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Chemistry Letters Vol.38, No.12 (2009)
Insertion of Arynes into Carbon–Chlorine Bonds of Chlorotriazines
Hiroto Yoshida,ꢀ Yasuhiro Mimura, and Joji Ohshita
Department of Applied Chemistry, Graduate School of Engineering, Hiroshima University,
Higashi-Hiroshima 739-8527
(Received September 16, 2009; CL-090835; E-mail: yhiroto@hiroshima-u.ac.jp)
Table 1. Insertion of arynes into cyanuric chloridea
A variety of chlorotriazines were found to undergo insertion
of arynes at their carbon–chlorine bonds, leading to formation of
triarylated triazines in a straightforward manner.
Cl
N
Cl
R
N
N
Cl
N
R
Cl
1a
+
N
KF
18-Crown-6
In view of a considerable demand for efficacious methods
for synthesizing complex organic halides that can be trans-
formed into diverse molecules via cross-coupling reaction etc.,
development of insertion reactions of unsaturated carbon–car-
bon compounds into a carbon–halogen ꢀ-bond, which enable a
carbon–carbon and a carbon–halogen bonds to be constructed si-
multaneously, has been an essential subject in synthetic organic
chemistry (eq 1).1 In this context, we have already disclosed that
a carbonyl carbon–chlorine (or bromine) ꢀ bond of acid chlo-
rides (or bromides) is facilely added across a carbon–carbon tri-
ple bond of arynes, demonstrating that a carbon and a halogen
functional groups can be installed into neighboring positions
of aromatic rings all at once (eq 2).2–4 Since six-membered nitro-
gen-heteroaromatic compounds bear marked electronic and
structural resemblances to carbonyl compounds, we envisaged
that those with a halogen substituent should participate in the re-
action with arynes, providing a new method for constructing
aryl–heteroaryl bonds. Herein we report on the insertion reaction
of arynes into carbon–chlorine bonds of chlorotriazines, which
offers a direct approach to triaryltriazines.
N
R
Cl
3
THF
TMS
4
Cl
R
5
OTf
6
2
3
Entry
R
Temp/ꢁC Time/h Yield/%b
3
1
2
3
4
5
6
H (2a)
3,6-Me2 (2b)
4,5-Me2 (2c)
0
0
8
23
2
35
33
27
31
20
14
3aa
3ab
3ac
3ad
3ae
3af
50
50
50
50
4,5- –(CH2)3– (2d)
4,5- –(CH2)4– (2e)
4,5- –(CH)4– (2f)
6
3
6.5
aThe reaction was carried out in THF (2 mL) using 1a (0.1 mmol), 2
(0.3 mmol), KF (0.6 mmol), and 18-crown-6 (0.6 mmol). bIsolated yield
based on 1a.
TMS
Cl
TMS
Cl
from 2f
Cl
N
Cl
N
N
OH
N
OH
ð1Þ
ð2Þ
N
N
Cl
Cl
from 2e
from 2d
A reaction of cyanuric chloride (2,4,6-trichloro-1,3,5-tri-
azine, 1a) with in situ-generated benzyne (from 2a5 and KF/
18-crown-6) was initially carried out in THF at 0 ꢁC to afford
a 35% yield of 2,4,6-tris(2-chlorophenyl)-1,3,5-triazine (3aa),
in which three aryl–heteroaryl bond forming processes took
place via benzyne insertion into all of the carbon–chlorine bonds
of 1a (Entry 1, Table 1). Substituted arynes such as 3,6-di-
methylbenzyne (from 2b) or 4,5-dimethylbenzyne (from 2c)
could also take part in the reaction, giving the respective prod-
ucts (3ab or 3ac) in 33 or 27% yield (Entries 2 and 3), and
furthermore, 1a underwent the insertion of three molar equiva-
lents of cycloalkane-condensed arynes (from 2d or 2e) or 2,3-
naphthalyne (from 2f) (Entries 4–6). In some cases, ortho-
chloro(trimethylsilyl)arenes and bis(2-chloroaryl)triazines6 aris-
ing from the insertion of two molar equivalents of arynes were
produced as by-products (Figure 1).
Figure 1. By-products formed in the reaction of 1a with arynes.
triazine (1b) were added to benzyne to furnish 3aa as the sole
product in 58% yield (Entry 1). Dichlorotriazines having 3-cya-
nophenyl (1c) or 4-(trifluoromethyl)phenyl moiety (1d) reacted
with two molar equivalents of benzyne as well, offering moder-
ate yields of the respective products (3ca or 3da) (Entries 2 and
3), and the insertion of benzyne also occurred with aryldichloro-
triazines 1e–1g, although the yields were rather low (Entries 4–
6). Treatment of alkoxydichlorotriazines (1h or 1i) with benzyne
gave a mixture of diarylated (3ha or 3ia) and monoarylated tri-
azines (4ha or 4ia) in approximately equal ratios (Entries 7 and
8), and moreover, no trace of the insertion product was formed in
the reaction of aminodichlorotriazine 1j (Entry 9), which implies
that introduction of an electron-donating group into the triazine
ring retards the reaction.
Next we investigated the reaction of dichlorotriazines as
shown in Table 2. Similarly to the case of 1a, both of the car-
bon–chlorine bonds of 2-(2-chlorophenyl)-4,6-dichloro-1,3,5-
In marked contrast to the above results, monochlorotriazines
did not undergo the insertion of benzyne at all (Scheme 1).7 In
particular, it should be noted that 2,4-bis(2-chlorophenyl)-6-
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