A mechanistic insight into the acid catalyzed, one-pot synthesis of isoindole-fused quinazolin 4-ones

Article abstract of DOI:10.1007/s12039-020-01768-3

Abstract: One-pot synthesis of isoindole fused quinazolin 4-ones via intramolecular 1,3 hydride transfer in the presence of acid catalyst has been described. Substrate scope and mechanistic insights were investigated. Substituents on the amide side have a negligible influence on the key step and therefore the method have wide scope for accessing various bicyclic core structure. Graphic abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s12039-020-01768-3

J. Chem. Sci. (2 0 2 0 ) 13 2: 63
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REGULAR ARTICLE
A mechanistic insight into the acid catalyzed, one-pot synthesis
of isoindole-fused quinazolin 4-ones
*
M OHA BUL A M ONDAL , SUD IP TA MOND AL a nd AB DUL A KHAN
De p ar t m en t of Ch e m is t ry , J ad av pu r Un i ver s it y, Ko lka ta 700 032 , We s t B engal , In di a
E- ma i l: m oh a bu la .m o nd al @ ja dav pu r uni ve rs i t y. in
MS r ecei v ed 2 0 J u ne 2 01 9 ; r ev i s ed 2 2 No v em b er 2 0 1 9; accep t ed 2 J an u ar y 2 0 2 0
Abstract. O ne - po t s yn t he s is of is o in dol e fu s e d qui na zol i n 4- ones via i nt ram ol ecu lar 1, 3 hyd ri de t ran sf e r i n
t h e p res e nce of ac id ca tal ys t ha s be en des c r i bed. S ubs t rat e s cop e and m ech ani s t i c i ns i ght s wer e i nve st i g at e d.
Su b s t it ue nts on th e am i de s id e ha ve a neg li gi bl e i nfl ue nce on t he key s t ep and t here f or e t he m et ho d ha ve wi d e
s co p e f or ac ce s s in g va ri ou s bi cy cl ic cor e s t ruct u re.
Keywords. H ete ro cy c li c ch em is tr y; 1, 3-H ydr i de t rans f er; Mec h ani s t ic s t ud y; Is o ind ol e -f u se d
q u i n a zol in on es .
5
ph a rm a c eu ti ca l s a nd bi oa c ti ve m ole c u le s a nd a va il-
1
. Introduction
6– 8
a ble m et hods a re m ult ist ep in na tu re . F ur the r s tudy
of th e on e- pot m et hod ( Sc he m e 1 ) is ne c e ss a r y.
He r ei n, we wis h to r ep or t th e syn the si s of c om po und 3
wit h di ff e r en t sub sti tue nts on th e a mi de si de a nd
m ec ha ni sti c in sigh ts f or th e m et hod pr e se nt ed in
S ch em e 1 .
Qu i n az o li n o n e s a re i mpo r ta nt n it r og eno us he t er oc yc li c
c o mp o u n d s p re s en t i n ma ny b io ac ti ve n at ur a l pr od -
1
u c t s, p h a rma c e u t ic al s. I t i s pr es en t as a bu i ld i ng bl oc k
i n ma n y d ru g s in ac t iv e us e. Be cau se of t he r ic h hi s-
t o r y o f q u in a z o li n 4- o nes , i t i s a pr i vi l eg ed pha r m a-
c o p h o re to th e sy nt h et ic ch em is ts . M os t com m on
s y n th e s is o f th e s i mpl e st me mbe r 2 , 3 -d ih yd r oqui na -
z o l i n -4 (1H)-o n e in v ol ve s co nd en sa ti o n o f al d ehy de or 2. Experimental Methods
k e t on e wi th a n th r an il am i de or o th er 1, 5- N-b i snuc l e-
2
.1 General information
o p h il e ( 1). W h il e a co ns i der ab l e n umb er of r ep or ts
i n v o lv i n g re a c ti o n s of mo no al de h yd e wi th an th ra ni l-
a m id e a re a v a il a b le , t he r eac t io n of di a ld eh yde wit h
a n t h ra n il am i d e is r el at i ve ly l es s. On ly a f ew ex a mp le s
C omm e r ci al ly a va ila bl e r ea ge nt s we r e use d w ithout
f ur the r pu ri fic a tio n. All th e r ea c ti ons we r e c ar ri e d out
a t ope n ve sse l a nd m onit or e d by TLC ( TLC S ilic a G el
60 F 254) a nd it wa s ob ser ve d und er UV li gh t ( 254
nm ) . Yie ld s r ef e r to th e is ola te d pr od uct a s m enti one d
in th e e xpe r im en ta l se c tio n. NMR s we r e r ec o r de d in
B ru ke r 40 0 or 300 MHz spe c tr om e te r in DM S O- d6
sol uti on. C he mi ca l shi f ts a re gi ve n in d r el ati ve to
TM S, th e c oupl ing c onst an ts J a re gi ve n in Hz. H igh-
r es olu tio n m as s spe c tr a we r e r ec or de d on ESI - TO F
m as s spe c tr om e tr y. LC MS ta ke n usi ng ZOR BA X EX T
2
wh er e d ia l d e h d y e su ch as f ur an -3 ,4- di c ar bal de hy de,
3
t e rep h t h al a ld e h y d e, gl y ox al ar e co up l ed to gi ve
d e s ir ed d im e ric 2, 3- di hy dr o qu i nazo l in -4 ( 1H) - one s.
Th e s y n th e s is o f sy mme t ri c di me r 2 ,2’ -( 1, 2- phe ny le -
n e )b is (2 , 3 -d i h yd ro q ui na zo li n -4 ( 1H) -o ne ) f ro m o- ph-
4
t h a l a ld e h y d e a n d an t hr an il am i de ha s b een de sc r ibe d.
R e l a tiv e ly fe we r nu mb er r epo r ts ar e av a ila bl e
d e s c rib in g c o n d e ns at i on of o- ph th al al de hy de wit h
2
a n t hr a n ila mi d e d er i va ti ve s t o gi v e st r uc tu r e 3.
M o re o v e r, th e me c ha ni st i c st u dy f or t he f or mat ion of
s t ru c tu re 3 is n o t es t abl i sh ed . As t he st r uc tu re 3 is a n
i m p o rta n t s tr u c tu ra l mo ti f , i t ex i st s i n m an y
( 4.6x 50 m m, 5 l) c olu mn, NH OAc ( 10 mM ) :
C AN::9 0:10 f or li qui d c hr om at ogr a m. X- r ay c r yst a l-
lo gr ap hic da ta we r e c oll ec te d f r om S MAR T (B r uke r ,
4
*
F o r co rr e sp on den ce
Electronic supplementary material: The online version of this article (https://doi.org/10.1007/s12039-020-01768-3) contains supple-
mentary material, which is available to authorized users.

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J. Chem. Sci. (2 020) 1 32: 63
Scheme 1. S yn th e s i s of i s oi ndol e- fu s ed qui na zol i n 4- one s
2
0 0 0 ), S HE LXL -2 0 18 /3 , ve rs i on 2 018 / 3’ , at 2 73K, h
Synthesis of 3-bromoisoindolo[2,1-a]quinazolin-
ra n g e (d e g ) 2 .6 18 t o 2 7.1 35 , r adi a ti on t yp e k ( Mo K a) . 5(11H)-one (3c): S am e a s de sc r ibe d f or 3aHCl. W hite
1
S oli d, Yie ld 88 %; M. p. 25 7 °C ; H- NMR ( 400 M Hz ,
DMS O-d ?C DCl ) d 8.2 1 ( s, 1H) , 8.0 2 ( d, J = 8H z,
6
3
2
. 2 Experimental procedure and spectral data
1
H) , 7.9 6–7. 93 ( m, 1H) , 7.7 6–7.6 9 ( m, 2H) , 7.62– 7.58
1
3
(
m, 2H) , 5.4 1 ( s, 2H) ; C -NM R ( DMS O- d ?C DC l )
6 3
Synthesis of 5-oxo-11, 12-dihydro-5H-isoindolo[2,1-
a]quinazolin-12-ium chloride (3aHCl): A mi xt ur e of
a n t hr a n ila mi d e (3 40 mg , 2. 50 mmo l ), an d o- pht ha -
l a ld e hy d e (3 3 4 . 9 mg , 2. 50 mmo l ) wer e t a ke n in
d: 611 .4, 149 .9, 139 .6, 137 .5, 133 .6, 131 .9, 131.6 ,
31 .5, 129 .5, 124 .5, 123 .0, 120 .1, 11 9.6, 11 6.3, 52.0;
ES I -T OF MS : C al cu la te d m as s f or C H B rNa N O i s
1
1
5
9
2
334 .979 6, obs er ve d m/z = 33 5.002 .
1
0 0 mL ro u n d bo t to m fla sk . Th en t o t hi s r ea c ti on
Synthesis of 1,3-dibromoisoindolo[2,1-a]quina-
zolin-5(11H)-one (3d): S am e a s de sc r ibe d f or 3aHCl.
m i x tu re , 3 0 mL Me OH an d 2( N) HCl ( 10 mL) we r e
a d d e d . T h is re a ct i on mi xt u re was st i rr ed a t r oom
t e m p e ra tu r e fo r 2 4 h . Th en , t he pr ec i pi ta t e app ea r e d
wa s c o ll e c te d b y fil t ra t io n an d was he d wi th wa te r to
1
W hi te S oli d, Yie ld 91% ; M. p. 25 9 °C ; H- NM R ( 400
MHz , DMS O- d ) d 8.3 7 ( d, J = 2Hz , 1H) , 8 .27 ( d,
6
J = 2Hz , 1H) , 8.0 3 ( d, J = 8Hz , 1H) , 7.8 4–7 .78 ( m,
2H) , 7.6 5 ( d, J = 8Hz , 1H) , 5.9 8 ( s, 2H) ; ESI - TO F
MS : C al cu la te d m as s f or C H B r N N aO is
1
g e t 3aHCl (4 1 1 mg , 70 %) . M .p . 25 6 °C; H- NMR
(4 0 0 M Hz , DM S O-d ) d 8. 47 ( d, J = 8 Hz, 1 H), 8.2 5( d,
6
1
5
8
2 2
J = 8 Hz , 1 H), 8 .0 6 ( dt , J = 8 Hz, 1H ), 7 .87 – 7.93 (m ,
H), 7 .7 7– 7. 6 8 (m, 2 H), 5. 71 ( s, 2H ); Ca lc ul at e d m as s
fo r C H N O is 2 35. 08 71 , o bse rv ed m/z = 23 5.032 8.
4
1 4.888 1, obs er ve d m/z = 41 4.753 .
Synthesis of 7,8,9,10-tetrahydrobenzo[4’,5’]thieno
3’,2’:5,6]pyrimido[2,1-a]isoindol-6(13H)-one (3e):
3
1
5 1 1 2
[
Synthesis of isoindolo[2,1-a]quinazolin-5(11H)-one
3a). T h e s o li d ma ss of 3aHCl ( 13 2 mg ) was tr e a te d
S ame as descr ibed for 3aHCl. White S olid, Yiel d 92%;
1
(
wi t h s a tu r at e d Na HC O so l ut i on ( 5 mL ) f or 5 m in a nd
M.p. 254 °C; H-NMR ( 400MHz , DMS O-d C D Cl ) d
6
?
3
3
7.96 ( d, J = 8Hz, 1H), 7.70–7.62 (m, 2H), 7.56 (t, J =
8Hz , 1H), 5.24 (s, 1H), 2.94 (m, 2H), 2.73 ( m, 2H ),
1.84–1.76 ( m, 4H); ES I- TOF -MS C alc ulate d mas s for
t h e n th e s u s p e n s io n was fil t er ed was he d wi th wa te r ,
d ri ed to g e t 3a (1 0 2 mg , 8 9%) as wh it e so l id . M .p. 25 8
1
°
C ; H-N MR (4 0 0 M Hz, DM SO-d ) : d 8. 14 ( s, 1H) ,
6
C H N NaOS is 317.0725, observed m/z = 31 7.0002
Synthesis of 11H-benzo[5,6][1,2,4]thiadiazino[3,4-
a]isoindole 5,5-dioxide ( 3f) : S am e a s de sc r ibe d f or
17 14 2
8
. 1 2 (d , J = 1 .2 Hz, 1H) , 8 .02 ( d, J = 8Hz ,1H) ,
. 8 9 –7 .8 5 (d t , J = 8 , 15 Hz, 1H) , 7. 82 –7 .7 4 ( m, 1H) ,
. 6 6 –7 .6 3 (m , 2 H) , 7. 51 ( t, J = 15 Hz, 1H ), 5.4 5 ( s,
H). E SI -T OF M S: Ca lc ul at e d ma ss f or C H N Na O
7
7
2
1
3
aHCl. W hi te S oli d, Yie ld 83% ; M. p. 29 5 °C ; H
15 10 2
NMR ( 400 MHz , DMS O-d ) d 7.9 2 ( dt, J = 8H z,
6
i s 2 5 7 .0 69 1, o b s er ve d m/z = 2 57. 13 72
Synthesis of 3-nitroisoindolo[2,1-a]quinazolin-
J = 12 Hz , 2H) , 7.8 1–7. 77 ( m, 3H) , 7.6 3 ( m,1H ) ,
7.5 3( m, 2H) , 5.3 8 ( s,2H) ; ES I -T OF- M S c alc ul at ed
m as s f or C H N Na OS is 293 .036 1, ob ser ve d m/
z = 29 3.122 5
5
(11H)-one (3b): Sa me as d esc ri b ed f or 3aHCl. Li ght
1
1 4 1 0 2
y e l l o w s o li d , y ie l d 8 6%; M .p . 25 2 °C; H- NMR ( 400
M Hz , DM S O- d ) d 8 .79 ( d, J = 2H z, 1H ), 8.6 4 ( d,
6
J = 2 Hz , 1 H), 8 .0 3 ( d, J = 7 .2Hz , 1H ), 7. 8 3–7. 79
(
1
m , 3 H), 7 .6 5 (t , J = 7. 2Hz , 1 H), 5. 48 ( s, 2H) ; C -
3
2.3 Experimental procedure for 3aDCl
NM R (4 0 0 M Hz , DM SO- d ?CDC l ) d 16 6 .8, 148 .5,
6
3
1
1
4 2 . 6, 1 4 1 .4 , 1 3 9 . 6, 13 1 .8, 13 0 .1, 12 7 .2, 12 6 .6, 12 2.2, A m ixt ur e of a nth ra ni la mi de ( 50 m g) a nd o- phtha -
2 2 . 1, 1 2 1 .9 , 1 1 6 .6, 1 15. 8, 5 0.7 ; ES I- TOF -M S : C al - la ld eh yde ( 49 m g) we r e ta ke n in a 50 m L r ou nd bot-
c u l at e d ma s s fo r C H N NaO i s 3 02. 05 42.0 64, to m fl as k. The n 3 m L m et ha nol -d , 0.5 m L D O a nd
9
15
3
3
4
2
o b s e rv e d m/z = 3 0 1. 94 8
0.5 m L DC l ( 20%) we r e a dde d in to th is re a c tion

J. Chem. Sci. (2 0 2 0 ) 13 2: 63
P age 3 of 5 63
m i x tu re u n d e r a rg on at mo sp he r e. Th e r eac t io n m ixt ur e sub sti tut ed a ntr a nil a mi des ( Ta ble 1 , e ntr y 2– 6) , c om-
wa s s ti rre d fo r 2 4 h t o g et wh it e p rec i pi ta t io n. The pou nd 3b-c ( Fi gur e 2 ) we r e is ola te d di re c tl y f rom the
m i x tu re wa s th e n di l ut e d wi th 2 mL D O, fil te r e d to r ea c ti on m ixt ur e by si mpl e fi ltr a ti on in th e sa lt- f r e e
c o l l e c t wh i te s o li d ma ss ( 61 mg , 71 %) . I t was dr ie d to f or m. Thi s is pr e sum a bly be c au se of e le ct r on- w ith-
2
1
g e t s p e c tro s c o p i c da t a. H- NM R i n DM SO -d6 is dr a wing gr ou p pr e se nt in th e a mi de pa r t ( en tr y 2–6,
e s se n tia ll y s a me wi th 3aHCl ex ce pt t he p osi tio n of Ta ble 1 ) , m ak ing th e te r ti ar y a mi ne c en te r le ss ba s ic .
1
re s id u al H O p re se nt i n t he DM SO-d so l ve nt. H- C omp ound 3b-d a re not r ep or te d in th e li te r at ur e . W e
2
6
NM R (4 0 0 M Hz , DM SO-d ) d 8 .43 ( d, J = 8Hz , 1H) , ha ve c onfi r me d th e st ru ct ur es by NMR a nd H RM S .
6
8
. 2 6 (d , J = 8 H z, 1H ), 8 .07 ( t, J = 8Hz , 1H) , C omp ound 3e, syn the si ze d und er th e a ci d- c a ta lyz e d
7
ES I -T OF- MS c a l cul a te d ma ss f or C H DN O is a nd o- pht ha la lde hyde wit h im pr ov ed is ola te d yie ld
. 9 4 –7 .8 8 (m , 3 H) , 7 .78 –7 .69 ( m, 2H ), 5 .71 ( s, 2H) ; c ondi tio n in 91% is ola te d yi el d f r om th e c om po und 4
?
15
10
2
9
a nd r ea c ti on c ondi tio n. C omp ound 3f wa s is ola te d a s
3
3 6 . 09 29 , o b s e rv ed m/z = 23 6 .09 95 .
Co m p o u n d 3aDCl was t re at ed wi th sat ur a te d a whi te sol id f r om th e e qui mol a r m ixt ur e of
b i c ar b o n at e a n d th e wh it e so l id o bt ai ne d af t e r ba se 2- a mi nobe nz e ne sul fo na mi de a nd o- pht ha la lde hyde
1
t re at m en t wa s s u bj e ct ed t o H- NM R. I t was e xa ct ly und er th e r ea c ti on c ondi tio n m en tio ne d in Ta ble 1 .
s a me a s o b s e rv e d f or 3a.
S ynt he sis of c om poun d 3f is r ep or te d in a mul tis te p
8
pr oc e dur e wit hout suf fi c ie nt spe c tr os cop ic da ta .
B ec a use of po or sol ubi lit y in c om mon or ga nic s ol-
3
. Results and Discussion
1 3
ve nt s, we we r e una bl e to c oll ec t C -NM R da ta of 3d.
I nve st iga ti on of sub str a te sc ope r ev ea l ed th a t the
e le ct r oni c na tu re of th e sub sti tue nt pr e se nt on the
a mi de m oie ty doe s not a ff e c t si gnifi c a ntl y on yie ld.
Ma i nly two ty pe s of m ec ha ni sti c pa th way s; na me ly,
At t h e o n s e t o f th e wo rk , we h ave st a rt ed sy nt he sis of
t h e c o mp o u n d 3a by us i ng t he co nd i ti on me nt i o ne d by
2
R e i n h a rd et. al. Eq ui mo l ar mi xt u re o f 2- ami nobe n-
z am i de o-p h t ha l a ld eh yd e sm oo th ly co nv er t e d in to
c o m p o u n d 3a in me th an ol an d 2 ( N) HCl ( aqu eou s) in
3 : 1 ra ti o a t ro o m t emp er at u re , f ro m wh ic h wh ite sol id
m a ss o f h y d ro c h lo r i de sa l t ( 3aHCl) se pa ra te d out . The
9
in tr am ol ec ul ar hy dr ide tr a nsf e r ( Pa t h- A) a nd ta u-
1 0
to me r ism ( Pa t h- B) ha ve be e n pr op ose d f or the r e a c-
ti on of o- pha la ld eh yde a nd st ru ct ur al ly si mi la r 1,5- N-
bi snuc le oph il es. P at h- A in volv es in tr am ol ec ula r 1,3-
9
hyd r ide tr a nsf e r ( as pr op ose d by Abd el -L at if et al. )
s o l i d ma s s wa s c o l le ct ed b y fil t ra t io n an d was h ed wit h
3
: 1 me t h a n o l wa te r pr o vi de d an al y ti ca l ly pu re c om -
wit hout th e pa r tic i pa tio n of sol ve nt pr ot on in the ke y
st ep . W he r ea s, in th e P at h- B ( Sc he m e 2 ) m ult iple ta u-
to me r ic se que nc e s by whi ch hyd r oge n a tom tr a ns f er r in g
wit h th e pa r tic i pa tio n of sol ve nt pr ot on m ay le a d to the
p o u n d 3aHCl. C rys tal li zati on of 3aHCl was c ar r ie d
o u t in a q . me t h a n ol an d t he st r uc tu re wer e sol ve d by
s i n gl e -c ry s t a l X-ra y di f fr ac t io n st u dy wh ic h is a va il-
a b l e a s S u p p le me nt ar y I nf or ma ti on . Cr ys ta l d at a a nd
s t ru c tu re (F ig u re 1) sh ows t ha t t he t et ra cy cl i c s ke le ton
i s in p la n e r g e o m et ry . Th e hy d ro gen bo n di ng of th e
a m i d e h y d ro g e n t hr ou gh a wat e r mo le cu l e f or ms a
n e t w o rk in th e s o l id . I t i s i nt er es t in g t o n ot e th at th e
p o s it io n o f th e h e t er oa to m i n t he st r uc tu re o f 3aHCl
1 0
c om poun d 3aHCl ( as pr op ose d by Ukh in et al. ) . To
c onfi r m th e m ec ha ni sti c pa th way f or th e f or ma tion of
3aHCl, we ha ve c ar r ie d out th e r ea c ti on of o- phtha -
la ld eh yde wit h 2- a mi nobe nz a mi de in DC l/C D O D a t
3
R T. W e ob ser ve d th e e xc lus ive f or ma t ion of c ompo und
3aDCl, but not 3aD Cl. F or f ur the r c onfi r mat ion of
2
(c ry s ta l s tr u c tu re ) i n so l id -s t at e i s d if fe re nt f ro m th at in
s o l ut io n -s t at e a s th er e i s ab se nt of am id e pr o to n in th e
1
H- NM R in DM S O-d so l ve nt . Co mpo un d 3aHCl wa s
6
c o n v e rte d to 3a by was hi n g wi th aq ue ou s Na HCO
3
1
s o l ut io n a n d H-N M R was ac co rd i ng t o t he s tr uc tur e
6, 7
a n d e x a c tly ma t c he d wi th t he r epo r te d d at a
Use of
o t h er mi ld L ew is ac i d r esu l te d i n l ow y ie ld . Apr ot ic
s o l ve n t DM F c a n b e us ed ; h owev er me th ano l or
e t ha n o l me d i u m be ne fit s pr o du ct i so la t io n wit hout
c o l um n p u ri fic a ti on . W e us ed me th an ol f or syn the -
s i z i n g th e c o mp o un ds me nt i on ed he re .
Us in g th e a b ov e- me nt i on ed co nd i ti on , sub str a te
s c o p e wa s in v e s t ig at ed wi th di f fe re nt su b sti tut ed
a m i d e . W e h a v e sy nt h es iz ed v ari e ti es of t he sub sti -
t u t e d te t ra c y c lic sk el et o n ( 3b-d) . No ta bl y, f or th e
Figure 1. C rys t al s t ruct ur e of 3aHCl

6
3
Pa g e 4 o f 5
J. Chem. Sci. (2 020) 1 32: 63
Table 1. Sy n t h es is of is o in do l e f us e d qu in a zo li n 4- one s
a ssum e d to be e sse nti a lly sa m e a s pr op ose d by A bde l-
9
La ti f et al. ( Pa t h- A, S ch em e 2 . The m et hod invo lve s
in iti al f or ma t ion of m onom e r ic c om poun d 5, f o llow ed
by im in ium io n (6) f or ma t ion. The subs e que nt
in tr am ol ec ul ar 1,3 -h ydr ide tr a nsf e r ga ve c ompo und
3aDCl. Af te r th e tr e a tm en t of 3aDCl wit h a que ous
En t r y
A m id e
Pr oduc t
Na HCO th e r es ult an t out c om e wa s 3a.
3
1
2
3
4
2 -A mi no be n za mi de
2 -a m in o- 5 -n it r ob enz am id e
2 -a m in o- 5 -b ro m ob en za m id e
2 -a m in o- 3 ,5-
3aHCl
3b
3c
4. Conclusions
3d
d i b r o m ob en za m id e
C o mp o u n d 4
2 -a m in ob en zen es u lf on a m id e
I n sum m ar y, on e- pot syn the si s of is oind ole f us ed
qu ina z olin -4 on es wa s c ar r ie d out in th e pr e se nce of a n
a ci d c at al yst . El ec tr on ic na tu re of sub sti tue nts on
a mi de si de ha ve a ne gl igi ble e ff e c t on th e ke y s te p
in tr am ol ec ul ar hy dr ide tr a nsf e r . The m ec ha ni sti c s tudy
un der de ut er a te d sol ve nt r ev ea l ed th at th e re a c tion
pr oc e ed s th ro ugh in tr am ol ec ul ar 1,3 -h ydr ide tr a ns f er
r ea c ti on. F ur the r st udy ne e de d to un der st a nd th e s te r eo
c he mi ca l a spe c t of th e hyd r ide tr a nsf e r r ea c ti on . The
m et hod c oul d be a ppl ic ab le wit h di ff e r en tly s ubst i-
tu te d o- pht ha la de hyde de r iva ti ve s.
5
6
3e
3f
Re act i o n c o nd i t i o n s : al deh yd e ( 2.5 0 m m ol ) , am i de (2 .50
m m o l ), i n 3 0 m L Me OH an d 10 m L H Cl ( 2 N) at RT fo r 24
h
s t ru c tu re 3aDCl, i t was t re at ed wi th aq ue ou s Na HCO3
a n d o b s e rv e d th e fo r mat i on of 3a. Th e NM R an d HR MS
s p e c tra o f 3a o b t ai ne d f ro m t he ab ov e men tio ne d
d e u te ra te d e x p e rime nt sh ows no d eut e ri um i nc or por a -
t i o n in th e s tr u c tu re 3a. Fo rm at io n of 3aDCl a nd 3a
u n d e r d e u te ra te d so l ve nt cl e ar ly sh ows t ha t t h e r ea r -
Supplementary Information (SI)
ra n g e me n t o f in it i al i nt er me di at e 6 i nt o 3a is C rys t al l ogr aphi c d at a fo r t he s t ruct ur e s 3aH Cl i n t hi s p ap er
hav e bee n dep os i t ed wi t h t he C am bri d ge C rys t al log r a ph i c
i n t ra m o le cu l a r h yd r id e t ra ns fe r as sh own i n Pa th- A in
Dat a C ent re as s upp lem ent ar y pub li cat i on no s . CC D C
Sc h em e 2 . T h e 1 ,3 -h yd ri de t ra ns fe r i s b ei ng f ac ili ta te d
190 7967 . C op i es of t he dat a can b e obt a i ned, fr ee of c ha rg e ,
b y th e e le c tr o n -ri ch am id e n it r og en do n or ce nt er . Ac id-
c at a ly z e d in t ra m ol ec ul ar hy d ri de t ra ns fe r f ro m sp3
c ar b o n a d ja c e n t of ni t r og en ce nt er t o cl o sel y spa c e d
e l ec tr o p h il i c c e n te r i s wel l -k no wn an d an es t abl ishe d
on app li ca t io n t o C CD C , 12 Un ion R oa d, C a m br idg e CB 2
EZ, UK , (f a x: ?44- (0) 122 3- 3360 33 or e -m a il :
1
dep os it @cc dc. c am . ac. U k) S upp lem e nt ary i nf or m ati o n c on -
t ai nin g cry s t al s t ruct ur e and refi n e m ent par am e t er s a nd
s pec tr a are ava i l abl e at ht t ps : // w ww .i as . ac. in /ch e m s c i .
1
1
p h e n o m en o n .
B a s e d o n th e de ut e ra te d so l ve nt ex pe ri me nt , th e
p ro p o s e d me c h a n i sm f or t he f or mat i on o f 3a is
Figure 2. S tr uc tu r e of th e s ynt hes i zed i s oi ndol e fu s ed qui na zol i n 4- one s

J. Chem. Sci. (2 0 2 0 ) 13 2: 63
P age 5 of 5 63
Scheme 2. P o s s i bl e m ech ani s m
Acknowledgements
2, 3-d ih ydr oqu in azo li n- 4(1 H) -one s J. Mol. Catal. A 395
72
. Mha s k e S B and Ar gad e N P 200 6 The che mi s tr y o f
rec ent ly i s ol ate d nat u ral l y o ccu rri ng qui na zo l i no n e
al kal oi ds Tetrahedron 62 978 7
1
Au t h o r s a re t h an k fu l to th e S ERB N ew D elh i , ( EMR /2 014 /
0
5
0 0 5 4 2 ) a n d J ad a v pu r U niv er s it y, K olk at a f or fi nan ci al
s u pp o r t . Sp e ci a l t h an ks to D r. P . Ma ha ta , D epa rtm ent of
Ch em i s t ry , J U fo r hi s ki nd s up po rt f or s ol v in g cry s ta l
s tr u c tu re .
6. S un X, Hu Y, Ni e S -z, Yan Y- y, Zh ang X- j and Ya n M
01 3 Effi ci ent con s tr uc t io n of C =N dou bl e bo nd s v ia
2
acce pt or l es s deh ydr oge nat i ve cou pl i ng Adv. Synth.
Catal. 355 217 9
7
. B akavo l i M, Dav ood ni A, R ahi m i zad eh M and He r a vi
M M 200 6 S ynt he s i s of di be nzo [b, g][ 1, 5]d iaz o ni n e-
di one and i s oi ndol o[ 2, 1-a ]q ui nazo l in e der iv ati v e s Men-
deleev Commun. 16 29
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