P. Wyre˛bek et al. / Tetrahedron 65 (2009) 1268–1275
1273
128.8, 128.6, 126.9, 120.2, 84.8, 83.4, 64.8, 28.2, 21.5. Anal. Calcd for
C17H15N3: C, 78.13; H, 5.79. Found: C, 78.48; H, 5.72.
ether; 8.8ꢁ10ꢂ5 M) 244 (17 000), 255 (15 000). NMR (CDCl3): 1H
7.35 (d, 2H, J¼8.1 Hz), 7.10 (d, 2H, J¼8.1 Hz), 3.50 (dt, 1H, J¼8.8,
3.5 Hz), 3.08 (td, 1H, J¼5.6, 3.5 Hz), 2.34 (s, 3H), 2.05–1.29 (m, 8H);
13C 138.0, 131.6, 129.1, 120.5, 88.4, 84.2, 61.2, 34.8, 29.8, 28.0, 23.3,
22.2, 21.6. Anal. Calcd for C15H17N3: C, 75.28; H, 7.16. Found: C,
75.20; H, 7.24.
4.4.2. 1-(4-Fluorophenyl)-4-(4-methylphenyl)but-3-yn-1-yl
azide (2b)
Light-yellow oil. IR (cmꢂ1, neat) 3323 w, 3034 m, 2923 m, 2481
w, 2102 s, 1604 s, 1506 s, 1229 s, 1157 s, 833 s, 816 s. UV–vis (3,
M
ꢂ1 cmꢂ1; ether; 5.4ꢁ10ꢂ5 M) 245 (29 000), 256 (27 000). NMR
4.5.2. cis-2-Pent-1-yn-1-ylcyclohexyl azide (2g)
(CDCl3): 1H 7.38 (dd, 2H, J¼8.6, 5.427 Hz), 7.26 (d, 2H, J¼8.2 Hz), 7.10
(d, 2H, J¼8.2 Hz), 7.10 (dd/apparent t, 2H, J¼8.6, 8.627 Hz), 4.74 (t,
1H, J¼6.8 Hz), 2.90 (ABX, 1H, J¼16.9, 7.1 Hz), 2.83 (ABX, 1H, J¼16.9,
6.5 Hz), 2.34 (s, 3H); 13C 162.8 (d, J¼247.3 Hz), 138.3, 134.5, 131.6,
129.2, 128.7 (d, J¼8.2 Hz), 120.1, 115.8 (d, J¼21.6 Hz), 84.4, 83.7, 64.1,
28.3, 21.6. Anal. Calcd for C17H14FN3: C, 73.10; H, 5.05. Found: C,
73.40; H, 5.11.
Colorless oil. IR (cmꢂ1, neat) 3320 w, 2937 s, 2859 s, 2510 w,
2097 s, 1444 s, 1261 s, 1000 m. NMR (CDCl3): 1H 3.39 (dt, 1H, J¼8.8,
3.6 Hz), 2.89–2.76 (m, 1H), 2.17 (td, 2H, J¼7.0, 2.0 Hz), 1.98–1.20 (m,
10H), 0.98 (t, 3H, J¼7.3 Hz); 13C 84.1, 79.4, 61.4, 34.0, 30.1, 27.9, 23.4,
22.4, 22.1, 20.9, 13.6. Anal. calcd for C11H17N3: C, 69.07; H, 8.96.
Found: C, 69.34; H, 9.19.
4.5.3. 1-(3-Phenylprop-2-yn-1-yl)pentyl azide (2h)
4.4.3. 1-(4-Chlorophenyl)-4-(4-methylphenyl)but-3-yn-1-yl
azide (2c)
Light-yellow oil. IR (cmꢂ1, neat) 3340 w, 2963 s, 2934 s, 2862 s,
2502 w, 2099 s, 1596 m, 1486 s, 1338 s, 1258 s, 1071 m, 750 s, 690 s.
White solid, mp 40–41 ꢀC. IR (cmꢂ1, KBr) 2116 m, 1510 s, 1492 s,
UV–vis
(3,
M
ꢂ1 cmꢂ1
;
ether; 7.0ꢁ10ꢂ5 M) 241 (19 000), 252
1270 s, 1091 s, 814 s. UV–vis (
3
, Mꢂ1 cmꢂ1; ether; 4.4ꢁ10ꢂ5 M) 228
(18 000). NMR (CDCl3): 1H 7.48–7.38 (m, 2H), 7.37–7.27 (m, 3H),
3.66–3.46 (m, 1H), 2.70 (d, 2H, J¼6.0 Hz), 1.85–1.27 (m, 6H), 0.97 (t,
3H, J¼7.0 Hz); 13C 131.7, 128.4, 128.1, 123.5, 85.6, 83.1, 61.4, 33.5,
28.3, 26.0, 22.6, 14.1. Anal. Calcd for C14H17N3: C, 73.98; H, 7.54.
Found: C, 74.03; H, 7.65.
(18 000), 245 (26 000), 256 (24 000). NMR (CDCl3): 1H 7.38 (AB, 2H,
J¼8.7 Hz), 7.34 (AB, 2H, J¼8.7 Hz), 7.26 (d, 2H, J¼8.0 Hz), 7.10 (d, 2H,
J¼8.0 Hz), 4.73 (t, 1H, J¼6.8 Hz), 2.89 (ABX, 1H, J¼16.8, 7.1 Hz), 2.83
(ABX, 1H, J¼16.8, 6.5 Hz), 2.34 (s, 3H); 13C 138.4, 137.2, 134.5, 131.6,
129.2, 129.1, 128.4, 120.0, 84.2, 83.7, 64.1, 28.2, 21.6. Anal. Calcd for
C17H14ClN3: C, 69.03; H, 4.77. Found: C, 69.13; H, 4.59.
4.6. General procedure for the synthesis of pyrroles 3a–h
(microwave)
4.4.4. 4-Cyclopropyl-1-phenylbut-3-yn-1-yl azide (2d)
Light-yellow oil. IR (cmꢂ1, neat) 2973 s, 2864 s, 2100 s, 1382 s,
A 5 mL microwave reactor vial, equipped with a magnetic stir-
ring bar and fitted with a rubber septum, was charged with azide 2
(1.00 mmol) and 1,2-dichloroethane (2 mL). Zinc chloride (1.0 M in
ether; for 2a–d 0.20 mL, 0.20 mmol, for 2e 0.05 mL, 0.05 mmol, for
2e,f–h 0.40 mL, 0.40 mmol) was added dropwise with a syringe and
the vial was capped. The reaction was carried out with the fol-
lowing microwave reactor parameters: temperature 105 ꢀC, run
time 60 min (130 ꢀC, 40 min for 2e,f–h), power high (pressure ca.
2 bar). Silica gel column chromatography (10ꢁ2 cm; hexanes/ethyl
acetate 100:0/20:1) gave 3a (0.210 g, 90%), 3b (0.183 g, 73%), 3c
(0.244 g, 91%), 3d (0.140 g, 76%), 3e (0.142 g, 64%), 3e0 (0.073 g, 32%),
3f (0.110 g, 52%), 3g (0.067 g, 41%), and 3h (0.095 g, 48%).
1153 s, 113 s. UV–vis (
3
, Mꢂ1 cmꢂ1; ether; 8.5ꢁ10ꢂ5 M) 216 (28 000).
NMR (CDCl3): 1H 7.48–7.25 (m, 5H), 4.62 (t, 1H, J¼6.9 Hz), 2.65
(dABX, 1H, J¼16.8, 7.9, 1.9 Hz), 2.60 (dABX, 1H, J¼16.8, 5.8, 1.9 Hz),
1.31–1.12 (m, 1H), 0.81–0.57 (m, 4H); 13C 138.8, 128.7, 128.5, 126.8,
86.4, 71.0, 65.0, 27.6, 8.0, ꢂ0.4. Anal. Calcd for C13H13N3: C, 73.91; H,
6.20. Found: C, 73.11; H, 6.20.
4.4.5. 4-Cyclohex-1-en-1-yl-1-phenylbut-3-yn-1-yl azide (2e)
Light-yellow oil that partly crystallizes over days in a freezer, mp
37–39 ꢀC. IR (cmꢂ1, KBr) 3327 br w, 3030 m, 2930 s, 2859 s, 2670 w,
2487 w, 2100 s, 1250 s, 758 s, 700 s. UV–vis (3
, Mꢂ1 cmꢂ1; ether;
1.3ꢁ10ꢂ4 M) 227 (12 000). NMR (CDCl3): 1H 7.43–7.29 (m, 5H), 6.03
(t, 1H, J¼1.8 Hz), 4.66 (t, 1H, J¼6.9 Hz), 2.80 (ABX, 1H, J¼16.9,
7.9 Hz), 2.75 (ABX, 1H, J¼16.9, 6.0 Hz), 2.11–2.01 (m, 4H), 1.67–1.50
(m, 4H); 13C 138.8, 134.6, 128.8, 128.6, 126.9, 120.6, 85.1, 82.6, 65.0,
29.3, 28.2, 25.7, 22.4, 21.6. Anal. Calcd for C16H17N3: C, 76.46; H,
6.82. Found: C, 76.37; H, 6.92.
4.7. General procedure for the synthesis of pyrroles 3a,f–h
(conventional)
A Schlenk flask, equipped with a magnetic stirring bar and fitted
with a rubber septum, was charged with azide 2 (1.00 mmol) and
1,2-dichloroethane (2 mL). Zinc chloride (1.0 M in ether; for 2a
0.20 mL, 0.20 mmol and for 2f–h 0.40 mL, 0.40 mmol) was added
dropwise with a syringe. The solution was stirred at 75 ꢀC (oil bath)
for 16 h. After cooling, silica gel column chromatography (10ꢁ2 cm,
hexanes/ethyl acetate 100:0/20:1) gave 3a (0.210 g, 90%), 3f
(0.108 g, 51%), 3g (0.100 g, 61%), and 3h (0.130 g, 65%).
4.5. General procedure for the synthesis of but-3-yn-1-yl
azides 2f–h [DIAD, (PhO)2P(O)N3]6
Diisopropyl azodicarboxylate (1.2 mL, 3.1 mmol) was slowly
added to a solution of Ph3P (1.5 g, 5.7 mmol) in THF (25 mL) at 0 ꢀC
and the reaction mixture was stirred for 20 min. The solution of
but-3-yn-1-ol 1 (4 mmol) in THF (15 mL), cooled to 0 ꢀC, was added
slowly, followed by diphenylphosphoryl azide (1.4 mL, 6.5 mmol),
via syringe. Then stirring was continued for 3 h. The reaction
mixture was poured into water (ca. 20 mL) and extracted with ethyl
acetate (4ꢁ20 mL). The combined organic phases were washed
with saturated aq NaCl (2ꢁ50 mL) and dried over anhydrous
MgSO4. The solvent was removed by rotary evaporation. Silica gel
column chromatography (hexanes/chloroform 50:1/10:1) gave 2f
(0.738 g, 77%), 2g (0.498 g, 65%), and 2h (0.526 g, 62%).
4.7.1. 2-(4-Methylphenyl)-5-phenyl-1H-pyrrole (3a)
White solid. UV–vis (
3
, Mꢂ1 cmꢂ1; ether; 5.6ꢁ10ꢂ5 M) 230
(12 000), 326 (28 000). 13C NMR (CDCl3) 136.3, 133.4, 132.8, 132.7,
129.7, 129.0, 126.4, 123.9, 123.2, 107.9, 107.5, 21.3. 1H NMR, IR, and
MS data and mp matched with those reported earlier.23
4.7.2. 2-(4-Fluorophenyl)-5-(4-methylphenyl)-1H-pyrrole (3b)
White solid, mp 183–185 ꢀC. IR (cmꢂ1, KBr) 3460 br m, 1502 m,
1276 m, 1234 m, 1052 m, 833 s, 775 s. UV–vis (3
, Mꢂ1 cmꢂ1; ether;
3.2ꢁ10ꢂ5 M) 230 (15 000), 325 (42 000). NMR (CDCl3): 1H 8.45 (s,
1H), 7.48 (dd, 2H, J¼8.8, 5.227 Hz), 7.42 (d, 2H, J¼8.0 Hz), 7.21 (d, 2H,
J¼8.0 Hz), 7.09 (dd/apparent t, 2H, J¼8.8, 8.827 Hz), 6.55–6.48 (m,
2H), 2.37 (s, 3H); 13C 161.7 (d, J¼246.1 Hz), 136.4, 133.5, 132.0, 129.8,
4.5.1. cis-2-[(4-Methylphenyl)ethynyl]cyclohexyl azide (2f)
Light-yellow oil. IR (cmꢂ1, neat) 3320 br w, 2942 s, 2863 s, 2511
w, 2097 s, 1509 s, 1449 s, 1261 s, 1104 m, 817 s. UV–vis (3 ;
, Mꢂ1 cmꢂ1