JP3805435B2 - Process for producing 6-methyl-3-hepten-2-one - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a process for producing 6-methyl-3-hepten-2-one by aldol condensation of isovaleral and acetone. 6-Methyl-3-hepten-2-one obtained by the present invention is useful as an intermediate for synthesis of various fine chemicals. For example, by hydrogenation, it can be used as a raw material for synthesis of isophytol [Journal of Organic Synthetic Chemical Society, Vol. 20, pp. 824-836 (1962)], or as a synthetic raw material for fragrances such as tetrahydrolinalol and dihydrogeraniol (see Bull. Soc. Chim. Fr., 1586 (1955) etc.) -Can be converted to methyl-2-heptanone.
[0002]
[Prior art]
It has long been known as an aldol reaction that a carbonyl compound such as an aldehyde or ketone is condensed in the presence of a basic catalyst to produce an aldol or ketol. For example, isovaleral and acetone are easily self-condensed in the presence of a basic catalyst to change to the corresponding aldol or ketol, and then dehydrated within the molecule to form an α, β-unsaturated carbonyl compound as an aldol condensation product. (See, for example, “Organic Reactions Vol. 16,” pages 88 and 112, JOHN WILEY & SONS, INC.). Such an α, β-unsaturated carbonyl compound is easily changed to a higher-order condensate by an aldol reaction.
[0003]
An aldol reaction between two different carbonyl compounds is known as a crossed aldol reaction. In the crossed aldol reaction, a wide variety of reaction products are often generated, and an aldol condensate obtained by condensing two kinds of carbonyl compounds in a one-to-one relationship (hereinafter, this may be referred to as a one-to-one condensate). It is generally difficult to obtain selectively. In the crossed aldol reaction, in order to increase the selectivity of the one-to-one condensate based on one of the two types of carbonyl compounds, an effort has been made to use the other carbonyl compound in excess.
[0004]
A method for producing 6-methyl-3-hepten-2-one by using an aqueous alkaline solution as a basic catalyst and subjecting isovaleral and acetone to aldol condensation is known. For example, the followings are known.
(1) A method in which an equimolar mixture of isovaleral and acetone is shaken at 20 to 25 ° C. in the presence of an aqueous sodium hydroxide solution (see Journal of Chemical Society of Japan, Vol. 59, p. 224 (1938)).
(2) A method in which isovaleral is added to a mixture of acetone, ether and an aqueous solution of sodium hydroxide 4 times mol with respect to isovaleral while maintaining the reaction temperature at 15 ° C. or lower [Bull. Soc. Chim. Fr., 112 (1957)].
[0005]
In addition to the above, the following (3) to (6) are known as methods for producing 6-methyl-3-hepten-2-one.
(3) A method of reacting isovaleral and acetone under pressure in the absence of a catalyst or heating in a pressure-resistant sealed container at high temperature (300 ° C.) and high pressure (270 kg / cm ² ) (see Japanese Examined Patent Publication No. 47-6281) ).
(4) A method of reacting isovaleral and acetone in the presence of zinc oxide at 180 ° C. and 35 atm (see US Pat. No. 4,005,147).
(5) A method in which isoamyl alcohol and acetone are condensed in the presence of aluminum isopropoxide (see The Chemical Society of Japan, Vol. 81, p. 675 (1960)).
(6) A method of reacting acetylacetylene and triisobutyl boron in the presence of oxygen (see J. Am. Chem. Soc., 92 , 3503 (1970)).
[0006]
[Problems to be solved by the invention]
However, since the methods described in (3) and (4) above require high temperature and high pressure conditions, special production facilities are required, and the conversion rate of isovaleral is 24% and 73%, respectively. It is low and not satisfactory. Further, the method described in (5) above requires the use of an equimolar amount of expensive aluminum isopropoxide with respect to isoamyl alcohol, and the method described in (6) above is very expensive acetyl. It is necessary to use acetylene and triisobutyl boron. As described above, the methods (3) to (6) are not industrially advantageous in terms of production facilities and raw material prices.
