untitled


European	Journal	of	Chemistry	2	(2)	(2011)	272‐275	

	
European	Journal	of	Chemistry	

ISSN	2153‐2249	(Print)	/	ISSN	2153‐2257	(Online)		2011	EURJCHEM	
DOI:10.5155/eurjchem.2.2.272‐275.359	

	
	

	

	

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

	 	 	

β‐Cyclodextrin	mediated	synthesis	of	1,8‐dioxooctahydroxanthenes	in	water	

Swapna	Kokkirala,	Narayana	Murthy	Sabbavarapu	and	Venkata	Durga	Nageswar	Yadavalli*	

Organic	Chemistry	Division‐I,	Indian	Institute	of	Chemical	Technology,	Hyderabad,	500607,	India	

*Corresponding	author	at:	Organic	Chemistry	Division‐I,	Indian	Institute	of	Chemical	Technology,	Hyderabad,	500607,	India.	Tel.:	+91.40.27191654;		
fax:	+91.40.27160512.	E‐mail	address:	dryvdnageswar@gmail.com	(V.D.N.	Yadavalli).	

	
	

	 	

	 	 	
COMMUNICATION	 INFORMATION	 	 ABSTRACT
Received:	02	December	2010	
Received	in	revised	form:	22	December	2010	
Accepted:	05	January	2011	
Online:	30	June	2011	

KEYWORDS	

	 An	experimentally	simple,	efficient	Michael	addition	reaction	was	developed	for	the	synthesis
of	 various	 1,8‐dioxooctahydroxanthene	 derivatives	with	 1,3‐cyclohexanedione/5,5‐dimethyl
1,3‐cyclohexane	dione	and	different	aldehydes	by	using	β‐cyclodextrin	as	a	catalyst	in	water.	A
biomimetic	approach	was	employed	and	the	corresponding	products	were	obtained	in	good
to	excellent	yields.	β‐cyclodextrin	can	be	recovered	and	reused	upto	four	cycles	without	loss
of	catalytic	activity.	

β‐Cyclodextrin		
Condensation		
Aromatic	aldehydes		
1,3‐Cyclohexanedione		
5,5‐Dimethyl‐1,3‐cyclohexanedione		
Water	

	
1.	Introduction	
	

Xanthenes	 and	 benzoxanthenes	 are	 important	 class	 of	
compounds	 that	 are	 found	 in	 numerous	 biologically	 active	
molecules.	This	structural	motif	has	also	been	investigated	for	a	
wide	 range	 of	 activities	 such	 as	 bactericidal	 [1],	 anti‐
inflammatory	 [2],	 antiviral	 [3],	 as	 well	 as	 photodynamic	
therapy	 [4],	 In	 particular,	 the	 xanthenedione	 structure	 is	
present	 in	 a	 number	 of	 natural	 products	 [5],	 and	 has	 been	 a	
component	 of	 dyes	 [6],	 fluorescent	materials	 for	 visualization	
of	 biomolecules	 and	 in	 laser	 technologies	 due	 to	 their	
spectroscopic	properties	 [7‐9].	Consequently,	several	methods	
have	been	developed	for	the	synthesis	of	xanthene	derivatives,	
which	 in	 general	 can	 be	 obtained	 by	 the	 condensation	 of	
appropriate	 active	 methylene	 derivatives	 with	 aldehydes	
catalyzed	by	mineral	acids	[10].	Xanthenes	were	also	prepared	
by	the	cyclization	of	polycyclic	aryltriflate	esters	[11],	catalyzed	
by	 palladium	 or	 the	 reaction	 of	 aryl	magnesium	 halides	 with	
triethylorthoformate	 [12,13].	 Li	 et	 al.	 reported	 solid	 state	
condensation	 reaction	 between	 5,5‐dimethyl‐1,3‐cyclohaxane‐
dione	and	aldehyde	by	grinding	at	room	temperature	[14].	Hua	
et	 al.	 and	 Jin	 et	 al.	 described	 the	 synthesis	 of	 xanthenes	
catalyzed	by	p‐dodecylbenzenesulfonic	 acid	 in	 aqueous	media	
[15,16].	 Jin	et	al.	and	Khosropour	et	al.	 reported	the	synthesis	
of	 xanthene	 and	 benzoxanthene	 in	 presence	 of	 p‐toluene‐
sulfonic	 acid	 as	 a	 catalyst	 in	 organic	 solvent	 [17,18].	 Other	
methods	 developed	 for	 the	 synthesis	 of	 1,8‐dioxooctahydro‐
xanthenes	 include	 the	 use	 of	 NaHSO4‐SiO2	 (or)	 silica	 chloride	
[19],	Amberlyst‐15	[20],	Dowex50w	[21],	Montmorillonite	[22],	
cyanuric	 chloride	 [23],	 BiCl3	 [24],	 Fe+3‐montmorillonite	 [25],	
polyaniline‐p‐toluenesulfonate	[26],	PMA‐SiO2	[27],	HClO4‐SiO2	
&	 PPA‐SiO2	 [28],	 ZrOCl2	 [29],	 H3PW12O40	 [30],	 LiBr	 [31],	 and	
proline	 triflate	 [32],	 as	 catalysts.	 Literature	 survey	 also	
indicates	 the	 role	 of	 ionic	 liquids	 [33,34],	 and	 acidic	 ionic	
liquids	 in	 aqueous	media	 [35],	 in	 the	 synthesis	 of	 xanthenes.	

However,	 these	 existing	 methodologies	 suffer	 from	 many	
drawbacks	 such	 as	 use	 of	 toxic	 organic	 solvents,	 drastic	
reaction	 conditions,	 and	 expensive	 reagents/catalysts	 as	 well	
as	low	yields.	

Aqueous	 phase	 organic	 synthesis	 has	 attracted	 the	
attention	 of	 chemists	 as	 it	 overcomes	 the	 harmful	 effects	
associated	 with	 the	 organic	 solvents	 and	 is	 environmentally	
benign.	These	reactions	become	more	sophisticated	if	they	can	
be	 performed	 under	 supramolecular	 catalysis.	 In	 view	 of	 the	
above,	 the	 development	 of	 a	 generally	 applicable	 and	
environmentally	 benign	 methodology	 for	 the	 synthesis	 of	
xanthenes	 derivatives	 is	 highly	 desirable.	 While	 developing	
practically	 simple	 biomimetic	 approaches	 through	 the	
supramolecular	 catalysis	 for	 a	 number	 of	 heterocyclic	
derivatives,	to	overcome	some	of	the	limitations	in	the	existing	
methodologies,	we	report	herein	an	aqueous	phase	synthesis	of	
1,8‐dioxooctahydroxanthenes	 from	 1,3‐cyclohexanedione	 and	
aromatic	aldehydes	in	the	presence	of	β‐cyclodextrin	(β‐CD).	
	
2.	Experimental	
	
2.1.	Instrumentation	
	

All	 reactions	 were	 carried	 out	 without	 any	 special	
precautions	in	an	atmosphere	of	air.	Chemicals	were	purchased	
from	Fluka	and	S.	D.	 Fine	Chemicals	 and	directly	used	 for	 the	
synthesis.	 Thin‐layer	 chromatography	 (TLC):	 precoated	 silica	
gel	 plates	 (60	 F254,	 0.2	mm	 layer;	E.	Merck).	 1H	 NMR	 and	 13C	
NMR	 (Avance	 300,	 Innova	 400	MHz	 and	 Brucker	 Gemini	 200	
MHz)	 spectra	 were	 recorded	 in	 CDCl3	 using	 TMS	 as	 internal	
standard.	 Chemical	 shifts	 (δ)	 are	 reported	 in	 ppm,	 and	 spin‐
spin	coupling	constants	(J)	are	in	Hz.	Melting	points	(M.p.)	were	
determined	on	a	Fischer‐Johns	melting	point	apparatus.	IR	and	
MS	 were	 recorded	 on	 a	 Thermo	 Nicolet	 Nexus	 670	 FT‐IR	
spectrometer	 and	 Finnegan	 MAT	 1020	 mass	 spectrometer	
operating	at	70	eV.	



Kokkirala	et	al.	/	European	Journal	of	Chemistry	2	(2)	(2011)	272‐275	 273	
 

 
 

2.2.	Synthesis	
	

General	procedure	for	the	synthesis	of	3,3,6,6,‐tetramethyl‐9‐
phenyl‐3,4,6,7‐tetrahydro‐2H‐xanthene‐1,8(5H,9H)dione	
derivatives	 in	 water:	 β‐cyclodextrin	 (1.135	 g,	 1	 mmol)	 was	
dissolved	 in	water	 (10	mL)	by	warming	 to	60	 oC	until	 a	 clear	
solution	 was	 formed.	 To	 this	 clear	 solution	 aldehyde	 (1.0	
mmol)	was	added	and	the	mixture	stirred	for	10	min,	and	then	
followed	by	the	addition	of	1,3‐diketone	(2.0	mmol).	Then,	the	
mixture	was	heated	at	60‐65	oC	until	completion	of	the	reaction	
as	 indicated	 by	 TLC.	 The	 mixture	 was	 cooled	 to	 room	
temperature	 and	 β‐CD	 was	 filtered,	 the	 aqueous	 phase	 was	
extracted	 with	 ethyl	 acetate	 (3x10	 mL).	 The	 organic	 layers	
were	 washed	 with	 water,	 brine	 solution	 and	 dried	 with	
anhydrous	 Na2SO4.	 The	 combined	 organic	 layers	 were	
evaporated	 under	 reduced	 pressure	 and	 the	 resulting	 crude	
product	was	 purified	 by	 column	 chromatography,	 using	 ethyl	
acetate:hexane	 (2:8)	 as	 eluents	 to	 give	 the	 corresponding	
xanthenes	in	good	to	excellent	yields	(Scheme	1,	Table	1).	
	

 
	

Scheme	1	
	
9‐Phenyl‐3,4,6,7‐tetrahydro‐2H‐xanthene‐1,8(5H,9H)‐dione	

(3a)	(Table	1,	Entry	1):	White	Solid.	Yield:	95%.	M.p.:	269‐270	
oC.	 FT‐IR	 (KBr,	 cm‐1):	 2960,	 2928,	 1592,	 1650,	 1372,	 1159,	
1060,	842,	774,	690.	 1H	NMR	(300	MHz,	CDCl3):	7.10‐7.24	(m,	
5H,	ArH),	5.45	(s,	1H,	CH),	2.60‐2.67	(m,	4H,	2xCH2),	2.25‐2.30	
(m,	4H,	2xCH2),	1.91‐1.99	(m,	2H,	CH2),	1.83‐1.90	(m,	2H,	CH2).	
MS	(ESI,	m/z):	312	[M+NH4]+.	

9‐(4‐Bromophenyl)‐3,4,6,7‐tetrahydro‐2H‐xanthene‐1,8(5H,	
9H)‐dione	(3b)	(Table	1,	Entry	2):	White	Solid.	Yield:	91%.	M.p.:	
284‐285	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 3100,	2980,	 2878,	 1589,	 1490,	
1303,	1158,	890,	709,	660.	1H	NMR	(300	MHz,	CDCl3):	7.21‐7.27	
(m,	4H,	ArH),	5.46	(s,	1H,	CH),	2.60‐2.68	(m,	4H,	2xCH2),	2.26‐
2.31	(m,	4H,	2xCH2),	1.92‐1.98	(m,	2H,	CH2),	1.82‐1.90	(m,	2H,	
CH2).	MS	(ESI,	m/z):	391	[M+NH4]+.	

