JPS63122691A - Production of bicyclooctene compound - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful for perfume, etc., without forming by-product in high yield advantageously in an industrial scale, by subjecting a specific olefinic compound to addition reaction with a specific diene compound in the presence of a nonhydrogen ion type Lewis acid. CONSTITUTION:A compound expressed by formula I [R<1> and R<2> are H or 1-5C aliphatic hydrocarbon; A is H, halogen, etc.; Y is formula II (R<5> is R<1>), NO2, etc.] is subjected to addition reaction with a diene compound expressed by formula III (R<9>-R<11> is each 1-5C alkyl) in the presence of nonhydrogen ion type Lewis acid (e.g. tetrachlorotitanium, etc.), preferably at -10-50 deg.C for 1-10hr to provide the aimed compound expressed by formula IV. The compound expressed by formula I includes acrolein, etc., and the compound expressed by formula II includes 1-trimethylsiloxy-3,5,5-trimethyl-1,3-cyclohexadiene, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a method for producing a bicyclooctene compound, which is useful as a fragrance per se, and is also valuable as a gayonone derivative, an intermediate for pharmaceutical synthesis, and the like.

[Conventional technology]

As a conventional method for producing a bicyclooctene compound represented by the general formula (3) described below, a method for producing it from inphorone silyl enol ether and methyl vinyl ketone according to the following formula has been reported in JP-A-57-80391. .

SIMel In this method, the reaction is carried out under pressure at a high temperature of 200° C. for a long time of 15 hours. Therefore, it has the disadvantage that side reactions such as polymerization of methyl vinyl ketone, which is unstable to heat, occur and by-products that are difficult to separate are produced, and are not suitable for industrial implementation.

[Problem that the invention seeks to solve]

An object of the present invention is to overcome the disadvantages or defects of the prior art as described above and to provide an industrially advantageous method for producing the entire bicyclooctene compound represented by the general formula (3).

[Means for solving problems]

The present invention is based on the general formula (1) (where R1 and R2 represent a hydrogen atom or an aliphatic hydrocarbon group having 1 to 5 carbon atoms, and A is a hydrogen atom, an aliphatic hydrocarbon group having 1 to 5 carbon atoms, or a halogen atom. , -〇R3 or -〇
C-R', R3 is a hydrocarbon group having 1 to 5 carbon atoms, a phenyl group, or -CNR'R', -C=Ns-8O2P
h, -So2PhMs or -NO2, R5,,R
8 represents a hydrogen atom or an aliphatic hydrocarbon group having 1 to 5 carbon atoms) and an olefinic compound represented by the general formula (2) (wherein R9, RID, and R11 represent an alkyl group having 1 to 5 carbon atoms) The general formula (3) is characterized by carrying out an addition reaction with a diene compound represented by the formula (3) in the presence of a non-hydrogen ion type Lewis acid (wherein R", R2, R"-
R11, A and Y are the methods for producing the bicyclooctene compound shown in the above).

Compared to conventional methods, the method of the present invention allows the reaction to be carried out at low temperatures around room temperature, under normal pressure, and in a short time, thereby suppressing the polymerization of methyl vinyl ketone and side reactions, thereby preventing the formation of by-products that are difficult to separate. First, bicyclooctene compounds can be produced industrially and advantageously in high yields.

The olefinic compound used in the method of the present invention has the general formula (
Although essentially any compound can be used as long as it satisfies 1), alkyl groups such as methyl, ethyl, propyl, butyl, and pentyl are usually used as the aliphatic hydrocarbon group in the general formula. Specific examples of such olefinic compounds include α,ρ unsaturated aldehydes such as acrolein, methacrolein, 2-pentenal, and 2-hexenal, 3-buten-2-one, 1-penten-3-
1-hexen-3-one, 1-hebuten-3-one, 1-octen-3-one, 3-methyl-3-buten-2-one, 3-bromo-3-buten-2-one , 3-
Methoxy-3-buten-2-one, 3-ethoxy-3-
Buten-2-one, 3-trimethylsilyloxy-3-
Buten-2-one, 3-acetoxy-3-buten-2-
α, β unsaturated ketones such as on, acrylic acid methyl ester, acrylic acid ethyl ester, acrylic acid propyl ester, acrylic acid butyl ester, methacrylic acid methyl ester, α-chloro-acrylic acid methyl ester Unsaturated esters, as well as acrylonitrile, α-chloroacrylonitrile, α-acetoxyacrylonitrile, acrylamide, N,N-dimethylacrylamide, N,N-diethylacrylamide, nitroethylene, p-)luenesulfonylethylene, benzenesulfonylethylene, etc. can be exemplified.

