Søren Ebdrup

Preparation of 3-substituted 10-methylphenothiazines

Lithiation at the C-3 position of 10-methylphenothiazine can be achieved by a BusLi–Br exchange reaction starting from 3-bromo-10-methylphenothiazine. Reaction of the lithiated species with different electrophiles gives rise to different new and well known compounds which due to their radical properties are important enzyme enhancers. The described procedure gives moderate to high yield and easy access to C-3 substituted derivatives.

Preparation of 4-substituted 10-ethylphenothiazines

Under appropriate reaction conditions 10-ethylphenothiazine 1 undergoes lithiation at C-4 using an excess of sec-butyllithium–N,N,N′,N′-tetramethylethane-1,2-diamine in diethyl ether. Reaction of the lithiated intermediate with a variety of carbon, halogen, sulfur and silicon electrophiles affords several new 4-substituted 10-ethylphenothiazines 3a–i in good yields.