The synthesis, characterization and optical properties of novel 2-Acyl 6-Arylindolizines

Article abstract of DOI:10.1016/j.saa.2014.06.146

A series of novel 2-Acyl-6-Aryl substituted indolizine derivatives was synthesized by a novel tandem reaction between 4-Acyl-pyrrole-2-carbaldehyde derivatives and ethyl 4-bromo-3-Arylbut-2-enoate under mild conditions. The compounds were characterized using IR, ¹H NMR ¹³C NMR and HRMS. The crystal structure of 7a was determined using single crystal X-ray crystallography. The absorption results showed that compounds 7a-e presented their absorption maxima at ca. 270 nm, while compounds 7f and 7g with a larger conjugation system exhibited red-shifted absorption character (ca. 280 nm). Fluorescence spectra revealed that these compounds exhibited blue fluorescence (434-456 nm) in dilute solutions and showed quantum yields of fluorescence between 0.02 and 0.39 in dichloromethane.

Full text of DOI:10.1016/j.saa.2014.06.146

Accepted Manuscript
The synthesis, characterization and optical properties of novel 2-acyl 6-arylin-
dolizines
Yan Qing Ge, Xue Yong Gong, Guang Jie Song, Xiao Qun Cao, Jian Wu Wang
PII:
S1386-1425(14)01045-2
http://dx.doi.org/10.1016/j.saa.2014.06.146
SAA 12405
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Reference:
Spectrochimica Acta Part A: Molecular and Biomo-
lecular Spectroscopy
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7 April 2014
6 June 2014
29 June 2014
Please cite this article as: Y.Q. Ge, X.Y. Gong, G.J. Song, X.Q. Cao, J.W. Wang, The synthesis, characterization
and optical properties of novel 2-acyl 6-arylindolizines, Spectrochimica Acta Part A: Molecular and Biomolecular
Spectroscopy (2014), doi: http://dx.doi.org/10.1016/j.saa.2014.06.146
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The synthesis, characterization and optical properties of novel 2-acyl
6-arylindolizines
Yan Qing Gea, Xue Yong Gonga, Guang Jie Songa, Xiao Qun Caoa*, Jian Wu Wang b*
aSchool of Chemical Engineering, Taishan Medical University, Taian, Shandong,
271016, PR China.
bSchool of Chemistry and Chemical Engineering, Shandong University, Jinan,
Shandong, 250100, PR China.
*Corresponding author. Tel.: +86 538 6236195, fax: +86 538 6229741,
E-mail: xqcao@tsmc.edu.cn(Xiao Qun Cao); jwwang@sdu.edu.cn(Jian Wu Wang).
1

Abstract
A series of novel 2-acyl-6-aryl substituted indolizine derivatives was synthesized by a
novel tandem reaction between 4-acyl-pyrrole-2-carbaldehyde derivatives and ethyl
4-bromo-3-arylbut-2-enoate under mild conditions. The compounds were
1
characterised using IR, H NMR 13C NMR and HRMS. The crystal structure of 7a
was determined using single crystal X-ray crystallography. The absorption results
showed that compounds 7a-e presented their absorption maxima at ca. 270 nm, while
compounds 7f and 7g with a larger conjugation system exhibited red-shifted
absorption character (ca. 280 nm). Fluorescence spectra revealed that these
compounds exhibited blue fluorescence (434-456 nm) in dilute solutions and showed
quantum yields of fluorescence between 0.02 and 0.39 in dichloromethane.
Key words: Synthesis, Tandem, Indolizine, Nitrogen-bridgehead, UV absorption,
Fluorescence
1. Introduction
Nitrogen-bridgehead heterocycles have attracted considerable attention from
medicinal and organic chemists due to their wide variety of biological activities and
optical/electrical properties, and many of attractive methods have been developed for
synthesizing this class of compounds. Of these heterocycles, indolizines play
important roles as calcium entry blockers[1], potential central nervous system
depressants[2], 5-HT3 receptor antagonist[3], histamine H3 receptor antagonists[4],
cardiovascular agents[5], and PLA2 inhibitors[6].
The indolizine ring has a large dipole moment due to the non-uniform charge
2

distribution in the five-membered and six-membered rings (Fig. 1). Within the
indolizine ring, electronic charge builds up significantly in the five-membered ring
while low electron density appears in the six-membered ring. Conjugated organic
compounds with large polarizabilities are of particular use in the field of optical
electronics, such as non-linear optics [7]. To date little attention has been paid to the
photophysical properties of these indolizine derivatives[8-12]. Continuing our efforts
on extending the scope and applications of the tandem reaction for the preparation of
nitrogen-bridgehead heteroaromatics [13-15] and in order to search for novel
fluorescent organic compounds with potential bioactivities[16-22], herein,
2-acyl-6-arylindolizines were conveniently synthesized by a novel tandem reaction
under mild conditions and their structure and optical properties were described.
Fig. 1
2. Experimental
2.1. General
All reagents were commercially available and used without further purification.
Melting points were determined on an XD-4 digital micro melting point apparatus. 1H
NMR spectra were recorded on a Bruker Avance 300 (300 MHz) spectrometer, using
CDCl3 as solvent and tetramethylsilane (TMS) as internal standard. IR spectra were
recorded with an IR spectrophotometer VERTEX 70 FT-IR (Bruker Optics). HRMS
spectra were recorded on a Q-TOF6510 spectrograph (Agilent). UV-vis spectra were
recorded on a U-4100 (Hitachi). Fluorescent measurements were recorded on a
Perkin-Elmer LS-55 luminescence spectrophotometer.
3

2.2. Synthesis
2.2.1 General procedure for the preparation of 3
As shown in Fig. 2, compounds 3 were synthesized according to the literature
method [23]. To a suspension of sodium hydride (0.24 g, 10mmol) in dry THF
(100mL) was added dropwise triethyl phosphonoacetate (2.34 g, 10mmol) at 0°C
under nitrogen atmosphere. The mixture was stirred for 1 h at 0 °C and then the
appropriate ketone (6.76mmol) in 15mL THF was added dropwise. After stirring at
room temperature for 2 days and then cooled with a water bath, a saturated aqueous
ammonium chloride solution (20mL) was added dropwise to the cold mixture. The
aqueous phase was extracted with ethyl acetate (3 × 40mL) and the combined organic
phase was washed with brine (3 × 30mL), dried over sodium sulphate and
concentrated under reduced pressure. The crude residue was purified by column
chromatography on silica gel to afford compounds 3 in 70–85% yield.
Fig.2
2.2.2 General procedure for the preparation of 6
Compounds 6 were synthesized according to the literature method [14].
2.2.3 General procedure for the preparation of 7a-g and 8
To a 50-mL round-bottomed flask were added 6 (1.00 mmol), an α, β-unsaturated
esters 3 (1.20 mmol), potassium carbonate (0.28 g, 2.05 mmol) and dry DMF (10 mL).
The mixture was stirred at 50 °C for 8-12 h and then filtered. The filtrate was poured
into water (100 mL) and extracted with CH2Cl2 (3 × 30 mL). The combined extracts
were washed with water, dried over anhydrous MgSO4 and filtered, and the solvent
4

was removed by rotary evaporation. The crude products were purified by column
chromatography to afford compound 7a-g and 8 in 42-68%.
2.2.3.1 ethyl 2-acetyl-6-phenylindolizine-7-carboxylate (7a).
1
Yellow solid (62% yield): mp 110.4-111.6 °C; H NMR (300 MHz, CDCl3): δ =
8.10 (s, 1H), 7.85 (d, J = 0.9 Hz, 1H), 7.77 (s, 1H), 7.41-7.28 (m, 5H), 7.05 (s, 1H),
13
4.09 (q, J = 7.2 Hz, 2H), 2.56 (s, 3H), 1.03 (t, J = 7.2 Hz, 3H); C NMR (100 MHz,
CDCl3): δ = 194.5, 166.4, 138.0, 131.0, 130.1, 128.6, 128.0, 127.5, 126.8, 125.0,
124.7,122.6, 116.8, 103.9, 61.0, 27.7, 13.7; IR (KBr) ν = 3126, 3062, 2983, 2904,
1737, 1700, 1669, 1627, 1483, 1400, 1273, 1091cm−1; HRMS: m/z calcd for
C19H18NO3 [M+H]+ 308.1287, found 308.1282.
2.2.3.2 ethyl 2-acetyl-6-(4-methoxyphenyl)indolizine-7-carboxylate (7b).
Yellow solid (55% yield): mp 182.8-185.7 °C; 1H NMR (300 MHz, CDCl3): δ =
8.09 (s, 1H), 7.83 (d, J = 0.9 Hz, 1H), 7.75 (s, 1H), 7.23 (d, J = 9.0 Hz, 2H), 7.04 (s,
1H), 6.93 (d, J = 9.0 Hz, 2H), 4.12 (q, J = 7.2 Hz, 2H), 3.84 (s, 3H), 2.57 (s, 3H), 1.10
(t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 194.5, 166.4, 159.2, 131.0,
130.2, 130.0, 129.7, 126.5, 124.8, 124.6, 122.7, 116.6, 113.5, 103.9, 61.0, 55.3, 27.7,
13.9; IR (KBr) ν = 3127, 3064, 2982, 2902, 1700, 1667, 1627, 1486, 1405, 1270,
1091cm−1; HRMS: m/z calcd for C20H20NO4 [M+H]+ 338.1392, found 338.1396.
2.2.3.3 ethyl 2-acetyl-6-(4-chlorophenyl)indolizine-7-carboxylate(7c).
Yellow solid (68% yield): mp 184.6-185.9 °C; 1H NMR (300 MHz, CDCl3): δ =
8.16 (s, 1H), 7.86 (d, J = 0.9 Hz, 1H), 7.75 (s, 1H), 7.37 (d, J = 8.4 Hz, 2H), 7.24 (d, J
= 8.4 Hz, 2H), 7.08 (s, 1H), 4.13 (q, J = 7.2 Hz, 2H), 2.58 (s, 3H), 1.11 (t, J = 7.2 Hz,
5

3H); 13C NMR (100 MHz, CDCl3): δ = 194.4, 166.0, 136.5, 133.6, 131.1, 130.3,
130.0, 128.2, 125.8, 125.1, 125.0, 121.9, 116.9, 104.3, 61.1, 27.8, 13.9; IR (KBr) ν =
3128, 3055, 2983, 2913, 1699, 1671, 1628, 1484, 1402, 1279, 1093cm−1cm−1; HRMS:
m/z calcd for C19H17ClNO3 [M+H]+ 342.0897, found 342.0899.
2.2.3.4 ethyl 2-acetyl-6-(naphthalen-2-yl)indolizine-7-carboxylate (7d).
Yellow solid (45% yield): mp 124.6-126.8 °C; 1H NMR (300 MHz, CDCl3): δ =
8.28 (s, 1H), 7.88-7.83 (m, 4H), 7.59-7.34 (m, 5H), 7.14 (s, 1H), 3.75 (q, J = 7.2 Hz,
2H), 2.58 (s, 3H), 0.54 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 194.5,
165.7, 136.1, 133.2, 133.1, 131.4, 130.2, 128.3, 18.1, 126.6, 126.3, 125.8, 125.6,
125.3, 125.2, 124.9, 123.2, 116.9, 104.4, 60.6, 27.8, 13.1; IR (KBr) ν = 3128, 3056,
2977, 2902, 1700, 1677, 1622, 1479, 1398, 1269, 1183, 1078cm−1; HRMS: m/z calcd
for C23H20NO3 [M+H]+ 358.1443, found 358.1440.
2.2.3.5 ethyl 2-acetyl-6-(thiophen-2-yl)indolizine-7-carboxylate (7e).
Yellow solid (42% yield): mp 110.8-112.5 °C; 1H NMR (300 MHz, CDCl3): δ =
8.07 (s, 1H), 7.92 (s, 1H), 7.85 (d, J = 0.9 Hz, 1H), 7.34 (dd, J = 1.2, 4.8 Hz, 1H),
7.07-7.01 (m, 3H), 4.17 (q, J = 7.2 Hz, 2H), 2.57 (s, 3H), 1.15 (t, J = 7.2 Hz, 3H); 13C
NMR (100 MHz, CDCl3): δ = 194.4, 166.0, 138.6, 131.0, 130.3, 127.1, 126.9, 1225.9,
125.7, 124.4,122.9, 119.3, 116.8, 104.2, 61.4, 27.8, 13.8; IR (KBr) ν = 3125, 3075,
2978, 2905, 1704, 1667, 1627, 1482, 1397, 1271, 1086cm−1; HRMS: m/z calcd for
C17H16NO3S [M+H]+ 314.0851, found 314.0856.
2.2.3.6 ethyl 2-benzoyl-6-(4-chlorophenyl)indolizine-7-carboxylate (7f).
1
Yellow solid (60% yield): mp 97.2-103.7 °C; H NMR (300 MHz, CDCl3): δ =
6

8.19 (s, 1H), 7.94-7.91 (m, 2H), 7.87 (s, 1H), 7.77 (s, 1H), 7.63-7.49 (m, 3H), 7.38 (d,
J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H),7.14 (s, 1H), 4.14 (q, J = 7.2 Hz, 2H), 1.12 (t,
J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 191.3, 166.0, 139.0, 138.6, 132.2,
130.8, 129.4, 129.0, 128.4, 127.1, 126.9, 125.9, 125.7, 124.4, 122.9, 119.3, 118.6,
61.1, 13.9; IR (KBr) ν = 3115, 3076, 2981, 1708, 1631, 1478, 1394, 1265, 1120cm−1;
HRMS: m/z calcd for C24H19ClNO3 [M+H]+ 404.1053, found 404.1055.
2.2.3.7 ethyl 2-benzoyl-6-(thiophen-2-yl)indolizine-7-carboxylate (7g).
Yellow solid (45% yield): mp 131.8-133.4 °C; 1H NMR (300 MHz, CDCl3): δ =
8.10 (s, 1H), 7.94-7.91 (m, 3H), 7.84 (d, J = 0.9 Hz, 1H), 7.63-7.48 (m, 3H),
7.36-7.34 (dd, J = 1.6, 5.1 Hz, 1H), 7.12 (s, 1H), 7.07-7.00 (m, 2H), 4.18 (q, J = 7.2
Hz, 2H), 2.57 (s, 3H), 1.14 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ =
191.3, 166.0, 139.0, 136.6, 133.6, 132.2, 130.8, 129.4, 130.0, 129.4, 129.0, 128.4,
128.2, 125.8, 125.1, 125.0, 121.9, 118.6, 61.1, 13.9; IR (KBr) ν = 3124, 3054, 2979,
1721, 1641, 1462, 1271, 1086cm−1; HRMS: m/z calcd for C22H18NO3S [M+H]+
376.1007, found 376.1001.
2.2.3.8 ethyl 4-(4-acetyl-2-formyl-1H-pyrrol-1-yl)-3-(thiophen-2-yl)but-2-enoate (8).
1
Yellow solid (65% yield): H NMR (300 MHz, CDCl3): δ 9.66 (d, J = 0.9 Hz,
1H), 7.56 (s, 1H), 7.30 (m, 2H), 7.24 (m, 1H), 6.97 (m, 1H), 6.51 (s, 1H), 6.13 (s, 2H),
4.25 (q, J = 7.2 Hz, 2H), 2.37 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H).
2.3. X-ray crystallography
Single crystals of compound 7a suitable for X-ray diffraction were obtained by
slow evaporation of a solution of the solid in ethyl acetate at room temperature for 2
7

days. A crystal with approximate dimension of 0.28 mm × 0.24 mm × 0.21 mm was
mounted on a Bruker Smart Apex II CCD equipped with a graphite monochromated
MoKα radiation (λ= 0.71073Å) by using Φ and ω scan modes and the data were
collected at 293(2) K. The structure of the crystal was solved by direct methods and
refined by full-matrix least-squares techniques implemented in the SHELXTL-97
crystallographic software. The non-hydrogen atoms were refined anisotropic ally. The
hydrogen atoms bound to carbon were located by geometrical calculations, with their
position and thermal parameters being fixed during the structure refinement. A
summary of the crystallographic data and structure refinement details is given in
Table 1, and the selected bond lengths and angles are presented in Table 2. The crystal
structure and cell structure of 7a are shown in Figs. 3 and 4, respectively.
Table 1 and Table 2
Fig. 3 and Fig. 4
3. Results and discussion
3.1 Synthesis
The desired indolizines 7 were obtained by the reactions of compounds 6 and the
bromoaryl substituted esters 3 in the presence of K2CO3. It is noted that the presence
of a benzoyl or acetyl substituent of pyrrole did not show any significant influence on
the outcome of the reaction but the presence of an aryl substituent on the α,
β-unsaturated ester interfered with the reaction because of the electric effect.
Increased temperature (50 °C) and extended reaction time (up to 12 h) was required to
obtain the desired product compared with the previous report[14]. Additionally, we
8

obtained the intermediate ethyl 4-(4-acetyl-2-formyl-1H-pyrrol-1-yl)-3-(thiophen-2-
yl)but-2-enoate 8 under room temperature. On the basis of the above results and our
previous work [13-16], we believe that this reaction proceeds by an SN2 displacement
of bromide ion, deprotonation resulting in an ester stabilised anion which facilitates
cyclisation and a subsequent dehydration as shown in Fig. 5.
Fig. 5
3.2. Structure characterization
The structures of products 7a-g were characterized by spectroscopic methods (1H
NMR, 13C NMR, IR and HRMS). For example, compound 7a, obtained as yellow
crystals, gave a [M + H]-ion peak at m/z 308.1282 in the HRMS, in accord with the
molecular formula C19H18NO3. The IR spectra showed the characteristic absorption
bands at 3062 (Ar-H), 2983(CH3), 2904(CH2), 1700 (C=O), 1669 (C=N), 1627
(C=C), 1273 (C-O-C) and the 1H NMR spectra (CDCl3) revealed five distinct singlets
at δ 2.56 (3H, -COCH3), 2.42 (3H, CH3), 2.47 (3H, CH3), 7.05 (1H, pyrrole moiety),
7.77 (1H, pyrrole moiety) and 8.10 (1H, pyridine moiety). Moreover, compound 7a
showed peaks at δ 1.03 (t, 3H, J = 7.2 Hz), 4.09 (q, 2H, J = 7.2 Hz), assigned to the
protons of ethoxycarbonyl group. All other signals are consistent with the structure of
7a.
3.3. Crystal structure
The crystal structure of 7a is in a triclinic system with a P-1 space group. The
indolizine subunit is substantially planar with a dihedral angle of 1.47° between
pyrrole and pyridine segments. The dihedral angle between the indolizine ring and
9

phenyl ring is 55.21°. Selected bond lengths and bond angles are listed in Table 2. The
results reveal that the carbon-carbon bond lengths on the molecular skeleton are
basically intermediate between typical C-C single (1.54 Å) and C-C double (1.34 Å)
bonds. The carbon-nitrogen bond lengths are also intermediate between typical C-N
single (1.47 Å) and C=N double (1.27 Å) bonds. This indicates that the π-electrons in
the molecule are delocalized.
3.4. Absorption spectral characteristics of the compounds 7a-g
For UV-visible absorption measurements, the dye concentration was 1×10-5 mol
L-1, and the UV-visible absorption spectra of compounds 7a-g are given in Fig. 6. The
absorption data are summarized in Table 3. Several absorption peaks could be
observed in the wavelength range from 230 to 420 nm, while almost no absorption
was observed beyond 425 nm. It is noted that 7a-g display very similar absorptions
with a strong absorption band at ca. 270 nm, which should originate from the benzene
ring and indolizine ring and should be assigned to the π-π* electronic transition. The
relatively weak absorption bands between 300 and 420 nm are assigned to the n-π*
electronic transition.
The data indicated that the structure of 6-aryl group only slightly affects the
absorption bands while 2-acyl group obviously affects the absorption. Compounds 7a,
7b, 7c and 7e demonstrate similar absorption properties, with absorption peaks at 269
nm, 266 nm, 272 nm and 267 nm, respectively. The result reveals that 6-phenyl ring,
substituent groups (OCH3, Cl) on 6-phenyl ring or 6-thiophenyl ring slightly affect the
absorption character of these compounds. As the steric hindrance of the 6-aryl ring
10

increased, the maximum absorption of compound 7d with the 2-naphthyl ring is
blue-shifted to 261nm compared to compound 7a, which indicates that the conjugated
π-system between the 6-aryl ring and indolizine ring decreases due to steric hindrance
effect. Comparing with 7c and 7e the absorption maxima of compounds 7f and 7g, in
which a benzoyl group is bonded to the C-2 position of indolizine ring, are red shifted
7 nm and 13 nm, respectively. The difference in absorption spectra is due to the fact
that the phenyl group enhances the extent of conjugation in compounds 7f and 7g.
Influence of solvent on the absorption behavior was investigated. The absorption
spectra of 7a, as an example, in three different solvents (cyclohexane,
dichloromethane and acetonitrile) at a concentration of 1 × 10-5 mol L-1 are shown in
Fig. 7. It is observed that the absorption spectra change slightly with the increase of
solvent polarity although there is a tendency of a shorter λmax in acetonitrile,
indicating that there is no charge transfer in the ground state.
Table 3
Fig. 6 and Fig. 7
3.5. Fluorescence spectral characteristics
The emission spectra of compounds 7a-g in dichloromethane solution (1× 10-6
mol L-1) are presented in Fig. 8 and the data were summaries in Table 3. They present
efficient blue emissions in dilute solution, with maximum emission spectra ranging
from 434 to 456 nm. The fluorescence maximum emission bands of 7a-g are
dependent on the groups bonded to indolizine rings. The emission maxima of 7b, 7c,
7d and 7e, in which -OCH3Ph, -ClPh, thiophenyl and naphthalenyl are bonded to the
11

C-6 position of indolizine ring, are red-shifted by 12, 11, 10 and 12 nm, respectively,
compared to 7a. The emission maxima of 7f and 7g, in which benzoyl bonded to the
C-2 position of indolizine ring, are red-shifted by 9 and 10 nm, respectively,
compared to 7c and 7e. Those rusults might be attributed to the different conjugation
degree and different electronic effects in these compounds.
Fig. 8
It can also be found that their intensity of fluorescence differed from each other.
The fluorescence intensity of compounds 7e-g are extremely weak compared with
other compounds, which may be due to the interaction of molecules leading to the
quenching of fluorescence at the measured concentration of 1× 10-6 mol L-1. For
compound 7g, the Donor-Acceptor structure character resulting from the
electrondonating thiophenyl group and electron-withdrawing benzoyl and ester groups
is in favor of dipole-dipole interactions between molecules.
The Stoke’s shifts range from 165 to 183 nm, indicating the existence of
molecular conformation deviation between the ground state and the exited state.
Fluorescence quantum yields (ΦF) in CH2Cl2 were determined by a comparative
method, using quinine sulfate as standard. The highest ΦF value of 0.39 is observed
for 7a, which is higher than that of other compounds. The fluorescence quantum
yields of the other compounds are in the range of 0.02-0.27. This difference might be
due to the change of the electronic push-pull substitution of the conjugated part in the
molecules.
The solvent effects on the fluorescence characteristics of these compounds were
12

investigated in cyclohexane, CH2Cl2 and CH3CN at the concentration of 1× 10-6 mol
L-1. For compound 7d in Fig. 9, the emission wavelengths are red shifted with the
increase of solvent polarity from 435 nm in cyclohexane to 444 nm in CH2Cl2 and 449
nm in CH3CN. Due to the interaction between fluorescent molecules and solvent, the
fluorescence is enhanced with the decrease of solvent polarity.
Fig. 9
4. Conclusion
This paper describes the use of a novel tandem reaction to prepare indolizine
derivatives under mild conditions in moderate to good yields. The structures of
compounds obtained were determined by IR, 1H NMR, 13C NMR, and HRMS spectra,
and the spatial structure of compound 7a was confirmed by X-ray crystallography.
Absorption and fluorescence spectral characteristics of the compounds were
investigated. Compounds 7f-g show red-shifted absorption peaks compared to the
corresponding absorption of 7a-e, due to their extended conjugation. These
compounds exhibited blue fluorescence (434-456 nm) in dilute solutions and showed
acceptable quantum yields of fluorescence in dichloromethane, with the highest ΦF
value of 0.39 for compound 7a. It can be concluded that the absorption and
fluorescence characteristics of compounds 7a-g show a significant dependence on the
structure of 2-acyl group in the C-2 position of indolizine but slightly on 6-aryl group.
These small molecules have potential bioactivities and their anticancer activities are
currently under investigation.
5. Supplementary materials
13

CCDC 903100 contains the supplementary crystallographic data for this paper.
These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif,
by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge CB21EZ, UK; fax: t44
1223 336033.
Acknowledgement
We thank the Science and Technology Development Project of Shandong
Province (2012GSF11812), the Natural Science Foundation of Shandong Province
(ZR2012BL04 and ZR2013BM020) and the Natural Science Foundation of Taishan
Medical University (2013GCC02) for financial support.
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17

Figure Captions:
Table 1 Crystal data and structure refinement for 7a
Table 2
Table 3
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Selected bond lengths and angles for 7a
The optical characteristics of the compounds 7a-g in dichloromethane.
Charge distribution within indolizine moiety
Synthetic routes of 7a-g.
The molecular structures of 7a.
A packing diagram for 7a.
The mechanism of the tandem reaction.
The UV-vis spectra of the compounds 7a-g in dichloromethane.
UV-vis absorption spectrum of compound 7a in different solvents
The Fluorescence spectra of the compounds 7a-g in dichloromethane.
The fluorescence spectra of compound 7d in different solvents
18

Table 1 Crystal data and structure refinement for 7a
Empirical formula
Formula weight
C18H15NO3
293.31
Temperature
293(2) K
Wavelength
0.71073 Å
Crystal system, space group
Unit cell dimensions
Triclinic, P-1
a = 7.685(8) Å
b = 8.207(8) Å
α= 74.847(16) °
β = 80.330(19) °
c = 15.319(15) Å γ = 65.234(15) °
Vo lu m e
844.9(15) A3
Z
2
Calculated density
Absorption coefficient
F(000)
1.153 Mg/m3
0.079 mm-1
308
Crystal size
θ range for data collection
Limiting indices
0.28 × 0.24 × 0.21 mm
1.38-25.05°
-6 ≤ h ≤9, -9 ≤ k ≤ 9, -13 ≤ l ≤ 18
4238 / 2913 [R(int) = 0.0556]
97.6 %
Semi-empirical from equivalents
0.9836 and 0.9782
Full-matrix least-squares on F2
2913 / 21 / 204
Reflections collected / unique
Completeness to θ = 25.05°
Absorption correction
Max. and min. transmission
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
Final R indices [I > 2σ(I)]
R indices (all data)
Largest diff. peak and hole
1.027
R1 = 0.0668, wR2 = 0.1811
R1 = 0.1119, wR2 = 0.2135
0.381 and -0.407 e. Å-3
19

Table 2 Selected bond lengths and angles for 7a
bond lengths
N(2)-C(4)
C(6)-C(7)
C(9)-C(10)
1.363(4) N(2)-C(5)
1.465(4) C(4)-C(3)
1.373(5) C(6)-C(5)
1.376(4) N(2)-C(9)
1.382(5) C(8)-C(7)
1.359(5)
1.416(4) C(10)-C(3)
1.360(5) C(8)-C(9)
1.429(5)
1.407(5)
bond angles
C(4)-N(2)-C(5)
C(4)-N(2)-C(9)
C(5)-N(2)-C(9)
C(7)-C(8)-C(9)
C(10)-C(9)-C(8)
C(10)-C(9)-N(2)
C(8)-C(9)-N(2)
C(5)-C(6)-C(7)
C(5)-C(6)-C(13)
C(7)-C(6)-C(13)
C(6)-C(5)-N(2)
C(8)-C(7)-C(6)
C(8)-C(7)-C(11)
C(6)-C(7)-C(11)
N(2)-C(4)-C(3)
129.4(3)
108.7(3)
121.8(3)
121.6(3)
135.5(3)
107.6(3)
116.9(3)
117.4(3)
119.1(3)
123.3(3)
121.8(3)
120.4(3)
116.7(3)
122.9(3)
108.6(3)
C(14)-C(13)-C(18)
C(14)-C(13)-C(6)
118.2(3)
120.5(3)
121.4(3)
107.4(3)
107.6(3)
126.6(3)
125.7(3)
121.1(3)
121.1(4)
117.8(3)
120.9(4)
120.7(4)
120.0(4)
121.1(4)
119.1(4)
C(18)-C(13)-C(6)
C(9)-C(10)-C(3)
C(4)-C(3)-C(10)
C(4)-C(3)-C(2)
C(10)-C(3)-C(2)
O(3)-C(2)-C(3)
O(3)-C(2)-C(1)
C(3)-C(2)-C(1)
C(17)-C(18)-C(13)
C(15)-C(14)-C(13)
C(18)-C(17)-C(16)
C(14)-C(15)-C(16)
C(15)-C(16)-C(17)
20

Table 3 The optical characteristics of the compounds 7a-g in dichloromethane.
Compounds
λmax
λex
(nm)
400
400
400
400
400
400
400
εmax
(L mol-1 cm-1)
58500
F
max (nm) Stokes shift
ΦF
(nm)
(nm)
7a
7b
7c
7d
7e
7f
269
434
446
445
444
446
454
456
165
180
173
183
179
175
176
0.39
266
272
261
267
279
280
43700
0.21
68400
0.27
71800
0.14
73200
0.040
0.043
0.019
94900
7g
70300
21

Fig.1 Charge distribution within indolizine moiety
22

Fig.2
Synthetic routes of 7a-g
PO(OMe)2
EtOOC
EtOOC
Br
NBS / CCl4
COOEt
NaH
O
Ar
Ar
Ar
3
2
1
O
CO2Et
Ar
K2CO3
O
N
O
R1
R1
R1
Cl
(COCl)2/DMF
7a-g
N
CHO
N
H
N
H
N
H
AlCl3
Cl
5
4
6
R1 = CH3, Ar =
R1 = CH3, Ar =
7c
7a R1 = CH3, Ar =
7b
Cl
OCH3
S
S
7e R1 = CH3, Ar =
7g R1 = Ph, Ar =
7d R1 = CH3, Ar =
7f R1 = Ph, Ar =
Cl
Fig.2 Synthetic routes of 7a-g
23

Fig.5 The mechanism of the tandem reaction

1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
-0.1
7a
7b
7c
7d
7e
7f
7g
200
250
300
350
400
450
Wavelength/nm
Fig. 6. The UV-vis spectra of the compounds 7a-g in dichloromethane.

0.6
0.5
0.4
0.3
0.2
0.1
0.0
MeCN
DCM
CHEX
200
250
300
350
400
450
wavelength/nm
Fig. 7 UV-vis absorption spectrum of compound 7a in different solvents

1000
800
600
400
200
0
7a
7b
7c
7d
7e
7f
7g
400
420
440
460
480
500
520
540
560
X Axis Title
Fig. 8 The Fluorescence spectra of the compounds 7a-g in dichloromethane.