[0007]
On the other hand, the method of aldol condensation of isovaleral and acetone using an alkaline aqueous solution has an advantage that the reaction can be carried out under mild conditions using an inexpensive reagent. However, in the method (1), the yield of 6-methyl-3-hepten-2-one which is an aldol condensation product is only 35 to 40%. In the method (2), 6-methyl-4-hydroxyheptan-2-one is mainly obtained, and a dehydration reaction is required to obtain 6-methyl-3-hepten-2-one. Also, the yield of 6-methyl-3-hepten-2-one thus obtained is not satisfactory at 51%. Furthermore, the method (2) is not industrially advantageous in terms of recovery of acetone and volumetric efficiency of the reaction because an excessive amount of acetone is used.
[0008]
This invention is made | formed in view of this present condition, Comprising: It aims at providing the method which can manufacture 6-methyl-3-hepten-2-one industrially advantageously.
[0009]
[Means for Solving the Problems]
In order to solve the above-mentioned problems, the present inventors paid attention to the aldol condensation reaction of isovaleral and acetone using an aqueous alkaline solution, and as a result of repeated examination of the reaction conditions, the present invention was completed. That is, the present invention relates to ( 1) a method for producing 6-methyl-3-hepten-2-one by aldol condensation of isovaleral and acetone in the presence of an aqueous alkali solution, wherein the isovaleral and the aqueous alkali solution are each in acetone. (6) A process for producing 6-methyl-3-hepten-2-one characterized by reacting with continuous addition; (2) 6-methyl-3 by aldol condensation of isovaleral and acetone in the presence of an aqueous alkali solution; -A method for producing hepten-2-one, wherein a reaction is carried out while continuously adding isovaleral and an aqueous alkali solution to a mixed solution of acetone and 1/5 mol or less of isovaleral to acetone. Characteristic method for producing 6-methyl-3-hepten-2-one, (3) presence of alkaline aqueous solution A method for producing 6-methyl-3-hepten-2-one by aldol condensation of isovaleral and acetone below, wherein isovaleral is mixed in a mixed solution of acetone and an alkaline aqueous solution of 1 mol% or less with respect to the acetone. And 6-methyl-3-hepten-2-one .
[0010]
In the present invention, during most of the reaction, the ratio of acetone to isovaleral is controlled to be a large excess, so the selectivity of 6-methyl-3-hepten-2-one based on isovaleral is In addition, the amount of acetone used relative to isovaleral can be reduced. Further, in the present invention, since the alkali concentration at the initial stage of the reaction is controlled so as not to become so high, the selectivity to 6-methyl-3-hepten-2-one due to the runaway reaction is prevented. .
[0011]
DETAILED DESCRIPTION OF THE INVENTION
In the present invention, aldol condensation is carried out while continuously adding isovaleral and an aqueous alkali solution to acetone.
The ratio of acetone to isovaleral used in the reaction is not particularly limited, but in order to increase the selectivity of 6-methyl-3-hepten-2-one based on the more expensive isovaleral, acetone is used with respect to 1 mol of isovaleral. Is preferably in the range of 0.5 to 3 moles, and more preferably in the range of 0.8 to 2 moles of acetone with respect to 1 mole of isovaleral from the viewpoint of increasing the volumetric efficiency of the reaction. , Particularly preferably in the range of 0.9 to 1.2 mol.
[0012]
Examples of the alkali used in the present invention include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides such as barium hydroxide and calcium hydroxide; alkalis such as potassium carbonate. Metal carbonates; 1,5-diazabicyclo [5.4.0] undecene-5 (DBU), amine compounds such as piperidine, and the like. Among these, alkali metal hydroxides, alkaline earth metal Hydroxides are preferred.
In addition, one type of alkali may be used, or two or more types may be used in combination.
[0013]
The amount of alkali used is usually 0.001 to 0.2 mol with respect to 1 mol of isovaleral and 0.01 to 0.1 mol with respect to 1 mol of isovaleral from the viewpoint of reaction rate and production cost. Is preferred.
Moreover, the alkali concentration in the aqueous alkali solution is usually 0.5 to 30% by weight, preferably 1 to 10% by weight.
[0014]
The aldol condensation reaction according to the present invention is usually carried out in the absence of an organic solvent, but an organic solvent may be used as long as the reaction is not adversely affected. Usable organic solvents include, for example, aliphatic alcohol solvents such as methanol, ethanol, propanol, isopropanol, n-butanol, s-butanol, and t-butanol; tetrahydrofuran, 1,4-dioxane, diethyl ether, diisopropyl ether And ether solvents such as dibutyl ether; hydrocarbon solvents such as hexane, heptane, octane, benzene, toluene and xylene.
[0015]
Moreover, it is desirable to implement this invention in inert gas atmosphere, such as nitrogen and argon.
[0016]
The aldol condensation reaction according to the present invention is generally carried out by continuously adding isovaleral and an aqueous alkali solution to a reaction vessel equipped with acetone and equipped with a stirrer. “Continuous addition” as used in the present invention means feeding isovaleral and an aqueous alkali solution, but isovaleral and an aqueous alkali solution added in several portions as long as the gist of the invention is not impaired. The aspect of doing is included.
[0017]
The addition of Isobareraru and alkaline aqueous solution is normally started simultaneously, it is an amount of up to 1/5 moles with respect to acetone, it may be added prior to Isobareraru. On the other hand, when an excessive amount of the alkaline aqueous solution is added in advance, the amount of by-product due to self-aldol condensation of acetone or the like increases, and the selectivity to 6-methyl-3-hepten-2-one decreases. and will, but it is an amount up to about 1 mol% relative to acetone, it can be added in advance. Further, it is not preferable to mix isovaleral and an aqueous alkali solution and add it to acetone, since isovaleral itself undergoes self-aldol condensation and the selectivity to 6-methyl-3-hepten-2-one decreases.
[0018]
Addition of isovaleral and an aqueous alkali solution is usually adjusted so as to be completed at the same time, but either one of them may be terminated first unless it is extremely quick.
[0019]
The time required for adding isovaleral and an aqueous alkali solution varies depending on the type and concentration of the alkali used, but is usually 0.5 to 10 hours.
[0020]
The reaction temperature is usually in the range of −20 to 100 ° C., but in order to make the reaction rate practical and increase the selectivity to 6-methyl-3-hepten-2-one, It is preferably within the range of 80 ° C.
Further, the reaction may be carried out at normal pressure or under pressure.
[0021]
The aldol condensation reaction proceeds simultaneously with the start of the addition of isovaleral and the aqueous alkali solution, and is usually completed within 5 hours after the end of the addition.
In addition, it is desirable to sufficiently stir during the addition of isovaleral and an aqueous alkali solution and during the reaction.
[0022]
After completion of the reaction, the target product is obtained by, for example, distilling the reaction mixture after removing the aqueous layer, extracting from the reaction mixture with an organic solvent, and then distilling off the organic solvent under normal pressure or reduced pressure. It can be isolated by known methods.
Examples of the organic solvent include hydrocarbon solvents such as toluene, benzene, and cyclohexane; halogenated hydrocarbon solvents such as methylene chloride, chloroform, carbon tetrachloride, and dichloroethane.
[0023]
According to the present invention, 6-methyl-3-hepten-2-one, which is an aldol condensate of isovaleral and acetone, is produced in a high yield with a simple operation without requiring special production equipment, using an inexpensive raw material. can do. Further, according to the present invention, the amount of 6-methyl-4-hydroxyheptan-2-one, which is an aldol adduct of acetone and isovaleral, is usually 5 mol relative to 6-methyl-3-hepten-2-one. 6-methyl-3-hepten-2-one can be selectively obtained with a low content of about%.
[0024]
6-Methyl-3-hepten-2-one obtained by the present invention is described in, for example, the above-mentioned literature (see the Journal of Synthetic Organic Chemistry, Vol. 20, pp. 824-836 (1962)). In the following manner, isophytol, which is a synthetic intermediate of vitamin E, can be derived as follows. That is, 6-methyl-3-hepten-2-one is first converted to 6-methyl-2-heptanone by hydrogenation using palladium carbon as a catalyst. Next, after the obtained 6-methyl-2-heptanone was ethynylated with acetylene, a triple bond was selectively hydrogenated with a Lindlar catalyst to produce 3,7-dimethyl-1-octene-3- and all, then the hydroxy group is esterified with diketene, further subjected to Carroll rearrangement reaction, 6, to obtain a 10-dimethyl-5-ene-2-one. The thus obtained 6,10-dimethyl-5-undecene-2-one was subjected to ethynylation with acetylene, selective hydrogenation of triple bond using Lindlar catalyst, esterification of hydroxyl group with diketene, carol rearrangement reaction. depending on sequentially applying 6, 10,14- trimethyl-5,9 to obtain a penta octadecadienoic-2-one, followed by conversion by hydrogenation using a palladium carbon 6,10,14- trimethyl-2-pentadecanone To do. Then, isophytol can be obtained by subjecting 6,10,14-trimethyl-2-pentadecanone to ethynylation with acetylene and selective hydrogenation of triple bond using Lindlar catalyst.
[0025]
【Example】
EXAMPLES Hereinafter, although an Example demonstrates this invention concretely, this invention is not limited to this Example.
[0026]
Example 1
A stainless steel autoclave with an internal volume of 10 liters equipped with a stirrer was charged with 1403.1 g (24.2 mol) of acetone in a nitrogen atmosphere, the jacket temperature was set at 72 ° C., and the mixture was heated with stirring. When the temperature in the autoclave reached 68 ° C. and the pressure reached 1.9 kg / cm ² (gauge pressure), the 2% sodium hydroxide aqueous solution and isovaleral were fed at a rate of 774 g / hr for the former and 679 g / hr for the latter, respectively. Feeded continuously. The internal temperature gradually increased after the start of feeding. While maintaining the internal temperature at 70 to 72 ° C., the 2% aqueous sodium hydroxide solution and isovaleral were continuously fed for 175 minutes while stirring. The 2% sodium hydroxide aqueous solution fed during this period was 2253.7 g (1.12 mol as NaOH), and isovaleral was 1979.4 g (22.99 mol).
After the feeding of the 2% aqueous sodium hydroxide solution and isovaleral was completed, the temperature of the reaction mixture was kept in the above range, and stirring was continued for 1.5 hours to cool down to room temperature. The reaction mixture was taken out and allowed to stand to separate into two layers. The organic layer (upper layer) was separated and analyzed by gas chromatography. As a result, 1909.0 g (yield: 66%) of 6-methyl-3-hepten-2-one and 6-methyl- It was found that 107.3 g (yield: 3.3%) of 4-hydroxyheptan-2-one was contained. The conversion rate of isovaleral was 98.3%.
[0027]
2938.8 g of the organic layer obtained above was distilled under reduced pressure to obtain 1824.3 g (purity: 98%) of 6-methyl-3-hepten-2-one (bp: 113 to 115 ° C./100 mmHg). )Obtained.
[0028]
Example 2
A stainless steel autoclave with an internal volume of 10 liters equipped with a stirrer was charged with 1470 g (25.3 mol) of acetone and 217 g (2.52 mol) of isovaleral in a nitrogen atmosphere, and the jacket temperature was set to 60 ° C. The mixture was warmed with stirring. When the temperature in the autoclave reached 57.7 ° C. and the pressure reached 1.0 kg / cm ² (gauge pressure), 2% aqueous sodium hydroxide and isovaleral were added to the above mixture, the former was 774 g / hr, and the latter was Each was continuously fed at a rate of 605 g / hr. Heat generation started about 3 minutes after the start of feeding, and 5 minutes later, the maximum temperature reached 70.6 ° C. The maximum pressure reached 1.8 kg / cm ² after about 4 minutes from the start of heat generation.
Ten minutes after the start of feeding of the 2% aqueous sodium hydroxide solution and isovaleral, the temperature of the jacket was set at 70 to 72 ° C, and the reaction was continued while maintaining the internal temperature at 63.4 to 71.2 ° C. The feed of 2% aqueous sodium hydroxide and isovaleral was continued for 175 minutes, and 2256.2 g of a 2% aqueous sodium hydroxide solution (1.128 mol as NaOH) and 1764.1 g (20.51 mol) of isovaleral were added to acetone.
After the feeding of the 2% sodium hydroxide aqueous solution and isovaleral was completed, the reaction was continued for 1.5 hours at the same temperature, and the reaction was continued. The reaction mixture was taken out and allowed to stand to separate into two layers. When the organic layer (upper layer) was separated and analyzed by gas chromatography, 1926.1 g (yield: 66.5%) of 6-methyl-3-hepten-2-one and 6- It was found that 107.4 g (yield: 3.3%) of methyl-4-hydroxyheptan-2-one was contained. The conversion rate of isovaleral was 98.2%.
[0029]
Comparative Example A reactor having a capacity of 300 ml equipped with a stirrer was charged with 30.5 g (525 mmol) of acetone, 43.1 g (500 mmol) of isovaleral and 50 g of 2% aqueous sodium hydroxide solution (50 mmol of NaOH) in a nitrogen atmosphere. The resulting mixture was stirred at an internal temperature of 45 ° C. The internal temperature rose to 55 ° C. by reaction heat 5 minutes after the start of stirring. Thereafter, stirring was continued for 3 hours while maintaining the internal temperature at 55 to 65 ° C. After cooling to room temperature, the reaction mixture was taken out and allowed to stand to separate into two layers. The organic layer (upper layer) was separated and analyzed by gas chromatography. As a result, 65.7 g (yield: 56.6%) of 6-methyl-3-hepten-2-one and 6- It was found that 3.7 g (yield: 5.1%) of methyl-4-hydroxyheptan-2-one was contained. The conversion rate of isovaleral was 97.1%.
[0030]
Reference Example An organic layer 2823.3 [6-methyl- containing 6-methyl-3-hepten-2-one obtained in the same manner as in Example 1 in an autoclave having an internal volume of 5 liters equipped with a stirrer. 1-containing 3-hepten-2-one] and 1.93 g of 5% palladium carbon, and the inside of the autoclave was replaced with hydrogen gas, and the reaction system was charged with 9 kg of hydrogen gas. / Cm ² , and the internal temperature was raised to 120 ° C. The reaction was carried out in this state for 7 hours, and after cooling to room temperature, the catalyst was removed from the resulting reaction mixture by filtration.
When the obtained filtrate was analyzed by an internal standard method by gas chromatography [capillary column CBP-10 (manufactured by Shimadzu Corporation), 50 m, column temperature (70 → 170 ° C., heating rate 5 ° C./min)]. , 1890.4 g (14.4 mol, yield 100%) of 6-methyl-2-heptanone was found. Acetone was removed from the filtrate under normal pressure, and then low-boiling components (33 to 132 ° C.) were removed under a reduced pressure of 300 mmHg. The obtained residue was distilled under reduced pressure to obtain 1628.9 g (purity 99% or more) of 6-methyl-2-heptanone (boiling point: 103 ° C./100 mmHg).
[0031]
【The invention's effect】
According to the present invention, 6-methyl-3-hepten-2-one useful as a synthetic intermediate for various fine chemicals can be produced industrially advantageously.

Claims (4)

A method for producing 6-methyl-3-hepten-2-one by aldol condensation of isovaleral and acetone in the presence of an aqueous alkali solution, wherein the reaction is carried out while continuously adding isovaleral and an aqueous alkali solution to acetone. A process for producing 6-methyl-3-hepten-2-one. A method for producing 6-methyl-3-hepten-2-one by aldol condensation of isovaleral and acetone in the presence of an aqueous alkaline solution, comprising a mixture of acetone and 1/5 mol or less of isovaleral with respect to the acetone A process for producing 6-methyl-3-hepten-2-one, wherein the reaction is carried out while continuously adding isovaleral and an aqueous alkali solution. A method for producing 6-methyl-3-hepten-2-one by aldol condensation of isovaleral and acetone in the presence of an aqueous alkaline solution, comprising a mixed solution of acetone and an aqueous alkaline solution of 1 mol% or less based on the acetone A process for producing 6-methyl-3-hepten-2-one, wherein the reaction is carried out while continuously adding isovaleral and an aqueous alkali solution. The 6-methyl-3 according to claim 1, 2 or 3, wherein the alkali is at least one compound selected from the group consisting of hydroxides of alkali metals and hydroxides of alkaline earth metals. -Method for producing hepten-2-one.