Studies on condensation of chlorocarbonyl phenyl ketene with N-unsubstituted amides: Synthesis of some new 1,3-oxazin-6-ones

Article abstract of DOI:10.1007/s11172-008-0374-3

A series of 1,3-oxazin-6-one derivatives has been synthesized upon treatment of N-unsubstituted amides with chlorocarbonyl phenyl ketene under reflux in toluene for several minutes. In this simple way, 2,5-disubstituted derivatives of 1,3-oxazin-6-ones have been obtained in high yields.

Full text of DOI:10.1007/s11172-008-0374-3

Russian Chemical Bulletin, International Edition, Vol. 57, No. 12, pp. 2600—2602, December, 2008
2600
Brief Communications
Studies on condensation of chlorocarbonyl phenyl ketene
with Nꢀunsubstituted amides: synthesis of some new 1,3ꢀoxazinꢀ6ꢀones
H. Sheibani, K. Saidi, and H. Foroughi
Shahid Bahonar University of Kerman, Department of Chemistry,
Kerman, 76169 Iran.
Fax: +98 341 322 1452. Eꢀmail: hsheibani@mail.uk.ac.ir
A series of 1,3ꢀoxazinꢀ6ꢀone derivatives has been synthesized upon treatment of Nꢀunsubꢀ
stituted amides with chlorocarbonyl phenyl ketene under reflux in toluene for several minutes.
In this simple way, 2,5ꢀdisubstituted derivatives of 1,3ꢀoxazinꢀ6ꢀones have been obtained
in high yields.
Key words: chlorocarbonyl phenyl ketene, Nꢀunsubstituted amides, 1,3ꢀoxazinꢀ6ꢀones.
Scheme 1
1,3ꢀOxazinꢀ6ꢀones (3ꢀazaꢀαꢀpyrones) are sixꢀmemꢀ
bered heterocyclic compounds, which are known as imꢀ
portant substrates in heterocyclic transformations, espeꢀ
cially in the reactions of [4+2]ꢀcycloaddition of their
2ꢀazadiene fragment with many dienophiles, leading to
pyridines after elimination of CO2.1 The synthesis of the
first member of the series, 4ꢀhydroxyꢀ6Hꢀ1,3ꢀoxazinꢀ6ꢀ
one, has been described2 together with a detailed review of
preparative methods for the substituted derivatives. The
most common method for the synthesis of 1,3ꢀoxazinꢀ6ꢀ
ones is the cyclization of 3ꢀacylaminoacrylic acids and
esters, as a rule, under thermal conditions, presumably
through the intermediate formation of acylimino ketenes,
which undergo electrocyclization into the 1,3ꢀoxazinꢀ6ꢀ
one derivatives (Scheme 1).3
version into 3ꢀazabicyclo[3.1.1]heptanetriones by sequenꢀ
tial facile ring opening and recyclization through the reacꢀ
tion of [2+2]ꢀcrossꢀcycloaddition (Scheme 2).
Chlorocarbonyl ketenes proved very efficient 1,3ꢀdiꢀ
electrophilic agents, capable of undergoing the reaction
Recently,4 we have discovered a reaction of chlorocarꢀ
bonyl ketenes with Nꢀsubstituted cinnamic amides, leadꢀ
ing to 2ꢀvinylꢀ1,3ꢀoxaziniumꢀ4ꢀolates, as well as their conꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2549—2551, December, 2008.
1066ꢀ5285/08/5712ꢀ2600 © 2008 Springer Science+Business Media, Inc.

Condensation of chlorocarbonyl phenyl ketene
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 12, December, 2008
2601
Scheme 2
Scheme 3
with a wide variety of binucleophiles under mild condiꢀ
tions. They were predominantly used in the synthesis of
fiveꢀ and sixꢀmembered heterocycles functionalized with
hydroxy groups in 1,3ꢀpositions.5,6 In continuation of
our study on the reactions of chlorocarbonyl ketenes
with 1,2ꢀdinucleophiles (oximes7 and hydrazones8) and
1,3ꢀdinucleophiles (1,3ꢀdicarbonyl compounds,9,10 thioꢀ
amides, and amides11), we studied a facile condensation
of chlorocarbonyl phenyl ketene with Nꢀunsubstitutꢀ
ed amides and synthesized some new 1,3ꢀoxazine derivaꢀ
tives (Scheme 3).
In comparison with other multistep methods, this synꢀ
thesis is of interest for the simple and efficient oneꢀpot
procedure. Another advantage of the method consists in
the availability of the starting compounds, short reaction
time, and high yields of the target products. The condenꢀ
sation of isolable and stable ketene 1 with Nꢀunsubstituted
α,βꢀunsaturated amides or aromatic amides 2 in boiling
toluene gives the high yields of 4ꢀhydroxyꢀ1,3ꢀoxazinꢀ6ꢀ
ones 3a—d. At the same time, Nꢀunsubstituted aliphatic
amides lead to a mixture of two tautomers: 1,3ꢀoxazinꢀ6ꢀ
one 4A and 1,3ꢀoxazinꢀ4,6ꢀdione 4B in good yields
(see Scheme 3).
Comꢀ
pound
R
Yield
(%)
Comꢀ
pound
R
Yield
(%)
3a
75
3d
85
The structures of compounds 3a—d and 4a,b have been
1
inferred from the IR, H and 13C NMR spectroscopic
3b
3c
90
92
4a
4b
PhCHBrCHBr— 75
70
and mass spectrometric data. The IR spectrum of comꢀ
pound 3a contains a broad band of the hydroxy group at
3180—2500 cm–1, the band of the carbonyl group at
1741 cm–1, and an intensive band at 1595 cm–1 related to
1
the C=N bond. In the H NMR spectrum of compound
proton at C(5) of the minor tautomer B of compound
4a.12,13 The quantitative analysis of the mixtures was perꢀ
form by the integration of signals in the 1H NMR spectra.
3a, four signals are present along with a downfield signal
for the enolic OH group (δ 12.78). Such an assignment
agrees with the literature data for similar compounds.
The 1H and 13C NMR spectra of compounds 4a,b indiꢀ
cate the presence of two tautomers. Thus, in the 1H NMR
spectrum the signal at δ 11.64 is present, which correꢀ
sponds to the OH group of tautomer A of compound 4a,
and the signal at δ 5.62, which has been assigned to the
Experimental
Commercially available reagents (Merck, Fluka) were used
without additional purification. Melting points were measured
using Gallenkamp apparatus (Great Britain) and were not corꢀ

2602
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 12, December, 2008
Sheibani et al.
rected. IR spectra were recorded on a Matson 1000 FT IR specꢀ
trometer (KBr pellets). 1H and 13C NMR spectra were recorded
on a Bruker DRXꢀ500 spectrometer in DMSOꢀd6. Chemical
shifts marked with asterisk are given for two tautomers. Mass
spectra were obtained on a Shimadzu QP2000A instrument
(70 eV). Chlorocarbonyl phenyl ketene (1) was obtained similarꢀ
ly to the procedure reported earlier.14
Compounds 3a—d and 4a,b (general procedure). A solution of
compound 1 (0.36 g, 2 mmol) in anhydrous THF (5 mL)
was added dropwise over 2 min to a stirred boiling solution of
Nꢀunsubstituted amide 2 (2 mmol) in toluene (20 mL). An imꢀ
mediate precipitation of colored products 3 or 4 was observed.
The reaction mixture was cooled, the precipitate was filtered off,
washed with anhydrous diethyl ether, and recrystallized from
anhydrous ethyl acetate—hexane.
4ꢀHydroxyꢀ5ꢀphenylꢀ2ꢀ[(E)ꢀ1ꢀethylꢀ2ꢀ(2ꢀfuryl)]ꢀ6Hꢀ1,3ꢀ
oxazinꢀ6ꢀone (3a). The yield was 0.42 g (75%), orange crystals,
m.p. 180—182 °C. Found (%): C, 68.12; H, 3.76; N, 4.69.
