Mechanistic insight into the formation of tetraarylazadipyrromethenes

Article abstract of DOI:10.1021/jo301972w

The tetraarylazadipyrromethene chromophore class has gained increasing attention in the past decade for a diverse set of scientific interests and applications. The most direct synthetic route available for their generation is heating of 4-nitro-1,3-diaryl

Full text of DOI:10.1021/jo301972w

Article
pubs.acs.org/joc
Mechanistic Insight into the Formation of
Tetraarylazadipyrromethenes
Marco Grossi, Aniello Palma, Shane O. McDonnell, Michael J. Hall, Dilip K. Rai, Jimmy Muldoon,
and Donal F. O’Shea*
Centre for Synthesis and Chemical Biology, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin
4, Ireland
S
* Supporting Information
ABSTRACT: The tetraarylazadipyrromethene chromophore class has gained
increasing attention in the past decade for a diverse set of scientific interests and
applications. The most direct synthetic route available for their generation is heating of
4-nitro-1,3-diarylbutan-1-ones with an ammonium source in an alcohol solvent. Despite
the practical simplicity, the reaction pathway(s) for these conversions are lengthy and
unclear. To gain insight into the steps involved, 15N labeling experiments with MS and
NMR analysis were utilized for conversion of 4-nitro-1,3-diphenylbutan-1-one 1 into
tetraphenylazadipyrromethene 2 with 15NH4OAc. To permit examination of later
stages of the reaction sequence to 2, the 15N-labeled potential intermediate 3,5-
diphenyl-1H-pyrrol-2-amine 10 was synthesized. A study of the dimerization pathway
utilizing 15N-labeled 10 revealed an unprecedented nitrogen rearrangement in the final
stages of the pathway involving a ring-opening/closing of a pyrrole ring. Utilizing 15N
labeling experiments we have shown that 2,4-diphenylpyrrole 8 can also react under the
reaction conditions with 3,5-diphenyl-2H-pyrrol-2-imine 7 (from oxidation of 10) to
produce 2. Overall in the conversion of 1 into 2, two related pathways are ongoing concurrently; the first involves a dimerization
of 3,5-diphenyl-2H-pyrrol-2-imine 7, and the other a reaction of 7 with 2,4-diphenylpyrrole 8.
INTRODUCTION
■
Use of isotope-labeled compounds in conjunction with mass
spectrometry and NMR is a powerful tool for studying reaction
pathways as well as metabolic patterns.1 In this report, the
stable isotope 15N labeling was combined with tandem mass
spectrometry (MS/MS) experiments and NMR data to gain
insight into the formation of N-(3,5-diaryl-2H-pyrrol-2-
ylidene)-3,5-diphenyl-1H-pyrrol-2-amines (tetraarylazadipyrro-
methenes) 2 (Scheme 1). Tetraarylazadipyrromethenes 2 were
Figure 1. Chelated tetraarylazadipyrromethenes 3.
high fluorescence quantum yields in the near-infrared spectral
region and have been adapted toward applications as
fluorochromes,4 sensors/energy transfer cassettes,5 nanoparticle
conjugates for real-time fluorescence imaging,6 and donor/
acceptor conjugates for solar cell applications.7 Additionally,
they have been further modified to act as highly effective light-
activated therapeutics,8 and the d-block metal chelates have
been proposed as supramolecular architecture building blocks
as well as medical chemical agents (Figure 1).9
Scheme 1. Synthesis of Tetraarylazadipyrromethenes 2
first reported by M. Rogers in the early 1940s as unexpected
deep blue colored products obtained from the treatment of
diaryl-γ-nitro ketones 1 with various ammonia sources.2 Using
the limited analytical techniques available at the time, it was
proven that the blue chromophore obtained from the reaction
of 2 equiv of the relatively simple substrate 1 was the nitrogen-
bridged dipyrrole structure 2.
RESULTS AND DISCUSSION
■
Despite their growing importance, a mechanism of formation of
2 starting from diaryl-γ-nitro ketones remains elusive. In
Roger’s original paper, 1 (Ar, Ar1 = Ph) was heated neat (no
solvent) with an excess of ammonium formate at 180 °C for 15
A renewed interest in this compound class has rapidly grown
in recent years following our reports on their BF2 and B(OR)2
chelates 3 (Figure 1).3 These boron-chelated derivatives have
Received: September 13, 2012
© XXXX American Chemical Society
A
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min and then at 190 °C for a further 15 min. After cooling, the
product 2 was isolated by trituration with methanol in a 33%
yield (Scheme 2).2a Work from our own laboratory has shown
and subsequent condensation with nonconverted 8 to generate
2 (Scheme 3, pathway ii).12 The means by which 8 is partially
converted into 9 is not discussed. While we anticipated that
pathway i would be plausible, a further alternative pathway iii
could also be considered in which 2,4-diphenylpyrrole 8 is
produced within the reaction mixture but reacts with 7 to
generate 2 (Scheme 3). In this report we describe our efforts to
gain insight into potential routes i and iii with a focus on 3,5-
diphenyl-2H-pyrrol-2-imine intermediate 7 and the pathways
by which it can produce 2.
Scheme 2. Reaction Conditions for the Synthesis of 2
At the outset, a series of 15N labeling studies were carried out
in an effort to shed some light on the overall pathway. The use
of this isotope allowed the employment of mass spectrometry
and 15N NMR techniques to characterize the labeled products.
On the basis of the outline of pathway i, it would be a plausible
expectation that by utilizing a 15N-labeled source of ammonia,
the label would be incorporated into the two pyrrole nitrogen
positions leaving the bridging nitrogen unlabeled. With this
goal in mind, 4-nitro-1,3-diphenylbutan-1-one 1 was heated
with 15NH4OAc (35 equiv) in ethanol under reflux for 24 h,
and the product, which precipitated from the reaction, was
analyzed by 15N NMR and electrospray ionization mass
spectrometry (ESI-MS) in the positive ion mode. The 15N
NMR results were initially inconclusive (vide infra), as three
signals were observed with chemical shifts of −86.2, −175.7,
and −176.2 ppm (Figure 5, spectrum A). The positive mode
ESI-MS of 2 from the 14N ammonium acetate gave the
expected [M + H]+ ion peak of m/ z 450 and peaks of lesser
abundant ions at m/z 451 and m/z 452 arising from the natural
abundance of 13C (Figure 2A). In contrast, the ESI-MS data of
2 generated using 15NH4OAc had an obvious absence of a peak
at 450 m/z with a distribution of peaks from 451 to 455 m/z
(Figure 2B). The most abundant was that of the trilabeled
species (peak 453 m/z) followed by dilabeled species (peak 452
m/z) and monolabeled (peak 451 m/ z). The composition of
that a comparable 35% yield can be obtained under the milder
conditions of reflux in ethanol for 24 h in the presence of 35
equiv of ammonium acetate.3b
Insight into the route(s) by which 2 is formed is clearly of
interest, but the overall reaction sequence or sequences contain
numerous intermediates along the pathway. Despite this, 2
equiv of 1 are clearly incorporated into the final product 2 and
while the origin of the carbon skeleton in 2 is evident, the same
cannot be stated for the nitrogens.
A plausible start of the reaction pathway(s) to 2 could
involve generation of enamine intermediate 4 from 1 and
ammonia followed by nucleophilic addition to the aci-nitro
tautomer to generate 5 from which several potential pathways
may be considered (Scheme 3). Route i evokes an elimination
Scheme 3. Alternative Route Outlines to 2
of water and tautomerization to N-(3,5-diphenyl-1H-pyrrol-2-
yl)hydroxylamine 6 and subsequent further dehydration to
generate 3,5-diphenyl-2H-pyrrol-2-imine 7 (Scheme 3, pathway
i).10 From 7, a formal dismutation, dimerization, and loss of
ammonia could provide 2 (Scheme 3).11 Alternatively, route ii
has been postulated by others, in which an elimination of water
and HNO could generate 2,4-diphenylpyrrole 8 followed by a
partial in situ conversion to 2-nitroso-3,5-diphenyl pyrrole 9
Figure 2. A: Positive mode ESI-MS of 2 generated with NH4OAc. B:
ESI-MS of 2 generated with 15NH4OAc.
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the isotopologue mixture from the mass spectrum as shown in
Figure 2B was calculated by relative peak height to give a ratio
of 9:6:1 of the tri:di:mono labeled species, respectively (Figure
3).
and NaNO2, respectively.13 The systematic condensation of
unlabeled and labeled 2,4-diphenylpyrroles 8 and 8-{1-15N1}
with 2-nitroso-3,5-diphenylpyrroles 9, 9-{1-15N1} and 9-
{2-15N1} was performed in ethanol/acetic acid generating the
four derivatives 2-{1-15N1}, 2-{6-15N1}, 2-{1,6-15N2}, and 2-
{1,11-15N2} (Figure 4).
15N NMR for 2-{1-15N1}, 2-{6-15N1}, 2-{1,6-15N2}, and 2-
{1,11-15N2} were recorded in CDCl3 using nitromethane as
reference (Figure 5, spectra B−E, respectively). Monolabeled 2-
Figure 3. All possible 15N (red color) isotopologues and isotopomers
of 2 with calculated positive mode m/z values.
This result shows that for the most abundant trilabeled
isotopologue 2-{1,6,11-15N3}, the nitrogen from the nitro
group of 1 is not incorporated into the final product. To assign
the labeled nitrogen position(s) in the di- and monolabeled
species, two different isotopomers 2-{1,6-15N2}, 2-{1,11-15N2}
and 2-{1-15N1}, 2-{6-15N1} must be considered for each case
(Figure 3). To achieve this, we turned to ESI-MS/MS
experiments with examination of the fragmentation patterns
of the m/z 452 and 451 peaks. To be confident in the
interpretation of MS/MS fragmentation results from the
isotope mixture and to assign 15N NMR resonances, authentic
samples of the four differently labeled derivatives were first
individually synthesized following our previously reported
multistep route utilizing a pyrrole/nitrosopyrrole condensa-
tion.13
Figure 5. 15N NMR spectra of A: product 2 generated with
15NH4OAc. B−E: rationally synthesized isotopologues and iso-
topomers of 2.
{1-15N1} and 2-{6-15N1} gave single peaks with chemical shifts
of −176.2 and −86.2 ppm which could be assigned to the
pyrrole and bridging exocyclic nitrogens, respectively.14
Dilabeled compound 2-{1,6-15N2} which contains one pyrrole
15N label and one exocyclic 15N label recorded both chemical
shifts of −176.2 and −86.2 ppm, respectively. Structurally
revealing its dilabeled isotopomer 2-{1,11-15N2} gave the
expected one 15N pyrrole signal but with a chemical shift of
−175.7 ppm which is marginally different from that of either 2-
{1,6-15N2} or 2-{1-15N1}. As 2 is a quasiaromatic system with
N−H tautomerization making both pyrrole nitrogens equiv-
alent, the different 15N pyrrole chemical shifts can be attributed
to a heavy atom equilibrium isotope effect on the averaged
chemical shift resonances of 2-{1,6-15N2} and 2-{1,11-15N2}.15
This subtle yet important difference allows the NMR
differentiation of 2-{1-15N1}, 2-{1,11-15N2}, and 2-
{1,6,11-15N3} by 15NMR even as label mixtures (Figure 5,
spectra A, B, E).
The 15N-labeled pyrrole 8-{1-15N1} was generated by a Nef
reaction on 1 to yield the corresponding keto-aldehyde (4-oxo-
2,4-diphenylbutanal) followed by condensation with
15NH4OAc (Figure 4). Synthesis of the 15N-labeled nitroso
pyrroles 9-{2-15N1} and 9-{1-15N1} was achieved by reaction of
the corresponding pyrroles 8 and 8-{1-15N1} with Na15NO2
The ESI-MS of the dilabeled isotopomers 2-{1,6-15N2} and
2-{1,11-15N2} gave the expected molecular ion peaks at 452 m/
z. Encouragingly, ESI-MS/MS of the two isotopic isomers
showed differing fragmentation patterns such that 2-{1,6-15N2}
gave 218/219 m/z and 232/233 m/z fragments, whereas 2-
{1,11-15N2} fragmented to 219 m/z and 232 m/z (Figure 6,
Figure 4. Rational syntheses of 15N (red color) isotopologues and
isotopomers of 2.
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to air oxidation (Scheme 4).2a,16 As a formal oxidation of
amino-pyrrole 10 equates to 7, a potential advanced
Scheme 4. Synthetic Route to 2 via 3,5-Diphenyl-1H-pyrrol-
2-amine 10
intermediate of the reaction sequence as shown in Scheme 2,
an examination of its conversion into 2 offered an opportunity
to probe potential final stages of the reaction sequence.
Synthetic access to 10 could be achieved by reduction of the
available 2-nitroso-3,5-diphenylpyrrole 9 (Scheme 4). This
route was previously shown to be viable by reduction of 9 with
Adam’s catalyst producing a solution of 10 which, without
isolation, underwent air oxidation leading to dimerization with
loss of ammonia to give 2.2a
For our investigation of this pathway, alternative reducing
conditions of catalytic Pd/C and H2 (1 atm) in MeOH for 2 h
at rt proved optimal (Scheme 5). In general, the isolation of
Scheme 5. Route to 2 via Dimerization of 10
Figure 6. A: Positive mode ESI-MS/MS for 2-{1,6-15N2}. B: ESI-MS/
MS for 2-{1,11-15N2}. C: ESI-MS/MS for the 452 m/z peak of labeled
products obtained from reaction of 1 with 15NH4OAc.
spectra A and B). This is consistent with the unsymmetrical
labeling pattern of 2-{1,6-15N2} (one pyrrole 15N and one
bridging 15N) and the symmetrical labeling (both pyrrole 15N)
of 2-{1,11-15N2}. Investigation of the MS/MS fragmentation
pattern for the m/z 452 peak for the product from the reaction
of labeled ammonium acetate and 1 showed it to be a mixture
of both isotopomers 2-{1,6-15N2} and 2-{1,11-15N2} (Figure
6C). Taken with the 15N NMR data, these results illustrated
that scrambling of nitrogen positions occurred during the
reaction sequence for the formation of the dilabeled species.
In a similar fashion, monolabeled 2-{1-15N1} and 2-{6-15N1}
could be distinguished by their fragmentation peaks at 218/219,
231/232, and 218/232 m/z, respectively (Figure S1, Support-
ing Information). The main findings from these initial 15N
labeling experiments were that the nitro group of the starting
material in 1 was not found in over 50% of the isolated product,
and exchanging of the nitrogen positions could be observed in
the dilabeled product, as both isotopomers could be detected.
To probe the later stages of the formation of 2, the reactivity
of 3,5-diphenyl-1H-pyrrol-2-amine 10 was selected for further
investigation. In addition to the synthetic approaches to 2
outlined above, 10 is also known to generate 2 when exposed
amino-pyrroles is often problematic due to their air
sensitivity.17 As such, following reduction of 9, the solution
of 10 was rapidly filtered to remove the Pd and directly treated
with acetic anhydride, and the product isolated following silica
gel chromatography. Analysis of the product was consistent
with the expected C-2 amido-substituted pyrrole structure 11
(Scheme 5). In subsequent attempts it was found that with
careful exclusion of air during workup, the C-2 amino-pyrrole
10 could be isolated and characterized with HRMS and NMR.
In addition, following reduction of isotopomers 9-{1-15N1} and
9-{2-15N1}, the 15NMR analysis of 10-{1-15N1} and 10-{2-15N1}
showed single signals at −240.0 and −337.1 ppm, respectively,
which are consistent with 15N-labeled pyrrole and amino
nitrogens.17b,18
Heating an air-exposed ethanolic solution of 10 and
NH4OAc under reflux for 18 h provided the azadipyrromethene
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Scheme 7. 15N Rearrangement upon Oxidative Dimerization
of 10-{1-15N1} and 10-{2-15N1}
2 in a 56% yield. In the absence of NH4OAc, 2 was also formed
but in a lower 8% yield. These conversions would be consistent
with an oxidation of 10 to 7, subsequent in situ condensation
with a second equivalent of 10, and loss of ammonia via an
intermediate 12 yielding 2 (Scheme 5).19 A similar mechanism
with structurally related intermediates has also been evoked in
the formation of phthalocyanines starting from phthalonitriles
and of methylene blue.20
To investigate the possibility of nitrogen interchange during
the conversion of 10 into 2, the oxidative/dimerization of 15N-
labeled amino-pyrroles 10-{1-15N1} and 10-{2-15N1} were
studied (Scheme 6). Remarkably, following heating of 10-
Scheme 6. 15N Rearrangement upon Oxidative Dimerization
of 10
{1-15N1} (pyrrole nitrogen labeled) under reflux in EtOH
(without NH4OAc), the ESI-MS and 15N NMR analysis
revealed that only a mono-15N-labeled product was obtained.
This indicated that a pyrrole-labeled nitrogen had been
exchanged, and comparison of the 15N NMR chemical shift
(−176.2 ppm) proved that the isotopomer formed was 2-
{1-15N1}. This rearrangement was confirmed by repeating the
same reaction conditions with 10-{2-15N1} (amino nitrogen
labeled) which gave a dilabeled product by MS and two 15N
signals in the NMR spectrum (−86.2 and −176.2 ppm)
corresponding to the isotopomer 2-{1,6-15N2) containing one
label in a pyrrole ring and a labeled bridging nitrogen (Scheme
6).
These results show that a rearrangement has taken place that
exchanged one pyrrole nitrogen for the exocyclic bridging
nitrogen. While the exact sequence by which this occurs
remains as yet uncertain, this would require a pyrrole opening
and reclosing to take place during the final stages of the
reaction pathway (Scheme 7). A plausible pyrrole ring-opened
intermediate 13 is akin to the intermediate generated in the
pyrrole synthesis from the reductive ring contraction of 1,2-
pyridazines.21 Reclosing to a five-membered ring would give 14,
which upon elimination of ammonia would generate products
2-{1-15N1} or 2-{1,6-15N2} depending upon the position of the
15N label in the starting material (Scheme 7).22 This
unprecedented rearrangement can account for the formation
of both dilabeled isotopomers 2-{1,6-15N2} and 2-{1,11-15N2}
in the reaction of 1 with 15NH4OAc as described in Scheme 3
but does not necessarily explain the fact that trilabeled 2-
{1,6,11-15N3} is the major isotopologue obtained.
imately 40:60 ratio (15N NMR analysis showed a scrambling of
label positions) in contrast to the dilabeled 2-{1,6-15N2} alone
being obtained in the absence of an external 14N source. This
shows that even at the later stages of the reaction sequence,
intermolecular nitrogen exchange can occur, with intermediate
7 being the most likely candidate for exchange.23 This exchange
could account for trinitrogen-labeled 2 being the predominant
labeled species obtained from the reaction of 1 with
15NH4OAc.24
Attempts to directly detect formation of pyrrole intermedi-
ates in the conversion of 1 into 2 by TLC were unsuccessful
presumably because of their low concentration. More sensitive
MS and HPLC techniques revealed the presence of
diphenylpyrrole 8 in the reacting mixture after 1 h (Scheme
8). In situ MS observation of other pyrrole intermediates was
not achieved, but this could be attributed to their lower stability
preventing direct observation. The observation of 8 in the
reaction mixture, though it is not obtained in any significant
quantities at the end of the reaction, pointed toward the
existence of an additional pathway, which could proceed
concurrently with pathway i (Scheme 3). For this to be the
To explore the potential for intermolecular nitrogen
exchange during the conversion of 10 into 2, the oxidative
dimerization of 10-{2-15N1} in EtOH/14NH4OAc was carried
out. Revealingly, the MS product analysis showed a mixture of
mono- and dilabeled isotopologues obtained in an approx-
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into the tetraphenylazadipyrromethene 2 have been inves-
tigated using 15N labeling methods. The mixture of mono-, di-,
and trilabeled species obtained from this reaction indicated a
more complicated process than might first be envisaged.
Further insight into the reaction pathways was obtained by
examination of the latter stages of the reaction sequence
starting from 15N-labeled 3,5-diphenyl-1H-pyrrol-2-amine 10.
This provided unique insight into its oxidative dimerization
process with an unexpected exchange of a pyrrole nitrogen with
an exocyclic nitrogen taking place in the final stages of the
reaction pathway. To the best of our knowledge, this is the first
illustration of this nitrogen positional rearrangement and may
not be confined to this example alone.27 This rearrangement
provides an understanding of the original distribution of 15N
labels observed from the conversion of 1 into 2 using a 15N
ammonia source. A second concurrent pathway was also
revealed by our study in which 2,4-diphenylpyrrole 8, which
can be detected in the reaction mixture, can react with the same
intermediate 7. While it is not unusual to observe different
pathways in a multicondensation style heterocyclic synthesis in
which the undesired pathway produces an impurity, in this case
an atypical situation arises in which the divergent pathway
produces a potential impurity 8 which does not accumulate but
rebounds back into a complementary product reaction pathway
as it is intercepted by 7.
Scheme 8. Direct Evidence for the Formation of 8 from 1
case, two possibilities must exist for the intermediate 5 in which
it can either advance to 7 or to the diphenylpyrrole 8. As shown
above, 7 can dimerize to form the product 2 (route i), but two
possibilities could be envisaged for the conversion of 8 into 2
(Scheme 3, routes ii or iii). We considered route ii which
requires in situ conversion of 8 into 9 less likely, with reaction
of 8 and 7 (route iii) more probable.
To investigate the reaction pathway in which 7 and 8
combine to produce 2, two experiments were carried out using
15N-labeled diphenylpyrrole 8-{1-15N1}. Reaction of equal
molar equivalents of 8-{1-15N1} and amino-pyrrole 10 in
EtOH/NH4OAc provided the monolabeled isotopomer 2-
{1-15N1} and unlabeled 2 in a 1:1 ratio, illustrating that the two
pathways i and iii are operating concurrently (Scheme 9). One
Scheme 9. Trapping of in Situ-Generated 7 from 1 or 10
In conclusion, the use of 15N labeling has shed light on the
complex pathways that lead to tetraarylazadipyrromethenes
from 4-nitro-1,3-diarylbutan-1-ones precursors. Evidence has
been provided to support the presence of a key intermediate 7
which can dimerize with loss of ammonia to form 2 or react
with 2,4-diphenylpyrrole 8. Both pathways operate concur-
rently under the reaction conditions that convert 1 into 2.
EXPERIMENTAL DETAILS
■
Proton-decoupled 15N NMR spectra were recorded directly at 60.79
MHz using a 45° pulse width of 12.5 μs, a relaxation delay of 1 s, and
acquisition time of 1.23 s with a spectral window of 26595.7 Hz (31.7
ppm to −405.7 ppm). Spectra were recorded at rt using nitromethane
as internal standard. The ESI-MS and ESI-MS/MS were performed on
a Quattro microtandem quadrupole instrument. The HRMS data were
recorded on an LC-time of flight mass spectrometer.
pathway in which 10 is in situ oxidized to 7 and trapped by 8-
{1-15N1} generating 2-{1-15N1}, and the other in which 10
reacts with 7 to produce unlabeled 2.25 This result indicated
that it may be possible to intercept the intermediate 7 as it is
being produced from the diphenylnitroketone 1. When 8-
{1-15N1} was included as a reagent in the typical reaction
conditions of 1/NH4OAc/EtOH, the result was most revealing
(Scheme 9). Following reflux in NH4OAc/EtOH, the two
substrates provided 2-{1-15N1} as the only isotopologue
showing that 8-{1-15N1} could efficiently react with 7 as it
was generated from 1. In contrast to the result described above,
predominantly 2-{1-15N1} was formed with very little unlabeled
2 observed. This can be explained by the fact that at any one
time only a low concentration of 7 is being generated in the
presence of a larger excess of pyrrole 8-{1-15N1}, thereby
biasing toward pathway iii and away from the dimerization of 7
via pathway i. This result has added importance, as it offers a
new synthetic approach to tetraarylazadipyrromethenes con-
taining differing aryl substituents on each pyrrole ring (without
the need to synthesize nitroso-pyrroles as shown in Figure 4)
by the reaction of a diarylnitroketone with a diarylpyrrole
containing different aryl groups.26
N-(3,5-Diphenyl-2H-pyrrol-2-ylidene)-3,5-diphenyl-1H-pyr-
rol-2-amine 2 Using 14NH4OAc.3a In a round-bottom flask, 1 (0.1 g,
0.37 mmol) and 14NH4OAc (1 g, 13 mmol) were dissolved in ethanol
(5 mL) and heated under reflux for 24 h. During the course of the
reaction, the product precipitated from the reaction mixture. The
reaction was cooled to rt and filtered, and the solid was washed with
cold ethanol (2 × 2 mL) to yield product 2 as a blue-black solid (29
mg, 35%): mp 288−290 °C. 1H NMR (400 MHz, CDCl3) δ: 8.06 (d, J
= 7.4 Hz, 4H), 7.96 (d, J = 7.5 Hz, 4H), 7.57−7.51 (m, 4H), 7.50−
7.41 (m, 6H), 7.39−7.34 (m, 2H), 7.21 (s, 2H) ppm. 13C NMR (100
MHz, CDCl3) δ: 155.3, 149.8, 142.8, 133.9, 132.3, 130.2, 129.3, 129.2,
128.4, 128.2, 126.7, 115.1 ppm. ESI-MS: m/z [M + H]+ 450.2 (100%);
451.2 (37%); 452.2 (8%).
Synthesis of N-(3,5-Diphenyl-2H-pyrrol-2-ylidene)-3,5-di-
phenyl-1H-pyrrol-2-amine 2 Using 15NH4OAc. In a round-bottom
flask, 1 (0.1 g, 0.37 mmol) and 15NH4OAc (1 g, 13 mmol) were
dissolved in ethanol (5 mL) and heated under reflux for 24 h. During
the course of the reaction, the product precipitated from the reaction
mixture. The reaction was cooled to rt, filtered and the solid was
washed with cold ethanol (2 × 2 mL) to yield the 15N-labeled product
1
2 (32 mg, 38%) as a mixture of 15N-labeled isomers. H NMR (600
MHz, CDCl3) δ: 8.08−8.05 (m, 4H), 7.98−7.95 (m, 4H), 7.56−7.52
(m, 4H), 7.49−7.49 (m, 2H), 7.45−7.41 (m, 4H), 7.38−7.34 (m, 2H),
7.21 (s, 2H) ppm. 15N NMR (60.8 MHz, CDCl3) δ: −86.2, −175.7,
−176.2 ppm, 2-{115N1} (−176.2 ppm); 2-{6-15N1} (−86.2 ppm); 2-
In summary, the reaction pathways involved in the
conversion of diphenylnitroketone 1 and ammonium acetate
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{1,6-15N2} (−176.2, −86.2 ppm); 2-{1,11- 15N2} (−175.7 ppm), 2-
{1,6,11- 15N3} (−175.7, −86.2 ppm). ESI-MS: m/z [M + H]+ 451.2
(10%); 452.2 (57%); 453.2 (100%); 454.2 (32%); 455.2 (7%).
2,4-Diphenyl-1H-pyrrole, 8-{1-15N1}. A stirred suspension of 1
(0.5 g, 1.8 mmol) in MeOH (5 mL) was treated at rt with a solution of
KOH (0.52 g, 9.3 mmol) in MeOH (20 mL). After 1 h, the clear
solution was added dropwise to a solution of concentrated H2SO4 (3.8
mL) in MeOH (20 mL) at 0 °C, following which the solution was
allowed to warm to rt and stirred for a further 1 h. Water (45 mL) and
ice (45 g) were added, and the mixture was neutralized to pH 7 with
aqueous 4 M NaOH. The stirred mixture produced a white solid
which was filtered, washed with water, dried, and used for the
following step without further purification. The solid was dissolved in
acetic acid (9 mL), and 15NH4OAc (0.35 g, 4.5 mmol) was added. The
mixture was heated at 100 °C for 1 h, cooled to rt, poured in ice (100
g), and neutralized to pH 7 with 4 M NaOH. The precipitate was
filtered, washed with water, and dried. The solid was triturated with
Et2O to yield 8-{1-15N1} as a light pink solid (0.22 g, 56%): mp 173−
175 °C. 1H NMR (500 MHz, DMSO-d6) δ: 11.42 (d, J = 95.7 Hz, 1H,
15NH coupling), 7.68 (d, J = 7.6 Hz, 2H), 7.61 (d, J = 7.5 Hz, 2H),
7.40−7.35 (m, 2H), 7.35−7.29 (m, 3H), 7.18 (t, J = 7.3 Hz, 1H), 7.12
(t, J = 7.3 Hz, 1H), 6.95 (bs, 1H) ppm. 13C NMR (125 MHz, DMSO-
d6) δ: 135.7 (d, J = 1.7 Hz), 132.6 (d, J = 2.2 Hz), 132.2 (d, J = 13.4
Hz), 128.6, 128.5, 125.6, 125.0, 124.7 (d, J = 3.5 Hz), 124.4, 123.4,
116.5 (d, J = 13.5 Hz), 103.2 (d, J = 4.0 Hz) ppm. 15N NMR (60.8
MHz, DMSO-d6) δ: −227.3 ppm. HRMS (EI) calcd for C16H1315N
[M]+ 220.1018, found 220.1010.
NMR (500 MHz, CDCl3) δ: 8.08−8.05 (m, 4H), 7.98−7.94 (m, 4H),
7.57−7.52 (m, 4H), 7.50−7.41 (m, 6H), 7.39−7.34 (m, 2H), 7.22−
7.20 (m, 2H) ppm. 15N NMR (60.8 MHz, CDCl3) δ: −176.2 ppm.
HRMS (ES) calcd for C32H2414N215N [M + H]+ 451.1941, found
451.1955.
N-(3,5-Diphenyl-2H-pyrrol-2-ylidene)-3,5-diphenyl-1H-pyr-
rol-2-amine, 2-{6-15N1}. Compound 8 (5.0 mg, 0.0228 mmol) and 9-
{2-15N1} (5.7 mg, 0.0228 mmol) were dissolved in a mixture AcOH
(0.1 mL) and EtOH (0.6 mL), and the solution was heated under
reflux for 24 h. The solution was cooled to rt, and the precipitate was
collected by filtration, washed with cold EtOH, and dried. The product
was obtained as a dark blue solid (4.6 mg, 45%): mp 290−291 °C. 1H
NMR (500 MHz, CDCl3) δ: 8.09−8.05 (m, 4H), 7.98−7.95 (m, 4H),
7.57−7.52 (m, 4H), 7.50−7.41 (m, 6H), 7.39−7.34 (m, 2H), 7.21
(s,2H) ppm. 15N NMR (60.8 MHz, CDCl3) δ: −86.2 ppm. HRMS
(ES) calcd for C32H2414N215N [M + H]+ 451.1941, found 451.1924.
N-(3,5-Diphenyl-2H-pyrrol-2-ylidene)-3,5-diphenyl-1H-pyr-
rol-2-amine, 2-{1,6-15N2}. Compound 8-{1-15N1} (5.0 mg, 0.0227
mmol) and 9-{2-15N1} (5.6 mg, 0.0227 mmol) were dissolved in a
mixture of AcOH (0.1 mL) and EtOH (0.6 mL), and the solution was
heated under reflux for 24 h. The solution was cooled to rt, and the
precipitate was collected by filtration, washed with cold EtOH, and
dried. The product was obtained as a dark blue solid (7.1 mg, 69%):
mp 290−291 °C. 1H NMR (600 MHz, CDCl3) δ: 8.08−8.05 (m, 4H),
7.98−7.94 (m, 4H), 7.56−7.52 (m, 4H), 7.50−7.45 (m, 2H), 7.45−
7.41 (m, 4H), 7.38−7.34 (m, 2H), 7.22−7.20 (m, 2H) ppm. 15N
NMR (60.8 MHz, CDCl3) δ: −86.2, −176.2 ppm. 15N NMR (60.8
MHz, CDCl3) δ: −86.2, −176.2 ppm. HRMS (ES) calcd for
C32H2414N15N2 [M + H]+ 452.1911, found 452.1917.
N-(3,5-Diphenyl-2H-pyrrol-2-ylidene)-3,5-diphenyl-1H-pyr-
rol-2-amine, 2-{1,11-15N2}. Compound 8-{1-15N1} (5 0 mg, 0.0227
mmol) and 9-{1-15N1} (5.6 mg, 0.0227 mmol) were dissolved in a
mixture AcOH (0.1 mL) and EtOH (0.6 mL), and the solution was
heated under reflux for 24 h. The solution was cooled to rt, and the
precipitate was collected by filtration, washed with cold EtOH, and
dried. The product was obtained as a dark blue solid (5.3 mg, 52%):
mp 287−288 °C. 1H NMR (600 MHz, CDCl3) δ: 8.08−8.05 (m, 4H),
7.98−7.95 (m, 4H), 7.56−7.53 (m, 4H), 7.49−7.49 (m, 2H), 7.45−
7.41 (m, 4H), 7.38−7.35 (m, 2H), 7.21 (s, 2H) ppm. 15N NMR (60.8
MHz, CDCl3) δ: −175.7 ppm. HRMS (ES) calcd for C32H2414N15N2
[M + H]+ 452.1911, found 452.1906.
2-Nitroso-3,5-diphenyl-1H-pyrrole, 9-{1-15N1}. To a stirred
solution of 8-{1-15N1} (0.15 g, 0.68 mmol) in EtOH (7 mL) was
added concentrated HCl (0.13 mL), followed by a dropwise addition
of aqueous NaNO2 (54 mg, 0.78 mmol, in 1.3 mL of H2O). The
solution was stirred for 30 min and then cooled to 0 °C, and another
portion of concentrated HCl (0.67 mL) was added. The solution was
stirred for 1 h, and the resulting red solid was collected by filtration
and washed with Et2O. The solid was dissolved in minimal EtOH, an
excess of aqueous NaOAc and ice was added, and the solution was
stirred for 1 h. The resulting solid was collected by filtration, washed
with water, dried, and purified by chromatography on alumina
(EtOAc/cyclohexane). A green solid was obtained (0.11 g, 65%): mp
1
140−141 °C. H NMR (400 MHz, CDCl3) δ: 8.21−8.15 (m, 2H),
7.84−7.77 (m, 2H), 7.54−7.46 (m, 6H), 7.15 (d, J = 2.9 Hz, 1H) ppm.
13C NMR (125 MHz, CDCl3) δ: 163.1 (d, J = 11.6 Hz), 141.5, 132.0,
131.4, 129.8, 129.6, 129.5 (b), 129.0, 126.9 (b), 113.0 (b) ppm. 15N
NMR (60.8 MHz, DMSO-d6) δ: −248.8 ppm. HRMS (ES) calcd for
C16H1314N15NO [M + H]+ 250.0998, found 250.0997.
N-(3,5-Diphenyl-1H-pyrrol-2-yl)acetamide, 11. In a round-
bottom flask under inert atmosphere, compound 9 (0.15 g, 0.6 mmol)
and activated Zn powder (0.90 g, 1.2 mmol) were suspended in
ethanol 10% HOAc (20 mL). The reaction mixture was stirred for 2 h.
The resulting suspension was cannulated into acetic anhydride (30
mL), and the solution was stirred for 4 h at rt. The solution was slowly
poured into a saturated solution of NaHCO3 (100 mL) and extracted
with ethyl acetate (3 × 100 mL). The organic layers were washed with
water (2 × 100 mL) and brine (100 mL) and dried over sodium
sulfate. The crude material was purified by chromatography on silica
gel using DCM:cyclohexane 9:1, respectively, yielding the purified
2-Nitroso-3,5-diphenyl-1H-pyrrole, 9-{2-15N1}. To a stirred
solution of 8 (0.2 g, 0.91 mmol) in EtOH (9 mL) was added
concentrated HCl (0.18 mL), followed by a dropwise addition of
aqueous Na15NO2 (74 mg, 1.05 mmol, in 1.8 mL of H2O). The
solution was stirred for 30 min and then cooled to 0 °C, and another
portion of concentrated HCl (0.9 mL) was added. The solution was
stirred for 1 h, and the resulting red solid was collected by filtration
and washed with Et2O. The solid was dissolved in minimal EtOH, an
excess of aqueous NaOAc and ice was added, and the solution was
stirred for 1 h. The resulting solid was collected by filtration, washed
with water, dried, and purified by chromatography on alumina
(EtOAc/cyclohexane). A green solid was obtained (0.165 g, 73%): mp
1
product as a colorless solid. (0.110 g, 70%): mp: 168−169 °C; H
NMR (400 MHz, CDCl3) δ: 10.76 (bs, 1H), 7.77 (bs, 1H), 7.51−7.49
(d, J = 8.0 Hz, 2H), 7.46−7.34 (m, 6H), 7.29−7.26 (m, 1H), 7.20−
7.17 (t, J = 8.0 Hz, 1H), 6.53−6.52 (d, J = 4.0 Hz, 1H), 2.20 (s, 3H)
ppm. 13C NMR (125 MHz, CDCl3) δ 167.9, 135.0, 132.1, 129.7,
128.8, 127.3, 126.3, 126.1, 126.0, 125.9,123.3, 110.2, 104.2, 23.9 ppm.
IR (KBr disk) cm−1: 3242.73, 3046.03, 1650.31, 1614. ESI-MS: m/z
[M + H]+ = 277.1. HRMS Calcd for C18H17N2O [M + H]+ 277.1341,
found 277.1347.
1
140−141 °C. H NMR (400 MHz, CDCl3) δ: 8.21−8.16 (m, 2H),
7.82−7.78 (m, 2H), 7.54−7.47 (m, 6H), 7.15 (s 1H) ppm. 13C NMR
(125 MHz, CDCl3) δ: 163.0 (d, J = 7.5 Hz), 148.2 (b), 141.6, 132.0,
131.4, 129.8, 129.7, 129.6, 129.4, 129.0, 127.0, 113.0 (b) ppm. 15N
NMR (60.8 MHz, DMSO-d6) δ: −326.0 ppm. HRMS (ES) calcd for
C16H1314N15NO [M + H]+ 250.0998, found 250.0998.
3,5-Diphenyl-1H-pyrrol-2-amine, 10. Compound 9 (100 mg,
0.40 mmol) was dissolved in methanol (11 mL), and 10% Pd on
activated charcoal (21 mg, 0.02 mmol) was added. The suspension was
frozen using liquid nitrogen, and the apparatus was evacuated then
filled with H2 (1 atm). The mixture was allowed to reach rt and stirred
for 2 h. The suspension was filtered over a plug of Celite, and the filter
cake was washed with methanol, carefully avoiding air to enter in
contact with the mixture. The solvent was removed under vacuo
(below 25 °C), yielding a light blue powder (89 mg, 94%): mp 144−
N-(3,5-Diphenyl-2H-pyrrol-2-ylidene)-3,5-diphenyl-1H-pyr-
rol-2-amine, 2-{1-15N1}. Compound 8-{1-15N1} (5.0 mg, 0.227
mmol) and 9 (5.6 mg, 0.227 mmol) were dissolved in a mixture AcOH
(0.1 mL) and EtOH (0.6 mL), and the solution was heated under
reflux for 24 h. The solution was cooled to rt, and the precipitate was
collected by filtration, washed with cold EtOH, and dried. The product
was obtained as a dark blue solid (5.6 mg, 55%): mp 289−290 °C. 1H
G
dx.doi.org/10.1021/jo301972w | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1
145 °C (decomp). H NMR (500 MHz, DMSO-d6) δ: 10.44 (s, 1H,
Conversion of 10-{2-15N1} into 2-{1,6-15N2} in the Absence of
NH4OAc. A solution of 10-{2-15N1} (40 mg, 0.17 mmol) in EtOH
(4.3 mL) was heated under reflux for 18 h. The precipitate that was
formed during the reaction was collected by filtration, washed with
cold EtOH, and dried. Compound 2-{1,6-15N2} (2.0 mg, 5%) was
NH), 7.50−7.44 (m, 4H), 7.32−7.26 (m, 4H), 7.02 (t, J = 7.3 Hz,
2H), 6.62 (d, J = 3.0 Hz, 1H), 4.63 (s, 2H, NH2) ppm. 13C NMR (125
MHz, DMSO-d6) δ: 137.3, 136.8, 133.0, 128.6, 128.3, 124.8, 123.8,
123.0, 122.6, 121.7, 104.6, 104.3 ppm. HRMS (ES) calcd for C16H13N2
[M − H]− 233.1079, found 233.1073.
1
obtained as a dark blue solid. H NMR (600 MHz, CDCl3) δ: 8.08−
3,5-Diphenyl-1H-pyrrol-2-amine, 10-{1-15N1}. Compound 9-
{1-15N1} (100 mg, 0.40 mmol) was dissolved in methanol (11 mL),
and 10% Pd on activated charcoal (21 mg, 0.02 mmol) was added. The
suspension was frozen using liquid nitrogen, and the apparatus was
evacuated then filled with H2 (1 atm). The mixture was allowed to
reach rt and stirred for 2 h. The suspension was filtered over a plug of
Celite, and the filter cake was washed with methanol, carefully avoiding
air to enter in contact with the mixture. The solvent was removed
under vacuo (below 25 °C), yielding a light blue powder (91 mg,
96%): mp 143−145 °C (decomp). 1H NMR (500 MHz, DMSO-d6) δ:
10.44 (dd, J = 94.3, 3.1 Hz, 1H, 15NH coupling), 7.50−7.45 (m, 4H),
7.32−7.26 (m, 4H), 7.05−7.00 (m, 2H), 6.64−6.61 (m, 1H), 4.63 (s,
2H, NH2) ppm. 13C NMR (125 MHz, DMSO-d6) δ: 137.3 (d, J = 16.7
Hz), 136.8 (d, J = 1.7 Hz), 133.0 (d, J = 2.2 Hz), 128.6, 128.3, 124.8,
123.8, 123.0, 122.6 (d, J = 13.7 Hz), 121.7 (d, J = 1.0 Hz), 104.6 (d, J
= 5.1 Hz), 104.3 (d, J = 3.6 Hz) ppm. 15N NMR (60.8 MHz, DMSO-
d6) δ: −240.0 ppm. HRMS (ES) calcd for C16H1314N15N [M − H]−
234.1049, found 234.1047.
8.05 (m, 4H), 7.98−7.95 (m, 4H), 7.57−7.52 (m, 4H), 7.50−7.46 (m,
2H), 7.45−7.41 (m, 4H), 7.38−7.34 (m, 2H), 7.22−7.20 (m, 2H)
ppm. 15N NMR (60.8 MHz, CDCl3) δ: −86.2, −176.2 ppm. ES-MS:
m/z [M + H]+ = 452.2 (100%), 453.2 (37%), 454.2 (8%).
Conversion of 10-{2-15N1} into 2-{15Nmixture} in the Presence
of NH4OAc. A solution of 10-{2-15N1} (40 mg, 0.17 mmol) and
NH4OAc (0.46 g, 6.0 mmol) in EtOH (4.3 mL) was heated under
reflux for 18 h. The precipitate that was formed during the reaction
was collected by filtration, washed with cold EtOH, and dried.
Compound 2-{15Nmixture} (21.9 mg, 57%) was obtained as a dark blue
solid. 1H NMR (600 MHz, CDCl3) δ: 8.08−8.05 (m, 4H), 7.98−7.95
(m, 4H), 7.56−7.52 (m, 4H), 7.49−7.46 (m, 2H), 7.45−7.41 (m, 4H),
7.38−7.34 (m, 2H), 7.21 (s, 2H) ppm. 15N NMR (60.8 MHz, CDCl3)
δ: −86.2, −175.7, −176.2 ppm. ES-MS: m/z [M + H]+ = 450.2 (12%),
451.2 (50%), 452.2 (100%), 453.2 (43%), 454.2 (14%).
Reaction of 8-{1-15N1} and 10 To Form 2-{1-15N1} and 2. A
solution of 8-{1-15N1} (8 mg, 0.036 mmol), 10 (8.5 mg, 0.036 mmol),
and NH4OAc (0.097 g, 1.26 mmol) in EtOH (0.9 mL) was heated
under reflux for 24 h. The precipitate that was formed during the
reaction was collected by filtration, washed with cold EtOH, and dried.
