Patent GB-461245-A (GB)
Title: Improvements in or relating to the manufacture of n-polyhydroxy-alkyl-phenylenediamines
Filed: 1935-08-07
Abstract: N - Glycosido - o - nitranilines ("glycosido" meaning a residue of a pentose or a hexose) are obtained by heating an o-nitroamino compound of the benzene series with a pentose or a hexose in the presence of an inert solvent.  The reaction does not proceed to completion, but the equilibrium point can be shifted in the desired direction by addition of an ammonium halide or alkylated ammonium halide, e.g. ammonium chloride, methyl-, dimethyl- or trimethylaminehydrochloride, or tetramethylammonium chloride.  The N-glycosido compound may be separated from unchanged starting materials by adsorption, preferably by chromatographic adsorption.  When a pentose is used, the product contains only three acetylatable hydroxy groups, and when a hexose is used only four acetylatable hydroxy groups are present.  The N-glycosido-o-nitranilines can be converted by reduction into N-glycosido-o-phenylenediamines or N-polyhydroxyalkyl-o-phenylenediamines.  Reduction to N-glycosido-o-phenylenediamines is effected under mild conditions, e.g. by catalytic hydrogenation at normal temperature and pressure in the presence of a small proportion of a catalyst and preferably in the presence of an organic base, e.g. trimethylamine or triethylamine; preliminary acylation of the N-glycosido-o-nitraniline and subsequent removal of the acyl groups may be advantageous. Reduction to N-polyhydroxyalkyl-o-phenylenediamines is preferably effected by catalytic hydrogenation at a raised temperature and pressure in the presence of a relatively large proportion of a relatively active hydrogenation catalyst, e.g. nickel, platinum or palladium, and advantageously with the addition of a weakly alkaline borate buffer, e.g. monosodium and potassium borate; other reducing agents, e.g. zinc dust or aluminium amalgam, may also be used. Both the N-glycosido-o-phenylenediamines and the N - polyhydroxyalkyl-o-phenylenediamines can be condensed with alloxan, by the process described in Specification 441,692, to yield isoalloxazines correspondingly substituted in the 9-position.  In the examples: (1) 4 : 5-dimethyl-2-nitraniline and d-ribose are heated in alcoholic solution at atmospheric or raised pressure to yield 1 - (d-ribosidoamino)- 4 : 5 - dimethyl - 2 - nitrobenzene, the isolation of which by chromatographic adsorption with aluminium oxide is described; the product yields a triacetyl derivative by reaction with acetic anhydride in the presence of pyridine; reduction in alcoholic solution with hydrogen at a superatmospheric pressure of 1 atm. in the presence of platinum oxide yields a mixture of 1-(d-ribosidoamino)-and 1-(d-ribitylamino)-2-amino-4 : 5-dimethylbenzenes, which by condensation with alloxan yields 6 : 7-dimethyl-9-d-ribosido- and 6 : 7-dimethyl - 9 - d - ribityl - isoalloxazines; (2) 4 : 5-dimethyl-2-nitraniline and l-arabinose, as in example 1, yield 1-(l-arabinosidoamino)-4 : 5-dimethyl-2-nitrobenzene, the triacetyl derivative of which is treated in methyl acetate solution with hydrogen at 20 DEG  C. and a superatmospheric pressure of 1 atm. in the presence of platinum oxide; the reduction product, by reaction with alloxan in the presence of boric and acetic acids, yields 9-(triacetylarabinosido)-6 : 7-dimethylisoalloxazine, from which 9-(l-arabinosido) - 6 : 7 - dimethylisoalloxazine is obtained by saponification with ammoniacal methyl alcohol, while saponification with dilute hydrochloric acid yields 6 : 7-dimethylalloxazine by rearrangement of a double bond; 4 : 5-dimethyl - 2 - nitraniline may be condensed similarly with d-arabinose, glucose and fructose to yield the corresponding 1-glycosidoamino-4 : 5-dimethyl-2-nitrobenzenes; (3) o-nitraniline and d-arabinose, heated in alcoholic solution in the presence of acetic acid, yield 1-(d-arabinosidoamino)-2-nitrobenzene; (4) the same starting materials as in example 1 are heated in alcoholic solution in the presence of ammonium chloride or a hydrochloride, hydrobromide or hydroiodide of mono-, di- or tri-methylamine, ethylamine, propylamine or an ethanolamine; (5) as in example 4, o-nitraniline is condensed with d-glucose, l-arabinose and d-xylose, and 4 : 5-dimethyl-2-nitraniline is condensed with l- and d-arabinose; the triacetyl derivatives of the products are mentioned; (6) 1-(d-ribosidoamino)-4 : 5-dimethyl-2-nitrobenzene (example 1) is hydrogenated in alcoholic solution at 50--60 DEG  C. and 40 atm. pressure in the presence of palladium-barium-sulphate and monosodium borate; 1 - (d - ribitylamino) - 2 - amino - 4 : 5-dimethylbenzene is obtained, and is condensed with alloxan.ALSO:N - Glycosido - o - nitranilines ("glycosido" meaning a residue of a pentose or a hexose) are obtained by heating an o-nitroamino compound of the benzene series with a pentose or a hexose in the presence of an inert solvent, and are converted by reduction into N-glycosido-o-phenylediamines or N-polyhydroxyalkyl-o-phenylenediamines.  Reduction to N-glycosido-o-phenylenediamines is effected under mild conditions, e.g. by catalytic hydrogenation at normal temperature and pressure in the presence of a small proportion of a catalyst and preferably in the presence of an organic base, e.g. trimethylamine or triethylamine; preliminary acylation of the N-glycosido-o-nitraniline and subsequent removal of the acyl groups may be advantageous. Reduction to N-polyhydroxyalkyl-o-phenylenediamines is preferably effected by catalytic hydrogenation at a raised temperature and pressure in the presence of a relatively large proportion of a relatively active hydrogenation catalyst, e.g. nickel, platinum or palladium, and advantageously with the addition of a weakly alkaline borate buffer, e.g. monosodium and potassium borate.  In the examples: (1) 4 : 5-dimethyl-2-nitraniline and d-ribose are heated in alcoholic solution at atmospheric or raised pressure to yield 1-(d-ribosidoamino)-4 : 5-dimethyl-2-nitrobenzene, which by reduction in alcoholic solution with hydrogen at a superatmospheric pressure of 1 atm. in the presence of platinum oxide yields a mixture of 1-(d-ribosidoamino)- and 1-(d-ribitylamino) - 2 - amino - 4 : 5 - dimethylbenzenes; (2) 4 : 5-dimethyl-2-nitraniline and 1-arabinose, as in example 1, yield 1-(l-arabinosidoamino)-4 : 5-dimethyl-2-nitrobenzene, the triacetyl derivative of which is treated in methyl acetate solution with hydrogen at 20 DEG  C. and a superatmospheric pressure of 1 atm. in the presence of platinum oxide; 4 : 5 - dimethyl - 2 - nitraniline may be condensed similarly with d-arabinose, glucose and fructose to yield the corresponding 1-glycosidoamino-5 : 5-dimethyl-2-nitrobenzenes; (3) 1 - (d - ribosidoamino) - 4 : 5 - dimethyl2-nitrobenzene (example 1) is hydrogenated in alcoholic solution at 50--60 DEG  C. and 40 atm. pressure in the presence of palladium-bariumsulphate and monosodium borate; 1-(d-ribitylamino)-2-amino-4 : 5-dimethylbenzene is obtained.