JPH0120147B2 - - Google Patents

Description

Detailed Description of the Invention The present invention is based on the general formula RfSR ² -() (wherein, Rf is a perfluoroalkyl group having 1 to 4 carbon atoms, R ² is a carboxy group substituted, a lower alkoxycarbonyl group substituted, or a lower alkoxycarbonyl group). or a lower acylamino group substituted with a C1-C10 alkyl group, an unsubstituted C1-C10 alkyl group, or a phenyl group substituted with a lower alkyl group. Regarding. Among the perfluoroalkylthio compounds represented by the general formula () obtained by the present invention, trifluoromethylthioacetic acid and its esters are useful as modifiers for cephalosporin, etc. [THE JOURNAL OF ANTIBIOTICS, VOL.
No. 6, 463 (1975)], and β-trifluoromethylthiopropionic acid and its esters are known to be useful as plant protectants [see US Pat. No. 3,522,293]. Conventionally, methods for producing trifluoromethylthioacetic acid or its ester include (1) a method in which trifluoromethylsulfenyl silver salt obtained by reacting silver fluoride and carbon disulfide is reacted with iodoacetic acid; Zhurnal Obschchei Khimii,
35, 1628 (1965)], (2) Trifluoromethyldithioacetate obtained by reacting trifluoromethylsulfenyl chloride produced from trichloromethylsulfenyl chloride with mercaptoacetate is converted into triphenylphosphine. Method obtained by desulfurization using indium [J.Org.
Chem., 25 , 2016 (1960) and JP-A-52-144617
[J.Org.Chem., 25 , 2016 (1960) and JP-A-52-
128322], (4) Trifluoromethyldithioacetate is obtained by reacting trichloromethyldithioacetate obtained by reacting trichloromethylsulfenyl chloride with mercaptoacetate and potassium fluoride in the presence of a crown ether. and then desulfurization using triphenylphosphine [JP-A-52-144617
(5) Iodotrifluoromethane obtained from the reaction of the silver salt of trifluoroacetic acid with iodine or from the reaction of fluoroform with iodine is irradiated with mercaptoacetic acid using liquid ammonia as a solvent in a glass container. How to obtain by [J.
Chem.Soc., 1951 , 584, JP-A-52-68110 and
Zhurnal Organicheskoi Khimii, 13 , 1057
(1977)] is known. However(1)
This method cannot be said to be an economical method because it uses an expensive silver salt and requires a long time for the reaction. Methods (2), (3), and (4) use gases that are extremely toxic to raw materials, etc., and involve long steps with low yields, so they are problematic as industrial production methods. In method 5), expensive silver salts or iodine are used, and the process is complicated in that iodotrifluoromethane, which is a gas at room temperature and pressure, and highly toxic ammonia are liquefied and the photoreaction is carried out in a glass container. It is difficult to adopt this method as an industrial method because it is complicated and has safety problems.
In addition, as a method for producing β-trifluoromethylthiopropionic acid and its ester, mercuric fluoride and carbon disulfide are reacted to form trifluoromethylsulfenylmercury salt, and then treated with hydrogen chloride. As trifluoromethyl mercaptan,
A method is known in which this is then reacted with an acrylic ester under light irradiation [J.Org.Chem.,
22, 1275 (1957) and U.S. Pat. No. 3,522,293]. However, this conventional method uses highly toxic mercuric salts, produces large amounts of by-products in addition to the desired product due to the reaction between trifluoromethyl mercaptan and acrylic ester, and has problems in the manufacturing process. It cannot be said to be an economical production method because it involves long steps with low yields. As a result of repeated studies to overcome the drawbacks of conventional methods, the present inventors discovered a method for easily producing perfluoroalkylthio compounds and completed the present invention. The present invention is represented by the following reaction formula. RfNO −() [First step] ↓ RfN(NO)R −() [Second step] ↓ RfSR ² −() (wherein, Rf and R ² are the same as above, and R is a phenylsulfonyl group or a phenylsulfonyl group substituted with an alkyl group having 1 to 4 carbon atoms.) [First step] This step consists of perfluoronitrosoalkane represented by the general formula (), hydroxylamine, and the general formula RX - () (formula (wherein, R is the same as above, and X is a leaving group) to produce a perfluoroalkylnitrosamine derivative represented by the general formula (). Examples of the perfluoronitrosoalkane of the general formula () which is a raw material in this step include trifluoronitrosomethane, pentafluoronitrosoethane, heptafluoronitrosopropane, nonafluoronitrosobutane, heptafluoronitroso-i-propane, nonafluoronitrosopropane, and nonafluoronitrosoalkane. -t-
Butane etc. can be used. Further, as described above, the compound represented by the general formula () is a substituted sulfonyl compound having a leaving group. Here, the leaving group generally refers to a functional group that can be easily substituted under nucleophilic reaction conditions, and includes, for example, a halogen atom, a sulfonyloxy group, and the like. Compounds represented by the above general formula () having these groups include benzenesulfonyl chloride, benzenesulfonic anhydride, p-toluenesulfonyl chloride, p-toluenesulfonyl bromide,
