Zirconium(IV) chloride catalyzed cyclization of ortho-allylphenols: Synthesis of 2-methyl-2,3-dihydrobenzofurans

Article abstract of DOI:10.1081/SCC-200028551

Intramolecular cyclization of ortho-allylphenols has been carried out using zirconium (IV) chloride in mild condition. This method avoids the use of expensive reagents and leads to highly functionalized dihydrobenzofurans.

Full text of DOI:10.1081/SCC-200028551

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Zirconium(IV) Chloride
Catalyzed Cyclization
of ortho‐Allylphenols:
Synthesis of
2
‐Methyl‐2,3‐dihydrobenzofurans
a a
H. M. Meshram , K. Premalatha , K.
a
a
a
Rameshbabu , B. Eeshwaraiah & J. S. Yadav
a
Organic Division I , Indian Institute of Chemical
Technology , Hyderabad, 500 007, India
Published online: 10 Jan 2011.
To cite this article: H. M. Meshram , K. Premalatha , K. Rameshbabu , B.
Eeshwaraiah & J. S. Yadav (2004) Zirconium(IV) Chloride Catalyzed Cyclization
of ortho‐Allylphenols: Synthesis of 2‐Methyl‐2,3‐dihydrobenzofurans, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 34:17, 3091-3097, DOI: 10.1081/SCC-200028551
To link to this article: http://dx.doi.org/10.1081/SCC-200028551
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SYNTHETIC COMMUNICATIONS
Vol. 34, No. 17, pp. 3091–3097, 2004
Zirconium(IV) Chloride Catalyzed
Cyclization of ortho-Allylphenols: Synthesis
of 2-Methyl-2,3-dihydrobenzofurans
*
H. M. Meshram, K. Premalatha, K. Rameshbabu,
B. Eeshwaraiah, and J. S. Yadav
Organic Division I, Indian Institute of Chemical Technology,
Hyderabad, India
ABSTRACT
Intramolecular cyclization of ortho-allylphenols has been carried out
using zirconium (IV) chloride in mild condition. This method avoids
the use of expensive reagents and leads to highly functionalized
dihydrobenzofurans.
Key Words: ortho-Allylphenols; Intramolecular cyclization; Zirconium
(
IV) chloride; Dihydrobenzofurans.
*
Correspondence: H. M. Meshram, Organic Division I, Indian Institute of Chemical
Technology, Hyderabad 500 007, India; Fax: þ091 40 7170512; E-mail: hmmeshram@
yahoo.com.
3
091
DOI: 10.1081/SCC-200028551
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

3
092
Meshram et al.
2
products
,3-Dihydrobenzofuran nuclei are found in a variety of bioactive natural
[
1a–c]
[2]
and therapeutic agents. Particularly, carboxylic acid deriva-
tives I and II show antiinflammatory and antioxidant activity.
Generally, 2,3-dihydrobenzofuran systems are constructed by the
to accom-
[3–6]
cyclization of ortho-allylphenols. There are various methods
plish this cyclization in different reacton conditions. However, most of the
methods have the drawbacks of using harsh reaction conditions and expensive
metal salts. So there is still need to develop a mild and simple procedure
for the cyclization of ortho-allylphenols. Recently, zirconium (IV) chloride
has attracted more attention because of its diverse application in organic
[7–13]
[14]
synthesis.
Our involvement in metal catalyzed reactions
prompted
us to perform zirconium (IV) chloride catalyzed cyclization of ortho-
allylphenols, which leads to 2-methyl-2,3-dihydrobenzofuran containing
ample functionality.
Thus zirconium (IV) chloride was added to ortho-allylphenol in dichloro-
methane at 08C and stirred at room temperature (see Table 1) under nitrogen
atmosphere. After work-up, 2-methyl-2,3-dihydrobenzofurans were isolated
in good yield. The reaction proceeded with a stoichiometric (1 : 1) amount
of zirconium (IV) chloride, but it could be accelerated by the addition of
1
: 1.2 equivalents of zirconium (IV) chloride. In case of allylphenol bearing
alkyl keto subsistent (entry 1 and 2), the reaction proceedes with one equi-
valent of zirconium (IV) chloride with high yields. In case of aryl keto substi-
tuents (entry 3), the reactions were sluggiish. The reaction was also sluggish
and incomplete with the substrate having free acid (entry 4 and 5). The rate
Scheme 1.

