The Disappearing Director: The Case of Directed N-Arylation via a Removable Hydroxyl Group

Article abstract of DOI:10.1002/adsc.201701611

A facile and broadly applicable method for the regiospecific N-arylation of benzotriazoles is reported. Copper-mediated reactions of diverse 1-hydroxy-1H-benzotriazoles with aryl boronic acids lead to 1-aryl-1H-benzotriazole 3-oxides. A N1-OH→N3 prototropy in the 1-hydroxy-1H-benzotriazoles is plausibly the underlying basis, where the tautomer is captured by the boronic acid, leading to C?N (not C?O) bond formation. Because the N?O bond in amine N-oxides and 1-hydroxy-1H-benzotriazoles can be easily reduced by diboron reagents such as (pinB)₂ and B₂(OH)₄, exposure of the 1-aryl-1H-benzotriazole 3-oxides to B₂(OH)₄ then leads to facile reduction of the N?O bond resulting in diverse, regiospecifically-arylated benzotriazoles. Thus, the N-hydroxyl group in 1-hydroxy-1H-benzotriazoles acts as a disposable arylation director. (Figure presented.).

Full text of DOI:10.1002/adsc.201701611

Title: The Disappearing Director: The Case of Directed <i>N</i>-
Arylation <i>via</i> a Removable Hydroxyl Group
Authors: Magdalena Andrezjewska, Prasanna Vuram, Narender
Pottabathini, Venkateshwarlu Gurram, Siva Relangi, Kirill
Korvinson, Raju Doddipalla, Lothar Stahl, Michelle Neary,
Padmanava Pradhan, Somesh Sharma, and Mahesh
Lakshman
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201701611
Link to VoR: http://dx.doi.org/10.1002/adsc.201701611

10.1002/adsc.201701611
Advanced Synthesis & Catalysis
The Disappearing Director: The Case of Directed N-Arylation via a Removable
Hydroxyl Group
Magdalena R. Andrzejewska,[a] Prasanna K. Vuram,[a] Narender Pottabathini,[b]
Venkateshwarlu Gurram,[b] Siva Subrahmanyam Relangi,[b] Kirill A. Korvinson,[a,c] Raju
Doddipalla,[b] Lothar Stahl,[d] Michelle C. Neary,[e] Padmanava Pradhan,[a] Somesh Sharma,[b]
and Mahesh K. Lakshman*[a,c]
[a] Department of Chemistry, The City College of New York, 160 Convent Avenue, New
York, New York 10031, USA
E-mail: mlakshman@ccny.cuny.edu
[b] Discovery Services, GVK Biosciences, Pvt. Ltd., 28A IDA Nacharam, Hyderabad 500076,
Telangana, India
[c] The Ph.D. Program in Chemistry, The Graduate Center of the City University of New
York, New York, New York 10016, USA
[d] Department of Chemistry, University of North Dakota, 151 Cornell Street Stop 9024,
Grand Forks, North Dakota 58202, USA
[e] Department of Chemistry, Hunter College, 695 Park Avenue, New York, New York
10065, USA
 Supporting information for this article is available on the WWW under…
Abstract
A facile and broadly applicable method for the regiospecific N-arylation of benzotriazoles is
reported. Copper-mediated reactions of diverse 1-hydroxy-1H-benzotriazoles with aryl
boronic acids lead to 1-aryl-1H-benzotriazole 3-oxides. A N1-OH  N3 prototropy in the 1-
hydroxy-1H-benzotriazoles is plausibly the underlying basis, where the tautomer is
captured by the boronic acid, leading to C–N (not C–O) bond formation. Because the N–O
bond in amine N-oxides and 1-hydroxy-1H-benzotriazoles can be easily reduced by diboron
reagents such as (pinB)2 and B2(OH)4, exposure of the 1-aryl-1H-benzotriazole 3-oxides to
B2(OH)4 then leads to facile reduction of the N–O bond resulting in diverse, regioselectively-
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10.1002/adsc.201701611
Advanced Synthesis & Catalysis
arylated benzotriazoles. Thus, the N-hydroxyl group in 1-hydroxy-1H-benzotriazoles acts
as a disposable arylation director.
Keywords: arylation, benzotriazoles, directing group, copper, boronic acid
Introduction
Among heterocycles, benzotriazoles are an important family of compounds with wide-
ranging uses. In medicinal chemistry, many have shown important biological activities.[1–4]
In relation to the present work, 1-aryl-1H-benzotriazoles display promise against various
diseases. Some examples containing N-aryl-linked benzotriazoles are shown in Figure 1.
Among these, the tetrahydronaphthalene derivative is a ligand for retinoid X receptors, and
showed significant activity against type-2 diabetes in vivo.[5] The pyrimidine-benzotriazole
conjugates were shown to be potent inhibitors of JNK1 (mitogen-activated protein kinase
1), with selectivity over JNK2.[6] The acridine derivatives showed antibacterial activity,
comparable to ampicillin, against S. areus, B. subtilis, and E. coli.[7] The benzotriazolyl
chalcones demonstrated antifilarial activity against Setaria cervi causing parasitic death,[8]
and against Plasmodium falciparum.[9]
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10.1002/adsc.201701611
Advanced Synthesis & Catalysis
Figure 1. N1-aryl benzotriazoles possessing biological activities.
Also, benzotriazoles are corrosion inhibitors for copper and copper alloys,[10] they are
found in formulations that contact metals (such as aircraft deicing and brake fluids, and in
metal-cutting fluids),[11] and are antifog agents in photographic applications.[12]
Benzotriazoles are important in organic synthesis,[13] including as ligands in cross-coupling
reactions.[14]
Many methods, metal-catalyzed and uncatalyzed, have been developed for the N-
arylation of benzotriazoles, but reaction at the N1 and N2 and formation of regioisomeric
products from unsymmetrical benzotriazoles have to be contended with. Among methods
not involving metal-mediated processes, the most common is diazotization of N-aryl-o-
phenylenediamines.[15]
Also, reaction of 2-(arylamino)iminophosphoranes with
NaNO2/AcOH results in N1-arylbenzotriazoles.[16] Perhaps the most convenient access is
via cycloaddition of arynes with aryl azides but this can yield regioisomers with
unsymmetrical arynes.[17] Among methods involving metals, Pd-mediated C–H bond
activation/C–N bond formation in 1,3-diphenyltriaz-1-enes[18] and 1,7-Pd migration-
cyclization-demethylation of 3-methyl-1,3-diphenyltriaz-1-enes have been reported.[19]
1H-Benzotriazole itself has been used as a substrate for Cu-mediated arylation. Examples
o
are: the Cu(OAc)2-catalyzed reaction of an aryllead derivative at 140 C (1 example, N1/N2
ratio = 3.8 : 1),[20] arylation with a CuI-diamine system at 110 oC (2 examples, N1/N2 ratio >
o
25 : 1),[21] and CuBr2/n-Bu4N+F– mediated arylation at 145 C (in 2 examples, N1/N2 ratios
= 1.3–2.7 : 1).[22] Cyclization of o-halo-1,3-diphenyltriaz-1-enes to N1-aryl benzotriazoles
has been accomplished via catalysis by CuI.[23–25] In a Cu(OAc)2-catalyzed method, 1H-
benzotriazole underwent reaction with substituted thiophenes, furans, and pyrroles, in the
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10.1002/adsc.201701611
Advanced Synthesis & Catalysis
presence of Selectfluor.[26] N-(2-Hydroxyaryl)benzotriazoles have been prepared by O-
arylation with diaryliodonium triflates, followed by a [3,3] sigmatropic rearrangement.[27]
A summary of these methods is shown in Scheme 1.
Scheme 1. Previous approaches to N1-aryl benzotriazoles.
Results and Discussion
In this report, we present a new approach to regiospecific N1 arylation of
benzotriazoles that is directed by a remote hydroxyl group. In previous work, we
demonstrated facile reduction of 1-hydroxy-1H-benzotriazoles (BtOH) by exposure to
B2(OH)4 and Et3N in MeCN (Scheme 2).[28] In that work we proposed that a possible
mechanism for the reduction could involve the N1-OH  N3 prototropy, which would
expose an N-oxide type of intermediate. Such a species could be reduced by a diboron
reagent. In this context, we and others have shown general approaches for the reduction of
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10.1002/adsc.201701611
Advanced Synthesis & Catalysis
N–O bonds in amine N-oxides and O6-(benzotriazolyl) purine nucleosides by diboron
reagents.[29–31] Tautomerism in BtOH is known to be solvent dependent. The N-hydroxy
form has been crystallized from water-free EtOH/Et2O after drying the compound over
o
P2O5 at 50 C, whereas the N-oxide form was obtained from MeOH/H2O.[32] Also, acylation
of BtOH can produce O- or N-acylation, depending upon the polarity of the reaction
medium,[33–35] and the O-acyl compound completely isomerizes to the N-acyl form in the
solid state.[35]
B2(OH)4, Et3N
N
MeCN, 50 oC
N
R
N
H
H
N
N
N
Plausible minor
tautomer
N
R
N
R
N
OH
O
Ar
Ar
B2(OH)4
N
MeCN, 50 oC
N
New method
N
N
R
R
Ar B(OH)2
N
N
O
Scheme 2. Reduction of BtOH derivatives and a proposed approach to hydroxyl-directed
N-arylation of benzotriazoles.
On the basis of the tautomerism exhibited by 1-hydroxy-1H-benzotriazoles[32–35] and
our prior results,[28] we reasoned that it should be possible to capture the N-oxide tautomer
in a Chan-Lam-Evans type of reaction.[36–38] The ensuing product would be an N1-aryl-1H-
benzotriazole 3-oxide, which could then be reduced to the corresponding 1H-benzotriazole,
removing the directing hydroxyl handle. We should note that reaction of BtOH and p-Me-
PhB(OH)2, using Cu(OAc)2 and either pyridine or Et3N, has previously been reported.[39]
The product obtained was identified as the O-arylated product, but our results herein
indicate a different outcome. While our work was being completed a similar method for
Cu-catalyzed N-vinylation of 1-hydroxy-1H-benzotriazoles, leading the N-oxides was
reported.[40] In that work, several reactions of BtOH with aryl boronic acids were also
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10.1002/adsc.201701611
Advanced Synthesis & Catalysis
recorded, but only two substituted 1-hydroxy-1H-benzotriazoles were studied.[40]
Comparisons of the methods are presented later.
Our present work commenced with evaluation of conditions for the reaction of 1-
hydroxy-1H-benzotriazole (BtOH) with PhB(OH)2, at room temperature (data in Table 1).
Between ClCH2CH2Cl and CH2Cl2, the latter proved to be superior, and no reaction occurred
in DMSO (entries 1–3). We reasoned that one possible cause for the promising but modest
result in CH2Cl2 could be the water solubility of what we considered was 1-phenyl-1H-
benzotriazole 3-oxide. This notion was supported by the improved 77% yield that was
obtained when the reaction mixture was directly chromatographed, without aqueous
workup (entry 4). Replacement of pyridine with either Et3N or 2,2’-bipyridine gave
inferior results. Lowering the amount of Cu(OAc)2 (entries 7 and 8) also proved to be
detrimental, clearly indicating the need for a stoichiometric amount (98% Cu(OAc)2 costs <
$1/mol).
Table 1. Optimization of conditions for reaction of BtOH with PhB(OH)2.[a]
Entry
Solvent
Conditions
Yield [%][b]
27[c]
1
2
3
4
5
6
7
8
9
10
ClCH2CH2Cl Cu(OAc)2 (1 equiv.), pyridine (4 equiv.)
CH2Cl2
DMSO
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Cu(OAc)2 (1 equiv.), pyridine (4 equiv.)
Cu(OAc)2 (1 equiv.), pyridine (4 equiv.)
Cu(OAc)2 (1 equiv.), pyridine (4 equiv.)
Cu(OAc)2 (1 equiv.), Et3N (4 equiv.)
Cu(OAc)2 (1 equiv.), 2,2’-bipyridine (2 equiv.)
Cu(OAc)2 (0.25 equiv.), pyridine (4 equiv.)
Cu(OAc)2 (0.5 equiv.), pyridine (4 equiv.)
CuI (1 equiv.), pyridine (4 equiv.)
42[c]
NR[d]
77[e]
30[e]
10[e]
14[e]
26[e]
11[e]
CuCl (1 equiv.), pyridine (4 equiv.)
14[e]
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10.1002/adsc.201701611
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[a] Reactions were conducted with 100 mg of BtOH in 2 mL of solvent, under a
balloon filled with O2 gas.
[b] Yield is of isolated and chromatographically purified product.
[c] Reaction mixture was subjected to an aqueous workup.
[d] NR = no reaction.
[e] Reaction mixture was directly chromatographed without aqueous workup.
Figure 2. X-ray crystallographic structure of 1-phenyl-1H-benzotriazole 3-oxide (1) and
crystal packing (thermal ellipsoids are shown at the 50% probability level).
Whereas evidence pointed to the product of this Cu-mediated transformation to be 1-
phenyl-1H-benzotriazole 3-oxide, confirmation was necessary. Therefore, the product was
crystallized and analyzed crystallographically (Figure 2).[41] This unequivocally indicated
that the product was the expected N-oxide and not the O-aryl product.
Having established both reaction conditions and the structure of the product from the
arylation step, we proceeded to evaluate the generality of the reaction. Several aryl
boronic acids were reacted with BtOH and these data are summarized in Figure 3. Some
comparisons to the previous report[40] are perhaps instructive. Our reactions were
typically conducted with 1.1 equiv. of the aryl boronic acid (except where indicated within
parenthesis in Figure 3) and 4 equiv. of pyridine, in CH2Cl2 at room temperature, in the
presence of molecular sieves. The reported reactions were conducted with 3 equiv. of the
o
aryl boronic acid and 10 equiv. of pyridine, in 1,4-dioxane at 40 C, in the presence of
Na2SO4.[40] The product yields with phenyl and 2-naphthylboronic acid under both sets of
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10.1002/adsc.201701611
Advanced Synthesis & Catalysis
conditions, were comparable (1: 77% in both cases, 10: 73% here versus 68% reported[40]).
Thus, excess aryl boronic acid may not always be necessary, however, we observed yields
to improve with excess aryl boronic acid in some cases where yields were low (9, 13, and
15). Notably, in both reports, a stoichiometric amount of Cu(OAc)2 was necessary.
Figure 3. Products and yields from the reactions of BtOH with 1.1 equiv. of aryl boronic
acids (yields in parentheses are from reactions with 2 equiv. of the boronic acid).
1-Hydroxy-1H-benzotriazoles are relatively straightforward to access[28,42] and so
reactions of substituted benzotriazoles with various aryl boronic acids were investigated.
Generally good yields were observed with 6-chloro BtOH and a superior yield was obtained
in a reaction with 2 equiv. of PhB(OH)2. 6-Bromo BtOH reacted very well with just 1.1
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10.1002/adsc.201701611
Advanced Synthesis & Catalysis
equiv. of the three boronic acids. With 6-phenyl BtOH high yields were attained with all
three boronic acids and, notably, excellent yields were obtained with p-nitrophenylboronic
acid and 3-thienylboronic acid. The latter gave a modest yield with BtOH.
Figure 4. Products and yields from the reactions of 6-substituted BtOH derivatives with
1.1 equiv. of aryl boronic acids (yield in parentheses is from reaction with 2 equiv. of the
boronic acid).
At this stage we decided to reduce all (26) 1-aryl-1H-benzotriazole 3-oxides. 1-
Hydroxy-1H-benzotriazoles were reduced by B2(OH)4 and Et3N, under generally mild
conditions.[28] In the present cases, because the products of the arylation reactions are
already N-oxides, they were reduced with only B2(OH)4. The reduction products are shown
in Scheme 3 and as can be seen from the reduction of 12 to 38, this reaction is also scalable.
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10.1002/adsc.201701611
Advanced Synthesis & Catalysis
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10.1002/adsc.201701611
Advanced Synthesis & Catalysis
Scheme 3. Reduction of the 1-aryl-1H-benzotriazole 3-oxides with B2(OH)4.
Although the X-ray structure of compound 1 had hinted at the regiochemical outcome
1
of these reactions, as a second step the H NMR data for 5-chloro-1-(p-tolyl)-1H-
benzotriazole (44) were compared to those reported for 6-chloro-1-(p-tolyl)-1H-
benzotriazole, and these are distinctly different.[43]
As definitive proof of the
regiospecificity of this chemistry, compound 44 was crystallized and a crystal structure
was obtained (Figure 5).[44] This conclusively demonstrated the location of the aryl group
relative to the halogen atom, substantiating our initial hypothesis that the N-hydroxyl
group directs the arylation step, and that it can be used as a removable handle for the
regiospecific N-arylation of benzotriazoles.
Figure 5. X-ray crystal structure of 5-chloro-1-(p-tolyl)-1H-benzotriazole (44) and crystal
packing (thermal ellipsoids are shown at the 50% probability level).
We also investigated reactions of 5,6-dichloro BtOH.[30] In this case, while performing
the arylation and reduction as separate reactions, we observed that 5,6-dichloro-1-aryl-1H-
benzotriazole 3-oxides were difficult to purify and were possibly prone to degradation.
Thus, we decided to evaluate the arylation and reduction as a two-step, one-pot process
(Table 2, entries 1–3). In three cases, after the N-arylation step (with 1.1 equiv. of each aryl
boronic acid), the solvent was evaporated and the reduction was performed with B2(OH)4
in MeCN. In the phenyl case (53), a significant improvement in yield was observed, while
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10.1002/adsc.201701611
Advanced Synthesis & Catalysis
modest yield improvements were observed with the 2-naphthyl (54) and p-bromophenyl
(55) cases. The three final products were obtained without any difficulty. On the basis of
the above observations three other two-step, one-pot reactions were conducted with 1.1
equiv. of the aryl boronic acids to assess if there was any advantage to be gained with the
latter. Compounds 34, 39 and 43 were selected (Table 2, entries 4–6) due to the somewhat
lower yields observed in the arylation step in these cases. The results indicate that no
major yield advantage was gained via the two-step, one-pot approach, and that this may be
beneficial when the intermediate N-oxide is prone to degradation.
Table 2. Synthesis of six N-aryl-1H-benzotriazoles via two-step and two-step, one-pot
processes.
Ar =
Entry
X and Y
Product Two step Two step,
one pot
1
2
3
X = Y = Cl
X = Y = Cl
X = Y = Cl
53
54
55
45%
34%
20%
62%
39%
26%
4
X = Y = H
34
54%
50%
5
6
X = Y = H
39
43
33%
48%
34%
42%
X = H, Y = Cl
As seen in Figure 1, azaheterocycles at the N1 position of a benzotriazole result in
compounds with biological activity. Therefore, we decided to introduce a pyrimidine motif
via the use of 2-methoxypyrimidine-4-boronic acid (Scheme 4). Cautioned by the lower
yields observed in the reactions of heteroaryl boronic acids, two reactions were conducted:
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10.1002/adsc.201701611
Advanced Synthesis & Catalysis
(a) one with 1.1 equiv. of the pyrimidine boronic acid, at room temperature over 24 h, and
(b) the second with 2 equiv. of the boronic acid, also at room temperature, but over 48 h,
due to the limited solubility of the boronic acid. As in reactions of BtOH with heteroaryl
boronic acids (Figure 3), yields were modest (22% and 31%) with the higher equivalence
giving the better yield. Nevertheless, this demonstrates that physiologically important
motifs can be introduced via this methodology.
Scheme 4. Synthesis of an N-aryl benzotriazole containing a biologically relevant
pyrimidine motif.
Because these reactions were conducted in a non-polar solvent, we anticipated the N1-
OH  N3 prototropy to be minor and thus, the hydroxyl form to be the major component
under the reaction conditions. It is known that substituents on the benzotriazole can
influence the extent of this tautomerism but, generally, the N-hydroxy form remains major
in EtOH, whereas the N-oxide predominates in water.[45] However, we were curious to
assess the energy differences between the N-hydroxy and N-oxide tautomers in a set of
representative examples, in vacuo, in CH2Cl2 (the reaction solvent), and in water. For this
we chose BtOH, 6-Cl-BtOH, 5,6-di-Cl-BtOH, 6-Ph-BtOH, and the corresponding N-oxides.
DFT computations were conducted using the B3LYP/6-311++(d,p) basis set and the results
are shown in Table 3 (see the Supporting Information for details).
Table 3. Free energy differences between the N-oxide and N-hydroxy forms (GN-oxide – GN-
hydroxy) in kcal/mol of 1-hydroxy-1H-benzotriazole and four of its derivatives.
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10.1002/adsc.201701611
Advanced Synthesis & Catalysis
X, Y
Gvacuo GCH Cl
GH2O
2
2
H, H
H, Cl
Cl, Cl 0.822
H, Ph 0.23
–0.10
1.11
–3.46
–2.64
–2.63
0.70
–4.32
–3.57
–3.51
0.21
These data indicate that even in CH2Cl2, a solvent of modest dielectric constant ( =
9.08), the N-oxide form is preferred for BtOH as well as its 6-Cl-BtOH and 5,6-di-Cl-BtOH,
and this preference increases in water ( = 78.54). However, these computations indicate a
slight preference for the N-oxide form of BtOH in vacuo, but in the remaining three cases
the N-hydroxy form is preferred. 6-Ph-BtOH is the exception, where under all conditions a
preference for the N-hydroxy form is seen. Thus, the notion that substituents influence the
tautomerism is supported by these computations but they also seem to indicate that the
tautomerism could be altered in either direction.
Ar B(OH)2
LnCuII(OAc)2
LnCuII(OAc)2
AcOB(OH)2
LnCuIOAc
+ AcOH + ½O2
Ar
LnCuII
LnCuIOAc
O
N
OAc
N
N
AcOH +
HO
Ar
LnCuII(OAc)2
LnCuI(OAc)
O
N
N
R
N
N
LnCuIIIAr(OAc)2
N
N
H
R
R
N-Hydroxy
N-Oxide
Scheme 5. A proposed catalytic cycle for the N-arylation of 1-hydroxy-1H-benzotriazoles.
On the basis of the mechanism proposed for the etherification of p-cresol with MeOH,[46]
we anticipate a pathway as shown in Scheme 5. This proceeds by formation of an aryl-CuII
species followed by oxidation to an aryl-CuIII by another CuII, reaction of the aryl-CuIII
species with BtOH, reductive-elimination from the CuIII intermediate, and a reoxidation of
the formed CuI to CuII.
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10.1002/adsc.201701611
Advanced Synthesis & Catalysis
In previous work,[40] species leading up to reductive elimination were evaluated by DFT
computations. An N-coordinated intermediate that would produce the N-oxide product
was slightly higher in energy (by 0.2 kcal/mol) than the corresponding O-coordinated
species that would lead to O-arylation. However, the transition state leading to N-arylation
was lower in energy (by 3 kcal/mol) as compared to that leading to O-arylation. Also, the
N-oxide product is lower in energy (by 5.9 kcal/mol) than the O-aryl isomer. We now offer
a computational perspective into the N-hydroxy/N-oxide tautomerism of BtOH, which is
also a part of this overall process.
Conclusions
Herein, we have demonstrated a facile approach to the regiospecific N-arylation of 1H-
benzotriazoles, which involves a Cu-mediated reaction with aryl boronic acids. We believe
that the N1-OH  N3 prototropy in 1-hydroxy-1H-benzotriazoles, even in non-polar
solvents, can be utilized to capture the N-oxide tautomer with aryl boronic acids. This
reaction can then drive the reaction forward. This hypothesis is consistent with the
formation of 1-aryl-1H-benzotriazole 3-oxides as intermediates. Facile reduction of these
N-oxides with B2(OH)2 then yields the N1-aryl benzotriazoles. Thus, the hydroxyl moiety
functions as an easily disposable arylation-directing group, rendering this a regiospecific N-
arylation. Both our results and those previously published[40] indicate that the reaction
requires stoichiometric Cu(OAc)2, but our reactions can be conducted at room temperature
with nearly stoichiometric amounts of aryl boronic acids in most cases. In some cases
where yields were lower, these could be improved by increasing the boronic acid
stoichiometry to 2 equiv. The present data and those published[40] indicate that contrary to
the anticipated formation of O-aryl ethers,[39] as from reactions of phenols with aryl
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10.1002/adsc.201701611
Advanced Synthesis & Catalysis
boronic acids,[36,37] N-arylation is the operative mechanism in the reactions of 1-hydroxy-
1H-benzotriazoles. As shown here, this can be exploited for the regiospecific N-arylation of
benzotriazoles.
Acknowledgements
Support of this work by NSF Grant CHE-1265687 to MKL as well as PSC CUNY awards to MKL
and PP is gratefully acknowledged. We thank AllyChem for a sample of B2(OH)4 used in this
work. Infrastructural support at CCNY was provided by NIH grant G12MD007603 from the
National Institute on Minority Health and Health Disparities. We thank Dr. Gopal
Subramaniam at Queens College for assistance in obtaining some NMR spectra.
Computational results were obtained via the City University of New York High Performance
Computing Center at the College of Staten Island that was supported, in part, by NSF awards
CNS-0958379, CNS-0855217, ACI-1126113.
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Advanced Synthesis & Catalysis
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[43] 500 MHz H NMR data for 5-chloro-1-(p-tolyl)-1H-benzotriazole (44) in CDCl3: 8.12
(s, 1H, ArH), 7.66–7.62 (m, 3H, ArH), 7.50 (d, J = 8.8 Hz, 1H, ArH), 7.42 (d, J = 7.2 Hz,
2H, ArH), 2.48 (s, 3H, Me). 300 1H NMR data for 6-chloro-1-(p-tolyl)-1H-benzotriazole
in CDCl3:[23] 8.05 (d, J = 8.6 Hz, 1H, ArH), 7.71 (d, J = 1.5 Hz, 1H, ArH), 7.61 (d, J = 8.3
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TOC Graphic
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