2,4,6-Trichloro-1,3,5-triazine as an efficient catalyst for synthesis of benzopyran derivatives under solvent-free conditions

Article abstract of DOI:10.1080/00397910802369604

An efficient and convenient procedure has been developed for the synthesis of benzopyran derivatives by one-pot condensation of substituted salicyaldehydes and substituted 1,3-hexanediones in the presence of a catalytic amount of 2,4,6-trichloro-1,3,5-tri

Full text of DOI:10.1080/00397910802369604

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2,4,6-Trichloro-1,3,5-triazine
as an Efficient Catalyst for
Synthesis of Benzopyran
Derivatives under Solvent-Free
Conditions
a
a
a
Peng Zhang , Yong-Dong Yu & Zhan-Hui Zhang
a
College of Chemistry and Material Science, Hebei
Normal University, Shijiazhuang, China
Version of record first published: 07 Nov 2008
To cite this article: Peng Zhang, Yong-Dong Yu & Zhan-Hui Zhang (2008): 2,4,6-
Trichloro-1,3,5-triazine as an Efficient Catalyst for Synthesis of Benzopyran
Derivatives under Solvent-Free Conditions, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 38:24,
4474-4479
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1
Synthetic Communications , 38: 4474–4479, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802369604
2
,4,6-Trichloro-1,3,5-triazine as an Efficient
Catalyst for Synthesis of Benzopyran Derivatives
Under Solvent-Free Conditions
Peng Zhang, Yong-Dong Yu, and Zhan-Hui Zhang
College of Chemistry and Material Science, Hebei Normal University,
Shijiazhuang, China
Abstract: An efficient and convenient procedure has been developed for the synth-
esis of benzopyran derivatives by one-pot condensation of substituted salicyalde-
hydes and substituted 1,3-hexanediones in the presence of a catalytic amount
of 2,4,6-trichloro-1,3,5-triazine (TCT, cyanuric chloride) under solvent-free
conditions.
Keywords: Benzopyran derivatives, 1,3-hexanedione, salicylaldehyde, solvent-free
condition, 2,4,6-trichloro-1,3,5-triazine
Benzopyran and its derivatives have attracted considerable attention
from organic and medicinal chemists because of their useful biological
[
and pharmacological properties, such as anti-estrogenic activity, anti-
1]
[2]
[3]
microbial activity, insulin-sensitizing activities, selective thrombin
[
4]
[5]
THR) inhibitors, hypoglycemic activity, and antibacterial activity.
[6]
(
[
7]
Some benzopyrans can be useful as selective estrogen receptors. Thus,
the synthesis of a variety of benzopyran heterocyclic molecules is desir-
able. Recently, benzopyran derivatives have been synthesized by the reac-
tion of substituted salicyaldehydes with dimedone catalyzed by
[
8]
[9]
KF=Al O or triethylbenzylammoium chloride (TEBA). Considering
2
3
the importance and wide range applications of the compounds, an easy
Received April 28, 2008.
Address correspondence to Zhan-Hui Zhang, College of Chemistry and
Material Science, Hebei Normal University, Shijiazhuang, China. E-mail: zhanhui@
mail.nankai.edu.cn
4
474

Synthesis of Benzopyran Derivatives
4475
Scheme 1.
and practical method for the preparation of these compounds has still
remained a challenging task.
In recent years, 2,4,6-trichloro-1,3,5-triazine (TCT, cyanuric chlor-
ide) has been used in organic synthesis because it is stable, nonvolatile,
[
10–13]
inexpensive, commercially available, and easy-to-handle reagent.
In continuation of our work on the applications of cheap and ecofriendly
materials as catalysts for development of new synthetic methodolo-
[
14–16]
gies,
we herein report a new, convenient, and one-reaction step
synthesis of benzopyran derivatives by treatment of substituted salicyal-
dehydes and substituted 1,3-hexanedione in the presence of catalytic
amount of TCT under solvent-free conditions (Scheme 1).
To obtain some preliminary information on this synthetic reaction,
initial experiments were performed with salicyaldehyde (1a) and 5,5-
1
dimethyl-1,3-cyclohexanedione (2b, R ¼ Me) as model substrates. When
1
a (2 mmol) was treated with 2b (4 mmol) in the presence of a catalytic
ꢀ
amount of TCT (10 mol%) at 120 C, the desired product 3a was obtained
in 93% yield. The effect of amount of catalyst on the yield and rate was
also investigated. It was found that 10 mmol% of catalyst was enough for
a fairly high yield. The lesser amounts gave a low yield even after a long
reaction time, and more amounts could not cause the obvious increase
for the yield of product. Meanwhile, we also tested the effect of reaction
temperature on the catalyzed reaction. When the reaction was carried out
ꢀ
at 120 C, maximum yield was obtained in a short reaction period.
To explore the scope and limitation of this reaction, a variety of sub-
strates were submitted to this reaction condition, and the results are sum-
marized in Table 1. It is evident that electron-rich and electron-deficient
salicyaldehydes as well as 2-hydroxy-naphthalene-1-carbaldehyde reacted
smoothly with substituted 1,3-hexanediones to produce high yields of pro-
ducts. All the products were characterized by comparison of their analytical
1
data (IR and H NMR) and melting points with those of authentic samples.
In summary, we have report a novel, mild, and highly efficient pro-
cedure for the synthesis of benzopyran derivatives. The use of inexpensive

4476
P. Zhang, Y.-D. Yu, and Z.-H. Zhang
Table 1. Synthesis of 1-oxo-hexahydroxanthene derivatives catalyzed by cyanuric
chloride
ꢀ
Mp ( C)
1
a
Time (h) Yield (%) Found Reported
Entry
Aldehydes
R
[
[
[
9]
a
b
c
d
e
f
2–OHC H CHO
6
CH3
2.5
2
2
2
3
3
3
3
3
93
90
89
91
90
94
94
91
95
95
210–212 206–208
229–231 230–231
223–225 222–224
225–227
4
17]
8]
2–OH–3–MeOC
2–OH–5–MeC
2–OH–5–FC H CHO
6
H
4
CHO CH
CHO CH
3
3
6
H
4
CH3
6
4
[
[
[
[
[
[
9]
9]
9]
9]
9]
9]
2–OH–5–ClC
2–OH–5–BrC
6
H
4
CHO
CHO
CH
CH
CHO CH
3
3
3
236–238 238–239
251–253 253–255
203–205 205–207
236–237 235–237
258–260 260–262
240–242 245–248
6
H
4
g
h
i
2–OH–5–NO
2
C
6
H
4
2–OH–3,5–Cl C H CHO CH3
6
2
4
2–OH–3,5–Br
2
C
6
H
4
CHO CH
3
J
2-Hydroxy-naphthalene-1- CH
carbaldehyde
3
2
[
[
[
[
[
[
9]
9]
9]
9]
9]
9]
k
l
2–OHC
2–OH–5–ClC
2–OH–5–BrC H CHO
2–OH–3,5–Cl
2–OH–3,5–Br
2-Hydroxy-naphthalene-1- H
carbaldehyde
6
H
4
CHO
H
H
H
H
H
3
3
3
3
2.5
2
90
92
93
94
94
90
245–247 244–246
244–245 245–247
238–239 235–236
255–256 254–256
258–259 255–257
217–219 216–218
6
H
4
CHO
m
n
o
p
6
4
2
C
6
4
H CHO
CHO
2
C
6
H
4
a
Isolated yield.
and easily available catalyst, high yield, and relatively short reaction time
are the attractive features of this method.
EXPERIMENTAL
Melting points were determined on an X-4 apparatus and are uncor-
rected. IR spectra were obtained using Shimadzu FTIR-8900 spectro-
1
meter. H NMR spectra were recorded with a Varain Mercury Plus
400 spectrometer using TMS as internal standard. Elemental analyses
were performed on Vario EL III CHNOS elemental analyzer.
Typical Procedure
A mixture of substituted salicylaldehyde (2 mmol), substituted 1,3-hexa-
nediones (4 mmol), and TCT (0.2 mmol) were mixed and stirred for
ꢀ
5
min at room temperature, and then temperature was raised to 120 C

Synthesis of Benzopyran Derivatives
4477
and maintained for the specified time (Table 1). After completion of the
reaction (monitored by thin-layer chromatography, TLC), the reaction
ꢀ
mixture was diluted with water (10 mL) and stirred for 5 min at 80 C.
The resulting solid products were collected by filtration and were recrys-
tallized from 95% ethanol.
Data
9-(2-Hydroxy-4,4-dimethyl-6-oxo-cyclohex-1-enyl)-3,3-dimethyl-2,3,4,9-
tetrahydro-xanthen-1-one (3a)
IR (KBr): n ¼ 3188, 2952, 1643, 1593, 1488, 1375, 1313, 1261, 1232, 1188,
ꢁ
1 1
024, 1008, 756, 578 cm . H NMR (400 MHz, CDCl ) d ppm: 0.98 (s,
1
3
6
7
H), 1.02 (s, 3H), 1.12 (s, 3H), 1.95–2.70 (m, 8H), 4.65 (s, 1H), 6.99–
.18 (m, 4H), 10.43 (s, 1H, OH). Anal. calcd. for C H O : C, 75.38;
H, 7.15. Found: C, 75.50; H, 6.92.
2
3
26
4
9-(2-Hydroxy-4,4-dimethyl-6-oxo-cyclohex-1-enyl)-5-methoxy-3,3-
dimethyl-2,3,4,9-tetrahydro-xanthen-1-one (3b)
IR (KBr): n ¼ 3213, 2952, 1641, 1581, 1483, 1375, 1313, 1271, 1230, 1209,
ꢁ
1 1
1
3
3
6
095, 1024, 758 cm . H NMR (400 MHz, CDCl ): d ¼ d ppm: 0.97 (s,
3
H), 0,99 (s, 3H), 1.02 (s, 3H), 1.12 (s, 3H), 1.96–2.70 (m, 8H), 3.88 (s,
H), 4.66 (s, 1H), 6.59 (d, J ¼ 8.0 Hz, 1H), 6.76 (d, J ¼ 8.0 Hz, 1H),
.94 (t, J ¼ 8.0 Hz, 1H), 10.44 (s, 1H, OH). Anal. calcd. for C H O :
2
4
28
5
C, 72.70; H, 7.12. Found: C, 72.42; H, 7.38.
7-Fluoro-9-(2-hydroxy-4,4-dimethyl-6-oxo-cyclohex-1-enyl)-3,3-
dimethyl-2,3,4,9-tetrahydro-xanthen-1-one (3d)
IR (KBr): n ¼ 3215, 2960, 2813, 1643, 1627, 1595,1496, 1427, 1379, 1311,
ꢁ1
1
. H NMR (400 MHz,
1
259, 1194, 1143, 1024, 1006, 819, 748 cm
CDCl ): d ¼ 0.99 (s, 3H), 1.01 (s, 6H), 1.12 (s, 3H), 1.97–2.60 (m, 8H),
3
4
.62 (s, 1H), 6.70 (d, J ¼ 7.6 Hz, 1H), 6.82–6.87 (m, 1H), 6.98 (dd,
23 25 4
J ¼ 8.4, 4.8 Hz, 1H), 10.50 (s, 1H, OH). Anal. calcd. for C H FO : C,
7
1.86; H, 6.55. Found: C, 71.68; H, 6.40.
7
-Bromo-9-(2-hydroxy-4,4-dimethyl-6-oxo-cyclohex-1-enyl)-3,3-
dimethyl-2,3,4,9-tetrahydro-xanthen-1-one (3f)
IR (KBr): n ¼ 3421, 3107, 2958, 1624, 1477, 1377, 1232, 1182, 1153, 1039,
ꢁ
1 1
89, 594 cm . H NMR (400 MHz, CDCl ): d ¼ 0.98 (s, 3H), 1.01 (s, 6H),
8
3

4478
P. Zhang, Y.-D. Yu, and Z.-H. Zhang
1
7
6
.12 (s, 3H), 1.98–2.60 (m, 8H), 4.60 (s, 1H), 6.90 (d, J ¼ 8.4 Hz, 1H),
.12–7.26 (m, 2H), 10.43 (s, 1H, OH). Anal. calcd. for C H BrO : C,
25
2
3
4
2.03; H, 5.66. Found: C, 62.25; H, 5.48.
ACKNOWLEDGMENT
We are grateful for financial support from Hebei Normal University
L20061314), the Nature Science Foundation of Hebei Province (B200800
149), and the Natural Science Foundation of Hebei Education Department
2006318).
(
0
(
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