Methods of chemical synthesis of diaminophenothiazinium compounds involving the use of persulfate oxidants

A method for the preparation of a diaminophenothiazinium compound, the method comprising one or both of the steps of (i) Thiosulfonic Acid Formation (TSAF);

• and (ii) Oxidative Coupling (OC);
• wherein the diaminophenothiazinium compound has the following formula:
• and:
• each of —R1 and —R9 is independently —H or —RA;
• and each —RA is independently selected from C1-4alkyl;
• C2-4alkenyl;
• halogenated C1-4alkyl;
• C5-10aryl;
• halogenated C5-10aryl;
• C1-4alkylene-C5-10aryl and halogenated C1-4alkylene-C5-10aryl;
• each of —R3NA and —R3NB is independently selected from:
• C1-4alkyl;
• C2-4alkenyl;
• halogenated C1-4alkyl;
• C5-ioaryl;
• halogenated C5-10aryl;
• C1-4alkylene-C5-10aryl and halogenate C1-4alkylene-C5-10aryl;
• each of —R7NA and —R7NB is independently selected from:
• C1-4alkyl;
• C2-4alkenyl;
• halogenated C1-4alkyl;
• C5-10aryl;
• halogenated C5-10aryl;
• C1-4alkylene-C5-10aryl and halogenated C1-4alkylene-C5-10aryl;
• and
• X− is an anionic counter ion;
• wherein step (i) Thiosulfonic Acid Formation (TSAF) comprises a step in which a compound of formula I is oxidized in the presence of a thiosulfate and an oxidizing agent that is or comprises persulfate to give a compound of formula II:
• wherein —R9, R7NA and —R7NB are as previously defined;
• and each of —R10NA and —R10NB is independently selected from:
• —H;
• C1-4alkyl;
• C2-4alkenyl;
• halogenated C1-4alkyl;
• C5-10aryl;
• halogenated C5-10aryl;
• C1-4alkylene-C5-10aryl and halogenated C1-4alkylene-C5-10aryl;
• and wherein step (ii) Oxidative Coupling (OC) comprises a step in which a compound of formula IIa is oxidatively coupled to a compound of formula III, using an oxidizing agent that is or comprises persulfate, to give a compound of formula IV:
• wherein:
• each of —R1 and —R9 is independently —H or —RA;
• —RA, —R3NA, —R7NA and —R7NB are as previously defined.