JPS62129242A - Production of fluorine-containing alpha,beta-unsaturated carboxylic acid - Google Patents

Abstract

PURPOSE:To readily obtain the titled compound in high yield under mild condition, by adjusting the concentration of CO2 in an organic solvent to a specific value, reacting a fluorine-containing halogenoalkene as a raw material in the presence of zinc and hydrolyzing the reaction product with a mineral acid. CONSTITUTION:A fluorine-containing halogenoalkene expressed by formula I (R1-R3 are H, F, alkyl or fluorine-containing alkyl and at least one therereof is F or fluorine-containing alkyl; X is Cl, Br or I), e.g. 3,3,3-trifluoro-2- iodopropene, etc., is reacted in the presence of zinc at 0-150 deg.C by adjusting the concentration of CO2 in an organic solvent to >=0.3mol/l and the reaction product is then hydrolyzed with a mineral acid to afford the aimed compound expressed by formula II, e.g. alpha-trifluoro-methylacrylic acid, etc. EFFECT:The purification process of the aimed compound is simplified and isolating operation is facilitated without requiring recovering operation of the unreacted raw material. USE:A synthetic intermediate for medicines and agricultural chemicals, raw material for polymers, e.g. resists for producing LSI, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing a fluorine-containing α,β-unsaturated carboxylic acid. For more details, see simple and efficient fluorine-containing α using fluorine-containing halogenated alkenes as raw materials.
, β-unsaturated Cal? The present invention provides a method for producing phosphoric acid.

Fluorine-containing α,β-unsaturated carboxylic acids are useful substances as intermediate raw materials for various fluorine-containing compounds, such as synthetic intermediates for pharmaceuticals and agricultural chemicals, materials for coatings, and raw materials for polymers used in LSI manufacturing methods. important as such.

[Conventional technology]

Conventional methods for producing fluorine-containing α,β-unsaturated carboxylic acids using fluorine-containing halogenated alkenes as starting materials include: ■ producing fluorine-containing vinyllithium or magnesium bromide from fluorine-containing vinyl bromide and n-butyllithium or magnesium; method of preparing and reacting with carbon dioxide at low temperature (e.g. Journal Op. Nick Kmistry (J, Org, Chem,) 33,280
(1967) or Chemical Abstracts (Che
m, Aba, ) 53.

6987g etc.).

■ Fluorine-containing vinyl halo r< compound and carbon dioxide are irradiated with ultrasonic waves in the presence of a zinc-copper pair (e.g., Japanese Patent Publication No. 6332/1983) or in the presence of zinc powder (e.g., 10th Fluorine Chemistry Discussion) Proceedings, 1985, p. 33, etc.) ■ In the presence of triethylamine and a palladium catalyst,
2-promo 3.3. A method of reacting 3-trifluoropropene, carbon monoxide, and water to synthesize α-trifluoromethylacrylic acid (for example, JP-A-58-154529
Publications, etc.).

etc. are known.

However, these conventional methods cannot be said to be fully satisfactory as engineering techniques. That is, in the method using n-butyllithium or magnesium, the reaction must be carried out at a low temperature of -100°C or -40°C, respectively, and the yield of the desired product is also low.

In the method using a zinc-copper pair, it is necessary to prepare the zinc-copper pair in the pre-reaction step, which complicates the reaction operation.Although relatively high yields may be obtained, a certain level of activity is required. There are problems such as difficulty in obtaining a zinc-copper pair having a high degree of strength and lack of reproducibility in yield. Furthermore, the method of irradiating ultrasonic waves in the presence of zinc powder cannot be said to be an efficient method from an industrial perspective because it is difficult to use a large-sized ultrasonic generator and the yield is low. The method using a palladium catalyst requires high pressure carbon monoxide (30 to 40 atm) and the reaction time is extremely long, so this method is also difficult to employ as an industrial synthesis method.

That is, the conventional method for producing fluorine-containing α,β-unsaturated carboxylic acid using a fluorine-containing halogenated alkene as a starting material requires (1) harsh reaction conditions, (2) low yield, and (3) reaction procedures. However, there were problems such as complexity.

[Problem that the invention seeks to solve]

In view of the above-mentioned circumstances, the present inventors conducted extensive research on a method that can easily produce fluorine-containing α,β-unsaturated caldicic acid in high yield under mild reaction conditions. This is what led to the present invention.

[Means for solving problems]

That is, the present inventor discovered that in a method of reacting a fluorine-containing halogenated alkene with carbon dioxide in the presence of zinc, the carbon dioxide concentration in the reaction system has a larger than expected effect on the yield of the target product. This led to the completion of the invention.

