SPECIAL TOPIC
N-Heterocyclic Carbenes of Indazole
2803
13C NMR (CDCl3): d = 191.6 (C=O), 145.2 (C-8a), 143.2 (C-3),
136.8 (C-1arom), 131.4 (C-3arom), 131.1 (C-7), 130.9 (C-2arom), 127.2
(C-5), 127.0 (C-4arom), 124.8 (C-4), 123.6 (C-4a), 123.1 (C-6), 119.6
(C-8), 42.5 [N(1)-CH3], 40.2 [N(2)-CH3].
was formed, whereas 1,2-dimethylindazolium bromide (3) was iso-
lated after dehydrohalogenations (Table 1).
3-Bromo-1,2-dimethylindazolium Bromide (19)
Yellowish solid, yield: 90 – 95%; mp 198 °C (dec.)
EIMS: m/z (%) = 342 (M+, 6), 327 (100).
IR (KBr): 3095, 3016, 2940, 1628, 1519, 1359, 1244, 1191, 756,
742 cm–1.
1H NMR (CD3OD): d = 7.91–7.85 (m, 3 H), 7.60–7.52 (m, 1 H),
4.39 (s, 3 H), 4.33 (s, 3 H).
13C NMR (CD3OD): d = 141.7, 135.7, 127.2, 122.7 (2 C), 122.4,
112.4, 37.3, 35.4.
HRMS-ESI: m/z calcd for C17H16BrN2O: 343.0446; found:
343.0444.
4-Hydroxy-1,2-dimethyl-2,4-dihydro-1H-spiro[cinnoline-3,2¢-
inden]-1¢(3¢H)-one (16)
Yellow solid; yield: 95 mg (65%); mp 188–190 °C.
IR (KBr): 3253, 3059, 2864, 2807, 1704, 1603, 1573, 1490, 1280,
1218, 1044, 747 cm–1.
EIMS: m/z (%) = 211, 213 (M+, 100), 132 (15).
HRMS-ESI: m/z calcd for C9H10BrN2: 225.0027; found: 225.0034
1H NMR (CDCl3): d = 7.74 (d, J = 7.72 Hz, 1 H, 7¢-H), 7.56 (ddd,
J = 7.63, 7.31, 1.08 Hz, 1 H, 5¢-H), 7.51 (d, J = 7.59 Hz, 1 H, 5-H),
7.36 (d, J = 7.63 Hz, 1 H, 4¢-H), 7.31 (dd, J = 7.72, 7.31 Hz, 1 H, 6¢-
H), 7.22 (ddd, J = 8.13, 7.50, 0.78 Hz, 1 H, 7-H), 6.82 (ddd,
J = 7.59, 7.50, 0.79 Hz, 1 H, 6-H), 6.53 (d, J = 8.13 Hz, 1 H, 8-H),
5.34 (s, 1 H, 4-H), 3.25 (d, J = 17.4 Hz, 1 H, 3¢-H), 3.14 [s, 3 H,
N(1)-CH3], 3.04 (d, J = 17.4 Hz, 1 H, 3¢-H), 2.66 [s, 3 H, N(2)-
CH3], 2.38 (br s, 1 H, OH).
13C NMR (100 MHz, CDCl3): d = 204.6 (C-1¢), 153.3 (C-7a¢), 142.2
(C-8a), 136.5 (C-3a¢), 135.6 (C-5¢), 128.5 (C-7), 127.3 (C-6¢), 126.9
(C-5), 126.4 (C-4¢), 124.4 (C-7¢), 121.4 (C-4a), 117.1 (C-6), 110.6
(C-8), 68.7 (C-3/C-2¢), 62.5 (C-4), 38.8 [N(1)-CH3], 35.1 [N(2)-
CH3], 34.3 (C-3).
Anal. Calcd for C9H10Br2N2: C, 35.33; H, 3.29; N, 9.15. Found: C,
35.58; H, 3.07; N, 9.47.
References
(1) Song, J. J.; Tan, Z.; Reeves, J. T.; Fandrick, D. R.; Yee, N.
K.; Senanayake, C. H. Org. Lett. 2008, 10, 877.
(2) Zhang, Y.-R.; He, L.; Wu, X.; Shao, P.-L.; Ye, S. Org. Lett.
2008, 10, 277.
(3) Phillips, E. M.; Reynolds, T. E.; Scheidt, K. A. J. Am. Chem.
Soc. 2008, 130, 2416.
(4) Sohn, S. S.; Bode, J. W. Angew. Chem. Int. Ed. 2006, 45,
6021, Angew. Chem. 2006, 118, 6167.
(5) Zeitler, K. Org. Lett. 2006, 8, 637.
(6) (a) Sohn, S. S.; Bode, J. W. Org. Lett. 2005, 7, 3873.
(b) Chan, A.; Scheidt, K. A. Org. Lett. 2005, 7, 905.
(7) Reynolds, N. T.; Read de Alaniz, J.; Rovis, T. J. Am. Chem.
Soc. 2004, 126, 9518.
MS-EI: m/z (%) = 294 (30), 279 (10), 108 (100).
HRMS-ESI: m/z calcd for C18H19N2O2: 295.1447; found: 295.1453.
