An efficient one-pot three component synthesis of 1,2-dihydro-1- arylnaphtho[1,2-e][1,3]oxazine-3-ones using montmorillonite K10 under solvent free conditions

Article abstract of DOI:10.1002/jhet.312

(Chemical Equation Presented) An efficient green protocol for the preparation of 1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-ones employing a three-component one-pot condensation reaction of b-naphthol, aromatic aldehyde, urea or thiourea in the presen

Full text of DOI:10.1002/jhet.312

March 2010
An Efficient One-Pot Three Component Synthesis of
1,2-Dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-ones Using
Montmorillonite K10 under Solvent Free Conditions
313
Srinivas Kantevari,* Srinivasu V. N. Vuppalapati, Rajashaker Bantu, and
Lingaiah Nagarapu
Organic Chemistry Division-II, Indian Institute of Chemical Technology, Hyderabad 500007, India
*E-mail: kantevari@yahoo.com
Received September 29, 2009
DOI 10.1002/jhet.312
Published online 2 March 2010 in Wiley InterScience (www.interscience.wiley.com).
An efficient green protocol for the preparation of 1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-ones
employing a three-component one-pot condensation reaction of b-naphthol, aromatic aldehyde, urea or
thiourea in the presence of montmorillonite K10 clay under solvent free conditions has been described.
The present procedure offers advantages such as shorter reaction time (<90 min), simple workup, excel-
lent yields, recovery and reusability of catalyst.
J. Heterocyclic Chem., 47, 313 (2010).
INTRODUCTION
zine-3-ones. In continuation of our work on the use of
heterogeneous solid acid catalysts [6], we describe in
this report a general and efficient green protocol for the
preparation of 1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxa-
zine-3-ones, employing a one-pot three-component con-
densation of b-naphthol, aromatic aldehydes urea or
thiourea in the presence of montmorillonite K10 clay
under solvent free conditions. This method is superior to
the reported methods in all aspects such as short reac-
tion times and excellent yields.
Recently, benzoxazinone derivatisation has attained
considerable significance in potential antiviral target
compounds [1]. The prime driving force in this area is
the fight against HIV by developing more efficacious
drugs than Efavirenz (Sustiva), a benzoxazinone deriva-
tive which is presently in clinical use for the treatment
of AIDS.
The construction of new analogs of bioactive hetero-
cyclic compounds represents a major challenge in syn-
thetic organic and medicinal chemistry. Due to their
broad spectrum of biological activities naphthalene-con-
densed 1,3-oxazin-3-ones have been reported to act as
antibacterial agents [2]. Heterogeneous organic reactions
have proven useful to chemists both in academia and in
industry. Clay-catalyzed organic transformations have
generated considerable interest because of their inexpen-
sive nature and special catalytic attributes under hetero-
geneous reaction conditions [3].
RESULTS AND DISCUSSION
Initially to determine the most appropriate reaction
conditions and to evaluate the catalytic activity of
Lewis/protic acid catalysts, a model study was carried
out on the synthesis of 1,2-dihydro-1-arylnaphtho[1,2-
e][1,3] oxazine-3-one 4a (Table 1) by the condensation
of benzaldehyde 1a with b-naphthol 2 and urea 3a in
different sets of reaction conditions. Among all the
tested catalysts such as Silica sulfuric acid, p-TSA,
AcOH, LiCl, CuCl2, HClO4-SiO2, Amberlist-15, and IR-
120 under solvent free conditions we found that the best
results were obtained with the condensation in the pres-
ence of montmorillonite K10 catalyst (Table 1, entry 1).
The condensation of mixture of benzaldehyde 1a (1
mmol) with b-naphthol 2 (1 mmol) and urea 3a (1.5
mmol) in the presence of montmorillonite K10 (0. 3
mmol) was carried out at 160ꢀC for 0.5 h under solvent
free conditions (Scheme 1). The reaction proceeded
In this context, a recent report [4] and related publica-
tions [5] on one pot three component synthesis of 1,2-
dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-ones by the
condensation of aldehydes, urea or thiourea with b-
naphthol in the presence of acid p-TSA attracted our
attention. This method suffers from the drawbacks of
green chemistry such as prolonged reaction times, re-
covery and reusability of catalyst. The demand for envi-
ronmentally benign procedure with reusable catalyst
necessitated us to develop an alternate method for the
synthesis of 1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxa-
C
V
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314
S. Kantevari, S. V. N. Vuppalapati, R. Bantu, and L. Nagarapu
Vol 47
Table 1
is believed to proceed through the formation of an N-
acylimine intermediate 5 formed in situ by the reaction
of aldehyde 1 with urea or thiourea 3. The subsequent
addition of the b-naphthol to the N-acylimine, followed
by cyclization affords the corresponding products 4(a-p)
and ammonia.
