Reaction of acridine with pyrazolone derivatives

Article abstract of DOI:10.1002/jhet.5570420533

A mixture of acridine and a pyrazolone derivative was reacted in the solid state (without solvent). It is proposed that the enol tautomer (the C4-position) of the pyrazolone derivative attacks the C9-position of acridine through a nucleophilic reaction resulting in products where the C4-position of pyrazolone is connected to the C9-position of acridine. When the reaction of 3-methyl-1-phenyl-5-pyrazolone and acridine was earned out at low temperature (25°-50°), the reaction product was obtained even when the majority of the reaction mixture had not melted. The same reaction was also carried out in the presence of an ultrasonic wave at same temperature (25°-50°) and the reaction product was obtained in high yield. Under ultrasonic conditions, the reaction mixture was not melted. However, the interface between 3-methyl-1-phenyl-5-pyrazolone and acridine gradually changed from white to black. In this reaction, the dihydroacridine dimer is not obtained.

Full text of DOI:10.1002/jhet.5570420533

Jul-Aug 2005
963
Reaction of Acridine with Pyrazolone Derivatives
Yoshimi Ishihara*, Takeyuki Ito, Hiroshi Saito, Jiro Takano
Department of Chemistry, School of Science, Tokai University,
1117 Kitakaname, Hiratsuka-shi, Kanagawa, Japan, 259-1292
Received October 5, 2004
A mixture of acridine and a pyrazolone derivative was reacted in the solid state (without solvent). It is pro-
posed that the enol tautomer (the C4-position) of the pyrazolone derivative attacks the C9-position of acri-
dine through a nucleophilic reaction resulting in products where the C4-position of pyrazolone is connected
to the C9-position of acridine. When the reaction of 3-methyl-1-phenyl-5-pyrazolone and acridine was car-
ried out at low temperature (25°-50°), the reaction product was obtained even when the majority of the reac-
tion mixture had not melted. The same reaction was also carried out in the presence of an ultrasonic wave at
same temperature (25°-50°) and the reaction product was obtained in high yield. Under ultrasonic condi-
tions, the reaction mixture was not melted. However, the interface between 3-methyl-1-phenyl-5-pyrazolone
and acridine gradually changed from white to black. In this reaction, the dihydroacridine dimer is not
obtained.
J. Heterocyclic Chem., 42, 963 (2005).
Introduction.
methyl-5-pyrazolone, 3-methyl-1-p-tolyl-5-pyrazolone,
1,3-dimethyl-5-pyrazolone and 2,3-dimethyl-1-phenyl-5-
pyrazolone. The reaction mechanism is also discussed.
Acheson et al. and Hamana et al. studied the reactions of
pyridine and quinoline N-oxide compounds with nucle-
ophilic reagents in solution [1-7]. Also mixtures of acri-
dine and various vinyl ethers in methanol under reflux
conditions have been shown to produce dihydroacridinyl
derivatives [8].
Results and Discussion.
Solid State Reaction of Acridine with Pyrazolone
Derivatives.
Reaction of acridine with different pyrazolone deriva-
tives at different temperatures is shown in Table 1 for a
molar ratio of acridine:pyrazolone derivative of 1:2. The
pyrazolone derivatives used were 3-methyl-1-phenyl-5-
pyrazolone, 3-methyl-5-pyrazolone, 1-(4'-nitrophenyl)-3-
methyl-5-pyrazolone, 3-methyl-1-p-tolyl-5-pyrazolone,
1,3-dimethyl-5-pyrazolone and 2,3-dimethyl-1-phenyl-5-
pyrazolone. The resulting products were thus, 4-(9-
acridinyl)-3-methyl-1-phenyl-5-pyrazol-5-ol 1 (black-pur-
ple needles), 4-(9-acridinyl)-3-methyl-5-pyrazol-5-ol 2
(yellow needles), 4-(9-acridinyil)-1-(4'-nitrophenyl)-3-
methyl-5-pyrazol-5-ol 3 (brown needles), 4-(9-acridinyl)-
3-methyl-1-p-tolyl-5-pyrazol-5-ol 4 (black-violet needles),
4-(9-acridinyl)-1,3-dimethyl-5-pyrazol-5-ol 5 (red-brown
needles) and 4-(9-acridinyl)-2,3-dimethyl-1-phenyl-5-
pyrazol-5-ol 6 (orange-yellow needles), respectively. The
reaction conditions and yields of the reaction products are
shown in Table 1 and Scheme 1.
It seems that the normal pyrazolone derivatives react by
nucleophilic attack to the C9-position of acridine, suggest-
ing that the pyrazolone ring takes the resonance structure
of the enol form. All of these reactions of acridine and
pyrazolone derivatives were considered to occur via the
enol form of pyrazolone where the C4-position of pyra-
zolone attacks the C9-position of acridine, except for 2,3-
dimethyl-1-phenyl-5-pyrazolone. Because 2,3-dimethyl-
1-phenyl-5-pyrazolone has groups substituted at the 1-,
2-and 3-positions, the pyrazolone ring cannot adopt the
enol form and thus the product must occur via the keto
form. All products obtained from these reactions are C9
We previously reported that the reaction of acridine with
nucleophilic reagents without solvent produced condensa-
tion products [9,10]. For instance, acridine derivatives
have been formed in high yields using mixture of acri-
dinium chloride and aniline heated at 110 °C and from
mixtures of acridine and methylindole derivatives heated
at 160 °C. Pyrrole, pyrrole derivatives and imidazole
derivatives have been used as nucleophilic reagents in the
non-solvent reactions with acridine as well [11,12].
Furthermore, acridine and phenol or resorcinol were
reacted at 210° without solvent [13], and finally an
equimolar mixture of acridine and sodium amide was
heated at 130 °C without solvent to successfully produce
acridine derivatives [14].
Pyrrole is well known to be able to discharge a proton to
become an anion. In the reaction, the proton migrates to
the nitrogen atom of acridine to generate the N-protonated.
In the N-protonated form, the C9-position of acridine is
susceptible to nucleophilic substition [9,10].
In this study, we try to use the pyrazolone as the nucle-
ophile in a non-solvent reaction with acridine. The car-
bonyl group at the C5-position of pyrazolone increases the
electron density at the C4-position of pyrazole, which
allows for nucleophilic substitution at the C9-position of
acridine in manner similar to that of pyrole. It is possible
that pyrazolone reacts at low temperature in the solid state.
This study reports on the reaction of π-deficient pyra-
zolone derivatives with acridine at low temperature with-
out solvent. We examined 3-methyl-1-phenyl-5-pyra-
zolone, 3-methyl-5-pyrazolone, 1-(4'-nitrophenyl)-3-

964
Y. Ishihara, T. Ito, H. Saito, J. Takano
Vol. 42
Table 1
In particular, 3-methyl-1-phenyl-5-pyrazolone and 3-
methyl-1-p-tolyl-5-pyrazolone reacted at lower tempera-
tures (50°) even when it was observed that most of the raw
material was not melted. Furthermore, the reaction
occurred at room temperature for 3-methyl-1-phenyl-5-
pyrazolone providing the product in high yield. Figure 1
(1) shows a photograph of the complete mixture of acri-
dine and 3-methyl-1phenyl-5-pyrazolone before heating at
50°. Figure 1 (2) shows a color change of the mixture of
acridine and 3-methyl-1phenyl-5-pyrazolone after heating
at 50° for 5 hours. The color of the mixture changed from
white to dark-gray. Figure 2 (1) shows a photograph of the
interface of 3-methyl-1-phenyl-5-pyrazolone and acridine
layers before heating at 50°. Figure 2 (2) shows the color
change of the interface between the 3-methyl-1-phenyl-5-
pyrazolone and acridine layers after heating at 50° for 5
hours. The color of the interface changed from white to
black, suggesting that a reaction was occurring in the solid
state.
Reaction Products of Acridine with Pyrazolone Derivatives
Pyrazolons
Products Reaction conditions Yield (%)
Temp.(°) Time (hr)
3-methyl-1-phenyl-5-pyrazolone
1
Room Temp.
30
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
26.6
32.6
33.7
35.5
41.9
52.9
0
70.9
90.9
0
75.5
92.8
19.5
53.5
41.2
0
67.5
82.1
0
40
50
100
150
50
100
150
50
100
50
50
100
150
50
100
150
50
3-methyl- 5-pyrazolone
2
3
4
5
6
1-(4'-nitorophenyl)-3-methyl
-5-pyrazolone
3-methyl-1-p-tolyl-5-pyrazolone
1,3-dimethyl- 5-pyrazolone
2,3-Dimethyl-1-phenyl-5-pyrazolone is known to be
acidic. In face, 2,3-dimethyl-1-phenyl-5-pyrazolone can
even give up a proton in the keto form. As a result, a pyra-
zolone ring of 2,3-dimethyl-1-phenyl-5-pyrazolone takes
an enamine structure under this reaction condition, and it is
thought that an anion is generated at the C4-position of
pyrazolone ring. Therefore, it was supposed that the reac-
2,3-dimethyl-1-phenyl-5-pyrazolone
100
150
0
35.0
substituted acridines. The yields of products varied for
different structures of pyrazolone derivatives.

Jul-Aug 2005
Reaction of Acridine with Pyrazolone Derivatives
965
in a sealed glass reaction tube (inside diameter, 15 mm)
under nitrogen gas. The reaction tube was then immersed
in an ultrasonic bath, and subjected to ultrasonic wave for
5 hours at either room temperature (25°) or at 50°. The
pyrazolone derivatives were the same as those used in the
previous reaction. Only the substrates 3-methyl-1-phenyl-
5-pyrazolone and 3-methyl-1-p-tolyl-5-pyrazolone suc-
cessfully reacted to give the acridine derivatives 1 and 4,
respectively. The yields of 1 and 4 are increased through
ultrasonication for 5 hours at room temperature (25°) and
50° as shown in Table 2. The yield of the product 1 was
48.5% at room temperature (25°), and 59.6% at 50°. The
yield of 4 was 14.6% at 50°.
(1)
(2)
Fig.1 Change in state of mixture of acridine and 3-methyl-1phenyl-5-
pyrazolone: (1) initially; (2) after heating for 5hr at 50 .
o
Effect of Recrystallization Solvents on the Reaction
Product of Acridine with 3-Methyl-1-phenyl-5-pyra-
zolone.
After the mixture of acridine and 3-methyl-1-phenyl-5-
pyrazolone was heated at 50° for 5 hours, the product was
dissolved in methanol, acetone, benzene, chloroform,
DMSO and THF, and then allowed to cool for recrystal-
lization purposes. After each solvent was removed, the
residual substance was taken up into diethylether, and was
recrystallized again in the same solvent as before. Black-
purple needle of product 1 were only obtained from recrys-
tallization in methanol or chloroform. The yield of 1 from
recrystallization in methanol was 35.5% (see Table 1), but
in chloroform was only 17.3%. It is thought that product 1
deteriorated in the chloroform.
(1)
(2)
Fig.2 Change in state of two-layer of acridine and 3-methyl-1phenyl-5-
pyrazolone: (Upper part: 3-methyl-1-phenyl-5-pyrazolone, Lower part:
acridine.) (1) initially; (2) after heating for 5hr at 50 .
o
Table 2
Yields of Products from Reaction of Acridine with Pyrazolone
Derivatives after Ultrasonic Wave. Reaction Products are
4-(9-acridinyl)-3-methyl-1-phenyl-5-pyrazol-5-ol 1 and
4-(9-acridinyl)-3-methyl-1-p-tolyl-5-pyrazol-5-ol 4.
Solvent Reaction of Acridine with 3-Methyl-1-phenyl-5-
pyrazolone.
Products
Reaction conditions
Temp.(°) Time (hr)
Yield (%)
To investigate the solvent reaction, acridine and 3-
methyl-1-phenyl-5-pyrazolone were dissolved in several
solvents. In a series of reactions, a mixture of acridine
(0.125 g, 0.70 mmol) and 3-methyl-1-phenyl-5-pyrazolone
(0.244 g, 1.40 mmol) were completely dissolved in 50 ml
of solvent, and were reacted at room temperature (25°) for
5 hours. The solvents used were methanol, acetone, ben-
zene, chloroform, DMSO and THF. After the reaction, the
solvent was removed and the residual substance was taken
up into diethylether. The material was then recrystallized
in the same solvent as used in the reaction. Of the solvents
tested, only methanol produced the black-purple needles of
product 1 in 18.4% yield. For the reactions carried in other
solvents, 1 was not obtained. Notably, the yield of 1 for
the synthesis in methanol was less than for the non-solvent
reaction (see Table 1).
1
4
Room Temp
5
5
5
5
48.5
59.6
0
50
Room Temp
50
14.6
tion product was the keto-formed acridinium derivative in
a low yield (Yield of 35%).
In this reaction system, it was found that the dihy-
droacridinyl derivatives were not produced. It is thought
that most of the dihydroacridinyl derivatives were not able
to form the reaction intermediate. Therefore, acridine does
not draw hydrogen from pyrazolone derivatives, and acri-
dine reacted with pyrazolone derivatives directly. It is sup-
posed that C9-acridine substitution bodies are reaction
products when obtained it.
Conclusion.
Supersonic Reaction of Acridine with Pyrazolone
Derivatives.
Acridine and pyrazolone derivatives were investigated
in the solid-state reaction, in the supersonic reaction, and
in various solvents. As a result of the investigations, it was
shown that the reaction occurs successfully in the solid
A mixture including acridine (2.80 mmol) and the
respective pyrazolone derivative (5.60 mmol) was placed

966
Y. Ishihara, T. Ito, H. Saito, J. Takano
Vol. 42
starting materials. Steam distillation of the methanol fraction
removed the methanol and the resulting residue was washed with
methanol to yield the acridine derivative, 4-(9-acridinyl)-3-
methyl-5-pyrazol-5-ol 2, mp 301-302° as yellow needles; ir
(potassium bromide): 3460(ν O-H), 1590, 1500, 1420, 1315(ν N-
state. Furthermore, it appears that the reaction of acridine
and 3-methyl-1-phenyl-5-pyrazolone is a very specific
reaction involving the enol form of 3-methyl-1-phenyl-5-
pyrazolone. Reaction product was provided in high yield.
-1
1
H), 760(δ C-H) cm ; ms: EI (m/Z) 275; H nmr (deuteri-
omethanol CD OD): δ 1.97 (s, 3H), 7.58, 7.63 (tt, 3H, J=4.58 Hz,
J=4.54 Hz), 7.87 (q, 2Η, J=4.94 Hz), 7.96 (d, 1Η, J=5.04 Hz),
8.02 (quintet, 3Η, J=4.15 Hz).
EXPERIMENTAL PROCEDURES.
Measurements.
3
Anal. Calcd. For C
H ON : C, 74.17; H, 4.76; N, 15.26.
17 13 3
Melting points were determined on a Yamato melting point
apparatus model MP-21 and were not corrected. The ir spectra
Found: C, 75.55; H, 4.76; N, 14.45.
4-(9-Acridinyl)-1-(4'-nitrophenyl)-3-methyl-5-pyrazol-5-ol (3).
1
were taken on a Shimadzu FT-IR 4200 spectrophotometer. H
13
nmr and C nmr spectra were measured with a Bruker FT-NMR
A mixture of acridine (0.501 g, 2.80 mmol) and 1-(4'-nitro-
phenyl)-3-methyl-5-pyrazolone (1.226 g, 5.60 mmol) was placed
in a sealed glass reaction tube (inside diameter, 15 mm) under
nitrogen gas. After the reaction tube was heated for 5 hours at
50° or 100° or 150°, the resulting product was dissolved in
methanol. Then the reaction mixture was washed with
diethylether to remove unreacted starting materials. Steam distil-
lation of the methanol fraction removed the methanol and the
resulting residue was washed with methanol to yield the acridine
derivative, 4-(9-acridinyl)-1-(4'-nitrophenyl)-3-methyl-5-pyra-
zol-5-ol 3, mp 301-302° as brown needles; ir (potassium bro-
mide): 3300(ν O-H), 1600, 1580(ν N-H), 1510, 1420(ν N-O),
AVANC-E500 spectrometer. The EI mass spectra were taken on
a Shimadzu GC-MS-QP1000EX or Shimadzu GC-MS-QP5050A
spectrometers. The elemental analyses were measured by
YANOCO CHN CODER NT-5.
Solid State Reaction of Acridine with Pyrazolone Derivatives.
Reaction of acridine with different pyrazolone derivatives at
different temperatures is shown in Table 1 for a molar ratio of
acridine:pyrazolone derivative of 1:2. The used pyrazolone
derivatives were 3-methyl-1-phenyl-5-pyrazolone, 3-methyl-5-
pyrazolone, 1-(4'-nitrophenyl)-3-methyl-5-pyrazolone, 3-methyl-
1-p-tolyl-5-pyrazolone, 1,3-dimethyl-5-pyrazolone and 2,3-
dimethyl-1-phenyl-5-pyrazolone. The resulting products were
thus, 4-(9-acridinyl)-3-methyl-1-phenyl-5-pyrazol-5-ol 1, 4-(9-
acridinyl)-3-methyl-5-pyrazol-5-ol 2, 4-(9-acridinyl)-1-(4'-nitro-
phenyl)-3-methyl-5-pyrazol-5-ol 3, 4-(9-acridinyl)-3-methyl-1-
p-tolyl-5-pyrazol-5-ol 4, 4-(9-acridinyl)-1,3-dimethyl-5-pyrazol-
5-ol 5 and 4-(9-acridinyl)-2,3-dimethyl-1-phenyl-5-pyrazol-5-ol
6, respectively.
−1
1
820(δ C-H)
; ms: EI (m/Z) 396; H nmr (deuteriomethanol
CD OD): δ 1.99 (d, 3H, J=4.95 Hz), 6.61 (d, 2H, J=5.49 Hz),
3
7.64 (t, 2H, J=2.58 Hz), 7.98 (t, 2H, J=2.75 Hz), 8.15 (d, 2H,
J=5.22 Hz), 8.34 (d, 2H, J=6.19 Hz).
Anal. Calcd. For C
H O N : C, 68.69; H, 4.07; N, 14.13.
23 16 3 4
Found: C, 68.02; H, 4.04; N, 15.08.
4-(9-Acridinyl)-3-methyl-1-p-tolyl-5-pyrazol-5-ol (4).
A mixture of acridine (0.501 g, 2.80 mmol) and 3-methyl-1-p-
tolyl-5-pyrazolone (1.054 g, 5.60 mmol) was placed in a sealed
glass reaction tube (inside diameter, 15 mm) under nitrogen gas.
After the reaction tube was heated for 5 hours at 50° or 100° or
150°, the resulting product was dissolved in methanol. Then the
reaction mixture was washed with diethylether to remove unre-
acted starting materials. Steam distillation of the methanol frac-
tion removed the methanol and the resulting residue was washed
with methanol to yield the acridine derivative, 4-(9-acridinyl)-3-
methyl-1-p-tolyl-5-pyrazol-5-ol 4, mp 268-269° as black violet
needles; ir (potassium bromide): 3450(ν O-H), 2910, 2850(ν C-
4-(9-Acridinyl)-3-methyl-1-phenyl-5-pyrazol-5-ol (1).
A mixture of acridine (0.501 g, 2.80 mmol) and 3-methyl-1-
phenyl 5-pyrazolone (0.974 g, 5.60 mmol) was placed in a sealed
glass reaction tube (inside diameter, 15 mm) under nitrogen gas.
After the reaction tube was heated for 5 hours at 50° or 100° or
150°, the resulting product was dissolved in methanol. Then the
reaction mixture was washed with diethylether to remove unre-
acted starting materials. Steam distillation of the methanol frac-
tion removed the methanol and the resulting residue was washed
with methanol to yield the acridine derivative, 4-(9-acridinyl)-3-
methyl-1-phenyl-5-pyrazol-5-ol 1, mp 267-268° as black purple
needles; ir (potassium bromide): 3450(ν O-H), 1580, 1510, 1450,
-1
H), 1600, 1550, 1510(ν N-H), 1300, 820, 720(δ C-H) cm ; ms:
1
EI (m/Z) 365; H nmr (deuteriomethanol CD OD): δ 2.02 (s,
3
-1
1
1350(ν N-H), 770, 695(δ C-H) cm ; ms: EI (m/Z) 285; H nmr
3H), 2.41 (s, 3H), 7.65 (t, 2H, J=4.98 Hz), 7.71 (d, 2H, J=5.01
Hz), 7.94 (t, 2H, J=4.58 Hz), 8.178(t, 4H, J=6.23 Hz).
(deuteriomethanol CD OD): δ 2.02 (s, 3H), 7.32 (t, 1H, J=4.44
3
Hz), 7.87 (q, 2Η, J=4.94 Hz), 7.51 (t, 2H, J=4.77 Hz), 7.65 (t, 2H,
J=4.75 Hz), 7.87 (d, 2H, J=4.79 Hz), 7.87 (d, 2H, J=4.79 Hz),
8.19 (t, 4H, J=4.61 Hz).
Anal. Calcd. For C
Found: C, 78.16; H, 5.39; N, 11.31.
H ON : C, 78.88; H, 5.24; N, 11.50.
24 19 3
4-(9-Acridinyl)-1,3-dimethyl-5-pyrazol-5-ol (5).
Anal. Calcd. For C
H ON : C, 78.61; H, 4.88; N, 11.96.
23 17 3
A mixture of acridine (0.501 g, 2.80 mmol) and 1,3-methyl-5-
pyrazolone (0.627 g, 5.60 mmol) was placed in a sealed glass
reaction tube (inside diameter, 15 mm) under nitrogen gas. After
the reaction tube was heated for 5 hours at 50° or 100° or 150°,
the resulting product was dissolved in methanol. Then the reac-
tion mixture was washed with diethylether to remove unreacted
starting materials. Steam distillation of the methanol fraction
removed the methanol and the resulting residue was washed with
methanol to yield the acridine derivative, 4-(9-acridinyl)- 1,3-
Found: C, 78.94; H, 4.93; N, 12.05.
4-(9-Acridinyl)-3-methyl-5-pyrazol-5-ol (2).
A mixture of acridine (0.501 g, 2.80 mmol) and 3-methyl-5-
pyrazolone (0.549 g, 5.60 mmol) was placed in a sealed glass
reaction tube (inside diameter, 15 mm) under nitrogen gas. After
the reaction tube was heated for 5 hours at 50° or 100° or 150°,
the resulting product was dissolved in methanol. Then the reac-
tion mixture was washed with diethylether to remove unreacted

Jul-Aug 2005
Reaction of Acridine with Pyrazolone Derivatives
967
methyl-5-pyrazol-5-ol 5, mp 300-302° as red brown needles; ir
(potassium bromide): 3450(ν O-H), 2910(ν C-H), 1620, 1560,
1480(ν N-H), 760(δ C-H) cm ; ms: EI (m/Z) 289; H nmr (deu-
solved in methanol, acetone, benzene, chloroform, DMSO or
THF. And these solvent were used in a recrystallization process.
After each solvent was removed, the residual substance was taken
up into diethylether. Again, the product was recrystallized in the
same solvent as before. Black-purple needles of 1 (mp 267-268°)
were obtained from recrystallization in methanol or chloroform.
The recrystallization yield of 1 from methanol was 35.5%, but the
yield of the product 1 from chloroform was only 17.3%.
-1
1
teriomethanol CD OD): δ 1.94 (s, 3H), 3.67 (s, 3H), 7.60 (t, 2H,
3
J=4.59 Hz), 7.89 (t, 2H, J=4.61 Hz), 8.00 (d, 2H, J=5.1Hz), 8.19
(d, 2H, J=5.25Hz).
Anal. Calcd. For C
H ON : C, 74.72; H, 5.23; N, 14.52.
18 15 3
Found: C, 74.93; H, 5.32; N, 14.52.
4-(9-Acridinyl)-2,3-dimethyl-1-phenyl-5-pyrazol-5-ol (6).
Solvent Reaction of Acridine with 3-Methyl-1-phenyl-5-pyra-
zolone.
A mixture of acridine (0.501 g, 2.80 mmol) and 2,3-methyl-1-
phenyl-5-pyrazolone (1.054 g, 5.60 mmol) was placed in a sealed
glass reaction tube (inside diameter, 15 mm) under nitrogen gas.
After the reaction tube was heated for 5 hours at 50° or 100° or
150°, the resulting product was dissolved in methanol. Then the
reaction mixture was washed with diethylether to remove raw
materials of non-reaction. Steam distillation of the methanol frac-
tion removed the methanol and the resulting residue was washed
with methanol to yield the acridine derivative, 4-(9-acridinyl)-
2,3-methyl-1-phenyl-5-pyrazol-5-ol 6, mp 238-239° as orange
yellow needles; ir (potassium bromide): 1660(ν C-O), 1580,
A mixture of acridine (0.125 g, 0.70 mmol) and 3-methyl-1-
phenyl-5-pyrazolone (0.244 g, 1.40 mmol) was completely dis-
solved in 50 ml of solvent, and was reacted at room temperature
(25°) for 5 hours. The solvents used were methanol, acetone,
benzene, chloroform, DMSO and THF. After the reaction, sol-
vent was removed and the residual substance was taken up into
diethylether. The product material was then recrystallized in the
same solvent as used in the reaction. In the case of methanol,
black-purple needle of product 1 (mp 267-268°) were obtained at
18.4%. For the reactions in other solvents, 1 was not obtained.
-1
1
1500, 1440(ν N-H), 740(δ C-H) cm ; ms: EI (m/Z) 365; H nmr
(deuteriomethanol CD OD): δ 2.02 (s, 3H), 3.34 (s, 3H), 7.36 (t,
1H, J=7.43 Hz), 7.55 (quintet, 6H, J=7.58 Hz), 7.77 (t, 2H,
J=7.65 Hz), 7.99 (t, 2H, J=8.85 Hz), 8.28 (t, 2H, J=8.7 Hz).
3
REFERENCES AND NOTES
[1] R. M. Acheson, L. E. Orgel, The Chemistry of
Heterocyclic Compounds Acridines, Interscience Publishers, Inc.,
New York (1956).
Anal. Calcd. For C
H ON : C, 78.86; H, 5.24; N, 11.50.
24 19 3
Found: C, 78.86; H, 5.07; N, 11.43.
[2] M. Hamana and M. Yamazaki, Chem. Pharm. Bull., 11,
415 (1963).
[3] M. Hamana and H. Noda, Chem. Pharm. Bull., 13, 912
(1965).
[4] M. Hamana and H. Noda, Chem. Pharm. Bull., 15, 1380
(1967).
[5] M. Hamana and H. Noda, Chem. Pharm. Bull., 18, 26
(1970).
Supersonic Reaction of Acridine with Pyrazolone Derivatives.
A mixture including acridine (2.80 mmol) and the respective
pyrazolone derivative (5.60 mmol) was placed in a sealed glass
reaction tube (inside diameter, 15 mm) under nitrogen gas. The
reaction tube was then immersed in an ultrasonic bath, and sub-
jected to ultrasonic wave for 5 hours at either room temperature
(25°) or at 50°.
The pyrazolone derivatives were the same as those used in the
previous reaction. The Pyrazolone derivatives were 3-methyl-1-
phenyl-5-pyrazolone, 3-methyl-5-pyrazolone, 1-(4'-nitrophenyl)-
3-methyl-5-pyrazolone, 3-methyl-1-p-tolyl-5-pyrazolone, 1,3-
dimethyl-5-pyrazolone and 2,3-dimethyl-1-phenyl-5-pyrazolone.
The crude product for these samples was dissolved in
methanol and washed with diethylether to unreacted starting
materials. Steam distillation of the methanol fraction removed
the methanol and the resulting residue was washed with methanol
to give the acridine derivatives 1 and 4. The yield of the product
1 was 48.5% at room temperature (25°), and 59.6% at 50°. The
yield of 4 was 14.6% at 50°.
[6] M. Hamana and H. Noda, J. Pharmaceutical Society of
Japan, 89, 641 (1969).
[7] M. Hamana and O. Hoshino, J. Pharmaceutical Society of
Japan, 84, 35 (1964).
[8] R. Takano, Y. Ishihara, T. Kitahara and J. Takano, J.
Heterocyclic Chem., 33, 1403 (1996).
[9] J. Takano, T. Kitahara and K. Shirai, J. Chemical Society of
Japan, 400 (1983).
[10] T. Kitahara, J. Takano and K. Shirai, J. Chemical Society of
Japan, 122 (1987).
[11] J. Takano, T. Kitahara and K. Shirai, J. Chemical Society of
Japan, 519 (1984).
[12] Y. Ishihara, T. Kitahara and J. Takano, Pro. School Sci.
Tokai Univ., XXXII, 105 (1997).
[13] J. Takano, T. Kitahara and K. Shirai, Pro. School Sci. Tokai
Univ., XIX, 91 (1984).
Effect of Recrystallizaion Solvent on the Reaction Product of
Acridine with 3-Methyl-1-phenyl-5-pyrazolone.
After the reaction mixture of acridine and 3-methyl-1-phenyl-5-
pyrazolone was heated at 50° for 5 hours, the product was dis-
[14] T. Kitahara, Y. Ishihara and J. Takano, J. Chemical Society
of Japan, 876 (1997).