The inventor of the present invention discovered the above feature based on the following.

That is, in the reaction of a perfluoroalkyl halogonide with carbon dioxide in the presence of zinc, the general K, if
It is believed that the zinc and perfluoroalkyl halo f7ide form a reactive intermediate that reacts with carbon dioxide gas to form the zinc salt of the perfluoro-carboxylic acid. If this reactive intermediate is unstable in the reaction system, it will compete with side reactions such as decomposition reactions, resulting in a decrease in the selectivity of the target Cal-7 acid. Therefore, although it is not possible to increase the conversion rate of the raw material by increasing the concentration of carbon dioxide, which is one of the reactants, it is considered that the selectivity to the target carboxylic acid can be increased.

For this reason, a detailed study of the relationship between the carbon dioxide concentration in the reaction solvent and the yield revealed that the yield of perfluorocardic acid sharply increased when the carbon dioxide concentration exceeded a certain value. discovered the phenomenon of In other words, if the concentration of carbon dioxide is set to 0.3 mo/II or more, the target perfluorocar? It has become clear that phosphoric acid can be obtained with high selectivity and yield, and that the conversion rate can also be increased. Regarding the cause of this effect of carbon dioxide concentration,
Although it is not clear, in addition to the kinetic effect of increasing the concentration of the reaction reagents involved in one of the competitive reactions, it also causes changes in the physical properties of the entire reaction system, such as polarity and basicity. This is presumed to be because the stability of the reactive intermediate increased as a result, which also had the effect of increasing its production rate.

Based on this knowledge, when the above method was applied to fluorine-containing halogenated alkenes, exactly the same effect was obtained, and if the concentration of carbon dioxide in the organic solvent was set to 0.3 mol/l or more, The present invention was completed based on the discovery that fluorine-containing α,β-unsaturated caldicic acid can be obtained in high yield.

That is, the characteristics of the present invention are as follows: General formula; R, (R2)C=C(R,)X ・
...(I) (However, in the formula, R1, R2, R are hydrogen atoms,
A fluorine atom, an alkyl group, or a fluorine-containing alkyl group, at least one of which is a fluorine atom or a fluorine-containing alkyl group, and X represents any one of a chlorine atom, a bromine atom, and an iodine atom. ) A fluorine-containing halogenated alkene represented by g is reacted with carbon dioxide in the presence of zinc in an organic solvent, and then the reaction product is hydrolyzed to obtain the general formula; R1 (R2) C=C (R3) CO□H...(
II) (However, in the formula, R1, R2, and R are any one of a hydrogen atom, a fluorine atom, an alkyl group, and a fluorine-containing alkyl group, and at least one of them) represents an elementary atom or a fluorine-containing alkyl group. . ) is a fluorine-containing α,β-unsaturated cal? In the method for producing carbonic acid, the reaction is carried out at a concentration of carbon dioxide in an organic solvent of 0.3 mol/l or more.

The present invention will be explained in detail below.

As the fluorine-containing alkene represented by the general formula (I) used in the method of the present invention, various types can be used, but due to the reactivity of the alkene and zinc, the general formula (I) R1, R2
, R5 must be a fluorine atom or a fluorine-containing alkyl group.

Examples of such compounds include F2O-C(F)
X.

F2O-C(H)X, H(F)C-C(F)X 1
A fluorine-containing pinirno-rhodan compound represented by H(F)C-C(H)X, H2C-C(nX (in the formula, X represents either chlorine, bromine, or iodine atom), or a group of this compound. Hydrogen atoms or fluorine atoms are substituted with alkyl groups or fluorine-containing alkyl groups, for example, p2c
mc(u)x, F(R)C-C(F)X, H(R)
C-C(F)X, F(R)CC(H)X.

H(F)CC(R)X, p2cmc(ur)x
, r(Rf)cc(r)x.

a(Rf)cc(p)x XF(Rf)cc(n)
x, u(7)cc(Rf)x.

a2cmc(Rf)x, H2C-C(F)x,
nf2cmc(p)x.

Rr(R)cc(p)x, Rf2cmc(u)x
, Rr(R)c-c(u)x (wherein, R is an alkyl group, Rf is a fluorine-containing alkyl group, and X is a chlorine, bromine, or iodine atom). - or 2-no-rhodanated alkenes, and further,
F(R)CC(R)XXRf(F)CC(Rf)X
.

Rf2cmc(Rr)x, Rr(R)cc(a)x
XR2cmc(Rf)x.

