Palladium-Catalyzed Synthesis of 2-Aryl-2H-Benzotriazoles from Azoarenes and TMSN3

Article abstract of DOI:10.1021/acs.joc.5b01706

Substrate-directed ortho C-H amination of azoarenes using TMSN₃ as the source of nitrogen leading to the synthesis of 2-aryl-2H-benzotriazoles has been accomplished with the help of Pd/TBHP combinations. An intermolecular o-azidation (C-N bond formation) followed by an intramolecular N-N bond formation via nucleophilic attack of one of the azo nitrogen onto the o-azide nitrogen leads to cyclization with the expulsion of N₂.

Full text of DOI:10.1021/acs.joc.5b01706

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Article
Palladium-Catalyzed Synthesis of 2-Aryl-2H-
Benzotriazoles from Azoarenes and TMSN3
Nilufa Khatun, Anju Modi, Wajid Ali, and Bhisma K. Patel
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b01706 • Publication Date (Web): 15 Sep 2015
Downloaded from http://pubs.acs.org on September 20, 2015
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PalladiumꢀCatalyzed Synthesis of 2ꢀArylꢀ2HꢀBenzotriazoles
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from Azoarenes and TMSN3
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Nilufa Khatun, Anju Modi, Wajid Ali and Bhisma K. Patel*
Department of Chemistry, Indian Institute of Technology Guwahati, North Guwahati 781 039
Fax: (+91)361ꢀ26909762.
Eꢀmail: patel@iitg.ernet.in
RECEIVED DATE (will be automatically inserted after manuscript is accepted)
ABSTRACT: Substrate directed ortho C−H amination of azoarenes using TMSN3 as the source
of nitrogen leading to the synthesis of 2ꢀarylꢀ2Hꢀbenzotriazoles has been accomplished with the
help of Pd/TBHP combinations. An intermolecular oꢀazidation (C−N bond formation) followed
by an intramolecular N−N bond formation via nucleophilic attack of one of the azo nitrogen onto
the oꢀazide nitrogen leads to cyclization with the expulsion of N2.
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INTRODUCTION
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Direct C−H bond functionalization by transition metal catalysts has opened a plethora of
methods in the construction of C−C, C−N and C−hetero atom bonds.1ꢀ4 Strategies involving inert
C−H bond activation are important and significant due to their step and atom economy which
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circumvent preꢀfuctionalization of starting materials. In particular, directed C−H bond amination
strategies have received a great attention recently.5ꢀ7 A range of preactivated aminating reagents
such as Nꢀcarboxylates,8a Nꢀfluorobenzenesulfonimide (NFSI),8b Nꢀtosylates,8c Nꢀhalides,8d
benzoyl hydroxylamines,8e and highly active nitrene precursors, especially azides derivatives8fꢀ8h
have been explored as the potential aminating reagents under different metal catalysis.
Organic azides are important building blocks in synthetic chemistry and have found wide
applications in medicinal chemistry, material science, polymer and biological science.9
Generally, azide moiety is introduced into organic molecules via Sandmeyer reaction,10a,b Cuꢀ
catalyzed coupling of aryl halides/boronic acids with azides (NaN3 or TMSN3),10c,d coupling
between organometallics and TfN3,10e and metal free10fꢀh or metal mediated C−H
functionalization.10i,j As a nitrene precursor, ortho azido group can participate in intramolecular
cyclization after releasing a molecule of N2. Taking advantage of this, a number of metal
catalyzed protocols have been developed for the synthesis of nitrogen containing heterocycles.
Prefunctionalized 2ꢀazido substrates or the in situ generated ortho azido moiety introduced via
cross coupling reactions or C−H functionalization often undergo intramolecular cyclizations
leading to various heterocycles.11
2ꢀArylꢀ2Hꢀbenzotriazoles, are important nitrogen containing heterocycles which are found
extensively in pharmaceuticals and are structural components of many UV stabilizers and
organic electronic materials.12 Compounds having 2ꢀarylꢀ2Hꢀbenzotriazole scaffold as primary
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skeleton include a seratonine/dopamine receptor ligand (I), human PPARꢀα activator (II),
TinuvinꢀP (III) an ultraviolet light absorber, PCDTPBt (IV) an electron acceptor in organic solar
cell, an ultraviolet light stabilizer (V) and antiviral agent (VI) against ssRNA positive viruses are
shown in Figure 1.
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Figure 1. Important Compounds having 2ꢀArylꢀ2Hꢀbenzotriazole Cores
Existence of two isomeric benzotriazoles based on N1 (N3) and N2 substitutions* make the
selective synthetic strategies challenging. Because of the thermodynamic stability of N1 or 1H
isomer, compared to its N2 or 2H isomer more synthetic methods have been reported for the
former.13 Traditional methods for the regioselective and direct synthesis of 2ꢀarylꢀ2Hꢀ
benzotriazoles i.e N2ꢀisomer include: thermal decomposition of 2ꢀazidoazoarenes14a (Scheme 1,
path a), reduction of 2ꢀ[2ꢀnitrophenylazo] derivatives by thiourea14b and Zn/NH4Cl14c or
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nucleophilic aromatic (SNAr) substitution reaction with sodium azide14d (Scheme 1, path b),
oxidative coupling of ortho substituted azoaniline (Scheme 1, path c) by metal catalysts such as
SmI2,14e Zn14f or Cu.14g oꢀFunctionalized azoarenes are precursors in all the above strategies
which often are not easily accessible. Metalꢀcatalyzed arylation of unsubstituted benzotriazoles
are associated with the formation of a regioꢀisomeric mixture of N1ꢀ and N2ꢀbenzotriazoles
(Scheme 1, path d).14h,i Further, a copper catalyzed cross coupling of 2ꢀhaloaryltriazenes and
NaN3 leading to 2Hꢀbenzotriazoles has also been documented (Scheme 1, path e).14j A Rhꢀ
catalyzed ortho C−H activation of azobenzenes utilizing tosyl azide (TsN3) as the aminating
source provides 2Hꢀbenzotriazoles as depicted in Scheme 1, path f.14k
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Scheme 1. Reported Strategies for the Synthesis of 2ꢀArylꢀ2Hꢀbenzotriazole
Aromatic azoarenes constitute an important class of conjugated molecules due to which
they exhibit a diverse array of spectral properties. They find applications as industrial dyes, food
additives, photochemical molecular switches, hostꢀguest recognition, liquid crystal assemblies,
biomedical image analysis, molecular motor design, materials and protein probes.15 From
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synthetic point of view, in 1971 azoarenes as the directing group were first introduced by Fahey
for the oꢀhalogenation via a C−H activation strategy.16 However, its synthetic utility was
dormant, until very recently a series of transition metals catalyzed reactions involving azoarenes
as the directing substrates has been exploited. Examples include Pdꢀcatalyzed orthoꢀaroylation,17
oꢀnitration,14c,18a oꢀalkoxylation,18b and oꢀhalogenation18c Rhꢀcatalyzed alkyne annulations,18d
allylation,18e oꢀacylation and its transformation to indazoles18f and oꢀamination.18g,h In addition
Re and Rh catalyzed syntheses of nitrogenous heterocycles using aldehyde,19a αꢀdiazo esters19b
and diazotized Meldrum’s acid19c have been reported. With azo as the directing group, depending
upon the azides (as the source of nitrogen) either a six member or a five member heterocycle is
formed using Rh catalyst. The use of aryl azide (ArN3) provided phenazines as the sole product
[Scheme 2(a)],20 while tosyl azide gave exclusively 2Hꢀbenzotriazoles [Scheme (2b)].14k
Inorganic azide such as NaN3 with 2ꢀphenylpyridines as the directing group under a Pdꢀcatalyzed
condition gave fused heterocycle pyrido[1,2−b]indazoles as shown in [Scheme 2(c)].11d Although
an elegant transformation of azoarenes to 2Hꢀbenzotriazoles has been described by Lee group,
the use of expensive combinations of catalyst [Cp*RhCl2]2, coꢀcatalyst AgNTf2 and oxidant
PhI(OAc)2 make this method economically unviable.14k Thus, the development of an efficient,
cost effective and atomꢀeconomic protocol is very much in need. With our continuing efforts to
establish newer strategies for the synthesis of heterocycles through C−H activation,21 and taking
cues from the reports in Scheme 2 our investigation started. The main objective was to check
whether other commercially available metal catalyst and cheaper oxidant could be replacement
for the synthesis of 2Hꢀbenzotriazoles following oꢀC−H activation of azobenzene.
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Scheme 2. Metal Catalyzed ortho Amination of Directed Substrates with Different Azides
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RESULTS AND DISCUSSION
With this curiosity in mind and taking cues from the previous report11d as shown in (Scheme
2c), an initial trial experiment was performed by treating azobenzene (1a) (0.5 mmol) with NaN3
(1.0 mmol), in the presence of Pd(OAc)2 (10 mol%) and oxidant Ce(SO4)2 (1.0 mmol) in DMSO
o
at 100 C. No product formation was observed even after 72 h, only starting material (1a) was
recovered at the end of the reaction. The use of TMSN3 in lieu of NaN3 also failed to produce
any positive result. Disappointingly, other common oxidants used mostly in metal catalyzed C−H
functionalizations such as CAN, DDQ, Cu(OAc)2, Ag2O, K2S2O8, Oxone® and O2, were
completely unproductive (Table 1, entry 3). Interestingly, keeping all other parameters constant
the use of TBHP as oxidant (1 equiv) provided 2ꢀphenylꢀ2Hꢀbenzotriazole (2a) in 42% yield
(Table 1, entry 4). Encouraged by this preliminary success a series of reactions were performed
by varying other reaction parameters to obtain the best possible yield of (2a). At first, the
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catalytic efficacy of various Pdꢀcatalysts [Pd(OAc)2 (39%), PdCl2 (28%), PdBr2 (33%),
Pd(CH3CN)2Cl2 (21%)] were tested among which Pd(TFA)2 (49%) was found to be better as
shown in Table 1, entries 4−8. Although Pd(TFA)2 gave superior yield, on couple of
occasions the reaction flask exploded even at room temperature which prompted us to
avoid its use and we therefore switched to the next best catalyst Pd(OAc)2. The possible
explosion may be due to in situ generation of highly explosive HN3. The azide radical obtained
by the reaction of TMSN3 and TBHP is rapidly converted to HN3 by the in situ generated
trifluoroacetic acid from Pd(TFA)2 possibly causing the explosion. When the catalyst Pd(OAc)2
loading was increased to two fold i.e 20 mol%, the yield of the expected product improved up to
62% (Table 1, entry 9). No further significant improvement in the yield (65%) was observed
even when the catalyst loading was increased up to three fold (30 mol%). Other solvents such as
THF (<5%), dioxane (<5%), PhCl (41%) and DMF (48%) (Table 1, entries 11−14) tested under
otherwise identical conditions were all found to be inferior to DMSO. The oxidant TBHP (in
decane) was superior to other peroxide oxidants such as 70% aqueous TBHP (42%) and 30%
aqueous H2O2 (00%) (Table 1, entries 15−16) in terms of yield. A further improvement in the
product yield (70%) was observed when the oxidant (decaneꢀTBHP) amount was increased from
1 to 2 equiv (Table 1, entry 17). No further significant enhancement in the yield was observed
either by increasing the amount of aminating source i.e TMSN3 (3 equiv) (71%) or oxidant
TBHP (3 equiv) (73%) (Table 1, entries 18−19). Taking cues from previous reports,14k,11d effect
of additives such as O2, PhI(OAc)2, FeCl2 and Cu(OAc)2 were also examined along with decaneꢀ
TBHP as illustrated in Table 1, (entries 20−23). Unfortunately, none of the additives had any
positive effects on the product yield. Interestingly, when this reaction was carried out in an argon
atmosphere, the yield of the product improved up to (78%) as shown in Table 1, entry 24. By
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performing the reaction at lower temperature (80 C) led to a sluggish (36 h) reaction giving a
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lower yield (65%) of the product (Table 1, entry 25). It is not surprising that the reaction did not
proceed either in the absence of Pd(OAc)2 or TBHP suggesting the essential requirements of
both (Table 1, entries 26−27). Optimally, the desired product (2a) was obtained in a best possible
yield of 78% when the reaction was carried out using azobenzene (1a) (0.5 mmol), TMSN3 (2
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equiv), decaneꢀTBHP (2 equiv) in DMSO (1.0 mL) at 100 C under an atmosphere of argon. It
may be mention here that both catalyst Pd(OAc)2 and oxidant TBHP are not only commercially
available but are also cheaper compared to catalyst [Cp*RhCl2]2, coꢀcatalyst AgNTf2 and oxidant
PhI(OAc)2 combinations.
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Table 1. Screening of Reaction Conditionsa
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entry catalyst (mol%)
azide (equiv) oxidant (equiv)
solvent
additives
yield (2a) (%)b
1
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
PdCl2 (10)
NaN3 (2)
Ce(SO4)2 (1)
Ce(SO4)2 (1)
V.Oc,d (1)
TBHP (1)
TBHP (1)
TBHP (1)
TBHP (1)
TBHP (1)
TBHP (1)
TBHP (1)
TBHP (1)
TBHP (1)
TBHP (1)
TBHP (1)
Aq.TBHP (1)
Aq.H2O2 (1)
TBHP (2)
TBHP (2)
TBHP (3)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
THF
ꢀ
00
00
00
42
28
33
21
49
62
65
< 5
< 5
41
48
42
00
70
71
73
61
63
61
65
78f
2
TMSN3 (2)
TMSN3 (2)
TMSN3 (2)
TMSN3 (2)
TMSN3 (2)
ꢀ
3
ꢀ
4
ꢀ
5
ꢀ
6
PdBr2 (10)
ꢀ
7
Pd(CH3CN)2Cl2(10) TMSN3 (2)
ꢀ
8
Pd(TFA)2 (10)
Pd(OAc)2 (20)
Pd(OAc)2 (30)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
Pd(OAc)2 (20)
TMSN3 (2)
TMSN3 (2)
TMSN3 (2)
TMSN3 (2)
TMSN3 (2)
TMSN3 (2)
TMSN3 (2)
TMSN3 (2)
TMSN3 (2)
TMSN3 (2)
TMSN3 (3)
TMSN3 (2)
TMSN3 (2)
TMSN3 (2)
TMSN3 (2)
TMSN3 (2)
TMSN3 (2)
ꢀ
9
ꢀ
10
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20
21
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23
24
ꢀ
ꢀ
Dioxane
PhCl
ꢀ
ꢀ
DMF
ꢀ
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
O2
e
PhI(OAc)2
e
FeCl2
e
Cu(OAc)2
ꢀ
25
26
27
Pd(OAc)2 (20)
ꢀ
TMSN3 (2)
TMSN3 (2)
TMSN3 (2)
TBHP (2)
TBHP (2)
ꢀ
DMSO
DMSO
DMSO
ꢀ
ꢀ
65g
00
Pd(OAc)2 (20)
ꢀ
00
aReaction condition: azobenzene (0.5 mmol), in solvent (1.0 mL) at 100 oC for 24 h. Isolated yield. cV.O = CAN (1
b
d
equiv), DDQ (1 equiv), Cu(OAc)2 (1 equiv), Ag2O (1 equiv), K2S2O8 (1 equiv), Oxone (1 equiv) used under air. O2
balloon. e20 mol% under air. Reaction with argon balloon. gReaction was carried out for 36 h at 80 oC.
