Graphene oxide mediated solvent-free three component reaction for the synthesis of 1-amidoalkyl-2-naphthols and 1,2-dihydro-1-arylnaphth[1,2-e][1,3]oxazin-3-ones

Article abstract of DOI:10.1016/j.tetlet.2016.09.067

The present report describes a solvent-free synthesis of 1-amidoalkyl-2-naphthols and 1,2-dihydro-1-arylnaphth[1,2-e][1,3]oxazin-3-ones via one-pot multicomponent reaction of 2-naphthol, aryl/heteryl aldehyde, and amide/urea in presence of graphene oxide

Full text of DOI:10.1016/j.tetlet.2016.09.067

Accepted Manuscript
Graphene oxide mediated solvent-free three component reaction for the syn-
thesis of 1-amidoalkyl -2-naphthols and 1,2-dihydro-1-arylnaphth[1,2-e]
[1,3]oxazin -3-ones
Annah Gupta, Dilpreet Kour, Vivek K. Gupta, Kamal K. Kapoor
PII:
S0040-4039(16)31237-0
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.09.067
TETL 48137
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
26 August 2016
16 September 2016
19 September 2016
Please cite this article as: Gupta, A., Kour, D., Gupta, V.K., Kapoor, K.K., Graphene oxide mediated solvent-free
three component reaction for the synthesis of 1-amidoalkyl -2-naphthols and 1,2-dihydro-1-arylnaphth[1,2-e]
[1,3]oxazin -3-ones, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.09.067
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Graphical Abstract
Graphene oxide mediated solvent-free three
component reaction for the synthesis of 1-
amidoalkyl-2-naphthols and 1,2-dihydro-1-
arylnaphth[1,2-e][1,3]oxazin -3-ones
Leave this area blank for abstract info.
Annah Gupta, Dilpreet Kour, Vivek K. Gupta and Kamal K. Kapoor*
O
R
O
Ar
NH
OH
R
NH2
(R=CH3, C6H5)
H
O
Ar
N
O
OH
O
Graphene oxide
H2N NH2
Ar CHO
+
120 oC
Solvent-free
O
Ar
N
O
N
OH
H
(Total 19 examples)
 High Yield
 Broad Substrate Scope
 Eco-friendly Catalyst
 Easily Recoverable and Reusable Catalyst

1
Tetrahedron Letters
Graphene oxide mediated solvent-free three component reaction for the synthesis of
1-amidoalkyl -2-naphthols and 1,2-dihydro-1-arylnaphth[1,2-e][1,3]oxazin -3-ones
Annah Guptaa , Dilpreet Koura, Vivek K. Guptab and Kamal K. Kapoora
aDepartment of Chemistry, University of Jammu, Jammu-180 006, India
b X-ray Crystallography Group, Department of Physics & Electronics, University of Jammu, Jammu 180 006, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The present report describes a solvent-free synthesis of 1-amidoalkyl-2-naphthols and 1,2-
dihydro-1-arylnaphth[1,2-e][1,3]oxazin-3-ones via one-pot multicomponent reaction of 2-
naphthol, aryl/heteryl aldehyde and amide/urea in presence of graphene oxide as an eco- benign
heterogeneous catalyst in good to excellent yields. The catalyst is easily recoverable and
reusable.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Graphene oxide
1-amidoalkyl-2-naphthol
Naphth[1,2-e][1,3]oxazin -3-one
2-Naphthol
Amide
Urea
Heterogeneous catalysis
23
liquid [Hnmp]HSO4 etc.24 Other methods for the synthesis of
1-amidoalkyl-2-naphthols upon hydrolysis produces 1-amino
alkyl-2-naphthols, known to possess depressor and bradycardiac
effects.1 1-aminoalkyl-2-naphthols being 1,3-amino alcohol also
find applications in asymmetric synthesis and catalysis as
bidentate ligands.2 Oxazinones shows a variety of biological
activities such as antibacterial,3 HIV-1 reverse transcriptase
inhibitors,4 human cytomegalovirus protease inhibitor,5
neuropeptide Y5 antagonist.6
naphthoxazinone involve the condensation of aminoalkyl
naphthol with phosgene/TEA
25
or diimidazole/DMAP.26
However, these protocols suffer from one or more disadvantages
from the green chemistry perspective such as prolonged reaction
time, use of carcinogenic reagents and solvents, unsatisfactory
yields, strong acidic conditions and non-recyclability of the
catalyst. Therefore, it is desirable to develop clean procedures
utilizing eco-benign heterogeneous catalyst for the synthesis of 1-
amidoalkyl-2-naphthols and naphthoxazinone derivatives.
One-pot multicomponent reactions serve as a powerful tool
for the synthesis of wide variety of structurally diverse
molecules7 including pharmaceuticals owing to their high atom
economy, time and energy efficiency, high selectivity, low cost,
simpler and environmental friendly procedures. Among the
various known multicomponent reactions, the synthesis of
amidoalkyl naphthol is one of the well established reactions.
Graphene oxide (GO) has emerged as
a promising,
economical and efficient carbocatalyst27 in organic synthesis due
to its large surface area, biocompatibility, inertness, low-cost and
ease in synthesis. The acidic nature (pH 4.5 at 0.1 mg mL-1)
28
29
30
and oxidising properties
of graphene oxide result from the
presence of many oxygen containing functionalities such as
epoxy, hydroxyl and carboxyl groups on its surface (Figure 1).
In our ongoing efforts to develop newer methodologies,31 we
wished to explore the role of graphene oxide in one-pot synthesis
of 1-amidoalkyl-2-naphthols and 1,2-dihydro-1-arylnaphth[1,2-e]
[1,3]oxazin -3-ones from 2-naphthol, aldehyde and amide/urea.
1-amidoalkyl-2-naphthols and naphthoxazinone derivatives
have been synthesized by the one-pot three component reaction
of 2-naphthol, aldehyde and amide or urea in presence of
catalysts such as iodine,8 FeCl3.SiO2,9 cellulose sulphuric acid,10
p-TSA,11 sulfanilic acid- functionalized silica coated nano-Fe2O3
particles,12 montmorillonite K10,13 cyanuric chloride,14
Fe(HSO4)3,15 SnCl4. 5H2O,16 HClO4–SiO2,17 P2O5,18 zwitter ionic
salts,19
N,N,N’,N’-tetrabromobenzene-1,3-disulphonamide
[TBBDA],20 TMSCl/NaI, 21 nano- sulfated zirconia,22 acidic ionic
———
 Corresponding author Tel.: +91-191-2453969;
fax: +91-191-2450014/2431365; e-mail: kamalkka@gmail.com

