The way to obtain secondary amines

 

(57) Abstract:

The invention relates to organic chemistry, particularly to a process for the preparation of secondary amines from the corresponding sulfonamides. Secondary amines are used in organic synthesis, production of biologically active substances, medicinal preparations, as well as analytical reagents and chelating agents. The invention solves the problem of simplifying the flow conditions of hydrolysis, reduction in reaction time, reducing the amount of acid, to increase the yield and purity of the target product is a secondary amine. This object is achieved due to the fact that N,N-disubstituted sulfonamides subjected to hydrolysis 20-30% sulfuric acid in a Teflon autoclave under the influence of the microwave field power 350 W for 0.5 hours

The invention relates to organic chemistry, particularly to a process for the preparation of secondary amines from the corresponding sulfonamides. Secondary amines are used in organic synthesis, production of biologically active substances, medicinal preparations, as well as analytical reagents and chelating agents.

One of the widely used methods for the synthesis of secondary amines is the alkylation of mono-N-Sniezka syntheses, part 1, M.: Mir, 1973, S. 5011]. Very often, this method is used in the synthesis polyazamacrocycles connections Richman-Atkins.

A method of obtaining secondary amine of N,N-disubstituted p-toluensulfonate by hydrolysis with concentrated sulfuric acid at 100oC [H. Stetter, Chem.Ber., 1953, B. 96, No. 2, S. 197-205], and a solution of HBr in acetic acid at 100oC [R. C. Fuson, H. O. House, J. Am.Chem.Soc., 1953, v.75, No. 22, p. 5744].

The disadvantages of these methods are long (70 - 100 h) heated to 100oC in concentrated acids and the need to process large volumes of highly acidic solutions when selecting substances.

Closest to the described method according to the technical essence and the achieved result is a method of obtaining secondary amines of sulfonamides by hydrolysis sulfa communication in concentrated sulfuric acid, the process is conducted at 100oC for 70 - 100 h, the output is 50 - 80% [E. J. Richman and T. J. Atkins, J. Am.Chem.Soc., 1974, 96, 2268].

The disadvantages of this method are strict conditions of synthesis, which leads to the partial destruction of the parent compounds and the lowering of the outputs of the reaction products, and the need of 0.8 - 1.0 l of 97% sulfuric acid at each toiley group hatshepsuts and other protective group, for example benzyl.

The invention solves the problem of simplifying the flow conditions of hydrolysis, reduction in reaction time, reducing the amount of acid, to increase the yield and purity of the target product is a secondary amine.

This object is achieved due to the fact that N,N-disubstituted sulfonamides is subjected to hydrolysis of 20 to 30% sulfuric acid in a Teflon autoclave under the influence of the microwave field power 350 W for 0.5 h

The essence of the proposed method is to carry out hydrolytic cleavage sulfa connection with the use of 20-30%-aqueous solution of sulfuric acid in a microwave field with a capacity of 350 W for 0.5 h

The concentration of acid used may vary in the range from 20 to 30%. The yield of the target product increases with increasing acid concentration from 20 to 25%, and then decreases with further increase in concentration from 25% to 30%.

This method allows to increase the purity and yield of secondary amines by the hydrolysis of the corresponding N,N-disubstituted p-toluensulfonate to 95%.

The following examples illustrate the proposal.

Example 1. 0.5 g of N-Oilpipeline and 5 ml of 20% aqueous solution of sulfuric and radiation 350 watts. In the resulting solution is added a 40% solution of NaOH to pH 12 and the hydrolysis product is distilled off with steam. From the distillation piperidine isolated in the form of picrate. 400 mg (60%), so pl. of picrate 152oC.

Example 2. Similar to the above using 5 ml of 25% aqueous solution of sulfuric acid. Receive 665 mg picrate piperidine, so pl. 152oC, quantitative.

Example 3. Analogously to example 1 using 5 ml of 30% sulfuric acid. Receive 400 mg of picrate piperidine, yield 60%, so pl. 152oC.

Example 4. 1.0 g (1,75 mmol) 1,10-Detail-1,10-diaza-4, 7, 13, 16-tetrachloroethane and 5 ml of 25% aqueous solution of sulfuric acid was placed in a Teflon autoclave microwave ovens MDS-2000 and incubated for 0.5 h at a power of 350 watts. To the resulting solution add 20% solution of NaOH to reach pH 10. Then the solution is extracted with CHCl35 2 ml), dried over Na2SO4and the solvent evaporated. After recrystallization from a mixture of benzene with heptane receive 436 mg of pure 1,10-diaza-18-crown-6, so pl. 115oC.

Example 5. 1.0 g (1,27 µm) 1, 4, 7, 10-Tetramethyl-1,4,7,10-tetraazacyclododecane and 5 ml of 25% aqueous solution of sulfuric acid was placed in a Teflon autoclave microwave ovens MDS-2000 and withstand actor extracted with CHCl3(5 x 2 ml), dried over NaSO4and the solvent evaporated. After recrystallization from heptane obtain 197 mg 1, 4, 7, 10-tetraazacyclododecane, so pl. 111 - 112oC.

Example 6. 1.0 g (1.38 mmol) of 1-Benzyl-4, 7, 10-Tritonal-1,4,7,10-tetraazacyclododecane and 5 ml of 25% aqueous solution of sulfuric acid was placed in a Teflon autoclave microwave ovens MDS-2000 and incubated for 0.5 h at a power of 350 watts. To the resulting solution add 20% solution of NaOH to reach pH 10. Then the solution is extracted with CHCl3(5 x 2 ml), dried over Na2SO4and the solvent evaporated. Obtain 289 mg of 1-benzyl-1,4,7,10-tetraazacyclododecane in the form of a colorless oil. Range1H NMR ([2H2] water, HCl , ppm): 3,2 (16 H, m, 8 CH2), 4,1 (2H, s, CH2Ph), and 7.3 (5H, c, C6H5). m/e 263 (M + 1)+.

Example 7. Analogously to example 6 using 0.5 g (is 1.81 mmol) of N-methyl-N-tosyl-1,2-phenylenediamine and 5 ml of 25% aqueous solution of sulfuric acid. Obtain 215 mg of N-methyl-1,2-phenylenediamine, so Kip. 123o/10 mm RT.article The output is 97%.

Example 8. 0.9 g (1.6 mmol) of 1,4,7-Triethyltetramine and 5 ml of 25% aqueous solution of sulfuric chilcote placed in a Teflon atolaw mikrovolnovaya furnace MDS-2000 and incubated for 0.5 h at a power of 350 watts. The solution was diluted with ditelindjen in the form of a colorless oil, yield 91%.

The proposed method allows to obtain heterocyclic and aromatic secondary amines in high yield and purity, as well as in a shorter time with fewer acid, which is confirmed by the examples.

The way to obtain secondary amines by hydrolysis of N,N-disubstituted p-toluensulfonate, characterized in that the hydrolysis lead to 20-30% sulfuric acid under the influence of the microwave field.

 

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