f
After establishing the optimized parameters, this protocol was subsequently applied to a
range of substituted azoarenes to afford their corresponding 2Hꢀbenzotriazoles. This protocol is
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found to be compatible with several functional groups such as electron donating alkyl [−Me
(1b−1f), −Et (1g and 1h), −iPr (1i) and −Bu (1j)], methoxy (−OMe) (1k), moderately electronꢀ
withdrawing halogens [−F(1l), −Cl (1m−1o) and −Br (1p)] and strongly electronꢀwithdrawing
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(−CF3) (1r) substituents in aromatic ring of azoarenes. All the substrates in Scheme 3 (1a−1r)
are symmetrically substituted azoarenes. Azoarenes possessing weakly activating substituents
such as pꢀMe (1b), mꢀMe (1c) and oꢀMe (1d) underwent oꢀaminativeꢀheterocyclization smoothly
giving their corresponding 2Hꢀbenzotriazoles (2b−2d) in moderate to good yields as shown in
Scheme 3. Symmetrically substituted diꢀmethylated azoarenes such as 3,4ꢀdimethyl (1e) and 2,4ꢀ
dimethyl (1f) under the optimized reaction conditions furnished their corresponding 2Hꢀ
benzotriazoles (2e) and (2f) respectively, in 87% and 65% yields (Scheme 3). Azoarenes
possessing other weakly activating substituents such as 4ꢀethyl (1g) and 2ꢀethyl (1h) reacted
under identical conditions to give (2g) and (2h) respectively, in 79% and 64% yields. Similarly,
the reaction of 4ꢀisopropyl (1i) and 4ꢀbutyl (1j) substituted symmetrical azoarenes under
standard conditions afforded 82% and 76% yields of their corresponding products (2i and 2j)
respectively. A moderate yield (72%) of (2k) was obtained when both the aryl rings are electron
rich due to the presence of methoxy (–OMe) (1k) substituent as in Scheme 3. However, the
azoarenes possessing weakly deactivating substituents, irrespective of their positions in the aryl
ring such as pꢀF (1l), pꢀCl (1m), mꢀCl (1n) and oꢀCl (1o), provided their respective 2Hꢀ
benzotriazoles (2l−2o) in moderate to poor yields (in the range of 63ꢀ35%). Other weakly
electronꢀwithdrawing substituents such as pꢀbromo (1p) under the standard conditions gave only
41% yield of (2p), while pꢀiodo (1q) failed to react which is mainly because of the electronic
effect of substituents and partly due to their insolubility in DMSO. Similarly, strongly electronꢀ
withdrawing substituents such as pꢀCF3 (1r) furnished only low yield (8%) of (2r) even after 50
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h which is mainly because of the electronic effect of –CF3 substituent. As can be seen in Scheme
3, barring one exception (1k) azoarenes bearing electronꢀdonating substituents (1b−1j) provided
better yields of their products (2b−2j) compared to those bearing electronꢀwithdrawing
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substituents (1l−1r). The higher yields obtained for electronꢀdonating azoarenes could be
attributed to their better chelating ability with electrophilic Pd (II) catalyst. The electronicꢀeffect
is dominated by the steric factor when the substituents are present at their ortho positions (1d, 1f,
1h and 1o) giving lower yields of products (2d, 2f, 2h and 2o) compared to their para and meta
analogues as shown in Scheme 3. All the meta substituted azoarenes (1c), (1e) and (1n) gave
single regioisomeric products (2c), (2e) and (2n) respectively. In these cases the less sterically
hindered oꢀC−H (i.e para to the meta substituents) is exclusively functionalized.
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Scheme 3. Substrate Scope for Symmetrical Azoarenesa,b
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aReaction condition: symmetrical azobenzene (0.5 mmol), TMSN3 (2 equiv), TBHPꢀdecane (2 equiv) in DMSO (1.0 mL) at 100
oC for 19ꢀ50 h. bIsolated yields of pure product.
After the successful synthesis of a series of 2Hꢀbenzotriazoles from symmetrical azoarenes
(Scheme 3) we then focused our attention on unsymmetrical azoarenes.** A query arises
whether this protocol will be applicable for the regioselective oꢀaminativeꢀheterocyclization or it
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would provide a mixture of –constitutional isomeric products? Keeping the substrate reactivity
trends from Scheme 3 in mind, some azoarenes were especially designed for this. These designed
azoarenes possess either electronꢀneutral (−H) or electronꢀdonating (−OMe) substituents in one
of the aromatic ring while the other ring contains electronꢀwithdrawing substituents such as oꢀ
COPh, oꢀNO2, pꢀCO2Me. Substrate (1as) bearing electronꢀwithdrawing oꢀCOPh group in one of
the aromatic ring and ꢀ electron neutral (−H) substituent in the other ring, when subjected to the
present reaction conditions, an inseparable constitutional isomeric mixture of 2Hꢀbenzotriazoles
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1
(2a′s) and (2as′) were obtained in the ratio of 4 : 3 (as judged from H NMR) in 64% yield
[Scheme 4(i)]. (E)ꢀ1ꢀ(2ꢀNitrophenyl)ꢀ2ꢀphenyldiazene (1at), another unsymmetrical azoarene,
under the present reaction conditions gave a product (2a) [(Scheme 4(ii)] having no intact nitro
group. This unexpected formation of product (2a) from unsymmetrical azoarene (1at) can be
explained by the intermolecular nucleophilic attack (SNAr) of the in situ generated oꢀazido
group on to the carbon attached to the nitro group. The product (2a) was obtained in a mere yield
of 14% and the rest being unreacted starting material. Nevertheless this reaction supports the
intermediacy of oꢀazido species. The failure to obtain a nitrophenylꢀsubstituted benzotriazole
from (1at) is possibly due to the presence of a strong deactivating ortho –NO2 substituent which
reduces the chelating ability of the ‘azo moiety’ towards electrophilic Pd (II). Another
unsymmetrical substrate (1au) containing pꢀCO2Me substituent in one aromatic ring and electron
neutral (−H) in the other ring, furnished a mixture of inseparable constitutional isomeric products
(2a′u) and (2au′) in the ratio of 2 : 1 in 57% yield (Scheme 4(iii)). Similarly, substrate (1ku)
having pꢀCO2Me group in one ring and pꢀOMe group in the other ring underwent oꢀaminativeꢀ
heterocyclization giving inseparable products (2k′u and 2ku′) in the ratio of 3.5 : 1. From the
above reactions [Scheme 4(i), (iii) and (iv)] it is evident that the oꢀaminativeꢀheterocyclization is
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preferred at the aromatic rings possessing electron donating substituent (ꢀOMe) followed by
electron neutral (−H), and the electronꢀwithdrawing substituents pꢀCO2Me and oꢀCOPh.
