Synthesis of o(m)-carborane-containing azomethines

Article abstract of DOI:10.1134/S1070363212030085

A method of preparative synthesis of o(m)-carborane-containing azomethines via the condensation of o(m)-carboranyl-C-methylene-4-formylbenzoates with aliphatic, cycloaliphatic, and aromatic amines was developed. Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S1070363212030085

ISSN 1070-3632, Russian Journal of General Chemistry, 2012, Vol. 82, No. 3, pp. 413–416. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © E.A. Dikusar, V.I. Potkin, D.A. Rudakov, T.D. Zvereva, S.K. Petkevich, M.M. Ogorodnikova, A.P. Yuvchenko, M.P. Bei, 2012,
published in Zhurnal Obshchei Khimii, 2012, Vol. 82, No. 3, pp. 420–423.
Synthesis of o(m)-Carborane-Containing Azomethines
E. A. Dikusara,b, V. I. Potkina, D. A. Rudakova, T. D. Zverevaa, S. K. Petkevicha,
M. M. Ogorodnikovaa, A. P. Yuvchenkob, and M. P. Beib
a Institute of Physical Organic Chemistry of National Academy of Sciences of Belarus,
ul. Surganova 13, Minsk, 220072 Belarus
e-mail: dikusar@ifoch.bas-net.by
bInstitute of Chemistry of New Materials of National Academy of Sciences of Belarus, Minsk, Belarus
Received January 18, 2011
Abstract—A method of preparative synthesis of o(m)-carborane-containing azomethines via the condensation
of о(m)-carboranyl-С-methylene-4-formylbenzoates with aliphatic, cycloaliphatic, and aromatic amines was
developed.
DOI: 10.1134/S1070363212030085
Previously we have reported on the synthesis of
o(m)-carborane-containing Schiff bases via the con-
densation of vanillin esters of o(m)-carborane-C-car-
boxylic acid and vanillin with amines [1–4]. The car-
borane nitrogen-containing derivatives are of interest
for research in the field of the boron neutron capture
therapy of the tumor diseases, radionuclide diagnostics
and therapy [5, 6].
In this work we describe the method of preparative
synthesis of new o(m)-carborane azomethines IVa–
IVz' and Va–IVz' by the condensation of o(m)-
R
H
N
CHO
C
4-HC(O)C6H4C(O)Cl, Py
H2NR
o(m)-HCB10H10CCH2OH
−Py
HCl
C(O)OCH2CB10H10CH-o(m)
C(O)OCH2CB10H10CH-o(m)
Iа, Ib
IVа−IVz', Vа−Vz'
IIIа, IIIb
N
N(CH2)3
HC
HC
H
Me
N
O
2
2
C(O)CB10H10CH-o(m)
C(O)CB10H10CH-o(m)
IVx', Vx'
IVy, Vy
IVy', IVz', Vy', Vz'
Iа, IIIа, IVа– IVz' are о-carborane derivatives; Ib, IIIb, Vа–Vz' are m-carborane derivatives; IV, V: R = n-C16H33 (a), n-
C18H37 (b), cyclo-С6H11 (c), СH(1-Ad)Me (d), L-CH(CHMe2)CO2Me (e), L-CH(CHCH2Me2)CO2Me (f), L-CH(CHMeEt)
CO2Me (g), L-CH(CH2Ph)CO2Me (h), 4-MeC6H4 (i), 2-biphenyl (j), 4-biphenyl (k), 1-naphthyl (l), 2-naphthyl (m), 3-
BrC6H4 (n), 4-BrC6H4 (o), 4-IC6H4 (p), 1-bromo-2-naphthyl (q), 2-hydroxyphenyl (r), 4-phenoxyphenyl (s), 4-EtC(O)C6H4
(t), 3-HO2CC6H4 (u), 4-HO2CC6H4 (v), 4-EtO2CC6H4 (w), 4-BuO2CC6H4 (x); IVx', Vx' are 1,6-hexamethylene diamine
derivatives; IVy', IVz' , Vy', Vz' are 1,3- and 1,4-phenylene diamine derivatives.
413

414
DIKUSAR et al.
carborane-C-methyl-4-formylbenzoates IIIa and IIIb
with aliphatic, cycloaliphatic, and aromatic amines
IIa–IIz'. The yields of compounds IVa– IVz' and Va–
IVz' were 82–88%.
chloride in the presence of pyridine [7]. The yields of
compounds IIIa and IIIb were 88–90%.
The obtained carborane-containing compounds III,
IV, and V are crystalline or amorphous glassy substances,
which are soluble in DMF, DMSO, and CHCl3. The struc-
ture of the obtained compounds was confirmed by the
elemental analysis, IR and NMR spectroscopy (see the
table).
The starting o(m)-carborane-C-methylene-4-formyl-
benzoates III were synthesized by the esterification of
o(m)-carborane-C-methanols I with 4-formylbenzoyl
Yields, melting points, and elemental analysis data for compounds III, IV and V
Found, %
Calculated, %
М
Comp. Yield,
mp,
°С
Formula
no.
%
С
H
B
N
С
H
B
N
found calculated
88
77–78
43.38
6.14 35.02
6.99 34.96
9.87 20.05 2.19 C27H51B10NO2
–
–
C11H18B10O3
C11H18B10O3
43.12 5.92 35.29
43.12 5.92 35.29
–
–
299.0
297.5
306.4
IIIa
90
83
84
87
88
88
86
86
87
82
85–86
37–38
38–39
–
–
–
–
–
–
43.44
61.65
306.4
529.8
557.9
387.5
467.7
419.5
433.6
433.6
467.6
395.5
IIIb
IVa
IVb
IVc
IVd
IVe
IVf
IVg
IVh
IVi
61.21 9.70 20.41 2.64 504.7
62.44 9.94 19.38 2.51 538.4
52.69 7.54 27.90 3.61 359.6
59.07 7.97 23.12 3.00 460.0
48.67 6.97 25.77 3.34 404.2
49.87 7.21 24.94 3.23 409.6
49.87 7.21 24.94 3.23 412.8
53.94 6.25 23.12 3.00 448.3
54.66 6.37 27.33 3.54 382.2
62.73 10.08 18.95 2.04 C29H55B10NO2
52.99
59.52
48.98
50.17
50.08
54.23
54.94
7.67 27.60 3.21 C17H29B10NO2
8.14 22.76 2.88 C23H37B10NO2
7.19 25.38 3.05 C17H29B10NO4
7.42 24.65 2.90 C18H31B10NO4
7.39 24.61 2.99 C18H31B10NO4
6.41 22.86 2.80 C21H29B10NO4
6.53 27.01 3.28 C18H25B10NO2
81–82
85
88
143–144 60.72
172–173 60.80
6.18 23.10 2.86 C23H27B10NO2
6.22 23.28 2.90 C23H27B10NO2
60.37 5.95 23.63 3.06 441.4
60.37 5.95 23.63 3.06 448.1
457.6
457.6
IVj
IVk
86
86
84
86
85
84
107–108 58.75
164–165 58.89
6.00 24.81 2.92 C21H25B10NO2
6.08 24.73 2.99 C21H25B10NO2
4.97 23.11 2.63 C17H22B10BrNO2
5.03 23.07 2.85 C17H22B10BrNO2
3.51 10.96 2.46 C17H22B10INO2
4.94 20.85 2.30 C21H24B10BrNO2
58.45 5.84 25.05 3.25 420.3
58.45 5.84 25.05 3.25 418.7
44.35 4.82 23.48 3.04 443.7
44.35 4.82 23.48 3.04 451.9
40.24 4.37 21.31 2.76 484.2
49.41 4.74 21.18 2.74 497.6
431.5
431.5
460.4
460.4
507.4
510.4
IVl
IVm
IVna
IVob
IVрc
IVqd
–
44.62
150–151 44.70
175–176 40.25
126–127 49.12
88
87
86
85
88
83
84
87
83
83
85
85
82
84
88
84
171–172 51.64
5.98 26.76 3.13 C17H23B10NO3
5.90 22.53 2.40 C23H27B10NO3
6.50 24.28 2.83 C20H27B10NO3
5.62 25.03 2.87 C18H23B10NO4
5.71 25.20 2.94 C18H23B10NO4
6.24 23.51 2.86 C20H27B10NO4
6.72 22.07 2.56 C22H31B10NO4
5.66 22.88 5.83 C21H26B10N2O3
7.19 30.79 3.75 C28H48B20N2O4
6.00 31.23 3.76 C28H40B20N2O4
6.07 31.20 3.88 C28H40B20N2O4
9.74 20.22 2.35 C27H51B10NO2
51.37 5.83 27.20 3.52 381.0
58.33 5.75 22.83 2.96 458.4
54.90 6.22 24.71 3.20 418.8
50.81 5.45 25.41 3.29 446.2
50.81 5.45 25.41 3.29 451.0
52.96 6.00 23.84 3.09 436.1
54.87 6.49 22.45 2.91 460.3
54.53 5.67 23.37 6.06 448.3
48.53 6.98 31.20 4.04 667.5
49.11 5.89 31.57 4.09 655.9
49.11 5.89 31.57 4.09 668.3
61.21 9.70 20.41 2.64 512.5
62.44 9.94 19.38 2.51 543.2
52.69 7.54 27.90 3.61 364.4
59.07 7.97 23.12 3.00 458.1
48.67 6.97 25.77 3.34 412.2
397.5
473.6
437.5
425.5
425.5
453.5
481.6
462.6
692.9
684.9
684.9
529.8
557.9
387.5
467.7
419.5
IVr
IVs
IVt
IVu
IVv
IVw
IVx
IVy
IVx'
IVy'
IVz'
Va
86–87
–
58.51
55.43
168–169 51.15
272–273 51.19
–
53.32
164–165 55.15
218–219 54.83
–
–
48.87
49.19
264–265 49.49
37–38
61.66
39–40
62.59 10.27 18.90 2.25 C29H55B10NO2
Vb
Vc
Vd
–
–
–
52.14
59.60
48.92
7.67 27.51 3.30 C17H29B10NO2
8.21 22.72 2.50 C23H37B10NO2
7.15 25.65 2.98 C17H29B10NO4
Ve
86
85
85
–
–
–
50.30
50.17
54.42
7.23 24.45 2.90 C18H31B10NO4
7.44 24.63 2.76 C18H31B10NO4
6.48 22.70 2.67 C21H29B10NO4
49.87 7.21 24.94 3.23 414.5
49.87 7.21 24.94 3.23 423.4
53.94 6.25 23.12 3.00 451.6
433.6
433.6
467.6
Vf
Vg
Vh
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 3 2012

415
SYNTHESIS OF o(m)-CARBORANE-CONTAINING AZOMETHINES
(Contd.)
Found, %
Calculated, %
М
Comp. Yield,
mp,
°С
Formula
no.
%
С
H
B
N
С
H
B
N
found
calculated
86
84
85
87
88
83
85
85
84
85
86
86
86
84
84
85
86
82
83
84
127–128 54.23
60.66
6.48 27.01 3.18 C18H25B10NO2
6.21 23.17 2.50 C23H27B10NO2
6.17 23.06 2.84 C23H27B10NO2
6.02 24.75 2.92 C21H25B10NO2
5.88 24.92 3.03 C21H25B10NO2
5.05 23.40 2.82 C17H22B10BrNO2
5.01 23.00 2.81 C17H22B10BrNO2
4.57 20.91 2.40 C17H22B10INO2
5.02 20.73 2.44 C21H24B10BrNO2
6.10 26.84 3.12 C17H23B10NO3
5.81 22.48 2.56 C23H27B10NO3
6.28 24.25 2.78 C20H27B10NO3
5.64 25.08 2.90 C18H23B10NO4
5.63 25.30 3.14 C18H23B10NO4
6.21 23.25 2.61 C20H27B10NO4
6.58 22.13 2.56 C22H31B10NO4
5.80 23.05 5.67 C21H26B10N2O3
7.34 30.72 3.78 C28H48B20N2O4
5.94 31.16 3.76 C28H40B20N2O4
5.80 31.27 4.02 C28H40B20N2O4
54.66 6.37 27.33 3.54 385.2
60.37 5.95 23.63 3.06 449.0
60.37 5.95 23.63 3.06 447.4
58.45 5.84 25.05 3.25 422.8
58.45 5.84 25.05 3.25 416.4
44.35 4.82 23.48 3.04 444.2
44.35 4.82 23.48 3.04 454.7
40.24 4.37 21.31 2.76 488.2
49.41 4.74 21.18 2.74 494.3
51.37 5.83 27.20 3.52 381.9
58.33 5.75 22.83 2.96 456.2
54.90 6.22 24.71 3.20 428.7
50.81 5.45 25.41 3.29 443.4
50.81 5.45 25.41 3.29 454.2
52.96 6.00 23.84 3.09 445.4
54.87 6.49 22.45 2.91 468.8
54.53 5.67 23.37 6.06 449.5
48.53 6.98 31.20 4.04 675.1
49.11 5.89 31.57 4.09 668.6
49.11 5.89 31.57 4.09 677.2
395.5
457.6
457.6
431.5
431.5
460.4
460.4
507.4
510.4
397.5
473.6
437.5
425.5
425.5
453.5
481.6
462.6
692.9
684.9
684.9
Vi
–
Vj
191–192 60.75
171–172 58.86
124–125 58.90
Vk
Vl
Vm
Vne
Vof
Vpg
Vqh
Vr
–
44.58
136–137 44.69
146–147 40.40
–
49.85
163–164 51.24
108–109 58.57
Vs
–
55.36
Vt
187–188 51.19
275–276 50.99
Vu
Vv
Vw
Vx
Vy
Vx'
Vy'
Vz'
–
–
53.50
55.16
229–230 54.91
–
–
48.98
49.49
252–253 49.19
Found Br, %: 16.92. Calculated Br, %: 17.36. b Found Br, %: 16.99. Calculated Br, %: 17.36. c Found I, %: 24.76. Calculated I, %: 25.01.
d Found Br, %: 15.23. Calculated Br, %: 15.65. e Found Br, %: 16.84. Calculated Br, %: 17.36. f Found Br, %: 16.90. Calculated Br, %:
17.36. g Found I, %: 24.73. Calculated I, %: 25.01. h Found Br, %: 15.36. Calculated Br, %: 15.65.
a
The IR spectra of carborane-containing aldehydes
EXPERIMENTAL
IIIа and IIIb and azomethines IVа–IVz' and Vа–Vz'
contain the following characteristic absorption bands
(ν, cm–1): 3060±4 (С–Нcarb), 2590±15 (B–H), 1730±5
(C=Oester), 1615±5, 1580±5, 1415±5 (С=СAr), 1265±5,
1105±5, 1015±5 (С–О), 840±5, 755±5, 720±5
(С–НAr), 1706±1 (C=Oald), 1633±13 (С=N).
The IR spectra were recorded on a Nicolet Protégé-
460 Fourier-spectrometer (from film or pellets with
KBr). The 1Н NMR spectra were registered on a Tesla
BS-587A spectrometer (100 MHz) for 5% DMSO-d6
1
solutions relative to internal TMS (IV, V); the Н and
11В NMR spectra (IVo, Vo), on a Bruker Avance-500
1
The Н NMR spectra of о-carborane derivatives
11
spectrometer (1Н at 500 MHz and В at 160.46 MHz)
IIIа and IVа–IVz' contain the characteristic proton
signals at δ 4.9±0.2 (s, CH2O) and 5.4±0.1 ppm (br.s ,
СНcarb), of m-carborane derivatives IIIb and Vа–Vz',
at 4.1±0.1 (br.s , СНcarb) and 4.6±0.3 ppm (s, CH2O).
The aromatic protons appear in the range of 7.9–8.2
ppm (m, С6Н4). In the spectra of carborane-containing
aldehydes IIIа and IIIb there is a singlet signal of
aldehyde group at δ 10.1 ppm. The azomethine moiety
appears as a signal at δ 8.6±0.3 ppm, which is
characteristic for E-configuration of azomethines [8].
for 15% CDCl3 solutions. The molecular mass was
determined by cryoscopy in benzene.
4-Formylbenzoyl chloride [bp 282–283°С (760 mm
Hg), mp 54–55°C] was prepared by the reaction of 4-
formylbenzoic acid with 1.5 mol of SOCl2 in the
presence of catalytic amount of DMF.
4-Formylbenzoyloxymethylene-(o,m)-С-carbo-
ranes (IIIа, IIIb). To a solution of 0.1 mol (о, m)-С-
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416
DIKUSAR et al.
carboranylmethanol I and 0.1 mol of 4-formylbenzoyl
chloride in 300 ml of anhydrous diethyl ether was
added 0.1 mol of anhydrous pyridine in 50 ml of
diethyl ether within 30 min with cooling to 10–15°С
while vigorous stirring. The mixture was stirred for 1 h
and diluted with 500 ml of water. The ether layer was
separated, washed with water (3×200 ml) and saturated
NaHCO3 solution (2×200 ml), dried over MgSO4, and
concentrated. The residue was crystallized from
hexane.
144 Hz), –8.8 d (2В, В8,10, J 151 Hz), –11.0 d (2В,
В4,5, J 147 Hz), –12.4 d (4В, В3,6,7,11, J 144 Hz).
(Е)-m-Carboranyl-С-methylene-4-[(41-bromo-
1
phenyl)iminomethyl]benzoate (Vo). Н NMR spec-
trum (CDCl3), δ, ppm: 3.6–1.4 m (В10Н10), 3.00 br.s
(СНcarb), 4.55 s (CH2O), 7.11 d (J2',3' 7.1 Hz), 7.51 d
(J2',3' 7.1 Hz), 7.99 d (J2,3 7.1 Hz), 8.13 d (J2,3 7.1 Hz),
8.48 s (НC=N). 11В NMR spectrum (CDCl3), δB, ppm:
–3.8 d (1В, В5, J 163 Hz), –8.0 d (1В, В12, J 165 Hz),
–10.0 d (2В, В9,10, J 148 Hz), –11.0 d (2В, В4,6, J
159 Hz), –12.6 d (2В, В8,11, J 168 Hz), –15.1 d (2В,
В2,3, J 180 Hz).
(o,m)-Carborane-containing azomethines (IVa–
IVy, Va–Vy). A mixture of 5 mmol of 4-formyl-
benzoyloxymethylene-(o,m)-С-carborane III and
5 mmol of the corresponding secondary amine IIa–
IIx' in 40 ml of anhydrous methanol was refluxed for
30–45 min and then cooled to 0–5°С. The crystalline
azomethines were filtered off through the glass porous
filter, washed with cold methanol and dried in air for
6–8 h. The glassy azomethines were decanted and
purified by the column chromatography on a neutral
alumina (40–100 μm, Brockman activity degree II)
eluting with dichloromethane.
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(IVx'–IVz' , Vx'–Vz' ). A solution of 10 mmol of 4-
formylbenzoyloxymethylene-(o,m)-С-carborane III
and 5 mmol of the corresponding primary amine IIx'–
IIz' in 50 ml of anhydrous methanol was refluxed for
45 min. The target products were isolated similarly to
azomethines (IVa–IVy, Va–Vy).
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(СНcarb), 4.81 s (CH2O), 7.11 d (J2',3' 8.0 Hz), 7.51 d
(J2',3' 8.0 Hz), 7.99 d (J2,3 7.7 Hz), 8.11 d (J2,3 7.7 Hz),
8.48 s (НC=N). 11В NMR spectrum (CDCl3), δB, ppm:
–1.2 d (1В, В12/9, J 150 Hz), –3.8 d (1В, В9/12), J
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 3 2012