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European	Journal	of	Chemistry	5	(4)	(2014)	570‐576	

	

European	Journal	of	Chemistry	
ISSN	2153‐2249	(Print)	/	ISSN	2153‐2257	(Online)		2014	Eurjchem	Publishing	‐	Printed	in	the	USA	

http://dx.doi.org/10.5155/eurjchem.5.4.570‐576.1098	

	
	

	

	

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

	 	 	

Synthesis,	characterization	and	in	vitro	biological	evaluation	of		
some	new	1,3,5‐triazine‐chalcone	hybrid	molecules	as		
Mycobacterium	tuberculosis	H37Rv	inhibitors	

Subbarayal	Reddy	Dwarampudi	a,*,	Gowri	Sankar	Dannana	a,		
Vasudeva	Rao	Avupati	b	and	Venkata	Satyanarayana	Murthy	Bendi	c	

a	Pharmaceutical	Analysis	and	Quality	Assurance	Division,	Andhra	University	College	of	Pharmaceutical	Sciences,	Andhra	University,	Visakhapatnam‐530003,	
Andhra	Pradesh,	India	
b	Pharmaceutical	Chemistry	Division,	Andhra	University	College	of	Pharmaceutical	Sciences,	Andhra	University,	Visakhapatnam‐530003,	Andhra	Pradesh,	India	
c	Pharmacology	Division,	Andhra	University	College	of	Pharmaceutical	Sciences,	Andhra	University,	Visakhapatnam‐530003,	Andhra	Pradesh,	India	

*Corresponding	author	at:	Pharmaceutical	Analysis	and	Quality	Assurance	Division,	Andhra	University	College	of	Pharmaceutical	Sciences,	Andhra	University,	
Visakhapatnam‐530003,	Andhra	Pradesh,	India.		
Tel.:	+91.94.40653159.	Fax:	+91.891.2755075.	E‐mail	address:	dwarampudisubbarayalreddy@gmail.com	(D.S.	Reddy).	

	
	

	 	

	 	 	
ARTICLE	INFORMATION	 	 ABSTRACT	

	
DOI:	10.5155/eurjchem.5.4.570‐576.1098	

Received:	05	June	2014	
Received	in	revised	form:	30	June	2014	
Accepted:	02	July	2014	
Online:	31	December	2014	

KEYWORDS	

	 A	novel	series	of	1,3,5‐triazine‐chalcone	hybrid	molecules	(4a‐ii)	have	been	synthesized	and
evaluated	in	vitro	for	Mycobacterium	tuberculosis	H37Rv	inhibitory	potency	using	Alamar	blue
assay	 and	 the	 activity	 expressed	 as	 the	minimum	 inhibitory	 concentration	 (MIC)	 in	 µg/mL.
The	 antitubercular	 activity	 screening	 data	 revealed	 that	 the	 compound	 4z	 demonstrated
comparatively	 the	 most	 potent	 inhibitory	 activity,	 with	 MIC	 value	 3.125	 µg/mL.	 It	 is
noteworthy	 that	 the	compounds	4e,	4p	and	4bb	also	showed	appreciable	 inhibitory	activity
with	MIC	value	6.25	µg/mL.	Most	of	the	compounds	displayed	significantly	promising	activity
and	 their	 structure‐activity	 relationships	were	also	discussed.	This	could	be	 the	 remarkable
starting	point	to	develop	new	lead	molecules	with	potential	antitubercular	activity.	

Hybrid	molecules		
Alamar	blue	assay	
1,3,5‐Triaizine‐chalcone	
Structure	activity	relationship	
Minimum	inhibitory	concentration	
Mycobacterium	tuberculosis	H37Rv	

	
1.	Introduction	
	

Tuberculosis	 (TB)	 remains	a	major	 global	health	problem.	
In	2012,	an	estimated	8.6	million	people	developed	TB	and	1.3	
million	died	from	the	disease	(including	320000	deaths	among	
HIV‐positive	 people)	 [1].	 It	 is	 caused	 by	 several	 species	 of	
Mycobacteria	including	Mycobacterium	tuberculosis,	M.	bovis,	M.	
africanum,	M.	microti,	M.	 leprae	 and	M.	 avium	 that	 are	 intra‐
cellular,	 Gram‐positive,	 non‐motile,	 and	 rod‐shaped	 obligate	
aerobic	 pathogens	 of	 higher	 vertebrates	 [2].	 Although	 this	
disease	can	be	cured	with	the	current	therapy,	 the	treatments	
require	six	to	nine	months	of	time	period	that	is	too	 long,	and	
accompanied	 by	 significant	 toxicity	 [3].	 These	 factors	 make	
patient	 compliance	 to	 therapy	 very	 difficult,	 and	 this	
noncompliance	 frequently	 selects	 for	 drug‐resistant	 TB	
bacteria	 [4].	 An	 increasing	 occurrence	 of	 deaths	 due	 to	
tuberculosis	and	the	known	drawbacks	of	the	current	existing	
drugs	 including	 the	 emergence	of	multi	 drug‐resistant	 strains	
have	 led	 to	 a	 renewed	 interest	 in	 the	 discovery	 of	 new	 anti‐
tubercular	agents	with	novel	modes	of	actions	[5].	The	topical	

researches	focused	on	new	synthetic	products	that	have	shown	
a	 useful	 way	 to	 obtain	 a	 potentially	 rich	 source	 of	 drug	
candidates	[6‐9].	

In	 recent	 past,	 2,4,6‐trisubstituted‐1,3,5‐triazine	 scaffolds	
were	 discovered	 as	 a	 potent	 inhibitors	 of	 Mycobacterium	
tuberculosis	(Mtb)	H37Rv	[10].	Currently	1,3,5‐triazine	deriva‐
tives	 have	 been	 found	 to	 possess	 wide	 range	 of	 biological	
activities,	 such	 as	 adenosine	 receptor	 antagonist	 [11],	 anti‐
amoebic	 [12],	 anticancer	 [13],	 antileishmanial	 [14],	 antima‐
larial	 [15],	 antimicrobial	 [16],	 antiviral	 [17],	 antitubercular	
[18],	 carbonic	 anhydrase	 inhibitor	 [19],	 cathepsin	 B	 inhibitor	
[20],	cholesteryl	ester	 transfer	protein	 inhibitor	 [21],	corticot‐
ropin‐releasing	factor	ligand	[22],	CRF1	PET	imaging	agent	[23],	
cytosolic	phospholipase	A2α	inhibitor	[24],	dipeptidyl	peptidase	
IV	inhibitor	[25],	bacterial	enzyme	DNA	helicase	inhibitor	[26],	
dual	 PI3/mTOR	 inhibitor	 [27],	 glucocerebrosidase	 inhibitor	
[28],	α‐glucosidase	inhibitor	[29],	growth	factor	inhibitor	[30],	
human	 gonadotropin‐releasing	 hormone	 receptor	 antagonist	
[31],	 5‐HT7	 receptor	 antagonist	 [32],	 inosine	monophosphate	
dehydrogenase	inhibitor	[33],	mTOR	kinase	inhibitor	[34],		



Dwarampudi	et	al.	/	European	Journal	of	Chemistry	5	(4)	(2014)	570‐576	 571	
 

	

	
	

Scheme	1	
	
	
voltage‐gated	sodium	channel	Nav	1.7	antagonist	[35],	neuronal	
voltage‐gated	sodium	channel	blocker	[36],	phosphodiesterase	
type	4	 inhibitor	 [37],	protein	kinase	CK2	 inhibitor	 [38],	ROCK	
inhibitor	 [39],	 β‐secretase	 inhibitor	 [40],	 sorbitol	 dehydroge‐
nase	inhibitor	[41],	tryptophan	hydroxylase	 inhibitor	[42]	and	
VLA‐4	 integrin	 antagonist	 [43].	 Similarly,	 azomethine	 moiety	
has	 gained	 a	 great	 importance,	 since	 it	 has	 been	 found	 to	
possess	several	biological	activities,	such	as	antimicrobial	[44‐
47],	 antiviral	 [48,49],	 antioxidant	 [50],	 radical	 inhibitor	 [51],	
antitumor	[52,53],	carbonic	anhydrase	inhibitor	[54],	xanthine	
oxidase	 inhibitor	 [55],	 antibacterial	 [56‐59],	 plant	 growth	
regulator	 [60],	 free	 radical	 scavenger	 [61],	 trypsin	 inhibitor	
[62],	 inhibitor	 of	 cartilage	 matrix	 degeneration	 [63],	 5‐HT6	
antagonist	 [64],	 anti‐inflammatory	 [65]	 and	 analgesic	 [66,67].	
Similarly,	 chalcones	 (α,β‐unsatured	 ketones)	 captivated	
significant	 attention	 in	 drug	 discovery	 chemistry.	 Chalcones	
(α,β‐unsatured	ketones)	have	gained	huge	significance	as	these	
compounds	 exhibit	 several	 biological	 activities,	 such	 as	
antimicrobial	 [68],	 antiviral	 [69],	 antioxidant	 [70],	 radical	
inhibitor	 [71],	 antitumor	 [72],	 carbonic	 anhydrase	 inhibitor	
[73],	 xanthine	 oxidase	 inhibitor	 [74],	 antibacterial	 [75],	 plant	
growth	regulator	[76],	free	radical	scavenger	[77],	anti‐inflam‐
matory	[78]	and	analgesic	[79].		

As	 a	 part	 of	 our	 on‐going	 research	 in	 systematic	 investi‐
gation	 of	 synthesizing	 some	 novel	 bioactive	 compounds	 in	
relation	to	 their	Mtb	H37Rv	 inhibitory	activity,	we	prepared	a	
series	 of	 some	novel	 1,3,5‐triazine‐chalcone	 hybrid	molecules	
(4a‐ii)	 [80].	 However,	 we	 have	 found	 that	 1,3,5‐triazine‐
chalcone	 hybrid	 molecules	 (4a‐ii)	 have	 the	 considerable	
potential	to	act	as	a	new	class	of	Mtb	H37Rv	inhibitors,	which	
can	be	obtained	with	the	efficient	methods	in	organic	synthesis	
(Scheme	1).	The	novelty	of	this	work	is	that	none	of	the	1,3,5‐
triazine‐chalcone	 hybrid	 molecules	 (4a‐ii)	 synthesized	 in	 the	
present	 study	 were	 earlier	 not	 reported	 to	 possess	 any	
inhibitory	activity	against	Mtb	H37Rv	strain.	
	
2.	Experimental	 	
	
2.1.	Instrumentation	

	
Melting	points	were	 taken	 in	open	capillary	 tubes	and	are	

therefore	 uncorrected.	 Purity	 of	 the	 compounds	was	 checked	
on	silica	gel	G	TLC	plates	of	2	mm	thickness	using	n‐hexane	and	
ethyl	 acetate	 as	 solvent	 system.	The	 visualization	 of	 spot	was	
carried	 out	 in	 an	 iodine	 chamber.	 The	 FT‐IR	 spectra	 were	
recorded	 on	Perkin‐Elmer	 spectrometer.	 The	 1H	NMR	 spectra	
were	scanned	on	a	Bruker	400	MHz.	spectrometer	in	DMSO‐d6	
using	 TMS	 as	 internal	 standard	 and	 chemical	 shifts	 are	
expressed	in	δ	ppm.	The	electronspray	ionisation	mass	spectra	

(ESI‐MS)	were	recorded	on	an	Agilent	6100	QQQ	mass	spectro‐
meter	 (positive	 ion	 mode).	 The	 UV‐Vis	 absorption	 spectra	 of	
the	 compounds	 were	 recorded	 on	 a	 Hitachi	 U‐1600	 spectro‐
photometer.		

	
2.2.	General	procedure	for	the	synthesis	of	1,3,5‐triazine‐
chalcone	hybrid	molecules	(4a‐ii)	
	

The	reaction	sequence	intended	for	the	preparation	of	title	
compounds	 (4a‐ii)	 is	 shown	 in	 Scheme	 1,	 and	 their	 physical	
properties	 are	 depicted	 in	 Table	 1.	 The	 chief	 intermediate	 in	
the	 present	 study	 1‐(4‐(4,6‐dichloro‐1,3,5‐triazin‐2‐ylamino)	
phenyl)ethanone	 (3)	 was	 prepared	 by	 reaction	 between	
cyanuric	 chloride	 i.e.	 2,4,6‐trichloro‐1,3,5‐triazine	 (1)	 and									
4‐aminoacetophenone	 (2)	 [10].	 Further,	 successive	 base	
catalyzed	 Claisen‐Schmidt	 condensation	 of	 the	 compound	 3	
with	 appropriate	 substituted	 aromatic/heteroaromatic	
aldehydes	 in	 the	 presence	 of	 100%	 potassium	 hydroxide	
solution	 in	 ethanol	 afforded	 a	 series	 of	 1‐(4‐(4,6‐dichloro‐1,3,	
5‐triazin‐2‐ylamino)phenyl)‐3‐(substituted)‐2‐propen‐1‐ones	
(4a‐ii)	 in	 good	 yield.	 All	 the	 newly	 synthesized	 compounds	
were	 characterized	 by	 CHN	 elemental	 analysis	 and	
spectroscopic	 methods	 such	 as	 FT‐IR,	 1H	 NMR,	 and	 LC	 mass	
spectral	analysis.	Eventually	all	the	spectra	of	the	new	products	
(4a‐ii)	are	in	keeping	with	the	predictable	structures.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐
(phenyl)‐2‐propen‐1‐one	(4a):	Colour:	Light	yellow	crystals.	FT‐
IR	 (KBr,	 vmax,	 cm‐1):	 3155	 (N−H),	 3031	 (C−H,	 aromatic),	 2884	
(C−H,	aliphatic),	1688	(C=O),	1645	(C=C,	aliphatic),	1513	(C=C,	
aromatic),	 689	 (C−Cl).	 1H	 NMR	 (400	MHz,	 DMSO‐d6,	 δ,	 ppm):	
7.13‐7.74	(m,	9H,	Ar‐H),	7.78	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	
8.01	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	9.74	(s,	1H,	NH).	ESI‐MS	
(m/z):	372	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(2‐
methylphenyl)‐2‐propen‐1‐one	 (4b):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3152	 (N−H),	 3022	 (C−H,	
aromatic),	 2881	 (C−H,	 aliphatic),	 1689	 (C=O),	 1623	 (C=C,	
aliphatic),	1501	(C=C,	aromatic),	688	(C−Cl).	1H	NMR	(400	MHz,	
DMSO‐d6,	 δ,	 ppm):	 2.32	 (s,	 3H,	 CH3),	 7.43‐8.04	 (m,	 8H,	 Ar‐H),	
7.78	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	8.01	(d,	J	=	15.2	Hz,	1H,	
HC=CH	(H‐β)),	9.74	(s,	1H,	NH).	ESI‐MS	(m/z):	386	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐
(3‐methylphenyl)‐2‐propen‐1‐one	 (4c):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3127	 (N−H),	 3027	 (C−H,	
aromatic),	 2777	 (C−H,	 aliphatic),	 1703	 (C=O),	 1603	 (C=C,	
aliphatic),	1450	(C=C,	aromatic),	688	(C−Cl).	1H	NMR	(400	MHz,	
DMSO‐d6,	 δ,	 ppm):	 2.41	 (s,	 3H,	 CH3),	 7.38‐8.05	 (m,	 8H,	 Ar‐H),	
7.73	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	8.04	(d,	J	=	15.2	Hz,	1H,	
HC=CH	(H‐β)),	9.69	(s,	1H,	NH).	ESI‐MS	(m/z):	386	[M+H]+.		



572	 Dwarampudi	et	al.	/	European	Journal	of	Chemistry	5	(4)	(2014)	570‐576	
	

	
Table	1.	Physical	characterization	and	Mycobacterium	tuberculosis	H37Rv	inhibitory	activity	data	of	1,3,5‐triaizne‐chalcone	hybrids	(4a‐ii)	and	standard	drugs.	
Compound	 R	 Molecular	

formula	
Molecular	
weight	(g)	

M.p.	
(oC)	

Yield		
(%)	a	

%	Elemental	analysis	of	C,	H,	N	b	 MIC	c	
(µg/mL)	Calculated Found		

C H N C H	 N	
4a	 Phenyl	 C18H12Cl2N4O	 371	 177	 81	 58.24	 3.26	 15.09	 58.21	 3.21	 15.05	 50	
4b	 2‐MeC6H4	 C19H14Cl2N4O	 385	 165	 79	 59.24	 3.66	 14.54	 59.22	 3.62	 14.52	 25	
4c	 3‐MeC6H4	 C19H14Cl2N4O	 385 181 88 59.24 3.66 14.54 59.25	 3.61	 14.53	 100
4d	 4‐MeC6H4	 C19H14Cl2N4O	 385	 144	 75	 59.24	 3.66	 14.54	 59.22	 3.64	 14.51	 50	
4e	 2‐OMeC6H4	 C19H14Cl2N4O2	 401	 152	 91	 56.87	 3.52	 13.96	 56.82	 3.51	 13.95	 6.25	
4f	 3‐OMeC6H4	 C19H14Cl2N4O2	 401 166 78 56.87 3.52 13.96 56.83	 3.51	 13.91	 25
4g	 4‐OMeC6H4	 C19H14Cl2N4O2	 401 171 74 56.87 3.52 13.96 56.84	 3.56	 13.96	 50
4h	 3‐OHC6H4	 C18H12Cl2N4O2	 387 118 77 55.83 3.12 14.47 55.85	 3.11	 14.42	 50
4i	 4‐OHC6H4	 C18H12Cl2N4O2	 387 129 88 55.83 3.12 14.47 55.83	 3.11	 14.45	 100
4j	 3,5‐diOHC6H3	 C18H12Cl2N4O3	 403 147 85 53.62 3.00 13.89 53.61	 3.02	 13.81	 50
4k	 4,5‐diOHC6H3	 C18H12Cl2N4O3	 403 154 84 53.62 3.00 13.89 53.61	 3.04	 13.82	 50
4l	 2‐Me,5‐OHC6H3	 C19H14Cl2N4O2	 401 169 85 56.87 3.52 13.96 56.86	 3.51	 13.93	 25
4m	 2‐NH2C6H4	 C18H13Cl2N5O	 386	 179	 83	 55.97	 3.39	 18.13	 55.95	 3.31	 18.11	 50	
4n	 3‐NH2C6H4	 C18H13Cl2N5O	 386	 122	 81	 55.97	 3.39	 18.13	 55.94	 3.32	 18.12	 100	
4o	 4‐NH2C6H4	 C18H13Cl2N5O	 386	 139	 74	 55.97	 3.39	 18.13	 55.93	 3.35	 18.14	 100	
4p	 2‐NO2C6H4	 C18H11Cl2N5O3	 416 111 84 51.94 2.66 16.83 51.95	 2.62	 16.82	 6.25
4q	 3‐NO2C6H4	 C18H11Cl2N5O3	 416 177 87 51.94 2.66 16.83 51.92	 2.65	 16.85	 25
4r	 4‐NO2C6H4	 C18H11Cl2N5O3	 416 174 74 51.94 2.66 16.83 51.93	 2.62	 16.81	 50
4s	 2‐ClC6H4	 C18H11Cl3N4O	 405 168 95 53.29 2.73 13.81 53.21	 2.71	 13.82	 12.5
4t	 3‐ClC6H4	 C18H11Cl3N4O	 405 151 77 53.29 2.73 13.81 53.22	 2.74	 13.81	 100
4u	 4‐ClC6H4	 C18H11Cl3N4O	 405 146 81 53.29 2.73 13.81 53.23	 2.71	 13.84	 25
4v	 2,4‐diClC6H3	 C18H10Cl4N4O	 440 194 92 49.12 2.29 12.73 49.11	 2.25	 12.71	 50
4w	 2‐FC6H4	 C18H11Cl2FN4O	 389	 112	 97	 55.55	 2.85	 14.39	 55.53	 2.82	 14.35	 50	
4x	 3‐FC6H4	 C18H11Cl2FN4O	 389	 150	 92	 55.55	 2.85	 14.39	 55.52	 2.84	 14.35	 50	
4y	 4‐FC6H4	 C18H11Cl2FN4O	 389	 130	 88	 55.55	 2.85	 14.39	 55.51	 2.81	 14.32	 25	
4z	 2,4‐diFC6H3	 C18H10Cl2F2N4O	 407 110 84 53.09 2.48 13.76 53.01	 2.42	 13.72	 3.125
4aa	 Furan‐2yl		 C16H10Cl2N4O2	 361 138 93 53.21 2.79 15.51 53.22	 2.75	 15.50	 25
4bb	 Thiophen‐3‐yl	 C16H10Cl2N4OS	 377 119 82 50.94 2.67 14.85 50.97	 2.65	 14.82	 6.25
4cc	 Pyrrol‐2yl	 C16H11Cl2N5O	 360 122 85 66.25 3.42 11.89 66.22	 3.41	 11.86	 25
4dd	 Pyridin‐2‐yl	 C17H11Cl2N5O	 372 138 77 54.86 2.98 18.82 54.82	 2.96	 18.88	 25
4ee	 Pyridin‐3‐yl	 C17H11Cl2N5O	 372 165 75 54.86 2.98 18.82 54.81	 2.95	 18.89	 100
4ff	 Pyridin‐4‐yl	 C17H11Cl2N5O	 372 201 83 54.86 2.98 18.82 54.85	 2.92	 18.81	 50
4gg	 Naphthalen‐2‐yl	 C22H14Cl2N4O	 421	 119	 87	 62.72	 3.35	 13.30	 62.71	 3.32	 13.32	 100	
4hh	 Naphthalen‐3‐yl	 C22H14Cl2N4O	 421	 147	 78	 62.72	 3.35	 13.30	 62.72	 3.31	 13.33	 100	
4ii	 Anthracen‐9‐yl	 C26H16Cl2N4O	 471 199 87 66.25 3.42 11.89 66.22	 3.40	 11.85	 100
Ethambutol	 3.125
Pyrazinamide	 3.125
Streptomycin		 6.25
a	Crystallization	solvent	is	ethanol.	
b	Elemental	analysis	of	C,	H,	and	N	were	within	±0.4%	of	theoretical	value.	
c	Mycobacterium	tuberculosis	H37Rv.	

	
	
(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(4‐

methylphenyl)‐2‐propen‐1‐one	 (4d):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3122	 (N−H),	 3015	 (C−H,	
aromatic),	 2762	 (C−H,	 aliphatic),	 1705	 (C=O),	 1601	 (C=C,	
aliphatic),	1440	(C=C,	aromatic),	685	(C−Cl).	1H	NMR	(400	MHz,	
DMSO‐d6,	 δ,	 ppm):	 2.39	 (s,	 3H,	 CH3),	 7.31‐7.66	 (m,	 8H,	 Ar‐H),	
7.73	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	8.02	(d,	J	=	15.2	Hz,	1H,	
HC=CH	(H‐β)),	9.62	(s,	1H,	NH).	ESI‐MS	(m/z):	386	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(2‐
methoxyphenyl)‐2‐propen‐1‐one	 (4e):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3124	 (N−H),	 3027	 (C−H,	
aromatic),	 2975	 (C−H,	 aliphatic),	 1700	 (C=O),	 1603	 (C=C,	
aliphatic),	 1417	 (C=C,	 aromatic),	 713	 (C−Cl),	 1171	 (C−O−C),	
1054	(C−O).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	3.86	(s,	3H,	
OCH3),	7.20‐8.05	(m,	8H,	Ar‐H),	7.48	(d,	J	=	15.2	Hz,	1H,	HC=CH	
(H‐α)),	8.05	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	9.66	(s,	1H,	NH).	
ESI‐MS	(m/z):	402	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(3‐
methoxyphenyl)‐2‐propen‐1‐one	 (4f):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3124	 (N−H),	 3027	 (C−H,	
aromatic),	 2977	 (C−H,	 aliphatic),	 1700	 (C=O),	 1605	 (C=C,	
aliphatic),	 1457	 (C=C,	 aromatic),	 687	 (C−Cl),	 1171	 (C−O−C),	
1054	(C−O).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	3.88	(s,	3H,	
OCH3),	7.12‐8.21	(m,	8H,	Ar‐H),	7.71	(d,	J	=	15.2	Hz,	1H,	HC=CH	
(H‐α)),	8.06	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	9.65	(s,	1H,	NH).	
ESI‐MS	(m/z):	402	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(4‐
methoxyphenyl)‐2‐propen‐1‐one	 (4g):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3122	 (N−H),	 3021	 (C−H,	
aromatic),	 2970	 (C−H,	 aliphatic),	 1690	 (C=O),	 1602	 (C=C,	

aliphatic),	 1455	 (C=C,	 aromatic),	 677	 (C−Cl),	 1170	 (C−O−C),	
1055	(C−O).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	3.86	(s,	3H,	
OCH3),	7.12‐7.92	(m,	8H,	Ar‐H),	7.71	(d,	J	=	15.2	Hz,	1H,	HC=CH	
(H‐α)),	8.05	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	9.75	(s,	1H,	NH).	
ESI‐MS	(m/z):	402	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(3‐
hydroxyphenyl)‐2‐propen‐1‐one	 (4h):	 Colour:	 Light	 yellow	
crystals.	FT‐IR	(KBr,	vmax,	cm‐1):	3445	(O−H),	3124	(N−H),	3015	
(C−H,	aromatic),	2984	(C−H,	aliphatic),	1689	(C=O),	1606	(C=C,	
aliphatic),	 1415	 (C=C,	 aromatic),	 676	 (C−Cl),	 1054	 (C−O).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.36‐8.01	 (m,	 8H,	 Ar‐H),	
7.67	(d,	J	=	15.6	Hz,	1H,	HC=CH	(H‐α)),	8.18	(d,	J	=	15.6	Hz,	1H,	
HC=CH	 (H‐β)),	 9.85	 (s,	 1H,	 NH),	 12.32	 (s,	 1H,	 OH).	 ESI‐MS	
(m/z):	388	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(4‐
hydroxyphenyl)‐2‐propen‐1‐one	 (4i):	 Colour:	 Light	 yellow	
crystals.	FT‐IR	(KBr,	vmax,	cm‐1):	3444	(O−H),	3124	(N−H),	3019	
(C−H,	aromatic),	2982	(C−H,	aliphatic),	1684	(C=O),	1602	(C=C,	
aliphatic),	 1412	 (C=C,	 aromatic),	 671	 (C−Cl),	 1055	 (C−O).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.16‐7.62	 (m,	 8H,	 Ar‐H),	
7.68	(d,	J	=	15.6	Hz,	1H,	HC=CH	(H‐α)),	8.14	(d,	J	=	15.6	Hz,	1H,	
HC=CH	 (H‐β)),	 9.82	 (s,	 1H,	 NH),	 12.31	 (s,	 1H,	 OH).	 ESI‐MS	
(m/z):	388	[M+H]+.	

(E)‐1‐(4‐(4,6‐dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(3,	
5‐dihydroxyphenyl)‐2‐propen‐1‐one	 (4j):	 Colour:	 Light	 yellow	
crystals.	FT‐IR	(KBr,	vmax,	cm‐1):	3440	(O−H),	3122	(N−H),	3027	
(C−H,	aromatic),	2890	(C−H,	aliphatic),	1700	(C=O),	1605	(C=C,	
aliphatic),	 1511	 (C=C,	 aromatic),	 688	 (C−Cl),	 1054	 (C−O).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.21‐8.02	 (m,	 7H,	 Ar‐H),	
7.79	(d,	J	=	15.3	Hz,	1H,	HC=CH	(H‐α)),	8.03	(d,	J	=	15.3	Hz,	1H,	



Dwarampudi	et	al.	/	European	Journal	of	Chemistry	5	(4)	(2014)	570‐576	 573	
 

HC=CH	 (H‐β)),	 9.89	 (s,	 1H,	 NH),	 11.52	 (s,	 2H,	 OH).	 ESI‐MS	
(m/z):	404	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(4,5	
‐dihydroxyphenyl)‐2‐propen‐1‐one	 (4k):	 Colour:	 Light	 yellow	
crystals.	FT‐IR	(KBr,	vmax,	cm‐1):	3395	(O−H),	3127	(N−H),	3017	
(C−H,	aromatic),	2989	(C−H,	aliphatic),	1686	(C=O),	1615	(C=C,	
aliphatic),	 1545	 (C=C,	 aromatic),	 689	 (C−Cl),	 1054	 (C−O).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.55‐8.03	 (m,	 7H,	 Ar‐H),	
7.83	(d,	J	=	15.3	Hz,	1H,	HC=CH	(H‐α)),	8.08	(d,	J	=	15.3	Hz,	1H,	
HC=CH	(H‐β)),	9.58	(s,	1H,	OH),	9.87	(s,	1H,	NH),	10.57	(s,	1H,	
OH).	ESI‐MS	(m/z):	404	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(2‐
methyl‐5‐hydroxyphenyl)‐2‐propen‐1‐one	 (4l):	 Colour:	 Light	
yellow	 crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3440	 (O−H),	 3122	
(N−H),	 3021	 (C−H,	 aromatic),	 2975	 (C−H,	 aliphatic),	 1690	
(C=O),	1641	(C=C,	aliphatic),	1486	(C=C,	aromatic),	678	(C−Cl),	
1054	(C−O).		1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	2.47	(s,	3H,	
CH3),	7.62‐8.01	(m,	7H,	Ar‐H),	7.81	(d,	 J	=	15.3	Hz,	1H,	HC=CH	
(H‐α)),	8.08	(d,	J	=	15.3	Hz,	1H,	HC=CH	(H‐β)),	9.01	(s,	1H,	NH),	
10.52	(s,	1H,	OH).	ESI‐MS	(m/z):	402	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(2‐
aminophenyl)‐2‐propen‐1‐one	 (4m):	 Colour:	 Light	 yellow	
crystals.	FT‐IR	(KBr,	vmax,	cm‐1):	3367	(NH2),	3117	(N−H),	2978	
(C−H,	aromatic),	2763	(C−H,	aliphatic),	1693	(C=O),	1597	(C=C,	
aliphatic),	 1413	 (C=C,	 aromatic),	 688	 (C−Cl),	 1296	 (C−N).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.74‐8.11	 (m,	 8H,	 Ar‐H),	
7.58	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	8.06	(d,	J	=	15.2	Hz,	1H,	
HC=CH	(H‐β)),	9.65	(s,	1H,	NH),	10.51	 (s,	2H,	Ar‐NH2).	ESI‐MS	
(m/z):	387	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(3‐
aminophenyl)‐2‐propen‐1‐one	 (4n):	 Colour:	 Light	 yellow	
crystals.	FT‐IR	(KBr,	vmax,	cm‐1):	3367	(NH2),	3117	(N−H),	2978	
(C−H,	aromatic),	2763	(C−H,	aliphatic),	1693	(C=O),	1597	(C=C,	
aliphatic),	 1413	 (C=C,	 aromatic),	 688	 (C−Cl)	 ,	 1290	 (C−N).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.72	 (d,	 J	 =	 15.2	 Hz,	 1H,	
HC=CH	(H‐α)),	7.74‐8.11	(m,	8H,	Ar‐H),	8.01	(d,	J	=	15.2	Hz,	1H,	
HC=CH	(H‐β)),	9.67	(s,	1H,	NH),	10.54	 (s,	2H,	Ar‐NH2).	ESI‐MS	
(m/z):	387	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(4‐
aminophenyl)‐2‐propen‐1‐one	 (4o):	 Colour:	 Light	 yellow	
crystals.	FT‐IR	(KBr,	vmax,	cm‐1):	3362	(NH2),	3115	(N−H),	2979	
(C−H,	aromatic),	2761	(C−H,	aliphatic),	1690	(C=O),	1590	(C=C,	
aliphatic),	 1410	 (C=C,	 aromatic),	 684	 (C−Cl),	 1290	 (C−N).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.71	 (d,	 J	 =	 15.2	 Hz,	 1H,	
HC=CH	(H‐α)),	7.77‐8.14	(m,	8H,	Ar‐H),	8.12	(d,	J	=	15.2	Hz,	1H,	
HC=CH	(H‐β)),	9.65	(s,	1H,	NH),	10.52	 (s,	2H,	Ar‐NH2).	ESI‐MS	
(m/z):	387	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(2‐
nitrophenyl)‐2‐propen‐1‐one	(4p):	Colour:	Light	yellow	crystals.	
FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3122	 (N−H),	 3024	 (C−H,	 aromatic),	
2776	(C−H,	aliphatic),	1700	(C=O),	1604	(C=C,	aliphatic),	1414	
(C=C,	aromatic),	688	(C−Cl),	1529	(N=O),	1291	(C−N).	1H	NMR	
(400	MHz,	DMSO‐d6,	δ,	ppm):	6.86‐8.18	(m,	8H,	Ar‐H),	8.05	(d,	J	
=	15.2	Hz,	1H,	HC=CH	 (H‐α)),	8.35	 (d,	 J	 =	15.2	Hz,	1H,	HC=CH	
(H‐β)),	9.72	(s,	1H,	NH).	ESI‐MS	(m/z):	417	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(3‐
nitrophenyl)‐2‐propen‐1‐one	(4q):	Colour:	Light	yellow	crystals.	
FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3115	 (N−H),	 3026	 (C−H,	 aromatic),	
2775	(C−H,	aliphatic),	1700	(C=O),	1599	(C=C,	aliphatic),	1412	
(C=C,	aromatic),	688	(C−Cl),	1522	(N=O),	1290	(C−N).	1H	NMR	
(400	MHz,	DMSO‐d6,	δ,	ppm):	7.55‐8.39	(m,	8H,	Ar‐H),	7.86	(d,	J	
=	15.2	Hz,	1H,	HC=CH	 (H‐α)),	8.06	 (d,	 J	 =	15.2	Hz,	1H,	HC=CH	
(H‐β)),	9.73	(s,	1H,	NH).	ESI‐MS	(m/z):	417	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(4‐
nitrophenyl)‐2‐propen‐1‐one	(4r):	Colour:	Light	yellow	crystals.	
FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3205	 (N−H),	 3016	 (C−H,	 aromatic),	
2895	(C−H,	aliphatic),	1710	(C=O),	1589	(C=C,	aliphatic),	1442	
(C=C,	aromatic),	680	(C−Cl),	1520	(N=O),	1287	(C−N).	1H	NMR	
(400	MHz,	DMSO‐d6,	δ,	ppm):	7.54‐8.29	(m,	8H,	Ar‐H),	7.83	(d,	J	
=	15.2	Hz,	1H,	HC=CH	 (H‐α)),	8.07	 (d,	 J	 =	15.2	Hz,	1H,	HC=CH	
(H‐β)),	9.23	(s,	1H,	NH).	ESI‐MS	(m/z):	417	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(2‐
chlorophenyl)‐2‐propen‐1‐one	 (4s):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3127	 (N−H),	 3027	 (C−H,	
aromatic),	 2893	 (C−H,	 aliphatic),	 1689	 (C=O),	 1597	 (C=C,	
aliphatic),	 1450	 (C=C,	 aromatic),	 688	 (C−Cl),	 786	 (C−Cl).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.60	 (d,	 J	 =	 15.2	 Hz,	 1H,	
HC=CH	(H‐α)),	7.62‐8.24	(m,	8H,	Ar‐H),	7.78	(d,	J	=	15.2	Hz,	1H,	
HC=CH	(H‐β)),	9.65	(s,	1H,	NH).	ESI‐MS	(m/z):	406	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(3‐
chlorophenyl)‐2‐propen‐1‐one	 (4t):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3121	 (N−H),	 3025	 (C−H,	
aromatic),	 2891	 (C−H,	 aliphatic),	 1686	 (C=O),	 1594	 (C=C,	
aliphatic),	1451	(C=C,	aromatic),	786	(C−Cl).	1H	NMR	(400	MHz,	
DMSO‐d6,	δ,	ppm):	7.45	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.62‐
7.74	(m,	8H,	Ar‐H),	7.79	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	9.65	
(s,	1H,	NH).	ESI‐MS	(m/z):	406	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(4‐
chlorophenyl)‐2‐propen‐1‐one	 (4u):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3126	 (N−H),	 3023	 (C−H,	
aromatic),	 2883	 (C−H,	 aliphatic),	 1690	 (C=O),	 1588	 (C=C,	
aliphatic),	 1442	 (C=C,	 aromatic),	 681	 (C−Cl),	 785	 (C−Cl).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.61	 (d,	 J	 =	 15.2	 Hz,	 1H,	
HC=CH	(H‐α)),	7.67‐7.82	(m,	8H,	Ar‐H),	7.87	(d,	J	=	15.2	Hz,	1H,	
HC=CH	(H‐β)),	9.63	(s,	1H,	NH).	ESI‐MS	(m/z):	406	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(2,	
4‐dichlorophenyl)‐2‐propen‐1‐one	 (4v):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3124	 (N−H),	 3018	 (C−H,	
aromatic),	 2891	 (C−H,	 aliphatic),	 1689	 (C=O),	 1641	 (C=C,	
aliphatic),	 1485	 (C=C,	 aromatic),	 691	 (C−Cl),	 786	 (C−Cl).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.65‐8.23	 (m,	 7H,	 Ar‐H),	
7.78	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	8.06	(d,	J	=	15.2	Hz,	1H,	
HC=CH	(H‐β)),	9.69	(s,	1H,	NH).	ESI‐MS	(m/z):	441	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(2‐
fluorophenyl)‐2‐propen‐1‐one	 (4w):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3117	 (N−H),	 3017	 (C−H,	
aromatic),	 2977	 (C−H,	 aliphatic),	 1693	 (C=O),	 1605	 (C=C,	
aliphatic),	 1415	 (C=C,	 aromatic),	 688	 (C−Cl),	 1116	 (C−F).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.36‐8.03	 (m,	 8H,	 Ar‐H),	
7.55	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.82	(d,	J	=	15.2	Hz,	1H,	
HC=CH	(H‐β)),	9.68	(s,	1H,	NH).	ESI‐MS	(m/z):	390	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(3‐
fluorophenyl)‐2‐propen‐1‐one	 (4x):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3112	 (N−H),	 3011	 (C−H,	
aromatic),	 2974	 (C−H,	 aliphatic),	 1690	 (C=O),	 1602	 (C=C,	
aliphatic),	 1412	 (C=C,	 aromatic),	 680	 (C−Cl),	 1011	 (C−F).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.16‐7.73	 (m,	 8H,	 Ar‐H),	
7.75	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.81	(d,	J	=	15.2	Hz,	1H,	
HC=CH	(H‐β)),	9.78	(s,	1H,	NH).	ESI‐MS	(m/z):	390	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(4‐
fluorophenyl)‐2‐propen‐1‐one	 (4y):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3114	 (N−H),	 3212	 (C−H,	
aromatic),	 2975	 (C−H,	 aliphatic),	 1694	 (C=O),	 1602	 (C=C,	
aliphatic),	 1412	 (C=C,	 aromatic),	 1106	 (C−F),	 685	 (C−Cl).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.22‐7.63	 (m,	 8H,	 Ar‐H),	
7.65	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.82	(d,	J	=	15.2	Hz,	1H,	
HC=CH	(H‐β)),	9.77	(s,	1H,	NH).	ESI‐MS	(m/z):	390	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(2,	
4‐difluorophenyl)‐2‐propen‐1‐one	 (4z):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3122	 (N−H),	 3021	 (C−H,	
aromatic),	 2884	 (C−H,	 aliphatic),	 1693	 (C=O),	 1605	 (C=C,	
aliphatic),	 1415	 (C=C,	 aromatic),	 688	 (C−Cl),	 1114	 (C−F).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.39‐8.31	 (m,	 7H,	 Ar‐H),	
7.76	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	8.08	(d,	J	=	15.2	Hz,	1H,	
HC=CH	(H‐β)),	9.69	(s,	1H,	NH).	ESI‐MS	(m/z):	408	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐
(furan‐2‐yl)‐2‐propen‐1‐one	 (4aa):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3420	 (N−H),	 3062	 (C−H,	
aromatic),	 3030	 (C−H,	 aliphatic),	 1671(C=O),	 1591	 (C=C,	
aliphatic),	 1453	 (C=C,	 aromatic),	 696	 (C−Cl),	 1155	 (C−O−C),	
1053	(C−O).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	6.74	(s,	1H,	
Ar‐H),	6.21	(m,	1H,	Ar‐H),	7.16‐7.50	(m,	5H,	Ar‐H),	7.62	(d,	J	=	



574	 Dwarampudi	et	al.	/	European	Journal	of	Chemistry	5	(4)	(2014)	570‐576	
	
16	Hz,	1H,	HC=CH	(H‐α)),	8.06	(d,	J	=	16	Hz,	1H,	HC=CH	(H‐β)),	
9.73	(s,	1H,	NH).	ESI‐MS	(m/z):	362	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐
(thiophen‐3‐yl)‐2‐propen‐1‐one	 (4bb):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3430	 (N−H),	 3019	 (C−H,	
aromatic),	 2973	 (C−H,	 aliphatic),	 1689	 (C=O),	 1599	 (C=C,	
aliphatic),	1414	(C=C,	aromatic),	688	(C−Cl).	1H	NMR	(400	MHz,	
DMSO‐d6,	δ,	ppm):	6.68	(s,	1H,	Ar‐H),	6.91	(s,	1H,	Ar‐H),	7.12	(s,	
1H,	 Ar‐H),	 7.33‐7.58	 (m,	 4H,	 Ar‐H),	 7.76	 (d,	 J	 =	 15.2	 Hz,	 1H,	
HC=CH	(H‐α)),	8.02	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	9.68	(s,	
1H,	NH).	ESI‐MS	(m/z):	378	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐
(pyrrol‐2‐yl)‐2‐propen‐1‐one	 (4cc):	 Colour:	 Light	 yellow	
crystals.	FT‐IR	(KBr,	vmax,	cm‐1):	3144	(N−H),	3052	(N−H),	3017	
(C−H,	aromatic),	2973	(C−H,	aliphatic),	1695	(C=O),	1615	(C=C,	
aliphatic),	 1414	 (C=C,	 aromatic),	 678	 (C−Cl),	 1308	 (C−N).	 1H	
NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	6.46	(s,	1H,	Ar‐H),	7.44	(m,	
1H,	 Ar‐H),	 7.55‐7.61	 (m,	 5H,	 Ar‐H),	 7.76	 (d,	 J	 =	 15.2	 Hz,	 1H,	
HC=CH	(H‐α)),	8.03	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	9.64	(s,	
1H,	NH),	10.55	(s,	1H,	NH).	ESI‐MS	(m/z):	361	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐
(pyridin‐2‐yl)‐2‐propen‐1‐one	 (4dd):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3127	 (N−H),	 3019	 (C−H,	
aromatic),	 2931	 (C−H,	 aliphatic),	 1689	 (C=O),	 1604	 (C=C,	
aliphatic),	 1417	 (C=C,	 aromatic),	 688	 (C−Cl),	 1308	 (C−N).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 6.98	 (d,	 J	 =	 16	 Hz,	 1H,	
HC=CH	(H‐α)),	7.13‐7.69	(m,	8H,	Ar‐H),	7.78	(d,	J	=	16	Hz,	1H,	
HC=CH	(H‐β)),	9.60	(s,	1H,	NH).	ESI‐MS	(m/z):	373	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐
(pyridin‐3‐yl)‐2‐propen‐1‐one	 (4ee):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3122	 (N−H),	 3011	 (C−H,	
aromatic),	 2922	 (C−H,	 aliphatic),	 1679	 (C=O),	 1609	 (C=C,	
aliphatic),	 1422	 (C=C,	 aromatic),	 1308	 (C−N),	 681	 (C−Cl).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.22	 (d,	 J	 =	 16	 Hz,	 1H,	
HC=CH	(H‐α)),	7.23‐7.59	(m,	8H,	Ar‐H),	7.68	(d,	J	=	16	Hz,	1H,	
HC=CH	(H‐β)),	9.58	(s,	1H,	NH).	ESI‐MS	(m/z):	373	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐
(pyridin‐4‐yl)‐2‐propen‐1‐one	 (4ff):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3127	 (N−H),	 3019	 (C−H,	
aromatic),	 2931	 (C−H,	 aliphatic),	 1689	 (C=O),	 1604	 (C=C,	
aliphatic),	 1417	 (C=C,	 aromatic),	 688	 (C−Cl),	 1308	 (C−N).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 6.98	 (d,	 J	 =	 16	 Hz,	 1H,	
HC=CH	(H‐α)),	7.13‐7.69	(m,	8H,	Ar‐H),	7.78	(d,	J	=	16	Hz,	1H,	
HC=CH	(H‐β)),	9.60	(s,	1H,	NH).	ESI‐MS	(m/z):	373	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐
(naphthalen‐2‐yl)‐2‐propen‐1‐one	 (4gg):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3102	 (N−H),	 3015	 (C−H,	
aromatic),	 2926	 (C−H,	 aliphatic),	 1684	 (C=O),	 1602	 (C=C,	
aliphatic),	1416	(C=C,	aromatic),	682	(C−Cl).	1H	NMR	(400	MHz,	
DMSO‐d6,	 δ,	 ppm):	 7.62‐7.83	 (m,	 11H,	Ar‐H),	 7.87	 (d,	 J	 =	 15.2	
Hz,	1H,	HC=CH	(H‐α)),	8.16	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	
9.70	(s,	1H,	NH).	ESI‐MS	(m/z):	422	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐
(naphthalen‐3‐yl)‐2‐propen‐1‐one	 (4hh):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3115	 (N−H),	 3019	 (C−H,	
aromatic),	 2931	 (C−H,	 aliphatic),	 1689	 (C=O),	 1604	 (C=C,	
aliphatic),	1417	(C=C,	aromatic),	688	(C−Cl).	1H	NMR	(400	MHz,	
DMSO‐d6,	 δ,	 ppm):	 7.62‐8.33	 (m,	 11H,	Ar‐H),	 7.89	 (d,	 J	 =	 15.2	
Hz,	1H,	HC=CH	(H‐α)),	8.26	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	
9.71	(s,	1H,	NH).	ESI‐MS	(m/z):	422	[M+H]+.		

(E)‐1‐(4‐(4,6‐Dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐
(anthracen‐9‐yl)‐2‐propen‐1‐one	 (4ii):	 Colour:	 Light	 yellow	
crystals.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3127	 (N−H),	 3019	 (C−H,	
aromatic),	 2931	 (C−H,	 aliphatic),	 1689	 (C=O),	 1604	 (C=C,	
aliphatic),	1417	(C=C,	aromatic),	688	(C−Cl).	1H	NMR	(400	MHz,	
DMSO‐d6,	 δ,	 ppm):	 6.98‐7.41	 (m,	 13H,	Ar‐H),	 7.59	 (d,	 J	 =	 15.6	
Hz,	1H,	HC=CH	(H‐α)),	8.06	(d,	J	=	15.6	Hz,	1H,	HC=CH	(H‐β)),	
9.75	(s,	1H,	NH).	ESI‐MS	(m/z):	472	[M+H]+.		

	
	
	

2.3.	Mycobacterium	tuberculosis	H37Rv	inhibitory	activity	
	

The	Mycobacterium	tuberculosis	inhibitory	activity	of	1,3,5‐
triazine‐chalcone	hybrid	molecules	4a‐ii	were	assessed	against	
Mtb	H37Rv	strain	using	micro	plate	Alamar	Blue	assay	(MABA)	
[81].	 This	 methodology	 is	 non‐toxic,	 uses	 a	 thermally	 stable	
reagent	 and	 shows	 good	 correlation	 with	 proportional	 and	
BACTEC	radiometric	method.	Briefly,	200	µL	of	sterile	deionzed	
water	was	added	to	all	outer	perimeter	wells	of	sterile	96	wells	
plate	 to	 minimized	 evaporation	 of	 medium	 in	 the	 test	 wells	
during	 incubation.	 The	 96	wells	 plate	 received	 100	 µL	 of	 the	
Middle	brook	7H9	broth	and	serial	dilution	of	compounds	was	
made	 directly	 on	 plate.	 The	 final	 drug	 concentrations	 tested	
were	 100	 to	 0.2	 µg/mL.	 Plates	were	 covered	 and	 sealed	with	
parafilm	and	incubated	at	37	°C	for	five	days.	After	this	time,	25	
µL	of	freshly	prepared	1:1	mixture	of	Alamar	Blue	reagent	and	
10%	tween	80	was	added	to	the	plate	and	incubated	for	24	h.	A	
blue	color	 in	 the	well	was	 interpreted	as	no	bacterial	 growth,	
and	pink	color	was	scored	as	growth.	The	MIC	was	defined	as	
lowest	 drug	 concentration,	which	 prevented	 the	 color	 change	
from	blue	to	pink.	The	results	of	Mtb	H37Rv	inhibitory	activity	
studies	are	given	in	Table	1.	

	
3.	Results	and	discussion		
	
3.1.	Synthesis	
	

The	 IR	 spectrum	of	 all	 the	 compounds	4a‐ii	 exhibited	 the	
characteristic	 absorptions	 at	 various	 frequencies	 correspond‐
dingly	 at	 3310‐3110	 and	 1640‐1715	 cm‐1	 suggesting	 the	
presence	 of	 a	 secondary	 amine	 group	 and	 α,β‐unsaturated	
carbonyl	 group	 respectively.	 In	 the	 1H	 NMR	 spectra	 of	 1‐(4‐
(4,6‐dichloro‐1,3,5‐triazin‐2‐ylamino)	 phenyl)‐3‐(substituted)‐
2‐propen‐1‐ones	 (4a‐ii),	 a	 singlet	 integrating	 for	 one	 proton	
characteristic	of	 the	secondary	amine	NH	group	was	observed	
in	between	δ	9.2‐9.4	ppm	as	a	broad	signal.	As	seen	in	case	of	
compound	4a,	 the	 IR	 spectrum	 of	4a	 exhibited	 characteristic	
−C=C−	 (aliphatic)	 and	 −C=C−	 (aromatic)	 stretching	 bands	 at	
frequencies	 1645	 and	 1513	 cm‐1,	 respectively.	 The	 other	 IR	
absorptions	 at	 various	 frequencies	 correspondingly	 at	 3155	
and	 1688	 cm‐1	 suggesting	 the	 presence	 of	 a	 secondary	 amino	
group	and	α,β‐unsaturatedketone	group,	respectively.	The	400	
MHz	 1H	 NMR	 spectrum	 of	 the	 compound	 4a	 in	 DMSO‐d6	 as	
solvent	 with	 TMS	 as	 an	 internal	 standard	 exhibited	 charac‐
teristic	peaks	 of	Hα	 and	Hβ	protons	 of	α,β‐unsaturated	 ketone	
bridge	 appeared	 as	 two	 doublets,	 one	 doublet	 at	 δ	 7.78	 ppm	
(Hα,	J	=	15.2	Hz)	and	the	other	one	at	δ	8.01	ppm	(Hβ,	J	=	15.2	
Hz).	 The	 large	 J	 value	 15.2	 Hz	 of	 both	 the	 protons	 clearly	
reveals	the	trans	geometry	at	the	double	bond.	The	distinguish‐
hing	peak	of	NH	proton	appears	as	one	singlet	δ	9.74	ppm.	The	
ESI	mass	spectrum	(positive	ion	mode)	of	4a	revealed	a	(M+H)+	
ion	 at	m/z	 372.	 Based	 on	 the	 above	 spectral	 information	 the	
structure	of	 the	compound	4a	was	confirmed	as	(Z)‐1‐(4‐(4,6‐
dichloro‐1,3,5‐triazin‐2‐ylamino)phenyl)‐3‐(phenyl)‐2‐propen‐
1‐one	[82‐84].	
	
3.2.	Mycobacterium	tuberculosis	H37RV	inhibitory	activity	
	

The	results	of	in	vitro	Mycobacterium	tuberculosis	(H37Rv)	
inhibitory	 activity	 of	 the	 synthesized	 1,3,5‐triazine‐chalcone	
hybrid	 molecules	 (4a‐ii)	 is	 illustrated	 in	 (Table	 1).	 The	
antitubercular	 activity	 screening	 data	 revealed	 that	 the	
compound	 4z	 demonstrated	 comparatively	 the	 most	 potent	
inhibitory	activity,	with	MIC	value	3.125	µg/mL.	It	is	interesting	
to	 note	 that	 the	 compounds	 4e,	 4p	 and	 4bb	 also	 showed	
appreciable	 inhibitory	 activity	 with	 MIC	 value	 6.25	 µg/mL.	
Compound	4s	was	also	showed	satisfactory	 inhibitory	activity	
with	MIC	value	12.5	µg/mL.	The	other	compounds	such	as	4b,	
4f,	4l,	4q,	4u,	4y,	4aa,	4cc	and	4dd	showed	moderate	 level	of	
activity	with	MIC	25	µg/mL.		



Dwarampudi	et	al.	/	European	Journal	of	Chemistry	5	(4)	(2014)	570‐576	 575	
 

The	compounds	4a,	4d,	4g,	4h,	4j,	4k,	4m,	4r,	4v,	4w,	4x	
and	4ff	 exhibited	comparatively	 reasonable	 inhibitory	activity	
with	MIC	value	50	µg/mL.	Correspondingly,	the	compounds	4c,	
4i,	4n,	4o,	4t,	4ee,	4gg,	4hh	 and	4ii	 exhibited	 comparatively	
poor	 inhibitory	 activity	 with	 MIC	 value	 100	 µg/mL	 in	
comparison	with	 the	 standard	 drugs	 (Ethambutol,	MIC:	 3.125	
µg/mL;	 Pyrazinamide,	 MIC:	 3.125	 µg/mL	 and	 Streptomycin,	
MIC:	6.25	µg/mL).		

A	 direct	 revision	 into	 the	 Structure‐Activity	 Relationship	
(SAR)	 of	 these	 compounds	 clearly	 exhibited	 the	 intrinsic	
property	 of	 Mycobacterium	 tuberculosis	 (H37Rv)	 inhibitory	
activity	 associated	with	 the	basic	 skeleton	 consisting	 of	1,3,5‐
triazine	 and	 α,β‐unsaturatedketone	 moieties	 [85]	 with	 MIC	
values	 range	 100‐3.125	 µg/mL.	 It	 is	 noteworthy	 that	 the	
observed	 inhibitory	 activity	 of	 1,3,5‐triazine‐chalcone	 hybrid	
molecules	 4a‐ii	 against	 Mycobacterium	 tuberculosis	 (H37Rv)	
revealed	 the	 importance	 of	 the	 type	 of	 substituted	 aromatic/	
heteroaromatic	aldehyde	 from	which	 the	corresponding	1,3,5‐
triazine‐chalcone	hybrid	molecules	4a‐ii	were	obtained,	which	
in	 some	 cases	 was	 enhanced	 by	 the	 influence	 of	 some	
substituents	 and	 decreased	 by	 some	 other	 substituents.	 The	
aromatic/heteroaromatic	 aldehydes	 derived	 chalcone	 deriva‐
tives	 of	 1,3,5‐triazine,	 as	 seen	 in	 the	 case	 of	 compounds	
followed	 its	 activity	 order	 as	 4bb	 (Thiophen‐3‐yl,	 MIC:	 6.25	
µg/mL)	 >	 4aa	 (Furan‐2yl,	 MIC:	 25	 µg/mL),	 4cc	 (Pyrrol‐2yl,	
MIC:	 25	 µg/mL),	 4dd	 (Pyridin‐2‐yl,	 MIC:	 25	 µg/mL)	 >	 4a	
(Phenyl,	MIC:	 50	µg/mL),	4ff	 (Pyridin‐4‐yl,	MIC:	 50	µg/mL)	>	
4ee	 (Pyridin‐3‐yl,	 MIC:	 100	 µg/mL),	 4gg	 (Naphthalen‐2‐yl,	
MIC:	100	µg/mL),	4hh	(Naphthalen‐3‐yl,	MIC:	100	µg/mL),	4ii	
(Anthracen‐9‐yl,	 MIC:	 100	 µg/mL),	 respectively.	 The	
compounds	4z	(2,4‐diFC6H3,	MIC:	3.125	µg/mL)	>	4s	(2‐ClC6H4,	
MIC:	12.5	µg/mL)	>	4u	(4‐ClC6H4,	MIC:	25	µg/mL),	4y	(4‐FC6H4,	
MIC:	 25	 µg/mL)	 >	 4v	 (2,4‐diClC6H3,	 MIC:	 50	 µg/mL),	 4w	 (2‐
FC6H4,	MIC:	50	µg/mL),	4x	 (3‐FC6H4,	MIC:	50	µg/mL)	>	4t	 (3‐
ClC6H4,	 MIC:	 100	 µg/mL)	 displayed	 better	 inhibitory	 potency	
indicating	 the	 significance	 of	 halogen	 substituents	 on	 the	
phenyl	ring	of	1,3,5‐traizine‐chalcone	motif.	 It	 is	also	reported	
that	 the	 compounds	 substituted	 with	 electron	 releasing	 or	
activating	groups	was	found	to	be	biologically	relevant	and	the	
activity	order	was	4e	 (2‐OMeC6H4,	MIC:	6.25	µg/mL)	>	4b	 (2‐
MeC6H4,	MIC:	 25	 µg/mL),	4f	 (3‐OMeC6H4,	MIC:	 25	 µg/mL),	4l	
(2‐Me,5‐OHC6H3,	 MIC:	 25	 µg/mL)	 >	 4d	 (4‐MeC6H4,	 MIC:	 50	
µg/mL),	4g	 (4‐OMeC6H4,	MIC:	50	µg/mL),	4h	 (3‐OHC6H4,	MIC:	
50	 µg/mL),	 4j	 (3,5‐diOHC6H3,	 MIC:	 50	 µg/mL),	 4k	 (4,5‐
diOHC6H3,	MIC:	50	µg/mL),	4m	(2‐NH2C6H4,	MIC:	50	µg/mL)	>	
4c	 (3‐MeC6H4,	 MIC:	 100	 µg/mL),	 4i	 (4‐OHC6H4,	 MIC:	 100	
µg/mL),	4n	(3‐NH2C6H4,	MIC:	100	µg/mL),	4o	(4‐NH2C6H4,	MIC:	
100	 µg/mL),	 respectively.	 The	 compounds	 substituted	 with	
electron	withdrawing	or	deactivating	nitro	group	was	found	to	
be	 biologically	 relevant	 and	 the	 activity	 order	 was,	 4p	 (2‐
NO2C6H4,	MIC:	6.25	µg/mL)	>	4q	(3‐NO2C6H4,	MIC:	25	µg/mL)	>	
4r	(4‐NO2C6H4,	MIC:	50	µg/mL),	respectively.	It	is	reported	that	
considerable	activity	was	observed	when	 the	hydroxyl	groups	
are	substituted	at	different	positions	on	the	phenyl	ring	as	seen	
in	the	case	of	compounds	4l	(2‐Me,5‐OHC6H3,	MIC:	25	µg/mL)	>	
4h	 (3‐OHC6H4,	 MIC:	 50	 µg/mL),	 4j	 (3,5‐diOHC6H3,	 MIC:	 50	
µg/mL),	 4k	 (4,5‐diOHC6H3,	 MIC:	 50	 µg/mL)	 >	 4i	 (4‐OHC6H4,	
MIC:	100	µg/mL),	respectively.	
	
4.	Conclusion	
	

A	series	of	new	class	of	Mycobacterium	tuberculosis	H37Rv	
inhibitors	 is	 reported,	 the	 synthesis	 of	which	 is	 characterized	
by	conventional	methods.	During	this	study	we	have	identified	
a	 number	 of	 1,3,5‐triazine‐chalcone	 hybrid	 molecules	 (4a‐ii)	
empowered	with	significant	Mycobacterium	tuberculosis	H37Rv	
inhibitory	 properties.	 Structure	 activity	 relationship	 studies	
revealed	 that	 substitution	 at	 position	 3	 of	 α,β‐unsaturated	
ketone	 further	 substitution	 is	 important	 to	 modulate	 the	
activity.	Further	studies	determining	the	in	vivo	antitubercular	
activity	of	these	compounds	are	under	progress.		

Acknowledgements	
	

One	 of	 the	 authors	Mr.	 Dwarampudi	 Subbarayal	 Reddy	 is	
thankful	 to	 the	 Principal,	 Andhra	 University	 College	 of	
Pharmaceutical	 Sciences,	 Andhra	 University,	 Visakhapatnam,	
for	 providing	 necessary	 facilities	 in	 carrying	 out	 the	 research	
work.		
	
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