[219511-71-4] C₆H₁₃N₃O₂ (MW 159.19)

InChI = 1S/C6H13N3O2/c1-6(2,3)11-5(10)9-4(7)8/h1-3H3,(H4,7,8,9,10)

InChIKey = UMOZLQVSOVNSCA-UHFFFAOYSA-N

(used as guanidinylating agent and for synthesis of 2-aminoimidazoles)

Physical Data: mp 196–197 °C.¹

Solubility: soluble in most alcohols, esters (e.g., ethyl acetate), ketones (e.g., acetone), acetonitrile, and dichloromethane. Not soluble in diethyl ether and hexane.

Purification: for most applications, Boc-guanidine may be used as obtained after synthesis. Possible impurities are di- and tri-Boc-guanidine. Further purification is possible by crystallization from ethyl acetate and light petroleum.¹

Preparative Method: the original synthesis was reported by Buchinska.¹ A modified protocol for handling of larger quantities is as follows. To a cooled (0 °C) solution of guanidine hydrochloride (5 equiv, 275 mmol, 26.3 g) in aqueous sodium hydroxide (50 mL, 5.5 equiv, 303 mmol, 12.1 g) a solution of di-tert-butyl dicarbonate (1 equiv, 55 mmol, 12.0 g) in dioxane (100 mL) was added slowly (8 h). The reaction mixture was stirred for 20 h at room temperature. After extraction with ethyl acetate, the combined organic phases were dried (MgSO₄) and the solvent evaporated under reduced pressure. The resulting colorless crystals were dried in vacuo to yield 97% of Boc-guanidine (8.51 g, purity ca. 90%).^{1, 2}.

Handling, Storage, and Precautions: avoid contact with acids because of decomposition of the Boc-protecting group to CO₂ and isobutylene as by-products. In aqueous solution, the Boc group is stable under basic conditions and inert to many nucleophilic reagents.³ Stability tests of di-Boc-guanidine (which should behave in a similar manner) were performed in solutions of acetonitrile and water with HOAc, TFA, and HCl 10% each. After 13 h reaction time, decomposition of di-Boc-guanidine to the extent of 25–35% (HOAc), 40–50% (TFA) and 85–95% (HCl) was observed.