Synthesis of 1-(9-butylcarbazol-3-yl)-5-oxopyrrolidine-3-carboxylic acid derivatives

Article abstract of DOI:10.1007/s10593-008-0113-6

A series of condensation products of 1-(9-butylcarbazol-3-yl)-5- oxopyrrolidine-3-carbohydrazide with 2-propanone, 2-butanone, 2,4-pentanedione, 2,5-hexanedione, ethyl 3-oxobutanoate, and aromatic aldehydes was obtained. Substituted oxadiazoles were synthesized from carbohydrazide or the corresponding hydrazone. Spectral properties of the synthesized compounds were examined.

Full text of DOI:10.1007/s10593-008-0113-6

Chemistry of Heterocyclic Compounds, Vol. 44, No. 7, 2008
SYNTHESIS OF 1-(9-BUTYLCARBAZOL-
3-YL)-5-OXOPYRROLIDINE-3-CARBOXYLIC
ACID DERIVATIVES
B. Sapijanskaitė, V. Mickevičius
A series of condensation products of 1-(9-butylcarbazol-3-yl)-5-oxopyrrolidine-3-carbohydrazide with
2-propanone, 2-butanone, 2,4-pentanedione, 2,5-hexanedione, ethyl 3-oxobutanoate, and aromatic
aldehydes was obtained. Substituted oxadiazoles were synthesized from carbohydrazide or the
corresponding hydrazone. Spectral properties of the synthesized compounds were examined.
Keywords: 1-(9-butylcarbazol-3-yl)-5-oxopyrrolidine-3-carbohydrazide, 1,3,4-oxa-diazole, pyrazole,
pyrrole, Z-, E-isomers.
In this paper we describe the synthesis of new substituted 9-butylcarbazole derivatives, which contain
5-oxopyrrolidine, 1,3,4-oxadiazole, pyrazole, or pyrrole ring systems, with the aim to obtain new compounds,
which are expected to possess notable chemical and biological activities. Derivatives of 1,3,4-oxadiazole,
5-oxopyrrolidine, pyrazole, and pyrrole are well known to have a wide range of biological activities [1−11], and
carbazole and 1,3,4-oxadiazole derivatives are the most widely employed electron-transporting and hole-
blocking materials [12−16].
The starting product, 1-(9-butylcarbazol-3-yl)-5-oxopyrrolidine-3-carboxylic acid 1, was synthesized
according to the known method by refluxing 3-amino-9-butylcarbazole with itaconic acid in toluene [17]. Later
on 5-oxopyrrolidine 1 was esterified with methanol using sulfuric acid as a catalyst and the resulting ester 2 was
refluxed with hydrazine hydrate in 2-propanol to give hydrazide 3. Condensation of compound 3 with
2-propanone gave the corresponding N'-(propan-2-ylidene)-5-oxopyrrolidine-3-carbohydrazide 4; with 2-buta-
none − N'-(butan-2-ylidene)-5-oxopyrrolidine-3-carbohydrazide 5, and with aromatic aldehydes − 4-arylidene-
hydrazinecarbonyl-1-(9-butylcarbazol-3-yl)-2-pyrrolidinones 6−9.
Monosubstituted 1,3,4-oxadiazole derivative 10 was easily prepared from acid hydrazide 3 by reaction
with an excess of triethyl orthoformate in refluxing mixture. The corresponding hydrazone 7 was oxidatively
cyclized in the presence of oxidant Pb(MeCOO)4 in dichloromethane at +2°C temperature to give 2,5-di-
substituted 1,3,4-oxadiazole derivative 11 in good yield.
1-(9-Butylcarbazol-3-yl)-4-[(3,5-dimethyl-1H-pyrazol-1-yl)carbonyl]pyrro-lidin-2-one 12 was synthe-
sized by condensation of hydrazide 3 with 2,4-pentanedione in ethanol in the presence of a catalytic amount of
hydrochloric acid.
The reaction of hydrazide 3 with ethyl 3-oxobutanoate in refluxing ethanol in the presence of a catalytic
amount of hydrochloric acid gave 3-substituted ethylbutanoate 13, which was separated from the reaction
mixture by column chromatography.
__________________________________________________________________________________________
Kaunas University of Technology, LT-50254 Kaunas, Lithuania; e-mail: Vytautas.Mickevicius@ktu.lt
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1009-1017, July, 2008. Original article
submitted April 13, 2008.
0009-3122/08/4407-0807©2008 Springer Science+Business Media, Inc.
807

Pyrrole derivative 14 was prepared by condensation of hydrazide 3 with 2,5-hexanedione in the
presence of glacial acetic acid as a catalyst in refluxing 2-propanol.
The structures of compounds 1-14 were elucidated on the basis of the elemental analysis data, and IR,
mass, and 1H, 13C NMR spectra.
O
O
O
+
. .
MeOH, H
N2H4 H2O
R
N
R
N
R
N
COOH
COOMe
CONHNH2
2
3
1
1–3 R = 9-butylcarbazol-3-yl
Due to the influence of the substituent in position 4 of the pyrrolidinone ring geminal protons of
methylene COCH2 and NCH2 groups are shielded unequally; therefore their signals in the 1H NMR spectrum are
observed as characteristic doublets and multiplets in the range of 2.90 and 4.07−4.25 ppm, respectively. The
quintet of the CH group proton of pyrrolidinone ring is at 3.56 ppm. Protons of the carbazole moiety resonate in
the range of 7.168.49 ppm, and the butyl group of heterocyclic moiety gives rise to two triplets at 0.95 and
4.43 ppm and two multiplets at 1.331.48 and 1.801.93 ppm. The IR spectrum of compound 1 showed the
expected 2C=O and OH absorptions at 1692, 1731, and 3395 cm−1, respectively. The 1H NMR spectrum of ester
2 exhibits an extensive singlet with integration equivalent to 3 hydrogens at 3.70 ppm due to the methyl group.
When compound 2 was converted to its hydrazide 3, the signals belonging to the hydrazide group were observed
at 9.40 and 4.42 ppm and in the IR spectrum not only absorption bands of C=O at 1653 and 1673 cm−1, but also
broad stretching vibration band in the range of 3307 cm−1 were present.
1
It is evident from the H NMR spectra of compounds 6−9 that in DMSO-d6 solution they exist as a
mixture of Z/E-isomers, the proton signals of which have different intensities due to the possibility of different
arrangements of the substituents with respect to the N=C bond. As a result of stronger shielding, the signals of
the protons of the Z-isomers are observed at higher field [18]. On the basis of the intensities of the signals of the
NH group proton it has been concluded that the Z-isomer always predominates in DMSO-d6 solution. When a
1
less polar solvent, CDCl3, was used to record the H NMR spectrum of compound 8, the proton of NH group
gave a single set of signals at 10.44 ppm.
In contrast to compounds 3, no absorption band corresponding to the NH group was observed in the IR
spectrum of 1,3,4-oxadiazoles 10, 11. Moreover, the signal belonging to carbonyl stretching was absent (CO),
but a new peak at 1595 cm–1 due to the C=N frequency and peaks at 1233 and 1021 cm−1 due to the
1
characteristic stretching vibrations of the =C−O−C= fragment of the oxadiazole ring were present. H NMR
spectra showed peaks due to aromatic protons and other substituents in the expected region (11), and the proton
signal of the CH=N fragment in the oxadiazole moiety was observed downfield at 8.41 ppm (10).
The formation of the pyrazole ring in compound 12 has been proved by the characteristic signal of the
1
proton in position 4 at 6.15 ppm and two singlets of protons of the CH3 groups at 2.23 and 2.53 ppm in the H
NMR spectrum. Characteristic 13C NMR resonances at 153, 145, and 112 ppm were assigned to the
corresponding carbons of pyrazole ring.
1
The H NMR spectrum of compound 13 in (CD3)2CO besides the proton signal characteristic to the
starting compound shows a triplet at 1.22 and a quadruplet at 4.15 ppm assigned to the ethyl group of the ester,
and two singlets of the CH3 and CH2 group protons at 2.09 and 3.40 ppm, respectively. Moreover, broad singlets
of different intensity assigned to the CONH group are observed at 9.63 and 9.78 ppm, which led to the
conclusion that the compound existed as a mixture of E/Z-isomers in (CD)2CO.
808

In the 1H NMR spectrum of compound 14 not only the signal of the NH2 protons at 4.42 ppm is absent,
but also the signal of the CONH group proton is present, while this proton was resonating at lower field (10.97
ppm) in comparison to the spectrum of compound 3. Apart from the signal of the protons of the carbazole and
pyrrolidinone rings, an extensive singlet with integration equivalent to 2 hydrogens characteristic of the CH
fragments of the pyrrole ring at 5.68 ppm and also signals of two methyl groups at 2.03 and 2.04 ppm are
observed.
O
O
R1COR2
R
N
R1
R2
R
N
CONHN=C
CONHNH2
R1CHO
4, 5
3
O
for 7
R
N
Pb(MeCOO)4
CONHN=CHR1
O
6– 9
OMe
O
N
R
N
N
11
O
O
N
HC(OEt)3
N
N
R
10
O
R
N
MeCOCH2COMe
CON
N
Me
12
Me
O
MeCOCH2COOEt
R N
Me
CONHN=CCH2COOEt
13
O
Me
MeCOCH2CH2COMe
R
N
N
CONH
14
Me
3–14 R = 9-butylcarbazol-3-yl; 4 R1 = R2 = Me; 5 R1 = Me;
R2 = Et; 6 R1 = 4-Me2NC6H4; 7 R1 = 4-MeOC6H4;
8 R1 = Ph; 9 R1 = 9-ethylcarbazol-3-yl
809

EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on a Varian Unity Inova 300 spectro-meter (300 and
75 MHz respectively) in (CD3)2CO (compounds 1, 2, 12, 13), DMSO-d6 (compounds 3–7, 9, 11, 14), and CDCl3
(compound 10), operating in Fourier transform mode with TMS as an internal standard. Melting points were
determined on an automatic melting point apparatus APA1 and are uncorrected. The IR spectra were determined
in potassium bromide pellets on a Perkin–Elmer FT-IR system spectrum GX spectrometer. Mass spectral data
were obtained by a Waters (Micromas) ZQ 2000 Spectrometer (APCI, 20 V). Silica gel plates (Silufol UV-254)
were used for analytical purpose. Elemental analysis was carried out on the C,H,N Analyzer CE 440.
1-(9-Butylcarbazol-3-yl)-5-oxopyrrolidine-3-carboxylic acid (1) was prepared according to Ref. [17].
Yield 25.04 g (91%); mp 68−69.5°C (from toluene). IR spectrum, ν, cm−1: 3395 (OH), 1731 (C=O), 1692
1
(C=O). H NMR spectrum, δ, ppm (J, Hz): 0.95 (3H, t, J = 7.3, NCH2CH2CH2CH3); 1.33−1.48 (2H, m,
NCH2CH2CH2CH3); 1.80-1.93 (2H, m, NCH2CH2CH2CH3); 2.90 (2H, d, J = 8.4, COCH2); 3.56 (1H, q, J =8.2,
CH); 4.22-4.34 (2H, m, NCH2); 4.43 (2H, t, J = 7.1, NCH2CH2CH2CH3); 7.16−8.49 (7H, m, HAr). Mass
spectrum (ESI), m/z (Irel, %): 351 [M+H]+ (100). Found, %: C 72.74; H 6.51; N 8.04. C21H22N2O3. Calculated,
%: C 71.98; H 6.33; N 7.99.
Methyl 1-(9-butylcarbazol-3-yl)-5-oxopyrrolidine-3-carboxylate (2). A mixture of 5-oxopyrrolidine
1 (21 g, 60 mmol), methanol (100 ml), and a catalytic amount of conc. H2SO4 was refluxed for 5 h. Then the
solvent was evaporated. The precipitated product was neutralized with 5% sodium bicarbonate solution, filtered
off, and washed with 2-propanol. The crude product was recrystallized from 2-propanol. Yield 15.73 g (72%);
mp 116.5-118°C. IR spectrum, ν, cm−1: 1744 (C=O), 1688 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 0.84 (3H,
t, J = 7.3, NCH2CH2CH2CH3); 1.17-1.33 (2H, m, NCH2CH2CH2CH3); 1.64-1.78 (2H, m, NCH2CH2CH2CH3);
2.70-2.91 (2H, m, COCH2); 3.44-3.59 (1H, m, CH); 3.70 (3H, s, OCH3); 4.09-4.22 (2H, m, NCH2); 4.35 (2H, t,
J = 7.0, NCH2CH2CH2CH3); 7.15-8.31 (7H, m, HAr). 13C NMR spectrum, δ, ppm: 14.44, 20.51, 31.44, 35.89,
35.90, 42.78, 51.61, 52.89, 109.83, 110.12, 113.34, 119.36, 120.31, 121.15, 122.51, 122.67, 126.61, 131.74,
137.98, 141.21, 171.72, 173.99. Mass spectrum (ESI), m/z (Irel, %): 365 [M+H]+ (100). Found, %: C 72.36;
H 6.59; N 7.60. C22H24N2O3. Calculated, %: C 72.51; H 6.64; N 7.69.
1-(9-Butylcarbazol-3-yl)-5-oxopyrrolidine-3-carbohydrazide (3). A mixture of ester 2 (5.1 g,
14 mmol), 2-propanol (20 ml), and 98% hydrazine hydrate (4 ml) was refluxed for 30 min. The reaction mixture
was cooled and the precipitate was filtered off, washed with 2-propanol and ethyl ether, and purified by
recrystallization from ethanol. Yield 3.98 g (78%); mp 181-183°C. IR spectrum, ν, cm−1: 3307 (NH + NH2),
1
1653 (C=O), 1673 (C=O). H NMR spectrum, δ, ppm (J, Hz): 0.84 (3H, t, J = 7.3, NCH2CH2CH2CH3); 1.16-1.34
(2H, m, NCH2CH2CH2CH3); 1.65−1.80 (2H, m, NCH2CH2CH2CH3); 2.73−2.85 (2H, m, COCH2); 3.22-3.51
(1H, m, CH); 4.01-4.17 (2H, m, NCH2); 4.34 (2H, t, J = 7.0, NCH2CH2CH2CH3); 4.42 (2H, s, NH2); 7.16-8.36
(7H, m, HAr); 9.40 (1H, s, NH). Mass spectrum (ESI), m/z (Irel, %): 365 [M+H]+ (100). Found, %: C 69.08;
H 6.58; N 15.12. C21H24N4O2. Calculated, %: C 69.21; H 6.64; N 15.37.
N'-(Propan-2-ylidene)-1-(9-butylcarbazol-3-yl)-5-oxopyrrolidine-3-carbohydrazide (4). To a mixture
of compound 3 (2.0 g, 5.5 mmol) in dry 2-propanone (30 ml) a few drops of concentration hydrochloric acid
were added. The mixture was refluxed for 5 h. The solvent was evaporated under reduced pressure, and the
precipitated product was filtered off, washed with ethyl ether, and purified by recrystallization from ethanol.
1
Yield 1.95 g (88%); mp 135-137°C. IR spectrum, ν, cm−1: 3193 (NH), 1696 (C=O), 1681 (C=O). H NMR
spectrum, δ, ppm (J, Hz): 0.89 (3H, t, J = 7.3, NCH2CH2CH2CH3); 1.23-1.37 (2H, m, NCH2CH2CH2CH3);
1.69-1.82 (2H, m, NCH2CH2CH2CH3); 1.90 (45%), 1.92 (55%) (3H, 2s, Z/E N=CCH3 1.97 (3H, s, Z+E
N=CCH3); 2.64-2.85 (2H, m, COCH2); 4.00-4.25 (3H, m, NCH2+CH); 4.41 (2H, t, J = 7.0, NCH2CH2CH2CH3);
810

7.15-8.35 (7H, m, HAr); 10.28, 10.33, 10.38 (1H, 3s, Z/E NH). Mass spectrum (ESI), m/z (Irel, %): 405 [M+H]+
(100). Found, %: C 71.32; H 6.84; N 13.57. C24H28N4O2. Calculated, %: C 71.26; H 6.98; N 13.85.
N'-(Butan-2-ylidene)-1-(9-butylcarbazol-3-yl)-5-oxopyrrolidine-3-carbohydrazide (5). A mixture of
hydrazide 3 (2.0 g, 5.5 mmol) and 2-butanone (12 ml) was refluxed for 8.5 h. The solvent was evaporated under
reduced pressure till dryness; the oily product was triturated with ethyl ether. The obtained solid was filtered off,
washed with ethyl ether, and crystallized from 2-propanone. Yield 1.94 g (85%); mp 149-151°C. IR spectrum, ν,
−
1
1
cm : 3193 (NH), 1697 (C=O), 1677 (C=O). H NMR spectrum, δ, ppm (J, Hz): 0.86 (3H, t, J = 7.3,
NCH2CH2CH2CH3); 1.04 (34%), 1.05 (66%) (3H, 2t, J = 7.4, Z/E N=CCH2CH3); 1.20-1.35 (2H, m,
NCH2CH2CH2CH3); 1.67-1.80 (2H, m, NCH2CH2CH2CH3); 1.87 (50%), 1.89 (37%), 1.93 (13%) (3H, 3s, Z+E
N=CCH3); 2.20-2.36 (2H, m, N=CCH2CH3); 2.69-2.82 (2H, m, COCH2); 3.95-4.23 (3H, m, NCH2 + CH); 4.38
(2H, t, J = 7.0, NCH2CH2CH2CH3); 7.15-8.32 (7H, m, HAr); 10.23, 10.38 (1H, 2s, Z/E NH). 13C NMR spectrum,
δ, ppm: 10.23, 10.66, 13.59, 15.94, 19.64, 30.57, 31.31, 31.42, 33.26, 34.50, 35.51, 41.88, 51.10, 51.83, 108.96,
109.24, 112.38, 112.45, 118.44, 119.39, 119.49, 120.28, 121.59, 121.76, 125.71, 131.02, 137.02, 140.30,
154.28, 159.40, 168.62, 171.73, 173.73. Mass spectrum (ESI), m/z (Irel, %): 419 [M+H]+ (100). Found, %:
C 71.62; H 7.27; N 13.38. C25H30N4O2. Calculated, %: C 71.74; H 7.22; N 13.39.
Hydrazones 6−9 (General Method). A mixture of hydrazide 3 (2.0 g, 5.5 mmol), the corresponding
aldehyde (5.5 mmol), and ethanol (15-30 ml) was refluxed for 2-3 h. The reaction mixture was cooled and the
precipitate was filtered off and washed with ethanol and hexane.
N'-{[4-(Dimethylamino)phenyl]methylidene}-1-(9-butylcarbazol-3-yl)-5-oxopyrrolidine-3-carbo-
hydrazide (6). Yield 2.31 g (85%); mp 210-212°C (ethanol). IR spectrum, ν, cm−1: 3221 (NH), 1671 (C=O),
1681 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 0.85 (63%), 0.86 (37%) (3H, 2t, J = 7.3, Z/E
NCH2CH2CH2CH3); 1.19-1.34 (2H, m, NCH2CH2CH2CH3); 1.67-1.79 (2H, m, NCH2CH2CH2CH3); 2.75−2.87
(2H, m, COCH2); 2.93, 2.96 (6H, 2s, N(CH3)2); 4.05-4.29 (3H, m, NCH2 + CH); 4.37 (2H, t, J = 7.1,
NCH2CH2CH2CH3); 6.68-8.34 (12H, m, HAr + N=CH); 11.31, 11.36 (1H, 2s, Z/E NH). 13C NMR spectrum, δ,
ppm: 13.90, 19.95, 30.88, 33.31, 34.93, 35.26, 42.25, 51.54, 51.98, 109.28, 109.55, 112.00, 112.87, 118.78,
119.89, 120.59, 121.97, 122.13, 126.03, 128.30, 128.59, 131.32, 131.40, 137.40, 140.66, 144.58, 147.98,
151.52, 168.30, 171.80, 173.24. Mass spectrum (ESI), m/z (Irel, %): 496 [M+H]+ (100). Found, %: C 72.63;
H 6.67; N 13.98. C30H33N5O2. Calculated, %: C 72.70; H 6.71; N 14.13.
N'-[(4-Methoxyphenyl)methylidene]-1-(9-butylcarbazol-3-yl)-5-oxopyrrolidine-3-carbohydrazide
(7). Yield 1.64 g (62%); mp 195−197°C (ethanol). IR spectrum, ν, cm−1: 3206 (NH), 1686 (C=O), 1662 (C=O).
1H NMR spectrum, δ, ppm (J, Hz): 0.87 (63%), 0.88 (37%) (3H, 2t, J = 7.3, Z/E NCH2CH2CH2CH3); 1.22-1.37
(2H, m, NCH2CH2CH2CH3); 1.69-1.82 (2H, m, NCH2CH2CH2CH3); 2.75−2.90 (2H, m, COCH2); 3.77, 3.79
(3H, 2s, OCH3); 4.08-4.30 (3H, m, NCH2 + CH); 4.36 (2H, t, J = 7.0, NCH2CH2CH2CH3); 6.94−8.35 (12H, m,
HAr + N=CH); 11.48, 11.55 (1H, 2s, Z/E NH). 13C NMR spectrum, δ, ppm: 13.62, 19.69, 30.62, 33.01, 34.67,
35.02, 35.42, 41.98, 51.22, 51.64, 55.17, 109.01, 109.28, 112.53, 112.62, 114.22, 118.52, 119.52, 119.63,
120.33, 121.71, 121.86, 125.77, 126.66, 128.36, 128.60, 131.10, 137.14, 140.39, 143.42, 146.82, 160.57,
160.77, 168.46, 171.28, 171.49, 173.00. Mass spectrum (ESI), m/z (Irel, %): 483 [M+H]+ (100). Found, %:
C 72.01; H 6.25; N 11.58. C29H30N4O3. Calculated, %: C 72.18; H 6.27; N 11.61.
N'-(Phenylmethylidene)-1-(9-butylcarbazol-3-yl)-5-oxopyrrolidine-3-carbohydrazide (8). Yield
1
1.56 g (63%); mp 199-200°C (ethanol). IR spectrum, ν, cm−1: 3178 (NH), 1712 (C=O), 1677 (C=O). H NMR
spectrum (DMSO-d6), δ, ppm (J, Hz): 0.86 (57%), 0.87 (43%) (3H, 2t, J = 7.3, Z/E NCH2CH2CH2CH3);
1.21-1.38 (2H, m, NCH2CH2CH2CH3); 1.68-1.81 (2H, m, NCH2CH2CH2CH3); 2.77−2.91 (2H, m, COCH2);
4.09-4.30 (3H, m, NCH2 + CH); 4.39 (2H, t, J = 7.0, NCH2CH2CH2CH3); 7.18-8.39 (13H, m, HAr + N=CH);
11.61, 11.68 (1H, 2s, Z/E NH). 13C NMR spectrum, δ, ppm: 13.35, 19.41, 30.34, 32.72, 34.38, 34.77, 41.70,
50.89, 51.30, 108.75, 109.02, 112.27, 112.36, 118.25, 119.37, 120.05, 121.42, 121.57, 125.49, 126.51, 126.72,
128.46, 129.52, 130.80, 133.77, 136.87, 140.12, 143.27, 146.65, 168.42, 170.97, 171.16, 173.36. 1H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 0.92 (3H, t, J = 7.2, NCH2CH2CH2CH3); 1.28-1.43 (2H, m, NCH2CH2CH2CH3);
811

1.75-1.87 (2H, m, NCH2CH2CH2CH3); 2.98-3.24 (2H, m, COCH2); 4.14-4.40 (3H, m, NCH2 + CH); 4.26 (2H, t,
J = 7.1, NCH2CH2CH2CH3); 7.17−8.23 (13H, m, HAr + N=CH); 10.44 (1H, s, NH). Mass spectrum (ESI), m/z
(Irel, %): 453 [M+H]+ (100). Found, %: C 74.19; H 6.22; N 12.26. C28H28N4O2. Calculated, %: C 74.31; H 6.24;
N 12.38.
N'-[(9-Ethylcarbazol-2-yl)methylidene]-1-(9-butylcarbazol-3-yl)-5-oxopyrrolidine-3-carbohydra-
zide (9).Yield 1.06 g (34%); mp 144-146°C (ethanol). IR spectrum, ν, cm−1: 3203 (NH), 1682 (C=O). 1H NMR
spectrum, δ, ppm (J, Hz): 0.84 (53%), 0.85 (47%) (3H, 2t, J = 7.3, Z/E NCH2CH2CH2CH3); 1.29 (3H, t, J = 7.3,
NCH2CH3); 1.15-1.38 (2H, m, NCH2CH2CH2CH3); 1.63-1.79 (2H, m, NCH2CH2CH2CH3); 2.81-2.98 (2H, m,
COCH2); 3.39-3.53 (1H, m, CH); 4.10-4.38 (4H, m, NCH2CH3 + NCH2); 4.44 (2H, t, J = 7.0,
NCH2CH2CH2CH3); 7.10-8.54 (15H, m, HAr+N=CH); 11.56, 11.63 (1H, 2s, Z/E NH). Mass spectrum (ESI), m/z
(Irel, %): 570 [M+H]+ (100). Found, %: C 75.70; H 6.05; N 12.08. C36H35N5O2. Calculated, %: C 75.90; H 6.19;
N 12.29.
1-(9-Butylcarbazol-3-yl)-4-(1,3,4-oxadiazol-2-yl)pyrrolidin-2-one (10). A mixture of compound 3
(3.0 g, 8.2 mmol) and triethyl orthoformate (15 ml) was refluxed for 24 h. After cooling, the obtained oily
viscous liquid was washed with water and decanted. The residue was dissolved in chloroform, the solution was
dried over Na2SO4 and filtered off, and the solvent was removed on a rotary evaporator. The obtained crude
material was chromatographed over a silica gel column (propanone−hexane, 1.5:1). Rƒ 0.73. Yield 1.39 g
1
(45%); mp 161-162°C. IR spectrum, ν, cm−1: 1702 (C=O), 1595 (C=N), 1233, 1020 (=C–O–C=). H NMR
spectrum, δ, ppm (J, Hz): 0.86 (3H, t, J = 7.3, NCH2CH2CH2CH3); 1.22-1.35 (2H, m, NCH2CH2CH2CH3);
1.67-1.79 (2H, m, NCH2CH2CH2CH3); 2.88-3.08 (2H, m, COCH2); 3.82−3.95 (1H, m, CH); 4.12-4.22 (4H, m,
NCH2CH2CH2CH3 + NCH2); 7.15-8.13 (7H, m, HAr); 8.41 (1H, s, CH). 13C NMR spectrum, δ, ppm: 13.70,
20.28, 28.37, 30.47, 36.03, 42.61, 52.15, 108.71, 108.81, 113.22, 118.72, 119.68, 120.33, 122.28, 122.48,
125.86, 130.05, 137.92, 140.72, 153.63, 166.34, 170.54. Mass spectrum (ESI), m/z (Irel, %): 375 [M+H]+ (100).
Found, %: C 70.52; H 6.10; N 14.85. C22H22N4O2. Calculated, %: C 70.57; H 5.92; N 14.96.
1-(9-Butylcarbazol-3-yl)-4-[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]pyrrolidin-2-one (11). To an
ice-cooled (to 2°C) magnetically stirred vessel 40 ml dichloromethane Pb(MeCOO)4 (1.77 g, 4 mmol) was
added and the contents stirred for 5 min. Then hydrazone 7 (0.96 g, 2 mmol) was added in portions. The reaction
mixture was stirred at +2°C for 8 h. Then it was filtered off and dichloromethane was removed on a rotary
evaporator. The crude product was poured into water and the mixture was heated up to the boiling point;
afterwards, the mixture was cooled and the water was decanted. The obtained crude material was
chromatographed over a silica gel column (acetylacetate−hexane−methanol, 6:3:1). Rƒ 0.62. Yield 0.58 g (61%);
mp 109-110°C. IR spectrum, ν, cm−1: 1699 (C=O), 1613 (C=N), 1265, 1020 (=C−O−C=). 1H NMR spectrum, δ,
ppm (J, Hz): 0.85 (3H, t, J = 7.3, NCH2CH2CH2CH3); 1.19-1.35 (2H, m, NCH2CH2CH2CH3); 1.66-1.80 (2H, m,
NCH2CH2CH2CH3); 2.98−3.18 (2H, m, COCH2); 3.83 (3H, s, OCH3); 4.15-4.27 (1H, m, CH); 4.30-4.48 (4H,
m, NCH2CH2CH2CH3 + NCH2); 7.10−8.35 (11H, m, HAr). 13C NMR spectrum, δ, ppm: 14.14, 20.22, 28.55,
31.14, 36.25, 42.51, 52.26, 55.93, 109.57, 109.84, 113.29, 115.23, 116.22, 119.09, 120.20, 120.82, 122.25,
122.38, 126.33, 128.84, 131.35, 137.78, 140.94, 162.42, 164.86, 166.90, 171.19. Mass spectrum (ESI), m/z
(Irel, %): 481 [M+H]+ (100). Found, %: C 72.62; H 5.92; N 11.47. C29H28N4O3. Calculated, %: C 72.48; H 5.87;
N 11.66.
1-(9-Butylcarbazol-3-yl)-4-[(3,5-dimethylpyrazol-1-yl)carbonyl]pyrrolidin-2-one (12). A mixture
of hydrazide 3 (1.0 g, 2.7 mmol), 2,4-pentanedione (0.92 g, 9.1 mmol), ethanol (12 ml), and catalytic amount of
hydrochloric acid was refluxed for 3 h. The solvent was evaporated under reduced pressure to dryness, and the
oily product was triturated with ethyl ether. The obtained solid was filtered off and washed with ethyl ether. The
crude product was purified by column chromatography (acetone−hexane, 1:2). Rƒ 0.52. Yield 0.77g (66%); mp
120-121°C. IR spectrum, ν, cm−1: 1735 (C=O), 1693 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 0.91 (3H, t, J = 7.3,
NCH2CH2CH2CH3); 1.30-1.44 (2H, m, NCH2CH2CH2CH3); 1.77-1.90 (2H, m, NCH2CH2CH2CH3); 2.23, 2.53 (6H,
2s, 2CH3); 2.85-3.04 (2H, m, COCH2); 4.18-4.43 (2H, m, NCH2); 4.39 (2H, t, J = 7.2, NCH2CH2CH2CH3);
812

4.56−4.68 (1H, m, CH); 6.15 (1H, s, C=CH); 7.15−8.37 (7H, m, HAr). 13C NMR spectrum, δ, ppm: 14.60, 14.88,
15.14, 21.73, 32.61, 36.55, 37.71, 43.98, 52.97, 110.38, 110.72, 112.90, 113.98, 120.23, 121.10, 121.91, 124.06,
124.26, 127.38, 133.41, 139.24, 142.57, 145.77, 153.94, 172.44, 174.39. Mass spectrum (ESI), m/z (Irel, %): 429
[M+H]+ (100). Found, %: C 72.71; H 6.45; N 12.98. C26H28N4O2. Calculated, %: C 72.87; H 6.59; N 13.07.
