supervisor: dr. u.c. okoro february 2012 - … alifa.pdf · · 2015-09-16the first synthetic...
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1
i
DEPARTMENT OF PURE AND INDUSTRIAL CHEMISTRY
FACULTY OF PHYSICAL SCIENCES
UNIVERSITY OF NIGERIA, NSUKKA
RESEARCH PROJECT (CHEM 581)
RAPID ACCESS TO 11-(N-SUBSTITUTED) - ANGULAR
TRIAZAPHENOXAZINONE VIA COPPER CATALYZED N-ARYLATION
REACTION
A RESEARCH PROJECT SUBMITTED IN PARTIAL FULFILLMENT OF
THE REQUIREMENT FOR THE AWARD OF MASTERS OF
SCIENCE (M.Sc) DEGREE IN ORGANIC CHEMISTRY
BY
JACOB, ALIFA DAVID
PG/M.Sc/08/49858
SUPERVISOR: DR. U.C. OKORO
FEBRUARY 2012 CHA
2
PTER ONE
1.0 INTRODUCTION
Phenoxazines are tricyclic heterocycles consisting of two benzene rings fused to an
oxazine structure1.
N
O
N
O
H
1a 1b
They are found in the actinomycins2, in various insect pigments called ommochromes
3,
and in some microorganism metabolites4. Chemically, they can be synthesized by
oxidative condensation of o-aminophenol and its derivatives5.
Phenoxazines are very useful compounds, which form the nuclei of several other
important compounds. Phenoxazine derivatives have been used as drugs, colourant in
textile industries among others. Their pharmacological activities span a wide spectrum as
sedatives, tranquilizers, antiepileptic, central nervous system depressant, anti-tumor,
antibacterial to mention but a few. They also show some usefulness as laser dyes,
antioxidants, and biological stain6.
Angular Phenoxazine, derivatives with highly improved biological activities have
been synthesized7. In view of this, several molecular modifications have been carried out
on phenoxazine ring, among which are benzo[a]phenoxazine 28 and benzo[c]phenoxazine
39.
3
N
O
H
N
O
H
2 3
As a further variation in the structure of phenoxazine, the first three-branched
phenoxazine of the type 4 was reported by Okafor and Okoro10
O
N
O
N
4
Owing to the quest for aza analogues of angular phenoxazines, Okafor11
also
reported the synthesis of the first three branched benzoxazinophenothiazine ring system
of type 5, 6 and 7
O
N
S
N
O
N
O
NN
N
N
5 6
4
O
N
O
N
N
2N
7
Okafor and co worker12
also reported the successful synthesis of Y-shaped
structure of mono and diazabenzothiazinophenoxazine ring system of the type 8 and 9
8 9
In a recent development, Okoro et al13
reported the synthesis of the first angular
triazaphenoxazine of type 10.
NH2
N
N O
N
N
O
10
O
N
S
N
O
N
O
N
2 N
N
5
In view of the current interest in the synthesis of the derivatives of angular
triazaphenoxazine ring system, we therefore report the successful synthesis of 11-
phenylamino-1, 8, 10-triazabenzo[a]phenoxazin-5-one 11 and its 4-bromophenylamino
12, 3-chlorophenylamino 13 and 3-nitrophenyl amino 14 derivatives.
N
N O
N
NN
O
N
N O
N
NN
O
HHBr
11 12
N
N O
N
NN
O
N
N O
N
NN
O
O2N
HH
Cl
13 14
6
CHAPTER 2
2.0 LITERATURE REVIEW
2.1 Phenoxazines
Phenoxazines are heterocyclic compounds in which two benzene rings are ortho-
fused to a six membered 1, 4-diheteromonocyclic ring containing two heteroatoms,
oxygen, and nitrogen, with molecular formula C12H9NO, and molecular weight 183.21g,
melting at 154-159°C14
.
N
O
N
O
H
1a 1b
The synthesis of phenoxazine has been reported by earlier workers, Kehrmann and
Saager15
, while investigating the reaction of diiodides/dibromides of heterocyclic tertiary
bases in the laboratory. They were able to synthesize phenoxazine by the condensation of
o-aminophenol with the diiodides/dibromides of the heterocyclic tertiary bases.
2.2 Non-Linear (Angular) Phenoxazines
The first synthetic non-linear phenoxazine, benzo[a]phenoxazine 17 was reported
in 1919 by Goldstein and Semelitch16
; the compound was obtained by heating a mixture
of 2-aminophenol 15 and 1-amino-2-naphthol hydrochloride 16 at a temperature of
260°C
7
OH
NH2 H
3N
OH O
N
H
+
Heat
260o
+
15 16 17
Jose and Burgess17
reported the synthesis of two other non-linear phenoxazines, the
Nile Red 22 and Meldola‟s Blue 20. The synthesis of Meldola‟s Blue involved the
condensation of a nitroso compound 18 with 2-naphthol 19 at elevated temperatures,
while the synthesis of Nile Red 22 involved a condensation reaction of nitrosophenol 21
and 2-naphthol 19.
OH O
N
Me2N
Me2N
NO
CH3COOH
+1100 Cl +
18 19 20
Nile Red 22 was also prepare via hydrolysis of Nile blue 23; as shown below
OH
OEt
2N O
N
OHEt2N
NO
CH3COOH
70 o C,1hr
+
21 19 22 10%
8
Et2N O
N
NH2
OEt2N O
NH2SO
4
reflux, 2hr
Nile Blue
+
0.5%
Cl-
23 22 22%
Jose18
reported the synthesis of several derivatives of benzophenoxazines which
included sulfonated benzophenoxazines 26 and 27 from 3, 6-disulfonic acid 25 and 1, 3-
disulfonic acid, 28 respectively.
HO3S SO
3H
OH
O
N
SO3H
SO3H
Me2N
NH2
Me2N
H
NaOAc
Water+
24 25 26
K O3S
SO3 K
OH
O
N
Me2N
SO3KKO
3S
Me2N
NOH
Water++ -
- +
18 28 27
Jose also reported the synthesis of 6-carboxy ethyl derivatives of Nile Red 30, by the
condensation reaction between 4-dialkylaminonitrobenzene 19 and 6-hydroxyethyl
derivative of dihydroxynaphthalene 29 under reflux with ethanol for 3 hours.
9
OH
COOC2H
5
OH
NO
NR
RR
RO
COOC2H
5
O
N
N
Ethanol, reflux+
3 hr
1
2
1
2
18 29 30 24-60%
R1, R
2 = H and simple linear alkyl.
In the same work, Jiney Jose further reported the synthesis of 1-hydroxy 32 and 2-
hydroxy Nile Red 34, which were achieved by reacting 5-diethylamino-2-nitrophenol 21
with 1, 4-dihydroxynaphthalene 31 and 1, 5- dihydroxynaphthalene 33 respectively under
reflux with DMF.
OH
OH
NO
Et2N OH
Et2N OO
N
OH
DMF, Reflux+4 hr
21 31 32 70%
OH
OH
NO
Et2N OH
Et2N OO
N
OH
DMF, Reflux+5 hr
21 33 34 65%
Jose18
also reported the synthesis of 6-fluoro Nile Red 39 from diethylaminephenol 35
and tetrafluoronaphthalene 36 and FLASH dyes based on Nile Red 44, with 2-amino-5-
nitrophenol 40 and 1-hydroxynaphthoquinone 41 as starting materials.
10
F
F
F
FO
F
Et2N
F
F
OHEt2N
NaOH, Pyridine+1000C, 6hr
35 36 37 43%
NaNO2, H
2SO
4)
O2, H
2O,
HCl, Zinc dust
C6H
6,
O
O
F
N
OEt2N O
F
N
OEt2N
400C, 1hr
i
ii) 65%,1hr 250C, 3hr
-
+
. 38 39 43%
OH
O
O
NH2
OHO2N OO
N
O2N
AcOH
+80%
1000C, 12hr
40 41 42 8%
PdH2/C
MeOHNH
2OO
N Hg(OAc)2
AcOH,
HgAOcHgAOc
OO
N
NH2
500C
22 46% 43
11
AsCl3, Pd(OAc)
2, DIEA
NMP,
EDT, acetone,
SAs
S SAs
S
NH2
OO
N250C 12hr
250C 12hr
44 7%
There have been several reports on the synthesis of aza derivatives of non-linear
(angular) phenoxazines. Noelting19
reported the synthesis 5-hydroxypyrido[3,2-
a]phenoxazine, 47 obtained by heating a mixture of 8-hydroxyquinoline 46 and 2-
hydroxy-N,N-dimethylaniline, 45 in ethanol, in the presence of zinc dust.
N
OH
O
N N
OH
NMe2
OH
C2H
5OH/Zn dust+
+
45 46 47a
O
N N
O
47b
12
Ishii20
reported the synthesis of pyrido[3, 2-a]phenoxazine, 49, via a catalyzed
condensation of 2-aminophenol 15 and 4, 6-dihyroxyquinoline-5,8-dione 48 in the
presence of 80% acetic acid.
N
O
OH
OH O
HOOC O
N N
O
OH COOH
OH
NH2
AcOH+
15 48 49
Okafor and co workers21
reported the synthesis of 6-chlorobenzo[a]-11-
azaphenoxazine-5-one 52, by refluxing a mixture of 2-amino-3-pyridinol 50 and 2, 3-
dichloro-1, 4-naphthoquinone 51 in the presence of anhydrous sodium carbonate and
chloroform.
N
OH
NH2
Cl
N
O
N
OCl
Cl
O
O
NaCO3/CHCl
3+
50 51 52
Agarwal and Schafer22
also
reported the synthesis of 6-chlorobenzo[a]-11-
azaphenoxazine-5-one 52 by refluxing a mixture of 2-amino-3-pyridinol 50 and 2, 3-
dichloro-1, 4-naphthoquinone 51 in methanol in the presence of potassium acetate
13
N
OH
NH2
Cl
N
O
N
OCl
Cl
O
O
MeOH/AcOK+
50 51 52
Nanya and coworker23
reported the synthesis of 1, 6- and 4, 6-disubstituted-11-aza-
5H-benzo[a]phenoxazine, 54 which they accomplished by the condensation of 2-amino-
3-hydroxypyridine 50 with 5-substituted-2, 3-dihalogeno-1, 4-naphthoquinone 53 in
benzene/ethanol solvent, in the presence of potassium acetate.
N
OH
NH2
X
N
O
N
O
R
R
X
X
O
O
R
R
C6H
6/DMF
AcOk+
1 1
2
2
50 53 54
X= Halogen, R1 and R2 = H
Hayakawa and coworker24
also reported the synthesis of 6-substituted-11-aza-5H-
pyrido[2,3-a]phenoxazine-5-one 56 and 6-substituted-11-aza-5H-pyrido[3,2-
a]phenoxazine-5-one 57 by, the condensation reaction of 2-amino-3-hydroxypyridine 50
with 6,7-dibromo-5,8-dioxoquinoline 56 in benzene/ethanol in the presence of potassium
acetate at room temperature.
14
N
OH
NH2
N
O
N
O
R
Br
Br
O
O
Br
R
KOAc
C6H
6/C
2H
5OH
RN
O
N
O
Br
+
56
++
50 55 57
Okoro et al25
reported the synthesis of 1, 11-diazabenzo[a]phenoxazin-5-one 59;
which they achieved by the condensation reaction between 2-amino-3-hydroxy-pyridine
50 and 7-chloro-5,8-quinolinequinone 58 in the presence of anhydrous sodium acetate
and a mixture of benzene/DMF as solvent under reflux for 6hrs.
N
OH
NH2 N
O
N
O
N
NCl
O
O
C6H
6/DMF
NaOAc
+
50 58 59
They also reported the synthesis of 11-amino-1, 8, 10-triazabenzo[a]phenoxazin-5-one
10, which they achieved by the condensation reaction between 4, 5-diamino-6-
hydroxypyrimidine 60 and 7-chloro-5, 8-quinolinequinone 58 in a mixture of
15
benzene/DMF as the solvent and in the presence of anhydrous sodium acetate under
reflux condition for 7hrs.
N
N OH
NH2
NH2
Cl
O
O
N
NaOAc
C6H
6/DMF
NH2
N
N O
N
O
N
+
60 58 10
2.3 COPPER CATALYSED REACTIONS
Copper catalyzed C-N cross-coupling reactions are powerful tools to prepare N-
containing compounds which have high utilities in synthetic, biological, pharmaceutical,
and natural sciences26
.
In 2000, Carl T. Wigal27
reported a copper catalyzed oxidation of benzion 61 to
benzil 65. He reported that benzoin can be oxidized to the benzil using a Cu2+
salt and
ammonium nitrate, the pattern is shown below
benzoin benzil
N2 +
2O, NH
4NO
3 +
2Cu2+ 2Cu+
3H 2H+
Scheme 1: Recycling of copper ion in the benzoin oxidation.
16
In the first redox cycle, benzoin 61 donates an electron to Cu2+
, forming Cu
+ and
benzoin radical cation 62. The benzoin radical cation loses a proton to acetate ion (AcO-),
forming acetic acid (AcOH) and a resonance stabilized radical, 63a and 63b. Another
redox cycle between Cu 2+
and the radical takes place, forming a second Cu+ ion and
cation 64, which loses a proton to another acetate ion to form benzil 65.
C C CC
O
H
OH
O O
H
HCu2+
Cu+
OAc
.
+
-
61 62
C C CC
O O
HO O
H
Cu2+
AcOH
.
.
63a 63b
64 65
Scheme 2: Mechanism for the copper-catalyzed reaction of benzoin 61
C C CC
O O
HO OAcO .
+
-
17
Shintani and Fu28
reported a copper-catalyzed 1, 3-cycloaddition of azomethine
Imines 66 to alkynes 67 using Cu (1).
O
N
N
RH
R
CuI
RR
O
N
N
-
++
5% /5.5% 68
11
66 67 69 96%
Fe
P
Me
Me
MeMe
Me Me
Me
N
O
R
68
R= i-Pr
In an earlier examination of the reaction of azomethine imine 70 with ethyl
propiolate 71 at room temperature, in the absence of a copper catalyst, essentially none of
the target heterocyclic compound 72 was generated, but in the presence of 5% CuI, the
desired 1, 3-dipolar cycloaddition proceeded, affording the product as a single
regioisomer in 88% yield.
