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European	Journal	of	Chemistry	3	(1)	(2012)	65‐70	

European	Journal	of	Chemistry	
ISSN	2153‐2249	(Print)	/	ISSN	2153‐2257	(Online)		2012	EURJCHEM	

DOI:10.5155/eurjchem.3.1.65‐70.518	

	
	

	

	

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

	 	 	

Synthesis	of	novel	2‐propenoyl	amides,	esters,	heterocyclic	compounds	and	
their	screening	as	antifungal	and	antibacterial	agents	

Ahmed	El‐Ziatya,*,	Abdelaal	Abdalha,	Ashraf	Hameda,	Sayed	Shibab	and	Abdelhafed	Abdullhaa	

a	Chemistry	Department,	Faculty	of	Science,	Ain	Shams	University,	Abbassia	11566,	Cairo,	Egypt	
b	Chemistry	Department,	Faculty	of	Science	and	Hummanities,	Shaqra	University,	11962,	Harmala,	Saudia	Arabia	

*Corresponding	author	at:	Chemistry	Department,	Faculty	of	Science,	Ain	Shams	University,	Abbassia	11566,	Cairo,	Egypt.		
Tel.:	+202.2.4831836;	fax:	+202.2.4831836.	E‐mail	address:	ahm512@sci.asu.edu.eg	(A.	El‐Ziaty).	

	
	

	 	

	 	 	
ARTICLE	INFORMATION	 	 ABSTRACT
Received:	03	September	2011	
Received	in	revised	form:	26	September	2011	
Accepted:	26	September	2011	
Online:	31	March	2012	

KEYWORDS	

	 Compound,	 2‐cyano‐3‐(2ˊ,4ˊ‐dichlorophenyl)‐2‐prpoenoyl	 chloride,	 3,	 was	 reacted	 with
nitrogen,	sulfur,	 and	oxygen	nucleophilic	reagents	 to	give	new	2‐propenoyl	amide	and	ester
derivatives.	 Some	 of	 these	 derivatives	 were	 cyclized	 under	 the	 reaction	 conditions	 and/or
with	POCl3	or	Ac2O	to	give	new	derivatives	of	heterocyclic	systems.	Some	of	these	compounds
were	tested	as	antibacterial	and	antifungal	agents.	

Oxadiazole	
Benzoxazinone		
Pyridopyrimidine	
2‐Propenoyl	amide	
2‐Propenoyl	chloride	
Antibacterial	activities	

	
1.	Introduction	
	

The	recent	wide	importance	of	2‐propenoylamides	[1,2],	2‐
propenoates	 [3‐6],	 besides,	 the	 interesting	 biological	 and	
pharmacological	 activities	 of	 many	 heterocyclic	 systems,	 like,	
benzoxazoles	 [7],	 pyrimidines	 [8],	 pyridopyrimidines	 [9],	
oxazoles	 [10],	 benzoxazines	 [11,12],	 oxadiazoles	 [13]	 and	
pyrazoles	[14]	encourage	the	authors	to	gather	these	moieties	
hoping	 to	 produce	 a	 valuable	 new	 compounds	 of	 expected	
antibacterial	 and	 antifungal	 activity.	 We	 report	 here	 the	
synthesis	of	2‐propenoyl	amides,	2‐propenoyl	esters	and	some	
heterocyclic	 systems	 by	 developed,	 simple	 convenient	 and	
efficient	 procedure.	 Also	 this	 modified	 method	 is	 fast,	 cheap	
and	unequivocal	preparation	with	improved	yields.	
	
2.	Experimental	
	
2.1.	Instrumentation	
	

Melting	 points	 were	 taken	 on	 Griffin	 and	 Geory	 melting	
point	 apparatus	 and	 are	 uncorrected.	 FT‐IR	 spectra	 were	
recorded	on	Pye	Unicam	SP	1200	spectrophotometer	using	the	
KBr	 wafer	 technique.	 1H	 NMR	 spectra	 were	 determined	 on	
Varian	 Gemini	 300	 MHz	 using	 TMS	 as	 internal	 standard.	 All	
chemical	 shifts	 (δ)	 are	 expressed	 in	 ppm.	 All	 the	 NH	 or	 OH	
protons	 are	 exchangeable	 on	 addition	 of	 D2O.	 The	 elemental	
analyses	were	investigated	by	Elemental	analyzer	Vario	EL	III.	
	
