Practical and Novel One-Pot
Protocol for the Synthesis of Highly Functionalized Pyridinols
and Pyrido[1,2-a]-Fused
1,3-Diazaheterocycles

Abdolali Alizadeh; Atieh Rezvanian

doi:10.1055/s-0030-1259942

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Synlett 2011(8): 1105-1108
DOI: 10.1055/s-0030-1259942

LETTER

Practical and Novel One-Pot Protocol for the Synthesis of Highly Functionalized Pyridinols and Pyrido[1,2-a]-Fused 1,3-Diazaheterocycles

Abdolali Alizadeh*, Atieh Rezvanian
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran 18716, Iran
Fax: +98(21)88006544; e-Mail: abdol_alizad@yahoo.com; e-Mail: aalizadeh@modares.ac.ir;

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Publikationsverlauf

Received 23 December 2010
Publikationsdatum:
07. April 2011 (online)

Abstract
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Abstract

A novel and efficient protocol for the generation of substituted pyridinols and pyrido[1,2-a]-fused 1,3-diazaheterocycles from primary amine or 1,n-diamine, nitro ketene dithioacetal [1,l-bis(methylthio)-2-nitroethene] and dibenzylideneacetone as starting materials in a one-pot process combining a Michael addition reaction and nucleophilic addition under mild condition in high yield has been developed.

Key words

pyridinol - pyrido[1,2-a]-fused 1,3-diazaheterocycle - Michael addition reaction - 1,n-diamine - nitro ketene dithioacetal - 1,l-bis(methylthio)-2-nitroethene - dibenzylideneacetone

References and Notes

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35

A solution of l,l-bis(methylthio)-2-nitroethene (0.165 g, 1 mmol) and 1,2-ethanediamine (0.06 g, 1 mmol) in MeCN (5 mL) was magnetically stirred for 4 h at reflux. Then a solution of dibenzylideneacetone (0.23 g, 1 mmol) in MeCN (3 mL) was added and the mixture was stirred for 4 h. After completion of the reaction, the mixture was filtered and the precipitate was washed with cold MeCN (4 mL) to afford the pure product 3a as a white powder; mp 225 ˚C (dec.), yield: 0.276 g, 76%. IR (KBr): 3294 (OH), 3114 (NH), 1607 (NC=C), 1590, 1578, 1522 (Ph), 1569, 1396 (CNO₂) cm^-¹. Major isomer 3a: ^¹H NMR (500.1 MHz, CDCl₃): δ = 2.62-2.64 (2 H, m, CH₂ of ring), 3.31-3.35 (2 H, m, CH₂NH), 3.54-3.58 (2 H, m, CH₂N), 4.37-4.38 (1 H, m, CH), 6.31 (1 H, s, OH), 6.91 (1 H, d, ^³ J _H,H = 14.1 Hz, CH=CHPh), 6.99 (1 H, d, ^³ J _H,H = 14.1 Hz, CH=CHPh), 7.01-7.21 (10 ¥ H, m, 10 CH of Ph), 9.19 (1 H, s, NH). ^¹³C NMR (125.7 MHz, CDCl₃): δ = 30.95 (CCHPh), 37.66 (CH₂), 43.50 (CH₂NH), 46.63 (CH₂N), 96.13 (COH), 108.42 (CNO₂), 126.03 (CH of Ph), 126.46 (2 ¥ CH of Ph), 127.15 (2 ¥ CH of Ph), 128.29 (2 ¥ CH of Ph), 128.34 (2 ¥ CH of Ph), 129.33 (C=CPh), 131.27 (C=CPh), 131.84 (CH of Ph), 133.24 (C_ipso of Ph), 143.14 (C_ipso of Ph), 152.41 (NHCN). Minor isomer 3a: ^¹H NMR (500.1 MHz, CDCl₃): δ = 2.54-2.59 (2 H, m, CH₂ of ring), 3.36-3.43 (2 H, m, CH₂NH), 3.62-3.67 (2 H, m, CH₂N), 4.29-4.31 (1 H, m, CH), 6.32 (1 H, s, OH), 6.90 (1 H, d, ^³ J _H,H = 14.1 Hz, CH=CHPh), 6.98 (1 H, d, ^³ J _H,H = 14.1 Hz, CH=CHPh), 7.31-7.76 (10 H, m, 10 ¥ CH of Ph), 9.18 (1 H, s, NH). ^¹³C NMR (125.7 MHz, CDCl₃): δ = 30.92 (CH), 37.33 (CH₂), 43.14 (CH₂NH), 46.59 (CH₂N), 96.11 (COH), 108.46 (CNO₂), 126.11 (CH of Ph), 126.54 (2 ¥ CH of Ph), 127.61 (2 ¥ CH of Ph), 128.36 (2 ¥ CH of Ph), 128.39 (2 ¥ CH of Ph), 129.47 (C=CPh), 131.46 (C=CPh), 131.99 (CH of Ph), 133.85 (C_ipso of Ph), 143.20 (C_ipso of Ph), 152.44 (NHCN). MS: m/z (%) = 363 (5) [M]⁺, 286 (9), 260 (4), 230 (11), 177 (23), 77 (100). Anal. Calcd for C₂₁H₂₁N₃O₃ (363.41): C, 69.41; H, 5.82; N, 11.56. Found: C, 69.46; H, 5.79; N, 11.54. Compound 3b: white powder; mp 240 ˚C (dec.); yield: 0.308 g, 82%. IR (KBr): 3231 (OH), 3063 (NH), 1609 (NC=C), 1590, 1578, 1524 (Ph), 1561, 1399 (CNO₂) cm^-¹. Major isomer 3b: ^¹H NMR (500.1 MHz, CDCl₃): δ = 1.83-1.86 (2 H, m, CH₂), 2.37-2.39 (2 H, m, CH₂ of ring), 3.40-3.47 (4 H, m, CH₂NH, CH₂N), 4.44-4.48 (1 H, m, CH), 5.55 (1 H, d, ^³ J _H,H = 15.4 Hz, CH=CHPh), 6.55 (1 H, d, ^³ J _H,H = 15.4 Hz, CH=CHPh), 6.93 (1 H, s, OH), 7.11-7.23 (10 H, m, 10 ¥ CH of Ph), 11.87 (1 H, s, NH). ^¹³C NMR (125.7 MHz, CDCl₃): δ = 20.02 (CH₂), 37.53 (CH), 38.74 (CH₂NH), 38.86 (CH₂N), 43.85 (CH₂), 85.15 (COH), 107.24 (CNO₂), 126.13 (CH of Ph), 126.88 (2 ¥ CH of Ph), 127.20 (2 ¥ CH of Ph), 128.70 (2 ¥ CH of Ph), 128.80 (2 ¥ CH of Ph), 129.11 (C=CPh), 130.00 (C=CPh), 131.28 (CH of Ph), 136.28 (C_ipso of Ph), 143.69 (C_ipso of Ph), 153.31 (NHCN). Minor isomer 3b: ^¹H NMR (500.1 MHz, CDCl₃): δ = 2.02-2.08 (2 H, m, CH₂), 2.47-2.52 (2 H, m, CH₂), 3.15-3.25 (4 H, m, CH₂NH, CH₂N), 4.10-4.18 (1 H, m, CH), 6.34 (1 H, d, ^³ J _H,H = 15.4 Hz, CH=CHPh), 6.63 (1 H, d, ^³ J _H,H = 15.4 Hz, CH=CHPh), 6.88 (1 H, s, OH), 7.34-7.71 (10 H, m, 10 ¥ CH of Ph), 11.87 (1 H, s, NH). ^¹³C NMR (125.7 MHz, CDCl₃): δ = 19.29 (CH₂), (CH), 36.19 (CH₂NH), 38.74 (CH₂N), 44.12 (CH₂), 85.27 (COH), 107.65 (CNO₂), 125.75 (CH of Ph), 127.80 (2 ¥ CH of Ph), 127.99 (2 ¥ CH of Ph), 128.54 (2 ¥ CH of Ph), 128.83 (2 ¥ CH of Ph), 129.42 (C=CPh), 130.54 (C=CPh), 131.87 (CH of Ph), 136.21 (C_ipso of Ph), 145,49 (C_ipso of Ph), 153.65 (NHCN). MS: m/z (%) = 358 (2) [M - 1 - H₂O]⁺, 357 (2) [M - 2 - H₂O]⁺, 331 (3), 302 (3), 256 (2), 234 (100), 233 (87), 131 (46), 103 (65), 91 (34), 77 (59). Anal. Calcd for C₂₂H₂₃N₃O₃ (377.45): C, 70.01; H, 6.14; N, 11.13. Found: C, 70.11; H, 6.09; N, 11.15.
Compound 3c: white powder; mp 234 ˚C (dec.); yield: 0.30 g, 75%. IR (KBr): 3270 (OH), 3100 (NH), 1609 (NC=C), 1592, 1570, 1528 (Ph), 1573, 1391 (CNO₂) cm^-¹. Major isomer 3c: ^¹H NMR (500.1 MHz, CDCl₃): δ = 0.97 (3 H, s, Me), 1.00 (3 H, s, Me), 2.45-2.49 (2 H, m, CH₂ of ring), 3.06-3.17 (4 H, m, CH₂NH, CH₂N), 4.49-4.53 (1 H, m, CH), 5.42 (1 H, d, ^³ J _H,H = 15.1 Hz, CH=CHPh), 6.53 (1 H, d, ^³ J _H,H = 15.1 Hz, CH=CHPh), 6.85 (1 H, s, OH), 7.01-7.27 (10 H, m, 10 ¥ CH of Ph), 11.86 (1 H, s, NH). ^¹³C NMR (125.7 MHz, CDCl₃): δ = 23.69 (Me), 24.33 (Me), 26.43 (CH), 37.35 (CH), 43.66 (CH₂), 49.83 (CH₂NH), 50.96 (CH₂N), 85.09 (COH), 106.74 (CNO₂), 125.79 (CH of Ph), 126.31 (2 ¥ CH of Ph), 127.53 (2 ¥ CH of Ph), 128.76 (2 ¥ CH of Ph), 128.84 (2 ¥ CH of Ph), 129.39 (C=CPh), 130.55 (C=CPh), 131.04 (CH of Ph), 136.22 (C_ipso of Ph), 143.55 (C_ipso of Ph), 152.14 (NHCN). Minor isomer 3c: ^¹H NMR (500.1 MHz, CDCl₃): δ = 0.88 (3 H, s, Me), 1.90 (3 H, s, Me), 2.31-2.36 (2 H, m, CH₂ of ring), 3.37-3.42 (4 H, m, CH₂NH, CH₂N), 4.19-4.24 (1 H, m, CH), 6.34 (1 H, d, ^³ J _H,H = 15.1 Hz, CH=CHPh), 6.71 (1 H, d, ^³ J _H,H = 15.1 Hz, CH=CHPh), 6.88 (1 H, s, OH), 7.33-7.70 (10 H, m, 10 ¥ CH of Ph), 11.81 (1 H, s, NH). ^¹³C NMR (125.7 MHz, CDCl₃): δ = 23.97 (Me), 24.04 (Me), 26.60 (CH), 38.55 (CH), 43.97 (CH₂), 50.21 (CH₂NH), 51.23 (CH₂N), 85.01 (COH), 107.41 (CNO₂), 126.04 (CH of Ph), 126.90 (2 ¥ CH of Ph), 127.14 (2 ¥ CH of Ph), 128.29 (2 ¥ CH of Ph), 129.14 (2 ¥ CH of Ph), 129.87 (C=CPh), 130.67 (C=CPh), 131.16 (CH of Ph), 136.10 (C_ipso of Ph), 145.42 (C_ipso of Ph), 152.63 (NHCN). MS: m/z (%) = 407 (2) [M + 2]⁺, 329 (3), 255 (9), 234 (11), 171 (49), 141 (11), 125 (100), 91 (12), 84 (50). Anal. Calcd for C₂₄H₂₇N₃O₃ (405.50): C, 71.09; H, 6.71; N, 10.36. Found: C, 71.02; H, 6.76; N, 10.32.