Di

sser
tat
ion2018-
19

M.Sc.Di
sser
tat
ionent
it
led

“
Mul
ti
componentSy
nthesi
sofSul
fonami
de-
Thi
azol
i
dinoneHy
bri
ds”

Submitt
edby: Submi t
tedt
o:
PankajKumarChat
urv
edi Depart
mentofChemist
ry
Superv
isor
:Prof
.K.
N.Singh I
nsti
tut
eofScience,
BHU

1
 Di
sser
tat
ion2018-
19

ACKNOWLEDGEMENT

Myf
ir
standf
oremostsenseofpr
ofoundobl
i
gat
ionandhear
tfel
tgr
ati
tudet
omy
r
espect
ed t
eacherand super
visorPr
of.K.N.Si
ngh,Depar
tmentofchemi
str
y,
Banar
as Hi
ndu Uni
ver
sit
yforhi
s encour
agement
,di
scussi
on and a sy
stemat
ic
appr
oach t
othe subj
ect
.Thr
ough hi
sinsi
ght
s,r
esear
ch st
eeped i
ntel
l
ectand
del
egat
ion;hehasal
way
sal
armedandmadeapat
honwhi
chIhav
efol
l
owedmy
j
our
neyofl
ear
ningandexpr
essi
on.

Iam t
hankf oPr
ult of.D.S.Pandey
,HeadofDepar
tment
,andal
lthef
acul
tymember
s
f
oror
gani
zi
ngsuchv
aluabl
edi
sser
tat
ionpr
ogr
am f
orus.

Iam gr
atef
ulf
rom t
hecor
eofmyhear
ttoev
eryper
sonr
elat
edt
othepr
oject
.I
si
ncer
ely acknowl
edge t
he af
fect
ion, encour
agement
, gui
dance and usef
ul
suggest
ionsIr
ecei
vedf
rom Dr
.Pr
eet
idur
ingmypr
ojectwor
k.Iwoul
dal
sol
i
ket
o
hankMr
t .RahulSi
ngh,Mr
.Saur
abhKumar
,Mr
.AnupkumarShar
ma,Mr
.Ramesh
Vi
shwakar
ma,Mr
.AnandPandey
,Mr
.Shi
vChandr
aVer
ma,Mi
ss.Anj
aliandMr
.
Pr
incef
ort
hei
rcont
inuoushel
pandcr
it
ical
suggest
ionst
hroughoutt
hepr
oject
.Iam
al
sot
hankf
ult
omyl eMi
abmat ss.Adi
sht
aandmycol
l
eagues,wi
thoutwhom i
n
absencenot
hingcoul
dbepossi
ble.

Mysi
ncer
ethankst
oDepar
tmentofChemi
str
y,B.
H.U.f
orpr
ovi
dingf
aci
l
iti
esi
nthe
depar
tmentandt
her
espect
ivel
ab.

Lastbutnott
hel
eastIwoul
dli
ket
osayspeci
alt
hankst
omypar
ent
s,Iwi
l
lal
way
s
r
emembert
hemant
raofpat
ienceandper
sev
erancet
hatt
heyt
aughtandgav
ethe
st
rengt
handt
hecour
aget
oenabl
emet
owi
thst
andt
hehar
dti
medur
ingt
hewor
k.

May
,2019 Pankaj
KumarChat
urv
edi

2
 Di
sser
tat
ion2018-
19

CERTI
FICATE

Thi
sist
o cer
ti
fi
ed t
hatMr
.PankajKumarChat
urv
edi(
Exami
nat
ion Rol
lNo.
17419CHE054 &enr
oll
mentno.399628)
,ast
udentofM.
Sc.f
inaly
earwi
thOr
gani
c
Chemi
str
yspeci
ali
zat
ioni
ntheDepar
tmentofChemi
str
y,B.
H.U.Var
anasi
,wor
kedf
or
hi
sdi
sser
tat
ionundermysuper
visi
on,ont
het c“
opi Mul
ti
componentSy
nthesi
sof
Sul
fonami
de-
Thi
azol
i
dinoneHy
bri
ds”dur
ing4thsemest
er.

Thewor
kincl
udedi
nthi
spr
ojectr
epor
twasdonebyhi
m sat
isf
act
ori
l
yint
hegi
ven
t
imeper
iod.

May
,2019 Headoft heDepar tment Prof.K.N.Singh
DepartmentofChemi str
y Depart
mentofChemi st
ry
Insti
tut
eofSci ence Insti
tuteofScience
BanarasHinduUni ver
sit
y BanarasHi nduUniver
sit
y
Varanasi
-221005 Varanasi-
221005

3
 Di
sser
tat
ion2018-
19

TABLEOFCONTENTS

1.I
ntr
oduct
ion 05-
10

2.Exper
iment
alSect
ion 10-
13

3.Concl
usi
on 13-
13

4.Spect
ral
Dat
a 14-
17

5.Ref
erences 18-
19

6.Spect
ra 20-
24

4
 Di
sser
tat
ion2018-
19

I
NTRODUCTI
ON

Mul
ti
componentReact
ions:

Gr
eenchemi
str
ypr
imar
il
yfocusesont
hei
nnov
ati
vedesi
gnofchemi
calpr
oduct
s

andpr
ocessest
omi
nimi
zet
heuseandgener
ati
onofsubst
anceshazar
doust
othe
1-
2
env
ironmentandhumanheal
th. Fr
om t
hisper
spect
ive,mul
ti
componentr
eact
ions

(
MCRs)hav
eat
tai
nedconsi
der
abl
epr
omi
nenceduet
othei
rhugegr
eencr
edent
ial
s.

MCRsenabl
efastpr
oduct
ionofsuchhet
erocy
clesi
nsi
ngl
eoper
ati
onwi
thadequat
e

chemi
caldi
ver
sit
yfr
om r
eadi
l
yaccessi
bler
eagent
sandt
husadmi
ret
hedemandi
ng
3-
5
eco-
compat
ibi
l
itycr
it
eri
ali
kest
ep-andat
om economy
. MCRsar
ebr
oadl
ydef
ined

as“
one-
pot
”pr
ocesses t
hatengageatl
eastt
hreecomponent
ssi
mul
taneousl
y(so

cal
l
ed“
tandem”
,“domi
no”or“
cascade”r
eact
ions)andl
eadt
othepr
oduct
sthat

i
deal
l
yincor
por
ate al
lat
oms oft
he st
art
ing mat
eri
als.I
n addi
ti
on,t
hey of
fer

adv
ant
agesl
i
keoper
ati
onalsi
mpl
i
cit
y,f
aci
l
eaut
omat
ion,mi
nimalwast
egener
ati
on

andhi
gherpr
oducty
iel
ds,
ther
ebyr
educi
ngt
hecost
,ti
meandener
gy.Consequent
ly,

MCRshav
ebeenest
abl
i
shedasapower
fult
ooli
ncombi
nat
ori
alchemi
str
yast
hey

ar
efaci
l
e,ef
fi
ci
ent
,at
om economi
candamenabl
etoaut
omat
ion.Duet
othese

r
emar
kabl
e adv
ant
ages,t
he desi
gn ofnov
elMCRs wi
th gr
een cr
edent
ial
s has
6-
8
becomeadi
scer
nibl
ethemeofcur
rentor
gani
csy
nthesi
sanddr
ugdi
scov
ery
.

Hy
bri
dmol
ecul
es:

Hy
bri
dmol
ecul
eshav
erecent
lyat
tract
edagr
eatdealofat
tent
ioni
nthear
eaofdr
ug
9-
10
di
scov
eryanddev
elopment
. Thegoalofdev
elopi
ngsuchhy
bri
ddr
ugsi
stocr
eat
e

anewt
her
apeut
icent
it
ythati
sabl
etomodul
atebi
ologi
calpr
ocesseswi
thmul
ti
ple

orcombi
nedact
ivi
ti
es.Forexampl
e,Car
vacr
olI
,anat
ural
l
yoccur
ri
ngmonot
erpenoi
d

5
 Di
sser
tat
ion2018-
19

exhi
bitpot
entant
i-
fungalpr
oper
ti
eswhi
l
ebenzoy
lpheny
lur
eader
ivat
iveI
Iisan

i
nsect
ici
de whi
ch i
nhi
bit
s chi
ti
n sy
nthesi
s.I
nter
est
ingl
y,Pet
e etal
.in 2012

sy
nthesi
zedt
hei
rhy
bri
dsI
IIwhi
chexhi
bit
edpot
entant
i-
fungalact
ivi
ti
esagai
nst
9
candi
daal
bicansal
ongwi
thgoodi
nsect
ici
dal
proper
ti
es(
Fig.1)
.

Fi
gur
e1.Bi
ologi
cal
l
yact
ivehy
bri
dmol
ecul
es.

Among N,
S-cont
aini
ng mol
ecul
es, sul
fonami
de and t
hiazol
i
dinone ar
e t
wo
11-
15
‘
‘
pri
vi
leged’
’ scaf
fol
ds empl
oyed i
n dr
ugs and phar
maceut
ical
s. Some

r
epr
esent
ati
veexampl
esofsuchscaf
fol
dsar
eshowni
nFi
g.1,
whi
chexhi
bitabr
oad

spect
rum ofbi
ologi
calact
ivi
tyi
ncl
udi
ngant
icancer
,ant
i-
micr
obi
al,
ant
i-
diabet
ic,
ant
i-
11-
15
i
nfl
ammat
ory
,et
c. Thus,a hy
bri
d mol
ecul
e cont
aini
ng sul
fonami
de and

t
hiazol
i
dinonef
ramewor
ks(
Fig.2)i
sbel
i
evedt
obeexi
gent
,andt
hesy
nthesi
sof

suchmol
ecul
esunderenv
ironment
all
ybeni
gncondi
ti
onsi
swor
thi
nvest
igat
ing.

6
 Di
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tat
ion2018-
19

Fi
gur
e2.Sul
fonami
de/
thi
azol
i
dinescaf
fol
dsandt
hedesi
gnedmol
ecul
e.

Sur
veyofexi
sti
ngl
i
ter
atur
e:

Thephar
macol
ogi
calr
ecor
dsoft
hesepr
ivi
l
egedmot
if
sencour
aget
hesy
nthesi
sof

Sul
fonami
de-
Thi
azol
i
dinonehy
bri
ds.Sur
pri
singl
y,t
o dat
e,t
her
ear
eno l
i
ter
atur
e

pr
ecedent
sforsy
nthesi
soft
hei
rSul
fonami
de-
Thi
azol
i
dinonehy
bri
ds. Howev
er,

sy
nthet
icpat
ter
nsofi
ndi
vdualN,
i N’-
subst
it
utedt
hiour
eaandt
hiazol
i
dinonecor
es

ar
e wel
ldocument
ed.Fi
rst
,Sar
tor
iand cowor
ker
srepor
ted t
he sy
nthesi
s of

sy
mmet
rcalN,
i N’-
disubst
it
utedt
hiour
easf
rom ami
nesandCS2 usi
ngZnO/
Al2O3 as

het
erogeneousand r
eusabl
ecat
aly
st.Second,Schenone etal
.dev
eloped t
hese

der
ivat
ives i
n anhy
drous THF usi
ng sul
fony
lhy
drazi
de and i
sot
hiocy
anat
e as
15-
16
r
eact
ingpar
tner
s(Scheme1)
.

7
 Di
sser
tat
ion2018-
19

Scheme1.Li
ter
atur
erepor
tforsy
nthesi
sofN,
N’-
disubst
it
utedt
hiour
eas.

Ont
heot
herhand,Soharandhi
sgr
oupdev
elopedt
hiazol
i
dinonecor
ebyanaci
d

medi
atedt
wost
epr
eact
ionbet
weenacet
ylf
err
oceneandt
hiosemi
car
bazi
de,and,
17
al
bei
tthedesi
redpr
oducti
n28%y
iel
d(Scheme2)
. Lat Hassanetal
eron, .in2011

r
epor
tedt
hesy
nthesi
soft
hiazol
i
dinonesusi
ngsubst
it
utedt
hiosemi
car
bazi
desand

di
met
hylacet
ylenedi
car
boxy
lat
einr
efl
uxet
hanolwhi
chal
sor
equi
redpl
anarl
i
qui
d
18
chr
omat
ogr
aphyf
orpur
if
icat
ion(
Scheme3)
.

8
 Di
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tat
ion2018-
19

Scheme2.Aci
dmedi
atedsy
nthesi
soft
hiazol
i
dinoneusi
ngt
wost
epr
eact
ion.

Scheme3.Sy
nthesi
soft
hiazol
i
dinonei
nref
luxet
hanol
.

Recent
ly,Dasandco-
wor
ker
sdescr
ibedani
mpr
ovedr
egi
osel
ect
ivemet
hodol
gyt
o
19
access t
hiazol
i
dinones usi
ng nano-
CuFe2O4 as a cat
aly
st (
Scheme 4)
.

Unf
ort
unat
ely
,mostoft
heaf
orement
ionedsy
nthet
icendeav
our
ssuf
ferf
rom one

dr
awbackoranot
hersuchasuseofamet
alcat
aly
st,t
edi
ouswor
k-up,l
i
mit
ed

9
 Di
sser
tat
ion2018-
19

subst
rat
escope,
poorr
egi
osel
ect
ivi
ty,
prol
ongedr
eact
iont
ime,
elev
atedt
emper
atur
e

and moi
stur
e/ai
rsensi
ti
vi
ty.Thus,t
hedev
elopmentofaf
aci
l
emul
ti
component

appr
oach t
o sul
fonami
de–t
hiazol
i
dinonehy
bri
dsi
spot
ent
ial
l
yimpor
tant
.Int
his

cont
ext
, our r
esear
ch gr
oup descr
ibed t
he mul
ti
component sy
nthesi
s of

sul
fonami
de–t
hiazol
i
dinonehy
bri
dsusi
ngaonepotr
eact
ionofsul
fony
lhy
drazi
des,

i
sot
hiocy
anat
es,
anddi
alky
lacet
ylenedi
car
boxy
lat
esi
net
hanolatr
oom t
emper
atur
e
20
wi
thoutt
heai
dofacat
aly
st(
Scheme5)
.

Scheme4.Mul
ti
componentsy
nthesi
soft
hiazol
i
dinonesusi
ngnano-
CuFe2O4asacat
aly
st.

Exper
iment
alSect
ion:

Scheme5.Mul
ti
componentSy
nthesi
sofsul
fonami
de–t
hiazol
i
dinonehy
bri
dsunderambi
ent

condi
ti
ons.

10
 Di
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tat
ion2018-
19

Tabl
e 1. Subt
rat
e scope of t
he pr
esent mul
ti
component r
eact
ion t
o access
a
sul
fonami
de–t
hiazol
i
dinonehy
bri
ds.

Sr
.No. React
ant React
ant React
ant Pr
oduct Yi
eld(
%)

1 2 3 4

91
4a

4b 89

4c 81

11
 Di
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tat
ion2018-
19

4d 89

4e 83

a
React
ionconduct
edona0.
5mmolscal
ein2mLofet
hanolusi
ngequi
mol
arr
ati
oof1,2

and3.

21
Basedoni
sol
ati
onofpr
oduct
sandexi
sti
ngl
i
ter
atur
e, apl
ausi
blemechani
sm i
s

out
li
nedi
nScheme6.Ther
eact
ioni
sassumedt
ost
artwi
thanucl
eophi
l
icat
tackby

t
hesul
fony
lhy
drazi
deatt
heel
ect
rophi
l
iccar
bonofi
sot
hiocy
anat
etof
ormt
heN,
N’-

subst
it
utedt
hiour
eai
nter
medi
ateI
,whi
chwasi
sol
atedandconf
ir
medbyNMR.The

St
ermi
nalofi
nter
medi
ateI
,bei
ngsof
t,mayr
eadi
l
yreactwi
tht
heacet
yleni
ccar
bon

ofmol
ecul
e3t
ogener
atei
nter
medi
ateI
I,whi
chmayunder
goaf
aci
l
eint
ramol
ecul
ar

r
ingcl
osur
ewi
thconcomi
tantel
i
minat
ionofal
cohol
tof
urni
sht
hedesi
redpr
oduct4.

12
 Di
sser
tat
ion2018-
19

Concl
usi
on:

A mul
ti
componentsy
nthesi
s ofsul
fonami
de–t
hiazol
i
dinone hy
bri
ds has been

dev
elopedusi
ngaone-
potr
eact
ionofsul
fony
lhy
drazi
des,i
sot
hiocy
anat
es,and

di
alky
lacet
ylene di
car
boxy
lat
es undercat
aly
st-
fr
ee condi
ti
ons.The oper
ati
onal

si
mpl
i
cit
y,mi
l
dcondi
ti
ons,shor
treact
iont
ime,wi
descopeandf
unct
ionalgr
oup

t
oler
ance,andabsenceoft
edi
ousi
sol
ati
onandpur
if
icat
ionmet
hodsmaket
his

pr
ocessenv
ironment
all
ybeni
gnandhi
ghl
yusef
ulf
oracademi
aandi
ndust
ry.