Rf2cmc(R)xXRf(R)cc(Rf)x,
R(p)cc(Rf)x.

Rf(r)cc(R)x, Rf(a)cc(R
r)xXRr(a)c-c(a)x.

R(H)C-C(Rf)X (wherein, R is an alkyl group,
Rf is a fluorine-containing alkyl group, and X is a chlorine, bromine, or iodine atom. ), polysubstituted forms of R and Rf, etc. can be used. However, in consideration of the solubility of the fluorine-containing rhodanated alkene in a solvent, the number of carbon atoms in the alkyl group or fluorine-containing alkyl group is preferably 20 or less. Further, any fluorine-containing alkyl group can be used as long as it has a substituent effect similar to that of a trifluoromethyl group, but a perfluoro- or polyfluoroaliphatic group having a straight or branched chain is particularly preferred.

In the present invention, during the reaction, the concentration of carbon dioxide in the organic solvent must be 0.3 mol/l or more. If the carbon dioxide concentration is less than 0.3 mol/l, the high yield targeted by the present invention cannot be achieved.

Incidentally, the upper limit of the carbon dioxide concentration is actually sufficient at 5 mol/l. If it exceeds 5 mol/l, the effect of further improving the yield will be significantly reduced.

Usually, the carbon dioxide concentration in an organic solvent changes depending on the type of solvent and temperature. Therefore, the above concentration can be obtained by changing the selection of solvent or reaction temperature. However, more easily pressurized reactors (such as autoclaves)
By increasing the carbon dioxide pressure above normal pressure using , a predetermined concentration can be obtained regardless of the solvent and reaction temperature. For example, dimethyl sulfoxide (DMSO
), the carbon dioxide concentration is 0.1 at 0°C under normal pressure.
3 mol/l, but by adjusting the carbon dioxide pressure to 5 kg/m" (absolute pressure) using a pressurizing device, it can be reduced to 0.6
mol/l (35°C). In addition, dimethylformamide (hereinafter referred to as DMF) has a temperature of 20% under normal pressure.
The carbon dioxide concentration at °C is 0.23 mol/l, but if a pressurizing device is used, the concentration is 5ki7/ctn2 (absolute pressure),
It can be set to 0.85 mol/l at 35°C.

In the above reaction method, the zinc used can be used in the form of powder, the average particle size of which is 0.1 μm to 1 μm.
It is preferable that the thickness is in the range of 00 μm.

If the particle size is 0.11 μm or less, the operation for removing it after the reaction becomes complicated, and if it is 100 μm or more, the reaction yield decreases, probably because the effective area used during the reaction decreases. From the viewpoint of reaction yield and operation, the average particle size is 1 μm to 50 μm.
It is particularly preferable that

Commercially available zinc powder can be used satisfactorily without treatment, but the amount used can be reduced by surface-treating the zinc in advance. The surface treatment method is Horben-WeyA + 13 (2a
).

(pp. 570-574 and p. 815), for example, by pre-treatment with an acid treatment agent (such as mineral acid or acetic acid), or by treating with other metals (such as generally copper, lead, cadmium, to form a metal pair with mercury, etc.)
It can be processed.

Zinc powder has a ratio of 1 to 1 for fluorine-containing halogenated alkene.
It may be used in an amount of 5 equivalents, but it is preferable to use 2 to 5 equivalents in order to perform the reaction with good reproducibility.

As the solvent used in the method of the present invention, aprotic polar solvents are preferred, and examples of these solvents include DM
F, DMSO, N,N-trimethylacetamide, tetramethylurea, hexamethylphosphoramide, sulfolane, N-methylpyrrolidone.

Nitrobenzene, nitromethane, acetonitrile.

carbonic acid, propylene, tetrahydrofuran, dioxane,
These include ether, diglyme, triglyme, and pyridine. From the viewpoint of reaction yield, DMF, DMSO
, N-methylpyrrolidone, N,N-tmethylacetamide, tetramethylurea, and hexamethylphosphoramide are preferred, and DMF is more preferred.

The reaction of the present invention can be carried out over a wide temperature range, but typically
It is desirable to carry out at a temperature range of 0 to 150°C. At temperatures below 0°C, although the carbon dioxide concentration in the solvent is high, RfX
The reaction time required to increase the conversion rate is extremely long, which is not practical. Furthermore, at temperatures as high as 150°C, high pressure is required to maintain the carbon dioxide concentration in the solvent at a predetermined value.
Cal because the rate of side reactions increases? The selectivity to phosphoric acid decreases significantly.

