US 12,215,234 B2
Process for the purification of methylene blue
Ravishanker Kovi, Monroe Township, NJ (US); Jayaraman Kannappan, Vadodara (IN); Hemant Mande, Gujarat (IN); and Dusanapudi Naga Venkata Raghavulu, Vadodara (IN)
Assigned to RK Pharma Solutions LLC, Piscataway, NJ (US)
Filed by RK Pharma Solutions LLC, Piscataway, NJ (US)
Filed on Sep. 17, 2020, as Appl. No. 17/023,544.
Claims priority of application No. 201921038163 (IN), filed on Sep. 21, 2019.
Prior Publication US 2022/0049102 A1, Feb. 17, 2022
Int. Cl. C09B 21/00 (2006.01)
CPC C09B 21/00 (2013.01) 2 Claims
 
1. A method for producing methylene blue comprising:
a) providing a reaction mixture comprising one or more methylene blue intermediates;
b) reducing the metal content therein by precipitation during solvent extraction under basic conditions wherein the basic condition is between about pH 9 and about pH 11; to form a reaction mass;
c) producing crude methylene blue by further adjusting the pH of the reaction mass to an acidic pH with acid;
d) purifying the crude methylene blue by treatment with polar solvent to remove the impurity at 0.94 RRT;
e) producing methylene blue having purity greater than about 97% by repeating steps (b) and (c) followed by purification using water and THF; wherein, providing the reaction mixture comprises,
I. reacting N,N-dimethylaniline

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N,N-dimethylaniline
with sodium nitrite in hydrochloric acid to obtain an in-situ nitroso compound;

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nitroso compound
II. reducing the in-situ nitroso compound

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nitroso compound
in the presence of zinc and hydrochloric acid to obtain in-situ p-amino-N,N-dimethyl aniline;

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p-amino-N,N-dimethyl aniline
III. reacting the in-situ p-amino-N,N-dimethyl aniline

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p-amino-N,N-dimethyl aniline
with sulfuric acid and zinc chloride in the presence of sodium thiosulfate pentahydrate, sodium dichromate, and aluminium sulphate octahydrate to obtain an in-situ thiosulfonic acid compound;

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thiosulfonic acid compound
IV. treating the in-situ thiosulfonic acid compound

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thiosulfonic acid compound
with another molecule of N,N-dimethylaniline in the presence of sodium dichromate and zinc chloride to yield an in-situ di-cyclic compound;

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Di-cyclic compound
and
V. allowing the in-situ di-cyclic compound

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Di-cyclic compound
to undergo a cyclisation reaction in the presence of manganese oxide to yield methylene blue crude;

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Methylene blue crude.