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European	Journal	of	Chemistry	3	(3)	(2012)	273‐278	

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

DOI:10.5155/eurjchem.3.3.273‐278.605	

	
	

	

	

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

	 	 	

Synthesis	of	some	new	pyrazolylfuropyrimidinethiones	and	
triazolofuropyrimidinethiones	

Mohamed	Abdel	Megid	Abdel‐Hamid,	Azza	Mohamed	Elkazak*,		
Magdy	Hamed	Sead	and	Osama	Farouk	Mohamed	

Department	of	Chemistry,	Faculty	of	Education,	Ain	Shams	University,	Roxy,	11711,	Cairo,	Egypt	

*Corresponding	author	at:	Department	of	Chemistry,	Faculty	of	Education,	Ain	Shams	University,	Roxy,	11711,	Cairo,	Egypt.	Tel.:	+2.0100.6422648;		
fax:	+2.02.2581243.	E‐mail	address:	az_azelkazak@yahoo.com		(A.M.	Elkazak).	

	
	

	 	

	 	 	
ARTICLE	INFORMATION	 	 ABSTRACT	
Received:	29	February	2012	
Received	in	revised	form:05	April	2012	
Accepted:	15	April	2012	
Online:	30	September	2012	

KEYWORDS	

	 Some	 novel	 pyrazolylfuropyrimidinethiones	 were	 synthesized	 from	 cyclocondensation	 of
4‐hydrazino‐5,6‐diphenylfuro	[2,3‐d]	pyrimidine‐2(1H)‐thione	(3)	with	different	enaminones
and	 1,3‐dicarbonyl	 compounds.	 Whereas	 the	 furotriazolo‐pyrimidinethiones	 were
synthesized	 from	reaction	of	 compound	3	with	benzoyl	 chloride,	p‐chlorobenzaldehyde	and
carbon	 disulphide.	 Furthermore,	 furotetrazolo‐pyrimidinethione	 and	 ditetrazolofuro
pyrimidine	were	synthesized.	

Triazoles	
Pyrazoles	
Tetrazoles	
Enaminones	
Ditetrazoles	
Furopyrimidines	

	
1.	Introduction	
	

Polysubstituted	 furans	 are	 important	 heterocyclic	
molecules	 due	 to	 practical	 utility	 as	 a	 recurring	 unit	 in	many	
natural	 and	 medicinal	 molecules.	 Many	 of	 the	 naturally	
occurring	 furans	 have	 shown	 interesting	 biological	 activities.	
On	the	other	hand,	pyrimidines,	being	integral	part	of	DNA	and	
RNA,	 exhibit	 diverse	 pharmacological	 properties	 such	 as	
effective	 bactericides,	 fungicides,	 viricides,	 insecticides	 and	
posses	 significant	 therapeutic	 values	 [1].	 Motivated	 by	 these	
facts,	the	present	investigation	deals	with	combination	of	furan	
and	 pyrimidine	 moieties	 in	 a	 molecular	 framework.	
Furopyrimidine	 derivatives	 are	 an	 important	 class	 of	
heterocyclic	 compounds	 in	pharmaceutical	discovery	 research	
[2,3].	 They	 showed	 antifungal	 [4],	 antifolate	 [5],	 antibacterial	
[6],	antitumor	[7],	antiviral	[8],	and	anti	HCMV	[9]	(antihuman	
cytomegalovirus).	As	a	part	of	our	program	directed	to	develop	
the	chemistry	of	enaminones	[10],	and	pyrimidines	[11‐16],	the	
present	 investigation	 deals	 with	 the	 use	 of	 2‐amino‐4,5‐
diphenylfuran‐3‐carbonitrile	(1)	[17],	as	a	starting	material	for	
the	synthesis	of	the	target	pyrazolylfuropyrimidinethiones	and	
furotriazolopyrimidinethiones.	
 
2.	Experimental	
	
2.1.	Instrumentation	
		

All	 melting	 points	 were	 measured	 on	 Stuart	 SMP‐3	 and	
were	uncorrected.	The	IR	spectra	were	recorded	on	FT‐IR	Jasco	
4000	 spectrophotometer	 using	 KBr	wafer	 technique.	 1H	NMR	
spectra	 were	measured	 on	 Varian	 Gemini	 spectrophotometer	
200	MHz	and	Varian	Mercury	VX‐300	NMR	spectrometer	using	
TMS	 (δ	 ppm)	 as	 an	 internal	 standard.	 13C	 NMR	 spectra	 were	

measured	 at	 75.00	 MHz	 in	 dimethylsulphoxide	 (DMSO‐d6).	
Mass	 spectra	were	 obtained	 using	 GC‐MS	 Shimadzu	Qp‐2010,	
GAS‐chromatograph	 (GC‐14A)	 and	 JEOL‐JMS‐AX500	 mass	
spectrometer.	 2‐Amino‐4,5‐diphenylfuran‐3‐carbonitrile	 (1)	
was	prepared	according	to	the	reported	method	[17].	
	
2.2.	Synthesis 
	
2.2.1.	5,6‐Diphenylfuro	[2,3‐d]	pyrimidine‐2,4(1H,3H)‐
dithione	(2)	
	

A	mixture	of	1	(0.01	mol,	2.6	g)	and	carbon	disulphide	(0.02	
mol,	 1.2	 mL)	 in	 ethanolic	 potassium	 hydroxide	 (0.56	 g	 in	 20	
mL)	was	heated	under	reflux	for	3	h.	The	reaction	mixture	was	
cooled;	the	solid	salt	was	dissolved	in	water	and	acidified	with	
few	 drops	 of	 concentrated	 hydrochloric	 acid	 .The	 solid	
obtained	was	 filtered	off	 and	 recrystallized	 from	DMF	 to	 give	
compound	2	 as	 yellow	 crystals	 (Scheme	 1).	 Yield:	 72%.	M.p.:	
276‐278	 °C.	 FT‐IR	 (KBr,	 cm‐1):	 3345,	 3200	 (2	 NH),	 3054	
(CHaromatic),	 1594‐1509	 (C=N	 and	 C=C),	 1243,	 1206	 (2	 C=S),	
1072	(C‐O‐).	MS	(EI,	m/z,	(%)):	336	(M,	88),	277	(30),	259	(2),	
218	 (3),	 178	 (5),	 118	 (5),	 77	 (100),	 59	 (9).	 Anal.	 calcd.	 for	
C18H12N2OS2:	 C,	 64.26;	 H,	 3.60;	 N,	 8.33;	 S,	 19.06.	 Found:	 C,	
64.30;	H,	3.70;	N,	8.40;	S,	19.10%.	
	 
2.2.2.	4‐Hydrazino‐5,6‐diphenylfuro[2,3‐d]pyrimidin‐2(1H)‐
thione	(3)	
 

A	mixture	 of	 2	 (0.01	 mol,	 3.36	 g)	 and	 hydrazine	 hydrate	
(0.01	 mol,	 0.5	 mL)	 in	 absolute	 ethanol	 (20	 mL)	 was	 heated	
under	 reflux	 for	 2	 h.	 The	 solid	 obtained	 was	 filtered	 off	 and	
recrystallized	 from	 ethanol	 to	 give	 compound	 3	 as	 yellow	
crystals	(Scheme	1).	Yield:	74%.	M.p.:	215‐217	°C.		



274	 Abdel‐Hamid	et	al.	/	European	Journal	of	Chemistry	3	(3)	(2012)	273‐278	
	

	

 
	

Scheme	1
	

	
FT‐IR	 (KBr,	 cm‐1):	 3590‐3158	 (NH2,	 2NH),	 3052	 (CHarom.),	

1567‐1504	 (C=N	 and	 C=C),	 1217	 (C=S),	 1098	 (C‐O‐).	 1H	NMR	
(200	MHz,	DMSO‐d6,	δ,	ppm):	6.17	(br.s,	2H,	NH2	exchangeable	
with	 D2O),	 6.49	 (s,	 1H,	 NHhydrazine),	 6.90‐8.06	 (m,	 10H,	 Ar‐H),	
9.86	 (s,	 1H,	 NHpyrimidine).	 MS	 (EI,	m/z,	 (%)):	 334	 (M,	 28),	 336	
(21),	 304	 (7),	 229	 (55),	 101	 (21),	 77	 (100).	 Anal.	 calcd.	 for	
C18H14N4OS:	C,	64.65;	H,	4.22;	N,	16.75;	S,	9.59.	Found:	C,	64.80;	
H,	4.30;	N,	16.60;	S,	9.70%.	
	
2.2.3.	4‐(4,5‐Diphenyl‐1H‐pyrazol‐1‐yl)‐5,6‐diphenylfuro	
[2,3‐d]pyrimidine‐2(1H)‐thione	(5)	
	

A	mixture	of	3	(0.01	mol,	3.34	g)	and	3‐dimethylamino‐1,2‐
diphenylpropen‐1‐one	 (0.01	 mol,	 2.51	 g)	 in	 absolute	 ethanol	
(20	 mL)	 containing	 few	 drops	 of	 triethylamine	 was	 heated	
under	reflux	for	3	h.	After	cooling,	the	solid	product	so	formed,	
was	 collected	 and	 recrystallized	 from	 ethanol	 to	 give	
compound	5	 as	 brown	 crystals	 (Scheme	 1).	 Yield:	 71%.	M.p.:	
167‐169	°C.	FT‐IR	(KBr,	cm‐1):	3418	(NH),	3055	(CHarom.),	1593‐
1545	 (C=N	 and	 C=C),	 1185	 (C=S),	 1069	 (C‐O‐).	 MS	 (EI,	m/z,	
(%)):	522	(M,	17),	520	(100),	505	(58),	494	(2),	490	(40),	478	
(1),	317	(24),	231	(16),	214	(12),	205	(7),	154	(11),	105	(27).	
Anal.	calcd.	 for	C33H22N4OS:	C,	75.84;	H,	4.24;	N,	10.72;	S,	6.14.	
Found:	C,	75.90;	H,	4.20;	N,	10.60;	S,	6.20%.	
 
2.2.4.	4‐(4‐Benzoylamino‐1H‐pyrazol‐1‐yl)‐5,6‐diphenylfuro	
[2,3‐d]pyrimidine‐2(1H)‐thione	(7)	
	

A	 mixture	 of	 3	 (0.01	 mol,	 3.34	 g)	 and	 4‐
methylidenedimethylamino‐2‐phenyl‐1,3‐oxazol‐5‐one	 (0.01	

mol,	2.16	g)	 in	absolute	ethanol	(20	mL)	containing	few	drops	
of	triethylamine	was	heated	under	reflux	for	3	h.	After	cooling,	
the	 solid	 product	 so	 formed	 was	 collected	 by	 filtration	 and	
recrystallized	 from	 ethanol	 to	 give	 compound	 7	 as	 yellow	
crystals	(Scheme	1).	Yield:	74%.	M.p.:	222‐224	°C.	FT‐IR	(KBr,	
cm‐1):	 3421,	 3276	 (2	 NH),	 3061	 (CHarom.),	 1672	 (C=O),	 1615‐
1577	 (C=N	 and	 C=C),	 1231	 (C=S),	 1094	 (C‐O‐).	 1H	 NMR	 (200	
MHz,	DMSO‐d6,	 δ,	 ppm):	 5.58	 (s,	 1H,	H‐5pyrazole),	 7.21‐7.90	 (m,	
15H,	 Ar‐H),	 7.96	 (s,	 1H,	 H‐3pyrazole),	 8.08	 (s,	 1H,	 NHpyrimidine	
exchangeable	 with	 D2O),	 10.38	 (s,	 1H,	 NHamide	 exchangeable	
with	D2O).	MS	 (EI,	m/z,	 (%)):	 487	 (M‐2,	 3),	 383	 (2),	 274	 (4),	
271	(4),	218	(4),	215	(3),	154	(3),	120	(7),	105	(25),	77	(63),	50	
(100).	Anal.	calcd.	for	C28H19N5O2S:	C,	68.70;	H,	3.91;	N,	14.31;	S,	
6.55.	Found:	C,	68.60;	H,	3.80;	N,	14.30;	S,	6.60%.	
 	
2.2.5.	5,6‐Diphenyl‐4‐(4‐methyl‐6‐phenylpyrazolo[3,4‐c]	
pyrazol‐1(6H)‐yl)‐3,4‐dihydro‐furo[2,3‐d]pyrimidine‐2(1H)‐
thione	(9)	
	

A	 mixture	 of	 3	 (0.01	 mol,	 3.34	 g)	 and	 4‐
methylidenedimethylamino‐1‐phenylpyrazol‐5‐one	 (0.01	 mol,	
2.29	 g)	 in	 absolute	 ethanol	 (20	 mL)	 containing	 few	 drops	 of	
triethylamine	was	heated	under	reflux	for	3	h.	After	cooling,	the	
solid	product	so	formed	was	filtered	off	and	recrystallized	from	
ethanol	 to	 give	 compound	 9	 as	 yellow	 crystals	 (Scheme	 1).	
Yield:	 64%.	 M.p.:	 232‐234	 °C.	 FT‐IR	 (KBr,	 cm‐1):	 3276	 (NH),	
3055	(CHarom.),	2969	(CHaliph.),	1599‐1544	(C=N	and	C=C),	1262	
(C=S),	1079	(C‐O‐).		

	
	



Abdel‐Hamid	et	al.	/	European	Journal	of	Chemistry	3	(3)	(2012)	273‐278	 275	
 

	

 
	

Scheme	2
	
	

MS	 (EI,	m/z,	 (%)):	 481	 (M‐19,	 6),	 344	 (11),	 322	 (6),	 317	 (3),	
218	(3),	185	(100),	183	(14),	156	(16),	77	(33).	Anal.	calcd.	for	
C29H20N6OS:	C,	69.58;	H,	4.03;	N,	16.79;	S,	6.41.	Found:	C,	69.60;	
H,	4.10;	N,	16.70;	S,	6.30%. 	
		
2.2.6.	5,6‐Diphenyl‐4‐(pyrazolo[3,4‐b]indol‐1‐yl)‐furo[2,3‐d]	
pyrimidine‐2(1H)‐thione	(11)	
	

A	 mixture	 of	 3	 (0.01	 mol,	 3.34	 g)	 and	 3‐
methylidenedimethylaminoindol‐2(1H)‐one	 (0.01	mol,	 1.88	 g)	
in	 absolute	 ethanol	 (20	 mL)	 containing	 few	 drops	 of	
triethylamine	was	heated	under	reflux	for	3	h.	After	cooling,	the	
solid	product	so	formed	was	filtered	off	and	recrystallized	from	
ethanol	 to	 give	 compound	 11	 as	 brown	 crystals	 (Scheme	 1).	
Yield:	76%.	M.p.:	238‐240	°C.	FT‐IR	(KBr,	cm‐1):	3400,	3312	(2	
NH),	 3055	 (CHarom.),	 1594‐1541	 (C=N	 and	 C=C),	 1238	 (C=S),	
1137	 (C‐O‐).	 1H	NMR	 (300	MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.19‐7.57	
(m,	 14H,	 Ar‐H),	 7.96	 (s,	 1H,	 H‐3pyrazole),	 8.64	 (s,	 1H,	 NHindole	
exchangeable	with	D2O),	10.95	(s,	1H,	NHpyrimidine	exchangeable	
with	D2O).	MS	 (EI,	m/z,	 (%)):	 460	 (M+1,	 1),	 344	 (2),	 305	 (2),	
265	 (1),	 241	 (7),	 218	 (7),	 203	 (100),	 194	 (8),	 178	 (15),	 105	
(31%).	Anal.	calcd.	for	C27H17N5OS:	C,	70.57;	H,	3.73;	N,	15.24;	S,	
6.98.	Found:	C,	70.50;	H,	3.80;	N,	15.30;	S,	6.90%.	
	
2.2.7.	5,6‐Diphenyl‐4‐(3‐hydroxy‐5‐oxo‐1H,4H‐pyrazol‐1‐yl)‐
furo[2,3‐d]pyrimidine‐2(1H)‐thione	(12)	
	

A	 mixture	 of	 3	 (0.01	 mol,	 3.34	 g)	 and	 diethyl	 malonate	
(0.01	mol,	1.5	mL)	in	absolute	ethanol	(20	mL)	containing	few	
drops	 of	 triethylamine	was	 heated	 under	 reflux	 for	 3	 h.	After	
cooling,	 the	 solid	 obtained	was	 filtered	 off	 and	 recrystallized	
from	DMF	to	give	compound	12	as	white	crystals	(Scheme	2).	
Yield:	 74%.	 M.p.:	 244‐246	 °C.	 FT‐IR	 (KBr,	 cm‐1):	 3441	 (OH),	
3298	 (NH),	 3063	 (CHaromatic),	 2924	 (CHaliphatic),	 1666	 (C=O),	
1620‐1573	 (C=N	 and	 C=C),	 1230	 (C=S),	 1099	 (C‐O‐).	 1H	NMR	
(300	MHz,	DMSO‐d6,	 δ,	 ppm):	 5.56	 (s,	 2H,	CH2),	 7.09‐7.37	 (m,	
10H,	Ar‐H),	 8.05	 (s,	 1H,	NH	 exchangeable	with	D2O),	10.34	 (s,	
1H,	OH	exchangeable	with	D2O).	13C	NMR	(75	MHz,	DMSO‐d6,	δ,	
ppm):	 	 34.5	 (CH2),	 82.5	 (bridged	 C3‐furan),	 125.5,	 127.2,	
128.3(2),	128.4	(2)	(corresponding	to	six	phenyl	carbons),	131	

(C4‐furan),	132.1,	136.3(corresponding	to	two	phenyl	carbons),	
143.4	 (bridged	 C2‐furan),	 153.8	 (C5‐furan),	 162.3	 (2)	
(corresponding	to	C‐OH,	pyrazole	and	C=N,	pyrimidine),	162.7	
(C=O)	and	168.6	(C=S).	MS	(EI,	m/z,	(%)):	402	(M,	1),	404	(1),	
325	 (1),	 307	 (1),	 230	 (1),	 178	 (1),	 154	 (2C6H5,	 1)	 105	 (3),	
77(100).	 Anal.	 calcd.	 for	 C21H14N4O3S:	 C,	 62.68;	 H,	 3.51;	 N,	
13.92;	S,	7.97. Found:	C,	62.80;	H,	3.40;	N,	13.80;	S,	7.90.		
		
2.2.8.	5,6‐Diphenyl‐4‐(3‐hydroxy‐5‐methyl‐1H‐pyrazol‐1‐yl)‐
furo[2,3‐d]pyrimidine‐2(1H)‐thione	(13)	
		

A	 mixture	 of	 3	 (0.01	 mol,	 3.34	 g)	 and	 ethyl	 acetoacetate	
(0.01	mol,	1.3	mL)	in	absolute	ethanol	(20	mL)	containing	few	
drops	 of	 triethylamine	was	 heated	 under	 reflux	 for	 3	h.	 After	
cooling,	 the	 solid	 obtained	 was	 filtered	 off	 and	 recrystallized	
from	dioxan	 to	give	 compound	13	as	brown	crystals	 (Scheme	
2).	Yield:	64%.	M.p.:	264‐266	°C.	FT‐IR	(KBr,	cm‐1):	3600‐3200	
(OH,	NH),	3059	 (CHarom.),	 2978	 (CHaliph.),	 1602‐1570	 (C=N	and	
C=C),	1261	 (C=S),	 1068	 (C‐O‐).	MS	 (EI,	m/z,	 (%)):	400	 (M,	 1),	
384	(1),	372	(1),	366	(1),	356	(1),	323	(1),	246	(3),	154	(	1),	77	
(6),	61	(100),	42	(15).	Anal.	calcd.	for	C22H16N4O2S:	C,	65.99;	H,	
4.03;	 N,	 13.99;	 S,	 8.01. Found:	 C,	 65.90;	 H,	 4.10;	 N,	 13.90;	 S,	
8.10%.	
		
2.2.9.	4‐(3,5‐Dimethyl‐1H‐pyrazol‐1‐yl)‐5,6‐diphenylfuro	
[2,3‐d]pyrimidine‐2(1H)‐thione	(14)	
	

A	mixture	 of	3	 (0.01	mol,	 3.34	 g)	 and	 acetylacetone	 (0.01	
mol,	1	mL)	in	absolute	ethanol	(20	mL)	containing	few	drops	of	
triethylamine	was	heated	under	reflux	for	3	h.	After	cooling,	the	
solid	obtained	was	filtered	off	and	recrystallized	 from	ethanol	
to	give	14	as	yellow	crystals	(Scheme	2).	Yield:	74%.	M.p.:	121‐
123	 °C.	 FT‐IR	 (KBr,	 cm‐1):	 3251	 (NH),	 3059	 (CHarom.),	 2974	
(CHaliph.),	1589‐1551	(C=N	and	C=C),	1250	(C=S),	1057	(C‐	O‐).	
1H	 NMR	 (200	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 3.34	 (s,	 3H,	 CH3‐C5	
pyrazole),	 4.27	 (s,	 3H,	 CH3‐C3	 pyrazole),	 6.54	 (s,	 1H,	 CH	
pyrazole),	7.15‐7.73	(m,	10H,	Ar‐H),	11.98	(s,	1H,	NH).	MS	(EI,	
m/z,	(%)):	396	(M‐2,	10),	370	(2),	358	(7),	357	(7),	321	(4),	292	
(9),	244	(10),	154	(7),	106	(14),	77	(55),	59	(3),	43	(100).		

	



276	 Abdel‐Hamid	et	al.	/	European	Journal	of	Chemistry	3	(3)	(2012)	273‐278	
	

	

N
H

N

NHNH2

SOPh

Ph

(3)

PhCOCl

Pyridine
N
H

S

N

NN

O

Ph Ph

Ph

(16)

ClOHC

Glacial AcOH N
H

S

N

NHN

Cl
O

Ph

Ph

PhCOCH3

N
H

S

N

NHN

CH3

OPh

Ph
Ph

(18)

CS2

KOH N
H

S

N

NHN
S

O

Ph

Ph

(19)

N
H

S

N
N
NN

O

Ph

Ph

NaNO2

AcOH

(20)

(17)

 
	

Scheme	3
	
	

Anal.	calcd.	 for	C23H18N4OS:	C,	69.33;	H,	4.55;	N,	14.06;	S,	8.05.	
Found:	C,	69.40;	H,	4.60;	N,	14.10;	S,	8.10%.	
 	
2.2.10.	4‐[5‐Amino‐4‐carboxamido‐3‐(4‐chlorophenyl)‐1H‐
pyrazol‐1‐yl]‐5,6‐diphenyl‐furo[2,3‐d]pyrimidine‐2(1H)‐
thione	(15)	
 

A	mixture	of	3	 (0.01	mol,	3.34	g)	and	p‐chlorobenzlidene‐
cyanoacetamide	 (0.01	 mol,	 2	 g)	 in	 absolute	 ethanol	 (20	 mL)	
containing	few	drops	of	triethylamine	was	heated	under	reflux	
for	 3	 h.	 After	 cooling,	 the	 solid	 obtained	was	 filtered	 off	 and	
recrystallized	 from	 ethanol	 to	 give	 compound	 15	 as	 red	
crystals	 (Scheme	2).	Yield:	74%.	M.p.:	235‐237	°C.	FT‐IR	(KBr,	
cm‐1):	 3600‐3200	 (2NH,	 2NH2),	 3059	 (CHarom.),	 2924	 (CHaliph.),	
1639	(C=O),	1593‐1554	(C=N	and	C=C),	1219	(C=S),	1092	(C‐O‐
).	MS	(EI,	m/z,	(%)):	540	(M,	11),	112	(4),	106	(5),	77	(14),	61	
(100),	44	(76).	Anal.	calcd.	for	C28H21N6O2SCl:	C,	62.16;	H,	3.91;	
N,	15.53;	S,	5.93;	Cl,	6.55.	Found:	C,	62.20;	H,	3.80;	N,	15.50;	S,	
6.00;	Cl,	6.60%.	
		
2.2.11.	3,8,9‐Triphenylfuro[2`,3`:4,5]pyrimido[6,1‐c]‐1,2,4‐
triazole‐5(6H)‐thione	(16)	
	

A	mixture	of	3	(0.01	mol,	3.34	g)	and	benzoyl	chloride	(0.01	
mol	1.2	mL)	 in	pyridine	(20	mL)	was	heated	on	boiling	water	
bath	for	3	h.	The	mixture	was	left	to	cool	at	room	temperature,	
and	 then	 poured	 onto	 crushed	 ice	 containing	 HCl,	 the	 solid	
obtained	 was	 filtered	 off	 and	 recrystallized	 from	 benzene	 to	
give	 compound	16	 as	white	 crystals	 (Scheme	 3).	 Yield:	 81%.	
M.p.:	132‐134	°C.	FT‐IR	(KBr,	cm‐1):	3354	(NH),	3065	(CHarom.),	
1591‐1503	 (C=N	 and	 C=C),	 1205	 (C=S),	 1065	 (C‐O‐).	 MS	 (EI,	
m/z,	 (%)):	 422	 (M+2,	 45),	 345	 (25),	 336	 (40),	 286	 (42),	 167	
(70),	 162	 (57),	 79.(85),	 77	 (84),	 69	 (100).	 Anal.	 calcd.	 for	
C25H16N4OS:	C,	71.41;	H,	3.84;	N,	13.32;	S,	7.63. Found:	C,	71.50;	
H,	3.80;	N,	13.40;	S,	7.50%.		
	
	

2.2.12.	3‐(4‐Chlorophenyl)‐2,3‐dihydro‐8,9‐diphenylfuro	
[2`,3`:4,5]pyrimido[6,1‐c]‐1,2,4‐triazole‐5(6H)‐thione	(17)	
	

A	mixture	of	3	(0.01	mol,	3.34	g)	and	p‐chlorobenzaldehyde	
(0.01	 mol,	 1.41	 g)	 in	 glacial	 acetic	 acid	 (20	 mL)	 was	 heated	
under	 reflux	 for	 2	 h.	 After	 cooling,	 the	 solid	 obtained	 was	
filtered	 off	 and	 recrystallized	 from	 ethanol	 to	 give	 compound	
17	as	red	crystals	(Scheme	3).	Yield:	85%.	M.p.:	>300	°C.	FT‐IR	
(KBr,	cm‐1):	3424,	3329	(2NH),	3025	(CHarom.),	1613‐1544	(C=N	
and	C=C),	1213	(C=S),	1086	(C‐O‐).	1H	NMR	(200	MHz,	DMSO‐
d6,	δ,	ppm):	6.38	(s,	1H,	C3‐H),	7.52‐7.58	(m,	14H,	Ar‐H),	8.29	(s,	
1H,	 NH,	 triazole	 exchangeable	 with	 D2O),	 10.80	 (s,	 1H,	 NH,	
pyrimidine	 exchangeable	 with	 D2O).	 MS	 (EI,	 m/z,	 (%)):	 459	
(M+2,	27),	345	(49),	303	(27),	105	(85),	77	(72),	51	(100).	Anal.	
calcd.	 for	C25H17N4OSCl:	C,	65.71;	H,	3.75;	N,	12.26;	S,	7.02;	Cl,	
7.76. Found:	C,	65.80;	H,	3.70;	N,	12.30;	S,	7.10;	Cl,	7.60%.		
	
2.2.13.	3‐Methyl‐3,8,9‐triphenylfuro[2`,3`:4,5]pyrimido[6,1‐
c]‐1,2,4‐triazole‐5(6H)‐thione	(18)	
	

A	mixture	of	3	 (0.01	mol,	3.34	g,)	and	acetophenone	(0.01	
mol,	 1.2	mL)	 in	 glacial	 acetic	 acid	 (20	mL)	was	 heated	 under	
reflux	for	3	h.	After	cooling,	 the	solid	obtained	was	filtered	off	
and	recrystallized	from	ethanol	to	give	compound	18	as	yellow	
crystals	(Scheme	3).	Yield:	89%.	M.p.:	254‐255	°C.	FT‐IR	(KBr,	
cm‐1):	3434,	3340	 (2NH),	3043	(CHarom.),	2929	(CHaliph.),	1578‐
1523	 (C=N	 and	 C=C),	 1210	 (C=S),	 1073	 (C‐O‐).	 1H	 NMR	 (200	
MHz,	DMSO‐d6,	δ,	ppm):	2.12	(s,	3H,	CH3),	7.38‐7.8	(m,	15H,	Ar‐
H),	 9.32	 (s,	 1H,	NH	 triazole	 exchangeable	with	D2O),	 10.90	 (s,	
1H,	NH	pyrimidine	exchangeable	with	D2O).	MS	(EI,	m/z,	(%)):	
435	 (M‐1,	 1),	 421	 (1),	 344	 (1),	 282	 (2),	 103	 (100),	 77	 (99.9).	
Anal.	calcd.	for	C26H20N4OS:	C,	71.54;	H,	4.62;	N,	12.83;	S,	7.35.	
Found:	C,	71.40;	H,	4.70;	N,	12.70;	S,	7.40%.		
	
	
	
	



Abdel‐Hamid	et	al.	/	European	Journal	of	Chemistry	3	(3)	(2012)	273‐278	 277	
 

	  

(2)

O N

N

SR

Ph

Ph

SR

RX

(21a), R = Et, X = I
(21b), R = CH2COOEt, X = Cl

N2H4.H2O

O

Ph

Ph

N
N
NN

N
N N

N

(23)

HNO2
0o C

In case of 21a
O N

N

NHNH2

NHNH2

Ph

Ph

(22)

N
H

NH

S

SO

Ph

Ph

 
	

Scheme	4
 

	
2.2.14.	8,9‐Diphenylfuro[2`,3`:4,5]pyrimido[6,1‐c]‐1,2,4‐
triazole‐3,5(2H,6H)‐dithione	(19)	
 

A	mixture	 of	3	 (0.01	mol,	 3.34	 g)	 carbon	disulphide	 (0.01	
mol,	 0.6	 mL)	 and	 potassium	 hydroxide	 (0.01	 mol,	 0.56	 g)	 in	
ethanol	(20	mL)	was	heated	under	reflux	for	3	h.	After	cooling,	
the	 solid	 obtained	 upon	 neutralization	 with	 dilute	 HCl	 was	
filtered	off	and	recrystallized	from	dioxan	to	give	compound	19	
as	yellow	crystals	(Scheme	3).	Yield:	72%.	M.p.:	256‐258	°C.	FT‐
IR	 (KBr,	 cm‐1):	 3396,	 3210	 (2NH),	 3059	 (CHarom.),	 1596‐1511	
(C=N	 and	C=C),	 1213,	 1165	 (2C=S),	 1066	 (C‐O‐).	MS	 (EI,	m/z,	
(%)):	360	(M‐O,	13),	359	(20),	219	(20),	218	(17),	77	(47),	76	
(100).	Anal.	calcd.	for	C19H12N4OS2:	C,	60.62;	H,	3.21;	N,	14.88;	S,	
17.04.	Found:	C,	60.70;	H,	3.20;	N,	14.90;	S,	16.90%.	
	
2.2.15.	8,9‐Diphenylfuro[2`,3`:4,5]pyrimido[1,6‐d]‐1,2,3,4‐
tetrazole‐5(6H)‐thione	(20)	
	

A	mixture	of	3	 (0.01	mol,	3.34	g)	and	sodium	nitrite	(0.01	
mol,	0.69	g)	 in	glacial	acetic	acid	(20	mL)	was	stirred	at	room	
temperature	for	4	h.	The	solid	product	so	formed	was	collected	
and	recrystallized	from	ethanol	to	give	compound	20	as	yellow	
crystals	 (Scheme	3).	Yield:	74%.	M.p.:	118‐120	°C.	FT‐IR	(KBr,	
cm‐1):	 3390	 (NH),	 3058	 (CHarom.),	 1593‐1570	 (C=N	 and	 C=C),	
1249	(C=S),	1064	(C‐O‐).	MS	(EI,	m/z,	(%)):	347	(M+2,	2),	311	
(1),	 297	 (2),	 270	 (3),	 216	 (5),	 155	 (6),	 140	 (6),	 105	 (80),	 77	
(100).	Anal.	calcd.	for	C18H11N5OS:	C,	62.59;	H,	3.21;	N,	20.28;	S,	
9.28.	Found:	C,	62.70;	H,	3.20;	N,	20.30;	S,	9.20%. 	
	
2.2.16.	2,4‐Diethylthio‐5,6‐diphenylfuro[2,3‐d]pyrimidine	
(21a)	
	

A	mixture	of	2	(0.01	mol,	3.36	g),	ethyl	iodide	(0.02	mol,	1.6	
mL)	 and	 aqueous	 potassium	 hydroxide	 in	 DMF	 (20	 mL)	 was	
heated	 under	 reflux	 for	 3	 h.	 The	 mixture	 was	 left	 to	 cool	 at	
room	temperature,	and	then	poured	onto	crushed	ice,	the	solid	
obtained	was	filtered	off	and	recrystallized	from	ethanol‐H2O	to	
give	compound	21a	 as	white	 crystals	 (Scheme	4).	Yield:	83%.	
M.p.:	 100‐102	 °C.	 FT‐IR	 (KBr,	 cm‐1):	 3054	 (CHarom.),	 2969	
(CHaliph.),	1601‐1573	(C=N	and	C=C),	1058	(C‐O‐).	1H	NMR	(200	
MHz,	DMSO‐d6,	δ,	ppm):	1.21	(t,	3H,	CH3),	1.36	(t,	3H,	CH3‐CH2),	
3.14	(q,	2H,	CH2‐CH3),	3.40	(q,	2H,	CH2),	7.33‐7.51	(m,	10H,	Ar‐
H).	MS	(EI,	m/z,	(%)):	392	(M,	43),	393	(11),	394	(6),	377	(7),	
363	 (7),	 331	 (6),	 105	 (16),	 77	 (41),	 69	 (100).	 Anal.	 calcd.	 for	
C22H20N2OS2:	 C,	 67.32;	 H,	 5.14;	 N,	 7.14;	 S,	 16.34. Found:	 C,	
67.30;	H,	5.20;	N,	7.20;	S,	16.50%.	 
		
2.2.17.	2,4‐Dicarbethoxymethylthio‐5,6‐diphenylfuro[2,3‐d]	
pyrimidine	(21b)	
 

A	mixture	 of	 2	 (0.01	 mol,	 3.36	 g)	 and	 ethylchloroacetate	
(0.02	 mol,	 2.1	 mL)	 in	 DMF	 (20	 mL)	 containing	 few	 drops	 of	
triethylamine	 was	 heated	 under	 reflux	 for	 4	 h.	 The	 solid	

obtained	was	filtered	off	and	recrystallized	from	ethanol	to	give	
21b	as	white	crystals	(Scheme	4).	Yield:	77%.	M.p.:	184‐186	°C.	
FT‐IR	 (KBr,	 cm‐1):	 3052	 (CHarom.),	 2987	 (CHaliph.),	 1742,	 1674	
(2C=O),	 1618‐1531	 (C=N	 and	 C=C),	 1063	 (C‐O‐).	MS	 (EI,	m/z,	
(%)):	508	(M,	1),	509	(1),	242	(1),	230	(1),	92	(4),	91	(100),	61	
(2).	Anal.	 calcd.	 for	C26H24N2O5S2:	C,	 61.39;	H,	4.76;	N,	 5.51;	 S,	
12.61.	Found:	C,	61.40,	H,	4.80;	N,	5.60;	S,	12.70%.		
 	
2.2.18.	2,4‐Dihydrazino‐5,6‐diphenylfuro[2,3‐d]pyrimidine	
(22)	
	

A	mixture	of	21a	(0.01mol,	3.92	g,)	and	hydrazine	hydrate	
(0.02	mol,	1	mL)	in	absolute	ethanol	(20	mL)	was	heated	under	
reflux	 for	 40	 h.	 The	 solid	 obtained	 was	 filtered	 off	 and	
recrystallized	 from	 ethanol	 to	 give	 22	 as	 white	 crystals	
(Scheme	 4).	 Yield:	 74%.	 M.p.:	 185‐187	 °C.	 FT‐IR	 (KBr,	 cm‐1):	
3469‐3125	 (2NH,	 2NH2),	 3054	 (CHarom.),	 1579‐1521	 (C=N	and	
C=C),	1056	(C‐O‐).	MS	(EI,	m/z,	(%)):	318	(M‐N,	16),	152	(24),	
145	(24),	77	(92),	62	(32),	51	(100).	Anal.	calcd.	for	C18H16N6O:	
C,	65.05;	H,	4.85;	N,	25.29. Found:	C,	65.10;	H,	4.90;	N,	25.20%.	
		
2.2.19.	10,11‐Diphenylfuro[2`,3`:4,5]pyrimido[1,6‐d:3,2‐d]‐
1,2,3,4‐bistetrazole	(23)	
	

A	mixture	of	22	(0.01	mol,	3.32	g)	and	sodium	nitrite	(0.01	
mol,	0.69	g)	 in	glacial	acetic	acid	(20	mL)	was	stirred	at	room	
temperature	for	4	h.	The	solid	product	so	formed	was	collected	
and	recrystallized	from	ethanol	to	give	compound	23	as	brown	
crystals	(Scheme	4).	Yield:	78%.	M.p.:	118‐120	°C.	FT‐IR	(KBr,	
cm‐1):	 3055	 (CHarom.),	 1529‐1494	 (C=N	and	C=C),	1054	 (C‐O‐).	
MS	(EI,	m/z,	(%)):	354	(M,	1),	355	(1),	326	(1),	298	(1),	277	(1),	
200	(4),	154	(1),	77	(100).	Anal.	calcd.	for	C18H10N8O:	C,	61.02;	
H,	2.84;	N,	31.62. Found:	C,	61.10;	H,	2.90;	N,	31.60%.	
	
3.	Results	and	discussion	 
	
3.1.	Synthesis	
		

It	 has	 been	 reported	 that,	 the	 reaction	 of	 heterocyclic	 o‐
aminonitriles	 with	 carbon	 disulphide	 in	 basic	 medium	 gives	
fused	 pyrimidinethione	 [18].	 Thus,	 when	 compound	 1	 was	
allowed	 to	 react	 with	 CS2	 in	 alcoholic	 KOH	 solution,	 5,6‐
diphenylfuro[2,3‐d]	 pyrimidine‐2,4(1H,3H)‐dithione	 (2)	 was	
obtained.	 IR	spectrum	of	compound	2	revealed	the	absence	of	
C≡N	function	at	2200	cm‐1	and	displayed	two	absorption	bands	
attributed	 to	 2	 C=S	 at	 1243	 and	 1206	 cm‐1	 and	 its	 mass	
spectrometry	 showed	 a	 molecular	 ion	 peak	 at	m/z	 336	 (M+,	
88%).	 Compound	2	 is	 considered	 as	 a	 convinent	 synthon	 for	
the	 synthesis	 of	 some	 novel	 pyrazolylfuropyrimidinethiones.	
Thus,	 the	 interaction	 of	 hydrazino	 compound	 3	 with	 some	
interesting	 enaminones	 like	 1‐dimethylamino‐2,3‐diphenyl‐
propen‐3‐one	 (4)	 in	 absolute	 ethanol	 containing	 few	drops	of	
triethylamine	led	to	formation	of	4‐(4,5‐diphenylpyrazol‐1‐yl)‐



278	 Abdel‐Hamid	et	al.	/	European	Journal	of	Chemistry	3	(3)	(2012)	273‐278	
	
5,6‐diphenylfuro[2,3‐d]pyrimidine‐2(1H)‐thione	(5).	While,	the	
reaction	of	compound	3	with	4‐methylidenedimethyl‐amino‐2‐
phenyl‐1,3‐oxazol‐5‐one	 (6)	 [19],	 involved	 ring	 opening	 of	
oxazolone	 ring	 and	 afforded	 4‐(4‐benzoylaminopyrazol‐1‐yl)‐
5,6‐diphenylfuro[2,3‐d]pyrimidine‐2(1H)‐thione	(7).	Moreover,	
polynuclear	 heterocyclic	 systems	 having	 pyrazolylfuro‐
pyrimidinethiones	9	and	11	were	synthesized	by	treatment	of	
compound	 3	 with	 4‐methylidenedimethylamino‐3‐methyl‐1‐
phenylpyrazol‐5‐one	 (8)	 [20],	 and	 3‐methylidenedimethyl‐
aminoindol‐2(1H)‐one	 (10)	 [21],	 respectively	 in	 absolute	
ethanol	 containing	 catalytic	 amount	 of	 triethylamine	 (Scheme	
1).	

On	 the	 other	 hand,	 pyrazolylfuropyrimidinethione	
derivatives	were	prepared	 from	 the	 reaction	of	 the	hydrazino	
compound	 3	 with	 1,3‐dicarbonyl	 compounds.	 Therefore,	
compound	3	 reacted	with	diethyl	malonate,	ethyl	acetoacetate	
and	 acetylacetone	 in	 absolute	 ethanol	 containing	 catalytic	
amount	of	triethylamine	giving	pyrazolylfuropyrimidinethiones	
(12‐14).	The	structures	of	compounds	12‐14	were	established	
from	 their	 correct	 elemental	 analyses	 and	 spectroscopic	 data.	
Whereas,	 the	 4‐[5‐amino‐4‐carboxamido‐3‐(4‐chlorophenyl)‐
2,3‐dihydropyrazol‐1‐yl]‐5,6‐Diphenylfuro[2,3‐d]pyrimidine‐
2(1H)‐thione	 (15)	 was	 obtained	 from	 the	 reaction	 of	
compound	 3	 with	 p‐chlorobenzylidenecyanoacetamide	 under	
the	same	reaction	conditions	(Scheme	2).	

Also,	 one	 of	 our	 targets	 was	 the	 use	 of	 compound	 3	 to	
synthesize	some	new	furotriazolopyrimidinethiones.	Thus,	 the	
reaction	 of	 compound	 3	 with	 benzoyl	 chloride	 in	 boiling	
pyridine	 yielded	 3,8,9‐triphenylfuro[2`,3`:4,5]pyrimido[6,1‐c]‐
1,2,4‐triazole‐5(6H)‐thione	 (16).	 Formation	 of	 16	 involves	
benzoylation	 followed	 by	 cyclocondensation	 process.	
Condensation	 of	 compound	3	with	p‐chlorobenzaldehyde	 and	
acetophenone	 in	 boiling	 glacial	 acetic	 acid	 afforded	 the	
arylidenehydrazono	 intermediate,	 which	 underwent	 cyclo‐
addition	 reaction	 to	 give	 3‐(4‐chlorophenyl)‐2,3‐dihydro‐8,9‐
diphenyl‐furo[2`,3`:4,5]pyrimido[6,1‐c]‐1,2,4‐triazole‐5(6H)‐
thione	 (17)	 and	 3‐methyl‐3,8,9‐triphenylfuro[2`,3`:4,5]	
pyrimido[6,1‐c]‐1,2,4‐triazole‐5(6H)‐thione	 (18),	 respectively.	
Also,	 the	 effect	 of	 carbon	 disulphide	 in	 alcoholic	 potassium	
hydroxide	 and	 nitrous	 acid	 on	 compound	 3	was	 studied	 and	
yielded	furotriazolopyrimidinedithione	(19)	and	furotetrazolo‐
pyrimidinethione	 (20),	 respectively	 (Scheme	 3).	 Compounds	
16‐20	were	established	on	the	basis	of	their	elemental	analysis	
and	spectral	data	(see	experimental	section).	

Furthermore,	alkylation	of	compound	2	with	ethyl	iodide	in	
DMF/KOH	 mixture	 and	 ethyl	 chloroacetate	 in	 boiling	 DMF	
yielded	 2,4‐dialkylthio	 derivatives	 21a,	 b,	 respectively.	
Treatment	 of	 21a	with	 hydrazine	 hydrate	 in	 boiling	 ethanol	
afforded	 2,4‐dihydrazino‐5,6‐diphenylfuro[2,3‐d]pyrimidine	
(22),	 which	 on	 reacting	 with	 nitrous	 acid	 at	 0	 oC	 gave	 the	
ditetrazolofuropyrimidine,	23	(Scheme	4).	
	
4.	Conclusion	
	

In	conclusion,	we	have	presented	various	methods	 for	 the	
synthesis	 of	 new	 heteroarylfuro[2,3‐d]pyrimidines	 such	 as	
pyrazolylfuropyrimidinethiones	and	condensed	furopyrimidine	
derivatives	 such	 as	 furotriazolopyrimidinethiones	 and	 bis	
tetrazolofuropyrimidine	 starting	 from	 2‐amino‐4,5‐
diphenylfuran‐3‐carbonitrile.	

	
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