18
O
N
N
H Ph
O
N
N
CO2Et
Ph
CO2Et
Catalyst
equiv. Cy2NMe
CH2Cl
2 r.t
-
++
0.5
70 71 72
In 2008, Park and co workers29
observed a notable outcome from the Cu-catalyzed
N-heterocyclic carbene reactions of terminal alkynes 74 with α-aryldiazoesters 73,
leading to indenes 75, representing the first example of Cu-catalyzed formal [3+2]
cycloaddition between the two compounds
O
N2
OMe
O
OMe
MeO
Ar
250C, 30mins+
73 74 75
Ar
Ph CO2Me
(Ar= 4-MeOC6H4) 76
19
Entry Catalyst System Solvent Yield (%)
1 CuCl CH2Cl
2 <1(95)
2 CuCl/AgSbF6 CH
2Cl
2 44(40)
3 Cu(IPr)Cl CH2Cl
2 <1(<1)
4 Cu(IPr)Cl/AgSbF6 CH
2Cl
2 75(14)
5 Cu(IPr)Cl/AgSbF6/NaB(ArF)
4 CH
2Cl
2 90(<1)
6 Cu(IMes)Cl/AgSbF6/NaB(ArF)
4 CH
2Cl
2 48(8)
7 Cu(IPr)Br/AgSbF6/NaB(ArF)
4 CH
2Cl
2 84(10)
8 Cu(IPr)Cl/AgSbF6/NaB(ArF)
4 CH
3CN 41(27)
9 Au(IPr)Cl/AgSbF6/NaB(ArF)
4 CH
2Cl
2 30(10)
Table 1: Optimization of the reaction conditions
NB: Yield outside the parenthesis is for 75 while that in parenthesis is for 76
They reported that when methyl- 2-diazophenylacetate 73 was reacted with (4-
methoxyphenyl) acetylene 74 in the presence of CuCl catalyst, a cyclopropene compound
76 was exclusively obtained (table1, entry1). When cationic copper species was used,
3H-indene-1-carboxylate 75 was produced along with the cyclopropene 76 in similar
ratio (entry 2). Although a copper catalyst alone such as Cu(IPr)Cl [IPr: 1, 3-bis(2,6-
diisopropylphenyl)imidazol-2-ylidene] was ineffective (entry 3), a silver additive
significantly increased conversion and selectivity, giving 75 as a major adduct (entry 4).
20
They also reported that certain additives such as NaB(ArF)4 [ArF: 3,5-
bis(trifluoromethyl] offered further improvement of the reaction efficiency and selectivity
under the mild conditions (entry 5). Catalyst having NHC ligand (NHC: N-heterocyclic
carbene) other than IPr (IPr: 1, 3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) were
less effective (entry 6). Modification of the copper species or change of solvent resulted
in detrimental effects (entry 7-8). In addition, Au(IPr)Cl/AgSbF6/NaB(ArF)
4 catalyst
displayed lower efficiency when compared to that of the corresponding Cu species (entry
9).
Mangold (2008)30
reported a copper catalyzed azide/alkyne cycloaddition
(CuAAC), described in the catalytic cycle
21
below.
N
N
CuLx
CuLx
NR
R
N
N
CuLx
NN R
R
NN N
R H
R
NN N
R CuLx
R
HR
R H
CuLx
CuLxR
N NR
N N
R
N
R
CuLx
RDS
[CuLx]
2
1
67
77
78
82
81
80
79
2
1
H+
2
1
1
H+
1
2+
-
2
1
-
+
1
2
23kcal/mol
1
18kcal/mol
Scheme 3: CuAAC catalytic cycle
2.4 COPPER CATALYSED N-ARYLATION REACTIONS
In 2004, Shimi and co-workers31
, reported the comparative copper-catalyzed N-
arylation reactions of 4-aminoacridine 83 with organobismuth, 84 organoboron 85 and
organolead compounds 86.
22
N
NH2
N
NHPh
N
NPh Ph
PhM, Cu(OAc)2
CH2Cl
2, rt
+
83 87 88
PhM= Ph3Bi (OAc)2 ,84 PhB(OH)2 85 and PhPb(OAc)3 86
They prepared 4-aminoacridine 83 in four steps by Ullmann reaction between
ortho-bromobenzoic acid and orthophenylenediamine, followed by H2SO4 catalyzed
cyclization reduction-dehydration and air oxidation. The reaction of 4-aminoacridine 83
with the phenylating systems led to the corresponding monophenyl 87 and diphenyl 88
derivatives of 4-aminoacridine 83. However, a comparative study with the various
phenylating systems showed a significant difference of reactivity.
In 2005, Chernick Erin and co-workers32
, reported that cyclic imides 90 with six-
membered rings are shown to undergo efficient N-arylation, using arylboronic esters 89
mediated by copper(II)acetate in the presence of an amine base and oxygen atmosphere,
with gentle heating.
RO ORB
R
Cu(OAc)2, NEt
3
CH2Cl
2, O
2
R
N
H
OON OO
1 +4Ams,
89 90 91
This reaction is applicable to the synthesis of new organic materials based on arylene
imide and bis(imide)dyes, such as perylene-3,4:9,10-bis(dicarboximide)s 94 and 95
24
Entry Ester/acid Product Imide/ester/
Cu/base
Temp. (°C) Yield (%)
1
OHPh B
OH
92a
94
1:3:2:3 r.t. 78°
2
O
O
BPh
92b
94
1:3:3:3 55 71
3 O
B
O
Ph
92c
94
1:3:2:3 55 94
4
O
O
BPh
92d
94
1:2:2:3 47 32
5
B
O
O
Ph
92e
94
No reaction
6
O2N B
O
O
92f
95
1:2:2:3 r.t. 43°
Table 2: Variation of arylation coupling partner
25
NB: All reactions above, where carried out for approximately 20hrs, with the exception
of entry 1, which was reacted for 4hrs. 93 is naphthalimide.
Kim and Chang33
reported a copper/ligand-catalysed N-arylation of 4-
iodoacetophenone 96 with NH4Cl. To their delight, the cross-coupling reaction provided
the desired product, 4-aminoacetophenone 97
I
O
NH2
O
Cat.[Cu]ligand
K2CO
3
Solvent,
NH4Cl
12hr
+
96 97
Entry [Cu]cat. Ligand Solvent T/°C Yield(%)
1 CuCl2 L1 DMSO 40 0
2 CuOAc L1 DMSO 40 15
3 CuI L1 DMSO 40 56
4 CuI L2 DMSO 40 60
5 CuI L3 DMSO 40 0
6 CuI L4 DMSO 40 3
26
7 CuI L5 DMSO 40 47
8 CuI L6 DMSO 40 29
9 CuI L2 DMSO 40 20
10 CuI L2 DMSO, H2O
c
40 72
11 CuI L2 DMSO, H2O
c
25 80
Table 3: Cu/ligand-catalyzed N-arylation of 4ʹ-iodoacetophenone with NH4Cl
NH--HN
OHN OH
OH
H HO
OHN
L1 98 L2 99 L3 100 L4 101
OOH
N
O
OHS
L5 102 L6 103
Sorokin34
, reported several N-arylation reactions of azoles via copper(I) catalysis,
using the proposed scheme below.
