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European	Journal	of	Chemistry	5	(2)	(2014)	277‐286	

	

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.5.2.277‐286.976	

	
	

	

	

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

	 	 	

Friedel‐Crafts	chemistry:	Part	41.	A	new	facile	synthesis	of	indeno[1,2‐c]	
pyrazoles,	2H‐benzo[g]indazoles	and	benzo[6,7]cyclohepta[1,2‐c]pyrazoles	via	
Friedel‐Crafts	ring	closures	

Hassan	Abdou	Kotb	Abd	El‐Aal	*,	Ahmed	Mahmoud	Abdel	Mageed	El‐Khawaga	and	Ali	Ali	Khalaf	

Chemistry	Department,	Faculty	of	Science,	Assiut	University,	Assiut,	71516,	Egypt	

*Corresponding	author	at:	Chemistry	Department,	Faculty	of	Science,	Assiut	University,	Assiut,	71516,	Egypt.		
Tel.:	+2.088.2411485.	Fax:	+2.088.2342708.	E‐mail	address:	hassankotb33@yahoo.com	(H.A.K.A.	El‐Aal).	

	
	

	 	

	 	 	
ARTICLE	INFORMATION	 	 ABSTRACT	

	
DOI:	10.5155/eurjchem.5.2.277‐286.976	

Received:	17	November	2013	
Received	in	revised	form:	25	December	2013	
Accepted:	25	December	2013	
Online:	30	June	2014	

KEYWORDS	

	 Expedient	and	novel	alternative	synthesis	of	some	fused	heteropolycycles	containing	pyrazole
moiety	is	described.	A	series	of	indeno[1,2‐c]pyrazoles,	2H‐benzo[g]indazoles	and	benzo[6,7]
cyclohepta[1,2‐c]pyrazoles	 were	 prepared	 by	 Friedel‐Crafts	 ring	 closure	 of	 suitable
synthesized	 carboxylic	 acids	 and	 alkanols	 in	 the	 presence	 of	 AlCl3/CH3NO2	 or	 P2O5	 or	 PPA
(polyphosphoric	 acid)	 catalysts.	 The	 precursor	 acids	 were	 obtained	 by	 utilizing	 KMnO4

oxidation	 of	 the	 corresponding	 aldehyde,	 alkylations	 of	 diethyl	 malonates	 and	 Perkin	 type
approaches,	whereas	starting	alkanols	were	smoothly	obtained	by	reaction	of	carboxylic	acid
ester	with	Grignard	reagent.	To	exemplify,	cyclizations	of	5‐chloro‐1,3‐diphenyl‐1H‐pyrazole‐
4‐carboxylic	 acid	 (6)	 were	 accomplished	 using	 the	 above	 catalysts	 afforded	 3‐chloro‐2‐
phenylindeno[1,2‐c]pyrazol‐4(2H)‐one	 (1b).	 Similarly,	 cyclization	 of	 the	 2‐(5‐chloro‐1,3‐
diphenyl‐1H‐pyrazol‐4‐yl)propan‐2‐ol	 (8)	 by	 a	 Friedel–Crafts‐type	 ring	 closure	 afforded	 the
3‐chloro‐2,4‐dihydro‐4,4‐dimethyl‐2‐phenylindeno[1,2‐c]pyrazole	(1a).	

Benzo[g]indazole	
Heteropolycycles		
Heteroarylalkanols	
Indeno[1,2‐c]pyrazole		
Friedel‐Crafts	ring	closures	
Benzo[6,7]cyclohepta[1,2‐c]pyrazole	

	
1.	Introduction	
	

The	 synthesis	 of	 pyrazoles	 and	 their	 condensed	 scaffolds	
have	been	a	subject	of	consistent	interest	because	of	their	long	
history	of	application	in	pharmaceutical	[1‐3]	and	agrochemical	
[4‐6]	industries.		

Over	the	past	two	decades,	pyrazole‐containing	compounds	
have	 received	 considerable	 attention	 owing	 to	 their	 diverse	
chemotherapeutic	potentials.	They	display	a	broad	spectrum	of	
biological	 activities	 such	 as	 antimicrobial	 [7],	 antifungal	 [8],	
anti‐inflammatory	[9],	antitumor	[10],	antihyperglycemic	[11],	
analgesic	 [12],	 antipyretic	 [13],	 antibacterial	 [14],	 sedative‐
hypnotic	 [15],	 antidepressant	 [16],	 anti‐rheumatoid	 arthritis	
[17],	anticonvulsant	[18],	antipsychotic	[19],	antileukemic	[20]	
and	 as	 HIV	 integrase	 inhibitor	 [21]	 agents.	 Also	 pyrazole	
derivatives	 were	 present	 in	 numerous	 herbicides	 [22],	
fungicides	[23],	insecticides	[24],	pesticides	[25]	and	dyestuffs	
[26].	 In	 spite	 of	 they	 are	 rare	 in	 nature,	 the	 only	 natural	
pyrazole	 (1‐pyrazolyl‐alanine)	 was	 isolated	 from	 seeds	 of	
watermelons	[27].	

Although	 the	 discovery	 [28]	 of	 pyrazoles	 as	 antipyretic	
agents	dated	back	to	1884,	synthesis	of	pyrazole	systems	have	
been	a	prominent	 research	objective	 for	over	a	 century	and	a	
variety	 of	 well‐established	 synthetic	 methodologies	 are	

available	 in	 the	 literature.	 Of	 the	 methods	 developed,	 1,3‐
dipolar	cycloadditions	of	diazocompounds	 [29]	or	nitrilimines	
with	alkynes	[30]	or	alkenes	[31,32],	reaction	of	chalcones	and	
hydrazines	 [33],	 reaction	 of	 enaminones	 with	 different	
aminoheterocycles	 [34],	 condensation	 of	 1,3‐diketones	 and	
hydrazines	 in	 the	 presence	 of	 an	 acidic	 catalyst	 [35]	 and	
coupling	 of	 terminal	 alkynes	 with	 hydrazine	 and	 carbon	
monoxide	[36].	

Among	 different	 condensed	 pyrazoles	 polycycles,	
indeno[1,2‐c]pyrazole	 (1)	 [37,38],	 2H‐benzo[g]indazole	 (2)	
[39‐41]	 and	 benzo[6,7]cyclohepta[1,2‐c]pyrazole	 (3)	 [42]	
derivatives	 (Figure	 1)	 are	 such	molecules	which	 have	 unique	
nitrogen‐containing	 tricyclic	 structures	 are	 known	 to	 exert	
biological	activities	 in	many	active	pharmaceutical	 ingredients	
[43,44].	

Literature	 survey	 revealed	 that	 limited	 numbers	 of	
strategies	 have	 been	 successfully	 applied	 in	 the	 synthesis	 of	
such	 1‐3	 skeletons	 derivatives.	 However,	 all	 such	 reported	
methods	were	based	on	the	addition	of	substituted	hydrazines	
to	suitable	chalcones,	β‐diketones	and	α‐keto‐β‐hydroxyesters.		

In	an	alternative	pioneering	strategy,	Li	et	al.	[45]	achieved	
the	 synthesis	 of	 scaffold	 2	 and	 variety	 of	 aza‐polycyclic	
aromatic	 compounds	 via	 superelectrophilic	 cyclizations	 of	
alkenyl‐substituted	N‐heterocycles	with	triflic	acid	(CF3SO3H).		

 



278	 El‐Aal	et	al.	/	European	Journal	of	Chemistry	5	(2)	(2014)	277‐286	
	

 

 
	

Figure	1.	Pyrazole	heteropolycycles	containing	pharmaceuticals.	
	
	
The	search	for	new	methods	for	the	simple,	direct,	concise,	

atom‐economical	 synthetic	 route	 and	 efficient	 construction	 of	
this	 class	 of	 pyrazole	 compounds	 still	 constitutes	 a	 major	
challenge	in	organic	synthesis.		

In	 recent	communications	 [46‐50],	we	have	demonstrated	
simple	alternative	procedures	in	the	construction	of	novel	and	
known	 heterocyclic	 systems	 proving	 the	 synthetic	 utility	 of	
Friedel‐Crafts	 [51‐54]	 cyclialkylation	 approach.	 The	 results	
manifested	that	a	number	of	difficult	heterocyclic	skeletons	can	
be	easily	prepared	with	 the	advantages	of	 short	 reaction	 time	
and	high	yield.	In	view	of	the	above	reports	and	in	continuation	
of	our	research	in	Friedel‐Crafts	ring	closures,	herein,	we	wish	
to	 report	 facile	 and	 efficient	 synthesis	 of	 substituted	
indeno[1,2‐c]pyrazoles,	 2H‐benzo[g]indazoles	 and	 benzo[6,7]	
cyclohepta[1,2‐c]pyrazole	 via	 Friedel‐Crafts	 ring	 closures	 of	
heteoraryl	acids	and	alkanols	in	the	presence	of	both	Brönsted	
and	Lewis	acid	catalysts.	
	
2.	Experimental	
	
2.1.	Instrumentation	
	

All	reagents	were	purchased	from	Merck,	Sigma	or	Aldrich	
Chemical	 Co.	 and	 were	 used	 without	 further	 purification.	
Melting	 points	 were	 measured	 on	 a	 digital	 Gallenkamp	
capillary	melting	point	apparatus	and	are	uncorrected.	The	 IR	
spectra	 were	 determined	 with	 a	 Shimadzu	 470	 infrared	
spectrophotometer	 using	 KBr	wafer	 and	 thin	 film	 techniques.	
The	1H	and	13C	NMR	spectra	were	recorded	on	Jeol	LA	400	MHz	
FT‐NMR	(400	MHz	for	1H,	100	MHz	for	13C)	and	on	Varian	NMR	
(90	MHz)	spectrometers	using	CDCl3	or	DMSO‐d6	solvents	with	
TMS	as	 internal	 standard.	Chemical	 shifts	 (δ)	and	 J	 values	are	
reported	in	ppm	and	Hz,	respectively.	Elemental	analyses	were	
performed	on	a	Perkin‐Elmer	2400	Series	II	analyser.	The	mass	
spectra	were	 recorded	on	a	 JEOL	 JMS	600	spectrometer	at	an	
ionizing	potential	of	70	eV	(EI)	electron	impact	ionization	mode	
using	 the	 direct	 inlet	 system.	 Reactions	 were	 monitored	 by	
thin‐layer	chromatography	(TLC)	using	pre‐coated	silica	plates	
and	 visualized	 with	 UV	 light.	 Flash	 column	 chromatography	
was	performed	on	silica	gel	and	basic	alumina.	
	
2.2.	Synthesis	
	
2.2.1.	5‐Chloro‐1,3‐diphenyl‐1H‐pyrazole‐4‐carbaldehyde	(5)	
	

Pyrazolone	4	(4.7	g,	0.02	mol)	was	added	in	small	portions	
over	5	min	to	an	ice‐cold	Vilsmeier	reagent	prepared	by	slowly	
addition	of	POCl3	 (9.8	mL,	16.12	g,	0.1	mol)	 to	DMF	(17.8	mL,	
16.8	g,	0.23	mol)	at	0	°C	over	30	min.	The	reaction	mixture	was	
heated	for	3	h	at	90	°C	then	cooled	to	0	°C,	poured	into	ice‐cold	
water	 (100	mL)	 and	 finally	 treated	with	potassium	 carbonate	
till	 pH	=	9.	The	separated	yellow	solid	was	 filtered,	dried	and	
recrystallized	 from	 benzene	 to	 afford	 (4.4	 g,	 79	 %)	 of	 pure	
aldehyde	5	(Scheme	1).	Color:	White	crystals.	M.p.:	107	°C	(Lit.	
[55],	 M.p.:	 109‐111	 C).	 IR	 (KBr,	 ν,	 cm‐1):	 3110,	 3065	 (CH)	
(Aromatic),	 2830,	 2745	 (CH)	 (aldehyde),	 1695	 (C=O)	
(aldehyde),	 1605,	 1590,	 1489,	 1440	 (C=C)	 (Aromatic),	 1360,	

1189,	716,	658.	1H	NMR	(90	MHz,	CDCl3,	δ,	ppm):	7.20‐8.90	(m,	
10	H,	Ar‐H),	10.30	(s,	1H,	CHO).	MS	(EI,	m/z	(%)):	283	(M++1,	
45),	 284	 (M++2,	 28),	 282	 (M+,	 100),	 254	 (16),	 253	 (25),	 248	
(15),	220	(18),	77	(86),	51	(92).	Anal.	calcd.	for	C16H11ClN2O:	C,	
67.96;	H,	3.92;	N,	9.91.	Found:	C,	68.25;	H,	3.77;	N,	9.90%.	
	
2.2.2.	5‐Chloro‐1,3‐diphenyl‐1H‐pyrazole‐4‐carboxylic	acid	
(6)	
	

To	a	solution	of	compound	5	(4.2	g,	15	mmol)	in	a	mixture	
of	H2O/t‐butanol	(1:1,	30	mL)	was	added	a	solution	of	KMnO4	
(3.3	g,	21	mmol)	in	H2O	(30	mL)	at	70‐80	°C	over	2	h.	Then	an	
aqueous	 solution	 of	 KOH	 (10%,	 30	 mL)	 was	 added	 while	
stirring	 until	 the	 solution	 turned	 alkaline.	 The	 mixture	 was	
filtered	 and	 the	 clear	 filtrate	 was	 acidified	with	 concentrated	
hydrochloric	 acid	 (20	 mL,	 30%)	 to	 pH	 =	 2.	 The	 resulting	
precipitate	 was	 filtered,	 washed	 with	 water,	 dried	 and	
crystallized	 from	 ethanol	 to	 give	 (3.8	 g,	 85	%)	 of	 pure	 acid	6	
(Scheme	1).	Color:	White	crystals.	M.p.:	183	°C.	IR	(KBr,	ν,	cm‐1):	
3440	 (OH)	 (acid),	 3105	 (CH)	 (Aromatic),	 1690(C=O)	 (acid),	
1610,	1585,	1473,	1440	(C=C)	(Aromatic),	1360,	1140,	755.	1H	
NMR	 (90	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.60‐8.70	 (m,	 10H,	 Ar‐H),	
11.20	(s,	1H,	COOH).	Anal.	calcd.	 for	C16H11ClN2O2:	C,	64.33;	H,	
3.71;	N,	9.38.	Found;	C,	64.52;	H,	3.72;	N,	9.33%.	
	
2.2.3.	4‐Bromo‐1,3‐diphenyl‐1H‐pyrazol‐5(4H)‐one	(9)	
	

To	a	an	ice‐cold	solution	of	pyrazolone	4	(4.7	g,	20	mmol)	
in	 AcOH	 (30	mL)	was	 added	 a	 solution	 of	 bromine	 (4.3	 g,	 27	
mmol)	in	AcOH	(10	mL)	over	a	period	of	10	min	at	5‐10	°C.	The	
reaction	 mixture	 was	 stirred	 for	 10	 min,	 diluted	 with	 water	
(100	mL)	 over	 5‐10	min	 and	 left	 to	 stand	 in	 refrigerator	 for	
overnight.	 The	 solid	 was	 filtered,	 washed	 with	 AcOH	 (20	 %)	
and	 dried.	 Crystallization	 from	 ethanol	 gave	 (4.6	 g,	 74	%)	 of	
pure	 bromopyrazolone	 9	 (Scheme	 1).	 Color:	 Pale	 yellow	
needless.	M.p.:	117	°C.	IR	(KBr,	ν,	cm‐1):	3090	(CH)	(Aromatic),	
2970	(CH)	 (pyrazole),	1678	(C=O)	(amide),	1593,	1560,	1490,	
1455	(C=C)	(Aromatic),	1340,	1170,	745,	670.	1H	NMR	(90	MHz,	
CDCl3,	δ,	ppm):	4.6	(s,	1H,	CH),	7.45‐8.50	(m,	10H,	Ar‐H).	Anal.	
calcd.	 for	 C15H11BrN2O:	 C,	 57.16;	 H,	 3.52;	 N,	 8.89.	 Found;	 C,	
57.05;	H,	3.55;	N,	8.84%.	
	
2.2.4.	General	procedure	for	the	synthesis	of	substituted	
acids	10a,b	
	

A	 solution	 of	 4‐bromo‐1,3‐diphenyl‐1H‐pyrazol‐5(4H)‐one	
(9)	 (4.7	 g,	 15	 mmol)	 in	 30	 mL	 of	 dry	 benzene	 was	 added	
dropwise	over	40	minutes	 to	an	 ice‐cold	suspension	of	sodio‐
malonic	 ester	 prepared	 from	 sodium	 (1.0	 g,	 45	 mmol)	 and	
substituted	 diethyl	 malonate	 (5.3	 g,	 33	 mmol)	 in	 30	 mL	 of	
absolute	ethanol.	After	complete	addition,	the	reaction	mixture	
was	 kept	 in	 a	 refrigerator	 for	 24	h	 and	 then	 refluxed	 for	 4	 h.	
The	 solvents	 were	 evaporated	 and	 the	 resulting	 ester	 was	
refluxed	for	2h	with	KOH	solution	(25	mL,	30	%).	The	mixture	
was	diluted	with	water	(30	mL),	refluxed	for	an	additional	1	h,	
cooled	 and	 acidified	 with	 HCl	 solution	 (40	 mL,	 30	 %).	 The	
crude	substituted	malonic	acid	was	filtered,	washed	with	water	
and	dried.		



El‐Aal	et	al.	/	European	Journal	of	Chemistry	5	(2)	(2014)	277‐286	 279	
 

	

	
	

Reagents	and	conditions:	(i)	POCl3/DMF,	90	°C,	3	h,	K2CO3,	(ii)	KMnO4,	H2O/t‐butanol,	70‐80	°C,	2	h,	(iii)	EtOH/H2SO4,	8h,	reflux,	Na2CO3,	(iv)	MeMgI,	THF/Et2O,	rt,	
NH4Cl	soln	(Table	1),	(v)	Br2/AcOH,	5‐10	°C,	20	min,	(vi)	(a)	NaCH(COOEt)2,	KOH,	24	h,	(b)	heated	at	190‐200	°C.	

	
Scheme	1	

	
	
The	acid	was	then	heated	at	190‐200	°C	in	an	oil	bath	with	

stirring	for	20	minutes	and	the	melt	was	poured	into	20	ml	of	
acetone.	 The	 acetone	 solution	 was	 treated	 with	 charcoal,	
warmed,	 filtered	 and	 the	 solvent	 was	 evaporated	 to	 afford	
crude	 acids.	 Crystallization	 from	 suitable	 solvents	 gave	 pure	
acids	10a,b	(Scheme	1).	Analytical,	physical	and	spectroscopic	
data	are	given	in	the	following:	

2‐(4,5‐Dihydro‐5‐oxo‐1,3‐diphenyl‐1H‐pyrazol‐4‐yl)acetic	
acid	(10a):	Color:	Pale	yellow	crystals.	Yield:	82%.	M.p.:	124	°C	
(benzene).	 IR	 (KBr,	 ν,	 cm‐1):	 3370	 (OH)	 (acid),	 3085	 (CH)	
(Aromatic),	 2950	 (CH)	 (alkyl),	 1720	 (C=O)	 (acid),	 1674	 (C=O)	
(amide),	1610,	1590,	1460,	1445	(C=C)	(Aromatic),	1335,	1180,	
745.	1H	NMR	(90	MHz,	CDCl3,	δ,	ppm):	2.61	(t,	1Ha,	J	=	14.2	Hz,	
CH2),	2.75	(t,	1Hb,	J	=	14.2	Hz,	CH2),	2.82	(app.	t,	1H,	J	=	10.4	Hz,	
CH),	7.30‐8.55	(m,	10H,	Ar‐H),	10.9	(s,	1H,	COOH).	Anal.	calcd.	
for	 C17H14N2O3:	 C,	 69.38;	 H,	 4.79;	 N,	 9.52.	 Found;	 C,	 69.25;	 H,	
4.56;	N,	9.50%.	

2‐(4,5‐Dihydro‐5‐oxo‐1,3‐diphenyl‐1H‐pyrazol‐4‐yl) 	
propanoic	acid	 (10b):	 Color:	White	 crystals.	 Yield:	 75%.	M.p.:	
95	°C	(ethanol).	IR	(KBr,	ν,	cm‐1):	3355	(OH)	(acid),	3075	(CH)	
(Aromatic),	 2977(CH)	 (alkyl),	 1715	 (C=O)	 (acid),	 1664	 (C=O)	
(amide),	1600,	1585,	1450,	1440,	1380,	1130,	749.	1H	NMR	(90	
MHz,	CDCl3,	δ,	ppm):	1.24	(d,	3H,	J	=	9.4	Hz,	CH3),	2.92	(p,	1H,	J	=	
12.4	Hz,	CH),	3.04	(app.	q,	1H,	J	=	12.4	Hz,	CH),	7.35‐8.23	(m,	10	
H,	 Ar‐H),	 11.6	 (s,	 1H,	 COOH).	 Anal.	 calcd.	 for	 C18H16N2O3:	 C,	
70.12;	H,	5.23;	N,	9.09.	Found;	C,	70.05;	H,	5.22;	N,	9.26%.	
	
2.2.5.	General	procedure	for	the	synthesis	of	acids	13a,b	
	

A	mixture	of	 aldehyde	5	 (4.2	 g,	 15	mmol),	 acid	anhydride	
(18	 mmol)	 and	 sodium	 salt	 of	 the	 corresponding	 acid	 (18	
mmol)	 was	 heated	 in	 an	 oil	 bath	 at	 140‐150	 °C	 with	
occasionally	 stirring	 for	 10‐12	 h.	 The	 warm	 mixture	 was	
poured	with	stirring	 into	water	(50	mL),	basified	with	Na2CO3	

solution	 (20	mL,	30%)	and	extracted	with	ether	 (2	×	20	mL).	
The	 ether	 extracts	 was	 discarded	 and	 the	 resulting	 solution	
was	 heated	with	 decolorizing	 carbon	 (1	 g),	 filtered	while	 hot	
then	 it	 was	 poured	 with	 stirring	 into	 ice‐cold	 concentrated	
hydrochloric	acid	chopped	with	ice	(50	mL).	After	standing	for	
overnight,	the	precipitated	acids	13a	or	b	was	filtered,	washed	
successively	 with	 water	 and	 left	 to	 dry	 (Scheme	 2).	
Purifications,	 yields	 and	 spectral	 data	 are	 given	 in	 the	
following:	

	(E)‐3‐(5‐Chloro‐1,3‐diphenyl‐1H‐pyrazol‐4‐yl)acrylic	acid	
(13a):	Color:	White	crystals.	Yield:	74%.	M.p.:	156	°C	(acetone).	
IR	 (KBr,	 ν,	 cm‐1):	 3410	 (OH)	 (br,	 acid),	 3105	 (=CH)	 (Alkene),	
3060	 (CH)	 (Aromatic),	 2995	 (CH)	 (alkyl),	 1697	 (C=O)	 (acid),	
1600	(C=C)	(Alkene),	1580,	1463,	1440	(C=C)	(Aromatic),	1360,	
1140,	745.	1H	NMR	(90	MHz,	DMSO‐d6,	δ,	ppm):	6.35	(d,	1H,	J	=	
16.4	Hz,	=CH),	7.20‐8.10	 (m,	10	H,	Ar‐H),	8.31	(d,	1H,	 J	=	16.4	
Hz,	 =CH),	 11.2	 (s,	 1H,	 COOH).	 Anal.	 calcd.	 for	 C18H13ClN2O2:	 C,	
66.57;	H,	4.03;	N,	8.62.	Found;	C,	66.49;	H,	4.22;	N,	8.64%.	

(E)‐3‐(5‐Chloro‐1,3‐diphenyl‐1H‐pyrazol‐4‐yl)‐2‐methyl	
acrylic	 acid	 (13b):	 Color:	 Pale	 yellow	 solid.	 Yield:	 82%.	 M.p.:	
172	°C	(ethanol).	 IR	(KBr,	ν,	cm‐1):	3410	(OH)	(br,	acid),	3094	
(=CH)	(Alkene),	3024	(CH)	(Aromatic),	2975	(CH)	(alkyl),	1700	
(C=O)	 (acid),	 1622	 (C=C)	 (Alkene),	 1588,	 1450,	 1440	 (C=C)	
(Aromatic),	 1385,	 1145,	 749.	 1H	 NMR	 (90	 MHz,	 DMSO‐d6,	 δ,	
ppm):	 1.83	 (s,	 3H,	 CH3),	 7.20‐8.36	 (11	H,	m,	 Ar‐H,	 =CH),	 10.9	
(1H,	s,	COOH).	Anal.	calcd.	for	C19H15ClN2O2:	C,	67.36;	H,	4.46;	N,	
8.27.	Found;	C,	67.30;	H,	4.55;	N,	8.40%.	
	
2.2.6.	General	procedure	for	reduction	of	acids	14a,b	
	

To	 a	 solution	 of	 acid	 13a	 or	 13b	 (10	 mmol)	 in	 sodium	
hydroxide	 solution	 (15	 mL,	 1	 N)	 was	 treated	 with	 sodium	
amalgam	(25	g,	2.5%)	in	small	portions	over	a	period	of	20	min	
with	vigorous	stirring.		



280	 El‐Aal	et	al.	/	European	Journal	of	Chemistry	5	(2)	(2014)	277‐286	
	

	

 
	

Reagents	and	conditions:	(i)	(Ac2O/AcONa)	or	(Pr2O/PrONa)/140‐150	°C,	Na2CO3,	10‐12	h,	(ii)	Na/Hg	(2.5	%),	NaOH,	5	h,	(iii)	EtOH/H2SO4,	8	h,	reflux,	
Na2CO3,	(iv)	MeMgI,	THF/Et2O,	rt,	NH4Cl	solution	(Table	1).	

Scheme	2	
	
	
The	reaction	mixture	was	stirred	for	additional	5	h	at	room	

temperature	 and	 then	 mercury	 was	 separated,	 washed	 with	
water	and	the	washings	were	added	to	the	main	solution.	The	
whole	 solution	 was	 acidified	 with	 concentrated	 HCl	 (10	 mL)	
and	 the	 crude	 acid	14a	or	b	was	 filtered,	washed	with	water	
and	dried	(Scheme	2).	Yields	and	spectral	data	are	given	in	the	
following:	

3‐(5‐Chloro‐1,3‐diphenyl‐1H‐pyrazol‐4‐yl)propanoic	 acid	
(14a):	Color:	White	needles.	Yield:	92%.	M.p.:	135	°C	(ethanol).	
IR	 (KBr,	 ν,	 cm‐1):	 3345	 (OH)	 (br,	 acid),	 3090(CH)	 (Aromatic),	
2988(CH)	 (alkyl),	 2490,	1720	 (C=O)	 (acid),	1605,	1590,	1465,	
1450(C=C)	 (Aromatic),	 1350,	 1165,	 745.	 1H	 NMR	 (90	 MHz,	
CDCl3,	δ,	ppm):	2.65	(t,	2H,	J	=	6.2	Hz,	CH2),	2.90	(t,	2H,	 J	=	6.2	
Hz,	 CH2),	 6.83‐8.15	 (10	H,	m,	Ar‐H),	 10.5	 (1H,	 s,	 COOH).	Anal.	
calcd.	 for	 C18H15ClN2O2:	 C,	 66.16;	 H,	 4.63;	 N,	 8.57.	 Found;	 C,	
66.24;	H,	4.64;	N,	8.53%.	

2‐((5‐Chloro‐1,3‐diphenyl‐1H‐pyrazol‐4‐yl)methyl)propanoic	
acid	 (14b):	 Color:	 Pale	 yellow	 solid.	 Yield:	 86%.	 M.p.:	 94	 °C	
(ethanol).	 IR	 (KBr,	 ν,	 cm‐1):	 3320	 (OH)	 (br,	 acid),	 3030	 (CH)	
(Aromatic),	2975	 (CH)	 (alkyl),	1715	 (C=O)	 (acid),	1600,	1580,	
1450	 (C=C)	 (Aromatic),	 1350,	 1140,	 755.	 1H	 NMR	 (90	 MHz,	
CDCl3,	δ,	ppm):	1.10	(d,	3H,	J	=	10.4	Hz,	CH3),	2.63	(t,	Ha,	J	=	16.3	
Hz,	CH2),	2.73	(ddq,	1H,	J	=	9.3	Hz,	‐CH),	2.86	(dd,	Hb,	J	=	16.3	
Hz,	 CH2),	 6.90‐8.25	 (m,	 10	H,	Ar‐H),	 10.8	 (s,	 1H,	 COOH).	Anal.	
calcd.	 for	 C19H17ClN2O2:	 C,	 66.96;	 H,	 5.03;	 N,	 8.22.	 Found;	 C,	
66.95;	H,	4.85;	N,	8.37%.	
	
2.2.7.	General	procedure	for	the	synthesis	of	ester	7	or	11a,b	
or	15a,b	
	

A	mixture	of	acid	6	or	10a,b	or	14a,b	(15	mmol),	absolute	
ethanol	 (30	 mL)	 and	 concentrated	 sulfuric	 acid	 (4	 mL)	 was	
refluxed	for	8	h.	The	excess	alcohol	was	removed	in	vacuo	and	
the	resulting	residue	was	poured	into	water	(100	mL),	basified	
by	 addition	 of	 solid	 Na2CO3	 and	 left	 to	 stand	 for	 3	 h	 at	
refrigerator.	The	product	was	filtered,	washed	with	water	and	
dried	to	yield	the	crude	esters.	These	products	were	subjected	
to	 flash	 column	 chromatography	 (basic	 alumina,	 EtOAc/n‐
hexane,	 2/1)	 to	 give	 the	 pure	 esters	 7	 or	 11a,b	 or	 15a,b	
(Scheme	2).	Yields,	 further	purifications	and	spectral	data	 are	
given	in	the	following:	

Ethyl	 5‐chloro‐1,3‐diphenyl‐1H‐pyrazole‐4‐carboxylate	 (7):	
Color:	Pale	yellow	crystals.	Yield:	90%.	M.p.:	105	°C	(benzene).	
IR	 (KBr,	 ν,	 cm‐1):	 3070	 (CH)	 (Aromatic),	 2965	 (CH)	 (alkyl),	

1715	(C=O)	(ester),	1600,	1585,	1490,	1440	(C=C)	(Aromatic),	
1340,	1230,	750.	1H	NMR	(90	MHz,	CDCl3,	δ,	ppm):	1.27	(t,	3H,	J	
=	7.5	Hz,	CH3),	4.40	(q,	2H,	J	=	7.5	Hz,	CH2),	7.40‐8.60	(m,	10H,	
Ar‐H).	Anal.	 calcd.	 for	C18H15ClN2O2:	C,	 66.16;	H,	4.63;	N,	8.57.	
Found;	C,	66.27;	H,	4.36;	N,	8.56%.	

Ethyl	 2‐(4,5‐dihydro‐5‐oxo‐1,3‐diphenyl‐1H‐pyrazol‐4‐yl)	
acetate	 (11a):	 Color:	 White	 plates.	 Yield:	 88	%.	 M.p.:	 142	 °C	
(ethanol).	 IR	 (KBr,	 ν,	 cm‐1):	 3083	 (CH)	 (Aromatic),	 2980	 (CH)	
(alkyl),	 1745	 (C=O)	 (ester),	 1682	 (C=O)	 (amide),	 1605,	 1585,	
1460,	 1455	 (C=C)	 (Aromatic),	 1330,	 1275,	 745.	 1H	 NMR	 (90	
MHz,	CDCl3,	δ,	ppm):	1.32	(t,	3H,	J	=	7.5	Hz,	CH3),	2.62	(dd,	1Ha,	J	
=	14.2	Hz,	CH2),	2.74	(t,	1Hb,	J	=	14.2	Hz,	CH2),	3.27	(t,	1H,	 J	=	
10.4	Hz,	CH),	4.22	(q,	2H,	 J	=	7.5	Hz,	CH2),	7.50‐8.30	(m,	10	H,	
Ar‐H).	 Anal.	 calcd.	 for	 C19H18N2O3:	 C,	 70.79;	 H,	 5.63;	 N,	 8.69.	
Found;	C,	70.83;	H,	5.74;	N,	8.49%.	

Ethyl	 2‐(4,5‐dihydro‐5‐oxo‐1,3‐diphenyl‐1H‐pyrazol‐4‐yl)	
propanoate	(11b):	Color:	Reddish	viscous	oil.	Yield:	89	%.	nD25	=	
1.644.	 IR	 (Film,	 ν,	 cm‐1):	 3075	 (CH)	 (Aromatic),	 2977	 (CH)	
(alkyl),	 1740	 (C=O)	 (ester),	 1673	 (C=O)	 (amide),	 1600,	 1585,	
1495,	 1455	 (C=C)	 (Aromatic),	 1340,	 1245,	 745.	 1H	 NMR	 (90	
MHz,	CDCl3,	δ,	ppm):	1.15	(d,	3H,	J	=	9.4	Hz,	CH3),	1.35	(t,	3H,	J	=	
7.5	Hz,	CH3),	2.82	(p,	1H,	 J	=	12.5	Hz,	CH),	3.24	(app.	 t,	1H,	 J	=	
12.5	Hz,	CH),	4.20	(q,	2H,	 J	=	7.5	Hz,	CH2),	7.45‐8.50	(m,	10	H,	
Ar‐H).	 Anal.	 calcd.	 for	 C20H20N2O3:	 C,	 71.41;	 H,	 5.99;	 N,	 8.33.	
Found;	C,	71.44;	H,	6.14;	N,	8.09%.	

Ethyl	 3‐(5‐chloro‐1,3‐diphenyl‐1H‐pyrazol‐4‐yl)propanoate	
(15a):	Color:	Yellowish	viscous	oil.	Yield:	85	%.	nD25	=	1.584.	IR	
(Film,	ν,	cm‐1):	3055	(CH)	(Aromatic),	2964	(CH)	(alkyl),	1738	
(C=O)	(ester),	1590,	1550,	1460,	1430	(C=C)	(Aromatic),	1335,	
1265,	750.	1H	NMR	(90	MHz,	CDCl3,	δ,	ppm):	1.30	(t,	3H,	J	=	7.5	
Hz,	CH3),	2.52	(t,	2H,	J	=	6.2	Hz,	CH2),	2.95	(t,	2H,	J	=	6.2	Hz,	CH2),	
4.10	 (q,	 2H,	 J	 =	 7.5	Hz,	 CH2),	 7.22‐8.45	 (m,	 10	H,	 Ar‐H).	 Anal.	
calcd.	 for	 C20H19ClN2O2:	 C,	 67.70;	 H,	 5.40;	 N,	 7.89.	 Found;	 C,	
67.91;	H,	5.37;	N,	7.90%.	

Ethyl	 2‐((5‐chloro‐1,3‐diphenyl‐1H‐pyrazol‐4‐yl)methyl)	
propanoate	(15b):	Color:	Pale	yellow	crystals.	Yield:	86	%.	M.p.:	
74	 °C	(ethanol).	 IR	 (KBr,	ν,	 cm‐1):	3105	(CH)	(Aromatic),	2985	
(CH)	(alkyl),	1742	(C=O)	(ester),	1600,	1560,	1485,	1440	(C=C)	
(Aromatic),	1370,	1220,	747.	1H	NMR	(90	MHz,	CDCl3,	δ,	ppm):	
1.12	(d,	3H,	J	=	10.4	Hz,	CH3),	1.25	(t,	3H,	J	=	7.5	Hz,	CH3),	2.66	
(q,	Ha,	J	=	16.3	Hz,	CH2),	2.71	(ddq,	1H,	J	=	9.3	Hz,	‐CH),	2.94	(dd,	
Hb,	J	=	16.3	Hz,	CH2),	4.25	(q,	2H,	J	=	7.5	Hz,	CH2),	6.95‐8.25	(m,	
10H,	Ar‐H).	Anal.	 calcd.	 for	C21H21ClN2O2:	 C,	 68.38;	H,	 5.74;	N,	
7.59.	Found;	C,	68.36;	H,	5.69;	N,	7.65%.	



El‐Aal	et	al.	/	European	Journal	of	Chemistry	5	(2)	(2014)	277‐286	 281	
 

	
Table	1.	Optimum	conditions	for	the	synthesis	of	heteroarylalkanols	8,	12a,b	and	16a,b.	
Entry	 Substrate	 Product Conditions	a Mp	°C	(nD25) Yield	(%)	b
1	 7	

	

Et2O/THF,	rt,	8	h 92 8	(89)	

2	 11a	

	

Et2O/THF,	rt,	6	h	 (1.597)	 12a	(85)	

3	 11b	

N
N

Ph

Ph

O

OH

12b 	

Et2O/THF,	rt,	8	h 84 12b	(92) 

4	 15a	

	

Et2O,	rt,	4	h 118 16a	(90)

5	 15b	

	

Et2O,	rt,	5	h (1.619) 16b	(86)

a	All	reactions	were	performed	using	0.4	equiv.	excess	of	MeMgI.	
b	Isolated	yield	refer	to	substrate.	
	
	
2.2.8.	General	procedure	for	the	synthesis	of	alcohols	8,	
12a,b,	16a,b	
	

To	an	ice‐cold	Grignard	reagent	solution	obtained	as	usual	
from	Mg	 turnings	 (0.32	 g,	 13	mmol),	 alkyl	 or	 aryl	 halide	 (13	
mmol)	 in	 ether	 (40	mL),	was	 added	 a	 solution	 of	 esters	7	 or	
11a,b	 or	 15a,b	 (4.6	 mmol)	 in	 ether	 or	 THF	 (30	 mL).	 The	
reaction	 mixture	 was	 stirred	 at	 required	 temperature	 for	
appointed	 time	 (Table	 1)	 followed	 by	 decomposition	 with	
saturated	 aqueous	NH4Cl	 solution.	 The	product	was	 extracted	
with	ether	 (3×30	mL)	and	 the	combined	organic	phases	were	
washed	with	water,	dried	over	anhydrous	MgSO4.	The	solvent	
was	 removed	 in	 vacuo	 and	 the	 residue	was	 purified	 by	 flash	
column	 chromatography	 (basic	 alumina,	 EtOAc:n‐hexane,	 3:1,	
v:v)	 resulting	 pure	 alcohols	8	 or	12a,b	 or	16a,b	 (Scheme	 2).	
The	 conditions	 and	 isolated	 yields	 are	 shown	 in	 Table	 1	 and	
spectral	data	are	given	in	the	following:	

2‐(5‐Chloro‐1,3‐diphenyl‐1H‐pyrazol‐4‐yl)propan‐2‐ol	 (8):	
Color:	White	plates.	Yield:	80	%.	M.p.:	92	 °C	 (cyclohexane).	 IR	
(KBr,	ν,	cm‐1):	3340	(OH)	(alcohol),	3060	(CH)	(Aromatic),	2975	
(CH)	 (alkyl),	 1610,	 1560,	 1450,	 1445	 (C=C)	 (Aromatic),	 1375,	
1330,	 760.	 1H	 NMR	 (400	 MHz,	 CDCl3,	 δ,	 ppm):	 1.40	 (s,	 6H,	
2CH3),	 3.5	 (s,	 1H,	 OH	 exchangeable	 with	 D2O)	 7.50‐8.60	 (m,	
10H,	Ar‐H).	MS	(EI,	m/z	(%)):	314	(M++2,	6),	312	(M+,	17),	310	
(40),	 294	 (100),	 277	 (61),	 253	 (82),	 235	 (52),	 194	 (42),	 180	
(35),	177	(18),	168	(14),	158	(37),	103	(33),	91	(27),	77	(27).	
Anal.	calcd.	for	C18H17ClN2O:	C,	69.12;	H,	5.48;	N,	8.96.	Found;	C,	
69.31;	H,	5.26;	N,	8.82%.	

4‐(2‐Hydroxy‐2‐methylpropyl)‐1,3‐diphenyl‐1H‐pyrazol‐5	
(4H)‐one	(12a):	Color:	Pale	yellow	viscous	oil.	Yield:	81	%.	nD25	
=	 1.597.	 IR	 (Film,	 ν,	 cm‐1):	 3440	 (OH)	 (alcohol),	 3035	 (CH)	
(Aromatic),	2970	(CH)	(alkyl),	1665	(C=O)	(amide),	1600,	1580,	
1455,	 1445	 (C=C)	 (Aromatic),	 1390,	 1330,	 745.	 1H	NMR	 (400	
MHz,	CDCl3,	δ,	ppm):	1.30	(s,	6H,	2CH3),	1.74	(app.	t,	2H,	J	=	14.2	
Hz,	CH2),	2.55	(s,	1H,	OH	exchangeable	with	D2O),	2.65	(t,	1H,	J	=	
14.2	Hz,	CH),	7.25‐8.22	(m,	10H,	Ar‐H).	MS	(EI,	m/z	(%)):	308	

(M+,	13),	290	(100),	249	(55),	231	(41),	235	(55),	193	(20),	180	
(29),	178	(15),	167	(11),	158	(35),	103	(24),	90	(22),	77	(44).	
Anal.	calcd.	for	C19H20N2O2:	C,	74.00;	H,	6.54;	N,	9.08.	Found;	C,	
74.18;	H,	6.40;	N,	9.10%.	

4‐(3‐Hydroxy‐3‐methylbutan‐2‐yl)‐1,3‐diphenyl‐1H‐pyrazol‐
5(4H)‐one	(12b):	Color:	Cream	plates.	Yield:	84	%.	M.p.:	84	°C	
(benzene).	IR	(KBr,	ν,	cm‐1):	3425	(OH)	(br,	alcohol),	3060	(CH)	
(Aromatic),	2965	(CH)	(alkyl),	1668	(C=O)	(amide),	1594,	1580,	
1455,	 1440	 (C=C)	 (Aromatic),	 1385,	 1320,	 743.	 1H	NMR	 (400	
MHz,	CDCl3,	δ,	ppm):	0.90	(d,	3H,	 J	=	9.4	Hz,	CH3),	1.27	(s,	6H,	
2CH3),	 1.85	 (p,	 1H,	 J	 =	 12.5	 Hz,	 ‐CH),	 2.10	 (s,	 1H,	 OH	
exchangeable	with	D2O),	2.42	(d,	1H,	J	=	12.5	Hz,	CH),	7.15‐8.25	
(m,	10H,	Ar‐H).	MS	(EI,	m/z	(%)):	322	(M+,	10),	304	(100),	263	
(31),	245	(75),	248	(62),	235	(33),	194	(37),	180	(20),	177	(14),	
168	(21),	158	(48),	103	(23),	91	(35),	77	(47).	Anal.	calcd.	for	
C20H22N2O2:	C,	74.51;	H,	6.88;	N,	8.69.	Found;	C,	74.62;	H,	6.69;	
N,	8.63%.	

4‐(5‐Chloro‐1,3‐diphenyl‐1H‐pyrazol‐4‐yl)‐2‐methylbutan‐2‐
ol	 (16a):	 Color:	 White	 needles.	 Yield:	 85	 %.	 M.p.:	 118	 °C	
(benzene).	 IR	 (KBr,	 ν,	 cm‐1):	 3490	 (OH)	 (alcohol),	 3075	 (CH)	
(Aromatic),	 2990	 (CH)	 (alkyl),	 1610,	 1490,	 1455,	 1430	 (C=C)	
(Aromatic),	1386,	1355,	1020,	745.	1H	NMR	(400	MHz,	CDCl3,	δ,	
ppm):	1.10	 (s,	6H,	2CH3),	1.55	(t,	2H,	 J	=	6.2	Hz,	CH2),	1.80	(s,	
1H,	 OH	 exchangeable	with	D2O),	 2.40	 (t,	 2H,	 J	=	 6.2	Hz,	 CH2),	
7.22‐8.30	(m,	10	H,	Ar‐H).	MS	(EI,	m/z	(%)):	342	(M++2,	9),	340	
(M+,	22),	338	(48),	322	(100),	281	(51),	267	(42),	263	(12),	253	
(70),	245	(38),	235	(18),	194	(42),	180	(11),	176	(19),	167	(30),	
159	 (43),	 103	 (13),	 91	 (38),	 77	 (39).	 Anal.	 calcd.	 for	
C20H21ClN2O:	C,	70.48;	H,	6.21;	N,	8.22.	Found;	C,	70.49;	H,	6.26;	
N,	8.05%.	

4‐(5‐Chloro‐1,3‐diphenyl‐1H‐pyrazol‐4‐yl)‐2,3‐dimethyl	
butan‐2‐ol	(16b):	Color:	Reddish	viscous	oil.	Yield:	81	%.	nD25	=	
1.619.	 IR	 (Film,	 ν,	 cm‐1):	 3465	 (OH)	 (alcohol),	 3055	 (CH)	
(Aromatic),	 2973	 (CH)	 (alkyl),	 1590,	 1480,	 1455,	 1440	 (C=C)	
(Aromatic),	1345,	745.		

	



282	 El‐Aal	et	al.	/	European	Journal	of	Chemistry	5	(2)	(2014)	277‐286	
	

	
Table	2.	Friedel‐Crafts	ring	closures	of	heterocyclic	alkanols	8,	12a,b	and	16a,b.	
Entry	 Substrate	 Product	 Conditions	 Yield	(%)	a	
1	

N
N

Ph

Ph
HO

8
Cl

	

	

AlCl3/CH3NO2b,	DCMc,20	h,	rt 86	
P2O5d,	Toluene,	8	h,	reflux 75	
PPAe,	4	h,	200‐210	°C	 72	

2	

N
N

Ph

Ph

O

OH

12a 	 	

AlCl3/CH3NO2,	DCM,	4	h,	rt	 92 
P2O5,	PhH,	5	h,	reflux	 83	
PPA,	2	h,	180‐190	°C	 75	

3	

	

N
N
Ph

O

2b 	

AlCl3/CH3NO2,	DCM,	4	h,	rt	 85	
P2O5,	PhH,	3	h,	reflux	 80	
PPA,	2	h,	200‐210	°C	 76	

4	

	

N N
Ph

Cl

3a 	

AlCl3/CH3NO2,	DCM,	1	h,	rt 83	
P2O5,	PhH,	5	h,	reflux 79	
PPA,	1h,	180‐190	°C 74	

5	

16b

N
N

Ph

Ph

Cl

OH

	

N
N
Ph

Cl

3b 	

AlCl3/CH3NO2,	DCM,	1	h,	rt 86	
P2O5,	PhH,	4	h,	reflux	 80	
PPA,	1	h,	200‐210	°C	 77	

a	Isolated	yield	refer	to	substrate.	
b	With	AlCl3/CH3NO2	catalyst	reactant	proportions	were:	carbinol	or	acid	(0.002	moe),	AlCl3	(0.0024	mol),	CH3NO2	(0.024	mol),	solvent	(10	mL).		
c	Dichloromethane.	
d	With	P2O5	catalyst	reactant	proportions	were:	carbinol	or	acid	(0.4	g)	and	P2O5	(4	g)	in	anhydrous	toluene	or	benzene	(15	mL).	
e	With	PPA	catalyst	reactant	proportions	were:	carbinol	or	acid	(0.5	g)	and	PPA	(5	g).	
	
	

1H	NMR	(400	MHz,	CDCl3,	δ,	ppm):	0.95	(d,	3H,	J	=	10.4	Hz,	
CH3),	1.30	 (s,	6H,	2CH3),	2,21	(dt,	1H,	 J	=	9.3	Hz,	 ‐CH),	2.42	(t,	
Ha,	J	=	16.3	Hz,	CH2),	2.64	(app.t,	Hb,	J	=	16.3	Hz,	CH2),	2.50	(s,	
1H,	OH	exchangeable	with	D2O),	7.22‐8.15	(m,	10	H,	Ar‐H).	MS	
(EI,	m/z	(%)):	356	(M++2,	5),	354	(M+,	13),	336	(100),	295	(74),	
280	(48),	267	(35),	252	(84),	245	(24),	235	(13),	194	(48),	180	
(14),	176	(26),	167	(35),	159	(52),	103	(15),	91	(48),	77	(42).	
Anal.	calcd.	for	C21H23ClN2O:	C,	71.07;	H,	6.53;	N,	7.89.	Found;	C,	
71.11;	H,	6.53;	N,	7.65%.	
	
2.2.9.	Friedel‐Crafts	cyclialkylations	procedures	
	

The	 procedures	 [46‐54]	 described	 earlier	 for	
cyclialkylation	of	acids	and	alcohols	with	AlCl3/CH3NO2	or	P2O5	
or	PPA	catalysts	were	essentially	followed.	In	all	reactions,	the	
crude	 oily	 or	 solid	 products	 were	 purified	 by	 flash	 column	
chromatography	(basic	alumina,	EtOAc:n‐hexane,	3:1,	v:v)	gave	
the	 pure	 products	 1a,b,	 2a‐d	 and	 3a‐d.	 The	 conditions	 and	
yields	 for	 all	 products	 are	 shown	 in	 Table	 2	 and	 3	while	 the	
physical	and	spectral	data	of	the	products	are	given	below.	

3‐Chloro‐2,4‐dihydro‐4,4‐dimethyl‐2‐phenylindeno[1,2‐c]	
pyrazole	(1a):	Color:	White	needles.	M.p.:	117	°C	(acetone).	 IR	
(KBr,	ν,	cm‐1):	3075	(CH)	(Aromatic),	2980	(CH)	(alkyl),	1600,	
1480,	1460,	1435	(C=C)	 (Aromatic),	1355,	1220,	748.	1H	NMR	
(400	MHz,	CDCl3,	δ,	ppm):	1.42	(s,	6H,	2CH3),	7.15‐8.35	(m,	9H,	
Ar‐H).	 13C	NMR	(100	MHz,	CDCl3,	δ,	ppm):	27.6	 (1C,	 ‐C(CH3)2),	
31.4	(2C,	‐C(CH3)2),	117.4	(1C,	C‐3a),	123.4	(2C,	Ar.,	C‐2',	C‐6'),	
126.3	 (1C,	 Ar.,	 C‐4'),	 126.7	 (1C,	 Ar.,	 C‐7),	 127.4	 (1C,	 Ar.,	 C‐5),	
128.2	(1C,	N‐C(Cl)=,	C‐3),	129.2	(1C,	Ar.,	C‐8),	129.4	(1C,	Ar.,	C‐
6),	 132.4	 (2C,	 Ar.,	 C‐3',	 C‐5'),	 134.7	 (1C,	 Ar.,	 C‐8a),	 142.7	 (1C,	
Ar.,	 C‐1'),	 156.1	 (1C,	 N=C‐,	 C‐8b),	 160.4	 (1C,	 Ar.,	 C‐4a).	 Anal.	
calcd.	for	C18H15ClN2:	C,	73.34;	H,	5.13;	N,	9.50.	Found;	C,	73.38;	
H,	5.14;	N,	9.37%.	

4,5‐Dihydro‐5,5‐dimethyl‐2‐phenyl‐2H‐benzo[g]indazol‐3	
(3aH)‐one	(2a):	Color:	White	needles.	M.p.:	92	°C	(acetone).	 IR	
(KBr,	 ν,	 cm‐1):	 3090	 (CH)	 (Aromatic),	 2980	 (CH)	 (alkyl),	 1674	
(C=O)	(amide),	1600,	1475,	1465,	1440	(C=C)	(Aromatic),	1350,	
750.	1H	NMR	(400	MHz,	CDCl3,	δ,	ppm):	1.40	(s,	6H,	2CH3),	1.84	
(t,	1Ha,	J	=	14.2	Hz,	CH2),	2.17	(dd,	1Hb,	J	=	14.2	Hz,	CH2),	2.35	
(app.	q,	1H,	J	=	10.4	Hz,	CH),	6.85‐8.11	(9H,	m,	Ar‐H).	13C	NMR	
(100	 MHz,	 CDCl3,	 δ,	 ppm):	 29.2	 (2C,	 ‐C(CH3)2),	 33.4	 (1C,	 ‐
C(CH3)2),	 43.6	 (1C,	 ‐CH2‐,	C‐4),	44.3	 (1C,	 ‐CH‐CO‐,	C‐3a),	122.5	
(2C,	 Ar.,	 C‐2',	 C‐6'),	 124.4	 (1C,	 Ar.,	 C‐4'),	 125.2	 (1C,	 Ar.,	 C‐6),	
126.4	 (1C,	Ar.,	 C‐9a),	 127.6	 (1C,	Ar.,	 C‐8),	 128.8	 (1C,	Ar.,	 C‐9),	
131.4	(2C,	Ar.,	C‐3',	C‐5'),	133.7	(1C,	Ar.,	C‐7),	144.4	(1C,	Ar.,	C‐
1'),	153.7	(1C,	N=C‐,	C‐9b),	157.5	(1C,	Ar.,	C‐5a),	178.2	(1C,	C=O,	
C‐3).	 Anal.	 calcd.	 for	 C19H18N2O:	 C,	 78.59;	 H,	 6.25;	 N,	 9.65.	
Found;	C,	78.55;	H,	6.37;	N,	9.49%.	

4,5‐Dihydro‐4,5,5‐trimethyl‐2‐phenyl‐2H‐benzo[g]indazol‐
3(3aH)‐one	 (2b):	 Color:	 Reddish	 viscous	 oil.	 nD25	 =	 1.592.	 IR	
(Film,	ν,	cm‐1):	3062	(CH)	(Aromatic),	2955	(CH)	(alkyl),	1665	
(C=O)	(amide),	1590,	1490,	1470,	1445	(C=C)	(Aromatic),	1345,	
7453.	1H	NMR	(400	MHz,	CDCl3,	δ,	ppm):	1.10	(d,	3H,	J	=	9.4	Hz,	
CH3),	1.37	(s,	6H,	2CH3),	2.21	(p,	1H,	J	=	12.5	Hz,	CH),	2.38	(app.	
t,	1H,	 J	=	12.5	Hz,	CH),	7.19‐8.35	(m,	9H,	Ar‐H).	 13C	NMR	(100	
MHz,	 CDCl3,	 δ,	 ppm):	 14.2	 (1C,	 ‐CH(CH3)),	 28.3	 (2C,	 ‐C(CH3)2),	
37.6	 (1C,	 ‐C(CH3)2,	 C‐5),	 42.8	 (1C,	 ‐C(CH3),	 C‐4),	 44.2	 (1C,	 ‐
COCH‐,	 C‐3a),	 121.8	 (2C,	 Ar.,	 C‐2',	 C‐6'),	 124.8	 (1C,	 Ar.,	 C‐4'),	
125.2	 (1C,	Ar.,	 C‐6),	 126.7	 (1C,	Ar.,	 C‐9a),	 127.2	 (1C,	Ar.,	 C‐8),	
128.8	(1C,	Ar.,	C‐9),	132.2	(2C,	Ar.,	C‐3',	C‐5'),	133.4	(1C,	Ar.,	C‐
7),	144.2	(1C,	Ar.,	C‐1'),	151.7	(1C,	N=C‐,C‐9b),	157.5	(1C,	Ar.,	C‐
5a),	181.3	(1C,	C=O,	C‐3).	Anal.	calcd.	for	C20H20N2O:	C,	78.92;	H,	
6.62;	N,	9.20.	Found;	C,	78.79;	H,	6.44;	N,	9.36%.	

3‐Chloro‐6,6‐dimethyl‐4,5,6‐trihydro‐2‐phenyl‐benzo[6,7]	
cyclohepta[1,2‐c]pyrazole	(3a):	Color:	Reddish	viscous	oil.	nD25	=	
1.589.		



El‐Aal	et	al.	/	European	Journal	of	Chemistry	5	(2)	(2014)	277‐286	 283	
 

	
Table	3.	Friedel‐Crafts	ring	closures	of	heterocyclic	acids	6	or	10a,b	or	14a,b.	
Entry	 Substrate	 Product	 Conditions Yield	(%)
1	

	
N
N Ph

O
Cl

1b 	

AlCl3/CH3NO2,	DCM,	18	h,	reflux	 90	
P2O5,Toluene,	6	h,	reflux 81	
PPA,	5	h,	210‐220	°C 77	

2	

	

AlCl3/CH3NO2,	DCM,	10	h,	reflux	 89 
P2O5,	Toluene,	6	h,	reflux	 82	
PPA,	4	h,	190‐200	°C	 73	

3	

N
N

Ph

Ph

10b

O

COOH

	
	

AlCl3/CH3NO2,	DCM,	8	h,	reflux 81	
P2O5,	Toluene,	3	h,	reflux 89	
PPA,	2	h,	200‐210	°C 79	

4	

	
	

AlCl3/CH3NO2,	DCM,	8	h,	reflux 92	
P2O5,	Toluene,	5	h,	reflux	 82	
PPA,	2h,	190‐200	°C	 79	

5	

	

AlCl3/CH3NO2,	DCM,	4	h,	reflux 88	
P2O5,	Toluene,	4	h,	reflux 81	
PPA,	2	h,	200‐210	°C 80	

	
	
	

IR	(Film,	ν,	cm‐1):	3090	(CH)	(Aromatic),	2980	(CH)	(alkyl),	
1604,	1485,	1465,	1442	(C=C)	 (Aromatic),	1350,	695.	1H	NMR	
(400	MHz,	CDCl3,	δ,	ppm):	1.27	(s,	6H,	2CH3),	1.75	(t,	2H,	J	=	6.2	
Hz,	CH2),	2.64	(t,	2H,	 J	=	6.2	Hz,	CH2),	7.21‐8.14	(9H,	m,	Ar‐H).	
13C	NMR	(100	MHz,	CDCl3,	δ,	ppm):	17.5	 (1C,	 ‐CH2‐,	C‐4),	31.5	
(2C,	 ‐C(CH3)2),	 42.6	 (1C,	 ‐C(CH3)2,	 C‐6),	 49.2	 (1C,	 ‐CH2‐,	 C‐5),	
119.3	(1C,	C‐3a),	122.4	(2C,	Ar.,	C‐2',	C‐6'),	125.6	(1C,	Ar.,	C‐7),	
125.8	(1C,	Ar.,	C‐10a),	126.2	(1C,	Ar.,	C‐9),	126.8	(1C,	Ar.,	C‐4'),	
127.4	(1C,	N‐C(Cl)=,	C‐3),	127.8	(1C,	Ar.,	C‐10),	128.4	(1C,	Ar.,	C‐
8),	131.2	(2C,	Ar.,	C‐3',	C‐5'),	142.7	(1C,	Ar.,	C‐1'),	149.1	(1C,	Ar.,	
C‐6a),	 154.5	 (1C,	 N=C‐,	 C‐10b).	 Anal.	 calcd.	 for	 C20H19ClN2:	 C,	
74.41;	H,	5.93;	N,	8.68.	Found;	C,	74.23;	H,	6.08;	N,	8.46%.	

3‐Chloro‐5,6,6‐trimethyl‐4,5,6‐trihydro‐2‐phenyl‐benzo[6,7]	
cyclohepta[1,2‐c]pyrazole	 (3b):	 Color:	 White	 needles.	 M.p.:	 83	
°C	 (benzene).	 IR	 (KBr,	 ν,	 cm‐1):	 3055	 (CH)	 (Aromatic),	 2954	
(CH)	 (alkyl),	 1600,	 1580,	 1480,	 1465	 (C=C)	 (Aromatic),	 1345,	
1285,	1020,	746.	1H	NMR	(400	MHz,	CDCl3,	δ,	ppm):	0.92	(d,	3H,	
J	=	6	Hz,	CH3),	1.35	(s,	6H,	2CH3),	2.33	(dd,	Ha,	J	=	16.3	Hz,	CH2),	
2.42	(p,	1H,	 J	=	9.3	Hz,	 ‐CH),	2.64	(app.t,	Hb,	J	=	16.3	Hz,	CH2),	
7.11‐8.25	 (m,	 9H,	 Ar‐H).	 13C	 NMR	 (100	 MHz,	 CDCl3,	 δ,	 ppm):	
16.4	(1C,	‐CHCH3),	27.3	(2C,	‐C(CH3)2),	29.2	(1C,	‐CH2‐,	C‐4),	42.5	
(1C,	 ‐C(CH3)2,	 C‐6),	 52.4	 (1C,	 ‐CHCH3,	 C‐5),	 119.2	 (1C,	 C‐3a),	
120.7	(2C,	Ar.,	C‐2',	C‐6'),	125.2	(1C,	Ar.,	C‐7),	125.6	(1C,	Ar.,	C‐
10a),	126.6	(2C,	Ar.,	C‐4',	C‐9),	127.2	(1C,	N‐C(Cl)=,	C‐3),	128.1	
(1C,	 Ar.,	 C‐10),	 128.9	 (1C,	 Ar.,	 C‐8),	 129.5	 (2C,	 Ar.,	 C‐3',	 C‐5'),	
142.7	 (1C,	 Ar.,	 C‐1'),	 151.4	 (1C,	 Ar.,	 C‐6a),	 157.4	 (1C,	 N=C‐,C‐
10b).	 Anal.	 calcd.	 for	 C21H21ClN2:	 C,	 74.88;	 H,	 6.28;	 N,	 8.32.	
Found;	C,	74.64;	H,	6.40;	N,	8.52%.	

3‐Chloro‐2‐phenylindeno[1,2‐c]pyrazol‐4(2H)‐one	 (1b):	
Color:	White	crystals.	M.p.:	144	°C	 (ethanol).	 IR	(KBr,	ν,	 cm‐1):	
3032	(CH)	(Aromatic),	2963	(CH)	(alkyl),	1687	(C=O)	(Ketone),	
1590,	1485,	1455,	1430	(C=C)	(Aromatic),	1385,	1260,	742.	1H	
NMR	 (400	 MHz,	 CDCl3,	 δ,	 ppm):	 7.27‐8.34	 (9H,	 m,	 Ar‐H).	 13C	
NMR	(100	MHz,	CDCl3,	δ,	ppm):	109.4	(1C,	C‐3a),	122.6	(2C,	Ar.,	
C‐2',	C‐6'),	126.8	(1C,	Ar.,	C‐4'),	127.4	(1C,	Ar.,	C‐8),	128.9	(1C,	
Ar.,	 C‐6),	 129.4	 (2C,	 Ar.,	 C‐3',	 C‐5'),	 130.6	 (1C,	 Ar.,	 C‐5),	 131.6	
(1C,	 N‐C(Cl)=,	 C‐3),	 135.8	 (1C,	 Ar.,	 C‐7),	 137.2	 (1C,	 Ar.,	 C‐4a).	
142.7	 (1C,	Ar.,	 C‐1'),	 145.2	 (1C,	Ar.,	 C‐8a),	 157.8	 (1C,	N=C‐,	C‐
8b),	197.4	(1C,	C=O,	C‐4).	Anal.	calcd.	for	C16H9ClN2O:	C,	68.46;	
H,	3.23;	N,	9.98.	Found;	C,	68.59;	H,	3.05;	N,	10.18%.	

3a,4‐Dihydro‐2‐phenyl‐2H‐benzo[g]indazole‐3,5‐dione	 (2c):	
Color:	Yellow	crystals.	M.p.:	126	°C	(ethanol).	IR	(KBr,	ν,	cm‐1):	
3035	(CH)	(Aromatic),	2985	(CH)	(alkyl),	1693	(C=O)	(ketone),	

1655	(C=O)	(amide),	1580,	1480,	1465	(C=C)	(Aromatic),	1345,	
746.	1H	NMR	(400	MHz,	CDCl3,	δ,	ppm):	2.71	(dt,	1Ha,	 J	=	14.2	
Hz,	CH2),	 2.84	 (dd,	 1H,	 J	 =	 10.4	Hz,	CH),	 3.11	 (app.	 t,	 1Hb,	 J	 =	
14.2	 Hz,	 CH2),	 7.32‐8.30	 (9H,	 m,	 Ar‐H).	 13C	 NMR	 (100	 MHz,	
CDCl3,	δ,	ppm):	38.6	(1C,	‐CH2‐,	C‐4),	42.3	(1C,	C‐3a),	122.8	(2C,	
Ar.,	C‐2',	C‐6'),	126.4	 (1C,	Ar.,	C‐4'),	128.3	 (1C,	Ar.,	C‐6),	129.6	
(2C,	 Ar.,	 C‐3',	 C‐5'),	 130.4	 (1C,	 Ar.,	 C‐9),	 130.9	 (1C,	 Ar.,	 C‐9a),	
132.1	 (1C,	Ar.,	 C‐7),	 133.5	 (1C,	Ar.,	 C‐8),	 138.7	 (1C,	Ar.,	 C‐5a),	
145.4	(1C,	Ar.,	C‐1'),	158.7	(1C,	N=C‐,C‐9b),	179.4	(1C,	N‐C=O,	C‐
3),	204.9	(1C,	C=O,	C‐5).	Anal.	calcd.	for	C17H12N2O2:	C,	73.90;	H,	
4.38;	N,	10.14.	Found;	C,	73.76;	H,	4.49;	N,	10.22%.	

3a,4‐Dihydro‐4‐methyl‐2‐phenyl‐2H‐benzo[g]indazole‐3,5‐
dione	 (2d):	 Color:	 White	 needles.	 M.p.:	 152	 °C	 (ethanol).	 IR	
(KBr,	 ν,	 cm‐1):	 3066	 (CH)	 (Aromatic),	 2964	 (CH)	 (alkyl),	 1705	
(C=O)	 (ketone),	 1663	 (C=O)	 (amide),1597,	 1575,	 1480,	 1444	
(C=C)	(Aromatic),	1385,	743.	1H	NMR	(400	MHz,	CDCl3,	δ,	ppm):	
1.18	(d,	3H,	J	=	9.4	Hz,	CH3),	2.93	(d,	1H,	J	=	12.5	Hz,	CH),	3.37	
(p,1H,	 J	 =	 6	 Hz,	 CH),	 7.23‐8.41	 (m,	 9H,	 Ar‐H).	 13C	 NMR	 (100	
MHz,	CDCl3,	δ,	ppm):	16.5	(1C,	‐CHCH3),	40.7	(1C,	‐CHCH3,	C‐4),	
46.4	(1C,	C‐3a),	122.6	(2C,	Ar.,	C‐2',	C‐6'),	126.4	(1C,	Ar.,	C‐4'),	
128.5	(1C,	Ar.,	C‐6),	129.2	(2C,	Ar.,	C‐3',	C‐5'),	130.2	(1C,	Ar.,	C‐
9),	131.3	(1C,	Ar.,	C‐9a),	132.8	(1C,	Ar.,	C‐7),	134.3	(1C,	Ar.,	C‐8),	
137.7	 (1C,	 Ar.,	 C‐5a),	 144.4	 (1C,	 Ar.,	 C‐1'),	 157.7	 (1C,	 N=C‐,C‐
9b),	 182.4	 (1C,	N‐C=O,	 C‐3),	 207.2	 (1C,	 C=O,	 C‐5).	 Anal.	 calcd.	
for	 C18H14N2O2:	 C,	 74.47;	 H,	 4.86;	 N,	 9.65.	 Found;	 C,	 74.53;	H,	
5.07;	N,	9.53%.	

3‐Chloro‐4,5,6‐trihydro‐2‐phenyl‐benzo[6,7]cyclohepta[1,2‐
c]pyrazol‐6‐one	 (3c):	 Color:	 White	 needles.	 M.p.:	 91	 °C	
(acetone).	 IR	 (KBr,	 ν,	 cm‐1):	 3070	 (CH)	 (Aromatic),	 2978	 (CH)	
(alkyl),	 1694	 (C=O)	 (ketone),	 1585,	 1463,	 1450	 (C=C)	
(Aromatic),	1385,	1280,	1075,	745.	1H	NMR	(400	MHz,	CDCl3,	δ,	
ppm):	1.62	(t,	2H,	J	=	6.2	Hz,	CH2),	2.84	(t,	2H,	J	=	6.2	Hz,	CH2),	
7.19‐8.30	 (m,	 9H,	 Ar‐H).	 13C	 NMR	 (100	 MHz,	 CDCl3,	 δ,	 ppm):	
13.8	 (1C,	 ‐CH2‐,	 C‐4),	 52.4	 (1C,	 ‐CH2‐,	 C‐5),	 119.3	 (1C,	 C‐3a),	
123.2	 (2C,	 Ar.,	 C‐2',	 C‐6'),	 126.8	 (1C,	 Ar.,	 C‐4'),	 127.4	 (1C,	 N‐
C(Cl)=,	 C‐3),	 127.6	 (1C,	 Ar.,	 C‐10),	 128.2	 (1C,	 Ar.,	 C‐8),	 129.6	
(1C,	Ar.,	C‐7),	130.4	 (2C,	Ar.,	C‐3',	C‐5'),	132.7	 (1C,	Ar.,	C‐10a),	
135.7	(1C,	Ar.,	C‐9),	138.9	(1C,	C‐6a),	143.7	(1C,	Ar.,	C‐1'),	156.4	
(1C,	 N=C‐,	 C‐10b),	 208.3	 (1C,	 C=O,	 C‐6).	 Anal.	 calcd.	 for	
C18H13ClN2O:	C,	70.02;	H,	4.24;	N,	9.07.	Found;	C,	69.79;	H,	4.42;	
N,	9.35%.	

3‐Chloro‐4,5,6‐trihydro‐5‐methyl‐2‐phenyl‐benzo[6,7]cyclo	
hepta[1,2‐c]pyrazol‐6‐one	(3d):	Color:	White	needles.		



284	 El‐Aal	et	al.	/	European	Journal	of	Chemistry	5	(2)	(2014)	277‐286	
	

	

N
N

Ph

R

8: n = 0
16a: n = 1, R = H
16b: n = 1, R = Me

N
N

Ph

Ph

Cl

R

OH

n

N
N

Ph

Ph

Cl

R
n

H+, -H2O

Cat. -H+

N
N

Ph

or

3a: R = H
3b: R = Me

17a-c

Cl Cl

1a
 

	
Scheme	3

	
	

 
	

Scheme	4
	
	

 

Scheme	5	
	
	
M.p.:	 164	 °C	 (acetone).	 IR	 (KBr,	 ν,	 cm‐1):	 3060	 (CH)	

(Aromatic),	2965	(CH)	(alkyl),	1686	(C=O)	(ester),	1590,	1470,	
1450	 (C=C)	 (Aromatic),	 1385,	 1285,	 1070,	 750,	 695.	 1H	NMR	
(400	MHz,	CDCl3,	 δ,	ppm):	1.19	 (d,	3H,	 J	 =	10.4	Hz,	CH3),	2.64	
(td,	Ha,	J	=	16.3	Hz,	CH2),	2.81	(p,	Hb,	J	=	16.3	Hz,	CH2),	3.	42	(q,	
1H,	J	=	9.3	Hz,	‐CH),	7.30‐8.35	(m,	9H,	Ar‐H).	13C	NMR	(100	MHz,	
CDCl3,	 δ,	 ppm):	 19.4	 (1C,	 ‐CHCH3),	 29.5	 (1C,	 ‐CH2‐,	 C‐4),	 47.2	
(1C,	 ‐CHCH3,	 C‐5),	 118.5	 (1C,	 C‐3a),	 123.4	 (2C,	 Ar.,	 C‐2',	 C‐6'),	
126.8	(1C,	Ar.,	C‐4'),	127.2	(1C,	N‐C(Cl)=,	C‐3),	128.2	(1C,	Ar.,	C‐
10),	128.9	(1C,	Ar.,	C‐8),	129.2	(1C,	Ar.,	C‐7),	130.3	(2C,	Ar.,	C‐3',	
C‐5'),	131.7	(1C,	Ar.,	C‐10a),	134.7	(1C,	Ar.,	C‐9),	138.9	(1C,	Ar.,	
C‐6a),	144.5	(1C,	Ar.,	C‐1'),	157.3	(1C,	N=C‐,	C‐10b),	208.2	(1C,	
C=O,	C‐6).	Anal.	calcd.	for	C19H15ClN2O:	C,	70.70;	H,	4.68;	N,	8.68.	
Found;	C,	70.92;	H,	4.45;	N,	8.52%.	
	
3.	Results	and	discussion		
	

We	 first	 attempted	 to	 prepare	 the	 precursors	 heteroaryl	
acids	 required	 for	 this	 work	 (6,	10a,b	 and	14a,b)	 which	 are	
easily	 obtained	 via	 three	 different	 synthetic	 routes	 starting	
from	 the	 easily	 prepared	 1,3‐diphenyl‐1H‐pyrazol‐5(4H)‐one	
(4)	[56]	as	formulated	in	Scheme	1	and	2.	

The	 first	 path	 comprised	 the	 formation	 of	 5‐chloro‐1,3‐
diphenyl‐1H‐pyrazole‐4‐carbaldehyde	 (5)	 following	 standard	
literature	 procedure	 by	 chloroformylation	 of	 pyrazolone	 4	
under	Vilsmeier	conditions	[55].	This	aldehyde	was	oxidized	by	
KMnO4	 solution	 [57]	 to	 afford	 5‐chloro‐1,3‐diphenyl‐1H‐
pyrazole‐4‐carboxylic	 acid	 (6).	 The	 second	 path	 included	 the	
conversion	of	substrate	4	to	4‐bromo‐1,3‐diphenyl‐1H‐pyrazol‐

5(4H)‐one	 (9)	 following	 the	 literature	 procedure	 [58]	 in	 the	
presence	 of	 bromine	 in	 acetic	 acid.	 The	 resulting	 bromide	 9	
was	 allowed	 to	 react	 with	 excess	 of	 sodio‐diethyl	 malonates	
[59]	 in	 ethanol	 followed	 by	 decarboxylation	 to	 afford	
substituted	acetic	acids	10a,b.	

On	 the	 other	 hand,	 the	 third	 route	 (path	 3)	 involved	 the	
production	 of	 acid	 precursors	14a,b	 (Scheme	 2).	 These	 acids	
were	smoothly	prepared	through	the	Perkin‐type	reaction	[60]	
of	 aldehyde	 5	 with	 acid	 anhydrides	 and	 the	 corresponding	
sodium	 salts	 of	 acids	 to	 give	 substituted	 3‐(5‐chloro‐1,3‐
diphenyl‐1H‐pyrazol‐4‐yl)acrylic	 acids	 (11a,b).	 The	 resulting	
acids	 13a,b	 were	 reduced	 by	 sodium	 amalgam	 in	 sodium	
hydroxide	solution	to	afford	14a,b.	

Upon	 intermediate	 acids	 6,	 10a,b	 and	 14a,b	 are	 formed,	
they	could	be	converted	into	ethyl	esters	7,	11a,b	and	15a,b	by	
reaction	with	ethanol	and	H2SO4	[61].	The	resulting	esters	were	
converted	 to	 the	 corresponding	 alcohols	 8,	 12a,b	 and	 16a,b	
(Schemes	1	 and	2;	Table	1)	 by	addition	of	 two	equivalents	 of	
methymagnesium	 iodide	 [62]	 in	 Et2O/THF	 solution.	 The	
structures	 of	 all	 new	 alcohols	were	 appropriately	 established	
by	the	usual	spectroscopic	methods.	

	The	structural	elucidation	of	alcohols	8,	12a,b,	 and	16a,b	
was	mainly	based	on	 IR,	 1H	NMR,	MS	and	 elemental	 analyses.	
The	IR	spectra	of	alcohols	1a‐c	showed	absorption	bands	for	a	
OH	groups	as	broad	bands	in	the	range	3340‐3490	cm‐1.	The	1H	
NMR	 data	 allowed	 an	 unambiguous	 statement	 of	 the	
heterocyclic	 alkanols	 formation.	 Thus,	 the	 1H	 NMR	 spectrum	
displayed	 five	 signals	 for	 compound	12a.	 The	 tenth	 aromatic	
protons	appear	at	δ	7.15‐8.25	ppm.		



El‐Aal	et	al.	/	European	Journal	of	Chemistry	5	(2)	(2014)	277‐286	 285	
 

	

 
	

Figure	2.	Diastereotopic	protons	embraced	in	pyrazolones	heteropolycycles.
	
	
The	 aliphatic	 acyclic	 protons	 of	 the	 two	 methyls	 and	

methylene	groups	of	 the	new	alcohol	 appeared	as	 two	sets	of	
splitting.	The	singlet	gem‐dimethyls	appear	at	δ	1.30	ppm	while	
doublet	at	δ	2.0	ppm	was	assigned	to	the	up‐field	proton	CH2.	A	
forth	broad	singlet	at	δ	2.55	ppm	was	assigned	to	OH.	In	all	IR	
spectra	of	the	synthesized	carbinols,	 the	characteristic	peak	of	
carbonyl	groups	was	absent.	

The	 cyclialkylations	 of	 alcohols	 8,	 12a,b	 and	 16a,b	 were	
smoothly	carried	out	 in	 the	presence	of	AlCl3/CH3NO2	or	P2O5	
or	 PPA	 catalysts	 under	 different	 reaction	 conditions	 gave	
substituted	 2,4‐dihydroindeno[1,2‐c]pyrazole	1a,	 4,5‐dihydro‐
2H‐benzo[g]indazol‐3(3aH)‐ones	 2a,b	 and	 4,5,6‐trihydro	
benzo[6,7]cyclohepta[1,2‐c]pyrazoles	 3a,b	 in	 good	 overall	
yields	(Table	2,	Scheme	3	and	4).	

On	 the	 other	 hand,	 cyclialkylations	 of	 acids	 6,	10a,b	 and	
14a,b	 were	 carried	 out	 in	 the	 presence	 of	 the	 same	 catalysts	
under	 varying	 conditions	 to	 give	 substituted	 tricyclic	
pyrazolones	 1b,	 2c,d	 and	 3c,d.	 The	 results	 are	 embedded	 in	
Table	2	and	Scheme	5.		

The	1H	NMR	data	allowed	an	unambiguous	statement	of	the	
formation	 of	 heterocyclic	 products.	 The	 assignment	 of	 the	
diastereotopic	protons	of	the	methylene	group	directly	bonded	
to	 pyrazole	 or	 pyrazolone	 rings	 (2a,c	 and	 3b,d)	 beside	 their	
intermediates	 alcohols	 and	 acids	 (12a,	 16b	 and	 10a,	 14b)	
were	made	on	the	basis	of	J‐values	that	were	obtained	by	direct	
inspection	 of	 the	 1H	 NMR	 spectrum	 which	 in	 turn	 showed	 a	
greatly	change	in	chemical	shifts.	It	is	known	that	the	extent	of	
shielding	is	proportional	to	the	electronegativity	exerted	by	the	
heterocyclic	 ring	 or	 the	 neighbored	 functional	 groups	 and	 its	
proximity	to	the	hydrogen	[63‐66].		

This	 trend	 has	 been	 observed	 from	 the	 chemical	 shifts	 of	
diastereotopic	 hydrogens	 (Ha	 and	 Hb)	 of	 CH2	 group	
characterized	by	the	A2B	system	obtained	in	each	series	(Figure	
2).	

For	 instance,	 the	 1H	 NMR	 of	 tricyclic	 compound	 2a	
displayed	five	signals	in	which	aromatic	protons	appeared	at	δ	
6.85‐8.11	 ppm	 and	 the	 gem‐dimethyls	 groups	 appeared	 as	
singlet	at	δ	1.40	ppm,	respectively.	The	third	quartet	appeared	
at	2.35	ppm	with	coupling	constant	of	10.4	Hz.	As	expected,	the	
remaining	two	signals	for	the	diastereotopic	CH2	group	exhibits	
a	complex	set	of	overlapped	signals	which	were	assigned	to	be	
shielded	and	displayed	as	a	second	order	set	of	signals	showed	
a	 triplet	 in	 average	 at	 δ	 1.84	 ppm	 with	 coupling	 constant	 of	
14.2	Hz	for	one	hydrogen	and	doublet	of	doublets	at	an	average	
of	 2.17	 ppm	 for	 the	 other	 one.	 In	 comparison	 with	 the	
compound	2a,	 the	tricyclic	pyrazolone	2c	showed	the	1H	NMR	
chemical	shifts	for	CH2	protons	(Ha	and	Hb)	as	a	characteristic	
doublet	 of	 triplet	 for	 Ha	 at	 an	 average	 of	 δ	 2.71	 ppm	with	 a	
coupling	 constant	 of	 14.2	 Hz	 and	 a	 apparently	 triplet	 for	 Hb	
near	δ	3.11	ppm.		
	
4.	Conclusion	

	
In	 conclusion,	we	 have	 developed	 a	 simple	 and	 attractive	

method	 for	 the	 synthesis	 of	 variety	 of	 new	 fused	 tricyclic	
pyrazoles	 bearing	 small	 to	 medium‐sized	 alkyl	 residues.	 The	
synthetic	 approach	 involved	 Friedel‐Crafts	 cyclialkylations	 of	

heteroaryl	 alkanols	 and	 acids	 catalyzed	 by	 AlCl3/CH3NO2	 or	
P2O5	or	PPA.	To	the	best	of	our	knowledge,	this	is	the	first	time	
that	such	novel	substituted	pyrazoles	have	been	described.	The	
results	 proved	 that	 Friedel‐Crafts	 cyclialkylations	 can	 be	
considered	 as	 useful	 pathways	 to	 the	 syntheses	 of	
heteropolycycles.	

	
Acknowledgements	
	

The	 authors	 are	 grateful	 for	 the	 financial	 support	 and	 all	
the	 facilities	 received	while	performing	and	writing	 this	work	
by	 the	 Chemistry	 Department,	 Faculty	 of	 Science	 Assiut	
University,	Assiut,	Egypt.		
	
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