Acid-Mediated C–N Bond Cleavage in 1-Sulfonylpyrrolidines: An Efficient Route towards Dibenzoxanthenes, Diarylmethanes, and Resorcinarenes

Abstract

The rare example of pyrrolidine C–N bond cleavage in 1-sulfonylpyrrolidines in acidic media in the presence of phenols is reported. The reaction proceeds under mild conditions and provides a convenient route to otherwise hardly accessible and previously unknown dibenzoxanthenes, diarylbutanes, and resorcinarenes having a sulfonylamide moiety.

Key words

ring opening - sulfonamides - heterocycles - pyrrolidines - macrocycles - diarylmethanes - dibenzoxanthenes

• References and Notes

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• 30 General Method for the Synthesis of Dibenzoxanthenes 3 To a solution of pyrrolidine 2 (1.27 mmol) or acetal 1 (1.25 mmol) and 2-naphthol (0.37 g, 2.54 mmol) in dry CHCl₃ (5 mL) TFA (2 mL) was added. The reaction mixture was stirred at r.t. for 24 h. Then the solvent was removed, the residue washed with Et₂O (5 mL), and dried under vacuum (1 h, 0.01 Torr, r.t.) to give the desired product 3. General Method for the Synthesis of Diarylbutanes 4 To a solution of pyrrolidine 2 (1.27 mmol) or acetal 1 (1.27 mmol) and 4-chlororesorcinol (0.37 g, 2.54 mmol) in dry CHCl₃ (5 mL) TFA (2 mL) was added. The reaction mixture was stirred at r.t. for 24 h. Then the solvent was removed, the residue washed with Et₂O (5 mL), and dried under vacuum (1 h, 0.01 Torr, r.t.) to give the desired product 4. General Method for the Synthesis of Calixarenes 5, 6 To a solution of pyrrolidine 2 (1.27 mmol) or acetal 1 (1.27 mmol) and the appropriate phenol (1.27 mmol) in dry CHCl₃ (5 mL) TFA (2 mL) was added. The reaction mixture was stirred at r.t. for 24 h. Then the solvent was removed, the residue washed with Et₂O (5 mL), and dried under vacuum (1 h, 0.01 Torr, r.t.) to give the desired product 5 or 6. N-[3-(14H-Dibenzo[a,j]xanthen-14-yl)propyl]methanesulfonamide (3c) White solid (0.30 g, 56% from pyrrolidine 2c), mp 145–146 °C. ¹H NMR (400 MHz, (CD₃)₂SO): δ = 1.03–1.13 (m, 2 H, CH₂), 1.90–2.00 (m, 2 H, CH₂), 2.57 (s, 3 H, СН₃), 2.56–2.64 (m, 2 H, CH₂), 5.69–5.77 (m, 1 H, CH), 6.64 (t, ³ J _HH = 5.9 Hz, 1 H, NH), 7.45 (d, ³ J _HH = 8.8 Hz, 2 H, CH_Ar), 7.51 (t, ³ J _HH = 7.4 Hz, 2 H, CH_Ar), 7.68 (t, ³ J _HH = 7.6 Hz, 2 H, CH_Ar), 7.91 (d, ³ J _HH = 8.8 Hz, 2 H, CH_Ar), 7.97 (d, ³ J _HH = 8.0 Hz, 2 H, CH_Ar), 8.55 (d, ³ J _HH = 8.5 Hz, 2 H, CH_Ar). ¹³C NMR (150 MHz, (CD₃)₂SO,): δ = 25.7, 30.3, 33.6, 39.5, 42.9, 116.9, 117.7, 123.6, 124.9, 127.4, 129.0, 129.2, 131.2, 131.6, 149.9. IR (KBr): ν = 1145, 1325, 1591, 2862, 2939, 3060, 3312 cm^–1. MALDI TOF: m/z = 440 [M + Na], 456 [M + K]. Anal. Calcd (%) for C₂₅H₂₃NO₃S: C, 71.92; H, 5.55; N, 3.09; S, 7.81. Found: C, 72.15; H, 5.69; N, 3.09; S, 7.81. N-[4,4-Bis(5-chloro-2,4-dihydroxyphenyl)butyl]-4-methylbenzenesulfonamide (4a) White solid (0.42 g, 65% from pyrrolidine 2a, 0.48 g, 74% from acetal 1a), mp 145–147 °C. ¹H NMR (400 MHz, (CD₃)₂SO): δ = 1.13–1.29 (m, 2 H, CH₂), 1.67–1.77 (m, 2 H, CH₂), 2.37 (s, 3 H, СН₃), 2.67–2.75 (m, 2 H, CH₂), 4.16 (t, ³ J _HH = 7.8 Hz, 1 H, CH), 6.43 (s, 2 H, CH_Ar), 6.84 (s, 2 H, CH_Ar), 7.34 (d, ³ J _HH = 8.0 Hz, 2 H, CH_Ar), 7.38 (t, ³ J _HH = 5.9 Hz, 1 H, NH), 7.61 (d, ³ J _HH = 8.2 Hz, 2 H, CH_Ar), 9.25 (s, 2 H, OH), 9.65 (s, 2 H, OH). ¹³C NMR (150 MHz, (CD₃)₂SO): δ = 21.4, 28.2, 31.2, 35.8, 43.2, 104.1, 109.4, 123.5, 126.9, 128.8, 130.0, 138.3, 142.8, 151.6, 154.7; IR (KBr): ν = 1152, 1598, 2867, 2943, 3286, 3428 cm^–1. MALDI TOF: m/z = 534 [M + Na], 550 [M + K]. Anal. Calcd (%) for C₂₃H₂₃Cl₂NO₆S: C, 53.91; H, 4.52; Cl, 13.84, N, 2.73; S, 6.26. Found: C, 52.17; H, 4.41; Cl, 14.00, N, 2.49; S, 6.07. N,N′,N′′,N′′′-{[14,16,34,36,54,56,74,76-Octahydroxy-1,3,5,7(1,3)-tetrabenzenacyclooctaphane-2,4,6,8-tetrayl]tetrakis(propane-3,1-diyl)}tetrakis(4-methylbenzenesulfonamide) (5a) White solid (0.38 g, 89% from pyrrolidine 2a, 0.39 g, 94% from acetal 1a), mp 169–170 °C. ¹H NMR (400 MHz, (CD₃)₂SO): δ = 1.18–1.29 (m, 8 H, CH₂), 1.91–1.99 (m, 8 H, CH₂), 2.36 (s, 12 H, CH₃), 2.67–2.74 (m, 8 H, CH₂), 4.10 (t, ³ J _HH = 7.8 Hz, 4 H, CH), 6.12 (s, 4 H, CH_Ar), 7.04 (s, 4 H, CH_Ar), 7.32 (d, ³ J _HH = 8.1 Hz, 8 H, CH_Ar), 7.36 (t, ³ J _HH = 5.6 Hz, 4 H, NH), 7.61 (d, ³ J _HH = 8.1 Hz, 8 H, CH_Ar), 8.86 (s, 8 H, OH). ¹³C NMR (150 MHz, (CD₃)₂SO): δ = 21.4, 28.2, 31.0, 32.9, 43.0, 102.8, 123.3, 125.3, 126.9, 130.0, 138.3, 142.9, 152.2; IR (KBr): ν = 1154, 1599, 2871, 2939, 3302 cm^–1. MALDI TOF: m/z = 1355 [M + Na], 1371 [M + K]. Anal. Calcd (%) for C₆₈H₇₆N₄O₁₆S₄: C, 61.24; H, 5.74; N, 4.20; S, 9.62. Found: C, 61.01; H, 5.59; N, 3.92; S, 9.90.
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