A one-pot synthesis of 1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-ones catalyzed by iron(III) phosphate under solvent-free condition

Article abstract of DOI:10.1080/15533174.2016.1216452

An efficient green route for the preparation of naphthoxazinones, applying a three-component one-pot condensation reaction of 2-naphthol, aromatic aldehyde, and urea in the presence of iron(III) phosphate under solvent-free conditions, has been developed.

Full text of DOI:10.1080/15533174.2016.1216452

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A one-pot synthesis of 1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxazine -3-ones catalyzed by
iron(III) phosphate under solvent free condition
Parisa Rahmani, Farahnaz K. Behbahani*
Department of Chemistry, Karaj Branch, Islamic Azad University, Karaj, Iran
(*Corresponding author. E-mail: Farahnazkargar@yahoo.com, Tel: +98 026 34418145, Fax: 026
34418156)
Abstract
An efficient green route for the preparation of naphthoxazinones, applying a three-component
one-pot condensation reaction of 2-naphthol, aromatic aldehyde and urea in the presence of
iron(III) phosphate under solvent free conditions has been developed. The present procedure of-
fers several advantages such as short reaction time, simple workup, recovery and reusability of
the catalyst. Also some new compounds were synthesized and procedure could easily be scaled
up.
Keywords
naphthoxazine-3-one, solvent free, iron(III) phosphate, synthesis, catalyst
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Introduction
FePO4 is cheap, safe and available reagent [1] that has been employed for the selective oxidation
of CH4 to CH3OH [2], benzene to phenol, [3] one-pot synthesis of dihydropyrimidinones and thi-
ones,[4] one-pot three component synthesis of 2, 4, 5-trisubstituted imidazoles, [5] synthesis of
1,2,4,5-tetraarylated imidazoles, [6] synthesis of polyhydroquinoline derivatives, [7] Fe(III) cata-
lyzed cycloaddition reaction of in situ formed imines with cyclic enol ethers, [8] synthesis of
1,2-disubstituted benzimidazoles [9] and synthesis of disubstituted benzimidazoles. [10]
Also many of heterocyclic systems exhibit biological activities such as naphthalene-condensed
1,3-oxazin-3-ones have been reported to act as antibacterial agents. [11] From the 1950s to the
1960s, many benzoxazines and naphthoxazines were synthesized by Burke and co-workers. [12]
Fulop et al. reported the condensation of amino alkylnaphthols with phosgene in the presence of
triethylamine to give naphthalene-condensed 1,3-oxazin-2-one derivatives in moderate yields. [13]
There are some protocols for the synthesis of naphthalene-condensed oxazinone derivatives
which are reported in the literature. [14] Recently, some of naphthalene-condensed
1,3-oxazin-3-ones have been synthesized in the presence of triethylamine. [15] In this communica-
tions, we herein report synthesis of 1,2-dihydro-1-arylnaphtho [1,2-e] [1,3]oxazine-3-ones using
aromatic aldehyde, urea and 2-naphthol in the present of iron(III) phosphate as a benign catalyst
(Scheme 1)
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Experimental
Mps were measured by using the capillary tube method with an electro thermal 9200 apparatus.
IR spectra were recorded on Perkin Elmer FT-IR spectrometer did scanning between 4000–400
cm-1. 1H NMR and 13C NMR spectra were obtained on Bruker DRX 300MHZ NMR instrument.
Chemicals shifts are reported in parts per million (S) relative to tetramethylsilane (S 0.0) as in-
ternal standard. Elemental analyses were measured by Vario EL ΙΙΙ apparatus. Analytical TLC of
all reactions was performed on Merck precoated plates (silica gel 60F-254 on aluminium). All
starting materials purchased from Merck Co.
General procedure for the synthesis of 1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-one
derivatives: A mixture of aromatic aldehyde (1 mmol), 2-naphthol (1mmol) and urea (1.5 mmol)
in the presence of FePO4 (20 mol%) was heated at 150 °C. After completion of the reaction fol-
lowed by TLC, hot ethanol was added and the catalyst was filtrated off. The organic layer con-
taining the crude product was cooled to crystallize product. The pure product was identified via
spectra instruments. Also the catalyst was recovered and reused for third times.
1,2-Dihydro-1-phenylnaphtho[1,2-e][1,3]oxazin-3-one (entry 1): This compound was ob-
tained in 95 % yield as a white solid; time = 120 min; m.p = 216-218 οC [16]; FTIR (KBr, cm-1)
υ: 3401, 1730, 1224, 1048; 1H NMR (300 MHz, DMSO-d6): δ 8.22 (1H, br, NH), 7.79 (2H, d,
J = 8.4 Hz, Ar), 7.55 (1H, d, J = 9.0 Hz, Ar), 7.34-7.20 (8H, m, Ar), 5.99 (1H, s, CH); 13C NMR
(300 MHz, DMSO-d6): δ 149.2, 147.1, 141.7, 130.0, 129.4, 128.6, 128.2, 127.9, 127.4, 126.5,
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126.4, 124.2, 122.0, 116.2, 112.7, 54.3; Anal. Calcd. for C18H13NO2 (275.09): C, 78.53; H, 4.76;
N, 5.09. Found: C, C, 78.52; H, 4.75; N, 5.10
1-(4-Chlorophenyl)-1,2-dihydronaphtho[1,2-e][1,3]oxazin-3-one (entry 2): This compound
was obtained in 95 % yield as a white solid; time = 100 min; m.p =
206-210 οC [17]; FTIR (KBr, cm-1) υ: 3228, 1736, 1223, 1013,746; 1H NMR (300 MHz,
DMSO-d6): δ 8.73 (1H, d, J = 2.1 Hz), 7.85 (2H, dd, J = 9.6, 10.2 Hz), 7.61 (1H, d, J = 7.8 Hz),
7.42-7.26 (7H, m), 6.09 (1H, d, J = 2.4 Hz); 13C NMR (300 MHz, DMSO-d6): δ 149.1, 147.4,
141.0, 132.9, 130.3, 130.1, 128.7, 128.6, 128.5, 128.4, 127.1, 124.7, 122.5, 116.5, 112.9, 53.4;
Anal. Calcd. for C18H12ClNO2 (309.06): C, 69.80; H, 3.90; N, 4.52. Found: C, 69.81; H, 3.87;
N, 4.49.
1-(2-Chlorophenyl)-1,2-dihydronaphtho [1,2-e][1,3] oxazin-3-one (entry 3): This compound
ο
was obtained in 80 % yield as white solid; time = 90 min;
m.p = 202-206 C [17]; FTIR
(KBr, cm-1) υ: 3241, 1726,
1224, 1036, 744; 1H NMR (300 MHz, DMSO-d6): δ 8.89 (sbr, 1H, NH), 7.18-8.01 (m, 10H,
Ar), 6.50 (d, 1H, J = 2.94, CH),; 13C NMR (300 MHz, DMSO-d6): δ 149.08, 147.15, 143.25,
133.09, 130.37, 130.24, 130.13, 129.76, 129.32, 129.17, 128.06, 126.32, 125.68, 124.23, 123.58,
117.43, 114.13, 52.46; Anal. Calcd. for C18H12ClNO2 (309.06): C, 69.80; H, 3.90; N, 4.52.
Found: C, 69.78; H, 3.85; N, 4.48.
