JPS6056693B2 - Method for producing halogenated propionic acid derivatives - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a halogenated propionic acid derivative, and more particularly to a method for producing a halogenated propionic acid derivative, which is characterized by adding a halogen to an acrylic acid halide.

General formula: a■'■CFCOY (1) (In the formula, X' represents a halogen, and Y represents a hydroxy group, an alkoxy group, or an amino group.

) are useful as synthetic intermediates for pharmaceuticals and the like.

Compound (1) has the general formula: CH2X'CFX''COY (
2) (In the formula, Y has the same meaning as above.

X' and x'' represent the same or different halogens.
) can be easily obtained by eliminating C from the compound (2), and the production method of the present invention provides an easy production method for this compound (2).

The manufacturing method of the present invention is based on the general formula: CH9=CFC0X(3) (In the formula, X represents halogen.

) to the acrylic acid halide shown in General formula: X’X″ (4) (In the formula, X' and x'' have the same meanings as above.

) by adding a halogen compound represented by the general formula: CH
2X'CFX''COX (5) (wherein X, X' and x
″ has the same meaning as above.

) is obtained, and then, if necessary, this compound is reacted with water, alcohol or ammonia to obtain the general formula:
CH2X′CFX℃0Y(2) (wherein, Y, X″ and x″ have the same meanings as above.

). When producing the target compound (2) of the present invention, the commonly considered methods are:
Known general formula: (wherein, Y has the same meaning as above.

) is a method in which a halogen compound (4) is added to the compound represented by (), but in this method, the compound (7) tends to polymerize, so it is difficult to obtain the target compound (2) in a good yield.

However, according to the process of the present invention, a compound that is easy to polymerize (
It is advantageous that the target compound (2) can be synthesized without using 7).

The starting material acrylic acid halide (3) is obtained, for example, by treating 2,2,3,3-tetrafluorooxetane with sodium iodide and zinc.

Acrylic acid halide (3) and halogen compound (4)
The reaction is preferably carried out in an inert organic solvent (e.g., carbon tetrachloride, chloroform, acetonitrile, glymes such as tetraglyme, perfluoroalkane, etc.) at a temperature of 0 to 100°C, preferably 30 to 50°C. Let's do it.

Compound (5) may be converted to compound (2) according to known methods.

Typically, water, alcohol (e.g., lower monoalcohols such as methanol, ethanol, etc.) or ammonia are added to 0
The compound (
5). The resulting compound (5) or (2) is removed from the reaction mixture by conventional methods such as distillation, evaporation to dryness, etc. It can be recovered.

Next, the manufacturing method of the present invention will be explained in detail by showing Examples and Comparative Examples.

Note that the yield was determined based on the raw material acrylic acid halide. Example 1 (1) CH2=CFCO in a 500 m four-bottle flask
FlOOy (1.087 mol) of carbon tetrachloride 300 ml
Bromine 191y (1.194 mol) was slowly added dropwise to the solution at 20-35°C.

After the dropwise addition, the solvent was distilled off under reduced pressure to obtain crude CH2BrCF.
BrCOF26l9 was obtained. GC-MS: 195 (M+
-COF), 163 (M+-Br), 93 (CH2Br
). Excess ethanol (approximately 100 fI) was added dropwise to the remaining concentrate at 20-35°C. The reaction mixture was washed with water, separated and dried over magnesium sulfate to give crude CH2BrCFBr.
COOC2H5352f was obtained.

This was distilled under reduced pressure to obtain pure product 267f (0.960 mol). Yield 88.3%. 0-MS: 276 (M+), 1
97 (M+-Br), 93 (CH2Br), 29 (C2
H5).

2) Next, 400 ml of dichloromethane was added to the reaction mixture obtained in (1), and 1,8-diazabicyclo[5.4.
0] Undecene-7150y (0.987 mol) 20
It was added dropwise at ~35°C.

After the dropwise addition was completed, the solution was washed with 1N hydrochloric acid, water, 1N sodium carbonate, and water in this order. Next, the solvent was distilled off under reduced pressure, and the residue was further distilled under reduced pressure to obtain CHBr=CFCOOC2H5.
l64y (0.832 mol) was obtained. Yield 76.6%,
Boiling point 73-800C/26H'. Seven Comparative Example 1 1) In a 500 ml four-loop flask, CH2=CFCOFlOOf(1.0
87 mol) was added dropwise.

At this stage, some polymerization occurred to form a rubbery substance. 2) Next, after removing the rubbery substance from the reaction mixture obtained in (1), it was washed with water (10ml x 2 times), separated and dried over magnesium sulfate.

The organic layer was dissolved in 300 ml of carbon tetrachloride, and 4
136 g of bromine was added dropwise over 2 hours at 0 to 50°C, and the mixture was further stirred at the same temperature for 3 hours, but even at this stage, some polymerization occurred to form a rubbery substance. The resulting reaction mixture was concentrated under reduced pressure to remove the comb and give crude CH2BrCF.
BrCOC2H59Of was obtained. This was further distilled under reduced pressure to obtain a pure product 49.7f (0.179 mol). Yield 1
6.5%. Example 2 1) In a 100 m four-hole flask, CH2=CFCOF
lO. 9y (0.118 mol) of carbon tetrachloride 507n1
Add a small amount of dimethylformamide to the solution and
12.4y (0.176 mol) of gaseous chlorine was bubbled in at 0C.

The solvent was removed under reduced pressure to give the crude CH2ClCFCICOF.
23.5V was obtained.

0-MS: 115 (M+-COF), 49 (C) L. C
l), 47 (COF).

2) Next, excess methanol was added to the product obtained in (1) in 30 to 4 (generations) for esterification.

The reaction mixture was washed with water, separated and dried over magnesium acid to give 32 l. of crude CH2ClCFClCOOCH. 3f(0
．． 076 mol) was obtained. This is simply distilled to produce a pure product of 13.4
I got y. Yield 64.7%. 0-MSll5 (CH2ClCFCl), 59 (COOCH3), 15
(CH3).

Example 3 (1) CH2=CFCOCl9.8y (a).
A small amount of methylaniline was added to 50 ml of a solution of carbon tetrachloride (0903 mol), and 7.1 y of gaseous chlorine was added at 30 to 40°C.
was blown in while stirring.

Distill the solvent to give CH2ClCFClCOCl4.9y
I got it.

0-MS: 115 (CH2CICFCl), 66 (CF
Cl), 8 (COC).

2) Next, excess ethanol was added to the product obtained in (1) at 40-50'C for esterification.

The reaction mixture was washed with water, separated and dried over magnesium sulfate to give 9.7 g of crude CH2CICFCICOOC2H5l.
I got it. This was simply distilled to give a pure product of 14.0y (0.074
mole) was obtained. Yield 82.0%. 0-MS: 153 (M
+1 CI), 115 (CH2ClCFCl), 49 (C
H2Cl), 29(C2H5).

Claims (1)

[Claims] 1. An acrylic acid halide represented by the general formula: CH_2=CFCOX (wherein, X represents a halogen) has the general formula: ) represents a different halogen to obtain a compound represented by the general formula: CH_2X′CFX″COX (wherein, X, X′ and X″ have the same meanings as above), and then Then, this compound is reacted with water, alcohol or ammonia to form a compound of the general formula: CH_2X'CFX"COY (wherein, X' and X" have the same meanings as above. Y represents a hydroxy group, an alkoxy group or an amino group. ) A method for producing a halogenated propionic acid derivative, which is characterized by obtaining a compound represented by: 2. The manufacturing method according to claim 1, wherein X' and X'' are both bromine. 3. The manufacturing method according to claim 1, wherein X is fluorine and Y is an alkoxy group.