Ferrocene derivatives (II). Synthesis and reactions of 4-ferrocenyl-2-thiazolamine

Article abstract of DOI:10.1016/S0022-328X(01)00900-7

4-Ferrocenyl-2-thiazolamine (1) was prepared by the reaction of chloroacetylferrocene with thiourea. The thiazolimines 2-5 were synthesized by the condensations of the amine with aromatic aldehydes. The reaction of imine 2 with thioglycollic acid produced

Full text of DOI:10.1016/S0022-328X(01)00900-7

Journal of Organometallic Chemistry 637–639 (2001) 742–744
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Ferrocene derivatives (II). Synthesis and reactions of
4-ferrocenyl-2-thiazolamine
Huairang Ma *, Yihua Hou, Yinjuan Bai, Jun Lu, Bingqin Yang
Department of Chemistry, Northwest Uni6ersity, Xi’an, 710069, China
Received 20 December 2000; received in revised form 30 March 2001; accepted 30 March 2001
Abstract
4-Ferrocenyl-2-thiazolamine (1) was prepared by the reaction of chloroacetylferrocene with thiourea. The thiazolimines 2–5
were synthesized by the condensations of the amine with aromatic aldehydes. The reaction of imine 2 with thioglycollic acid
1
produced thiazolidone 6. All products were characterized by elemental analysis, IR and H-NMR spectra. © 2001 Elsevier Science
B.V. All rights reserved.
Keywords: Synthesis; 4-Ferrocenyl-2-thiazolamine; Thiazolimines; Thiazolidone
1. Introduction
and antibacterials [4,5]. The search for biologically
active ferrocene derivatives has attracted considerable
attention [6,7]. Recently, Zakaria and Chohan reported,
respectively, antimicrobial and antibacterial ferrocene
derivatives [8,9]. We synthesized and characterized a
series of ferrocene derivatives with strong biological
activity [10,11]. In order to continue our research pro-
ject, we prepared another type of ferrocene derivative
which contained both the thiazole ring and Schiff base
structures. For this purpose, 4-ferrocenyl-2-thiazo-
lamine (1) has been prepared. The amine easily con-
denses with aromatic aldehydes to give the following
imines 2–5. The imine 2 cyclizes with thioglycollic acid
to produce the thiazolidone 6.
The thiazole ring is very important in nature. It
occurs, for example, in thiamine, a coenzyme required
for the oxidative decarboxylation of a-keto acids. A
tetrahydrothiazole also appears in the skeleton of peni-
cillin which is one of the first and still most important
of the broad-spectrum antibiotics. Thiazolamines are
key intermediates for synthesizing many pharmaceuti-
cals [1]. Some thiazolidones are valuable medicines
[2,3]. It is obvious that compounds with the thiazole
ring have potential biological activity. We also know
that some Schiff bases are effective antitumor drugs
* Corresponding author. Fax: +86-29-830-3511.
E-mail address: lujunyue@hotmail.com (H. Ma).
0022-328X/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(01)00900-7

H. Ma et al. / Journal of Organometallic Chemistry 637–639 (2001) 742–744
743
2. Experimental
aluminum oxide column with a mixture of diethyl
ether–petroleum ether (volume ratio: 1:3) as eluent.
Imines 3 and 4 were recrystallized from EtOH and
imine 5 from a mixture of benzene and petroleum ether.
1H-NMR spectra were recorded on an AM-300 MHz
spectrometer with TMS as an internal standard. IR
spectra were obtained using KBr pellets on a Bruker
Equinox-55 instrument. Elemental analysis was per-
formed using a PE-2000 analyzer.
2.2.1. Complex 2
1H-NMR (CDCl3, l ppm): l=8.98 (s, 1H), 8.05–
6.98 (m, 6H), 4.81 (s, 2H), 4.31 (s, 2H), 4.10 (s, 5H). IR
2.1. Complex 1
w
(cm−1): 3100, 3050, 1600. Anal. Calc. for
The chloroacetyl ferrocene 0.97 g (3.7 mmol) pre-
pared according to the literature [12] and thiourea 0.40
g (5.3 mmol) were dissolved in 10 ml of warm EtOH.
The mixture was refluxed for 1.5 h and then poured
into 80 ml of ammonia spirit. The yellow crystals that
formed were filtered and dried. After recrystallization
from the solvent of a mixture of benzene and petroleum
ether, 1.01 g of amine 1 was obtained. 1H-NMR
(Me2CO-d6, l ppm): l=6.45 (s, 1H), 4.65 (s, 2H), 4.20
(s, 2H), 4.04 (s, 5H), 2.61 (s, 2H). IR w (cm−1): 3490,
3100, 1640. Anal. Calc. for C13H12FeN2S: C, 54.95; H,
4.26; N, 9.86. Found: C, 55.03; H, 4.49; N, 9.70%.
Yield 96%. M.p. 190–192 °C.
C20H16FeN2S: C, 64.53; H, 4.33; N, 7.53%. Found: C,
64.87; H, 4.47; N, 7.51%. Yield 30%. M.p. 105–106 °C.
2.2.2. Complex 3
1H-NMR (CDCl3, l ppm): l=12.31 (s, 1H), 9.22(s,
1H), 7.54–6.88 (m, 5H), 4.77 (s, 2H), 4.31 (s, 2H), 4.09
(s, 5H). IR w (cm−1): 3370, 3100, 1605. Anal. Calc. for
C20H16FeN2OS: C, 60.59; H, 3.87; N, 6.73%. Found: C,
59.92; H, 4.24; N, 6.95%. Yield 45%. M.p. 164–165 °C.
2.2.3. Complex 4
1H-NMR (CDCl3, l ppm): l=12.30 (s, 1H), 9.18 (s,
1H), 7.65–6.88 (m, 4H), 4.76 (s, 2H), 4.32 (s, 2H), 4.09
(s, 5H). IR w (cm−1): 3450, 3100, 1605. Anal. Calc. for
C20H15BrFeN2OS: C, 51.42; H, 3.23; N, 5.99%. Found:
C, 51.58; H, 3.50; N, 5.74%. Yield 33%. M.p. 159–
160 °C.
2.2. Complexes 2–5
The amine 1 0.57 g (2 mmol) and corresponding
aldehyde (2 mmol) were dissolved in 15 ml of benzene
(ethanol for imine 3). One drop of piperidine was added
to the mixture solution. The solution was heated and
refluxed in a 50 ml flask equipped with a Dean–Stark
trap condenser until no water appeared (ca. 1 h). After
the reaction solution was concentrated and allowed to
stand overnight at room temperature, the red solid that
formed was filtered out. Imine 2 was purified on an
2.2.4. Complex 5
1H-NMR (CDCl3, l ppm): l=13.11 (s, 1H), 9.23 (s,
1H), 7.50–7.09 (m, 3H), 4.77 (s, 2H), 4.34 (s, 2H), 4.10
(s, 5H). IR w (cm−1): 3450, 3100, 1595. Anal. Calc. for
C20H14Cl2FeN2OS: C, 52.54; H, 2.58; N, 6.13%. Found:
C, 52.76; H, 2.75; N, 5.92%. Yield 44%. M.p. 169–
171 °C.

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H. Ma et al. / Journal of Organometallic Chemistry 637–639 (2001) 742–744
2.3. Complex 6
tadienyl ring form an AA%BB% system, while the hydro-
gen atoms of the other Cp moiety appear as a sharp
singlet. In the IR spectra of imines 2–5, the strong
absorption bands in the 1595–1610 cm−1 region corre-
spond to the CꢀN stretching vibrations, but not absorp-
tions of the CꢀN in the thiazole ring, because they are
very weak.
The imine 2 (745 mg, 2 mmol), 313 mg (3 mmol) of
thioglycollic acid, and 15 ml of benzene were placed in
a flask equipped with a Dean–Stark trap condenser.
After the mixture solution was refluxed for 4 h, the
solvent was removed under reduced pressure. The
residue glue was ground together with a saturated
aqueous solution of sodium bicarbonate. The formed
powder was filtered and washed with water. This crude
product 6 was recrystallized from EtOH to obtain
Acknowledgements
1
orange crystals. H-NMR (DMSO-d6, l ppm): l=7.50
The authors are grateful for financial support of this
project from the Natural Science Foundation of
Shaanxi Province, People’s Republic of China.
(m, 5H), 7.14 (s, 1H), 6.79 (s, 1H), 4.60 (s, 2H), 4.32 (s,
2H), 4.23 (s, 1H), 4.09 (s, 1H), 3.71(s, 5H). IR w
(cm−1): 3100, 1695, 1560. Anal. Calc. for
C22H18FeN2OS2: C, 59.20; H, 4.06; N, 6.28%. Found:
C, 58.83; H, 4.34; N, 6.05%. Yield 60%. M.p. 185–
187 °C.
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Chloroacetyl ferrocene and ferrocenylthiazolamine
cannot be synthesized by any reagents having oxidizing
properties, because the ferrocenyl group is easily oxi-
dized. Chloroacetylferrocene was prepared by the reac-
tion of ferrocene with chloroacetyl chloride, with
aluminum chloride as catalyst. The yield was only 20%.
Several methods for the synthesis of 2-thiazolamine
have been reported [13–17]. We first prepared 4-ferro-
cenyl-2-thiazolamine with Hantzsch’s method [18]; the
yield was 96%. When the amine condensed with aro-
matic aldehydes, the yields of imines were lower than
those of unsubstituted 2-thiazolamine. The ferrocenyl
group has not only an electronic, but also a steric
effect. The imine 2 cyclized with thioglycollic acid
smoothly to give thiazolidone under the present syn-
thetic conditions. This is consistent with the reported
literature [19].
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1
All products were characterized by IR, H-NMR and
elemental analysis. The spectroscopic data of the pre-
pared complexes are found to be identical with ex-
pected structures. In the 1H-NMR spectra of all
products, the four protons of the substituted cyclopen-
[18] E.B. Knott, J. Chem. Soc. (1947) 1656.
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