The reaction can be carried out by contacting the above-mentioned fluorine-containing halogenated alkene with carbon dioxide at a predetermined temperature in an organic solvent with zinc suspended therein. Since the concentration of carbon dioxide in the reactor is important, the concentration of carbon dioxide must always be maintained at 0.3 mol/l or higher from the start to the end of the reaction. To do this, the carbon dioxide concentration must be set high at the start of the reaction so that the concentration is maintained at 0.3 mol/l or more at the end of the reaction even if the carbon dioxide is consumed during the reaction, or Either method may be used in which carbon dioxide equivalent to the amount consumed during this period is constantly supplied to the solvent. The fluorine-containing halogenated alkene is desirably added to the system after setting a predetermined concentration and carbon dioxide concentration in the presence of zinc and a reaction solvent.

The slower the addition rate, the better from the viewpoint of yield of the target product.
Solvent 1j A9F) 0.05 mo 1/hr ~10
It is desirable that it be in the range of mol/'hr. Q, 0
If it is less than 5 mol/hr, the addition time is too long to be practical. Moreover, if it exceeds 10 mol/hr, the yield of the target product will drop significantly. When carrying out this addition method, a reaction time of 30 minutes to 10 hours after the addition of the fluorine-containing halogenated alkene is completed is sufficient. However, if the fluorine-containing halogenated alkene is a solid and has low solubility in the reaction solvent, the above addition method cannot be used,
The reaction can also be carried out by adding a solvent to a system in which zinc and the halide are mixed in advance in a carbon dioxide atmosphere. When this addition method is used, a sufficient reaction time is 30 minutes to 10 hours after the addition of the solvent is completed and the temperature is set at a predetermined temperature.

After reacting the fluorine-containing halogenated alkene with carbon dioxide in the presence of zinc as described above, the reaction product is hydrolyzed to obtain the desired fluorine-containing α,β-unsaturated alkene. You can obtain phosphoric acid. Hydrolysis easily proceeds by bringing the reaction mixture into contact with a mineral acid such as hydrochloric acid, sulfuric acid, or nitric acid.

〔Effect of the invention〕

According to the method of the present invention, a fluorine-containing halogenated alkene can be almost uniformly converted into the desired fluorine-containing α,β-unsaturated caldic acid without producing any by-products. . Furthermore, as a result, there is no need for an operation for recovering unreacted raw materials, and furthermore, the process for producing the target product is simplified, and the isolation operation is facilitated.

〔Example〕

The present invention will be explained in more detail with reference to Examples and Comparative Examples below, but the present invention is not limited thereto.

Examples include carbon oxide inlet and 31313-) +) fluoro-
19.6 g of zinc powder (average particle size: approximately 15 μm), which had been previously washed and dried with a 0.5 N hydrochloric acid aqueous solution, was added to a 200 CC electromagnetic stirring autoclave equipped with an injection port for 2-iodopropene, and heated externally. The temperature inside the autoclave was set at 35°C. 6. Carbon dioxide pressure via constant pressure device.
After setting the pressure to 0 kg/cm2 (absolute pressure), the carbon dioxide pressure inside the autoclave was maintained at this pressure until the end of the reaction. Next, 80M DMF was added into the autoclave while stirring using a one-liquid pump. When DMF is injected into the autoclave, it begins to dissolve carbon dioxide, and the final concentration reaches a gas phase carbon dioxide pressure of 6. o kg/α2
(absolute pressure) is the saturated solubility concentration (1 mol/l). Then 3 of 22.2.9 (0.10 mol)
．． 3.3-Trifluoro-2-iodopropene and 10
A mixture of TL1 and DMF was pressurized into the sciautocrape using a liquid feed pump over a period of 1 hour. After stirring for another 2 hours at the same temperature, the pressure of carbon dioxide in the autoclave was returned to normal pressure to terminate the reaction.

After removing 13 g of excess zinc from the reaction mixture by filtration, a portion of the solvent DMF' was recovered by distillation, and the filtrate was concentrated. The concentrated solution was then poured into a 6N aqueous hydrochloric acid solution to hydrolyze the reaction intermediate. It was then extracted with diethyl ether and the extract was dried. The ether was distilled off to obtain 11.5I of α-trifluoro-methylacrylic acid (yield: 82I). The product is a G
L.C., I.R.

Examples 2 to 4 identified by comparison of spectral data such as NMR Carbon dioxide pressure and reaction temperature were set as shown in Table 1,
Everything was carried out in the same manner as in Example 1, except that the carbon dioxide concentration in DMF' was changed. These results are shown in Table 1.

