Lithium bromide as a mild, efficient, and recyclable catalyst for the one-pot synthesis of tetrahydro-4H-chromene derivatives in aqueous media

Article abstract of DOI:10.1080/00397910903007079

A simple, efficient, one-pot method has been developed for the synthesis of tetrahydro-4H-chromene derivatives by concurrent reaction of aryl aldehydes, active methylene compounds, and 1,3-cyclohexanedins using a catalytic amount of lithium bromide in aqueous media. The present approach offers several advantages such as shorter reaction times, good yields, low cost, recycling of the catalyst, and simple workup. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910903007079

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Lithium Bromide as a Mild, Efficient,
and Recyclable Catalyst for the One-Pot
Synthesis of Tetrahydro-4H-Chromene
Derivatives in Aqueous Media
Wen-Bo Sun a , Peng Zhang a , Jia Fan a , Shao-Hua Chen a & Zhan-
Hui Zhang a
a College of Chemistry and Material Science, Hebei Normal
University, Shijiazhuang, China
Published online: 03 Feb 2010.
To cite this article: Wen-Bo Sun , Peng Zhang , Jia Fan , Shao-Hua Chen & Zhan-Hui Zhang
(2010) Lithium Bromide as a Mild, Efficient, and Recyclable Catalyst for the One-Pot Synthesis
of Tetrahydro-4H-Chromene Derivatives in Aqueous Media, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 40:4, 587-594, DOI:
10.1080/00397910903007079
To link to this article: http://dx.doi.org/10.1080/00397910903007079
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Synthetic Communications1, 40: 587–594, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903007079
LITHIUM BROMIDE AS A MILD, EFFICIENT, AND
RECYCLABLE CATALYST FOR THE ONE-POT
SYNTHESIS OF TETRAHYDRO-4H-CHROMENE
DERIVATIVES IN AQUEOUS MEDIA
Wen-Bo Sun, Peng Zhang, Jia Fan, Shao-Hua Chen, and
Zhan-Hui Zhang
College of Chemistry and Material Science, Hebei Normal University,
Shijiazhuang, China
A simple, efficient, one-pot method has been developed for the synthesis of tetrahydro-4H-
chromene derivatives by concurrent reaction of aryl aldehydes, active methylene com-
pounds, and 1,3-cyclohexanedins using a catalytic amount of lithium bromide in aqueous
media. The present approach offers several advantages such as shorter reaction times, good
yields, low cost, recycling of the catalyst, and simple workup.
Keywords: Aqueous media; 4H-chromene; lithium bromide; multicomponent reaction; one-pot synthesis
INTRODUCTION
The development of new methodologies for the synthesis of 4H-chromenes is a
subject of continuous interest to synthetic=medicinal chemists because their deriva-
tives have versatile biological and medicinal properties[1–3] and are widely present
in various biologically active natural products.[4] Some 4H-chromene derivatives
bearing a nitrile functionality, especially 2-amino-4-aryl-5-oxo-5,6,7,8-tetrahydro-
4H-chromene-3-carbonitriles, are synthetic precursors in medical synthesis[5] and
display potent in vitro antileishmanial activity.[6]
The widespread interest in the 4H-chromene-containing structures has led
to extensive studies of their synthesis. The known procedures for the synthesis
of 4H-chromene derivatives employ a three-component reaction of aryl alde-
hydes, active methylene compounds, and 1,3-cyclohexanedins under various
reaction conditions. The conventional reported methods for synthesis of
4H-chromenes involve use of organic solvents such as dimethylsulfoxide[7]
and dimethylformamide.[8] Several improved procedures have been reported
using a variety of catalysts such as tetra-methyl ammonium hydroxide (TMAH),[9]
tetrabutylammonium fluoride (TBAF),[4] triethylbenzylammonium chloride
(TEBA),[10] sodium selenate,[11] rare-earth perfluorooctanoate [RE(PFO)3],[12]
Received January 16, 2009.
Address correspondence to Zhan-Hui Zhang, College of Chemistry and Material Science, Hebei
Normal University, Shijiazhuang, China. E-mail: zhanhui@126.com
587

588
W.-B. SUN ET AL.
Scheme 1. Synthesis of tetrahydro-4H-chromene derivatives catalyzed by lithium bromide.
D,L-proline,[13]
(S)-proline,[14]
hexadecyltrimethyl
ammonium
bromide
(HTMAB),[15] 4-dodecylbenzenesulfonic acid (DBSA),[16] and (NH4)2HPO4.[17]
Occasionally, these reactions can be performed under microwave[18–20] and
ultrasound irradiations[21] or using an electrocatalytic system.[22,23] None of these
methods completely meet the requirements, and they all suffer from severe
disadvantages, such as long reaction times, poor yields, use of harmful volatile
organic solvents, and nonreusability of catalysts. Thus, there is a need to develop
an efficient and environmentally benign method to construct these high-value
heterocyclic compounds.
The use of lithium bromide as a mild catalyst to promote various organic trans-
formations is well documented in the literature.[24–32] In particular, lithium bromide
has been found to efficiently catalyze Cannizzaro, Tishchenko, and Meerwein–
Ponndorf–Verley reactions[33] as well as the three-component coupling of aldehydes,
amines, and trimethylsilyl for the synthesis of a-amino nitriles.[34] However, there are
no examples of the use of lithium bromide as catalyst for the synthesis of 4H-
chromene derivatives in water. In continuation of our ongoing research program
on the development of new regents=methods,[35] herein we report a facile, extremely
rapid, and high-yielding procedure for the synthesis of tetrahydro-4H-chromene
derivatives by a one-pot, three-component reaction of aryl aldehydes, active methyl-
ene compounds, and 1,3-cyclohexanedins using a catalytic amount of lithium
bromide in aqueous media (Scheme 1).
RESULTS AND DISCUSSION
The reaction was carried out by adding lithium bromide (10 mol%) to a mix-
ture of benzaldehyde, malononitrile, and dimedone in water. After the mixture
was stirred under reflux conditions for 15 min, thin-layer chromatographic (TLC)
analysis showed that the starting reactants were consumed, and the corresponding
tetrahydro-4H-chromene (4a) was formed. Using simple workup, the expected pro-
duct was isolated in 95% yield. In the absence of a catalyst, the reaction was rather
sluggish and resulted in poor yield (57%) along with benzylidenemalononitrile (18%),
even after a long reaction time (30 min) under the same conditions,[4] thus confirming
the effectiveness of LiBr as a catalyst for this reaction. The effect of various lithium
salts such as LiCl, LiClO4, and LiBF4 for this transformation were screened. Of these
lithium salts, LiBr was found to be superior in terms of yields (Table 1).
To realize the generality and versatility of the catalyst, a variety of electronically
divergent aromatic aldehydes, dimedone, and malononitrile were examined, and the
results are summarized in Table 2. In general, the aromatic aldehydes carrying either

TETRAHYDRO-4H-CHROMENE DERIVATIVES
589
Table 1. Effect of different lithium salts for the synthesis of 2-amino-7,7-dimethyl-5-
oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4a)
Entry
Catalyst
Time (min)
Yield (%)a
1
2
3
4
5
—
LiCl
30
15
15
15
15
57
88
69
75
95
LiClO4
LiBF4
LiBr
aIsolated yield.
an electron-withdrawing group or electron-donating group reacted successfully and
gave the products in good to excellent yields in less than 15 min. It is indeed gratifying
to note that substituents in the aromatic ring of aldehydes did not show any effect
on rate of the reaction and yield of the products. The heteroaryl aldehydes, such as
2-furaldehyde, 2-thiophenealdehyde, and 3-pyridinylaldehyde (entries j–l) reacted
very smoothly to obtain the corresponding derivatives in good yields. These com-
pounds have been reported to exhibit molluscicidal activity.[36] To further expand
Table 2. Lithium bromide–catalyzed preparation of tetrahydro-4H-chromene derivatives in aqueous
media
Mp (ꢀC)
Entry
Aldehydes
PhCHO
R
R1
Yield (%)a
Found
Reported
a
b
c
d
e
f
CN
CN
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
95
93
92
89
90
95
93
94
91
88
85
89
93
92
91
93
95
92
92
86
85
95
93
92
230–232
224–225
202–203
209–210
220–222
214–215
226–227
202–203
180–181
225–226
216–218
225–226
241–242
224–226
196–198
228–229
221–222
198–199
235–236
234–235
205–206
157–158
157–158
154–155
228–230[14]
223–225[14]
201–202[4]
4-MeC6H4CHO
4-MeOC6H4CHO
2,3,4-(MeO)3C6H2CHO
4-OHC6H4CHO
4-ClC6H4CHO
CN
CN
CN
CN
224–226[4]
215–216[4]
g
h
i
3-NO2-4-OHC6H3CHO
4-BrC6H4CHO
CN
CN
203–205[4]
179–180[14]
226–228[4]
214–215[36]
4-NO2C6H4CHO
2-Furaldehyde
CN
CN
j
k
l
2-Thiophenealdehyde
3-Pyridinylaldehyde
PhCHO
CN
CN
m
n
o
p
q
r
CN
CN
239–241[23]
223–225[23]
195–197[23]
226–229[10]
225–227[10]
198–200[10]
234–236[22]
232–233[36]
204–205[36]
155–157[14]
156–158[14]
153–155[14]
4-MeC6H4CHO
4-MeOC6H4CHO
4-ClC6H4CHO
H
CN
CN
H
H
2,4-Cl2C6H3CHO
3-NO2C6H4CHO
4-NO2C6H4CHO
2-Furaldehyde
CN
CN
H
H
s
CN
CN
H
t
H
u
v
w
x
2-Thiophenealdehyde
PhCHO
CN
H
CO2Et
CO2Et
CO2Et
Me
Me
Me
4-MeC6H4CHO
4-ClC6H4CHO
aIsolated yield.

590
W.-B. SUN ET AL.
Table 3. Comparative synthesis of compound 4a using the reported methods versus the present method
Entry
Catalyst
Conditions
Time (min)
Yield (%)
Ref.
1
2
3
4
5
6
7
8
TBAF
TEBA
H2O=reflux
H2O=90ꢀC
30
240
60
97
95
97
90
91
91
97
95
4
10
Na2SeO4
RE(PFO)3
HTMAB
DBSA
H2O-EtOH=reflux
EtOH=90ꢀC
H2O=85–90ꢀC
H2O=reflux
H2O=rt
11
12
300
180
120
120
15
15
16
(NH4)2HPO4
LiBr
17
This work
H2O=reflux
the scope of the present method, the replacement of 5,5-dimethyl-1,3-cyclohexane-
dione with 1,3-cyclohexanedione was examined. To our delight, under the same
conditions, the reactions proceeded steadily to provide the targeted tetrahydro-4H-
chromens in good yields. Similar results were found for these three-component con-
densation reactions with ethyl caynoacetate (Table 1, entries v–x). In all cases, the
reaction was remarkably clean, and no chromatographic separation was performed
because no impurities were observed.
The feasibility of reusing and recycling the catalyst was examined using
sequential reactions of benzaldehyde, malononitrile, and dimedone. In a typical reac-
tion, the catalyst was recovered by simple filtration from the reaction mixture, and
the filtrates containing the catalyst were reused for five cycles. The reactions
proceeded smoothly with yields of 90–95%. The result indicated that the catalyst
could be reused several times without significant loss of its activity.
In comparison with other catalysts such as TBAF, TEBA, Na2SeO4,
RE(PFO)3, HTMAB, and DBSA, which were recently reported in the formation
of tetrahydro-4H-chromenes, lithium bromide (employed here) shows equal or more
efficient catalytic activity in terms of reaction times and yields of the obtained
products (Table 3).
In summary, we have developed a general and highly efficient method for the
synthesis of tetrahydro-4H-chromene derivatives via lithium bromide–catalyzed,
one-pot, three-component reaction of aryl aldehydes, active methylene compounds,
and 1,3-cyclohexanedins in aqueous medium. The attractive features of this process
are mild reaction conditions, reusability of catalyst, short reaction times, easy
isolation of products, operational simplicity, and excellent yields, which make it
a valid contribution to the existing processes in the field of chromene derivative
synthesis.
EXPERIMENTAL
Melting points were recorded on an X-4 apparatus and are uncorrected. Infra-
red(IR) spectra were obtained using Shimadzu FTIR-8900 spectrometer using KBr
optics. 1H NMR spectra were recorded with a Varain Mercury Plus 400 spec-
trometer using tetramethylsilane (TMS) as internal standard. Mass spectra (MS)
were performed on a ThermoFinnigan LCQ Advantage instrument with an electro-
spray ionization (ESI) source (4.5 keV). Elemental analyses were performed on Vario
EL III CHNOS elemental analyzer.

TETRAHYDRO-4H-CHROMENE DERIVATIVES
591
General Procedure for the Preparation of Tetrahydro-4H-chromene
Derivatives
Lithium bromide (0.2 mmol) was added to a mixture of aldehyde (2 mmol),
active methylene (2 mmol), cyclic 1,3-dicarbonyl compound (2 mmol), and water
(5 mL), and the mixture was stirred under reflux condition for 15 min. After
completion of the reaction as indicated by TLC, the mixture was cooled to room
temperature, and the generated solid was filtered off and recrystallized from 95%
ethanol to give pure products 4.
Spectral Data for Selected Compounds
2-Amino-7,7-dimethyl-5-oxo-4-(2,3,4-trimethoxyphenyl)-5,6,7,8-tetrahydro-
4H-chromene-3-carbonitrile (4d). Mp 209–210ꢀC; IR (KBr): 3413, 3301, 3174,
2954, 2185, 1658, 1637, 1600, 1494, 1460, 1400, 1369, 1280, 1089, 1001, 790 cmꢁ1
;
1H NMR (400 MHz, DMSO-d6) d: 1.06 (s, 3H), 1.11 (s, 3H), 2.21 (AB q, J¼ 16.4 Hz,
2H), 2.44 (s, 2H), 3.82 (s, 3H), 3.84 (s, 3H), 3.96 (s, 3H), 4.53 (s, 2H), 4.60 (s,
1H), 6.58 (d, J ¼ 8.4 Hz, 1H), 6.81 (d, J ¼ 8.4 Hz, 1H) ppm; MS (ESI) m=z: 385
(M þ 1)þ. Anal. calcd. for C21H24N2O5: C, 65.61; H, 6.29; N, 7.29. Found: C,
65.42; H, 6.15; N, 7.50.
2-Amino-4-(4-hydroxy-3-nitrophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-
4H-chromene-3-carbonitrile (4g). Mp 226–227ꢀC; IR (KBr): 3400, 3330, 3193,
2960, 2200, 1685, 1664, 1608, 1533, 1400, 1373, 1247, 1211, 1161, 1035, 854 cmꢁ1
;
1H NMR (400 MHz, DMSO-d6) d: 0.94 (s, 3H), 1.02 (s, 3H), 2.17 (AB q, J¼ 16.0 Hz,
2H), 2.49 (s, 2H), 4.22 (s, 1H), 7.07 (d, J ¼ 8.8 Hz, 1H), 7.08 (s, 2H), 7.35 (dd,
J ¼ 2.4, 8.8 Hz, 1H), 7.61 (d, J ¼ 2.4 Hz, 1H), 10.86 (br s, 1H) ppm; MS (ESI)
m=z: 356 (M þ 1)þ. Anal. calcd. for C18H17N3O5: C, 60.84; H, 4.82; N, 11.83.
Found: C, 61.02; H, 4.68; N, 12.02.
2-Amino-7,7-dimethyl-5-oxo-4-thiophen-2-yl-5,6,7,8-tetrahydro-4H-
chromene-3-carbonitrile (4k). Mp 216–218ꢀC; IR (KBr): 3384, 3132, 2964, 2198,
1
1676, 1662, 1637, 1400, 1384, 1215, 1110, 1004, 854 cmꢁ1; H NMR (400 MHz,
DMSO-d6) d: 0.97 (s, 3H), 1.04 (s, 3H), 2.27 (AB q, J ¼ 16.0 Hz, 2H), 2.49 (AB q,
J ¼ 17.6 Hz, 2H), 4.53 (s, 1H), 6.85 (d, J ¼ 3.2 Hz, 1H), 6.90 (dd, J ¼ 3.2, 5.2 Hz,
1H), 7.11 (s, 2H), 7.31 (d, J ¼ 5.2 Hz, 1H) ppm; MS (ESI) m=z: 301 (M þ 1)þ; Anal.
calcd. for C16H16N2O2S: C, 63.98; H, 5.37; N, 9.33. Found: C, 64.12; H, 5.26;
N, 9.55.
2-Amino-7,7-dimethyl-5-oxo-4-pyridin-3-yl-5,6,7,8-tetrahydro-4H-chromene-
3-carbonitrile (4l). Mp 225–226ꢀC; IR (KBr): 3411, 3365, 3118, 2970, 2192, 1678,
1664, 1612, 1589, 1431, 1400, 1367, 1215, 1132, 1004, 839 cmꢁ1; 1H NMR (400 MHz,
DMSO-d6) d: 0.94 (s, 3H), 1.03 (s, 3H), 2.17 (AB q, J ¼ 16.0 Hz, 2H), 2.48–2.49
(m, 2H), 4.23 (s, 1H), 7.10 (s, 2H), 7.31 (dd, J ¼ 4.8, 7.6 Hz, 1H), 7.52 (dd, J ¼ 2.0,
7.6 Hz, 1H), 8.38 (dd, J ¼ 2.0, 4.8 Hz, 1H) ppm; MS (ESI) m=z: 296 (M þ 1)þ. Anal.
calcd. for C17H17N3O2: C, 69.14; H, 5.80; N, 14.23. Found: C, 68.98; H, 5.65;
N, 14.40.

592
W.-B. SUN ET AL.
2-Amino-4-(2,4-dichlorophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-
3-carbonitrile (4q). Mp 221–222ꢀC; IR (KBr): 3365, 3319, 3159, 2189, 1683, 1647,
1
1616, 1469, 1400, 1369, 1384, 1213, 1172, 1002, 862 cmꢁ1; H NMR (400 MHz,
DMSO-d6) d: 1.84–1.86 (m, 2H), 2.07–2.16 (m, 2H), 2.61–2.66 (m, 2H), 4.67
(s, 1H), 7.06 (s, 2H), 7.22 (d, J ¼ 8.4 Hz, 1H), 7.32 (dd, J ¼ 2.4, 8.4 Hz, 1H), 7.50
(d, J ¼ 2.4 Hz, 1H) ppm; MS (ESI) m=z: 335 (M þ 1)þ. Anal. calcd. for
C16H12Cl2N2O2: C, 57.33; H, 3.61; N, 8.36. Found: C, 57.18; H, 3.47; N, 8.58.
2-Amino-4-furan-2-yl-5-oxo-5,6,7,8-tetrahydro-4h-chromene-3-carboni-
trile (4t). Mp 234–235ꢀC; IR (KBr): 3400, 3327, 3213, 2974, 2187, 1678, 1652, 1602,
1400, 1384, 1361, 1211, 1011, 783 cmꢁ1; 1H NMR (400 MHz, DMSO-d6) d: 1.96–2.01
(m, 2H), 2.23 (t, J ¼ 6.0 Hz, 2H), 2.59 (t, J ¼ 6.0 Hz, 2H), 4.23 (s, 1H), 6.06 (d,
J ¼ 2.4 Hz, 1H), 6.22 (t, J ¼ 2.4 Hz, 1H), 7.08 (s, 2H), 7.48 (d, J ¼ 2.4 Hz, 1H)
ppm; MS (ESI) m=z: 257 (M þ 1)þ. Anal. calcd. for C14H12N2O3: C, 65.62; H,
4.72; N, 10.93. Found: C, 65.48; H, 4.56; N, 11.05.
ACKNOWLEDGMENTS
We are grateful for financial support from the National Natural Science
Foundation of China (20872025), Natural Science Foundation of Hebei Province
(B2008000149), Natural Science Foundation of Hebei Education Department
(2006318), and Research Foundation for the Doctoral Program of Hebei Normal
University (L20061314).
REFERENCES
1. Zhang, X.; Amer, A.; Fan, X.; Balzarini, J.; Neyts, J.; De Clercq, E.; Prichard, M.;
Kern, E.; Torrence, P. F. Synthesis and antiviral activities of new acyclic and
‘‘double-headed’’ nucleoside analogues. Bioorg. Chem. 2007, 35, 221–232.
2. Luo, C.; Xie, P.; Marmorstein, R. Identification of BRAF inhibitors through in silico
screening. J. Med. Chem. 2008, 51, 6121–6127.
3. Fan, X.; Zhang, X.; Zhou, L.; Keith, K. A.; Prichard, M. N.; Kern, E. R.; Torrence, P. F.
Toward orthopoxvirus countermeasures: A novel heteromorphic nucleoside of unusual
structure. J. Med. Chem. 2006, 49, 4052–4054.
4. Gao, S.; Tsai, C. H.; Tseng, C.; Yao, C.-F. Fluoride ion–catalyzed multicomponent
reactions for efficient synthesis of 4H-chromene and N-arylquinoline derivatives in
aqueous media. Tetrahedron 2008, 64, 9143–9149.
´
´
´
´
5. Marco-Contelles, J.; Leon, R.; de los Rıos, C.; Garcıa, A. G.; Lopez, M. G.; Villarroya,
M. New multipotent tetracyclic tacrines with neuroprotective activity. Bioorg. Med. Chem.
2006, 14, 8176–8185.
6. Torrence, P. F.; Fan, X.; Zhang, X.; Loiseau, P. M. Structurally diverse 5-substituted
pyrimidine nucleosides as inhibitors of leishmania donovani promastigotes in vitro.
Bioorg. Med. Chem. Lett. 2006, 16, 5047–5051.
7. Bhosale, R. S.; Magar, C. V.; Solanke, K. S.; Mane, S. B.; Choudhary, S. S.; Pawar, R. P.
Molecular iodine: An efficient catalyst for the synthesis of tetrahydrobenzo[b]pyrans.
Synth. Commun. 2007, 37, 4353–4357.
8. Wang, X.-S.; Shi, D.-Q.; Tu, S.-J.; Yao, C.-S. A convenient synthesis of 5-oxo-5,6,7,8-
tetrahydro-4 h-benzo-[b]-pyran derivatives catalyzed by KF-alumina. Synth. Commun.
2003, 33, 119–126.

TETRAHYDRO-4H-CHROMENE DERIVATIVES
593
9. Balalaie, S.; Sheikh-Ahmadi, M.; Bararjanian, M. Tetra-methyl ammonium hydroxide:
An efficient and versatile catalyst for the one-pot synthesis of tetrahydrobenzo[b]pyran
derivatives in aqueous media. Catal. Commun. 2007, 8, 1724–1728.
10. Shi, D.; Mou, J.; Zhuang, Q.; Wang, X. One-pot synthesis of 2-amino-4-aryl-
5-oxo-5,6,7,8-tetrahydro-4H-1-benzopyran-3-carbonitriles in aqueous media. J. Chem.
Res. 2004, 821–823.
11. Hekmatshoar, R.; Majedi, S.; Bakhtiari, K. Sodium selenate–catalyzed simple and efficient
synthesis of tetrahydrobenzo[b]pyran derivatives. Catal. Commun. 2008, 9, 307–310.
12. Wang, L.-M.; Shao, J.-H.; Tian, H.; Wang, Y.-H.; Liu, B. Rare-earth perfluorooctanoate
[RE(PFO)3] catalysed one-pot synthesis of benzopyran derivatives. J. Fluorine Chem.
2006, 127, 97–100.
13. Guo, S.-B.; Wang, S.-X; Li, J.-T. D,L-Proline-catalyzed one-pot synthesis of pyrans and
pyrano[2,3-c]pyrazole derivatives by a grinding method under solvent-free conditions.
Synth. Commun. 2007, 37, 2111–2120.
14. Balalaie, S.; Bararjanian, M.; Amani, A. M.; Movassagh, B. (S)-Proline as a neutral and
efficient catalyst for the one-pot synthesis of tetrahydrobenzo[b]pyran derivatives in
aqueous media. Synlett 2006, 263–266.
15. Jin, T.-S.; Wang, A.-Q.; Wang, X.; Zhang, J.-S.; Li, T.-S. A clean one-pot synthesis of
tetrahydrobenzo[b]pyran derivatives catalyzed by hexadecyltrimethyl ammonium bromide
in aqueous media. Synlett 2004, 871–873.
16. Jin, T.-S.; Wang, A.-Q.; Zhang, J.-S.; Zhang, F.-S.; Li, T.-S. One-pot synthesis of
2-amino-3-cyano-4-aryl-7,7-dimethyl-5-oxo-4H-5,6,7,8-tetrahydrobenzo[b]pyran in aqueous
medium. Chin. J. Org. Chem. 2004, 24, 1598–1600.
17. Balalaie, S.; Bararjanian, M.; Sheikh-Ahmadi, M.; Hekmat, S.; Salehi, P. Diammonium
hydrogen phosphate: An efficient and versatile catalyst for the one-pot synthesis of tetra-
hydrobenzo[b]pyran derivatives in aqueous media. Synth. Commun. 2007, 37, 1097–1108.
18. Devi, I.; Bhuyan, P. J. Sodium bromide–catalysed one-pot synthesis of tetrahydroben-
zo[b]pyrans via a three-component cyclocondensation under microwave irradiation and
solvent-free conditions. Tetrahedron Lett. 2004, 45, 8625–8627.
19. El-Rahman, N. M. A.; El-Kateb, A. A.; Mady, M. F. Simplified approach to the uncata-
lyzed Knoevenagel condensation and Michael addition reactions in water using micro-
wave irradiation. Synth. Commun. 2007, 37, 3961–3970.
20. Tu, S.-J.; Jiang, H.; Zhuang, Q.-Y.; Miao, C.-B.; Shi, D.-Q.; Wang, X.-S.; Gao, Y.
One-pot synthesis of 2-amimo-3-cyano-4-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-
benzo[b]pyran under ultrasonic irradiation without catalyst. Chin. J. Org. Chem. 2003,
23, 488–490.
21. Li, J.-T.; Xu, W.-Z.; Yang, L.-C.; Li, T.-S. One-pot synthesis of 2-amino-4-aryl-
3-carbalkoxy-7,7-dimethyl-5,6,7,8-tetrahydrobenzo[b]pyran derivatives catalyzed by KF=
basic Al2O3 under ultrasound irradiation. Synth. Commun. 2004, 34, 4565–4571.
22. Fotouhi, L.; Heravi, M. M.; Fatehi, A.; Bakhtiari, K. Electrogenerated base-promoted
synthesis of tetrahydrobenzo[b]pyran derivatives. Tetrahedron Lett. 2007, 48, 5379–5381.
23. Elinson, M. N.; Dorofeev, A. S.; Feducovich, S. K.; Gorbunov, S. V.; Nasybullin, R. F.;
Miloserdov, F. M.; Nikishin, G. I. The implication of electrocatalysis in MCR strategy:
Electrocatalytic multicomponent transformation of cyclic 1,3-diketones, aldehydes, and
malononitrile into substituted 5,6,7,8-tetrahydro-4H-chromenes. Eur. J. Org. Chem.
2006, 4335–4339.
24. Rudrawar, S. Lithium bromide: A versatile reagent in organic synthesis. Synlett 2005,
1197–1198.
25. Aroua, L.; Baklouti, A. Synthesis of a,--bis(oxazolidinone)polyoxyethylene via a lithium
bromide–catalyzed reaction of oligoethylene glycol diglycidyl ethers with isocyanates.
Synth. Commun. 2007, 37, 1935–1941.

594
W.-B. SUN ET AL.
26. Chakraborti, A. K.; Rudrawar, S.; Kondaskar, A. Lithium bromide, an inexpensive and
efficient catalyst for opening of epoxide rings by amines at room temperature under
solvent-free condition. Eur. J. Org. Chem. 2004, 3597–3600.
27. Shao, L.-X.; Shi, M. N-Bromosuccinimide and lithium bromide: An efficient combination
for the dibromination of carbon–carbon unsaturated bonds. Synlett 2005, 2639–2640.
28. Itoh, A.; Hashimoto, S.; Masaki, Y. Facile aerobic photooxidation of alcohols in the
presence of catalytic lithium bromide. Synlett 2006, 1269–1271.
´
29. Fayol, A.; Gonzalez-Zamora, E.; Bois-Choussy, M.; Zhu, J. Lithium bromide–promoted
three-component synthesis of oxa-bridged tetracyclic tetrahydroisoquinolines. Hetero-
cycles 2007, 73, 729–742.
30. Shao, Q.; Shi, W.; Li, C. Sequential reaction of glyoxal hydrates with a-bromo ketones:
Synthesis of 2,4,5-triacyl-1,3-dioxolanes. Synthesis 2008, 3925–3930.
31. Baruah, P. P.; Gadhwal, S.; Prajapati, D.; Sandhu, J. S. The Biginelli condensation: A
novel and efficient regioselective synthesis of dihydropyrimidin-2(1H)-ones using lithium
bromide. Chem. Lett. 2002, 31, 1038–1039.
32. Prajapati, D.; Lekhok, K. C.; Sandhu, J. S.; Ghosh, A. C. Lithium bromide as a new
catalyst for carbon–carbon bond formation in the solid state. J. Chem. Soc., Perkin Trans.
1 1996, 959–960.
33. Mojtahedi, M. M.; Akbarzadeh, E.; Sharifi, R.; Abaee, M. S. Lithium bromide as a
flexible, mild, and recyclable reagent for solvent-free Cannizzaro, Tishchenko, and
Meerwein–Ponndorf–Verley reactions. Org. Lett. 2007, 9, 2791–2793.
34. Suresh, A. S.; Sandhu, J. S. LiBr: A mild Lewis acid catalyst for efficient one-pot synthesis
of a-amino nitriles. Synth. Commun. 2008, 38, 3655–3661.
35. (a) Zhang, Z.-H.; Yang, S.-T.; Lin, J. Mild and efficient procedure for the synthesis of
1,5-benzodiazepines catalyzed by magnesium perchlorate. Synth. Commun. 2006, 36,
1645–1654; (b) Zhang, Z.-H.; Lin, J. Efficient and convenient method for the synthesis
of symmetrical triindolylmethanes catalyzed by iodine. Synth. Commun. 2007, 37,
209–215; (c) Zhang, P.; Yu, Y.-D.; Zhang, Z.-H. 2,4,6-Trichloro-1,3,5-triazine as an
efficient catalyst for synthesis of benzopyran derivatives under solvent-free conditions.
Synth. Commun. 2008, 38, 4474–4479; (d) Liu, Y.-H.; Zhang, Z.-H.; Li, T.-S. Efficient
conversion of epoxides into b-hydroperoxy alcohols catalyzed by antimony trichloride=
SiO2. Synthesis 2008, 3314–3318; (e) Liu, Y.-H.; Liu, Q.-S.; Zhang, Z.-H. Amberlyst-15
as a new and reusable catalyst for regioselective ring-opening reactions of epoxides to
b-alkoxy alcohols. J. Mol. Catal. A. Chem. 2008, 296, 42–46; (f) Liu, Y.-H.; Liu, Q.-S.;
Zhang, Z.-H. An efficient Friedel–Crafts alkylation of nitrogen heterocycles catalyzed
by antimony trichloride=montmorillonite K-10. Tetrahedron Lett. 2009, 50, 916–921;
(g) Mo, L.-P.; Ma, Z.-C.; Zhang, Z.-H. CuBr2-catalyzed synthesis of bis(indolyl)
methanes. Synth. Commun. 2005, 35, 1997–2004.
36. Abdelrazeka, F. M.; Metza, P.; Farrag, E. K. Synthesis and molluscicidal activity of
5-oxo-5,6,7,8-tetrahydro-4h-chromene derivatives. Arch. Pharm. Pharm. Med. Chem.
2004, 337, 482–485.