Ethyl 3-{[(5-oxo-1-(9-butylcarbazol-3-yl)pyrrolidin-3-yl)carbonyl]hydrazono}butanoate (13). A
mixture of hydrazide 3 (2.0 g, 5.5 mmol), ethyl 3-oxobutanoate (0.71 g, 5.5 mmol), ethanol (25 ml), and a
catalytic amount of hydrochloric acid was refluxed for 7.5 h. Then it was cooled, and the precipitated product
was filtered off, washed with ethanol, and purified by column chromatography (acetone−hexane, 1:2). Rƒ 0.68.
Yield 1.88 g (72%); mp 99−101°C. IR spectrum, ν, cm−1: 3276 (NH), 1731 (C=O), 1695 (C=O), 1669 (C=O).
1H NMR spectrum, δ, ppm (J, Hz): 0.91 (3H, t, J = 7.3, NCH2CH2CH2CH3); 1.22 (3H, t, J = 7.5, COOCH2CH3);
1.30-1.44 (2H, m, NCH2CH2CH2CH3); 1.78-1.90 (2H, m, NCH2CH2CH2CH3); 2.09 (3H, s, CH3); 2.71−2.95
(2H, m, COCH2); 3.40 (2H, s, CH2COOCH2CH3); 4.00−4.29 (3H, m, NCH2+CH); 4.15 (2H, q, J = 7.2,
COOCH2CH3); 4.40 (2H, t, J = 7.2, NCH2CH2CH2CH3); 7.13−8.39 (7H, m, HAr); 9.63, 9.78 (1H, 2s, NH). Mass
spectrum (ESI), m/z (I, %): 477 [M+H]+ (100). Found, %: C 68.06; H 6.79; N 11.70. C27H32N4O4. Calculated, %:
C 68.05; H 6.77; N 11.76.
1-(9-Butylcarbazol-3-yl)-N-(2,5-dimethylpyrrol-1-yl)-5-oxopyrrolidine-3-carboxamide (14). To a
solution of hydrazide 3 (1.0 g, 2.7 mmol) in 2-propanol (14 ml) 2,5-hexanedione (0.78 g, 6.8 mmol) and glacial
acetic acid (0.5 ml) were added. The reaction mixture was stirred and refluxed for 2 h. Then it was cooled to
room temperature. The precipitated product was filtered off, washed with ethyl ether and recrystallized from
2-propanol. Yield 0.86 g (71%); mp 183−184°C. IR spectrum, ν, cm−1: 3261 (NH), 1687 (C=O), 1666 (C=O). 1H
NMR spectrum, δ, ppm (J, Hz): 0.86 (3H, t, J = 7.3, NCH2CH2CH2CH3); 1.21-1.35 (2H, m, NCH2CH2CH2CH3);
1.68-1.80 (2H, m, NCH2CH2CH2CH3); 2.03, 2.04 (6H, 2s, 2CH3); 2.73-2.98 (2H, m, COCH2); 3.48-3.62 (1H, m,
CH); 4.09-4.32 (2H, m, NCH2); 4.38 (2H, t, J = 6.5, NCH2CH2CH2CH3); 5.68 (2H, s, 2CH); 7.15-8.37 (7H, m,
HAr); 10.97 (1H, s, NH). 13C NMR spectrum, δ, ppm: 10.94, 13.68, 19.74, 30.67, 34.32, 35.44, 42.02, 51.50,
103.05, 109.12, 109.36, 112.80, 118.60, 119.72, 120.39, 121.75, 121.87, 125.86, 126.71, 130.94, 137.26, 140.45,
171.04, 171.98. Mass spectrum (ESI), m/z (Irel, %): 443 [M+H]+ (100). Found, %: C 73.05; H 6.86; N 12.31.
C27H30N4O2. Calculated, %: C 73.28; H 6.83; N 12.66.
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