JPS6126532B2 - - Google Patents

Description

Detailed Description of the Invention The present invention provides acetone dialkyl acetal (herein, alkyl refers to an alkyl group having 3 to 4 carbon atoms) and 3-methyl-2-buten-1-ol (hereinafter referred to as prenol). ) in a solvent and the resulting alcohol is removed by azeotropy with the solvent to advance the reaction to produce 3,3-dimethyl-1-hexen-5-one.

This compound is an important compound as an intermediate in the production of synthetic pyrethroid insecticides.

Since it was reported that 2,2-dimethyl-3-(2,2-dihalobinyl)-cyclopropanecarboxylic acid derivatives are useful as insecticides (M.Elliott
et al.: Nature, 244 , 456 (1973)), research has begun on the production method of 2,2-dimethyl-3-(2,2-dihalobinyl)-cyclopropanecarboxylic acid, which is its constituent component, and many reports have already been published. being done. Among these carboxylic acids, 2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropanecarboxylic acid is considered to be the most useful.
Conventionally, 1,1-dichloro-4-methyl-1,3-
It was synthesized by an addition reaction between pentadiene and diazoacetic acid ethyl ester (J. Farka et al.
Coll.Czech.Chem.Commun. 24 , 2230 (1959)),
Due to the large number of steps involved and the use of difficult reactions, it has been desired to establish a more excellent practical manufacturing method. The inventors of the present invention have also conducted intensive studies based on this request, and have already
According to publications 95010, 95043, 95044, and 95045,
A highly advantageous manufacturing method is reported. The method proposed by the present inventors does not require expensive reagents such as sodium alkoxide to form a cyclopropane ring, and furthermore, the cis-form or trans-form can be produced at will, which is considered to be of revolutionary significance. It is something. 3,3-dimethyl-1-hexen-5-one, which is the object of the present invention, is a raw material compound in the above production method, and the present invention provides an economically advantageous production method thereof.

3,3-dimethyl-1- which is the object of the present invention
Hexen-5-one is a compound known in the literature,
The following synthesis method is known.

(1) K. Brack et al., Helv.Chim.Acta 34 , 2005
(1951) (2) Recherches 1960, 10 , 18-29 (3) NVKuznetsv et al., Ukr.Khim.Zh 32 (7), 725
~727 (1966) (4) Ger. Offen 2432232 (Cl. CO7C), 29
Jan.1976 Among these methods, method (1) allows the reaction to proceed reliably, but requires relatively expensive reagents such as ethyl orthoformate to obtain the raw material acetoacetate ethyl ethyl enol ether, and requires two steps. The problem is that it requires Method (2) produces an overwhelmingly large amount of by-products, and method (3) has an extremely low yield and must be carried out in a sealed tube.
Both are considered to have low practicality. Also, (4)
This method is considered unsuitable for mass production because it uses a Grignard reaction that is difficult to operate.

Therefore, the present inventors conducted additional trials on these synthetic methods and conducted intensive studies to industrially advantageously obtain the desired product. As a result, the present inventors found that it can be easily obtained using acetone dialkyl acetal and prenol as starting materials. They found a method and completed the present invention.

The method of the present invention can be said to have been established by developing it based on the method (3) above. That is, according to the document (3), the yield is 20% in a similar example, but there is no description of the yield for the target product, and furthermore, in the inventors' follow-up experiments, the similar product is shown in the reference example below. Therefore, it was considered that it was extremely difficult to effectively obtain the target object using this method. Furthermore, when paratoluenesulfonic acid or sulfuric acid, which are commonly used catalysts for acetal exchange, are added as a catalyst, the raw material prenol decomposes into isoprene and water as shown in the reference example below, making this production method difficult. has increased even more. In addition, if this reaction can only be carried out in a sealed tube as in the literature, large-scale industrial production using this reaction becomes increasingly unlikely.

However, as a result of strictly observing this reaction and continuing thorough studies to improve it, the present inventors found that when using the specific catalyst described below, or when using a weak base, which is normally considered to be a negative catalyst, They discovered the surprising and unexpected fact that acetal exchange proceeds even when the compound is added, and at the same time, they also discovered that by adding it, it is possible to prevent the decomposition of the raw materials and intermediates.

Furthermore, by carrying out this reaction in a suitable solvent and forcibly removing the generated alcohol from the system by azeotroping with the solvent, the desired Claisen rearrangement can be simultaneously achieved and completed. became possible.

Therefore, the present inventors were able to make a conventionally extremely difficult method into a practical method by selecting a catalyst and discovering an azeotropic solvent.

The reaction route of the present invention is believed to be as follows.

In the method of the present invention, the presence of strong acids is absolutely unacceptable, but those that should be present as catalysts or stabilizers include carboxylic acids such as succinic acid and phenylacetic acid, various phenols, quinoline, Examples include amines such as aniline, inorganic salts such as ammonium chloride, and organic salts such as quinoline hydrochloride and ammonium acetate.

Acetone dialkyl acetals that can be used in this reaction include acetone dimeropyl acetal and acetone dibutyl acetal.

As the solvent that can be used in this reaction, it is preferable to use a solvent that does not azeotrope with prenol, the acetone dialkyl acetal, or the target product, but only with the alcohol that is produced. Even if it boils, there is no problem in actually using it as long as the content is extremely small compared to the content of the alcohol produced. Solvents that can be used in this sense include aromatic hydrocarbons such as toluene, chlorobenzene, xylene, n-
Examples include aliphatic hydrocarbons such as octane and n-nonane, and ethers such as dibutyl ether.

It is also possible to use the acetone dialkyl acetal in excess of prenol as a solvent without using any particular solvent, in which case one of the above-mentioned solvents or higher It is also possible to coexist a solvent such as metaphenoxytoluene having a boiling point.

Since the present invention is a reaction carried out under refluxing of a solvent, it is natural that the reaction is carried out near the boiling point of the solvent, but a temperature of usually 100°C to 200°C or less is desirable.

In order to carry out the reaction of the present invention, it is sufficient to use a reaction apparatus equipped with a rectification column and distill off the fraction at the azeotropic temperature of the solvent used and the alcohol produced from the top of the column, which usually takes about 8 to 40 hours. It takes.

Acetone dipropyl acetal or acetone dibutyl acetal used as a raw material in the present invention is prepared from industrially available acetone dimethyl acetal and propanol or butanol in the presence of a catalyst such as a weak acid or weak base or an inorganic or organic salt as exemplified above. Alternatively, it can be obtained by performing ether exchange in the absence of the compound and removing the generated methanol by azeotropy together with a suitable solvent. Usually, an acid is used as a catalyst in acetal exchange by such an ether exchange reaction (Org.Syn., Coll.Vol.V,
5) Surprisingly, the reaction is not inhibited by the presence of a weak base such as a tertiary amine, and the objective can be achieved.

Solvents that can be used in this acetal exchange reaction include hydrocarbon solvents such as benzene, n-hexane, and n-heptane, chlorine-containing solvents such as chloroform, carbon tetrachloride, 1,1,2-trichloroethylene, and acetonitrile. Nitrogen-containing solvents such as , and oxygen-containing solvents such as methyl butyl ether can be mentioned. Similar to the reaction in the present invention described above, this acetal exchange reaction can also be achieved by using a rectification column and distilling off the fraction at the azeotropic temperature of the solvent used and methanol from the top of the column.

If the reaction of the present invention described above is used, the desired 3,3-dimethyl-1-hexen-5-one can be obtained in high yield from easily available acetone dialkyl acetal and prenol in an extremely simple manner. It became possible to synthesize 2,2-dimethyl-3-(2,2-
This makes it possible to synthesize large-scale synthesis of (dichlorovinyl)-cyclopropanecarboxylic acid.

