Novel and convenient synthesis of benzofurans from dihydrocoumarins

Article abstract of DOI:10.1002/jhet.896

7-Hydroxy-3,4-dihydrocoumarin-4-carboxylic acid (7), conveniently prepared from m-resorcinol and maleic anhydride, was surprisingly transformed by acid anhydride and pyridine into the corresponding ketone, 4-alkanoyl analog 11. The latter reacted in turn

Full text of DOI:10.1002/jhet.896

July 2012
Novel and Convenient Synthesis of Benzofurans from
Dihydrocoumarins
905
Sharona Shachan-Tov and Aryeh A. Frimer*
Ethel and David Resnick Chair in Active Oxygen Chemistry, Department of Chemistry,
Bar-Ilan University, Ramat Gan 52900, Israel
*
E-mail: frimea@mail.biu.ac.il
Received January 18, 2011
DOI 10.1002/jhet.896
View this article online at wileyonlinelibrary.com.
7
-Hydroxy-3,4-dihydrocoumarin-4-carboxylic acid (7), conveniently prepared from m-resorcinol and
maleic anhydride, was surprisingly transformed by acid anhydride and pyridine into the corresponding
ketone, 4-alkanoyl analog 11. The latter reacted in turn with acidic alcohol yielding benzofuran-3-yl-acetic
ester 16.
J. Heterocyclic Chem., 49, 905 (2012).
INTRODUCTION
9a in the presence of pyridine; the reaction was quenched
with methanol to solvolyze all the remaining anhydrides.
Much to our astonishment, the observed product was not
dihydrocoumarin diester 10a—with a C-NMR carbonyl
absorption at ca.172, but rather ketone 11a—with a car-
bonyl resonance at 207 ppm. This reaction repeated itself
as well with other anhydrides, 9b–e, yielding ketones
The benzofuran ring is a common moiety in many bio-
logically active natural and therapeutic products [1] and
represents a very important heterocyclic pharmacophore.
As a result, benzofuran-containing entities constitute an
important target for pharmaceutical research [2]. We de-
scribe our serendipitous discovery of a novel and conve-
nient synthetic route to this moiety, beginning with the
easily accessible 7-hydroxy-3,4-dihydrocoumarin system.
The coumarin system itself exhibits useful and diverse bio-
logical activity [3], and finds application in pharmaceuti-
cals, fragrances, agrochemicals, and insecticides [4].
Because of our studies on the superoxide mediate saponifi-
cation of coumarins [Scheme 1; eq. (1)] [5] we were inter-
ested in exploring a similar reaction with 3,4-dihydro
analogs 3 [eq. (2)].
13
1
1b–e in similar yields of about 30% (Scheme 3).
In our search for precedents, we discovered that more
than half-a-century ago, Lawson [4] described similar
examples of decarboxylative acylation with anhydrides.
A plausible mechanism for this transformation is outlined
in Scheme 4 [8]. The initial step is the expected acylation
of the hydroxyl groups of the C-7 phenol and the C-4
carboxylic acid, presumably yielding anhydride ester 12.
In the key step, facile deprotonation and subsequent acyla-
tion occurs at doubly activated C-4, which is both benzylic
and a to the anhydride carbonyl. The resulting b-ketoanhy-
dride 14 undergoes decarboxylation yielding the observed
ketone 11.
RESULTS AND DISCUSSION
To this end, we began with the Gunnewegh synthesis of
dihydrocoumarin 7 from resorcinol (5) and maleic anhydride
Another surprise awaited us when we attempted to
solvolyze the C-7 esters 11a–f. Instead of isolating dihy-
drocoumarins 15, we obtained benzofuran-3-yl acetates
16a–f in a 50% yield (Scheme 5) [7,9].
The proposed mechanism for this transformation
appears in Scheme 6. Alcoholysis of both the ester linkage
at C-7 and the lactone at C-2, generates m-cresol
17. Cyclization of the generated phenol into the ketone
carbonyl results in the formation of furanol 18, which
dehydrates in turn, generating benzofuran-3-yl-acetic
esters 16.
(
6), as shown in Scheme 2 [6]. The desired product
is obtained in a 60% yield along with variable amounts
0–30%) of a side product, ketone 8. The latter is formed in
a subsequent Friedel–Crafts addition of the primary product
on the starting resorcinol 5. The yield of this side product
can be decreased dramatically by lowering the concentra-
tions of the starting reagents (see the Experimental section).
In the next step (Scheme 3), we attempted to acylate the
phenolic group of coumarin 7 at C-7 with acetic anhydride
(
7
©
2012 HeteroCorporation

9
06
S. Shachan-Tov and A. A. Frimer
Vol 49
Scheme 1. Superoxide mediated saponification of coumarins 1 and
dihydrocoumarins 3.
Scheme 3. Acylation of dihydrocoumarin-4-carboxylic acid 7 with
anhydrides 9.
CONCLUSIONS
In conclusion, we have described a convenient synthesis
of a broad family of 6-hydroxybenzofurans 16 beginning
with 7-hydroxy-3.4-dihydrocoumarins 7 and proceeding
via coumarins 11. The double activation of C-4 in 11 and
the 1,4-relationship of the two carbonyls in dihydrocou-
marins 11 is at the core of the two surprising transforma-
tions observed.
ꢁ
Yield: 5 g (60%); mp 153–155 C. IR (KBr pellet) 1761 (CO
ꢂ1
1
ester), 1695 (CO) cm
. H-NMR (300 MHz, CD COCD ):
d 2.97 (1H, dd, J = 6.14 Hz and 17.7 Hz, H b), 3.1 (1H, dd,
3 3
3
13
J = 4 Hz and 17.7 Hz, H
75 MHz, CDCl ) d 35.06 (C-3), 40.05 (C-4), 99.11 (C-8),
11.36 (C-6), 118.57 (C-4 ), 125.43 (C-5), 155.88 (C-8 ),
3 4
a), 3.9 (1H, m, H ). C-NMR
(
1
3
0
0
EXPERIMENTAL
159.04 (C-7), 171.82 (C-2), 177.54 (C-9). HRMS, m/z (CI,
+
CH ): Calcd for C H O (M -H) 207.0293. Found 207.0289.
4
10 7 5
High-resolution mass spectra were run on a VG-Fison Auto-
SpecE high resolution spectrometer. The NMR spectra were
recorded on a Bruker AM 300 or Bruker DMX 600 Fourier trans-
form spectrometer. For 1D NMR spectra, we used a QNP probe.
All 2D experiments (COSY, HMQC, HMBC, and NOSEY) were
run using the programs from the Bruker software library. NMR
General procedure for the preparation of ketones 11a-e.
To a solution containing 7-hydroxy-3,4-dihydrocoumarin-4-
carboxylic acid (7; 0.009 mol), the desired anhydride 9 (acetic,
propionic, butyric, valeric or capric; 2 equiv, 0.019 mol), and
ꢁ
spectra were generally taken at 25 ꢀ 1 C and recorded while
Scheme 4. Mechanism for the transformation of dihydrocoumarin 7 to
ketones 11.
locked on the deuterium signals of the respective deuterated sol-
vent. The numbering of the carbons and hydrogens in the NMR
spectra of dihydrocoumarin 7, ketones 11, and benzofurans 16
are exemplified below in Scheme 7.
7-Hydroxy-3,4-dihydrocoumarin-4-carboxylic acid (7) [6].
A solution of resorcinol (5, 0.05 mol), maleic anhydride (6, 0.05
mol), and wet [10] amberlyst 15 ion exchange resin (5 g) in toluene
(500 mL) were refluxed while stirring with a mechanical stirrer
for 48 h. For isolation and purification of the compound, the resin
catalysts were removed by warm filtration, followed by carefully
and repeatedly washing the resin with acetone. The pure product
was isolated by acetone evaporation as a red solid.
Scheme 2. Gunnewegh synthesis of dihydrocoumarin 7.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2012
Novel and Convenient Synthesis of Benzofurans from Dihydrocoumarins
907
Scheme 5. Acid alcoholysis of dihydrocoumarin 11.
Scheme 6. Transformation of 4-acyldihydrocoumarin 11 to benzofuran
6.
1
pyridine (4 equiv, 0.038 mol, 3 mol), a catalytic amount of 4-
dimethylaminopyridine (56 mg) was added. The reaction
mixture was stirred at r.t. for 12 h. The reaction was quenched
with ice–cold methanol and evaporated. Water was then added
to the brown-red solution, and the aqueous reaction mixture was
extracted thrice with ethyl acetate. The combined ethyl acetate
extracts were washed with aqueous sodium bicarbonate solution
and evaporated, yielding crude 11. The latter was recrystallized
from a mixture of methanol and acetone to give a white solid.
The yield was consistently around 30%.
J
10
0
,11
0
= J11
0
,12
0
= 7.2 Hz, H11
0
), 0.97 (3H, t, J11
0
,12
0
= 7.2, H12 ),
0
13
0.75 (3H, t, J11,12 = 7.5, H12). C-NMR (75 MHz, acetone-d
d 208 (C-9 ), 172.04 (C-9), 166.68 (C-2), 153.39 (C-8 ), 152.27
(C-7), 130.45 (C-5), 118.92 (C-4 ), 118.63 (C-6), 111.84 (C-8),
48.16 (C-4), 42.38 (C-10 ), 36.31 (C-3), 18.87 (C-11), 17.37
(C-11 ), 13.72 (C-12 ), 13.72(C-12). HRMS, m/z (CI, CH ): Calcd
20 5
for C17H O (M ) 304.1311. Found 304.1274.
Pentanoic acid 4-pentanoyl-3,4-dihydrocoumarin-7-yl ester
(11d). Mp 111–114 C. IR (KBr pellet): 1765 (CO ester), 1695
(CO) cm . H-NMR (300 MHz ,CDCl
), 6.93 (1H, dd, J = 8.4 and 2.4 Hz, H
Hz, H ), 4.00 (1H, dd J = 5.7 and 2.1 Hz, H
J = 16.2 Hz and 2.4 Hz, H a), 2.71 (1H, dd, J = 16.2 Hz and 6.00
Hz, H b), 2.55 (4H, m, H10, ), 1.77 (2H, quint, J = 7.2, H11),
1.51 (4H, m, H11 and H12), 1.25 (2H, sex, J = 7.4, H12 ), 0.995
(3H, t, J12 = 7.2 Hz, H13 ), 0.84 (3H, t, J12,13 = 7.2 Hz, H13).
C-NMR d 206.48 (C-9 ), 171.78 (C-9), 165.88 (C-2), 152.44
(C-7), 151.51 (C-8 ), 128.87 (C-5), 118.06 (C-6), 117.32
(C-4 ),111.68 (C-8) , 47.84 (C-4), 39.96 (C-3), 34.05 (C-10 ),
30.67 (C-10), 26.91 (C-11), 25.47 (C-11 ), 22.22 (C-12), 22.11
6
)
0
0
0
0
0
0
4
+
ꢁ
ꢂ1
1
): d 7.33(1H, d ,J = 8.4,
), 6.84 (1H, dd, J = 2.4
), 3.10 (1H, dd,
3
Acetic acid 4-acetyl-3,4-dihydrocoumarin-7-yl ester (11a).
H
5
6
ꢁ
Mp 136–138 C, R
(
(
(
f
= 0.33 (30% ethyl acetate in hexane). IR 1769
8
4
ꢂ1
1
CO ester), 1698 (CO) cm . H-NMR (300 MHz, CDCl
1H, d, J = 8.4, H ), 6.95 (1H, dd, J = 8.4 and 2.4 Hz, H
1H, d, J = 2.0 Hz, H ), 3.90 (1H, dd, J = 6.5 and 2 Hz, H ), 3.10
3
): d 7.36
3
6
), 6.85
3
H
0
10
5
0
0
8
4
(
6
1H, dd, J = 15.3 and 2 Hz, H a), 2.69 (1H, dd, J = 15.3 and
0
,13
0
0
3
13
13
0
.5 Hz, H
3
b), 2.31 (3H, s, H10
0
), 2.26 (3H, s, H10). C-NMR
0
0
(75 MHz, CDCl
3
) d 204.21 (C-9 ), 169.13 (C-9), 166.09 (C-2),
0
0
0
1
52.42 (C-8 ), 151.45 (C-7), 129.22 (C-5), 118.31 (C-6), 117.22
0
0
+
0
(C-4 ), 111.83 (C-8), 48.49 (C-4), 30.51 (C-10), 27.71 (C-10 ),
0
0
2
1.24 (C-3). HRMS, m/z (CI, CH ): Calcd for C H O (MH )
(C-12 ), 13.67(C-13, C-13 ). HRMS, m/z (CI, CH ): Calcd for
C H O (MH ) 333.1711. Found 333.1702.
19 25 5
4
4
13 13 5
+
249.0790. Found 249.0763.
Propionic acid 4-propionyl-3,4-dihydrocoumarin-7-yl ester
Decanoic acid 4-decanoyl-3,4-dihydrocoumarin-7-yl ester
ꢁ
ꢂ1
(
(
11b). Mp 111–113 C. IR (KBr pellet): 1761 (CO ester), 1704
(11e). IR (KBr pellet) 1765 (CO, ester), 1695 (CO) cm
.
ꢂ1
1
1
CO) cm . H-NMR (300 MHz ,CDCl ): d 7.35 (1H, d, J = 8.4,
H-NMR (300 MHz, CDCl ): d 7.35 (1H, d, J = 8.4, H ), 6.92
3 5
3
H ), 6.93 (1H, dd, J = 8.4 and 2.4 Hz, H ), 6.84 (1H, d, J = 2.4
5
6
Hz, H
8
4
), 4.00 (1H, dd, J = 5.7 and 2.1 Hz, H ), 3.1 (1H, dd,
Scheme 7. Numbering of the hydrogens and carbons in compounds 7, 11,
and 16.
J = 16.2 Hz and 2.4 Hz, H
.9 Hz, H b), 2.63 (4H ,m, H , H
0
10
3
a), 2.72 (1H, dd, J = 14 Hz and
5
H11
), 1.25 (3H, t, J = 7.5 Hz,
3
10
1
3
0
), 1.02 (3H, t, J = 6.4 Hz, H ). C-NMR (75 MHz, CDCl3)
11
0
d 207.2 (C-9 ), 172.68 (C-9), 166.24 (C-2), 152.41 (C-7), 151.5
0
0
(
C-8 ), 129.05 (C-5), 118.23 (C-6), 117.5 (C-4 ), 111.76 (C-8),
0
4
7
2
7.6 (C-4), 33.67 (C-3), 30.72 (C-10), 27.78 (C-10 ), 9.06 (C-11),
.49 (C-11 ). HRMS, m/z (CI, CH ): Calcd for C H O (M )
76.0998. Found 276.1015.
Butyric acid 4-butyryl-3,4-dihydrocoumarin-7-yl ester (11c).
0
+
4
15 16 5
ꢁ
ꢂ1
Mp 111–123 C. IR (KBr pellet):1765 (CO ester), 1706 (CO) cm
.
1
H-NMR (300 MHz, acetone-d
6 5
): d 7.58 (1H, d, J = 8.4, H ),
6
.93 (1H, dd, J = 8.4 and 2.4 Hz, H ), 6.80 (1H, dd, J = 2.4 Hz,
6
H ), 4.27(1H, dd, J = 5.1 and 2.7 Hz, H ), 3.1 (1H, dd, J = 16.2
8
4
Hz and 2.4 Hz, H
3
a), 2.72 (1H, dd, J = 14 Hz and 5.9 Hz,
H
3
b), 2.64 (2H, t, J10
0
,11
0
= 7.2, H10
0
), 2.50 (2H, t, J10,11 = 7.5,
H10), 1.69 (2H, sex, J10,11 = J11,12 = 7.5 Hz, H11), 1.44 (2H, sex,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

9
08
S. Shachan-Tov and A. A. Frimer
Vol 49
(
(
1H, dd, J = 8.4 and 2.4 Hz, H ), 6.831 (1H, d, J = 2.4 Hz, H ), 3.97
(1H, d, J7,5 = 2.4 Hz, H ), 6.74 (1H, dd, J = 8.4 Hz and 2.4 Hz,
6
8
7
1H, dd, J = 6 and 2.4 Hz, H ), 3.0 (1H, dd, J = 16.2 Hz and 1.4 Hz,
H ), 3.70 (3H, s, H9
0
), 3.59 (2H, s, H ), 2.71 (2H, t, J
= 7.5 Hz,
4
5
8
9,10
C-H
3
a), 2.70 (1H, dd, J = 15.6 Hz and 5.4 Hz, H
3
b), 2.56 (4H, m,
H
9
), 1.70 (2H, sex, J15,16 = J16,17 = 7.5 Hz, H16), 1.37–1.25 (12H,
13
H
10, H10
12
–H17
0
), 1.75 (2H, m, H11 ), 1.75 (2H, m ,H11), 1.28 (12H, m,
0
m, H10-H15), 0.955 (3H, t, J16,17 = 7.5 Hz, H17). C-NMR
(75 MHz, CDCl
153.41 (C-2), 122.70 (C-3 ), 119.28 (C-4), 111.39 (C-5), 107.19
(C-3), 98.22 (C-7), 52.28 (C-9 ), 34.30 (C-8) 31.83 (C-15), 29.43
(C-11, C-12, C-13), 28.36 (C-9), 26.51 (C-14), 25.51 (C-10),
4
22.80 (C-16), 14.24 (C-17). HRMS, m/z (CI, CH ): Calcd for
0
0
0
H
0
0
), 1.20 (12H, m, H12–H17), 0.87 (6H, m, H18 and H18 ).
3
) d 171.82 (C-8 ), 155.56 (C-6), 154.83 (C-7 ),
13
0
0
C-NMR (75 MHz, CDCl ) d 206.75 (C-9 ), 171.98 (C-9),
3
0
0
1
66.21 (C-2), 152.45 (C-7), 151.49 (C-8 ), 129.04 (C-5), 118.19
0
(
(
(
(
(
C-6), 117.39 (C-4 ), 111.74 (C-8) , 47.86 (C-4), 40.30
C-3), 34.40 (C-10 ), 31.94 (C-16, C-16 ), 30.69 (C-10), 29.40
C-13-C-15, C-11 -C-15 ) 24.93 (C-11), 23.45 (C-12), 22.76
C-17, C-17 ), 14.20 (C-18, C-18 ). HRMS, m/z (CI, CH ): Calcd
0
0
0
0
+
C H O (M ) 322.1988. Found 332.1981.
20 28 4
0
0
Ethyl (6-hydroxy-2-methylbenzofuran-3-yl)-acetate (16f).
Yield: 47%; yellow oil; R = 0.47 (50% hexane in ethyl acetate).
H-NMR (300 MHz, CDCl ): d 7.272 (1H, d, J = 8.41 Hz, H ),
6.917 (1H, d, J = 2.4 Hz, H ), 6.80 (1H, dd, J = 8.41 Hz and 2.1,
), 3.59 (3H, s, H ), 2.34 (2H, s,
4
+
C
29
H O
45 5
, MH ) 473.3267, obsd 473.3253
f
1
Preparation of hydroxybenzofurans 16a–c, e, and f. The
3
4
acetoxydihydrocoumarins (11a–c and e, 60 mg) were dissolved
in 5 mL of methanol (for 16a–c, e) or ethanol (16f) containing
five to eight drops of hydrochloric acid. The reaction mixture
was stirred at r.t. for 12 h and quenched by the addition of
aqueous sodium bicarbonate solution (10 mL). The reaction
mixture was then extracted with chloroform, dried over
anhydrous Na SO , and evaporated to dryness at reduced
7
H ), 4.10 (2H, q, J = 7.2 Hz, H9
0
5
9
13
H ), 1.19 (3H, t, J = 7.2 Hz, H
0
). C-NMR (75 MHz, CDCl ) d
8
10
3
0
0
170.73 (C-8 ), 155.17 (C-6), 155.4 (C-7 ), 150.55 (C-2), 122
(C-3 ), 119.34 (C-4), 111.54 (C-5), 108.2 (C-3), 97.6 (C-7), 60.61
(C-9 ), 13.92 (C-10 ), 11.29 (C-9).
0
0
0
2
4
pressure to yield the desired product. These compounds are
essentially unknown. The only related compounds we have been
able to locate in the literature are ethyl 4,6-dimethoxy-2-methyl-
Acknowledgments. The authors thank Milon Sprecher for his
assistance in mechanistic elucidation. This article is based in part
on the M.Sc. Thesis of Sharona Shachan-Tov, Bar Ilan
University, January 2007. The authors gratefully acknowledge
the kind and generous support of The Israel Science Foundation
3
-benzofuranacetate and its 2,5-dimethyl analog [9].
Methyl (6-hydroxy-2-methylbenzofuran-3-yl)-acetate (16a).
Yield: 58%; white oily solid; R = 0.41 (50% hexane in ethyl
f
(Grants Number 437/06)—founded by The Israel Academy of
1
acetate). H-NMR (300 MHz ,CDCl
Hz, H ), 6.84 (1H, d, J = 2.1 Hz, H
Hz and 2.1 Hz, H ), 3.7 (3H, s, H
3H, s, H9). C-NMR (75 MHz, CDCl ) d170.72 (C-8 ),
54.72 (C-6), 153.34 (C-7 ), 151.53 (C-2), 122.5 (C-3 ), 118.97
3
): d 7.23 (1H, d, J = 8.41
Sciences and Humanities—and The Ethel and David Resnick
Chair in Active Oxygen Chemistry at Bar Ilan University.
4
7
), 6.70 (1H, dd, J = 8.41
0
), 3.59 (2H, s, H ), 2.38
5
9
8
13
0
(
1
(
3
0
0
REFERENCES AND NOTES
0
C-4), 111.47 (C-5), 107.28 (C-3), 98.15 (C-7), 52.45 (C-9 ),
[1] (a) Naya, K.; Takai, K.; Nakanishi, M.; Omura, K. Chem Lett
2
4
9.78 (C-8), 13.92 (C-9). HRMS, m/z (CI, CH ): Calcd for
+
1977, 1179; (b) Diyasena, M. N. C.; Sotheeswaran, S.; Surendrakumar,
S.; Balasubramanian, S.; Bokel, M.; Kraus, W. J Chem Soc Perkin Trans
C H O , (M ) 220.0746. Found 220.0746.
12 12 4
Methyl (6-hydroxy-2-ethylbenzofuran-3-yl)-acetate (16b).
Yield: 47%; yellow oil; R = 0.47 (50% hexane in ethyl
acetate). H-NMR (300 MHz, CDCl ): d 7.252 (1H, d, J = 8.1
Hz, H ), 6.859 (1H, d, J5,7 = 2.1 Hz, H ), 6.7 (1H, dd, J = 8.41
Hz and 2.1 Hz, H ), 3.68 (3H, s, H ), 3.58 (2H, s, H ), 2.73
1, 1985, 1807; (c) Engler, T. A.; LaTessa, K. O.; Iyengar, R.; Chai, W.;
f
Agrios, K. Bioorg Med Chem 1996, 4, 1755; (d) Dai, J. R.; Hallock, Y.
F.; Cardellina, J. H.; Boyd, M. J Nat Prod 1998, 61, 351; (e) Lin Y-L,
Chang, Y.-Y.; Kuo, Y. -H.; Shiao, M. -S. J Nat Prod 2002, 65, 745; (f)
Zhang, J.; Zhang, Y.; Zhang, Y.; Herndon, J. W. Tetrahedron 2003, 59,
1
3
4
7
0
5
9
8
5609; (g) Chen, Y.; Wei, X.; Xie, H.; Deng, H. J Nat Prod 2008, 71,
(
2H, q, J9 = 7.5 Hz, H ), 1.28 (3H, q, J
= 7.5 Hz, H10).
,10
9
9,10
0
1
3
929; (h) Dat, N. T.; Jin, X.; Lee, K.; Hong, Y.-S.; Kim, Y. H.; Lee, J. J.
J Nat Prod 2009, 72, 39.
C-NMR (75 MHz, CDCl
54.76 (C-7 ), 153.3 (C-2), 122.70 (C-3 ), 119.37(C-4), 111.37
3
) d 171.8 (C-8 ), 156.46 (C-6),
0
0
1
(
[2] (a) De Luca, L.; Nieddu, G.; Porcheddu, A.; Giacomelli, G.
0
C-5), 106.47 (C-3), 99.20 (C-7), 52.18 (C-9 ), 29.65 (C-8),
Curr Med Chem 2009, 16, 1; (b) Greve, S.; Friedrechsen, W. In: Progress
in Heterocyclic Chemistry; Gribble, G. W.; Gilchrist, T. L., Eds.;
Pergamon: Oxford, 2000; Vol. 12, p 134.
1
9.86 (C-9), 12.70 (C-10). HRMS, m/z (CI, CH ): Calcd for
4
+
C H O (M ) 234.0892. Found 234.0863.
13 14 4
[3] Murray, R. D. H.; Medez, J.; Brown, S. A. The Natural Coumar-
Methyl (6-hydroxy-2-n-propylbenzofuran-3-yl)-acetate (16c).
Yield: 47%; yellow oil; R = 0.51 (50% hexane in ethyl acetate).
H-NMR (300 MHz, CDCl ): d 7.27 (1H, d, J = 8.4 Hz, H ), 6.92
ins: Occurrence, Chemistry and Biochemistry, Wiley: New York, 1982.
[4] (a) Sun, W.-C.; Gee, K. R.; Haugland, R. P. Bioorg Med Chem
Lett 1998, 8, 3107; (b) Oyamada, J.; Jia, C.; Fujiwara, Y.; Kitamura, T.
Chem Lett 2002, 380; (c) See also Gunnewegh et al. Ref. 6 below.
f
1
3
4
(
H
H
1H, d, J7,5 = 2.1 Hz, H ), 6.7 (1H, dd, J = 8.1 Hz and 2.1 Hz,
7
5
), 3.69 (3H, s, H
), 1.70 (2H, sex, J9,10 = J10,11 = 7.2 Hz, H10), 0.955 (3H, t,
9 8
0
), 3.58 (2H, s, H ), 2.64 (2H, t, J9,10 = 7.2 Hz,
[5] (a) Frimer, A. A.; Aljadeff, G.; Gilinsky-Sharon, P. Israel J
9
Chem, 1986, 26, 39; (b) Frimer, A. A.; Strul, G.; Hameiri-Buch, J.; Got-
tlieb, H. E. Free Rad Biol Med, 1996, 20, 843; (c) Afri, M.; Gottlieb, H.
E.; Frimer, A. A.; Free Rad Biol Med 2002, 32, 605.
13
J
10,11 = 7.2 Hz, H11). C-NMR (75 MHz, CDCl
3
) d 171.22
0
0
0
(C-8 ), 155.25 (C-6), 154.75 (C-7 ), 153.23 (C-2), 122.66 (C-3 ),
[6] Gunnewegh, E. A.; Hoefnagel, A. J.; Downing, R. S.; van
1
19.15 (C-4), 111.30 (C-5), 107.28 (C-3), 98.12 (C-7), 52.09
Bekkum, H. Recueil Trav Chim Pays-Bas 1996, 115, 226.
0
(C-9 ), 29.70 (C-8), 28.23 (C-9), 21.50 (C-10) ,13.65 (C-11).
[
[
7] Lawson, A. J Chem Soc 1957, 144.
8] Cf. Sinha, N. K.; Sarkhel, B. K.; Srivastava, J. N. Indian J
+
HRMS, m/z (CI, CH
4 16 4
): Calcd for C14H O (M ) 248.1049.
Found 248.1068.
Chem, B, 1986, 25B, 640.
Methyl (6-hydroxy-2-nonylbenzofuran-3-yl)-acetate (16e).
[9] Cf. Birch, H. F.; Flynn, D. G.; Robertson, A. Curd, F. H.
JChem Soc 1936, 1834.
Yield: 50%; yellow oil; R = 0.59 (50% hexane in ethyl acetate).
f
1
[10] Cf. Molyneux, R. J.; Jurd, L. Aust J Chem 1974, 27, 2697.
3 4
H-NMR (300 MHz, CDCl ): d 7.26 (1H, d, J = 8.4 Hz, H ), 6.89
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet