Synthesis and reactivity of 2-(furan-2-yl)benzo[e][1,3]benzothiazole

Article abstract of DOI:10.1134/S1070363217080138

N-(1-Naphthyl)furan-2-carboxamide was synthesized by the coupling of naphthalen-1-amine with furan-2-carbonyl chloride in propan-2-ol and then treated with excess P2S5 in anhydrous toluene to obtain the corresponding thioamide. The latter was oxidized wit

Full text of DOI:10.1134/S1070363217080138

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 8, pp. 1716–1720. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © А.А. Aleksandrov, М.М. El’chaninov, 2017, published in Zhurnal Obshchei Khimii, 2017, Vol. 87, No. 8, pp. 1304–1308.
Synthesis and Reactivity
of 2-(Furan-2-yl)benzo[e][1,3]benzothiazole
А. А. Aleksandrov* and М. М. El’chaninov
Platov South-Russian State Polytechnic University, pr. Prosveshcheniya 132, Novocherkassk, 346428 Russia
*е-mail: aaanet1@yandex.ru
Received May 29, 2017
Abstract—N-(1-Naphthyl)furan-2-carboxamide was synthesized by the coupling of naphthalen-1-amine with
furan-2-carbonyl chloride in propan-2-ol and then treated with excess P2S5 in anhydrous toluene to obtain the
corresponding thioamide. The latter was oxidized with potassium ferricyanide in an alkaline medium by the
Jakobson procedure to synthesize 2-(furan-2-yl)benzo[e][1,3]benzothiazole which was subjected to
electrophilic substitution reactions: nitration, bromination, formylation, and acylation.
Keywords: naphthalen-1-amine, furan-2-carbonyl chloride, N-(1-naphthyl)furan-2-carboxamide, potassium
ferricyanide, 2-(furan-2-yl)benzo[e][1,3]benzothiazole, electrophilic substitution reactions
DOI: 10.1134/S1070363217080138
Among of a great variety of heterocyclic systems
which have been vigorously and successfully studied
over the past years, bishetaryls belong to a rather
numerous family of compounds which present interest
but still are poorly understood. Bishetaryls comprise
heterocyclic nuclei of different nature, whose interac-
tion sometimes have an unexpected impact on the reac-
tivity of such compounds. This also relates to 2-hetaryl-
substituted thiazoles, many of which were shown to
exhibit biological activity [1, 2].
We first prepared 2-(furan-2-yl)benzo[e][1,3]benzo-
thiazole 1 by the Jakobson synthesis [5], which
involves cyclization of thioamino benzene derivatives
in aqueous solutions of alkalis in the presence of
potassium ferricyanide. The starting N-(1-naphthyl)-
furan-2-carboxamide 3 was prepared in 73% yield by
refluxing naphthalen-1-amine with furan-2-carbonyl
chloride in propan-2-ol. By heating compound 3 with
excess phosphorus pentasulfide in anhydrous toluene
we could replace the carbonyl oxygen by sulfur to
obtain N-(1-naphthyl)furan-2-carbothioamide 4 in 59%
yield (Scheme 2). The oxidation of compound 4 with
20% aqueous K3[Fe(CN)6] gave 2-(furan-2-yl)benzo[e]-
[1,3]benzothiazole 1 in 34% yield (Scheme 3).
Furyl-substituted benzo[e][1,3]benzothiazole 1 has
scarcely been reported in the literature. In this
connection we set ourselves the goal to develop a
convenient synthetic approach to this compound, as
well as to assess its reactivity and compare it with the
reactivity of the previously studied naphthoimizole
analog 2 [3, 4] (Scheme 1).
The composition and structure of the synthesized
compounds were confirmed by NMR spectroscopy and
1
elemental analysis (Tables 1 and 2). The H NMR
Scheme 1.
N
N
O
N
S
O
CH3
2
1
1716

SYNTHESIS AND REACTIVITY OF 2-(FURAN-2-YL)BENZO[e][1,3]BENZOTHIAZOLE
1717
Scheme 2.
P2S5
H O
N
H
N
S
O
O
3
4
Scheme 3.
K3[Fe(CN)6]
KOH
H
N
S
N
O
O
S
1
4
spectrum of compound 1 displays the naphthalene Н4,5
proton signals as doublets at 7.79 and 7.70 ppm with
characteristic coupling constants of 9.0 and 8.9 Hz.
This findings provides evidence for the 1,2-fusion of
the 2-(furan-2-yl)thiazole moiety to naphthalene.
suggest a lower relative reactivity of the furan ring in
the former compound.
Evidence for this suggestion was provided by the
results of the above-mentioned reactions. Thus, the
attempted nitration of compound 1 with a complex
Cu(NO3)2 and acetic anhydride resulted in an almost
complete recovery of the starting compound, whereas
compound 2 under same conditions gave a 5,5-dinitro
derivative by the furan and naphthalene rings.
Successful nitration could only be accomplished by
heating compound 1 in dilute nitric acid (d = 1.32 g/cm3).
The reactivity assessment of compound 1 was
performed by its treatment with electrophilic agents,
sucg as acetyl nitrate and nitric acid, bromine, sulfuric
acid, urotropine, acetic anhydride, and benzoic acid
1
(Scheme 4). Analysis of the Н NMR spectra of
compounds 1 and 2 revealed a clear correlation
between the downfield shifts of the furan Н3 proton
signals (7.30 and 7.15 ppm), associated first of all with
the inductive effect and the electron-acceptor power of
the naphthothiazole or imidazole substituents, which is
weaker in the latter case. This fact can be explained by
that the pyrrole heteroatom in the naphthothiazole
fragment of compound 1, unlike that in imidazole 2,
exhibits acceptor properties, and, therefore, one can
1
According to the Н NMR data, nitration involved
exclusively the furan ring to form 5-nitro derivative 5.
An analogous result was obtained after the bromine-
tion of naphthothiazole 1 in dichloroethane under
reflux. The yield of 2-(5-bromofuran-2-yl)benzo[e]-
[1,3]benzothiazole 6 was 66%. Compound 2 formed
dibromo derivative already at –5°С [3], while com-
pound 1 did not react under these conditions.
Table 1. Melting point, elemental analyses, and yields of compounds 1–9а
Found, %
Calculated, %
H
Comp.
no.
Yield, %
mp, °С
Formula
С
Н
N
C
N
3
4
1
5
6
7
8
9
73
59
34
53
62
59
37
45
148–149
117–118
74–76
76.22
70.89
71.41
61.03
54.47
69.03
69.77
74.22
4.55
4.42
3.83
2.56
2.59
3.47
3.56
3.45
6.17
5.77
5.81
9.27
3.98
4.79
5.03
4.17
С15Н11NO2
С15Н11NОS
С15Н9NОS
75.94
71.12
71.69
60.80
54.56
68.80
69.61
74.35
4.67
4.38
3.61
2.72
2.44
3.25
3.78
3.69
5.90
5.53
5.57
9.45
4.24
5.01
4.77
3.94
221–223
156–157
144–145
133–134
154–155
С15Н8N2O3S
С15Н8BrNОS
С16Н9NO2S
С17Н11NO2S
С22Н13NO2S
a The results of elemental analysis for С, Н, and N agree with calculation within ±0.34%.
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ALEKSANDROV, EL’CHANINOV
Table 2. IR and 1Н NMR (CDCl3) data for compounds 1–9
Comp.
ν, сm–1
no.
δ, ppm (J, Hz)
3
4
1
5
6
7
8
9
1685 s (С=О), 6.59–6.61 m (1Н, Н4furan), 7.29 d (1Н, Н3furan, J = 3.6), 7.51 t (2Н, Н6,7Ar, J = 7.8), 7.53 t (1Н, Н3
3313 br (NH) J = 7.8), 7.58 d (1Н, Н5furan, J = 1.5), 7.72 d (1Н, Н5Ar, J = 8.4), 7.88 d (1Н, Н2Ar, J = 8.4), 7.94 d
(1Н, Н4Ar, J = 8.1), 8.13 d (1Н, Н8Ar, J = 7.5), 8.54 s (1Н, NH)
1235 s (С=S), 6.57–6.59 m (1Н, Н4furan), 7.30 d (1Н, Н3furan, J = 3.6), 7.48 t (2Н, Н6,7Ar, J = 7.6), 7.52 t (1Н, Н3
3341 br (NН) J = 7.8), 7.58 d (1Н, Н5furan, J = 1.5), 7.71 d (1Н, Н5Ar, J = 8.2), 7.86 d (1Н, Н2Ar, J = 8.4), 7.93 d
(1Н, Н4Ar, J = 8.2), 8.15 d (1Н, Н8Ar, J = 7.5), 11.28 s (1Н, NH)
,
Ar
,
Ar
–
6.60–6.62 m (1Н, Н4furan), 7.23 d (1Н, Н3furan, J = 3.6), 7.57 t (1Н, Н7Ar, J = 8.4), 7.60 d (1Н,
Н5furan, J = 0.9), 7.67 t (1Н, Н8Ar, J = 7.2), 7.79 d (1Н, Н5Ar, J = 8.7), 7.89 d (1Н, Н4Ar, J = 8.9),
7.94 d (1Н, Н6Ar, J = 8.1), 8.86 d (1Н, Н9Ar, J = 8.1)
1543 [νas(NO2)], 7.50 d (1Н, Н3furan, J = 3.9), 7.52 d (1Н, Н4furan, J = 3.9), 7.62 t (1Н, Н7Ar, J = 7.8), 7.75 t (1Н,
1385 [νs(NO2)] Н8Ar, J = 7.8), 7.87 d (1Н, Н5Ar, J = 9.0), 7.92 d (1Н, Н4Ar, J = 9.0), 7.98 d (1Н, Н6Ar, J = 8.2),
8.82 d (1Н, Н9Ar, J = 8.1)
–
6.53 d (1Н, Н4furan, J = 3.6), 7.19 d (1Н, Н3furan, J = 3.6), 7.57 t (1Н, Н7Ar, J = 8.1), 7.67 t (1Н,
Н8Ar, J = 8.1), 7.79 d (1Н, Н5Ar, J = 8.2), 7.89 s (1Н, Н4Ar, J = 9.0), 7.93 d (1Н, Н6Ar, J = 7.8),
8.86 d (1Н, Н9Ar, J = 8.4)
1658 s (С=О) 7.39 d (1Н, Н4furan, J = 3.9), 7.41 d (1Н, Н4furan, J = 3.9), 7.61 t (1Н, Н7Ar, J = 7.5), 7.70 t (1Н,
Н8Ar, J = 7.8), 7.85 d (1Н, Н5Ar, J = 9.0), 7.93 d (1Н, Н4Ar, J = 9.0), 7.96 d (1Н, Н6Ar, J = 8.4),
8.85 d (1Н, Н9Ar, J = 8.1), 9.77 s (1Н, СНО)
1678 s (С=О) 2.65 s (3Н, СН3), 7.35 d (1Н, Н3furan, J = 3.8), 7.39 d (1Н, Н4furan, J = 3.8), 7.59 t (1Н, Н7Ar, J =
8.0), 7.68 t (1Н, Н8Ar, J = 8.1), 7.71 d (1Н, Н5Ar, J = 9.0), 7.85 d (1Н, Н4Ar, J = 9.0), 7.96 d (1Н,
Н6Ar, J = 8.2), 8.55 d (1Н, Н9Ar, J = 8.2)
1665 s (С=О) 7.41 d (1Н, Н4furan, J = 3.5), 7.44 d (1Н, Н3furan, J = 3.5), 7.53 t (1Н, Н3,4,5Ar, J = 7.7), 7.57 t (1Н,
Н7Ar, J = 7.5), 7.63 t (1Н, Н8Ar, J = 7.5), 7.84 d (1Н, Н5Ar, J = 8.7), 7.93 d (1Н, Н4Ar, J = 8.7), 7.96
d (1Н, Н6Ar, J = 8.7), 8.07 d (1Н, Н2,6Ar, J = 8.1), 8.86 d (1Н, Н9Ar, J = 8.4)
Five-membered π-excessive heterocycles and their
derivatives are presently successfully formylated by
the Vilsmeier reaction. However, according to [6], this
method not infrequently fails with hetarylimidazoles.
Compound 1, too, did not react with the DMF–POCl3
complex, but could be formylated with urotropine in
polyphosphoric acid at 90–100°С (Scheme 3). The
yield of aldehyde 7 was as low as 59%. The rest of the
starting compound was consumed to form by-products
which we failed to isolate and identify. Under the same
conditions, compound 2 reacted already at 60°С to
form a 5-formylfuran derivative in 75% yield.
this case compound 1 is likely to be acetylated in the
basic form, where the electron-acceptor power of the
naphthothiazole moiety is much lower. The reaction is
also facilitated by quite a low basicity of the latter [8].
The yield of 5-acetyl derivative 8 proved to be as low
as 37% (Scheme 4).
Benzylation of furylnaphthothiazole 1 was per-
formed under the action of benzoic acid in poly-
phosphoric acid at 140°С. Unlike what was observed
with compound 2, the reaction of compound 1 pro-
ceeded with great difficulty and provided a low yield
of ketone 9 (Scheme 3). By contrast, compound 2
formed its 5-benzoyl derivative within 4–6 h in 70%
yield, whereas the yield of [5-(benzo[e][1,3]benzothia-
zol-2-yl)furan-2-yl](phenyl)methanone 9 within 12 h
was not higher than 45%, and, therewith, 43% of the
starting compound was recovered.
According to published data [3], compound 2 was
acetylated by treatment with acetic anhydride at 100–
110°С in polyphosphoric acid. Interestingly, we could
acetylate compound 1 in boiling acetic anhydride in
the presence of catalytic amounts of anhydrone, i.e.
under the conditions of the Dorofeenko reaction [7]. In
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SYNTHESIS AND REACTIVITY OF 2-(FURAN-2-YL)BENZO[e][1,3]BENZOTHIAZOLE
1719
Scheme 4.
N
O
PhCOOH, PPA
or
(СH2)6N4, PPA
S
1
HNO3
Br2,
Ac2O
1,2-dichloroethane
R
R
O
N
N
O
O
S
S
7_9
5, 6
R = NO2 (5), Br (6), Н (7), Ме (8), Ph (9).
Thus, 1,2-fusion of the 2-(furan-2-yl)thiazole moiety
to naphthalene was performed for the first time. The
relative reactivity of the synthesized 2-(furan-2-yl)-
benzo[e][1,3]benzothiazole with respect to electro-
philic agents was studied.
20 mL of anhydrous toluene. The mixture was refluxed
for 3 h, and toluene was then removed by distillation.
The precipitate was recrystallized from aqueous
propan-2-ol. Yield 5.23 g, yellow crystals.
2-(Furan-2-yl)benzo[e][1,3]benzothiazole (1). To
a solution of 5.07 g (0.020 mol) of compound 4 in
10 mL of propan-2-ol, 15 mL of 2% KOH was added,
after which 50 mL of a warm aqueous solution of
19.74 g (0.060 mol) of K3[Fe(CN)6] was gradually
added. The mixture was thoroughly mixed and left to
stand overnight at room temperature. The precipitate
was separated and recrystallized from aqueous alcohol.
Yield 1.71 g, colorless crystals.
EXPERIMENTAL
The IR spectra were registered on a Specord 75IR
spectrometer in mineral oil. The 1Н NMR spectra were
measured on
a
Varian Unity 300 instrument
(300 MHz, CDCl3) against internal TMS. The reaction
progress was monitored by TLC on Al2O3 plates
(Brockmann activity grade II), eluents CH2Cl2 and
CHCl3, development in iodine vapor. Elemental
analysis was performed on a Perkin Elmer 2400
analyzer. The melting points were determined using
capillaries in a PTP apparatus.
2-(5-Nitrofuran-2-yl)benzo[e][1,3]benzothiazole
(5). A mixture of 0.251 g (1 mmol) of compound 1 and
5 mL of nitric acid (d = 1.32 g/cm3) was stirred at 80°С
for 3 h and then poured into 100 mL of cold water. The
precipitate was separated, washed with 2–3 small
portions of cold water, and recrystallized from propan-
2-ol. Yield 0.16 g, yellow crystals.
The physicochemical and spectral characteristics of
the synthesized compounds are listed in Tables 1 and 2.
N-(1-Naphthyl)furan-2-carboxamide (3). Furan-2-
carbonyl chloride, 6.53 g (0.05 mol), was added to a
solution of 7.15 g (0.05 mol) of naphthalene-1-amine
in 50 mL of propan-2-ol. The mixture was refluxed for
2 h, poured into 50 mL of water, made weakly alkaline
with ammonia solution, and left to stand in a
refrigerator for 24 h. The precipitate was filtered off
and recrystallized from propan-2-ol. Yield 8.65 g, cream
crystals.
2-(5-Bromofuran-2-yl)benzo[e][1,3]benzothiazole
(6). Bromine, 0.32 g (2 mmol), was added to a solution
of 0.251 g (1 mmol) of compound 1 in 10 mL of
dichloroethane. The mixture was refluxed for 4 h, and
then solvent was removed. The residue was neutralized
with ammonia solution. The precipitate was filtered off
and recrystallized from aqueous propan-2-ol. Yield
0.20 g, cream crystals.
N-(1-Naphthyl)furan-2-carbothioamide (4). Phos-
phorus pentasulfide, 4.44 g (0.020 mol), was added to
a solution of 8.30 g (0.035 mol) of compound 3 in
5-(Benzo[e][1,3]benzothiazol-2-yl)furan-2-carbal-
dehyde (7). A mixture of 0.251 g (1 mmol) of com-
pound 1 and 0.42 g (3 mmol) of urotropine in 5 g of
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ALEKSANDROV, EL’CHANINOV
polyphosphoric acid was stirred at 110–120°С for 6 h,
diluted with 10 mL of water, and neutralized with
caution with ammonia solution. The product was
extracted with 15 mL of chloroform and subjected to
column chromatography on alumina, eluent chloro-
form. Compound 7 was crystallized from ethanol.
Yield 0.16 g, yellow crystals.
crystallized from n-propanol. Yield 0.149 g, yellow
crystals.
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1-[5-(Benzo[e][1,3]benzothiazole-2-yl)furan-2-yl]-
ethanone (8). Anhydrone (magnesium perchlorate),
0.005 g (0.02 mmol), was added to a solution of
0.251 g (1 mmol) of compound 1 in 3 mL of acetic
anhydride. The mixture was refluxed for 3 h and then
decomposed with 10 mL of water and neutralized with
concentrated ammonia. The product was extracted
with 15 mL of chloroform and subjected to column
chromatography on alumina, eluent chloroform. Yield
0.105 g, yellow crystals.
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[5-(Benzo[e][1,3]benzothiazol-2-yl)furan-2-yl]-
(phenyl)methanone (9). A mixture of 0.251 g
(1 mmol) of compound 1 and 0.37 g (3 mmol) of
benzoic acid in 5 g of polyphosphoric acid was stirred
for 10 h at 130–140°С. Further workup was performed
as described for compound 7. Compound 9 was re-
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