Patent GB-1304367-A (GB)
IPC: C07F9/50
Filed: 1969-06-11
Abstract: 1304367 Macrocyclic compounds SCHERICO Ltd 5 June 1970 [11 June 1969 17 Feb 1970] 29564/69 and 7594/70 Headings C2C and C2P Novel macrocyclic compounds of the general Formula I wherein each of R 1  is hydrogen, C 1-12  hydrocarbon or alkoxycarbonyl having up to 10 carbon atoms or both R 1  form together a grouping of the general Formula II (i.e. providing a bridge between the two X groups in the molecule); each A is a C 1-12  hydrocarbon; each X is nitrogen or phosphorus; each D is oxygen, sulphur, >N-R (R being hydrogen or a C 1-12  hydrocarbon) or a C 1-12  hydrocarbon, with the proviso that at least two of the groups or atoms D are selected from oxygen, sulphur and >N-R, and that when each R 1  is hydrogen, hydrocarbon or alkoxycarbonyl and both X are nitrogen, then one of these two groups or atoms represented by D is oxygen or sulphur and the other is oxygen or >N-R; and each of m, n and p is a whole number from 0 to 5 inclusive; and also the phosphonium and/or ammonium salts, the nitrogen and/or phosphorus oxides of tertiary nitrogen and or phosphorus, and complexes formed from I and from the N- and/or P-oxides, with organic or inorganic cations may be prepared by condensing III and IV wherein Y is selected from R 1 NHCO-, R 1 NH- and R 2 R 3 X- where R 2  is a hydrogenolysable group and R 3  is the same as R 2  or R 1 , and V is a leaving group which is sufficiently labile to be displaced by Y; or Y is the grouping R 1 NH- and V is the group halogen -CO-; both condensations being performed using high dilution techniques; and reducing any carbonyl groups in the product to methylene optionally followed by (a) hydrogenolysis of any hydrogenolysable groups R 2  and/or R 3 ; (b) formation of a phosphonium and/or ammonium salt; (c) formation of any phosphonium and/or ammonium salt into a free compound; (d) formation of N- and/or P-oxide; (e) formation of a complex with organic or inorganic cations; (f) formation of the free compound from a complex or (g) repetition of the initial process to form the bridged structures. 1,8-Diamino-3,6-dioxaoctane may be prepared by bromination of triethylene glycol to yield triethylene glycol dibromide which is converted to triethylene glycol diphthalimide which is reduced to the required compound. 1,11- Diamino-3,6,9-trioxaundecane and 1,5-diamino- 3-oxapentane may be prepared from tetraethylene glycol and 1,5-dichloro-3-oxapentane respectively by similar processes. Triglycolyl chloride may be prepared by oxidation of triethylene glycol to triglycolic acid followed by formation of the acid chloride. Tetraglycolyl chloride may be prepared from tetraethylene glycol by a similar process. Ethylene-bisthioglycolic acid chloride may be prepared by condensing thioglycolic acid with dibromoethane to yield ethylene-bisthioglycolic acid which is converted to its acid chloride. Similarly 3,6-dithia-1,8-diamino-octane may be prepared by condensation of cysteamine with dibromoethane. Diglycolic acid dichloride may be formed from its free acid. Tetraglycolic acid may be purified by converting its acid chloride to tetra glycolic acid dianilide and hydrolysing the dianilide to the free acid. Monothio-triglycolic acid dichloride may be prepared by reaction of 2-chloroethanol with trioxymethylene to yield 2-chloroethyl-chloromethyl ether which with cuprous cyanide yields 2-chloroethoxy acetonitrile which is hydrolysed to 2-chloroethoxyacetic acid which is condensed with this glycolic acid to yield monothio-triglycolic acid which may be converted to the acid chloride. 1,2-Di-(chlorocarbonyl-methoxy)-benzene may be prepared by condensation of pyrocatechol with monochloracetic acid to form 1,2-di- (carbonyl-methoxy) -benzene which is converted to the required diacid chloride. 3,6 - dioxa - 1,8 - bis(dibenzylphosphine) octane may be prepared by reaction of triethylene glycol dibromide with tribenzylphosphine to yield 3,6-dioxa-1,8-bis(tribenzylphosphonium) octane dibromide which is reduced to the required free phosphine. The complexing properties of the compounds I enable their use as chelating agents for example in desalination and separation of metals The compounds I may also be used for catalysis in ionic reactions in a polar organic media. Pharmaceutical compositions of the compounds I may be used for regulation of cation exchange, show antiviral activity against A 2  influenza and tests indicate use in the treatment of diabetes and hyperlipema.