New synthesis of naphtho- and benzoxazoles: Decomposition of naphtho- and benzoxazinones with KOH

Article abstract of DOI:10.1081/SCC-100000190

A method that allows the synthesis of 4 different heterocyclic systems of fused aryl oxazoles, i.e., naphtho[1.2-d]. naphtho[2. 1-d]. naphtho[2.3-d]. and benzo[d]oxazoles in reasonable yield is described. This method consists of the decomposition of naphtho-and benzoxazinones with KOH.

Full text of DOI:10.1081/SCC-100000190

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NEW SYNTHESIS OF NAPHTHO- AND BENZOXAZOLES:
DECOMPOSITION OF NAPHTHO- AND
BENZOXAZINONES WITH KOH
Claudio Saitz a , Hernán Rodríguez a , Amelia Márquez a , Alvaro Cañete a , Carolina
Jullian a & Antonio Zanocco a
a Departamento de Química Orgánica y Físico-Química , Facultad de Ciencias Químicas y
Farmaceúticas Universidad de Chile , Casilla 233, Santiago, 1, Chile
Published online: 09 Nov 2006.
To cite this article: Claudio Saitz , Hernán Rodríguez , Amelia Márquez , Alvaro Cañete , Carolina Jullian & Antonio
Zanocco (2001) NEW SYNTHESIS OF NAPHTHO- AND BENZOXAZOLES: DECOMPOSITION OF NAPHTHO- AND BENZOXAZINONES
WITH KOH, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
31:1, 135-140, DOI: 10.1081/SCC-100000190
To link to this article: http://dx.doi.org/10.1081/SCC-100000190
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SYNTHETIC COMMUNICATIONS, 31(1), 135–140 (2001)
NEW SYNTHESIS OF NAPHTHO- AND
BENZOXAZOLES: DECOMPOSITION OF
NAPHTHO- AND BENZOXAZINONES
WITH KOH
Claudio Saitz,∗ Herna´n Rodr´ıguez, Amelia Ma´rquez,
Alvaro Can˜ete, Carolina Jullian, and Antonio Zanocco
Departamento de Qu´ımica Orga´nica y F´ısico-Qu´ımica,
Facultad de Ciencias Qu´ımicas y Farmaceu´ticas,
Universidad de Chile, Casilla 233, Santiago 1, Chile
ABSTRACT
A method that allows the synthesis of 4 different heterocyclic
systemsoffusedaryloxazoles, i.e., naphtho[1,2-d], naphtho[2,1-d],
naphtho[2,3-d], and benzo[d]oxazoles in reasonable yield is de-
scribed. This method consists of the decomposition of naphtho-
and benzoxazinones with KOH.
Benzoxazoleshave been obtained by heating o-aminophenolsand carboxylic
acids in the presence of polyphosphoric acid (1,2). The novel antibacterial agent
Boxazomicyn B has been synthesized by this method (3). Other options are the
Beckmann rearrangement of o-acylphenol oximes using zeolite catalysts (4) and,
morerecently, treatmentofN,O-diacylated2-aminophenolswithp-toluenesulfonic
acid under reflux in xylenes or toluene (5), or oxidative intramolecular cyclization
∗ To whom correspondence should be addressed. Fax: 562-678 2868; E-mail: clsaitz@
ll.ciq.uchile.cl
135
Copyright ꢀ 2001 by Marcel Dekker, Inc.
www.dekker.com
C

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SAITZ ET AL.
of phenolic Schiffs bases using iodobenzene diacetate as an oxidant (6), or man-
ganese triacetate, a relatively benign oxidizing reagent (7). On the other hand,
naphthoxazoles have been obtained, by cycloaddition of azomethine ylides (from
thermal cleavage of aziridines) to 1-nitroso-2-naphthol (8,9); by treatment of an
equimolecular mixture of 1-nitroso-2-naphthol and phenacyl piridinium bromide
with NaOH solution at −30◦C (10); by cycloaddition of masked azomethine ylide,
generated from 2-p-methoxyphenyl-4-phenyl-2-oxazolin-5-one, with 1-nitroso-2-
naphthol (11), and by reaction of 1,3-dipole, proceeding from 3-aroyl aziridines
cleavage, with 2-nitroso-1-naphthol. In this last reaction, naphthodiazepine is ob-
tained besides naphthoxazole (12). Some methods to obtain either benzo- or naph-
thoxazoles have been described: palladium-catalyzed condensation of aryl halides
with o-amino phenols or naphthols, followed by dehydrative cyclization (13); and
cycloadditionofo-hydroxyanilidesbyheatingwithaqueousHClat150◦C, (anilide
can be prepared in situ heating the corresponding o-substituted aniline with car-
boxylic acid, anhydride or acid chloride (14)). As an example, the benzoxazole
ringoftheantibioticCalcymicin(15)andtheanti-inflammatoryBenoxaprofen(16)
have been obtained by these methods. Reduction of the suitable 2-nitrophenyl, 2-
nitro-1-naphthyl or 1-nitro-2-naphthyl-benzoates or 4-nitrobenzoates with Sn-HCl
(17) is another suitable method, and 2-arylnaphtho[1,2-d]oxazoles have been pre-
pared by condensation of 1-amino-2-naphthol derivatives with aromatic aldehydes
in the presence of pyridine in BuOH (18).
Most of the existing methods referred to above consist of oxidative reactions
using uncommon oxidizing reagents, or they are cycloaddition reactions where
more than one product is obtained. The importance of the method we describe
lies on the easy and rapid way that these heterocyclic system are available. Both
substrate and product are heterocycles, the last readily obtained by decomposition
of the first.
In this work, the transformation of 2-phenyl-3H-naphtho[2,1-b][1,4]-
oxazin-3-one (1), 3-phenyl-2H-naphtho[1,2-b][1,4]oxazin-2-one (2), 3-phenyl-
2H-naphtho[2,3-b][1,4]-oxazin-2-one (3), and 3-phenyl-2H-benzo[b][1,4]oxazin-
2-one (4) on heating with KOH in MeOH to their corresponding naphtho- and
benzoxazoles: 2-phenylnaphtho[1,2-d]oxazole (5), 2-phenylnaphtho[2,1-
d]oxazole (6), 2-phenyl naphtho[2,3-d]oxazole (7) and 2-phenylbenzo[d]oxazole
(8), is described (Scheme 1).
Scheme 1.

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137
Table 1. Conversion of Aryl Oxazinones 1–4 into Aryloxazoles 5–8
Substrate Product Yield (%)
Entry
The oxazinones 1–4 were obtained, in satisfactory yields through a modifica-
tion of the Moffet’s method (19), which heats at 120◦C for 1.5 h an equimolecular
mixture of the respective o-aminophenol and -naphthol or their chlorohydrate with
the corresponding α-keto ester in pyridine as solvent.
We herein describe a rapid method that allows the synthesis of four differ-
ent heterocyclic systems of fused aryl oxazoles: naphtho[1,2-d]; naphtho[2,1-d];
naphtho[2,3-d]; and benzo[d]oxazoles in reasonable yields (Table 1), thus com-
plementing the existing methods to obtain these heterocyclic systems.
EXPERIMENTAL
Melting points were determined on a hot-stage apparatus and are
uncorrected. Spectra were recorded using the following instruments: IR, FT-IR
1
Bruker IFS 55; UV, ATI-UNICAM; H and 13C-NMR, Bruker DRX-300 (300
and 75 MHz), using tetramethylsilane as internal reference. Microanalyses were

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SAITZ ET AL.
determinated using Fisons EA 1108 analizer and were performed in CEPEDEQ
(Centro Para el Desarrollo de la Qu´ımica), Facultad de Ciencias Qu´ımicas y Far-
maceu´ticas, Universidad de Chile. Column chromatography was performed on
Merck silica gel 60, 230–400 mesh, and TLC- on Merck silica gel G.
General Procedure for Preparation of Naphtho- and
Benzoxazinones 1 to 4
A Modification of the Moffet’s Method
The required o-aminophenol and -naphthol, or their chlorohydrate and
methyl benzoyl formate, were mixed in pyridine as solvent under nitrogen and
the mixture was heated at 120◦C during 1.5–2 h. After this time, the reaction mix-
ture was poured into ice water. The precipitate was collected by filtration, washed
with water, and purified by column chromatography (chloroform) on silica gel.
All compounds gave satisfactory spectroscopic and analytical data. Rep-
resentative data for select compounds follows. Compounds 1 and 5 were fully
characterized by concerted use of one- and two-dimensional NMR techniques in
our previous paper (20).
2-Phenyl-3H-naphto[2,1-b] l,4-oxazin-3-one (1) was obtained in 95%
yield (crude) and 71% (purified). Recrystallization from carbon tetrachloride gave
yellow pales m.p 174◦–175◦C. Lit.19177◦–178◦C.1H NMR (CDCl3) δ: 8.86 (d, Jd
8.3 Hz, 1H), 8.53 (m, 2H), 7.93 (d, Jd 8.78 Hz, 1H), 7.86 (d, Jd 8.78 Hz, 1H),
7.71 (d, Jd 8.78 Hz,1H), 7.58 (dd, 1H), 7.55 (m, 3H), 7.39 (d, Jd 9.0 Hz,1H), 13
C
NMR (CDCl3) δ: 152.67, 148.28, 144.22, 134.50, 132.35, 131.31, 131.02, 130.45,
129.48, 128.40, 128.22, 128.03, 126.67, 126.30, 122.84, 115.64.
3-Phenyl-2H-naphto[1,2-b] l,4-oxazin-2-one (2) was obtained in 85%
yield (crude). Recrystallization from carbon tetrachloride gave yellow pales m.p.
166◦–167◦C 1H NMR (CDCl3) δ: 8.48 (m, 2H), 8.42 (m, 2H), 7.89 (m, 1H), 7.83
(d, Jd 8.78 Hz, 1H), 7.77 (d,Jd 8.81 Hz, 1H), 7.65 (m, 2H), 7.53 (m, 3H). 13C
NMR (CDCl3) δ: 152.41, 150.04, 142.62, 134.35, 134.26, 131.34, 129.34, 128.72,
128.43, 128.02, 127.90, 127.30, 125.63, 125.46, 126.30, 122.55, 122.13, 115.65.
IR (Kbr) ν/cm−1: 1724 (C O), 1639 (C N). Anal. Calcd. for C18H11NO2: C,
79.11; H, 4.06; N, 5.13. Found: C, 79.04; H, 4.06; N, 5.21.
==
==
3-Phenyl-2H-naphtho[2,3-d] l,4-oxazin-2-one (3) was obtained in 60%
yield (crude). Recrystallization from acetonitrile gave yellow pales m.p. 201◦–
203◦C. 1H NMR (CDCl3) δ: 8.37 (m, 2H), 8,34 (s,1H), 8.12 (d, Jd 7.93 Hz; 1H),
7.88 (d, Jd 7.96 Hz, 1H), 7.67 (s, 1H), 7.56 (m, 5H). 13CNMR (CDCl3) δ: 152.15,
151.02, 144.20, 134.24, 139.95, 131.48, 130.95, 130.82, 129.57, 129.21, 128.87,

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139
128.44, 128.41, 127.41, 126.03, 125.89, 112.27. IR (Kbr) ν/cm−1: 1724 (C O),
==
==
1639 (C N). Anal. Calcd. for C18H11NO2: C, 79.11; H, 4.06; N, 5.13. Found: C,
78.99; H, 4.03; N, 5.40.
3-Phenyl–2H-benzo[d]-l,4-oxazin-2-one (4) was obtained in 85% yield.
Recrystallization from methanol gave light yellow pales m.p. 118–119◦C 1H NMR
(CDCl3) δ: 8.34 (dd, Jd S. 17; Jd 2.09 Hz, 2H), 7.85 (dd, Jd 7.90; Jd 1.55 Hz, 1H),
7.52 (m, 4H), 7.39 (td, J 7.70; J 7.62; J 1.30 Hz, 1H); 7.33 (dd, Jd 8.17; Jd 1.25 Hz,
1H). 13C NMR (CDCl3) δ: 152.26, 150.85, 146.47, 134.13, 131.66, 131.41, 131.11,
129.44, 128.37, 125.87, 116.16.
Typical Procedure for Transformation of Naphtho- and
Benzoxazinones in Naphtho- and Benzoxazoles 5 to 8
-Phenyl-3H-naphtho[2,1-b] l,4-oxazinone (40 mg, 0.146 mmol) and 10%
KOH solution (2mL) were refluxed in MeOH for 30 min. Immediately, the so-
lution became an intense brownish red. The mixture was left overnight and then
neutralizad with acetic acid (10%). The precipitate was collected by filtration,
washed with water, and purified by column choromatography (chloroform) on
silica gel.
2-Phenylnaphtho[1,2-d]oxazole (5) Recrystallization from ligroin gave
whiteneedles, m.p. 122◦–123◦C. Lit. (9)125◦–130◦C, Lit. (21)131◦C. SeeAbbady
(21) for synthesis of 5; however, nmr data were not reported. 1H-RMN (CDCl3) δ
8.63 (d, Jd 8.20 Hz, 1H), 8.37 (m, 2H), 8.01 (d, Jd 8.20 Hz, 1H), 7.84 (d, Jd 8.90 Hz,
1H), 7.76 (d, Jd 8.90 Hz, 1H), 7.71 (m, 1H), 7.58 (m, 4H). 13C-RMN (CDCl3) δ:
162.25, 148.09, 137.66, 130.96, 128.80, 128.48, 127.48, 127.27, 126.87, 126.64,
125.91, 125.27, 122.21, 110.53.
2-Phenylnaphtho[2,1-d]oxazole (6) m.p. 122◦C. 1H-RMN (CDCl3) δ: 8.30
(m, 3H), 7.96 (d, Jd 8.24 Hz, 1H), 7.91 (d, Jd 8.73 Hz, 1H), 7.78 (d, Jd 8.74 Hz, IH),
7.63 (td, J 9.0; J 9,0; J 1.14 Hz, 1H) (m, 1H), 7.54 (m, 4H). 13C-RMN (CDCl3)
δ: 162.43, 146.45, 138.60, 131.7, 131.14, 128.92, 128.68, 127.41, 127.29, 126.82,
125.62, 125.40, 125.03, 124.51, 119.98, 110.53.
2-Phenylnaphtho[2,3-d]oxazole (7) m.p. 203◦–205◦C. 1H-RMN (CDCl3)
δ: 8.34 (m, 2H), 8.20 (s, 1H), 7.99 (m, 2H), 7.95 (s, 1H), 7.55 (m, 3H), 7.49
(m, 2H). 13C-RMN (CDCl3) δ: 165.04, 149.73, 142.07, 132.08, 131.77, 131.56,
128.97, 128.53, 128.14, 127.91, 126.96, 125.47, 124.69, 117.33, 106.35.
1
2-Phenylbenzo [d]oxazole (8) m.p. 100◦–102◦C Lit (7) 101◦C. H-RMN
(CDCl3) δ: 8.24 (m, 2H), 7.77 (m, 1H), 7.54 (m, 1H), 7.49 (m, 3H), 7.32 (m, 2H).
13C-RMN (CDCl3,) δ: 162.96, 150.71, 142.10, 131.43, 128.83, 127.57, 127.14,
125.03, 124.51, 119.98, 110.53.

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ACKNOWLEDGMENTS
We thank the FONDECYT, Project 1940446 and DTI, Project Q 3336-
9323 Universidad de Chile, for the financial support and CEPEDEQ for use of
instruments. A. Can˜ete thanks CONICYT for a fellowship.
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Received April 6, 2000

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