JP3482720B2 - Method for producing N-fluoropyridinium sulfonate - Google Patents

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing N-fluoropyridinium sulfonate. The N-fluoropyridinium sulfonate produced in the present invention is useful as a so-called fluorinating agent, a reagent for introducing a fluorine atom into an organic compound such as an aromatic compound, an alkene, an enol silyl ether, a carbanion or an active methylene compound. [Journal of the American Chemical Society (J. Am. Chem. Soc., 1990,
112 , 8563 and JP-B-2-33707, JP-A-5-294937, and JP-A-3-99062].

[0002]

2. Description of the Related Art As a method for producing N-fluoropyridinium sulfonate, a method of reacting fluorine with a pyridinesulfonic acid compound in acetonitrile or hydrous acetonitrile has been reported.
In JP 3707 and JP-A 5-294937, as solvents that can be used, water, propionitrile, acetone, chloroform, methylene chloride, carbon tetrachloride, trichlorofluoromethane, trichlorotrifluoroethane, ethyl acetate are further used. , Diethyl ether, or tetrahydrofuran are indicated.

[0003]

However, when a pyridinesulfonic acid compound having a salt structure is used as a raw material, the solubility in most of the above solvents other than water is extremely low in many cases. Therefore, when the above-mentioned solvent other than water is used as the reaction solvent, the yield is remarkably reduced, and thus a large amount of solvent is required. However, the use of large amounts of solvent is very expensive for product isolation. Further, the N-fluoropyridinium salt in which the electron-withdrawing group is substituted on the pyridine nucleus is gradually or promptly decomposed by water depending on the position of the substituent and its electron-withdrawing property. The method using water as the reaction solvent is not a general-purpose method. The method using hydrous acetonitrile as a reaction solvent is also limited to the production of N-fluoropyridinium salt which does not decompose under the production conditions due to water contained in hydrous acetonitrile. As described above, none of the conventional methods is sufficient in terms of cost, operability or versatility.

[0004]

In order to solve these problems, the present invention has conducted extensive studies and, as a result, has found that polyfluoro lower aliphatic alcohol, which can be easily reused, is used in the fluorination of pyridinesulfonic acid compounds. When used as a solvent, the starting pyridinesulfonic acid compound can be easily dissolved in this alcohol, and the fluorination of the pyridinesulfonic acid compound progresses efficiently and easily, and it is useful as a fluorinating agent. The inventors have found that nates can be produced in high yield, and have completed the present invention. That is, according to the present invention, in the polyfluoro lower aliphatic alcohol, the general formula:

[0005]

[Chemical 3]

[Wherein R ^{1 to} R ⁴ are the same or different,
A hydrogen atom, a halogen atom, an alkyl group, an aryl group, a nitro group, a cyano group, an alkoxy group or an aryloxy group; R is a single bond or an alkylene group; M is a hydrogen atom, a metal atom or ammonium. ] By reacting a pyridinesulfonic acid compound represented by

[0007]

[Chemical 4]

[In the formula, R ^{1 to} R ⁴ and R have the same meaning as described above. ] N-fluoro pyridinium sulfonate shown by these is manufactured.

In the present invention, the alkyl group is preferably a substituted or unsubstituted alkyl group having 1 to 8 carbon atoms, more preferably 1 to 4 carbon atoms. For example, as an unsubstituted alkyl group, CH ₃ , CH ₃ CH ₂ , CH ₃ CH ₂ CH ₂ , (C
_{H 3) 2 CH, CH 3} (CH 2) 2 CH 2, (CH 3) 2 CHCH 2,
(CH ₃ ) ₃ C, CH ₃ (CH ₂ ) ₃ CH ₂ , CH ₃ (CH ₂ ) ₄ C
A linear or branched alkyl group such as H ₂ , CH ₃ (CH ₂ ) ₅ CH ₂ , CH ₃ (CH ₂ ) ₆ CH ₂ or the like can be shown.

Preferred examples of the substituent of these alkyl groups include a halogen atom, an alkoxy group and an acyloxy group. As the substituted alkyl group, for example, CH
₂ F, CHF ₂ , CF ₃ , CH ₃ CFH, CH ₂ FCH ₂ , C
_{H 3 CF 2, CHF 2 CH} 2, CF 3 CH 2, CF 3 CF 2, C
F ₃ CF ₂ CF ₂ , (CF ₃ ) ₂ CF, CF ₃ (CF ₂ ) ₂ CF ₂ ,
(CF ₃ ) ₂ CFCF ₂ , CF ₃ CF ₂ (CF ₃ ) CF, CH ₂ C
l, CHCl ₂ , CCl ₃ , CFCl ₂ , CF ₂ Cl, CH ₂ Cl
CH ₂ , CCl ₃ CH ₂ , CCl ₃ CCl ₂ , CH ₂ Br, CHB
r ₂ , CBr ₃ , CF ₂ Br, CF ₂ HCF ₂ , CF ₂ ICF ₂ ,
CF ₂ BrCF ₂ , CF ₂ ClCF ₂ , CF ₂ HCF ₂ CF ₂ , CF
₂ ClCF ₂ CF ₂ , CF ₂ ICF ₂ CF ₂ , (CF ₃ ) ₂ CH,
(CF ₃ ) ₂ CCl, CF ₂ H (CF ₂ ) ₂ CF ₂ , CF ₂ Cl (CF
₂ ) ₂ CF ₂ , CF ₂ Br (CF ₂ ) ₂ CF ₂ , CF ₂ I (CF ₂ ) ₂ C
A linear or branched substituted alkyl group such as F ₂ , CH ₃ OCH ₂ and CH ₃ OCOCH ₂ can be shown.

The aryl group preferably has 6 to 1 carbon atoms.
0, more preferably 6-8 substituted or unsubstituted aryl groups, such as C ₆ H ₅ , CH ₃ C ₆ H ₄ , (CH ₃ ) ₂ C ₆
H ₄ , C ₆ H ₄ Cl, C ₆ H ₄ F and the like can be mentioned. The alkoxy group preferably has 1 to 8 carbon atoms, and more preferably 1
~ 4 substituted or unsubstituted alkoxy group, for example,
CH ₃ O, CH ₃ CH ₂ O, CH ₃ CH ₂ CH ₂ O, (CH ₃ ) ₂
CHO, CH ₃ (CH ₂ ) ₂ CH ₂ O, (CH ₃ ) ₂ CHCH
₂ O, C ₆ H ₅ CH ₂ O, CF ₃ CH ₂ O, HCF ₂ CF ₂ CH
₂ O and the like. The aryloxy group is preferably a substituted or unsubstituted aryloxy group having 6 to 10 carbon atoms, more preferably 6 to 8 carbon atoms, for example, C ₆ H ₅ O,
_{CH 3 C 6 H 4 O,} (CH 3) 2 C 6 H 3 O, ClC 6 H 4 O, FC
₆ H ₄ O and the like.

R is a single bond or preferably 1 to 5 carbon atoms.
Is an alkylene group. As the alkylene group, for example,
_{-CH 2 -, - CH 2 CH} 2 -, - CH 2 CH 2 CH 2 -, -
_{CH 2 (CH 2) 2 CH} 2 -, - CH 2 (CH 2) 3 CH 2 -, - C
_{H (CH 3) -, -} CH (CH 3) CH 2 - and the like.

M is a hydrogen atom, a metal atom or an ammonium group. The metal atom is preferably an alkali metal atom or an alkaline earth metal atom, and for example, potassium, sodium, lithium, calcium, magnesium and the like are particularly preferable. When the metal atom is an alkaline earth metal atom (M '), it is expressed as M = (1/2) M'. Ammonium is, for example, NH ₄ , NH (C _{2
H 5) 3, NH 2 (} C 2 H 5) 2, NH 3 (C 2 H 5), N (C
₂ H ₅ ) ₄ , NH (CH ₃ ) ₃ , NH ₂ (CH ₃ ) ₂ , NH ₃ CH ₃ ,
_{NH 3 (C 3 H 7)} , NH 3 (C 4 H 9), NH 3 CH 2 C 6 H 5, N
_{(CH 3) 3 (CH 2} C 6 H 5) or N (C ₄ H _{9) 4} and the like, _{^{further, R 5 -N (CH 3)}} 3, R 5 -N (CH 3) 2 H, R ^5- N (C
_{2 H 5) 2 H, R} 5 -N (C 4 H 9) 2 H ( wherein, R ⁵ is an organic polymer chain) such as can also be exemplified. Preferable examples of the organic polymer chain include a polyethylene chain, a polystyrene chain and a polyacrylic chain.

The pyridinesulfonic acid compound (II) in which M is a metal atom is obtained by adding potassium hydroxide, sodium hydroxide, lithium hydroxide or calcium hydroxide to the above pyridinesulfonic acid compound (II) in which M is a hydrogen atom. , Easily obtained by reacting a corresponding metal hydroxide such as magnesium hydroxide or the like, or a corresponding metal hydride such as potassium hydride, sodium hydride, lithium hydride, calcium hydride or magnesium hydride. .

The above pyridinesulfonic acid compound (II) in which M is ammonium is obtained by adding NH ₃ , N (C) to the above pyridinesulfonic acid compound (II) in which M is a hydrogen atom.
_{2 H 5) 3, NH (} C 2 H 5) 2, NH 2 (C 2 H 5), N (CH 3) 3,
NH ₂ (C ₃ H ₇ ), NH ₂ (C ₄ H ₉ ), NH ₂ CH ₂ C ₆ H ₅ , N
(C ₄ H _{9) 3} or ^{_{R 5 -N (CH 3) 2}} , R 5 -N (C
₂ H ₅ ) ₂ , R ⁵ —N (C ₄ H ₉ ) ₂ (where R ⁵ has the same meaning as described above), or NH ₄ OH, N (C ₂ H ₅ ) _{4
OH, NH (C 2 H 5} ) 3 OH, NH 2 (C 2 H 5) 2 OH, N (C
_{H 3) 4 OH, NH 3} (C 3 H 7) OH, NH 3 (C 4 H 9) OH,
_{N (CH 3) 3 (CH} 2 C 6 H 5) OH, N (C 4 H 9) 4 OH or R
^{_{5 -N (CH 3) 3 OH}} , R 5 -N (C 2 H 5) 3 OH, R 5 -N
It can be easily obtained by acting an ammonium hydroxide or the like such as (C ₄ H ₉ ) ₃ OH (wherein R ⁵ has the same meaning as described above).

The above pyridinesulfonic acid compound (II) in which M is a hydrogen atom exists as an ion represented by the following formula (III).

[0017]

[Chemical 5]

[In the formula, R ^{1 to} R ⁴ and R have the same meanings as described above. ]

The pyridinesulfonic acid compound (II) and the polyfluoro lower aliphatic alcohol used in the production method of the present invention are industrially easily available or easily synthesized compounds. Examples of the polyfluoro lower aliphatic alcohol include trifluoroethanol, pentafluoropropanol, tetrafluoropropanol, hexafluoropropanol, hexafluorobutanol, nonafluorobutanol, octafluoropentanol and the like. These alcohols may contain straight chain or branched chain, and further each isomer depending on the substitution position of the fluorine atom, and they can be used alone or as a mixture of two or more kinds.

The reaction temperature is usually at least the melting point of the polyfluoro lower aliphatic alcohol used as the solvent, the boiling point or 6
Can be selected from the temperature range up to 0 ℃, -40 ℃ ~ 4
The range of 0 ° C. is preferable in terms of economic efficiency and good reaction yield.

The fluorine used in the production method of the present invention may be used as it is, but in order to control the violent reaction of fluorine, fluorine is diluted to 1 to 75% by volume with an inert gas before use. Preferably. Examples of the inert gas include nitrogen, helium, argon and the like.

In order to carry out the reaction in good yield, the amount of fluorine used is at least equimolar to the pyridinesulfonic acid compound, but since it varies depending on the method of introducing fluorine, the reaction temperature, the reaction apparatus, etc., pyridinesulfone is used. The amount of fluorine required for the acid compound to react with fluorine and disappear may be appropriately selected.

N- produced by the production method of the present invention
Examples of the fluoropyridinium sulfonate (I) include the following.

[0024]

[Chemical 6]

[0025]

[Chemical 7]

[0026]

[Chemical 8]

[0027]

[Chemical 9]

[0028]

[Chemical 10]

[0029]

[Chemical 11]

[0030]

[Chemical 12]

[0031]

[Chemical 13]

[0032]

[Chemical 14]

[0033]

[Chemical 15]

[0034]

[Chemical 16]

[0035]

[Chemical 17]

[0036]

[Chemical 18]

[0037]

[Chemical 19]

[0038]

[Chemical 20]

[0039]

[Chemical 21]

[0040]

[Chemical formula 22]

[0041]

EFFECTS OF THE INVENTION According to the production method of the present invention, N-fluoropyridinium sulfonate (I) useful as a fluorinating agent can be produced in good yield, and the polyfluoro lower aliphatic alcohol used as a solvent can be recovered. Is easy.

[0042]

EXAMPLES The present invention will be described in more detail below with reference to examples. Example 1

[Chemical formula 23] 40 ml of 1,1,1,3,3,3-hexafluoro-2-propanol, 3.18 g of 3-pyridinesulfonic acid (20 mmo
l) and amine resin (ion exchange resin Amberlite I)
RA-94S. Organo Co., Ltd. manufacturing) 10g (-N
A mixed gas of fluorine and nitrogen (volume ratio 1: 9) was introduced at a flow rate of 45 ml / min into a container mixed with (CH ₃ ) ₂ : 20 mmol) at 0 ° C. while stirring. The number of moles of introduced fluorine was 61.5 mmol. Then, nitrogen was flowed to remove residual fluorine, and the reaction solution was filtered. The filtrate was concentrated with an evaporator and then dried under reduced pressure. Acetonitrile was added to the residue, and the precipitated crystals were separated by filtration to give N-fluoropyridinium-3-sulfonate (3.07 g). Yield 8
7%. The manufacturing conditions are shown in Table 1 and the properties of the product are shown in Table 2.

Examples 2 and 3 The reaction was carried out in the same manner as in Example 1 except that the pyridine sulfonic acid compound, polyfluoro lower aliphatic alcohol and amine resin shown in Table 1 were used and the conditions shown in Table 1 were used. It was The properties of the product obtained are shown in Table 2.

[0044]

[Table 1]

[0045]

[Table 2]

Example 4

[Chemical formula 24] 40 ml of 1,1,1,3,3,3-hexafluoro-2-propanol and sodium 4-pyridinesulfonate 1.84
Into a container in which g (10.19 mmol) was mixed, a mixed gas of fluorine and nitrogen (volume ratio 1: 9) was introduced at a flow rate of 45 ml / min while stirring at 0 ° C. The number of moles of introduced fluorine was 30.8 mmol. Then, after flushing nitrogen to remove the residual fluorine, trifluoroacetic acid 20 was added to the reaction solution.
ml was added. The reaction solution was concentrated with an evaporator and then dried under reduced pressure. Acetonitrile was added to the residue, and the precipitated crystals were filtered out to obtain 1.34 g of N-fluoropyridinium-4-sulfonate. Yield 74%. The production conditions are shown in Table 3 and the properties of the product are shown in Table 4.

Examples 5 to 8 The reaction was carried out in the same manner as in Example 4 except that the pyridine sulfonic acid compound and polyfluoro lower aliphatic alcohol shown in Table 3 were used and the conditions shown in Table 3 were used. The properties of the product obtained are shown in Table 4. In addition, Examples 5 and 6
Then, after the fluorination reaction, the reaction solution was directly concentrated and dried under reduced pressure to obtain a corresponding N-fluoropyridinium sulfonate compound. In Examples 7 and 8, after the fluorination reaction, the reaction solution was concentrated, Acetonitrile was added to the residue for extraction, the extract was filtered, concentrated and dried under reduced pressure to obtain the desired N-fluoro-4-methylpyridinium-2-sulfonate.

[0048]

[Table 3]

[0049]

[Table 4]

─────────────────────────────────────────────────── ─── Continuation of front page (56) References JP-A-5-125050 (JP, A) JP-A-4-235969 (JP, A) JP-A-2-231474 (JP, A) (58) Field (Int.Cl. ⁷ , DB name) C07D 213/89 C07B 39/00 CA (STN) REGISTRY (STN)

Claims (3)

(57) [Claims] 1. A polyfluoro lower aliphatic alcohol,
General formula: [Wherein R ^{1 to} R ⁴ are the same or different and each is a hydrogen atom, a halogen atom, an alkyl group, an aryl group, a nitro group, a cyano group, an alkoxy group or an aryloxy group; R is a single bond or an alkylene group; Represents a hydrogen atom, a metal atom or ammonium. ] The pyridine sulfonic acid compound represented by [In the formula, R ^{1 to} R ⁴ and R are as defined above. ] The manufacturing method of N-fluoro pyridinium sulfonate shown by these. 2. The production method according to claim 1, wherein a polyfluoro lower aliphatic alcohol having 2 to 5 carbon atoms is used as the polyfluoro lower aliphatic alcohol. 3. The polyfluoro lower aliphatic alcohol is
The at least one polyfluoro lower aliphatic alcohol selected from the group consisting of trifluoroethanol, tetrafluoropropanol, pentafluoropropanol, hexafluoropropanol, hexafluorobutanol, nonafluorobutanol and octafluoropentanol. The manufacturing method described.