Diels-Alder reactions of 2′-hydroxychalcones with ortho-benzoquinodimethane: A new synthesis of 3-aryl-2-naphthyl 2-hydroxyphenyl ketones

Article abstract of DOI:10.1002/ejoc.200500872

Diels-Alder reactions of the 2′-hydroxychalcones 1a-e with oriho-benzoquinodimethane (3) yielded the 3-aryl-1,2,3,4-tetrahydro-2-naphthyl 2-hydroxyphenyl ketones 4a-e in good yields. The dehydrogenation of the cycloadducts 4a-e to 3-aryl-2-naphthyl 2-hydroxyphenyl ketones 5a-e was studied. Good results were obtained when DDQ was used as oxidant and microwave irradiation as energy source. Several benzoxanthone derivatives were also obtained as minor products. Structures of all new compounds were established by extensive NMR studies. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200500872

FULL PAPER
DOI: 10.1002/ejoc.200500872
Diels–Alder Reactions of 2Ј-Hydroxychalcones with ortho-Benzoquino-
dimethane: A New Synthesis of 3-Aryl-2-naphthyl 2-Hydroxyphenyl Ketones
Cristela M. Brito,[a] Diana C. G. A. Pinto,[a] Artur M. S. Silva,*[a] Ana M. G. Silva,[a]
Augusto C. Tomé,[a] and José A. S. Cavaleiro[a]
Keywords: 2-Naphthyl ketones / Benzophenones / Diels–Alder reactions / Microwave irradiation / Benzoxanthones
Diels–Alder reactions of the 2Ј-hydroxychalcones 1a–e with
ortho-benzoquinodimethane (3) yielded the 3-aryl-1,2,3,4-
tetrahydro-2-naphthyl 2-hydroxyphenyl ketones 4a–e in
good yields. The dehydrogenation of the cycloadducts 4a–e
to 3-aryl-2-naphthyl 2-hydroxyphenyl ketones 5a–e was
studied. Good results were obtained when DDQ was used as
oxidant and microwave irradiation as energy source. Several
benzoxanthone derivatives were also obtained as minor
products. Structures of all new compounds were established
by extensive NMR studies.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
asthma, diabetes, central nervous system dysfunction and
AIDS.[11,12]
Introduction
The benzophenone skeleton is a characteristic moiety of
a large number of natural and synthetic products that pres-
ent a wide-range of biological activities, including anti-in-
flammatory,[1] antitumour,[2,3] fungicidal,[4] anti-malarial[5]
and antimitotic[3] activity. Certain derivatives have also been
introduced as UV adsorbents for sunscreen purposes,[6]
whereas others exhibit moderate inhibitory activity of far-
nesyltransferase.[7] In fact inhibition of this enzyme has be-
come a major strategy for development of novel potential
anticancer drugs.
Some studies indicate that certain medicinal properties
of plants could result from the activity of both 2-hydroxy-
benzophenones and xanthones;[8] the former are the bio-
genic precursors of the latter.[9] It seems, from a structural
point of view, that 2-hydroxybenzophenones have the struc-
tural requirement for interaction with ATP-binding sites.
Thus, they also can be regarded as potential P-glycoprotein
modulators,[10] the gene responsible for the active transport
of chemotherapeutic drugs out of the cells. In addition, bal-
anol (I) (Figure 1), having a 2-hydroxybenzophenone moi-
ety, was isolated from the fungus Verticillium balanoides and
Fusarium merismoides.[11] The total synthesis of this natural
compounds[12] and of several analogues, maintaining the
benzophenone moiety, has attracted the interest of the sci-
entific community.[13] This interest is mainly due to the high
inhibitory activity of the fungal metabolite against protein
kinase C, a class of isoenzymes associated with a variety
of disorders, which include cancer, cardiovascular disorders,
Figure 1. Structure of biologicaly active compounds having 2-hy-
droxybenzophenone or naphthalene moieties.
The naphthalene skeleton is also present in a large
number of clinically used drugs, such as naphazoline (II), (a
cardiovascular agent),[13,14] nabumetone (III) and naproxen
(IV), anti-inflammatory agents with analgesic and antipy-
retic properties[13,15] (Figure 1). Recently, important phar-
macological properties, such as potential vasorelaxant[16]
and antitumour activities[13] were reported for compounds
bearing naphthalene moieties.
In the last five years, we have been interested in the reac-
tivity of several chromones as dienophiles in Diels–Alder
reactions with very reactive dienes.[17,18] As an extension of
these studies, and taking into consideration the potential
applications of compounds bearing 2-hydroxybenzophe-
[a] Department of Chemistry, University of Aveiro,
3810-193 Aveiro, Portugal
Fax: +351-234-370084
E-mail: arturs@dq.ua.pt
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Diels–Alder Reactions of 2Ј-Hydroxychalcones with o-Benzoquinodimethane
FULL PAPER
none and naphthalene moieties, we decided to study the 2-hydroxyphenyl ketones 4a–e, were obtained in good yields
Diels–Alder reactions of 2Ј-hydroxychalcones with the (Ͼ70%). The B ring substituents do not significantly affect
highly reactive diene ortho-benzoquinodimethane. The oxi- the yields of cycloaddition reactions.
dation of the resulting cycloadducts was also studied. This
synthetic strategy constitutes a new route for the synthesis pounds, the 3-aryl-2-naphthyl 2-hydroxyphenyl ketones 5a–
of some new functionalised 2-hydroxybenzophenones. e, the cycloadducts 4a–e were submitted to oxidation pro-
In order to achieve the synthesis of our target com-
Microwave-accelerated synthesis has attracted a substan- cedures. In the first attempt, the cycloadducts 4a–e were
tial amount of attention in recent years, and, as a conse- subjected to bromination with NBS, in the presence of ben-
quence, a great number of reports have been published in zoyl peroxide, and the products were then dehydrobromi-
the last decade advocating the advantages of using micro- nated by treatment with triethylamine. This method has
wave irradiation to carry out organic synthesis.[19] Signifi- been successfully applied in the dehydrogenation of other
cant increases in rates, yields and purities of products have tetrahydronaphthyl derivatives.[17] However, in the present
frequently been observed employing this non-conventional case, the desired products 5a–e were only obtained in poor
and energy-efficient heating method.[19] Typically, the oxi- yields (Ϸ 10%). In the second attempt we performed the
dation of the cycloadducts obtained from the Diels–Alder oxidation of cycloadducts 4b,d using the oxidising agent
reactions of 2Ј-hydroxychalcones with ortho-benzoquinodi- system DMSO/I2, which was already used in the oxidation
methane requires refluxing at high temperatures and/or of tetrahydroxanthone-type compounds.[18] In this case, the
with long reactions times. Therefore, we decided to explore TLC of the reaction mixture revealed the presence of se-
whether microwave irradiation could be used to enhance the veral products. The major fractions were isolated by prepar-
efficiency of this type of reaction. We report here a simple ative TLC and analysed by NMR spectroscopy. The NMR
and general procedure for the synthesis of 3-aryl-2-naphthyl spectra of the major products, which were obtained in mod-
2-hydroxyphenyl ketones 5a–e from the oxidation of cy- erate yields (Ϸ 30%), show a dihydroxanthone 6b,d[21] pro-
cloadducts 4a–e using microwave irradiation as energy file (Scheme 2). The expected products 5b,d were obtained
source.
in poor yields (Ͻ10%) and the NMR spectra of other
minor products indicate the presence of iodinated dihy-
droxanthones 7d1–d3 (R = Cl).[22] These results indicate
that the oxidation of cycloadducts 4b,d with a DMSO/I2
mixture led to the formation of the chromone nucleus fol-
lowed by the iodination of the most activated aromatic po-
Results and Discussion
Syntheses
Our study started with the Diels–Alder reaction of the sitions.[23] However, the complete aromatisation of these
appropriate 2Ј-hydroxychalcones 1a–e with ortho-benzoqui- compounds was not obtained under these experimental
nodimethane (3), formed in situ by thermal extrusion of conditions.
sulfur dioxide from 1,3-dihydrobenzo[c]thiophene 2,2-diox-
Because
2,3-dichloro-5,6-dicyano-1,4-benzoquinone
ide (2)[20] (Scheme 1). Because the double bond of chalcones (DDQ) is known as a powerful oxidant, particularly useful
is conjugated with the carbonyl group, these compounds for dehydrogenation to form aromatic compounds,[24] the
are expected to be good dienophiles. In fact their cycload- next attempt consisted in the treatment of cycloadducts 4a–
dition reactions with ortho-benzoquinodimethane can be e with an excess of DDQ, in refluxing 1,4-dioxane. How-
accomplished in refluxing 1,2,4-trichlorobenzene and the ever, when compounds 4a,b were treated in these condi-
expected cycloadducts, 3-aryl-1,2,3,4-tetrahydro-2-naphthyl tions, the target benzophenones 5a,b were obtained in poor
Scheme 1.
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A. M. S. Silva et al.
FULL PAPER
Scheme 2.
yields (15–18%) and compounds 8a,b (7–21%) and 9a,d (7–
9%) were also isolated as by-products (Scheme 2). By using
dry 1,4-dioxane the desired products 5a–e were obtained in
moderate yields (33–34%) for the cycloadducts 4a,d and in
poor yields (15–23%) for the other cycloadducts 4b,c,e.
Nevertheless, this method proved to be the one that allowed
the synthesis of the desired 3-aryl-2-naphthyl 2-hy-
droxyphenyl ketones 5a–e. Chromatographic separation of
the reaction mixtures allowed the recovery of some starting
materials (7–15%) and the isolation of the compounds 8a–
d (except for R = NO2) as by-products (Scheme 2).
The dehydrogenation mechanism of cyclohexanes by
DDQ starts with a hydride transfer to DDQ and the conse-
quent carbocation formation. In the case of the cycload-
ducts 4a–e the carbocation must be localised in the more
stable benzylic carbon atoms C-1, C-3 or C-4.[25] A carbo-
cation at C-2 is unfavourable because it is adjacent to a
carbonyl group. However, our results seem to indicate the
formation of carbocation at C-4 in 10a,b, because we have
isolated the diketones 9a,d. The formation of the 1,2,3,4-
tetrahydro-2-naphthyl 2-hydroxyphenyl ketones 9a,d can be
explained by the addition of water to the intermediate 10a,d
followed by the oxidation of the resulting benzyl alcohol
(Scheme 3). It is important to mention that compounds
9a,d were not detected when dry 1,4-dioxane was used, indi-
cating that their formations requires the presence of water.
The carbocations 10a–d can also loose a proton to give
the 3-aryl-1,2-dihydro-2-naphthyl-2-hydroxyphenyl ketones
11a–d, which can then transfer a hydride followed by an
Scheme 3.
acylium cation to DDQ to give 2-phenylnaphthalenes 8a– ergy into reactions,[19] we decided to perform the oxidation
d and the corresponding esters 12a–d (Scheme 3).[26] Other of the cycloadducts 4a–e by microwave irradiation. We used
examples of C–O coupling in oxidation reactions with the conditions recently described by us in the oxidation of
DDQ have been described;[25] the failed attempts to isolate some hydroaromatic compounds with DDQ under micro-
the esters 12a–d could be due to their instability as it has wave irradiation.[28] The mixture of cycloadducts 4a–e with
been reported for similar compounds.[27]
DDQ in 1,2,4-trichlorobenzene was irradiated at 170 °C for
Because the obtained results were not totally satisfactory, 30 minutes. Under these conditions, the 3-aryl-2-naphthyl
and taking into account that microwave radiation can be 2-hydroxyphenyl ketones 5a–e were obtained in good yields
an alternative to conventional heating for introducing en- (55–66%) and in notably shorter reactions times (Table 1).
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Diels–Alder Reactions of 2Ј-Hydroxychalcones with o-Benzoquinodimethane
Table 1. Yields (%) obtained in the oxidation reactions of cycloadducts 4a–e.
FULL PAPER
Entry Reactant
Classical conditions[a]
Microwave[b]
5a–e
8a–d
5a–e
8a–e
9a,d
13a–e
14a–d
15b,c
16a–d
1
2
3
4
5
4a
4b
4c
4d
4e
33
23
23
34
15
11
21
19
12
–
66
65
60
61
55
5
5
4
5
7
5
–
–
9
–
7
8
5
3
1
4
4
1
–
–
2
17
–
–
5
7
3
4
–
13
[a] DDQ (5 mol relative to the amount of 4a–e), freshly distilled 1,4-dioxane, reflux, 48 h. [b] DDQ (5 mol relative to the amount of 4a–
e), 1,2,4-trichlorobenzene, microwave irradiation: 36 min.
Scheme 4.
Several changes in temperatures and in reaction time al- 15b,c and 6-arylbenzo[a]xanthones 16a–d) as minor prod-
lowed the establishment of the best conditions for the syn- ucts (Table 1, Scheme 4). In two cases, the compounds 9a,d
thesis of 3-aryl-2-naphthyl 2-hydroxyphenyl ketones 5a–e (5–9%) were obtained as by-products, which could be due
and also for the isolation of 2-phenylnaphthalenes 8a–e and to the use of less dried cycloadducts 4a,b. In order to con-
several benzoxanthones (1-arylbenzo[c]xanthones 13a–e, firm this fact, the oxidation of cycloadduct 4a was per-
2-arylbenzo[c]xanthones 14a–d, 6-arylbenzo[b]xanthones formed by adding 0.1 mL of water to the reaction mixture.
Scheme 5.
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A. M. S. Silva et al.
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Under these conditions the yield of compound 9a was 4b–e were determined with the aid of HSQC and HMBC
doubled (12%). spectra. Figure 2 (A) shows the most important connectivi-
The improved yields of 3-aryl-2-naphthyl 2-hydroxy- ties found in the HMBC spectra of these compounds.
phenyl ketones 5a–e were expected, along with the forma-
tion of by-products. The unexpected results were the four
types of benzoxanthones obtained as by-products. The for-
mation of 1-arylbenzo[c]xanthones 13a–e can be explained
by the fact, also detected with other oxidizing agents, that
cycloadducts 4a–e in DDQ could generate the chromone
moieties 6a–e, which could be oxidised to the corresponding
xanthones 13a–e (Scheme 5). The formation of the other
by-products can be explained by the formation of benzylic
cations 10a–d and 17a–e, due to the reaction of 4a–e with
DDQ, followed by an 1,2-aryl or benzoyl shift, giving the
intermediates 18a–d and 20a–d which afforded the obtained
xanthones 14a–d, 15b,c and 16a–d after cyclodehydrogena-
tion as depicted in Scheme 5. A similar type of intermediate
and rearrangement was postulated to explain the pyrone
derivatives from lignans.[29] The strong deactivating effect
of the nitro group can explain why these by-products were
not detected in the oxidation of 2-hydroxyphenyl 3-(4-ni-
trophenyl)-2-naphthyl ketone (4e).
Figure 2. Important connectivities found in the HMBC spectra of
compounds 4a–e, 5a–e and 9a,b,d.
Nuclear Magnetic Resonance Spectroscopy
1
1
The H NMR spectra of the cycloadducts 4a–e present
The H NMR spectra of compounds 5a–e also present
signals in the aromatic and aliphatic regions, besides the the signal corresponding to the resonance of the hydroxylic
signal at δ = 12.17–12.36 ppm, which is due to the reso- proton (2Ј-OH) (δ = 11.88–12.08 ppm, as a singlet). In the
nance of hydroxylic proton (2Ј-OH) involved in an intramo- aromatic region of these spectra, one can also observe the
lecular hydrogen bond with the carbonyl group. The reso- common structural features of the rings A and B of com-
nances appearing in the aliphatic region are due to protons pounds 4a–e. However the resonances which immediately
1-H, 2-H, 3-H and 4-H. In terms of stereochemistry of indicate the oxidation of cycloadducts 4a–e are those of 1-
these compounds, the most important resonances are those H and 4-H, which appear as singlets at δ = 7.94–8.04 and
of 2-H and 3-H, which appear, in most cases, as double 7.92–7.98 ppm, respectively. The resonances of all carbon
doublet of doublets at δ = 4.14–4.23 and 3.48–3.68 ppm, atoms of 2-hydroxybenzophenones 5a–e were determined
respectively. The coupling constants 3J2-H,3-H Ϸ 11 Hz indi- with the aid of HSQC and HMBC experiments. The most
cate a trans configuration of these two protons, which is important connectivities found in the HMBC spectra al-
consistent with the stereospecificity of the Diels–Alder reac- lowed the unequivocal assignment of the quaternary carbon
tion (the starting 2Ј-hydroxychalcones 1a–e have trans con- resonances and the confirmation of those corresponding to
figuration).
1-H and 4-H (Figure 2, B).
The main characteristics of the 1H NMR spectra of com-
1
In the aromatic region of the H NMR spectra of 4a–e,
one can detect the common structural feature of the ring pounds 8a–e are the resonances of the 1-H (d, δ Ϸ
A, which appears in each case as ABCD spin systems corre- 7.9 ppm), 3-H (dd, δ Ϸ 7.7 ppm) and 4-H (br. s, δ Ϸ
sponding to 3Ј-H, 4Ј-H, 5Ј-H and 6Ј-H proton resonances. 8.0 ppm) protons. Another important spectroscopic aspect
6Ј-H and 3Ј-H resonances appear in most cases as double of the 13C NMR spectroscopic data of these compounds is
doublets whereas those of 4Ј-H and 5Ј-H appear as double the absence of the characteristic carbon resonance due to
doublet of doublets. The resonances of 4Ј-H and 6Ј-H ap- the carbonyl group. The assignment of the protonated car-
pear at higher frequencies (δ = 7.41–7.47 and 7.78– bon resonances of compounds 8a–e was based on the analy-
7.84 ppm, respectively) than those corresponding to 3Ј-H sis of their HSQC spectra, whereas those of the quaternary
and 5Ј-H (δ = 6.89–6.93 and 6.84–6.90 ppm, respectively). carbon atoms were based on the connectivities found in
This is due to the mesomeric and anisotropic deshielding their HMBC spectra.
effect of the carbonyl group in 6Ј-H and resonance effect
The 1H NMR spectra of 3-aryl-4-oxo-1,2,3,4-tetrahydro-
on 4Ј-H. Another important feature is the presence of an 2-naphthyl 2-hydroxyphenyl ketones 9a,d indicate a partial
AB spin system characteristic of the para-substituted B ring oxidation of the corresponding cycloadducts 4a,d, because
in cycloadducts 4b–e.
the resonances corresponding to only four protons were ob-
The resonances of all other protons and the unequivocal served in the aliphatic region of these spectra. However, un-
assignment of the carbon resonances of the cycloadducts equivocal supports for this structure are the presence of two
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Diels–Alder Reactions of 2Ј-Hydroxychalcones with o-Benzoquinodimethane
FULL PAPER
carbonyl carbon resonances at δ Ϸ 197 and ca. 205 ppm in which presents a chemical shift characteristic of a proton
their 13C NMR spectra. These data and the analysis of their near a carbonyl group[27] and deshielded by its anisotropic
HMBC spectra (Figure 2, C) provide unequivocal support and mesomeric effects. The signal is consequently attributed
for the proposed structures.
to the resonance of proton 1-H. These data and the analysis
1
An important characteristic of the H NMR spectra of of their HMBC spectra (Figure 3, B) provide unequivocal
1-arylbenzo[c]xanthones 13a–e is the absence of the singlet support for the proposed structures. The most noticeable
peak due to the 2Ј-OH group. The proton resonances of feature in the characterization of the 6-arylbenzo[b]xan-
H-2 appear as singlets at δ Ϸ 7.5 ppm and indicate the pres- thones 15b,c is the singlet at δ Ϸ 9.0 ppm due to the proton
ence of a fully aromatic C ring. Other relevant features of H-1 resonance.[18,31] These xanthones present several signals
1
the H NMR spectra of 13a–e are the characteristic A and both in 1H and 13C NMR spectra, which are similar to
D ring resonances: i) 11-H ( δ Ϸ 8.3 ppm) and 9-H (Ϸ δ = those of the other xanthones. Their differentiation and si-
7.7 ppm) appeared at higher frequency values than those of multaneous unequivocal support for the proposed structure
8-H ( δ Ϸ 7.3 ppm) and 10-H ( δ Ϸ 7.3 ppm), because of were achieved by the connectivities found in HMBC spectra
both anisotropic and mesomeric deshielding effects of the (Figure 3, C). Finally, the features in the 6-arylbenzo[a]xan-
carbonyl group for 11-H and only the latter for 9-H; ii) 6- thones 16a–d characterization are: i) the singlet at δ Ϸ
H ( δ Ϸ 8.7 ppm) appeared at higher frequency values than 8.1 ppm corresponding to the resonance of proton H-5; ii)
those of protons 3-H ( δ Ϸ 7.9 ppm) because of the the doublet at δ Ϸ 10.1 ppm due to the resonance of proton
through-space deshielding effect of the heterocyclic oxygen H-1, which is the most deshielded proton as a consequence
atom.
of the anisotropic effect of the carbonyl group. The connec-
The 13C NMR spectra of compounds 13a–e confirm the tivities found in HMBC spectra (Figure 3, D) allowed the
xanthone-type structure, because typical carbonyl carbon confirmation for the resonance assignments of protonated
resonances (δ Ϸ 176–178 ppm) of xanthone-type com- carbon atoms and the unequivocal assignment of the qua-
pounds have been identified.[30] The assignment of the pro- ternary carbon atoms.
tonated carbon resonances of compounds 13a–e was based
on the analysis of their HSQC spectra, whereas those of the
quaternary carbon atoms were based on the connectivity
Experimental Section
found in their HMBC spectra (Figure 3, see part A, shown
General Remarks: Melting points were measured with a Reichert
as an example). The 1H NMR spectra of 2-arylbenzo[c]xan-
Thermovar apparatus fitted with a microscope and are uncor-
thones 14a–d confirm the presence of a fully aromatic nu-
cleus of benzo[c]xanthone like in 1-arylbenzo[c]xanthones
13a–e. The main difference is the singlet at δ Ϸ 8.2 ppm,
rected. NMR spectra were recorded with Bruker Avance 300 spec-
1
trometers (300.13 MHz for H and 75.47 MHz for 13C), in CDCl3
as solvent, if not stated otherwise. Chemical shifts (δ) are reported
in ppm and coupling constants (J) in Hz; internal standard was
TMS. Unequivocal 13C assignments were made with the aid of 2D
gHSQC and gHMBC (delays for one bond and long-range J C/H
couplings were optimised for 145 and 7 Hz, respectively) experi-
ments. Electron impact (EI = 70 eV) MS were recorded with VG
Autospec Q and M spectrometers. Elemental analyses were ob-
tained with a LECO 932 CHNS analyser. Reactions under micro-
wave irradiation were performed with an Ethos SYNTH microwave
labstation (Milestone) using glassware setup for atmospheric-pres-
sure reactions (temperature measurement with a fiber-optic probe).
Preparative thin-layer chromatography was performed with Merck
silica gel 60 DGF254. Column chromatography was performed with
Merck silica gel 60, 70–230 mesh. All chemicals and solvents used
were obtained from commercial sources and used as received or
dried using standard procedures.
2Ј-Hydroxychalcones 1a–e: Prepared by base-catalysed aldol con-
densation as previously reported.[32]
1,3-Dihydrobenzo[c]thiophene 2,2-Dioxide (2): Prepared according
to a literature procedure.[20]
General Procedure for the Synthesis of 3-Aryl-1,2,3,4-tetrahydro-2-
naphthyl 2-Hydroxyphenyl Ketones 4a–e: 1,3-Dihydrobenzo[c]thio-
phene 2,2-dioxide (2) (0.443 g, 2.64 mmol) was added to a solution
of the appropriate 2Ј-hydroxychalcone 1a–e (2.2 mmol) in 1,2,4-
trichlorobenzene (40 mL). The mixture was refluxed under nitrogen
for 18 h. After this period the reaction mixture was purified by
silica gel column chromatography eluting with light petroleum
ether to remove the 1,2,4-trichlorobenzene and with dichlorometh-
Figure 3. Important connectivities found in the HMBC spectra of
compounds 13a–e, 14a–d, 15b,c and 16a–d.
ane to collect the cycloadducts 4a–e.
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A. M. S. Silva et al.
2-Hydroxyphenyl 3-Phenyl-1,2,3,4-tetrahydro-2-naphthyl Ketone 132.1 (C-1ЈЈ), 134.1 and 135.3 (C-9 and C-10), 136.6 (C-4Ј), 142.3
FULL PAPER
(4a): Yield 70% (508 mg). M.p. 93–94 °C (recrystallisation from
ethanol). H NMR: δ = 3.04–3.22 (m, 4 H, 1,4-H), 3.52 (ddd, J =
(C-4ЈЈ), 162.9 (C-2Ј), 208.1 (C=O). EI-MS: m/z (%) = 362 (30)
[M+·], 344 (15), 237 (21), 226 (24), 219 (17), 121 (100), 104 (10), 84
(10), 65 (7). FAB-HRMS (C23H19O2Cl [M+H]+): calcd. 362.1076,
found 362.1074.
1
11.2, 10.6 and 5.7 Hz, 1 H, 3-H), 4.22 (ddd, J = 10.6, 9.2 and
7.4 Hz, 1 H, 2-H), 6.86 (ddd, J = 7.9, 7.7 and 1.1 Hz, 1 H, 5Ј-
H), 6.90 (dd, J = 8.2 and 1.1 Hz, 1 H, 3Ј-H), 7.09–7.18 (m, 5 H,
2ЈЈ,3ЈЈ,4ЈЈ,5ЈЈ,6ЈЈ-H), 7.20–7.24 (m, 4 H, 5,6,7,8-H), 7.42 (ddd, J =
8.2, 7.7 and 1.6 Hz, 1 H, 4Ј-H), 7.82 (dd, J = 7.9 and 1.6 Hz, 1 H,
6Ј-H), 12.35 (s, 1 H, 2Ј-OH). 13C NMR: δ = 34.8 (C-4), 37.9 (C-1),
42.7 (C-3), 46.4 (C-2), 118.6 (C-3Ј), 118.8 (C-5Ј), 119.1 (C-1Ј), 126.3
(C-4ЈЈ), 126.1 and 126.6 (C-6 and C-7), 127.1 (C-2ЈЈ,6ЈЈ), 128.4 and
128.6 (C-5 and C-8), 128.5 (C-3ЈЈ,5ЈЈ), 129.6 (C-6Ј), 134.4 and 135.7
(C-9 and C-10), 136.5 (C-4Ј), 143.8 (C-1ЈЈ), 162.9 (C-2Ј), 208.5
(C=O). EI-MS: m/z (%) = 328 (26) [M+·], 310 (20), 237 (15), 219
(13), 206 (6), 192 (30), 129 (9), 121 (100), 91 (30), 77 (7), 65 (17).
C23H20O2 (328.40): calcd. C 84.12, H 6.14; found C 83.99, H 5.96.
2-Hydroxyphenyl 3-(4-Nitrophenyl)-1,2,3,4-tetrahydro-2-naphthyl
Ketone (4e): Yield 80% (656 mg). M.p. 148–149 °C (recrystalli-
sation from ethanol). 1H NMR: δ = 3.03–3.28 (m, 4 H, 1,4-H),
3.68 (ddd, J = 11.3, 11.0 and 5.5 Hz, 1 H, 3-H), 4.23 (dt, J = 11.0
and 5.3 Hz, 1 H, 2-H), 6.90 (ddd, J = 8.1, 7.4 and 1.1 Hz, 1 H, 5Ј-
H), 6.93 (dd, J = 8.1 and 1.1 Hz, 1 H, 3Ј-H), 7.14–7.22 (m, 4 H,
5,6,7,8-H), 7.40 (d, J = 8.8 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.47 (ddd, J = 8.1,
7.4 and 1.6 Hz, 1 H, 4Ј-H), 7.82 (dd, J = 8.1 and 1.6 Hz, 1 H, 6Ј-
H), 8.09 (d, J = 8.8 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 12.17 (s, 1 H, 2Ј-OH). 13C
NMR: δ = 34.9 (C-4), 37.5 (C-1), 42.6 (C-3), 46.5 (C-2), 118.7
(C-1Ј), 118.9 (C-3Ј), 119.1 (C-5Ј), 123.9 (C-3ЈЈ,5ЈЈ), 126.5 and 126.6
(C-6 and C-7), 128.1 (C-2ЈЈ,6ЈЈ), 128.5 and 128.6 (C-5 and C-8),
129.4 (C-6Ј), 133.9 and 134.7 (C-9 and C-10), 137.0 (C-4Ј), 146.6
(C-1ЈЈ), 151.7 (C-4ЈЈ), 163.1 (C-2Ј), 207.5 (C=O). EI-MS: m/z (%)
= 373 (29) [M+·], 356 (22), 235 (29), 147 (5), 128 (6), 121 (100), 93
(10), 65 (11). C23H19O4N (373.40): calcd. C 73.98, H 5.13, N 3.75;
found C 73.63, H 4.79, N 4.03.
2-Hydroxyphenyl 3-(4-Methylphenyl)-1,2,3,4-tetrahydro-2-naphthyl
Ketone (4b): Yield 95% (714 mg). M.p. 103–105 °C (recrystalli-
1
sation from ethanol). H NMR: δ = 2.25 (s, 3 H, 4ЈЈ-CH3), 3.01–
3.21 (m, 4 H, 1,4-H), 3.50 (ddd, J = 11.2, 10.5 and 5.6 Hz, 1 H, 3-
H), 4.21 (dt, J = 10.5 and 6.8 Hz, 1 H, 2-H), 6.87 (ddd, J = 8.3,
7.3 and 1.1 Hz, 1 H, 5Ј-H), 6.91 (dd, J = 8.1 and 1.1 Hz, 1 H, 3Ј-
H), 7.02 (d, J = 8.1 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 7.11 (d, J = 8.1 Hz, 2 H,
2ЈЈ,6ЈЈ-H), 7.13–7.20 (m, 4 H, 5,6,7,8-H), 7.44 (ddd, J = 8.1, 7.3
and 1.5 Hz, 1 H, 4Ј-H), 7.84 (dd, J = 8.3 and 1.5 Hz, 1 H, 6Ј-H),
12.35 (s, 1 H, 2Ј-OH). 13C NMR: δ = 21.0 (4ЈЈ-CH3), 34.9 (C-4),
38.2 (C-1), 42.2 (C-3), 46.4 (C-2), 118.6 (C-3Ј), 118.9 (C-5Ј), 119.1
(C-1Ј), 126.1 and 126.3 (C-6 and C-7), 127.0 (C-2ЈЈ,6ЈЈ), 128.4 and
128.7 (C-5 and C-8), 129.3 (C-3ЈЈ,5ЈЈ), 129.7 (C-6Ј), 134.5 and 135.9
(C-9 and C-10), 136.1 (C-4ЈЈ), 136.5 (C-4Ј), 140.8 (C-1ЈЈ), 163.0
(C-2Ј), 208.6 (C=O). EI-MS: m/z (%) = 342 (30) [M+·], 324 (10),
237 (173), 219 (13), 206 (23), 129 (8), 121 (100), 105 (28), 91 (6),
77 (5), 65 (14). C24H22O2 (342.43): calcd. C 84.18, H 6.48; found
C 84.34, H 6.66.
General Procedure for the Synthesis of 3-Aryl-2-naphthyl 2-hy-
droxyphenyl Ketones 5a-e under Classical Heating Conditions.
Method A: DDQ (0.292 g, 1.3 mmol) was added to a solution
of the appropriate 3-aryl-1,2,3,4-tetrahydro-2-naphthyl 2-hy-
droxyphenyl ketone 4a,b (0.259 mmol) in 1,4-dioxane (10 mL). The
reaction mixture was refluxed under nitrogen for 48 hours. After
this period the reaction mixture was washed with water and puri-
fied by preparative TLC eluting with a 1:1 mixture of dichloro-
methane/light petroleum ether, leading to the isolation of three
main spots, in each case. The spot of higher Rf value was identified
as being 2-phenylnaphthalenes 8a,b (8a, 7%; 8b, 21%), the middle
Rf value spot was identified as being (3-aryl-2-naphthyl) (2-hy-
droxyphenyl) ketones 5a,b (5a, 15%, 5b, 18%), the compounds with
lower Rf values were identified as ketones 9a,b (9a, 7%; 9b, 9%).
2-Hydroxyphenyl 3-(4-Methoxyphenyl)-1,2,3,4-tetrahydro-2-naph-
thyl Ketone (4c): Yield 87% (687 mg). M.p. 100–103 °C (recrystalli-
sation from ethanol). 1H NMR: δ = 3.08–3.20 (m, 4 H, 1,4-H),
3.48 (ddd, J = 11.1, 10.7 and 5.7 Hz, 1 H, 3-H), 3.72 (s, 3 H, 4ЈЈ-
OCH3), 4.16 (dt, J = 10.7 and 8.3 Hz, 1 H, 2-H), 6.75 (d, J =
8.4 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 6.86 (ddd, J = 8.1, 7.9 and 0.8 Hz, 1 H, 5Ј-
H), 6.91 (d, J = 8.1 Hz, 1 H, 3Ј-H), 7.11–7.20 (m, 4 H, 5,6,7,8-H),
7.14 (d, J = 8.4 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.43 (ddd, J = 8.1, 7.9 and
1.1 Hz, 1 H, 4Ј-H), 7.81 (dd, J = 8.1 and 1.1 Hz, 1 H, 6Ј-H), 12.36
(s, 1 H, 2Ј-OH). 13C NMR: δ = 34.8 (C-4), 38.0 (C-1), 42.0 (C-3),
46.7 (C-2), 55.1 (4ЈЈ-OCH3), 114.0 (C-3ЈЈ,5ЈЈ), 118.6 (C-3Ј), 118.9
(C-5Ј), 119.2 (C-1Ј), 126.1 and 126.3 (C-6 and C-7), 128.1
(C-2ЈЈ,6ЈЈ), 128.4 and 128.7 (C-5 and C-8), 129.7 (C-6Ј), 134.5 and
135.8 (C-9 and C-10), 135.8 (C-1ЈЈ), 136.5 (C-4Ј), 158.1 (C-4ЈЈ),
163.0 (C-2Ј), 208.7 (C=O). EI-MS: m/z (%) = 358 (12) [M+·], 340
(3), 237 (3), 222 (10), 129 (5), 121 (100), 104 (6), 77 (4), 65 (8).
C24H22O3 (358.43): calcd. C 80.42, H 6.19; found C 80.20, H 6.09.
Method B: The procedure was identical to that described for
method A except that freshly dried 1,4-dioxane was used as solvent.
Purification of the reaction mixture by preparative TLC afforded
compounds 8a–d and 5a–e (yields indicated in Table 1). Some un-
changed starting material was also recovered: 4a, 8%; 4b, 11%; 4c,
12%; 4d, 7%; 4e, 15%.
2-Hydroxyphenyl 3-Phenyl-2-naphthyl Ketone (5a): Yellow oil. 1H
NMR: δ = 6.70 (dt, J = 7.6 and 1.0 Hz, 1 H, 5Ј-H), 6.96 (d, J =
8.1 Hz, 1 H, 3Ј-H), 7.22–7.30 (m, 3 H, 3ЈЈ,4ЈЈ,5ЈЈ-H), 7.33–7.42 (m,
4 H, 4Ј,6Ј-H and 2ЈЈ,6ЈЈ-H), 7.54–7.65 (m, 2 H, 6,7-H), 7.90–7.97
(m, 2 H, 5,8-H), 7.96 (s, 1 H, 1-H), 7.97 (s, 1 H, 4-H), 12.03 (s, 1
H, 2Ј-OH). 13C NMR: δ = 118.0 (C-3Ј), 118.7 (C-5Ј), 120.2 (C-1Ј),
127.4 (C-4ЈЈ), 127.0 and 128.0 (C-6 and C-7), 128.0 (C-5), 128.3
(C-8), 128.5 (C-3ЈЈ,5ЈЈ), 128.85 (C-2ЈЈ,6ЈЈ), 128.89 (C-1), 129.4
(C-4), 131.3 (C-2), 133.6 (C-6Ј), 134.0 (C-10), 135.9 (C-9) 136.5
(C-4Ј), 138.0 (C-3), 140.0 (C-1ЈЈ), 162.9 (C-2Ј), 203.6 (C=O). EI-
MS: m/z (%) = 324 (100) [M+·], 323 (63), 305 (28), 276 (6), 247 (37),
231 (23), 204 (56), 202 (43), 153 (10), 121 (39), 93 (12), 65 (15).
FAB-HRMS (C23H16O2 [M+H]+): calcd. 324.1150, found
324.1141.
3-(4-Chlorophenyl)-1,2,3,4-tetrahydro-2-naphthyl 2-Hydroxyphenyl
1
Ketone (4d): Yield 75% (599 mg). Yellow oil. H NMR: δ = 2.97–
3.17 (m, 4 H, 1,4-H), 3.49 (ddd, J = 11.3, 10.7 and 5.6 Hz, 1 H, 3-
H), 4.14 (ddd, J = 10.7, 10.4 and 6.2 Hz, 1 H, 2-H), 6.84 (ddd, J
= 7.9, 7.7 and 1.1 Hz, 1 H, 5Ј-H), 6.89 (dd, J = 8.1 and 1.1 Hz, 1
H, 3Ј-H), 7.07–7.21 (m, 8 H, 5,6,7,8-H and 2ЈЈ,3ЈЈ,5ЈЈ,6ЈЈ-H), 7.41 2-Hydroxyphenyl 3-(4-Methylphenyl)-2-naphthyl Ketone (5b): M.p.
1
(ddd, J = 8.1, 7.7 and 1.6 Hz, 1 H, 4Ј-H), 7.78 (dd, J = 7.9 and
133–135 °C (recrystallisation from ethanol). H NMR: δ = 2.31 (s,
1.6 Hz, 1 H, 6Ј-H), 12.31 (s, 1 H, 2Ј-OH). 13C NMR: δ = 34.7 3 H, 4ЈЈ-CH3), 6.77 (ddd, J = 8.4, 7.4 and 1.1 Hz, 1 H, 5Ј-H), 6.98
(C-4), 37.7 (C-1), 42.0 (C-3), 46.4 (C-2), 118.7 (C-3Ј), 118.91 (C-5Ј), (dd, J = 8.5 and 1.1 Hz, 1 H, 3Ј-H), 7.11 (d, J = 8.2 Hz, 2 H,
118.89 (C-1Ј), 126.2 and 126.4 (C-6 and C-7), 128.51 (C-2ЈЈ,6ЈЈ),
128.2 and 128.57 (C-5 and C-8), 128.6 (C-3ЈЈ,5ЈЈ), 129.5 (C-6Ј),
3ЈЈ,5ЈЈ-H), 7.28 (d, J = 8.2 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.40 (d, J = 8.4 Hz,
1 H, 6Ј-H), 7.42 (dd, J = 8.5 and 7.4 Hz, 1 H, 4Ј-H), 7.53–7.64 (m,
2564
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 2558–2569

Diels–Alder Reactions of 2Ј-Hydroxychalcones with o-Benzoquinodimethane
FULL PAPER
2 H, 6,7-H), 7.89–7.94 (m, 2 H, 5,8-H), 7.92 (s, 1 H, 1-H), 7.94 (s, J = 8.5 Hz, 1 H, 4-H), 8.05 (d, J = 1.6 Hz, 1 H, 1-H). 13C NMR:
1 H, 4-H), 12.05 (s, 1 H, 2Ј-OH). 13C NMR: δ = 21.1 (4ЈЈ-CH3), δ = 125.6 (C-3), 125.8 (C-1), 125.9 and 126.3 (C-6 and C-7), 127.3
118.1 (C-3Ј), 118.7 (C-5Ј), 120.2 (C-1Ј), 126.9 and 127.89 (C-6 and
(C-4Ј), 127.4 (C-2Ј,6Ј), 127.6 (C-5), 128.2 (C-8), 128.4 (C-4), 128.8
C-7), 127.93 (C-5), 128.8 (C-8), 128.3 (C-1), 128.7 (C-2ЈЈ,6ЈЈ), 129.3 (C-3Ј,5Ј), 132.6 (C-10) 133.6 (C-9), 138.5 (C-3), 141.1 (C-1Ј). EI-
(C-4 and C-3ЈЈ,5ЈЈ), 131.2 (C-2), 133.7 (C-6Ј), 134.0 (C-10), 135.9 MS: m/z (%) = 204 (100) [M+·], 203 (22), 202 (36), 176 (6), 101 (14),
(C-9), 136.5 (C-4Ј), 137.1 (C-1ЈЈ), 137.2 (C-3), 138.0 (C-4ЈЈ), 162.9
89 (8), 76 (5). FAB-HRMS (C16H12 [M+H]+): calcd. 204.0939,
(C-2Ј), 203.7 (C=O). EI-MS: m/z (%) = 338 (100) [M+·], 337 (59), found 204.0934.
319 (19), 305 (19), 247 (32), 245 (18), 218 (45), 215 (20), 202 (34),
169 (10), 121 (28), 93 (10), 65 (12). C24H18O2 (338.40): calcd. C
85.18, H 5.36; found C 84.97, H 5.28.
2-(4-Methylphenyl)naphthalene (8b): M.p. 75–78 °C (recrystalli-
sation from ethanol). H NMR: δ = 2.43 (s, 3 H, 4Ј-CH3), 7.30 (d,
1
J = 8.1 Hz, 2 H, 3Ј,5Ј-H), 7.44–7.52 (m, 2 H, 6,7-H), 7.63 (d, J =
8.1 Hz, 2 H, 2Ј,6Ј-H), 7.74 (dd, J = 8.6 and 1.6 Hz, 1 H, 3-H),
7.84–7.90 (m, 2 H, 5,8-H), 7.90 (d, J = 8.6 Hz, 1 H, 4-H), 8.02 (br.
s, 1 H, 1-H). 13C NMR: δ = 21.1 (4Ј-CH3), 125.4 (C-1), 125.5 (C-3),
125.8 and 126.2 (C-6 and C-7), 127.2 (C-2Ј,6Ј), 127.6 (C-5), 128.1
(C-8), 128.3 (C-4), 129.6 (C-3Ј,5Ј), 132.5 (C-10) 133.7 (C-9), 137.2
(C-4Ј), 138.2 (C-1Ј), 138.5 (C-2). EI-MS: m/z (%) = 218 (100) [M+·],
217 (25), 215 (23), 202 (26), 189 (8), 109 (10), 101 (5), 65 (2). FAB-
HRMS (C17H14 [M+H]+): calcd. 218.1096, found 218.1104.
2-Hydroxyphenyl 3-(4-Methoxyphenyl)-2-naphthyl Ketone (5c): Yel-
1
low oil. H NMR: δ = 3.77 (s, 3 H, 4ЈЈ-OCH3), 6.70 (ddd, J = 8.2,
7.5 and 0.8 Hz, 1 H, 5Ј-H), 6.84 (d, J = 8.7 Hz, 2 H, 3ЈЈ,5ЈЈ-H),
6.97 (dd, J = 8.1 and 0.8 Hz, 1 H, 3Ј-H), 7.31 (d, J = 8.7 Hz, 2 H,
2ЈЈ,6ЈЈ-H), 7.35 (dd, J = 8.2 and 1.6 Hz, 1 H, 6Ј-H), 7.40 (ddd, J =
8.1, 7.5 and 1.6 Hz, 1 H, 4Ј-H), 7.52–7.63 (m, 2 H, 6,7-H), 7.92 (s,
1 H, 1-H), 7.94 (s, 1 H, 4-H), 7.89–7.94 (m, 2 H, 5,8-H), 12.08 (s,
1 H, 2Ј-OH). 13C NMR: δ = 55.2 (4ЈЈ-OCH3), 114.0 (C-3ЈЈ,5ЈЈ),
118.1 (C-3Ј), 118.7 (C-5Ј), 120.1 (C-1Ј), 126.8 and 127.9 (C-6 and
C-7), 127.9 (C-5), 128.3 (C-8), 128.7 (C-1), 129.0 (C-4), 130.0
(C-2ЈЈ,6ЈЈ), 131.1 (C-2), 132.4 (C-1ЈЈ), 133.6 (C-6Ј), 134.0 (C-10),
136.0 (C-9) 136.5 (C-4Ј), 137.5 (C-3), 159.0 (C-4ЈЈ), 162.9 (C-2Ј),
203.9 (C=O). EI-MS: m/z (%) = 354 (100) [M+·] 353 (41), 335 (7),
305 (13), 261 (15), 247 (20), 234 (29), 218 (11), 202 (11), 189 (22),
177 (11), 121 (30), 93 (9), 65 (11). FAB-HRMS (C24H18O3 [M +
H]+): calcd. 354.1256, found 354.1248.
2-(4-Methoxyphenyl)naphthalene (8c): M.p. 135–137 °C (recrystalli-
1
sation from ethanol). H NMR: δ = 3.87 (s, 3 H, 4Ј-OCH3), 7.02
(d, J = 8.8 Hz, 2 H, 3Ј,5Ј-H), 7.43–7.52 (m, 2 H, 6,7-H), 7.66 (d, J
= 8.8 Hz, 2 H, 2Ј,6Ј-H), 7.72 (dd, J = 8.5 and 1.8 Hz, 1 H, 3-H),
7.83–7.89 (m, 2 H, 5,8-H), 7.89 (d, J = 8.5 Hz, 1 H, 4-H), 7.99 (br.
s, 1 H, 1-H). 13C NMR: δ = 55.4 (4Ј-OCH3), 114.3 (C-3Ј,5Ј), 125.0
(C-1), 125.4 (C-3), 125.6 and 126.2 (C-6 and C-7), 127.6 (C-5),
128.0 (C-8), 128.3 (C-4), 128.4 (C-2Ј,6Ј), 132.3 (C-10) 133.6 (C-1Ј),
133.7 (C-9), 138.1 (C-2),159.2 (C-4Ј). EI-MS: m/z (%) = 234 (100)
[M+·], 219 (39), 202 (7), 191 (25), 189 (23), 165 (13), 117 (13), 83
(5). C17H14O (234.29): calcd. C 87.15, H 6.02; found C 87.61, H
5.84.
3-(4-Chlorophenyl)-2-naphthyl 2-Hydroxyphenyl Ketone (5d): M.p.
98–101 °C (recrystallisation from ethanol). 1H NMR: δ = 6.73
(ddd, J = 8.2, 7.1 and 0.9 Hz, 1 H, 5Ј-H), 6.99 (d, J = 8.1 Hz, 1 H,
3Ј-H), 7.11 (d, J = 8.2 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 7.28 (d, J = 8.2 Hz, 2
H, 2ЈЈ,6ЈЈ-H), 7.36 (dd, J = 8.2 and 1.6 Hz, 1 H, 6Ј-H), 7.43 (ddd,
J = 8.1, 7.1 and 1.6 Hz, 1 H, 4Ј-H), 7.58–7.64 (m, 2 H, 6,7-H),
7.91–7.96 (m, 2 H, 5,8-H), 7.92 (s, 1 H, 1-H), 7.97 (s, 1 H, 4-H),
11.99 (s, 1 H, 2Ј-OH). 13C NMR: δ = 118.3 (C-3Ј), 118.8 (C-5Ј),
120.1 (C-1Ј), 127.2 and 128.0 (C-6 and C-7), 128.1 (C-5), 128.4
(C-1), 128.7 (C-2ЈЈ,6ЈЈ), 129.1 (C-8), 129.4 (C-4), 130.1 (C-3ЈЈ,5ЈЈ),
131.4 (C-2), 133.5 (C-6Ј), 133.6 (C-1ЈЈ), 133.9 (C-10), 135.6 (C-9)
136.7 (C-4Ј), 136.9 (C-3), 138.5 (C-4ЈЈ), 163.0 (C-2Ј), 203.3 (C=O).
EI-MS: m/z (%) = 358 (100) [M+·], 357 (60), 341 (17), 305 (17), 265
(23), 247 (45), 238 (63), 230 (15), 202 (56), 179 (7), 162 (14), 153
(7), 138 (8), 121 (53), 93 (17), 65 (22). C23H15O2Cl (358.82): calcd.
C 76.99, H 4.21; found C 76.59, H 4.11.
2-(4-Chlorophenyl)naphthalene (8d): M.p. 133–134 °C (recrystalli-
sation from ethanol). 1H NMR: δ = 7.46 (d, J = 8.5 Hz, 2 H, 3Ј,5Ј-
H), 7.50–7.55 (m, 2 H, 6,7-H), 7.65 (d, J = 8.5 Hz, 2 H, 2Ј,6Ј-H),
7.70 (dd, J = 8.6 and 1.8 Hz, 1 H, 3-H), 7.86–7.91 (m, 2 H, 5,8-
H), 7.92 (d, J = 8.6 Hz, 1 H, 4-H), 8.01 (br. s, 1 H, 1-H). 13C NMR:
δ = 125.2 (C-3), 125.7 (C-1), 126.1 and 126.4 (C-6 and C-7), 127.6
(C-5), 128.2 (C-8), 128.6 (C-4), 128.6 (C-2Ј,6Ј), 129.0 (C-3Ј,5Ј),
132.6 (C-10), 133.4 (C-4Ј), 133.6 (C-9), 137.2 (C-2), 139.5 (C-1Ј).
EI-MS: m/z (%) = 238 (100) [M+·], 202 (43), 176 (6), 119 (12), 101
(19), 88 (9), 75 (4). FAB-HRMS (C16H11Cl [M+H]+): calcd.
238.0549, found 218.0557.
2-Hydroxyphenyl
Ketone (9a): 1H NMR: δ = 3.28 (dd, J = 16.5 and 4.7 Hz, 1 H,
trans-H) 3.39 (dd, J = 16.5 and 10.1 Hz, 1 H, 1cis-H), 4.32 (d, J =
3-Phenyl-4-oxo-1,2,3,4-tetrahydro-2-naphthyl
2-Hydroxyphenyl 3-(4-Nitrophenyl)-2-naphthyl Ketone (5e): Yellow
1
oil. H NMR: δ = 6.77 (ddd, J = 7.7, 7.5 and 0.9 Hz, 1 H, 5Ј-H),
1
7.01 (dd, J = 0.9 and 8.1 Hz, 1 H, 3Ј-H), 7.43 (dd, J = 7.7 and
1.7 Hz, 1 H, 6Ј-H), 7.46 (ddd, J = 8.1, 7.5 and 1.7 Hz, 1 H, 4Ј-H),
7.55 (d, J = 8.8 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.64–7.71 (m, 2 H, 6,7-H),
7.94–8.00 (m, 2 H, 5,8-H), 7.98 (s, 1 H, 1-H), 8.04 (s, 1 H, 4-H),
8.19 (d, J = 8.8 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 11.88 (s, 1 H, 2Ј-OH). 13C
NMR: δ = 118.5 (C-3Ј), 119.0 (C-5Ј), 119.9 (C-1Ј), 123.8 (C-3ЈЈ,5ЈЈ),
127.9 and 128.6 (C-6 and C-7), 128.2 (C-5), 128.6 (C-8), 129.67
(C-2ЈЈ,6ЈЈ), 129.72 (C-1), 130.0 (C-4), 131.8 (C-2), 133.3 (C-6Ј),
133.8 (C-10), 135.2 (C-9) 135.7 (C-3), 137.0 (C-4Ј), 146.8 (C-1ЈЈ),
147.0 (C-4ЈЈ), 163.1 (C-2Ј), 202.6 (C=O). EI-MS: m/z (%) = 369
(100) [M+·], 368 (59), 352 (15), 339 (9), 322 (11), 305 (10), 276 (13),
249 (65), 230 (28), 202 (33), 189 (7), 161 (10), 121 (77), 93 (18), 65
(21). FAB-HRMS (C23H15O4N [M+H]+): calcd. 369.1001, found
369.0989.
10.3 Hz, 1 H, 3-H), 4.62 (ddd, J = 10.3, 10.1 and 4.7 Hz, 1 H, 2-
H), 6.85 (ddd, J = 7.7, 7.5 and 0.9 Hz, 1 H, 5Ј-H), 6.93 (dd, J =
8.4 and 0.9 Hz, 1 H, 3Ј-H), 7.15–7.27 (m, 5 H, 8,2ЈЈ,3ЈЈ,4ЈЈ,5ЈЈ,6ЈЈ-
H), 7.40–7.47 (m, 2 H, 6,4Ј-H), 7.56 (dt, J = 7.5 and 1.3 Hz, 1 H,
7-H), 7.70 (dd, J = 7.5 and 1.3 Hz, 1 H, 6Ј-H), 8.14 (br. d, J =
7.8 Hz, 1 H, 5-H), 12.11 (s, 1 H, 2Ј-OH). 13C NMR: δ = 33.1 (C-1),
48.1 (C-2), 55.6 (C-3), 118.2 (C-1Ј), 118.9 (C-3Ј), 119.1 (C-5Ј), 127.3
(C-4ЈЈ), 127.6 (C-6), 127.9 (C-5), 128.6 (C-8), 128.7 (C-2ЈЈ,6ЈЈ),
128.9 (C-3ЈЈ,5ЈЈ), 129.5 (C-6Ј), 132.2 (C-10), 134.1 (C-7), 137.0
(C-4Ј), 137.9 (C-1ЈЈ), 140.5 (C-9), 163.3 (C-2Ј), 197.0 (C-4), 205.3
(C=O). EI-MS: m/z (%) = 342 (9) [M+·], 322 (5), 221 (100), 191
(5), 178 (5), 165 (5), 121 (53), 91 (24), 77 (5), 65 (20). EI-HRMS
(C23H18O3): calcd. 342.1256, found 342.1251.
2-Hydroxyphenyl
3-(4-Methylphenyl)-4-oxo-1,2,3,4-tetrahydro-2-
2-Phenylnaphthalene (8a): M.p. 94–97 °C (recrystallisation from
naphthyl Ketone (9b): 1H NMR: δ = 2.25 (s, 3 H, 4ЈЈ-CH3), 3.27
(dd, J = 16.5 and 4.9 Hz, 1 H, 1trans-H) 3.37 (dd, J = 16.5 and
1
ethanol). H NMR: δ = 7.39 (t, J = 7.3 Hz, 1 H, 4Ј-H), 7.46–7.54
(m, 4 H, 6,7,3Ј,5Ј-H), 7.58 (d, J = 7.3 Hz, 2 H, 2Ј,6Ј-H). 7.76 (dd, 10.0 Hz, 1 H, 1cis-H), 4.29 (d, J = 10.3 Hz, 1 H, 3-H), 4.61(ddd, J
J = 8.5 and 1.6 Hz, 1 H, 3-H), 7.86–7.92 (m, 2 H, 5,8-H), 7.93 (d, = 10.3, 10.0 and 4.9 Hz, 1 H, 2-H), 6.86 (ddd, J = 7.9, 7.7 and
Eur. J. Org. Chem. 2006, 2558–2569
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A. M. S. Silva et al.
FULL PAPER
1.1 Hz, 1 H, 5Ј-H), 6.94 (dd, J = 8.1 and 1.1 Hz, 1 H, 3Ј-H), 7.05
(s, 4 H, 2ЈЈ,3ЈЈ,5ЈЈ,6ЈЈ-H), 7.25 (d, J = 7.0 Hz, 1 H, 8-H), 7.41 (dd,
J = 7.8 and 7.0 Hz, 1 H, 6-H), 7.45 (ddd, J = 8.1, 7.7 and 1.5 Hz,
(C-5Ј), 127.7 (C-6), 127.9 (C-5), 128.6 (C-8), 128.8 (C-3ЈЈ,5ЈЈ), 129.3
(C-6Ј), 130.4 (C-2ЈЈ,6ЈЈ), 131.9 (C-10), 133.2 (C-4ЈЈ), 134.2 (C-7),
136.3 (C-1ЈЈ), 137.2 (C-4Ј), 140.4 (C-9), 163.4 (C-2Ј), 196.6 (C-4),
1 H, 4Ј-H), 7.54 (dt, J = 7.0 and 1.4 Hz, 1 H, 7-H), 7.72 (dd, J = 204.8 (C=O). EI-MS: m/z (%) = 376 (8) [M+·], 358 (5), 255 (100),
7.9 and 1.5 Hz, 1 H, 6Ј-H), 8.13 (dd, J = 7.8 and 1.4 Hz, 1 H, 5-
220 (6), 191 (13), 165 (6), 121 (77), 90 (27), 65 (28). EI-HRMS
H), 12.13 (s, 1 H, 2Ј-OH). 13C NMR: δ = 21.0 (4ЈЈ-CH3), 33.1 (C-1),
(C23H17O335Cl): calcd. 376.0866, found 376.0857. EI-HRMS
48.0 (C-2), 55.1 (C-3), 118.2 (C-1Ј), 118.9 (C-3Ј), 119.1 (C-5Ј), 127.5 (C23H17O337Cl): calcd. 378.0837, found 378.0832.
(C-6), 127.8 (C-5), 128.5 (C-8), 128.7 (C-2ЈЈ,6ЈЈ), 129.4 (C-3ЈЈ,5ЈЈ),
1
1-Phenylbenzo[c]xanthone (13a): H NMR: δ = 7.37–7.49 (m, 6 H,
129.5 (C-6Ј), 132.2 (C-10), 134.0 (C-7), 134.8 (C-4ЈЈ), 136.85
(C-1ЈЈ), 136.91 (C-4Ј), 140.4 (C-9), 163.2 (C-2Ј), 197.1 (C-4), 205.4
(C=O). EI-MS: m/z (%) = 356 (11) [M+·], 235 (100), 207 (5), 191
(7), 143 (11), 121 (44), 105 (15), 90 (15), 65 (18). EI-HRMS
(C24H20O3): calcd. 356.1412, found 356.1412.
10,2Ј,3Ј,4Ј,5Ј,6Ј-H), 7.55 (s, 1 H, 2-H), 7.68–7.79 (m, 4 H, 5,4,9,8-
H), 7.91 (dd, J = 8.2 and 1.7 Hz, 1 H, 3-H), 8.26 (dd, J = 8.0 and
1.5 Hz, 1 H, 11-H), 8.74 (dd, J = 8.2 and 1.7 Hz, 1 H, 6-H). 13C
NMR: δ = 116.2 (C-12a), 117.5 (C-8), 123.1 (C-6), 123.4 (C-11a),
124.4 (C-10), 126.5 (C-2), 126.8 (C-11), 126.9 (C-5), 127.0 (C-4Ј),
127.6 (C-2Ј,6Ј), 127.9 (C-3), 128.6 (C-3Ј,5Ј), 130.1 (C-4), 131.1
(C-6a), 134.1 (C-9), 135.3 (C-2a), 138.7 (C-1), 142.3 (C-1Ј), 154.9
(C-6b), 155.0 (C-7a), 176.6 (C-12). EI-MS: m/z (%) = 322 (66)
[M+·], 321 (100), 305 (7), 292 (6), 205 (4), 189 (4), 160 (11), 118 (4).
EI-HRMS (C23H14O2): calcd. 322.0994, found 322.0988.
General Procedure for the Synthesis of 2-Hydroxyphenyl 3-Phenyl-2-
naphthyl Ketones 5a-e under Microwave Irradiation: A mixture of
the appropriate 2-hydroxyphenyl 3-phenyl-1,2,3,4-tetrahydro-2-
naphthyl ketone 4a–e (0.235 mmol), DDQ (0.159 g, 0.7 mmol) in
1,2,4-trichlorobenzene (10 mL), in a two-necked glassware appara-
tus, provided with magnetic stirring bar, fiber-optic temperature
control and reflux condenser was heated for 36 minutes according
to the following microwave program: step 1: 6 minutes, ramp to
170 °C, 800 W maximum power; step 2: 30 minutes, hold at 170 °C,
800 W maximum power. The crude product was purified by flash
chromatography on silica gel eluting with light petroleum ether to
remove the 1,2,4-trichlorobenzene and with a 1:1 mixture of light
petroleum ether/dichloromethane to afford the 2-arylnaphthalenes
8a–e (8a, 5%; 8b, 5%; 8c, 4%; 8d, 5%; 8e, 7%), 3-aryl-2-naphthyl
2-hydroxyphenyl ketones 5a–e (5a, 66%; 5b, 65%; 5c, 60%; 5d,
61%; 5e, 44%), 2-hydroxyphenyl 3-phenyl-4-oxo-1,2,3,4-
tetrahydro-2-naphthyl ketones 9a,d (9a, 5%; 9d, 9%). After the elu-
ent was changed to dichloromethane, a mixture of benzoxanthones
was eluted (except for R = NO2, only 1-phenylbenzo[c]xanthone
13e was obtained, 13%). The mixture of benzoxanthones was puri-
fied by preparative TLC eluting with a 8:2 mixture of dichloro-
methane/light petroleum ether, leading to the isolation of 1-aryl-
benzo[c]xanthones 13a–d (13a, 7%; 13b, 8%; 13c, 5%%; 13d, 3%),
2-arylbenzo[c]xanthones 14a–d (14a, 1%; 14b, 4%; 14c, 4%; 14d,
1%), 6-arylbenzo[b]xanthones 15b,c (15b, 2%; 15c, 17%) and 6-
arylbenzo[a]xanthones 16a–d (16a, 5%; 16b, 7%; 16c, 3%; 16d,
4%).
1
1-(4-Methylphenyl)benzo[c]xanthone (13b): H NMR: δ = 2.46 (s, 3
H, 4ЈЈ-CH3), 7.27 (d, J = 7.6 Hz, 2 H, 3Ј,5Ј-H), 7.34 (d, J = 7.6 Hz,
2 H, 2Ј,6Ј-H), 7.39 (dd, J = 7.7 and 7.4 Hz, 1 H, 10-H), 7.54 (s, 1
H, 2-H), 7.67–7.76 (m, 4 H, 4,5,8,9-H), 7.89 (d, J = 7.7 Hz, 1 H,
3-H), 8.27 (dd, J = 7.7 and 1.4 Hz, 1 H, 11-H), 8.73 (d, J = 8.8 Hz,
1 H, 6-H). 13C NMR: δ = 21.4 (4ЈЈ-CH3), 116.1 (C-12a), 117.5
(C-8), 123.0 (C-6), 123.5 (C-11a), 123.7 (C-6a), 124.4 (C-10), 126.5
(C-2), 126.8 (C-5), 126.9 (C-11), 127.8 (C-3), 128.3 (C-2Ј,6Ј), 128.5
(C-3Ј,5Ј), 130.0 (C-4), 134.1 (C-9), 135.3 (C-2a), 138.8 (C-1), 136.4
(C-4Ј), 139.4 (C-1Ј), 154.9 (C-6b), 155.1 (C-7a), 176.6 (C-12). EI-
MS: m/z (%) = 336 (70) [M+·], 335 (100), 319 (9), 305 (5), 167 (7),
161 (19). EI-HRMS (C24H16O2): calcd. 336.1150, found 336.1160.
1
1-(4-Methoxyphenyl)benzo[c]xanthone (13c): H NMR: δ = 3.90 (s,
3 H, 4ЈЈ-OCH3), 7.01 (d, J = 8.7 Hz, 2 H, 3Ј,5Ј-H), 7.37–7.42 (m,
1 H, 10-H), 7.36 (d, J = 8.7 Hz, 2 H, 2Ј,6Ј-H), 7.54 (s, 1 H, 2-H),
7. 69 (dd, J = 8.3 and 1.0 Hz, 1 H, 8-H), 7.71–7.79 (m, 3 H, 4,5,9-
H), 7.89 (dd, J = 7.2 and 1.9 Hz, 1 H, 3-H), 8.28 (dd, J = 7.9 and
1.6 Hz, 1 H, 11-H), 8.73 (dd, J = 8.0 and 1.5 Hz, 1 H, 6-H). 13C
NMR: δ = 55.2 (4ЈЈ-OCH3), 113.0 (C-3Ј,5Ј), 116.0 (C-12a), 117.5
(C-8), 123.0 (C-6), 123.4 (C-6a), 123.7 (C-11a), 124.4 (C-10), 126.6
(C-2), 126.77 (C-11), 126.84 (C-5), 127.9 (C-3), 129.7 (C-2Ј,6Ј),
130.0 (C-4), 134.1 (C-9), 134.6 (C-1Ј), 135.3 (C-2a), 138.4 (C-1),
154.95 (C-6b), 154.99 (C-7a), 158.6 (C-4Ј), 176.8 (C-12). EI-MS:
m/z (%) = 352 (100) [M+·], 351 (87), 337 (11), 309 (16), 292 (7),
279 (17), 252 (5), 169 (10), 154 (18). EI-HRMS (C24H16O3): calcd.
352.1099, found 352.1097.
2-(4-Nitrophenyl)naphthalene (8e): 1H NMR: δ = 8.35 (d, J =
8.8 Hz, 2 H, 3Ј,5Ј-H), 7.54–7.57 (m, 2 H, 6,7-H), 7.88 (d, J =
8.8 Hz, 2 H, 2Ј,6Ј-H), 7.75 (dd, J = 8.6 and 1.5 Hz, 1 H, 3-H),
7.86–7.94 (m, 2 H, 5,8-H), 7.98 (d, J = 8.6 Hz, 1 H, 4-H), 8.11 (d,
J = 1.5 Hz, 1 H, 1-H). 13C NMR: δ = 124.2 (C-3Ј,5Ј), 124.9 (C-3),
126.8 (C-1), 126.8 and 126.9 (C-6 and C-7), 127.7 (C-5), 128.0
(C-2Ј,6Ј), 128.4 (C-8), 129.0 (C-4), 133.2 (C-10) 133.6 (C-9), 136.0
(C-2), 147.1 (C-4Ј), 147.6 (C-1Ј). EI-MS: m/z (%) = 249 (100) [M+·],
219 (10), 202 (59), 191 (10), 176 (5), 152 (5), 101 (11), 88(5). FAB-
HRMS (C16H11NO2 [M+H]+): calcd. 249.0790, found 249.0793.
1
1-(4-Chlorophenyl)benzo[c]xanthone (13d): H NMR: δ = 7.34–7.42
(m, 1 H, 10-H), 7.35 (d, J = 8.3 Hz, 2 H, 3Ј,5Ј-H), 7.43 (d, J =
8.3 Hz, 2 H, 2Ј,6Ј-H), 7.51 (s, 1 H, 2-H), 7. 70 (dd, J = 8.4 and
1.0 Hz, 1 H, 8-H), 7.72–7.80 (m, 3 H, 4,5,9-H), 7.91 (dd, J = 7.0
and 2.2 Hz, 1 H, 3-H), 8.26 (dd, J = 7.9 and 1.6 Hz, 1 H, 11-H),
8.74 (dd, J = 8.3 and 2.0 Hz, 1 H, 6-H). 13C NMR: δ = 115.7
(C-12a), 117.6 (C-8), 123.1 (C-6), 123.2 (C-11a), 123.9 (C-6a), 124.5
(C-10), 126.5 (C-2), 126.7 (C-11), 127.1 (C-5), 127.7 (C-2Ј,6Ј), 127.9
(C-3), 130.0 (C-3Ј,5Ј), 130.2 (C-4), 132.9 (C-4Ј), 134.3 (C-9), 135.2
(C-2a), 137.4 (C-1), 140.7 (C-1Ј), 155.0 (C-6b,7a), 176.7 (C-12). EI-
MS: m/z (%) = 358 (32) [M+·, 37Cl],356 (72) [M+·, 35Cl], 72), 355
(100), 339 (10), 292 (6), 263 (10), 161 (35), 146 (5), 132 (8). EI-
HRMS (C23H13O235Cl): calcd. 356.0604, found 356.0589. EI-
HRMS (C23H13O237Cl): calcd. 358.0575, found 358.0564.
3-(4-Chlorophenyl)-4-oxo-1,2,3,4-tetrahydro-2-naphthyl
2-Hy-
droxyphenyl Ketone (9d): 1H NMR: δ = 3.27 (dd, J = 16.5 and
4.5 Hz, 1 H, 1trans-H) 3.39 (dd, J = 16.5 and 10.8 Hz, 1 H, 1cis-H),
4.32 (d, J = 11.0 Hz, 1 H, 3-H), 4.60 (ddd, J = 11.0, 10.8 and
4.5 Hz, 1 H, 2-H), 6.87 (ddd, J = 7.9, 7.7 and 1.1 Hz, 1 H, 5Ј-H),
6.96 (dd, J = 8.2 and 1.1 Hz, 1 H, 3Ј-H), 7.10 (d, J = 8.5 Hz, 2 H,
2ЈЈ,6ЈЈ-H), 7.23 (d, J = 8.5 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 7.27 (d, J = 6.9 Hz,
1 H, 8-H), 7.42 (dd, J = 7.7 and 7.5 Hz, 1 H, 6-H), 7.47 (ddd, J =
8.2, 7.7 and 1.5 Hz, 1 H, 4Ј-H), 7.57 (ddd, J = 7.5, 6.9 and 1.4 Hz,
1 H, 7-H), 7.70 (dd, J = 7.9 and 1.5 Hz, 1 H, 6Ј-H), 8.13 (dd, J =
1
1-(4-Nitrophenyl)benzo[c]xanthone (13e): H NMR: δ = 7.44 (ddd,
J = 8.0, 7.0 and 1.1 Hz, 1 H, 10-H), 7.54 (s, 1 H, 2-H), 7.57 (d, J
7.7 and 1.4 Hz, 1 H, 5-H), 12.09 (s, 1 H, 2Ј-OH). 13C NMR: δ = = 8.7 Hz, 2 H, 2Ј,6Ј-H), 7.73 (d, J = 8.6 Hz, 1 H, 8-H), 7.78–7.82
33.4 (C-1), 48.0 (C-2), 55.1 (C-3), 118.2 (C-1Ј), 119.0 (C-3Ј), 119.2
(m, 3 H, 5,4,9-H), 7.94 (dd, J = 7.3 and 1.5 Hz, 1 H, 3-H), 8.24
2566
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 2558–2569

Diels–Alder Reactions of 2Ј-Hydroxychalcones with o-Benzoquinodimethane
FULL PAPER
(dd, J = 8.0 and 1.5 Hz, 1 H, 11-H), 8.33 (d, J = 8.7 Hz, 2 H, 3Ј,5Ј- 6-(4-Methylphenyl)benzo[b]xanthone (15b): 1H NMR: δ = 2.54 (s, 3
H), 8.78 (dd, J = 7.9 and 1.4 Hz, 1 H, 6-H). 13C NMR: δ = 115.4 H, 4Ј-CH3), 7.29 (d, J = 8.2 Hz, 1 H, 11-H), 7.33 (dd, J = 7.7 and
(C-12a), 117.7 (C-8), 122.9 (C-3Ј,5Ј), 123.0 (C-11a), 123.2 (C-6), 7.4 Hz, 1 H, 9-H), 7.40 (s, 4 H, 2Ј,3Ј,5Ј,6Ј-H), 7.48–7.55 (m, 2 H,
124.2 (C-6a), 124.8 (C-10), 126.4 (C-2), 126.7 (C-11), 127.7 (C-5),
128.1 (C-3), 129.6 (C-2Ј,6Ј), 130.6 (C-4), 134.6 (C-9), 135.1 (C-2a),
2,3-H), 7.66 (ddd, J = 8.2, 7.4 and 1.7 Hz, 1 H, 10-H), 7.73–7.77
(m, 1 H, 4-H), 8.11–8.14 (m, 1 H, 1-H), 8.37 (dd, J = 7.7 and
136.2 (C-1), 146.8 (C-4Ј), 149.4 (C-1Ј), 155.06 (C-6b), 155.12 1.7 Hz, 1 H, 8-H), 9.00 (s, 1 H, 5-H). 13C NMR: δ = 21.4 (4Ј-CH3),
(C-7a), 176.5 (C-12). EI-MS: m/z (%) = 367 (95) [M+·], 366 (100), 118.2 (C-11), 120.8 (C-7a), 121.1 (C-6a), 123.4 (C-9), 125.3 (C-2),
337 (9), 320 (40), 292 (14), 279 (5), 266 (18), 160 (16), 131 (7),
125.8 (C-4), 126.4 (C-6), 126.8 (C-8), 127.7 (C-5), 128.8 (C-3), 129.1
121 (19), 57 (9). EI-HRMS (C23H13NO4): calcd. 367.0845, found (C-3Ј,5Ј), 129.5 (C-12b), 130.0 (C-1), 130.9 (C-2Ј,6Ј), 131.3 (C-1Ј),
367.0832.
135.1 (C-10), 135.9 (C-4a), 137.5 (C-4Ј), 148.8 (C-12a), 156.7
(C-11a), 178.4 (C-7). EI-MS: m/z (%) = 336 (100) [M+·], 335 (17),
321 (11), 292 (8), 263 (4), 215 (4), 118 (7). EI-HRMS (C24H16O2):
calcd. 336.1150, found 336.1152.
1
2-Phenylbenzo[c]xanthone (14a): H NMR: δ = 7.38–7.54 (m, 6 H,
10,2Ј,3Ј,4Ј,5Ј,6Ј-H), 7.66–7.76 (m, 3 H, 4,5,8-H), 7.82 (ddd, J = 8.4,
6.9 and 1.6 Hz, 1 H, 9-H), 8.01 (dd, J = 8.1 and 1.5 Hz, 1 H, 3-
1
H), 8.24 (s, 1 H, 1-H), 8.44 (dd, J = 8.0 and 1.5 Hz, 1 H, 11-H), 6-(4-Methoxyphenyl)benzo[b]xanthone (15c): H NMR: δ = 3.96 (s,
8.80 (dd, J = 8.7 and 1.6 Hz, 1 H, 6-H). 13C NMR: δ = 117.1 3 H, 4Ј-OCH3), 7.14 (d, J = 8.7 Hz, 2 H, 3Ј,5Ј-H), 7.29 (d, J =
(C-12a), 118.1 (C-8), 121.9 (C-1), 122.5 (C-11a), 123.1 (C-6), 124.4
(C-6a), 124.5 (C-10), 126.6 (C-11), 126.7 (C-3), 126.8 (C-5), 127.6
(C-4Ј), 128.4 (C-2Ј,6Ј), 129.6 (C-4), 130.1 (C-3Ј,5Ј), 134.4 (C-9),
135.1 (C-2a), 136.6 (C-2), 139.5 (C-1Ј), 153.1 (C-6b), 155.8 (C-7a),
176.9 (C-12). EI-MS: m/z (%) = 322 (100) [M+·], 321 (46), 292 (12),
263 (10), 189 (8), 149 (9), 118 (14). EI-HRMS (C23H14O2): calcd.
322.0994, found 322.0990.
8.2 Hz, 1 H, 11-H), 7.34 (ddd, J = 7.9, 7.5 and 0.9 Hz, 1 H, 9-H),
7.43 (d, J = 8.7 Hz, 2 H, 2Ј,6Ј-H), 7.67 (ddd, J = 8.2, 7.5 and
1.7 Hz, 1 H, 10-H), 7.48–7.57 (m, 2 H, 2,3-H), 7.75–7.78 (m, 1 H,
4-H), 8.11–8.14 (m, 1 H, 1-H), 8.37 (dd, J = 7.9 and 1.7 Hz, 1 H,
8-H), 8.99 (s, 1 H, 5-H). 13C NMR: δ = 55.4 (4Ј-OCH3), 113.8
(C-3Ј,5Ј), 118.2 (C-11), 120.8 (C-7a), 121.1 (C-6a), 123.4 (C-9),
125.3 (C-2), 128.9 (C-3), 125.8 (C-4), 126.1 (C-1Ј), 126.5 (C-6),
126.8 (C-8), 127.7 (C-5), 129.6 (C-12b), 130.1 (C-1), 132.2 (C-2Ј,6Ј),
135.2 (C-10), 136.1 (C-4a), 149.0 (C-12a), 156.7 (C-11a), 159.3
(C-4Ј), 178.4 (C-7). EI-MS: m/z (%) = 352 (100) [M+·], 337 (16),
309 (6), 292 (8), 279 (10), 252 (8), 189 (7), 176 (7), 168 (5), 113 (4).
C24H16O3 (352.38): calcd. C 81.80, H 4.58; found C 81.56, H 4.72.
1
2-(4-Methylphenyl)benzo[c]xanthone (14b): H NMR: δ = 2.48 (s, 3
H, 4Ј-CH3), 7.34 (d, J = 8.1 Hz, 2 H, 3Ј,5Ј-H), 7.44 (d, J = 8.1 Hz,
2 H, 2Ј,6Ј-H), 7.48–7.53 (m, 1 H, 10-H), 7.66–7.71 (m, 2 H, 4,5-
H), 7.75 (d, J = 7.8 Hz, 1 H, 8-H), 7.82 (ddd, J = 7.8, 6.9 and
1.5 Hz, 1 H, 9-H), 8.04 (d, J = 7.3 Hz, 1 H, 3-H), 8.23 (s, 1 H, 1-
H), 8.44 (dd, J = 7.9 and 1.5 Hz, 1 H, 11-H), 8.80 (dd, J = 8.3 and
6-Phenylbenzo[a]xanthone (16a): 1H NMR: δ = 7.42 (d, J = 8.0 Hz,
1.6 Hz, 1 H, 6-H). 13C NMR: δ = 21.3 (4Ј-CH3), 117.1 (C-12a), 1 H, 8-H), 7.44 (dd, J = 8.3 and 8.1 Hz, 1 H, 10-H), 7.50–7.65 (m,
118.1 (C-8), 121.8 (C-1), 122.5 (C-11a), 123.1 (C-6), 124.4
(C-6a,10), 126.6 (C-11), 126.7 (C-3), 126.8 (C-5), 129.1 (C-3Ј,5Ј),
129.5 (C-4), 130.0 (C-2Ј,6Ј), 134.4 (C-9), 135.2 (C-2a), 135.9 (C-2),
3 H, 3,3Ј,5Ј-H), 7.65–7.73 (m, 3 H, 9,2Ј,6Ј-H), 7.79 (ddd, J = 8.3,
7.1 and 1.2 Hz, 1 H, 2-H), 7.93 (d, J = 8.0 Hz, 1 H, 4-H), 8.15 (s,
1 H, 5-H), 8.45 (dd, J = 8.1 and 1.6 Hz, 1 H, 11-H), 10.13 (d, J =
136.5 (C-1Ј), 137.4 (C-4Ј), 153.1 (C-6b), 155.8 (C-7a), 177.0 (C-12). 8.3 Hz, 1 H, 1-H). 13C NMR: δ = 115.0 (C-12a), 117.6 (C-8), 123.3
EI-MS: m/z (%) = 336 (100) [M+·], 321 (10), 305 (5), 292 (10), 263 (C-11a), 124.4 (C-10), 126.4 (C-3), 126.5 (C-11), 126.8 (C-1), 128.0
(5), 160 (5), 118 (19). EI-HRMS (C24H16O2): calcd. 336.1150,
found 336.1143.
(C-4Ј), 128.37 (C-2Ј,6Ј), 128.42 (C-4), 129.4 (C-2), 129.8 (C-3Ј,5Ј),
129.9 (C-4a), 130.7 (C-12b), 131.1 (C-6), 133.9 (C-9), 136.6 (C-1Ј),
137.1 (C-5), 154.4 (C-7a), 155.1 (C-6a), 178.8 (C-12). EI-MS:
m/z (%) = 322 (100) [M+·], 321 (16), 294 (18), 265 (12), 245 (7),
205 (10), 181 (14), 168 (6), 121 (12). EI-HRMS (C23H14O2): calcd.
322.0994, found 322.0990.
1
2-(4-Methoxyphenyl)benzo[c]xanthone (14c): H NMR: δ = 3.92 (s,
3 H, 4Ј-OCH3), 7.06 (d, J = 8.5 Hz, 2 H, 3Ј,5Ј-H), 7.47–7.49 (m, 1
H, 10-H), 7.48 (d, J = 8.5 Hz, 2 H, 2Ј,6Ј-H), 7.68–7.74 (m, 2 H,
4,5-H), 7.74 (d, J = 8.2 Hz, 1 H, 8-H), 7.82 (ddd, J = 8.2, 7.1 and
1
1.4 Hz, 1 H, 9-H), 8.04 (d, J = 8.1 Hz, 1 H, 3-H), 8.22 (s, 1 H, 1- 6-(4-Methylphenyl)benzo[c]xanthone (16b): H NMR: δ = 2.50 (s, 3
H), 8.44 (dd, J = 7.9 and 1.4 Hz, 1 H, 11-H), 8.79 (d, J = 8.0 Hz,
1 H, 6-H). 13C NMR: δ = 55.4 (4Ј-OCH3), 113.9 (C-3Ј,5Ј), 117.1 10,8-H), 7.60–7.65 (m, 1 H, 3-H), 7.62 (d, J = 8.1 Hz, 2 H, 2Ј,6Ј-
(C-12a), 118.1 (C-8), 121.8 (C-1), 122.5 (C-11a), 123.1 (C-6), 124.4 H), 7.67–7.73 (m, 1 H, 9-H), 7.79 (ddd, J = 8.2, 7.8 and 1.5 Hz, 1
(C-6a,10), 126.6 (C-11), 126.7 (C-3,5), 129.5 (C-4), 131.2 (C-2Ј,6Ј), H, 2-H), 7.94 (d, J = 8.1 Hz, 1 H, 4-H), 8.15 (s, 1 H, 5-H), 8.46
H, 4Ј-CH3), 7.38 (d, J = 8.2 Hz, 2 H, 3Ј,5Ј-H), 7.43–7.47 (m, 2 H,
131.8 (C-1Ј), 134.4 (C-9), 135.3 (C-2a), 136.3 (C-2), 152.9 (C-6b),
(dd, J = 8.2 and 1.8 Hz, 1 H, 11-H), 10.13 (d, J = 8.2 Hz, 1 H, 1-
155.8 (C-7a), 159.2 (C-4Ј), 177.1 (C-12). EI-MS: m/z (%) = 352 H). 13C NMR: δ = 21.3 (4Ј-CH3), 115.0 (C-12a), 117.7 (C-8), 123.3
(100) [M+·], 337 (28), 309 (10), 279 (15), 252 (6), 176 (11), 169 (5), (C-11a), 124.4 (C-10), 126.4 (C-3), 126.6 (C-11), 126.9 (C-1), 128.4
154 (9). EI-HRMS (C24H16O3): calcd. 352.1099, found 352.1090.
(C-4), 129.1 (C-3Ј,5Ј), 129.3 (C-2), 129.7 (C-2Ј,6Ј), 130.0 (C-4a),
130.7 (C-12b), 131.1 (C-6), 133.7 (C-1Ј), 133.9 (C-9), 136.9 (C-5),
137.9 (C-4Ј), 154.4 (C-7a), 155.3 (C-6a), 178.9 (C-12). EI-MS:
m/z (%) = 336 (100) [M+·], 335 (17), 308 (6), 292 (5), 276 (5), 263
(5), 215 (4), 189 (4), 167 (6), 146 (4). EI-HRMS (C24H16O2): calcd.
336.1150, found 336.1155.
1
2-(4-Chlorophenyl)benzo[c]xanthone (14d): H NMR: δ = 7.47–7.52
(m, 5 H, 10,2Ј,3Ј,5Ј,6Ј-H), 7.71–7.77 (m, 3 H, 4,5,8-H), 7.82 (ddd,
J = 8.2, 7.1 and 1.5 Hz, 1 H, 9-H), 7.95 (d, J = 8.0 Hz, 1 H, 3-H),
8.22 (s, 1 H, 1-H),8.44 (dd, J = 8.0 and 1.5 Hz, 1 H, 11-H), 8.80
(d, J = 8.0 Hz, 1 H, 6-H). 13C NMR: δ = 117.0 (C-12a), 118.2
(C-8), 122.0 (C-1), 122.5 (C-11a), 123.3 (C-6), 124.5 (C-6a), 124.6
(C-10), 126.3 (C-3), 126.6 (C-11), 126.9 (C-5), 128.7 (C-2Ј,6Ј), 129.8
1
6-(4-Methoxyphenyl)benzo[c]xanthone (16c): H NMR: δ = 3.94 (s,
3 H, 4Ј-OCH3), 7.10 (d, J = 8.6 Hz, 2 H, 3Ј,5Ј-H), 7.44–7.47 (m, 2
(C-4), 131.4 (C-3Ј,5Ј), 133.8 (C-4Ј), 134.5 (C-9), 134.9 (C-2a), 135.3 H, 10,8-H), 7.63 (dd, J = 8.1 and 7.4 Hz, 1 H, 2-H), 7.67 (d, J =
(C-2), 137.9 (C-1Ј), 153.2 (C-6b), 155.8 (C-7a), 176.9 (C-12). EI-
MS: m/z (%) = 358 (46) [M+·, 37Cl], 356 (100) [M+·, 35Cl], 355 (22),
320 (15), 292 (20), 263 (16), 189 (6), 161 (10), 132 (7). EI-HRMS
(C23H13O235Cl): calcd. 356.0604, found 356.0595. EI-HRMS
(C23H13O237Cl): calcd. 358.0575, found 358.0573.
8.6 Hz, 2 H, 2Ј,6Ј-H), 7.71 (ddd, J = 8.0, 7.1 and 1.4 Hz, 1 H, 9-
H), 7.79 (dd, J = 8.0 and 7.4 Hz, 1 H, 3-H), 7.94 (d, J = 8.0 Hz, 1
H, 4-H), 8.14 (s, 1 H, 5-H), 8.47 (dd, J = 8.2 and 1.4 Hz, 1 H, 11-
H), 10.13 (d, J = 8.1 H, 1 Hz, 1-H). 13C NMR: δ = 55.4 (4Ј-OCH3),
113.8 (C-3Ј,5Ј), 115.2 (C-12a), 117.6 (C-8), 123.2 (C-11a), 124.4
Eur. J. Org. Chem. 2006, 2558–2569
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2567

A. M. S. Silva et al.
FULL PAPER
[9]
G. M. Kitanov, P. T. Nedialkov, Phytochemistry 2001, 57, 1237–
(C-10), 126.7 (C-1,3,11), 127.8 (C-1Ј), 128.3 (C-4), 129.2 (C-2),
130.4 (C-4a,6,12b), 131.1 (C-2Ј,6Ј), 133.8 (C-9), 136.7 (C-5), 154.4
(C-7a), 155.3 (C-6a), 159.5 (C-4Ј), 179.1 (C-12). EI-MS: m/z (%) =
352 (100) [M+·], 337 (16), 309 (17), 279 (6), 252 (7), 176 (8), 154
(4). EI-HRMS (C24H16O3): calcd. 352.1099, found 352.1098.
1243.
[10]
S. Rancon, A. Chaboud, N. Darbour, G. Comte, C. Bayet, P.-
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[12]
6-(4-Chlorophenyl)benzo[a]xanthone (16d): 1H NMR: δ = 7.42–7.47
(m, 2 H, 10,8-H), 7.54 (d, J = 8.5 Hz, 2 H, 2Ј,6Ј-H), 7.61–7.67 (m,
1 H, 3-H), 7.66 (d, J = 8.5 Hz, 2 H, 3Ј,5Ј-H), 7.72 (dt, J = 7.7 and
1.7 H, 1 Hz, 9-H), 7.82 (ddd, J = 8.3, 7.8 and 1.4 Hz 1 H, 2-H),
7.95 (d, J = 8.0 Hz, 1 H, 4-H), 8.14 (s, 1 H, 5-H), 8.47 (dd, J = 8.0
and 1.7 Hz, 1 H, 11-H), 10.14 (d, J = 8.3 Hz, 1 H, 1-H). 13C NMR:
δ = 114.9 (C-12a), 117.5 (C-8), 123.3 (C-11a), 124.6 (C-10), 126.55
(C-11), 126.63 (C-3), 126.9 (C-1), 128.5 (C-4), 128.6 (C-2Ј,6Ј), 129.7
(C-2), 129.8 (C-12b), 129.9 (C-4Ј), 130.8 (C-4a), 131.6 (C-3Ј,5Ј),
134.0 (C-9), 134.2 (C-1Ј), 135.1 (C-6), 136.9 (C-5), 154.4 (C-7a),
154.9 (C-6a), 178.8 (C-12). EI-MS: m/z (%) = 358 (3) [M+·, 37Cl],
356 (2) [M+·, 35Cl], 255 (100), 220 (5), 202 (3), 191 (7), 165 (5), 121
(58), 90(15), 65 (13). EI-HRMS (C23H13O235Cl): calcd. 356.0604,
found 356.0605. EI-HRMS (C23H13O237Cl): calcd. 358.0575, found
358.0586.
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M. Meloun, T. Syrový, A. Vrána, Talanta 2004, 62, 511–522.
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Acknowledgments
[16]
[17]
[18]
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Sincere thanks are expressed to the University of Aveiro, “Fun-
dação para a Ciência e a Tecnologia”, Portugal, and FEDER for
funding the Organic Chemistry Research Unit. C.M.B. thanks the
Organic Chemistry Research Unit for a research grant.
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Selected data for 1-(4-methylphenyl)-1,2-dihydrobenzo[c]xan-
thone (6b) (11%): 1H NMR: δ = 2.20 (s, 3 H, 4Ј-CH3), 3.16
(dd, J = 16.0 and 1.2 Hz, 1 H, H-2trans), 3.53 (dd, J = 16.0 and
7.5 Hz, 1 H, H-2cis), 4.70 (d, J = 7.5 Hz, 1 H, H-1), 6.93 (d, J
= 8.1 Hz, 2 H, H-3Ј,5Ј), 7.07 (d, J = 8.1 Hz, 2 H, H-2Ј,6Ј),
7.20–7.23 (m, 1 H, H-3), 7.35–7.41 (m, 3 H, H-4,5,10), 7.58 (d,
J = 7.8 Hz, 1 H, H-8), 7.68 (dt, J = 7.8 and 1.7 Hz, 1 H, H-9),
8.04–8.07 (m, 1 H, H-6), 8.21 (dd, J = 8.0 and 1.7 Hz, 1 H,
H-11). 13C NMR: δ = 20.9 (4Ј-CH3), 34.3 (C-1), 35.0 (C-2),
117.9 (C-8), 119.2 (C-12a), 123.86 (C-6), 123.90 (C-11a), 124.8
(C-10), 126.0 (C-11), 127.0 and 131.5 (C-4 and C-5), 127.1
(C-2Ј,6Ј), 128.3 (C-6a), 128.95 (C-3), 129.01 (C-3Ј,5Ј), 133.4
(C-9) 136.1 (C-4Ј), 137.8 (C-2a), 139.6 (C-1Ј), 155.6 (C-7a),
158.0 (C-6b), 176.8 (C-12). EI-MS: m/z (%) = 338 (95) [M+·],
337 (86), 247 (100), 218 (16), 202 (14), 189 (18), 105 (10), 91
(12), 77 (6), 65 (7).
[22]
Selected data for xanthones 7d. 1-(4-chlorophenyl)-8-iodo-1,2-
1
dihydrobenzo[c]xanthone (7d1) (7%): H NMR: δ = 3.14 (dd,
J = 16.3 and 1.2 Hz, 1 H, H-2trans), 3.55 (dd, J = 16.3 and
7.9 Hz, 1 H, H-2cis), 4.67 (dd, J = 7.9 and 1.2 Hz, 1 H, H-1),
7.10 (s, 4 H, H-2Ј,3Ј,5Ј,6Ј), 7.13 (dd, J = 7.8 and 1.5 Hz, 1 H,
H-9), 7.16 (t, J = 7.8 Hz, 1 H, H-10), 7.21–7.24 (m, 1 H, H-3),
7.44–7.47 (m, 2 H, H-4,5), 8.18 (dd, J = 7.8 and 1.5 Hz, 1 H,
H-11), 8.24–8.27 (m, 1 H, H-6).
(4-Chlorophenyl)-10-iodo-1,2-dihydrobenzo[c]xanthone (7d2)
(6%): 1H NMR: δ = 3.13 (dd, J = 16.2 and 1.1 Hz, 1 H,
H-2trans), 3.53 (dd, J = 16.2 and 7.9 Hz, 1 H, H-2cis), 4.68 (dd,
J = 7.9 and 1.1 Hz, 1 H, H-1), 7.09 (s, 4 H, H-2Ј,3Ј,5Ј,6Ј), 7.21–
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2568
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 2558–2569

Diels–Alder Reactions of 2Ј-Hydroxychalcones with o-Benzoquinodimethane
FULL PAPER
(m, 2 H, H-4,5), 7.95 (dd, J = 8.8 and 2.2 Hz, 1 H, H-9), 8.01–
8.04 (m, 1 H, H-6), 8.53 (d, J = 2.2 Hz, 1 H, H-11).
(4-Chlorophenyl)-8,10-diiodo-1,2-dihydrobenzo[c]xanthone
(7d3) (13%): 1H NMR: δ = 3.14 (br. d, J = 16.3 Hz, 1 H,
H-2trans), 3.54 (dd, J = 16.3 and 8.0 Hz, 1 H, H-2cis), 4.65 (dd,
J = 8.0 and 1.2 Hz, 1 H, H-1), 7.09 (s, 4 H, H-2Ј,3Ј,5Ј,6Ј), 7.22–
7.25 (m, 1 H, H-3), 7.44–7.47 (m, 2 H, H-4,5), 8.19–8.22 (m, 1
H, H-6), 8.39 (d, J = 2.1 Hz, 1 H, H-9), 8.47 (d, J = 2.1 Hz, 1
H, H-11).
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www.eurjoc.org
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