A 1H, 13C and 15N NMR spectroscopic and GIAO DFT study of ethyl 5-oxo-2-phenyl-4-(2-phenylhydrazono)-4,5-dihydro-1H-pyrrole-3-carboxylate

Article abstract of DOI:10.1016/j.tetlet.2010.04.043

¹⁵N-Labelled ethyl 5-oxo-2-phenyl-4-(2-phenylhydrazono)-4,5-dihydro-1H-pyrrole-3-carboxylate was synthesized by azo-coupling of diazotized aniline (using Na¹⁵NO₂, 99% ¹⁵N) with ethyl 4,5-dihydro-5-oxo-2-phenyl-(1H)-pyrrole-3-carboxylate. The product was formed as a tautomeric hydrazone mixture as confirmed by ¹³C and ¹⁵N chemical shifts, and was obtained as a mixture of E and Z isomers according to ⁿJ(¹⁵N, ¹³C). A comparison of the ¹H NMR data with GIAO DFT calculations enabled determination of the configuration of the carboxy ester group in both isomers.

Full text of DOI:10.1016/j.tetlet.2010.04.043

Tetrahedron Letters 51 (2010) 3149–3151
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1
A H, 13C and 15N NMR spectroscopic and GIAO DFT study of ethyl
5-oxo-2-phenyl-4-(2-phenylhydrazono)-4,5-dihydro-1H-pyrrole-3-carboxylate
a,b,
c
c
a
c
*
ˇ
ˇ
, Stanislav Lunák Jr. , Tarek Aysha , Radim Holuša , Radim Hrdina
Antonín Lycka
a Research Institute for Organic Syntheses (VUOS), Rybitví 296, CZ-533 54 Pardubice 20, Czech Republic
b University of Hradec Králové, Faculty of Education, Rokitanského 62, CZ 500 03 Hradec Králové 3, Czech Republic
c Faculty of Chemical Technology, University of Pardubice, Studentská 95, CZ-532 10 Pardubice, Czech Republic
a r t i c l e i n f o
a b s t r a c t
15N-Labelled ethyl 5-oxo-2-phenyl-4-(2-phenylhydrazono)-4,5-dihydro-1H-pyrrole-3-carboxylate was
synthesized by azo-coupling of diazotized aniline (using Na15NO2 , 99% 15N) with ethyl 4,5-dihydro-5-
oxo-2-phenyl-(1H)-pyrrole-3-carboxylate. The product was formed as a tautomeric hydrazone mixture
as confirmed by 13C and 15N chemical shifts, and was obtained as a mixture of E and Z isomers according
to nJ(15N, 13C). A comparison of the 1H NMR data with GIAO DFT calculations enabled determination of the
configuration of the carboxy ester group in both isomers.
Article history:
Received 3 February 2010
Revised 24 March 2010
Accepted 12 April 2010
Available online 18 April 2010
Keywords:
Tautomerism
Isomerization
NMR
Ó 2010 Elsevier Ltd. All rights reserved.
GIAO
Ethyl
4,5-dihydro-5-oxo-2-phenyl-1H-pyrrole-3-carboxylate
the proton and carbon resonances. It was found, based on 13C
(1, pyrrolinone ester) is a virtually undetectable intermediate in
the synthesis of diketo-pyrrolo-pyrrole (DPP) pigment (C.I. Pig-
ment Red 255) from benzonitrile and diethyl succinate.1 If synthe-
sized independently,2 the pyrrolinone ester can undergo, due to
the presence of a strongly activated methylene group at position
4, reaction with the aromatic nitrile forming unsymmetrical DPPs,3
or condensation with aromatic aldehydes,4 carboxy esters and
chlorides5 or oxidative dimerization,2 giving rise to various types
of new dyes or pigments.
Both the condensation of pyrrolinone ester 1 with phenylhydr-
azine and azo-coupling with diazotized aniline result in the same
product, as previously reported.6 Since the structural details of
the products were not described,6 and because of our interest in
dyes based on a pyrrolinone ester,3,4c we decided to study the reac-
tion product of the azo-coupling with a pyrrolinone ester 1 in de-
tail (Scheme 1).
The diazotization of aniline was carried out by the usual proce-
dure,7 and diazotization using Na15NO2 (99% 15N8) was accom-
plished in the same way. The azo-coupling reaction gave product
2 in moderate yield and good purity.9
Ethyl 5-oxo-2-phenyl-4-(2-phenylhydrazono)-4,5-dihydro-1H-
pyrrole-3-carboxylate (2) exists as a mixture of two components
in DMSO-d6, the content of which can change slightly over time.
Two-dimensional NMR experiments10 allowed assignment of all
and 15N chemical shifts,11 that both components existed com-
pletely as the hydrazones.
The existence of two components in the reaction mixture was
due to the presence of two geometric isomers. The 2J(15N, 13C) cou-
pling constant values were used to assign the Z and E isomers. The
values of the 2J(15N, 13C) coupling constants for the (nearly) planar
arrangement differed considerably (Fig. 1) and were not affected to
any great extent by the character of the substituents.12 It was nec-
essary to use the 15N-labelled compound and good digital resolu-
tion during the 13C NMR spectral measurements in order to
determine the nJ(15N, 13C) coupling constants precisely. The most
important values are those of 2J(15N, 13C) for carbons 3 and 5.
The results are collected in Table 1.
Rather surprisingly, the largest difference between the 1H chem-
ical shifts of the E and Z isomers was found for the methylene group,
and especially the methyl protons of the ethoxy group, which are
relatively distant from the C@N bond. In order to explain these dif-
ferences we modelled the structure of both isomers using density
functional theory (DFT: B3LYP/6-311G(d,p)) and computed theoret-
ical 1H chemical shifts by the gauge-including atomic orbital (GIAO)
method.13 Both methods were adopted from the GAUSSIAN03W pro-
gram suite.14 Two conformations were found for each isomer, differ-
ing in the orientation of the carboxy ester group with respect to the
pyrrolinone ring (Fig. 2). The difference between the total energies of
the most stable conformations of each isomer [(Z), s-cis and (E),
s-trans] was low, which explains the simultaneous appearance of
both isomers in the reaction mixture. The 4-(2-phenylhydrazono)-
* Corresponding author. Fax: +420 466823900.
E-mail addresses: antonin.lycka@vuos.com, antonin.lycka@seznam.cz (A. Lycka).
ˇ
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.04.043

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A. Lycka et al. / Tetrahedron Letters 51 (2010) 3149–3151
3150
4´
3´
2´
O
3
+ Cl-
15N
N
1´
O
O
O
2
O
O
H
N
1
+
2´´
+
4
N
15N
N
5
H
N
15N
3´´
4´´
N
1´´
H
H
O
H
O
O
1
(Z)-2
(E)-2
Scheme 1. Azo-coupling reaction with compound 1 and atom numbering in the reaction products.
Table 1
2J(15N,13C)
1H, 13C and 15N chemical shifts and nJ(15N, 13C) coupling constants (Hz, 0.3 Hz) of the
(E) and (Z) isomers of compound 2 measured in DMSO-d6
C
C
H/C/N
(E)-2
d (1H) d (13C)
(Z)-2
nJ(15N, 13C) d (1H) d (13C)
nJ(15N, 13C)
1-3 Hz
7-13 Hz
15N
1
2
3
11.31 ꢀ224.6a
11.41 ꢀ232.6a
—
156.0
99.0
2.6
3.2
—
146.5
102.4
129.8
161.3
129.8
129.6
128.1
130.2
162.3
59.7
3.7
7.5
6.0
<1
Figure 1. Typical absolute values of the 2J(15N, 13C) coupling constants in nearly
planar systems depending on the orientation of the carbon atoms with respect to
the nitrogen atom electron lone pair.
—
—
4
—
—
—
7.57
7.51
7.51
—
4.09
0.92
—
128.9
164.3
131.0
129.9
127.9
130.3
166.0
61.0
7.4
12.1
—
—
—
7.64
7.51
7.51
—
4.20
1.25
—
5
10
20
30
pyrrolinone is quasiplanar in all cases, and the pendant 2-phenyl
group is significantly rotated out of plane (44–53°). Rotation of the
carboxy ester group with respect to the pyrrolinone ring is moder-
ate, the highest rotation being (26°) for the least stable (E), s-cis con-
former, which is the only one not stabilized by an intramolecular
NH–CO hydrogen bond.
40
3-COO
OCH2
CH3
4-(@N)–NH–
13.3
14.1
ꢀ40.1a
ꢀ34.7a
@N–NH–
13.00 ꢀ215.4a
13.10 ꢀ217.3a
100
200
300
400
—
142.8
114.2
129.1
122.8
6.5
2.3
—
142.8
114.2
129.1
122.8
6.5
2.4
Only one value of the 1H chemical shift was found experimentally
for the two (three) protons of the methylene (methyl) group which
indicates that free rotation of the ethyl group on the NMR time-scale
must occur. On the other hand, the different average values for both
isomers prove the stabilized position of the carboxy ester group. The
GIAO-computed values were very similar for the s-trans and s-cis
conformers of both isomers, showing that the 1H chemical shifts of
the ethyl protons depend only on the conformation of the carboeth-
oxy group with respect to the pyrrolidinone ring. Finally, the differ-
7.30
7.43
7.08
7.47
7.43
7.12
a
d (15N).
ence between the values for both isomers infers that the
conformation of the carboxy ester is different in both. The theoreti-
cal values match the experimental values significantly better for the
Figure 2. DFT-computed structures of both conformations of the carboethoxy group of the E and Z isomers of 2, together with the relative total energies and GIAO NMR and
experimental 1H chemical shifts of the methylene and methyl groups.

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A. Lycka et al. / Tetrahedron Letters 51 (2010) 3149–3151
3151
9. Ethyl 4,5-dihydro-5-oxo-2-phenyl(1H)pyrrole-3-carboxylate (1, 0.33 g,
(Z), s-cis and (E), s-trans arrangements (Fig. 2), in accordance with
thermodynamic stability. Thus we consider the chemical outcome
displayed in Scheme 1 as definitely proved. The preference for the
(Z), s-cis conformer was also the situation for the structurally similar
isopropyl 1-phenyl-4-phenylhydrazono-5-oxo-3-pyrazolecarboxy-
late according to X-ray diffractometry.15
1.43 mmol) was dissolved in MeOH (25 ml), the mixture was cooled to 0 °C
and the solution of the diazonium salt was added dropwise. The reaction
mixture was stirred at 0–5 °C for 4 h and then at the rt for 12 h. The
precipitated dye was filtered, washed with MeOH and H2O and recrystallized
from EtOH. Yield 63%, mp 193–195 °C. Anal. Calcd (C19H17N3O3): C, 68.05; H,
5.11; N, 12.53. Found: C, 68.10; H, 5.28; N, 12.63. Positive-ion MS: m/z 336
[M+H]+, 100%; 290 [M+HꢀC2H5OH]+. Negative-ion MS: m/z 334 [MꢀH]ꢀ, 100%;
288 [MꢀHꢀC2H5OH]ꢀ.
10. The 1H and 13C NMR spectra were recorded on
a Bruker Avance II 400
Acknowledgement
spectrometer (operating at 400.13 MHz for 1H, and 100.62 MHz for 13C) in
DMSO-d6. The 1H and 13C chemical shifts were referenced to internal TMS
(d = 0.00). All 2D experiments (gradient-selected gs-COSY, gs-HMQC, gs-HMBC)
were performed using Topspin 2.1. The 15N NMR spectra were recorded on a
Bruker Avance II 400 spectrometer at 40.54 MHz and the 15N chemical shifts
were referenced to external nitromethane (d = 0.0).
This research was supported by the Ministry of Education,
Youth and Sports of the Czech Republic (grant VZ MSMT No.
0021627501).
ˇ
ˇ
11. (a) Lycka, A. Annu. Rep. NMR Spectrosc. 1993, 26, 247; (b) Lycka, A. Annu. Rep.
NMR Spectrosc. 2000, 42, 1.
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Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken,
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1.43 mmol) in water (10 ml) was added dropwise over 20 min. The mixture
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8. Aldrich (99% 15N).
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