References
- 1
Lainton JAH.
Huffman JW.
Martin BR.
Compton DR.
Tetrahedron Lett.
1995,
36:
1401
-
2a
Huffman JW.
Dai D.
Martin BR.
Compton DR.
Bioorg. Med. Chem. Lett.
1994,
4:
563
-
2b
Wiley JL.
Compton DR.
Dai D.
Lainton JAH.
Phillips M.
Huffman JW.
Martin BR.
J. Pharmacol. Exp. Ther.
1998,
278:
995
-
2c
Huffman JW.
Curr. Med. Chem.
1999,
6:
705
-
3a
Reggio PH.
Basu-Dutt S.
Barnett-Norris J.
Castro MT.
Hurst DP.
Seltzman JJ.
Roche MJ.
Gilliam AF.
Thomas BF.
Stevenson LA.
Pertwee RG.
Abood ME.
J. Med. Chem.
1998,
41:
5177
-
3b
Huffman JW.
Mabon R.
Wu M.-J.
Lu J.
Hart R.
Hurst DP.
Reggio PH.
Wiley JL.
Martin BR.
Bioorg. Med. Chem.
2003,
11:
539
- 4
Apsimon JW.
Durham DG.
Rees AH.
J. Chem. Soc., Perkin Trans. 1
1978,
1588
- 5
Thompson TW. J. Chem. Soc., Chem. Commun.
1968,
532
- 6
Sukawa H.
Seshimoto O.
Tezuka T.
Mukai T.
J. Chem. Soc., Chem. Commun.
1974,
696
- 7
Boukou-Poba JP.
Farnier M.
Guilard R.
Tetrahedron Lett.
1979,
19:
1717
- 8
Katritzky AR.
Li J.
Gordeev MF.
Synthesis
1994,
93
- 9
Severin T.
Poehlmann H.
Chem. Ber.
1977,
110:
491
- 10
Ellames GJ.
Hewkin CT.
Jackson RFW.
Smith DI.
Standen SP.
Tetrahedron Lett.
1989,
26:
3471
- 11
Dhanak D.
Reese CB.
Romana S.
Zappia G.
J. Chem. Soc., Chem. Commun.
1986,
903
- 12
Korostova SE.
Mikhaleva AI.
Sobenina LN.
Shevchenko SG.
Polovnikova RI.
J. Org. Chem. USSR
1986,
436
- 13
Xu Z.
Lu X.
J. Org. Chem.
1999,
63:
5031
- 14
Johnson CN.
Stemp G.
Anand N.
Stephen SC.
Gallagher T.
Synlett
1998,
1025
- 15
Thoresen LH.
Kim H.
Welch MB.
Burghart A.
Burgess K.
Synlett
1998,
1276
- 16
Martina S.
Enkelmann V.
Wegner G.
Schluter A.-D.
Synthesis
1991,
613
- 17
Grieb JG.
Ketcha DM.
Synth. Commun.
1995,
25:
2145
- 18
Chen W.
Stephenson EK.
Cava MP.
Jackson YA.
Org. Synth.
1991,
70:
151
- 19
Rokach J.
Hamel P.
Kakushima M.
Smith GM.
Tetrahedron Lett.
1981,
22:
4901
- 20
Groenendaal L.
Van Loo JAJM.
Meijer EW.
Synth. Commun.
1995,
25:
1589
-
21a
Koike T.
Shinohara Y.
Nishimura T.
Hagiwara M.
Tobinaga S.
Takeuchi N.
Heterocycles
2000,
53:
1351
-
21b
Although the 1H NMR data reported by these authors agree with ours, these authors report a mp of 122-123 °C, while in several preparations of 2, we find a mp of 105-106 °C (see ref.
[23]
).
- 22
Knight LW.
Padgett CW.
Huffman JW.
Pennington WT.
Acta Crystallogr., Sect. E
2003,
59:
762
- 24
Miyaura N.
Yanagi T.
Suzuki A.
Synth. Commun.
1981,
11:
513
- 27
Laatsch H.
Pudleiner H.
Liebigs Ann. Chem.
1989,
863
23
Experimental Procedure for the Preparation of 2. To a solution of 3.1 mL of 1 (44.7 mmol) in 120 mL of freshly distilled THF in a flame-dried flask under N2 at -78 °C was added 6.53 g (22.4 mmol) of 1,3-dibromo-5,5-dimethyl-hydantoin. The mixture was stirred for 30 min and allowed to stand for an additional 3.5 h under ambient room light at -78 °C. To this solution were added 4 mL of Bu3N and 180 mL of freshly distilled Et2O and the mixture was stirred for 10 min at -78 °C. The resulting gray precipitate was removed by filtration(vacuum) and the solution was concentrated in vacuo to remove the Et2O. To this solution was added 17.04 g (89.4 mmol) of p-toluenesulfonyl chloride and the inert atmosphere was reestablished. The solution was cooled to 0 °C and 5.36 g (134.0 mmol) of NaH (60% in mineral oil) was added cautiously. The mixture was stirred for 18 h at ambient temperature and 60 mL of H2O were added. The mixture was extracted with Et2O and the ether extracts were washed with successive portions of 1 M HCl and sat. aq NaHCO3. This mixture was combined with an equal volume of 2 M NaOH and was stirred for 2 h at r.t. The layers were separated and the organic extract was washed repeatedly with H2O and 2 M NaOH. The organic layer was dried (MgSO4) and concentrated in vacuo to give a light brown solid. Recrystallization from isopropyl alcohol gave 10.73 g (80%) of 2-bromo-1-(p-toluenesulfonyl)pyr-role as a white crystalline solid: mp 105-106 °C. 1H NMR (300 MHz, CDCl3): δ = 2.43 (s, 3 H), 6.23-6.29 (m, 2 H), 7.32 (d, J = 8.3 Hz, 2 H), 7.46 (dd, J = 2.0, 3.5 Hz, 1 H), 7.81 (d, J = 8.4 Hz, 2 H). 13C NMR (75.5 MHz, CDCl3): δ = 145.5, 135.1, 129.9, 127.8, 124.2, 117.9, 113.5, 112.5, 100.0, 21.7. MS (EI): m/z (%) = 301 (27), 299 (28), 155 (56), 91 (100). Anal. Calcd for C11H10BrNO2S: C, 44.02; H, 3.36; N, 4.67. Found: C, 44.65; H, 3.36; N, 4.67. Although this compound is homogeneous to TLC, GC/MS, 1H and 13C NMR, aceptable analytical data could not be obtained.
25
Experimental Procedure for the Preparation of 4 (Ar = 4-Methoxyphenyl). A mixture of 0.020 g (0.02 mmol) of Pd(PPh3)4 and 4.4 mL of distilled toluene was stirred under an inert atmosphere for 5 min at ambient temperature, and 0.470 g (1.6 mmol) of 2-bromo-N-p-toluenesulfonylpyrrole was added as a solid, followed by 0.256 g (2.4 mmol) of Na2CO3 in 2.2 ml of H2O. To this mixture was added 0.250 g (1.6 mmol) of 4-methoxy-phenylboronic acid in 3 mL of 95% EtOH. The mixture was heated at reflux for 6 h, cooled to ambient temperature, and extracted into EtOAc. The combined organic extracts were washed with brine, dried (MgSO4), and concentrated in vacuo to give a brown solid. Recrystallization from 2-propanol gave 0.412 g (80%) of 2-(4-methoxyphenyl)-N-tosylpyrrole as a white crystalline solid: mp 120-121 °C. 1H NMR (300 MHz, CDCl3): δ = 2.34 (s, 3 H), 3.84 (s, 3 H), 6.10 (dd, J = 1.8, 3.0 Hz, 1 H), 6.28 (t, J = 3.4 Hz, 1 H), 6.81-6.86 (m, 2 H), 7.09-7.17 (m, 4 H), 7.25-7.26 (m, 2 H), 7.41 (dd, J = 1.8, 3.1 Hz, 1 H). 13C NMR (75.5 MHz, CDCl3): δ = 21.5, 55.2, 111.9, 112.7, 115.3, 123.7, 127.1, 129.3, 132.2. MS (EI): m/z (%) = 327 (17), 172 (100). Anal. Calcd for C18H17NO3S: C, 66.03; H, 5.23; N, 4.28. Found: C, 66.27; H, 5.31; N, 4.31.
Compound 3 (Ar = Phenyl): mp 123-124 °C. 1H NMR (300 MHz, CDCl3): δ = 2.35 (s, 3 H), 6.15 (dd, J = 1.7, 3.2 Hz, 1 H), 6.30 (t, J = 3.3 Hz, 1 H), 7.09 (d, J = 8.3 Hz, 2 H), 7.21-7.38 (m, 7 H), 7.44 (dd, J = 1.7, 3.3 Hz, 1 H). 13C NMR (75.5 MHz, CDCl3): δ = 21.6, 112.0, 115.7, 124.1, 127.1, 127.3, 128.2, 129.3, 130.9, 131.4, 135.6, 136.0, 144.6. MS (EI): m/z (%) = 297 (38), 142 (100). Anal. Calcd for C17H15NO2S: C, 68.66; H, 5.08, N, 4.71. Found: C, 68.39; H, 5.03, N, 4.56.
Compound 3 (Ar = 4-Methylphenyl): mp 120-121 °C. 1H NMR (300 MHz, CDCl3): δ = 2.34 (s, 3 H), 2.39 (s, 3 H), 6.11 (dd, J = 1.7, 3.2 Hz, 1 H), 6.28 (t, J = 3.3 Hz, 1 H), 7.06-7.12 (m, 6 H), 7.24-7.16 (m, 2 H), 7.41 (dd, J = 1.8, 3.3 Hz, 1 H). 13C NMR (75.5 MHz, CDCl3): δ = 21.3, 21.5, 112.0, 115.5, 123.9, 127.0, 128.0, 128.5, 129.3, 130.7, 135.7, 136.1, 138.0, 144.5. MS (EI): m/z (%) = 311 (40), 156 (100). Anal. Calcd for C18H17NO2S: C, 69.43; H, 5.50, N, 4.50. Found: C, 69.69; H, 5.51, N, 4.42.
Compound 3 (Ar = 3-Chlorophenyl): mp 91-92 °C. 1H NMR (300 MHz, CDCl3): δ = 2.37 (s, 3 H), 6.16-6.17 (m, 1 H), 6.30 (t, J = 3.2 Hz, 1 H), 7.04-7.34 (m, 8 H), 7.45-7.46 (m, 1 H). 13C NMR (75.5 MHz, CDCl3): δ = 21.5, 111.9, 116.1, 124.4, 127.0, 128.2, 128.7, 129.2, 129.4, 130.6, 133.1, 134.1, 135.4, 145.0. MS (EI): m/z (%) = 331 (37), 176 (100). Anal. Calcd for C17H14ClNO2S: C, 61.53; H, 4.25; N, 4.22. Found: C, 61.25; H, 4.34; N, 4.25.
Compound 3 (Ar = 1-Naphthyl): mp 146-147 °C. 1H NMR (300 MHz, CDCl3): δ = 2.18 (s, 3 H), 6.26 (dd, J = 1.7, 2.2 Hz, 1 H), 6.41 (t, J = 3.3 Hz, 1 H), 6.79 (d, J = 8, 2 Hz, 2 H), 7.03 (d, J = 8.3 Hz, 2 H), 7.09-7.26 (m, 2 H), 7.33-7.44 (m, 3 H), 7.59 (dd, J = 1.7, 3.3 Hz, 1 H), 7.77 (d, J = 8.2 Hz, 1 H), 7.86 (d, J = 8.2 Hz, 1 H). 13C NMR (75.5 MHz, CDCl3): δ = 21.3, 111.0, 116.5, 122.8, 124.4, 125.3, 125.8, 127.2, 127.6, 128.6, 129.0, 129.1, 130.5, 131.9, 132.9, 133.7, 135.0, 144.4. MS (EI): m/z (%) = 347(34), 192(100); Anal. Calcd for C21H17NO2S: C, 72.60; H, 4.93; N, 4.03. Found: C, 72.36; H, 4.96; N, 3.99.
Compound 3 (Ar = 3-Nitrophenyl): pale pink gum. 1H NMR (300 MHz, CDCl3): δ = 2.36 (s, 3 H), 6.27 (dd, J = 1.7, 3.1 Hz, 1 H), 6.36 (t, J = 3.3 Hz, 1 H), 7.14 (d, J = 8.3 Hz, 2 H), 7.25 (d, J = 8.4 Hz, 2 H), 7.49 (dd, J = 1.6, 3.9 Hz, 1 H), 7.53 (d, J = 7.9 Hz, 1 H), 7.68 (dt, J = 1.3, 7.7 Hz, 1 H), 7.94 (t, J = 1.9 Hz, 1 H), 8.18-8.22 (m, 1 H). 13C NMR (75.5 MHz, CDCl3): δ = 21.5, 112.4, 117.1, 122.9, 125.0, 125.1, 126.8, 128.3, 129.6, 133.0, 135.3, 136.9, 145.3, 147.3. MS (EI): m/z (%) = 342 (100), 203 (26). HRMS calcd for C17H14N2O4S: 342.0674. Found: 342.0670.
26 A mixture of 0.050 g (0.15 mmol) of 2-(4-methoxyphenyl)-N-tosylpyrrole in 0.6 mL of EtOH and 0.2 mL of 15% ethanolic NaOH was stirred at reflux temperature for 3 h. The solution was concentrated in vacuo; the residue was dissolved in CH2Cl2 and washed with H2O. The organic layer was dried (MgSO4) and concentrated in vacuo to give 0.025 g (97%) of 2-(4-methoxyphenyl)pyrrole as a white solid: mp 143-144 °C (lit. mp 147 °C27). 1H NMR (300 MHz, CDCl3): δ = 3.81 (s, 3 H), 6.27 (dd, J = 2.8, 5.7 Hz, 1 H), 6.40 (t, J = 3.5 Hz, 1 H), 6.79 (dd, J = 2.4, 3.9 Hz, 1 H), 6.88-6.91 (m, 2 H), 7.36-7.39 (m, 2 H), 8.32 (br s, 1 H). 13C NMR (75.5 MHz, CDCl3): δ = 55.3, 104.8, 109.9, 114.3, 118.1, 125.2, 125.9, 132.1, 158.2. MS (EI): m/z (%) = 245 (7), 173 (70), 158 (100). The spectroscopic data agree with those reported previously.
[27]