untitled


European	Journal	of	Chemistry	2	(2)	(2011)	200‐205	

	
European	Journal	of	Chemistry	

ISSN	2153‐2249	(Print)	/	ISSN	2153‐2257	(Online)		2011	EURJCHEM	
DOI:10.5155/eurjchem.2.2.200‐205.365	

	
	

	

	

European	Journal	of	Chemistry	
Journal	homepage:	www.eurjchem.com	

	 	 	

Utility	of	2‐cyano‐3‐phenyl‐2‐propenoyl	chloride	as	Michael’s	acceptor	
in	heterocyclic	synthesis	with	mono‐	and	bi‐dentate	nucleophiles	

Sayed	Ahmed	Shibaa,	Hassan	Mohamed	Fawzy	Madkoura,b,*,	Ashraf	Ahmed	Hameda,		
Hatem	Mohamed	Sayeda	and	Maher	Abd	El‐aziz	El‐Hashasha	

a	Chemistry	Department,	Faculty	of	Science,	Ain	Shams	University,	Abbasiya,	11566,	Cairo,	Egypt	
b	Institute	of	Biochemistry,	University	of	Balochistan,	Quetta,	87300,	Pakistan	

*Corresponding	author	at:	Chemistry	Department,	Faculty	of	Science,	Ain	Shams	University,	Abbasiya,	11566,	Cairo,	Egypt.	Tel.:	+202.24831836;		
fax:	+202.24831836.	E‐mail	address:	fawzy.hassan@ymail.com	(H.M.F.	Madkour).	

	
	

	 	

	 	 	
ARTICLE	INFORMATION	 	 ABSTRACT
Received:	07	December	2010	
Received	in	revised	form:	05	April	2011	
Accepted:	05	April	2011	
Online:	30	June	2011	

KEYWORDS	

	 (E)	2‐Cyano‐3‐phenyl‐2‐propenoyl	chloride	reacts	with	nitrogen,	oxygen	and	sulphur	mono‐
and	bi‐dentate	 nucleophilic	 reagents	 to	 give	 the	 amide	derivatives,	 the	 ester	 derivatives,	 as
well	 as	 some	 heterocyclic	 systems,	 namely	 quinazolinone,	 pyridopyrimidine	 and
benzothiazepine.	 Cyclization	 of	 some	 obtained	 amides	 affords	 the	 benzoxazinones,
quinazolinone,	whereas	that	of	other	amides	yields	oxadiazole	and	benzoxazole,	respectively.	

Mono‐	and	bi‐dentate	nucleophiles	
2‐propenoyl	chloride	
Benzoxazinone	
Quinazolinone	
Oxadiazole	
Benzoxazole	

	
1.	Introduction	
	

The	 recent	 pharmaceutical	 applications	 of	 2‐propenoyl	
amides	 [1],	 2‐propenoates	 [2,3],	 and	 other	 heterocyclic	
skeletons,	 like	 benzoxazinones	 [4,5],	 quinazolinones	 [6],	
benzoxazoles	 [7‐9],	 oxadiazoles	 [10]	 have	 stimulated	 the	
authors	 to	 synthesize	 new	 derivatives	 of	 these	 classes	 of	
compounds	hoping	to	obtain	structures	with	possibly	enhanced	
potency.	

In	continuation	of	our	ongoing	program	in	the	synthesis	of	
biologically	 active	 heterocyclic	 systems	 from	 simple	 readily	
obtainable	materials	[11‐21],	the	present	work	investigates	the	
reactivity	 of	 high	 functionality	 2‐cyano‐3‐phenyl‐2‐propenoyl	
chloride	 [22]	 (1)	 with	 different	 mono‐	 and	 bi‐dentate	
nucleophiles	aiming	to	obtain	new	derivatives	with	anticipated	
biological	activities.	
	
2.	Experimental	

	
Melting	 points	 reported	 have	 been	 measured	 on	 a	 Stuart	

Scientific	melting	point	apparatus	and	are	uncorrected.	The	IR	
spectra	 were	 recorded	 on	 Pye	 Unicam	 SP	 1200	
spectrophotometer	using	KBr	wafer	technique.	1H	NMR	spectra	
were	 determined	 on	 a	 Varian	 FT‐200,	 and	 a	 Bruker	 AC‐200	
MHz	spectrometer	using	TMS	as	internal	standard.	All	chemical	
shifts	 (δ)	 are	 expressed	 in	 ppm.	 All	 the	 NH	 or	 OH	 protons	
disappeared	 on	 addition	 of	 D2O.	 The	 mass	 spectra	 were	
determined	 using	 MP	 model	 MS‐5988	 and	 Shimadzu	 single	
focusing	 mass	 spectrophotometer	 (70	 eV).	 Compound	 1	 has	
been	 synthesized	 according	 to	 Jaafar	 et	 al.	 method	 [22].	 The	
conduction	time	of	all	reactions	and	the	purity	of	the	products	

were	 monitored	 using	 thin‐layer	 chromatography	 (TLC)	
technique.	

