1 3-Bis(tert-butoxycarbonyl)guanidine

Uses

1,3-Bis(tert-butoxycarbonyl)guanidine may be used to produce a guanidinyl derivative during the multi-step synthesis of (-)-crispine E. It may also be used as a reagent during the preparation of 1,6-diphenylnaphthalenes.

General Description

1,3-Bis(tert-butoxycarbonyl)guanidine is a guanidine derivative. The synthesis of N-substituted 2-aminoimidazole inhibitors using 1,3-bis(tert-butoxycarbonyl)guanidine has been reported.

Synthesis

General procedure for the synthesis of the compound (CAS: 332882-82-3) from di-tert-butyl dicarbonate and guanidinium hydrochloride: guanidinium hydrochloride (12.3 g, 128 mmol) and sodium hydroxide (20.8 g, 519 mmol) were dissolved in water (125 mL) and 1,4-dioxane (250 mL) was added. The mixture was cooled to 0 °C and di-tert-butyl dicarbonate (62.9 g, 288 mmol) was added slowly. The reaction mixture was stirred at room temperature for 16 hours. Upon completion of the reaction, the solution was concentrated under vacuum to one-third of its initial volume. Water (150 mL) was added to the concentrate and extracted with ethyl acetate (3 x 80 mL). The organic phases were combined and washed sequentially with 10% aqueous citric acid (1 × 100 mL), water (1 × 100 mL) and saturated saline (1 × 100 mL). The organic phase was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain the crude product. The crude product was purified by rapid chromatography on silica gel (elution gradient: 100% dichloromethane to dichloromethane/methanol 95:5). N,N'-Di-Boc-protected guanidine was finally obtained as a white powder (30.54 g, 91% yield). The structure of the product was confirmed by the following characterization data: 1H NMR (300 MHz, DMSO-d6) δ 10.42 (s, 1H), 8.47 (s, 1H), 1.37 (s, 18H); 13C NMR (75.5 MHz, CDCl3) δ 158.3, 82.3, 28.1; IR (CHCl3) ν 3407, 3124 , 2976, 2930, 1792, 1641, 1549, 1453, 1397, 1365, 1128, 1153 cm-1.

References

[1] Patent: US9809621, 2017, B2. Location in patent: Page/Page column 31; 32
[2] Research on Chemical Intermediates, 2018, vol. 44, # 3, p. 1811 - 1832
[3] Journal of Organic Chemistry, 1998, vol. 63, # 12, p. 3804 - 3805
[4] Chemistry - A European Journal, 2014, vol. 20, # 32, p. 9910 - 9913
[5] Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 564 - 570