Microwave and BF3 promoted rearrangement of allyloxycoumarins to allylcoumarins and dihydrofurocoumarins

Article abstract of DOI:10.3987/com-01-9265

Allyl, crotyl, methallyl and cinamyl ethers of 4-hydroxy-, 7-hydroxy-, and 4-methyl-7-hydroxycoumarins have been efficiently synthesized and rearranged to substituted allylcoumarins under microwave irradiation. Irradiation of allylcoumarins in the presence of BF₃/ether directly produced substituted dihydrofurocoumarins in good yields.

Full text of DOI:10.3987/com-01-9265

HETEROCYCLES, Vol. 55, No. 9, pp. 1805 - 1812, Received, 5th June, 2001
MICROWAVE AND BF3 PROMOTED REARRANGEMENT OF
ALLYLOXYCOUMARINS TO ALLYLCOUMARINS AND
DIHYDROFUROCOUMARINS
Mohammad R. Saidi* and Fatemeh Rajabi
Department of Chemistry, Sharif University of Technology, PO Box 11365-9516,
Tehran, Iran
Abstract-Allyl, crotyl, methallyl and cinamyl ethers of 4-hydroxy-, 7-hydroxy-,
and 4-methyl-7-hydroxycoumarins have been efficiently synthesized and
rearranged to substituted allylcoumarins under microwave irradiation.
Irradiation of allylcoumarins in the presence of BF3/ether directly produced
substituted dihydrofurocoumarins in good yields.
Coumarins and furocoumarins are a class of natural compounds that in recent years have attracted
growing synthetic interest, while some of them have been found to be useful in photochemotherapy,
antitumoral, fragrances, agrochemicals and anti-HIV therapy or as CNS-active compounds.1 In the view
of the natural occurrence and useful range of biological activity associated with many
dihydrofurocoumarins, various methods have been developed for the synthesis of fused
dihydrofurocoumarins via Claisen rearrangement of allyl ethers and then acid-catalyzed cyclization of
allylcoumarins to dihydrofurocoumarins.2 In these reported methods, the Claisen rearrangement
reactions take place at boiling temperature in various solvents such as N,N-diethylaniline, N,N-
dimethylaniline, diphenyl ether, etc. for about 24 h. These procedures required vigorous reaction
conditions with tedious work-up procedure. Cyclization of allylcoumarins under acidic conditions,

usually sulfuric acid, resulted the expected dihydrofurocoumarins, but in low yields (Scheme 1). Cerric
ammonium nitrate, CAN, mediated formation of dihydrofurocoumarin from 4-hydroxycoumarin and α-
methylstyrene was recently reported by Kobayashi.3
N,N-DEA
reflux, 24 h
O
HO
O
O
O
O
H2SO4
O
HO
O
O
O
O
Scheme 1
Microwave-assisted organic synthesis has become an increasing used technique for the generation of
organic molecules and has attracted much attention due to enhanced reaction rates, increased yield,
selectivity and ease of manipulation of the product.4 One of the serious constraint in the use of
microwave ovens in organic synthesis is the selection of solvent for the reaction.5
In continuation of our work on microwave promoted selective rearrangement of propargyl naphthyl
ethers to naphthopyrans, naphthofurans, and application to the synthesis of natural lapachenole,
pyranocoumarins and furocoumarins,6 here we report a fast and cleaner method for rearrangement of
allyl, crotyl, methallyl and cinnamyl ethers of 4-hydroxycoumarin, 7-hydroxycoumarin, and 4-methyl-7-
hydroxycoumarin to substituted
allylcoumarins. The allyloxycoumarins were rearranged to
allylcoumarines under microwave irradiation in N-methylformamide, NMF (Scheme 2, Table1). The
irradiation time was between 18 to 22 min, and longer irradiation time did not increase the yield. By
addition of about 10 drops of water to the NMF (5 mL), the irradiation time decrease to 10 min with
almost the same yield. In the case of 7-allyloxycoumarin and 4-methyl-7-allyloxycoumarin small
amount of 6-allyl derivatives were also formed. The microwave promoted tandem Claisen
rearrangement-cyclization reaction of allyloxycoumarins in the presence of BF3 / ether directly produce

the dihydrofurocoumarins in good yields, Scheme 2. The results are summarized in Table 2. The
products obtained by microwave irradiation in NMF can be purified with more ease, since NMF is
soluble in water. The results clearly show that the rearrangement of allyloxycoumarins to allylcoumarins
and preparation of dihydrofurocoumarins via tandem Claisen rearrangement-cyclization reaction of
allyloxycoumarins in the presence of BF3 / ether using microwave irradiation are the best alternative for
preparation of these compounds.
R"
R"
HO
O
O
NMF, H2O
MW, 10 min
O
O
R
O
R
R'
R'
R"
O
R"
BF3 / ether, NMF
MW, 10 min
O
O
O
O
R
O
R'
R
R'
R = H, Me or Ph; R' = H or Me; R" = H or Me
Scheme 2
The allyl, crotyl, methallyl and cinnamyl ethers of 4-hydroxy-, 7-hydroxy-, and 4-methyl-7-
hydroxycoumarins were prepared from the corresponding coumarins and allyl, crotyl, methallyl and
cinnamyl chloride or bromide in refluxing dry acetone in the presence of potassium carbonate.7 All the
products have been characterized through IR, MS and NMR spectra and by comparison with those
reported in the literature.
EXPERIMENTAL
1
IR spectra were taken on Matt Son 1000 Unicam FTIR spectrophotometer. H and 13C NMR spectra
were recorded on Bruker AC 80 spectrometer in CDCl3. MS spectra were obtained on Fisson 800 Trio,
and GC-Mass HP 5973 MSD.

General Procedure for the Preparation of Allyloxycoumarins (1-3). - To a solution of hydroxycoumarin
(1.62 g, 10 mmol) in acetone (100 mL), K2CO3 (2.8 g, 20 mmol), and allyl bromide (1.8 g, 15 mmol)
were added. The resulting mixture was refluxed for 6 h (TLC monitoring). After cooling, the solvent
was evaporated, the residue poured into water (100 mL) and extracted with CH2Cl2 (3 x 20 mL), the
combined extract washed with brine, dried over MgSO4, and evaporated to get a white solid. The white
solid crystallized from ether if needed. Allyloxycoumarins (1-3) are known compounds, and their
spectroscopic data were similar to those reported in the literature.7
Table 1: Rearrangement of allyloxycoumarins to allylcocoumarins in
NMF under microwave irradiation
Substrate
R
Product
Yield (time)
% (min)
R
R
R = H
R = Me
1a
1b
75(22)
74(18)
O
O
R
O
O
HO
O
O
R
O
2a 65(20)
2b
R = H
R = Me
68(22)
O
O
O
HO
R
O
R
O
R = H
R = Me
70(18)
74(18)
3a
3b
O
O
HO
O
General Procedure for the Rearrangement of Allyloxycoumarins to Allylcoumarins in a Microwave
oven6.- Allyloxycoumarin (1.5 mmol) was dissolved in NMF (5 mL) and about 10 drops of water was
added. The mixture was placed in a sealed Teflon container (screw cap type, 50 mL), and subjected to
microwave irradiation with high power for 20 min. The mixture was diluted with water (20 mL), and the
product extracted with ether (3 x 20 mL). Further purification of the crude reaction mixture on silica gel

column, eluting with hexane-ethyl acetate (2:1) gave the pure product.
Table 2: Rearrangement of allyloxycoumarin to dihydrofurocoumarin in
the presence of NMF, BF/ether in microwave oven
3
Substrate
R
Product
Yield (time)
% (min)
R
R
R = H
R = Me
70(18)
74(18)
1a
1b
O
O
O
O
O
R
O
O
R
O
68(20)
65(20)
2a
2b
R = H
R = Me
O
O
O
O
R
R
O
74(18)
70(18)
3a
3b
R = H
R = Me
O
O
O
O
O
O
O
65(20)
4a
5a
6a
O
O
O
O
O
O
50(20)
45(22)
O
O
O
O
O
O
O
O
O
O
R
R
Ph
7a 52(25)
7b
O
R = H
R = Me
50(22)
O
O
O
O
O
Ph

General Procedure for the Rearrangement of Allyloxycoumarins to dihydrofuranocoumarins with
BF3/Ether under Microwave Irradiation.- Allyloxycoumarin (1.5 mmol) was dissolved in NMF (5 mL)
and 1.0 mL of BF3/ether was added. The mixture was placed in a sealed Teflon container (screw cap
type, 50 mL), and subjected to microwave irradiation with high power for 20 min. The mixture was
diluted with water (20 mL), and the product extracted with ether (3 x 20 mL). Further purification of the
crude reaction mixture on silica gel column, eluting with hexane-ethyl acetate (2:1) gave the pure
product.
0
0
0
Dihydrofurocoumarin (4a); mp 112-113 C, lit.,2 114 C. Dihydrofurocoumarin (4b); mp 129-130 C.
0
0
0
Dihydrofurocoumarin (5a); mp 108 C, lit.,2 105-106 C. Dihydrofurocoumarin (5b); mp 110-112 C.
Dihydrofuranocoumarin (6a); oil; 1H NMR (CDCl3): δ 1.20 (d, J = 6.5 Hz, 3H), 1.35 (d, J = 6.5 Hz, 3H),
3.00-3.75 (m, 1H), 4.28-5.98 (m, 1H), 6.09 (d, J= 9.5 Hz, 1H), 6.21-7.30 (m, 2H), 7.50 (d, J = 9.5 Hz,
1H). IR (KBr): ν, 1735, 1515, 1461, 1261 cm-1. MS: 216 (M+), 201 (base peak). Dihydrofurocoumarin
(6b); oil; 1H NMR (CDCl3): δ 1.28 (d, J = 6.5 Hz, 3H), 1.41 (d, J = 6.5 Hz, 3H), 2.33 (s, 3H), 3.04-3.70
(m, 1H), 4.25-5.94 (m, 1H), 6.04 (s, 1H), 6.50-7.50 (m, 2H). IR (KBr): ν, 1707, 1569, 1361, 1300 cm-1.
MS: 230 (M+), 215 (base peak). Dihydrofurocoumarin (7a); oil; 1H NMR (CDCl3): δ 1.50 (d, J = 6.4 Hz,
3H), 2.25-3.70 (m, 2H), 4.75-5.50 (m, 1H), 6.50-7.71 (m, 4H). IR (KBr): ν, 1723, 1646, 1500, 1415,
1276 cm-1. MS: 202 (M+), 187 (base peak). Dihydrofurocoumarin (9a); oil; 1H NMR (CDCl3): δ 1.51 (s,
6H), 2.98 (s, 2H), 7.00-7.70 (m, 4H). IR (KBr): ν, 1715, 1638, 1500, 1376, 1259, 1092 cm-1. MS: 216
(M+), 201 (base peak), Anal. Calcd for C13H12O3: C, 72.21; H, 5.59. Found: C, 72.01; H, 5.65.
Dihydrofurocoumarin (10a); 1H NMR (CDCl3): δ 1.62 (d, J = 6.9 Hz, 3H), 3.95 (d, J = 7.2 Hz, 1H), 4.91
(m, 1H), 6.22 (d, J = 9.4 Hz, 1H), 6.40-7.60(m, 7H), 7.59 (d, J = 9.4 Hz, 1H),. IR (KBr): ν, 1730, 1615,
1453, 1253, 1123 cm-1. Anal. Calcd for C18H14O3: C, 77.68; H, 5.07. Found: C, 77.63; H, 5.16.
Dihydrofurocoumarin (10b), mp 230-232 0C, lit.,2 230 0C.

ACKNOWLEDGMENT
We would like to acknowledge Iranian National Research Council for partial financial support of this
work. We also thank “Volkswagen-Stiftung, Federal Republic of Germany” for financial support
towards the purchase of chemicals
REFERNCES
1. Y. Fall, C. Teran, M. Teijeira, L. Santana, and E. Uriarte, Synthesis, 2000, 643; L. Crombie, R. C. F.
Lones, and C. J. Palmer, J. Chem. Soc., Perkin Trans. 1, 1987, 317; B. T. Nagadjui, J. F. Ayafor, B.
L. Sondergam, and J. D. Candally, Phytochemistry, 1989, 28, 585; R. D. H. Murray, J. Medez, and S.
A. Brown, The Natural Coumarins: Occurrence, Chemistry and Biochemistry, Wiley, New York,
1982; E. M. A. Yakout, N. M. Ibrahim, Kh. M. Ghoneim, and M. R. H. Mahran, J. Chem. Res. (S),
1999, 652.
2. Y. R. Lee, B. S. Kim, and H. C. Wang, Tetrahedron Lett., 1998, 54, 12215; K. C. Majumdar and T.
Bhattacharyya, J. Chem. Res. (S), 1997, 244; Yu. M. Revenko and A. A. Shamshurin, Kim.
Geterotsikl. Soedin, 1970, 135; S. S. Madhava-Rao and K. N. Trivedi, Indian J. Chem., 1992, 31B,
488; A. K. Mitra, S. K. Mukhopadhyay, A. Misra, and A. Patra, Indian J. Chem., 1982, 21B, 834; A.
G. Gonzalez, Z. D. Jorge, and L. F. Rodriguez, An. Quim., Ser. C., 1883, 79, 191.
3. K. Kobayashi, K. Sakashita, H. Akamatsu, K. Tanaka, M. Uchida, T. Uneda, T. Kitamura, O.
Morikawa, and H. Konishi, Heterocycles, 1999, 51, 2881.
4. S. Galema, Chem. Soc. Rev., 1997, 26, 233; F. Langa, P. De la Cruz, A. De la Hoz, A. Diaz-Ortiz,
and E. Diez-Barra, Contemporary Org. Synth., 1997, 373; R. A. Abramovitch, Org. Prep. Proc. Intl.,
1991, 23, 683; D. M. P. Mingos and D. R. Baghurst, Chem. Soc. Rev., 1991, 20. 1; S. Caddick,
Tetrahedron, 1995, 51, 10403; C. R. Strauss and R.W. Trainer, Aust. J. Chem., 1995, 48, 1665.
5. R. J. Giguere, T. L. Bray, S. M. Duncan, and G. Majetich, Tetrahedron Lett., 1986, 27, 4945; R. N.
Gedye, F. E. Smith, and K. C. Westaway, Can. J. Chem., 1988, 66, 17; M. S. F. Lie Ken Jie and C.

Yan-Kit, Lipids, 1988, 23, 367; (d) R. A. Abramovitch, D. A. Abramovitch, K. Lyanar, and K.
Tamareslvy, Tetrahedron Lett., 1991, 32, 5251.
6. F. Matloubi Moghaddam, A. Sharifi, and M. R. Saidi, J. Chem. Res. (S), 1996, 338; M. R. Saidi and
K. Bigdeli, J. Chem. Res. (S), 1998, 800.
7. Y.-L. Chen, T.-C. Wang, and C.-C. Tzeng, Helv. Chim. Acta, 1999, 82, 191; V. Stanjek and W.
Boland, Helv. Chim. Acta, 1998, 81, 1596; C. Teran, R. Miranda, L. Santana, M. Teijeira, and E.
Uriarte, Synthesis, 1997, 1384.