Efficient synthesis of novel pyranoquinoline derivatives from simple acetanilide derivatives: Experimental and theoretical study of their physicochemical properties using DFT calculations

Article abstract of DOI:10.5935/0103-5053.20140103

A convenient reaction of 2-chloroquinoline-3-carbaldehyde derivatives and dimedone in the presence of KF-Al₂O₃ for the synthesis of useful pyranoquinolines is described. Reasonable yields (41-50percent), easily available starting materials and less expensive efficient catalyst are the key features of the present method. A mechanism was proposed for the reaction course. Attribution of the chemical shifts was made with the help of the density functional theory (DFT) calculations. The computed nuclear magnetic resonance (NMR) chemical shifts are in good agreement with available experimental data. The nucleus-independent chemical shift (NICS) values were used as quantitative measures for the relative aromatic character in pyranoquinolines. The calculated NICS values obtained for the phenyl group of pyranoquinoline compounds are smaller than that of benzene. ?2014 Sociedade Brasileira de Qui?mica.

Full text of DOI:10.5935/0103-5053.20140103

http://dx.doi.org/10.5935/0103-5053.20140103
J. Braz. Chem. Soc., Vol. 25, No. 7, 1253-1260, 2014.
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Article
A
Efficient Synthesis of Novel Pyranoquinoline Derivatives from Simple Acetanilide
Derivatives: Experimental and Theoretical Study of their Physicochemical
Properties using DFT Calculations
Zohreh Mirjafary,a Hamid Saidian,*,b Morteza Sahandib and Leila Shojaeib
aDepartment of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran
bDepartment of Science, Payame Noor University (PNU), PO Box 19395-4697, Tehran, Iran
Uma reação conveniente para sintetizar piranoquinolinas úteis a partir de derivados de
2-cloroquinolina-3-carbaldeído e dimedona na presença de KF-Al2O3 é descrita. Rendimentos
razoáveis (41-50%), matérias-primas facilmente encontradas e catalisador eficiente pouco
caro são os destaques deste método. Foi proposto um mecanismo de reação. A atribuição dos
deslocamentos químicos foi feita com ajuda de cálculos de teoria do funcional da densidade
(DFT). Os deslocamentos químicos de ressonância magnética nuclear (NMR) calculados têm boa
concordância com dados experimentais.Valores de deslocamento químico independente de núcleo
(NICS) foram usados como medida quantitativa do caráter aromático relativo de piranoquinolinas.
Os valores calculados de NICS do grupo fenila de compostos piranoquinolínicos são menores
que aqueles do benzeno.
A convenient reaction of 2-chloroquinoline-3-carbaldehyde derivatives and dimedone in
the presence of KF-Al2O3 for the synthesis of useful pyranoquinolines is described. Reasonable
yields (41-50%), easily available starting materials and less expensive efficient catalyst are the key
features of the present method. A mechanism was proposed for the reaction course. Attribution of
the chemical shifts was made with the help of the density functional theory (DFT) calculations.
The computed nuclear magnetic resonance (NMR) chemical shifts are in good agreement with
available experimental data. The nucleus-independent chemical shift (NICS) values were used
as quantitative measures for the relative aromatic character in pyranoquinolines. The calculated
NICS values obtained for the phenyl group of pyranoquinoline compounds are smaller than that
of benzene.
Keywords: quinoline, pyranoquinoline, Knoevenagel condensation, aromaticity, DFT
calculations
Introduction
biological activities including antiviral, antitumor, and
mutagenicity activities.3 However, an extensive literature
survey reveals that sufficient efforts have not been made to
combine these heterocycles, pyranoquinolines, in the same
molecular scaffold.4 Pyranoquinolines possess a wide range
of interesting biological activities, such as anti-allergic,
anti-inflammatory, psychotropic, and estrogenic activities.5
Thus, the development of an efficient method for their
synthesis still attracts much interest.
KF-Al2O3 was introduced by Clark as a solid base and
has been applied as catalyst to a wide variety of organic
synthesis. Several recent articles have reviewed this field.6
The strongly basic nature of KF-Al2O3 allows it to replace
organic bases in a number of reactions. In the context of our
general interest in the synthesis of heterocycles,7 herein, we
The quinoline nucleus comprises a class of heterocycles,
which has been exploited more immensely than any other
nucleus for the development of potent drugs. A range
of pharmacological properties, such as antibacterial,
antitumor, anti-inflammatory, antimalarial, antioxidant,
antimicrobial and antifungal activities of this important
class of heterocycles are found in the literature (Figure 1).1
Additionally, quinolinederivativesfinduseinthesynthesisof
fungicides, biocides, alkaloids, rubber chemicals, flavoring
agents and as antifoaming agent in refineries.2 On the other
hand, pyran derivatives possess a wide-range spectrum of
*e-mail: h_porkaleh@yahoo.com

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Efficient Synthesis of Novel Pyranoquinoline Derivatives from Simple Acetanilide Derivatives
J. Braz. Chem. Soc.
Figure 1. Some quinoline-containing bioactive compounds.
propose a facile synthesis of pyranoquinoline derivatives 5
using KF-Al2O3 as an efficient, commercially available
and non-toxic catalyst (Scheme 1). Good yield and low
cost of the reagents are the salient features of this method.
The reaction starts from easily accessible starting material,
which makes it an interesting process for the preparation
of pyranoquinolines 5. 2-Chloroquinoline-3-carbaldehyde
derivatives are very useful starting material for synthesis of
a wide variety of heterocycles8 and can be easily synthesized
from acetanilide derivatives withVilsmeyer-Haack reaction.9
Additionally, a combination of experimental and
density functional theory (DFT) calculations was also
used to investigate their physicochemical properties,
such as nuclear magnetic resonance (NMR) data, and
aromaticity. It was shown that DFT methods perform
NMR spectra calculations very well and give accurate
results.10 On the other hand, aromaticity is a vital property
of conjugated cyclic molecules in the determination of
their structure, reactivity, and stability. Aromaticity is not
a directly measurable or computable quantity.11 Among
the magnetic criteria, nucleus-independent chemical shift
(NICS) continues to gain popularity as an easily computed,
generally applicable criterion to characterize aromaticity and
antiaromaticity of different compounds.12 NICS is computed
as the negative magnetic shielding at selected points at the
ring center, above or below the ring. Negative NICS values
indicate aromaticity, whereas positive values indicate
antiaromaticity, and small values represent non-aromaticity.
It is recommended that the NICS(1) (at points 1 Å above
the ring center) to be the best measure of the π-electron
delocalization in a cyclic molecule.13 In this paper we use
NICS as quantitative measures for aromatic character in
pyranoquinolines 5. The 1H NMR and 13C NMR chemical
shifts of pyranoquinolines (5a) were also determined by DFT
calculations with the help of full spectral analysis.
Experimental
General information
All chemicals required for the synthesis of pyrano-
quinolines 5 were purchased from Fluka (Neu-Ulm,
Scheme 1. Efficient synthesis of pyranoquinolines.

