JPS6055046B2 - Method for producing fluorine-containing carbinol - Google Patents

Description

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

Fluorine-containing compounds have many useful uses due to their excellent stability, chemical resistance, weather resistance, water and oil repellency, physiological activity, and the like.

Various studies have been conducted on compounds having a fluoroalkyl group in the molecule, and several new synthetic methods have been developed. The reported synthesis methods include:
For example, for a compound containing a trifluoromethyl group, (1
) Direct fluorination of methyl groups with metal fluorides, (
2) halogen exchange reaction of CCl3 groups with HF-SbCl, (3) method of fluorinating COOH groups with SF4,
(4) Radical reaction to introduce CF3 group into a heterocyclic compound, (5) Iodine introduced into an aromatic compound into R, CUI
(R, is a fluorine-containing aliphatic group; the same applies hereinafter) to replace Rf. (Ullmann reaction). Additionally, trifluoromethylmagnesium iodide (CF
It is known that 3MgI) is extremely unstable and cannot be used in the trifluoromethylation reaction because Mg has a strong binding force with F and has the property of easily pulling out F and causing the elimination of MgF2. . Among the above-mentioned methods for synthesizing trifluoromethyl group-containing compounds, methods other than the Ullmann reaction require fluorination reagents that are very dangerous and difficult to handle; It is difficult to introduce it arbitrarily.

As a result of intensive study on methods for introducing fluorine-containing aliphatic groups such as trifluoromethyl groups, the present inventor discovered a method for proceeding with the reaction using a process completely different from the above-mentioned synthesis methods, and arrived at the present invention. This is what I did.

That is, the first object of the present invention is to provide a method that allows the fluoroalkylation reaction to proceed easily and safely under normal conditions.

A second object of the present invention is to provide a method for stably synthesizing carbinol having a fluorine-containing aliphatic group such as a trifluoro-methyl group in a high yield. In order to achieve these objects, according to the present invention, the general formula: (However, R represents a fluorine-containing aliphatic group.

) and a fluorine-containing aliphatic iodide represented by the general formula: When both are aliphatic groups, 111!
In the presence of zinc powder, under the action of ultrasonic waves, the carbonyl compound represented by
(first invention), or Snx2 (where X is chlorine, bromine,
Indicates halogen such as iodine.

) in the presence of a tin halide powder represented by: under the action of ultrasound or with the addition of a tertiary amine (second invention)
By reacting and then hydrolyzing this reaction product, a fluorine-containing carbinol represented by the general formula: (where R, , R and R'' are the same as above) is obtained. It is said that

That is, the reaction according to the present invention involves starting materials R, I and R
When reacting with COR'', the zinc powder is in the presence of tin halide powder and the interaction between molecules is strengthened by the action of ultrasonic waves in a reaction vessel, whereby RCOR'' is reacted with zinc powder.
By cross-coupling R and I, fluorine-containing carbinol can be easily synthesized in a stable manner with good yield through the subsequent hydrolysis.

This reaction, for example when using zinc powder (
(Similarly in the case of tin halide powder), it is presumed that the process proceeds as follows. In this case, Zn powder (and/or halogenated soot powder) first reacts with the reactants, especially Rf■ to form stable R, ZnI (and/or R, SrlX2
It is thought that O is produced, and this interacts sufficiently with RCOR'' by the action of the ultrasonic wave to produce the above-mentioned intermediate product.

That is, in the method of the present invention, although the mechanism is currently unclear, as described above, the interaction between the reactant molecules becomes close due to the action of ultrasound, promoting the production of intermediate products as described above; it is conceivable that. Furthermore, when using tin halide, the reaction may be carried out with the addition of a tertiary amine (e.g. pyridine, triethylamine, N,N-dimethylaniline) instead of ultrasonic waves; This is thought to be due to R, Sn coordinating with Sn of IX2 and activating the R'Sn9 bond.Experiments have shown that if ultrasound or tertiary amine is not used as described above, the reaction does not proceed at all. It has been confirmed that be.

At first glance, this reaction appears to be similar to the well-known Grignard reaction, but when Mg or Li is used, RfMgI (or RfLi) itself, which produces the above-mentioned intermediate product, is extremely unstable. It is stable and cannot be used as a synthetic reagent. In other words, Mg or Li has a strong affinity with F, and when Mg (or Li) is reacted with R, I, R, M
MgF2 or LiF is eliminated from gI or RfLi to produce a fluoroalkene. Therefore, Grignard reagents such as RfMgI (or R, Li) cannot be used in the present invention;
Figure 1 illustrates the features or particularities of the method of the present invention for introducing. Furthermore, according to the method of the present invention, each of the starting materials is stable and can be carried out under normal conditions of normal temperature and pressure in a single reaction vessel, making the operation very easy. It's practical.