9‐(3‐Hydroxyphenyl)‐3,4,6,7‐tetrahydro‐2H‐xanthene‐1,8	
(5H,9H)‐dione	(3c)	(Table	1,	Entry	3):	White	Solid.	Yield:	87%.	
M.p.:	 255‐256	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 3250,	 3017,	 2930,	 1655,	
1590,	935,	829,	730,	560.	1H	NMR	(300	MHz,	CDCl3):	7.10‐7.14	
(m,	4H,	ArH),	5.47	(s,	1H,	CH),	2.60‐2.65	(m,	4H,	2×CH2),	2.28‐
2.30	(m,	4H,	2×CH2),	1.91‐1.94	(m,	2H,	CH2),	1.83‐1.88	(m,	2H,	
CH2).	MS	(ESI,	m/z):	328	[M+NH4]+.	

9‐(3‐Chlorophenyl)‐3,4,6,7‐tetrahydro‐2H‐xanthene‐1,8(5H,	
9H)‐dione	(3d)	(Table	1,	Entry	4):	White	Solid.	Yield:	85%.	M.p.:	
275‐276	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 2960,	2868,	 1593,	 1462,	 1374,	
1155,	1051,	870,	790,	675.	1H	NMR	(300	MHz,	CDCl3):	7.09‐7.14	
(m,	4H,	ArH),	5.48	(s,	1H,	CH),	2.61‐2.64	(m,	4H,	2xCH2),	2.28‐
2.30	(m,	4H,	2xCH2),	1.91‐1.94	(m,	2H,	CH2),	1.83‐1.88	(m,	2H,	
CH2).	MS	(ESI,	m/z):	346	[M+NH4]+.	

9‐p‐Tolyl‐3,4,6,7‐tetrahydro‐2H‐xanthene‐1,8(5H,9H)‐dione	
(3e)	(Table	1,	Entry	5):	White	Solid.	Yield:	90%.	M.p.:	262‐264	
oC.	FT‐IR	(KBr,	cm‐1):	2960,	2930,	1592,	1372,	1159,	1041,	842,	
770,	 690.	 1H	 NMR	 (300	MHz,	 CDCl3):	 7.01‐7.08	 (m,	 4H,	 ArH),	
5.45	 (s,	 1H,	 CH),	 2.60‐2.63	 (m,	 4H,	 2xCH2),	 2.24‐2.27	 (m,	 4H,	
2xCH2),	1.91‐1.95	(m,	2H,	CH2),	1.82‐1.85	(m,	2H,	CH2).	MS	(ESI,	
m/z):	326	[M+NH4]+.	

9‐(4‐Chlorophenyl)‐3,4,6,7‐tetrahydro‐2H‐xanthene‐1,8(5H,	
9H)‐dione	(3f)	(Table	1,	Entry	6):	White	Solid.	Yield:	90%.	M.p.:	

288‐289	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 3200,	2960,	 2930,	 1589,	 1305,	
1093,	887,	830,	720,	660.	1H	NMR	(300	MHz,	CDCl3):	7.20	(d,	J	=	
8.5	Hz,	2H,	ArH),	7.25	(d,	J	=	8.5	Hz,	2H,	ArH),	5.45	(s,	1H,	CH),	
2.61‐2.69	 (m,	4H,	2xCH2),	 2.26‐2.32	 (m,	4H,	2xCH2),	 1.93‐1.98	
(m,	 2H,	 CH2),	 1.83‐1.90	 (m,	 2H,	 CH2).	 MS	 (ESI,	 m/z):	 346	
[M+NH4]+.	

9‐(4‐Hydroxyphenyl)‐3,4,6,7‐tetrahydro‐2H‐xanthene‐1,8	
(5H,9H)‐dione	(3g)	(Table	1,	Entry	7):	White	Solid.	Yield:	90%.	
M.p.:	 245‐246	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 3295,	 3017,	 2929,	 1655,	
1590,	930,	835,	750,	585.	1H	NMR	(300	MHz,	CDCl3):	7.10	(d,	J	=	
8.3	Hz,	2H,	ArH),	6.78	(d,	J	=	8.3	Hz,	2H,	ArH),	5.46	(s,	1H,	CH),	
2.61‐2.65	 (m,	4H,	2xCH2),	 2.25‐2.30	 (m,	4H,	2xCH2),	 1.92‐1.96	
(m,	 2H,	 CH2),	 1.83‐1.89	 (m,	 2H,	 CH2).	 MS	 (ESI,	 m/z):	 328	
[M+NH4]+.	

9‐(4‐Fluorophenyl)‐3,4,6,7‐tetrahydro‐2H‐xanthene‐1,8(5H,	
9H)‐dione	(3h)	(Table	1,	Entry	8):	White	Solid.	Yield:	88%.	M.p.:	
275‐276	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 3200	 2970,	 2935,	 1593,	 1372,	
1228,	 1068,	 870,	 835,	 750,	 669.	 1H	 NMR	 (300	 MHz,	 CDCl3):	
7.20‐7.28	 (m,	 4H,	 ArH),	 5.45	 (s,	 1H,	 CH),	 2.60‐2.66	 (m,	 4H,	
2xCH2),	2.26‐2.30	(m,	4H,	2xCH2),	1.92‐1.96	(m,	2H,	CH2),	1.84‐
1.90	(m,	2H,	CH2).	MS	(ESI,	m/z):	330	[M+NH4]+.	