Substituted sulfonyl compounds such as toluenesulfonic anhydride can be exemplified. This step is preferably carried out under basic conditions, and basic conditions include, for example, sodium methoxide,
The presence of bases such as alkali metal alkoxides such as sodium ethoxide and potassium t-butoxide, metal hydrides such as sodium hydride and calcium hydride, metal hydroxides such as sodium hydroxide and potassium hydroxide, and organic amines such as triethylamine. This can be achieved by This step is carried out by reacting the three raw materials as described above, but more preferably, after reacting the perfluoronitrosoalkane represented by the general formula () with hydroxylamine, a base is added together with RX. This is done by adding . When carrying out this step, it is desirable to use a solvent, such as alcohols such as methanol and ethanol, ethers such as diethyl ether and tetrahydrofuran (THF), dimethylformamide (DMF), and dimethyl sulfoxide (DMSO). Polar solvents can be used. The reaction proceeds at -100°C to room temperature, but in order to proceed smoothly with good yield, the reaction temperature is -80°C to -10°C.
is preferred. [Second step] This step is based on the general formula () obtained in the first step.
Perfluoroalkylnitrosamine derivatives represented by the general formula R ¹ -S-R ² -() (wherein R ¹ is a hydrogen atom, a substituted or unsubstituted alkylthio group having 1 to 10 carbon atoms, a substituted or unsubstituted alkylthio group) It is a phenylthio group, and R ² is the same as above.)
A perfluoroalkylthio compound represented by the general formula () is produced by reacting the perfluoroalkylthio compound with the thio compound represented by the above general formula (). The thio compounds represented by the general formula () include dialkyl disulfides such as dimethyl disulfide, diethyl disulfide, dibutyl disulfide, didecyl disulfide, dithiodiacetic acid and its esters, β, β Substituted dialkyl disulfides such as '-dithiodipropionic acid and its esters, γ,γ'-dithiodiacetic acid and its esters, dithiodisuccinic acid and its esters, N,N'-bis(trifluoroacetyl)homocystine dimethyl ester, 3 , 3'-bis(1-trifluoroacetylamino-1-methoxycarbonyl-3-methylbutyl) disulfide and other amino acid derivatives,
Ditolyl difluoride, bis(butylphenyl)
Diaryl disulfide such as disulfide, asymmetrically substituted disulfide such as phenylcarboxymethyl disulfide, butylcarboxymethyl disulfide, butyldecyl disulfide, phenyltolyl disulfide, β-carboxyethylcarboxymethyl disulfide, etc. , alkanethiols such as ethanethiol, butanethiol, decanethiol, mercaptoacetic acid and its esters, α-mercaptopropionic acid and its esters, β-mercaptopyropionic acid and its esters, γ-mercaptobutyric acid and its esters, mercaptosuccinic acid and substituted alkanethiols such as esters thereof,
Arylthiols such as thiocresol and butylthiophenol can be used. When carrying out this step, it is preferable to carry out the reaction in the presence of (1) light irradiation, (2) heating, or (3) a metal or its salt. In method (1), a light source generally used in the photochemical industry, such as a low-pressure or high-pressure mercury lamp or an incandescent lamp, can be used as the irradiation light source. In this case, a sensitizer is not necessarily required, but in order to shorten the reaction time and improve the yield, sensitizers such as acetophenone, benzophenone, anthraquinone, benzyl, diacetyl, pyrene, anthracene, fluorenone, etc. are commonly used in this type of reaction. A wide variety of sensitizers can be used. Method (2) can be achieved, for example, by heating the reaction system to 60°C or higher, preferably 100°C or higher. or,
Method (3) can be achieved using a catalyst that can easily perform decomposition. This catalyst is
For example, metals or metal salts of group B of the periodic table such as copper powder, copper sulfate, copper chloride, copper acetylacetone, copper acetate, silver chloride, metals or metals of group B of the periodic table such as zinc powder, zinc chloride, zinc acetate, etc. Periodic table metals or metal salts of Group B of the periodic table such as salt, manganese powder, manganese acetate, manganese chloride, iron powder, iron sulfate, acetylacetone cobalt salt, nickel powder, nickel chloride, acetylacetone nickel salt, palladium chloride, etc. Group metals or metal salts can be used. A solvent is not necessarily required to carry out this step, but if a homogeneous solution is not formed, for example, acetone, acetonitrile, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), nitromethane, acetic acid, trifluoroacetic acid. , polar solvents such as ethyl acetate, methylene chloride,
Halogenated solvents such as chloroform and tetrachloroethane, alcohols such as methanol and ethanol, ethers such as diethyl ether and tetrahydrofuran (THF), and hydrocarbon solvents such as hexane, octane and decalin can be used. Hereinafter, the present invention will be explained in more detail with reference to Examples. Example 1 (a) After 0.46 g of hydroxylamine hydrochloride was dissolved in a mixed solution of 4 ml of DMF and 1 ml of ether, 0.77 g of potassium t-butoxide was added under stirring. After 20 minutes, it was filtered to obtain a hydroxylamine solution.
After adding 5 ml of THF, the solution was cooled to −75° C., and trifluoronitrosomethane was bubbled into the solution while stirring until a blue color remained. Thereafter, a solution of 0.36 g of sodium hydride (50% in oil) and 1.27 g of benzenesulfonyl chloride dissolved in 5 ml of ether was added, and after stirring for 4 hours, the temperature was returned to room temperature. Add water;
Extracted with ether and dried over magnesium sulfate. Filtration, evaporation of the solvent, and recrystallization from pentane yielded 0.95 g of N-trifluoromethyl-
N-nitrosobenzenesulfonamide was obtained as colorless crystals. Yield 57%. The physical properties of this product were as follows. Melting point: 57-58℃. ¹⁹ F-NMR (in deuterated chloroform, CFCl ₃ internal standard): -70.5 ppm (bs, CF ₃ ). ^1H -NMR (in deuterated chloroform): 7.74ppm
(m, 3H), 8.13 (m, 2H). IR (nujol): 1510, 1450, 1360, 1310, 1260,
1160, 1130, 1080, 910, 760, 730, 600,
560cm ^-1 . Molecular weight measurement: 262 (calculated value 254). Elemental analysis: Actual value: C: 33.09, H: 1.95 N: 11.21%. Calculated value: C: 33.08, H: 1.98 N: 11.02%. (b) 78.8 mg of dithiodiacetic acid, N-trifluoromethyl-N-nitrosobenzenesulfonamide
100.6mg and benzophenone 7.5mg in acetone 1ml
After replacing with argon, the mixture was irradiated with a high-pressure mercury lamp for 5 hours. After the reaction, the solvent was distilled off, and the residue was separated and purified by gas chromatography to obtain trifluoromethylthioacetic acid. Yield 36%. The physical properties of this product were as follows. ¹⁹ F-NMR (in deuterated chloroform, CFCl ₃ internal standard): -42.4 ppm (s, CF ₃ ). ¹ H-NMR (in deuterated chloroform): δ3.70 (-
CH ₂ −). IR (neat): 3100 (broad absorption), 1725, 1420,
1390, 1110, 900, 755, 640cm ^-1 . Mass: 160 (M ⁺ ). Example 2 15.9 mg of dithiodiacetic acid, 20.3 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide and 1.1 mg of benzyl were dissolved in 0.3 ml of acetonitrile.
After replacing with argon, it was irradiated with a high-pressure mercury lamp for 4 hours. After the reaction, post-treatment was carried out in the same manner as in Example 1 (b) to obtain trifluoromethylthioacetic acid. Yield 53%. Example 3 15.7 mg of dithiodiacetic acid, 20.3 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide and 1.3 mg of acetophenone were dissolved in 0.3 ml of acetone.
After replacing with argon, it was irradiated with a high-pressure mercury lamp for 5 hours. After the reaction, post-treatment was carried out by a conventional method to obtain trifluoromethylthioacetic acid. Yield 31%. Example 4 15.7 mg of dithiodiacetic acid and 20.3 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide were dissolved in 0.3 ml of acetone, and after purging with argon, the solution was irradiated with a high-pressure mercury lamp for 7.3 hours. After the reaction, post-treatment was carried out by a conventional method to obtain trifluoromethylthioacetic acid in a yield of 35%. Example 5 44 mg of dithiodiacetic acid, N-trifluoromethyl-
20.2 mg of N-nitrosobenzenesulfonamide and 1.2 mg of benzophenone were dissolved in 0.3 ml of acetone, and after the atmosphere was replaced with argon, the mixture was irradiated with a high-pressure mercury lamp for 3.5 hours. After the reaction, post-treatment was carried out by a conventional method to obtain trifluoromethylthioacetic acid in a yield of 39% based on the sulfonamide. Example 6 16.1 mg of dithiodiacetic acid, 20.2 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide and 1.4 mg of benzophenone were dissolved in 0.3 ml of nitromethane, and after the atmosphere was replaced with argon, the solution was irradiated with a high-pressure mercury lamp for 14 hours. After the reaction, post-treatment was carried out by a conventional method to obtain trifluoromethylthioacetic acid in a yield of 19%. Example 7 16.6 mg of dithiodiacetic acid, 20.8 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide and 0.6 mg of benzophenone were dissolved in 0.3 ml of acetonitrile, and the mixture was replaced with argon and irradiated with a high-pressure mercury lamp for 3.5 hours. After the reaction, post-treatment was carried out by a conventional method to obtain trifluoromethylthioacetic acid in a yield of 41%. Example 8 16.4 mg of dithiodiacetic acid, 20.4 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide and 0.4 mg of benzophenone were dissolved in 0.3 ml of ethyl acetate, and the solution was replaced with argon and irradiated with a high-pressure mercury lamp for 5 hours. After the reaction, post-treatment was carried out by a conventional method to obtain trifluoromethylthioacetic acid in a yield of 32%. Example 9 16.7 mg of dithiodiacetic acid, 20.9 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide and 0.5 mg of benzophenone were dissolved in 0.2 ml of ethyl acetate, and after the atmosphere was replaced with argon, the solution was irradiated with a high-pressure mercury lamp for 3.5 hours. After the reaction, post-treatment was carried out by a conventional method to obtain trifluoromethylthioacetic acid in a yield of 32%. Example 10 15.9 mg of dithiodiacetic acid, 20.2 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide and 0.5 mg of pyrene were dissolved in 0.3 ml of acetonitrile, and the mixture was replaced with argon and irradiated with a high-pressure mercury lamp for 5.5 hours. After the reaction, post-treatment was carried out by a conventional method to obtain trifluoromethylthioacetic acid in a yield of 47%. Example 11 16.6 mg of dithiodiacetic acid, 20.5 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide and 0.5 mg of acetracene were dissolved in 0.3 ml of acetonitrile, and the mixture was replaced with argon and irradiated with a high-pressure mercury lamp for 3.5 hours. After the reaction, post-treatment was carried out by a conventional method to obtain trifluoromethylthioacetic acid in a yield of 40%. Example 12 15.8 mg of dithiodiacetic acid, 20.3 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide and 0.7 mg of fluorenone were dissolved in 0.3 ml of acetonitrile, and the mixture was replaced with argon and irradiated with a high-pressure mercury lamp for 3.5 hours. After the reaction, post-treatment was carried out by a conventional method to obtain trifluoromethylthioacetic acid in a yield of 38%. Example 13 16.1 mg of dithiodiacetic acid, 20.1 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide and 0.7 mg of diacetyl were dissolved in 0.3 ml of acetonitrile, and after purging with argon, the solution was irradiated with a high-pressure mercury lamp for 3.5 hours. After the reaction, post-treatment was carried out by a conventional method to obtain trifluoromethylthioacetic acid in a yield of 44%. Example 14 (a) 0.1 g of hydroxylamine hydrochloride was dissolved in 3 ml of DMF, and 0.18 g of potassium t-butoxide was added with stirring. After adding 2 ml of ether, the mixture was cooled to -70°C and trifluoronitrosomethane was blown into the solution until the blue color of the solution disappeared. Thereafter, 0.18 g of potassium t-butoxide and 0.29 g of p-toluenesulfonyl chloride were added, the reaction temperature was gradually raised to room temperature, and water was added to extract ether. After drying with magnesium sulfate, the solvent was distilled off.
The residue was separated and purified by silica gel column chromatography to obtain 0.12 g of N-trifluoromethyl-N-nitroso-p-toluenesulfonamide as colorless crystals. Yield 31%. The physical properties of this product were as follows. Melting point: 48-49℃ (recrystallized from hexane). ^19F -NMR (in deuterated chloroform, CFCl ₃ internal standard): -70.65ppm (bs, CF ₃ ). ^1H -NMR (in deuterated chloroform): 2.46ppm
(s, CH ₃ ), 7.40 (d, J=8Hz, 2H), 7.98
(d, J=8Hz, 2H). IR (nujol): 1590, 1510, 1375, 1300, 1250,
1180, 1170, 1140, 1080, 905, 810, 770,
710, 655, 595, 540 cm ^-1 . Elemental analysis: Actual values: C; 35.97, H; 2.61 N; 10.71%. Calculated value: C: 35.83, H: 2.63 N: 10.44%. (b) 14.3 mg of dithiodiacetic acid, 20.2 mg of N-trifluoromethyl-N-nitroso-p-toluenesulfonamide and 0.5 mg of benzyl were mixed with 0.3 mg of acetonitrile.
ml, and after purging with argon, it was irradiated with a high-pressure mercury lamp for 3 hours. After the reaction, post-treatment is carried out by a conventional method,
Trifluoromethylthioacetic acid was obtained with a yield of 49%. Example 15 16.5 mg of dithiodiacetic acid and 21.1 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide
After dissolving in 0.3ml of DMF, heat at 110℃ for 7 hours,
Work-up was carried out in a conventional manner to obtain trifluoromethylthioacetic acid in a yield of 3%. Example 16 16.4 mg of dithiodiacetic acid and 20.9 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide
Dissolved in 0.3ml of DMF, added 3ml of copper powder and heated to 110℃.
The mixture was heated for 15 minutes and worked up by a conventional method to obtain trifluoromethylthioacetic acid in a yield of 4%. Example 17 15.7 mg of dithiodiacetic acid and 20.3 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide were dissolved in 0.3 ml of acetonitrile, and after adding copper powder.
Heated at 75°C overnight. After the reaction, post-treatment was carried out by a conventional method to obtain trifluoromethylthioacetic acid in a yield of 4%. Example 18 18.4 mg of dimethyl dithiodiacetate, 20.0 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide, and 1.0 mg of benzophenone were dissolved in 0.3 ml of acetone, and after replacing with argon, the solution was heated with a high-pressure mercury lamp.
It was irradiated for 5.5 hours. After the reaction, post-treatment was carried out by a conventional method to obtain trifluoromethylthioacetic acid methyl ester in a yield of 36%. Example 19 A mixture of 87 mg of dimethyl dithiodiacetate and 20 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide was irradiated with a high-pressure mercury lamp for 6 hours. After the reaction, post-treatment was carried out by a conventional method to obtain trifluoromethylthioacetic acid methyl ester in a yield of 20%. Example 20 Mercaptoacetic acid n-butyl ester 32.3 mg, N
51.4 mg of -trifluoromethyl-N-nitrosobenzenesulfonamide and 4.0 mg of benzophenone were dissolved in 1 ml of acetone, 21.7 ml of sodium carbonate was added, and the mixture was irradiated with a high-pressure mercury lamp for 3 hours. After the reaction, the mixture was filtered and the solvent was distilled off. The resulting residue was filtered by silica gel column chromatography and purified to obtain trifluoromethylthioacetic acid n-butyl ester as an oil. Yield 15%. The physical properties of this product were as follows. ¹⁹ F-NMR (in deuterated chloroform, CFCl ₃ internal standard) - 42.2 ppm (s, CF ₃ ). ^1H -NMR (in deuterated chloroform): 0.94ppm (m,
3H), 1.53 (m, 4H), 3.63 (s, 2H), 4.15 (t,
6Hz, 2H). GC−Mass (m/e): 173 (M ⁺ −C ₃ H ₇ ), 143 (M ⁺
−OC ₄ H ₉ ), 115 (M ⁺ −CF ₃ S, or M ⁺ −
COOC ₄ H ₉ ). Example 21 Mercaptoacetic acid 7.7 mg, N-trifluoromethyl-N-nitrosobenzenesulfonamide 20.4 mg
and 0.7 mg of benzyl were dissolved in 0.3 ml of acetonitrile, irradiated with light using a high-pressure mercury lamp, and worked up in a conventional manner to obtain trifluoromethylthioacetic acid in a yield of 4%. Example 22 42.7 mg of α,α'-dithiodipropionic acid, 51.2 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide and 2.6 mg of benzyl were mixed with 0.75 ml of acetone.
