Iodine-Mediated Guanidine Formation through Arylsulfonyl-Activated Thioureas

Abstract

Reaction of arylsulfonyl thioureas with amines to form guanidines can be efficiently promoted through the use of iodine, instead of conventional reagents such as the Mukaiyama reagent or EDC. The general scope and limitations of the reaction are probed.

iodine - guanidine - arylsulfonyl thiourea - desulfurizations - aminations

References and Notes

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13

[ N -(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)- N ′-(2-ethoxycarbonylethyl)- N ′′-benzyl guanidine (5o): Iodine (0.0928 g, 0.35 mmol) was added to a solution of thiourea 3e (0.0495 g, 0.12 mmol) dissolved in THF (4 mL), followed by DIPEA (0.0491 g, 0.35 mmol). After 10 min, BnNH₂ (0.0388 g, 0.35 mmol) was added to the mixture, and the reaction mixture was stirred overnight at room temperature. The residue obtained after evaporation of the solvent was separated by silica gel column (petroleum ether-EtOAc) to afford 5o as a white solid (0.0364 g, 63%). MS: m/z = 502.3 [M + H]⁺. ^¹H NMR (300 MHz, CDCl₃): δ = 1.20-1.25 (t, J = 7.2 Hz, 3 H), 1.47 (s, 6 H), 2.10 (s, 3 H), 2.46-2.48 (d, J = 5.7 Hz, 2 H), 2.50 (s, 3 H), 2.58 (s, 3 H), 2.95 (s, 2 H), 3.44-3.50 (m, 2 H), 4.03-4.10 (m, 2 H), 4.30-4.32 (m, 2 H), 7.18-7.20 (m, 2 H), 7.29-7.31 (m, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 12.4, 14.1, 17.9, 19.2, 21.0, 28.6, 33.9, 36.9, 43.2, 45.4, 60.9, 86.3, 117.3, 124.4, 127.1, 127.8, 127.8, 132.3, 133.2, 138.4, 154.7, 158.6, 172.7. Anal. Calcd for C₂₆H₃₅N₃O₅S: C, 62.25; H, 7.03; N, 8.38. Found: C, 62.14; H, 7.12; N, 8.57.

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