Synthesis and study of the structure of the reaction products formed from cyclopenta[c]quinolinium quarternary salts and p-dimethylaminobenzaldehyde

Article abstract of DOI:10.1134/S1070363209110206

The presence of active methylene group in the molecules of cyclopenta[c]quinolinium quarternary salts permitted to obtain products of their reaction with p-dimethylaminobenzaldehyde. Structures of the reaction products were established from ¹H

Full text of DOI:10.1134/S1070363209110206

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 11, pp. 2406–2411. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © M.V. Mel’nik, O.V. Bondarchuk, A.V. Turov, D.O. Mel’nik, N.I. Ganushchak, 2009, published in Zhurnal Obshchei Khimii, 2009,
Vol. 79, No. 11, pp. 1884–1889.
Synthesis and Study of the Structure
of the Reaction Products Formed
from Cyclopenta[c]quinolinium Quarternary Salts
and p-Dimethylaminobenzaldehyde
M. V. Mel’nika, O. V. Bondarchuka, A. V. Turovb,
D. O. Mel’nikc, and N. I. Ganushchakd†
a Ivano-Frankovsk State Medical University, ul. Galitskaya 3, Ivano-Frankovsk, 76000 Ukraine
e-mail: melnyk_dm@list.ru
b Kiev National University, Kiev, Ukraine
c Ivano-Frankovsk National Technical University of Gas and Oil, Ivano-Frankovsk, Ukraine
d Lviv National University, Lviv, Ukraine
Received January 22, 2009
Abstract—The presence of active methylene group in the molecules of cyclopenta[c]quinolinium quarternary
salts permitted to obtain products of their reaction with p-dimethylaminobenzaldehyde. Structures of the
reaction products were established from 1H and 13C NMR spectral data using the correlation spectra. The effect
of substituents at nitrogen on the visible absorption spectra was studied. The investigation of formation of the
frontier orbitals in the reaction products by quantum chemical calculations revealed the reason of the coloration
of the dyes synthesized.
DOI: 10.1134/S1070363209110206
2
1
The presence of saturated five- and six-membered
cycles along with the pyridine fragment in the structure
of heterocyclic compounds is a real sign of their
biological activity [1]. Studies of the effect of various
substituents on different types of activity requires a
broad set of compound containing versatile substituents
in the pharmacophore fragments of molecules.
R1
9
6
9b
3
9а
5а
8
3а
7
4
+
N5
R
The presence in the structures under investigation
of the negative charge and an exess electronic density
in the position 1 of the compounds obtained makes
them interesting nucleophilic reagents which may enter
in the reactions of nucleophilic substitution at the
carbonyl group of aromatic aldehydes. The substituents
at the nitrogen do not affect significantly the charge of
the methylene group located in the γ-position of the
pyridinium cycle.
Recent studies permitted the establishment of the
conditions of the reaction between secondary aromatic
amines, formaldehyde, and cyclopentanone in the
butanol-1-nitrobenzene mixture acidified with perchloric
acid leading to the easy one-pot formation of the cyclo-
penta[c]quinolinium quarternary salts [2].
With the purpose of establishing the reactivity of
the obtained quarternary cyclopenta[c]quinolinium
salts we performed the quantum chemical calculations
of charges and electronic density distribution on the
carbon atoms [3] by PM3 method, the most suitable
among the semiempiric procedures (Table 1).
The reaction of the corresponding cyclopenta[c]-
quinolinium salts I–VI with equimolar amount of p-
dimethylaminobenzaldehyde in boiling acetic anhyd-
ride leads to the formation of colored compounds VII-
XII according to the following scheme.
†
Deceased.
2406

SYNTHESIS AND STUDY OF THE STRUCTURE OF THE REACTION PRODUCTS
H3C
CH3
2407
N
1
R
O
H
CH3
CH3
+
HC
C
N
+
N
ClO4−
1
R
R
I−VI
A
ClO4−
+
N
R
VII−XII
H3C
N
CH3
1
R
C
H
+
B
N
ClO4−
R
R1 = H, R = CH3 (I), (A) (VII), R = C2H5, R1 = H (II), (A) (VIII), R = CH2C6H5, R1 = H (III), (A) (IX), R = C6H5, R1 = H
(IV), (A) (X), R = C6H5, R1 = 8,9-(CH=CH)2 (V), (A) (XI), R = 5,6-(CH2)3, R1 = H (VІ), (A) (XII).
The reaction mixture was treated with diethyl ether
and the product was crystallized from ethanol. The
characteristics of the compounds obtained, their visible
absorption spectra, and H NMR spectra are presented
in Table 2.
heteronuclear 1H–13C HMQC and HMBC correlations.
The interesting specific feature of the 1H NMR
spectrum of the dye obtained is the extreme downfield
location of one of doublets of the aromatic protons
(9.52 ppm). Attribution of this signal as well as of the
others belonging to the aromatic protons follows from
the COSY spectrum (Fig. 1).
1
Evidently formula A is more probable because the
methylene group located in the γ-position to the
pyridinium nitrogen atom must be more active, still the
formation of the structure B cannot be rejected. For
establishing the structure of the dye synthesized we
A doublet at 9.52 ppm is the spin–spin coupling
partner for the triplet at 7.67 ppm. Therefore the
downfield doublet must be attributed to the H5 proton
of the benzoquinoline fragment. Most probably the
downfield location of the signal is connected with the
1
13
recorded its H and C NMR spectra and carried out
the experiments of homonuclear (COSY, NOESY) and
Table 1. Atomic charges and HOMO π-electronic density calculated by PM3 method for N-substituted cyclopenta[c]-
quinolines
Atomic charges
HOMO π-electronic density
R
R1
N
C9b
C1
C4
C3
N
C9b
C1
C4
C3
CH3
H
Н
Н
Н
0.465
0.448
0.456
0.592
0.589
0.072
0.072
0.071
0.058
0.038
–0.075 –0.121
–0.075 –0.125
–0.075 –0.129
–0.071 –0.118
–0.045
–0.044
–0.045
–0.044
–0.049
0.365
0.362
0.006
0.351
0.245
0.316
0.315
0.003
0.311
0.086
0.121
0.120
0.001
0.102
0.046
0.384
0.386
0.001
0.329
0.254
0.150
0.149
0.000
0.109
0.072
С2Н5
СН2–С6Н5
С6Н5
С6Н5
(СН=СН)2
–0.078
–0.096
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 11 2009

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MEL’NIK et al.
Table 2. Characteristics of 1-(p-dimethylaminobenzylidene) cyclopenta[c]quinolinium derivatives
Yield, Found N,
Calculated λmax, nm
Comp.
no.
R
R1
mp
Formula
1Н MR spectrum, δ, ppm
%
%
N, %
(log ε)
CH3
H
232
79
6.67
C22H23ClN2O4
6.75
559
6.79 (2Н, Ph), 7.50–7.52 (2Н, Ph),
VII
(3.36) 7.8 (3Н, Ph), 8.62 (1Н, Ph), 8.92
(1Н, 4-СН), 7.82 (1Н, С=С), 2.50
(2Н, 2-СН2), 2.80(3Н, N-CH3), 3.08
[6H, N(CH3], 3.34 (2H, 3-CH2)
С2Н5
Н
141
60
6.55
C23H25ClN2O4
6.53
565
6.75 (2Н, Ph), 6.93–7.43 (2Н, Ph),
VIII
(3.40) 8.47–8.57 (2Н, Ph), 9.20 (1Н, 4-
СН), 7.90 (1Н, С=С), 2.50 (2Н, 2-
СН2), 2.85 (2Н, 3-СН2), 5,0 (2H,
N-CH2), 1,7 (3H, CH3, 5-Et), 3,10
(6H, N(CH3)2)
СН2-С6Н5
Н
244–
246
95
93
95
86
5.68
5.75
5.35
6.29
C28H27ClN2O4
C27H25ClN2O4
C31H27ClN2O4
С24Н26ClN2O
5.71
5.87
5.32
6.35
560
6.80 (2Н, Ph), 7.32 (5H, Ph) 7.60
IX
Х
(3.50) (2Н, Ph), 8.34–8.8 (2Н, Ph), 9.45
(1Н, 4-СН), 7.90 (1Н, С=С), 2.50
(2Н, 2-СН2), 3.13 (2Н, 3-СН2), 3.09
[6H, N(CH3)2], 4.15 (2H, CH2-Ph)
С6Н5
Н
272
583
6.80 (2Н, Ph), 7.55 (5H, Ph), 7.62
(3.56) (2Н, Ph), 7.80 (2Н, Ph), 8.00 (2Н,
Ph), 9.16(1Н, 4-СН), 7.73 (1Н,
С=С), 2.50 (2Н, 2-СН2), 3.45 (2Н,
3-СН2), 3.10 [6H, N(CH3)2]
С6Н5
8,9-
162–
163
582
6.81 (2Н, Ph), 7.81 d (5H, Ph), 7.41
ХI
ХII
(CH=CH)2
(3.74) (2Н, Ph), 7.67–8.17 (3Н, Ph), 8.34
(2Н, Ph), 9.52 (1H, Ph), 9.10 (1Н,
4-СН), 7.81 (1Н, С=С), 3.42 (4Н,
2,3-СН2), 3.03 [6H, N(CH3)2]
5,6-(CH2)3
H
128–
130
554
6,78 (2Н, Ph), 7,55 (2Н, Ph), 7,88
(3.27) (2Н, Ph), 8,69 (1Н, Ph), 9,09(1Н, 4-
СН), 7,84 (1Н, С=С), 2,50 (2Н, 2-
СН2), 3,32 (4Н, 2,3-СН2), 4.82 (2H,
CH2), 2.33 (2H, CH3), 3.13 (2H,
CH3), 3.08 [6H, N(CH3)2]
spatial proximity to the exocyclic double bond of this
compound. In the 13C NMR spectrum of product XI
the number of signals corresponds to the assumed
formula of the compound. The attribution of signals
can be made on the basis of correlations observed in
the two-dimentional HMQC and HMBC spectra.
Coordinates of cross-peaks found in these spectra are
presented in Table 3.
that for some signals these correlations were not found
because of the small intensity of the corresponding
cross-peaks. In this case the attribution was carried out
on the basis of the assembly of correlations through 2–
3 chemical bonds observed in HMBS spectra similarly
to the nonprotonated carbon atoms. Most important
HMBC correlations forming the basis for attribution of
signals are shown by arrows.
The attribution of signals of the protonated carbon
atoms follows from the heteronuclear correlations
through one chemical bond in HMQC spectrum. Note
On the basis of structural formula of compound XI
the presence of significant spatial hindrances in the
molecule may be suggested. But it is not the case. The
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 11 2009

SYNTHESIS AND STUDY OF THE STRUCTURE OF THE REACTION PRODUCTS
7.81
2409
7.41
9.10
6.81
7.67
7.33
8.34 8.17
9.52
F2,
ppm
7.0
7.5
8.0
8.5
9.0
9.5
9.6
9.2
8.8
8.4
8.0
7.6
7.2
6.8 F1, ppm
Fig. 1. COSY spectrum of compound XI.
Table 3. Cross-peak coordinates in the HMQC and HMBC spectra found for product XI
13С measurement, ppm
1Н measurement, ppm
HMQC
126.76
HMBC
130.30; 132.51; 122.66
9.52
9.10
8.34
8.17
7.81
7.67
7.41
7.33
6.81
3.42
3.03
142.37
159.12; 141.20; 141.49; 138.56
136.58; 132.51; 128.28; 128.53
137.52
159.12; 141.49; 133.03; 131.17; 127.69; 126.76; 132.51
129.90; 128.28
133.03
151.77; 137.52; 133.03
122.66; 132.51
117.67
112.66
112.66; 123.49
31.02; 28.18
40.00
159.12; 136.56
151.77; 40.00; 112.62
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 11 2009

2410
MEL’NIK et al.
computer simulation of this substance by the molecular
6.81
+
mechanics MM+ method shows that the five-
membered ring of the heterocyclic system has the
envelope structure. In this case the exocyclic double
bond deviates from the plane of the benzoquinoline
fragment by an angle exceeding 30°C. Such spatial
arrangement of the above-described molecule is
confirmed by the absence of a noticeable Overhouser
effect between the olefin proton giving signal at 7.81 ppm
and the proton at 9.52 ppm in the NOESY spectrum.
N(CH3)2
3.03
112.66
40.0
7.41
151.77
133.03
7.81 123.49
7.67
137.52
7.81
8.17
3.42
31.02
28.18
130.03 136.58 9.52
126.76
136.56
The analysis of electron absorption spectra of the
colored products obtained revealed the presence of a
relatively strong absorption band at 560–580 nm.
Compounds with alkyl substituents exhibited the
maximum of the absorption band at about
560 nm with insignificant deviations, while for the
products containing aromatic substituents the maxi-
mum was observed at 580 nm.
159.12
129.90
128.28
3.42
138.56
142.37
9.10
132.51
128.53
122.66
141.20
N
117.67
8.34
149.49
7.81
131.17
127.18
7.33
Studies of formation of molecular orbitals of the
compounds prepared by the reaction of quarternary
salts with p-dimethylaminobenzaldehyde were carried
out by quantum chemical calculations. The formation
of frontier orbitals in the molecules of dyes syn-
thesized results from the interaction of orbitals of the
7.81
130.03
7.81
2
0
–2
–4
–6
–8
–10
–12
–14
–16
Fig. 2. Formation of frontier orbitals in the molecule of dye.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 11 2009

SYNTHESIS AND STUDY OF THE STRUCTURE OF THE REACTION PRODUCTS
Table 4. Energies of frontier moleculer orbitals
2411
EXPERIMENTAL
Molecular
orbital
p-dimethylamino-
UV spectra of the ethanol solutions of substances
were taken on a Specord M-40 spectrometer. 1H NMR
spectra were registered on a Varian Mercury-400
spectrometer (400 MHz) in DMSO-d6 with respect to
internal TMS.
Salt II
Dye VIII
benzaldehyde
LUMO+1
–4.882
–5.558
0.388
–3.876
–5.149
LUMO
HOMO
–0.168
–13.142
–8.273
–10.208
Cyclopenta[c]quinolinium perchlorates I-VI were
prepared according to the procedure [3].
HOMO-1
–13.961
–14.518
7.584
–9.989
–10.408
8.104
–11.879
–12.302
5.059
1-(p-Dimethylaminobenzylidene)-5-methyl-2,3-di-
hydrocyclopenta[c]quinolinium perchlorate (VII).
An equimolar mixture of salt II and p-dimethylamino-
benzaldehyde was heated in acetic anhydride for 0.5 h
at 130°C. The appearance and deepening of the
coloration of the reaction mixture was observed. After
a day of storage the obtained precipitate was treated
with ether and crystallized from aqueous ethanol (1:1).
Compounds VIII–XII were obtained analogously. The
properties of the reaction products and their spectral
characteristics are presented in Table 2.
HOMO-2
LUMO–HOMO
quarternary salts and p-dimethylaminobenzaldehyde.
In the molecules of cyclopenta[c]quinolinium cations
the orbital energy is lower, while in the molecules of
aldehydes it is higher (Fig. 2). HOMO of the dye
molecule is formed mainly from HOMO of aldehyde
because the energy of its orbital is higher. The
decrease in energy of this orbital by 1.9 eV occurs
mainly because of the transition from a neutral
molecule to the molecule of cationic type. The energy
of the aldehyde HOMO-1 corresponding to HOMO-2
in the dye molecule also decreases by 2.4 eV (see
Table 4). LUMO of the dye is formed mainly from the
LUMO of the salt. The energy of the latter slightly
increases (by 0.4 eV) due to the interaction with the
aldehyde orbitals. The difference in the energy
between HOMO and LUMO in the molecule of dye
becomes smaller resulting in the appearance of an
absorption band at about 550 nm which relates to the
first singlet transition from HOMO to LUMO. The
next singlet transitions occur in the UV spectral range
(365 and 300 nm).
REFERENCES
1. Ahl, A.A., Mashlay, M.M., and Metwally, M.A., Bull.
Chim. Farm., 1997, vol. 135, no. 5, p. 297.
2. Mel’nik, M.V., Turov, A.V., Novitski,i Z.L., Stet-
skiv, A.O., and Ganushchak, N.I., Zh. Obshch. Khim.,
2006, vol. 76, no. 4, p. 668.
3. Dorogan, I.V., Ross. Khim. Zh., 2007, vol. 51, no. 5, p. 91.
4. Volovenko, Yu.M. and Turov, O.V., Yadernyi magnit-
nyi resonans (Nuclear Magnetic Resonance), Kiev:
Perun, Irpin’, 2007.
5. Kudinova, M.A., Mel’nik, D.A., Kaxhkovskii, A.D.,
and Tolmachev, A.I., Ukr. Khim. Zh., 2008, vol. 74,
no. 11, p. 57.
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