1,6-di(N.sup.3 -cyano-N.sup.1 -guanidino) hexane, often designated as hexamethylene-bis-cyanoguanidine or hexamethylene-bisdicyandiamide, is a valuable intermediary product for the preparation of bisbiguanides and polybiguanides, which are used as disinfectants or pesticides (cf. e.g. British Patent 705,838 and Published European Patent Specifications EP 125,091; EP 125,092; EP 125,093; EP 126,567; EP 127,062).
One of the most important uses for 1,6-di(N.sup.3 -cyano-N.sup.1 -guanidino) hexane is the manufacture of 1,6-di(N.sup.5 -p-chlorophenyl-N.sup.1 -diguanido)-hexane, generally designated as chlorhexidine. Chlorhexidine is a very effective antibacterial and antiseptic agent against gram-positive and gramnegative bacteria.
Various methods have been described for preparing 1,6-di(N.sup.3 -cyano-N.sup.1 -guanidino) hexane:
F. L. Rose and G. Swain (J. Chem. Soc., (1956) pp. 4422 -4425) react sodium dicyanamide and hexamethylene diamine dihydrochloride with each other in stoichiometric proportions in n-butanol by heating for 8 hours under reflux. The reaction proceeds according to the following equation: ##STR1##
The raw product of the desired 1,6-di(N.sup.3 -cyano-N.sup.1 -guanidino) hexane (I) which crystallizes out during cooling is filtered off together with sodium chloride which is formed and is present in an undissolved state. The product is subsequently washed with water and then dried. The yield of the product designated (I) should be 70 to 80 %. Nothing is said about the purity of (I); however, the indicated melting point of the product recrystallized from water (202.degree.-203.degree. C.) is still clearly under that of a pure product (209.degree.-210.degree. C.). Experiments performed by the applicant according to information in this document yielded contents of (I) of approximately 90 %. Therefore, the process suffers from the low product purity, which makes itself apparent in a reduced yield during the reaction to make chlorhexidine, and also in the moderate yield. In addition, the equipment expenses and the long reaction time required for this process result in a low space-time yield.
U.S. Pat. No. 4,537,746 describes an example of preparing 1,6-di(N.sup.3 -cyano-N.sup.1 -guanidino) hexane (I) according to the method of Rose et al. and clearly refers to the document evaluated above.
The raw product (I) with a melting point of 200.degree.-203.degree. C. must be recrystallized in this case from a very large volume of a methanol-water mixture in order to obtain a product quality which is required for the subsequent reactions to produce disinfectants. The inventor has repeated this example. Instead of the 94 % yield described by this patent, only a yield of 45 % (63 % raw product) was obtained; moreover, the product purity after recrystallization was only 93.3 %. The example of U.S. Patent 4,537,746 provides no information on the quality of the sodium dicyanamide used - 1 mole corresponds to 89 g; however, 103 g were used.
J. Burns (J. Labelled Comp. Radiopharm. 19, 1982, pp. 1239-1250) discloses a method of preparing (I) in which the substances used in the previously cited methods are reacted with each other. Sodium dicyanamide is added in a slight excess in this process and the solvent is isopropanol dried with a molecular sieve. This method requires a 16-hour reaction time and produces (I) in a 57 % yield.
According to Published German Patent Specification DE-OS 29 32 951, 1,6-di(N.sup.3 -cyano-N.sup.1 -guanidino) hexane can also be prepared by reacting hexamethylene diamine with an N-cyano-O (or S)-alkyl-iso (or isothio)-urea. The preparation of the urea starting material proceeds via the reaction of oxygen or thio-esters of N-cyanoimino carbonic acid with ammonia or an ammonium carbonate; the reaction with hexamethylene diamine takes place under pressure and requires a very long reaction time. Subsequently, the product must be purified with water and alcohol. Disadvantages of this and similar methods (cf. HU-PS 17,484 and 15,453) are the requirement for working under pressure, the very long reaction times, the formation of mercaptans when isothioureas are used, the use of expensive starting materials and the expense associated with the purification of the desired final product (I).