JPS607616B2 - α,α-disubstituted acetate and its production method - Google Patents

Description

Detailed Description of the Invention The present invention is based on the general formula (where RI represents a saturated or unsaturated aliphatic hydrocarbon group having 1 to 20 carbon atoms, and R2 is substituted with a phenyl group, an alkyl group, or a halogen atom). The present invention relates to a novel Q.Q-disubstituted acetate represented by a phenyl group (n is an integer of 1 to 9) and a method for producing the same.

In general formula 1, RI is preferably methyl, ethyl,
Lower alkyl groups such as n-propyl, isopropyl, n-butyl, t-butyl; lower alkenyl groups such as allyl, prenyl, isoprobenyl; ** Terbene-based carbon hydrogen residues such as ethyl and isophytyl, particularly preferably lower alkyl groups or geranyl groups.

The aryl group as R2 is phenyl, tolyl, xylyl, naphthyl, etc., and these may be nuclear-substituted with one or more halogen atoms. The Q/Q-di-layer acetate represented by the general formula 1 can be led to a compound represented by the following general formula (i or (il)) by desulfonation by a method known per se. These substances themselves or as intermediates are extremely valuable substances in the fields of medicine, agricultural chemicals, fragrances, etc.

In particular, Q-falnesyl-Q-arylsulfonylacetic acid ester with n=3 can be desulfonated by simple reduction (e.g. using a lithium/ethylamine system) to produce farnesyl, which is useful as an anti-clumping agent or an intermediate thereof. It is extremely important because it can be used as acetate ester (see Japanese Patent Publication No. 39-561).

According to the present invention, the Q.Q-didirect acetate represented by the general formula 1 is represented by the following general formula (wherein X represents a halogen atom and n represents an integer from 1 to 9). It can be easily produced by reacting a compound represented by the formula R2S02CH2COORim with an arylsulfonylacetate represented by the general formula R2S02CH2COORim (wherein RI and R2 have the same meanings as those in the general formula 1) in the presence of a base.

Conventionally, methods for producing falnesyl acetic acid ester using falnesyl halide as a raw material include a method in which falnesyl halide is condensed with malonic acid ester, the product is hydrolyzed to form a half-ester, and then decarboxylated. A method is known in which alnesyl halide is condensed with acetoacetate and then deacetylated, but all of these methods have a problem in that the yield of the condensation reaction step is low, and it is necessary to start from other raw materials. Currently, there is interest in research into the production method of phalnesyl acetate.

However, according to the method of the present invention, Q-farnesyl-Q-arylsulfonylacetate can be produced from farnesyl halide in good yield, and the Q-
Since phalnesyl-Q-arylsulfonylacetate can be easily converted to phalnesyl acetate by reductive desulfonation, the industrial significance of the present invention is extremely large.

The method of the present invention can be expressed by the following reaction formula.

This reaction is carried out in the presence of a base having sufficient activity to convert the arylsulfonylacetate represented by general formula m into an anion.

Examples of suitable bases are alkali metal hydroxides (e.g. sodium hydroxide, potassium hydroxide), alkali Z metal alkoxides (e.g. sodium methoxide, sodium ethoxide, sodium n-butoxide, sodium t-butoxide).
-butoxide, potassium methoxide, potassium ethoxide, potassium t-butoxide), alkali metal phenoxides (e.g. sodium phenoxide, potassium phenoxide), alkali metal amides (e.g. potassium amide, sodium amide, lithium amide, lithium diiso) propylamide), organolithium (eg n-butyllithium), alkali metal hydrides, etc.
The amount of base to be used is sufficient to neutralize the hydrohalic acid produced by the reaction, and is usually in the range of about 1 to 2 mol per 1 mol of the compound of general formula 0, depending on the conversion rate and other selections. is suitable. The reaction ranges from about 100°C to about 150°C, depending on the raw materials used, the base and the nature of the products.
It can be carried out at temperatures ranging up to q0. Generally, when an alkali metal hydroxide or alkali metal alkoxide is used as a base, the reaction temperature is preferably about 0.000 to
The temperature is 150 qo, and lower temperatures are suitable when organic lithium, alkali metal amide, etc. are used.
Although it is possible to carry out this reaction without a solvent, it is preferably carried out in an organic solvent. Examples of organic solvents used include hydrocarbons such as n-hexane, benzene, toluene, and xylene, methanol, ethanol, propanol,
Alcohols such as butanol and bentanol, ethers such as diethyl ether, dioxane, and tetrahydrofuran, dimethylformamide, dimethylacetamide, dimethyl sulfoxide, N-methyl-pyrrolidoso,
Hexamethylphosphoramide and the like. The arylsulfonylacetate represented by the general formula m used in the method of the present invention is a known substance, and can be produced, for example, by reacting a monohalogen acetate with an alkali metal arylsulfinate.

X-CQCOORI+R hakama 02M → R2S02CQCO
ORI+ (X: halogen atom, M: alkali metal) The compound represented by the general formula 0 used in the present invention is preferably a compound having a bromine atom or a chlorine atom as X in the general formula 0.

EXAMPLES The present invention will be explained below with reference to Examples, but the present invention is not limited by these Examples.

Example 1 3.9 parts of sodium ethoxide was dissolved in 50 parts of ethanol, and 12.1 parts of ethyl P-tolylsulfonylacetate was added thereto at 0°C to carry out an anionization reaction for 1 hour. 7.5 hours of prenyl bromide was added dropwise at ~0°C, and the reaction was carried out at the same temperature for 4 hours.

After the reaction, it was neutralized with ammonium chloride, then the ethanol was removed under reduced pressure, and the residue was poured into water and extracted with ether.
Washed with water and dried. The product obtained by removing the ether is a pale yellow liquid, which was subjected to silica gel column chromatography (developing solvent: hexane/ethanol = 9/1).
) with a yield of 84% to produce Q-brenyl Q-(P
Tolylsulfonyl)ethyl acetate was obtained. The structure of Q-frenyl-Q-(P-tolylsulfonyl)ethyl acetate was confirmed as follows. Infrared absorption spectrum (nea
t) Skin-1; 1150, 1330, 1600, 1740
Nuclear magnetic resonance spectrum 6 vowel sea 14; 1.10 (t, ban), 1.55 (s, zu), 1.62 (s, insect H), 2.42 (s, thin), 2.53 ( t, ga), 3.62 (d, IH), 3.99 (q, ga), 4.87 (t, IH), 7.24 (d, general), 7,61 (d, illusion) Implementation Example 2 In the same machine as in Example 1, 50% of ethanol, 3.9% of sodium ethoxide, and 12% of ethyl P-tolylsulfonylacetate were added.
．． After reacting for 1 night, geranyl bromide 1
0.9 hours was added dropwise, and the reaction was carried out at the same temperature for 9 hours.

The reaction product was treated in the same manner as in Example 1 and purified by column chromatography to obtain Q-geranyl-(P-tolylsulfonyl)ethyl acetate in a yield of 82%. In addition, Q-geranyl-Q-(P-tolylsulfonyl)
The structure of ethyl acetate was confirmed as follows. Infrared absorption spectrum (female at) skin-1; 1150, 1330 160
0 1660, 1740 nuclear magnetic resonance spectrum 6 iso point 1
4; 1.13 (t, wide), 1.58 (s, thin), 1.6
3 (s, thin), 1.92 (s, 2H), 1.97 (s, mottled), 2.43 (s, original), 2.57 (t, mottled), 3.62 (d, IH) ), 3.99 (q, ga), 4.91 (t, bait), 7.24 (d, ga), 7.61 (d, 2H) Example 3 Potassium t-butoxide in dimethylformamide 30 After adding 12.1 liters of ethyl P-tolylsulfonylacetate at 5°C and reacting for 0.5 hours, 14.2 ml of p-tolylsulfonylacetate was added dropwise at 5 to 30°C. , and allowed to react at room temperature for 9 hours.

After the reaction, the mixture was neutralized by adding an aqueous ammonium chloride solution, concentrated under reduced pressure, poured into water, and extracted with ether. Removal of the ether gave a yellow viscous liquid as a residue, which was purified by silica gel column chromatography. The purified product obtained was ethyl Q-farnesyl-Q-(P-tolylsulfonyl)acetate, the structure of which was confirmed as shown below, and the yield was 76%. Infrared absorption spectrum (neat) skin-1; 1150, 1330
, 1600, 1740 Nuclear Magnetic Resonance Spectrum 6 Gifu 4:
1.12 (t, thin), 1. Spot (s, thin), 1.64 (s
, thin), 1.95 (s, thin), 2,40 (s, thin), 2.56 (t, 2H), 3.63 (d, IH), 3.99 (q, ga), 4 .96 (t, thin), 7. Pine (d, ga), 7.62 (d, ga) Example 4 Add 0.65 ml of sodium methoxide to 30 ml of hexamethylphosphoramide, and further add 12.1 ml of ethyl P-tolylsulfonylacetate. Thereafter, 6.9 g of solanesyl bromide was added dropwise at 1 ml, and the mixture was reacted at the same temperature for 13 hours.

After the reaction, the reaction mixture was treated in the same manner as in Example 1 to obtain a yellow viscous liquid, which was purified by silica gel column chromatography. The purified product obtained was Q-solanesyl-Q-(P-tolylsulfonyl) whose structure was confirmed as follows.
It was ethyl acetate, and the yield was 72%. Infrared absorption spectrum (fat AT) enemy-1; 1150, 1 kill
160li 16601740 nuclear magnetic resonance spectrum 8 chest d
4; 1.14 (t, ancestor), 1. Spots (s, 3 plates), 1,9
7 (s, 3), 2.43 (s, ga), 2.54 (t, 2H), 3.61 (d, IH), 4.01 (q, ga), 5.01 (broa ship , field), 7.21 (d, spot), 7.61 (d, spot) Examples 5 to 10 The following reactions were carried out in the same manner as in Example 1.

The raw materials used (0 and m), bases, reaction conditions, etc., and the results obtained are summarized in Table 1. The structure of the product was determined by infrared absorption spectrum and nuclear magnetic resonance spectrum. ship

Claims (1)

[Claims] 1 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R^1 represents a saturated or unsaturated aliphatic hydrocarbon group having 1 to 20 carbon atoms, and R^2 is phenyl or a phenyl group substituted with an alkyl group or a halogen atom, and n represents an integer of 1 to 9). 2 α・α according to claim 1, wherein in the general formula, R^1 is a lower alkyl group or a geranyl group, R^2 is a phenyl or tolyl group, and n is 3.
-Disubstituted acetate ester. 3 General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, X represents a halogen atom and n represents an integer from 1 to 9) in the presence of a base General formula R^2SO_2CH_2COOR^1 (In the formula, R^1 represents a saturated or unsaturated aliphatic hydrocarbon group having 1 to 20 carbon atoms, and R^2 represents a phenyl group or a phenyl group substituted with an alkyl group or a halogen atom.) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R^1, R^2 and n have the above meanings.)
A method for producing an α/α-disubstituted acetate shown by