Patent GB-774794-A (GB)
Title: Quinone condensation products
IPC: C07C281/18
Filed: 1953-12-24
Abstract: The invention comprises N-guanidino-N1-acylamino-p-quinone di-imides, wherein the quinone residue may optionally contain alkyl substituents of up to 3 carbon atoms, N : N1-bis - (N11 - acylamino - p - quinone - di - imido) derivatives of bis-guanides and N : N1-bis-(N11-guanidino-p-quinone-di-imido) derivatives of diamides, the acyl-amino groups being ureido, thioureido or carboxylic acid amido radicals; the invention comprises also salts and dihydro derivatives of these compounds.  The products are made by reacting a p-quinone with an aminoguanidine to form a N-guanidino-p-quinone imide which is then reacted with a semicarbazide, thiosemicarbazide or carboxylic acid hydrazide, or alternatively by treating the quinone first with the acid hydrazide and then with the aminoguanidine, the reactants preferably being present in equimolecular quantities.  For the preparation of the above bis-compounds, either the aminoguanidine is a bis-aminoguanidine, such as hexamethylene-1 : 6-bis-aminoguanidine, or the acyl hydrazide is a bis-compound such as hexamethylene-1 : 6-bis-thiosemicarbazide or the hydrazides of oxalic, succinic, adipic or terephthalic acid, preferably using 1/2 mol. of bis-reactant to each mol. of quinone and mono-hydrazide.  The aminoguanidine may be unsubstituted or substituted, e.g. by alkyl or aryl groups, or the two nitrogen atoms of the guanidine configuration may be incorporated in a heterocyclic ring, as in 2-hydrazino-imidazoline or 1-methyl-2-hydrazino-1:4:5:6 - tetrahydropyrimidine.  The dihydro derivatives are made by treating the condensation products with reducing agents such as zinc and hydrochloric acid, stannous chloride or sodium dithionite.  The compounds are used as pharmaceuticals.  The salts are preferably salts in which the acidic component is an acidic reacting therapeutic compound. Examples describe the preparation of N-guanidino-N1-substituted-p-benzoquinone di-imides in which the N1 - substituents are thioureido -, allyl - thioureido-, methyl-thioureido-, ethyl-thioureido-, propyl-thioureido-, butyl-thioureido-, isobutyl-thioureido-, tert.-butyl-thioureido-, cyclohexyl-thioureido-, benzyl-thioureido-, benzthiazolylamino-, p - nitrobenzoyl - amino -, cyano-acetyl-amino-, oxamoylamino-, benzamido-, p-chlorobenzamido-, 2:4-dichlorobenzamido-, phydroxybenzamido -, m - nitrobenzamido-, p - aminobenzamido-, isonicotinyl - amido -, ureido-, guanyl - ureido -, butyl - ureido - and phenyl-ureido-groups; also the preparation of N - (2 - imidazolinyl - amino) - N1 - thioureido - p-quinone-di-imide; hexamethylene - 1:6 - bis-(thioureido - quinonedi-imido - guanidine); N-(2 - imidazolinyl - amino) - N1 - (allyl - thioureido) - p - quinonedi-imide and bis - (N - guanidino - p - quinonedi-imido) - adipic acid diamide; salts and dihydro-derivatives of some of the above compounds are also described.  Intermediates.  N - Guanidino - quinone - monoimides and N - acylamino - quinone - monoimides in which the acyl groups are ureido, thioureido or carboxylic acid amide groups are formed as intermediates.  Specified compounds include N - (2 - imidazolinyl - amino) - p - quinoneimide, hexamethylene - 1:6 - bis - (p - quinoneimido - guanidine) and N - guanidino - p - quinone-imides.  2-Hydrazino-imidazoline is prepared by the reaction of hydrazine and 2-ethylmercapto-2-imidazoline.ALSO:Dyestuffs and intermediates for dyes comprise N - guanidino - N1 - acylamino-p-quinone diimides, wherein the quinone residue may optionally contain alkyl groups of up to 3 carbon atoms as substituents, N:N1 - bis(N11 - acylamino - p - quinonediimido) derivatives of bis-guanides and N:N1 - bis(N11 - guanidino - p - quinone - diimido) derivatives of diamides, the acylamino groups being ureido, thioureido or carboxylic acid amido radicals; the invention comprises also salts and dihydro derivatives of these compounds.  The products are made by reacting a p-quinone with an aminoguanidine to form a N-guanidino-p-quinone imide which is then reacted with a semicarbazide, thiosemicarbazide or carboxylic acid hydrazide, or alternatively by treating the quinone first with the acid hydrazide and then with the aminoguanidine, the reactants preferably being present in equimolecular quanties.  For the preparation of the above bis-compounds, either the aminoguanidine is a bis-aminoguanidine, such as hexamethylene-1:6-bis-aminoguanidine, or the acyl hydrazide is a bis-compound such as hexamethylene - 1.6 - bis - thiosemicarbazide or the hydrazides of oxalic, succinic, adipic or terephthalic acid, preferably using 1/2 mol of bis-reactant to each mol of quinone and mono-hydrazide.  The aminoguanidine may be unsubstituted or substituted, e.g. by alkyl or aryl groups, or the two nitrogen atoms of the guanidine configuration may be incorporated in a heterocyclic ring, as in 2-hydrazino-imidazoline or 1-methyl-2-hydrazino-1:4:5:6-tetrahydropyrimidine.  The dihydro derivatives are made by treating the condensation products with reducing agents such as zinc and hydrochloric acid, stannous chloride or sodium dithionite.  The compounds are used as pharmaceuticals. The salts are preferably salts in which the acidic component is an acidic reacting therapeutic compound. Examples describe the preparation of N-guanidino-N1-substituted-p-benzoquinone diimides in which the N1-substituents are thioureido-, allyl - thioureido-, methyl - thioureido-, ethyl - thioureido-, propyl - thioureido-, butyl - thioureido-, isobutyl - thioureido-, tert - butyl - thioureido-, cyclohexyl - thioureido, benzyl - thioureido, benzthiazolyl - amino-, p - nitrobenzoyl - amino -, cyanoacetyl - amino-, oxamoylamino-, benzamido-, p - chlorobenzamido-, 2 : 4 -dichlorobenzamido-, p - hydroxybenzamido-, m - nitrobenzamido-, p - aminobenzamido-, isonicotinyl - amido-, ureido-, guanyl - ureido-, butyl - ureido- and phenyl - ureido - groups; also the preparation of N-(2 - imidazolinyl - amino)-N1 - thioureido - p - quinone - diimide; hexamethylene - 1 : 6 - bis(thioureidoquinonediimido - guanidine); N-(2 - imidazolinyl-amino) - N1 - (allyl - thioureido)-p-quinonediimide and bis-(N-guanidino-p-quinonediimido)-adipic acid diamide; salts and dihydro-derivatives of some of the above compounds are also described.  Intermediates.  N-Guanidino quinonemonoimides and N-acylamino-quinonemonoimides in which the acyl groups are ureido, thioureido or carboxylic acid amide groups are formed as intermediates.  Specified compounds include N-(2-imidazolinyl - amino) - p - quinone-imide, hexamethylene - 1:6 - bis - (p - quinone-imidoguanidine) and N-guanidino-p-quinoneimide. Hydrazino-imidazoline is prepared by the reaction of hydrazine and 2-ethylmercapto-2-imidazoline.ALSO:Pharmaceutical products having bactericidal or bacteriostatic activity comprise N-guanidino-N1 - acylamido - p - quinone diimides, wherein the quinone residue may optionally contain alkyl groups of up to 3 carbon atoms as substituents; N : N1 - bis (N11 - acylamino p - quinonediimido) derivatives of bis guanides; N : N1 - bis (N11-guanidino - p - quinonediimido) derivatives of diamides and salts and dihydro derivatives of these compounds, the acylamino groups being ureido, thioureido or carboxylic acid amido radicals (see Group IV(b)).  In an example (8) a solution of 1 part of N-guanidino -N1-thioureido - p-quinonediimide and 1 or 2 parts of ascorbic acid is prepared and heated to effect reduction of the quinonediimide derivative to its dihydro derivative; the solutions are suitable for medical use.