F. Blasberg et al. / Journal of Organometallic Chemistry 696 (2011) 3593e3600
3599
3
4
3.2. Synthesis of 1(Ph)
1H NMR (250.1 MHz, d6-DMSO)
d
5.81 (dd, JHH ¼ 8.2, JHH ¼ 1.7, 1
H; HQ-H6), 5.99 (d, 4JHH ¼ 1.7, 1 H; HQ-H2), 6.69 (vt, 3JHH ¼ 2.2, 2 H;
pz-H4), 6.81 (d, 3JHH ¼ 8.2, 1 H; HQ-H5), 8.05 (d, 3JHH ¼ 2.2, 2 H; pz-
H3/5), 8.42 (s, 1 H; CH), 8.49 (d, 3JHH ¼ 2.2, 2 H; pz-H3/5), 9.27, 9.43
3-Phenylpyrazole (2.00 g, 13.87 mmol) as a solid was added to
a stirred slurry of NaH (0.33 g, 13.87 mmol) in THF (60 mL) at r.t.
After 30 min SOCl2 (0.50 mL, 0.83 g, 6.94 mmol) was added in one
portion via syringe and the resulting mixture stirred at r.t. for
5 min. After addition of 3,4-dihydroxybenzaldehyde (0.96 g,
6.94 mmol) and pyridine (5.60 mL, 4.78 g, 60.40 mmol), the reac-
tion mixture was kept at reflux temperature for 16 h. H2O (50 mL)
was added and the aqueous phase extracted into CH2Cl2
(3 ꢂ 50 mL). The combined organic extracts were washed with
brine, dried over MgSO4, filtered, and the filtrate was evaporated to
dryness in vacuo. The crude product was purified by column
chromatography (silica gel; CHCl3/EtOAc 1:1). All product-
containing fractions were concentrated by rotary evaporation at
40 ꢁC and upon cooling to r.t. colorless 1(Ph) precipitated, which
was isolated by filtration and washed with Et2O. Yield: 1.53 g (54%).
Rf ¼ 0.63 (silica gel, CHCl3/EtOAc 1:1). 1H NMR (400.1 MHz, d6-
(2 ꢂ s, 2 ꢂ 1 H; OH). 13C NMR (62.9 MHz, d6-DMSO)
d 74.1 (Cpz2),
107.3 (pz-C4), 112.5 (HQ-C2), 115.8 (HQ-C6), 116.2 (HQ-C5), 125.8
(HQ-C1), 135.8, 143.9 (pz-C3,5), 145.8, 146.6 (HQ-C3,4). ESIeMS m/z
(%) 433 (100) [M ꢀ H]ꢀ. Anal. Calcd for C13H12Cl2N4O2Pd ꢂ 0.5 H2O
(433.59 þ 9.00): C 35.28, H 2.96, N 12.66. Found C 35.39, H 2.70, N
12.58. IR (KBr): v (cmꢀ1) 1605 (w), 1518 (s), 1458 (w), 1326 (s), 1214
~
(m), 1183 (m), 1150 (w), 1118 (s), 1082 (m), 1074 (s), 1007 (w), 833
(w), 790 (s), 767 (s), 620 (m).
