JPH0410468B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the structural formula A new substance N-trifluoromethyl-
It relates to N-nitrosotrifluoromethanesulfonamide. The N-trifluoromethyl-N-nitrosotrifluoromethanesulfonamide of the present invention is useful as a trifluoromethyl group-introducing reagent. It is well known that the trifluoromethyl group is an important functional group in the synthesis of medicines and agricultural chemicals. ]. For example, by reacting the N-trifluoromethyl-N-nitrosotrifluoromethanesulfonamide of the present invention with readily available β-mercaptopropionic acid, β-
This can lead to trifluoromethylthiopropionic acid [see US Pat. No. 3,522,293]. Conventionally, as basic methods for introducing a trifluoromethyl group, (1) a method of converting a functional group into a trifluoromethyl group, and (2) a method of using a trifluoromethyl group-introducing reagent are known. A typical example of (1) is a method in which a desired methyl group is converted into a trichloromethyl group using chlorine gas, and then reacted with hydrogen fluoride such as antimony pentafluoride or in the presence of a metal catalyst to convert it into a trifluoromethyl group. A method of converting a carboxyl group to a trifluoromethyl group by treating it with sulfur tetrafluoride [e.g., Helv.Chim.Acta, 30 , 107
(1947), J.Am.Chem.Soc., 82 , 543 (1960)] are known. However, all of these methods require the desired functional group, and they also require highly corrosive and toxic chlorine gas, hydrogen fluoride,
Sulfur tetrafluoride and antimony pentafluoride must be used, which naturally limits the range of application. Method (2) includes (a) a method of reacting iodotrifluoromethane with an aromatic compound under heating or light irradiation [for example, Chem.Pharm.Bull., 26 ;
1247 (1978)], (b) a method of reacting iodotrifluoromethane or trifluoroacetate with a halide in the presence of a metal or metal salt [e.g.
Tetrahedron Lett., 42 , 4071 (1979), Chem.
Lett., 1981 , 1679, Chem. Lett., 1981 , 1719], (c) reaction in trifluoroacetic acid under electrolytic conditions [e.g. Electrochim. Acta, 21 , 987].
(1976)], (d) Method of reacting N-trifluoromethyl-N-nitrosoarenesulfonamide with an aromatic compound or disulfide under light irradiation conditions [Tetrahedron Lett., 23 , 3929 (1982), JP-A [See No. 122344, 1982] is known. However, in method (a), the yield is low, and the trifluoromethylating agent, iodotrifluoromethane, is a gaseous substance, so pressurized conditions are required to carry out the reaction efficiently. In addition, since iodine atoms and molecules are produced, side reactions and corrosion of the reaction vessel are problematic. In method (b), in order to obtain the target product in a good yield, an expensive iodine compound must be used as a halogen compound, and since metal is used, it must be recovered according to wastewater regulations, etc. There is a problem with processing. In the method (c), special conditions of electrolytic reaction must be used, and since it is carried out in a trifluoroacetic acid solvent, the efficiency as a reagent for introducing a trifluoromethyl group is very low. In method (d), the yield is poor, and after N-trifluoromethyl-N-nitrosoarenesulfonamide acts as a trifluoromethylating agent, it becomes solid arenesulfonic acid or arenesulfinic acid, making it difficult to separate. There was a problem. The basic method for introducing a trifluoromethyl group and its drawbacks have been explained above. However, when producing β-trifluoromethylthiopropionic acid described above as a specific application of the present invention, the basic method for introducing a trifluoromethyl group is also explained. This is carried out using the conventional method described above [Tetrahedron Lett., 22 , 1997 (1981), 23 ,
3929 (1982) and Japanese Patent Application Laid-Open No. 122344/1983], and
The method found in other literature [see J.Org.Chem., 22 , 1275 (1957), U.S. Pat. It cannot be considered as an industrial production method because it requires the use of mercury salts, which causes problems with drainage, and because it involves steps with low yields. The present invention was completed as a result of extensive research to overcome the drawbacks of conventional methods. The present invention has two trifluoromethyl groups, which dramatically increases its usefulness as a trifluoromethylating agent (see Comparative Example), and since all of the decomposition products are gases, they are desirable products. It has the characteristic that trifluoromethyl compounds can be separated very easily. The N-trifluoromethyl-N-nitrosotrifluoromethanesulfonamide of the present invention can be produced by reacting trifluoronitrosomethane with hydroxylamine and then reacting it with trifluoromethanesulfonyl fluoride in the presence of a base. . Examples of bases used in this reaction include metal hydrides such as sodium hydride, potassium hydride, and lithium hydride, alkali metal alkoxides such as sodium methoxide, sodium ethoxide, and potassium t-butoxide, sodium hydroxide, and potassium hydroxide. Metal hydroxides such as the following can be used. When producing the compound of the present invention, it is desirable to carry out the reaction in a solvent, such as polar solvents such as dimethylformamide, formamide, dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide, hexamethylphosphoric triamide, etc. Ether solvents such as diethyl ether, tetrahydrofuran, etc. can be used. Moreover, a mixed solvent of these can also be used. The reaction proceeds at -100°C to -10°C, but preferably -80°C to -30°C in order for the reaction to proceed smoothly with good yield. Hereinafter, the present invention will be explained in more detail with reference to Examples, Reference Examples, and Comparative Examples. Example In a 300 ml three-neck flask under argon atmosphere, add hydroxyamine hydrochloride (5.6 g, 80.6 mmole) to dimethylformamide-diethyl ether (80 ml).
To this solution was added t-butoxypotassium (9.05 g, 80.6 mmole) under ice-cooling, and then the mixture was stirred at room temperature.
Stir for 15 minutes, cool to −62° C. to −65° C. with a dry ice-chloroform bath, and add trifluoronitrosomethane (8.3 g, 83.8 mmole) until the blue color disappears. Next, excess trifluoronitrosomethane was expelled with argon gas, and furisulfuromethanesulfonyl fluoride (12.8 g, 84.2
mmole) into the reaction system, 50% sodium hydride (4.26 g, 88.8 mmole) was added over 2 hours. After adding the entire amount and stirring at -63℃ for 18 hours, add pentane (10ml) and raise the temperature to -35℃, add water, extract with pentane, wash with water, dry with magnesium sulfate, separate and purify using a vacuum line, N- 10.0 g (50%) of trifluoromethyl-N-nitrosotrifluoromethanesulfonamide was obtained. The physical property values are shown below. Colorless volatile liquid ^19F -NMR (trichlorofluoromethane internal standard in deuterated chloroform); 69.71ppm (m, 3F,

