JPH0336810B2 - - Google Patents

Description

[Detailed description of the invention]

Object of the invention Industrial application field The present invention relates to 1,3-diene, 1,3-diol,
This invention relates to an improved method for producing homoallyl alcohol derivatives useful as intermediates for producing 1,4-diols, 1,4-diketones, furan derivatives, etc. Prior Art and Problems A divalent tin compound such as tin metal or stannous chloride is reacted with allyl bromide or allyl iodide to produce a diallyltin compound or a monoallyltin compound, which is reacted with a carbonyl compound and water and/or Homoallyl alcohol derivatives can be produced in good yields by reacting in an organic solvent such as tetrahydrofuran (THF) or ethers in the presence or absence of a proton donor such as a lower alkanol such as methanol or ethanol. is publicly known. Moreover, in this case, the homoallyl alcohol derivative can be produced by a one-step reaction method in which a divalent tin compound such as metal tin or stannous chloride is reacted with allyl bromide or allyl iodide and a carbonyl compound in a THF solvent. is known [“Chem.Lett.” 1507-1510 (1980) and “Chem.
Lett.”1527-1528 (1981)]. Homoallylic alcohol derivatives were also produced using a one-step reaction method in which metal tin, allyl bromide, and a carbonyl compound were reacted in the presence or absence of metal aluminum in aqueous ether. It is also known that it can be carried out [“Organomettallics” 2 , 191~
193 (1983)]. In the above method for producing homoallylic alcohol derivatives using metal tin or a divalent tin compound, in reality, a stoichiometric amount or more of metal tin, which is 1 mole or more per 1 mole of the starting carbonyl compound, is present in the reaction system. Or it is necessary to charge a divalent tin compound,
Large amounts of expensive metal tin or divalent tin compounds must be used. In addition, the above method is applicable only to allyl bromide or allyl iodide, which exhibits high reactivity to tin metal or divalent tin compounds and easily forms allyl tin compounds as the allyl halide used as a reactant. Allyl chloride, which is inexpensive, cannot be used because of its low reactivity. For these reasons, the method for producing homoallyl alcohol derivatives described above is not advantageous as an industrial production method. Therefore, there is a need for the development of a novel method for producing homoallylic alcohol derivatives that requires less use of expensive tin compounds and can be applied to inexpensive allyl chloride. The present invention provides a new method for producing homoallyl alcohol derivatives that meets these needs. Means for Solving the Constituent Problems of the Invention The present inventors have studied various methods in order to find a method that meets the above objectives, and as a result, they have arrived at the present invention. That is, the first aspect of the present invention provides a method for treating the general formula () in an organic solvent containing a proton donor. [In the formula, R ₁ and R ₂ each represent a hydrogen atom, an alkyl group, a cycloalkyl group, an aralkyl group, an aryl group, an alkynyl group, or an alkenyl group,
or R ₁ and R ₂ jointly represent one cycloalkyl group] and a carbonyl compound represented by the general formula () [In the formula, R ₃ , R ₄ , R ₅ , R ₆ and R ₇ each represent a hydrogen atom, an alkyl group, a cycloalkyl group, an aralkyl group, an aryl group, an alkynyl group, or an alkenyl group, or R ₃ and R ₅ , R ₃ and R ₆ , R ₅ and
R ₆ , R ₆ and R ₇ jointly represent one cycloalkyl group, and X represents a halogen atom] and metal aluminum are combined with metal tin and/or divalent tin. The general formula (
a) and/or (b) [In the formula, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , and R ₇ each have the above-mentioned meanings.] Actions and Effects According to the method of the present invention, allyl halides including allyl chlorides can be used. Furthermore, by using inexpensive metal aluminum as an activator, the amount of expensive metal tin and/or divalent tin compound and/or tetravalent tin compound used can be reduced to below stoichiometric amounts. Therefore,
Homoallylic alcohol derivatives can be produced at lower cost and in higher yields than conventional methods. Method of carrying out the invention Examples of the carbonyl compound of the general formula () used in the present invention include aldehydes; for example, formaldehyde, acetaldehyde, propylaldehyde, isopropylaldehyde, hexylaldehyde, crotonaldehyde, acrylaldehyde, methacrylaldehyde, citral, benzaldehyde , helotropin, and the like; examples include cyclohexanone, 2-methylcyclohexanone, acetone, butylmethylketone, acetophenone, benzylmethylketone, phenethylmethylketone, and the like. Also, carbonyl compounds having various functional groups (e.g. hydroxyl group) that cannot be used in the Grignard reaction; e.g. hydroxyketones,
Ketoesters, ketocarboxylic acids, haloketones, haloaldehydes can also be used. The carbonyl compound is used in a proportion of 0.1 to 10 moles per mole of the allyl halide compound of general formula (). Also, the formula of the general formula () in allyl halides used in the present invention

