Fine tuning the outcome of 1,3-dipolar cycloaddition reactions of benzimidazolium ylides to activated alkynes

Article abstract of DOI:10.1016/j.tet.2016.03.086

1,3-Dipolar cycloaddition reactions of benzimidazolium ylides, generated from 3-phenacylbenzimidazolium bromides, to non-symmetrical activated dipolarophiles in various reaction conditions led to complex mixtures of pyrrolo[1,2-a]benzimidazole and pyrrolo[1,2-a]quinoxaline derivatives. In order to explain all experimental results, the influence of reaction conditions on the reaction products was investigated. For the first time, 4-hydroxy-4,5-dihydropyrrolo[1,2-a]quinoxaline derivatives 6, pyrrolo[1,2-a]quinoxalinium quaternary salts 8, as well as 4-methoxy-4,5-dihydropyrrolo[1,2-a]quinoxalines 9, were separated, fully characterized and their interconversions are presented, together with a proposed reaction mechanism.

Full text of DOI:10.1016/j.tet.2016.03.086

Accepted Manuscript
Fine Tuning the Outcome of 1,3-Dipolar Cycloaddition Reactions of Benzimidazolium
Ylides to Activated Alkynes
Emilian Georgescu, Alina Nicolescu, Florentina Georgescu, Florina Teodorescu,
Sergiu Shova, Adriana T. Marinoiu, Florea Dumitrascu, Calin Deleanu
PII:
S0040-4020(16)30228-9
10.1016/j.tet.2016.03.086
TET 27626
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 9 February 2016
Revised Date: 11 March 2016
Accepted Date: 24 March 2016
Please cite this article as: Georgescu E, Nicolescu A, Georgescu F, Teodorescu F, Shova S, Marinoiu
AT, Dumitrascu F, Deleanu C, Fine Tuning the Outcome of 1,3-Dipolar Cycloaddition Reactions of
Benzimidazolium Ylides to Activated Alkynes, Tetrahedron (2016), doi: 10.1016/j.tet.2016.03.086.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Fine Tuning the Outcome of 1,3-Dipolar
Cycloaddition Reactions of Benzimidazolium
Ylides to Activated Alkynes
Leave this area blank for abstract info.
Emilian Georgescu,a Alina Nicolescu,b,c Florentina Georgescu,d Florina Teodorescu,b Sergiu Shova,c,e Adriana T.
Marinoiu,f Florea Dumitrascu,b Calin Deleanu *b,c
a Research Center Oltchim, St. Uzinei 1, RO-240050 Ramnicu Valcea, Romania.
b “C. D. Nenitescu” Centre of Organic Chemistry, Romanian Academy, Spl. Independentei 202B, RO-060023
Bucharest, Romania. E-mail: calin.deleanu@yahoo.com.
c “Petru Poni” Institute of Macromolecular Chemistry, Romanian Academy, Aleea Grigore Ghica Voda 41-A,
RO-700487 Iasi, Romania.
d Research Dept., Teso Spec S. R. L., Str. Muncii 53, RO-915200 Fundulea, Calarasi, Romania.
e Institute of Chemistry, Academy of Sciences, Str. Academiei 3, MD-2028, Chisinau, Republic of Moldova.
f National Research & Development Institute for Cryogenic and Isotopic Technologies, St. Uzinei 4, RO-240050
Ramnicu Valcea, Romania.
O
O
R2
R2
O
O
R3
R3
H2C
N
R
R
R
N
N
R
R
various reaction
conditions
R
R
N
N
N
N
R4
+
O
C
+
+
Br
CH2
Br
R3
N
R3
R
O
R2
R1
R4=OH; H
R1
R1
R1
R2

ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Fine tuning the outcome of 1,3-dipolar cycloaddition reactions of benzimidazolium
ylides to activated alkynes
Emilian Georgescu a, Alina Nicolescu b,c, Florentina Georgescu d, Florina Teodorescu b, Sergiu Shova c,e,
Adriana T. Marinoiu f, Florea Dumitrascu b and Calin Deleanu b,c, 
a Research Center Oltchim, St. Uzinei 1, RO-240050 Ramnicu Valcea, Romania.
b “C. D. Nenitescu” Centre of Organic Chemistry, Romanian Academy, Spl. Independentei 202B, RO-060023 Bucharest, Romania.
c “Petru Poni” Institute of Macromolecular Chemistry, Romanian Academy, Aleea Grigore Ghica Voda 41-A, RO-700487 Iasi, Romania.
d Teso Spec S.R.L., Research Dept., Str. Muncii 53, RO-915200 Fundulea, Calarasi, Romania.
e Institute of Chemistry, Academy of Sciences, Str. Academiei 3, MD-2028, Chisinau, Republic of Moldova.
f National Research & Development Institute for Cryogenic and Isotopic Technologies, St. Uzinei 4, RO-240050 Ramnicu Valcea, Romania.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
1,3-Dipolar cycloaddition reactions of benzimidazolium ylides, generated from 3-
phenacylbenzimidazolium bromides, to non-symmetrical activated dipolarophiles in various
reaction conditions led to complex mixtures of pyrrolo[1,2-a]benzimidazole and pyrrolo[1,2-
a]quinoxaline derivatives. In order to explain all experimental results, the influence of reaction
conditions on the reaction products was investigated. For the first time, 4-hydroxy-4,5-
dihydropyrrolo[1,2-a]quinoxaline derivatives 6, pyrrolo[1,2-a]quinoxalinium quaternary salts 8,
as well as 4-methoxy-4,5-dihydropyrrolo[1,2-a]quinoxalines 9, were separated, fully
characterized and their interconversions are presented, together with a proposed reaction
mechanism.
Available online
Keywords:
Nitrogen heterocycles
Pyrrolo[1,2-a]quinoxaline
Pyrrolo[1,2-a]benzimidazole
Ylides
2009 Elsevier Ltd. All rights reserved.
Cycloaddition
1. Introduction
derivatives demonstrated therapeutic properties on central
nervous system disorders.8
The interest in pyrrolo[1,2-a]benzimidazole and pyrrolo[1,2-
a]quinoxaline derivatives has increased significantly over time,
mainly due to their biological and pharmacological properties.
An interesting synthetic pathway to construct the pyrrolo[1,2-
a]benzimidazole system is based on the classical 1,3-dipolar
cycloaddition reaction of benzimidazolium ylides with electron-
deficient alkynes or alkenes. This process usually starts with the
preparation of benzimidazolium salts, in situ conversion into
corresponding benzimidazolium ylides in the presence of an
inorganic or organic base and 1,3-dipolar cycloaddition reactions
of benzimidazolium ylides with dipolarophiles affording
pyrrolo[1,2-a]benzimidazoles in low to moderate yields.9a-h
Alternatively, the benzimidazolimum salts may also be isolated
for further property studies.9i
Pyrrolo[1,2-a]quinoxalines
substituted
at
C-4
with
alkylpiperazines present both high affinity and selectivity for
anti-serotonin 5-HT3 receptors.1 Pyrrolo[1,2-a]quinoxaline-
carboxylic acid hydrazide derivatives showed antimycobacterial
activity against Mycobacterium tuberculosis,2 while 4-substituted
pyrrolo[1,2-a]quinoxalines exhibited antiparasitic activity upon
Leishmania amazonensis and Leishmania infantum strains.3 2-
(Aminomethyl)-4-phenyl-pyrrolo[1,2-a]quinoxaline derivatives
revealed a central dopamine antagonist activity,4 pyrrolo[1,2-
a]quinoxaline-5-(4H)-yl)sulfonyls and carbonyls were tested as
estrogenic receptor modulators,5 whereas pyrrolo[1,2-
a]quinoxalin-4-yl-hydrazides can be used for treating cancer and
disorders associated with angiogenesis function.6 Antitumor
agents based on the pyrrolo[1,2-a]benzimidazole ring system
were designed as new DNA cross-linkers mimicking the
mitomycin antitumor agents against various human cancer cells,7
and different 2-oxo-pyrrolo[1,2-a]benzimidazole-3-carboxyl
Our group has developed a simple one-pot, multi-component
synthetic strategy towards N-bridgehead heterocyclic compounds.
This strategy is based on the consecutive quaternization of the N-
heterocycle compound, in situ generation of the heterocyclic N-
ylide, 1,3-dipolar cycloaddition reaction to an electron-deficient
alkyne and aromatization sequence, using an epoxide as solvent
and acid scavenger.10 Trying to apply this synthetic protocol to
benzimidazole derivatives we obtained in most cases mixtures of
———
 Corresponding author. Tel.: +40-744-340456; fax: +40-21-3126101; e-mail: calin.deleanu@yahoo.com; calind@icmpp.ro

2
Tetrahedron
ACCEPTED MANUSCRIPT
pyrrolo[1,2-a]benzimidazoles
and
pyrrolo[1,2-
symmetrical activated dipolarophiles in various reaction
a]quinazolines.11a-d Thus, by 1,3-dipolar cycloaddition reactions
of 1-substituted 3-(alkoxycarbonylmethyl)benzimidazolium
ylides to non-symmetrical acetylenic dipolarophiles, we obtained
pyrrolo[1,2-a]quinoxalin-4-ones as major reaction products and
pyrrolo[1,2-a]benzimidazoles as minor reaction products.11b In
the same reaction conditions, by the 1,3-dipolar cycloaddition
reactions of 1-substituted 3-(benzoylmethyl)benzimidazolium
ylides to non-symmetrical acetylenic dipolarophiles, mixtures of
conditions in order to elucidate the formation of pyrrolo[1,2-
a]quinoxalines along with the normal 1,3-dipolar cycloaddition
compounds, pyrrolo[1,2-a]benzimidazoles.
2. Results and discussion
By the reactions of 1-substituted benzimidazoles 1 with
phenacyl bromides 2, 1-substituted 3-phenacylbenzimidazolium
bromides 3 were easily obtained. The 1,3-dipolar cycloaddition
reactions of benzimidazolium ylides, obtained in situ from 1-
substituted 3-phenacylbenzimidazolium bromides 3, in the
presence of various acid acceptors and solvents, with two
different non-symmetrical activated dipolarophiles such as ethyl
propiolate 4 (R3 = OEt) or 3-butyn-2-one 4 (R3 = Me) led to
complex mixtures of pyrrolo[1,2-a]benzimidazoles 5, 4-hydroxy-
4,5-dihydropyrrolo[1,2-a]quinoxalines 6, 4,5-dihydropyrrolo[1,2-
a]quinoxalines 7 and pyrrolo[1,2-a]quinoxaline quaternary salts
8 (Scheme 1). All crude reaction products were analyzed by
HPLC. The identified reaction products were separated by
crystallization based on differences in their solubility.
Pyrrolo[1,2-a]benzimidazole derivatives 5 are very soluble in
chloroform and only slightly soluble in methanol and ethyl
acetate. 4,5-Dihydropyrrolo[1,2-a]quinoxalines 7 are the most
soluble reaction products.
4-phenyl
a]benzimidazoles were obtained.11a,c For the formation of
pyrrolo[1,2-a]quinoxalines along with pyrrolo[1,2-
pyrrolo[1,2-a]quinoxalines
and
pyrrolo[1,2-
a]benzimidazoles via 1,3-dipolar cycloaddition reactions of
benzimidazolium ylides with non-symmetrical activated
acetylenic dipolarophiles, a mechanism involving opening of the
imidazole ring has been proposed.9d,11a-c,12 The mechanism was
also supported by the isolation of open chain intermediates.11c,d
Further research aims to clarify the reaction mechanism for
the formation of 5-substituted pyrrolo[1,2-a]quinoxalines and
pyrrolo[1,2-a]benzimidazoles via 1,3-dipolar cycloaddition reactions
of benzimidazolium ylides, generated in situ from the
benzimidazolium
dipolarophiles.
bromides,
with
activated
acetylenic
Herein, we present an extensive study on the 1,3-dipolar
cycloaddition reaction of benzimidazolium ylides, generated in
situ from the 3-phenacylbenzimidazolium bromide, with non-
.
R2
O
H2C
R2
O C
R
R
R
R3
N
N
4
Br
+
N
N
R
O C
Br
CH2
CH2
CH2
R1
R1
3
2
1
O
O
R2
O
R3
R3
R
R
R
N
R
R
N
N
R4
+
+
X
R3
N
R
N
N
O
CH2
CH2
R2
CH2
R2
R1
R1
R1
6: R4=OH
7: R4=H
5
8
Scheme 1. The reaction scheme for one-pot synthesis of pyrrolo[1,2-a]benzimidazoles and pyrrolo[1,2-a]quinoxalines.
In order to explain these experimental results, we investigated
the influence of reaction conditions on the reaction product yields
in the above described cycloadditions. Therefore, the 1,3-dipolar
cycloaddition reactions of the various benzimidazolium ylides
products have been identified by HPLC analysis of crude
reaction mixtures in the same conditions, as described in the
experimental section.
The 1,3-dipolar cycloaddition reactions of the corresponding
benzimidazolium ylide generated in situ from the 1-benzyl-3-(4’-
fluorophenacyl)-benzimidazolium bromide with ethyl propiolate
were performed in different reaction conditions and the obtained
results are presented in Table 1.
generated
in
situ
from
the
corresponding
3-
phenacylbenzimidazolium bromide 3 with ethyl propiolate, as
well as with 3-butyn-2-one, were performed in the presence of
various acid acceptors and solvents, with or without
tetrapyridinecobalt(II)dichromate (TPCD)13 as oxidant to
promote aromatization of the primary cycloadduct. Final reaction

ACCEPTED MANUSCRIPT
.
Table 1. The influence of reaction conditions on reaction product yields in the reaction of 1-benzyl-3-(4’-
fluorophenacyl)benzimidazolium bromide with ethyl propiolate.
Reaction products yields (%)*
Entry
Reaction conditions
1,2-epoxybutane, 70 h, rt
5
6
7
8
5
1
2
3
4
5
6
54
46
66
25
77
20
10
12
14
10
-
21
28
5
1,2-epoxybutane, 24 h, reflux
1,2-epoxybutane + TPCD, 24 h, reflux
NEt3 in acetonitrile, 3 h, reflux
NEt3 + TPCD in DMF, 2 h, 90 oC
K2CO3 in DMF, 2 days, rt
7
6
16
6
20
13
25
15
18
* Calculated from HPLC chromatograms.
Similarly, the 1,3-dipolar cycloaddition reactions of the
corresponding benzimidazolium ylide generated in situ from the
1-benzyl-3-(4’-chlorophenacyl)-benzimidazolium bromide with
3-butyn-2-one were carried out in different reaction conditions
and the results are presented in Table 2.
.
Table 2. The influence of reaction conditions on reaction product yields in the reaction of 1-benzyl-3-(4’-
chlorophenacyl)benzimidazolium bromide with 3-butyn-2-one.
Reaction products yields (%) *
Entry
Reaction conditions
1,2-epoxybutane, 150 h, 5 ºC
5
6
7
8
-
1
2
3
4
5
6
7
30
24
21
13
15
78
20
6
60
48
40
23
12
-
1,2-epoxybutane, 70 h, rt
12
19
25
35
-
3
1,2-epoxybutane, 24 h, reflux
1,2-epoxybutane, MW, 40 min., 125 ºC
NEt3 in acetonitrile, 3 h, reflux
NEt3 + TPCD in DMF, 2 h, 90 ºC
K2CO3 in DMF, 2 days, rt
7
33
21
12
26
25
8
* Calculated from HPLC chromatograms.
In 1,3-dipolar cycloaddition reactions of benzimidazolium
ylides with ethyl propiolate, carried out in the presence of
epoxides, the major reaction product is the corresponding
pyrrolo[1,2-a]benzimidazole 5 while, in the same reaction
conditions, when 3-butyn-2-one is used as dipolarophile the
major reaction products are pyrrolo[1,2-a]quinoxaline derivatives
6-8. The results could be explained by a better stabilization of the
intermediate primary cycloadduct bearing a carbethoxy group in
comparison to an acetyl group.
same reactions carried out in the presence of an epoxide and
TPCD at 65 ºC, pyrrolo[1,2-a]benzimidazoles 5 are still the
major reaction products but the amounts of pyrrolo[1,2-
a]quinoxalines increase. Other oxidants, such as CrO3, MnO2 or
chloranil, cannot be used together with epoxides.
These differences could be explained by
a different
mechanism in the generation of benzimidazolium ylides in the
presence of organic or inorganic bases than in the presence of
epoxides. In the presence of an inorganic or organic base, the
benzimidazolium ylide is easily generated by the deprotonation
of the 3-phenacylbenzimidazolium salt. In the presence of
epoxides, the benzimidazolium ylide generation implies the
attack of the bromide ion of 3-phenacylbenzimidazolium salt on
the oxirane ring. The reactive intermediate obtained by the ring
opening of the oxirane extracts a methylene proton from the 3-
phenacyl-benzimidazolium salt generating slowly the
corresponding benzimidazolium ylide. In both cases, the in situ
generated benzimidazolium ylide reacts further with the
acetylenic dipolarophile to give a primary cycloadduct which
spontaneously dehydrogenates and rearranges to the
By increasing the reaction temperature, the amount of
pyrrolo[1,2-a]benzimidazole 5 decreases while the amount of
pyrrolo[1,2-a]quinoxaline
derivatives
6-9
increases,
independently of the employed dipolarophile.
In all 1,3-dipolar cycloaddition reactions of benzimidazolium
ylides, generated in situ from 3-phenacylbenzimidazolium
bromides 3, with both ethyl propiolate or 3-butyn-2-one, in the
presence of triethylamine and an oxidant such as TPCD in DMF
at 90 ºC, normal cycloaddition products, pyrrolo[1,2-
a]benzimidazoles 5 are the major reaction products along with
small amounts of pyrrolo[1,2-a]quinoxalinium salts 8. In the

4
Tetrahedron
ACCEPTED MANUSCRIPT
thermodynamically more stable aromatized pyrrolo[1,2-
The ratio of pyrrolo[1,2-a]quinoxalines 6-8 to pyrrolo[1,2-
a]benzimidazole increase slightly when an electron-
a]benzimidazole 5. Obviously, pyrrolo[1,2-a]benzimidazoles 5
are major reaction products in good yields, when the 1,3-dipolar
cycloaddition reactions of 3-phenacyl-benzimidazolium ylides
with activated alkynes are carried out in the presence of
triethylamine and an oxidant such as TPCD at 90 ºC.
5
withdrawing substituent is present on the phenyl group from 3-
phenacyl-benzimidazolium bromides 3 (Table 3).
.
Table 3. The influence of substituents from 3-phenacyl-benzimidazolium bromides 3 on reaction product yields.
Entry
R2
R3
Reaction conditions
1,2-epoxybutane, 70 h, rt
Yields ratio 6-8 / 5*
2.7
3.3
2.6
3.1
4.3
4.6
3.5
3.6
1
4-F
Me
1,2-epoxybutane, 24 h, reflux
1,2-epoxybutane, 70 h, rt
2
3
4
4-Cl
Me
Me
Me
1,2-epoxybutane, 24 h, reflux
1,2-epoxybutane, 70 h, rt
3-NO2
4-NO2
1,2-epoxybutane, 24 h, reflux
1,2-epoxybutane, 70 h, rt
1,2-epoxybutane, 24 h, reflux
* Calculated from HPLC chromatograms.
During the separation and purification procedures for the
reaction products identified by HPLC, when we tried to
crystallize 4-hydroxy-4,5-dihydropyrrolo[1,2-a]quinoxalines 6 or
4,5-dihydropyrrolo[1,2-a]quinoxalines 7 from CHCl3 containing
traces of acidity we obtained a mixture that also contained
various amounts of pyrrolo[1,2-a]quinoxaline quaternary salts 8.
a]quinoxaline quaternary salts
8
are obtained in almost
quantitative yields through the reaction of dihydropyrrolo[1,2-
a]quinoxalines 6 or 7 with acids. The treatment of pyrrolo[1,2-
a]quinoxaline quaternary salts 8 with sodium hydroxide led back
to reaction products 6, while their treatment with sodium
methoxide gave pyrrolo[1,2-a]quinoxalines 9 (Scheme 2), both in
When
samples
of
4-hydroxy-4,5-dihydropyrrolo[1,2-
over 70
%
yields. Moreover, 4-methoxypyrrolo[1,2-
a]quinoxalines 6 or 4,5-dihydropyrrolo[1,2-a]quinoxalines 7
were dissolved in a mixture of CDCl3 and trifluoroacetic acid the
1H and 13C NMR spectra of pyrrolo[1,2-a]quinoxaline quaternary
a]quinoxaline derivatives 9 were identified and isolated during
the crystallization procedure of several pyrrolo[1,2-
a]quinoxalines 6 from methanol.
salts
8
were obtained. We observed that pyrrolo[1,2-
O
R3
O
R
R
N
NaOH
R3
OH
N
R
R
N
CH2
R2
R1
X
N
6
CH2
O
R2
R1
R3
8
R
R
N
MeONa
OMe
N
CH2
R2
R1
9
Scheme 2. The formation of 4-hydroxy-pyrrolo[1,2-a]quinoxalines 6 and 4-methoxy-pyrrolo[1,2-a]quinoxalines 9 from pyrrolo[1,2-
a]quinoxaline quaternary salts 8.

ACCEPTED MANUSCRIPT
During the work-up of the reaction mixture resulting from the
1,3-dipolar cycloaddition reaction of 1-benzyl-3-
imidazole ring opening initiated by the deprotonation at the C-1
position of the primary cycloadduct (A), followed by the rotation
of the pyrrole ring around the carbon-nitrogen single bond and
the cyclization of the open intermediate (B) involving the
benzoyl C=O group to give the pyrrolo[1,2-a]quinoxaline 6.11a-c
The presence of a carbethoxy group in position 3 of the primary
cycloadduct (A) contributes to the better stabilization of this
intermediate structure leading to increased amounts of
pyrrolo[1,2-a]benzimidazoles in comparison with compounds
bearing an acetyl group in the same position 3. The imidazole
ring opening seems to be assisted by the presence of an electron-
withdrawing group on the phenyl ring in the primary cycloadduct
(A), as well as the cyclization of the open intermediate (B),
resulting in increased amounts of pyrrolo[1,2-a]quinoxalines.
Pyrrolo[1,2-a]quinoxaline derivatives 6 are relatively stable and
isolable compounds in basic media, but very unstable in acid
media when the OH group is easily eliminated as water with
formation of pyrrolo[1,2-a]quinoxaline quaternary salts 8. The
elimination of the OH group from pyrrolo[1,2-a]quinoxaline 6
led to an intermediate carbocation (C). The transfer of a hydride
ion from the primary cycloadduct (A) to the intermediate
carbocation (C) led to the pyrrolo[1,2-a]quinoxaline 7. From the
intermediate carbocation (C), the iminium salts, pyrrolo[1,2-
a]quinoxalines 8, are also formed. The aromatized pyrrolo[1,2-
a]quinoxalines 10 are formed from the pyrrolo[1,2-
a]quinoxalines 6 by the formal loss of an alcohol in a
dealkylative elimination process (Scheme 3).
phenacylbenzimidazolium bromide with ethyl propiolate in 1,2-
epoxybutane at reflux, after major reaction products were
separated, the remaining filtrate was evaporated to dryness, the
residue was dissolved in acetone, the insoluble part was collected
1
by filtration and recrystallized from methanol. Based on H, 13C
and 15N NMR spectra we assigned the structure of ethyl 4-
phenylpyrrolo[1,2-a]quinoxaline-2-carboxylate (10) to this later
compound. This product was identified in the HPLC
chromatogram of crude mixture in concentration of about 6%.
Similar products without a benzyl group at the N-5 position seem
to be present in the majority of the crude reaction mixture HPLC
chromatograms. The intensity of these peaks increase with the
reaction temperature, but they still remain minor peaks, and at
this stage they have not been isolated for further structure
elucidation.
All experimental data confirm that the 1,3-dipolar
cycloaddition reactions of the benzimidazolium ylide generated
in situ from 3-phenacylbenzimidazolium bromides with the non-
symmetrical activated dipolarophile in different reaction
conditions involve the initial formation of 1,3-dipolar
cycloaddition adducts (A) from which pyrrolo[1,2-
a]benzimidazole derivatives 5 are subsequently formed (Scheme
3).11a-d
The reaction mechanism for the formation of 4,5-
dihydropyrrolo[1,2-a]quinoxaline 6 (Scheme 3) involves the
.
O
R3
R2
O
R2
O
H
R
R
N
R
N
R
O
N
R3
R3
NH
R
O
NH
N
H
R
O
CH2
CH2
R1
CH2
R1
R1
R2
(B)
(A)
O
O
O
R3
R3
R3
R
R
N
N
R
R
N
R
R
N
(A)
H
OH
H
-H2O
N
N
R2
R2
R2
CH2
CH2
6
CH2
R1
R1
R1
7
(C)
-R1CH2OH
O

O
R3
R3
Br
R
N
Br
R
R
N
R
N
R2
CH2
N
R1
R2
10
8

6
Tetrahedron
ACCEPTED MANUSCRIPT
Scheme 3. The reaction mechanism for the formation of pyrrolo[1,2-a]quinoxaline derivatives.
The isolation and characterization of 4-hydroxy-pyrrolo[1,2-
Compounds isolated and characterized from these reactions
are presented in Table 4. They have been synthesized in different
reaction conditions in order to characterize all reaction products.
a]quinoxalines 6, intermediates in formation of pyrrolo[1,2-
a]quinoxalines 7, 8 and 10, together with the previously reported
separation and characterization of the open intermediates type
(B)11c,d supports the above proposed reaction mechanism.
.
Table 4. The isolated reaction products.
Comp.
R
R1
R2
R3
Reaction products mp (ºC)
5
6
7
8
9
a
b
c
H
H
H
H
H
H
H
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
4-Cl
4-OMe
3-NO2
4-NO2
H
Me
Me
Me
Me
Me
OEt
OEt
OEt
137-139*
178-180
130-132
209-211
232-234
190-192
182-183
192-194*
155-157*
200-202
196-198
187-189
223-225
280-282
157-159
168-170
d
e
99-101
f
140-142
155-157
g
h
4-F
157-159
170-172
193-195
196-197
4-Cl
148-150*
i
j
H
Ph
Me
Me
Ph
Ph
Ph
Ph
4-NO2
4-NO2
4-Cl
H
OEt
Me
210-212
304-306
173-175
233-235
208-209
188-190
221-223
176-178
196-198
154-156
165-166
236-238
261-263
240-242
226-228
197-198
Me
Me
Me
Me
Me
Me
k
l
OEt
Me
149-151
m
n
o
H
OEt
OEt
OEt
164-166
159-161
4-Me
4-NO2
176-178
208-210
* reported in reference 11a.
Our studies on 1,3-dipolar cycloaddition reactions of
benzimidazolium ylides with activated alkynes showed that by
tuning the reaction conditions it is possible to influence the
reaction course towards either pyrrolo[1,2-a]benzimidazole or
pyrrolo[1,2-a]quinoxaline derivatives. Thus, pyrrolo[1,2-
a]benzimidazoles are obtained in good yields in the presence of
an oxidant, such as tetrapyridinecobalt(II)dichromate, using
different tertiary amines. Pyrrolo[1,2-a]quinoxalin-4-ones are the
major reaction products when starting from 1-alkyl-3-
(alkoxycarbonylmethyl)benzimidazolium bromides and tertiary
amines to generate the corresponding benzimidazolium
presence of a tertiary amine led to pyrrolo[1,2-a]quinoxaline
derivatives 6 or 8 as major reaction products.
The structures of pyrrolo[1,2-a]benzimidazoles
5
and
pyrrolo[1,2-a]quinoxalines 6-10 were assigned by elemental
1
analysis, IR and NMR spectroscopy. The H, 13C and 15N NMR
chemical shifts have been unambiguously assigned based on the
following 2D NMR experiments: H,H-COSY, H,C-HSQC, H,C-
HMBC, H,N-HMBC, H,H-NOESY.
X-ray crystallography data for the pair of compounds 6g and
8g (figure 1), confirm the proposed structures and support the
interconversion reactions (Scheme 2).
ylides.11b,d
4-Phenyl-substituted
pyrrolo[1,2-a]quinoxalines
derivatives 7 are obtained as major reaction products starting
from 1-alkyl-3-phenacylbenzimidazolium bromides in the
presence of epoxides. The same reaction carried out in the
.

ACCEPTED MANUSCRIPT
Figure 1. X-ray molecular structures for compounds 6g (left) and 8g (right). Thermal ellipsoids are drawn at 50% probability level.
3. Conclusion
The NMR spectra have been recorded on a Bruker Avance III
400 instrument operating at 400.1, 376.4, 100.6 and 40.6 MHz
for 1H, 19F, 13C, and 15N nuclei respectively. Samples were
transferred in 5 mm Wilmad 507 NMR tubes and recorded with
either a 5 mm multinuclear inverse detection z-gradient probe (1H
spectra and all H-C/H-N 2D experiments) or with a 5 mm four
nuclei direct detection z-gradient probe (13C and 19F spectra).
Chemical shifts are reported in δ units (ppm) and were referenced
1,3-Dipolar cycloaddition reactions of benzimidazolium
ylides, generated from 3-phenacylbenzimidazolium bromides, to
non-symmetrical activated dipolarophiles in various reaction
conditions led to complex mixtures of pyrrolo[1,2-
a]benzimidazole and pyrrolo[1,2-a]quinoxaline derivatives. In
order to rationalize the results, the influence of experimental
conditions on the reaction course was investigated. For the first
1
to internal TMS for H chemical shifts, to the internal deuterated
solvent for 13C chemical shifts (CDCl3 referenced at 77.0 ppm),
electronically referenced to CFCl3 (0 ppm) for 19F chemical
shifts, and referenced to liquid ammonia (0.0 ppm) using
nitromethane (380.2 ppm) as external standard for 15N chemical
shifts. Unambiguous 1D NMR signal assignments were made
based on 2D NMR homo- and heterocorrelation. H,H-COSY,
H,C-HSQC and H,C-HMBC experiments were recorded using
standard pulse sequences in the version with z-gradients, as
delivered by Bruker with TopSpin 2.1 PL6 spectrometer control
and processing software. The individual chemical shifts,
multiplicities and coupling constants for overlapping signals have
been obtained from undecoupled H,C-HSQC experiments
recorded using the pulse sequence described by S. Simova.14 The
15N chemical shifts were obtained as projections from the 2D
indirectly detected H,N-HMBC spectra, employing a standard
pulse sequence in the version with z-gradients as delivered by
Bruker (TopSpin 2.1 PL6).
time,
4-hydroxy-4,5-dihydropyrrolo[1,2-a]quinoxaline
derivatives 6, formed through the cyclization reactions of open
amino intermediates type B, pyrrolo[1,2-a]quinoxalinium
quaternary salts
a]quinoxalines 9 were separated and fully characterized and their
interconversion reactions were presented. mechanism
explaining the formation of all 1,3-dipolar cycloaddition reaction
products was presented. The possibility of influencing the course
of synthesis towards either pyrrolo[1,2-a]benzimidazole or
pyrrolo[1,2-a]quinoxaline derivatives by tuning the 1,3-dipolar
cycloaddition reaction conditions was described.
8
and 4-methoxy-4,5-dihydropyrrolo[1,2-
A
4. Experimental
General. Melting points were measured on a Boëtius hot plate
microscope and are uncorrected. IR spectra were recorded on a
Nicolet Impact 410 spectrometer, in KBr pellets. The high
performance liquid chromatography (HPLC) analyses were
performed with an Agilent Chromatograph 1200 Series at room
temperature by isocratic elution of acetonitrile on an Agilent
Zorbax SB-C18 (250x4.6) column with flow rate 1.0 mL/min.
Final reaction products have been identified as follow: 2-3 drops
of each crude reaction mixture resulting from the 1,3-dipolar
cycloaddition reactions carried out in the presence of epoxides
was transferred into a vial, the solvent was removed under
vacuum, the remaining solid was dissolved in acetonitrile and
analyzed by HPLC. Each crude reaction mixture resulting from
the 1,3-dipolar cycloaddition reactions carried out in the presence
of bases (1-2 mL) was dissolved in 15 mL of CHCl3 washed with
water, dried on Na2SO4 anh. and concentrated under vacuum.
Then, 2-3 drops of each residue was transferred into a vial, the
solvent was removed under vacuum, the remaining solid was
dissolved in acetonitrile and analyzed by HPLC. All major
reaction components were identified. The order of elution of
reaction mixture components in the HPLC analysis conditions
was: 6 < 7 < 8 < 5.
Elemental analyses for C, H and N were obtained using a
COSTECH Instruments EAS32. Satisfactory microanalyses for
all new compounds were obtained.
Benzimidazole, 5,6-dimethylbenzimidazole, ethyl propiolate,
3-butyn-2-one and phenacyl bromides were purchased from
Aldrich and used without further purification. 1-
Benzylbenzimidazole, 1-benzyl-5,6-dimethylbenzimidazole and
1-ethyl-5,6-dimethyl-benzimidazole derivatives were obtained
from the corresponding benzimidazoles and benzyl chloride, or
ethyl
bromide
respectively.
3-Phenacylbenzimidazolium
bromides (3) were obtained from 1-substituted benzimidazole
and phenacyl bromides (2) in acetone, according previously
reported methods.9b Tetrapyridinecobalt(II)dichromate (TPCD)
was obtained according to the previously reported method.13
Chloroform used was stored on K2CO3 anhydrous.

8
Tetrahedron
ACCEPTED MANUSCRIPT
X-Ray crystallographic measurements were carried out with
an Oxford-Diffraction XCALIBUR CCD diffractometer
was filtered off and recrystallized from CHCl3/MeOH to obtain
E
pyrrolo[1,2-a]benzimidazole 5.
equipped with graphite-monochromated Mo-Kα radiation. Single
crystals were positioned at 40 mm from the detector and 832, and
211 frames were measured each for 6, and 50 s over 1° scan
width for 1736, and 2037, respectively. The unit cell
determination and data integration were carried out using the
CrysAlis package of Oxford Diffraction.15 The structures were
solved by direct methods using Olex216 and refined by full-matrix
least-squares on F² with SHELXL-97.17 Atomic displacements
for non-hydrogen, atoms were refined using an anisotropic
model. All H atoms were introduced in idealized positions (dCH
Reactions of 3-phenacylbenzimidazolium bromides (3)
with non-symmetrical dipolarophiles (4) in the presence of
triethylamine and TPCD in DMF. To a solution of a 3-
phenacylbenzimidazolium bromide 3 (2 mmol) in 20 mL of
DMF, a non-symmetrical substituted dipolarophile 4 (2.5 mmol),
0.8 g (1.3 mmol) TPCD and 0.5 g (5 mmol) triethylamine were
added. The reaction mixture was heated at 90 ºC for 2 h, then
cooled and poured under stirring in the 30 mL of HCl (5 % in
water) and extracted with CHCl3 (3 x 50mL). The combined
extracts were dried on NaSO4 anh. and the solvent was removed
under vacuum. The solid was triturated with MeOH, the solid
was recovered by filtration and recrystallized from CHCl3/MeOH
to obtain the pyrrolo[1,2-a]benzimidazole 5. Samples for HPLC
analysis were separately worked-up as it was described above.
=
0.96 Å) using the riding model with their isotropic
displacement parameters fixed at 120% of their riding atom.
DMF solvate molecules were found to be disordered in two
resolvable positions and their positional parameters were refined
in combination with PART and SADI restraints using isotropic
model for non-H atoms. The molecular plots were obtained using
the Olex2 program.
Reactions of 3-phenacylbenzimidazolium bromides (3)
with non-symmetrical dipolarophiles (4) in the presence of
K2CO3 in DMF. To a solution of a 3-phenacylbenzimidazolium
bromide 3 (2 mmol) and 0.69 g (5 mmol) of K2CO3 in 20 mL of
DMF, a non-symmetrical substituted dipolarophile 4 (2.5 mmol),
was added and the mixture was stirred for two days at room
temperature. The solid was filtered off, the filtrate was
concentrated in vacuo, diluted with 50 mL CHCl3, washed with
water (2 x 50 mL), and dried on Na2SO4 anh. The solvent was
partly removed in vacuo, diluted with MeOH and the solid was
filtered, washed on the filter with Et2O and the obtained
pyrrolo[1,2-a]quinoxaline 6 recrystallized from CHCl3/Et2O.
Reactions of 3-phenacylbenzimidazolium bromides (3)
with non-symmetrical dipolarophiles (4) in 1,2-epoxybutane
at room temperature. To
a
suspension of
a
3-
phenacylbenzimidazolium bromide 3 (2 mmol) in 25 mL of 1,2-
epoxybutane a non-symmetrical substituted dipolarophile 4 (2.5
mmol) was added and stirred at room temperature for 70 h. The
solvent was partly evaporated in vacuo, 3-5 mL of MeOH added
under a gentle stirring and the mixture left for 2 h in the
refrigerator. The solid formed was filtered and recrystallized
from CHCl3/MeOH giving the pyrrolo[1,2-a]benzimidazole 5.
The filtrate was concentrated in vacuo to dryness, triturated with
MeOH or EtOAc and the insoluble part containing pyrrolo[1,2-
a]quinoxalines 6 and 8 was filtered off. The resultant solution
was concentrated in vacuo to dryness, washed with Et2O and
triturated with EtOAc. The insoluble part containing pyrrolo[1,2-
1-(4-Chlorobenzoyl)-3-acetyl-4-benzyl-4H-pyrrolo[1,2-
a]benzimidazole (5b). Pale yellow crystals, mp 178-180 ºC
(CHCl3/MeOH). FT-IR (νmax, cm-1) 1651, 1613, 1548, 1495,
1
1446, 1392, 1296, 1265, 1203, 1157, 1086. H NMR (CDCl3) δ
(ppm): 2.45 (3H, s, CH3), 6.24 (2H, s, CH2), 7.20-7.37 (8H, m,
aromatic rings), 7.40 (1H, s, H-2), 7.52 (2H, d, J 8.4 Hz, H-3’),
7.85 (2H, d, J 8.4 Hz, H-2’), 8.89 (1H, d, J 7.4 Hz, H-8). The
individual chemical shifts, multiplicities and coupling constants
for the 7.20-7.37 ppm multiplet were obtained from undecoupled
HSQC as follows: 7.20 (2H, d, J 6.9 Hz, H-2”), 7.23 (1H, t, J 7.4
Hz, H-4”), 7.26 (2H, t, J 7.7 Hz, H-3”), 7.33 (1H, t, J 7.9 Hz, H-
7), 7.35 (1H, d, J 8.4 Hz, H-5), 7.36 (1H, t, J 8.1 Hz, H-6). 13C
NMR (CDCl3) δ (ppm): 27.6 (CH3), 49.3 (CH2), 104.3 (C-3),
110.8 (C-5), 117.3 (C-8), 120.9 (C-1), 122.1 (C-7), 124.8 (C-6),
126.8 (C-2”), 127.2 (C-8a), 127.7 (C-4”), 128.7 (C-3’), 128.8 (C-
3”), 130.38 (C-2’), 130.41 (C-2), 136.3 (C-4a), 136.8 (C-1”),
137.8 (C-4’ and C-1’), 143.7 (C-3a), 181.9 (CO), 191.2
(COCH3). 15N NMR (CDCl3) δ (ppm): 122.5 (N-4), 174.4 (N-9).
Anal. Calcd. for C26H19ClN2O2 (426.89): C, 73.15; H, 4.49; N,
6.56%. Found: C, 73.40; H, 4.37; N, 6.60%.
a]quinoxaline
7 was filtered off and recrystallized from
MeOH/Et2O.
Reactions of 3-phenacylbenzimidazolium bromides (3)
with non-symmetrical dipolarophiles (4) in 1,2-epoxybutane
at reflux. To a suspension of a 3-phenacylbenzimidazolium
bromide 3 (2 mmol) in 25 mL of 1,2-epoxybutane a non-
symmetrical substituted dipolarophile 4 (2.5 mmol) was added
and the reaction mixture was heated at reflux for 24 h. The
solvent was partly removed under vacuum, 5 mL of MeOH was
added under a gentle stirring and the mixture was left for 2 h in
the refrigerator. The solid formed was filtered off and
recrystallized from CHCl3/MeOH giving the pyrrolo[1,2-
a]benzimidazole 5. The filtrate was worked up as it was
described above.
Reactions of 3-phenacylbenzimidazolium bromides (3)
with non-symmetrical dipolarophiles (4) in the presence of
triethylamine in acetonitrile. To a suspension of a 3-
phenacylbenzimidazolium bromide 3 (2 mmol) in 20 mL of
acetonitrile a non-symmetrical substituted dipolarophile 4 (2.5
mmol) was added under stirring, then a solution of 0.5 g (5
mmol) of triethylamine in 5 mL of acetonitrile was added
dropwise. The reaction mixture was heated at reflux for 3 h. The
solvent was partly removed in vacuo, the resultant suspension
was dissolved in 50 mL CHCl3, washed with water (2 x 50 mL),
and dried on Na2SO4 anh. The solvent was partly removed in
vacuo, diluted with MeOH and the solid was filtered, washed on
the filter with Et2O and the obtained pyrrolo[1,2-a]quinoxaline 6
recrystallized from CHCl3/Et2O. The filtrate was concentrated in
vacuo to dryness, triturated with MeOH and the insoluble part
1-(4-Methoxybenzoyl)-3-acetyl-4-benzyl-4H-pyrrolo[1,2-
a]benzimidazole (5c). Pale yellow crystals, mp 130-132 ºC
(CHCl3/MeOH). FT-IR (νmax, cm-1) 1650, 1615, 1605, 1551,
1498, 1447, 1303, 1255, 1208, 1172, 1146, 1114. 1H NMR
(CDCl3) δ (ppm): 2.45 (3H, s, CH3), 3.92 (3H, s, CH3), 6.23 (2H,
s, CH2), 7.04 (2H, d, J 8.0 Hz, H-3’), 7.22-7.33 (8H, m, aromatic
rings), 7.43 (1H, s, H-2), 7.93 (2H, d, J 8.4 Hz, H-2’), 8.83 (1H,
d, J 7.2 Hz, H-8). The individual chemical shifts, multiplicities
and coupling constants for the 7.22-7.33 ppm multiplet were
obtained from undecoupled HSQC as follows: 7.22 (2H, d, J 7.6
Hz, H-2”), 7.23 (1H, t, J 7.3 Hz, H-4”), 7.27 (2H, t, J 7.4 Hz, H-
3”), 7.31 (1H, t, J 6.9 Hz, H-7), 7.33 (1H, d, J 8.2 Hz, H-5), 7.34
(1H, t, J 7.9 Hz, H-6). 13C NMR (CDCl3) δ (ppm): 27.6 (CH3),
49.2 (CH2), 55.5 (OCH3), 103.7 (C-3), 110.7 (C-5), 113.7 (C-3’),
117.2 (C-8), 121.2 (C-1), 121.9 (C-7), 124.6 (C-6), 126.9 (C-2”),
127.2 (C-8a), 127.6 (C-4”), 128.7 (C-3”), 129.6 (C-2), 131.2 (C-

ACCEPTED MANUSCRIPT
2’), 131.8 (C-1’), 136.3 (C-4a), 137.9 (C-1”), 143.5 (C-3a), 162.6
143.9 (C-3a), 163.4 (COO), 183.3 (CO). 15N NMR (CDCl3) δ
(ppm): 118.6 (N-4), 173.8 (N-9), 366.7 (NO2). Anal. Calcd. for
C27H22N2O3 (422.47): C, 76.76; H, 5.25; N, 6.63%. Found: C,
76.81; H, 5.29; N, 6.57%.
(C-4’), 182.5 (CO), 191.2 (COCH3). 15N NMR (CDCl3) δ (ppm):
122.0 (N-4), 174.8 (N-9). Anal. Calcd. for C27H22N2O3 (422.47):
C, 76.76; H, 5.25; N, 6.63%. Found: C, 76.69; H, 5.30; N, 6.56%.
1-(3-Nitrobenzoyl)-3-acetyl-4-benzyl-4H-pyrrolo[1,2-
Ethyl
1-(4-fluorobenzoyl)-4-benzyl-4H-pyrrolo[1,2-
a]benzimidazole (5d). Yellow crystals, mp 209-211 ºC
a]benzimidazole-3-carboxylate (5g). Pale yellow crystals, mp
182-183 ºC (CHCl3/MeOH). FT-IR (νmax, cm-1) 1692, 1623,
1579, 1493, 1451, 1393, 1306, 1234, 1202, 1149, 1115, 1082. 1H
NMR (CDCl3) δ (ppm): 1.29 (3H, t, J 7.2 Hz, CH3-Et), 4.27 (2H,
q, J 7.1 Hz, CH2-Et), 6.11 (2H, bs, CH2), 7.20 (2H, t, J 8.7 Hz, H-
3’), 7.22-7.34 (8H, m, aromatic rings), 7.51 (1H, s, H-2), 7.93
(2H, dd, J 8.7, 5.5 Hz, H-2’), 8.87 (1H, d, J 6.8 Hz, H-8). The
individual chemical shifts, multiplicities and coupling constants
for the 7.22-7.34 ppm multiplet were obtained from undecoupled
HSQC as follows: 7.22 (2H, d, J 7.3 Hz, H-2”), 7.23 (1H, t, J 7.4
Hz, H-4”), 7.26 (1H, d, J 8.1 Hz, H-5), 7.27 (2H, t, J 7.5 Hz, H-
3”), 7.28 (1H, t, J 8.1 Hz, H-7), 7.31 (1H, t, J 8.1 Hz, H-6). 13C
NMR (CDCl3) δ (ppm): 14.4 (CH3-Et), 48.6 (CH2), 60.2 (CH2-
Et), 93.5 (C-3), 110.4 (C-5), 115.4 (d, JC-F 22.1 Hz, C-3’), 117.1
(C-8), 121.0 (C-1), 121.7 (C-7), 124.5 (C-6), 126.7 (C-2”), 127.3
(C-8a), 127.7 (C-4”), 128.8 (C-3”), 130.3 (C-2), 131.4 (d, JC-F 9.1
Hz, C-2’), 135.6 (d, JC-F 3 Hz, C-1’), 136.3 (C-4a), 136.6 (C-1”),
143.9 (C-3a), 163.4 (COO), 164.8 (d, JC-F 251.5 Hz, C-4’), 181.8
(CO). 15N NMR (CDCl3) δ (ppm): 118.9 (N-4), 173.9 (N-9). 19F
NMR (CDCl3) δ (ppm): -108.0. Anal. Calcd. for C27H21FN2O3
(440.47): C, 73.62; H, 4.81; N, 6.36%. Found: C, 73.73; H, 4.90;
N, 6.25%
(CHCl3/MeOH). FT-IR (νmax, cm-1) 1648, 1605, 1548, 1527,
1
1499, 1451, 1352, 1302, 1205, 1150. H NMR (CDCl3) δ (ppm):
2.50 (3H, s, CH3), 6.29 (2H, bs, CH2), 7.25-7.43 (8H, m,
aromatic rings), 7.44 (1H, s, H-2), 7.79 (1H, t, J 8.0 Hz, H-3’),
8.26 (1H, dt, 7.7, J 1.3 Hz, H-2’), 8.49 (1H, ddd, J 8.2, 2.2, 1.0
Hz, H-4’), 8.78 (1H, t, J 1.8 Hz, H-6’), 8.96 (1H, d, J 7.4 Hz, H-
8). The individual chemical shifts, multiplicities and coupling
constants for the 7.25-7.43 ppm multiplet were obtained from
undecoupled HSQC as follows: 7.22 (2H, d, J 7.4 Hz, H-2”),
7.24 (1H, t, J 7.3 Hz, H-4”), 7.28 (2H, t, J 7.5 Hz, H-3”), 7.35
(1H, t, J 7.8 Hz, H-7), 7.38 (1H, d, J 8.1 Hz, H-5), 7.39 (1H, t, J
8.1 Hz, H-6). 13C NMR (CDCl3) δ (ppm): 27.6 (CH3), 49.4
(CH2), 104.9 (C-3), 110.9 (C-5), 117.2 (C-8), 120.4 (C-1), 122.2
(C-7), 123.8 (C-6’), 125.0 (C-6), 125.8 (C-4’), 126.8 (C-2”),
127.1 (C-8a), 127.7 (C-4”), 128.8 (C-3”), 129.7 (C-3’), 130.7 (C-
2), 134.5 (C-2’), 136.3 (C-4a), 136.6 (C-1”), 141.0 (C-1’), 143.9
(C-3a), 148.1 (C-5’), 180.1 (CO), 191.3 (CO-3). 15N NMR
(CDCl3) δ (ppm): 118.9 (N-4), 173.9 (N-9). Anal. Calcd. for
C26H19N3O4 (437.45): C, 71.39; H, 4.38; N, 9.61%. Found: C,
71.21; H, 4.29; N, 9.72%.
1-(4-Nitrobenzoyl)-3-acetyl-4-benzyl-4H-pyrrolo[1,2-
a]benzimidazole (5e). Yellow crystals, mp 232-234 ºC (CHCl3).
FT-IR (νmax, cm-1) 1651, 1618, 1595, 1555, 1524, 1496, 1349,
1296, 1201, 1160. 1H NMR (CDCl3) δ (ppm): 2.45 (3H, s, CH3),
6.23 (2H, s, CH2), 7.20-7.38 (9H, m, aromatic rings), 8.02 (2H, d,
J 8.0 Hz, H-2’), 8.38 (2H, d, J 8.0 Hz, H-3’), 8.94 (1H, d, J 7.6
Hz, H-8). The individual chemical shifts, multiplicities and
coupling constants for the 7.20-7.38 ppm multiplet were obtained
from undecoupled HSQC as follows: 7.20 (2H, d, J 7.4 Hz, H-
2”), 7.23 (1H, t, J 7.5 Hz, H-4”), 7.26 (2H, t, J 7.5 Hz, H-3”),
7.35 (1H, t, J 7.6 Hz, H-7), 7.36 (1H, s, H-2), 7.37 (1H, d, J 8.0
Hz, H-5), 7.38 (1H, t, J 7.8 Hz, H-6). 13C NMR (CDCl3) δ (ppm):
27.6 (CH3), 49.4 (CH2), 105.0 (C-3), 111.0 (C-5), 117.3 (C-8),
120.7 (C-1), 122.3 (C-7), 123.7 (C-3’), 125.1 (C-6), 126.9 (C-
2”), 127.2 (C-8a), 127.8 (C-4”), 128.8 (C-3”), 129.8 (C-2’),
131.0 (C-2), 136.3 (C-4a), 136.7 (C-1”), 143.9 (C-3a), 145.2 (C-
1’), 149.4 (C-4’), 180.6 (CO), 191.1 (COCH3). 15N NMR
(CDCl3) δ (ppm): 123.2 (N-4), 173.4 (N-9), 366.7 (NO2). Anal.
Calcd. for C26H19N3O4 (437.45): C, 71.39; H, 4.38; N, 9.61%.
Found: C, 71.45; H, 4.34; N, 9.66%.
Ethyl
1-(4-nitrobenzoyl)-4-benzyl-4H-pyrrolo[1,2-
a]benzimidazole-3-carboxylate (5i). Yellow crystals, mp 210-212
ºC (CHCl3/MeOH). FT-IR (νmax, cm-1) 1691, 1627, 1598, 1578,
1
1520, 1499, 1451, 1349, 1307, 1202, 1156, 1116, 1084. H NMR
(CDCl3) δ (ppm): 1.29 (3H, t, J 7.1 Hz, CH3-Et), 4.27 (2H, q, J
7.0 Hz, CH2-Et), 6.13 (2H, s, CH2), 7.23-7.36 (8H, m, aromatic
rings), 7.47 (1H, s, H-2), 8.02 (2H, d, J 8.4 Hz, H-2’), 8.37 (2H,
d, J 8.4 Hz, H-3’), 8.95 (1H, d, J 7.08 Hz, H-8). The individual
chemical shifts, multiplicities and coupling constants for the
7.23-7.36 ppm multiplet were obtained from undecoupled HSQC
as follows: 7.28 (2H, d, J 7.40 Hz, H-2”), 7.30 (1H, t, J 7.60 Hz,
H-4”), 7.34 (2H, t, J 7.60 Hz, H-3”), 7.36 (1H, d, J 8.1 Hz, H-5),
7.38 (1H, t, J 7.64 Hz, H-7), 7.40 (1H, d, J 8.1 Hz, H-6). 13C
NMR (CDCl3) δ (ppm): 14.4 (CH3-Et), 48.7 (CH2), 60.4 (CH2-
Et), 94.6 (C-3), 110.6 (C-5), 117.1 (C-8), 120.7 (C-1), 122.0 (C-
7), 123.6 (C-3’), 124.9 (C-6), 126.8 (C-2”), 127.3 (C-8a), 127.82
(C-4”), 128.85 (C-3”), 129.8 (C-2’), 131.2 (C-2), 136.2 (C-4a),
136.4 (C-1”), 144.1 (C-3a), 145.2 (C-1’), 149.3 (C-4’), 163.1
(COO), 180.5 (CO). 15N NMR (CDCl3) δ (ppm):120.1 (N-4),
173.7 (N-9), 367.1 (NO2). Anal. Calcd. for C27H21N3O5 (467.47):
C, 69.37; H, 4.53; N, 8.99%. Found: C, 69.41; H, 4.48; N, 9.03%.
Ethyl 1-benzoyl-4-benzyl-4H-pyrrolo[1,2-a]benzimidazole-3-
carboxylate (5f). Pale yellow crystals, mp 190-192 ºC
(CHCl3/MeOH). FT-IR (νmax, cm-1) 1689, 1619, 1578, 1500,
1451, 1391, 1307, 1234, 1202, 1153, 1115, 1083. 1H NMR
(CDCl3) δ (ppm): 1.33 (3H, t, J 7.2 Hz, CH3-Et), 4.31 (2H, q, J
7.2 Hz, CH2-Et), 6.17 (2H, s, CH2), 7.30-7.39 (8H, m, aromatic
rings), 7.57 (2H, t, J 7.1 Hz, H-3’), 7.59 (1H, s, H-2), 7.64 (1H, t,
J 7.7 Hz, H-4’), 7.96 (2H, d, J 7.2 Hz, H-2’), 8.98 (1H, d, J 6.9
Hz, H-8). The individual chemical shifts, multiplicities and
coupling constants for the 7.30-7.39 ppm multiplet were obtained
from undecoupled HSQC as follows: 7.28 (1H, t, J 8.2 Hz, H-
4”), 7.29 (2H, d, J 8.0 Hz, H-2”), 7.32 (1H, d, J 8.2 Hz, H-5),
7.33 (2H, t, J 7.8 Hz, H-3”), 7.34 (1H, t, J 8.1 Hz, H-7), 7.37
(1H, t, J 8.2 Hz, H-6). 13C NMR (CDCl3) δ (ppm): 14.4 (CH3-Et),
48.6 (CH2), 60.1 (CH2-Et), 93.4 (C-3), 110.3 (C-5), 117.2 (C-8),
121.3 (C-1), 121.7 (C-7), 124.5 (C-6), 126.8 (C-2”), 127.4 (C-
8a), 127.7 (C-4”), 128.3 (C-3’), 128.8 (C-3”), 129.1 (C-2’), 130.5
(C-2), 131.4 (C-4’), 136.3 (C-4a), 136.6 (C-1”), 139.5 (C-1’),
1-(4-Nitrobenzoyl)-3-acetyl-4-ethyl-6,7-dimethyl-4H-
pyrrolo[1,2-a]benzimidazole (5j). Yellow crystals, mp 304-306
ºC (CHCl3). FT-IR (νmax, cm-1) 1655, 1611, 1591, 1547, 1521,
1498, 1348, 1314, 1279, 1220, 1186, 1151. 1H NMR
(CDCl3+TFA) δ (ppm): 1.48 (3H, t, J 6.6 Hz, CH3-Et), 2.46 (3H,
s, CH3-7), 2.47 (3H, s, CH3-6), 2.57 (3H, s, CH3), 4.87 (2H, q, J
6.8 Hz, CH2-Et), 7.30 (1H, s, CH-5), 7.42 (1H, s, H-2), 8.00 (2H,
d, J 8.1 Hz, H-2’), 8.43 (2H, d, J 8.1 Hz, H-3’), 8.56 (1H, s, H-8).
13C NMR (CDCl3+TFA) δ (ppm): 15.4 (CH3-Et), 20.2 (CH3-7),
20.6 (CH3-6), 25.7 (CH3), 41.7 (CH2-Et), 106.0 (C-3), 111.0 (C-
5), 117.4 (C-8), 122.0 (C-1), 124.1 (C-3’), 125.3 (C-8a), 130.0
(C-2’), 133.2 (C-7), 134.0 (C-4a), 134.8 (C-2), 135.7 (C-6),
143.3 (C-1’), 143.7 (C-3a), 149.9 (C-4’), 182.2 (CO), 194.5 (CO-
CH3). 15N NMR (CDCl3+TFA) δ (ppm): 130.6 (N-4), 173.3 (N-
9), 366.20 (NO2). Anal. Calcd. for C23H21N3O4 (403.43): C,
68.47; H, 5.25; N, 10.42%. Found: C, 68.41; H, 5.19; N, 10.47%.

10
Tetrahedron
ACCEPTED MANUSCRIPT
Ethyl
1-(4-chlorobenzoyl)-4-ethyl-6,7-dimethyl-4H-
Hz, H-2”), 7.26 (1H, t, J 7.4 Hz, H-4”), 7.30 (2H, t, J 7.6 Hz, H-
3”). 13C NMR (CDCl3) δ (ppm): 14.4 (CH3-Et), 20.2 (CH3-7),
20.5 (CH3-6), 21.6 (CH3), 48.4 (CH2), 60.0 (CH2-Et), 93.3 (C-3),
110.7 (C-5), 117.4 (C-8), 121.1 (C-1), 125.8 (C-8a), 126.6 (C-
2”), 127.5 (C-4”), 128.7 (C-3”), 129.0 (C-3’), 129.2 (C-2’), 129.9
(C-2), 130.6 (C-7), 133.4 (C-6), 134.7 (C-4a), 136.8 (C-1’),
137.0 (C-1”), 141.9 (C-4’), 143.7 (C-3a), 163.5 (COO), 183.2
(CO). 15N NMR (CDCl3) δ (ppm): 117.1 (N-4), 173.4 (N-9).
Anal. Calcd. for C30H28N2O3 (464.55): C, 77.56; H, 6.07; N,
6.03%. Found: C, 77.68; H, 6.19; N, 5.97%.
pyrrolo[1,2-a]benzimidazole-3-carboxylate (5k). Pale yellow
crystals, mp 173-175 ºC (CHCl3/MeOH). FT-IR (νmax, cm-1)
2969, 2935, 1697, 1627, 1580, 1506, 1451, 1382, 1310, 1281,
1220, 1171, 1091. 1H NMR (CDCl3) δ (ppm): 1.36 (3H, t, J 7.1
Hz, CH3-3), 1.46 (3H, t, J 7.1 Hz, CH3-Et), 2.43 (6H, s, CH3-6
and CH3-7), 4.31 (2H, q, J 7.1 Hz, CH2-3), 4.81 (2H, q, J 7.1 Hz,
CH2-Et), 7.15 (1H, s, H-5), 7.43 (1H, s, H-2), 7.49 (2H, d, J 8.4
Hz, H-3’), 7.83 (2H, d, J 8.4 Hz, H-3’), 8.64 (1H, s, H-8). 13C
NMR (CDCl3) δ (ppm): 14.5 (CH3-3), 14.9 (CH3-Et), 20.2 (CH3-
7), 20.5 (CH3-6), 40.1 (CH2-Et), 60.0 (CH2-3), 93.6 (C-3), 109.9
(C-5), 117.4 (C-8), 120.7 (C-1), 125.7 (C-8a), 128.6 (C-3’),
130.3 (C-2), 130.4 (C-7), 130.4 (C-2’), 133.5 (C-6), 134.3 (C-
4a), 137.4 (C-4’), 138.1 (C-1’), 143.3 (C-3a), 163.3 (COO),
181.6 (CO). 15N NMR (CDCl3) δ (ppm): 122.1 (N-4), 173.3 (N-
9). Anal. Calcd. for C24H23ClN2O3 (422.90): C, 68.16; H, 5.48; N,
6.62%. Found: C, 68.22; H, 5.51; N, 6.55%.
Ethyl
1-(4-nitrobenzoyl)-4-benzyl-6,7-dimethyl-4H-
(5o). Yellow
pyrrolo[1,2-a]benzimidazole-3-carboxylate
crystals, mp 221-223 ºC (CHCl3). FT-IR (νmax, cm-1) 1686, 1620,
1568, 1520, 1493, 1452, 1349, 1311, 1222, 1171, 1145, 1118,
1080. 1H NMR (CDCl3) δ (ppm): 1.27 (3H, t, J 6.8 Hz, CH3-Et),
2.35 (3H, s, CH3-6), 2.42 (3H, s, CH3-7), 4.25 (2H, q, J 6.8 Hz,
CH2-Et), 6.07 (2H, bs, CH2), 7.07 (1H, s, CH-5), 7.21 (2H, d, J
6.8 Hz, H-2”), 7.27 (1H, t, J 6.6 Hz, H-4”), 7.30 (2H, t, J 6.6 Hz,
H-3”), 7.42 (1H, s, H-2), 8.02 (2H, d, J 8.6 Hz, H-2’), 8.37 (2H,
d, J 8.6 Hz, H-3’), 8.69 (1H, s, H-8). 13C NMR (CDCl3) δ (ppm):
14.4 (CH3-Et), 20.3 (CH3-7), 20.5 (CH3-6), 48.5 (CH2), 60.3
(CH2-Et), 94.8 (C-3), 110.9 (C-5), 117.4 (C-8), 120.5 (C-1),
123.6 (C-3’), 125.8 (C-8a), 126.6 (C-2”), 127.7 (C-4”), 128.8 (C-
3”), 129.8 (C-2’), 131.0 (C-2), 131.1 (C-7), 134.0 (C-6), 134.7
(C-4a), 136.7 (C-1”), 143.9 (C-3a), 145.4 (C-1’), 149.3 (C-4’),
163.1 (COO), 180.4 (CO). 15N NMR (CDCl3) δ (ppm): 117.3 (N-
4), 172.4 (N-9), 367.0 (NO2). Anal. Calcd. for C29H25N3O5
(495.53): C, 70.29; H, 5.08; N, 8.48%. Found: C, 70.33; H, 5.02;
N, 8.53%.
1-Benzoyl-3-acetyl-4-benzyl-6,7-dimethyl-4H-pyrrolo[1,2-
a]benzimidazole (5l). Yellow crystals, mp 233-235 ºC
(CHCl3/MeOH). FT-IR (νmax, cm-1) 1643, 1615, 1548, 1496,
1451, 1397, 1357, 1310, 1223, 1173. 1H NMR (CDCl3) δ (ppm):
2.35 (3H, s, CH3-6), 2.41 (3H, s, CH3-7), 2.42 (3H, s, CH3), 6.18
(2H, s, CH2), 7.09 (1H, s, CH-5), 7.19 (2H, d, J 6.9 Hz, H-2”),
7.24 (1H, t, J 6.8 Hz, H-4”), 7.27 (2H, t, J 6.6 Hz, H-3”), 7.39
(1H, s, H-2), 7.54 (2H, t, J 7.6 Hz, H-3’), 7.60 (1H, t, J 7.3 Hz,
H-4’), 7.91 (2H, d, J 7.0 Hz, H-2’), 8.67 (1H, s, H-8). 13C NMR
(CDCl3) δ (ppm): 20.2 (CH3-7), 20.5 (CH3-6), 27.5 (CH3), 49.1
(CH2), 104.2 (C-3), 111.0 (C-5), 117.5 (C-8), 121.0 (C-1), 125.6
(C-8a), 126.7 (C-2”), 127.5 (C-4”), 128.4 (C-3’), 128.7 (C-3”),
129.0 (C-2’), 130.3 (C-2), 131.0 (C-7), 131.4 (C-4’), 133.9 (C-6),
134.7 (C-4a), 137.2 (C-1”), 139.5 (C-1’), 143.4 (C-3a), 183.3
(CO), 191.1 (COCH3). 15N NMR (CDCl3) δ (ppm): 120.4 (N-4),
173.0 (N-9). Anal. Calcd. for C28H24N2O2 (420.50): C, 79.98; H,
5.75; N, 6.66%. Found: C, 80.03; H, 5.71; N, 6.60%.
2-Acetyl-4-hydroxy-4-(4-chlorophenyl)-5-benzyl-4,5-
dihydropyrrolo[1,2-a]quinoxaline (6b). Pale brown crystals, mp
157-159 ºC (MeOH). FT-IR (νmax, cm-1) 3238, 1635, 1610, 1547,
1521, 1492, 1354, 1333, 1261, 1195, 1168, 1090. 1H NMR
(DMSO) δ (ppm): 2.40 (3H, s, CH3), 4.24 (1H, d, J 17.2 Hz,
A
B
Ethyl
1-benzoyl-4-benzyl-6,7-dimethyl-4H-pyrrolo[1,2-
CH2 ), 4.49 (1H, d, J 17.2 Hz, CH2 ), 5.94 (1H, d, J 1.6 Hz, H-
3), 6.61 (1H, d, J 7.6 Hz, H-6), 6.92 (1H, t, J 6.7 Hz, H-8), 7.02
(1H, t, J 7.0 Hz, H-7), 7.17 (1H, t, J 7.2 Hz, H-4”), 7.23 (1H, s,
OH), 7.25 (2H, t, J 7.2 Hz, H-3”), 7.31 (2H, d, J 7.2 Hz, H-2”),
7.39 (2H, d, J 8.8 Hz, H-3’), 7.58 (2H, d, J 8.4 Hz, H-2’), 7.92
(1H, d, J 8.0 Hz, H-9), 8.50 (1H, d, J 1.6 Hz, H-1). 13C NMR
(DMSO) δ (ppm): 27.0 (CH3), 48.4 (CH2), 84.2 (C-4), 105.8 (C-
3), 115.4 (C-9), 115.6 (C-6), 118.8 (C-8), 119.4 (C-1), 123.7 (C-
9a), 126.1 (C-7), 126.2 (C-2” and C-2), 126.5 (C-4”), 128.0 (C-
3’), 128.3 (C-3”), 128.4 (C-2’), 132.6 (C-1’), 133.7 (C-3a), 135.0
(C-5a), 138.2 (C-1”), 142.7 (C-4’), 192.5 (CO). 15N NMR
(DMSO) δ (ppm): 87.9 (N-5), 170.5 (N-10). Anal. Calcd. for
C26H21ClN2O2 (428.91): C, 72.81; H, 4.93; N, 6.53%. Found: C,
72.78; H, 4.97; N, 6.61%.
a]benzimidazole-3-carboxylate (5m). Yellow crystals, mp 208-
209 ºC (CHCl3/MeOH). FT-IR (νmax, cm-1) 1690, 1613, 1561,
1
1496, 1449, 1223, 1314, 1153, 1113, 1082. H NMR (CDCl3) δ
(ppm): 1.31 (3H, t, J 7.2 Hz, CH3-Et), 2.38 (3H, s, CH3-6), 2.45
(3H, s, CH3-7), 4.29 (2H, q, J 6.8 Hz, CH2-Et), 6.10 (2H, s, CH2),
7.07 (1H, s, CH-5), 7.27 (2H, d, J 6.9 Hz, H-2”), 7.30 (1H, t, J
5.4 Hz, H-4”), 7.34 (2H, t, J 6.6 Hz, H-3”), 7.55 (1H, s, H-2),
7.57 (2H, t, J 7.6 Hz, H-3’), 7.63 (1H, t, J 7.1 Hz, H-4’), 7.96
(2H, d, J 6.9 Hz, H-2’), 8.73 (1H, s, H-8). 13C NMR (CDCl3) δ
(ppm): 14.4 (CH3-Et), 20.2 (CH3-7), 20.5 (CH3-6), 48.4 (CH2),
60.0 (CH2-Et), 93.5 (C-3), 110.7 (C-5), 117.4 (C-8), 121.1 (C-1),
125.8 (C-8a), 126.6 (C-2”), 127.5 (C-4”), 128.3 (C-3’), 128.7 (C-
3”), 129.1 (C-2’), 130.3 (C-2), 130.6 (C-7), 131.3 (C-4’), 133.5
(C-6), 134.7 (C-4a), 136.9 (C-1”), 139.5 (C-1’), 143.7 (C-3a),
163.4 (COO), 183.2 (CO). 15N NMR (CDCl3) δ (ppm): 117.4 (N-
4), 173.4 (N-9). Anal. Calcd. for C29H26N2O3 (450.53): C, 77.31;
H, 5.78; N, 6.22%. Found: C, 77.35; H, 5.84; N, 6.18%.
2-Acetyl-4-hydroxy-4-(3-nitrophenyl)-5-benzyl-4,5-
diydropyrrolo[1,2-a]quinoxaline (6d). Orange crystals, mp 168-
170 ºC (CHCl3/MeOH). FT-IR (νmax, cm-1): 3312, 1641, 1612,
1
1518, 1496, 1450, 1346, 1258, 1191, 1088. H NMR (DMSO) δ
A
Ethyl
1-(4-methylbenzoyl)-4-benzyl-6,7-dimethyl-4H-
(ppm): 2.40 (3H, s, CH3), 4.26 (1H, d, J 17.6 Hz, CH2 ), 4.53
B
pyrrolo[1,2-a]benzimidazole-3-carboxylate
(5n).
Yellow
(1H, d, J 17.2 Hz, CH2 ), 5.97 (1H, d, J 2 Hz, H-3), 6.67 (1H, dd,
crystals, mp 188-190 ºC (CHCl3/MeOH). FT-IR (νmax, cm-1)
J 8.4, 0.8 Hz, H-6), 6.96 (1H, td, J 8.0, 1.2 Hz, H-8), 7.06 (1H,
td, J 8.4, 1.2 Hz, H-7), 7.16 (1H, t, J 7.2 Hz, H-4”), 7.23 (2H, t, J
7.2 Hz, H-3”), 7.29 (2H, d, J 7.2 Hz, H-2”), 7.54 (1H, bs, OH),
7.61 (1H, t, J 8.0 Hz, H-5’), 7.98 (2H, d, J 8.0 Hz, H-6’ and H-9),
8.17 (1H, ddd, J 8.4, 2.4, 1.2 Hz, H-4’), 8.46 (1H, t, J 2.0 Hz, H-
2’), 8.55 (1H, d, J 1.6 Hz, H-1). 13C NMR (DMSO) δ (ppm): 27.0
(CH3), 48.5 (CH2), 84.0 (C-4), 106.2 (C-3), 115.5 (C-9), 115.7
(C-6), 119.0 (C-8), 119.6 (C-1), 121.2 (C-2’), 123.1 (C-4’), 123.6
(C-9a), 126.1 (C-2”), 126.2 (C-7), 126.58 (C-4”), 126.64 (C-2),
128.3 (C-3”), 129.8 (C-5’), 133.0 (C-3a), 133.3 (C-6’), 134.8 (C-
1691, 1604, 1573, 1494, 1452, 1363, 1310, 1273, 1220, 1168,
1
1114, 1079. H NMR (CDCl3) δ (ppm): 1.26 (3H, t, J 7.2 Hz,
CH3-Et), 2.32 (3H, s, CH3-6), 2.39 (3H, s, CH3-7), 2.47 (3H, s,
CH3), 4.24 (2H, q, J 7.2 Hz, CH2-Et), 6.05 (2H, s, CH2), 7.02
(1H, s, CH-5), 7.21-7.28 (5H, m, aromatic ring), 7.32 (2H, d, J
7.8 Hz, H-3’), 7.50 (1H, s, H-2), 7.82 (2H, t, J 7.8 Hz, H-2’),
8.65 (1H, s, H-8). The individual chemical shifts, multiplicities
and coupling constants for the 7.21-7.28 ppm multiplet were
obtained from undecoupled HSQC as follows: 7.24 (2H, d, J 7.4

ACCEPTED MANUSCRIPT
5a), 138.0 (C-1”), 145.9 (C-1’), 147.4 (C-5’), 192.5 (CO). 15N
Ethyl
4-hydroxy-4-(4-nitrophenyl)-5-benzyl-4,5-
NMR (DMSO) δ (ppm): 87.6 (N-5), 169.9 (N-10) and 369.7
(NO2). Anal. Calcd. for C26H21N3O4 (439.46): C, 71.06; H, 4.82;
N, 9.56%. Found: C, 71.10; H, 4.77; N, 9.62%.
dihydropyrrolo[1,2-a]quinoxaline-2-carboxylate (6i). Pale brown
crystals, mp 176-178 ºC (MeOH). FT-IR (νm1ax, cm-1) 3318, 1700,
1668, 1558, 1520, 1454, 1347, 1274, 1196. H NMR (DMSO) δ
(ppm): 1.25 (3H, t, J 7.2 Hz, CH3-Et), 4.14-4.27 (2H, m, CH2-Et),
Ethyl
4-hydroxy-4-(4-fluorophenyl)-5-benzyl-4,5-
A
B
4.21 (1H, d, J 16.6 Hz, CH2 ), 4.52 (1H, d, J 17.3 Hz, CH2 ),
5.96 (1H, d, J 1.70 Hz, H-3), 6.62 (1H, dd, J 8.4, 0.8 Hz, H-6),
6.91 (1H, td, J 8.0, 1.0 Hz, H-8), 7.03 (1H, td, J 8.4, 1.4 Hz, H-
7), 7.14 (1H, t, J 7.2 Hz, H-4”), 7.25 (2H, t, J 7.2 Hz, H-3”), 7.31
(2H, d, J 7.3 Hz, H-2”), 7.52 (1H, s, OH), 7.84 (2H, d, J 9.0 Hz,
H-2’), 7.99 (1H, dd, J 8.1, 1.4 Hz, H-9), 8.20 (2H, d, J 9.0 Hz, H-
3’), 8.36 (1H, d, J 1.7 Hz, H-1). 13C NMR (DMSO) δ (ppm): 14.3
(CH3-Et), 48.4 (CH2), 59.4 (CH2-Et), 84.1 (C-4), 107.4 (C-3),
115.4 (C-6), 115.6 (C-9), 117.2 (C-2), 118.6 (C-1), 118.9 (C-8),
123.2 (C-3’), 123.3 (C-9a), 126.09 (C-7), 126.14 (C-2”), 126.5
(C-4”), 127.8 (C-2’), 128.2 (C-3”), 132.3 (C-3a), 134.5 (C-5a),
138.0 (C-1”), 147.1 (C-4’), 150.7 (C-1’), 163.3 (COO). 15N NMR
(DMSO) δ (ppm): 85.7 (N-5), 170.1 (N-10), 369.2 (NO2). Anal.
Calcd. for C27H23N3O5 (469.49): C, 69.07; H, 4.94; N, 8.95%.
Found: C, 68.99; H, 4.91; N, 9.03%.
dihydropyrrolo[1,2-a]quinoxaline-2-carboxylate
(6g).
Pale
brown crystals, mp 157-159 ºC (MeOH). FT-IR (νmax, cm-1) 3332,
1704, 1670, 1605, 1524, 1450, 1388, 1273, 1206, 1154. 1H NMR
(DMSO) δ (ppm): 1.26 (3H, t, J 7.2 Hz, CH3-Et), 4.14-4.27 (2H,
A
m, CH2-Et), 4.28 (1H, d, J 17.4 Hz, CH2 ), 4.48 (1H, d, J 17.2
B
Hz, CH2 ), 5.90 (1H, d, J 1.6 Hz, H-3), 6.61 (1H, dd, J 8.3, 0.9
Hz, H-6), 6.89 (1H, td, J 8.0, 1.1 Hz, H-8), 7.00 (1H, td, J 7.5,
1.4 Hz, H-7), 7.13-7.18 (3H, m, aromatic rings), 7.14 (1H, s,
OH), 7.24 (2H, t, J 7.7 Hz, H-3”), 7.30 (2H, d, J 7.2 Hz, H-2”),
7.63 (2H, dd, J 8.9, 5.5 Hz, H-2’), 7.94 (1H, dd, J 8.0, 1.4 Hz, H-
9), 8.30 (1H, d, J 1.7 Hz, H-1). The individual chemical shifts,
multiplicities and coupling constants for the 7.13-7.18 ppm
multiplet were obtained from undecoupled HSQC as follows:
7.16 (2H, t, J 8.9 Hz, H-3’), 7.17 (1H, t, J 7.1 Hz, H-4”). 13C
NMR (DMSO) δ (ppm): 14.3 (CH3-Et), 48.3 (CH2), 59.4 (CH2-
Et), 84.2 (C-4), 106.9 (C-3), 114.7 (d, JC-F 22.1 Hz, C-3’), 115.5
(C-9), 115.6 (C-6), 116.9 (C-2), 118.4 (C-1), 118.7 (C-8), 123.7
(C-9a), 126.0 (C-7), 126.1 (C-2”), 126.5 (C-4”), 128.3 (C-3”),
128.7 (d, JC-F 8.1 Hz, C-2’), 133.4 (C-3a), 134.9 (C-5a), 138.2
(C-1”), 139.8 (d, JC-F 2.4 Hz, C-1’), 161.6 (d, JC-F 244.5 Hz, C-
4’), 163.5 (COO). 15N NMR (DMSO) δ (ppm): 88.6 (N-5), 170.8
(N-10). 19F NMR (CDCl3) δ (ppm): -114.6. Anal. Calcd. for
C27H23FN2O3 (442.48): C, 73.29; H, 5.24; N, 6.33%. Found: C,
73.22; H, 5.31; N, 6.37%. Single crystal X-ray:
C29H28.5BrFN2.75O3.75, Mr = 574.46 g mol-1, size 0.200.200.10
mm3, triclinic, space group P-1, a 11.2429(4) Å, b = 11.4012(5)
Å, c = 12.1351(5) Å, α = 99.621(3),  = 93.444(3), γ
107.593(4)°, V = 1451.73(10) Å3, Z = 2, ρcalcd = 1.314 g cm-3,
μ(MoKα) = 1.457 mm-1, F(000) = 592, 20650 reflections in h(-
13/13), k(-13/13), l(-14/14), measured in the range 5.8  Θ 
50.06, T = 200 K, completeness Θmax = 99.92%, 5086
independent reflections, Rint = 0.0373, 345 parameters, 7
2-Acetyl-4-hydroxy-4-(4-nitrophenyl)-5-ethyl-7,8-dimethyl-
4,5-dihydropyrrolo[1,2-a]quinoxaline (6j). Orange crystals, mp
196-198 ºC (MeOH). FT-IR (νmax, cm-1) 3111, 2986, 1680, 1594,
1522, 1501, 1452, 1366, 1348, 1280, 1196. 1H NMR (DMSO) δ
(ppm): 1.05 (3H, t, J 6.9 Hz, CH3-Et), 2.26 (3H, s, CH3-8), 2.27
(3H, s, CH3-7), 2.35 (3H, s, CH3), 3.11 (1H, dq, J 14.80, 7.20 Hz,
A
B
CH2 ), 3.24 (1H, dq, J 14.70, 7.0 Hz, CH2 ), 5.86 (1H, d, J 2.0
Hz, H-3), 6.78 (1H, s, H-6), 7.11 (1H, s, OH), 7.74 (2H, d, J 8.8
Hz, H-2’), 7.74 (1H, s, H-9), 8.25 (2H, d, J 8.8 Hz, H-3’), 8.40
(1H, d, J 1.6 Hz, H-1). 13C NMR (DMSO) δ (ppm): 13.5 (CH3-
Et), 18.4 (CH3-8), 19.6 (CH3-7), 26.9 (CH3), 39.3 (CH2), 83.9 (C-
4), 105.5 (C-3), 115.0 (C-6), 116.5 (C-9), 118.8 (C-1), 120.7 (C-
9a), 123.3 (C-3’), 125.9 (C-8), 126.3 (C-2), 127.8 (C-2’), 132.1
(C-5a), 132.8 (C-3a), 134.4 (C-7), 146.9 (C-4’), 151.5 (C-1’),
192.4 (CO). 15N NMR (DMSO) δ (ppm): 87.2 (N-5), 170.4 (N-
10) and 369.5 (NO2). Anal. Calcd. for C23H23N3O4 (405.45): C,
68.13; H, 5.72; N, 10.36%. Found: C, 68.21; H, 5.80; N, 10.25%.
restraints, R1obs=0.0592, wR2obs = 0.1529, R1all = 0.0721, wR2all
0.1618, GoF = 1.049, largest difference peak and hole: 0.85/-0.61
A-3. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK). CCDC: 1431562.
=
Ethyl 4-hydroxy-4-(4-chlorophenyl)-5-ethyl-7,8-dimethyl-4,5-
dihydropyrrolo[1,2-a]quinoxaline-2-carboxylate (6k). Colourless
crystals, mp 154-156 ºC (CHCl3/MeOH). FT-IR (νmax, cm-1):
3336, 2976, 2934, 1677, 1555, 1526, 1491, 1387, 1335, 1263,
e
1
1201, 1167, 1090. H NMR (DMSO) δ (ppm): 1.03 (3H, t, J 6.9
Hz, CH3-Et-5), 1.24 (3H, t, J 7.2 Hz, CH3-Et-2), 2.23 (3H, s,
CH3-8), 2.25 (3H, s, CH3-7), 3.11 (1H, dq, J 14.30, 7.24 Hz,
Ethyl
4-hydroxy-4-(4-chlorophenyl)-5-benzyl-4,5-
A
B
dihydropyrrolo[1,2-a]quinoxaline-2-carboxylate (6h). Off-white
crystals, mp 170-172 ºC (CHCl3/MeOH). FT-IR (νmax, cm-1)
3332, 1716, 1659, 1611, 1552, 1527, 1493, 1378, 1315, 1268,
1193, 1165, 1091. 1H NMR (DMSO) δ (ppm): 1.28 (3H, t, J 7.2
Hz, CH3-Et), 4.14-4.25 (2H, m, CH2-Et), 4.26 (1H, d, J 17.0 Hz,
CH2 -Et-5), 3.22 (1H, dq, J 14.60, 7.24 Hz, CH2 -Et-5), 4.11-
4.23 (2H, m, CH2-Et-2), 5.78 (1H, d, J 1.7 Hz, H-3), 6.75 (1H, s,
H-6), 6.81 (1H, s, OH), 7.44 (2H, d, J 8.7 Hz, H-3’), 7.51 (2H, d,
J 8.6 Hz, H-2’), 7.75 (1H, s, H-9), 8.16 (1H, d, J 1.7 Hz, H-1).
13C NMR (DMSO) δ (ppm): 13.5 (CH3-Et-5), 14.3 (CH3-Et-2),
18.3 (CH3-8), 19.5 (CH3-7), 38.7 (CH2-Et-5), 59.3 (CH2-Et-2),
83.8 (C-4), 106.4 (C-3), 115.0 (C-6), 116.5 (C-2), 116.6 (C-9),
117.7 (C-1), 120.8 (C-9a), 125.7 (C-8), 127.9 (C-3’), 128.5 (C-
2’), 132.28 (C-5a), 132.30 (C-4’), 133.1 (C-3a), 134.2 (C-7),
143.3 (C-1’), 163.6 (COO). 15N NMR (DMSO) δ (ppm): 88.3 (N-
5), 170.4 (N-10). Anal. Calcd. for C24H25ClN2O3 (424.92): C,
67.84; H, 5.93; N, 6.59%. Found: C, 67.78; H, 6.01; N, 6.55%.
A
B
CH2 ), 4.49 (1H, d, J 17.2 Hz, CH2 ), 5.91 (1H, d, J 0.9 Hz, H-
3), 6.61 (1H, d, J 8.2 Hz, H-6), 6.89 (1H, t, J 7.6 Hz, H-8), 7.01
(1H, t, J 7.6 Hz, H-7), 7.17 (1H, t, J 7.2 Hz, H-4”), 7.20 (1H, s,
OH), 7.25 (2H, t, J 7.2 Hz, H-3”), 7.30 (2H, d, J 7.2 Hz, H-2”),
7.40 (2H, d, J 8.4 Hz, H-3’), 7.60 (2H, d, J 8.4 Hz, H-2’), 7.95
(1H, d, J 7.6 Hz, H-9), 8.31 (1H, d, J 1.2 Hz, H-1). 13C NMR
(DMSO) δ (ppm): 14.3 (CH3-Et), 48.3 (CH2), 59.3 (CH2-Et), 84.1
(C-4), 107.0 (C-3), 115.48 (C-9), 115.51 (C-6), 117.0 (C-2),
118.4 (C-1), 118.7 (C-8), 123.5 (C-9a), 126.0 (C-7), 126.1 (C-
2”), 126.5 (C-4”), 127.9 (C-3’), 128.2 (C-3”), 128.4 (C-2’), 132.5
(C-4’), 133.1 (C-3a), 134.8 (C-5a), 138.1 (C-1”), 142.7 (C-1’),
163.4 (COO). 15N NMR (DMSO) δ (ppm): 87.6 (N-5), 170.0 (N-
10). Anal. Calcd. for C27H23ClN2O3 (458.94): C, 70.66; H, 5.05;
N, 6.10%. Found: C, 70.57; H, 5.11; N, 6.16%.
2-Acetyl-4-hydroxy-4-phenyl-5-benzyl-7,8-dimethyl-4,5-
dihydropyrrolo[1,2-a]quinoxaline (6l). Off-white crystals, mp
165-166 ºC (MeOH). FT-IR (νmax, cm-1): 3381, 2917, 1619, 1513,
1447, 1401, 1350, 1326, 1237, 1197, 1169, 1119. 1H NMR
(DMSO) δ (ppm): 2.01 (3H, s, CH3-7), 2.20 (3H, s, CH3-8), 2.39
A
(3H, s, CH3-CO), 4.21 (1H, d, J 16.8 Hz, CH2 ), 4.49 (1H, d, J
B
16.8 Hz, CH2 ), 5.94 (1H, d, J 1.6 Hz, H-3), 6.43 (1H, s, H-6),
7.03 (1H, s, OH), 7.16 (1H, t, J 7.2 Hz, H-4”), 7.25 (2H, t, J 7.6

12
Tetrahedron
ACCEPTED MANUSCRIPT
Hz, H-3”), 7.28 (1H, t, J 6.8 Hz, H-4’), 7.32 (2H, t, J 7.9 Hz,
7.310 (1H, t, J 8.4 Hz, H-4’). 13C NMR (DMSO) δ (ppm): 14.3
(CH3-Et), 18.3 (CH3-8), 19.3 (CH3-7), 52.2 (CH2), 58.9 (C-4),
59.2 (CH2-Et), 105.2 (C-3), 115.6 (C-6), 116.7 (C-2), 116.8 (C-
9), 118.8 (C-1), 122.3 (C-5a), 126.1 (C-8), 126.5 (C-2’), 127.1
(C-2”), 127.4 (C-4”), 128.4 (C-3”), 128.5 (C-3’), 128.6 (C-4’),
129.9 (C-3a), 133.7 (C-5a), 134.0 (C-7), 137.77 (C-1”), 141.0 (C-
1’), 163.6 (COO). 15N NMR (DMSO) δ (ppm): 61.2 (N-5), 170.4
(N-10). Anal. Calcd. for C29H28N2O2 (436.54): C, 79. 97; H, 6.46;
N, 6.42%. Found: C, 79.84; H, 6.51; N, 6.35%.
H-3’), 7.33 (2H, d, J 8.0 Hz, H-2”), 7.55 (2H, d, J 7.2 Hz, H-2’),
7.72 (1H, s, H-9), 8.43 (1H, d, J 2.0 Hz, H-1). 13C NMR (DMSO)
δ (ppm): 18.4 (CH3-8), 19.6 (CH3-7), 27.0 (CH3-CO), 48.3 (CH2),
84.7 (C-4), 105.4 (C-3), 116.3 (C-9), 116.8 (C-6), 119.1 (C-1),
121.6 (C-9a), 126.2 (C-2), 126.32 (C-2’), 126.36 (C-2”), 126.41
(C-8), 126.45 (C-4”), 127.8 (C-4’), 128.0 (C-3’), 128.3 (C-3”),
133.2 (C-5a), 133.6 (C-7), 134.4 (C-3a), 138.8 (C-1”), 143.8 (C-
1’), 192.5 (CO). 15N NMR (DMSO) δ (ppm): 85.8 (N-5), 170.1
(N-10). Anal. Calcd. for C28H26N2O2 (422.52): C, 79.59; H, 6.20;
N, 6.63%. Found: C, 79.63; H, 6.25; N, 6.56%.
Ethyl
4-(4-methylphenyl)-5-benzyl-7,8-dimethyl-4,5-
dihydropyrrolo[1,2-a]quinoxaline-2-carboxylate (7n). Bright
pink crystals, mp 159-161 ºC (MeOH/Et2O). FT-IR (νmax, cm-1)
1708, 1526, 1509, 1452, 1334, 1227, 1198, 1185, 1138, 1093. 1H
NMR (DMSO) δ (ppm): 1.26 (3H, t, J 7.1 Hz, CH3-Et), 2.07 (3H,
s, CH3-7), 2.16 (3H, s, CH3-8), 2.21 (3H, s, CH3), 4.19 (2H, q, J
Ethyl 4-hydroxy-4-(4-nitrophenyl)-5-benzyl-7,8-dimethyl-4,5-
dihydropyrrolo[1,2-a]quinoxaline-2-carboxylate (6o). Yellow
crystals, mp 176-178 ºC (CHCl3/MeOH). FT-IR (νmax, cm-1)
3345, 1698, 1669, 1623, 1554, 1518, 1451, 1378, 1346, 1263,
1196, 1101. H NMR (DMSO) δ (ppm): 1.25 (3H, t, J 7.1 Hz,
CH3-Et), 2.02 (3H, s, CH3-7), 2.20 (3H, s, CH3-8), 4.17-4.26 (2H,
1
A
7.0 Hz, CH2-Et), 4.25 (1H, d, J 15.9 Hz, CH2 ), 4.58 (1H, d, J
15.8 Hz, CH2 ), 5.63 (1H, s, H-4), 6.24 (1H, d, J 0.9 Hz, H-3),
B
A
m, CH2-Et), 4.15 (1H, d, J 17.4 Hz, CH2 ), 4.53 (1H, d, J 17.4
Hz, CH2 ), 5.99 (1H, d, J 1.4 Hz, H-3), 6.44 (1H, s, H-6), 7.19
6.60 (1H, s, H-6), 6.99 (2H, d, J 8.0 Hz, H-2’), 7.06 (2H, d, J 8.0
Hz, H-3’), 7.23 (1H, t, J 6.6 Hz, H-4”), 7.27-7.32 (4H, m,
aromatic rings), 7.63 (1H, s, H-9), 8.10 (1H, d, J 1.4 Hz, H-1).
The individual chemical shifts, multiplicities and coupling
constants for the 7.27-7.32 ppm multiplet were obtained from
undecoupled HSQC as follows: 7.29 (2H, d, J 7.8 Hz, H-2”),
7.31 (2H, t, J 7.5 Hz, H-3”). 13C NMR (DMSO) δ (ppm): 14.4
(CH3-Et), 18.3 (CH3-8), 19.4 (CH3-7), 20.5 (CH3), 52.1 (CH2),
58.69 (C-4), 59.22 (CH2-Et), 105.17 (C-3), 115.64 (C-6), 116.70
(C-2), 116.72 (C-9), 118.8 (C-1), 122.4 (C-9a), 126.1 (C-8),
126.5 (C-2’), 127.0 (C-4”), 127.1 (C-2”), 128.4 (C-3”), 129.1 (C-
3’), 130.2 (C-3a), 133.7 (C-5a), 134.0 (C-7), 136.7 (C-4’), 137.8
(C-1’), 138.0 (C-1”), 163.7 (COO). 15N NMR (DMSO) δ (ppm):
62.8 (N-5), 169.9 (N-10). Anal. Calcd. for C30H30N2O2 (450.57):
C, 79.97; H, 6.71; N, 6.22%. Found: C, 80.04; H, 6.66; N, 6.18%.
B
(1H, t, J 7.2 Hz, H-4”), 7.27 (2H, t, J 7.3 Hz, H-3”), 7.34 (2H, d,
J 7.5 Hz, H-2”), 7.44 (1H, s, OH), 7.81 (2H, d, J 8.3 Hz, H-2’),
7.82 (1H, s, H-9), 8.20 (2H, d, J 8.9 Hz, H-3’), 8.29 (1H, d, J 1.5
Hz, H-1). 13C NMR (DMSO) δ (ppm): 14.3 (CH3-Et), 18.3 (CH3-
8), 19.5 (CH3-7), 48.3 (CH2), 59.4 (CH2-Et), 84.2 (C-4), 107.2
(C-3), 116.6 (C-9), 116.8 (C-6), 121.2 (C-9a), 123.3 (C-3’),
126.3 (C-2”), 126.5 (C-4”), 126.8 (C-8), 127.6 (C-2’), 128.3 (C-
3”), 132.3 (C-3a), 132.4 (C-5a), 133.8 (C-7), 138.4 (C-1”), 147.0
(C-4’), 150.9 (C-1’), 163.5 (COO). 15N NMR (DMSO) δ (ppm):
84.5 (N-5), 170.4 (N-10) and 369.6 (NO2). Anal. Calcd. for
C29H27N3O4 (481.54): C, 72.33; H, 5.65; N, 8.73%. Found: C,
72.41; H, 5.60; N, 8.65%.
2-Acetyl-4-(3-nitrophenyl)-5-benzyl-4,5-dihydropyrrolo[1,2-
a]quinoxaline (7d). Yellow crystals, mp 99-101 ºC
(MeOH/Et2O). FT-IR (νmax, cm-1) 1643, 1611, 1520, 1504, 1350,
1269, 1230, 1184. 1H NMR (DMSO) δ (ppm): 2.41 (3H, s, CH3),
General procedure for the preparation of pyrrolo[1,2-
a]quinoxalinium bromides 8. To a suspension of 0.5 mmol 4,5-
dihydropyrrolo[1,2-a]quinoxaline 6 or 7 in 15 mL MeOH was
added under stirring 0.15 mL solution of HBr 40% (1 mmol) and
the mixture kept under stirring at room temperature for 30 min.
The solvent was partly evaporated in vacuo and the mixture left
for 20 h. The solid formed was filtered and recrystallized from
MeOH.
A
B
4.48 (1H, d, J 16.0 Hz, CH2 ), 4.48 (1H, d, J 16.4 Hz, CH2 ),
6.11 (1H, s, H-4), 6.49 (1H, s, H-3), 6.86 (1H, d, J 7.6 Hz, H-6),
6.88 (1H, t, J 8.0 Hz, H-8), 7.08 (1H, t, J 7.6 Hz, H-7), 7.23 (1H,
t, J 6.7 Hz, H-4”), 7.29 (2H, d, J 7.8 Hz, H-2”), 7.30 (2H, t, J 7.7
Hz, H-3”), 7.37 (1H, d, J 8.1 Hz, H-3’), 7.58 (1H, d, J 8.0 Hz, H-
2’), 7.86 (1H, d, J 8.0 Hz, H-9), 8.03 (1H, bs, H-6’), 8.08-8.11
(1H, m, H-4’), 8.45 (1H, bs, H-1). 13C NMR (DMSO) δ (ppm):
26.9 (CH3), 52.5 (CH2), 58.4 (C-4), 104.7 (C-3), 114.6 (C-6),
115.7 (C-9), 118.6 (C-8), 120.6 (C-1), 121.1 (C-6’), 122.5 (C-4’),
124.3 (C-9a), 126.5 (C-7), 127.0 (C-2” and C-2), 127.1 (C-4”),
128.5 (C-3”), 129.3 (C-3a), 130.3 (C-3’), 133.0 (C-2’), 135.3 (C-
5a), 137.3 (C-1”), 143.2 (C-1’), 147.8 (C-5’), 192.3 (CO). 15N
NMR (DMSO) δ (ppm): 64.6 (N-5), 168.7 (N-10) and 368.8
(NO2). Anal. Calcd. for C26H21N3O3 (423.46): C, 73.74; H, 5.0;
N, 9.92%. Found: C, 73.83; H, 5.05; N, 9.87%.
Pyrrolo[1,2-a]quinoxalinium bromides 8b,d,g-l,o were
obtained starting from corresponding 4,5-dihydropyrrolo[1,2-
a]quinoxaline 6. Pyrrolo[1,2-a]quinoxalinium bromides 8a and
8m were obtained starting from 4,5-dihydropyrrolo[1,2-
a]quinoxalines 7a and 7m respectively. Pyrrolo[1,2-
a]quinoxalinium bromides 8c and 8e were separated during the
work-up procedures of reaction mixtures performed in the
presence of triethylamine and acetonitrile. After the separation of
the corresponding pyrrolo[1,2-a]quinoxalines 6 and pyrrolo[1,2-
a]benzimidazoles 5, the resultant filtrate was evaporated to
dryness and triturated with acetone. The insoluble part was
filtered off and recrystallized from MeOH to give pyrrolo[1,2-
a]quinoxalinium bromides 8c and 8e respectively.
Ethyl 4-phenyl-5-benzyl-7,8-dimethyl-4,5-dihydropyrrolo[1,2-
a]quinoxaline-2-carboxylate (7m). Pale yellow crystals with mp
164-166 ºC (MeOH/Et2O). FT-IR (νmax, cm-1) 1695, 1609, 1522,
1493, 1452, 1359, 1274, 1240, 1186, 1165, 1099. 1H NMR
(DMSO) δ (ppm): 1.27 (3H, t, J 6.8 Hz, CH3-Et), 2.08 (3H, s,
CH3-7), 2.17 (3H, s, CH3-8), 4.17-4.23 (2H, m, CH2-Et), 4.29
2-Acetyl-4-phenyl-5-benzylpyrrolo[1,2-a]quinoxalinium
bromide (8a). Orange crystals (0.175 g, 77%), mp 200-202 ºC
(MeOH). FT-IR (νmax, cm-1) 3405, 3028, 2965, 1678, 1607, 1549,
1492, 1450, 1390, 1337, 1276, 1262, 1207, 1011. 1H NMR
(CDCl3) δ (ppm): 2.63 (3H, s, CH3), 6.11 (2H, bs, CH2), 7.11
(2H, d, J 6.8 Hz, H-2”), 7.30-7.39 (6H, m, aromatic rings), 7.65
(2H, t, J 7.6 Hz, H-3’), 7.73 (1H, t, J 7.4 Hz, H-4’), 7.85 (1H, d, J
8.4 Hz, H-6), 8.04 (2H, d, J 7.2 Hz, H-2’), 9.02 (1H, d, J 8.4 Hz,
H-9), 10.34 (1H, d, J 1.2 Hz, H-1). The individual chemical
shifts, multiplicities and coupling constants for the 7.30-7.39
multiplet were obtained from undecoupled HSQC as follows:
A
B
(1H, d, J 15.6 Hz, CH2 ), 4.63 (1H, d, J 15.6 Hz, CH2 ), 5.72
(1H, s, H-4), 6.31 (1H, d, J 1.2 Hz, H-3), 6.64 (1H, s, H-6), 7.13
(2H, d, J 6.8 Hz, H-2’), 7.21-7.32 (8H, m, aromatic rings), 7.65
(1H, s, H-9), 8.12 (1H, d, J 1.6 Hz, H-1). The individual
chemical shifts, multiplicities and coupling constants for the
7.21-7.32 ppm multiplet were obtained from undecoupled HSQC
as follows: 7.216 (1H, t, J 7.6 Hz, H-4”), 7.26 (2H, t, J 7.6 Hz,
H-3’), 7.29 (2H, d, J 7.6 Hz, H-2”), 7.309 (2H, t, J 7.9 Hz, H-3”),

ACCEPTED MANUSCRIPT
7.31 (1H, t, J 8.1 Hz, H-4”), 7.330 (1H, t, J 7.9 Hz, H-8), 7.332
for the 7.37-7.38 and 7.88-7.96 ppm multiplet were obtained
from undecoupled HSQC as follows: 7.41 (1H, t, 8.0 Hz, H-4”),
7.42 (2H, t, J 7.0 Hz, H-3”), 7.94 (1H, t, J 7.9 Hz, H-3’), 7.95
(1H, t, J 8.2 Hz, H-8), 7.98 (1H, d, J 8.9 Hz, H-6). 13C NMR
(CDCl3+TFA) δ (ppm): 27.9 (CH3), 56.7 (CH2), 117.2 (C-9),
121.8 (C-6), 122.5 (C-3), 123.4 (C-6’), 125.2 (C-2”), 125.6 (C-
3a), 126.7 (C-1), 127.2 (C-1’ and C-5a), 127.6 (C-4’), 129.0 (C-
9a), 129.3 (C-4”), 129.8 (C-7), 129.9 (C-3”), 131.6 (C-3’), 132.3
(C-8), 132.7 (C-1”), 132.9 (C-2), 134.9 (C-2’), 148.1 (C-5’),
154.4 (C-4), 194.2 (CO). 15N NMR (CDCl3+TFA) δ (ppm): 169.6
(N-5), 179.4 (N-10), 363.6 (NO2). Anal. Calcd. for C26H20BrN3O3
(502.36): C, 62.16; H, 4.01; N, 8.36%. Found: C, 62.22; H, 4.11;
N, 8.25%.
(1H, bs, H-3), 7.34 (2H, t, J 7.5 Hz, H-3”), 7.36 (1H, t, J 8.1 Hz,
H-7). 13C NMR (CDCl3) δ (ppm): 29.1 (CH3), 56.6 (CH2), 118.8
(C-9), 121.4 (C-6), 121.6 (C-3), 125.4 (C-3a), 125.5 (C-2”),
127.1 (C-9a), 127.6 (C-5a), 128.1 (C-7), 128.5 (C-4” and C-1’),
129.0 (C-2’), 129.4 (C-3’), 129.5 (C-3”), 129.6 (C-1), 131.1 (C-
8), 132.5 (C-4’), 132.9 (C-2), 133.7 (C-1”), 157.4 (C-4), 193.4
(CO). 15N NMR (CDCl3) δ (ppm): 169.4 (N-5), 178.2 (N-10).
Anal. Calcd. for C26H21BrN2O (457.36): C, 68.28; H, 4.63; N,
6.12%. Found: C, 68.22; H, 4.71; N, 6.05%.
2-Acetyl-4-(4-chlorophenyl)-5-benzylpyrrolo[1,2-
a]quinoxalinium bromide (8b). Yellow crystals (0.209 g, 85%),
mp 196-198 ºC (MeOH). FT-IR (νmax, cm-1) 3401, 3018, 2974,
1680, 1601, 1548, 1489, 1451, 1390, 1378, 1335, 1272, 1206,
1091, 1012. 1H NMR (CDCl3) δ (ppm): 2.51 (3H, s, CH3), 6.00
(2H, s, CH2), 7.07 (2H, d, J 6.5 Hz, H-2”), 7.29-7.38 (6H, m,
aromatic rings), 7.59 (2H, d, J 8.1 Hz, H-3’), 7.77 (1H, d, J 8.5
Hz, H-6), 8.04 (2H, d, J 7.5 Hz, H-2’), 8.89 (1H, d, J 8.2 Hz, H-
9), 10.14 (1H, s, H-1). The individual chemical shifts,
multiplicities and coupling constants for the signals from 7.29-
7.38 ppm were obtained from undecoupled HSQC as follows:
7.31 (1H, t, J 6.9 Hz, H-8), 7.32 (1H, s, H-3), 7.34 (1H, t, J 7.6
Hz, H-4”), 7.36 (2H, d, J 7.2 Hz, H-3”), 7.38 (1H, t, J 8.0 Hz, H-
7). 13C NMR (CDCl3) δ (ppm): 29.1 (CH3), 56.9 (CH2), 118.8 (C-
9), 121.3 (C-6), 121.4 (C-3), 125.4 (C-2”), 125.5 (C-3a), 126.9
(C-1’), 127.4 (C-5a), 127.6 (C-9a), 128.3 (C-7) 128.7 (C-4”),
129.4 (C-1), 129.6 (C-3”), 129.8 (C-3’), 130.7 (C-2’), 131.2 (C-
8), 133.0 (C-2), 133.6 (C-1”), 139.2 (C-4’), 156.6 (C-4), 193.1
(CO). 15N NMR (CDCl3) δ (ppm): 170.7 (N-5), 179.1 (N-10).
Anal. Calcd. for C26H20BrClN2O (491.81): C, 63.49; H, 4.10; N,
5.70%. Found: C, 63.55; H, 4.14; N, 5.63%.
2-Acetyl-4-(4-nitrophenyl)-5-benzylpyrrolo[1,2-
a]quinoxalinium bromide (8e). Yellow crystals, mp 280-282 ºC
(MeOH). FT-IR (νmax, cm-1) 3405, 3023, 1684, 1602, 1549, 1523,
1492, 1451, 1390, 1351, 1273, 1208, 1134. 1H NMR (DMSO) δ
(ppm): 2.63 (3H, s, CH3), 5.82 (2H, s, CH2), 7.31-7.39 (5H, m,
aromatic rings), 7.62 (1H, d, J 1.3 Hz, H-3), 7.75 (1H, td, J 7.4,
1.2 Hz, H-7), 8.00 (1H, td, J 7.5, 0.8 Hz, H-8), 8.06 (2H, d, J 8.9
Hz, H-2’), 8.07 (1H, d, J 8.7 Hz, H-6), 8.56 (2H, d, J 8.9 Hz, H-
3’), 8.90 (1H, dd, J 8.5, 1.2 Hz, H-9), 9.88 (1H, d, J 1.3 Hz, H-1).
The individual chemical shifts, multiplicities and coupling
constants for the signals from 7.31-7.39 ppm were obtained from
undecoupled HSQC as follows: 7.32 (1H, t, J 6.8 Hz, H-4”), 7.34
(2H, t, J 7.5 Hz, H-3”), 7.38 (2H, d, J 7.6 Hz, H-2”). 13C NMR
(DMSO) δ (ppm): 27.9 (CH3), 55.1 (CH2), 117.4 (C-9), 121.6 (C-
3), 121.8 (C-6), 124.5 (C-3’), 125.9 (C-3a), 126.0 (C-2”), 126.7
(C-1), 126.9 (C-9a), 127.6 (C-5a), 128.1 (C-4”), 128.7 (C-7),
128.8 (C-3”), 130.3 (C-2’), 131.3 (C-8), 132.3 (C-2), 133.8 (C-
1”), 134.1 (C-1’), 149.7 (C-4’), 155.3 (C-4), 193.0 (CO). 15N
NMR (DMSO) δ (ppm): 170.0 (N-5), 180.0 (N-10), 367.7 (NO2).
Anal. Calcd. for C26H20BrN3O3 (502.36): C, 62.16; H, 4.01; N,
8.36%. Found: C, 62.11; H, 3.95; N, 8.41%.
2-Acetyl-4-(4-methoxyphenyl)-5-benzylpyrrolo[1,2-
a]quinoxalinium bromide (8c). Light yellow crystals, mp 187-
189 ºC (MeOH). FT-IR (νmax, cm-1) 3417, 3019, 1680, 1605,
1545, 1488, 1451, 1389, 1336, 1262, 1207, 1180. 1H NMR
(CDCl3) δ (ppm): 2.62 (3H, s, CH3), 3.91 (3H, s, OCH3), 6.12
(2H, s, CH2), 7.09-7.12 (4H, m, aromatic rings), 7.32-7.36 (5H,
m, aromatic rings), 7.38 (1H, s, H-3), 7.80 (1H, d, J 9.5 Hz, H-6),
7.93 (2H, d, J 7.8 Hz, H-2’), 8.96 (1H, d, J 9.2 Hz, H-9), 10.23
(1H, s, H-1). The individual chemical shifts, multiplicities and
coupling constants for the signals from 7.09-7.12 and 7.32-7.36
ppm were obtained from undecoupled HSQC as follows: 7.107
(2H, d, J 8.4 Hz, H-3’), 7.108 (2H, d, J 7.0 Hz, H-2”), 7.31 (1H,
t, J 7.6 Hz, H-4”), 7.32 (1H, t, J 7.5 Hz, H-8), 7.33 (1H, t, J 8.2
Hz, H-7), 7.34 (2H, t, J 7.7 Hz, H-3”). 13C NMR (CDCl3) δ
(ppm): 29.2 (CH3), 55.7 (OCH3), 56.7 (CH2), 114.9 (C-3’), 118.8
(C-9), 120.4 (C-1’), 121.5 (C-6), 121.8 (C-3), 125.5 (C-2”),
125.6 (C-3a), 127.3 (C-5a), 127.5 (C-9a), 128.1 (C-7) 128.5 (C-
4”), 129.2 (C-1), 129.5 (C-3”), 130.9 (C-8), 131.2 (C-2’), 132.8
(C-2), 134.0 (C-1”), 157.7 (C-4), 163.0 (C-4’), 193.4 (CO). 15N
NMR (CDCl3) δ (ppm): 169.1 (N-5), 178.5 (N-10). Anal. Calcd.
for C27H23BrN2O2 (487.46): C, 66.53; H, 4.75; N, 5.75%. Found:
C, 66.47; H, 4.71; N, 5.82%.
2-Carbethoxy-4-(4-fluorophenyl)-5-benzylpyrrolo[1,2-
a]quinoxalinium bromide (8g). Yellow crystals (0.215 g, 85%),
mp 193-195 ºC (MeOH/Et2O). FT-IR (νmax, cm-1) 3385, 3029,
1719, 1601, 1549, 1490, 1452, 1393, 1368, 1335, 1273, 1201,
1133. 1H NMR (CDCl3) δ (ppm): 1.40 (3H, t, J 7.2 Hz, CH3-Et),
4.38 (2H, q, J 7.2 Hz, CH2-Et), 6.13 (2H, bs, CH2), 7.12 (2H, d, J
8.0 Hz, H-2”), 7.28-7.36 (5H, m, aromatic rings), 7.40 (1H, d, J
1.2 Hz, H-3), 7.55 (1H, td, J 8.6, 1.2 Hz, H-7), 7.67 (1H, td, J
8.3. 1.0 Hz, H-8), 7.97 (1H, dd, J 8.8, 0.8 Hz, H-6), 8.06 (2H, dd,
J 7.2, 4.8 Hz, H-2’), 8.46 (1H, dd, J 8.4, 1.2 Hz, H-9), 9.16 (1H,
d, J 1.2 Hz, H-9). The individual chemical shifts, multiplicities
and coupling constants for the 7.28-7.36 ppm multiplet were
obtained from undecoupled HSQC as follows: 7.31 (2H, t, J 8.2
Hz, H-3’), 7.32 (1H, t, J 7.0 Hz, H-4”), 7.35 (2H, t, J 7.6 Hz, H-
3”). 13C NMR (CDCl3) δ (ppm): 14.3 (CH3-Et), 57.0 (CH2), 61.5
(CH2-Et), 116.8 (d, JC-F 22.1 Hz, C-3’), 117.6 (C-9), 122.1 (C-6),
122.9 (C-3), 124.4 (d, JC-F 3.0 Hz, C-1’), 125.4 (C-2” and C-2),
125.6 (-3a), 126.7 (C-1), 127.0 (C-9a), 127.3 (C-5a), 128.5 (C-
4”), 128.7 (C-7), 129.5 (C-3”), 131.4 (C-8), 131.8 (d, JC-F 9.1 Hz,
C-2’), 133.8 (C-1”), 156.1 (C-4), 161.7 (COO), 164.9 (d, JC-F
255.5 Hz, C-4’). 15N NMR (CDCl3) δ (ppm): 171.9 (N-5), 178.2
(N-10). 19F NMR (CDCl3) δ (ppm): -104.8. Anal. Calcd. for
C27H22BrFN2O2 (505.38): C, 64.17; H, 4.39; N, 5.54%. Found: C,
64.11; H, 4.31; N, 5.62%. Single crystal X-ray: C27H23FN2O3, Mr
= 442.47 g mol-1, size 0.400.200.05 mm3, tmonoclinic, space
group P21/c=, a 17.2774(7) Å, b = 7.0755(3) Å, c = 19.4030(7)
Å,  = 114.059(5), V = 2165.90(15) Å3, Z = 4, ρcalcd = 1.357 g
cm-3, μ(MoKα) = 0.095 mm-1, F(000) = 928, 8024 reflections in
h(-14/20), k(-8/8), l(-22/22), measured in the range 4.26  Θ 
48.8, T = 200 K, completeness Θmax = 99.94%, 3541 independent
2-Acetyl-4-(3-nitrophenyl)-5-benzylpyrrolo[1,2-
a]quinoxalinium bromide (8d). Yellow crystals (0.220 g, 88%),
mp 223-225 ºC (MeOH). FT-IR (νmax, cm-1) 3379, 3003, 1683,
1612, 1535, 1492, 1450, 1392, 1350, 1275, 1207, 1134. 1H NMR
(CDCl3+TFA) δ (ppm): 2.65 (3H, s, CH3), 5.75 (1H, d, J 17.2
A
B
Hz, CH2 ), 5.92 (1H, d, J 17.2 Hz, CH2 ), 7.07-7.08 (2H, m, H-
2”), 7.37-7.38 (3H, m, aromatic rings), 7.44 (1H, bs, H-3), 7.69
(1H, t, J 8.0 Hz, H-7), 7.88-7.96 (3H, m, aromatic rings), 8.25
(1H, d, J 7.2 Hz, H-2’), 8.42 (1H, d, J 8.4 Hz, H-9), 8.45 (1H, bs,
H-6’), 8.56 (1H, d, J 8.0 Hz, H-4’), 9.28 (1H, bs, H-9). The
individual chemical shifts, multiplicities and coupling constants
reflections, Rint = 0.0284, 300 parameters, 0 restraints, R1obs
=

14
Tetrahedron
ACCEPTED MANUSCRIPT
0.0446, wR2obs = 0.0937, R1all = 0.0674, wR2all = 0.1037, GoF =
179.9 (N-10), 365.2 (NO2). Anal. Calcd. for C23H22BrN3O3
(468.34): C, 58.98; H, 4.73; N, 8.97%. Found: C, 59.06; H, 4.81;
N, 8.91%.
1.051, largest difference peak and hole: 0.15/-0.23 e A-3. These
data
www.ccdc.cam.ac.uk/conts/retrieving.html
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK). CCDC: 1431563.
can
be
obtained
free
of
(or
charge
from
via
the
2-Carbethoxy-4-(4-chlorophenyl)-5-ethyl-7,8-
dimethylpyrrolo[1,2-a]quinoxalinium bromide (8k). Yellow
crystals (0.190 g, 78%), mp 240-242 ºC (MeOH). FT-IR (νmax
,
2-Carbethoxy-4-(4-chlorophenyl)-5-benzylpyrrolo[1,2-
cm-1) 3420, 2981, 1716, 1601, 1545, 1501, 1454, 1420, 1392,
1375, 1348, 1277, 1214, 1087. 1H NMR (CDCl3+TFA) δ (ppm):
1.39 (3H, t, J 6.8 Hz, CH3-2), 1.54 (3H, t, J 6.8 Hz, CH3-Et), 2.54
(3H, s, CH3-7), 2.56 (3H, s, CH3-8), 4.40 (2H, q, J 7.2 Hz, CH2-
2), 4.70 (2H, q, J 7.2 Hz, CH2-Et), 7.28 (1H, s, H-3), 7.71 (4H, d,
J 8.8 Hz, H-2’ and H-3’), 7.92 (1H, s, CH-6), 8.03 (1H, s, H-9),
8.92 (1H, s, H-1). 13C NMR (CDCl3+TFA) δ (ppm): 14.2 (CH3-
2), 15.0 (CH3-Et), 20.3 (CH3-7 and CH3-8), 48.2 (CH2-Et), 62.1
(CH2-2), 116.9 (C-9), 120.9 (C-6), 121.7 (C-3), 124.3 (C-5a),
124.6 (C-1), 125.3 (C-9a and C-2), 125.5 (C-3a), 126.5 (C-1’),
129.9 (C-3’), 130.3 (C-2’), 132.4 (C-2), 139.3 (C-1’), 140.0 (C-
7), 143.0 (C-8), 153.4 (C-4), 162.4 (COO). 15N NMR
(CDCl3+TFA) δ (ppm): 176.9 (N-5), 178.6 (N-10). Anal. Calcd.
for C24H24BrClN2O2 (487.82): C, 59.09; H, 4.96; N, 5.74%.
Found: C, 59.13; H, 4.89; N, 5.79%.
a]quinoxalinium bromide (8h). Yellow crystals (0.201 g, 77%),
mp 196-197 ºC (MeOH). FT-IR (νmax, cm-1) 3366, 3023, 2997,
2978, 1716, 1603, 1553, 1489, 1451, 1397, 1336, 1276, 1218,
1134. 1H NMR (CDCl3) δ (ppm): 1.45 (3H, t, J 7.2 Hz, CH3-Et),
4.38 (2H, q, J 7.2 Hz, CH2-Et), 6.18 (2H, bs, CH2), 7.09 (2H, dd,
J 6.0, 1.9 Hz, H-2”), 7.31-7.34 (3H, m, aromatic rings), 7.36 (1H,
d, J 1.1 Hz, H-3), 7.51 (1H, t, J 7.7 Hz, H-7), 7.59 (2H, d, J 8.6
Hz, H-3’), 7.61 (1H, t, J 7.6 Hz, H-8), 7.98 (1H, d, J 8.5 Hz, H-
6), 8.03 (2H, d, J 7.8 Hz, H-2’), 8.50 (1H, d, J 7.8 Hz, H-9), 9.22
(1H, d, J 1.1 Hz, H-9). The individual chemical shifts,
multiplicities and coupling constants for the 7.31-7.34 ppm
multiplet were obtained from undecoupled HSQC as follows:
7.31 (1H, t, J 7.8 Hz, H-4”), 7.33 (2H, t, J 7.7 Hz, H-3”). 13C
NMR (CDCl3) δ (ppm): 14.4 (CH3-Et), 57.2 (CH2), 61.7 (CH2-
Et), 117.2 (C-9), 122.5 (C-6), 122.9 (C-3), 125.4 (C-2), 125.5 (C-
2”), 125.8 (C-3a), 126.4 (C-1), 126.8 (C-1’), 127.1 (C-9a), 127.4
(C-5a), 128.6 (C-4”), 128.9 (C-7), 129.5 (C-3”), 129.8 (C-3’),
130.8 (C-2’), 131.3 (C-8), 134.0 (C-1”), 139.2 (C-4’), 156.2 (C-
4), 161.7 (COO). 15N NMR (CDCl3) δ (ppm): 170.8 (N-5), 178.1
(N-10). Anal. Calcd. for C27H22BrClN2O2 (521.83): C, 62.14; H,
4.25; N, 5.37%. Found: C, 62.26; H, 4.29; N, 5.24%.
2-Acetyl-4-phenyl-5-benzyl-7,8-dimethylpyrrolo[1,2-
a]quinoxalinium bromide (8l). Yellow crystals (0.199 g, 82%),
mp 226-228 ºC (MeOH). FT-IR (νmax, cm-1) 3417, 3031, 2996,
1677, 1601, 1543, 1499, 1450, 1376, 1350, 1277, 1197. 1H NMR
(CDCl3+TFA) δ (ppm): 2.35 (3H, s, CH3-7), 2.52 (3H, s, CH3-8),
2.73 (3H, s, CH3), 5.82 (2H, s, CH2), 7.06-7.08 (2H, m, H-2”),
7.36-7.38 (3H, m, aromatic rings), 7.43 (1H, d, J 1.0 Hz, H-3),
7.61-7.63 (4H, m, aromatic ring), 7.73-7.77 (1H, m, H-4’), 8.17
(1H, s, H-9), 9.22 (1H, d, J 1.0 Hz, H-1). The individual
chemical shifts, multiplicities and coupling constants for the
7.36-7.38 and 7.61-7.63 ppm multiplets were obtained from
undecoupled HSQC as follows: 7.37 (1H, t, J 7.6 Hz, H-4”), 7.38
(2H, t, J 7.1 Hz, H-3”), 7.62 (2H, d, J 7.9 Hz, H-2’), 7.63 (2H, t,
J 7.8 Hz, H-3’). 13C NMR (CDCl3+TFA) δ (ppm): 20.1 (CH3-8),
20.2 (CH3-7), 27.7 (CH3), 56.0 (CH2), 117.2 (C-9), 121.7 (C-6),
122.4 (C-3), 125.11 (C-5a), 125.13 (C-9a), 125.32 (C-2”), 125.4
(C-1), 125.7 (C-3a), 127.7 (C-1’), 128.4(C-2’), 129.0 (C-4”),
129.7 (C-3”), 129.8 (C-3’), 131.7 (C-2), 133.1 (C-1”), 133.2 (C-
4’), 140.2 (C-7), 143.4 (C-8), 156.2 (C-4), 197.1 (CO). 15N NMR
(CDCl3+TFA) δ (ppm): 169.8 (N-5), 179.7 (N-10). Anal. Calcd.
for C28H25BrN2O (485.41): C, 69.28; H, 5.19; N, 5.77%. Found:
C, 69.23; H, 5.23; N, 5.64%.
2-Carbethoxy-4-(4-nitrophenyl)-5-benzylpyrrolo[1,2-
a]quinoxalinium bromide (8i). Yellow crystals (0.211 g, 79%),
mp 236-238 ºC (MeOH). FT-IR (νmax, cm-1) 3426, 2997, 2877,
1707, 1608, 1555, 1525, 1493, 1457, 1349, 1279, 1205. 1H NMR
(DMSO) δ (ppm): 1.34 (3H, t, J 6.8 Hz, CH3), 4.37 (2H, q, J 7.2
Hz, CH2-Et), 5.85 (2H, s, CH2), 7.32-7.40 (5H, m, aromatic
rings), 7.45 (1H, d, J 1.2 Hz, H-3), 7.76 (1H, td, J 7.5, 1.0 Hz, H-
7), 8.00 (1H, t, J 8.0 Hz, H-8), 8.08 (2H, d, J 8.8 Hz, H-2’), 8.09
(1H, d, J 8.7 Hz, H-6), 8.55 (2H, d, J 8.8 Hz, H-3’), 8.97 (1H, dd,
J 7.6, 0.9 Hz, H-9), 9.87 (1H, d, J 1.2 Hz, H-1). The individual
chemical shifts, multiplicities and coupling constants for the
signals from 7.31-7.39 ppm were obtained from undecoupled
HSQC as follows: 7.32 (1H, t, J 7.4 Hz, H-4”), 7.34 (2H, t, J 7.7
Hz, H-3”), 7.38 (2H, d, J 7.6 Hz, H-2”). 13C NMR (DMSO) δ
(ppm): 14.2 (CH3), 55.2 (CH2), 61.1 (CH2-Et), 117.6 (C-9), 121.9
(C-6), 122.0 (C-3), 124.5 (C-2), 124.6 (C-3’), 125.9 (C-3a),
126.1 (C-2”), 126.8 (C-5a), 127.2 (C-1), 127.6 (C-9a), 128.1 (C-
4”), 128.8 (C-7), 128.9 (C-3”), 130.3 (C-2’), 131.4 (C-8), 133.9
(C-1”), 134.1 (C-1’), 149.7 (C-4’), 155.1 (C-4), 161.8 (COO).
15N NMR (DMSO) δ (ppm): 170.3 (N-5), 180.2 (N-10), 367.5
(NO2). Anal. Calcd. for C27H22BrN3O4 (532.38): C, 60.91; H,
4.16; N, 7.89%. Found: C, 60.85; H, 4.11; N, 7.94%.
2-Carbethoxy-4-phenyl-5-benzyl-7,8-dimethylpyrrolo[1,2-
a]quinoxalinium bromide (8m). Yellow crystals (0.185 g, 72%),
mp 197-198 ºC (MeOH). FT-IR (νmax, cm-1) 3392, 2979, 1714,
1602, 1545, 1496, 1451, 1374, 1350, 1284, 1203, 1111, 1022. 1H
NMR (CDCl3) δ (ppm): 1.40 (3H, t, J 7.1 Hz, CH3-Et), 2.30 (3H,
s, CH3-7), 2.39 (3H, s, CH3-8), 4.37 (2H, q, J 7.1 Hz, CH2-Et),
6.19 (2H, s, CH2), 7.09 (2H, d, J 6.2 Hz, H-2”), 7.29-7.32 (4H,
m, aromatic rings), 7.59 (2H, t, J 7.7 Hz, H-3’), 7.67 (1H, t, J 7.4
Hz, H-4’), 7.84 (1H, s, H-6), 7.92 (2H, d, J 6.7 Hz, H-2’), 8.30
(1H, s, H-9), 9.13 (1H, s, H-1). The individual chemical shifts,
multiplicities and coupling constants for the 7.29-7.32 ppm
multiplet were obtained from undecoupled HSQC as follows:
7.32 (1H, t, J 7.6 Hz, H-4”), 7.33 (1H, s, H-3), 7.35 (2H, t, J 7.6
Hz, H-3”). 13C NMR (CDCl3) δ (ppm): 14.4 (CH3-Et), 20.1 (CH3-
8), 20.2 (CH3-7), 56.6 (CH2), 61.5 (CH2-Et), 117.0 (C-9), 122.2
(C-3), 122.5 (C-6), 125.2 (C-5a and C-3a), 125.1 (C-9a), 125.4
(C-1), 125.7 (C-2”), 128.3 (C-4”), 128.5 (C-1’), 129.1 (C-2’),
129.3 (C-3”), 129.4 (C-3’), 132.4 (C-4’), 134.2 (C-1”), 139.0 (C-
7), 142.3 (C-8), 155.5 (C-4), 162.1 (COO). 15N NMR (CDCl3) δ
(ppm): 171.5 (N-5), 178.9 (N-10). Anal. Calcd. for C29H27BrN2O2
2-Acetyl-4-(4-nitrophenyl)-5-ethyl-7,8-dimethylpyrrolo[1,2-
a]quinoxalinium bromide (8j). Yellow crystals (0.199 g, 85%),
mp 261-263 ºC (MeOH). FT-IR (νmax, cm-1) 3400, 3111, 2985,
1
1679, 1595, 1521, 1502, 1367, 1348, 1282, 1198. H NMR
(CDCl3+TFA) δ (ppm): 1.57 (3H, t, J 6.8 Hz, CH3-Et), 2.55 (3H,
s, CH3-7), 2.58 (3H, s, CH3-8), 2.63 (3H, s, CH3), 4.63 (2H, q, J
7.2 Hz, CH2-Et), 7.23 (1H, s, H-3), 7.86 (1H, s, CH-6), 8.06 (2H,
d, J 8.0 Hz, H-2’), 8.13 (1H, s, H-9), 8.60 (2H, d, J 8.4 Hz, H-3’),
9.09 (1H, s, H-1). 13C NMR (CDCl3+TFA) δ (ppm): 15.0 (CH3-
Et), 20.3 (CH3-8), 20.4 (CH3-7), 27.9 (CH3), 48.4 (CH2-Et), 117.4
(C-9), 120.5 (C-6), 120.7 (C-3), 124.2 (C-5a), 124.9 (C-1), 125.1
(C-3’), 125.2 (C-3a), 125.5 (C-9a), 130.3 (C-2’), 132.4 (C-2),
133.7 (C-1’), 140.4 (C-7), 143.7 (C-8), 150.2 (C-4’), 152.2 (C-4),
194.1 (CO-CH3). 15N NMR (CDCl3+TFA) δ (ppm): 174.4 (N-5),

ACCEPTED MANUSCRIPT
(515.44): C, 67.57; H, 5.28; N, 5.43%. Found: C, 67.62; H, 5.32;
N, 5.37%.
H-4”), 7.25 (2H, t, 7.2 Hz, H-3”), 7.30 (2H, d, 7.2 Hz, H-2”),
7.40 (2H, d, J 8.4 Hz, H-3’), 7.60 (2H, d, J 8.4 Hz, H-2’), 7.95
(1H, d, J 7.6 Hz, H-9), 7.98 (1H, d, J 1.2 Hz, H-1). 13C NMR
(CDCl3) δ (ppm): 14.4 (CH3-Et), 48.6 (CH2), 51.7 (CH3), 60.1
(CH2-Et), 89.7 (C-4), 110.0 (C-3), 114.6 (C-9), 115.0 (C-6),
117.4 (C-1), 118.4 (C-2), 118.9 (C-8), 123.0 (C-9a), 126.1 (C-
2”), 126.4 (C-7), 126.6 (C-4”), 127.91 (C-3’), 128.24 (C-3”),
128.7 (C-2’), 128.9 (C-3a), 134.0 (C-4’), 135.9 (C-5a), 137.3 (C-
1”), 141.5 (C-1’), 164.4 (COO). 15N NMR (CDCl3) δ (ppm): 81.4
(N-5), 170.9 (N-10). Anal. Calcd. for C28H25ClN2O3 (472.96): C,
71.10; H, 5.33; N, 5.92%. Found: C, 71.16; H, 5.29; N, 5.85%.
2-Carbethoxy-4-(4-nitrophenyl)-5-benzyl-7,8-
dimethylpyrrolo[1,2-a]quinoxalinium bromide (8o). Yellow
crystals (0.229 g, 82%), mp 208-210 ºC (MeOH). FT-IR (νmax
,
cm-1) 3323, 3024, 2977, 1712, 1668, 1596, 1525, 1499, 1452,
1
1349, 1284, 1208, 1135. H NMR (CDCl3+TFA) δ (ppm): 1.39
(3H, t, J 7.20 Hz, CH3-Et), 2.36 (3H, s, CH3-7), 2.53 (3H, s, CH3-
8), 4.41 (2H, q, J 7.20 Hz, CH2-Et), 5.85 (2H, s, CH2), 7.04 (2H,
bs, H-2”), 7.35-7.38 (4H, m, aromatic rings), 7.71 (1H, s, H-6),
7.93 (2H, d, J 8.0 Hz, H-2’), 8.05 (1H, s, H-9), 8.43 (2H, d, J 8.0
Hz, H-3’), 9.04 (1H, s, H-1). The individual chemical shifts,
multiplicities and coupling constants for the 7.35-7.38 ppm
multiplet were obtained from undecoupled HSQC as follows:
7.35 (1H, t, J 7.9 Hz, H-4”), 7.356 (1H, s, H-3), 7.363 (2H, bs,
H-3”). 13C NMR (CDCl3+TFA) δ (ppm): 14.1 (CH3-Et), 20.2
(CH3-7), 20.3 (CH3-8), 56.3 (CH2), 116.7 (C-9), 121.7 (C-6),
122.3 (C-3), 124.6 (C-3’), 125.0 (C-2), 125.1 (C-9a and C-5a),
125.2 (C-2”), 125.6 (C-1), 125.9 (C-3a), 129.1 (C-4”), 129.8 (C-
3”), 130.4 (C-2’), 133.1 (C-1”), 133.60 (C-1’), 140.2 (C-7), 143.5
(C-8), 150.2 (C-4’), 153.0 (C-4), 162.4 (COO). 15N NMR
(CDCl3+TFA) δ (ppm): 169.3 (N-5), 178.3 (N-10), 363.7 (NO2).
Anal. Calcd. for C29H26BrN3O4 (560.44): C, 62.15; H, 4.67; N,
7.50%. Found: C, 62.22; H, 4.71; N, 7.44%.
2-Acetyl-4-methoxy-4-phenyl-5-benzyl-7,8-dimethyl-4,5-
dihydropyrrolo[1,2-a]quinoxaline (9l). Pale brown crystals, mp
149-151 ºC (MeOH). FT-IR (νm1ax, cm-1) 3125, 2916, 1662, 1521,
1494, 1446, 1332, 1254, 1185. H NMR (DMSO) δ (ppm): 2.02
(3H, s, CH3-7), 2.22 (3H, s, CH3-8), 2.40 (3H, s, CH3-CO), 2.98
A
(3H, s, CH3-O), 4.40 (1H, d, J 17.6 Hz, CH2 ), 4.48 (1H, d, J
B
17.6 Hz, CH2 ), 5.92 (1H, d, J 1.6 Hz, H-3), 6.47 (1H, s, H-6),
7.14 (1H, t, J 5.2 Hz, H-4”), 7.16 (2H, d, J 6.9 Hz, H-2”), 7.21
(2H, t, J 7.2 Hz, H-3”), 7.27 (1H, t, J 7.0 Hz, H-4’), 7.30 (2H, t, J
6.6 Hz, H-3’), 7.55 (2H, d, J 6.8 Hz, H-2’), 7.81 (1H, s, H-9),
8.55 (1H, d, J 1.6 Hz, H-1). 13C NMR (DMSO) δ (ppm): 18.3
(CH3-8), 19.5 (CH3-7), 27.0 (CH3-CO), 47.8 (CH2), 51.2 (CH3-
O), 89.7 (C-4), 107.3 (C-3), 115.7 (C-6), 116.3 (C-9), 119.0 (C-
1), 120.6 (C-9a), 126.0 (C-2”), 126.3 (C-4”), 126.5 (C-2), 126.6
(C-8), 126.9 (C-2’), 127.8 (C-3’), 128.0 (C-4’), 128.1 (C-3”),
129.7 (C-3a), 133.3 (C-5a), 133.9 (C-7), 137.7 (C-1”), 142.6 (C-
1’), 192.4 (CO). 15N NMR (DMSO) δ (ppm): 78.4 (N-5), 172.8
(N-10). Anal. Calcd. for C29H28N2O2 (436.54): C, 79.79; H, 6.46;
N, 6.42%. Found: C, 79.85; H, 6.40; N, 6.35%.
General procedure for preparation of 4-methoxy-3,4-
dihydropyrrolo[1,2-a]quinoxalines 9.
A suspension of a
pyrrolo[1,2-a]quinoxalinium bromide 8 (0.4 mmol) in 15 mL
MeOH was treated under stirring with 0.2 mL solution of
CH3ONa 25% in MeOH (0.85 mmol) and the mixture was kept
under stirring at room temperature for 20 min. The solvent was
partly evaporated in vacuo, the solid formed filtered, washed on
filter with water and recrystallized from MeOH.
Ethyl 4-phenylpyrrolo[1,2-a]quinoxaline-2-carboxylate (10).
Yellow crystals with mp 204-206 ºC (acetone). FT-IR (νmax, cm-1)
3133, 1706, 1585, 1538, 1481, 1352, 1263, 1192, 1167, 1027. 1H
NMR (DMSO) δ (ppm): 1.35 (3H, t, J 6.8 Hz, CH3), 4.34 (2H, q,
J 7.2 Hz, CH2), 7.25 (1H, d, J 1.2 Hz, H-3), 7.58-7.68 (5H, m,
aromatic rings), 7.97-8.00 (3H, m, aromatic rings), 8.53 (1H, d, J
8.0 Hz, H-9), 9.12 (1H, d, J 1.3 Hz, H-1). The individual
chemical shifts, multiplicities and coupling constants for the
signals from 7.58-8.00 ppm were obtained from undecoupled
HSQC as follows: 7.60 (1H, t, J 8.3 Hz, H-7), 7.62 (2H, t, J 9.0
Hz, H-3’), 7.62 (1H, t, J 7.5 Hz, H-8), 7.65 (1H, t, J 8.0 Hz, H-
Ethyl 4-methoxy-4-phenyl-5-benzyl-4,5-dihydropyrrolo[1,2-
a]quinoxaline-2-carboxylate (9f). Yellow crystals, mp 140-142
ºC (MeOH). FT-IR (νmax, cm-1) 1708, 1613, 1555, 1522, 1493,
1453, 1335, 1249, 1194, 1095. 1H NMR (DMSO) δ (ppm): 1.33
(3H, t, J 6.80 Hz, CH3-Et), 3.08 (3H, s, OCH3), 4.23-4.32 (2H, m,
A
CH2B-Et), 4.44 (1H, d, J 17.5 Hz, CH2 ), 4.56 (1H, d, J 17.5 Hz,
CH2 ), 6.20 (1H, d, J 1.5 Hz, H-3), 6.68 (1H, d, J 8.1 Hz, H-6),
6.89 (1H, t, J 7.5 Hz, H-8), 7.00 (1H, t, J 7.2 Hz, H-7), 7.13-7.28
(8H, m, aromatic rings), 7.54 (1H, d, J 7.8 Hz, H-9), 7.60 (2H, d,
J 6.6 Hz, H-2’), 7.97 (1H, d, J 1.5 Hz, H-1). The individual
chemical shifts, multiplicities and coupling constants for the
7.13-7.28 ppm multiplet were obtained from undecoupled HSQC
as follows: 7.17 (2H, d, J 7.8 Hz, H-2”), 7.18 (1H, t, J 7.7 Hz, H-
4”), 7.24 (2H, t, J 7.5 Hz, H-3”), 7.26 (1H, t, J 7.6 Hz, H-4’),
7.29 (2H, t, J 7.7 Hz, H-3’). 13C NMR (DMSO) δ (ppm): 14.4
(CH3-Et), 48.7 (CH2), 51.8 (OCH3), 60.1 (CH2-Et), 90.2 (C-4),
109.9 (C-3), 114.6 (C-9), 115.0 (C-6), 117.3 (C-1), 118.2 (C-2),
119.0 (C-8), 123.1 (C-9a), 126.1 (C-2”), 126.3 (C-7), 126.5 (C-
4”), 127.2 (C-2’), 127.9 (C-3’), 128.1 (C-4’), 128.3 (C-3”), 129.4
(C-3a), 136.1 (C-5a), 137.6 (C-1”), 142.7 (C-1’), 164.5 (COO).
15N NMR (DMSO) δ (ppm): 81.9 (N-5), 171.1 (N-10). Anal.
Calcd. for C28H26N2O3 (438.52): C, 76.69; H, 5.98; N, 6.39%.
Found: C, 76.74; H, 6.05; N, 6.31%.
4’), 7.97 (1H, d, J 8.3 Hz, H-6), 7.98 (2H, d, J 8.0 Hz, H-2’). 13
C
NMR (DMSO) δ (ppm): 14.3 (CH3), 60.2 (CH2), 108.6 (C-3),
115.5 (C-9), 119.6 (C-2), 118.0 (C-1), 124.6 (C-3a), 126.2 (C-
9a), 126.8 (C-7), 128.4 (C-2’), 128.5 (C-4’), 128.7 (C-3’), 129.7
(C-6), 130.3 (C-8), 135.8 (C-5a), 137.1 (C-1’), 153.8 (C-4),
163.4 (COO). 15N NMR (DMSO) δ (ppm): 284.5 (N-5), 180.2
(N-10). Anal. Calcd. for C20H16N2O2 (316.35): C, 75.93; H, 5.10;
N, 8.85%. Found: C, 75.86; H, 5.06; N, 8.91%.
Acknowledgements
This work was supported by the following grants of the
Romanian National Authority for Scientific Research, CNCS –
UEFISCDI: Project PN-II-ID-PCCE-2011-2-0028, Contract
4/2012 and Project “GreenTech” PN-II-PT-PCCA-2013-4-0842,
Contract 105/2014. This paper is dedicated to the 150th
anniversary of the Romanian Academy.
Ethyl
4-methoxy-4-(4-chlorophenyl)-5-benzyl-4,5-
(9h). Pale
dihydropyrrolo[1,2-a]quinoxaline-2-carboxylate
References and notes
brown crystals, mp 155-157 ºC (MeOH/acetone). FT-IR (νmax
,
cm-1) 3053, 2976, 2947, 1709, 1609, 1557, 1525, 1493, 1337,
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