In the method of the present invention, RrI that can be used has the general formula: CF3(CF2)NI or (CF3)2CF(CF2
) A fluorine-containing aliphatic iodide represented by NI can be mentioned.

This includes CF, I, CF, CF2l, CF3 (CF2
) 21, CF3 (CF2) 31, CF3 (CF2) 41
,CF3(CF2)51,(CF,)2CFI,(CF
3) 2CFCF21, (CF3)2CF(CF2)21
, (CF3)2CF(CF2)31, etc. In addition to these alkyl groups, iodides consisting of unsaturated groups, especially alkenyl groups, such as CF2=CF-CF2l,,CF3
-CF=CFI etc. can also be used. However, the number of carbon atoms in the fluorine-containing aliphatic iodide used is preferably 10 or less in consideration of solubility in a solvent. In addition, the above-mentioned fluorine-containing aliphatic iodides include not only the perfluoroalkyl group or alkenyl group listed above, but also those having a hydrogen atom bonded to a part of the molecular chain, such as CF3 (CF2)2
CH2CF21 can also be used, but in this case it is necessary that F be present adjacent to I. Niodides such as I(CF2CF2)NI can also be used. Furthermore, in addition to the above-mentioned RfI, aromatic group-substituted iodides such as C6H5-CF2l. ．． C6H,
CF2)21 and the like may also be used. RCOR'' used in the method of the present invention includes HCHO, CH
3CHO, C2H5CHO, C3H7CHO, C4H9
CHO,C,HllCHO,CH2=CHCHO,CH
Aliphatic aldehydes such as 3CH=CHCHO, (CH3)2C=CHCHO; C6H5CHO, C6H5CH=C
Aromatic aldehydes such as HCHO, CH3OC6H5CHO; CH3COCH3, CH3COC2H5, (C4H
e) 2C0,CH2=CHCOCH2CH3, (CH3
)2=aliphatic ketone such as CHCOCH3; "7ゝ)C6
Examples include aromatic ketones such as H5COCH=CH2.

R and R'' in this RCOR'' are the same or different atoms or groups, and may be saturated or unsaturated as described above, or may be partially substituted with a substituent. Furthermore, when R and R'' are aliphatic groups, it is desirable that the number of carbon atoms of each of them be 15 or less in consideration of solubility in solvents, and that they together form a ring, for example, a cyclohexyl ring. The above-mentioned zinc powder or Srlx2 powder added in the method of the present invention is added in a molar amount of 1 to 3 with respect to R and I in order to allow the reaction to proceed sufficiently and appropriately.
It is desirable to add in twice the amount.

These metal reagents may be used alone or in combination. When used together, it is desirable that the total amount of zinc powder and Snx2 powder is 1 to 3 times as much in mole as R and I. Furthermore, the reaction proceeds satisfactorily even at room temperature and pressure, and it is sufficient to use ultrasonic waves obtained from a commercially available ultrasonic cleaner.

Further, the tertiary amine that may be added while using tin halide may be, for example, about 1B (volume ratio) of the amount of the solvent used. When using a solvent in the reaction system, an aprotic polar solvent such as dimethyl formaldehyde,
Tetrahydrofuran, dimethylsulfoxide, dimethylacetamide, N-methylpyrrolidone, hexamethylphosphoramide, acetonitrile and the like are preferably 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. In addition, in the method of the present invention,
When the starting material itself is a liquid, it is not necessary to use the above-mentioned solvent. The hydrolysis to obtain carbinol can also be carried out using conventional mineral acids such as H
It may be carried out with Cl, H2SO4. The present inventors have also found that the desired fluorine-containing carbinol can be synthesized stably and in good yield in the following reaction, in addition to the above-mentioned synthesis reaction. That is, as starting materials used,
Instead of RfI described above, R and ZnI are used (third invention), or Rfsnx2l is used (fourth invention: however, in both cases, Rf and X are the same as those described above), and this is R and R'' are the same as described above) and under the action of ultrasound (if R, SrlX2l is used, it may be under the addition of a tertiary amine as described above).

) reaction and then hydrolysis of the product to obtain carbinols similar to those described above. This reaction is performed, for example, when R, ZnI is used (RfSrlX
Similarly, the case of 2l can be expressed as follows. According to this reaction, previously synthesized RfznI or R,SrlX
It is characteristic that 2L is reacted with a carbonyl compound, but in this case as well, the action of ultrasonic waves or tertiary amines strengthens the interaction between the reacting molecules, and the intermediate products such as those mentioned above are It is thought that it promotes the production.

In other words, R, ZnI or R, SnX2l(7)R
, -Zn or Rr-Sn bonds are weakened, and further RCO
It is presumed that the interaction with R'' increases and the reaction between the two proceeds sufficiently.RfZnI or RfS used
Since nX2l itself is highly soluble in the solvent, the reaction proceeds easily.

Moreover, this RrZnI or RfSnX2l has the above-mentioned R,I<l! ．． Zn or SrlX2 (X is the same halogen as above) powder in an autoclave for example 12
It can be synthesized by reacting at 0 to 150°C. The amount of Zn or Snx2 used in this case is Rf
It is desirable that the number of moles is 1 to 3 times that of I. Zn and Snx2 can be used together at the same time, but the total amount is R, I
It is also desirable that the number of moles is 1 to 3 times that of the amount of carbon dioxide. Note that the solvent used in the reaction and the reaction conditions with the carbonyl compound are the same as those described above.

The fluorine-containing carbinol synthesized by the method of the present invention can be used for various purposes as described below, and is extremely useful. (1) It can itself be used as a solvent.

(2) It can be used as a synthetic intermediate for water and oil repellents, medicines, agricultural chemicals, dyes, pigments, surfactants, etc.

(3) It can be used as a raw material for monomers for producing fluoropolymers. For example, an OH group and an adjacent hydrogen atom are removed by a dehydration reaction to form an unsaturated bond in the monomer. Next, the present invention will be described in more detail with reference to examples, but the following examples do not limit the present invention, and various modifications can be made based on the technical idea thereof.

Example 1 Commercially available zinc powder 1 in an eggplant-shaped flask (capacity 50 m1)
．． 30y (0.02 gram atom), trifluoromethyl iodide 2.15y (11mm0), benzaldehyde 1
．． 06y (10 mm diameter) and 25 ml of dimethylformamide dried with a molecular sieve were added, and the three powders were reacted in a water bath under the action of ultrasonic waves using a commercially available ultrasonic cleaner (35w132 KHz).

After the reaction, 100 ml of 2% hydrochloric acid was added to perform hydrolysis, and the resulting oil layer was extracted with diethyl ether. After drying this extract over magnesium sulfate, the solvent was distilled off. By distilling the residue under reduced pressure, phenyltrifluoromethycarbinol 0ゞ゛3〉σ/kugo2 was reduced to 72% (
The yield was 1.27 V).

The boiling point of this carbinol is 105-108℃/16n1
It was mHg. Example 2 In Example 1, tetrahydrofuran 25 was used as the solvent.
As a result of reaction using m1 under the same conditions, phenyltrifluoromethicarbinol was 56% (a). It was obtained in a yield of 99f).

Example 3 Commercially available zinc powder 1 in an eggplant-shaped flask (capacity 50 m1)
．． 30f (0.02 gram atom), trifluoromethyl iodide 2.15f (11mm), acetophenone 1.
20y (10mm) and dimethylformamide 25
ml, respectively, and put them in a commercially available ultrasonic cleaner (35W) in a water bath.
The reaction was carried out for 1 hour under the action of ultrasound (132 KHz).

After the reaction, 100 ml of 2% hydrochloric acid was added, and the oil layer was extracted with diethyl ether. After drying this extract over magnesium sulfate, the solvent was distilled off. By distilling the residue under reduced pressure, methylphenyltrifluoromethylcarbinol 5f3>Z<] was obtained in a yield of 55% (1.05 g). The boiling point of this carbinol is 81-83)C/3m
The temperature was 1 mHg. Example 4 In Example 3, 25 ml of tetrahydrofuran was used as the solvent and the reaction was carried out under the same conditions. It was obtained in a yield of 82y).

Examples 5 to 9 In Example 1, the carbonyl compound used was C5H
llCHO (Example 5), CH3CH=CHCHO (Example 6), C6H5-CH=CHCHO (Example 7),
(Example 9) and reacted under the same conditions, various carbinols shown in Table 1 below were obtained.

The structures of each carbinol, including those of Examples 1 and 2, were identified by IR and NMR spectral analysis. Examples 10 to 17 In Example 1, the fluorine-containing aliphatic iodide and carbonyl compound shown in Table 2 below were used, and the reaction was carried out under the same conditions except for the following.

The amount used was 11 mm01 for the fluorine-containing aliphatic iodide and 10 n1 m01 for the carbonyl compound. for example,(
When using CF3)2CFI, (CF3)2CFI is set to 3.26f (11mm01), and phenyl (heptafluoro-1-methylethyl) carbinol is extracted by vacuum distillation of the reaction product. % (1.49y), and the boiling point was 120-123°C/104mmHg. The reactants and the properties of the produced carbinol for each example are summarized in Table 2 below. Example 18 In Example 1, tin chloride (SnC) was used instead of zinc powder.
12) under the same conditions while applying ultrasound, and the reaction product was hydrolyzed to obtain the same phenyltrifluoromethyl carbinol.

Example 19 In Example 18, 5 ml of pyridine was added instead of applying ultrasound, the reaction was carried out under the same conditions, and the reaction product was hydrolyzed to obtain the same phenyltrifluoromethyl carbinol.

The yield of this carbinol is 18% and the boiling point is 92-95℃
/26mmHg. Comparative Example For comparison, a reaction was carried out under exactly the same conditions as in Example 1, except that magnesium powder was used instead of zinc powder, and it was confirmed that the desired fluorine-containing carbinol was not produced at all.

This result was similar when lithium powder was used. Example 20 Predetermined amounts of trifluoromethyl iodide and zinc powder were placed in an autoclave and reacted while heating at 120 to 15 CfC to obtain CF3ZnI.

As in Example 1, this was placed in a flask together with benzaldehyde and dimethylformamide, and ultrasonic waves were applied in a water bath. After the reaction, 100 ml of 2% hydrochloric acid was added, and the resulting oil layer was extracted, further dried and then distilled under reduced pressure to obtain the same phenylalkyl carbinol as in Example 1. Note that when RfZnI other than the above-mentioned CF3ZnI was used, corresponding carbinols were obtained. Example 21 In Example 20, tin chloride (Sn
Cl2) was reacted in the same manner as trifluoromethyl iodide, and CF3SnCl. I got I.

Subsequently, in the same manner as in Example 20, benzaldehyde and dimethylformamide were placed in a flask and reacted while applying ultrasound, and the product extracted from the resulting oil layer was hydrolyzed to produce phenyltrifluoromethylcarbinol. Obtained. Example 22 In Example 21, the reaction was carried out with the addition of 5 mt of pyridine instead of applying ultrasound, and the same phenyltrifluoromethyl carbinol was obtained by hydrolysis of the reaction product.

Claims (1)

[Claims] 1 A fluorine-containing aliphatic iodide represented by the general formula: R_fI (where R_f represents a fluorine-containing aliphatic group) and a fluorine-containing aliphatic iodide represented by the general formula: RCOR' (however, R and R' are , the same or different atoms or groups selected from the group consisting of hydrogen atoms, aliphatic groups, and aromatic groups, which can jointly form a ring when both are aliphatic groups). By reacting the represented carbonyl compound under the action of ultrasound in the presence of zinc powder and then hydrolyzing this reaction product, the general formula: ▲Mathematical formula, chemical formula, table, etc.▼ A method for producing a fluorine-containing carbinol, the method comprising obtaining a fluorine-containing carbinol represented by R_f, R and R' are the same as those described above. 2. The method according to claim 1, wherein R_f is a fluorine-containing alkyl group or a fluorine-containing alkenyl group having 10 or less carbon atoms. 3. Item 1 or 2 of the claims, wherein R and R' are an alkyl group or an alkenyl group having 15 or less carbon atoms.
The method described in section. 4. The method according to any one of claims 1 to 3, wherein the number of moles of zinc powder is used in a range of 1 to 3 times R_fI. 5 Items 1 to 4 of the claims, in which a fluorine-containing aliphatic iodide and a carbonyl compound are reacted using a solvent.
The method described in any one of the paragraphs. 6. The method according to claim 5, wherein an aprotic polar solvent is used as the solvent. 7. The method according to any one of claims 1 to 6, wherein the reaction is carried out at normal temperature and pressure. 8 A fluorine-containing aliphatic iodide represented by the general formula: R_fI (where R_f represents a fluorine-containing aliphatic group) and a fluorine-containing aliphatic iodide represented by the general formula: RCOR' (however, R and R' are a hydrogen atom, an aliphatic group The same or different atoms or groups selected from the group consisting of groups and aromatic groups, which can jointly form a ring when both are aliphatic groups. , SnX_2 (however,
X represents halogen. ) by reacting under the action of ultrasound or with the addition of a tertiary amine in the presence of a tin halide powder of the general formula: ▲mathematical formula, There are chemical formulas, tables, etc. ▼ A method for producing fluorine-containing carbinol, which is characterized by obtaining fluorine-containing carbinol represented by the following formula (where R_f, R and R' are the same as above). 9. The method according to claim 8, wherein R_f is a fluorine-containing alkyl group or a fluorine-containing alkenyl group having 10 or less carbon atoms. 10 Item 8 or 9 of the claims, wherein R and R' are an alkyl group or an alkenyl group having 1 or less carbon atoms.
The method described in section. 11. The method according to any one of claims 8 to 10, wherein the tin halide powder is used in a mole range of 1 to 3 times R_fI. 12. The method described in any one of claims 8 to 11, which comprises reacting a fluorine-containing aliphatic iodide and a carbonyl compound using a solvent. 13. The method according to claim 12, wherein an aprotic polar solvent is used as the solvent. 14. The method according to any one of claims 8 to 13, wherein the reaction is carried out at normal temperature and pressure. 15 A fluorine-containing aliphatic iodide represented by the general formula: R_fZnI (where R_f represents a fluorine-containing aliphatic group) and a fluorine-containing aliphatic iodide represented by the general formula: RCOR' (however, R and R' are a hydrogen atom, an aliphatic group The same or different atoms or groups selected from the group consisting of groups and aromatic groups, which can jointly form a ring when both are aliphatic groups. By reacting under the action of ultrasound and then hydrolyzing this reaction product, the general formula: ▲Mathematical formula, chemical formula, table, etc.▼ (However, R_f, R and R' are as mentioned above. A method for producing a fluorine-containing carbinol, characterized by obtaining a fluorine-containing carbinol represented by 16. The method according to claim 15, wherein R_f is a fluorine-containing alkyl group or a fluorine-containing alkenyl group having 10 or less carbon atoms. 17. The method according to claim 15 or 16, wherein R and R' are an alkyl group or an alkenyl group having 15 or less carbon atoms. 18 Claims 15 to 18, in which a fluorine-containing aliphatic iodide and a carbonyl compound are reacted using a solvent.
The method described in any one of paragraph 17. 19. The method according to claim 18, wherein an aprotic polar solvent is used as the solvent. 20. The method according to any one of claims 15 to 19, wherein the reaction is carried out at normal temperature and pressure. 21 After generating R_fZnI by reacting a fluorine-containing aliphatic iodide represented by the general formula: R_fI (where R_f represents a fluorine-containing aliphatic group) and zinc powder under heating. , the method described in any one of claims 15 to 20, which comprises reacting this R_fZnI with a carbonyl compound. 22. The method according to claim 21, wherein zinc powder is used in an amount of 1 to 3 times R_fI in terms of moles. 23 A fluorine-containing aliphatic iodide represented by the general formula: R_fSnX_2I (wherein, R_f is a fluorine-containing aliphatic group and X is a halogen), and a fluorine-containing aliphatic iodide represented by the general formula: RCOR' (however, R and R' are hydrogen atoms) , the same or different atoms or groups selected from the group consisting of aliphatic groups and aromatic groups, which can jointly form a ring when both are aliphatic groups. By reacting with a carbonyl compound under the action of ultrasound or adding a tertiary amine, and then hydrolyzing this reaction product, the general formula: ▲Mathematical formula, chemical formula, table, etc.▼ , R_f, R and R' are the same as those described above). 24. The method according to claim 23, wherein R_f is a fluorine-containing alkyl group or a fluorine-containing alkenyl group having 10 or less carbon atoms. 25. The method according to claim 23 or 24, wherein R and R' are an alkyl group or an alkenyl group having 15 or less carbon atoms. 26 Claims 23-- in which a fluorine-containing aliphatic iodide and a carbonyl compound are reacted using a solvent.
The method described in any one of paragraph 25. 27. The method according to claim 26, wherein an aprotic polar solvent is used as the solvent. 28. The method according to any one of claims 23 to 27, wherein the reaction is carried out at normal temperature and pressure. 29 A fluorine-containing aliphatic iodide represented by the general formula: R_fI (where R_f represents a fluorine-containing aliphatic group) and SnX_2 (
However, X represents halogen. ) by reacting with a tin halide powder represented by R_fSnX under heating.
After producing _2I, the R_fSnX_2I and a carbonyl compound are reacted.
The method described in any one of Items 1 to 28. 30. The method according to claim 29, wherein the tin halide powder is used in a molar amount ranging from 1 to 3 times R_fI.