Syntheses and reactions of halo- and arylazo-substituted 3-(3-(2-naphthyl)acryloyl)tropolones: Formation of (naphthalen-2-yl)vinyl- substituted heterocycle-fused troponoid compounds

Article abstract of DOI:10.1002/jhet.243

(Chemical Equation Presented) The starting substrate 3-(3-(2-naphthyl) acryloyl)tropolone (1) was achieved by the aldol condensation reaction of 3-acetyltropolone with 2-naphthaldehyde. Compound (1) reacted with bromine to give 7-bromo-(2) and 5,7-dibromo

Full text of DOI:10.1002/jhet.243

1302
Syntheses and Reactions of Halo- and Arylazo-Substituted
3-(3-(2-Naphthyl)acryloyl)tropolones: Formation of (Naphthalen-
2-yl)Vinyl)-Substituted Heterocycle-Fused Troponoid Compounds
Vol 46
Wentao Gao,a* Mingchun Sun,a Yang Li,a Wei Li,a and Kimiaki Imafukub
aInstitute of Superfine Chemicals, Bohai University, Jinzhou 121000, China
bDepartment of Chemistry, Faculty of Science, Kumamoto University, Kurokami,
Kumamoto 8608555, Japan
*E-mail: isfc@bhu.edu.cn
Additional Supporting Information may be found in the online version of this article.
Received April 28, 2009
DOI 10.1002/jhet.243
Published online 10 November 2009 in Wiley InterScience (www.interscience.wiley.com).
The starting substrate 3-(3-(2-naphthyl)acryloyl)tropolone (1) was achieved by the aldol condensation
reaction of 3-acetyltropolone with 2-naphthaldehyde. Compound (1) reacted with bromine to give 7-
bromo-(2) and 5,7-dibromo-3-(3-(2-naphthyl)acryloyl)tropolone (3) according to the amount of the bro-
minated reagent. Iodination of 1 gave 7-iodo-3-(3-(2-naphthyl)acryloyl)tropolone (4). Azo-coupling
reactions of 1, 2, and 4 gave 5-arylazo-3-(3-(2-naphthyl)acryloyl) tropolones (5–8). Compounds 1–4
reacted with hydroxyamine to give 3-[2-(2-naphthyl)vinyl]-8H-cyclohepta[d]isoxazol-8-ones (9–12). The
reactions of 1–4 with phenylhydrazine and substituted phenylhydrazines gave 3-[2-(2-naphthyl)vinyl]-1-
phenylcyclohepta[c]pyrazol-8(1H)-ones (13–21).
J. Heterocyclic Chem., 46, 1302 (2009).
INTRODUCTION
pesticides [3], metals protease inhibition [4], and anti-
fungal plant genetic disease genes [5]. Therefore, natural
and synthetic tropolone derivatives have attracted con-
siderable interest to organic chemists. The synthesis of
substituted troponoids continues to be a considerable
synthetic challenge. We have reported the electrophilic
reactions of 3-acetyltropolone [6], 3-acetamidotropolone
Tropolone is an aromatic compound with a seven-
membered ring, a metabolite of Pseudomonas sp.; the
tropolone ring system represents the key structural ele-
ment in a wide range of natural products, many of
which are isolated from fungi [1] and higher plants [2].
Troponoids display various biological activities, such as
C
V
2009 HeteroCorporation

November 2009 Syntheses and Reactions of Halo- and Arylazo-Substituted 3-(3-(2-Naphthyl)acryloyl)-
tropolones: Formation of (Naphthalen-2-yl)vinyl)-Substituted Heterocycle-Fused Troponoid Compounds
1303
Scheme 1
Figure 1. The calculated electronegativity of compound 1.
[7], 3-cinnamoyltropolone [8], 3-isopropenyltropolone
[9], and 3-(2-quinolyl)tropolone [10], meanwhile various
fused-heterocyclic troponoids have been prepared. In
continuation of our interests in these compounds, we
report the synthesis of 3-(3-(2-naphthyl)acryloyl)tropo-
lone by the condensation of 3-acetyltropolone with
2-naphthaldehyde. 3-(3-(2-Naphthyl)acryloyl)tropolone
possesses similar structure to 3-cinnamonytropolone and
has three reactive parts for electrophilic reagents, two of
which are seven-membered tropolone ring and a naph-
thalene ring and the third is a propenyl part between the
two rings. Therefore, the reactions of 3-(3-(2-naphthyl)a-
cryloyl)tropolone with electrophilic reagents are also
expected to be interesting. On the other hand, the reac-
tions with nucleophilic reagents are also of interest for
participation of the tropolone ring, because chalcones
reacted with hydroxylamine [11–14] and hydrazine [15–
19] at the propenyl moiety to give diaryl-substituted iso-
xazolines and pyrazolines, respectively.
trum showed a proton singlet at 7.98 (s, 1H) assignable
to naphthalene H-1 and unresolved complex peaks at d
7.14–7.86 for the protons of the aromatic ring and the
exocyclic double bond. Moreover, the structure assigned
for this reaction product was fully supported by its mass
spectrum, which showed a molecular ion peak at 302
(Mþ).
By theoretical calculation, the 5- and 7-position of the
tropolone ring and the propenyl part have higher reac-
tive activities than the naphthalene ring for electrophilic
reagents, and their electronegativities are ꢁ0.150,
ꢁ0.204, and ꢁ0.219, respectively, as shown in Figure 1.
To verify the calculated results, compound 1 was
treated with some electrophilic reagents such as bro-
mine, iodine, and diazonium salts. Thus, compound 1
was first subjected to react with bromine. When 3-(3-(2-
naphthyl)acryloyl)tropolone (1) was reacted with bro-
mine in acetic acid in a mole ratio of 1:1 or 1:2, the
corresponding monosubstituted 7-bromo-3-(3-(2-naph-
thyl)acryloyl)tropolone (2) and disubstituted 5,7-
dibromo-3-(3-(2-naphthyl)acryloyl)tropolone (3) were
obtained in 67.7% and 73.2% yield, respectively
(Scheme 2).
This article deals with the preparation of 3-(3-(2-
naphthyl)acryloyl)tropolone as well as its electrophilic
substitution reactions with halo and diazonium salts and
the condensation reactions with hydroxylamine, phenyl-
hydrazine, and substituted phenylhydrazines.
The structure of 2 was determined by the elemental
analysis and spectral data. In the IR spectrum, an
absorption band for the hydroxyl group was at 3180
cmꢁ1, and the two typical carbonyl absorption bands
were observed at 1641 and 1601 cmꢁ1, respectively.
RESULTS AND DISCUSSION
1
The aldol condensation reactions of 3-acetyltropolone
with substituted benzaldehydes [20] and heterocyclic
aldehydes [21–23] have been reported. However, to our
knowledge, the research of 3-acetyltropolone with 2-
naphthaldehyde has never been performed, despite their
important potential biological activities. Thus, we tried
for the first time to study the preparation of 3-(3-(2-
naphthyl)acryloyl)tropolone (1) from 3-acetyltropolone
and 2-naphthaldehyde.
The H NMR spectrum showed a doublet at d 8.50 (d,
1H, J ¼ 8.5 Hz) assignable to tropolone H-4, a quartet
at 7.76 (q, 1H, J ¼ 10.0 Hz) attributable to tropolone
H-5, a doublet at 8.18 (d, 1H, J ¼ 10.0 Hz) for naphtha-
lene H-6, a doublet at 7.99 (d, 1H, J ¼ 6.3 Hz) for
naphthalene H-1, and a triplet at 7.16 (t, 1H, J ¼ 11.0
Hz) and a doublet at 7.26 (d, 1H, J ¼ 15.6 Hz) for the
proton of the carbon–carbon double bond, besides mul-
tiplet peaks at d 7.50–7.56 and 7.83–7.87 for the
Scheme 1 outlines the aldol condensation reaction of
3-acetyltropolone with 2-naphthaldehyde using aqueous
KOH (5%) as a catalyst and 50% methanol as solvent to
furnish 3-(3-(2-naphthyl)acryloyl)tropolone (1) in 85.3%
yield, mp 166–167ꢀC. Its structure was established from
the elemental analysis (C20H14O3) and spectral data.
In its IR spectrum, an absorption band for the
hydroxyl group was observed at 3190 cmꢁ1, and the
two typical carbonyl absorption bands were observed at
Scheme 2
1
1658 and 1613 cmꢁ1, respectively. The H NMR spec-
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W. Gao, M. Sun, Y. Li, W. Li, and K. Imafuku
Vol 46
Scheme 3
aromatic ring protons. It is worth mentioning that when
compound 1 was treated with three equivalents of bro-
mine, neither oxidative cyclization nor electrophilic
addition reaction on carbon–carbon double bond
occurred. Therefore, we concluded that the electrophilic
reactivity of the 5- and 7-position of the tropolone ring
were indeed higher than that of the naphthalene ring and
of the propenyl part. The reaction of 3-(3-(2-naphthyl)a-
cryloyl)tropolone (1) with excess iodine in the presence
of potassium carbonate afforded only the monosubsti-
tuted compound 7-iodo-3-(3-(2-naphthyl)acryloyl)tropo-
lone (6) in 51.9% yield. The reaction indicated that the
7-position of tropolone ring had the highest electrophilic
activity, which is in agreement with the theoretically
calculated results. In a similar method to compound 2,
the structures of 3 and 4 were also established from ele-
mental analysis and spectral data. In addition, although
the nitration of 3-acetyl, 3-acetamido, 3-cinnamoyl [6–
8], and 3-(2-quinolyl)tropolone [10] gave 5-nitro- and/or
5,7-dinitro-substituted products, when 3-(3-(2-naphthy-
l)acryloyl)tropolone (1) was treated with concentrated or
fuming nitric acid, any expected product was not
observed. The reaction may proceed with an unknown
mechanism that needs further investigation.
[6] and 3-cinnamoyltropolone [8] reacted with various
nucleophilic reagents bearing two reactive sides to give
a wide variety of heterocycle-fused troponoid com-
pounds [24].
The reactions of 3-(3-(2-naphthyl)acryloyl)tropolone
(1) with hydroxylamine in refluxing ethanol gave 3-[2-
(2-naphthyl)vinyl]-8H-cyclohepta[d]isoxazol-8-one (9)
in 47.7% yield. In the IR spectrum of 9, the disappear-
ance of characteristic hydroxyl and carbonyl absorption
for tropolone and the carbonyl group in the side chain
and the appearance of tropone carbonyl absorption at
1629 cmꢁ1 were clear evidence for the formation of a
new compound. Its 1H NMR spectrum showed the
absence of the hydroxy OH signal in addition to 7.12
(q, 1H, J ¼ 8.5 Hz), 7.23 (d, 1H, J ¼ 16.0 Hz) for car-
bon–carbon double bond protons, 7.29 (d, 1H, J ¼ 12.6
Hz) for tropolone H-7, 7.44 (dd, 1H, J ¼ 4.0, 8.2 Hz)
for tropolone H-5, 7.77 (q, 1H, J ¼ 16.5 Hz) for tropo-
lone H-6, 7.98 (s, 1H) for naphthalene H-1, 8.21 (d, 1H,
J ¼ 4.5 Hz) for tropolone H-4, besides an unresolved
complex peaks in the aromatic region at d 7.51–7.54
and 7.85–7.90. The mass spectrum exhibited a molecu-
lar ion 299 (Mþ), which matched the expected molecu-
lar weight for the corresponding compound 9. The ele-
mental analysis further supported the assigned structure.
The vital characteristic structure of compound 9 could
be authenticated by a simple method: when the com-
pound was developed on thin layer chromatography
(TLC) (silica gel: GF254, developing agent: ethyl ace-
tate), there was only one main spot with no tailing, as
well as giving a negative coloring test with iron (b)
chloride in ethanol solution. In a similar way, the reac-
tions of compounds 2, 3, and 4 with hydroxylamine also
afforded the corresponding 5-substituted or 5,7-substi-
tuted 3-[2-(2-naphthyl)vinyl]-8H-cyclohepta[d]isoxazol-
8-ones (10–12), and their structures were determined on
the basis of a negative coloring test with iron (III) chlo-
ride and the elemental analysis as well as on spectral
data (Scheme 4).
The azo-coupling reaction of tropolone took place
exclusively at the 5-position to give crystalline dyes.
The reactions of 3-(3-(2-naphthyl)acryloyl)tropolone (1)
with diazonium salts gave 5-arylazo-substituted 3-(3-(2-
naphthyl)acryloyl)tropolones (5 and 6) in 47.8% and
76.2% yield, respectively. The compounds (2) and (4)
were also reacted with p-toluidine diazonium salt to
afford 7-bromo-3-(3-(2-naphthyl)acryloyl)-5-(p-tolyldia-
zenyl)tropolone (7) and 7-iodo-3-(3-(2-naphthyl)acry-
loyl)-5-(p-tolyldiazenyl)tropolone (8) in 28.5% and
20.9% yield, respectively. These structures were con-
firmed from the elemental analysis and spectral data
(see Experimental section). For example, in the IR spec-
trum of compound 5, an absorption band for the
hydroxyl group was at 3185 cmꢁ1, for the tropolone car-
bonyl group was at 1648 cmꢁ1, and for the propenyl
1
carbonyl group was at 1608 cmꢁ1. Its H NMR spec-
trum showed peaks at d 8.53 (d, 1H, J ¼ 2.1 Hz) for
tropolone H-4, at 8.31 (q, 1H, J ¼ 2.2 Hz) for tropolone
H-6, at 7.99 (s, 1H) for naphthalene H-1, at 7.74 (dd,
1H, J ¼ 16.0, 2.2 Hz) for tropolone H-7, and an unre-
solved complex peaks at d 7.73–7.93 and 7.34–7.59 for
the protons of the aromatic ring and carbon–carbon dou-
ble bond (Scheme 3).
As attacking site of nucleophilic reagents, chalcones
have an enone moiety that connects two benzene rings.
Thus, it has been reported that the chalcones reacted
with hydroxylamine [11–14] and hydrazine [15–19] to
afford diphenyl-substituted isoxazolines and pyrazolines,
respectively. On the other hand, we found that 3-acetyl
When a solution of 3-(3-(2-naphthyl)acryloyl)tropo-
lone (1) and phenylhydrazine in ethanol was refluxed
for 18 h, the 3-[2-(2-naphthyl)vinyl]-1-phenylcyclohep-
ta[c]pyrazol-8(1H)-one (13) was isolated in 19.3% yield.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009 Syntheses and Reactions of Halo- and Arylazo-Substituted 3-(3-(2-Naphthyl)acryloyl)-
tropolones: Formation of (Naphthalen-2-yl)vinyl)-Substituted Heterocycle-Fused Troponoid Compounds
1305
Scheme 4
naphthyl)acryloyl)tropolone (1) as yellow crystals, yield
85.3%; mp 166–167ꢀC; IR (KBr): 3190 (OH), 1658 (C¼¼O),
1613 (C¼¼O) cmꢁ1
;
1H NMR (CDCl3): d 7.14–7.86 (m, 12H,
Ar-H and HC¼¼CH), 7.98 (s, 1H, 2-NaphthH-1); ms: m/z 303
(Mþ1)þ. Anal. Calcd. for C20H14O3: C, 79.46; H, 4.67. Found:
C, 79.30; H, 4.52.
7-Bromo-3-(3-(2-naphthyl)acryloyl)tropolone (2). To
a
stirred solution of 3-(3-(2-naphthyl) acryloyl)tropolone (0.302
g, 1 mmol) and sodium acetate (0.125 g) in acetic acid (50
mL), a solution of bromine (0.160 g, 1 mmol) in acetic acid (2
mL) was added dropwise at room temperature. After the reac-
tion was completed, water (100 mL) was added. The precipi-
tate was collected and recrystallized from ethyl acetate to give
7-bromo-3-(3-(2-naphthyl)acryloyl)tropolone as yellow crys-
tals, yield 70.6%; mp 182–184ꢀC; IR (KBr): 3180 (OH), 1641
Its structure was confirmed from the elemental analysis
(C26H18N2O) and spectral data. The IR spectrum
showed the absorption for tropone carbonyl group at
1
1630 cmꢁ1. Its H NMR spectrum showed the absence
1
(C¼¼O), 1601 (C¼¼O) cmꢁ1; H NMR (CDCl3): d 7.16 (t, 1H,
of the hydroxy OH signal, and all the protons were
observed at d 6.86 (q, 1H, J ¼ 8.4 Hz) for tropolone
H-5, 7.94 (s, 1H) for naphthalene H-1, 6.99 (d, 1H, J ¼
12.5 Hz) for one proton of carbon–carbon double bond,
7.25–7.30 (m, 1H) for tropolone H-7, 7.44–7.52 (m,
8H), 7.77–7.87 (m, 6H) for the aromatic region and the
other protons of carbon–carbon double bond. The
compound (1) reacted with 4-nitro, 4-bromo, 4-chloro,
4-methoxy, and 3-chlorophenylhydrazines to give 3-(2-
(2-naphthyl)vinyl)-1-(4-nitrophenyl)cyclohepta[c]pyra-
zol-8 (1H)-one (14), 1-(4-bromophenyl)-3-(2-(2-naph-
thyl)vinyl)cyclohepta[c]pyrazol-8(1H)-one (15), 1-(4-
chlorophenyl)-3-(2-(2-naphthyl)vinyl)cyclohepta[c]pyra-
zol-8(1H) -one (16), 1-(4-methoxyphenyl)-3-(2-(2-naph-
thyl)vinyl)cyclohepta[c]pyrazol-8(1H)-one (17), and 1-
(3-chlorophenyl)-3-(2-(2-naphthyl)vinyl)cyclohepta[c]-
pyrazol-8(1H) -one (18) in 57.6%, 53.8%, 43.3%,
26.2%, and 41.2% yield, respectively. The electro-
philic substitution products (2–4) reacted with phenyl-
hydrazine and also gave the corresponding 1,8-dihy-
drocycloheptapyrazol-8-one derivatives (19–21). In
conclusion, this investigation has demonstrated the
synthesis of naphthalene-substituted tropolones and
troponoids compounds (Scheme 5).
AC¼¼CH, J ¼ 11.0 Hz), 7.26 (d, 1H, CH¼¼CA, J ¼ 15.6 Hz),
7.50–7.56 (m, 2H, Ar-H), 7.76 (q, 1H, tropolone H-5, J ¼
10.0 Hz), 7.83–7.87 (m, 4H, Ar-H), 7.99 (d, 1H, 2-NaphthH-1,
J ¼ 6.3 Hz), 8.18 (d, 1H, tropolone H-6, J ¼ 10.0 Hz), 8.50
(d, 1H, tropolone H-4, J ¼ 8.5 Hz); ms: m/z 381 (Mþ1)þ.
Anal. Calcd. for C20H13BrO3: C, 63.01; H, 3.44. Found: C,
62.97; H, 3.20.
5,7-Dibromo-3-(3-(2-naphthyl)acryloyl)tropolone (3). To a
stirred solution of sodium acetate and 3-(3-(2-naphthyl)acry-
loyl)tropolone (0.302 g,1 mmol) in acetic acid, a solution of
bromine (0.320 g, 2 mmol) in acetic acid (2 mL) was added
dropwise at room temperature. After completion, the mixture
was poured into water (150 mL), and then the precipitate was
collected and recrystallized from ethyl acetate to give 5,7-
dibromo-3-(3-(2-naphthyl)acryloyl)tropolone as yellowish blue
powder, yield 72.3%; mp 212–213ꢀC; IR (KBr): 3185 (OH),
1647 (C¼¼O), 1592 (C¼¼O) cmꢁ1
;
1H NMR (CDCl3): d 7.25
(d, 1H, AC¼¼CH, J ¼ 15.9 Hz), 7.50–7.56 (m, 2H, Ar-H),
7.71 (q, 1H, AC¼¼CH, J ¼ 1.6 Hz), 7.83–7.87 (m, 4H, Ar-H),
7.78 (d, 1H, tropolone H-6, J ¼ 15.9 Hz), 7.99 (s, 1H, 2-
NaphthH-1), 8.50 (d, 1H, tropolone H-4, J ¼ 2.0 Hz); ms: m/z
461 (Mþ1)þ. Anal. Calcd. for C20H12Br2O3: C, 52.21; H,
2.63. Found: C, 52.01; H, 2.45.
7-Iodo-3-(3-(2-naphthyl)acryloyl)tropolone
(4). To
a
stirred mixture of 3-(3-(2-naphthyl)acryloyl)tropolone (0.302
g,1 mmol) and potassium carbonate (0.305 g) in water (0.85
mL), a solution of iodine (0.325 g) and potassium iodide
(0.325 g) in water (1.85 mL) was added in an ice water bath.
After being stirred for 11.5 h, excess iodine was reduced with
EXPERIMENTAL
The melting points were determined by using WRS-1B
1
melting points apparatus. H NMR was measured with a Var-
Scheme 5
ian Inova 500 NMR spectrometer at 500 MHz or a Varian
Inova 400 NMR spectrometer at 400 MHz. The reported
chemical shifts were against TMS. Mass spectra were deter-
mined using a MSD VL ESII spectrometer. Elemental analysis
was performed using an Elementar Vario EL-III element
analyzer.
3-(3-(2-Naphthyl)acryloyl)tropolone (1). To a stirred solu-
tion of 3-acetyltropolone and 2-naphthaldehyde in 50% metha-
nol, a solution of 5% KOH aqueous was added dropwise at
room temperature. Having monitored by TLC, and after the
reaction was completed, the mixture was acidified with 6M hy-
drochloric acid to precipitate yellow crystals. The crystals
were collected and recrystallized from ethanol to give 3-(3-(2-
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W. Gao, M. Sun, Y. Li, W. Li, and K. Imafuku
Vol 46
sodium hydrogen sulfite. The mixture was acidified with 6M
hydrochloric acid (80 mL) to precipitate pale greenish crystals.
The crystals were collected and recrystallized from ethyl ace-
tate to give 7-iodo-3-(3-(2-naphthyl)acryloyl)tropolone as pale
greenish crystals, yield 52.0%; mp 197–198ꢀC; IR (KBr):
ethanol (5 mL) was refluxed for 12 h. The precipitate was
collected and recrystallized from acetic acid to give 3-[2-(2-
naphthyl)vinyl]-8H-cyclohepta[d]isoxazol-8-one as pale brown
powder, yield 47.7%; mp 252–253ꢀC; IR (KBr): 1629 (C¼¼O),
1573 (C¼¼N) cmꢁ1
;
1H NMR (CDCl3): d 7.12 (q, 1H,
3179 (OH), 1670 (C¼¼O), 1585 (C¼¼O) cmꢁ1
;
1H NMR
CH¼¼CA, J ¼ 8.5 Hz), 7.23 (d, 1H, AC¼¼CH, J ¼ 16.0 Hz),
7.51–7.54 (m, 2H, Ar-H), 7.29 (d, 1H, tropolone H-7, J ¼
12.6 Hz), 7.44 (dd, 1H, tropolone H-5, J ¼ 4.0, 8.2 Hz), 7.77
(q, 1H, tropolone H-6, J ¼ 16.5 Hz), 7.85–7.90 (m, 4H, Ar-
H), 7.98 (s, 1H, 2-NaphthH-1), 8.21 (d, 1H, tropolone H-4, J
(CDCl3): d 6.78 (t, 1H, CH¼¼CA, J ¼ 10.25 Hz), 7.29 (d, 1H,
AC¼¼CH, J ¼ 15.9 Hz), 7.49–7.54 (m, 2H, Ar-H), 7.82–7.86
(m, 4H, Ar-H), 7.57 (dd, 1H, tropolone H-5, J ¼ 7.5, 4.0 Hz),
7.75 (d, 1H, tropolone H-6, J ¼ 10.2 Hz), 7.98 (s, 1H,
2-NaphthH-1), 8.49 (d, 1H, J ¼ 10.0 Hz, tropolone H-4); ms:
m/z 429 (Mþ1)þ. Anal. Calcd. for C20H13IO3: C, 56.10; H,
3.06. Found: C, 56.14; H, 2.85.
¼
4.5 Hz); ms: m/z 300 (Mþ1)þ. Anal. Calcd. for
C20H13NO2: C, 80.25; H, 4.38; N, 4.68. Found: C, 80.17; H,
4.01; N, 4.82.
3-(3-(2-Naphthyl)acryloyl)-5-(phenyldiazenyl)tropolone (5). To
an ice-cooled stirred solution of compound 1 (0.302 g, 1
mmol) in pyridine (4 mL), arenediazonium chloride solution (2
mmol, 2 mL), prepared from aniline or p-toluidine, was added
dropwise. After additional stirring for 2–3 h, the precipitate was
collected and recrystallized from benzene or ethyl acetate to
give product (5) as pale yellow crystals, yield 47.8%; mp 190–
7-Bromo-3-[2-(2-naphthyl)vinyl]-8H-cyclohepta[d]isoxazol-8-
one (10). A solution of 7-bromo-3-(3-(2-naphthyl)acryloyl)tro-
polone (0.100 g) and hydroxylamine hydrochloride (0.036 g)
in ethanol (5 mL) was refluxed for 20 h. The precipitate was
collected and recrystallized from acetic acid to give 7-bromo-
3-[2-(2-naphthyl)vinyl]-8H-cyclohepta[d]isoxazol-8-one
as
golden powder, yield 41.4%; mp 243–244ꢀC; IR (KBr): 1670
191ꢀC; IR (KBr): 3185 (OH), 1648 (C¼¼O), 1608 (C¼¼O) cmꢁ1
;
;
(C¼¼O), 1549 (C¼¼N) cmꢁ1 1H NMR (CDCl3): d 7.30–7.79
1H NMR (CDCl3): d 7.34–7.59 (m, 6H, Ar-H and CH¼¼CH),
7.74 (dd, 1H, tropolone H-7, J ¼ 16.0, 2.2 Hz), 7.73–7.93 (m,
7H, Ar-H), 7.99 (s, 1H, 2-NaphthH-1), 8.31 (q, 1H, tropolone
H-6, J ¼ 2.2 Hz), 8.53 (d, 1H, tropolone H-4, J ¼ 2.1 Hz); ms:
m/z 407 (Mþ1)þ. Anal. Calcd. for C26H18N2O3: C, 76.83; H,
4.46; N, 6.89. Found: C, 76.79; H, 4.29; N, 6.87.