The mixture was dissolved in water, replaced with argon, and then irradiated with light for 4.5 hours.
After the reaction, the solvent was distilled off, and the residue was isolated and purified by gas chromatography to obtain 10.9 mg of α-trifluoromethylthiopropionic acid as an oil. Yield 31
%. The physical properties of this product were as follows. ¹⁹ F-NMR (in deuterated chloroform, CFCl ₃ internal standard) - 40.5 ppm (s, CF ₃ ). ¹ H-NMR (in deuterated chloroform): 1.65 ppm (d,
8Hz, CH ₃ ), 3.95 (q, 8Hz, CH). IR (neat): 3100 (broad absorption), 1720, 1450,
1410, 1310, 1280, 1205, 1150, 1110, 750cm
^-1 . Example 23 15.7 mg of dithiodiacetic acid and 20.8 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide were dissolved in 0.3 ml of tetrachloroethane, 3 mg of acetylacetone copper salt was added, and the mixture was heated at 140°C overnight and treated in a conventional manner. Work-up to give trifluoromethylthioacetic acid in 7% yield. Example 24 16.0 mg of dithiodiacetic acid and 21.1 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide
Dissolve in 0.3ml of DMF, add 3mg of silver chloride, and heat to 110℃.
heated overnight. After the reaction, the reaction mixture was worked up by a conventional method to obtain trifluoromethylthioacetic acid in a yield of 3%. Example 25 15.7 mg of dithiodiacetic acid and 20.4 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide
Dissolve in 0.3ml of DMF and add 3mg of manganese chloride.
Heated at 110°C overnight. After the reaction, the reaction mixture was worked up in a conventional manner to obtain trifluoromethylthioacetic acid in a yield of 1%. Example 26 16.0 mg of dithiodiacetic acid and 20.4 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide
Dissolved in 0.3 ml of DMF, added 3 mg of acetylacetone cobalt () salt, heated at 110°C overnight, and post-treated in a conventional manner to dissolve trifluoromethylthioacetic acid.
% yield. Example 27 16.0 mg of dithiodiacetic acid and 22.1 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide
Dissolved in 0.3 ml of DMF, added 3 mg of acetylacetone nickel () salt, heated at 110°C overnight, and post-treated in a conventional manner to dissolve trifluoromethylthioacetic acid.
% yield. Example 28 15.7 mg of dithiodiacetic acid and 20.6 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide
The mixture was dissolved in 0.3 ml of DMF, 3 mg of iron powder was added thereto, heated at 110°C for 1 hour, and post-treated in a conventional manner to obtain trifluoromethylthioacetic acid in a yield of 1%. Example 29 15.0 mg of dithiodiacetic acid and 19.8 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide
Dissolve in 0.3ml of DMF, add zinc powder, and heat at 110℃ for 20 minutes.
The mixture was heated for 1 minute and worked up in a conventional manner to obtain trifluoromethylthioacetic acid in a yield of 1%. Example 30 15.6 mg of dithiodiacetic acid and 20.0 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide were dissolved in 0.3 ml of tetrachloroethane and heated at 140°C for 3 days. Work-up was carried out in a conventional manner to obtain trifluoromethylthioacetic acid in a yield of 11%. Example 31 42.1 mg of β,β'-dithiodipropionic acid, 50.9 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide and 2.0 mg of benzyl were added to 1.1 ml of acetone.
Dissolved in water, sprayed with argon, and then heated with a high-pressure mercury lamp.
It was irradiated for 3.5 hours. After the reaction, the solvent was distilled off, and the residue was fractionated and purified by gas chromatography to obtain β-trifluoromethylthiopropionic acid as an oil. (Yield 50%). The physical properties were as follows. ¹⁹ F-NMR (in deuterated chloroform, CFCl ₃ internal standard) - 41.7 ppm (s, CF ₃ ). ^1H -NMR (in deuterated chloroform): 2.83ppm (m,
2H), 3.14 (m, 2H). IR (neat): 3100 (broad absorption), 1720, 1420,
1110, 940, 755 cm ^-1 . Example 32 68.8 mg of di-n-decyl disulfide, 50.3 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide and 2.2 mg of benzyl were dissolved in 1.1 ml of acetone, and argon was added. After blowing, use a high-pressure mercury lamp 3
Irradiated for hours. After irradiation, the solvent was distilled off, and the residue was fractionated and purified by gas chromatography to obtain trifluoromethyl-n-decyl sulfide as an oil.
(Yield 50%). ¹⁹ F-NMR (in deuterated chloroform, CFCl ₃ internal standard) - 41.2 ppm (s, CF ₃ ). ^1H -NMR (in deuterated chloroform): 0.7-1.9ppm
(m, 19H), 2.80 (t, J=8Hz, 2H). IR (neat): 2920, 2850, 1460, 1140, 1110 cm ^-1 . Mass (m/e): 173 (M ⁺ -CF ₃ ). Example 33 47.0 mg of β,β'-dithiodipropionic acid dimethyl ester, 50.4 mg of N-trifluoromethyl-N-nitrosobenzenesulfonamide and 2.0 mg of benzyl
mg was dissolved in 0.8 mg of acetone, the mixture was replaced with argon, and then irradiated with a high-pressure mercury lamp for 4 hours. The same post-treatment as in Example 31 was carried out to obtain β-trifluoromethylthiopropionic acid methyl ester in a yield of 52%. The structure was confirmed by ¹⁹ F-, ¹ H-NMR and IR spectra. Example 34 152 mg of bis(pt-dibutylphenyl) disulfide, N-trifluoromethyl-N-nitrosobenzenesulfonamide in a Pyrex container.
118 mg of biacetyl, 10 μ of biacetyl, and 2 ml of acetone were added, and the mixture was irradiated for 3.5 hours using a 400 W high-pressure mercury lamp under an argon atmosphere. After the reaction, 1-trifluoromethylthio-4 was obtained with a yield of 35% by post-treatment in a conventional manner.
-t-butylbenzene was obtained. Its physical properties are shown below. Melting point: 96-100℃. ^1H -NMR (in deuterated chloroform): 1.33ppm (s,
3CH ₃ ), 7.25-7.6 (m, 4H). ¹⁹ F-NMR (trichlorofluoromethane internal standard in deuterated chloroform): -43.05 ppm (s, CF ₃ ). Example 35 N,N'-bis(trifluoroacetyl)homocystine dimethyl ester in a Pyrex container.
1.0g, N-trifluoromethyl-N-nitrosobenzenesulfonamide 0.56g, Biacetyl 0.19
Add 11 ml of acetone and 25 ml under argon atmosphere.
℃ and 7 hours of irradiation using a 400W high-pressure mercury lamp.
After the reaction, the solvent was distilled off and 0.38 g of N-trifluoroacetyl trifluoromethionine methyl ester (2-trifluoroacetylamino-4-trifluoromethylthio-n-methyl butyrate) was obtained as an oil by silica gel column chromatography. (yield 59%). Its physical properties are shown below. ¹ H-NMR (in deuterated chloroform) 7.1ppm (bs,
NH), 4.60 (q, J=6.5Hz, CHCO), 3.79
(S, CH ₃ ), 2.88 (t, J=7.0Hz, SCH ₂ ), 2.6
~1.9 (m, _CH2 ). ¹⁹ F-NMR (trichlorofluoromethane internal standard in deuterated chloroform): -41.4ppm (s,
CF ₃ S), -75.8 (s, CF ₃ CO). IR (neat): 3350, 1720, 1560, 1440, 1220,
1170, 1120cm ^-1 . Elemental analysis: Actual values: C: 30.52%, H: 2.85, N: 4.52%. Calculated values: C: 30.68, H: 2.90, N: 4.47%. Next, dissolve 0.35 g of the oil obtained from the above reaction in 4 ml of methanol and add a 2N aqueous sodium hydroxide solution.
1.5 ml was added and stirred at room temperature for 5 hours. Thereafter, the solvent was distilled off, a small amount of water was added, and the mixture was neutralized with dilute acid. The resulting precipitate was filtered, washed with water, washed with acetone, and dried.
0.17g trifluoromethionine (2-amino-
4-trifluoromethylthio-n-butyric acid) was obtained (yield 75%). Purification was performed by recrystallization from methanol. Next, the physical property values are shown. Melting point: 224-225°C (both decomposed) [Literature value 230°C (both decomposed)]. ¹ H-NMR (in heavy methanol) 3.59 ppm (t, J
= 6.5Hz, CHCO), 3.1 (m, SCH ₂ ), 2.2 (m,
_CH2 ). ¹⁹ F-NMR (trichlorofluoromethane internal standard in heavy methanol): -40.9 ppm (s, CF ₃ ). IR (nujol): 1590, 1510, 1100cm ^-1 . Elemental analysis: Actual values: C: 29.74, H: 3.91, N: 6.78%. Calculated values: C: 29.56, H: 3.97, N: 6.89%. Example 36 N-trifluoromethyl- in a Pyrex container
2.79 g of N-nitrosobenzenesulfonamide, 2 g of dithiodiacetic acid, 0.095 ml of diacetyl, and 22 ml of acetone were added, and after purging with argon, the mixture was irradiated for 14 hours using a high-pressure mercury lamp in a water bath at 13°C. After irradiation, fractional distillation was performed to obtain 1.1 g of trifluoromethylthioacetic acid as a pale yellow oil. Yield 63%. Boiling point: 64℃/15mmHg. Example 37 N-trifluoromethyl-
N-nitrosobenzenesulfonamide 0.73g, di-n-decyl disulfide 1g, diacetyl 0.25
ml and 12 ml of acetone were added, and the mixture was irradiated with a high-pressure mercury lamp in a water bath at 14° C. for 6 hours while blowing argon. After irradiation, acetone was distilled off and the residue was subjected to silica gel column chromatography to obtain 0.38 g of trifluoromethyl-n-decyl sulfide as a colorless liquid. Yield 55%.

Claims (1)

[Claims] 1. A general formula characterized by reacting a perfluoroalkylnitrosamine derivative represented by the general formula RfN(NO)R with a thio compound represented by the general formula R ¹ -S-R ² Method for producing a perfluoroalkylthio compound represented by RfSR ² (wherein, Rf is a perfluoroalkyl group having 1 to 4 carbon atoms, R is a phenylsulfonyl group or a phenylsulfonyl group substituted with an alkyl group having 1 to 4 carbon atoms, R ¹ is a hydrogen atom, substituted or unsubstituted carbon number 1
~10 alkylthio groups, substituted or unsubstituted phenylthio groups, and R ² is an alkyl group having 1 to 10 carbon atoms substituted with a carboxy group, a lower alkoxycarbonyl group, or a lower alkoxycarbonyl group and a lower acylamino group, or Substitution carbon number 1
~10 alkyl groups, or phenyl groups substituted with lower alkyl groups. ). 2. The method according to claim 1, which comprises carrying out the reaction under irradiation with light. 3. The method according to claim 1, which comprises carrying out the reaction under heating. 4. The method according to claim 1, which comprises carrying out the process in the presence of a metal or metal salt selected from groups b, b, b of the periodic table. 5 A perfluoronitrosoalkane represented by the general formula RfNO, hydroxylamine, and a compound represented by the general formula RX are reacted to obtain a perfluoroalkylnitrosamine derivative represented by the general formula RfN(NO)R, and then a perfluoroalkylnitrosoamine derivative represented by the general formula RfN(NO)R is obtained. A method for producing a perfluoroalkylthio compound represented by the general formula RfSR ² , characterized by reacting a thio compound represented by ¹ -S-R ² (wherein Rf is a perfluoroalkyl group having 1 to 4 carbon atoms) , R is a phenylsulfonyl group or a phenylsulfonyl group substituted with an alkyl group having 1 to 4 carbon atoms, R ¹ is a hydrogen atom, substituted or unsubstituted with 1 carbon number
~10 alkylthio groups, substituted or unsubstituted phenylthio groups, ^R2 is an alkyl group having 1 to 10 carbon atoms substituted with a carboxy group, a lower alkoxy group, or a lower alkoxycarbonyl group and a lower acylamino group, an unsubstituted carbon A phenyl group substituted with an alkyl group or a lower alkyl group of 1 to 10, and X
is a leaving group. ). 6. The method according to claim 5, which comprises reacting a perfluoronitrosoalkane, hydroxylamine, and a compound represented by the general formula RX under basic conditions. 7. The method according to claim 5, which comprises carrying out the reaction of the perfluoroalkylnitrosamine derivative and the thio compound under light irradiation. 8. The method according to claim 5, which comprises carrying out the reaction of the perfluoroalkylnitrosamine derivative and the thio compound under heating. 9 The reaction between perfluoroalkylnitrosamine derivatives and thio compounds is shown in periodic table b, b,
6. The method according to claim 5, which comprises carrying out the step in the presence of a metal or metal salt selected from group b. 10. The method according to claim 5, 6, 7, 8 or 9, wherein X is a halogen atom or a sulfonyloxy group.