	
2.1.	N‐[2‐Cyano‐3‐phenyl‐2‐propenoyl]benzylamine	(2)	

	
To	a	solution	of	propenoyl	chloride	(1)	(1.9	g;	10	mmol)	in	

dry	benzene	(30	mL)	in	presence	of	triethylamine	(1.38	mL;	10	
mmol),	 benzylamine	 (1.08	mL;	 10	mmol)	 was	 added	 and	 the	
reaction	mixture	was	stirred	at	room	temperature	for	an	hour.	
The	 solid	 formed	 was	 collected,	 washed	 with	 water	 several	
times,	 dried	 and	 crystallized	 from	 benzene	 to	 yield	 2	 as	
colourless	 crystals	 (Scheme	 1).	 Yield:	 60%.	 M.p.:	 135‐137	 oC.	
FT‐IR	 (KBr,	 cm‐1):	 3337	 (NH),	 2220	 (CN),	 1663	 (C=O)	
(amide).	 1H	NMR	(300	MHz,	DMSO‐d6):	4.44	 (d,	2H,	 J	=	20	Hz,	
CH2‐NH),	 7.24‐7.95	 (m,	 10H,	 Ar‐H),	 8.21	 (s,	 1H,	 =CH),	 8.97	 (t,	
1H,	J	=	20	Hz,	NH‐CH2).	MS	(EI,	m/z):	262	(M.+).	Anal.	Calcd.	for	
C17H14N2O:	C,	77.86;	H,	5.34;	N,	10.68.	Found:	C,	77.54;	H,	5.66;	
N,	10.29%.	

	
2.2.	N‐(4‐methoxyphenyl)2‐cyano‐3‐phenyl‐2‐propenoyl	
amide	(3)	

	
To	a	solution	of	1	(1.9	g;	10	mmol)	in	dry	benzene	(30	mL)	

in	 presence	 of	 triethylamine	 (1.38	mL;	 10	mmol),	p‐anisidine	
(1.22	g;	10	mmol)	was	added.	The	reaction	mixture	was	stirred	
at	room	temperature	for	an	hour.	The	semisolid	produced	was	
collected,	washed	with	water	several	times,	and	then	triturated	
with	methyl	 alcohol.	 The	 solid	 separated	was	 collected,	 dried	
and	 crystallized	 from	 methanol	 to	 give	 3	 as	 yellow	 crystals	
(Scheme	 1).	 Yield:	 60%.	 M.p.:	 155‐157	 oC.	 FT‐IR	 (KBr,	 cm‐1):	
3312	(NH),	2220	(CN),	1676	(C=O)	(amide).		



Shiba	et	al.	/	European	Journal	of	Chemistry	2	(2)	(2011)	200‐205	 201	
 

 
 

	

Ar C

O

Cl

Ar C

O

X Ar`

R-NH2

NH2

NH2

NH2OH

NH-CO-Ar

NH-CO-Ar

Ar C

O
H
N R

Ar C

O

O CH2 CH2 HN C

O

Ar

CN

H

Ar`-XH

N
H

N

Ar

AlCl3

N
H

CN

O

(1)

(8)

(7)

2) R = C6H5-CH2-
3) = C6H4-OCH3 (4)

5) X = O, Ar` = C6H4-CH3(2)
6) = S, = C6H4-CH3(4)

Ar =

POCl3 or D

(B)

(A)

H3CO

NH2

COOH

Et3N/Bz

or Pyr./r.t

Pyri/ref.

Ar C

O
H
N

HOOC

(9)

Ac2O

N

O

O

Ar

N

NH

O

Ar

AcONH4

(10)

(11)

140-160°C

N2H4/EtOH

CONH-N=CH-Ph

NH-CO-CH2-CN

(15)

N

N

O

Ar

HOOC

Ac2O

N

O

O

HN C

O

Ar

(12)

+

(14)

+ (10) + (12)
(b)

(a)
-H2O

-H2O

H
NCAr

O

CO

HN

HOOC

(13)

COOH

NH2

COOH

NH2

(a) -
EtOH
12:13 = 10:90%

/ 12:13 = 80:20%

NH2

COOH

N NH2
N

N

O

CNPh

PhCONHNH2

OH
NH2

H
NC

O

Ar

HO

C

O

Ar C

O
H
N

H
N Ph

POCl3

POCl3

O

N

Ar

N

O

N

PhAr

(16)

(18)

(20)

(21)

(19)

(-H2O)

(-H2O)

NH2

SH
S

HN O

CNPh

(17)

4) R = C6H4-OH (4)

Ar C

O
H
N R

Ph

 
	

Scheme	1



202	 Shiba	et	al.	/	European	Journal	of	Chemistry	2	(2)	(2011)	200‐205	
	

	

1H	NMR	(300	MHz,	DMSO‐d6):	3.75	(s,	3H,	OCH3),	6.91‐7.94	(m,	
9	H,	Ar‐H),	8.25	 (s,	1H,	=CH),	10.25	 (s,	1H,	NH).	MS	 (EI,	m/z):	
278(M.+).	Anal.	Calcd.	for	C17H14N2O2:	C,	73.38;	H,	5.03;	N,	10.07.	
Found:	C,	73.11;	H,	5.41;	N,	10.32%.	

	
2.3.	N‐(4‐hydroxyphenyl)	2‐cyano‐3‐phenyl‐2‐propenoyl	
amide	(4)	

	
A	mixture	of	3	 (1.4	 g,	5	mmol)	and	anhydrous	aluminium	

chloride	 (1.33	 g,	 10	 mmol)	 in	 dry	 benzene	 or	 chlorobenzene	
(50	mL)	was	stirred	at	room	temperature	for	three	hours,	then	
refluxed	for	24	hours	and	 left	overnight.	The	reaction	mixture	
was	 poured	 onto	 cold	 dilute	 HCl.	 The	 organic	 solvent	 was	
removed	by	steam	distillation	and	the	residue	was	extracted	by	
diethyl	 ether	 (3	 x	 50	 mL),	 and	 then	 dried	 over	 anhydrous	
MgSO4.	The	diethyl	 ether	was	 removed	by	distillation	and	 the	
residue	 was	 crystallized	 from	 methanol	 to	 give	 4	 as	 green	
crystals	 (Scheme	 1).	 Yield:	 90‐95%.	 M.p.:	 195‐196	 oC.	 FT‐IR	
(KBr,	 cm‐1):	 3338,	 3258	 (NH),	 2222	 (CN),	 1653	 (C=O)	
(amide).	 1H	NMR	(300	MHz,	DMSO‐d6):	6.75‐7.96	 (m,	9	H,	Ar‐
H),	8.22	(s,	1H,	=CH),	9.36	(s,	1H,	NH),	10.14	(s,	1H,	OH).	MS	(EI,	
m/z):	264	(M+).	Anal.	Calcd.	for	C16H12N2O2:	C,	72.72;	H,	4.54;	N,	
10.61.	Found:	C,	73.00;	H,	4.42;	N,	10.31%.	

	
2.4.	General	procedure	to	synthesize	compounds	5,	6,	7,	8,	9,	
17,	18	and	20	

	
To	a	solution	of	propenoyl	chloride	(1)	(1.9	g;	10	mmol)	in	

dry	 benzene	 (30	 mL)	 containing	 triethylamine	 (1.38	 mL;	 10	
mmol),	 o‐cresol,	 p‐thiocresol,	 ethanolamine,	 o‐phenylene	
diamine,	 anthranilic	 acid,	 2‐aminothiophenol,	 benzoyl	
hydrazine	 and/or	 2‐aminophenol	 (10	 mmol)	 was	 added	 and	
the	reaction	mixture	was	stirred	at	room	temperature	for	1	h.	
The	 triethylamine	 hydrochloride	was	 filtered	 off	 and	most	 of	
the	 solvent	was	distilled	off.	The	 solid	 that	 separated	out	was	
collected	 by	 suction	 and	 recrystallized	 from	 the	 appropriate	
solvent	to	afford	the	desired	product	(Scheme	1).	

2‐Methyphenyl	 2‐cyano‐3‐phenyl‐2‐propenoate	 (5):	 Comp‐
ound	5	crystallized	from	benzene	to	give	green	crystals.	Yield:	
85%.	 M.p.:	 101‐103	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 2220	 (CN),	 1734	
(C=O)	(ester).	1H	NMR	(300	MHz,	DMSO‐d6):	2.20	(s,	3H,	CH3),	
7.27‐8.15	 (m,	9	H,	Ar‐H),	8.64	 (s,	1H,	=CH).	MS	 (EI,	m/z):	263	
(M+.).	 Anal.	 Calcd.	 for	 C17H13NO2:	 C,	 77.56;	 H,	 4.94;	 N,	 5.32.	
Found:	C,	77.24;	H,	4.82;	N,	5.54%.	

S‐4‐Methyphenyl	 2‐cyano‐3‐phenyl‐2‐propenthioate	 (6):	
Compound	6	crystallized	from	benzene	to	give	yellow	crystals.	
Yield:	 90%.	 M.p.:	 110‐112	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 2216	 (CN),	
1662	(C=O)	(thioester).	1H	NMR	(300	MHz,	DMSO‐d6):	2.37	(s,	
3H,	CH3),	 7.32‐	8.09	 (m,	9	H,	Ar‐H),	 8.40	 (s,	 1H,	=CH).	MS	 (EI,	
m/z):	279	(M.+).	Anal.	Calcd.	for	C17H13NOS:	C,	73.11;	H,	4.65;	N,	
5.01.	Found:	C,	73.26;	H,	4.52;	N,	5.28%.	

2‐N‐(2`‐Cyano‐3`‐phenyl‐2`‐propenoyl)‐1‐O‐(2`‐cyano‐3`‐
phenyl‐2`‐propenoyl)ethanolamine	 (7):	 Compound	 7	 crystal‐
lized	 from	n‐butanol	 to	 give	 yellow	 crystals.	 Yield:	 60%.	M.p.:	
212‐214	 oC.	FT‐IR	 (KBr,	 cm‐1):	3442	(NH),	2208	(CN),	1726	
(C=O)	 (ester),	 1684	 (C=O)	 (amide).	 1H	 NMR	 (300	 MHz,	
DMSO‐d6):	3.59	(q,	2H,	CH2‐NH),	4.40	(t,	2H,	CH2‐O),	7.54‐8.05	
(m,	10H,	Ar‐H),	8.44	(s,	1H,	=CH),	8.70	(s,	1H,	=CH),	8.87	(t,	1H,	J	
=	20Hz,	NH‐CH2).	MS	(EI,	m/z	(%)):	371	(M+.).	Anal.	Calcd.	 for	
C22H17N3O3:	C,	71.15;	H,	4.58;	N,	11.32.	Found:	C,	70.77;	H,	4.33;	
N,	11.67%.	

(2E,2'E)‐N,N'‐(1,2‐phenylene)bis(2‐cyano‐3‐phenylacryl	
amide)	 (8):	 Compound	 8	 crystallized	 from	 n‐butanol	 to	 give	
yellow	crystals.	Yield:	62%.	M.p.:	215‐218	oC.	FT‐IR	(KBr,	cm‐1):	
3298	(NH),	2216	(CN),	1672	(C=O)	 (amide).	 1H	NMR	(300	
MHz,	DMSO‐d6):	7.32‐7.98	(m,	14	H,	Ar‐H),	8.36	(s,	2H,	2	x	=CH),	
9.92	(s,	br,	2H,	2xNH).	MS	(EI,	m/z):	418	(M.+).	Anal.	Calcd.	for	
C26H18N4O2:	C,	73.23;	H,	4.22;	N,	15.02.	Found:	C,	72.81;	H,	4.17;	
N,	15.07%.	

2‐N‐(2‐Cyano‐3‐phenyl‐2‐propenoyl)aminobenzoic	 acid	 (9):	
Compound	9	crystallized	from	benzene/EtOH	to	give	colourless	
crystals.	Yield:	85%.	M.p.:	248‐250	oC.	FT‐IR	(KBr,	cm‐1):	2848,	
3167	 (NH)	 and	 	 (OH),	 2208	 (CN),	 1674	 (C=O).	 1H	 NMR	
(300	MHz,	DMSO‐d6):	7.27‐8.62	(m,	10	H,	=CH,	Ar‐H),	11.33	(s,	
1H,	CO‐NH),	12.23	(s,	1H,	COOH).	MS	(EI,	m/z):	292	(M.+).	Anal.	
Calcd.	for	C17H12N2O3:	C,	69.86;	H,	4.11;	N,	9.58.	Found:	C,	70.17;	
H,	4.01;	N,	9.79%.	

2‐oxo‐4‐phenyl‐2,3,4,5‐tetrahydrobenzo[b][1,4]thiazepine‐3‐
carbonitrile	 (17):	 Compound	 17	 crystallized	 from	 dioxane	 to	
give	yellow	crystals.	Yield:	50%.	M.p.:	222‐224	 oC.	FT‐IR	(KBr,	
cm‐1):	3190	(NH),	2247	(CN),	1672	(C=O)	(thiazapinone).	1H	
NMR	(300	MHz,	DMSO‐d6):	4.58	(d,	1H,	J	=	22	Hz,	‐CH‐CN),	5.16	
(d,	1H,	J	=	7	Hz,	Ph‐CH‐CH‐CN),	7.22‐7.69	(m,	9H,	Ar‐H),	10.52	
(s,	1H,	NH).	MS	(EI,	m/z):	280	(M.+).	Anal.	Calcd.	for	C16H12N2OS:	
C,	69.06;	H,	3.59;	N,	10.07.	Found:	C,	69.38;	H,	3.40;	N,	10.39%.	

N`‐(2‐cyano‐3‐phenyl‐2‐propenoyl)benzohydrazide	 (18):	
Compound	 18	 crystallized	 from	 benzene/ethanol	 to	 give	
colourless	 crystals.	 Yield:	 65%.	 M.p.:	 201‐203	 oC.	 FT‐IR	 (KBr,	
cm‐1):	3210	(NH),	2208	(CN),	1679	(C=O)	(amide).	1H	NMR	
(300	 MHz,	 DMSO‐d6):	 7.52‐7.98	 (m,	 10H,	 Ar‐H),	 8.27	 (s,	 1H,	
=CH),	10.57	(s,	2H,	2	x	NH).	MS	(EI,	m/z):	291	(M.+).	Anal.	Calcd.	
for	C17H13N3O2:	C,	70.10;	H,	4.46;	N,	14.43.	Found:	C,	69.81;	H,	
4.55;	N,	14.74%.	

