University of Nigeria Research Publications

OKEKE, Stephen O.

Aut

hor

PG/M.Sc/Ph.D/83/1856

Title

Synthesis and Industrial Applications of a New Angular Azaphenothiazine

Facu

lty

Physical Sciences

Dep

artm

ent

Pure and Industrial Chemistry

Dat

e

February, 1986

Sign

atur

e

SYNTHESIS AND INDUSTRIAL APPLICATIONS OF A NEW ANGULAR

AZAPHENOTHIAZINE

DEPARTMENT OF PURE AND INDUSTRIAL CHEMlSTRY UNIVERSITY OF NIGERIA

NSUKKA

FEBRUARY, 13t.36 .

U N I V E R S I T Y OF NIGERIA, NSUKKA DEPAHTmNT OF PUKE AND INDUSTRIAL CI-lEMIS1!XY

RESEARCH PROJECT

CODE : CI-IKM 581

TITLE : SYNTHESIS AND'INDUSTRIAL APPLICATIONS OF A NEW ANGULAR AZAPHENOTHIAZLNE

STEPHEN IF'EDILT OKEKE

PS/M. S c / P h . ~/63/1856

as p a r t of the degree r e q u i r e m e n t f o r t h e

award cf Master of Science? d e q r e ~ . i n t h e

Departirlent o f IPurti and Lnt fus t .~ . i ; l l C h c m i s t x y ,

F a c u l t y of P h y s i c a l Sc iences , U n i v e v s i t y of

N i g e r i a , N s u k k a .

SUPERVISOR: PROF. C. 0. OIOZFOR HEAD, DEPARTNSNT OF PURE AND I N D U S T R I A L CHEMISTRY.

DEDICATION

D e d i c a t e d t o my Father - 9 - *

Mr. E l i a s Okeke and t o the

m e m o r y of m y L a t e m o t h e r - - -. . .. . -

Mrs. F a i t h Okeke.

CONTENTS

2 . I I ISTORICAL ASPECTS -

2.1 Dyes and Plgment s -

2 . 2 Angular P h c n o t h i a z i n e s -

7 2. RESULTS AND D I S C U S S I O N -

PAGE -

ii

ACKNOWLEDGEMENT

W e v e r y o f t e n a c h i e v e o u r g o a l s and o b j e c t i v e s t h r o u g h shaiying,

dependence and a s s i s t a n c e o f o u r f e l l o w human b e i n g s . I t w i l l t h e r e f o r e

be u t t e r d e c e i t t o c l a i m t h i i t a w o r k such as t h i s . h a s erncrtjed e n t i r e l y

f r o m p e r s o n a l . a n d u n a i d e d e f o r t s . I t i n e v i t a b l y i n v o l v e d t e c h n i c a l i t i e s

r e q u i r i n g c o n s u l t a t i o ~ i a n d d e f i n i t e d i r e c t i v e s f rom e x p e r t s . I t h e r e f o r e

c a n n o t e v e r a d e q u a t e l y acknowledge t h e d e p t h o f g r a t i t u d e I o w e s e v e r a l

p e o p l e , f r i e n d s a n d a c q u a i n t a n c e s who, t h r o u g h t h e i r d i s c u s s i o n s w i t h m e

o r t h e i r r e c o n m e n d a t i o n s of u s e f u l s o u r c e s o f i n f o r m a t i o n , have o f f e r e d

m e e n c o u r a g e m e n t , a s s i s t a n c e and g u i d a n c e s i n c e I s t a r t e d on t h i s s t u d y .

My s i n c e r e s t g r a t i t u d e g o e s f i r s t t o my S u p e r v i s o r P r o f . C . O . Okafor

who, h i s p o s i t i o n as the Hcad o f Depar tment not .wi ths t .anding , r e l e n t l c s s l y

d i r e c t e d and s u p p o r t e d me t o makc t h i s work an e x i s t i n g r e a l i t y . I am

h i g h l y i n d e b t e d t o my p r o f e s s o r s and l e c t u r e r s i n t h e Depar tment o f P u r e

a n d I n d u s t r i a l C h e m i s t r y who put i n t h c i r bcst l n the p~:occ,ss of my

Eorm;iti.on to t.1) i s st ,1qc1 of rilv . ~ ~ J I ~ c ~ I I I ~ ( . : ; t < ~ ( 1 1 : ; .

My w a r m r e g a r d s i ind sincer: i.ir<.\nk:; i-.o r i r . C . N . O h i j loror a n d

D r . P.A. Akah a l l o f Pharmacognosy and T o x i c o l o g y Depar tment f o r t h e i r

i n v a l u a b l e a s s i s t a n c e i n t o x i c i t y t e s t c a r r i e d o u t on my compound.

My r e g a r d s w i l l b c incoi!iplete i f p e o p l e like Messrs Obi OkeruLu

Uche Okoro , Augus tus Uzoukwu, P e t e r Awachie, M.C. I d i g o , M i s s I h e s i n a c h i

Eluwa and o t h e r inembers o f t h e P o s t - g r a d u a t e L a b o r a t o r y o f t h e d e p a r t m e n t

who I h a v e n o t n ~ e n t i o n c d .

iii.

T e c h n i c a l s t a f f such a s P t r . F. I . Ozoh o f t h e Pos t -g radua te Labora to ry

and YE. F.U. Ekezie of t h e glass blowing worksnop s h o u l d a l s o have a

share o f my g r a t i t u d e .

M y u n r e s e r v e d t h a n k s and regards a l s o go to some persorial Ericr-lds,

J o y Ezenlba, J a n e Nwank~wor and Uzoanlaka Nwajagn for their t i e l p either

by b r i n y i n g food to me while in t h e laboratory or i n any cirh::t- for!:?

which l s d to t h e s u c c e s s f u i c o m ~ l e t i o n of th is or!;.

Fina1.l~ my g r e a t e s t gratitude 9oes to my parfent:;, xy yoi inq?r

brother M r . C h r i s Okeke and e l d e r byrother Nr. Emma. ~ k e k t ? ',;rhose

u n t i r i n g e f f o r t s and ps t i cncc? sustained i l l 2 t tiroughout Iny pcriod cf

study i n t h i s U n i v e r s i t y especial.ly i n e n s u r i n g that they attend to

ny unending demand f o r f i n a n c i a l assistance. Nay God guide and

p r o t e c t svery o n e of you.

Z-A1nino-3-111~.rc,1pto-6-pico1ine obtained by hydrolysis of 2-dmino-3-

n~aclc by el cmcni '11 analys i s , ir , uv and nrrir spectroscopy . Soli~t. ~ I I ( : I I I i c .< i 1

f u l l y . 'I'l~csc~ react loris . ,.. l.ude reduction with s o c l i u u i i i i l liionlta (Na 0 ) 2%') /I

eva lua t ion t-ests- It proved to possess ex t remely good f a s t n e s s to

l i g h t , water, alkaline and i r o n i n g . Varn i shes and shoe polish were

prepared using conpound 1 as the d y e s t u f f . The t o x i c i t y of t h i s new

r i n y compound was also s t u d i e d and the measured LDsO (39.81 mg/kg) of

10-methyl-6-chloro- 1 I-am-5fI-benzo [a] ~~~~~~~~~~~~~~one - 1 i s w i t h i n the

acceptable limits for dyes.

1. INTRODUCTION

Dyes and pigments have occupied an i n p o r t a n t place i n h u t e r o c y u 1 . i ~

chemistry. Some hetcrocyclic compounds are marketed for dyelnq t e x t i l e s

and others f o r other purposes. Such h e t e r o c y c l i c compounds i nc lude t h e

a z i n e dyes. This cldss i n c l u d e s t h e d e r i v a t i v e s of the heterocyclic

compounds, phenazinc ( 2 ) - , p h c n o t h i a z i n e (31 - and phenoxaz ine ( 4 ) - .

The i n d u l i n e s arc d a r k - b l u e phcnazine de r iva t ives produced b y

1 h e a t i n g mixture of p-arninoazo benzene, a n i l i n e , and a n i l i n e h y d r o c h l o r i d e .

The simplest i n t e rmed ia t e which can be isolated from the r e a c t i o n mixture

is Indamine Blue ( 5 1 , which undcrgocs f u r t h ~ > r r f a c t i o n s t o give -

The i n d u l i n ~ s a re s o l u b l e i n oils a n d in a l c o h o l s and are u s e d for

colouring l a c q u e r s , polishes etc. On s u l p h o n a t i o n t h e y are converted i n t o

1 water-soluble p r o d u c t s which arp u s e d as dyes and i n making inks .

1

M ~ ~ t . h y l ~ ~ n ~ ~ h l ur\ ( 7 ) .-- ' w i t h phcnothiazine r i n g s t r u c t u r e was obl air1c.d

of c:hloranil j n the presence of a n ac id -b ind ing a g e n t . Ring-clusurc~

w a s achievc?d by h e a t i n g i.n n i t r o b e n z e n e i.n t h e prescncc of p h o s p l l o r u s

p t : r i ( . I s , t ~lur-ides. : : ~ ~ L p h o n ; l t i rig ,the result i n ~ j di-0xd~i11t: gilvv LIIc! w ~ l r . 1 .

I I I I r c t ( f j ) (Schilmc I ) . .-

l 'helre ~lrr . of c o u r s e otlicr flJl I I IS o f h e t e r o c y c 1 . i ~ clycr-;, i~ lwy i t~ullldr,

3 I ,3 t i i i azo le , c : y , ~ ~ t i n e and a c r i d i n e dyes . For ! IIL! pr1rpo:ic of t l i ~ :; ~s 1~ k ,

WP s h ; ~ 11 curiccrll oi iielves w i t - h a z i n e dyes in . !cncral 41ld ~dic.noL11 i ,LZ i r i p

and i t s a z ~ - , ~ n ; l l o g u e s i n p a r t i c u l a r . Men t ion s h o u l d I,e made of uthl;r

1 I I I I ~ I I n i I s r v v I I I i t . I : .

.I dye.

Tlri:r~a 1 1 ~ s I ~ ~ ~ ~ - n a n increas t -d intcrc:.!. o n L i l t s y n l i ~ c , s j . r ; ~ I I I I I ~ I ~ I L I ~ i L:A L . l o l l : ;

4 of phcllotkiaz i n1.s , a z a p h e n o t h i a z i n e s and t l i c ~ i r cler i vaLi vc25.

Scheme 1.

Such i n t e r e s t i s s t i m u l a t e d by t h e i r wide i n d u s t r i a l and pharmacoZogica1

a p p l i c a t i o n s . It i s n o t therefore s u r p r i s i n g t o observe t h a t i nc reased

r e sea rch i - n t e r e s t is shown n o t on ly on t h e chemistry of phenothiazine and

recur so r s . azaphenothiazine but a l s o on t h e i r pL

Az.aphr1no t h i a z i n e compounds are the ana logues of phenothiazinc . i n a d d i t i o n a l 5

wilich/;lnnular n i t r o g e n atom/atorns form n a r t of' t h e r i n g s t n l c t u r e .

'!YE n i troqi\n atom or atoms c o u l d be l o c a t e d i n r i n g R or i l l rin!js A a ~ ~ t l

C a s t h e casc m a y be. ( S t r u c t u r e s 9 and 1 0 ) .

A s orw o t Llic m o s t u s e f u l h e t e r o c y c l i c r i n g s so f a r knovm, ~ . x l c n s i v c

s t r u c t u r a l m o d i f i c a t i o n of p h e n o t h i a 2 i n e an3 i ts d e r i v a t i v e s a r e still

i n progress i n a n a t t e m p t to improve t h e i r b i o l o g i c a l a c t i v i t i e s and to

4 5 reduce thc! u n d e s i r a b l e side e f f e c t s . Okafn r i n h i s review uf s t u d i c ~ s

i n t he heterocyclic s e r i e s highlighted t h e c h e m i s t r y and t h e a p p l i c a t i o r l s

o f n i n e monoam- and f o u r d i a z a p h e n o t h i a z i n e s . There is . l b s u r c c c r ~ t

report4 on t h e importance of 1 ' s e aza- and th ia -ana logues . Thc m s t

6 , ,7 u s e f u l compounds i n t h e s e s e r i e s are t h e dur ~ v a t i v e s uE 1 - a m pt~c~not I1 rc1 L I l lc,:,

8 9 fo l lowed by 1,2-tiiaza-, 2,3-diazcl-, and t l i u n 2,4-diazaphenothiazincu .

In most new a z a p h e n o t h i a z i n e s , there is t h e r e f ore re t e n t lurl o f r l n g

n i t r o g e n i r ~ C-1, C-2 and C-3, C-l and C - 3 , C-3 a n 1 1 C-4 or n v%irlc7t iv11 U I

them r e s u l t i n g I n d i a z a - , LL iaza- a n d t e t r a z a p h e n o t h i a z i r ~ e s a s t h e case

S y n t h e s i s of the d e r i v a t i v e s of a n g u l a r phenothiazirici r i n g s y a - + cm

i l I ) 1. r ~ ~ p o r t ~ r l by Bernthsen1° i n 7D'i9

1 1 - S i n c e t l w n , t h e y are used immensely i n t h e dye i n d u s t r y w h e r e t l i e y

constitut c the rria j u r class of su lphur dyes. The synthesis of image-for ~ ~ ~ i n g

11 rcpurt~d Ly Lony and coworkers . These dyes arc u s e d t r t ~ ~ ~ ~ c n d c ~ u : ; l y 1 1 1

pho togrdph i.c i n d u s t r y . S i n u c t h e observed p r o p e r t i e s o f l i n e a r phenc ) th i ; l z ine r-irlc~ :;y:iLc;,:

-1 are g e n e r a l l y enhanced by i n c o r p o r a t i n g one or more d n n u l a r nillogen

a torn/atoms i n t o t h e r i n g , w e theref ore embarked on thc syn t l l e s i s ariil

i n d u s l r i a l applications of a new angular p h c n o t h i a z i r l e r in(^ sy:.L(>r~l h i LII

o n e a n n u Lar n i t r o g e n a tom.

2 . HI!?TORICAL ASPECTS

2 . 1 Dyes and Pigments

1 The use of n a t u r a l dyes f o r c o l o u r i n g f a b r i c s and m a t e r i a l g e n e r a l l y

goes Sack t o a n t i q u i t y . Some o f t h e most i m p o r t a n t of these were m a d d e r ( l 2 1 , -

i n d i g o (13) - and t y r i a n purple ( - 14) .

The f i r s t i m p o r t a n t development i n dye ing w i t h n a t u r a l dyes can be said

to have been t h e d i s c o v e r y o f the process of mordanting. T h i s p r o c e s s

enables d i f f e r e n t shades o f c o l o u r t o be o b t a i n e d from t h e dye by f i r s t

t r e a t i n g t h e m a t e r i a l t o be dyed w i t h a mordant ( i . e a metallic e lement

t h a t can a c t a s an a c c e p t o r t o an electron donor t o form a c o - o r d i n a t e

bond e.g aluminium, t i n , iron and chromium). The discovery of logwood

w a s also made and t h i s i s a n e x t r a c t o b t a i n e d from t he heartwood o f t h e

1 tree Haematoxylon Campechianum , c u l t i v a t e d i n C e n t r a l America and t h e

West I n d i e s . It i s h i g h l y used I n t e x t i l e and l e a t h e r d y e i n g . Most of

t h e dyes i n use today a r e , however, of synthetic o r i g i n . T h i s i s because

mos t of the plants th rough which these n a t u r a l dyes are o b t a i n e d are no

7.

more a v a i l a b l e i n t h e i n d u s t r i a l i s e d count r i -es .

3 The f i r s t s y n t h e t i c dye, mauvein (15) w a s d i scovered by P e r k i r ~ i n -

1856, i n t h e course of an a t tempt t o make qu in ine .

Mauvein (15) was made by o x i d i s i n g a n i l i n e su lpha t e with dichromate s o l u t i o n . -

The p e r i o d , 1856-1870 saw t h e d i scovery of severa l important dyes

inc luding magenta (16) - (i .c t h e f i r s t t r iphenylmethane b a s i c dye) j ,

ethylv violet ( 1 7 ) -- rrhirh was produced i n 1061 by Lauthl and the f i r s t

8.

3 s u c c e s s f u l a z o dye Bismarck brown (18) - was s y n t h e s i z e d by M a r t i n s and

Caro. Between 1870 and 1655, a g r e a t e r number of dyes w e r e s t i - l l

d i s c o v e r e d , among which may be mentioned Methylene Blue ( 7 ) 2 , T a r t r a z i n e - 1

(19) - produced by Z i e g l e r l i n 1084, Congo Red ( 2 0 ) - s y n t h e s i z e d by B o t t i g e r

12 Ber thsen i n IS03 ciiscovered p h e n o t h i a z i n c , the p a r e n t conlpound of

i ~ ~ e t h y l c n e b l u e , a c c i d e n t a l l y w11cn hc was c a r r y i n g o u t c l a s s i c a l s t u d i e s

on t h e s t r u c t u r e of t h e t h i a z i n e dyes .

2 . 1 . 1 Chemical C l a s s i f i u a t i o n o f Dyvs

Dyes may be classified a c c o r d i n g to t h e l r chemica l c o n s t i t u t i o n and

a c c o r d i n g t o t h e i r method of a p p l i c a t i o n . The former a c t h o d can be

3 13 subd iv ided I n t o t h e f o l l o w i n g : (i) azo dycs ; (li} i n d i g o i d dycs ;

1 13 (iii) an thraqu inone dyesI3; ( i v ) s o l p h u r dyes ; ( v ) t r i p h e n y l m e t h a n e dyes ;

1 15 ( v i ) meta l p h t h a l o c y a n i n e s ; ( v i i ) h e t e r o c y c l i c dyes -

9 .

(i) Azo dyes

These are i n s o l u b l e pigments made by c o n v e r t i n g an a r o m a t i c p r imary

ami.ne into i t s diazoniurn s a l t ( i .e a p r o c e s s known a s d i a z o t i s a t i o n j and

c o u p l i n g t h e l a t t e r w i t h a pheno l i n a l k a l i n e s o l u t i o n o r wi th a n amine

i n a c i d s o l u t i o n .

Phenols and amines o f t h e benzene s e r i e s coup le w i t h diazonium s a l t s

1 , 3 i n the para p o s i t i o n t o give azo compounds . When t h e p a r a p o s i t i o n i s

occup ied by a group o t h e r t h a n hydrogen c o u p l i n g takes place i n t.he o r t h o

p o s i t i o n . I f o r t h o and p a r a p o s i t i o n s a r e a l l occup ied c o u p l i n g d o e s

n o t t a k e p l a c e .

OH

+ N a O H A r N = NCL- + p A ~ N = N ~ ~ Nd

3 An example of an a z o dye is Bisniarck Brown 118) - . I t is t h e f i r s t

s u c c e s s f u l b a s i c a z o dye s y n t h e s i z e d by Mar t ins and Caro.

(ii) I n d i g o i d dyes

I n d i g o ( 1 3 ) l 3 is one of the most a n c i e n t u i dyes a n d still on? of t h e -

most impor tan t b l u e dyes. T t i s used f o r dyeing and p r r n t l n g cotton,

b u t it i s d l s o uscri for dyeing wool.

Formerly i n d i g o was o b t a m e d f rani p l a n t s of t he genus ---- Indlgoferc l ,

whrch c o n t a i n s t h e g l u c o s i d c known a s ~ n d i c ~ n . Under t h e m f l u c n c e o f

a c l d s o r enzymes, i n d i c a n (21) - is hydro lysed t o g l u c o s e and i n d o x y l .

\

The indoxyl i 2 2 - ) on aerial o x i d a t i o n g i v e s i n d i g o ( - 13) . (Scheme 2 ) .

Scheme 2:

Ind igo used i n dye ing today i s s y n t h e s i z e d because o f t h e ease o f

fo rmat ion by s y n t h e s i s from a n i l i n e and because of s c a r c i t y o f I n d i g o f e r a

P l a n t s i n many i n d u s t r i a l i z e d c o u n t r i e s . Ind igo is i n s o l u b l e I n wa te r and

m u s t f i r s t be c o n v e r t e d i n t o a s o l u b l ~ form b e f o r e it can be u s c d for

dye ing . T h i s i s achieved by a g i t a t i n g IL w l t l ! a n a l k a l i n e s o l u t i o n oE

sodium d i t h i o n i t c , when t h e s o l u b l e sodium s a l t of i n d i g o ( t h e reduced

form) is formed ( 2 3 ) . -

The material t o be dyed is t h e n soaked in t h e a l k a l i n e s o l u t i o n , t h e

e x c e s s l i q u o r i s squeezed o u t , and on exposure t o a i r o r on t r e a t m e n t

with an o x i d i s i n g agent t h e i n s o l u b l e form of t-he dye is r e g e n e r a t e d

i n and on t h e fibrr.

(iii) Anthraquinone Dyes

The f irst an th raqu inone dye was a l i z a r i n ( 2 4 ) which was f o r m e r l y -

u s e d as a mordant dye f o r c o t t o n , and i s nowadays c h i e f l y used i n t h e

manufacture o f p igments . It i s now made s y n t h e t i c a l l y and it d y e s wool

1 a b l u i s h r e d on an aluminium mordant .

1 3 A l i z a r i n (24) c r y s t - a l l i z e s a s dark r e d p r i s m s w I A i ~ ~ ( : h m ~ l t c r t -

28g0 to 290°. I t i s i n s o l u b l e i n xater but d i s s o l v e s i n sodium h y d r o x i d e ,

g i v i n g a v i o l e t s o l u t i o n of sodium a l i z a r a t e ( 2 5 ) . I t i s a l so known as - a poLygenetic nurdixr t dye because it develops a v a r i e t y of colours on

d i f f e r e n t mordants . A s exampl.es, i t g i v e s a r e d c o l o u r w i t h aluminium

w i t h tin mordant. mordant and a p i n k colour

( i v ) Su lphur Dycs

These a r e c o m ~ l e x s u 1

l p h u r - c o n t a i n i n g dyes , most o f which a r e i n s o l u h

i n w a t e r . L i k e t h e i n d i g o i d dyes they must first be c o n v e r t e d i n t o a

s o l u b l e form, which i s achieved by reducing w i t h sodium d i t h i o n i t e l ' o r

sodium sulphide. The m a t e r i a l t o be dyed i s t h e n soaked i n t h e s o l u t i o n o f

t h i s r educed f o r m , t h e excess s o l u t l o n is pressed o u t , and on e x p o s i n g

t h e m a t e r i a l t o a i r , t h e s o l u b l e form of t h e dye i s o x ~ d i s c d back t o t h e

i n s o l u b l e fo1wi.n and on t h e f i b r e . S u l p h u r d y e s arc f a s t t o wash ing .

They are u s e d f o r d y e i n g c o t t o n , and s y n t h e t i c f i b r e s s u c h as n y l o n .

They are n o t u s e d f o r d y e i n g p r o t e i n f i b r e s b e c a u s e t h e a l k a l i i n t h e

s u l p h i d e d y e b a t h would damage t h e s e p r o t e i n f i b r e s . An example of a

I s u l p h u r d y e i s Hydron B lue R ( 2 6 ) . -

(v) T r i p h e n y l n e t h a n c byes

13 T r i p h e n y l m e t h a n e d y e s a r e d c r l v a t i v c s of t r i p h e n y l m e t h y l c a t i o n .

They are b a s i c d y e s f o r wool o r s i l k o r s u i t a b l e inordanted c o t c o n .

M a l a c h i t e g r e e n (20) i s a t y p i c a l example t h a t .is p r e p a r e d by concki-15rj n q -

b e n z a l d e h y d e w i t h d i n l e t h y i a n i i i n e and oxiti.izi.ng t h e i t - i t e rn i cd ia t c L ~ u c o

b a s e 2 7 . -

( v i i) Heterocyclic Dyes -- 1Ic . l e r ocycl ic dyes are coloured c y c l i c compo~inds w i t 11 t hc r- i rig

co11t , l i l l j ny carbon and o t h e r elements, t h e commonc!st bc 111cj o:,ycjc,n,

r ~ i L-r c q . 1 1 sulphur. Soliic (ire used fo r d y e i n g LcxL i Lti:;, < . i ~ i i I ot l ~ i > r :;

for c > t 1 1 ~ ; ~ . purposes. Exaniples of such dyes arc SOIIIC L ~ c t i v i \ I L I I v ( j ~ 1 1 -

15 c o l l t ,.I i.11 i r ~ c j ~.t.mpounds used as both d y e s a n d pigmcrlt:; . 'l'11c C : " I I ! [ ) O ~ I I I ( ~

3 1 W L I : ; pi oparc:d i n 9 7 . 4 % y i e l d by t r e a t i n g 30 w i t 1 1 ,.~dipo\iL t l i l o c i ( l c . i 11 -- -

sub; t L 1 LI 1 ctl urlinc 3 2 was s i m i l a r l y prepared. -

t HN d.%,

I

Sunw h s i c oxazine dyes 15

pol -yes tc r f i b r e s and f a s t b lue

dye ( 3 4 ) - w ~ t h phenoxazine ring

s u i t a b l e for dyeing a c r y l l c E I I I ~ C ~ C . I ( I - I I I O ~ I t ~(bd

shades w e r e r e p o r t e d . Tr ip l -~cnol~ i.soxaz i .11~

L b system was prepared by c y c l ~ z a t ic of - 3 2 .

17 3,7-Bis (diakylamino) - 10-haloacetyl phenoxazine d e r i v a t i v e s forming

deep b l u e c o l o u r s on c o n t a c t with a c i d i c m a t e r i a l s , were prepared and used

a s co lou r formers i n copying paper . For example 3,7-bis(diethy1amino)

phenoxazine ( 3 5 ) - i n t o luene was t r e a t e d with c h l o r o a c e t y l c h l o r i d e t o

g i v e compound 36.

Synthesi-s of compounds with high dyeing potent . ia1 which have angular

phenoth iaz ine and angular phenoxazine r i n g systems have been r e p o r t e d .

Some d i f f u s i b l e imacje-forming dyes 37 and 33 con ta in ing amino and imino - -.

11 groups r e s p e c t i v e l y w e r e r e p o r t e d by Long -

i r ~ photoc~ r,lpfl ic i~ ldu : i try was also reported.

' J ' f l iazinc. dyes ~ ~ s e f u l as magenta photographic d y e s are ~uccnufdc tured h y

reaction of substituted n a p h t h o q u i n o n e wi th t h iourt.<r i 11 c j l nc. i , i l , I ( ( . I I ( .

0 0 I I I 0 - 0 for 2-6 h o u r s , hydrol-ysing t11e r~!s~tl l arlL L,r o c l u c s ~ , c ~ l c i

coupl~ng w i t h substituted P-phenylenediamine i n t h e presence of an

acid acceptor. (Scheme 3) .

Scheme 3: --

Photograpllic dyes acting as light.-sensitive c o p y i ~ l g ~ r i d l ~ c r - i a l W L I : , , - ~ l s o

19 reporLet1 by Gcvaert-Agfa . '?'hey are capolymcrs of benzo-phenothiazine

a n d e t - l~yl hyd r r~xyc thy lce l lu lo se and when coa t ed on to a g l a s s p la t (> dnti

i ~ r a d i ~ i t e d undcr a nuga t lve , they give va r ious c o l o u r s of p o s i t i v e images.

A c h e i r ~ o t h r r ~ ~ p e u t i c dye which 1 s used as tumor growtll r e t a r d a n t as w ~ f l l CIS

2O,2l,23 d i f f e r cwt i . l l t i s s u c - s t a i n i n g dve was r epo r t ed by Crossley and

co-workers. A n example of such a dye i s 5-ben~ylamino-9- ( d i b u t y l a m i n o ) -

411-bpnzo la j phcnoxazine (4 3 ) . Crossley and coworkers 21,24

- a l s o l r i v t ? ~ t j i j ' ! t v d

the dyr inq potency and the drug a c t i v i t y o f compound - 44 with a h e t e r o c y c l i c -

amlrlo group at 5 - p o s i t ~ o n .

5-~thyl~(2-pyridyl)-arnino-9-dibutylamino benzo[alphenoxazine ( 4 4 ) did n o t -

s l i o w s i g n i f i c a n t a c t i v i t y as tumor growth- re ta rdant , howcvcr L l ~ c : c i y r ~ i n c ~

potcncy w a s ve ry encouraging.

2 2 A nurher of po lynuc lear h e t e r o c y c l i c c n m p o u r d s 11, I a s disperse tlyt:s

18.

have been successful . ly synthes ized . They are used for dyeing pu lyes tk r

f i b r e s g iv ing the l a t t e r a grey shade. They have good r e s i s t a n c e t o

0 l i g h t , washing a t 40 , co ld water , a l k a l i n e and a c i d p e r s p i r a t i o n , and

dry rubbing. Such a polynuclear compound, 4 7 , a s an example i s prepared -

by c y c l i z a t i o n of naphthacridan ( 4 5 ) with a n t h r a n i l i c a c i d ( 4 6 ) - and

a c e t i c anhydride i n presence of anhydrous z inc c h l o r i d e f o r I f hours a t

0 100-115 r e su lk ing t o compound 4 7 . -

2 . 1 . 2 C l a s s i f i c a t i o n of Dyes Bascd on t h e i r Method of Appl ica t ion

In t h e c l a s s i f i c a t i o n of dyes according t o t h e i r method of a p p l i c a t i o n ,

cons ide ra t ion i s qiven t o thc na tu re of the dye a s wel l as t h e f i b r e t o

be dyed. T e x t i l e fibres can be d iv ided from the p o i n t of view of dyeing

i n t o : ( a ) p r o t e i n f i b r e s , inc luding wool, n a t u r a l s i l k and h a i r ;

(b ) C e l l u l o s i c f i b r e s , t h e most important o f which are c o t t o n and v iscose

rayon; ( c ) a c e t a t e rayon and c e l l u i o s e t r i a c e t a t e f i b r e ; (d) s y n t h e t i c

f i b r e s . A genera l account of t he a p p l i c a t i o n of the va r ious c l a s s e s of

dyes t o t hese f i b r e s i s given a s fo l lows:

(i) Acid Dyes

1 3 These are t h e most important dyes f o r p r o t e i n f i b r e s , and are found

a s t h e sodium s a l t s of carboxyl ic o r sulphonic a c i d s . An example of an

a c i d dye i s sodium a l i c a r a t e ( 2 5 ) which is formed by d i s s o l v i n g

13 a l i z a r i n ( 2 4 ) i n sodium hydroxide s ~ l u t i o n . A l l a c i d dyes a r e water -

so lub le and so-ca l led because of their a p p l i c a t i o n to the f i b r e from

aqueous s o l u t i o n conta in ing su lphur i c a c i d , acetic acid or the ammonium

s a l t s of t hese a c i d s . The process of dyeing p r o t e i n f i b r e s with acid

dyes involves s a l t formation Setwcen t h e nega t ive ions of t h e dye and t h e

f r e e amino groups of t he f i b r e .

Acid dyes may h e subdivided i n a very general manner according t o t h e

proper ty of t h e ind iv idua l dye t o promote c o l o r a t i o n of tile p r o t e i n

f i b r e from a pu re ly aqueous solution. Dyes tha t posses s l i t t l e o r no dyeing

1 proper ty undelr these cond i t i ons a r c usua l ly app l i ed Prom aqueous s o l ~ ~ t i o n s

con ta in ing a little su lphur i c a c i d , w h i l e those which provide excellent

c o l o r a t i o n a r e appl ied i n t h e presence of ammoniim a c ~ t ~ t 7 < 4 r l r s l l l p h c ~ t i ' .

An in te rmedia te c l a s s i s formed by those dyed i n thc p r e w n c e of a l i t . t l e

a c e t i c a c i d , followed by a f i n a l a d d i t i o n of a s m a l l q u a n t i t y of su lphur i c

a c i d . These var ious methods are appl ied i n order t o promote an even

d i s t r i b u t i o n of t h e dye throughout t he f i b r e .

(ii) Basic Dyes

These are t h e hydrochlorides o r t h e z inc c h l o r i d e s a l t s of dyes

20.

13 having b a s i c groups , and a r e mainly triphenylrnethane d e r i v a t i v e s .

They a r e c h a r a c t e r i s e d as a c l a s s by t h e i r b r i l l i a n c e , b u t , t h e y arc n o t

f d s t t o l i g h t , and are only moderately f a s t t o washing. Eas ic dyes w i l l

dye p r o t e i n f i b r e s because sa l t - format ion can t ake place between the

p o s i t i v e i ons of t h e dye and t h e f ree carboxyl groups of '_he f i b r e . They

have no ~ i f f i n i t y f o r c e l l u l o s i c f i b r e s , b u t can be u s e d f o r dyeing t h e s e

by f i r s t t r e a t i n g t'ne f i b r e with a mordant, such a s t a n n i c a c i d . An

13 example of a b a s i c dye i s malachi te green (z) .

(iii) Mordant Dyes

The term "mordant dye113 i s app l i ed t o those dyes which can form

s t a b l e , insoluble complexes with m e t a l l i c hydrox ides . The oldest e x a q l e

of a mordant dye i s a l i z a r i n , which on account of t h e f a c t t h a t it gives

d i f f e r e n t l y co loured complexes with d i f f e r e n t meta l s i s s a i d t o be

po lygene t i c . A 1 imr i n w a s f o r n ~ c r l y u s c d for dyeing cotton mordantcd with

aluminium hydrox ide1 .

The modern mordant dyes may bc rcgarded a s specia l t ypes of acid

wool dyes, arid a r c normally rcferrc-d t o a s "mordant o r chrome dyes" .

2 1 .

They g ive h ighly coloured con~plexes with m e t a l l i c i.ons f a s t t o wet

t r ea tmen t , those of chromium being of p a r t i c u l a r i n t e r e s t from t h e p o i n t

of view of shade and a l l - round f a s t n e s s .

( i v ) D i rec t Dyes - 1

These a r e t h e most important dyes f o r c e l l u l o s i c f i b r e s , and a r e so-

c a l l e d d i r e c t dyes because they can be app l i ed without prev ious t rea tment

2 2 of t h e f i b r c with a mordant. Most of t h e direct dycs d re sodium r ; l ~ l . p h o r ~ t x t e

of complex a m compounds conta in ing two o r more a m grouFs. They are

app l i ed from h o t , aqueous solution to which i s added sodium c h l o r i d e t o

decrease t h e solubility of t h c dyc. The dycings may i n cer ta i -n cases

be given an a f t e r - t r ea tmen t with a copper salt t o improve f a s t n e s s t o

l i g h t o r d i a z o t i s e d and coupled with a n amine o r phenol t o improve f a s t n e s s

1 t o washing. An esamp1.e of a d i r e c t dye i s congo r ed ( 2 0 ) . - -.

(v) Vat Dyes

13 1 Examples of Vat dyes a r e ind igoid and anthraquinone dyes. They

a r e used f o r co lour ing a l l types of c e l l u l o s i c f i b r e s and have high

f a s t n e s s t o l i g h t and washing. I n d q o i s a l s o used f o r dyeing wool.

Vat dyes a r e insoluble I n water and m u s t f i r s t be converted i n t o a so lub le

form before they can be used f o r d y e i n g . Thi.5 i s u sua l1 y achieved !)y

reducing i n a l k a l i n e s o l u t i o n with sodium d i t h i o n i t e . The material is

14 t hen immersed i n t h e so lu t ion (leuco-conipound) , and o n cxposurc t o c i i x

o r on t rea tment w i t l i a chcruical ox id i s inq ;rqcnt. tkhr s c l u 1 , l e fol-rn % z

ox id i sed back to t h e dye i n and on the f i b r e . This is of course r e spons ib l e

f o r t h e h igh f a s t n e s s of v a t dyes t o washing. Examples of such dyes a r e

i nd igo (13) and a l i z a r i n ( 2 4 ) . - -

2.2 Anaular Phenothiazines

Angular phenothiazine r i n g system i s a phenothiazine r i n g system

wi th a fused benzene r i n g / r i n g s a t 1,2-, 3,4-, 6,7-, or 8 ,9 -pos i t i ons

of phenoth iaz ine ( 3 ) lead ing t o a benzo [Bl -phenothiazine (49) o r .- -

benzo [Clphenothiazine (50) . -

It i s a l s o p o s s i b l e t o g e t d ibenzo-der iva t ives , 51 and 52, where two - -

benzene r i n g s a r e fused i n any two of t h e p o s i t i o n s mentioned above.

2.2.1 Angular Phenoth iaz ine Precursors

Tn tllc s y n t h e s i s of angular he terocycl ic compounds various intornlcdiatc

conipounds are requi red . Some of these precursors a r e 0-aminothiopklenols

2 5 and t h c i r d r r i v a t i v e s . Most of the repor ted methods of prepa.ring fhcsc

0-;imonothiophenols a r e , however, ambiguous and charac te r i sed by low

25,26,27 y i v l d s . S(.verdl workers have reported t h e formation uf 1-IN.

2tc ttiiopltenol in poor y i e l d a s the zinc t h i o l a t e . Mital and J a i n irl l % ( J

rcpor ted the syn thes i s of ammothiophenols. An example of such amino-

thiophenol s i s 5-methyl-2-aminothiophenol (55) - which was preI,, ~ r e d by the

ac t ion of potassium thiocyanate on p-aminotoluene (53) i n presence of - 0

Gromlnc cir~d ( ~ l n ~ l d l ac.etic acld a t 0 . The r e s u l t i n g thiocyanilto p r o ~ l t ~ ~ t

(54) -- w d s 1iydrc)Lysec-I with potassiurrl hydroxide followed by n c u t r a l l s a t i o n

with glacial a c e t i c ac id .

(Scheme 4 ) .

Other precursors include the aminophenul, diarnino benzene and t h c i r

respec Live de r iva t ives . O-hinophenol (58) - was peparcd2 ' by the recl~lct ian

of o-nitrophenol (57a) - using sodium borohydride i n presence of pa11 , I ~ L I I I -

on - u l ~ a r c o ~ ~ 1 .

1 KOH

When p k ~ c n o l i s n i t r a t e d i n presence of s u l p h u r i c acid, mixt-urct uf

ortho- and para- p r o d u c t s - 57a and 57b respect ively was obtained. - Ilowevor , 0-n i t rophenol ( 57a) was predominant over the para-lxoductr . - The isomeric p r o d u c t s are readily separated by steam d i s t i l l a t i o n .

25.

The compounds, 3-arninopyr id ine-2 [ lH] -t.hione (63) - and 3-aminopyridine-

4 [ lH] - thione ( 64 ) , are a l s o of s y n t h e t i c I n t e r e s t i n the search f o r new -

aza-analogues o f t h e a n g u l a r p h e n o t h i a z i n e . Compound - 63 was p r e p a r e d by

30 Hoffmann rea r rangement of n ico t inamide wi th sodium h y p o c h l o r i t e .

The r e s u l t i n g 3- mino no-2-chloropyridine (61) - was ref luxed with potass ium

3 1 hydrogen s u l p h i d e i n p ropy lenc g l y c o l t o give compound - 6 3 i n good

yield. (Scheme 5 ) .

Scheme 5:

a:: 3 2

Kodig and coworkers r e p o r t e d a n explosion d u r i n g t h e - c o n v e r s i o n o f

n icot inarnide to 3-amino-2-chloropyrldine I6 - f ) . There fore t h e a l t e r n a t i v e

r o u t e i n v o l v i n g t h e convers ion of 3-aminopyridine compounds t o t h e

thiazolo [i ,4-b] p y r i d i n e d e r i v a t i v e s (65) 33 is p r e f e r r e d . The mercapto - compound 6 3 was then o b t a i n e d by r e f l u x i n g 65 i n a n a l k a l i n e mcdiurn -

Also refluxing 3-nitro-4-chloropyridine (66), - with alcoholic potassium

hybogen su lphide followed by the reduction of the nitro group35 will

give the desired hydrolysed product - 64.

(I,] t d c . KHS A

3 6 2-Amino-3-thiocyanato-6-picoline ( 6 8 ) w a s prepared by the a c t i o n -

of potassium thiocyanatc and bromine i n prcscncc of g l a c i d l acetic acid

as solvent on 2-amino-6-picoline (67). -

R e f l u x ing compound - 68 i n potassium l~ , -droxide gave the hydrolysed product ,

3 7 2-amino-3-mcrcapto-6-picoline (63) a f t e r a c i d i f i c a t i o n . The syn thes i s

38 u f t1,6-r] i , ~ ~ n i n o p y r i m i d i n e - 5 - t h i o l (70) , previously repor ted was achi c>vcd - by tllc ccL.i.uri of 40% potassium hydroxide on 4,6-diamino-5-thiocyanato-

pyr imid ine (71) - . Other der iva t ives of 70, were s i m i l a r l y prepared. -

G~rshon , Gref ig and ~ c a l a ~ ' reported t h e synthesisof 6-trif luororncthyl- 2,

4, 5- tr ichloro-pyrimidine (721 - by the action of phosphorus oxychloride,

phosphorus pentachloride and hydrochloric a c i d a l l i n gaseous phase on

6-trifl~orometh~l-5-chloro-2,4-dihydroxyPyrmide ( 7 3 ) . -

4 0 Synthesisrrf 1-~;ubstituted-4-amini~-~-halopyridaz-6-oncs was repurted .

The compound 74 - was prepared by the condensation of pher~, , , ~ y S r a z i n e w i t h

u n s a t u r a Led 1 , a-diketones or its do L 1 IT,^ t i ~ r e s with azot ropic rcnloval ul

water. Con~pound - 74 is refluxed in alcoholic potassium hydrogen sulphidc

((1 r j i w 75. -

> , (-Dichloro-l,4-naphthoquinone (80) 41,39

- whicll is une uf LIP,

mcilur uiterrncdiate compounds needed for this project was prepared by flr:;L

y t w e r a l i n g t f ~ ~ l 2-ethoxy-1,4-naphthoquinone ( 7 7 ) - as t h r x ~tdrtlnq III,LI cr I ,iL.

Co111~)ound -- '17 w ~ ~ s prepared by the reaction of ethanol in prcscncc. 0 E S U ~ L I I I I I

0 dic11ro111dLr. with 1,4-naphthoquinone (76) - at a te~nperature b e t w w n 75

a n d JO". C l ~ l o r i n d t ion of 77 in presence of fuscd sudium , I L . C . L , , I t . '111d - acetic id solution containing chlorine will givc 2-cl~loru- r I l ~ t l x y - I ,

I 1 o 1 1 r 7 - . Hydrolysis of (78) - y i v e s 2-r.11 1 , 1 , L I - i -llyJt oxy-1 , 4 1

4 - n c ~ p l i ~ l ~ u q ~ r inone (79) which reart L: v i ' ' I piiospl~or~~s c>:-:ychlor L A > , 1~11, ) : ? I ~ ~ I C J I I 1 , :

1,c.nt acl~lor i de and hydrochloric acid gds in yascous p1l;r:;r 1 CJ cr i vr3 :' , '1-

cl 1cll1o1 0 - 1 ,4-r1,ipl1t l~clqi~irlonc ( 0 0 ) . (Sclicnic L ) . -

Scheme (I:

2.2.2 - Syn t l ~ e t i.c Routes t o Angular-Phenothiazines

Thcrt! .ire v a r i o u s s y n t h e t i c r o u t e s t o a n g u l a r phenotlli;.izi.nes w l ~ i c : f ~

i n c lude c.orr(lensatiorr of t h e 0-aminothiophenol with var ious ndph.tholc!rit.

i i : . Reru thsen lo for i n s t ance i n 1"'9 p r e p a r e d 9-d ie t l l . 1 i~rnin. I - .

5 -p l i~ny l.iir~i nu-5H-benzo l a ] -pheno th iaz ine (83) with angnl . . , , , > n f i t I ~ i ~ i z i r i c , - Cl

r i n s l :;ysLt:ru. Coirlpound 83 i s a dark-green c r y s t a l m e l - t i n q at 235-4 1 . - I 1 w i l s p r c p r c d by adding dropwise 27ml of 10% po tass ium dir.hrorliti L r b

r-olut: ion t o ,1 mixtul:t\ of 2-an:ino-5-diethylamino tt*~ixc:ric I l-I i ,.111 1 ur- i.c

ac id ( U 1 ) , ~ - p l l c ~ i ~ l - l - n a p ~ ~ ~ ~ i y l a m i n e ( 82 , concentra tcd hydrocliLor i r. iic i d - -

IU.

and gl-acial a ce t i c ac id over a p e r i o d of 1 2 minutes a t room tcmperatlure.

'rhc r l ~ s u l l i n q b lue -g reen s o l u t i o n w a s s t i r r e d f o r 2 hours on the s t e a m

b a t h , cooled, made basic with ammonia and filtered.

4 4 9--l)ij,ro~,y L, lm ino-5-p-tolylimino-5H-benzo [a]phenothiazinc , (U.1) i t r ~ c l --

4 5 9-dirncthy 1 ami-no-5-phenylimino-5H-benzo [a] phenoth iaz i r~o ( > { 5 1 w c > r c i s i 111 i 1;) 1-1 y -

46 prcp;irc'd. Akatsuka and Yosll~r~aga i n their react ions of rluir!orrc:

conipourids w i L h 0-am i no th iophenols reported t he successful sy11 L hcs i s of

511-1 >nzo La] phcnothiazine-5-one (87) - . Compound U'r . 1 I ~ r c p a r ~ ! d by

2-Chloro- and 2 , 3 - d i c h l o r o - 1 ,4 -naph thoqu inones f o r m 6-chloro-SH-benzo

[alphenothiazine-5-one (88) - respectively when condensed w i t h 2-amino-

t h j o p h e n o l u n d e r t h e same r e a c t i o n c o n d i - t i o n s .

3-chloro-2-methoxy- and 3 -ch loro-2-11~c t l iy l - -~ur iva t - ives of 1,4.-naphthoquirlorle

a l s o unde rgo d e h y d r o c h l o r i n a t i v e and dehydrative c o n d ~ n s a t i o n respectively

with 2-aminoth iophenol to give t h e methoxy- (89) a n d methyl- (90)

drzrivat i v c s of the a n g u l a r phenothiazine. Similarly, 2-chloro- and

%,3-(I i c11Luro- 1 ,4-riaphthoquinone react with excess 2-an1inotlliophcno1 to

46 f o ~ I I I I ) c * I ~ : ~ o 1 , 1 1 - 1 , 4 - l w n z o f h i a z i n o [ 3 , 2 - ~ J p l l e n o t h i a z i n c ('11) - ---

Direct coupling of subststuted 0-amino th iopheno l with 2,3-d ic l i loro-1 ,4-

naphLlloclu inune (UO) - i n dry alcohol or d i m e t h y l f o r l n a r ~ i i d c ( D M F ) and i n

4 3 t I I C ' t r l ) : ; c ~ r ~ r : c ~ ( j f ' ,I bast h a s also been rcportcd by A g L l r w c l l and M i l . I l .

4 7 V ~ i n Al lLm dnd Rcynulds however, s u c c e s s f u l l y syn thes i zed colr~pounct - 91

by c o n d u n s i n g 2 moles o f 0 -amino th iopheno l w i t h 2,3-dicl~loru-l,4-napl1LI1~~-

qu inone i n d r y alrohol a t r e f lux ing t e m p e r a t u r e 47,48

A g a x w a l dnd M i . t a l 42,43

t r ied the s a m e r e a c t i o n in varirms s o l v c n t s ~ l : ; i ~ l q

vd r i o u s substituted 0-aminothiophenol_s a n d found that re, lsonat, l L y I ( $ 1 ti.:

w e r c Lrct~ i c m f ~ ~ l f by r u n n i n g t h e , L.action i n c t h o x y e t h a n o l , I - o l u c . ~ ~ ~ . ,

1 , L ,3- t r i u h l o r o - p r o p a n e , dimethylformamide a n d p y r i d inch roslbIait i vc.Ly.

I.'or t ~ ~ ~ ~ r ~ r l l l c ~ con~[)ound 95 wcls obtained in UC) b y i t ' l t i t I; I I '1 i r l t l 2, 1 - ~l 1 c . 1 1 l l r r 1 , - -

I ,4-naplit hoquinone with t h e s u b s t i t u t e d 0-aminnth inpht1nol i r ~ I Lu! [lrlvC I f ' r .

o f dry p y r I , I n e a s s o l v e n t .

When t h i s r e a c t i o n w a s t r i e d p r e v i o u s l y u s i n g t h r z i n c t h i o l a t e s of

4 2 subs t i . t , u ted aminotkiiophenol t h e y i e l d was low i n 1 ,I?, 3 - t r i c h l o r o p r o p a n e

as s o l v e n t , however, improved y i e l d was a c h i e v e d when p y r i d i n e or

dimethylformamide was used. Compound 97 i s prepared by r e f l u x i n g one -

mole of z i n c t h i o l a t e of substituted 0-aminothiophenol. wi th 2 , 3 - d i c h l o r o -

1.4-naphthoquinone i n dry pyridine or d imethy l formami.de.

Reynolds, Rdel and ~ a n R l l a n ~ ~ i n t h e i r i n v e s t i g a t i o n s on the r e a c t i v i t i e s

of N- (1,4-9ioxo-2-rnetl.,axynap~~thyl-3) pyr id in iun l salts w i t h a r o m a t i c amines

3 5 .

f o u n d t h d t when t h e p y r i d i n i u m sal t of the ndph thoqu inone - 99 o b t d l n c d by

t.r c l a t i r t c j 2-cl l lur o-3-n~cthoxy-1 ,4 -naphthoquinonc w i t h p y r i d Lnc I : I r ( . ( L C l c b t l

w i t l i 0 - - a ~ ~ r i n o t h i o p h ~ n o l i n alcohol, the p o l y n ~ ~ c l c i l r con~pounci 0 1 Lr, f o r - m c > t l

4 9 ' l 'ahL~l<ovx ~ I I J coworkkbrs c o n s i d e r e d t h e r c x t i o n to pr u c c c c l vicl ~ 1 1 ~ 1

36.

i n t e r m e d i a t e (101) which is r e a d i l y c y c l i z e d by t h e s c i s s i o n o f s u l f u r - -

s u l f u r bond upon t h e a t t a c k by t h e n u c l e o p h i l i c enaminone system.

(Scheme 7 ) .

Scheme 7: -

Z&y2z50 35 min

The r e d c r y s t a l s , which s e p a r a t e d on c o o l i n g from t h e r e a c t i o n m i x t u r e , sre

0 i n s o l u b l e i n most s o l v e n t s and a r e o f h i g h p u r i t y m e l t i n g a t 337-340 .

50 Phenylamino-der iva t ive of a n g u l a r p h e n o t h i a z i n e (104) - was p r e p a r e d

i n 58.8% y i e l d by condensing t h e s u b s t i t u t e d arninothiopl~enol z i n c s a l t (96 - )

w i t h 2-chloro-3-phenylamino-1,4-naphthoquinone (103) i n p y r i d i n e . The -

r e s u l t i n g p roduc t , 104 was reduced i n t he presence of sodium d i t h i o n i t e -

(Na S 0 ) t o form the reduced compound 105. 2 2 4 -

NHQh S 9 NHPh

I t h a s been r epqr t ed t h a t a t t a c h m q v a r l o u s s u L s t l tu ' tcd ethoxyanl l L i?c

I, 1 t o t h e benzophenothiazine molety w i l l i n c r e a x the chen!otherdpeutlc ~ 4 f e c t .

S u b s t i t u t e d 6-cthoxy;inil ino- SH-henzo [a pllcnoth~azin--S-oi~(: 1 10'7) ria :. -

synthes ized by t h e cyclocondensat ion of 2-chloro-3-ethoxyanilino-1,4-

5 1 naphthoquinone (106) - with z inc mercaptide of 2-aminothiophenol i n py r id ine .

R s tudy of t h e r e a c t i o n of naphthoquinone with va r ious n u ~ l e o ~ h i l e s ~ ~ has

l e d t o t h e s y n t h e s i s of an indandione d e r i v a t i v e of phenoth iaz ine .

0 The r e a c t i o n proceeded a t 25-30 i n a l coho l and a base t o g ive compound

109 which i s condensed with 2-aminothiophenol t o form compound 110. - -

(Scheme 8 ) .

Scheme 8:

39.

53,54 Thiona t ion r e a c t i o n h a s been r e c e n t l y reported ln t h e s y n t h e s i s

h i g h of a n g u l a r p h e n o t h l a z i n e . It i s a/temperature r e a c t i o r : o f powdered

s u l p h u r , iodine and naph thy l -b iphenylamhe i n the absence of s o l v e n t

r e s u l t i n g i n a mixture of Compounds 111 and 15 were s y n t h e s i z e d

by hea t ing I-naphthyl-3-biphenylamine ( l i 3 ) - prepared by t h e r e a c t i o n of

0 3-aminobiphenyl and 1-naphthol wi th s u l p h u r and i o d i n e a t 180 .

On the other hand, 2-naphthol r e a c t i n g with 3-aminobiphenyl under the same

c o n d i t i o n s gave a mixture of Linear and a n q u l a r p h e n a t h i a z i n e s .

5 4 S h i r l e y and coworkers i n t h e i r synthesis of nitrogen-mustard derivat ives

of benzo and dibenzo-phenothiazines have adopted t h e t h i o n a t ion r e a c t i o n

method t o prepare 1 2 1 . -

Compounds t 2 2 , 123, 124 and 125 were similarly p r e p a r e d as d e r i v a t i v e s o f 121 . --- - -

2.2 .3 R e a c t i o n s of Angular P h e n o t h i a z i n e s ---

Few reactions of the a n g u l a r h e t e r o c y c l i c compounds have been r e p o r t e d .

Angular p h e n o t h i a z i n e s undergo photochemi.ca1 s u b s t i t u t i o n r e a c t i o n 55 ,56

w i t h

a ldehydes giving v a r i o u s pho toproduc t s . For example when 5H-benzo [a]

phenothiazin-5-one and an a ldehyde i n benzene s o l u t i o n were i r r a d i a t e d

w i t h u l t r a v i o l e t l i g h t from 100 w a t t s h igh-prcssurc mercury lamp i n a

0 n i t r o g e n atmosphere a t 5 f o r 15 h o u r s and t h e n bubbled w i t h a i r for

5 5 s e v e r a l m i n u t e s , t h e p h o t o p m d u c t 126 was o b t a i n e d . -

Ueno and coworkersi6 i n I981 t r i c d t h e photochcrnical r e a c t i o n on t h e

amino- and a n i l i n o d e r i v a t i v e s o f t h e a n g u l a r p h e n o t h i a z i n e s and cane o u t

6 -Why lan i l~no-5H-benzo [ g l p h e n o t h i a z i n - 5 0 ( 130 ) on i r r a d i a Llon gave - 56

b - i l r ~ i l I 11~~-511- t )~~nzo [a] phenothiaxin-5-0r.e 131 . - --

5 7 Reynolds and coworkers reported t h e halogenat ion and nitration of

benzo[b]phenazine. They have shown that s u b s t i t u t i o n occurs exclusively

i n the 6 and 11-pos i t ions . When the compound - 132 was chlorinateds7 w i t h

sulf uryl chloride,

was obta ined .

t he product, 6,11-dichlorobenzo[b]phenazine (1331,

CL

0 ~ e n z o [ b ] p h e n a z i n e reacts with n i t r i c acid i n a c e t i c a c i d a t 95-100 to

5 7 g ive the d i n i t r o compound, 6 , l l -d.initrobenzo [b] p h e n a z i n ~ ! 134 . -

0 I f t h e n i t r a t i o n is conducted i n concentrated n i t r i c acid a t 95 , a

mononitrobenzo [blphenazine-6 , 1 I-quinone ( 135) is o b t a i n e d . This quinone -

i s also obtained by t r e a t i n g t h e d i n i t r o compound 134 with concentrated - n i t r i c acid a t 95".

I n t h e s y n t h e s i s o f a n g u l a r p h e n o t h i a z i n o l s , l4 58 r e d u c t i o n o f t h e

pheno th iazane d e r i v a t i v e s w i t h sodium d i t h i o n i t e was employed. 6-Ani l ino-

1211-benzo [a lpheno th iaz in -5-01 ( i 3 7 ) was p r e p a r e d by r e d u c t i o n of -

6-anilino-5H-benzo [a lphenothiazin-5-one (136) 56 with sodium d i t h i o n i t a

o r z inc d u s t .

19 Angular p h e n o t h i a z i n e s copolymerize w i t h c e l l u l o s i c coinpounds t o form

l i g h t s e n s i t i v e copying m a t e r i a l s used immensely i n pho tograph ic i n d u s t r i e s .

6 5 When added to polye thcr -based polyurethanes, t h e y a c t a s t h e r m l stabilizers .

For example, 5-hydroxy-12N-benzo[a]phenothictzinc (138) h a s been used as -

t h e r m a l s t a b i l i z e r f o r t h e p r o d u c t i o n of e l a s t o m e r s with polyurctl~ane .

Benzophenothiazines also react with alkylnitriles to form compounds

6 4 which when added to gasoline and petroleum lubricants act as antioxidants .

IH-Benzo [clphenothiazin-2-propionitrile ( - 140) was prepared63 by reacting

7H-benzo [clphenothiazine (139) - with propionitrile in glacial acetic acid,

heating for 1 hour and adding water to precipitate a yellow crystal melting

6 3 12H-Benzo [alphenothiazine (49) - reacts w r t h c e r t a l n heterocyclic a z ~ d e s

under the influence of heat or light to g l v e azomethane dyes in which the

coupling occurs at the 5-positions of - 49.

Compounct - 4 9 underqoes s i m i l a r r eac t ion w i t h pneny l ax idc unclcr t h ~ same

cond i t i on . Ani l ine i n presence of f e r r i c c h l o r i d e reacts with compound

49 t o g i v e the same r eac t ion product - 143 .

The r e a c t i o n tends t o proceed by the az ide gen ra t ing a n l t r e n e when it is

6 3 thermally decomposed . The ~ ~ i t r c n e , which i s a r e a c t i v e in te rmedia te

now attacks the compound - 49 to give the azo compound. (Scheme 1 0 ) .

Scheme 10 :

As we have seen, t h e chemistry of these angular h e t e r o c y c l i c

compounds is ma in ly domina ted by their s y n t h e s i s and r e a c t i o n s o f t h e

side c h a i n s . There h a s been e x t e n s i v e s t r u c t u r a l m o d i f i c a t i o n of these

s i d e - c h a i n s a imed a t improv ing both t h e i r b i o l o g i c a l and i n d u s t r i a l

< ~ p p l i c a t - i o n s . Thc un l imi t cc l cIc.~n;~nd for thc!sc a n g u l a r he tc : rocycl ic

compounds b o t h i n m e d i c i n e and i n d u s t r y h a s led u s to make a s t r 3 c t u r a l

m o d i f i c a ~ i o n i n v o l v i n g t h e i n t r o d u c t i o n of one o r more a n n u l a r nitroqen

;itorn/atoms i n t o t h e r i n q s y s t ~ r n l ead ing t o a n q u l a r a z a p h e n o t h i a z i n e s .

3. RESULTS AND DISCUSSION --

We have so f a r seen t h a t phenoth iaz ines and t h e i r aza-analogues have

h igh p o t e n t i a l i t y fo r use as dyes and pigments a n d for o t h e r i n d u s t r i a l

purposes . I t t h e r e f o r e , becomes necessary t h a t i nc reased r e sea rch

i n t e r e s t should be shown i n t h i s area of chemis t ry . This has l e d u s

t o syn thes i ze a new angular h e t e r o c y c l i c compound of this class with high

dyeing p o t e n t i a l . To prepare o u r target compound, 10-methyl-6-chloro-

11-,sza-5tI-benzo [ a ] phenothiazin-5-one ( 147 ) , we decided to start w i t h - 2-amino-6-picoline ( 6 7 ) - which is cheap and t h e r e f o r e r e a d i l y a v a i l a b l e .

The followings&eme was t h e r e f o r e proposed for the s y n t h e s i s of r h i s

new r i n g system. (Scheme 11 ) .

Scheme 11: --

3.1 2-Amino-3-thiocyanato-6-picoline ---

This compound w a s prepared by t h e a c t i o n of potassium th iocyana te

and bromine on 2-amino-6-picoline ( 67 ) - i n presence of glacial acetic

a c i d as so lven t .

Although t h i s compound (68) - was previous ly r epo r t ed by ~ k a f o e ~ ~ , we decided

t o modify t h e procedure t o ob ta in improved y i e l d s , we reac ted compound

67 with potassium thiocynnate in presence of bromine and g l a c i a l ace t ic 7

0 acid a t 0 and obta ined 68 i n 45 .5% as a g a i n s t 35% previous ly r ep r t ed . -

The u l t r a v i o l r t absorption spec t rum a£ 2-amino-3-thiocyanato-6-picoliile

(68) - showed no maxima i n the visible r eg ion , however, absorp t ion maxima

around 310 and 250 nm wore observed i n the-! uv region. ?'he i -nf ra red

- 1 spectrum of t h i s compound showed s t rong th iocyanate peak a t 2 1 4 5 c m .

The compound i s t r i s u b s t i t u t e d and snowed s t rong i n f r a r e d absorpt-ion

- 1 between 810 and 820 c m which is consistent with tlhir; : :ubs t . i t l~ t ion p a t t e r n .

The mechanism of t h i s r e a c t i o n probably proceeds by i n i t i a l attack

of 67 on t h e thiocyanogen . -

The presence of t h e ring n i t rogen of t h e pyridine d e a c t i v a t e s the r i n g

towards e l e c t r o p h i l i c a t t a c k . Rowever, s u b s t i t u t i o n t a k e s p l a c e , w i t h

d i f f i c u l t y , a t 3-posi t ion because s u b s t i t u t i o n a t t h i s p o s i t i c n l e a d s t o

5 9 t h e most s t a b l e Wheland in te rmedia te 149 . The a t t a c k at 2- and --

5 3 4-pos i t ions (150 and 151) r e s p e c t i v e l y are not favuurerl because each - -

has a canonicaL state i n which the p s s i t i v e charge is located on a h i q h l y

uns t ab le r i n g n i t rogen and t h i s l e a d s t o high energy s t a t e of the

in te rmedia te . When t h e p o s i t i v e charge i s loca t ed on a carbon atom of t h e

r i n q 149, art intermediate which is analogous to a t e r t i a r y carbonium ion - i s Eorn~ed with low energy s t a t e and a l s o high s t a b i l i t y .

The amino group at the 2 - p s i t i o n a l s o a c t i v a t e s the s ing thereby increasing

t he e l e c t r o p h i l i c center a t 3-position. The a t t a c k a t 4-position w i l l

l ead t o an intermediate which is not e n e r g e t i c a l l y favoured, t h e r e f o r e , t h e

thiocyanogen mounts a n electrophilic attack a t 3 - p s i t i o n which is the

e l e c t r o p h i l i c center forming a Wheland intermediate 148 . The proton -

of t h e intermediate 14U i s not set free a s s u c h , b u t is removed by t h e -

presence of a base and t h e intermediate then aromatizes tc t h e desired

product 68. -

The s t r u c t u r e of t h e product of t h e base-catalyzed reaction was a l s o

inves t iga ted .

68 - 6 9 -

When the 2-aaino-3-thiocyanato-6-picoline (68) - was ref luxed i n 20%

sodium hydroxide, followed by n e u t r a l i s a t i o n with glacial . a c e t i c a c i d ,

massive l i g h t greenish yellow p r e c i p i t a t e of 69 was formed. This compound, -

2-amino-3-mercapto-6-picoline (69) - was r e c r y s t a l l i s c d from methanol and

greenish yellow g l i s t e n i n g needles were co l l ec ted . Analysis of t h i s

product agrees with t h e molecular formula C H N S. e u l t r a v i o l e t 6 8 2

absorption spectrum showed no c h a r a c t e r i s t i c absorption i n the v i s i b l e

region, never the less , absorption maximum i n the uv region was shown around

305 nm. Compound - 69 is r e a d i l y soluble i n d i l u t e base and the disappearance

of t he peak a t 2145 Ern-' is an indica t ion t h a t the compound was hydrolysed.

- 1 A weak -SH absorption was expected between 21CO cm , absence of this

peak suggests that the compound exists i n the th ioketo f l ~ r m . This i s

- 1 further cornfirmed by the >C=Sabsarpti.an shown around 11913 crn -

Compound - 69 was probably formed by the hydroxyl ion mounting an i n i t l a l

nucleophi l ic a t t a c k on the thiocyano carbon leading t o an intermediate - 152

which picks up a proton t o form another interrnediatc 153 that rcarw2nrqcs -

to give 154. (Scheme 1 2 ) . -

Scheme 12: --

A second hydroxyl Lon now attacks t h e intermediate 154 a t the th ioamide -

carbon which then war ranges w i t h s trong c_.volution of ammonia. The

in te rmedia te 156 which was formed qu ick ly r e a r r a n g e s with evolut~un of -

carbon d i o x i d e t o g l v e the d e s i r e d hydrolysed product (69) i n 9 2 % y i e l d . -

r><l .

1.3 1 O-MPL 1iy L-6-cliloro-1 I. -aza-5H-bcnzo [ a l p h e n o t h i a x A i n - 5 - m t t - -- ' I ' l l i :; i - ~ ~ ~ c ! . ion w . ~ s t r i c d in several s o l v c n t s ndrnc.Ly u ~ ~ ~ c ) T . L ~ ~ - u ~ I I I ,

i i mc8l hy l.formL>~!lide and benzene r e s p e c t i v e l y . The react ion d ic l n o t l-aF:t-

p 1 ~ i ( : t \ i n chlorof or111 because both reactants were i n s o l u b l e i 1.1 t- lie solvent. .

In b c * r i ~ c . t - i c > alone, because both r e a c t a n t s were insoluble i t bcc;mP

d i EF i c : u 1 t for the rcac t ion to take place at ref l u x . W 1 i t . n I l r c :

c l . i r n c d llyl for~lt,l~~ii.d[-. was used d l o n e as the r c a c t i u n so lvc~r i t , i ~ o l - l i

1 ) t ( ~ ~ ~ . f , b ~ , ! : ; w i ~ t - v ~ ~ U ~ I I ~ J I . ~ : , b u t the r e f l u x i n g t c ! ~ p c ~ r i ~ . t ~ ~ r t ~ 0 1 - 1 1 0 w.1:; I ~ J L I

h i g h lead ing to t h e decompos i t ion of the p r o d u c t . A ni ixt rurc of ix?ri;:enc

and climcthylformamide i n the r a t i o 20 : 1 was then t r i e d at r e Flrlxi n g

L) I r ~ t r I . w n 7 d 7 &!id t h e r t . ac . t i un w.1:; : ;uc:c: r%:; : ; l I I l .

0 , ~ n d I I I P ~ L:; at)~.)ve 301) . 'lhe e l e m e n t a l a n a l y s i s is i n agrctcrat:nt. w i t h t l ~ r ?

niu! ~ , ~ , u l c i t - forrr~ula C H N SOCl and t h e molecu la r weight i s 312. 5 . T'ha 6 9 2

111 t r a v i u 1 t l l s p c c t r u r l ~ showed no maxima i n t h e v i s i b l c . t-egiun , lmwcvr:r,

characleristic a b s o r p t i o n maxima were shown around 278 and 245 nlti.

- 1 The ir s p e c t r u m showed c h a r a c t e r i s t i c C30 a b s o r p t i o n around I , , 4 U cm

and t h i r; i s the c h d r a c t e r i s t i c C=O a b s o r p t i o n for ~ ~ l 1 c n o 3 t l i a z i n c

- 1 O I I I U ~ '!'he C=N s t r e t c h showed a b s o r p t i o n pedk a t 1505 C I I ~ w 1 1 i l ~ ~

L l 1 c 1 (1-11 tx~rrcli .~~g f r c . q u c ~ ~ c y gave c h a r a c t e r i s t i c a l ~ s o q ~ l i o r l ! , ( . I wc.l . tr

1300 and 1 W O ern-'. The peaks between 1138 and 1278 cm-I rlrc duc t o

- 1 C-N anti C-C s t r e t c h i n g f r e q u e n c i e s and t h e a b s o r p t i o n a r o ~ m d 700 cm

is a ct1i1 r ~ c t e r i s t i c a b s o r p t i o n o f an a l k y l c h l o r i d c -

A s w a s s t a t e d e a r l i e r t h e compound 147 w a s i n s o l u b l e i n alrrlost .a11 - the orgclnic s o l v e n t s , n e v e r t h e l e s s , it w a s s l i g h t 1 y s o l u b l tn i

, ~c t - t -o r~ t l . ' I ' I I C N W spectrum of t h e compound was thcrcfort., rulr i r l

de~1tc.r. I I ctl a c e t o n e . The spectrum showed a s i n g l e t pc~~ll.. ..I t 6 1 . !, . I~IJ

a rr1111Li~)lt~L down field between 7.2 a n d 7.4&. ?'he i n t c q r a l v;llcir?>;

:;howr>d t 1 1 , -P protons. a t 61.5 and s i x p r o t o n s for the rlownfittl it L l c ~ r l r 1

7 - 2 I / 4 ' U ~ i s is i n agreement with thc dst;iqncld r : t r u c t ltrr..

' r ' l l (> f urrn,lt ion of compound, 10-met_hyl-6-~1iloro-Il-~~-.~ - , I l - h ~ ~ i ~ ~ ~ o 1 I 1

pflenotkiiaz~n-5-one (147) - probab ly p roc~ cis by , n i C u l ' t t t a ~ k uf tllv

mercapto compound by t h e sodium carbondte gene ra t i ng d mercap t ide - 157

G 0 w11ick1 t tlcn rriounts a nucleophilic attack on the c h l o r i n e dtum of t l i e

nciph thoc l~~ irtone for-ming a naphthylpyridyl su lphide (1 - 58) . (Schcrnc 1 3 ) .

The amino group i n t u r n mounts a n u c l e o p h i l i c a t t a c k on t h e c a r b o n y l

c e n t e r forming an i n t e r m e d i a t e 159 which r e a r r a n g e s t o g i v e 160. mere - -

is e l e c t r o n s h i f t and e l i m i n a t i o n of wate r molecule t o g ive t h e compound,

Produc t 147 was s u b j e c t e d t o v a r i o u s chemical r e a c t i o n s namely - r e d u c t i o n w i t h sodium d i t h i o n i t e l * and t rea tment with 2 .4- r l in i t rophenyl

h y d r a z i n e t o form t h e hydrazone d e r i v a t i v e .

3.4 Reduct ion of l0-methyl-6-chloro-ll-aza-5H-benzo[a]phynothiazin-5-one ---------------------

Reduct ion o f l0-methyl-6-chloro-lI-aza-5H-benzo[a]phenothiazin-5-one

( 147 ) w a s ach ieved by r e a c t i n g it wi th sodium d i t h i o n i t e I n t h e presence -

of wate r a t an e l e v a t e d tcmpcraturc.

The purple-brown c o l o u r o f t h e s t a r t l n g compound - 147 g r a d u a l l y changed

t o c ~ ~ l o u r l e s s a t t h e end o f t h e r e a c t i o n , which on f i l t r a t i o n gave a

purple-brown p r e c i p i t a t e . T h i s p r e c i p i t a t e on a n a l y s i s w a s found t o

be the s t a r t i n g material ( 1 4 7 ) . -

The reaction proceeds th rough the a t t a c k of free r a d i c a l hydrogen

g e n e r a t e d by h e a t i n g sodium d i t h i o n i t e i n w a t e r , on the carbonyl c e n t e r

of 147 leading t o a n o t h e r free radical i n t e r m e d i a t e (162) . This i n t e r - --

mediate q u i c k l y picks up a n o t h e r free radical hydrogen and r e a r r a n g e s

t o give t h e product ( - 16 1 ) . (Scheme 14) .

'I'hu r ~ d u c t c d form ( 16 1 ) which is colourLess and hence less e x t e r i s i v c l y - con jucjo t t t d W i l : i o x i d i z ~ d back t o 147 on exposure to atmospheric oxygcn . -

'l'hi:, is the p r i n c i p l e on which vdc dyeing works. l ' k t e dye is a j -q~ l led ~ t i

the reduccd form a n d is allowed t o be oxidized by ~ tn io !_ ;p l~ r i r i c o:iycjclrl.

The u l t r a v i o l e t absorption spect rum of t h e compound :I661 showed - maxima i n uv r e g i o n around 335 and 350 nm and a minimum a t 295 nm.

The i n f r a r e d absorption spectrum of t h e compound (166) - showed n i t r o

- 1 group absorption between 1500 and 1580 c m . The asymmetric n i t r o

g r o u p of aronatic and t h e C-N s t r e t c h i n g frequency showed absorpt ions

- 1 a t 1520 and 850 c m r e spec t ive ly i n t h e i r spect rum of compound (166) --

The r e a c t i o n p roceeds by t h e hydrazinc mounting a n u r l c o p h i l i c

Scheme 15:

3 . 6 APPLICATION OF THE DYESTUFF - --

Before a compound qua l i f ies as a d y e s t u f i , i t - h a s Ln a d d i t i o n to

be o b t a i n a b l e cheaply t o possess c e r t a i n properties namrly, h l g h degree

of fastness t o both light: and chemicals such as d e t e r g e n t s a n d secondly ,

its ability t o leave pcrnnncnt c o l o u r a t i v r , when it is a p p l i e d . I t 3 s

trhereicrt., ncccssary t o car ry o u t some eval i la t r o n tests to v e r i f y whcthcr

conpound 1.37 meets thesc- s>ccclficatior --

3.6.1 Dyeing of White Fabr ic Mater ia l

3 The recipe f o r dyeing of white f a b r i c m t e r i a l incl-udes 20 m l of

ace tone , 0 . 2 g of t h e dyes tu f f ( i .e compound - 147) and 3 square cen t ime te r

of white fabric m a t e r i a l weighing 0.10 q . The mixture was al lowed to

0 s t a y f o r about 45 minutes a t a temperature of 50 . A purple-brown shade

was l e f t on t h e white f a b r i c a f t e r drying a t room tempera ture .

The dyed m a t e r i a l was i roned both dry and w e t r e s p e c t i v e l y and was

found t o bc f a s t t o i r o n i n g . It Mas s p o t t c d wi th concen t r a t ed ammonia

s o l u t i o n and one molar ammonium carbonate r e s p e c t i v e l y and was e q u a l l y

found t o be f a s t t o a l k a l i n e . However, when 5M n i t r i c acid and d i l u t e

hydrochlor ic acid were spo t t ed on t h e dyed material it was found n o t t o

be fast to a c i d . The dye m a t e r i a l was e q u a l l y exposed t o s u n l i g h t

be o u r s o f 9 am and 3 p m for a pe r iod o f one week and it showed

fascness rro s u n l i g h t . It was f i n a l l y soaked i n a soap s o l u t i o n f o r about

two hour s , r i n s e d with water and d r i e d a t room temperature. It was

found also t o be fast to soap s o l u t i o n .

The compound i s found t o be an excellent d y s t u f f because of t h e

beautiful shade it gives t o t h e dyed f a b r i c material as w e l l as the

encouraging r e s u l t s ob ta ined from t h e f a s t n e s s e v a l u a t i o n tests

(<,hart 1 ) .

3.6.2 Compounding o r Shoe polish

bb I n compounding the shoe p o l i s h , t h e r e c i p e g iven below was heated

on a hot plate stirrer and stirred

Candle wax

Petroleum j e l l y

Kerosine

Pigment (dyes tuf f 1

Melon sccd oil

A homogenous s o l u t i o n was obta ined

Eor 2 hours at 6a0.

0.5 c j

1.00 g

2-00 m

0.04 g

1.00 m,

Thi s s o l u t i o n w a s allowed r;o s c l . at

room temperature. The p o l i s h was used on a brown leather and it leEt

a po l i shed and sh in ing su r f ace on t h e l e a t h e r m a t e r i a l . I t i s t h e r e f o r e ,

a good pigment f o r making brown shoe p o l i s h .

3 . 6 . 3 Recipe f o r p repa ra t ion of Varnish

The rccipc for 6 1

o n of varn ish i n c pcd o i l ( 3 . 5 g ) I

pigment ( d y e s t u f f ) O , L g aria acetone (1.0 m l ) , all s t i r r e d v igorous ly f o r

4 hours a t room tempera ture . A t t h e end of t h e s t i r r i n g , a homogenous

s o l u t i o n was ob t a ined which was used t o p o l i s h some wooden s u r f a c e s .

It is e q u a l l y found u s e f u l i n t h e p r e p a r a t i o n of wood va rn i shes .

3.7 ACUTE TOXICITY TEST TO DETEWINE THE LD50 OF 10-METHYL-6-CHLORO-

Because of t h e i n d u s t r i a l a p p l i c a t i o n s o f t h i s s y n t h e t i c product

( d y e ) , it i s very necessary t o carry o u t an a c u t e t o x i c i t y t e s t 6 2 t o

determine i t s s a f e t y l i m i t s . LD50

i s t h e concen t r a t i on ( i n mg/kg) of t h e

compound which w i l l cause t h e dea th of 50% of t h e an imals used f o r t h e

t e s t . In our own experiment , we used f i v e groups of a d u l t mice with each

group c o n s i - s t i n g of s i x a~icc!. ' l ' l~c' compound W;LS disycrscd i n "tween U O "

as t h e s o l v e n t and each animal i n each group was g iven equa l dose of t h e

dye ( i n mg/kg) meant fir t h a t group and t h e r e s u l t i s given i n t a b l e 1.

Table 1 shows t h e r e s u l t of an a c u t e t o x i c i t y tes t t o determine t h e LD 5 0

of l0-methyl-6-chloro-ll-aza-5H-benzo[alphenothiazin-5-one.

Table 1: Resu l t s of Acute Tox ic i ty T e s t t o Determine the LD oE 5 0

N o of animal Percentage of Correc ted Group Dose (mg/kg) Log Dose

t h a t d i ed dead animals Percentage

When no dea th is recorded a t zero percentage of dead an imals , a

c o r r e c t i o n f a c t o r i s in t roduced which i s used t o e s t i m a t e t h e percentage of

6 2 animals t h a t d i e d . Thi s i s given as 08 of dead animals = 100 x - 2 5 where

n

n i s t h e number of animals i n each group. Therefore , 0% of dead animals

The graph of t h e log of t h e doses a r e p l o t t e d a g a i n s t t h e percentage

of the animals t h a t dicd. From t h e s t r a i g h t l i n e graph t h a t wa.s ob ta ined

t h e dose ( i n mg/kg) of t-he compouncl t h , i i k i 1 l c t i 5 0 ~ of t hc. s n i r ~ l ~ j l i ; in

t h a t group can be obta ined . From our graph, t h i s corresponds t o l og dose

of 1.60 which i f convcrLed is e q u a l t o 39.81 mg/kg. LDS0 f o r t h i s

compound i s t h e r e f o r e 39.81 mg/kg.

Considering the f a c t t h a t t h i s compound is h igh ly in so lub le i n most

s o l v e n t s , it becomes d i f f i c u l t f o r t h i s l e t h a l dose of 39.81 mg/kg

q u a n t i t y of t h e dyes tuf f (147) t o be a s s i m i l a t e d i n t o t h e body system of -

any human being i f used a s a dye f o r f a b r i c s . Therefore, it i s presumably

nontoxic.

Because it is reasonably nontoxic, it i s highly recommended f o r use a s

pigment f o r compounding cosmetics such a s l i p s t i c k s eyeshadow e t c .

Apart from i t s use f o r dyeing f a b r i c ma te r i a l s , it i s recommended

a s colourant i n some ed ib le foods and confect ionery such a s chewing

gum and sweets.

In conclus ion, it is highly recon~mended f o r use both f o r ornamentals

and e d i b l e foods. Also because of i t s probably unlimited a p p i i c a t i o n s ,

research i n this area of chemi-s t ry should be highly encouraged.

0.50 1.00 1-50 2.00

L o g d o s e Fig. Determination of L 400f 10- methyl- 6- chloro- Il - m a - 5H -

benzo Col phenothiaz in-5-one. G r a p h of O/O of a n i m a l s d e a d against Loglo dore

4. EXPERIMENTAL

4 . 1 General

Melting p o i n t s were determined with Electro- thermal melt ing p o i n t

appa ra tus i n open c a p i l l a r i e s and a r e uncorrec ted . uv abso rp t ion s p e c t r a

were measured with a Pye unicam sp 8000 spectrophotomctcr i n methanol

us ing matched 1-cm q u a r t z cells. Tile a b s o r p t m n Imxlrrla h1:re cjlvcn ~ 1 s

l o g E va lues . I R s p e c t r a were measured wi.th a Pye unicam sp 1000

spectrophotometer and NMR was measured with a Varian Assoc ia tes T-60 nmr

spectrophotometer .

0 r, H& $QC. Aco H

oO H J

This compound (68) .- w a s prepared by modifying t h e p rev ious ly descr ibed

3 6 method . A one l i t r e three-necked f l a s k equipped with a mechanical

s t i r r e r , a thermometer and surrounded by an ice-bath ( s a l t and i c e )

was charged wi th 2-amino-6-picoline (67) - (21.6 g , 0.2 moles) and g l a c i a l

0 a c e t i c a c i d (200 1 1 1 1 ) p r ev ious ly cooled t o 5 . M e c h x ~ i c a l stirring

0 cont inued u n t i l t h e temperature came down t o 0 . Potassi-urn th iocyana te

(160 g , 1 .64 moles) was added. Bromine (32 m l ) i n 120 ml of g l a c i a l

0 a c e t i c a c i d i n r eagen t b o - t t l e p rev ious ly cooled t o 0 was added i n

d r o p l e t s from a dropping funnel a t such a r a t e t h a t t h e temperature never

0 r o s e above 0 over a pe r iod of 3 hours . S t i r r i n g cont inued f o r 2 hours

a f t e r bromine a d d i t i o n and f o r a d d i t i o n a l 10 hours a t room tempera ture .

I t was l e f t t o s t and over n i g h t .

Bo i l i ng water (100 m l ) was added t o t h e orange s l u r r y and hea ted

t o 80° and f i l t e r e d h o t . The b r i g h t orange r e s idue was washed with two

p o r t i o n s of 50 m l each of b o i l i n g g l a c i a l a c e t i c a c i d and f i l t e r e d h o t .

The combined f i l t c r a t e was neu- t ra l izcd with concent;rat.ed a ~ x n o n i a so lu t ior i

t o a p H 7-8 t o g ive t h e d e s i r e d product .

White need le s of 2-~mino-3-thiocyanato-6-picoL~i1c (68) - iilclt~ncrj

More p roduc t s were c o l l e c t e d by keeping t h e n e u t r a l i z e d s o l u t i o n a t a

0 temperature 0-3 f o r s e v e r a l days. The p recau t ions taken and t h e technique

l e d t o increased y i e l d (15 g , 45 .5%) compared with t h e p rev ious ly r epo r t ed

3 6 352 y i e l d .

uv ..Amax 250 (3.791, 310 (3.78)

ir (potassium bromide) 3400, 3180, 2 1 4 5 , 1665, 1590, 1490, 1400, 1350, 1200,

3 'L ' l l i s cornpound (69) - was p r e p a r e d by a p r e v i o u s l y rclported ~ n c . l . l w d -

2-Amino- 3-thiocyanato-6-picoline (3.30 g , 0.02 moles) w a s added i n t o a

one l i t r e three-neck f l a s k equipred w i t h a r e f l u x condcrlsc!r. Scil i urn

s u l f i l l c ( ? CJ, 0.01 mole) was added and t h e rnixturi ' was r c f l u x e d i r i 30 1 1 1 1

of 20':- p o t a s s i u m h y d r o x i d e s o l u t i o n o n a h e a t i n g mant le fo r 8 i lours .

The d a r k - . l)rown s o l u t i o n w a s t r e a t e d . w i t h activated c:harcoal , boi lc?d f u r ;.in

aiic3.i.tic~rl.ll 15 minutes and I l ' i l t e r e d h u i . The yellowisl-A-1.irown : ~ , , . L u t i c ~ n wds

c-:oolecl, r l c k k l L r - d l i z e d w i t h g l a c i a l a c e t i c a c i d and c l l i l l e d . ' l ' l icx yc. I I o w i : A 1

1" , , c i p i 1-.,.I( (1 obLdilleci was c o l l e i t-ed by f i l t o r a t i u n a n d r c,c:t:ys( .I I 1 i zc.ti

f r o n l i l q ~ ~ u s ~oetrhanol-acetone m i x t u r e . N o r i t was added and a q c e e n ish

yrfiow cr-y:;l , t l o f the dipolar : : L : L t of 2-aniino-3-nier-cc~~)t o-C>-l) i 1 1 i 1 1 ( ( . I \ ) ) . -

(1.30 g , ) . , b t a i n e d , m . p . 245O.

U v . 305 ( 3 . 7 4 )

I t ~ J L I S , I q r dual colour devc,~opn. . n t ; it w a s i n i . t . i a 1 . L ~ c) r - , l l l ( l c* i / t ' l low,

Ljutr d E t c r r ', r l i i h c ~ i c ~ t h ~ : ,cll.~jl.rr changed L o ~ ~ i o w r ~ i d - y c . 1 1 ow < 1 1 1 i t I i I L J L J 7

~ ~ u r p l c urowll. When t.here was no f u r t h 6 . r c o l u u r c l ~ a r ~ r j c , i l c : w i , ~ 1 1 ( t 111 ixl trr c ,

w<: . r t ! l l u x at. I l u t terrlpcrature f o r a total. of 6 i l ou r : ; . '1'111, > : I ( , L i ( o 1 1

1 : ; , . I 8 , . j . - . . . . . - . . . - . .

-.---,- , , , , . .

, . # , , . . . , . . . . . , . . . .

. , , , , , , , . . . , , , I 1 . I , . I

, . ! i . , , I - - ! . .

c , , < , , . . . . . , . . . j : I . : ! . , . . , ,

' I I : ! : : ; : , . . . . - - , . - . I : , . ' I , . , . , . . - . 8 . . ' 1 : : I . . ' . : . , .

v e s s e l was c h i l l e d and l a t e r f i l t e r e d . To t h e s o l i d r e s i d u e i n a b s a k e r ,

250 m l of water was added t o d i s s c h c tile i n o r g a n i c m a t e r i a l s , s t i r r e d and

f i l t e r e d . The purple-brown p r o d u c t o b t a i n e d w a s r e c r y s t a l l i z e d i n a c e t o n e

0 m e l t i n g p o i n t above 300 . The y i e l d w a s 1.55 g ( 9 9 % ) .

uv: Xmx 278 ( 3 . 8 9 ) , 245 ( 3 . 8 0 ) , 315 (3 .58)

ir (KBr) 3400, 3200, 1648, 1590, 1480, 1400, 1350, 1280, 1190, 1150,

8 2 0 , 7 5 0 , 700 cm-l.

nmr (Acetone-d6) 61 -50 s (3-CH3) , 67.2-7 - 4 (m) (6-H) . Anal. c a l c d f o r C H N SOC1: C , 61.44; H,2.90; N,8.96; S.10.25;

16 9 2

C1,11.33; Found C , C l . G l ; H,3.01; N,U.91; S,10..32; C1,11.20.

T h i s r e a c t i o n 1 4 was c a r r i e d o u t u s i n g o 50 m l round-bottom f l a s k

equ ipped w i t h a ref Lux concier~scr . 1 0-Metl~yl -G-chloro-11-am-5H-bcnzo [a]

- t, phenoth iaz in -5-one (0 .02 g , 6 . 4 x 10 mole) , sodium d i t h i o n i t e ( 2 9 ,

0.015 m o l e ) , acetone ( 2 5 ml) and. 2 drops of DMSO were put 3-11 the f l a s k

a n d r c f Lux ror 1 llo~ir. There w a s no change b u t e v o l u t i o n of hydroqcbll

sulpliitlc. gas W~*S observed. Wel-er ( 3 ml) was added a d t h e purple-brown

c-olo~lr ~ r l u n c d L , A Lcl y c h a n g e d t o l i g h t yellow and subseyucbnt Ly 1 o c o l o u l l c - s s .

This was r c f l u x e d tor additional 1 hour , f i l t e r e d h o t under s u c t i o n . The

c o l o u r l u s s f i l t e r a t e changed t o l i g h t yel low and t hen t o pu rp l e -b rown .

The product was p r e c i p ~ t a t e d wi th wa te r , i s o l a t e d dnd found t o bc

1 0 r r ~ c , l l ~ y l C,-c:lll orr)-1 l-~za-5tI-L~~rizo [ a ] p I l e r ~ o L l i i c ~ z j n - ~ ~ I I( \ .

4 -6 10-Mc~thyl-6-chloro-11-aza-5H-benzo [alpheno t l ~ l a z ~ n - 5 - ( 2 , l - d i n ~ L r o - -- - - - - - phcnyl) hydrazone.

f o r 10 minutes and was d i l u t e d c a r e f u l l y wi th M-H SO ?'he pu rp l e s o l i d 2 4 '

p roduc t (166) was c o l l e c t e d by s u c t i o n f i l t r a t i o n and washed i n a l i t t l e -

aqueous methanol. The product i s l0-methyl-6-chloro-ll-aza-5H-benzo[a]

uv: Amax 335 (4.16) , 350 (4.15) Amin 295 (4 -00)

i r ( K B r ) 3420, 3300, 1650, 1525, 1420, 1370, 1330, 1256 , 1140, 1060,

4 .7 Determinat ion of LDr jo of 10-1neth~l-6-chloro-ll-aza-~~-benzo[a]

phenothiazin-5-one i n mice (Tox ic i t y t e s t ) bL

Five groups o f a d u l t mice were used f o r t h e experiment . Each group

c o n s i s t of a t l e a s t s i x mice. 10-Methyl-6-chloro-11-aza-bendalpheno-

thiazin-5-one ( 1 4 7 ) - d i s p e r s e d i n "Tween 80" and i n j e c t e d i n t o t h e m i c e i n

doses o f 2 .5 , 5 - 0 , 10 -0, 20.0 and 40.0 mg/kg r e s p e c t i v e l y i n groups 1 t o

5. Equal t r ea tmen t was adminis te red t o t he animals by nlaking s u r e t h a t

t h e volunie of t h e s o l u t i o n was k e p t c o n s t a n t . The number of animals dead

w i t h i n 24 hours a f t e r t h e animals were i n j e c t e d were recorded f o r each

group.

Resu l t :

No of animal Percentage of Corrected Group Dose (mg/kg) Log Dose

- tha t died dead animals % dead

5. BIBLIOGRAPHY -

E . K i l n e r and D.M. Samuel, "Applied Organic Chemis t ry" , MacDonald and Evans L t d . , London, (1Y60), pp. 422-470.

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E. R. Trotman, "Dyeing and Chemical Technology o f Textile Fibres" 4 t h ed. riffi in, London, (19701, pp 368-443,

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W.E. Long, G e r . Of fen . , 2 , 9 0 ? , 4 3 8 ( 1 9 7 8 ) ; Chern. Abstr. 9 3 , - 7378% ( 1980) .

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J, Shigehara and H. Tsuchida, Japan Kokai Tokkyo Koho - 8 0 , 40,798 (1980) ; Chem. Abstr., 93, 73775 (1980) .

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G. Mann, S. Hauphmann, I I . W i L d e and J . Lehmann , Naumann, Manfrtxd -- G e r . ( E a s t ) 139 ,268(1973) ; Chem. Abstr., 3 3 , 151568(1380) . - - -

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