[Formula]), 76.51 (s, 3F, CF ₃ SO ₂ −). IR (neat); 1545 cm ^-1 (N=O), 1415 (SO ₂ ). Reference example In a Pyrex reaction tube, add 3-mercaptopropionic acid (107.2 mg, 1.0 mmole) and diacetyl (88 μ, 1.0 mmole) in acetonitrile (5 ml).
Take the solution and add N-trifluoromethyl-N
- After adding nitrosotrifluoromethanesulfonamide (156 μ, 1.0 mmole), degas and seal the tube.
It was irradiated for 5 hours using a high pressure mercury lamp. The product was separated by silica gel column chromatography (pentane:ether = 4:1) and purified by vacuum distillation (125° C./12 mmHg) to obtain 157 mg (89.2%) of 3-trifluoromethylthiopropionic acid.
The physical property values are shown below. Colorless liquid ¹⁹ F-NMR (trichlorofluoromethane internal standard in deuterated chloroform); 41.5 ppm (s). ¹ H-HMR (in deuterated chloroform); 2.83 ppm (t,
2H, -CH ₂ -), 3.14 (t, 2H, -CH ₂ -), 9.13
(b, 1H, -COOH). IR (neat); 3050cm ^-1 , 1720, 1420, 1300,
1250, 1210, 1115. Comparative example N-trifluoromethyl-N- used in reference example
N-trifluoromethyl-N-nitrosobenzenesulfonamide (0.263 g, 1.04 mmole) in place of nitrosotrifluoromethanesulfonamide
The reaction was carried out using the same molar ratios and operations as in Reference Example except that . After the reaction, the reaction solution was analyzed by gas chromatography, and it was found that the production of β-trifluoromethylthiopropionic acid was 5% or less.

Claims (1)

[Claims] 1. Structural formula N-trifluoromethyl-N-nitrosotrifluoromethanesulfonamide represented by