Synthesis and enantiomeric resolution of ferrocenyl(alkyl)azoles

Article abstract of DOI:10.1016/j.jorganchem.2003.08.039

Ferrocenyl(alkyl)azoles were synthesized in high yields by interaction of α-ferrocenylcarbinoles with azoles in aqueous-organic in the presence of HBF₄ or by interaction of α-ferrocenylcarbinoles with N,N′-carbonyldiimidazole, N,N′-thionyldiimi

Full text of DOI:10.1016/j.jorganchem.2003.08.039

Journal of Organometallic Chemistry 688 (2003) 138ꢀ143
/
www.elsevier.com/locate/jorganchem
Synthesis and enantiomeric resolution of ferrocenyl(alkyl)azoles
Alexander A. Simenel *, Yulia V. Kuzmenko, Elena A. Morozova, Mikhail M. Ilyin,
Irina F. Gun’ko, Lubov’ V. Snegur
A.N. Nesmeyanov Institute of Organo-Element Compounds, Academy of Sciences of Russia, 28 Vavilov St., 119991 Moscow, Russia
Received 23 June 2003; accepted 13 August 2003
Abstract
Ferrocenyl(alkyl)azoles were synthesized in high yields by interaction of a-ferrocenylcarbinoles with azoles in aqueousꢀ
/organic in
the presence of HBF4 or by interaction of a-ferrocenylcarbinoles with N,N?-carbonyldiimidazole, N,N?-thionyldiimidazole, N,N?-
thionyldibenzimidazole in boiling dichloromethane. The resulting enantiomers of ferrocenyl(alkyl)azoles and some carbinoles were
separated using HPLC on silica bonded chiral stationary phases based on cyclodextrins and modified cellulose.
# 2003 Elsevier B.V. All rights reserved.
Keywords: Ferrocene derivatives; Enantiomeric resolution; HPLC; Ferrocenyl(alkyl)azoles; N,N?-Thionyldiimidazole
1. Introduction
procedure [4], in aqueousꢀ
presence of the equimolar amount of 45% aqueous
HBF4 (2aꢀg). Benzotriazole, pyrazole and its derivatives
/
organic (H2Oꢀ
/
CH2Cl2) in the
Biologically active ferrocene compounds are of con-
tinuous interest in various current researches [1]. It was
found that some of the ferrocenyl(alkyl)azoles obtained
in racemic form displayed high antitumor activity and
low toxicity [2]. Therefore ferrocenyl(alkyl)azoles are
perspective potential ferrocene containing drugs. Earlier
HPLC method was used for separation of enantiomers
of ferrocene compounds [3].
We report here the synthesis of a number of new
ferrocenyl(alkyl)azoles. The separation of synthesized
enantiomers was carried out by HPLC on a chiral
columns with silica gel bonded cyclodextrins, cyclic
antibiotics and modified cellulose.
/
were used as heterocycles (Scheme 1).
The reaction with strongly basic azoles is known to
lead to protonated heterocycles only (H2Azꢁ). Earlier
we reported the method for introducing ferrocenylalkyl
groups into the molecules of imidazole (HIm, pKaꢂ
/
7.00) based on the reaction of a-ferrocenylcarbinoles
with N,N?-carbonyldiimidazole (CDI) [5]. Some trends
of the reaction were found. A reasonable scheme is
suggested (Scheme 2).
The carbamate group ImOCOÃ at a-position to the
/
ferrocene fragment is a labile, good-leaving group open
for nucleophilic attack by imidazole eliminated in the
second stage. The similar derivatives of imidazole (5a, b)
were obtained from the reaction between CDI and v-
ferrocenyl alcohols (2-ferrocenylethanol, 4-ferrocenyl-
butanol). Structures of compounds 5a and 5b were
further supported by a strong IR-absorption (KBr) at
2. Results and discussion
2.1. Synthesis
1760ꢀ
/
1770 cmꢃ1 (CÄ
/O stretch vibration). This speaks
in favor of species 3 to actually serve as an intermediate
in the reaction. Moreover, (N-alcoxy-carbonyl)- and
(N-aryloxy-carbonyl)-imidazoles (carbamates) were
found to form under the same conditions [6] (Scheme 3).
