Synthesis of E-3-alkoxy-4-hydroxy(alkoxy, acyloxy)-phenylmethylene(2- hydroxyphenyl)amines

Article abstract of DOI:10.1134/S1070363208080173

By the reaction of vanillin and vanillal derivatives with 2-aminophenol previously unknown E isomers of azomethines (Schiff bases) containing hydroxy, ether, and ester groups were synthesized.

Full text of DOI:10.1134/S1070363208080173

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 8, pp. 1569–1572. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © E.A. Dikusar, V.I. Potkin, N.G. Kozlov, 2008, published in Zhurnal Obshchei Khimii, 2008, Vol. 78, No. 8, pp. 1334–1337.
Synthesis of E-3-Alkoxy-4-hydroxy(alkoxy, acyloxy)-
phenylmethylene(2-hydroxyphenyl)amines
E. A. Dikusar, V. I. Potkin, and N. G. Kozlov
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus,
ul. Surganova 13, Minsk, 220072 Belarus
e-mail: evgen_58@mail.ru
Received March 3, 2008
Abstract—By the reaction of vanillin and vanillal derivatives with 2-aminophenol previously unknown E
isomers of azomethines (Schiff bases) containing hydroxy, ether, and ester groups were synthesized.
DOI: 10.1134/S1070363208080173
We have reported recently on the synthesis and
investigation of the film-forming, thermo-, and
photosensitive properties of aromatic azomethines of
the vanillin series [1–3]. These compounds turned out
to be promising objects for preparing nanofilms and
nanomaterials [4–6].
methanol under reflux. We have prepared aromatic
azomethines (Schiff bases) IIIa–IIIs, IVa–IVm in
preparative yields 86–91%. The reaction com-pleted in
10–15 min. It proceeded under mild condi-tions in the
absence of catalyst favorable for the preservation of
the labile ether groups. Purity of the compounds
1
obtained according to H NMR data was 97 1%.
The aim of the work presented is the development
of the procedure for preparing new aromatic azo-
methines containing hydroxy, ether, and ester groups
by condensation of vanillin and vanillal and their
ethers and esters I with 2-aminophenol II in anhydrous
Liquid and low-melting aldehydes of the vanillin series
I easily react with 2-aminophenol II also without a
solvent. By simple mixing of stoichio-chemical
amounts of compounds I and II followed by careful
heating of the mixture obtained to 60–80°C
OH
R1O
NH
H
OR
C
CHO
NH2
OH
+
RO
RO
O
N H
R1O
R1O
V
I
II
IIIа–IIIs, IVа–IVl
III, R = Me, R1 = H (a), Me (b), EtС(O) (c), PrС(O) (d), Me2CHС(O) (e), Me(CH2)6С(O) (f), Me(CH2)8С(O) (g),
Me(CH2)16С(O) (Bh), H2C=CMeС(O) (i), С6Н5СН2С(O) (j), С6Н5С(Ме)НСН2С(O) (k), С6Н5С(O) (l), 4-ClC6H4С(O) (m),
2,4-Cl2C6H3С(O) (n), 2,4-Cl2C6H3ОСН2С(O) (o), 4-BrC6H4С(О) (p), 3-O2NC6H4С(О) (q), MeOС(О) (r), EtOС(О) (s);
IV, R = Et, R1 = Н (a), Me (b), МеС(О) (c), EtС(О) (d), PrС(О) (e), Me2CHС(О) (f), Me2CHCH2С(О) (g), Me(CH2)11С(О)
(h), 4-MeC6H4С(О) (i), 3,5-(O2N)2C6H3С(О) (j), MeOС(О) (k), EtOС(О) (l).
1569

1570
DIKUSAR et al.
azomethines IIIa–IIIl, IIIr, IIIs; IVa–IVi, IVk, IVl
were prepared in the quantitative yield and the 92 2%
purity quite sufficient for preparing azomethine
nanofilms by means of thermovacuum deposition [1–
6]. During this process additional purification occurs to
the title substance content no less than 99%. Note that
introduction of a hydroxy group in the azomethine
molecule significantly increases the adhesion of
nanofilms to the surface of the polar sublayers (glass,
quartz, sitall).
azomethines, but compounds of higher purity are
obtained. Performing the reaction without a solvent
leads to increase in the yield and significantly
simplifies the process of isolation.
The compounds obtained IIIa–IIIs , IVa–IVl are
colorless or slightly colored crystalline substances
having a clear melting point. Azomethines do not need
any additional purification and contain no admixtures
of starting compounds. The structure of azomethines
IIIa–IIIs, IVa–IVl was established by means of the
elemental analysis, the cryoscopic evaluation of
molecular weight (see the table), IR, UV, and 1H NMR
Hence, performing the reaction in methanol leads to
the insignificant decrease in the yield of the target
Yields, melting points, elemental analysis data, and the molecular weight of azomethines IIIa–IIIs ,IVa–IVl
Found, %
H
Calculated, %
H
М
Comp.
no.
Yield,
%
mp,
°С
Formula
C
N
C
N
found
calculated
87
89
86
87
89
88
90
86
90
89
88
91
90
91
87
91
90
86
88
87
89
90
28–29
47–48
51–52
61–62
66–67
28–29
25–26
42–43
83–84
32–33
67–68
79.45
70.32
68.46
69.37
69.41
71.88
72.69
75.72
69.64
73.40
74.21
5.53
5.97
5.85
6.13
6.24
7.50
7.93
9.35
5.62
5.45
5.97
4.90
4.32
3.69
3.95
3.82
4.15
5.21
5.48
5.96
6.49
5.86
5.44
5.19
4.60
4.14
4.09
3.45
3.32
2.51
4.18
3.58
3.37
3.65
3.46
3.02
2.87
2.89
6.94
4.26
4.20
5.12
4.80
4.23
C14H13NO3
C15H15NO3
C17H17NO4
C18H19NO4
C18H19NO4
C22H27NO4
C24H31NO4
C32H47NO4
C18H17NO4
C22H19NO4
C24H23NO4
C21H17NO4
C21H16ClNO4
C21H15Cl2NO4
C22H17Cl2NO5
C21H16BrNO4
C21H16N2O6
C16H15NO5
C17H17NO5
C15H15NO3
C16H17NO3
C17H17NO4
69.12
70.02
68.22
69.00
69.00
71.52
72.52
75.40
69.44
73.12
74.02
72.61
66.06
60.59
59.21
59.17
64.29
63.78
64.75
70.02
70.83
68.22
5.39
5.88
5.72
6.11
6.11
7.37
7.86
9.29
5.50
5.30
5.95
4.93
4.22
3.63
3.84
3.87
4.11
5.02
5.43
5.88
6.32
5.72
5.76
5.44
4.68
4.47
4.47
3.79
3.52
2.75
4.50
3.88
3.60
4.03
3.68
3.36
3.14
3.29
7.14
4.65
4.44
5.44
5.16
4.68
231.7
250.1
291.0
303.6
305.8
358.2
386.3
483.4
301.3
352.5
380.3
328.4
367.7
404.5
431.9
410.4
380.0
291.2
307.8
250.3
264.1
291.0
243.3
257.3
299.3
313.4
313.4
369.5
397.5
509.7
311.3
361.4
389.5
347.4
381.8
416.3
446.3
426.3
392.3
301.3
315.3
257.3
271.3
299.3
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
IIIj
IIIk
IIIl
127–128 72.95
155–156 66.24
121–122 60.87
162–163 59.58
162–163 59.45
151–152 64.51
IIIma
IIInb
IIIoc
IIIpd
IIIq
IIIr
IIIs
IVa
IVb
IVc
64–65
43–44
30–31
64.02
64.99
70.28
117–118 71.03
24–25 68.34
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 8 2008

SYNTHESIS OF E-3-ALKOXY-4-HYDROXY(ALKOXY, ACYLOXY)-...
1571
Table (Contd.)
Found, %
Calculated, %
М
Comp.
no.
Yield,
mp,
Formula
%
°С
C
H
N
C
H
N
found
302.2
calculated
89
76–77
69.29
6.14
4.09
C18H19NO4
69.00
6.11
4.47
313.4
IVd
88
86
86
87
91
90
86
86
32–33
56–57
65–66
30–31
97–98
69.88
70.01
70.52
74.28
73.92
6.63
6.59
6.88
8.84
5.64
3.88
5.49
5.93
3.95
3.98
3.75
2.76
3.51
8.98
4.20
4.04
C19H21NO4
C19H21NO4
C20H23NO4
C28H39NO4
C23H21NO4
C22H17N3O8
C17H17NO5
C18H19NO5
69.71
69.71
70.36
74.14
73.58
58.54
64.75
65.64
6.47
6.47
6.79
8.67
5.64
3.80
5.43
5.81
4.28
4.28
4.10
3.09
3.73
9.31
4.44
4.25
319.7
317.6
326.8
439.7
366.2
436.6
307.9
320.1
327.4
327.4
341.4
453.6
375.4
451.4
315.3
329.4
IVe
IVf
IVg
IVh
IVi
IVj
IVk
IVl
221–222 58.83
46–47
47–48
64.90
65.72
a Found Cl, %: 8.83. Calculated Cl, %: 9.29. b Found Cl, %: 16.81. Calculated Cl, %: 17.03. c Found Cl, %: 15.58. Calculated Cl, %: 15.89.
d Found Br, %: 18.46. Calculated Br, %: 18.75.
spectra. In the IR spectra of azomethines IIIa–IIIs,
IVa–IVl the absorption bands of OH bonds are ob-
served at 3450–3380 cm–1; C-HAr at 3100–3000, 780–
680 cm–1; C–HAlk at 2990–2840 cm–1; C=O at 1770–
1740 cm–1; C=N at 1630–1625 cm–1; C–Carom at 1600–
1380 cm–1; C–O at 1285–1035 cm–1. In the IR spectra
of the compounds IIIq and IVj the presence of NO2
groups is confirmed by the characteristic absorption
bands at 1541–1525 and 1349–1343 cm–1 .
In the IR, UV, and 1H NMR spectra of azomethines
IIIa–IIIs, IVa–IVl the absorption bands and the
signals of protons prove the presence of the cor-
responding structural fragments of the ester groups.
Hence, the reaction of aldehydes of the vanillin
series I with 2-aminophenol II proceeds with the
formation of azomethines IIIa–IIIs, IVa–IVl and
does not lead to 2,3-dihydrobenzoxazoles V. All the
attempts to prepare compounds V in this mode failed
in contrast to the ready synthesis of 2,3-dihydro-1H-
benzimidazoles by the reaction of aldehydes of the
vanillal series I with o-phenylenediamine [8].
In the UV spectra of compounds IIIa–IIIs, IVa–
IVl the following absorption bands are observed [λmax
,
nm (ε)]: 204 (34000), 232 (14000), 282 (10000), 343
(10000). They are caused by the E-3-alkoxy-4-hydroxy
(alkoxy, acyloxy)phenylmethylene(2-hydroxyphenyl)
To confirm the E configuration ascribed to the
azomethines synthesized the quantum-chemical cal-
culations of the heats of formation (Hf) of E and Z
isomers of azomethines IIIc, IIIl; IVd and the
isomeric dihydrobenzoxazoles V were carried out. The
quantum-chemical calculations were performed within
the framework of the semiempirical MNDO PM3
approximation by means of the GAMESS program [9].
A complete optimization of all interatomic distances,
and of the bond and dihedral angles was carried out.
The Hf values (kcal mol–1) of E isomers, of Z isomers
(in parentheses), and of the corresponding
dihydrobenzoxazoles (in brackets) are as follows: IIIc:
–93.8 (–92.7) [–97.3]; IIIl: –55.0 (–54.8) [–57.9]; IVd:
–101.4 (–102.2) [–103.6].
1
amine fragments. In the H NMR spectra of azo-
methines IIIa–IIIs, IVb the signals of the MeO
protons are observed as singlets at δ 3.85–3.92 ppm.
1
The signals of EtO group in H NMR spectra of com-
pounds IVa–IVl appeared as triplets at 1.40–1.70 ppm
(Me) and quartets at 4.00–4.50 ppm (CH2). The signals
of OH groups give rise to broadened singlets at 4.95–
5.65 ppm. The signals of the aromatic protons of
azomethines IIIa–IIIs, IVa–IVl are located in the
range 6.60–7.70 ppm, the proton of azomethine group
(HC=N) gives a singlet at 8.55–8.65 ppm characteristic
of E isomers of azomethines. Chemical shift of this
proton in Z isomer is usually located about 0.5 ppm
downfield due to its position in the deshielding area of
the benzene ring of 2-hydroxyphenylamine fragment
of the molecule [7].
The quantum-chemical calculations showed that E
configuration is by 0.2–1.1 kcal mol–1 energetically
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 8 2008

1572
DIKUSAR et al.
2. Dikusar, E.A., Kozlov, N.G., Potkin, V.I., Azarko, V.A.,
and Yuvchenko, A.P., Zh. Obshch. Khim., 2007, vol. 77,
no. 10, p. 1700.
more favorable than Z configuration. At the same time
2,3-dihydrobenzoxazoles V are 2.2–3.5 kcal mol–1
thermodynamically more favorable than E-azo-
methines IIIa–IIIs; IVa–IVl, but they do not form
under these reaction conditions.
3. Dikusar, E.A., Kozlov, N.G., Potkin, V.I., Azarko, V.A.,
and Yuvchenko, A.P., Zh. Obshch. Khim., 2008, vol. 78,
no. 2, p. 303.
EXPERIMENTAL
4. Dikusar, E.A., Kozlov, N.G., Tlegenov, R.T., and Ute-
niyazov, K.U., Azometiny na osnove vanilina i vanilalya
(The Vanillin- and Vanillal-based Azomethines),
Karakalpakstan, Nukus, 2007.
IR spectra were recorded on a Nicolet Protege-460
IR Fourier spectrometer in KBr. UV spectra were
measured on a Varian Cary-300 UV-Vis spec-
5. Azarko, V.A., Dikusar, E.A., and Yuvchenko, A.P.,
trophotometer from the 10–4 M methanol solutions. H
1
Abstracts of
Papers, Mezhdunarodnaya nauchno-
NMR spectra were taken on a Tesla BS-587A
spectrometer (100 MHz) from 5% CDCl3 solutions
against internal TMS. The elemental analyses were
carried out on an Elementar Vario EL-III C,H,N,O,S-
analyzer, the evaluation accuracy 0.1%. Molecular
weight (M) was measured cryoscopically in benzene.
tekhnicheskayz konferentsiya “Polymernye kompozity i
tribologiya” (Intern. Scien. and Techn. Conf.
“Polymeric Composites and Tribology”), Polikomtrib-
2007, Belarus, Gomel’, July 16–19, 2007, Gomel’,
2007, p. 102.
6. Azarko, V.A., Dikusar, E.A., Potkin, V.I., Kozlov, N.G.,
and Yuvchenko, A.P., in Optika neodnorodnykh
struktur-2007, materialy mezhdunarodnoi nauchno-
prakticheskoi konferentsii (Optics of the Nonhomogenic
Structures-2007, Transactions of the International
Scientific and Practical Conference), October 2–3,
2007, Mogilev, Belarus: Kuleshov MGU, 2007, p.27.
The vanillin and vanillal esters were obtained
according to the procedures [10–13].
E-3-Alkoxy-4-hydroxy(alkoxy, acyloxy)phenyl-
methylen(2-hydroxyphenyl)amines (IIIa–IIIs; IVa–
IVl). method A. A solution of 5 mmol of the vanillin or
vanillal ester I and 5 mmol of 2-aminophenol II in 30
ml of anhydrous methanol was boiled for 15 min, and
the hot solution was filtered through the folder paper
filter, cooled, and left standing for 10–15 h at 5°C. The
crystals of compounds IIIa–IIIs, IVa–IVl were
filtered off on a glass frit, washed with small amount
of methanol, and dried in air (see the table).
7. Dyer, J.R., Applications of Absorption Spectroscopy of
Organic Compounds, New York: Prenice Hall, 1965.
8. Dikusar, E.A., Kozlov, N.G., and Potkin, V.I., Zh.
Obshch. Khim., 2007, vol. 77, no. 11, p. 1871.
9. Schmidt, M.W., Baldridge, K.K., Boatz, J.A., Elbert, S.T.,
Gordon, M.S., Jensen, J.H., Koseki, S., Matsunaga, N.,
Nguyen, K.A., Su, S.J., Midus, T.L., Dupnis, M., and
Montgomery, J.A., J. Comput. Chem., 1993, vol. 14, no. 7,
p. 1347.
E-3-Alkoxy-4-hydroxy(alkoxy, acyloxy) phenyl-
methylene(2-hydroxyphenyl)amines (IIIa–IIIl, IIIr,
IIIs; IVa–IVi, IVk, IVl). method B. A mixture of
5 mmol of vanillin or vanillal ester I and 5 mmol of 2-
aminophenol were heated carefully at 60–80°C for 10–
15 min in a ceramic crucible. The homogenic melt
solidified after cooling, and the product was dried in air.
10. Dikusar, E.A., Vyglazov, O.G., Moiseichuk, K.L., Zhu-
kovskaya, N.A., and Kozlov, N.G., Zh. Prikl. Khim.,
2005, vol. 78, no. 1, p. 122.
11. Dikusar, E.A. and Kozlov, N.G., Khim. Prirodn. Soed.,
2005, no. 1, p. 74.
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1. Dikusar, E.A., Kozlov, N.G., Potkin, V.I., Azarko, V.A.,
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no. 2, p. 306.
13. Dikusar, E.A., Zh. Prikl. Khim., 2006, vol. 79, no. 6,
p. 1043.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 8 2008