The synthesis of novel p-quinone methides: O-dealkylation of 5-(p-alkyloxyaryl)-10,11-dihydrodibenzo[a,d]cyclohepten-5-ols and related compounds

Article abstract of DOI:10.1002/ejoc.200400754

The synthesis of a series of novel tricyclic p-quinone methides (p-QMs) from 5-(p-alkyloxyaryl)-10,11-dihydrodibenzo[a,d]cyclohepten-5-ol and related substrates in moderate-to-good yields is reported. The reaction is proposed to proceed under mild acidic conditions by O-dealkylation of the p-alkoxy group on the p-position of the pendant 5-aryl ring on the B-ring of the tricyclic system.The effect of different alkyl groups on the oxygen atom, as well as substituent groups on the phenyl ring flanking the O-alkyl group has also been investigated The mechanism of the reaction is discussed in terms of the relatively high intermediate cation stabilities, the possible intermediacy of a hemiketal, as well as conformational effects. Various modifications to the central seven-membered B-ring to introduce more rigidity to the tricyclic system have been made and the scope of the reaction further elaborated. Furthermore, the single crystal structure of dienone 14 has been determined and the p-quinone methide shown to be non-planar, which would account for the relative conformational rigidity of these systems and their ability to accommodate the planar cyclohexa-2,5-dienone moiety and thus explain the stability of these systems relative to their 5- and six-membered B-ring counterparts. These compounds may be useful for the synthesis of novel dyes or compounds which may exhibit photochromic and thermochromic properties. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).

Full text of DOI:10.1002/ejoc.200400754

FULL PAPER
The Synthesis of Novel p-Quinone Methides: O-Dealkylation of
5-(p-Alkyloxyaryl)-10,11-dihydrodibenzo[a,d]cyclohepten-5-ols and Related
Compounds
Benjamin Taljaard,*[a] Jana H. Taljaard[a] Christopher Imrie[a] and Mino R. Caira[b]
Keywords: Cleavage reactions / Conjugation / Dealkylation / Medium-ring compounds / Quinone methides / Dienones
The synthesis of a series of novel tricyclic p-quinone me- tricyclic system have been made and the scope of the reac-
thides (p-QMs) from 5-(p-alkyloxyaryl)-10,11-dihydrodi-
benzo[a,d]cyclohepten-5-ol and related substrates in moder-
ate-to-good yields is reported. The reaction is proposed to
proceed under mild acidic conditions by O-dealkylation of
the p-alkoxy group on the p-position of the pendant 5-aryl
ring on the B-ring of the tricyclic system.The effect of dif-
ferent alkyl groups on the oxygen atom, as well as substitu-
ent groups on the phenyl ring flanking the O-alkyl group
has also been investigated The mechanism of the reaction is
discussed in terms of the relatively high intermediate cation
stabilities, the possible intermediacy of a hemiketal, as well
as conformational effects. Various modifications to the cen-
tral seven-membered B-ring to introduce more rigidity to the
tion further elaborated. Furthermore, the single crystal struc-
ture of dienone 14 has been determined and the p-quinone
methide shown to be non-planar, which would account for
the relative conformational rigidity of these systems and their
ability to accommodate the planar cyclohexa-2,5-dienone
moiety and thus explain the stability of these systems relative
to their 5- and six-membered B-ring counterparts. These
compounds may be useful for the synthesis of novel dyes or
compounds which may exhibit photochromic and thermo-
chromic properties.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
aromatic alkenes have been shown to have thermochromic
properties and thus used as thermochromic dyes.[17–23] Para-
extended p-QMs have also been synthesized and studied as
electron acceptors for the production of organic conducting
materials.[24]
The synthesis of p-QMs derived from triarylmethyl (tri-
tyl) systems, the fuchsones, by the O-demethylation of
methoxyphenyl trityl alcohols or chlorides under strongly
acidic conditions at relatively high temperatures has been
reported more than a century ago.[25–27] More recently
Wada and co-workers, using trifluoroacetic acid instead of
conc. sulfuric acid, obtained considerably higher yields of
these useful dienones under much milder reaction condi-
tions.[28] However, the synthesis of tricyclic p-QMs from
ring systems containing seven-membered central B-rings
under the above reaction conditions, has not as yet been
reported.
The theoretical and stereochemical aspects, the UV and
IR spectra of simple p-QMs derived from trityl systems had
been studied in detail, but their synthetic uses or chemical
reactions have surprisingly not been that well documen-
ted.[29–35] Furthermore, the simplest p-QM, 4-methylene-cy-
clohexa-2,5-dienone, has eluded isolation until only fairly
recently, when it was trapped by complex formation with
metals.[36,37]
Introduction
p-Quinone methides (p-QMs) are important intermedi-
ates in the biosynthesis of lignin,[1] as well as various other
biological processes,[2–5] and were also identified as key in-
termediates in the formation of the toxic butylated hy-
droxytoluene found in food preservatives.[6] They occur in
plants and were implicated as transient intermediates in the
biosynthesis of chemical constituents of various natural
products.[7–9] p-Quinone methides, which are usually in-
tensely coloured, form the backbone of various cationic
dyes and pH-sensitive indicators, such as fluorescein, which
has found application as a diagnostic aid for cornea
trauma, as well as analytical reagents such as bromophenol
blue, a pH-sensitive indicator, and eosin, a wool dye and a
histological staining agent for muscular fibers.[10–14] Syn-
thetic flavylium salts can be utilized as molecular level
switches driven by pH changes accompanied by dramatic
colour changes as a result of the intermediacy of quinone
methides,[15,16] whereas p-QMs and overcrowded bistricyclic
[a] Department of Chemistry, University of Port Elizabeth,
P. O. Box 1600, Port Elizabeth 6000, South Africa
Fax: +27-41-5042573
E-mail: benjamin.taljaard@nmmu.ac.za
[b] Department of Chemistry, University of Cape Town,
Rondebosch 7701, Cape Town, South Africa
E-mail: xraymino@science.uct.ac.za
Tricyclic analogues based on fluorene and xanthene, have
also not as yet been successfully synthesized by any of these
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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DOI: 10.1002/ejoc.200400754
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FULL PAPER
acid-mediated methods, although fluorenyl derivatives were O-dealkylation reaction outlined in Scheme 1. In addition,
prepared using Wittig reaction methodology, as well as by the single crystal structure of the p-QM, 14 has been deter-
oxidative methods, requiring either anhydrous or rather mined (Figure 2).
drastic reaction conditions.[38,39] However, the synthesis of
4-(dibenzo[a,d]cyclohepten-5-ylidene)cyclohexa-2,5-dienone
(14) by deprotonation of the 5-(p-hydroxyphenyl)di-
Results and Discussion
benzo[a,d]cyclohepten-5-ylium salt with triethylamine, has
been reported.[40]
Following our good results on the synthesis of com-
We have previously reported the synthesis of the two pounds 1 and 2, it was decided to focus on a systematic
novel tricyclic seven-membered B-ring p-QMs, 4-(6H-di- study of the synthesis of these interesting novel compounds
benzo[b,e]thiepin-11-ylidene)cyclohexa-2,5-dienone (1) and in order to determine the scope of the reaction, starting
its oxygen analogue 2 under relatively mild reaction condi- with relatively easily accessible starting materials. The
tions (Figure 1).[41] We now report on the synthesis of a ketones 3 and 4 (Scheme 1) were either purchased or syn-
range of novel tricyclic p-QMs containing central seven- thesized in our laboratories by well-established proto-
membered rings where, in the latter compounds, the hetero- cols[42–44] and these and other ketones derived from 4 syn-
atoms in 1 and 2 have been substituted by carbon atoms thesized and subsequently converted into the corresponding
and a couple of carbocyclic ring systems. A few trityl ana- p-methoxyaryl alcohols using Grignard reaction methodol-
logues have also been included to illustrate the versatility of ogy.[45,46]
this mild synthetic procedure and we also elaborate further
In some cases, Grignard reactions gave modest yields of
on aspects of the mechanism previously proposed for the the corresponding tertiary benzylic alcohols as pure gums,
which could not be induced to crystallize. Substantial
amounts of the aryl–aryl coupling product, 4,4Ј-dimethoxy-
1,1Ј-diphenyl, were isolated from the latter reaction mix-
tures. These aryl coupling products have also previously
been obtained in Grignard reactions and the synthetic util-
ity of these aryl couplings exploited.[47,48] Moreover, struc-
turally similar tricyclic alcohols are known to form enclath-
ration compounds with both diethyl ether and THF, the
reaction solvents employed in the classical preparations of
the Grignard reagents, thus accounting for the reluctance
of these alcohols to crystallize.[49–51]
Treatment of these alcohols with trifluoroacetic acid, in
Figure 1. 4-(6H-dibenzo[b,e]thiepin-11-ylidene)cyclohexa-2,5-dien-
the presence of a small amount of water, at ambient tem-
perature for 2 days, followed by aqueous alkaline work-up
and preparative thin-layer chromatographic (PLC) separa-
tion, gave the p-QMs in poor-to-excellent non-optimised
yields. The relatively modest yields of p-QMs in some cases
may be attributed to mechanical losses due to the extensive
PLC separations necessary for the isolation of the required
substrates from the complex reaction mixtures.
one and its oxygen analogue.
In order to assess the effect of groups other than meth-
oxy on the para-position of the pendant 5-aryl group on the
O-dealkylation reaction, various alkyl leaving groups were
introduced into 3 as model compound (5a–5d, Scheme 2).
It was surmised that the higher cation stability of the leav-
ing benzyl and p-chlorobenzyl groups would enhance the
yields of p-QM 6 if the mechanism involved nucleophilic
attack on the departing alkyl group due to the relatively
high stability of the benzyl cations. However, even though
yields were not optimised, the methoxy group gave the best
overall yield (Scheme 2), further suggesting the formation
of a hemiketal intermediate during the course of the reac-
tion. Furthermore, as appropriate p-methoxyphenyl deriva-
tives are more accessible and cheaper than other alkoxyl
substituents, these derivatives were selected as the reagents
of choice for our synthetic studies.
Scheme 1. Synthesis of novel tricyclic p-quinone methides. Rea-
gents and reaction conditions: i. p-MeOC6H4MgBr, THF; ii. aque-
ous NH4Cl; iii. trifluoroacetic acid, H2O, 2 days, room temp.; iv.
aqueous NaOH work-up.
The effect of various groups flanking the methoxyl group
on the p-position of the pendant phenyl ring have been in-
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The Synthesis of Novel p-Quinone Methides
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in the seven-membered B-ring systems, the conformational
barriers are suggested to be much higher and hence would
account for the higher stability and reluctance of these sys-
tems to revert to the phenolic forms in basic medium.
Scheme 2. Synthesis of alcohols 5a–5d: Effect of various alkyl
groups on the aryl-oxygen atom on the O-dealkylation reaction.
