Design, synthesis and characterization of functionalized pyrazole derivatives bearing amide and sulfonamide moieties from aza-aurones

Article abstract of DOI:10.1007/s12039-020-01792-3

Abstract: In this work, we report the synthesis of new pyrazole derivatives bearing amide and sulfonamide frameworks from aza-aurones. Firstly, the intermediate spiropyrazolines were obtained through a highly regioselective 1,3-dipolar cycloaddition of nitrilimines with aza-aurones. Subsequently, the obtained cycloadducts were subjected to hydrochloric acid in hot ethanol which conducts to 5-(2-aminobenzoyl)-3,4-diaryl-1-phenylpyrazoles. Finally, the target compounds were obtained separately by the action of acetic anhydride, benzoyl chloride and tosyl chloride on the intermediates 2-aminobenzoylpyrazoles, respectively. Structures of all the synthesized compounds were established using IR, ¹H NMR and ¹³C NMR and mass spectroscopy. Graphic Abstract: Synthesis and characterization of novel heterocyclic systems encompassing pyrazole derivatives from aza-aurones are reported. The synthetic routes used in this work are efficient and relevant, involving the 1,3-dipolar cycloaddition and alkylation reactions. The outcomes show that spectroscopic data fit the structure of all synthesized compounds.[Figure not available: see fulltext.]

Full text of DOI:10.1007/s12039-020-01792-3

J. Chem. Sci. (2 0 2 0 ) 13 2: 86
Ó In di an Aca dem y of Sc i en c es
h t tp s: / / d o i .o r g /1 0 . 1 0 07 /s 1 20 39 - 02 0- 01 79 2- 3 Sadhan
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REGULAR ARTICLE
Design, synthesis and characterization of functionalized pyrazole
derivatives bearing amide and sulfonamide moieties from aza-aurones
a
M OHA MM ED CHAL KHA , MOHA MED B AKHOUCH
a ,b
, MOHA MED AKHAZZAN E
a
a nd
a, c
d
d
M OHAM ED BOUR ASS , YOHANN NI COL AS , GHALI AL HOUAR I
,
M OHAM ED EL YAZI DI
a,
*
a
En g in eer in g Lab or a to r y of O rg an om et al l ic and Mol ecu lar Mat er i al s and Env ir onm ent , F acul t y of Sc i en c es
Dh a r EL Ma hr az, U niv er s i ty S id i Mo ham ed B e n Ab de l la h, P . O. B ox 179 6 (A t la s ), 300 00 F es , Mor o c co
b
De pa rt m en t of Ch e m is t ry , F acu l ty of S ci ences , C hou a ¨ı b Do uk kal i Un ive r s i ty , P .O . B ox 20, 240 00 El Ja d i da ,
M o ro cc o
c
Un i ve rs i t e´ S id i Mo ha m ed Be n A bdel l ah, C it e´ de l ’i nnov at i on, F es , Mor o cco
In s t i tu t de s S cie nc es Mo l e´ cu la ir es , UMR - C NR S 525 5, Un i ver s it e´ of B ord ea ux, 351 cou rs de l a Li b e´ r at i o n ,
3 4 0 5 Tal en ce Ce dex , F ra nc e
d
3
E- ma il : el ya zi di mo ha m ed @h ot m ai l.c om
MS r ecei v ed 8 M ar ch 2 02 0 ; r ev i s ed 3 0 A p r i l 2 0 2 0; accep t ed 5 M ay 2 0 2 0
Abstract. I n th is w or k, w e r epo r t the s ynt hes i s o f new p yr azol e der iv ati v es bea ri ng am i de and s ul fo na m i de
fr am e w or ks f ro m az a- aur on es . F ir s tl y, t he i nt erm ed i at e s pi ro pyr azo li ne s wer e obt a i ned t hro ugh a h ig h l y
re g i os e le cti ve 1, 3- di po l ar cy cl oad di t io n of ni t ri li m i nes wi t h aza- aur one s . S ub s equ ent ly , t he o bt a i ne d
c y cl o ad du ct s w er e s ub j ec ted to hy dr oc hl or ic aci d i n hot et ha nol wh i ch con duc t s t o 5- (2 -am i no b enz oy l) - 3, 4 -
d i ar y l - 1- ph eny l py r azo le s . F in all y, th e t arge t com pou nds wer e ob t ai ned s epa rat el y by t he act i on of a ce t i c
a n hy d r id e, be nz oy l ch lo r id e an d to s y l chl or id e on t he i nt erm ed i at es 2- am i nobe nzoyl pyr azol es , res p ec ti v e ly .
1
1 3
St ru c t u r es of al l th e s yn t he s ize d co mp oun ds wer e es t abl i sh ed us i ng IR , H NMR and C NMR an d ma s s
s p ec t ro s co py .
Keywords. A za- au ro ne ; ni tr il im in e; s pi ro pyraz ol i ne; pyr az ol e; am i de; s ul fo nam i de.
2
4 ,2 5
1
. Introduction
c om poun ds a nd 1,3 -d ipol ar c yc loa dd iti on.
The r e
is a ge ne r al c onse ns us th at 1,3 -d ipol ar c yc loa ddition
r ea c ti on is e mp loye d a s th e m ost pr a ct ic a l m e thod to
pr ov ide hi ghly sub sti tut ed pyr a z ole s.
Az a- a ur one s , na m el y 2- a r ylid en ei ndo lin- 3( 2 H) - one s
He te r o cy c l ic c o mp o un ds ar e of g rea t i nt er es t , owi ng to
a w id e v a rie t y o f ap pl i ca ti o ns t he y po ss es s in m an y
2
6
1– 6
fie l d s . Am o n g t he he t er oc yc li c co mp ou nd s, pyr a z ole
d e ri v a tiv e s c o n s tit ut e t he mo st st u di ed co mp oun ds due
2
7 – 3 1
a re kn own to pos se ss va r iou s bi olog ic a l a ct ivi ti e s,
2
7– 15
7 ,3 0
2 8 , 2 9 ,3 1
t o i ts wi d es p re a d ap pl i ca ti o ns .
I n ad di t i on , p yr az ol e
in cl udi ng a nti ca nc e r ,
3
a nti ma la r ia l,
a nd
2
m o i e ty is a n a c ti v e ph ar ma co ph or e wh ic h en t e rs in to
t h e d e s ig n o f a b ro ad sp ec tr u m of na t ur al an d sy nt he tic
a nti ba ct er i al . I t ha s a lso be e n f oun d th at th ese inte r -
e sti ng c om poun ds a re use d a s ke y bu ildi ng bloc ks to
1
6 , 17
3
3 –3 8
b i o ac ti v e c o mp o un ds .
i n g s u lf o n a mi d e an d am id e mo ie t ie s ar e an i mp or ta nt
Fu rt h er , t he py r azo le be a r-
de ve lo p m an y he te r oc yc li c c om poun ds.
ti on, in doli n- 3- one m oie ty is f r eq uen tly f oun d in na t-
In a ddi-
1
8
3
9 – 4 3
s c af fo ld fo r th e r a pe ut i c ag en t s, n ame ly ce l ecox ib,
ur a l pr od uct s a nd bi olog ic a lly a ct ive m ole c ule s .
1
9
20
d e ra c o x ib , ri mo nab an t , su l fa ph en az ol e, pyr a z o-
21
He nc e, th e in tr odu ct ion of th is f r am e wor k in th e c or e of
th e de si gne d c om poun ds m ay le a d to ne w he te r oc yc le s
wit h pr om isi ng pha r m ac ol ogi ca l a ct ivi ty.
As pa r t of ou r on goin g r es ea r c h, we a im to s yn-
th es iz e he te r oc yc li c c om poun ds f or th er a pe utic
2
2
23
fu r i n , d if e n a miz ol e …, et c . ( Fi gu re 1) .
In g e n e ra l, th e p yr azo l e co mp ou nd s ar e pr e pa re d
u s i ng tw o c o n v e nt i on al ap pr oa ch es: cy cl o con de nsa -
t i o n o f h y d ra z in e d eri v at iv es wi th 1, 3- di el e ct r ophi li c
*
F o r co rr e sp on den ce
Electronic supplementary material: The online version of this article (https://doi.org/10.1007/s12039-020-01792-3) contains
supplementary material, which is available to authorized users.

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J. Chem. Sci. (2 020) 1 32: 86
4
4 – 4 9
p u rp o s e s .
Her e, we r epo r t t he sy nt h es is of pol y- f or 20 m in. The n, th e pr op er a lde hy de ( 0.01 5 mol )
s u b s tit u te d p y ra z o l e- be ar i ng am id e an d su l fo na m ide di ssol ve d in 4 m L of e tha no l wa s a dde d dr opw is e
fr a m e wo rk s fro m az a- au ro ne s. Th e sy nt h es is pr oc e ed s th ro ugh th e dr op ping f unn el . The m ixt ur e wa s re fl uxe d
t h r o u g h tw o su cc es si ve r eac t io ns : 1 ,3- dip ola r un til th e f or ma t ion of a n or a nge sol id whic h w as
c y c lo a d d i ti o n a n d N- al ky la ti o n.
fi lte r e d a nd wa she d th or ough ly wit h wa ter . The
ob ta ine d sol id wa s r ec r yst a lli ze d in e tha no l to a f f or d
a za - a ur one s in m ode r at e to goo d yi el d, whi c h w as
use d wit hout f ur the r pur i fic a tio n.
2
. Experimental
2
. 1 General information
2.2 b Synthesis of spiropyrazolines (2aa–2db): T o a
sol uti on of a ppr opr i at e a za - a ur one 1 ( 1 m mol ) in 20
m L of c hlo ro fo rm , th e pr op er a- ch lor oa r y lide ne p
he nyl hyd ra z one ( 1.2 m mol ) a nd tr i me thy la mine ( 1.2
m mol ) wa s a dde d. The m ixt ur e wa s he ld un der s tir r ing
a t r oom te m pe ra t ur e, a nd th e pr og re ss of th e re a c tion
wa s m onit or e d by TLC . Af te r th e r ea c ti on c om ple te d,
th e sol ve nt wa s r em ov ed to pr ov ide a c ru de p r oduc t.
The obt a ine d r es idu e wa s c ry sta ll iz ed in e tha nol a nd
th e f or me d pr e ci pit at e wa s fi lte r e d a nd wa shed w ith
c old e tha no l.
Al l re a g e n ts a n d so l ve nt s wer e of AR gr ad e . The se
c h e mi c a ls we re p ur ch as ed f ro m Si g ma- Ald r i ch a nd
o t h er c o mm e rc ia l su pp l ie rs , an d wer e u sed wit hout
fu r t h e r p u ri fic a ti on . Th e pr o gr es s of t he r eac t ion s wa s
m o ni to re d b y T LC, pe rf o rme d on p re- co at e d Me r c k
s i l i ca g e l 6 0 F 2 5 4 pl a te s. Co lu mn ch ro ma to gr ap hy wa s
c ar rie d o u t u s in g M er ck si l i ca ge l ( 70 -2 30 m es h) ,
e l ut in g wi th n -h e xa ne an d et h er so l ut i on . Me l tin g
p o i nt s we re d e te r mi n ed u si ng a Ko fler Be nch a ppa r a-
t u s . IR s p e c tra wer e r eco rd ed u si ng a Fo ur i er Tr a ns-
1
fo r m Br u k e r Ver t ex 70 Sp ec tr om et e r. H a nd
1
3
C NM R s p e c tra wer e r eco rd ed at r oo m t empe r a tur e 2.2 c Synthesis of 5-(2-aminobenzoyl)-3,4-diaryl-1-
o n a Br u k e r Av a nc e I I 30 0 Ul tr a- Sh i el d ( 30 0 MHz f or phenylpyrazoles (3aa–3db): I n a 10 0 m L fl a sk
1
13
H a n d 7 5 M Hz f or C) sp ec tr o met er u si ng C DCl
3
e qui ppe d wit h a c onde ns er , c yc loa dd uc t 2 ( 1 mmol)
a n d DM S O-d s o l ve nt s. H an d C NM R ch e mi ca l wa s di ssol ve d in e tha no l ( 40 m L) , a nd th re e d r ops of
1
13
6
s h i f ts (d) a re e x p res se d i n p art s pe r mi l li o n ( pp m) wit h hyd r och lor i c a ci d wa s a dde d to th e sol uti o n. The
re fe re n c e to th e so l ve nt u sed , an d p ro to n cou pli ng m ixt ur e wa s r efl ux ed unt il th e c om ple ti on of the
c o n s ta n ts ( J) a re r epo r te d i n he rt z ( Hz) . The spi n r ea c ti on, a s m onit or e d by TLC . Af te r th e 3/ 4 of the
m u l ti p li ci ti e s a re r epo r te d as si n gl et ( s) , do u ble t ( d) , sol ve nt wa s r em ov ed by va c uum , 60 m L of c ol d w at er
t ri p l et (t ), mu l ti p l et ( m), d oub l et of d oub l e ts ( dd) , wa s a dde d. The f or me d pr e ci pit at e wa s fi lte re d a nd
d o u b le t o f tr ip l et s ( dt ) an d br o ad ( br ). M as s spe c tr a wa she d th or ough ly wit h wa te r . The ob ta ine d soli d w as
we re p e rfo rm ed b y t he CES AM O ( Bor de au x, F ra nc e ) pur i fie d by r ec r yst a lli za ti on in e tha no l.
o n a Q E x a c tiv e M as s Sp ec tr om et e r ( The rmo ). The
i n s t ru me n t is e q ui p pe d wi th an ES I so ur ce a nd th e
2.2 d Synthesis of pyrazoles-bearing benzamide
s p e c tra we re re c or de d i n a po si t i ve mo de . The spr a y
v o l t a g e wa s ma i nt a in ed at 3 200 V an d ca pi l l ar y te m -
p e ra tu re wa s s e t a t 32 0 °C. Sa mpl e s wer e i nt r odu ce d by
i n j e c tin g th r o u g h a 2 0 lL sa mp le l oo p i nt o a 300 lL/
m i n fl o w o f me t h an ol f ro m t he LC pu mp . Aza - au ro ne s
moiety (4aa–4db): To a sol uti on of a ppr opr ia te
c om poun d 3 ( 1 m ol) in 20 m L of a bsol ute D CM ,
tr i et hyla m ine ( 2 m L) wa s a dde d a nd th e sol uti on w as
st ir r ed a t 0°C in a n ic e ba th . B en zoy l c hlo ri de ( 1 mol )
wa s a dde d in sm a ll por t ion s whi le m ai nta in ing the
te m pe ra t ur e up to 0 °C . The n, th e r ea c ti on m ixt ur e w as
ke pt un der m ag ne tic st ir r ing a t r oom te m pe ra t ur e . The
pr og re ss of th e r ea c ti on wa s m onit or e d by TLC . A ft er
c om ple ti on of th e r ea c ti on, th e m ixt ur e wa s tr a n sf e r r e d
in to a se pa r at or y f unn el a nd wa she d se ve r al ti m e s w ith
wa te r . The or ga ni c la ye r wa s dr ie d ove r a nhydr ous
sod ium sul f at e ( Na S O ) a nd th e sol ve nt wa s r em ove d
1
p re p a re d a c co r d in g t o t he p ro ced ur e de sc ri b ed in th e
wa s u s e d a s s ta rt i ng ma te ri a l i n t hi s wo rk and we r e
3
5 ,5 0 , 5 1
l i t era tu r e.
2
2
. 2 General procedures
2
4
. 2 a Synthesis of aza-aurones (1a–b): I n a 10 0 m L
und er r ed uc ed pr e ssur e . The r es ult ing r es idue w as
pur i fie d by c olu mn c hr om at ogra phy usi ng he xa ne –
e the r m ixt ur e ( 4:1 ).
t h r e e -n e ck e d fl a sk co nt a in in g 5 0 mL o f NaOH ( 2N) ,
e q u ip p ed wi th a co nd en se r, d ro pp in g f un nel a nd a
n i t ro g e n b u b b le r. Th e aq ue ou s so l ut i on o f NaOH wa s
p u rg e d wi th a n it r og en st r ea m un d er ma gn et i c st ir r ing
fo r 1 0 mi n . Di ac et y li nd ox yl ( 0.0 1 mo l) was a dde d to 2.2 e Synthesis of pyrazole bearing acetamide moiety
t h e s o lu t io n a n d th e mi xt u re was h eat ed un d er st ir r ing (5aa–5db): I n a 50 m L fl as k e qui ppe d w ith a

J. Chem. Sci. (2 0 2 0 ) 13 2: 86
P age 3 of 8 86
Figure 1. P yr az ol es be ar in g am i de and s ul fo nam i de m oi et ie s ava il ab l e as dr ugs .
c o n d e n s e r, 5 -(2 - a m in ob enz oy l )p yr azo l e ( 5 mm ol) a nd r es idu e wa s c ry sta ll iz ed in a m ixt ur e of Et OH–DC M
a cet ic a n h y d rid e ( 20 mL ) wer e i nt r od uce d. The ( 5:3 ).
m i x tu re wa s s ti rre d at r eflu x u nt il t he co mp le ti on of
t h e re a c ti o n , a s ev i de nce d b y TL C. Th e r ea c ti on
3
. Results and Discussion
m i x tu re wa s p o u red i nt o i ce -c ol d wat e r ( 20 0 m L) a nd
e x t r a ct e d wi th DCM ( 3 x 2 0 mL ). Th e DCM l aye r wa s
wa s h e d th r ic e wit h a sa t ur at ed so l ut i on of Na HCO3
a n d wa te r . T h e o rg an i c l ay er was d ri ed ov er an h ydr ous
3.1 Synthesis of spiropyrazolines (2)
S pir op yr az ol ine s 2 we r e pr e pa re d vi a 1,3 -dip ola r
c yc loa dd iti on r ea c ti on of N- phe nyl -C- ar y lni tr ilim ine s
wit h a za - a ur one s 1 in c hlo ro fo rm a t r oom te m pe r a tur e .
Nit r ili mi ne de r iva ti ve s we r e ge ne r at ed in situ f r om the
a- ch lor oa r yl ide ne phe nyl hyd ra z one s un der th e a c tion
Na S O a n d th e so l ve nt was r emo ve d un d er v ac uu m.
2
4
Th e c ru d e p ro d u ct was cr ys t al li ze d i n et h an ol a nd th e
s o l id o b ta i n e d wa s fil t er ed an d u sed .
2
. 2 f Synthesis of pyrazole-bearing sulfonamide of tr i et hyla m ine . The r ea c ti on le d to th e f or ma t ion of a
moiety (6aa–6da): I n a 1 00 mL Er l en mey e r fl as k, spi r an ic c yc loa dd uc t 2 a s a uni que r eg ioi som e r w ith a
p y ri di n e (6 mL ) was ad de d t o a so l ut i on o f 5- ( 2- goo d yi el d ( Sc he m e 1) .
a m i n o b e n zo y l )p yraz ol e 3 ( 0.0 19 mo l) i n 2 m L
The r eg ioc he m ist ry pr op ose d in th is r ea c tion is
d i c hl o ro m e th a n e . Th e mi xt u re was st i rr ed un d er ic e - c om pa ra bl e to th at obs er ve d wit h si mi la r dipo -
5
2
c o l d c o n d it io n . T o sy l ch l or id e ( 0.0 19 mo l) was a dde d la r oph ile s,
b y fra c t io n s , ma in t ai ni ng t he t emp er at u re of th e 2- a r y li de n e- t e tr a l - 1( 2 H) - one s
na m el y
2- a r ylid en e- i nda n- 1- one s ,
5
3 , 5 4
a nd 3- a r ylide ne -
re a c ti o n mi x tu re up t o 0°C. W he n t he ad di t io n wa s c hr om en -4( 3H) - one s. Thi s r eg ioc he m ist r y w as a ls o
c o mp le te d , th e st i rr i ng was co nt i nu ed at r oom c he ck ed wit h H a nd C NMR spe c tr a l da ta . I nde e d,
5
3
1
1 3
1
t e m p e ra tu r e u n ti l TL C r eve al ed t he co mp let ion of
H NMR spe c tr a of c yc loa dd uc ts 2 sho wed a br oa d
t h e re a c ti o n . T h e mi xt u re was qu en ch ed i n ic e - co ld si ngle t a t 4.5 pp m e xc ha nge a ble wit h D O c or r e -
2
wa te r a n d n e u tr al i zed di l ut e HCl ( pH = 2) a nd spo ndi ng to NH pr ot on a nd a si ngle t a ro und 5 ppm due
0
e x t r a ct e d wi th DCM ( 3 x 2 0 mL ). Th e or g ani c la ye r to py ra z oli ne pr ot ons. W he r ea s, wit h a r eg ioi some r 2 ,
wa s d ri ed o v e r a nh yd ro us Na SO , t he so l ve nt wa s th e c he mi ca l shi f t of th e pyr a z oli ne pr ot ons w ould
2
4
e v a p o ra te d u n d e r r edu ce d pr es su re . Th e r esul ti ng nor m a lly be de shi el de d und er th e e ff e c t of the

8
6
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J. Chem. Sci. (2 020) 1 32: 86
Scheme 1. 1, 3- Di po la r cy cl oad di ti on rea ct ion aff ord s s pi ro p yr azol in es 2.
Scheme 2. S yn th e ti c pa th wa y of 5- (2- am i nob enz oyl ) -3, 4 -d iar yl -1 -p hen yl pyr azo l es 3.
13
n e i gh b o rin g n it ro g en at o m. Fu rt h er , C NM R spe c tr a 3( 2H) - one f r am e wor ks a nd le a ds to th e f or ma tio n of
s h o we d c h e mi c a l sh i ft ar ou nd 8 7 pp m as si gn ed to 5- ( 2- a mi nobe nz oyl )- 3, 4- dia r yl- 1 -p he nyl pyr a zo le s
3
5
5
s p i r a n ic c a rb o n C 52
c h e mi c a l s h if t v a l ue s sh ou l d be ex pe ct ed f or th e spi -
ra n ic c a rb o n C 4 2
. Th es e ou t co me s co rr o bo ra te f ur the r li she d by spe c tr os cop ic da ta ( FT -I R , H a nd
t h e p ro p o s e d re gi o ch emi s t ry . I n ad di t i on , F T–I R
s p e c tra o f th e c y cl o ad du ct s 2 r eve al ed , i n p ar t ic ula r , e xhi bit ed two c ha ra c te r ist ic ba nds r an gin g be tw e en
0
; f or t he r egi o is om er 2’ lo wer wit h goo d yi el d ( Sc he m e 2) .
The c he mi ca l st ru ct ur es of py ra z ole s 3 we r e e st a b-
1
0
1
3
C NMR ) . I nde e d, F T- IR spe c tr a of c om po unds 3
-1 ,
t h e p re s e n c e o f ab so rp t io n ba nd s at t ri b ut ed a ro und 320 0 a nd 34 20 c m
3 0 0 c m a n d 1 70 0 cm , r esp ec ti v el y, t o N –H a nd
C =O s tr et c h in g b and s wh il e t he ab so rp t io n ba nd a t
1 wa s as si g ne d t o C= N st r et ch i ng ba nds
b e ca u s e o f ri n g c lo su re .
in dic a tin g th e pr e se nc e of a
pr im a r y a mi ne NH gr ou p. Abso r ptio n ba nd a r ound
16 00 c m wa s a ssi gne d to C =O st re tc hi ng ba nd,
whi ch a ppe a r le ss th an th at obs er ve d on c yc loa dduc ts 2
-1
-1
3
2
-1
-
1
6 0 0 c m
1
spe c tr a . The H NMR spe c tr a of c om poun ds 3 s howe d
in a ddi tio n to si gna ls c or r esp ondi ng to a ro ma tic pr o-
to ns, a br oa d si gna l a t 6.3 ppm a ssi gne d to NH pr o-
2
1
3
to ns. The i r C NMR spe c tr a di spla ye d a si gna l a t 189
ppm a ssi gne d to C =O c ar bo n 10 ppm shi e lde d , c om-
pa r ed wit h th e on e obs er ve d on th e spe c tr a of the
c or r esp ondi ng c yc loa dd uc t 2. I n a ddi tio n, th e dis a p-
3 . 2 Synthesis of 5-(2-aminobenzoyl)-3,4-diaryl-1-
phenylpyrazoles (3)
Th e p re p a re d s p i ro py ra zo li n es 2 wer e t re at e d wit h pe a re d si gna ls a t 5 pp m ( pyr a zo lin e pr ot on) a nd 87
1
1 3
c o n c e n tra t e d h y d ro chl o ri c ac i d i n et h an ol at r efl ux . pp m ( spi ra ni c c ar bo n) , r es pe ct ive ly , in H and
C
Th e re a c ti o n u n de rg oe s r in g- op en i ng of t he s pir a nic NMR spe c tr a of c om poun ds 3 pr ov ide d th e e vide nc e
c y c lo a d d u c t s a t t he ni t r og en at o m of t he i ndo lin - f or th e r ing -o pe nin g of spi r an ic c yc loa dd uc ts 2.

J. Chem. Sci. (2 0 2 0 ) 13 2: 86
P age 5 of 8 86
Scheme 3. S y nt het i c ro ut e of pyr azol e der iv at i ves .
Table 1. P h ys i cal an d MS da ta of t he s ynt hes i zed pyr az ol es .
0
En t r y
A r
A r
C H
Ti m e (h ) m . p. ( °C ) Yi el d (% ) HR MS (m / z*)
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
6
6
6
6
6
6
6
aa
ab
ba
bb
ca
cb
da
db
aa
ab
ba
bb
ca
cb
da
db
aa
ab
ba
bb
ca
cb
da
C H
6
C H
6
1 0
1 2
2 0
1 5
8
162 –164
186 –188
112 –114
140 –142
198 –200
214 –216
168 –170
224 –226
170 –172
196 –198
184 –186
216 –218
180 –182
212 –214
190 –192
202 –204
180 –182
172 –174
188 –190
182 –184
196 –198
208 –210
200 –202
84
67
59
60
72
61
55
70
61
53
66
70
58
77
72
81
60
54
76
66
80
71
74
542 .1 832
576 .1 439
572 .1 930
606 .1 538
576 .1 437
610 .1 058
620 .0 931
654 .0 544
480 .1 680
514 .1 284
510 .1 774
544 .1 383
544 .1 279
548 .0 891
558 .0 777
592 .0 387
592 .1 663 5
626 .1 272
622 .1 756
656 .1 364
626 .1 262
660 .0 869
670 .0 757
5
5
6
5
4- ( Cl ) C H
6
5
5
5
5
5
5
5
5
5
5
5
4- ( OC H ) C H
3
4- ( OC H ) C H
3
4- ( Cl )C H
6
4- ( Cl )C H
6
4- ( Br )C H
6
4- ( Br )C H
6
C H
6 5
6
5
4- ( Cl ) C H
6
6
5
C H
6 5
5
5
4- ( Cl ) C H
6
1 1
2 4
1 8
6
3
4
7
8
6
2
4
5
9
4
8
1 0
7
C H
6 5
5
5
4- ( Cl ) C H
6
C H
6
C H
6
C H
6 5
5
5
4- ( Cl ) C H
6
4- ( OC H ) C H
3
C H
6 5
6
5
4- ( OC H ) C H
6
4- ( Cl ) C H
6
3
5
4- ( Cl )C H
6
4- ( Cl )C H
6
4- ( Br )C H
6
4- ( Br )C H
6
C H
6 5
5
5
4- ( Cl ) C H
6
C H
6 5
5
5
4- ( Cl ) C H
6
C H
6
C H
6
C H
6 5
5
5
4- ( Cl ) C H
6
4- ( OC H ) C H
6
C H
6 5
3
5
4- ( OC H ) C H
3
4- ( Cl )C H
6
4- ( Cl )C H
6
4- ( Br )C H
6
4- ( Cl ) C H
6
6
5
C H
6 5
5
5
4- ( Cl ) C H
6
C H
6
5
5
5
?
