Synthesis of N-[3-alkoxy-4-(hydroxy-, alkoxy-, or acyloxy)-benzylidene- and -phenylmethyl]biphenyl-2-amines

Article abstract of DOI:10.1134/S1070363209050156

Condensation of aldehydes of the vanillin series (vanillin, vanillal, and ethers and esters derived therefrom) with biphenyl-2-amine in anhydrous methanol gave the corresponding Schiff bases which were reduced with Na[BH(OAc) ₃] in benzene under mild conditions to obtain N-[3-alkoxy-4-(hydroxy- , alkoxy-, or acyloxy)phenylmethyl]biphenyl-2-amines.

Full text of DOI:10.1134/S1070363209050156

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 5, pp. 957–961. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © E.A. Dikusar, V.I. Potkin, N.A. Zhukovskaya, N.G. Kozlov, A.P. Yuvchenko, 2009, published in Zhurnal Obshchei Khimii, 2009,
Vol. 79, No. 5, pp. 785–789.
Synthesis of N-[3-Alkoxy-4-(hydroxy-, alkoxy-, or acyloxy)-
benzylidene- and -phenylmethyl]biphenyl-2-amines
E. A. Dikusara, b, V. I. Potkina, N. A. Zhukovskayaa, N. G. Kozlova, b, and A. P. Yuvchenkob
a Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus,
ul. Surganova 13, Minsk, 220072 Belarus
e-mail: evgen_58@mail.ru
b Institute of New Materials Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus
e-mail: mixa@ichnm.basnet.by
Received July 1, 2008
Abstract—Condensation of aldehydes of the vanillin series (vanillin, vanillal, and ethers and esters derived
therefrom) with biphenyl-2-amine in anhydrous methanol gave the corresponding Schiff bases which were
reduced with Na[BH(OAc)3] in benzene under mild conditions to obtain N-[3-alkoxy-4-(hydroxy-, alkoxy-, or
acyloxy)phenylmethyl]biphenyl-2-amines.
DOI: 10.1134/S1070363209050156
We previously reported on the synthesis of N-[(E)-
3-alkoxy-4-acyloxyphenylmethylidene)biphenyl-4-
amines (Schiff bases) by condensation of biphenyl-4-
amine with esters derived from vanillin and vanillal
[1–3]. Aromatic Schiff bases of the vanillin series
attract interest as materials for the preparation of
nanofilms and nanomaterials [4].
The structure of Schiff bases IIIa–IIIu and IVa–
IVm and secondary amines Va–Vu and VIa–VIm was
confirmed by elemental analysis, cryoscopic deter-
mination of molecular weight (see Table 1), and IR and
1H NMR spectroscopy. According to the 1H NMR data,
the purity of the isolated compounds was 95±1%.
Compounds IIIa–IIIu, IVa–IVm, Va–Vu, and
VIa–VIm are colored (mostly yellow) viscous glassy
or crystalline substances which are soluble in benzene,
chloroform, and acetone and insoluble in water and
hexane. Secondary amines Va–Vu and VIa–VIm,
especially those containing hydroxy groups (com-
pounds Va and VIa), are unstable; they quickly darken
on exposure to light and atmospheric oxygen as a
result of oxidation with formation of tarry products.
These compounds can be stored for a long time in
sealed ampules under argon in the dark at reduced
temperature.
The goal of the present work was to develop a
preparative procedure for the synthesis of new
aromatic Schiff bases containing hydroxy groups and
ether or ester moieties. By condensation of biphenyl-2-
amine with vanillin, vanillal, and their ethers and esters
on heating in boiling anhydrous methanol we obtained
the corresponding aromatic Schiff bases IIIa–IIIu and
IVa–IVm which were isolated in 82–91% yield. The
reactions were complete in 10–15 min under mild
conditions in the absence of a catalyst, so that labile
ester groups were conserved.
Schiff bases IIIa–IIIu and IVa–IVm were
subjected to mild reduction with sodium triacetoxy-
hydridoborate Na[BH(OAc)3] in benzene at 20–23°C.
The reactions were complete in 18–20 h, and the
products were the corresponding secondary amines Va–
Vu and VIa–VIm; their yields were almost quanti-
tative (93–96%). The reduction of the azomethine
bond [5] was not accompanied by side reduction or
hydrolysis of ester groups (Scheme 1).
The IR spectra of compounds III–VI contained
absorption bands due to stretching vibrations of
aromatic C–H bonds (3100–3000, δ 880–700 cm–1),
aliphatic C–H bonds (3000–2840 cm–1), carbonyl
groups (1770–1720 cm–1), aromatic C=C bonds (1600–
1370 cm–1), and C–O bonds (1280–1035 cm–1). In the
IR spectra of Schiff bases IIIa–IIIu and IVa–IVm we
observed an absorption band at 1632–1618 cm–1,
which is typical of stretching vibrations of azomethine
957

958
DIKUSAR et al.
Scheme 1.
NH2
CHO
Na[BH(OAc)3]
H
N
C
+
NH
H2C
RO
OR'
RO
RO
OR'
IIIa_IIIu, IVa_IVm
OR'
Va_Vu, VIa_VIm
I
II
III, V, R = Me, R′ = H (a), Me (b), MeC(O) (c), EtC(O) (d), PrC(O) (e), Me2CHC(O) (f), Me(CH2)6C(O) (g), Me(CH2)8C(O)
(h), Me(CH2)16C(O) (i), H2C=C(Me)C(O) (j), PhCH2C(O) (k), PhCH(Me)CH2C(O) (l), PhC(O) (m), 4-ClC6H4C(O) (n), 2,4-
Cl2C6H3C(O) (o), 4-BrC6H4C(O) (p), 3-O2NC6H4C(O) (q), MeOC(O) (r), EtOC(O) (s), 1/2 [(O)C(CH2)2C(O)] (t),
m-HCB10H10CC(O) (u); IV, VI, R = Et, R′ = H (a), Me (b), MeC(O) (c), EtC(O) (d), PrC(O) (e), Me2CHC(O) (f),
Me2CHCH2C(O) (g), 4-MeC6H4C(O) (h), 3,5-(O2N)2C6H3C(O) (i), MeOC(O) (j), EtOC(O) (k), 1/2 [(O)C(CH2)2C(O)] (l),
m-HCB10H10CC(O) (m).
C=N bond; no such band was present in the spectra of
secondary amines Va–Vu and VIa–VIm. In contrast,
amines V and VI characteristically displayed absorp-
tion in the region 3450–3390 cm–1 due to stretching
vibrations of the N–H bond. In addition, the IR spectra
of nitro-substituted derivatives IIIq, IVi, Vq, and VIi
contained absorption bands belonging to symmetric
and antisymmetric vibrations of the nitro group (1532–
1528 and 1350–1344 cm–1), while m-carborane deriva-
tives IIIu, IVm, Vu, and VIm showed absorption
bands at 3065–3063 (C–H) and 2680–2500 cm–1
(B–H).
Table 1. Yields, melting points, elemental analyses, and molecular weights of Schiff bases IIIa–IIIu and IVa–IVm and
secondary amines Va–Vu and VIa–VIm
Found, %
H
Calculated, %
H
M
Comp. Yield,
mp, °C
Formula
no.
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
%
C
N
C
N
found
292.8
310.3
338.1
352.7
365.0
366.2
421.3
448.2
557.4
362.4
415.9
440.2
398.6
429.0
465.3
calculated
82
88
90
89
91
91
90
87
84
82
83
85
88
90
86
–
79.44
79.63
76.82
77.09
77.43
77.45
78.83
79.04
80.35
77.82
80.08
80.44
79.87
73.58
68.34
5.67
6.12
5.60
6.01
6.25
6.19
7.41
7.79
9.22
5.76
5.53
6.16
5.34
4.73
4.13
4.43
4.15
3.86
3.72
3.58
3.54
2.97
2.85
2.19
3.54
3.05
2.76
3.18
2.71
2.63
C20H17NO2
C21H19NO2
C22H19NO3
C23H21NO3
C24H23NO3
C24H23NO3
C28H31NO3
C30H35NO3
C38H51NO3
C24H21NO3
C28H23NO3
C30H27NO3
C27H21NO3
C27H20ClNO3
C27H19Cl2NO3
79.19
79.47
76.50
76.86
77.19
77.19
78.29
78.74
80.10
77.61
79.79
80.15
79.59
73.38
68.08
5.65
6.03
5.54
5.89
6.21
6.21
7.27
7.71
9.02
5.70
5.50
6.05
5.19
4.56
4.02
4.62
4.41
4.06
3.90
3.75
3.75
3.26
3.06
2.46
3.77
3.32
3.12
3.44
3.17
2.94
303.4
317.4
345.4
359.4
373.5
373.5
429.6
457.6
569.8
371.4
421.5
449.5
407.5
441.9
476.4
–
–
82–83
–
–
IIIg
IIIh
IIIi
–
55–56
76–77
–
IIIj
IIIk
IIIl
–
73–74
132–133
150–151
94–95
IIIm
IIIna
IIIob
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 5 2009

SYNTHESIS OF N-[3-ALKOXY-4-(HYDROXY-, ALKOXY-, OR ACYLOXY)-
959
Table 1. (Contd.)
Found, %
H
Calculated, %
H
M
Comp. Yield,
mp, °C
Formula
no.
IIIpc
IIIq
IIIr
IIIs
IIIt
IIIud
IVa
IVb
IVc
IVd
IVe
IVf
IVg
IVh
IVi
IVj
IVk
IVl
IVme
Va
%
C
N
C
N
found
473.1
438.6
354.2
368.4
669.8
464.5
312.0
325.3
350.2
362.5
374.3
378.7
388.2
420.6
496.8
366.3
376.4
698.0
478.5
292.4
307.8
336.0
350.5
363.8
361.9
413.2
450.1
562.2
360.0
412.3
435.6
398.2
430.4
466.3
467.7
450.2
348.7
360.1
calculated
89
91
88
88
87
83
84
85
86
87
88
86
88
91
90
86
83
90
89
93
95
94
94
94
93
96
94
94
93
96
94
93
93
94
95
96
95
95
160–161
66.93
71.92
73.36
73.83
76.99
58.61
79.64
80.09
77.01
77.35
77.82
77.73
77.98
80.21
65.86
73.67
74.24
77.25
59.43
78.87
79.18
76.35
76.68
77.05
76.94
78.12
78.67
80.06
77.43
79.85
80.05
79.50
73.26
68.12
66.49
71.58
72.94
73.51
4.26
4.55
5.39
5.72
5.31
5.84
6.12
6.45
6.04
6.32
6.50
6.62
6.85
5.93
4.28
5.74
6.10
5.73
6.17
6.36
6.67
6.20
6.62
6.78
6.70
7.79
8.24
9.60
6.32
6.08
6.57
5.73
5.12
4.44
4.61
5.00
5.98
6.18
2.56
5.84
3.57
3.48
3.77
2.70
4.18
4.00
3.66
3.64
3.43
3.40
3.22
2.99
7.94
3.38
3.32
3.55
2.54
4.23
4.06
3.84
3.64
3.44
3.41
2.98
2.69
2.42
3.62
3.03
2.85
3.19
2.80
2.57
2.53
5.85
3.43
3.50
C27H20BrNO3
C27H20N2O5
C22H19NO4
C23H21NO4
C44H36N2O6
C23H27B10NO3
C21H19NO2
C22H21NO2
C23H21NO3
C24H23NO3
C25H25NO3
C25H25NO3
C26H27NO3
C29H25NO3
C28H21N3O7
C23H21NO4
C24H23NO4
C46H40N2O6
C24H29B10NO3
C20H19NO2
C21H21NO2
C22H21NO3
C23H23NO3
C24H25NO3
C24H25NO3
C28H33NO3
C30H37NO3
C38H53NO3
C24H23NO3
C28H25NO3
C30H29NO3
C27H23NO3
C27H22ClNO3
C27H21Cl2NO3
C27H22BrNO3
C27H22N2O5
C22H21NO4
C23H23NO4
66.68
71.67
73.12
73.58
76.73
58.33
79.47
79.73
76.86
77.19
77.49
77.49
77.78
79.98
65.75
73.58
74.02
77.08
59.12
78.66
78.97
76.06
76.43
76.77
76.77
77.93
78.40
79.82
77.19
79.41
79.80
79.20
73.05
67.79
66.40
71.36
72.71
73.19
4.14
4.46
5.30
5.64
5.27
5.75
6.03
6.39
5.89
6.21
6.50
6.50
6.78
5.79
4.14
5.64
5.95
5.62
5.99
6.27
6.63
6.09
6.41
6.71
6.71
7.73
8.11
9.34
6.21
5.95
6.47
5.66
4.99
4.42
4.54
4.88
5.82
6.14
2.88
6.19
3.88
3.73
4.07
2.96
4.41
4.23
3.90
3.75
3.61
3.61
3.49
3.22
8.22
3.73
3.60
3.91
2.87
4.59
4.39
4.03
3.88
3.73
3.73
3.25
3.05
2.45
3.75
3.31
3.10
3.42
7.99
2.93
2.87
6.16
3.85
3.71
486.3
452.5
361.4
375.4
688.8
473.6
317.4
331.4
359.4
373.5
387.5
387.5
401.5
435.5
511.5
375.4
389.5
716.8
487.6
305.4
319.4
347.4
361.4
375.5
375.5
431.6
459.6
571.8
373.5
423.5
451.6
409.5
443.9
478.4
488.4
454.5
363.4
377.4
64–65
47–48
101–102
183–184
141–142
102–103
–
–
–
–
–
–
137–138
136–137
–
51–52
115–116
90–91
–
Vb
–
Vc
–
Vd
65–66
Ve
–
Vf
–
Vg
–
Vh
–
54–55
–
Vi
Vj
Vk
–
Vl
52–53
–
Vm
Vnf
Vog
Vph
Vq
128–129
77–78
138–139
–
Vr
–
Vs
82–83
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 5 2009

960
DIKUSAR et al.
Table 1. (Contd.)
Found, %
Calculated, %
H
M
Comp.
no.
Yield,
%
mp, °C
Formula
N
C
H
C
N
found
675.8
458.2
312.3
324.4
350.2
363.8
380.0
378.4
391.1
419.3
489.4
364.4
calculated
692.8
475.6
319.4
333.4
361.4
375.5
389.5
389.5
403.5
437.5
513.5
377.4
Vt
Vui
96
94
93
93
95
95
94
94
93
96
95
94
162–163
76.53
58.38
79.16
79.46
76.83
77.01
77.34
77.42
77.90
79.83
65.84
73.45
5.97
6.23
6.64
7.00
6.48
6.82
7.15
7.20
7.34
6.32
4.63
6.27
3.72
2.45
4.04
3.98
3.49
3.40
3.19
3.20
3.18
2.95
7.86
3.46
C44H40N2O6
C23H29B10NO3
C21H21NO2
C22H23NO2
C23H23NO3
C24H25NO3
C25H27NO3
C25H27NO3
C26H29NO3
C29H27NO3
C28H23N3O7
C23H23NO4
76.28
58.08
78.97
79.25
76.43
76.77
77.09
77.09
77.39
79.61
65.49
73.19
5.82
6.15
6.63
6.95
6.41
6.71
6.99
6.99
7.24
6.22
4.51
6.14
4.04
2.95
4.39
4.20
3.88
3.73
3.60
3.60
3.47
3.20
8.18
3.71
124–125
VIa
VIb
VIc
VId
VIe
VIf
VIg
VIh
VIi
VIj
84–85
–
–
–
–
–
–
115–116
117–118
–
VIk
93
94
93
–
73.84
76.93
59.11
6.55
6.19
6.46
3.23
3.80
2.52
C24H25NO4
73.64
76.65
58.87
6.44
6.15
6.38
3.58
3.89
2.86
381.4
698.3
469.7
391.5
720.9
489.6
VIl
94–95
82–83
C46H44N2O6
C24H31B10NO3
VImj
a
c
Found Cl, %: 7.86. Calculated Cl, %: 8.02. b Found Cl, %: 14.60. Calculated Cl, %: 14.88. Found Br, %: 16.14. Calculated Br, %:
16.43. d Found B, %: 22.44. Calculated B, %: 22.83. e Found B, %: 21.86. Calculated B, %: 22.17. f Found Cl, %: 7.58. Calculated Cl, %:
7.99. g Found Cl, %: 14.53. Calculated Cl, %: 14.82. h Found Br, %: 16.11. Calculated Br, %: 16.36. i Found B, %: 22.28. Calculated B,
%: 22.73. j Found B, %: 2184. Calculated B, %: 22.08.
1
In the H NMR spectra of IIIa–IIIu, IVb, Va–Vu,
EXPERIMENTAL
and VIb, protons in the methoxy group resonated as a
singlet in the region δ 3.78–3.93 ppm, while protons of
the ethoxy group in compounds IVa–IVm and VIa–
VIm gave a triplet at δ 1.15–1.45 ppm (CH3) and a
quartet at δ 3.90–4.20 ppm (CH2). Signals from aro-
matic protons were located in the δ range from 6.90 to
7.60 ppm, and the azomethine proton signal appeared
The IR spectra were recorded in KBr on a Nicolet
Protégé-460 spectrometer with Fourier transform. The
1H NMR spectra were measured on a Tesla BS-587A
instrument (100 MHz) from 5% solutions in CDCl3;
the chemical shifts were determined relative to
tetramethylsilane as internal reference. The elemental
analyses were obtained on a VarioEL-III CHNOS
analyzer with an accuracy of ±0.1%. The molecular
weights were determined by cryoscopy in benzene.
1
in the H NMR spectra of Schiff bases IIIa–IIIu and
IVa–IVm as a singlet at δ 8.42–8.50 ppm, which is
typical of E isomers [6]. Secondary amines Va–Vu and
1
VIa–VIm displayed in the H NMR spectra signals
The initial vanillin and vanillal esters were
synthesized according to the procedures described in
[8–11].
from protons in the CH2NH group as a broadened
singlet at δ 4.36–4.38 ppm. Signals from the carborane
CH protons in m-carborane derivatives IIIu, IVm, Vu,
and VIm were located at δ 3.00–3.05 ppm (broadened
singlet).
N-[(E)-3-Alkoxy-4-(hydroxy, alkoxy, or acyloxy)
benzylidene]biphenyl-2-amines IIIa–IIIu and IVa–
IVm (general procedure). A solution of 5 mmol of the
corresponding aldehyde I and 5 mmol of biphenyl-2-
amine (II) in 30 ml of anhydrous methanol was heated
for 10–15 min. The hot solution was filtered through a
folded paper filter, the filtrate was cooled and left to
Wide homologous series of Schiff bases and
secondary amines III–VI based on biphenyl-2-amine
(II) are necessary for detailed study on the effect of the
R and R1 substituents on the topology of nanofilms
prepared from these compounds [7].
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 5 2009

SYNTHESIS OF N-[3-ALKOXY-4-(HYDROXY-, ALKOXY-, OR ACYLOXY)-
961
vanilalya (Schiff Bases Derived from Vanillin and
Vanillal), Karakalpakstan: Nukus, 2007.
stand for 10–15 h at 5°C, and the precipitate was
filtered off through a glass porous filter or separated by
decanting, washed with a small amount of methanol,
and dried in air.
4. Azarko, V.A., Dikusar, E.A., Potkin, V.I., Kozlov, N.G.,
and Yuvchenko, A.P., Materialy mezhdunarodnoi
nauchno-prakticheskoi konferentsii “Optika neodno-
rodnykh struktur–2007” (Proc. Int. Scientific–Practical
Conf. “Optics of Heterogeneous Structures–2007”),
Mogilev: Mogilev. Gos. Univ. Imeni A.A. Kuleshova,
2007, p. 27.
N-[3-Alkoxy-4-(hydroxy, alkoxy, or acyloxy)
phenylmethyl]biphenyl-2-amines Va–Vu and VIa–
VIm (general procedure). A mixture of 5 mmol of
Schiff base IIIa–IIIu or IVa–IVm, 10 mmol of
NaBH4, 30 mmol of glacial acetic acid, and 50 ml of
anhydrous benzene was left to stand for 18–20 h. The
solution was washed with water and a 5% solution of
NaHCO3, the solvent was removed under reduced
pressure, and the residue was purified by recrys-
tallization from benzene–hexane or by column chro-
matography on silica gel (100–160 μm) using benzene
as eluent.
5. Esteves-Souza, A., Echevarria, A., and Sant’Anna, C.M.R.,
Quim. Nova, 2004, vol. 27, no. 1, p. 72.
6. Dyer, J.R., Applications of Absorption Spectroscopy of
Organic Compounds, Englewood Cliffs: Prentice–Hall,
1965. Translated under the title Prilozheniya absor-
btsionnoi spektroskopii organicheskikh soedinenii,
Moscow: Khimiya, 1970, p. 92.
7. Wiesner, M. and Bottero, J.-Y., Environmental
Nanotechnology, New York: McGraw-Hill, 2007.
8. Dikusar, E.A., Vyglazov, O.G., Moiseichuk, K.L.,
Zhukovskaya, N.A., and Kozlov, N.G., Zh. Prikl. Khim.,
2005, vol. 78, no. 1, p. 122.
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 5 2009