K-10 Clay-Catalyzed Enol-Driven Decarboxylative Ring-Transformation Approach to Dihydro- and Tetrahydroquinolines from Carbohydrates

Abstract

An original synthetic approach to 4-polyhydroxyal­kylquinolines using unprotected d-glucose/d-xylose as biorenewable resources is reported. The synthetic protocol involves enol-driven Michael-type addition of cyclic ketones to aldose-derived 1,3-oxazin-2-ones followed by decarboxylative ring transformation to yield various novel 5,6-dihydro-/5,6,7,8-tetrahydro-4-polyhydroxyalkylquinolines and their 5-, 6-, or 8-one analogues. This is a one-pot montmorillonite K-10 clay-catalyzed process proceeding under solvent-free microwave irradiation conditions.

Key words

carbohydrates - mineral-catalyzed - microwaves - solvent-free - 1,3-oxazin-2-ones(thiones) - quinolines

References and Notes

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18

General Procedure for the Synthesis of 1,3-Oxazin-2-ones(thiones) 4: Thoroughly mixed d-xylose/d-glucose 1 (1 mmol), semicarbazide hydrochloride/thiosemicarbazide 2 (1 mmol), sodium acetate (1 mmol) and montmorillonite K-10 clay (0.10 g) in a 20-mL vial were subjected to microwave irradiation in a CEM Discover Focused Microwave Synthesis System for 10 min at 90 ˚C. After completion of the reaction as indicated by TLC, H₂O (10 mL) was added to precipitate the crude product, which was recrystallized from EtOH to afford analytically pure sample of 4.
Characterization Data of Representative Compounds: Compound 4a: white solid; yield: 82%; mp 145-148 ˚C. IR (KBr): 3392, 3386, 3011, 1692 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 4.11 (dd, J _{2 ′ Ha,2 ′ Hb} = 10.1 Hz, J _{1 ′ H,2 ′ Ha} = 5.4 Hz, 1 H, 2′H_a), 4.30 (dd, J _{1 ′ H,2 ′ Ha} = 5.4 Hz, J _{1 ′ H,2 ′ Hb} = 2.9 Hz, 1 H, 1′H), 4.63 (dd, J _{2 ′ Ha,2 ′ Hb} = 10.1 Hz, J _{1 ′ H,2 ′ Hb} = 2.9 Hz, 1 H, 2′H_b), 4.93-5.21 (br s, 2 H, 2 × OH, exch. D₂O), 7.48 (d, J _5H,6H = 8.1 Hz, 1 H, 5-H), 7.89 (d, J _5H,6H = 8.1 Hz, 1 H, 4-H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 64.5, 65.3, 73.7, 86.2, 105.9, 174.5. MS (FAB): m/z = 158 [M + H⁺]. Anal. Calcd for C₆H₇NO₄: C, 45.86; H, 4.49; N, 8.91. Found: C, 46.17; H, 4.58; N, 8.79.
Compound 4b: white solid; yield: 80%; mp 159-161 ˚C. IR (KBr): 3391, 3386, 3009, 1051 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 4.13 (dd, J _{2 ′ Ha,2 ′ Hb} = 10.1 Hz, J _{1 ′ H,2 ′ Ha} = 5.3 Hz, 1 H, 2′H_a), 4.29 (dd, J _{1 ′ H,2 ′ Ha} = 5.3 Hz, J _{1 ′ H,2 ′ Hb} = 2.9 Hz, 1 H, 1′H), 4.66 (dd, J _{2 ′ Ha,2 ′ Hb} = 10.1 Hz, J _{1 ′ H,2 ′ Hb} = 2.9 Hz, 1 H, 2′H_b), 4.93-5.25 (br s, 2 H, 2× OH, exch. D₂O), 7.47 (d, J _5H,6H = 8.2 Hz, 1 H, 5-H), 7.91 (d, J _5H,6H = 8.2 Hz, 1 H, 4-H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ= 64.2, 65.4, 73.3, 86.5, 105.7, 192.3. MS (FAB): m/z = 174 [M + H⁺]. Anal. Calcd for C₆H₇NO₃S: C, 41.61; H, 4.07; N, 8.09. Found: C, 41.86; H, 4.21; N, 7.88.
Compound 4c: white solid; yield: 79%; mp 153-155 ˚C. IR (KBr): 3399-3382, 3008, 1689 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 3.88 (ddd, J _{2 ′ H,3 ′ Ha} = 5.4 Hz, J _{1 ′ H,2 ′ H} = 4.6 Hz, J _{2 ′ H,3 ′ Hb} = 2.7 Hz, 1 H, 2′H), 4.03 (dd, J _{3 ′ Ha,3 ′ Hb} = 10.5 Hz, J _{2 ′ H,3 ′ Ha} = 5.4 Hz, 1 H, 3′H_a), 4.37 (d, J _{1 ′ H,2 ′ H} = 4.6 Hz, 1 H, 1′H), 4.59 (dd, J _{3 ′ Ha,3 ′ Hb} = 10.5 Hz, J _{2 ′ H,3 ′ Hb} = 2.7 Hz, 1 H, 3′H_b), 5.01-5.37 (br s, 3 H, 3 × OH, exch. D₂O), 7.51 (d, J _4H,5H = 8.1 Hz, 1 H, 5-H), 7.85 (d, J _4H,5H = 8.1 Hz, 1 H, 4-H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 64.3, 65.9, 71.7, 73.5, 86.5, 106.3, 174.8. MS (FAB): m/z = 188 [M + H⁺]. Anal. Calcd for C₇H₉NO₅: C, 44.92; H, 4.85; N, 7.48. Found: C, 44.69; H, 4.73; N, 7.73.
Compound 4d: white solid; yield: 85%; mp 141-142 ˚C. IR (KBr): 3398-3382, 3011, 1055 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 3.89 (ddd, J _{2 ′ H,3 ′ Ha} = 5.4 Hz, J _{1 ′ H,2 ′ H} = 4.7 Hz, J _{2 ′ H,3 ′ Hb} = 2.7 Hz, 1 H, 2′H), 4.06 (dd, J _{3 ′ Ha,3 ′ Hb} = 10.5 Hz, J _{2 ′ H,3 ′ Ha} = 5.4 Hz, 1 H, 3′H_a), 4.34 (d, J _{1 ′ H,2 ′ H} = 4.7 Hz, 1 H, 1′H), 4.63 (dd, J _{3 ′ Ha,3 ′ Hb} = 10.5 Hz, J _{2 ′ H,3 ′ Hb} = 2.7 Hz, 1 H, 3′H_b), 5.06-5.38 (br s, 3 H, 3 × OH, exch. D₂O), 7.54 (d, J _4H,5H = 8.1 Hz, 1 H, 5-H), 7.81 (d, J _4H,5H = 8.1 Hz, 1 H, 4-H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 64.7, 65.5, 71.5, 73.8, 86.7, 106.1, 192.7. MS (FAB): m/z = 204 [M + H⁺]. Anal. Calcd for C₇H₉NO₄S: C, 41.37; H, 4.46; N, 6.89. Found: C, 41.68; H, 4.31; N, 7.08.

20

General Procedure for the Synthesis of 4-Poly-hydroxyalkylquinolines 6: An intimate, solvent-free mixture of 1,3-oxazin-2-one(thione) 4 (2.4 mmol), cyclic ketone 5 (2.4 mmol) and montmorillonite K-10 clay (0.25 g) in a 20-mL vial was subjected to MW irradiation in a CEM Discover Focused Microwave Synthesis System at 90 ˚C for 9-14 min. After completion of the reaction as indicated by TLC, H₂O (10 mL) was added to precipitate the crude product, which was recrystallized from EtOH to give an analytically pure sample of 6 as a white solid.
Characterization Data of Representative Compounds: Compound 6a: white solid; yield: 91%; mp 187-189 ˚C. IR (KBr): 3393, 3003, 1598, 1579, 1457 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 2.13-2.32 (m, 4 H, 5-CH₂, 6-CH₂), 3.74 (dd, J _{2 ′ Ha,2 ′ Hb} = 10.5 Hz, J _{1 ′ H,2 ′ Ha} = 5.5 Hz, 1 H, 2′H_a), 4.18 (dd, J _{2 ′ Ha,2 ′ Hb} = 10.5 Hz, J _{1 ′ H,2 ′ Hb} = 2.9 Hz, 1 H, 2′H_b), 4.29 (dd, J _{1 ′ H,2 ′ Ha} = 5.5 Hz, J _{1 ′ H,2 ′ Hb} = 2.9 Hz, 1 H, 1′H), 4.99-5.13 (br s, 2 H, 2 × OH, exch. D₂O), 5.76 (m, 1 H, 7-H), 6.89 (d, J _7H,8H = 6.1 Hz, 1 H, 8-H), 7.92 (d, J _2H,3H = 7.7 Hz, 1 H, 2-H), 8.07 (d, J _2H,3H = 7.7 Hz, 1 H, 3-H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 23.9, 28.8, 64.1, 70.3, 121.9, 123.5, 130.5, 135.5, 144.8, 147.9, 153.1. MS (FAB): m/z = 192 [M + H⁺]. Anal. Calcd for C₁₁H₁₃NO₂: C, 69.09; H, 6.85; N, 7.32. Found: C, 69.45; H, 6.71; N, 7.65.
Compound 6b: white solid; yield: 83%; mp 176-178 ˚C. IR (KBr): 3380-3398, 3009, 1603, 1582, 1455 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 2.13-2.32 (m, 4 H, 5-CH₂, 6-CH₂), 3.85 (ddd, J _{2 ′ H,3 ′ Ha} = 5.3 Hz, J _{1 ′ H,2 ′ H} = 4.6 Hz, J _{2 ′ H,3 ′ Hb} = 2.8 Hz, 1 H, 2′H), 4.05 (dd, J _{3 ′ Ha,3 ′ Hb} = 10.3 Hz, J _{2 ′ H,3 ′ Ha} = 5.3 Hz, 1 H, 3′H_a), 4.29 (d, J _{1 ′ H,2 ′ H} = 4.7 Hz, 1 H, 1′H), 4.56 (dd, J _{3 ′ Ha,3 ′ Hb} = 10.3 Hz, J _{2 ′ H,3 ′ Hb} = 2.8 Hz, 1 H, 3′H_b), 4.99-5.16 (br s, 3 H, 3 × OH, exch. D₂O), 5.78 (m, 1 H, 7-H), 6.85 (d, J _7H,8H = 6.2 Hz, 1 H, 8-H), 7.95 (d, J _2H,3H = 7.7 Hz, 1 H, 2-H), 8.08 (d, J _2H,3H = 7.7 Hz, 1 H, 3-H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 23.8, 28.9, 64.5, 70.1, 73.5, 121.7, 123.8, 130.1, 135.5, 144.9, 147.6, 153.2. MS (FAB): m/z = 222 [M + H⁺]. Anal. Calcd for C₁₂H₁₅NO₃: C, 65.14; H, 6.83; N, 6.33. Found: C, 64.86; H, 6.61; N, 6.55.
Compound 6e: white solid; yield: 89%; mp 203-205 ˚C. IR (KBr): 3395, 2998, 1693, 1601, 1585, 1451 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 2.18 (m, 2 H, 6-CH₂), 2.67 (t, J _5H,6H = 6.3 Hz, 2 H, 5-CH₂), 2.91 (t, J _6H,7H = 5.8 Hz, 2 H,
7-CH₂), 3.71 (dd, J _{2 ′ Ha,2 ′ Hb} = 10.5 Hz, J _{1 ′ H,2 ′ Ha} = 5.5 Hz, 1 H, 2′H_a), 4.12 (dd, J _{2 ′ Ha,2 ′ Hb} = 10.5 Hz, J _{1 ′ H,2 ′ Hb} = 2.7 Hz, 1 H, 2′H_b), 4.23 (dd, J _{1 ′ H,2 ′ Ha} = 5.5 Hz, J _{1 ′ H,2 ′ Hb} = 2.7 Hz, 1 H, 1′H), 5.03-5.19 (br s, 2 H, 2 × OH, exch. D₂O), 7.89 (d, J _2H,3H = 7.6 Hz, 1 H, 2-H), 8.03 (d, J _2H,3H = 7.6 Hz, 1 H, 3-H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 23.7, 25.2, 44.1, 63.5, 70.5, 129.5, 131.7, 145.9, 148.3, 155.1, 192.5. MS (FAB): m/z = 208 [M + H⁺]. Anal. Calcd for C₁₁H₁₃NO₃: C, 63.76; H, 6.32; N, 6.76. Found: C, 63.49; H, 6.61; N, 6.93.
Compound 6g: white solid; yield: 91%; mp 196-198 ˚C. IR (KBr): 3393, 2998, 1695, 1605, 1581, 1458 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 2.21 (m, 2 H, 7-CH₂), 2.66 (t, J _7H,8H = 6.3 Hz, 2 H, 8-CH₂), 2.92 (t, J _6H,7H = 5.7 Hz, 2 H, 6-CH₂), 3.74 (dd, J _{2 ′ Ha,2 ′ Hb} = 10.5 Hz, J _{1 ′ H,2 ′ Ha} = 5.3 Hz, 1 H, 2′H_a), 4.11 (dd, J _{2 ′ Ha,2 ′ Hb} = 10.5 Hz, J _{1 ′ H,2 ′ Hb} = 2.7 Hz, 1 H, 2′H_b), 4.28 (dd, J _{1 ′ H,2 ′ Ha} = 5.3 Hz, J _{1 ′ H,2 ′ Hb} = 2.7 Hz, 1 H, 1′H), 5.07-5.18 (br s, 2 H, 2 × OH, exch. D₂O), 7.85 (d, J _2H,3H = 7.5 Hz, 1 H, 2-H), 8.04 (d, J _2H,3H = 7.5 Hz, 1 H, 3-H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 23.9, 25.1, 44.6, 63.1, 70.8, 129.3, 131.7, 145.5, 148.3, 155.2, 192.3. MS (FAB): m/z = 208 [M + H⁺]. Anal. Calcd for C₁₁H₁₃NO₃: C, 63.76; H, 6.32; N, 6.76. Found: C, 63.93; H, 6.51; N, 6.59.