Synthesis of 1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxazine -3-one 4a
using different catalysts under solvent free conditions.
Entry
Catalyst
Yield (%)b
Ref
1
2
3
4
5
6
7
8
9
Montmorillonite K10 clay
Silica sulfuric acid
p-TSA
89
65
58
45
38
30
64
48
44
–
–
4
4
4
4
–
–
–
The simplicity, together with the use of inexpensive,
non-toxic, and environmentally benign catalyst under
solvent free condition is other remarkable features of the
procedure. The catalyst was recovered by filtration,
washed several times with methanol, dried at 120ꢀC for
72 h and reused with out significant loss of catalyst
activity.
AcOH
LiCl
CuCl2
HClO4-SiO2
Amberlist-15
IR120
a
Benzaldehyde (1 mmol), urea (1.5 mmol), b-napthol (1 mmol), cata-
lyst (0.3 mmol).
In conclusion, we have reported herein a novel and
ecofriendly method for the synthesis of 1,2-dihydro-1-
aryl naphtho[1,2-e][1,3]oxazine-3-ones using Montmoril-
lonite K10 clay under solvent free conditions. The
advantages of the present protocol are mild heterogene-
ous reaction conditions, shorter reaction times, and easy
work up. The inexpensive, ready availability, recycla-
blity of the catalyst make the procedure an attractive al-
ternative to the existing methods for the synthesis of
1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-ones.
b Isolated yields.
smoothly and gave the corresponding 1,2-dihydro-1-aryl
naphtho[1,2-e][1,3]oxazine-3-one 4a as the sole product
in 89% isolated yield. Ethyl acetate was added to the
reaction mixture and simply filtering the mixture and
evaporating the solvent from the filtrate gave the crude
product, which was purified by crystallization in ethyl
acetate: hexane (1:3) to obtain 4a as white solid.
To evaluate the generality of the process, several
examples illustrating the present method for the synthe-
sis of 1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-
ones 4 was studied (Table 2). The reaction of b-naph-
thol 2 with various aromatic aldehydes bearing electron
withdrawing groups (such as nitro, halide), electron
releasing groups (such as methoxy, methyl or hydroxyl
groups), and urea or thiourea was carried out in the
presence of Montmorillonite K 10 as a catalyst.
EXPERIMENTAL
General procedure. A mixture of b-naphthol (1 mmol),
aldehyde (1 mmol), urea or thiourea (1.5 mmol) and Montmo-
rillonite K10 clay (0.3 mmol) was rapidly stirred and heated at
160ꢀC for the specified time (Table 2). After TLC indicates
the disappearance of starting material, reaction was cooled to
room temperature, ethyl acetate (25 mL) was added and the in-
soluble material was filtered to separate the catalyst. The fil-
trate was concentrated under vacuum and the crude residue
was purified by crystallization in ethyl acetate: hexane (1:3) to
afford pure product 4 in excellent yields as specified in Table
2. The catalyst filtered was washed with methanol (3 ꢁ 10
mL), dried at 120ꢀC for 72 h and reused. The isolated product
yields after each cycle is 78%. All products obtained were
fully characterized by spectroscopic methods such as IR, 1H
NMR, 13C NMR and mass spectroscopy and have been identi-
fied by the comparison of the spectral data with those
reported.
The heterocyclic aldehydes such as furfural (entry m,
Table 2) and 2-Chloroquinoline-3-aldehyde (entry n, Ta-
ble 2) on reaction with b-naphthol 2 and urea 3 in the
presence of montmorillonite K10 clay under solvent free
conditions was sluggish and the corresponding products
were isolated only in 10–15% yields. The poor reaction
of heterocyclic aldehydes (entry m & n Table 2) with b-
naphthol 2 can be explained by considering the possibil-
ity of binding of basic hetero atom (m & n) on the sur-
face of Montmorillonite K10 clay. The results obtained
in the current method are illustrated in Table 2. All
products obtained were fully characterized by spectro-
scopic methods such as IR, 1H NMR, 13C NMR and
mass spectroscopy and also by comparison with the
reported spectral data [4].
1-Phenyl-1,2-dihydronaphtho[1,2-e][1,3]oxazin-3-one (4a). m.p.
210–212ꢀC, IR (KBr) mmax 3281, 2928, 1727, 1627, 1514,
1458, 1435, 1396, 1338, 1289, 1221, 1165, 1111, 981, 925,
828, 745 cmꢂ1
.
1H NMR (200 MHz, CDCl3 þ DMSO-d6): d
Scheme 1. X ¼ O or S 4a-p.
On the basis of all our experimental results, together
with the literature reports [4], we have proposed the
plausible mechanism for the formation of 1,2-dihydro-1-
arylnaphtho[1,2-e][1,3]oxazine-3-ones 4 in the presence
of Montmorillonite K10 clay (Scheme 2). The reaction
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DOI 10.1002/jhet

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An Efficient One-Pot Three Component Synthesis of 1,2-Dihydro-1-arylnaphtho
[1,2-e][1,3]oxazine-3-ones Using Montmorillonite K10 under Solvent Free Conditions
315
Table 2
Reaction of b-naphthol with various aldehydes and urea or thiourea.
Entry
a
Aldehyde 1
Urea/Thiourea 3
Product 4
Reaction Time (min)
30
Yielda (%)
NH2CONH2
89
b
c
d
e
f
NH2CONH2
NH2CONH2
NH2CONH2
NH2CONH2
NH2CONH2
NH2CONH2
NH2CONH2
NH2CONH2
NH2CONH2
30
55
50
30
30
45
60
45
90
84
85
90
79
85
84
75
72
70
g
h
i
j
k
NH2CONH2
90
72
(Continued)
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S. Kantevari, S. V. N. Vuppalapati, R. Bantu, and L. Nagarapu
Vol 47
Table 2
(Continued)
Entry
Aldehyde 1
Urea/Thiourea 3
Product 4
Reaction Time (min)
Yielda (%)
l
NH2CONH2
90
70
15
10
64
65
m
n
o
p
NH2CONH2
NH2CONH2
NH2CONH2
NH2CONH2
90
90
45
45
a Field of isolated products.
6.04 (d, J ¼ 3.12 Hz, 1H), 7.26–7.40 (m, 7H), 7.56–7.64 (m,
2H), 7.78–7.86 (m, 2H), 8.56 (s, 1H). 13C NMR (50 MHz,
CDCl3 þ DMSO-d6): d 56.4, 113.8, 117.6, 123.4, 125.0,
127.4, 127.8, 127.9, 129.2, 129.5, 129.9, 131.0, 131.3, 142.0,
148.1, 150.1. MS (ESI) m/z 276 ([M þ H]þ). Anal. Calcd for
C18H13NO2: C, 78.53; H, 4.76; N, 5.09. Found: C, 78.53; H,
4.75; N, 5.09.
1-(2,4-Dichlorophenyl)-1,2-dihydronaphtho[1,2-e][1,3]oxa-
zin-3-one (4d). m.p.239–242ꢀC. IR (KBr) mmax 3244, 3141,
1737, 1627, 1623, 1586, 1468, 1393, 1287, 1225, 1117, 748
1
cmꢂ1. H NMR (200 MHz, CDCl3 þ DMSO-d6): d 6.48 (d, J
¼ 3.12 Hz, 1H), 6.96–7.08 (m, 2H), 7.28–7.52 (m, 5H), 7.81–
7.89 (m, 2H) 8.29 (s, 1H). 13C NMR (50 MHz, CDCl3
þ
DMSO-d6): d 50.2, 111.0, 115.7, 121.1, 124.1, 126.6, 127.2,
127.7, 127.9, 128.4, 129.3, 129.7, 132.0, 133.3, 137.0, 147.0,
148.4. MS (ESI) m/z 344 ([M þ H]þ). Anal. Calcd for
C18H11Cl2NO2: C, 62.81; H, 3.22; N, 4.07. Found: C, 62.82;
H, 3.22; N, 4.06.
1-(4-Fluorophenyl)-1,2-dihydronaphtho[1,2-e][1,3] oxazin-
3-one (4b). m.p. 199–200ꢀC. IR (KBr) mmax 3427, 3215, 3127,
1
2955, 1750, 1627, 1509, 1396, 1224, 1180, 808, 736 cmꢂ1. H
NMR (200 MHz, CDCl3 þ DMSO-d6): d 6.02 (d, J ¼ 2.29
Hz, 1H), 6.93–7.01 (m, 2H), 7.22–7.54 (m, 6H), 7.79–7.86 (m,
2H), 8.54 (s, 1H). 13C NMR (50 MHz, CDCl3 þ DMSO-d6): d
52.9, 112.0, 114.3, 114.8, 115.7, 121.5, 123.9, 126.2, 127.5,
127.8, 127.9, 129.1, 129.5, 137.2, 146.6, 148.7, 158.4, 163.3.
MS (ESI) m/z 294 ([M þ H]þ). Anal. Calcd for C18H12FNO2:
C, 73.71; H, 4.12; N, 4.78. Found: C, 73.72; H, 4.11; N, 4.77.
1-(3-Chlorophenyl)-1,2-dihydronaphtho[1,2-e][1,3]oxazin-3-
one (4c). m.p.192–195ꢀC. IR (KBr) mmax 3433, 3348, 2923,
Scheme 2. Plausible mechanism for the formation of 1,2-dihydro-1-
arylnaphtho[1,2-e][1,3]oxazine-3-ones 4.
1752, 1678, 1623, 1464, 1384, 1222, 1177 cmꢂ1 1H NMR
.
(200 MHz, CDCl3 þ DMSO-d6): d 6.07 (d, J ¼ 2.93 Hz, 1H),
7.22–7.56 (m, 7H), 7.78–7.90 (m, 3H), 8.72 (s, 1H). 13C NMR
(50 MHz, CDCl3 þ DMSO-d6): d 52.8, 111.4, 115.4, 121.2,
123.7, 124.1, 125.7, 126.1, 126.8, 127.3, 127.6, 129.1, 132.8,
143.1, 146.4, 148.3, 154.5. MS (ESI) m/z 310 ([M þ H]þ).
Anal. Calcd for C18H12ClNO2: C, 69.80; H, 3.90; N, 4.52.
Found: C, 69.79; H, 3.91; N, 4.52.
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DOI 10.1002/jhet

March 2010
An Efficient One-Pot Three Component Synthesis of 1,2-Dihydro-1-arylnaphtho
[1,2-e][1,3]oxazine-3-ones Using Montmorillonite K10 under Solvent Free Conditions
317
742 cmꢂ1
.
1H NMR (200 MHz, CDCl3 þ DMSO-d6): d 4.45
1-(3-Nitrophenyl)-1,2-dihydronaphtho[1,2-e][1,3] oxazin-3-
one (4e). m.p. 228–230ꢀC, IR (KBr) mmax 3380, 3065, 2924,
(s, 1H), 7.02–7.86 (m, 10H), 9.10 (brs, 1H). 13C NMR (50
MHz, CDCl3 þ DMSO-d6): d 30.0, 108.7, 116.8, 117.9, 118.2,
122.4, 122.5, 124.6, 125.7, 127.2, 127.8, 128.2, 128.8, 131.6,
133.1, 134.4, 142.2, 152.5, 154.8. MS (ESI) m/z 360 ([M þ
H]þ). Anal. Calcd for C19H12F3NOS: C, 63.50; H, 3.37; N,
3.90. Found: C, 63.51; H, 3.37; N, 3.91.
1
1727, 1627, 1594, 1527, 1346, 1221, 1176, 810, 744 cmꢂ1. H
NMR (200 MHz, CDCl3 þ DMSO-d6): d 6.42 (d, J ¼ 2.34
Hz, 1H), 7.31–7.95 (m, 8H), 8.32–8.35 (m, 2H), 8.86 (s, 1H).
13C NMR (50 MHz, CDCl3 þ DMSO-d6): d 52.3, 110.9,
115.6, 120.9, 121.2, 121.7, 123.9, 126.3, 127.4, 127.6, 128.9,
129.3, 129.4, 132.0, 143.0, 146.9, 148.2. MS (ESI) m/z 321
([M þ H]þ). Anal. Calcd for C18H12N2O4: C, 67.50; H, 3.78;
N, 8.75. Found: C, 67.49; H, 3.78; N, 8.76.
1-(3-Trifluoromethylphenyl)-1,2-dihydronaphtho [1,2-e][1,3]
oxazin-3-one (4f). m.p. 251–253ꢀC, IR (KBr) mmax 3446,
3248, 2924, 1752, 1705, 1631, 1592, 1517, 1395, 1321, 1223,
1171, 1113, 1064, 920, 813, 738 cmꢂ1 1H NMR (200 MHz,
.
CDCl3 þ DMSO-d6): d 6.15 (d, J ¼ 2.93 Hz, 1H), 7.28–7.55
(m, 7H), 7.72 (s, 1H), 7.82–7.90 (m, 2H), 8.76 (s, 1H). 13C
NMR (50 MHz, CDCl3 þ DMSO-d6): d 53.0, 111.4, 115.7,
120.0, 121.3, 122.9, 123.7, 124.0, 126.4, 127.6, 127.9, 128.6,
129.5, 142.2, 146.8, 148.6. MS (ESI) m/z 344 ([M þ H]þ).
Anal. Calcd for C19H12F3NO2: C, 66.47; H, 3.52; N, 4.08.
Found: C, 66.48; H, 3.52; N, 4.08.
Acknowledgments. The authors thank Dr. J. S. Yadav, Director,
IICT, and Dr. V. V. Narayana Reddy Head, Organic Chemistry
Division-II, IICT Hyderabad, for their constant encouragement
and support.
REFERENCES AND NOTES
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1-(2-Chlorophenyl)-1,2-dihydronaphtho[1,2-e][1,3] oxazin-
3-one (4g). m.p. 222–224ꢀC, IR (KBr) mmax 3393, 3059, 2925,
1741, 1583, 1438, 1372, 1231, 1123, 1042, 976, 784, 746
1
cmꢂ1. H NMR (200 MHz, CDCl3 þ DMSO-d6): d 6.54 (d, J
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¼ 1.46 Hz, 1H), 7.12–7.52 (m, 8H), 7.83–7.88 (m, 2H), 8.10
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111.4, 115.6, 121.2, 123.9, 126.4, 126.8, 127.5, 127.9, 128.1,
128.5, 128.6, 129.3, 131.0, 138.2, 146.8, 148.4. MS (ESI) m/z
310([M þ H]þ). Anal. Calcd for C18H12ClNO2: C, 69.80; H,
3.90; N, 4.52. Found: C, 69.79; H, 3.90; N, 4.51.
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1-(4-Fluorophenyl)-1,2-dihydronaphtho[1,2-e][1,3]oxazine-
3-thione (4o). Thick syrup; IR (KBr) mmax 3060, 2923, 1628,
1600, 1508, 1460, 1390, 1267, 1216, 1162, 1016, 843, 811,
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750 cmꢂ1
.
1H NMR (200 MHz, CDCl3 þ DMSO-d6): d 4.37
(s, 1H), 6.84–7.82 (m, 10H), 9.22 (brs, 1H). 13C NMR (75
MHz, CDCl3): d 29.7, 109.4, 115.0, 115.2, 117.7, 123.1,
123.5, 126.3, 126.4, 126.6, 127.6, 128.5, 129.4, 129.5, 129.7,
151.0, 153.3. MS (ESI) m/z 360 ([M þ H]þ). Anal. Calcd for
C18H12FNOS: C, 69.88; H, 3.91; N, 4.53. Found: C, 69.88; H,
3.91; N, 4.54.
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1-(3-Trifluoromethylphenyl)-1,2-dihydronaphtho [1,2-e][1,3]
oxazine-3-thione (4p). Thick syrup; IR (KBr) mmax 3240, 3052,
2923, 1627, 1512, 1443, 1327, 1263, 1165, 1121, 1071, 845,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet