Synthesis of 2-aryl-7-methyl-4-thioxo-4H-pyrano[3,4-e][1,3]oxazin-5-one by three-component condensation

Article abstract of DOI:10.3184/174751915X14383268906316

A novel method for oxazine ring formation is established though the reaction of ammonium thiocyanate and aroyl chlorides with 4-hydroxy-6-methyl-2H-pyran-2-one in the presence of N-methylimidazole to afford 2-aryl-7-methyl-4-thioxo-4H-pyrano[3,4-e][1,3]ox

Full text of DOI:10.3184/174751915X14383268906316

492 RESEARCH PAPER
VOL. 39 AUGUST, 492–493
JOURNAL OF CHEMICAL RESEARCH 2015
Synthesis of 2-aryl-7-methyl-4-thioxo-4H-pyrano[3,4-e][1,3]oxazin-5-one by
three-component condensation
Ali Khazaeian and Alireza Hassanabadi*
Department of Chemistry, Zahedan Branch, Islamic Azad University, PO Box 98135-978, Zahedan, Iran
A novel method for oxazine ring formation is established though the reaction of ammonium thiocyanate and aroyl chlorides with 4-hydroxy-
6
-methyl-2H-pyran-2-one in the presence of N-methylimidazole to afford 2-aryl-7-methyl-4-thioxo-4H-pyrano[3,4-e][1,3]oxazin-5-one in
excellent yields.
Keywords: 4-hydroxy-6-methyl-2H-pyran-2-one, aroyl chlorides, ammonium thiocyanate, N-methylimidazole, pyrano[3,4-e][1,3]oxazines
Pyrano-1,3-oxazine derivatives have versatile applications
in the biological fields as antibacterial and cancer screening
Results and discussion
11
Using reaction conditions similar to those described previously,
an aroyl chloride 2 was reacted with ammonium thiocyanate 3
initially at room temperature and then at 90 C for 5 min prior
to the addition of 4-hydroxy-6-methyl-2H-pyran-2-one 1. After
cooling to room temperature, N-methylimidazole (10 mol%)
was added and the mixture stirred for 6 h to afford the arylated
bicyclic thionoheterocycles 4 in good yields (Scheme 1).
1-3
agents. They also have antifungal action and are used as
4
,5
o
herbicides. The thio derivatives of pyrano-1,3-benzoxazine
6
have inflammatory and antipyretic activities.
Several syntheses of pyrano[3,4-e][1,3]oxazine derivatives
7-10
11
have already been reported. Khalilzadeh et al. synthesised
a series of arylated bi- and tricyclic thioheterocycles through
the N-methylimidazole-catalysed reaction of phenol and 1- and
1
Structures of compounds 4a–f were confirmed by IR, H
13
1
2
-naphthols with a series of aroyl chlorides and ammonium
NMR, C NMR, and mass spectral data. For example, the H
NMR spectrum of 4a exhibited nine proton resonances and 12
carbon resonances, in agreement with the proposed structure.
thiocyanate. We now describe how we have used the procedure
11
of Khalilzadeh et al. to synthesise another class of arylated
bicyclic thionoheterocycle by a three-component condensation
reaction of 4-hydroxy-6-methyl-2H-pyran-2-one and aroyl
chlorides with ammonium thiocyanate in the presence of
N-methylimidazole.
13
The C=S group resonance in C NMR spectra of 4a appears at
194.85 ppm. The mass spectrum of 4a displayed the molecular
ion peak at m/z = 271. The mechanism of the reaction is
11
probably similar to that reported by Khalilzadeh et al.
N
O
O
O
N
N
H C
3
H C
O
O
+
3
O
CH3
Solvent-Free, r. t.
S
+ NH SCN
4
Ar
Cl
OH
4
1
2
3
Ar
Ar
C H
%Yield
86
*
4
a
6
5
b
c
4-ClC H4
6
90
4
-BrC H4
88
91
6
d
e
f
3
-NO C H
4
2
6
4
-NO C H
2
3
6
4
4
93
85
4-CH
C H
6
*
Isolated yields
Scheme 1
*
Correspondent. E-mail: ar_hasanabadi@yahoo.com

JOURNAL OF CHEMICAL RESEARCH 2015 493
1
In conclusion, the reaction of ammonium thiocyanate and a
series of aroyl chlorides with 4-hydroxy-6-methyl-2H-pyran-
%): 350 (5). H NMR (400 MHz, CDCl ): δ 2.13 (3H, s, CH ), 5.91 (1H,
3
3
3
3
s, =CH), 7.42 (2H, d, J = 8Hz, 2CH of C H Br), 7.76 (2H, d, J
HH 6 4 HH
8Hz, 2CH of C H Br) ppm. C NMR (100.6 MHz, CDCl ): δ 19.22
CH ), 88.05, 100.13, 122.72, 127.36, 129.15, 130.67, 132.09, 141.63,
61.86, 165.44 and 193.70 ppm.
-(3-Nitrophenyl)-7-methyl-4-thioxo-4H-pyrano[3,4-e][1,3]oxazin-
-one (4d): Yellow powder; m.p. 156–158 C, IR (KBr) (ν cm ):
716, 1669, 1564, 1347, 1285, 1090. Anal. calcd for C H N O S: C,
1
3
=
2
7
-one in the presence of N-methylimidazole afforded 2-aryl-
-methyl-4-thioxo-4H-pyrano[3,4-e][1,3]oxazin-5-one in good
yields. The present procedure has the advantage that the reaction
is performed under neutral conditions and the starting material
can be used without any activation or modification.
6
4
3
(
3
1
2
o
-1
5
max
1
14 8 2 5
Experimental
53.16; H, 2.55; N, 8.86; found: C, 53.06; H, 2.41; N, 8.95%. MS (m/z, %):
1
3
=
16 (9). H NMR (400 MHz, CDCl ): δ 2.06 (3H, s, CH ), 5.79 (1H, s,
All melting points are uncorrected. Elemental analyses were
performed using a Heraeus CHN-O-Rapid analyser. Mass spectra
were recorded on a Finnigan-MAT 8430 mass spectrometer operating
at an ionisation potential of 70 eV. IR spectra of selected compounds
were recorded on a Shimadzu IR-470 spectrometer in KBr discs. NMR
spectra were obtained on a Bruker DRX-400 Avance spectrometer
3
3
13
CH), 7.77–8.50 (4H, m, 4CH of C H NO ) ppm. C NMR (100.6 MHz,
6 4 2
CDCl ): δ 19.35 (CH ), 88.43, 100.70, 122.95, 129.37, 130.10, 130.87,
3
3
132.61, 135.27, 136.52, 149.07, 161.23, 163.22 and 194.67 ppm.
2
-(4-Nitrophenyl)-7-methyl-4-thioxo-4H-pyrano[3,4-e][1,3]oxazin-
o
-1
5
-one (4e): Yellow powder; m.p. 140–142 C, IR (KBr) (ν cm ): 1711,
max
1
13
1668, 1552, 1344, 1280, 1087. Anal. calcd for C H N O S: C, 53.16; H,
(
H NMR at 400 MHz, C NMR at 100 MHz) in CDCl using TMS
14 8 2 5
3
2
.55; N, 8.86; found: C, 53.01; H, 2.38; N, 9.02%. MS (m/z, %): 316 (5).
as internal standard. The chemicals used in this work were purchased
from Fluka (Buchs, Switzerland) and were used without further
purification.
1
H NMR (400 MHz, CDCl ): δ 2.01 (3H, s, CH ), 5.82 (1H, s, =CH), 7.97
3
3
3
3
(2 H, d, J = 8 Hz, 2 CH of C H NO ), 8.08 (2 H, d, J = 8 Hz, 2 CH
HH 6 4 2 HH
13
of C H NO ) ppm. C NMR (100.6 MHz, CDCl ): δ 19.27 (CH ), 88.00,
6
4
2
3
3
General procedure:
100.32, 123.15, 128.75, 130.17, 132.57, 135.27, 148.73, 161.56, 163.07 and
Aroyl chloride (2 mmol) was added by a syringe to ammonium
thiocyanate (0.15 g, 2 mmol) in a 50 mL flask at room temperature.
The reaction mixture was stirred in a water bath at about 90 °C for 5
min. Then, 4-hydroxy-6-methyl-2H-pyran-2-one (2 mmol) was added
at the same temperature. The reaction mixture was allowed to cool to
room temperature. Finally, N-methylimidazole (0.032 g) (10 mol%)
was added using a syringe. The resulting mixture was stirred at room
temperature for 6 h. The progress of the reaction was monitored by
TLC. After completion of the reaction, water (15 mL) was added over
193.84 ppm.
2-(4-Methylphenyl)-7-methyl-4-thioxo-4H-pyrano[3,4-e][1,3]
oxazin-5-one (4f): Yellow powder; m.p. 92–94 C, IR (KBr) (ν cm ):
17013, 1670, 1612, 1267, 1080. Anal. calcd for C H NO S: C, 63.14; H,
o
-1
max
15
11
3
3.89; N, 4.91; found: C, 63.31; H, 3.72; N, 5.07%. MS (m/z, %): 285 (7).
1
H NMR (400 MHz, CDCl ): δ 2.05 (3H, s, CH ), 2.31 (3H, s, CH ), 5.79
3
3
3
3
(1H, s, =CH), 7.46 (2H, d, J = 8Hz, 2CH of C H CH ), 8.15 (2H, d,
HH
6
4
3
3
JHH = 8Hz, 2CH of C H CH ) ppm. 13C NMR (100.6 MHz, CDCl ): δ
6
4
3
3
19.80 (CH ), 21.97 (CH ), 89.47, 101.32, 126.73, 128.62, 129.17, 130.08,
3
3
5
min to the reaction mixture. The resulting precipitate was collected
135.40, 144.25, 161.12, 165.66 and 194.07 ppm.
by filtration, washed with cold diethyl ether (10 mL) to give a pure
product.
Received 4 July; accepted 29 July 2015
Paper 1503471 doi: 10.3184/174751915X14383268906316
Published online: 7 August 2015
7
-Methyl-2-phenyl-4-thioxo-4H-pyrano[3,4-e][1,3]oxazin-5-one
o
-1
(
1
4a): Yellow powder; m.p. 70–72 C, IR (KBr) (νmax cm ): 1716, 1658,
627, 1257, 1041. Anal. calcd for C H NO S: C, 61.98; H, 3.34; N, 5.16;
found: C, 61.85; H, 3.21; N, 5.34%. MS (m/z, %): 271 (6). H NMR (400
MHz, CDCl ): δ 2.24 (3H, s, CH ), 5.95 (1H, s, =CH), 7.47–7.77 (5H, m,
CH of C H ) ppm. C NMR (100.6 MHz, CDCl ): δ 19.97 (CH ), 89.79,
14
9
3
1
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3
3
1
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1
1
6
5
3
3
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3
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(
14 8 3
5
6
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%
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3 3
3 3
s, =CH), 7.45 (2H, d, J = 8Hz, 2CH of C H Cl), 7.85 (2H, d, J =
HH
HH
6
4
13
8
(
Hz, 2CH of C H Cl) ppm. C NMR (100.6 MHz, CDCl ): δ 19.38
CH ), 88.00, 100.27, 122.94, 128.24, 129.36, 130.42, 135.53, 145.94,
6
4
3
7
8
9
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3
162.06, 164.28 and 193.52 ppm.
2
-(4-Bromophenyl)-7-methyl-4-thioxo-4H-pyrano[3,4-e][1,3]
10
o
oxazin-5-one (4c): Yellow powder; m.p. 132–134 C, IR (KBr)
νmax cm ): 1718, 1661, 1615, 1250, 1053. Anal. calcd for C H BrNO S:
C, 48.02; H, 2.30; N, 4.00; found: C, 48.13; H, 2.17; N, 3.90%. MS (m/z,
2
6, 348.
-1
(
11 M. A. Khalilzadeh, I. Yavari, Z. Hossaini and H. Sadeghifar, Monatsh.
Chem., 2009, 140, 467.
14
8
3