Reagents and conditions: i. p-ROC6H4MgBr (R = methyl, n-butyl)
or p-ROC6H4MgCl (R = benzyl, p-chlorobenzyl), THF, reflux; ii.
aqueous NH4Cl; iii. CH2Cl2, CF3CO2H, H2O, room temp., 2 days;
iv. aqueous NaOH work-up.
vestigated next (Scheme 3). In all cases, good-to-excellent
yields of p-QMs were obtained and, although lower overall
yields of dienones 8a–8c were obtained, the methoxy leav-
ing group still gave the best results (see compounds 5a and
8a). No evidence could be obtained for demethylation of
the meta-methoxy group on the phenyl ring linked to the 5-
position. This result would suggest that the generation of
an incipient stable benzylic carbocation at the latter carbon
atom is the pivotal intermediate step for p-QM formation
and that the O-demethylation reaction of the p-methoxy
group is driven by the added stabilization of this cation in-
curred on demethylation, introducing more conjugation to
Scheme 3. The effect of different O-aryl groups at C-5 of 5-(4Ј-O-
alkylaryl)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ol on p-
QM formation. Reagents and conditions: i. ArMgBr, THF, 5 h re-
flux; ii. aqueous NH4Cl; iii. CF3CO2H, H2O, CH2Cl2, room temp.,
2 days; iv. aqueous NaOH work-up.
The alcohol 7a dealkylated smoothly to give the p-QM,
form a very stable dienone ring. In contrast to the planar 8a in excellent yield. This compound was targeted as a pos-
fluorenyl[52] and reasonably planar and conformationally sible key intermediate for our planned annulation of the
more mobile 9H-xanthenyl, 9H-thioxanthenyl, 9H-thioxan- dienone system for the synthesis of tricyclic strained al-
thenyl-10,10-dioxide, N-benzyl-9,10-dihydroacridinyl, and kenes, as it already has a phenyl ring annulated to the dien-
9,10-dihydroanthracenyl tricyclic moieties, where the one system.
formed cyclohexa-2,5-dienone ring is expected to be sub-
In order to provide further evidence for our proposal of
jected to more severe steric interactions as a result of peri- the importance of the formation of a stable cation at C-5
1,8-hydrogen interactions of the annulated A and B benzene (structure 9, Scheme 4) as driving force for the demethyla-
rings, the seven-membered ring systems may assume confor- tion, alcohol 5a was reduced to the corresponding hydro-
mations in which the dienone ring may readily be accom- carbon, thereby inhibiting the cation formation capability
modated.[53–55] In contrast, in the open ring system of di- at this position of the substrate (Scheme 4).
phenyl(p-methoxyphenyl)methanols (tritanols), the aryl
The pivotal role of the formation of a carbocation at C-
rings are twisted out of plane and the assumed conforma- 5 was demonstrated by the conversion of the alcohol 5a to
tions of the formed p-QM may also readily accommodate the corresponding hydrocarbon 10 (Scheme 4). The hydride
the formed cyclohexa-2,5-dienone moiety, but may also rel- ion, being a very poor leaving group, especially in acid me-
atively easily revert back to the phenolic structure, whereas dium, expectedly, did not result in the formation of the in-
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Scheme 4. The effect of a stable carbocation at C-5 of compound
5a on the O-dealkylation reaction. Reagents and conditions: i.
HClO4/Ac2O/CH2Cl2, ether and petroleum ether added to precipi-
tate the perchlorate salt; ii. CF3CO2H, H2O, room temp., 2 days;
iii. HCO2H, Na2CO3, reflux for 1 h.
tensively coloured cation under the prevailing low pH con-
ditions of the dealkylation reaction. Subsequently no evi-
dence could be obtained for p-QM formation. However, on
treatment of the anhydrous perchlorate salt 9,[56] immedi-
ately after its synthesis, with aqueous trifluoroacetic acid,
afforded p-QM 6 in 72% yield. As had been suggested pre-
viously,[41] the reaction proceeds either by the intermediacy
of a hemiketal intermediate, followed by elimination of
methanol to form the p-QM, or via direct attack of a nu-
cleophile on the protonated O-methoxy carbon atom
(Scheme 5, pathway B).
Scheme 5. Proposed mechanism for the O-dealkylation of 5H-(5-p-
methoxyphenyl)dibenzo-10,11-dihydro[a,d]cyclohepten-5-ol (5a).
Reagents and conditions: CF3CO2H, H2O, 2 days stirring at ambi-
ent temperature, aqueous basic work-up.
Clearly, both conformational and steric effects play a sig-
nificant role in the formation and stablity of the p-QM, ac-
counting for the more conformationally restricted tricyclic
systems to form stable p-QMs.
Furthermore, no evidence could be obtained for in- much higher, resulting in a greater reluctance of these p-
terconversion of the coloured dienone to the corresponding QMs to undergo reversion to the phenolic form in the pres-
colourless phenolic form in aqueous basic medium, as had ence of aqueous sodium hydroxide.
been reported to occur in trityl systems.[14,15,37] Although
The 300-MHz 1H-NMR spectra of the oxygen and sulfur
low yields of fuchsones were expected due to losses of pro- analogues 1 and 2, respectively, showed no change on re-
duct on work-up as consequence of this phenomenon, a few cording the spectra over the temperature range –50 °C to
of the latter compounds were synthesized under the present +120 °C. This behaviour contrasts sharply with that of the
reaction conditions. Quite acceptable yields of the p-qui- alcohol precursors where the doublet AB coupling systems,
nones (fuchsones) were obtained even in spite of this re- assigned to the non-equivalent benzylic protons in the cen-
ported rapid keto-enol interconversion occurring in the lat- tral B-ring α to the heteroatom, coalesced to broad singlets
ter conformationally more mobile trityl systems. These on heating, further supporting our proposal for relatively
yields are depicted in Scheme 6.
high energy barriers to conformational interchange to be
The more rigid tricyclic systems used in our investi- present in these p-QMs.[57] No changes were observed in
1
gations are non-planar and energy barriers for the intercon- the H NMR spectra of the p-QMs reported here over the
version of the various conformations are surmised to be specified temperature range.
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The Synthesis of Novel p-Quinone Methides
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Scheme 6. Synthesis of fuchsones under O-dealkylation reaction
conditions. Reagents and reaction conditions: i. ArMgBr, THF, 18
h, reflux; ii. aqueous NH4Cl; iii. trifluoroacetic acid, H2O, room
temp., 2 days; iv. aqueous NaOH work-up.
In order to further restrict the conformational lability of
the molecule and to broaden the scope of the reaction, a
double bond and other substituents were systematically in-
troduced into the central seven-membered ring (Schemes 7–
9). Introduction of a double bond at C-10–C-11, gave p-
QM 14 in 55% yield (Scheme 7). Dealkylation of the p-
allyloxyphenyl alcohol 15 also afforded 14 in 56% yield, the
allyloxy leaving group showing no distinct advantage over
the p-methoxy substituent. Introduction of a bromine atom
on a double bond carbon atom of the bridge, gave the cor-
responding p-QM 19 in excellent yield (84%, see Scheme 7).
Scheme 7. Effect of the introduction of a double bond at the 10,11-
position of 5-(p-methoxyhenyl)-10,11-dihydro[a,d]cyclohepten-5-ol
on the demethylation reaction. Reagents and reaction conditions:
i. Br2, AcOH, room temp., overnight stirring; ii. KOH, MeOH, 2
h reflux; iii. p-MeOC6H4MgBr, THF, reflux, 16 h; iv. aqueous
NH4Cl; v. trifluoroacetic acid, H2O, room temp., 2 days, aqueous
NaOH work-up; vi. allylmagnesium bromide, THF, 16 h reflux; vii.
aqueous NH4Cl.
The introduction of a cyclopropyl moiety annulated to (Scheme 9). The additional benzene ring at the 10,11-posi-
the 10,11-carbons, gave an acceptable yield of p-QM 22 tion intoduced additional strain into the molecule as a re-
(Scheme 8). The cyclopropyl moiety, despite introducing sult of peri-interactions of the 1,8-aryl hydrogen atoms of
additional steric strain in the system,[58] does not seem to the tricyclic system with the planar cyclohexadienone ring,
impart a significant effect on the yield of product 22. Al- thereby increasing the energy barrier for conformational in-
though the stereochemistry of the precursor alcohol and the version of the molecule. Although good yields of the
dienone, respectively, have not been determined, modelling alcohols 24 and 27 were obtained, the tetracyclic alcohol 24
studies suggest that the conformation in which the cis-fused gave the corresponding p-QM in low yield (23%). This may
cyclopropyl ring is in an anti-orientation with respect to to be attributed to the relatively low stability of the formed
the cyclohexadienone moiety on the seven-membered B- cation due to the decreased stabilization as a result of the
ring, to be the most stable.
aromatic system twisted out of plane, whereby resonance
The ketones 23 and 26 were synthesized next by well- stabilization is inhibited.[61] The tetracyclic compound 27
established methods,[59–61] converted into the corresponding however, gave Ͻ1% of dienone and a plethora of side-prod-
alcohols, and, subsequently to the p-QMs in the usual way ucts, attributed to the instability of the latter alcohol in acid
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Scheme 8. Synthesis of 4-(1,1-dichloro-1,1a,6,10b-tetrahydrodi-
benzo[a,e]cyclopropa[c]dibenzo[a,d]cyclohepta-5-ylidene)cyclohexa-
2,5-dione. Reagents and conditions: i. CCl3CO2Et, powdered Na-
OMe, benzene/petroleum ether, 0–5 °C; ii. p-MeOC6H4MgBr, 16 h;
iii. aqueous NH4Cl; iv. CF3CO2H, H2O, 2 days, room temp.; v.
aqueous NaOH work-up.
medium. Reducing the reaction time of the alcohol 27 with
trifluoroacetic acid to 2 h, gave 28 in 20% yield, as well as
starting material (65%). However, treatment of p-QM, 19,
with KOtBu in ethereal furan by published methods,[59,60]
afforded an improved yield of 28 (54%).
In order to explain the relatively high stability of the tri-
cyclic seven-membered p-QMs as compared to the corre-
sponding 5- and six-membered systems, the X-ray crystal Scheme 9. Synthesis of 4-(tribenzo[a,c,e]cyclohepten-9-ylidene)cy-
clohexa-2,5-dione. Reagents and reaction conditions: i. p-Me-
structure of dienone 14 was determined (Figure 2 and Fig-
OC6H4MgBr, 5 h; ii. aqueous NH4Cl; iii. CF3CO2H, H2O, 2 days,
room temp.; iv. aqueous NaOH work-up.
ure 3). These clearly show that the molecule may assume a
conformation which will allow for the dienone system to
be accommodated without much steric interaction. In the
respective conformationally more labile and essentially
planar xanthenyl and planar fluorenyl systems, respectively,
steric interactions are expected to hinder formation of the
planar cyclohexadienone ring, which would also account
for the resistance of these systems to O-demethylate under
the prevailing mild reaction conditions employed in our in-
vestigations.
