The direct arylation of 1,3,5-triazin-2,4(1H,3H)-dione

Article abstract of DOI:10.1016/j.tetlet.2010.01.086

Direct introduction of non-activated arenes to 1,3,5-triazin-2,4(1H,3H)-dione in the presence of AlCl₃ is described.

Full text of DOI:10.1016/j.tetlet.2010.01.086

Tetrahedron Letters 51 (2010) 1717–1718
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Tetrahedron Letters
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The direct arylation of 1,3,5-triazin-2,4(1H,3H)-dione
a
a,b
Ilya N. Egorov a, , Vladimir L. Rusinov , Oleg N. Chupakhin
*
a Urals State Technical University, Department of Organic Chemistry, Mira St. 19, Ekaterinburg 620002, Russia
b Institute of Organic Synthesis of Russian Academy of Sciences, S. Kovalevskoy St., 22, Ekaterinburg 620041, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
Direct introduction of non-activated arenes to 1,3,5-triazin-2,4(1H,3H)-dione in the presence of AlCl3 is
Received 26 October 2009
Revised 24 December 2009
Accepted 25 January 2010
Available online 1 February 2010
described.
Ó 2010 Elsevier Ltd. All rights reserved.
New synthetic approaches to derivatives of 1,3,5-triazines are of
significant interest because these compounds display various bio-
logical activities. Almitrine is a well-known remedy for respiratory
insufficiency and triazine herbicides are the most commonly used
to control weeds during the production of corn, sorghum and sug-
arcane in the USA.1
O
R
+
+
H
N
HN
R
N
H
2-6
O
O
Cl
1,3,5-Triazines are
p-deficient heteroaromatic compounds and
display activity in reactions with a variety of nucleophiles.1 Along
with aromatic nucleophilic ipso-substitution reactions (SNAripso),1,2
there are examples of nucleophilic addition to the C@N bond of
1,3,5-triazine-2,4(1H,3H)-dione.3 This offers the possibility to
insert a vast number of nucleophiles on the triazine substrate
which does not possess good leaving groups. Arene nucleophiles
are of interest because the formation of new C–C bonds between
arenes and hetarenes is an important tool in modern organic syn-
O
HN
O
Cl
H
N
N
R
+ AlCl3
HN
R
N
H
N
H
R
O
O
7
8
1
R
+
R
H
N
R
HN
O
R
thesis.4,5 Besides well-known reactions between
p-deficient heta-
N
H
renes and arenes with strong electron-donating substituents (OR,
NR1R2),4 there are a few examples of reactions with unactivated
arene nucleophiles. Girke earlier described reactions of pyrimi-
dine6a with perylene, and quinazoline6b with naphthalene, anthra-
cene and mesitylene in the presence of trifluoroacetic acid. There is
only one example of the reaction of benzene in the capacity of a
nucleophile with 5,6-diphenyl-3-hydroxy- and 5,6-diphenyl-3-
mercapto-1,2,4-triazines in the presence of AlCl3.7
R
Scheme 1.
Table 1
Entry
Product
R
Equiv of AlCl3
T (°C)
Time (h)
Yield (%)
Here, we report a one-step method for the direct introduction of
arenes on 1,3,5-triazine-2,4(1H,3H)-dione (1) by means of C–C
bond formation in the presence of aluminium chloride. The reac-
tions were carried out in the presence of various arenes without
any solvent, (Scheme 1).
1
2
3
4
5
6
7
8
9
10
11
12
13
2
CH3
CH3
CH3
H
H
Br
Br
Cl
Cl
NMe2
CH3
CH3
CH3
3.0
3.0
1.2
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
25
110
110
25
80
25
156
25
132
25
25
162
25
18
3
3
18
3
18
3
18
3
18
18
3
45 (67)a
61
27
34
59
21
45
30
40
2
2
3
3
4
4
5
5
6
7
7
8
The structures of products 2–8 (Table 1) were confirmed by
analytical methods including X-ray analysis of compound
8
(Fig. 1). In addition, 6-phenyl[1,3,5]triazinan-2,4-dione (3) was
22
44 (63)a
52
18
37 (65)a
* Corresponding author. Tel.: +7 343 3754501; fax: +7 343 3740458.
E-mail address: i.n.egorov@gmail.com (I.N. Egorov).
a
Yield of crude product.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.01.086

1718
I. N. Egorov et al. / Tetrahedron Letters 51 (2010) 1717–1718
The proposed reaction mechanism includes initial formation of
a complex between 1,3,5-triazine-2,4(1H,3H)-dione and AlCl3.
Next, the activated triazine attacks the arene resulting in the for-
mation of a
r-complex of possible structure A; loss of a proton re-
sults in the formation of the aromatic system (Scheme 2).
In conclusion, a simple and convenient method for the addition
of non-activated arenes to
p-deficient heterocyclic compounds is
described. This method may serve as an alternative to using acti-
vated (het)arenes as coupling agents in the presence of transition
metal catalysts (including Suzuki, Kumada, Ullmann reactions)
for C–C bond formation between arenes and hetarenes.5
Acknowledgement
This work was supported by the program of the Russian Feder-
ation President for government support of young scientists, MK-
1157.2009.3.
Figure 1. ORTEP diagram of compound 8.9
Supplementary data
+
O
HN
O
O
HN
O
-
AlCl3
N
N
+ AlCl3
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.01.086.
N
H
N
H
References and notes
1
R
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O
HN
O
H
R
H
N
H
+
- H+
+ H+
H
N
H
A
O
H
N
R
HN
O
N
H
R = H, CH3, Cl, Br, NMe2
2-8
Scheme 2.
5. (a) Hassan, J.; Sevignon, M.; Gozzi, C.; Shulz, E.; Lemaire, M. Chem. Rev. 2002,
102, 1359; (b) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174.
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112, 1348.
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9. Crystallographic data have been deposited with the Cambridge
Crystallographic Data Centre (deposition number CCDC 743053). These data
can be obtained via: www.ccdc.cam.ac.uk/data_request/cif.
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prepared using a known method.8 The 1H NMR spectra of com-
pound 3 synthesized by the two different methods were the same.
Investigation of the reaction conditions indicated that increas-
ing the temperature led to higher yields in each case. The yields
of products are not optimized at present. Reported methods give
product 3 in similar yields, 60%,8 58%10 and 54%.11