The present invention will be described in more detail with reference to Reference Examples and Examples below, but it goes without saying that the present invention is not limited thereto.

Reference Example 1 10g of prenol is dissolved in 100ml of toluene, 0.3g of para-toluenesulfonic acid is added to this, heated, and the mixture is distilled from the top of the helivac rectification column to a boiling point of 34~
When the composition of the fraction at 36°C was investigated by gas chromatography, the main component was isoprene (column used: Porapak Q, 80-100 mesh, 2 m,
Column temperature 160℃, _N2 pressure 1Kg/ ^cm2 , detector FID).
When heating was continued further, separation of water was observed.

Reference Example 2 8.6 g (0.1 mol) of prenol, 12.5 g (0.12 mol) of acetone dimethyl acetal, and 0.1 g of ammonium chloride are dissolved in 100 ml of chloroform, heated to reflux, and heated to a boiling point of 53 to 55°C from the top of the helipad rectification column.
38.6 g of the fraction was distilled off in 16 hours. After cooling, add 2 g of potassium carbonate (anhydrous) to the reaction solution and stir.
After filtration, this is distilled under reduced pressure, and the boiling point is
6.0 g of a fraction with a boiling point of 67-85°C/53 mmHg was obtained, and 4.2 g of a fraction with a boiling point of 90-110°C/18 mmHg was obtained as a back distillate.
From the NMR spectrum data, the front distillate was acetone methyl prenylacetal and the rear distillate was acetone dibrenyl acetal.

NMR δ ^CDCl3 _TMS ; Front distillate 1.38 (6H, S), 1.6
7
(3H, broad S), 1.73 (3H, broad S), 3.20
(3H, S), 3.95 (2H, d, J=7Hz), 5.33
(1H, m) Rear 1.38 (6H, S), 1.67 (6H, broad
S), 1.73 (6H, broad S), 3.93 (4H, d,
J = 7Hz), 5.33 (1H, m) Reference Example 3 0.1g of succinic acid was added to 5g of acetone methylprenyl acetal obtained in Reference Example 2 above, and after heating under reflux for 4 hours, the composition of the reaction solution was examined using NMR. As a result, acetone dimethyl acetal, acetone methyl prenylacetal, and acetone diprenyl acetal were present in a ratio of approximately 1:2:1, respectively, and the target product, 3,3-dimethyl-
1-hexen-5-one was not present. The component abundance ratio was calculated based on the fact that the δ value of the methyl group in Reference Example 2 and the δ value of the methyl group in acetone dimethyl acetal (δ ^CDCl3 _TMS =1.32) were different.

Example 1 187.2 g (1.8 mol) of acetone dimethyl acetal, 216 g (3.6 mol) of propanol, and 0.1 g of ammonium chloride were added to 1 mol of chloroform and heated to reflux.
A 900 ml fraction of ~56°C was distilled off in 30 hours. After cooling, 255 g of acetone dipropyl acetal having a boiling point of 61-76°C/54 mmHg was obtained by distillation under reduced pressure. Yield 88.5% ⁿ²⁰ . ⁵ _D ; 1.4030 IR υ ^nax cm ^-1 ; 1380, 1215, ₁₁₆₃ , 1065,
1000, 870 NMR δ ^CDCl3 _TMS ; 0.92 (6H, t, J=6Hz)
, 1.35
(6H, S), 1.48 (4H, m), 3.35 (4H, t, J
= 6 Hz) Acetone dipropyl acetal obtained here 19.2
g (0.12 mol), 8.6 g (0.1 mol) of prenol, and 0.1 g of succinic acid were added to 10 g of monochlorobenzene, heated to reflux, and 18.4 g of a fraction with a boiling point of 65 to 95°C was collected from the top of the Vigrieu column rectification column for 30 hours. In short, he left. Distill the reaction solution as it is under normal pressure to determine the boiling point.
15.9 g of a fraction having a temperature of 114 to 140°C was obtained.