C16H11NO4. Calculated (%): C, 68.33; H, 3.94; N, 4.98. IR,
ν/cm–1: 3180—2500 (br, OH), 1741 (C=O), 1595 (C=N).
1H NMR, δ: 12.78 (s, 1 H, OH); 7.97 (d, 1 H, βꢀCH, 3J = 16 Hz);
7.96—6.70 (m, 8 H, H arom.); 6.44 (d, 1 H, αꢀCH, 3J = 16 Hz).
13C NMR, δ: 165.52 (C=O), 160.64, 150.79, 147.22, 131.73,
130.53, 130.34, 127.86, 127.11, 117.95, 114.75, 113.67, 94.72.
MS, m/z (Irel (%)): 281 [M]+ (29), 280 [M – H]+ (44), 253
[M – CO]+ (15), 120 (100), 118 (29), 77 (15).
2ꢀ(3ꢀChlorophenyl)ꢀ4ꢀhydroxyꢀ5ꢀphenylꢀ6Hꢀ1,3ꢀoxazinꢀ6ꢀ
one (3b). The yield was 0.53 g (90%), yellow crystals, m.p.
214—216 °C. Found (%): C, 63.80; H, 3.23; N, 4.49. C16H10ClNO3.
Calculated (%): C, 64.12; H, 3.36; N, 4.67. IR, ν/cm–1: 3200—2500
(br, OH), 1701 (C=O), 1615 (C=N). 1H NMR, δ: 12.88 (s, 1 H,
OH); 8.07—7.27 (m, 9 H, H arom.). 13C NMR, δ: 165.49 (C=O),
160.89, 160.63, 134.21, 133.53, 131.51, 131.41, 131.34, 130.54,
127.95, 127.69, 127.00, 126.55, 95.75. MS, m/z (Irel (%)): 301
[M + 2]+ (28), 299 [M]+ (100), 271 [M – CO]+ (65), 139 (65),
105 (48), 78 (90), 77 (15).
2ꢀ(4ꢀChlorophenyl)ꢀ4ꢀhydroxyꢀ5ꢀphenylꢀ6Hꢀ1,3ꢀoxazinꢀ6ꢀ
one (3c). The yield was 0.55 g (92%), yellow crystals, m.p.
238—240 °C. Found (%): C, 64.05; H, 3.29; N, 4.56. C16H10ClNO3.
Calculated (%): C, 64.12; H, 3.36; N, 4.67. IR, ν/cm–1: 3180—2500
(br, OH), 1695 (C=O), 1605 (C=N). 1H NMR, δ: 12.90 (s, 1 H,
OH); 8.11—7.26 (m, 9 H, H arom.). 13C NMR, δ: 165.62 (C=O),
161.38, 160.71, 138.83, 131.43, 130.56, 130.20, 129.78, 128.56,
127.92, 127.31, 95.47. MS, m/z (Irel (%)): 301 [M + 2]+ (30), 299
[M]+ (100), 271 [M – CO]+ (60), 139 (65), 105 (48), 77 (15).
4ꢀHydroxyꢀ2ꢀ(4ꢀnitrophenyl)ꢀ5ꢀphenylꢀ6Hꢀ1,3ꢀoxazinꢀ6ꢀ
one (3d). The yield was 0.52 g (85%), yellow crystals, m.p.
230—232 °C. Found (%): C, 61.55 H, 3.11; N, 9.12. C16H10N2O5.
Calculated (%): C, 61.94; H, 3.25; N, 9.03. IR, ν/cm–1: 3200—2550
(br, OH), 1691 (C=O), 1595 (C=N). 1H NMR, δ: 12.80 (s, 1 H,
OH); 8.42—7.26 (m, 9 H, H arom.). 13C NMR, δ: 166.57 (C=O),
165.39, 160.59, 150.37, 140.36, 135.31, 131.23, 130.53, 129.81,
129.28, 127.98, 124.57, 123.78, 96.25. MS, m/z (Irel (%)): 310
[M]+ (100), 282 [M – CO]+ (65), 150 (97), 118 (79), 104 (25).
2ꢀ(1,2ꢀDibromoꢀ2ꢀphenylethyl)ꢀ5ꢀphenylꢀ6Hꢀ1,3ꢀoxazinꢀ6ꢀ
one (4a). The yield was 0.63 g (70%), yellow crystals, m.p.
150—152 °C. IR, ν/cm–1: 3220—2800 (br, OH), 1717, 1690, 1660.
MS, m/z (Irel (%)): 451 [M]+ (10), 423 [M – CO]+ (20), 371 (18),
369 (20), 346 (22), 344 (35), 290 (60), 228 (100), 226 (95),
257 (25), 250 (40), 181 (70), 183 (95), 131 (55), 118 (70), 103 (35),
101 (20), 91 (10).
Major tautomer, 2ꢀ(1,2ꢀdibromoꢀ2ꢀphenylethyl)ꢀ4ꢀhydroxyꢀ
5ꢀphenylꢀ6Hꢀ1,3ꢀoxazinꢀ6ꢀone (form A) (60%). 1H NMR, δ:
11.64 (s, 1 H, OH); 7.91—7.04 (m, 20 H, H arom.)*; 5.91, 5.77
(both d, 1 H each, 3J = 14 Hz). 13C NMR, δ: 168.61, 165.38,
164.27, 160.16 (C=O, C(2), C(4))*, (139.22, 138.02, 130.56,
129.91, 129.80, 129.63, 129.33, 129.27, 129.14, 128.91, 128.69,
128.65, 128.49, 127.74)*, 96.05 (C(5)), (52.24, 51.49, 49.23,
48.04)*. Minor tautomer, 2ꢀ(1,2ꢀdibromoꢀ2ꢀphenylethyl)ꢀ5ꢀ
phenylꢀ4Hꢀ1,3ꢀoxazinꢀ4,6(5H)ꢀdione (form B) (40%). 1H NMR,
δ: 5.51, 5.18 (both d, 1 H each, 3J = 10 Hz); 5.62 (s, 1 H, H(5)).
13C NMR, δ: 50.69 (C(5)).
2ꢀCyclohexylꢀ5ꢀphenylꢀ6Hꢀ1,3ꢀoxazine (4b). The yield was
0.40 g (75%), yellow crystals, m.p. 196—198 °C. Found (%):
C, 70.65; H, 6.21; N, 5.03. C16H17NO3. Calculated (%): C, 70.83;
H, 6.32; N, 5.16. IR, ν/cm–1: 3150—2700 (br, OH), 1727, 1690,
1650. MS, m/z (Irel (%)): 271 [M]+ (58), 245 (50), 243 [M – CO]+
(30), 188 (20), 161 (20), 145 (22), 127 (58), 118 (100), 99 (35),
83 (65), 72 (25), 40 (45).
Major tautomer, 2ꢀcyclohexylꢀ4ꢀhydroxyꢀ5ꢀphenylꢀ6Hꢀ1,3ꢀ
oxazinꢀ6ꢀone (form A) (70%). 1H NMR, δ: 12.25 (s, 1 H, OH);
7.47—7.23 (m, 10 H, H arom.)*; 2.50—1.15 (m, 22 H, cycloꢀ
C6H13)*. 13C NMR, δ: 177.75, 176.69, 172.48, 172.09, 170.03,
169.15, 165.44, 161.26 (C=O, C(2), C(4))*, (135.21, 130.48,
129.96, 129.85, 128.56, 128.47, 127.88, 127.10, 126.95, Ph)*,
94.35 (CM5), (44.55, 44.06, 43.55, 42.80, 29.56, 28.88, 25.91,
25.70, 25.26, cyclohexyl)*. Minor tautomer, 2ꢀcyclohexylꢀ5ꢀ
phenylꢀ4Hꢀ1,3ꢀoxazinꢀ4,6(5H)ꢀdione (form B) (30%). 1H NMR,
δ: 5.20 (s, 1 H, H(5)). 13C NMR, δ: 59.21 (C(5)).
Authors appreciate a support of the Shahid Bahonar
University of Kerman.
* For two tautomers.
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Received March 30, 2007;
in revised form September 26, 2007