Exploring the reactivity of 1,5-disubstituted sulfonyl-triazoles: Thermolysis and Rh(II)-catalyzed synthesis of α-sulfonyl nitriles This article is dedicated to Professor Paul Wender for both his creative contributions to synthetic organic chemistry and u

Article abstract of DOI:10.1016/j.tet.2013.05.048

The reactivity of a series of 1,5-disubstituted sulfonyl-triazoles was explored using either thermolytic or metal-catalyzed conditions. Both the thermolysis and the Rh(II)-catalyzed reactions led to the synthesis of α-sulfonyl-nitriles, which presumably o

Full text of DOI:10.1016/j.tet.2013.05.048

Tetrahedron xxx (2013) 1e7
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journal homepage: www.elsevier.com/locate/tet
Exploring the reactivity of 1,5-disubstituted sulfonyl-triazoles:
thermolysis and Rh(II)-catalyzed synthesis of
a-sulfonyl nitriles
*
~
Maria Elena Meza-Avina, Mudita Kishor Patel, Mitchell P. Croatt
Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, 435 Sullivan Science Building, PO Box 26170, Greensboro, NC
27402, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The reactivity of a series of 1,5-disubstituted sulfonyl-triazoles was explored using either thermolytic or
metal-catalyzed conditions. Both the thermolysis and the Rh(II)-catalyzed reactions led to the synthesis
of a-sulfonyl-nitriles, which presumably occurred through a carbene or carbenoid mechanism. The re-
activity of the carbenes and carbenoids resulting from the loss of dinitrogen from the 1,5-disubstituted
sulfonyl-triazoles were different from those of the previously explored 1,4-disubstituted sulfonyl-
triazoles. It was observed by NMR that the Rh(II)-catalyst coordinates strongly but reversibly with the
1,5-disubstituted sulfonyl-triazoles. Other catalysts, including both Brønsted and Lewis acids, were found
to catalyze this transformation, although less efficiently compared to neat thermolysis or Rh(II)-catalyzed
conditions. These data illustrate both the unique nature of 1,5-disubstituted sulfonyl-triazoles and po-
tential future avenues for their utilization.
Received 7 March 2013
Received in revised form 11 May 2013
Accepted 13 May 2013
Available online xxx
This article is dedicated to Professor Paul
Wender for both his creative contributions
to synthetic organic chemistry and untiring
mentorship
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Triazoles
Thermolysis
Rhodium
Nitriles
Carbenes
1. Introduction
The use of 1,2,3-triazoles, and heterocycles in general, as
building blocks in medicinal chemistry has led to a broad variety of
synthetic methods to obtain them.1 For example, triazoles have
been used to link together components, often using a copper(I)
catalyst in a so-called ‘Click Reaction’, and they are often utilized as
a bioisostere of esters and amides.2 The methods to synthesize 1,4-
disubstituted triazoles are numerous, but only recently our group
Scheme 1. Synthesis of 1,5-disubstituted sulfonyl-triazoles.
Although methods to form 1,4-disubstituted triazoles have been
reported for quite some time, it was only relatively recent that ef-
ficient methods to make 1,4-disubstituted sulfonyl-triazoles was
reported.6 A primary reason for this is that these sulfonyl-triazoles
reported
a method to selectively and efficiently form 1,5-
disubstituted sulfonyl-triazoles3 during our quest to form cyano-
carbenes from alkynes and azides.4 Other researchers had pre-
viously disclosed similar reactions to form these triazoles,5
however, since our report was the first extensive study to form
1,2,3-triazoles with this type of substitution, we had the opportu-
nity to explore the reactivity of this unique class of triazoles. Herein,
we report the reactivity of these compounds under both thermo-
lytic and metal-catalyzed conditions and contrast the reactivity
with that of the previously reported 1,4-disubstituted sulfonyl-
triazoles (Scheme 1).
(5) are often in equilibrium with the opened form, an
a-diazo-
sulfonylimine (6; Scheme 2).7 Because of this, many groups have
exploited this equilibrium by the addition of Rh(II) catalysts to form
a carbenoid species (7) that can be reacted in a diverse set of re-
actions. These reactions have been extensively studied by the
groups of Fokin, Gevorgyan, and Murakami.8 As is illustrated in
Scheme 2, the rhodium carbenoid (7) can be reacted with nitriles,
alkynes, aldehydes, imines, alcohols, alkenes, alkanes, boronic
acids, or water to form sulfonyl-substituted imidazoles,8a pyrro-
les,8d dihydrooxazoles,8e imidazoles,8e
cyclopropyl carboxaldehydes,8b alkylated sulfonylaldimines,8c ary-
lated sulfonylenamines,8i and -sulfonamido ketones,8h re-
spectively. Based on this wealth of interesting reactivities for 1,4-
b
-sulfonamido enones,8g,h
a
* Corresponding author. Tel.: þ1 336 334 3785; fax: þ1 336 334 5402; e-mail
address: mpcroatt@uncg.edu (M.P. Croatt).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.05.048
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M.E. Meza-Avina et al. / Tetrahedron xxx (2013) 1e7
2
disubstituted sulfonyl-triazoles, we decided that it would be in-
teresting to examine the reactivity of 1,5-disubstiuted sulfonyl-
triazoles. Importantly, we wanted to determine if their reactivity
would mimic or even match that of 1,4-disubstituted sulfonyl-
triazoles or if they would establish their own unique reactivity.
reactions and thermolytic conditions in the absence of a transition
metal catalyst. It was hypothesized that the 1,5-isomers (2) will
provide access to unique reactivity since extrusion of N2 yields
a primary carbene or carbenoid species (3) instead of the secondary
benzylic species found by Fokin and others (7).8
2. Results and discussion
2.1. Synthesis of 1,5-disubstituted sulfonyl-triazoles
Following the general procedure previously reported, 10 triazoles
(five new and five previously reported) were synthesized (Scheme 4).3
Isomerization of the 1,5-isomer to the 1,4-isomer is observed after
a short period of time, so the compounds were prepared no more than
1 or 2 days in advance. The compounds synthesized used four dif-
ferent sulfonyl groups and either electron-rich or electron-poor aryl
alkynes. Aliphatic alkynes were also used successfully for the syn-
thesis of 1,5-disubstituted sulfonyl-triazoles,3 but they were not suc-
cessful in the subsequent reactions described in this manuscript.
Trisubstituted triazoles were also synthesized by trapping the initially
formed triazole anion with an electrophile, however, these triazoles
also did not undergo the reactions reported herein. It should be noted
that even though the Dimroth rearrangement of triazoles with
electron-withdrawing groups like p-toluenesulfonyl, at the N1 posi-
tion has been reported,7 we were not able to observe any of the ring-
open structure. This result is in agreement with the observations for
related compounds.10
Scheme 2. Reactions of 1,4-disubstituted sulfonyl-triazoles.8
During ourcharacterization of 1,5-disubstituted sulfonyl-triazoles,
two interesting observations were made. First, the ring-open form of
the triazole was not observed, which is in contrast to the 1,4-sulfonyl-
triazoles (5 in equilibrium with 6; Scheme 2).8 Second, while
obtaining the melting points of some products, extrusion of N2 was
occurring prior to or simultaneous with melting. For mechanistic
reactions, it should be noted that there are reports of vacuum pyrol-
ysis9 at 400e500 ꢀC of trisubstituted triazoles (17 and 18, Scheme 3).
In this report, they determine that both triazoles yielded the same
products (20e24), and in the equivalent proportions, so they pro-
posed the formation of an identical azirine (19) for both triazoles. The
authors hypothesize that the reaction is occurring by a diradical
mechanism. The pyrolysis with the sulfonyl-triazoles described
herein occurs at temperatures well below 400e500 ꢀC so it is likely
that a different mechanism could be occurring.
Scheme 4. Synthesis of 1,5-disubstituted sulfonyl-triazoles with isolated yields.
2.2. Thermolysis
The first substrate that we chose to analyze was triazole 26b
because it was found to decompose prior to melting in our prior
report.3 When this compound was heated in an oil bath at 123 ꢀC,
the solid immediately and simultaneously melted while extruding
gas. The mixture turned from light yellow to orange and then
brown within 5 min at which point no more gas was observed
bubbling out the sample. The thick oil was dissolved in CDCl3, and
the 1H NMR had a new signal at 5.06 ppm and the aromatic proton
of the triazole had disappeared. Analysis by HRMS indicated a loss
Scheme 3. Vacuum pyrolysis of trisubstituted triazoles.9
In theory, the sulfonyl-triazoles examined in the present study
(2, Scheme 1) could lose dinitrogen, form an azirine similar to
azirine 19, and then react similar to the prior work of Scheme 2. To
explore the reactivity of a series of 1,5-disubstituted sulfonyl-
triazoles, it was decided to examine both Rh(II) catalyzed
of dinitrogen and the structure was identified to be a-nitrile sulfone
27b as the major product (Scheme 5). Although this was not an
anticipated product, it is a known compound and the 1H NMR was
found to be identical.11
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M.E. Meza-Avina et al. / Tetrahedron xxx (2013) 1e7
3
Table 1
Qualitative Rh(II)-catalyzed optimization
Entry
1
Rh2(OAc)4 mol %
10 mol %
Solvent/reagent
Temp/time
140 ꢀC/15 min
Producta
CHCl3/CH3CN
(3 equiv)
CH3CN
CHCl3
CHCl3
27b
2
3
4
5
6
10 mol %
8 mol %
0 mol %
8 mol %
10 mol %
140 ꢀC/15 min
140 ꢀC/15 min
140 ꢀC/15 min
100 ꢀC/60 min
100 ꢀC/15 min
27b
27b
26b
27b
CHCl3
CHCl3/CH3CN
(3 equiv)
CHCl3/CH3CN
(3 equiv)
CHCl3
27b, 28, 29
7
8
10 mol %
80 ꢀC/15 min
50 ꢀC/15 min
rt/3 h
29b
29
1, 3, 5, 10, 25,
50, 100 mol %
0.5, 8, 10 mol %
9
CHCl3
29
a
Main product based on crude 1H NMR.
Trace amounts of 27 and 28 were observed.
b
Scheme 5. Thermolysis of 1,5-disubstituted sulfonyl-triazoles with temperatures and
isolated yields.
nitrile, and another product that later we identified as the Rh
complex of the 1,5-isomer (29) were observed.
Interestingly, when the catalyst loading was varied from 1 to
100 mol % at 50 ꢀC (Table 1, entry 8 and Fig. 1) and 0.5, 8 and
10 mol % at room temperature for 3 h (entry 9), a Rh complex was
observed (29). As is illustrated in Fig. 1, the vinylic proton on po-
sition 4 in the triazole is shifted to low field as the amount of cat-
alyst was increased. Also, the other signals shift and the two
doublets that are overlapped at 7.26e7.33 ppm get resolved to two
doublets at 7.38 ppm and 7.27 ppm. With all of these reactions
where the triazole is complexed with the catalyst, starting material
(26b) is recovered when purified by silica gel chromatography.
For the thermolysis of the triazoles, first the melting points or
decomposition temperatures were determined, and then a tem-
perature w2e5 ꢀC (decomp.) or w20e50 ꢀC (mp) higher was used.
This is because we observed that, in general, a very short reaction
time was required with the temperature high enough to undergo
the N2 extrusion. If the temperature was not high enough, isom-
erization of the 1,5-isomer to the 1,4-isomer was observed as the
major product. Interestingly, the 1,4-isomer was not as reactive
with these conditions for at least one substrate. For the series with
the p-nitrophenylsulfonyl group in the 1-position (27def), the re-
actions were very fast (around 1 min), and the yields were low with
formation of insoluble material. The crude 1H NMRs of the ther-
0.6
0.5
0.4
0.3
0.2
molysis illustrated the a-nitrile sulfone as the main product, how-
ever, the bulk of the mass balance was insoluble, black solids.
0.1
0
-0.1
-0.2
-0.3
-0.4
-0.5
-0.6
-0.7
-0.8
-0.9
-1.0
-1.1
-1.2
-1.3
-1.4
2.3. Rh(II)-catalyzed reactions
Taking into consideration the reports on the reactivity of the 1,4-
triazoles with Rh(II), we decided to follow a recently reported
procedure described by Fokin8a where they use 0.5 mol % of a Rh(II)
catalyst and 3 equiv of a nitrile in chloroform under microwave
conditions for 15 min. The only alteration that we made was using
between 8 and 10 mol % of catalyst (Table 1). We observed the same
a
-sulfonyl nitriles as previously discussed when heated without
8.4
8.3
8.2
8.1
8.0
7.9
7.8
7.7
7.6
7.5
7.4
7.3
7.2
7.1
7.0
6.9
a catalyst (entry 1), so we decided to increase the amount of ace-
tonitrile and used it as the solvent (entry 2). The product was again
the sulfonyl-nitrile, which was also formed using only chloroform
as a solvent (entry 3). To establish if the catalyst has any effect in
this outcome, the triazole was dissolved in chloroform and heated
in the microwave to 140 ꢀC for 15 min in the absence of catalyst
(entry 4). This time only starting material was recovered.
Chemical Shift (ppm)
Fig. 1. Observation of catalyst coordination with catalyst loadings from 0 mol % (top) to
100 mol % (bottom) as determined by 1H NMR.
Since formation of the sulfonyl-nitrile from the triazoles oc-
curred under both thermal conditions in the absence of solvent and
with the addition of a Rh(II)-catalyst, we decided to try other ad-
ditives including HCl$Et2O, AgSbF6, TFA, and CuI. The vials were
heated in the microwave initially for 15 min at 50 ꢀC and then
subjected to further heating after an aliquot was removed for
analysis. HCl$Et2O at 50 ꢀC/15 min and 140 ꢀC/15 min (Table 2,
The temperature of the reaction was lowered to 100 ꢀC and, not
surprisingly, a longer reaction time was required to fully convert
the triazole to sulfonyl nitrile 27b (entry 5). When the reaction at
either 100 ꢀC or 80 ꢀC was stopped before the reaction was com-
plete (entries 6 and 7), a mixture of the 1,4-isomer, the sulfonyl
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Table 2
Qualitative catalyst screening
the sulfonyl nitriles were more efficient using a Rh(II)-catalyst, but
in other cases (27b, c, f, h, and j) heating without solvent was ac-
tually more efficient. The yields for these metal-catalyzed trans-
formation varied widely, from 2% to 57%, and do not appear to
follow any general trend using either sterics or electronics of either
of the aryl-groups.
2.4. Discussion
Entry
Catalyst
Temp/time
Producta
An important observation from this study is that the 1,5-
disubstituted sulfonyl-triazoles have different reactivity compared
to the 1,4-disubstituted sulfonyl-triazoles. Both triazoles react to
extrude dinitrogen, however, the subsequent reactions and rear-
rangements are remarkably different. This could be due to both
steric and electronic factors since the carbene or carbenoid in this
case is primary and not benzylic. It should also be noted that when
the triazoles were either trisubstituted or substituted with an alkyl-
chain at carbon 5 instead of an aryl-group, the reactions described
herein do not proceed. Instead the triazoles slowly decompose to
a complex mixture of unidentified products.
1
2
3
4
5
6
7
8
9
10
HCl$Et2O, 10 mol %
HCl$Et2O, 10 mol %
HCl$Et2O, 10 mol %
AgSbF6, 13 mol %
AgSbF6, 13 mol %
TFA, 10 mol %
TFA, 10 mol %
CuI, 10 mol %
CuI, 10 mol %
CuI, 10 mol %
50 ꢀC/15 min
140 ꢀC/15 min
140 ꢀC/45 min
50 ꢀC/15 min
115 ꢀC/4 h
50 ꢀC/15 min
140 ꢀC/15 min
50 ꢀC/15 min
140 ꢀC/15 min
140 ꢀC/1 h
26b
26b
27bb
26b, 28
27bb
26b, 28
27bb
26b
26b, 28b
27bb
a
Main product based on crude 1H NMR.
