Deprotection – removal of amine protecting groups (phthalimide and dimethylaminosulphonyl)

Phthalimide is a classical protecting group for amines whilst the dimethylaminosulphonyl group is a more modern, patent-free, protecting group¹.  Removal of these protecting groups is not always straightforward.  Hydrazine is commonly used to remove phthalimide but is a potentially hazardous reagent and produces insoluble phthalazine by-products.

Phthalimide can also be removed by treatment with dimethylamine which generates the mono-dimethylamide of phthalic acid which can be extracted in to base.  A recent example of this was presented at a recent Scinetific Update conference², see below.

Removal of the dimethylaminosulphonyl group was also described at a Scientific Update conference³.  Treatment of the dimethylaminosulphonylamine with 1,3-diaminopropane generates the amine along with some easily removed by-products (see below).

1 R.B.C. Jagt et al, Angew. Chem. Internat. Ed., 2006, 45, 2789.
2 C. Cobley (Dr Reddy’s), presentation at New Horizons in Catalysis, Clearwater, FL, November 2008.
3 D. Ager (DSM), presentation at Modern Synthetic Methods & Chiral Europe, Vilamoura, Portugal, May 2008.