Development of novel pyrazolones by using SiO2/ZnCl2 – green approach

Article abstract of DOI:10.1007/s12039-019-1679-5

Abstract: The present research work deals with the green synthesis of substituted pyrazolone derivatives 4(a–f) from 2,4-dinitrophenylhydrazine with various substituted aromatic aldehyde and ethyl acetoacetate in the presence of silica-supported zinc chlo

Full text of DOI:10.1007/s12039-019-1679-5

J. Chem. Sci.
( 2 0 1 9 ) 1 3 1 : 1 0 5
Ó I n d ia n A c a d e m y o f S c i en c es
h t tp s :/ / d o i . o r g/ 1 0 . 1 0 0 7 / s 1 2 0 3 9 - 0 1 9 - 1 6 7 9 - 5 Sadhan
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REGULAR ARTICLE
Development of novel pyrazolones by using SiO2/ZnCl2 – green
approach
a
G N E E L I M A , K L A K S H M I a n d K S E S HA M A HE SW A R A M M A
b
c ,
*
a
J N T U , A n a n t h a p u ra m u , A n a n t a p u r , I n d i a
D e p a rt m e n t o f P h a rm a c e u t i c a l A n a l y s i s , S r i V e n k a t e s w a r a C o l le g e o f P h a r ma c y , R V S N a g a r , C h i t t o or ,
A n d h r a P ra d e sh 5 1 7 1 2 7 , I n d i a
b
c
D e p a r t m e n t o f C h e m i s t r y , J N T U C o l l e g e o f E n g in e e r i n g ( A u t o n o m o u s ) P u l i v e n d u l a , P u l i v e n d u l a ,
A n d h r a P ra d e sh 5 1 6 3 9 0 , I n d i a
E - m a i l : k a l l u r u m a h i . c h e m i s t r y @j n t u a .a c .i n
M S r e c e i v e d 1 J u ne 2 01 9 ; r e v i s e d 1 2 J u l y 2 0 1 9; a c c e p t e d 1 2 J u l y 2 0 1 9
Abstract. T h e p r e s e n t r e s e a r c h w o r k d e a l s w i t h t h e g r e e n s y n t h e s i s o f s u b s t i tu t e d p y r a z o l o n e d e r i v at i ve s
4( a–f) f ro m 2 , 4 - d i n i t r o p h e n y l h y d r a z i n e w i t h v a r io u s s u b s t i tu te d a r o m a ti c a l d e h y d e a n d e t h y l a c e t o a c e ta t e i n
t h e p r e s e n c e o f s i l i c a -s u p p o rt e d z i n c c h l o r i d e ( S i O / Z n C l ) a s a r e c y c l a b l e L e w is a c i d c a t a l y s t . T h e s y n -
2
2
1
t h es i z e d c o m p o u n d s w e re s t r u c t u ra l l y c h a r a c t e r i z e d w i t h I R , H N M R , M a s s s p e c tr a a n d e l e m e n t a l a na l y s i s .
A l l t h e s e c o m p o u n d s w e r e t e s t e d f o r t h e ir a n t i o x i d a n t a c t i v i ty b y u s i n g t h e D P P H r a d ic a l s c a v e n g i n g m e t h od .
Keywords. P y r a z o l o n e ; s i l i c a -s u p p o r te d z i n c c h l o r i d e c a t a l y s t ; g r e e n s y n t h e si s ; a n t i - o x i d a n t a c t i v i t y .
1. Introduction
i n h e re n t l y s a f er d e s i g n o f m o l e c u l e s , m at er i al s , p r o d -
2
u c t s , a n d p r o c e s s . I n h e t e r o c y c l i c c o m p o u n d s, t h e
G r e e n c h e m i s t r y i s ‘‘ th e u ti l iz a t i on o f a s e t o f p r i n c i p l e
t h a t e l i m i na te s o r r e d u c e s t h e g e n e r a t io n o r u s e o f h a z -
a r d o u s s u b s t a n c e s i n t h e d e s i g n , m a n u fa c t u r e , a n d
p y ra z o l o n e a n d i t s d e r i v a t i v e s a re h a v i n g n u m er o u s
m ed i c at i o n s . I t r ep re s en t s w i d e b i o l o g i c al a c t i o n s
3
i n cl u d i n g a n a l g e s i c, a n t i p y r e t i c , a n t i - i n fl a mm a t or y ,
1
4
a n t i o x i d a n t , a n t i b a ct er i a l , a n t i f u n g a l , a n t i c a n c er ,
5
6
a p p l i c at i o n o f c h e m i c a l p ro d u c t s ’’ . O n e o f t he p r i n ci -
7
p l e s o f g r e e n c h e m is tr y r e v e a l s t ha t s e l e c t i v e c at a l y t i c
r e a g e n t s a r e h i g he r t o s t o ic h i o m e t r i c r e a g e n t s i n
c h e m i c al s y n t h e s i s . I n r e c e nt y e a r s , t he m a g i c o f c at a l -
y s i s h a s p r o m p t e d s i g n i fi c a n t w a y s t o a c c e le r at e t h e
c o n v e r s i o n o f r e a c t a n ts i nt o a p p r o p ri a te p r o du ct s a n d
g i v e a v a r i e t y o f p h a r m a c e u t i c a l c o m p o u nd s . T h i s w i l l
r e d u c e t h e b u r d e n o f b y - pr od u c t a n d s a v e e n e r g y . T h e
u s a g e o f c a t a l y s t s i s f a v o u r e d b e c a us e i t g iv e s 1 0 0 %
a t om e c o n o m y. C a t a l y s t s a r e f u l l y r e c o v e re d w i t h o u t
a n y c h a n g e i n t h e i r c h e m ic a l a n d p h y s i c a l p ro p e rt i e s .
T h e c a t a l yz e d r e a c t io ns a r e f a s t e r, r e a c t io n y i e l d s a re
b e t t e r , a n d t h e r e i s m i n im a l p ro d u c t io n o f w a s t e m at er i al
a n d m a x i m u m u t i l i z a t i o n o f t he r e a c t a n t s . G r e e n s y n -
t h e s i s i s m ai n l y d e s i g n e d w i t h t h e i nt e n t io n t o p r o v i d e
c o m p ut at i on al e f fi c i e n c y i n m i n d , i n a d d i t i on , i t a l s o
c o n t r i b u t e s a n e w f o r m u la ti on b y m o le c u la r l e v e l t o
a ch i e v e s u s t a i n a b i l it y a n d m a te ri a ls s u i ta bl e f o r c o n -
v e n i e n c e . T h i s i s b o t h e f f e c t i v e a n d e f fi c ie n t , a n d
u r i c o s u r i c a n d a n t i t u b er c u l a r a ct i v i t i e s . V a r i o u s s y n -
t h et i c p y r a z o l o n e c o m p o u n d s h a v e p o t e n t i al c o r e a c t i v e
m o i e t y l i k e analgesic and antipyretic – a n t i p y r i n e ,
p r o p y p h e n a z o ne , anti-inflammatory – m et a m i z o l e ,
uricosuric – s u l fin p y r a zo n e ( Fi g u r e 1 ) .
B es i d e s , i t h a s b e e n o b s er v e d t h at s o m e s y n t h et i c
h e t e r o c y c l i c c o m p o u n d s w i t h a p y ra z o l o n e r i n g h a v e
a n t i o x i d an t a ct i v i t y .
T he co nd en sati on o f h yd ra zi ne h yd ra te a nd eth yla ce -
to ace tat e i s a re cog ni ze d w ay t o s ynt he si ze py ra zo lo ne
8
d er iv ati ve s. Me th an ol , e th an ol, d ime th yl fo rma mi de
9
1 0
1 1
a nd dio xan e c an be us ed as a so lv en t fo r t hi s tr an sf or -
mat io n. Co nse qu en tl y, th e r es ea rc h o f s ev er al su bs ti tu te d
p yr az ol on e d er iv ati ve s h as b een i nv es ti ga te d b y di ff er en t
met ho ds, us in g io ni c liq ui ds , es pe ci al ly ba se d o n th e
4,1 2
[H MI M]H SO
1 3
re us ab le c at aly st s, C uI n an op ar ti -
1 4
4 ,
c les , an d tu ng sto ph os ph oric a ci d. B esid es, a va ri ety
o f o th er c at al ys ts ar e al so u se d fo r t he s yn th es is o f th es e
* F o r c o r re s p o n d e n c e
Electronic supplementary material: The online version of this article (https://doi.org/10.1007/s12039-019-1679-5) contains supple-
mentary material, which is available to authorized users.

1 0 5 P a g e 2 o f 7
J. Chem. Sci.
( 2 0 1 9 ) 1 3 1 : 1 0 5
a n a l y s i s ( CH N ) a n d m el t i n g p o i n t s . I R s p e c t r a ( KB r
p e l l et ) w e r e r e co rd ed o n B ru k e r T e n s o r 2 7 F T - I R
s p e c t r o m e t e r a t S ri V e n k a t e s w a r a C o l l eg e o f P h a r m a c y ,
p yr az ol on e d eriv at iv es th ro ug h a c on den sa ti on re ac ti on .
In re ce nt ye ar s, a fe w c at aly sts h av e b ee n c omp ri se d a s
1 5
1 6
3 -a mi no pro py la te d s ili ca ge l, sil ic a s ul ph ur ic ac id ,
N -( 3- si lic ap ro pyl) -N -me th yl imid az oliu m hy dr og en
1
C h i t t o o r . H N M R s p e c t r a w e r e r ec o r d e d o n a B r u k e r
1 7
su lp hat e, so di um d od ec yl su lp hate , x ant ha n s ul fu ri c
1 8
D R X 4 0 0 s p e c t r o m e t e r a n d t h e e l e me n t al a n a l y s i s w as
p e r f o r m e d u s i n g a H e r a eu s C H N - O - R ap i d a n a l y z e r a t
S o p h i s t i ca t e d I n s t ru me n t at i o n F ac i l i t y , V I T U n i v e r s i t y ,
1 9
a cid , 1 ,3 -d is ul fo ni ca ci d imi da zo li um te tr ac hl or oa lu -
2 0
min at e, s ili ca -b on ded N -p ro py lp ip era zin e su lf ami c
2 1
a cid , a s r eu sa ble so li d ca ta ly st s. A lmo st al l th es e
V e l l o r e. N M R s p e c t r a w e r e r ec o r d e d i n C D C l a n d
3
D M SO -d6. C h e mi c a l s h i f t s (d) a re r e p o r t e d i n p p m
r e l a t i v e t o t e t r a m et h y l s i l a n e ( T M S ) a s a n i n t e r n a l
s t an d a rd . J v a l u es a r e g i v e n i n H z . H i g h - r es o l u t i o n
m as s s p e c t r o m e t r y ( H RM S ) s p e c t r a w e re r e co rd e d o n a
J E O L T M S- H X 1 1 0 m as s s p e c t r o m e t e r .
met ho ds h ad s ev er al limi ta tio ns s uc h a s mo re r ea cti on
ti mes , l es s p er ce ntag e yi el ds , t ire so me w or k- up p ro ce -
d ur es , us ag e of v ario us to xic so lv en ts a nd c atal ys ts .
T he re fo re , i t is ne ed ed t o ov erco me th es e di ffi cu lt ie s a nd
d ev el op a n ew w ay f or th e s yn th es is of py ra zo lo ne
d er iv ati ve s.
F r e e r a d i ca l s p l a y a v it a l r o l e i n h u m a n c el l p r o -
t e ct i o n a s i m m or ta l it y d e v e lo p m e n t a n d b r e a k t h r o u g h
o f d i s e a s e s . F r e e r a d i c a l s a l s o c a l le d a s r e a c t i v e o x y -
g e n s p e c i e s ( R O S ) , w h ic h c o nt a in h y d r o x y l r a d i c a l s
2 . 2 Synthesis
I n t h i s p r e s e n t w o r k , c o m p o u n d s w e r e s y n t h e s i z e d
a s s h o w n i n F i g u r e 2 . S u b s t i t u t e d 4 - b e n z y l i d e n e - 3 -
m e t h y l - 1 - ( 2 , 4 - d i n i t r o p h e n y l ) - 1 H - p y r a z o l - 5 ( 4 H ) - o n e
w e r e p r e p a r e d b y c o n d e n s a t i o n o f s u b s t i t u t e d b e n -
z a l d e h y d e , e t h y l a c e t o a c e t a t e a n d 2 , 4 - d i n i t r o -
p h e n y l h y d r a z i n e i n p r e s e n c e o f s i l i c a - s u p p o r t e d
z i n c c h l o r i d e ( S i O / Z n C l ) a s a r e c y c l a b l e c a t a l y s t
b y m u l t i c o m p o n e n t r e a c t i o n ( M C R ) . S u b s t i t u t e d
p y r a z o l o n e w a s p r e p a r e d b y t h e r e p o r t e d p r o c e -
d u r e . T h e m o s t i m p o r t a n t t a r g e t w a s t o d e v e l o p a n
e f f e c t i v e m u l t i - c o m p o n e n t a p p r o a c h f o r t h e s y n -
t h e s i s o f s u b s t i t u t e d 4 - b e n z y l i d e n e - 3 - m e t h y l - 1 -
-
-
( O H -) , s u p e r o x i d e a n i on s ( O ) , n i t r ic o x i de ( N O ) ,
2
h y d r o g e n p e r o x i d e ( H O ) a n d l ip i d p e r o x i d a t i o n . A s
2
2
a n t i o x i d a n t s c a n a c t a s a d e fe n c e m e c h a n is m a g a i n s t
e x p o s u r e t o f r e e d a m a g e c e l ls f u r th e r d e c i s i v e d u r i n g
t h e a i r p o l l u t i o n, s m ok e o f t ob a c c o , a l c o h o l s , p e s t i -
c i de s , d r u g a d d i c t io n , f ri e d g r o c e ri e s , a n d m a n y m o r e
2
2
2 2
c an e n h a n c e t h e r a d i c a l e x p o s u r e .
T h e p r e s e n t w o r k f o c u s e d o n d e v e lo p in g e f fi ci e n t
a n d g r e e n m et h o d s f or t he s y n t h e s is o f p h a r m a c o l o g -
i c al l y a c t i v e h e t e r oc yc li c c o m p o u nd s . N o w a d a y s ,
m u l t i - c o mp o n en t r e a c t io n s ( M C R s ) p l a y a v i t a l r o l e i n
t h e i m p r o v e m en t o f c o s t - e f fe c t i v e a n d e c o- f r i e n d l y
p r o t o co ls i n o r g a n i c s y n t h e s is i n a s i n g l e - s t e p r e a ct i o n .
I n p e r s i st en ce o f i nt e r e s t i n t he s y nt h e s i s o f h e t e r o -
c y c l i c c o mp o un ds, c o n s e q ue nt l y, t he s y n t h es i s o f
p y r a z o l o n e m o i e t y w a s p e rf o r m e d b y u s i ng a h e t e r o -
g e n e o u s c a t a l y s t i n w a t e r/ e th a n o l , i nc lu d i n g t h ei r
s p e c t r o s c o p y d a t a , a n d s t a ti s ti c a l a n a l y s i s o f t h ei r
a n t i o x i d a n t p o t en ti a l.
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t h r o u g h t h e r e a c t i o n o f v a r i o u s s u b s t i t u t e d a r o m a t i c
a l d e h y d e [ 1] w i t h 2 , 4 - d i n i t r o p h e n y l h y d r a z i n e [ 2]
a n d e t h y l a c e t o a c e t a t e [ 3] b y u s i n g s i l i c a - s u p p o r t e d
z i n c c h l o r i d e ( S i O / Z n C l ) a s a r e c y c l a b l e L e w i s
a c i d c a t a l y s t . A l l t h e r e a c t i o n s w e r e c a r r i e d o u t b y
r e fl u x i n g w i t h w a t e r / e t h a n o l a n d t h e y i e l d o f t h e
o b t a i n e d p r o d u c t s 4( a–f) w e r e g e n e r a t e d i n g o o d t o
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2. Experimental
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Propyphenazone
Antipyrine
A l l t h e c h e m i c al s a n d r e a g e n t s u s e d w e r e o b t a i n e d f r o m
A v r a , M e r c k a n d S i g m a - A ld ri c h C o . a n d w e r e u s e d
w i t h o u t a d d i t i o n a l p u r ifi c a ti on . M e l t i n g p o i n t s w e r e
d e t e r m i n ed i n o p e n c a p i l la r ie s i n E l i c o m e lt i n g p o i n t
a p p a r a t u s a n d w e r e u n c o r re c te d . T h e r e a c t io n s w e re
m o n i t o r ed b y t h i n l a y e r c h r o m a t o g r a p h y ( T L C ) u s i n g
s i l i c a g e l - G U V 2 5 4 p l a te s u s i n g 1 0 % a n d 2 0 % e t h y l
a ce t a t e a n d h e x a n e a s m o bi l e p h a s e . T h e fi n a l p r o d u c t s
w e r e c h a r a c t e r i z e d b y F o u r i e r -t r a ns fo r m i n f ra r e d ( FT -
O
H3C
CH3
O
N
N
N
O
S
O
N
HO
N
S
H3C
O
O
Metamizole
Sulfinpyrazone
Figure 1. I m p o r ta n t m a r k e t e d d r u g s c o n ta i n i ng p yr a-
z o l o n e r i n g .
1
I R ) , H n u c l e a r m a g n e t i c r e s o n a n c e ( N M R ), e l e me n t al

J. Chem. Sci.
( 2 0 1 9 ) 1 3 1 : 1 0 5
P a g e 3 o f 7
1 0 5
NO2
NO2
NHNH2
R
R
O
SiO2/ZnCl2
Catalyst
CHO
O
O
N
H3C
OC2H5
O2N
N
NO2
C2H5OH/ H2O,
60 oC
H
H3C
1
2
3
4(a-f)
Aldehyde
Products
Products
4d
Aldehyde
H3CO
H3CO
Cl
4a
H3C
H3C
N
4b
4e
H3C
N
CH3
4c
4f
OCH3
NO2
Figure 2. T h e s c h e m e f o r t h e s y n t h e si s o f p y r a z o l o n e d e r iv a t i v e s 4( a–f) .
e x c e l l e n t y i e l d s r a n g e d w i t h i n 8 6 – 9 4 % a n d r e s u l t s w a t e r ( 5 m L ) t h e r es u l t i n g m i x t u r e w a s e xt r ac t e d
a r e s u m m a r i z e d i n T a b l e S 1 , S u p p l e m e n t a r y w i t h e t h y l a ce t at e ( 3 91 0 m L ) . T h e c o m b i n e d
I n f o r m a t i o n . A s m e n t i o n e d i n T a b l e S 1 , d i f f e r e n t o r g a n i c l a y e r s w e re w a s h e d w i t h 1 0 % N a H C O a n d
3
a r y l a l d e h y d e s h a v i n g e l e c t r o n - w i t h d r a w i n g a n d w a t e r , d r i e d o v e r a n h y d r o u s N a S O a n d e v a p o r a t e d
2
4
e l e c t r o n - d o n a t i n g g r o u p s w e r e f o u n d t o g i v e u n d er r ed u c ed p r e s s u r e . T h e r es u l t i n g c r u d e p r o d u c t
f a v o u r a b l e c o m p o u n d s i n g o o d y i e l d s .
s u b s t i t u t e d 4-benzylidene-3-methyl-1-(2,4-dinitro-phe-
n y l ) - 1 H - p y r a z o l - 5 ( 4 H ) - o n e d e r i v a t i v e s w e r e p u r i fi e d b y
r e c r ys t a l l iz a t io n f r o m h o t e t h a n o l t o gi v e t h e d e si r e d
p r o d u c t s .
2 . 3 Preparation of catalyst (SiO2/ZnCl2)
T h e c a t a l ys t Z n C l s u p p o rt e d o n s i l i c a g e l w as p r e -
2
p a r e d a c co r d i n g t o t he p r e v i ou s p ro c e d u re . A b o u t 2 . 7
g o f Z n C l ( 1 2 m m o l ) w a s a d d e d t o 9 . 1 g s i l i c a g e l
2 . 5 Reusability of catalyst
2
( g r a d e 6 0 , 2 3 0 – 4 0 0 m e s h ) i n 5 0 m L e t h a n o l . 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 re d a n d r e fl u xe d f o r 1 h i n t h e
a b s e n c e o f l i g h t , fi l t e r e d , w a s he d w i t h d r y C C l a n d
T h e r e u s a b i l i t y o f t h e c at a l y s t w a s t e s t ed i n t h e s y n -
t h es i s o f 4 - b e n z y l i d e n e -3- me t h y l - 1 - ( 2 , 4 - d i n i t r o -p h e -
n y l ) -1 H - p y r a zo l - 5 (4 H ) - o n e . I n a t y p i c a l e x p e r i m e n t ,
a f t e r c o m p l e t i o n o f t h e r ea c t i o n , ( Si O / Z n Cl ) w as
4
2 3
d r i e d u n d e r v a c u u m a t 1 6 0 °C f o r 1 0 h .
2
2
i s o l a t e d f r o m t h e r e ac t i o n m i x t u r e b y fi l t r a t i o n a n d
w a s h e d w i t h e t h y l a ce t a t e a n d d r i e d o v e r a n h y d r o u s
N a S O . I f Z n C l i s u s e d a s a c at al y s t , i t l e a c h e s t h e
2 . 4 Synthesis of substituted 4-benzylidene-3-
methyl-1-(2,4-dinitrophenyl)-1H-pyrazol-5(4H)-
one using SiO2/ZnCl2 catalyst
2
2 ?
4
2
Z n i n t o t h e r e ac t i o n . T o m i n i mi ze t h e l e a c h i n g o f
z i n c i o n s , S i O w a s u s e d a s a s u p p o r t i n g a g e n t t o b i n d
2
A n e q u i m o l a r m i x tu re o f s u bs t it u t e d a r o m a t i c a l d e -
h y d e ( 0 . 0 2 m o l ) , e t h y l a c e t o a c e ta t e ( 0 . 0 2 m o l) a n d 2 , 4 -
d i n i t r o p he ny l hy dr a z i n e ( 0 . 0 2 m o l ) w e r e a d de d t o 0 . 1 0
g o f s u p p o r t ed Z n C l o n S i O ( 15 % , w / w ) i n 1 0 m L o f
w a t e r ( o r ) e t h a n o l i n r ou n d b o t to m fl a s k e q ui p p ed w i t h
c o n d e n se r a t 6 0 °C f or t h e g i v e n t im e ( T a b l e S 1 ,
S u p p l e m e n t ar y I n f or m a ti o n ) . A f te r c o m p le ti o n o f t h e
r e a c t i o n ( m o n i t o re d b y T L C ) , a n d d i l u t e d w i t h c o l d
t h e z i n c i o n s . H o w e v e r , n o s i g n i fic a n t l e a c h i n g o f t h e
m o d i fi e r w a s o b s er v e d u n d e r o u r r ea c t i o n c o n d i t i o n s .
I n t h e r ea c t i o n m i x t u r e, Z n c o n t en t w a s v e r i fi e d b y
a n a l y s i n g a ft e r fi l t e r i n g - o f f t h e c at al y s t . M o r eo v e r , n o
r ea c t i o n w a s o b s er v ed i n t h e s o l v e n t a ft e r r e m o v i n g
t h e c at a l y s t . U s i n g t h e r e cy cl ed c at al y s t f o r c o n s e cu -
t i v e t i me s i n t h e c h e mi ca l r e ac t i o n o f b e n z a l d e h y d e
a n d 2 , 4 -d i n i t r o p h e n y l- h y d r a z i n e f u r n i s h e d t h e p r o d u c t
2
2

1 0 5 P a g e 4 o f 7
J. Chem. Sci.
( K Br , c m -1 ) : 1 4 2 2 ( C = C
( 2 0 1 9 ) 1 3 1 : 1 0 5
) , 1 6 9 4 ( C = O ) , 1 3 3 2 ( N O ) ;
2
w i t h n o s i g n i fi c an t d e c r e a s e i n t he r e a c t io n y i e l d . T h e
r e c o v e r e d c a t a l ys t ( 98 % ) w a s r e u s e d t hr e e t i me s
w i t h o u t a n y l o s s o f a c t iv i ty . T h i s r e u s a b i li t y d e m o n -
s t r a t e s t h e h i gh s t a bi li t y o f t he c a t a l ys t u n d e r t h e
o p e r a t i n g c o n d i t i o n s .
a r o m at i c
1
H N M R ( 4 0 0 M H z , C D C l , d, p p m ) : 8 . 4 0 – 9 .7 3 ( m , 3 H ,
3
p h e n y l r i n g ) , 7 . 2 6 ( s , 1 H , - C = H ) , 6 . 7 1 – 7 .7 4 ( m , 4 H , p h e ny l
r i n g ) , 1 . 2 9 ( s , 3 H , - C H ) , 3 . 4 4 ( s , 6 H , 2 x N - C H ) ; A n al y t ic a l
3
3
c a l . C H N O : C , 5 7 . 7 2 ; H , 4 . 3 3 ; N , 1 7 . 7 1 ; F o un d: C ,
5 5
1 9 1 7
5 7 . 6 5 ; H , 4 . 3 8 ; N , 1 7 . 6 7 ; M S ( E I ) : ( m / z ) C a l c u l at e d f or
C H N O [ M?H ] ? : 3 9 5 . 1 2 3 0 ; F o u n d , 3 9 5 .3 6 8 8 ( R e l.
I n t. 1 0 0 % ) .
1 9 1 7
5 5
2 . 6 Spectral data of synthesized compounds
2 . 6 f Compound 4f: (4Z)-4-(2-nitrobenzylidene)-3-methyl-1-
(2,4-dinitrophenyl)-1H-pyrazol-5(4H)-one L i g h t y e ll o w
c r y s ta ll i n e s o l i d ; Y i e l d 8 8 % ; M . p . 2 1 2 °C ; F T - I R ( K B r ,
2 . 6 a Compound 4a: (4Z)-4-(3,4-dimethoxybenzylidene)-3-
methyl-1-(2,4-dinitrophenyl)-1H-pyrazol-5(4H)-one Y el-
2 3
l o w so l i d ; Y i e l d 9 2 % ; M . p . 2 1 8 °C ; F T - I R ( K B r , c m -1) : 1 1 82 ,
c m -1 ) : 1 6 0 8 ( C = C
) , 1 7 2 5 ( C = O ) , 1 4 9 5 , 1 3 3 1 ( N O ) ;
2
a r o m a t i c
1
) , 1 5 19 (C = N ) , 1 69 5 ( C = O ) , 13 4 2 ( N O ) ; H
1 41 2 ( C =C
1
a
r
o
m
a
t
i
c
2
H N M R ( 4 0 0 M H z , C D C l , d, p p m ) : 8 . 4 1 – 9 .1 0 ( m , 3 H ,
3
N M R (4 0 0 MH z, C D C l , d, p p m) : 8 . 0 1– 9 .0 3 ( d d, 3H , p h e n yl
3
p h e n y l r i n g ) , 7 . 2 7 ( s , 1 H , - C = H ) , 7 . 4 4 – 7 .6 6 ( m , 4 H , p h en yl
r i n g ) ; A n a l y t ic a l c a l . C H N O : C , 5 1 . 3 9 ; H , 2 . 7 9; N ,
1 7 . 6 3 ; F o u n d : C , 5 1 . 3 0 ; H , 2 . 8 2 ; N , 1 7 . 5 8 ; M S ( E I ) : ( m / z )
r i ng ) , 6 .9 5 ( s , 1H , - C =H ) , 6. 8 3– 7 .20 ( d d , 3H , p h en y l r i n g ) , 2 .2 9
( s , 3 H , - C H ) , 3 .8 7 ( s , 6 H , 2x - O C H ) ; A n al y ti c a l c a l .
1
7
1
1
5 7
3
3
C H N O : C , 5 5. 3 4 ; H , 3 . 91 ; N, 1 3. 5 9. F o un d : C , 5 5 .3 1 ; H ,
1 9 1 6 4 7
C a l c u l a t e d f o r C H N O [ M ?H ] ?: 3 9 7 .2 9 8 5 ; F o u nd ,
3 9 7 .0 6 5 8 ( R e l . I n t. 1 0 0 % ) .
1 7 1 1
5 7
3 .9 3 ; N , 13 . 60 ; M S ( E I ) : ( m / z ) C a l c u l a t ed fo r C H N O
4 7
1 9 1 6
[ M ?H ] ? : 4 1 2 .3 5 29 ; F o un d , 4 1 2 .0 6 32 (R e l . I n t . 10 0 % ).
2 . 6 b Compound 4b: (4Z)-4-(4-(dimethylamino)benzyli-
dene)-3-methyl-1-(2,4-dinitro-phenyl)-1H-pyrazol-5(4H)-
2 . 7 Evaluation of in-vitro antioxidant activity
2 3
one O r an g e c r y s ta l l i n e s o l i d ; Y i e l d 9 4 % ; M . p . 2 3 6 °C ;
) , 1 6 2 8 ( C = N ) , 1 7 1 3
a r o m a t i c
F T - I R ( K Br , c m -1) : 1 4 1 7 ( C = C
T he ac tiv it y o f th e s yn th es iz ed co mpo und s w as qu an ti -
ta ti ve ly me asu re d b y d ip he ny lp ic ry lh yd ra zy l ( DPP H)
2 5
ra dica l a ss ay met ho d to ch ar ac te riz e an tio xid an ts .
1
( C = O ) , 1 3 0 6 ( N O ) ; H N M R ( 4 0 0 M H z , C D C l , d, p p m ) :
2
3
8 . 4 0 – 9 . 03 ( d d , 4 H , p h e n y l r i n g ) , 8 . 0 1 ( d , 1 H , - C = H ) ,
6 . 8 0 – 6 . 83 ( d d , 3 H , p h e n y l r i n g ) , 2 . 9 4 ( s , 3 H , - C H ) , 2 . 2 9 ( s ,
3
Wh en a nt iox id ant s r ea ct w ith s ta bl e f re e r ad ic al (D PP H) ,
it ge ts co nv erte d int o 1 ,1 -d ip hen yl -2 -p ic ry l h yd ra zi ne .
T he s ta bl e f re e ra di ca l D PPH wa s mea su re d by a d ec re as e
i n a b so rb an c e a t k 54 0 n m, w hi ch is p ur pl e in co lo ur .
A sc or bi c ac id w as us ed a s th e st an dar d dr ug . Th e p er c en t
sc ave ng in g ac ti vi ty w as ca lc ula te d b y us in g th e fo rmu la ,
6 H , 2 x C H ) ; A n a ly t i c a l c a l . C H N O : C , 5 7 . 7 2 ; H , 4 . 3 3 ;
3
1
9
1
7
5
5
N , 1 7 . 7 1 ; F o u n d : C , 5 7 . 6 8 ; H , 4 . 3 7 ; N , 1 7 . 6 5 ; M S ( E I ) : ( m /
z ) C al c u l at e d f o r C H N O [ M ?H ] ? : 3 9 6 . 1 2 6 3 ; F o u n d ,
3 9 6 . 1 2 3 6 ( R e l. I n t . 1 0 0 % ) .
1 9 1 7
5 5
2 . 6 c Compound 4c: (4Z)-4-(2-methoxybenzylidene)-3-
methyl-1-(2,4-dinitrophenyl)-1H-pyrazol-5(4H)-one L i g h t
2 4
y e l l o w c r y s t al l i n e s o l i d ; Y i e l d 9 1 % ; M . p . 2 2 8 °C ; F T - I R
) , 1 7 0 1 ( C = O ) , 1 5 6 1 ( C = N ) ,
a r o m a t i c
Control À Test
( KB r , c m -1 ) : 1 4 1 8 ( C = C
S ca v e n g i n g a ct i v i t y ð%Þ ¼
 1 0 0
1
Control
1 5 0 6 , 1 3 2 5 ( N O ) ; H N M R ( 4 0 0 M H z , C D C l , d, p p m ) :
2
3
8 . 2 1 – 9 . 03 ( d d , 3 H , p h e n y l r i n g ) , 8 . 0 3 ( d , 1 H , - C = H ) ,
7 . 1 0 – 7 . 41 ( d d , 4 H , p h e n y l r i n g ) , 2 . 2 9 ( d , 3 H , - C H ) , 3 . 8 4 ( s ,
DPPH method T h e s t o c k s o l u t io n w a s p r e p a r e d b y u s i n g
D P P H ( 1 0 m g ) d i s s o l v e d i n 1 0 m L d i m e t h y l s u l fo x id e
( D M S O ) a n d a d d e d a t v a r io u s c o n c e n t r a t i o n s i n e t h an ol i c
s o l u t i o n ( 1 0 m L ) . S o l u t io n s o f t h e t e s t c o m p o u n d s i n v ar i -
o u s c o n c e n t r a t i o n s ( 1 2 5 , 2 5 0 , 5 0 0 lg / m L ) a s w e l l a s o f
a s c o r b i c a c i d a s r e f e r e n c e s t a n d a r d w a s p r e p a r e d i n e th a no l .
A n a l i q u o t o f e a c h o f t h e s e s o l u t i o n s ( 1 .0 m L ) w a s t ak e n i n
d i f f e r e n t 1 0 m L v o l u m e t r i c fl a s k s t o w h i c h t h e D P P H s t o c k
s o l u t i o n ( 1 .0 m L ) w a s a d d e d a n d v o l u m e w a s m a d e t o 1 0
m L . T h e p l a t e s w e r e i n c u b a t e d a t 3 7 °C f o r 2 0 m i n a nd t he
a b s o r b a n c e o f e a c h s o l u t io n w a s m e a s u r e d a t 5 4 0 n m a nd
3
3 H , - O CH ) ; A n a l y t i c a l c a l . C H N O : C , 5 6 . 5 5 ; H ,
1 8 1 4 4 6
3
3 . 6 9 ; N , 1 4 . 6 5 ; F o u n d : C , 5 6 . 6 8 ; H , 3 . 6 7 ; N , 1 4 . 6 0 ; M S
( E I ) : ( m / z) C al c u l a t e d f o r C H N O [ M ?H ] ?
3 8 2 . 0 9 1 3 ; F o u n d , 3 8 2 . 1 6 8 2 ( R e l . I n t . 1 0 0 % ).
:
1 8 1 4
4 6
2 . 6 d Compound 4d: (4Z)-4-(4-chlorobenzylidene)-3-methyl-
1-(2,4-dinitrophenyl)-1H-pyrazol-5(4H)-one O r a n g e
c r y s t al l i n e s o l id ; Y i e l d 8 6 % ; M . p . 1 7 8 °C ; F T - I R ( K Br ,
c m -1 ) : 1 1 2 7 , 1 4 2 4 ( C = C
) , 1 7 4 1 ( C = O ) , 1 5 1 2 ( C = N ) ,
a r o m a t i c
1
1 3 2 0 ( N O ) ; H N M R ( 4 0 0 M H z , C D C l , d, p p m ) :
2
3
2 6 – 2 8
p e r f o r m e d i n t r i p l ic a t e .
8 . 0 3 – 9 . 03 ( d d , 3 H , p h e n y l r i n g ) , 8 . 1 0 ( m , 1 H , - C = H ) ,
6 . 8 2 – 7 . 45 ( m , 4 H , p h e n y l r i n g ) , 2 . 2 9 ( s , 3 H , - C H ) ; A n a -
3
l y ti c al c al . C H N O C l : C , 5 2 . 7 9 ; H , 2 . 8 7 ; N , 1 4 . 4 9 ;
1 7 1 1
4
5
3. Results and Discussion
F o u n d : C , 5 2 . 6 8 ; H , 2 . 8 2 ; N , 1 4 . 5 3 ; M S ( E I) : ( m / z ) C a l -
c u l a t e d f o r C H C l N O [ M?H ] ? : 3 8 6 . 0 4 1 8 ; F o u n d ,
3 8 6 . 1 7 4 6 ( R e l. I n t . 1 0 0 % ) .
1
7
1
1
4
5
3 . 1 Spectral data and interpretation
of the compounds
2 . 6 e Compound 4e: (4Z)-4-(3-(dimethylamino)benzylidene)-
3-methyl-1-(2,4-dinitro-phenyl)-1H-pyrazol-5(4H)-one
O r a n g e c r y s t al l i n e s o l i d ; Y i e l d 9 0 % ; M . p . 2 3 0 °C ; F T - I R
1
T h e p r o d u c t s w e re i d en t i fi e d b y I R, H N M R s p e c-
1
t r o s co p y a n d e l e me n t al a n a l y s i s . I n H N M R s p e c t r u m

J. Chem. Sci.
(
2
0
1
9
)
1
3
1
:
1
0
5
P
a
g
e
5
o
f
7
1 0 5
o f 4( a–f) i t r e v e a l e d a m u l ti p le t f o r t h e t w o a r o m a t i c f r ee c o n d i t i o n s , w h e r e, i n i t i al l y a t r a c e a mo u n t o f
h y d ro ge n’ s r a n g e a t d 8 . 41 – 9 . 7 9 p p m a n d d 6 . 6 9 – 7 . 7 4 p r o d u c t h a d f o r me d ( T a b l e S 2 , e n t r y 1 , S u p p l e m e n t a ry
p p m . O n e s i n g l e t r e l a t e d t o t h e e t h yl e n e h y d r o g en a t d I n f o r m at i o n ) , s i g n i f y i n g t h e n e e d o f a c at a l y s t . T o
7 . 1 2 –7 . 3 8 p p m a n d o n e s i n gl e t r e l a t e d t o t h re e e n h a n c e t h e y i el d o f t h e p r o d u c t a n d t o o p t i m i z e t h e
h
y
d
r
o
g
e
n
’
s
o
f
–
C
H
g
r
o
u
p
a
t
d
1
.
2
2
–
1
.
2
9
p
p
m
.
r ea c t i o n c o n d i t i o n s , i t w a s t h en s t u d i e d i n t h e p r e se n c e
o f d i ff e r en t c at al y s t s s u c h a s A l C l , Z n C l , F e Cl ,
S i O - Cl , S i O / Z n Cl . M a x i mu m y i el d ( 8 6 % ) w as
3
3
2
3
3 . 1 a Characterization of Catalyst (SiO2/ZnCl2): T h e
F T - I R s p e c t r u m o f t he c a t a l ys t ( S i O / Z n C l ) i s s h o w n
2
2
2
2
2
o b t a i n e d w h e n t h e r e ac t i o n w a s c ar r i e d o u t w i t h
1 0 m o l % o f t h e S i O / Z n Cl c at al y s t .
i n F i g u r e S 1 , S u p pl e m e n t a ry I n f o r m a t i o n . T h e F T - IR
s p e c t r u m o f t h e c a t a l yt ic s y s t e m d i s p l a y e d a
s y m m e t r i ca l s t r e t c h in g b a n d a t 3 4 3 4 c m-1 f o r
h y d r o x y l g r o u p a n d t he b a nd r e s o n a ti n g a t 1 6 1 0
c m-1 w a s a t t r i bu t e d t o t he b e n d i n g o f a d s o r b e d w a t e r .
A b a n d a p p e a r e d a t 1 1 7 2 c m-1 a n d t hi s c an b e
a t tr i b ut e d t o t h e b e nd i ng o f S i - O -S i a n t is y m me t ri c
s t r e t c h i n g v i b r a t i o n s a n d t h e b a nd a t 8 1 7 c m -1 w a s
a l so e v i d e n c e o f t he s y m m e tr i c s t r e t c h in g v i b r at i o n o f
t h e r o c k i n g m o de o f S i - O -S i. T h e O - H s t r e t c h i n g b a n d
a r o u n d 3 4 3 4 c m -1 w a s a l s o p re s e n t e d i n t he c at al y s t .
C o n si d e r i n g t h e F T -I R s p e c t ra o f S i O / Z n C l , i t w a s
2
2
O u r a n a l y s i s r e v e al ed t h at t h e o p t i m u m a m o u n t o f
S i O / Z n Cl w a s r el a t i v e t o t h e r ea c t a n t . T h e c a t a l y s t
2
2
p l ay s a c ru ci al r o l e i n t h e r e ac t i o n . T h e r e s ul t s a r e
s u m m ar i z e d i n T a b l e S 2 , S u p p l em e n t ar y I n f o r m a t i o n .
T h e r ea c t i o n i m p r o v e d w i t h a l m o s t t h e s a m e e a se w i t h
a r o ma t i c a n d a l i p h a t i c a l d e h y d es . V a r i o u s f u n c t i o n al
g r o u p s s u c h a s m et h o x y ( O CH ) , d i me t h y l a m i no
3
( N ( CH ) ) , c h l o ro ( Cl ) a n d n i t r o ( N O ) g r o u p s c o n -
3 2
2
t a i n i n g c o m p o u n d s w e re t o l e r at ed . H o w e v e r , t h e r e a r e
n o s i g n i fic a n t c h a n g e s i n t h e y i el d t h at w e re o b s e r v e d
w h e n m o r e t h an o n e s u b s t i t u t e w a s p r e s e n t i n t h e
p h e n y l r i n g ( T a b l e S 1 , e n t r y 1 ) . H e n c e, e l e ct r on i c a n d
s t er i c f a ct o r s p l ay ed a n e g l i g i b l e r o l e i n t h i s p r o t o c o l .
2
2
c o n c l u d e d t h a t Z n C l w a s s u c c e s s f u l l y c o a t e d w i t h
2
2
9
s
i
l
i
c
a
l
a
y
e
r
.
3
.
2
O
p
t
i
m
i
z
a
t
i
o
n
s
t
u
d
i
e
s
3 . 3 A tentative mechanistic pathway
for the multicomponent reaction
I n t h e p r e s e n t s t u d y , i n t h e fi r s t s e ri e s o f e x p e r i m en t s ,
a n i n v es t i ga t i o n w a s d o n e o n t h e e f f e c t o f c at al y s t
l o a di n g , t h e n a t u re o f s o l v e n t , o p t im u m r e ac t i o n
t e m p e r a t u r e a n d t he t im e t a k e n . I n i t ia ll y , t he t h re e -
c o mp o ne nt r e a c t i o n w a s c o nd u c te d o n 2 m m o l s c a l e o f
b e n z a l d e h y d e , 2 , 4 -d in i tr o p h e n y l h y dr a z i n e a n d e t h y l
a ce t o a c et a t e a t a s u i ta b l e t e m p e r a t u re , u n d e r c at a l y s t -
T he p la us ib le mec han is m fo r th e sy nt he si s o f su bs ti -
tu te d
4
-
b
e
n
z
y
l
i
d
e
n
e
-
3
-
m
e
t
h
y
l
-
1
-
(
2
,
4
-
d
i
n
i
t
r
o
p
h
e
n
y
l
)
-
1 H- py ra zol- 5(4 H) -o ne ha s b een sh ow n in F ig ure 3. T he
fi rs t st ep in vo lv es th e c on de nsa tio n o f 2 ,4 -d in it ro -
p he ny lh yd ra zin e w it h e th ylac etoa ceta te fo r th e
H3C
H3C
NO2
H
OH
O
N
N
N
O
N
H
O
N
NH2
O2N
H3C
OC2H5
O2N
O2N
-C2H5OH
1
3
NO2
Ar
NO2
2
Ar
H
Zn
H3C
H3C
H
2
O
H3C
Ar
N
N
OH
O
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r
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t
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v
i
t
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A l l t h e s y n t h e s i z e d c o m p ou n d s w e r e s u b j e c t e d t o
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s c av en gi n g a s s a y m e th o d a n d d u e t o t he ir h y d r o g e n
d o n a t i n g a b i l i t y . A s m e nt i on e d i n T a bl e S 3 ( Su p p l e-
m e n t a r y I n f o r m a t i o n ) , s i x c o m p o u nd s 4(a–f) s h o w ed
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d a t a t h a t t h e s c a v e n g i n g a c t iv it y o rd e r o f t h e t e s t
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2
6 . E l - G a b y M S A , G h o r a b M M , I s m a i l Z H , A b de l -
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d e r i v a ti v e s Med. Chem. Res. 27 7 2
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3
7 . A l - M u ta ir i A A , E l - B a i h F E M a n d A l - H a z i m H M
2 0 1 0 M i c r o w a v e v e r s u s u l t r a s o u n d a s s i s t e d s y n t h es i s o f
s o m e n e w h e t e r o c y c l e s b a s e d o n p y r a z o l o n e m o ie t y J.
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8 . P a l S , M a r e d d y J a n d D e v i N S 2 0 0 8 H i g h s p e ed
s y n t h e s i s o f p y r a z o l o n e s u s i n g m i c r o w a v e - a s s i s t ed n ea t
r e a c t io n t e c h n o lo g y J. Braz. Chem. Soc. 19 1 2 0 7
9 . M o u s a S A S , I s h a k E A , B a k h e e t M E M a n d S h a na b F
A 2 0 1 5 A n e w r o u te f o r t h e s y n t h e s i s o f p y r a z o lo n e
d e r i v a ti v e s Elixir Org. Chem. 89 3 6 8 5 4
1 0 . G u p ta P a n d G u p ta J K 2 0 1 6 S y n t h e s i s a n d I n- v it r o
a n t i f u n g a l e v a l u a t i o n o f 5 - p y r a z o l o n e s Open Chem. J.
3 1 7
1 1 . G u n k a r a O T , B a g d a t l i E a n d O c a l N 2 0 1 3 S y n t h e s i s o f
n e w p y r a z o l o n e d y e s J. Chem. Res. 37 2 2 7
1 2 . Z a n g H , S u Q , G u o S , M o Y a n d C h e n g B 2 0 11 A n
e f fi c i e n t o n e - p o t s y n t h e s i s o f p y r a z o l o n e d e r i va t i ve s
p r o m o t e d b y a c i d i c i o n i c l iq u i d Chin. J. Chem. 29 2 20 2
1 3 . Z i a r a t i A , G h o m i J S a n d R o h a n i S 2 0 1 3 S o n oc h e m i -
c a l l y s y n t h e s i s o f p y r a z o l o n e s u s i n g r e u s a b l e c at a l y s t
C u I n a n o p a r t i c l e s t h a t w a s p r e p a r e d b y s o n i c a ti o n Ul-
trason. Sonochem. 20 1 0 6 9
1 4 . M i n Z L a n d H u X M 2 0 1 3 T u n g s to p h o s p h o ri c A c i d-
C a t a ly z e d S y n t h e s i s o f P y r a z o l o n e s i n W a t e r Asian J.
Chem. 25 7 2 9 0
1 5 . S o b h a n i S , H a s a n i n e j a d A , M a l e k i M F a n d P a r i zi Z
P 2 0 1 2 T a n d e m K n o e v e n a g e l – M i c h a e l r e a c t i on o f
1 - p h e n y l- 3 - m e t h y l- 5 - p y r a z o l o n e w i t h a l d e h y d e s u s i n g
3 - a m in o p r o p y l a t e d s i li c a g e l a s a n e f fi c i e n t a nd r eu -
s a b l e h e t e r o g e n eo u s c a t a l y s t Synth. Commun. 42
2 2 4 5
1 6 . N i k n a m K a n d M i r z a e e S 2 0 1 1 S i li c a s u l f u r i c a ci d , a n
e f fi c i e n t a n d r e c y c l a b l e s o l i d a c i d c a t a l y s t f or t he
s y n t h e si s o f 4 , 4 0- ( a r y lm e t h y le n e ) b is ( 1 H - p y r a z o l - 5- o ls )
Synth. Commun. 41 2 4 0 3
4. Conclusions
I n s u m m a r y , a s i m p l e , m i n i m i z i n g b y - pr od u c t s , m ax -
i m i zi n g a t o m e c o n om y a n d e c o- fr i e n dl y s y n t h es i s o f
s u b s t i t u t e d p y r a z o lo n e s u s i n g S i O / Z n C l a s a r ec y -
2
2
c l ab l e h e t e r o ge ne o u s c a t a l y s t w a s f o r m e d . T h e s y n -
t h e s i z e d c o mp o un ds w e r e a c k n ow le d g e d b y s p e c t r a l
d a t a a n d c o mp o un d s t ha t i ll u s t ra t e d s i g ni fi ca n t t o
m o d e r a t e a c t i v i t y f or in vitro a n t io x i d a n t a c t iv i t y . T h e
m o s t i m p o r t a nt o n e o f t h i s m e th o d o lo g y i s t he u s e o f
m i l d r e a c t i o n c o n d i ti o n s , s h or t e r r e a c t io n t im e s a n d
h i g h e r y i e l d s . T h e p r o du c t s w e r e o b t a i ne d w i th a h i g h
y i e l d o f 8 6 – 9 4 % t hr ou g h m u l ti -c o m p o n e n t r ea c t i o n
a n d m a y p o s s i b l y b e u s e d i n t he s y nt h e s i s o f v a r i o u s
b i o l o g i c a l l y a c t i v e c o m p o u nd s . T h e s e c a t a l y s t s a re
f u l l y r e c o v e r e d f o r t hr e e c o n s e c u t i v e r un s w i t h o u t a n y
c h a n g e i n t h ei r c a t a l y ti c a c t iv i ty .
Supplementary Information (SI)
1
C h a r ac t er i za t i o n d a t a a n d c o p i e s o f H N M R s p e c t r a o f
c o m p o u n d s a r e r e p o r t e d a n d a v a i l a b l e a t w ww . i a s . a c . i n /
c h e m s ci .
Acknowledgements
T h e a u th o r s t h an k t h e M a n a g e m e n t a n d t h e P ri n c i p a l o f S r i
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t h e f a ci l i t ie s a nd fi n a n c i a l a s s i s t a n c e t o c a rr y o u t t h i s s t u d y .
T h e y a r e a ls o t h an k f u l t o S IF , V IT U n i v e r s i t y , V el l o r e f o r
t h e s p ec t r a l a na l y s i s .

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