Reaction was inefficient and had many other side products.
b
In Scheme 7, we propose a reaction mechanism that leads to the
products that we observe, both for the metal-catalyzed route and
the metal-free system. In either reaction, N2 is initially released and
a carbene (A) or carbenoid species (D) is formed. In the metal-free
system, the next step involves a 1,3-sulfonyl shift, either by the
intermediacy of a cyclic system (B) or directly by a sigmatropic
rearrangement. Zwitterion C is then set up for a shifting of the aryl
group to form the nitrile. The metal catalyzed pathway is similar
since the sulfonyl group is transferred from the nitrogen to the
carbon, a carbenoid is converted to a nitrenoid (which is similar to
a resonance form of zwitterion C), and the aryl-group is then mi-
grated to allow for formation of a nitrile. Attempts were made to
trap the carbenes using allyl benzene, but in all cases sulfonyl-
nitriles were observed and products resulting from cyclo-
propanation or CeH insertion were not observed. This is likely due
to the more rapid intramolecular reactions.
entries 1 and 2) and CuI at 50 ꢀC/15 min (entry 8) had no reaction by
1H NMR. Crude 1H NMR of the reaction with AgSbF6 at 50 ꢀC/15 min
(entry 4), TFA at 50 ꢀC/15 min (entry 6), and CuI at 140 ꢀC/15 min
(entry 9) showed a mixture of 1,5- and 1,4-sulfonyl triazole isomers
26b and 28. The reactions with HCl$Et2O at 140 ꢀC/45 min (entry 3),
AgSbF6 at 115 ꢀC/4 h (entry 5), TFA at 140 ꢀC/15 min (entry 7) and
CuI at 140 ꢀC/1 h (entry 10) led to the formation of
a-nitrile sulfone
27b as the major product in the crude 1H NMR. It is important to
mention that, compared to the reactions where we use the Rh(II)
catalyst, all of the reactions with additives that produced the sul-
fonyl nitrile had crude NMR’s with major amounts of impurities.
Since the reactions were more efficient with the Rh2(OAc)4 as
the catalyst compared to other catalysts, the entire series of 1,5-
disubstituted sulfonyl-triazoles were studied with these condi-
tions (Scheme 6). In some cases (27a, c, and i) the reactions to form
Scheme 7. Proposed mechanism.
Of mechanistic significance with this reaction, the products are
dissimilar to those of 1,4-disubstituted sulfonyl-triazoles even
though it is likely that a sulfonylimine with a carbene or carbenoid
species adjacent is formed in both cases. A rationalization of this
difference is that the sulfonyl group can be near the carbene or
carbenoid species in this case, whereas the prior systems (7) would
Scheme 6. Rh(II)-catalyzed formation of sulfonyl-nitriles with conditions and isolated
yields.
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M.E. Meza-Avina et al. / Tetrahedron xxx (2013) 1e7
5
strongly prefer to have the sulfonyl group away from the carbene or
carbenoid for steric reasons.
d
8.39 (d, J¼9.2 Hz, 2H), 8.10 (d, J¼9.2 Hz, 2H), 7.79 (d, J¼8.6 Hz, 2H),
7.68 (s, 1H), 7.58 (d, J¼8.6 Hz, 2H). 13C NMR (125 MHz) 151.8, 141.9,
138.8, 134.8, 132.9 (q, J¼33.4 Hz, 1C), 130.7 (2C), 130.5 (2C), 128.7,
125.7 (q, J¼3.6 Hz, 2C), 125.0 (2C), 123.7 (q, J¼271.0 Hz, 1C). IR 3105,
1531, 1407, 1344, 1329, 1195, 1169, 1158, 1117, 1103, 1069, 959, 846,
747, 738, 676, 628, 614, 567 cmꢁ1. HRMS [MþH]þ C15H10N4O4SF3
calculated: 399.03749; found: 399.03665.
3. Conclusion
A group of 1,5-disubstituted sulfonyl-triazoles were synthesized
and all of them reacted under thermolytic and Rh(II)-catalyzed
conditions to provide a-sulfonyl nitrile products. These products
are different from the products of similar reactions with the more
commonly explored 1,4-disubstituted sulfonyl-triazoles. Under
Rh(II)-catalyzed conditions a coordination to the catalyst was ob-
served and the reaction also took place with the addition of other
catalysts. The interesting reactivities of 1,5-disubstituted sulfonyl-
triazoles and sulfonyl-nitriles are currently being explored in our
group.
4.2.3. 1-(4-Bromobenzenesulfonyl)-5-phenyl-1,2,3-triazole
(26h). Yellow solid (292 mg, 70%); 1H NMR (500 MHz)
d 7.64e7.62
(m, 4H), 7.60 (s, 1H), 7.56e7.53 (m, 1H), 7.49e7.46 (m, 2H), 7.37 (d,
J¼7.5 Hz, 2H). 13C NMR (125 MHz) 139.9, 135.6, 134.5, 133.1 (2C),
131.5, 130.6, 130.3 (2C), 130.2 (2C), 128.6 (2C), 125.2. IR 3079, 3058,
1570, 1481, 1393, 1241, 1195, 1167, 1069, 976, 957, 820, 744, 688, 604,
573 cmꢁ1. HRMS [MþH]þ C14H11N3O2S79Br calculated: 363.97554;
found: 363.97488; C14H11N3O2S81Br calculated: 365.97349; found:
365.97284.