Gener
alI
nfor
mat
ion.1HNMRspect
rawer
erecor
dedonJeolResonanceECX-
500I
I

(
500MHz)
;Chemi
calshi
ft
s(i
nppm)andcoupl
i
ngconst Ji
ant( nHz)ar
ecal
i
brat
ed

ei
therr
elat
ivet
oint
ernalsol
ventt
etr
amet
hyl
sil
aneTMS(
H =0.
00ppm)orCDCl
3(
H

=7.
256ppm)
.I he1HNMRdat
nt a,t
hef
oll
owi
ngabbr
evi
ati
onswer
eusedt
hroughout
:

s=si
ngl
et,
d=doubl
et,
t=t
ri
plet
,dd=doubl
edoubl
ets,
dt=doubl
etr
ipl
ets,
andbr
s=

br
oadsi
ngl
et.13CNMRspect
rawer
erecor
dedonJeolResonanceECX-
500I
I(125

MHz)i
nCDCl
3;chemi
calshi
ft
sar
ecal
i
brat
edr
elat
ivet
oCDCl
3(
c=77.
0ppm)
.IR

13
 Di
sser
tat
ion2018-
19

spect
rawer
erecor
dedonPer
kinEl
merFT-
IR spect
romet
er-
spect
rum t
wo.The

r
eact
ionswer
emoni
tor
edbyThi
nLay
erChr
omat
ogr
aphy(
TLC)usi
ngMer
cksi
l
ica

gelpl
ates( ck® 60F254)
Mer .Isot
hiocy
anat
esanddi
alky
lacet
ylenedi
car
boxy
lat
eswer
e

pur
chasedf
rom Al
faAesarorSi
gmaAl
dri
ch.Thesul
fony
lhy
drazi
deswer
epr
epar
ed
26
accor
dingt
oli
ter
atur
epr
ocedur
e. Sol
vent
swer
epur
if
iedpr
iort
oit
suse.

Gener
al pr
ocedur
e f
or t
he t
hree-
component sy
nthesi
s of

Sul
fonami
de–Thi
azol
i
dinonehy
bri
ds4a–4e:

A mi
xtur
e ofsul
fony
lhy
drazi
de 1 (
0.5 mmol
),i
sot
hiocy
anat
e2(
0.5 mmol
),

di
alky
lacet
ylenedi
car
boxy
lat
e3(
0.5mmol
)andet
hanol(
2mL)
,pl
acedi
nagl
ass

v
essel
,wasst
ir
redatr
oom t
emper
atur
efor1h.Af
tercompl
eti
onoft
her
eact
ion

(
TLC)
,ay
ell
owsol
i
dappear
ed,whi
chwasf
il
ter
edandwashedwi
thcoolet
hanolt
o

gi
vet
hepur
epr
oduct4.Thepr
oduct
swer
echar
act
eri R,1H-
zedbasedonFTI NMR,

and13C-
NMR.

Spect
ral
Dat
aoft
heSy
nthesi
zedPr
oduct
s(4a-
4e)
:

Z)
( -
Met
hyl
-2-
(Z)
( -
4-oxo-
3-pheny
l-
2-(
2-t
osy
lhy
drazono)
thi
azol
i
din-
5-y
li
dene)
acet
ate
18
(
4a) :Pal
eyel
l
ow sol
i
d(91%)
,m.
p.220-
221˚
C.I
R( 600cm-1)
4000- :νmax =3424,

3181,
1714,
1699, 1610.1HNMR(
1639, CDCl
3,500MHz)
:δH (
ppm)7.
62(
d, J=s
2H,

8.
5Hz,
ArH)
,7.
43-7.
50(
m,3H,
ArH)
,7.
193(
d, J=8.
2H, 0Hz,
ArH)
,7.
26-
7.29(
m,2H,

14
 Di
sser
tat
ion2018-
19

Ar
H),7.
00(
s,1H,CH)
,6.
56(
s,NH)
,3.
89(
s,3H,OCH3)
,2.
39( .13CNMR
s,3H,CH3)

(
CDCl
3,125MHz)
:δc(
ppm)166.
0,164.
1,161.
6,144.
6,139.
6,134.
1,133.
2,129.
4,

129.
1,128.
5,127.
5,117.
9,52.
8,21.
6.

Z)
( -
Ethy
l-
2-(
(Z)
-3-
(4-
nit
ropheny
l)-
4-oxo-
2-(
2-(
pheny
lsul
fony
l)hy
drazono)
thi
azol
i
din-
5-

y
li
dene)
acet
ate(
4b)
:Yel
l
owsol
i
d(89%)
,m.
p.217-
218˚
C.I
R( 600cm-1)
4000- :νmax=

3553,3308,3244,3056,2986,2863,1711,1638,1610,1520.1H NMR(
CDCl
3,500

MHz)
:δH (
ppm)8.
30(
d, J=9.
2H, 0Hz,
ArH)
,7.
76(
d, J=8.
2H, 0Hz,
ArH)
,7.
61(
t,1H,

J=7.
0Hz
,Ar
H),
7.40-
7.52(
m,4H,
ArH)
,7.
02(
s,1H,
CH)
,6.
77(
brs,
NH)
,4.
35(
q, J
2H,

=7.
0Hz,CH2)
,1.
36(
t,3H,J=7. .13CNMR(
0Hz,CH3) CDCl
3,125MHz)
:δc(
ppm)

165.
4(CO)
,163.
4(COO)
,159.
8(C=N)
,147.
6(Ar
),138.
4(CH)
,138.
4(Ar
),137.
0(Ar
),

133.
9(Ar
),128.
9(Ar
),128.
6(Ar
),128.
4(Ar
),124.
3(Ar
),119.
3(=C)
,62.
3(CH2)
,14.
2

(
CH3)
.

15
 Di
sser
tat
ion2018-
19

Z)
( -
Met
hyl
2-(
(Z)
-3-
(4-
fl
uor
opheny
l)-
2-(
2-(
(4-
met
hoxy
pheny
l)sul
fony
l)hy
drazono)
-4-

oxot
hiazol
i
din-
5-y
li
dene)
acet
ate(
4c)
:Yel
l
owsol
i
d(81%)
,m.
p.225-
226˚
C.I
R(4000-

600cm-1)
:νmax =3168,3053,1714,1690,1640,1598,1510.1H NMR(
CDCl
3,500

MHz)
:δH (
ppm)7. d,2H,J=9.
66( 0Hz,Ar
H),7.
15(
t,2H,J=8.
0Hz,Ar
H),7.
21-
7.27

(
m,2H,mer
gewi
thCDCl
3,Ar
H),6. d,2H,J=9.
86( 0Hz,Ar
H),6.
97(
s,1H,CH)
,6.
92

(
brs,
NH)
,3.
85(
s,3H,
CH3)
,4.
33(
q, J=7.
2H, 5Hz,
CH2)
,1.
35(
t, J=7.
3H, 0Hz,
CH3)
.
13
CNMR(
CDCl
3,125MHz)
:δc(
ppm)165.
5(CO)
,163.
9(d,J=40Hz,Ar
),163.
5

(
COO)
,161.
6(Ar
),160.
2(C=N)
,139.
2(CH)
,130.
6(Ar
),129.
5( J=8.
d, 7Hz,
Ar)
,129.
1

(
Ar)
,128.
6(Ar
),118.
4(=C)
,116.
2(d,J=23.
7Hz,Ar
),113.
9(CH)
,62.
1(OCH2)
,55.
7

(
OCH3)
,14.
2(CH3)
.

Z)
( -
Ethy
l-
2-(
(Z)
-2-
(2-
((
4-ni
tr
opheny
l)sul
fony
l)hy
drazono)
-4-
oxo-
3-pheny
lthi
azol
i
din-
5-

y
li
dene)
acet
ate(
4d)
:Li
ghty
ell
owsol
i
d(89%)
,m.
p.225-
226˚
C.I
R( 600cm-1)
4000- :

16
 Di
sser
tat
ion2018-
19

ν
max =3324,3251,3185,3058,2980,1720,1688,1638,1611.1HNMR(
CDCl
3,500

MHz)
:δH (
ppm)8. d,2H,J=9.
19( 0Hz,Ar
H),7. d,2H,J=8.
88( 5Hz,Ar
H),7.
49-
7.54

(
m,3H,Ar
H),7.
23-
7.28(
m,2H,mer
gedwi
thCDCl
3,Ar
H),7.
01(
s,1H,CH)
,6.
70(
brs,

NH)
,4. q,2H,J=7.
35( 0Hz,CH2)
,1.
36(
t,3H,J=7. .13CNMR(
5Hz,CH3) DMSO-
d6,

125MHz)
:δc(
ppm)165.
5(CO)
,163.
5(COO)
,150.
0(Ar
),140.
7(C=N,
CH)
,133.
6(Ar
),

129.
8(Ar
),129.
5(Ar
),129.
0(Ar
),128.
9(Ar
),127.
9(Ar
),124.
4(Ar
),123.
9(Ar
),115.
9

(
=C)
,61.
7(OCH2)
,14.
0(CH3)
.

Z)
( -
Met
hyl
-2-
(Z)
( -
3-(
4-ni
tr
opheny
l)-
2-(
2-(
oct
ylsul
fony
l)hy
drazono)
-4-
oxot
hiazol
i
din-
5-

y
li
dene)
acet
ate(
4e)
:Yel
l
owsol
i
d(83%)
,m.
p.185-
186˚
C.I
R( 600cm-1)
4000- :νmax=

1
3166,
2924,
2858,
1715,
1697,
1635,
1608,
1524.HNMR(
CDCl
3,500MHz)
:δH (
ppm)

8.
38(
d, J=9.
2H, 0Hz,
ArH)
,7.
62(
d, J=9.
2H, 0Hz,
ArH)
,7.
048(
s,1H,
CH)
,6.
76(
brs,

NH)
,3.
90(
s,3H,OCH3)
,3.
08(
t,2H,J=8.
0Hz,CH2)
,1. p,2H,J=7.
77( 5Hz,CH2)
,

1.
32-
1.40(
m,2H,CH2)
,1.
15-
1.30(
m,8H,(
CH2)
4),0.
870(
t,3H,J=6. .13C
5Hz,CH3)

NMR(
CDCl
3,125MHz)
:δc(
ppm)165.
8(CO)
,163.
6(COO)
,161.
6(C=N)
,147.
7(Ar
),

138.
7(CH)
,138.
5(Ar
),128.
6(Ar
),124.
6(Ar
),118.
9(=C)
,53.
0(CH2)
,50.
2(OCH3)
,

31.
7(CH2)
,28.
9(CH2)
,28.
9(CH2)
,28.
2(CH2)
,23.
2(CH2)
,22.
6(CH2)
,14.
0(CH3)
.

17
 Di
sser
tat
ion2018-
19

Ref
erences:

1)J.B.Manl
ey,
P.Anast
asandB.W.CueJr
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i
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4)F.Lor
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utr
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andB.A.Ar
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nthesi
s,Wi
l
ey-
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5)C.Hul
me,
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az,
G.Mar
ti
nez
-Ar
iza, RecentAdv
F.MeddaandA.Y.Shaw, ancesi
n
Mul
ti
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ionChemi
str
y:Appl
i
cat
ionsi
nSmal
lMol
ecul
eDr
ugDi
scov
ery
,
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l
ey-
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2015.

6)T.Kaur
,P.Wadhwa,
S.Bagchi
andA.Shar
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,2016,
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7)N.Shar
ma,
U.K.Shar
ma,
N.M.Mi
shr
aandE.V.VanderEy Adv
cken, .Sy
nth.Cat
al.
,
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8)U.K.Shar
ma,
N.Shar
ma,
D.D.Vachhani
andE.V.VanderEy Chem.Soc.Rev
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44,
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9)Shav
eta,
S.Mi
shr
aandP.Si Eur
ngh, .J.Med.Chem.
,2016,
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10)F.W.Mur
egi
andA.I
shi
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ugDev
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,2010,
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11)A.Mar
bl Dr
e, ugs,
1971,
1,109

12)M.Pi
ppel
,B.D.Al
l
ison,
V.K.Phuong,
L.Li
,M.F.Mor
ton,
C.Pr
ender
gast
,X.Wu,
N.P.
Shankl
eyandM.H.Rabi
nowi
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, oor
g.Med.Chem.Let
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,2009,
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13)D.Hav
ryl
yuk,
L.Mosul
a,B.Zi
menkov
sky
,O.Vasy
lenko,
A.Gzel
l
aandR.Lesy
k,Eur
.J.
Med.Chem.
,2010,
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5012.

14)C.V.Kav
itha,
Basappa,
S.N.Swamy
,K.Mant
eli
ngu,
S.Dor
eswamy
,M.A.Sr
idhar
,J.S.
Pr Bi
asadandK.S.Rangappaa, oor
g.Med.Chem.
,2006,
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15)S.Schenone,
O.Br
uno,
A.Rani
se,
F.Bondav
all
i
,W.Fi
l
ippel
l
i,G.Fal
cone,
L.Gi
ordano
andM.R.Vi
tel
l
i,Bi
oor
g.Med.Chem.
,2001,
9,2149.

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16)M.Bal
l
abeni
,R.Bal
l
ini
,F.Bi
gi,
R.Maggi
,M.Par
ri
ni,
G.Pr
edi
eri
andG.Sar
tor
i,J.Or
g.
Chem.
,1999,
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17)B.Fábi
án,
V.Kudar
,A.Csámpai
,T.Z.NagyandP.Sohár
,J.Or
ganomet
.Chem.
,2007,
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5621.

18)A.A.Hassan,
A.A.Al
y,T.I
.M.Bedai
r,A.B.Br
ownandT.I
.El
-Emar
y,J.Het
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cl.
Chem.
,2014,
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19)G.Pal
,S.Paul NewJ.Chem.
andA.R.Das, ,2014,
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iandKr
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A.Khar
bandaandA.Shar Asi
ma, anJ.Or
g.Chem.
,2018,
7,634.

19
 Di
sser
tat
ion2018-
19
1
Copi
esofSpect
ras4a-
4e(H&13CNMR)
:
1
Z)
HNMRof( -
Met
hyl
-2-
(Z)
( -
4-oxo-
3-pheny
l-
2(2-
tosy
lhy
drazono)
thi
azol
i
din-
5-y
li
dene)
acet
ate
(
4a)
:

13
CNMRof( Z)
-Met
hyl
-2-
(Z)
( -
4-oxo-
3-pheny
l-
2-(
2-t
osy
lhy
drazono)
thi
azol
i
din-
5-y
li
dene)
acet
ate(
4a)
:

20
 Di
sser
tat
ion2018-
19
1
HNMRof( Z)-
Ethyl
-2-
((Z)
-3-
(4-
nit
ropheny
l)-
4-oxo-
2-(
2(pheny
lsul
fony
l)hy
drazono)
thi
azol
i
din-
5-
yl
idene)
acet
ate(4b):

13
CNMRof( Z)
-Et
hyl-
2-(
(Z)
-3-
(4-
nit
ropheny
l)-
4-oxo-
2-(
2-(
pheny
lsul
fony
l)hy
drazono)
thi
azol
i
din
-
5-y
li
dene)
acet
ate(4b)
:

21
 Di
sser
tat
ion2018-
19
1
HNMRof( Z)-
Methyl
2-(
(Z)
-3-(
4-f
luor
opheny
l)-
2-(
2-(
(4-
met
hoxy
pheny
l)sul
fony
l)hy
drazono)
-4-
oxot
hiazol
i
din-
5-y
li
dene)
acetat
e(4c):

13
CNMRof( Z) -
Methyl2-
(Z)
( -
3-(4-
fl
uoropheny
l)-
2-(
2-(
(4-met
hoxy
pheny
l)sul
fony
l)hy
drazono)
-
4-
oxot
hiaz
oli
din-5-
yl
idene)acetate(4c)
:

22
 Di
sser
tat
ion2018-
19
1
HNMRof( Z)
-Et
hyl-
2-(
(Z)
-2-
(2-
((
4-ni
tr
opheny
l)sul
fony
l)hy
drazono)
-4-
oxo-
3-pheny
lthi
azol
i
din-
5-
yl
idene)
acet
ate(4d)
:

13
CNMRof( Z)
-Et
hyl-
2-(
(Z)
-2-
(2-
((
4-ni
tr
opheny
l)sul
fony
l)hy
drazono)
-4-
oxo-
3-pheny
lthi
azol
i
din
-
5-y
li
dene)
acet
ate(4d)
:

23
 Di
sser
tat
ion2018-
19

1
H NMR of (Z)
-Met
hyl
-2-
(Z)
( -
3-(
4-ni
tr
opheny
l)-
2-(
2-(
oct
ylsul
fony
l)hy
drazono)
-4-
oxot
hiazol
i
din-
5-y
li
dene)
acet
ate(
4e)
:

13
C NMR of ( Z)
-Met
hyl
-2-
(Z)
( -
3-(
4-ni
tr
opheny
l)-
2-(
2-(
oct
ylsul
fony
l)hy
drazono)
-4-
oxot
hiazol
i
din-
5-y
li
dene)
acet
ate(
4e)
:

24