Synthesis of (E)-N-(3-alkoxy-4-acyloxyphenylmethylene)-N-(e-cyclohexyl) amines

Article abstract of DOI:10.1134/S1070363208060169

Previously unknown E isomers of azomethines (Schiff bases) were synthesized from vanillal and vanillin esters by their reaction with cyclohexylamine.

Full text of DOI:10.1134/S1070363208060169

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 6, pp. 1197–1199. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © E.A. Dikusar, N.G. Kozlov, V.I. Potkin, 2008, published in Zhurnal Obshchei Khimii, 2008, Vol. 78, No. 6, pp. 969–971.
Synthesis of (E)-N-(3-Alkoxy-4-acyloxyphenylmethylene)-
N-(e-cyclohexyl)amines
E. A. Dikusar, N. G. Kozlov, and V. I. Potkin
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus,
ul. Surganova 13, Minsk, 220072 Belarus
e-mail: evgen_58@mail.ru
Received December 18, 2007
Abstract—Previously unknown E isomers of azomethines (Schiff bases) were synthesized from vanillal and
vanillin esters by their reaction with cyclohexylamine.
DOI: 10.1134/S1070363208060169
Azomethines derived from natural aldehydophe-
nols, such as vanillin and vanillal, exhibit a high
biologic activity and reveal film-forming properties
and are thermo- and light-sensitive [1, 2].
HC=N
RO
The aim of this work was to obtain new azo-
methines on the basis of previously synthesized
vanillin and vanillal esters [3–6]. Condensation of the
vanillin and vanillal esters with cyclohexylamine in
absolute methanol (method a) gave corresponding (E)-
N-(3-alkoxy-4-acyloxyphenylmethylene)-N-(e-cyclo-
hexyl)amines I–XXIX containing ester and ether
OCR1
O
I−XXIX
R = Me, R1 = Et (I), Pr (II), Me2CH (III), Me(CH2)6 (IV),
Me(CH2)8 (V), Me(CH2)16 (VI), H2C=CMe (VII),
С6Н5СН2 (VIII), С6Н5С(Ме)НСН2 (IX), С6Н5 (X), 4-
ClC6H4 (XI), 2,4-Cl2C6H3 (XII), 4-BrC6H4 (XIII), 3-
O2NC6H4 (XIV), MeO (XV), EtO (XVI); R = Et, R1 = Me
(XVII), Et (XVIII), Pr (XIX), Me2CH (XX), Me2CHCH2
(XXI), Me(CH2)8 (XXII), Me(CH2)11 (XXIII), Me(CH2)16
(XXIV), Z-С6H5C(H)=C(C≡N) (XXV), 4-MeC6H4
(XXVI), 3,5-(O2N)2C6H3 (XXVII), MeO (XXVIII), EtO
(XXIX).
1
groups (yield 83–93%). According to H NMR data,
the purity of the compounds was 97 1%.
Liquid and low-melting vanillin and vanillal esters
also readily react with cyclohexylamine without a
solvent. By simply mixing stoichiometric amounts of
corresponding aldehyde and cyclohexylamine and
subsequently carefully heating the resulting mixture at
60–80°C (method b) we obtained azomethines I–IX,
XV–XXIV, XXVIII, and XXIX in quantitative (99
1%) yields. The purity of the products was 92 2%.
770), C–HAlk (2980–2800), C=O (1770–1730), C=N
(1647–1641), C–Carom (1600–1350), and C–O (1300–
Compounds I–XXIX are colorless or slightly
colored crystalline compounds with well-defined
melting points. The azomethines do not need
additional purification and contain no admixtures of
the starting compounds. The structure of azomethines
I–XXIX was established by the elemental analyses and
cryoscopic molecular weights (see table), as well as
IR, UV, and 1H NMR spectra.
1000) bonds. The presence
of NO2 groups in
compounds XIV, XXVII is confirmed by characteristic
bands at 1540–1525 and 1349–1345 cm–1. The C≡N
group in compound XXV absorbs at 2225 cm–1.
The UV spectra of compounds I–XXIX contain the
following absorption bands [λmax, nm (ε 10–3)]: 209
(13), 220 (13), 253 (9), 300 (4). They are characteristic
of the (E)-N-(3-alkoxy-4-acyloxyphenylmethylene)-N-
(e-cyclohexyl)amine chromophore.
The IR spectra of azomethines I–XXIX show
absorption bands (ν, cm–1) of C–HAr (3100–3000, 890–
1197

1198
DIKUSAR et al.
Yields, melting points, elemental analyses, and molecular weights of azomethines I–XXIX
Found, %
H
Calculated, %
М
Comp.
no.
Yield,
%
mp,
°С
Formula
C
N
C
H
N
found
calculated
87
88
84
83
89
90
83
93
52–53
44–45
51–52
32–33
36–37
65–66
44–45
33–34
70.74
71.57
71.49
73.72
74.50
77.08
71.94
75.35
8.22
8.43
8.38
9.37
9.86
10.89
7.80
7.28
4.30
4.41
4.37
3.65
3.48
2.54
4.33
3.81
C17H23NO3
C18H25NO3
C18H25NO3
C22H33NO3
C24H37NO3
C32H53NO3
C18H23NO3
C22H25NO3
70.56
71.26
71.26
73.50
74.38
76.90
71.73
75.19
8.01
8.31
8.31
9.25
9.62
10.69
7.69
7.17
4.48
4.62
4.62
3.90
3.61
2.80
4.65
3.99
281.3
290.5
292.7
348.0
377.1
481.8
290.2
337.4
289.4
303.4
303.4
359.5
387.6
499.8
301.4
351.4
I
II
III
IV
V
VI
VII
VIII
90
92
93
27–28
84–85
76.19
74.92
7.83
6.94
6.04
3.52
3.92
3.50
C24H29NO3
C21H23NO3
C21H22ClNO3
75.96
74.75
67.83
7.70
6.87
5.96
3.69
4.15
3.77
364.0
321.6
358.5
379.5
339.4
371.9
IX
X
XIa
117–118 68.02
96–97 62.31
127–128 60.78
XIIb
XIIIc
XIV
XV
89
93
90
85
5.37
5.40
5.82
7.37
3.19
2.97
7.04
4.58
C21H21Cl2NO3
C21H22BrNO3
C21H22N2O5
C16H21NO4
62.08
60.59
65.96
65.96
5.21
5.33
5.80
7.26
3.45
3.36
7.33
4.81
390.9
404.4
362.7
282.3
406.3
416.3
382.4
291.3
73–74
27–28
66.14
66.25
86
88
55–56
47–48
67.02
70.68
7.69
8.12
4.23
4.22
C17H23NO4
C17H23NO3
66.86
70.56
7.59
8.01
4.59
4.48
297.1
282.0
305.4
289.4
XVI
XVII
90
91
92
61–62
42–43
53–54
71.66
72.04
72.06
8.45
8.59
8.64
4.47
4.14
4.20
C18H25NO3
C19H27NO3
C19H27NO3
71.26
71.89
71.89
8.31
8.57
8.57
4.62
4.41
4.41
292.2
308.3
305.8
303.4
317.4
317.4
XVIII
XIX
XX
93
90
88
85
93
93
90
42–43
46–47
47–48
30–31
48–49
72.73
75.05
75.91
77.34
74.83
8.96
9.93
4.01
3.08
2.87
2.50
6.42
3.55
9.18
C20H29NO3
C25H39NO3
C28H45NO3
C33H55NO3
C25H26N2O3
C23H27NO3
C22H23N3O7
72.47
74.77
75.80
77.14
74.60
75.59
59.86
8.82
9.79
4.23
3.49
3.16
2.73
6.96
3.83
9.52
321.8
387.2
429.7
492.6
388.4
354.9
421.0
331.5
401.6
443.7
513.8
402.5
365.5
441.4
XXI
XXII
XXIII
XXIV
XXV
10.29
10.93
6.55
10.22
10.79
6.51
108–109 75.72
7.54
7.45
XXVI
XXVII
92–93
32–33
24–25
60.03
66.99
67.94
5.32
5.25
86
88
7.75
8.03
4.46
4.10
C17H23NO4
C18H25NO4
66.86
67.69
7.59
7.89
4.59
4.39
292.5
308.7
305.4
319.4
XXVIII
XXIX
a Found Cl, %: 9.28, calculated Cl, %: 9.53. b Found Cl, %: 17.11, calculated Cl, %: 17.45. c Found Br, %: 18.89, calculated Br, %: 19.19
The 1H NMR spectra of azomethines I–XVI
7.00–7.50 ppm. The HC=N proton signals are singlets
at 8.20–8.30 ppm, what is characteristic of E isomers
[1–9].
display signals of the methoxy group as singlets at
1
3.85–3.92 ppm. The ethoxy protons in the H NMR
spectra of compounds XVII–XXIX give a triplet at
1.40–1.70 ppm (Me) and a quartet at 4.00–4.50 ppm
(CH2O). The cyclohexyl protons (C6H11) appear as a
multiplet at 1.10–2.10 ppm. The aromatic proton
(C6H3) signals of azomethines I–XXIX resonate at
1
The IR, UV, and H NMR spectra of azomethines
I–XXIX contain absorption bands and proton signals
confirming the presence of corresponding structural
fragments of ester groups [1–9].
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 6 2008