4. Experimental
4.1. General information
4.2.4. 1-(4-Bromobenzenesulfonyl)-5-(4-methoxyphenyl)-1,2,3-
triazole (26i). White solid (180 mg, 89%); 1H NMR (500 MHz)
The anhydrous reactions were performed in oven-dried glass-
ware under nitrogen atmosphere. Unless noted, all solvents and
reagents were obtained from commercial sources and used without
further purification. Anhydrous solvents were dried following
standard procedure, reaction progress was monitored by TLC (Silica
gel 60 F254) using glass plates visualized with UV light and potas-
d
7.65e7.61 (m, 4H), 7.55 (s, 1H), 7.31 (d, J¼9.0 Hz, 2H), 6.99 (d,
J¼9.0 Hz, 2H), 3.89 (s, 3H). 13C NMR (125 MHz) 161.4, 139.9, 135.7,
134.4, 133.0 (2C), 131.7 (2C), 131.4, 130.2 (2C), 117.0, 114.0 (2C), 55.6.
IR 3144, 3086, 2970, 2906, 1613, 1569, 1489, 1469, 1393, 1255,
1195, 1170, 1026, 977, 955, 854, 829, 817, 745, 619, 601, 571 cmꢁ1
.
HRMS [MþH]þ C15H13N3O3S79Br calculated: 393.98610; found:
sium permanganate stain.12 Chromatographic purification was
393.98553;
395.98321.
C
15H13N3O3S81Br calculated: 395.98405; found:
ꢀ
performed using silica gel (60 A, 32e63
m
m) or BiotageÒ SP1Ô. The
microwave reactions were performed on a BiotageÒ Initiator Mi-
crowave Synthesizer. NMR spectra were recorded in CDCl3 using
a Bruker AVANCE DRX 300 spectrometer (300 MHz for 1H), JEOL
ECA spectrometer (500 MHz for 1H and 125 MHz for 13C), or Agilent
Technologies Spectrometer (700 MHz for 1H and 176 MHz for 13C).
4.2.5. 1-(4-Bromobenzenesulfonyl)-5-(4-trifluoromethylphenyl)-
1,2,3-triazole (26j). White solid (65 mg, 79%); 1H NMR (700 MHz)
d
7.76 (d, J¼8.0 Hz, 2H), 7.72e7.67 (m, 4H), 7.66 (s, 1H), 7.56 (d,
J¼8.0 Hz, 2H). 13C NMR (176 MHz) 138.4, 135.5, 134.7, 133.3 (2C),
132.6 (q, J¼33.4 Hz, 1C), 131.9, 130.7 (2C), 130.3 (2C), 129.1, 125.5 (q,
J¼4.1 Hz, 2C), 124.0 (q, J¼271.0 Hz, 1C). IR 1610, 1574, 1534, 1397,
Chemical shifts reported in
d parts per million using tetrame-
thylsilane as reference for the 1H NMR and the residual solvent
peak for 13C (77 ppm). The abbreviations used to describe peak
splitting patterns are: s¼singlet, d¼doublet, t¼triplet, sept¼septet,
m¼multiplet. Coupling constants, J, are reported in hertz (Hz). IR
spectra were obtained with Perkin Elmer FTIR Spectrometer One
and Spectrometer 65 with ATR sampling accessories. Frequencies
are in cmꢁ1. High Resolution Mass Spectra were acquired at the
Triad Mass Spectrometry Laboratory at the University of North
Carolina at Greensboro on a ThermoFisher Scientific LTQ Orbitrap
XL MS system using APCI or ESI in positive or negative mode or at
the David H. Murdock Research Institute on a Waters Qtof MS
system using ESI in negative mode.
1324, 1237, 1191, 1169, 1123, 1065, 1001, 826, 744, 608, 575 cmꢁ1
.
HRMS [MþH]þ C15H10N3O2SF379Br calculated: 431.96237; found:
431.96298;
433.96048.
C
15H10N3O2SF381Br calculated: 433.96032; found:
4.3. General method for the thermolysis of 1,5-triazole
Neat triazole (0.12e0.36 mmol) in a vial is put in an oil bath and
heated until gas evolution occurs. It is more efficient if this tem-
perature is w10 ꢀC higher than the initial point that melting occurs.
There is a color change, from yellow to dark brown or black when
the reaction ended and no more gas is evolved. If the melting point
is known, the pyrolysis is performed at least 20e40 ꢀC higher than
the melting point temperature. In all the experiments, the best
results were obtained when the reaction lasted between 3 and
6 min. If the time is longer and the temperature is not high enough,
a major product is the respective 1,4-triazole. For all the triazoles
synthesized from 4-nitro-benzene-sulfonyl azide, the yields were
very low with insoluble material and yellow-orange gas evolved.
The solvent was evaporated and the product was isolated using
column chromatography.
4.2. Synthesis of 1,5-disubstituted sulfonyl-triazoles
All the triazoles were synthesized following the method pre-
viously reported3 by our research group and the characterization of
triazoles 26aed and 26g were reported in Ref. 3. Spectroscopy data
for 26eef and 26hej are reported below.
4.2.1. 1-(4-Nitrobenzenesulfonyl)-5-(4-methoxyphenyl)-1,2,3-
triazole (26e). Yellow solid (404 mg, 85%); 1H NMR (500 MHz)
d
8.33 (d, J¼9.2 Hz, 2H), 8.00 (d, J¼9.2 Hz, 2H), 7.57 (s, 1H), 7.33 (d,
J¼8.6 Hz, 2H), 7.00 (d, J¼8.6 Hz, 2H), 3.93 (s, 3H). 13C NMR
(125 MHz) 161.6, 151.6, 142.2, 140.3, 134.4, 131.7 (2C), 130.2 (2C),
124.8 (2C), 116.6, 114.2 (2C), 55.7. IR 3068, 2970, 1608, 1531, 1493,
1404, 1395, 1347, 1308, 1288, 1251, 1190, 1178, 1169, 1084, 1026, 954,
854, 742, 676, 619, 605, 575, 548 cmꢁ1. HRMS [MþH]þ C15H13N4O5S
calculated: 361.06012; found: 361.05936.
4.4. General method for Rh(II) catalyzed microwave reactions
of 1,5-triazole
The triazole (0.041e0.41 mmol) was dissolved in chloroform
(0.03 M) and 9 mol % of Rh2(OAc)4 was added, heated in the mi-
crowave at 140 ꢀC for 1 or 15 min or 190 ꢀC for 1 or 15 min. The
solvent was evaporated and the product was isolated using column
chromatography.
4.2.2. 1-(4-Nitrobenzenesulfonyl)-5-(4-trifluoromethylphenyl)-1,2,3-
triazole (26f). Yellow solid (241 mg, 46%); 1H NMR (500 MHz)
~
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M.E. Meza-Avina et al. / Tetrahedron xxx (2013) 1e7
6
4.5. Characterization of
a
-sulfonyl nitriles
calculated: 333.953735; found: 333.95358; C14H9NO2S81Br calcu-
lated: 335.951689; found: 335.95175.
The characterization of compounds 27a and b were reported in
Ref. 11. Spectroscopy data for 27cej are reported below.
4.5.7. (4-Methoxyphenyl)-(4-bromobenzenesulfonyl)-acetonitrile
(27i). Yellow solid (thermolysis: 160 ꢀC, 33 mg, 34%; Rh cat: 140 ꢀC/
4.5.1. (4-Trifluoromethylphenyl)-(4-methylbenzenesulfonyl)-acetoni-
trile (27c). White solid (thermolysis: 165 ꢀC, 40 mg, 42%; Rh cat:
15 min, 68 mg, 44%); 1H NMR (500 MHz)
d
7.68 (d, J¼8.6 Hz, 2H), 7.57
(d, J¼9.2 Hz, 2H), 7.20 (d, J¼8.6 Hz, 2H), 6.90 (d, J¼9.2 Hz, 2H), 5.09 (s,
1H), 3.84 (s, 3H). 13C NMR (125 MHz) 161.6, 133.3, 132.8 (2C), 131.7
(2C), 131.3 (2C), 131.2, 116.7, 114.8 (2C), 113.6, 62.7, 55.7. IR 3089,
2929, 2840,1730,1608,1571,1510,1468,1389,1335,1307,1253,1177,
1153, 1081, 1067, 1029, 1009, 825, 776, 739, 616, 574 cmꢁ1. HRMS
[MꢁH]ꢁ C15H11NO3S79Br calculated: 363.9643; found: 363.9659;
190 ꢀC/1 min, 3.1 mg, 2.3%); 1H NMR (500 MHz)
d 7.68e7.62 (m,
4H), 7.46 (d, J¼8.0 Hz, 2H), 7.36 (d, J¼8.0 Hz, 2H), 5.17 (s,1H), 2.49 (s,
3H). 13C NMR (125 MHz) 147.5, 132.8 (q, J¼33.4 Hz, 1C), 131.3, 130.5
(2C), 130.3 (4C), 129.6, 126.2 (q, J¼3.6 Hz, 2C), 123.7 (q, J¼271.1 Hz,
1C), 113.2, 62.8, 22.1. IR 292, 1594, 1323, 1164, 1149, 1116, 1068, 1018,
849, 810, 720, 678, 644, 577 cmꢁ1. HRMS [MþH]þ C16H13NO2SF3
calculated: 340.06191; found: 340.06164.
C
15H11NO3S81Br calculated: 365.9628; found: 365.9643.
4.5.8. (4-Trifluoromethylphenyl)-(4-bromobenzenesulfonyl)-acetoni-
trile (27j). Yellow solid (thermolysis: 160 ꢀC, 41 mg, 41%; Rh cat:
4.5.2. Phenyl-(4-nitrobenzenesulfonyl)-acetonitrile (27d). Yellow
solid (thermolysis: 127 ꢀC, 16.4 mg, 27%; Rh cat: 140 ꢀC/1 min,
160 ꢀC/15 min, 9 mg, 19%); 1H NMR (500 MHz)
d
7.73 (d, J¼8.6 Hz,
18 mg, 24%); 1H NMR (500 MHz)
d
8.36 (d, J¼8.6 Hz, 2H), 7.91 (d,
2H), 7.70 (d, J¼8.6 Hz, 2H), 7.62 (d, J¼8.6 Hz, 2H), 7.49 (d, J¼8.6 Hz,
2H), 5.18 (s, 1H). 13C NMR (125 MHz) 133.0 (q, J¼32.4 Hz, 1C), 133.1
(2C),131.9,131.7 (2C),130.5 (2C),129.0,126.4 (q, J¼3.6 Hz, 2C),124.8,
123.6 (q, J¼270.0 Hz,1C),113.0, 62.7. IR 3092, 2930,1572,1391,1322,
1161, 1129, 1068, 1019, 1010, 851, 824, 741, 606 cmꢁ1. HRMS [MþH]þ
C15H10NO2S79BrF3 calculated: 403.95677; found: 403.95630;
J¼8.6 Hz, 2H), 7.52e7.49 (m, 1H), 7.43e7.40 (m, 2H), 7.31 (d,
J¼8.1 Hz, 2H), 5.23 (s, 1H). 13C NMR (125 MHz) 151.8, 139.7, 131.9
(2C), 131.2, 129.9 (2C), 129.6 (2C), 124.6, 124.4 (2C), 113.0, 63.4. IR
3104, 2928, 1606, 1533, 1456, 1348, 1313, 1158, 1081, 856, 794, 749,
737, 695, 681, 592, 580 cmꢁ1. HRMS [MꢁH]ꢁ C14H9N2O4S calcu-
lated: 301.0283; found: 301.0297.
C
15H10NO2S81BrF3 calculated: 405.95473; found: 405.95423.
4.5.3. (4-Methoxyphenyl)-(4-nitrobenzenesulfonyl)-acetonitrile
Acknowledgements
(27e). Yellow solid (thermolysis: 148 ꢀC, 10 mg, 9%; Rh cat: 140 ꢀC/
15 min, 20 mg, 57%); 1H NMR (500 MHz)
d
8.37 (d, J¼9.2 Hz, 2H),
Funding for this project from The University of North Carolina at
Greensboro and ACS-PRF (52488-DNI1) grant is gratefully ac-
knowledged. The authors thank Dr. Franklin J. Moy (UNCG) for
assisting with analysis of NMR data and Dr. Brandie Ehrmann
(UNCG) for acquisition of the high resolution mass spectrometry
data at the Triad Mass Spectrometry Laboratory at the University of
North Carolina at Greensboro.
7.92 (d, J¼9.2 Hz, 2H), 7.21 (d, J¼8.6 Hz, 2H), 6.91 (d, J¼8.6 Hz, 2H),
5.17 (s, 1H), 3.84 (s, 3H). 13C NMR (125 MHz) 161.9, 151.7, 139.8, 131.9
(2C), 131.3 (2C), 124.4 (2C), 116.0, 115.0 (2C), 113.2, 62.9, 55.7. IR
2954, 2928, 1711, 1598, 1457, 1425, 1361, 1317, 1260, 1221, 1194, 1155,
774, 694, 667, 582 cmꢁ1. HRMS [MꢁH]ꢁ C15H11N2O5S calculated:
331.0389; found: 331.0395.
4.5.4. (4-Trifluoromethylphenyl)-(4-nitrobenzenesulfonyl)-acetoni-
trile (27f). Yellow solid (thermolysis: 152 ꢀC, 16.4 mg, 26%; Rh cat:
Supplementary data
190 ꢀC/1 min, 4.3 mg, 13%); 1H NMR (500 MHz)
d
8.43 (d, J¼8.6 Hz,
Copies of 1H NMR and 13C NMR spectra for compounds 26e, 26f,
26hej, and 27cej are available. Supplementary data related to this
article can be found at http://dx.doi.org/10.1016/j.tet.2013.05.048.
2H), 8.02 (d, J¼8.6 Hz, 2H), 7.73 (d, J¼8.0 Hz, 2H), 7.53 (d, J¼8.0 Hz,
2H), 5.26 (s, 1H). 13C NMR (176 MHz) 152.1, 139.7, 133.5 (q,
J¼33.4 Hz, 1C), 131.9 (2C), 130.6 (2C), 128.3, 126.7 (q, J¼3.52 Hz, 2C),
124.8 (2C), 123.5 (q, J¼272.8 Hz, 1C), 112.6, 62.8. IR 3110, 2936, 1531,
References and notes
1348, 1322, 1151, 1126, 1067, 848, 747, 734, 678, 668, 610, 563 cmꢁ1
.
HRMS [MꢁH]ꢁ C15H10N2O4SF3 calculated: 369.01624; found:
1. For a set of reviews in this area, see the themed issue: Chem. Soc. Rev. 2010, 39,
1221e1408.
369.01439.
2. (a) Patani, G. A.; LaVoie, E. J. Chem. Rev. 1996, 96, 3147e3176; (b) Odlo, K.;
Fournier-Dit-Chabert, J.; Ducki, S.; Gani, O. A. B. S. M.; Sylte, I.; Hansen, T. V.
Bioorg. Med. Chem. 2010, 18, 6874e6885; (c) Odlo, K.; Hentzen, J.; dit Chabert, J.
F.; Ducki, S.; Gani, O. A. B. S. M.; Sylte, I.; Skrede, M.; Flørenes, V. A.; Hansen, T.
V. Bioorg. Med. Chem. 2008, 16, 4829e4838.
4.5.5. Phenyl-(2,4,6-triisopropylbenzenesulfonyl)-acetonitrile
(27g). White solid (thermolysis: 155 ꢀC, 38 mg, 40%; Rh cat:
140 ꢀC/15 min, 2.3 mg, 14%); 1H NMR (500 MHz)
d 7.49e7.43 (m,
~
3. Meza-Avina, M. E.; Patel, M. K.; Lee, C. B.; Dietz, T. J.; Croatt, M. P. Org. Lett. 2011,
5H), 7.22 (s, 2H), 5.14 (s, 1H), 3.92 (sept, J¼6.9 Hz, 2H), 2.93 (sept,
J¼6.9 Hz, 1H), 1.28 (d, J¼6.9 Hz, 6H), 1.27 (d, J¼6.9 Hz, 6H), 1.20 (d,
J¼6.9 Hz, 6H). 13C NMR (125 MHz) 156.7, 153.0, 141.0, 130.7, 130.4
(2C), 129.4 (2C), 125.4, 124.8 (2C), 113.6, 100.1, 63.8, 34.5, 30.6 (4C),
25.4, 25.2, 23.7 (2C). IR 3138, 2956, 2928, 2868, 1597, 1457, 1430,
13, 2984e2987.
4. (a) Hyatt, I. F. D.; Croatt, M. P. Angew. Chem., Int. Ed. 2012, 51, 7511e7514; (b)
Hyatt, I. F. D.; Meza-Avina, M. E.; Croatt, M. P. Synlett 2012, 2869e2874.
5. (a) Boyer, J. H.; Mack, C. H.; Goebel, N.; Morgan, L. R. J. Org. Chem. 1958, 23,
1051e1053; (b) Robson, E.; Tedder, J. M.; Webster, B. J. Chem. Soc. 1963,
1863e1865; (c) Helwig, R.; Hanack, M. Chem. Ber. 1985, 118, 1008e1021; (d)
~
€
Huisgen, R.; Knorr, R.; Mobius, L.; Szeimies, G. Chem. Ber. 1965, 98, 4014e4021.
1386, 1361, 1193, 1159, 973, 950, 774, 694, 666, 579, 553 cmꢁ1
.
6. (a) Yoo, E. J.; Ahlquist, M.; Kim, S. H.; Bae, I.; Fokin, V. V.; Sharpless, K. B.; Chang,
S. Angew. Chem., Int. Ed. 2007, 46, 1730e1733; (b) Wang, F.; Fu, H.; Jiang, Y.;
Zhao, Y. Adv. Synth. Catal. 2008, 350, 1830e1834.
7. Harmon, R. E.; Stanley, F.; Gupta, S. K.; Johnson, J. J. Org. Chem. 1970, 35,
3444e3448.
8. (a) Horneff, T.; Chuprakov, S.; Chernyak, N.; Gevorgyan, V.; Fokin, V. V. J. Am.
Chem. Soc. 2008, 130, 14972e14974; (b) Chuprakov, S.; Kwok, S. W.; Zhang, L.;
Lercher, L.; Fokin, V. V. J. Am. Chem. Soc. 2009, 131, 18034e18035; (c) Chuprakov,
S.; Malik, J. A.; Zibinsky, M.; Fokin, V. V. J. Am. Chem. Soc. 2011, 133,
10352e10355; (d) Chattopadhyay, B.; Gevorgyan, V. Org. Lett. 2011, 13,
3746e3749; (e) Zibinsky, M.; Fokin, V. V. Angew. Chem., Int. Ed. 2013, 52,
1507e1510; (f) Gulevich, A. V.; Gevorgyan, V. Angew. Chem., Int. Ed. 2013, 52,
1371e1373; (g) Selander, N.; Worrell, B. T.; Fokin, V. V. Angew. Chem., Int. Ed.
2012, 51, 13054e13057; (h) Miura, T.; Funakoshi, Y.; Morimoto, M.; Biyajima, T.;
Murakami, M. J. Am. Chem. Soc. 2012, 134, 17440e17443; (i) Selander, N.;
HRMS [MþH]þ C23H30NO2S calculated: 384.19918; found:
384.19930.
4.5.6. Phenyl-(4-bromobenzenesulfonyl)-acetonitrile (27h). Yellow
solid (thermolysis: 156 ꢀC, 42 mg, 44%; Rh cat: 140 ꢀC/5 min, 30 mg,
33%); 1H NMR (500 MHz)
d
7.67 (d, J¼8.6 Hz, 2H), 7.55 (d, J¼8.6 Hz,
2H), 7.50e7.46 (m, 1H), 7.42e7.38 (m, 2H), 7.29 (d, J¼7.5 Hz, 2H),
5.15 (s, 1H). 13C NMR (125 MHz) 133.2, 132.8 (2C), 131.7 (2C), 131.4,
130.9, 129.9 (2C), 129.4 (2C), 125.2, 113.4, 63.3. IR 3086, 3065, 2921,
2852, 1572, 1455, 1389, 1333, 1162, 1147, 1080, 1067, 1009, 824, 783,
741, 694, 645, 587, 559 cmꢁ1. HRMS [MꢁH]ꢁ C14H9NO2S79Br
~
Please cite this article in press as: Meza-Avina, M. E.; et al., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.05.048

~
M.E. Meza-Avina et al. / Tetrahedron xxx (2013) 1e7
7
Worrell, B. T.; Chuprakov, S.; Velaparthi, S.; Fokin, V. V. J. Am. Chem. Soc. 2012,
134, 14670e14673.
9. (a) Gilchrist, T. L.; Gymer, G. E.; Rees, C. W. J. Chem. Soc. D, Chem. Commun. 1971,
1519e1520; (b) Gilchrist, T. L.; Gymer, G. E.; Rees, C. W. J. Chem. Soc., Perkin
Trans. 1 1973, 555e561.
10. Bae, I.; Han, H.; Chang, S. J. Am. Chem. Soc. 2005, 127, 2038e2039.
11. (a) Zhao, H.; Biehl, E. R. Synth. Commun. 1995, 25, 4063e4069; (b) Cid, M. B.;
ꢁ
Lopez-Cantarero, J.; Duce, S.; Ruano, J. L. G. J. Org. Chem. 2008, 74, 431e434.
12. Pirrung, M. C. In The Synthetic Organic Chemist’s Companion; John Wiley & Sons:
Hoboken, NJ, 2007; pp 171e172.
~
Please cite this article in press as: Meza-Avina, M. E.; et al., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.05.048