2
Tetrahedron Letters
COOH
COOH
HOOC
OH
16
-
-
-
17 wt %
52 wt %
70 wt %
120
120
120
79
93
93
COOH
O
O
O
O
O
HOOC
HO
17
HO
O
COOH
COOH
18
O
O
a Isolated Yield
OH
COOH
With the optimized conditions in hand, the substrate scope of the
reaction was studied and results are depicted in Table 2.
Aldehydes bearing electron withdrawing and electron donating
groups underwent reactions smoothly. It was also observed that
COOH
Figure 1: Structural model of graphene oxide
A reaction of 2-naphthol (1mmol), anisaldehyde (1mmol) and
benzamide (1.2 mmol) in the presence of 35 wt % of graphene
the present reactions gave satisfactory results with acetamide as
oxide (which was prepared by modified Hummers method28 and
11, 21
well as 2-pyrrolidone. Akin to earlier observations,10,
usage
was characterized by IR spectrum) in
yielded the desired product N-((2-hydroxynaphthalen-1-
yl)(4-methoxyphenyl)methyl) benzamide albeit in low yield
(35%). To improve the yield of the product, ethanol was replaced
with various solvents, but only a marginal increase in yield was
noticed (Entry 1-8, Table 1). Stripping away the solvent from
refluxing ethanol
of urea led to the formation of cyclized product 1,2-dihydro-1-
arylnaphth[1,2-e][1,3]oxazin-3-one 7. When thiophene-2-
carboxaldehyde was used, the corresponding crystalline product
(7g) was obtained in 85% yield, the structure of which was
further confirmed by single crystal X-ray analysis (Figure 2). 32
o
the reaction and heating at 80 C resulted in the improvement of
yield (Entry 9, Table 1). However, further increasing the
o
temperature of the reaction revealed that at 120 C, the product
was obtained in 93% yield. (Entry 9-14, Table 1). In order to
establish the role of GO, the reaction was carried out without
catalyst, but desired product was obtained in only 35% yield
(Entry 15, Table 1). Variation in the amount of catalyst (17, 52,
70 wt %) w.r.t. one mmol of 2-naphthol didn’t lead to any
improvement (Entry 16-18, Table 1).
Table 1: Optimization of reaction conditions
CHO
H3CO
Graphene oxide
O
O
OH
NH
OH
H2N
+
+
Figure 2: Single crystal X-ray structure of compound 7g
OCH3
2
(1 mmol)
1
3
6(f)
(1 mmol)
(1.2 mmol)
Amount of
catalyst
Entry
Solvent
Temp( oC)
Yielda(%)
1
2
3
4
5
6
7
8
9
EtOH
MeOH
n-Butanol
Toluene
CH3CN
CHCl3
35 wt%
35 wt %
35 wt %
35 wt %
35 wt %
35 wt %
35 wt %
35 wt %
35 wt %
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
80
35
40
19
54
44
41
31
33
72
DCE
1,4-Dioxane
-
10
-
35 wt %
90
75
11
12
13
14
15
-
-
-
-
-
35 wt %
35 wt %
35 wt %
35 wt %
Nil
100
110
120
130
120
82
90
93
93
35

3
Table 2: Synthesis of 1-amidoalkyl-2-naphthols and 1,2-dihydro-1-arylnaphth[1,2-e][1,3] oxazin-3-ones by the reaction of 2-
naphthol, aldehyde and various amides/ urea.
O
R
O
Ar
NH
OH
R
NH2
(3)
(R=CH3, C6H5)
(6)
O
H
Ar
N
O
H2N NH2
Graphene oxide
(35 wt %)
120 oC
OH
+
O
(4)
Ar CHO
(7)
O
Solvent-free
(2)
(1)
O
N
H
Ar
N
(5)
OH
(8)
O
CH3
NH
OH
H3CO
NO2
O
CH3
NH
OH
O
CH3
NH
OH
O
CH3
NH
OH
(6a)
20 min, 90%
(6b)
15 min, 92%
(6d)
25 min, 88%
(6c)
15 min, 89%
NO2
O
H3CO
N
O
O
O
NH
OH
NH
NH
OH
NH
OH
OH
(6g)
15 min, 87%
(6h)
(6e)
20 min, 88%
(6f)
15 min, 93%
20 min, 87%
H3CO
Cl
Cl
H
H
H
N
O
N
H
O
O
O
N
O
N
O
O
O
(7b)
20 min, 89%
(7a)
25 min, 87%
(7c)
30 min, 85%
(7d)
30 min, 84%
NO2
H
O
H
N
O
N
H
S
N
O
O
N
N
O
OH
O
O
(7g)
30 min, 85%
(8a)
20 min, 89%
(7f)
25 min, 86%
(7e)
25 min, 87%
NO2
O
O
Br
O
H3CO
N
N
N
OH
OH
OH
(8d)
30 min, 85%
(8c)
25 min, 88%
(8b)
20 min, 91%
catalyst is stable and recyclable up to six runs without any
significant loss of activity.
To check the recyclability of the catalyst, GO was recovered
from the reaction of 2-naphthol, anisaldehyde and benzamide
and was reused, after washing with ethanol, in a series of six
In conclusion, GO has been found to be an efficient
heterogeneous catalyst for the one-pot synthesis of 1-
amidoalkyl-2-naphthols and 1,2-dihydro-1-arylnaphth[1,2-
e][1,3]oxazin-3-ones from 2-naphthol, aldehyde and various
amides and urea under solvent- free conditions. The present
consecutive
runs
for
the
synthesis
of
N-((2-
hydroxynaphthalen-1-yl)(4-methoxyphenyl) methyl)benzamide
and the results are depicted in Figure 3 making it evident that

4
Tetrahedron
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reduced reaction time, easy work-up and handling. The method
is environmentally safe and catalyst is recyclable.
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Compd. 2012, 48, 185–188.
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2011, 31, 1909-1913.
24. Singh, R. K.; Bala, R.; Duvedi, R.; Kumar, S. Iran. J. Catal.
2015, 5, 187-206.
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Chem. 2004, 41, 367–373.
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1314–1321.
Figure 3: Recyclability of catalyst
27. (a) Kundu, S.; Basu. B. RSC Adv. 2015, 5, 50178-50185; (b)
Navalon, S.; Dhakshinamoorthy, A.; Alvaro, M.; Garcia, H.
Chem. Rev. 2014, 114, 6179–6212; (c) Dreyer, D. R.; Todd, A.
D.; Bielawski, C. W. Chem. Soc. Rev. 2014, 43, 5288–5301; (d)
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(e )Kumar, A. V.; Rao, K. R. Tetrahedron Lett. 2011, 52, 5188-
5191.
Acknowledgement
The authors are thankful to Department of Chemistry,
University of Jammu for providing all necessary facilities and
Department of Science and Technology, Government of India,
New Delhi for NMR facility under PURSE and INSPIRE
fellowship [AG].
28. Hummers, W. S.; Offeman, R. E. J. Am. Chem. Soc. 1958, 80,
1339-1339.
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537-545.
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31. (a) Gupta, A.; Khajuria, R.; Kapoor, K. K. Synth. Commun.
2016, 46, 31-38; (b) Saini, Y.; Khajuria, R.; Rana, L. K.;
Hundal, M. S.; Gupta, V. K.; Kant, R.; Kapoor, K. K.
Tetrahedron, 2016, 72, 257-263; (c) Khajuria, R.; Kannaboina,
P.; Kapoor, K. K.; Gupta, A.; Raina, G.; Jassal, A. K.; Rana, L.
V.; Hundal, M. S.; Das, P. Org. Biomol. Chem. 2015, 13, 5944-
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32. Crystal data of product 7g: C32H22N2O4S2,
Formula weight=562.
64, Wavelength=0.71073 Å, Orthorhombic, P bca, a =7.8313
(6) Å, b =13.8840 (11) Å, c =24.667 (2) Å, α = 90°, β = 90°, =
90°, V=2682.1 (4) Å3, Z=4, DCalcd=1.393 Mg/m3, CCDC No.
1500314.
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33. General procedure for the synthesis of 1-amidoalkyl-2-
naphthols and 1,2-dihydro-1-arylnaphth[1,2-e][1,3] oxazin-
3-ones: A mixture of 2-naphthol (1mmol), aldehyde (1mmol),
amide/urea (1.2 mmol) and graphene oxide (35 wt %) was
grounded in a pestle-mortar and was transferred to 25 ml round-
bottom flask, which was heated in oil-bath maintained at 120 oC
till the completion of reaction (TLC). After cooling the
reaction, ethanol (20 ml) was added and resultant mixture was
sonicated for 10 min. The catalyst was filtered and the filtrate
upon concentration to 5 ml resulted in precipitation of the
product. The product was isolated by filtration.
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Commun. 2007, 8, 1857–1862.

5
Highlights
 This
protocol
offers
solvent-free
synthesis.
 Graphene oxide is recoverable and
reusable.
 Works well with benzamide, acetamide,
2-pyrrolidone as well as with urea.
 Rapid access to a variety of products in
good yields.