Synthesis and reactions of Schiff bases containing an m-phenoxyphenyl group: I. N-aryl-m-phenoxybenzylidene-amines and n-aryl-n′-(m-phenoxybenzylidene)hydrazines

Article abstract of DOI:10.1023/A:1012443600020

Condensation of m-phenoxybenzaldehyde with aromatic amines and hydrazines gave the corresponding Schiff bases and m-phenoxybenzaldehyde arylhydrazones. The products are promising as biologically active substances, polyfunctional additives to rubber compounds, and inhibitors of acid corrosion.

Full text of DOI:10.1023/A:1012443600020

Russian Journal of Organic Chemistry, Vol. 37, No. 5, 2001, pp. 677 679. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 5, 2001,
pp. 716 718.
Original Russian Text Copyright
2001 by Popov, Korchagina, Chicherina.
Synthesis and Reactions of Schiff Bases Containing
an m-Phenoxyphenyl Group: I. N-Aryl-m-phenoxybenzylidene-
amines and N-Aryl-N -(m-phenoxybenzylidene)hydrazines
Yu. V. Popov, T. K. Korchagina, and G. V. Chicherina
Volgograd State Technical University, pr. Lenina 28, Volgograd, 400131 Russia
Received October 4, 1999
Abstract Condensation of m-phenoxybenzaldehyde with aromatic amines and hydrazines gave the corre-
sponding Schiff bases and m-phenoxybenzaldehyde arylhydrazones. The products are promising as bio-
logically active substances, polyfunctional additives to rubber compounds, and inhibitors of acid corrosion.
Schiff bases, i.e., compounds having a double
C N bond, are used as starting materials in the syn-
thesis of important drugs, such as antibiotics and anti-
allergic, antiphlogistic, and antitumor substances
[1, 2, 3]. They are also used as components of rubber
compounds [4]. Hydrazones have found application in
synthetic and analytical chemistry, but their most
valuable property is high physiological activity [5].
The goal of the present study was to develop
procedures for synthesizing a series of new Schiff
bases and hydrazones containing an m-phenoxyphenyl
group and to find ways for their practical utilization.
m-Phenoxybenzaldehyde (I) readily reacted with
aromatic amines IIa IIp to afford the corresponding
N-aryl-m-phenoxybenzylideneamines IIIa IIIp. The
reactions started even at room temperature and were
accompanied by appreciable heat evolution: the mix-
tures warmed up by 10 15 C. However, the rate of
the condensation was low, and in 1.5 2 h the products
were formed in 60 80% yield (Scheme 1). The react-
ant molar ratio I:II was 1:1. Raising the temperature
to 60 80 C strongly accelerated the process, and the
reaction was complete in 10 15 min, but the yields
of products II did not change. Analysis of the reaction
mixtures by GLC did not reveal appreciable amounts
of by-products. By the end of the process the mixture
contained Schiff base II, water, and small amounts
of the initial reactants.
A possible reason for relatively low yields of the
condensation products in reactions of aldehyde I
with aromatic amines is equilibrium character of the
process. It is known that condensation of aldehydes
with amines is reversible [2]. We performed a series
of experiments with continuous removal of water as
azeotropic mixture with benzene. In the reactions of
I with aniline, p-anisidine, and p-bromoaniline the
theoretical amount of water separated in 50 min, but
the yields of the products slightly differed from those
obtained in the previous experiments. The yield of
N-phenyl-m-phenoxybenzylideneamine increased by
1.5%, of N-p-methoxyphenyl-m-phenoxybenzylidene-
amine, by 2%, and of N-p-bromophenyl-m-phenoxy-
benzylideneamine, by 3%. Therefore, we can conclude
that reactions of aldehyde I with aromatic amines
are almost irreversible.
Aromatic hydrazines turned out to be more reactive
toward aldehyde I, as compared with aromatic amines
[6]. The reactions readily occurred at room tempera-
Scheme 1.
R = C6H5 (a), o-O2NC6H4 (b), m-O2NC6H4 (c), p-O2NC6H4 (d), o-CH3OC6H4 (e), p-CH3OC6H4 (f), o-HOC6H4 (g), p-HOC6H4 (h),
o-CH3C6H4 (i), p-CH3C6H4 (j), p-ClC6H4 (k), p-BrC6H4 (l), 2,5-(CH3)2C6H3 (m), C6H5CH2 (n), -naphthyl (o), 2-thiazolyl (p).
1070-4280/01/3705-0677$25.00 2001 MAIK Nauka/Interperiodica

678
POPOV et al.
Yields, melting or boiling points, and elemental analyses of Schiff bases IIIa IIIp and hydrazones Va Vc
Found, %
H
Calculated, %
Comp.
no.
Yield,
%
mp, C, or bp,
C
Formula
(p, mm)
C
N
C
H
N
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
IIIj
IIIk
IIIl
IIIm
IIIn
IIIo
IIIp
Va
91
60
66
88
68
67
68
62
65
66
78
82
71
85
77
79
90
96
80
57 60
75 78
55 57
138 140
275 277 (2)
52 55
83.10
70.23
71.32
71.09
79.44
79.69
78.61
80.69
82.68
82.53
73.48
64.72
82.72
82.97
82.60
67.52
78.89
75.49
59.71
5.85
4.42
4.54
4.34
6.57
5.28
5.14
6.01
5.94
5.94
4.30
4.02
6.37
5.02
4.90
5.32
5.04
5.41
4.08
5.70
8.66
9.08
8.40
4.53
4.75
5.50
5.11
4.75
5.11
4.40
3.91
4.24
4.43
4.30
4.34
9.42
7.84
15.6
C19H15NO
83.50
71.69
71.69
71.69
79.26
79.26
79.89
79.89
83.62
83.62
74.15
64.58
83.72
83.62
83.45
68.57
79.20
75.90
60.32
5.49
4.40
4.40
4.40
5.61
5.61
5.19
5.19
5.92
5.92
4.55
3.96
6.31
5.92
5.26
4.28
5.50
5.05
3.70
5,13
8.81
8.81
8.81
4.62
4.62
4.84
4.84
4.87
4.87
4.55
3.96
4.65
4.88
4.33
10.0
9.72
8.86
14.8
C19H14N2O3
C19H14N2O3
C19H14N2O3
C20H15NO2
C20H17NO2
C19H15NO2
C19H15NO2
C20H17NO
80 82
131 133
225 228 (2)
41 42
47 49
53 55
265 267 (2)
49 51
27 30
127 129
57 59
158 160
202 204
C20H17NO
C19H14NOCl
C19H14NOBr
C21H19NO
C20H17NO
C22H17NO
C16H12N2OS
C19H16N2O
C20H16N2O2
C19H14N4O5
Vb
Vc
ture and were exothermic: the mixtures warmed up
by 30 35 C. To complete the reaction, the mixtures
were heated for 40 60 min at 60 70 C. The reactant
ratio aldehyde I:hydrazine IV was 1:1, and chloro-
form was used as solvent (Scheme 2).
The IR spectra of III and V contain a characteristic
absorption band in the region 1630 1633 cm , which
1
belongs to the C N double bond. The lack of absorp-
1
tion in the regions of 1720 and 3300 cm indicates
the absence of carbonyl and amino groups.
1
In the H NMR spectra of N-aryl-m-phenoxyben-
Scheme 2.
zylideneamines IIIa IIIp we observed an upfield
singlet at
7.90 8.20 ppm due to the CH proton.
Aromatic protons give rise to a multiplet at 6.94
7.44 ppm whose intensity corresponds to 14 protons.
The results of simulation of biological activity of
Schiff bases III and hydrazones V showed that the
potential pharmacophoric fragment in m-phenoxy-
benzaldehyde derivatives is C6H5OC6H4CH N which
includes the diphenyl ether moiety and CH N double
bond. Compounds possessing such a fragment could
exhibit pronounced fungicide activity. It should be
noted that a series of Schiff bases having an m-phen-
oxyphenyl group, were registered at the Russian
Research Center for Safety of Biologically Active
Substances. In addition, N-aryl-m-phenoxybenzyli-
deneamines can be used as polyfunctional components
of resin mixtures, as well as inhibitors of acid corro-
sion [7 10].
R = C6H5 (a), C6H5CO (b), 2,4-(O2N)2C6H3 (c).
The reaction of aldehyde I with aromatic hydra-
zines is selective, and hydrazones Va Vc are formed
in high yields (90 96%); the process can be regarded
as irreversible.
N-Aryl-m-phenoxybenzylideneamines IIIa IIIp
and arylhydrazones Va Vc are as a rule colored
viscous liquids or crystalline substances which were
purified by vacuum distillation or recrystallization.
Their structure was confirmed by the IR and 1H NMR
spectra and elemental analyses (see table).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 5 2001

SYNTHESIS AND REACTIONS OF SCHIFF BASES
679
EXPERIMENTAL
60 65 C, and the solvent was removed. The product
was recrystallized from ethanol. Yield 23 g (96%),
mp 158 160 C. Found, %: C 75.49; H 5.91; N 7.84.
C19H16N2O. Calculated, %: C 75.90; H 5.86; N 8.46.
Hydrazones Va and Vc were synthesized in
a similar way (see table).
The IR spectra were recorded on a Specord M82
instrument (NaCl or KBr prism) from samples pre-
pared as thin films (liquid products) or dispersions
1
in mineral oil (crystalline products). The H NMR
spectra were obtained on a Tesla BS-487 spectrometer
(100 MHz) relative to hexamethyldisiloxane as
internal reference; the solvents were CCl4, CDCl3,
and acetone-d6.
REFERENCES
1. Comprehensive Organic Chemistry, Barton, D. and
Ollis, W.D., Eds., Oxford: Pergamon, 1979, vol. 2.
N-Phenyl-m-phenoxybenzylideneamine (IIIa).
A four-necked reactor equipped with a stirrer, reflux
condenser, and thermometer was charged with 15 g
(0.076 mol) of m-phenoxybenzaldehyde (I), and
7.05 g (0.076 mol) of aniline was added under
vigorous stirring and cooling with water. The mixture
was then heated for 1.5 2 h at 100 110 C. It crystal-
lized on cooling. The product was recrystallized from
ethanol. Yield 88%, mp 58 60 C. Found, %: C 82.97;
H 5.73; N 5.80. C13H15NO. Calculated, %: C 83.50;
H 5.49; N 5.13.
2. Layer, R.W., Chem. Rev., 1963, vol. 63, pp. 487
492.
3. Ingold, C.K., Structure and Mechanism in Organic
Chemistry, Ithaca: Cornell Univ., 1969, 2nd ed.
4. Novopol’tseva, O.M., Cand. Sci. (Chem.) Disserta-
tion, Volgograd, 1995.
5. Kitaev, Yu.P. and Buzykin, B.I., Gidrazony (Hydra-
zones), Moscow: Nauka, 1974, pp. 10 15.
6. Popov, Yu.V., Korchagina, T.K., and Chicheri-
na, G.V., Russ. J. Org. Chem., 1996, vol. 32, no. 7,
pp. 1078 1079.
Compounds IIIb IIIp were synthesized following
a similar procedure (see table).
7. Russian Patent no. 2116999; Byull. Izobret., 1998,
no. 22.
N-Benzoyl-N -(m-phenoxybenzylidene)hydrazine
(Vb). A four-necked reactor equipped with a stirrer,
reflux condenser, and thermometer was charged with
15 g (0.076 mol) of m-phenoxybenzaldehyde and
50 ml of chloroform. Benzoylhydrazine, 10.3 g
(0.076 mol), was added under vigorous stirring and
cooling with water, the mixture was heated for 1 h at
8. Russian Patent no. 2117000; Byull. Izobret., 1998,
no. 22.
9. Russian Patent no. 2117001; Byull. Izobret., 1998,
no. 22.
10. Russian Patent no. 2115767; Byull. Izobret., 1998,
no. 20.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 5 2001