The diene of general formula (2) is inphoron with a catalytic amount of iron chloride (
(J, Am,
Cham, Soc.

106.7619-7621 (1984): 1 etc.

The addition reaction of the present invention is carried out by reacting these olefinic compounds (1) and diene compounds (2) in the presence of non-hydrogen ion type Lewis.

As the Lewis acid that can be used in the present invention, essentially any acid that can accept electrons without releasing hydrogen ions (hereinafter referred to as a non-hydrogen ion type Lewis acid) can be used. A further explanation of non-hydrogen ion type Lewis acids is the theory of acids and bases based on the transfer of electrons proposed by G. At that time, the other party dissociates and the one that covalently bonds with a part of it is the base, and the other party that accepts electrons is the acid.From this, acids and bases are electron acceptors that accept electron pairs, and electron acceptors that accept electron pairs. It means an acid obtained by removing hydrogen ions from an acid defined as an electron donor that provides a pair. Examples of such non-hydrogen ion type Lewis acids include zinc chloride, zinc bromide, zinc iodide, and zinc chloride. Ditin, titanium tetrachloride, aluminum chloride, aluminum bromide, boron trifluoride diethyl ether complex, boron trifluoride acetic acid complex, copper borofluoride, cupric chloride, cupric bromide, copper complex acetate, magnesium chloride , magnesium bromide, gallium chloride, antimony pentachloride, dimethylaluminum chloride, diethylaluminum chloride/ethylaluminum dichloride, etc.The reaction can be carried out at normal pressure or under increased pressure.The reaction temperature is -40 -
100°C, especially -10 to 50°C is preferred. The reaction can be carried out in the presence or absence of a solvent. Reaction solvents include hydrocarbon solvents such as hexane, benzene, toluene, and xylene, ethereal solvents such as diethyl ether, dibutyl ether, tetrahydrofuran, diimbutyl ether, dioxane, mono- or diethylene glycol dimethyl ether, mono- or diethylene glycol diethyl ether, and tetrahydropyran. ,
Examples include halogenated solvents such as monochloroethane, dichloromethane, chloroform, carbon tetrachloride, and 1,2-dichloroethane, and mixed solvents consisting of arbitrary combinations thereof.

The amount of the olefinic compound of general formula (1) to be used is preferably 0.1 to 10 times, particularly 0.8 to 2 times, mole per mole of the diene compound of general formula (2). The amount of Lewis acid used is 0.01 to 0.01 to the diene compound of general formula (2).
It is preferably 5 times the mole, particularly 0.05 to 1 times the mole. If the selectivity of the reaction is not affected, the entire reaction can be carried out at other molar ratios. Reaction time is 0.05-4
8 hours, especially 1 to 10 hours is preferred.

After the reaction is complete, the reaction solution is poured into a large excess of a basic solution such as aqueous sodium bicarbonate, potassium carbonate, or sodium carbonate to make the reaction system basic, and then a suitable extraction solvent such as benzene, toluene, or tetrachloride is added. After extracting with carbon, chloroform, ethyl acetate, etc., collecting the solvent layer, washing with saturated saline, neutralizing, drying with, for example, sodium sulfate, and recovering the solvent by distillation, the general formula (3) is obtained. A bicyclooctene compound represented by can be obtained. The bicyclooctene compound can be purified by vacuum distillation, column chromatography, or the like, if necessary.

Hereinafter, the present invention will be specifically explained with reference to Examples.

Example 1゜1-trimethylsiloxy-3,5,5-trimethyl-1
,3-cyclohexadiene 477.2y9 (2,,2
7 mmol), 3-buty/-2-one 1 B 3. O
After dissolving q (2 [1 mmol)] in dichloromethane 5-, anhydrous zinc bromide 451H1 (0.2 mmol) was added at 25°C and stirred at the same temperature for 3 hours and 45 minutes. Next, a saturated aqueous sodium bicarbonate solution (15-) was added, followed by extraction with (100-) ethyl acetate and washing with saturated brine. After drying over anhydrous magnesium sulfate and recovering ethyl acetate, a fraction of 53Z9q was obtained by simple distillation under reduced pressure. This fraction was purified by gas chromatography (PEt 20M, 70°~2
As a result of analysis at 00℃1m), 7-acetyl-3,5,
5-)! J Methyl-1-trimethylsiloxybicyclo(
It contained 79.2% and 10.5% of the endo-isomer (a) and echyne-isomer (b) of 2,2,2) oct-2-ene, respectively. The ciendo form (a) and the echin form (b) were isolated by silica gel chromatography.

End body (!L) IR: (neat) 3060. 1715, 126
0, 1110.890, 850, 760 m-' NMR: (δTMS ppm in CDCl3) 0
．． 13 (s, 9H) 0.83 (s, 3H)
1.03 (s, 3H) 1.37 (brs, 2H)
1.67-2. ．． 03(m, 3H) 1.82(
d, J=2Hz, 3H) 2. ,lo(a,3H)
2.60-3.00 (m, IH) 5.57 (
brs, IH) MS: m/e 280 (M”,
2) Echin body (b) IR: (neat) 3050, 1710, 125
8, 1110.880, 842, 760 cm-” NMR: (δTMS ppm in CDCl3) 0
．． 10 (s, 9H) 0.98 (a, 3H)
1.18 (s, 3H) 1.08-1.43 (m, 2H
) 1.45-1.73 (m, 2H) 1.75 (d,
J=2Hz, 3H) 1.97~2.40(m, IH
)2.22(s, 3H)! 40-2.97 (m, L
H) 5.77 (brs, IH) MS: m/e 280 (M”, 1) Example 2 1-trimethylsiloxy-3,5,5-trimethyl-1
,3-cyclohexadiene 562'4W (2,39m
mol), 3-butene-2-oni/183.0η
After dissolving (2,61 Masazono 1) in toluene, 55 μm (0,39 mmol) of boron trifluoride etherate was added at 0° C. and stirred at the same temperature for 2 hours.

Next, add 15 g of a saturated aqueous solution of sodium hydrogen carbonate, extract with 100 g of ethyl acetate, and wash with saturated brine. After drying over anhydrous magnesium sulfate and recovering ethyl acetate, a fraction of 531.41M1 was obtained by simple distillation under reduced pressure. As a result of gas chromatography analysis of this fraction, the endo-isomer (a) and ekyne-isomer (b) of 7-acetyl-λ5.5-trimethyl-1-trimethylsiloxybicyclo[2λ2]oct-2-ene were found to be 81% each. .0chi,
It contained 10.8 inches.

Example 3 1-trimethylsiloxy-3,5,5-)dimethyl-1
, 3-cyclohexadiene 466.0g (122mm
ol), acrolein 158.0q (182mmo
l) After dissolving in 5-t-dichloromethane, 60 μm (0.27 mmol) of anhydrous zinc bromide was added at 5°C, and 2
Stir at 5°C for 5 hours and 30 minutes. Next, a saturated aqueous sodium bicarbonate solution 15- is added, followed by extraction with 150-ethyl acetate and washing with saturated brine. After drying with anhydrous magnesium sulfate and recovering ethyl acetate, perform simple distillation under reduced pressure! 7
A 492.2jv fraction was obtained. Analysis of this fraction by gas chromatography revealed that 7-formyl-3,5,5-1
Limethyl-1-trimethylsiloxybicyclo[2,12
] Oct-2-ene endo isomer (c), echin isomer (d)
'I contained 66.2% and 9.0%, respectively. The υ endo form (e) and the echin form (d)'e were isolated by silica gel chromatography.

End body (c) IR: (neat) 3050, 1730, 111
5,845m-”NMR: (δ TMS ppm in
CDCl3) 0.15 (s, 9H) 0.8
5 (s, 3H) 1.05 (s, 3H)1.
4 (d, 2H) 1.27-1.63 (m, 2
H) 1.78 (d.

J=2Hz, 3H) 1.86~2.67 (m, 2
H) 5.67 (brs, IH) 9.47 (d,
J=3Hz, IH)MS: m/e 296(M”,
1) Echin body (d) IR: (neat) 3060. 1730. 1
260, 11o5.880, 850z-” NMR: (δTMS ppm in CDCIg) 0
．． 17 (s, 9H) 0.83 (m13H) 1.
00 (s, 3H) 1.07-1.67 (m, 4H)
1.77 (d, J = 2Hz, 3H) 213-137 (m
, IH) 137-2.60 (m11H) 5.80 (
brs, IH) 10.0(s, IH) M S:
m/a 296 (M'', 1) Example 4 1-trimethylsiloxy-3,5,5-)dimethyl-1
, 3-cyclohexadiene 452.0! ? (2,15
mmol), Akron Inn 15 ZI! (2,71
mmol) in dichloromethane, 25.5 μm of boron trifluoride etherate (0.18 mmol
)′! Add 1 liter at -6°C and stir at the same temperature for 2 hours.

Next, after adding saturated aqueous sodium hydrogen carbonate solution 15-,
Extract with 150 ml of ethyl acetate and wash with saturated brine. After drying over anhydrous magnesium sulfate and recovering ethyl acetate, a fraction of 453.3 ml was obtained by simple distillation under reduced pressure.

As a result of analyzing this fraction by gas chromatography, 7
-Formyl-3,5,5-trimethyl-1-trimethylsiloxyloxy-[:ZZ2]]63.
It contained 0% and 7.2%.

Example 5 1-trimethylsiloxy-3,5,5-)dimethyl-1
, 3-cyclohexadiene 463. lrItg(2,2
0 mmol), acrylic acid methyl ester 220.
After dissolving O (2,56 mmol) in dichloromethane, 120 ■ (0,54 mmol) of anhydrous zinc bromide was dissolved.
) was added at 25°C and stirred at the same temperature for 5 hours and 30 minutes.

Then saturated hydrogen carbonate) IJum aqueous solution 15m/! After addition, the mixture is extracted with 200-ethyl acetate and washed with saturated brine.

After drying over anhydrous magnesium sulfate and recovering ethyl acetate, a fraction of 575.7 ml was obtained by simple distillation under reduced pressure. Analysis of this fraction by gas chromatography revealed that 7-medoxycarbonyl-3.5.5-trimethyl-1-trimethylsiloxybicyclo[Z2.2]oct-2-ene was endo-isomer (e), ekyne-isomer ( fLa - 79 each
．． It contained 6% and 5.5%. By silica gel chromatography, Ciendo Zhu e) and Echin body (F)'
e isolated.

End body (e) I R: (neat) 3060.1745.16
60.1260.1220.1172.1120.85
-1HMR of 0: (δTMS, ppm in CD
Cl5 ) 0.13 (s, 9H) 0.83 (s,
3H) 1.02 (s, 3H) 1.33 (brs,
2I() 1.33-1.77 (m, 2H)
1.83 (d, J=2Hz, 3H) 100-28
3 (m, 2H) 3.60 (s, 3H) 5.65
(brs, IH) MS: rn/e 296 (M”
, 2) Echin body (f) I R: (naat) 1740, 1650, 12
08, 1160.880, 846 Note 1 NMR: (δ TMS ppm in CDCIg
)0.11 (s, 9H) 0.83 (s, 3H)
1.18 (s, 3H) 0.90-1.50 (m, 2H
) 1.75 (d, 3H) 1.60~Z63 (
m, 4H) 3.60 (a, 3H) 5.80
(m, IH) MS: m/e 296 (M", l) Example 6 1-trimethylsiloxy-3,5,5-trimethyl-1
,3-cyclohexadiene 490.3wI (Z33 m
mol), acrylic acid methyl ester 240.2q
(Z79 mmol) k) Luene 5I117!
Boron trifluoride etherate 101”?
(0.71 rnmol) was added at -7°C, and the mixture was stirred at the same temperature for 4 hours. Next, 15-liters of saturated sodium bicarbonate was added, followed by extraction with 200-liters of ethyl acetate, and the mixture was washed with saturated brine. After drying over anhydrous magnesium sulfate and recovering ethyl acetate, a fraction of 555.7 cm was obtained by simple distillation under reduced pressure. As a result of gas chromatography analysis of the fraction with
It contained 84.7% and 2.8% of endo-isomer (e) and echyne-isomer (f) of oct-2-ene, respectively.

Example 7 1-trimethylsiloxy-tortoise5.5-trimethyl-1.
3-cyclohexadiene 510.3+q (2,43m
mol), acrylic acid methyl ester 247.9q
(2,88 mmol) in benzene 7rR1, anhydrous stannic chloride 1109 (0,38 mmol
) was added at 5°C and stirred at the same temperature for 5 hours. Next, 15 d of saturated sodium bicarbonate is added, followed by extraction with 200-ethyl acetate and washing with saturated brine. After drying over anhydrous magnesium sulfate and recovering ethyl acetate, a fraction of 507.5fi7 was obtained by simple distillation under reduced pressure. Analysis of this fraction by gas chromatography revealed that the endo-isomer (e
) and echin bodies (fee) were 79.5% and 5.4%, respectively.

Example 8 1-trimethylsiloxy-3,5,5-trimethyl-1
, 3-cyclohexadiene 477.9■ (2,27mm
ol), acrylonitrile 143.0■ (Z70 mm
After dissolving Zinc Bromide 2081F (0.92 mmol) in dichloromethane 5-, anhydrous zinc bromide 2081F (0.92 mmol) was added at 25° C. and the solution was pressed for 8 hours at the same temperature. Next, 15-ml of a saturated aqueous sodium bicarbonate solution was added, followed by extraction with 2001 nt of ethyl acetate and washing with saturated brine. After drying over anhydrous magnesium sulfate and recovering ethyl acetate, a fraction of 519.2 ml was obtained by simple distillation under reduced pressure. Analysis of this fraction by gas chromatography resulted in 7-Dia2 3.5.5-
) dimethyl-1-trimethylsiloxybicyclo(112
:]] Octo2-e endo body (e), Echin body (f
) contained 28.6% and 35.9%, respectively. Ciendo form (e) and echin form (f)e were isolated by silica gel chromatography.

End body (e) I R: (neat) 3060, 2250, 16
55, 1259.1120, 891.842, 760c
! n-n-1N: (δ TMs ppm in CD
Cl5 ) 0.17 (s, 9H) 0.86 (s
, 3H) 1.02 (s, 3H) 1.33 (s
, 2H) 1.27-1.67 (m, IH)
1.75-1.83 (m, HI) 1.83
(d, J=2Hz, 3H)2107~Z83 (m
, 2H) 5.82 (brs, 1■()MS:m
/a 263 (M”, 1) Echin body (fJ IR: (neat) 3060, 2250, 1660,
1258.1120, 880, 848 cm-' NMR: (δ TMS ppm in CDCl3
) 0.18 (s, 9H) 0.85 (a, 3) 1)
1.15 (a, 3H) 1.30-1.67 (m, 2H
) 1.75 (d, J=2Hz, 3H) 1.80~Z
63 (m, 4H) 5.65 (brs, IH) MS
: m/e 263 (M", 1) Example 9 1-trimethylsiloxy-3,5,5-trimethyl-1
, 3-cyclohexadiene 482. ．． 5TNi(2,3
0 mmol), acrylonitrile 155.5q (2,
70 mmol ) '(-dichloromethane 5-, then anhydrous aluminum chloride 55 m9 (0,41 mmol
l) Add at f-6°C and stir at the same temperature for 7 hours. Next, after adding 15 tIt of saturated aqueous sodium hydrogen carbonate solution, 2
Extract with 00rd ethyl acetate and wash with saturated brine. After drying over anhydrous image plane magnesium and recovering ethyl acetate, a fraction of 523.4 square meters was obtained by simple distillation under reduced pressure.

As a result of analyzing the fraction with gas chromatography, 7
- 29.0% each for the endo form (,) and the echyne form (f)' of 5-trimethyl-1-trimethylsiloxybicyclo(2,2,2)oct-2-ene,
Example 10 containing 34.4% 1-trimethylsiloxy-3,5,5-)dimethyl-1
,3-cyclohexadiene 47 i, sq (2,24
mmol), α-chloroacrylonitrile 519.4
After dissolving (5.97 mmol) in 5 tnl of dichloromethane, 170 Trq (0.75 mmol) of anhydrous zinc bromide
ol) at 25°C and stirred at the same temperature for 2 hours.

Next, after adding saturated aqueous sodium hydrogen carbonate solution 15-
Extract with ethyl vinegar and wash with saturated saline.

After drying with anhydrous magnesium sulfate and recovering ethyl acetate,
By distilling under reduced pressure, a fraction of 9600.1wi was obtained. Results of analyzing this fraction by gas chromatography 7
-Chlo0-7-diatu3.5.5-trimethyl-1-
trimethyl70xybicyclo(2,2,,2)octo-
The endo isomer (g) and the echin isomer (h) of 2-ene are each 33. i, 49. It contained lJ gold. Endo-isomer (g) and echin-isomer (h)' were determined by silica gel chromatography.
isolated.

End body (g) I R: (neat) 3060, 2250, 16
60, 1260.1130, 850 cm-' NMR: (δ TMS ppm in CDCl3
)0.21 (s, 9H) 0.90 (a, 3I
I) 1.13 (a, 3H) 1.33-2.50
(m, 5)ri 1.68 (d, J=2Hz,
3H) 5.78 (brs, IH) MS: m/e 282 (M”-Me, 5) Echin body (
h) IR: (neat)3070, 2250, 1660,
1260.1130, 950, 850c*-” NMR: (δ TMS ppm in CDCl3
) 0.22 (!l, 9H) 0.90 (s, 3
H) 1.13 (a, 3H) 1.33-3.10 (m
, 5H) 1.83 (d, J=2Hz, 3H) 5.6
7 (brs, IH) MS: m/e 282 (M''-Me, 5).

Claims (1)

[Claims] General formula (1) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (1) (However, in the formula, R^1 and R^2 are hydrogen atoms or aliphatic hydrocarbons having 1 to 5 carbon atoms. group, A is a hydrogen atom or an aliphatic hydrocarbon group having 1 to 5 carbon atoms, a halogen atom, -O
Indicates R^3 or ▲There are mathematical formulas, chemical formulas, tables, etc.▼,
R^3 represents a hydrocarbon group having 1 to 5 carbon atoms, a phenyl group, or a trimethylsilyl group, R^4 represents an aliphatic hydrocarbon group having 1 to 5 carbon atoms, and Y represents ▲mathematical formula, chemical formula, table, etc. There are ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, -C≡N, -SO_2
Ph, -SO_2PhMe or -NO_2, R^
5 to R^8 represent a hydrogen atom or an aliphatic hydrocarbon group having 1 to 5 carbon atoms. ) and the general formula (2) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(2) (However, in the formula, R^9 to R^1^1 represent an alkyl group having 1 to 5 carbon atoms. The general formula (3) is characterized by an addition reaction with a diene compound represented by (shown) in the presence of a non-hydrogen ion type Lewis acid.
) (However, in the formula, R^1, R^2, R^9 to R^1^1, A and Y are as described above.) A method for producing a bicyclooctene compound.