PAPER
Synthesis of 2-(1H-1,2,3-Triazol-1-yl)-1,4-naphthoquinones
3223
13C NMR (100 MHz, CDCl3): d = 30.3, 68.6, 121.5, 126.6, 127.2,
131.1, 131.5, 134.4, 135.0, 139.4, 156.6, 179.4, 183.8.
Anal. Calcd for C21H12O4N4·1.0H2O: C, 62.69; H, 3.51; N, 13.92.
Found: C, 62.73; H, 3.42; N, 13.61.
LC-MS: m/z [M + Na]+ calcd for C15H13N3NaO3: 306.2718; found:
LC-MS: m/z [M + H]+ calcd for C21H13O4N4: 385.0937; found:
306.0782.
385.0888.
Anal. Calcd for C15H13N3O3·0.15H2O: C, 63.0; H, 4.69; N, 14.69.
Found: C, 63.85; H, 4.70; N, 14.03.
[1-(1,4-Dioxo-1,4-dihydronaphthalen-2-yl)-1H-1,2,3-triazol-4-
yl]methyl 4,6-Di-O-acetyl-2,3-dideoxy-b-D-erythro-hex-2-
enopyranoside (3i)
( )-2-[4-(1-Hydroxyethyl)-1H-1,2,3-triazol-1-yl]-1,4-naphtho-
quinone (3e)
Yellow solid; yield: 70%; mp 194–196 °C; Rf = 0.4 (CH2Cl2–
Green solid; yield: 51%; mp 108–110 °C; Rf = 0.7 (CH2Cl2–EtOAc,
9:1); [a]D27 +56 (c 0.4, CH3Cl).
EtOAc, 9:1).
1H NMR (300 MHz, DMSO-d6): d = 2.05 (s, 3 H, CH3CO), 2.06 (s,
3 H, CH3CO), 4.05 (ddd, J = 9.6, 6.3, 3.6 Hz, 1 H, H-5), 4.15 (m, 2
H, H-6, H-6¢), 4.74 (d, J = 12 Hz, 1 H, OCH2), 4.86 (d, J = 12 Hz,
1 H, OCH2), 5.21 (dd, J = 9.6, 1.2 Hz, 1 H, H-4), 5.27 (d, J = 2.1
Hz, 1 H, H-1), 5.90 (m, 2 H, H-2, H-3), 7.50 (s, 1 H, = CH-naphth),
7.96 (m, 2 H, 2 Hnaphth), 8.07 (m, 1 H, Hnaphth), 8.15 (m, 1 H, Hnaphth),
8.67 (s, 1 H, Htriaz).
13C NMR (75 MHz, DMSO-d6): d = 20.6, 20.8, 60.2, 62.5, 64.7,
66.6, 93.0, 125.9, 126.4, 126.8, 128.0, 129.0, 131.2, 131.3, 134.6,
134.8, 140.3, 144.6, 169.9, 170.2, 178.7, 184.1.
1H NMR (400 MHz, CDCl3): d = 1.67 (d, J = 6.4, 3 H, CH3), 2.09
(br s, 2 H, OH, R or S), 5.20 (br d, J = 6.0 Hz, CH), 7.73 (s, 1
H, = CH-naphth), 7.84 (m, 2 H, Hnaphth), 8.20 (m, 2 H, Hnaphth), 8.58
(s, 1 H, Htriaz).
13C NMR (100 MHz, CDCl3): d = 23.3, 63.3, 122.9, 126.9, 127.6,
131.4, 131.8, 134.7, 135.3, 139.6, 153.6, 179.6, 184.1.
LC-MS: m/z [M + H]+ calcd for C14H12N3O3: 270.0879; found:
270.0830.
Anal. Calcd for C23H21N3O8: C, 59.10; H, 4.53; N, 8.99. Found: C,
59.12; H, 4.80; N, 8.63.
( )-2-[4-(2-Hydroxypropyl)-1H-1,2,3-triazol-1-yl]-1,4-naphtho-
quinone (3f)
Yellow solid; yield: 66%; mp 188–190 °C; Rf = 0.3 (CH2Cl2–
EtOAc, 9:1).
2-(4-Propyl-1H-1,2,3-triazol-1-yl)-1,4-naphthoquinone (3j)
The typical procedure was used except that Et3N (10 mol% on 2j)
was added to the mixture and the reaction was continued for 2 h at
15–20 °C in the absence of light to give a yellow solid; yield: 80%;
mp 119–121 °C; Rf = 0.6 (CH2Cl2–EtOAc, 9:1).
1H NMR (400 MHz, DMSO-d6): d = 0.95 (t, 3 H, J = 7.6 Hz), 1.69
(m, 2 H), 2.72 (t, 2 H, J = 7.2 Hz), 7.44 (s, 1 H, = CH-naphth), 7.95
(m, 2 H, Hnaphth), 8.05 (m, 1 H, Hnaphth), 8.13 (m, 1 H, Hnaphth), 8.42
(s, 1 H, Htriaz).
1H NMR (400 MHz, CDCl3): d = 1.31 (d, J = 9.6, 3 H, CH3), 1.26
(br s, 1 H, OH, R or S), 2.59 (br s, 1 H, OH, R or S), 2.91 (dd, J = 8,
14.8 Hz), 3.02 (dd, 1 H, J = 8, 14.8 Hz), 4.23 (br d, J = 4.4 Hz, CH),
7.72 (s, 1 H, = CH-naphth), 7.83 (m, 2 H, Hnaphth), 8.14 (d, J = 6.8
Hz, 1 H, Hnaphth), 8.18 (d, J = 6.8 Hz, 1 H, Hnaphth), 8.51 (s, 1 H,
Htriaz).
13C NMR (100 MHz, CDCl3): d = 23.0, 34.9, 67.0, 124.2, 126.4,
126.5, 127.2, 131.1, 131.5, 134.3, 134.9, 139.4, 146.2, 179.4, 183.8.
13C NMR (100 MHz, DMSO-d6): d = 13.6, 22.2, 26.9, 124.2, 126.0,
126.9, 131.3, 131.4, 134.7, 134.9, 140.3, 148.0, 179.0, 184.3.
Anal. Calcd for C15H13N3O3·0.1H2O: C, 63.10; H, 4.67; N, 14.74.
Found: C, 63.18; H, 4.62; N, 14.83.
Anal. Calcd for C15H13N3O2: C, 67.40; H, 4.90; N, 15.72. Found: C,
67.53; H, 4.70; N, 15.36.
Ethyl 1-(1,4-Dioxo-1,4-dihydronaphthalen-2-yl)-1H-1,2,3-tri-
azole-4-carboxylate (3g)
Yellow solid; yield: 77%; mp 144–150 °C; Rf = 0.6 (CH2Cl2–
EtOAc, 9:1).
Acknowledgment
The authors are grateful to FACEPE for financial support and for
providing a fellowship to one of us (W.S.N.). Our thanks are also
due to Analytical Centers CENAPESQ-UFRPE and DQF-UFPE,
CAPES and CNPq. We also thank Professor Patrícia L. B. Araujo
(DQ-UFRPE) for her kind suggestions.
1H NMR (400 MHz, DMSO-d6): 1.34 (t, J = 7.1 Hz, 3 H), 4.39 (q,
J = 7.2 Hz, 2 H), 7.61 (s, 1 H, = CH-naphth), 7.98 (d, J = 5.7, 5.7
Hz, 2 H, Hnaphth), 8.09 (dd, J = 5.9, 3.3 Hz, 1 H, Hnaphth), 8.16 (dd,
J = 5.9, 3.3 Hz, 1 H, Hnaphth), 9.09 (s, 1 H, Htriaz).
13C NMR (100 MHz, DMSO-d6): d = 14.2, 61.1, 104.3, 126.0,
126.8, 131.0, 131.3, 134.8, 139.4, 139.9, 159.7, 178.3, 183.9.
LC-MS: m/z [M + Na]+ calcd for C15H11N3NaO4: 320.0647; found:
References
320.0598.
(1) Nascimento, W. S.; da Silva, M. G.; de Oliveira, R. N.;
Camara, C. A. Orbital: Electron. J. Chem. 2010, 2, 5.
(2) Silverman, R. B. The Organic Chemistry of Drug Design
and Drug Action; Elsevier Academic Press: Burlington
(MA), 2004.
Anal. Calcd for C15H11N3O4: C, 60.61; H, 3.73; N, 14.14. Found: C,
61.10; H, 3.52; N, 14.46.
2-{[1-(1,4-Dioxo-1,4-dihydronaphthalen-2-yl)-1H-1,2,3-triazol-
4-yl]methyl}-1H-isoindole-1,3(2H)-dione (3h)
Green solid; yield: 84%; mp 214–216 °C; Rf = 0.6 (hexane–EtOAc,
6:4).
1H NMR (400 MHz, DMSO-d6): d = 4.99 (s, 2 H, CH2-phth), 7.47
(s, 1 H, = CH-naphth), 7.87 (dd, J = 5.2,3.2 Hz, 2 H, phth), 7.94 (m,
2 Hphth and 2 Hnaphth), 8.06 (dd, J = 5.8, 3.0 Hz, 1 H, Hnaphth), 8.13
(dd, J = 5.8, 3.0 Hz, 1 H, Hnaphth), 8.67 (s, 1 H, Htriaz).
(3) Li, J. J.; Johnson, D. S. Modern Drug Synthesis; John Wiley:
Hoboken (NJ), 2010.
(4) Meldal, M.; Tornøe, C. W. Chem. Rev. 2008, 108, 2952.
(5) Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem.
2002, 67, 3057.
(6) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless,
K. B. Angew. Chem. Int. Ed. 2002, 41, 2596.
(7) (a) Rodionov, V. O.; Fokin, V. V.; Finn, M. G. Angew.
Chem. Int. Ed. 2005, 44, 2210. (b) Himo, F.; Lovell, T.;
Hilgraf, R.; Rostvtsev, V. V.; Noodleman, L.; Sharpless,
K. B.; Folkin, V. V. J. Am. Chem. Soc. 2005, 127, 210.
13C NMR (100 MHz, DMSO-d6): d = 32.6, 123.2, 125.5, 125.7,
126.0, 126.6, 131.1, 131.2, 131.5, 134.5, 134.6, 134.7, 140.1, 143.2,
167.3, 178.5, 183.9.
Synthesis 2011, No. 20, 3220–3224 © Thieme Stuttgart · New York