Vanillin esters in reactions with indan-1,3-dione

Article abstract of DOI:10.1007/s10593-006-0229-5

2-Methoxy-4-(12-oxo-12H-benzo[f]indeno[1,2-b]quinolin-13-yl)phenyl esters of carboxylic acids were synthesized by the three component condensation of indan-1,3-dione, 2-naphthylamine, and O-acylvanillin. 2-Arylidenindan-1,3-diones formed during the reaction were isolated. Springer Science+Business Media, Inc. 2006.

Full text of DOI:10.1007/s10593-006-0229-5

Chemistry of Heterocyclic Compounds, Vol. 42, No. 9, 2006
VANILLIN ESTERS IN REACTIONS
WITH INDAN-1,3-DIONE
N. G. Kozlov and L. I. Basalaeva
2-Methoxy-4-(12-oxo-12H-benzo[f]indeno[1,2-b]quinolin-13-yl)phenyl esters of carboxylic acids were
synthesized by the three component condensation of indan-1,3-dione, 2-naphthylamine, and
O-acylvanillin. 2-Arylidenindan-1,3-diones formed during the reaction were isolated.
Keywords: 2-arylidenindan-1,3-diones, O-acylvanillins, indan-1,3-dione, 2-methoxy-4-(12-oxo-12H-
benzo[f]indeno[1,2-b]quinolin-13-yl)phenyl esters of carboxylic acids, 2-naphthylamine.
Thanks to its high reactivity, indan-1,3-dione is widely used in synthetic organic chemistry, including
the synthesis of heterocyclic compounds [1, 3].
In the present work we have presented the results of a study of a three component condensation of indan-
1,3-dione 1, 2-naphthylamine 2, and vanillin esters 3a-h. The condensation was carried out by heating equimolar
amounts of the components in ethanol. We assumed that formation of the final heterocyclic compound of the
indenoquinoline series occurred via intermediate amino ketone A, which then lost a water molecule and cyclized
to the corresponding 4-(12,13-dihydro-12-7H-benzo[f]indeno[1,2-b]quinolin-13-yl)-2-methoxyphenyl esters of
the carboxylic acids 5a-h. Oxidation of the latter gave 2-methoxy-4-(12-oxo-12H-benzo[f]indeno[1,2-
b]quinolin-13-yl)phenyl esters of the carboxylic acids 6a-h.
In all the experiments under the experimental conditions the esters 5a-h were found in mixtures with
2-methoxy-4-(12-oxo-12H-benzo[f]indeno[1,2-b]quinolin-13-yl)phenyl esters of the carboxylic acids 6a-h in a
1
ratio of 1:9 according to the H NMR spectra. At recrystalization of compounds 5a-h their further oxidation
occurs and separation of them from the reaction mixture in pure form proved impossible. In view of the
difficulty of separating compounds 5a-h and 6a-h, immediate dehydration of the mixture obtained by boiling in
nitrobenzene for 3-4 h was carried out.
During monitoring of the course of the reaction we established that 4-[(1,3-dihydro-1,3-dioxo-2H-inden-
2-ylidene)methyl]-2-methoxyphenyl esters of the carboxylic acids 4a-h were always present in the reaction
mixture. From this it can be proposed that condensed reaction products of the dihydrobenzoindenoquinoline
series 5a-h are formed by reaction of the 2-arylideneindan-1,3-diones 4a-h with 2-naphthylamine 2.
To confirm this idea we have synthesized 4-[(1,3-dihydro-1,3-dioxo-2H-inden-2-ylidene)methyl]-2-
methoxyphenyl esters of the carboxylic acids 4a-h by the reaction of indan-1,3-dione with O-acylvanillins 3a-h
and condensing them with 2-naphthylamine 2 under analogous conditions. Mixtures of the esters 5a-h and 6a-h
were formed as a result of the condensation, analogous to the mixtures from the three component condensation
of compounds 1, 2, and 3a-h.
__________________________________________________________________________________________
Institute of Physicoorganic Chemistry, Belarus National Academy of Sciences, Minsk 220072, Belarus;
e-mail: loc@ifoch.bas-net.by. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, 1408-1413,
September, 2006. Original article submitted February 25, 2004; revision submitted March 17, 2006.
0009-3122/06/4209-1223©2006 Springer Science+Business Media, Inc.
1223

OMe
NH2
R
O
,
O
O
3a–h
O
2
1
O
R
O
3a–h
O
O
O
OMe
2
O
N
O
MeO
O
R
A
4a–h
OMe
OMe
O
R
O
O
R
O
O
O
N
N
6a–h
5a–h
3,4,6 a R = Me, b R = Et, c R = Pr, d R = i-Pr, e R = Bu, f R = Am, g R = Hex, h R = Hept
The synthesized esters 6a-h are crystalline substances with a yellowish color (Table 1).
The IR spectra of compounds 4a-h contain intense absorption bands in the 1580-1600 cm-1 region, due
to stretching vibrations of carbonyl groups conjugated to the benzene ring, and absorption bands of similar
intensity in the 1740-1760 cm-1 region due to ester carbonyl groups. In the IR spectra of compounds 6a-h there
are absorption bands of medium intensity at 1560-1580 cm-1 ascribed to stretching vibrations of carbonyl groups
conjugated to benzene and naphthalene nuclei, while the ester carbonyl groups give intense absorptions in the
1710-1730 cm-1 range.
Analysis of the mass spectra of compounds 4a-h and 6a-h indicates the stability of these compounds to
electron impact. In the mass spectra of compounds 4a-h and 6a-h there are high intensity molecular ion peaks
[M+] (I 100%) and satisfactorily intense peaks for ions with m/z 120 (I = 40-50%) for compounds 4a-h, and with
m/z = 281 (I = 60 -70%) for compounds 6a-h, corresponding to the ions [M - CH3OC6H3OCOR]+.
1
The H NMR spectra of compounds 6a-h (Table 2) correspond to a benzoindenoquinoline structure in
the position and multiplicity of the signals of the aromatic protons. The methine proton of compounds 4a-h
is conjugated with two carbonyl group, appears at weak field in the spectra as a singlet at 8.74-8.85 ppm, which
corresponds with the position of the methine proton in the spectra of analogous compounds [4].
1224

TABLE 1. Characteristics of Compounds 4a-h and 6a-h
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
mp, °С
Yield, %
69
C
H
N
4a
С19Н14О5
70.78
70.80
4.39
4.35
—
163
4b
4c
4d
4e
4f
С20Н16О5
71.38
71.43
72.03
72.00
71.98
72.00
72.55
72.53
73.07
73.01
73.44
73.46
73.91
73.89
78.16
78.20
78.45
78.43
78.61
78.65
78.65
78.65
78.90
78.85
79.00
79.04
79.25
79.22
79.37
79.39
4.73
4.76
5.13
5.14
5.09
5.14
5.46
5.49
5.80
5.82
6.15
6.12
6.37
6.40
4.31
4.27
4.61
4.57
4.83
4.86
4.88
4.86
5.10
5.13
5.36
5.39
5.67
5.63
5.88
5.86
—
—
—
—
—
—
—
160
140
62
67
52
49
48
50
58
75
64
74
72
70
57
54
50
С21Н18О5
С21Н18О5
162-164
130-132
126-127
128
С22Н20О5
С23Н22О5
4g
4h
6a
6b
6c
6d
6e
6f
С24Н24О5
С25Н26О5
124
С29Н19NО4
С30Н21NО4
С31Н23NО4
С31Н23NО4
С32Н25NО4
С33Н27NО4
С34Н29NО4
С35Н31NО4
3.11
3.15
3.02
3.05
3.01
2.96
2.97
2.96
2.90
2.87
2.81
2.79
2.75
2.72
2.68
2.65
236
250
252
274
281
280
6g
6h
273
279
TABLE 2. 1H NMR Spectra of Compounds 4a-h and 6a-h
Chemical shifts, δ, ppm (J, Hz)
Com-
pound
СН ОCH3
(1Н, s) (3Н, s)
R
4
HAr
5
1
2
3
4а
4b
4c
8.85
4.00
2.20 (3Н, s, CH3)
7.20 (1Н, s); 7.70 (3Н, m);
8.10 (2Н, m)
8.75
8.74
4.00
3.98
1.25 (3Н, t, J = 6.9, СН2СН3);
2.75 (2Н, q, J = 6.7, СН2СН3)
7.30 (1Н, d, J = 7.8); 7.82 (1Н, s);
7.91 (3Н, m); 8.00 (2Н, m)
1.09 (3Н, t, J = 6.4, (СН2)2СН3);
1.75 (2Н, m, СН2СН2СН3);
7.15 (1Н, d, J = 8.2); 7.83 (1Н, s);
7.90 (3Н, m); 8.00 (2Н, m)
2.59 (2Н, t, J = 6.7, СН2СН2СН3)
4d
4e
8.72
8.75
3.99
4.00
1.30 (6Н, d, J = 6.8, (СН3)2СН);
2.80 (1Н, m, (СН3)2СН)
7.19 (1Н, d, J = 8.0); 7.85 (1Н, s);
7.93 (3Н, m); 8.00 (2Н, m)
1.0 (3Н, t, J = 6.5, (СН2)3СН3);
1.50 (2Н, m, (СН2)2СН2СН3);
1.75 (2Н, m, СН2СН2СН2СН3);
2.60 (2Н, t, J = 7.0, СН2(СН2)2СН3)
7.15 (1Н, d, J = 8.2); 7.82 (1Н, s);
7.89 (3Н, m); 8.00 (2Н, m)
4f
8.77
8.75
4.00
4.00
1.0 (3Н, t, J = 6.9, (СН2)4СН3);
1.45 (4Н, m, (СН2)2СН2СН2СН3);
1.75 (2Н, m, СН2СН2(СН2)2СН3);
2.58 (2Н, t, J = 6.8, СН2(СН2)3СН3)
7.15 (1Н, d, J = 7.8); 7.84 (1Н, s);
7.87 (3Н, m); 8.00 (2Н, m)
4g
0.98 (3Н, t, J = 6.4, (СН2)5СН3);
1.42-1.78 (8Н, m, СН2(СН2)4СН3);
2.55 (2Н, t, J = 6.7, СН2(СН2)4СН3)
7.15 (1Н, d, J = 8.3); 7.85 (1Н, s);
7.89 (3Н, m); 8.00 (2Н, m)
1225

TABLE 2 (continued)
1
2
3
4
5
4h
8.73
3.96
0.96 (3Н, t, J = 6.5, (СН2)6СН3);
1.40-1.80 (10Н, m, СН2(СН2)5СН3);
2.50 (2Н, t, J = 6.3, СН2(СН2)5СН3)
7.13 (1Н, d, J = 8.0); 7.82 (1Н, s);
7.86 (3Н, m); 8.04 (2Н, m)
6а
—
3.75
2.18 (3Н, s, CH3)
6.73 (1Н, d, J = 7.8); 7.00 (1Н, s);
7.20 (2Н, m); 7.50 (3Н, m);
7.68 (1Н, d, J = 7.4);
7.75 (1Н, t, J = 6.5);
7.87 (1Н, d, J = 8.2);
8.00 (3Н, m)
6b
6c
—
—
3.73
3.75
1.22 (3Н, t, J = 6.4, СН2СН3);
2.67 (2Н, q, J = 7.0, СН2СН3)
6.90 (1Н, d, J = 7.8); 7.08 (1Н, s);
7.22 (2Н, m); 7.50 (3Н, m);
7.65 (1Н, d, J = 7.4); 7.73 (1Н, t,
J = 6.7); 7.85 (1Н, d, J = 8.2);
8.10 (3Н, m)
1.04 (3Н, t, J = 6.7, (СН2)2СН3);
1.62 (2Н, m, СН2СН2СН3 );
2.52 (2Н, t, J = 6.4, СН2СН2СН3)
6.95 (1Н, d, J = 7.4);
6.98 (1Н, s); 7.12 (2Н, m);
7.63 (3Н, m); 7.70 (1Н, d,
J = 8.2); 7.79 (1Н, t, J = 6.7);
7.92 (1Н, d, J = 8.0);
8.13 (3Н, m)
6d
6e
6f
—
—
—
—
—
3.72
3.73
3.75
3.72
3.74
1.30 (6Н, d, J = 6.8, (СН3)2СН);
2.78 (1Н, m, (СН3)2СН)
6.82 (1Н, d, J = 8.0); 7.00 (1Н, s);
7.25 (2Н, m); 7.48 (3Н, m);
7.60 (1Н, d, J = 7.9); 7.73 (1Н, t,
J = 6.3); 7.92 (1Н, d, J = 8.2);
8.10 (3Н, m)
1.0 (3Н, t, J = 6.6, (СН2)3СН3);
1.43-1.75 (4Н, m, СН2(CH2)2СН3);
2.60 (2Н, t, J = 6.7, СН2(СН2)2СН3)
6.76 (1Н, d, J = 7.8); 6.98 (1Н, s);
7.02 (2Н, m); 7.43 (3Н, m);
7.65 (1Н, d, J = 8.2); 7.70 (1Н, t,
J = 6.4); 7.84 (1Н, d, J = 7.6);
8.16 (3Н, m)
1.0 (3Н, t, J = 6.5, (СН2)4СН3);
1.40-1.60 (6Н, m, СН2(СН2)3СН3);
2.58 (2Н, t, J = 6.3, СН2(СН2)3СН3) 7.62 (1Н, d, J = 7.5); 7.84 (1Н, t,
6.93 (1Н, d, J = 7.9); 7.15 (1Н, s);
7.27 (2Н, m); 7.50 (3Н, m);
J = 6.8); 8.03 (1Н, d, J = 8.2);
8.16 (3Н, m)
6g
6h
0.98 (3Н, t, J = 6.7, (СН2)5СН3);
1.42-1.78 (8Н, m, СН2(СН2)4СН3);
2.55 (2Н, t, СН2(СН2)4СН3)
6.90 (1Н, d, J = 7.9); 7.05 (1Н, s);
7.34 (2Н, m); 7.52 (3Н, m);
7.65 (1Н, d, J = 7.7); 7.79 (1Н, t,
J = 6.7); 7.95 (1Н, d, J = 7.9);
8.17 (3Н, m)
0.98 (3Н, t, J = 6.5, (СН2)5СН3);
1.52-1.76 (8Н, m, СН2(СН2)4СН3);
2.50 (2Н, t, J = 6.5, СН2(СН2)4СН3)
6.75 (1Н, d, J = 7.6); 7.00 (1Н, s);
7.31 (2Н, m); 7.54 (3Н, m);
7.66 (1Н, d, J = 7.9); 7.73 (1Н, t,
J = 6.3); 7.93 (1Н, d, J = 7.6);
8.08 (3Н, m)
EXPERIMENTAL
Mass spectra were recorded with a Finnigan MAT INCOS 50 (70 eV). IR spectra were recorded with a
Nicolet Protege Fourier spectrometer. 1NMR spectra of DMSO-d6 solutions with TMS as internal standard were
recorded with Bruker AC-500 (500 MHz) and Tesla BS-567 (100 MHz) spectrometers. Melting points were
determined with a Kofler block.
O-Acylvanillins 3a-h. Absolute pyridine (0.25 mol) and the corresponding acid chloride (0.20 mol)
(added in small portions), prepared by boiling the carboxylic acid (1 mol), SOCl2 (1.3 mol), and absolute
benzene (500 ml) for 6 h, followed by removal of the benzene, and distilling the residue, were added to a stirred
solution of vanillin (0.2 mol) in absolute CH2Cl2 (500 ml). The reaction mixture was boiled for 1 h, the CH2Cl2
1226

was evaporated off on a water bath, the residue was dissolved in benzene (500 ml), washed with water twice,
washed with 5% aqueous NaHCO3 three times, and dried over CaCl2. The solvent was distilled off and the
residue was distilled or recrystallized from a 1:1 mixture of benzene and hexane.
1
Compound 3a. Yield 92%; mp 78-79°C (mp 77-79°C [5]). H NMR spectrum, δ, ppm (J, Hz): 2.32
(3H, s, CH3); 3.92 (3H, s, OCH3); 7.18 (1H, d, J = 7.1, Harom); 7.48 (2H, m, Harom); 9.92 (1H, s, CHO).
Compound 3b. Yield 79%; mp 33-34°C .1H NMR spectrum, δ, ppm (J, Hz): 1.25 (3H, t, J = 6.9,
CH2CH3); 2.52 (2H, q, J = 6.7, CH2CH3); 3.84 (3H, s, OCH3); 7.13 (1H, d, J = 7.4, Harom); 7.42 (2H, m, Harom);
9.88 (1H, s, CHO). Found, %: C 63.29; H 5.73. C11H12O4. Calculated, %: C 63.46; H 5.77.
20
1
Compound 3c. Yield 81%; bp 137-138°C (0. 5 mm Hg), nD 1.5281. H NMR spectrum, δ, ppm
(J, Hz): 1.02 (3H, t, J = 6.2, (CH2)2CH3, 1.63 (2H, m, CH2CH2CH3); 2.51 (2H, t, J = 6.7, CH2CH2CH3); 3.84
(3H, s, OCH3); 7.15 (1H, d, J = 7.7, Harom); 7.40 (2H, m, Harom); 9.90 (1H, s, CHO). Found, %: C 64.11; H 7.02.
C12H16O4. Calculated, %: C 64.28; H 7.14.
Compound 3d. Yield 89%; mp 29-30°C .1H NMR spectrum, δ, ppm (J, Hz): 1.35 (6H, d, J = 6.8,
CH(CH3)2); 2.88 (1H, m, CH(CH3)2); 3.90 (3H, s, OCH3); 7.21 (1H, d, J = 7.5, Harom); 7.50 (2H, m, Harom); 9.96
(1H, s, CHO). Found, %: C 64.72; H 6.19. C12H14O4. Calculated, %: C 64.86; H 6.31.
Compound 3e. Yield 76%; bp 149-150°C (0.5 mm Hg), nD20 1.5273. 1H NMR spectrum, δ, ppm (J, Hz):
0.96 (3H, t, J = 6.8, (CH2)3CH3); 1.20-1.90 (4H, m, 2CH2); 2.62 (2H, t, J = 6.5, CH2(CH2)2CH3); 3.96 (3H, s,
OCH3); 7.15 (1H, d, J = 7.8, Harom); 7.38 (2H, m, Harom); 9.90 (1H, s, CHO). Found, %: C 66.01; H 6.62.
C13H16O4. Calculated, %: 66.10; H 6.77.
Compound 3f. Yield 85%; bp 155-156°C (0.5 mm Hg); nD20 1.5068. 1H NMR spectrum, δ, ppm (J, Hz):
0.90 (3H, t, J = 6.2, (CH2)4CH3); 1.12-1.90 (6H, m, 3CH2); 2.58 (2H, t, J = 6.5, CH2(CH2)3CH3); 3.88 (3H, s,
OCH3); 7.13 (1H, d, J = 7.3, Harom); 7.44 (2H, m, Harom); 9.95 (1H, s, CHO). Found, %: C 67.19; H 7.23.
C14H18O4. Calculated, %: 67.20; H 7.20.
20
1
Compound 3g. Yield 82%; bp 163-164°C (0.5 mm Hg); nD 1.5092. H NMR spectrum, δ, ppm
(J, Hz): 0.96 (3H, t, J = 6.3, (CH2)5CH3); 1.15-1.88 (8H, m, 4CH2); 2.51 (2H, t, J = 6.5, CH2(CH2)4CH3); 3.86
(3H, s, OCH3); 7.12 (1H, d, J = 7.0, Harom); 7.45 (2H, m, Harom); 9.91 (1H, s, CHO). Found, %: C 68.22; H 7.59.
C15H20O4. Calculated, %: 68.18; H 7.57.
20
1
Compound 3h. Yield 77%; bp 170-171°C (0.5 mm Hg); nD 1.5079. H NMR spectrum, δ, ppm
(J, Hz): 0.92 (3H, t, J = 6.4, (CH2)6CH3); 1.32-1.64 (10H, m, 5CH2); 2.60 (2H, m, CH2(CH2)5CH3); 3.88 (3H, s,
OCH3); 7.14 (1H, d, J = 7.2, Harom); 7.47 (2H, m, Harom); 9.90 (1H, s, CHO). Found, %: C 68.83; H 7.69.
C16H22O4. Calculated, %: 69.06; H 7.91.
Interaction of Indan-1,3-dione 1,2-Naphthylamine 2, and O-Acylvanillin Alkanoates 3a-h (General
Method). A solution of 2-naphthylamine 2 (1.43 g, 0.01 mol) in ethanol (10 ml) and a solution of the
corresponding ester 3a-h (0.01 mol) in ethanol (10 ml) were added to a solution of indan-1,3-dione 1 (0.01 mol)
in ethanol (10 ml). The reaction mixture was boiled for 30-60 min. The precipitate which formed when the
mixture was cooled was separated, added to nitrobenzene (15 ml), and boiled for 3-4 h. The solvent was
evaporated, and the solid residue was washed with ether and crystallized from a 1:3 mixture of ethanol and
benzene.
Synthesis of 4-[(1,3-Dihydro-1,3-dioxo-2H-inden-2-ylidene)methyl]-2-methoxyphenyl Esters of
Carboxylic Acids 4a-h (General Method). A mixture of indan-1,3-dione 1 (1.46 g, 0.01 mol) and the
corresponding O-acylvanillin 3a-h (0.01 mol) in ethanol (20 ml) was boiled for 2-3 h. The precipitate was
separated and crystallized from butanol.
This work was supported by a grant from the Belorussian Republic Fund for Fundamental Research
(grant XO3-079).
1227

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1228