Figure 2 shows the structure and conformation of 14 de-
termined by X-ray analysis. The molecular point symmetry
deviates only slightly from Cs. Atoms C10, C11, C14, and
C15 form a plane with the remaining atoms of the seven-
membered ring located above it. The endocyclic torsion
angles around bonds C10–C11 and C14–C15 are 4.1(2) and
0.0(2)°, respectively, and ring symmetry is reflected in the
remaining pairs of torsion angles viz. those about C11–C12,
C13–C14 [34.3(2), –35.6(2)°] and about C9–C10, C9–C15
[–65.2(1), 62.9(1)°]. A formal double bond is confirmed for
C12–C13, 1.338(2) Å, and the torsion angle around this
bond is –0.6(2)°. As a result of the conformation adopted thermal ellipsoids at the 50% probability level.
Figure 2. X-ray structure of 14 showing atomic numbering and
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The Synthesis of Novel p-Quinone Methides
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membered tricyclic B- ring analogues to demethylate to
form stable, isolable, p-quinone methides under the pre-
vailing mild acidic reaction conditions. Furthermore, these
compounds should provide an entry into new photochro-
mic and thermochromic materials and dyes.
Further investigations of reactions of these interesting
compounds, as well as the scope of the dealkylation reac-
tion are currently being pursued.
Experimental Section
Melting points were determined on an Electrothermal IA900 series
digital melting point apparatus and are uncorrected. Infrared spec-
tra were recorded on a Perkin–Elmer 1600 Series Fourier Trans-
1
form Spectrometer. H (300 MHz) and 13C (75 MHz) NMR spec-
tra were recorded on a Bruker Avance 300 NMR spectrometer.
All spectra were recorded in CDCl3, unless otherwise stated and
chemical shifts are expressed in ppm relative to TMS as internal
standard.
Figure 3. Projection of the crystal structure of 14 down (001).
High resolution mass spectra (EI, 70 eV) were determined on a
Kratos MS80RF instrument in the analytical laboratories of the
Cape Technikon, Cape Town, South Africa and the X-ray structure
determination was done by the X-ray unit at the University of Cape
Town, South Africa.
by the central ring, the tricyclic system has a concave shape
with a dihedral angle between the phenyl ring planes of
58.2(1)°.
The ring C16 through C21 is planar (max. deviation from
the LS-plane = 0.004 Å) and is confirmed as a cyclohexa-
diene system with bonds C17–C18 and C20–C21 equal
1.344(2), 1.340(2) Å and significantly shorter than the re-
maining four bonds [range 1.455(2)–1.460(2) Å]. Double
bond character for C9–C16, 1.367(2) Å, is also confirmed.
Slight deviation from Cs symmetry is indicated by non-zero
values for the torsion angles C15–C9–C16–C17, 6.4(2)° and
C10–C9–C16–C21, 1.6(2)°.
Preparative thin-layer chromatography (PLC) separations were car-
ried out using glass plates (40 cm×20 cm or 20 cm×20 cm) coated
with Merck silica gel 60 F254 (1.5–2.0 mm layer thickness). Petro-
leum ether refers to the fraction boiling between 40 °C and 60 °C.
Synthesis of Ketones
The ketones, 3, 4, and 4-methoxybenzophenone were either ob-
tained commercially or synthesized. Ketones 23 and 26 have pre-
viously been synthesized in these laboratories by established meth-
ods.[51,58,59]
Crystal packing is shown in Figure 3. Two crystallo-
graphically distinct π-π interactions stabilise the crystal
structure. One of these involves the cyclohexadienone moi-
ety and its centrosymmetric counterpart (Figure 3, centre),
with centroid-centroid distance 3.643 Å. This interaction is
complemented by a weak intermolecular hydrogen bond in-
volving the carbonyl oxygen atom (C1–H···O22i with C···O
3.451(2) Å and C–H···O angle 152°, i = 1 – x, 1 – y, 1 –
z).The other π-π interaction is between phenyl ring
C1ǞC10 and its c-glide related counterpart (overlapping
rings in Figure 3), with centroid-centroid distance 3.825 Å.
trans-10,11-Dibromo-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-
one (16): 5H-Dibenzo[a,d]cyclohepten-5-one (4, 50 g, 0.242 mol) in
glacial acetic acid (400 mL), was treated with bromine (20 mL) in
acetic acid (250 mL) at ambient temperature. The mixture was left
to stand at room temperature for 15 h, filtered, the precipitate
washed with small quantities of petroleum ether, and dried under
reduced pressure, affording white crystals of 16 (63.8 g, 72%), m.p.
208–209.8 °C (ref.[44] m.p. 210–211 °C). IR (nujol): ν = 1639 cm–1
˜
(s, C=O), 1589, 1577, 1463, 1379, 1337, 1298, 1245, 1185, 1147,
1103, 929. 1H NMR (300 MHz, CDCl3): δ = 5.82 (s, 2 H, H-10, 1-
H), 7.20–8.71 (m, 6 H, Ar-H), 8.12 (d, J = 7.6 Hz, 2 H, 4-H, 6-H).
13C NMR (75 MHz, CDCl3): δ = 53.2 (C-10, C-11), 130.0, 131.4,
131.9, 133.1 (Ar, C-H), 137.1 138.4, 170.4 (quat. Ar), 192.6 (C=O).
EI HRMS (70 eV): 367.90497 (0.83%), 365.90700 (C15H1081Br2O,
1.67 %), 363.91141 (C15H1079Br2O, M+, 0.86 %), 284.99259
(C15H1079BrO, 91.77 %), 206.07329 (C15H11O, 100 %), 178.07859
(C14H10, 82.26%), 176.06326 (25.97%), 89.03928 (C7H5, 28.43%).
C15H1079Br2O: calcd. 363.90984; found 363.91141.
