Clean, one-pot synthesis of 4H-pyran derivatives catalyzed by hexadecyltrimethyl ammonium bromide in aqueous media

Article abstract of DOI:10.1081/SCC-200064898

An efficient and convenient synthetic route to 4H-pyran derivatives in water in the presence of hexadecyltrimethyl ammonium bromide (HTMAB) as catalyst is described. This method provides several advantages such as environment friendliness, high yields, an

Full text of DOI:10.1081/SCC-200064898

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Clean, One‐Pot Synthesis of
4H‐Pyran Derivatives Catalyzed
by Hexadecyltrimethyl
Ammonium Bromide in
Aqueous Media
Tong‐Shou Jin a , Li‐Bin Liu a , Ying Zhao a
Tong‐Shuang Li a
&
a Department of Chemistry , College of Chemistry
and Environmental Science, Hebei University ,
Baoding, China
Published online: 16 Aug 2006.
To cite this article: Tong‐Shou Jin , Li‐Bin Liu , Ying Zhao & Tong‐Shuang Li (2005)
Clean, One‐Pot Synthesis of 4H‐Pyran Derivatives Catalyzed by Hexadecyltrimethyl
Ammonium Bromide in Aqueous Media, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 35:14, 1859-1863,
DOI: 10.1081/SCC-200064898
To link to this article: http://dx.doi.org/10.1081/SCC-200064898
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Synthetic Communicationsw, 35: 1859–1863, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200064898
Clean, One-Pot Synthesis of 4H-Pyran
Derivatives Catalyzed
by Hexadecyltrimethyl Ammonium
Bromide in Aqueous Media
Tong-Shou Jin, Li-Bin Liu, Ying Zhao, and Tong-Shuang Li
Department of Chemistry, College of Chemistry and Environmental
Science, Hebei University, Baoding, China
Abstract: An efficient and convenient synthetic route to 4H-pyran derivatives in water
in the presence of hexadecyltrimethyl ammonium bromide (HTMAB) as catalyst is
described. This method provides several advantages such as environment friendliness,
high yields, and a simple workup procedure. In addition, water was chosen as a green
solvent.
Keywords: Bisarylidenecyclohexanone, green synthesis, 4H-pyran derivatives,
HTMAB
INTRODUCTION
With the increasing environmental concerns and the regulatory constraints
faced by the chemical and pharmaceutical industries, development of environ-
mentally benign organic reactions has become a crucial and demanding
research area in modern organic chemical research.[1] Therefore, more and
more chemists are devoted to the researching “green synthesis,” which
means the reagent, solvent, and catalyst are environmentally friendly in the
organic chemical reactions. Recently, organic reactions in water without use
of harmful organic solvents have attracted much attention, because water is
Received in Japan January 11, 2005
Address correspondence to Tong-Shou Jin, Department of Chemistry, College of
Chemistry and Environmental Science, Hebei University, No. 88 Hezuo Road,
Baoding 071002, Hebei Province, China. E-mail: orgsyn@mail.hbu.edu.cn
1859

1860
T.-S. Jin et al.
a cheap, safe, and environmentally benign solvent.[2] In the course of our
investigations to develop new synthetic methods in water, we examined the
synthesis of 4H-pyran derivatives in water, as a green solvent.
Pyran derivatives occupy an important place in the realm of natural and
synthetic organic chemistry because of their biological and pharmacological
properties as antisterility and anticancer agents.[3] In addition, polyfunctiona-
lized 4H-pyrans are a common structural unit in a number of natural
products.[4] Moreover, 2-amino-3-cyano-4H-pyrans possess photochemical
activity.[5] These findings stimulated our interest in the synthesis of hetero-
cyclic derivatives of these ring systems.
As a good phase-transfer catalyst, hexadecyltrimethyl ammonium
bromide (HTMAB) has been used in a number of organic reactions.
However, the use of HTMAB as a catalyst in the synthesis of 4H-pyran deriva-
tives has not been reported. In this article, we report a general and highly
efficient route for the synthesis of 4H-pyran derivatives using an inexpensive
and commercially available HTMAB as catalyst. This a novel, one-pot com-
bination using water as a green solvent not only preserves the simplicity but
also consistently gives the corresponding products in good to excellent
yields (Scheme 1).
In a typical experimental procedure, a solution of bisarylidenecyclohex-
anone 1 and malononitrile 2 in water was heated in the presence of a
catalytic amount of HTMAB, and the corresponding 4H-pyran derivatives 3
were obtained in good to excellent yields. The results are summarized in
Table 1.
The catalyst plays a crucial role in the success of the reaction in terms of
the rate and the yields. To test the catalysts, the reaction of bisbenzalidenecy-
clohexanone and malononitrile in water was selected as a model reaction.
Among the catalysts tested, HTMAB was found to be the most efficient
catalyst. The catalysts we tested, DBSA (dodecylbenesulfonic acid), TBAB
(tetrabutylammonium bromide) and TEBA (tetraethylammonium bromide),
did not give products. HTMAB formed a white turbid reaction mixture,
whereas TBAB and TEBA formed two immiscible layers. This indicates
that the long alkyl chain of HTMAB is necessary for the formation of the
colloidal dispersion that is assumed to lead to efficient catalysis. We
Scheme 1.

Synthesis of 4H-Pyran Derivatives
1861
Table 1. Synthesis of 4H-pyran derivatives catalyzed by HTMAB in aqueous media
Mp (8C)
Yielda
(%)
Entry
Ar
n
Product
Found
Reported
1
2
3
4
5
6
7
8
C6H5 1a
1
1
1
1
1
1
0
0
3a
3b
3c
3d
3e
3f
93
80
77
87
82
76
78
85
230–231
237–238
201–202
215–216
161–162
216–218
227–228
213–214
228–230[6]
237–238[7]
—
217–219[6]
162–163[7]
—
228–230[7]
214–215[7]
2-ClC6H4 1b
3-ClC6H4 1c
4-ClC6H4 1d
4-CH3C6H4 1e
4-NO2C6H4 1f
C6H5 1g
3g
3h
2-ClC6H4 1h
aIsolated yield.
examined several experiments and found that the amount of the catalyst also
had a crucial effect on these conversions. For example, bisbenzalidenecyclo-
hexanone reacted with malononitrile in the presence of 1 mol% HTMAB to
give the product 3a in quantitative yield (66%) in refluxing water after 8 h
of reaction time. Increasing the catalyst to 5 and 10 mol% results to
increase the reaction yields 84% and 93% respectively. Use of merely
10 mol% HTMAB in refluxing water is sufficient to push the reaction
forward. Higher amounts of the catalyst did not improve the results to a
greater extent. Therefore, 10 mol% HTMAB was chosen as a quantitative
catalyst for the reactions.
The catalyst could be reused five times for the synthesis of 3a without sig-
nificant loss of activity. The results are summarized in Table 2. In addition, it
must be pointed out that all of these reactions were carried out in water.
The formation of the compounds 3 was assumed to proceed via formation
of a Michecal adduct intermediate followed by cyclization according to
Scheme 2. A bisarylidenecyclohexanone 1 was firstly condensed with malono-
nitrile 2 to afford the intermediate 4; this step can be regarded as a Michael
addition. Then, the intermediate 5 cyclized by nucleophilic attack of the OH
Table 2. Reuse of the catalyst for the
synthesis of 3a catalyzed by HTMAB
Entry
Yield (%)
1
2
3
4
5
93.0
92.7
92.0
91.7
90.9

1862
T.-S. Jin et al.
Scheme 2.
group on the cyano (CN) moiety and gave the intermediate 6. Finally, the
expected products 3 were afforded (5 ! 6 ! 3). In this process, HTMAB
could promote these reactions as an emulsifier.
In conclusion, we have described a general and highly efficient procedure
for the preparation of 4H-pyran derivatives by catalyzed HTMAB, in water
cooler than 1108C. In addition, it is possible to apply the tenets of green
chemistry to the generation of interesting products using aqueous media
methods that are less expensive and less toxic than those with organic
solvents. Moreover, the procedure offers several advantages including high
yields, operational simplicity, cleaner reactions, and minimal environmental
effects, which makes it a useful and attractive process for the synthesis of
these compounds.
EXPERIMENTAL
The new compounds prepared were characterized by 1H NMR, IR, and
elemental analysis and are described in the experimental section. IR spectra
1
were recorded on a Bio-rad FIS-40 spectrometer (KBr). H NMR spectra
were measured on an AVAVCE-400 spectrometer using TMS as internal
standard and CDCl3 as solvent.
General Procedure for 2-Amino-3-cyano-4H-pyran Derivatives
A mixture of the bisarylidenecyclohexanone 1 (1 mmol), malononitrile 2
(1 mmol), and HTMAB (10 mol%) in water (20 mL) was stirred at 1108C
for 8 h. Then, the mixture was cooled to room temperature, the solid was

Synthesis of 4H-Pyran Derivatives
1863
filtered off, and it was washed with H2O (40 mL). The crude products were
purified by recrystallization with ethanol (95%). Data of some compounds
are shown:
1
3c. H NMR (CD3Cl) d (ppm) 1.58–1.70 (m, 2H, CH2), 1.94–2.07
(m, 2H, CH2), 2.55–2.74 (m, 2H, CH2), 3.98 (s, 1H, CH), 4.58 (s, 2H,
NH2), 6.83 (s, 1H, CH55), 7.15–7.33 (m, 8H, 2 ꢀ C6H4); IR (KBr),
n(cm21) 3461, 3323, 2924, 2846, 2194, 1671, 1637, 1595, 1415, 1129.
Anal. calcd. for C23H18Cl2N2O: C, 67.48; H, 4.40; N, 6.84. Found: C,
67.35; H, 4.46; N, 6.92.
3f. 1H NMR (CD3Cl) d (ppm) 1.58–1.71 (m, 2H, CH2), 1.96–2.09
(m, 2H, CH2), 2.63–2.74 (m, 2H, CH2), 4.17 (s, 1H, CH), 4.67 (s, 2H,
NH2), 6.96 (s, 1H, CH55), 7.46–8.25 (m, 8H, 2 ꢀ C6H4); IR
(KBr), n(cm21) 3484, 3373, 2931, 2188, 1667, 1632, 1590, 1514, 1411,
1261, 1131. Anal. calcd. for C23H18N4O5: C, 64.19; H, 4.19; N, 13.02.
Found: C, 64.08; H, 4.11; N, 13.15.
ACKNOWLEDGMENT
This project was supported by the National Natural Science Foundation of
China, Educational Ministry of China, Educational Department of Hebei
Province, and Science and Technology Commission of Hebei Province.
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