RU2277532C1 - Method for preparing sulfonyl-derivatives of 3,5-diamino-1,2,4-triazole - Google Patents

Abstract

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention describes a method for preparing 5-amino-3-sulfonylamino-1,2,4-triazoles of the formula (I):

wherein R represents phenyl, para-methoxyphenyl, 2-naphthyl, para-para-toluene or para-chlorophenyl radical that can be used in manufacturing herbicides and antibacterial preparations. Method for preparing compounds of the formula (I) involves mixing 1-acetyl-3,5-diamino-1,2,4-triazole (II), pyridine and sulfonyl chloride of the formula (III):

taken in the mole ratio = (II) : (III) = 1:((0.9-1.1), and prepared mixture is heated at stirring and temperature 80-120°C followed by dilution with water, and precipitated deposit is dissolved in alkaline metal hydroxide solution at heating at temperature 90-100°C and neutralized to pH value 6-8. Method provides reducing the cost of compounds of the formula (I) based on using the less expensive raw, decreasing duration of the process and enhancing its safety.

EFFECT: improved preparing method.

2 cl, 5 ex

Description

The invention relates to the field of production of organic substances and can be used in the production of herbicides (US Patent 4,822,404, MKI C 07 D 487/04; US Patent 4,685,958, MKI C 07 D 487/04) and antibacterial compounds (Grandoni JA, Marta PT, Schloss JVJ Antimicrob. Chemother. 1998. V.42. P.475).

A known method for producing sulfonyl derivatives of 3,5-diamino-1,2,4-triazole by the interaction of dimethyl ester of cyanocarboimidodithioic acid (dimethylcyanodithioimidocarbonate) with arenesulfamides, followed by the reaction of the resulting N-cyano-N- (arylsulfonyl) -S-methylisothiozioziorazio MKI C 07 D 487/04; US Patent 4,685,958; MKI C 07 D 487/04; Kleschik WA, Dunbar JE, Snider SW, Vinogradoff AP Regiospecific Synthesis of Arenesulfonamide Derivatives of 3,5-Diamino-1,2,4-triazole // J. Org. Chem. 1988. V.53. No. 13. P.3120-3122). The disadvantage of this method is the use of expensive dimethyl ether cyanocarboimidodithioic acid and the release in the synthesis process of toxic and explosive gaseous methyl mercaptan.

A known method of producing sulfonyl derivatives of 3,5-diamino-1,2,4-triazole by the successive interaction of aryl sulfamides with carbon disulfide and iodomethane with the formation of dimethyl-N-arylsulfonyl-dithiocarboimidates, the reaction of the latter with cyanamide and the interaction of the resulting N-cyano-N- (arylsulfon -S-methylisothioureas with hydrazine (US Patent 4,822,404, MKI C 07 D 487/04; US Patent 4,685,958, MKI C 07 D 487/04; Kleschik WA, Dunbar JE, Snider SW, Vinogradoff AP Regiospecific Synthesis of Arenesulfonamide Derivatives of 3, 5-Diamino-1,2,4-triazole // J. Org. Chem. 1988. V.53. No. 13. P.3120-3122). The disadvantage of this method is the multi-stage and long duration of the process, the use of toxic and flammable carbon disulfide and iodomethane, the allocation in the synthesis of toxic and explosive gaseous methyl mercaptan.

A known method for producing sulfonyl derivatives of 3,5-diamino-1,2,4-triazole by the successive interaction of aryl sulfamides with carbon disulfide and iodomethane with the formation of dimethyl-N-arylsulfonyl dithiocarboimidates and the reaction of the latter with aminoguanidine bicarbonate in the presence of potassium hydroxide, Rajajan Ran Regiospecific Synthesis of N-Sulfonyl Derivatives of 3,5-Diamino-1-H-1,2,4-triazole and 2,5-Diamino-1,3,4-thiadiazole // Synthesis 1991. No. 3. P. 220-222). The disadvantage of this method is the use of highly toxic and flammable carbon disulfide and iodomethane, the allocation in the synthesis of toxic and explosive gaseous methyl mercaptan.

The closest to the technical result is a method for producing sulfonyl derivatives of 3,5-diamino-1,2,4-triazole by the interaction of dimethyl ether of cyanocarboimidodithioic acid (dimethylcyanodithioimidocarbonate) with arenesulfamides followed by the reaction of N-cyano-N- (arylsulfonyl-azothiobis-thiobis-bisomide) (tert-butoxycarbonylhydrazine) and cyclization of the resulting intermediates under the action of sulfuryl chloride (Chibale K., Dauvergne J., Wyatt PG A novel and Efficient Regiospecific Preparation of Arenesulfonamide Derivatives of 3,5-Diamino-1,2,4-tria zole // Synthesis 2002. No. 2. P.185-190). The disadvantage of this method is the use of expensive cyanocarboimidodithioic acid dimethyl ether and tert-butyl carbazate, toxic sulfuryl chloride, and the release of toxic and explosive gaseous methyl mercaptan and sulfur dioxide during the synthesis.

The objective of the invention is to reduce the cost of the method of producing sulfonyl derivatives of 3,5-diamino-1,2,4-triazole of the general formula (I), where R is phenyl, para-methoxyphenyl, 2-naphthyl, para-toluene, para-chlorophenyl radical, due to the use of cheaper raw materials, reducing the duration of the process, increasing the safety of the process by eliminating toxic gaseous or volatile products and reagents from the process.

The problem is achieved in that in the claimed method for producing sulfonyl derivatives of 3,5-diamino-1,2,4-triazole, 1-acetyl-3,5-diamino-1,2,4-triazole (II), pyridine and sulfonyl chloride ( III), where R has the above values, in the molar ratio (II) :( III) = 1: 0.9-1.1, and the resulting mixture is heated with stirring at a temperature of 80-120 ° C, then diluted with water, the precipitate is dissolved in water alkali metal hydroxide solution when heated to a temperature of 90-100 ° C, then the solution is neutralized to pH-6-8.

In the claimed method, instead of expensive cyanocarboimidodithioic acid dimethyl ester and tert-butyl carbazate, the readily available 1-acetyl-3,5-diamino-1,2,4-triazole (II) is used as a raw material, which can be obtained from cheap substances by the known method (Russian Patent 2148579 , MKI C 07 D 249/14). The duration of the main technological operations is reduced compared with the prototype from 38 hours to 40-60 minutes During the synthesis, toxic gaseous products (methyl mercaptan, sulfur dioxide) are not released, toxic volatile reagents (sulfuryl chloride) are not used. The temperature range of 80-120 ° C. indicated in the invention is optimal. At temperatures below 80 ° C, the process is too slow, and a rise in temperature of more than 120 ° C leads to a decrease in yield due to adverse reactions. The molar ratio (II) :( III) = 1: 0.9-1.1 is optimal, its change leads either to a decrease in the yield of the target product, or to the incomplete consumption of one of the reagents and is not economically feasible. As the alkali metal hydroxide, it is most advisable to use NaOH or KOH as the cheapest and most affordable.

The method is as follows:

1-Acetyl-3,5-diamino-1,2,4-triazole (II) is mixed with pyridine and sulfonyl chloride (III) in a molar ratio (II) :( III) = 1: 0.9-1.1 and heated with stirring and temperature 80-120 ° C until complete dissolution of the reagents (2-5 minutes). In this case, the formation of an intermediate product, 5-amino-1-acetyl-3-sulfonylamino-1,2,4-triazole, takes place. Then the mixture is diluted with water, the precipitate of the intermediate product is filtered off and dissolved in an aqueous solution of NaOH or KOH when heated to a temperature of 90-100 ° C. Heating is used to accelerate the dissolution and hydrolysis of the intermediate. Then the resulting solution is kept for 3-5 minutes and neutralized to a pH of 6-8. The precipitate of the target product is filtered off and purified by recrystallization. Get the compound of General formula (I).

Example 1

1-Acetyl-3,5-diamino-1,2,4-triazole in an amount of 14.1 g (0.1 mol) is mixed with 50 ml of pyridine and 19.1 g (0.1 mol) of para-toluenesulfonyl chloride. The mixture is heated with stirring to a temperature of 110-115 ° C until the reagents are completely dissolved (3 min), then diluted with 100 ml of water. The precipitate formed is filtered off and dissolved by heating in a solution of 5.4 g of NaOH in 60 ml of water. The resulting solution is maintained at 90-100 ° C for 3-5 minutes, then neutralized with acetic acid to a pH of 6-8. The precipitate formed is filtered off, washed with water and 15.2 g (60%) of 5-amino-3-para-toluenesulfonylamino-1,2,4-triazole are obtained. _Mp 314-315 ° C (from DMF - ethanol 1: 2).

¹ H NMR spectrum, δ, ppm (DMSO-d ₆ ): 2.35 s (3H, CH ₃ ), 5.65 s (2H, NH ₂ ), 7.23 d (2H, arom., J = 8.0), 7.66 d (2H, arom., J = 8.0) 11.27 s (1H, NH); 11.64 s (1H, NH).

Found (%): C, 42.4; H, 4.1; N, 27.4; S, 12.2.

C ₉ H ₁₁ N ₅ O ₂ S

Calculated (%): C, 42.7; H, 4.4; N, 27.7; S, 12.7.

Example 2

1-Acetyl-3,5-diamino-1,2,4-triazole in an amount of 14.1 g (0.1 mol) is mixed with 50 ml of pyridine and 19 g (0.09 mol) of para-chlorobenzenesulfonyl chloride. The mixture is heated with stirring at a temperature of 80-100 ° C until the reagents are completely dissolved (5 min), then diluted with 100 ml of water. The precipitate formed is filtered off and dissolved by heating in a solution of 5.4 g of NaOH in 60 ml of water. The resulting solution is maintained at 90-100 ° C for 3-5 minutes, then neutralized with acetic acid to a pH of 6-8. The precipitate formed is filtered off, washed with water and 12.7 g (49%) of 5-omino-3-para-chlorobenzenesulfonylamino-1,2,4-triazole are obtained. _Mp 305-306 ° C (from DMF - ethanol 1: 2).

¹ H NMR spectrum, δ, ppm (DMSO-d _6): 5.86 s (2H, NH _2), 7.57 d (2H, aromatic, J = 8.5.), 7.78 d (2H, aromatic, J = 8.5.), 11.58 s (1H, NH), 11.94 s (1H, NH).

Found (%): C, 35.3; H, 2.8; N, 25.6; Cl, 13.0; S, 11.2.

C ₈ H ₈ ClN ₅ O ₂ S

Calculated (%): C, 35.1; H, 2.95; N, 25.6; Cl, 12.95; S, 11.7.

Example 3

1-Acetyl-3,5-diamino-1,2,4-triazole in an amount of 14.1 g (0.1 mol) is mixed with 50 ml of pyridine and 19.4 g (0.11 mol) of benzenesulfonyl chloride. The mixture is heated with stirring at a temperature of 110-115 ° C until the reagents are completely dissolved, then diluted with 100 ml of water. The precipitate formed is filtered off and dissolved by heating in a solution of 5.4 g of NaOH in 60 ml of water. The resulting solution is maintained at 90-100 ° C for 3-5 minutes, then neutralized with acetic acid to a pH of 6-8. The precipitate formed is filtered off, washed with water and 9.6 g (40%) of 5-amino-3-benzenesulfonylamino-1,2,4-triazole are obtained. _Mp 293-294 ° C (from DMF - ethanol 1: 2).

¹ H NMR spectrum, δ, ppm (DMSO-d ₆ ): 5.83 s (2H, NH ₂ ), 7.49-7.79 m (5H, arom.), 11.48 s (1H, NH), 11.87 s (1H, NH).

Found (%): C, 40.4; H, 4.0; N, 29.4.

C ₈ H ₉ N ₅ O ₂ S

Calculated (%): C, 40.2; H, 3.8; N, 29.3.

Example 4

1-Acetyl-3,5-diamino-1,2,4-triazole in an amount of 14.1 g (0.1 mol) is mixed with 50 ml of pyridine and 20.4 g (0.09 mol) of naphthalene-2-sulfonyl chloride. The mixture is heated with stirring at a temperature of 80-100 ° C until the reagents are completely dissolved, then diluted with 100 ml of water. The precipitate formed is filtered off and dissolved by heating in a solution of 5.4 g of NaOH in 60 ml of water. The resulting solution is maintained at 90-100 ° C for 3-5 minutes, then neutralized with acetic acid to a pH of 6-8. The precipitate formed is filtered off, washed with water and 21.4 g (82%) of 5-amino-3-naphthalene-2-sulfonylamino-1,2,4-triazole are obtained. _Mp 305-308 ° C (from DMF - ethanol 1: 2).

¹ H NMR spectrum, δ, ppm (DMSO-d _6): 5.85 s (2H, NH _2), 7.58-8.05 m (6H, arom.), 8.42 s (1H, arom.), 11.55 s (1H, NH), 11.88 s (1H, NH )

Found (%): C, 49.5; H, 3.8; N, 24.5.

C ₁₂ H ₁₁ N ₅ O ₂ S

Calculated (%): C, 49.8; H, 3.8; N, 24.2.

Example 5

1-Acetyl-3,5-diamino-1,2,4-triazole in an amount of 14.1 g (0.1 mol) is mixed with 50 ml of pyridine and 22.7 g (0.11 mol) of para-methoxybenzenesulfonyl chloride. The mixture is heated with stirring at a temperature of 110-115 ° C until the reagents are completely dissolved (5 min), then diluted with 100 ml of water. The precipitate formed is filtered off and dissolved by heating in a solution of 5.4 g of NaOH in 60 ml of water. The resulting solution is maintained at 90-100 ° C for 3-5 minutes, then neutralized with acetic acid to a pH of 6-8. The precipitate formed is filtered off, washed with water and 17.5 g (65%) of 5-amino-3-para-methoxybenzenesulfonylamino-1,2,4-triazole are obtained. _Mp 293-294 ° C (from DMF - ethanol 1: 2).

¹ H NMR spectrum, δ, ppm (DMSO-d ₆ ): 3.90 s (3H, OCH ₃ ), 5.84 s (2H, NH ₂ ), 6.96 d (2H, arom., J = 9.0), 7.82 d (2H, arom., J = 9.0) 11.57 s (1H, NH); 11.93 s (1H, NH).

Found (%): C, 39.7; H, 4.1; N, 25.9; S, 12.0.

C ₉ H ₁₁ N ₅ O ₃ S

Calculated (%): C, 40.1; H, 4.1; N, 26.0; S, 11.9.

Claims (1)

The method of obtaining sulfonyl derivatives of 3,5-diamino-1,2,4-triazole of General formula (I),

where R is phenyl, para-methoxyphenyl, 2-naphthyl, para-toluene, para-chlorophenyl radical, characterized in that 1-acetyl-3,5-diamino-1,2,4-triazole (II) is mixed,

pyridine and sulfonyl chloride (III),

where R has the above meanings, in the molar ratio (II) :( III) = 1: 0.9-1.1, and the resulting mixture is heated with stirring at a temperature of 80-120 ° C, then diluted with water, the precipitate formed is dissolved in an aqueous solution of alkali metal hydroxide when heated to a temperature of 90- 100 ° C, then the solution is neutralized to a pH of 6-8.