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

Article abstract of DOI:10.1134/S1070363214040136

Condensation of 1-amino-2-hydroxynaphthalene with thenoyl chloride in 1-methyl-2-pyrrolidinone medium afforded 2-(2-thienyl)naphtho[1,2-d]oxazole. The latter was brought into electrophilic substitution reactions like nitration, bromination, sulfonation, f

Full text of DOI:10.1134/S1070363214040136

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 4, pp. 682–685. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © A.A. Aleksandrov, E.V. Illenzeer, M.M. El’chaninov, 2014, published in Zhurnal Obshchei Khimii, 2014, Vol. 84, No. 4, pp. 602–
606.
Synthesis and Some Transformations
of 2-(2-Thienyl)naphtho[1,2-d]oxazole
A. A. Aleksandrov, E. V. Illenzeer, and M. M. El’chaninov
Platov Southern Russian State Polytechnic University (Novocherkassk Polytechnic Institute),
pr. Prosveshcheniya 132, Novocherkassk, 346428 Russia
e-mail: aaanet1@yandex.ru
Received July 4, 2013
Abstract―Condensation of 1-amino-2-hydroxynaphthalene with thenoyl chloride in 1-methyl-2-pyrrolidinone
medium afforded 2-(2-thienyl)naphtho[1,2-d]oxazole. The latter was brought into electrophilic substitution
reactions like nitration, bromination, sulfonation, formylation, and acylation. The reactions proceeded via
electrophilic attack at the 5-position of the thiophene ring, but the nitration and bromination occurred involving
both the thiophene and naphthalene fragments.
Keywords: naphthooxazoles, reactivity, electrophilic substitution, bihetaryl compounds
DOI: 10.1134/S1070363214040136
Mutual influence of heterocyclic scaffolds in bi-
hetaryl compounds is an interesting and still
insufficiently explored problem. Data on the reactivity
of compounds in which naphthooxazole and π- exces-
sive thiophene rings are linked to each other by a
single bond are scarce. Sometimes the reactivity of
these substances is quite unexpected. Thus, for
example, the formylation of 2-(2-thienyl)oxazole oc-
curred involving oxazole ring, although thiophene ring
is more π-excessive [1].
actions like nitration, bromination, sulfonation, formyla-
tion, and acylation (Table 1).
Cl
S
NH2
O
N
O
S
OH
The comparison of chemical shifts of the protons of
2-thienyl group of compounds I, II [2] shows that their
H4 protons are the most shielded (7.19 and 7.20 ppm).
This insensitivity of the protons in the meta-position
relative to the substituent is typical for all π-conjugated
systems. The protons H5 (7.53 and 7.51 ppm) and H3
The aim of this work was the synthesis of 2-(2-
thienyl)naphtho[1,2-d]oxazole I and the study of its
relative reactivity in comparison with naphthoimida-
zole analog II [2].
1
(7.93 and 7.57 ppm) are deshielded. Therefore, H
NMR spectroscopy data show a clear correlation
between the downfield shift of the protons H3 of the
thiophene ring caused primarily by the inductive effect
and electron-acceptor effect of naphthooxazole or
naphthoimidazole moieties, which is lower in the latter
case. So, a decrease in the relative reactivity of the
thiophene ring in compound I is expectable.
N
O
S
N
S
N
I
II
The reactions performed confirm this assumption.
For example, the nitration of I with Cu(NO3)2 in the
presence of acetic anhydride did not occur, while the
nitration of compound II under these conditions
proceeded involving the naphthalene ring to afford a 5-
Compound I we obtained for the first time via
condensation of 1-amino-2-hydroxynaphthalene with
thenoyl chloride in 1-methyl-2-pyrrolidinone medium
in 63% yield. 2-(2-Thienyl)naphtho[1,2-d]oxazole I
obtained was brought into electrophilic substitution re-
682

SYNTHESIS AND SOME TRANSFORMATIONS
683
Table 1. Melting points, elemental analysis data, and yields of the compounds obtained
Found, %
Calculated, %
H
Comp. Yield,
mp, °С
Formula
%
no.
С
Н
N
C
N
I
63
67
42
53
23
18
37
131–132
179–180
180–181
203–204
203–204
166–167
154–155
71.35
53.03
54.89
43.79
69.17
69.37
74.69
3.77
1.95
2.57
2.03
3.49
4.03
3.37
5.83
12.44
C15H9NOS
71.69
52.79
54.56
44.04
69.80
69.61
74.35
6.31
2.07
5.57
12.31
IIIа
IIIb
IIIc
IIId
IIIe
IIIf
C15H7N3O5S
C15H8BrNOS
C15H7Br2NOS
C16H9NO2S
C17H11NO2S
C22H13NO2S
Br 23.93
Br 38.78
4.88
2.44
1.72
3.25
3.78
3.69
Br 24.20
Br 39.06
5.01
5.0.9
4.77
4.28
3.94
nitro derivative [2]. Refluxing of compound I in
diluted nitric acid (d = 1.32 g cm–3) resulted in 5,5-
dinitro derivative IIIa.
sulfuric acid in polyphosphoric acid (PPA) proceeds,
but the sulfonic acid obtained undergoes desulfonation
when the reaction is quenched with water. Apparently,
in this case the sulfonic acid can exist only as a
zwitterion, whose stability depends on the basicity of
naphthooxazole fragment, and it is known to be the
lowest among the azoles [3].
The bromination of naphthooxazole I with 1 equiv
of bromine under reflux in dichloromethane occurred
involving thiophene ring to afford 5-bromo derivative
IIIb in 42% yield; additionally, 37% of I was
recovered. When 3 equiv of bromine was used, both
the thiophene and naphthalene moieties undergo bromina-
tion to give a mixture of mono- (IIIb) and dibromo
derivatives (IIIc) isolated by column chromatography.
Compound II yielded analogous dibromo derivative
already at –5°C [2], while compound I does not
undergo conversion under these conditions (Scheme 1).
Since formylation of compound I with the
Vilsmeier reagent had failed, in this work we
performed formylation by heating a mixture of I with
hexamethylenetetramine in polyphosphoric acid medium
at 90–100°C, a procedure previously successfully used
for the formylation of 2-(2-hetaryl)benzimidazoles.
Compared with naphthoimidazole II affording 5-
formyl derivative in 75% yield [2], the corresponding
2-(5-formyl-2-thienyl)naphtho[1,2-d]oxazole IIId was
obtained in ~23% yield along with recovered
compound I and unidentified impurity (64%, Table 2).
As in the case of compound II, we failed to isolated
any sulfo derivative of 2-(2- thienyl)naphtho[1,2-d]
oxazole I. According to TLC, the reaction of I with
Scheme 1.
R1
HNO3 or Br2,
dichloroethane
N
S
N
O
S
_HBr
R2
O
IIIа_IIIc
I
O
RCOOH or
(CH2)6N4, PPA
R1
N
S
_H2O, _CH2O
O
IIId_IIIf
R1 = R2 = NO2 (а); R1 = Br, R2 = H (b); R1 = R2 = Br (c); R1 = H (d); R1 = Me (e); R1 = Ph (f).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 4 2014

684
ALEKSANDROV et al.
Table 2. Spectral parameters of compounds obtained
Comp. IR spectrum,
1Н NMR spectrum, δ, ppm (J, Hz)
no.
ν, cm–1
–
7.19 t (1Н, Н4', J 4.5), 7.52 t (1Н, Н7, J 8.2), 7.53 d (1Н, Н5', J 5.1), 7.64 t (1Н, Н8, J 8.2), 7.68 d (1Н,
Н5, J 8.7), 7.78 d (1Н, Н4, J 8.7), 7.93 d (1Н, Н3', J 3.9), 7.95 d (1Н, Н6, J 7.5), 8.54 d (1Н, Н9, J 8.1)
I
1370 s (NO2) 7.81 t (1Н, Н7, J 8.1), 7.85 t (1Н, Н8, J 8.1), 7.92 d (1Н, Н4', J 4.5), 8.02 d (1Н, Н3', J 4.5), 8.55 s (1Н,
Н4), 8.66–8.68 m (1Н, Н9), 8.69 d (1Н, Н6, J 7.5)
1550 as (NO2) 7.16 d (1Н, Н4', J 3.9), 7.50 t (1Н, Н7, J 8.0), 7.62 t (1Н, Н8, J 8.2), 7.65 d (1Н, Н5, J 8.5), 7.67 d (1Н,
Н3', J 3.9), 7.75 d (1Н, Н4, J 8.5), 7.98 d (1Н, Н6, J 7.5), 8.52 d (1Н, Н9, J 8.0)
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
–
7.16 d (1Н, Н4', J 3.9), 7.65 d (1Н, Н3', J 3.9), 7.66 t (1Н, Н7, J 8.1), 7.71 t (1Н, Н8, J 8.0), 8.04 s (1Н,
Н4), 8.34 d (1Н, Н6, J 7.5), 8.53 d (1Н, Н9, J 8.1)
–
7.58 t (1Н, Н7, J 8.4), 7.70 t (1Н, Н8, J 8.0), 7.72 d (1Н, Н5, J 9.0), 7.82 d (1Н, Н4', J 3.9), 7.86 d (1Н,
Н4, J 9.0), 7.98 d (1Н, Н6, J 8.0), 7.99 d (1Н, Н3', J 3.9), 8.56 d (1Н, Н9, J 8.4), 10.00 s (1H, CHO)
1680 (С=О) 2.63 s (3H, CH3), 7.57 t (1Н, Н7, J 8.2), 7.69 t (1Н, Н8, J 8.1), 7.70 d (1Н, Н5, J 9.0), 7.72 d (1Н, Н4',
J 4.2), 7.84 d (1Н, Н4, J 9.0), 7.92 d (1Н, Н3', J 4.2), 7.97 d (1Н, Н6, J 8.0), 8.56 d (1Н, Н9, J 8.1)
1670 (С=О) 7.55 t (1Н, Н7, J 8.2), 7.67 t (1Н, Н8, J 8.1), 7.70 d (1Н, Н5, J 9.0), 7.70–7.75 m (3Н, Н3'',4'',5''), 7.72 d
(1Н, Н4', J 4.2), 7.86 d (1Н, Н4, J 9.0), 7.93 d (2Н, Н2'',6'', J 7.5), 7.96 d (1Н, Н3', J 4.2), 7.98 d (1Н, Н6,
1640 (С=О) J 8.0), 8.57 d (1Н, Н9, J 8.1)
Acylation of compound I by various methods was
EXPERIMENTAL
unsuccessful. Recently compound II has been acylated
similarly to acylation of phenols and phenyl ethers by
the action of acetic acid or anhydride in
polyphosphoric acid at 110–120°C [4]. Therefore we
applied this method for acylation of compound I.
Acylation of naphthooxazole I occurred slowly to give
in 28 h ketone IIIe in 18% yield, while compound II
transformed into a similar ketone in 55% yield within
6 h.
IR spectra were recorded in chloroform solutions
on a Specord IR-75 spectrometer. H NMR spectra
1
were taken on a Varian Unity-300 spectrometer
(300 MHz) using the residual proton signals of CDCl3
as internal reference (δ = 7.26 ppm). Elemental analysis
was performed on a Perkin-Elmer 2400 analyzer.
Melting points were determined by the capillary
method on a PTP instrument. The reaction progress
was monitored by TLC using plates coated with Al2O3
or Silufol UV-254 plates, eluting with CH2Cl2 and
detecting with iodine vapor. Yields, melting points,
elemental analysis data, and spectral characteristics of
the compounds obtained are reported in Tables 1 and 2.
Benzoylation of thienylnaphthooxazole I was
performed by the Gardner method by the action of
benzoic acid in polyphosphoric acid medium at 160°C.
Unlike compound II, the reaction proceeded with great
difficulties to give ketone IIIf in 37% yield within 15
h. In addition, 47% of recovered compound I was
obtained. For comparison, compound II was converted
into 5-benzoyl derivative in 4–6 h in 56% yield.
2-(2-Thienyl)naphtho[1,2-d]oxazole (I). To
a
solution of 1.59 g (10 mmol) of 1-amino-2-hydroxy-
naphthalene in 10 mL of 1-methyl-2-pyrrolidone was
added 1.44 g (10 mmol) of thenoyl chloride. The
mixture was refluxed for 2 h, then cooled and poured
into 50 mL of cold water. The precipitate was
separated, washed thoroughly with ethanol, and
recrystallized to yield colorless needles.
In summary, it may be concluded that the reactions
of electrophilic substitution of 2-(2-thienyl)naphtho-
[1,2-d]oxazole proceeded with greater difficulty than
in the case of 1-methyl-2-(2-thienyl)-1H-naphtho-
[1,2-d]imidazole. The experimental data confirm
higher deshielding (electron-withdrawing) effect of
naphtho[1,2-d]oxazol-2-yl group compared with
naphtho[1,2-d]imidazole moiety.
5-Nitro-2-(5-nitro-2-thienyl)naphtho[1,2-d]oxazole
(IIIa). A solution of 1.26 g (5 mmol ) of compound I
in 25 mL of nitric acid (d = 1.32 g cm–3) was refluxed
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SYNTHESIS AND SOME TRANSFORMATIONS
685
for 2 h. After cooling the reaction mixture was poured
into 100 mL of cold water. The precipitate was filtered
off, washed 2–3 times with cold water, and recrystal-
lized from propan-2-ol to yield yellow crystals.
chloride. The extract was dried over anhydrous
Na2SO4 and chromatographed on a column filled with
Al2O3 eluting with methylene chloride. Recrystal-
lization from alcohol afforded yellow crystals.
2-(5-Bromo-2-thienyl)naphtho[1,2-d]oxazole (IIIb).
To a solution of 1.26 g (5 mmol) of compound I in
25 mL of dichloroethane was added 0.8 g (5 mmol) of
bromine. The mixture was refluxed for 6 h. Then the
solvent was evaporated in air. The residue was
dissolved in methylene chloride and chromatographed
on Al2O3, eluting with methylene chloride. Recrystalliza-
tion from alcohol afforded needle crystals.
2-(5-Acetyl-2-thienyl)naphtho[1,2-d]oxazole (IIIe).
To a solution of 1.26 g (5 mmol) of compound I in
20 g of polyphosphoric acid was added 0.95 mL
(10 mmol) of acetic anhydride. The resulting mixture
was heated for 28 h at 110–120°C under stirring. The
reaction mixture was poured into 100 mL of water,
neutralized with ammonia solution, and then the
reaction product was isolated similarly to IIId. Re-
crystallization from alcohol afforded yellow crystals.
5-Bromo-2-(5-bromo-2-thienyl)naphtho[1,2-d]-
oxazole (IIIc). To a solution of 1.26 g (5 mmol) of
compound I in 25 mL of dichloroethane was added
2.4 g (15 mmol) of bromine. The mixture was refluxed
for 4 h and then poured into a Petri dish. After
dichloroethane evaporation the residue was dissolved
in CH2Cl2 and chromatographed on a column filled
with Al2O3, eluting with methylene chloride. Recrys-
tallization from alcohol afforded needle crystals.
2-(5-Benzoyl-2-thienyl)naphtho[1,2-d]oxazole (IIIf).
A mixture of 1.26 g (5 mmol) of compound I, 20 g of
polyphosphoric acid, and 2.44 g (20 mmol) of benzoic
acid was heated at 140–150°C for 15 h. The reaction
product was isolated similarly to IIId. Recrystal-
lization from alcohol afforded pale brown crystals.
REFERENCES
1. Belen’kii, L.I., Cheskis, M.A., Zvolinskii, V.P., and
Obukhov, A.E., Chem. Heterocycl. Comp., 1986, vol. 22,
no. 6, p. 650.
2-(5-Formyl-2-thienyl)naphtho[1,2-d]oxazole
(IIId). To a mixture of 1.26 g (5 mmol) of compound I
in 20 g of polyphosphoric acid was added 2.8 g
(20 mmol) of hexamethylenetetramine. The mixture
was heated for 6 h at 90–100°C with vigorous stirring.
Then the reaction mixture was diluted with 50 mL of
water and neutralized with ammonia under cooling.
The reaction product was extracted with methylene
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