27
CuIX
HetNH
CuI-NHHet+
Base
Base H+
NHetAr-X
HetN-Ar
CuIII-X
HetN
CuI
Ar
CuIII
.XAr
Ar
NHHet+
CuIII
X
Ar
CuIX
HetNH
Base
Base H+
Ar-XHetN-Ar
CuIII-X
HetN
Ar
Scheme 4: Catalytic cycles including Cu (III) intermediates
28
NN
NN
Ar
Ar X
Cu2O
Cs2CO
3, MeCN or DMF
H
+5mol%,
20 mol%105 or106
25-1100C, 24-90 hr
104 107
NN
N N
OH NOH
105 106
In the above reaction, if 105 and 106 are replaced with some of the ligands below, the
yield is improved.
108 80% 105 109 84% 105 110 96% 105 111 100% 105
112 96% 106 113 100% 106 114 53% 106
The above method was applied to arylation of ring-substituted pyroles 115; but
here, there was the formation of two possible arylated isomers 117 & 118.
I Br BrMeO
Me
Br
Br
EtO2C
BrNC N
29
NN
RR
R
X
NN
R R
R
Ph
NN
R R
R Ph
H
Cu2O
CsCO3
2 1
3
12
3
12
3
++5mol%
+
115 116 117 118
R1 R
2 R
3 X Solvent(temp.), time Yield (%) 3:4
CF3 H H I MeCN(82°C), 24hrs 100 -
CF3 H H Br MeCN(82°C), 96hrs 81 -
Me H H I MeCN(82°C), 24hrs 100 4:1
Me H H Br MeCN(82°C), 96hrs 68 3.2:1
Me H Me I MeCN(82°C), 96hrs 12 -
Me H Me I DMF(110°C), 24hrs 47 -
Table 4: Arylation of ring-substituted pyroles
Mulrooney35
, reported recent developments in copper-catalyzed N-arylation with
aryl halides, a reaction that was investigated by Venkataraman and co-workers.
30
NR
I
N
R
HR R
R
R
Cu complex
Toluene12
3 12
310-20mol%
110-1200C
+ 121
119 120 122
Cu complex: Cu (PPh3)3, R = H Cu(Phen)(PPh3)Br, R = Me Cu(neocup)(PPh3)Br
N N
RR CuPh
3P Br
121
The Cu(PPh3)3Br complex 121 was used as catalyst with CsCO3 as base in toluene
at 110-120°C for 24-32 hours. Various substituted arylamines and iodides underwent
reaction to form di- and triaryl substituted amines with yields from 25-88%.
R1 R
2 R
3 Ligand %Yield
H H H Cu(PPh3)3Br 75
H Ph H Cu(PPh3)3Br 70
P-CH3 H H Cu(PPh
3)3Br 88
H Ph H Cu(neocup)(PPh3)Br 78
H Ph O-CH3 Cu(neocup)(PPh
3)Br 88
Table 5: Reactions of arylamines with aryl iodides
31
In 2010, Joubert and co-workers36
, reported efforts devoted to the screening of a
large choice of metal catalyst (including Cu, Fe, Pd, Au, Rh, or Ru) for the coupling
between imidazole 123 and potassium trifluorophenylborate 124. They chose catalyst
(20%) loading as a standard with 40% of ligand if required. The reaction was carried out
at 40°C in open air at 0.08M of the catalyst. They found out that only copper led to
significant conversion in the desired product, no reaction occurred with any other metal
including iron.
N
N
BF3K
NN
Cupper catalystligand
H2O,H
400C, air,24hr[0.08]
+
123 124 125
Entry Catalyst Ligand Mol% Yield(%)
1 [Cu(OH)TMEDA]2 Cl
2 CH
2[COMe]
2 20 14
2 Cu(acac)2 CH
3COCH
2CO
2Et 20 8
3 CuCl CH3COCH
2CO
2Et 20 13
4 CuCl CH3COCH
2CO
2Et 20 27
5 CuCl CH3COCH
2CO
2Et 20 26
6 CuCl CH3COCH
2CO
2Et 10 12
7 CuCl CH3COCH
2CO
2Et 5 <1
32
8 CuCl CH3COCH
2CO
2Et 20 15
9 CuOAc CH3COCH
2CO
2Et 20 20
10 CuCl2 CH
3COCH
2CO
2Et 20 20
11 Cu(OTf)2 CH
3COCH
2CO
2Et 20 25
12 Cu(CH3COOHCO
2
Br)2
20 26
Table 6: N-arylation of imidazole: catalytic system optimization
Yu et al37
, reported a new set of reaction conditions optimized for the
copper(II)catalyzed N-arylation of primary and secondary amines, anilines 127 and
imidazoles with potassium aryltriolborates 126.
OB O
O
Cu(OAc)2
Me3NO
toluene
N
H
NH2127
(10mol%)
(1.1 equiv)
4A, MS, rt, 20hr
126 MS= Molecular seive 128 127
33
2.5 AIM OF THE PROJECT
The aim of this project is to synthesize new derivatives of angular
triazaphenoxazine ring system, which are: 11-phenyl amino-1, 8, 10-
triazabenzo[a]phenoxazin-5-one 11 and its 4-bromophenyl amino12, 3-chlorophenyl
amino 13 and 3-nitrophenyl amino 14 derivatives.
N
N O
N
NN
O
N
N O
N
NN
O
HHBr
11 12
N
N O
N
NN
O
N
N O
N
NN
O
O2N
HH
Cl
13 14
The syntheses will be done via copper catalyzed N-arylation of the 11-amino-1, 8,
10- triazabenzo[a]phenoxazine-5-one 10.
34
CHAPTER THREE
RESULT AND DISCUSSION
3.1 7-Chloro-5, 8-quinolinequinone 58
The synthesis of this compound was carried out in a five step reactions beginning
from the treatment of 8-hydroxyquinoline 46 with conc. hydrochloric acid followed by
the addition of sodium nitrite at a temperature of (0-4)0C for an hour. The mixture was
allowed to stand overnight at 0oC, washed and dried to give 8-hydroxy-5-
nitrosoquinolinehydrochloride 129, a bright yellow solid melting at 178oC (dec) (lit.
180oC (dec))
38
N
OH
N
OH
NO
H
Conc HCl, NaNO2
0-40C, 1hr
Cl-
+
46 129
The 8-hydroxy-5-nitrosoquinolinehydrochloride 129 was further treated with con.
nitric acid at 170C for 1hour 15min to release nitrogen(iv)oxide, made alkaline with cold
conc. potassium hydroxide and neutralized with acetic acid to obtain 8-hydroxy-5-
nitroquinoline, 130, which melting at 180oC (lit.181-183
0C )
38
N
OH
NO
H
N
OH
NO2
Conc HNO3, KOH, CH
3CO
2H
Cl-
+170C, 1hr15min
129 130
35
8-Hydroxy-5-nitroquinoline 130 was then converted to 7-chloro-8- hydroxy-5-
nitroquinoline 131 on treatment with 1M potassium hydroxide solution and sodium
hypochlorite at room temperature for about 1.5 hrs, after which the mixture was stirred
for further 2 hours, neutralized with acetic acid, washed with water, and filtered.
Compound 131 melted at 2380C (lit. 239-240.5
oC)
38
N
OH
NO2
N
OH
NO2
Cl
KOH, NaClO, CH3CO
2H
r.t, 3.5hr
130 131
The reduction of 7-chloro-8-hydroxy-5-nitroquinoline, 131 using potassium
hydroxide and sodium dithionite under nitrogen atmosphere, at a temperature between
50-80oC, produced 5-amino-7-chloro-8-hydroxyquinoline, 132, as a golden yellow solid,
melting at 1700C (lit. 172-173
0C )
38
N
OH
NO2
Cl N
OH
NH2
Cl
KOH, Na2S
2O
2
Nitrogen,50-800C
131 132
Finally, the 5-amino-7-chloro-8-hydroxyquinoline 132 was oxidized on treatment
with a mixture of 5M sulphuric acid and a solution of potassium dichromate at 0oC. The
precipitate was filtered washed with water and air dried to give 7-chloro-5, 8-
quinolinequinone, 59 a light tan solid melting at 174oC (dec) (lit.174 (dec.))
38
36
The compound 59 showed the following ultraviolet maximum absorption bands in
ethanol nm(logE), 208(2.078), 246(1.754), 440(1.993), 498(1.275), 658(1.171). The ultra
violet absorption maximum at 208nm was in agreement and within the range for
quinoline structure, while that at 440, 498 and 658nm are consistent with the colour.
N
OH
NH2
Cl N
O
O
Cl
H2SO
4, K
2Cr
2O
7
0 0C
6M (aq)
132 58
3.2 Potassiumphenyltriolborate 126
This compound 126 was synthesized using Yu X et al39
protocol by reacting
phenylboronic acid 133 with trimethylolethane 134 in a solution of potassium or lithium
hydroxide. The mixture was evaporated to dryness to get the potassiumphenyltriolborate
126, a white solid, melting between 278-280oC, and showed the following ultraviolet
maximum absorption bands in ethanol nm(logE), 218(2.611), 261(1.512).
B
OH
OHHO
HO
HO
KOH
OB
O
O
134
K+
-
133 126
Three other derivatives of potassiumphenyltriolborate 126 were synthesized from
3-chloro- 136, 4-bromo- 138 and 3-nitrophenylboronic acid 140.
37
The 3-chloro- 136 and 4-bromo derivatives 138 were synthesized from 3-chloro
135 and 4-bromophenyboronic acid 137 respectively and trimethylolethane 134 in a
solution of potassium hydroxide, while the 3-nitro derivative 140 was synthesized from
3-nitrophenylboronic acid 139 and trimethylolethane 134 in a solution of lithium
hydroxide. The 3-chloro- 136, 4-bromo- 138, and 3-nitro derivatives 140 all show similar
ultraviolet absorption bands as potassiumphenyltriolborate 126.
B
OH
OH
Cl
HO
HO
HO
KOH
Cl
OB
O
O
134
K+
-
135 136
B
OH
OH
Br HO
HO
HO
KOH
Br
OB
O
O
134
K+
-
137 138
B
OH
OH
O2N
HO
HO
HO
LiOH
NO2
OB
O
O
134
K+
-
139 140
38
3.3 11-Amino-1, 8, 10-triazabenzo[a]phenoxazin-5-one 10
Compound 10 was synthesized by the condensation reaction between 4, 5-diamino-
6-hydroxypyrimidine 60 and 7-chloro-5, 8-quinolinequinone 58 in the presence of
sodium acetate as base and benzene/DMF as solvent. The reaction occurred at a
temperature of 70-750C for 6 hours and the compound melted over 275-277
oC (lit.>300)
40
The ultraviolet maximum absorption bands in ethanol nm(logE), 207(2.697),
241(2.7), 351(2.282) 437(2.389), 498(1.064), are consistent with the assigned structure
of the phenoxazine ring and the colour of the compound, as seen in the absorptions
down field and in the visible region respectively .
From the infrared spectrum, the following assignments were made: 639, 741, 801,
831 and 882 cm-1
(C-H, out of plane indicating polynuclear aromatic compound), 1504cm-
1(secondary aromatic N-H), 1282cm
-1(C-O-C aromatic stretching) and 3248, 3453,
2926cm-1
(aromatic C-H stretch). These assignments are consistent with the assigned
structure.
The H1 NMR signals at d8.20(d, 2H, C2 and C4 protons), 7.90(d, 2H, C3 and C9
protons), 7.40(s, 1H, C6 proton), 3.4(s,b, 2H, Ar-NH2) and 2.5(s, DMSO) are consistent
with the assigned structure and the 13
C NMR signals around 173.71ppm(>C=O and C-
NH2), 140(>C=C< and >C=N) and 123.87-122.40(aromatic carbon) are also consistent
with the assigned structure.
39
N
N O
N
N
O
NH2
N
N
NH2
NH2
OH N
O
O
Cl
NaOAc(anhydrous)
benzene/DMF
12
3
4
678
9
10
5
11
70-750C, 6hrs
+
60 58 10
3.4 11-Phenylamino-1, 8, 10-triazabenzo[a]phenoxazin-5-one 11.
The synthesis of compound 11 involved the copper-catalyzed N-arylation of 11-
amino-1, 8, 10-triazabenzo[a]phenoxazin-5-one 10, with potassiumphenyltriolborate 126
catalyzed by Cu(OAc)2 in the presence of trimethylamine N-oxide, and 4Å molecular
sieve, using toluene/DMF as solvent at room temperature for 20 hours. The solid melted
at 218-220oC.
The ultraviolet maximum absorption bands nm(logE),206(2.156), 268(1.27),
360(1.117), 426(0.985), 500(0.651) agree with the structure of the phenoxazine ring and
the colour of the compound, as seen in the absorptions down field and in the visible
region respectively .
From the infrared spectrum, the following assignments were made: 674 and
753cm-1
(C-H, out of plane, indicating polynuclear aromatic compound), 1272 cm-1
(C-O-
C stretching, secondary aromatic amine) and 3439cm-1
(aromatic C-H stretch). These
assignments are consistent with the structure.
The H1 NMR signals at d8.40(d, 2H, C2 and C4 protons), 7.90(d, 2H, C3 and C9
protons), 8.0-7.80(m, 5H, protons of a monosubstituted benzene), 6.50(s, 1H, C6 proton),
3.40(s,b, 1H, >NH) and 2.50(s, DMSO) are consistent with the assigned structure and the
40
13C NMR signals around 173.71ppm(>C=O and C-NH2), 142.87(>C=C< and >C=N) and
131.40-127.53(aromatic carbon) are also consistent with the assigned structure.
N
N O
N
NNH
O
Cu(OAc)2, Me
3NO
toluene/DMFN
N O
N
NNH2
O
OB O
O
rt, 20hrs
K+
-
+ 4Ams
126 10 11
4Å ms = 4 Armstrong unit molecular sieve
3.5 11-(4-Bromophenylamino)-1, 8, 10-triazabenzo[a]phenoxazin-5-one 12
The synthesis of this compound 12 followed the same procedure as in the synthesis
of 11 above, but this time, the potassiumphenytriolborate 126 was replaced with
potassium-4-bromophenytriolborate 138. The solid 12 melted over 228-230oC.
The ultraviolet maximum absorption bands nm(logE), 219(2.536), 271(2.176),
360(1.512), 424(1.398), 500(0.921), are consistent with the assigned structure of the
phenoxazine ring and the colour of the compound, as seen in the absorptions down field
and in the visible region respectively.
The infrared spectrum showed peaks at 686, 752cm-1
(C-H, out of plane, indicating
polynuclear aromatic compound), 1273cm-1
(secondary aromatic amine, C-O-C aromatic
stretching), 1608cm-1
(C=O), 3438cm-1
(aromatic C-H stretch), which are consistent with
the assigned structure.
The H1 NMR signals at d8.20(d, 2H, C2 and C4 protons), 7.90(d, 2H, C3 and C9
protons) 7.30(s, 1H, C6 proton), 3.40(s, 1H, >NH) and 2.50(s, DMSO) are consistent with
the assigned structure and the 13
C NMR signal around 176.38ppm((>C=O and C-NH2),
41
142.87(>C=C< and >C=N) and 131.39-127.54(aromatic carbon) are also consistent with
the assigned structure.
N
N O
N
NNH
O
Cu(OAc)2, Me
3NO
toluene/DMFN
N O
N
NNH2
O
Br
OB O
O
Br
rt, 20hrs
K+
-
+ 4Ams
138 10 12
3.6 11-(3-Chlorophenylamino)-1, 8, 10-triazabenzo[a]phenoxazin-5-one 13
The synthesis of this compound 13 has the same procedure, reagent, and conditions
as that of compound 11, but in the synthesis of compound 13, the
potassiumphenyltriolborate 126 was substituted for potassium-3-chlorophenyltriolborate
136. The brown solid form was re-crystallized from ethanol and melted at 229-234oC
The ultraviolet maximum absorption bands nm(logE), 207(2.163), 211(1.933),
217(1.570), 274(1.093), 360(0.853), 499(0.575) are consistent with the assigned
structure of the phenoxazine ring and the colour of the compound, as seen in the
absorptions down field and in the visible region respectively.
The infrared spectrum showed peaks at 675cm-1
(C-H, out of plane, indicating
polynuclear aromatic compound), 1274cm-1
(secondary aromatic amine, C-O-C aromatic
stretching), 1648cm-1
(aromatic C=O), 3433cm-1
(aromatic C-H stretch), which are
consistent with the assigned structure.
The H1 NMR signals at d8.80(d, 2H, C2 and C4 protons), 7.90(d, 2H, C3 and C9
protons), 7.60(m, 4H, Ar-H), 3.50(s,b, 1H, >NH) and 2.50(s, DMSO) are consistent with
42
the assigned structure and the 13
C NMR signals around 140(>C=C< and >C=N) and 132-
128(aromatic carbon) are also consistent with the assigned structure.
N
N O
N
NNH
O
Cu(OAc)2, Me
3NO
toluene/DMFN
N O
N
NNH2
OCl
OB O
O
Clrt, 20hrs
K+
-
+ 4Ams
135 10 13
3.7 11-(3-Nitrophenylamino)-1, 8, 10-triazabenzo[a]phenoxazin-5-one 14
The synthesis of this compound 14 is also similar in procedure, reagents and
conditions with that of compound 11; the difference in the substitution of
potassiumphenyltriolborate 126 for lithium-3-phenyltriolborate 140. The solid was re-
crystallized from ethanol and melted over 229-242oC.
The ultraviolet maximum absorption bands in ethanol nm(logE), 207(2.027),
216(1.777), 245(1.640), 360(1.155), 420(0.865), 498(0.865), 659(0.700) are consistent
with the assigned structure of the phenoxazine ring and the colour of the compound, as
seen in the absorptions down field and in the visible region respectively.
The infrared spectrum showed peaks at 678, 748cm-1
(C-H, out of plane, indicating
polynuclear aromatic compound), 1273cm-1
(secondary aromatic amine, C-O-C aromatic
stretching), 1644cm-1
(aromatic C=O), 3462cm-1
(aromatic C-H stretch), which are
consistent with the assigned structure.
The H1 NMR signals at d8.40(d,b, 2H, C2 and C4 protons), 7.80(s,b, 2H, C3 and C9
protons), 3.50(s,b, 1H, >NH) and 2.50(s, DMSO) are consistent with the assigned
structure and the 13
C NMR signals around 140(>C=C< and >C=N) and 132-128(aromatic
carbon) are also consistent with the assigned structure.
43
N
N O
N
NNH
O
Cu(OAc)2, Me
3NO
toluene/DMFN
N O
N
NNH2
ONO
2
OB O
O
O2N
rt, 20hrs
K+
-
+ 4Ams
140 10 14
ELEMENTAL ANALYSIS
Compound
10
Calculated
(found)
(%)
11
Calculated
(found)
(%)
12
Calculated
(found)
(%)
13
Calculated
(found)
(%)
14
Calculated
(found)
(%)
Element
Carbon 58.87
(58.90)
66.86
(66.70)
54.29
(54.30)
60.72
(60.80)
59.07
Hydrogen 2.64
(2.59)
03.23
(3.31)
02.38
(2.29)
02.66
(2.59)
02.59
Nitrogen 26.42
(26.60)
20.53
(20.50)
16.67
(16.70)
18.64
(18.75)
21.76
Bromine
19.05
(19.00)
Chlorine
09.45
(9.50)
44
CHAPTER FOUR
EXPERIMENTALS
4.0 GENERAL
Melting points of synthesized compounds were determined using Scott scientific melting
point apparatus and are uncorrected. Ultraviolet and visible spectra were recorded on
Jenway 6405 UV/Vis spectrophotometer in the Departments of Pure and Industrial
Chemistry, University of Nigeria, Nsukka. Absorption maximum is given in nanometer
(nm) and (logE) in parenthesis. Infrared spectra data were obtained on FTIR-8400S in
NARICT, ZARIA and absorption were in wave number (cm-1
). Nuclear magnetic
resonance (1H-NMR and
13C-NMR) were determined on Variant 200MHz NMR machine
in Central Laboratory Obafemi Awolowo University Ile Ife and chemical shifts are
reported in the d-scale.
4.1 Synthesis of 7-chloro-5, 8-quinolinequinone 59
The synthesis of 58 is a five-step reaction, beginning with 8-hydroxyquinoline 46.
4.1.1 5-Nitroso-8-hydroxyquinoline hydrochloride 129
A solution of 8-hydroxyquinoline 46 (58g, 0.4 mole) and water (200 ml) was charged
into a liter beaker. Concentrated hydrochloric acid (75ml) and 200g of ice were added. A
solution of sodium nitrite (10g) in 100ml of water was added gradually with vigorous
stirring over 1hr at 0-4°C in an ice salt bath. The mixture was allowed to stand overnight
(about 14 hours) at 0°C, after which the product was collected by filtration and washed
with cold water. The product 5-nitroso-8-hydroxyquinoline hydrochloride 129 was air
45
dried; it gave a bright yellow solid (80g, 90%) and melted at 178oC (dec) (lit. 180
oC
(dec))38
4.1.2 5-Nitro-8-hydroxyquinoline 123
Finely grounded powdered 5-nitroso-8-hydroxyquinoline hydrochloride 129
(36.0g, 0.2mol) was added to a mixture of concentrated nitric acid (108 ml) and water
(72ml) at 17°C in a liter beaker. The mixture was stirred vigorously for over 1hour 15
minutes at 17°C in an ice bath, there was evolution of nitrogen(IV)oxide while the 5-
nitroso-8-hydroxyquinoline hydrochloride 129 was converted to the insoluble 5-nitro-8-
hydroxyquinoline nitrate. After the 1hour 15mins, with occasional stirring, the mixture
was diluted with equal volume of water. The mixture was cooled to 0°C and made
alkaline with cold concentrated potassium hydroxide solution (pH 13.0); the red
potassium salt was decomposed on neutralization with acetic acid and the product 5-
nitro-8-hydroxyquinoline 130 was filtered, washed with water, air dried and re-
crystallized from ethanol. It melted at 1800C (lit.181-183
0C)
38
4.1.3 7-Chloro-5-nitro-8-hydroxyquinoline 131
5-Nitro-8-hydroxyquinoline 130 (10.0g, 0.05mol) was suspended in liter of water.