2‐N‐(2`‐Cyano‐3`‐phenyl‐2`‐propenoyl)aminophenol	 (20):	
Compound	 20	 crystallized	 from	 benzene	 to	 give	 yellow	
crystals.	Yield:	50%.	M.p.:	208‐210	oC.	FT‐IR	(KBr,	cm‐1):	3368,	
3201	(OH)	and	(NH),	2211	(CN),	1663	(C=O)	 (amide).	 1H	
NMR	(300	MHz,	DMSO‐d6):	6.81‐8.01(m,	9H,	Ar‐H),	8.35	(s,	1H,	
=CH),	9.29	(br	s,	1H,	NH),	10.02	(s,	1H,	OH).	MS	(EI,	m/z):	264	
(M.+).	 Anal.	 Calcd.	 for	 C16H12N2O2:	 C,	 72.72;	 H,	 4.54;	 N,	 10.61.	
Found:	C,	72.69;	H,	4.84;	N,	10.95%.	

	
2.5.	2‐[1‐Cyano‐2‐phenyl‐ethen‐1‐yl]‐(4H)‐3,1‐benzoxazin‐4‐
one	(10)	
	

A	 mixture	 of	 benzoic	 acid	 derivative	 9	 (3	 g)	 and	 freshly	
distilled	acetic	anhydride	(10	mL)	was	heated	on	water	bath	for	
an	 hour.	 The	 solid	 separated	 out	 at	 room	 temperature	 was	
collected,	washed	with	dry	petroleum	ether	40‐60C,	dried	and	
crystallized	 from	 light	 petroleum	 (80‐100	 oC)	 to	 give	 10	 as	
yellow	crystals	(Scheme	1).	Yield:	88%.	M.p.:	190‐192	oC.	FT‐IR	
(KBr,	 cm‐1):	 2227	 (CN),	 1765	 (C=O)	 (oxazinone).	 1H	 NMR	
(300	 MHz,	 DMSO‐d6):	 7.60‐8.19	 (m,	 9	 H,	 Ar‐H),	 8.46	 (s,	 1H,	
=CH).	 MS	 (EI,	 m/z):	 274	 (M.+).	 Anal.	 Calcd.	 for	 C17H10N2O2:	 C,	
74.45;	H,	3.64;	N,	10.21.	Found:	C,	74.66;	H,	3.25;	N,	9.87%.	
	
2.6.	2‐(1‐Cyano‐2‐phenyl‐ethen‐1‐yl)‐quinazolin‐4(3H)‐one	
(11)	

	
A	 mixture	 of	 benzoxazinone	 10	 (0.9	 g;	 3	 mmol)	 and	

ammonium	acetate	(1	g;	12	mmol)	was	heated	without	solvent	
at	 160‐170	 oC	 for	 four	 hours.	 The	 solid	 mass	 was	 triturated	
with	 warm	 water.	 The	 solid	 separated	 was	 filtered,	 washed	
with	water	 several	 times,	 dried	and	 crystallized	 from	dioxane	
to	yield	11	as	yellow	crystals	(Scheme	1).	Yield:	60%.	M.p.:	301‐
303	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 3183	 (NH),	 2228	 (CN),	 1676	
(C=O)	 (quinazolinone).	 1H	 NMR	 (300	 MHz,	 DMSO‐d6):	 7.55‐
8.16	(m,	10	H,	=CH,	Ar‐H),	8.50	(s,	1H,	NH).	MS	(EI,	m/z):	273	
(M.+).	 Anal.	 Calcd.	 for	 C17H11N3O:	 C,	 74.72;	 H,	 4.02;	 N,	 15.38.	
Found:	C,	75.11;	H,	3.84;	N,	15.68%.	
	
2.7.	2‐(1‐Cyano‐2‐phenyl‐ethen‐1‐yl)‐3‐(2‐carboxyphenyl)	
quinazolin‐4‐one	(12)	and	(E)‐2‐(2‐(2‐cyano‐3‐phenyl	
acrylamido)benzamido)benzoic	acid	(13)	

	
A	mixture	of	1	(1.9	g;	10	mmol)	and	anthranilic	acid	(1.36	g,	

10	mmol)	in	dry	pyridine	(30	mL)	was	refluxed	for	two	hours.	
After	cooling	the	mixture	was	acidified	with	cold	dilute	HCl.	The	



Shiba	et	al.	/	European	Journal	of	Chemistry	2	(2)	(2011)	200‐205	 203	
 

 
 

precipitate	formed	was	collected,	washed	with	water,	dried	and	
triturated	 by	 ethanol	 then	 fractionally	 crystallized	 to	 afford	
quinazolinone	12	and	benzamide	derivative	13	(Scheme	1).	

Compound	 12	 crystallized	 from	 light	 petroleum	 (80‐100	
oC)	to	give	yellow	crystals.	Yield:	65%.	M.p.:	190‐192	oC.	FT‐IR	
(KBr,	 cm‐1):	 3750,	 3315	 (OH)	 and	 (NH),	 2213	 (CN),	 1693	
(C=O)	(acid),	1660	(C=O)	(cyclic	amide).	1H	NMR	(300	MHz,	
DMSO‐d6):	7.24‐8.59	(m,	14	H,	=CH,	Ar‐H),	12.09	(s,	1H,	OH).	MS	
(EI,	 m/z):	 393	 (M.+).	 Anal.	 Calcd.	 for	 C24H15N3O3:	 C,	 73.28;	 H,	
3.84;	N,	10.68.	Found:	C,	73.01;	H,	4.00;	N,	10.90%.	

Compound	 13	 crystallized	 from	 benzene/ethanol	 to	 give	
brown	crystals.	Yield:	15%.	M.p.:	220‐223	oC.	FT‐IR	(KBr,	cm‐1):	
3340,	 2640	 (OH)	 and	 (NH),	 2210	 (CN),	 1681	 (C=O).	 1H	
NMR	 (300	 MHz,	 DMSO‐d6):	 7.22	 ‐8.62	 (m,	 14H,	 =CH,	 Ar‐H),	
11.63	 (s,	 1H,	NH),	 12.07	 (s,	 1H,	NH),	 12.22	 (s,	 1H,	 COOH).	MS	
(EI,	 m/z):	 411	 (M.+).	 Anal.	 Calcd.	 for	 C24H17N3O4:	 C,	 70.07;	 H,	
4.17;	N,	10.21.	Found:	C,	70.31;	H,	3.92;	N,	10.00%.	

	
2.8.	Conversion	of	benzoxazinone	(10)	into	(12)	and	(13)	

	
Procedure	 (I)	 in	 ethanol:	 A	 mixture	 of	 benzoxazinone	 10	

(1.49	g;	5	mmol)	and	anthranilic	acid	(0.9	g;	5	mmol)	in	ethanol	
(50	mL)	was	refluxed	for	3	h.	The	solvent	was	distilled	off	and	
the	residue	was	fractionally	crystallized	to	give	12	in	10%	yield	
and	13	in	90%	yield	(Scheme	1).	

Procedure	 (II)	heating	without	 solvent:	The	 same	 previous	
mixture	was	heated	at	140‐160	oC	without	solvent	for	1	h.	After	
cooling,	the	residue	was	fractionally	crystallized	to	give	12	and	
13	in	80%	and	20%	yield,	respectively	(Scheme	1).	
	
2.9.	2‐[2‐N‐(2‐Cyano‐3‐phenyl‐2‐propenoyl)amino]phenyl‐
4H‐benzo[d][1,3]oxazin‐4‐one	(14),	(10)	and	(12)	

	
A	 mixture	 of	 benzamide	 derivative	 (13)	 (2	 g)	 and	 acetic	

anhydride	 (30	mL)	was	 heated	 on	water	 bath	 for	 two	 hours,	
and	 then	 poured	 into	 crushed	 ice.	 The	 solid	 separated	 was	
collected,	 washed	 with	 water,	 dried	 and	 fractionally	
crystallized	to	give	a	mixture	of	10,	 	 	12	and	14	 in	5,	25,	45%	
yields,	respectively	(Scheme	1).	

Compound	14	 was	 crystallized	 from	 dioxane	 to	 give	 pale	
yellow	crystals.	Yield:	45%.	M.p.:	271‐274	oC.	FT‐IR	(KBr,	cm‐1):	
3172	 (NH),	 2208	 (CN),	 1763	 (C=O)	 (oxazinone),	 1695	
(C=O)	(amide).	1H	NMR	(300	MHz,	DMSO‐d6):	7.03‐8.10	(m,	13	
H,	Ar‐H),	8.21	(s,	1H,	CN‐C=CH),	10.23	(s,	1H,	NH).	MS	(EI,	m/z):	
393	 (M.+).	 Anal.	 Calcd.	 for	 C24H15N3O3:	 C,	 73.28;	 H,	 3.84;	 N,	
10.68.	Found:	C,	73.42;	H,	3.61;	N,	10.55%.	

	
2.10.	N‐[2‐(2‐benzylidenehydrazinecarbonyl)phenyl]‐2‐
cyanoacetamide	(15)	

	
A	 mixture	 of	 benzoxazinone	 10	 (1.49	 g;	 5	 mmol)	 and	

hydrazine	 hydrate	 (0.1	mL,	 5	mmol)	 in	 ethanol	 (50	mL)	was	
refluxed	 for	 3	 h.	 The	 solid	 separated	 after	 concentration	was	
collected	 and	 crystallized	 from	 ethanol	 to	 yield	 15	 as	 pale	
yellow	crystals	(Scheme	1).	Yield:	55%.	M.p.:	140‐142	oC.	FT‐IR	
(KBr,	 cm‐1):	 3240,	 3192	 (NH),	 2212	 (CN),	 1696	 (C=O)	
(amide).	 1H	 NMR	 (300	 MHz,	 DMSO‐d6):	 3.91	 (s,	 2H,	 CH2‐CN),	
7.30‐8.49	(m,	10	H,	=CH,	Ar‐H),	11.49	(br	s,	1H,	2NH).	MS	(EI,	
m/z):	306	(M.+).	Anal.	Calcd.	for	C17H14N4O2:	C,	66.60;	H,	4.60;	N,	
18.28.	Found:	C,	66.33;	H,	4.72;	N,	18.01%.	

	
	

2.11.	2‐oxo‐4‐phenyl‐2H‐pyrido[1,2‐a]pyrimidine‐3‐
carbonitrile	(16)	

	
To	a	solution	of	1	(1.9	g;	10	mmol)	in	dry	benzene	(30	mL)	

in	 presence	 of	 triethylamine	 (1.38	 mL;	 10	 mmol),	 2‐
aminopyridine	 (0.9	 g;	 10	 mmol)	 was	 added.	 The	 reaction	

mixture	was	stirred	at	room	temperature	for	1	h.	The	semisolid	
produced	was	collected,	washed	with	water	several	times,	and	
then	 triturated	 with	methyl	 alcohol.	 The	 solid	 separated	 was	
collected,	dried	and	crystallized	from	methanol	to	afford	16	as	
colourless	 crystals.	 Yield:	 40%.	 M.p.:	 203‐205	 oC.	 FT‐IR	 (KBr,	
cm‐1):	 2218	(CN),	 1705	(C=O)	 (cyclic	 amide).	 1H	NMR	 (300	
MHz,	 DMSO‐d6):	 7.59‐9.80	 (m,	 9	 H,	 Ar‐H).	 MS	 (EI,	 m/z):	 247	
(M.+).	 Anal.	 Calcd.	 for	 C15H9N3O:	 C,	 72.87;	 H,	 3.64;	 N,	 17.01.	
Found:	C,	72.43;	H,	3.71;	N,	17.23%.	

	
2.12.	2‐(1‐Cyano‐2‐phenyl‐ethen‐1‐yl)‐5‐phenyl‐1,3,4‐
oxadiazole	(19)	

	
A	 solution	 of	 (18)	 (1	 g)	 in	 phosphorous	 oxychloride	 (20	

mL)	was	 heated	 on	water	 bath	 for	 4	 h.	 The	 reaction	mixture	
was	left	to	cool,	and	then	poured	with	stirring	into	crushed	ice.	
The	 solid	 separated	 out	 was	 filtered	 off,	 washed	 with	 water	
several	times,	dried	and	crystallized	from	ethanol	to	yield	19	as	
colourless	 crystals	 (Scheme	 1).	 Yield:	 40%.	 M.p.:	 168‐170	 oC.	
FT‐IR	 (KBr,	 cm‐1):	 2222	(CN).	 1H	NMR	 (300	MHz,	DMSO‐d6):	
7.62‐8.15	(m,	10H,	Ar‐H),	8.53	(s,	1H,	=CH).	MS	(EI,	m/z):	273	
(M.+).	 Anal.	 Calcd.	 for	 C17H11N3O:	 C,	 74.72;	 H,	 4.02;	 N,	 15.38.	
Found:	C,	74.98;	H,	4.22;	N,	15.46%.	
	
2.13.	2‐(1‐Cyano‐2‐phenyl‐ethen‐1‐yl)benzo[d]oxazole	(21)	

	
A	solution	of	20	(1	g)	in	phosphorous	oxychloride	(20	mL)	

was	heated	on	water	bath	for	8	h.	The	reaction	mixture	was	left	
to	 cool,	 and	 then	 poured	 into	 crushed	 ice.	 The	 solid,	 which	
separated	 out,	was	 filtered,	washed	with	water	 several	 times,	
dried	 and	 crystallized	 from	 benzene	 to	 afford	 21	 as	 yellow	
crystals	 (Scheme	1).	Yield:	40%.	M.p.:	140‐142	oC.	FT‐IR	(KBr,	
cm‐1):	2226	(CN).	1H	NMR	(300	MHz,	DMSO‐	DMSO‐d6):	7.47‐
8.03	(m,	9	H,	Ar‐H),	8.52	(s,	1H,	=CH).	MS	(EI,	m/z):	246	(M.+).	
Anal.	Calcd.	for	C16H10N2O:	C,	78.04;	H,	4.06;	N,	11.38.	Found:	C,	
78.11;	H,	3.77;	N,	11.51%.	

	
3.	Results	and	discussions	

	
Condensation	 of	 1	 with	 benzylamine	 or	 p‐anisidine	 in	

presence	 of	 triethylamine	 afforded	 the	 corresponding	 2‐
propenoylamides	 (2	 and	 3).	 Treatment	 of	 3	 with	 anhydrous	
aluminium	 chloride	 in	 benzene	 or	 chlorobenzene	 gave	 the	
corresponding	unexpected	demethylated	derivative	(4)	instead	
of	the	expected	quinolinone	derivative	[23]	(A)	(Scheme	1).	

Esterification	 of	 1	 with	 o‐cresol	 and	 p‐thiocresol	 yielded	
the	 ester	 and	 thioester	 (5	 and	 6)	 (Scheme	 1).	 On	 the	 other	
hand,	 condensation	 of	 1	 with	 ethanolamine	 gave	 the	 disubs‐
tituted	derivative	(7).	

Furthermore,	 reaction	 of	 1	 with	 o‐	 phenylenediamine	
afforded	 the	 corresponding	 diamide	 (8)	which,	 on	 treatment	
with	 POCl3	 or	 heating	 at	 its	 melting	 point,	 failed	 to	 give	 the	
expected	benzimidazole	derivative	(B)	[18]	(Scheme	1).	

The	condensation	product	of	reaction	of	1	with	anthranilic	
acid	depends	upon	both	the	base	used	and	reaction	conditions.	
In	presence	of	triethylamine	or	pyridine	at	room	temperature,	
the	authors	obtained	the	amide	(9),	which	upon	treatment	with	
acetic	 anhydride	 underwent	 cyclization	 to	 the	 benzoxazinone	
derivative	 (10)	 that	 upon	 heating	with	 ammonium	 acetate	 at	
140‐160	 oC	 without	 solvent	 afforded	 the	 corresponding	
quinazolinone	derivative	(11)	(Scheme	1).		

On	 the	 other	 hand,	 in	 presence	 of	 pyridine	 at	 refluxing	
temperature,	 a	 mixture	 of	 quinazolinone	 derivative	 (12)	 and	
benzamide	 derivative	 (13)	 was	 obtained.	 The	 reaction	
probably	 proceeded	 via	 the	 formation	 of	 benzoxazinone	 (10)	
followed	by	further	addition	of	anthranilic	acid	molecule	to	give	
(13)	 which	 underwent	 cyclization	 under	 the	 reaction	
conditions	 to	 afford	 the	 quinazolinone	 (12)	 (Scheme	 1,	 route	
a).	



204	 Shiba	et	al.	/	European	Journal	of	Chemistry	2	(2)	(2011)	200‐205	
	

	 	

 
	

Scheme	2
		
	

 
	

Scheme	3
		

	
The	 previous	 pathway	 was	 confirmed	 by	 reaction	 of	

benzoxazinone	(10)	with	anthranilic	acid	 in	ethanol	 to	yield	a	
mixture	 of	 12:13	 in	 10:90%	 yield,	 respectively,	 while	 upon	
heating	 compound	 10	 with	 anthranilic	 acid	 at	 140‐150	 oC	 in	
absence	of	solvent,	the	mixture	12:13	was	obtained	in	80:20	%	
yield,	respectively	(Scheme	1).	

Furthermore,	 refluxing	 benzamide	 derivative	 (13)	 in	
freshly	 distilled	 acetic	 anhydride	 yielded	 a	 mixture	 of	
benzoxazinone	 derivative	 (14)	 besides	 benzoxazinone	 (10)	
and	 quinazolinone	 (12)	 in	 45:5:25%	 yield	 via	 the	 available	
cyclization	 in	 route	 (a)	 or	 (b)	 to	 give	 12	 and	 14	 and/or	
unexpected	addition	via	route	(a)	with	subsequent	cleavage	of	
anthranilic	acid	moiety	to	give	10	(Scheme	1).	

Hydrazinolysis	 of	 benzoxazinone	 (10)	 with	 hydrazine	
hydrate	 in	refluxing	ethanol	afforded	 the	hydrazide	derivative	
15	 (Scheme	 1),	 which	 probably	 produced	 according	 to	 the	
plausible	mechanism	shown	in	Scheme	2.	

With	 2‐aminopyridine,	 acid	 chloride	 (1)	 gave	 the	 fused	
bicyclic	 system	 pyrido[1,2‐a]	 pyrimidine	 derivative	 (16)	
(Scheme	 1).	 The	 formation	 of	 pyridopyrimidine	 16	 can	 be	
interpreted	 as	 shown	 in	 (Scheme	 3)	 through	 normal	
substitution	 by	 tetrahedral	 mechanism	 on	 the	 carbonyl	
functionality	 of	 compound	1	 followed	by	 1,3‐proton	 shift	 and	
addition	 to	 ‐unsaturated	 nitrile	 with	 subsequent	
dehydrogenation	[24]	under	the	reaction	conditions,	according	
to	the	pathway	shown	in	Scheme	3.	

Reaction	 of	 chloride	 (1)	with	 2‐aminothiophenol	 gave	 the	
benzo‐1,5‐thiazepinone	 derivative	 (17)	 (Scheme	 1)	 whereas	
the	 treatment	 of	 1	 with	 benzoylhydrazine	 afforded	 the	
corresponding	 hydrazide	 derivative	 (18)	 which	 on	 heating	
with	POCl3	gave	the	oxadiazole	derivative	19.	

With	 2‐aminophenol,	 the	 isolated	 product	 was	 the	 amide	
derivative	(20)	which	was	dehydrated	under	the	effect	of	POCl3	
to	give	the	benzoxazole	derivative.	

4.	Conclusion	
	
(E)2‐Cyano‐3‐phenyl‐2‐propenoyl	 chloride	 could	 be	

utilized	 in	 the	 synthesis	 of	 some	 heterocyclic	 systems	 like	
benzoxazinone,	 quinazolinone,	 pyridopyrimidine,	 benzothi‐
azepine,	oxadiazole	and	benzoxazole	via	2‐propenoylamides	as	
intermediates.	

	
Acknowledgement	

	
Technical	 support	 from	Department	 of	 Chemistry,	 Faculty	

of	Science,	Ain	Shams	University	is	gratefully	acknowledged.		
	

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