclear magnetic resonance spectrum ( ¹ H nucleus, δ) 1.62 (2CH ₃ -), 1.68 (CH ₃ −) Nuclear magnetic resonance spectrum ( ¹³ C nucleus, δ) 16.3, 17.7, 24.9, 25.8, 26.8, 32.6, 40.0,
122.2, 124.4, 131.4, 137.7 [Example 2] 3.64 g (20 mmol) of the compound () was added to 50 ml of
Dissolved in THF and kept at -20℃ under stirring.
1.4 molar hexane solution of methyllithium, 28 ml
(20 mmol) and reacted at 0°C for 1 hour. Pour the reaction mixture onto ice and add 200% ethyl ether.
Extract in ml. The ethyl ether is washed three times with brine and then dried over anhydrous magnesium sulfate.
After drying, filter and concentrate the liquid under reduced pressure to give 3.02g.
(16.8 mmol) of geranyl methyl ketone was obtained. (Yield 84% based on compound ()).

Next, 3.02 g of lithium aluminum hydride was added to a solution of 1.0 g (26 mmol) suspended in 100 ml of ethyl ether while stirring under ice cooling.
(16.8 mmol) of geranyl methyl ketone is added dropwise. After the dropwise addition, the reaction mixture was allowed to react at 0° C. for 1 hour, and then the reaction solution was poured onto ice and extracted with 100 ml of ethyl ether. Ethyl ether was washed three times with brine and dried over anhydrous magnesium sulfate. After drying, filter and concentrate the liquid under reduced pressure to give 3.0g (16.5 mmol)
The corresponding 5,9-dimethyl-4,8-decadien-2-ol was obtained. (98% yield based on geranyl methyl ketone).

Below, 3.17 g (16 mmol) of compound (a) was converted from 3.0 g (16.5 mmol) of alcohol using exactly the same method as that used to convert homogeranyl alcohol to compound (a) shown in Example 1.
(5.9-dimethyl-4.8-decadiene-2-thiol) could be obtained. (Yield 97% based on alcohol, 80% yield based on compound ()) The physicochemical data of compound (a) were as follows.

Mass spectrum MS m/z 198 (M ⁺ ) Infrared absorption spectrum (cm ^-1 ) 1665 (C=C), 2550 (-SH) Nuclear magnetic resonance spectrum ( ¹ H nucleus, δ) 1.25 and 1.32 (CH ₃ -) , 1.60 (2CH ₃ −),
1.67 (CH ₃ −), nuclear magnetic resonance spectrum ( ¹³ C nucleus, δ) 16.2, 17.7, 24.5, 25.7, 26.6, 35.7, 39.4,
39.8, 121.6, 124.3, 131.1, 137.5.

[Example 3] 3.64 g (20 mmol) of compound () was added to 50 ml of
Dissolve in THF, add 28 ml (20 mmol) of a 1.4M hexane solution of n-butyllithium while stirring and maintaining the temperature at -20°C, and react at 0°C for 1 hour. Pour the reaction mixture onto ice and extract with 200 ml of ethyl ether. The ethyl ether is washed three times with brine and then dried over anhydrous magnesium sulfate. After drying, the filtrate was concentrated under reduced pressure.
4.04 g (18.2 mmol) of geranyl butyl ketone was obtained. (Yield 91% based on compound ()).

Following is 4.18 g (17.4 mmol) of compound (b) (8,12-dimethyl-7,
11-tridecadiene-5-thiol). (Yield 87% based on compound ()).

The physicochemical data of compound (b) were as follows.

Mass spectrum MS m/z 240 (M ⁺ ) Infrared absorption spectrum (cm ^-1 ) 1665 (C=C), 2550 (-SH) Nuclear magnetic resonance spectrum ( ¹ H nucleus, δ) 0.90 (broad, CH ₃ -) , 1.62 (2CH ₃ −) 1.68
( _CH3− ).

Nuclear magnetic resonance spectrum ( ¹³ C nucleus, δ) 14.0, 16.4, 17.7, 22.1, 25.7, 26.6, 29.5, 37.6, 37.7, 39.8, 41.4, 121.5, 124.3, 131.4, 137.7, [Effect] Compound of the present application () and ( ) is a compound useful as a synthetic intermediate for the aforementioned sulfur-containing bicyclic terpenoids () and (). In fact, if an acid catalyst is applied to compounds (), (a) and (b) to cause a cyclization reaction, the compounds (),
It was confirmed that (Va) and (Vb) were easily induced.

Claims (1)

[Claims] A compound represented by the following formula: (In the formula, R represents H or an alkyl group having 1 to 4 carbon atoms.)