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Synthesis of aryl azides and vinyl azides
via proline promoted CuI-catalyzed coupling
reaction
Wei Zhua and Dawei Mab*
a
Department of Chemistry, Fudan University, Shanghai 200433, bState Key Laboratory of Bioorganic
and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 354 Fenglin Lu, Shanghai 200032, China.
Supporting information
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Experimental
General Procedure for Table 1: A mixture of 2 mmol of aryl iodide, 2.4
mmol of sodium azide, 0.2 mmol of copper iodide, 0.4 mmol of L-proline and 0.4
mmol of NaOH in 4 mL DMSO in a sealed tube was heated to suitable temperature
under argon.
After the reaction was completed monitored by TLC, the cooled
mixture was partitioned between ethyl acetate and water (If a substrate has a
carboxylate group the reaction mixtre should be acidified to pH =
1 before
extraction). The organic layer was separated, and the aqueous layer was extracted
with ethyl acetate twice. The combined organic layers were washed with brine, dried
over Mg2SO4, and concentrated in vacuo. The residual oil was loaded on a silica gel
column and eluted with petroleum ether/ethyl acetate to afford the product.
General Procedure for Table 2: A mixture of 2 mmol of aryl bromide, 4 mmol
of sodium azide, 0.2 mmol of copper iodide, 0.6 mmol of L-proline and 0.6 mmol of
NaOH in 4 mL EtOH/H2O (7:3) in a sealed tube was heated to 95 ºC under argon.
After the reaction was completed monitored by TLC, the cooled mixture was
partitioned between ethyl acetate and water (If a substrate has a carboxylate group the
reaction mixtre should be acidified to pH =
1 before extraction). The organic layer
was separated, and the aqueous layer was extracted with ethyl acetate twice. The
combined organic layers were washed with brine, dried over Mg2SO4, and
concentrated in vacuo. The residual oil was loaded on a silica gel column and eluted
with petroleum ether/ethyl acetate to afford the product.
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General Procedure for Table 3: A mixture of 2 mmol of vinyl iodide, 2.4
mmol of sodium azide, 0.2 mmol of copper iodide, 0.4 mmol of L-proline sodium salt
in 4 ml DMSO in a sealed tube was heated to 50-70 oC under argon.
After the
reaction was completed monitored by TLC, the cooled mixture was partitioned
between ethyl acetate and water. The organic layer was separated, and the aqueous
layer was extracted with ethyl acetate twice. The combined organic layers were
washed with brine, dried over Mg2SO4, and concentrated in vacuo. The residual oil
was loaded on a silica gel column and eluted with petroleum ether/ethyl acetate to
afford the product.
4-Methoxyphenylazide1. 1H NMR (CDCl3, 300 MHz) δ 3.80 (s, 3H),
6.87-6.98 (m, 4H); MS m/z 149 (M+); IR (film cm-1) 2106.
Phenylazide2. 1H NMR (CDCl3, 300 MHz) δ 7.03 (m, 2H), 7.15 (t, J = 7.5
Hz, 1H), 7.36 (m, 2H); MS m/z 119 (M+); IR (film cm-1) 2101.
4-Methylphenylazide3. 1H NMR (CDCl3, 300 MHz) δ 2.35 (s, 3H), 6.93 (d,
J = 6.6 Hz, 2H), 7.16 (d, J = 6.6 Hz, 2H); MS m/z 133 (M+); IR (film cm-1) 2106.
3,5-Dimethylphenylazide. 1H NMR (CDCl3, 300 MHz) δ 2.23 (s, 6H), 6.63 (s,
2H), 6.76 (s, 1H); MS m/z 147 (M+), 119, 105, 91, 77, 63, 51; HRMS found m/z
147.0793 (M+); C8H9N3 requires 147.0796; IR (film cm-1) 2957, 2922, 2106, 1612,
1593, 1471, 1378, 1316, 1239, 837, 681.
4-Bromophenylazide4. 1H NMR (CDCl3, 300 MHz) δ 6.91 (m, 2H), 7.46 (m,
2H); MS m/z 197 (M+); IR (film cm-1) 2131, 2109.
4-Hdroxyphenylazide5. 1H NMR (CDCl3, 300 MHz) δ 5.68 (brs, 1H),
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6.83~6.94 (m, 4H); MS m/z 135 (M+); IR (film cm-1) 2114.
4-Aminophenylazide6. 1H NMR (CDCl3, 300 MHz) δ 3.65 (brs, 2H), 6.67 (m,
2H), 6.85 (m, 2H); MS m/z 134 (M+); IR (film cm-1) 2109.
3-Fluorophenylazide7. 1H NMR (CDCl3, 300 MHz) δ 6.73 (m, 1H), 6.85 (m,
2H), 7.32 (m, 1H); MS m/z 137 (M+); IR (film cm-1) 2123.
2-Methoxyphenylazide8. 1H NMR (CDCl3, 300 MHz) δ 3.87 (s, 3H),
6.87~7.13 (m, 4H); MS m/z 149 (M+); IR (film cm-1) 2114.
2-Fluorophenylazide9. 1H NMR (CDCl3, 300 MHz) δ 7.07~7.15 (m, 4H);
MS m/z 137 (M+); IR (film cm-1) 2123.
2-Azidobenzoic acid10. 1H NMR (CDCl3, 300 MHz) δ 7.27 (m, 2H), 7.63 (m,
1H), 8.13 (m, 1H); MS m/z 163 (M+); IR (film cm-1) 2131.
4-Hydroxymethylphenylazide11. 1H NMR (CDCl3, 300 MHz) δ 1.80 (brs,
1H), 4.67 (s, 2H), 7.02 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H); MS m/z 149 (M+);
IR (film cm-1) 2111.
4-Azido-N-Boc-phenylalanine 2. 1H NMR (CDCl3, 300 MHz) δ 1.31~1.46
(m, 9H), 2.92~3.21 (m, 2H), 4.37 (m, 0.4H), 4.59 (m, 0.6H), 5.02 (d, J = 7.5 Hz,
0.6H), 6.66 (m, 0.4H), 6.96 (m, 2H), 7.22 (m, 2H), 8.72 (brs, 1H); ESI MS m/z 329
(M + Na)+; ESI HRMS found m/z 329.1222 (M + Na)+; C14H18N4O4Na requires
329.1226; IR (film cm-1) 2982, 2116, 1718, 1609, 1509, 1370, 1289, 1249, 1167, 1050;
[α]D19 = 12.7 (c = 1.05, CHCl3).
2-Methylphenylazide12. 1H NMR (CDCl3, 300 MHz) δ 2.21 (s, 3H),
7.04~7.25 (m, 4H); MS m/z 133 (M+); IR (film cm-1) 2114.
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4-Chlorophenylazide13. 1H NMR (CDCl3, 300 MHz) δ 7.23 (m, 2H), 7.43
(m, 2H); MS m/z 153 (M+); IR (film cm-1) 2133, 2096.
3-Azidobenzoic acid14. 1H NMR (CDCl3, 300 MHz) δ 7.27 (m, 1H), 7.48 (t,
J = 8.4, 1H), 7.78 (t, J = 1.8 Hz, 1H), 7.90 (dd, J = 1.8, 8.4 Hz, 1H); MS m/z 163 (M+);
IR (film cm-1) 2132.
3-Aminophenylazide15. 1H NMR (CDCl3, 300 MHz) δ 3.75 (brs, 2H), 6.31
(m, 1H), 6.43 (m, 2H), 7.14 (m, 1H); MS m/z 134 (M+); IR (film cm-1) 2115.
3-Methoxyphenylazide16. 1H NMR (CDCl3, 300 MHz) δ 3.80 (s, 3H), 6.55
(d, J = 2.1 Hz, 1H), 6.67 (m, 2H), 7.25 (m, 1H); MS m/z 137 (M+); IR (film cm-1)
2111.
3,5-Dimethoxyphenylazide. 1H NMR (CDCl3, 300 MHz) δ 3.80 (s, 3H),
3.87 (s, 3H), 6.39 (dd, J = 8.7, 2.7 Hz, 1H), 6.48 (d, J = 2.7 Hz, 1H), 7.41 (d, J = 8.7
Hz, 1H); MS m/z 179 (M+), 158, 107, 79, 63, 51; HRMS found m/z 179.0698 (M+);
C8H9N3O2 requires 179.0695; IR (film cm-1) 3005, 2962, 2137, 2107, 1592, 1490,
1465, 1438, 1411, 1308, 1211, 1062.
(E)-Stryrylazide 417. 1H NMR (CDCl3, 300 MHz) δ 5.69 (d, J = 9 Hz, 1H),
6.35 (d, J = 9 Hz, 1H), 7.20~7.36 (m, 3H), 7.60 (m, 2H); MS m/z 145 (M+); IR (film
cm-1) 2112, 1635.
(E)-4-Methoxystyrylazide 5. 1H NMR (CDCl3, 300 MHz) δ 3.81 (s, 3H),
5.63 (d, J = 8.7 Hz, 1H), 6.25 (d, J = 8.7 Hz, 1H), 6.86 (d, J = 6.6 Hz, 2H), 7.54 (d, J
= 6.9 Hz, 2H); MS m/z 175 (M+), 147, 132, 120, 104, 91, 77, 63, 51; HRMS found
m/z 175.0747 (M+); C9H9N3O requires 175.0746; IR (film cm-1) 2933, 2110, 1634,
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1606, 1512, 1399, 1304, 1254, 1177, 1035, 837.
(E)-4-Chlorostyrylazide 618. 1H NMR (CDCl3, 300 MHz) δ 5.63 (d, J = 8.7
Hz, 1H), 6.37 (d, J = 8.1 Hz, 1H), 7.28 (m, 2H), 7.52 (m, 2H); MS m/z 179 (M+); IR
(film cm-1) 2111, 1633.
Azidomethylenecyclohexane 2419. 1H NMR (CDCl3, 300 MHz) δ 1.47 (m,
6H), 2.03~2.15 (m, 4H) 5.90 (s, 1H); MS m/z 137 (M+); IR (film cm-1) 2104, 1666.
(E)-1-Azidotridec-1-ene 23. 1H NMR (CDCl3, 300 MHz) δ 0.88 (t, J = 6.9
Hz, 3H), 1.23 (m, 18H), 2.04 (q, J = 6.9 Hz, 2H), 4.86 (q, J = 7.5 Hz, 1H), 6.10 (d, J =
7.5 Hz, 1H); MS m/z 223 (M+), 195, 180, 166, 152, 138, 124, 110, 96, 82, 69, 57, 43;
HRMS found m/z 223.2044 (M+); C13H25N3 requires 223.2048; IR (film cm-1) 3037,
2957, 2926, 2856, 2106, 1645, 1467, 1388, 1282, 725.
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