Sulfuric acid (H2SO4) has been employed for the sulfation of (cyclo)alkenes at modest temperature and pressure resulting in (cyclo)alkyl sulfates and the sulfation of polysaccharides and flavonoids. [25] The high reactivity of sulfuric acid can be modified via the sulfamic acid (H2NSO3H) reagent, which has been used for the sulfation of saturated alcohols, carbohydrate, and flavonoids including the naturally occurring triterpenoid betulin which is found in the bark of birch trees which possesses anti-viral, anti-inflammatory, anti-oxidant, and anti-coagulant properties. Betulin was sulfated using the sulfamic acid method in the presence of an urea CO(NH2)2 catalyst and alternatively DMF or 1,4-dioxane as solvent. Double sulfation of betulin was achieved and isolated as ammonium, sodium, and potassium salts (Scheme 2). Scheme 2. Double sulfation of betulin with sulfamic acid (NH2SO3H). Conditions: (i) NH2SO3H, urea, DMF (60-70°C was 2.0-3.0 h) or 1,4-dioxane (70-75°C, 3.0-3.5 h); (ii) work up with 10% H2SO4, or 3-5% KOH, or 3-5% NaOH.