A novel straightforward synthesis of 2,4,6-triaryl-1,3,5-triazines via copper-catalyzed cyclization of N-benzylbenzamidines

Article abstract of DOI:10.1016/j.tetlet.2014.10.091

A novel, straightforward method for the synthesis of 2,4,6-triaryl-1,3,5-triazines via copper-catalyzed cyclization of N-benzylbenzamidines in DMSO has been developed. Compared to other methods, the present protocol has a number of advantages such as - cost-effectiveness, avoidance of aldehydes or alcohols as reaction partners, and easy accessibility of starting materials, making it a highly practical approach to access various 2,4,6-triaryl-1,3,5-triazines.

Full text of DOI:10.1016/j.tetlet.2014.10.091

Accepted Manuscript
A Novel Straightforward Synthesis of 2,4,6-Triaryl-1,3,5-triazines via Copper-
Catalyzed Cyclization of N-Benzylbenzamidines
Pradip Debnath, K.C. Majumdar
PII:
S0040-4039(14)01785-7
DOI:
http://dx.doi.org/10.1016/j.tetlet.2014.10.091
TETL 45320
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
9 September 2014
7 October 2014
9 October 2014
Please cite this article as: Debnath, P., Majumdar, K.C., A Novel Straightforward Synthesis of 2,4,6-Triaryl-1,3,5-
triazines via Copper-Catalyzed Cyclization of N-Benzylbenzamidines, Tetrahedron Letters (2014), doi: http://
dx.doi.org/10.1016/j.tetlet.2014.10.091
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Graphical Abstract
A Novel Straightforward Synthesis of 2,4,6-Triaryl-1,3,5-triazines via
Copper-Catalyzed Cyclization of N-Benzylbenzamidines
∗
Pradip Debnath and K. C. Majumdar
a
b
a
Department of Chemistry, Ramkrishna Mahavidyalaya, Kailashahar, Unakoti, Tripura-799277, INDIA.
Department of Chemistry, University of Kalyani, Kalyani, W.B.-741235, INDIA.
b
Ar1
1
Ar1
CuCl (5 mol%), O (1 atm)
2
N
N
Ar -CH NH
2
HN
2
Ar2 CN
Nitrile
ο
DMSO, 100 C
Ar2
Ar2
Ar2
N
NH
N-Benzylbenzamidine
68-84%
2,4,6-Triaryl-1,3,5-triazine
∗
Corresponding author. Tel.: +91-3824-222210, fax: +91-3824-222210; e-mail: pdn0099@yahoo.co.in
1

A Novel Straightforward Synthesis of 2,4,6-Triaryl-1,3,5-triazines via
Copper-Catalyzed Cyclization of N-Benzylbenzamidines
∗a
b
Pradip Debnath and K. C. Majumdar
a
Department of Chemistry, Ramkrishna Mahavidyalaya, Kailashahar, Unakoti, Tripura-799277, INDIA.
Department of Chemistry, University of Kalyani, Kalyani, W.B-741235, INDIA.
b
Abstract: A novel, straightforward method for the synthesis of 2,4,6-triaryl-1,3,5-triazines via
copper-catalyzed cyclization of N-benzylbenzamidines in DMSO has been developed. Compared
to other methods, the present protocol has a number of advantages such as- cost-effectiveness,
avoidance of aldehydes or alcohols as reaction partners and easy accessibility of starting materials,
making it a highly practical approach to access various 2,4,6-triaryl-1,3,5-triazines.
Keywards: Symmetrical and unsymmetrical triazines, benzamidines, copper-catalyst, DMSO.
Introduction:
Aryl-substituted 1,3,5-triazines are a remarkably important class of nitrogen containing
1
heterocycles in the pharmacological area because of their broad range of biological activities. In
addition, these compounds serve as chelating ligands for the preparation of organometallic
2
materials, liquid crystals, and transition-metal catalysts. Despite extensive functions, only a few
3
4
methods are reported for the preparation of this class of compounds. Conventionally, such a goal
5
can be realized by cyclotrimerization of nitriles catalyzed by acids, bases or Lewis acids. However,
these methods suffer either harsh reaction conditions such as high temperature, high pressure or low
product yields and limited substrate scope that is restricted to the synthesis of only symmetrical
2,4,6-trisubstituted-1,3,5-triazines. Moreover, the cyclotrimerization of nitriles generally needs
excess of amines as the co-catalyst which could increase the complexity of work-up procedure. Very
recently, Martinez-Alvarez et al. described a modified, one-pot synthetic protocol for the
∗
Corresponding author. Tel.: +91-3824-222210, fax: +91-3824-222210; e-mail: pdn0099@yahoo.co.in
2

preparation of 2,4,6-trisubstituted-1,3,5-triazine derivatives via controlled cross-cyclotrimerization
6
of nitriles using equimolecular amount of triflic anhydride. Alternative approaches to the synthesis
of 2,4,6-trisubstituted-1,3,5-triazine derivatives based on the Suzuki-coupling reactions between
7
halogenated 1,3,5-triazines and aryl boronic acids were developed. Main disadvantage of these
approaches is the use of less-environmentally benign halogenated substrates which could produce
stoichiometric amounts of undesirable waste and result in a detrimental influence on the
environment. Recently, the condensation of aromatic aldehydes with amidines has provided a direct
pathway for the synthesis of symmetrical as well as unsymmetrical aryl substituted 1,3,5-triazine
8
derivatives. However, the use of aldehydes as the coupling partners could frequently meet some
9
problems such as- (i) active aldehyde groups may suffer from an oxidation reaction leading to the
formation of undesirable by-products; (ii) aldehydes could undergo a decarbonylation reaction under
harsh reaction conditions resulting in lower yields of the products; (iii) cost of some aldehydes are
high or not readily available. The method, therefore, does not offer unrestricted scope for the
8
a
synthesis of products with wide variation. Recently, Zhang et al. have applied amidines and
primary alcohols as latent aldehydes for the synthesis of aryl substituted 1,3,5-triazines by using
2 2
costly [RuCl (p-Cymene)] as dehydrogenative catalyst. Although this protocol is effective under
relatively mild conditions, high cost of catalyst as well as the use of alcohols as reaction partners are
the main disadvantages of this protocol. Hence, search for easily available, inexpensive substrate as
well as catalyst would provide a new avenue for direct synthesis of 2,4,6-trisubstituted-1,3,5-
triazines and is of high importance.
Scheme 1
Recently, direct oxidation of amines to imines has attracted much attention. By employing
suitable catalyst systems, the dehydrogenation of the amines leading to in situ formation of
methanimine is recognized as the key point for the formation of desired imines. In this context,
10a
10b
Adimurthy et al.
and Kerton et al.
have independently developed copper-based catalytic
systems for the direct oxidation of primary and secondary benzylamines to imines. Taking cue from
3

the aforesaid elegant contributions, it is reasonable to expect that the copper-catalyst could also be
applied to the oxidation of benzylic position of N-benzylamidines to azadines A (Scheme 1) which
on dehydrogenative cyclization with another molecule of amidine would provide 1,3,5-triazines. To
our delight, it was found that copper catalysts function well in this context. The present protocol
offers a variety of advantages such as - cost-effectiveness, avoids aldehydes or alcohols as reaction
1
1
partner and easy accessibility of the starting materials. The aforesaid thought led us to undertake a
study to explore the synthesis of both symmetrical and unsymmetrical 2,4,6-triaryl-1,3,5-triazines
from N-benzylbenzamidines. To the best of our knowledge, such a synthetic protocol has not yet
been reported.
The possibility of a direct synthesis of 2,4,6-triaryl-1,3,5-triazine has been examined by using
commercially available Cu-salts as catalyst. N-Benzylbenzamidine (1a) was selected as a model
ο
substrate. The reactions were carried out at 100 C for 15 h using 5 mol % of Cu-salt in DMSO
I
solvent. As indicated in Table 1, among different copper sources examined, Cu salts were found
II
better than Cu salts and CuCl was found to be the best catalyst giving product 2a in 78 % yield
(
Table 1, entries 1-8). Screening of various solvents in the presence of CuCl as catalyst indicated
that polar solvents (DMF, HFIP) and less polar THF or non-polar toluene as solvents are less
effective than DMSO (Table 1, entries 9-12). Both decrease and increase of the reaction
temperatures resulted in the formation of products in lower yields (Table 1, entries 13 and 14).
Moreover, no reduction of reaction time was observed even when the catalyst loading was increased
to 10 mol% (Table 1, entry 15). By using the optimized catalyst and solvent, it was found that the
rate of reaction was sluggish in open air, and the reaction required 36 h to reach completion as
2
compared to 15 h in the presence of O (1 atm) (Table 1, entry 16). No reaction occurred without
1
copper catalyst (Table 1, entry 17). Hence, the optimized conditions are summarised as follows: 5
2
ο
(1 atm) and 100 C temperature (Table 1,
mol% of CuCl catalyst, DMSO as the reaction solvent, O
entry 2).
2
4

Table 1
With the optimized conditions in hand, the substrate scope of this copper-catalyzed synthetic
protocol was examined. First, the compatibility with substituents in the phenyl ring of the
benzamidines was investigated (Table 2, entries 2-6). The reaction has also smoothly proceeded
with the substrates bearing the substituents in the phenyl ring of N-benzyl moiety of the N-
benzylbenzamidines (Table 2, entries 7-10). Both the electron withdrawing (F, Cl, Br, CF
3
) (Table
2, entries 2-5) and electron donating (OMe, Me) (Table 2, entries 6-10) substituents are well
tolerated. It was observed that the amidines containing electron-donating groups (OMe, Me)
afforded the products in higher yields (Table 2, entries 6-10) than those containing the electron-
3
withdrawing ones (F, Cl, Br, CF ) (Table 2, entries 2-5). The phenomenon may be explained by
assuming that oxidative addition of copper to amidine nitrogen may occur more easily when a more
basic amidine (electron-donating) is used (Scheme 2). In the overall process two molecules of N-
benzylamidine are involved for the formation desired triazines with the release of one molecule of
2
1
N-benzyl amines. Thus the products are comprised of two units of Ar and only one Ar . It is also
noteworthy that halogen substituted N-benzylbenzamidines performed well, leading to halo-
substituted 2,4,6-triaryl-1,3,5-triazines which may be used for further transformation to liquid
7
d,13
crystalline materials.
heteroarylamidine (1k) using this protocol furnished heteroaryl substituted 1,3,5-dihydrotriazine
2k) instead of substituted 1,3,5-triazine.
An attempt to synthesize heteroaryltriazines, a representative reaction of
(
Table 2
On the basis of copper-catalyzed formation of imines from benzylamines as well as the
1
0
conventional 1,3,5-triazine synthesis, a plausible pathway for the formation of 2,4,6-triaryl-1,3,5-
triazines from N-benzylamidines is depicted in Scheme 2. The reaction is initiated by oxidative
action of copper catalyst at the benzylic position of N-benzylbenzamidine to form azadiene A. The
subsequent inter- and intra-molecular nucleophilic addition of the amino group to the electrophilic
carbon centre may generate the intermediate B and racemic aminals C. Then, thermodynamically
5

favourable deamination may release dihydrotriazine D and N-benzyl amine. Finally, the desired
product 2 is formed via dehydrogenative aromatization of D which is promoted either by copper
catalyst or oxygen (oxidation).
Scheme 2
In summary, a new efficient method for the synthesis of 2,4,6-triaryl-1,3,5-triazines from N-
benzylbenzamidines using easily available CuCl as catalyst has been developed. This is the first
report of using readily accessible N-benzylbenzamidines as a single component starting material for
the synthesis of 2,4,6-triaryl-1,3,5-triazines. The cyclization process proceeds efficiently and
furnishes the products in good to excellent yields. This protocol does not require aldehydes or
alcohols as reaction partners. Hence, compared to conventional synthetic methodologies, it is a
significantly improved protocol with advantages such as- operational simplicity, cost-effectiveness
and easy accessibility of the starting materials. On the basis of importance of 2,4,6-triaryl-1,3,5-
triazines in biological, material, and coordination chemistry, this protocol has the potential for
applications.
Acknowledgement: One of us (P.D) thanks University Grants Commission (New Delhi) for
research grant.
References and notes:
1. (a) Suda, A.; Kawasaki, K.; Komiyama, S.; Isshiki, Y.; Yoon, D.-O.; Kim, S. J.; Na, Y.-J.;
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Stewart, M.; Barrett, M. P.; Brun, R.; Gilbert, I. H. J. Med. Chem. 2001, 44, 3440. (g) Iino, Y.;
Karakida, T.; Sugamata, N.; Andoh, H.; Takei, H.; Takahashi, M.; Yaguchi, S.; Matsuno, T.;
Takehara, M.; Sakato, M.; Kawashima, S.; Morishita, Y. Anticancer Res. 1998, 18, 171.
6

2
. (a) Naik, S.; Kumaravel, M.; Mague, J. T.; Balakrishna, M. S. Inorg. Chem. 2014, 53, 1370. (b)
Xiao, C.-Y.; Li, Y.-M.; Lun, H.-J.; Cui, C.-Y.; Xu, Y.-Q. J. Solid State Chem. 2013, 208, 127.
. (a) Roy, B.; De, N.; Majumdar, K. C. Chem. Eur. J. 2012, 18, 14560. (b) Majumdar, K. C.; De,
3
N.; Roy, B.; Bhowmik, A. Liq. Cryst. 2010, 37, 1459. (c) Kotha, S.; Kashinath, D.; Kumar, S.
Tetrahedron Lett. 2008, 49, 5419. (d) Lee, C.-H.; Yamamoto, T. Bull. Chem. Soc. Jpn. 2002, 75,
6
1
4
4
5
15. (e) Goldmann, D.; Janietz, D.; Schmidt, C.; Wendroff, J. H. Angew. Chem. Int. Ed. 2000, 39,
851.
. (a) Hernandez-Juarez, M.; Vaquero, M.; Alvarez, E.; Salazar, V.; Suarez, A. Dalton Trans. 2013,
2, 351. (b) Santra, P. K.; Sagar, P. J. Mol. Catal. A: Chem. 2003, 197, 37.
. Examples on cyclotrimerization of nitriles, see: (a) Goetmann, F.; Fischer, A.; Antonietti, M.;
Arne, T. New J. Chem. 2007, 31, 1455. (b) Kuhn, P.; Antonietti, M.; Arne, T. Angew. Chem., Int.
Ed. 2008, 47, 3450. (c) Herrera, A.; Martinez-Alvarez, R. Ramiro, P.; Chioua, M.; Chioua, R.
Synthesis 2004, 503. (d) Diaz-Ortiz, A.; de la Hoz, A.; Moreno, A.; Sanchez-Migallon, A.; Valiente,
G. Green Chem. 2002, 4, 339. (e) de la Hoz, A.; Diaz-Ortiz, A.; Elguero, J.; Martinez, L. J.;
Moreno, A.; Sanchez-Migallon, A. Tetrahedron 2001, 57, 4397. (f) Lee, C.-H. ; Yamamoto, T.
Tetrahedron Lett. 2001, 42, 3993. (g) Xu, F.; Sun, J.-H.; Yan, H.-B.; Shen, Q. Synth. Commun.
2
000, 30, 1017. (h) Rieke, R. D.; Hansson, M. V. Tetrahedron 1997, 53, 1925. (i) Spencer, R. D.;
Beggs, B. H. Anal. Chem. 1963, 35, 1633.
. Herrera, A.; Riano, A.; Moreno, R.; Caso, B.; Pardo, Z. D.; Fernandez, I.; Saez, E.; Molero, D.;
Sanchez-Vazquez, A.; J. Org. Chem. 2014, 79, 7012.
. For recent examples via Suzuki coupling reactions, see: (a) Tanaka, H.; Shizu, K.; Miyazaki, H.;
6
7
Adachi, C. Chem. Commun. 2012, 48, 11392. (b) Liu, J.; Wang, K.; Xu, F.; Tang, Z.; Zheng, W.;
Zhang, J. Li, C.; Yu, T.; You, X. Tetrahedron Lett. 2011, 52, 6492. (c) Achelle, S.; Ramondenc, Y.;
Marsais, F.; Ple, N. Eur. J. Org. Chem. 2008, 14, 3129. (d) Ren, S.; Fang, Q.; Yu, F.; Bu, D. J.
Polym. Sci., Part A: Ploym. Chem. 2005, 43, 6554.
7

8. Examples of condensation of aromatic aldehydes with amidines, see: (a) Xie, F.; Chen. M.-M.;
Wang, X.-T.; Jiang, H.-F.; Zhang, M. Org. Biomol. Chem. 2014, 12, 2761. (b) Biswas, S.; Batra, S.
Eur. J. Org. Chem. 2012, 18, 3492. (c) Kumar, V.; Gupta, M. Mahajan, M. P. Can. J. Chem. 2006,
8
9
2
2
1
4, 453. (d) Haruki, E.; Inaike, T.; Imoto, E. Nippon Kagaku Zasshi 1966, 87, 206.
. Problem associated with aldehydes, see: (a) Sharama, G. V. R.; Robert, A. Res. Chem. Intermed.
013, 39, 3251. (b) Modak, A.; Deb, A.; Patra, S.; Rana, S.; Maity, S.; Maiti, D. Chem. Commun.
012, 48, 4253. (c) Iwai, T.; Fujihara, T.; Tsuji, Y. Chem. Commun. 2008, 44, 6215.
0. Recent examples of copper-catalyzed formation of imines, see: (a) Hu, Z.; Kerton, F. M. Org.
Biomol. Chem. 2012, 10, 1618. (b) Patil, R. D.; Adimurthy, S. Adv. Synth. Catal. 2011, 353, 1695.
1. (a) Brasche, G.; Buchwald, S. L. Angew. Chem. Int. Ed. 2008, 47, 1932. (b) Cooper, F. C.;
Partridge, M. W. J. Chem. Soc. 1953, 255.
2. Typical procedure for the synthesis of 2,4,6-triphenyl-1,3,5-triazine (2a): An oven-dried
1
1
microwave vial (10 mL) equipped with a magnetic stirring bar was charged with N-
benzylbenzamidine (105 mg, 0.5 mmol) and CuCl (2.47 mg, 5 mol%, 0.025 mmol). The vessel was
flushed with O
2
and then sealed with septum. Dry DMSO (1 mL) was added to the reaction vial
ο
using a syringe. The reaction mixture was heated at 100 C and stirred for 15 h. The reaction
mixture was allowed to reach room temperature and then poured into water (10 mL). This was
extracted with dichloromethane (20 mL). The aqueous layer was further extracted with
dichloromethane (2 x 10 mL). The combined organic extracts was washed with water (2 x 10 mL)
2 4
and dried with anhydrous Na SO . The solvent was removed under vacuum. The residue was
directly purified by flash chromatography on silica gel (230-400 mesh) using ethyl acetate-
petroleum ether mixture (1:19) as eluent to give 2,4,6-triphenyl-1,3,5-triazine 2a as white solid
(
0.06 g, 78%).
3. (a) Tanaka, H.; Shizu, K.; Nakanotani, H.; Adachi, C. Chem. Mater. 2013, 25, 3766. (b) Fink,
R.; Frenz, C.; Thelakkat, M.; Schmidt, H.-W. Macromolecules 1997, 30, 8177.
1
8

Previous methods:
NH2
Ar1 CHO
Cs
2
CO
3
+
Ar2
NH
NH2
NH
Require aldehydes or alcohols
DMSO
Ar1
N
Ar1
NH
[
Ru]-cat
DMSO
N
N
Ar1
OH
+
Ar2
Ar2
Ar2
N
Ar2
A
HN
Ar2
Ar1
NH
[
Cu]-cat, DMSO
This method does not require aldehydes or alcohols
Scheme 1. Methods accessing 2,4,6-triaryl-1,3,5-triazines from amidines.
9

a
Table 1. Optimization of the conditions for the copper-catalyzed cyclization of N-benzylbenzamidine 1.
Ph
HN
Ph
NH
CuCl (5 mol%)
N
N
Ph
DMSO (1 mL), O (1 atm)
2
Ph
N
Ph
0
1
00 C, 15 h
1a
2a
"
optimal conditions"
b
Entry
Catalyst (mol%)
Solvent (1 mL)
Yield (%)
1
2
3
4
5
6
7
8
9
CuI (5)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
52
78
47
37
40
15
20
trace
55
0
CuCl (5)
CuBr (5)
CuCl (5)
2
CuBr (5)
2
Cu(OAc) (5)
2
CuO (5)
CuSO .5H O (5)
4
2
CuCl (5)
10
11
12
CuCl (5)
CuCl (5)
CuCl (5)
CuCl (5)
CuCl (5)
CuCl (10)
CuCl (5)
HFIP
THF
16
trace
55
67
77
57
0
toluene
DMSO
DMSO
DMSO
DMSO
DMSO
c
13
c
14
15
d
16
17
ο
a] Reaction conditions: 1a (0.5 mmol), catalyst, O (1 atm), 100 C, 15 h.
[
2
[
b] Isolated yield of 2a.
c] Reaction carried out at 90 C (entry 13) and at 110 C (entry 14).
d] Reaction performed under an open air atmosphere, reaction completed in 36 h (entry 16).
ο
ο
[
[
10

a
Table 2. Synthesis of 2,4,6-triaryl-1,3,5-triazines from N-benzylbenzamidines.
Ar1
HN
Ar2
Ar1
NH
CuCl (5 mol %), O (1 atm)
2
N
N
ο
DMSO (1 mL), 100 C, 15 h
Ar2
N
Ar2
b
Yield (%)
Entry
Substrate 1
Product 2
1
2
1
2
3
4
5
6
7
8
9
1a: Ar = -C
6
H
5
, Ar = -C
6
H
5
2a
2b
2c
2d
2e
2f
78
76
75
71
68
84
80
82
84
79
1
2
1b: Ar = -C
H
, Ar = 4-Br-C
H
6
5
6
4
1
2
1c: Ar = -C
H
5
, Ar = 4-Cl-C
H
4
6
6
1
2
1d: Ar = -C
H
, Ar = 4-F-C
H
4
6
5
6
1
2
1e: Ar = -C
H
5
, Ar = 3-CF
-C H
6 4
6
3
1
2
1f: Ar = -C
H
5
, Ar = 4-OMe-C
H
6
6
4
1
2
1g: Ar = 4-OMe-C
H
, Ar = -C
H
5
2g
2h
2i
6
4
6
1
2
1h: Ar = 3,4-di-OMe-C
H
, Ar = -C
H
6
3
6
5
1
2
1i: Ar = 2,4,6-tri-OMe-C
H
2
, Ar = -C
H
6
6
5
1
2
1
0
1
1j: Ar = 4-Me-C
6
H
4
, Ar = -C
6
H
5
2j
1
2
c
1
1k: Ar = -C
6
H
5
, Ar =
2k
68
S
ο
a] Reaction conditions: Substrate (0.5 mmol) , CuCl (5 mol%), DMSO (1 mL), 100 C, O (1 atm), 15 h.
[
[
[
2
b] Yield of the isolated product.
c] Yield of 1,3,5-dihydrotriazine.
11

Ar2
NH
N
N
CuCl (5 mol%), O (1 atm)
2
Ar2
N
Ar1
0
DMSO (1 mL), 100 C, 15 h
Ar2
Ar1
H
N
2
1
1/4
O2
1
/ H O
4
H2
2
Ar2
NH
oxidative addition
Cu(I)Cl
NH
H
N
Ar2
N
Ar1
Cu(II)Cl
Ar2
N
Ar1
D
1
Ar CH NH
2
1/
1
2
H O / O
2
4
4
2
Ar1
Ar2
Ar2
H
N
Ar2
Ar1
N
NH
.
2
.
H N
..
H N HN
N
Ar1
HN
NH
Ar1
2
Ar2
Ar1
1
N
Ar2
N
Ar1
Ar2
N
A
B
C
Scheme 2. Proposed mechanism for the formation of 2,4,6-triaryl-1,3,5-triazines from N-benzylbenzamidines.
12

Table 1. Optimization of the conditions for the copper-catalyzed cyclization of N-
a
benzylbenzamidine 1.
Ph
HN
Ph
Ph
NH
CuCl (5 mol%)
N
N
DMSO (1 mL), O (1 atm)
2
Ph
N
Ph
o
1
00 C, 15 h
1a
2a
"
optimal conditions"
b
Entry Catalyst (mol%)
Solvent (1 mL)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
Yield (%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
CuI (5)
52
CuCl (5)
CuBr (5)
78
47
CuCl
2
(5)
(5)
37
CuBr
2
40
Cu(OAc)
CuO (5)
CuSO .5H
2
(5)
15
20
4
2
O (5)
trace
55
CuCl (5)
CuCl (5)
CuCl (5)
CuCl (5)
CuCl (5)
CuCl (5)
CuCl (10)
CuCl (5)
-
0
1
2
3
4
5
6
7
HFIP
0
THF
16
toluene
DMSO
DMSO
DMSO
DMSO
DMSO
trace
55
c
c
67
77
d
57
0
o
[
2
a] Reaction conditions: 1a (0.5 mmol), catalyst, O (1 atm), 100 C, 15 h.
13

[
[
[
b] Isolated yield of 2a.
c] Reaction carried out at 90 C (entry 13) and at 110 C (entry 14).
d] Reaction performed under an open air atmosphere, reaction completed in 36 h (entry 16).
o
o
14

a
Table 2. Synthesis of 2,4,6-triaryl-1,3,5-triazines from N-benzylbenzamidines.
Ar1
HN
Ar2
Ar1
NH
CuCl (5 mol %), O (1 atm)
2
N
N
ο
DMSO (1 mL), 100 C, 15 h
Ar2
N
Ar2
1
2
b
Entry
Substrate 1
Product 2
Yield (%)
1
1a: Ar = -C
2
, Ar = -C
1
2
3
4
5
6
7
8
9
6
H
5
6
H
5
2a
2b
2c
2d
2e
2f
78
1
1b: Ar = -C
2
, Ar = 4-Br-C
6
H
5
6
H
4
76
1
1c: Ar = -C
2
, Ar = 4-Cl-C
6
H
5
6
H
4
75
1
1d: Ar = -C
2
, Ar = 4-F-C
6
H
5
6
H
4
71
1
1e: Ar =-C
2
, Ar = 3-CF
6
H
5
3
-C
6
H
4
68
1
1f: Ar =-C
2
, Ar = 4-OMe-C
6
H
5
6
H
4
84
1
1g: Ar = 4-OMe-C
2
, Ar = -C
6
H
4
6
H
5
2g
2h
2i
80
1
1h: Ar = 3,4-di-OMe-C
2
, Ar = -C
6
H
3
6
H
5
82
1
1i: Ar = 2,4,6-tri-OMe-C
2
, Ar =-C
6
H
2
6
H
5
84
1
1j: Ar = 4-Me-C
2
, Ar = -C
1
1
0
1
H
6 4
H
6 5
2j
79
1
1k: Ar = -C
2
, Ar = thiophen-3-yl
c
H
6 5
2k
68
o
a] Reaction conditions: Substrate (0.5 mmol) , CuCl (5 mol%), DMSO (1 mL), 100 C,
[
atm), 15 h.
2
O (1
[
[
b] Yield of the isolated product.
c] Yield of 1,3,5-dihydrotriazine.
15