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1,2-Dihydro-1-p-tolylnaphtho[1,2-e][1,3]oxazin-3-one (entry 4): This compound was obtained
in 75 % yield as a cream solid; time = 180 min; m.p =150-153 οC [19]; FTIR (KBr, cm-1) υ: 3247,
1731, 1222, 1176; 1H NMR (300 MHz, CDCl3): δ 8.03 (1H, s, NH), 7.78-7.74 (2H, m, Ar), 7.53
(1H, m, Ar), 7.36-7.31 (2H, m, Ar), 7.23 (1H, d, J = 9.0 Hz, Ar), 7.12 (2H, d, J = 8.1 Hz, Ar),
7.02 (2H, d, J = 8.1 Hz, Ar), 5.94 (1H, d, J = 3.0 Hz, CH), 2.20 (3H, s, CH3); 13C NMR (300
MHz, CDCl3): δ 149.8, 147.3, 138.6, 138.4, 130.8, 130.3, 129.8, 129.1, 128.6, 127.2, 126.6,
124.9, 122.6, 116.9, 112.4, 55.8, 20.9; Anal. Calcd. for C19H15NO2 (289.11): C, 78.87; H, 5.23; N,
4.84. Found: C, 78.82; H, 5.19; N, 4.80.
1-(4-Methoxyphenyl)-1,2-dihydronaphtho[1,2-e][1,3]oxazin-3-one (entry 5): This compound
was obtained in 85 % yield as a white solid; time = 140 min; m.p = 206-208 οC [18]; FTIR
(KBr, cm-1) υ: 3338, 1732, 1221, 1023; 1H NMR (300 MHz, CDCl3): δ 7.82 (2H, d, J = 8.7
Hz), 7.56-7.53 (1H, m), 7.39-7.36 (2H, m), 7.30 (1H, d, J = 9.0 Hz, CDCl3), 7.17 (2H, d, J = 8.1
Hz, Ar), 6.81 (2H, d, J = 8.1 Hz, Ar), 6.17 (1H, s, NH, Ar), 6.01 (1H, s, CH), 3.72 (3H, s, OCH3);
13C NMR (300 MHz, CDCl3): δ 162.3, 159.8, 147.6, 134.1, 131.0, 130.5, 129.4, 128.8, 128.2,
127.4, 125.1, 122.9, 117.2, 114.7, 112.8, 55.7, 55.3. Anal. Calcd. for C19H15NO3 (305.11): C,
74.74; H, 4.95; N, 4.59. Found: C, 74.65; H, 4.91; N, 4.55.
1-(4-(dimethylamino)phenyl)-1,2-dihydronaphtho[1,2-e][1,3]oxazin-3-one (entry 6): This
compound was obtained in 90% yield as a pale yellow solid; time = 120 min; m.p = 223-224 οC
[16]; FTIR (KBr, cm-1) υ: 3417, 1735, 1218, 1112; 1H NMR (300 MHz, CDCl3): δ 8.68 (1H,
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s, NH), 7.95 (1H, m, Ar) , 7.78 (1H, d, J = 8.67 Hz, Ar), 7.45 (2H, m, Ar), 7.35 (2H, d, J =
8.87 Hz Ar-H), 7.08 (2H, d, J = 8.07 Hz, Ar), 6.62 (2H, d, J = 8.06
Hz, Ar), 6.02 (1H, s, CH), 2.80 (6H, s, CH3); 13C NMR (300 MHz, CDCl3): δ 150.44, 149.97,
147.69, 130.86, 130.80, 130.32, 129.01, 128.09, 127.65, 126.44, 125.41, 123.10, 117.27, 115.13,
112.82, 53.88, 40.9. Anal. Calcd. for C20H18N2O2 (318.14): C, 75.45; H, 5.70; N, 8.80. Found:
C, 75.38; H, 5.66; N, 8.78.
1-(3-nitrophenyl)-1,2-dihydronaphtho[1,2-e][1,3]oxazin-3-one. (entry 7): This compound
was obtained in 75% yield as a pale yellow solid; time = 240 min; m.p = 106-110 οC [15]; FTIR
(KBr, cm-1) υ: 3380,1 722, 1527, 1348, 1222, 1176, 1096; 1H NMR (300 MHz, CDCl3): δ 8.0
(1H, d, J = 8.7 Hz, Ar), 7.95 (1H, s, Ar), 7.12-7.65 (8H, m, Ar), 6.7 (1H, s, NH), 6.15 (1H, s,
CH); 13C NMR (300 MHz, CDCl3): δ 155.53, 149.32, 147.8, 143.04, 134.4, 133.86, 130.42,
128.02, 126.07, 123.4, 123.1, 122.91, 118.6, 118.05, 115.80, 50.71. Anal. Calcd. for C18H12N2O4
(320.08): C, 67.50; H, 3.78; N, 8.75. Found: C, 67.45; H, 3.71; N, 8.67.
1-(2,4-Dichlorophenyl)-1,2-dihydronaphtho[1,2-e][1,3]oxazin-3-one. (entry 8): This com-
pound was obtained in 95% yield as a brown solid; time = 180 min; m.p = 214-216 οC[new];
FTIR (KBr, cm-1) υ : 3458, 1737, 1216, 1102, 743; 1H NMR (300 MHz, CDCl3): δ 6.84-7.09
(9H, m, Ar), 6.52 (1H, s, NH), 6.11 (1H, s, CH); 13C NMR (300 MHz, CDCl3): δ 156.5, 150.32,
147.47, 140.03, 133.96, 135.0, 131.42, 131.72, 130.33, 128,75, 127.39, 126.56, 123.30, 122.91,
118.05,115.8, 50.7. Anal. Calcd. for C18H11Cl2NO2 (343.02): C, 62.81; H, 3.22; N, 4.07. Found:
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C, 62.34; H, 3.21; N, 4.05.
1-(4-Isopropylphenyl)-1,2-dihydronaphtho[1,2-e][1,3]oxazin-3-one. (entry 9): This com-
pound was obtained in 90% yield as a pale yellow solid; time = 120 min; m.p =
230-235οC[new]; FTIR (KBr, cm-1) υ: 3265, 1730, 1289, 1223, 1109; 1H NMR (300 MHz,
CDCl3): δ 7.12-7.85 (10H, m, Ar), 6.52 (1H, s, NH), 6.02 (1H, s, CH), 2.84 (1H, sep, CH),
1.19 (6H, d, J = 3 Hz, CH3×2); 13C NMR (300 MHz, CDCl3): δ 150.53, 149.32, 147.47, 139.03,
132.96, 129.72, 129.33, 128,75, 126.89, 126.13, 122.91, 117.05, 112.80, 55.71, 33.73, 23.80.
Anal. Calcd. for C21H19NO2 (317.14): C, 79.47; H, 6.03; N, 4.41. Found: C, 79.42; H, 6.01; N,
4.37.
1-(3,4-dimethoxyphenyl)-1,2-dihydronaphtho[1,2-e][1,3]oxazin-3-one. (entry 10): This
compound was obtained in 85% yield yellow solid; time = 140 min; m.p = 188-190 οC [new];
FTIR (KBr, cm-1) υ: 3148, 1735, 1222, 1025; 1H NMR (300 MHz, CDCl3): δ 6.74-7.09 (9H,
m, Ar), 6.42 (1H, s, NH), 6.01 (1H, s, CH), 3.80 (3H, s, OMe), 3.75 (3H, s, OMe); 13C NMR
(300 MHz, CDCl3): δ 150.53, 149.32, 147.47, 139.03, 130.96, 129.72, 128,75, 127.39, 126.89,
126.56, 126.13, 122.91, 122.58, 118.05, 115.8, 56.2, 49.7. Anal. Calcd. for C20H17NO4
(335.12): C, 71.63; H, 5.11; N, 4.18. Found: C, 71.57; H, 5.09; N, 4.17.
Results and discussion
To study the condensation reaction using the catalytic amount of iron(III) phosphate (5, 10, 15
and 20 mol %), we examined the reaction times involving benzaldehyde (1 mmol), 2-naphthol (1
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mmol) and urea (1.5 mmol) under solvent free conditions as a model reaction. The best results
were obtained at 20 mol% of the catalyst to give 1-phenyl-1,2- dihydronaph-
tho[1,2-e][1,3]oxazin-3-one in 95% yield. In the absence of the catalyst, desired product was not
obtained. Therefore, the catalyst played a crucial role in the success of the reaction in terms of
time and the yields. Also, solvents such as ethanol, methanol, chloroform, water and acetonitrile
do not proceed reaction to give desired product except acetonitrile in low yield under model re-
action condition. Also, different temperatures such as 100, 120, and 150 °C were evaluated. It
was found that amidoalkyl naphthol was resulted in >150 °C. It seems, cyclization reaction needs
high temperature. To examine the generality of the process, several experimental trials illustrat-
ing this method for the synthesis of 1,2-dihydro-1-arylnaphtho [1,2-e][1,3] oxazine-3-one deriva-
tives were conducted. The results are summarized in experimental section. Benzaldehyde and
other aromatic aldehydes containing electron-withdrawing groups or electron-donating groups
were employed which were found to react well to give the corresponding
1,2-dihydro-1-arylnaphtho [1,2-e][1,3] oxazine-3-ones in good yields.
Mechanistically, the initial condensation of aromatic aldehyde with urea in the presence of
FePO4 following by dehydration leads to the formation of benzylideneurea. The nucleophilic
addition of the 2-naphthol to benzylideneurea followed by intramolecular cyclization of the re-
sulting species produce the 1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-one (Scheme 2).
To show the fairly advantages of using FePO4 in the synthesis of
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1-phenyl-1,2-dihydronaphtho[1,2-e][1,3]
oxazin-3-one, our protocol was compared with previously reported methods (Table 1). The re-
sults given in Table 1 show the advantages of this work and are evident regarding the yields of
the reactions which are very important in chemical industry especially when it is combined by
easy separation, solvent free condition and reusability of the catalyst.
Conclusion
In summary, we have described a highly efficient one-pot synthesis for the preparation of naph-
thoxazine-3-one derivatives in three-component cyclocondensation reaction of 2-naphtol, aro-
matic aldehydes and urea under solvent-free thermal conditions. Easy work-up, low cost, ready
availability of the catalyst make the procedure an attractive alternative to the existing methods
for the synthesis of naphthoxazine-3-one derivatives. This procedure could easily be scaled up
for industrial scopes.
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References
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Table 1. 1-phenyl-1,2-dihydronaphtho[1,2-e][1,3]oxazin-3-one
En-
try
1
Catalyst
Conditions
Yield
(%)
85
Ref.
FeCl3/SiO2NPs
HClO4/SiO2
Solvent free:
150 °C
16
2
Solvent free:
150 °C
88
17
3
4
5
RuCl2(PPh3)3
H3Mo12O40P
H14[NaP5W30O110]/
SiO2
Toluene: reflux 93
18
15
19
DMF: 100 °C
EtOH: reflux
87
90
6
FePO4
Solvent free:
150 °C
95
This
work
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O
O
H
R
H
H2N
NH2
N
O
R
+
FePO4
neat
O
OH
150 °C
R = H, 2-Cl, 4-Cl, 4-Me, 4-MeO, 4-(Me)2N, 3-NO2,
2,4-(Cl)2, 4-(CH3)2CH, 3,4-(OMe)2
Scheme 1 Synthesis of 1-phenyl-1,2-dihydronaphtho [1,2-e][1,3]oxazin-3-one using
FePO4 under solvent free condition
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FePO4
O
O
OH
O
O
H2N
NH2
H
N
NH2
N
NH2
H
-H2O
R
R
R
HO
FePO4
H
N
R
O
R
H
O
N
H
NH2
-NH3
Heat
O
O
Scheme 2 Purposed mechanism for the synthesis of
1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-one
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