Vol. 25, No. 7, 2014
Mirjafary et al.
1255
Germany), Sigma-Aldrich (St. Louis, MO, USA),
and Merck (Darmstadt, Germany) and were used as
received. The KF-Al2O3 support was prepared according
to previously reported procedure.6 The synthesized
compounds 5 all gave satisfactory spectroscopic data.
A Bruker (DRX-400 Avance) NMR was used to record
stirred for 10 min, which resulted in yellow precipitation
of the desired 2-chloroquinoline-3-carbaldehydes 3. The
precipitate was filtered and washed with water and then
dried. The compounds were purified by recrystallization
from ethyl acetate.
1
the H NMR and 13C NMR spectra. All NMR spectra
General procedure for synthesis of pyranoquinolines 5
were determined in CDCl3 at ambient temperature. Gas
chromatography-mass spectrometry (GC-MS) (Agilent
HP 6890, electron ionization (EI), 70 eV, HP-5 column
(30 m × 0.25 mm × 0.2 µm), HP 5793 mass selective
detector) was used to record the mass spectra.
To a stirred suspension of 100 mg KF-Al2O3 in
acetonitrile (5 mL) were added 2-chloroquinoline-3-
carbaldehyde 3 (1 mmol) and dimedone (140 mg, 1 mmol).
The reaction mixture was stirred at 80-90 °C for 10 h.
The progress of the reaction was monitored by thin layer
chromatography (TLC). After completion of the reaction,
the solvent was removed under reduced pressure, and
the residue was separated by preparative TLC (eluent:
petroleum ether/ethyl acetate 5:1) to afford the desired
compound 5.
Computational methods
All geometry optimizations and frequency calculations
of all species were carried out using the Gaussian 03
program.14 Density functional theory with the Becke
three parameters hybrid functional (DFT-B3LYP)
calculations were performed with a 6-31+G(d,p) basis set.
Vibrational frequencies were calculated at the same level
to ensure that each stationary point is a real minimum.
Harmonic oscillator approximation was also used for
the thermodynamic partition functions. After geometry
optimization and frequency calculations, zero-point
energies (ZPEs) and thermal corrections were obtained
at 298 K. The NMR computations were performed
using the gauge-independent atomic orbital (GIAO) and
continuous set of gauge transformations (CSGT) methods.15
NICS values are calculated at 1 Å above the plane of the
optimized compounds, NICS(1), using the GIAO method
at B3LYP/6-31+G(d, p).
Results and Discussion
Synthesis
The 2-chloroquinoline-3-carbaldehyde derivatives 3
were prepared from the corresponding substituted
acetanilide 2 and Vilsmeyer-Haack agent (DMF + POCl3)
with high yields and excellent purity at 80-90 °C (Table 1).
To find the optimal conditions for the synthesis of
pyranoquinolines 5, reaction of 2-chloroquinoline-3-
carbaldehyde 3a and dimedone 4 in the presence of a base
was chosen as a model reaction.A mixture of 3a (1 mmol),
dimedone 4 (1 mmol), and solvent (5 mL) was stirred under
various reaction conditions. Our first experiment showed
that the presence of a base such as K2CO3 or KF-Al2O3 is
required to achieve the synthesis of 5a. K2CO3 was less
effective compared to KF-Al2O3. We then continued to
optimize the model reaction by considering the efficiency
of polar and nonpolar solvents. A polar solvent such as
CH3CN was much better than a nonpolar solvent. The effect
of temperature was also studied by carrying out the model
reaction at room temperature and 80-90 °C. It was observed
that the yield was increased as the reaction temperature
was raised to 80 °C. The structures of the products were
General procedure for synthesis of acetanilide 2
To a solution of 60 mL water and 8 mL aniline
(0.08 mol) were added 10 mL acetic anhydride (0.1 mol).
The reaction mixture was stirred at 40-50 °C for 30 min.
After completion of the reaction, the mixture was poured
into ice-cold water and stirred for 10 min, which resulted
in precipitation of acetanilide 2. The solid precipitate was
filtered, washed with 30 mL of cold water, and then dried.
1
General procedure for synthesis of 2-chloroquinoline-3-
confirmed by EI-MS, H NMR, and 13C NMR analysis
1
carbaldehydes 3
(see Supplementary Information). The H NMR and 13C
NMR spectra of the product clearly indicated the formation
1
To stirred DMF (3.6 mL, 46 mmol), 12.5 mL POCl3
(134 mmol) were added dropwise at 0-5 °C. The mixture
was allowed to stir for 30 min. Acetanilide 2 (18.5 mmol)
was then added and the resulting solution heated for 12 h at
80-90 °C. The mixture was poured into ice-cold water and
of 5a. The characteristic signals for 5a in the H NMR
spectra were a singlet for the protons of methyl groups at
1.22 ppm, a singlet for CH2 protons of dimedone ring at
2.56 ppm, and a doublet signal for the vinyl proton of the
dimedone ring at 5.54 ppm. The presence of this signal in

1256
Efficient Synthesis of Novel Pyranoquinoline Derivatives from Simple Acetanilide Derivatives
J. Braz. Chem. Soc.
Table 1. Synthesis of 2-chloroquinoline-3-carbaldehyde derivatives 3
entry
Acetanilide 2
Product 3
Yield / %
1
89
86
74
2
3
4
83
the 1H NMR spectra of the synthesized compounds is a good
indication of the formation of the desired compounds. A
sharp and deshielded signal for the vinyl proton of pyran
at 7.21 ppm and five peaks for the aromatic protons at
7.22-7.88 ppm are the other characteristic signals in the
1H NMR spectrum of 5a. The 13C NMR and distortionless
enhancement by polarization transfer (DEPT) 135 spectra
of 5a showed 17 distinct resonances in agreement with
the proposed structure, at d = 196.56 ppm resonance for
the carbonyl carbon, 13 distinct resonances for aromatic
and vinylic carbons between d = 116.25-159.08 ppm, a
resonance at d = 53.18 ppm for the methylene carbon, a
resonance at d = 33.42 ppm for the quaternary carbon of
dimedone and a sharp resonance at d = 30.51 ppm for the
carbons of methyl groups. EI-MS spectrum of 5a clearly
showed the presence of the molecular ion (M+•, m/z 277)
with relative high abundance and other expected fragments.
Direct elimination of methyl moiety from M+• yielded ion
at m/z 262 as base peak in EI-MS spectrum. This fragment
can be stabilized by the aromatic system (Scheme 2).
To generalize this method, we used a series of
2-chloroquinoline-3-carbaldehyde derivatives to obtain
their corresponding pyranoquinolines 5 (Table 2).As shown
in Table 2, all the substrates consistently underwent reaction
to the desired pyranoquinolines 5 in moderate yields.
A plausible mechanism for the present reaction to
produce pyranoquinolines 5 is proposed in Scheme 3.
In the first step, dimedone can undergo a Knoevenagel
condensation with 2-chloroquinoline-3-carbaldehyde 4
in refluxing CH3CN to afford the intermediate I with the
release of H2O. Subsequently, the ring closures proceed
through an addition-elimination reaction to give the desired
pyranoquinolines 5 under reaction conditions.
Computational results
NMR calculations
Atom numbering in accordance with molecular
structure of pyranoquinoline 5a is given in Figure 2. A
main important goal of this part is to properly assign
Scheme 2. Stabilization of ion at m/z 262 as base peak by the aromatic system in EI-MS spectrum.

Vol. 25, No. 7, 2014
Mirjafary et al.
1257
Table 2. Synthesis of novel pyranoquinolines 5
entry
2-Chloroquinoline-3-carbaldehydes 3
Pyranoquinolines 5
Yield / %
50
1
2
3
4
46
44
41
Scheme 3. Possible mechanism for the formation of novel pyranoquinolines 5.
the experimental NMR data to the computed data
of 5a.
At first, the geometry of the molecule was optimized.
1
After that, H NMR and 13C NMR chemical shifts
calculations were performed using B3LYP/6-31+G(d,p).
Chemical shifts were reported in parts per million relative
1
to tetramethylsilane (TMS) for H NMR and 13C NMR
spectra. Relative chemical shifts were calculated by using
the corresponding TMS shielding calculated at the same
theoretical level as the reference. The relations between the
Figure 2. Atom numbering in accordance with the molecular structure
of pyranoquinoline 5a.

1258
Efficient Synthesis of Novel Pyranoquinoline Derivatives from Simple Acetanilide Derivatives
J. Braz. Chem. Soc.
experimental 1H and 13C chemical shifts (dexp) and magnetic
isotropic shielding constants (dcalc) are usually linear and
(Table 4). An account for the decrease of the aromaticity
in such systems is lower resonance energies per π electron
than benzene. Their values are close to the ideal aromaticity
index (NICS(1) = −10.2 ppm) stated by the NICS model
for benzene.
described by the following equation: dexp = a + b dcalc
.
The slope and intercept of the least-square correlation are
utilized to predict chemical shifts. The relative 1H and 13C
chemical shifts were calculated by two methods: Gauge-
Independent Atomic Orbital (GIAO) and Continuous Set
of Gauge Transformations (CSGT) (Table 3). According
to the comparison between experimental and calculated
Table 4. NICS values for the phenyl group and summation of the NICS
(NICS(1) and ∑NICS(1), respectively) at 1 Å above the phenyl group of
pyranoquinoline systems 5 calculated at GIAO- B3LYP/6-31+G(d,p) level
1
data, the calculated H chemical shifts are in acceptable
Pyranoquinoline 5
NICS(1)
−9.8937
−9.1881
−9.4087
−8.9147
∑ NICS(1)
−15.0573
−13.9780
−14.6380
−13.4848
agreement with the experimental results obtained by the
GIAO method. The determination coefficient for proton
chemical shifts in GIAO method is determined to be 0.9976
as shown in Figure 3.
5a
5b
5c
5d
Table 3. Representative computed B3LYP/6-31+G(d,p) 1H and 13C
chemical shifts for pyranoquinoline 5a (see Supplementary Information)
Interestingly, the aromaticity of the phenyl group
of pyranoquinoline systems 5 was deeply affected
by substitution. Generally, substitution decreases the
aromaticity of the phenyl group of pyranoquinolines 5
compared to benzene. NICS values predict decreasing
and increasing effects for the electron donating group
(such as OCH3, with NICS(1) = −8.9147 ppm, Table 4,
entry 4) and electron withdrawing groups (such as Br with
NICS(1) = −9.4087 ppm, Table 4, entry 3), respectively.
It should be mentioned that the NICS index does not
allow the aromaticity of a polycyclic conjugated system
like pyranoquinoline systems 5 to be estimated directly.
On the other hand, it is not easy to know how to use NICS
values for different ring systems to handle a global property
like aromaticity. Schleyer et al., in 2001, introduced the
summation of the NICS values as a global aromaticity
index.16 As a result, the summation of NICS values for a
given polycyclic system produces a single quantity called
the “total NICS”. Therefore, in this study the sum of the
NICS calculated at 1 Å above the rings, ∑ NICS(1), is
also used to evaluate the aromaticity of each molecule
as a whole (Table 4). As shown in Table 4, substitution
decreases the aromaticity of pyranoquinoline systems 5
and the unsubstituted pyranoquinoline 5a is proposed as
the most aromatic compound among 4 species. On the other
hand, methoxide as an electron donating moiety decreases
the aromaticity of pyranoquinoline 5d.
Theoretical chemical shift / ppm
Experimental
chemical
shift / ppm
Atom
GIAO
CSGT
H14
H22
H26
H29
H36
C20
C21
C24
C28
7.54
2.26
5.71
1.21
7.88
2.56
5.57
3.99
5.54
1.19
0.48
1.22
7.18
5.06
7.21
190.77
53.54
36.46
30.65
194.79
55.22
34.41
32.15
196.56
53.18
33.42
30.51
1
Figure 3. Determination coefficient for H chemical shifts in GIAO
method for pyranoquinoline 5a.
Conclusions
Aromaticity calculations
This study also includes benzene molecule calculations
for comparison and study of the addition effect of the ring
on the aromaticity properties (NICS) of benzene. The results
show that NICS for the phenyl group of pyranoquinoline
compounds 5 are less than that for benzene, as expected
In summary, we have described a simple and efficient
protocol for the synthesis of novel pyranoquinoline
derivatives in moderate yields. The synthesis is based on
the Knoevenagel condensation of dimedone to various
2-chloroquinoline-3-carbaldehydes, followed by an

Vol. 25, No. 7, 2014
Mirjafary et al.
1259
addition-elimination reaction. Additionally, NICS as
quantitative measure for aromatic character and 1H NMR
and 13C NMR chemical shifts of pyranoquinolines were
also determined by DFT calculations with the help of
full spectral analysis. The results show that NICS for the
phenyl group of pyranoquinoline molecules 5 are less than
that for benzene.
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Supplementary Information
1
Supplementary information (copies of H NMR,
13C NMR and EI-MS of synthesized compounds (3a-3d
and 5a-5d) and DFT calculation information) is available
free of charge at http://jbcs.sbq.org.br as PDF file.
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1997, 1, 149; Saeidian, H.; Sadeghi, A.; Mirjafary, Z.;
Moghaddam, F. M.; Synth. Commun. 2008, 38, 2043; Blass,
B. E.; Tetrahedron 2002, 58, 9301; Yadav, V. K.; Babu, K. G.;
Mittal, M.; Tetrahedron Lett. 2001, 57, 7047; Moghaddam,
F. M.; Saeidian, H.; Mirgafary, Z.; Sadeghi, A.; Lett. Org.
Chem. 2007, 8, 576; Nazari, M.; Movassagh, B.; Tetrahedron
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Acknowledgements
We would like to acknowledge the financial support
from Payame Noor University (PNU). We also are very
grateful to Dr Zandi for his valuable suggestions on this
paper to reach reasonable conclusions.
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Submitted: March 12, 2014
Published online: May 16, 2014

J. Braz. Chem. Soc., Vol. 25, No. 7, S1-S18, 2014.
Printed in Brazil - ©2014 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Supplementary Information
SI
Efficient Synthesis of Novel Pyranoquinoline Derivatives from Simple Acetanilide
Derivatives: Experimental and Theoretical Study of their Physicochemical
Properties using DFT Calculations
Zohreh Mirjafary,a Hamid Saidian,*,b Morteza Sahandib and Leila Shojaeib
aDepartment of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran
bDepartment of Science, Payame Noor University (PNU), PO Box 19395-4697, Tehran, Iran
Figure S1. 1H NMR of spectrum 3a (CDCl3, 500 MHz).
*e-mail: h_porkaleh@yahoo.com

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Efficient Synthesis of Novel Pyranoquinoline Derivatives from Simple Acetanilide Derivatives
J. Braz. Chem. Soc.
Figure S2. 1H NMR spectrum of 3a (CDCl3, 500 MHz).
Figure S3. 13C NMR spectrum of 3a (CDCl3, 125 MHz).

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Figure S4. 13C NMR spectrum of 3a (CDCl3, 125 MHz).
Figure S5. 1H NMR spectrum of 3b (CDCl3, 500 MHz).

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Efficient Synthesis of Novel Pyranoquinoline Derivatives from Simple Acetanilide Derivatives
J. Braz. Chem. Soc.
Figure S6. 1H NMR spectrum of 3c (CDCl3, 500 MHz).
Figure S7. 1H NMR spectrum of 3d (CDCl3, 500 MHz).

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Figure S8. 1H NMR spectrum of 4a (CDCl3, 500 MHz).
Figure S9. 1H NMR spectrum of 4a (CDCl3, 500 MHz).

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Efficient Synthesis of Novel Pyranoquinoline Derivatives from Simple Acetanilide Derivatives
J. Braz. Chem. Soc.
Figure S10. 1H NMR spectrum of 4a (CDCl3, 500 MHz).
Figure S11. 13C NMR spectrum of 4a (CDCl3, 125 MHz).

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Figure S12. 13C NMR spectrum of 4a (CDCl3, 125 MHz).
Figure S13. 13C NMR (DEPT 135) spectrum of 4a (CDCl3, 125 MHz).

S8
Efficient Synthesis of Novel Pyranoquinoline Derivatives from Simple Acetanilide Derivatives
J. Braz. Chem. Soc.
Figure S14. EI-MS spectrum of 4a.
Figure S15. 1H NMR spectrum of 4b (CDCl3, 400 MHz).

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Figure S16. 1H NMR spectrum of 4b (CDCl3, 400 MHz).
Figure S17. 13C NMR spectrum of 4b (CDCl3, 100 MHz).

S10
Efficient Synthesis of Novel Pyranoquinoline Derivatives from Simple Acetanilide Derivatives
J. Braz. Chem. Soc.
Figure S18. 13C NMR spectrum of 4b (CDCl3, 100 MHz).
Figure S19. EI-MS spectrum of 4b.

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Figure S20. 1H NMR spectrum of 4c (CDCl3, 400 MHz).
Figure S21. 1H NMR spectrum of 4c (CDCl3, 400 MHz).

S12
Efficient Synthesis of Novel Pyranoquinoline Derivatives from Simple Acetanilide Derivatives
J. Braz. Chem. Soc.
Figure S22. 13C NMR spectrum of 4c (CDCl3, 100 MHz).
Figure S23. 13C NMR spectrum of 4c (CDCl3, 100 MHz).

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Figure S24. EI-MS spectrum of 4c.
Figure S25. 1H NMR spectrum of 4d (CDCl3, 400 MHz).

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Efficient Synthesis of Novel Pyranoquinoline Derivatives from Simple Acetanilide Derivatives
J. Braz. Chem. Soc.
Figure S26. 1H NMR spectrum of 4d (CDCl3, 400 MHz).
Figure S27. 13C NMR spectrum of 4d (CDCl3, 100 MHz).

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Figure S28. 13C NMR spectrum of 4d (CDCl3, 100 MHz).
Figure S29. EI-MS spectrum of 4d.

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Efficient Synthesis of Novel Pyranoquinoline Derivatives from Simple Acetanilide Derivatives
J. Braz. Chem. Soc.
Table S1. Symbolic Z-matrix: charge = 0, multiplicity = 1
C
C
C
C
C
C
H
H
C
H
H
C
C
H
N
C
C
C
O
C
C
H
H
C
C
H
O
C
H
H
H
C
H
H
H
H
5.58978
4.33858
3.18587
3.34039
4.64035
5.74518
6.46684
4.20461
2.16352
4.75061
6.73674
0.92876
0.90737
2.23179
1.95798
−0.32426
−1.48604
−1.49516
−0.28019
−2.8002
-3.98094
−4.89626
−3.91871
−3.99208
−2.61332
−2.52504
−2.89644
−4.99623
−4.70869
−5.0479
−5.99685
−4.42511
−3.76322
−5.44168
−4.40191
−0.34212
−1.00942
−1.57814
−0.76528
0.65245
1.20702
0.39132
−1.64214
−2.6495
1.43239
2.28298
0.8196
0.03819
−0.01819
−0.02234
0.03151
0.08847
0.09207
0.04155
−0.0592
0.0218
Figure S30. Atom numbering in accordance with molecular structure of
pyranoquinoline 5a.
0.12902
0.13609
−0.03219
-0.07651
0.05578
−0.07596
−0.06117
−0.10623
−0.09691
−0.12881
−0.17138
−0.56567
−0.34296
−1.65479
0.06103
−0.02363
0.02598
0.02855
−0.7036
−1.74999
−0.26455
−0.66713
1.54333
2.1119
0.82828
−0.60511
2.51264
−1.36227
1.53273
0.84859
−0.60227
−1.27097
1.55224
0.6916
1.2378
0.58645
−0.72161
−1.33544
−2.41288
2.7466
−1.60222
−1.70921
−2.59967
−1.16871
−0.63359
0.02019
−0.24399
−1.61836
2.6144
Figure S31. Correlation coefficient for 1H NMR chemical shifts in GIAO
and CSGT methods for pyranoquinoline 5a.
1.62466
2.01084
−0.0548
Figure S32. NMR calculations with molecular structure of pyranoquinoline
5a.

Vol. 25, No. 7, 2014
Mirjafary et al.
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1
Table S2. Computed B3LYP/6-31+G(d,p) H and 13C NMR chemical
Table S3. Computed B3LYP/6-31+G(d,p) 1H and 13C NMR chemical
shifts for pyranoquinoline 5a relative to TMS
shifts (ppm) for pyranoquinoline 5a and TMS
Pyranoquinoline 5a
TMS
Chemical shifts / ppm
Atom
Atom
GIAO
65.5686
66.0551
46.5088
66.6606
68.7895
71.4025
59.9738
69.4734
37.4360
70.7957
66.0421
45.4116
0.5899
CSGT
63.0161
63.6816
43.6895
64.7685
65.5050
68.8041
55.7594
73.4249
34.1288
65.3104
63.8793
41.1712
-1.0235
138.5408
159.3515
77.2708
161.6168
163.0471
23.5501
23.3384
23.6613
23.8558
23.7225
28.2171
28.2756
25.4430
28.9536
28.8072
28.9489
28.9604
29.1500
28.9178
24.3643
GIAO
CSGT
GIAO
125.80
125.31
144.85
124.70
122.57
119.96
131.39
121.89
153.93
120.57
125.32
145.95
190.77
53.54
36.46
111.81
30.65
29.01
7.84
CSGT
130.75
130.08
150.07
128.99
128.26
124.96
138.00
120.34
159.63
128.45
129.88
152.59
194.79
55.22
34.41
116.49
32.15
30.72
5.88
C1
191.3637
191.3637
191.3637
191.3637
191.3637
191.3637
191.3637
191.3637
191.3637
191.3637
191.3637
191.3637
191.3637
191.3637
191.3637
191.3637
191.3637
191.3637
31.6210
31.6210
31.6210
31.6210
31.6210
31.6210
31.6210
31.6210
31.6210
31.6210
31.6210
31.6210
31.6210
31.6210
31.6210
193.7630
193.7630
193.7630
193.7630
193.7630
193.7630
193.7630
193.7630
193.7630
193.7630
193.7630
193.7630
193.7630
193.7630
193.7630
193.7630
193.7630
193.7630
29.4288
29.4288
29.4288
29.4288
29.4288
29.4288
29.4288
29.4288
29.4288
29.4288
29.4288
29.4288
29.4288
29.4288
29.4288
C1
C2
C2
C3
C3
C4
C4
C5
C5
C6
C6
C9
C9
C12
C13
C16
C17
C18
C20
C21
C24
C25
C28
C32
H7
C12
C13
C16
C17
C18
C20
C21
C24
C25
C28
C32
H7
137.8278
154.9028
79.5548
160.7181
162.3555
23.7831
23.7009
24.0046
24.1978
24.0849
29.3568
29.3125
26.0548
30.4356
30.4231
30.6055
30.5519
30.5932
30.5309
24.4410
H8
H8
7.92
6.09
H10
H11
H14
H22
H23
H26
H29
H30
H31
H33
H34
H35
H36
H10
H11
H14
H22
H23
H26
H29
H30
H31
H33
H34
H35
H36
7.62
5.77
7.42
5.57
7.54
5.71
2.26
1.21
2.31
1.15
5.57
3.99
1.19
0.48
1.20
0.62
1.02
0.48
1.07
0.47
1.03
0.28
1.09
0.51
7.18
5.06

S18
Efficient Synthesis of Novel Pyranoquinoline Derivatives from Simple Acetanilide Derivatives
J. Braz. Chem. Soc.
Table S4. # B3LYP/6-31+G** NMR, Symbolic Z-matrix: charge = 0,
multiplicity = 1 for 4c
C
C
−4.27896
−4.03364
−2.73505
−1.64273
−1.90796
−3.24821
−0.37312
0.62226
0.49238
−0.78999
1.85726
1.69403
−6.08609
2.9084
−0.14203
−1.53332
−1.99991
−1.09916
0.30717
0.77089
−1.60563
−0.76666
0.66581
1.1788
−0.01106
−0.05842
−0.09396
−0.08352
−0.03557
0.00051
−0.11793
−0.1049
−0.06338
−0.02878
−0.14032
−0.07854
0.03666
−0.11168
−0.098
C
C
C
C
N
C
C
C
O
C
−1.34361
1.46409
0.46693
0.86213
−0.58869
−1.24284
−0.52397
0.88591
1.65975
−1.33045
2.86742
−0.39816
−2.22587
−3.06295
1.83686
2.25508
2.54856
−2.32839
1.50093
0.7731
Br
C
C
3.02388
4.19712
5.52774
5.41827
4.17154
6.6087
C
−0.0159
0.08506
−0.5494
−0.16864
−0.66321
0.02322
1.5766
C
C
C
C
O
C
4.17682
5.93189
−4.86799
−2.52157
−3.4478
−0.94079
1.63219
4.18774
6.29258
5.37583
7.57637
6.34311
6.7325
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Bq
Bq
Bq
Bq
Bq
−0.06623
−0.13026
0.03697
0.00216
−0.07536
0.03318
−0.31809
−1.64355
−0.61685
−1.717
−0.81828
−1.46671
−2.32245
0.0704
−0.21452
1.67024
2.04927
2.13589
−0.04387
0.45275
0.95275
1.45275
1.95275
6.91875
5.97685
5.21143
−2.96439
−2.9761
−2.9761
−2.9761
−2.9761
−1.38487
0.2079
−0.57828
−0.63509
−0.63509
−0.63509
−0.63509