Conclusions
An efficient synthesis for a series of novel p-quinone me-
thides under mild reaction conditions has been devel-
oped.The mechanism of the O-dealkylation reaction has
been discussed in terms of carbocation stability, conforma-
tional and steric effects and the possible formation of a
transient ketal intermediate. Furthermore, the X-ray struc-
ture confirmed the conformation of a model compound,
showing the conformational twisting in the tricyclic system
in order to accommodate the planar cyclohexen-2,5-dien-
one moiety, thus explaining their relative stabilities. This
10-Bromo-5H-dibenzo[a,d]cyclohepten-5-one (17): Dibromide 16
(18.40 g, 0.05 mol) and NaOH (6 g) in methanol (400 mL) were
heated under reflux on a water-bath for 2 h. The hot solution was
filtered, cooled and the precipitate re-crystallized from methanol
to give white crystals of ketone 17 (9.3 g, 65%), m.p. 115.0–116 °C
(ref.[44] m.p. 116 °C). IR (CHCl ): ν = 1653 cm–1 (C=O), 1607,
˜
3
1591, 1445, 1313, 1223, 1159, 1114, 933. 1H NMR (300 MHz,
CDCl3): δ = 7.6–8.1 (m, 9 H, Ar-H and H-11). 13C NMR (75 MHz,
study also sheds more light on the inability of 5- and six- CDCl3): δ = 129.0, 129.4, 130.6, 131.0, 131.4, 131.5, 133.2, 135.3
Eur. J. Org. Chem. 2005, 2607–2619
www.eurjoc.org © 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 2613

B. Taljaard, J. H. Taljaard, C. Imrie, M. R. Caira
FULL PAPER
(Ar, C-H and C-11), 125.0, 133.3, 139.2, 139.7 (quat. Ar and C-
10),194.7 (C=O). EI HRMS (70 eV); m/z: 285.98329 (C15H981BrO,
M + 2, 97.14%), 283.98447 (C15H979BrO, M+, 100%), 257.98702
(C14H981Br, 65.06%), 255.98905 (C14H979Br, 66.41%), 177.07034
(C14H9, 54.11%), 176.06310 (63.32%), 151.05460 (C12H7, 22.19%),
5-(4-Butyloxyphenyl)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-
ol (5b): 1-Bromo(4-butyloxy)benzene (7.43 g, 36.4 mmol) in THF
(100 mL), magnesium (0.81 g, 33.5 mmol) and ketone 3 (4.5 g,
21.6 mmol) yielded a crude residue that upon PLC separation with
CH2Cl2 as mobile phase, afforded pure 5b as a light-yellow gum,
88.03161 (C7H4, 49.27%). C15H979BrO: calcd. 283.98368; found which could not be induced to crystallize (4.95 g, 64 %). IR
283.98447.
(CHCl ): ν = 3604 cm–1 (OH), 3430 (OH), 3007, 1606, 1578, 1505,
˜
3
1481, 1455, 1380, 1294, 1246, 1177, 1110, 1068. 1H NMR
( 3 0 0 M H z , C D C l 3 ) : δ = 0 . 9 8 ( t , J = 7 . 3 H z , 3 H ,
- C H 2 C H 2 C H 2 C H 3 ) , 1 . 4 9 ( s e x t e t , J = 7 . 3 H z , 2 H ,
C H 2 C H 2 C H 2 C H 3 ) , 1 . 7 8 ( q u i n t e t , J = 7 . 9 H z , 2 H ,
CH2CH2CH2CH3), 2.20 (s, 1 H, OH), 2.75 (m, 2 H, CH2–CH2),
2 . 9 4 ( m , 2 H , C H 2 – C H 2 ) , 3 . 9 3 ( t , J = 6 . 5 H z , 2 H ,
-OCH2CH2CH2CH3), 6.76 (d, J = 8.8 Hz, 2 H, Ar-H), 6.95 (d, J
= 8.7 Hz, 2 H, Ar-H), 7.11 (d, J = 7.0 Hz, 2 H, Ar-H), 7.30 (m, 4
H, Ar-H), 8.10 (d, J = 7.4 Hz, 2 H, Ar-H). 13C NMR (75 MHz,
CDCl3): δ = 14.3 (CH3), 19.6 (CH2), 31.4 (OCH3), 31.7 (CH2), 32.9
(CH2), 68.1 (OCH2), 114.8, 126.0, 126.3, 127.9, 128.3, 130.9 (Ar,
CH), 138.2, 141.1, 144.3, 159.0 (quat. Ar). EI HRMS (70 eV); m/z:
358.19429 (C25H26O2, M+, 17.48%), 267.13563 (C18H19O2, 3.31%),
208.08821 (C15H12O, 100 %), 191.08495 (C15H11, 7.48 %),
181.10050 (C14H13, 11.21 %), 177.09146 (C11H13O2, 39.10 %),
165.07122 (C13H9, 7.79 %), 91.05423 (C7H7, 6.36 %). C25H26O2:
calcd. 358.19328; found 358.19429.
1,1-Dichloro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c]cyclo-
hepten-6-one (20): To a stirred solution of 5H-dibenzo[a,d]cy-
clohepten-5-one (4, 6.0 g, 0.029 mol) in benzene (CAUTION)
(100 mL) and petroleum ether (20 mL) at 0–5 °C was added, so-
dium methoxide powder (6.0 g, 0.03 mol), followed by ethyl tri-
chloroacetate (20.0 g, 0.03 mol), dropwise, over 1 h. The suspension
was stirred at 0–5 °C for 5 h, allowed to come to room temperature,
water (20 mL) added, the separated benzene layer washed with
water (3×20 mL), and dried (Na2SO4). Evaporation of the benzene
under reduced pressure, gave an oil which crystallized from ethanol
yielding colourless crystals of the ketone 20 (5.2 g, 60%), m.p. 132–
133.1 °C (ref.[58] m.p. 131–133 °C). IR (CHCl ): ν = 1656 cm–1
˜
3
(C=O), 1597, 1491, 1446, 1293, 1159, 1108, 1050, 943. 1H NMR
(300 MHz, CDCl3): δ = 3.50 (s, 2 H, 1a-H, 10b-H), 7.21–8.60 (m,
6 H, Ar-H), 7.72 (d, J = 6.6 Hz, 2 H, Ar-H). 13C NMR (75 MHz,
CDCl3): δ = 40.3 (C-1a, 10b), 128.7, 130.1, 132.5, 132.6 (Ar, CH),
131.6, 141.1 (quat. Ar), 197.8 (C=O). EI HRMS (70 eV); m/z:
290.00641 (C16H1037Cl2O, 4.80%), 288.01068 (C16H1035Cl2O, M+,
7.37 %), 255.04034 (33.44 %), 253.04361 (C16H1035ClO, 100 %)
225.04728 (C15H1035Cl, 15.70%), 218.07269 (C16H10O, 35.01%),
217.06498 (C16H9O, 13.61 %), 189.07153 (C15H9, 34.52 %),
165.06979 (C13H9, 6.95%), 63.02412 (C5H3, 3.90%). C16H1035Cl2O:
calcd. 288.01087; found 288.01068.
5-(4-Benzyloxyphenyl)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-
ol (5c): 4-(Benzyloxy)-1-bromobenzene (9.48 g, 36.0 mmol) in THF
(100 mL), magnesium (0.91 g, 37.2 mmol) and ketone 3 (5.0 g,
24.0 mmol), gave a crude residue that upon re-crystallization from
benzene/petroleum ether, afforded alcohol 5c (4.85 g, 52%), m.p.
97.0–98.9 °C. IR (CHCl ): ν = 3603 cm–1 (OH), 3406 (OH), 2885,
˜
3
1605, 1582, 1505, 1454, 1380, 1296, 1242, 1177, 1155, 1015, 911.
1H NMR (300 MHz, CDCl3): δ = 2.37 (s, 1 H, OH), 2.75 (m, 2 H,
CH2-CH2), 2.94 (m, 2 H, CH2-CH2), 5.04 (s, 2 H, Ar-CH2-), 6.86
(d, J1 = 2.2 Hz and J2 = 8.9 Hz, 2 H, Ar-H), 6.97 (d, J1 = 2.1 Hz
and J2 = 8.8 Hz, 2 H, Ar-H), 7.13 (d, J = 7.2 Hz, 2 H, Ar-H), 7.22–
7.45 (m, 9 H, Ar-H), 8.12 (dd, J1 = 1.7 Hz and J2 = 7.7 Hz, 2 H,
Ar-H): 13C NMR (75 MHz, CDCl3): δ = 32.9 (C-10, C-11), 70.4
(Ar-CH2-), 115.2, 126.0, 126.3, 127.3, 127.9, 128.0, 128.4, 128.5,
129.0, 131.0 (Ar, CH), 137.2, 138.2, 141.6, 144.2, 158.6 (quat. Ar).
EI HRMS (70 eV); m/z: 392.17683 (C28H24O2, M+, 7.13 %),
211.07657 (C14H11O2, 12.94%), 209.09585 (C15H13O, 30.663%),
208.08952 (C15H12O, 55.20 %), 180.09333 (C14H12, 5.73 %),
165.07044 (C13H9, 5.12%), 131.04964 (C9H7O, 5.22%), 91.05438
(C7H7, 100 %), 77.03800 (C6H5, 2.04 %). C28H24O2: calcd.
392.17636; found 392.17683.
Synthesis of Alcohols
General Procedure: A portion of a solution of 4-bromoanisole
(2.8 g, 0.015 mol) in anhydrous THF (20 mL) was added to a
stirred suspension of magnesium turnings (3.77 g, 0.76 mmol) in
anhydrous THF (100 mL), a crystal of iodine added and the reac-
tion flask warmed to initiate the reaction. The remainder of the 4-
bromoanisole was then added dropwise at a rate as to maintain
gentle refluxing of the solution. After 3 h, a solution of the ketone
(1 mol-equiv.) in anhydrous THF (50 mL), was added slowly and
the reaction mixture heated under reflux for 17 h, cooled, and
poured into a 30% aqueous NH4Cl solution (200 mL). The aque-
ous phase was extracted with CH2Cl2 (3×50 mL), the organic layer
washed with water (3×25 mL), dried (Na2SO4) and the solvent dis-
tilled off. The crude residue was then re-crystallized from benzene/
petroleum ether (CAUTION) affording the pure alcohol.
5-[(4-Chlorobenzyloxy)phenyl]-10,11-dihydro-5H-dibenzo[a,d]cyclo-
hepten-5-ol (5d): 1-Bromo-4-(4-chlorobenzyloxy)benzene (8.57 g,
28.8 mmol) in THF (100 mL), magnesium (0.72 g, 29.8 mmol) and
ketone 3 (4 g, 19.2 mmol) yielded a crude residue that was separated
5-(4-Methoxyphenyl)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-
ol (5a): (4.5 g, 95%), m.p. 126.1–126.9 °C (ref.[62] m.p. 121–123 °C.
IR (CHCl ): ν = 3595 cm–1 (vs), 3403 (br), 3086, 3013, 2834 (s), by PLC (SiO2/CH2Cl2) to give the pure alcohol 5d (3.7 g, 45%), m.p.
