Synthesis and some transformations of 2-(2-Furyl)naphtho[1,2-d]oxazole

Article abstract of DOI:10.1134/S1070428011050095

By condensation of 1-amino-2-hydroxynaphthalene with furoyl chloride in 1-methyl-2-pyrrolidone 2-(2-furyl)naphtho[1,2-d]oxazole was synthesized and brought into electrophylic substitution reactions: nitration, bromination, sulfonation, formylation, and acylation. The substituent commonly was introduced into the position 5 of the furan ring, but at the nitration and bromination electrophilic attack was directed both at the furan ring and the naphthalene fragment. Pleiades Publishing, Ltd., 2011.

Full text of DOI:10.1134/S1070428011050095

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 5, pp. 710−713. © Pleiades Publishing, Ltd., 2011.
Original Russian Text ©A.A. Aleksandrov, A.S. Dedeneva, M.M. El’chaninov, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 5, pp. 707−709.
Synthesis and Some Transformations
of 2-(2-Furyl)naphtho[1,2-d]oxazole
A. A. Aleksandrov, A. S. Dedeneva, and M. M. El’chaninov
Southern Russian State Technical University (Novocherkassk Polytechnic Institute)
Novocherkassk,346428 Russia
e-mail: aaanet1@yandex.ru
Received June 22, 2010
Abstract—By condensation of 1-amino-2-hydroxynaphthalene with furoyl chloride in 1-methyl-2-pyrrolidone
2-(2-furyl)naphtho[1,2-d]oxazole was synthesized and brought into electrophylic substitution reactions: nitration,
bromination, sulfonation, formylation, and acylation. The substituent commonly was introduced into the position
5 of the furan ring, but at the nitration and bromination electrophilic attack was directed both at the furan ring and
the naphthalene fragment.
DOI: 10.1134/S1070428011050095
Among the fields of heterocyclic chemistry attracting
a high attention the chemistry of bihetaryls, compounds
built of two heteroaromatic moieties linked by an ordi-
nary bond, should be singled out. They are applied as
pharmaceuticals and pesticides. The reciprocal influence
of heterocyclic fragments in bihetaryls is an interesting
and yet insufficiently studied problem both from the
viewpoint of their structure and reactivity.
of various heterocyclic substituents in the system. For
instance, the analysis of 1H NMR spectra of compounds
Ia and IIa reveals a distinct correlation between the
downfield shift of the H3 protons of the furan ring (7.30
and 7.15 ppm) governed first of all by the induction ef-
fect and the degree of the electron-acceptor influence
of the naphthooxazole or imidazole substituents that is
smaller in the latter case. Therefore the relative reactiv-
ity of furan ring in compound Ia should be expected to
be lower.
Publications are virtually lacking on furyl derivative
of naphtho[1,2-d]oxazole Ia, and in this connection
we have decided to develop or to choose a convenient
method of its synthesis, to investigate its relative reac-
tivity and to compare the latter with that of previously
studied [1, 2] naphthoimidazole analog IIa.
The reactions carried out confirm this assumption.
For instance, in the nitration by treating with a complex
of Cu(NO3)2 and acetic anhydride the initial compound
Ia was mainly recovered, whereas compound IIa un-
der these conditions gave a 5,5-dinitro derivative in
the furan and naphthalene rings. The nitration product
2-(2-Furyl)naphtho[1,2-d]oxazole (Ia) we obtained
for the first time by the condensation of 1-amino-2-
hydroxynaphthalene with furoyl chloride in 1-methyl-
2-pyrrolidone (yield 67%), and it was brought into elec-
trophylic substitution reactions: nitration, bromination,
sulfonation, formylation, acylation (Scheme 1).
Scheme 1.
N
N
The main trend in the investigation of compounds
of furan series and its isologs by NMR spectroscopy
consists in the comparison of the chemical shifts and
coupling constants of initial heterocycles and their
derivatives. Proceeding from such comparison it is pos-
sible with respect to bihetaryls to estimate the influence
O
O
N
O
Me
IIa
Ia
R = NO2 (b), Br (c), H (d), Me (e), Ph (f).
710

SYNTHESIS AND SOME TRANSFORMATIONS OF 2-(2-FURYL)NAPHTHO[1,2-d]OXAZOLE
711
Scheme 2.
HNO3 or
Br_DCE
RCO2H or
(CH2)6N4 in PPA
N
N
N
O
_H2O, _CH2O
_HBr
O
O
R
O
O
R
O
O
R
Ia
Id_If
Ib, Ic
of compound Ia we succeeded to obtain by its boil-
ing in dilute nitric acid (d 1.32 g/cm3). According to
the H NMR spectrum it proved to be also 5,5-dinitro
derivative Ib. Analogous result was also obtained by
the bromination of naphthooxazole Ia at boiling in
dichloroethane (Scheme 2). The yield of 5-bromo-2-(5-
bromo-2-furyl)-naphtho[1,2-d]oxazole (Ic) was 66%.
Compound IIa furnished a similar dibromo derivative
already at –5°C [1], but compound Ia under these condi-
tions was recovered.
carried out with benzoic acid in polyphosphoric acid at
160°C (Scheme 2). In contrast to analogous transforma-
tion of compound IIa it occurred with difficultly and
with a low yield of ketone If. Unlike that compound IIa
afforded 5-benzoyl derivative in 4–6 h with 70% yield,
whereas the yield of 2-(5-benzoyl-2-furyl)naphtho[1,2-
d]oxazole (If) in 12 h did not exceed 43%, and about
45% of initial compound Ia was recovered.
1
The acidophobic five-membered heterocycles of
pyrrole type are known to undergo sulfonation by the
adduct of sulfuric anhydride with pyridine. At the same
time the sulfonation of the majority of 2-hetarylimid-
azoles succeeded only at the action of concn. sulfuric
acid in polyphosphoric acid. We failed to perform the
sulfonation of compound Ia by both first and second
procedures. Evidently this is caused by the existence of
sulfonic acids in betaine form whose stability depends
on the basicity of the naphthooxazole fragment which
is known to be the lowest among azoles [5].
The formylation of five-membered π-excessive
heterocycles and their derivatives is now successfully
performed by Vilsmeier reaction. However according
to [3] this method not always is successful with the
majority of hetarylimidazoles. It turned out that com-
pound Ia also was inert with respect to the complex
DMF–POCl3, therefore we carried out its formylation
with hexamethylenetetramine in polyphosphoric acid
at 90–100°C. The yield of aldehyde Id was only 41%.
The rest of initial compound was transformed into
intermediate products which we failed to isolate and
identify. Compound IIa under similar conditions re-
acted already at 60°C with the 75% yield of 5-formyl
derivative at the furan ring.
Alongside imidazoles and thiazoles some derivatives
of 2-furyloxazole are known as antiparasitic agents.
The study of their 5-nitro derivatives showed that they
exhibited a high antihelmintic activity [6].
In keeping with published data [1], the acetylation
of compound IIa was performed by treating with ace-
tic anhydride at 100–110°C in polyphosphoric acid.
We succeeded to acetylate compound Ia by boiling in
acetic anhydride in the presence of catalytic quantity of
anhydrone, namely, under mild conditions of G.N. Doro-
feenko reaction [4]. Apparently, here compound Ia is
acylated in the form of base where the electron-acceptor
property of the naphthooxazole fragment are consid-
erably reduced and it is also favored by its very low
basicity [5]. The yield of 5-acetyl derivative Ie was
relatively high (78%).
EXPERIMENTAL
IR spectra were registered on a spectrophotometer
Specord 75IR in mineral oil and chloroform. 1
H NMR
spectra were registered on a spectrometer Varian Unity
300 (300 MHz) in CDCl3, internal reference TMS.
Monitoring the reaction progress and checking the ho-
mogeneity of the synthesized compounds was performed
by TLC on plates withAl2O3 of the II grade Brockmann
activity (development in iodine vapor) in CH2Cl2 and on
Silufol UV-254 plates in CH2Cl2. Elemental analysis was
carried out on an analyzer Perkin Elmer 2400. Melting
points were measured in capillaries on a PTP instrument.
The benzoylation of furylnaphthooxazole Ia was
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ALEKSANDROV et al.
712
2-(2-Furyl)naphtho[1,2-d]oxazole (Ia). To a solution
extracted into dichloromethane and chromatographed on
a column packed with aluminum oxide eluting with di-
chloromethane. The solvent was evaporated, the residue
was recrystallized from 2-propanol. Yield 0.54 g (41%),
of 1.59 g (10 mmol) of 1-amino-2-hydroxynaphthalene
in 10 ml of 1-methyl-2-pyrrolidone was added 1.31 g
(10 mmol) of furoyl chloride. The mixture was boiled for
2 h, on cooling it was poured into 50 ml of cold water, the
separated precipitate was filtered off, thoroughly washed
with cold water, and crystallized from ethanol. Yield
mp 127–128°C. IR spectrum, ν, cm–1
: 1660 (C=O).
1H NMR spectrum, δ, ppm: 7.43 d (1H, H4’, J 3.5 Hz),
7.41 d (1H, H3’, J 3.5 Hz), 7.60 t (1H, H4, J 8.1 Hz),
7.71 t (1H, H8, J 8.1 Hz), 7.75 d (1H, H5, J 8.9 Hz),
7.89 d (1H, H4, J 9.0 Hz), 8.00 d (1H, H6, J 8.1 Hz),
8.59 d (1H, H9, J 8.2 Hz), 9.88 s (1H, CHO). Found,
%: C 72.88; H 3.57; N 5.05. C16H9NO3. Calculated, %:
C 73.00; H 3.45; N 5.32.
1
1.57 g (67%), mp 102– 103°C. H NMR spectrum, δ,
ppm: 6.64–6.66 m (1H, H4’), 7.30 d (1H, H3’, J 3.5 Hz,),
7.56 t (1H, H7, J 7.6 Hz), 7.67 t (1H, H8, J 8.2 Hz), 7.70
d (1H, H5’, J 1.8 Hz), 7.72 d (1H, H5, J 9.2 Hz), 7.82
d (1H, H4, J 8.9 Hz), 7.90 d (1H, H6, J 8.2 Hz), 8.60 d
(1H, H9, J 8.3 Hz). Found, %: C 76.43; H 4.12; N 6.07.
C15H9NO2. Calculated, %: C 76.59; H 3.86; N 5.95.
5-Nitro-2-(5-nitro-2-furyl)naphtho[1,2-d]-oxazole
(Ib). A solution of 1.18 g (5 mmol) of compound Ia in
25 ml of nitric acid (d 1.32 g/cm3) was boiled for 2 h.
The reaction mixture was cooled and poured into 100
ml of cold water. The separated precipitate was filtered
off, washed 2–3 times with a little cold water, and
crystallized from 2-propanol. Yield 0.99 g (61%), mp
199–200°C. IR spectrum, ν, cm–1: 1540 asym (NO2),
1370 sym (NO2). 1H NMR spectrum, δ, ppm: 7.52 d (1H,
H3’, J 3.9 Hz), 7.54 d (1H, H4’, J 3.9 Hz), 7.81 t (1H,
H7, J 8.1 Hz), 7.84 t (1H, H8, J 8.1 Hz), 8.54 s (1H, H5),
8.67–8.71 m (1H, H6), 8.64–8.67 m (1H, H9). Found,
%: C 55.67; H 2.48; N 13.17. C15H7N3O6. Calculated,
%: C 55.40; H 2.17; N 12.92.
2-(5-Acetyl-2-furyl)naphtho[1,2-d]oxazole (Ie).
To a solution of 1.18 g (5 mmol) of compound Ia
in 15 ml of acetic anhydride was added a catalytic
amount of anhydrone (magnesium perchlorate) [0.005 g
(0.02 mmol)], and the mixture was boiled for 1 h. Then
the reaction mixture was quenched with 25 ml of water
and neutralized with a concn. ammonia solution. The
reaction product was extracted into dichloromethane
and chromatographed on a column packed with alumi-
num oxide eluting with dichloromethane. The solvent
was evaporated, the residue was recrystallized from
2-propanol. Yield 1.08 g (78%), mp 128–129°C. IR
1
spectrum, ν, cm–1: 1680 (C=O). H NMR spectrum,
δ, ppm: 2.66 s (3H, CH3), 7.36 d (1H, H3’, J 3.8 Hz),
7.39 d (1H, H4’, J 3.8 Hz), 7.59 t (1H, H7, J 8.1 Hz),
7.70 t (1H, H8, J 8.1 Hz), 7.75 d (1H, H5, J 8.9 Hz),
7.88 d (1H, H4, J 8.9 Hz), 7.99 d (1H, H6, J 8.2 Hz),
8.58 d (1H, H9, J 8.2 Hz). Found, %: C 73.98; H 3.77;
N 4.92. C17H11NO3. Calculated, %: C 73.64; H 4.00;
N 5.05.
5-Bromo-2-(5-bromo-2-furyl)naphtho[1,2-d]oxa-
zole (Ic). To a solution of 1.18 g (5 mmol) of compound
Ia in 25 ml of dichloroethane was added 1.6 g (10 mmol)
of bromine, and the mixture was boiled for 4 h, the
solvent was evaporated in air, the residue was crystal-
lized from alcohol. Yield 1.30 g (66%), mp 141–142°C.
1H NMR spectrum, δ, ppm: 6.66 d (1H, H4’, J 3.5 Hz),
7.28 d (1H, H3’, J 3.5 Hz), 7.56 t (1H, H7, J 7.6 Hz),
7.67 t (1H, H8, J 8.2 Hz), 8.05 d (1H, H6, J 8.2 Hz),
8.12 s (1H, H4), 8.60 d (1H, H9, J 8.2 Hz). Found, %:
C 46.12; H 2.13; N 3.17. C15H7Br2NO2. Calculated, %:
C 45.84; H 1.80; N 3.56.
2-(5-Benzoyl-2-furyl)naphtho[1,2-d]oxazole (If).
A mixture of 1.18 g (5 mmol) of compound Ia, 20 g of
polyphosphoric acid, and 1.8 g (15 mmol) of benzoic
acid was heated with stirring for 12 h at 140–150°C. The
reaction product was isolated like the acetyl derivative
Ie. Yield 0.73 g (43%), mp 105–106°C (from alcohol).
IR spectrum, ν, cm–1: 1640 (C=O). 1H NMR spectrum,
δ, ppm: 7.37 d (1H, H3’, J 3.5 Hz), 7.40 d (1H, H4’,
J 3.5 Hz), 7.56 t (3H, H3,4,5arom, J 7.7 Hz), 7.60 t (1H,
H7, J 8.1 Hz), 7.70 t (1H, H8, J 8.1 Hz), 7.75 d (1H,
H5, J 8.9 Hz), 7.88 d (1H, H4, J 8.9 Hz), 7.99 d (1H,
H6, J 8.2 Hz), 8.10 d (2H, H2,6arom, J 7.8 Hz), 8.60 d
(1H, H9, J 8.2 Hz). Found, %: C 78.13; H 4.15; N 3.88.
C22H13NO3. Calculated, %: C 77.87; H 3.86; N 4.13.
2-(5-Formyl-2-furyl)naphtho[1,2-d]oxazole (Id).
To a mixture of 1.18 g (5 mmol) of compound Ia and
20 g of polyphosphoric acid was added 2.8 g (20 mmol)
of urotropin, the reaction mixture was heated for 4 h
at 80–90°C while vigorous stirring. Then the reaction
mixture was diluted with 50 ml of water and neutral-
ized with ammonia solution. The reaction product was
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SYNTHESIS AND SOME TRANSFORMATIONS OF 2-(2-FURYL)NAPHTHO[1,2-d]OXAZOLE
713
Khim. Geterotsikl. Soedin., 1979, p. 1047.
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