The Journal of Organic Chemistry
Article
7.49−7.43 (m, 2H), 7.38−7.33 (m, 2H), 7.08−7.01 (m, 2H, Ar), 3.90
(s, 3H, OCH3); 13C{1H} NMR (CDCl3, 100.6 MHz, δ) 161.1 (q),
138.5 (q), 135.3 (q), 133.2 (t), 129.6 (q), 129.0 (t), 127.4 (t), 120.8
(q), 114.7 (t), 94.1 (q), 85.9 (q), 79.5 (q), 55.8 (p); IR (cm−1) ν
2231 (CC); HRMS ESI [M + H]+ calcd for C17H12ClIN3O+
435.9708, found 435.9700.
4-(5-Iodo-1-(3,4,5-trimethoxybenzyl)-1H-1,2,3-triazol-4-yl)but-3-
yn-1-ol (9p). This compound was prepared in accordance with the
general procedure from 1,2,3-trimethoxybenzyl azide 8c (52.7 mg,
0.236 mmol), 1-iodo(buta-1,3-diyne) 7g (52 mg, 0.236 mmol),
[CuI(PPh3)3] (4.62 mg, 2 mol %), and 2,6-lutidine (1.01 mg) with a
reaction time of 18 h. The crude product was purified by column
chromatography (eluent: hexane/EtOAc = 3:1 → 2:1) to afford a
white solid (68 mg, 65% yield): mp 161−162.5 °C; 1H NMR
(CDCl3, 400.13 MHz, δ) 6.51 (s, 2H), 5.46 (s, 2H, CH2), 3.84 (t, J =
6.2 Hz, 2H, CH2), 3.81 (s, 9H, 3OCH3), 2.74 (t, J = 6.2 Hz, 2H,
CH2); 13C{1H} NMR (CDCl3, 100.6 MHz, δ) 153.7 (q), 138.7 (q),
138.4 (q), 129.4 (q), 105.4 (t), 93.4 (q), 83.7 (q), 71.6 (q), 61.0 (p),
60.9 (s), 56.4 (p), 55.0 (s), 24.0 (s); IR (cm−1) ν 3485 (OH), 2244
(CC); HRMS ESI [M + Na]+ calcd for C16H18IN3O4Na+ 466.0234,
found 466.0233.
8H), 6.94−6.88 (m, 2H), 5.62 (s, 2H, CH2), 3.85 (s, 3H, OCH3);
13C{1H} NMR (CDCl3, 100.6 MHz, δ) 161.0 (q), 134.5 (q), 133.8
(q), 133.5 (t), 131.9 (t), 129.1 (t), 129.0 (t), 128.8 (t), 128.5 (t),
128.3 (t), 124.2 (q), 122.5 (q), 114.5 (t), 113.2 (q), 103.8 (q), 95.3
(q), 78.5 (q), 72.6 (q), 55.55 (p), 53.4 (s); IR (cm−1) ν 2217 (C
C); HRMS ESI [M + H]+ calcd for C26H20N3O+ 390.1601, found
390.1605.
4-(1-Benzyl-4-(phenylethynyl)-1H-1,2,3-triazol-5-yl)-2-methyl-
but-3-yn-2-ol (13b). This compound was prepared in accordance
with the general procedure from 5-iodo-1H-1,2,3-triazole 9b (19.6
mg, 0.059 mmol) and 2-methylbut-3-yn-2-ol 12b (8.6 mg, 0.102
mmol, 2 equiv) with a reaction time of 1 h. The crude product was
purified by column chromatography (eluent: benzene/acetone = 10:1
→ 5:1) to afford a white solid (15.7 mg, 90% yield): 1H NMR
(CDCl3, 400.13 MHz, δ) 7.64−7.48 (m, 2H), 7.41−7.27 (m, 8H),
5.54 (s, 2H, CH2), 1.60 (s, 6H, 2CH3); 13C{1H} NMR (CDCl3, 100.6
MHz, δ) 134.4 (q), 134.3 (q), 131.9 (t), 129.1 (t), 129.1 (t), 128.8
(t), 128.6 (t), 128.2 (t), 123.3 (q), 122.3(q), 108.5 (q), 95.4 (q), 78.1
(q), 67.1 (q), 65.8 (q), 53.5 (s), 31.1 (p); IR (cm−1) ν 3367 (OH),
2229 (CC); HRMS ESI [M + Na]+ calcd for C22H19N3ONa+
364.1420, found 364.1418.
