Synthesis of 1-azabenzo[a]phenoxazin-5-one and 11-amino-1,8,10-triazabenzo[a]phenoxazin-5-one and their Functionalized aryl derivatives via Mizoroki-Heck arylation methodology

Article abstract of DOI:10.13005/ojc/310144

The synthesis of angular 1-azabenzo[a]phenoxazin-5-one and 11-amino-1,8,10-triazabenzo[a] phenoxazin-5-one and their functionalized aryl derivatives via Mizoroki-Heck arylation methodology is reported. 11-Amino-1,8,10-triazabenzo[a]phenoxazin-5-one (16) and 1-azabenzo[a]phenoxazin-5-one (18) were synthesized by the reaction of 7-chloro-5,8-quinolinequinone (obtained by a multistage conversion of 8-hydroxyquinoline) with 4,5-diamino-6-hydroxypyrimidine and 2-aminophenol respectively in the presence of anhydrous sodium acetate. 11-Amino-1,8,10-triazabenzo[a]phenoxazin-5-one and 1-azabenzo[a]phenoxazin-5-one were subjected to Mizoroki-Heck coupling reaction by refluxing with iodobenzene derivatives, using 1,4-bis(diphenylphosphino)butane-palladium(11) chloride as catalyst, 1,4-bis-(2-hydroxy-3,5-ditertbutylbenzyl)piperazine as ligand and methanol as solvent at 60-650C for 4 h to afford in excellent yield aryl derivatives of angular 11-amino-1,8,10-triazabenzo[a]phenoxazin-5-one (19a-c) and 1-azabenzo[a]phenoxazin-5-one (20a-c) respectively. The structures were established by UV/visible, FTIR, proton-NMR and carbon-13 NMR spectral and elemental analysis.

Full text of DOI:10.13005/ojc/310144

ISSN: 0970-020 X
CODEN: OJCHEG
2015, Vol. 31, No. (1):
Pg. 371-378
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
www.orientjchem.org
Synthesis of 1-azabenzo[a]phenoxazin-5-one and
11-amino-1,8,10-triazabenzo[a]phenoxazin-5-one and
their Functionalized Aryl Derivatives via Mizoroki-Heck
Arylation Methodology
TIMOTHY TOBAONI, UCHECHUKWU CHRIS OKORO and DAVID IZUCHUKWU UGWU
Department of Pure and Industrial Chemistry, University of Nigeria, Nsukka, Nigeria.
*Corresponding author: izuchukwu.ugwu@unn.edu.ng
http://dx.doi.org/10.13005/ojc/310144
(Received: November 25, 2014; Accepted: January 10, 2015)
ABSTRACT
The synthesis of angular 1-azabenzo[a]phenoxazin-5-one and 11-amino-1,8,10-
triazabenzo[a] phenoxazin-5-one and their functionalized aryl derivatives via Mizoroki-Heck
arylation methodology is reported. 11-Amino-1,8,10-triazabenzo[a]phenoxazin-5-one (16) and 1-
azabenzo[a]phenoxazin-5-one (18) were synthesized by the reaction of 7-chloro-5,8-
quinolinequinone (obtained by a multistage conversion of 8-hydroxyquinoline) with 4,5-diamino-6-
hydroxypyrimidine and 2-aminophenol respectively in the presence of anhydrous sodium acetate.
11-Amino-1,8,10-triazabenzo[a]phenoxazin-5-one and 1-azabenzo[a]phenoxazin-5-one were
subjected to Mizoroki-Heck coupling reaction by refluxing with iodobenzene derivatives, using
1,4-bis(diphenylphosphino)butane-palladium(11) chloride as catalyst, 1,4-bis-(2-hydroxy-3,5-ditert-
butylbenzyl)piperazine as ligand and methanol as solvent at 60-650C for 4 h to afford in excellent
yield aryl derivatives of angular 11-amino-1,8,10-triazabenzo[a]phenoxazin-5-one (19a-c) and 1-
azabenzo[a]phenoxazin-5-one (20a-c) respectively. The structures were established by UV/
visible, FTIR, proton-NMR and carbon-13 NMR spectral and elemental analysis.
Key words: 1-azaphenoxazinone, 1,8,10-triazaphenoxazinobe, Mizoroki-Heck, arylation, synthesis.
INTRODUCTION
Among the several industrial applications of
phenoxazine derivatives are their use as acid-base
indicator7, biological stains8, laser dyes9 and
chromophoric compounds10 in host guest artificial
protonic antenna systems. Ruan et al11 has reported
phenoxazinone derivatives of antitumour potential
in wild-type and drug resistant tumor cells. Zaytsey
et al12 reported the synthesis of chromogenic
Phenoxazine derivatives are compounds
of great interest because of their several successful
applications as dyes and drugs.They exhibit strong
biological activities ranging from antidepressant1,
anticancer3,
antituberculosis5 and schizophrenia agents6.
antitumour2,
antibacterial4,

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TOBA et al., Orient. J. Chem., Vol. 31(1), 371-378 (2015)
phenoxazinone substrate for -alanyl amino acid (3), the chandrananimycin A or B (4) to mention
peptidase. Abe et al13 has reported the synthesis of but a few. Jeromin17 reported phenoxazine system
2-amino-4,4-dihydro-4,7-dimethyl-3H- derivatives which have been successfully applied
phenoxazin-3-one that could prevent growth of for phenoxyl radical stabilization. Thimmaiah et al18
human lung carcinoma cells and induce apoptosis. reported the synthesis of series of N10-substituted
Gerasimova et al14 reported the synthesis of phenoxazines with Akt inhibitory potential. The
fluorinated benzophenoxazines via sequential SNAr structural modifications of parent phenoxazine ring
substitution reactions of fluorinated aromatics. Jose were borne out of the need to minimize their
and Burgess15 has also reported the synthesis of undesirable effect and at the same time enhance
benzophenoxazine based fluorescent dyes used the biological activities. Angular phenoxazines are
for labeling biomolecules. Carr et al16 reported phenoxazine derivatives that have non-linear
plectosphaeroic acid, a marine fungal natural arrangement of the ring system. Few examples of
product containing phenoxazine ring as inhibitor of angular phenoxazine derivatives includes dibenzo
indoleamine
2,3-dioxygenase.
Amino [a,i] phenoxazine (5), dibenzo[a,j] phenoxazine (6),
phenoxazinone core has also been reported in dibenzo[a,h]phenoxazine (7) and benzopyranol
numbers of bioactive substances such as [3,4-b] benzoxazine (8) in which one of the ring
exfoliazone (1), the venezuelines (2), cinnabarinic carbon atom was replaced with oxygen.
R
O
COOH
NH2
CH3
N
NHAc
PrCOO
N
NHAc
O
RO
N
O
NH2
O
N
N
O
H
O
O
O
1
O
4
2
3
H
N
H
N
H
N
H
N
O
O
O
O
5
O
8
7
6
EXPERIMENTAL
were of technical grade and were purchased from
Aldrich in sure-seal bottles and were used without
Reactions were carried out under nitrogen further purifications.
atmosphere where necessary. Melting points were
determined with a Fischer Johns melting point Synthesis of 8-hydroxy-5-nitrosoquinoline
apparatus and are uncorrected. UV/ visible spectra hydrochloride (10)
were recorded in acetone on a Unicon UV- 2500PC
The method of Pratt and Drake19 was used
spectrophotometer using matched 1cm quartz cells, to synthesize this compound. Into a liter beaker
absorptions were measured in nanometer (nm). IR placed in an ice bath, a solution of 8-
spectra were recorded on 8400s Fourier Transform hydroxyquinoline (9) (58 g, 0.4 mol) and water (200
Infrared (FTIR) spectrophotometer and are reported mL) was poured in, concentrated hydrochloric acid
in wave numbers (cm-1). UV/visible and IR spectral (75 mL) and ice (200 g) was added. Aqueous
analysis were done at the National Research solution of sodium nitrite (NaNO2) (30 g) in water
Institute for Chemical Technology (NARICT), Zaria, (100 mL) was added in portions to the mixture with
Kaduna State, Nigeria. Nuclear magnetic resonance vigorous stirring for over 1 h at 0-4 °C. The mixture
(1H NMR and 13C NMR) spectra were obtained using was allowed to stand overnight at 0°C and the
a Jeol 400MHz spectrometer at Strathclyde desired product filtered and washed with cold water.
University, Scotland. Chemical shifts are reported The product was air dried to afford a bright yellow
in () scale. The elemental analysis was done on a solid. Yield 8.2 g, (92%), mp 181 °C.
Heraeus CHN-O rapid analyzer. All reagents used

TOBA et al., Orient. J. Chem., Vol. 31(1), 371-378 (2015)
373
Synthesis of 8-hydroxy-5-nitroquinoline (11)
The oxidation of 8-hydroxy-5-
water (280 mL) into a litre three necked round
bottom flask equipped with a long magnetic stirring
bar. The mixture was heated in a water bath at 50
°C with vigorous stirring and potassium hydroxide
(8 M, 70 mL) was added while heating continued.
The mixture was treated with sodium dithionate (70
g). The mixture was reheated; maintained at 80 °C
for 10 min while a rapid stream of nitrogen gas was
passed into the flask. After 10 min, more sodium
dithionate (10 g) was added while the passage of
nitrogen gas continued for another 10 min. The
resulting suspension was cooled in ice under
nitrogen gas and the precipitate filtered off by
suction, washed with cold water containing trace of
dithionate and dried rapidly in an oven to give 5-
amino-7-chloro-8-hydroxyquinoline as a golden
yellow solid.Yield 22.0 g (98 %), mp 171-172 °C (lit
173-174 °C)20.
nitrosoquinoline (10) to 8-hydroxy-5-nitroquinoline
(11) was carried out according to the procedure of
Petrow and Sturgeon20. Finely grounded 8-hydroxy-
5-nitrosoquinoline hydrochloride (10) (15.0 g, 0.7
mmol) was added into a 500 mL beaker containing
concentrated nitric acid (45 mL) and water (30 mL)
in an ice bath. The mixture was stirred for 85 min at
17 °C. Equal volume of cold water was added and
the mixture cooled to 0 °C and alkaline was made
with cold concentrated potassium hydroxide
solution pH 13.0. The red potassium salt was
decomposed on neutralization with acetic acid,
filtered by suction and washed with water. The
residue was recrystallized from ethanol to afford a
bright yellow crystal of 8-hydroxy-5-nitroquinoline.
Yield 14.10 g (90.1%), mp 179 °C (lit 179.5-181.5
°C)20.
7-Chloro-5,8-quinolinequinone (14)
Synthesis of 7-chloro-8-hydroxy-5-nitroquinoline
(12)
7-Chloro-5,8-quinolinequinone (14) was
synthesized by suspending 5-amino-7-chloro-8-
hydroxyquinoline (13) (22.4 g, 0.1 mol) in water
(600 mL) in a litre beaker equipped with a long
magnetic stirring bar in an ice-salt bath. Sulphuric
acid (6 M, 18 mL) was added to dissolve the amine,
while vigorous stirring continued, the solution was
cooled to 2 °C and the salt precipitated out in a
finely divided form. An ice-cold solution made of
potassium dichromate (10%, 103 mL) and sulphuric
acid (6 M, 71 mL) was then added.The mixture was
stirred and cooled in the ice-salt bath for 15 min.
The precipitated salt was filtered in cold Buckner
funnel containing trace of ice, washed with cold
water and air dried to afford a light tan residue which
was recrystallized from aqueous dimethyl
formamide (DMF) to obtain 7-Chloro-5,8-
quinolinequinone as a bright yellow solid. Yield
22.2 g (99%), mp 172-173 °C (lit 173.5-174.5 °C)20.
The chlorination of 8-hydroxy-5-
nitroquinoline (11) was achieved using the
literature20. 8-Hydroxy-5-nitroquinoline (11) (10 g)
was suspended in water (1 L) in a two liter beaker
and potassium hydroxide (1 M, 45 mL) was added.
The mixture was stirred vigorously as sodium
hypochlorite (72 mL) was added in portion for 90
min. After the addition of the hypochlorite, the mixture
was stirred for further 2 h, neutralized with acetic
acid and stirred to ensure complete conversion of
the precipitate to free quinolinol. The mixture was
then filtered and washed with water and the residue
recrystallized from aqueous ethyl acetate to afford
7-chloro-8-hydroxy-5-nitroquinoline as a bright
orange solid. Yield 8.50 g, (88%), mp 233-234 °C
(lit 235 °C)20.The presence of the chloro group was
confirmed using sodium fusion21.
Synthesis of 5-amino-7-chloro-8-hydroxy-5-
nitroquinoline (13)
Synthesis of 11-amino-1,8,10-triazabenzo[a]
phenoxazin-5-one (16)
The reduction of 7-chloro-8-hydroxy-5-
4,5-Diamino-6-hydroxypyrimidine (15)
nitroquinoline (12) to 5-amino-7-chloro-8-hydroxy-
5-nitroquinoline (13) was achieved using the
literature20. 7-Chloro-8-hydroxy-5-nitroquinoline
(12) (22.4 g, 0.1 mmol) was ground in a mortar with
potassium hydroxide (1 M, 110 mL) to ensure
complete reduction of the insoluble potassium salt.
The suspension was transferred with the aid of
(0.6 g, 0.005 mol), sodium acetate (1 g, 0.01 mol)
and benzene (40 mL) mixed with DMF (5 mL) were
charged into a 100 mL three necked round bottom
flask fitted with short magnetic stirring bar and a
reflux condenser. The mixture was stirred while
heating on a water bath at 65-75 °C for 45 min. 7-
Chloro-5,8-quinolinequinone (14) (0.9 g, 0.005

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TOBA et al., Orient. J. Chem., Vol. 31(1), 371-378 (2015)
mol) was added and the stirring continued with Synthesis of 11-amino-1,8,10-triazabenzo[a]
heating at 70-75 °C for 8 h.The colour of the reaction phenoxazin-5-one angular derivatives (19a-c)
mixture changed from light brown to greenish yellow,
In a two necked round bottom flask 0.5 g of
to red and intense red as the reaction progressed. 1,4-bis(2-hydroxy-3,5-di-tert-butylphenyl)
After 8 h, the reaction mixture was filtered and the piperazine ligand, 0.5 g of 1,4-bis(diphenyl
solvent allowed to evaporate to afford 11-amino- phosphino)butane palladium(II) chloride catalyst
1,8,10-triazabenzo[a]phenoxazin-5-one (16) as and 5 mL of methanol were placed with a magnetic
intense reddish crystals. Yield 1.36 g, (90%), mp stirring bar.After stirring for 5 min, 11-Amino-1,8,10-
287 °C. UV/vis (acetone max): 321.6 (log e 1.8135), triazabenzo[a]phenoxazin-5-one (16) (1.3 g, 0.005
433.6 (log e 2.4450). FTIR (KBr, v, cm-1):3420, 3289 mol), iodobenzene derivatives (0.005 mol) and
(NH), 3090 (C-H aromatic), 1701 (C=O), 1630, 1603, potassium carbonate (0.8 g) were added to the
1570 (C=N), 1478 (C=C), 1245 (C-O), 1091 (C-N). reaction flask. Stirring continued while heating on a
1H NMR (DMSO-d6, 400MHz) : 7.2 (2H, d, J=8.90 water bath at 60-65 °C for 4 h. The colour of the
Hz, Ar-H), 7.0 (1H, t, J= 7.09 Hz, Ar-H), 6.4 (1H, s, reaction mixture changes from pinkish red to
Ar-H), 6.3 (1H, s, 6-H), 5.4 (1H, s, NH2). 13C NMR yellowish red and intense yellow as the reaction
(DMSO-d6, 400MHz) : 165.40, 164.93, 162.34, progressed. After 4 h, the reaction mixture was
162.09, 159.90, 132.97, 132.08, 129.84, 127.29, filtered and the filtrate allowed to evaporate to
127.21, 122.04, 118.56, 110.67. C13H7N5O2 obtain the 11-amino-1,8,10-triazabenzo[a]
Calculated: C, 58.87, H, 2.66, N, 26.41, O, 12.06, phenoxazin-5-one angular derivatives in good to
found: C, 58.80, H, 2.70, N, 26.50, O, 12.02
excellent yield.
Synthesis of 1-azabenzo[a]phenoxazin-5-one (18) 6-(2-Carboxyphenyl)-11-amino-1,8,10-
2-Aminophenol (17) (0.5 g, 0.005 mmol), triazabenzo[a]phenoxazin-5-one angular
sodium acetate (1 g, 0.01 mol) and benzene (40 mL) derivative (19a)
mixed with dimethyl formamide (5 mL) were charged
The compound was intense yellow, yield
into a 100 mL three necked round bottom flask fitted 0.7 g (56%), mp 295 °C. UV/vis (acetone) lmax: 322
with a magnetic stirring bar and a reflux condenser. (log e 1.8158), 436 (loge 2.4587), 496.2 (log
The mixture was stirred while heating on a water bath 2.7981), 546.4 (loge 3.0812). FTIR (KBr, v, cm-1):
1
at 70-75 ºC for 45 min. 7-Chloro-5,8-quinolinequinone 3467 (NH), 1628 (C=O), 1281 (C-O). H NMR
(14) (0.9 g, 0.005 mol) was added and the stirring (DMSO-d6, 400MHz) : 7.8 (4H, m, Ar-H), 6.9 (1H, s,
continued with heating at 70-75 °C for 8 h. The colour Ar-H), 6.1 (3H, m, Ar-H), 5.8 (2H, s, NH2). 13C NMR
of the reaction mixture changed from yellowish ash to (DMSO-d6, 400MHz) : 171.09, 167.05, 162.89,
brown, to reddish brown and intense pinkish brown 162.01, 160.32, 159.80, 142.01, 140.90, 140.34,
as the reaction progressed. After 8 h, the reaction 132.21, 132.10, 130.98, 130.05, 130.01, 128.92,
mixture was filtered and the solvent evaporated from 128.41, 125.55, 124.59, 124.07, 121.95. C20H11N5O4
the filtrate to give 1-azabenzo[a]phenoxazin-5-one as calculated: C, 62.34, H, 2.88, N, 18.17, O, 16.61,
intense brown solid. Yield 1.16 g, (87%), mp 272 °C. found: C, 62.30, H, 2.90, N, 18.16, O, 16.61
UV/vis (acetone)max: 321.4 (log e 1.8124), 436.8 (log
e 2.4632). FTIR (KBr, v, cm-1): 2932 (C-H aromatic), 6 - ( 4 - n i t r o p h e n y l ) - 11 - a m i n o - 1 , 8 , 1 0 -
1586, 1583 (2C=N), 1488 (C=C), 1387, 1301 (2C-O), triazabenzo[a]phenoxazin-5-one angular
1
1163 (C-N), 815, 752 (substitution in benzene). H derivative (19b)
NMR (DMSO-d6, 400MHz) : 7.6 (m, 4H, Ar-H), 7.2 (m,
The compound was brownish in colour,
3H, Ar-H), 6.3 (1H, s, Ar-H). 13C NMR (DMSO-d6, yield 1.0 g (87 %), mp 301 °C. UV/vis (acetone) max
:
400MHz) : 167.87, 159.98, 158.75, 145.65, 140.44, 326.6 (loge 1.8417), 360 (loge 2.0301), 397.4 (loge
129.43, 128.90, 128.32, 125.76, 122.32, 121.98, 2.2410), 497 (loge 2.8027), 654.6 (loge 3.6914).
121.09, 120.08, 120.01, 117.68. C15H8N2O2 calculated: FTIR (KBr, v, cm-1): 3366, 3258 (2NH), 3092 (C-H
C, 72.58, H, 3.25, N, 11.28, O, 12.89, found: C, 72.60, aromatic), 1710 (C=O), 1589 (C=N), 1494 (C=C),
H, 3.20, N, 11.30, O, 12.90. The iodobenzene 1291 (C-O), 1169, 1094 (C-N), 841, 750 (substitution
1
derivatives were prepared according to the method of in benzene). H NMR (DMSO-d6, 400MHz) : 7.2
Williamson22.
(2H, d, J= 8.23 Hz, Ar-H), 7.0 (2H, d, J= 7.89 Hz, Ar-

TOBA et al., Orient. J. Chem., Vol. 31(1), 371-378 (2015)
375
H), 6.7 (3H, m, Ar-H), 6.2 (1H, s, Ar-H). 13C NMR
(DMSO-d6, 400MHz) : 165.98, 162.09, 161.78,
160.60, 159.89, 159.09, 150.76, 150.53, 138.85,
135.32, 133.22, 133.01, 131.33, 130.92, 128.57,
127.06, 123.09, 120.70, 118.02. C19H10N6O4
calculated: C, 59.07, H, 2.61, N, 21.75, O, 16.57,
found: C, 59.00, H, 2.60, N, 21.80, O, 16.60.
6-(2-carboxyphenyl)-1-azabenzo[a]phenoxazin-
5-one angular derivative (20a)
The compound was yellow in colour, yield
0.9 g (87%), mp 307 °C. UV/vis (acetone) max: 321.2
(loge 1.8113), 360 (loge 2.4722), 438.4 (loge
2.8162), 544.2 (loge 3.0688), 656 (loge 3.7004).
FTIR (KBr, v, cm-1): 3473 (broad, OH), 2980 (C-H
aromatic), 1576 (C=N), 1480 (C=C), 1288 (C-O),
1127 (C-N), 746 (substitution in benzene). 1H NMR
(DMSO-d6, 400MHz) : 7.3 (m, 4H, Ar-H), 6.8 (3H,
m, Ar-H), 6.1 (4H, m, Ar-H). 13C NMR (DMSO-d6,
400MHz) : 171.00, 162.89, 155.80, 150.85, 145.01,
142.00, 140.84, 130.20, 128.41, 128.01, 126.67,
125.85, 125.59, 124.70, 123.95, 123.56, 123.05,
120.89, 120.45, 119.03, 117.65, 115.54.
C22H12N2O4 calculated: C, 71.74, H, 3.28, N, 7.61,
O, 17.37, found: C, 71.80, H, 3.30, N, 7.60, O, 17.30.
6-(4-hydroxyphenyl)-11-amino-1,8,10-
triazabenzo[a]phenoxazin-5-one angular
derivative (19c)
The compound was coloured ash, yield
0.7 g (78%), mp 320 °C. UV/vis (acetone) max: 326.6
(loge 1.8417), 440.6 (loge 2.4846), 503.2 (loge
2.8376), 654.6 (loge 3.6914). FTIR (KBr, v, cm-1):
3584, 3299 (2NH), 2941 (C-H aromatic), 1690
(C=O), 1589 (C=N), 1483 (C=C), 1303 (C-O), 1125
(C-N), 817, 759 (substitution in benzene). 1H NMR
(DMSO-d6, 400MHz) : 7.1 (4H, m, Ar-H), 6.6 (3H,
m, Ar-H), 6.3 (2H, d, J=7.82 Hz, Ar-H), 6.1 (2H, d, J=
8.23 Hz, Ar-H). 13C NMR (DMSO-d6, 400MHz)
:162.21, 160.08, 159.90, 154.34, 150.97, 137.60,
137.21, 132.45, 132.12, 129.87, 129.09, 126.32,
126.08, 122.96, 122.23, 120.09, 117.07, 115.76,
115.02. C19H11N5O3 calculated: C, 63.86, H, 3.10,
N, 19.60, O, 13.43, found: C, 63.90, H, 3.00, N,
19.58, O, 13.40
6-(4-nitrophenyl)-1-azabenzo[a]phenoxazin-5-
one angular derivative (20b)
The compound was intense yellowish in
colour, yield 1.1 g, (98%), mp 300 °C. UV/vis
(acetone) max: 321.6 (loge 1.8135), 360 (loge
2.2151), 392.8 (loge 2.8117), 498.6 (log 3.0812),
655.4 (loge 3.6959). FTIR (KBr, v, cm-1): 3100 (C-H
1
aromatic), 1627 (C=O), 1282 (C-O). H NMR
(DMSO-d6, 400MHz) : 7.9 (2H, d, J= 9.04 Hz, Ar-
H), 7.0 (2H, d, J= 6.89 Hz, Ar-H), 6.5 (3H, m, Ar-H),
6.1 (4H, m, Ar-H). 13C NMR (DMSO-d6, 400MHz) :
169.11, 167.25, 160.22, 159.88, 132.23, 132.01,
130.88, 130.15, 130.06, 128.99, 128.11, 125.45,
124.99, 124.17, 121.55, 120.89, 120.04, 118.98,
116.27, 115.70, 110.01. C21H11N3O4 calculated: C,
68.29, H, 3.00, N, 11.38, O, 17.33, found: C, 68.30,
H, 3.00, N, 11.36, O, 17.32
Synthesis of 1-azabenzo[a]phenoxazin-5-one
angular derivatives (20a-c)
Into a two necked round bottom flask
equipped with magnetic stirring bar, the mixture of
1,4-bis(2-hydroxy-3,5-di-tert-butylbenzyl)
piperazine
ligand
(0.5
g),
1,4-bis
(diphenylphosphino)butane palladium(II) chloride
catalyst (0.5 g) and methanol (5 mL) were placed.
After stirring for 5 min, 1-azabenzo[a] phenoxazin-
5-one (18) (1.2 g, 0.005 mol), iodobenzene
derivatives (0.005 mol) and potassium carbonate
(0.8 g) were added to the reaction mixture, stirring
continued while heating on a water bath at 60-65
°C for 4 h, the colour of the reaction mixture changes
from pinkish red to yellowish red and intense yellow
as the reaction progressed. After 4 h, the reaction
mixture was filtered and the filtrate was allowed to
evaporate to dryness before extracting the product
with acetone. The acetone extract was allowed to
evaporate to obtain 1-azabenzo[a]phenoxazin-5-
one angular derivatives in excellent yield.
6-(4-hydroxyphenyl)-1-azabenzo[a]phenoxazin-
5-one angular derivative (20c)
The compound was ash in colour, yield
0.8 g (87%),mp 330 °C. UV/vis (acetone) max: 321.8
(loge 1.8147), 437.6 (loge 2.4677), 498.4 (loge
2.8105).FTIR (KBr, v, cm-1):3436 (broad, OH), 2935
(C-H aromatic), 1581 (C=N), 1486 (C=C), 1288 (C-
O), 1164 (C-N), 838, 758 (substitution in benzene).
1H NMR (DMSO-d6, 400MHz) : 6.9 (2H, d, J= 8.74
Hz, Ar-H), 6.6 (2H, d, J= 7.88 Hz, Ar-H), 6.5 (2H, d,
J= 8.93 Hz, Ar-H), 6.3 (1H, t, J= 8.04 Hz, Ar-H), 6.1
(4H, m, Ar-H). 13C NMR (DMSO-d6, 400MHz) :
165.55, 159.22, 158.28, 132.32, 132.11, 130.88,
130.15, 128.90, 128.14, 125.44, 124.49, 124.18,

376
TOBA et al., Orient. J. Chem., Vol. 31(1), 371-378 (2015)
121.65, 120.88, 120.14, 118.78, 116.36, 115.08, and 7-chloro-5,8-quinolinequinone (14) in the
112.98, 112.09, 110.02. C21H12N2O3 calculated: C, presence of sodium acetate at 70-75 °C for 8 h using
74.11, H, 3.55, N, 8.23, O, 14.10, found: C, 74.10, H, benzene/dimethyl formamide as solvent (scheme
3.52, N, 8.20, O, 14.15
2). The reaction of 11-amino-1,8,10-triazabenzo
[a]phenoxazin-5-one (16) with iodobenzene
derivatives in the presence of 1,4-bis(2-hydroxy-
3,5-di-tert-butylbenzyl)piperazine as ligand, 1,4-
RESULTAND DISCUSSION
The synthesis of 1-azabenzo[a] bis(diphenylphosphino)butane palladium(II)
phenoxazin-5-one (18) was achieved by the chloride as catalyst, methanol as solvent and
reaction of 2-aminophenol (17) and 7-chloro-5,8- triethylamine as base at 60-65 °C under reflux for 4
quinolinequinone (14) in the presence of sodium h gave the aryl derivatives of angular 11-amino-
acetate at 70-75 °C for 8 h (scheme 2).The reaction 1,8,10-triazabenzo[a]phenoxazin-5-one (19a-c) in
of 1-azabenzo[a]phenoxazin-5-one (18) with excellent yield (scheme 3). The iodobenzene
iodobenzene derivatives in the presence of 1,4- derivatives and 7-chloro-5,8-quinolinequinone
bis(2-hydroxy-3,5-di-tert-butylbenzyl)piperazine as (scheme 1) were prepared according to the
ligand,
1,4-bis(diphenylphosphino)butane literature and their purity ascertained using melting
palladium(II) chloride as catalyst, methanol as point. The synthesized monoaza and
solvent and triethylamine as base at 60-65 °C under triazabenzo[a]phenoxazin-5-ones and their
reflux for 4 h gave the aryl derivatives of angular 1- functionalized derivatives were characterized using
azabenzo[a]phenoxazin-5-one (20a-c) in excellent UV/visible, FTIR, 1H NMR and 13C NMR
yield (scheme 4). 11-Amino-1,8,10-triazabenzo[a] spectroscopies and elemental analysis. The
phenoxazin-5-one (16) was synthesized by the proposed structures of the novel compounds were
reaction of 4,5-diamino-6-hydroxypyrimidine (15) in agreement with spectral and elemental analysis.
NO2
NO
conc HNO3/H2O,
KOH aq, AcOH
NaNO2/conc. HCl,
H2O, 0-4 o
N
C
N+
N
OH
11
OH
10
H Cl-
OH
9
KOH/H2O,
5%NaOCl, AcOH
O
NH2
NO2
KOH, Na2S2O4,
80 oC, AcOH
12 N H2SO4
10% K2Cr2O7
H2O
Cl
N
Cl
N
Cl
N
O
14
OH
OH
13
12
Scheme 1:
NH2
NH2
NH2
OH
N
NH2
N
O
N
OH
N
17
15
N
N
O
NaAc, C6H6/DMF
NaAc, C6H6/DMF
65-75 oC, 8 h
N
65-75 oC, 8 h
O
O
Cl
N
N
O
18
O
16
14
Scheme 2:

TOBA et al., Orient. J. Chem., Vol. 31(1), 371-378 (2015)
377
NH2
N
NH2
N
NH2
N
2-iodobenzoic acid
Pd(dppb)Cl2
4-iodophenol
Pd(dppb)Cl2
N
O
N
O
N
N
N
N
TEA, ligand, solvent
reflux, 4 h
TEA, ligand, solvent
reflux, 4 h
N
O
N
O
N
O
16
O
COOH
H
19a
19c
4-iodo-4-nitrobenzene
Pd(dppb)Cl2
TEA, ligand, solvent
OH
reflux, 4 h
N
NH2
N
N
N
O
O
19b
NO2
Scheme 3:
N
N
N
4-iodophenol
Pd(dppb)Cl2
2-iodobenzoic acid
Pd(dppb)Cl2
N
O
N
O
N
TEA, ligand, solvent
reflux, 4 h
TEA, ligand, solvent
reflux, 4 h
O
O
O
O
COOH
18
H
4-iodo-4-nitrobenzene
Pd(dppb)Cl2
20a
20c
TEA, ligand, solvent
reflux, 4 h
OH
N
N
O
O
20b
NO2
Scheme 4:
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