An environmentally benign one-pot synthesis of 1,2-dihydro-1-aryl-3H- naphth[1,2-e][1,3]oxazin-3-one derivatives catalysed by phosphomolybdic acid

Article abstract of DOI:10.2298/JSC100410016C

A phosphomolybdic acid catalysed novel method for the synthesis of 1,2-dihydro-1-aryl-3H-naphth[1,2-e][1,3]oxazin-3-one derivatives by a one-pot, three-component reaction of β-naphthol, aromatic aldehydes and urea in excellent yields is described.

Full text of DOI:10.2298/JSC100410016C

J. Serb. Chem. Soc. 76 (1) 21–26 (2011)
JSCS–4095
UDC 546.18–32+546.77–32+
547.867:544.4:547–316
Original scientific paper
An environmentally benign one-pot synthesis of 1,2-dihydro-1-
-aryl-3H-naphth[1,2-e][1,3]oxazin-3-one derivatives catalysed
by phosphomolybdic acid
1
1
ATUL CHASKAR1,2 , VIMAL VYAVHARE , VIKAS PADALKAR , KIRAN
*
PHATANGARE1 AND HRUSHIKESH DEOKAR1
1C. K. Thakur Research Centre, Navi Mumbai-410206, India and 2Dipartimento di chimica,
materiali ed ingegneria chimica “Giulio Natta” Politecnico di Milano, Milan, Italy
(Received 10 April, revised 29 June 2010)
Abstract: A phosphomolybdic acid catalysed novel method for the synthesis of
1,2-dihydro-1-aryl-3H-naphth[1,2-e][1,3]oxazin-3-one derivatives by a one-pot,
three-component reaction of β-naphthol, aromatic aldehydes and urea in excel-
lent yields is described.
Keywords: MCRs; phosphomolybdic acid; naphtho-oxazine; catalysis; alde-
hydes.
INTRODUCTION
Oxazinone, benzoxazinone and their derivatives are an important class of
heterocyclic compounds. These heterocyclic systems exhibit biological activities,
1
such as HIV-1 reverse transcriptase inhibitors (Fig. 1). Naphthalene-condensed
2
1,3-oxazin-2-ones have been reported to act as antibacterial agents. They have
been used as precursors in the preparation of phosphinic ligands for asymmetric
3
catalysis. Hitherto, only few reports for the synthesis of naphthalene-condensed
oxazinone derivatives have been documented in the literature. Aromatic oxazines
were first synthesized in 1944 by Holly and Cope through Mannich reactions
4
from phenols, formaldehyde, and amines. From the 1950s to the 1960s, many
5
benzoxazines and naphthoxazines were synthesized by Burke and co-workers.
Fulop et al. reported the condensation of amino alkylnaphthols as precursors with
phosgene in the presence of triethylamine giving naphthalene-condensed 1,3-
6
-oxazin-2-one derivatives in moderate yields. Cimarelli and co-workers used
7
carbonyl di-imidazole instead of phosgene for the synthesis of these compounds.
*Corresponding author. E-mail: achaskar@rediffmail.com
doi: 10.2298/JSC100410016C
21
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CHASKAR et al.
Recently, Bazgir et al. reported the synthesis of naphthoxazine derivatives using
8
p-TSA and microwave radiation under solvent-free conditions.
Fig. 1. Efavirenz (SustivaTM).
However, some difficulties still exist, such as unsatisfactory yields, long
reaction times, strong acidic conditions, highly expensive reagents. The required
solvents or the reagents used are toxic and hazardous which causes environ-
mental pollution. Therefore, to overcome these limitations, the discovery and de-
velopment of a new, simple, green, one pot and efficient protocol with a highly
active catalyst for the preparation of 1,2-dihydro-1-aryl-3H-naphth[1,2-e][1,3]-
oxazin-3-one derivatives under neutral, mild and practical conditions is of prime
interest.
In recent decades, considerable attention has been devoted to heterogeneous
organic transformations using heteropolyacids. Due to the super acidic properties
of solid heteropolyacids (HPAs), they have been employed in numerous appli-
9
cations as useful and versatile acid catalysts over the last three decades. They
are usually solids that are insoluble in non-polar solvents but highly soluble in
polar ones. They can be used in bulk or supported forms in both homogeneous
and heterogeneous systems. They are more active catalysts than conventional
10
inorganic and organic acids for various reactions in solution; phosphomolybdic
acid as a HPA catalyst has become important in industries related to fine chemi-
11
cals. Furthermore, heteropolyacids have several advantages, such as mild reac-
tion conditions, easy work-up procedures and high selectivity including high fle-
xibility in the modification of the acid strength, ease of handling, environmental
compatibility, non-toxicity and experimental simplicity. They are non-corrosive
12
and environmentally benign, as they can be reused and recycled.
Our group has been working extensively on the development of novel me-
13
thodologies under mild reaction conditions using phosphomolybdic acid. In
this study, the convenient and practical synthesis of 1,2-dihydro-1-aryl-3H-
-naphth[1,2-e][1,3]oxazin-3-one derivatives via the simple and efficient, one-pot
multi-component condensation reaction of β-naphthol, aldehydes and urea in the
presence of a catalytic amount of phosphomolybdic acid in DMF was realised
(Scheme 1). The products were synthesized in good to excellent yields and cha-
1
13
racterized by H-NMR, C-NMR and mass spectroscopy, as well as by their
physical constants. The physical and spectral data of known compounds are in
6–8
agreement with those reported in the literature.
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ONE-POT SYNTHESIS OF 1,2-DIHYDRO-1-ARYL-3H-NAPHTH[1,2-e][1,3]OXAZIN-3-ONE
23
EXPERIMENTAL
All commercial reagents were used as received without purification and all solvents were
of reagent grade. The reaction was monitored by TLC using 0.25 mm Merck silica gel 60
F254 pre-coated plates, which were visualized with UV light. The melting points were deter-
mined in open capillaries. The IR spectra were recorded on a PerkinElmer 257 spectrometer
using KBr discs. The 1H-NMR and 13C-NMR spectra were recorded on a VXR-300 MHz ins-
trument using TMS as the internal standard.
General experimental procedure
A mixture of β-naphthol (0.01 mol), aldehyde (0.01 mol), urea (0.015 mol), phospho-
molybdic acid (0.001 mol) and dimethylformamide (5 mL) was heated at 100 °C for an
appropriate time (see later). After completion of reaction, as monitored by TLC, the reaction
mixture was poured onto crushed ice, extracted with ethyl acetate and washed with water. The
ethyl acetate extract was dried over anhydrous sodium sulphate and concentrated under re-
duced pressure. The crude product was crystallized by using 2-propanol.
Scheme 1. Synthesis of 1,2-dihydro-1-aryl-3H-naphth[1,2-e][1,3]oxazin-3-ones.
RESULTS AND DISCUSSION
A preliminary experiment was performed to determine the suitable reaction
conditions. The reaction of β-naphthol, benzaldehyde and urea in presence of
phosphomolybdic acid was investigated. The best result was obtained in the pre-
sence of phosphomolybdic acid at 100 °C in DMF (Table I).
TABLE I. Effect of solvents on the preparation of 1,2-dihydro-l-phenyl-3H-naphth[1,2-e]-
[1,3]oxazin-3-one (reaction conditions: β-naphthol (0.01 mol), benzaldehyde (0.01 mol), urea
(0.015 mol), phosphomolybdic acid (0.001 mol), solvent (5 mL))
Entry
Solvent
t / °C
Time, h
Isolated yield, %
1
2
3
4
5
6
7
8
Ethanol
Methanol
Dimethylformamide
Acetonitrile
IPA
Chloroform
Toluene
Dichloromethane
75
55
100
75
100
55
110
38
6.5
6
3
7
6.5
8
72
75
87
48
70
52
48
40
7.5
10
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2011 Copyright (CC) SCS

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CHASKAR et al.
To investigate the feasibility of this synthetic methodology for the synthesis
of 1,2-dihydro-1-aryl-3H-naphth[1,2-e][1,3]oxazin-3-one derivatives, the reac-
tion of β-naphthol with a variety of aromatic aldehydes and urea in presence of a
catalytic amount of phosphomolybdic acid was performed, furnishing thereby the
respective 1,2-dihydro-1-aryl-3H-naphth[1,2-e][1,3]oxazin-3-one derivatives in
high yields. The optimized results are summarized in Table II, from which it can
be observed that the results were excellent in terms of yields and product purity
using aromatic aldehydes carrying electron-donating as well as electron-with-
drawing substituents. When the reactions were conducted without the catalyst,
the product yields were only 15–20 %, therefore phosphomolybdic acid provokes
a considerable enhancement in the conversion.
In this protocol, phosphomolybdic acid was used as a recyclable catalyst.
After completion of the reaction, the catalyst was recovered as follows: the reac-
tion mixture was poured into ice-cold water and extracted with ethyl acetate. The
ethyl acetate layer was then washed with water, dried over sodium sulphate and
evaporated under reduced pressure to obtain the product. The aqueous layer was
evaporated under reduced pressure to recover the phosphomolybdic acid, which
was further reused for two more processes. The average percentage yield of re-
covery of phosphomolybdic acid is given in Table III.
TABLE II. Synthesis of 1,2-dihydro-1-aryl-3H-naphth[1,2-e][1,3]oxazin-3-one derivatives
(reaction conditions: β-naphthol (0.01 mol), aldehyde (0.01 mol), urea (0.015 mol) phospho-
molybdic acid (0.001 mol), dimethylformamide (5 mL), t = 100 °C)
Entry
Product
Aldehyde (X)
Time, h
3
Isolated yield, %
1
2
3
4
5
6
7
4a
4b
4c
4d
4e
4f
2-OH
2-Cl
4-Cl
4-OMe
4-Me
4-NO2
3-NO2
85
89
89
86
87
92
92
2.5
4g
8
9
10
4h
4i
4k
H
3
3.5
87
85
84
2,5-OH
2-OH, 5-OMe
TABLE III. Recyclability of the system using phosphomolybdic acid for the preparation of
1,2-dihydro-1-aryl-3H-naphth[1,2-e][1,3]oxazin-3-one derivatives
Run
Yield, %
1
2
3
87
87
86
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ONE-POT SYNTHESIS OF 1,2-DIHYDRO-1-ARYL-3H-NAPHTH[1,2-e][1,3]OXAZIN-3-ONE
25
Representative spectral data
1,2-Dihydro-l-(4-chlorolphenyl)-3H-naphth[1,2-e][1,3]oxazin-3-one (4c). M.p.
–1
1
209 °C. IR (KBr, cm ): 3224, 3146, 1734, 1600, 850, 730. H-NMR (300 MHz,
DMSO-d , δ, ppm): 6.21(1H, s, CH), 7.30–8.12 (10H, m, Ar-H), 8.89 (1H, s,
6
13
NH). C-NMR (300 MHz, DMSO-d , δ, ppm): 53, 114, 117, 123, 125, 127,
6
+
128, 129, 130, 129.5, 129.6, 130.5, 133, 142, 147, 149 ppm. MS (m/z): 309 (M ).
1,2-Dihydro-l-(4-methylphenyl)-3H-naphth[1,2-e][1,3]oxazin-3-one (4e). M.p.
–1
1
167 °C. IR (KBr, cm ): 3225, 3127, 7210, 1658, 1580, 830. H-NMR (300
MHz, DMSO-d , δ, ppm): 2.23 (3H, s, CH ), 6.15 (1H, d, CH), 7.05–7.88 (10H,
6
3
13
m, Ar-H), 8.78 (1H, s, NH). C-NMR (300 MHz, DMSO-d , δ, ppm): 22, 52,
6
113, 116, 122, 126, 126, 128, 130, 129, 131, 132, 133, 137, 140, 148, 150. MS
+
(m/z): 290 (M ).
CONCLUSIONS
In conclusion, a novel method with judicious choice of the solvent and cata-
lyst for the synthesis of 1,2-dihydro-1-aryl-3H-naphth[1,2-e][1,3]oxazin-3-one
derivatives has been developed. This new protocol has enormous potential for the
preparation of a large library of 1,3-oxazin-2-ones in an expeditious and environ-
mentally friendly way in good to excellent yields from readily accessible starting
materials. A variety of functional groups are compatible with the reaction condi-
tions.
Acknowledgements. The authors are grateful to University Grand Commission, New Del-
hi and to the University of Mumbai for financial support. Thanks to Dr. S.T. Gadade, Prin-
cipal, C. K. Thakur College, for providing the laboratory and other facilities.
И З В О Д
ЕКОЛОШКИ БЕНИГНА СИНТЕЗА ДЕРИВАТА 1,2-ДИХИДРО-1-АРИЛ-3H-НАФТ-
[1,2-е][1,3]ОКСАЗИН-3-OНА, У ЈЕДНОМ РЕАКЦИОНОМ КОРАКУ,
КАТАЛИЗОВАНА ФОСФОМОЛИБДЕНСКОМ КИСЕЛИНОМ
ATUL CHASKAR1,2, VIMAL VYAVHARE1, VIKAS PADALKAR1, KIRAN PHATANGARE1 и HRUSHIKESH DEOKAR1
1C. K. Thakur Research Centre, Navi Mumbai-410206, India и 2Dipartimento di chimica, materiali ed
ingegneria chimica “Giulio Natta” Politecnico di Milano, Milan, Italy
Описан је нов поступак за синтезу 1,2-дихидро-1-арил-3H-нафт[1,2-e][1,3]оксазин-3-
-oна у једном реакционом кораку и високом приносу, реакцијом β-нафтола, ароматичних
алдехида и урее у присуству фосфомолибденске киселине као катализатора.
(Примљено 10. априла, ревидирано 29. јуна 2010)
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