Synthesis of some pyrido-imidazophenazine derivatives

Article abstract of DOI:10.1080/10426500701415980

2,3-Diaminophenazine (1) was prepared1, 2, 3. Attempts were made to review the chemistry of phenazine8, biology of phenazine derivatives and also a review on fused phenazine derivatives; for studying their pharmacological15 and photoconductive properties17.

Full text of DOI:10.1080/10426500701415980

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Phosphorus, Sulfur, and Silicon
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Synthesis of Some Pyrido-
Imidazophenazine Derivatives
A. A. El Bahnasawy a & M. F. El Ahwany a
a Faculty of Science, Chemistry Department, Zagazig
University, Egypt
Published online: 15 Jun 2007.
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Pyrido-Imidazophenazine Derivatives, Phosphorus, Sulfur, and Silicon and the Related
Elements, 182:8, 1937-1944
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Phosphorus, Sulfur, and Silicon, 182:1937–1944, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701415980
Synthesis of Some Pyrido-Imidazophenazine Derivatives
A. A. El Bahnasawy
M. F. El Ahwany
Faculty of Science, Chemistry Department, Zagazig University, Egypt
2,3-Diaminophenazine (1) was prepared1−3. Attempts were made to review the
chemistry of phenazine4−8, biology of phenazine derivatives and also a review on
fused phenazine derivatives; for studying their pharmacological9−15 and photocon-
ductive properties16,17
.
Keywords Antitumor; condensation; diketone; phenazine; photo conductivity
CONCLUSION
Potential building blocks in our program are 2,3-diaminophenazine and
2-(cyanomethyl)-imidazo[4,5-b]phenazine (2). we prepared a number of
pyrido-imidazophenazine derivatives in order to elucidate further the
effect of nitrogen atom ring substituents on the relative biological18−20
and photo conductive properties.
RESULTS AND DISCUSSION
The structure of 2,3-diaminophenazine (1) was confirmed through com-
1
parison of its physical data with reported data.1−3 The H-NMR spec-
trum of (1) in DMSO4-d6 exhibited signals at δ 6.26 (s, 4H, 2NH2) which
disappear by deuteration with D2O, 6.92 (s, 2H, Harm.), 7.53 (m, 2H,
Harom.) and 7.88 (m, 2H, Harom.).
The condensation reaction of (1) with ethylcyanoacetate in n-butanol
under reflux condition, compound (2) was obtained in high yield. The
chemical structure of compound (2) was confirmed by elemental anal-
ysis and spectral data. The IR spectrum showed absorption bands at
3465 cm−1 broad due to NH group, 3120 cm−1 due to carbonyl hydro-
gen aromatic bond, 2920 cm−1due to carbon aliphatic, 1623 cm−1 due to
carbon nitrogen double and 1610–1480 cm−1 due to (C N) conjugated.
Address correspondence to A. A. El Bahnasawy, Faculty of Science, Chemistry De-
partment, Zagazig University, Egypt. E-mail: aelbahnasawy@gmail.com
1937

1938
A. A. El Bahnasawy and M. F. El Ahwany
TABLE I Analytical Data of the Prepared Compounds
Analysis
Calculated/Found
Comp.
no.
m.p.
◦C
Yield/solvent
of cryst.
Molecular formula
(mol. Wi.)
C
H
N
1
172
185
78
Acetic acid
67
C12H10N4
(210.16)
C15H9N5
(259.27)
68.58
68.82
69.48
69.71
74.28
74.13
73.05
73.24
70.14
70.32
68.05
68.24
71.36
71.52
74.60
74.46
75.61
75.79
65.25
65.08
74.41
74.62
4.81
4.74
3.50
3.62
4.05
4.13
4.01
4.16
3.41
3.28
4.23
4.15
4.12
4.31
3.65
3.81
3.81
3.76
3.95
3.87
3.38
3.44
26.66
26.72
27.01
26.76
21.66
21.72
22.94
22.78
21.53
21.65
17.64
17.82
15.61
15.46
21.75
21.69
20.58
20.72
21.14
21.33
18.08
17.87
2
Bu.
63
DMF
71
DMF
59
3
234
C20H13N5
(323.35)
C26H17N7
(427.47)
C19H11N5O
(325.33)
4
278
5a
6a
6b
7
256
EtOH
67
DMF
73
Acetic acid
81
DMF/H2O
73
Bu.
64
EtOH
74
DMF/H2O
269
C
27H20N6O3
(476.49)
>300
280
C32H22N6O3
(538.56)
C24H14N6
(386.41)
8
>300
249
C30H18N7
(476.51)
C18H13N5O2
(331.33)
C24H13N5O
(387.39)
9
10
>300
It was of interest to study the condensation reactions of (2) with
the appropriate 1,3-diketones and their hydrazonyl derivatives (namely
acetyl acetone, ethoxycarbonyl ketones and/or their hydrazonyl deriva-
tives in acetic acid/acetic anhydride under reflux condition to af-
ford the corresponding pyrido[1,6-a]imidazo[4,5-b]phenazine deriva-
tives (3), (4), (5a,b) and/or (6a,b) respectively.
Chemical and spectroscopic evidences for the synthesized compounds
are presented (c.f. Tables I and II).
For example compound (6a) was established on the basis of its ele-
mental analysis and spectral data. Thus, the IR spectrum of (6a) showed
absorption band at 3470 cm−1 broad due to free (OH) group, 1910 cm−1
due to N N , 1760 cm−1 due to carbonyl ester group, 1623 cm−1 due
to carbon nitrogen double bond and 1158, 1193due to (C O C) group.
1
The H-NMR spectrum of (6a) in DMSO-d6 exhibited bands at 1.3
(t, 3H, CH3), 2.6 (s, 3H, CH3), 4.1–4.2 (m, 2H, O-CH2CH3), 7.2 (br., 1H,
OH), 7.4 (m, 5H, Harom.), 7.9 (m, 2H, Harom.) and 9.1 (s, 2H, Harom.).

Synthesis of Some Pyrido-Imidazophenazine Derivatives
1939
TABLE II Spectral Data for Selected Compounds
Comp. no.
IR (νmax/cm−1
)
1H-NMR (δ/ppm)
1
3400–3320 (NH2), 3098 C
H
6.26 (s, 4H, 2NH2), disappear by
(arom.), 1610–1480 (C C)
conj., 162 (C N)
deuteration with D2O, 6.92 (s, 2H,
Hrom.), 7.53 (m, 2H, arom.) and 7.88
(m, 2H, arom.)
2
4
3465 (NH) cyclic, 3120 (C H)
arom., 2920 ( CH) aliph.,
1610–1480 (C N) conj.,
1623 (C N)
4.6 (s, 2H, CH2-), 7.9 (m, 2H, arom.),
8.42 (m, 2H, arom.), 9.1 (s, 2H, arom.)
and 12.9 (br.(s), 1H, NH).
3120 (CH) arom., 2930 (CH)
aliph., 2210 (C≡N), 1890
2.6 (s, 6H, 2CH3), 7.4 (m, 5H, arom.),
7.86 (m, 2H, arom.); 8.38 (m, 2H,
arom.) and 9.12 (s, 2H, arom.)
(N
N ), 1624 (C N),
1616–1510 (C C) conj.
3480 (OH), 2220 (C≡N), 1620
(C N)
5b
6a
6.9 (s, 1H, arom.), 7.2 (br., 1H, OH); 7.4
(m, 5H, arom.); 7.8 (m, 2H, arom.); 8.3
(m, 2H, arom.) and 9.08 (s, 2H, arom.)
1.3 (t, 3H, CH3), 4.1–4.2 (m, 2H,
o-CH2CH3); 2.6 (s, 3H, CH3); 7.2 (br.,
1H, OH); 7.4 (m, 5H, arom.); 7.9 (m,
2H, arom.); 8.4 (m, 2H, arom.) and 9.1
(s, 2H, arom.)
3470 (OH), 1910 (N
N ),
1760 (C O) ester, 1623
(C N), 1158, 1193
(C
O C)
7
8
3300–3180 (NH2), 3100 (CH)
arom., 2210 (C≡N), 1620
(C N)
6.3 (s, 2H, NH2); 7.2 (s, 1H arom.); 7.4
(m, 5H, arom.); 7.84 (m, 2H, arom.),
8.37 (m, 2H, arom), 9.12 (s, 2H, arom.)
6.3 (s, 2H, NH2), 7.3 (m, 10H, arom.),
7.87 (m, 2H, arom.); 8.43 (m, 2H,
arom.) and 9.12 (s, 2H, arom.)
3390–3280 (NH2), 3098 (CH)
arom., 2210 (C≡N), 1910
(N
N ), 1624 (C N),
1610–1485 (C C) conj.
3100 (CH) arom., 2910 (CH)
aliph., 2210 (C≡N), 1760
(C O) ester, 1624 (C N),
9
1.4 (t, 3H, CH3); 4.2–4.3 (m, 2H,
OCH2CH3); 4.7 (s, 2H, CH2CN), 7.83
(m, 2H, arom.), 8.39 (m, 2H, arom.)
and 9.08 (s, 2H, arom.)
1160, 1195 (C
O C)
10
3098 (CH) arom., 2220 (C≡N),
3.6 (s, 2H, CH2); 7.4 (m, 5H, arom.); 7.84
(m, 2H, arom.); 8.41 (m, 2H, arom.);
and 9.12 (s, 2H, arom.)
1720 (C O), 1623 (C N)
Reaction of compound (2) with cyanoacetophenone, hydrazonyl-
acetophenone and/or ethyl chloroformate in acetic acid/acetic anhydride
under reflux condition give the corresponding pyrido[1,6-a]imidazo[4,5-
b]phenazine derivatives (7), (8) and/or (9) respectively.
Condensation reactions of (2) with different ketones such as acetone
and/or acetophenone in ethanol/piperidine under reflux condition, yield
the corresponding pyridoimidazophenazine derivatives (5a), and/or (10)
respectively. Finally compounds (3) and/or (7) can be coupled with dia-
zonium salts such as phenyldiazonium chloride in ethanol/sod. acetate
to afford the corresponding compounds (4) and/or (8) respectively.

1940
A. A. El Bahnasawy and M. F. El Ahwany
Compound (7) was established on the basis of its elemental analysis
and spectral data. Thus, the IR spectrum of (7) showed absorption bands
at 3300–3180 cm−1 due to (NH2), 3100 cm−1 due to carbon hydrogen
aromatic bond, 2210 cm−1 due to cyano group and 1820 cm−1 due to
carbon nitrogen double bond.
Also compound (10), was established on the basis of its elemen-
1
tal analysis and spectral data. Thus the H-NMR spectrum of (10) in
DMSO-d6 exhibited bands at 3.6 (s, 2H, CH2), 7.4 (m, 5H, Harom.), 7.84
(m, 2H, Harom.), 8.41 (m, 2H, Harom.) and 9.12 (s, 2H, Harom.).
EXPERIMENTAL
Melting points uncorrected determined on a Gallen Kamp melting point
apparatus. I.R. spectra were recorded in KBr using a Shimadu spectra
1
200–91506 spectrophotometer. H NMR in DMSO as a solvent on a
varian 90MHz using TMS as the internal reference. Elemental analyses
were carried out in the Microanalytical unit, Cairo University, Giza,
Egypt.
1) Preparation of 2,3-Diaminophenazine (1)
Finally powdered o-phenylenediamine (54.0 g, 0.5 mol) was dissolved
in conc. hydrochloric acid (83.3 ml) and distilled water (2.5 L).A filtered
solution of ferric chloride (400 g) in (750 ml) water was added slowly
and the mixture was stirred mechanically.
After standing overnight at room temperature the red-brown
coloured crystalline product was filtered off, washed with cold dilute
0.3N hydrochloric acid until free from ferric ions, then dissolved in hot
water (2.5 L), 2,3-diaminophenazine was precipitated by the addition
of a concentrated solution of potassium hydroxide. The product was
filtered off, washed with water and dried at 100–110◦C. The strongly
alkaline filterate was heated and acidified (pH 4.5) with glacial acetic
acid. After cooling, 2-amino-3-hydroxyphenazine was collected, washed
with water and dried at 100–110◦C. The crude products used without
further purification.
2) Reaction of Compound (1) with Ethyl Cyanoacetate
A mixture of 2,3-diaminophenazine (1) (0.21 g, 1.0 mmol) and ethyl-
cyanoacetate (0.11 g, 1.0 mmol) in n-butanol (30ml) was heated

Synthesis of Some Pyrido-Imidazophenazine Derivatives
1941
under reflux for 8hours. After cooling the formed precipitate was
filtered off, dried and recrystallized from the proper solvent to obtain
2-(cyanomethyl)-imidazo[4,5-b]phenazine (2).
3) Reaction of Compound (2) with Different 1,3-Diketones and
Their Hydrazonyl Derivatives
A mixture of compound (2) (0.26 g, 1.0 mmol) and different 1,3-diketones
and their hydrazonyl derivatives (namely, acetyl acetone, ethoxycar-
bonyl ketones and/or their hydrazonyl derivatives (1.0 mmol) in 20 ml)
acetic acid and (5 ml) acetic anhydride was refluxed for 3–5hours. The
product obtained was filtered off and recrystallized from a suitable
solvent to give the corresponding pyrido[1,6-a]imidazo[4,5-b]phenazine
derivatives (3), (5a,b), (4) and/or (6a,b) respectively.
4) Reaction of Compound (2) with Different Nitriles and/or
Ethyl Chloroformate
A mixture of compound (2) (0.26g, 1.0mmol) and different nitriles and/or
ethyl chloroformate (namely, cyanoacetophenone, hydrazonylcyano-
acetophenone and/or ethyl chloroformate (1.0 mmol) in acetic acid
(30 ml) and (5 ml) acetic anhydride was refluxed for 4 hours. The
product obtained was filtered off and recrystallized from a suitable sol-
vent to afford the corresponding pyrido[1,6-a]imidazo[4,5-b]phenazine
derivatives (7), (8) and/or N-substituted-2-(cyanomethyl)imidzo[4,5-
b]phenazine derivative (9).
5) Reaction of N-Substtuted-2-(cyanomethyl)imidazo[4,5-b]
phenazine (9) with Different Ketones
A mixture of compound (9) (0.33g, 1.0mmol) and different ketones such
as acetone and/or acetophenone (1.0 mmol) in ethanol (20 ml) contain-
ing piperidine (0.5 ml). The reflux mixture was refluxed for 3hours.
Product was collected by filtration, crystallized from the proper sol-
vent to obtain the corresponding pyrido[1,6-a]imidazo[4,5-b]phenazine
derivatives (5a) and /or (10) respectively.
6) Coupling Reactions with Diazonium Salts
To a solution of compound (3) and/or (7) (1.0 mmol) in ethanol
(20 ml), sodium acetate (0.25 g, 3.0 mmol) followed by diazonium
salts as phenyl diazonium chloride was added over a (30) minutes

1942
A. A. El Bahnasawy and M. F. El Ahwany
CHART 1
period while stirring for an hour. The reaction mixture was left over
night in a refrigerator at 4◦C. The solid product was filtered off and
recrystallized from the proper solvent to afford the correspond-
ing pyrido[1,6-a]imidazophenazine derivatives (4) and/or (8)
respectively.

Synthesis of Some Pyrido-Imidazophenazine Derivatives
1943
CHART 2

1944
A. A. El Bahnasawy and M. F. El Ahwany
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