ZrOCl2·8H2O catalyzed solvent-free synthesis of isobenzofuran-1(3H)-ones

Article abstract of DOI:10.1016/j.cclet.2010.09.026

ZrOCl₂·8H₂O catalyzed environmentally benign synthesis of isobenzofuran-1(3H)-ones are described. ZrOCl₂· 8H₂O appeared to be an excellent catalyst for the condensation and reactions. Reaction of phthalaldehydic acid (2-carboxybenzaldehyde) with methylaryl and cyclic ketones was initiated by condensation and occurred in one step providing excellent yields (90-98%).

Full text of DOI:10.1016/j.cclet.2010.09.026

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 163–166
www.elsevier.com/locate/cclet
ZrOCl2Á8H2O catalyzed solvent-free synthesis of
isobenzofuran-1(3H)-ones
*
Jaiprakash N. Sangshetti, Siddique Akber M.K. Ansari, Devanand B. Shinde
Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004 (MS), India
Received 13 May 2010
Abstract
ZrOCl2Á8H2O catalyzed environmentally benign synthesis of isobenzofuran-1(3H)-ones are described. ZrOCl2Á8H2O appeared
to be an excellent catalyst for the condensation and reactions. Reaction of phthalaldehydic acid (2-carboxybenzaldehyde) with
methylaryl and cyclic ketones was initiated by condensation and occurred in one step providing excellent yields (90–98%).
# 2010 Published by Elsevier B.V. on behalf of Chinese Chemical Society.
Keywords: 2-Carboxybenzaldehyde; Methylaryl and cyclic ketones; ZrOCl2Á8H2O catalyst
The substituted phthalides (isobenzofuran-1(3H)-ones) represent an important class of natural products that posses
significant biological properties [1] In particular, 3-substituted phthalides are vital heterocyclic motifs in many
bioactive compounds such as iso-coumarins, anthraquinones, anthracyclines, and several alkaloids [2]. Their notable
characteristics include anti-bacterial, anti-convulsant, anti-HIV, anti-asthmatic, anti-tumor, anti-platelet activities,
anesthesia prolongation, and PGF2a inhibitory properties [3]. 3-Alkylidene phthalide derivatives are known for their
anti-spasmodic, herbicidal, and insecticidal properties and 3-styryl phthalides are used as color formers for heat and
pressure sensitive recording materials [4]. 3-Aryl phthalides are widely accepted synthons for the elaboration to
polycyclic compounds. 3-phenacylphthalides, i.e., 3-[2-oxo-2-phenylethyl 3H isobenzofuran 1-one], and its
derivatives are used as softening agents [5]. These phthalides are easily converted into (a) 3-phenacylidene phthalides,
known for their plant growth regulatory activity [6,7] (b) 3-alkylidene phthalides, known for their biological
importance [8] and (c) 3-styryl phthalides which are used as color formers for heat and pressure-sensitive recording
materials [9]. The literature survey revealed that 3-phenacylphthalides are synthesized by reacting 2-
bromobenzaldehyde with 1,3 dicarbonyl compounds under catalytic [10] conditions in the presence of alkali
[6,11]. The method to obtain 3-phenacylphthalides in one step was not reported yet. Recently we reported that the
reaction of phthalaldehydic acid with various aromatic methyl ethers in the presence of TFA provided 3-aryl
phthalides in good yields [12]. This observation led us to explore the reaction of phthaladehydic acid with
acetophenone which gave 3-phenacylphthalide in good yield. Substituted acetophenones and phthaladehydic acid
1
gave products which were fully characterized by H NMR (Scheme 1).
* Corresponding author.
E-mail address: dbshinde.2007@rediffmail.com (D.B. Shinde).
1001-8417/$ – see front matter # 2010 Published by Elsevier B.V. on behalf of Chinese Chemical Society.
doi:10.1016/j.cclet.2010.09.026

[()TD$FIG]
164
J.N. Sangshetti et al. / Chinese Chemical Letters 22 (2011) 163–166
O
O
O
ZrOCl2.8H2O
10mol %
OH
+
R1
O
Solvent free
120oC
O
O
1
2
3a-3i
Scheme 1. Synthesis of isobenzofuran-1(3H)-ones using ZrOCl2Á8H2O catalyst under solvent free condition.
R1
1. Experimental
Melting points are uncorrected and listed in Table 1 for all the products. 1H NMR spectra were recorded on a Varian
Gemini 200 MHz spectrometer. Chemical shifts are reported in d units relative to TMS as internal standard. Electron
spray ionization mass spectra (ES-MS) were recorded on a Water-Micromass Quattro-II spectrometer. All the reagents
used were of AR grade and were used without further purification.
Table 1
Synthesis of isobenzofuran-1(3H)-ones in solvent-free conditions.
Entry
Ketone
Product
Time/(h)
2.5
Yield/ (%)
98
Melting point
Found
Reported
145 [14]
O
O
145
3a
O
[TD$INLINE]
O
[DT$INLE]
O
O
2.5
92
96
209
146
3b
3c
O
210 [13]
[TD$INLINE]
O
[DT$INLE]
O
N
2
NO
2
O
O
2.25
146 [13]
O
[TD$INLINE]
O
Cl
[DT$INLE]
Cl
O
2.5
94
94
104
[TD$INLINE]
3d
3e
105[16]
78[16]
O
O
O
[DT$INLE]
O
O
O
EtO
2.25
[TD$INLINE]
79
O
O
O
[DT$INLE]
O
O
OEt
O
O
O
2.5
92
220
3f
219[13]
[TD$INLINE]
O
[DT$INLE]
H
CO
3
OMe

J.N. Sangshetti et al. / Chinese Chemical Letters 22 (2011) 163–166
165
Table 1 (Continued )
Entry
Ketone
Product
Time/(h)
2.25
Yield/ (%)
94
Melting point
Found
Reported
149[13]
O
O
149
3g
O
[TD$INLINE]
O
[DT$INLE]
CH
3
O
O
O
2.25
2.5
97
92
166
134
[TD$INLINE]
3h
3i
165–167[17]
O
[DT$INLE]
O
HO
O
O
135 [13]
H
[TD$INLINE]
C
3
O
O
[DT$INLE]
OH
OH
H3C
A mixture of phthalaldehydic acid (1 mmol), ketone (1.2 mmol) and ZrOCl2Á8H2O (0.1 mmol) was treated at
120 8C under solvent free condition for the appropriate time as indicated in Table 1. The progress of the reaction was
monitored by TLC [solvent system: (ethyl acetate):(hexane) = 1:4]. After completion of the reaction, residue was
extracted with CH2Cl2:H2O. The pure products were obtained by recrystallization using EtOH in 90–98% yields. All
1
the synthesized compounds were characterized by H NMR, mass spectrometry (ES-MS).
The representative analytical data for 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-one (3a): H NMR (CDCl3,
1
200 MHz): d 8.00–7.66 (m, 9H), 6.123–6.043 (t, 1H), 3.864–3.808 (d, 1H), 3.755–3.691 (d, 1H); ES/MS m/z (%):
253(M+H). C16H12O3 calcd. (%): C, 76.18, H, 4.79. Found (%): C, 76.22, H, 4.77.
2. Results and discussion
A mixture of phthalaldehydic acid (1 mmol), ketone (1.2 mmol) and ZrOCl2Á8H2O (0.1 mmol) was treated at
120 8C under solvent free condition for the appropriate time as indicated in Table 1. Having established the
reaction conditions, various isobenzofuran-1(3H)-ones were synthesized in excellent yields by the reaction
of different aromatic methyl ketones with phthalaldehydic acid and several representative examples are
summarized in Table 1. The progress of the reaction was monitored by TLC [solvent system: (ethyl
acetate):(hexane) = 1:4]. After completion of the reaction mixture was extracted with CH2Cl2:H2O. Different
diketo compounds containing active methylene group reacts with similar ease and forms the corresponding
products 3d, 3e, and 3h in shorter time than reported [10,15–17]. The pure products were obtained by
recrystallization using EtOH–H2O (1:3) in 90–98% yields. All the synthesized compounds were characterized by
1H NMR and mass spectrometry (ES-MS).
3. Conclusion
In conclusion novel and highly efficient methodology for the synthesis of isobenzofuran-1(3H)-ones by one pot
reaction condensation reaction of acetophenone, phthalaldehydic acid catalyzed by ZrOCl2Á8H2O has been
established. This method offers several significant advantages such as, high conversions, easy handling, clean reaction
profile and shorter reaction times, which makes it a useful and attractive process for the rapid synthesis of substituted
isobenzofuran-1(3H)-ones.

166
J.N. Sangshetti et al. / Chinese Chemical Letters 22 (2011) 163–166
Acknowledgments
The authors are thankful to the Head of the Department of Chemical Technology, Dr. Babasaheb Ambedkar
Marathwada University, Aurangabad 431004 (MS), India for providing the laboratory facility.
References
[1] (a) R. Pedrosa, S. Sayalero, M. Vicente, Tetrahedron 62 (2006) 10400;
(b) X.Z. Zhu, X.Y. Li, J. Liu, Eur. J. Pharmacol. 500 (2004) 221;
(c) G. Lin, S.S.K. Chan, H.S. Chung, S.L. Li, in: Atta-ur-Rahman (Ed.), Studies in Natural Products Chemistry, 32, Elsevier, Amsterdam,
2005, p. 611.
[2] (a) P. Pahari, B. Senapati, D. Mal, Tetrahedron Lett. 45 (2004) 5109;
(b) D. Mal, P. Pahari, S.R. De, Tetrahedron 63 (2007) 11781.
[3] (a) J. Safari, H. Naeimi, A.A. Khakpour, et al. J. Mol. Catal. A 270 (2007) 236;
(b) H. Yang, G.Y. Hu, J. Chen, et al. Bioorg. Med. Chem. Lett. 17 (2007) 5210;
(c) S. Mor, S.N. Dhavan, M. Kapoor, D. Kumar, Tetrahedron 63 (2007) 594.
[4] M.V. Paradkar, S.Y. Gadre, T.A. Pujari, et al. Synth. Commun. 35 (2005) 471.
[5] R.G. Haber, A. Ebnother, H. Schmidt, Helv. Chim. Acta 39 (1956) 1529.
[6] E.W. Bousquet, M.D. Moran, J. Harmon, et al. J. Org. Chem. 40 (1975) 2208.
[7] J.A. Houbin, M.W. Dayawan, Monsanta Co. (1981).
[8] R.S. Mali, S.R. Patil, B.K. Kulkarni, et al. Indian J. Chem. 29B (1990) 319.
[9] R.S. Mali, A.P. Massey, Synth. Commun. 27 (1997) 1049.
[10] D.Y. Lee, C.S. Cho, L.H. Jiang, et al. Synth. Commun. 27 (1997) 3449.
[11] J.N. Chatterjea, S.C. Bhakta, A.K. Chattopadhyay, J. Indian Chem. Soc. 17 (1974) 757.
[12] M.V. Paradkar, A.A. Ranade, A.R. Joseph, et al. J. Chem. Res. (1998) 332.
[13] V.P. Madhusudan, Y.G. Suhas, A.P. Twarita, et al. Synth. Commun. 35 (2005) 471.
[14] J.R. Geigy, Chem. Abstr. 66 (1967) 10791.
[15] C. Donati, R.H. Prager, B. Weber, Aust. J. Chem. 42 (1989) 787.
[16] M. Dipakranjan, P. Pallab, Saroj, Tetrahedron 63 (2007) 11781.
[17] S.M. Landge, M. Berryman, B. Torok, Tetrahedron Lett. 49 (2008) 4505.