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Synthesis of 2-Cinnamoyl-l,3-indandione Derivatives and their Reactions with Hydrazine, Hydroxylamine Hydrochloride, Thiourea, Secondary Amines and Diethyl Oxalate

E l - S a y e d A f s a h , F a t h y A b d e l K a d e r A m e r a n d H a s s a n E t m a n

Chemistry Department, Faculty of Science, Mansoura University, Mansoura, A. R. Egypt Z. Naturforsch. 84b, 502-506 (1979); received October 25, 1978 2-Cinnamoyl-1,3-indandione Derivatives

A series of 2-cinnamoyl-l,3-indandiones (2a-e) were obtained by condensing 1 with aldehydes. Treatment of 2 a with hydrazine or hydroxylamine hydrochloride gave 2-(5-phenyl-2-pyrazolinyl or -isoxazolinyl)-1,3-indandione (3 and 5) respectively, and when treated with thiourea gave 2-(6-phenyl-2-thioxo-4-pyrimidinyl)-l,3-indandione (6).

The formation of 2-(/3-piperidino-, -morpholino- and -arylmercaptohydrocinnamoyl)-1,3-indandiones (7a-b and 8a-b) from 2 a was investigated. Compound 7 b when treated with hydrazine gave 9. The 2-(a,/?-dimorpholinohydrocinnamoyl) derivative (11) was obtained by the action of morpholine on the dibromo derivative (10). The Michael condensation of 2 a with ethyl acetoacetate or acetyl acetone was investigated. Treatment of 1 with benzaldehyde in (3:1) molar ratio gave 14, which reacted with diethyl oxalate to give 15. Cyclization of 15 with polyphosphoric acid lead to the formation of 16.

I n v i e w o f t h e r e p o r t e d b i o l o g i c a l a c t i v i t y o f

2 - a r y l - l , 3 - i n d a n d i o n e d e r i v a t i v e s i n t r e a t m e n t o f

t h r o m b o s i s [ 1 - 3 ] , as a n t i i n f l a m m a t o r y a g e n t s [4],

a n d m i t i c i d e s [5]. 2 - C i n n a m o y l - l , 3 - i n d a n d i o n e s [6]

(2) r e p r e s e n t a n a d a p t a b l e s t a r t i n g m a t e r i a l f o r t h e

i n t r o d u c t i o n o f h e t e r o c y c l i c m o i e t i e s i n t h e 2-

p o s i t i o n o f 1 , 3 - i n d a n d i o n e , a n d f o r t h e s y n t h e s i s o f

s o m e n e w h e t e r o c y c l i c b i n a r y s y s t e m s , w h i c h h a v e

d e m o n s t r a t e d b i o l o g i c a l a c t i v i t y i n d i f f e r e n t a r e a s

o f c h e m o t h e r a p y .

T h e r e f o r e , C l a i s e n - S c h m i d t c o n d e n s a t i o n o f 2-

a c e t y l - 1 , 3 - i n d a n d i o n e (1) w i t h t h e a p p r o p r i a t e

a r o m a t i c a l d e h y d e g a v e t h e c o r r e s p o n d i n g 2-c in-

n a m o y l - l , 3 - i n d a n d i o n e s ( 2 a - e ) .

0 0 0 0 1 2a: R = C6H5

b: R = C 6H 4 • OCH3-p c : R = C6H3 • (OCH3)-2,4 d: R = C6H4 • N(CH3)2-P e: R = C 6 H 4 -N0 2 -^

Since 1 was reported to react with hydrazine to give 3-methylindeno[l,2-c]pyrazol-4(l H)-one [7], while a./?-unsaturated ketones react to give pyrazo-lines [8]. Therefore, in the present study, our first interest was focussed on the reaction of 2 a with

Requests for reprints should be sent to Dr. E. M. Afsah, Faculty of Science, Mansoura University, Mansoura, A. R. Egypt. 0340-5087/79/0300-0502/$ 01.00/0

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

r e a c t a s 1 , 3 - d i k e t o n e o r a s a ,/?-unsaturated k e t o n e .

T h e c o n d e n s a t i o n o f 2 a w i t h h y d r a z i n e w a s c a r r i e d

o u t i n a 1 : 1 m o l a r r a t i o w i t h e l i m i n a t i o n o f o n e

m o l e c u l e o f w a t e r t o g i v e 2 - ( 5 - p h e n y l - 2 - p y r a z o l i n -

3-y l ) - 1 , 3 - i n d a n d i o n e (3 a).

3a: R = H 4 b: R = CO • CH3 c: R = S02 • C6H5

C o n f i r m a t o r y e v i d e n c e f o r s t r u c t u r e 3 a is p r o v i d e d

bjr e l e m e n t a l a n a l y s e s a n d s p e c t r a l d a t a . T h e

u l t e r n a t i v e s t r u c t u r e 4 w a s r u l e d o u t , b e c a u s e t h e

I R s p e c t r u m o f 3 a s h o w a b s o r p t i o n s a t 3065

( e n o l i z e d C O ) a n d 1 6 7 0 c m - 1 (/3-diketone), a n d l a c k

t h e a b s o r p t i o n b a n d o f t h e i n d e n e r i n g c a r b o n y l .

T r e a t m e n t o f 3 a w i t h a c e t i c a n h y d r i d e - a c e t i c a c i d

m i x t u r e , o r b e n z e n e s u l p h o n y l c h l o r i d e i n p y r i d i n e

a f f o r d e d t h e N - a c e t y l a n d N - b e n z e n e s u l p h o n y l

d e r i v a t i v e s (31) a n d c).

S i m i l a r l y , t h e r e a c t i o n o f 2 a w i t h h y d r o x y l a m i n e

h y d r o c h l o r i d e i n p y r i d i n e g a v e 2 - ( 5 - p h e n y l - 2 - i s o x a -

z o l i n - 3 - y l ) - 1 . 3 - i n d a n d i o n e (5). O n t h e o t h e r h a n d ,

c o n d e n s a t i o n b e t w e e n 2 a a n d t h o u r e a i n a 1 : 1 m o l a r

r a t i o a f f o r d e d 2-( 1 , 2 , 5 , 6 - t e t r a h y d r o - 6 - p h e n y l - 2 - t h i -

o x o - 4 - p y r i m i d i n y l ) - 1 , 3 - i n d a n d i o n e (6). T h e I R

E. S. Afsah et al. • Synthesis of 2-Cinnamoyl-l,3-indandione Derivatives 503

s p e c t r u m o f

(3448 c m - 1 ) ,

( 1 6 7 0 c m - 1 ) ,

a n d N - C = S

T h e a d d i t i v e p r o p e r t y o f t h e c o n j u g a t e d ( C = C ) i n

2 a ; p r o m p t e d u s t o i n v e s t i g a t e i t s b e h a v i o u r

t o w a r d s t h e a c t i o n o f s e c o n d a r y a m i n e s . T h u s ,

t r e a t m e n t o f 2 a w i t h p i p e r i d i n e a n d / o r m o r p h o l i n e ,

a f f o r d e d 2 - ( / 5 - p i p e r i d i n o - o r - / 5 - m o r p h o l i n o h y d r o c i n -

n a m o y l ) - l , 3 - i n d a n d i o n e ( 7 a - b ) , r e s p e c t i v e l y . T h e

I R s p e c t r a o f 7 s h o w e d a b s o r p t i o n s a t 3 0 6 0 a n d

1 6 7 5 c m - 1 e n o l i z e d C O a n d /5-diketone a n d a t

1 5 7 0 c m - 1 (te/^-nitrogen). S i m i l a r l y , c o n d e n s a t i o n

o f 2 a w i t h t h i o p h e n o l o r p - t h i o c r e s o l g a v e t h e

c o r r e s p o n d i n g 2 - ( / ? - a r y l m e r c a p t o h y d r o c i n n a m o y l ) -

1 , 3 - i n d a n d i o n e ( 8 a - b ) .

7a: X = CH2

b: X = O ia: R = H b: R = CH3

T r e a t m e n t o f 7 b w i t h h y d r a z i n e i n b o i l i n g

m e t h a n o l , a f f o r d e d 3 - ( / ? - m o r p h o l i n o p h e n e t h y l ) - i n -

d e n o [ l , 2 - c ] p y r a z o l - 4 ( l H ) - o n e (9). T h e s t r u c t u r e o f 9

w a s a s s i g n e d f r o m i t s c o r r e c t a n a l y t i c a l d a t a a n d

t h e e x h i b i t i o n o f C O s t r e t c h i n g a t 1 6 9 5 c m - 1 a n d

N H s t r e t c h i n g a t 3400 c m " 1 .

A d d i t i o n o f b r o m i n e i n c a r b o n t e t r a c h l o r i d e t o 2 a

y i e l d s 2 - ( a , j S - d i b r o m o h y d r o c i n n a m o y l ) - l , 3 - i n d a n d -

i o n e (10) . I t s I R s p e c t r u m s h o w e d b a n d s a t

3 0 6 5 c m - 1 ( e n o l i z e d C O ) , 1 6 6 5 c m - 1 ( ß - d i k e t o n e )

a n d 6 9 5 c m - 1 ( C - B r ) .

I n v i e w o f t h e r e p o r t e d r e a c t i o n o f d i b r o m o -

c h a l c o n e s w i t h m o r p h o l i n e t o g i v e a . ß - d i m o r p h o l i n o

I n o r d e r t o e x p l o r e t h e s y n t h e t i c p o t e n t i a l i t i e s o f

c o m p o u n d s 2 a s i n t e r m e d i a t e s f o r t h e p r e p a r a t i o n

o f 2 - s u b s t i t u t e d - l , 3 - i n d a n d i o n e s , t h e M i c h a e l c o n -

d e n s a t i o n o f 2 a w a s p e r f o r m e d . T h u s , e t h y l a c e t o -

a c e t a t e o r a c e t y l a c e t o n e w a s c o n d e n s e d w i t h 2 a i n

b o i l i n g b u t a n o l u s i n g p i p e r i d i n e a s c a t a l y s t t o g i v e

2 - ( 4 - e t h o x y c a r b o n y l - o r 4 - a c e t y l - 3 - o x o - 5 - p h e n y l - l -

c y c l o h e x e n - l - y l ) - l , 3 - i n d a n d i o n e ( 1 2 a - b ) , r e s p e c -

t i v e l y . T h e s t r u c t u r e s o f c o m p o u n d s 1 2 a r e b a s e d o n

e l e m e n t a l a n a l y s e s a n d I R s p e c t r a . F u r t h e r m o r e ,

h y d r o l y s i s a n d d e c a r b o x y l a t i o n o f 1 2 a g a v e 2 - ( 3 - o x o -

5 - p h e n y l - 1 - c v c l o h e x e n - 1 - y l ) - 1 , 3 - i n d a n d i o n e (13) .

S t r u c t u r e o f 1 3 w a s c o n f i r m e d t h r o u g h i n d e p e n d e n t

s y n t h e s i s , b y c o n d e n s a t i o n o f b e n z y l i d e n e a c e t o n e

w i t h 1 .

2 a Ethyl acetoacetate

or/ acetyl acetone

12 A : R = COOC2H5

B : R=CO.CH3

Benzylideneacetone

O n t h e o t h e r h a n d , c o n d e n s a t i o n o f 1 w i t h b e n z -

a l d e h y d e i n 3 : 1 m o l a r r a t i o , l e a d t o t h e f o r m a t i o n

o f 2 , 2 ' - ( 3 - p h e n y l g l u t a r y l ) d i - l , 3 - i n d a n d i o n e (14) .

T h e I R s p e c t r u m o f 1 4 i n d i c a t e d b a n d s c h a r a c t e r -

i s t i c o f t h e e n o l i z e d C O a t (3050 c m " 1 ) , ( 1 6 7 5 c m " 1 )

ß - d i k e t o n e a n d ( 1 4 3 0 c m - 1 ) - C H 2 - C O - [ 1 1 ] . I n

p a r t i c u l a r , t h e f o r m a t i o n o f 1 4 is c o n f i r m e d t h r o u g h

i n d e p e n d e n t s y n t h e s i s , b y c o n d e n s a t i o n o f 2 a

w i t h 1 .

6 s h o w e d b a n d s a s s i g n e d t o N H

e n o l i z e d C O (3070 c m - 1 ) , ß - d i k e t o n e

C = N ( 1 6 1 5 c m - 1 ) , C = S ( 1 3 4 0 c m - 1 )

( 1 5 3 5 c m - 1 ) .

d e r i v a t i v e s [9, 10]. T h e d i b r o m o - d e r i v a t i v e 1 0 w a s

t r e a t e d w i t h m o r p h o l i n e t o g i v e 2 - ( a , / ? - d i m o r p h o l i n o -

h y d r o c i n n a m o y l ) - 1 , 3 - i n d a n d i o n e ( 1 1 ) .

504 E. S. Afsah et al. • Synthesis of 2-Cinnamoyl-l,3-indandione Derivatives 504

I n v i e w o f t h e r e p o r t e d f o r m a t i o n o f 3 , 5 - d i e t h o x y -

c a r b o n y l - 4 - p h e n y l c y c l o p e n t a n e - l , 2 - d i o n e , b y D i e c k -

m a n n c o n d e n s a t i o n o f d i e t h y l o x a l a t e a n d d i e t h y l

/?-phenylg lutarate [12], c o m p o u n d 14 w a s c o n d e n s e d

w i t h d i e t h y l o x a l a t e in presence o f s o d i u m e t h o x i d e

t o g i v e 2 , 2 ' - [ ( 4 , 5 - d i o x o - 2 - p h e n y l - l , 3 - c y c l o p e n t y -

l e n e ) d i c a r b o n y l ] d i - l , 3 - i n d a n d i o n e (15). S t r u c t u r e 15 w a s i n f e r r e d f r o m t h e c o r r e c t a n a l y t i c a l d a t a , a n d

i t s I R s p e c t r u m w h i c h s h o w s a b s o r p t i o n b a n d s a t

(1730 c m - 1 ) 1 , 2 - d i k e t o n e (f ive-ring), 1 6 7 0 c m - 1 ) ß-d i k e t o n e a n d t h e d i s a p p e a r a n c e o f t h e - C H 2 - C O -

b a n d . C o m p o u n d 15 u n d e r w e n t c y c l i z a t i o n o n t r e a t -

m e n t w i t h p o l y p h o s p h o r i c a c i d t o g i v e 1 3 - p h e n y l -

n H - d i i n d e n o [ 2 , l - e : 2 ^ ' , e ' ] c y c l o p e n t a [ 2 , l - b : 3 , 4 - b ' ] -d i p y r a n - 1 1 , 1 2 , 1 4 , 1 5 ( 1 3 H ) t e t r o n e (16). S t r u c t u r e 1 6

w a s a s s i g n e d f r o m i ts c o r r e c t a n a l y t i c a l d a t a a n d

t h e e x h i b i t i o n o f i n d e n e C O a t 1 7 0 5 c m - 1 a n d t h e

p y r one C O a t 1660 c m - 1 .

E x p e r i m e n t a l

A l l m e l t i n g p o i n t s a r e u n c o r r e c t e d . I R s p e c t r a w e r e r e c o r d e d in K B r o n a U n i c a m S P 2000 I n f r a r e d S p e c t r o p h o t o m e t e r .

2- Cinnamoyl-1,3-indandiones (2) F e w d r o p s o f p i p e r i d i n e w e r e a d d e d t o a m i x t u r e

o f 1 (0.02 m o l ) , a n d t h e a p p r o p r i a t e a l d e h y d e (0.02 mol) , in 50 m l w-butanol . A f t e r r e f l u x i n g f o r 6 h , p r o d u c t 2 t h a t s e p a r a t e d o n c o o l i n g w a s

c r y s t a l l i z e d f r o m b e n z e n e - e t h a n o l , in 5 0 - 6 0 % y i e l d . T h e r e s u l t s are g i v e n in T a b l e I .

2-(5-Phenyl-2-pyrazolin-3-yl)-l,3-indandione (3a) T o a s o l u t i o n o f 2 a (0.005 mol) in 60 m l b e n z e n e -

e t h a n o l ( 1 : 1 ) , h y d r a z i n e ( 9 8 % ) (0.005 m o l ) w a s a d d e d . T h e r e a c t i o n m i x t u r e w a s r e f l u x e d f o r 6 h. T h e p r o d u c t o b t a i n e d a f t e r c o n c e n t r a t i o n a n d c o o l i n g w a s filtered a n d r e c r y s t a l l i z e d f r o m e t h a n o l .

C o m p o u n d 3 a f o r m e d y e l l o w c r y s t a l s ; m . p . 2 1 5 ° C ; y i e l d 8 2 % .

C18H14N2O2

F o u n d C 74.22 H 4.80 N 9.43, C a l c d C 74,46 H 4.86 N 9.65.

C o m p o u n d 3 b w a s o b t a i n e d b y h e a t i n g 3 a (0.5 g) in 30 m l a c e t i c a c i d - a c e t i c a n h y d r i d e ( 1 : 1 ) f o r 1 h . T h e p r o d u c t o b t a i n e d o n d i l u t i o n w i t h w a t e r w a s c r y s t a l l i z e d f r o m m e t h a n o l .

C o m p o u n d 3 b f o r m e d o r a n g e p o w d e r ; m . p . 263 °C d e c . ; y i e l d 7 6 % .

C 2 OH 1 6 N 2 0 3

F o u n d C 84.27 H 5.50 N 9.66, C a l c d C 84.47 H 5.67 N 9.85.

C o m p o u n d 3 c w a s o b t a i n e d b y a d d i n g benzene-s u l p h o n y l c h l o r i d e (0.5 m l ) t o a s o l u t i o n o f 3 a (0.4 m l ) in p y r i d i n e (30 ml) . A f t e r r e f l u x i n g f o r 1 h, t h e r e a c t i o n m i x t u r e w a s d i l u t e d w i t h w a t e r . T h e p r o d u c t o b t a i n e d w a s c r y s t a l l i z e d f r o m m e t h a n o l .

C o m p o u n d 3 c f o r m e d o r a n g e p o w d e r ; m . p . 2 8 0 ° C d e c . ; y i e l d 6 8 % .

Table I. 2-Cinnamoyl-l,3-indandiones (2a-e).

Compound m.p. Yield Formula Carbon [ % ] Hydrogen [ % ] Nitrogen [ % ] [°C] [ % ] Found Calcd Found Calcd Found Calcd

2 a 1 8 2 5 0 C I 8 H 1 2 0 3

2 b 180 55 C19H14O4 2 c 1 4 2 5 7 C 2 O H I 6 0 5

2 d 1 8 6 5 1 C 2 O H I 7 N 0 3

2e 246 62 C i 8 H u N 0 5

78.13 78.24 4.18 4.37 74.23 74.49 4.46 4.60 71.39 71.41 4.66 4.79 75.11 75.21 5.13 5.36 4.16 4.38 67.20 67.28 3.31 3.45 4.08 4.35

E. S. Afsah et al. • Synthesis of 2-Cinnamoyl-l,3-indandione Derivatives 505

C24H18N2O4S

F o u n d C 66.78 H 4.08 N 6.30 S 7 . 2 7 , C a l c d C 66.96 H 4 . 2 1 N 6.50 S 7 .44 .

2-(5-Phenyl-2-isoxazolin-3-yl)-1,3-indandione (5) T o a s o l u t i o n o f 2 a (0.005 m o l ) in 50 m l p y r i d i n e ,

h y d r o x y l a m i n e h y d r o c h l o r i d e (0.005 m o l ) w a s a d d e d . A f t e r r e f l u x i n g f o r 6 h, t h e r e a c t i o n m i x t u r e w a s d i l u t e d w i t h w a t e r . T h e p r o d u c t o b t a i n e d w a s c r y s t a l l i z e d f r o m e t h a n o l .

C o m p o u n d 5 f o r m e d o r a n g e c r y s t a l s ; m . p . 184 °C d e c . ; y i e l d 7 8 % .

C18H13NO3

F o u n d C 74.06 H 4 .33 N 4.67, C a l c d C 7 4 . 2 1 H 4.49 N 4.80.

2- (1,2,5,6-T etrahydro-6-phenyl-2-thioxo-4-pyrimidinyl)-1,3-indandione (6)

A m i x t u r e o f 2 a (0.005 m o l ) , t h i o u r e a ( 0 . 0 0 5 m o l ) ; p o t a s s i u m h y d r o x i d e (0.5 g) , e t h a n o l (100 m l ) a n d w a t e r (2 m l ) w a s r e f l u x e d f o r 3 h. T h e p r o d u c t f o r m e d o n c o n c e n t r a t i o n a n d c o o l i n g w a s filtered, w a s h e d w i t h w a t e r , d r i e d a n d c r y s t a l l i z e d f r o m e t h a n o l .

C o m p o u n d 6 f o r m e d y e l l o w c r y s t a l s ; m . p . > 3 0 0 ° C ; y i e l d 4 1 % .

C19H14N2O2S

F o u n d C 68.07 H 4 . 1 3 N 8 . l l S 9 .34, C a l c d C 68.24 H 4 . 2 1 N 8.37 S 9 .58.

2- (ß-Piper idino- or ß-morpholino-hydrocinnamoyl)-1,3-indandione (7)

A s o l u t i o n o f 2 a (0.005 m o l ) a n d p i p e r i d i n e or m o r p h o l i n e (0.005 m o l ) i n 50 m l d r y b e n z e n e s t i r r e d a n d h e a t e d a t 60 °C f o r 30 m i n . T h e r e a c t i o n m i x t u r e w a s a l l o w e d t o s t a n d o v e r n i g h t a t r o o m t e m p e r a t u r e . L i g h t p e t r o l ( b . p . 4 0 - 6 0 °C) w a s a d d e d , a n d t h e p r e c i p i t a t e d so l id w a s filtered a n d c r y s t a l l i z e d f r o m b e n z e n e - e t h a n o l .

C o m p o u n d 7 a f o r m e d y e l l o w n e e d l e s ; m . p . 1 8 5 ° C ; j d e l d 4 7 % .

C23H23NO3

F o u n d C 76 .22 H 6.27 N 3 . 6 7 , C a l c d C 7 6 . 4 3 H 6.41 N 3.87.

C o m p o u n d 7 b f o r m e d y e l l o w p o w d e r ; m . p . 1 9 0 ° C ; y i e l d 5 3 % .

C 2 2 H 2 I N 0 4

F o u n d C 72.48 H 5 .67 N 3.70, C a l c d C 7 2 . 7 0 H 5 .82 N 3.85.

2- (ß-Arylmercaptohydrocinnamoyl )-1,3-indandione (8)

T o a s o l u t i o n o f 2 a (0.005 m o l ) i n 50 m l d r y b e n z e n e w a s a d d e d (0.005 m o l ) o f t h i o p h e n o l or p - t h i o c r e s o l , f o l l o w e d b y 2 d r o p s o f p i p e r i d i n e . T h e r e a c t i o n m i x t u r e w a s h e a t e d a t 60 °C f o r 30 m i n , a n d a l l o w e d t o s t a n d o v e r n i g h t a t r o o m t e m p e r a -t u r e . L i g h t p e t r o l ( b . p . 4 0 - 6 0 °C) w a s a d d e d , a n d

t h e s o l i d t h a t s e p a r a t e d w a s filtered a n d c r y s t a l l i z e d f r o m m e t h a n o l .

C o m p o u n d 8 a f o r m e d p a l e y e l l o w c r y s t a l s ; m . p . 1 9 5 °C.

C24H18O3S

F o u n d C 7 4 . 3 3 H 4 . 5 8 S 8.02, C a l c d C 7 4 . 5 8 H 4 . 6 9 S 8.29.

C o m p o u n d 8 b f o r m e d y e l l o w c r y s t a l s ; m . p . 1 1 0 °C.

C25H20O3S

F o u n d C 74 .90 H 4.88 S 7 .83, C a l c d C 7 4 . 9 7 H 5 .03 S 8.00.

3-( ß-Morpholinophenethyl )indeno[ 1,2-c]-pyrazol-4( 1H)-one (9)

T h e e x p e r i m e n t a l p r o c e d u r e d e s c r i b e d f o r t h e s y n t h e s i s o f 3 a w a s a d o p t e d . C o m p o u n d 9 w a s f o r m e d i n 6 7 % y i e l d .

C o m p o u n d 9 f o r m e d y e l l o w n e e d l e s ; m . p . 1 7 8 °C.

C22H21N3O

F o u n d C 7 6 . 7 1 H 5 . 9 7 N 12.06, C a l c d C 7 6 . 9 4 H 6 . 1 6 N 1 2 . 2 3 .

2-(a.ß-Dibromohydrocinnamoyl)-1,3-indandione (10) C o m p o u n d 1 0 w a s o b t a i n e d b y a d d i n g b r o m i n e

(0.005 m o l ) t o a s o l u t i o n o f 2 a (0.005 m o l ) i n c a r b o n t e t r a c h l o r i d e 60 m l . T h e s o l i d o b t a i n e d o n c o n c e n t r a -t i o n w a s filtered a n d c r y s t a l l i z e d f r o m m e t h a n o l .

C o m p o u n d 1 0 f o r m e d p a l e y e l l o w n e e d l e s ; m . p . 160 ° C ; y i e l d 8 5 % .

C i 8 H i 2 0 3 B r 2

F o u n d C 4 9 . 4 3 H 2.48 B r 36 .55 , C a l c d C 4 9 . 5 7 H 2 . 7 7 B r 36.64.

2- (a,ß-Dimorpholinohydrocinnamoyl )-1,3-indandione (11)

T o a s o l u t i o n o f 1 0 (0.003 m o l ) i n 80 m l m e t h a n o l w a s a d d e d (0.007 m o l ) o f m o r p h o l i n e . T h e r e a c t i o n m i x t u r e w a s h e a t e d f o r 30 m i n , a n d a l l o w e d t o s t a n d o v e r n i g h t a t r o o m t e m p e r a t u r e . D i l u t e a c e t i c a c i d w a s a d d e d a n d t h e s e p a r a t e d s o l i d w a s c r y s t a l l i z e d f r o m m e t h a n o l .

C o m p o u n d 1 1 f o r m e d o r a n g e c r y s t a l s ; m . p . 205 ° C ; y i e l d 7 7 % .

C26H28N2O5

F o u n d C 69.38 H 6 . l l N 6.08, C a l c d C 6 9 . 6 2 H 6.29 N 6.24.

Condensation of 2 a with ethylacetoacetate and acetyl acetone

A s o l u t i o n o f 2 a (0.01 m o l ) , e t h y l a c e t o a c e t a t e or a c e t y l a c e t o n e (0.01 m o l ) , i n 5 0 m l w - b u t a n o l , c o n t a i n i n g o n e m l p i p e r i d i n e , w a s r e f l u x e d f o r 8 h . T h e r e a c t i o n m i x t u r e w a s a d d e d t o d i l u t e h y d r o -c h l o r i c a c i d , t h e p r o d u c t so f o r m e d w a s f i l t e r e d a n d c r y s t a l l i z e d f r o m b e n z e n e e t h a n o l .

C o m p o u n d 1 2 a f o r m e d d a r k y e l l o w c r y s t a l s ; m . p . 80 °C d e c . ; y i e l d 5 2 % .

506 E . S. Afsah et al. • Synthesis o f 2-Cinnamoyl- l ,3- indandione Der ivat ives 506

C 2 4 H 2 0 O 5

F o u n d C 7 4 . 1 9 H 5 . 0 1 , C a l c d C 7 4 . 2 1 H 5 . 1 9 .

C o m p o u n d 1 2 b f o r m e d y e l l o w c r y s t a l s ; m . p . 240 ° C ; y i e l d 6 1 % .

C 2 3 H l 8 0 4

F o u n d C 76 .90 H 4.88, C a l c d C 77 .07 H 5.06.

2- (3-Oxo-5-phenyl-l-cyclohexen-l-yl) -1,3-indandione (13)

C o m p o u n d 1 3 w a s o b t a i n e d f r o m 1 2 a i n 4 6 % y i e l d , b y h y d r o l y s i s w i t h h o t 5 % a q u e o u s s o d i u m h y d r o x i d e , f o l l o w e d b y d e c a r b o x y l a t i o n w i t h b o i l i n g d i l u t e h y d r o c h l o r i c a c i d .

T h e s a m e c o m p o u n d w a s a l s o o b t a i n e d b y M i c h a e l c o n d e n s a t i o n o f a n e q u i m o l a r m i x t u r e o f b e n z y l i d e n e a c e t o n e a n d 1 . T h e e x p e r i m e n t a l p r o c e -d u r e d e s c r i b e d f o r t h e s y n t h e s i s o f 2 w a s a d o p t e d ; y i e l d 4 9 % .

C o m p o u n d 1 3 f o r m e d y e l l o w c r y s t a l s ; m . p . 2 3 2 ° C ( b e n z e n e ) .

C21H16O3

F o u n d C 79 .58 H 5.00, C a l c d C 7 9 . 7 2 H 5.09.

2,2'-(3-Phenylglutaryl)di-l,3-indandione ( 14)

T o a s o l u t i o n o f 1 (0.03 m o l ) a n d b e n z a l d e h y d e (0.01 m o l ) i n 80 m l ? i - b u t a n o l , p i p e r i d i n e o n e m l w a s a d d e d . T h e r e a c t i o n m i x t u r e w a s r e f l u x e d f o r 20 h . T h e p r o d u c t t h a t o b t a i n e d a f t e r c o n c e n t r a t i o n w a s c r y s t a l l i z e d f r o m b e n z e n e - e t h a n o l .

C o m p o u n d 1 4 f o r m e d v e l l o w p o w d e r ; m . p . > 3 0 0 ° C ; y i e l d 7 3 % .

C29H20O6

F o u n d C 74 .78 H 4 . l l , C a l c d C 74.98 H 4.34.

T h e s a m e c o m p o u n d w a s a l s o o b t a i n e d i n a 4 6 % y i e l d , b y t h e c o n d e n s a t i o n o f a n e q u i m o l a r m i x t u r e o f 2 a a n d 1 , a c c o r d i n g t o a p r o c e d u r e s i m i l a r t o t h e a b o v e o n e .

2,2'-f ( 4,5-Dioxo-2-phenyl-1,3cyclopentylene )-dicarbonyl]di-l,3-indandione (15)

T o a s o d i u m e t h o x i d e s o l u t i o n ( p r e p a r e d f r o m 0.2 g o f s o d i u m m e t a l a n d 60 m l o f e t h a n o l ) w a s a d d e d (0.0025 m o l ) o f d i e t h y l o x a l a t e a n d (0.002 m o l ) o f 14 . T h e r e a c t i o n m i x t u r e w a s s t i r r e d f o r 2 h , t h e n r e f l u x e d f o r 6 h. T h e p r o d u c t t h a t o b t a i n e d after-d i l u t i o n w i t h w a t e r a n d n e u t r a l i z a t i o n w a s f i l t e r e d , a n d c r y s t a l l i z e d f r o m b e n z e n e - e t h a n o l .

C o m p o u n d 1 5 f o r m e d y e l l o w c r y s t a l s ; m . p . 2 1 0 ° C ; y i e l d 5 5 % .

C31H18O8

F o u n d C 7 1 . 6 5 H 3.33, C a l c d C 7 1 . 8 1 H 3 .49.

Cyclization of 1 5 with polyphosphoric acid A m i x t u r e o f 1 5 (1 g) a n d p o l y p h o s p h o r i c a c i d

(10 g) w a s h e a t e d f o r 1 h a t 1 1 0 °C. T h e r e a c t i o n m i x t u r e w a s d i l u t e d w i t h 100 m l w a t e r , a n d t h e s o l i d o b t a i n e d w a s f i l tered, a n d c r y s t a l l i z e d f r o m b e n z e n e - e t h a n o l .

C o m p o u n d 1 6 f o r m e d o r a n g e p o w d e r ; m . p . 1 7 0 ° C : y i e l d 6 8 % .

C31H14O6

F o u n d C 77 .02 H 2 . 8 1 , C a l c d C 7 7 . 1 7 H 2.92.

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(1940). [10] N. H . Cromwell , J . A m . Chem. Soc. 63, 2884

(1941). [11] R . Silverstein and G. Bassler, Spectrometric

Identif ication of Organic Compounds , p. 107. John Wi ley & Sons, Inc. , N. Y . 1968.

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