Synthesis of new ferrocene derivatives with rod-like structure

Article abstract of DOI:10.1016/j.mencom.2015.03.010

The Suzuki-Miyaura cross-coupling of tris(4-ferrocenylphenyl)- and tris[4-(2-ferrocenylethynyl)phenyl]boroxines with functionalized iodoarenes gives new ferrocene derivatives of rod-like structure.

Full text of DOI:10.1016/j.mencom.2015.03.010

Mendeleev
Communications
Mendeleev Commun., 2015, 25, 111–113
Synthesis of new ferrocene derivatives with rod-like structure
Vladimir N. Okulov,* Damir A. Popov, Anastasia V. Panfilova,
Marina A. Dyadchenko, Dmitrii A. Lemenovskii and Victor P. Dyadchenko
Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russian Federation.
Fax: +7 495 932 8846; e-mail: okulov@org.chem.msu.ru
DOI: 10.1016/j.mencom.2015.03.010
The Suzuki–Miyaura cross-coupling of tris(4-ferrocenylphenyl)- and tris[4-(2-ferrocenylethynyl)phenyl]boroxines with functionalized
iodoarenes gives new ferrocene derivatives of rod-like structure.
Previously,1 we reported on the preparation of a series of rod-like
Br
Fe
COOH
compounds containing a biphenyl or terphenyl moiety bound to
ferrocenyl, which revealed liquid crystalline properties. Bulky and
easily polarizable ferrocene substituent often drastically changes
the mesomorphic behavior of liquid crystals. The advantage of
ferrocene is the stability of its oxidized and reduced forms and
a low red-ox potential. Thus, ferrocene is an ideal redox sensor
and permits to develop a homogeneous competitive assay. Among
known tracers,2–4 the ferrocenyl group is drawn close to the site
of contact between tracer and antibody and this proximity can
affect the red-ox transitions of ferrocenyl group up to the complete
deactivation.3 Consequently, it is important to design new markers,
with a ferrocenyl group being withdrawn from the ‘anchor’.
i, ii, iii
Fe
Fe
5
6 (94%)
NHR
HN
iv,v
O
7 R = Boc (86%)
8 R = H (90%)
vi, vii
Scheme 2 Reagents and conditions: i, BuLi, THF, –60°C; ii, CO2; iii, HCl,
H2O; iv, (COCl)2; v, BocNH(CH2)4NH2, Et3N, –18°C; vi, CF3COOH, CH2Cl2;
vii, KOH, H2O.
R
benzene ring bound directly to ferrocenyl and flexible spacer
were prepared as shown in Schemes 1 and 2, starting from the
accessible 4-ferrocenylaniline 1 and 4-bromophenylferrocene 5.
In these cases, usual methods of peptide synthesis were used
providing excellent yields.
Elongation of the rod-like fragment in the target compounds
was achieved by introduction of additional phenylene and acetylene
moieties on using the Suzuki–Miyaura cross-coupling. One of
the reactants, tris(4-ferrocenylphenyl)boroxine 9 (Scheme 3),
was prepared previously.5 Introduction of a triple carbon–carbon
bond in the molecule was achieved by the use of a new boroxine
11 (Scheme 3) which was synthesized† from bromo derivative 10
available by direct alkynylation of ferrocene.6
n
m
Fe
A
n = 0, 1; m = 1–3
R = OH, NH2, (CH2)3COOH, NHC(O)CH2CH2COOH,
C(O)NH(CH2)4NH2, NHC(O)CH2CH2NH2
Here we report on the syntheses of new ferrocene derivatives
A which possess a rod-like structure and contain ‘anchoring’
amino or carboxyl groups. The target compounds with one
O
O
O
NH2
Fe
i
Fe
1
B
NH
O
COOH
Fe
Br
O
3
9
2 (93%)
B
O
O
i–iv
BuiO
Fe
Fe
O
HO
NHBoc
O
NHBoc
3
11 (67%)
10
O
O
Scheme 3 Reagents and conditions: i, BuLi, –60°C; ii, (BuO)3B, –60°C;
iii, HCl, H2O; iv, azeotropic dehydration with xylene.
NH
NHR
1
Fe
†
Tris[4-(ferrocenylethynyl)phenyl]boroxine 11. A solution of 2.01 m
n-butyllithium (2 ml, 4.02 mmol) was added to a solution of 1-(4-bromo-
phenyl)-2-ferrocenylacetylene 10 (1.27 g, 3.48 mmol) at –60°C in argon
purge. The deep brick colored reaction mixture was stirred at –55 to
–60°C for 1 h resulting in an orange suspension of 4-ferrocenylethynyl-
phenyllithium. Tri-n-butyl borate (1.31 ml, 4.77 mmol) was added at
3 R = Boc (84%)
4 R = H (92%)
ii, iii
Scheme 1 Reagents and conditions: i, BuiOC(O)Cl, Et3N; ii, CF3COOH,
CH2Cl2; iii, KOH, H2O.
© 2015 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
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Mendeleev Commun., 2015, 25, 111–113
Iodoarenes 14 and 15 were synthesized by iodination of the
R1
corresponding arenes 12 and 13 according to a modified published
i
procedure7,8 (Scheme 4).
R1
Fe
2
9
+
I
54–80%
HIO4–I2
22 R1 = OH
COOH
65 °C
AcOH–H2SO4
23 R1 = (CH2)3COOH
k
24 R1 = NHC(O)CH2CH2COOH
25 R1 = NHC(O)CH2CH2NH2
12 k = 0
13 k = 1
I
COOH
k
R2
i
14 k = 0 (55%)
15 k = 1 (78%)
I
+
R2
Fe
11
2
48–69%
Scheme 4
26 R2 = NO2
27 R2 = NH2
28 R2 = (CH2)3COOH
Common methods of organic synthesis were used in prepara-
tion of iodo precursors 18–21 (Scheme 5).
Scheme 6 Reagents and conditions: i, 5 mol% Pd(PPh3)4, K2CO3, DMF,
H2O, 60°C.
O
O
i, ii
HO
NHBoc
I
NH
NHR
NH2
i
z
24
O2N
NH2
Fe
2
16 R = Boc, z = 1 (72%)
18 R = H, z = 1 (91%)
2
(94%)
iii, iv
iii, iv
29
30
17 R = Boc, z = 2 (70%)
19 R = H, z = 2 (75%)
O
O
O
O
O
O
NH
ii, iii
iv, v
, v
25
2
NHBoc
Fe
HO
I
NH2
I
NH
COOH
(92%)
q
NHBoc
q
31 (84%)
20 q = 1
21 q = 2 (88%)
Scheme 7 Reagents and conditions: i, succinic anhydride, CH2Cl2; ii,
BuiOC(O)Cl, Et3N, –18°C; iii, 30; iv, CF3COOH, CH2Cl2; v, KOH.
Scheme 5 Reagents and conditions: i, BuiOC(O)Cl, Et3N, –18°C; ii,
I(C6H4)zNH2 (z = 1, 2), –18°C; iii, CF3COOH, CH2Cl2; iv, KOH; v, CH2Cl2,
reflux.
To conclude, detailed procedures were developed for the
preparation of a range of ferrocenyl compounds with a rod-like
structure. The compounds obtained can find applications as pre-
cursors for new calamitic liquid crystals, and the anchor groups
permit their further modification, such as elongation of molecule,
and as electrochemical markers, for example, in immunoanalysis.
Starting from boroxines 9, 11 and different iodoarenes, markers
containing biphenyl moiety were synthesized by palladium-
catalyzed cross-coupling (Scheme 6).‡ Note that attempted pre-
paration of similar terphenyl derivatives from boroxines 9 and 11
and iodobiphenyls 15, 19, 21 was unsuccessful.§
This work was supported by the Russian Foundation for Basic
Research (grant no. 12-03-00836-a) andinpartbyM. V. Lomonosov
Moscow State University Program of Development.
Thus obtained 4'-ferrocenyl[1,1']biphenyl-4-amine 30 was
converted into compounds 24 and 25 (Scheme 7).
Online Supplementary Materials
Supplementary data associated with this article (synthetic
procedures and characteristics of compounds 2–4, 6–8, 12,
–60 °C to the suspension within 2 min. The precipitate of lithium derivative
dissolved and the reaction mixture became brown. The mixture was allowed
to warm gradually to –10°C in 1 h, then to ambient temperature and
stirring was continued for 1 h. Water (2 ml) was added followed by a
solution of hydrochloric acid (0.7 ml) in water (8.5 ml). Organic layer
was separated, diluted with benzene, washed with water, dried over sodium
sulfate and evaporated under reduced pressure. Mixture of xylenes (25 ml)
was added to the residue and the solvent was evaporated again under
reduced pressure at bath temperature 93°C. Dry residue was washed with
hot light petroleum and dried in air to give boroxine 11 (0.74 g, 68%)
as an orange powder, decomp. over 205°C. 1H NMR (CDCl3) d: 4.24 and
4.27 (m and s, 2H + 5H, C5H4, C5H5), 4.55 (m, 2H, C5H4), 7.60–7.62
a mixture of dichloromethane (25 ml) and water (25 ml) and acidified
to pH 3 with conc. HCl. Organic layer was separated, water layer was
extracted with dichloromethane (3×20 ml). Combined organic extracts
were thoroughly washed with water to remove DMF, dried over Na2SO4
and evaporated to dryness. The residue was subjected to column chro-
matography on silica gel. Using benzene two yellow bands were eluted
and discarded. Subsequent elution with benzene–ethyl acetate (1:1)
afforded acid 28 (0.115 g, 47%), mp 211–212°C. 1H NMR (DMSO-d6)
d: 4.25 (m, 2H + 5H, C5H4, C5H5), 4.51 (m, 2H, C5H4), 7.25 (m, 4H,
C6H4),7.53(m,4H,C6H4).13CNMR(DMSO-d6)d:29.70(CH2CH2CH2),
34.63 (CH2COOH), 34.63 (CH2C6H4), 85.66 and 88.98 (CºC), 66.84
(2C, C5H4), 69.99 (C5H5), 71.42 (2C, C5H4), 125.29, 125.71, 126.76,
126.97, 129.00, 131.77, 138.28, 140.62 (Ar). MS (MALDI-TOF), m/z:
448.114 [M+] (calc., m/z: 448.1126). Found (%): C, 75.16; H, 5.78. Calc.
for C28H24O2Fe (%): C, 75.01; H, 5.39.
and 8.17–8.19 (m, 4H, AA'BB', C6H4). 13C NMR (CDCl3) d: 64.88 (Cipso
,
C5H4), 69.07 (CH, C5H4), 70.05 (CH, C5H5), 71.57 (CH, C5H4), 85.95,
94.50 (CºC), 128.30 (Cipso, C6H4), 130.80 (Cipso, C6H4), 133.36 (CH,
C6H4), 135.45 (CH, C6H4). MS (MALDI-TOF), m/z: 936.120 [M+] (calc.,
m/z: 936.1226). Found (%): C, 69.19; H, 4.29. Calc. for C54H39Fe3B3O3
(%): C, 69.30; H, 4.20.
‡
4-(4'-Ferrocenylethynyl[1,1']biphenyl-4-yl)butanoic acid 28. A mixture
§
of boroxine 11 (0.168 g, 0.18 mmol), iodoarene 14 (0.157 g, 0.54 mmol),
potassium carbonate (0.193 g, 1.35 mmol), Pd(PPh3)4 (0.017 g, 0.015 mmol),
DMF (10 ml) and 1 ml of water was stirred at 60°C for 12 h in argon
purge. After cooling to ambient temperature, the mixture was poured into
Although the reactants were consumed during cross-coupling, puri-
fication of the terphenyl products was impossible due to their very low
solubility. However, MALDI data confirmed formation of cross-coupling
products.
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Mendeleev Commun., 2015, 25, 111–113
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Received: 7th August 2014; Com. 14/4442
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