If the approach to a hydroxyl group is sterically
Ferrocenyl(alkyl)azoles with nitrogen containing het-
erocycles (pKa of the conjugate free acids less than 6)
were synthesized according to known, well reproduced
hindered (Rꢂ
the lone product is the source carbinol 1. However, if in
/
t-Bu), the reaction does not proceed, and
* Corresponding author.
E-mail address: alexsim@ineos.ac.ru (A.A. Simenel).
0022-328X/03/$ - see front matter # 2003 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2003.08.039

A.A. Simenel et al. / Journal of Organometallic Chemistry 688 (2003) 138ꢀ
/
143
139
It is known that thionyl containing analogs of CDI
have similar reactivity [7]. We synthesized N,N?-thio-
nyldiimidazole (TDI) by the procedure described [8].
The thionyl containing derivatives obtained were used in
the reaction with ferrocenyl alcohols. The yields of
ferrocenylalkylated imidazoles are similar to those for
the reaction with CDI (Table 1, Scheme 5).
The results obtained moved us to prepare N,N?-
thionyldibenzimidazole (TDBI) from thionyl chloride
and benzimidazole in chloroform. Analogously, ferro-
cenylalkylated benzimidazoles were obtained in high
yields from the reaction between a-ferrocenylcarbinoles
and TDBI in boiling dichloromethane (Scheme 6, Table
2).
Scheme 1.
It is worthy of note that these simple procedures allow
us to realize the ferrocenylalkylation reactions of
imidazole and benzimidazole selectively. Actually 1N-
ferrocenyl(alkyl)imidazole or benzimidazole were the
single products formed.
2.2. Enantiomeric separation
Ferrocenyl(alkyl)azoles were prepared from racemic
carbinols and thus contain one chiral carbon center in
their structure and give racemic mixtures of two
enantiomers. In order to separate mixtures of enantio-
Scheme 2.
meric ferrocene derivatives, for example*ferroceny-
/
lethanol, Armstrong et al. [3] used HPLC on columns
with bonded b-cyclodextrin. In our work, we used
HPLC columns based on b- and g-cyclodextrins and
modified cellulose (Chiralcel OD and Chiralcel OD-H).
The enantiomeric separation data are summarized in
Table 3.
The use of the columns with bonded modified
cellulose gave better results in comparison with those
with bonded cyclodextrins. The size of the ferrocenyl
moiety present in the molecule obviously permits for-
mation of an inclusion complex with b-cyclodextrin
which offers a relatively hydrophobic conical cavity with
approximate diameter 7.8 A to the ‘guest’. The chiral
recognition of the ‘guest’ enantiomers results from
enantioselective steric or polar interactions of the
ferrocene substituent with hydroxyl groups sticking
out on the surface of the cone of the cyclodextrin
molecule. In our cases, such interaction cannot be
realized for all compounds. It is connected first with
rather bulk substituents at the a-carbon atom (Ph,
C5H4Mn(CO)3, BIm etc.), and secondly, in case of
Scheme 3.
source alcohol Rꢂ
/
Fc, C5H4Mn(CO)3, the interaction
with CDI results to ferrocenyl(alkyl)imidazoles (yields
81 and 83% accordingly). We ascribe these results to the
major mobility of a hydroxyl group located between two
elementoorganic substitutes. If the initial carbinol has
nucleophilic group (OH, NR2, etc.) the intramolecular
nucleophilic substitution takes place (Scheme 4). Thus,
the reaction between 1-ferrocenyl-1,4-butandiol 6 and
N,N?-carbonyldiimidazole leads to 2-ferrocenyltetrahy-
drofuran 7 as the single product.
compound 8h*ferrocenophane fragment simply cannot
/
be included in the cone of cyclodextrine. On the other
hand, recognition mechanism on cellulose is connected
apparently, with formation of specific hydrogen bonds
between the nitrogen atom of azole fragments or the
hydroxyl group of carbinols and carbamate units of the
modified cellulose. It was proved by the introduction of
electron accepting substituents (CF3, COOH 2b, 2c, 2f
Scheme 4.

140
A.A. Simenel et al. / Journal of Organometallic Chemistry 688 (2003) 138ꢀ143
/
Table 1
Yields of ferrocenyl(alkyl)imidazoles from the reactions of with CDI, TDI
Number
Number
R1
R2
Yield, % (CDI)
Yield, %(TDI)
1a
1b
1c
1d
1e
1f
8a
8b
8c
8d
8e
8f
H
H
Me
80
85
81
78
82
80
83
89
81
75
86
87
83
80
84
81
88
80
H
H
Et
n-Pr
H
H
Ph
Me
Me
H
1g
1h
1i
8g
8h
8i
C5H4Mn(CO)3
[3]-Ferrocenophanol-1
H
Fc
‘‘Kratos MS-890’’ spectrometer at 70 eV, and IR spectra
were recorded with a IR-20 spectrometer (Karl Zeiss).
Dichloromethane was dried over CaCl2, CDI was
purchased from Lancaster and used without purifica-
tion. TDI was prepared by interaction between thio-
nylchloride and imidazole. Carbinols 1bꢀf,g, 6 were
/
synthesized by acylation of ferrocene by corresponding
acid chlorides or acid anhydride [9] with the subsequent
reduction by lithium aluminium hydride in Et2O [10]. 2-
Ferrocenyl-2-hydroxypropane 1e was obtained by the
reaction of ferrocene with acetone in sulfuric acid [11].
Carbinols 4a,b were synthesized by reduction of corre-
sponding acids by lithium aluminium hydride in Et2O
[12].
Scheme 5.
Table 2
Yields of ferrocenyl(alkyl)benzimidazoles in the reaction with TDBI
Number
Number
R1
R2
Yield, %
1a
1b
1c
1d
1e
1f
9a
9b
9c
9d
9e
9f
H
H
85
82
85
87
75
76
H
Me
Et
H
H
n-Pr
Ph
3.1. Synthesis of ferrocenyl(alkyl)azoles
H
Me
Me
3.1.1. General procedure 1 [4]
To a mixture of 1.0 mmol of ferrocenylcarbinol and
1.0 mmol of the corresponding azoles in 1.0 ml of
methylene dichloride, 0.18 ml of 45% aqueous solution
of fluoroboric acid was added under vigorous stirring.
The agitation was continued for 5 min then 15 ml of
and 2g) in pyrazole. In ferrocenyl(ethyl)-1N-(3-carboxy-
5-methyl)pyrazole 2c, the formation of dimers due to an
intermolecular hydrogen bond is possible. In these cases,
the separation of enantiomers was not achieved both in
normal, and in reversed-phase modes on all columns
used. The difficulties in separation of enantiomers of
imidazole 8h may result from the impossibility recognize
two enantiomers of the ferrocenophane fragment.
Et2O, the same amount of cold water, and 5ꢀ10 mg of
/
ascorbic acid were added to the reaction flask. After
vigorous shaking of the mixture the organic solution
was separated, washed with cold water (5ꢄ15 ml), the
/
solvent was removed and the residue was dried over
CaCl2.
3. Experimental
3.1.2. Ferrocenyl(ethyl)pyrazole (2a)
Yield 86%. Orange crystals, m.p. 52ꢀ54 8C, Anal.: C,
64.38; H, 5.91; N, 9.79%. Calc. for C15H16FeN2: C,
64.31; H, 5.76; N, 10.00%. MS m/z (relative intensity,
/
1H-NMR spectra were obtained on a ‘‘Bruker-200-
WP’’ instrument. EI mass spectra were taken on a
Scheme 6.

A.A. Simenel et al. / Journal of Organometallic Chemistry 688 (2003) 138ꢀ
/
143
141
Table 3
Enantiomeric separation of racemic mixtures
3.1.3. Ferrocenyl(ethyl)-1N-(3-trifluoromethyl-5-(2)-
thiophene)pyrazole (2b)
Yield 84%. Yellowꢀorange oil, MS m/z (%): 430 (88)
/
[M]ꢁ. IR (KBr) n, cmꢃ1: 3115, 3005, 2950, 1520, 1423,
1345,1223, 1191, 1154, 998, 834, 726, 498. 1H-NMR
(DMSO-d6, d, ppm): 1.65 (d, 3H, CH3); 3.85ꢀ4.00 (m,
/
9H, Fc); 5.45 (q, 1H, CH); 6.87 (s, 1H, CH); 7.10 (s, 1H,
CH); 7.35 (s, 1H, CH), 7.63 (s, 1H, CH).
3.1.4. Ferrocenyl(ethyl)-1N-(3-carboxy-5-
methyl)pyrazole (2c)
Yield 62%. Yellowꢀ
(dec.), MS m/z (%): 338 (38) [M]ꢁ. IR (KBr) n, cmꢃ1
3160, 2931,1715ꢀ1680, 1421, 1265, 1132, 1063, 974, 853,
713, 665, 517, 498. H-NMR (DMSO-d6, d, ppm): 1.49
(d, 3H, CH3); 2.10 (s, 3H), 3.97ꢀ4.15 (m, 9H, Fc); 5.15
/
brawn crystals, m.p. 162ꢀ164 8C
/
:
/
1
/
(q, 1H, CH); 7.80 (s, 1H, CH); 7.10 (s, 1H, CH); 7.35 (s,
1H, CH), 10.85 (s, 1H, OH).
3.1.5. Ferrocenyl(ethyl)benzotriazole (2d)
Yield 97%. Orange crystals, m.p. 82 8C, Anal.: C,
64.38; H, 5.14; N, 12.54%. Calc. for C18H17FeN3: C,
65.28; H, 5.17; N, 12.69%. MS m/z (%): 331 (43) [M]ꢁ.
IR (KBr) n, cmꢃ1: 3125, 2943, 1640, 1567, 1490, 1402,
1
1220, 1100, 891, 470. H-NMR (CDCl3, d, ppm): 2.05
(d, 3H, CH3); 4.05ꢀ4.27 (m, 9H, Fc); 4.32 (q, 1H, CH);
/
6.00 (s, 1H, CH); 7.22 (s, 1H, CH); 7.49 (s, 1H, CH).
3.1.6. Ferrocenyl(ethyl)-1N-(3,5-dimethyl)pyrazole
(2e)
Yield 92%. Orange crystals, m.p. 74ꢀ76 8C, Anal.: C,
/
66.80; H, 6.56; N, 8.38%. Calc. for C17H20FeN2: C,
66.25; H, 6.54; N, 9.09%. MS m/z (%): 308 (97) [M]ꢁ.
IR (KBr) n, cmꢃ1: 3010, 2890, 1560, 1470, 1009, 840,
1
778, 539, 472. H-NMR (CDCl3, d, ppm): 1.24 (d, 3H,
CH3); 1.78 (s, 3H), 2.17 (s, 3H), 4.05ꢀ/4.25 (m, 9H, Fc);
5.25 (q, 1H, CH); 5.72 (s, 1H, CH).
3.1.7. Ferrocenyl(ethyl)-1N-(3-trifluoromethyl-5-
methyl)pyrazole (2f)
Yield 88%. Yellow crystals, m.p. 47 8C, MS m/z (%):
362 (91) [M]ꢁ. IR (KBr) n, cmꢃ1: 3029, 2898, 1564,
1456, 1265, 1011, 844, 776, 547, 472. 1H-NMR (DMSO-
d6, d, ppm): 1.52 (d, 3H, CH3); 2.43 (s, 3H), 4.01ꢀ4.08
/
(m, 9H, Fc); 5.34 (q, 1H, CH); 7.32 (s, 1H, CH).
3.1.8. Ferrocenyl(ethyl)-1N-(3,5-
ditrifluoromethyl)pyrazole (2g)
Yield 87%. Dark brown oil, MS m/z (%): 416 (100)
[M]ꢁ. IR (KBr) n, cmꢃ1: 3010, 2964, 1575, 1510, 1462,
1
1415, 1396, 1163, 1040, 987, 840, 715, 498. H-NMR
%): 280 (95) [M]ꢁ. IR (KBr) n, cmꢃ1: 3115, 2965, 1525,
1411, 1293, 1120, 1045, 968, 853, 720, 665, 538, 498. 1H-
NMR (DMSO-d6, d, ppm): 1.53 (d, 3H, CH3); 4.01ꢀ
/
4.15 (m, 9H, Fc); 5.19 (q, 1H, CH); 6.00 (s, 1H, CH);
7.22 (s, 1H, CH); 7.49 (s, 1H, CH).
(DMSO-d6, d, ppm): 1.63 (d, 3H, CH3); 4.01ꢀ
9H, Fc); 5.26 (q, 1H, CH); 7.27 (s, 1H, CH).
/4.10 (m,

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/
3.1.9. General procedure 2 [5]
3.1.15. Ferrocenyl(butyl)imidazole (8d)
Yield 78% (83%). Dark brown oil, MS m/z (%): 308
(100) [M]ꢁ. IR (KBr) n, cmꢃ1: 3109, 2972, 2885, 1692,
A mixture 1 mmole of ferrocenylcarbinol and 1.3
mmole CDI (or N,N?-thionyldiimidazole, N,N?-thionyl-
dibenzimidazole) in anhydrous CH2Cl2 was refluxed for
1 h. The resulting mass was cooled, 50 ml ether was
added and then washed by 20% solution of phosphoric
1511, 1425, 1292, 1174, 1118, 1090, 1040ꢀ
835, 754. 1H-NMR (CDCl3, d, ppm): 0.93 (m, 3H,
CH3); 1.15 (m, 2H, CH2); 2.00 (m, 2H, CH2); 4.05ꢀ4.15
/1020, 923,
/
acid (2ꢄ
/
50 ml). The aqueous phase was alkalized up to
50 ml). The
(m, 9H, Fc); 4.92 (t, 1H, CH); 6.89 (s, 1H, CH); 7.01 (s,
1H, CH); 7.52 (s, 1H, CH).
pH 5 and then extracted by CH2Cl2 (2ꢄ
/
organic layer was dried over anhydrous Na2SO4.
Solvents were removed in vacuo. The resulting product
was dried over CaCl2.
3.1.16. Ferrocenyl(benzyl)imidazole (8e)
Yield 82% (80%). Yellow crystals, m.p. 91ꢀ
m/z (%): 342 (75) [M]ꢁ. IR (KBr) n, cmꢃ1: 3111, 2944,
2872, 1518, 1472, 1140, 1123, 1015, 927, 840, 740ꢀ710.
1H-NMR (CDCl3, d, ppm): 4.10ꢀ
4.25 (m, 9H, Fc); 6.15
(s, 1H, CH); 6.82 (s, 1H, CH); 7.05 (s, 1H, CH); 7.14ꢀ
/
92 8C, MS
/
3.1.10. (2-Ferrocenylethyloxy)-(carbonyl)-1-imidazole
(5a)
/
/
Yield 98%. Orange crystals, m.p. 94ꢀ96 8C, MS m/z
/
(%): 324 (80) [M]ꢁ. IR (KBr) n, cmꢃ1: 3245, 3090, 1764,
1487, 1430, 1383, 1335, 1261, 1192, 1117, 1019, 980, 850,
7.30 (m, 5H, Ph); 7.45 (s, 1H, CH).
1
824, 778, 487. H-NMR (DMSO-d6, d, ppm): 1.87 (t,
3.1.17. Ferrocenyl(iso-propyl)imidazole (8f)
Yield 80% (84%). Yellow crystals, m.p. 104ꢀ105 8C,
/
2H, CH2), 2.60 (t, 2H, CH2), 3.94ꢀ4.05 (m, 9H, Fc);
6.93 (s, 1H, CH); 7.40 (s, 1H, CH); 8.10 (s, 1H, CH).
/
MS m/z (%): 294 (23) [M]ꢁ. IR (KBr) n, cmꢃ1: 3118,
3090, 3011, 1510, 1482, 1398, 1380, 1281, 1215, 1116,
1
815, 724, 510, 482. H-NMR
1087, 1010, 910, 850, 830ꢀ
/
3.1.11. (4-Ferrocenylbutyloxy)-(carbonyl)-1-imidazole
(5b)
(CDCl3, d, ppm): 1.45 (s, 6H, CH3), 4.10ꢀ/4.19 (m, 9H,
Fc); 6.89 (s, 1H, CH); 6.93 (s, 1H, CH); 7.38 (s, 1H,
CH).
Yield 97%. Orange crystals, m.p. 74ꢀ75 8C, MS m/z
/
(%): 352 (100) [M]ꢁ. IR (KBr) n, cmꢃ1: 3250, 3065,
1762, 1486, 1419, 1397, 1336, 1281, 1192, 1109, 1022,
3.1.18. N-Imidazolyl-ferrocenyl-
cyclopentadienylmanganesetricarbonyl-methane (8g)
1
851, 824, 773, 489. H-NMR (DMSO-d6, d, ppm): 1.40
(m, 2H, CH2), 1.57 (m, 2H, CH2), 2.24 (m, 2H, CH2),
Yield 83% (81%). Dark red crystals, m.p. 98ꢀ100 8C,
/
3.92ꢀ4.01 (m, 9H, Fc); 4.23 (t, 2H CH2); 6.88 (s, 1H,
/
MS m/z (%): 468 (19) [M]ꢁ. IR (KBr) n, cmꢃ1: 3109,
3011, 2031, 1943 1513, 1381, 1215, 1115, 1083, 1011,
CH); 7.41 (s, 1H, CH); 8.08 (s, 1H, CH).
910, 850, 724, 482. 1H-NMR (DMSO-d6, d, ppm): 4.10ꢀ
/
3.1.12. Ferrocenyl(methyl)imidazole (8a)
Yield 80% (CDI) (75% (TDI)). Yellow crystals, m.p.
4.19 (m, 9H, Fc); 4.88 (s, 1H, CH); 5.18ꢀ5.24 (m, 4H)
/
7.59 (s, 1H, CH); 7.93 (s, 1H, CH); 8.38 (s, 1H, CH).
65 8C, MS m/z (%): 266 (100) [M]ꢁ. IR (KBr) n, cmꢃ1
:
1000,
4.12 (m, 9H,
3150ꢀ
/
2970, 1690ꢀ
/
1520, 1450, 1220ꢀ
/
1100, 1110ꢀ
/
3.1.19. [3]-Ferrocenophan-1-N-imidazole (8h)
830, 491. 1H-NMR (CDCl3, d, ppm): 4.15ꢀ
/
Yield 89% (88%). Yellow crystals, m.p. 151 8C, MS
m/z (%): 292 (60) [M]ꢁ. IR (KBr) n, cmꢃ1: 3118, 3090,
3011, 1510, 1482, 1398, 1380, 1281, 1215, 1116, 1087,
Fc); 4.83 (s, 2H, CH2); 6.87 (s, 1H, CH); 6.98 (s, 1H,
CH); 7.44 (s, 1H, CH).
1010, 910, 850, 830ꢀ
(DMSO-d6, d, ppm): 1.96 (m, 2H, CH2), 4.05ꢀ
/
815, 724, 510, 482. 1H-NMR
4.19
3.1.13. Ferrocenyl(ethyl)imidazole (8b)
/
Yield 85% (86%). Redꢀ
76 8C, MS m/z (%): 280 (38) [M]ꢁ. IR (KBr) n, cmꢃ1
3118, 2992, 2940, 2868, 1671, 1510, 1415ꢀ1390, 1240,
1115, 1090, 1010, 923, 840, 754, 641. H-NMR (CDCl3,
d, ppm): 1.73ꢀ1.77 (d, 3H, CH3); 4.10ꢀ4.16 (m, 9H,
Fc); 5.07ꢀ5.17 (q, 1H, CH); 6.86 (s, 1H, CH); 6.96 (s,
/
orange crystals, m.p. 75ꢀ
/
(m, 8H, 2Cp); 4.45 (t, 2H, CH2); 4.63 (t, 1H, CH); 6.64
(s, 1H, CH); 7.08 (s, 1H, CH); 7.51 (s, 1H, CH).
:
/
1
3.1.20. Diferrocenylimidazolylmethane (8i)
/
/
Yield 81% (80%). Yellowꢀbrown oil, MS m/z (%):
/
450 (25) [M]ꢁ. IR (KBr) n, cmꢃ1: 3107, 2885, 1693,
1509, 1464, 1412, 1281, 1226, 1110, 1088, 1051, 1009,
/
1H, CH); 7.44 (s, 1H, CH).
824, 759, 483. 1H-NMR (DMSO-d6, d, ppm): 3.95ꢀ
4.13
(m, 9H, Fc); 5.88 (s, 1H, CH); 6.89 (s, 1H, CH); 6.93 (s,
1H, CH); 7.38 (s, 1H, CH).
/
3.1.14. Ferrocenyl(propyl)imidazole (8c)
Yield 81% (87%). Yellow oil, MS m/z (%): 294 (65)
[M]ꢁ. IR (KBr) n, cmꢃ1: 3204, 3011, 2972, 1650, 1522,
1426, 1113, 1028, 844, 452. 1H-NMR (DMSO-d6, d,
3.1.21. Ferrocenyl(methyl)benzimidazole (9a)
ppm): 0.55 (t, 3H, CH3) 1.92 (m, 2H, CH2); 3.90ꢀ
(m, 9H, Fc); 4.73 (t, 1H, CH); 6.69 (s, 1H, CH); 7.02 (s,
1H, CH); 7.56 (s, 1H, CH).
/
4.11
Yield 85%. Yellow crystals, m.p. 123ꢀ
/
125 8C, MS m/z
2970,
(%): 316 (93) [M]ꢁ. IR (KBr) n, cmꢃ1: 3150ꢀ
/
1
1690ꢀ
/
1520, 1450, 1220ꢀ
/
1100, 1110ꢀ1000, 830, 491. H-
/

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/
143
143
NMR (CDCl3, d, ppm): 4.02ꢀ
2H, CH2); 6.96ꢀ7.12 (m, 2H); 7.45ꢀ
1H, CH).
/
4.20 (m, 9H, Fc); 5.01 (s,
was operated at a flow rate of 1.0 mlꢃ1 and ambient
temperature.
/
/7.52 (m, 2H) 8.10 (s,
Acknowledgements
3.1.22. Ferrocenyl(ethyl)benzimidazole (9b)
Yield 82%. Yellow crystals, m.p. 91ꢀ93 8C, MS m/z
/
(%): 330 (87) [M]ꢁ. IR (KBr) n, cmꢃ1: 3110, 2952, 1621,
We thank Maya Karadzhaeva for performing some
experiments. This work has been partially supported by
The Scientific Training Center of Biomedical Chemistry
(Grant No A0078, the Federal Target Program ‘‘Inte-
gration’’).
1
1490, 1290, 1113, 1010, 925, 843, 759, 490. H-NMR
(DMSO-d6, d, ppm): 1.72 (d, 3H, CH3); 4.00ꢀ4.25 (m,
/
9H, Fc); 5.57 (q, 1H, CH); 7.00 (m, 2H); 7.40 (m, 2H);
8.05 (s, 1H, CH).
3.1.23. Ferrocenyl(propyl)benzimidazole (9c)
Yield 85%. Yellow oil, MS m/z (%): 344 (45) [M]ꢁ.
IR (KBr) n, cmꢃ1: 3113, 2965, 1710, 1622, 1490, 1409,
1291, 1230, 1109, 836, 485. 1H-NMR (DMSO-d6, d,
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3.1.24. Ferrocenyl(butyl)benzimidazole (9d)
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/
1H, CH); 6.89 (s, 1H, CH); 7.01 (s, 1H, CH); 7.52 (s, 1H,
CH).
3.1.25. Ferrocenyl(benzyl)benzimidazole (9e)
Yield 75%. Dark brown oil, MS m/z (%): 392 (36)
[M]ꢁ. IR (KBr) n, cmꢃ1: 3111, 2952, 1624, 1493, 1410,
1
1293, 1231, 1110, 1009, 924, 852, 761, 498. H-NMR
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(DMSO-d6, d, ppm): 3.88ꢀ
CH); 7.01 (m, 2H, CH); 7.10ꢀ
2H, CH); 8.08 (s, 1H, CH).
/
4.18 (m, 9H, Fc); 6.65 (s, 1H,
/
7.25 (m, 5H, Ph); 7.42 (m,
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3.1.26. Ferrocenyl(iso-propyl)benzimidazole (9f)
Yield 76%. Yellow crystals, m.p. 140ꢀ143 8C, MS m/z
/
[5] A.A. Simenel, E.A. Morozova, Yu.V. Kuzmenko, L.V. Snegur, J.
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1
1495, 1400, 1291, 1230, 1110, 1020, 840, 760, 489. H-
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NMR (DMSO-d6, d, ppm): 2.14 (s, 6H, CH3), 4.18ꢀ4.31
(m, 9H, Fc); 7.39 (s, 1H, CH); 7.52 (m, 2H, CH); 7.71
(m, 2H, CH).
/
3.2. Chromatographic separation of enantiomers
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Following chiral columns (250ꢄ4.6 mm, 5 mm) were
/
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used: Chiracel OD, Chiracel OD-H, (R, R) Whelk-01
(Pirkle covalent), Chirobiotic T, Cyclobond I 2000. The
HPLC system, Bruker LC 31 with a UV 254 detector