Syntheses and characterization of N-(Indolyl)pyridinium salts and of their ylides

Article abstract of DOI:10.5560/ZNB.2014-3324

3-Methylindole reacts with pyridines in the presence of NBS to give indol-2-yl-pyridinium salts which were converted into their ylides by an anion exchange resin in its hydroxide form. Indol-3-amine was subjected to a nucleophilic ring transformation with pyrylium salts which resulted in the formation of indol-3-yl-pyridinium salts, the 2,4,6-trimethylpyridinium derivative of which proved to be unstable. The 2,4,6-triphenylpyridinium derivate was deprotonated to the corresponding ylide. The isomeric indol-2-yl and indol-3-yl derivatives are cycloimmonium ylides which are members of the compound class of heterocyclic mesomeric betaines (MB). By contrast, the ylide of indol-2-yl-pyrrolidinium is a cycloammonium ylide. It was prepared by reaction of 3-methylindole with pyrrolidine in the presence of NBS, followed by deprotonation.

Full text of DOI:10.5560/ZNB.2014-3324

Syntheses and Characterization of N-(Indolyl)pyridinium Salts and of
Their Ylides
Nazar Pidlypnyi, Sandra Kaul, Sebastian Wolf, Martin H. H. Drafz, and Andreas Schmidt
Clausthal University of Technology, Institute of Organic Chemistry, Leibnizstrasse 6, D-38678
Clausthal-Zellerfeld, Germany
Reprint requests to Prof. Dr. Andreas Schmidt. E-mail: schmidt@ioc.tu-clausthal.de
Z. Naturforsch. 2014, 69b, 605 – 614 / DOI: 10.5560/ZNB.2014-3324
Received December 11, 2013
3-Methylindole reacts with pyridines in the presence of NBS to give indol-2-yl-pyridinium salts
which were converted into their ylides by an anion exchange resin in its hydroxide form. Indol-3-
amine was subjected to a nucleophilic ring transformation with pyrylium salts which resulted in the
formation of indol-3-yl-pyridinium salts, the 2,4,6-trimethylpyridinium derivative of which proved
to be unstable. The 2,4,6-triphenylpyridinium derivate was deprotonated to the corresponding ylide.
The isomeric indol-2-yl and indol-3-yl derivatives are cycloimmonium ylides which are members
of the compound class of heterocyclic mesomeric betaines (MB). By contrast, the ylide of indol-
2-yl-pyrrolidinium is a cycloammonium ylide. It was prepared by reaction of 3-methylindole with
pyrrolidine in the presence of NBS, followed by deprotonation.
Key words: Mesomeric Betaines, Ylides, Mesoions, Immonium Ylides, Ammonium Ylides
Introduction
In either case, the anionic part is shown in form
of its simplified isoconjugate equivalent, the odd
Wittig introduced the term “ylid” (engl. also alternant hydrocarbon anion penta-1,3-dien-1-ide
“ylide”) into organic chemistry as a combination of the VIII. Characteristically, the cationic part of 1 and
syllables “yl” (organic radical such as methyl) which 2 is joined through a starred position to the anionic
suggests a free valence and the syllable “id” which ex- equivalent. These are active positions of the highest
presses a negative charge (such as in “acetylid”) [1]. occupied molecular orbital (HOMO). Resonance
In ylides, represented by the general formula I, forms of ylides and conjugated mesomeric betaines
a carbanion is directly attached to a heteroatom bear- can be drawn which display common atoms for either
ing a positive charge. According to Zugra˘vescu and charge (vide infra). By contrast, in cross-conjugated
Petrovanu, distinct classes of N-ylides can be distin- (CCMB) as well as pseudo-cross-conjugated me-
guished, i. e. ammonium-ylides (II), cycloammonium- someric betaines (PCCMB), for which 3 and 4 are
ylides (III), immonium-ylides (IV), cycloimmonium- given as examples, respectively, the cationic parts
ylides (V), nitrile-ylides (VI), and diazonium-ylides are bound to the negative part through unstarred
(VII) [1] (Fig. 1).
positions [2 – 6]. The isoconjugate equivalent of the
Ollis, Stanforth, and Ramsden regarded carboxylate group, i. e. propen-1-id IX, is shown.
cycloimmonium-ylides (V) of heteroaromatics as These unstarred positions are inactive positions of
one of four distinct classes of heterocyclic me- the HOMO, and this architecture causes a charge
someric betaines [2 – 4]. They are distinguished separation in the ground state of the molecules and
from conjugated heterocyclic mesomeric betaines determines the chemical properties. Thus, whereas
in such a way that ylides can satisfactorily be ylides and conjugated heterocyclic mesomeric
represented by 1,2-dipolar resonance structures. betaines are versatile 1,3-dipoles in heterocyclic
Compound 1 is an example of such an ylide (Fig. 2). chemistry [1 – 4], cross-conjugated systems undergo
Compound 2 is closely related but belongs to the predominantly 1,4-dipolar cycloadditions [2 – 4, 7 – 9]
class of conjugated mesomeric betaines (CMB). and can therefore be applied as switchable devices in
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N. Pidlypnyi et al. · N-(Indolyl)pyridinium Salts and Their Ylides
X
N
N
N
N
N
N
N
I
II
III
IV
V
VI
VII
X = N, S, P, etc.
Fig. 1. Classes of ylides.
O
R
N
R
O
O
O
N
N
O
O
O
N
R
N
N
O
R
R
R
R
4
1
3
2
ylide
CMB
CCMB
PCCMB
*
*
*
*
*
Fig. 2. Four distinct classes
of mesomeric betaines.
HOMO of VIII
HOMO of IX
VIII
IX
Fig. 3. Architecture of in-
dol-2-yl and indol-3-yl py-
ridinium betaines.
materials chemistry [10, 11]. Cleavage of the union meric ylides which are closely related to conjugated
bond connecting the positive and the negative part heterocyclic mesomeric betaines. They are generated
of cross-conjugated mesomeric betaines to abnormal by joining π-conjugated positive partial structures such
N-heterocyclic carbenes (aNHC) is rare [12]. By as pyridinium rings to the 2- or to the 3-position of the
contrast, the generation of normal N-heterocyclic indol-1-ide partial structure (c. f. XI) which are both
carbenes (NHC) by thermal decarboxylations of active positions of the highest occupied molecular or-
pseudo-cross-conjugated mesomeric betaines, which bital (HOMO) according to DFT calculations. To the
can be regarded as heterocumulene adducts of best of our knowledge, only three examples of the lat-
NHCs [13], has been widely applied in organometallic ter type of compound have been published to date (vide
chemistry [14 – 17], organocatalysis [18 – 22], and infra).
synthesis of heterocycles [23 – 27]. Review articles
on betaine-carbene interconversions have appeared taines [30] and N-heterocyclic carbenes [31] we report
recently [28, 29]. here on the synthesis and characterization of new 1-
In continuation of our work on mesomeric be-
The indol-1-ide anion X is isoconjugated with an (pyridinium)indol-2-yl-1-ides and of an additional rep-
odd, non-alternant hydrocarbon anion (Fig. 3). There- resentative of the isomeric 1-(pyridinium)indol-3-yl-1-
fore, it gives the unique possibility to study two iso- ides.
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N. Pidlypnyi et al. · N-(Indolyl)pyridinium Salts and Their Ylides
607
Scheme 1. Synthesis of indol-2-yl-pyridinium salts and of their ylides.
1
Results and Discussion
between δ = 11.70 and 12.43 ppm in the H NMR
spectra measured in [D6]DMSO disappears on depro-
Reaction of 3-methylindole 5 with pyridine (6a), tonation. Only compound 7a was mentioned previ-
4-methylpyridine (6b), 4-dimethylaminopyridine (6c), ously in the literature [32]. The ylide formation causes
and 4-(pyrrol-1-yl)pyridine (6d) in the presence of an upfield shift of the indole 1H NMR resonances. As
N-bromosuccinimide resulted in the formation of the an example, the signal of 4-H is shifted from δ = 7.63
pyridinium salts 7a–d in moderate to excellent yields (7c) to 7.28 ppm (8c) in deuterated DMSO.
(Scheme 1). Treatment of solutions of the salts 7a–d
A selection of mesomeric structures of the ylide
in a mixture of water and methanol with the anion ex- 8a is shown in Fig. 4. As already mentioned, com-
change resin Amberlite IRA-96 in its hydroxide form mon atoms for positive as well as negative charges
gave the ylides 8a–d in very good to excellent yields exist, and this is a characteristic feature of members
as orange to dark-red compounds. The resonance fre- of the class of conjugated heterocyclic mesomeric be-
quency of the NH group of 7a–d which is detectable taines and ylides. The characteristic dipole type which
Fig. 4. Architecture of in-
dol-2-yl pyridinium ylides.
HOMO (8a)
LUMO (8a)
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N. Pidlypnyi et al. · N-(Indolyl)pyridinium Salts and Their Ylides
Scheme 2. Synthesis of a cycloammonium ylide.
serves for the identification of betaine classes [2] position of the highest occupied molecular orbital
is also shown. The calculated dihedral angle de- (HOMO).
creases by approximately 28◦ to 11.2◦ on ylide for-
In a similar procedure, 3-methylindole (5) and N-
mation from the salt in accordance with a higher methylpyrrolidine (9) were converted into the 1-(indol-
degree of conjugation between the two parts of the 2-yl)-1-methylpyrrolidinium bromide (10) which was
molecule. The bond connecting the two parts was cal- deprotonated to the ylide 1-methyl-1-(pyrrolidinio)-
culated to be approximately 142 pm long. This value indolide (11) in almost quantitative yield by an anion
is longer than a Csp2 –N bond (138 pm) as found exchange resin (Scheme 2).
in formamide. The highest occupied molecular or-
In the ammonium ylide 11 the positive charge is not
bital (HOMO) and the lowest unoccupied molecu- delocalized. As shown in Fig. 5, in the resonance forms
lar orbital (LUMO) are located essentially in sep- the charges are strictly delocalized in separate parts
arate parts of the common π-electron system, i. e. of the molecule. The characteristic dipole type of cy-
in the indole ring (HOMO) and the pyridinium ring cloammonium ylides (c. f. III in Fig. 1) is also shown.
(LUMO). In accordance with the definition, position As expected, the dihedral angle is larger than in the
2 of the indole anion partial structure is an active ylide described above, and the bond length connecting
Fig. 5. Architecture of am-
monium ylides.
HOMO (11)
LUMO (11)
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N. Pidlypnyi et al. · N-(Indolyl)pyridinium Salts and Their Ylides
609
Scheme 3. Synthesis of an indol-3-yl pyridinium ylide.
the two partial structures of the molecule is consider- which was not isolated, was accomplished by heating
ably longer than in conjugated systems. On ylide for- in anhydrous toluene, followed by hydrolysis which
mation from the salt, the dihedral angle changes from resulted in the formation of the hydrochloride of 3-
86.2◦ to 104.8◦ according to DFT calculations. Corre- aminoindole (14). Nucleophilic ring transformation of
spondingly, there are marked differences in the frontier the pyrylium salts 15a, b with 14 resulted in the for-
orbital profiles in comparison to the ylides described mation of the indol-3-yl-pyridinium salts 16a, b. The
above. The HOMO and LUMO are located in the in- trimethyl derivative 16a, however, could not be iso-
dole moiety as expected, plus small contributions to lated in pure form. Attempts to recrystallize the sam-
the LUMO of the ylide bond (Fig. 5).
ple met with difficulties, as the product decomposed in
We next tried a synthesis of indol-3-yl-pyridinium a variety of solvents. The salt 16b, however, proved to
salts by nucleophilic ring transformation of 1H- be stable and was fully characterized. Its ylide was ob-
indol-3-amine with pyrylium salts. 1H-Indol-3-yl- tained after treatment with methanolic potassium hy-
pyridinium, -quinolinium and -isoquinolinium salts droxide as a dark-green solid in good yield.
have been prepared before via the highly explosive
The charges in ylide 17b are delocalized over the
3-phenyliodonioindole acetate, prepared by treatment entire π-system according to the resonance forms
of indole with phenyl iodosoacetate, which was first (Fig. 6). The characteristic dipole type is identical with
subjected to an anion exchange and then treated with the dipole of conjugated mesomeric betaines as well
the corresponding heteroaromatics [32]. We started as with the isomeric indol-2-yl derivative described be-
our synthesis from 1H-indole-3-carbohydrazide (12) fore. Due to steric hindrance the dihedral angle is much
which was transformed into the 1H-indole-3-carbonyl larger than in 2-pyridinio-indolide described above.
azide (13) according to modified literature procedures However, conjugation between the two parts of the
using sodium nitrite in acetic acid [33] (Scheme 3). molecule induces a considerably decrease of the dihe-
Rearrangement of 13 to the 3-isocyanato-1H-indole, dral angle on conversion of the salt (71.3◦) into the
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N. Pidlypnyi et al. · N-(Indolyl)pyridinium Salts and Their Ylides
Fig. 6. Architecture of the
indol-3-yl pyridinium ylide
17.
HOMO (17)
LUMO (17)
ylide (51.8◦) according to the DFT calculation. As ex- Experimental Section
pected the HOMO is essentially located in the indole
Nuclear magnetic resonance (NMR) spectra were mea-
sured with Bruker Avance 400 MHz and Bruker Avance III
600 MHz instruments. 1H NMR spectra were recorded at
400 MHz or 600 MHz, 13C NMR spectra at 100 MHz or
150 MHz, with the solvent peak or tetramethylsilane used
as the internal reference. Multiplicities are described by
using the following abbreviations: s = singlet, d = doublet,
t = triplet, q = quartet, and m = multiplet. The mass spec-
tra were measured with a Varian 320 MS Triple Quad
GC/MS/MS with a Varian 450-GC. The electrospray ioniza-
tion mass spectra (ESIMS) were measured with an Agilent
LCMSD series HP 1100 instrument with APIES. Samples for
ring, whereas the LUMO has its largest coefficients
is the pyridinium ring. Characteristically, position 3 of
the indole partial structure is an active position of the
HOMO, so that one of the characteristics of ylides be-
longing to the class of heterocyclic mesomeric betaines
is fulfilled.
In summary, we prepared indol-2-yl and indol-3-yl
pyridinium salts and converted them into their ylides
which are isomeric members of the class of hetero-
cyclic mesomeric betaines. By contrast, the indol-2-yl
pyrrolidinium salt is an ammonium ylide.
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N. Pidlypnyi et al. · N-(Indolyl)pyridinium Salts and Their Ylides
611
ESI mass spectrometry were sprayed from methanol at 0 V 9.05 (d, 2H, 20/60-H, J = 8.1 Hz), 11.70 (s, 1H, N-H) ppm. –
fragmentor voltage unless otherwise noted. Melting points 13C NMR ([D6]DMSO): δ = 7.9, 22.6, 107.7, 112.9, 120.9,
are uncorrected and were determined in an apparatus ac- 122.0, 126.2, 128.7, 130.2, 132.8, 136.2, 145.6, 163.4 ppm. –
cording to Dr. Tottoli (Büchi). Yields are not optimized. All IR (KBr): ν = 758, 819, 1237, 1337, 1368, 1472, 1633, 2856,
density-functional theory (DFT) calculations were carried 2967 cm−1. – MS ((+)-ESI): m/z (%) = 223 (100) [M–Br]+.
out by using the JAGUAR 7.7.107 software [34] running on – HRMS ((+)-ESI): m/z = 223.1231 (calcd. 223.1235 for
Linux 2.6.18-238.el5 SMP (x86_64) on two AMD Phenom [C15H15N2]+).
II X6 1090T processor workstations (Beowulf cluster) paral-
4-Dimethylamino-1-(3-methylindol-2-yl)pyridinium
bromide (7c)
lelized with OpenMPI 1.3.4. MM2 optimized structures were
used as starting geometries. Complete geometry optimiza-
tions were carried out on the implemented LACVP* (Hay-
Wadt effective core potential (ECP) basis on heavy atoms,
N31G6* for all other atoms) basis set and with the B3LYP
density functional. All calculated structures were proven to
be true minima by the absence of imaginary frequencies.
Plots were obtained using MAESTRO 9.1.207, the graphical
interface of JAGUAR. Thermodynamic corrections were es-
timated from unscaled frequencies, using standard formulae
in the ideal gas harmonic oscillator approximation as imple-
mented in JAGUAR, and refer to a standard state of 298.15 K
and 1 mol L−1 concentration.
Yield: 0.48 g (95%); m. p. 235 ◦C.
–
1H NMR
([D6]DMSO): δ = 2.22 (s, 3 H, Me), 3.32 (s, 6 H, Me2N),
7.15 (ddd, 1H, 5-H, J = 8.1/7.2/1.0 Hz), 7.22 (d, 2H, 30/50-
H, J = 7.8 Hz), 7.27 (ddd, 1H, 6-H, J = 8.1/7.2/1.1 Hz),
7.44 (ddd, 1H, 7-H, J = 8.1/0.9/0.9 Hz), 7.63 (d, 1H, 4-H,
J = 8.1 Hz), 8.52 (d, 2H, 20/60-H, J = 7.8 Hz), 12.02 ppm (s,
1 H, N-H). – 13C NMR ([D6]DMSO): δ = 7.5, 66.3, 103.7,
107.7, 111.7, 119.3, 119.9, 123.3, 126.9, 131.6, 133.3, 142.4,
156.0 ppm. – IR (KBr): ν = 3419, 1705, 1645, 1575, 1458,
1340, 1219, 1176, 1011, 812, 753, 528 cm−1. – MS ((+)-
ESI): m/z (%) = 252.1 (100) [M–Br]+. – HRMS ((+)-ESI):
m/z = 252.1496 (calcd. 252.1501 for [C16H18N3]+).
General procedure for the synthesis of the salts 7a–d
A solution of 3-methylindole (5) (2.0 mmol) and the
corresponding pyridine (2.0 mmol) in 10 mL of anhy-
drous benzene was treated at r. t. within 15 min with N-
bromosuccinimide (1.5 mmol) whereupon a precipitate was
formed. The mixtures were stirred for additional 75 min and
then heated at reflux temperature for 1 h. The solids were fil-
tered off and washed with hot benzene.
4-(Pyrrolidin-1-yl)-1-(3-methylindol-2-yl)pyridinium
bromide (7d)
Yield: 0.660 g (49%); m. p. 252 ◦C.
–
1H NMR
([D6]DMSO): δ = 2.06 – 2.07 (m, 4H, -CH2-), 2.22 (s,
3H, Me), 3.60 – 3.64 (m, 4H, -CH2-), 7.04 (d, 2H, 30/50-
H, J = 8.12 Hz), 7.15 (ddd, 1H, 5-H, J = 8.1/7.1/1.0 Hz),
7.26 (ddd, 1H, 6-H, J = 8.1/7.1/1.0 Hz), 7.43 (d, 1H, 7-
H, J = 8.1 Hz), 7.62 (d, 1H, 4-H, J = 8.1 Hz), 8.45 (d, 2H,
20/60-H, J = 7.8 Hz), 12.00 (s, 1H, N-H) ppm. – 13C NMR
([D6]DMSO): δ = 7.5, 24.8, 48.6, 104.0, 108.3, 111.3, 119.7,
120.3, 123.3, 126.9, 131.7, 133.3, 142.4, 153.3 ppm. – IR
(KBr): ν = 503, 768, 817, 1008, 1176, 1220, 1346, 1454,
3053 cm−1. – MS ((+)-ESI): m/z (%) = 278 (100) [M–Br]+.
– HRMS ((+)-ESI): m/z = 278.1653 (calcd. 278.1657 for
[C18H20N3]+).
1-(3-Methylindol-2-yl)pyridinium bromide (7a)
Yield: 0.40 g (98%); m. p. 225 ◦C.
–
1H NMR
([D6]DMSO): δ = 2.35 (s, 3 H, Me), 7.19 – 7.24 (m, 1 H, 5-
H), 7.32 – 7.38 (m, 1 H, 6-H), 7.53 (d, 1 H, 7-H, J = 8.3 Hz),
7.73 (d, 1 H, 4-H, J = 7.8 Hz), 8.40 (dd, 2 H, 30/50-H,
J = 7.8 Hz, J = 6.7 Hz), 8.81 – 8.89 (m, 1 H, 40-H), 9.38 (dd,
2 H, 20/60-H, J = 6.7 Hz, J = 1.1 Hz), 12.40 ppm (s, 1 H, N-
H). – 13C NMR ([D6]DMSO): δ = 7.7, 105.7, 112.1, 120.0,
120.4, 124.4, 126.8, 128.3, 131.8, 133.9, 145.5, 147.1 ppm.
– IR (KBr): ν = 3432, 3001, 1623, 1476, 1449, 1336, 1153,
941, 892, 748, 727, 710, 669, 631, 530, 477 cm−1. – MS
((+)-ESI): m/z (%) = 209.1 (100) [M–Br]+. – HRMS ((+)-
ESI): m/z = 209.1081 (calcd. 209.1079 for [C14H13N2]+).
N-Methyl-1-(3-methylindol-2-yl)pyrrolidinium bromide (10)
Yield: 0.358 g (32%) of a colorless solid; m. p. 163 ◦C.
1
– H NMR ([D6]DMSO): δ = 2.12 – 2.33 (m, 4H, -CH2-),
2.47 (s, 3H, Me), 3.50 (s, 3H, Me), 4.11 – 4.18 (m, 2H,
-CH2-), 4.36 – 4.42 (m, 2H, -CH2-), 7.14 (ddd, 1H, 5-H, J =
8.1/7.1/1.0 Hz), 7.27 (ddd, 1H, 6-H, J = 8.3/7.1/1.0 Hz),
4-Methyl-1-(3-methylindol-2-yl)pyridinium bromide (7b)
Yield: 0.692 g (85%); m. p. 245 ◦C.
–
1H NMR 7.45 (d, 1H, 7-H, J = 8.3 Hz), 7.64 (d, 1H, 8-H, J = 8.1 Hz),
([D6]DMSO): δ = 2.39 (s, 3H, Me), 2.83 (s, 3H, Me0), 7.22 12.02 (s, 1H, N-H) ppm. – 13C NMR ([D6]DMSO): δ = 9.3,
(ddd, 1H, 5-H, J = 8.1/7.0/1.1 Hz), 7.35 (ddd, 1H, 6-H, 20.9, 53.4, 66.8, 101.7, 112.0, 119.2, 120.1, 123.8, 127.2,
J = 8.1/7.0/1.1 Hz), 7.48 (d, 1H, 7-H, J = 8.1 Hz), 7.69 132.8, 134.7 ppm. – IR (KBr): 761, 800, 924, 1230, 1342,
(d, 1H, 4-H, J = 8.1 Hz), 8.17 (d, 2H, 30/50-H, J = 8.1 Hz), 1460, 1711, 2879, 2980, 3037 cm−1. – MS ((+)-ESI): m/z
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N. Pidlypnyi et al. · N-(Indolyl)pyridinium Salts and Their Ylides
(%) = 215 (100) [M–Br]+. – HRMS ((+)-ESI): m/z = MS ((+)-ESI): m/z = 252.1 [M+H]+. – HRMS ((+)-ESI):
215.1243 (calcd. 215.1548 for [C14H19N2]+).
m/z = 252.1504 (calcd. 252.1501 for [C16H18N3]+).
General procedure for the preparation of the ylides 8a–d
3-Methyl-2-[4-(pyrrolidin-1-yl)pyridinio]-indol-1-ide (8d)
Yield: 0.147 g (98%) of a yellow solid; m. p. 105 ◦C. –
1H NMR ([D6]DMSO): δ = 2.03 – 2.07 (m, 4H, -CH2-),
2.23 (s, 3H, Me), 3.22 – 3.26 (m, 4H, -CH2-), 7.02 (d, 2H,
30/50-H, J = 7.70 Hz), 7.07 (dd, 1H, 5-H, J = 7.1/7.1 Hz),
7.18 (dd, 1H, 6-H, J = 8.0/7.1 Hz), 7.40 (d, 1H, 7-H, J =
8.0 Hz), 7.56 (d, 1H, 4-H, J = 7.1 Hz), 8.17 (d, 2H, 20/60-
H, J = 7.70 Hz) ppm. – 13C NMR ([D6]DMSO): δ = 7.3,
24.6, 48.7, 103.5, 108.2, 111.7, 119.3, 120.5, 123.4, 127.2,
133.5, 142.0, 148.2 ppm. – IR (KBr): ν = 749, 1180, 1223,
1454, 1566, 1650, 2975, 3057 cm−1. – MS ((+)-ESI): m/z =
278.1 [M+H]+. – HRMS ((+)-ESI): m/z = 278.1661 (calcd.
278.1657 for [C18H19N3]+).
A sample of 60 mL of the anion exchange resin
Amberlite® IRA-96 was filled into a column and washed
with 3 L of water. Then the resin was treated with 200 mL of
an 8% aqueous NaOH solution over a period of 8 h. Finally,
the resin was washed with water until pH = 7 was reached.
The salts 7a–d (0.66 mmol) were dissolved in water-MeOH
(1 : 1), given on the resin and eluted with the same solvent
mixture. The solvent was finally distilled off in vacuo to give
the ylides.
3-Methyl-2-(1-pyridinio)-indol-1-ide (8a)
Yield: 0.148 g (99%) of a dark-red solid; m. p. 75 ◦C. –
1H NMR ([D6]DMSO): δ = 2.38 (s, 3H, Me), 7.02 (ddd, 1H,
5-H, J = 8.1/7.1/1.0 Hz), 7.14 (ddd, 1H, 6-H,J = 8.2 / 7.1 /
1.0 Hz), 7.44 (d, 1H, 7-H, J = 8.2 Hz), 7.59 (d, 1H, 4-H, J =
8.1 Hz), 8.24 (dd, 2H, 30/50-H, J = 7.8/5.8 Hz), 8.64 (d, 1H,
40-H, J = 7.8 Hz), 9.36 (d, 2H, 20/60-H, J = 5.8 Hz) ppm. –
13C NMR ([D6]DMSO): δ = 8.5, 102.1, 114.1, 118.6, 119.3,
122.3, 127.9, 128.4, 135.8, 137.4, 144.2, 145.0 ppm. – IR
(KBr): ν = 678, 745, 1071, 1150, 1264, 1335, 1454, 1625,
2859, 3057 cm−1. – MS ((+)-ESI): m/z = 209.1 [M+H]+.
– HRMS ((+)-ESI): m/z = 209.1077 (calcd. 209.1079 for
[C14H12N2]+).
3-Methyl-2-(1-methylpyrrolidinio)-indol-1-ide (11)
Yield: 0.108 g (98%) of a brownish oil. – 1H NMR
([D6]DMSO): δ = 2.13 – 2.28 (m, 4H, -CH2-), 2.44 (s, 3H,
Me), 3.47 (s, 3H, Me), 4.23 – 4.28 (m, 4H, -CH2-), 6.95
(dd, 1H, 5-H, J = 8.0/7.7 Hz), 7.04 (dd, 1H, 6-H, J =
8.0/7.7 Hz), 7.34 (d, 1H, 7-H, J = 7.7 Hz), 7.48 (d, 1H, 4-H,
J = 8.0 Hz) ppm. – 13C NMR ([D6]DMSO): δ = 9.9, 21.0,
53.1, 66.0, 98.6, 113.8, 117.8, 118.2, 120.8, 128.8, 135.8,
139.4 ppm. – IR (KBr): ν = 752, 1344, 1460, 1710, 2920,
2977, 3015 cm−1
Preparation of 1H-indole-3-carbonyl azide (13)
sample of 1 g (5.71 mmol) of 1H-indole-3-
.
3-Methyl-2-(4-methylpyridinio)-indol-1-ide (8b)
Yield: 0.147 g (98%) of a brownish oil. – 1H NMR
([D6]DMSO): δ = 2.32 (s, 3H, Me), 2.75 (s, 3H, Me), 7.20
(ddd, 1H, 5-H, J = 8.1/7.1/1.1 Hz), 7.33 (ddd, 1H, 6-H, J =
8.1/7.1/1.1 Hz), 7.50 (d, 1H, 7-H, J = 8.1 Hz), 7.70 (d, 1H,
4-H, J = 8.05 Hz), 8.20 (d, 2H, 30/50-H, J = 6.7 Hz), 9.18 (d,
2H, 20/60-H, J = 6.7 Hz) ppm. – 13C NMR ([D6]DMSO):
δ = 7.6, 21.9, 107.4, 112.1, 119.8, 120.3, 124.2, 128.5,
129.7, 131.3, 138.4, 144.2, 161.3 ppm. – IR (KBr): ν = 749,
1333, 1468, 1635, 2857, 2973, 3057 cm−1. – MS ((+)-ESI):
m/z = 223.1 [M+H]+. – HRMS ((+)-ESI): m/z = 223.1238
(calcd. 223.1235 for [C15H14N2]+).
A
carbohydrazide (12) was dissolved in 50 mL of 50%
acetic acid. After cooling to –5 ◦C, a solution of 394 mg
(5.71 mmol) of sodium nitrite in water was added dropwise,
whereupon the color of the solution changed from orange to
brown. After 10 min of stirring the solid was filtered off and
washed with water. The crude product was dried in vacuo.
1
Yield: 934 mg (88%). – H NMR (400 MHz, [D6]DMSO):
δ = 11.66 (s, 1H, NH), 9.81 (s, 1H, NHCH), 8.15 (d,
1H, Ar-H, J = 9.0 Hz), 7.48 (d, 1H, Ar-H, J = 7.9 Hz),
7.21 – 7.16 (m, 1H, Ar-H), 7.16 – 7.11 (m, 1H, Ar-H) ppm.
All spectroscopic data are agreement to those reported in the
literature [33].
3-Methyl-2-(4-dimethylaminopyridinio)-indol-1-ide (8c)
Yield: 0.138 g (83%) of a yellow solid; m. p. 77 ◦C. –
1H NMR ([D6]DMSO): δ = 2.30 (s, 3H, Me), 3.23 (s, 6H,
Me2N), 6.68 (m, 1H, 5-H), 6.74 (m, 1H, 6-H), 7.05 (d, 2H,
20/60-H, J = 7.8 Hz), 7.22 (d, 1H, 7-H, J = 7.9 Hz), 7.28 (d,
1H-Indol-3-amine hydrochloride (14)
Under an inert atmosphere a sample of 8.8 g (47.27 mmol)
1H, 4-H, J = 7.3 Hz), 8.57 (d, 2H, 30/50-H, J = 7.8 Hz) ppm. of 1H-indole-3-carbonyl azide (13) was suspended in
–
13C NMR ([D6]DMSO): δ = 9.2, 38.6, 94.4, 107.2, 115.5, 300 mL of anhydrous toluene. After heating at 70 ◦C over
116.0, 117.3, 117.9, 130.5, 141.2, 141.6, 141.8, 155.1 ppm. a period of 5 h the solvent was distilled off in vacuo, and
– IR (KBr): 3056, 1644, 1372, 1214, 822, 748 cm−1. – the resulting dark residue was treated with 100 mL of THF
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613
and 20 mL of conc hydrochloric acid. After stirring at 40 ◦C 1-(1H-Indol-3-yl)-2,4,6-triphenylpyridinium tetrafluoro-
for 1 h, the solvent mixture was distilled off in vacuo, the borate (16b)
residue was treated with water and extracted three times
Yield: 1.39 g (92%); m. p. 271 ◦C.
–
1H NMR
with diethyl ether. The aqueous solution was finally con-
centrated in vacuo, and the resulting brownish crystals were
filtered off and dried. Yield: 7.08 g (89%). – 1H NMR
([D6]DMSO): δ = 11.45 (br s, 1H, NH), 10.40 (s, 3H,
NH3), 7.69 (d, 1H, CH-CH-C, J = 8.1 Hz), 7.51 (d, 1H,
NHCH, J = 2.7 Hz), 7.45 (d, J = 8.2 Hz, 1H, CH-CH-C),
7.19 (ddd, 1H, CHCHCH, J = 8.2/7.1/1.1 Hz, 1H), 7.10
(ddd, 1H, CHCHCH, J = 8.1/7.1/1.0 Hz) ppm. – 13C NMR
([D6]DMSO): δ = 134.59, 122.25, 121.28, 119.39, 119.09,
117.67, 112.06, 106.84 ppm. All spectroscopic data are in
agreement to those reported in the literature [33].
([D6]DMSO): δ = 11.87 (s, 1H, NH), 8.66 (s, 2H, 30/50-
H), 8.38 (d, 2H, Ar-H, J = 7.1 Hz), 7.72 – 7.64 (m, 3H,
Ar-H), 7.53 (s, 1H, Ar-H), 7.49 (d, J = 6.9 Hz, 4H, Ar-
H), 7.42 (d, 1H, Ar-H, J = 7.9 Hz), 7.33 – 7.18 (m, 7H,
Ar-H), 7.00 (dd, 1H, Ar-H, J = 7.4/7.4 Hz), 6.93 (dd, 1H,
Ar-H, J = 7.4/7.4 Hz) ppm. – 13C NMR ([D6]DMSO):
δ = 158.02, 155.31, 133.46, 133.37, 133.30, 132.46, 129.84,
129.65, 128.91, 128.82, 127.72, 126.02, 125.19, 122.81,
122.10, 120.36, 116.99, 115.35, 112.03 ppm. – ATR-IR: ν =
3364, 1619, 1575, 1412, 1241, 1053, 764, 748, 699, 648,
621, 530, 429 cm−1. – MS ((+)-ESI): m/z = 423.1 [M]+.
– HRMS ((+)-ESI): m/z = 423.1857 (calcd. 423.1861 for
[C31H23N2]+).
Nucleophilic ring transformation of the pyrylium salts
15a, b to the pyridinium salts 16a, b
A
solution of 0.5 g (2.97 mmol) of 1H-indol-3-
3-(2,4,6-Triphenylpyridinium-1-yl)-indol-1-ide (17)
amine hydrochloride, 1.292 g (3.26 mmol) of 2,4,6-
triphenylpyrylium tetrafluoroborate or 0.685 g (3.26 mmol)
of 2,4,6-trimethylpyrylium-tetrafluoroborate and 0.468 g
(5.93 mmol) of sodium acetate in 40 mL of ethanol was
heated at reflux temperature over a period of 24 h and
then evaporated to dryness. The resulting residue was then
dissolved in ethanol to give a concentrated solution which
was poured into diethyl ether at 0 ◦C. The resulting solid
was filtered off and dried.
A sample of 250 mg (0.59 mmol) of the salt 16b was
dissolved in a solution of 33 mg (0.59 mmol) of KOH in
10 mL of MeOH. After 10 min at r. t. with stirring the so-
lution was treated with 20 mL of water whereupon a dark-
green solid formed which was filtered off, washed with small
amounts of cold water, and dried in vacuo. Yield: 184 mg
(74%); m. p. 249 ◦C. – 1H NMR ([D6]DMSO): δ = 8.63
(s, 2H, 30/50-H), 8.37 – 8.32 (m, 2H, Ar-H), 7.72 – 7.64
(m, 3H, Ar-H), 7.52 – 7.46 (m, 5H, Ar-H), 7.41 (d, 1H,
Ar-H, J = 7.9 Hz), 7.32 – 7.21 (m, 7H, Ar-H), 7.04 – 6.98
(m, 1H, Ar-H), 6.97 – 6.91 (m, 1H, Ar-H) ppm. – 13C
1-(1H-Indol-3-yl)-2,4,6-trimethylpyridinium tetrafluoro-
borate (16a)
The crude product contained impurities. All attempts to NMR ([D6]DMSO): δ = 157.99, 155.39, 133.44, 133.32,
recrystallize the salt caused decomposition so that a full char- 132.49, 129.89, 129.68, 128.89, 128.77, 127.75, 126.05,
1
acterization failed. – H NMR ([D6]DMSO): δ = 12.43 (s, 125.19, 122.85, 122.24, 120.47, 116.99, 115.44, 112.05 ppm.
1H, NH), 7.98 (s, 2H, 30/50-H), 7.84 (s, 1H, NH-CH), 7.62 – ATR-IR: ν = 1619, 1549, 1240, 1055, 888, 764, 748,
(d, 1H, Ar-H, J = 8.4 Hz), 7.29 (m, 2H, Ar-H), 7.15 (m, 1H, 699, 530, 430 cm−1. – MS ((+)-ESI): m/z (%) = 423.1
Ar-H), 2.63 (s, 3H, Me), 2.36 (s, 6H, Me) ppm. – MS ((+)- (100) [M+H]+. – HRMS ((+)-ESI): m/z = 423.1864 (calcd.
ESI): m/z = 237[M]+.
423.1861 for [C31H23N2]+).
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