One equivalent amount of 1M potassium hydroxide solution was added, the mixture was
stirred vigorously as sodium hypochlorite (72ml, 5%) was added in portions at room
temperature over a period of 1.5 hours. During the course of the addition, all the starting
materials dissolved and soon the orange salt of 7-chloro-5-nitro-8-hydroxyquinoline 131
begins to precipitate. After the addition of the hypochlorite, the mixture was stirred for
another 2 hours, neutralized with acetic acid, and stirred to permit complete conversion of
46
the precipitate to the free quinoline. It was filtered and washed with water; the solid
product was re-crystallized from aqueous ethyl acetate, to give 7-chloro-5-nitro-8-
hydroxyquinoline 131 (8.70g, 88%), which melted at 2380C (lit. 239-240.5
oC)
38
4.1.4 7-Chloro-5-amino-8-hydroxyquinoline 132
7-Chloro-5-nitro-8-hydroxyquinoline 131 (22.4g, 0.1mole) was grounded in a
mortar with 1M potassium hydroxide solution (110ml) to ensure complete reduction of
the insoluble potassium salt. The suspension was transferred to a liter three-necked round
bottom flask equipped with a long magnetic stirring bar with water (280 ml), the mixture
was heated in a water bath with vigorous stirring. 8M potassium hydroxide solution
(70ml) was added, while the heating continued and at 50°C, the mixture was treated with
sodium dithionite (70g). The mixture was re-heated to a temperature of 80°C and
maintained there for 10 mins, while a rapid stream of nitrogen gas was passed into the
flask. After 10 mins, more sodium dithionite (10g) was added, while the passage of
nitrogen gas continued for another 10 mins. The resulting suspension was cooled in ice,
under nitrogen gas and the precipitate was filtered, washed with cold water containing a
trace of dithionite and dried to give 7-chloro-5-amino-8-hydroxyquinoline 132 (22.3g,
99%), a golden yellow solid, which melted at 170oC (lit. 172-173
oC )
38
4.1.5 7-Chloro-5, 8-quinolinequinone 58
7-Chloro-5-amino-8-hydroxyquinoline 132 (22.3g 0.1 mole) was suspended in
water (60 ml) in a liter beaker equipped with a long magnetic stirring bar in an ice-salt
bath, 6M sulphuric acid was added to dissolve the amine 132; While vigorous stirring
continued, the solution was cooled down to 2°C and precipitated out in a finely divided
47
form. An ice-cold solution made up of 10% solution of potassium dichromate (103ml)
and 6M sulphuric acid (17ml) was then added all at once. The mixture was stirred and
cooled in the ice-salt bath for 15mins. The precipitated salt was filtered, washed with cold
water and air dried. A light tan solid was obtained, which on re-crystallization with DMF
and treatment with activated charcoal was precipitated out with cold water to give 7-
chloro-5,8-quinolinequinone 58 as a fine light tan solid (16.03g 72%),which melted at
174oC (dec) (lit.174 (dec.))
38
4.2 Synthesis of aryltriolborates
The procedure for the synthesis of the aryltriolborates was derived using the equation
of reaction derived by Yu et al39
B
OH
OHHO
HO
HO
KOH
OB
O
O
134
K+
-
133 126
4.2.1 Potassiumphenyltriolborate 126
Trimethylolethane 134 (5.0g) was dissolved in 1M potassium hydroxide solution
(10ml) at room temperature, the solution was stirred for about 20mins for complete
dissolution of the trimethylolethane 134. Phenylboronic acid 133 (5.0g) was then added,
and the mixture was further stirred for about 40minutes at the same temperature. The
product 126 was recovered by evaporation to dryness. The same procedure was followed
48
in the synthesis of lithiumphenyltriolborate, but here, 1M lithium hydroxide (10ml) was
used instead of potassium hydroxide.
4.2.2 Potassium 4-bromophenyltriolborate 138
The procedure for the synthesis of potassium 4-bromophenyltriolborate 138 was
the same as that of potassiumphenyltriolborate 126, but the phenylboronic acid 133 was
replaced with 4-bromophenylboromic acid 137.
4.2.3 Potassium 3-chlorophenyltriolborate 136
The procedure for the synthesis of potassium 3-chlorophenyltriolborate 136 was
the same as that of potassiumphenyltriolborate 126, but the phenylboronic 133 was
replaced with 3-chlorophenylboronic acid 135
4.2.4 Potassium 3-nitrophenyltriolborate 140.
The procedure for the synthesis of potassium 3-nitrophenyltriolborate 140 is the
same as that of Potassiumphenyltriolborate 126, but the phenylboronic acid 133 is
replaced with 3-nitrophenylboronic acid 139 and lithium hydroxide is used instead of
potassium hydroxide.
4.3 Synthesis of 11-amino-1, 8, 10-triazabenzo[a]phenoxazin-5-one 10
4,5-Diamino-6-hydroxypyrimidine 60 (0.65g, 0.05mole) suspended in benzene
(40ml) was added into a 100ml two-necked round bottomed flask equipped with reflux
condenser, thermometer and magnetic stirring bar in a water bath. Anhydrous sodium
acetate (1.0g, 0.12 mole) was added to the mixture, followed by addition of DMF (5ml)
49
to dissolve the compound 60. The mixture was heated on stirring for 45minutes at 70-
75°C, 7-chloro-5, 8-quinolinequinone 58 (0.8g, 0.04mole) was added to the mixture and
both stirring and heating continued. The mixture was refluxed with continuous stirring
for 6 hours at the same temperature 70-75°C; the reaction vessel was then chilled, and the
content filtered; the filtrate was allowed to evaporate and then worked up to leave a red
solid product which was collected and re-crystallized from acetone to give 11-amino-1, 8,
10-triazabenzo[a]phenoxazin-5-one 10, which melted over 275-277oC (lit.>300)
40
The ultraviolet maximum absorption bands in ethanol nm(logE), 207(2.697),
241(2.7), 351(2.282) 437(2.389), 498(1.064), are consistent with the assigned structure
of the phenoxazine ring and the colour of the compound, as seen in the absorptions
down field and in the visible region respectively .
From the infrared spectrum, the following assignments were made: 639, 741, 801,
831 and 882 cm-1
(C-H, out of plane indicating polynuclear aromatic compound), 1504cm-
1(secondary aromatic N-H), 1282cm
-1(C-O-C aromatic stretching) and 3248, 3453,
2926cm-1
(aromatic C-H stretch). These assignments are consistent with the assigned
structure.
The H1 NMR signals at d8.20(d, 2H, C2 and C4 protons), 7.90(d, 2H, C3 and C9
protons), 7.40 (s, 1H, C6 proton), 3.4 (s,b, 2H, Ar-NH2) and 2.5 (s, DMSO) are consistent
with the assigned structure and the 13
C NMR signals around 173.71ppm(>C=O and C-
NH2), 140(>C=C< and >C=N) and 123.87-122.40(aromatic carbon) are also consistent
with the assigned structure.
The elemental analysis shows; calculated (%): C, 58.58; H, 2.64; N, 26.42. found:
C, 58.90; H, 2.59; N, 26.60
50
4.4 11-(Phenylamino)-1, 8, 10-triazabenzo[a]phenoxazin-5-one 11
A mixture of potassiumphenyltriolborate 126 (2.07g), copper acetate (0.12g),
trimethylamine N-oxide (0.53g) and powdered 4Å molecular sieve (1.94g) in toluene
(30ml) and DMF (5ml) was stirred for 5 minutes at room temperature, 11-amino-1,8,10-
triazabenzo[a]phenoxazin-5-one 10 (0.6g) was then added. The mixture was stirred for
20hrs at room temperature. After the 20 hrs, the solvents were allowed to evaporate and
then the product is washed with ice, filtered, and dried. The residue, a brown powder 11
is re-crystallized using ethanol and it melted at 218-220oC.
The ultraviolet maximum absorption bands nm(logE), 206(2.156), 268(1.27),
360(1.117), 426(0.985), 500(0.651) agree with the structure of the phenoxazine ring and
the colour of the compound, as seen in the absorptions down field and in the visible
region respectively .
From the infrared spectrum, the following assignments were made: 674 and
753cm-1
(C-H, out of plane, indicating polynuclear aromatic compound), 1272 cm-1
(C-O-
C stretching, secondary aromatic amine) and 3439cm-1
(aromatic C-H stretch). These
assignments are consistent with the structure.
The H1 NMR signals at d8.40(d, 2H, C2 and C4 protons), 7.90(d, 2H, C3 and C9
protons), 8.0-7.80(m, 5H, protons of a monosubstituted benzene), 6.50(s, 1H, C6 proton),
3.40(s,b, 1H, NH) and 2.50(s, DMSO) are consistent with the assigned structure and the
13C NMR signals around 173.71ppm(>C=O and C-NH2), 142.87(>C=C< and >C=N) and
131.40-127.53(aromatic carbon) are also consistent with the assigned structure.
The elemental analysis shows; calculated (%): C, 66.86; H, 3.23; N, 20.53. found:
C, 66.70; H, 3.31; N, 20.50.
51
4.5 11-(4-Bromophenylamino)-1, 8, 10-triazabenzo[a]phenoxazin-5-one 12
The procedure is similar with that of 10 except that the potassium
phenyltriolborate 126 (2.07g) is replaced with potassium 4-bromophenyltriolborate 138
(2.85g). The solid 12 melted over 228-230oC.
The ultraviolet maximum absorption bands nm(logE), 219(2.536), 271(2.176), 360
(1.512), 424 (1.398), 500 (0.921), are consistent with the assigned structure of the
phenoxazine ring and the colour of the compound, as seen in the absorptions down field
and in the visible region respectively.
The infrared spectrum showed peaks at 686, 752cm-1
(C-H, out of plane, indicating
polynuclear aromatic compound), 1273cm-1
(secondary aromatic amine, C-O-C aromatic
stretching), 1608cm-1
(C=O), 3438cm-1
(aromatic C-H stretch), which are consistent with
the assigned structure.
The H1 NMR signals at d8.20 (d, 2H, C2 and C4 protons), 7.90 (d, 2H, C3 and C9
protons) 7.30 (s, 1H, C6 proton), 3.40 (s, 1H, >NH) and 2.50(s, DMSO) are consistent
with the assigned structure and the 13
C-NMR signal around 176.38ppm((>C=O and C-
NH2), 142.87(>C=C< and >C=N) and 131.39-127.54(aromatic carbon) are also consistent
with the assigned structure.
The elemental analysis shows; calculated (%): C, 54.29; H, 2.38; N, 16.67; Br,
19.05. found: C, 54.30; H, 2.29; N, 16.70; Br, 19.00.
52
4.6. 11-(3-Chlorophenylamino)-1, 8, 10-triazabenzo[a]phenoxazin-5-one 13
The procedure is similar with that of 10 except that the potassium phenyltriolborate
126 (2.07g) is replaced with potassium 3-chlorophenyltriolborate 136 (2.42g). The brown
solid form was re-crystallized from ethanol and melted at 229-230oC
The ultraviolet maximum absorption bands nm(logE), 207(2.163), 211(1.933),
217(1.570), 274(1.093), 360(0.853), 499(0.575) are consistent with the assigned
structure of the phenoxazine ring and the colour of the compound, as seen in the
absorptions down field and in the visible region respectively.
The infrared spectrum showed peaks at 675cm-1
(C-H, out of plane, indicating
polynuclear aromatic compound), 1274cm-1
(secondary aromatic amine, C-O-C aromatic
stretching), 1648cm-1
(aromatic C=O), 3433cm-1
(aromatic C-H stretch), which are
consistent with the assigned structure.
The H1 NMR signals at d8.80(d, 2H, C2 and C4 protons), 7.90(d, 2H, C3 and C9
protons), 7.60(m, 4H, Ar-H), 3.50(s,b, 1H, >NH) and 2.50(s, DMSO) are consistent with
the assigned structure and the 13
C NMR signals around 140(>C=C< and >C=N) and 132-
128(aromatic carbon) are also consistent with the assigned structure.
The elemental analysis shows; calculated (%): C, 60.72; H, 2.66; N, 18.64; Cl,
9.45. found: C, 60.80; H, 2.59; N, 18.75; Cl, 9.50.
4.7 11-(3-Nitrophenylamino)-1, 8, 10-triazabenzo[a]phenoxazin-5-one 14
The procedure is the same with that of 10, except that the potassium
phenyltriolborate 126 (2.07g) is replaced with lithium 3-nitrophenyltriolborate 140
(2.20g). The solid was re-crystallized from ethanol and melted over 239-241oC.
53
The ultraviolet maximum absorption bands in ethanol nm(logE), 207(2.027),
216(1.777), 245(1.640), 360(1.155), 420(0.865), 498(0.865), 659(0.700) are consistent
with the assigned structure of the phenoxazine ring and the colour of the compound, as
seen in the absorptions down field and in the visible region respectively.
The infrared spectrum showed peaks at 678, 748cm-1
(C-H, out of plane, indicating
polynuclear aromatic compound), 1273cm-1
(secondary aromatic amine, C-O-C aromatic
stretching), 1644cm-1
(aromatic C=O), 3462cm-1
(aromatic C-H stretch), which are
consistent with the assigned structure.
The H1 NMR signals at d8.40(d,b, 2H, C2 and C4 protons), 7.80(s,b, 2H, C3 and C9
protons), 3.50(s,b, 1H, >NH) and 2.50(s, DMSO) are consistent with the assigned
structure and the 13
C NMR signals around 140(>C=C< and >C=N) and 132-128(aromatic
carbon) are also consistent with the assigned structure.
The elemental analysis shows; calculated (%): C, 59.07; H, 2.59; N, 21.76.
54
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