Anal. Calcd for C18H18N2O2: C, 73.45; H, 6.16; N, 9.52. Found: C,
72.59; H, 5.36; N, 9.27.
(8) Chow, K. Y.-K.; Bode, J. W. J. Am. Chem. Soc. 2004, 126,
8126.
X-ray Crystal Structure Analysis of 16
Molecular formula: C18H18N2O2; MW: 294.34 g mol–1. A suitable
single crystal of the title compound was selected under a polariza-
tion microscope and mounted in a glass capillary (d = 0.3 mm). The
crystal structure was determined by X-ray diffraction analysis using
graphite monochromated MoKa radiation (0.71073 Å) [T = 223(2)
K], whereas the scattering intensities were collected with a single
crystal diffractometer (STOE IPDS II). The crystal structure was
solved by Direct Methods using SHELXS-97 and refined using al-
ternating cycles of least squares refinements against F2 (SHELXL-
97).29,30 All non-H atoms were located in Difference Fourier maps
and were refined with anisotropic displacement parameters. The H
positions were determined by a final Difference Fourier Synthesis.31
(9) (a) Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007,
107, 5606. (b) N-Heterocyclic Carbenes in Synthesis;
Nolan, S. P., Ed.; Wiley-VCH: Weinheim, 2006.
(c) Marion, N.; Diez-González, S.; Nolan, S. P. Angew.
Chem. Int. Ed. 2007, 46, 2988; Angew. Chem. 2007, 119,
3046. (d) Zeitler, K. Angew. Chem. Int. Ed. 2005, 44, 7506;
Angew. Chem. 2005, 117, 7674. (e) Enders, D.; Balensiefer,
T. Acc. Chem. Res. 2004, 37, 534.
(10) (a) Nair, V.; Sreekumar, V.; Bindu, S.; Suresh, E. Org. Lett.
2005, 7, 2297. (b) Nair, V.; Bindu, S.; Sreekumar, V.; Rath,
N. P. Org. Lett. 2003, 5, 665.
(11) (a) Enders, D.; Breuer, K.; Raabe, G.; Runsink, J.; Teles, J.
H.; Melder, J.-P.; Ebel, K.; Brode, S. Angew. Chem., Int. Ed.
Engl. 1995, 34, 1021; Angew. Chem. 1995, 107, 1119.
(b) Teles, J. H.; Melder, J.-P.; Ebel, K.; Schneider, R.;
Gehrer, E.; Harder, W.; Brode, S.; Enders, D.; Breuer, K.;
Raabe, G. Helv. Chim. Acta 1996, 79, 61. (c) Scholl, M.;
Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953.
(12) (a) Schmidt, A.; Beutler, A.; Albrecht, M.; Ramírez, F. J.
Org. Biomol. Chem. 2008, 6, 287. (b) Crabtree, R. H.
J. Organomet. Chem. 2006, 691, 3146. (c) Schmidt, A.;
Habeck, T.; Merkel, L.; Mäkinen, M.; Vainiotalo, P. Rapid
Commun. Mass Spectrom. 2005, 19, 2211. (d) Schmidt, A.;
Habeck, T. Lett. Org. Chem. 2005, 2, 37. (e) Voutchkova,
A. M.; Appelhans, L. N.; Chianese, A. R.; Crabtree, R. H.
J. Am. Chem. Soc. 2005, 127, 17624. (f) Katritzky, A. R.;
Faid-Allah, H. M. Synthesis 1983, 149. (g) Quast, H.;
Schmitt, E. Liebigs Ann. Chem. 1970, 732, 43.
Compound 16 crystallized in the space group P21/c (monoclinic),
lattice parameters a = 11.815(1) Å, b = 10.113(1) Å, c = 13.162(2)
Å, b = 113.72(1)°, V = 1439.8(3) Å3, Z = 4, dcalc. = 1.358 g cm–3,
m(MoKa) = 0.090 mm–1, index ranges: –14 £ h £ 14, –12 £ k £ 10,
–15 £ l £ 15; F(000) = 624 using 2538 independent reflections and
267 parameters. R1 = 0.0498, wR2 = 0.1314 [I > 2s(I)], goodness of
fit on F2 = 1.117, residual electron density = 0.312 and –0.350 e Å–3.
Dehalogenation Reactions with 1; General Procedure
Under N2, samples of 1,2-dimethyl-indazolium-3-carboxylate (1;
110 mg, 0.55 mmol) and the corresponding dibromides (see
Tables 1, 0.5 mmol) were suspended in anhyd MeCN (4 mL). These
suspensions were heated at reflux for 45 min. After cooling, the sol-
vent was distilled off in vacuo. The residue was stirred in PE–
EtOAc (2:1) and the insoluble by-products were filtered off. The fil-
trate was finally chromatographed (silica gel, PE–EtOAc) and the
products were isolated by evaporation of the solvent. All the prod-
ucts 18a–g, 21, 23, and 25 were identified by comparison of their
analytical and spectral data with the authentic samples. During the
dehalogenations, 3-bromo-1,2-dimethylindazolium bromide (19)
(13) Schmidt, A.; Beutler, A.; Habeck, T.; Mordhorst, T.;
Snovydovych, B. Synthesis 2006, 1882.
Synthesis 2008, No. 17, 2798–2804 © Thieme Stuttgart · New York