JPS6212741A - Production of 2-perfluoroalkylacrylic acid - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an intermediate for carcinostatic agent in high yield at a low cost, by reacting 1-perfluoroalkyl-1- haloethylene with metallic magnesium, reacting the reaction product with carbon dioxide, and treating with an acid. CONSTITUTION:The objective compound of formula II useful as an intermediate for trifluorothymidine (a carcinostatic agent) is produced economically, by (1) reacting the compound of formula I (Rf is perfluoroalkyl; X is Cl, Br or I) with metallic magnesium at room temperature usually using tetrahydrofuran as a solvent, (2) reacting the reaction mixture with carbon dioxide preferably at +10--10 deg.C by introducing carbon dioxide gas into the reaction system, and (3) treating the resultant reaction mixture with a mineral acid, preferably hydrochloric acid, sulfuric acid, etc. The starting compound of formula I can be easily produced by halogenating a perfluoroalkyl-substituted ethylene derivative which is readily available on an industrial scale.

Description

DETAILED DESCRIPTION OF THE INVENTION [Object of the Invention] The present invention relates to the general formula (wherein ft and f are perfluoroalkyl groups).
〇 [Industrial Application Field] The 2-perfluoroalkyl acrylic acid represented by the general formula ω obtained by the present invention is prepared by:
By reacting with urea, 4<4> can be converted to 5-perfluoroalkyldihydrouracil. 5-Perfluoroalkyldihydrouracil can be induced to trifluorothymine by reacting with bromine in acetic acid and then heat-treating (C, Heidelberge
r* D-G-Parsons and D-C-fi
amy, J+Med, Chem.

7, 1 (1964): +, ) Trifluorothymidine, which is a condensation of lifluorothymine and sugar, and its derivatives are used as anticancer agents (Jpn, Kokai Tokkgo
Koho JP59e36.696 X 59,21
6,899).

[Conventional technology]

Conventionally, for example, a method for producing 2-perfluoroalkyl acrylic acid has been as follows:H)) Lifluoroacetone is converted into cyanohydrin, acetylated and then thermally decomposed to synthesize α-trifluoroacrylonitrile, which is then hydrolyzed.
A method for synthesizing α-trifluoroacrylic acid by adding hydrogen chloride and then performing hydrolysis and dehydration reactions [MW, Buxton* M, 8tacey,
and JC-TaNow+J, Chem So
c, , 367 (1954) - Reference], (b) 3
, 3. α-trifluoroacrylic ff by reaction of 3-trifluoroinopropenyl lithium with carbon dioxide
It-Method of Synthesizing (FG-Drakesmith.

0, J, 8tewart, and P, Tarr
ant J.Org.

Chemo. Method (Unexamined Japanese Patent Publication No. 1983-
154529) is known.

[Disadvantages of conventional method]

However, method (e) requires a long reaction step,
Moreover, the total yield was less than 10%, and the method (b) used flammable butyllithium and under anhydrous conditions, -110t
The disadvantage is that the reaction must be carried out at extremely low temperatures. In addition, the method () and () uses extremely expensive palladium as a catalyst, so there is a problem in its industrial application.

[Problems solved by the invention]

As a result of studies to overcome the conventional drawbacks, the present inventors have found that acrylic lI in 2-perfluoroalcohol can be used in a high yield and at low cost.
l! They discovered that gold can be produced and completed the present invention.

[Structure of the invention]

The present invention is based on the general formula (wherein) t and f are perfluoroalkyl groups, and
is a chlorine atom, a bromine atom or an iodine atom. ) After reacting the ethylene derivative represented by the above formula (
The compound represented by the general formula (II) can be easily obtained by halogenating an industrially easily available perfluoroalkyl-substituted ethylene derivative. It is a compound that can be manufactured. In the general formula (I[), f is a trifluoromethyl group, a pentafluoroethyl group, a perfluoroprobyl group, a perfluorobutyl group, a perfluoropentyl group, a perfluorohexyl group, a perfluoroheptyl group, a perfluorooctyl group, perfluorononyl group,
Examples include perfluorodecyl group, where X is chlorine
・The reaction with Neshiu 4 is usually exemplified by atoms, bromine atoms, and iodine atoms.
The reaction is carried out at room temperature using the solvent as a solvent. [In the present invention, the reaction product to be subsequently carried out is reacted with carbon dioxide t-1.
1 reaction involves blowing carbon dioxide into the reaction system.
1, and the reaction temperature is N
A range of OC to -10C is suitable.

In the present invention, t-2-perfluoroacrylic acid represented by the general formula (I) is produced by further treating the obtained reaction mixture with an acid.

As the acid that can be used for the acid treatment, mineral acids such as hydrochloric acid and sulfuric acid can be suitably used.

Hereinafter, the present invention will be explained in more detail with reference to Examples.Example 1 Magnesium for Grignard reaction (2.43g, 100rr
ono l) Place in a Mitsuro flask equipped with a T-gas inlet pipe and a discharge pipe, and add dry GK nitrogen gas to approximately 50m17f.
The mixture was stirred vigorously with a magnetic stirrer and a mechanical stirrer for one day while flowing with a
Dry tetrahydrofuran (20 ffij) was added, and the suspension was passed through an approximately 80-mesh Teflon sieve, the solvent was removed at normal pressure, and 1.2 gt of fine magnesium powder was obtained.
Obtained.

Magnesium fine powder (0.5 g, 20 mmol) was placed in a Mitsuro flask equipped with a dry ice-acetone reflux condenser.
, dry tetrahydrofuran (10 mg) was added thereto, and 2-proso-3,3°3-trifluoropropene (3.5 g, 20 mmol) was slowly added dropwise with vigorous stirring. After completion of self-reflux, stirring was continued for 1 hour.

The resulting reaction mixture, a tetrahydrofuric acid solution, was cooled in a water bath, and 2.51 (112 mmol) t of carbon dioxide gas was added.
-Yutsukushi filled in. After stirring for 1 hour, 1-T-hydrochloric acid was added, and extraction was performed with ether.

The solvent was distilled off from the ether layer under reduced pressure, and the oily residue t-g
Pressure distillation to obtain α-trifluoromethylacrylic*(2,5
g) was obtained.

b-P-85-86 G/35 mmHg, yield 89%
.

Example 2 2-n-perfluorobutyl acrylic! under the same conditions as in Example 1 except that l-n-perfluorobutyl-1-bromoethylene was used. Obtained with a yield of 74%.

m-p-82-84G IH-NMR (C1) CI, two TMS);
δ6.57 (m, 1) 1) 17.03 (d,
0.4H2+ IH) 12.45(s, 1)1)
・IkL CKBr d 1sk) cm-” ;304
0 ('0-H) + 1720 ('c=o), 1350 ('C-F)l 1170 ('C-F).

Claims (1)

[Claims] (1) After reacting the ethylene derivative represented by the general formula ▲numerical formula, chemical formula, table, etc.▼ with metallic magnesium, the reaction mixture is reacted with carbon dioxide, and then the reaction mixture is treated with an acid. Method for producing 2-perfluoroalkyl acrylic acid represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (wherein, Rf is a perfluoroalkyl group,
X is a chlorine atom, a bromine atom or an iodine atom. ).