Preparation and Study of Tautomers Derived from 2-(2′-Pyridyl)indole and Related Compounds

Article abstract of DOI:10.1021/jo980134j

Methylation of 2-(2′-pyridyl)indole provides the corresponding N-methylated salt that undergoes deprotonation with mild base to provide the tautomeric (E)-1-methyl-2-(2′-indolenylidene)-l,2-dihydropyridine, whose geometry is established through a NOE expe

Full text of DOI:10.1021/jo980134j

J . Org. Chem. 1998, 63, 4055-4061
4055
P r ep a r a tion a n d Stu d y of Ta u tom er s Der ived fr om
2-(2′-P yr id yl)in d ole a n d Rela ted Com p ou n d s
Feiyue Wu, J on Hardesty, and Randolph P. Thummel*
Department of Chemistry, University of Houston, Houston, Texas 77204-5641
Received J anuary 26, 1998
Methylation of 2-(2′-pyridyl)indole provides the corresponding N-methylated salt that undergoes
deprotonation with mild base to provide the tautomeric (E)-1-methyl-2-(2′-indolenylidene)-1,2-
dihydropyridine, whose geometry is established through a NOE experiment. Bridging at the 3,3′-
positions leads to tautomers having the opposite stereochemistry. A benzo-fused analogue exhibits
similar behavior as does 2-(2′-quinolinyl)pyrrole. The importance of the connectivity to pyridine is
examined by considering three possible regioisomers, only two of which show tautomeric behavior.
The tautomers show strong solvatochromic dependence and good linear behavior. The indoles absorb
at shorter wavelengths and are strongly emitting while the tautomers show a strong bathochromic
shift and emit only weakly; the salts exhibit intermediate behavior. NMR properties are consistent
with contributions from a dipolar and uncharged resonance form while MO calculations indicate
that the indole is about 40 kcal/mol more stable than its tautomer.
In tr od u ction
to investigate the corresponding N-methylpyridinium
compounds that could lead to methylated analogues of 2
incapable of simple tautomeric reversion. This paper will
report the results of that study.
The photophysical behavior of a number of heteroaro-
matic systems is dominated by changes in the acid and
base character of the excited state. One manifestation
of this behavior is photoinduced proton transfer, and we
have recently been studying these effects as they apply
to the 2-(2′-pyridyl)indole molecule (1).1 Intramolecular
proton transfer can be assisted by alcohol solvents, and
the involvement of indole tautomers such as 2 became
of interest. This ring system appears to be as yet
unreported, although related species involving 4′-pyridyl
substituents2 or 3-substituted indoles3 are known.
Molecules such as 1 are of particular interest because
of the complementary juxtaposition of the pyridine and
pyrrole rings. Pyridine is π-deficient but exhibits Lewis
basicity because of its available lone-pair electrons. As
such, it is a good H-bond acceptor. Pyrrole or indole, on
the other hand, is π-excessive and exhibits increased
reactivity toward electrophiles. It is comparably nonbasic
and a good H-bond donor. The juxtaposition of these two
nuclei in a 1,4-relationship is particularly interesting in
that the two centers can potentially be interacting. To
inhibit the tautomerization between 1 and 2, we chose
Resu lts a n d Discu ssion
Treatment of 1 with excess methyl iodide in acetonitrile
leads to formation of the corresponding pyridinium salt
3 in 73% yield. When 3 is treated with ammonium
hydroxide, a red solid is obtained in 53% yield, which
1
showed an H NMR similar to the starting salt but with
a general upfield shift of all resonances. In accordance
with the appearance of 13 signals in the 13C NMR, the
material was identified as the indole tautomer 4. Pos-
sible ambiguity with respect to stereochemistry about the
double bond was resolved by an NOE experiment in
which irradiation of the N-methyl peak at 4.56 ppm
showed an enhancement of H3 at 7.23 ppm, which would
only be possible for the trans isomer. This result implies
that deprotonation occurs from the transoid conformer
of 3 in which the N-H is sterically more accessible to
the base.
The tautomeric analogue of 4 was prepared from the
1-methyl-1-phenylhydrazone of 2-acetylpyridine (5) by a
straightforward application of the Fisher indole synthe-
sis.4 If methyl group migration were possible, one might
imagine that 4 could revert back to the indole form and
(1) (a) Herbich, J .; Hung, C.-Y.; Thummel, R. P.; Waluk, J . J . Am.
Chem. Soc. 1996, 118, 3508. (b) Herbich, J .; Waluk, J .; Thummel, R.
P.; Hung, C.-Y. J . Photochem. Photobiol. A 1994, 80, 157. (c) Herbich,
J .; Rettig, W.; Thummel, R. P.; Waluk, J . Chem. Phys. Lett. 1992, 195,
556.
(2) (a) Stupnikova, T. V.; Zemskii, B. P.; Vysotskii, Yu. B.; Sagitullin,
R. S.; Lopatinskaya, Kh. Ya. Chem. Heterocycl. Compd. (Engl. Transl.)
1980, 7, 743. (b) Sheinkamn, A. K.; Zemskii, B. P.; Stupnikova, T. V.;
Vysotskii, Yu. B.; Kost, A. N.Chem. Heterocycl. Compd. (Engl. Transl.)
1978, 11, 1199. (c) Zemskii, B. P.; Sheinkamn, A. K. Chem. Heterocycl.
Compd. (Engl. Transl.) 1981, 12, 1205. (d) Zemskii, B. P.; Vysotskii,
Yu. B.; Stupnikova, T. V.; Kost, A. N.; Sheinkman, A. K. Ukr. Chem.
J . (Engl. Transl.) 1980, 46, 80. (e) Stupnikova, T. V.; Rybenko, L. A.;
Kost, A. N.; Sagitullin, R. S.; Kolodin, A. I.; Marshtupa, V. P. Chem.
Heterocycl. Compd. (Engl. Transl.) 1980, 6, 585.
(3) (a) Klyuev, N. A.; Sheinkman, A. K.; Khmel’nitskii, R. A.;
Mal’tseva, G. A.; Kal’nitskii, N. R. Russ. J . Org. Chem. (Engl. Transl.)
1977, 13, 991. (b) Zemskii, B. P.; Stupnikova, T. V.; Sheinkman, A.
K.; Vysotskii, Yu. B. Russ. J . Org. Chem. (Engl. Transl.) 1979, 15, 2200.
(c) Stupnikova, T. V.; Petrenko, V. V. Chem. Heterocycl. Compd. (Engl.
Transl.) 1983, 4, 460.
(4) Robinson, B. The Fisher Indole Synthesis; J ohn Wiley and Sons:
Chichester, 1982.
S0022-3263(98)00134-0 CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/22/1998

4056 J . Org. Chem., Vol. 63, No. 12, 1998
Wu et al.
thus provide the tautomeric structure 6. No evidence for
such tautomeric reversion has been observed under
thermal or photochemical conditions.
Methylation of 11 provided the quinolinium salt 12,
which upon deprotonation gave the indole tautomer 13
in 48% yield.
It became of interest to see if the same tautomerism
would be evidenced by pyridylpyrrole derivatives. There
is a brief report that indicates that the N-methylpyri-
dinium salt 14 of the parent system, 2-(2′-pyridyl)pyrrole,
deprotonates to form the corresponding tautomer 15.9
The Russian workers further indicate that heating this
tautomer promotes methyl migration to provide the
N-methylpyrrole derivative 16. This migration would
require the cis-geometry as they indicate for 15, which
is, however, not in accord with what we have observed
for 4. The more favorable proton abstraction from the
less hindered transoid conformation of 14 should lead to
the trans isomer 17 for which methyl migration would
be even more unlikely.
To better evaluate the factors influencing formation of
the trans isomer as well as the propensity for tautomeric
reversion, 3-methyl-2-(2′-pyridyl)indole (7a ) was next
prepared by treatment of the phenylhydrazone of 2-pro-
pionylpyridine with PPA.5 Steric interaction between the
methyl groups of the corresponding N-methylpyridinium
salt (8a ) should favor the cisoid conformation of this
species. Thus, deprotonation of 8a led to a 51% yield of
9a having the opposite stereochemistry from 4 as deter-
mined by the upfield shift of H3′ as compared with the
same resonance for 4 where this proton is deshielded by
the lone pair electrons of the indolylidene nitrogen (see
Table 3).
Bridging the 3,3′-positions of 2-(2′-pyridyl)indole can
accomplish the same geometric restriction. We have
previously reported the preparation of 3,3′-polymethyl-
ene-bridged indoles 7b,c,6 which can be methylated to
afford the salts 8b,c. Deprotonation of these salts then
provides the indole tautomers 9b,c. Additional conjuga-
tion between the pyridine and indole, which results from
incorporating an unsaturated bridge, does not alter the
course of the reaction. The dimethylene-bridged indole
7b may be dehydrogenated by refluxing with 10% Pd/C
in nitrobenzene. The resulting pyridocarbazole 7d 7 may
be methylated to 8d , and deprotonation with ammonium
hydroxide provides a 79% yield of the fully conjugated
indole tautomer 9d .
The described synthesis of the 2-(2′-pyridyl)pyrrole
precursor to 14 appeared quite tedious.10 Instead, we
prepared the analogous 2-(2′-quinolinyl)pyrrole (20a ) by
the direct Friedla¨nder condensation of 2-aminobenzal-
dehyde with 2-acetylpyrrole.11 Subsequent methylation
provided the salt 21, which underwent deprotonation to
the pyrrole tautomer 23. The question of stereochemistry
in 23 was established by a NOE experiment in which
irradiation of the N-methyl group showed enhancement
of both H8 and H3′. Thus, we are inclined to believe that
the deprotonation product from 14 was, in fact, 17 and
that thermal isomerization to 16 did not occur. We have
not observed thermal or photochemical methyl migration
even in systems such as 9a -d , which are constrained to
a cis conformation.
(6) Thummel, R. P.; Hegde, V. J . Org. Chem. 1989, 54, 1720.
(7) Mulka, M.; Manske, R. H. F. Can. J . Chem. 1952, 30, 711.
(8) J ahng, Y.; Thummel, R. P.; Bott, S. Inorg. Chem. 1997, 36, 3133.
(9) Stupnikova, T. V.; Rybenko, L. A.; Kolodin, A. I.; Marshtupa, V.
P. Khim. Geterosik. Soedin. 1981, 11, 1568.
(10) Savoia, D.; Concialini, V.; Roffia, S.; Tarai, L. J . Org. Chem.
1991, 56, 1822.
A benzo-fused analogue of 7b was prepared by Fischer
indolization of 1,2,3,4-tetrahydroacridin-4-one,8 affording
12,13-dihydro-5H-indolo[3,2-c]acridine (11) in 70% yield.
(11) (a) Ohkura, K.; Seki, K.; Terashima, M.; Kanaoka, Y. Hetero-
cycles 1990, 30, 957. (b) Matoba, K.; Shibata, M.; Yamazaki, T. Chem.
Pharm. Bull. 1982, 30, 1718.
(5) Bradsher, C. K.; Litzinger, E. F., J r. J . Org. Chem. 1964, 29,
3584.

Tautomers Derived from 2-(2′-Pyridyl)indole
J . Org. Chem., Vol. 63, No. 12, 1998 4057
An analogous Friedla¨nder condensation using 2-ami-
nonicotinaldehyde provided the 2-(2′-[1,8]naphthyridyl)
derivative 20b, which preferentially methylated at the
8-position, providing the salt 22. Attempted deprotona-
tion of this salt led to unstable material that could not
be characterized.
interest since they exhibit a progressive bathochromic
shift of the longest wavelength band (Figure 1). This
shift can be associated with a decrease in the π-π*
HOMO-LUMO gap reflected by an increase in the total
energy of the system. More subtle structural influences
on the stability of the indole tautomers are reflected by
their absorption maxima as recorded in Table 1. The two
methyl groups in 9a cause a slight twisting about the
2,2′-bond, diminishing delocalization and shifting the
band to higher energy relative to 4. The dimethylene
bridge in 9b forces coplanarity and has the opposite
effect. Dehydrogenation of the bridge considerably in-
creases delocalization and flattening of the system to
cause a 30 nm bathochromic shift for 9d , while ap-
proximately the same shift is observed for 13, which is a
benzo-fused analogue of 9b.
A tetrahydro derivative of 7d could be prepared from
the PPA-promoted Fisher indolization of the 8-quinoline-
hydrazone of cyclohexanone, thus affording 25. The
aromatic nucleus of 25 is related to 2-(2′-pyridyl)pyrrole
in the same way that 1,10-phenanthroline is related to
2,2′-bipyridine. Methylation provided the salt 26, and
deprotonation led smoothly to the tautomer 27.
The indole tautomers exhibit solvatochromic behavior.
In less polar solvents, the uncharged form of the tautomer
is favored. This species exhibits a lower energy or longer
wavelength electronic absorption. For 9b in hexane, this
value is about 446 nm. In more polar solvents, the
dipolar resonance form assumes greater importance and
the absorption maximum shifts to higher energy or
shorter wavelength, around 408 nm for 9b in DMSO.
Plotting the absorption maxima vs the polarity index of
the solvent shows approximately linear behavior (Figure
2).
A unique and important property of the indole nucleus
is its ability to fluoresce. Table 2 lists the emission
The position of substitution on the pyridine ring of 1
is important in determining the tautomeric nature of the
corresponding pyridyl indole. Previous workers have
examined the 4-pyridyl and 3-pyridyl isomers 28 and 31
and observed that the former tautomerizes readily2 while
the latter does not. We repeated their work to have
information on the series of three isomers, 1, 28, and 31.
Fisher indolization of the phenylhydrazones derived from
4- and 3-acetylpyridine provided the pyridylindoles 28
and 31, which could be methylated with methyl iodide
to the corresponding pyridinium salts 29 and 32. Depro-
tonation of 29 proceeded smoothly to afford the tautomer
30, but similar reaction of 32 could only be accomplished
under more severe conditions and the dipolar product 33
was stable only for minutes in DMSO-d6 where its NMR
spectrum could be determined.
The electronic absorption spectra of the pyridylindoles,
their pyridinium salts, and the indole tautomers are of
F igu r e 1. Electronic absorption spectra for 1, 3, and 4 (8 ×
10-5 M in CH3CN): 1 (s), 3 (‚‚‚), 4 (- -).

4058 J . Org. Chem., Vol. 63, No. 12, 1998
Wu et al.
Ta ble 1. Lon g-Wa velen gth Electr on ic Absor p tion
Ma xim a for P yr id ylin d ole Der iva tivesa
electrons on the indole nitrogen. The indole tautomers
are expected to evidence considerable double-bond char-
acter for the 2-2′ bond, which connects the two cyclic
portions of the molecule. One can write a dipolar
resonance form 34 for this species, which would decrease
indole
λmax
salt
λmax
tautomer
λmax
1
7a
7b
7c
7d
11
20a
20b
25
28
31
321 (4.36)
328 (4.24)
337 (4.36)
328 (4.39)
339 (3.67)
377 (4.38) 12
350 (4.36) 21
364 (4.37) 22
350 (3.57) 26
321 (4.42) 29
311 (4.36) 32
3
364 (4.10)
360 (3.82)
389 (4.39)
374 (4.10)
383 (3.98)
432 (4.51)
401 (4.32)
429 (4.32)
408 (4.01)
381 (4.44)
324 (4.29)
4
9a
9b
9c
9d
13
23
411 (3.96)
389 (3.65)
414 (4.35)
410 (3.94)
444 (3.76)
450 (4.39)
444 (4.28)
8a
8b
8c
8d
27
30
486 (3.93)
432 (4.21)
this double bond character while accumulating positive
charge on the pyridinium ring and negative charge on
the indole. It is expected that factors that tend to force
the two rings out of coplanarity would favor the contribu-
tion of this resonance form, and such an increased
contribution might be reflected in the chemical shifts of
the protons on the respective rings. In comparing the
tautomers 4 and 9a , this effect becomes evident in that
the pyridine ring protons, H4′-H6′, are shifted downfield
0.06-0.10 ppm while the indole protons, H4-H7, are
shifted upfield 0.13-0.18 ppm. Furthermore, as we
proceed along the series 9b, 9c, 9a , we expect the
dihedral angle between the rings to increase and we do
observe a downfield trend for all four protons in the
pyridine ring along this series. A corresponding upfield
shift is not as clearly evidenced for the indole protons
possibly due to the greater localization of the negative
charge on the pyrrole moiety.
a
8 × 10-5 M in CH3CN; λmax in nm and log ꢀ in parentheses.
F igu r e 2. Solvatochromic behavior for indole tautomer 9b (8
× 10-5 M).
Molecular orbital calculations12 were carried out at the
Hartree-Fock level using the 3-21G basis set13 on the
isomeric structures 4 and 6 to assess the importance of
resonance stabilization in 6 versus the planarity and
delocalization exhibited by 4. The difference in total
energies between these two isomers was 39.84 kcal/mol,
favoring the pyridylindole. The cisoid form of 4 was
found to be more stable than the transoid isomer by about
2.96 kcal/mol, indicating that the deprotonation is kineti-
cally controlled. This difference is comparable to the
difference in energies between the two planar conformers
of 6 where the transoid species is 4.26 kcal/mol higher
in energy.
Ta ble 2. Em ission Ma xim a for P yr id ylin d ole
Der iva tivesa
indoleb
λmax
salt
λmax
1
7a
7b
7c
7d
11
20a
20b
25
28
31
376 (676)c
399 (247)
404 (711)
389 (85)
423 (110)
434 (449)
424 (371)
452 (267)
422 (10)
384d
3
8a
8b
8c
8d
12
21
22
26
29
32
506 (s)e
419 (m)
543 (w)
541 (m)
551 (m)
541 (s)
447 (m)
515 (m)
504 (s)
508 (w)
424 (w)
385 (722)
a
b
8 × 10-5 M in CH3CN. Excited at long-wavelength band
where absorbance ) 1.00. c λ in nm and relative intensity in
Exp er im en ta l Section
d
parentheses. Relative intensity more than 1000. e λ in nm; due
Nuclear magnetic resonance spectra were obtained at 300
MHz for 1H and 75 MHz for 13C. Melting points were
measured with a capillary melting point apparatus and are
not corrected. Elemental analyses were performed by National
Chemical Consulting, Inc., Tenafly, NJ . The indole tautomers
were not sufficiently stable to allow combustion analysis; their
NMR (excepting 13C for 9a ,c) spectra are contained in the
Supporting Information.
to wide variation, relative intensities are qualitative.
maxima for the indoles and their salts. The emission
intensity is strongest for the parent indoles, less for the
salts, and very weak for the tautomers. Of the indoles,
the most intense emissions are for the 2-pyridylindoles,
1, 28, and 31. The weakest emission is for 25, which
could also be viewed as a pyrroloquinoline derivative.
Table 3 presents a comparison of the1H NMR chemical
shift data for indole tautomers 4 and 9a -d . Two
interesting features are in evidence. The H3′ proton of 4
is shifted downfield due to deshielding by the lone pair
The pyridylindoles 1, 6, and 7b,c,1a,6 4-oxo-1,2,3,4-tetrahy-
droacridine (10),8 and 8-hydrazinoquinoline (24)14 were pre-
pared according to previously described procedures. The 2-(2′-
pyridyl)-3-methylindole (7a ) was prepared according to the
method of Bradsher and Litzinger,5 the 2-aminobenzaldehyde
(18a ) was prepared according to the method of Opie and
Smith,15 and the 2-aminonicotinaldehyde (18b) was prepared
according to the method of Majewicz and Caluwe.16
(12) Gaussian 94, Rev. B.1: Frisch, M. J .; Trucks, G. W.; Schlegel,
H. B.; Gill, P. M. W.; J ohnson, B. G.; Robb, M. A.; Cheeseman, J . R.;
Kieth, T.; Peterson, G. A.; Montgomery, J . A.; Raghavachari, K.; Al-
Laham, M. A.; Zakrzewski, V. G.; Ortiz, J . V.; Foresman, J . B.;
Cioslowski, J .; Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.;
Peng, C. Y.; Ayala, P. Y.; Chen, W.; Wong, M. W.; Andres, J . L.;
Replogle, E. S.; Comperts, R.; Martin, R. L.; Fox, D. J .; Binkley, J . S.;
Defrees, D. J .; Baker, J .; Stewart, J . P.; Head-Gordon, M.; Gonzalez,
C.; Pople, J . A. Gaussian, Inc., Pittsburgh, PA, 1995.
(13) Binkley, J . S.; Pople, J . A.; Hehre, W. J . J . Am. Chem. Soc. 1980,
102, 2, 939.
(14) Hegde, V.; Hung, C.-Y.; Madhukar, P.; Cunningham, R.;
Ho¨pfner, T.; Thummel, R. P. J . Am. Chem. Soc. 1993, 115, 872.
(15) Opie, J . W.; Smith, L. I. Organic Syntheses; Wiley: New York,
1955; Collect. Vol. III, p 56.

Tautomers Derived from 2-(2′-Pyridyl)indole
J . Org. Chem., Vol. 63, No. 12, 1998 4059
Ta ble 3. 1H NMR Ch em ica l Sh ift Da ta for In d ole Ta u tom er sa
compd
H3′
H4′
H5′
H6′
H3
H4
H5
H6
H7
NCH3
bridge
4,b R1 ) H3′, R2 ) H3
9a , R1 ) H3′, R2 ) CH3
9b, R1, R2 ) CH2CH2
9c, R1, R2 ) (CH2)3
8.52
8.00
8.22
8.28
7.90
8.23
8.98
7.59
7.66
7.19
7.57
7.77
8.66
8.76
8.21
8.64
8.98
7.23
7.53
7.38
7.36
7.42
7.76
6.81
6.68
6.65
6.69
7.06
6.99
6.81
6.82
6.85
7.32
7.41
7.28
7.31
7.33
7.47
4.56
4.52
4.79
4.59
5.39
2.43 (CH3)
3.03, 2.97
2.80, 2.58, 2.21
8.53, 8.21
9d , R1, R2 ) CHdCH
a
b
Recorded in DMSO-d6 at 25 °C. Chemical shifts reported in ppm downfield from Me4Si. Reverse stereochemistry about NCdCN.
1-Meth yl-2-(2′-in d olyl)p yr id in iu m Iod id e (3). A mix-
ture of 2-(2′-pyridyl)indole (1, 4.0 g, 20.6 mmol) and methyl
iodide (8.8 g, 61.8 mmol) in acetonitrile (50 mL) was refluxed
for 19 h. After cooling, a precipitate was collected and dried
to afford 3 as a brown solid (5.1 g, 73%), which was recrystal-
lized from water: mp 227-9 °C; 1H NMR (DMSO-d6) δ 12.13
(s, 1H, NH), 9.10 (d, 1H, J ) 5.7 Hz, H6), 8.63 (t, 1H, J ) 7.7
Hz, H4), 8.31 (d, 1H, J ) 8.1 Hz, H3), 8.04 (t, 1H, J ) 6.6 Hz,
H5), 7.74 (d, 1H, J ) 8.1 Hz, H4′), 7.56 (d, 1H, J ) 8.4 Hz, H7′),
7.38 (s, 1H, H3′), 7.33 (t, 1H, J ) 7.7 Hz, H6′), 7.16 (t, 1H, J )
7.5 Hz, H5′), 4.47 (s, 3H, CH3); 13C NMR (DMSO-d6) δ 147.1,
147.0, 144.5, 137.7, 128.7, 127.3, 126.6, 125.3, 124.9, 121.7,
120.6, 112.2, 110.0, 47.9. Anal. Calcd for C14H13N2I: C, 50.00;
H, 3.87; N, 8.33. Found: C, 50.12; H, 3.83; N, 8.20.
H4), 8.24 (d, 1H, J ) 7.8 Hz, H3), 8.19 (t, 1H, J ) 6.9 Hz, H5),
7.69 (d, 1H, J ) 8.1 Hz, H4′), 7.50 (d, 1H, J ) 8.1 Hz, H7′ ),
7.30 (t, 1H, J ) 7.7 Hz, H6′ ), 7.14 (t, 1H, J ) 7.4 Hz, H5′), 4.23
(s, 3H, N-CH3), 2.31 (s, 3H, C-CH3); 13C NMR (DMSO-d6) δ
147.4, 147.3, 145.0, 136.9, 131.1, 127.5, 126.7, 124.3, 123.8,
119.9, 119.8, 115.2, 112.0, 47.0, 9.2. Anal. Calcd for C14H13N2I‚
0.25H2O: C, 50.77; H, 4.37; N, 7.90. Found: C, 50.79; H, 4.09;
N, 7.53.
1-Meth yl-3,3′-d im eth ylen e-2-(2′-in d olyl)p yr id in iu m Io-
d id e (8b). Following the procedure described for 3, 3,3′-
dimethylene-2-(2′-pyridyl)indole (7b, 1.51 g, 6.9 mmol) was
treated with methyl iodide (2.94 g, 20.7 mmol) for 20 h to afford
8b as a brown solid (1.99 g, 80%): mp 280-2 °C; 1H NMR
(DMSO-d6) δ 11.61 (s, 1H, NH), 8.67 (d, 1H, J ) 6.0 Hz, H6),
8.34 (d, 1H, J ) 7.5 Hz, H4), 7.75-7.69 (overlapping, 2H, H5
and H4′), 7.62 (d, 1H, J ) 8.4 Hz, H7′), 7.36 (t, 1H, J ) 7.7 Hz,
H6′), 7.16 (t, 1H, J ) 7.5 Hz, H5′), 4.56 (s, 3H, N-CH3), 3.16 (t,
2H, J ) 6.6 Hz, 3-CH2), 3.06 (t, 2H, J ) 6.9 Hz, 3′-CH2); 13C
NMR (DMSO-d6) δ 144.1, 143.6, 142.0, 139.8, 137.7, 126.4,
126.2, 124.3, 124.1, 123.0, 120.8, 120.5, 113.0, 47.2, 28.9, 18.2.
1-Meth yl-2-(2′-in dolen yliden e)-1,2-dih ydr opyr idin e (4).
A mixture of 1-methyl-2-(2′-indolyl)pyridinium iodide (3, 1.0
g, 3.0 mmol) and sodium acetate (2.0 g) in water (40 mL) was
heated to dissolve completely. After the mixture was cooled
to room temperature, ammonium hydroxide (10 mL) was
added, and the solution was stirred for 10 min. The solution
was then extracted with CH2Cl2 (3 × 50 mL). The organic
layer was dried over anhydrous Na2CO3, and the solvent was
evaporated to afford 4 as a red solid (0.33 g, 53%): mp 56 °C
Anal. Calcd for
C16H15N2I: C, 53.04; H, 4.14; N, 7.73.
Found: C, 53.05; H, 4.38; N, 7.63.
1-Meth yl-3,3′-tr im eth ylen e-2-(2′-in dolyl)p yr id in iu m Io-
d id e (8c). Following the procedure described for 3, 3,3′-
trimethylene-2-(2′-pyridyl)indole (7c, 0.20 g, 0.85 mmol) was
treated with methyl iodide (2.0 g, 14 mmol) for 20 h to afford
8c as a brown solid (0.15 g, 49%): mp 245-7 °C; 1H NMR
(DMSO-d6) δ 11.67 (s, 1H, NH), 9.00 (d, 1H, J ) 5.7 Hz, H6),
8.56 (d, 1H, J ) 7.8 Hz, H4), 7.98 (t, 1H, J ) 6.9 Hz, H5), 7.77
(d, 1H, J ) 7.8 Hz, H4′), 7.56 (d, 1H, J ) 8.4 Hz, H7′), 7.33 (t,
1H, J ) 7.7 Hz, H6′), 7.16 (t, 1H, J ) 7.4 Hz, H5′), 4.38 (s, 3H,
N-CH3), 2.81 (t, 2H), 2.64 (t, 2H), 2.31 (quintet, 2H); 13C NMR
(DMSO-d6) δ 147.7, 145.4, 145.0, 144.8, 142.5, 127.7, 126.0,
124.9, 123.3, 123.0, 120.0, 119.5, 112.4, 47.6, 33.2, 31.3, 19.3.
1
dec; H NMR (DMSO-d6) δ 8.66 (d, 1H, J ) 6.0 Hz, H6), 8.52
(d, 1H, J ) 8.4 Hz, H3), 8.22 (t, 1H, J ) 7.7 Hz, H4), 7.59 (t,
1H, J ) 6.5 Hz, H5), 7.53 (d, 1H, J ) 7.8 Hz, H4′), 7.41 (d, 1H,
J ) 8.1 Hz, H7′), 7.23 (s, 1H, H3′), 6.99 (t, 1H, J ) 7.5 Hz, H6′),
6.81 (t, 1H, J ) 7.4 Hz, H5′), 4.56 (s, 3H, CH3); 13C NMR
(DMSO-d6) δ 151.1, 145.5, 142.0, 133.7, 129.8, 128.1, 121.9,
121.13, 121.06, 118.3, 116.6, 108.3, 108.2, 47.8; MS m/z 208
(M+), 193 (M - 15).
11H-P yr id o[2,3-a ]ca r ba zole (7d ). A mixture of 10,11-
dihydro-5H-pyrido[2,3-a]carbazole (7b, 0.78 g, 3.5 mmol) and
10% Pd/C (0.10 g) in nitrobenzene (6 mL) was heated to 170-5
°C for 4 h. An additional 10% Pd/C (0.10 g) and nitrobenzene
(3 mL) were added and the mixture was stirred overnight at
170-5 °C. The reaction mixture was cooled to room temper-
ature and filtered. The filtered solid was washed with CH2-
Cl2 (5 × 5 mL), and the filtrate and washings were combined.
The solvent was evaporated, and the residue was chromato-
graphed on alumina (24 g), eluting with benzene and then
EtOAc. Nitrobenzene and aniline were eluted with the
benzene fraction. A slightly brown solid (0.59 g, 77%), obtained
from the EtOAc fraction, was recrystallized from EtOH to
afford 7d : mp 164-5 °C (lit.7 mp 172-3 °C); 1H NMR (CDCl3)
δ 10.93-10.77 (bs, 1H, NH), 8.96 (dd, 1H, H2), 8.37 (d, 1H, J
) 8.1 Hz, H4), 8.25 (d, 1H, J ) 8.4 Hz, H6), 8.18 (d, 1H, J )
7.8 Hz, H7), 7.62 (d, 1H, J ) 8.4 Hz, H10), 7.54-7.48 (overlap-
ping, 2H, H3 and H5), 7.46 (t, 1H, J ) 7.8 Hz, H9), 7.33 (t, 1H,
J ) 7.4 Hz, H8).
Anal. Calcd for
C17H17N2I: C, 54.26; H, 4.52; N, 7.45.
Found: C, 54.05; H, 4.48; N, 7.85.
1-Meth yl-11H-p yr id o[2,3-a ]ca r ba zoliu m Iod id e (8d ).
Following the procedure described for 3, 11H-pyrido[2,3-a]-
carbazole (7d , 0.44 g, 2 mmol) was treated with methyl iodide
(0.85 g, 6 mmol) for 20 h to afford 8d as a brown-yellow solid
1
(0.51 g, 71%): mp 254-6 °C; H NMR (DMSO-d6) δ 12.33 (s,
1H, NH), 9.37 (d, 1H, J ) 5.7 Hz, H2), 9.32 (d, 1H, J ) 8.1 Hz,
H4), 8.83 (d, 1H, J ) 8.7 Hz, H6), 8.45 (d, 1H, J ) 7.8 Hz, H7),
8.13 (overlapping, 2H, H5 and H3), 7.92 (d, 1H, J ) 8.1 Hz,
H
10), 7.67 (t, 1H, J ) 7.6 Hz, H9), 7.43 (t, 1H, J ) 7.6 Hz, H8),
5.08 (s, 3H, N-CH3); 13C NMR (DMSO-d6) δ 147.7, 147.6,
146.2, 140.5, 129.1, 128.9, 128.1, 126.8, 126.0, 123.4, 120.9,
120.8, 120.5, 120.1, 112.8, 48.9. Anal. Calcd for C16H13N2I:
C, 53.33; H, 3.61; N, 7.78. Found: C, 53.34; H, 3.49; N, 7.40.
1-Meth yl-2-[2′-(3′-m eth ylin d olen ylid en e)]-1,2-d ih yd r o-
p yr id in e (9a ). To a solution of 1-methyl-2-[2′-(3′-methylin-
dolyl)]pyridinium iodide (8a , 0.35 g, 1.0 mmol) in water (10
mL) was added cold 5% KOH solution (40 mL), and the
mixture was stirred for 10 min. The solution was extracted
with CH2Cl2 (3 × 50 mL), and the organic layer was dried over
anhydrous Na2CO3. The solvent was evaporated to afford a
red solid 9a (0.11 g, 51%): mp 55 °C dec; 1H NMR (DMSO-d6)
δ 8.76 (d, 1H, J ) 6.3 Hz, H6), 8.28 (t, 1H, J ) 7.7 Hz, H4),
1-Met h yl-2-[2′-(3′-m et h ylin d olyl)]p yr id in iu m Iod id e
(8a ). Following the procedure described for 3, 2-(2′-pyridyl)-
3-methylindole (7a , 2.4 g, 11.5 mmol) was treated with methyl
iodide (4.9 g, 34.5 mmol) for 22 h to afford 8a as a brown solid
1
(1.29 g, 32%): mp 207-9 °C; H NMR (DMSO-d6) δ 11.50 (s,
1H, NH), 9.21 (d, 1H, J ) 6.0 Hz, H6), 8.67 (t, 1H, J ) 7.8 Hz,
(16) Caluwe, P.; Majewicz, T. J . Org. Chem. 1979, 44, 531.

4060 J . Org. Chem., Vol. 63, No. 12, 1998
Wu et al.
8.00 (d, 1H, J ) 8.1 Hz, H3), 7.66 (t, 1H, J ) 6.6 Hz, H5), 7.38
(d, 1H, J ) 8.1 Hz, H4′), 7.28 (d, 1H, J ) 8.1 Hz, H7′), 6.81 (t,
1H, J ) 7.4 Hz, H6′), 6.68 (t, 1H, J ) 7.2 Hz, H5′), 4.52 (s, 3H,
NCH3), 2.43 (s, 3H, CCH3); MS m/z 222 (M+), 208 (M - 14).
1-Meth yl-3,3′-d im eth ylen e-2-(2′-in d olen ylid en e)-1,2-d i-
h yd r op yr id in e (9b). Following the procedure described for
4, 1-methyl-3,3′-dimethylene-2-(2′-indolyl)pyridinium iodide
(8b, 0.30 g, 0.8 mmol) was treated with ammonium hydroxide
(10 mL) to afford 9b as a red solid (0.12 g, 62%): mp 45 °C
1H, J ) 7.7 Hz, H8), 7.89-7.83 (overlapping, 2H, H1 and H9),
7.66 (d, 1H, J ) 8.4 Hz, H4), 7.46 (t, 1H, J ) 7.7 Hz, H3), 7.22
(t, 1H, J ) 7.4 Hz, H2), 4.68 (s, 3H, N-CH3), 3.26-3.18
(overlapping, 4H, H12 and H13); 13C NMR (DMSO-d6) δ 147.5,
140.8, 140.6, 138.7, 133.8, 133.5, 131.5, 129.0, 128.6, 128.0,
126.8, 125.2, 124.5, 121.3, 121.2, 118.9, 113.2, 41.9, 28.8, 18.7.
Anal. Calcd for C20H17N2I: C, 58.25; H, 4.13; N, 6.80.
Found: C, 58.59; H, 4.04; N, 7.07.
1-Meth yl-3,3′-d im eth ylen e-2-(2′-in d olen ylid en e)-1,2-d i-
h yd r oqu in olin e (13). Following the procedure described for
4, 6-methyl-12,13-dihydro-5H-indolo[3,2-c]acridinium iodide
(12, 89 mg, 0.22 mmol) was treated with ammonium hydroxide
(10 mL) to afford 13 as a red solid (29 mg, 48%): mp 72-4 °C
1
dec; H NMR (DMSO-d6) δ 8.21 (d, 1H, J ) 6.3 Hz, H6), 7.90
(d, 1H, J ) 7.5 Hz, H4), 7.36 (d, 1H, J ) 8.1 Hz, H4′), 7.31 (d,
1H, J ) 8.1 Hz, H7′), 7.19 (t, 1H, J ) 6.9 Hz, H5), 6.82 (t, 1H,
J ) 7.4 Hz, H6′), 6.65 (t, 1H, J ) 7.4 Hz, H5′), 4.79 (s, 3H,
NCH3), 3.03 (t, 2H, J ) 6.6 Hz, 3-CH2), 2.97 (t, 2H, J ) 6.9
Hz, 3′-CH2); 13C NMR (DMSO-d6) δ 151.0, 148.7, 142.0, 138.4,
137.1, 135.5, 126.9, 122.8, 121.3, 119.6, 119.4, 118.4, 116.3,
47.0, 30.5, 19.8; MS m/z 234 (M+).
1
dec; H NMR (DMSO-d6) δ 8.28 (s, 1H, H4), 8.10 (d, 1H, J )
8.7 Hz, H8), 7.91 (d, 1H, J ) 7.5 Hz, H5), 7.83 (t, 1H, J ) 8.0
Hz, H7), 7.60 (t, 1H, J ) 7.5 Hz, H6), 7.41 (d, 1H, J ) 8.1 Hz,
H4′), 7.33 (d, 1H, J ) 8.7 Hz, H7′), 6.91 (t, 1H, J ) 7.4 Hz, H6′),
6.68 (t, 1H, J ) 7.4 Hz, H5′), 5.22 (s, 3H, N-CH3), 3.13-3.05
(overlapping, 4H, CH2CH2); 13C NMR (DMSO-d6) δ 154.2,
151.0, 139.7, 136.1, 135.5, 135.3, 132.2, 131.4, 128.1, 127.2,
126.0, 125.7, 125.4, 120.8, 120.1, 118.5, 119.4, 116.5, 40.4, 31.5,
20.7; MS m/z 284 (M+), 268 (M - 16).
1-Met h yl-3,3′-t r im et h ylen e-2-(2′-in d olen ylid en e)-1,2-
d ih yd r op yr id in e (9c). Following the procedure described for
4, 1-methyl-3,3′-trimethylene-2-(2′-indolyl)pyridinium iodide
(8c, 75 mg, 0.2 mmol) was treated with ammonium hydroxide
(10 mL) to afford 9c as a red solid (31 mg, 63%): mp 43 °C
1
dec; H NMR (DMSO-d6) δ 8.64 (d, 1H, J ) 6.0 Hz, H6), 8.23
2-(2′-P yr r olyl)qu in olin e (20a ). A mixture of 2-aminoben-
zaldehyde (18a , 1.21 g, 10.0 mmol) and 2-acetylpyrrole (1.09
g, 10.0 mmol) was dissolved in absolute EtOH (50 mL).
Saturated ethanolic KOH (1 mL) was added, and the mixture
was refluxed for 36 h under Ar. After cooling, H2O (20 mL)
was added, and the mixture was extracted with CH2Cl2 (3 ×
40 mL). The combined organic layers were washed with water
and dried over anhydrous MgSO4. The solvent was evapo-
rated, and the residue was purified by chromatography on
alumina (18 g), eluting with CH2Cl2/hexane (1:1), to afford 20a
as a slightly brown solid (1.26 g, 65%), which was recrystallized
from hexane: mp 129-130 °C (lit.10 mp 133-135 °C); 1H NMR
(acetone-d6) δ 10.93 (bs, 1H, NH), 8.20 (d, 1H, J ) 8.7 Hz,
H4), 7.89 (d, 1H, J ) 8.4 Hz, H8), 7.83 (d, 2H, J ) 8.7 Hz, H5
and H3), 7.66 (t, 1H, J ) 7.7 Hz, H7), 7.44 (t, 1H, J ) 7.2 Hz,
H6), 7.04 (q, 1H), 6.95 (q, 1H), 6.25 (q, 1H); 13C NMR (CDCl3)
δ 150.2, 147.7, 136.4, 131.7, 129.6, 128.1, 127.5, 126.6, 125.2,
121.3, 117.7, 110.2, 109.4.
2-(2′-P yr r olyl)-1,8-n a p h th yr id in e (20b). Following the
procedure described for 20a , a mixture of 2-aminonicotinal-
dehyde (18b, 2.44 g, 20.0 mmol), 2-acetylpyrrole (2.18 g, 20.0
mmol), and saturated ethanolic KOH (1 mL) was refluxed for
2 d under Ar to afford a crude product that was purified by
chromatography on alumina (18 g). The first fraction eluted
by CH2Cl2/hexane (1:1) was unreacted 2-acetylpyrrole. The
second fraction, eluting with CH2Cl2/EtOAc (1:1), afforded 20b
as a brown solid (2.43 g, 62%): mp 157-9 °C; 1H NMR (CDCl3)
δ 10.52 (s, 1H, NH), 9.01 (dd, 1H, H7), 8.08 (m, 1H, H5), 8.07
(d, 1H, H4), 7.76 (d, 1H, H3), 7.38 (dd, 1H, H6), 7.07 (s, 1H),
6.97 (s, 1H), 6.35 (q, 1H). Anal. Calcd for C19H14N2: C, 73.85;
H, 4.61; N, 21.54. Found: C, 73.77; H, 4.30; N, 21.28.
1- Meth yl-2-(2′-p yr r olyl)qu in olin iu m Iod id e (21). Fol-
lowing the procedure described for 3, 2-(2′-pyrrolyl)quinoline
(20a , 1.82 g, 9.4 mmol) was treated with methyl iodide (6.66
g, 46.9 mmol) for 3 d to afford 21 as a brown solid (0.79 g,
25%): mp 174-5 °C; 1H NMR (DMSO-d6) δ 12.58 (s, 1H, NH),
8.90 (d, 1H, J ) 9.0 Hz, H4), 8.44 (d, 1H, J ) 9.0 Hz, H8), 8.30
(d, 1H, J ) 8.1 Hz, H5), 8.16 (t, 1H, J ) 6.3 Hz, H7), 8.15 (d,
1H, J ) 9.0 Hz, H3), 7.91 (t, 1H, J ) 7.5 Hz, H6), 7.61 (q, 1H),
7.34 (q, 1H), 6.61 (q, 1H), 4.54 (s, 3H, NCH3); 13C NMR (DMSO-
d6) δ 150.6, 142.9, 139.7, 135.5, 130.3, 130.1, 128.7, 126.6,
124.5, 122.8, 121.8, 118.6, 113.0, 43.6. Anal. Calcd for
(d, 1H, J ) 7.5 Hz, H4), 7.57 (t, 1H, J ) 6.9 Hz, H5), 7.42 (d,
1H, J ) 7.8 Hz, H4′), 7.33 (d, 1H, J ) 8.1 Hz, H7′), 6.85 (t, 1H,
J ) 7.4 Hz, H6′), 6.69 (t, 1H, J ) 7.4 Hz, H5′), 4.59 (s, 3H,
NCH3), 2.80 (t, 2H), 2.58 (t, 2H), 2.21 (quintet, 2H); MS m/z
248 (M+), 234 (M - 14).
1-Met h yl-3,3′-et h en yl-2-(2′-in d olen ylid en e)-1,2-d ih y-
d r op yr id in e (9d ). Following the procedure described for 4,
1-methyl-11H-pyrido[2,3-a]carbazolium iodide (8d , 0.22 g, 0.6
mmol) was treated with ammonium hydroxide (10 mL) to
afford 9d as a red solid (0.11 g, 79%): mp 162 °C dec; 1H NMR
(DMSO-d6) δ 8.99-8.96 (overlapping, 2H, H4 and H6), 8.53 (d,
1H, J ) 8.1 Hz, 3′-CH), 8.21 (d, 1H, J ) 8.1 Hz, H4′), 7.80-
7.74 (overlapping, 2H, H5 and 3-CH), 7.47 (d, 1H, J ) 8.1 Hz,
H7′), 7.32 (t, 1H, J ) 7.5 Hz, H6′), 7.06 (t, 1H, J ) 7.4 Hz, H5′),
5.39 (s, 3H, NCH3); 13C NMR (DMSO-d6) δ 152.2, 143.2, 142.9,
139.7, 132.4, 129.0, 127.2, 123.9, 123.6, 123.3, 119.8, 118.5,
116.7, 116.3, 111.2, 49.7; MS m/z 232 (M+), 218 (M - 14).
12,13-Dih yd r o-5H-in d olo[3,2-c]a cr id in e (11). A mixture
of 1,2,3,4-tetrahydroacridin-4-one (10, 1.10 g, 5.6 mmol),
phenylhydrazine (0.65 g, 6.0 mmol), and acetic acid (1 drop)
in absolute EtOH (50 mL) was refluxed for 2 h. After cooling,
the phenylhydrazone as an orange solid was collected (1.02 g,
1
64%): mp 92-3 °C; H NMR (CDCl3) δ 8.03 (d, 1H, J ) 8.4
Hz, H5), 7.93 (s, 1H, H9), 7.72 (d, 1H, J ) 7.8 Hz, H8), 7.68 (t,
1H, J ) 6.9 Hz, H6), 7.51 (t, 1H, J ) 7.4 Hz, H7), 7.32 (d, 2H,
J ) 4.2 Hz, o-Ph), 7.31 (t, 2H, J ) 4.2 Hz, m-Ph), 7.35-7.31
(bs, 1H, NH), 6.87 (m, 1H, p-Ph), 3.03 (t, 2H, J ) 6.0 Hz, H3),
2.93 (t, 2H, J ) 6.0 Hz, H1), 2.06 (m, 2H, H2).
After polyphosphoric acid (PPA, 15 g) was heated at 150 °C
for 10 min and cooled to 120 °C, the phenylhydrazone of
1,2,3,4-tetrahydroacridin-4-one (7.20 g, 25.0 mmol) was added,
and the mixture was stirred for 30 min. The mixture was then
cooled, made basic with 50% NaOH solution, and extracted
with CH2Cl2. The organic layer was dried over anhydrous
MgSO4. The solvent was evaporated to afford 11 as a brown
yellow solid (4.76 g, 70%), which was recrystallized from
EtOH: mp 202-3 °C; 1H NMR (CDCl3) δ 10.07 (bs, 1Η, NH),
8.02 (d, 1H, J ) 8.4 Hz, H7), 7.91 (s, 1H, H11), 7.73 (d, 1H, J )
8.4 Hz, H10), 7.61-7.54 (overlapping, 2H, H8 and H1), 7.44 (t,
1H, J ) 7.8 Hz, H9), 7.21-7.09 (overlapping, 3H, H4, H3 and
H2), 3.31 (t, 2H, J ) 6.9 Hz, H12), 3.15 (t, 2H, J ) 6.9 Hz, H13).
Anal. Calcd for
C
19H14N2: C, 84.44; H, 5.19; N, 10.37.
C14H13N2I: C, 50.00; H, 3.87; N, 8.33. Found: C, 50.04; H,
Found: C, 84.69; H, 5.30; N, 10.17.
3.69; N, 8.20.
6-Meth yl-12,13-d ih yd r o-5H-in d olo[3,2-c]a cr id in iu m Io-
d id e (12). A mixture of 12,13-dihydro-5H-indolo[3,2-c]acridine
(11, 0.35 g, 1.3 mmol) and methyl iodide (2.5 g, 17.6 mmol) in
CH3CN (10 mL) was refluxed for 24 h. Additional methyl
iodide (2.5 g, 17.6 mmol) was added, and reflux was continued
an additional 24 h. A brown solid formed (0.11 g, 21%), which
was recrystallized from H2O to afford 12: mp 264-6 °C; H
NMR (DMSO-d6) δ 12.00 (bs, 1H, NH), 8.84 (s, 1H, H11), 8.49
(d, 1H, J ) 8.7 Hz, H7), 8.19 (d, 1H, J ) 7.8 Hz, H10), 8.07 (t,
1-Met h yl-2-(2′-p yr r olyl)-1,8-n a p h t h yr id in iu m Iod id e
(22). Following the procedure described for 3, 2-(2′-pyrrolyl)-
1,8-naphthyridine (20b, 1.62 g, 8.3 mmol) was treated with
methyl iodide (3.54 g, 24.9 mmol) for 1 h to afford 22 as an
orange solid (2.80 g, 100%): mp 287-9 °C (270 °C, turns
1
black); H NMR (DMSO-d6) δ 12.17 (s, 1H, NH), 9.36 (d, 1H,
1
J ) 5.4 Hz, H7), 9.02 (d, 1H, J ) 7.8 Hz, H5), 8.63 (d, 1H, J )
9.0 Hz, H4), 8.29 (d, 1H, J ) 8.7 Hz, H3), 7.93 (dd, 1H, J ) 6.0,
7.8 Hz, H6), 7.39 (s, 1H), 7.33 (s, 1H), 6.37 (s, 1H), 4.56 (s, 3H,

Tautomers Derived from 2-(2′-Pyridyl)indole
J . Org. Chem., Vol. 63, No. 12, 1998 4061
NCH3). Anal. Calcd for C13H12N3I: C, 46.29; H, 3.56; N, 12.46.
Found: C, 46.29; H, 3.38; N, 12.29.
tetrahydro-11H-pyrido[2,3-a]carbazole (25, 0.30 g, 1.4 mmol)
was treated with methyl iodide (2.0 g, 14 mmol) for 20 h to
afford 26 as a yellow solid (0.36 g, 73%): mp 283-5 °C; 1H
NMR (DMSO-d6) δ 11.93 (s, 1H, NH), 9.13-9.07 (overlapping,
2H, H2 and H4), 8.01 (d, 1H, J ) 8.7 Hz, H5), 7.86 (t, 1H, J )
6.3 Hz, H3), 7.84 (d, 1H, J ) 8.7 Hz, H6), 4.79 (s, 3H, N-CH3),
2.95 (t, 2H, CH2), 2.78 (t, 2H, CH2), 1.90 (quintet, 4H, CH2-
CH2). Anal. Calcd for C16H17N2I: C, 52.75; H, 4.67; N, 7.69.
Found: C, 52.63; H, 4.54; N, 7.51.
N-Met h yl-2-(2′-p yr r olylid en yl)-1,2-d ih yd r oq u in olin e
(23). Following the procedure described for 4, 1-methyl-2-(2′-
pyrrolyl)quinolinium iodide (21, 168 mg, 0.5 mmol) was treated
with ammonium hydroxide (10 mL) to afford 23 as a violet
solid (70 mg, 67%): mp 90 °C dec; 1H NMR (DMSO-d6) δ 8.23
(d, 1H, J ) 8.4 Hz, H3), 7.87 (d, 1H, J ) 8.1 Hz, H4), 7.84 (d,
1H, J ) 8.7 Hz, H8), 7.78 (d, 1H, J ) 7.8 Hz, H5), 7.71 (t, 1H,
J ) 7.8 Hz, H7), 7.44-7.40 (overlapping, 2H, H6 and H5′), 7.38
(d, 1H, J ) 3.3 Hz, H3′), 6.39 (d, 1H, J ) 3.6 Hz, H4′), 4.44 (s,
3H, NCH3); 13C NMR (DMSO-d6) δ 149.0, 145.2, 140.1, 134.9,
134.3, 131.7, 128.5, 125.1, 124.8, 124.2, 116.9, 116.8, 40.6; MS
m/z 208 (M+).
7,8,9,10-Tetr a h yd r o-11H-p yr id o[2,3-a ]ca r ba zole (25).
A mixture of 8-hydrazinoquinoline (24, 0.95 g, 6 mmol),
cyclohexanone (0.59, 6 mmol), and acetic acid (1 drop) in
absolute ethanol (15 mL) was refluxed for 20 h. The solvent
was evaporated to afford a dark oil. Chromatography on
alumina (20 g), eluting with CH2Cl2/hexane (1:1), provided the
quinolylhydrazone as an orange oil (1.16 g, 81%).
1-Meth yl-4′,5′,6′,7′-tetr a h yd r o-3,3′-eth en yl-2-(2′-in d ole-
n ylid en e)-1,2-d ih yd r op yr id in e (27). Following the proce-
dure described for 4, 7,8,9,10-tetrahydro-11H-pyrido[2,3-a]-
carbazolium iodide (26, 150 mg, 0.4 mmol) was treated with
ammonium hydroxide (10 mL) to afford 27 as a red solid (55
mg, 59%): mp 85-7 °C; 1H NMR (DMSO-d6) δ 8.52-8.48
(overlapping, 2H, H2 and H4), 7.69 (d, 1H, J ) 7.8 Hz, H5),
7.23 (t, 1H, J ) 6.9 Hz, H3), 7.17 (d, 1H, J ) 8.4 Hz, H6), 4.94
(s, 3H, N-CH3), 2.92 (t, 2H, CH2), 2.83 (t, 2H, CH2), 1.84
(quintet, 4H, CH2CH2); MS m/z 236 (M+), 218 (M - 18).
A mixture of the quinolylhydrazone of cyclohexanone (1.15
g, 4.8 mmol) and PPA (6.5 g) was heated at 150 °C for 1 h.
The mixture was cooled, made basic with 10% NaOH, and
extracted with CH2Cl2. The organic layer was dried over
anhydrous MgSO4. The solvent was evaporated to afford a
sticky solid. Chromatography on alumina (25 g), eluting with
CH2Cl2/hexane (1:1), provided 25 as a yellow solid (0.68 g,
64%), which was recrystallized from hexane: mp 147-8 °C
(lit.17 mp 151 °C); 1H NMR (CDCl3) δ 10.47 (bs, 1Η, NH), 8.79
(m, 1H, H2), 8.26 (dd, 1H, J ) 8.1 Hz, 1.2 Hz, H4), 7.69 (d, 1H,
J ) 8.4 Hz, H5), 7.42 (d, 1H, J ) 8.7 Hz, H6), 7.34 (dd, 1H, J
) 8.1 Hz, 4.5 Hz, H3), 2.81 (b, 2H, CH2), 2.76 (b, 2H, CH2),
1.92 (t, 4H, CH2CH2).
Ack n ow led gm en t. We would like to thank the
Robert A. Welch Foundation and the National Science
Foundation (CHE-9224686) for financial support of this
work. We would also like to thank Professor J acek
Waluk for discussions that led to this work and Profes-
sor Deborah Roberts for assistance with the mass
spectra.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
9a ,c and 33 and 1H and 13C NMR spectra of 4, 9b,d , 13, 23,
27, and 30 (17 pages). This material is contained in libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
7,8,9,10-Tetr a h yd r o-11H-p yr id o[2,3-a ]ca r ba zoliu m Io-
d id e (26). Following the procedure described for 3, 7,8,9,10-
(17) Dewar, M. J . S. J . Chem. Soc. 1944, 615.
J O980134J