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R. Arancibia et al. / Journal of Organometallic Chemistry 696 (2011) 3238e3244
Mass spectrum (m/z): 324 [Mþ]. Anal.(%) Calc. for C15H12N2O3Fe: C,
55.56; H, 3.70 and N, 8.64; found: C, 55.60; H, 3.71 and N, 8.62.
(C6H4); 113.8 (C4H2O); 123.0 (C6H4); 140.0 (C6H4); 141.2
(C4H2Oipso); 147.3 (CH]N); 154.5 (C4H2Oipso); 193 (CO). Mass
spectrum (based on 187Re) m/z: 579 [Mþ]; 349 [Mþ ꢂ C11H8N3O3];
321 [Mþ ꢂ C11H8N3O3 ꢂ CO]; 293 [Mþ ꢂ C11H8N3O3 ꢂ 2CO]; 265
2.3.2. (5-Nitro-2-furfurylideneamino)cyrhetrene (1b)
Orange crystal, yield: 90% (58.7 mg, 0.13 mmol). IR (CH2Cl2,
[Mþ
ꢂ C11H8N3O3 ꢂ 3CO]. Anal. (%) Calc. for C20H14N3O6Re: C,
cmꢂ1): 2025 (s) (
d
n
CO); 1929 (vs) (
5.33 (t, 2H, J ¼ 2.3 Hz, C5H4); 5.65 (t, 2H, J ¼ 2.3 Hz, C5H4); 7.16 (d,
1H, J ¼ 3.8 Hz, C4H2O); 7.40 (d, 1H, J ¼ 3.8 Hz, C4H2O); 8.35 (s, 1H,
CH]N). 13C NMR:
78.6 (C5H4); 82.5 (C5H4); 112.8 (C4H2O); 114.6
n
CO); 1625 (w) (
n
C]N). 1H NMR:
41.45; H, 2.42 and N, 7.25; found: C, 40.98; H, 2.40 and N, 7.30.
2.3.7. N-[(5-Nitrofuran-2-yl)methylen]-benzene-1,4-diamine (4a)
d
Purple crystals, yield: 90% (208.0 mg, 0.9 mmol). IR (KBr): (
nC]
(C5H4ipso); 115.7 (C4H2O); 122.2 (C4H2Oipso); 149.0 (CH]N); 152.1
(C4H2Oipso); 193.2 (CO). Mass spectrum (based on 187Re) m/z: 474
[Mþ], 446 [Mþ ꢂ CO], 418 [Mþ ꢂ 2CO], 390 [Mþ ꢂ 3CO]. Anal. (%)
Calc. for C13H7N2O6Re: C, 32.91; H, 1.47 and N, 5.91; found: C, 32.69;
H, 1.41 and N, 5.82.
N cmꢂ1): 1628 (w). 1H NMR:
d
6.70 (d, J ¼ 8.2 Hz, 2H, C6H4); 7.11 (d,
J ¼ 3.8 Hz, 1H, C4H2O); 7.20 (d, J ¼ 8.2 Hz, 2H, C6H4); 7.41 (d,
J ¼ 3.8 Hz, 1H, C4H2O); 8.50 (s, 1H, CH]N). 13C NMR:
d: 112.6
(C4H2O); 114.1 (C4H2O); 123.5 (C6H4); 139.0 (C6H4); 147.3 (CH]N);
154.5 (C4H2Oipso). Mass spectrum m/z: 231 [Mþ]. Anal. (%) Calc. for
C11H9N3O3: C, 57.14; H, 3.90 and N, 18.18; found: C, 57.14; H, 3.89
and N, 18.20.
2.3.3. (5-Nitro-furfurylideneaminomethyl)ferrocene (2a)
The synthesis of complex 2a was carried out similarly to that
described for the general procedure, but by refluxing for 6 h using
a DeaneStark apparatus. Compound 2a was obtained as a red solid,
2.3.8. 4-Nitro-N-((5-nitrofuran-2-yl)methylene)benzenamine (4b)
Yellow crystals, yield: 90% (235.0 mg, 0.9 mmol). IR (KBr): (
nC]
yield: 90% (304.0 mg, 0.9 mmol). IR (KBr): (
1H NMR:
4.17 (s, 5H, C5H5); 4.18 (s, 4H, C5H4); 4.63 (d, J ¼ 1.5 Hz,
2H, CH2); 6.99 (d, J ¼ 3.8 Hz, 1H, C4H2O); 7.35 (d, J ¼ 3.8 Hz, 1H,
C4H2O); 8.07 (s, 1H, CH]N). 13C NMR:
60.0 (CH2); 68.4 (C5H4);
n
C]N cmꢂ1): 1628 (w).
N cmꢂ1): 1632 (w). 1H NMR:
d
7.28 (d, J ¼ 3.9 Hz, 1H, C4H2O); 7.34
d
(d, J ¼ 8.8 Hz, 2H, C6H4); 7.41 (d, J ¼ 3.9 Hz, 1H, C4H2O); 8.30 (d,
J ¼ 8.8 Hz, 2H, C6H4); 8.37 (s, 1H, CH]N). 13C NMR:
d 112.5 (C4H2O);
d
116.3 (C4H2O); 121.5 (C6H4); 125.2 (C6H4); 148.9 (CH]N); 152.1
(C4H2Oipso); 155.5 (C4H2Oipso). Mass spectrum m/z: 261 [Mþ]. Anal.
(%) Calc. for C11H7N3O5: C, 50.57; H, 2.68 and N, 16.09; found: C,
50.58; H, 2.69 and N, 16.02.
68.6 (C5H5); 68.7 (C5H4); 83.6 (C5H4ipso); 112.7 (C4H2O); 112.9
(C4H2O); 114.6 (C4H2Oipso); 148.2 (CH]N); 153.0 (C4H2Oipso). Mass
spectrum m/z: 338 [Mþ]. Anal. (%) Calc. for C16H14N2O3Fe: C, 56.80;
H, 4.14 and N, 8.28; found: C, 56.70; H, 4.10 and N, 8.32.
2.4. Biological assays
2.3.4. (5-Nitro-furfurylideneaminomethyl)cyrhetrene (2b)
A suspension of 3 ꢁ 106 epimastigotes of the Tulahuen strain of
T. cruzi was cultured at 28 ꢀC in monophasic Diamond’s culture
medium and was supplemented with 4 mM haemin and inactivated
bovine calf serum at a final concentration of 4%. Drugs dissolved in
DMSO (final concentration of 1%) were added to the culture media
to give 0.5e150 mM final concentrations. The parasite growth was
followed by nephelometry for 7e10 days. The nephelometry
readings were directly proportional to the concentration of para-
sites. No toxic effect of the DMSO alone was observed [24]. The
growth culture constant (k) for each drug concentration employed
was calculated using an exponential epimastigote growth curve
(regression coefficient > 0:97, P < 0:05). The slope resulting from
plotting the natural logarithm (Ln) of the nephelometry reading
versus time (hours) corresponds to k (hrꢂ1). The IC50 is defined as
the drug concentration needed to diminish k by 50%. It is calculated
by a linear regression analysis from the k values and the tested
concentrations. Reported values are the means of three indepen-
dent experiments.
The synthesis of complex 2b was carried out similarly to that
described for 2a. Complex 2b was obtained as brown solid, yield:
60% (78.0 mg, 0.16 mmol). IR (CH2Cl2, cmꢂ1): 2022 (s) (
n
CO); 1926
(s) (nCO); 1622 (w) (n d 4.60 (s, 2H, CH2); 5.32 (t, 2H,
C]N). 1H NMR:
J ¼ 2.3 Hz, C5H4); 5.45 (t, 2H, J ¼ 2.3 Hz, C5H4); 7.07 (d,1H, J ¼ 3.8 Hz,
C4H2O); 7.40 (d, 1H, J ¼ 3.8 Hz, C4H2O); 8.17 (s, 1H, CH]N). 13C
NMR:
d 41.4 (CH2); 83.5 (C5H4); 83.7 (C5H4); 112.8 (C4H2O); 114.6
(C5H4ipso); 115.7 (C4H2O); 122.2 (C4H2Oipso); 147.1 (CH]N); 152.1
(C4H2Oipso); 193.2 (CO). Mass spectrum (based on 187Re) m/z: 488
[Mþ]; 460 [Mþ ꢂ CO]; 432 [Mþ ꢂ 2CO]; 404 [Mþ ꢂ 3CO]. Anal. (%)
Calc. for C14H9N2O6Re: C, 34.43; H, 2.87 and N, 5.74; found: C, 34.60;
H, 2.91 and N, 5.80.
2.3.5. (N1-(Ferrocenylmethyl)-N2-(5-nitrofuran-2-yl)methylen)-
1,4-phenylendiamine (3a)
Complex 3a was isolated as red solid, yield: 90% (128.7 mg,
0.3 mmol). IR (KBr): (n d 4.00 (s, 2H,
C]N cmꢂ1): 1625 (w). 1H NMR:
CH2); 4.17 (t, J ¼ 2.4 Hz, 2H, C5H4); 4.20 (s, 5H, C5H5); 4.25 (t,
J ¼ 2.4 Hz, 2H, C5H4); 6.67 (d, J ¼ 8.2 Hz, 2H, C6H4); 7.11 (d, J ¼ 3.1 Hz,
1H, C4H2O); 7.31 (d, J ¼ 8.2 Hz, 2H, C6H4); 7.41 (d, J ¼ 3.1 Hz, 1H,
2.5. Crystal structure determination
C4H2O); 8.42 (s, 1H, CH]N). 13C NMR:
d 43.2 (CH2); 68.0 (C5H4);
68.1 (C5H5); 68.5 (C5H4); 85.6 (C5H4ipso); 112.6 (C4H2O); 112.8
(C4H2O); 113.0 (C4H2Oipso); 123.5 (C6H4); 139.0 (C6H4); 140.2
(C6H4); 148.7 (CH]N); 154.0 (C4H2O ipso). Mass spectrum m/z: 429
[Mþ], 200 [Mþ ꢂ C11H8N3O3]. Anal. (%) Calc. for C22H19N3O3Fe: C,
61.54; H, 4.43 and N, 9.79; found: C, 61.30; H, 4.20 and N, 9.72.
A summary of the fundamental crystal and refinement data for
1b are given in Table 2. Crystals of 1b were selected under a polar-
izing optical microscope and were glued on a glass fibre for a single-
Table 1
13C NMR shifts for Schiff bases.
Compound
13C NMRa (CH]N)
2.3.6. (N1-(Cyrhetrenylmethyl)-N2-(5-nitrofuran-2-yl)methylen)-
1,4-phenylendiamine (3b)
1a
1b
2a
2b
3a
3b
4a
4b
143.6
149.0
148.2
147.1
148.7
147.3
147.3
148.9
Complex 3b was isolated as red crystals, yield: 90% (114.4 mg,
0.2 mmol). IR (CH2Cl2, cmꢂ1): 2022 (s) (
nCO); 1924 (s) (nCO); 1630
(w) (
n
C]N). 1H NMR:
d
4.20 (s, 2H, CH2); 5.31 (t, J ¼ 2.1 Hz, 2H,
C5H4); 5.45 (t, J ¼ 2.1 Hz, 2H, C5H4); 6.69 (d, J ¼ 8.5 Hz, 2H, C6H4);
7.11 (d, J ¼ 3.8 Hz, 1H, C4H2O); 7.30 (d, J ¼ 8.5 Hz, 2H, C6H4); 7.41 (d,
J ¼ 3.8 Hz, 1H, C4H2O); 8.41 (s, 1H, CH]N). 13C NMR:
d: 41.2 (CH2);
a
83.6 (C5H4); 83.8 (C5H4); 107.7 (C5H4ipso); 112.9 (C4H2O); 113.3
ppm, CDCl3.