A convenient general synthesis of 3-substituted 2H-chromene derivatives

Article abstract of DOI:10.1039/b201827f

Reactions of 2-hydroxybenzaldehydes and 2-hydroxy-1-naphthaldehydes with various activated alkenes under Baylis-Hillman conditions have been shown to proceed with regioselective cyclisation to afford the corresponding 3-substituted chromene derivatives. In some cases competitive dimerisation of the alkene component was observed, and direct dimerisation in the absence of the aldehyde has been explored.

Full text of DOI:10.1039/b201827f

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A convenient general synthesis of 3-substituted 2H-chromene
derivatives
Perry T Kaye * and Xolani W. Nocanda
1
Department of Chemistry, Rhodes University, Grahamstown, 6140, South Africa.
E-mail: P.Kaye@ru.ac.za
Received (in Cambridge, UK) 20th February 2002, Accepted 2nd April 2002
First published as an Advance Article on the web 26th April 2002
Reactions of 2-hydroxybenzaldehydes and 2-hydroxy-1-naphthaldehydes with various activated alkenes under
Baylis–Hillman conditions have been shown to proceed with regioselective cyclisation to afford the corresponding
3-substituted chromene derivatives. In some cases competitive dimerisation of the alkene component was observed,
and direct dimerisation in the absence of the aldehyde has been explored.
the phenolic oxygen at the vinylic centre (path I) provides access
Introduction
to chromene derivatives, nucleophilic substitution at the acyl
centre of the ester group (path II) leads to coumarin derivatives.
Inhibition of the latter pathway was successfully achieved by
replacing the acrylic esters used in the initial study15 with vinyl
ketones (R4 = COMe, COEt; Scheme 2), while careful optim-
isation of the reaction conditions permitted isolation of
chromene derivatives in up to 87% yield.10 After examining
various solvent systems for the reaction of salicylaldehyde with
MVK, it was found that use of a vigorously stirred, hetero-
geneous mixture of chloroform and water, as the solvent sys-
tem, and use of 0.8 equivalents of DABCO gave the best result;
further improvement in the yield was achieved by adding more
MVK at intervals during the course of the reaction.10 The
generality of the Baylis–Hillman approach to chromenes has
subsequently been demonstrated by extending: i, the range of
activated alkenes to include acrylaldehyde, acrylonitrile, phenyl
vinyl sulfone and phenyl ethenesulfonate and ii, the range
of 2-hydroxybenzaldehyde substrates to include 2-hydroxy-1-
naphthaldehyde.
Many naturally-occurring pharmacologically active com-
pounds contain the 2H-1-benzopyran (2H-chromene) nucleus.
Notable amongst these are the 2,2-dimethylchromene deriv-
atives isolated from propolis, a resinous product known for over
2000 years for its healing properties.1 Calonolide F, isolated
from Calophyllum tesymannii,2 also contains the 2,2-dimethyl-
chromene moiety and exhibits anti-HIV activity, while synthetic
analogues have been shown to possess antihypertensive3 and
anti-ischaemic4 activity.
Various protocols have been developed for the synthesis
of 2H-chromenes,5 and new methods of accessing these
important compounds continue to be reported. These include:
the intramolecular cyclisation of Wittig intermediates;6 the
microwave-assisted reaction of salicylaldehyde with enamines;7
the iodine-catalysed cyclocondensation of 2-hydroxybenz-
aldehydes with 2,2-dimethoxypropane8 and ring-closing olefin
metathesis.9 In a preliminary communication10 we recently
described a novel and convenient synthesis of 3-acyl-2H-
chromenes involving the Baylis–Hillman reaction of 2-hydroxy-
benzaldehydes with methyl vinyl ketone (MVK) in the presence
of 1,4-diazabicyclo[2.2.2]octane (DABCO). DeBoer11 has
prepared 2H-chromenes by reacting salicylaldehyde (as the
phenoxide ion) with activated alkenes in an approach which
presumably involves conjugate addition, followed by an aldol-
type cyclisation. However, there is ample evidence, which will
be reported elsewhere,12 that the DABCO-catalysed reactions
follow a Baylis–Hillman pathway.13,14
Treatment of salicylaldeyde 2a (R1 = R2 = R3 = H; Scheme
2) with acrylaldehyde, phenyl vinyl sulfone, phenyl ethene-
sulfonate and acrylonitrile under the established conditions
afforded the 3-substituted chromenes 6i–l, respectively, in yields
ranging from 54 to 70%. Use of phenyl vinyl ketone 8, how-
ever, gave 3-benzoyl-2H-chromene 6m in disappointingly low
yield (10%), the major product being the ketone dimer 9a
(Scheme 3), while reaction of 2-hydroxy-3,5-dinitrobenz-
aldehyde 2t with MVK gave none of the expected chromene but
afforded, instead, the MVK dimer 9b as the sole product.
Electron-withdrawing substituents are expected to activate the
aldehyde to nucleophilic attack by a zwitterionic intermediate
in the rate-determining step of the Baylis–Hillman reaction16
but, in the case of 2-hydroxy-3,5-dinitrobenzaldehyde 2t, none
of the expected product was obtained. The ortho- and para-
nitro substituents presumably enhance the acidity of the phen-
olic hydroxy group to the extent that protonation of DABCO
occurs with consequent inhibition of its catalytic activity. In
the reaction of 3,5-dibromo-2-hydroxybenzaldehyde 2h with
MVK, the chroman-4-ol 5h was isolated in 53% yield together
with the expected chromene 6h (29%; Scheme 4), a result which
is clearly consistent with the addition–elimination sequence
proposed in Scheme 2. Although the chroman-4-ol 5h contains
two stereogenic centres, the apparent absence of signal doub-
ling in both the 1H- and 13C NMR spectra suggests the presence
of only one diastereomer (as an enantiomeric pair), formulated
Results and discussion
Previous attempts to prepare 2H-chromenes chemoselectively
via the cyclisation of 2-hydroxybenzaldehyde-derived Baylis–
Hillman products had proved unsuccessful affording, instead,
complex mixtures of coumarin and chromene derivatives
(Scheme 1).15 Thus, while conjugate addition involving attack of
Scheme 1
1318
J. Chem. Soc., Perkin Trans. 1, 2002, 1318–1323
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b201827f

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Scheme 4 Reagents and conditions: i, DABCO, CHCl3–H2O, rt, 7 d.
Fig. 1 Diastereofacial selectivity during enolate protonation (showing
one enantiomeric series).
Scheme 2 Reagents and conditions: i, DABCO, CHCl3–H2O, rt.
as the cis-isomer cis-5h (Fig. 1) on the basis of the small vicinal
coupling (J3,4 = 3.5 Hz) between the 3- and 4-methine protons.
In a trans-diequatorial arrangement of the 3- and 4-substit-
uents, the methine protons would be diaxial and could be
expected to exhibit much larger coupling constants. The
observed stereochemistry is attributed to protonation at the less
hindered face of the enolate intermediate 10.
the corresponding 3-substituted benzo[f]chromenes 6n–s in
yields ranging from 17 to 67% (Table 1); in some cases, the
benzochromanol precursors 5q–s were isolated in low yields
(2–4%) together with the corresponding benzo[f]chromenes 6.
In an earlier study in our laboratories, Robinson13,15 had
isolated the 4-substituted chromane 13 (Scheme 5) from a
reaction between salicylaldeyde and methyl acrylate under
Baylis–Hillman conditions. The formation of this product was
attributed to in situ conjugate addition of the “Baylis–Hillman
Reaction of 2-hydroxy-1-naphthaldehyde 2n (instead of
salicylaldehyde) with the series of activated alkenes 3 afforded
Scheme 3 Reagents and conditions: i, HCHO, Me2NH2Cl, HCl, EtOH, reflux, 2 h; ii, heat; iii, DABCO, CHCl3–H2O, rt, 7 d.
J. Chem. Soc., Perkin Trans. 1, 2002, 1318–1323
1319

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Table 1 Data for 3-substituted chromene derivatives 6a–s (Scheme 2)
HRMS data: m/z, Mϩ
Compd.
R1
R2
R3
R4
Yielda(%)
Found
Mol. formula
Required
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
6q
6r
6s
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
NO2
Cl
Br
Br
H
H
H
H
H
OMe
OEt
H
H
H
Br
H
H
H
H
H
H
H
H
H
H
COMe
COEt
COMe
COMe
COMe
COMe
COMe
COMe
CHO
SO2Ph
SO3Ph
CN
COPh
COMe
COEt
CHO
81
83
79
84
54
56
174.0671
188.0835
204.0788
218.0945
219.0516
208.0296
251.9795
329.8881
160.0532
272.0510
288.0444
157.0520
236.0835
224.0832
238.0994
210.0678
322.0674
338.0617
207.0675
C11H10O2
C12H12O2
C12H12O3
C13H14O3
C11H9NO4
C11H935ClO2
C11H979BrO2
C11H8O279Br2
C10H8O2
C15H12O3S
C15H12O4S
C10H7NO
C16H12O2
C15H12O2
C16H14O2
C14H10O2
C19H14O3S
C19H14O4S
C14H9NO
174.0681
188.0837
204.0786
218.0943
219.0532
208.0291
251.9786
329.8891
160.0524
272.0506
288.0455
157.0527
236.0837
224.0837
238.1005
210.0681
322.0664
338.0613
207.0684
87
29(53)b
54
70
60
H
H
65
10c
67
–(CH)4–
–(CH)4–
–(CH)4–
–(CH)4–
–(CH)4–
–(CH)4–
58
17
SO2Ph
SO3Ph
CN
20(2)b
61(4)b
50(2)b
H
a Chromatographed material. b Yield of corresponding chroman-4-ol intermediate. c The dimer 9a was isolated as the major product (65%; see
Scheme 3).
Scheme 6 Reagents and conditions: i, DABCO or DBU, CHCl3.
substrates (Scheme 6). The dimeric products 9a–h were obtained
in low to moderate yields, methyl and ethyl acrylate requiring
the use of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)21 to effect
dimerisation, albeit in very low yield (10% and 5% respectively).
In summary, it is evident that the application of Baylis–
Hillman methodology provides convenient, general and rel-
atively efficient access to 3-substituted 2H-chromenes, and that
the alkene dimers, observed in some cases as competition pro-
ducts, can generally be obtained by direct dimerisation using an
appropriate catalyst.
Experimental
Melting points were determined using a Kofler hot-stage
apparatus and are uncorrected. NMR spectra were recorded
on Bruker AMX400 or AVANCE 400 MHz spectrometers at
303 K in CDCl3 or DMSO-d6, and calibrated using solvent
signals. Infrared spectra were recorded on a Perkin Elmer
FT-IR spectrum 2000 spectrometer, using hexachlorobutadiene
Scheme 5 Reagents and conditions: i, DABCO, CHCl3, rt.
or nujol mulls, thin films or NaCl discs. Low-resolution (EI)
zwitterion” 11 to methyl 6-chlorochromene-3-carboxylate 12,
mass spectra were obtained on a Finnigan-Mat GCQ mass
the latter acting as a Michael acceptor. In an attempt to demon-
spectrometer and high-resolution (EI) mass spectra on a VG70-
strate such transformations, 3-acetyl-2H-chromene 6a was
treated with several activated alkenes 3b–e in the presence of
DABCO but, in each case, the sole product was the correspond-
SEQ double-focusing magnetic sector spectrometer (Cape
Technikon Mass Spectrometry unit). Elemental (HRMS)
analytical and other data for the chromene derivatives 6a–s
ing alkene dimer 9 (Scheme 5). Dimerisation of activated
are detailed in Table 1. The general synthetic procedures are
alkenes in the presence of DABCO has been reported by
illustrated by the following examples.
Drewes et al.17 and Basavaia et al.,18 while other researchers
have effected similar dimerisation using phosphine19 and rho-
3-Acetyl-2H-chromene 6a
dium complex20 catalysts. The formation of such dimers as
competition products in our own studies prompted further
examination of this reaction using the activated alkenes 3a–h as
A mixture of salicylaldehyde 2a (1.0 cm3, 9.6 mmol), methyl
vinyl ketone (1.2 cm3, 14 mmol) and DABCO (0.86 g, 7.7 mmol)
1320
J. Chem. Soc., Perkin Trans. 1, 2002, 1318–1323

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in CHCl3 (1.0 cm3) and H2O (1.0 cm3) was stirred vigorously
under N2 in a stoppered flask at room temperature. After
stirring the reaction mixture for 24 hours, additional methyl
vinyl ketone (0.4 cm3, 5 mmol) and DABCO (0.29 g, 2.6 mmol)
were added and stirring was continued for 24 hours before
adding further quantities of methyl vinyl ketone (0.20 cm3,
2.4 mmol) and DABCO (0.10 g, 0.85 mmol) and stirring for a
further 72 hours. Flash chromatography of the resulting mix-
ture [on silica; elution with hexane–EtOAc (4 : 1)] afforded, as
yellow crystals, 3-acetyl-2H-chromene 6a, mp 39–40 ЊC (lit.11
50–53 ЊC); νmax (hexachlorobutadiene mull/cmϪ1) 1655 (CO);
δH (400 MHz; CDCl3) 2.39 (3H, s, CH3), 4.99 (2H, s, CH2), 6.83
(1H, d, J 7.1, ArH), 6.95–7.23 (3H, series of multiplets, ArH)
and 7.29 (1H, s, 4-H); δC (100 MHz; CDCl3) 25.0 (CH3), 64.2
(CH2), 116.3, 120.7, 121.8, 129.1, 130.8, 132.4, 133.9 and 155.6
3-Phenylsulfonyl-3,4-dihydro-2H-benzo[f]chromen-4-ol 5q and
3-phenylsulfonyl-2H-benzo[f]-chromene 6q
A mixture of 2-hydroxy-1-naphthaldehyde 2n (1.0 g, 5.8 mmol),
phenyl vinyl sulfone (1.5 g, 8.7 mmol) and DABCO (0.52 g,
4.7 mmol) in CHCl3 (1.0 cm3) and water (1.0 cm3) was stirred
vigorously at room temperature under N2. After stirring for
24 hours, phenyl vinyl sulfone (0.5 g, 2.9 mmol) and DABCO
(0.17 g, 1.6 mmol) were added and stirring was continued for
72 hours; thereafter, additional phenyl vinyl sulfone (0.25 g,
1.5 mmol) and DABCO (0.06 g, 0.5 mmol) were added and
stirring was continued for a further 72 hours. Flash chrom-
atography of the resulting mixture [on silica; elution with
hexane–EtOAc (4 : 1)] afforded two products:
i) 3-Phenylsulfonyl-2H-benzo[f]chromene 6q. Dark yellow
(ArC and C᎐CH) and 195.9 (CO); m/z 174 (Mϩ, 62%) and 131
᎐
crystals, mp 186–188 ЊC; νmax (chloroform/cmϪ1) 3020 (C᎐C–H)
᎐
(100).
and 2918 (CH2); δH (400 MHz; CDCl3) 4.97 (2H, d, J 0.8, CH2),
7.10 (1H, d, J 8.8, ArH), 7.21–7.80 (10H, series of multiplets,
ArH) and 7.88 (1H, s, 4-H); δC (100 MHz; CDCl3) 63.1 (CH2),
113.4, 117.2, 121.3, 124.8, 127.8, 128.1, 128.3, 128.8, 129.3,
3-Acetyl-6,8-dibromochroman-4-ol 5h and 3-acetyl-6,8-dibromo-
2H-chromene 6h
3,5-Dibromo-2-hydroxybenzaldehyde 2h (1.0 g, 3.6 mmol) was
reacted with methyl vinyl ketone (0.44 cm3, 5.4 mmol) and
DABCO (0.32 g, 2.9 mmol) in chloroform (1.0 cm3) and water
(1.0 cm3) following the general procedure. Work-up and flash
chromatography gave two products:
129.5, 130.7, 133.6, 133.7, 139.7 and 153.6 (ArC and C᎐CH);
᎐
m/z 322 (Mϩ, 66%) and 180 (100).
ii) 3-Phenylsulfonyl-3,4-dihydro-2H-benzo[f]chromen-4-ol 5q.
An oil, (Found: Mϩ, 340.0769. C19H16O4S requires: M,
340.0779); νmax (hexachlorobutadiene mull/cmϪ1) 3023 (OH);
δH (400 MHz; CDCl3) 3.28 (1H, d, J 3.5, OH), 3.63 (1H, dt,
J 3.0 and 11.8, 3-H), 4.55 (1H, m, 2-H), 4.65 (1H, t, J 11.8,
2-H), 5.83 (1H, s, 4-H), 7.00 (1H, d, J 9.0, ArH), 7.37–8.07
(10H, series of multiplets, ArH); δC (100 MHz; CDCl3) 59.0
(CH2), 59.5 (CH), 63.2 (CH), 113.5, 118.2, 121.8, 124.2, 127.6,
128.5, 128.6, 129.3, 129.6, 131.3, 132.3, 134.5, 138.6 and 151.5
(ArC); m/z 340 (Mϩ, 90%) and 169 (100).
i) 3-Acetyl-6,8-dibromo-2H-chromene 6h. Yellow crystals, mp
74–75 ЊC; νmax (hexachlorobutadiene mull/cmϪ1) 1666 (CO); δH
(400 MHz; CDCl3) 2.40 (3H, s, CH3), 5.10 (2H, s, CH2), 7.16
(1H, s, 4-H), 7.23 (1H, d, J 2.2, ArH) and 7.58 (1H, d, J 2.2,
ArH); δC (100 MHz; CDCl3) 25.2 (CH3), 65.3 (CH2), 111.2,
113.5, 123.2, 130.5, 131.5, 132.1, 137.4 and 151.4 (ArC and
CH᎐C) and 195.3 (CO); m/z 332 (Mϩ, 64.3%) and 289 (100).
᎐
ii) 3-Acetyl-6,8-dibromochroman-4-ol 5h. Pale yellow crystals,
mp 132–134 ЊC (Found: Mϩ, 347.8990. C11H10O379Br2 requires:
M, 347.8997); νmax (hexachlorobutadiene mull/cmϪ1) 3444 (OH)
and 1696 (CO); δH (400 MHz; CDCl3), 2.34 (3H, s, CH3), 3.02
(1H, d, J 5.3, OH), 3.04 (1H, m, 3-H), 4.43 (1H, dd, J 11.4 and
13.8, 2-H), 4.60 (1H, dd, J 3.5 and 11.4, 2-H), 5.04 (1H, m, 4-
H), 7.44 (1H, s, ArH) and 7.60 (1H, s, ArH); δC (100 MHz;
CDCl3) 29.0 (CH3), 50.6 (CH), 63.2 (CH2), 64.2 (CH), 111.7,
112.9, 126.1, 131.8, 135.7 and 150.1 (ArC) and 206.8 (CO); m/z
350 (Mϩ, 30%) and 289 (100).
3-Methyleneheptane-2,6-dione 9b
A mixture of methyl vinyl ketone (1.0 cm3, 12 mmol) and
DABCO (0.45 g, 4.0 mmol) in chloroform (1.0 cm3) was stirred
at room temperature in a stoppered reaction flask for 7 days.
The resulting mixture was purified by flash chromatography
[elution with hexane–EtOAc (3 : 2)] to afford, as a dark yellow
oil, 3-methyleneheptane-2,6-dione 9b, νmax (thin film/cmϪ1) 1709
and 1670 (CO); δH (400 MHz; CDCl3) 2.02 (3H, s, CH3), 2.22
(3H, s, CH3), 2.43 (2H, m, CH2), 2.47 (2H, m, CH2), 5.73 and
5.93 (2H, 2 × s, C᎐CH ); δ (100 MHz; CDCl ) 25.0 (CH ), 25.6
᎐
2
C
3
3
(CH ), 29.6 (CH ), 42.2 (CH ), 125.9 (C᎐CH ), 147.5 (C᎐CH ),
᎐
᎐
2
2
3
2
2
3-Benzoyl-2H-chromene 6m and 1,5-diphenyl-2-methylene-
pentane-1,5-dione 9a
199.2 (CO) and 207.5 (CO).
Compounds 6a, 6c, 6f and 6g,23 6i,11 6l,23 6m,11 9a,24 9b,25 9c,26
9d and 9e27 and 9h18 have also been reported by other
researchers; compounds 6b, 6d, 6e and 6h were reported in our
preliminary communication.10 Analytical data for the other,
new chromene derivatives 6 and dimeric products 9 are as
follows.
Salicylaldehyde 2a (1.0 cm3, 9.6 mmol) was reacted with phenyl
vinyl ketone 822 (1.9 g, 14 mmol) and DABCO (0.86 g, 7.7
mmol) in chloroform (1.0 cm3) and water (1.0 cm3) following
the general procedure. Work-up and flash chromatography gave
two products:
i) 3-Benzoyl-2H-chromene 6m. Yellow oil; νmax (hexachloro-
butadiene mull/cmϪ1) 1750 (CO); δH (400 MHz; CDCl3) 5.16
(2H, s, CH2), 6.91–7.73 (10H, series of multiplets, ArH and
4-H); δC (100 MHz; CDCl3) 65.3 (CH2), 116.4, 121.0, 121.8,
128.4, 129.0, 129.3, 129.8, 132.0, 132.5, 137.0, 137.6 and 155.6
3-Phenylsulfonyl-2H-chromene 6j
White crystals, mp 122–123 ЊC; νmax (hexachlorobutadiene mull/
cmϪ1) 3077 and 3058 (C᎐C–H) and 1311 (S᎐O); δ (400 MHz;
᎐
᎐
H
CDCl3) 4.85 (2H, s, CH2), 6.68 (1H, d, J 16.6, ArH) and 6.81–
7.92 (9H, series of multiplets, ArH and 4-H); δC (100 MHz;
CDCl3) 63.11 (CH2), 116.3, 119.9, 122.3, 127.9, 129.4, 129.5,
(ArC and C᎐CH) and 194.1 (CO); m/z 236 (Mϩ, 24.0%) and 105
᎐
(100).
131.1, 132.6, 132.8, 133.8, 139.3 and 154.1 (ArC and CH᎐C);
᎐
m/z 272 (Mϩ, 91%) and 131 (100).
ii) 1,5-Diphenyl-2-methylenepentane-1,5-dione 9a. White crys-
tals, mp 52 ЊC (lit.24 57–58 ЊC); νmax (in chloroform/cmϪ1) 1684
and 1650 (2 × CO); δH (400 MHz; CDCl3) 2.91 (2H, t, J 7.2,
Phenyl 2H-chromene-3-sulfonate 6k
CH ), 3.24 (2H, t, J 2.2, CH ), 5.67 and 5.96 (2H, 2 × s, C᎐CH )
and 7.40–7.98 (10H, series of multiplets, ArH); δC (100 MHz;
White crystals, mp 82–84 ЊC; νmax (hexachlorobutadiene mull/
cmϪ1) 3065 (C᎐C–H), 2922 (CH ) and 1487 (S᎐O); δ
᎐
2
2
2
᎐
᎐
2
H
CDCl3) 27.3 (CH2), 37.2 (CH2), 127.3, 128.1, 128.2, 128.6,
(400 MHz; CDCl3) 5.21 (2H, d, J 1.0, CH2), 6.92 (1H, d, J 8.1,
ArH) and 6.97–7.37 (9H, series of multiplets, ArH and 4-H);
δC (100 MHz; CDCl3) 63.3 (CH2), 116.7, 119.7, 122.3, 122.5,
129.5, 132.2, 133.1, 136.7, 137.7 and 146.7 (ArC and C᎐CH ),
᎐
2
198.1 (CO) and 199.2 (CO).
J. Chem. Soc., Perkin Trans. 1, 2002, 1318–1323
1321

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125.1, 127.4, 129.6, 129.9, 133.3, 135.8, 149.4 and 154.7 (ArC
i) 3-Cyano-2H-benzo[f]chromene 6s. Yellow crystals, mp
120–122 ЊC; νmax (hexachlorobutadiene mull/cmϪ1) 2210 (CN);
δH (400 MHz; CDCl3) 4.88 (2H, s, CH2), 7.09 (1H, d, J 8.8,
ArH), 7.43–7.80 (4H, series of multiplets, ArH), 7.85 (1H, s,
4-H) and 7.86 (1H, d, J 8.8, ArH); δC (100 MHz; CDCl3) 64.2
(CH2), 100.3, 113.8, 117.0, 117.3, 121.0, 124.8, 128.2, 128.9,
129.5, 129.9, 133.5 and 135.3 (ArC) and 154.0 (CN); m/z 207
(Mϩ, 73%) and 206 (100).
and C᎐CH); m/z 288 (Mϩ, 69%) and 131 (100).
᎐
3-Acetyl-2H-benzo[f]chromene 6n
Yellow crystals, mp 122–124 ЊC; νmax (hexachlorobutadiene
mull/cmϪ1) 1660 (CO); δH (400 MHz; CDCl3) 2.51 (3H, s, CH3),
5.09 (2H, s, CH2), 7.10 (1H, d, J 8.6, ArH), 7.41–7.99 (6H,
series of multiplets, ArH) and 8.01 (1H, s, 4-H); δC (100 MHz;
CDCl3) 25.1 (CH3), 64.0 (CH2), 113.9, 117.6, 120.9, 124.4,
127.7, 128.4, 128.9, 129.4, 130.1, 130.8, 133.2 and 155.2 (ArC
ii) 3-Cyano-3,4-dihydro-2H-benzo[f]chroman-4-ol 5s. An oil
(Found: Mϩ, 225.0788. C14H11NO2 requires: M, 225.0790);
νmax (hexachlorobutadiene mull/cmϪ1) 3421 (OH) and 2249
(CN); δH (400 MHz; CDCl3) 2.75 (1H, br s, OH), 3.28 (1H, dt,
J 11.8 and 3.6, 3-H), 4.42 (1H, m, 2-H), 4.53 (1H, dd, J 10.6 and
3.6, 2-H), 5.5 (1H, d, J 1.6, 4-H), 7.05 (1H, d, J 9.0, ArH), 7.41–
7.79 (4H, series of multiplets, ArH) and 8.02 (1H, d, J 8.5,
ArH); δC (100 MHz; CDCl3) 32.3 (CH), 59.7 (CH), 60.7 (CH2),
112.4, 116.8, 118.4, 121.6, 124.4, 127.8, 128.8, 129.4, 131.5 and
132.2 (ArC) and 151.6 (CN); m/z 225 (Mϩ, 66%) and 172 (100).
and C᎐C) and 195.6 (CO); m/z 224 (Mϩ, 63%) and 181 (100).
᎐
3-Propanoyl-2H-benzo[f]chromene 6o
Yellow crystals, mp 88–90 ЊC; νmax (chloroform/cmϪ1) 1654
(CO); δH (400 MHz; CDCl3) 1.22 (3H, t, J 7.2, CH3), 2.89 (2H,
q, J 7.2, CH2), 5.10 (2H, s, CH2), 7.10 (1H, d, J 8.8, ArH), 7.42–
7.99 (5H, series of multiplets, ArH) and 8.02 (1H, s, 4-H);
δC (100 MHz; CDCl3) 8.6 (CH3), 30.4 (CH2), 64.3 (CH2), 114.0,
117.6, 120.9, 124.3, 127.6, 127.9, 128.8, 128.9, 129.4, 130.8,
133.0 and 155.1 (ArC and C᎐CH) and 198.6 (CO); m/z 238
2,4-Bis(phenylsulfonyl)but-1-ene 9f
᎐
(Mϩ, 95%) and 181 (100).
A colourless oil (Found: Mϩ Ϫ PhSO2, 195.04830. C16H16O4S2
requires: M Ϫ PhSO2, 195.04798); νmax (thin film/cmϪ1) 3038
2H-Benzo[f]chromene-3-carbaldehyde 6p
(C᎐C–H) and 2929 (CH ); δ (400 MHz; CDCl3) 2.64 (2H, m,
᎐
2
H
Yellow crystals, mp 144–146 ЊC; νmax (chloroform/cmϪ1) 1630
(CO); δH (400 MHz; CDCl3) 5.1 (2H, s, CH2) 7.10 (1H, d, J 8.6,
ArH), 7.41–7.80 (4H, series of multiplets, ArH), 7.95 (1H, s,
4-H), 8.00 (1H, d, J 8.6, ArH) and 9.7 (1H, s, CHO); δC
(100 MHz; CDCl3) 63.2 (CH2), 114.0, 117.7, 121.0, 124.6,
128.1, 129.0, 129.4, 129.5, 131.1, 130.7, 134.2 and 137.6 (ArC
CH ), 3.32 (2H, m, CH ), 5.80 and 6.38 (2H, 2 × s, C᎐CH ) and
᎐
2
2
2
7.49–7.88 (10H, series of multiplets, ArH); δC (100 MHz;
CDCl3) 23.6 (CH2), 54.4 (CH2), 126.2, 128.1, 128.2, 129.4,
129.5, 133.9, 134.0, 137.8, 138.4 and 146.7 (ArC and C᎐CH ).
᎐
2
Diphenyl but-1-ene-2,4-disulfonate 9g
and C᎐CH) and 189.5 (CO); m/z 210 (Mϩ, 65.5%) and 181
᎐
A colourless oil (Found: Mϩ, 368.03881. C16H16O6S2 requires:
(100).
M, 368.03883); νmax (thin film/cmϪ1) 2922 (CH2) and 1588
(C᎐CH ); δ (400 MHz; CDCl3) 3.21 (2H, m, CH2), 3.63 (2H,
᎐
2
H
Phenyl 4-hydroxy-3,4-dihydro-2H-benzo[f]chromene-3-sulfonate
5r and phenyl 2H-benzo[f]chromene-3-sulfonate 6r
m, CH ), 6.01 and 6.02 (2H, 2 × s, C᎐CH ) and 7.18–7.43 (10H,
᎐
2
2
series of multiplets, ArH); δC (100 MHz; CDCl3) 25.8 (CH2),
48.6 (CH2), 121.8, 121.9, 127.5, 130.0, 130.1, 130.2, 130.3,
141.1, 148.9 and 149.1 (ArC and C᎐CH ).
2-Hydroxy-1-naphthaldehyde (0.5 g, 2.9 mmol) was reacted
with phenyl ethenesulfonate (0.80 g, 4.4 mmol) and DABCO
(0.26 g, 2.3 mmol) in CHCl3 (1.0 cm3) and water (1.0 cm3)
following the general procedure. Work-up and flash chrom-
atography gave two products:
᎐
2
Acknowledgements
The authors thank the National Research Foundation (NRF)
for a bursary (to X.W.N.) and both Rhodes University and the
NRF for generous financial support.
i) Phenyl 2H-benzo[f]chromene-3-sulfonate 6r. Yellow crys-
tals, mp 164–166 ЊC; νmax (chloroform/cmϪ1) 3022 (C᎐C–H) and
᎐
2923 (CH2); δH (400 MHz; CDCl3) 5.06 (2H, s, CH2), 7.10 (1H,
d, J 8.8, ArH), 7.21–7.80 (10H, series of multiplets, ArH) and
7.88 (1H, s, 4-H); δC (100 MHz; CDCl3) 63.2 (CH2), 113.2,
117.3, 121.3, 122.0, 122.3, 124.9, 127.4, 128.2, 128.8, 129.5,
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᎐
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