Scheme 4. Regioselectivity in unsymmetrical Azoarenesa,b
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Ph
O
N
N
N
H
Pd(OAc)2/TBHP
2a's
(
)
O
N
TMS
3
N N
(1as)
Ph
O
Ph
DMSO, 100 oC
Ar (balloon)
(i)
(ii)
(iii)
N
H
4 : 3
(64%, 31 h)
N
N
2as'
(
)
H
Pd(OAc)2/TBHP
N
TMSN3
N
N N
NO2
DMSO, 100 oC
Ar (balloon)
N
1at
2a
( )
(
)
H
(14%, 40 h)
N
N
H
N N
H
N
CO2Me
Pd(OAc)2/TBHP
TMSN3
2a'u
(
)
1au
(
)
DMSO, 100 oC
Ar (balloon)
2 : 1
N
N
N
CO2Me
CO2Me
CO2Me
(57%, 28 h)
(2au')
MeO
MeO
N
N
N
H
N N
H
Pd(OAc)2/TBHP
2k'u
(
)
TMSN3
(iv)
DMSO, 100 oC
Ar (balloon)
N
N
(1ku)
N
MeO
3.5 : 1
CO2Me
2ku'
(
)
(68%, 26 h)
CO2Me
aReaction condition: unsymmetrical azoarene (0.5 mmol), TMSN3 (2 equiv), TBHPꢀdecane (2 equiv) in DMSO (1 mL) at 100 oC
for 26ꢀ40h. bIsolated yields of product(s).
Some control reactions were performed to deduce the plausible reaction mechanism for this
transformation. When this reaction was carried out in the presence of a radical inhibitor TEMPO
(2,2,6,6ꢀtetramethylpiperidinooxy), no product formation (2a) was observed as shown in Scheme
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5(i). Thus complete suppression of the product formation of (2a) indicates a radical pathway for
this process. Formation of product (2a) from unsymmetrical azoarenes bearing oꢀnitro group
(1at) [Scheme 4(ii)] can be explained if there is formation of an oꢀazido species which is
possibly the intermediate in these reactions. When a preꢀsynthesized ortho azido azobenzene
(1aa) was treated under the present reaction conditions, formation of corresponding product 2ꢀ
phenylꢀ2Hꢀbenzotriazole (2a) was obtained in 86% yield as in Scheme 5(ii). This further
supports the intermediacy of ortho azido species for these reactions. The thermal decomposition
of (1aa) at 100 oC to (2a) in 83% yield suggests the non involvement of Pdꢀcatalyst and oxidant
(TBHP) in the final step [Scheme 5(iii)].
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Scheme 5. Control Reactions Performed
Based on these experimental results and taking cues from the recent literature precedent,17ꢀ
18,22ꢀ23
a plausible mechanism has been proposed as shown in Scheme 6. Presumably, an initial
cyclopalladation between ‘azo moiety’ of azobenzene and Pd(II) catalyst leads to the formation
of intermediate complex (A). The in situ generated azide radical,24 obtained by the reaction of
TMSN3 and TBHP, then reacts with Pdꢀcomplex (A), which is oxidized to give a Pd(III)23
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intermediate (B) (Scheme 6). A further oxidation of intermediate (B) by TBHP leads to the
formation of a Pd(IV)22 intermediate (C). Thus TBHP is playing the dual role of an oxidant as
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well as a radical generator. Apart from this, the BuO moiety generated from TBHP may act as
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one of the ligand for PdIV as in intermediate (C). A reductive elimination of intermediate (C)
leads to the formation of an ortho azido azobenzene (1aa) and regenerating palladium (II)
catalyst for the next cycle. In the final stage, attack of one of the azo nitrogen onto the oꢀazide
nitrogen of the in situ generated ortho azido substrate (1aa) leads to cyclization giving (2a),
with the expulsion of a molecule of N2.
Scheme 6. Plausible Mechanism for orthoꢀAminative Heterocyclyzation
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CONCLUSION
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In summary, we have developed an efficient and regioselective protocol for the synthesis
of 2ꢀarylꢀ2Hꢀbenzotriazoles via Pd(II)ꢀcatalyzed ortho sp2 C−H activation of azoarenes using
TMSN3 as the nitrogen source and TBHP as the oxidant. The ligand directed intermolecular
azidation (C−N bond formation) through ortho sp2 C−H functionalization of azobenzenes
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followed by intramolecular cyclization (N−N bond formation) leads to the construction of 2ꢀarylꢀ
2Hꢀbenzotriazoles. For unsymmetrical azoarenes the heterocyclization is preferred at the
aromatic ring rich in electron compared to electron neutral (−H) or electronꢀdeficient aromatic
rings. A wide range of substrates scope with tolerance of various functional groups make this
method a suitable alternative to the existing methods for the synthesis of 2ꢀarylꢀ2Hꢀ
benzotriazoles.
EXPERIMENTAL SECTION
General information:
All the compounds were commercial grade and were used without further purification.
Organic extracts were dried over anhydrous sodium sulfate. Solvents were removed in a rotary
evaporator under reduced pressure. Silica gel (60−120 mesh size) was used for the column
chromatography. Reactions were monitored by TLC on silica gel 60 F254 (0.25 mm). NMR
spectra were recorded in CDCl3 with tetramethylsilane as the internal standard for proton NMR
(600 MHz) and for 13C NMR (150 MHz). HRMS spectra were recorded using ESI mode (QꢀTOF
type Mass Analyzer). IR spectra were recorded in KBr or neat.
General Procedure for the Synthesis of 2ꢀPhenylꢀ2Hꢀbenzo[d][1,2,3]triazole (2a). Azobenzene
(1a, 91 mg, 0.5 mmol), Pd(OAc)2 (22 mg, 20 mol%), TMSN3 (115 mg, 1 mmol), TBHP in
decane (5ꢀ6 M) (200 µL, 1 mmol) and DMSO (1 mL) were sequentially added to a 25 mL oven
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dried roundꢀbottle flask containing a magnetic needle. Through a steady flow of argon gas the
flask was sealed with a rubber septum. To maintain a positive pressure of argon, the flask was
fitted with an argon balloon and the resultant reaction mixture was stirred in a preheated oil bath
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o
at 100 C. The progress of the reaction was monitored by TLC. After the completion of the
reaction as indicated by TLC, the reaction mixture was cooled to room temperature and diluted
with ethyl acetate (10 mL). Then the reaction mixture was filtered through a small bed of celite
and washed with an additional amount of ethyl acetate (20 mL). This combined organic layer of
ethyl acetate (30 mL) then washed with water (2 x 5 mL). The aqueous layer was separated using
a separating funnel and organic layer was dried over anhydrous Na2SO4 and the solvent was
removed under reduced pressure. The crude product was purified over a column of silica gel and
eluted with (95.5 : 0.5, hexane/ ethyl acetate) to give 2ꢀphenylꢀ2Hꢀbenzo[d][1,2,3]triazole (2a) in
78%.yield (76 mg) as yellowish solid.
2ꢀPhenylꢀ2Hꢀbenzo[d][1,2,3]triazole (2a). Yellowish solid; yield 76 mg, 78%; mp 98−100 C (Lit14k
o
mp 101−103 oC); 1H NMR (CDCl3, 600 MHz): δ (ppm) 7.42−7.44 (m, 2H), 7.45 (t, 1H, J = 7.8 Hz), 7.56
13
(t, 2H, J = 8.4 Hz), 7.93−7.95 (m, 2H), 8.36 (d, 2H, J = 7.8 Hz); C NMR (CDCl3, 150 MHz): δ (ppm)
118.5, 120.8, 127.3, 129.1, 129.6, 140.5, 145.2; IR (KBr): 3063, 2924, 2854, 1643, 1594, 1564, 1488,
1460, 1445, 1412, 1339, 1318, 1288, 1221, 1070, 1020, 963, 917, 809, 760 cmꢀ1; HRMS (ESI): calcd. for
C12H10N3 [M + H+] 196.0869; found 196.0871.
+
5ꢀMethylꢀ2ꢀ(pꢀtolyl)ꢀ2Hꢀbenzo[d][1,2,3]triazole (2b). Yellowish solid; yield 94 mg, 84%; mp
113−115 C (Lit14k 121−124 C); H NMR (CDCl3, 600 MHz): δ (ppm) 2.43 (s, 3H), 2.51 (s, 3H),
7.23−7.26 (m, 1H), 7.33 (d, 2H, J = 8.4 Hz), 7.66 (s, 1H), 7.80 (d, 1H, J = 9 Hz), 8.20 (d, 2H, J = 8.4 Hz);
13C NMR (CDCl3, 150 MHz): δ (ppm) 21.3, 22.4, 116.7, 117.8, 120.5, 130.1, 137.3, 138.4, 139.0, 143.8,
145.6; IR (KBr): 3059, 2922, 2852, 1627, 1562, 1508, 1449, 1351, 1311, 1275, 1220, 1175, 1166, 1115,
o
o
1
1104, 1040, 973, 841, 764 cmꢀ1; HRMS (ESI): calcd. for C14H14N3 (M + H+) 224.1182; found 224.1179.
+
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5ꢀMethylꢀ2ꢀ(mꢀtolyl)ꢀ2Hꢀbenzo[d][1,2,3]triazole (2c). Yellowish solid; yield 89 mg, 80%; mp 77−79
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7
8
oC (Lit14k 77−80 oC); 1H NMR (CDCl3, 400 MHz): δ (ppm) 2.48 (s, 3H), 2.51 (s, 3H), 7.24−7.26 (m, 2H),
7.42 (t, 1H, J = 8.0 Hz), 7.66 (s, 1H), 7.82 (d, 1H, J = 8.8 Hz), 8.12 (d, 1H, J = 8.4 Hz), 8.16 (s, 1H); 13C
NMR (CDCl3, 150 MHz): δ (ppm) 21.6, 22.4, 116.7, 117.8, 117.9, 121.2, 129.4, 129.7, 130.3, 137.5,
139.7, 140.6, 143.9, 145.7; IR (KBr): 3027, 2922, 2852, 1625, 1613, 1590, 1562, 1554, 1491, 1466, 1422,
1352, 1299, 1275, 1222, 1156, 1144, 1090, 1011, 972, 901, 879, 798, 780 cmꢀ1; HRMS (ESI): calcd. for
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+
C14H14N3 (M + H+) 224.1182; found 224.1185.
1
4ꢀMethylꢀ2ꢀ(oꢀtolyl)ꢀ2Hꢀbenzo[d][1,2,3]triazole (2d). Red liquid; yield 65 mg, 58%; H NMR
(CDCl3, 400 MHz): δ (ppm) 2.41 (s, 3H), 2.73 (s, 3H), 7.19 (d, 1H, J = 6.8 Hz), 7.33−7.43 (m, 4H), 7.69
(d, 1H, J = 7.2 Hz), 7.79 (d, 1H, J = 8.4 Hz); 13C NMR (CDCl3, 150 MHz): δ (ppm) 17.4, 18.9, 115.8,
126.0, 126.3, 126.8, 127.3, 129.3, 129.7, 131.8, 133.7, 140.6, 144.9, 145.5; IR (KBr): 3058, 2924, 2852,
1608, 1583, 1512, 1497, 1463, 1433, 1382, 1337, 1289, 1281, 1264, 1156, 1131, 1095, 1038, 969, 874,
+
792, 753, 711 cmꢀ1; HRMS (ESI): calcd. for C14H14N3 (M + H+) 224.1182; found 224.1187.
2ꢀ(3,4ꢀDimethylphenyl)ꢀ5,6ꢀdimethylꢀ2Hꢀbenzo[d][1,2,3]triazole (2e). Yellow solid; yield 109 mg,
o
1
87%; mp 193−195 C; H NMR (CDCl3, 600 MHz): δ (ppm) 2.33 (s, 3H), 2.38 (s, 3H), 2.41 (s, 6H),
13
7.26−7.28 (m, 1H), 7.64 (s, 2H), 8.01 (d, 1H, J = 5.4 Hz), 8.09 (s, 1H); C NMR (CDCl3, 150 MHz): δ
(ppm) 19.7, 20.1, 21.2, 116.8, 117.9, 121.5, 130.6, 137.5, 137.7, 138.1, 138.6, 144.5; IR (KBr): 3034,
2921, 2852, 1610, 1552, 1499, 1447, 1416, 1376, 1358, 1280, 1219, 1167, 1125, 1081, 1026, 1003, 971,
+
901, 880, 818, 720 cmꢀ1; HRMS (ESI): calcd. for C16H18N3 (M + H+) 252.1495; found 252.1497.
2ꢀ(2,4ꢀDimethylphenyl)ꢀ4,6ꢀdimethylꢀ2Hꢀbenzo[d][1,2,3]triazole (2f). Red Solid; yield 81 mg,
64%; mp 49−51 oC; 1H NMR (CDCl3, 600 MHz): δ (ppm) 2.35 (s, 3H), 2.41 (s, 3H), 2.48 (s, 3H), 2.68 (s,
3H), 7.02 (s, 1H), 7.15 (d, 1H, J = 7.8 Hz), 7.18 (s, 1H), 7.52 (s, 1H), 7.55 (d, 1H, J = 8.4 Hz); 13C NMR
(CDCl3, 150 MHz): δ (ppm) 17.3, 18.8, 21.3, 22.3, 113.9, 126.0, 127.4, 128.5, 128.9, 132.3, 133.2, 137.2,
138.3, 139.5, 144.1, 145.3; IR (KBr): 2947, 2921, 2854, 1697, 1623, 1579, 1510, 1498, 1447, 1380, 1335,
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+
5
6
(M + H+) 252.1495; found 252.1492.
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5ꢀEthylꢀ2ꢀ(4ꢀethylphenyl)ꢀ2Hꢀbenzo[d][1,2,3]triazole (2g). Red liquid; yield 99 mg, 79%; H NMR
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(CDCl3, 600 MHz): δ (ppm) 1.30 (t, 3H, J = 7.2 Hz), 1.33 (t, 3H, J = 7.8 Hz), 2.74 (q, 2H, J = 7.2 Hz),
2.81 (q, 2H, J = 7.8 Hz), 7.28 (dd, 1H, J1 = 1.2 Hz, J2 = 9.0 Hz), 7.36 (d, 2H, J = 8.4 Hz), 7.68 (s, 1H),
7.83 (d, 1H, J = 9.0 Hz), 8.23 (d, 2H, J = 8.4 Hz); 13C NMR (CDCl3, 150 MHz): δ (ppm) 15.5, 15.6, 28.7,
29.6, 115.3, 118.0, 120.6, 128.9, 129.3, 138.6, 143.7, 144.0, 145.4, 145.7; IR (KBr): 2964, 2925, 2853,
1629, 1561, 1512, 1455, 1376, 1310, 1284, 1266, 1241, 1218, 1175, 1113, 1052, 975, 965, 863, 838 cmꢀ1;
+
HRMS (ESI): calcd. for C16H18N3 (M + H+) 252.1495; found 252.1498.
4ꢀEthylꢀ2ꢀ(2ꢀethylphenyl)ꢀ2Hꢀbenzo[d][1,2,3]triazole (2h). Pale Yellow liquid; yield 80 mg, 64%;
1H NMR (CDCl3, 400 MHz): δ (ppm) 1.11 (t, 3H, J = 7.6 Hz), 1.42 (t, 3H, J = 7.6 Hz), 2.71 (q, 2H, J =
7.2 Hz), 3.12 (q, 2H, J = 7.6 Hz), 7.20 (d, 1H, J = 7.2 Hz), 7.36 (t, 2H, J = 8.0 Hz), 7.41−7.47 (m, 2H),
7.63 (d, 1H, J = 8.4 Hz), 7.77 (d, 1H, J = 8.8 Hz); 13C NMR (CDCl3, 150 MHz): δ (ppm) 14.3, 15.1, 25.2,
115.9, 124.1, 126.6, 126.8, 127.3, 130.0, 130.3, 135.4, 139.8, 140.2, 144.8, 145.1; IR (KBr): 3056, 2968,
2933, 2874, 1607, 1583, 1494, 1457, 1372, 1345, 1286, 1264, 1221, 1157, 1134, 1054, 971, 948, 872,
+
805, 754 cmꢀ1; HRMS (ESI): calcd. for C16H18N3 (M + H+) 252.1495; found 252.1491.
5ꢀIsopropylꢀ2ꢀ(4ꢀ isopropylphenyl)ꢀ2Hꢀbenzo[d][1,2,3]triazole (2i). Light red Solid; yield 114 mg,
81%; mp 58−60 oC; 1H NMR (CDCl3, 600 MHz): δ (ppm) 1.30 (s, 3H), 1.31 (s, 3H), 1.34 (s, 3H), 1.35 (s,
3H), 2.96−3.02 (m, 1H), 3.03ꢀ3.09 (m, 1H), 7.33(d, 1H, J = 8.4 Hz), 7.40 (d, 2H, J = 8.4 Hz), 7.73 (s,
1H), 7.85 (d, 1H, J = 9.0 Hz), 8.25 (d, 2H, J = 8.4 Hz); 13C NMR (CDCl3, 150 MHz): δ (ppm) 23.9, 24.1,
34.0, 34.7, 113.8, 118.1, 120.6, 127.5, 128.1, 138.6, 144.1, 145.6, 148.3, 149.9; IR (KBr): 2956, 2925,
2866, 1562, 1513, 1463, 1453, 1430, 1383, 1362, 1354, 1307, 1276, 1253, 1216, 1146, 1106, 1052, 1032,
+
969, 947, 864, 840, 818, 731 cmꢀ1; HRMS (ESI): calcd. for C18H22N3 (M + H+) 280.1808; found
280.1812.
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5ꢀButylꢀ2ꢀ(4ꢀ butylphenyl)ꢀ2Hꢀbenzo[d][1,2,3]triazole (2j). Reddish liquid; yield 117 mg, 76%; H
5
6
NMR (CDCl3, 400 MHz): δ (ppm) 0.93−0.97 (m, 6H), 1.32ꢀ1.44 (m, 4H), 1.61−1.72 (m, 4H), 2.69 (t, 2H,
7
8
9
J = 8.0 Hz), 2.76 (t, 2H, J = 8.0 Hz), 7.25−7.27 (m, 1H), 7.34 (d, 2H, J = 8.4 Hz), 7.66 (s, 1H), 7.82 (d,
1H, J = 8.8 Hz), 8.21 (d, 2H, J = 8.4 Hz); 13C NMR (CDCl3, 100 MHz): δ (ppm) 14.14, 14.16, 22.49,
22.52, 33.4, 33.7, 35.5, 36.3, 116.1, 117.9, 120.5, 129.5, 129.6, 138.6, 142.3, 144.0, 144.1, 145.6; IR
(KBr): 2955, 2932, 2857, 1629, 1608, 1561, 1512, 1465, 1427, 1378, 1352, 1277, 1257, 1234, 1141,
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1114, 1081, 1017, 970, 953, 930, 836, 808 cmꢀ1; HRMS (ESI): calcd. for C20H26N3 (M + H+) 308.2121;
+
found 308.2125.
5ꢀMethoxyꢀ2ꢀ(4ꢀ methoxyphenyl)ꢀ2Hꢀbenzo[d][1,2,3]triazole (2k). Yellowish solid; yield 92 mg,
o
o
1
72%; mp 140−142 C (Lit14k 147−150 C); H NMR (CDCl3, 400 MHz): δ (ppm) 3.89 (s, 3H), 3.91 (s,
3H), 7.04 (d, 2H, J = 9.6 Hz), 7.09 (dd, 1H, J1 = 2.4 Hz, J2 = 9.2 Hz), 7.12−7.13 (m, 1H), 7.78 (d, 1H, J =
13
9.2 Hz), 8.21 (d, 2H, J = 9.2 Hz); C NMR (CDCl3, 150 MHz): δ (ppm) 55.7, 55.8, 94.9, 114.7, 119.1,
121.7, 122.1, 134.3, 141.2, 146.0, 159.3, 159.9; IR (KBr): 3002, 2972, 2924, 2840, 1630, 1610, 1566,
1453, 1439, 1405, 1359, 1289, 1256, 1225, 1207, 1190, 1169, 1133, 1108, 1087, 1025, 970, 852, 837, 827
+
cmꢀ1; HRMS (ESI): calcd. for C14H14N3O2 (M + H+) 256.1081; found 256.1080.
5ꢀFluoroꢀ2ꢀ(4ꢀ fluorophenyl)ꢀ2Hꢀbenzo[d][1,2,3]triazole (2l). Brownish solid; yield 73 mg, 63%;
mp 169−171 oC; 1H NMR (CDCl3, 600 MHz): δ (ppm) 7.26−7.29 (m, 3H), 7.55 (d, 1H, J1 = 2.4 Hz, J2 =
13
9.0 Hz), 7.94−7.96 (m, 1H), 8.34−8.36 (m, 2H); C NMR (CDCl3, 150 MHz): δ (ppm) 116.6 (d, J = 24
Hz), 119.1 (d, J = 28.5 Hz), 120.3 (d, J = 10.5 Hz), 122.6 (d, J = 9 Hz), 136.7, 142.5, 145.2 (d, J = 15
Hz), 161.1, 162.7, 163.1 (d, J = 249 Hz); 19F NMR (CDCl3, 564.7 MHz): δ −111.9, −112.4; IR (KBr):
2958, 2923, 2853, 1663, 1614, 1603, 1568, 1509, 1429, 1409, 1353, 1303, 1279, 1222, 1158, 1121, 1096,
+
1085, 972, 956, 832, 803 cmꢀ1; HRMS (ESI): calcd. for C12H8F2N3 (M + H+) 232.0681; found 232.0682.
5ꢀChloroꢀ2ꢀ(4ꢀ chlorophenyl)ꢀ2Hꢀbenzo[d][1,2,3]triazole (2m). White solid; yield 75 mg, 57%;
mp 177−179 oC (Lit14k 185−187 oC); 1H NMR (CDCl3, 600 MHz): δ (ppm) 7.38 (dd, 1H, J1 = 1.8 Hz, J2 =
9.0 Hz), 7.53 (d, 2H, J = 9.0 Hz), 7.86 (d, 1H, J = 9.0 Hz), 7.91 (s, 1H), 8.28 (d, 2H, J = 9.0 Hz); 13C
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NMR (CDCl3, 150 MHz): δ (ppm) 117.6, 119.8, 122.0, 129.3, 129.9, 133.5, 135.4, 138.8, 143.9, 145.6;
5
6
IR (KBr): 3062, 2922, 2851, 1617, 1589, 1557, 1491, 1482, 1415, 1397, 1319, 1304, 1267, 1244, 1218,
7
8
35
+
1171, 1139, 1112, 1092, 965, 938, 861, 828, 754 cmꢀ1; HRMS (ESI): calcd. for C12H8 Cl2N3 (M + H+)
9
10
11
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13
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59
60
264.0090; found 264.0092.
5ꢀChloroꢀ2ꢀ(3ꢀ chlorophenyl)ꢀ2Hꢀbenzo[d][1,2,3]triazole (2n). White solid; yield 68 mg, 52%;
o
1
mp 157−159 C; H NMR (CDCl3, 600 MHz): δ (ppm) 7.38 (dd, 1H, J1 = 1.2 Hz, J2 = 9.0 Hz), 7.45 (d,
1H, J = 7.8 Hz), 7.49 (t, 1H, J = 7.8 Hz), 7.87 (d, 1H, J = 9.0 Hz), 7.92 (s, 1H), 8.24 (d, 1H, J = 7.8 Hz),
8.38 (s, 1H); 13C NMR (CDCl3, 150 MHz): δ (ppm) 117.6, 118.8, 119.9, 121.1, 129.4, 129.5, 130.8,
133.6, 135.6, 141.1, 143.8, 145.6; IR (KBr): 2955, 2923, 2852, 1594, 1586, 1556, 1483, 1453, 1437,
1280, 1266, 1243, 1218, 1109, 1071, 1049, 962, 938, 880, 862, 783, 762 cmꢀ1; HRMS (ESI): calcd. for
35
+
C12H8 Cl2N3 (M + H+) 264.0090; found 264.0092.
4ꢀChloroꢀ2ꢀ(2ꢀ chlorophenyl)ꢀ2Hꢀbenzo[d][1,2,3]triazole (2o). Colourless Gummy; yield 46 mg,
35%; 1H NMR (CDCl3, 600 MHz): δ (ppm) 7.41 (t, 1H, J = 7.8 Hz), 7.47−7.54 (m, 3H), 7.64 (d, 1H, J =
8.4 Hz), 7.75 (d, 1H, J = 6.6 Hz), 7.91 (d, 1H, J = 8.4 Hz); 13C NMR (CDCl3, 150 MHz): δ (ppm) 117.5,
118.8, 123.7, 126.9, 127.7, 127.8, 128.6, 131.2, 131.4, 138.7, 143.6, 145.8; IR (KBr): 2958, 2924, 2852,
1735, 1582, 1555, 1485, 1448, 1346, 1293, 1261, 1203, 1144, 1113, 1050, 1032, 979, 962, 870, 793, 704
cmꢀ1; HRMS (ESI): calcd. for C12H8 Cl2N3 (M + H+) 264.0090; found 264.0095.
35
+
5ꢀBromoꢀ2ꢀ(4ꢀ bromophenyl)ꢀ2Hꢀbenzo[d][1,2,3]triazole (2p). Brown Solid; yield 72 mg, 41%;
o
1
mp 160−162 C; H NMR (CDCl3, 600 MHz): δ (ppm) 7.50 (dd, 1H, J1 = 1.2 Hz, J2 = 9.0 Hz), 7.68 (d,
13
2H, J = 8.4 Hz), 7.80 (d, 1H, J = 9.0 Hz), 8.10 (s, 1H), 8.22 (d, 2H, J = 9.0 Hz); C NMR (CDCl3, 150
MHz): δ (ppm) 119.9, 120.9, 121.4, 122.2, 123.4, 131.6, 132.8, 139.2, 143.9, 146.1; IR (KBr): 2953,
2852, 1614, 1554, 1487, 1477, 1411, 1348, 1318, 1302, 1264, 1240, 1215, 1141, 1095, 1070, 1032, 1008,
964, 927, 824, 800 cmꢀ1; HRMS (ESI): calcd. for C12H8 Br2N3 (M + H+) 351.9079; found 351.9083.
79
+
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5ꢀ(Trifluoromethyl)ꢀ2ꢀ(4ꢀ(trifluoromethyl)phenyl)ꢀ2Hꢀbenzo[d][1,2,3]triazole (2r). Gummy;
yield 13 mg, 8%; 1H NMR (CDCl3, 600 MHz): δ (ppm) 7.63 (d, 1H, J = 8.4 Hz), 7.86 (d, 2H, J = 9.0 Hz),
7
8
9
13
8.07 (d, 1H, J = 9.0 Hz), 8.30 (s, 1H), 8.53 (d, 2H, J = 8.4 Hz); C NMR (CDCl3, 150 MHz): δ (ppm)
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117.6 (t, J = 4.5 Hz), 120.2, 121.3, 123.3, 124.0, 125.9, 127.1 (t, J = 4.5 Hz), 130.1 (q, J = 33 Hz), 131.8
(q, J = 33 Hz), 142.5, 144.3, 146.2; 19F NMR (CDCl3, 564.7 MHz): δ −63.5, −63.3; IR (KBr): 2956, 2924,
2853, 1639, 1614, 1569, 1510, 1471, 1429, 1360, 1321, 1265, 1244, 1168, 1134, 1107, 1065, 1045, 967,
945, 886, 847 cmꢀ1; HRMS (ESI): calcd. for C14H8N3F6 (M + H+) 332.0617; found 332.0620.
+
Phenyl (2ꢀphenylꢀ2Hꢀbenzo[d][1,2,3]triazolꢀ4ꢀyl)methanone + (2ꢀ(2Hꢀbenzo[d][1,2,3]triazolꢀ2ꢀ
1
yl)phenyl)(phenyl)methanone (2a′s + 2as′). Yellowish solid; yield 96 mg, 64%; H NMR (CDCl3,
600 MHz): δ (ppm) 7.18 (t, 2H, J = 7.8 Hz), 7.26−7.27 (m, 3H), 7.37 (t, 1H, J = 3.6 Hz), 7.43−7.52 (m,
5H), 7.61−7.67 (m, 6H), 7.69−7.72 (m, 2H), 7.75 (d, 1H, J = 7.2 Hz), 7.92 (d, 2H, J = 7.8 Hz), 8.16 (d,
1H, J = 8.4 Hz), 8.20 (d, 1H, J = 7.8 Hz), 8.32 (d, 2H, J = 7.8 Hz); 13C NMR (CDCl3, 150 MHz): δ (ppm)
118.4, 121.0, 122.7, 123.0, 123.6, 126.4, 127.3, 128.2, 128.4, 128.7, 128.9, 129.47, 129.55, 130.0, 130.2,
130.5, 131.3, 132.8, 133.1, 134.2, 137.2, 137.9, 138.5, 140.2, 143.2, 145.2, 145.8, 194.3, 195.2; IR (KBr):
3038, 2923, 2852, 1668, 1654, 1596, 1578, 1566, 1489, 1462, 1448, 1440, 1428, 1347, 1331, 1321, 1308,
1288, 1233, 1218, 1181, 1156, 1061, 998, 962, 937, 849, 773 cmꢀ1; HRMS (ESI): calcd. for C19H14N3O+
(M + H+) 300.1131; found 300.1130.
Methyl
2ꢀphenylꢀ2Hꢀbenzo[d][1,2,3]triazoleꢀ5ꢀcarboxylate
+
Methyl
4ꢀ(2Hꢀ
1
benzo[d][1,2,3]triazolꢀ2ꢀyl)benzoate (2a′u + 2au′). Light red solid; yield 72 mg, 57%; H NMR
(CDCl3, 600 MHz): δ (ppm) 3.95 (s, 3H), 3.99 (s, 3H), 7.44 (dd, 2H, J1 = 3.0 Hz, J2 = 6.6 Hz), 7.48ꢀ7.50
(m, 1H), 7.57 (t, 2H, J = 7.8 Hz), 7.93 (dd, 2H, J1 = 3.0 Hz, J2 = 6.6 Hz), 7.96 (d, 1H, J = 9.0 Hz), 8.06
(d, 1H, J = 9.0 Hz), 8.23 (d, 2H, J = 8.4 Hz), 8.37 (d, 2H, J = 7.8 Hz), 8.44 (d, 2H, J = 8.4 Hz), 8.72 (s,
1H); 13C NMR (CDCl3, 150 MHz): δ (ppm) 52.6, 52.7, 118.5, 118.7, 120.5, 121.0, 122.3, 122.8, 123.3,
127.3, 127.9, 129.2, 129.7, 129.8, 130.5, 130.8, 131.2, 140.3, 143.5, 144.6, 145.5, 146.9, 166.4, 166.9; IR
(KBr):, 2949, 2916, 2842, 1718, 1605, 1560, 1504, 1441, 1422, 1345, 1381, 1279, 1219, 1194, 1150,
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1136, 1011, 962, 855, 831, 807, 767, 747 cmꢀ1; HRMS (ESI): calcd. for C14H12N3O2 (M + H+) 254.0924;
found 254.0923.
+
6
7
8
Methyl 2ꢀ(4ꢀmethoxyphenyl)ꢀ2Hꢀbenzo[d][1,2,3]triazoleꢀ5ꢀcarboxylate + Methyl 4ꢀ(5ꢀmethoxyꢀ
9
1
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2Hꢀbenzo[d][1,2,3]triazolꢀ2ꢀyl)benzoate (2k′u + 2ku′). Yellowish solid; yield 96 mg, 68%; H
NMR (CDCl3, 600 MHz): δ (ppm) 3.89 (s, 3H), 3.91 (s, 3H), 3.96 (s, 3H), 3.98 (s, 3H), 7.06 (d, 2H, J =
9.0 Hz), 7.09−7.12 (m, 2H), 7.78 (d, 1H, J = 9.6 Hz), 8.01−8.04 (m, 2H), 8.20 (d, 2H, J = 9.0 Hz), 8.29
13
(d, 2H, J = 9.0 Hz), 8.37 (d, 2H, J = 9.0 Hz), 8.69 (s, 1H); C NMR (CDCl3, 150 MHz): δ (ppm) 52.5,
55.8, 94.7, 114.5, 114.7, 118.2, 119.4, 119.9, 122.0, 122.4, 122.5, 123.6, 125.4, 127.0, 129.9, 130.8,
131.2, 141.9, 143.5, 146.6, 159.9, 160.8, 166.4, 166.9; IR (KBr):, 2954, 2924, 2852, 1715, 1630, 1606,
1563, 1509, 1455, 1439, 1299, 1282, 1251, 1228, 1184, 1171, 1143, 1129, 1108, 1082, 1022, 967, 950,
+
855, 828, 802, 766 cmꢀ1; HRMS (ESI): calcd. for C15H14N3O3 (M + H+) 284.1030; found 284.1030.
AUTHOR INFORMATION
Corresponding Author
*E mail: patel@iitg.ernet.in.
ACKNOWLEDGMENT
B. K. P acknowledges the support of this research by the Department of Science and
Technology (DST) (SB/S1/OCꢀ53/2013), New Delhi, and the Council of Scientific and Industrial
Research (CSIR) (02(0096)/12/EMRꢀII). NK, AM and WA thank CSIR for fellowship.
Supporting Information
Spectral data (1H, 13C and 19F) for synthesized compounds. This Supporting Information is
available free of charge via the Internet at http://pubs.acs.org
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*
Benzotriazole notation: Benzotriazole is a fused heterocyclic compound having three
vicinal nitrogen atoms in its five member ring. This ring can exist in two tautomeric
forms viz. N1 (N3) or 1H isomer and N2 or 2Hꢀisomer due to the presence of one labile
proton as shown below:
The N1 and N3 isomers are identical due to their structural similarity. The N1 (1H) isomer
is predominantly present in equilibrium with N2 (2H) isomer at room temperature. The
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