Application of Baylis-Hillman methodology in the synthesis of coumarin derivatives

Article abstract of DOI:10.1081/SCC-120018937

A general, chemoselective approach to 3-substituted coumarins via Baylis-Hillman reactions of O-benzylated salicylaldehyde precursors has been demonstrated. Competitive cyclization to chromene derivatives is inhibited by conjugate addition of benzylamine or piperidine to the α,β-unsaturated ester intermediates.

Full text of DOI:10.1081/SCC-120018937

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Application of Baylis–Hillman Methodology in the
Synthesis of Coumarin Derivatives
Prof. Perry T. Kaye a & M. A. Musa a
a Department of Chemistry, Rhodes University, Grahamstown, Republic of South Africa
Published online: 17 Aug 2006.
To cite this article: Prof. Perry T. Kaye & M. A. Musa (2003) Application of Baylis–Hillman Methodology in the Synthesis of
Coumarin Derivatives, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 33:10, 1755-1770
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 10, pp. 1755–1770, 2003
Application of Baylis–Hillman Methodology
in the Synthesis of Coumarin Derivatives
*
Perry T. Kaye and M. A. Musa
Department of Chemistry, Rhodes University,
Grahamstown, Republic of South Africa
ABSTRACT
A general, chemoselective approach to 3-substituted coumarins via
Baylis–Hillman reactions of O-benzylated salicylaldehyde precursors
has been demonstrated. Competitive cyclization to chromene deriva-
tives is inhibited by conjugate addition of benzylamine or piperidine
to the a,b-unsaturated ester intermediates.
Key Words: Coumarins; Baylis–Hillman reaction; Synthesis.
Coumarins (2H-1-benzopyran-2-ones) are widely distributed in
nature,[1] and many are known to exhibit pharmacological activity.
These include the anti-coagulant, dicoumarol,[2] the antibiotics, novobio-
cin and chlorobiocin,[3] and the calanolides A and B, which have been
shown to inhibit HIV-1 replication in vitro.[4] We have previously demon-
*Correspondence: Prof. Perry T. Kaye, Department of Chemistry, Rhodes
University, Grahamstown, 6140 Republic of South Africa; Fax: 27 46 6225109;
E-mail: p.kaye@ru.ac.za.
1755
DOI: 10.1081/SCC-120018937
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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1756
Kaye and Musa
Scheme 1.
strated the utility of the Baylis–Hillman reaction in the construction of
benzannulated heterocycles, such as indolizines[5] and quinolines.[6]
However, earlier attempts to use this approach to access 2H-1-chromenes
from salicylaldehyde precursors afforded complex mixtures of chromene
and coumarin derivatives[7,8] via putative Baylis–Hillman intermediates
(Sch. 1). Attention was subsequently focussed on the chemoselective
synthesis of 2H-1-chromenes[9] and 2H-1-thiochromenes[10] and, in this
communication, we now report the application of Baylis–Hillman
methodology in the preparation of 3-substituted coumarins.
The strategy adopted to inhibit the formation of chromene derivatives
(Path I; Sch. 1) involved three phases, viz., (i) protection of the salicyl-
aldehyde phenolic hydroxyl group; (ii) nucleophilic interception of the
electrophilic vinylic centre in the Baylis–Hillman product; and (iii) depro-
tection of the phenolic oxygen to permit cyclization to coumarins via
acyl substitution. Attempts to protect the phenolic hydroxyl group as
the O-silylated or O-acetylated derivatives had proved unsatisfactory,[11]
and it was decided to make use of O-benzylated analogues, as reported by
Drewes et al.[12] Consequently, the salicylaldehyde derivatives 1a–f (Sch. 2)
were treated with benzyl bromide in the presence of K2CO3 and NaI to
afford the corresponding benzyl ethers 2a–f in yields ranging from66 to
89%. The next phase involved treatment of the benzyl ethers 2a–f with
methyl acrylate 3 under Baylis–Hillman conditions. In order to optimize
yields, the reaction of 2-benzyloxybenzaldehyde 2a with methyl acrylate in
the presence of DABCO was investigated in some detail. The reagent and
catalyst concentrations and the solvent systemwere varied until, finally,
the required Baylis–Hillman product 4a was obtained in ca. 95% yield (as
1
determined by H NMR analysis of the crude reaction mixture). This
protocol was then applied to the synthesis of the Baylis–Hillman products
4a–f, which were obtained in isolated yields of 66–84%.
Drewes et al.[12] have reported conjugate addition of dimethylamine
to compound 4a, but we decided to use the less volatile amines, benzyl-
amine and piperidine, to effect protection of the olefinic moiety in com-

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Baylis–Hillman Methodology in Coumarin Synthesis
1757
Reagents. i, PhCH2Br, K2CO3, NaI; ii, DABCO, CDCl3; iii, PhCH2NH2, MeOH
or piperidine, THF; iv, H2, Pd-C, EtOH.
Scheme 2.
pounds 4a–f. The novel, conjugate addition products 5a–f and 6a–f were
isolated in moderate to good yield (55–87%) and fully characterized.
Selected systems (5a–d and 6a–d) were then subjected to hydrogenolysis
in the presence of 10% palladium-on-carbon catalyst. Fission of the
benzyl ether and spontaneous cyclization via acyl substitution afforded,
in each case, the expected 3-substituted coumarins 7a–d and 8a–d.
Somewhat surprisingly, the piperidinyl derivatives 8a–d were
accompanied by the corresponding de-aminated derivatives 9a–d in
yields ranging from9–21%.

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1758
Kaye and Musa
A possible explanation for the concomitant formation of the
3-methylcoumarins 9a–d lay in the cyclization and dehydration of
hydroxy intermediates of type 10 [arising fromin situ elimination of
piperidine (6 ! 4) or incomplete conjugate addition (4 ! 6)] (Sch. 3).
However, various attempts to effect reductive cyclization of compound
4a failed to yield the corresponding 3-methylcoumarin 9a. Thus,
(i) hydrogenolysis using 10% palladium-on-carbon catalyst in ethanol
yielded the phenolic product 11; (ii) use of the same reagents in the pre-
sence of 1,4-cyclohexadiene yielded the benzyl ether 12; and (iii) use of
ethanethiol and BF3–Et2O yielded the 3-substituted coumarin 13.
An alternative explanation for the formation of the 3-methylcoumarins
Reagents. i, H2, Pd-C, EtOH; ii, H2, Pd-C, 1,4-cyclohexadiene, EtOH; iii, EtSH,
BF3-Et2O
Scheme 3.

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Baylis–Hillman Methodology in Coumarin Synthesis
1759
9a–d, finds a possible precedent in a report by Weir et al.,[13] which
describes the reductive elimination of piperidine from allylic amine pre-
cursors, using triethylammonium formate as a reducing agent and 10%
palladium-on-carbon as the catalyst. The formation of non-terminal
alkenes as the dominant products, in their study, parallels the formation
of the 3-methylcoumarins 9a–d fromthe corresponding ‘‘allylic amines’’
8a–d. In fact, hydrogenolysis of the piperidino derivative 8a, (Sch. 2), in
the presence of 10% palladium-on-carbon catalyst, afforded 3-methyl-
coumarin 9a as the sole product.
EXPERIMENTAL
Infrared spectra were recorded on a Perkin Elmer Spectrum 2000 FT-
IR spectrometer. The 1H and 13C NMR spectra were recorded using
CDC3 solutions on a Bruker Avance 400 MHz NMR spectrometer and
are referenced using the solvent signals. Low-resolution mass spectra
were recorded on a Finnigan-Mat GCQ mass spectrometer; FAB mass
spectra were obtained on a MASPEC II systemand high-resolution mass
spectra on a VG70-SEQ double-focusing magnetic sector instrument
by Dr. P. Boshoff at the Mass Spectrometry Unit, Cape Technikon,
Cape Town.
The following compounds have been reported previously:- 2a
(79%)[14]; 2b (89%)[15]
;
2c (85%)[16]; 2e (71%)[17]; 2f (66%)[17]; 4a
(75%)[12]; 9a (20%)[18]; and 9d (9%).[18] Illustrative general synthetic
procedures and analytical data for new compounds prepared in this
study are as follows.
2-Benzyloxy-5-chlorobenzaldehyde 2d
A solution of 5-chlorosalicylaldehyde (4.9 g, 31 mmol), benzyl bro-
mide (3.72 mL, 31.3 mmol), anhydrous K2CO3 (26 g, 0.19 mol) and NaI
(28.2 g, 0.19 mol) in distilled acetone (100 mL) was boiled under reflux for
12 h. Water (50 mL) was then added and the aqueous layer extracted with
CHCl3 (2 Â 100 mL). The combined extracts were washed with satd. brine
and dried (anhyd. Na2SO4), filtered and concentrated in vacuo to give a
dark brown oil. Crystallization fromhexane afforded, as yellow crystals,
2-benzyloxy-5-chlorobenzaldehyde 2d, (5.15 g, 67%), m.p. 70–72ꢀC (from
hexane) (Found: Mþ, 246.04567. C14H11O235Cl requires M, 246.04476.);
ꢀmax (KBr)/cmÀ1 1680 (C¼O); ꢁH 5.18 (2H, s, OCH2Ph), 7.00 (1H, d,
Ar-H), 7.34–7.47 (6H, series of multiplets, Ar-H), 7.79 (1H, d, ArH) and

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1760
Kaye and Musa
10.47 (1H, s, CHO); ꢁC 71.0 (OCH2Ph), 114.8, 126.2, 126.8, 127.3, 128.0,
128.5, 128.8, 135.3, 135.6 and 159.4 (Ar-C) and 188.3 (C¼O); m/z 246
[Mþ (35Cl), 9.6%] and 91 (100).
Methyl 3-(2-benzyloxy-3-methoxyphenyl)-3-hydroxy-
2-methylenepropanoate 4b (General Procedure)
A
mixture of 2-benzyloxy-3-methoxybenzaldehyde 2b (1.21g,
5 mmol), methyl acrylate 3 (2.37 mL, 26.3 mmol) and DABCO (294 mg,
2.63 mmol) in CDCl3 (0.25 mL) was stirred in a stoppered reaction flask
for three weeks. The mixture was concentrated in vacuo to give a brown
oil, which was purified by flash chromatography [elution with hexane–
EtOAc (3:1)] to afford, as pale yellow oil, methyl 3-(2-benzyloxy-3-meth-
oxyphenyl )-3-hydroxy-2-methylenepropanoate 4b (1.34 g, 84%) (Found:
Mþ, 328.13079. C19H20O5 requires M, 328.13107.); ꢀmax (thin film)/cm-1
3501 (OH) and 1714 (C¼O); ꢁH 2.88 (1H, d, OH), 3.69 and 3.89 (6H,
2 Â s, 2 Â OCH3), 5.07 (2H, s, OCH2), 5.71 and 6.27 (2H, 2 Âs, C¼CH2),
5.86 (1H, d, CHOH) and 6.89–7.45 (8H, series of multiplets, Ar-H);
ꢁC 51.8 and 55.8 (2 Â OCH3), 67.7 (CHOH), 74.7 (OCH2), 112.1, 119.4,
124.1, 125.8, 128.0, 128.2, 128.4, 135.1, 137.6, 141.7, 145.3 and 152.5
(C¼CH2 and Ar-C) and 166.8 (C¼O); m/z 328 (Mþ, 9.7%) and 205 (100).
Methyl 3-(2-benzyloxy-3-ethoxyphenyl)-3-hydroxy-2-methylenepro-
panoate 4c as a pale yellow oil, (1.37 g, 80%). (Found: Mþ, 342.14677.
C20H22O5 requires M, 342.14672.); ꢀmax (thin film)/cmÀ1 3484 (OH) and
1720 (C¼O); ꢁH 1.47 (3H, t, CH2CH3), 2.93 (1H, d, OH), 3.69 (3H, s,
OCH3), 4.10 (2H, q, OCH2CH3), 5.10 (2H, s, OCH2Ph), 5.72 and 6.28
(2H, 2 Â s, C¼CH2) 5.87 (1H, d, CHOH) and 6.89–7.46 (8H, series of
multiplets, Ar-H); ꢁC 15.0 (OCH2CH3), 51.8 (OCH3), 64.3 (OCH2CH3),
68.0 (CHOH), 74.7 (OCH2Ph), 125.8 (C¼CH2), 113.2, 119.4, 124.1,
128.0, 128.35, 128.42, 135.2, 137.7, 141.7, 145.5 and 151.9 (C¼CH2 and
Ar-C) and 166.9 (C¼O); m/z 342 (Mþ, 15.6%) and 219 (100).
Methyl
3-(2-benzyloxy-3-chlorophenyl)-3-hydroxy-2-methylenepro-
panoate 4d as pale yellow oil (1.29 g, 78%). (Found: Mþ, 332.08243.
C18H17O435Cl requires M, 332.08154.); ꢀmax (thin film)/cmÀ1 3479 (OH)
and 1715 (C¼O); ꢁH 3.32 (1H, br s, OH), 3.73 (3H, s, OCH3), 5.05 (2H, s,
OCH2Ph), 5.66 and 6.29 (2H, 2 Â s, C¼CH2), 5.88 (1H, s, CHOH), 6.84
(1H, d, Ar-H) and 7.17–7.40 (7H, series of multiplets, Ar-H); ꢁC 52.0
(OCH3), 67.8 (CHOH), 70.5 (OCH2Ph), 126.4 (C¼CH2), 113.1, 126.2,
127.3, 127.8, 128.2, 128.5, 128.6, 131.5, 136.3, 140.7 and 154.2 (C¼CH2
and Ar-C) and 166.9 (C¼O); m/z 332 [Mþ(35Cl), 5.7%] and 209 (100).

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Baylis–Hillman Methodology in Coumarin Synthesis
1761
Methyl 3-(2-benzyloxy-5-bromophenyl)-3-hydroxy-2-methylenepro-
panoate 4e as pale yellow crystals (1.58 g, 84%), m.p. 114–116ꢀC.
(Found: Mþ, 376.02870. C18H17O479Br requires M, 376.03102.); ꢀmax
(KBr)/cmÀ1 3217 (OH) and 1716 (C¼O); ꢁH 3.32 (1H, br s, OH), 3.72
(3H, s, OCH3), 5.04 (2H, s, OCH2Ph), 5.65 and 6.28 (2H, 2 Â s, C¼CH2),
5.88 (1H, s, CHOH), 6.78 (1H, d, Ar-H), 7.30–7.39 (6H, series of multi-
plets, Ar-H) and 7.54 (1H, d, Ar-H); ꢁC 52.0 (OCH3), 67.7 (CHOH), 70.5
(OCH2Ph), 113.5, 113.7, 126.4, 127.3, 128.2, 128.6, 130.6, 131.5, 131.9,
136.2, 140.8 and 154.7 (C¼CH2 and Ar-C) and 166.9 (C¼O); m/z 376
[Mþ (79Br), 11.5%] and 255 (100).
Methyl 3-(2-benzyloxy-3,5-dibromophenyl)-3-hydroxy-2-methylenþe-
propanoate 4f as a pale yellow oil (1.50 g, 66%). (Found: M ,
453.94193. C18H16O479Br2 requires M, 453.94153.); ꢀmax (thin film)/cmÀ1
3479 (OH) and 1715 (C¼O); ꢁH 2.84 (1H, br s, OH) 3.69 (3H, s, OCH3),
5.07 (2H, d, OCH2Ph), 5.76 and 6.35 (2H, 2 Â s, C¼CH2), 5.81 (1H, d,
CHOH), 7.35–7.48 (6H, series of multiplets, Ar-H) and 7.68 (1H, d,
Ar-H); ꢁC 52.1 (OCH3), 67.2 (CHOH), 75.5 (OCH2Ph), 126.9
(C¼CH2), 117.7, 118.3, 128.3, 128.5, 128.6, 130.2, 135.6, 136.3, 138.5,
140.5 and 152.5 (C¼CH2 and Ar-C) and 166.4 (C¼O); m/z 454 [Mþ
(79Br2), 1.9%] and 333 (100).
Methyl 2-(benzylaminomethyl)-3-(2-benzyloxyphenyl)-
3-hydroxypropanoate 5a (General Procedure)
A mixture of methyl 3-(2-benzyloxyphenyl)-3-hydroxy-2-methylene-
propanoate 4a (0.6 g, 2 mmol) and benzylamine (0.22 mL, 2 mmol) in
methanol (4 mL) was stirred in a stoppered reaction flask for 3 days.
Excess benzylamine was evaporated in vacuo to give a yellow oil (0.80 g),
which was purified by preparative layer chromatography [elution with
hexane–MeOH–EtOAc (2:0.1:1)] to afford, as pale yellow crystals, methyl
2-(benzylaminomethyl)-3-(2-benzyloxyphenyl)-3-hydroxypropanoate 5a
(0.50 g, 62%), m.p. 94–96ꢀC (Found: MHþ, 406.201633. C25H27 NO4
requires Mþ1, 406.201834.); ꢀmax (KBr)/cmÀ1 3308 (OH) and 1720
(C¼O); ꢁH 2.54 (1H, dd, CHANHCH2Ph), 3.06–3.13 (2H, complex of
overlapping signals, CHCHBNHCH2Ph), 3.64 and 3.69 (2H, 2 Â d,
NCH2Ph), 3.75 (3H, s, OCH3), 5.13 (2H, 2 Â d, OCH2Ph), 5.77 (1H, m,
CHOH), 6.90–6.96 (2H, m, Ar-H) and 7.20–7.47 (12H, series of multiplets,
Ar-H); ꢁC 46.2 (CH2NHCH2Ph), 47.4 (CHCO2CH3), 51.9 (OCH3), 54.2
(CH2NHCH2Ph), 69.6 (OCH2Ph), 71.8 (CHOH), 111.3, 120.9, 126.8,
127.0, 127.2, 127.7, 128.1, 128.37, 128.42, 128.5, 131.7, 137.0, 139.1 and
154.5 (Ar-C) and 174.2 (C¼O); m/z 405 (Mþ, 0.1%) and 91 (100).

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1762
Kaye and Musa
Methyl 2-(benzylaminomethyl)-3-(2-benzyloxy-3-methoxyphenyl)-3-
hydroxypropanoate 5b as a pale yellow oil (0.76 g, 87%). (Found:
MHþ, 436.212314. C26H29O5N requires M þ 1, 436.212398.);
ꢀmax (thin film)/cmÀ1 3325 (OH) and 1732 (C¼O); ꢁH 2.48 (1H, dd,
CHANHCH2Ph), 3.04–3.12 (2H, complex of overlapping signals,
CHCHBNHCH2Ph), 3.65 (2H, s, CH2NHCH2Ph), 3.73 and 3.90 (6H,
2 Â s, OCH3), 4.89 and 5.22 (2H, 2 Â d, OCH2), 5.65 (1H, m, CHOH)
and 6.89–7.53 (13H, series of multiplets, Ar-H); ꢁC 46.1 (CH2NHCH2Ph),
48.1 (CHCO2CH3), 51.8 and 55.7 (2 Â OCH3), 54.1 (NHCH2Ph), 72.1
(CHOH), 74.5 (OCH2Ph), 111.2, 118.8, 123.9, 127.1, 127.9, 128.19,
128.24, 128.3, 128.4, 137.1, 137.5, 139.0, 143.8 and 152.3 (Ar-C) and
173.8 (C¼O); m/z 436 (Mþ, 17.3%) and 120 (100).
Methyl 2-(benzylaminomethyl)-3-(2-benzyloxy-3-ethoxyphenyl)-3-
hydroxypropanoate 5c as a pale yellow oil (0.64 g, 71%). (Found: MHþ,
450.228102. C27H31O5N requires M þ 1, 450.228048.); ꢀmax (thin
film)/cmÀ1 3323 (OH) and 1733 (C¼O); ꢁH 1.49 (3H, t, CH2CH3), 2.47
(1H, dd, CHANHCH2Ph), 3.06–3.10 (2H, m, CHCHBNHCH2Ph), 3.64
(2H, s, NHCH2Ph), 3.72 (3H, s, OCH3), 4.10 (2H, q, OCH2CH3), 4.89
and 5.24 (2H, 2 Â d, OCH2Ph), 5.64 (1H, s, CHOH) and 6.86–7.52
(13H, series of multiplets, Ar-H); ꢁC (400 MHz, CDCl3) 15.0
(OCH2CH3), 46.2 (CH2NHCH2Ph), 48.1 (CHCO2CH3), 51.9 (OCH3),
54.2 (NHCH2Ph), 64.1 (OCH2CH3), 72.2 (CHOH), 74.6 (OCH2Ph),
112.2, 118.7, 123.9, 127.2, 128.0, 128.28, 128.31, 128.46, 128.50, 137.2,
137.7, 139.1, 143.9 and 151.7 (Ar-C) and 174.0 (C¼O); m/z 450 (MHþ,
6.9%) and 91 (100%).
Methyl 2-(benzylaminomethyl)-3-(2-benzyloxy-5-chlorophenyl)-3-
hydroxypropanoate 5d as a yellow solid (0.61 g, 69%), m.p. 68–70ꢀC.
(Found: MHþ, 440.162907. C25H26O4N35Cl, requires: M þ 1,
440.162861.); ꢀmax (KBr)/cmÀ1 3298 (OH) and 1732 (C¼O); ꢁH 2.51
(1H, dd, CHANHCH2Ph), 3.05 (1H, dd, CHCH2NH), 3.14 (1H, m,
CHBNHCH2Ph), 3.68 (2H, s, NHCH2Ph), 3.74 (3H, s, OCH3), 5.06
(2H, 2 Â d, OCH2Ph), 5.72 (1H, d, CHOH) and 6.83–7.51 (13H, series
of multiplets, Ar-H); ꢁC 46.3 (CH2NHCH2Ph), 47.0 (CHCO2CH3), 52.0
(OCH3), 54.2 (CH2NH2CH2Ph), 70.0 (OCH2Ph), 71.5 (CHOH), 112.7,
126.3, 126.8, 127.3, 127.4, 127.8, 127.9, 128.2, 128.5, 128.6, 133.8, 136.5,
138.7 and 153.0 (Ar-C) and 173.8 (C¼O); m/z 440 [MHþ (35Cl), 1.8%]
and 91 (100).
Methyl
2-(benzylaminomethyl)-3-(2-benzyloxy-5-bromophenyl)-3-
hydroxypropanoate 5e as a yellow oil (0.61 g, 63%). (Found: MHþ,
484.112392. C25H26O4N79Br requires M þ 1, 484.112345.); ꢀmax (thin
film)/cmÀ1 3324 (OH) and 1732 (C¼O); ꢁH 2.53 (1H, dd,
CHANHCH2Ph), 3.07 (1H, dd, CHCH2NHCH2Ph), 3.16 (1H, ddd,

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Baylis–Hillman Methodology in Coumarin Synthesis
1763
CHBNHCH2Ph), 3.69 (2H, dd, NHCH2Ph), 3.75 (3H, s, OCH3), 5.08 (2H,
dd, OCH2Ph), 5.74 (1H, s, CHOH), 6.80 (1H, d, Ar-H), 7.27–7.44 (11H,
series of multiplets, Ar-H) and 7.69 (1H, d, Ar-H); ꢁC 46.3
(CH2NHCH2Ph), 47.0 (CHCO2CH3), 52.0 (OCH3), 54.2 (NHCH2Ph),
69.9 (OCH2Ph), 71.3 (CHOH), 113.2, 113.6, 126.7, 127.3, 127.9, 128.1,
128.4, 128.5, 130.1, 130.8, 134.1, 136.3, 138.7 and 153.5 (Ar-C) and 173.7
(C¼O); m/z 484 [MHþ (79Br), 3.0%] and 121 (100).
Methyl 2-(benzylaminomethyl)-3-(2-benzyloxy-3,5-dibromophenyl)-3-
hydroxypropanoate 5f as
a yellow oil (0.80 g, 71%). (Found:
MHþ, 562.022773. C25H25O4N79Br2, requires: M þ 1, 562.022856.);
ꢀmax (thin film)/cmÀ1 3419 (OH) and 1747 (C¼O); ꢁH 2.43 (1H,
dd, CHANHCH2Ph), 3.02 (1H, m, CHCH2NH), 3.14 (1H, dd,
CHBNHCH2Ph), 3.60 (2H, s, NHCH2Ph), 3.70 (3H, s, OCH3), 4.81
and 5.15 (2H, 2 Â d, OCH2Ph), 5.59 (1H, d, CHOH) and 7.27–7.57
(12H, series of multiplets, Ar-H); ꢁC 46.3 (CH2NHCH2Ph), 47.7
(CHCO2CH3), 52.1 (OCH3), 54.2 (NHCH2Ph), 72.1 (CHOH), 75.2
(OCH2Ph), 117.9, 118.3, 127.6, 128.3, 128.48, 128.54, 128.6, 128.7,
130.0, 134.8, 136.1, 138.2, 140.6 and 151.3 (Ar-C) and 173.1 (C¼O); m/z
562 [MHþ (79Br2 ), 1.2%] and 92 (100).
Methyl 3-(2-benzyloxyphenyl)-3-hydroxy-
2-(piperidinomethyl)propanoate 6a (General Procedure)
A mixture of methyl 3-(2-benzyloxyphenyl)-3-hydroxy-2-methylene-
propanoate 4a (0.56 g, 2 mmol) and piperidine (0.50 mL) in THF (5 mL)
was stirred in a stoppered reaction flask for 3 days. Excess piperidine was
evaporated in vacuo to give a yellow oil (0.77 g), which was purified by
preparative layer chromatography [elution with CHCl3-EtOAc (3:1)] to
afford, as pale yellow crystals, methyl 3-(2-benzyloxyphenyl )-3-hydroxy-
2-(piperidinomethyl )propanoate 6a (0.61 g, 80%), m.p 102–104ꢀC.
(Found: Mþ, 383.21036. C23H29NO4 requires M, 383.20966.); ꢀmax
(KBr)/cmÀ1 3145 (OH) and 1722 (C¼O); ꢁH 1.43 (2H, m,
CH2CH2CH2N), 1.58 (4H, m, CH2CH2N), 2.41 and 2.51 (4H, 2 Â br s,
CH2CH2N), 2.69 (1H, d, CHANHCH2Ph), 3.00 (1H, t, CHCH2NH), 3.26
(1H, m, CHBNHCH2Ph), 3.40 (3H, s, OCH3), 5.05 and 5.10 (2H, 2 Â d,
OCH2Ph), 5.38 (1H, d, CHOH), 6.90 (1H, d, Ar-H), 6.94 (1H, t, Ar-H)
and 7.18–7.37 (7H, series of multiplets, Ar-H); ꢁC 23.9, 25.8 and 54.8
(CH2CH2CH2N), 47.3 (CHCO2CH3), 51.5 (OCH3), 60.0 (CH2CH2N),
70.2 (OCH2Ph), 72.9 (CHOH), 112.0, 120.9, 127.3, 127.7, 128.41,
128.43, 128.7, 130.5, 137.2 and 155.9 (Ar-C) and 172.6 ( C¼O); m/z
383 (Mþ, 1.0%) and 91 (100).

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1764
Methyl
Kaye and Musa
3-(2-benzyloxy-3-methoxyphenyl )-3-hydroxy-2-(piperidino-
methyl )propanoate 6b as a pale yellow oil (0.46 g, 55%). (Found: Mþ,
413.22071. C24H31NO5 requires M, 413.22022; ꢁH 1.42 (2H, m,
CH2CH2CH2N), 1.57 (4H, m, CH2CH2N), 2.37 and 2.52 (4H, 2 Â br s,
CH2CH2N), 2.64 and 2.96 (2H, 2 Â dd, CH2NHCH2Ph), 3.21 (1H, m,
CHCO2CH3), 3.41 and 3.88 (6H, 2 Â s, OCH3), 4.97 and 5.13 (2H,
2 Â d, OCH2Ph), 5.31 (1H, d, CHOH), 6.85 (1H, dd, Ar-H), 7.02–7.38
(5H, series of multiplets, Ar-H) and 7.52 (2H, d, Ar-H); ꢁC 23.9, 25.9 and
54.7 (CH2CH2CH2N), 47.5 (CHCO2CH3), 51.5 and 55.8 (2 Â OCH3),
60.4 (CHCH2N), 73.3 (CHOH), 74.8 (OCH2Ph), 111.8, 120.2, 124.0,
127.6, 127.9, 128.2, 136.0, 138.2, 145.7 and 152.7 (Ar-C) and 172.4
(C¼O); m/z 413 (Mþ, 1.3%) and 99 (100).
Methyl 3-(2-benzyloxy-3-ethoxyphenyl )-3-hydroxy-2-(piperidino-
methyl)propanoate 6c as a pale yellow oil (0.50 g, 58%). (Found:
Mþ, 427.23545. C25H33NO5 requires M, 427.23587.); ꢁH 1.47 (5H, over-
lapping signals, OCH2CH3 and CH2CH2CH2N), 1.54 (4H, m,
CH2CH2N), 2.37 (2H, br s, CH2CH2N), 2.53 (2H, m, CH2CH2N), 2.64
and 2.99 (2H, dd, CHCH2N), 3.21 (1H, m, CHCO2CH3), 3.40 (3H, s,
OCH3), 4.06 (2H, q, OCH2CH3), 4.98 and 5.13 (2H, 2 Â d, OCH2Ph),
5.30 (1H, d, CHOH) and 6.84–7.53 (8H, series of multiplets, Ar-H); ꢁC
15.0 (OCH2CH3), 23.9, 25.9 and 54.7 (CH2CH2CH2N), 47.4
(CHCO2CH3), 51.5 (OCH3), 60.3 (CH2N), 64.2 (OCH2CH3), 73.4
(CHOH), 74.8 (OCH2Ph), 113.0, 120.1, 123.9, 127.6, 128.1, 128.2,
136.1, 138.3, 146.0 and 152.0 (Ar-C) and 172.5 (C¼O); m/z 427 (Mþ,
1.2%) and 99 (100).
Methyl
3-(2-benzyloxy-5-chlorophenyl )-3-hydroxy-2-(piperidino-
methyl)propanoate 6d as a pale yellow oil (0.67 g, 63%). (Found: Mþ,
417.17090. C23H28NO435Cl requires M, 417.17069.); ꢁH 1.43 (2H, m,
CH2CH2CH2N), 1.58 (4 H, m, CH2CH2N), 2.40 and 2.52 (4H, 2 Â br
s, CH2CH2N), 2.64 and 2.99 (2H, 2 Â dd, CHCH2N), 3.11 (1H, m,
CHCO2CH3), 3.42 (3H, s, OCH3), 5.04 (2H, 2 Â d, OCH2Ph), 5.41
(1H, d, CHOH), 6.80 (1H, d, Ar-H) and 7.13–7.46 (7H, series of
multiplets, Ar-H); ꢁC 23.9, 25.9 and 54.8 (CH2CH2CH2N), 47.3
(CHCO2CH3), 51.5 (OCH3), 59.9 (CH2CH2N), 70.5 (OCH2Ph), 71.9
(CHOH), 113.2, 126.1, 127.2, 127.9, 128.2, 128.4, 128.5, 132.8, 136.7
and 154.3 (Ar-C) and 172.2 (C¼O); m/z 417 [Mþ (35Cl), 1.2%]
and 98 (100).
Methyl
3-(2-benzyloxy-5-bromophenyl )-3-hydroxy-2-(piperidino-
methyl )propanoate 6e as a pale yellow oil (0.60 g, 62%). (Found: Mþ,
461.12015. C23H28NO479Br requires M, 461.12017.); ꢀmax (thin
film)/cmÀ1 3419 (OH) and 1732 (C¼O); ꢁH 1.43 (2H, m,
CH2CH2CH2N), 1.57 (4H, m, CH2CH2N), 2.39 and 2.51 (4H, 2 Â br s,

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Baylis–Hillman Methodology in Coumarin Synthesis
1765
CH2CH2N), 2.64 (1H, m, CHCHAN), 2.99 (1H, t, CHCHBN), 3.10 (1H,
m, CHCO2CH3), 3.42 (3H, s, OCH3), 5.03 (2H, q, 2 Â d, OCH2Ph), 5.41
(1H, d, CHOH), 6.75 (1H, d, Ar-H), 7.27–7.42 (6H, series of multiplets,
Ar-H) and 7.53 (1H, d, Ar-H); ꢁC 23.9, 25.8 and 54.7 (CH2CH2CH2N),
47.3 (CHCO2CH3), 51.5 (OCH3), 59.8 (CHCH2N), 70.4 (OCH2Ph), 71.8
(CHOH), 113.4, 113.6, 127.1, 127.9, 128.5, 131.15, 131.17, 133.2, 136.6,
154.7 (Ar-C) and 172.1 ( C¼O); m/z 462 [Mþ (79Br), 3.4%] and 99 (100).
Methyl
3-(2-benzyloxy-3,5-dibromophenyl)-3-hydroxy-2-(piperidino-
methyl)propanoate 6f as a pale yellow oil (0.73 g, 65%). (Found: Mþ,
539.02614. C23H27NO479Br2 requires M, 539.03068.); ꢁH 1.44 (2H, m,
CH2CH2CH2N), 1.56 (4H, m, CH2CH2N), 2.38 and 2.56 (4H, 2 Â br s,
CH2CH2N), 2.63 (1H, d, CHCHAN), 3.02 (2H, overlapping multiplets,
CHCHBN), 3.42 (3H, s, OCH3), 4.91 and 5.12 (2H, 2 Â d, OCH2Ph), 5.24
(1H, d, CHOH), 7.33–7.53 (5H, series of multiplets, Ar-H),7.59 (1H, d,
Ar-H) and 7.64 (1H, d, Ar-H); ꢁC 23.8, 25.8 and 54.8 (CH2CH2CH2N),
47.3 (CHCO2CH3), 51.8 (OCH3), 60.4 (CHCH2N), 73.1 (CHOH), 75.5
(OCH2Ph), 117.6, 118.4, 127.9, 128.1, 128.4, 130.9, 135.1, 136.8, 139.6
and 152.8 (Ar-C) and 171.5 ( C¼O); m/z 539 [Mþ (79Br2), 0.9%]
and 91 (100).
3-(Benzylaminomethyl)coumarin 7a (General Procedure)
A mixture of methyl 2-(benzylaminomethyl)-3-(2-benzyloxyphenyl)-
3-hydroxypropanoate 5a (490 mg, 1.21 mmol) and pre-equilibrated 10%
Pd–C catalyst (84 mg) in 95% EtOH (6.7 mL) was hydrogenated at room
temperature and atmospheric pressure. (Hydrogen absorption ceased
after the uptake of one equivalent of hydrogen.) The mixture was filtered
and the solvent removed in vacuo to give the crude mixture (360 mg) as a
pale yellow oil, which was purified using preparative layer chromatogra-
phy [on silica; elution with CHCl3–EtOAc (3 : 1)] to afford, as a pale
yellow solid, 3-(benzylaminomethyl )coumarin 7a (170 mg, 53%), m.p.
70–74ꢀC. (Found: Mþ, 265.10796. C17H15O2N requires M, 265.11028.);
ꢀmax (KBr)/cmÀ1 3323 (N-H) and 1713 (C¼O); ꢁH 1.95 (1H, br, s, NH),
3.76 (2H, d, 10-CH2), 3.86 (2H, s, CH2Ph), 7.23–7.51 (9H, series of
overlapping signals, Ar-H) and 7.72 (1H, s, 4-H); ꢁC 48.3 and 53.2
(2 Â CH2), 116.4, 119.2, 124.3, 127.0, 127.4, 127.5, 128.1, 128.4, 130.9,
139.1, 139.7 and 153.1 (Ar-C) and 161.4 (C¼O); m/z 265 (Mþ, 0.9%)
and 174 (100).
3-(Benzylaminomethyl)-8-methoxycoumarin 7b as a pale yellow oil
(190 mg, 50%). (Found: Mþ, 295.11855. C18H17O3N requires M,
295.12084.); ꢀmax (KBr)/cmÀ1 3394 (NH) and 1714 (C¼O); ꢁH 1.88
(1H, br s, NH), 3.76 (2H, d, 10-CH2), 3.84 (2H, s, CH2Ph), 3.95 (3H, s,

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1766
Kaye and Musa
OCH3), 7.04 (2H, d, Ar-H), 7.17–7.36 (6H, series of multiplets, Ar-H)
and 7.69 (1H, d, 4-H); ꢁC 48.4 and 53.2 (2 Â CH2), 56.3 (OCH3), 113.0,
119.1, 120.0, 124.2, 127.1, 127.7, 128.2, 128.5, 139.3, 139.7, 142.9 and
147.1 (Ar-C) and 160.9 (C¼O); m/z (FAB) 296 (MHþ, 100%).
3-(Benzylaminomethyl)-8-ethoxycoumarin 7c as a pale yellow solid
(250 mg, 66%), m.p. 98–102ꢀC. (Found: Mþ, 309.13418. C19H19O3N
requires M, 309.13649.); ꢀmax(KBr)/cmÀ1 3300 (NH) and 1712 (C¼O);
ꢁH 1.49 (3H, t, OCH2CH3), 2.00 (1H, br s, 3.75 (2H, d, 10-CH2), 3.84 (2H,
s, CH2Ph), 4.20 (2H, q, OCH2CH3), 7.01–7.36 (8H, series of multiplets,
Ar-H) and 7.68 (1H, s, 4-H); ꢁC 14.7 (OCH2CH3), 48.4 and 53.1
(2 Â CH2), 64.9 (OCH2CH3), 114.3, 119.0, 120.0, 124.2, 127.0, 127.5,
128.1, 128.4, 139.3, 139.8, 143.1 and 146.4 (Ar-C) and 161.0 (C¼O);
m/z (FAB) 310 (MHþ, 100%).
3-(Benzylaminomethyl)-6-chlorocoumarin 7d as a yellow solid (190mg,
50%), m.p. 106–110ꢀC. (Found: Mþ, 298.06240. C17H14O3N35Cl requires
M À 1, 298.06348.); ꢀmax (KBr)/cmÀ1 3322 (NH) and 1719 (C¼O); ꢁH
1.82 (1H, br s, NH), 3.74 (2H, d, 10-CH2), 3.85 (2H, s, CH2Ph),
7.23–7.45 (8H, series of multiplets, Ar-H) and 7.69 (1H, s, 4-H); ꢁC
48.1 and 53.2 (2 Â CH2), 117.8, 120.3, 126.7, 127.1, 128.0, 128.4, 128.8,
129.5, 130.8, 137.7, 139.6 and 151.4 (Ar-C) and 160.7 (C¼O); m/z (FAB)
300 [MHþ (35Cl), 96.1%] and 91 (100).
3-(Piperidinomethyl)coumarin 8a and 3-methylcoumarin 9a
(General Procedure)
A mixture of methyl 3-(2-benzyloxyphenyl)-3-hydroxy-2-(piperidino-
methyl)propanoate 5a, (466 mg, 1.22 mmol) and pre-equilibrated 10% Pd-
C catalyst (84 mg) in absolute EtOH (6.7 mL) was hydrogenated at room
temperature and atmospheric pressure for 6 h. The resulting mixture was
filtered and the solvent removed from the filtrate in vacuo to give a pale
yellow oil (380 mg), which was purified by preparative layer chromato-
graphy [on silica; elution with CHCl3–EtOAc (3:1)] to afford two pro-
ducts:
(i) 3-(Piperidinomethly)coumarin 8a as a brown solid (150 mg, 51%),
m.p. 66–68ꢀC. (Found: Mþ, 243.12588. C15H17O2N requires M,
243.12593.); ꢀmax (KBr)/cmÀ1 1723 (C¼O); ꢁH 1.46 (2H, m,
CH2CH2CH2N), 1.59 (4H, m, CH2CH2N), 2.48 (4H, br s, CH2CH2N),
3.42 (2H, d, J 0.4 Hz, 10-CH2), 7.23–7.49 (4H, series of multiplets, Ar-H)
and 7.78 (1H, s, Ar-H); ꢁC 24.1, 25.9 and 54.7 (CH2CH2CH2N), 56.9
(10-CH2), 116.3, 119.3, 124.2, 126.0, 127.5, 130.7, 139.4 and 152.9 (Ar-
C) and 161.5 (C¼O); m/z 243 (Mþ, 62.9%) and 200 (100); and
(ii) 3-Methylcoumarin 9a as a pale yellow solid (40 mg, 20%).[18]

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Baylis–Hillman Methodology in Coumarin Synthesis
1767
The general procedure was followed. Work-up and chromatography
afforded:
(i) 8-Methoxy-3-(piperidinomethyl)coumarin 8b as a pale yellow oil
(150 mg, 45%). (Found: Mþ, 273.13684. C16H19O3N requires M,
273.13649.); ꢀmax (thin film)/cmÀ1 1714 (C¼O); ꢁH 1.45 (2H, m,
CH2CH2CH2N), 1.60 (4H, m, CH2CH2N), 2.47 (4H, t, CH2CH2N),
3.42 (2H, d, 10-CH2), 3.93 (3H, s, OCH3), 7.02 (1H, d, Ar-H), 7.06
(1H, d, Ar-H), 7.18 (1H, t, Ar-H) and 7.77 (1H, s, Ar-H); ꢁC 24.1, 26.0
and 54.7 (CH2CH2CH2N), 56.2 (OCH3), 56.9 (10-CH2), 112.7, 119.1,
120.1, 124.1, 126.3, 139.7, 142.7 and 147.0 (Ar-C) and 161.1 (C¼O);
m/z 273 (Mþ, 91.2%) and 230 (100); and
(ii) 8-Methoxy-3-methylcoumarin 9b as a grey solid, (22 mg, 9.5%),
m.p. 68–72ꢀC. (Found: Mþ, 190.06299. C11H10O3 requires M,
190.06299.); ꢀmax (KBr)/cmÀ1 1716 (C¼O); ꢁH 2.20 (3H, s, CH3), 3.94
(3H, s, OCH3), 6.99 (2H, t, Ar-H), 7.16 (1H, t, Ar-H) and 7.48 (1H, s, 4-
H); ꢁC 17.2 (CH3), 56.2 (OCH3), 112.4, 118.4, 120.2, 124.1, 126.1, 139.3,
142.9 and 147.0 (Ar-C) and 161.6 (C¼O); m/z 190 (Mþ, 100%).
The general procedure was followed. Work-up and chromatography
afforded:
(i) 8-Ethoxy-3-(piperidinomethyl)coumarin 8c as a pale yellow oil
(170 mg, 49%). (Found: Mþ, 287.15293. C17H21O3N requires M,
287.15214.); ꢀmax (thin film)/cmÀ1 1714 (C¼O); ꢁH 1.47 (5H, m,
OCH2CH3 and CH2CH2CH2N), 1.62 (4H, m, CH2CH2N), 2.49 (4H, t,
CH2CH2N), 3.45 (2H, s, 10-CH2), 4.17 (2H, q, OCH2CH3), 7.02 and 7.05
(2H, 2 Â d, Ar-H), 7.15 (1H, t, Ar-H) and 7.77 (1H, s, 4-H); ꢁC 14.8
(OCH2CH3), 24.2, 26.0 and 54.7 (CH2CH2CH2N), 56.9 (10-CH2),
65.0 (OCH2CH3), 114.3, 119.1, 120.3, 124.1, 126.3, 139.8, 143.1 and
146.4 (Ar-C) and 161.3 (C¼O); m/z 287 (Mþ, 74.4%) and 176 (100); and
(ii) 8-Ethoxy-3-methylcoumarin 9c as a pale yellow oil (35mg, 14%).
(Found: Mþ, 204.07884. C12H12O3 requires M, 204.07864.); ꢀmax (thin
film)/cmÀ1 1714 (C¼O); ꢁH 1.47 (3H, t, CH2CH3), 2.19 (3H, d, 3-CH3),
4.16 (2H, q, OCH2CH3), 6.95 and 6.98 (2H, 2 Â dd, Ar-H), 7.13 (1H, t,
Ar-H) and 7.47 (1H, dd, Ar-H); ꢁC 14.7 (OCH2CH3), 17.1 (3-CH3),
64.8 (OCH2CH3), 113.7, 118.4, 120.3, 124.0, 125.9, 139.4, 143.1 and
146.3 (Ar-C) and 161.8 (C¼O); m/z 204 (Mþ, 59.1%) and 176 (100).
The general procedure was followed. Work-up and chromatography
afforded:
(i) 6-chloro-3-(1-piperidinylmethyl)coumarin 8d, as a pale yellow
solid (205 mg, 61%), m.p. 116–118ꢀC. (Found: Mþ, 277.08708.
C15H16O2N35Cl requires M, 277.08696.);
ꢀ
max(KBr)/cmÀ1 1724
(C¼O); ꢁH 1.47 (2H, m, CH2CH2CH2N), 1.63 (4H, m, CH2CH2N),
2.48 (4H, t, CH2CH2N), 3.42 (2H, d, 10-CH2), 7.25 (1H, t, Ar-H),

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1768
Kaye and Musa
7.40 and 7.42 (2H, 2 Â dd, Ar-H), 7.48 (1H, d, Ar-H) and 7.72 (1H, s,
4-H); ꢁC 24.2, 26.1 and 54.8 (CH2CH2CH2N), 57.0 (10-CH2), 117.8,
120.6, 126.8, 127.8, 129.5, 130.7, 138.0 and 151.4 (Ar-C) and 161.0
(C¼O); m/z 277 [Mþ (35Cl), 52.3%] and 234 (100); and
(ii) 6-chloro-3-methylcoumarin 9d, as a pale yellow solid (22 mg,
9%).[18]
Methyl 3-(2-hydroxyphenyl)-2-methylpropanoate 11
A mixture of methyl 3-(2-benzyloxyphenyl)-3-hydroxy-2-methylene-
propanoate 4a (0.36 g, 1.2 mmol) and pre-equilibrated 10% Pd-C catalyst
(84 mg) in absolute EtOH (6.7 mL) was hydrogenated at room tempera-
ture and atmospheric pressure for 6 h. The mixture was filtered and the
solvent removed from the filtrate in vacuo to give a yellow oil (204 mg),
which was purified using flash chromatography [elution with hexane–
EtOAc (3:1.5)] followed by extraction with acetone to afford, as a pale
yellow oil, methyl 3-(2-hydroxyphenyl )-2-methylpropanoate 11 (186 mg,
80%). (Found: Mþ, 194.09567. C11H14O3 requires M, 194.09429.); ꢀmax
(thin film)/cmÀ1 3396 (OH) and 1709 (C¼O); ꢁH 1.26 (3H, d, 2-CH3), 2.70
(1H, dd, CHAH), 2.86 (1H, m, CHCH3), 3.01 (1H, dd, CHBH), 3.65 (3H,
s, OCH3), 6.84 (2H, m, Ar-H), 6.92 (1H, br s, ArOH), and 7.05–7.11 (2H,
m, Ar-H); ꢁC 17.9 (CHCH3), 33.5 (CH2), 40.7 (CHCH3), 52.1 (OCH3),
116.8, 120.5, 125.8, 127.9, 131.2 and 154.2 (Ar-C) and 178.7 (C¼O); m/z
194 (Mþ, 11.5%) and 162 (100).
Methyl 3-(2-benzyloxyphenyl)-2-methylpropenoate 12
A solution of methyl 3-(2-benzyloxyphenyl)-3-hydroxy-2-methylene-
propanoate 4a (0.30 g, 1 mmol) in ethanol (4 mL) was stirred, under N2, in
a two-necked, round-bottomed flask, immersed in a water bath at 25ꢀC.
Pre-equilibrated 10% Pd-C catalyst (84 mg) was then added, followed by
1,4-cyclohexadiene (0.94 mL, 10 mmol). The resulting mixture was boiled
under reflux for 2 h and filtered through celite. The solid residue was
washed with ethanol (ca. 5 mL), and the filtrate and washings were
combined and evaporated in vacuo to afford a crude product (0.25 g),
which was purified using preparative layer chromatography [elution with
hexane–EtOAc (3:1)] to afford, as a yellow oil, methyl 3-(2-benzyloxy-
phenyl )-2-methylpropenoate 12 (50 mg, 18%). (Found: Mþ, 282.12610.
C18H18O3 requires M, 282.12559.); ꢀmax (thin film)/cmÀ1 1711 (C¼O); ꢁH
2.08/2.12[19] (3H, 2 Â d, J 1.6 and 1.6 Hz, CH3C¼C), 3.59/3.82 (3H, 2 Â s,
OCH3), 5.10/5.14 (2H, 2 Â s, OCH2OPh), 6.90–7.44 (9H, series of multi-
plets, Ar-H ) and 7.95 (1H, br s, ArCH¼C)[20]; m/z 282 (Mþ, 15.4%) and
92 (100).

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Baylis–Hillman Methodology in Coumarin Synthesis
3-(Ethylsulfanylmethyl)coumarin 13
1769
To a solution of methyl 3-(2-benzyloxyphenyl)-3-hydroxy-2-methy-
lenepropanoate 4a (0.22 g, 0.72 mmol) in EtSH (2 mL) was added boron
trifluoride etherate (1 mL, 8 mmol), and the resulting mixture was stirred
at room temperature for 40 min. The mixture was poured into water and
extracted with Et2O. The combined organic extracts were washed with
satd. brine, dried (anhyd. Na2SO4), filtered and concentrated in vacuo
to afford an oil (0.54 g), which was purified using preparative layer
chromatography [elution with hexane–EtOAc (3:1)] to afford, as a
yellow solid, 3-(ethylsulfanylmethyl)coumarin 13 (15 mg, 10%), m.p.
68–72ꢀC (Found: Mþ, 220.05715. C12H12O2S requires M, 220.05580.);
ꢀmax (KBr)/cmÀ1 1720 (C¼O); ꢁH 1.29 (3H, t, SCH2CH3), 2.58 (2H, q,
SCH2CH3), 3.66 (2H, s, CH2S), 7.27 (1H, d, Ar-H), 7.33 (1H, d, Ar-H),
7.48 (2H, d, Ar-H) and 7.71 (1H, s, Ar-H); ꢁC 14.4 (SCH2CH3), 26.3
and 30.8 (CH2SCH2CH3) 116.6, 119.2, 124.4, 126.4, 127.5, 131.2, 139.4
and 153.3 (Ar-C) and 161.1 (C¼O); m/z (FAB) 220 (Mþ, 37%) and
160 (100).
ACKNOWLEDGMENT
The authors thank the National Research Foundation (NRF) and
Rhodes University for generous financial support.
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(1:1.7) of the geometric isomers.
20. The COSY spectrumindicates weak coupling to the allylic methyl
protons and to an aromatic proton.
Received in the USA August 16, 2002