1-(2′-Benzimidazolylmethyl)-pyridinium ylide in the one-pot synthesis of indolizine and benzimidazo [1,2-a]pyridine derivatives

Article abstract of DOI:10.1515/znb-2015-0016

Four indolizine derivatives were obtained via 1,3-dipolar cycloaddition reaction of 1-(2′-benzimidazolyl-methyl)pyridinium ylide with various electron-deficient alkynes. The reaction of this pyridinium N-ylide with dimethyl maleate gave an unexpected methyl 1-oxo-benzimidazo [1,2-a]pyridine-3-carboxylate. The structures of all reported compounds have been examined by X-ray crystallography and NMR spectroscopy.

Full text of DOI:10.1515/znb-2015-0016

Z. Naturforsch. 2015; aop
Roumaissa Belguedj, Sofiane Bouacida, Hocine Merazig, Ali Belfaitah and
Abdelmalek Bouraiou*
1
-(2′-Benzimidazolylmethyl)-pyridinium ylide
in the one-pot synthesis of indolizine and
benzimidazo[1,2-a]pyridine derivatives
DOI 10.1515/znb-2015-0016
substances [1–3]. Their heteroanalogues, with a heterocy-
clic ring such as pyridine or pyrazine instead of a phenacyl
group, have been used successfully to extend the classical
synthesis of indolizine derivatives [4, 5]. The use of these
Received January 24, 2015; accepted April 2, 2015
Abstract: Four indolizine derivatives were obtained via salts offers the advantage of removing a few reaction steps
1
,3-dipolar cycloaddition reaction of 1-(2′-benzimidazolyl- to reach the target molecule and a simple workup. Fur-
methyl)pyridinium ylide with various electron-deficient thermore, it has recently been reconsidered as a one-pot
alkynes. The reaction of this pyridinium N-ylide with multicomponent process [6, 7].
dimethyl maleate gave an unexpected methyl 1-oxo-
Previously, we have reported that bicyclic mesoionic
benzimidazo[1,2-a]pyridine-3-carboxylate. The structures thiazolo[3,2-a]imidazole derivatives can be formed by
of all reported compounds have been examined by X-ray a reaction involving carbon disulfide and imidazolium
crystallography and NMR spectroscopy.
N-ylide generated in situ from N-phenacyl-2-bromoimida-
zolium salts, in the presence of Et N [8].
3
Keywords: 1,3-dipolar cycloaddition; crystal structure;
indolizine; pyridinium N-ylide.
In continuation of our research interest in heter-
oaromatic N-ylides involving multicomponent reactions,
we report here our results concerning the reactivity of
(
2′-benzimidazolylmethyl)pyridinium ylide towards both
1
Introduction
dimethyl maleate and some alkynes as dipolarophiles.
Pyridone and indolizine derivatives containing a benzi-
N-Phenacylpyridinium salts have found applications as midazole unit were achieved as a result of these reactions.
reagents in the organic synthesis of diverse classes of
*
Corresponding author: Abdelmalek Bouraiou, Unité de Recherche de
2
Results and discussion
Chimie de l’Environnement et Moléculaire Structurale, Université des
frères Mentouri, Constantine 25000, Algérie, Fax: +213-31-81-88-16,
E-mail: bouraiou.abdelmalek@yahoo.fr; Previous address: Equipe
de Synthèse de Molécules à Objectif Thérapeutique, Laboratoire
des Produits Naturels d’Origine Végétale et de Synthèse Organique,
Université des frères Mentouri, Constantine 25000, Algérie
In a preliminary exploratory study, a mixture of
-[(1H-benzo[d]imidazol-2-yl)methyl] pyridinium chloride
(Scheme 1), which was prepared from the reaction of
1
1
pyridine with 2-(chloromethyl)-1H-benzo[d]imidazole as
described previously [9–11], and dimethyl acetylenedi-
carboxylate (DMAD) was stirred at ambient temperature
using chloroform as solvent and in the presence of trieth-
ylamine for 24 h (Scheme 2).
Roumaissa Belguedj: Unité de Recherche de Chimie de
l’Environnement et Moléculaire Structurale, Université des frères
Mentouri, Constantine 25000, Algérie; Previous address: Equipe de
Synthèse de Molécules à Objectif Thérapeutique, Laboratoire des
Produits Naturels d’Origine Végétale et de Synthèse Organique,
Université des frères Mentouri, Constantine 25000, Algérie
After general workup, the obtained compound was
Sofiane Bouacida: Département Sciences de la Matière, Université
Oum El Bouaghi, 04000 Oum El Bouaghi, Algérie; and Unité de
Recherche de Chimie de l’Environnement et Moléculaire Structurale,
Université des frères Mentouri, Constantine 25000, Algérie
Hocine Merazig: Unité de Recherche de Chimie de l’Environnement et
Moléculaire Structurale, Université des frères Mentouri, Constantine
1
13
fully characterized by H, C NMR, and mass spectra. The
formation of indolizine 2a was further confirmed by crystal
structure determination (Fig. 1). Compound 2a comes from
the dehydrogenation of the initially formed cycloadduct
in air. The intermediates, dihydroindolizines and tetrahy-
droindolizine, were not stable enough to be isolated.
This result clearly showed that, due to the elec-
tron withdrawing ability of the pyridinium moiety, the
2
5000, Algérie
Ali Belfaitah: Equipe de Synthèse de Molécules à Objectif Thérapeutique,
Laboratoire des Produits Naturels d’Origine Végétale et de Synthèse
Organique, Université des frères Mentouri, Constantine 25000, Algérie
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 7/1/15 3:25 PM

ꢁꢁꢁꢂ
2ꢀ
ꢀR. Belguedj et al.: 1-(2′-Benzimidazolylmethyl)-pyridinium ylide
from the deposited crystallographic CIF files (see below).
Cl
H
N
Cl
THF
Compound 2a crystallizes in the monoclinic crystal system
H
N
+
N
reflux
(space group P2 /a with Z ꢀ=ꢀ 4). The indolizine ring is close
N
N
1
N
to planarity with a maximum deviation of 0.023(1) Å at
atom C(3). The benzimidazole ring is almost planar, with
a maximum deviation of 0.031(1) Å at C(19) and forms a
dihedral angle with the indolizine ring of 29.88(2)°. The
carbonyl group (C(7)/O(3)–O(4)), attached to C(6), forms
a dihedral angle of 25.83(7)° with the plane defined by the
atoms N(1), C(5)–C(6), C(11)–C(12), while the second car-
bonyl group (C(10)/O(1)–O(2)) attached to the C(11) atom
is rotated by 47.94(5)° out of the same plane. Bond lengths
and angles are in the expected range [12, 13]. The C–N
R2 bonds (N(1)–C(1) 1.382(1), N(1)–C(5) 1.393(1), N(1)–C(12)
1.392(1) Å) in compound 2a indicate partial double bond
character (Table 3, Fig. 2). The packing of the molecule 2a
in the crystal can be described as alternating layers paral-
R2
1
Scheme 1:ꢁPreparation of 1-[(1H-benzo[d]imidazol-2-yl)methyl]
pyridinium chloride 1.
H
N
N
N
R1
N
R2
R1
Et3N
H
N
1
N
N
H
N
CHCl3
−
H
N
R1
lel to the (301) plane. It is stabilized by N–HLO hydrogen
̅
2
a
CO2Me
CO2Me
CO2Et
CO2Me
CO2Et
bonding interactions (Table 4, Fig. 2). The carbomethoxy
methyl group forms a C–HLπ contact to both imidazole
and benzene rings of an adjacent benzimidazole unit. In
addition, the interaction C(18)–H(18)Lπ with an approxi-
mately 3.513(1) Å distance has also been observed (Table 5).
The packing is consolidated by slipped π–π stacking with
a centroid-to-centroid distance of 3.593(1) between pyrrole
and pyridine rings of indolizine with symmetry operation
2
2
b
c
CO2Et
N
N
N
H
H
H
2d
Scheme 2:ꢁFormation of indolizines derivatives 2a-d.
methylene is acidic, and a 1,3-dipolar cycloaddition of the ½ + x, ½ – y, z.
in situ generated ylide with DMAD took place. The favora-
Next, we tried the utility of pyridinium N-ylide for the
ble effect of the benzimidazole substituent on the inter- construction of other heterocyclic moieties. We decided
mediate carbanion stability was confirmed by comparison to test this 1,3-dipolar addition reaction in the presence
with a phenyl substituent. The presence of the benzimida- of an alkene as dipolarophile. In this regard, N-pyridin-
zole group is essential, since no adducts were reported in ium salt 1 was treated with dimethyl maleate in the pres-
the literature using N-benzylpyridinium chloride.
ence of triethylamine as base using chloroform as solvent
To further extend the utility of this reaction, the (Scheme 3).
reactivity of other activated dipolarophiles was explored
Surprisingly, and in contrast to the foregoing reaction
using the same procedure. Four functionalized indolizines results, when the pyridinium N-ylide was treated with
were successfully prepared in 30–45 % yields, and their dimethyl maleate, a polycyclic product 3 was generated in
structures were confirmed by X-ray crystallography and about 25 % of yield. Compound 3 was the main product
NMR spectroscopy (Scheme 2, Fig. 1, Tables 1 and 2).
which could be easily isolated and identified. The struc-
It should be mentioned that the cyclization reactions ture of 3 was unambiguously confirmed by a crystal struc-
of 1 proceed to yield 2c and 2d instead of the others pos- ture determination (Fig. 3, Table 2).
sible regioisomers. The position of the ester group at the
Although the exact mechanism of this reaction
indolizine unit in compounds 2c and 2d was confirmed is not very clear, a plausible reaction course of pyri-
by the structure determinations in the solid state by X-ray dinium ylide with dimethyl maleate is proposed in
diffraction (Fig. 1). It could be noted that the formation of Scheme 4. The 1-(1-(1H-benzo [d]imidazol-2-yl)-4-methoxy-
an indolizine was not observed when pyridinium N-ylide 2-(methoxycarbonyl)-4-oxobutyl)pyridinium chloride A
was stirred with other alkynes, such as phenylacetylene, was formed by a Michael addition reaction of pyridinium
propyne, pentyne, or hexyne.
ylide to the dimethyl maleate. This intermediate under-
In the following, the crystal and molecular structure goes an elimination reaction to generate the dimethyl
of 2a shall be described in more detail (Tables 3–5). Infor- 2-((1H-benzo[d]imidazol-2-yl)methylene)succinate B. This
mation on the other solid-state structures may be taken latter could be deprotonated by Et N giving, via a
3
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 7/1/15 3:25 PM

R. Belguedj et al.: 1-(2′-Benzimidazolylmethyl)-pyridinium ylideꢀꢂꢁꢁꢁꢀ3
1
2c
2d
2
a
2
b
Fig. 1:ꢁOak ridge thermal ellipsoid plots (ORTEP) of the molecular structures of 1, 2a, 2b, 2c, 2d in the crystal and atom numbering scheme
adopted (displacement ellipsoids at the 50 % probability level; H atoms with arbitrary radii; blue: nitrogen, red: oxygen, yellow: chloride).
six-membered ring N-cyclization process, the correspond- methyl 1-oxo-benzimidazo[1,2-a]pyridine-3-carboxylate.
ing 1-oxo-benzimidazo[1,2-a]pyridine derivative 3.
Further investigations of these reactions using others rea-
gents were carried out in our laboratory.
3
Conclusion
4
Experimental section
In conclusion, the 1,3-dipolar cycloaddition reactions of
1
-(2′-benzimidazolylmethyl)pyridinium ylide with various Melting points were determined on an Electrothermal
electron-deficient alkynes and an alkene as dipolaro- Digital Melting Point Apparatus (IA9200, Electrothermal,
1
philes were investigated. Thus, the corresponding substi- Stone, Staffordshire, UK) and are uncorrected. H NMR
13
tuted indolizine derivatives were obtained in the presence and C NMR spectra were recorded on a BRUKER 250 DXP
of activated alkynes. Unexpectedly, the reaction of pyri- (Bruker Instruments, Germany) and VARIAN Mercury 300
dinium N-ylide with dimethyl maleate gave an unexpected spectrometers (Varian Medical Systems, Palo Alto, CA,
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 7/1/15 3:25 PM

ꢁꢁꢁꢂ
4ꢀ ꢀR. Belguedj et al.: 1-(2′-Benzimidazolylmethyl)-pyridinium ylide
Table 1:ꢁCrystal structure data for 1, 2a, 2b.
ꢀ
ꢁ
ꢀ
ꢂa
ꢀ
ꢂb
Formula
r
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
C
H
ꢄꢆClNꢅ
ꢃ
ꢃ
C
H
N O
ꢃ
ꢃ
C
H N Oꢈ
ꢄꢅ
ꢄ9 ꢄꢇ
ꢅꢈ9.ꢅꢈ
ꢅ
ꢈ
ꢆꢄ ꢄ9 ꢅ
ꢅ77.ꢅ9
M
ꢆꢈꢇ.7ꢄ
ꢅ
Crystal size, mm
Crystal system
Space group
a, Å
ꢉ.ꢄꢇ ꢃ×ꢃ ꢉ.ꢉ9 ꢃ×ꢃ ꢉ.ꢉꢄꢆꢃ
ꢉ.ꢆ ꢃ×ꢃ ꢉ.ꢄꢅ ꢃ×ꢃ ꢉ.ꢉ9 ꢃ
ꢉ.ꢆ ꢃ×ꢃ ꢉ.ꢄꢇ ꢃ×ꢃ ꢉ.ꢄꢄ
Monoclinic
Pꢆ /c
Monoclinic
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
Monoclinic
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
Pꢆ /c
Pꢆ /a
ꢄ
ꢄ
ꢄ
9.ꢊꢅꢇꢋ(ꢊ)
9.ꢊꢈꢇꢆ(ꢇ)
ꢄꢅ.ꢄꢈꢇꢅ(7)
9ꢄ.ꢋꢄꢅ(ꢆ)
ꢄꢆꢆꢄ.ꢄꢉ(ꢄꢆ)
ꢈ
7.ꢅꢇꢆꢋ(ꢄ7)
ꢄ7.ꢈꢋꢊ(ꢈ)
ꢄꢆ.ꢈꢉꢊ(ꢅ)
9ꢈ.ꢅꢅꢆ(ꢄꢄ)
ꢄꢇ9ꢉ.ꢇ(ꢊ)
ꢈ
7.ꢈꢆꢊꢋ(ꢆ)
ꢆꢆ.ꢆ7ꢇꢅ(ꢊ)
ꢄꢄ.ꢆ9ꢇꢊ(ꢅ)
9ꢈ.9ꢈ7ꢉ(ꢄꢉ)
ꢄꢋꢊꢄ.7ꢆ(9)
ꢈ
b, Å
c, Å
β, deg
ꢅ
V, Å
Z
D
, g cm–ꢅ
ꢄ.ꢅꢅ7
ꢄ.ꢈꢇ9
ꢄ.ꢅꢈꢊ
calcd
–
ꢄ
μ(MoK ), cm
ꢉ.ꢆ9ꢅ
ꢉ.ꢄꢉꢇ
ꢉ.ꢉ9ꢇ
α
F(ꢉꢉꢉ), e
hkl range
ꢇꢄꢆ
7ꢆꢋ
79ꢆ
–ꢄꢄ ꢃꢃ≤ꢃꢃ h ꢃꢃ≤ꢃꢃ +ꢄꢄ
–9 ꢃꢃ≤ꢃꢃ k ꢃꢃ≤ꢃꢃ +ꢄꢄ
–ꢄꢊ ꢃꢃ≤ꢃꢃ l ꢃꢃ≤ꢃꢃ +ꢄꢇ
ꢉ.ꢊꢄꢋ
–ꢄꢄ ꢃꢃ≤ꢃꢃ h ꢃꢃ≤ꢃꢃ +ꢄꢄ
–ꢆꢊ ꢃꢃ≤ꢃꢃ k ꢃꢃ≤ꢃꢃ +ꢆꢊ
–ꢄꢋ ꢃꢃ≤ꢃꢃ l ꢃꢃ≤ꢃꢃ +ꢄꢈ
ꢉ.7ꢇꢈ
–9 ꢃꢃ≤ꢃꢃ h ꢃꢃ≤ꢃꢃ +9
–ꢆ9 ꢃꢃ≤ꢃꢃ k ꢃꢃ≤ꢃꢃ +ꢆ9
–ꢄꢄ ꢃꢃ≤ꢃꢃ l ꢃꢃ≤ꢃꢃ +ꢄꢈ
ꢉ.ꢊꢇ7
(
(sinθ)/λ) , Å–ꢄ
max
Refl. measured
9ꢆꢉ7
ꢆꢈꢄꢅ/ꢉ.ꢉꢇꢄ9
ꢄꢇꢈ
ꢅ9ꢈꢄꢆ
ꢇꢊꢊ7/ꢉ.ꢉꢆ9ꢆ
ꢆꢅ7
ꢄ79ꢋꢋ
ꢈꢈꢆꢇ/ꢉ.ꢉꢈ9ꢉ
ꢆꢇꢇ
Refl. unique/R
int
Param. refined
ꢆ
R(F)/wR(F ) (I ꢃ>ꢃ ꢆσ(I)) ꢃ
ꢉ.ꢉꢈꢅꢉ/ꢉ.ꢉꢋꢇꢅ
ꢉ.ꢉꢋ7ꢋ/ꢉ.ꢄꢉꢄꢊ
ꢄ.ꢉꢉꢉ
ꢉ.ꢉꢈꢄꢋ/ꢉ.ꢄꢉ99
ꢉ.ꢉꢇ7ꢊ/ꢉ.ꢄꢆꢉꢈ
ꢄ.ꢉꢆ9
ꢉ.ꢉꢈꢋꢆ/ꢉ.ꢄꢉꢇꢆ
ꢉ.ꢉ9ꢊꢊ/ꢉ.ꢄꢆꢇꢉ
ꢄ.ꢉꢄꢆ
ꢆ
R(F)/wR(F ) (all data) ꢃ
ꢆ
Goodness-of-fit on F ꢃ
Δρ (max/min), e Å–
ꢅ
ꢃ
ꢉ.ꢄ99/–ꢉ.ꢆꢅꢇ
ꢉ.ꢈꢇꢊ/–ꢉ.ꢆ7ꢅ
ꢉ.ꢆꢉꢋ/–ꢉ.ꢄ99
fin
Table 2:ꢁCrystal structure data for 2c, 2d, 3.
ꢀ
ꢂc
ꢀ
ꢂd
ꢀ
ꢃ
Formula
r
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
C
H
N O
ꢃ
ꢃ
C
H
N O
ꢃ
ꢃ
C H N Oꢅ
ꢄꢅ ꢄꢉ ꢆ
ꢄ7 ꢄꢅ
ꢆ9ꢄ.ꢅ
ꢅ
ꢆ
ꢄꢋ ꢄꢇ
ꢅꢉꢇ.ꢅꢅ
ꢅ
ꢆ
M
ꢆꢈꢆ.ꢆꢅ
ꢅ
Crystal size, mm
Crystal system
Space group
a, Å
ꢉ.ꢄ9 ꢃ×ꢃ ꢉ.ꢄꢈ ꢃ×ꢃ ꢉ.ꢄꢃ
ꢉ.ꢆꢆ ꢃ×ꢃ ꢉ.ꢄ7 ꢃ×ꢃ ꢉ.ꢉ9ꢃ
Triclinic
Pꢄ
ꢉ.ꢄꢈ ꢃ×ꢃ ꢉ.ꢄ ꢃ×ꢃ ꢉ.ꢉꢋ
Orthorhombic
Monoclinic
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
Pꢆ /n
̅
Pcaꢆ
ꢄ
ꢄ
ꢊ.7ꢊꢊꢉ(ꢄ7)
ꢄꢊ.ꢉ97(ꢈ)
ꢄꢆ.ꢋꢉꢇ(ꢅ)
9ꢉ
ꢊ.9ꢋ7ꢊ(ꢈ)
9.ꢊꢇꢈꢆ(ꢊ)
ꢄꢆ.ꢉꢄꢈꢉ(7)
99.9ꢈꢋ(ꢇ)
ꢄꢉꢉ.ꢉ9ꢊ(ꢅ)
ꢄꢉꢇ.ꢅꢋꢉ(ꢈ)
7ꢈꢋ.ꢇꢅ(ꢋ)
ꢆ
ꢆꢇ.ꢉꢅꢈ(7)
ꢇ.7ꢉꢅꢅ(ꢄꢇ)
7.7ꢅꢋꢈ(ꢄꢊ)
9ꢉ
b, Å
c, Å
α, deg
β, deg
99.7ꢇꢆ(ꢄꢄ)
9ꢉ
9ꢉ
9ꢉ
γ, deg
ꢅ
V, Å
ꢄꢅ7ꢈ.ꢈ(ꢊ)
ꢈ
ꢄꢄꢉꢈ.9(ꢇ)
ꢈ
Z
D
, g cm–ꢅ
ꢄ.ꢈꢉꢋ
ꢄ.ꢅꢇꢇ
ꢄ.ꢈꢇꢊ
calcd
–
ꢄ
μ(MoK ), cm
ꢉ.ꢉ9ꢇ
ꢉ.ꢉ9ꢄ
ꢉ.ꢄꢉꢊ
α
F(ꢉꢉꢉ), e
hkl range
ꢊꢉꢋ
ꢅꢆꢉ
ꢇꢉꢈ
–9 ꢃꢃ≤ꢃꢃ h ꢃꢃ≤ꢃꢃ +ꢋ
–ꢆꢄ ꢃꢃ≤ꢃꢃ k ꢃꢃ≤ꢃꢃ +ꢄ7
–ꢄ7 ꢃꢃ≤ꢃꢃ l ꢃꢃ≤ꢃꢃ +ꢄ7
ꢉ.ꢊꢋꢋ
–ꢋ ꢃꢃ≤ꢃꢃ h ꢃꢃ≤ꢃꢃ +ꢋ
–ꢄꢄ ꢃꢃ≤ꢃꢃ k ꢃꢃ≤ꢃꢃ +ꢄꢄ
–ꢄꢈ ꢃꢃ≤ꢃꢃ l ꢃꢃ≤ꢃꢃ +ꢄꢇ
ꢉ.ꢊꢅꢉ
–ꢅꢆ ꢃꢃ≤ꢃꢃ h ꢃꢃ≤ꢃꢃ +ꢅꢆ
–7 ꢃꢃ≤ꢃꢃ k ꢃꢃ≤ꢃꢃ +ꢈ
–7 ꢃꢃ≤ꢃꢃ l ꢃꢃ≤ꢃꢃ +ꢄꢉ
ꢉ.ꢊꢊꢋ
(
(sinθ)/λ) , Å–ꢄ
max
Refl. measured
ꢄꢈꢊꢄꢋ
ꢅ7ꢆꢈ/ꢉ.ꢉꢊꢆꢋ
ꢆꢉꢉ
ꢋ9ꢆꢋ
ꢆ9ꢄꢇ/ꢉ.ꢉꢈꢅꢆ
ꢆꢄꢉ
ꢇ77ꢋ
ꢆꢆꢆꢈ/ꢉ.ꢉꢅꢈ7
ꢄꢊꢈ
Refl. unique/R
int
Param. refined
ꢆ
R(F)/wR(F ) (I ꢃ>ꢃ ꢆσ(I)) ꢃ
ꢉ.ꢉꢈꢉꢇ/ꢉ.ꢉꢋ9ꢊ
ꢉ.ꢉ9ꢅ9/ꢉ.ꢄꢄ9ꢆ
ꢉ.ꢋ79
ꢉ.ꢉꢈ99/ꢉ.ꢄꢄꢅꢈ
ꢉ.ꢄꢄꢋ7/ꢉ.ꢄꢈꢆꢊ
ꢉ.9ꢋꢆ
ꢉ.ꢉꢅ9ꢄ/ꢉ.ꢉꢋꢇꢊ
ꢉ.ꢉꢇꢆꢋ/ꢉ.ꢉ9ꢄ9
ꢄ.ꢉꢅꢅ
ꢆ
R(F)/wR(F ) (all data) ꢃ
ꢆ
Goodness-of-fit on F ꢃ
Δρ (max/min), e Å–
ꢅ
ꢃ
ꢉ.ꢆꢇꢄ/–ꢉ.ꢆꢋꢇ
ꢉ.ꢆꢉꢄ/–ꢉ.ꢄꢇꢅ
ꢉ.ꢆꢅꢇ/–ꢉ.ꢄꢋꢉ
fin
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 7/1/15 3:25 PM

R. Belguedj et al.: 1-(2′-Benzimidazolylmethyl)-pyridinium ylideꢀꢂꢁꢁꢁꢀ5
Table 3:ꢁSelected bond lengths (Å), angles (deg), and dihe-
dral angles (deg) for 2a with estimated standard deviations in
parentheses.
Spain). Thin layer chromatography (TLC) was carried out
on precoated Merck silica gel aluminum sheets 60 F .
2
54
ꢀ
ꢂa 4.1 General reaction procedure for the
synthesis of indolizines 2
Distances
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢀ
ꢀ
ꢀ
N(ꢄ)–C(ꢄ)
N(ꢄ)–C(ꢇ)
N(ꢄ)–C(ꢄꢆ)
ꢄ.ꢅꢋꢄꢋ(ꢄꢆ)
ꢄ.ꢅ9ꢅꢅ(ꢄꢅ) A suspension of ylide (1.0 mmol) and alkyne (1.1 mmol) in
ꢄ.ꢅ9ꢄ7(ꢄꢆ)
chloroform was stirred at 0 °C. Triethylamine (1.3 mmol)
Angles
was added dropwise, and the mixture was stirred at room
ꢀ
ꢀ
ꢀ
ꢀ
C(ꢄꢆ)–N(ꢄ)–C(ꢇ) ꢃ
C(ꢄ)–N(ꢄ)–C(ꢇ)
N(ꢄ)–C(ꢄꢆ)–C(ꢄꢄ)ꢃ
N(ꢄ)–C(ꢇ)–C(ꢊ)
ꢄꢉ9.ꢊꢉ(ꢋ)
temperature for 24 h. The solution was evaporated to
dryness under reduced pressure, and the brown residue
ꢃ
ꢄꢆꢄ.ꢊꢆ(ꢋ)
ꢄꢉꢊ.ꢋꢄ(ꢋ)
ꢃ
ꢄꢉ7.ꢅꢊ(ꢋ) was chromatographed on a silica gel column.
USA). Chemical shifts (δ values) are expressed in ppm. 4.2 Dimethyl 3-(1H-benzo[d]imidazol-2-yl)
High-resolution mass spectra were recorded on an LC-MS
indolizine-1,2-dicarboxylate (2a)
instrument (Agilent 1200 LC-Agilent 6500 Accurate Mass)
1
and were carried out at the Instituto de Química Orgánica Yield: 32 %; yellow solid; m.p. 189 °C. – H NMR ([D ]pyri-
General (Spanish National Research Council, CSIC, Madrid, dine, 250 MHz): δ ꢀ=ꢀ 13.12 (br, 1H), 10.03 (td, 1H, J ꢀ=ꢀ 7.1, 7.1,
5
Table 4:ꢁDistances (Å) and angles (deg) of intra- and intermolecular hydrogen bonds for 2a.
D–HLA
ꢀ
d(D–H)ꢀ
d(HLA)ꢀ
d(D–A)ꢀ
∠(D–HLA)ꢀ
Symm. op.
N(ꢅ)–H(ꢅN)LO(ꢄ)ꢃ
N(ꢅ)–H(ꢅN)LO(ꢄ)ꢃ
ꢉ.ꢋꢊꢃ
ꢉ.ꢋꢊꢃ
ꢆ.ꢆꢈꢃ
ꢆ.ꢄꢇꢃ
ꢆ.9ꢊꢄꢆ(ꢄꢅ)ꢃ
ꢆ.ꢋꢄꢈ9(ꢄꢈ)ꢃ
ꢄꢈꢆꢃ
ꢄꢅꢈꢃ
–x, –y + ꢄ, –z
x, y, z
Table 5:ꢁIntermolecular interactions C–HLCg (C–HLπ; Å, deg) operating in the crystal structure of 2a.
C–HLCg
ꢀ
d(C–H)ꢀ
d(HLCg)ꢀ
d(C–Cg)ꢀ
∠(D–HLCg)ꢀ
Symm. op.
C(9)–H(9B)LCgꢄ (N(ꢆ)/C(ꢄꢅ)/N(ꢅ)/C(ꢄꢈ)/C(ꢄ9))ꢃ
ꢉ.9ꢊꢃ
ꢉ.9ꢊꢃ
ꢉ.9ꢅꢃ
ꢆ.7ꢊꢃ
ꢆ.9ꢊꢃ
ꢆ.7ꢇꢃ
ꢅ.ꢅꢊꢉ9(ꢄꢇ)ꢃ
ꢅ.ꢋꢋ7ꢊ(ꢄꢊ)ꢃ
ꢅ.ꢇꢄꢅꢄ(ꢄꢈ)ꢃ
ꢄꢆꢄꢃ
ꢄꢊꢈꢃ
ꢄꢈꢉꢃ
–x, –y + ꢆ, –z + ꢆ
–x, –y + ꢆ, –z + ꢆ
x – ꢅ/ꢆ, –y – ꢄ/ꢆ, z
C(9)–H(9B)LCgꢆ (C(ꢄꢈ)–C(ꢄꢋ))
C(ꢄꢋ)–H(ꢄꢋ)LCgꢆ (C(ꢄꢈ)–C(ꢄꢋ))
ꢃ
ꢃ
Fig. 2:ꢁView of the crystal structure of 2a in a projection along [010] showing the formation of layers parallel to the (301
gen bonds are shown as red dashed lines (N–HLO) connecting these layers.
̅
) plane of 2a. Hydro-
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 7/1/15 3:25 PM

ꢁꢁꢁꢂ
6ꢀ ꢀR. Belguedj et al.: 1-(2′-Benzimidazolylmethyl)-pyridinium ylide
MeO2C
CO2Me
O
4.3 Diethyl 3-(1H-benzo[d]imidazol-2-yl)
CO2Me
indolizine-1,2-dicarboxylate (2b)
N
N
N
Et3N, CHCl3
N
H
N
1
Cl
Yield: 30 %; yellow solid; m.p. 161 °C. – H NMR ([D ]DMSO,
H
6
2
50 MHz): δ ꢀ=ꢀ 12.32 (br, 1H), 9.42 (d, 1H, J ꢀ=ꢀ 7.1 Hz), 8.23 (d,
3
(25 %)
1
1
H, J ꢀ=ꢀ 10.9 Hz), 7.74–7.70 (m, 2H), 7.42 (td, 1H, J ꢀ=ꢀ 6.8, 0.8
Hz), 7.32–7.28 (m, 2H), 7.14 (td, 1H, J ꢀ=ꢀ 6.9, 1.1 Hz), 4.43–4.22
Scheme 3:ꢁFormation of 1-oxo-benzimidazo[1,2-a]
13
pyridine-3-carboxylate.
(m, 4H), 1.33 (t, 3H, J ꢀ=ꢀ 7.0 Hz), 1.24 (t, 3H, J ꢀ=ꢀ 7.1 Hz). – C
NMR ([D ]DMSO, 62.9 MHz): δ ꢀ=ꢀ 165.0, 162.7, 142.2, 139.6,
6
1
1
(
35.6, 126.9, 125.9, 123.5, 122.6, 119.0, 115.3, 114.9, 114.8,
02.3, 61.6, 60.0, 14.3, 13.8. – HRMS (ESI): m/z ꢀ=ꢀ 378.1454
+
calcd. 378.1454 for C H N O , [M+H] ).
2
1
20
3
4
4
.4 Methyl 3-(1H-benzo[d]imidazol-2-yl)
indolizine-1-carboxylate (2c)
1
Yield: 45 %; white solid; m.p. 268 °C. – H NMR ([D ]DMSO,
6
3
00 MHz): δ ꢀ=ꢀ 10.23 (d, 1H, J ꢀ=ꢀ 7.2 Hz), 8.23 (d, 1H, J ꢀ=ꢀ 8.7
Hz), 8.17 (s, 1H), 7.72–7.69 (m, 1H), 7.52–7.50 (m, 1H), 7.42 (td,
1
3
1
(
H, J ꢀ=ꢀ 9.3, 0.9 Hz), 7.24–7.19 (m, 3H), 3.85 (s, 3H). – C NMR
Fig. 3:ꢁORTEP plot of the molecular structure of 3 in the crystal and
[D ]DMSO, 75 MHz): δ ꢀ=ꢀ 164.5, 145.9, 144.0, 137.5, 134.3,
atom numbering scheme adopted (displacement ellipsoids at the
6
50 % probability level; H atoms with arbitrary radii).
128.5, 125.6, 123.3, 122.3, 119.4, 119.1, 118.4, 116.2, 114.9, 111.4,
1
04.4, 51.7. – HRMS (ESI): m/z ꢀ=ꢀ 293.1105 (calcd. 293.1111
+
for C H N O , [M+H] ).
17
14
3
2
CO2Me
Cl
Cl
4
.5 Ethyl 3-(1H-benzo[d]imidazol-2-yl)
H
N
H
CO Me
N
2
N
N
indolizine-1-carboxylate (2d)
Et3NH
N
CO Me
2
N
MeO2C
1
−
H
/ + H
Yield: 45 %; white solid; m.p. 165 °C. – H NMR ([D ]DMSO,
6
A
1
250 MHz): δ ꢀ=ꢀ 12.96 (br, 1H), 10.25 (d, 1H, J ꢀ=ꢀ 7.0 Hz), 8.24
(d, 1H, J ꢀ=ꢀ 8.9 Hz), 8.16 (s, 1H), 7.74–7.71 (m, 1H), 7.54–7.51
−
−
H
−
(
(
m, 1H), 7.40 (td, 1H, J ꢀ=ꢀ 9.8, 0.9 Hz), 7.25–7.18 (m, 3H), 4.32
Cl
N
1
3
q, 2H, J ꢀ=ꢀ 7.1 Hz), 1.35 (t, 3H, J ꢀ=ꢀ 4.0 Hz). – C NMR ([D ]
6
H
N
H
N
DMSO, 62.5 MHz): δ ꢀ=ꢀ 163.5, 145.3, 143.4, 136.9, 133.7, 127.9,
24.8, 122.7, 121.6, 118.7, 118.5, 117.7, 115.5, 114.2, 110.8, 104.0,
−
H /− MeO
1
N
N
CO Me
2
CO2Me
59.5, 14.2. – HRMS (ESI): m/z ꢀ=ꢀ 306.1237 (calcd. 306.1243
MeO2C
+
for C H N O , [M+H] ).
O
H
18 16
3
2
B
3
Scheme 4:ꢁProposed mechanism for the formation of 3.
4
.6 Methyl 1-oxo-benzimidazo[1,2-a]pyri-
dine-3-carboxylate (3)
1
Yield: 25 %; white solid; m.p. 192 °C. – H NMR ([D ]DMSO,
6
1
.0 Hz), 8.26 (td, 1H, J ꢀ=ꢀ 9.0, 1.1 Hz), 7.86–8.02 (m, 2H), 7.45– 300 MHz): δ ꢀ=ꢀ 12.94 (br, 1H), 8.87 (d, 1H, J ꢀ=ꢀ 13.7 Hz), 7.67–
7
.37 (m, 2H), 7.21–7.15 (m, 1H), 6.88 (td, 1H, J ꢀ=ꢀ 7.0, 1.3 Hz), 7.55 (m, 2H), 7.38 (td, 1H, J ꢀ=ꢀ 8.3, 1.7 Hz), 6.67 (d, 1H, J ꢀ=ꢀ 1.6
13
13
3
.88 (s, 6H). – C NMR ([D ]pyridine, 62.9 MHz): δ ꢀ=ꢀ 167.9, Hz), 6.43 (d, 1H, J ꢀ=ꢀ 1.5 Hz), 3.93 (s, 3H). – C NMR ([D ]
5
6
1
1
64.3, 144.2, 136.9, 136.2, 128.3, 126.0, 124.1, 123.7, 120.2, DMSO, 75 MHz): δ ꢀ=ꢀ 166.1, 159.1, 144.8, 139.4, 132.5, 127.8,
16.2, 114.9, 104.3, 53.3, 51.8. – HRMS (ESI): m/z ꢀ=ꢀ 350.1138 127.1, 121.7, 116.9, 111.0, 101.9, 83.7, 53.0, 114. – HRMS (ESI):
+
+
(
calcd. 350.1135 for C H N O , [M+H] ).
m/z ꢀ=ꢀ 243.0760 (calcd. 243.0764 for C H N O , [M+H] ).
19
16
3
4
13 11
2
3
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 7/1/15 3:25 PM

R. Belguedj et al.: 1-(2′-Benzimidazolylmethyl)-pyridinium ylideꢀꢂꢁꢁꢁꢀ7
4
.7 X-ray structure determinations
References
X-ray data were collected with a Bruker Apex II CCD area
detector diffractometer with graphite-monochromated
MoK radiation (λ ꢀ=ꢀ 0.71073 Å) at 298 K. Tables 1 and 2
[
1] E. V. Babaev, Rev. J. Chem. 2001, 1, 161, and references cited
therein.
[2] V. Boekelheide, K. Farenholtz, J. Am. Chem. Soc. 1961, 83, 458.
α
[
[
[
3] A. Padwa, D. J. Austin, L. Precedo, L. Zhi, J. Org. Chem. 1993,
summarize important crystal structure data. Figures 1–3
show views of the molecular and crystal structures.
Additional details of the structure determinations may
be taken from the crystallographic CIF files (see the next
paragraph).
CCDC 1041006, 1007307, 1041347, 1007303, 1041920,
and 1007302 contain the supplementary crystallographic
data for compounds 1, 2a, 2b, 2c, 2d, and 3, respec-
tively. These data can be obtained free of charge from the
Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
5
8, 1144.
4] J. Agejas, A. M. Cuadro, M. Pastor, J. J. Vaquero, J.
L. García-Navío, J. Alvarez-Builla, Tetrahedron 1995, 51, 12425.
5] J. Y. Jaung, Y. S. Jung, Bull. Korean Chem. Soc. 2003, 24, 1565.
[6] F. Dumitrascu, E. Georgescu, M. R. Caira, F. Georgescu,
M. M. Popa, B. Draghici, D. G. Dumitrascu, Synlett 2009, 20, 3336.
[
[
[
ꢌ] E. Georgescu, M. R. Caira, F. Georgescu, B. Draghici,
M. M. Popa, F. Dumitrascu, Synlett 2009, 11, 1ꢌꢍ5.
8] S. Zama, A. Bouraiou, S. Bouacida, T. Roisnel, A. Belfaitah,
Tetrahedron Lett. 2013, 54, 5605.
ꢍ] A. J. Charlson, J. S. Harington, Carbohydr. Res. 1975, 43, 383.
[10] E. Alcalde, L. Perez-Garcia, C. Miravitlles, J. Rius, E. Valenti,
J. Org. Chem. 1992, 57, 482ꢍ.
[
[
[
11] A. E. Sparke, C. M. Fisher, R. E. Mewis, S. J. Archibald,
Tetrahedron Lett. 2010, 51, 4ꢌ23.
Acknowledgments: We thank MESRS (Ministère de
l’Enseignement Supérieur et de la Recherche Scientifique)
and ATRST (Agence Thématique de Recherche en Sciences
et Technologie), Algérie, for financial support.
12] M. Schulz, T. Kloubert, H. Görls, M. Westerhausen,
Acta Crystallogr. 2009, E65, oꢍ5ꢌ.
13] W.-J. Gu, J. Zhuang, Y. L. Jiang, B.-X. Wang, Acta Crystallogr.
2011, E67, o123.
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 7/1/15 3:25 PM

Z. Naturforsch.ꢀ
ꢀ2015 | Volume x | Issue x(b)
Graphical synopsis
Roumaissa Belguedj, Sofiane
Bouacida, Hocine Merazig, Ali
Belfaitah and Abdelmalek Bouraiou
1
-(2′-Benzimidazolylmethyl)-pyridinium
ylide in the one-pot synthesis of
indolizine and benzimidazo[1,2-a]
pyridine derivatives
DOI 10.1515/znb-2015-0016
Z. Naturforsch. 2015; x(x)b: xxx–xxx
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 7/1/15 3:25 PM