Molecular iodine: An efficient and environment friendly catalyst for the synthesis of 3,5-bis-(arylmethylidene)-tetrahydropyran-4-ones

Article abstract of DOI:10.1080/00397910903531748

A rapid, efficient, convenient and cost-effective procedure has been developed for the synthesis of 3,5-bis-(arylmethylidene)-tetrahydropyran-4-ones by the condensation of tetrahydropyran-4-one with araldehydes in the presence of catalytic amount of iodin

Full text of DOI:10.1080/00397910903531748

This article was downloaded by: [University of Stellenbosch]
On: 08 July 2013, At: 02:22
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Molecular Iodine: An Efficient and
Environment Friendly Catalyst for the
Synthesis of 3,5-Bis-(arylmethylidene)-
tetrahydropyran-4-ones
M. B. Madhusdana Reddy a , Aatika Nizam a & M. A. Pasha a
a Department of Studies in Chemistry, Central College Campus,
Bangalore University, Bengaluru, India
Published online: 09 Nov 2010.
To cite this article: M. B. Madhusdana Reddy , Aatika Nizam & M. A. Pasha (2010) Molecular Iodine:
An Efficient and Environment Friendly Catalyst for the Synthesis of 3,5-Bis-(arylmethylidene)-
tetrahydropyran-4-ones, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 40:24, 3728-3733, DOI: 10.1080/00397910903531748
To link to this article: http://dx.doi.org/10.1080/00397910903531748
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Synthetic Communications1, 40: 3728–3733, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903531748
MOLECULAR IODINE: AN EFFICIENT AND
ENVIRONMENT FRIENDLY CATALYST FOR THE
SYNTHESIS OF 3,5-BIS-(ARYLMETHYLIDENE)-
TETRAHYDROPYRAN-4-ONES
M. B. Madhusdana Reddy, Aatika Nizam, and
M. A. Pasha
Department of Studies in Chemistry, Central College Campus,
Bangalore University, Bengaluru, India
A rapid, efficient, convenient and cost-effective procedure has been developed for the
synthesis of 3,5-bis-(arylmethylidene)-tetrahydropyran-4-ones by the condensation of
tetrahydropyran-4-one with araldehydes in the presence of catalytic amount of iodine
to obtain the products in good to excellent yield. The reactions work at 25 ꢀC and go to
completion within 30–60 min.
Keywords: Araldehydes; 3,5-bis-(arylmethylidene)-tetrahydropyran-4-ones; iodine; tetrahydropyran-4-one
INTRODUCTION
3,5-Bis-(arylmethylidene)-tetrahydropyran-4-ones are very important group of
heterocycles that have many applications in both pharmaceutical and industrial
research. They are also used widely in bioorganic applications,[1] and as useful and
key precursors in the synthesis of a number of heterocyclic compounds.[2] On the
other hand, only a few methods are available in the literature for the synthesis of
these bioactive molecules. The important methods include the reaction of
tetrahydropyran-4-one or tetrahydrothiopyran-4-one with substituted benzalde-
hydes in the presence of catalysts such as Ba(OH)2 in MeOH,[3] a mixture of
MgBr2 Á OEt2 and Et3N in MeOH,[4] LiClO4-TMSNEt2,[5] HCl in AcOH,[6] and a
mixture of LiBr-Et3N in CH2Cl2.[7] However, many of these methods suffer draw-
backs such as: i) Low yield of the products; ii) Require additional reagent; and
iii) Take long duration for completion of the reaction.
Molecular iodine has also received considerable attention in organic synthesis
as an inexpensive, easily available and environmentally benign catalyst for effecting
various organic transformations.[8] In continuation of our research program on
effective utilization of simple and readily available reagents for various organic
Received August 28, 2009.
Address correspondence to Professor Mohamed Pasha, Department of Chemistry, Central College
Campus, Bangalore University, Bangalore 560001, India. E-mail: m_af_pasha@ymail.com or mafpasha@
gmail.com
3728

SYNTHESIS OF 3,5-BIS-(ARYLMETHYLIDENE)-PYRAN-4-ONES
3729
Scheme 1. 3,5-Bis-(arylmethylidene)-tetrahydropyran-4-ones synthesis from araldehydes and
tetrahydropyran-4-one.
transformations and for the synthesis of biologically important compounds. We in
this paper, describe our finding on the formation of 3,5-bis-(arylmethylidene)-
tetrahydropyran-4-ones via a double condensation reaction of araldehydes with
tetrahydropyran-4-one in the presence of catalytic amount of Iodine at room tem-
perature to get good to excellent yield of the desired products (3, Scheme 1).
Recently, we from our laboratory, have reported procedures wherein molecular
iodine has been utilized as an efficient catalyst for the synthesis of azalactones,[9a]
b-acetamido-b-aryl-propiophenones[9b] and xanthenes.[9c]
RESULTS AND DISCUSSION
As a preliminary study, we treated p-anisaldehyde (10 mmol) with tetrahydro-
pyran-4-one (5 mmol) and catalytic iodine to get 3,5-bis-(4-methoxybenzylidene)-
tetrahydropyran-4-one in DCM. To optimize the amount of iodine required for
the catalytic activity 2 mmol, 1 mmol, 0.5 mmol and 0.1 mmol of iodine was
employed for the purpose, and the best result was obtained with 0.1 mmol of iodine
in terms of yield and reaction duration at 25 ꢀC (95%, 60 min).
In the absence of iodine, the reaction did not proceed. We next investigated the
scope and generality of the reaction in which 3,5-bis-(arylmethylidene)-tetrahydro-
pyran-4-ones (3a–3h, Table 1) were successfully prepared in high yield using various
substituted araldehydes. In all cases, the reactions proceed rapidly and go to com-
pletion within 30–60 min at 25 ꢀC.
MECHANISM
A plausible mechanism for the formation of 3,5-bis-(arylmethylidene)-tetrahy-
dropyran-4-ones has been envisaged in Scheme 2. It is assumed that, araldehyde gets
activated in the presence of iodine in the first step of the reaction. In the subsequent
step condensation of the activated araldehyde with tetrahydropyran-4-one [which
may exist in the enolic form] takes place to give 6, followed by elimination of a mol-
ecule of water to give the monoarylmethylidene intermediate 7 (not isolated). 7 may
react with another molecule of activate araldehyde in the next step to give the pro-
duct 3 as shown in Scheme 2.
EXPERIMENTAL
All reagents were commercial and used without further purification. The pro-
ducts were characterized by IR, 1H NMR, 13C NMR, and LC-MS spectral analyses.
The IR and NMR spectra of the products were recorded on Shimadzu FT-IR-8400s

3730
M. B. M. REDDY, A. NIZAM, AND M. A. PASHA
Table 1. Synthesis of 3,5-bis-(arylmethylidene)-tetrahydropyran-4-ones from tetrahydropyran-4-one and
araldehydes
Time
(min)
Yield
(%)b
Mp
(ꢀC)=lit.[5]
Entry
Aldehyde (1)
Product (3)a
3a
30
50
60
98
90
95
186=185–187
109–110=110
180=175–177
3b
3c
3d
3e
3f
55
60
50
85
92
93
169=168–170
205=206–208
190=192–194
3g
3h
55
60
93
89
173=170–172
196=195–197
aAll the products are known and are characterized by IR (entries 3a–3h), 1HNMR (entries 3a–3d and
3g), LC-mass (entries 3a–3d) spectral analysis from Mp’s (entries 3a–3h) and comparison with the samples
prepared by reported method [Ref 5].
bIsolated yields.
and Bruker AMX 200-MHz spectrophotometers respectively. LC-MS was
performed on an Agilent Technologies 1200 series instrument.
Typical Procedure for the Preparation of 3,5-Bis-
(arylmethylidene)-tetrahydropyran-4-ones
A mixture of tetrhydrpyran-4-one (1, 5 mmol), araldehyde (2, 10 mmol) in
DCM (20 ml) was stirred at 25 ꢀC in the presence of iodine (0.1 mmol) for an

SYNTHESIS OF 3,5-BIS-(ARYLMETHYLIDENE)-PYRAN-4-ONES
3731
Scheme 2. A plausible mechanism for the formation of 3,5-bis-(arylmethylidene)-tetrahydropyran-
4-ones.
appropriate time (Table 1). The course of the reaction was monitored by TLC (15%
ethyl acetate in light petrol). At the end of the reaction, a syrupy liquid was obtained
which when allowed to stand at room temperature for 30 min gave a solid. The solid
so obtained was washed with saturated Na2S2O3 solution and dried over anhydrous
MgSO4 to get the crude product. The crude was subjected to purification by recrys-
tallization from ethyl acetate.
CONCLUSION
In conclusion a rapid, efficient and cost-effective procedure has been developed
for the synthesis of 3,5-bis-(arylmethylidene)-tetrahydropyran-4-ones. The procedure
is simpler and faster than the protocols published to date. It is also consistent with a
green chemistry approach since no heating or additional equipment is required. The
catalyst used is inexpensive, non-toxic, non-corrosive and readily available chemical
that is commonly found in most organic chemistry laboratories. The simplicity,
together with the use of inexpensive, non-toxic and environmentally benign catalyst-
Iodine at 25 ꢀC is a remarkable feature of the procedure.
ACKNOWLEDGMENT
One of the authors, M. B. M. R., wishes to thank Mr. Manjunath, K. Math-
ematics teacher, St. Claret School, Jalahalli Village, Bengaluru-560013, Karnataka,
India, for constant encouragement.

3732
M. B. M. REDDY, A. NIZAM, AND M. A. PASHA
REFERENCES
1. (a) Deli, J.; Lorand, T.; Szabo, D.; Foldesi, A. Potential bio-active pyrimidine Derivatives
1: 2-Amino-4-aryl-8-arylidene-3,4,5,6,7,8-hexahydrochinazolines. Pharmazie 1984, 39,
539–540; (b) Guilford, W. J.; Shaw, K. J.; Dallas, J. L.; Koovakkat, S.; Lee, W.; Liang,
A.; Light, D. R.; McCarrick, M. A.; Whitlow, M.; Ye, B.; Morrissey, M. M. Synthesis, cha-
racterization, and structure–activity relationships of amidine-substituted (bis)benzylidene-
cycloketone olefin isomers Novel Bisarylmethylidenes of Cyclic Enones as potent and
selective factor Xa inhibitors. J. Med. Chem. 1999, 42, 5415–5425; (c) Artico, M.; Di Santo,
R.; Costi, R.; Novellino, E.; Greco, G.; Massa, S.; Tramintano, E.; Marongiu, M. E.;
De Montis, A.; La Colla, P. Geometrically and conformationally restrained cinnamoyl
compounds as inhibitors of HIV-1 integrase: Synthesis, biological evaluation, and
molecular modeling. J. Med. Chem. 1998, 41, 3948–3960; (d) Jia, Z. C.; Quail, J. W.;
Arora, V. K.; Dimmock, J. R. Structure of 3,5-bis(benzylidene)-1-methyl-4-piperidone
methobromide hemithanol solvate. Acta Cryst., Sect. C. 1989, 45, 1117–1118; (e)
Gangadhara, K. K. Synthesis and characterization of photo-cross-linkable main-chain
liquid-crystalline polymers containing bis(benzylidene)cycloalkanone units. Polymer 1995,
36, 1903–1910.
2. (a) Ward, D. E.; Nixey, T. E.; Gai, Y.; Hrapchak, M. J.; Abaee, M. S. Intramolecular
Diels–Alder reactions of 2H-thiopyran dienes. Can. J. Chem. 1996, 74, 1418–1436; (b)
Ward, D. E.; Abaee, M. S. Intramolecular DielsÀAlder Reaction by Self-Assembly of
the Components on a Lewis Acid Template. Org. Lett. 2000, 2, 3937–3940; (c) Ward, D.
E.; Sales, M.; Chuk, C. M.; Jianheng, S.; Pradip, K. S.; Cheng, G. Influence of the
b-Alkoxy Group on the Diastereoselectivity of Aldol Reactions of Tetrahydro-4H-
thiopyran-4-one with 4-Alkoxytetrahydro-2H-thiopyran-3-carboxaldehydes. J. Org. Chem.
2001, 67, 1618–1629.
3. Mai, A.; Cheng, D.; Bedford, M. T.; Valente, S.; Nebbioso, A.; Perrone, A.; Brosch, G.;
Sbardella, G.; De Bellis, F.; Miceli, M.; Altucci, L. Epigenetic multiple ligands: Mixed
histone=protein methyltransferase, acetyltransferase, and class III deacetylase (sirtuin) inhi-
bitors. J. Med. Chem. 2008, 51(7), 2279–2290.
4. Abaee, M. S.; Mojtahedi, M. M.; Zahedi, M. M.; Sharifi, R. A highly efficient method for
solvent-free synthesis of bisarylmethylidenes of pyranones and thiopyranones. Heteroatom
Chem. 2007, 18(1), 44–49.
5. Abaee, M. S.; Mojtahedi, M. M.; Zahedi, M. M.; Bolourtchian, S. M. First highly efficient
synthesis of bis(arylmethylidene)pyranones mediated by lithium perchlorate. Synth.
Commun. 2006, 36(2), 199–206.
6. Costi, R.; Santo, R. D.; Artico, M.; Massa, S.; Ragno, R.; Loddo, R.; La Colla, M.;
Tramontano, E.; La Colla, P.; Pani, A. 2,6-Bis(3,4,5-trihydroxybenzylydene) derivatives
of cyclohexanone-novel potent HIV-1 integrase inhibitors that prevent HIV-1 multipli-
cation in cell-based assays. Bioorg. Med. Chem. Lett. 2004, 12(1), 199–215.
7. Abaee, M. S.; Mojtahedi, M. M.; Zahedi, M. M.; Mesbah, A. W.; Ghandchi, N. M.;
Massa, W. Phosphorus, Sulfur, Silicon. 2007, 182, 2891–2895.
8. (a) Banik, B. K.; Fernandez, M.; Alvarez, C. Iodine-catalyzed highly efficient Michael reac-
tion of indoles under solvent-free condition. Tetrahedron Lett. 2005, 46, 2479–2482; (b)
Hessian, K. O.; Flynn, B. L. Iodine-induced reaction cascades for the rapid construction
of variously substituted benzothiophenes. Org. Lett. 2003, 5, 4377–4380.
9. (a) Madhusudana Reddy, M. B.; Pasha, M. A. Molecular iodine catalyzed mild, effective
and eco-friendly microwave assisted one-pot synthesis of 5-arylmethylidene-2-
phenyloxazol-4-ones (azalactones) under solvent-free condition. Synth. Commun. 2009
(LSYC-2009-2879, In press); (b) Pasha, M. A.; Jayashankara, V. P.; Swamy, N. R. A

SYNTHESIS OF 3,5-BIS-(ARYLMETHYLIDENE)-PYRAN-4-ONES
3733
simple and efficient procedure for the one pot synthesis of b-acetamido-b-
aryl-propiophenones by molecular iodine catalyzed Tandem reaction. Synth. Commun.
2007, 37, 1551–1556; (c) Pasha, M. A.; Jayashankara, V. P. Molecular iodine catalyzed syn-
thesis of aryl-14H-dibenzo[a,j]xanthenes under solvent free condition. Bioorg. Med. Chem.
Lett. 2007, 17, 621–623.