Regioselective N1- or N2-modification of benzotriazoles with iodonium salts in the presence of copper compounds

Article abstract of DOI:10.1016/j.mencom.2018.05.019

Modification of benzotriazoles with iodonium salts [diphenyl- and (E)-styrylphenyliodonium tosylates] occurs at the N¹-position in the presence of K₂CO₃ as a base and CuI as a catalyst in CH₂Cl₂, wher

Full text of DOI:10.1016/j.mencom.2018.05.019

Mendeleev
Communications
Mendeleev Commun., 2018, 28, 287–289
Regioselective N1- or N2-modification of benzotriazoles
with iodonium salts in the presence of copper compounds
Dmitry V. Davydov,* Vladimir V. Chernyshev, Victor B. Rybakov,
Yurii F. Oprunenko and Irina P. Beletskaya
Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russian Federation.
Fax: +7 495 939 1854; e-mail: ddv@elorg.chem.msu.ru
DOI: 10.1016/j.mencom.2018.05.019
Modification of benzotriazoles with iodonium salts [diphenyl-
and (E)-styrylphenyliodonium tosylates] occurs at the N1-
position in the presence of K2CO3 as a base and CuI as a
catalyst in CH2Cl2, whereas in the presence of stoichiometric
amount of [Cu2(TMEDA)2(OH)2]Cl2 complex regioselective
N2-modification proceeds. Two new Cui complexes based on
benzotriazoles were synthesized and their crystal structures
were determined by X-ray powder diffraction analysis.
R1
R1
N
[R2IPh]+[TsO]–
[R2IPh]+[TsO]–
CuI, K2CO3
N
[Cu2(TMEDA)2(OH)2]Cl2,
CuI
N
H
R1
R1
R1
R1
R1 = H, Me
N
N
N
2 = Ph, CH=CHPh
N
R2
N
R
N
R2
59–67%
65–77%
N1-Modified benzotriazoles (BTAs) are of interest for their broad
synthetic use1 and high biological and pharmacological activity.2
In contrary, 2-N-substituted benzotriazoles are known as UV-
protectors and organic electronic materials.3 Classical methods for
the synthesis of N-modified BTAs are typically multistage. The
key stage for N1-arylated BTAs synthesis includes the cyclization of
o-amino-N-arylanilines in the course of diazotation.4 Alternatively,
they are accessed by chemoselective addition of organoazides to
benzynes.5 Syntheses of N2-arylated BTAs are based on decom-
position of C,N-diaryl tetrazoles,3(a),6 2-(o-azidophenyl)diazenyl-
arenes7(a),(b) or on reductive cyclization of 2-(o-nitrophenyl)-
diazenylarenes with thiourea,7(c) SmI2,7(d) Zn,7(e),(f) and via Piii/Pv=O
catalyst recycling in the presence of PhSiMe3.7(g)
Traditional methods of cyclization leading to N-arylated BTAs
can be implemented using transition metal catalysis. For example,
N1-arylated BTAs can be obtained by catalytic cyclization of
various ortho-halogenated 1,3-diaryltriazenes or from resin-linked
o-(arylamino)benzotriazenes in the presence of copper8 or
palladium catalysts,9(c),(d) or by Pd-catalyzed CH-activation of
diaryltriazenes.10 N2-Arylated BTAs can be synthesized by
copper(ii)-catalyzed oxidative cyclization of o-aminodiphenyl-
diazenes11(a) or o-halodiphenyldiazenes with azide group in the
presence of CuI.11(b) Modern approaches to N2-arylated BTAs are
based on CH-activation of diaryldiazenes and relative compounds
catalyzed by palladium(ii)3(a) and rhodium(iii).12 However, the
complexity of multistage processes are the main disadvantage of
the reported cyclization reactions.
under harsh reaction conditions is reported. Other source17 shows
formation of practically single N1-isomers,17 but also under drastic
conditions. The same trend is observed in the vinylation of BTAs.
Two N-vinylation protocols are described: the one with formation
of mixture of by-products and N-vinyl isomers18(a) and the other
with regioselective N1-vinylation.18(b)
Earlier we have investigated the regioselective arylation of
ambident azoles of high NH-acidity with iodonium salts.19 In the
present work, we propose two protocols for both regioselective
N1- and N2-modifications of benzotriazoles with iodonium salts
(see ref. 20) under mild conditions in the presence of copper
compounds. In the course of careful optimization with broad
variation of arylation agents, bases, additives and solvents, we
have found that regioselective N1-arylation and vinylation of
benzotriazoles with diphenyl- or (E)-styryl(phenyl)iodonium
salts (Scheme 1) readily occurs in CH2Cl2 with K2CO3 as the
base in the presence of CuI as catalyst at room temperature
(Table 1, entries 1–4).† On the contrary, in the presence of 0.5 mol
of [Cu2(TMEDA)2(OH)2]Cl2 (for the structure, see ref. 21)
serving as both the base and complexing additive, with the
iodonium salts and CuI being introduced within 15 min after
the additive, mostly the N2-modification took place (see Table 1,
entries 5–8).‡ However, if the iodonium salt and CuI were added
after one hour following the additive, predominantly N1-isomers
were formed though in very low yields. The same results were
obtained when pure complexes 4a or 4b isolated from reaction
†
The direct arylation of BTAs with iodonium salts occurring
either as nucleophilic substitution13(a),(b) or via the aryne mechanism
is practically unselective.13(c) N1-Vinylated BTAs can be obtained
by condensation of the corresponding N-derivatives of BTAs
possessing active methylene groups with carbonyl compounds
General procedure for the synthesis of N1-modified benzotriazoles
2a–d. Copper(i) iodide (0.05 mmol) in CH2Cl2 (30 ml) was added to a
mixture of substrate 1a or 1b (0.5 mmol), anhydrous K2CO3 (0.55 mmol)
and diphenyl- or (E)-styrylphenyliodonium tosylate (0.55 mmol) under argon
after 5–6 min of stirring. The resulting mixture was stirred under argon for
12 h at room temperature and then filtered. The filtrate was dried (MgSO4)
and purified by flash chromatography through basic alumina (eluent
CH2Cl2). The eluate was evaporated and the main product was isolated by
preparative chromatography on Merck silica gel plates (UV-254) using
ethyl acetate–n-hexane (1:6) as a solvent system. In the large scale (5 mmol)
experiments, the main products were isolated and purified by crystallization
from EtOH.
(c)
using Wittig,14(a) Peterson,14(b) or Horner–Wadsworth–Emmons14
reactions.
In view of N1 and N2 regioselectivitty and procedure convi-
nience, transition metal-catalyzed amination reaction of aryl-
(vinyl)halides with BTAs seems most challenging.15 The absence
of regioselectivity giving mixtures of N1- and N2-isomers16
© 2018 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
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Mendeleev Commun., 2018, 28, 287–289
R1
R1
N
N
N
C(8B)
i
C(7B)
C(9B)
C(4B)
R1
R1
R2
C(6B)
C(7A)
N
[R2IPh]+[TsO]–
C(8A)
C(9A)
2a–d
N
N(3B)
C(5B)
N(1B)
N
H
R1
R1
C(21)
C(22)
N
N
C(4A)
C(11a)
N(3A)
N(2)
ii
N
R2
C(12a)
N(1a)
1a R1 = H
C(6A)
C(5A)
N(1A)
N(2B)
1b R1 = Me
N(2A)
C(2)
3a–d
C(1a)
Cu(2a)
Cu(1)
Cl(1)
Cu(2)
Cl(1a)
C(1)
a R1 = H, R2 = Ph
C(2a)
b R1 = H, R2 = CH=CHPh
c R1 = Me, R2 = Ph
N(2Aa)
N(2a)
N(1)
N(2Ba)
C(5Aa)
N(1Ba)
N(1Aa)
C(11)
C(22a)
C(21a)
d R1 = Me, R2 = CH=CHPh
C(12)
N(3a)
C(6Aa)
C(4Aa)
C(7Aa)
C(5Ba)
N(3Ba)
C(4Ba)
Scheme 1 Reagents and conditions: i, K2CO3, 5% CuI, CH2Cl2, ~20°C,
12 h; ii, 50% [Cu2(TMEDA)2(OH)2]Cl2, 5% CuI, CH2Cl2, ~20°C, 12 h.
C(9Aa)
C(8Aa)
C(6Ba)
Table 1 N-modification of benzotriazoles 1a,b with iodonium salts
C(7Ba)
C(8Ba)
C(9Ba)
[R2IPh]+[TsO]–.a
R2 in
Products
N1 N2
Sub-
strate
Yieldb 2:3
Figure 2 Molecular structure of complex C36H48Cl2N16Cu3 4a.
Entry
iodonium Co-reagent
salt
(%) ratioc
1
2
3
4
5
6
7
8
1a
1a
1b
1b
1a
1a
1b
1b
Ph
PhCH=CH K2CO3
Ph K2CO3
PhCH=CH K2CO3
Ph
PhCH=CH [Cu2(TMEDA)2(OH)2]Cl2 2b 3b 62
Ph [Cu2(TMEDA)2(OH)2]Cl2 2c 3c 67
PhCH=CH [Cu2(TMEDA)2(OH)2]Cl2 2d 3d 61
K2CO3
2a 3a 65
2b 3b 77
2c 3c 69
2d 3d 58
15:1
18:1
20:1
19:1
1:16
1:18
1:20
1:19
C(81B)
C(7Aa)
C(81Aa)
C(71Aa)
C(8Aa)
C(9Aa)
C(4Aa)
C(71B)
C(7B)
C(8B)
C(9B)
C(4B)
[Cu2(TMEDA)2(OH)2]Cl2 2a 3a 59
C(12a)
C(21)
N(3Aa)
C(5Aa)
C(6B)
C(5B)
N(1Aa)
C(22)
N(2)
N(1a)
C(11a)
N(3B)
N(2B)
N(2Aa)
a Conditions: 5% CuI, CH2Cl2, ~20°C, 12 h, argon. b Isolated total yield
after column chromatography. c NMR data.
Cu(1)
N(1B)
C(1a)
C(2)
Cu(2)
C(1)
Cu(2a)
Cl(1a)
N(1A)
Cl(1)
C(2a)
N(2Ba)
N(1)
N(2a)
N(2A)
N(1Ba)
C(5Ba)
C(6Ba)
mixture were used as substrates in the absence of reagent and
catalyst.
C(11)
N(3Ba)
N(3A)
C(5A)
C(21a)
C(22a)
C(12)
We suppose that initially the [Cu2(TMEDA)2(OH)2]Cl2 additive
reacts with substrates 1 to form complexes with BTAs anions
i
C(4Ba)
C(4A)
C(6A)
C(9Ba)
C(7Ba)
C(71Ba)
C(7A)
nvolved as m-ligand bonded via N1- and N3-atoms. Such complexes
C(9A)
were earlier suggested to be involved in corrosion protection of
C(71A)
C(8A)
Cu-surface in the presence BTA22 (Figure 1). Due to such a manner
C(81Ba)
C(81A)
Figure 3 Molecular structure of complex C44H64Cl2N16Cu3 4b.
2+
Cu
N
N
N
N
N
N
of binding, N2-atom of BTA becomes available for reaction with
iodonium salts. Probably, these complexes are kinetically controlled
species that are further transformed to thermodynamically
controlled complexes such as 4a (Figure 2) and 4b (Figure 3)§,¶
Cu2+
Cu2+
N
N
Cu2+
N
N
N
Cu2+
N
N
N
N
n
§
Complexes 4a,b. [Cu2(TMEDA)2(OH)2]Cl2 powder (0.01 mmol) was
added to a solution of 1a or 1b·H2O (2 mmol) in CH2Cl2 (30 ml). After
10 min of stirring, the mixture was filtered and the filtrate was kept in a
refrigerator overnight. The blue microcrystals were collected, washed with
THF and CH2Cl2 and dried in vacuo.
Figure 1 The expected structures of kinetically controlled benzotriazole
complexes.
‡
General procedure for the synthesis of N2-modified benzotriazoles
¶
Crystal data for 4a: C36H48Cl2N16Cu3 (M = 966.45), monoclinic, space
3a–d. Copper(i) iodide (0.05 mmol) in CH2Cl2 (30 ml) was added to a
mixture of substrate 1a or 1b (0.5 mmol), [Cu2(TMEDA)2(OH)2]Cl2
(0.25 mmol) and diaryl- or (E)-styrylphenyliodoniun salt (0.55 mmol)
in CH2Cl2 (30 ml)after 15 min of stirring. The mixture was stirred for
12 h under argon atmosphere at room temperature, then treated with
10% aqueous NH3 and extracted several times with CH2Cl2. The extract
was dried (MgSO4) and purified by flash chromatography through basic
alumina (eluent CH2Cl2). The eluate was evaporated and the main product
isolated by preparative chromatography on Merck silica gel plates (UV-254)
using ethyl acetate–n-hexane (1:6) as a solvent system. In the experiment
of 1 mmol scale, the main product was isolated and purified by crystal-
lization from EtOH.
group P21/n, at 295 K: a = 15.7709(14), b = 12.2614(12) and c =
= 11.3651(11) Å, b = 108.627(17)°, V = 2082.6(4) Å3, Z = 2, dcalc
=
= 1.541 g cm–3, m(CuKa) = 3.354 mm–1, Rp/Rwp/Rexp = 0.0343/0.0446/
0.0149.
Crystal data for 4b: C44H64Cl2N16Cu3 (M = 1078.64), monoclinic,
space group P21/c at 295 K: a = 12.7381(12), b = 11.9853(11) and
c = 17.3467(15) Å, b = 108.223(17)°, V = 2515.5(4) Å3, Z = 2, dcalc
=
= 1.424 g cm–3, m(CuKa) = 2.835 mm–1, Rp/Rwp/Rexp = 0.0435/0.0602/
0.0399.
CCDC 1563239 and 1563250 contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk.
– 288 –

Mendeleev Commun., 2018, 28, 287–289
which are similar to the previously obtained,23 but proved to be
inert in reactions of this type.
In summary, a herein developed convenient method allows
one to perform direct regioselective modification of BTAs with
various iodonium salts at either N1 or N2 sites under mild con-
ditions. The regioselectivity is believed to result from differences
in coordination between copper complexes used.
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This work was supported by the Russian Ministry of Education
and Science (grant no. RFMEFI61616X0069). High resolution
mass spectra were recorded in the Department of Structural Studies
of N. D. Zelinsky Institute of Organic Chemistry RAS, Moscow.
Online Supplementary Materials
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Received: 21st November 2017; Com. 17/5413
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