JPS60181040A - Preparation of fluorine-containing alcohol - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as a building block for introducing a fluorine-containing group, a solvent, etc. in high yield, by reacting a carbonyl compound with a fluorine-containing allylsilane compound. CONSTITUTION:A carbonyl compound shown by the formula I (R<1> and R<2> are H, aliphatic or aromatic hydrocarbon group, or heterocyclic group which may contain substituent group) is reacted with a compound such as beta-trifluoromethylallylsilane, shown by the formula II (Rf is fluorine-containing aliphatic group; R<3> is aliphatic or aromatic hydrocarbon group) in the presence of an alkali metal fluoride, preferably cesium fluoride, to give the desired compound shown by the formula III. An amount (concentration) of the alkali metal fluoride used is 5- 30mol%, preferably 20-25mol%.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a fluorine-containing alcohol.

In recent years, fluorine-containing compounds have attracted much attention in various fields such as medicines, agricultural chemicals, and various surface treatment agents. However, one important problem is how to selectively introduce fluorine into the desired position within the molecule, but until now such selective introduction of fluorine has not been possible easily and with high yield. Very little is known about how to do this.

The object of the present invention is to solve the above problems and improve the CF.

The object of the present invention is to provide a method that allows the fluorine-containing group to be present at a desired position and to incorporate the fluorine-containing group into the molecule of another compound.

That is, the present invention represents a group represented by the general formula: selected from the group consisting of a hydrogen atom, an aliphatic or aromatic hydrocarbon group which may have a substituent, and a heterocyclic group. ) and the general formula: (wherein, Rf is a fluorine-containing aliphatic group, and Rg is an aliphatic or aromatic hydrocarbon group), and the general formula: %formula% (however, R1 , R2 and Rf are the same as those described above.

In the method according to the present invention, in the general formula of the carbonylated metal product, R1 or R1 is an alkyl group such as a methyl group, an ethyl group, a propyl group, an isobutyl group, a butyl group, an isobutyl group, or a partially unsaturated Although an alkenyl group having a bond can be used, it is preferable that the number of carbon atoms is 10 or less. In addition to these, aromatic heterocyclic groups such as an aryl group, a furan ring group, a thiophene ring group, a pyrrole ring group, and a bilane ring group can also be used as R1 or R2.

Furthermore, in the general formula of the fluorine-containing allylsilane compound, R
4 (fluorine-containing aliphatic group) has the general formula: CFs (C
Examples include fluorine-containing aliphatic groups represented by Fs)n- or (CF, ), CF(CF,)n-.

This includes CF, -1CF, CF2-1CF s (C
F x ) x-1CF*(CFs)s-1cF, (
cF', ) 4-1CFs(CFt)s-1(CF3
), CF-1(CFs) x CFCF! -1
(CFs)zC”(CF,”)t-1(CF,),CF
(CFs)s-, etc.

In addition to these alkyl groups, unsaturated groups, especially alkenyl groups, such as CF, =CF-CF, -1CF, -CF=C
F- etc. are also applicable. However, the number of carbon atoms of the applied fluorine-containing aliphatic group is preferably 10 or less in consideration of solubility in a solvent.

In addition, the above-mentioned fluorine-containing aliphatic group is not limited to the perfluoroalkyl group or alkenyl group listed above, but also includes a hydrogen atom bonded to a part of the molecular chain, such as CFs (CFz).
zcH*cFz- is also applicable.

Furthermore, in addition to the above, Rf may include aromatic group-substituted fluorine-containing alkyl groups, such as C, H, -CF, -5CsHi
(CF,)! - etc. may also be used. Further, R3 includes the same alkyl group or alkenyl group as R1 or R2 above, and furthermore, an aryl group and an aralkyl group (the substituent in this case may be the alkyl group described above).

Furthermore, the alkali metal fluoride used in the reaction effectively acts as a fluoride ion source, and is indispensable for obtaining the desired fluorine-containing alcohol. In particular, cesium fluoride gives good results, and the amount (concentration) used is 5 to 30.
It is preferable to set it as mol% (preferably 20-25 mol%).

The above-mentioned fluorine-containing allylsilane compound has the general formula: % formula % (However, R3 is the above-mentioned aliphatic or aromatic hydrocarbon group, M is an element of Group Ma of the periodic table such as an alkaline earth metal atom, or periodic Metal halide of silane represented by the following formula: % formula % (where Rf is a fluorine-containing aliphatic group and R4 is an aliphatic group). or aromatic hydrocarbon group) is reacted with a fluorine-containing carboxylic acid ester represented by the general formula: % formula %) (however, R3 and R are the same as above). One molecule of (R”)ssiOH (where R
3 is the same as described above. ) can be synthesized by eliminating.

Here, as the metal halide of the above-mentioned silane, Rs is the same as above, and M is an element of group Ha of the periodic table such as an alkaline earth metal atom such as magnesium, or a group M of the periodic table such as cerium, yttrium, ytterbium, etc. Elements such as manganese and other elements of group 1b of the periodic table are applicable. Also,
Examples of the halogen atoms include chlorine atoms and bromine atoms. The above fluorine-containing carboxylic acid ester (R[C0OR
In '), the same various fluorine-containing aliphatic groups as mentioned above can be applied to Rf, and the same aliphatic group or aromatic hydrocarbon group as the above-mentioned Rs can be applied as R4.

In addition, in order to eliminate the above-mentioned (R"), 5iOH, if an acid or alkali is applied to the fluorine-containing carbinol f ((R"), 5iCH, CCH, 5i(R"),) Good. Usable acids include sulfuric acid, phosphoric acid, and trifluoroacetic acid, and usable alkali is KH.

Next, the present invention will be explained based on a specific example of the following formula applied to the introduction of CF and groups into alcohols.

First, ethyl trifluoroacetate, which is available at low cost as a source of CF, is reacted with Grignard reagent 1 obtained from chloromethyltrimethylshicine and magnesium.
After adding carbinol, peadarin (peters)
on ) elimination of β-trifluoromethylallylsilane in a good yield (e.g. 60%).
) can be obtained. This reaction can be expressed by the following formula (however, the (CHs)sSi- group is abbreviated as TMS).

2(TMS) CH, MgCj+CF, CO, C, H.

Yu C.F.

1 However, in this reaction, when removing TMSOH,
Water cooling (e.g. 50-60℃), reduced pressure (e.g. 20mmH)
g) It is preferable to apply concentrated H, 804 under the following conditions.
If the temperature is not raised or the process is not carried out under reduced pressure, -
The TMS group that should remain in 1 may also be removed. The fluorine-containing allylsilane 1 obtained in the above reaction has a boiling point of 106.5
~107.0°C, and is very stable at room temperature and pressure, and can withstand long-term storage.
Purification can also be easily carried out by distillation.

Next, using the above allylsilane 1, a reaction with a carbonyl compound (R'-C-R"), which is a claimed electronic reagent, is attempted. 0 First, as is generally known, a Lewis acid (for example, Ti (JiiBF, ・o(czHs)z, ZHBrz)
We investigated a method of reacting non-fluoroallylsilane and aldehyde in a methylene chloride solvent using No product (adduct i) is obtained.

C.F.

lewis acid 1111 → (product not obtained) CH, CI.

Therefore, the present inventor used cesium fluoride (C,F) at a predetermined concentration in the reaction of fluoroallylsilane and carbonyl compound-1 such as aldehyde, and as shown in the following formula, the desired purpose was achieved in high yield. It was found that the additional weight can be obtained.

C.F.

1 0HCF.

This reaction proceeds at room temperature and pressure for about one to several hours.
In addition, good results are obtained when dimethylformamide is used as the solvent. In addition to this, dimethyl sulfoxide, tetrahydrofuran, dimethylacetamide, N
-Methylpyrrolidone, hexamethylphosphoamide, etc. can be used.

Such polar solvents have a strong dissolving effect because they have a large solvation energy for cations, and have the effect of increasing the reaction rate of anionic reagents.

Both of the above reactions can be well explained by considering the following reaction mechanism.

R”CHO+ALn (Lewis acid) Soichi→(R' CH= 0+:Lng R' C”H-
0 Niri,) Engineering CF.

F 3 to 0 (TMS) CFs C 1 reciprocal In both of these reactions, intermediates 11 and 11 are thought to be produced, respectively, but the difference in stability of these intermediates makes it possible for the reaction to be successful when a Lewis acid is used. This is considered to be the reason why the reaction does not proceed, but when C and F are used according to the present invention, the reaction proceeds and the desired product 1 is obtained in good yield. That is, at an intermediate weight, CF and the group are mutually destabilized due to their strong electron-withdrawing properties, but the intermediate 7 is stabilized.

In the above reaction according to the present invention, the fluoride ion (Fo) generated in the intermediate stage directly serves as a fluorine source together with the alkali metal fluoride, so that the carbanion 1 can be easily and sufficiently produced. To obtain the target Σ, acidic conditions (e.g. methanol-INHCJ) are required.
However, if it is not acidified, silyl ether corrosion remains with the trimethylsilyl group (TMS) remaining intact.

In the above reaction, the target product can be obtained in good yield by using cesium fluoride as a fluoride ion source. It has also been found that when hexamethylphosphoryltriamide, etc., which are known to promote ionic reactions, is added, the yield of Target Product 1 is not affected.

The present inventor conducted various reactions using CSF, and was able to obtain good results as shown in the table below.

This demonstrates the usefulness of the allylsilane compound l mentioned above, and also demonstrates the usefulness of the above-mentioned allylsilane compound l, as well as fluorinated alcohols made of various 2-trifluoromethyl-4-hydroxy-1-butenes with a trifluoromethyl group introduced at the target position (β-position). This means that it is a useful method that can efficiently obtain data.

(Continued on next page) *Isolated as alcohol **Isolated as silyl ether, ribs, etc. From the above results, in order to improve the yield of the target product, R1 of the carbonyl compound should be compared. It turns out that it is better to apply an alkyl group that is not a long chain.

The fluorine-containing alcoholic acid obtained above is useful as a solvent, physiologically active substances such as herbicides and insecticides, or intermediates for building blocks thereof.

Next, specific examples of the present invention will be described. However, the following examples do not limit the present invention, and various modifications can be made based on the technical idea thereof.

111 (1), 2 (TMS) CH, MgC1+CF3CO,
C,H.

Mg (9,72g
.

Add 0.4 mol) and ether (aoomJ), and add (
CH,)sSiCH,CI! (49.1g, 0.4mo
By slowly dropping l), (CH,)18
i CH2MgCl was synthesized. CF3CO to this Grignard solution.

C! After adding H, (28.4 g, 9.2 mol) dropwise over 1 hour, the mixture was stirred at room temperature for 1 hour. After reaction, I
The reaction was stopped with NHCJ solution, and the resulting oil layer was separated. After distilling off the solvent, the product (39
, ag) was obtained with a yield of 73%. The boiling point of this product (
bp) ss, o ~86.0°C/14 mm Hg.

Moreover, the analytical data of this product were as follows.

"F NMR (external standard CF3CO, H): 4.0 (
CF,) "HNMR (C'DCJ,: the same applies hereafter): τ9.96 ~
9.8K S i (CHs ) □), 9.03-8.
81 (CH, (10
oml) in 3 tube flasks (2o.

Set the distillation device and dropping funnel on the JL (
27.2 g, 100 mol) was slowly added dropwise using a water bath, and the produced allylsila 4 was trapped under reduced pressure. The product was redistilled to obtain allylsilane (14,
4g) was obtained with a yield of 79% and a bp of 106.5-107-0°C.

The analytical data for this product were as follows.

"F NMR: -8,4 (CF Riki NMR: τ9.93 (S i (CHs) x
), 8.39 (CH,), IR: 1650C1l (C=C) Example 1 0HCF.

1 PhcHcH, -C=CH! Synthesis: Benzaldehyde (0,
24 g, 2.3 mmol), dimethylformamide (5 mj), and C5F (77.2 mg - 0.51 mmol) were added, and β-trifluoromethylallylsilane (
0.36 g, 2.0 mmol 1 ) was added dropwise. After reacting for 2 hours at room temperature, water was added and the oil was extracted with ether. After the solvent was distilled off, the residue was purified by column chromatography (using hexane-ether (3:1) as a solvent). The yield was 99%.

The analytical data for this product were as follows.

1″’F NMR knee 10.2 (CF,) 2.75 (
Ar-H) I R: 3400 Cal-" (OH) Example 2 Synthesis of C, H, 3CHCH, C=CH,: 10HCF.

Heptanal (0,2
4g2, 1 mmol) and dimethylformamide (5mj)C,F (68.7mg, 0.45mmol)
and β-trifluoromethylallylsilane (
0.36g.

2.0 mmol) was added dropwise. After reacting for 2 hours at room temperature, water was added and the resulting oil was extracted with ether. After evaporating the solvent, the residue was purified by column chromatography (using hexane-ether (6:1) as a solvent). The yield was 61%.

The analytical data for this product were as follows.

1”F NMR: -10,0(CF3)”HNMR(
CD (J3): τ9. 'l I CCHs), I R
: 3425 Ca1-” (0H) 3 flask (
10mg), citronellal (0.32g, 2.
1 mmol), and dimethylformamide (5 mmol
g), C,F (63.9 mg, 0.42 mmol) and β-trifluoromethylallylsilane (0,
36 g, 2.0 mmol 1 ) was added dropwise. After reacting for 5 hours at room temperature, water was added and the resulting oil was extracted with ether. After distilling off the solvent, the residue was purified by column chromatography (using hexane-ether (8:1) as a solvent). The yield was 83%.

The analytical data for this product were as follows.

"F NMR: -9,95 (CF,)" HNMR (C
'Dcz,):r9. o6~9.09 (CH,), 8.
35-8.41 (CH, X2'), 7.82-8.95
(CH,X3°OH), 6.19 (CHOH), 4.
97(-/), IR: 3375C11-”(OH
) Example 4 0 (TMS) CHmCFm.

Synthesis: 3 turophrass: + (25 mj), acetophenone (0
, 26g.

2.2 mmo 1 ) and dimethylformamide (5
mj), C', F (80.2 mg, 0.53 mmol)
β-trifluoromethylallylsilane (0.36g,
2.0 mmol) was added dropwise. After reacting for 5 hours at room temperature, water was added and the oil was extracted with ether. After the solvent was distilled off, the residue was purified by column chromatography (using hexane-ether (3:1) as a solvent).

The yield was 81%. (However, isolated yield as silyl ether).

The analytical data for this product were as follows.

19F NMR: -10,4(CF3)2.49~2
．． 85 (Ar-H), 9.97 (Si(CHl), )I
R: 2950C1l-” (CH3) Agent: Patent attorney Hiroshi Suita (1 other person)

Claims (1)

[Claims] 1. General formula: (However, R1 and R2 are the same or different groups, and include a hydrogen atom, an aliphatic or aromatic hydrocarbon group which may have a substituent, and a hetero (represents a group selected from the group consisting of cyclic groups), and a carbonyl compound represented by the general formula: A method for producing a fluorine-containing alcohol, which is characterized by reacting and obtaining a fluorine-containing alcohol represented by the general formula: % formula % (wherein R1, R2 and Rf are the same as those described above).2 , R1 or R2 is an alkyl group having 10 or less carbon atoms,
The method according to claim 1, wherein the alkenyl group, aryl group, or aromatic oxygen-containing, sulfur-containing, or nitrogen-containing heterocyclic group has 10 or less carbon atoms. 3. R (represents a fluorine-containing alkyl group having 10 or less carbon atoms or a fluorine-containing alkenyl group having 10 or less carbon atoms,
A method according to claim 1. 4. The method according to claim 1, wherein R3 is an alkyl group having 10 or less carbon atoms, an alkenyl group having 10 or less carbon atoms, an aryl group, or an aralkyl group. 5. The method according to claim 1, wherein the reaction is carried out at a concentration of alkali metal fluoride of 5 to 30 mol%.