Synthesis, characterization and antitumor activity of novel amide derivatives containing ferrocenyl pyrazol-moiety

Article abstract of DOI:10.1016/j.jorganchem.2012.02.001

A series of novel 2-(5-ferrocenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)-N- amide derivatives (1-38) were prepared. The compounds were characterized by ¹H NMR, ¹³C NMR, IR, mass spectroscopy and element analysis. Compounds 19 and 30 we

Full text of DOI:10.1016/j.jorganchem.2012.02.001

Journal of Organometallic Chemistry 706-707 (2012) 113e123
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Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis, characterization and antitumor activity of novel amide derivatives
containing ferrocenyl pyrazol-moiety
,
Xian-Feng Huang a, Jian-Feng Tang b, Jun-Ling Ji a, Xiao-Liang Wang b, Ban-Feng Ruan b
*
a School of Chemistry & Chemical Engineering, Changzhou University, Changzhou 213164, PR China
b School of Medical Engineering, Hefei University of Technology, Hefei 230009, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of novel 2-(5-ferrocenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)-N-amide derivatives (1e38) were
prepared. The compounds were characterized by 1H NMR, 13C NMR, IR, mass spectroscopy and element
analysis. Compounds 19 and 30 were also gave crystals suitable for X-ray structural analysis. Biological
evaluation of all the compounds were performed in the human prostatic carcinoma cell line (PC-3) and
human mammary carcinoma cell line (Bcap-37) using the MTT method. Among them, compound 10
exhibited comparable in vitro antitumor activity to the positive control 5-Fluorouracil (5-FU) and
cisplatin.
Received 12 September 2011
Received in revised form
27 January 2012
Accepted 1 February 2012
Keywords:
Ferrocene-containing acetic acid
Amide derivative
Ó 2012 Elsevier B.V. All rights reserved.
X-ray structural analysis
Antitumor activity
1. Introduction
tamoxifen, significantly augments the anticancer activity of
tamoxifen [19]. Ferricenium salts, besides their antiproliferative
Prompted by the initial success of platinum chemotherapeutic
metallopharmaceuticals, attention was first shifted to non-
platinum chemotherapeutics starting from the basic cisplatin
framework, with the aim to optimize the efficiency of such drugs
and to avoid serious side-effects caused by platinum chemothera-
peutics [1e4]. Among these, organometallic compounds, which are
defined as metal complexes containing at least one direct, covalent
metal-carbon bond, have attracted special attention recently and
been found to be promising anticancer drug candidates [5e7].
Organometallic medicinal chemistry is becoming one of the most
promising developments in bioorganometallic chemistry [8].
As the first organometallic compound for which antiproliferative
properties were reported [9], the antitumor activities of ferrocene-
containing compounds themselves were extensively studied in vitro
and in vivo [10e12]. Unique properties such as the similarities in
aromaticity, lipophilicity, stability, low toxicity and unusual redox
activity recommend ferrocene for incorporation in drug molecules
[13]. Several structural modification of established drugs with fer-
rocenyl moiety have been reported, such as ferrocene fluconazole
[14], ferrocene aspirin [15], the antimalarial drugs chloroquine
(termed ferroquine) [16], mefloquine [17], and artemisinin [18]. The
ferrocenyl moiety in ferrocifen, which is a ferrocene conjugated
activity also display DNA-cleaving activity and DNA synthesis
inhibitory effect [20]. Recently therapeutic synergism of the anti-
tumor activity of a combination of ferrocenylmethyl thymine with
the well known antitumor drug cyclophosphamide against Ca755
was demonstrated [21]. Accordingly, using ferrocenyl-containing
derivatives as medicines and other chemotherapeutants has long
been recognized as an attractive way [22,23].
Recently, a ferrocene-containing derivative 3-trifluoromethyl-5-
ferrocenyl -pyrazol-1-yl-acetic acid (LCOOH) and three organo-
tin(IV) carboxylate derivatives [Ph4Sn2O(OCH3)(OOCL)]2, [BuS-
nO(OOCL)]6 and [Bu4Sn2O(OOCL2)2] had been synthesized in our
lab [24]. Their antitumor activities were also evaluated against
three cancer cell lines. In continuation with our recent studies on
ferrocene derivatives, we have focused our attention to synthesize
a series of novel amide derivatives (1e38) using the same
ferrocene-containing acetic acid to extend the structureeactivity
relationships (SAR) study. We also describe the crystal structures
of compounds 19 and 30 featuring the amide derivatives that
derived from primary and secondary amines, respectively.
2. Experimental
2.1. General
All the NMR spectra were recorded on a Bruker DRX 400
* Corresponding author. Tel.: þ86 551 2901771.
E-mail address: bf_ruan@163.com (B.-F. Ruan).
model Spectrometer in CDCl3. Chemical shifts (d
) for 1H NMR and
0022-328X/$ e see front matter Ó 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2012.02.001

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X.-F. Huang et al. / Journal of Organometallic Chemistry 706-707 (2012) 113e123
13C NMR spectra were reported in parts per million to residual
solvent protons. Melting points were measured on a Boetius
micro melting point apparatus. The ESIeMS spectra were recor-
ded on a Mariner System 5304 Mass spectrometer. Carbon,
hydrogen and nitrogen assays were carried out with a CHN-O-
Rapid instrument and were within ꢀ0.4% of the theoretical
values. TLC was run on the silica gel coated aluminum sheets
(Silica Gel 60 GF254, E. Merk, Germany) and visualized in UV
light (254 nm).
2.2.2. N-(4-methoxyphenyl)-2-(5-ferrocenyl-3-(trifluoromethyl)-
1H-pyrazol-1-yl)acetamide (2)
Brown solid (0.450 g, 93.1% yield). Mp.: 121e123 ꢁC 1H NMR
(400 MHz, CDCl3)
d (ppm): 3.81 (s, 3H), 4.21 (s, 5H), 4.44 (s, 2H),
4.58 (s, 2H), 5.18 (s, 2H), 6.66 (s, 1H), 6.88 (d, 2H, J ¼ 9.0 Hz), 7.39 (d,
2H, J ¼ 9.0 Hz), 7.95 (s, 1H). 13C NMR (400 MHz, CDCl3)
d (ppm):
54.0, 55.5, 68.7, 69.8, 70.0, 72.2, 104.6, 104.6, 114.3, 121.9, 129.9,
145.4, 157.0, 164.3. MS (ESI): m/z 484 ([M þ H]þ). Anal. Calc for
C23H20F3FeN3O2: C, 57.16; H, 4.17; O, 6.62%. Found: C, 58.38; H, 4.16;
O, 6.64%. IR (KBr, cmꢂ1):
n
¼ 3279(m), 1662(s), 1552(s), 1504(s),
1408(m), 1233(s), 1130(s), 965(m), 825(s), 715(m).
2.2. Synthesis
2.2.3. N-(3-methoxyphenyl)-2-(5-ferrocenyl-3-(trifluoromethyl)-
1H-pyrazol-1-yl)acetamide (3)
Acetylferrocene, ethyl trifluoroacetate, ethyl bromoacetate,
EDC.HCl, HOBt, primary amines and secondary amines were
purchased from SigmaeAldrich. The synthesis of all the compounds
(1e38) was performed in a manner as outlined in Scheme 1. The
intermediates 4,4,4-trifluoro-1-ferrocenylbutane-1,3-dione (B), 5-
ferrocenyl-3-(trifluoromethyl)-1H-pyrazole(C) and 2-(5-ferrocenyl
-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetic acid (D) were synthe-
sized according to the established methods [24,25].
A solution of D (0.454 mg, 1.2 mmol), EDC$HCl (0.216 g,
1.2 mmol) and HOBt (0.135 g, 1 mmol) in 25 mL of CH2Cl2 was
stirred at room temperature for 0.5 h. Then, a CH2Cl2 solution
(25 mL) of substituted primary or secondary amines (1 mmol) was
added dropwise, respectively. The reaction mixture was stirred
overnight at room temperature and the solvent was evaporated.
Column chromatography of the crude mixture on silica gel using
petroleum ether/ethyl acetate as eluent to afford the target
compounds 1e38, see Table 1 and Table 2.
Brown solid (0.398 g, 82.4% yield). Mp.: 136e138 ꢁC 1H NMR
(400 MHz, CDCl3)
d (ppm): 3.82 (s, 3H), 4.21 (s, 5H), 4.45 (s, 2H),
4.57 (s, 2H), 5.18 (s, 2H), 6.66 (s, 1H), 6.71 (d, 1H, J ¼ 8.4 Hz), 6.94 (d,
1H, J ¼ 8.0 Hz), 7.23 (d, 1H, J ¼ 8.0 Hz), 7.26 (s, 1H), 8.14 (s, 1H). 13C
NMR (400 MHz, CDCl3)
d (ppm): 54.0, 55.3, 68.7, 69.8, 70.0, 72.2,
104.6, 104.6, 105.8, 110.8, 112.1, 129.8, 138.1, 145.5, 160.1, 164.4. MS
(ESI): m/z 484 ([M þ H]þ). Anal. Calc for C23H20F3FeN3O2: C, 57.16;
H, 4.17; O, 6.62%. Found: C, 57.02; H, 4.18; O, 6.61%. IR (KBr, cmꢂ1):
n
¼ 3276(s), 3060(m), 1682(s), 1604(s), 1528(s), 1466(s), 1412(m),
1315(m), 1237(s), 1185(s), 1137(s), 1024(s), 973(s), 858(s), 753(s).
2.2.4. N-(2-methoxyphenyl)-2-(5-ferrocenyl-3-(trifluoromethyl)-
1H-pyrazol-1-yl)acetamide (4)
Brown solid (0.365 g, 75.6% yield). Mp.: 131e133 ꢁC 1H NMR
(400 MHz, CDCl3)
d (ppm): 3.72 (s, 3H), 4.06 (s, 5H), 4.33 (s, 2H),
4.48 (s, 2H), 5.11 (s, 2H), 6.58 (s, 1H), 6.77 (d, 1H, J ¼ 8.0 Hz),
6.86e6.91 (m, 1H), 6.96e7.00 (m, 1H), 8.32 (d, 1H, J ¼ 8.0 Hz), 8.52
2.2.1. N-Phenyl-2-(5-ferrocenyl-3-(trifluoromethyl)-1H-pyrazol-1-
yl)acet-amide (1)
(s, 1H). 13C NMR (400 MHz, CDCl3)
d (ppm): 54.5, 55.4, 68.6, 69.9,
Brown solid (0.408 g, 90.2% yield). Mp.: 151e153 ꢁC 1H NMR
70.1, 72.1, 104.5, 104.5, 115.0, 119.4, 121.1, 124.5, 126.9, 145.3, 148.0,
164.4. MS (ESI): m/z 484 ([M þ H]þ). Anal. Calc for C23H20F3FeN3O2:
C, 57.16; H, 4.17; O, 6.62%. Found: C, 57.34; H, 4.06; O, 6.64%. IR (KBr,
(400 MHz, CDCl3) d (ppm): 4.18 (s, 5H), 4.42 (s, 2H), 4.55 (s, 2H), 5.17
(s, 2H), 6.63 (s, 1H), 7.12e7.15 (m, 1H), 7.31e7.35 (m, 2H), 7.47 (d,
cmꢂ1):
n
¼ 3268(m), 1682(s), 1607(m), 1538(s), 1460(m), 1322(m),
J ¼ 8.4 Hz, 2H), 8.16 (s,1H). 13C NMR (400 MHz, CDCl3)
d (ppm): 54.1,
1230(s), 1134(s), 1027(s), 979(m), 828(m), 756(s).
68.7, 69.8, 70.1, 72.1, 104.6, 104.7, 120.0, 125.1, 129.2, 136.8, 145.7,
164.4. MS (ESI): m/z 454 ([M þ H]þ). Anal. Calc for C22H18F3FeN3O:
C, 58.30; H, 4.00; O, 3.53%. Found: C, 58.12; H, 4.02; O, 3.54%. IR
2.2.5. N-(3,5-methoxyphenyl)-2-(5-ferrocenyl-3-(trifluoromethyl)-
1H-pyrazol-1-yl)acetamide (5)
(KBr, cmꢂ1):
n
¼ 3270(m), 1679(s), 1604(s), 1549(s), 1508(m),
Brown solid (0.372 g, 72.4% yield). Mp.: 96e97 ꢁC 1H NMR
1439(s),1412(s),1367(m),1312(m),1247(s),1218(s),1147(s),1120(s),
976(s), 808(m), 756(m).
(400 MHz, CDCl3)
d (ppm): 3.79 (s, 6H), 4.21 (s, 5H), 4.44 (s, 2H),
Scheme 1. Synthesis of compounds 1e38. (a) EtOH/Na, CF3COOC2H5; (b) EtOH, NH2NH2.H2O; (c) BrCH2COOC2H5, t-BuOK, CH3CN; (d) KOH, EtOH, H2O; (e) EDC$HCl, HOBt, CH2Cl2.
Figure(s)

X.-F. Huang et al. / Journal of Organometallic Chemistry 706-707 (2012) 113e123
Table 1 (continued )
115
Table 1
R1
Structures for compounds 1e26.
Structure
Comp. no.
Structure
Comp. no.
R1
1
2
17
18
3
4
19
20
5
6
7
21
22
23
24
8
25
26
9
10
4.57 (s, 2H), 5.16 (s, 2H), 6.27 (s, 1H), 6.66 (s, 1H), 6.72(s, 2H), 8.14 (s,
1H). 13C NMR (400 MHz, CDCl3)
(ppm): 54.1, 55.4, 68.7, 69.8, 70.1,
d
72.1, 97.3, 98.2, 104.6, 104.7, 138.5, 145.6, 161.1, 164.2. MS (ESI): m/z
514 ([M þ H]þ). Anal. Calc for C24H22F3FeN3O3: C, 56.16; H, 4.32; O,
9.35%. Found: C, 56.03; H, 4.33; O, 9.34%. IR (KBr, cmꢂ1):
11
12
n
¼ 3284(m), 1682(s), 1607(s), 1549(m), 1456(s), 1422(m), 1233(s),
1158(s), 1127(s), 1061(m), 825(m).
13
2.2.6. N-(3,4-methoxyphenyl)-2-(5-ferrocenyl-3-(trifluoromethyl)-
1H-pyrazol-1-yl)acetamide (6)
Brown solid (0.345 g, 67.3% yield). Mp.: 136e138 ꢁC 1H NMR
(400 MHz, CDCl3)
d (ppm): 3.87 (s, 3H), 3.90 (s, 3H), 4.21 (s, 5H),
4.45 (s, 2H), 4.58 (s, 2H), 5.19 (s, 2H), 6.66 (s, 1H), 6.84(d, 2H,
14
15
16
J ¼ 8.8 Hz), 7.28 (s, 1H), 8.04 (s, 1H). 13C NMR (400 MHz, CDCl3)
d
(ppm): 54.1, 56.0, 56.1, 68.7, 69.8, 70.0, 72.1, 104.6, 104.6, 104.8,
111.3, 112.1, 130.4, 145.5, 146.4, 149.2, 164.2. MS (ESI): m/z 514
([M þ H]þ). Anal. Calc for C24H22F3FeN3O3: C, 56.16; H, 4.32; O,
9.35%. Found: C, 56.36; H, 4.31; O, 9.38%. IR (KBr, cmꢂ1):
n
¼ 3261(m), 1679(s), 1556(m), 1511(s), 1415(m), 1247(s), 1113(s),
1024(m), 969(s), 797(m).
2.2.7. N-(2,5-methoxyphenyl)-2-(5-ferrocenyl-3-(trifluoromethyl)-
1H-pyrazol-1-yl)acetamide (7)
Brown solid (0.357 g, 69.5% yield). Mp.: 114e116 ꢁC 1H NMR
(400 MHz, CDCl3)
d (ppm): 3.77 (s, 3H), 3.81 (s, 3H), 4.15 (s, 5H),

116
X.-F. Huang et al. / Journal of Organometallic Chemistry 706-707 (2012) 113e123
(ESI): m/z 514 ([M þ H]þ). Anal. Calc for C24H22F3FeN3O3: C, 56.16;
Table 2
H, 4.32; O, 9.35%. Found: C, 56.32; H, 4.26; O, 9.33%. IR (KBr, cmꢂ1):
Structures for compounds 27e38.
n
¼ 3308(m), 3080(m), 1658(s), 1604(s), 1549(s), 1494(s), 1432(m),
Comp. no.
Structure
Comp. no.
Structure
1233(s), 1127(s), 973(s), 815(s), 739(m).
2.2.8. 2-(5-Ferrocenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)-N-
(3,4,5-trimethoxyphenyl)acetamide (8)
Brown solid (0.357 g, 83.5% yield). Mp.: 164e166 ꢁC 1H NMR
27
33
(400 MHz, CDCl3)
4.52 (s, 2H), 4.64 (s, 2H), 5.16 (s, 2H), 6.61 (s,1H), 6.77 (s, 2H), 8.12 (s,
1H). 13C NMR (400 MHz, CDCl3)
(ppm): 53.9, 56.0, 60.9, 68.8, 69.8,
d (ppm): 3.83 (s, 3H), 3.87 (s, 6H), 4.29 (s, 5H),
d
70.0, 72.3, 97.5, 104.6, 104.6, 133.2, 135.0, 145.6, 153.3, 164.2. MS
(ESI): m/z 544 ([M þ H]þ). Anal. Calc for C25H24F3FeN3O4: C, 55.27;
H, 4.45; O,11.78%. Found: C, 55.44; H, 4.44; O,11.76%. IR (KBr, cmꢂ1):
n
¼
3297(m), 1676(m), 1611(m), 1549(m), 1504(s), 1446(m),
1417(m), 1232(s), 1129(s), 969(m), 816(m).
28
34
2.2.9. N-(4-ethoxyphenyl)-2-(5-ferrocenyl-3-(trifluoromethyl)-1H-
pyrazol-1-yl)acetamide (9)
Brown solid (0.454 g, 91.2% yield). Mp.: 140e142 ꢁC 1H NMR
(400 MHz, CDCl3)
d
(ppm): 1.41 (t, 3H, J ¼ 7.2 Hz), 4.02 (q, 2H,
J ¼ 6.8 Hz), 4.21 (s, 5H), 4.45 (s, 2H), 4.58 (s, 2H), 5.17 (s, 2H), 6.65
(s, 1H), 6.87 (d, 2H, J ¼ 7.8 Hz), 7.37 (d, 2H, J ¼ 7.8 Hz), 7.93 (s, 1H).
13C NMR (400 MHz, CDCl3)
d (ppm): 14.8, 54.1, 63.7, 68.7, 69.8,
70.0, 71.8, 104.6, 104.6, 114.9, 121.8, 129.7, 145.4, 156.3, 164.2. MS
(ESI): m/z 498 ([M þ H]þ). Anal. Calc for C24H22F3FeN3O2: C,
57.97; H, 4.46; O, 6.43%. Found: C, 58.16; H, 4.38; O, 6.45%. IR
29
35
(KBr, cmꢂ1):
n
¼ 3256(m), 2946(m), 1679(s), 1604(s), 1545(s),
1442(s), 1388(m), 1243(s), 1134(s), 1041(s), 962(s), 917(m),
818(m), 743(s).
2.2.10. N-(2-ethoxyphenyl)-2-(5-ferrocenyl-3-(trifluoromethyl)-
1H-pyrazol-1-yl)acetamide (10)
Brown solid (0.352 g, 70.7% yield). Mp.: 136e138 ꢁC 1H NMR
(400 MHz, CDCl3)
d
(ppm): 1.34 (t, 3H, J ¼ 7.2 Hz), 4.03 (q, 2H,
J ¼ 7.2 Hz), 4.15 (s, 5H), 4.42 (s, 2H), 4.58 (s, 2H), 5.20 (s, 2H), 6.68 (s,
1H), 6.84 (d, 1H, J ¼ 8.0 Hz), 6.92e6.99 (m, 1H), 7.02e7.08 (m, 1H),
8.31 (s, 1H), 8.44 (d, 1H, J ¼ 7.6 Hz). 13C NMR (400 MHz, CDCl3)
30
36
d
(ppm): 15.0, 54.9, 64.3, 68.4, 69.8, 70.1, 72.0, 104.2, 104.2, 111.0,
115.1, 118.4, 120.9, 124.6, 145.3, 147.3, 164.5. MS (ESI): m/z 498
([M þ H]þ). Anal. Calc for C24H22F3FeN3O2: C, 57.97; H, 4.46; O,
6.43%. Found: C, 57.86; H, 4.47; O, 6.46%. IR (KBr, cmꢂ1):
n
¼ 3410(m), 3286(m), 1679(s), 1597(s), 1538(s), 1452(s), 1398(m),
1231(s), 1134(s), 1045(s), 973(s), 828(m), 753(s).
2.2.11. N-(4-acetylphenyl)-2-(5-ferrocenyl-3-(trifluoromethyl)-1H-
pyrazol-1-yl)acetamide (11)
31
37
Brown solid (0.442 g, 89.2% yield). Mp.: 48e49 ꢁC 1H NMR
(400 MHz, CDCl3)
d (ppm): 2.58 (s, 3H), 4.19 (s, 5H), 4.44 (s, 2H),
4.54 (s, 2H), 5.20 (s, 2H), 6.65 (s, 1H), 7.59 (d, 2H, J ¼ 8.4 Hz), 7.94
(d, 2H, J ¼ 8.4 Hz), 8.57 (s, 1H). 13C NMR (400 MHz, CDCl3)
d
(ppm): 26.5, 53.9, 68.8, 69.8, 70.1, 72.1, 104.7, 104.7, 119.2, 129.8,
141.3, 145.9, 164.6, 197.0. MS (ESI): m/z: 496 ([M þ H]þ). Anal.
Calc for C24H20F3FeN3O2: C, 58.20; H, 4.07; O, 6.46%. Found: C,
58.08; H, 4.08; O, 6.48%. IR (KBr, cmꢂ1):
n
¼ 3296(m), 3102(m),
32
38
1682(s), 1600(s), 1535(s), 1412(m), 1257(s), 1137(s), 973(m),
825(s).
2.2.12. 2-(5-Ferrocenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)-N-(4-
(trifluoromethoxy)phenyl)acetamide (12)
Brown solid (0.455 g, 84.6% yield). Mp.: 93e94 ꢁC 1H NMR
4.43 (s, 2H), 4.57 (s, 2H), 5.19 (s, 2H), 6.60 (d, 1H, J ¼ 8.4 Hz), 6.67 (s,
1H), 6.77 (d, 1H, J ¼ 8.4 Hz), 8.14 (s, 1H), 8.59 (s, 1H). 13C NMR
(400 MHz, CDCl3) d (ppm): 4.19 (s, 5H), 4.44 (s, 2H), 4.54 (s, 2H), 5.17
(s, 2H), 6.64 (s,1H), 7.00 (d,1H, J ¼ 8.0 Hz), 7.25 (d,1H, J ¼ 8.0 Hz), 7.33
(400 MHz, CDCl3)
d (ppm): 54.5, 55.8, 56.1, 68.5, 69.8, 70.0, 71.9,
(t,1H, J ¼ 8.4 Hz), 7.60 (s,1H), 8.40 (s,1H).13C NMR (400 MHz, CDCl3)
104.4, 104.5, 105.9, 109.1, 110.8, 127.5, 142.2, 145.3, 153.8, 164.4. MS
d (ppm): 53.8, 68.8, 69.6, 69.8, 70.1, 72.1, 104.7, 104.7, 112.8, 117.9,

X.-F. Huang et al. / Journal of Organometallic Chemistry 706-707 (2012) 113e123
117
130.1,138.3,145.7,149.6,164.5. MS (ESI): m/z 538.2 ([M þ H]þ). Anal.
2.2.18. N-(2-chlorophenyl)-2-(5-ferrocenyl-3-(trifluoromethyl)-1H-
pyrazol-1-yl)acetamide (18)
Brown solid (0.371 g, 76.1% yield). Mp.: 123e125 ꢁC 1H NMR
(400 MHz, CDCl3) (ppm): 4.18 (s, 5H), 4.44 (s, 2H), 4.56 (s, 2H),
Calc for C23H17F6FeN3O2: C, 51.42; H, 3.19; O, 5.96%. Found: C, 51.34;
H, 3.18; O, 5.97%. IR (KBr, cmꢂ1):
n
¼ 3276(s), 3070(m), 1672(s),
1607(s), 1562(s), 1247(s), 1151(s), 974(m), 804(s), 695(m).
d
5.23 (s, 2H), 6.88 (s, 1H), 7.06e7.10 (m, 1H), 7.28e7.32 (m, 1H), 7.37
(d, 1H, J ¼ 8.0 Hz), 8.45 (d, 1H, J ¼ 8.0 Hz), 8.58 (s, 1H). 13C NMR
2.2.13. 2-(5-Ferrocenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)-N-(o-
tolyl)acetamide (13)
(400 MHz, CDCl3)
d (ppm): 54.3, 68.6, 69.9, 70.1, 71.9, 104.8, 104.8,
Brown solid (0.442 g, 89.2% yield). Mp.: 178e180 ꢁC 1H NMR
119.0, 121.1, 125.4, 127.7, 129.2, 133.9, 145.6, 164.7. MS (ESI): m/z 489
([M þ H]þ). Anal. Calc for C22H17ClF3FeN3O: C, 54.18; H, 3.51; O,
3.28%. Found: C, 54.30; H, 3.50; O, 3.29%. IR (KBr, cmꢂ1):
(400 MHz, CDCl3)
d (ppm): 2.14 (s, 3H), 4.22 (s, 5H), 4.46 (s, 2H),
4.59 (s, 2H), 5.24 (s, 2H), 6.66 (s, 1H), 7.06e7.10 (m, 1H), 7.18 (d, 1H,
J ¼ 7.6 Hz), 7.23e7.26 (m,1H), 8.07 (d,1H, J ¼ 8.0 Hz), 8.10 (s,1H). 13C
n
¼ 3266(m), 1672(s), 1542(s), 1439(m), 1415(m), 1158(m), 1123(s),
NMR (400 MHz, CDCl3)
d
(ppm): 17.2, 54.2, 68.7, 69.8, 70.1, 72.0,
973(m), 794(m), 739(m).
104.7, 104.7, 121.4, 125.2, 126.9, 127.7, 130.6, 135.2, 145.5, 164.3. MS
(ESI): m/z 468 ([M þ H]þ). Anal. Calc for C23H20F3FeN3O: C, 59.12; H,
4.31; O, 3.42%. Found: C, 59.00; H, 4.32; O, 3.44%. IR (KBr, cmꢂ1):
2.2.19. N-(3-chlorophenyl)-2-(5-ferrocenyl-3-(trifluoromethyl)-1H-
pyrazol-1-yl)acetamide (19)
n
¼ 3338(m), 1655 (s), 1607(s), 1552(s), 1480(s), 1408(m), 1302(s),
Brown solid (0.392 g, 80.4% yield). Mp.: 162e164 ꢁC 1H NMR
1227(s), 1117(s), 976(s), 904(m), 821(s).
(400 MHz, CDCl3)
(s, 2H), 6.66 (s,1H), 7.12e7.16 (m,1H), 7.27 (d,1H, J ¼ 8.0 Hz), 7.69 (s,
1H), 8.27 (s,1H).13C NMR (400 MHz, CDCl3)
(ppm): 54.0, 68.7, 69.8,
d (ppm): 4.22 (s, 5H), 4.46 (s, 2H), 4.56 (s, 2H), 5.19
2.2.14. 2-(5-Ferrocenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)-N-
(m-tolyl)acetamide (14)
d
70.1, 71.8, 104.7, 104.7, 117.9, 120.1, 125.1, 130.1, 134.9, 138.0, 145.6,
164.4. MS (ESI): m/z 488 ([M þ H]þ). Anal. Calc for C22H17ClF3FeN3O:
C, 54.18; H, 3.51; O, 3.28%. Found: C, 54.33; H, 3.52; O, 3.27%. IR (KBr,
Brown solid (0.442 g, 89.2% yield). Mp.: 158e160 ꢁC 1H NMR
(400 MHz, CDCl3)
d (ppm): 2.36 (s, 3H), 4.24 (s, 5H), 4.47 (s, 2H),
4.61 (s, 2H), 5.17 (s, 2H), 6.63 (s, 1H), 6.97 (d, 1H, J ¼ 6.8 Hz), 7.22 (d,
cmꢂ1):
n
¼ 3214(m), 1669(s), 1590(m), 1528(s), 1398(m), 1298(m),
1H, J ¼ 8.0 Hz), 7.24e7.26 (m, 1H), 7.33 (s, 1H), 8.01 (s, 1H). 13C NMR
1195(m), 1127(s), 973(s), 794(m), 743(m).
(400 MHz, CDCl3)
d (ppm): 20.4, 53.1, 67.7, 68.8, 69.0, 71.1, 103.6,
103.6,116.1,119.6,124.9, 127.9, 135.7,138.1,144.4,163.3. MS (ESI): m/
z 468 ([M þ H]þ). Anal. Calc for C23H20F3FeN3O: C, 59.12; H, 4.31; O,
3.42%. Found: C, 59.00; H, 4.32; O, 3.44%. IR (KBr, cmꢂ1):
2.2.20. N-(4-bromophenyl)-2-(5-ferrocenyl-3-(trifluoromethyl)-
1H-pyrazol-1-yl)acetamide (20)
Brown solid (0.504 g, 94.7% yield). Mp.: 151e153 ꢁC 1H NMR
n
¼ 3296(m), 1676(s), 1618(s), 1566(s), 1494(m), 1415(m), 1302(s),
(400 MHz, CDCl3)
(s, 2H), 6.66 (s, 1H), 7.40 (d, 2H, J ¼ 9.0 Hz), 7.46 (d, 2H, J ¼ 9.0 Hz),
8.24 (s, 1H). 13C NMR (400 MHz, CDCl3)
(ppm): 52.9, 67.7, 68.8,
d (ppm): 4.21 (s, 5H), 4.46 (s, 2H), 4.56 (s, 2H), 5.18
1254(s), 1120(s), 791(s).
d
2.2.15. N-(3,5-dimethylphenyl)-2-(5-ferrocenyl-3-
(trifluoromethyl)-1H-pyrazol-1-yl)acetamide (15)
69.1, 71.0, 103.7, 103.7, 116.7, 120.4, 131.1, 134.9, 144.6, 163.3. MS
(ESI): m/z 533 (M þ H]þ). Anal. Calc for C22H17BrF3FeN3O: C, 49.66;
H, 3.22; O, 3.01%. Found: C, 49.58; H, 3.21; O, 3.02%. IR (KBr, cmꢂ1):
Brown solid (0.421 g, 87.4% yield). Mp.: 151e153 ꢁC 1H NMR
(400 MHz, CDCl3)
2H), 5.16 (s, 2H), 6.66 (s, 1H), 6.80(s, 1H), 7.11 (s, 2H), 7.93 (s, 1H). 13C
NMR (400 MHz, CDCl3) (ppm): 21.3, 54.2, 68.7, 69.8, 70.0, 72.2,104.6,
d
(ppm): 2.31 (s, 6H), 4.20 (s, 5H), 4.44 (s, 2H), 4.57 (s,
n
¼ 3266(m), 3152(m), 1604(s), 1682(s), 1614(s), 1549(s), 1484(s),
1404(s), 1312(s), 1250(s), 1141(s), 973(m), 818(s), 732(m).
d
104.6, 117.7, 126.8, 136.6, 138.9, 145.4, 164.4. MS (ESI): m/z 482
([M þ H]þ). Anal. Calc for C24H22F3FeN3O: C, 59.89; H, 4.61; O, 3.32%.
2.2.21. N-(4-fluorophenyl)-2-(5-ferrocenyl-3-(trifluoromethyl)-1H-
pyrazol-1-yl)acetamide (21)
Found:C, 59.78;H, 4.62;O, 3.34%. IR (KBr, cmꢂ1):
n
¼ 3308(m),1671(s),
Brown solid (0.430 g, 91.2% yield). Mp.: 95e97 ꢁC 1H NMR
1537(s), 1497(s), 1403(m), 1258(s), 1115(s), 961(s), 785(s), 703(m).
(400 MHz, CDCl3)
5.19 (s, 2H), 6.66 (s, 1H), 7.04 (t, 2H, J ¼ 8.4 Hz), 7.46 (dd, 2H, J ¼ 5.2,
8.4 Hz), 8.19 (s, 1H). 13C NMR (400 MHz, CDCl3)
(ppm): 53.9, 68.7,
d (ppm): 4.21 (s, 5H), 4.45 (s, 2H), 4.56 (s, 2H),
2.2.16. 2-(5-Ferrocenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)-N-(3-
(trifluoromethyl)phenyl)acetamide (16)
d
69.8, 70.1, 72.0, 104.7, 104.7, 115.7, 115.9, 121.8, 132.9, 145.6, 164.3.
MS (ESI): m/z 472 ([M þ H]þ). Anal. Calc for C22H17F4FeN3O: C,
56.07; H, 3.64; O, 3.40%. Found: C, 55.97; H, 3.65; O, 3.41%. IR (KBr,
Brown solid (0.350 g, 67.2% yield). Mp.: 96e98 ꢁC 1H NMR
(400 MHz, CDCl3) d (ppm): 4.22 (s, 5H), 4.46 (s, 2H), 4.59 (s, 2H), 5.20
(s, 2H), 6.66 (s, 1H), 7.02 (d, 1H, J ¼ 8.0 Hz), 7.27 (d, 1H, J ¼ 8.0 Hz),
cmꢂ1):
n
¼ 3236(s), 3102(s), 1658(s), 1559(s), 1500(s), 1404(m),
7.36e7.38 (m,1H), 7.63 (s,1H), 8.44 (s,1H).13C NMR (400 MHz, CDCl3)
1223(s), 1127(m), 969(s), 828(s), 725(s).
d
(ppm): 53.9, 68.7, 69.8, 70.1, 71.9, 104.8, 104.8, 112.8, 117.1, 117.9,
130.2, 138.3, 144.1, 145.8, 149.6, 164.5. MS (ESI): m/z 522 ([M þ H]þ).
2.2.22. N-Cyclopropyl-2-(5-ferrocenyl-3-(trifluoromethyl)-1H-
pyrazol-1-yl)acetamide (22)
Anal. Calc for C23H17F6FeN3O: C, 53.00; H, 3.29; O, 3.07%. Found: C,
53.17; H, 3.28; O, 3.08%. IR (KBr, cmꢂ1):
n
¼ 3328(s), 2946(m),1655(s),
Brown solid (0.315 g, 75.4% yield). Mp.: 137e139 ꢁC 1H NMR
1562(s), 1518(s), 1305(s), 1233(s), 1089(s), 965(s), 890(m), 777(s).
(400 MHz, CDCl3)
2.70e2.75 (m, 1H), 4.18 (s, 5H), 4.41 (s, 2H), 4.49 (s, 2H), 5.01 (s, 2H),
6.07 (s, 1H), 6.59 (s, 1H). 13C NMR (400 MHz, CDCl3)
(ppm): 6.6,
22.7, 53.7, 68.5, 69.8, 70.0, 72.2, 104.3, 104.4, 145.0, 167.9. MS (ESI):
m/z 418 ([M þ H]þ). Anal. Calc for C19H18F3FeN3O: C, 50.41; H, 4.01;
O, 3.53%. Found: C, 50.31; H, 4.02; O, 3.54%. IR (KBr, cmꢂ1):
d (ppm): 0.44e0.48 (m, 2H), 0.77e0.85 (m, 2H),
2.2.17. N-(5-chloro-2-methylphenyl)-2-(5-ferrocenyl-3-
(trifluoromethyl)-1H-pyrazol-1-yl)acetamide (17)
d
Brown solid (0.375 g, 74.8% yield). Mp.: 154e156 ꢁC 1H NMR
(400 MHz, CDCl3) d (ppm): 2.11 (s, 3H), 4.22 (s, 5H), 4.47 (s, 2H), 4.60
(s, 2H), 5.23 (s, 2H), 6.66 (s, 1H), 7.05 (d, 1H, J ¼ 7.8 Hz), 7.09 (d, 1H,
n
¼ 3276(s), 3080(m), 1666(s), 1552(s), 1412(m), 1322(m), 1250(s),
J ¼ 7.8 Hz), 8.23 (s, 1H), 8.26 (s, 1H). 13C NMR (400 MHz, CDCl3)
1127(m), 969(s), 893(m), 808(s), 735(s).
d
(ppm): 16.8, 54.0, 68.7, 69.8, 70.2, 71.9, 104.8, 104.8, 120.9, 124.9,
125.4, 131.3, 132.3, 136.2, 145.7, 164.3. MS (ESI): m/z 503 ([M þ H]þ).
2.2.23. N-Cyclohexyl-2-(5-ferrocenyl-3-(trifluoromethyl)-1H-
pyrazol-1-yl)acetamide (23)
Anal. Calc for C23H19ClF3FeN3O: C, 55.06; H, 3.82; O, 3.19%. Found: C,
54.93; H, 3.83; O, 3.20%. IR (KBr, cmꢂ1):
n
¼ 3204(m), 1672(s),
Brown solid (0.334 g, 72.7% yield). Mp.: 139e141 ꢁC 1H NMR
1545(m), 1404(m), 1243(m), 1123(s), 976(m), 794(s).
(400 MHz, CDCl3)
d (ppm): 1.13e1.85 (m, 10H), 3.77e3.86 (m, 1H),

118
X.-F. Huang et al. / Journal of Organometallic Chemistry 706-707 (2012) 113e123
4.18 (s, 5H), 4.40 (s, 2H), 4.51 (s, 2H), 5.00 (s, 2H), 5.87 (s, 1H), 6.60
(s, 1H). 13C NMR (400 MHz, CDCl3)
(ppm): 24.3, 25.4, 32.5, 48.2,
52.9, 68.6, 69.3, 69.7, 73.6, 104.0, 104.1, 128.4, 128.9, 130.2, 140.4,
144.0, 165.3. MS (ESI): m/z 482 ([M þ H]þ). Anal. Calc for
C24H22F3FeN3O: C, 59.89; H, 4.61; O, 3.32%. Found: C, 60.04; H, 4.60;
d
53.9, 68.6, 69.8, 69.9, 72.3, 104.4, 104.4, 145.0, 165.6. MS (ESI): m/z
460 ([M þ H]þ). Anal. Calc for C22H24F3FeN3O: C, 57.53; H, 5.27; O,
O, 3.34%. IR (KBr, cmꢂ1):
n
¼ 2958(m), 1676(s), 1586(s), 1497(s),
3.48%. Found: C, 57.39; H, 5.29; O, 3.47%. IR (KBr, cmꢂ1):
2906(s), 1631(s), 1518(s), 1152(s), 1329(m), 1250(s), 1192(s), 1134(s),
1010(s), 976(s), 883(m), 804(s).
n
¼ 3410(s),
1398(s), 1326(m), 1257(s), 1195(s), 1141(s), 965(s), 873(m), 815(s),
765(s), 704(s).
2.2.29. 2-(5-Ferrocenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)-N,N-
dipropylacetamide (29)
2.2.24. N-(tert-butyl)-2-(5-ferrocenyl-3-(trifluoromethyl)-1H-
pyrazol-1-yl)acetamide (24)
Brown solid (0.306 g, 66.4% yield). Mp.: 63e64 ꢁC 1H NMR
Brown solid (0.285 g, 65.8% yield). Mp.: 132e134 ꢁC 1H NMR
(400 MHz, CDCl3)
d
(ppm): 0.90 (t, 3H, J ¼ 7.2 Hz), 0.94 (t, 3H,
(400 MHz, CDCl3)
d
(ppm): 1.31 (s, 9H), 4.19 (s, 5H), 4.42 (s, 2H), 4.52
J ¼ 7.2 Hz), 1.56e1.66 (m, 4H), 3.23 (t, 2H, J ¼ 8.0 Hz), 3.32 (t, 2H,
(s, 2H), 4.95 (s, 2H), 5.83 (s, 1H), 6.59 (s, 1H). 13C NMR (400 MHz,
J ¼ 7.6 Hz), 4.19 (s, 5H), 4.32 (s, 2H), 4.45 (s, 2H), 5.03 (s, 2H), 6.61 (s,
CDCl3)
d
(ppm): 28.5, 51.7, 54.4, 68.5, 69.8, 70.0, 72.3, 104.4, 104.4,
1H). 13C NMR (400 MHz, CDCl3)
d (ppm): 11.4, 20.8, 48.2, 51.9, 68.9,
145.1, 165.5. MS (ESI): m/z 434 ([M þ H]þ). Anal. Calc for
69.3, 69.6, 73.7, 104.2, 104.2, 144.3, 165.4. MS (ESI): m/z 462
C20H22F3FeN3O: C, 55.44; H, 5.12; O, 3.69%. Found: C, 55.63; H, 5.11;
([M þ H]þ). Anal. Calc for C22H26F3FeN3O: C, 57.28; H, 5.68; O, 3.47%.
O, 3.70%. IR (KBr, cmꢂ1):
n
¼ 3050(m), 1762(s), 1676(s), 1487(m),
Found: C, 57.12; H, 5.70; O, 3.46%. IR (KBr, cmꢂ1):
2978(s), 1662(s), 1466(s), 1398(m), 1223(s), 1147(s), 965(s), 883(m),
818(s), 743(m).
n
¼ 3442(m),
1439(s), 1360(s), 1237(s), 1134(s), 1086(s), 959(s), 901(m), 815(m),
783(s), 756(s).
2.2.25. N-Isobutyl-2-(5-ferrocenyl-3-(trifluoromethyl)-1H-pyrazol-
1-yl)acetamide (25)
2.2.30. N,N-dibutyl-2-(5-ferrocenyl-3-(trifluoromethyl)-1H-
pyrazol-1-yl)acetamide (30)
Brown solid (0.363 g, 83.7% yield). Mp.: 117e119 ꢁC 1H NMR
Brown solid (0.307 g, 62.7% yield). Mp.: 66e68 ꢁC 1H NMR
(400 MHz, CDCl3)
d
(ppm): 0.83 (d, 6H, J ¼ 6.4 Hz), 1.67e1.75 (m,
(400 MHz, CDCl3)
d
(ppm): 0.96 (t, 6H, J ¼ 7.2 Hz), 1.28e1.39 (m,
1H), 3.12 (d, 2H, J ¼ 5.6 Hz), 4.18 (s, 5H), 4.41 (s, 2H), 4.52 (s, 2H),
4H),1.54e1.62 (m, 4H), 3.27 (t, 2H, J ¼ 7.6 Hz), 3.37 (t, 2H, J ¼ 7.6 Hz),
5.05 (s, 2H), 6.09 (s, 1H), 6.61 (s, 1H). 13C NMR (400 MHz, CDCl3)
4.22 (s, 5H), 4.35 (s, 2H), 4.47 (s, 2H), 5.05 (s, 2H), 6.63 (s, 1H). 13C
d
(ppm): 19.8, 28.2, 46.7, 53.7, 68.6, 69.8, 70.0, 72.2, 104.4, 104.4,
NMR (400 MHz, CDCl3) d (ppm): 13.8, 20.2, 31.1, 47.3, 51.9, 68.9,
145.1, 166.5. MS (ESI): m/z 434 ([M þ H]þ). Anal. Calc for
69.3, 69.8, 73.7, 104.2, 104.2, 144.3, 165.5. MS (ESI): m/z 490
C20H22F3FeN3O: C, 55.44; H, 5.12; O, 3.69%. Found: C, 55.34; H, 5.14;
([M þ H]þ). Anal. Calc for C24H30F3FeN3O: C, 58.91; H, 6.18; O, 3.27%.
O, 3.68%. IR (KBr, cmꢂ1):
n
¼ 2896(s), 1676(s), 1508(s), 1452(s),
Found: C, 59.11; H, 6.16; O, 3.28%. IR (KBr, cmꢂ1):
2968(s), 1652(s), 1508(m), 1462(s), 1389(m), 1334(m), 1239(s),
1120(s), 953(s), 806(s), 741(m).
n
¼ 3462(m),
1384(m), 1237(s), 1203(s), 1111(s), 965(s), 856(m), 818(s), 739(s).
2.2.26. 2-(5-Ferrocenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)-N-
octylacetamide (26)
2.2.31. 2-(5-Ferrocenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)-1-
(piperidin-1-yl)ethanone (31)
Brown solid (0.360 g, 73.6% yield). Mp.: 61e63 ꢁC 1H NMR
(400 MHz, CDCl3)
10H), 1.45e1.48 (m, 2H), 3.28 (m, 2H), 4.20 (s, 5H), 4.43 (s, 2H), 4.53
d
(ppm): 0.88 (t, 3H, J ¼ 6.4 Hz), 1.25e1.29 (m,
Brown solid (0.283 g, 65.7% yield). Mp.: 132e134 ꢁC 1H NMR
(400 MHz, CDCl3) d (ppm): 0.84e0.90 (m, 1H), 1.53e1.61 (m, 2H),
1.89e1.92 (m, 2H), 3.28e3.37 (m, 2H), 3.73e3.75 (m,1H), 3.96e4.02
(s, 2H), 5.05 (s, 2H), 5.99 (s, 1H), 6.62 (s, 1H). 13C NMR (400 MHz,
CDCl3)
d
(ppm): 14.0, 22.6, 26.7, 29.1, 29.2, 31.7, 39.6, 53.8, 68.5, 69.8,
(m, 2H), 4.19 (s, 5H), 4.35 (s, 2H), 4.47 (s, 2H), 5.09 (s, 2H), 6.60 (s,
70.0, 72.2, 104.3, 104.3, 145.0, 166.4. MS (ESI): m/z 490 ([M þ H]þ).
1H). 13C NMR (400 MHz, CDCl3)
d (ppm): 23.3, 25.3, 45.1, 50.8, 67.8,
Anal. Calc for C24H30F3FeN3O: C, 58.91; H, 6.18; O, 3.27%. Found: C,
68.3, 68.8, 72.5, 103.2, 103.2, 143.4, 163.2. MS (ESI): m/z 446
([M þ H]þ). Anal. Calc for C21H22F3FeN3O: C, 56.65; H, 4.98; O,
3.59%. Found: C, 56.52; H, 4.97; O, 3.61%. IR (KBr, cmꢂ1):
59.09; H, 6.19; O, 3.26%. IR (KBr, cmꢂ1):
n
¼ 2988(s), 1681(s),
1569(m), 1456(s), 1393(s), 1239(s), 1187(s), 1115(s), 991(s), 879(m),
827(s), 723(m).
n
¼ 3482(m), 2936(s), 1648(s), 1511(m), 1456(s), 1340(m), 1237(s),
1134(s), 1007(s), 969(m), 811(s), 732(m).
2.2.27. N-Methyl-2-(5-ferrocenyl-3-(trifluoromethyl)-1H-pyrazol-
1-yl)-N-phenylacetamide (27)
2.2.32. 2-(5-Ferrocenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)-1-(2-
methylpiperidin-1-yl)ethanone (32)
Brown solid (0.407 g, 87.2% yield). Mp.: 95e97 ꢁC 1H NMR
(400 MHz, CDCl3)
d
(ppm): 3.35 (s, 3H), 4.15 (s, 5H), 4.38 (s, 2H),
Brown solid (0.293 g, 63.9% yield). Mp.: 124e125 ꢁC 1H NMR
4.44 (s, 2H), 4.82 (s, 2H), 5.32 (s, 1H), 6.58 (s, 1H), 7.31 (d, 2H,
(400 MHz, CDCl3) d (ppm): 0.83e0.87 (m, 2H),1.24e1.30 (m,
J ¼ 7.2 Hz), 7.40e7.44 (m, 1H), 7.47e7.51 (m, 2H). 13C NMR
1H),1.58e1.61 (m, 3H), 1.66e1.68 (m, 2H), 3.43e3.45 (m, 2H),
3.57e3.60 (m, 2H), 4.19 (s, 5H), 4.34 (s, 2H), 4.47 (s, 2H), 5.07 (s, 2H),
(400 MHz, CDCl3)
d (ppm): 37.7, 52.5, 68.7, 69.3, 69.8, 73.6, 104.1,
104.1, 127.4, 128.8, 130.3, 142.1, 144.1, 165.9. MS (ESI): m/z 468
6.60 (s, 1H). 13C NMR (400 MHz, CDCl3)
d (ppm): 16.9, 26.1, 30.6,
([M þ H]þ). Anal. Calc for C23H20F3FeN3O: C, 59.12; H, 4.31; O, 3.42%.
40.3, 48.1, 52.3, 53.4, 68.7, 69.4, 69.8, 73.6, 104.1, 104.1, 144.3, 164.2.
MS (ESI): m/z 460 ([M þ H]þ). Anal. Calc for C22H24F3FeN3O: C,
57.53; H, 5.27; O, 3.48%. Found: C, 57.41; H, 5.28; O, 3.50%. IR (KBr,
Found: C, 58.99; H, 4.30; O, 3.43%. IR (KBr, cmꢂ1):
1676(s), 1590(m), 1494(m), 1391(s), 1336(m), 1254(m), 1127(s),
959(s), 801(s), 701(s).
n
¼ 3410(m),
cmꢂ1):
n
¼ 3452(m), 2946(m), 1658(s), 1446(s), 1550(s), 1247(s),
1171(s), 993(s), 818(m), 732(m).
2.2.28. N-Ethyl-2-(5-ferrocenyl-3-(trifluoromethyl)-1H-pyrazol-1-
yl)-N-phenylacetamide (28)
2.2.33. 1-(3,5-Dimethylpiperidin-1-yl)-2-(5-ferrocenyl-3-
(trifluoromethyl)-1H-pyrazol-1-yl)ethanone (33)
Brown solid (0.411 g, 85.3% yield). Mp.: 113e115 ꢁC 1H NMR
(400 MHz, CDCl3)
J ¼ 7.2 Hz), 4.14 (s, 5H), 4.38 (s, 2H), 4.43 (s, 2H), 4.76 (s, 2H), 5.32 (s,
1H), 6.57 (s, 1H), 7.27 (d, 2H, J ¼ 7.2 Hz), 7.41e7.45 (m, 1H),
d
(ppm): 1.18 (t, 3H, J ¼ 7.2 Hz), 3.81 (q, 2H,
Brown solid (0.399 g, 84.2% yield). Mp.: 137e139 ꢁC 1H NMR
(400 MHz, CDCl3)
d
(ppm): 0.75e0.84 (m,1H), 0.91 (t, 6H, J ¼ 6.4 Hz),
1.26e1.33 (m, 1H), 1.58e1.66 (m, 2H), 1.84e1.87 (m, 1H), 2.08 (t, 1H,
J ¼ 8.0 Hz), 2.58 (t, 1H, J ¼ 8.4 Hz), 3.67e3.71 (m, 1H), 4.19 (s, 5H),
7.48e7.52 (m, 2H). 13C NMR (400 MHz, CDCl3)
d (ppm): 13.0, 44.7,

X.-F. Huang et al. / Journal of Organometallic Chemistry 706-707 (2012) 113e123
119
4.34 (s, 2H), 4.48 (s, 2H), 5.08 (s, 2H), 6.60 (s,1H).13C NMR (400 MHz,
n
¼ 3430(m), 3040(m),1765(m),1658(m),1442(m),1364(s),1257(s),
CDCl3)
d
(ppm): 19.0, 32.2, 42.1, 49.4, 52.2, 68.8, 69.4, 69.8, 73.7,
1144(s), 1082(s), 955(s), 777(s), 746(s).
104.1, 104.1, 144.4,163.9. MS (ESI): m/z 474 ([M þ H]þ). Anal. Calc for
C23H26F3FeN3O: C, 58.36; H, 5.54; O, 3.38%. Found: C, 58.55; H, 5.53;
O, 3.39%. IR (KBr, cmꢂ1):
n
¼ 3452(m), 2926(m), 1662(s), 1446(s),
2.3. Crystal structure determination
1250(s), 1137(s), 969(s), 828(m).
Single crystal X-ray diffraction measurements for compounds 19
and 30 were carried out on a Siemens Smart 1000 CCD diffrac-
tometer equipped with a graphite crystal monochromator situated
in the incident beam for data collection at room temperature. The
determination of unit cell parameters and data collections were
2.2.34. 2-(5-Ferrocenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)-1-(4-
methylpiperazin-1-yl)ethanone (34)
Brown solid (0.303 g, 65.8% yield). Mp.: 95e97 ꢁC 1H NMR
(400 MHz, CDCl3)
d
(ppm): 2.27 (s, 3H), 2.36e2.39 (t, 4H, J ¼ 6.0 Hz),
performed with MoeK
a
radiation (
l
¼ 0.71073 Å). Unit cell
3.48 (t, 2H, J ¼ 4.4 Hz), 3.61 (t, 2H, J ¼ 4.4 Hz), 4.12 (s, 5H), 4.28 (s,
2H), 4.42 (s, 2H), 5.00 (s, 2H), 6.53 (s, 1H). 13C NMR (400 MHz,
dimensions were obtained with least-squares refinements, and all
structures were solved by direct methods with SHELXL-97 [26]. All
the non-hydrogen atoms were located in successive difference
Fourier syntheses. The final refinement was performed by full-
matrix least-squares methods with anisotropic thermal parame-
ters for non-hydrogen atoms on F2. The hydrogen atoms were
added theoretically and riding on the concerned atoms. The crystal
data and structure refinement were listed in Table 3.
CDCl3)
d (ppm): 42.2, 45.1, 46.0, 51.6, 54.5, 54.8, 68.9, 69.4, 69.8,
73.6, 104.3, 104.3, 144.4, 164.5. MS (ESI): m/z 461 ([M þ H]þ). Anal.
Calc for C21H23F3FeN4O: C, 54.80; H, 5.04; O, 3.48%. Found: C, 54.97;
H, 5.05; O, 3.49%. IR (KBr, cmꢂ1):
n
¼ 3524(s), 2958(m), 2782(m),
1666(s), 1453(s), 1291(m), 1240(s), 1134(s), 979(m), 804(s).
2.2.35. 1-(4-Hydroxypiperidin-1-yl)-2-(5-ferrocenyl-3-
(trifluoromethyl)-1H-pyrazol-1-yl)ethanone (35)
Brown solid (0.256 g, 55.4% yield). Mp.: 193e195 ꢁC 1H NMR
2.4. Biological test
(400 MHz, CDCl3)
d (ppm): 0.79e3.57 (m, 9H), 4.19 (s, 5H), 4.33 (s,
2H), 4.46 (s, 2H), 5.03 (s, 2H), 6.60 (s, 1H). 13C NMR (400 MHz,
The antitumor activity of all the prepared compounds against
PC-3 and Bcap-37 cell lines were evaluated as described elsewhere
with some modifications [27]. Target tumor cell lines were grown
to log phase in RPMI 1640 medium supplemented with 10% fetal
bovine serum. After diluting to 2 ꢃ 104 cells mLꢂ1 with the
CDCl3)
d (ppm): 34.1, 42.2, 51.7, 66.3, 68.8, 69.5, 69.8, 73.5, 104.2,
104.2, 144.5, 164.3. MS (ESI): m/z 461 ([M þ H]þ). Anal. Calc for
C21H22F3FeN3O2: C, 54.68; H, 4.81; O, 6.94%. Found: C, 54.86; H,
4.80; O, 6.93%. IR (KBr, cmꢂ1):
n
¼ 3430(s), 1658(s), 1466(m),
1364(m), 1223(s), 1137(s), 979(s), 815(s).
complete medium, 100
mL of the obtained cell suspension was
added to each well of 96-well culture plates. The subsequent
incubation was permitted at 37 ꢁS, 5% CO2 atmosphere for 24 h
before the cytotoxicity assessments. Tested samples at pre-set
concentrations were added to 6 wells with adriamycin coassayed
as positive control. After 72 h exposure period, 100 mL of PBS con-
taining 0.5 mg/mL of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-
diphenyltetrazolium bromide) was added to each well. 4 h later,
2.2.36. 1-(4-Benzylpiperidin-1-yl)-2-(5-ferrocenyl-3-
(trifluoromethyl)-1H-pyrazol-1-yl)ethanone (36)
Brown solid (0.262 g, 48.9% yield). Mp.: 109e111 ꢁC 1H NMR
(400 MHz, CDCl3)
d (ppm): 0.82e3.08 (m, 9H), 3.78 (d, 1H,
J ¼ 13.6 Hz), 4.19 (s, 5H), 4.33 (s, 2H), 4.46 (s, 2H), 4.56 (d, 1H,
J ¼ 13.2 Hz), 5.05 (s, 2H), 6.60 (s, 1H), 7.14 (d, 2H, J ¼ 6.8 Hz),
7.20e7.23 (m, 1H), 7.28e7.32 (m, 2H). 13C NMR (400 MHz, CDCl3)
100
mL extraction solution (10% SDS-5% isobutyl alcohol-0.01 M
d
(ppm): 21.8, 22.4, 41.9, 51.7, 53.6, 68.6, 69.7, 69.8, 72.9,104.9,104.9,
HCl) was added. After an overnight incubation at 37 ꢁS, the optical
density was measured at a wavelength of 570 nm on an ELISA
microplate reader. In all experiments three replicate wells were
109.3, 120.3, 125.3, 128.9, 143.5, 165.9. MS (ESI): m/z 536 ([M þ H]þ).
Anal. Calc for C28H28F3FeN3O: C, 62.81; H, 5.27; O, 2.99%. Found: C,
63.00; H, 5.26; O, 3.00%. IR (KBr, cmꢂ1):
n
¼ 2936(s), 1631(s),
1442(s), 1216(s), 1203(m), 1110(s), 1024(m), 965(s), 791(s), 732(m).
Table 3
2.2.37. tert-Butyl-4-(2-(5-ferrocenyl-3-(trifluoromethyl)-1H-
pyrazol-1-yl)acetyl)piperazine-1-carboxylate (37)
Crystallographic data and structure refinements for compounds 19 and 30.
19
30
Brown solid (0.390 g, 71.3% yield). Mp.: 92e93 ꢁC 1H NMR
Formula
Mr
C22H17ClF6FeN3O
487.69
C24H30F3FeN3O
489.36
(400 MHz, CDCl3)
5H), 4.35 (s, 2H), 4.49 (s, 2H), 5.08 (s, 2H), 6.60 (s, 1H). 13C NMR
(400 MHz, CDCl3) (ppm): 28.4, 42.1, 45.1, 51.5, 68.9, 69.5, 69.8,
d (ppm): 1.45 (s, 9H), 3.44e3.62 (m, 8H), 4.19 (s,
Crystal system
Space group
Crystal size (mm3)
a (Å)
b (Å)
c (Å)
Triclinic
Pꢂ1
Monoclinic
P2(1)
d
0.24 ꢃ 0.23 ꢃ 0.18
9.4482(17)
14.457(3)
16.135(3)
82.827(2)
82.726(2)
75.941(2)
2110.6(6)
2
0.25 ꢃ 0.23 ꢃ 0.22
10.490(3)
10.176(3)
11.552(3)
90.00
94.342(3)
90.00
1229.6(6)
2
1.332
0.656
512
2.53e25.50
4543
73.5, 80.5, 104.3, 104.3, 144.6, 154.4, 164.6. MS (ESI): m/z 547
([M þ H]þ). Anal. Calc for C25H29F3FeN4O3: C, 54.96; H, 5.35; O,
8.79%. Found: C, 55.14; H, 5.34; O, 8.81%. IR (KBr, cmꢂ1):
a
b
g
(ꢁ)
(ꢁ)
(ꢁ)
n
¼ 3462(m), 2968(s), 1682(s), 1449(s), 1412(s), 1223(s), 1154(s),
973(m), 818(s).
Volume (Å3)
2.2.38. N,N-diisobutyl-2-(5-ferrocenyl-3-(trifluoromethyl)-1H-
pyrazol-1-yl)acetamide (38)
Z
Dc (g/cmꢂ3
)
1.535
0.886
992
2.37e26.00
8136
5323
617
0.835
Brown solid (0.329 g, 67.3% yield). Mp.: 117e119 ꢁC 1H NMR
m
(mmꢂ1
F (000)
rang (ꢁC)
)
(400 MHz, CDCl3)
d (ppm): 0.87 (s, 3H), 0.87 (s, 3H), 0.88 (s, 3H),
q
0.93 (s, 3H), 0.94 (s, 3H), 1.92e2.06 (m, 2H), 3.10 (d, 2H, J ¼ 7.6 Hz),
Reflections collected
Reflections unique
Parameters
3.22 (d, 2H, J ¼ 7.2 Hz), 4.20 (s, 5H), 4.31 (s, 2H), 4.45 (s, 2H), 5.02 (s,
3546
330
0.697
2H), 6.61 (s, 1H). 13C NMR (400 MHz, CDCl3)
d (ppm): 32.3, 42.9,
Goodness-of-fit on F2
45.5, 51.8, 68.9, 69.3, 69.8, 73.8, 104.2, 104.3, 139.7, 164.3. MS (ESI):
m/z 489.4 ([M þ H]þ). Anal. Calc for C20H21F3FeN4O: C, 58.91; H,
6.18; O, 3.27%. Found: C, 58.74; H, 6.20; O, 3.28%. IR (KBr, cmꢂ1):
R1,wR2 [I > 2
R1, wR2
s(I)]
0.0462, 0.1068
0.0818, 0.1188
0.0335, 0.0863
0.0488, 0.1004

120
X.-F. Huang et al. / Journal of Organometallic Chemistry 706-707 (2012) 113e123
Table 4
Table 5
ꢁ
ꢁ
Selected bond lengths (A) and angles ( ) for compounds 19 and 30.
Antitumor activity (IC50) against PC-3 and Bcap-37 cell lines of compounds 1e38.
C22H17ClF3FeN3O(19)
Bond lengths
C(17)eN(3)
C(16)eO(1)
N(2)eN(1)
H(31)eF(5)
H(6)eF(3)
H(3A)eO(2)
Comp. no
IC50 ꢀ SD(
mg/mL)
PC-3
Bcap-37
1.419(6)
1.216(5)
1.356(4)
2.682(5)
2.851(3)
2.102(3)
C(16)eN(3)
C(15)eN(2)
C(15)eC(16)
H(6)eF(2)
1.330(5)
1.446(5)
1.511(5)
2.784(3)
2.070(4)
1
2
3
4
5
6
7
8
20.33 ꢀ 1.61
13.07 ꢀ 3.25
8.36 ꢀ 1.43
35.25 ꢀ 3.72
36.25 ꢀ 3.22
17.34 ꢀ 2.47
27.34 ꢀ 2.36
32.05 ꢀ 3.35
34.09 ꢀ 1.97
29.09 ꢀ 2.41
20.34 ꢀ 2.44
25.23 ꢀ 3.34
15.01 ꢀ 1.80
34.25 ꢀ 3.52
31.27 ꢀ 2.23
34.42 ꢀ 3.82
38.23 ꢀ 2.87
34.75 ꢀ 3.01
35.53 ꢀ 2.63
31.15 ꢀ 4.25
37.72 ꢀ 4.18
34.03 ꢀ 1.93
36.49 ꢀ 2.68
31.15 ꢀ 2.32
38.39 ꢀ 3.94
34.46 ꢀ 2.85
18.34 ꢀ 3.30
34.49 ꢀ 3.63
19.31 ꢀ 2.21
34.36 ꢀ 2.41
35.69 ꢀ 2.96
34.65 ꢀ 3.48
37.47 ꢀ 4.68
36.49 ꢀ 4.20
36.06 ꢀ 4.12
39.16 ꢀ 3.18
38.16 ꢀ 2.92
31.49 ꢀ 2.76
30.42 ꢀ 4.05
33.15 ꢀ 4.09
32.15 ꢀ 4.01
45.73 ꢀ 4.92
19.43 ꢀ 1.22
4.35 ꢀ 0.87
16.21 ꢀ 2.48
15.35 ꢀ 3.23
18.15 ꢀ 3.24
19.34 ꢀ 3.16
12.28 ꢀ 2.13
16.47 ꢀ 1.42
6.53 ꢀ 1.23
H(6A)eO(1)
Bond angles
C(17)eN(3)eC(16)
N(3)eC(16)eC(15)
C(16)eC(15)eN(2)
C(15)eN(2)eC(11)
C(6)eH(6)/F(2)
N(6)eH(6A)/O(1)
122.6(3)
115.4(3)
111.5(3)
129.7(3)
128.2(3)
170.4(2)
N(3)eC(16)eO(1)
O(1)eC(16)eC(15)
C(15)eN(2)eN(1)
C(31)eH(31)/F(5)
C(6)eH(6)/F(3)
N(3)eH(3A)/O(2)
122.2(4)
122.3(3)
117.3(3)
135.5(3)
169.0(3)
177.7(3)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
Da
5-FUb
Cisplatinb
25.94 ꢀ 4.31
23.04 ꢀ 3.30
21.67 ꢀ 3.24
22.95 ꢀ 2.45
21.97 ꢀ 2.28
21.51 ꢀ 3.35
23.47 ꢀ 3.42
22.54 ꢀ 2.26
25.14 ꢀ 2.52
26.23 ꢀ 2.47
22.05 ꢀ 2.34
23.27 ꢀ 1.64
26.49 ꢀ 4.28
12.82 ꢀ 2.42
27.80 ꢀ 0.16
15.75 ꢀ 1.46
23.14 ꢀ 2.27
21.65 ꢀ 2.62
25.43 ꢀ 3.67
24.48 ꢀ 3.34
25.25 ꢀ 1.89
22.42 ꢀ 1.39
27.15 ꢀ 4.21
26.42 ꢀ 3.13
25.49 ꢀ 3.48
20.61 ꢀ 2.71
22.15 ꢀ 3.25
24.76 ꢀ 3.53
32.24 ꢀ 4.47
18.74 ꢀ 1.13
3.26 ꢀ 0.84
C24H30F3FeN3O(30)
Bond lengths
N(2)eN(3)
C(15)eC(16)
C(16)eN(1)
N(1)eC(21)
H(20C)eF(2)
Bond angles
N(3)eN(2)eC(15)
C(15)eC(16)eO(1)
C(15)eC(16)eN(1)
C(16)eN(1)eC(21)
C(18)eH(18B)/F(3)
1.356(8)
1.529(8)
1.352(8)
1.452(1)
2.822(1)
N(2)eC(15)
C(16)eO(1)
N(1)eC(17)
H(18B)eF(3)
1.432(8)
1.198(8)
1.471(1)
2.869(1)
118.2(5)
121.4(5)
115.0(5)
124.6(6)
123.1(6)
N(2)eC(15)eC(16)
O(1)eC(16)eN(1)
C(16)eN(1)eC(17)
C(21)eN(1)eC(17)
C(20)eH(20C)/F(2)
112.0(5)
123.6(6)
118.6(5)
116.7(6)
150.3(1)
used for each drug concentration. Each assay was carried out at
least three times. The results were summarized in Table 5.
3. Results and discussion
3.1. Structural results from single crystal X-ray diffraction
Single crystals of compounds 19 and 30 were obtained by the
slow evaporation of dichloromethane/methanol solutions. X-ray
crystal structure analysis of compounds 19 and 30 revealed the
structures depicted in Figs. 1 and 2, respectively. The selected bond
lengths (Å) and angles (ꢁ) were listed in Table 4.
Each data represents mean ꢀ S. D. from different experiments performed in
triplicate.
a
3-trifluoromethyl-5-ferrocenyl-pyrazol-1-yl-acetic acid.
Positive control for cytotoxicity.
b
ꢀ
Compound 19 crystallizes in the triclinic space group Pı with
two independent molecules in the asymmetric unit. There are
some differences between the two molecules. The principal
dimensions are carboxylate ester C]O (C16
¼
O1 1.216(5),
shortest FeeC(Cp) separation is 1.972(1) Å (Fe1eC10). The
three-atom link between the C5 rings also results in close to
C38 ¼ O2 1.220(5) Å) and NeC¼O with the values of 122.2(4) and
125.0(4)ꢁ. The average distances between the Fe center and each
carbon atom of its Cp rings in both molecules are 2.03e2.04 Å.
This distance is nearly identical to the analogs average distance
found in ferrocene. The shortest FeeC(Cp) separation is to C27,
with value of 2.022(4) Å. The three-atom link between the C5
rings results in close to eclipsed conformation for the C5 rings
eclipsed conformation for the C5 rings (
q
¼ 4.0ꢁ) and the
Cp0eFeeCp0 angle deviates somewhat from linearity (175.7ꢁ).
However, the pyrazole moiety was rotated out the plane of the Cp
ring (C4eC5eC6eC7eC8) by approximately 28.0ꢁ, which is a little
different from that of compound 19.
Layers of the two complexes are depicted in Fig. 3 and Fig. 4,
respectively. Because compound 19 crystallizes with two inde-
pendent molecules in the asymmetric unit, intermolecular HeF
bonds (H31eF5) between adjacent molecules lead to one kind of
1D chains and intermolecular HeF bonds (H6eF2 and H6eF3)
between adjacent molecules lead to another 1D chains. Then,
NeH/O interactions (N6eH6A/O1 and N3eH3A/O2) between
adjacent 1D chains generate a 2D layer, see Fig. 3.
(
q
¼ 0.5 and 1.1ꢁ) and the Cp0eFeeCp0 angles (Cp0 ¼ centroids of
Cp rings) both deviate somewhat from linearity (178.6 and
179.2ꢁ) [28,29]. In addition, the pyrazole moieties are rotated out
the plane of the Cp rings (C1eC2eC3eC4eC5 and
C23eC24e25eC26eC27) by approximately 45.7 and 43.4ꢁ,
respectively.
In the case of compound 30, it crystallizes in the monoclinic
space group P2(1) with one molecules in the asymmetric unit. The
principal dimensions are carboxylate ester C]O 1.198(8) Å,
NeC¼O 123.6(6)ꢁ and CeNeC 116.7(6)ꢁ. The average distance
between the Fe center and each carbon atom of its Cp rings is
also 2.04 Å. As is characteristic of other ferrocene compounds
the FeeCp0 separations range from 1.6467(6) to 1.6501(1) Å. The
In compound 30, intermolecular HeF bonds (H18BeF3)
between adjacent molecules lead to 1D chains. Then, CeH/F
interactions (C20eH20C/F2) between adjacent 1D chains
generate a 2D layer, see Fig. 4.
The bond lengths (Å) and angles (ꢁ) of the intermolecular
interaction were listed in Table 4.

X.-F. Huang et al. / Journal of Organometallic Chemistry 706-707 (2012) 113e123
121
Fig. 1. Molecular structure of compound 19 using Diamond (all hydrogen atoms are
omitted for clarity).
3.2. Biological activity
All the synthesized compounds were evaluated for their in vitro
antitumor activity against two human tumor cell lines: human
prostatic carcinoma cell line (PC-3) and human mammary carci-
noma cell line (Bcap-37) using the 3-(4,5-dimethylthiazol-2-yl)-
2,5-diphenyltetrazolium (MTT) method. 5-Fluorouracil (5-FU) and
cisplatin were employed as positive control. The results of the
in vitro cytotoxic effects of all the compounds were presented in
Table 5.
As shown in Table 5, compounds 1e38 exhibited fairly good
antitumor activity, which were much better than the starting
material (D). All the compounds were also exhibited better anti-
tumor activity against PC-3 cell line when compared to the results
against Bcap-37 cell line. Compounds 10, 3, 24, 8, 26 and 9
Fig. 3. (a) View of the layers of 19 along the a-axis. (b) View of the layers of 19 along
the b-axis. (c) View of the layers of 19 along the c-axis.
displayed relative good antitumor activity against PC-3 cell line.
Among them, compound 10 displayed the most potent antitumor
activity against PC-3 cell line with the IC50 value of 6.53
which was comparable to the positive control cisplatin.
mg/mL,
Subsequently SAR studies were performed to determine how
the substituents affected the antitumor activity. Compound 1
without any substituent on the phenyl ring showed moderate
antitumor activity with the mean IC50 value of 20.33
mg/mL when
Fig. 2. Molecular structure of compound 30 using Diamond (all hydrogen atoms are
omitted for clarity).
tested against PC-3 cell line. Introducing methoxy group(s) on the

122
X.-F. Huang et al. / Journal of Organometallic Chemistry 706-707 (2012) 113e123
Fig. 4. (a) View of the layers of 30 along the a-axis. (b) View of the layers of 30 along the b-axis. (c) View of the layers of 30 along the c-axis.
phenyl ring in 1 to form a class of compounds greatly increased the
antitumor activity against PC-3 cell line (e.g., 3, IC50 ¼ 8.36 g/mL;
g/mL). It can be seen that the
number and the position of the methoxy group may affect the
antitumor activity.
vitro. In particular, compound 10 was the most promising deriv-
m
ative, with the IC50 value of 6.53
cell line.
mg/mL when tested against PC-3
2, IC50 ¼ 13.07
m
g/mL; 8, IC50 ¼ 12.28
m
Acknowledgments
4. Conclusions
This work was supported by Key Program of Natural Science
Research by grants (CC20110016) from ChangZhou Science &
Technology Program of China and Condition Construction Cost of
Hefei University of Technology (407-037022).
In summary,
a
series of novel 2-(5-ferrocenyl-3-(tri-
fluoromethyl)-1H-pyrazol-1-yl)-N-amide derivatives (1e38) were
prepared and characterized. Among them, compounds 19 and
30 gave crystals suitable for X-ray structural analysis. All the
synthesized compounds were evaluated for their antitumor
activities. Some of the synthesized compounds exhibited
moderate to potent antitumor activities against PC-3 cell line in
Appendix A. Supplementary material
CCDC 842639 and 842640 contain the supplementary crystal-
lographic data for compounds 19 and 30. These data can be

X.-F. Huang et al. / Journal of Organometallic Chemistry 706-707 (2012) 113e123
123
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obtained free of charge from The Cambridge Crystallographic Data
Center via www.ccdc.cam.ac.uk/data_request/cif.
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