Table 1 Examples 5 to 7 All except using the solvent shown in 2.2 instead of DMF.
Table 2 shows the results obtained in the same manner as in Example 1.

Table 2 Example 8 3.3.3- ) Refluoro-2-bromozolopair (CF3BrC-CH2) 1F59 (0
, 10net) was carried out in the same manner as in Example 1 to obtain 8.4 g (yield: 60%) of α-trifluoromethylacrylic acid.

Example 9 23.0 g of commercially available zinc (average particle size 15 μm)
As a result of carrying out the same operation as in Example 1 except that α-trifluoromethylacrylic acid was used, α-trifluoromethylacrylic acid was obtained in a yield of 80q6.

Example 10 5011L1! In a mixed solution of DMF and 10-acetic acid,
0.6ji of acetic acid steel was added and heated to 40-50°C, and commercially available zinc powder of 19.6.9 was added thereto and stirred for 30 minutes. After cooling, it was washed four times with 25 mJ of DMF to obtain a zinc-copper pair. A reaction was carried out in the same manner as in Example 1 except that this zinc-copper pair was used in place of the zinc powder described in Example 1. As a result, α-trifluoromethylacrylic acid was % yield.

Examples 11-14 3.3+3-) 9.10 mol each of 3.3, 4.4, 5, 5 instead of y-fluoro-2-iodopropene
．． 6,6.6-nonafluoro-2-iodohexene, 1
, 2.2-) refluoro-1-iodoethene, 1.2
-difluoro-1-iodo-3-methylpentene or 2°3.3,4,4,5,5,6,6,7,7,8,
The procedure was carried out in the same manner as in Example 1 except that 8,9,9.9-hexadecafluoro-1-iodo-nonene was used to obtain a widely distributed α,β-unsaturated carboxylic acid. The product is IR,
It was identified by NMR etc. The results are shown in Table 3.

19. In a 300-40 flask equipped with a carbon oxide inlet tube, 9 funnels, a reflux condenser (dry ice-acetone), and a stirrer, the 19. Add 6 g of zinc powder (average particle size about 15 μm) and 80 mA' of DMF, and add 4 g of carbon dioxide under normal pressure.
Aerated at 5 ml/min for 30 minutes (temperature 25
0.2 mol/l of carbon dioxide in DMF')
. Then 1. While aerating carbon dioxide at the same flow rate, 22.2 g of 2~yaw)'-3,3,3 was added through the dropping funnel.
- A mixture of trifluorozolopene and 10% DMF' was added dropwise over a period of 1 hour.

After stirring for an additional 4 hours at the same temperature and removing excess zinc from the reaction mixture, 5
．． 6. ! i2 α-trifluoromethylacrylic acid (yield 40%) was obtained.

Comparative Example 2 Increase the pressure inside the autoclave to 6kVrrL2 with carbon dioxide
The process was carried out in the same manner as in Example 1, except that a mixed gas of carbon dioxide and nitrogen (carbon dioxide 15.7 vol. mol A. The yield of α-trifluoromethylacrylic acid was 42q6.

Claims (5)

[Claims] (1) General formula; R_1(R_2)C=C(R_3)X(
However, in the formula, R_1, R_2, and R_3 are any one of a hydrogen atom, a fluorine atom, an alkyl group, and a fluorine-containing alkyl group,
and at least one is a fluorine atom or a fluorine-containing alkyl group, and X is a chlorine atom, a bromine atom, or an iodine atom. ) is reacted with carbon dioxide in the presence of zinc in an organic solvent,
The reaction product is then hydrolyzed to give the general formula; R_1(R_
2) In the method of producing a fluorine-containing α,β-unsaturated carboxylic acid represented by C=C(R_3)CO_2H, the reaction is carried out at a concentration of carbon dioxide in the organic solvent of 0.3 mol/l or more. A method for producing a fluorine-containing α,β-unsaturated carboxylic acid characterized by (2) The method according to claim (1), wherein the fluorine-containing alkyl group is a linear or branched perfluoro or polyfluoroaliphatic group having 1 to 20 carbon atoms. (3) Claim (1) or (2) wherein the concentration of carbon dioxide in the organic solvent is in the range of 0.3 to 5 mol/l.
) method described in section (4) Preliminarily activated or untreated zinc is added to the fluorine-containing halogenated alkene to
Claims (1) to (3) using equivalent amounts
The method described in any of the sections (5) The method according to any one of claims (1) to (4), in which the reaction is carried out at a temperature range of 0 to 150°C.