3.5. Reaction of 1(Ph) with PdCl2
1(Ph) (35 mg, 0.086 mmol) and (MeCN)2PdCl2 (22 mg,
0.086 mmol) in MeCN (3 mL) were heated to reflux for 40 min. The
reaction mixture was evaporated to dryness and redissolved in
boiling MeCN. Cooling to r.t. afforded orange plates of 3(Ph) suit-
able for X-ray diffraction. Yield 15 mg (38%). 1H NMR (250.1 MHz,
3
4
DMSO)
d
¼ 6.48 (dd, JHH ¼ 8.3, JHH ¼ 2.0, 1 H; HQ-H6), 6.66 (d,
3
4JHH ¼ 2.0, 1 H; HQ-H2), 6.76 (d, JHH ¼ 8.3, 1 H; HQ-H5), 6.84 (d,
3JHH ¼ 2.5, 2 H; pz-H4), 7.31 (m, 2 H; Ph-H4), 7.41 (m, 4 H; Ph-H3),
CDCl3)
d
¼ 6.48 (vt, 3JHH ¼ 2.4, 2 H; pz-H4), 7.39e7.56 (m, 10 H; Ph-
3
H), 8.05 (vt, JHH ¼ 2.4, 2 H; pz-H5), 11.84 (s, 2 H; NH). 13C NMR
3
7.82 (m, 4 H; Ph-H2), 7.91 (s, 1 H; CH), 7.94 (d, JHH ¼ 2.5, 2 H; pz-
H5), 9.15 (bs, 2 H; OH). 13C NMR (100.6 MHz, d6-DMSO)
d
¼ 76.7
(62.9 MHz, CDCl3)
d
¼ 104.0 (pz-C4), 126.0, 127.5, 129.5, 130.1 (Ph-
(Cpz2), 103.5 (pz-C4), 114.4 (HQ-C2), 115.5 (HQ-C5), 118.2 (HQ-C6),
125.3 (Ph-C2), 127.2 (HQ-C1), 127.8 (Ph-C4), 128.7 (Ph-C3), 131.9
(pz-C5), 132.8 (Ph-C1), 145.3, 146.1 (HQ-C3,4), 151.0 (pz-C3).
ESIeMS: m/z (%) 263 (67) [M ꢀ Phpz]ꢀ, 408 (100) [M ꢀ H]ꢀ. Anal.
Calcd (%) for C25H20N4O2 (408.45): C 73.51, H 4.94, N 13.72. Found: C
73.22, H 4.86, N 13.67.
C), 143.5 (pz-C5), 144.8 (pz-C3). ESIeMS: m/z (%) 321 (15) [(Phpz)
PdCl2]ꢀ, 464 (5) [M ꢀ H]ꢀ. Anal. Calcd (%) for C18H16Cl2N4Pd
(465.67): C 46.43, H 3.46, N 12.03. Found: C 46.24, H 3.48, N 12.12.
3.6. Reaction of 1(tBu) with PdCl2
1(tBu) (50 mg, 0.136 mmol) and (MeCN)2PdCl2 (35 mg,
0.136 mmol) were combined in MeCN (2 mL) and heated to reflux
for 2.5 h. The solution was concentrated by rotary evaporation.
Upon cooling to r.t. cocrystals of 3(tBu) ꢂ 0.75 MeCN suitable for
X-ray diffraction formed along with an oily residue. For purification
the whole material was dissolved in hot MeCN and the resulting
solution cooled to ꢀ30 ꢁC for 2 days. Orange needles of analytically
pure 3(tBu) were separated from the mother liquor and dried
3.3. Synthesis of 1(tBu)
Neat 3-tert-butylpyrazole (3.17 g, 25.52 mmol) was added to
a stirred suspension of NaH (0.61 g, 25.52 mmol) in THF (70 mL).
