Preparation and characterization of aryl or heteroaryl(3-indolyl)methylium o-benzenedisulfonimides

Article abstract of DOI:10.1021/jo300099y

An initial study has been accomplished into the synthetic feasibility of the preparation of diarylcarbenium salt via the direct coupling of aryl (or heteroaryl) aldehydes and arenes (or heteroaryl analogues) in the presence of a strong organic Bronsted acid. A number of stabilized aryl or heteroaryl(3-indolyl)carbenium ions, never previously prepared in the solid state, have been isolated in excellent yields as highly stable o-benzenedisulfonimide salts and have been fully characterized. Their purity has been proven by spectroscopic methods and chemical reduction with NaBH ₄. An X-ray crystal structure analysis has been performed on one of the products: an azafulvenium species was shown to be the exclusive structure in the solid state.

Full text of DOI:10.1021/jo300099y

Article
pubs.acs.org/joc
Preparation and Characterization of Aryl
or Heteroaryl(3-indolyl)methylium o-Benzenedisulfonimides
Margherita Barbero,*,† Silvano Cadamuro,† Fabrizio Cauda,† Stefano Dughera,† Giuliana Gervasio,‡
and Paolo Venturello†
†Dipartimento di Chimica, Universita
̀
di Torino, Via P. Giuria 7, 10125 Torino, Italy
‡Dipartimento di Chimica e CrisDi (Centro Interdipartimentale di Cristallografia Diffrattometrica), Universita
̀
di Torino,
Via P. Giuria 7, 10125 Torino, Italy
S
* Supporting Information
ABSTRACT: An initial study has been accomplished into the synthetic feasibility of the preparation of diarylcarbenium salt via
the direct coupling of aryl (or heteroaryl) aldehydes and arenes (or heteroaryl analogues) in the presence of a strong organic
Brønsted acid. A number of stabilized aryl or heteroaryl(3-indolyl)carbenium ions, never previously prepared in the solid state,
have been isolated in excellent yields as highly stable o-benzenedisulfonimide salts and have been fully characterized. Their purity
has been proven by spectroscopic methods and chemical reduction with NaBH4. An X-ray crystal structure analysis has been
performed on one of the products: an azafulvenium species was shown to be the exclusive structure in the solid state.
tetrafluoroborates and accumulated at −78 °C before nucleophile
addition.
INTRODUCTION
■
The significance of carbocations as intermediates in organic
chemistry has long been recognized, and after initial reports
dealing with stable carbocations, namely trityl cations, several
persistent types of these species have been thoroughly studied,
normally at low temperature and in superacidic systems.1 These
cations are usually obtained in the presence of a nucleophile,
which should trap these normally unstable intermediates
immediately after their formation.
Diarylmethyl (benzhydrylium) carbocations have been the
subject of both mechanistic and preparative studies into their
use as versatile intermediates for aryl substituted compound
synthesis. Some of these are stable enough to be spectroscopi-
cally studied and have often been generated in situ via the
ionization of the corresponding benzhydryl alcohols2 or halides3 in
superacidic medium and generally at low temperature
(−70 °C). Other methods for the in situ generation of carbocations
which are useful for solvolytic studies include laser flash
induced photolysis of suitable precursors,4 and benzhydryl ester
or halide solvolysis.5 DDQ mediated oxidative reaction condi-
tions via benzylic carbon−hydrogen activation6 and oxidative
diarylmethane C−H bond dissociation using anodic oxidation
(cation pool method)7 have been used to produce in situ stabilized
benzylic carbocations, which were immediately reacted with nucleo-
philes. The latter method enables carbocations to be produced as
Their reactivity as reference electrophiles toward a variety of
nucleophiles has been investigated to a considerable extent. In
particular, extensive electrophilicity and nucleophilicity refer-
ence scales for the characterization of an high number of these
diarylmethyl cationic electrophiles and a large variety of neutral
π-, n- and σ-nucleophiles or carbanions have been reported by
Mayr et al.8 Stable symmetric and asymmetric diarylcarbenium
salts have been prepared and their reaction rates with various
nucleophiles have been studied using conventional UV−vis
spectroscopy or stopped−flow methods. Benzhydrylium ions,
in most cases symmetric, have been prepared and isolated as
tetrafluoroborates using a number of synthetic pathways: (a)
the phosphorus oxychloride promoted coupling of arenes and
carbaldehydes, followed by treatment with aqueous NaBF4 (no
reaction details reported),9a (b) the treatment of benzhydryl alcohols
with tritylium tetrafluoroborate9a or HBF4·Et2O (two examples char-
acterized)9a−c and (c) the treatment of benzhydryl ethers with
HBF4·Et2O (two examples characterized) (Scheme 1).9a,b
More often than not they have been generated in situ
generally as either tetrafluoroborates (as above) or alternatively,
as tetrachloroborates10 or triflates11 after treatment with BCl3
Received: January 25, 2012
Published: April 18, 2012
© 2012 American Chemical Society
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Scheme 1. Benzhydrylium Tetrafluoroborate Syntheses
or TMSOTf, respectively, in DCM solution at low temper-
atures from suitable starting reagents (chlorides, acetates or
OTMS derivatives). However, very few have been documented
particularly well as far as detailed reaction conditions for their
preparation and conversions, accurate spectroscopic character-
ization and other chemical properties are concerned.
Finally, mono- and dicarbenium ions stabilized by expanded
π-electron systems and possessing a 3-guaiazulenyl (or azulen-
1-yl) group have recently been synthesized in high yields via the
reaction of guaiazulene (or azulene) with aryl aldehydes
(activated benzaldehydes, five-membered heteroaryl aldehyde,
dicarbaldehydes, all-trans-retinal and trans-cinnamaldehyde) in
the presence of hexafluorophosphoric (or tetrafluoroboric) acid
in methanol (or other solvent) at 25 °C (Scheme 2). Crystal
well-established mechanism pathway, the diarylmethanol produced
in the first step dehydrates immediately to a diarylcarbenium ion,
which reacts with a second molecule of the aromatic compound
giving rise to a TRAM derivative. The synthetic procedure was
extended to the synthesis of bis- and trisindolylmethanes (3,3′-BIMs
and 3,3′,3″-TIMs) by means of an indole reaction with aryl
aldehydes or 3-formylindole, respectively, in the presence of 1 as the
catalyst.
Encouraged by the good results, we decided to study the
reaction mechanism further, with an eye to preparing, isolating
and characterizing the carbocation intermediates. From a liter-
ature survey, we found that 3-formylindole, heated in diluted
sulfuric acid, has been reported to form urorosein salt,14 which
is very stable in the presence of strong acids at pH < 1.15 The
corresponding perchlorate was isolated in high yield from 3-
formylindole and indole in hot MeOH, but no characterization
was reported.16 Some substituted phenyl(2-methyl-3H-indoly-
lidene)methanes have been prepared and isolated as hydro-
chlorides (or hydrogenosulfates) from aromatic aldehydes and
2-methylindole in HCl saturated ethanol.17 More stable
bisindolylmethylium tetrafluoroborates18a or perchlorates18b
have been prepared. The former have been synthesized by react-
ing 3-formylindole with 2-substituted indoles, while the latter
have been isolated, together with the corresponding TIMs,
from the reaction of 2-substituted indoles with 1,2-disubsti-
tuted-3-formylindoles in MeCN or from trisindolylmethane
acidic cleavage in chloroform. In fact, trisindolylmethanes are
known to be readily cleaved by acids and give rise to resonance
stabilized ammonium ions,19 while symmetric and asymmetric
TIMs have often been isolated as a mixture from the reaction of
3-formylindoles with substituted indoles in the presence of
different acid catalysts.20 Except for these few literature
reports,12,17,18 no systematic studies into the synthetic
feasibility of diarylcarbenium salt synthesis and isolation via
the direct coupling of aryl (or heteroaryl) aldehydes and arenes
(or heteroarenes) have been carried out.
Scheme 2. Syntheses of Carbenium Salts Stabilized by a
1-Azulenyl or a 3-(Guaiazulenyl) Group
structures, spectroscopic, electrochemical and chemical proper-
ties have been discussed with a view to a comparative study.12
In this article we report the full details of our studies on the
synthesis, structure characterization and stability of new non-
symmetric diarylmethylium ions isolated as stable o-benzene-
disulfonimide salts, which are ready to use and have a long shelf
life.
RESULTS AND DISCUSSION
■
In a previous paper, we reported a simple and efficient method
for the preparation of symmetric triarylmethanes (TRAMs),
from activated aryl aldehydes and activated arenes, using a
multistep Friedel−Crafts hydroxyalkylation in the presence
of catalytic amounts of a strong Brønsted acid, namely the
o-benzenedisulfonimide (1, OBS) (Scheme 3).13 Following a
Following literature suggestions, 3-formylindole (2a) was
chosen as the model aldehyde. In an initial investigation, it was
reacted with indole derivatives 3 in the presence of acid 1, in an
1.2:1:1.2 ratio in anhydrous MeCN (Scheme 4). In this reac-
tion, it was expected that o-benzenedisulfonimide would
provide a counteranion of well-known stabilizing power.21
We were aiming to isolate the intermediate salt 4, which is
highly stabilized by the resonance delocalization of the positive
charge on both indole moieties.
Scheme 3. Triarylmethane Synthesis Catalyzed by
o-Benzenedisulfonimide (1)
Initial trials to react 3-formylindole 2a and unsubstituted
indole (R = R′ = H, 3a) in the presence of 1 in MeCN
furnished tar powders as the predominant products along with
a small amount of red solid product, the ratio of which was
independent of the dilution of the reaction mixture or of the
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Scheme 4. Synthesis of o-Benzenedisulfonimide Salts 4 Starting from 3-Formylindole
reagent addition order. The black powder was probably the
acid-catalyzed polymerization product of indole moieties
through 2,3 linkages, as largely reported in literature.22
Then, 3-formylindole was reacted with 2-methylindole (R = H,
R′ = Me, 3b). Here the methyl group in 2 should prevent acid-
catalyzed polymerization. A solution of 3b in anhydrous MeCN
was added to a solution of 2a and 1 in the same solvent at room
temperature. The reaction was run with nearly equimolar amounts
of all reagents (1:1.2:1.2 molar ratio, respectively), and after
stirring for a few minutes, the separation of a brilliant red solid was
the high yield of isolated salt 4f. Accordingly, salts 4d and 4e
were isolated in significantly lower yield.
In the next phase the acid-sensitive electron-rich five-
membered heteroaryl aldehydes 2g, 2h and 2i were tested.
The (5-methyl-2-furyl), 2-thienyl and (1-methyl-2-pyrrolyl)(2-
methyl-3-indolyl)methylium salts 4g−i were obtained in good
yields (Table 1, entries 7−9). In order to prevent the acid poly-
merization of the more acid-sensitive 2-formylpyrrole (2j),
reaction conditions were slightly modified as follows: separate
solutions of 2j and 1 in anhydrous MeCN were simultaneously
dropwise added to a solution of 3b in the same solvent. Salt 4j
was obtained in a fairly lower yield (Table 1, entry 10).
The molecular structures of salts 4b−j were established in
the same way as for salt 4a. All of these isolated deeply colored
solid salts proved to be stable to air and moisture, storable at
low temperatures and ready to use.
The identity and purity of salts 4 were confirmed by means
of NaBH4 chemical reduction in anhydrous MeCN. The aryl(2-
methyl-3-indolyl)methanes 5a−j were obtained in yields
ranging from 80 to 96%. (Scheme 5; Table 2). As in the case
of the parent salt yields, reduction products including a pyrrole
moiety were obtained in modest yields (Table 2, entries 8 and 9).
The scope of carbocation synthesis by direct coupling
reaction between aldehydes and arenes was further tested by
reacting carbonyl derivatives 2a and 2b with 1,2-dimethylindole
(3c) as the nucleophile. Diarylmethylium salts 4k and 4l were
analogously isolated in high yields (Table 1, entries 11 and 12)
and their purity was proven by spectroscopic methods and by
chemical reduction to diarylmethanes 5k and 5l as described
above (Table 2, entries 11 and 12).
observed. The solid was gathered on a buchner funnel, washed
̈
with small portions of anhydrous Et2O and characterized by NMR,
mass spectrometry and elemental analysis.
Gratifyingly, (3-indolyl)(2-methyl-3-indolyl)methylium
o-benzenedisulfonimide (4a) was isolated in a 96% yield
(Table 1, entry 1). Salt 4a was further purified by means of its
recrystallization from MeCN−Et2O, and stored as a stable red
powder at low temperature for long periods without significant
loss of purity (1H and 13C NMR).
The synthetic procedure was then applied to a number of
aromatic and heteroaromatic aldehydes and activated aromatic
compounds. The structures of all tested reagents and the reac-
tion results are reported in Chart 1 and in Table 1, respectively.
The reactions of these aldehydes with 2-methylindole (3b)
gave salts containing a single indole moiety. Following the
above optimized preparative conditions, reactions of the
electron-donating group substituted benzaldehydes 2b and 2c
and 2-methylindole furnished the o-benzenedisulfonimide salts
4b and 4c which were isolated in high yields (Table 1, entries 2
and 3) and fully characterized. In general, it was necessary to
add anhydrous Et2O to complete salt precipitation.
To further extend the synthetic utility of the present method,
unsubstituted benzaldehyde (2d) and less activated 3-
methoxybenzaldeheyde (2e) were reacted with 3b: salts 4d
and 4e were obtained although in lower yield (Table 1, entries
4 and 5). Then, electron-withdrawing group substituted
aldehydes were tested, however, while salt 4f was obtained in
high yield and purity from 4-chlorobenzaldehyde (2f) (Table 1,
entry 6), the reaction of 4-nitrobenzaldehyde gave only a little
amount of black solid. Spectroscopic analyses of the isolated
solid and chromatographic analyses of the complex reaction
mixture proved that the reaction did not occur. Furthermore,
traces of the triarylmethane product were detected.
In the light of these results, we suggest that the electron-
donating substituent effect of aldehydes 2b−c strongly
stabilizes the carbenium reaction intermediates, which could
be easily isolated as o-benzenedisulfonimide salts. Starting from
4-nitrobenzaldehyde, the too unstable corresponding carboca-
tion could not be isolated, owing to the strong electron-
withdrawing substituent effect. Furthermore, its great reactivity
has been documented in TRAM synthesis from 4-nitrobenz-
aldehyde and indoles in the absence of any catalyst under
heating.13,23 In the case of 2f, the mesomeric effect of the
halogen prevailed over the inductive one as demonstrated by
In Takekuma’s papers,12 benzhydryl hexafluorophosphates
bearing a 3-guaiazulenyl group and an activated aryl or five-
membered heteroaryl group were prepared in MeOH at 25 °C.
Our efforts directed to obtain (3-guaiazulenyl)(4-methoxyphenyl)-
methylium o-benzenedisulfonimide (4m) from 2b and guaiazulene
(6) in the presence of OBS and according to our conditions in
MeCN at rt, gave the expected salt in a low 25% yield, while a
yield of 99% was obtained when the reaction was carried out in
MeOH (Scheme 6). Salt identity and purity were confirmed by
spectroscopic analyses and by reduction to diarylmethane 5m
with NaBH4 (Table 2, entry 13).
Interestingly, (4-methoxyphenyl)(2-methyl-3-indolyl)-
methylium o-benzenedisulfonimide (4b) could not be prepared
in MeOH. These results suggest that the choice of the solvent
is crucial and it must consider the nature of the involved
nucleophile; however, further studies are in progress.
OBS was easily recoverable after the workup of the aqueous
reaction mixture and it was recycled for use in other syntheses
after rapid elution on a Dowex ion−exchange resin, thus
confirming the economic and ecological advantages that have
already been reported.13
Then, the reactivity of aldehydes 2a,b,g,i with activated
aromatic nucleophiles (1,2,4-trimethoxybenzene, 2-methylfur-
an, 1-methylpyrrole and 2,5-dimethylpyrrole) was studied in
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a
Table 1. Diarylmethylium o-Benzenedisulfonimides 4a−l
a
b
Reaction conditions: 2:3:1 molar ratio =1.2:1:1.2; anhydrous MeCN, rt. Yields refer to pure solid isolated products.
the presence of OBS in the same molar ratios as above.
Unfortunately, either no reaction or very complex reaction
mixtures were obtained, although in some cases the
corresponding TRAMs were achieved in good yields under
stronger reaction conditions (see for example reaction of 2b
with 1,2,4-trimethoxybenzene or 2-methylfuran).13
In the light of these results, it can be inferred that, according
to the experimental conditions here described, one indole
moiety is needed to stabilize the secondary diarylcarbenium
ions like the guaiazulenyl group in Takekuma’s work.12
Furthermore, it should be noted that the indole ring cannot
be replaced by the pyrrole ring.
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Chart 1
Scheme 5. Reduction of Salts 4 to Diarylmethanes 5
In salts 4, the diarylcarbenium ion can be stabilized by
positive charge resonance delocalization both onto the phenyl
and the indole rings. For example, salt 4b can be described by
the more stable resonance structures I, II and III (Figure 1).
To understand the indole stabilization effect and fully char-
acterize the structure of benzhydryl cations, the X-ray analysis
of salt 4b was carried out. The molecular structure of 4b is
shown in Figure 2.
The values of bond distances clearly agree with the resonance
structure III. In fact the C(14)−N(1) (1.306(3) Å) and
C(13)−C(16) (1.357(3) Å) distances have a formal double
bond character, in particular when compared with the cor-
responding N(1)−C(7) (1.404(3) Å) and C(16)−C(17)
(1.442(3) Å) bond lengths. The presence of the positive
charge on the N(1) atom is also confirmed by the interaction
with the anion. As in other compounds, the hydrogen bond
acceptor is an oxygen atom of the anion and not the N(2)
atom. In fact the shorter hydrogen bonds involve the O(11)
and O(12) atoms and NH(1) and CH(8) atoms of the same
molecule (see Figure 2) while the other oxygen atoms and
N(2) form quite longer hydrogen bonds with different cations.
Other salts, for example [NH4][C6H4(SO2)2N]·H2O24 and the
structurally related [M][C6H4(SO2)2N]·H2O(M = K,Rb),25
show the same behavior. The hydrogen bonds are listed in
Table 3. The bond length and angle values correspond to
strong (NH(1)···O(11)) and weak (CH(8)···O(12)) character
according to the classification of Desiraju.26 N(2), O(21) and
O(22) form very weak hydrogen bonds with C−H donors and
create connections between different anions and cations. The
other distances and angles in the two ions correspond to those
reported in the literature. The anion is roughly planar with a
mean deviation from planarity of 0.053 Å. The two parts of the
cation are planar with a mean deviation from planarity of
0.021−0.039 Å and they form an angle of 31°. Two features are
noteworthy: the planarity of the Ph-O(1)C(23A, B) moiety and
the disorder of the two C(23) methyls with same occupancy
factor. The C(20)−O(1) distance of 1.352(3) Å corresponds to
a Csp2-O bond length and is quite different from the O(1)-
C(23A,B) distances (1.498(4) Å av.); the methoxy group
planarity and the bond lengths are in accord with similar
uncharged molecules. In the light of all previous results, we can
conclude that the structure of the cation salt 4b (and, in
general, of our salts) is described by the resonance structure III.
CONCLUSIONS
■
In summary, in this paper we have reported the results of a
systematic study of diarylcarbenium ion synthesis via the direct
coupling of aryl (or heteroaryl) aldehydes and arenes (or
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a
Table 2. Diarylmethanes 5a−m
a
b
Reaction conditions: NaBH4, anhydrous MeCN, rt. Yields refer to isolated products purified by column chromatography.
heteroarenes). A number of new diarylmethylium ions bearing
indole rings as the crucial framework for their stability have been
isolated as stable o-benzenedisulfonimide salts, which have long
shelf-lives and are ready to use. Preparing other diarylcarbenium
salts in the solid state is a challenging goal. To explore the synthetic
feasibility and utility of these salts as highly reactive intermediates in
organic reactions, research is currently under way on suitable
reactions with a variety of nucleophiles and reaction conditions.
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Scheme 6. Synthesis of Salt 4m
exchange resin was purchased. Room temperature (20−25 °C) is
abbreviated as rt. o-Benzenedisulfonimide (1) was prepared as
described in literature.21 Details for the reactions and yields for the
1
pure (GC, GC-MS, TLC, H NMR) isolated products are listed in
Tables 1 and 2. The structure and purity of all new products were
determined by elemental analysis, ESI, 1H, 13C NMR and DEPT
spectra. The structure and purity of known products were confirmed
Figure 1. Resonance structures for salt 4b.
1
by means of comparison of their physical and spectral data (MS, H
NMR and 13C NMR) with those reported in literature.
Crystal Analysis. The 38528 X-ray data reflections of compound
4b have been collected at rt (λ = MoKα 0.71073 Å) on a Gemini R
Ultra diffractometer.27 Crystal data: monoclinic C2/c, with a =
26.1638(12) Å, b = 13.1605(4) Å, c = 14.4032(6) Å, β = 118.224(5)°,
Z = 4, Dc = 1.424 g/cm3, μ = 0.282 mm−1, crystal size 0.036 × 0.040 ×
0.06 mm. Refinement: full-matrix least-squares on F2; non hydrogen
atoms have been anisotropically refined. The methoxy group is
disordered between two equivalent positions with 0.5 occupancy
factor. The majority of hydrogen atoms have been located in the final
Fourier-difference maps and refined with coordinates and Uiso free.
The H atoms of methyls C(23A,B) have been calculated and refined
with Uiso = 1.5 Ueq of the corresponding bonded atoms. No absorption
correction has been applied owing to the small μR. Unique data/
parameters 5642/362, GOOF = 0.821, R1 = 0.0410, wR2 = 0.0817 [I >
2σ(I)]. Software used: CrysAlisPro28 (collection, integration),
SHELXTL29 (structure solution, conventional refinement and
molecular graphics). Crystal data deposited at CSD with code
CCDC 857161.
Figure 2. Anion and cation of salt 4b [C6H4NO4S2][C17H16NO].
Relevant bond lengths (Å) with e.s.d.’s: S(1)−O(12) 1.4348(15),
S(1)−O(11) 1.4386(15), S(1)−N(2) 1.555(2), S(2)−O(21)
1.4189(17), S(2)−O(22) 1.4193(17), S(2)−N(2) 1.583(2), N(1)−
C(14) 1.306(3), N(1)−C(7) 1.404(3), C(13)−C(16) 1.358(3),
C(13)−C(14) 1.447(3), C(16)−C(17) 1.440(3). Methyls attached
to O(1) are disordered.
General Procedures. General Procedure for Diarylmethylium
o-Benzenedisulfonimides 4a−i, k−l Synthesis. A solution of the
aromatic compound 3 (3.0 mmol) in anhydrous MeCN (5 mL)
was added dropwise at rt and under stirring to a mixture of
aldehyde 2 (3.6 mmol) and o-benzenedisulfonimide (1, 0.79 g,
3.6 mmol) in anhydrous MeCN (15 mL). The deep-colored
solution lightened and a red solid separated. After stirring at rt
for 30 min, anhydrous Et2O was added to complete the
separation and the solid was gathered on a Buchner funnel,
washed with anhydrous Et2O and dried under reduced pressure.
(3-Indolyl)(2-methyl-3-indolyl)methylium o-Benzenedisulfoni-
mide (4a). (1.37 g, 96% yield); dp 198.5−199.5 °C (anhydrous
MeCN/anhydrous Et2O); 1H NMR (200 MHz, CDCl3−CF3COOD):
δ = 2.83 (s, 3H), 7.31−7.49 (m, 5H), 7.54−7.69 (m, 2H), 7.84−7.98
(m, 5H), 8.65 (s, 1H), 8.68 (s, 1H); 13C NMR (50 MHz, CDCl3−
CF3COOD): δ = 12.9, 113.8, 120.1 (q), 120.7, 121.8, 121.8 (2C),
124.2 (q), 125.0, 126.2, 126.2, 126.5, 127.4, 134.3 (2C), 137.3 (q),
138.1 (q), 139.2 (q, 3C), 141.3, 147.4, 162.6 (q); IR (CHCl3) νmax
3024, 3020, 2380, 1520, 1431, 1235, 1220, 1200; exact ESI full mass:
Table 3. Most Relevant Hydrogen Bonds in Salt 4b
D−H···A
D−H (Å) H···A (Å) D···A(Å)
D−H···A
(deg)
N(1)−H(1)···O(11)
C(8)−H(8)···O(12)
0.79(2)
0.90(2)
2.08(2)
2.42(2)
2.842(3)
3.224(3)
165(2)
150(1)
EXPERIMENTAL SECTION
■
General Information. All the reactions were conducted in vials
using analytical grade reagents, and were monitored by TLC, GC, GC-
MS and NMR spectrometry. GC-MS spectra were recorded on a mass
selective detector connected to a GC with a cross-linked methyl
silicone capillary column. Mass spectra were recorded on a mass
spectrometer equipped with ElectroSpray Ionization source (ESI).
Infrared (IR) data are presented as frequency of absorption (cm−1).
1H NMR and 13C NMR spectra were recorded in CDCl3 or CDCl3−
CF3COOD on a spectrometer at 200 and 50 MHz, respectively;
chemical shifts are given in ppm relative to CDCl3. TLC were
performed on silica gel TLCPET foils GF 254, 2−25 μm, layer
thickness 0.2 mm, medium pore diameter 60 Å. Plates were visualized
using UV light (254 nm). Column chromatography was carried out
using SiO2 (pore size 70 Å, 70−230 mesh). Petroleum ether refers to
the fraction boiling in the range 40−60 °C and is abbreviated as PE.
Commercially available reagents and solvents were used without
purification or distillation prior to use. DOWEX HCR-W2 ion-
+
found m/z 259.24 (calcd for C18H15N2 : m/z 259.12); Anal. Calcd for
C24H19N3O4S2: C, 60.36; H, 4.01; N, 8.80; S, 13.43; Found C, 60.32;
H, 4.00; N, 8.78; S, 13.39.
(4-Methoxyphenyl)(2-methyl-3-indolyl)methylium o-Benzenedi-
sulfonimide (4b). (1.26 g, 90% yield); dp 152.0−153.0 °C (anhydrous
MeCN/anhydrous Et2O); 1H NMR (200 MHz, CDCl3−CF3COOD):
δ = 2.89 (s, 3H), 3.96 (s, 3H), 7.11 (d, J = 9.0 Hz, 2H), 7.32−7.55 (2
overlapped m, 3H), 7.77−7.85 (m, 2H), 7.87−7.95 (m, 2H), 8.00 (d,
J = 9.0 Hz, 2H), 8.12 (d, J = 7.0 Hz, 1H), 8.37 (s, 1H); 13C NMR (50
MHz, CDCl3−CF3COOD): δ = 13.5, 55.9, 115.2, 115.4 (2C), 121.9
(2C), 122.3, 123.9 (q), 125.5 (q), 127.6 (q), 127.9, 129.8, 134.5 (2C),
136.3 (2C), 139.0 (q, 2C), 139.7 (q), 157.7, 166.2 (q), 170.1 (q); IR
(CHCl3) νmax 3026, 3018, 2400, 1522, 1430, 1230, 1190; exact ESI full
mass: found m/z 250.22 (calcd for C17H16NO+, m/z 250.12); Anal.
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Calcd for C23H20N2O5S2: C, 58.96; H, 4.30; N, 5.98; S 13.69. Found
C, 58.90; H, 4.32; N, 5.94; S, 13.70.
2390, 1520, 1420, 1235, 1200; exact ESI full mass: found m/z 226.18
(calcd for C14H12NS: M+, m/z 226.06); Anal. Calcd for
C20H16N2O4S3: C, 54.04; H, 3.63; N, 6.30; S, 21.64. Found C,
53.96; H, 3.61; N, 6.38; S, 21.55.
(4-Hydroxyphenyl)(2-methyl-3-indolyl)methylium o-Benzenedi-
sulfonimide (4c). (1.24 g, 91% yield); dp 173.1−174.0 °C (anhydrous
MeCN/anhydrous Et2O); 1H NMR (200 MHz, CDCl3−CF3COOD):
δ = 2.87 (s, 3H), 7.05 (d, J = 8.8 Hz, 2H), 7.39−7.49 (m, 3H), 7.81−
7.96 (m, 6H), 8.09 (d, J = 6.6 Hz, 1H), 8.32 (br s, 1H); 13C NMR
(50 MHz, CDCl3−CF3COOD): δ = 13.3, 114.9, 117.1 (2C), 121.8
(2C), 122.4, 123.9 (q), 125.4 (q), 127.1 (q), 127.9, 129.6, 134.3 (2C),
136.8 (2C), 139.2 (q), 139.5 (q), 158.1, 163.7 (q), 169.7 (q); IR
(CHCl3) νmax 3028, 3018, 2400, 1510, 1430, 1215, 1200; exact ESI full
mass: found m/z 236.26 (calcd for C16H14NO: M+, m/z 236.11); Anal.
Calcd for C22H18N2O5S2: C, 58.14; H, 3.99; N, 6.16; S, 14.11. Found
C, 58.20; H, 3.90; N, 6.20; S, 14.00.
(2-Methyl-3-indolyl)(1-methyl-2-pyrrolyl)methylium o-Benzene-
disulfonimide (4i). (1.24 g, 94% yield); dp 146.4−148.0 °C
(anhydrous MeCN/anhydrous Et2O); 1H NMR (200 MHz,
CDCl3−CF3COOD): δ = 2.80 (s, 3H), 3.95 (s, 3H), 6.66 (dd, J =
4.8 and J = 2.2 Hz, 1H), 7.31−7.40 (m, 2H), 7.42−7.52 (m, 2H),
7.74−7.83 (m, 2H), 7.84−7.94 (m, 3H), 8.04 (br s, 1H), 8.14−8.22
(m, 1H); 13C NMR (50 MHz, CDCl3−CF3COOD): δ = 12.9, 34.8,
114.1, 116.3, 119.9 (q), 121.0, 121.8 (2C), 124.1 (q), 126.4, 127.9,
128.5, 131.7 (q), 134.3 (2C), 138.2, 138.5 (q), 139.1 (q, 2C), 141.2
(q); IR (CHCl3) νmax 3026, 3018, 2360, 1530, 1427, 1225, 1210, 1200;
exact ESI full mass: found m/z 223.19 (calcd for C15H15N2: M+, m/z
223.12); Anal. Calcd for C21H19N3O4S2: C, 57.13; H, 4.34; N, 9.52; S,
14.52. Found C, 57.18; H, 4.31; N, 9.50; S, 14.47.
(2-Methyl-3-indolyl)(phenyl)methylium o-Benzenedisulfonimide
(4d). (0.62 g, 47% yield); dp 143.5−145.0 °C (anhydrous MeCN/
1
anhydrous Et2O); H NMR (200 MHz, CDCl3−CF3COOD): δ =
3.00 (s, 3H), 7.32−7.72 (m, 6H), 7.79−7.95 (m, 6H), 8.05 (d, J = 7.8
Hz, 1H), 8.47 (br s, 1H); 13C NMR (50 MHz, CDCl3−CF3COOD):
δ = 13.6, 115.5, 122.0 (2C), 123.1, 123.7 (q), 128.6, 129.4 (2C), 130.8,
131.2 (q), 131.7 (2C), 132.3 (q), 134.5 (2C), 134.8, 138.8 (q, 2C),
140.1 (q), 157.7, 172.6 (q); IR (CHCl3) νmax 3028, 3018, 2405, 1521,
1423, 1231; exact ESI full mass: found m/z 220.24 (calcd for C16H14N:
M+, m/z 220.11); Anal. Calcd for C22H18N2O4S2: C, 60.26; H, 4.14; N,
6.39; S, 14.62. Found C, 60.10; H, 3.98; N, 6.25; S, 14.50.
(2-Methyl-3-indolyl)(2-pyrrolyl)methylium o-Benzenedisulfoni-
mide (4j). A solution of the aromatic compound 3b (0.39 g;
3.0 mmol) in MeCN (10 mL) and a solution of o-benzenedisulfonimide
(1, 0.79 g, 3.6 mmol) in MeCN (10 mL) were simultaneously added
dropwise to a solution of the aldehyde 2g (0.34; 3.6 mmol) in MeCN
(10 mL) at rt and under stirring. The solution was deeply red colored
and a black powder began to separate. After stirring at rt for 30 min,
the solid was filtered off. Anhydrous Et2O (75 mL) was added to the
solution to precipitate the brown solid which was gathered on a
Buchner funnel, washed thoroughly with anhydrous Et2O and dried
under reduced pressure; (0.86 g, 67% yield); dp 166.7−167.8 °C
(3-Methoxyphenyl)(2-methyl-3-indolyl)methylium o-Benzenedi-
sulfonimide (4e). (0.73 g, 52% yield); dp 134.5−136.20 °C
(anhydrous MeCN/anhydrous Et2O); 1H NMR (200 MHz,
CDCl3−CF3COOD): δ = 2.96 (s, 3H), 3.92 (s, 3H), 7.20−7.33 (m,
1H), 7.38−7.58 (m, 6H), 7.83−7.98 (m, 4H), 8.06 (d, J = 7.8 Hz,
1H), 8.44 (s, 1H); 13C NMR (50 MHz, CDCl3−CF3COOD): δ =
13.2, 55.4, 115.3, 116.3, 120.7, 122.1 (2C), 123.4, 123.6 (q), 124.8,
128.7, 130.7, 130.9, 131.5 (q), 133.6 (q), 134.9 (2C), 138.2 (q, 2C),
157.4, 159.3(q), 172.7 (q); IR (CHCl3) νmax 3023, 3016, 2400, 1521,
1421, 1216; exact ESI full mass: found m/z 250.20 (calcd for
C17H16NO+, m/z 250.12); Anal. Calcd for C23H20N2O5S2: C, 58.96;
H, 4.30; N, 5.98; S 13.69. Found C, 58.86; H, 4.20; N, 5.90; S, 13.76.
(4-Chlorophenyl)(2-methyl-3-indolyl)methylium o-Benzenedisul-
fonimide (4f). (1.33 g, 94% yield); dp 180.6−181.5 °C (anhydrous
MeCN/anhydrous Et2O); 1H NMR (200 MHz, CDCl3−CF3COOD):
δ = 2.95 (s, 3H), 7.33−7.61 (m, 5H), 7.80−8.05 (m, 7H), 8.43 (s,
1H); 13C NMR (50 MHz, CDCl3−CF3COOD): δ = 13.5, 115.5, 122.0
(2C), 123.1, 123.5 (q), 128.8, 129.9 (2C), 130.6 (q), 130.9, 131.4 (q),
132.8 (2C), 134.7 (2C), 138.6 (q), 140.1 (q), 141.6 (q), 155.9, 172.8
(q); IR (CHCl3) νmax 3023, 3018, 2400, 1521, 1424, 1216; exact ESI
full mass: found m/z 254.19 (calcd for C16H13ClN+: M+, m/z 254.07);
Anal. Calcd for C22H17ClN2O4S2: C, 58.87; H, 3.62; Cl, 7.50; N, 5.92;
S, 13.56. Found C, 58.62; H, 3.60; Cl, 7.37; N, 6.00; S, 13.42.
(5-Methyl-2-furyl)(2-methyl-3-indolyl)methylium o-Benzenedisul-
fonimide (4g). (1.29 g, 97% yield); dp 172−174 °C (anhydrous
MeCN/anhydrous Et2O); 1H NMR (200 MHz, CDCl3−CF3COOD):
δ = 2.72 (s, 3H), 2.84 (s, 3H), 6.67 (d, J = 3.8 Hz, 1H), 7.43−7.52 (m,
3H), 7.65 (d, J = 3.8, 1H), 7.80 (s, 1H), 7.84−7.99 (m, 4H), 8.58−
8.66 (m, 1H); 13C NMR (50 MHz, CDCl3−CF3COOD): δ = 13.1,
15.0, 114.4, 115.2, 121.9 (2C), 122.2 (q), 123.9 (q), 124.5, 127.4,
128.9, 134.1, 134.3 (2C), 137.1, 138.9 (q), 139.1 (q, 2C), 149.8 (q),
168.2 (q), 168.9 (q); IR (CHCl3) νmax 3027, 3020, 2390, 1515, 1435,
1235, 1205; exact ESI full mass: found m/z 224.17 (calcd for
C15H14NO: M+, m/z 224.11); Anal. Calcd for C21H18N2O5S2: C,
57.00; H, 4.10; N, 6.33; S, 14.49. Found C, 56.88; H, 4.18; N, 6.38; S,
14.41.
1
(anhydrous MeCN/anhydrous Et2O); H NMR (200 MHz, CDCl3−
CF3COOD): δ = 2.70 (s, 3H), 6.68−6.73 (m, 1H), 7.28−7.44 (m,
3H), 7.67−7.72 (m, 2H), 7.73−7.81 (m, 2H), 7.82−7.93 (m, 2H),
8.00−8.06 (m, 1H), 8.17 (br s, 1H); 13C NMR (50 MHz, CDCl3−
CF3COOD): δ = 12.9, 114.0, 118.0, 119.3 (q), 120.9, 121.8 (2C),
123.9 (q), 126.3, 127.6, 129.0, 130.8 (q, 2C), 134.2 (2C), 137.8, 138.2
(q), 139.2 (q, 2C), 141.1; IR (CHCl3) νmax 3026, 3018, 2415, 1515,
1425, 1225, 1211, 1200; exact ESI full mass: found m/z 209.20 (calcd
for C14H13N2: M+, m/z 209.11); Anal. Calcd for C20H17N3O4S2: C,
56.19; H, 4.01; N, 9.83; S, 15.00. Found C, 56.10; H, 3.95; N, 10.05; S,
14.90.
(1,2-Dimethyl-3-indolyl)(3-indolyl)methylium o-Benzenedisulfo-
nimide (4k). (1.42 g, 96% yield); dp 194.4−195.5 °C (anhydrous
MeCN/anhydrous Et2O); 1H NMR (200 MHz, CDCl3−CF3COOD):
δ = 2.80 (s, 3H), 3.87 (s, 3H), 7.30−7.46 (m, 5H), 7.49−7.66 (m,
2H), 7.69−7.77 (m, 2H), 7.79−7.90 (m, 3H), 8.68 (s, 1H), 8.71 (s,
1H); 13C NMR (50 MHz, CDCl3−CF3COOD): δ = 11.9, 31.8, 111.6,
114.2, 117.5 (q), 120.1 (q), 120.6, 121.7 (2C), 122.3, 124.3 (q), 124.9,
126.2 (2C), 126.5, 127.2, 134.0 (2C), 137.7 (q), 139.5 (q, 2C), 140.2
(q, 2C), 147.6, 161.1 (q); IR (CHCl3) νmax 3027, 3018, 2392, 1535,
1435, 1227, 1210, 1200; exact ESI full mass: found m/z 273.28 (calcd
for C19H17N2: M+, m/z 273.14); Anal. Calcd for C25H21N3O4S2: C,
61.08; H, 4.31; N, 8.55; S, 13.05. Found C, 60.99; H, 4.31; N, 8.53; S,
13.11.
(1,2-Dimethyl-3-indolyl)(4-methoxyphenyl)methylium o-Benze-
nedisulfonimide (4l). (1.32 g, 91% yield); dp 153.1−154.2 °C
1
(anhydrous MeCN/anhydrous Et2O); H NMR (200 MHz, CDCl3−
CF3COOD): δ = 2.89 (s, 3H), 3.94 (s, 3H), 3.95 (s, 3H), 7.08 (d, J =
9.0 Hz, 2H), 7.38−7.49 (m, 1H), 7.49−7.56 (m, 2H), 7.72−7.79 (m,
2H), 7.80−7.88 (m, 2H), 7.97 (d, J = 9.0 Hz, 2H), 8.15 (d, J = 7.60
Hz, 1H), 8.46 (s, 1H); 13C NMR (50 MHz, CDCl3−CF3COOD): δ =
12.3, 32.9, 55.9, 113.0, 115.4 (2C), 121.9 (2C), 122.6, 124.0 (q), 125.6
(q), 127.2 (q), 128.4, 129.7, 134.3 (2C), 136.4 (2C), 139.0 (q), 142.0
(q), 157.6, 166.2 (q), 170.0 (q); IR (CHCl3) νmax 3028, 3019, 2410,
1533, 1423, 1235, 1198; exact ESI full mass: found m/z 264.25 (calcd
for C18H18NO: M+, m/z 264.14); Anal. Calcd for C24H22N2O5S2: C,
59.73; H, 4.60; N, 5.81; S, 13.29. Found C, 59.71; H, 4.61; N, 5.83; S,
13.19.
(2-Methyl-3-indolyl)(2-thienyl)methylium o-Benzenedisulfoni-
mide (4h). (1.24 g, 95% yield); dp 159−160 °C (anhydrous
MeCN/anhydrous Et2O); 1H NMR (200 MHz, CDCl3−CF3COOD):
δ = 2.93 (s, 3H), 7.41−7.58 (m, 4H), 7.76−7.84 (m, 2H), 7.88−7.94
(m, 2H), 8.08 (d, J = 4.0 Hz, 1H), 8.22 (d, J = 5.0 Hz, 1H), 8.46 (s,
1H) overlapped with 8.48−8.56 (m, 1H); 13C NMR (50 MHz,
CDCl3−CF3COOD): δ = 13.6, 115.3, 121.9 (2C), 123.0 (q), 123.4,
125.9 (q), 128.0, 129.9, 130.5, 134.4 (2C), 137.0 (q), 139.0 (q, 2C),
139.3 (q), 142.7, 145.0, 146.3, 170.9 (q); IR (CHCl3) νmax 3021, 3015,
(3-Guaiazulenyl)(4-methoxyphenyl)methylium o-Benzenedisul-
fonimide (4m). A solution of the compound 6 (0.20 g; 1.0 mmol)
in MeOH (3 mL) was added dropwise at rt and under stirring to a
mixture of aldehyde 2b (0.16 g; 1.2 mmol) and o-benzenedisulfonimide
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(1, 0.26 g, 1.2 mmol) in MeOH (3 mL). The solution was deeply red
colored. After stirring at rt for 120 min, anhydrous Et2O was added to
complete the separation and the red solid was gathered on a Buchner
funnel, washed thoroughly with anhydrous Et2O and dried under
reduced pressure; (0.53 g, 99% yield); dp 151.4−152.3 °C (anhydrous
MeCN/anhydrous Et2O); 1H NMR (200 MHz, CDCl3−CF3COOD):
δ = 1.42 (d, J = 7.0 Hz, 6H), 2.50 (s, 3H), 3.32 (s, 3H) overlapped
with 3.30−3.45 (m, 1H), 3.91 (s, 3H), 7.08 (d, J = 8.8 Hz, 2H), 7.74
(d, J = 9.0 Hz, 2H), 7.77−7.85 (m, 2H), 7.86−7.98 (2 m overlapped,
3H), 8.21 (dd, J = 11.2 and 2.0 Hz, 1H), 8.35 (d, J = 11.0 Hz, 1H),
8.43 (d, J = 2.0 Hz, 1H), 8.66 (s, 1H); 13C NMR (50 MHz, CDCl3−
CF3COOD): δ = 13.2, 23.4 (2C), 29.2, 39.4, 55.7, 109.0 (q), 115.6
(2C), 121.9 (2C), 127.7 (q), 134.3 (2C), 136.0, 136.4 (q), 137.5,
139.1 (q, 2C), 141.3, 143.0 (2C), 147.7, 150.9, 152.2 (q), 155.3 (q),
158.6 (q), 164.4 (q), 168.3 (q); IR (CHCl3) νmax 3025, 3016, 2405,
1531, 1425, 1235, 1227, 1205, 1200; exact ESI full mass: found m/z
317.22 (calcd for C23H25O: M+, m/z 317.19); Anal. Calcd for
C29H29NO5S2: C, 65.02; H, 5.46; N, 2.61; S, 11.97. Found C, 65.05; H,
5.49; N, 2.58; S, 11.90.
110.6, 114.2, 118.2, 119.1, 120.6, 120.8, 128.7 (q), 129.1, 131.5 (q),
135.1 (q), 143.3 (q), 159.5 (q); MS m/z (%): 251 [M+] (100), 236
(45), 144 (85).
(4-Chlorophenyl)(2-methyl-3-indolyl)methane (5f). Chromato-
graphic eluent: PE−AcOEt 8:2; white solid (0.23 g, 90% yield); mp
133.5−134.5 °C (DCM−PE); 1H NMR (200 MHz, CDCl3): δ = 2.32
(s, 3H), 3.98 (s, 2H), 6.94−7.38 (m,8H), 7.72 (br s, 1H); 13C NMR
(50 MHz, CDCl3): δ = 11.6, 29.3, 109.9(q), 110.0, 118.0, 119.2, 121.0,
128.2 (2C), 128.5 (q), 129.4 (2C), 131.1 (q), 131.5 (q), 135.1 (q),
139.9 (q); MS m/z (%): 255 [M+] (95), 240 (50), 144 (100); Anal.
Calcd for C16H13ClN: C, 75.44; H, 5.14; Cl, 13.92; N, 5.50. Found: C,
75.55; H, 5.25; Cl, 13.80; N, 5.42.
(5-Methyl-2-furyl)(2-methyl-3-indolyl)methane (5g). Chromato-
1
graphic eluent: PE−AcOEt 8:2; viscous oil (0.22 g, 91% yield); H
NMR (200 MHz, CDCl3): δ = 2.27 (s, 3H), 2.31 (s, 3H), 4.04 (s,
2H), 5.78−5.88 (m, 2H), 7.10−7.20 (m, 3H), 7.45−7.58 (2 m
overlapped, 2H); 13C NMR (50 MHz, CDCl3): δ = 11.4, 13.5, 23.2,
105.9 (2C), 107.7 (q), 110.2, 118.2 119.1, 120.8, 128.5 (q), 131.8 (q),
135.1 (q), 150.3 (q), 153.1 (q); MS m/z (%): 225 [M+] (95), 210
(100), 182 (40); Anal. Calcd for C15H15NO: C, 79.97; H, 6.71; N,
6.22. Found: C, 79.77; H, 6.70; N, 6.40.
General Procedure for Diarylmethylium o-Benzenedisulfoni-
mides 4a−m Reduction. NaBH4 (2.0 mmol, 0.08 g) was added
portionwise at rt and under stirring to a solution of the salts 4 (1.0 mmol)
in anhydrous MeCN (15 mL). The reaction was instantaneous and
the deep colored solution immediately faded. After stirring at rt for
10 min, the reaction mixture was treated with Et2O/water (40 mL;
1:1). The organic phase was separated, washed with brine (2 × 20 mL)
and evaporated under reduced pressure. The crude residue was the
(2-Methyl-3-indolyl)(2-thienyl)methane (5h). Chromatographic
eluent: PE−AcOEt 7:3; white solid (0.20 g, 88% yield); mp 69.4−
70.2 °C (DCM−PE); 1H NMR (200 MHz, CDCl3): δ = 2.35 (s, 3H),
4.22 (s, 2H), 6.75−6.82 (m, 1H), 6.82−6.90 (m, 1H), 7.03−7.15 (m,
3H), 7.18−7.28 (m, 1H), 7.42−7.48 (m, 1H), 7.65 (br s, 1H); 13C
NMR (50 MHz, CDCl3): δ = 11.5, 24.5, 110.3 (2C, CH and q
overlapped), 118.1, 119.3, 121.0, 123.1, 124.0, 126.7, 128.3 (q), 131.6
(q), 135.1 (q), 145.5 (q); MS m/z (%): 227 [M+] (100), 212 (80),
144 (45); Anal. Calcd for C14H13NS: C, 73.97; H, 5.76; N, 6.16; S,
14.11. Found: C, 73.79; H, 5.60; N, 6.20; S, 14.00.
1
virtually pure reduction product 5 (GC, GC−MS, H NMR). The
eluent of the short column chromatography purification, isolated
product yields and physical and spectroscopic data are listed below.
(3-Indolyl)(2-methyl-3-indolyl)methane (5a).30 Chromatographic
eluent: PE−AcOEt 7:3; white solid (0.24 g, 93% yield); mp 172.2−
173 °C (DCM−PE) (lit. mp 131−134 °C);30 1H NMR (200 MHz,
CDCl3): δ = 2.32 (s, 3H), 4.12 (s, 2H), 6.61 (br s, 1H), 6.95−7.30 (m,
7H), 7.43 (d, J = 7.4 Hz, 1H), 7.56−7.72 (m, 2H); 13C NMR
(50 MHz, CDCl3): δ = 11.6, 19.8, 109.9, 110.2 (q), 110.9, 116.0,
118.4, 118.7, 118.9, 119.0, 120.7, 121.7, 121.9 (q), 127.3 (q), 128.8
(q), 131.1 (q), 135.1 (q), 136.3 (q); MS m/z (%): 260 [M+](100),
245 (55), 143 (45).
(2-Methyl-3-indolyl)(1-methyl-2-pyrrolyl)methane (5i). Chro-
matographic eluent: PE−AcOEt 7:3; white solid (0.15 g, 68% yield);
1
mp 106.6−107.6 °C (DCM−PE); H NMR (200 MHz, CDCl3): δ =
2.25 (s, 3H), 3.44 (s, 3H), 3.93 (s, 2H), 5.74−5.80 (m, 1H), 5.96 (dd,
J = 3.4 and J = 2.8 Hz, 1H), 6.47−6.52 (m, 1H), 6.94−7.10 (m, 2H),
7.17−7.25 (m, 1H), 7.27−7.35 (m, 1H), 7.68 (br s, 1H); 13C NMR
(50 MHz, CDCl3): δ = 11.5, 22.0, 33.6, 106.3, 107.2, 108.4 (q), 110.0,
118.3, 119.1, 120.8, 121.2, 128.6 (q), 131.4 (q), 131.7 (q), 135.1 (q);
MS m/z (%): 224 [M+] (100), 209 (45), 143 (90); Anal. Calcd for
C15H16N2: C, 80.32; H, 7.19; N, 12.49. Found: C, 80.19; H, 7.00; N,
12.26.
(4-Methoxyphenyl)(2-methyl-3-indolyl)methane (5b).31 Chroma-
tographic eluent: PE−AcOEt 7:3; white solid (0.23 g, 93% yield); mp
116.6−117.8 °C (DCM−PE) (lit. mp 119−120 °C);17b 1H NMR
(200 MHz, CDCl3): δ = 2.45 (s, 3H), 3.92 (s, 3H), 4.32 (s, 2H), 7.08
(d, J = 8.6 Hz, 2H), 7.35−7.50 (m, 5H), 7.67 (br s, 1H), 7.72−7.85
(m, 1H); 13C NMR (50 MHz, CDCl3): δ = 11.6, 29.4, 55.3, 110.7 (q),
110.8, 114.0 (2C), 118.6, 119.4, 121.1, 129.1 (q), 129.5 (2C), 132.0
(q), 134.2 (q), 135.6 (q), 157.8 (q); MS m/z (%): 251 [M+] (100),
236 (75), 144 (70).
(2-Methyl-3-indolyl)(2-pyrrolyl)methane (5j). Chromatographic
eluent: PE−AcOEt 7:3; viscous oil (0.14 g, 67% yield); 1H NMR
(200 MHz, CDCl3): δ = 2.29 (s, 3H), 4.02 (s, 2H), 5.96−6.01 (m,
1H), 6.05−6.12 (m, 1H), 6.49−6.53 (m, 1H), 6.95−7.13 (m, 2H),
7.17−7.27 (m, 1H), 7.31−7.39 (m, 1H), 7.75 (br s, 2H); 13C NMR
(50 MHz, CDCl3): δ = 11.3, 22.3, 105.0, 108.1, 108.4 (q), 110.2,
116.1, 118.0, 119.4, 121.0, 128.6 (q), 131.2 (q), 131.9 (q), 135.1 (q);
MS m/z (%): 210 [M+] (100), 195 (45), 131 (55); Anal. Calcd for
C14H14N2: C, 79.97; H, 6.71; N, 13.32. Found: C, 80.10; H, 6.60; N,
13.24.
(4-Hydroxyphenyl)(2-methyl-3-indolyl)methane (5c).32 Chroma-
tographic eluent: PE−AcOEt 7:3; white solid (0.21 g, 90% yield); mp
141.8−142.6 °C (DCM−PE); 1H NMR (200 MHz, CDCl3): δ = 2.30
(s, 3H), 3.94 (s, 2H), 6.62 (d, J = 8.4 Hz, 2H), 6.90−7.12 (m, 5H),
7.80−7.25 (m, 1H), 7.30−7.38 (m,1H), 7.73 (br s, 1H); 13C NMR
(50 MHz, CDCl3): δ = 11.6, 29.0, 110.0, 110.7 (q), 115.0 (2C), 118.2,
119.0, 120.8, 128.7 (q), 129.1 (2C), 131.4 (q), 133.6 (q), 135.1 (q),
153.4 (q); MS m/z (%): 237 [M+] (100), 222 (70), 144 (85).
(2-Methyl-3-indolyl)phenylmethane (5d).31 Chromatographic elu-
ent: PE−AcOEt 8:2; white solid (0.22 g, quant. yield); mp 118.5−
119.2 °C (DCM−PE) (lit. mp 122−123 °C);33 1H NMR (200 MHz,
CDCl3): δ = 2.33 (s, 3H), 4.03 (s, 2H), 6.94−7.25 (m, 8H), 7.35 (d,
J = 7.6 Hz, 1H), 7.73 (br s, 1H); 13C NMR (50 MHz, CDCl3): δ =
11.6, 29.9, 109.9, 110.4 (q), 118.2, 119.1, 120.8, 125.4, 128.1 (4C),
128.7 (q), 131.4 (q), 135.1 (q), 141.5 (q); MS m/z (%): 221 [M+]
(100), 206 (45), 144 (90).
(1,2-Dimethyl-3-indolyl)(3-indolyl)methane (5k).18a Chromato-
graphic eluent: PE−AcOEt 7:3; white solid (0.24 g, 86% yield); mp
139.6−141.2 °C (DCM−PE); 1H NMR (200 MHz, CDCl3): δ = 2.35
(s, 3H), 3.64 (s, 3H), 4.15 (s, 2H), 6.60−6.64 (m, 1H), 6.93−7.06 (m,
1H), 7.07−7.18 (m, 2H), 7.19−7.28 (m, 2H), 7.46 (d, J = 7.8 Hz,
1H), 7.62−7.69 (m, 2H); 13C NMR (50 MHz, CDCl3): δ = 10.2, 20.1,
29.4, 108.4, 109.4 (q), 110.9, 116.3 (q), 118.4, 118.4, 118.7, 119.0,
120.3, 121.7, 122.0, 127.3 (q), 127.9 (q), 133.1 (q), 136.4 (q), 136.5
(q); MS m/z (%): 274 [M+] (100), 259 (80), 157 (30).
(4-Methoxyphenyl)(1,2-dimethyl-3-indolyl)methane (5l). Chro-
matographic eluent: PE−AcOEt 7:3; white solid (0.25 g, 94% yield);
1
mp 94.4−95.5 °C (PE); H NMR (200 MHz, CDCl3): δ = 2.34 (s,
(3-Methoxyphenyl)(2-methyl-3-indolyl)methane (5e).31 Chroma-
tographic eluent: PE−AcOEt 7:2; white solid (0.20 g, 80% yield); mp
87.5−88.2 °C (DCM−PE) (lit. mp 84−87 °C);31 1H NMR (200
MHz, CDCl3): δ = 2.32 (s, 3H), 3.72 (s, 3H), 4.02 (s, 2H), 6.65−6.85
(m, 3H), 6.98−7.26 (m, 4H), 7.40 (d, J = 8.2 Hz, 1H), 7.68 (br s, 1H);
13C NMR (50 MHz, CDCl3): δ = 11.6, 30.0, 54.9, 110.0, 110.2 (q),
3H), 3.63 (s, 3H), 3.72 (s, 3H), 4.01 (s, 2H), 6.74 (d, J = 8.6 Hz, 2H),
7.10 (d, J = 8.6 Hz, 2H) overlapped with 6.93−7.16 (m, 2H), 7.22 (d,
J = 7.6 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H); 13C NMR (50 MHz,
CDCl3): δ = 10.3, 29.4, 55.1, 108.4, 110.1 (q), 113.6 (2C), 118.2,
118.7, 120.4, 127.9 (q), 129.0 (2C), 133.3 (q), 134.0 (q), 136.6 (q),
157.6 (q); MS m/z (%): 265 [M+] (100), 250 (95), 158 (75); Anal.
4286
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The Journal of Organic Chemistry
Article
Calcd for C18H19NO: C, 81.47; H, 7.22; N, 5.28. Found: C, 81.33; H,
7.20; N, 5.39.
(13) Barbero, M.; Cadamuro, S.; Dughera, S.; Magistris, C.;
Venturello, P. Org. Biomol. Chem. 2011, 8393.
(3-Guaiazulenyl)(4-methoxyphenyl)methane (5m).12 Chromato-
graphic eluent: PE−AcOEt 8:2; blue paste (0.31 g, 96% yield);12 1H
NMR (200 MHz, CDCl3): δ = 1.32 (d, J = 7.2 Hz, 6H), 2.60 (s, 3H),
2.83 (s, 3H), 3.00 (sept, J = 6.8 Hz, 1H), 3.73 (s, 3H), 4.52 (s, 2H),
6.77 (d, J = 8.8 Hz, 2H overlapped with m, 1H), 6.94 (d, J = 8.8 Hz,
2H), 7.23 (dd, J = 11.4 and 2.0 Hz, 1H), 7.36 (s, 1H), 8.06 (d, J =
2.0 Hz, 1H); 13C NMR (50 MHz, CDCl3): δ = 12.8, 24.5, 26.5,
36.2, 37.6, 55.1, 113.6 (2C), 124.0 (q), 125.9 (q), 126.1, 129.3 (2C),
132.9 (q), 133.2, 134.6, 135.3 (q), 137.6 (q), 138.7 (q), 141.0, 145.3 (q),
157.5 (q); MS m/z (%): 318 [M+] (100), 303 (95).
(14) Harley-Mason, J.; Bullock, J. D. Biochem. J. 1952, 51, 430.
(15) Korolev, A. M.; Yudina, L. N.; Lazhko, E. I.; Reznikova, M. I.;
Preobrazhenskaya, M. N. Chem. Heterocycl. Compd. 1999, 35, 561.
(16) Smith, G. F. J. Chem. Soc. 1954, 3842.
(17) (a) Burr, G. O.; Gortner, R. A. J. Am. Chem. Soc. 1924, 46, 1224.
(b) Schellenberg, K. A.; McLean, G. W.; Lipton, H. L.; Lietman, P. S. J.
Am. Chem. Soc. 1967, 89, 1948.
(18) (a) Jackson, A. H.; Prasitpan, N.; Shannon, V. R.; Tinker, A. C.
J. Chem. Soc., Perkin Trans. I 1987, 2543. (b) Berti, C.; Greci, L.;
Marchetti, L. J. Heterocycl. Chem. 1978, 15, 433.
(19) Shiri, M.; Zolfigol, M. A.; Kruger, H. G.; Tanbakouchian, Z.
Chem. Rev. 2010, 110, 2250 and references therein.
ASSOCIATED CONTENT
■
(20) For examples see: (a) Hazra, A.; Paira, P.; Sahu, K. B.; Banerjee,
S.; Mondal, N. B. Catal. Commun. 2008, 9, 1681. (b) Naskar, S.; Hazra,
A.; Paira, P.; Sahu, K. B.; Banerjee, S.; Mondal, N. B. J. Chem. Res.
2008, 568. (c) Chakrabarty, M.; Sarkar, S. Tetrahedron Lett. 2002, 43,
1351. (d) Lavrenov, S. N.; Luzikov, Y. N.; Bykov, E. E.; Reznikova, M.
I.; Stepanova, E. V.; Glazunova, V. A.; Volodina, Y. L.; Tatarsky, V. V.;
Shtil, A. A.; Preobrazhenskaya, M. N. Org. Biomol. Chem. 2010, 18,
6905.
S
* Supporting Information
1H and 13C NMR spectra for compounds 4a−m and 5a−m;
full bond lengths and angles table and CIF file for compound
4b, ORTEP and full refinement data of 4b. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: margherita.barbero@unito.it. Fax: +39-011-6707642.
Tel: +39-011-6707645.
■
(21) Barbero, M.; Crisma, M.; Degani, I.; Fochi, R.; Perracino, P.
Synthesis 1998, 1171.
(22) (a) Smith, G. F. Adv. Heterocycl. Chem. 1963, 2, 287. (b) Jones,
R. A. Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C.
W., Eds.; Pergamon Press: Oxford, 1984; Vol. 4, pp 201−312.
(23) Patil, V. D.; Dere, G. B.; Rege, P. A.; Patil, J. J. Synth. Commun.
2011, 41, 736.
Notes
The authors declare no competing financial interest.
(24) Zerbe, E.-M.; Wolper, C.; Roca Pinol, S.; Jones, P. G.;
̈
̃
ACKNOWLEDGMENTS
This work was supported by Italian MIUR and by Universita
degli Studi di Torino.
■
Blaschette, A. Z. Anorg. Allg. Chem. 2007, 633, 593.
(25) Moers, O.; Friedrichs, S.; Blaschette, A.; Jones, P. G. Z. Anorg.
Allg. Chem. 2001, 627, 2528.
̀
We thank Dr. Roberto Buscaino for mass spectrometric
assistance (exact ESI full mass).
(26) Desiraju, G. R.; Steiner, T. The Weak Hydrogen Bond; IUCr,
OxUniversity Press: Oxford, 1998.
(27) Agilent Technologies Ltd. UK, X-ray Diffraction Systems:
Oxford, U.K.
(28) Agilent Technologies. CrysAlisPro Software system, version
1.171.35.11, Agilent Technologies UK Ltd: Oxford, U.K., 2012.
(29) Sheldrick, G. M. SHELXTL, Version 5.1; Bruker AXS Inc.:
Madison, WI, 1997.
(30) Zeng, X.-F.; Ji, S.-J.; Wang, S.-Y. Tetrahedron 2005, 61, 10235.
(31) Cao, L.-L.; Wang, D.-S.; Jianga, G.-F.; Zhoub, Y.-G. Tetrahedron
Lett. 2011, 52, 2837.
(32) Huffman, R. W.; Bruice, T. C. J. Am. Chem. Soc. 1967, 89, 6243.
(33) Appleton, J. E.; Dack, K. N.; Green, A. D.; Steele, J. Tetrahedron
Lett. 1993, 34, 11529.
REFERENCES
(1) Olah, G. A. J. Org. Chem. 2001, 66, 5943.
(2) (a) Stadler, D.; Goepprt, A.; Rasul, G.; Olah, G. A.; Prakash, G. K.
S.; Bach, T. J. Org. Chem. 2009, 74, 312. (b) Kelly, D. P.; Jenkins, M. J.
J. Org. Chem. 1984, 49, 409. (c) Arnett, E. M.; Hofelich, T. C. J. Am.
Chem. Soc. 1983, 105, 2889.
■
(3) Schade, C.; Mayr, H.; Arnett, E. M. J. Am. Chem. Soc. 1988, 110,
567.
(4) McClelland, R. A.; Kanagasabapathy, V. M.; Banait, N. S.;
Steenken, S. J. Am. Chem. Soc. 1989, 111, 3966.
́
(5) (a) Denegri, B.; Matic, M.; Kronja, O. Eur. J. Org. Chem. 2010,
1440. (b) Nolte, C.; Mayr, H. Eur. J. Org. Chem. 2010, 1435.
(6) Benfatti, F.; Capdevila, M. G.; Zoli, L.; Benedetto, E.; Cozzi, P. G.
Chem. Commun. 2009, 5919 and references therein.
(7) (a) Okajima, M.; Soga, K.; Nokami, T.; Suga, S.; Yoshida, J. Org.
Lett. 2006, 8, 5005. (b) Nokami, T.; Watanabe, T.; Musya, N.;
Suehiro, T.; Morofuji, T.; Yoshida, J. Tetrahedron 2011, 67, 4664 and
references therein.
(8) Maji, B.; Joannesse, C.; Nigst, T. A.; Smith, A. D.; Mayr, H. J. Org.
Chem. 2011, 76, 5104.
(9) (a) Mayr, H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.;
Janker, B.; Kempf, B.; Loos, R.; Ofial, A. R.; Remennikov, G.;
Schimmel, H. J. Am. Chem. Soc. 2001, 123, 9500. (b) Minegishi, S.;
Kobayashi, S.; Mayr, H. J. Am. Chem. Soc. 2004, 126, 5174. (c) Kempf,
B. Ph. D. Dissertation, Ludwig-Maximilians-Universitat Munchen,
̈
̈
2003; Chem. Abs. 143, 305735.
(10) (a) Mayr, H.; Schneider, R.; Schade, C.; Bartl, J.; Bederke, R. J.
Am. Chem. Soc. 1990, 112, 4446. (b) Mayr, H.; Schneider, R.; Irrgang,
B.; Schade, C. J. Am. Chem. Soc. 1990, 112, 4454.
(11) Dilman, A. D.; Ioffe, S. L.; Mayr, H. J. Org. Chem. 2001, 66,
3196.
(12) Takekuma, S.; Tamura, M.; Minematsu, T.; Takekuma, H.
Tetrahedron 2007, 63, 12058 and references therein.
4287
dx.doi.org/10.1021/jo300099y | J. Org. Chem. 2012, 77, 4278−4287