Compound 2-{1-15N1} and unlabeled 2 (8.0 mg, 49%) were obtained
3,5-Diphenyl-1H-pyrrol-2-amine, 10-{2-15N1}. Compound 9-
{2-15N1} (140 mg, 0.56 mmol) was dissolved in methanol (16 mL),
and 10% Pd on activated charcoal (30 mg, 0.028 mmol) was added.
The suspension was frozen using liquid nitrogen, and the apparatus
was evacuated then filled with H2 (1 atm). The mixture was allowed to
reach rt and stirred for 2 h. The suspension was filtered over a plug of
Celite, and the filter cake was washed with methanol, carefully avoiding
air to enter in contact with the mixture. The solvent was removed
under vacuo (below 25 °C), yielding a light blue powder (91 mg,
1
as a dark blue solid. H NMR (600 MHz, CDCl3) δ: 8.08−8.05 (m,
4H), 7.98−7.95 (m, 4H), 7.56−7.52 (m, 4H), 7.49−7.46 (m, 2H),
7.45−7.41 (m, 4H), 7.38−7.35 (m, 2H), 7.22−7.20 (m, 2H) ppm. 15N
NMR (60.8 MHz, CDCl3) δ: −176.3 ppm. ES-MS: m/z [M + H]+ =
450.6 (91%), 451.7 (100%), 452.6 (26%), 453.6 (5%).
Reaction of 8-{1-15N1} and 1 To Form 2-{1-15N1}. A solution of
8-{1-15N1} (10 mg, 0.045 mmol), 1 (12 mg, 0.045 mmol), and
NH4OAc (0.12 g, 1.6 mmol) in EtOH (1.1 mL) was heated under
reflux for 24 h. The precipitate that was formed during the reaction
was collected by filtration, washed with cold EtOH, and dried.
Compound 2-{1-15N1} (6.6 mg, 33%) was obtained as a dark blue
solid. 1H NMR (600 MHz, CDCl3) δ: 8.08−8.05 (m, 4H), 7.98−7.95
(m, 4H), 7.56−7.52 (m, 4H), 7.49−7.46 (m, 2H), 7.45−7.41 (m, 4H),
7.38−7.34 (m, 2H), 7.22−7.20 (m, 2H) ppm. 15N NMR (60.8 MHz,
CDCl3) δ: −176.2 ppm. ES-MS: m/z [M + H]+ = 450.4 (5%), 451.5
(100%), 452.5 (34%), 453.5 (7%).
1
96%). H NMR (500 MHz, DMSO-d6) δ: 10.44 (s, 1H, NH), 7.51−
7.45 (m, 4H), 7.31−7.26 (m, 4H), 7.02 (t, J = 7.3 Hz, 2H), 6.62 (d, J =
3.0 Hz, 1H), 4.63 (d, J = 77.4 Hz, 2H, 15NH2 coupling) ppm. 13C
NMR (125 MHz, DMSO-d6) δ: 137.3 (d, J = 12.2 Hz), 136.8, 133.0,
128.6, 128.3, 124.8, 123.8, 123.0, 122.6 (d, J = 0.9 Hz), 121.7, 104.6
(d, J = 2.1 Hz), 104.3 ppm. 15N NMR (60.8 MHz, DMSO-d6) δ:
−337.1 ppm. HRMS (ES) calcd for C16H1314N15N [M − H]−
234.1049, found 234.1045.
Conversion of 10 into 2 in the Absence of NH4OAc. A
solution of 10 (40 mg, 0.17 mmol) in EtOH (4.3 mL) was heated
under reflux for 18 h. The precipitate that was formed during the
reaction was collected by filtration, washed with cold EtOH, and dried.
Compound 2 (2.9 mg, 8%) was obtained as a dark blue solid. 1H NMR
(400 MHz, CDCl3) δ: 8.06 (d, J = 7.4 Hz, 4H), 7.96 (d, J = 7.5 Hz,
4H), 7.57−7.51 (m, 4H), 7.50−7.41 (m, 6H), 7.39−7.34 (m, 2H),
7.21 (s, 2H) ppm. ES-MS: m/z [M + H]+ = 450 (100%), 451 (36%),
452 (6%).
ASSOCIATED CONTENT
■
S
* Supporting Information
ESI-MS/MS of 2-{1-15N1}, 2-{6-15N1}. H, 13C, and 15N NMR
1
and ESI-MS of all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
Conversion of 10 into 2 in the Presence of NH4OAc. A
solution of 10 (40 mg, 0.17 mmol) and NH4OAc (0.46 g, 6.0 mmol)
in EtOH (4.3 mL) was heated under reflux for 18 h. The precipitate
that was formed during the reaction was collected by filtration, washed
with cold EtOH, and dried. Compound 2 (21 mg, 56%) was obtained
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: donal.f.oshea@ucd.ie.
Notes
1
as a dark blue solid. H NMR (400 MHz, CDCl3) δ: 8.06 (d, J = 7.4
The authors declare no competing financial interest.
Hz, 4H), 7.96 (d, J = 7.5 Hz, 4H), 7.57−7.51 (m, 4H), 7.50−7.41 (m,
6H), 7.39−7.34 (m, 2H), 7.21 (s, 2H) ppm. ES-MS: m/z [M + H]+ =
450 (100%), 451 (36%), 452 (6%).
ACKNOWLEDGMENTS
■
Conversion of 10-{1-15N1} into 2-{1-15N1} in the Absence of
NH4OAc. A solution of 10-{1-15N1} (40 mg, 0.17 mmol) in EtOH
(4.3 mL) was heated under reflux for 18 h. The precipitate that was
formed during the reaction was collected by filtration, washed with
cold EtOH, and dried. Compound 2-{1-15N1} (3.4 mg, 9%) was
The authors are grateful to Science Foundation Ireland for
funding. M.G. thanks Irish Research Council for a Ph.D.
fellowship.
1
REFERENCES
obtained as a dark blue solid. H NMR (600 MHz, CDCl3) δ: 8.08−
■
8.05 (m, 4H), 7.98−7.95 (m, 4H), 7.56−7.52 (m, 4H), 7.49−7.46 (m,
2H), 7.45−7.41 (m, 4H), 7.38−7.34 (m, 2H), 7.22−7.20 (m, 2H)
ppm. 15N NMR (60.8 MHz, CDCl3) δ: −176.2 ppm. ES-MS: m/z [M
+ H]+ = 451.2 (100%), 452.2 (39%), 453.2 (10%).
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dx.doi.org/10.1021/jo301972w | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
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