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European	Journal	of	Chemistry	5	(1)	(2014)	133‐137	

	

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.5.1.133‐137.923	

	
	

	

	

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

	 	 	

Microwave	assisted	synthesis	of	2‐amino‐6‐methoxy‐4H‐benzo[h]chromene	
derivatives	

Ahmed	Mohamed	El‐Agrody	a,b,*,	Al‐Anood	Mohamed	Al‐Dies	b	and	Ahmed	Mahmoud	Fouda	b	

a	Chemistry	Department,	Faculty	of	Science,	Al‐Azhar	University,	Nasr	City,	Cairo,	11884,	Egypt	
b	Chemistry	Department,	Faculty	of	Science,	King	Khalid	University,	Abha,	61413,	Saudi	Arabia	

*Corresponding	author	at:	Chemistry	Department,	Faculty	of	Science,	Al‐Azhar	University,	Nasr	City,	Cairo,	11884,	Egypt.		
Tel.:	+2.02.22629358.	Fax:	+2.02.22629358.	E‐mail	address:	elagrody_am@yahoo.com		(A.M.	El‐Agrody).	

	
	

	 	

	 	 	
ARTICLE	INFORMATION	 	 ABSTRACT	

	
DOI:	10.5155/eurjchem.5.1.133‐137.923	

Received:	10	September	2013	
Received	in	revised	form:	13	November	2013	
Accepted:	13	November	2013	
Online:	31	March	2014	

KEYWORDS	

	 A	 convenient	 and	 efficient	 method	 using	 microwave	 assisted	 synthesis	 of	 4H‐
benzo[h]chromenes	(7	and	8),	by	the	reaction	of	4‐methoxy‐1‐naphthol	(1)	with	a	mixture	of
aromatic	 aldehydes	 (2)	 and	 malononitrile	 (3)	 or	 ethyl	 cyanoacetate	 (5)	 and	 also,	 by	 the
reaction	 of	 4‐methoxy‐1‐naphthol	 (1)	 with	 α‐cyanocinnamonitriles	 (4)	 or	 ethyl	 α‐
cyanocinnamates	(6)	 in	ethanolic	piperidine	solution	was	examined.	Structures	of	 the	newly
synthesized	compounds	were	established	on	the	basis	of	spectral	data,	IR,	1H	NMR,	13C	NMR,
13C	NMR‐DEPT	and	MS	data.	

Benzochromenes		
Pyran	derivatives	
Microwave	synthesis	
4‐Methoxy‐1‐naphthol		
α‐Cyanocinnamonitriles	
Ethyl	α‐cyanocinnamates	

	
1.	Introduction	
	

2‐Aminochromenes	 are	 important	 class	 of	 heterocyclic	
compounds	 having	 important	 biological	 activities.	 During	 the	
last	 decade,	 such	 compounds	 have	 shown	 interesting	
pharmacological	 properties	 including,	 antimicrobial	 [1‐5],	
antileishmanial	 [6‐9],	 anticancer	 [10,11],	 antioxidant	 [12‐15],	
hypertensive	 [16],	 antiproliferative	 [17],	 antitumor	 [18‐27]	
effects	 and	 activities,	 as	 well	 as	 treatment	 of	 Alzheimer’s	
disease	[28]	and	Schizophrenia	disorder	[29].	Fused	chromene	
ring	 systems	 have	 blood	 platelet	 antiaggregating	 [30],	
antihistaminic	 [31]	 and	 analgesic	 activities	 [32‐36].	 They	 also	
exhibit	hypolipidemic	activity	[37],	DNA	breaking	activities	and	
mutagenicity	[38].		

Recently,	 several	 methods	 for	 the	 synthesis	 of	 2‐
aminochromenes	 and	 2‐aminobenzochromenes	 have	 been	
described	[10,39,40].	Various	catalysts	such	as	piperidine	[41‐
44],	 morpholine	 [45],	 CTACl	 (Cetyltrimethylammonium	
chloride)	 [46],	 or	 CTABr	 (Cetyltrimethylammonium	 bromide)	
[47],	 o‐quinone	 methides	 (o‐QMs)	 [48,49]	 and	 alumina	 [50]	
have	been	used	 for	the	preparation	of	2‐aminochromenes	and	
2‐aminobenzochromenes.	 However,	 most	 of	 the	 reported	
methods	 require	 prolonged	 reaction	 time,	 stoichiometric	
reagents,	and	toxic	solvents	but	generate	only	moderate	yields	
of	the	product.	

Microwave	 heating	 has	 been	 known	 for	 accelerating	 the	
organic	reactions	[51‐53].	Cyclocondensation	reactions	 in	“dry	
media”	 leading	 to	 heterocyclic	 systems	 have	 been	 performed	
under	 microwave	 irradiation	 [54‐60].	 The	 reactions	 were	
carried	 out	 in	 a	 neat,	 solvent‐free	 state	 or	 in	 ethanol	 under	
microwave	irradiation	help	to	generate	products	not	attainable	
through	classical	heating	methods.	

In	 continuation	 of	 our	 program	 on	 the	 chemistry	 of	 4H‐
pyran	 derivatives	 [10,42,61‐73],	 it	 seemed	 interesting	 to	
synthesize	 new	 4H‐benzo[h]chromene	 derivatives	 by	 using	 a	
mixture	 of	 aromatic	 aldehydes/malononitrile	 or	 α‐cyano‐
cinnamonitriles	 and	 a	 mixture	 of	 aromatic	 aldehydes/ethyl	
cyanoacetate	or	ethyl	α‐cyanocinnamates	aiming	for	evaluation	
of	their	antitumor	activities	and	DNA	extractions.		
	
2.	Experimental		
	
2.1.	Instrumentation	
	

Melting	points	were	determined	with	a	Stuart	Scientific	Co.	
Ltd	apparatus.	IR	spectra	were	determined	as	KBr	pellets	on	a	
Jasco	 FT/IR	 460	 plus	 spectrophotometer.	 1H	 and	 13C	 NMR	
spectra	were	recorded	on	a	BRUKER	AV	500	MHz	spectrometer	
using	 tetramethylsilane	 (TMS)	 as	 an	 internal	 reference	 and	
results	are	expressed	as	δ	(ppm)	values.		



134	 El‐Agrody	et	al.	/	European	Journal	of	Chemistry	5	(1)	(2014)	133‐137	
	

	

	

Scheme	1	
	
	
13C	 NMR	 spectra	 were	 obtained	 using	 distortionless	

enhancement	 by	 polarization	 transfer	 (DEPT),	 with	 this	
technique,	 the	 signals	 of	 CH	 and	 CH3	 carbon	 atoms	 appears	
normal	 (up)	 and	 the	 signal	 of	 carbon	 atoms	 in	 CH2	
environments	 appears	 negative	 (down).	 The	 Microwave	
apparatus	 used	 is	 Milestone	 Sr1,	 Microsynth.	 The	 MS	 were	
measured	 on	 a	 Shimadzu	 GC/MS‐QP5050A	 spectrometer.	
Elemental	analyses	for	C,	H	and	N	were	performed	on	a	Perkin‐
Elmer	240	microanalyser.	
	
2.2.	General	procedure	for	the	preparation	of	4H‐benzo[h]	
chromene‐3‐carbonitrile	derivatives	(7a‐f)	
	

A	solution	of	4‐methoxy‐1‐naphthol	1	(0.01	mmol)	in	EtOH	
(30	mL)	and	piperidine	(0.5	mL)	was	treated	with	a	mixture	of	
aromatic	 aldehydes	2	 (0.01	mmol)	 and	malononitrile	3	 (0.01	
mmol)	or	α‐cyanocinnamonitriles	4	(0.01	mmol).	The	reaction	
mixture	 was	 heated	 under	 microwave	 irradiation	 conditions	
for	2	min	at	400	W	/	140	°C.	The	solid	product	which	formed	
was	 collected	 by	 filtration,	 washed	 with	 MeOH	 and	
recrystallized	 from	 ethanol.	 The	 physical	 and	 spectral	 data	 of	
compounds	7a‐f	are	as	follows	(Scheme	1):	

2‐Amino‐4‐(4‐fluorophenyl)‐6‐methoxy‐4H‐benzo[h]chrome	
ne‐3‐carbonitrile	 (7a):	 Color:	 Pale	 yellow	 crystals.	 Yield:	 89%.	
M.p.:	220‐221	οC	(M.p.:	218‐219	οC	[74]).	FT‐IR	(KBr,	υ,	cm	‐1):	
3457,	 3398,	 3284	 (NH2),	 3071,	 3003,	 2942,	 2870	 (CH	 str.),	
2193	 (CN).	 1H	NMR	(500	MHz,	DMSO‐d6,	 δ,	ppm):	3.80	 (s,	3H,	
CH3O),	4.89	(s,	1H,	H‐4),	7.14	(s,	2H,	NH2),	8.21‐6.51	(m,	9H,	Ar‐
H).	13C	NMR	(125	MHz,	DMSO‐d6,	δ,	ppm):	162.05	(2C),	151.19	
(6C),	141.74	 (10bC),	129.43	 (10aC),	127.25	 (9C),	 126.23	 (8C),	
124.40	(6aC),	123.64	(7C),	121.63	(10C),	120.60	(4aC),	117.59	
(CN),	103.29	(5C),	56.02	(3C),	55.98	(CH3O),	40.65	(4C),	160.38,	
136.82,	 129.36,	 115.49	 (Ar‐C).	 MS	 (EI,	 m/z	 (%)):	 346	 (M+,	
40.86),	 251	 (100).	 Anal.	 calcd.	 for	 C21H15FN2O2:	 C,	 72.82;	 H,	
4.37;	N,	8.09.	Found:	C,	72.80;	H,	4.34;	N,	8.06	%.	

2‐Amino‐4‐(4‐chlorophenyl)‐6‐methoxy‐4H‐benzo[h]chrome	
ne‐3‐carbonitrile	 (7b):	 Color:	 Colourless	 needles.	 Yield:	 91	%.	
M.p.:	218‐219	οC	(M.p.:	218‐219	οC	[75]).	FT‐IR	(KBr,	υ,	cm	‐1):	
3466,	 3330,	 3199	 (NH2),	 3080,	 3000,	 2962,	 2810	 (CH	 str.),	
2194	 (CN).	 1H	NMR	 (500	MHz,	DMSO‐d6,	 δ	 ppm):	 3.81	 (s,	 3H,	
CH3O),	4.89	 (s,	1H,	H‐4),	7.15	 (bs,	2H,	NH2,	 cancelled	by	D2O),	
8.21‐6.52	(m,	9H,	Ar‐H).	13C	NMR	(125	MHz,	DMSO‐d6,	δ,	ppm):	
160.41	(2C),	151.23	(6C),	144.47	(10bC),	131.48	(10aC),	127.30	
(9C),	 126.31	 (8C),	 123.62	 (6aC),	 121.65	 (7C),	 120.61	 (10C),	
120.48	 (4aC),	 117.27	 (CN),	 103.27	 (5C),	 55.72	 (CH3O),	 55.67	
(3C),	 40.74	 (4C),	 136.87,	 129.39,	 128.67,	 124.43	 (Ar‐C).	 13C	
NMR‐DEPT	(125	MHz,	DMSO‐d6,	δ,	ppm,	135о	CH,	CH3	(↑),	CH2	
(↓)):	 129.39	 (↑	 Ar‐CH),	 128.67	 (↑	 Ar‐CH),	 127.30	 (↑	 9CH),	
126.31	 (↑	 8CH),	 121.65	 (↑	 7CH),	 120.61	 (↑	 10CH),	 103.27	 (↑	
5CH),	55.72	(↑CH3O),	40.74	(↑	4CH).	13C	NMR‐DEPT	(125	MHz,	
DMSO‐d6,	δ,	ppm,	90о	CH	(↑)):	129.39	(↑	Ar‐CH),	128.67	(↑	Ar‐
CH),	127.30	(↑	9CH),	126.31	(↑	8CH),	121.65	(↑	7CH),	120.61	(↑	

10CH),	 103.27	 (↑	 5CH),	 40.74	 (↑	 4CH).	 13C	 NMR‐DEPT	 (125	
MHz,	DMSO‐d6,	δ,	ppm,	45о	CH,	CH2,	CH3	(↑)):	129.39	(↑	Ar‐CH),	
128.67	 (↑	 Ar‐CH),	 127.30	 (↑	 9CH),	 126.31	 (↑	 8CH),	 121.65	 (↑	
7CH),	120.61	(↑	10CH),	103.27	(↑	5CH),	55.72	(↑CH3O),	40.74	(↑	
4CH).	 	MS	(EI,	m/z	 (%)):	364	(M++2,	4.31),	362	(M+,	18.7),	75	
(100).	Anal.	 calcd.	 for	C21H15ClN2O2:	C,	 69.52;	H,	4.17;	N,	7.72.	
Found:	C,	69.80;	H,	4.22;	N,	7.79	%.		

2‐Amino‐4‐(4‐bromophenyl)‐6‐methoxy‐4H‐benzo[h]chrome	
ne‐3‐carbonitrile	 (7c):	 Color:	 Colourless	 crystals.	 Yield:	 88	%.	
M.p.:	230‐231	οC.	FT‐IR	(KBr,	υ,	cm	‐1):	3456,	3335,	3255	(NH2),	
3070,	 3008,	 2973,	 2875	 (CH	 str.),	 2191	 (CN).	 1H	 NMR	 (500	
MHz,	CDCl3,	δ,	ppm):	3.82	(s,	3H,	CH3O),	4.75	(bs,	2H,	NH2),	4.78	
(s,	1H,	H‐4),	8.20‐6.18	(m,	9H,	Ar‐H).	13C	NMR	(125	MHz,	CDCl3,	
δ,	 ppm):	 159.16	 (2C),	 152.44	 (6C),	 137.50	 (10bC),	 128.34	
(10aC),	 126.31	 (9C),	 125.49	 (8C),	 124.11	 (6aC),	 122.27	 (7C),	
121.35	 (10C),	 120.49	 (4aC),	 116.10	 (CN),	 102.74	 (5C),	 60.53	
(3C),	55.68	(CH3O),	41.52	(4C),	143.37,	131.98,	129.76,	119.76	
(Ar‐C).	MS	 (EI,	m/z	 (%)):	 408	 (M++2,	43.63),	 406	 (M+,	 44.27),	
250	 (100).	 Anal.	 calcd.	 for	 C21H15BrN2O2:	 C,	 61.93;	 H,	 3.71;	N,	
6.88.	Found:	C,	61.52;	H,	4.21;	N,	6.12	%.	

2‐Amino‐4‐(4‐methoxyphenyl)‐6‐methoxy‐4H‐benzo[h]chro	
mene‐3‐carbonitrile	(7d):	Color:	Colourless	needles.	Yield:	87%.	
M.p.:	180‐181	οC.	FT‐IR	(KBr,	υ,	cm	‐1):	3443,	3332,	3207	(NH2),	
3079,	 3029,	 2995,	 2947,	 2895,	 2839	 (CH	 str.),	 2193	 (CN).	 1H	
NMR	(500	MHz,	DMSO‐d6,	δ,	ppm):	3.81	(s,	3H,	OCH3),	3.72	(s,	
3H,	 CH3O),	 4.80	 (s,	 1H,	 H‐4),	 7.07	 (bs,	 2H,	 NH2,	 cancelled	 by	
D2O),	8.11‐6.52	(m,	9H,	Ar‐H).	13C	NMR	(125	MHz,	DMSO‐d6,	δ,	
ppm):	160.25	(2C),	151.10	(6C),	137.64	(10bC),	128.56	(10aC),	
128.30	 (9C),	 127.17	 (6aC),	 126.10	 (8C),	 124.33	 (7C),	 123.66	
(10C),	 121.61	 (4aC),	 118.09	 (CN),	 103.44	 (5C),	 56.43	 (3C),	
55.64	(CH3O),	54.96	(CH3O),	40.70	(4C),	158.12,	136.74,	128.77,	
114.00	 (Ar‐C).	MS	 (EI,	m/z	 (%)):	 358	 (M+,	 13.92),	 251	 (100).	
Anal.	calcd.	for	C22H18N2O3:	C,	73.73;	H,	5.06;	N,	7.82.	Found:	C,	
73.79;	H,	5.11;	N,	7.89	%.	

2‐Amino‐4‐(2,4‐dimethoxyphenyl)‐6‐methoxy‐4H‐benzo[h]	
chromene‐3‐carbonitrile	 (7e):	 Color:	 yellow	 needles.	 Yield:	
81%.	M.p.:	218‐219	οC.	FT‐IR	(KBr,	υ,	cm	‐1):	3481,	3436,	3332	
(NH2),	 3001,	 2936,	 2837	 (CH	 str.),	 2186	 (CN).	 1H	 NMR	 (500	
MHz,	DMSO‐d6,	δ,	ppm):	3.73	(s,	3H,	CH3O),	3.82	(s,	3H,	CH3O),	
3.86	 (s,	3H,	CH3O),	5.13	 (s,	 1H,	H‐4),	6.97	 (bs,	 2H,	NH2),	 8.19‐
6.47	 (m,	 8H,	 Ar‐H).	 13C	 NMR	 (125	 MHz,	 DMSO‐d6,	 δ,	 ppm):	
161.01	(2C),	151.01	(6C),	136.93	(10bC),	127.09	(10aC),	125.94	
(9C),	 125.57	 (6aC),	 124.18	 (8C),	 123.58	 (7C),	 121.53	 (10C),	
120.72	 (4aC),	 118.33	 (CN),	 105.37	 (5C),	 55.68	 (3C),	 55.50	
(CH3O),	55.19	(CH3O),	55.11(CH3O),	40.03	(4C),	159.40,	157.22,	
129.28,	 120.49,	 102.96,	 98.67	 (Ar‐C).	 MS	 (EI,	m/z	 (%)):	 388	
(M+,	30.38),	374	(100).	Anal.	calcd.	for	C23H20N2O4:	C,	71.12;	H,	
5.19;	N,	7.21.	Found:	C,	71.21;	H,	5.45;	N,	7.22	%.	

2‐Amino‐4‐(3,4‐dimethoxyphenyl)‐6‐methoxy‐4H‐benzo[h]	
chromene‐3‐carbonitrile	(7f):	Color:	Pale	yellow	crystals.	Yield:	
83%.	M.p.:	205‐206	οC.		

	



El‐Agrody	et	al.	/	European	Journal	of	Chemistry	5	(1)	(2014)	133‐137	 135	
 

	

Ar-CH=C
CN

CO2Et

a; Ar = 4-F C6H4
b; Ar = 4-Cl C6H4
c; Ar = 4-Br C6H4
d; Ar = 4-CH3O C6H4
f; Ar = 3,4-CH3O C6H3

OH

(1)

OMe

(6) / EtOH / pip.

ArCHO (2a-f) / CNCH2CO2Et (5) or

MW / 400 W / 2 min.

(8e)

O NH2

CO2Et

Ar

MeO

(8a-d,f)

e; Ar = 2,4-CH3O C6H3

O NH2

CO2Et

Ar

MeO

	
	

Scheme	2
	
	
FT‐IR	(KBr,	υ,	cm	‐1):	3386,	3331,	3215	(NH2),	3062,	3004,	

2970,	 2939,	 2903,	 2828	 (CH	 str.),	 2193	 (CN).	 1H	 NMR	 (500	
MHz,	DMSO‐d6,	δ,	ppm):	3.82	(s,	3H,	CH3O),	3.72	(s,	3H,	CH3O),	
3.71	 (s,	3H,	CH3O),	4.79	 (s,	 1H,	H‐4),	7.05	 (bs,	2H,	NH2),	 8.21‐
6.58	 (m,	 8H,	 Ar‐H).	 13C	 NMR	 (125	 MHz,	 DMSO‐d6,	 δ,	 ppm):	
161.08	(2C),	151.77	(6C),	138.71	(10bC),	127.88	(10aC),	126.82	
(9C),	 125.04	 (6aC),	 124.35	 (8C),	 122.33	 (7C),	 121.31	 (10C),	
120.27	 (4aC),	 118.73	 (CN),	 104.19	 (5C),	 56.85	 (3C),	 56.40	
(CH3O),	56.23	(CH3O),	56.15	(CH3O),	41.72	(4C),	149.43,	148.47,	
137.36,	 121.43,	 112.71,	 112.11	 (Ar‐C).	MS	 (EI,	m/z	 (%)):	 388	
[M+,	 21.23]	 with	 a	 base	 peak	 at	 64	 (100).	 Anal.	 calcd.	 for	
C23H20N2O4:	C,	71.12;	H,	5.19;	N,	7.21.	Found:	C,	71.19;	H,	5.32;	
N,	7.38	%.	
	
2.3.	General	procedure	for	the	preparation	of	ethyl	4H‐
benzo[h]chromene‐3‐carboxylate	derivatives	(8a‐d,f)	
	

A	solution	of	4‐methoxy‐1‐naphthol	1	(0.01	mmol)	in	EtOH	
(30	mL)	and	piperidine	(0.5	mL)	was	treated	with	a	mixture	of	
aromatic	 aldehydes	 2	 (0.01	 mmol)	 and	 ethyl	 cyanoacetate	 5	
(0.01	mmol)	 or	 ethyl	 α‐cyanocinnamates	6	 (0.01	mmol).	 The	
reaction	 mixture	 was	 heated	 under	 microwave	 irradiation	
conditions	 for	 2	 min	 at	 400	 W	 /	 140	 оC.	 The	 solid	 product	
which	 formed	was	 collected	 by	 filtration,	washed	with	MeOH	
and	 recrystallised	 from	 ethanol	 or	 ethanol/benzene.	 The	
physical	and	spectral	data	of	compounds	8a‐d,f	are	as	 follows	
(Scheme	2):	

Ethyl	 2‐amino‐4‐(4‐fluorophenyl)‐6‐methoxy‐4H‐benzo[h]	
chromene‐3‐carboxylate	(8a):	Color:	Pale	yellow	crystals.	Yield:	
75	%.	M.p.:	162‐163	οC	 (M.p.:	162‐163	οC	[76]).	FT‐IR	(KBr,	υ,	
cm	 ‐1):	 3408,	 3302	 (NH2),	 3065,	 3020,	 2978,	 2935,	 2896	 (CH	
str.)	1668	(CO).	1H	NMR	(500	MHz,	DMSO‐d6,	δ,	ppm):	1.19	(t,	J	
=	 7	Hz,	3H,	CH3CH2),	 3.88	 (s,	 3H,	CH3O),	4.10	 (q,	 J	 =	7	Hz,	2H,	
CH3CH2),	4.99	(s,	1H,	H‐4),	7.49	(bs,	2H,	NH2),	8.17‐6.34	(m,	9H,	
Ar‐H).	 13C	 NMR	 (125	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 169.42	 (CO),	
162.31	(2C),	151.97	(6C),	137.31	(10bC),	129.33	(10aC),	126.94	
(9C),	 125.70	 (6aC),	 125.05	 (8C),	 124.24	 (7C),	 122.11	 (10C),	
120.53	 (4aC),	 103.42	 (5C),	 78.87	 (3C),	 59.47	 (CH3CH2),	 55.59	
(CH3O),	 40.73	 (4C),	 14.37	 (CH3CH2),	 160.37,143.33,	 129.55,	
114.96	 (Ar‐C).	 	MS	 (EI,	m/z	 (%)):	 393	 (M+,	 81.4)	with	 a	 base	
peak	at	298	(100).	Anal.	calcd.	for	C23H20FNO4:	C,	70.22;	H,	5.12;	
N,	3.56.	Found:	C,	70.30;	H,	5.48;	N,	3.41%.	

Ethyl	 2‐amino‐4‐(4‐chlorophenyl)‐6‐methoxy‐4H‐benzo[h]	
chromene‐3‐carboxylate	 (8b):	 	 Color:	 Colorless	 crystals.	 Yield:	
79	%.	M.p.:	160‐161	οC	 (M.p.:	160‐161	οC	[75]).	FT‐IR	(KBr,	υ,	

cm	‐1):	3408,	3302	(NH2),	3406,	3330	(NH2),	3030,	3010,	2981,	
2938,	2899	 (CH	str.),	 1666	 (CO).	 1H	NMR	 (500	MHz,	CDCl3,	 δ,	
ppm):	1.13	(t,	 J	=	7.5	Hz,	3H,	CH3CH2),	3.78	(s,	3H,	CH3O),	4.02	
(q,	J	=	7.5	Hz,	2H,	CH3CH2),	4.91	(s,	1H,	H‐4),	6.30	(bs,	2H,	NH2,	
cancelled	by	D2O),	8.10‐6.27	(m,	9H,	Ar‐H).	13C	NMR	(125	MHz,	
CDCl3,	δ,	ppm):	168.08	 (CO),	161.09	 (2C),	151.18	 (6C),	146.58	
(10bC),	128.30	(10aC),	127.07	(9C),	125.93	(8C),	124.18	(6aC),	
121.62	 (7C),	 120.59	 (10C),	 120.36	 (4aC),	 103.79	 (5C),	 76.00	
(3C),	58.62	(CH3CH2),	55.72	(CH3O),	40.08	(4C),	14.30	(CH3CH2),	
136.90,	 130.53,	 129.13,	 128.14	 (Ar‐C).	 13C	 NMR‐DEPT	 (125	
MHz,	125	MHz,	CDCl3,	δ,	ppm,	135о	CH,	CH3	(↑),	CH2	(↓)):	129.13	
(↑	Ar‐CH),	 128.14	 ((↑	Ar‐CH),	127.07	 (↑	9CH),	 125.93	 (↑	8CH),	
121.62	 (↑	 7CH),	 (↑	 10CH),	 103.79	 (↑	 5CH),	 58.62	 (↓	 CH3CH2),	
55.72	(↑	CH3O),	40.08	(↑	4CH),	(↑	CH3CH2).	13C	NMR‐DEPT	(125	
MHz,	CDCl3,	δ,	ppm,	90о	CH	(↑)):	129.13	(↑	Ar‐CH),	128.14	(↑	Ar‐
CH),	127.07	(↑	9CH),	125.93	(↑	8CH),	121.62	(↑	7CH),	120.59	(↑	
10CH),	 103.79	 (↑	 5CH),	 40.08	 (↑	 4CH).	 13C	 NMR‐DEPT	 (125	
MHz,	 CDCl3,	 δ,	 ppm,	 45о	 CH,	 CH2,	 CH3	 (↑)):	 129.13	 (↑	 Ar‐CH),	
128.14	 (↑	 Ar‐CH),	 127.07	 (↑	 9CH),	 125.93	 (↑	 8CH),	 121.62	 (↑	
7CH),	120.59	(↑	10CH),	103.79	(↑	5CH),	58.62	(↓	CH3CH2),	55.72	
(↑	CH3O),	 40.08	 (↑	 4CH),	 14.30	 (↑	CH3CH2).	MS	 (EI,	m/z	 (%)):	
411	 (M++2,	 5.31),	 409	 (M+,	 19.38),	 75	 (100).	 Anal.	 calcd.	 for	
C23H20ClNO4:	C,	67.40;	H,	4.92;	N,	3.42.	Found:	C,	67.74;	H,	4.42;	
N,	3.49	%.	

Ethyl	 2‐amino‐4‐(4‐bromophenyl)‐6‐methoxy‐4H‐benzo[h]	
chromene‐3‐carboxylate	 (8c):	 Color:	 Colorless	 needles.	
Crystallization:	From	ethanol/benzene.	Yield:	79	%.	M.p.:	165‐
166	 οC.	 FT‐IR	 (KBr,	 υ,	 cm	 ‐1):	 3404,	 3301	 (NH2),	 3010,	 2981,	
2939,	2899	(CH	str.),	1666	(CO).	 	1H	NMR	(500	MHz,	CDCl3,	δ,	
ppm):	1.20	(t,	J	=	7	Hz,	3H,	CH3CH2),	3.84	(s,	3H,	CH3O),	4.10	(q,	J	
=	7	Hz,	2H,	CH3CH2),	4.97	(s,	1H,	H‐4),	6.41	(bs,	2H,	NH2),	8.17‐
6.33	(m,	9H,	Ar‐H).	13C	NMR	(125	MHz,	CDCl3,	δ,	ppm):	169.31	
(CO),	160.23	(2C),	152.01	(6C),	137.34	(10bC),	126.98	(10aC),	
125.76	 (9C),	 125.08	 (6aC),	 124.21	 (8C),	 122.13	 (7C),	 120.52	
(10C),	 119.91	 (4aC),	 103.30	 (5C),	 78.52	 (3C),	 59.52	 (CH3CH2),	
55.60	 (CH3O),	 40.98	 (4C),	 14.38	 (CH3CH2),	 146.57,131.21,	
129.75,	 119.66	 (Ar‐C).	 MS	 (EI,	m/z	 (%)):	 455	 (M++2,	 14.22),	
453	 (M+,	 15.99),	 298	 (100).	 Anal.	 calcd.	 for	 C23H20BrNO4:	 C,	
60.81;	H,	4.44;	N,	3.08.	Found:	C,	60.85;	H,	4.21;	N,	3.12	%.	

Ethyl	 2‐amino‐4‐(4‐methoxyphenyl)‐6‐methoxy‐4H‐benzo[h]	
chromene‐3‐carboxylate	 (8d):	 Color:	 Colorless	 needles.	
Crystallization:	From	ethanol/benzene.	Yield:	72	%.	M.p.:	159‐
160	 οC.	 FT‐IR	 (KBr,	 υ,	 cm	 ‐1):	 3414,	 3300	 (NH2),	 3014,	 2997,	
2963,	2875	(CH	str.),	1682	(CO).		

	



136	 El‐Agrody	et	al.	/	European	Journal	of	Chemistry	5	(1)	(2014)	133‐137	
	

	

+ Ar-CH=C

CN

X

..

4: X = CN
6: X = CO2Et

OH OH

C

Ar

X

N

O

Ar

X

NH

H

O

Ar

NH2

X

7: X = CN
8: X = CO2Et

-H2

1

OMe OMe
OMe

OMe

	
	

Scheme	3
	
	
MS	 (EI,	m/z	 (%)):	 405	 (M+,	29.33),	 299	 (100).	Anal.	 calcd.	

for	 C24H23NO5:	 C,	 71.10;	 H,	 5.72;	 N,	 3.45.	 Found:	 C,	 71.15;	 H,	
5.73;	N,	3.49	%.	

Ethyl	2‐amino‐4‐(3,4‐dimethoxyphenyl)‐6‐methoxy‐4H‐benzo	
[h]chromene‐3‐carboxylate	 (8f):	 Color:	 Light	 green	 crystals.	
Yield:	69%.	M.p.:	185‐186	οC.	FT‐IR	(KBr,	υ,	cm	‐1):	3412,	3310	
(NH2),	 3064,	 2937,	 2901,	 2833	 (CH	 str.),	 1676	 (CO).	 1H	 NMR	
(500	MHz,	CDCl3,	δ,	ppm):	1.16	(t,	J	=	7	Hz,	3H,	CH3CH2),	3.66	(s,	
3H,	CH3O),	3.73	(s,	3H,	CH3O),	3.88	(s,	3H,	CH3O),	4.02	(q,	J	=	7	
Hz,	2H,	CH3CH2),	4.99	(s,	1H,	H‐4),	7.72	(bs,	2H,	NH2),	8.27‐6.68	
(m,	8H,	Ar‐H).	13C	NMR	(125	MHz,	CDCl3,	δ,	ppm):	168.33	(CO),	
161.16	(2C),	151.04	(6C),	136.85	(10bC),	126.93	(10aC),	125.70	
(9C),	 124.03	 (6aC),	 123.65	 (8C),	 121.59	 (7C),	 120.53	 (10C),	
119.00	 (4aC),	 104.01	 (5C),	 76.49	 (3C),	 58.55	 (CH3CH2),	 55.70	
(CH3O),	55.46	(CH3O),	55.37	(CH3O),	39.93	(4C),	14.36	(CH3CH2),	
148.25,	147.08,	140.27,	121.30,	111.87,	111.53	(Ar‐C).	MS	 (EI,	
m/z	(%)):	435	(M+,	14.9),	299	(100).	Anal.	calcdç	for	C25H25NO6:	
C,	68.95;	H,	5.79;	N,	3.22.	Found:	C,	68.96;	H,	5.67;	N,	3.28	%.	
	
3.	Results	and	discussion		
	
3.1.	Synthesis		
	

Treatment	 of	4‐methoxy‐1‐naphthol	 (1)	with	 a	mixture	of	
aromatic	 aldehydes	 (2)	 and	 malononitrile	 (3)	 or	 α‐cyano	
cinnamonitriles	 (4)	 in	 ethanolic	 piperidine	 solution	 under	
microwave	irradiation	conditions	for	2	min	at	140	°C	afforded	
2‐amino‐4‐aryl‐6‐methoxy‐4H‐benzo[h]chromene‐3‐carbo‐
nitrile	 7a‐f	 (Scheme	 1).	 The	 reactions	 were	 controlled	 using	
TLC	technique.	

In	 a	 similar	 manner,	 treatment	 of	 4‐methoxy‐1‐naphthol	
(1)	with	aromatic	aldehydes	(2)	and	ethyl	cyanoacetate	(5)	or	
with	 ethyl	 α‐cyanocinnamates	 (6)	 under	 the	 same	 conditions	
afforded	 ethyl	 2‐amino‐4‐aryl‐6‐methoxy‐4H‐benzo[h]	
chromene‐3‐carboxylate	 8a‐d,	 f	 (Scheme	 2).	 The	 reactions	
were	controlled	using	TLC	 technique.	The	maximum	power	of	
microwave	irradiation	was	optimized	by	carrying	out	the	same	
reaction	at	different	Watt	powers.	Microwave	radiations	at	400	
W	 gave	 the	 highest	 yield,	 and	 therefore	microwave	 power	 of	
400	W	was	chosen	as	the	optimum	power.	

Attempts	 to	 react	 4‐methoxy‐1‐naphthol	 (1)	 with	 2,4‐
dimethoxybenzaldehyde	 (2e)	 and	 ethyl	 cyanoacetate	 (5)	 or	
with	 ethyl	 α‐cyanocinnamate	 (6e)	 in	 ethanolic	 piperidine	
solution	 under	 microwave	 irradiation	 conditions	 for	 2‐5	 min	
was	unsuccessful,	 the	ethyl	2‐amino‐4‐(2,4‐dimethoxyphenyl)‐
6‐methoxy‐4H‐benzo[h]chromene‐3‐carboxylate	 (8e)	was	 not	
formed.	This	may	be	due	to	the	steric	hindrance	of	the	methoxy	
group	at	position	2	of	the	2,4‐dimethoxy‐benzaldehyde.	

The	 formation	 of	 compounds	 7	 and	 8	 indicates	 that	 the	
naphtholate	anion	(C‐2)	of	compound	1	attack	at	the	β‐carbon	
of	compound	4	and	6	to	yield	an	acyclic	Michael	adduct,	which	
underwent	cyclization	to	give	compound	7	or	8	(Scheme	3).		

The	structures	of	compounds	7	and	8	were	established	on	
the	 basis	 of	 spectral	 data.	 The	 IR	 spectra	 of	 compounds	7a‐f	
showed	 the	 appearance	 of	 the	 a	 NH2	 stretch	 at	 υ	 3480‐3386,	
3398‐3329,	3284‐3199	cm,‐1	a	CN	stretch	at	υ	2194‐2186	cm,‐1	

while	a	NH2	stretch	at	υ	3414‐3404,	3330‐3300	cm‐1	and	a	CO	
stretch	at	υ	1682‐1666	cm‐1	for	compounds	8a‐d,f.	The	1H	and	
13	 C	 NMR	 spectra	 of	 compounds	7a‐f	 and	8a‐d,f	 revealed	 the	
presence	 of	 4H	 signals	 at	 δ	 5.13‐4.78	 (s,	 1H,	H‐4)	 and	 41.52‐
39.93	ppm	(C‐4).	In	compounds	8a‐c,f	the	ester	group	gave	1H	
signals	at	4.10‐4.02	(q,	J	=	7.0‐7.5	Hz,	2H,	CH2),	1.20‐1.13	(t,	J	=	
7.0‐7.5	Hz,	3H,	CH3)	with	 the	corresponding	 signals	 in	 the	 13C	
spectra	 at	 59.52‐58.55	 (CH2)	 and	 14.38‐14.30	 ppm	 (CH3)	
respectively.	 The	 13C	NMR‐DEPT	 spectra	 at	 45°,	 90°	 and	 135°	
and	 13C	 NMR‐APT	 spectra	 of	 compounds	 7	 and	 8	 provided	
additional	evidence	in	support	of	the	proposed	structures.	The	
13	 C	 NMR‐DEPT	 spectrum	 of	 compound	 7b	 at	 135о	 CH,	 CH3	
[positive	 (up)],	 CH2	 [negative	 (down)],	 revealed	 the	 following	
signals	at	δ	55.72	(CH3	↑),	40.74	(C‐4	↑),	while	at	90°	only	CH	
signals	are	positive	(up)	and	showed	δ	40.74	(C‐4	↑)	and	at	45°	
(CH,	CH2	and	CH3	positive)	revealed	signals	at	δ	55.72	(CH3	↑),	
40.74	ppm	(C‐4	↑).	The	13	C	NMR‐DEPT	spectrum	of	compound	
8b	 at	 135о	 CH,	 CH3	 [positive	 (up)],	 CH2	 [negative	 (down)],	
revealed	the	following	signals	at	δ	58.62	(CH2	↓),	40.08	(C‐4	↑),	
14.30	(CH3↑	),	while	at	90°	only	CH	signals	are	positive	(up)	and	
showed	 δ	 40.08	 ppm	 (C‐4	 ↑)	 and	 at	 45°	 (CH,	 CH2	 and	 CH3	
positive)	 revealed	 signals	 at	 δ	 58.62	 (CH2	 ↑),	 40.08	 (C‐4	 ↑),	
14.30	 ppm	 (CH3	 ↑).	 In	 addition,	 the	 1H	 NMR	 spectra	 for	
compounds	7a	 and	8a	 showed	NH2	protons	resonated	at	7.14	
(sharp	 singlet)	 and	 7.49	 (broad	 singlet	 lower	 field).	 This	
deshielding	is	a	result	of	replacement	of	CN	group	in	compound	
7a	by	C=O	group	in	compound	8a	whose	C=O	anisotropy	would	
deshield	 these	 protons	 and	 in	 addition	 of	 the	 involvement	 of	
these	 protons	 in	 hydrogen	 bonding	with	 the	 C=O	 group.	 This	
was	 supported	 by	X‐ray	 single	 crystal	 data	 [74,76].	 The	mass	
spectra	 of	 compounds	7	and	8	gave	 also	 additional	 evidences	
for	the	proposed	structures.	
	
4.	Conclusions		
	

In	 this	 article,	 we	 report	 the	 synthesis	 of	 some	 4H‐
benzo[h]chromene	 derivatives	 under	 Microwave	 irradiation	
conditions.	The	structures	of	these	compounds	were	elucidated	
on	 the	 basis	 of	 spectral	 data,	 IR,	 1H	NMR,	 13C	NMR,	 13C	NMR‐
DEPT	and	MS	data.	The	newly	synthesized	compounds	7	and	8	
will	be	tested	against	tumor	cell	lines,	also	for	DNA	extractions	
and	will	be	published	later.	
	
Acknowledgements		
	

This	 study	 was	 supported	 by	 the	 King	 Abdulaziz	 City	 for	
Science	 and	 Technology	 (KACST),	 No.	 A‐S‐12‐097 .	 We	 also	
deeply	 thank	Mr.	 Ali	 Y.	 A.	 Alshahrani	 for	making	 the	 1H	NMR	
and	13C	NMR	spectra.	
	
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