JPH10182523A - Production of 1-substituted-2,2-difluoro-3-butene-1-ol - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce a 1-substituted-2,2-difluoro-3-butene-1-ol in high yield under a mild condition by making aldehydes react with 3-bromo-3,3-difluoropropane in the presence of indium. SOLUTION: This production of a 1-substituted-2,2-difluoro-3-butene-1-ol comprises making an aldehyde of the formula (R<1> , R<2> , R<3> and R<4> are each an alkyl or aryl) react with 3-bromo-3,3-dichloropropene at room temperature or under a mild condition near to the room temperature in the presence of indium in nitrogen atmosphere by using dimethylformamide as a solvent, thereafter adding hydrochloric acid to the reaction system, subjecting the reactant to ether extraction, washing the liquid extract with a saturated sodium chloride solution, drying the extract with anhydrous magnesium sulfate, distilling the solvent off, and purifying the extract by silica gel column chromatography.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a process for producing 1-substituted-2,2-difluoro-3-buten-1-ols.

[0002]

2. Description of the Related Art Due to its unique properties, fluorine-containing compounds have been spotlighted in various fields such as material science and pharmaceuticals, and various fluorination reactions and the development of fluorine-containing synthetic elements for constructing fluorine-containing compounds have been developed. It is being actively conducted. 1-substituted-2,2-difluoro-3-butene-1
-Alls are compounds that can be expected to be used as fluorine-containing synthesis elements. Conventional 1-substituted-2,2-difluoro-3
The production of -buten-1-ols involves the production of aldehydes and 3-butene-1-ols.
It has been carried out by reacting a bromo-3,3-difluoropropene derivative in the presence of n-butyllithium or zinc.

[0003]

The conventional 1-position substitution-2,
The method for producing 2-difluoro-3-buten-1-ols, in which an aldehyde compound and a 3-bromo-3,3-difluoropropene compound are reacted in the presence of n-butyllithium, is -95 ° C. In addition, there is a disadvantage that the reaction of n-butyllithium to the carbonyl group occurs as a side reaction, and the yield is not always good. The method of reacting an aldehyde compound with a 3-bromo-3,3-difluoropropene compound in the presence of zinc has the advantage of being able to be carried out at room temperature, but has the advantage of being substituted at the 1-position, 2,2-difluoro-3-. The yield of buten-1-ols is not so high as 75 to 47%, and a new 1-substitution is obtained.
A method for synthesizing 2,2-difluoro-3-buten-1-ols has been desired. An object of the present invention is to provide a method for producing 1-substituted-2,2-difluoro-3-buten-1-ols at room temperature or a temperature close thereto at a high yield.

[0004]

According to the present invention, there is provided a compound of the general formula

[0005]

(Wherein, R ¹ represents a carbon functional group such as an alkyl group or an aryl group. In the formula, R ² , R ³ and R ⁴ may be the same or different, and have an internal bond. And an aldehyde compound represented by a carbon functional group such as an alkyl group and an aryl group.
1-substituted-2,2-difluoro-3-characterized by reacting a difluoropropene compound in the presence of indium.
The present invention relates to a method for producing buten-1-ols. Next, the method of the present invention will be described. As the raw material of the present invention, a general formula

[0006]

Embedded image (Wherein, R ¹ represents a carbon functional group such as an alkyl group or an aryl group);

[0007]

Embedded image (Wherein, R ² , R ³ and R ⁴ may be the same or different and may be bonded to each other, and represent a carbon functional group such as an alkyl group and an aryl group). Bromo-3,3-difluoropropene, and indium. General formula

[0008]

Embedded image (In the formula, R ¹ represents a carbon functional group such as an alkyl group and an aryl group. In the formula, R ² , R ³ and R ⁴ may be the same or different, and may be internally bonded;
Represents a carbon functional group such as an alkyl group and an aryl group. ) Represents a carbon functional group such as an alkyl group and an aryl group which may be bonded. The reaction of the aldehyde compound and the 3-bromo-3,3-difluoropropene compound in the presence of indium represented by the formula (1) is carried out in a solvent. Any solvent can be used as long as it does not participate in the reaction. Solvents that do not participate in the reaction include dimethylformamide, acetonitrile, propiononitrile, nitroethane, nitromethane, aprotic polar solvents such as dimethylsulfoxide, ether, dioxane,
Diglyme, 1,2-dimethoxyethane, ether solvents such as tetrahydrofuran, water, methanol, ethanol, protic polar solvents such as isopropanol, benzene, toluene, aromatic solvents such as xylene, hexane,
Alkyl solvents such as cyclohexane and pentane are used, and these are used alone or as a mixed solvent. Preferably, dimethylformamide is used as the sole solvent. The amounts of the aldehyde, 3-bromo-3,3-difluoropropene and indium to be used are not particularly limited, but the amount of the 3-bromo-3,3-difluoropropene is usually 1.5 to 1.5 parts of the aldehyde. Molar equivalent, indium 1.5
It is preferred to use molar equivalents. The reaction proceeds smoothly from -100 ° C to 100 ° C.

[0009]

The present invention will be described in detail with reference to the following examples, but it goes without saying that the present invention is not limited to these examples.

[00010]

Embodiment 1

[0011]

Embedded image Indium (86 mg, 0.75 m
mol) and 3-bromo-3,3-difluoropropene (76 μl, 0.75 mmol) in dimethylformamide (5 ml) were added to a solution of (E) -hept-2-enal (6
5 μl, 0.50 mmol) and stir for 3 hours. 10
% Hydrochloric acid (5 ml) was added, and the mixture was extracted three times with ether (30 ml). The extract was washed with saturated saline (30 ml), dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 30: 1) to obtain the desired compound (E). ) -3,3-
Difluorodeca-1,5-dien-4-ol (94 m
g, 99% yield).

IR (neat, cm ^-1 ): 3404. ¹ H-NMR (CDCl ₃ ) δ: 0.89 (3H, t,
J = 7.1 Hz), 1.25-1.43 (4H, m),
2.03-2.12 (3H, m), 4.24-4.27
(1H, br), 5.43-5.48 (1H, m),
5.53 (1H, d, J = 11.5 Hz), 5.70
(1H, dd, J = 19.8, 2.2 Hz), 5.84
-6.04 (2H, m). ¹⁹ F-NMR (CDCl ₃ ) δ: -139.7 (d
t, J = 249 and 10 Hz, 1F), -111.
7 (dt, J = 249 and 12 Hz, 1F) MS m / z: 190 (M ^<+> ).

[0013]

Embodiment 2

[0014]

Embedded image Indium (86 mg, 0.75 m
mol) and 3-bromo-3,3-difluoropropene (76 μl, 0.75 mmol) in dimethylformamide (5 ml).
mg, 0.50 mmol) and stirred for 3 hours. 10%
Hydrochloric acid (5 ml) is added, and the mixture is extracted three times with ether (30 ml). The extract was washed with saturated saline (30 ml), dried over anhydrous magnesium sulfate, evaporated, and purified by silica gel column chromatography (n-hexane: ethyl acetate = 30: 1) to obtain the desired 1- (4-Bromophenyl) -2,2-difluoro-3-buten-1-ol (124 mg, yield 95%) is obtained.

IR (neat, cm ^-1 ): 3420. ¹ H-NMR (CDCl ₃ ) δ: 2.53-2.63
(1H, br), 4.88 (1H, t, J = 9.6H)
z), 5.48 (1H, d, J = 11.0 Hz), 5.
57 (1H, d, J = 18.1 Hz), 5.74-5.
91 (1H, m), 7.29 (2H, d, J = 8.2H
z), 7.49 (2H, d, J = 8.2 Hz). ¹⁹ F-NMR (CDCl ₃ ) δ: −107.8 (d
t, J = 246 and 10 Hz, 1F), -111.
7 (dt, J = 246 and 9.8 Hz, 1F) MS m / z: 262 (M ⁺ ).

[0016]

Embodiment 3

[0017]

Embedded image Indium (172 mg, 1.5 m
mol) and 3-bromo-3,3-difluoropropene (152 μl, 1.50 mmol) in dimethylformamide (5 ml).
1.0 mmol) and stirred for 3 hours. 10% hydrochloric acid (5
ml) and extract three times with ether (30 ml).
The extract was washed with saturated saline (30 ml), dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was subjected to silica gel column chromatography (n-hexane: ethyl acetate = 3).
0: 1) to give the desired 2,2-difluoro-1-phenyl-3-buten-1-ol (182 mg, yield 99).
%).

IR (neat, cm ^-1 ): 3424. ¹ H-NMR (CDCl ₃ ) δ: 3.13-3.16
(1H, br), 4.87 (1H, t, J = 9.3H)
z), 5.46 (1H, d, J = 11.0 Hz), 5.
60 (1H, d, J = 17.6 Hz), 5.78-5.
95 (1H, m), 7.36-7.43 (5H, m). ¹⁹ F-NMR (CDCl ₃ ) δ: -107.9 (d
t, J = 246 and 9.9 Hz, 1F), -11
0.1 (dt, J = 246 and 12.4 Hz, 1
F) MS m / z: 253 (M ⁺ ).

[0019]

According to the present invention, 1-substituted-2,2-difluoro-3-buten-1-ols can be efficiently produced under mild conditions.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Yusho Momose 2556, Gofuku, Toyama 4 (72) Inventor Masayuki Kirihara 1-1127-702, Meiwa-cho, Toyama-shi (72) Inventor Tomofumi Tatewa Toyama 62-3 Shimono, Shimono, Fontine Emi 203 (72) Inventor Shinobu Takizawa 352 Furusawa, Toyama City

Claims (1)

[Claims] 1. The following general formula: (In the formula, R ¹ represents a carbon functional group such as an alkyl group and an aryl group. In the formula, R ² , R ³ and R ⁴ may be the same or different, and may be internally bonded;
Represents a carbon functional group such as an alkyl group and an aryl group. 1) -substituted-2,2-difluoro-3-butene-characterized by reacting an aldehyde compound and a 3-bromo-3,3-difluoropropene compound represented by the formula (1) in the presence of indium.
The present invention relates to a method for producing 1-ols.