Clean, one-pot synthesis of naphthopyran derivatives in aqueous media

Article abstract of DOI:10.1080/00397910600632096

A general and practical one-pot synthesis of naphthopyran derivatives using hexadecyltrimethylammonium bromide (HTMAB) as catalyst (10 mol%) is described. This method provides several advantages such as neutral conditions, high yields and simple workup pr

Full text of DOI:10.1080/00397910600632096

This article was downloaded by: [Dicle University]
On: 04 November 2014, At: 23:24
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
Clean, One‐Pot Synthesis of Naphthopyran
Derivatives in Aqueous Media
Tong‐Shou Jin a , Jian‐She Zhang a , Li‐Bin Liu a , Ai‐Qing Wang a &
Tong‐Shuang Li a
a Department of Chemistry , College of Chemistry and Environmental
Science, Hebei University , Baoding, China
Published online: 20 Aug 2006.
To cite this article: Tong‐Shou Jin , Jian‐She Zhang , Li‐Bin Liu , Ai‐Qing Wang & Tong‐Shuang Li (2006)
Clean, One‐Pot Synthesis of Naphthopyran Derivatives in Aqueous Media, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:14, 2009-2015, DOI:
10.1080/00397910600632096
To link to this article: http://dx.doi.org/10.1080/00397910600632096
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”)
contained in the publications on our platform. However, Taylor & Francis, our agents, and our
licensors make no representations or warranties whatsoever as to the accuracy, completeness, or
suitability for any purpose of the Content. Any opinions and views expressed in this publication
are the opinions and views of the authors, and are not the views of or endorsed by Taylor &
Francis. The accuracy of the Content should not be relied upon and should be independently
verified with primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities
whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

Synthetic Communicationsw, 36: 2009–2015, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600632096
Clean, One-Pot Synthesis of Naphthopyran
Derivatives in Aqueous Media
Tong-Shou Jin, Jian-She Zhang, Li-Bin Liu, Ai-Qing Wang,
and Tong-Shuang Li
Department of Chemistry, College of Chemistry and Environmental
Science, Hebei University, Baoding, China
Abstract: A general and practical one-pot synthesis of naphthopyran derivatives using
hexadecyltrimethylammonium bromide (HTMAB) as catalyst (10 mol%) is described.
This method provides several advantages such as neutral conditions, high yields and
simple workup procedure. The catalyst is low cost, facile, active, environmentally
friendly, and reusable. In addition, water is chosen as a green solvent.
Keywords: Aqueous media, hexadecyltrimethylammonium bromide, naphthopyran,
synthesis
INTRODUCTION
Most chemical reactions of organic substances conducted in the laboratory as
well as in industry need organic solvents as reaction media, although water is
safe, benign, environmentally friendly, and cheap compared with organic
solvents. Around 1980, Breslow et al. discovered that the Diels–Alder
reaction performed in water can be subject to huge accelerations.[1] The obser-
vation led to increased interest from synthetic organic chemists in organic
reactions in water. Soon it was discovered that other organic reactions, such
as the Claisen rearrangement,[2] the aldol condensation,[3] Diels–Alder
Received in Japan November 2, 2005
Address correspondence to Tong-Shou Jin, Department of Chemistry, College of
Chemistry and Environmental Science, Hebei University, No. 88 Hezuo Road,
Baoding 071002, China. E-mail: orgsyn@mail.hbu.edu.cn
2009

2010
T.-S. Jin et al.
reaction,[4] the benzoin condensation,[5] Mannich reaction,[6] and Michael
reaction[7] exhibit rate enhancements in water. To date, many more organic
transformations have been carried out in water.[8]
Naphthopyrans are polyfunctionalized benzopyran derivatives. Recently,
benzopyran derivatives have attracted strong interest because of their useful
biological and pharmacological activities, such as anticoagulant, spasmolytic,
diuretic, anticancer, and antianaphylactin activities.[9] Some of them can
also be employed as cosmetics and pigments[10] and utilized as potential
biodegradable agrochemicals.[11] In addition, polysubstitued benzopyran
constitutes a structural unit of a series of versatile synthesis.[12] Several
conventional synthesis of these polyfunctionalized benzopynans begins with
natural products[13] and involves the condensation of malononitrile with an
aldehyde and an activated phenol using base or amide as catalysts.[14] Each
of these methods has its own merit, but some of these methods are plagued
by poor yields, difficult workup, and effluent pollution.
In this work, we report the synthesis of naphthopyran derivatives
catalyzed by hexadecyltrimethylammonium bromide (HTMAB) in the
aqueous media. This method provides several advantages such as neutral
conditions, high yield, and simple workup procedure (Scheme 1).
To study the generality of this process, several examples illustrating this
method for the synthesis of naphthopyran derivatives were studied. The results
are summarized in Table 1. The effect of electrons and the nature of substitu-
ents on the aromatic ring did not show obvious effects in terms of yields under
this reaction condition. The reaction proceeded smoothly under refluxing
water to give the corresponding products 4 in high yields. Benzaldehyde
and other aromatic aldehydes containing electron-withdrawing groups (such
as nitro group, halide) or electron-donating groups (such as hydroxy group,
alkoxyl group) were employed and reacted well to give the corresponding
naphthopyran derivatives in good to excellent yields.
Scheme 1.

Table 1. Synthesis of naphthopyran derivatives 4 catalyzed by HTMAB in aqueous media
Mp (8C)
Time
(h)
Yielda
(%)
Entry
Ar
X
Phenol
Found
Reported
1
2
C6H5 1a
2-ClC6H4 1b
CN
CN
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
2-Naphthol
2-Naphthol
2-Naphthol
2-Naphthol
2-Naphthol
2-Naphthol
4
4
93
95
95
93
91
94
95
92
89
92
82
81
85
78
69
68
214–216
244–246
228–230
235–236
222–224
210–211
240–241
184–185
240–242
255–257
210–211
265–267
258–260
194–196
190–192
195–197
3
3-ClC6H4 1c
4-ClC6H4 1d
CN
CN
4
231–232.5[14e]
232[14b]
4
4
5
2,4-Cl2C6H3 1e
3-NO2C6H4 1f
4-NO2C6H4 1 g
4-CH3OC6H4 1 h
3,4-OCH2OC6H3 1i
4-OHC6H4 1j
CN
CN
4
6
4
214.5–216[14c]
239–241[14e]
182[14d]
7
CN
CN
4
8
4
9
CN
CN
4
10
11
12
13
14
15
16
4
252[14b]
4-ClC6H4 1 k
2-ClC6H4 1l
CN
CN
6
208[14b]
6
261–263[14b]
3,4-OCH2OC6H3 1 m
4-CH3OC6H4 1n
4-ClC6H4 1o
CN
CN
6
6
192[14d]
CO2Et
CO2Et
12
12
2,4-Cl2C6H3 1p
aIsolated yields based on aromatic aldehyde.

2012
T.-S. Jin et al.
The reaction of acromatic aldehyde with malononitrile or ethyl cyanoace-
tate and 1-naphthol or 2-naphthol gave different experimental results. From
Table 1 we know that malononitrile gives better results and needs shorter
reaction time than ethyl cyanoacetate. For instance, 4-chlorobenzaldehyde
(1k) reacted with malononitrile or ethyl cyanoacetate and 2-naphthol in the
refluxing water and gave yields of 4k (82%) and 4o (69%) in 6 or 12 h, respect-
ively. And the yield of the reaction of acromatic aldehyde with malononitrile
and 1-naphthol was much better than that of 2-naphthol. For instance, 4-chlor-
obenzaldehyde (1d) and 2-chlorobenzaldehyde (1b) were treated with malo-
nonitrile and 1-naphthol; in 4 h, they gave the isolated yields of the
corresponding compounds 4d (93%) and 4b (95%). When 4-chlorobenzalde-
hyde (1k) and 2-chlorobenzaldehyde (1l) were treated with malononitrile and
2-naphthol for 6 h, the yields of 4k (82%) and 4l (81%) were only obtained.
We conclude that malononitrile and 1-naphthol exhibit higher reactivity
than ethyl cyanoacetate and 2-naphthol.
The catalyst plays a crucial role in the success of the reaction in terms of
the rate and the yields. For example, 4-chlorobenzaldehyde reacted with mal-
ononitrile (ethyl cyanoacetate) and 1-naphthol in the presence of 1 mol%
HTMAB to give the product 4b in modest yield (55%) in refluxing water
after 4 h of reaction time. Increasing the catalyst to 5, 10, and 15 mol%
results in accelerating the reaction yields to 86%, 93%, and 93% respectively.
Use of just 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. Thus, 10 mol% HTMAB was chosen as a quantitative
catalyst for these reactions.
The catalyst could be reused six times for the synthesis of 4b without
significant 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
1
in water and those products were characterized by melting point, IR, H
NMR, and elemental analyses.
In conclusion, we have described a general and highly efficient procedure
for the preparation of naphthopyran derivatives catalyzed by HTMAB under
refluxing water. In addition, it is possible to apply the tenets of green
Table 2. Reuse of the catalyst
for syntheses of 4b
Entry
Yield (%)
1
2
3
4
5
6
95
94
93
91
90
89

One-Pot Synthesis of Naphthopyran Derivatives
2013
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, opera-
tional simplicity, cleaner reactions, and minimal environmental impact, which
make it a useful and attractive process for the synthesis of these compounds.
EXPERIMENTAL
The new compounds prepared were characterized by 1H NMR, IR, and
element analyses and are described in this section. Liquid aldehydes were
purified by distillation before use. IR spectra were recorded on a Bio-rad
1
FIS-40 spectrometer (KBr). H NMR spectra were measured on an Avance-
400 spectrometer using TMS as internal standard and CDCl3 as solvent.
Elemental analysis measured on a Heraeus (CHN, Rapid) analyzer.
General Procedure for Synthesis of Naphthopyran Derivatives
in Aqueous Media
A mixture of an aromatic aldehyde (1.0 mmol) with 1-naphthol (2- naphthol)
(1.0 mmol), malononitrile (ethyl cyanoacetate) (1.0 mmol), and HTMAB
(10 mol%) in water (20 mL) was stirred at reflux for a period of time summar-
ized in Table 1. The progress of the reaction was monitored by TLC. After
completion of the reactions, the mixture was cooled to room temperature,
solid was filtered off and washed with H2O (40 mL), and the crude products
were obtained. The crude products were purified by recrystallization from
ethanol (95%).
Data of Some Compounds
4a. IR (KBr) n (cm21) 3456, 3320, 3018, 2932, 2205, 1662, 1572, 1450, 1372,
1267, 1100, 811, 744; 1H NMR d (ppm) 4.90 (s, 1H, H-4), 7.10 (s, 2H, NH2),
7.07–7.12 (m, 6H, H-5, and ArH), 7.56–7.66 (m, 3H, H-6, 7,8), 7.94 (d, 1H,
J ¼ 8.4, H-9 or H-10), 8.23 (d, 1H, J ¼ 8.4, H-10 or H-9). Anal. calcd. for
C20H14N2O: C, 80.54; H, 4.70; N, 9.39. Found: C, 80.42; H, 4.78; N, 9.35.
4b. IR (KBr) n (cm21) 3475, 3318, 2917, 2195, 1670, 1600, 1410, 1360, 1275,
1180, 1040, 805, 750; 1H NMR d (ppm) 5.41 (s, 1H, CH), 7.20 (s, 2H, NH2),
7.01 (d, 1H, J ¼ 8.4, H-5), 7.25–7.31 (m, 3H, ArH), 7.45 (d, 1H, J ¼ 8.4,
ArH), 7.56–7.67 (m, 3H, H-6, 7, 8), 7.89 (d, 1H, J ¼ 8.4, H-9 or H-10),
8.24 (d, 1H, J ¼ 8.4, H-10 or H-9). Anal. Calcd. for C20H13ClN2O: C,
72.18; H, 3.91; N, 8.42. Found: C, 72.10; H, 4.02; N, 8.35.
4c. IR (KBr) n (cm21) 3459, 3343, 3025, 2935, 2210, 1650, 1600, 1580,
1470, 1378, 1030, 750, 700; 1H NMR d (ppm) 4.98 (s, 1H, H-4), 7.24

2014
T.-S. Jin et al.
(s, 2H, NH2), 7.12–7.38 (m, 4H, ArH), 7.23 (s, 1H, ArH-20), 7.56–7.66
(m, 3H, H-6, 7, 8), 7.89 (d, 1H, J ¼ 8.4, H-9 or H-10), 8.26 (d, 1H, J ¼ 8.4,
H-10 or H-9). Anal. calcd. for C20H13ClN2O: C, 72.18; H, 3.91; N, 8.42.
Found: C, 72.09; H, 4.05; N, 8.44.
4e. IR (KBr) n (cm21) 3459, 3333, 3035, 2186, 1663, 1600, 1575, 1466, 1378,
1200, 1050, 860, 755; 1H NMR d (ppm) 5.47 (s, 1H, H-4), 7.30 (s, 2H, NH2),
6.98 (d, 1H, J ¼ 8.4, ArH-60), 7.60 (s, 1H, ArH-30), 7.39–7.59 (m, 2H, H-5
and ArH-50), 7.69–7.89 (m, 3H, H-6, 7, 8), 8.03 (d, 1H, J ¼ 8.4, H-9 or
H-10), 8.25 (d, 1H, J ¼ 8.4, H-10 or H-9). Anal. calcd. for C20H12Cl2N2O:
C, 65.39; H, 3.27; N, 7.63. Found: C, 65.26; H, 3.23; N, 7.61.
4g. IR (KBr) n (cm21) 3460, 3335, 2196, 1665, 1600, 1575, 1536, 1500, 1346,
1270, 1195, 1100, 770; 1H NMR d (ppm) 5.12 (s, 1H, H-4), 7.29 (s, 2H, NH2),
7.05 (d, 1H, J ¼ 8.4, H-5), 7.51–7.72 (m, 3H, H-6, 7, 8), 7.52 (d, 2H, ArH-20,
60), 7.90 (d, 1H, J ¼ 8.4, H-9 or H-10), 8.15 (d, 2H, ArH-30, 50), 8.27 (d, 1H,
J ¼ 8.4, H-10 or H-9). Anal. calcd. for C20H13N3O3: C, 69.97; H, 3.79; N,
12.24. Found: C, 70.05; H, 3.92; N, 12.16.
4i. IR (KBr) n (cm21) 3438, 3324, 2907, 2196, 1673, 1605, 1575, 1490, 1405,
1
1380, 1190, 1040, 770; H NMR d (ppm) 4.88 (s, 1H, H-4), 5.92 (s, 2H,
OCH2O), 6.74–6.85 (m, 3H, ArH), 7.13 (s, 2H, NH2), 7.55–7.65 (m, 3H,
H-6, 7, 8), 7.88 (d, 1H, J ¼ 8.4, H-9 or H-10), 8.22 (d, 1H, J ¼ 8.4, H-10
or H-9). Anal. calcd. for C21H14N2O3: C, 73.68; H, 4.09; N, 8.19. Found: C,
73.74; H, 4.03; N, 8.26.
4m. IR (KBr) n (cm21) 3443, 3340, 3045, 2886, 2195, 1657, 1600, 1580,
1
1500, 1400, 1234, 1040, 743; H NMR d (ppm) 5.25 (s, 1H, H-4), 5.91
(s, 2H, -OCH2O-), 6.95(s, 2H, NH2), 6.66–6.80 (m, 3H, ArH), 7.86–7.95
(m, 2H, H-5 or H-8), 7.91 (d, 1H, J ¼ 8.0, H-9 or H-10), 7.20–7.49
(m, 3H, H-6, 7, 10). Anal. calcd. for C21H14N2O3: C, 73.68; H, 4.09; N,
8.19. Found: C, 73.75; H, 3.97; N, 8.08.
4o. IR (KBr) n (cm21) 3475, 3325, 1675, 1630, 1505, 1460, 1400, 1305, 1215,
1070, 825; 1H NMR d (ppm) 1.26 (t, J ¼ 7.2 Hz, 3H, CH3), 4.09
(q, J ¼ 7.2 Hz, 2H, OCH2), 5.51 (s, 1H, CH), 7.23–7.53 (m, 7H, Naph-H),
7.65 (s, 2H, NH2), 7.92 (d, J ¼ 8 Hz, 2H, ArH), 7.99 (d, J ¼ 8 Hz, 1H,
ArH). Anal. calcd. for C22H18ClNO3: C, 69.57; H, 4.78; N, 3.69. Found: C,
69.48; H, 4.74; N, 3.82.
4p. IR (KBr) n (cm21) 3395, 3290, 1610, 1525, 1465, 1395, 1370, 1310, 1257,
1100, 1075, 1030, 745; 1H NMR d (ppm) 1.19 (t, J ¼ 7.2 Hz, 3H, CH3), 4.07
(q, J ¼ 7.2 Hz, 2H, OCH2), 5.81 (s, 2H, NH2), 7.23–7.53 (m, 7H, Naph-H),
7.92 (d, J ¼ 8.8 Hz, 2H, ArH), 8.14 (d, J ¼ 8.8 Hz, 1H, ArH). Anal. calcd.
for C22H17Cl2NO3: C, 63.78; H, 4.14; N, 3.38. Found: C, 63.90; H, 4.09; N,
3.29.

One-Pot Synthesis of Naphthopyran Derivatives
ACKNOWLEDGMENTS
2015
This project was supported by the National Natural Science Foundation of
China (29872011), Educational Ministry of China, Educational Department
of Hebei Province (990104), and Science and Technology Commission of
Hebei Province.
REFERENCES
1. (a) Rideout, D. C.; Breslow, R. J. Am. Chem. Soc. 1980, 102, 7817;
(b) Breslow, R.; Maitra, U.; Rideout, D. Tetrahedron Lett. 1983, 24, 1901;
(c) Eggelte, T. A.; Koning, H. D.; Huisman, H. O. Tetrahedron 1973, 29, 2491.
2. (a) Gajewski, J. J.; Jurayj, J.; Kimbrough, D. R.; Grande, M. E.; Ganem, B.;
Carpenter, B. K. J. Am. Chem. Soc. 1987, 109, 1170; (b) Grieco, P. A.;
Brandes, E. B.; Mccann, S.; Clark, J. D. J. Org. Chem. 1989, 54, 5849;
(c) Severance, D. L.; Jorgensen, W. L. J. Am. Chem. Soc. 1992, 114, 10966;
(d) Gao, J. J. Am. Chem. Soc. 1994, 116, 1563; (e) Gajewski, J. J.;
Brichford, N. L. J. Am. Chem. Soc. 1994, 116, 3165.
3. (a) Lubineau, A. J. Org. Chem. 1986, 51, 2142; (b) Lubineau, A.; Meyer, E. Tetra-
hedron 1988, 44, 6065; (c) Tian, H. Y.; Chen, Y. J.; Wang, D.; Li, C.
J. Tetrahedron Lett. 2000, 41, 2529.
4. (a) Meijer, A.; Otto, S.; Engberts, J. B. F. N. J. Org. Chem. 1998, 63, 8989;
(b) Otto, S.; Engberts, J. B. F. N.; Kwak, J. C. T. J. Am. Chem. Soc. 1998, 120,
9517; (c) Yu, L. B.; Li, J.; Ramirez, J. D.; Chen, P.; Wang, P. G. J. Org. Chem.
1997, 62, 903; (d) Zhu, Z. L.; Espenson, J. H. J. Am. Chem. Soc. 1997, 119, 3507.
5. Kool, E. T.; Breslow, R. J. Am. Chem. Soc. 1988, 110, 1596.
6. Manabe, K.; Mori, Y.; Kobayashi, S. Tetrahedron 2001, 57, 2537.
7. (a) Mori, Y.; Kakumoto, K.; Manabe, K.; Kobayashi, S. Tetrahedron Lett. 2000,
41, 3107; (b) Keller, E.; Feringa, B. L. Tetrahedron Lett. 1996, 37, 1879.
8. (a) Grieco, P. A. Organic Synthesis in Water; Blacky: London, 1998; (b) Li, C. J.;
Chan, T. H. Organic Reactions in Aqueous Media; Wiley: New York, 1997;
(c) Jin, T. S.; Zhang, J. S.; Xiao, J. C.; Wang, A. Q.; Li, T. S. Synlett 2004, 866;
(d) Jin, T. S.; Wang, A. Q.; Wang, X. J.; Zhang, S.; Li, T. S. Synlett 2004, 871.
9. (a) Andreani, L. L.; Lapi, E. Boll. Chim. Farm. 1960, 99, 583; (b) Bonsignore, L.;
Loy, G.; Secci, D.; Calignano, A. Eur. J. Med. Chem. 1993, 28, 517.
10. Ellis, G. P.; Weissberger, A.; Taylor, E. C. The chemistry of heterocyclic
compounds. In Chromenes, Chromanes and Chromeones; Wiley: New York,
1977; p. 13.
11. Hafez, E. A. A.; Elnagdi, M. H.; Elagamey, A. G. A.; Ei-Taweel, F. M. A. A.
Heterocycles 1987, 26, 903.
12. (a) Hatakeyama, S.; Ochi, N.; Numata, H.; Takano, S. J. Chem. Soc. Chem.
Commun. 1988, 1202; (b) Cingolant, G. M.; Pigini, M. J. Med. Chem. 1969, 12, 531.
13. Callaghan, C. N. O.; Murry, T. B. H. J. Chem. Res. 1995, 21.
14. (a) Abdel-Larif, F. F. Indian J. Chem. 1990, 29B, 664; (b) Elagamey, A. G.; El-
Taweel, F. M. A. Indian J. Chem. 1990, 29B, 885; (c) Bioxham, J.; Dell, C. P.;
Smith, C. W. Heterocycles 1994, 38, 399; (d) Elagamey, A. G. A.;
Sawllim, S. Z.; El-Taweel, F. M. A.; Elnagdi, M. H. Collect. Czech. Chem.
Commun. 1988, 53, 1534; (e) Ballini, R.; Bosica, G.; Conforti, M. L.;
Maggi, R.; Mazzacani, A.; Righi, P.; Sartori, G. Tetrahedron 2001, 57, 1395.