DE870552C - Process for the preparation of new amidine salts - Google Patents

Description

Process for the preparation of new amidine salts It has been found that salts of the general formula where R1 is a straight or branched alkyl radical with at least 2 carbon atoms, X is an oxygen or sulfur atom, an NH group or a methylene radical which may also contain alkyl radicals, and where R2 is the anion of an aromatic amino, oxy or diamino , Dioxy-, amino-oxycarboxylic or -sulphonic acid means, have excellent bactericstatic properties. They act partly on tubercle bacilli, partly also on gram-negative and -positive cocci and inhibit development. Many of these salts are sparingly soluble in water, so that they can only be used orally, others again show very good solubility in water, usually with a neutral reaction, so that they can easily be injected.

The salts of p-aminosalicylic acid have proven to be particularly effective, the p aminobenzoic acid, partly also that of the sulfanilic acid and the p-oxy-and o-Oxybenzoic acid proved. That p-aminosalicylic acid salts against tubercle bacilli could be effective, it could not be expected on the basis of the previously known literature but that they inhibit the development of gram-positive and gram-negative cocci. Even the salicylates and p-oxybenzoates are effective against both types of cocci.

The salts in question can be prepared in a manner known per se are, for example, through conversion of amidines, guanidines or Alkyl iso- (thio) ureas with the corresponding acids in a solvent or in water. On the other hand you can also use inorganic acid salts of amidines, etc. with base salts of the desired React acids. The choice of solvent or diluent will depend on the specific solution relationships to be implemented and of the formed salt pairs have to judge. Examples i. iogTri-n-butylacetamidine and 6.84gp-aminosalicylic acid are dissolved in zoo cc of ethanol, the solution is filtered, at low temperature evaporated and the residue rubbed with 50 cc ether. sMan sucks the educated Salt off; -Dissolve it in 50 cc of acetone and add 10,000 cc of ligroin. One obtains @ III, 7 g of pure tri-n-butylacetami.diniump-aminosalicylate, which is present in the range from 78 to 179 ° melts. The new salt is insoluble in water and ligroin, in acetone, ethanol, . Easily soluble methanol, dioxane, ethyl acetate and chloroform.

2. iv g lauramidine chlorohydrate and s7.5. g of sodium p-aminosalicylate are mixed in 66 ccm of 50% ethanol. A clear solution is created immediately. After 10 minutes the lauramidinium p-aminosalicylate begins to separate out in star-shaped crystals. You let it stand at io` ° for the day, then sucks off the salt and dries it. By reprecipitating from acetone-ligroin, the new salt is obtained in beautiful, colorless crystals that melt at -13o to I32 °. The final weight is 9 g, which corresponds to a yield of 6o0 / 9. The new salt dissolves very easily in ethanol, methanol, chloroform and acetone, but little in water and dioxane.

3. 5 g of dodecylguanidine bromohydrate and 2.84 g of sodium p-aminosalicylate are mixed with one another in 35 cc of 75% ethanol. sMan. steams. to dryness, the residue is taken up in 70 cc of ethanol, filtered and mixed with 100 cc of water. After 2 days, 5 g of the nicely crystallizing dodecylguanidinium salt of p-aminosalicylic acid, melting at 69 to 7%, is obtained. This can be recrystallized from chloroform and petroleum ether and then melts at 75 to 76 ° @.

4. 5 g of 2,2,2-tributylaphylguanidine in 100 cc of ethanol and 3 g of p-aminosalicylic acid in 10 o cc of 75% ethanol were mixed, the solution filtered, and the whole thing evaporated to dryness. The residue is made from ethanol by careful addition dropped by water. This gives 4 to 5 g of 2, z-tributylethylguanidine-p-aminosalicylate, that melts at 15o to 1.51 ° and in water little, in methanol, ethanol and acetone is easily soluble.

. The following can be prepared in the same way: the p-aminosalicylates, the p-aminobenzoates, the sulfanilates, the salicylates and the gentisoates of triethylacetamidine, Tripropylacetamidine, n-decylguanidine, n - undecylguanidine, hexylguanidine, n-cetylguanidine, Terdecylguanidine, O-isopropylisourea, O-n-butylisoleurea, O'-n-hexylisourea, O-n-octylisourea, O-n-decylisourea, O-n-undecylisourea, O-n-dodecylisourea, -O-n-cetylisourea, S-n-butylisothiourea, S-n-decylisothideurea, S-n-cetylisothiourea.

Claims (1)

PATENT CLAIM: Process for the preparation of new amidine salts, characterized in that compounds of the formula where R1 is a straight or branched alkyl radical with at least 2 carbon atoms, X is an oxygen or sulfur atom or an NH group or a: methylene radical (which may also contain alkyl radicals, in a known manner in salts of aromatic amino, oxy- , Diamino, dioxy, amino-oxycarboxylic or sulfonic acids transferred.