DE1168896B - Process for the preparation of N, N-disubstituted amidines - Google Patents

Description

Process for the preparation of N, N-disubstituted amidines Process for the preparation of N, N-disubstituted amidines are already known. So get the compounds of nitriles and N, N-disubstituted aminomagnesium halides after E. Lo r z and R. B alt zly, J. Am. Soc., 70, p. 1904 (1948), and R. P. Hullin, J. Miller and W. F.

Shor t, J. Chem. Soc., 1947, p. 394. This method has the disadvantage that the amino magnesium halides are difficult to access. According to a different procedure are nitriles with secondary amines in the presence of aluminum chloride at higher Temperatures implemented (P.Oxley, M.W.Partridge and W. F. Short, J. Chem. Soc., 1947, P. 1110); this process is accompanied by disruptive side reactions. In the end are N, N-disubstituted amidines also according to the method of P i n n e r, »Die iminoäther and their derivatives ", 5. 86 off., Verlag R. Oppenheim, Berlin, 1892, through implementation the imidoesters with secondary amines, which are also not easily accessible, are available.

It has now been found that N, N-disubstituted amidines of the general formula 1 in which R1, R2 and R3 - can be alkyl, cycloalkyl or aryl radicals optionally substituted by low molecular weight alkyl groups and R3 can additionally stand for hydrogen or in which R1 can be linked to R2 or to R3 in a ring, if N, N- disubstituted N'-halosulfonylamidines of the general formula II in which R1, R2 and R3 have the meanings given above and X is chlorine or bromine, subjected to solvolysis by means of water or alcohols, preferably those having up to 4 carbon atoms.

The resulting N, N-disubstituted amidine salts can be used as such isolated or converted into the free amidines by means of bases.

Particularly suitable starting materials for the present process are z. B. the following N, N-disubstituted N'-halosulfonylamidines: N, N-dimethylformamidine - N '- sulfohalide, N, N - dimethylazetamidine - N' - sulfohalide, N, N - diphenylformamidine-N'-sulfohalide, N-methyl-N-phenylazetamidine-N'-sulfohalide, N, N-dimethylbenzamidine-N'-sulfohalide, I-methyl-2-chlorosulfonylimino-pyrrolidine, 1-methyl -2-chlorosulfonyliminoaza - cycloheptane, 1,4,4 - trimethyl - 2 - chlorosulfonylimine bazetidine, 1,3,3,4,4 pentamethyl-2-chlorosulfonylimino - azetidine, N - pentamethylene - azetamidine-N '- sulfohalide, N - morpholino - acetamidine-N'-sulfohalide.

These starting materials can be made according to the method of the German patent 1144 718.

The solvolysis of the N, N-disubstituted N'-halosulfonylamidines can be carried out in two embodiments, as the following equation shows, in which R is a hydrocarbon radical. preferably with 1 to 4 carbon atoms: The solvolysis takes place on the one hand in the presence of water at temperatures between 0 and 100 ° C., preferably between 20 and 60 ° C. With the sulfuric acid and hydrohalic acid formed during the hydrolysis, stable amidine salts are formed, which are converted into the free amidines by treatment with alkaline agents Defined salts of the amidines obtained by the present process can also be prepared by precipitating either the hydrohalic acid or the sulfuric acid by customary methods, for example by adding silver nitrate or barium sulfate.

Solvolysis with alcohols can be carried out at the level of the amidine-N'-sulfonic acid interrupt when working at temperatures below 40 ° C. At higher temperatures, preferably at 40 to 60 ° C., alcoholysis of the amidine-N'-sulfonic acid to amidine alkyl sulfate takes place. These salts can be obtained in great purity and with good yield.

In contrast to known methods of producing amidines it is preserved one by the method according to the invention in a gentle manner completely uniform Products. This procedure is particularly beneficial because it allows you to get out easily accessible starting materials the N, N-disubstituted amidines with low energy consumption and to produce in good to very good yields while avoiding side reactions.

In particular, according to the present process, from the amidine-N'-sulfohalides semicyclic four-membered, ring-shaped amidines are obtained from four-ring lactams, which represent a previously unknown class of compounds.

The N, N-disubstituted ones made by the present process Amidines or their salts are valuable intermediate products for the synthesis of medicinal products, Pesticides, corrosion inhibitors and antioxidants.

Example 1 I -Methyl-2-imino-pyrrolidine a) Preparation of the starting material: 1 -Methyl-2-chlorosulfonylimino-pyrrolidine For the solution of 141.5 g of chlorosulfonyl isocyanate (1 mol) in 500 ml of anhydrous ether is added dropwise at -200C and with stirring 99.1 g 1-methylpyrrolidone- (2) (1 mole). The mixture is allowed to reach room temperature, with I mole of carbon dioxide escapes. The crystal suspension that has formed will Aspirated, washed with ether and dried. 189.8 g are obtained, almost colorless Crystals with a melting point of 78 to 80 "C. The yield is 97% of theory. B) 1-methyl-2-iminopyrrolidine hydrochloride 196 g of the sulfochloride prepared as above (1 mol) are added to 500 ml of water. To complete the immediately starting After the self-heating has subsided, hydrolysis is refluxed for 5 minutes. then added a solution of 256 g of barium acetate (1 mol) in 250 ml of water and sucks off the barium sulfate. The filtrate is brought to dryness in vacuo and the Recrystallized residue from alcohol. 98.6 g of 1-methyl-2-imino-pyrrolidine hydrochloride are obtained in colorless crystals with a melting point of 186 to 187 ° C. (73% of theory).

Analysis: C5H11N2Cl (134.6).

Calculated ..... N 20.8, Cl 26.3 / o; found ..... N 20.7, Cl 26.4%. c) 1-methyl-2-iminopyrrolidine 98.6 g as hydrochloride prepared under b) (0.73 Mol) is dissolved in 250 ml of methanol to the solution of 18.5 g of sodium (0.8 mol) in 250 ml Methanol. One sucks off the table salt and submits that Fractional distillation filtrate. 62.4 g (820/0 of theory) of 1-methyl-2-iminopyrrolidine are obtained with a boiling point of 77 "C at 20 mm Hg with a refractive index of n = 1.4959.

Analysis: C5H10N2 (98.15).

Calculated ..... N 28.50 / 0; found ..... N 28.4 ° / o.

Example 2 1,4,4-trimethyl-2-imino-azetidine a) Preparation of the starting material: 1,4-trimethyl-2-chlorosulfonylimino-azetidine. The solution is left to a solution of 283 g of chlorosulfonyl isocyanate (2 mol) in 1000 ml of anhydrous ether while stirring and cooling to -10 ° C of 226 g (2 mol) of 1,4,4-trimethyl-azetidinone- (2) in 250 ml of ether. When the evolution of carbon dioxide has ceased, the crystalline reaction product is filtered off with suction, washed with ether and dried. 400 g of 1,4 are obtained. 4-Trimethyl-2-chlorosulfonylimino-azetidine (950/0 of theory) as slightly yellowish crystals. The substance can be purified by dissolving in chloroform and precipitating with carbon tetrachloride. The melting point is then 162 "C. The raw product is also suitable for further processing. b) 1,4-trimethyl-2-imino-azetidine hydrochloride 420 g of the sulfochloride prepared as above are heated to boiling in 2000 ml of water for 15 minutes and in this solution 630 g of barium hydroxide (octahydrate) (2 mol) registered.

It is boiled for a few more minutes, then the barium sulphate is suctioned off and steamed the filtrate to dryness in vacuo and the residue crystallizes from isopropanol around. 258 g of 1,4,4-trimethyl-2-imino-azetidine hydrochloride are obtained as colorless Crystals with a melting point of 190 to 191 ° C (840/0 of theory).

Analysis: C6H13N2Cl (148.6).

Calculated ... C 48.5, H 8.8, N 18.9, C 123.90 / 0; found .. C 48.4, H 8.8, N 18.6, Cl 24.00 / 0. c) 1,4,4-Trimethyl-2-imino-azetidine a) From the hydrochloride (b) 100 g of the amidine hydrochloride described under b) (0.67 mol) are under 300 ml of ether are shaken with 100 g of 500% sodium hydroxide solution until the salt dissolves. After decanting the ether, extract four more times with ether and dry the combined ether layers over NaOH, the ether is distilled off and rectified the residue in vacuo. 69.3 g (920/0 of theory) of 1,4,4-trimethyl-2-imino-azetidine are obtained with a boiling point of 70 "C at 20 mm Hg with a refractive index of n2Do = 1.4654.

Analysis: C6H12N2 (112.2).

Calculated ..... N 25.00 / 0; found ..... N 25.00 / 0. d) 1,4,4-trimethyl-2-imino-azetidine-methyls 52.5 g of the sulfochloride mentioned under a) (0.25 mol) are dissolved in 150 ml of methanol heated to 40 ° C. until the evolution of methyl chloride has ended and the crystallization the 1,4,4-trimethyl-2-imino-azetidine-N-sulfonic acid does not increase any further.

This sulfonic acid (melting point 228 "C) is obtained by briefly heating the Mixture converted to 40 to 60 "C in the amidine methyl sulfate, whereby the Dissolve crystals. After evaporation in vacuo and recrystallization of the residue 35.6 g of 1,4,4-trimethyl-2-imino-azetidine methyl sulfate are obtained from ethyl acetate-methanol in colorless crystals with a melting point of 130 to 131 ° C. (640/0 of theory).

Analysis: C7H16N204S (224.3).

Calculated ... C 37.5, H 7.2, N 12.5, S 14.30 / 0; found ... C 37.8, H 7.3, N 12.5, S 14.20 / 0. e) 22.4 g of 1,4,4-trimethyl-2-imino-azetidine methyl sulfate (0.1 mol) are mixed under 150 ml of ether with a solution of 4.1 g of NaOH in 15 ml of water Shaken until the salt dissolves. After decanting the ethereal layer, extracted three times with ether, the combined ether phases dried over NaOH and after evaporation of the ether, the residue is distilled in vacuo. 6.5 g are obtained (580/0 of theory) 1,4,4-trimethyl-2-imino-azetidine with a boiling point of 90 "C at 20 mm Hg with a refractive index of n2D = 1.4654.

Example 3 1,3,3,4,4-pentamethyl-2-imino-azetidine a) Preparation of the starting material: 1,3,3,4,4-pentamethyl-2-chlorosulfonylimino-azetidine 14.1 g of 1,3,3,4,4-pentamethyl-azetidinone (0.10 mol) are in 100 ml A solution of 14.1 g of chlorosulfonyl isocyanate (0.10 mol) in 20 ml of hexane is added to n-hexane at 20 ° C. with stirring 21.5 g of 1,3,3,4,4-pentamethyl-2-chlorosulfonylimino-azetidine of melting point 73 to 74 ° C. (900/0 of theory) are obtained. b) 1,3,3,4,4-pentamethyl-2-imino-azetidine hydrochloride 21.8 g of the sulfochloride prepared as above (0.091 mol) are boiled in water for 15 minutes, the mixture with 28.8 g of barium hydroxide octahydrate ( 0.091 mol) proportionally added and the barium sulfate filtered while still hot. The filtrate is brought to dryness in vacuo and the residue is recrystallized from isopropanol ether. 12.3 g of 1,3,3,4,4-pentamethyl-2-imino-azetidine hydrochloride (76.50 / 0 of theory) with a melting point of 205 to 206 ° C. are obtained.

Analysis: C8H17N2C1 (176.7).

Calculated ... C 54.4, H 9.7, N 15.9, Cl 20.1%: found ... C 54.1, H 9.7, N 16.3, Cl 19.80ill.

Example 4 N-Methyl-N-phenyl-acetamidine a) Preparation of the starting material: N-methyl-N-phenyl-acetamidine-N'-sulfochloride 71.5 g of N-chlorosulfonyl isocyanate (0.5 mol) are dissolved in 70 ml of anhydrous isopropyl ether and stirred at 0 ° C. 74 , 5 g of N-methylazetanilide (0.5 mol) dissolved in 200 ml of anhydrous methylene chloride were added dropwise. Carbon dioxide escapes and the N-methyl-N-phenyl-acetamidine-N'-sulfochloride separates out in colorless crystals. The mixture is stirred for a further 30 minutes at 25 ° C. in order to complete the elimination of CO2; the reaction mixture is then cooled to -20 ° C. and the sulfochloride is filtered off with suction.

110 g of N-methyl-N-phenyl-acetamidine-N'-sulfochloride (890/0 of theory) with a melting point of 126 ° C. are obtained. b) N-methyl-N-phenyl-acetamidine hydrochloride 123 g (0.5 mol) of the sulfochloride obtained as above are refluxed with 250 ml of water for 30 minutes. An aqueous solution of 122 g of barium chloride (2 H2O) is then added and the barium sulfate which has separated out is filtered off while hot.

The filtrate is concentrated to dryness in vacuo with absolute methanol taken up, filtered off from a little undissolved material and the filtrate was mixed with ether. The N-methyl-N-phenyl-acetamidine hydrochloride separates into colorless leaflets away. 70 g of N-methyl-N-phenyl-acetamidine hydrochloride (820/0 of theory) are obtained with a melting point of 250 ° C.

Analysis: CsH13NCI (184.7).

Calculated .. .. Cl 19.20 / 0; found .. .. Cl 19.10 / 0.

Example 5 N, N-Dimethylformamidine a) Preparation of the starting material: N, N-Dimethylformamidine-N'-sulfochloride 71.5 g of N-chlorosulfonyl isocyanate (0.5 mol) are dissolved in 70 ml of absolute diethyl ether and 36.5 g of a solution of dimethylformamide (0.5 mol) in 30 ml of anhydrous diethyl ether are added dropwise at 0 ° C. with stirring. After the dropwise addition, stirring is continued for 1 hour at 30.degree. C. in order to end the elimination of CO2, and the ether is then distilled off in vacuo. 86 g of N, N-dimethylformamidine-N'-sulfochloride are obtained as a pale yellow oil. b) N, N-dimethylformamidine hydrochloride 86 g (0.5 mol) of the sulfochloride prepared according to a) are introduced into 100 ml of water. To complete the hydrolysis, which starts immediately, the mixture is refluxed for 30 minutes, the aqueous solution of 122 g of barium chloride 2 H 2 O is added and the barium sulfate is filtered off with suction. The filtrate is concentrated to dryness in vacuo, taken up in absolute methanol and a little undissolved material is filtered off. The filtrate is concentrated in vacuo until crystallization begins and the crystallization is completed by cooling. 36.5 g of N, N-dimethylformamidine hydrochloride are obtained as colorless crystals (680 per cent of theory) with a melting point of 189 to 1910.degree.

Analysis: C3H9N2Cl (108.6).

Calculated . . . . Cl 32.80 / o; found .. . Cl 32; 6 ° ln.

Claims (1)

Claim: Process for the preparation of N, N-disubstituted amidines of the general formula 1 and their salts, in which R1, R2 and R3 - optionally substituted by low molecular weight alkyl groups - denote alkyl, cycloalkyl or aryl radicals and R3 can additionally be hydrogen, or in which R1 is linked to R2 or to R3 in a ring, characterized in that one N, N4isubstituted N-halosulfonylamidines of the general formula II where R1, Ri and R3 have the meanings given above and X stands for chlorine or bromine, subjected to solvolysis by means of water or alcohols, preferably with those of up to 4 carbon atoms, and optionally converted into the free amidines by means of a base.