JPH0399062A - N-fluoropyridinium sulfonate - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I. EXAMPLE:N-Fluoropyridinium-2-sulfonate. USE:A fluorinating agent. The compound expressed by formula I is readily produced and excellent in selectivity of reaction. PREPARATION:A pyridinesulfonic acid compound expressed by formula II (M is H or metal atom) is reacted with fluorine, preferably fluorine gas in a solvent such as acetonitrile at -45 deg.C to ambient temperature to provide the compound expressed by formula I. The compound expressed by formula I has extremely high usefulness on industry, because the compound regenerates pyridinesulfonic acid compound which is a production raw material after reacting as a fluorinating agent.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to N-fluoropyridinium-sulfonates represented by the general formula. N-fluoroviridinium-sulfonate is useful as a fluorinating agent (fluorine atom-introducing agent) because it is easy to produce and has extremely high reaction selectivity. [Prior Art] The present inventor has reported N-fluoropyridinium salts represented by N-fluoropyridinium trifluoromethanesulfonate as useful fluorination agents (Tstra
hedron Lett. , 27.4465 (1986
), and Japanese Patent Application Laid-Open No. 63-10764]. However, when this fluorinating agent is used, it cannot be said that the regioselectivity of the reaction is necessarily sufficient. For example, N-
When phenol is fluorinated using fluoroviridinium trifluoromethanesulfonate, the three precepts of 0-fluorophenol, p-fluorophenol, and 2,4-difluorophenol are active (JP-A-63-1).
0764 Reference Example 1), and in the fluorination of steroids, when used as a trimethylsilyl enol ether derivative, it can be used as a physiologically active substance! ! Not only 6-fluorosteroids fluorinated at the essential 6th position, but also 4-fluorosteroids fluorinated at the 4th position were produced, and the ratio was 2.3! 10764 Reference Example 37). Separating and purifying each isomer requires complicated steps, so economic production efficiency is low. Therefore, a method of producing multiple isomers is clearly not preferred. In addition, the present inventors reported N-fluoro-6-chloroviridinium-2-sulfonate as a fluorinating agent with excellent regioselectivity in fluorination reactions [Preliminary paper of the 14th Fluorine Chemistry Symposium [Refer to Collection (1st year of Heikai)], the defect was that the production yield of 6-chloropyridine-2-sulfonic acid, which was the raw material for the fluorination agent, was low. [What the invention aims to solve] [ff1] In order to solve the above-mentioned industrially important problems, the present inventors have
As a result of intensive research, the N-fluoropyridinium-sulfonate of the present invention was synthesized using industrially easily available raw materials, although it does not have an electron-withdrawing group called a chlorine atom on the pyridine ring. The present invention has been brought to fruition by discovering that it can be a fluorinating agent with sufficient reaction activity and excellent regioselectivity. For example, the N-fluoroviridinium-2-sulfonate of the present invention efficiently produces only O-fluorophenol when phenol is fluorinated, and in the case of fluorinated steroids mentioned above, it can be used under mild conditions. 6-fluorosteroid was selectively administered (Reference Example 1 below)
and 2 reference R). N-fluoropyridinium-sulfonate represented by the general formula (1) is a pyridine sulfonic acid compound represented by the general formula N (wherein M is a hydrogen atom or a metal atom), in which fluorine (F , ). When M in general formula (n) is a metal atom, an alkali metal is preferable. General formula ([1)
The pyridine sulfonic acid compound represented by is an industrially easily available compound, such as 2-pyridine sulfonic acid, 3-pyridine sulfonic acid, 4-pyridine sulfonic acid,
Lithium 2-pyridine sulfonate, sodium 2-pyridine sulfonate, potassium 2-pyridine sulfonate, 3
-Sodium pyridine sulfonate, sodium 4-pyridine sulfonate, and the like. In order to control the violent reaction of the fluorine used in the present invention, it is preferable to use fluorine gas diluted with an inert gas so that the volume of the inert gas is 99.9% to 50%. Examples of the inert gas include nitrogen, helium, and argon. In order to carry out the reaction with good yield, the amount of fluorine used varies depending on the introduction method, reaction temperature, reaction solvent, substrate solubility, reaction equipment, etc., but is generally at least equimolar to the substrate. It is preferable to use a reaction solvent in this reaction, and examples of the reaction solvent include acetonitrile and hydrous acetonitrile. The anti-core temperature can be selected from a range of -45°C to room temperature, or preferably -40°C to 0°C to improve reaction efficiency and yield. [Effect of the invention] As shown above, N represented by the general formula (1) of the present invention
-Fluoroviridinium-sulfonate is a fluorinating agent that is easy to produce and has extremely excellent regioselectivity. Furthermore, after this reagent reacts as a fluorinating agent, the pyridine sulfonic acid compound, which is the raw material for its production, is regenerated, so it can be said to be extremely useful industrially. The present invention will be explained in more detail below using Examples and Reference Examples. Example 1 F2-pyridine sulfonic acid 477w (3.0mmo
+) in 6.6 ml of a mixed solvent of water and acetonitrile (1:10), and then cooled to -25°C.

While stirring, a mixed gas of fluorine and nitrogen (1:9) was introduced at a flow rate of 40 ml/min to cause a reaction. The amount of fluorine introduced was 9 mmol. After the reaction was completed, 20 ml of tetrahydrofuran was added to bring the temperature to room temperature, and the precipitated crystals were filtered off and dried. The amount of N-fluorobiridinium-2-sulfonate obtained was 427 ml (yield: 8 l%). Purification was performed by recrystallization from acetonitrile. The physical property values and spectral data are shown below. Decomposition point! 32-235℃. 19F-NMR (CFCh internal standard in 1 l acetonitrile): -41.2 ppm (bs, NF). 'If-NMR (400 MILz,! in acetonitrile) 2 δ8.11 (IH4.5-H). 8.50 (1fl
．． ddd, J-7.6, 6.5.2.2Hz, 3-H)
, 8.61 (IH. tdd, J-7.6.
1.5, IHz, 4-H), 9.04(IH, d
dd. J-14.5.7.0, 111z. 6-H). M
Ass! a/e 177(M'). Elemental analysis (Ii
I: Actual value: C. 33.982; lI. 2.28X;N
, 7.95X. Calculated value: C, 33.90X; H, 2.2
8$; N, 7.91X. Example 2 Reference Example l P Water-A7tonitrile (1:10) mixed solvent 2.
1 mmol of sodium 2-pyridine sulfonate was added to 2 ml, and a mixed gas of fluorine and nitrogen (1:9) was introduced at a flow rate of 30 ml/min at -25°C. The total amount of fluorine introduced was 9 mmo+. After the reaction, 20 ml of tetrahydrofuran was added and the precipitate precipitated was collected by filtration, and the obtained precipitate was extracted with acetonitrile. By evaporating the solvent, 68N (38%) N-fluoropyridinium-2-sulfonate was obtained from the extract. The spectral data was completely inferior to that obtained in Example 1. Drying 1,1.2-
}Lichloroethane 2ml, Phenol 5 3.0mg
(0.56 mmol), and N-fluoroviridinium-2-sulfonate 99.7■ (0.56 mmol
) was refluxed for 1.5 hours under an argon atmosphere. Gas chromaphenol and 2,4-difluorophenol were not detected in the reaction solution. Reference Example 2 The spectral data of the raw material matched that of the standard sample. In addition, 4-fluoro-5-androsten-l7β-ol-3-one produced by fluorination at the 4-position is
Only traces were found in the F-NMR spectrum of the crude reaction product before purification.On the other hand, 6
Regarding the steric configuration of the fluorine atom, the ratio of 2/β of the obtained biobottom was 1/3.

Claims (1)

[Claims] general formula ▲Contains mathematical formulas, chemical formulas, tables, etc.▼ N-fluoropyridinium-sulfonate represented by: