Enamine rearrangement of pyridinium salts to indole ring: A combined experimental and molecular modeling study

Article abstract of DOI:10.1002/jhet.1629

N-Alkyl pyridinium (II) and N-alkyl isoquinolinium salts V undergo cyclization reaction when heated with sodium bicarbonate to give the corresponding indolizine derivatives III and VI, respectively, which undergo ring opening and recyclization reactions when heated with aqueous sodium hydroxide to give the corresponding indole derivatives IV and IX, respectively. Molecular modeling tools including Molecular Mechanics using Augmented MM3 parameters followed by geometry optimization calculations in MO-G using PM3 parameters were performed to gain better understanding and more insights on the thermodynamic properties of the recyclization reactions of compounds IIa-g to the corresponding IIIa-g and IIIa-g to the corresponding IVa-g. The results were in excellent agreement with the experimental data and hence were proven to be a good tool in explaining different yields % because of the steric and electronic effects of electron-withdrawing groups on the reactivity of the pyridine ring for nucleophilic attack.

Full text of DOI:10.1002/jhet.1629

638
Enamine Rearrangement of Pyridinium Salts to Indole Ring: A Combined
Experimental and Molecular Modeling Study
Vol 50
a
b
*
Aisha Hosaan and Ahmed A. Fadda
aFaculty of Education of Girls, King Khaled University, Abha, Saudi Arabia
bChemistry Department, Faculty of Science, Mansoura University, El-Gomhoria Street, Mansoura 35516, Egypt
*
E-mail: afadda2@yahoo.com
Received November 29, 2011
DOI 10.1002/jhet.1629
Published online in Wiley Online Library (wileyonlinelibrary.com).
R
X
R'
R
N
N
R'
NH
N
R
H
R'
IIIa, R= 6-NO2, R'= CH3 IVa, R'= 3-CH3, X= 5-NO2
, R= 6-NO2, R'= C6H5
, R'= 3-C6H5, X= 5-NO2
, R= 8-NO2, R'= CH3
, R'= 3-CH3, X= 7-NO2
, R= 8-NO2, R'= C6H5
, R'= 3-C6H5, X= 7-NO2
, R= 6-NO2, R'= C(CH3)3
, R'= 3-C(CH3)3, X= 5-NO2
, R= 5-F, R'= CH3
, R'= 3-CH3, X= 4-F
, R= 5-F, R'= C6H5
, R'= 3-C6H5, X= 4-F
R'
b
c
d
e
f
g
b
c
d
e
f
g
IXa, R= H, R'= CH3
VIIa, R= H, R'= CH3
, R= 8-OCH3, R'= CH3
, R= 8-OCH3, R'= C6H5
, R= 8,9-diOCH3, R'= CH3
, R= 8,9-diOCH3, R'= C6H5
b
c
d
e
, R= 8-OCH3, R'= CH3
, R= 8-OCH3, R'= C6H5
, R= 8,9-diOCH3, R'= CH3
, R= 8,9-diOCH3, R'= C6H5
b
c
d
e
N-Alkyl pyridinium (II) and N-alkyl isoquinolinium salts V undergo cyclization reaction when heated with
sodium bicarbonate to give the corresponding indolizine derivatives III and VI, respectively, which undergo
ring opening and recyclization reactions when heated with aqueous sodium hydroxide to give the corresponding
indole derivatives IV and IX, respectively. Molecular modeling tools including Molecular Mechanics using
Augmented MM3 parameters followed by geometry optimization calculations in MO-G using PM3 parameters
were performed to gain better understanding and more insights on the thermodynamic properties of the recycli-
zation reactions of compounds IIa–g to the corresponding IIIa–g and IIIa–g to the corresponding IVa–g. The
results were in excellent agreement with the experimental data and hence were proven to be a good tool in
explaining different yields % because of the steric and electronic effects of electron-withdrawing groups on
the reactivity of the pyridine ring for nucleophilic attack.
J. Heterocyclic Chem., 50, 638 (2013).
INTRODUCTION
RESULTS AND DISCUSSION
Fadda and coworkers [1–9] have reported the recyclization
of N-alkyl pyridinium salts in the presence of aqueous alkali,
alkyl amine or alkyl ammonium sulphite to give the
corresponding aminobiphenyl derivatives. The nature and po-
sition of substituents in the pyridine ring have a considerable
effect on these types of reactions [10]. It was expected that
2-benzylpyridinium salts that have an alkyl radical in different
positions in the pyridine ring would undergo recyclization
reaction. The use of pyridinium salts in the organic syntheses
is now receiving a considerable interest. As a part of our pro-
gram directed to develop a new, simple, and efficient method-
ology for the synthesis of new aromatic compounds using
readily available pyridinium salts, the enamine rearrangement
[1–10] appears to be a fundamental type of pyridine-into-
benzene ring transformation. The important purpose of this
original work is to study the reactions of such pyridinium salts,
which might be extended to include and develop a new meth-
odology for the synthesis of some new indole derivatives that
are expected potential biological activity. In addition, it is
planned to evaluate the biological activity of the newly synthe-
sized compounds as antitumor and antischistosomal agents.
In the present study, the action of aqueous sodium bicar-
bonate on N-alkylpyridinium salts IIa–g led to the formation
of indolizine derivatives IIIa–g (Chichibabin reaction)
(Scheme 1).
In this reaction, it was noticed that the yield of IIIe (31%)
was less than half of IIIa (70%) probably because of the
steric effect of the t-butyl group that resists cyclization to
1
the indolizine IIIe. The H NMR spectrum of 2-methyl-6-
nitroindolizine (IIIa) showed singlet signal at d 8.31ppm
because of H-5 of pyridine ring. This signal was observed
in all indolizine compounds having free 5-position. This
low field signal of H-5 in IIIa is attributed to the presence
of electron acceptor nitro group in position 6. In addition,
signal at d 6.77ppm is corresponding to H-3 and not for
H-7 or H-8; protons H-7 and H-8 were observed at d 7.05–
7.40ppm as multiplet signal, whereas signal appeared as
1
singlet at d 6.2 ppm is due to H-1. The H NMR spectrum
of 2-methyl-8-nitroindolizine (IIIc) showed a triplet at
d 6.95 ppm for 6-H as a result of the interaction with H-5
and H-7. Other signals were observed at d 6.75 as singlet sig-
nal for 3-H, where signals at d 6.65 is due to H-1, d 7.83 as
© 2013 HeteroCorporation

May 2013
Enamine Rearrangement of Pyridinium Salts to Indole Ring
639
Scheme 1. Synthesis of indolizine derivatives IIIa–g.
R
R
R
N
CH3
N
N
CH3
R'
Br
CH2COR'
Ia, R= 5-NO2
b, R= 3-NO2
c, R= 6-F
IIa, R= 5-NO2, R'= CH3
b, R= 5-NO2, R'= C6H5
c, R= 3-NO2, R'= CH3
d, R= 3-NO2, R'= C6H5
e, R= 5-NO2, R'= CH(CH3)3
f, R= 6-F, R'= CH3
IIIa, R= 6-NO2, R'= CH3
b, R= 6-NO2, R'= C6H5
c, R= 8-NO2, R'= CH3
d, R= 8-NO2, R'= C6H5
e, R= 6-NO2, R'= CH(CH3)3
f, R= 5-F, R'= CH3
g, R= 6-F, R'= C6H5
g, R= 5-F, R'= C6H5
doublet for 5-H (J5,6 = 8 Hz), d 7.79 for H-7 (J7,6 =8Hz), and
finally at d 2.22 as singlet signal for CH3 protons. On the other
hand, the H NMR spectrum of 2-methyl-5-fluoroindolizine
effect of t-butyl group that resists cyclization to the indolizine
in the latter (Table 1).
1
It has been found that the presence of a nitro group in
position 6 in the pyridine ring of indolizine will increase
the reactivity of position 5 toward nucleophilic attack. Thus,
treatment of all the indolizine compounds IIIa–g with aque-
ous alcoholic sodium hydroxide afforded the corresponding
indole derivatives IVa–g. It is worth noting that 2-methyl-
6-nitroindolizines and 2-phenyl-6-nitroindolizines IIIa, b
gave the corresponding nitroindoles in 85 and 90%
yields, respectively, whereas 2-methyl-8-nitroindolizines
(IIIf) showed three singlet signals at d 2.2, 6.08, and
6.88 ppm attributable to CH3, 1-H, and 3-H, respectively.
Other signals were observed at d 6.22 as multiplet for H-6,
6.82 as multiplet for H-7, and d 7.23 as multiplet for H-8.
The mass spectrum of nitroindolizine showed the molecular
ion peak as base peak and showed fragments because of
(M-NO)+ and (M-NO2)+. These results are in agreement
with those reported earlier for indolizine having electron
acceptor group [11].
and 2-phenyl-8-nitroindolizines IIIc,
d afforded the
To gain better understanding of the reaction thermodynam-
ics of the reaction leading to the formation of compounds
IIIa–g, the structures of the reactants IIa–g and products
IIIa–g were refined by performing optimize geometry calcula-
tions in Molecular Mechanics using Augmented MM3 para-
meters followed by geometry optimization calculations in
MO-G using PM3 parameters. Table 1 shows the total heat
of formation for compounds IIa–g and IIIa–g and the stabili-
zation energy (ΔE) for each cyclization reaction. The data in
Table 1 demonstrate clearly that all cyclization reactions of
IIa–g to IIIa–g are exothermically driven. Moreover, the
ΔE of the cyclization of compound IIa to compound IIIa is
1.833 kcal lower than that of compounds IIe to IIIe, which
explains the greater % yield of the former, owing to the steric
corresponding nitroindoles in 40 and 48% yields, respectively.
These results show that the nitro group at position 8 in the
pyridine ring of indolizine decreases the reactivity at C-5
toward nucleophilic attack and consequently decreases the
yield of the recyclization product.
Moreover, the recyclization of the fluoroindolizines IIIf, g
afforded the corresponding indole derivatives IVf, g, upon
treatment with the same aforementioned base, in lower yields
30 and 34%, respectively. These results may be due to the
steric effect of the fluorine atom in position 5 that resists
the step of hydrolytic solvolysis and consequently the recrys-
tallization reaction to give the corresponding indole deriva-
tives IVf, g. In addition, treatment of the aforementioned
indolizines IIIa–g with sodium ethoxide in ethanol or with
Table 1
Calculated (MM3/PM3 parameters) heats of formation and stabilization energies (ΔE) of recyclization reactions of compounds IIa–g to the corresponding IIIa–g.
Compound
E (kcal/mol)
Compound
kcal/mol
ΔE(kcal/mol)
IIa
IIb
IIc
IId
IIe
IIf
142.2305
175.7517
146.7033
176.5561
126.1100
105.4314
128.8626
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
32.6232
66.3819
34.9058
68.4451
18.3369
À1.6568
31.8391
À109.607
À109.3698
À111.7975
À108.111
À107.7731
À107.0882
À127.0235
IIg
IIIg
E = total heat of formation; stabilization energy = ΔE = Eproduct À Ereactant
.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

640
A. Hosaan and A. A. Fadda
Vol 50
Table 2
aqueous potassium hydroxide led to the indole derivatives in
very poor yields, whereas heating with sodium methoxide
failed to effect recrystallization. The rearrangement of indo-
lizines IIIa–g to indole derivatives IVa–g can be considered
as a new route for indoles bearing an alkyl or aryl groups in
position 3. Such indoles, especially 7-nitroindole derivatives
IVc, d are difficult to be prepared by any known methods,
have been prepared by the aforementioned route. The recy-
clization of indolizines IIIa–g to indole derivatives IVa–g
may take place following the mechanism as shown in
Scheme 2.
Calculated (MM3/PM3 parameters) heats of formation and stabilization
energies (ΔE) of recyclization reactions of compounds IIIa–g to the
corresponding IVa–g.
Compound E (kcal/mol) Compound kcal/mol ΔEt(kcal/mol)
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
32.6232
66.3819
34.9058
68.4451
18.3369
À1.6568
31.8391
IVa
IVb
IVc
IVd
IVe
IVf
22.0271 À10.596
55.6721 À10.7098
22.5452 À12.3606
55.2858 À13.1593
8.0650 À10.2719
À9.9453
À8.2885
À5.9913
IIIg
IVg
25.8478
To gain insights on the thermodynamics of the recycliza-
tion of compounds IIIa–g to compounds IVa–g, Molecular
Mechanics using Augmented MM3 parameters followed by
geometry optimization calculations in MO-G using PM3
parameters were performed to calculate the total heat of
formation for the equilibrium molecular geometry of com-
pounds IVa–g. Table 2 shows the ΔE for the recyclization
of IIIa–g to the corresponding IVa–g, which confirms that
all recyclization reactions are thermodynamically favorably
driven. The data in Table 2 show clearly that the ΔE for
the recyclization of IIIa, b to the corresponding IVa, g are
less thermodynamically favorable than that of IIIc, d to the
corresponding IVc, d because the presence of the nitro group
at position 6 in the pyridine ring of the indolizines (IIIa, b)
exerts steric effect for the nucleophilic attack to take place
effectively at C-5, which explains the lower % yield for
compounds IVa–b compared with compounds IVc, d.
Moreover, the data in Table 2 show that the ΔE for the
recyclization of IIIf, g to the corresponding IVf, g are the
lowest thermodynamically favorable compared with com-
pounds IVa–d, which explains why they had the lowest %
yield owing to the steric effect exerted by the fluorine
E = total heat of formation; ΔE = stabilization energy = Eproduct À Ereactant
.
atom at C-5 that resists the step of hydrolytic solvolysis
and accordingly the recyclization reaction to furnish the
corresponding indole derivatives IVf, g. Moreover, in com-
pounds IIIa–d, the nitro group posses more electron-
withdrawing power than the F atom in compounds IIIg, h,
which leads to a more electron-deficient center at C-5 favor-
ing stronger nucleophilic attack and effective recyclization
reactions to the corresponding indole derivatives (Table 2).
The structure of the intermediate s-complex was estab-
lished on the basis of NMR data. It seems that the NMR
spectra of s-complexes (A) and (B) are the same in which
there are two doublets for H-6 and H-7 in case of (A) and
for H-5 and H-6 in case of (B).
1
Thus, from the H NMR study of both indolizine com-
pounds and s-complex, we can see that the OH ion is added
to C-5 and not C-7 to form the intermediate s-complex (A)
(Figure 1).
Moreover, when 1,3-dialkylisoquinolinium salts VIa–d
when heated in water–alcohol alkali afforded the corresponding
Scheme 2. Mechanism of formation of indole derivatives IVa–g.
X
X
X
OH
N
HO
X
N
N
R'
R'
R'
HO
H
H
X
H
X
R'
R'
-OH
N
R'
N
H
IVa-g
N
HO
H
IVa, R'= 3-CH3, X= 5-NO2
b, R'= 3-C6H5, X= 5-NO2
c, R'= 3-CH3, X= 7-NO2
d, R'= 3-C6H5, X= 7-NO2
e, R'= 3-C(CH3)3, X= 5-NO2
f, R'= 3-CH3, X= 4-F
g, R'= 3-C6H5, X= 4-F
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2013
Enamine Rearrangement of Pyridinium Salts to Indole Ring
641
then followed by ring closure and the C-C bond formation
(such as the mechanism of the rearrangement of indolizines
to indoles) (Scheme 4).
NO2
NO2
H
HO
1
The H NMR spectrum of 1-methyl-3H-benzo[e]indole
N
H
N
CH3
CH3
IXa showed three singlet signals at d 2.3, 7.1, and 9.9 ppm
attributable to CH3, H-2, and NH protons, respectively, and
two doublets at d 7.3 and 7.6 ppm because of H-4 and H-5
protons.
HO
(A)
(B)
Figure 1. Structure of the intermediate s-complexes (A) and (B) of indolizine
compounds.
CONCLUSION
2-methylpyrrolo[2,1-a]isoquinoline derivatives VIIa–d in
40–80% yields (Scheme 3).
The H NMR spectrum of 1-methyl-2-(2-oxopropyl)
The evidence on the pyridine ring recyclization available
at present concerns primarily the formation of heterocycles
and carbocycles, which is quite natural considering the high
solvolysability of the N═CH bond in pyridinium salts. Some
of these reactions are significant as preparative methods. The
enamine rearrangement of pyridinium salts into aromatic
amines described by Fadda et al. is a new type of recycliza-
tion. The information on the structural factors and reaction
conditions obtained so far promises to provide new exciting
results. The recyclization of pyridine derivatives not acti-
vated by quaternization is relatively scarce. Because of the
insufficient polarization of the aromatic ring in this case,
the nucleophilic attack is nonselective, and the C-C as well
as C-N bond cleavage takes place.
1
isoquinolinium bromide VIa showed two singlet signals at d
2.2, 2.93, and 5.95 ppm because of COCH3, CH3, and CH2
protons, respectively, and two doublets at d 8.5 and
8.91 ppm because of H-3 and H-4, respectively, whereas the
1H NMR spectrum of 2-methylpyrrolo[2,1-a]isoquinoline
VIIa showed three singlet signals at d 2.01, 6.0, and
6.8 ppm attributable to CH3, H-1, and H-3 (pyrrole ring) and
two doublets at d 7.5 and 8.4 ppm because of H-5 and H-6.
This reaction, too, begins with the nucleophilic attack by the
hydroxide anion directed at the carbon atom by the aromatic
nitrogen. The next stage is the ring opening (probably accord-
ing to the electrocyclic mechanism) by C-N bond fission. It is
Scheme 3. Synthesis of pyrrolo[2,1-a]isoquinoline derivatives VIIa–e.
O
R'COCH2Br
OH
R
R
N
N
N
R'
R
Br
CH3
CH3
VIa-e
Va-c
VIIa-e
VIIa, R= H, R'= CH3
b, R= 8-OCH3, R'= CH3
c, R= 8-OCH3, R'= C6H5
d, R= 8,9-diOCH3, R'= CH3
e, R= 8,9-diOCH3, R'= C6H5
R'
Va, R= H
b, R= 6-OCH3
c, R= 6,7-diOCH3
VIa, R= H, R'= CH3
b, R= 6-OCH3, R'= CH3
c, R= 6-OCH3, R'= C6H5
d, R= 6,7-diOCH3, R'= CH3
e, R= 6,7-diOCH3, R'= C6H5
Scheme 4. Synthetic route of formation of benzoindole derivatives IXa–e.
OH
OH
OH
H
R
N
N
NH
R
R
R'
IXa-e
IXa, R= H, R'= CH3
VIIa-e
VIIIa-e
R'
R'
b, R= 8-OCH3, R'= CH3
c, R= 8-OCH3, R'= C6H5
d, R= 8,9-diOCH3, R'= CH3
e, R= 8,9-diOCH3, R'= C6H5
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

642
A. Hosaan and A. A. Fadda
Vol 50
N-Phenacyl-5-nitro-2-methylpyridine (IIb).
70%; mp
Molecular modeling tools using Molecular Mechanics,
189–190ꢀC; Calcd for C14H15BrN2O3: C, 49.8; H, 4.1; N, 8.3.
Found C, 49.7; H, 4.0; N, 8.1.
MM3 parameters, and Quantum Mechanics, PM3 para-
meters were proven to be effective tools in understanding
the thermodynamics of cyclization/recyclization reactions
and explaining the different % yields because of differ-
ences in steric effects and/or electronic properties.
N-Phenacyl-3-nitro-2-methylpyridine (IId). 80%; mp
160–161ꢀC; Calcd for C14H13BrN2O3: C, 49.87; H, 3.89; N,
8.31. Found C, 49.6; H, 3.7; N, 8.27.
N-Phenacyl-6-fluoro-2-methylpyridine (IIg). 60%; mp
126ꢀC; Calcd for C14H13BrFNO: C, 54.21; H, 4.22; N, 4.52.
Found C, 54.01; H, 4.03; N, 4.35.
N-Pinaconyl-2-methyl-5-nitropyridinium bromide (IIe).
Formation of 4-bromo-2,2-dimethylbutan-3-one. To pinacolone
[14], 0.014 g (0.14 mmol), anhydrous ether (200mL) at 0ꢀC was
added drop by drop bromine 0.022g (0.14 mmol). After complete
addition, the solution turned yellow in color. The reaction mixture
was then poured into ice cold water (100 mL) and then extracted
with diethyl ether. The ethereal extract was then dried over
sodium sulfate and evaporated in vacuo to give 63% yield, boiling
point 80–82ꢀC/12mL [14].
EXPERIMENTAL
Molecular modeling. The equilibrium molecular geometry of
the compounds IIa–g, IIIa–g, and IVa–g was predicted in Molecular
Mechanics using Augmented MM3 parameters followed by
geometry optimization calculations in MO-G using PM3
parameters, and the total heat of formation (E) for each compound
and the stabilization energy (ΔE) of each cyclization/recyclization
reaction were calculated. All calculations were run in Scigress
Explorer Professional Version 7.7.0.47, on an Intel(R) Core
(TM)2 Quad, CPU Q6600 @2.4 GHz with 3.5 G of RAM.
MLR was used.
Formation of IIe. A mixture of Ia 0.21 g (1.5 mmol) and
4-bromo-2,2-dimethylbutan-3-one was dissolved in acetophenone
or ethyl methyl ketone (1 mL). The reaction mixture is then heated
at 120ꢀC for 20 h (or heated in pressure tube at 70–80ꢀC for 3h).
The obtainable crystals on cooling are washed and crystallized from
acetone to give IIe. 35%, mp 241ꢀC; Calcd for C12H17BrN2O3: C,
45.44; H, 5.40; N, 8.83. Found C, 45.35; H, 5.37; N, 8.77.
Synthesis.
All melting points are (uncorrected) in degree
centigrade and were determined on Gallenkamp electric
melting point apparatus (Electronic Melting Point Apparatus,
London, Great Britain). The reaction products were shown to
be single entity by thin layer chromatography (TLC) in
benzene. The infrared spectra were recorded in potassium
bromide disks on a pye Unicam SP 3300 and Shimadzu FT IR
8101 PC infrared spectrophotometers (Pye Unicam Ltd.,
Cambridge, England and Shimadzu, Tokyo, Japan,
respectively). The 1H NMR and 13C NMR spectra were
recorded on a Varian Mercury VX-300 NMR spectrometer
(USA) at 300 and 75 MHz, respectively. Chemical shifts were
related to that of the solvent. The mass spectra were recorded
on a Shimadzu GCMS-QP 1000 EX (Japan) mass spectrometer at
70eV. Elemental analyses were recorded on PERKIN-ELMER
2400 Elemental analyzer at the Microanalytical Center at Cairo
University, Cairo, Egypt.
Formation of indolizine derivatives IIIa–g.
General
procedure. A mixture of II (5 mmol) and sodium bicarbonate
1.0 g (12 mmol) in absolute ethanol (20mL) was heated with
continuous stirring for 1–3 h. The reaction mixture was filtered,
the filtrate evaporated in vacuo, and the residue recrystallized from
heptanes under cooling to give IIIa–g.
2-Methyl-6-nitroindolizine (IIIa).
70%; mp 85–87ꢀC
(crystallization from hexane or heptanes); IR: 1560 (C═C), 1530,
1
1350 cmÀ1 (NO2); H NMR (300 MHz, DMSO-d6): d 2.0 (s, 3H,
CH3), 6.2 (s, 1H, H-1), 6.77 (s, 1H, H-3), 7.05–7.40 (m, 2H, H-7,
H-8), 8.31 ppm (s, 1H, H-5); 13C NMR (75MHz, DMSO-d6): d
140.8, 130.7, 124.6, 121.3, 121.2, 112.6, 111.8, 103.6, 20.4 ppm;
MS: m/z (%): 176 (100.0), 131 (7.2), 130 (80), 128 (5.0), 118
(3.0), 103 (35.0), 102 (10.0), 77 (40.0), 63 (5.0), 51 (15.0).
Calcd for C9H8N2O2. C, 61.36; H, 4.58; N, 15.90. Found C,
61.2; H, 4.5; N, 15.8.
2-Methyl-5-nitropyridine (Ia). It was prepared according to
the procedure reported earlier [12], 63%, mp 110–111ꢀC.
2-Methyl-3-nitropyridine (Ib). It was obtained according to
the previously reported work [13], 86%, mp 23–24ꢀC, bp 84–86/
5 mm.
2-Phenyl-6-nitroindolizine (IIIb).
80%; mp 203–204ꢀC
(crystallization from ethanol); IR: 1562 (C═C), 1530–1350 cmÀ1
1
2-Fluoro-6-methylpyridine (Ic). It was supplied by Aldrich
(NO2); H NMR (300 MHz, DMSO-d6): d 6.8 (s, 1H, H-1), 7.1
[407–22–7] code no., bp 140ꢀC.
(s, 1H, H-3), 7.37 (d, 1H, H-8), 7.4–7.52 (m, 5H, Ar-H), 7.8
(d, 1H, H-7), 8.37ppm (s, 1H, H-5); 13C NMR (75 MHz, DMSO-
d6): d 140.6, 136.6, 130.5, 130.3, 129.8, 129.3, 129.1, 128.0,
127.4, 121.3, 121.2, 112.8, 109.4, 98.1ppm; MS: m/z (%): 238
(100.0), 193 (20), 192 (70), 191 (30), 190 (10), 180 (15.5), 165
(30.1), 164 (12.2), 163 (10.5), 115 (10.5). Calcd for C14H10N2O2.
C, 70.58; H, 4.23; N, 11.76. Found C, 70.63; H, 4.26; N, 11.83.
Formation of N-acetonyl pyridinium salts IIa, c, f.
General
procedure. A mixture of Ia, c, f (3 mmol) and o-bromoacetone
(3.5 mmol) in acetone (5 mL) was refluxed at 60–80ꢀC on a water
bath for 10–15 h. The resultant solid was filtered and
recrystallized from ethanol to give IIa, f. Compound IIc did not
separate, and therefore, it could not be crystallized.
N-Acetonyl-5-nitro-2-methylpyridine (IIa). 78%; mp 165–
166ꢀC; IR: 1710 (CO), 1620 cmÀ1 (C═N); Calcd for C9H11BrN2O3:
C, 39.3; H, 4.1; N, 10.2. Found C, 39.4; H, 4.1; N, 10.1.
N-Acetonyl-6-fluoro-2-methylpyridine (IIf). 64%; mp 102–
104ꢀC; Calcd for C9H11BrNOF: C, 43.8; H, 4.5; N, 5.6. Found C,
43.6; H, 4.3; N, 5.4.
2-Methyl-8-nitroindolizine (IIIc).
A mixture of 2-methyl-3-
nitropyridine 0.5 g (3.6 mmol) and bromoacetone 2 g (14.4 mmol)
was heated at 90ꢀC for 6 h. The resultant mass was acidified with
dil. HCl to pH 2–3, heated again, and filtered while hot. Sodium
bicarbonate was added to the hot filtrate and heated to boiling. The
reaction mixture was extracted with chloroform. The chloroform
extract was dried on magnesium sulfate and matographed over
silica gel column by using chloroform as eluent to give IIIc. 36%;
Formation of N-phenacyl pyridinium salts IIb, d, g.
General
procedure.
A mixture of Ib, d, g (3.6 mmol) and phenacyl
1
bromide (5 mmol) in acetone (3 mL) was refluxed at 90ꢀC on a
water bath for 9 h. The resultant solid was filtered and
recrystallized from ethanol to give IIb, d, g.
mp 101–103ꢀC (crystallization from hexane); H NMR (300 MHz,
DMSO-d6): d 2.22 (s, 3H, CH3), 6.65 (s, 1H, H-1), 6.75 (s, 1H,
H-3), 6.95 (t, 1H, H-6), 7.79 (d, 1H, H-7, J7,6 = 8 Hz), 7.83 ppm
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2013
Enamine Rearrangement of Pyridinium Salts to Indole Ring
643
(d, 1H, H-5, J5,6 =8Hz); 13C NMR (75 MHz, DMSO-d6): d 139.8,
130.1, 129.7, 124.1, 113.7, 112.5, 111.9, 103.7, 20.3 ppm; MS:
m/z (%): 176 (100.0), 131 (8.5), 130 (90.5), 129 (15.2), 128
(14.3), 110 (10.5), 109 (12.2), 103 (10.2), 91 (40.5), 77 (30.2),
69 (10.2). Calcd for C9H8N2O2. C, 61.36; H, 4.58; N, 15.90.
Found C, 61.1; H, 4.4; N, 15.8.
(q, 1H, H-6, J6,4 = 2 Hz, J6,7 = 9 Hz), 8.66 (d, 1H, H-4, J4,6 = 2 Hz),
10.2ppm (s, 1H, NH); 13C NMR (75 MHz, DMSO-d6): d 142.6,
136.7, 132.8, 130.3, 129.6, 129.5, 128.1, 127.7, 127.4, 124.9,
114.3, 112.6, 111.4ppm; MS: m/z (%): 238 (100.0), 192 (35), 165
(70), 164 (15), 97 (10.2), 83 (20), 71 (20), 69 (30), 57 (50), 55 (40).
3-Methyl-7-nitroindole (IVc).
40%; mp 139–141ꢀC
1
2-Phenyl-8-nitroindolizine (IIId).
86%; mp 172–173ꢀC
(crystallization from benzene); H NMR (300MHz, DMSO-d6):
d 2.34 (s, 3H, CH3), 7.07 (t, 1H, H-5, H-7, J5,6 = J5,4 = 8 Hz), 7.13
(s, 1H, H-2), 7.93 (t, 2H, H-4, H-6, J6,5 = J4,6 = 8 Hz), 10.2 ppm
(s, 1H, NH); 13C NMR (75 MHz, DMSO-d6): d 136.4, 130.8,
128.4, 125.6, 123.4, 122.8, 114.7, 111.1, 17.2ppm; MS: m/z (%):
176 (100.0), 175 (50), 130 (64.5), 129 (30), 128 (10), 103 (35),
102 (15), 76 (10), 75 (5), 51 (10). Calcd for C9H8N2O2. C, 61.36;
H, 4.58; N, 15.9. Found C, 61.29; H, 4.49; N, 15.84.
(crystallization from heptane); 1H NMR (300MHz, DMSO-d6):
d 6.94 (m, 1H, H-6), 7.4–7.58 (m, 5H, C6H5), 7.61 (s, 1H,
H-3), 7.81 (s, 1H, H-1), 8.28, 8.58 ppm (d, d, 2H, H-7,
J7,6 =8Hz, H-5, J5,6 =8Hz); 13C NMR (75MHz, DMSO-d6): d
141.3, 137.4, 130.9, 130.8, 129.6, 129.4, 129.3, 128.9, 114.1,
113.4, 97.5 ppm; MS: m/z (%): 238 (100.0), 192 (60.5), 191
(55), 190 (12.2), 165 (20.5), 128 (20), 91 (15), 78 (38), 69 (15),
63 (15). Calcd for C14H10N2O2. C, 70.58; H, 4.23; N, 11.76.
Found C, 70.45; H, 4.15; N, 11.66.
3-Phenyl-7-nitroindole (IVd).
48%; mp 156–158ꢀC
(crystallization from heptane); 13C NMR (75 MHz, DMSO-d6):
d 137.1, 136.8, 130.7, 130.1, 130.0, 129.8, 129.5, 127.8, 127.3,
125.7, 125.1, 123.3, 114.2, 110.9 ppm; MS: m/z (%): 238
(M+, 100.0), 192 (40), 191 (20), 190 (20), 165 (31), 164
(10), 163 (10), 128 (10), 91 (10). Calcd for C14H10N2O2. C,
70.58; H, 4.23; N, 11.76. Found C, 70.36; H, 4.18; N, 11.66.
3-t-Butyl-7-nitroindole (IVe). 27%; mp 210ꢀC (crystallization
from benzene); 1H NMR (300 MHz, DMSO-d6): d 1.4 (s, 9H,
3CH3), 7.2 (s, 1H, H-2), 7.57 (t, 1H, H-6, J6,5 = J6,4 = 8 Hz), 7.99
(d, 1H, H-4, J4,6 = 8 Hz), 8.11 (d, 1H, H-5, J5,6 = 8 Hz), 10.2 ppm
(s, 1H, NH); 13C NMR (75 MHz, DMSO-d6): d 142.6, 132.5,
128.5, 127.3, 124.8, 123.5, 114.0, 112.4, 42.6, 32.7ppm; MS: m/z
(%): 218 (M+, 100.0), 219 (M+ + 1, 15), 220 (M+ + 2, 5). Calcd
for C12H14N2O2. C, 66.04; H, 6.47; N, 12.84. Found C, 66.0; H,
6.26; N, 12.73.
2-t-Butyl-6-nitroindolizine (IIIe).
31%; mp 92–94ꢀC
(crystallization from heptane); 1H NMR (300MHz, DMSO-d6):
d 1.38 (s, 9H, 3CH3), 6.1 (s, 1H, H-1), 6.8 (s, 1H, H-3), 6.98
(m, 1H, H-6), 7.43 (d, 1H, H-7), 7.83 ppm (d, 1H, H-5); 13C
NMR (75 MHz, DMSO-d6): d 140.8, 130.7, 124.5, 120.5, 120.3,
112.4, 111.9, 105.2, 39.1, 24.3 ppm; MS: m/z (%): 218 (90.5),
204 (15), 203 (100.0), 176 (5.5), 157 (15), 156 (10), 130 (10), 128
(15), 115 (10), 90 (10). Calcd for C12H14N2O2. C, 66.04; H, 6.47;
N, 12.84. Found C, 66.0; H, 6.3; N, 12.7.
2-Methyl-5-fluoroindolizine (IIIf).
30%; mp 126ꢀC
(crystallization from heptane); 1H NMR (300 MHz, DMSO-d6):
d 2.2 (s, 3H, CH3), 6.08 (s, 1H, H-1), 6.22 (m, 1H, H-6), 6.82
(m, 1H, H-7), 6.88 (s, 1H, H-3), 7.23 ppm (m, 1H, H-8); 13C
NMR (75MHz, DMSO-d6): d 140.7, 132.8, 124.6, 123.5, 118.6,
11.6, 105.2, 98.6, 19.6ppm; MS: m/z (%): 149 (M+, 100.0), 150
(M+ + 1, 10). Calcd for C9H8FN. C, 72.47; H, 5.41; N, 9.39.
Found C, 72.35; H, 5.33; N, 9.25.
3-Methyl-4-fluoroindole (IVf).
30%; mp 127129ꢀC
(crystallization from heptane); 1H NMR (300MHz, DMSO-d6):
d 2.31 (s, 3H, CH3), 7.01 (d, 1H, H-5, J5,6 = 8 Hz), 7.09 (m, 2H,
H-6, J6,5 =J6,7 =8Hz, H-7, J7,6 = 8 Hz), 7.21 (s, 1H, H-2),
10.21 ppm (s, 1H, NH); 13C NMR (75 MHz, DMSO-d6): d 154.7,
138.4, 123.6, 122.0, 121.2, 119.4, 116.8, 111.3, 107.5, 21.6 ppm;
MS: m/z (%): 149 (M+, 100.0), 150 (M+ + 1, 10.5). Calcd for
C9H8FN. C, 77.47; H, 5.41; N, 9.39. Found C, 77.39; H, 5.33; N,
9.28.
2-Phenyl-5-fluoroindolizine (IIIg).
34%; mp 163–161ꢀC
(crystallization from heptane); 13C NMR (75 MHz, DMSO-d6):
d 141.2, 137.5, 131.6, 131.2, 130.7, 130.2, 129.8, 129.1, 127.4,
123.4, 120.2, 109.3, 97.8, 97.7 ppm; MS: m/z (%): 211 (M+, 100.0),
212 (M+ + 1, 15.5), 213 (M+ + 2, 2.1). Calcd for C14H10FN.
C, 79.60; H, 4.77; N, 6.63. Found C, 79.51; H, 4.63; N,
6.49.
3-Phenyl-4-fluoroindole (IVg). 34%; mp 213ꢀC (crystallization
1
from heptane); H NMR (300 MHz, DMSO-d6): d H-5, H-6 and
Rearrangement of IIIa–g to indole derivatives IVa–g.
H-7 gave signals like that of IVf; on the other hand, H-2 appeared
at d 8.4 ppm (s, 1H); 13C NMR (75 MHz, DMSO-d6): d 155.0,
137.9, 136.8, 129.6, 129.2, 128.3, 124.9, 122.4, 115.8, 113.7, 110.4,
106.8 ppm; MS: m/z (%): 211 (M+, 100.0), 212 (M+ + 1, 20), 213
(M+ +2, 5). Calcd for C14H10FN. C, 79.60; H, 4.77; N, 6.63. Found
C, 79.49; H, 4.63; N, 6.49.
General procedure.
Compound IIIa 0.2 g (1.15 mmol),
IIIb 0.27 g (1.15 mmol), IIIc 0.2 g (1.15 mmol), IIId 0.27 g
(1.15 mmol), IIIe 0.23 g (1.15 mmol), IIIf 0.17 g (1.15 mmol),
or IIIg 0.24 g (1.15 mmol) was refluxed with alcoholic potassium
hydroxide (10 mL ethanol, 10% H2O, 2 g KOH) in atmospheric
argon for 5–15 h. The reaction mixture was then poured into
100 mL of water. The obtainable precipitate was filtered off and
washed with water to give IV as a yellow material.
The s-complex (A) could be isolated after adding sodium
hydroxide to indolizine; it precipitated out on cold.
85%; mp 125–127ꢀC
Formation of N-acetonyl and N-phenacyl isoquinolinium
3-Methyl-5-nitroindole (IVa).
salts (VIa–e).
It has been prepared according to the general
(crystallization from xylene); IR: 3325 (NH), 1530 (Antisymm.
1
NO2), 1350 cm–1 (Symm. NO2); H NMR (300 MHz, DMSO-d6):
method for preparing salts IIa, c, f.
N-Acetonyl-1-methylisoquinolinium bromide (VIa).
80%;
d 2.3 (s, 3H, CH3), 7.18 (s, 1H, H-2), 7.37 (d, 1H, H-7, J7,6 =9Hz),
7.9 (q, 1H, H-6, J6,4 =2Hz, J6,7 = 9 Hz), 8.46 (d, 1H, H-4,
J4,6 = 2 Hz), 10.1 ppm (s, 1H, NH); 13C NMR (75 MHz, DMSO-d6):
d 142.6, 132.5, 129.4, 128.9, 123.1, 114.6, 112.3, 111.4, 17.4 ppm;
MS: m/z (%): 176 (100.0), 175 (16), 130 (75), 129 (25), 103 (35),
102 (12.4), 77 (30), 69 (15), 57 (16), 55 (10). Calcd for C9H8N2O2.
C, 61.36; H, 4.58; N, 15.9. Found C, 61.21; H, 4.53; N, 15.8.
mp 9294ꢀC (washed by ether); IR: 1725 (CO), 1620cmÀ1
(C═N); Calcd for C13H14BrNO. C, 55.73; H, 5.04; N, 5.0. Found
C, 55.62; H, 4.88; N, 5.0.
N-Acetonyl-1-methyl-6-methoxyisoquinolinium bromide
(VIb).
76%; mp 162164ꢀC (crystallization from
heptane). Calcd for C14H16BrNO2. C, 54.21; H, 5.20; N,
4.52. Found C, 54.16; H, 5.13; N, 4.48.
3-Phenyl-5-nitroindole (IVb).
90%; mp 190–192ꢀC; Lit.,
mp 187ꢀC [15] (crystallization from benzene); 1H NMR
N-Phenacyl-1-methyl-6-methoxyisoquinolinium bromide
(VIc).
82%; mp 180–182ꢀC (crystallization from heptane);
(300 MHz, DMSO-d6): d 7.2–7.7 (m, 7H, C6H5, H-2, H-7), 8.02
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

644
A. Hosaan and A. A. Fadda
Vol 50
Calcd for C19H18BrNO2. C, 61.30; H, 4.87; N, 3.76. Found C,
124.7, 124.6, 122.3, 118.9, 118.5, 117.8, 39.4, 38.7, 17.4 ppm; MS:
m/z (%): 181 (M+, 100.0). Calcd for C13H11N. C, 86.15; H, 6.12;
N, 7.73. Found C, 86.10; H, 6.11; N, 7.65.
61.25; H, 4.80; N, 3.65.
N-Acetonyl-1-methyl-6,7-dimethoxyisoquinolinium bromide
(VId).
63%; mp 210212ꢀC (crystallization from heptane).
8-Methoxy-1-methyl-3H-benzo[e]indole (IXb).
82%; mp
262–264ꢀC (crystallization from heptane); 1H NMR (300MHz,
DMSO-d6): d 2.3 (s, 3H, CH3), 3.83 (s, 3H, OCH3), 7.1 (s, 1H,
H-2), 7.24 (d, 1H, H-7, J7,6 = 8 Hz), 7.32 (d, 1H, H-4, J4,5 = 8 Hz),
7.39 (s, 1H, H-9), 7.60 (d, 1H, H-5, J5,4 = 8 Hz), 8.10 (d, 1H, H-6,
J6,7 = 8 Hz), 10.2ppm (s, 1H, NH); 13C NMR (75 MHz, DMSO-
d6): d 150.4, 134.8, 127.8, 1275, 123.5, 123.2, 118.7, 118.3,
117.9, 117.2, 99.7, 53.6, 40.5, 17.4 ppm; MS: m/z (%): 211
(M+, 100.0), 212 (M+ + 1, 25). Calcd for C14H13NO. C, 79.59;
H, 6.2; N, 6.63. Found C, 79.39; H, 6.10; N, 6.48.
Calcd for C15H18BrNO3. C, 52.96; H, 5.33; N, 4.12. Found C,
52.77; H, 5.25; N, 4.10.
N-Phenacyl-1-methyl-6,7-dimethoxyisoquinolinium bromide
(VIe).
72%; mp 189–191ꢀC (crystallization from heptane).
Calcd for C20H20BrNO3. C, 59.71; H, 5.01; N, 3.48. Found C,
59.65; H, 4.89; N, 3.35.
Formation of pyrrolo[2,1-a]isoquinolines VIIa–e.
It has
been prepared according to the general procedure for indolizine
formation.
2-Methylpyrrolo[2,1-a]isoquinoline (VIIa).
64%; mp 186–
8-Methoxy-1-phenyl-3H-benzo[e]indole (IXc). 63%; mp 232–
233ꢀC (crystallization from heptane); 13C NMR (75 MHz, DMSO-
d6): d 137.1, 136.9, 134.7, 130.1, 130.3, 129.5, 129.2, 128.8, 127.7,
127.3, 127.4, 123.5, 119.6, 116.4, 116.5, 98.6, 54.6, 54.5, 37.3,
31.9 ppm; MS: m/z (%): 273 (M+, 100.0). Calcd for C19H15NO. C,
83.49; H, 5.53; N, 5.12. Found C, 83.33; H, 5.49; N, 5.02.
188ꢀC (crystallization from heptane); 1H NMR (300 MHz,
DMSO-d6): d 2.06 (s, 3H, CH3), 6.03 (s, 1H, H-1), 6.8 (s, 1H, H-
3), 7.51 (d, 1H, H-6, J6,5 = 8 Hz), 7.54–7.88 (m, 4H, Ar-H),
8.52ppm (d, 1H, H-5, J5,6 = 8 Hz); 13C NMR (75MHz, DMSO-
d6): d 136.9, 131.7, 129.0, 127.8, 127.3, 127.0, 126.5, 125.1,
124.2, 121.4, 111.7, 105.2, 21.4ppm. Calcd for C13H11N. C,
86.15; H, 6.12; N, 7.73. Found C, 86.10; H, 6.09; N, 7.56.
8,9-Dimethoxy-1-methyl-3H-benzo[e]indole (IXd).
66%; mp
172–174ꢀC (crystallization from heptane); 1H NMR (300 MHz,
DMSO-d6): d 2.31 (s, 3H, CH3), 3.83, 3.84 (s, s, 6H, 2OCH3), 6.96
(d, 1H, H-6, J6,7 = 8 Hz), 7.21 (s, 1H, H-2), 7.34 (d, 1H, H-4,
J4,5 = 8 Hz), 7.43 (d, 1H, H-6, J6,7 = 8 Hz), 7.61 (d, 1H, H-5,
J5,4 = 8 Hz), 10.2 ppm (s, 1H, NH); 13C NMR (75 MHz, DMSO-
d6): d 150.1, 134.8, 127.8, 127.7, 123.5, 123.1, 121.4, 118.7, 118.5,
117.854.1, 53.8, 33.6, 17.4 ppm. Calcd for C15H15NO2. C, 74.67;
H, 6.27; N, 5.81. Found C, 74.55; H, 6.14; N, 5.69.
2-Methoxy-2-methylpyrrolo[2,1-a]isoquinoline (VIIb). 78%;
mp 210–212ꢀC (crystallization from heptane); 1H NMR (300MHz,
DMSO-d6): d 2.08 (s, 3H, CH3), 3.91 (s, 3H, OCH3), 6.04 (s, 1H,
H-1), 6.9 (s, 1H, H-3), 7.01 (s, 1H, H-5), 7.25 (d, 1H, H-7,
J7,8 = 8 Hz), 7.45 (d, 1H, H-6, J6,5 = 8 Hz), 7.91 (d, 1H, H-8,
J8,7 = 8 Hz), 8.61ppm (d, 1H, H-5, J5,6 = 8 Hz); 13C NMR
(75 MHz, DMSO-d6): d 154.7, 137.8, 130.3, 125.1, 124.7, 120.6,
120.1, 120.0, 112.2, 108.7, 104.1, 56.4, 19.3 ppm; MS: m/z (%):
211 (M+, 100.0), 212 (M+ + 1, 20). Calcd for C14H13NO. C,
79.59; H, 6.20; N, 6.63. Found C, 79.33; H, 6.15; N, 6.49.
8-Methoxy-2-phenylpyrrolo[2,1-a]isoquinoline (VIIc). 56%;
mp 132–135ꢀC (crystallization from heptane); 13C NMR (75MHz,
DMSO-d6): d 162.4, 138.2, 136.4, 131.0, 130.6, 130.1, 130.0,
129.5, 127.8, 127.7, 127.6, 126.3, 125.9, 124.3, 123.9, 124.7,
120.3, 120.2, 110.1, 109.7, 108.2, 98.1, 56.3 ppm; MS: m/z (%):
173 (M+, 100.0), 274 (M+ + 1, 20). Calcd for C19H15NO. C,
83.49; H, 5.53; N, 5.12. Found C, 83.35; H, 5.38; N, 5.10.
8,9-Dimethoxy-1-phenyl-3H-benzo[e]indole (IXe). 56%; mp
210–212ꢀC (crystallization from heptane); 13C NMR (75MHz,
DMSO-d6): d 136.7, 136.4, 134.5, 130.4, 130.1, 129.2, 128.9,
128.6, 127.4, 127.1, 127.0, 123.7, 121.2, 119.3, 116.7, 116.3,
54.1, 54.6, 37.1, 31.5ppm; MS: m/z (%): 303 (M+, 100.0), 304
(M+ + 1, 15). Calcd for C20H17NO2. C, 79.19; H, 5.65; N, 4.62.
Found C, 79.10; H, 5.56; N, 4.55.
Acknowledgment. Dr. Ahmed El-Shafei, Polymer and Color
Chemistry Program, North Carolina State University, Raleigh,
USA, is greatly acknowledged for molecular modeling calculations.
8,9-Dimethoxy-2-methylpyrrolo[2,1-a]isoquinoline (VIId).
45%; mp 213–215ꢀC (crystallization from heptane); 1H NMR
(300 MHz, DMSO-d6): d 2.06 (s, 3H, CH3), 3.91 (s, 6H, 2OCH3),
6.84 (s, 1H, H-3), 6.91 (s, 1H, H-7), 7.10 (s, 1H, H-10), 7.4 (d,
1H, H-6, J6,5 = 8 Hz), 8.52 ppm (d, 1H, H-5, J5,6 = 8 Hz); 13C
NMR (75 MHz, DMSO-d6): d 154.5, 146.5, 137.1, 130.3, 125.4,
125.1, 121.2, 120.8, 120.5, 120.4, 112.6, 108.8, 104.9, 57.6, 57.1,
13.6ppm; MS: m/z (%): 241 (M+, 100.0). Calcd for C15H15NO2.
C, 74.67; H, 6.27; N, 5.81. Found C, 74.59; H, 6.21; N, 5.73.
8,9-Dimethoxy-2-phenylpyrrolo[2,1-a]isoquinoline (VIIe).
41%; mp 261–263ꢀC (crystallization from heptane); 13C NMR
(75 MHz, DMSO-d6): d 154.6, 146.4, 137.8, 136.7, 130.8, 130.7,
129.6, 129.4, 129.1, 128.3, 125.4, 120.6, 120.5, 119.3, 109.6, 57.3,
56.9 ppm; MS: m/z (%303 :( (M+, 100.0). Calcd for C20H17NO2. C,
79.19; H, 5.65; N, 4.62. Found C, 79.09; H, 5.55; N, 4.46.
REFERENCES AND NOTES
[1] Fadda, A. A.; Kost, A. N.; Sagitullin, R. S.; Gromove, S. P..
Reaktsionnaya Sposobnost Azinov SSSR, Novosibirsk, 1979, 69.
[2] Fadda, A. A.; Kost, A. N.; Sagitullin, R. S. Org Prep Proc Int
1981, 13, 203.
[3] Fadda, A. A.; Kost, A. N.; Sagitullin, R. S. Khim Geterotsikl
Soedin 1981, 125; Chem Abstr 1981, 95, 61643v.
[4] Kost, A. N.; Fadda, A. A.; Sagitullin, R. S.; Gromov, S. P.;
Petrunina, T. I.; Sharbatyan, P. A. Khim Geterotsikl Soedin No. 9,
1983, 1214; Chem Abstr 1983, 99, 212213r.
[5] Fadda, A. A.; Sagitullin, R. S. Indian J Chem Sect. B 1985, 24, 707.
[6] Fadda, A. A. Indian J Chem 1985, 24B, 970.
[7] Fadda, A. A.; El Morsy, S. S. Indian J Chem 1988, 27B, 361.
[8] Fadda, A. A.; Khalil A. M.; El-Habbal, M. M.; El Morsy, S. S.
Indian J Chem 1988, 27B, 266.
Rearrangement of IXa–e to benzoindole derivatives IXa–e.
These compounds were obtained according to the general procedure
for the synthesis of indole from indolizine.
[9] Fadda, A. A.; El-Habbal, M. M. Indian J Chem 1986, 25B, 194.
[10] Etman, H. A. Indian J Chem 1995, 34B, 285.
[11] Dainis, J. Aus J Chem 1972, 25, 1003.
1-Methyl-3H-benzo[e]indole (IXa).
81%; mp 181183ꢀC
1
[12] Vaimgahten, H. E.; Su, H. C. J Am Chem Soc 1954, 76, 596.
[13] (a) Mahadevan, I.; Rasmussen, M. J Heterocycl Chem 1992, 29,
359; (b) Niu, C.; Li, J.; Doyle, T. W.; Chen, S.-H. Tetrahedron 1998, 54, 6311.
[14] Hill, G. A.; Flosdort, E. W. Org Synth 1925, 5, 91.
[15] Fruer, R. J.; Earley, J. V.; Sternbach, L. H. J Org Chem 1967,
32, 3798.
(crystallization from heptane); H NMR (300 MHz, DMSO-d6): d
2.36 (s, 3H, CH3), 7.21 (s, 1H, H-2), 7.33 (d, 1H, H-4, J4,5 =8Hz),
7.61 (d, 1H, H-5, J5,4 = 8 Hz), 7.67 (m, 2H, H-7, H-8), 8.16 (t, 1H,
H-6, J6,5 = 8 Hz), 8.54 (t, 1H, H-9, J9,8 = 8 Hz), 10.2 ppm (s, 1H,
NH); 13C NMR (75 MHz, DMSO-d6): d 134.9, 130.6, 127.6, 127.5,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet