Compared with many other drugs, paracetamol is much easier to synthesize, because it lacks stereocenters. As a result, there is no need to design a stereo-selective synthesis.
Industrial preparation of paracetamol usually proceeds from nitrobenzene.[24] A one-step reductive acetamidation reaction can be mediated by thioacetate.[25]
Paracetamol may be easily prepared in the laboratory by nitrating phenol with sodium nitrate, separating the desired p-nitrophenol from the ortho- byproduct, and reducing the nitro group with sodium borohydride. The resultant p-aminophenol is then acetylated with acetic anhydride.[26] In this reaction, phenol is strongly activating, thus the reaction only requires mild conditions (c.f. the nitration of benzene):
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