(m, 8H, Ar-H and CH¼¼CH), 7.53 (q, 1H, tropolone H-5, J ¼
3.2 Hz), 7.88 (d, 1H, tropolone H-6, J ¼ 6.8 Hz), 7.94 (s, 1H,
2-NaphthH-1), 8.41(d, 1H, tropolone H-4, J ¼ 10.0 Hz); ms:
m/z 378 (Mþ1)þ. Anal. Calcd. for C20H12BrNO2: C, 63.51; H,
3.20; N, 3.70. Found: C, 63.33; H, 3.50; N, 3.59.
5,7-Dibromo-3-[2-(2-naphthyl)vinyl]-8H-cyclohepta[d]isoxa-
zol-8-one (11). A solution of 5,7-dibromo-3-(3-(2-naphthyl)a-
cryloyl)tropolone (0.100 g) and hydroxylamine hydrochloride
(0.030 g) in ethanol (5 mL) was refluxed for 28 h. The precipi-
tate was collected and recrystallized from ethyl acetate to give
5,7-dibromo-3-[2-(2-naphthyl)vinyl]-8H-cyclohepta[d]isoxazol-
8-one as brown crystals, yield 60.7%; mp 196–197ꢀC; IR
3-(3-(2-Naphthyl)acryloyl)-5-(p-tolyldiazenyl)tropolone
(6). The same experimental method as compound (5) was fol-
lowed. This compound was obtained as deep red powder, yield
76.2%; mp 173–174ꢀC; IR (KBr): 3203 (OH), 1673 (C¼¼O),
1610 (C¼¼O) cmꢁ1
;
1H NMR (CDCl3): d 2.44 (s, 3H, CH3),
7.30–7.58 (m, 6H, Ar-H and CH¼¼CH), 7.73 (q, 1H, tropolone
H-7, J ¼ 1.5 Hz), 7.82–7.86 (m, 6H, Ar-H), 7.99 (s, 1H, 2-
NaphthH-1), 8.28 (q, 1H, tropolone H-6, J ¼ 2.1 Hz), 8.50 (d,
1H, tropolone H-4, J ¼ 2.0 Hz); ms: m/z 421 (Mþ1)þ. Anal.
Calcd. for C27H20N2O3: C, 77.13; H, 4.79; N, 6.66. Found: C,
77.11; H, 4.58; N, 6.53.
1
(KBr): 1679 (C¼¼O), 1560 (C¼¼N) cmꢁ1; H NMR (CDCl3): d
7.89–7.24 (m, 8H, Ar-H and CH¼¼CH), 7.78 (d, 1H, tropolone
H-6, J ¼ 12.7 Hz), 7.99 (s, 1H, 2-NaphthH-1), 8.51 (d, 1H,
tropolone H-4, J ¼ 1.5 Hz); ms: m/z 458 (Mþ1)þ. Anal.
Calcd. for C20H11Br2NO2: C, 52.55; H, 2.43; N, 3.06. Found:
C, 52.41; H, 3.39; N, 3.18.
7-Bromo-3-(3-(2-naphthyl)acryloyl)-5-(p-tolyldiazenyl)tro-
polone (7). The same experimental method as compound (5)
was followed. The compound was obtained as orange crystals,
yield 38.5%; mp > 290ꢀC; IR (KBr): 3210 (OH), 1673
7-Iodo-3-[2-(2-naphthyl)vinyl]-8H-cyclohepta[d]isoxazol-8-one
(12). A solution of 7-iodo-3-(3-(2-naphthyl)acryloyl)tropolone
(0.100 g) and hydroxylamine hydrochloride (0.032 g) in ethanol
(5 mL) was refluxed for 24 h. The precipitate was collected and
recrystallized from tetrahydrofuran to give 7-iodo-3-[2-(2-naph-
thyl)vinyl]-8H-cyclohepta[d]isoxazol-8-one as pale brown pow-
der, yield 41.0%; mp 275ꢀC decomposition; IR (KBr): 1692
1
(C¼¼O), 1608 (C¼¼O) cmꢁ1; H NMR (CDCl3): d 2.45 (s, 3H,
ACH3), 7.31–7.80 (m, 6H, Ar-H and CH¼¼CH), 7.84–7.87 (m,
6H, Ar-H), 8.00 (s, 1H, 2-NaphthH-1), 8.38 (d, 1H, tropolone
H-6, J ¼ 2.0 Hz), 9.02 (d, 1H, tropolone H-4, J ¼ 1.6 Hz);
ms: m/z 499 (Mþ1)þ. Anal. Calcd. for C27H19BrN2O3: C,
64.94; H, 3.84; N, 5.61. Found: C, 64.89; H, 3.50; N, 5.65.
7-Iodo-3-(3-(2-naphthyl)acryloyl)-5-(p-tolyldiazenyl)tropo-
lone (8). The same experimental method of compound (7) was
followed. This compound was obtained as deep red crystals,
yield 20.9%; mp > 290ꢀC; IR (KBr): 3304 (OH), 1682
(C¼¼O), 1617 (C¼¼O) cmꢁ1; d 2.45 (s, 3H, ACH3), 7.30–7.55
(m, 3H, Ar-H and CH¼¼CA), 7.75–7.87 (m, 9H, Ar-H and
AC¼¼CH), 8.00 (s, 1H, 2-NaphthH-1), 8.36 (d, 1H, tropolone
H-6, J ¼ 2.0 Hz), 9.26 (d, 1H, tropolone H-4, J ¼ 1.6 Hz);
ms: m/z 547 (Mþ1)þ. Anal. Calcd. for C27H19IN2O3: C,
59.35; H, 3.51; N, 5.13. Found: C, 59.38; H, 3.1 6; N, 5.10.
(C¼¼O), 1602 (C¼¼N) cmꢁ1
;
1H NMR (CDCl3): d 6.81–7.24
(m, 2H, CH¼¼CH), 7.85–7.90 (m, 6H, Ar-H), 7.53 (q, 1H, trop-
olone H-5, J ¼ 3.6 Hz), 7.78 (d, 1H, tropolone H-6, J ¼ 8.4
Hz), 7.99 (s, 1H, 2-NaphthH-1), 8.76 (d, 1H, tropolone H-4, J
¼ 9.2 Hz); ms: m/z 426 (Mþ1)þ. Anal. Calcd. for C20H12INO2:
C, 56.49; H, 2.84; N, 3.29. Found: C, 56.42; H, 2.61; N, 3.34.
Synthesis of 2-vinyl naphthalene heterocycle-fused tropo-
noid compounds (13–18). A mixture of 3-(3-(2-naphthyl)acry-
loyl)tropolone (0.151 g, 0.5 mmol) and substituted phenylhy-
drazines (1 mmol) in ethanol (10 mL) was refluxed for 18–28
h. The precipitates were collected and recrystallized to give
the products.
3-[2-(2-Naphthyl)vinyl]-8H-cyclohepta[d]isoxazol-8-one (9). A
solution of 3-(3-(2-naphthyl)acryloyl)tropolone (0.151 g, 0.5
mmol) and hydroxylamine hydrochloride (0.071 g, 1 mmol) in
3-[2-(2-Naphthyl)vinyl]-1-phenylcyclohepta[c]pyrazol-8(1H)-one
(13). This compound was obtained as golden needles, yield
19.3%; mp 193–194ꢀC; IR (KBr): 1630 (C¼¼O), 1600 (C¼¼N)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009 Syntheses and Reactions of Halo- and Arylazo-Substituted 3-(3-(2-Naphthyl)acryloyl)-
tropolones: Formation of (Naphthalen-2-yl)vinyl)-Substituted Heterocycle-Fused Troponoid Compounds
1307
cmꢁ1
;
1H NMR (CDCl3): d 6.86 (q, 1H, tropolone H-5, J ¼
7.47–7.52 (m, 6H, Ar-H and CH¼¼CH), 7.81–7.90 (m, 7H, Ar-
8.4 Hz), 6.99 (d, 1H, CH¼¼CA, J ¼ 12.5 Hz), 7.25–7.30 (m,
1H, tropolone H-7), 7.44–7.52 (m, 8H, Ar-H and CH¼¼CA),
7.77–7.87 (m, 6H, Ar-H), 7.94 (s, 1H, 2-NaphthH-1); ms: m/z
375 (Mþ1)þ. Anal. Calcd. for C26H18N2O: C, 83.40; H, 4.85;
N, 7.48. Found: C, 83.17; H, 5.30; N, 7.45.
H), 7.94 (s, 1H, 2-NaphthH-1), 8.28 (d, 1H, tropolone H-6, J
¼ 6.8 Hz), 8.51 (d, 1H, tropolone H-4, J ¼ 8.0 Hz); ms: m/z
453 (Mþ1)þ. Anal. Calcd. for C26H17BrN2O: C, 68.89; H,
3.78; N, 6.18. Found: C, 68.70; H, 3.47; N, 6.07.
5,7-Dibromo-3-[2-(2-naphthyl)vinyl]-1-phenylcyclohepta[c]-
pyrazol-8(1H)-one (20). A mixture of 5,7-dibromo-3-(3-(2-
naphthyl)acryloyl)tropolone (0.100 g) and phenylhydrazine
hydrochloride (0.048 g) in absolute ethanol (5 mL) was
refluxed for 22 h. The precipitate was collected and recrystal-
lized from ethyl acetate to give 5,7-dibromo-3-[2-(2-naphthyl)-
vinyl]-1-phenylcyclohepta[c] pyrazol-8(1H)-one as orange
crystals, yield 35.0%; mp > 290ꢀC; IR (KBr): 1656 (C¼¼O),
3-(2-(2-Naphthyl)vinyl)-1-(4-nitrophenyl)cyclohepta[c]pyra-
zol-8(1H)-one (14). This compound was obtained as brown
powder, yield 57.6%; mp 280ꢀC decomposition; IR (KBr):
1630 (C¼¼O), 1604 (C¼¼N) cmꢁ1; H NMR (CDCl3): d 6.95–
1
7.10 (m, 2H, Ar-H and CH¼¼CA), 7.43–7.51 (m, 4H, Ar-H
and AC¼¼CH), 7.66 (d, 2H, Ar-H, J ¼ 9.2 Hz), 7.80–7.89 (m,
6H, Ar-H), 7.96 (s, 1H, 2-NaphthH-1), 8.37 (d, 2H, Ar-H, J ¼
9.2 Hz); ms: m/z 420 (Mþ1)þ. Anal. Calcd. for C26H17N3O3:
C, 74.45; H, 4.09; N, 10.02. Found: C, 74.51; H, 4.38; N,
9.99.
1591 (C¼¼N) cmꢁ1
;
1H NMR (CDCl3): d 7.26–7.53 (m, 5H,
Ar-H and CH¼¼CH), 7.80–7.87 (m, 8H, Ar-H), 7.95 (s, 1H, 2-
NaphthH-1), 8.16 (d, 1H, tropolone H-6, J ¼ 1.6 Hz), 8.52 (d,
1H, tropolone H-4, J ¼ 1.6 Hz); ms: m/z 533 (Mþ1)þ. Anal.
Calcd. for C26H16Br2N2O: C, 58.67; H, 3.03; N, 5.26. Found:
C, 58.63; H, 3.29; N, 5.33.
1-(4-Bromophenyl)-3-(2-(2-naphthyl)vinyl)cyclohepta[c]-
pyrazol-8(1H)-one (15). This compound was obtained as yel-
low crystals, yield 53.8%; mp 284–285ꢀC; IR (KBr): 1625
(C¼¼O), 1576 (C¼¼N) cmꢁ1; H NMR (CDCl3): d 6.91 (t, 1H,
1
7-Iodo-3-[2-(2-naphthyl)vinyl]-1-phenylcyclohepta[c]pyrazol-
8(1H)-one (21). A mixture of 7-iodo-3-(3-(2-naphthyl)acry-
loyl)tropolone (0.100 g) and phenylhydrazine hydrochloride
(0.051 g) in absolute ethanol (5 mL) was refluxed for 47 h.
The precipitate was collected and recrystallized from ethyl ac-
etate to give 7-iodo-3-[2-(2-naphthyl)vinyl]-1-phenylcyclohep-
ta[c]pyrazol-8(1H)-one as yellowish blue powder, yield 24.0%;
tropolone H-5, J ¼ 5.6 Hz), 7.01 (d, 1H, CH¼¼CA, J ¼ 8.0
Hz), 7.26–7.64 (m, 8H, Ar-H and CH¼¼CA), 7.77–7.86 (m,
6H, Ar-H), 7.95 (s, 1H, 2-NaphthH-1); ms: m/z 453 (Mþ1)þ.
Anal. Calcd. for C26H17BrN2O: C, 68.89; H, 3.78; N, 6.18.
Found: C, 68.80; H, 3.87; N, 6.07.
1-(4-Chlorophenyl)-3-(2-(2-naphthyl)vinyl)cyclohepta[c]-
pyrazol-8(1H)-one (16). This compound was obtained as pale
yellow crystals, yield 26.2%; mp 212–213ꢀC; IR (KBr): 1652
mp >290ꢀC; IR (KBr): 1635 (C¼¼O), 1581 (C¼¼N) cmꢁ1
;
1H
NMR (CDCl3): d 6.60 (t, 1H, tropolone-5, J ¼ 10.0 Hz),
7.41–7.43 (m, 2H, CH¼¼CH), 7.43–7.52 (m, 5H, Ar-H), 7.79–
7.88 (m, 6H, Ar-H), 7.87 (d, 1H, tropolone H-6, J ¼ 2.4 Hz),
7.94 (s, 1H, 2-NaphthH-1), 8.63 (d, 1H, tropolone-4, J ¼ 9.6
Hz); ms: m/z 501 (Mþ1)þ. Anal. Calcd. for C26H17IN2O: C,
62.41; H, 3.42; N, 5.60. Found: C, 62.32; H, 3.64; N, 5.71.
(C¼¼O), 1590 (C¼¼N) cmꢁ1
;
1H NMR (CDCl3): d 6.90–7.02
(m, 2H, Ar-H and AC¼¼CH), 7.27 (d, 1H, tropolone H-7, J ¼
11.2 Hz), 7.39–7.50 (m, 7H, Ar-H and CH¼¼CA), 7.77–7.88
(m, 6H, Ar-H), 7.94 (s, 1H, 2-NaphthH-1); ms: m/z 409
(Mþ1)þ. Anal. Calcd. for C26H17ClN2O: C, 76.37; H, 4.19; N,
6.85. Found: C, 76.30; H, 3.95; N, 6.80.
1-(4-Methoxyphenyl)-3-(2-(2-naphthyl)vinyl)cyclohepta[c]-
pyrazol-8(1H)-one (17). This compound was obtained as
golden powder, yield 43.3%; mp 277–278ꢀC; IR (KBr): 1660
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(KBr): 1639 (C¼¼O), 1574 (C¼¼N) cmꢁ1; H NMR (CDCl3): d
6.91 (q, 1H, tropolone H-5, J ¼ 10.0 Hz), 7.02 (d, 1H,
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet