supervisor: dr. u.c. okoro february 2012 · 2015. 9. 16. · jacob, alifa david pg/m.sc/08/49858...

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

23

OR

Ar BOR

OO N

HOO N

Ph

Cu(OAc)2, HEt

3

CH2Cl

2, O

2

+4Ams,

92(a-f) 93 94

OO N

Ph-NO2-P

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.


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.


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


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


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





(aromatic C=O), 3433cm-1

(aromatic C-H stretch), which are

consistent with the assigned structure.


protons), 7.60(m, 4H, Ar-H), 3.50(s,b, 1H, >NH) and 2.50(s, DMSO) are consistent with

42


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.


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 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


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.


protons), 7.40 (s, 1H, C6 proton), 3.4 (s,b, 2H, Ar-NH2) and 2.5 (s, DMSO) are consistent


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


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.


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.


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.






(C=O), 3438cm-1

(aromatic C-H stretch), which are consistent with


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


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


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


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









protons), 7.60(m, 4H, Ar-H), 3.50(s,b, 1H, >NH) and 2.50(s, DMSO) are consistent with


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


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 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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metal catalysed coupling reactions. International J. Chem. 19(3), 110.

58

NCl

O

O

58

OB

O

O K+

-

126

59

Cl

OB

O

O K+

-

136

Br

OB

O

O K+

-

138

60

NH2

N

N O

NN

O

10

N

N O

N

NN

O

H

11

61

N

N O

N

NN

O

HBr

12

N

N O

N

NN

O

H

Cl

13

62

N

N O

N

NN

O

O2N

H

14

IR

NH2

N

N O

NN

O

10

63

N

N O

N

NN

O

H

11

N

N O

N

NN

O

HBr

12

64

N

N O

N

NN

O

H

Cl

13

N

N O

N

NN

O

O2N

H

14

65

1H-NMR

NH2

N

N O

NN

O

10

N

N O

N

NN

O

H

11

66

N

N O

N

NN

O

HBr

12

N

N O

N

NN

O

H

Cl

13

67

N

N O

N

NN

O

O2N

H

14

13

C-NMR

NH2

N

N O

NN

O 10

68

N

N O

N

NN

O

H

11

N

N O

N

NN

O

HBr

12

69

N

N O

N

NN

O

H

Cl

13

N

N O

N

NN

O

O2N

H

14

supervisor: dr. u.c. okoro february 2012 · 2015. 9. 16. · jacob, alifa david pg/m.sc/08/49858...

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