JPH0672958A - Production of trans-beta-acylacrylic ester derivative - Google Patents

Abstract

PURPOSE:To easily obtain in high yield the subject compound useful as an intermediate for pesticides and medicines by reaction of a specific ester with a ketone in the presence of a phase-transfer catalyst and an acid scavenger. CONSTITUTION:The objective compound of formula III can be obtained by reaction of (A) a compound of formula I (Z is alkyl) (e.g. methyl-fluorosulfonyl acetate) with (B) a compound of formula II [R is alkyl, cycloalkyl, (substituted) phenyl, (substituted) phenylalkyl, (substituted) phenylalkenyl, heteroaryl or condensed aromatic ring] (e.g. phenacyl bromide) in the presence of (C) a phase- transfer catalyst (e.g. dimethylammonium benzyl chloride) and (D) an acid scavenger (e.g. sodium bicarbonate, triethylamine).

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel method for producing a trans β-acylacrylic acid derivative.

[0002]

2. Description of the Related Art A method for reacting phenylmethanesulfonyl fluoride with aldehydes or ketones is described in Reference J. C
hem. Soc. Chem. Commun. , 199
1-Page 408, β-benzoylacrylic acid is a Friedel-Craftsa acylation reaction of benzene and maleic anhydride.
Cylation) or a known reaction such as a dehydration reaction of glyoxylic acid and acetophenone.

[0003]

The trans β-acylacrylic acid derivative is useful as a pesticide or an intermediate for the production of pharmaceuticals and pesticides. The present application provides a novel method for producing the compound.

The trans β-acyl acrylic acid derivative represented by the following formula (I) is

[Chemical 4] In the formula, Z is alkyl, R is alkyl, cycloalkyl, optionally substituted phenyl, optionally substituted phenylalkyl, optionally substituted phenylalkenyl, heteroaryl, and fused aromatic ring. The manufacturing method of the present invention, which is represented by formula (II):

[Chemical 5] In the formula, Z is a compound represented by the formula (II
I):

[Chemical 6] In the formula, R can be produced by reacting with the compound represented by the same as above in the presence of a phase transfer catalyst and an acid binder.

According to the manufacturing method of the present invention, the conventional method,
For example, it has the following advantages over the method. Since the reaction conditions are mild, condensation of the starting ketones can be prevented and the yield is good. Since the reaction operation is simple, it is not necessary to set special equipment or strict conditions for temperature. Only the trans form can be selectively synthesized. In the above production method, when ethyl fluorosulfonyl acetate and phenacyl bromide are used as raw materials, for example, they are represented by the following reaction formulas.

[Chemical 7]

In the compounds of formula (I), preferably
Z represents a linear or branched alkyl group having 1 to 4 carbon atoms, and R represents a linear or branched alkyl group having 1 to 4 carbon atoms, or 3 to 7 carbon atoms. Represents a cycloalkyl of, or is halogen, nitro, cyano, or 1 to 1 carbon atoms.
2 represents phenyl which may be substituted by alkyl having 2 or alkoxy having 1 to 2 carbon atoms, or phenyl represents halogen, nitro, cyano, alkyl having 1 to 2 carbon atoms or 1 to 2 carbon atoms and halogen atoms The alkyl part optionally substituted by 1 to 5 haloalkyl represents phenylalkyl having 1 to 2 carbon atoms, or phenyl represents halogen, nitro, cyano, 1 to 1 carbon atom
The alkyl moiety which may be substituted with 2 alkyl or 1 to 2 carbon atom and 1 to 5 halogen atom haloalkyl represents phenylalkenyl having 2 to 4 carbon atoms, or represents thienyl, furyl or naphthyl. Particularly preferably, Z represents methyl or ethyl, R
Represents t-butyl, isopropyl, ethyl, methyl, or phenyl which may be mono- or di-substituted by a substituent selected from a fluorine atom, a chlorine atom, nitro, cyano, methyl or methoxy. , Or
Cyclohexane, benzyl, cinnamoyl, thienyl,
Indicates ruffle and naphthyl.

In the starting compound of the formula (II), Z
Has the same meaning as defined above, preferably the same meaning as defined above. The compound of formula (II) can be synthesized, for example, by reacting chlorosulfonyl acetate and anhydrous potassium fluoride in dry acetonitrile in the presence of crown ether, and specific examples thereof include the following compounds. it can. Methyl fluorosulfonyl acetate, ethyl fluorosulfonyl acetate.

In the compound of the formula (III) which is another starting material, R has the same meaning as defined above, preferably the same meaning as defined above for R. The compound of formula (III) is a compound well known in the field of organic chemistry, and specific examples thereof include the following compounds. Phenacyl bromide, 4-chlorophenacyl bromide, 4-bromophenacyl bromide, 4-nitrophenacyl bromide,
4-methoxyphenacyl bromide, 4-methylphenacyl bromide, 4-fluorophenacyl bromide,
And 3,4-dichlorophenacyl bromide.

In the practice of the present invention, suitable diluents include all inert organic solvents. Examples of such diluents include aliphatic, cycloaliphatic and aromatic hydrocarbons (which may optionally be chlorinated) such as pentane, hexane, cyclohexane, petroleum ether, ligroin, benzene, toluene, xylene. , Methylene chloride, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, ethylene chloride, chlorobenzene, dichlorobenzene; other ethers such as ethyl ether, methyl ethyl ether, isopropyl ether, butyl ether, propylene oxide, dioxane, Dimethoxyethane (DME), anisole, tetrahydrofuran (TH
F), diethylene glycol dimethyl ether (DG
M), diethylene glycol diethyl ether; other ketones such as acetone, methyl ethyl ketone (M
EK), methyl-iso-propyl ketone, methyl-iso-butyl ketone (MIBK); other, nitriles such as acetonitrile, propionitrile, acrylonitrile, benzonitrile; other, esters such as ethyl acetate, amyl acetate; other, Acid amides such as dimethylformamide (DMF) and dimethylacetamide (DMA); other sulfones and sulfoxides such as dimethylsulfoxide (DMSO) and sulfolane;
Other examples include bases such as pyridine.

In the process of the present invention, as the phase transfer catalyst, tetraalkylammonium halide, tetraalkylphosphonium halide, crown ethers or cryptands such as benzyldimethylammonium chloride, benzyltributylammonium bromide and benzyl chloride are used. Tributylammonium, cetylbenzyldimethylammonium chloride, cetylbenzyldimethylammonium bromide, dodecyltrimethylammonium chloride,
Tetrabutylammonium chloride, tetrabutylammonium iodide, triethylbenzylammonium chloride, triethylbenzylammonium bromide, 18-crown-
6-ether, dibenzo-18-crown-6, dibenzo-24-crown-8-ether, dicyclohexano-18-crown-6-ether and the like can be mentioned.

The production method of the present invention is carried out in the presence of an acid binder, and examples of such an acid binder include alkali metal hydroxides, carbonates, bicarbonates and alcoholates as inorganic bases such as sodium hydrogen carbonate. Examples thereof include potassium acetate, sodium acetate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, magnesium carbonate, calcium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide and calcium hydride.
Tertiary amines, dialkylaminoanilines and pyridines as organic bases such as triethylamine, tributylamine, 1,1,4,4-tetramethylethylenediamine (TMEDA), N, N-dimethylaniline, N, N- Diethylaniline, pyridine, 4-dimethylaminopyridine (DMAP), 1,4-diazabicyclo [2,2,2] octane (DABCO) and 1,8-
Diazabicyclo [5,4,0] undec-7-ene (D
BU) and the like.

The method of the present invention can be carried out within a substantially wide temperature range. Generally, about 0 to about 1
It can be carried out at 50 ° C, preferably between about 0 and about 100 ° C. Further, although it is desirable to carry out the reaction under normal pressure,
It is also possible to operate under pressure or reduced pressure. In carrying out the present invention, it can be carried out in a substantially wide molar ratio, but generally 0.5 mol to 3 mol, preferably 1 mol of the compound of the formula (II), 0.8
The target compound can be obtained by reacting a molar amount to 1.2 molar amount of the formula (III). The amount of the acid binder used in the production method of the present invention can be carried out in a substantially wide range, but in general, 1 mol to 6 mol per 1 mol of the compound of the formula (II) is used. Preferably, 2 to 3 molar amount is used. The amount of the phase transfer catalyst used in the production method of the present invention is the same as the amount of the catalyst generally used in organic chemistry, and for example, 0.001 mol to 0 mol per 1 mol of the compound of the formula (II). 0.01 molar amount is used.

The trans β-produced according to the invention
The acylacrylic acid derivative is useful, for example, as a miticide (JP-A-56127302) and is also used as an intermediate for the production of compounds expected as a diuretic / antihypertensive agent (JP-A-59). 29606, JP-A-61
No. 61995, JP-A No. 17895, 61, JP-A No. 6
227594 for 1 year, 129260 for 1987 and 104034 for 1 year). Hereinafter, the content of the present invention will be specifically described with reference to Examples, but the present invention should not be limited thereto.

[0014]

【Example】

 Synthesis example 1

[Chemical 8] 450 mg of ethyl fluorosulfonyl acetate and 497 mg of phenacyl bromide were dissolved in 10 ml of acetonitrile, to which a catalytic amount of dibenzo-18-crown-6 (about 500 mg) was added. After adding 3.6 g of anhydrous powdered potassium carbonate while stirring the mixture, 24
Stir at room temperature for hours. The reaction solution was passed through a short column (silica gel) to separate the benzene outflow fraction, and benzene was distilled off to obtain an oily crude product. This crude product was distilled under reduced pressure to obtain 134 mg of ethylbenzoyl acrylate. Boiling point 165-175 ° C./15 mmHg Compounds synthesized in the same manner as in Synthesis Example 1 are shown in Table 1 below.

[0015]

[Table 1]

[0016]

According to the production method of the present invention, trans β
-Acyl acrylic acid derivative can be selectively and easily produced in good yield.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI Technical display location C07C 69/653 9279-4H 69/736 9279-4H 201/12 205/56 7188-4H C07D 307 / 54 333/24 // C07B 61/00 300

Claims (4)

[Claims] 1. The formula: In the formula, Z is alkyl, R is alkyl, cycloalkyl, optionally substituted phenyl, optionally substituted phenylalkyl,
A method for selectively producing a trans isomer of a β-acylacrylic acid derivative represented by an optionally substituted phenylalkenyl, a heteroaryl, or a condensed aromatic ring, which is represented by the formula (II): 2] In the formula, Z is a compound represented by the same as above, and a compound of the formula (III): In the formula, R is the same as described above, and is reacted in the presence of a phase transfer catalyst and an acid binder. 2. Z represents a straight-chain or branched alkyl having 1 to 4 carbon atoms, R represents a straight-chain or branched alkyl having 1 to 4 carbon atoms, or Represents a cycloalkyl having 3 to 7 carbon atoms, or halogen, nitro, cyano, or 1 to 2 carbon atoms
Of alkyl or phenyl optionally substituted by alkoxy having 1 to 2 carbons, or phenyl is halogen, nitro, cyano, alkyl having 1 to 2 carbons or 1 to 2 carbons, and 1 halogen atom. The alkyl moiety optionally substituted by haloalkyl of -5 represents phenylalkyl having 1 to 2 carbon atoms, or
Phenyl is halogen, nitro, cyano, alkyl having 1 to 2 carbons or 1 to 2 carbons and 1 to 1 halogen atom.
The alkyl moiety optionally substituted by haloalkyl of 5 represents phenylalkenyl having 2 to 4 carbon atoms,
Alternatively, it represents thienyl, furyl, or naphthyl.
A method for producing the described trans β-acyl acrylic acid derivative. 3. Z represents methyl or ethyl, R represents t-butyl, isopropyl, ethyl, methyl, or a fluorine atom, chlorine atom, nitro, cyano,
The trans β-acyl acryl according to claim 1, which represents phenyl which may be mono- or di-substituted with a substituent selected from methyl or methoxy, or represents cyclohexane, benzyl, cinnamoyl, thienyl, furyl or naphthyl. Method for producing acid derivative. 4. The phase transfer catalyst is 18-crown-6-
Ether, dibenzo-18-crown-6, dibenzo-
The method for producing a trans β-acylacrylic acid derivative according to claim 1, 2 or 3, which is selected from 24-crown-8-ether and dicyclohexano-18-crown-6-ether.