Stirring was continued for 30 min, then neat SOCl2 (0.93 mL, 1.52 g,
12.76 mmol) was added in one portion via syringe. After treatment
with 3,4-dihydroxybenzaldehyde (1.76 g, 12.76 mmol) and pyridine
(10.30 mL, 10.09 g, 127.59 mmol), the reaction mixture was kept at
reflux temperature for 16 h. H2O (50 mL) was added and the
aqueous phase extracted into CH2Cl2 (3 ꢂ 50 mL). The combined
organic extracts were dried over MgSO4, filtered, and the filtrate
was evaporated to dryness in vacuo. The crude product was purified
by column chromatography (silica gel; hexane/EtOAc 1:1). Yield:
2.13 g (45%). Single crystals were grown by layering an EtOAc
solution of 1(tBu) with hexane. Rf ¼ 0.48 (silica gel, hexane/EtOAc
under a vacuum. Yield 26 mg (45%). 1H NMR (300.0 MHz, CDCl3)
3
d
¼ 1.31 (s, 18 H; CH3), 6.08 (vt, JHH ¼ 2.4, 2 H; pz-H4), 7.91 (vt,
3JHH ¼ 2.4, 2 H; pz-H5), 11.33 (s, 2 H; NH). 13C NMR (75.4 MHz,
CDCl3)
d
¼ 29.9 (CCH3), 31.6 (CCH3), 103.0 (pz-C4), 142.5 (pz-C5),
155.0 (pz-C3). ESIeMS: m/z (%) 213 (96) [M ꢀ 2H]ꢀ, 301 (100)
[M ꢀ H ꢀ tBupzH]ꢀ, 426 (10) [M ꢀ H]ꢀ. Anal. Calcd (%) for
C14H24Cl2N4Pd (425.69): C 39.50, H 5.68, N 13.16. Found: C 39.10, H
5.36, N 13.36.
1:1). 1H NMR (250.1 MHz, d6-DMSO)
d
1.23 (s, 18 H; CH3), 6.23 (m, 3
4
H; pz-H4, HQ-H6), 6.42 (d, JHH ¼ 1.7, 1 H; HQ-H2), 6.68 (d,
3JHH ¼ 8.2, 1 H; HQ-H5), 7.61 (m, 3 H; pz-H5, CH), 9.05 (bs, 2 H; OH).
3.7. Crystal structure determination
13C NMR (62.9 MHz, d6-DMSO)
d 30.4 (CH3), 31.7 (CCH3), 76.4
Data collection: STOE IPDS II two-circle diffractometer, graphite-
(Cpz2), 102.2 (pz-C4), 114.2 (HQ-C2), 115.2 (HQ-C5), 117.7 (HQ-C6),
128.5 (HQ-C1), 130.0 (pz-C5), 145.1, 145.7 (HQ-C3,4), 161.2 (pz-C3).
ESIeMS: m/z (%) 245 (100) [M ꢀ tBupz]þ, 369 (56) [M þ H]þ, 739
(11) [M2 þ H]þ. Anal. Calcd (%) for C21H28N4O2 (368.47): C 68.45, H
ꢀ
monochromated MoKa radiation
(l
¼ 0.71073 A, T ¼ 173(2) K).
Empirical absorption corrections were performed using MULABS
option in PLATON [26]. The structures were solved by direct
methods using the program SHELXS [27] and refined against F2
with full-matrix least-squares techniques using the program
SHELXL-97 [28]. All non-hydrogen atoms were refined with
anisotropic displacement parameters. Hydrogen atoms were
located by difference Fourier synthesis and refined using a riding
model.
7.66, N 15.21. Found: C 68.93, H 7.46, N 15.18. IR (KBr): v (cmꢀ1) 3121
~
(m), 2959 (m), 1610 (s), 1440 (m), 1294 (m), 1271 (s), 1195 (m), 1119
(s), 1069 (s), 1057 (m), 809 (s), 793 (m).
3.4. Synthesis of 2(H)
In MeCN (20 mL) 1(H) (0.47 g, 1.83 mmol) and (cod)PdCl2
(0.55 mg, 1.93 mmol) were suspended and heated to reflux for 3 h.
After cooling to r.t. all volatiles were removed in vacuo and the
residue was washed with CH2Cl2 until the filtrate was colorless to
yield a yellow solid. Single crystals of 2(H) were obtained by
layering a saturated THF solution with hexane. Yield: 0.69 g (87%).
Acknowledgments
M.W. is grateful to the “Deutsche Forschungsgemeinschaft”
(DFG) for financial support (TR 49). F.B. wishes to thank the “Fonds
der Chemischen Industrie” (FCI) for a Ph.D. grant.