2.2.	Syntheses	
	
2.2.1.	2‐cyano‐3‐(2ˊ,4ˊ‐dichlorophenyl)acryloyl	chloride	(3)	

	
A	 mixture	 of	 2	 (10	 g)	 and	 thionyl	 chloride	 (15	 mL)	 was	

heated	on	water	bath	 for	3	hours.	The	excess	 thionyl	chloride	

was	distilled	under	reduced	pressure;	 the	solid	separated	was	
collected,	 triturated	with	petroleum	ether	40‐60	C,	dried	and	
recrystallized	from	benzene	to	give	3	(Scheme	1).	Yellow.	Yield:	
90%.	 M.p.:	 88‐90	 oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 2205	 (C≡N),	 1738	
(C=O).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	8.39	(s,	1H,	=CH),	
8.04	(d,	1H,	J	=	8.4	Hz,	Ar‐H),	7.77	(s,	1H,	Ar‐H)	7.60	(d,	1H,	J	=	
8.4	Hz,	Ar‐H).	Anal.	calcd.	 for	C10H4Cl3NO:	C,	46.42;	H,	1.55;	N,	
5.38.	Found:	C,	45.89;	H,	1.51;	N,	5.34%.	
	
2.2.2.	General	procedure	for	the	formation	of	compounds	4‐9	
	

A	mixture	of	3	 (1.30	g,	0.005	mol),	 triethylamine	(0.505	g,	
0.005	mol),	and	phenol,	4‐chlorothiophenol,	4‐methoxyaniline,	
4‐chloroaniline,	 4‐methylaniline	 (0.005	 mol)	 in	 dry	 benzene	
(50	 mL)	 was	 refluxed	 for	 2	 hours.	 The	 solid	 separated	 was	
filtered,	washed	with	water	 (80	mL),	 dried	 and	 recrystallized	
from	toluene	to	give	4‐9,	respectively	(Scheme	2).	

Phenyl	 2‐cyano‐3‐(2,4‐dichlorophenyl)	 acrylate	 (4):	 Yellow.	
Yield:	75%.	M.p.:	120‐122	oC.	FT‐IR	(KBr,	ν,	cm‐1):	2232	(C≡N),	
1743	(C=O).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	8.37	(s	1H,	
=CH),	8.16	(d,	1H,	 J	=	8.4	Hz,	Ar‐H),	7.98	 (s,	1H,	Ar‐H)	7.75	(d,	
1H,	 J	=	8.4	Hz,	Ar‐H),	 7.75‐7.12	 (m,	 5H,	Ar‐H).	 Anal.	 calcd.	 for	
C16H9Cl2NO2:	C,	60.40;	H,	2.85;	N,	4.40.	Found:	C,	60.44;	H,	2.81;	
N,	3.92%.	

S(4‐Chlorophenyl)‐2‐cyano‐3‐(2,4‐dichlorophenyl)	 prop‐2‐
enethioate	 (5):	 Yellow.	 Yield:	 82%.	M.p.:	 162‐163	 oC.	 1H	 NMR	
(300	MHz,	DMSO‐d6,	δ,	ppm):	8.34	(s,	1H,	=CH),	8.03	(d,	1H,	J	=	
8.4	Hz,	Ar‐H),	7.83	(s,	1H,	Ar‐H),	7.62	(d,	1H,	 J	=	8.4	Hz,	Ar‐H),	
7.62‐7.02	(m,	4H,	Ar‐H).	Anal.	calcd.	for	C16H8Cl3NOS:	C,	52.13;	
H,	2.19;	N,	3.80.	Found:	C,	52.15;	H,	2.22;	N,	3.84%.	

2‐Cyano‐3‐(2,4‐dichlorophenyl)‐N‐(4‐methoxyphenyl)	
acrylamide	 (6):	 Yellow.	 Yield:	 80%.	 M.p.:	 218‐220	 oC.	 FT‐IR	
(KBr,	ν,	cm‐1):	3355	(NH),	2222	(C≡N),	1686	(C=O).		
	



66	 El‐Ziaty	et	al.	/	European	Journal	of	Chemistry	3	(1)	(2012)	65‐70	
	

 

 
Scheme	1

	
	
1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	10.35	(s,	1H,	NH),	8.36	(s,	
1H,	=CH),	8.06	(d,	1H,	J	=	8.4	Hz,	Ar‐H),	7.88	(s,	1H,	Ar‐H),	7.69	
(d,	1H,	J	=	8.4	Hz,	Ar‐H),	7.58	(d,	2H,	J	=	8.4	Hz,	Ar‐H),	6.9	(d,	2H,	
J	=	8.4,	Ar‐H),	3.74	(s,	3H,	OCH3).	Anal.	calcd.	for	C17H12Cl2N2O2:	
C,	58.81;	H,	3.48;	N,	8.07.	Found:	C,	58.85;	H,	3.56;	N,	7.98%.	

2‐Cyano‐3‐(2,4‐dichlorophenyl)‐N‐4‐tolylacrylamide	 (7):	
Yellow.	Yield:	90%.	M.p.:	198‐200	oC.	FT‐IR	(KBr,	ν,	cm‐1):	3342	
(NH),	2217	(C≡N),	1682	(C=O).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	
ppm):	10.42	(s,	1H,	NH),	8.36	(s,	1H,	=CH),	8.0	(d,	1H,	J	=	8.4	Hz,	
Ar‐H),	7.89	(s,	1H,	Ar‐H),	7.69	(d,	1H,	J	=	8.4	Hz,	Ar‐H),	7.55	(d,	
2H,	J	=	8.4	Hz,	Ar‐H),	7.18	(d,	2H,	J	=	8.4	Hz,	Ar‐H),	2.39	(s,	3H,	
CH3).	 Anal.	 calcd.	 for	 C17H12Cl2N2O:	 C,	 61.65;	 H,	 3.65;	 N,	 8.46.	
Found:	C,	61.60;	H,	3.67;	N,	8.12%.	

N‐(4‐chlorophenyl)‐2‐cyano‐3‐(2,4‐dichlorophenyl)	
acrylamide	 (8):	 Yellow.	 Yield:	 80%.	 M.p.:	 158‐159	 oC.	 FT‐IR	
(KBr,	 ν,	 cm‐1):	 3323	 (NH),	 2228	 (C≡N),	 1687	 (C=O).	 1H	 NMR	
(300	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 10.64	 (s,	 1H,	 NH),	 8.39	 (s	 1H,	
=CH),	8.06	(d,	1H,	 J	=	8.4	Hz,	Ar‐H),	7.89	(s,	1H,	Ar‐H),	7.72	(d,	
1H,	 J	=	8.4	Hz,	Ar‐H),	 7.70‐7.42	 (m,	 4H,	Ar‐H).	 Anal.	 calcd.	 for	
C16H9Cl3N2O:	C,	54.65;	H,	2.58;	N,	7.97.	Found:	C,	54.61;	H,	2.62;	
N,	8.10%.	

2‐Cyano‐3‐(2,4‐dichlorophenyl)‐N‐(pyridine‐3‐yl)	acrylamide	
(9):	Yellow.	Yield:	75%.	M.p.:	176‐178	oC.	FT‐IR	(KBr,	ν,	cm‐1):	
3338	(NH),	2225	(C≡N),	1692	(C=O).	1H	NMR	(300	MHz,	DMSO‐
d6,	δ,	ppm):	9.64	(s,	1H,	NH),	8.42	(s	1H,	=CH),	8.09	(d,	1H,	J	=	
8.4	Hz,	Ar‐H),	7.98	(s,	1H,	Ar‐H),	7.70	(d,	1H,	 J	=	8.4	Hz,	Ar‐H),	
7.70‐7.42	(m,	4H,	Ar‐H).	Anal.	 calcd.	 for	C15H9Cl2N3O:	C,	56.63;	
H,	2.85;	N,	13.21.	Found:	C,	56.59;	H,	2.79;	N,	13.02%.	
	
2.2.3.	N’‐(2‐Cyano‐3‐(2,4‐dichlorophenyl)acryloyl)	
benzohydrazide	(10)	
	

A	mixture	of	3	 (1.30	g,	0.005	mol),	 triethylamine	(0.505	g,	
0.005	mol)	 and	 benzoyl	 hydrazine	 (0.68	 g,	 0.005	mol)	 in	 dry	
benzene	 (50	mL)	was	 stired	 for	 an	 hour.	 The	 solid	 separated	
was	 filtered,	 washed	 with	 water	 (80	 mL),	 dried	 and	
recrystallized	 from	 toluene	 to	 give	 10	 (Scheme	 2).	 Yellow.	
Yield:	86%.	M.p.:	180‐181	oC.	FT‐IR	(KBr,	ν,	 cm‐1):	3188,	3209	
(NH),	2218	(C≡N),	1675	(C=O).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	
ppm):	 10.81	 (s,	 1H,	NH),	 10.64	 (s,	 1H,	NH),	 8.4	 (s,	 1H,	 =CH),	
7.89‐7.49	(m,	8H	Ar‐H).	Anal.	calcd.	for	C17H11Cl2N3O2:	C,	56.69;	
H,	3.08;	N,	11.67.	Found:	C,	56.65;	H,	2.99;	N,	11.61%.	
	
