JPH09143178A - Production of 4-butanolide derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To readily obtain the subject compound useful as an intermediate for a coupler for photography, by a new method for reacting a specific malonic ester with a strong base. SOLUTION: A 2-(2-acetoxyethyl)malonic ester of formula I (R<1> is a <=6C alkyl; R<2> is a <=13C alkyl or aromatic hydrocarbon) is reacted with a strong base (preferably sodium hydride) to give the objective compound of formula II. The reaction is preferably carried out in an aprotic polar solvent such as dimethylformamide at a room temperature to 60 deg.C. For example, 2- acetoxyethyl-2-ethylamlonic acid diethyl ester may be cited as the compound of formula I. The compound of formula I, for example, is obtained by reacting a compound of formula III such as diethyl malonate with a compound of the formula, R<2> -X<1> (X<1> is Cl, I, etc.) such as ethyl iodide in the presence of a base and reacting the reaction product with a compound of the formula, CH3 COOCH2 CH2 -X<2> (X<2> is X<1> ) such as chloroethyl acetate.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel method for producing a 2- (2-alkoxycarbonylacetyl) -4-butanolide derivative useful as a photographic coupler intermediate.

[0002]

2. Description of the Related Art 3-Cyclopropyl-3-oxopropionic acid anilide is known as a photographic coupler (Japanese Patent Laid-Open No. 4-218,042). However, the production method is unsatisfactory in production suitability because a high temperature is required when forming a three-membered ring by the ring contraction method. As a method for producing the coupler, 2- (2-anilinocarbonylacetyl) -4 is used.
-The ring reduction method of butanolide (Japanese Patent Application Laid-Open No. 7-70,100) is preferable in that the reaction proceeds at a lower temperature, but the intermediate 2- (2-alkoxycarbonylacetyl) -4-butanolide is produced. It took many steps and was not convenient.

[0003]

SUMMARY OF THE INVENTION It is therefore an object of the present invention to provide a new process for preparing 2- (2-alkoxycarbonylacetyl) -4-butanolides useful as photographic coupler intermediates.

[0004]

The object of the present invention is to react 2- (2-acetoxyethyl) malonic acid esters represented by the following general formula (A) with a strong base. This was achieved by the method for producing a 2- (2-alkoxycarbonylacetyl) -4-butanolide derivative represented by the formula (B).

[0005]

Embedded image

(In the formula, R ¹ represents an alkyl group having 6 or less carbon atoms, R ² represents an alkyl group having 13 or less carbon atoms, or an aromatic hydrocarbon group.)

[0007]

Embedded image

(In the formula, R ¹ represents an alkyl group having 6 or less carbon atoms, R ² represents an alkyl group having 13 or less carbon atoms, or an aromatic hydrocarbon group.)

[0009]

Next, the present invention will be described in detail. The compound represented by formula (A) used in the present invention will be described. The alkyl group represented by R ¹ is an alkyl group having 6 or less carbon atoms, preferably an alkyl group having 3 or less carbon atoms such as a methyl group, an ethyl group and a propyl group, and particularly preferably a methyl group or an ethyl group. The alkyl group represented by R ² is an alkyl group having 13 or less carbon atoms and may be substituted with an unsaturated hydrocarbon group such as an allyl group or a benzyl group. As such an alkyl group, an alkyl group having 7 or less carbon atoms such as a methyl group, an ethyl group, a propyl group, an allyl group and a benzyl group is preferable, and an ethyl group is particularly preferable.

The aromatic hydrocarbon group represented by R ² is an aromatic hydrocarbon group having 13 or less carbon atoms, preferably a phenyl group or a naphthyl group, most preferably a phenyl group. These aromatic hydrocarbon groups may be further substituted. As such a substituent, an alkoxy group having 3 or less carbon atoms such as a methoxy group and an ethoxy group, a halogen atom, and a nitro group are preferable. Of the substituents represented by R ² , the ethyl group is most preferable.

The substituents R ¹ and R ² of the compound represented by the general formula (B) used in the present invention have the same meanings as those of the compound represented by the general formula (A). General formula (A) used in the present invention
The compound can be synthesized by the following formula (1) or formula (2).

[0012]

Embedded image

[0013]

[Chemical 6]

X ¹ and X ² represent a leaving group in which the pKa of the conjugate acid is 4 or less, and among them, a chlorine atom, a bromine atom, an iodine atom, or an alkylsulfonic acid group or an arylsulfonic acid group is preferable. Of these, a bromine atom, an iodine atom, a methanesulfonic acid group, a benzenesulfonic acid group, and a toluenesulfonic acid group are particularly preferable.

Base 1, base 2, base 3 and base 4 represent bases having a conjugate acid pKa of 12 or more. Among them, alcoholates such as sodium methylate, sodium ethylate and tetramethylammonium methylate, hydrogen. Metal hydrides such as sodium hydride and metal hydroxides such as potassium hydroxide are preferred.

The reaction solvent may be a polar solvent or a non-polar solvent, but alcohols such as methanol and ethanol, dimethylformamide (DMF), dimethylsulfoxide (DMSO), dimethylimidazole (D
Aprotic polar solvents such as MI) and ethers such as tetrahydrofuran (THF) are preferable, and aprotic polar solvents such as DMF, DMSO and DMI are particularly preferable. In the reaction, an iodide salt can be used as a catalyst. The amount is 1 mol% to 1 with respect to the substrate
00 mol% is preferable and 5 mol% to 100 mol
% Is particularly preferred. Potassium iodide as iodide salt,
Most preferred is sodium iodide. The reaction temperature is usually
Room temperature to 120 ° C, preferably 70 ° C to 110 ° C.

The compound represented by the general formula (A) can be derived in one step from the compound represented by the general formula (B) as shown in the formula (3). The reaction mechanism is considered to be that the 7-membered ring lactone produced by intramolecular Claisen condensation is isomerized to a more stable 5-membered ring lactone as shown in the formula (4).

[0018]

Embedded image

[0019]

Embedded image

The base 5 is not particularly limited as long as it is a strong base capable of dissociating the proton of the acetyl group, but among these strong bases, sodium hydride is particularly preferable. The solvent is ethers such as THF, or DMF
Aprotic polar solvents such as DMSO and DMSO are preferred. The reaction temperature is preferably room temperature to 100 ° C, room temperature to 60 ° C
Is particularly preferred. Next, specific examples of the compounds represented by formulas (A) and (B) of the present invention are shown.

[0021]

Embedded image

[0022]

Embedded image

[0023]

Next, the present invention will be described in more detail by way of examples. [Synthesis of diethyl 2-acetoxyethyl-2-ethylmalonate (Compound A-2)] 60% sodium hydride 8.
8 g (0.22 mol) was washed twice with 20 ml of hexane to remove mineral oil. 150 ml of DMF was added, and 32.0 g (0.20 mol) of diethyl malonate was added dropwise under ice cooling. After the generation of hydrogen gas stopped, 31.2 g (0.20 mol) of ethyl iodide was added, and the mixture was stirred at 50 ° C. for 6 hours. 8.8 g (0.22) of 60% sodium hydride
(mol) was washed twice with 20 ml of hexane to remove mineral oil. After the above reaction liquid was added to this and the generation of hydrogen gas stopped, 27.0 g (0.22 mo) of chloroethyl acetate was added.
1) was added, and the mixture was stirred at 90 ° C. for 5 hours. After completion of the reaction, the temperature was returned to room temperature, and the mixture was poured into 500 ml of ice-cold 0.2N hydrochloric acid.
Extracted twice with 200 ml of ethyl acetate and the organic layer was 0.5
It was washed successively with aqueous sodium hydroxide N, 0.5N hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine. The organic layer was dried over anhydrous sodium sulfate, the solvent was removed, and the residue was further purified by vacuum distillation. bp (0.35 mmHg) 100 ° C to 105 ° C.
Yield 31.4 g (57%).

1H NMR (300 MHz, δ ppm, in
CDCl3) 4.21 (2H, q, J = 7.2Hz), 4.19 (2
H, q, J = 7.2 Hz), 4.10 (2H, t, J =
6.6 Hz), 2.26 (2H, t, J = 6.6H)
z), 2.01 (3H, s), 1.97 (2H, q, J
= 7.5 Hz), 1.26 (6H, t, J = 7.2H)
z), 0.85 (3H, t, J = 7.5Hz)

[Synthesis of dimethyl 2-acetoxyethyl-2-ethylmalonate (Compound A-3)] 33.6 g (0.84 mol) of 60% sodium hydride was washed twice with 40 ml of hexane to remove mineral oil. . DMF 600 ml
Then, 106 g of dimethyl malonate (0.80
mol) was added dropwise. After the generation of hydrogen gas stopped, 119.9 g (0.80 mol) of sodium iodide and 98 g (0.80 mol) of chloroethyl acetate were added, and the temperature was changed to 80 ° C.
For 5 hours. 60% sodium hydride 33.6
g (0.84 mol) was washed twice with 40 ml of hexane to remove mineral oil. After the reaction liquid was added to this and the generation of hydrogen gas subsided, 131 g (0.8 g) of ethyl iodide was added.
4 mol) was added, and the mixture was stirred and refluxed at 90 ° C. for 5 hours. After the reaction was completed, the temperature was returned to room temperature and ice-cooled 0.2N hydrochloric acid 1500 m
poured into l. The mixture was extracted 3 times with 500 ml of ethyl acetate, and the organic layer was washed successively with 0.5N aqueous sodium hydroxide, 0.5N hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine. The organic layer was dried over anhydrous sodium sulfate, the solvent was removed, and the residue was further purified by vacuum distillation. bp (0.35mmHg) 105 ℃
~ 110 ° C. Yield 134 g (61%).

1H NMR (300 MHz, δ ppm, in
CDCl3) 4.10 (2H, t, J = 6.6Hz), 3.74 (6
H, s), 2.26 (2H, t, J = 6.6 Hz),
2.01 (3H, s), 1.97 (2H, q, J = 7.
5Hz), 0.85 (3H, t, J = 7.5Hz)

Example 1 [2-Ethyl-2-ethoxycarbonylacetyl-4-
Synthesis of butanolide (Compound B-2)] 0.88 g (22 mmol) of 60% sodium hydride was washed twice with 4 ml of hexane to remove mineral oil. Add 25 ml of DMF,
A solution of 5.5 g (20 mmol) of diethyl 2-acetoxyethyl-2-ethylmalonate and 5 ml of DMF was added dropwise. After completion of the dropping, the mixture was heated to 55 ° C. and stirred for 3 hours.
After the generation of hydrogen gas was stopped, the temperature was returned to room temperature and the mixture was poured into 100 ml of ice-cooled water. After washing with 20 ml of ethyl acetate, the pH was adjusted to 2 with 6N hydrochloric acid, and the mixture was extracted twice with 30 ml of ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography to obtain 2.77 g (61%) of the desired lactone.
The various spectra of this product were in perfect agreement with the standard.

Example 2 [2-methoxycarbonylacetyl-2-benzyl-4]
-Synthesis of butanolide (Compound B-5)] 0.88 g (22 mmol) of 60% sodium hydride was washed twice with 4 ml of hexane to remove mineral oil. 25 ml of DMSO was added, and a solution of 6.2 g (20 mmol) of dimethyl 2-acetoxyethyl-2-benzylmalonate and 5 ml of DMSO was added dropwise while maintaining the temperature of the reaction solution at 30 ° C. After the completion of dropping, the mixture was stirred at 30 ° C. for 2 hours. After the generation of hydrogen gas ceased, it was poured into 100 ml of ice-cooled water. 20
After washing with ml of ethyl acetate, the pH was adjusted to 2 with 6N hydrochloric acid, and the mixture was extracted twice with 30 ml of ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue is purified by silica gel column chromatography to obtain the desired lactone 3.
1 g (56%) was obtained. The various spectra of this product were in perfect agreement with the standard.

[0029]

INDUSTRIAL APPLICABILITY The 4-butanolide derivative can be easily produced by reacting a malonic acid ester compound with a strong base.

Claims (1)

[Claims] 1. 2- (2-represented by the following general formula (A):
(2) represented by the following general formula (B), characterized in that acetoxyethyl) malonic acid esters are reacted with a strong base.
A method for producing a-(2-alkoxycarbonylacetyl) -4-butanolide derivative. Embedded image (In the formula, R ¹ represents an alkyl group having 6 or less carbon atoms, R ² represents an alkyl group having 13 or less carbon atoms, or an aromatic hydrocarbon group.) (In the formula, R ¹ represents an alkyl group having 6 or less carbon atoms, R ² represents an alkyl group having 13 or less carbon atoms, or an aromatic hydrocarbon group.)