9‐(4‐Nitrophenyl)‐3,4,6,7‐tetrahydro‐2H‐xanthene‐1,8(5H,	
9H)‐dione	(3i)	(Table	1,	Entry	9):	White	Solid.	Yield:	80%.	M.p.:	
265‐266	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 3200,	2960,	 2928,	 1592,	 1390,	
1550,	 1159,	 1040,	 842,	 774,	 690.	 1H	 NMR	 (300	MHz,	 CDCl3):	
7.99	(d,	J	=	8.2	Hz,	2H,	ArH),	7.45	(d,	J	=	8.5	Hz,	2H,	ArH),	5.46	(s,	
1H,	 CH),	 2.59‐2.69	 (m,	 4H,	 2xCH2),	 2.24‐2.32	 (m,	 4H,	 2xCH2),	
1.93‐1.99	(m,	2H,	CH2),	1.82‐1.90	(m,	2H,	CH2).	MS	(ESI,	m/z):	
357	[M+NH4]+.	

3,3,6,6‐Tetramethyl‐9‐phenyl‐3,4,6,7‐tetrahydro‐2H‐xant‐
hene‐1,8(5H,	 9H)dione	 (3j)	 (Table	 1,	 Entry	 10):	 White	 Solid.	
Yield:	 96%.	 M.p.:	 203‐205	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 2962,	 2928,	
1592,	 1372,	 1159,	 1041,	 842,	 774,	 692.	 1H	 NMR	 (300	 MHz,	
CDCl3):	 7.24‐7.19	 (m,	 2H,	 ArH),	 7.14‐7.09	 (m,	 1H,	 ArH),	 7.04‐
7.01	(d,	J	=	7.93	Hz,	2H,	ArH),	5.47	(s,	1H,	CH),	2.47‐2.25	(m,	8H,	
4xCH2),	 1.25	 (s,	 6H,	 2xCH3),	 1.11	 (s,	 6H,	 2xCH3).	 13C	NMR	 (75	
MHz,	 CDCl3):	 190.3,	 189.3,	 137.9,	 128.1,	 126.7,	 125.7,	 115.4,	
46.9,	46.4,	32.6,	31.3,	29.6,	27.3.	MS	(ESI,	m/z):	369	[M+NH4]+.	

9‐(3‐Hydroxyphenyl)‐3,3,6,6‐tetramethyl‐3,4,6,7‐tetrahydro‐
2H‐xanthene‐1,8(5H,	9H)dione	 (3k)	 (Table	1,	Entry	11):	White	
Solid.	 Yield:	 86%.	 M.p.:	 215‐216	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 3296,	
3017,	2929,	1655,	1592,	930,	829,	755,	590.	1H	NMR	(300	MHz,	
CDCl3):	7.25‐7.10	(m,	2H,	ArH),	7.01	(s,	1H,	ArH),	6.92‐6.90	(d,	J	
=	7.17	Hz,	1H,	ArH),	5.41	(s,	1H,	CH),	2.47‐2.26	(m,	8H,	4xCH2),	
1.25	 (s,	 6H,	 2xCH3),	 1.11	 (s,	 6H,	 2xCH3).	 13C	 NMR	 (75	 MHz,	
CDCl3):	 190.6,	 189.6,	 155.7,	 139.9,	 129.1,	 118.8,	 115.4,	 114.1,	
112.9,	 46.9,	 46.2,	 32.5,	 31.3,	 29.6,	 27.3.	 MS	 (ESI,	 m/z):	 385	
[M+NH4]+.	

9‐(3‐Chlorophenyl)‐3,3,6,6‐tetramethyl‐3,4,6,7‐tetrahydro‐
2H‐xanthene‐1,8(5H,	 9H)dione	 (3l)	 (Table	 1,	 Entry	 12):	White	
Solid.	 Yield:	 88%.	 M.p.:	 183‐184	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 2958,	
2868,	 1593,	 1462,	 1374,	 1155,	 870,	 788,	 674.	 1H	 NMR	 (300	
MHz,	 CDCl3):	 7.28‐7.12	 (m,	 2H,	 ArH),	 7.01	 (s,	 1H,	 ArH),	 6.92‐
6.91	(d,	J	=	7.17	Hz,	1H,	ArH),	5.40	(s,	1H,	CH),	2.47‐2.26	(m,	8H,	
4xCH2),	 1.25	 (s,	 6H,	 2xCH3),	 1.11	 (s,	 6H,	 2xCH3).	 13C	NMR	 (75	
MHz,	 CDCl3):	 190.5,	 189.3,	 140.3,	 134.1,	 129.3,	 127.1,	 125.9,	
124.8,	 115.0,	 46.9,	 46.3,	 32.5,	 31.4,	 29.5,	 27.3.	MS	 (ESI,	m/z):	
403	[M+NH4]+.	

9‐(4‐Bromophenyl)‐3,3,6,6‐tetramethyl‐3,4,6,7‐tetrahydro‐
2H‐xanthene‐1,8(5H,	9H)dione	(3m)	(Table	1,	Entry	13):	White	
Solid.	 Yield:	 89%.	 M.p.:	 240‐241	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 2959,	
2878,	 1589,	 1484,	 1303,	 1158,	 888,	 709,	 664.	 1H	 NMR	 (300	
MHz,	CDCl3):	7.36‐7.33	(d,	J	=	7.58	Hz,	2H,	ArH),	6.92‐6.89	(d,	J	=	
7.58	Hz,	 2H,	ArH),	 5.39	 (s,	 1H,	 CH),	 2.46‐2.25	 (m,	 8H,	 4xCH2),	
1.22	 (s,	 6H,	 2xCH3),	 1.11	 (s,	 6H,	 2xCH3).	 13C	 NMR	 (75	 MHz,	
CDCl3):	 190.5,	 189.3,	 137.2,	 131.2,	 128.5,	 119.5,	 115.1,	 46.9,	
46.3,	32.4,	31.3,	29.5,	27.3.	MS	(ESI,	m/z):	447	[M+NH4]+.	

	
	



274	 Kokkirala	et	al.	/	European	Journal	of	Chemistry	2	(2)	(2011)	272‐275	
	

	
Table	1.	Synthesis	of	1,8‐dioxooctahydroxanthene	derivatives	catalyzed	by	β‐cyclodextrina.	
Entry	 Aldehyde	 1,3	dicarbonyl	compound Product Yieldb (%) M.p.	(oC)	 Reference

Found Reported Found	 Reported	
1	 Benzaldehyde	 1,3‐Cyclohexanedione 3a 95 82 269‐270	 270‐271	 [33]
2	 p‐Bromo	benzaldehyde	 1,3‐Cyclohexanedione 3b 91 93 284‐285	 284‐285	 [33]
3	 m‐Hydroxy	benzaldehyde	 1,3‐Cyclohexanedione 3c 87 89 255‐256	 255‐257	 [33]
4	 m‐Chloro	benzaldehyde	 1,3‐Cyclohexanedione 3d 85 86 275‐276	 276‐277	 [16]
5	 p‐Methyl	benzaldehyde	 1,3‐Cyclohexanedione 3e 90 87 262‐264	 262‐263	 [16]
6	 p‐Chloro	benzaldehyde	 1,3‐Cyclohexanedione 3f 90 92 288‐289	 289‐290	 [33]
7	 p‐Hydroxy	benzaldehyde	 1,3‐Cyclohexanedione 3g 90 75 245‐246	 245‐247	 [26]
8	 p‐Fluoro	benzaldehyde	 1,3‐Cyclohexanedione 3h 88 90 275‐276	 275‐277	 [35]
9	 p‐Nitro	benzaldehyde	 1,3‐Cyclohexanedione 3i 80 93 265‐266	 265‐267	 [33]
10	 Benzaldehyde	 5,5‐Dimethyl	1,3‐Cyclohexanedione 3j 96 89 203‐205	 204‐205	 [17]
11	 m‐Hydroxy	benzaldehyde	 5,5‐Dimethyl	1,3‐Cyclohexanedione 3k 86 70.5 215‐216	 215‐218	 [28]
12	 m‐Chloro	benzaldehyde	 5,5‐Dimethyl	1,3‐Cyclohexanedione 3l 88 94 183‐184	 184‐186	 [17]
13	 p‐Bromo	benzaldehyde	 5,5‐Dimethyl	1,3‐Cyclohexanedione 3m 89 84.5 240‐241	 240‐242	 [28]
14	 p‐Fluoro	benzaldehyde	 5,5‐Dimethyl	1,3‐Cyclohexanedione 3n 89 92 223‐224	 223‐225	 [35]
15	 p‐Chloro	benzaldehyde	 5,5‐Dimethyl	1,3‐Cyclohexanedione 3o 90 92 230‐232	 230‐232	 [17]
16	 Cinnamaldehyde	 5,5‐Dimethyl	1,3‐Cyclohexanedione 3p 85 90 175‐177	 175‐177	 [17]
a	Reaction	conditions:	1,3‐	diketone	(2.0	mmol),	aromatic	aldehyde	(1.0	mmol),	β‐CD	(1.0	mmol),	water	(10	mL),	60‐65	oC,	10‐12	h.		
b	Yields	of	the	isolated	product.	

	
	
9‐(4‐Fluorophenyl)‐3,3,6,6‐tetramethyl‐3,4,6,7‐tetrahydro‐

2H‐xanthene‐1,8(5H,	9H)dione	 (3n)	 (Table	1,	Entry	14):	White	
Solid.	 Yield:	 89%.	 M.p.:	 223‐224	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 2962,	
2930,	 1593,	 1372,	 1228,	 1065,	 869,	 833,	 753,	 660.	 1H	 NMR	
(300	 MHz,	 CDCl3):	 7.01‐6.88	 (m,	 4H,	 ArH),	 5.41	 (s,	 1H,	 CH),	
2.46‐	 2.25	 (m,	 8H,	 4xCH2),	 1.23	 (s,	 6H,	 2xCH3),	 1.11	 (s,	 6H,	
2xCH3).	 13C	NMR	 (75	MHz,	 CDCl3):	 190.4,	 189.3,	 162.5,	 159.3,	
133.5,	 128.2,	 128.1,	 115.4,	 115.0,	 114.7,	 46.9,	 46.3,	 32.1,	 31.3,	
29.5,	27.3.	MS	(ESI,	m/z):	387	[M+NH4]+.	

9‐(4‐Chlorophenyl)‐3,3,6,6‐tetramethyl‐3,4,6,7‐tetrahydro‐
2H‐xanthene‐1,8(5H,	9H)dione	 (3o)	 (Table	1,	 Entry	15):	White	
Solid.	 Yield:	 90%.	 M.p.:	 230‐232	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 2960,	
2929,	1589,	1305,	1093,	887,	833,	720,	658.	1H	NMR	(300	MHz,	
CDCl3):	 7.25‐7.18	 (m,	 2H,	 ArH),	 6.97‐6.95	 (d,	 J	 =	 8.12	 Hz,	 2H,	
ArH),	 5.40	 (s,	 1H,	 CH),	 2.46‐2.25	 (m,	 8H,	 4xCH2),	 1.22	 (s,	 6H,	
2xCH3),	 1.11	 (s,	 6H,	 2xCH3).	 13C	NMR	 (75	MHz,	 CDCl3):	 190.5,	
189.3,	136.6,	131.4,	115.2,	46.9,	46.3,	32.3,	31.3,	29.5,	27.3.	MS	
(ESI,	m/z):	403	[M+NH4]+.	

(E)‐3,3,6,6‐Tetramethyl‐9‐styryl‐3,4,6,7‐tetrahydro‐2H‐
xanthene‐1,8(5H,9H)‐dione	 (3p)	 (Table	 1,	 Entry	 16):	 White	
Solid.	 Yield:	 85%.	 M.p.:	 175‐177	 oC.	 FT‐IR	 (KBr,	 cm‐1):	 2962,	
2928,	 1665,	 1610,	 1592,	 1372,	 1159,	 1041,	 842,	 774,	 700.	 1H	
NMR	(300	MHz,	CDCl3):	7.28‐7.19	(m,	5H,	ArH),	6.24	–	6.34	(m,	
2H,	‐CH=CH),	5.42	(s,	1H,	CH),	2.46‐2.26	(m,	8H,	4xCH2),	1.25	(s,	
6H,	 2xCH3),	 1.11	 (s,	 6H,	 2xCH3).	 13C	 NMR	 (75	 MHz,	 CDCl3):	
190.9,	163.2,	137.4,	131.2,	128.9,	127.6,	125.9,	115.2,	48.9,	42.9,	
32.6,	31.0,	28.3,	27.9.	MS	(ESI,	m/z):	394	[M+NH4]+.	
	
3.	Results	and	discussion		
	

Cyclodextrins	 are	 cyclic	 oligosaccharides	 which	 have	
generated	 interest	 as	 enzyme	 models,	 due	 to	 their	 ability	 to	
bind	substrates	selectively	and	catalyze	chemical	reactions,	by	
supramolecular	 catalysis	 [36‐46],	 involving	 the	 reversible	
formation	 of	 host‐guest	 complexes	 with	 a	 broad	 range	 of	
substrates	 by	 non	 covalent	 bonding,	 as	 seen	 in	 enzyme	
complexation	 processes.	We	 describe,	 here	 in	 the	 remarkable	
catalytic	activity	of	β‐CD	in	the	reaction	of	aromatic	aldehydes	
and	 1,3‐cyclohexanedione	 to	 give	 exclusively	 substituted	 1,8‐
dioxooctahydroxanthenes	 (Scheme	1).	 In	general,	 the	 reaction	
was	 carried	 out	 by	 the	 addition	 of	 benzaldehyde	 to	 β‐CD,	
dissolved	 in	 water.	 To	 this	 aqueous	 solution	 of	 the	 β‐CD‐
benzaldehyde	 complex,	 1,3‐cyclohexanedione	 was	 added	 by	
stirring	 the	 mixture	 at	 60‐65	 oC	 to	 give	 the	 corresponding	
xanthene	 in	 high	 yield.	 To	 study	 the	 scope	 of	 this	 reaction,	
various	aromatic	aldehydes	were	subjected	to	this	protocol.	All	
the	 reactions	 have	 proceeded	 efficiently	 and	 produced	 high	
yields	 without	 formation	 of	 any	 side	 products.	 This	 can	 be	
concluded	 that	 the	 activation	 of	 aldehyde	 by	 the	 hydrogen	
bonding	 interactions	of	β‐CD	contribute	 for	 the	process	of	 the	

reaction	 to	 prove	 the	 role	 of	 cyclodextrin,	 NMR	 studies	 were	
carried	 out	 on	 β‐CD	 and	 the	 β‐CD‐benzaldehyde	 inclusion	
complex.	It	was	observed	from	spectral	studies,	there	is	an	up	
field	 shift	 of	 H‐C	 (3)	 (0.017	 ppm)	 and	 H‐C	 (5)	 (0.07	 ppm)	
protons	of	CD	in	the	β‐CD‐benzaldehyde	complex	as	compared	
to	β‐cyclodextrin,	 indicating	 that	 the	 reaction	was	 proceeding	
through	a	host‐guest	complexation	phenomenon.	The	hydrogen	
bonding	 interactions	 activate	 aldehyde	 molecule,	 involved	 in	
host‐guest	complexation	in	β‐CD	cavity,	which	in	turn	facilitates	
the	 bonding	 with	 tautomeric	 form	 of	 1,3‐cyclohexanedione	
moiety,	stabilised	by	the	primary	and	secondary	‐OH	groups	of	
β‐CD,	 which	 further	 reacts	 with	 another	 molecule	 of	 1,3‐
cyclohexanedione,	 ultimately	 leading	 to	 1,8‐
dioxooctahydroxanthene	as	a	cyclised	product	in	the	process	of	
this	 reaction.	 No	 product	 formation	 was	 observed	 in	 the	
absence	 of	 cyclodextrin.	 All	 products	 were	 characterized	 by	
their	 m.p.,	 1H‐NMR,	 13C‐NMR,	 IR,	 and	MS	 and	 compared	with	
the	 known	 compounds.	 After	 completion	 of	 the	 reaction,	 the	
aqueous	 layer	was	cooled	 to	room	temperature	and	β‐CD	was	
filtered	 and	 washed	 with	 ice‐cooled	 water	 and	 dried.	 The	
recovered	 β‐cyclodextrin	 was	 further	 used	 with	 the	 same	
substrates	as	a	catalyst	and	checked	for	the	yields	and	catalytic	
activity	of	recovered	catalyst	 (β‐CD).	As	shown	 in	Table	2,	 the	
yields	 of	 1,8‐dioxooctahydroxanthene	 after	 two	 (or)	 three	
cycles	were	almost	the	same.		
	
Table	2.	 Synthesis	 of	 1,8‐dioxooctahydroxanthene	 derivatives	 catalyzed	 by	
β‐cyclodextrina.	
Recycles Yieldb (%) ‐CD	recovery	(%)	
1 95 95	
2 92 94	
3 89 90	
4 88 89	
a	 Reaction	 conditions:	 1,3‐	 diketone	 (2.0	 mmol),	 aromatic	 aldehyde	 (1.0	
mmol),	β‐CD	(1.0	mmol),	water	(10	mL),	60‐65	oC,	10‐12	h.	
b	Yields	of	the	isolated	product.	

	
4.	Conclusion	
	

In	 conclusion,	 we	 have	 developed	 a	 simple	 and	 efficient	
aqueous	 phase	 synthesis	 of	 various	 1,8‐dioxooctahydro	
xanthenes	 by	 the	 reaction	 of	 the	 corresponding	 1,3‐
cyclohexanedione	 with	 aromatic	 aldehydes	 under	
environmentally	 benign	 conditions	 in	 the	 presence	 of																			
β‐cyclodextrin.	 These	 cyclodextrin	 mediated	 aqueous	 phase	
organic	 reactions	 are	 useful	 both	 from	 economical	 and	
environmental	 points	 of	 view.	 This	 methodology	 also	
overcomes	the	formation	of	unwanted	by‐products,	low	yields,	
and	use	of	hazardous	solvents	and	high	temperatures.	

	
	
	



Kokkirala	et	al.	/	European	Journal	of	Chemistry	2	(2)	(2011)	272‐275	 275	
 

 
 

Acknowledgement	
	
We	 are	 grateful	 to	 University	 Grants	 Commission	 (UGC),	

New	Delhi,	 for	the	research	fellowships	to	K.	S.	and	Council	of	
Scientific	and	Industrial	Research	(CSIR),	New	Delhi,	for	S.	N.	M.	
	
References	
	
[1]. Hideo,	T.	(1981)	Jpn	Tokkyo	Koho	JP	56005480.	
[2]. Poupelin,	J.	P.;	Saint‐Ruf,	G.;	Foussard‐Blanpin,	O.;	Narcisse,	G.;	Uchida	

Ernouf,	G.;	Lacroix,	R.	Eur.	J.	Med.	Chem.	1978,	13,	67‐75.	
[3]. Lambert,	R.	W.;	Martin,	J.	A.;	Merrett,	J.	H.;	Parkes,	K.	E.	B.;	Thomas,	G.	

J.	1997,	PCT	Int.	Appl.	WO9706178.	
[4]. Ion,	R.	M.;	Planner,	A.;	Wiktorowicz,	K.;	Frackowiak.	D.	Acta	Biochim.	

Pol.	1998,	45,	833‐845.		
[5]. Hatakeyma,	 S.;	 Ochi,	 N.;	 Numata,	 H.;	 Takano,	 S.	 J.	 Chem.	 Soc.	 Chem.	

Commun.	1988,	1202‐1204.	
[6]. Hilderbrand,	 S.	 A.;	Weissleder,	 R.	Tetrahedron	Lett.	2007,	48,	 4383‐

4385.		
[7]. Menchen,	 S.	 M.;	 Benson,	 S.	 C.;	 Lam,	 J.	 Y.	 L.;	 Zhen,	 W.;	 Sun,	 D.;	

Rosenblum,	B.	B.;	Kha,	S.	H.;	Taing,	M.	US	Patent,	2003,	6,583,	168.		
[8]. Banerjee,	A.;	Mukherjee,	A.	K.	Stain	Technol.	1981,	56,	83‐85.		
[9]. Reynolds,	 G.	 A.;	 Tuccio,	 S.	 A.;	 Peterson,	 O.	 G.;	 Specht,	 D.	 P.	 German	

Patent,	1971,	DE2109040.		
[10]. Horning,	E.	C.;	Horning,	M.	G.	J.	Org.	Chem.	1946,	11,	95‐99.	
[11]. Wang,	J.	Q.;	Harvey,	R.	G.	Tetrahedron	2002,	58,	5927‐5931.	
[12]. Casiraghi,	G.;	Casnati,	G.;	Cornia,	M.	Tetrahedron	Lett.	1973,	14,	679‐

682.		
[13]. Casiraghi,	G.;	Casnati,	G.;	Catellani,	M.;	Cornia,	M.	Synthesis	1974,	564‐

564.	
[14]. Jin,	T.	S.;	 Zhang,	 J.	 S.;	Wang,	A.	Q.;	 Li,	T.	 S.	Synth.	Commun.	2005,	35,	

2339‐2345.	
[15]. Hua,	G.	P.;	Li,	T.	J.;	Zhu,	S.	L.;	Zhang,	X.	J.	Chin.	J.	Org.	Chem.	2005,	25(6),	

716‐719.	
[16]. Jin,	T.	S.;	Qi,	N.;	Li,	M.;	Han,	L.	S.;	Liu,	L.	B.;	Li,	T.	S.	Asian.	J.	Chem.	2007,	

19,	3803‐3809.	
[17]. Jin,	T.	S.;	Zhang,	J.	S.;	Xio,	J.C.;	Wang,	A.	Q.;	Li,	T.	S.	Synlett.	2004,	5,	866‐

870.		
[18]. Khosropour,	 A.	 R.;	 Khodaei,	 M.	M.;	 Moghannian,	 H.	 Synlett.	2005,	 6,	

955‐958.	
[19]. Das,	B.;	Thirupathi,	P.;	Ravinder	Reddy,	K.;	Ravikanth,	B.;	Nagarapu,	L.	

Catal.	Commun.	2007,	8,	535‐538.	
[20]. Das,	 B.;	 Thirupathi,	 P.;	 Mahender,	 I.;	 Reddy,	 V.	 S.;	 Rao.	 Y.	 K.;	 J.	Mol.	

Catal.	A:	Chem.	2006,	247,	233‐239.	
[21]. Shakibaei,	 G.	 I.;	Mirzaei,	 P.;	 Bazgir,	 A.	Appl.	Catal.	A:	Gen.	2007,	325,	

188‐192.	
[22]. Dabiri,	M.;	Azimi,	S.	C.;	Bazgir,	A.	Chem.	Pap.	2008,	62,	522‐526.	
[23]. Zhang,	Z.	H.;	Tao,	X.	Y.	Aus.	J.	Chem.	2008,	61,	77‐79.	
[24]. Li,	 J.	 J.;	 Tao,	 X.	 Y.;	 Zhang,	 Z.	 H.	Phosphorus	 Sulfur.	2008,	 183,	 1672‐

1678.	
[25]. Song,	G.;	Wang,	B.;	Luo,	H.;	Yang,	L.	Catal.	Commun.	2007,	8,	673‐676.	
[26]. John,	A.;	Yadav,	P.;	 J.	 P.;	Palaniappan,	 S.	 J.	Mol.	Catal.	A:	Chem.	2006,	

248,	121‐125.	
[27]. Srihari,	P.;	Mandal,	S.S.;	Reddy,	J.S.S.;	Rao,	R.	S.;	Yadav,	J.S.	Chin.	Chem.	

Lett.	2008,	19,	771‐774.	
[28]. Kantevari,	S.;	Bantu,	R.;	Nagarapu,	L.	J.	Mol.	Catal	A:	Chem.	2007,	269,	

53‐57.	
[29]. Lu,	H.	Y.;	Li,	J.	J.;	Zhang,	Z.	H.	Appl.	Organometal.	Chem.	2009,	23,	165‐

169.	
[30]. Karthikeyana,	G.;	Pandurangana,	A.	 J.	Mol.	Catal.	A:	Chem.	2009,	311,	

36‐45.	
[31]. Kumar,	D.;	Sandhu,	J.	S.	Synth.	Commun.	2010,	40,	510‐517.	
[32]. Li,	J.;	Lu,	L.;	Su,	W.	Tetrahedron	Lett.	2010,	51,	2434‐2437.	
[33]. Kang,	H.;	Hu,	Y.;	Huang,	H.;	Wei,	P.	Heterocycl.	Commun.	2008,	14,	223‐

227.		
[34]. Ma,	J.	 J.;	Wang,	C.;	Wu,	Q.	H.;	Tang,	R.	X.;	Liu,	H.	Y.;	Li,	Q.	Heteroatom.	

Chem.	2008,	19,	609‐611.		
[35]. Fang,	D.;	Gong,	K.;	Liu,	Z.	L.	Catal.	Lett.	2009,	127,	291‐295.	
[36]. Narender,	M.;	Reddy,	M.	S.;	 Sridhar,	R.;	Nageswar,	Y.	V.	D.;	Rao,	K.	R.	

Tetrahedron	Lett.	2005,	46,	5953‐5955.	
[37]. Reddy,	M.	S.;	Narender,	M.;	Nageswar,	Y.	V.	D.;	Rao,	K.	R.	Tetrahedron	

Lett.	2005,	46,	6437‐6439.	
[38]. Sridhar,	R.;	Srinivas,	B.;	Kumar,	V.	P.;	Reddy,	V.	P.;	Kumar,	A.	V.;	Rao,	K.	

R.	Adv.	Synth.	Catal.	2008,	350,	1489‐1492.	
[39]. Madhav,	B.;	Murthy,	S.	N.;	Reddy,	V.	P.;	Rao,	K.	R.;	Nageswar,	Y.	V.	D.	

Tetrahedron	Lett.	2009,	50,	6025‐6028.	
[40]. Murthy,	S.	N.;	Madhav,	B.;	Kumar,	A.	V.;	Rao,	K.	R.;	Nageswar,	Y.	V.	D.	

Tetrahedron	2009,	65,	5251‐5256.	
[41]. Murthy,	S.	N.;	Madhav,	B.;	Reddy,	V.	P.;	Nageswar,	Y.	V.	D.	Tetrahedron	

Lett.	2010,	51,	3649‐3653.		
[42]. Shankar,	 J.;	Karnakar,	K.;	Srinivas,	B.;	Nageswar,	Y.	V.	D.	Tetrahedron	

Lett.	2010,	51,	3938‐3939.		

[43]. Kirschner,	D.;	Jaramillo,	M.;	Green,	T.;	Hapiot,	F.;	Leclercq,	L.;	Bricout,	
H.;	Monflier,	E.	J.	Mol.	Catal.	A:	Chem.	2008,	286,	11‐20.		

[44]. Legrand,	F.	X.;	Sauthier,	M.;	Flahaut,	C.;	Hachani,	J.;	Elfakir,	C.;	
Fourmentin,	S.;	Tilloy,	S.;	Monflier,	E.	J.	Mol.	Catal.	A:	Chem.	2009,	300,	
72‐77.		

[45]. Six,	N.;	Menuel,	S.;	Bricout,	H.;	Hapiot,	F.;	Monflier,	E.	Adv.	Synth.	Catal.	
2010,	352,	1467‐1475.	

[46]. Bricout,	 H.;	 Hapiot,	 F.;	 Ponchel,	 A.;	 Tilloy,	 S.;	 Monflier,	 E.	 Curr.	 Org.	
Chem.	2010,	14,	1296‐1307.