Pyridinium ylides in the one-pot synthesis of a new quinoline/indolizine hybrid

Article abstract of DOI:10.1515/znb-2015-0118

The reaction of 1-(quinolin-2-ylmethyl)pyridinium ylide with dimethyl acetylenedicarboxylate was investigated. The X-ray crystallographic characterization of the new dimethyl 3-(quinolin-2-yl)indolizine-1,2-dicarboxylate (2) shows the formation of a five-membered ring between the pyridine ring and the methylene group.

Full text of DOI:10.1515/znb-2015-0118

Z. Naturforsch. 2015; 70(12)b: 885–887
Roumaissa Belguedj, Abdelmalek Bouraiou*, Sofiane Bouacida, Hocine Merazig
aPnyd AriisdsaiCnhiibuanmi ylides in the one-pot synthesis of a
new quinoline/indolizine hybrid
DOI 10.1515/znb-2015-0118
2 Results and discussion
Received July 9, 2015; accepted August 6, 2015
Abstract: The reaction of 1-(quinolin-2-ylmethyl)pyridi- 1-(Quinolin-2-ylmethyl)pyridinium iodide (1) undergoes
nium ylide with dimethyl acetylenedicarboxylate was a dehydrohalogenation reaction in the presence of tri-
investigated. The X-ray crystallographic characterization ethylamine in chloroform to give the corresponding
of the new dimethyl 3-(quinolin-2-yl)indolizine-1,2-dicar- pyridinium ylide. The reaction of the latter with DMAD
boxylate (2) shows the formation of a five-membered ring furnished
dimethylꢀ3-(quinolin-2-yl)indolizine-1,2-di-
between the pyridine ring and the methylene group.
carboxylate (2). The structure of which was established
with the help of NMR spectroscopy and a single crystal
X-ray structure determination. This result clearly showed
that, due to the electron-withdrawing ability of the pyri-
dinium moiety, the methylene is acidic, and a 1,3-dipolar
cycloaddition reaction of the in situ-generated ylide with
DMAD took place. Compound 2 results from the oxidative
dehydrogenation (aromatization) of the initially formed
Keywords: crystal structure; 1,3-dipolar cycloaddition;
indolizine; N-pyridinium ylide.
1 Introduction
1,3-Dipolar cycloaddition of N-pyridinium ylides and cycloadduct in air. The intermediates dihydroindolizine
related heteroaromatic ylides [1], e.g. quinolinium or iso- and tetrahydroindolizine were not stable enough to be
quinolinium ylides, with various dipolarophiles is one of isolated (Scheme 1).
the most important methods for the synthesis of various
Compound 1 crystallizes in the monoclinic space
types of indolizine and benzoindolizine [2]. It offers the group P21/c with Z ꢁ=ꢁ 4 (Fig. 1a; Tables 1 and 2). Compound
advantage of removing a few reaction steps [3] and a 2 crystallizes in the orthorhombic system, space group
simple work-up to reach the target molecule [4]. In contin- P21ab with Z ꢁ=ꢁ 4 (Fig. 1b; Tables 1 and 2). The indolizine
uation of our research interest in heteroaromatic N-ylide ring is close to planar with a maximum deviation of
involving multi-component reactions [5, 6], we report –0.044(3) Å at atom C(16). The quinoline ring is almost
here on the synthesis and the crystal structure determi- planar, with a maximum deviation of –0.020(2) Å at atom
nation of a new quinoline/indolizine hybrid obtained via C(5) and –0.023(2) Å at C(9) and C(4) for both compounds 1
the 1,3-dipolar cycloaddition reaction of dimethyl acety- and 2, respectively. The carboxyl group (C(20)/O(3)–O(4)),
lenedicarboxylate (DMAD) with 1-(quinolin-2-ylmethyl) attached to C(12), forms a dihedral angle of 10.2(1)° with
pyridinium ylide. The crystal structure of the latter as its the plane defined by N(2) and atoms C(10)–C(13), while
iodide salt was also determined.
the second carboxyl group (C(18)/O(1)–O(2)) attached at
C(11) is rotated by 67.54(8)° out of the same plane. Bond
lengths and angles are in the expected range [7, 8]. The
C–N bonds (N(2)–C(13) 1.392(2), N(2)–C(10) 1.3967(19),
N(2)–C(17) 1.380(2) Å) in compound 2 indicate partial
double bond character (Table 2).
*Corresponding author: Abdelmalek Bouraiou, Unité de Recherche
de Chimie de l’Environnement et Moléculaire Structurale, Université
des Frères Mentouri, Constantine 25000, Algeria,
Fax: +213-31-81-88-16, E-mail: bouraiou.abdelmalek@yahoo.fr
Roumaissa Belguedj, Hocine Merazig and Aissa Chibani: Unité de
Recherche de Chimie de l’Environnement et Moléculaire Structurale,
Université des Frères Mentouri, Constantine 25000, Algeria
Sofiane Bouacida: Unité de Recherche de Chimie de
l’Environnement et Moléculaire Structurale, Université des Frères
Mentouri, Constantine 25000, Algeria; and Département sciences
de la matière, Université Oum El Bouaghi, Oum El Bouaghi 04000,
Algeria
3 Conclusion
In summary, the 1,3-dipolar cycloaddition reaction of
1-(quinolin-2-ylmethyl)pyridinium ylide with DMAD as
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ꢀꢀꢀꢁ
886ꢀ ꢀR. Belguedj et al.: Synthesis of a new quinoline/indolizine hybrid
Table 1:ꢀCrystal structure data for 1 and 2.
I
I2
+
ꢁ
1
ꢁ
2
N
120 °C
N
N
N
Formula
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
C15H13N2I
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
C21H16N2O4
360.36
0.16 ꢃ×ꢃ 0.11 ꢃ×ꢃ 0.05
Orthorhombic
P21ab
7.6165(2)
10.9576(2)
20.7831(5)
90
1
Mr
348.17
Cryst. size, mm3
0.15 ꢃ×ꢃ 0.13 ꢃ×ꢃ 0.12
Monoclinic
P21/c
MeO2C
CO2Me
Crystal system
DMAD
Space group
1
N
N
2
a, Å
b, Å
c, Å
β, deg
V, Å3
Z
9.9064(2)
12.0075(3)
11.9635(3)
100.2240(10)
1400.47(6)
4
Et3N, CHCl3
Scheme 1:ꢀ
1734.53(7)
4
D
calcd, g cm–3
1.651
1.38
μ(MoKα), cm–1
F(000), e
2.271
0.097
a
680
752
hkl range
–14 ꢃꢃ≤ꢃꢃ h ꢃꢃ≤ꢃꢃ +14
–16 ꢃꢃ≤ꢃꢃ k ꢃꢃ≤ꢃꢃ +17
–17 ꢃꢃ≤ꢃꢃ k ꢃꢃ≤ꢃꢃ +17
0.717
–9 ꢃꢃ≤ꢃꢃ h ꢃꢃ≤ꢃꢃ +10
–15 ꢃꢃ≤ꢃꢃ k ꢃꢃ≤ꢃꢃ +15
–29 ꢃꢃ≤ꢃꢃ k ꢃꢃ≤ꢃꢃ +26
0.710
((sinθ)/λ)max, Å–1
Refl. measured/
unique/Rint
16694/4320/0.0243 ꢃ 11217/4711/0.027
Param. refined
ꢃ
163
ꢃ
ꢃ
ꢃ
ꢃ
246
R(F)/wR(F2) (all data)ꢃ 0.0354/0.0563
0.0636/0.1134
1.011
GoF (F2)a
ꢃ
ꢃ
1.036
0.53/–0.47
Δρfin (max/min),
0.24/–0.19
e Å–3
b
Table 2:ꢀSelected bond lengths (Å) and angles (deg) for 1 and 2 with
estimated standard deviations in parentheses.
ꢁ
1ꢁ
2
Distances
ꢂC(17)–N(2)
ꢂC(10)–N(2)
ꢂC(13)–N(2)
ꢂC(9)–C(10)
ꢂC(9)–N(1)
ꢂC(9)–C(8)
ꢂC(13)–C(14)
Angles
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
1.341(2)ꢃ
1.473(3)ꢃ
1.340(3)ꢃ
1.515(3)ꢃ
1.307(2)ꢃ
1.415(3)ꢃ
1.371(3)ꢃ
1.380(2)
1.3967(19)
1.392(2)
1.470(2)
1.3213(19)
1.424(2)
1.423(2)
ꢂC(13)–N(2)–C(17) ꢃ
ꢂC(13)–N(2)–C(10) ꢃ
ꢂN(2)–C(10)–C(9)
ꢂC(17)–N(2)–C(10) ꢃ
ꢂC(10)–C(11)–C(12)ꢃ
ꢂC(11)–C(12)–C(13)ꢃ
ꢂC(12)–C(13)–N(2) ꢃ
120.42(18)ꢃ
121.54(14)
109.38(13)
124.01(13)
128.99(14)
109.47(14)
106.43(15)
107.80(13)
119.91(18)ꢃ
ꢃ
111.39(16)ꢃ
119.44(18)ꢃ
Fig. 1:ꢀOrtep plots of the molecular structures of 1 (a) and 2 (b) in
the crystal and atomnumbering scheme adopted (displacement
ellipsoids at the 50% probability level; H atoms with arbitrary radii;
blue: nitrogen, red: oxygen, green: iodide).
ꢃ
ꢃ
ꢃ
dipolarophile was investigated. Thus, the corresponding 4 Experimental section
substituted indolizine derivative was obtained. Further
investigation of this reaction using other reagents is All chemical reagents and solvents were of analytical
carried out in our laboratory.
grade and were used as received. 1-(Quinolin-2-ylmethyl)
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ꢁꢀꢀꢀ
R. Belguedj et al.: Synthesis of a new quinoline/indolizine hybridꢂ
ꢂ887
pyridinium iodide (1) was synthesized following a litera-
ture procedure [9] starting from quinaldine.
4.3 X-ray structure determinations
Both compounds 1 and 2 were recrystallized from ethyl
acetate giving colorless crystals of the correspond-
ing compound. X-ray data were collected with a Bruker
Apex II CCD area detector diffractometer with a graphite-
monochromatized MoKα radiation (λ ꢁ=ꢁ 0.71073 Å) at T ꢁ=ꢁ
298 K. Refinement of the Flack x parameter for 2 was incon-
clusive due to the absence of sufficient anomalous scatter-
ing. Table 1 summarizes important crystal structure data,
and Table 2 selected bond lengths and angles for 1 and 2.
CCDC 1041774 and 1041775 contain the supplemen-
tary crystallographic data for compounds 1 and 2. These
data can be obtained free of charge from the Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
4.1 1-(Quinolin-2-ylmethyl)pyridinium
iodide (1)
Yield: 95%. Yellow solid, m.p. 242 °C. – 1H NMR
([D6]DMSO, 250 MHz): δ ꢁ=ꢁ 9.04 (d, J ꢁ=ꢁ 6.1 Hz, 2H), 8.62
(t, J ꢁ=ꢁ 7.7 Hz, 1H), 8.41 (dd, J ꢁ=ꢁ 8.4, 1.2 Hz, 1H), 8.13 (t, J ꢁ=ꢁ
6.4 Hz, 2H), 7.93 (d, J ꢁ=ꢁ 8.1 Hz, 1H), 7.75–7.54 (m, 4H), 6.14
(s, 2H) ppm. – 13C NMR ([D6]DMSO, 62.9 MHz): δ ꢁ=ꢁ 154.0,
147.5, 147.2, 146.5, 139.2, 131.2, 129.3, 129.3, 129.0, 128.5,
128.3, 121.1, 126.5 ppm.
4.2 Dimethyl 3-(quinolin-2-yl)indolizine-
1,2-dicarboxylate (2)
Acknowledgments: We are grateful to the Ministère de
l’Enseignement Supérieur et de la Recherche Scientifique
– Algérie (MESRS) for financial support.
A suspension of compound 1 (1.0 mmol) and DMAD (1.1
mmol) in chloroform was stirred at 0 °C, and 1.3 mmol of
triethylamine was added. The mixture was stirred at room References
temperature for 24 h. The solution was evaporated to
[1] For reviews, see: K. T. Potts, in Comprehensive Heterocyclic
dryness under reduced pressure, and the brown residue
was chromatographed on silica gel column using chlo-
roform as eluant. Yield: 32%. Yellow solid, m.p. 171 °C.
Chemistry: The Structure, Reactions, Synthesis, and Uses
of Heterocyclic Compounds, Part 4A (Eds.: A. R. Katritzky,
C. W. Rees), Pergamon Press, Oxford, 1984.
1
– H NMR (CDCl3, 250 MHz): δ ꢁ=ꢁ 9.69 (dd, J ꢁ=ꢁ 7.2, 0.8 Hz,
[2] G. S. Singh, E. E. Mmatli, Eur. J. Med. Chem. 2011, 46, 5237.
[3] Z. Mao, X. Li, X. Lin, P. Lu, Y. Wang, Tetrahedron 2012, 68, 85.
[4] E. Georgescu, M. R. Caira, F. Georgescu, B. Draghici, M. M. Popa,
F. Dumitrascu, Synlett 2009, 2009, 1795.
[5] S. Zama, A. Bouraiou, S. Bouacida, T. Roisnel, A. Belfaitah,
Tetrahedron Lett. 2013, 54, 5605.
[6] H. Boulebd, S. Zama, A. Bouraiou, S. Bouacida, H. Merazig,
A. Belfaitah, Tetrahedron Lett. 2014, 55, 4701.
1H), 8.32 (dd, J ꢁ=ꢁ 9.0, 0.7 Hz, 1H), 8.23 (d, J ꢁ=ꢁ 8.6 Hz, 1H),
8.13 (d, J ꢁ=ꢁ 8.4 Hz, 1H), 7.86 (t, J ꢁ=ꢁ 8.0 Hz, 1H), 7.74 (t, J ꢁ=ꢁ
8.6 Hz, 2H), 7.58 (t, J ꢁ=ꢁ 7.0 Hz, 1H), 7.29 (t, Jꢁ=ꢁ 8.12 Hz, 1H),
6.94 (t, J ꢁ=ꢁ 6.9 Hz, 1H), 3.95 (s, 3H), 3.64 (s, 3H) ppm. – 13
C
NMR (CDCl3, 62.9 MHz): δ ꢁ=ꢁ 167.8, 164.1, 149.7, 147.6, 137.1,
136.6, 130.1, 129.1, 127.7, 126.8, 126.8, 125.3, 125.0, 122.3,
121.3, 119.9, 119.8, 114.2, 102.7, 53.1, 51.6 ppm. – TOF-HRMS [7] M. Schulz, T. Kloubert, H. Görls, M. Westerhausen, Acta Crystal-
logr. 2009, E65, o957.
((+)-CI): m/z ꢁ=ꢁ 361.1199 (calcd. 361.1188 for C21H17N2O4,
[8] W.-J. Gu, J. Zhuang, Y.-L. Jiang, B.-X. Wang, Acta Crystalllogr.
+
[M+H] ).
2011, E67, o123.
[9] J. D. Albright, R. G. Shepherd, J. Heterocycl. Chem. 1973, 10, 899.
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