1-Benzyl-4,5-bis((4-methoxyphenyl)ethynyl)-1H-1,2,3-triazole
(13c). This compound was prepared in accordance with the general
procedure from 5-iodo-1H-1,2,3-triazole 9c (21.8 mg, 0.05 mmol)
and 1-ethynyl-4-methoxybenzene 12a (13.2 mg, 0.100 mmol, 2 equiv)
with a reaction time of 13 h. The crude product was purified by
column chromatography (eluent: C6H6/Acetone = 100:1) to afford a
yellowish oil (16 mg, 79% yield): 1H NMR (CDCl3, 400.13 MHz, δ)
7.53−7.47 (m, 2H), 7.46−7.41 (m, 2H), 7.39−7.30 (m, 5H), 6.94−
6.89 (m, 2H), 6.89−6.84 (m, 2H), 5.61 (s, 2H, CH2), 3.85 (s, 3H,
OCH3), 3.82 (s, 3H, OCH3); 13C{1H} NMR (CDCl3, 100.6 MHz, δ)
161.0 (q), 160.2 (q), 134.6 (q), 134.1 (q), 133.51 (t), 133.46 (t),
129.0 (t), 128.7 (t), 128.3 (t), 123.8 (q), 114.6 (q), 114.4 (t), 114.2
(t), 113.3 (q), 103.6 (q), 95.5 (q), 77.2 (q), 72.7 (q), 55.5 (p), 55.4
(p), 53.3 (s); IR (cm−1) ν 2215 (CC); HRMS ESI [M + Na]+
calcd for C27H21N3O2Na+ 442.1526, found 442.1519.
2-((1-Benzyl-4-(p-tolylethynyl)-1H-1,2,3-triazol-5-yl)ethynyl)-
N,N-dimethylaniline (13d). This compound was prepared in
accordance with the general procedure from 5-iodo-1H-1,2,3-triazole
9a (100 mg, 0.250 mmol) and 2-ethynyl-N,N-dimethylaniline 12c
(40.0 mg, 0.276 mmol, 1.1 equiv) with a reaction time of 5 h. The
crude product was purified by column chromatography (eluent:
C6H6) to afford a white solid (73 mg, 70% yield): 1H NMR (CDCl3,
400.13 MHz, δ) 7.46−7.42 (m, 2H), 7.41−7.29 (m, 7H), 7.17−7.13
(m, 2H), 6.97−6.85 (m, 2H), 5.63 (s, 2H, CH2), 2.94 (s, 6H,
N(CH3)2), 2.37 (s, 3H, CH3); 13C{1H} NMR (CDCl3, 100.6 MHz,
δ) 155.4 (q), 139.3 (q), 134.6 (q), 134.60 (t), 134.0 (q), 131.7 (t),
131.0 (t), 129.3 (t), 129.1 (t), 128.7 (t), 128.2 (t), 124.3 (q), 120.3
(t), 119.4 (q), 117.2 (t), 112.5 (q), 103.4 (q), 95.5 (q), 78.6(q), 78.1
(q), 53.2 (s), 43.7 (p), 21.7 (p); IR (cm−1) ν 2216 (CC); HRMS
ESI [M + H]+ calcd for C28H25N4+ 417.2074, found 417.2073. Single
crystals of 13d were grown from the solution in chloroform by the
vapor exchange with hexane. Crystallographic data (excluding
structure factors) for the structures reported in this work have been
deposited with the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC 1869739 (Figure S1).
4-(4-(3-Methoxyprop-1-yn-1-yl)-1-(3,4,5-trimethoxybenzyl)-1H-
1,2,3-triazol-5-yl)but-3-yn-1-ol (13e). This compound was prepared
in accordance with the general procedure from 5-iodo-1H-1,2,3-
triazole 9j (66.0 mg, 0.149 mmol) and but-3-yn-1-ol 12d (15.7 mg,
0.223 mmol, 1.5 equiv) with a reaction time of 7 h.The crude product
was purified by column chromatography (eluent: hexane/EtOAc =
2:1 → 1:1) to afford a beige solid (44 mg, 77% yield): mp 73−75 °C;
1H NMR (CDCl3, 400.13 MHz, δ) 6.55 (s, 2H), 5.43 (s, 2H, CH2),
4-(1-Hexyl-5-iodo-1H-1,2,3-triazol-4-yl)-2-methylbut-3-yn-2-ol
(9q). This compound was prepared in accordance with the general
procedure from 1-azidohexane 8i (81.5 mg, 0.641 mmol), 1-
iodo(buta-1,3-diyne) 7j (150 mg, 0.641 mmol), [CuI(PPh3)3] (31.3
mg, 5 mol %), and 2,6-lutidine (2.75 mg) with a reaction time of 18 h.
The crude product was purified by column chromatography (eluent:
hexane/EtOAc = 5:1 → 3:1) to afford a beige solid (112 mg, 48%
1
yield): H NMR (CDCl3, 400.13 MHz, δ) 4.36 (t, J = 7.3 Hz, 2H,
CH2), 2.08 (s, 1H, OH), 1.90−1.88 (m, 2H, CH2), 1.65 (s, 6H,
2CH3), 1.33−1.31 (m, 6H, 3CH2), 0.98−0.81 (m, 3H, CH3);
13C{1H} NMR (CDCl3, 100.6 MHz, δ) 137.5 (q), 99.7 (q), 84.1 (q),
71.8 (q), 65.7 (q), 51.4 (s), 31.4 (p), 31.2 (s), 29.9 (s), 26.1 (s), 22.5
(s), 14.1 (p); IR (cm−1) ν 3367 (OH), 2225 (CC); HRMS ESI [M
+ Na]+ calcd for C13H20IN3ONa+ 384.0543, found 384.0543.
Ethyl 2-(4-(3-Hydroxy-3-methylbut-1-yn-1-yl)-5-iodo-1H-1,2,3-
triazol-1-yl)acetate (9r). This compound was prepared in accordance
with the general procedure from azide 8d (82.7 mg, 0.641 mmol), 1-
iodo(buta-1,3-diyne) 7j (150 mg, 0.641 mmol), [CuI(PPh3)3] (12.5
mg, 2 mol %), and 2,6-lutidine (2.75 mg) with a reaction time of 5 h.
The crude product was purified by column chromatography (eluent:
hexane/EtOAc = 3:1 → 2:1) to afford a light yellow oil (215 mg, 92%
yield): 1H NMR (CDCl3, 400.13 MHz, δ) 5.16 (s, 2H, CH2), 4.28 (q,
J = 7.1 Hz, 2H, OCH2CH3), 2.12 (s, 1H, OH), 1.65 (s, 6H, 2CH3),
1.30 (t, J = 7.1 Hz, 3H, OCH2CH3); 13C{1H} NMR (CDCl3, 100.6
MHz, δ) 165.2 (q), 138.2 (q), 100.1 (q), 85.7 (q), 71.5 (q), 65.7 (q),
62.7 (s), 51.8 (s), 31.3 (p), 14.2 (p); IR (cm−1) ν 3381 (OH), 2244
(CC), 1750 (CO); HRMS ESI [M + Na]+ calcd for
C11H14IN3O3Na+ 385.9972, found 385.9969.
General Procedure for the Sonogashira Coupling. 5-Iodo-1H-
1,2,3-triazoles 9a−c,i,j,p (1 equiv), CuI (10 mol %), K3PO4 (1.1
equiv), and Pd(PPh3)4 (5 mol %) were placed in a vial. The vial was
sealed, and the mixture was evacuated and flushed with Ar several
times. THF (1 mL) was added; the mixture was stirred at room
temperature for 10 min, and then an alkyne 12a−f (1.1−2 equiv) was
added. The vial with the reaction mixture was placed in a preheated
oil bath (65 °C) and stirred at this temperature for 1−16 h (TLC
control). After cooling to room temperature, the reaction mixture was
filtered through a pad silica gel and the pad was washed with CH2Cl2
(3 × 10 mL). The solvent was removed under reduced pressure, and
the crude product was purified by column chromatography on silica
gel.
1-Benzyl-5-((4-methoxyphenyl)ethynyl)-4-(phenylethynyl)-1H-
1,2,3-triazole (13a). This compound was prepared in accordance
with the general procedure from 5-iodo-1H-1,2,3-triazole 9b (19.3
mg, 0.050 mmol) and 1-ethynyl-4-methoxybenzene 12a (13.2 mg,
0.100 mmol, 2 equiv) with a reaction time of 16 h. The crude product
was purified by chromatography (eluent: hexane/EtOAc = 5:1) to
4.35 (s, 2H, CH2), 3.91−3.69 (m, 11H, 3OCH3, CH2), 3.44 (s, 3H,
OCH3), 2.77 (t, J = 6.2 Hz, 2H, CH2); 13C{1H} NMR (CDCl3, 100.6
MHz, δ) 153.7 (q), 138.4 (q), 133.2 (q), 129.9 (q), 124.2 (q), 105.5
(t), 102.7 (q), 91.4 (q), 75.5 (q), 66.8 (q), 60.9 (p), 60.5 (s), 60.4
(s), 57.9 (p), 56.4 (p), 53.4 (s), 24.3 (s); IR (cm−1) ν 3411 (OH),
1
afford a beige solid (15 mg, 77% yield): H NMR (CDCl3, 400.13
MHz, δ) 7.58−7.56 (m, 2H), 7.48−7.42 (m, 2H), 7.38−7.33 (m,
1934
J. Org. Chem. 2019, 84, 1925−1940