Examples of the moiety represented by the formula include alkenyl groups such as allyl group, methallyl group, crotyl group, prenyl group, α,α-dimethylallyl group, and cinnamyl group. In addition, the proton donors used in the present invention include water; lower alcohols such as methanol and ethanol; lower alkanoic acids such as acetic acid, formic acid, butyric acid; sulfonic acids such as p-toluenesulfonic acid and methanesulfonic acid; and sulfuric acid, Inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, and phosphoric acid can be used alone or in combination. Solvents used in the present invention include alcohols such as methanol, ethanol, propanol, and butanol, ethers such as diethyl ether, tetrahydrofuran, monoglyme, and diglyme, cellosolves such as methyl cellosolve and ethyl cellosolve, acetic acid, and propionic acid. , fatty acids such as butyric acid, esters such as ethyl acetate, ethyl formate, diethyl carbonate, aliphatic or aromatic hydrocarbons such as n-hexane, benzene, toluene, acetonitrile, propionitrile,
Examples include nitriles such as, halogenated hydrocarbons such as methylene chloride, dichloroethane, and chloroform, dimethylformamide, and dimethyl sulfoxide. When using solvents, they can be used alone or in combination. There is no particular restriction on the amount of solvent used, but in general, it is 0.01 to 1 mole of the carbonyl compound of general formula ().
-10, preferably 0.1-1. Furthermore, the less reactive carbonyl compound of general formula () can be activated by adding an acid to a reaction mixture consisting of the carbonyl compound of general formula (), the allyl halide of general formula (), and a reaction medium. . Acids used for activation include inorganic acids such as sulfuric acid, hydrochloric acid, hydrobromic acid, and nitric acid, organic acids such as formic acid, acetic acid, propionic acid, paratoluenesulfonic acid,
and Lewis acids such as aluminum chloride and boron trifluoride. The amount of acid to be used is in the range of 0.01 to 10 mol, preferably 0.05 to 5 mol, per 1 mol of the carbonyl compound of formula (). In addition, tin compounds used in the present invention include metal tin, divalent tin compounds; for example, stannous chloride, stannous bromide, stannous acetate, stannous oxide, stannous sulfate, methoxy Stannous; Tetravalent tin compounds; examples include stannic chloride, stannic bromide, diallyltin dihalide, and the like. In addition, these tin compounds can be used alone or in combination, and the amount used is determined by the formula ()
The amount is less than the stoichiometric amount, that is, the amount equivalent to 0.001 to 0.5 mole, particularly preferably the amount equivalent to 0.05 to 0.1 mole, per mole of the carbonyl compound. Further, the metal aluminum used in the present invention is used in an amount equal to or more than 1 mole of the carbonyl compound of formula (). In addition, this reaction is carried out by a simple reaction procedure in which the carbonyl compound of the general formula (), the allyl halide of the general formula (), metal aluminum, and the tin compound are placed in the same reactor and mixed and stirred for several minutes or several hours. . The reaction temperature at that time is -50℃~200℃
The temperature is generally 0.degree. C., and preferably room temperature to 100.degree. In addition, in the reaction system in which this method is carried out, the high-valent tin compound produced when used in the allylation reaction is reduced with metal aluminum to regenerate the active low-valent tin compound, which is then further used. By using a circulation system of tin compounds, the desired allylation reaction can be carried out using less than the stoichiometric amount of metallic tin and/or divalent tin compounds and/or tetravalent tin compounds. Can be done again. Therefore, in the second invention, in an organic solvent containing a proton donor, the general formula () [In the formula, R ₁ and R ₂ each represent a hydrogen atom, an alkyl group, a cycloalkyl group, an aralkyl group, an aryl group, an alkynyl group, or an alkenyl group,
or R ₁ and R ₂ jointly represent one cycloalkyl group] and a carbonyl compound represented by the general formula () [In the formula, R ₂ , R ₄ , R ₅ , R ₆ and R ₇ each represent a hydrogen atom, an alkyl group, a cycloalkyl group, an aralkyl group, an aryl group, an alkynyl group, or an alkenyl group, or R ₃ and R ₅ , R ₃ and R ₆ , R ₅ and R ₆ , and R ₆ and R ₇ jointly represent one cycloalkyl group, and X represents a halogen atom]
General formula (a) and /or (b) [In the formula, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ and R ₇ each have the above-mentioned meanings] is produced, and further the reaction product is produced from the reaction system. Homoallylic alcohol derivatives of formula (a) and/or (b) of the compound were recovered, and the metal tin and/or the divalent tin compound and/or the tetravalent tin compound were used in the allylation reaction. The high-valent tin compounds generated during the process are treated with a reducing agent that converts them into active low-valent tin compounds to regenerate the active low-valent tin compounds, and the recycled low-valent tin compounds are reused. The carbonyl compound of formula (), the allyl halide compound of formula (), and metal aluminum are reacted again in the presence of a stoichiometric amount or less of this low-valent tin compound. ) and/or (b). In this second method of the invention, the reducing agent is preferably metallic aluminum, although other reducing metals can also be used. In addition, the regeneration and reuse of low-valent tin compounds can be repeated over multiple stages, making it possible to recycle tin compounds.
Good economy. The regeneration reaction of the low-valent tin compound can be carried out while the carbonyl compound of the formula () used in the next reaction step is made to coexist with the allyl halide compound of the formula () and metal aluminum; in this case, the latter of metallic aluminum can act as a reducing agent for the regeneration reaction (Example 28).
reference). Next, the present invention will be specifically explained with reference to examples. The first invention is based on Examples 1 to 27, and the second invention is
The present invention is illustrated by Examples 28-29, but is not limited to these Examples. Example 1 0.212 g of benzaldehyde (2
mmol), stannous chloride 0.076g (0.2 mmol), metallic aluminum 0.054g (2 mmol),
Weigh out 0.32 g (4 mmol) of allyl chloride. In it, 1.8ml of methyl cellosolve, 0.2ml of glacial acetic acid and water.
Add 1.0 ml and heat and stir at 40-50°C for 6 hours.
After the reaction, a saturated aqueous sodium bicarbonate solution is added to neutralize, and the precipitate is removed by suction. The liquid is n-hexane/ethyl acetate (2:1)
After extracting three times with a mixed solvent and washing twice with saturated brine, drying over anhydrous sodium sulfate, the n-
Hexane and ethyl acetate are distilled off under reduced pressure.
The resulting residue was applied to column chromatography using a silica gel fixed bed to separate 269.7 mg of allyl phenyl carbinol (yield 91%). It was confirmed that it was allyl phenyl carbinol by nuclear magnetic resonance absorption spectrum and infrared absorption spectrum. Spectral data are shown in Table 2. Examples 2-8 The method of Example 1 was repeated using the carbonyl compounds listed in Table 1 instead of benzaldehyde and using the reaction temperatures and times listed in Table 1. The results are shown in Table 1. Nuclear magnetic resonance absorption spectrum and infrared absorption spectrum data are shown in Table 2.