Zirconium(IV) Chloride Catalyzed Cyclization of ortho-Allylphenols
3093
Table 1. Zirconium (IV) chloride catalyzed cyclization of ortho-allylphenols.
a
Entry
1
Substrate
Time (hours)
12
Product
Yield (%)
70
2
3
10
15
71
b
60
b
4
5
20
20
60
b
60
6
7
12
10
85
85
8
9
12
10
70
80
10
8
80
a
Isolated yield.
Remaining starting material recovered.
b

3
094
Meshram et al.
of reaction could be enhanced by using methyl ester (entry 6 and 7) and amide
entry 9 and 10) functionalities; however, aryl ester (entry 8) was found to
(
suppress the reaction. We had examined the reaction in different solvents
like dichloromethane, tetrahydrofuran, and acetonitrile, but dichloromethane
gave better yields.
In conclusion, we have demonstrated a simple and mild method for the
cyclization of ortho-allylphenols. This procedure is applicable for the syn-
thesis of functionalized 2-methyl-2,3-dihydrobenzofurans, which may find
applications in drug discovery.
EXPERIMENTAL PROCEDURE
Boiling points and melting points are uncorrected. Melting points were
recorded on Buchi R535 apparatus. The infrared (IR) spectra were recorded
1
on Nicole 740 FT IR spectrometer; H nuclear magnetic resonance (NMR)
spectra were recorded on FT (200 and 300 MHz Gemini) spectrometer.
Mass spectra were recorded on either Micromass 7070 h or Finnigan Mat
1020 B mass spectrometer operating at 70 eV. Thin layer chromatography
was done on precoated silica gel 60f 254 (0.5 mm) glass plates.
Typical Experimental Procedure
The solution of ortho-allylphenol (10 mmol) in dichloromethane (40 mL)
was cooled to 08C and zirconium (IV) chloride (10 mmol) was added in por-
tions. The stirring was continued for stipulated period of time (see Table 1).
After completion, it was quenched with water and the organic layer separated.
The aqueous layer was extracted with more dichloromethane. The combined
organic phase was washed with water, dried over sodium sulfate, and concen-
trated to give the crude product, which was purified by silica gel column
chromatography and characterized by mass and NMR spectral data.
SPECTRAL DATA FOR SELECTED COMPOUNDS
1
2
a: Liquid; H NMR (300MHz, CDCl ) d: 1.45 (d, J ¼ 8.43Hz, 3H), 2.52
3
(
s, 3H), 2.82 (dd, J ¼ 6.5 Hz, 12.8Hz, 1H), 3.38 (dd, J ¼ 6.5 Hz, 12.8Hz, 1H),
4
.9–5.05 (m, 1H), 6.7 (d, J ¼ 14.06 Hz, 1H), 7.75 (d, J ¼ 14.24 Hz, 2H). MS
m/z) (relative intensity) 176 (34), 161 (100), 43 (20). Anal. Calcd. for
C H O : C, 74.98; H, 6.86; Found: C, 74.94; H, 6.80.%
(
1
1 11 2

Zirconium(IV) Chloride Catalyzed Cyclization of ortho-Allylphenols
3095
1
2
b: Liquid; H NMR (200 MHz, CDCl ) d: 1.19 (t, J ¼ 8.16 Hz, 3H), 1.55
3
(
d, J ¼ 6.9 Hz, 3H), 2.88 (dd, J ¼ 6.8 Hz, 13.0 Hz, 1H), 2.98 (q J ¼ 7.9 Hz,
H), 3.32 (dd, J ¼ 6.8 Hz, 13.0 Hz, 1H), 4.98–5.08 (m, 1H), 6.82
2
(
t, J ¼ 7.4 Hz, 1H), 7.22 (d, J ¼ 7.82 Hz, 1H), 7.62 (d, J ¼ 9.56 Hz, 1H).
MS (m/z) (relative intensity) 190 (20), 161 (100), 105 (18). Anal. Calcd.
for C H O : C, 75.76; H, 7.42; Found: C, 75.79; H, 7.39.%
1
2 13 2
1
2
c: Liquid; H NMR (200 MHz, CDCl ) d: 1.42 (d, J ¼ 8.3 Hz, 3H), 2.76
3
(
(
dd, J ¼ 6.9 Hz, 12.9 Hz, 1H), 3.29 (dd, J ¼ 6.9 Hz, 12.9 Hz, 1H), 4.94–4.99
m, 1H), 6.62 (d, J ¼ 10 Hz, 1H), 7.32–7.62 (m, 6H). MS (m/z) (relative
intensity) 239 (50), 162 (100), 105 (40). Anal. Calcd. for C H O : C,
1
6 13 2
8
0.65; H, 5.92; Found: C, 80.69; H, 5.90%.
1
2
d: Liquid; H NMR (300 MHz, CDCl ) d: 1.56 (d, J ¼ 7.14 Hz, 3H),
3
2
.85 (dd, J ¼ 6.5 Hz, 12.7 Hz, 1H), 3.35 (dd, J ¼ 6.5 Hz, 12.7 Hz, 1H),
.95–5.85 (m, 1H), 6.8 (t, J ¼ 7.6 Hz, 1H),7.25 (d, J ¼ 14.28 Hz, 1H), 7.68
4
(
d, J ¼ 13.98 Hz, 1H). Anal. Calcd. for C H O : C, 67.41; H, 5.66; Found:
1
0 9 3
C, 67.44; H, 5.68%.
2
1
e: Liquid; H NMR (200 MHz, CDCl ) d: 1.44 (d, J ¼ 6.9 Hz, 3H), 2.81
3
(
(
dd, J ¼ 7.0 Hz, 13.1 Hz, 1H), 3.32 (dd, J ¼ 7.0 Hz, 13.1 Hz, 1H), 4.90–5.05
m, 1H), 6.68 (d, J ¼ 7.69 Hz, 1H), 7.8 (d, J ¼ 6.1 Hz, 2H). Anal. Calcd. for
C H O : C, 67.41; H, 5.66; Found: C, 67.46; H, 5.61%.
1
0 9 3
1
2
g: Liquid; H NMR (200 MHz, CDCl ) d: 1.55 (d, J ¼ 6.6 Hz, 3H), 2.81
3
(
dd, J ¼ 6.8 Hz, 13.0 Hz, 1H), 3.32 (dd, J ¼ 6.8 Hz, 13.0 Hz, 1H), 3.84 (s, 3H),
4
.98–5.09 (m, 1H), 6.8 (t, J ¼ 7.5 Hz, 1H), 7.22 (d, J ¼ 7.5 Hz, 1H), 7.63
(
d, J ¼ 7.5 Hz, 1H). MS (m/z) (relative intensity) 192 (100), 161 (70), 105
(
33). Anal. Calcd. for C H O : C, 68.74; H, 6.29; Found: C, 68.78; H,
1
1 11 3
6
.32%.
2
1
i: Solid mp: 898C H NMR (200 MHz, CDCl ) d: 1.58 (d, J ¼ 6.08 Hz,
3
3
H), 2.86 (dd, J ¼ 6.9 Hz, 12.9 Hz, 1H), 3.4 (dd, J ¼ 6.92 Hz, 12.9 Hz, 1H),
.05–5.2 (m, 1H), 6.9 (t, J ¼ 7.82 Hz, 1H), 7.2–7.42 (m, 6H), 7.92
5
(d, J ¼ 8.82 Hz, 1H). Anal. Calcd. for C H O N: C, 73.38; H, 6.41; N,
1
7 16 2
5
.24: Found: C, 73.40; H, 6.46; N, 5.21%.
2
1
j: Liquid; H NMR (200 MHz, CDCl ) d: 1.45 (s, 2H), d 1.47
3
(
d, J ¼ 5.06, 3H), 2.91 (dd, J ¼ 6.1 Hz, 12.3 Hz, 1H), 3.35 (dd, J ¼ 6.1 Hz,
1
2.3 Hz, 1H), 4.95–5.1 (m, 1H), 6.92 (t, J ¼ 8.82 Hz, 1H), 7.15–7.35
(
m, 5H), 7.92 (d, J ¼ 8.84 Hz, 1H). Anal. Calcd. for C H O N: C, 73.38;
1
7 16 2
H, 6.41; N, 5.24; Found: C, 73.41; H, 6.42; N, 5.23%.
ACKNOWLEDGMENT
K. Premalatha is thankful to CSIR, New Delhi, for financial support in the
form of fellowship.

3
096
Meshram et al.
REFERENCES
1
. (a) Sih, C.J.; Ravikumar, P.R.; Huang, F.; Buckner, C.; Whitloc, H. Iso-
lation and synthesis of pinoresinol diglucoside, a major antihypertensive
principle of Tu Chung (Eucommio uhnoides, oliver). J. Am. Chem. Soc.
1
976, 98, 5412; (b) Nagai, M.; Noguchi, M.; Iizuka, T.; Otani, K.;
Kamata, K. Vascodilator effects of des(a-carboxy-3,4,dihydroxy phe-
nethy) lithospermic acid (8-epiblechnic acid), a derivative of lithospermic
acid in solviac Miltiorrhizae Radix. Biol. Pharm. Bull. 1996, 19,
2
28–232; (c) Nikaido, T.; Ohmoto, T.; Kinoshita, T.; Sankawa, H.;
Nishibe, S.; Hisada, S. Chem. Pharm. Bull. 1981, 29, 3586–3592.
. (a) Brufani, M.; Ceccarelli, S.; Giannetti, P.; Paesono, A.; Scuri, R.;
Zanarella, S Br. Pat. 2221 463 1990; (b) Preparation of (RS)-2-(2,3-
dihydro-5-hydroxy-4,6,7-trimethylbenzofuranyl) acetic acid, 2-(2,3-
dihydro-5-acyloxy-4,6,7-trimethylbenzofuranyl) acetic acid and their
esters. Antihypertensive drugs. Chem. Abstr. 1990, 113, 58915;
2
(
c) Brunmer, H. Euro. Pat. Offen. 2227423, s1972; (d) Chem. Abstr.
973, 78, 62181.
1
3
. (a) Maier, L. Organic phosphorus compounds 68. The direct synthesis of
tri (alkyl and aryl seleno) phosphites and of tris(p-anisyltelluro)
phosphite (1). Helv. Chim. Acta. 1976, 252; (b) KaraKhanov, E.A.;
Freger, A.A.; Viktorova, E.A. Mechanism of phenol synthesis during
reactions of 2,3-dihydrobenzofurans on acid catalysts. Izv. Vyssh Vche
Zagved Khim. Khim Tekhnol. 1973, 16 (4), 586–588.
4
. (a) Cho, J.Y.; Kyong, U.; Baik, K.U.; Yoo, E.S.; Yoshikawa, K.;
Park, M.H. In vitro anti-inflammatory effects of neolignonan wooreno-
sides from the rhizomes of Coptis japanica. J. Natl. Prod. 2000, 63,
1
205–1209; (b) Laszlo, J.; Laszlo, K.; Sandor, A. Simple synthesis of
benzofuranoid neolignane from Myristica fragrans. J. Natl. Prod. 2000,
3, 866–870.
6
5
6
7
8
. Bergman, J.; Engman, L. Oxidatuve cyclization of some g- and d-hydroxy
olefins indused by telurium dioxide. J. Am. Chem. Soc. 1981, 103,
5
196–5200.
. Hu, Y.; Zhang, Y.; Yang, Z.; Fathi, R. Palladium-catalyzed carbonylative
annulation of -o-alkynyl phenols: synthesis of 2- substitutes- 3-aroyl-
benzo(b) furans. J. Org. Chem. 2002, 67, 2365–2368.
. Evans, D.A.; Chapman, K.T.; Bisaha, J. Asymmetric Diels–Alder cyclo
addition reactions with chiral a,b-unsaturated N-acyloxazolidinones.
Am. Chem. Soc. 1988, 110, 1238.
. Yam, V.W.W.; Chong, S.H.F.; Chung, C.K.K. Synthesis and lumines-
cence behaviour of rhenium(I) diynl complexes. X-ray crystal structures

Zirconium(IV) Chloride Catalyzed Cyclization of ortho-Allylphenols
3097
of [Re(co)3(tBu2bpy)(C ;; C 22 C ;; C 22 H)] and [Re(Co)3(tBu2bpy)
C ;; C 22 C ;; C 22 ph)]. Chem. Commun. 1998, 19, 2121.
(
9
. Phillipson, N.; Anson, M.S.; Montana, J.G.; Taylor, R.J.K. Ketone homo-
logation to produce a-methoxy ketones: application to conduritol
synthesis. J. Chem. Soc. Perkin. Trans. I 1997, 19, 2821.
1
0. Lenarsic, R.; Kocevar, M.; Polane, S. ZrCl -Mediated regioselective
4
electrophilic amination of activated arenes with new alkyl aryl amino
carbonyl diazene carboxylates: intermolecular and intramolecular
reactions. J. Org. Chem. 1999, 64, 2558.
1
1. Caminade, A.-M.; Majorl, J.P; Joopknol; Ben, L.F. Phosphorhydrazide
macrocycles and cryptands. Synlett. 1996, 11, 1025.
1
2. Harrowven, D.C.; Dainty, R.F. Zirconium tetrachloride as a mediator for
ambient temperature ortho-Fries rearrangements. Tetrahedron Lett. 1996,
3
7, 7659.
3. Yadav, J.S.; Reddy, B.V.S.; Raj, K.S.; Reddy, K.B.; Prasad, A.R. Ze
Catalyzed efficient synthesis of a-amino phosphonates. Synthesis 2001,
5, 2277.
4
þ
-
1
1
1
4. (a) Yadav, J.S.; Reddy, G.S.; Meshram, H.M. Zinc promoted simple and
convenient synthesis of carbomates: an easy access for amino group
protection. Tetrahedron Lett. 1998, 39, 3259; (b) Meshram, H.M.;
Reddy, G.S.; Reddy, M.M.; Yadav, J.S. Zinc mediated facile amide
formation: application to alkyl, aryl, heterocyle, carbohydrate and
amino acids. Tetrahedron Lett. 1998, 39, 4103.
Received May 13, 2004