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DOI: 10.1055/s-0029-1218267
One-Pot Synthesis of 1,4-Disubstituted 1,2,3-Triazoles from Aldehydes and Amines
Publication History
Publication Date:
08 October 2009 (online)
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Abstract
A one-pot, three-step synthesis of 1,4-disubstituted 1,2,3-triazoles from aldehyde and amine has been developed by in situ transformation of aldehyde into alkyne, followed by diazo-transfer of amine into azide and subsequent cycloaddition. This procedure allowed the synthesis of fluorescent amino acid derivatives as well as glycoconjugate mimetics.
Key words
aldehydes - amines - cycloadditions - one-pot reaction - triazoles
- Supporting Information for this article is available online:
- Supporting Information
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References and Notes
General Procedure
To
a solution of aldehyde (1 equiv) in a mixture MeOH-CH2Cl2 (4
mL/4 mL for 0.5 mmol of aldehyde) were added K2CO3 (4
equiv) and the Bestmann-Ohira reagent (1.8 equiv). The
mixture was stirred at r.t. until complete conversion of aldehyde
to alkyne (TLC monitoring -
6 h maximum). Amine
hydrochloride salt (1.2 equiv), CuSO5˙5H2O
(1.2 equiv) and the imidazole-1-sulfonyl azide (1.2 equiv) were
then added to the reaction mixture and stirred at r.t. to transform
the amine into the azide intermediate. Reaction was judged to be
complete when imidazole-1-sulfonyl azide spot disappeared on TLC
(4 h maximum). Finally, ascorbic acid (4 equiv) was added, and the
reaction was stirred at r.t. overnight. The mixture was filtered
through a pad of Celite, washed with MeOH, and the solvents evaporated
under vacuum. The residue was purified by column chromatography
on silica gel (40-63 µM) to afford the triazoyl
compound.
Analytical Data for Selected
Compounds
Compound 12: mp
191 ˚C; R
f
= 0.55
(EtOAc-cyclohexane = 1:1); [α]D -89.2
(c 0.48, CH2Cl2). ¹H
NMR (400 MHz, CDCl3): δ = 3.89 (s,
3 H), 5.37 (s, 2 H, CH2), 8.01-8.29 (m, 9 H),
8.67 (d, 1 H, J = 9.2
Hz). ¹³C NMR (100 MHz, CDCl3): δ = 51.0
(CH2), 53.3 (CH3), 124.3, 124.7, 125.0, 125.3, 126.2,
127.3, 127.5, 128.0, 128.4, 128.7 (CH), 131.0, 131.4, 131.5, 148.0,
166.9 (C). ESI-HRMS: m/z calcd
for C21H15N3NaO2: 364.1062;
found: 364.1057.
Compound 29:
mp 114 ˚C; R
f
= 0.48
(EtOAc); [α]D -35.2
(c 0.47, CH2Cl2). ¹H
NMR (400 MHz, CDCl3): δ = 1.31 (s,
3 H), 1.36 (s, 3 H), 1.45 (s, 3 H), 1.60 (s, 3 H), 1.83 (s, 3 H), 1.83-2.01
(m, 2 H), 3.52-3.53 (m, 1 H), 3.61-3.63 (m, 1
H), 3.67 (dd, 1 H, J = 6.4,
10.1 Hz), 3.90 (dd, 1 H, J = 7.4,
10.1 Hz), 3.95-3.97 (m, 1 H), 4.11-4.13 (m, 1
H), 4.25 (t, 1 H, J = 6.8
Hz), 4.37 (dd, 1 H, J = 2.8,
5.0 Hz), 4.39-4.51 (m, 6 H), 4.55-4.59 (m, 3 H),
4.70 (dd, 1 H, J = 2.3,
7.8 Hz), 5.19 (d, 1 H, J = 1.8
Hz), 5.60 (d, 1 H, J = 5.0
Hz), 6.60 (d, 1 H, J = 9.6
Hz), 7.20-7.33 (m, 15 H), 7.65 (s, 1 H). ¹³C
NMR (100 MHz, CDCl3): δ = 23.4, 24.3,
25.1, 26.1, 26.3 (CH3), 32.4, 46.9 (CH2),
47.8, 64.7, 65.3 (CH); 67.6 (CH2), 70.8, 70.9 (CH); 72.0,
72.3 (CH2), 72.7, 73.2 (CH), 73.4 (CH2), 74.2,
75.1, 77.3 (CH), 96.7 (CH), 109.0, 109.3 (C), 123.6, 127.8, 127.9,
128.6, 128.7 (CH), 137.3, 137.5, 138.2, 145.1, 170.0 (C). ESI-HRMS: m/z calcd for C44H54N4NaO10: 821.3738;
found: 821.3732.