2.2.4.	(E)‐3‐(2,4‐ichlorophenyl)‐2‐(5‐phenyl‐1,3,4‐oxadiazol‐
2‐yl)acrylonitrile	(11)	
	

A	mixture	of	10	(1	g)	and	phosphorus	oxychloride	(10	mL)	
was	 heated	 on	 water	 bath	 for	 6	 hours.	 After	 cooling	 the	
reaction	mixture	was	poured	on	 crushed	 ice	 (20	g).	The	 solid	
separated	was	filtered,	washed	with	water	(50	mL),	dried	and	
recrystallized	ftom	ethanol	to	give	11	(Scheme	2).	Green.	Yield:	

75%.	 M.p.:	 176‐178	 oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 2205	 (C≡N).	 1H	
NMR	(300	MHz,	CDCl3,	δ,	ppm):	8.56	(s,	1H,	Ar‐H)	8.27	(d,	1H,	J	
=	8.4	Hz,	Ar‐H),	8.14	(d,	1H,	J	=	8.1	Hz,	Ar‐H),	7.54‐7.43	(m,	6H,	
Ar‐H,	5ph+1aryl).	Anal.	calcd.	for	C17H9Cl2N3O:	C,	59.67;	H,	2.65;	
N,	12.28.	Found:	C,	59.72;	H,	2.61;	N,	12.33%.	
	
2.2.5.	6‐(2,4‐Dichlorophenyl)‐4‐hydroxy‐1‐methyl‐2‐thioxo‐
1,2‐dihydropyrimidine‐	5‐carbonitrile	(12)	
	

N‐methylthiourea	 (0.45	 g,	 0.005	 mol)	 was	 added	 to	 a	
solution	of	3	 (1.30	g,	0.005	mol)	 in	dry	benzene	 (50	mL)	and	
triethylamine	 (0.505	 g,	 0.005	mol),	 the	 reaction	 mixture	 was	
refluxed	for	one	hour.	The	solid	formed	was	collected,	washed	
with	water	 (80	mL),	 dried	 and	 recrystallized	 from	 ethanol	 to	
give	12	(Scheme	2).	Yellow.	Yield:	80%.	M.p.:	186‐188	oC.	FT‐IR	
(KBr,	 ν,	 cm‐1):	 3449	 (OH),	 2211	 (CN),	 1633	 (C=N).	 1H	 NMR	
(300	MHz,	DMSO‐d6,	δ,	ppm):	7.9	(d,	1H,	J	=	7.9	Hz,	Ar‐H),	7.8	(d,	
1H,	J	=	7.8	Hz,	Ar‐H),	7.76	(s,	1H,	Ar‐H),	3.79	(s,	3H,	NCH3),	1.6	
(s,	1H,	OH).	Anal.	 calcd.	 for	C12H7Cl2N3OS:	C,	 46.17;	H,	2.26;	N,	
13.46.	Found:	C,	45.81;	H,	2.81;	N,	13.43%.	
	
2.2.6.	1‐(2‐Cyano‐3‐(2,4‐dichlorophenyl)acryloyl)‐3‐
phenylurea	(13)	
	

A	mixture	of	3	 (1.30	g,	0.005	mol),	 triethylamine	(0.505	g,	
0.005	 mol)	 and	 phenylurea	 (0.681	 g),	 0.005	 mol)	 in	 dry	
benzene	(50	mL)	was	stirred	 for	2	hours.	The	separated	solid	
was	 filtered,	 washed	 with	 water	 (80	 mL),	 dried	 and	
recrystallized	 from	 benzene	 to	 give	 13	 (Scheme	 2).	 Yellow.	
Yield:	60%.	M.p.:	180‐181	oC.	FT‐IR	(KBr,	ν,	cm‐1):	3231,	3129	
(NH),	 2228	 (C≡N),	 1704,	 1660	 (C=O).	 1H	 NMR	 (300	 MHz,	
DMSO‐d6,	δ,	ppm):	10.23	(s,	1H,	NH,),	8.5	(s,	1H,	=CH),	8.06‐6.53	
(m,	8H,	Ar‐H),	5.8	(s,	1H,	NH).	Anal.	calcd.	for	C17H11Cl2N3O2:	C,	
56.69;	H,	3.08;	N,	11.67.	Found:	C,	56.62;	H,	3.12;	N,	11.59%.	
	
2.2.7.	Synthesis	of	compounds	14	and	15		
	

A	mixture	of	3	 (1.30	g,	0.005	mol),	 triethylamine	(0.505	g,	
0.005	 mol)	 and	 2‐aminopyridine	 (0.47	 g,	 0.005	 mol)	 in	 dry	
benzene	(50	mL)	was	stirred	 for	2	hours.	The	separated	solid	
was	filtered,	washed	with	water,	dried	and	recrystallized	from	
benzene	to	give	14	and	then	from	ethanol	to	give	15	 (Scheme	
2).	

2‐Cyano‐3‐(2,4‐dichlorophenyl)‐N‐(pyridin‐2‐yl)	 acrylamide	
(14):	Yellow.	Yield:	90%.	M.p.:	210‐211	oC.	FT‐IR	(KBr,	ν,	cm‐1):	
3305	 (NH),	 2216	 (C≡N),	 1669	 (C=O).	 1H‐NMR	 (300	 MHz,	
DMSO‐d6,	δ,	ppm):	8.3	(s,	1H,	=CH),	8.07	(d,	1H,	J	=	8.4	Hz,	Ar‐H),	
6.03	(m,	3H,	Ar‐H),	7.6	(s,	1H,	NH)	6.7‐6.6	(m,	3H,	Ar‐H).	Anal.	
calcd.	 for	 C15H9Cl2N3O:	 C,	 56.63;	 H,	 2.85;	 N,	 13.21.	 Found:	 C,	
56.59;	H,	2.89;	N,	13.28%.	

	



El‐Ziaty	et	al.	/	European	Journal	of	Chemistry	3	(1)	(2012)	65‐70	 67	
 

	

3

Ar

H

Cl

O

CN

Ar

H

X

O

NC

Ar/

4, X = O; Ar/ = C6H5
5, X = S; Ar/ = C6H4(4-Cl)

6, X = NH; Ar/ = C6H4(P-OCH3)

7, X = NH; Ar/ = C6H4(P-CH3)

8, X = NH;.Ar/ = C6H4 (P-Cl)

9, X = NH; Ar/ = 3-Pyridyl

4-9

Ph
CO
NH
NH

2

Ar

H

N
H

O

CN

10

PO
Cl 3

NN

O
Ph

NC
11

Ar

H

NH
2CSNHCH

3

2-aminpryidine

N

N

OH

NC

Ar

CH3

S

12

Ar

H

N
H

O

CN

O

13

Ar

H

CN

O

N
H

N

14

+

N

N

Ar

NC

HO

15

Ar = C6H3Cl2(2,4)

N
H

Ph

H
N Ph

O

 
	

Scheme	2	
	
	
4‐(2,4‐dichlorophenyl)‐2‐hydroxy‐4H‐pyrimido[1,2‐a]	

pyrimidine‐3‐carbonitrile	 (15):	 Yellow.	 Yield:	 65%.	 M.p.:	 152‐
153	 oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 3444	 (NH),	 2186	 (C≡N),	 1681	
(C=O).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	9.63	(s,	1H,	OH),	
8.56	 (d,	 1H,	 J	=	6.9	Hz,	Ar‐H),	 7.8‐6.8	 (m,	 6H,	Ar‐H),	 5.9	 (s,	H,	
benzylic	H).	 Anal.	 calcd.	 for	 C15H9Cl2N3O:	 C,	 56.63;	 H,	 2.85;	 N,	
13.21.	Found:	C,	56.56;	H,	2.93;	N,	13.21%.	
	
2.2.8.	Synthesis	of	compounds	16	and	17		
	

Thiosemicarbazide	 (0.45	 g,	 0.005	 mol)	 was	 added	 to	 a	
solution	 of	 3	 (1.30	 g,	 0.005	 mol)	 in	 dioxane	 (20	 mL)	 and	
triethylamine	 (0.505	 g,	 0.005	mol).	 The	 reaction	mixture	was	
refluxed	for	an	hour.	The	solid	formed	was	ammonium	salt,	the	
filtrate	 was	 concentrated,	 and	 the	 remaining	 semisolid	 was	
recrystallized	 from	 benzene	 to	 give	 16	 and	 then	 from	
benzene/ethanol	mixture	to	give	17	(Scheme	3)	

1‐(2,4‐Dichlorobenzylidene)thiosemicarbazide	 (16)	 the	
structure	was	confirmed	by	m.p.	with	an	authentic	sample	[15].		

4‐(2,4‐dichlorobenzylidene)‐3‐amino‐1H‐pyrazol‐5‐(4H)‐one	
(17):	Reddish	brown.	Yield:	84%.	M.p.:	150‐151	oC.	FT‐IR	(KBr,	
ν,	cm‐1):	3179,	3263,	3369	(NH,	NH2),	1645	(C=O),	1619(C=N).	
1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	8.54	(s,	1H,	NH),	8.35	(s,	
1H,	=CH),	7.4‐7.2	(m,	3H,	Ar‐H),	4.4	(s,	2H,	NH2).	Anal.	calcd.	for	
C10H7Cl2N3O:	 C,	 46.90;	 H,	 2.76;	 N,	 16.41.	 Found:	 C,	 46.85;	 H,	
2.71;	N,	16.38%.	
	

2.2.9.	3‐(2,4‐Dichlorophenyl)‐2‐(4,5‐dihydrooxazol‐2‐yl)	
acrylonitrile	(18)	
	

A	mixture	of	3	 (1.30	g,	0.005	mol),	 triethylamine	(0.505	g,	
0.005	 mol)	 and	 ethanolamine	 (0.305	 g,	 0.005	 mol)	 in	 dry	
benzene	(50	mL)	was	stirred	 for	2	hours.	The	separated	solid	
was	 filtered,	 washed	 with	 water	 (50	 mL),	 dried	 and	
recrystallized	 from	 ethanol	 to	 give	 18	 (Scheme	 3):	 Yellow.	
Yield:	90%.	M.p.:	220‐222	oC.	FT‐IR	(KBr,	ν,	cm‐1):	2209	(C≡N),	
1642	(C=N).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	7.77	(s,	1H,	
=CH),	7.69‐7.40	(m,	3H,	Ar‐H),	3.61	(t,	2H,	 J	=	6.90	Hz,	CH2‐O),	
1.84	(t,	2H,	J	=	6.90	Hz,	N‐CH2).	Anal.	calcd.	for	C12H8Cl2N2O:	C,	
53.96;	H,	3.02;	N,	10.49.	Found:	C,	53.89;	H,	2.98;	N,	10.51%.	
	
2.2.10.	2‐(2‐Cyano‐3‐(2,4‐dichlorophenyl)acrylamido)	
benzoic	acid	(19)		
	

A	 mixture	 of	 3	 (2.60	 g,	 0.01	 mol),	 triethylamine	 (1.01	 g,	
0.01	mol)	and	anthranilic	acid	(1.37	g,	0.01	mol)	in	dry	benzene	
(100	mL)	was	 refluxed	 for	 an	 hour.	 The	 solid	 separated	was	
filtered,	washed	with	water	(100	mL),	dried	and	recrystallized	
from	 benzento	 give	19	 (Scheme	 3):	 Brown.	 Yield:	 84%.	M.p.:	
172‐173	oC.	FT‐IR	(KBr,	ν,	cm‐1):	3359	(NH),	2220	(C≡N),	1689	
(C=O).	 1H	 NMR	 (300	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 10.75	 (s,	 1H,	
COOH),	8.39	(s,	1H,	=CH),	8.07‐7.94	 (m,	4H,	Ar‐H),	7.89	(s,	1H,	
NH),	7.81‐7.62	(m,	3H,	Ar‐H).	Anal.	 calcd.	 for	C17H10Cl2N2O3:	C,	
56.53;	H,	2.79;	N,	7.76.	Found:	C,	56.68;	H,	2.82;	N,	7.68%.	
	



68	 El‐Ziaty	et	al.	/	European	Journal	of	Chemistry	3	(1)	(2012)	65‐70	
	
	

N
H
2 N
H
C
S
N
H
2

an
th
ran

ilic
acid

 
	

Scheme	3
	

	
2.2.11.	3‐(2,4‐Dichlorophenyl)‐2‐(4‐oxo‐4H‐benzo[d][1,3]	
oxazin‐2‐yl)acrylonitrile	(20)	
	

A	mixture	of	19	(2	g)	and	freshly	distilled	acetic	anhydride	
(5	mL)	was	heated	on	a	water	bath	 for	6	hours.	After	 cooling	
the	solid	separated	was	collected,	washed	with	dry	petroleum	
ether	(40‐60	oC),	dried	and	recrystallized	from	ethanol	to	give	
20	 (Scheme	 3):	 Green	 .	 Yield:	 85%.	 M.p.:	 172‐173	 oC.	 FT‐IR	
(KBr,	 ν,	 cm‐1):	 2205	 (C≡N),	 1758	 (C=O).	 1H	 NMR	 (300	 MHz,	
DMSO‐d6,	 δ,	 ppm):	 8.52	 (s,	 1H,	=CH),	 8.21‐7.94	 (m,	 3H,	Ar‐H),	
7.93‐7.96	(m,	4H,	Ar‐H).	Anal.	calcd.	for	C17H8Cl2N2O2:	C,	59.50;	
H,	2.35;	N,	8.16.	Found:	C,	60.01;	H,	2.33;	N,	8.19%.	
	
2.2.12.	2‐Cyano‐3‐(2,4‐dichlorophenyl)‐N‐(2‐hydroxy	
phenyl)	acrylamide	(21)	
	

A	mixture	of	3	 (1.30	g,	0.005	mol),	 triethylamine	(0.505	g,	
0.005	 mol)	 and	 2‐amino	 phenol	 (0.54	 g,	 0.005	 mol)	 in	 dry	
benzene	(50	mL)	was	refluxed	for	an	hour.	The	solid	separated	
was	 filtered,	 washed	 with	 water	 (80	 mL),	 dried	 and	
recrystallized	from	toluene	to	give	21	(Scheme	3)	Yellow.	Yield:	
92%.	M.p.:	108‐110	 oC.	FT‐IR	 (KBr,	 ν,	 cm‐1):	3247,	3353	 (NH),	
2213	(C≡N),	1669	(C=O).	1H	NMR	(300	MHz,	DMSO‐d6,	δ,	ppm):	
10.15	(s,	1H,	NH),	9.4	 (s,	1H,	OH),	8.43	(s,	1H,	=CH),	8.10‐6.80	
(m,	7H,	Ar‐H).	Anal.	 calcd.	 for	C16H10Cl2N2O2:	C,	57.68;	H,	3.03;	
N,	8.41.	Found:	C,	57.56;	H,	2.98;	N,	8.32%.	
	
2.2.13.	2‐(Benzo[d]oxazol‐2‐yl)‐3‐(2,4‐dichlorophenyl)	
acrylonitrile	(22)	
	

A	mixture	of	21	(1	g)	and	phosphorus	oxychloride	(10	mL)	
was	 heated	 on	 water	 bath	 for	 6	 hours.	 After	 cooling	 the	
reaction	mixture	was	poured	on	 crushed	 ice	 (20	g).	The	 solid	
separated	was	filtered,	washed	with	water	(50	mL),	dried	and	
recrystallized	from	ethanol	to	give	22	(Scheme	3).	Green.	Yield:	
82%.	M.p.:	 150‐152	 oC.	 FT‐IR	 (KBr,	 ν,	 cm‐1):	 2205	 (C≡N)	 and	

1622	(C=N)	1H	NMR	(300	MHz,	DMSO‐d6,	 δ,	ppm):	8.6‐7.8	 (m,	
3H,	 Ar‐H),	 7.43‐	 7.40	 (m,	 4H,	 Ar‐H),	 7.25	 (s,	 1H,	 =CH).	 Anal.	
calcd.	 for	 C16H8Cl2N2O:	 C,	 60.98;	 H,	 2.56;	 N,	 8.89.	 Found:	 C,	
60.86;	H,	2.51;	N,	8.81%.	
	
2.3.	Antimicrobial	and	antifungal	activities		
	

A	 filter	 paper	 sterilized	 disc	 saturated	 with	 measured	
quantity	 of	 the	 sample	 with	 concentration	 of	 20	mg/mL	was	
placed	 on	 a	plate	 containing	 solid	 bacterial	medium	 (nutrient	
agar	 broth)	 or	 fungal	 medium	 (Dox’s	 medium)	 which	 was	
heavily	 seeded	 with	 the	 spore	 suspension	 of	 the	 tested	
organism.	 After	 incubation,	 the	 diameter	 of	 the	 clear	 zone	 of	
inhibition	 surrounding	 the	 sample	was	 taken	 as	 a	measure	of	
the	 inhibitory	power	of	 the	 sample	 against	 the	particular	 test	
organism	[16‐19].	

The	selected	samples	were	screened	against	Gram‐positive;	
Staphylococcus	 aureus	 and	 Gram‐negative	 Escherichia	 coli.	
Antifungal	 activity	 was	 tested	 using	 Aspergillus	 flavus	 and	
Candida	albicans	(Table	1).	
	
Table	 1.	 The	 antimicrobial	 and	 antifungal	 activities	 of	 the	 selected	
compounds*.	
Sample Escherichia	

coli	
Staphylococcus	
aureus	

Aspergillus	
flavus	

Candida	
albicans	

4	 13	 12	 0	 0	
5	 16	 20	 0	 0	
6 10 13 0	 0
7 13 13 0	 0
9 10 11 0	 0
10 17 15 0	 13
12 19 18 0	 12
17 13 15 0	 0
Tetracycline 32 30 ‐‐‐	 ‐‐‐
Amphotericin	
B	 ‐‐‐	 ‐‐‐	 16	 18	

DMSO	 0	 0	 0	 0	
*	 Solvent:	Chloroform;	 0:	 no	 activity	 (inhibition	 zone	 less	 than	7mm);	 7‐10	
weak	activity;	11‐15	moderate	activity;	more	than	15	strong	activity.	



El‐Ziaty	et	al.	/	European	Journal	of	Chemistry	3	(1)	(2012)	65‐70	 69	
 

	

H

Ar C

N

NH

O

S

HN

H3C

-H/+H

N NH

CN

Ar

H3C

S

O

N NH

CN

O

S

H3C

Ar

12

CN

H

Ar

COCl

H2N N
H

S

CH3

T.E.A
-HCl

3

-H2

N N

CN

OH

S

H3C

Ar

 
	

Scheme	4
	
	
	

 
	

Scheme	5
	
	
3.	Results	and	discussion	
	

In	 continuation	 of	 our	 efforts	 to	 study	 the	 reactivity	 of	 2‐
propenoyl	 chlorides	 towards	 some	 nitrogen	 and	 oxygen	
nucleophilic	 reagents	 [20‐23],	 we	 reported	 herein,	 the	
synthesis	 of	 a	 new	 compound,	 (E)2‐cyano‐3‐(2,4‐dichloro	
phenyl)acryloyl	chloride	3	via	the	common	route	condensation	
of	 2,4‐dichlorobenzaldehyde	 with	 ethyl	 cyanoacetate	 in	 the	
presence	 of	 piperidine,	 to	 give	 the	 corresponding	 (E)‐ethyl	 2‐
cyano‐3‐(2,4‐dichlorophenyl)	acrylate,	1,	 [24].	Hydrolysis	of	1	
in	alcoholic	solution	of	sodium	hydroxide	(1:1	mole)	gave	(E)‐
2‐cyano‐3‐(2,4‐dichlorophenyl)acrylic	 acid,	 2,	 [25].	 Refluxing	
the	 acid	 2	 with	 thionyl	 chloride	 yielded	 the	 new	 acryloyl	
chloride	derivative	3	in	good	yield	(Scheme	1).	

The	acryloyl	chloride	derivative	3	was	reacted	with	phenol,	
4‐chlorothiophenol	 and	 primary	 amines	 such	 as,	 4‐
methoxyaniline,	 4‐methylaniline4chloroaniline	 and	 3‐amino	
pyridine	in	dry	benzene	in	the	presence	of	triethylamine	to	give	
acrylate,	 thioacrylate	 and	 acrylamides,	 4‐9,	 respectively	
(Scheme	2).	

On	 the	 other	 hand,	 reaction	 of	 the	 acryloyl	 chloride	
derivative	 3	 with	 benzoyl	 hydrazine	 as	 a	 bifunctional	
nucleophile	 under	 the	 same	 conditions	 gave	 the	 benzoyl	
hydrazide	 derivative	 10	which	 underwent	 ring	 closure	 upon	

heating	 with	 POCl3	 to	 give	 the	 oxadiazole	 derivative	 11	
(Scheme	 2).	 When	 the	 acryloyl	 chloride	 derivative	 3	 was	
allowed	 to	 react	 with	 methylthiourea,	 phenylurea	 and	 2‐
aminopyridine	 as	 1,3‐binucleophilic	 reagents,	 it	 gave	 the	
tetrahydropyrimidine‐2‐thione	 derivative	 12,	 1‐acryloyl‐3‐
phenyl	 urea	 derivative	 13	 and	 a	 mixture	 of	 acrylamide	
derivative	14	and	pyridopyrimidine	derivative	15,	respectively	
(Scheme	2).	

The	formation	of	compound	12	can	be	represented	by	the	
following	pathway	(Scheme	4).	

The	 formation	of	 compounds	14	 and	15	can	be	explained	
by	the	following	pathway	(Scheme	5).	

When	 the	 acryloyl	 chloride	 derivative	 3	 was	 allowed	 to	
react	 with	 thiosemicarbazide,	 it	 gave	 a	 mixture	 of	 the	
thiosemicarbazone	 16	 and	 the	 pyrazolone	 derivative	 17	
(Scheme	 3).	 The	 acryloyl	 derivative	 3	 condensed	 with	
ethanolamine	 to	 give	 the	 dihydrooxazole	 derivative	 18	
(Scheme	 3).	 2‐Propenoyl	 amide	 19	 was	 prepared	 by	
condensation	 of	 3	 with	 anthranilic	 acid	 in	 the	 presence	 of	
triethylamine	 (TEA).	 The	 structure	 of	 19	 was	 confirmed	
chemically	by	ring	closure	using	acetic	anhydride	whereby	the	
benzoxazinone	20	was	obtained	(Scheme	3).		

	
	



70	 El‐Ziaty	et	al.	/	European	Journal	of	Chemistry	3	(1)	(2012)	65‐70	
	

	

N
H 2
N
H
C
S
N
H 2

 
	

Scheme	6
	
	
The	acrylamide	derivative	21,	which	was	prepared	by	 the	

reaction	 of	 3	 with	 2‐aminophenol,	 gave	 the	 benzoxazole	
derivative	 22	 upon	 heating	 with	 phosphorus	 oxychloride	
(Scheme	3).		

The	formation	of	compounds	16	and	17	can	be	represented	
by	the	following	pathway	Scheme	6.	
	
4.	Conclusion	
	

2‐Propenoyl	derivatives	and	some	heterocyclic	compounds	
with	 antibacterial	 and	 antifungal	 activities	 were	 synthesized	
from	 readily	 obtainable	 starting	materials	 such	 as	 2‐cyano‐3‐
(2ˊ,4ˊ‐dichlorophenyl)acryloyl	chloride,	3.	
	
Acknowledgements	
	

The	 best	 regards	 for	 the	 Micro	 Analytical	 Center,	 Cairo	
University,	 Egypt	 for	 carrying	out	 the	biological	 activities	 and	
spectral	studies	
	
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