JPS61233647A - Production of 2,2,3,3,-tetramethylcyclopropane-1-carboxylic acid - Google Patents

Abstract

PURPOSE:To obtain the titled substance which is a synthetic intermediate for pyrethroid based insecticides and acaricides, e.g. fenpropathrin, safely and advantageously using raw materials available at a low cost, by reacting a novel halogenoketone compound as a starting material with an alkali hydroxide. CONSTITUTION:A novel halogenoketone compound expressed by formula I (X is C1 or Br) is reacted with an alkali hydroxide, preferably in an amount within 2-15 mol range based on one mol compound expressed by formula I in a solvent, e.g. methanol or water, at 20-100 deg.C to give the aimed compound. The compound expressed by formula I is synthesized by reacting 2,3-dimethyl-2- butene expressed by formula II with acetyl chloride in the presence of a Lewis acid, and halogenating the resultant compound expressed by formula III.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing 2.2.8.8-tetramethylcyclopropane-1-carboxylic acid (hereinafter referred to as tetramethyl acid).

Tetramethyl acid is a compound represented by the formula (I), which is an acid component of pyrethroid insecticidal and acaricidal compounds such as fenpropathrin, and is an extremely useful synthetic intermediate. .

Until now, a typical method for synthesizing tetramethyl acid is to react 2,8-dimethyl-2-butene with ethyl diazoacetate to produce ethyl 2.2°8.8-tetramethylcyclopropanecarboxylate. A method of synthesis and subsequent hydrolysis is known (Matsui et al., Agr. B.
iol, Ohem,.

81.1148 (1967)). Although kinetics has the advantage that the desired product can be obtained in a short process, it requires the use of ethyl diazoacetate, which has the potential for explosion, so it is not suitable for large-scale synthesis on an industrial scale. This has the disadvantage of requiring special precautions in terms of safety.

002C2tf5 Under these circumstances, the present inventors conducted extensive studies on the method for producing tetramethyl acid represented by the above formula (1), and found that a novel general formula (n) [wherein X is a chlorine atom] Or represents a bromine atom. ] It was discovered that tetramethyl acid can be produced very advantageously by using the halogenoketone compound shown as an intermediate raw material and reacting it with an alkali hydroxide, leading to the present invention.

According to the method of the present invention, compared to the conventional method described above, cheaper reagents can be used as raw materials for synthesis, and the reaction can be carried out more safely. This is extremely advantageous as a law.

The method of the present invention will be explained below.

The most common alkali hydroxide used in the present invention is sodium hydroxide, potassium hydroxide, etc., and the amount thereof is 2 to 15 mol per mol of the halogenoketone compound represented by the general formula (■). range.

The reaction solvent is usually water, methanol, ethanol,
A single or mixed polar solvent such as tetrahydrofuran or dioxane is used, but it is also possible to carry out the reaction in a two-phase system such as toluene-water in the presence of a phase transfer catalyst such as quaternary ammonium.

The reaction temperature is usually 20°C to 100°C.

In addition, the general formula (II) which is the raw material compound of the above-mentioned method of the present invention
The halogenoketone compound represented by is 2゜8-dimethyl-
It can be efficiently obtained from 2-butene by the route shown below.

(Ill) That is, by reacting 2,8-dimethyl-2-butene with acetyl chloride in the presence of a Lewis acid, antitoxin 1→1 formula (m)
A halogenoketone represented by the general formula (II) can be obtained by introducing a ketone compound represented by formula (II) and then halogenating the nucleated product.

In the above synthetic route, metal chlorides such as ferric chloride, zinc chloride, aluminum chloride, stannic chloride, and antimony trichloride are listed as Lewis acids used in the step of obtaining the ketone compound represented by the formula Cm>. The amount used is 0.00 per mole of 2,8-dimethyl-2-butene.
It ranges from 1 mol to 1 mol. The reaction temperature may vary depending on the amount of Lewis acid used, but it is 50°C to 80°C, and the range of -20°C to 10°C is usually preferred from the viewpoint of yield.
The reaction time in this reaction may vary depending on the type and amount of Lewis acid used and the reaction temperature, but generally it is within 10 hours, more preferably within 2 hours, since the reaction proceeds very quickly.

Further, the amount of acetyl chloride used is usually in the range of 1.0 to 1.5 mol per 1 mol of 2,8-dimethyl-2-butene.

Furthermore, in order to carry out the reaction more smoothly, an inert solvent such as dichloromethane or dichloroethane may be used as the reaction solvent.

In addition, as the chlorinating agent or brominating agent used in the step of obtaining the halide ketone represented by the general formula (II) from the ketone compound represented by the formula (m) thus obtained, chlorine 1. Examples include bromine, sulfuryl chloride, phosphorus pentabromide, and N-promsuccinimide, and the amount used is usually 0.7 to 1 mole of 8.8.4-trimethyl-4-chloro-2-pentanone ~1.5 times the mole.

Examples of solvents that can be used in this reaction include water, methanol, acetic acid, dichloromethane, and chloroform.

The reaction temperature is usually 0°C to 60°C, and the reaction time is usually 1 to 24 hours, although it may vary depending on the solvent used, the type of chlorinating agent or brominating agent, and the reaction temperature. In addition, in order to carry out the reaction more smoothly, it is possible to add a -soot amount of hydrogen chloride or hydrogen bromide to the reaction system, or to add a dehydrohalogenating agent such as amines, lime carbonate, or potassium chloride. You can also do it.

Next, the present invention will be explained in more detail with reference to Examples.

Example 1 2,3-dimethyl-2-butene 20.0f (0,288
mol) in 50 mj of dichloroethane, 20.5 f (0,261 mol) of acetyl chloride was added thereto, and 8.2 IC0 of zinc chloride was added at 0°C while stirring under water cooling.
, 0285 mol) was added to each raw feces. At this time, an increase in internal temperature was observed, but the temperature of the reaction solution was kept below 5°C.

After stirring for an additional 80 minutes at 0 to 5°C, the reaction solution was poured into ice water and separated. The dichloroethane layer was washed with water, dried over magnesium sulfate, and then concentrated (~80°C/70 days) to obtain a pale yellow oil as a residue (yield 7).
5%).

This thing is the target from its NMIL spectrum! 3
, 8.4-trimethyl-4-chloro-(10') Confirmed to be 2-pentanone, it tends to cause a hydrogen reaction and reduce the yield, so only remove the low boiling point during distillation. It is preferable to keep it at .

NMR data (δ value, cpcza) 1.30 (9,6E[), 1.60 (51,6I(
).

2.28 (S, 3H) Example 2 3. Dissolve 8.0 g of 4-trimethyl-4-chloro-2-bentanone in 80 d of dichloromethane, add 2 drops of dicyclohexylamine, and then Sulfuryl chloride 10, Of was added dropwise at 0°C. After dripping, 20
After stirring at °C for 24 hours, the reaction solution was poured into ice water and extracted with dichloromethane. The dichloromethane layer was washed with water, dried over magnesium sulfate, and concentrated. The concentrated sample was subjected to silica gel column chromatography, and 6.1 g of 1
．． 4-Dichloro-8,8,4-trimethyl-2-pentanone (a compound in which the substituent X is a chlorine atom in the above formula (■)) was obtained as a pale yellow oil.

Refractive index 1.4778 (25.5°C) NMR data (δ value, 0DO1a) 1.87 (8,611), 1.62 (1,6H), 4
．． 65 (3,214') Example 3 8.8. Dissolve 2.2 f of 4-1-riftyl-4-chloro-2-pentanone in 15-methanol and dissolve 2.50 g of bromine (1,2 2 times the mole) was added dropwise and stirred for 1 hour. The reaction solution was poured into ice water and extracted twice with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated to obtain the desired 1-pro7-4-chloro 8.8.
4--TrimethyJ-2-beniftanone (the general formula (
Halogenoketone compound 11 in which substituent X is a bromine atom in I[)! ! J) 8.1N was obtained (yield 96%).

Refractive index 1.5000 (21.5°C) NMR (δ value, 0DOta) 1.87 (8,6H), 1.59 (tei, 6H) 4.80
(1,2H) Example 4 A solution of 2.7 g of 1,4-dichloro-8,8,4-)rifthyl-2-pentanone in tetrahydrofuran 10-
It was added dropwise at 40°C to a solution consisting of 6.01 parts of sodium hydroxide, 50 parts of water, and 85 parts of tetrahydrofuran. After the addition, the mixture was further stirred at 25° C. for 12 hours, and the reaction solution was poured into ice water and extracted with ether to remove the neutral portion. The aqueous solution was acidified with hydrochloric acid and extracted twice with ether. The ether layer was washed with brine, dried over magnesium sulfate, and the ether was distilled off to obtain white crystals 1.601 (yield: 82.2%).
).

This product had a melting point of 119.8°C and was synthesized from ethyl diazoacetate and 2,8-dimethyl-2-butene.
．． 8.8-Tetramethylcyclopropane-1-carboxylic acid (1B). (Matsui, Kitahara et al., Agr, Biol, Ohem,
, vol. 31, 114g (1967)).

Example 6 1-bromo-4-chloro-8,8,4-trimethyl-2
- A solution of 4.1f pentanone in dioxane 10- is mixed with 8.81° of potassium hydroxide, 80-80 of water and 20-
- into a solution consisting of 2.2.8.8-tetramethylcyclopropane-, and then stirred at 20°C for 15 hours. 1.8 g (yield 76%) of 1-carboxylic acid was obtained as white crystals.

(14 completed)

Claims (3)

[Claims] (1) General formula▲There are mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, X represents a chlorine atom or a bromine atom. ] A method for producing 2,2,3,3-tetramethylcyclopropane-1-carboxylic acid, which comprises reacting a halogenoketone compound represented by the following with an alkali hydroxide. (2) 3,3,4-trimethyl-4-chloro-2-pentanone is reacted with a chlorinating agent or a brominating agent to produce the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, X is chlorine] Represents an atom or a bromine atom. ] 2, characterized in that the compound is introduced into a halogenoketone compound represented by the formula, and then the compound is reacted with an alkali hydroxide.
, 2,3,3-tetramethylcyclopropane-1-carboxylic acid production method. (3) 2,3-dimethyl-2-butene is reacted with acetyl chloride in the presence of a Lewis acid to obtain 3,3,4-trimethyl-4-chloro-2-pentanone, which is then chlorinated with the pentanone. or a brominating agent, and the general formula ▲ has numerical formulas, chemical formulas, tables, etc. ▼ [In the formula, X represents a chlorine atom or a bromine atom. ] 2, characterized in that the compound is introduced into a halogenoketone compound represented by the formula, and then the compound is reacted with an alkali hydroxide.
, 2,3,3-tetramethylcyclopropane-1-carboxylic acid production method.