*
M as s ob ta in ed f or [ M ?N a] io n.
3 . 3 Synthesis of pyrazoles bearing amide
and sulfonamide
ph eny lpy ra z oles 3 on tr e a tin g wit h be nz oyl c hlo-
r ide , a ce ti c a nhyd ri de a nd pa r a- t olue ne sul fo nyl
c hlo ri de f or me d th e r eq uir e d pyr a z ole de r i va tive s
c ont ai ning a mi de a nd sul f ona m ide sc a ff ol d, w hic h
a re kn own f or th ei r bi olog ic a l a c tivit ie s
Th e s y n th e ti c p a t hwa y f ol l owed f or t he p repa r a tio n
o f n o v e l p y ra z ol e d eri v at iv es i s i ll u st rat ed in
Sc h em e 3. T h e 5 -( 2- am in ob en zoyl ) -3 ,4 -d ia r yl- 1 -
1
8 ,1 9 ,2 2
(
Sc he m e 3 ) .

8
6
Pa g e 6 o f 8
J. Chem. Sci. (2 020) 1 32: 86
Th e s tr u c tu re s of co mp ou nd s 4, 5 an d 6 we r e Acknowledgements
1
13
c o n fi rme d b y F T-I R, H NM R, C NM R and m as s
s p e c tro me t ry a n al y si s. Th e FT –I R sp ec tr a of c om -
p o u n d s 4, 5 a n d 6, i n pa rt i cu l ar , sh owe d t he pr e se nc e
The aut ho rs are gr ate ful t o ‘‘C i t e´ de l ’In nova t io n’’ o f Si d i
Moh am ed B en Ab de l la h Un ive r s i ty fo r s pec tr o sc o pi c
m eas ur em en t. Thi s wo rk has bee n s upp or t ed b y t he
C ES AMO pl at fo rm (B or de aux Un ive r s i ty ).
-
1
o f a b s o rp ti o n b a n ds ar ou nd 33 0 0 cm co rr es pon d to
N– H b o n d s tr et c h i ng . Two ab so rp t io n ba nd s a ro und
-1
-1
7 0 0 c m a n d 1 600 cm i nd ic at e t he pr es e nc e of
1
C =O s tr et c h in g s o f ca rb ox am id e an d c ar bo nyl
1
g ro u p s , re s p e c tiv e l y. Th ei r H NM R sp ec tr a re ve a le d
References
a s i n g le t a t a ra ng e of 9– 1 2 pp m ex ch an ge ab le wit h
D O c o rre s p o n d in g t o NH pr o to n. Two si n gle t s a t
2
1. Kh an M F , Al am M M, Ver m a G, Ak hta r W, Ak ht e r M
and S haq ui quz zam a n M 201 6 The t hera pe ut i c voy ag e o f
pyr azol e and i ts ana lo gs : A rev ie w Eur. J. Med. Chem.
2
re s p e c tiv e l y , o f a ce ta mi de f or co mp ou nd s 5 an d to syl
. 2 5 p p m a n d 2. 44 p pm r el at ed t o CH pr ot ons,
3
13
120 1 7 0
fo r c o mp o u n d s 6. Th e C NM R sp ec tr a o f t he sa m e
c o mp o u n d s e x h ib it e d a si g na l at 1 66 pp m at tr ibu te d
t o C= O c a rb o n o f ca rb ox am id e f or co mp ou nd s 4 a nd
2
. K K u¨ c¸ u¨ kg u¨ z e l S¸ G an d S¸ e nk ar de s¸ S 2 01 5 Re c e nt a d van ces
in b io a c tiv e p y r a zo le s Eur. J. Med. Chem. 97 786
. Gar c ´ı a-V ane gas J J , R am ´ı rez -Vi l la l va A, F uen t e s- Be n-
i te s A, Mar t ´ı nez - Ot er o D, Go nz a´ l ez-R i v as N a nd
C uevas - Ya n˜ ez E 201 9 S ynt he s i s and i n-v it ro bio l o gi c al
eva lu at i on of 1, 1-d iar yl -2 -( 1, 2, 3)t ri az ol -1 -yl - e t ha n ol
der iv ati v es as ant i fu nga l com p ound s fl ut ri af ol a na -
l ogue s J. Chem. Sci. 131 27
3
5
a s we ll a s a s ig na l at 19 2 p pm co rr es po n din g to
C =O c a rb o n o f ke t on e. I n ad di t i on , t he si gna ls
b e t w ee n 2 1 a n d 2 5 pp m wer e as si g ne d t o m et hyl
c ar b o n CH fo r co mp ou nd s 5 an d 6. Ab ou t hi gh-
3
re s o lu tio n ma s s sp ec tr o met r y, sp ec tr a i n p osi tiv e
m o de h a v e b e e n r eco rd ed wi th an el e ct ro sp r ay io n-
?
i z at io n c h a mb e r wh ic h l ed t o [ M ?Na] ad du c ts. All
4
. Yad av P and P uro hi t N V 201 3 S ynt he s i s and eva l ua t i on
of s om e bi oa ct i ve com p o und s hav i ng oxy ge n a nd
ni t roge n het er oa t om J. Chem. Sci. 125 165
fir s t mo l e c u la r ma ss p eak s wer e cl o se t o t h e th eo -
re t i c a l v a lu e (Dm ass pe ak \ 3 ppm ). Fi n al ly , spe c tr o-
s c o p ic d a ta we re f ou nd t o b e i n g ood ag re em en t wit h
t h e p ro p o s e d s tr uc tu re s ( Tab l e 1) .
5. S hah N K, S h ah N M, P at e l M P and P at el R G 2 01 3
S ynt he s i s of 2- am in o-4H -ch rom ene der i vat i ves u nd er
m i crow a ve i rra dia t i on and t hei r ant i m ic ro bi al act i vi t y J.
Chem. Sci. 125 525
6
. J eya veer an J C , P rav e en C , Ar un Y, P ri nce A A M a nd
P eru ma l P T 201 6 C ycl oi s om eri za ti on of ac et y l e ni c
oxi m es and hyd razo nes und er gol d cat al ys i s : Sy n t he si s
and cyt o t oxi c eva lu ati on of i s oxazo l es and pyr az o l e s J.
Chem. Sci. 128 73
4
. Conclusion
7. B urs ch ka J , Du a l eh A, Kes s l er F , B aran off E, C ev ey - Ha
N L, Yi C , Naz eer udd in M K and Gr a t zel M 2 01 1
¨
In th i s s tu d y , we p rep ar ed no v el p yr azo l e d eri v a tive s-
b e a rin g a mi d e an d su l fo na mi de mo ie t ie s th ro ugh
re s p e c tiv e 1 , 3- d ipo l ar cy cl o ad di ti o n an d N- al k yla ti on
re a c ti o n s . W e h ave sh own t ha t t he 1, 3-d ipol ar
c y c lo a d d i ti o n re a ct i on s oc cu r i n a r egi o sp eci fi c m an -
n e r a n d c o n d u c t to on e r egi o is om er 2 i n ea ch st udie d
c as e . T h e s p ir o p yr az ol i ne 2 ar e de ve l op ed i nt o pyr a -
z o l e- co n t a in i n g 2 - ami no be nz oy le f ra mewo rk s, whi ch
a re e n g a g e d in N- al ky la ti o n r eac t io ns t hr ou gh th e
a m i n o g ro u p . T h e st r uc tu re s an d r egi o ch emi s t ry of th e
c y c lo a d d u c t s a n d ot h er ob t ai ne d p ro du ct s wer e ju sti -
Tri s (2 - (1 H-py razo l -1- yl )pyr i di ne) cob alt (I I I) as p -T yp e
dop ant fo r or gani c s em i cond uct or s and i ts app li c at i o n i n
hi ghl y effi c ien t s ol i d- s t at e dye -s ens i t iz ed s ol ar c el l s J.
Am. Chem. Soc. 133 180 42
. Gi or na l F , P azen o k S , R od efe ld L, Lui N, Vor s J a nd
Ler oux F R 201 3 S y nt hes i s of di ver s ely fl u or i n at e d
pyr azol e s as nov el act i ve agr ochem i cal i ngr edi e nt s J.
Fluor. Chem. 152 2
. R om ero A, R am os E, Ar es I, C a s t el lan o V, Mar t i ne z M,
Mar ti ınez -L arr anag a M R , An adon A and Mar ti n ez M A
201 6 F i pron il s ul fo ne i nduc ed hi ghe r cyt o t oxi c it y t ha n
fi pro ni l i n S H-S Y 5Y cel l s : pr ot ecti o n by ant i ox i d an t s
Toxicol. Lett. 252 42
8
9
1
fie d b y s p e c tro s c op i c t ec hn iq ue s, viz., I R, H NMR ,
1
3
10. Has s a n A S , Mou s t afa G O, As k ar A A, Nag la h A M
and Al -O m ar M A 201 8 S yn t hes i s and ant i b ac t er i a l
eva lu at i on of fu s ed pyr azol e s and S chi f f bas es Synth.
Commun. 48 276 1
C NM R a n d HR- ma ss . Th e st r uc tu re s of al l syn -
t h e s iz e d p ro d u c ts ar e i n pe rf ec t ag re em ent wi th spe c -
t ro s c o p ic d a ta .
1
1. C hauha n S , P al iw al S and C hau han R 201 4 An t ic a nc er
act i vi t y of pyr azol e vi a di ff erent bi ol ogi cal m ec ha ni sm s
Synth. Commun. 44 133 3
Supplementary Information (SI)
1
S p ec tr o s c o pi c d a ta an d co pi es of s pe ct r a ( IR , H N M R ,
1 3
C
12. Des h m ukh S , Di ngo re K, Gai kw ad V and J ac ha k M
01 6 An effi c ien t s ynt hes i s of pyr az ol o[ 1,5 - a]py r im i d i-
2
NM R , a n d HR -m a s s ) of al l ob ta in ed co m po un d s a re g i ven
i n t h e s u p p l e me n t a r y in f or m at io n, w hic h ar e av a i l abl e at
ww w .i a s .a c. i n/ c h em s ci .
nes and eva lu ati on of t hei r ant i m ic robi al act i vi t y J.
Chem. Sci. 128 145 9

J. Chem. Sci. (2 0 2 0 ) 13 2: 86
P age 7 of 8 86
1
3 . Pa rs h a d M , Ve rm a V , K um ar D , N ar as im ha n B, Ko ur S ,
Si n g h S a n d Sa ng w an P L 20 15 I od ob enz en e d ia c et at e-
m ed i a t ed i s o me ri z at io n of py r azo ly l ch al con e s and t hei r 28. C arr as co M P , Mac h ado M, Go n c¸ al ve s L, S har ma M,
s ynthes is , and biological act ivity on bladder car ci no ma
cel l l ines Bioorg. Med. Chem. Lett. 17 208
c y to t o x i ci t y a n d an ti -m i cr ob ia l ac tiv i ty J. Chem. Sci.
27 4 1 3
4 . Fa i s al M , Sa e ed A , H us s ai n S , D ar P an d Lar ik F A
0 1 9 R ec en t d e ve lop m en ts in s yn t he ti c ch em is t ry and
Gu t J , Lu ken s A K, Wi rt h D F , An dr e´ V, Du art e M T ,
Gu edes R C , dos S ant os D J V A, R os ent ha l P J,
Maz it s che k R , P rud eˆ nci o M and Mor ei ra R 2 01 6
P rob in g t he Aza aur one S caf fo l d aga in st t he He pa t i c
and Ery th roc yt i c S t age s of Mal ar ia P ara s i te s Chem.
Med. Chem. 11 219 4
1
1
1
2
b i o l o gi c al a ct i v it ies of py r azo le de ri va t iv es J. Chem.
Sci. 131 7 0
5 . Sw am i S, Ag a rwa la A , Ma li k B an d S hr iv as ta va R 201 6 29. S har ma M C , S h arm a S , S har ma P and Ku ma r A 2 01 4
A n e w c la s s o f ef fi cie nt 4- [ ( nit ro s ub s tit ut ed- phe nyl )-
h y d ra zo n o m e th y l] - 1- ph eny l - 1H -p yr az o le -3 - c ar b oxyl a t e
d e ri ve d c o lo ri m et ri c ch em os e ns o r f or s el ec tiv e s ens i ng
P har ma c oph ore and QS AR m ode l in g of s om e st r u c-
t ural l y di ve rs e azaa ur one s der iv ati v es as ant i - ma l a ri a l
act i vi t y Med. Chem. Res. 23 181
o f flu o r id e a n d o th er bi ol og i ca lly im p or ta nt ani on s J. 30. Zhan g M, Li T, Qi an M, Li K, Qi n Y, Zhao T an d Ya ng
Chem. Sci. 128 14 51
6 . B l ai r L M a n d S pe rr y J 20 13 N atu r al pr oduct s
L. -Q 201 8 S y nt hes i s and B io l ogi cal Act i v it i e s o f
1- Azaa ur one Der iv ati ve s J. Heterocycl. Chem. 55 1 57 4
c o nt a i n i n g a n i tr og e n- n itr o gen bo nd J. Nat. Prod. 76 31. S oua rd F , Ok om bi S , B eney C , C heval l ey S , Va l en t i n A
1
1
7
9 4
and B ou m end jel A 201 0 1- Azaa ur ones der iv ed fr om t he
nat ur al ly occ urri ng aur on es as pot en ti al ant i ma l a ri a l
dr ugs Bioorg. Med. Chem. 18 572 4
7 . Ku m ar V, Ka u r K , G up ta G K an d S ha rm a A K 201 3
Py r az o l e c o nt a i n in g na tu ra l pr o du c ts : S yn th e ti c pr evi ew
a n d b i o l o gi c al s ig n ifi ca nc e Eur. J. Med. Chem. 69 32. C am pa ni c¸ o A, C arr as co M P , Nj or og e M, S el d o n R,
7
3 5 – 7 5 3
8 . Ha s s an G S, Ab ou - Se r i S M, K am el G an d Al i M M
0 1 4 C el e co x i b an al og s be ar in g be nz of ur an mo ie t y as
c y cl o o x y g e n a se - 2 in hi bi tor s : D es ig n , s yn t hes i s and
C hi bal e K, P erd ig a˜ o J , P ort ug al I, Wa rner D F , Mo re i r a
R and Lo pes F 201 9 Aza aur one s as pot en t a nt i my -
cob act er i al age nt s act i ve aga in s t MDR - and XDR - TB
Chem. Med. Chem. 14 153 7
1
1
2
e v al u a t i o n a sp o t en ti al an ti -i nfl a m ma to r y ag en t s Eur. 33. B ough al eb A, Zou ihr i H, Gm o uh S , Ker bal A a nd E l
0 0
Yaz id i M 201 1 (2 RS , 4 R S )-3 -( 3-C hl o ro -4- m e th o xy -
J. Med. Chem. 76 48 2
0
0
0
9 . C o x S K, R o a rk J , G as s el A an d To bi a s K 200 5
De t er mi n at i o n o f de ra co xi b in f eli ne pl as m a s am pl es
u s i n g h i g h p e rf or m an ce li qu id ch ro m at og r aph y J.
phe nyl )- 4 -p hen yl -4 H- s pi ro -[i nde ne- 2, 5 -i s oxa z o l] -
1( 3H)- one et ha nol m ono s ol vat e Acta Crystallogr. Sect.
E Struct. Reports Online 67 o24 34.
Chromatogr. B Anal. Technol. Biomed. Life Sci. 819 34. Zhan g L J , Wa ng Y, Hu X Q and Xu P F 2 01 6
1
8 1
Hy drog en -B on di ng Net w or k P rom ot ed [3 ?2] C yc l o ad -
di t io n: as ym m et ri c cat al yt ic con s tr uct io n of s pi r o- p se u -
doi nd o xyl Der iv ati ve s Chem. An Asian J. 11 83 4
2
2
0 . B o u s ta n y -Ka ri C M, J ac ks on V M, G ibb on s C P and
Sw i ck A G 2 0 11 Lep ti n po te nt ia tes th e an ti- o bes i t y
e ffe ct s o f ri m o na ba nt Eur. J. Pharmacol. 658 270
1 . Gi a n ca rl o G M , V en ka ta kr is hn a n K , G ra nd a B W, Vo n
M o l tk e L L a n d G re enb la t t D J 2 00 1 Re lat i ve con tr i-
35. Dai s l ey R W, El agb ar Z A and Wa lk er J 198 2 R ea c ti o n
of i ndol -3 (2H) -on e der iv ati v es wi t h s om e a ct i ve
m et hyl ene com p ound s J. Heterocycl. Chem. 19 1 01 3
b u t i o ns o f C YP2 C 9 an d 2 C1 9 to ph en yt oi n 4- hydr ox- 36. Yan g L, Hu a ng W, He X H, Yan g M C , Li X , He G,
y l at i o n i n v it ro : I nh ibi ti on by s ul f aphe naz ole ,
o m ep r az o l e, a n d ti cl op id in e Eur. J. Clin. Pharmacol.
P eng C and Han B 201 6 S t ereos e l ect iv e s ynt h es i s o f
Hy drop yr ano [3 , 2-b] in d ol es vi a Or gan ocat a l yt ic As y m-
m et ri c In vers e- El ect ron -D em an d Ox a-D i els –A ld e r
R eact io n Adv. Synth. Catal. 358 297 0
5
2 . W yd e P R , Gi lb er t B E an d A m br o s e M W 198 9
7 3 1
2
2
C o mp a ri s o n o f th e an ti -r es p ir at or y s yn cy ti a l vi ru s 37. Wa ng M, R ong Z Q and Zhao Y 201 4 S t ereos e l ec t i ve
a ct i v i t y a n d t o xi ci ty of pa pa ve r in e hy d r och lo ri de and
p y ra zo f u r i n i n vi tr o an d in vi vo Antiviral Res. 11 15
3 . Ts u t o m u K a n d To s hit ak a N 19 78 Ef fe ct s of 1, 3-
d i p h en y l -5 - (2 -d im e thy la m in op r op io na m id e) - Pyr a-
z o le [d i fe n a mi z o le ] on a co nd i ti on ed av oi da nc e res p ons e
Neuropharmacology 17 24 9
s ynt hes i s of e-l act o nes or s pi ro -h et ero cy cl es t hr o ug h
NH C- ca t al yzed ann ul at i on: Di ver gen t rea ct i vi t y b y
cat al ys t con t ro l Chem. Commun. 50 153 09
38. Gu o C , S ched l er M, Dan il i uc C G, Gl or ius F 2 01 4
N- het eroc ycl i c car bene cat al yzed fo rm al [3 ?2] a nn ul a -
t io n rea ct io n of ena ls : An effi c i ent ena nt i ose l ec t i ve
acce s s t o s pi ro -h et ero cy cl es Angew. Chem. Int. Ed. 53
102 32
2
4 . Fu s t e ro S, An t on io S F an d S anz - Ce rv er a J F 200 9
R ec en t a d va n c es in th e s yn th es i s of py r az ol es . A rev i ew
Org. Prep. Proced. Int. 41 25 3
39. B ir ch A J and Wr ig ht J J 19 69 The br evi ana m i de s : A
new cl as s of fu ngal al ka l oi d J. Chem. Soc. D 6 44 b
Fu e n t es A 2 0 1 1 F ro m 2 00 0 to m id -2 0 10 : A fr ui t fu l 40. P at ers on R R M, S i m m ond s M J S , Kem m el m ei er C a nd
2
5 . Fu s t e ro S, S a´ n ch ez - Ro se ll o´ M, Ba rr io P an d S i m o´ n-
d e ca d e fo r t h e s yn t he s is of py r az ol es Chem. Rev. 111
9 8 4
6 . Sh a wa l i A S 20 14 Ch e m os e lec t iv it y in 1, 3 -Di pol ar
C y cl o a d d i t io n Re act ion s of N i tr il im in es w ith Mul t i -
fu n c ti o n a li z e d D ipo la ro p hi le s Curr. Org. Chem. 18 598
B la ney W M 1 990 Eff e ct s of br evi ana m i de A, i t s
pho to ly s i s pr oduc t br evi ana m i de D, and och rat o x i n A
fr om t wo P en i ci ll i um s t rai ns on t he i ns e ct p es t s
S pod opt era fr ugi pe rd a and Hel i ot hi s vi res c ens Mycol.
Res. 94 538
6
2
2
7 . Gerby B , Bo um endjel A , Blanc M, Bringuier P P , 41. Wi l l ia m s R M, Gl i nk a T, Kw as t E, C off ma n H a nd St i l l e
C h am p e lo v i er P , F o r t un e´ A , Ronot X and Boutonnat J
00 7 2 -Arylidenedihydr oindole-3-ones: Des ign,
J K 1 990 As ym m e t ri c, s t ereo c ont r oll ed t ot al s yn t he si s o f
(- )-b revi ana m id e B J. Am. Chem. Soc. 112 808
2

8
6
Pa g e 8 o f 8
J. Chem. Sci. (2 020) 1 32: 86
4
2 . Pe a rs o n W H, L ee I Y , Mi Y an d S to y P 20 0 4 Tot al 49. Bakhouch M, El Yazidi M, Al Houari G, Saadi M a nd El
0
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0
0
s y n t he s i s o f t h e K op s ia la pi dil e ct a al kal oi d ( ± )- la -
p i d i le c t i n e B J. Org. Chem. 69 91 09
3 . J i Y, He X, Pe n g C an d H uan g W 20 19 Re cen t a dvan ces 50. R o¨ s s i n g A 188 4 B eobac h t unge n u¨ ber i nne re C on d en sa -
Amm ari L 2018 3 , 4 -Di phenyl -3H, 4 H-s pi ro[b en zo [b ]
0
4
4
i n t h e s y n t he s is of C2 - sp ir op s eu do ind o xy l s Org.
t io nen bei Ab k o¨ m m l in ge n des S al ic yla l deh yds Berichte
Biomol. Chem. 17 28 50 der Dtsch. Chem. Gesellschaft 17 298 8–30 1 0
4 . B o u gh a l e b A, A l H ou a r i G , Be nn ani B, D aoud i M, 51. R odr ´ı g uez -Dom ´ı ngu ez J C , B al buzan o- Deu s A, L o´ p ez -
Ga rri g u e s B , K er bal A an d El Y azi di M 201 0
C y cl o a d d i t io n d es N -p h e´ ny l- C - ar yln it r ili m in es s ur des
d e´ ri v e´ s d e l a 2 - ben zy li d e` n eb en zo[ b] ti op h e` n- 3 (2H )-o n e
L o´ pez M A and Ki rs c h G 200 7 An i m prov ed s y nt h es i s
of 1- ac et yl -1H - i ndol -3 -yl acet at es J. Heterocycl. Chem.
44 27 3
(
t h i o au ro n e s ) J. la Soci e´ t e´ Chim. Tunisie 12 10 9
52. Ker bal A, Ts hi a m al a K, Veb rel J and Laud e B 1 98 8
C ycl oa ddi t i on de que l que s di ary l ni t ri li m i ne s su r
di ver s e s ary l i dene- 2-i n dan one s -1 . R e gi o- et d ia s te r e-
och im i es des s pi r opy razo l i nes s ynt h e´ t is e´ es Bull. Soc.
Chim. Belg. 97 149
53. L e´ vai A 200 2 S ynt he s i s of 2 -p yrazo li n es b y t he
rea ct ion s of a, b-u ns a t urat ed al dehy des , ket o n es , a nd
es t ers wi t h di az oal kan es , ni t ri l e i m in es , and hy dr a z in e s
J. Heterocycl. Chem. 39 1
54. Ker bal A, Ts hi a m al a K, Veb rel J , Laud e B and Me rc i er
M F 199 1 R e´ act i on de di ary ln it rl i m i nes su r d es
2- aryl i den e-t et ral i n-1 -o nes s ubs t i tu e´ es . In flu en c e d es
fac te urs con form at i onnel s s ur l a di as t e´ reo chi m i e d e l a
r e´ act i on Bull. Soc. Chim. Belg. 100 159
4
5 . B o u gh a l e b A, A kh azza ne M, A l H ou ari G , D ao udi M,
Ga rri g u e s B , K er bal A an d El Y azi di M 201 1
C y cl o a d d i t io n d es ar yl ni tr il ox yd es s ur de s d e´ ri v e´ s d e
l a 2 -b e n zy l i d e` ne be nz o[ b ]t hi oph e` n- 3 ( 2H ) - on e (t hi oau -
ro n e s ) J. la Soci e´ t e´ Chim. Tunisie 13 11 7
4
4
4
6 . M ah f o u d A, Al H ou ari G , El Y azi di M, S aad i M and El
0
0
Am m a ri L 2 0 1 5 Cr y st al s tr u ctu r e of 3, 4 - di ph enyl -3 -
0
0
p -t o l y l -4 H -s pir o [i n da n- 2 ,5 - [1 ,2 ]o xa zo l] - 1- o ne Acta
Crystallogr. Sect. E Crystallogr. Commun. 71 o8 73
7 . B ak h o u c h M , Al H ou a r i G , D aou di M, K er bal A and El
Ya zi d i M 2 0 1 5 Mi ch ael ad di ti on of ac tiv e m et hyl ene
c o mp o u n d s t o (Z) - 2- a r yl ide ne ben zo [b ] th io ph en -3 (2H) -
o n es Mediterr. J. Chem. 4 9
8 . B ak h o u c h M , E l Y azi di M, A l H ou a r i G , S aad i M and 55. Dao u B , S oufi aou i M and C arr i e´ R 198 9 R e´ gi os p e´ c ifi ci t e´
El Am m a ri L 20 17 3 - (4 - C hl or o phe n yl ) -4 -p hen yl -
0
H,4 H-s p i ro [ b en zo [b ]t hi op he ne - 2,5 - is ox az ol ] -3- one
0
de l a cyc lo addi t io n des di ar yl ni t ri li m i nes s ur q ue l qu e s
d e´ ri v e´ s i ndol i que s J. Heterocycl. Chem. 26 14 85
0
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