SYNTHESIS OF (E)-N-(3-ALKOXY-4-ACYLOXYPHENYLMETHYLENE)-...
1199
To confirm the E configuration assigned to the
synthesized azomethines, we performed quantum-
chemical calculations of heats of formation (Hf) for the
E and Z isomers of azomethines I, VIII, XVII, and
XXVI (equatorial conformations). The calculations
were made by the semiempirical MNDO PM3 method
with full geometry optimization, using the GAMESS
program [10]. The following Hf values (kcal mol–1)
were obtained for the E and Z (in brackets) isomers: I
–101.3 (–100.5); VIII –67.7 (–66.8); XVII –102.9
(–102.5); XXVI –76.7 (–75.9). According to the
quantum-chemical results, the E configuration is 0.4–
0.9 kcal mol–1 more favored by energy than Z, which
agrees well with data for related compounds [7–9].
cycloxexylamine in 30 ml of absolute methanol was
refluxed for 15 min and then filtered while hot through
a folded paper filter, cooled, and left for 10–15 h at 5°C.
Crystals of compounds I–XXIX formed and were
filtered off on a glass frit, washed with a little
methanol, and dried in air (see table).
(E)-N-(3-Alkoxy-4-acyloxyphenylmethylene)-N-
(e-cyclohexyl)amines I–IX, XV–XXIV, XXVIII, and
XXIX. Method b. A mixture of 5 mmol of vanillin or
vanillal ester and 5 mmol of cyclohexylamine was
carefully heated at 60–80°C for 10–15 min in a
ceramic crucible. The homogeneous melt that formed
crystallized after cooling, and the product was dried in
air.
Heats of formation were also calculated for the
equatorial and axial conformers of the more stable E
isomers of azomethines I, VIII, XVII, and XXVI. The
following values (kcal mol–1) were obtained (values in
brackets relate to the axial conformers): I –101.3
(–100.9); VIII –67.7 (–66.5); XVII –102.9 (–100.9);
XXVI –76.7 (–75.2). These results show that the
equatorial conformation is 0.4–2.2 kcal mol–1 more
favored by energy than the axial one. Hence, quantum-
chemical calculations gave evidence for our
assignment to azometines I–XXIX of the (E)-N-(3-
alkoxy-4-acyloxyphenylmethylene)-N-(e-cyclohexyl)-
amine structure.
REFERENCES
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1
nol. The H NMR spectra were taken on a Tesla BS-
587A (100 MHz) spectrometer for 5% CDCl3 solutions
against TMS. The elemental analyses were obtained on
an Elementar Vario EL-II C,H,N,O,S-analyzer
(uncertainty 0.1%). The molecular weights were
determined cryoscopically in benzene.
Vanillin and vanillal esters were synthesized
according to [3–6].
(E)-N-(3-Alkoxy-4-acyloxyphenylmethylene)-N-
(e-cyclohexyl)amines I–XXIX. Method a. A solution
of 5 mmol of vanillin or vanillal ester and 5 mmol of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 6 2008