As a result of gas chromatography analysis, the composition of this substance was 42.9% monochlorobenzene, 3,3-dimethyl-1
-hexen-5-one 55.4%, yield 70%
It was hot. The NMR of the target product obtained here is a separately synthesized product (by method (1) in the detailed description of the invention)
completely matched that of

Example 2 16 g (0.1 mol) of acetone dipropyl acetal, 4.3 g (0.05 mol) of prenol, and 0.1 g of succinic acid were added to 10 g of metaphenoxytoluene, heated to reflux, and passed from the top of the Vigriu column rectification tower to a boiling point of 70 to 90. 7.9 g of the fraction at °C was distilled off over 30 hours. .
Distill the reaction solution under reduced pressure to obtain a boiling point of 46℃/67mmHg~85
7.0 g of a fraction with a temperature of 77 mmHg was obtained, and metaphenoxytoluene was recovered. The composition of the product thus obtained was 70.8% of the target substance and 21.6% of propanol, and the yield was 78.7%.

Example 3 Acetone dipropyl acetal 19.2 g (0.12 mol), prenol 8.6 (0.1 mol) and succinic acid
0.1 g was added to 10 g of meta-xylene, the reaction was carried out in the same manner as in Example 1, and 15 g of a fraction with a boiling point of 65 to 85°C was distilled off to obtain 15.7 g of a fraction with a boiling point of 115 to 140°C. The composition of this product was 50.7% metaxylene, 48.9% the target product, and the yield was 60.9%.

Example 4 Quinoline instead of succinic acid in Example 1
Using 0.1g, using a Helipack rectification tower instead of the Vigriu rectification tower, and 30g of chlorobenzene,
The others were reacted in the same way using the same amount and had a boiling point of 80 to 122℃.
17.2g of fraction was distilled off in 40 hours, boiling point 67-80/89
28.6 g of a fraction of °C/mmHg was obtained. The composition of this product was 64.8% chlorobenzene and 33.6% of the target product, and the yield was 76.3%.

Example 5 The same amount of meta-xylene was used in place of chlorobenzene in Example 4, and the reaction was carried out in the same manner to achieve a boiling point of 69°C/
36.3 g of a fraction of 83 mmHg to 72°C/80 mmHg was obtained. The composition of this product is 72.2% meta-xylene and 25.5% target substance.
%, and the yield was 73.5%.

Example 6 Acetone dimethyl acetal 104g (1 mol),
Butanol 163g (2.2mol) and succinic acid 0.2
Add 1 g of chloroform to 1 ml of chloroform, heat to reflux, and collect 900 ml of a fraction with a boiling point of 53 to 56°C from the top of the Helipak rectification column.
was distilled off in 30 hours. After cooling, reduce the temperature to 90% by vacuum distillation.
169 g of acetone dibutyl acetal having a temperature of 114°C/50mmHg was obtained. Yield 89.8% Acetone dibutyl acetal obtained here 45.2g
(0.24 mol), 17.2 g (0.2 mol) of prenol, and 0.1 g of succinic acid were added to 60 g of chlorobenzene and heated to reflux.
56.3 g of a fraction at 114°C was distilled off over 24 hours, and 53.2 g of a fraction with a boiling point of 70-90°C/110 mmHg was obtained by subsequent distillation under reduced pressure.

The composition of this product is 54.2% chlorobenzene and 33.6% of the target product, giving a yield of 70.9%.

Claims (1)

[Claims] 1. Acetone dialkyl acetal (here, alkyl refers to an alkyl group having 3 to 4 carbon atoms) and 3-methyl-2-buten-1-ol are added to toluene and chlorobenzene in the presence of succinic acid or quinoline. , xylene, n-octane,
The reaction is carried out in an organic solvent selected from n-nonane and dibutyl ether or in an excess amount of acetone dialkyl acetal, and the resulting alcohol is removed by azeotropy with the organic solvent or acetone dialkyl acetal. Characteristics of 3,3-dimethyl-1-hexene-5
-Production method of on.