September 2009
An Efficient One-Pot Synthesis of Naphthoxazinones by a Three-Component
Coupling of Naphthol, Aldehydes, and Urea Catalyzed by Zinc Triflate
1021
Table 3
Na2SO4. The residue was concentrated and recrystallized from
EtOAc-hexane to afford the pure product as a white powder
(451 mg, 82%), mp 216–218ꢀC (reported 218–220ꢀC) [6a].
Typical procedure for the synthesis of 4-phenyl-3,4-dihy-
dronaphtho[1,2-e][1,3]oxazin-2-one (Table 3, 6a). The pro-
cedure reported in the previous experiment was followed using
a-naphthol in place of b-naphthol. The corresponding pure
product was obtained as a white powder (352 mg, 64%), mp
195–197ꢀC (reported 196–198ꢀC) [4].
Zn(OTf)2-catalyzed reaction of a-naphthol with
aromatic aldehydes and urea.
Product 6
Ar
Time (h)
Yield (%)a
Ref.
4
a
b
Ph
4-MeC6H4
5
6
64
67
The spectral (IR, 1H, and 13C NMR) data and elemental
analyses of the compounds which are not readily found are
provided later.
c
7
69
a Yields refer to isolated pure product.
1-Benzo[1,3]dioxol-5-yl-1,2-dihydronaphtho[1,2-e][1,3]oxa-
zin-3-one (Table 2, 4d). This compound was obtained accord-
ing to the above procedure as white powder, mp 164–166ꢀC;
derivatives by further heating. It should be pointed out
that 4-nitrobenzaldehyde and 3-nitrobenzaldehyde
reacted with urea and b-naphthol but the reaction
stopped at intermediate stage 7 [10]. The reaction did
not proceed further on long time heating.
1
IR (KBr): 3321, 1701, 1447 cmꢂ1; H NMR (DMSO-d6): d ¼
8.42 (br s, 1H), 7.89–7.84 (m, 2H), 7.64–7.60 (m, 2H), 7.46–
7.41 (m, 2H), 7.32–7.27 (m, 1H), 6.83–6.71 (m, 3H), 6.01 (d,
J ¼ 4.0 Hz, 1H), 5.91 (d, J ¼ 4.0 Hz, 1H); 13C NMR
(DMSO-d6): d ¼ 149.5, 147.8, 147.6, 147.1, 137.0, 130.6,
130.4, 129.1, 128.8, 127.6, 125.3, 123.4, 120.6, 117.1, 114.2,
108.6, 107.5, 101.4, 53.6; Anal. Calcd for C19H13NO4: C
71.47, H 4.10, N 4.39. Found: C 71.31, H 3.98, N 4.21.
CONCLUSIONS
4-p-Tolyl-3,4-dihydronaphtho[2,1-e][1,3]oxazin-2-one (Table 3,
6b). This compound was obtained according to the above pro-
cedure as white powder, mp 214–216ꢀC; IR (KBr): 3244,
In conclusion, the work presented here demonstrates a
straightforward and general procedure for the efficient
one-pot synthesis of naphthoxazinones by a three-com-
ponent coupling of naphthols, aromatic aldehydes, and
urea. The reaction possesses the following synthetic fea-
tures: (a) mild conditions, (b) simple operation, (c) good
yields, (d) nontoxic and cheap metal catalyst, (e) the
compatibility with various functional groups, and (f)
applicability for an easy synthesis of 1-aryl-1,2-dihydro-
naphtho[1,2-e][1,3]oxazin-3-ones and 4-aryl-3,4-dihydro-
naphtho[2,1-e][1,3]oxazin-2-ones.We believe that this
procedure will provide a better and more practical alter-
native to the existing methodologies for the synthesis of
naphthoxazinone derivatives. Further investigations to
broaden the scope of this methodology toward pharma-
ceuticals and chiral products are in progress.
1723, 1371 cmꢂ1
;
1H NMR (DMSO-d6): d ¼ 8.71 (s, 1H),
8.15 (d, J ¼ 7.9 Hz, 1H), 7.90 (d, J ¼ 7.9 Hz, 1H), 7.65–7.55
(m, 3H), 7.16–7.23 (m, 2H), 7.18–7.13 (m, 3H), 5.78 (s, 1H),
2.25 (s, 3H); 13C NMR (DMSO-d6): d ¼ 149.2, 143.3, 140.3,
137.3, 133.0, 129.4 (2C), 127.8, 127.0, 126.9, 126.8 (2C),
124.0, 123.7, 122.5, 120.5, 116.3, 56.0, 20.6; Anal. Calcd for
C19H15NO2: C 78.87, H 5.23, N 4.84. Found: C 78.53, H 5.02,
N 4.65.
4-(3,4,5-Trimethoxyphenyl)-3,4-dihydronaphtho[2,1-e][1,3]oxa-
zin-2-one (Table 3, 6c). This compound was obtained according
to the above procedure as white powder, mp 228–230ꢀC ; IR
1
(KBr): 2926, 1754, 1592, 1376 cmꢂ1; H NMR (DMSO-d6): d
¼ 8.68 (s, 1H), 8.14 (d, J ¼ 7.9 Hz, 1H), 7.93 (d, J ¼ 7.9 Hz,
1H), 7.67–7.57 (m, 3H), 7.23 (d, J ¼ 8.5 Hz, 1H), 6.70 (s,
2H), 5.79 (s, 1H), 3.73 (s, 6H), 3.63 (s, 3H); 13C NMR
(DMSO-d6): d ¼ 153.1 (2C), 149.1, 143.2, 138.7, 137.1,
133.1, 127.8, 127.0, 126.9, 124.0, 123.6, 122.4, 120.5, 115.8,
104.2 (2C), 60.0, 56.4, 55.9 (2C); Anal. Calcd for C21H19NO5:
C 69.03, H 5.24, N 3.83. Found: C 68.89, H 5.06, N 3.67.
EXPERIMENTAL
Melting points were determined on a glass disk with an
electrical bath and are uncorrected. 1H NMR (300 MHz) and
13C NMR (75 MHz) spectra were run in DMSO-d6 solutions.
IR spectra were taken as KBr plates. Elemental analyses were
done by Perkin-Elmer autoanalyzer. Zn(OTf)2 was purchased
from Aldrich. All liquid reagents were distilled before use.
Typical procedure for the synthesis of 1-phenyl-1,2-dihy-
dronaphtho[1,2-e][1,3]oxazin-3 one (Table 2, 4a). A solution
of benzaldehyde (212 mg, 2 mmol, 203 lL), b-naphthol (288
mg, 2 mmol), and urea (180 mg, 3 mmol) in CH3CN (4 mL)
was heated under reflux (90–95ꢀC) in the presence of zinc tri-
flate (73 mg, 10 mol%) for 5 h (TLC). At completion, the
reaction mixture was distilled under vacuum to remove the sol-
vent and then diluted with cold water (10 mL). After extrac-
tion with ethyl acetate (20 mL ꢁ 3), the combined organic
layers were washed with brine and dried over anhydrous
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet