JPH0316932B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the general formula () The present invention relates to a method for producing a 3-methyl-3-penten-1-ol derivative represented by: In the above formula, R ¹ represents a hydrogen atom or an R ³ CO- group. Here, R ₃ represents an organic group, such as methyl group, ethyl group, propyl group, butyl group, pentyl group, octyl group, undecyl group, pentadecyl group, heptadecyl group, cyclopentyl group, cyclohexyl group, 2-cyclohexyl group, etc. Alkyl group; vinyl group, 1-propenyl group, allyl group,
Alkenyl groups such as isopropenyl group, 2-methylallyl group, 1-butenyl group, 2-butenyl group, 1,3-butadienyl group; Aryl group such as phenyl group, tolyl group, xylyl group, naphthyl group, pyridyl group; benzyl group, 1-phenylethyl group, 2-phenylethyl group, 1-phenylpropyl group, 3-phenylpropyl group, 2-methyl-
Aralkyl groups such as 1-phenylpropyl group and 2-naphthylethyl group; alkoxyalkyl groups such as methoxymethyl group, ethoxymethyl group, propoxymethyl group, butoxymethyl group, ethoxyethyl group, cyclohexyloxymethyl group, menthoxymethyl group, etc. aryloxyalkyl groups such as phenoxymethyl group, 2-phenoxyethyl group, and naphthoxymethyl group; In the general formula (),
R ² is an alkyl group such as methyl group, ethyl group, propyl group, isobutyl group, 2-ethylhexyl group, 2,6-dimethylhebutyl group; vinyl group, 1-
Alkenyl groups such as methylpropenyl group, allyl group, 2,6-dimethyl-1,5-heptadienyl group; cycloalkyl groups such as cyclopropyl group, cyclopentyl group, cyclohexyl group, methylcyclohexyl group; cyclopentenyl group, cyclohexenyl group , cycloalkenyl groups such as methylcyclohexenyl group; aralkyl groups such as benzyl group, tolylmethyl group, and phenylethyl group; aryl groups such as phenyl group, tolyl group, xylyl group, isopropylphenyl group, t-butylphenyl group, and anisyl group. represent The 3-methyl-3-penten-1-ol derivative represented by the general formula () can be used as an auxiliary agent for modulating or enhancing the aroma of perfume components or other aroma components, and as an auxiliary agent for these aroma components or auxiliaries. It is useful as a synthetic intermediate for
und Kosmetik, 55. Jabrgang, 12/74; and JP-A-55-51014). Conventionally, 3-methyl-3-penten-1-ol derivatives have been produced by the following method (see the above-mentioned literature), but this method involves long steps and cannot be said to be an industrially advantageous method. (In the formula, Ph, Et, and Ac mean a phenyl group, an ethyl group, and an acetyl group, respectively.) The present inventors obtained 3-methyl-3-pentene-1- As a result of intensive research to develop a method for easily producing all derivatives, 4-methyl-5,6-dihydro-
General formula from 2H-pyran () (In the formula, R ³ is as defined above, and Q represents a halogen atom or R ⁴ COO- group.
R ⁴ is the same as or different from R ³ and represents an organic group. ) It was discovered that an alkene derivative represented by the following formula can be easily obtained, and that a 3-methyl-3-penten-1-ol derivative can be easily produced in good yield using this alkene derivative as a raw material, leading to the present invention. That is, according to the present invention, the general formula ()
An alkene derivative represented by the general formula () R ² -Mg-X ... () [wherein R ² has the same meaning as in the general formula (), and X represents a halogen atom. ] 3-methyl- represented by the general formula () by reacting with a Grignard reagent represented by
3-penten-1-ol derivatives can be produced. In addition, the alkene derivative represented by the general formula () is 4-methyl-5,6-dihydro-2H
-Pyran and general formula () [In the formula, R ³ and Q have the same meanings as in the general formula (). ] It can be easily obtained by reacting the acid derivative shown in the following in the presence of a Lewis acid. 4-Methyl-5,6-dihydro-2H-pyran used as a raw material is a large amount of by-product when producing isoprene from isobutene and formalin. It can also be synthesized by reaction, etc., and can be obtained easily and inexpensively. Examples of the Lewis acid used in the reaction between 4-methyl-5,6-dihydro-2H-pyran and the acid derivative represented by the general formula () include boron trifluoride,
Ether complex, aluminum chloride, aluminum bromide, ferrous chloride, ferric chloride, stannous chloride,
Examples include stannic chloride, zinc chloride, sulfuric acid, p-toluenesulfonic acid, etc., but preferred are zinc chloride, aluminum chloride, and boron trifluoride/ether complex. The amount of Lewis acid used is 4
-Methyl-5,6-dihydro-2H-pyran in a molar amount of 0.001 to 0.5 times, preferably 0.01 to 0.5 times. This reaction is preferably carried out in a solvent, such as hydrocarbon halides such as 1,2-dichloroethane, dichloromethane, chloroform, 1,1,2-trichloroethylene, carbon tetrachloride, chlorobenzene; benzene, toluene, xylene, Hydrocarbons such as cyclohexane, n-hexane, and ligroin; nitrogen-containing compounds such as nitromethane, nitrobenzene, benzonitrile, and acetonitrile; oxygen-containing compounds such as methyl ethyl ketone, acetic acid, ethyl acetate, and butyl acetate, or mixtures thereof can be used as the solvent. The amount of the solvent used is about 2 to 100 times, preferably about 5 to 20 times the weight of 4-methyl-5,6-dihydro-2H-pyran. This reaction is usually carried out at -5°C to 70°C, preferably at 0°C to 50°C. The reaction between the alkene derivative represented by the general formula () and the Grignard reagent represented by the general formula () is preferably carried out in a solvent. The solvent is preferably one that is inert to the Grignard reagent, and ether solvents such as tetrahydrofuran, diethyl ether, and diisopropyl ether are particularly preferred. The amount of the solvent to be used is about 1 to 100 times, preferably about 5 to 20 times the weight of the alkene derivative represented by the general formula (). The Grignard reagent represented by the general formula () is used in an amount of about 0.5 to 5 times, preferably 0.8 to 3.5 times, the amount of the alkene derivative represented by the general formula (). This reaction is usually carried out at -78°C to 70°C, preferably at -20°C to 30°C. Moreover, in order to carry out this reaction efficiently, it is preferable to carry out it in the presence of a catalyst. Examples of catalysts include copper halides such as copper chloride, copper bromide, and copper iodide; complex compounds of these copper halides such as dimethyl sulfide and tributylphosphine; and dilithiotetrachlorcupute (Li ₂ CuCl). _Four )
or nickel compounds such as nickel chloride, nickel bromide, nickel acetylacetonate, nickel bis(triphenylphosphine) chloride, nickel chloride [bis(diphenylphosphino)propane], etc. . In a preferred embodiment of the present invention, 4-methyl-5,6-dihydro-2H-pyran and Lewis acid are dissolved or suspended in a solvent, then an acid derivative represented by the general formula () is added, and about By continuing stirring for 0.5 to 4 hours, a reaction mixture containing an alkene derivative represented by the general formula () is obtained.
The alkene derivative represented by the general formula () is isolated from this reaction mixture, for example, by distillation.
Next, the alkene derivative represented by the general formula () and the catalyst are dissolved or suspended in a solvent, and while stirring and cooling under an inert gas atmosphere such as nitrogen, the alkene derivative represented by the general formula () is approximately 0.8 ~
A 3.5-fold molar amount of the Grignard reagent represented by the general formula () is added and reacted for about 0.5 to 8 hours. After adding the Grignard reagent represented by the general formula (), stirring is continued for about 0.5 to 4 hours to obtain 3-methyl-3- represented by the general formula ().
A reaction mixture containing a penten-1-ol derivative is obtained. 3-methyl-3 from this reaction mixture
The -penten-1-ol derivative can be separated and recovered by a conventional method. For example, after pouring the reaction mixture into an aqueous ammonium chloride solution,
This is extracted with diethyl ether, and the extract is washed with water and dried. Then, the solvent is distilled off from the extract to obtain a crude 3-methyl-3-penten-1-ol derivative. A highly pure 3-methyl-3-penten-1-ol derivative can be obtained by purifying this crude product by column chromatography, distillation, or the like. The present invention will be specifically described below with reference to Examples. Example 1 Under nitrogen atmosphere, 20 g of 1,5-diacetoxy-3-methyl-2-pentene, 0.25 g of lithium chloride,
Cupric chloride 0.40g and tetrahydrofuran 100ml
isobutylmagnesium bromide in a solution consisting of
200 ml of tetrahydrofuran containing 0.15 mol −20
It was added dropwise at ℃. After the dropwise addition, the temperature was raised to 0°C, and then the reaction solution was poured into an aqueous ammonium chloride solution, and this was extracted with diethyl ether. The extract was dried, concentrated, and purified by silica gel column chromatography to obtain 12.67 g of 3,7-dimethyl-3-octenyl acetate having the following NMR spectrum (yield: 67%). NMR spectrum (90MHz) δ ^HMS _CDCl3 : 0.83 (d, J=7Hz, 6H); 1.0-2.4 (m,
10H); 3.95-4.2 (m, 2H); 5.0-5.33 (m, 1H) Mix and dissolve 12.0 g of 3,7-dimethyl-3-octenyl acetate obtained in the above method with 100 ml of methanol and 30 ml of ethanol. A solution prepared by dissolving 7 g of potassium hydroxide in 70 ml of water was added to this solution, and the mixture was stirred at 40° C. for 2 hours. The reaction solution was concentrated under reduced pressure, water was added thereto, and the mixture was extracted with diethyl ether. The extract was washed with water, dried, concentrated, and distilled under reduced pressure to produce 3,7-dimethyl-3-octen-1-ol having the following physical properties.
8.39g was obtained (yield 88.7%). Boiling point: 63℃/0.7mmHg. NMR spectrum (90MHz) δ ^HMS _CDCl3 : 0.73-2.4 (m, 17H); 3.61 (t, J = 7Hz,
2H); 5.06-5.4 (m, 1H); Example 2 In Example 1, isobutylmagnesium bromide
Octyl Magnesium Bromide instead of 0.15mol
In the same manner as in Example 1 except that 0.15 mol was used, 18.40 g of 3-methyl-3-tridecenyl acetate having the following NMR spectrum was obtained (yield: 73%). NMR spectrum (90MHz) δ ^HMS _CDCl3 : 0.8-0.95 (m+3H); 1.22 (s, 14H); 1.6 (d, J=7Hz, 2H); 1.97 (s, 3H); 2.1-2.4 (m, 2H); 3.93-4.2 (m, 2H); 5.0-5.33 (m, 1H) 18 g of 3-methyl-3-tridecenyl acetate obtained by the above method was mixed with 200 ml of ethanol,
100ml methanol, 12g potassium hydroxide and 70ml water
ml and stirred at 40°C for 2 hours. After concentrating the reaction solution, water was added to it and extracted with diethyl ether. The extract was washed with water, dried, concentrated, and distilled under reduced pressure to obtain 3-3, which has the following physical properties.
12.71g of methyl-3-tridecen-1-ol
(yield 84.6%). Boiling point: 103-106℃/0.6mmHg. NMR spectrum (90MHz) δ ^HMS _CDCl3 : 0.68-2.4 (m, 25H); 3.61 (t, J = 7Hz,
2H); 5.1-5.41 (m, 1H) Example 3 1200g of acetic anhydride, 1250g of acetic acid and zinc chloride
392.6 g of 4-methyl-5,6-dihydro-2H-pyran was added dropwise to 163.5 g of the mixed solution while stirring at 40°C. After the dropwise addition, stirring was continued for 2 hours, and 229.5 g of sodium acetate was added while maintaining the liquid temperature at 40°C.
The reaction solution was stirred at room temperature overnight, poured into water, and extracted with diethyl ether. The extract was washed successively with water, an aqueous sodium bicarbonate solution, and brine, dried over magnesium sulfate, and concentrated. By distilling the concentrate under reduced pressure, 1, which has the following boiling point, is obtained.
5-diacetoxy-3-methyl-2-pentene
369.2g was obtained. Boiling point: 87-89℃/3mmHg Under nitrogen atmosphere, 1,5-diacetoxy-3-methyl-2-pentene 144g, lithium chloride 1.84g,
Tetrahydrofuran 2 containing 1 mol of phenylmagnesium bromide was added dropwise to a solution consisting of 3.03 g of cupric chloride and 1 mol of tetrahydrofuran under ice cooling.
After the dropwise addition, the reaction solution was stirred for 1 hour, poured into an aqueous ammonium chloride solution, and extracted with diethyl ether. The extract was dried, concentrated, and distilled under reduced pressure to obtain 3-methyl-5 having the following physical properties.
-Phenyl-3-pentenyl acetate 109.3g
was obtained (yield 64.9%). Boiling point: 102-105℃/1mmHg. NMR spectrum (90MHz) δ ^HMS _CDCl3 : 1.66-1.8 (m, 3H); 1.95, 1.97 (s,
3H);; 2.2-2.55 (m, 2H); 3.33 (d, J=7Hz,
2H); 4.14 (t, J=7Hz, 2H); 5.26-5.6 (m,
1H); 7.0-7.4 (m, 5H) 74g of 3-methyl-5-phenyl-3-pentenyl acetate obtained by the above method was added to a solution consisting of 35.4g of potassium hydroxide, 177ml of water and 200ml of ethanol, and the mixture was left overnight. After standing, the mixture was heated under reflux for 30 minutes. The reaction solution was concentrated under reduced pressure, water was added thereto, and the mixture was extracted with diethyl ether. Wash the extract with water,
After drying, the mixture was concentrated and distilled under reduced pressure to obtain 36.1 g of 3-methyl-5-phenyl-3-penten-1-ol having the following physical properties (yield: 59.5%). Boiling point: 101-103℃/1.5mmHg. NMR spectrum (90MHz) δ ^HMS _CDCl3 : 1.57-1.77 (m, 4H); 2.13-2.5 (m, 2H); 3.34 (d, J = 7Hz, 2H); 3.53-3.76 (m,
2H); 5.3-5.6 (m, 1H); 7.0-7.4 (m, 5H) 18 g of 3-methyl-5-phenyl-3-penten-1-ol obtained by the above method was dissolved in 200 ml of hexane, 0.9 g of 5% Pd/C was added to this solution and stirred under a pressure of about 6 kg of hydrogen. After the reaction is completed, the catalyst is separated, the reaction solution is concentrated, and then distilled under reduced pressure to obtain 3-
Methyl-5-phenylpentan-1-ol
36.1g was obtained (yield 59.5%). Boiling point: 98.5-105℃/1.5mmHg. NMR spectrum (90MHz) δ ^HMS _CDCl3 : 1.9 (d, J=6Hz, 3H); 1.2-1.8 (m,
6H); 2.4-2.8 (m, 2H); 3.63 (t, J=6Hz,
2H); 7.0-7.4 (m, 5H) Examples 4-14 4-Methyl-5,6-dihydro-2H-pyran
300 g of zinc chloride, and 1.5 g of 1,2-dichloroethane, 218 ml of acetyl chloride was added dropwise while stirring at room temperature. After the dropwise addition, stirring was continued for 1 hour, and the resulting reaction solution was poured into water, and extracted with diethyl ether. The extract was washed successively with water, an aqueous sodium bicarbonate solution, and brine, dried over anhydrous magnesium sulfate, and then concentrated. The obtained concentrate was distilled under reduced pressure to obtain 221 g of 5-chloro-3-methyl-3-penten-1-yl acetate having the boiling point shown below. Boiling point: 62-75℃/1mmHg. 5-chloro-3-methyl-3- under nitrogen atmosphere
A solution of 5 mmol of phenylmagnesium bromide in 10 ml of tetrahydrofuran was added dropwise at 0° C. to a solution of 3 ml of tetrahydrofuran containing 5 mmol of pentenyl acetate and 0.1 mmol of the catalyst shown in Table 1. After the dropwise addition, the mixture was stirred at 0°C for 1 hour. The resulting reaction solution was poured into an aqueous ammonium chloride solution and extracted with diethyl ether. The extract was dried, concentrated, and purified by silica gel column chromatography to obtain 3-methyl-5-phenyl-3-pentene-
1-yl acetate was obtained. The results are shown in Table 1.

[Table] In the table, Me, Bu, Ph, acac, and dppp mean a methyl group, a butyl group, a phenyl group, an acetylacetonate group, and 1,3-bis(diphenylphosphino)propane, respectively. Example 15 5-chloro-3-methyl-3- under nitrogen atmosphere
Phenylmagnesium bromide in a solution of 5 mmol of pentenyl acetate in 5 ml of tetrahydrofuran.
A 40 ml solution of 20 mmol of tetrahydrofuran was added dropwise at 0°C. After the addition, the mixture was stirred at room temperature for 1 hour. Pour the obtained reaction solution into an aqueous ammonium chloride solution,
Extracted with diethyl ether. The extract was dried, concentrated, and purified by silica gel column chromatography to obtain 3-methyl-5-phenyl-
0.63g of 3-penten-1-ol was obtained (70.8
%). Examples 16-26 Under nitrogen atmosphere, with 5 mmol of alkene derivative
5 ml of tetrahydrofuran containing 0.1 mmol of Li ₂ CuCl ₄
The Grignard reagent shown in Table 2 was added dropwise to the solution at 0°C. After the addition, the mixture was stirred at room temperature for 1 hour. The resulting reaction solution was poured into an aqueous ammonium chloride solution and extracted with diethyl ether. The extract was dried, concentrated, and purified by silica gel column chromatography to obtain a 3-methyl-3-penten-1-ol derivative in the yield shown in Table 2.

【table】

[Table] In the table, Ph, Bu ⁿ and ^But are phenyl groups and n-
It means a butyl group or a t-butyl group.

Claims (1)

[Claims] 1. General formula (In the formula, R ³ represents an organic group, and Q represents a halogen atom or R ⁴ COO- group. Here, R ⁴ is the same as or different from R ³ and represents an organic group.) A Grignard reagent represented by the formula R ² -Mg-X (wherein R ² represents an alkyl group, alkenyl group, cycloalkyl group, cycloalkenyl group, aralkyl group or aryl group, and X represents a halogen atom); A general formula characterized by the reaction of (In the formula, R ¹ represents a hydrogen atom or R ³ CO- group, and R ² and R ³ are as defined above.) Method for producing a 3-methyl-3-penten-1-ol derivative represented by . 2 4-Methyl-5,6-dihydro-2H-pyran and general formula (In the formula, R ³ represents an organic group, and Q represents a halogen atom or R ⁴ COO- group. Here, R ⁴ is the same as or different from R ³ and represents an organic group.) By reacting in the presence of Lewis acid, the general formula (In the ^formula , R ³ and Q are as defined above.) ^An alkene derivative represented by , a cycloalkyl group, a cycloalkenyl group, an aralkyl group, or an aryl group, and X represents a halogen atom). (In the formula, R ¹ represents a hydrogen atom or R ³ CO- group, and R ² and R ³ are as defined above.) Method for producing a 3-methyl-3-penten-1-ol derivative represented by .