[Table] However, the yields in Table 1 are based on carbonyl compounds.

【table】

[Table] Example 9 106 g of benzaldehyde (0.1
mol), stannous chloride 0.9g (0.005 mol), metallic aluminum 4g (0.15 mol), allyl chloride 15.3g
(0.2 mol). Add 30 ml of methyl cellosolve, 3 ml of glacial acetic acid, and 15 ml of water to the mixture, and heat and stir at 40 to 50°C for 6 hours. After the reaction, the precipitate was filtered off, diluted sulfuric acid was added to the solution, extracted with n-hexane/ethyl acetate (2:1), washed twice with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed. Distill under reduced pressure. The resulting residue is analyzed using gas chromatography to obtain allyl phenyl carbinol in a yield of 88% (based on benzaldehyde). Examples 10 to 14 The method of Example 9 was repeated by using 0.01 mol of the tin compound listed in Table 3 instead of 0.9 g (0.005 mol) of stannous chloride in Example 9, and adding the additives listed in Table 3. repeated. The results are shown in Table 3.

[Table] However, the yield is based on benzaldehyde.
Examples 15-24 In Example 9, 30 ml of the solvent listed in Table 4 was used instead of 30 ml of methyl cellosolve, and 0.9 g (0.005 mol) of stannous chloride was replaced with stannous chloride.
The method of Example 9 was repeated using 1.9 g (0.01 mole). The results are shown in Table 4.

[Table] Example 25 Using 9.8 g (0.1 mol) of cyclohexanone instead of 10.6 g of benzaldehyde in Example 9,
In addition, 24.1g of allyl bromide instead of allyl chloride
The reaction and post-treatment were carried out in the same manner as in Example 9 except that (0.2 mol) was used. As a result, 1-allylcyclohexanol was obtained with a yield of 87% (based on cyclohexanone). Examples 26 to 27 Reactions and post-treatments were carried out in the same manner as in Example 9, except that allyl halide compounds listed in Table 5 were used in place of allyl chloride. The results are shown in Table 5. Also, the product 1-phenyl-2-methyl-3-buten-1-ol
H'-NMR spectrum and IR spectrum data are shown in Table 6.

【table】

[Table] Example 28 In Example 9, 10.6 g of benzaldehyde
(0.1 mol) using 1.9 g (0.01 mol) of stannous chloride instead of using 0.9 g of stannous chloride,
The reaction was carried out in the same manner as in Example 9. After the reaction, add 100ml of benzene to extract the product. This extraction was repeated a total of three times. The benzene layer is washed with saturated brine, and the solvent is distilled off. The obtained residue was analyzed by gas chromatography, and allyl phenyl carbinol was obtained in a yield of 90% (based on benzaldehyde) [first stage reaction]. Next, benzaldehyde is added to the water layer remaining in the reactor.
10.6g (0.1mol), allyl chloride 15.3g (0.2mol),
Adding 4 g (0.15 mol) of metallic aluminum, 10 ml of methyl cellosolve, and 3 ml of acetic acid, and performing the same reaction conditions and post-treatment as in the first stage reaction above, the yield was 87%.
Allyl phenyl carbinol was obtained (value based on benzaldehyde standards) [second stage reaction]. Furthermore, when the water layer remaining in the reactor is subjected to the same reaction and post-treatment as in the second stage reaction, the yield is 89%.
Allyl phenyl carbinol was obtained (value based on benzaldehyde standards) [third stage reaction]. Example 29 In Example 28, 10.6 g of benzaldehyde
(0.1 mol) instead of 9.8 g (0.1 mol) of cyclohexanone
15.3 g (0.2 mol) of allyl chloride
The same reaction and post-treatment as in Example 28 were carried out in three steps, except that 24.1 g (0.2 mol) of allyl bromide was used instead of 1-allylcyclohexanol, and the desired 1-allylcyclohexanol was obtained in the following yield ( cyclohexanone standard value). 1st stage reaction 2nd stage reaction 3rd stage reaction 85% 82% 87%

Claims (1)

[Claims] 1. General formula () in an organic solvent containing a proton donor [In the formula, R ₁ and R ₂ each represent a hydrogen atom, an alkyl group, a cycloalkyl group, an aralkyl group, an aryl group, an alkynyl group, or an alkenyl group,
or R ₁ and R ₂ jointly represent one cycloalkyl group] and a carbonyl compound represented by the general formula () [In the formula, R ₃ , R ₄ , R ₅ , R ₆ and R ₇ each represent a hydrogen atom, an alkyl group, a cycloalkyl group, an aralkyl group, an aryl group, an alkynyl group, or an alkenyl group, or R ₃ and R ₅ , R ₃ and R ₆ , R ₅ and
R ₆ , R ₆ and R ₇ jointly represent one cycloalkyl group, and X represents a halogen atom] and metal aluminum are combined into metal tin and/or divalent tin compounds. and/or the general formula (
a) and/or (b) A method for producing a homoallyl alcohol derivative represented by the formula [wherein R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , and R ₇ each have the above-mentioned meanings]. 2 General formula () in an organic solvent containing a proton donor [In the formula, R ₁ and R ₂ each represent a hydrogen atom, an alkyl group, a cycloalkyl group, an aralkyl group, an aryl group, an alkynyl group, or an alkenyl group,
or R ₁ and R ₂ jointly represent one cycloalkyl group] and a carbonyl compound represented by the general formula () [In the formula, R ₃ , R ₄ , R ₅ , R ₆ and R ₇ each represent a hydrogen atom, an alkyl group, a cycloalkyl group, an aralkyl group, an aryl group, an alkynyl group, or an alkenyl group, or R ₃ and R ₅ , R ₃ and R ₆ , R ₅ and R ₆ , and R ₆ and R ₇ jointly represent one cycloalkyl group, and X represents a halogen atom]
By reacting an allyl halide compound represented by the formula with metal aluminum in the presence of a stoichiometric amount or less of metal tin and/or a divalent tin compound and/or a tetravalent tin compound, the general formula (
a) and/or (b) [In the formula, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , and R ₇ each have the above-mentioned meaning] is produced, and further the reaction is carried out from the reaction system. The product homoallyl alcohol derivatives of formulas (a) and/or (b) are recovered and the metal tin and/or the divalent tin compound and/or the tetravalent tin compound are used in the allylation reaction. The high-valent tin compounds produced during this process are treated with a reducing agent that converts them into active low-valent tin compounds to regenerate the active low-valent tin compounds. The carbonyl compound of the formula (), the allyl halide compound of the formula (), and the metal aluminum are reacted again in the presence of a stoichiometric amount or less of this low-valent tin compound using the formula ( A method for producing the homoallyl alcohol derivative of a) and/or (b).