˜
3
1602, 1502, 1476, 1456, 1297, 1261, 1178, 1032, 999. 1H NMR 58.1–59.4 °C. IR (CHCl ): ν = 3603 cm–1 (OH), 3418 (OH), 1604,
˜
3
(300 MHz, CDCl3): δ = 2.32 (s, 1 H, OH), 2.60–2.80 (m, 2 H, CH2), 1503, 1375, 1300, 1238, 1177, 1092, 1012, 911. 1H NMR (300 MHz,
2.81–2.98 (m, 2 H, CH2), 3.74 (m, 3 H, OCH3), 6.67 (d, J = 8.9 Hz, CDCl3): δ = 2.34 (s, 1 H, OH), 2.70 (m, 2 H, CH2-CH2), 2.93 (m, 2
2 H, Ar-H), 6.94 (d, J = 8.8 Hz, 2 H, Ar-H), 7.10 (m, 2 H, Ar-H),
7.17–7.31 (m, 4 H, Ar-H), 8.05 (dd, J1 = 7.8, J2 = 2.1 Hz, 2 H, Ar-
H). 13C NMR (75 MHz, CDCl3): δ = 32.8 (CH2CH2), 55.7 (OCH3),
79.3 (C-OH), 114.2, 114.2, 125.0, 125.9, 126.3, 127.9, 128.4, 130.9
(Ar C-H), 138.2, 141.3, 144.2, 159.4 (quat. Ar). EI HRMS (70 eV);
H, CH2-CH2), 5.00 (s, 2 H, Ar-CH2-), 6.82 (d, J = 11.8 Hz, 2 H Ar-
H), 6.95 (d, J = 11.7 Hz, 2 H, Ar-H), 7.11 (d, J = 7.1 Hz, 2 H, Ar-
H), 7.21–7.43 (m, 8 H, Ar-H), 8.11 (dd, J1 = 1.6 Hz and J2 = 7.6 Hz,
2 H, Ar-H). 13C NMR (75 MHz, CDCl3): δ = 32.9 (CH2-CH2), 69.6
(Ar-CH2-), 115.1, 125.9, 126.3, 128.0, 128.5, 129.2, 131.0 (Ar, C-H),
m/z: 316.14660 C22H20O2, M+, 23.52 %), 315.13583 (C22H19O2, 134.2, 135.7, 138.2, 141.8, 144.1, 158.3 (quat. Ar). EI HRMS
3.25 %), 225.09120 (C15H13O2, 10.77 %), 135.04470 (C8H7O2,
86.82 %), 131.04969 (C9H7O, 10.86 %), 108.05733 (C7H8O,
(70 eV); m/z: 428.13331 (C28H2337ClO2, M + 2, 4.37%), 426.13830
(C28H2335ClO2, M+, 11.35%), 408.12823 (C28H2135ClO2, 1.32%),
11.30%), 103.05487 (C8H7, 16.07%), 91.05474 (C7H7, 15.06%), 77 245.03657 (C14H1035ClO2, 5.89%), 209.09394 (25.09%), 208.08920
(C6H5, 18.00%). C22H20O2: calcd. 316.14633; found: 316.14660.
(C15H12O, 86.74 %), 127.01334 (32.07%), 125.01650 (C7H635Cl,
2614
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 2607–2619

The Synthesis of Novel p-Quinone Methides
FULL PAPER
100%), 91.05485 (C7H7, 9.28%), 57.07199 (7.70%). C28H2335ClO2:
calcd. 426.13866; found 426.13830.
3ЈЈ,6ЈЈ-Epoxy-11-(4-methoxyphenyl)-3ЈЈ,6ЈЈ-dihydro-tribenzo[a,c,e]-
cycloheptatrien-11-ol (27): (3.0 g, 80 %) m.p. 165.4–167.5 °C. IR
(CHCl ): ν = 3603 cm–1 (s, OH), 3481 (br., OH), 2838 (s), 1605,
˜
3
5-(4-Methoxyphenyl)-5H-dibenzo[a,d]cyclohepten-5-ol (13): (4.4 g,
1
1508, 1440, 1300, 1251, 1179, 1034. H NMR (300 MHz, CDCl3):
93%), m.p. 136.8–137.9 °C; ref.[58] m.p. 137–139 °C. IR (CHCl ): ν
˜
3
δ = 2.31 (s, 1 H, OH), 3.71 (s, 3 H, OCH3), 5.64 (s, 2 H, 3ЈЈ-H, 6ЈЈ-
H), 6.57 (s, 2 H, 4ЈЈ-H, 5ЈЈ-H), 7.10–7.57 (m, 10 H, Ar-H), 8.30 (d,
J = 7.9 Hz, 2 H, Ar-H). 13C NMR (75 MHz, CDCl3): δ = 55.5
(OCH3), 79.2 (C-11), 85.5 (C-3ЈЈ, C-6ЈЈ), 113.4, 121.7, 126.0, 127.2,
127.9, 128.8 (Ar C-H, C-5, C-6), 131.5, 138.3, 139.7 (quat. Ar),
142.1 (Ar C-H), 148.9, 159.3 (Ar, CH, C-4ЈЈ, C-5ЈЈ). EI HRMS
(70 eV); m/z: 380.14005 (C26H20O3, M+, 100 %), 351.13889
(C25H19O2, 30.57 %), 244.08829 (C18H12O, 20.68 %), 237.09117
(C16H13O2, 25.25 %), 215.08542 (C17H11, 38.65 %), 135.04455
(C8H7O2, 42.67%), 121.06561 (C8H9O, 12.22%). C26H20O3: calcd.
380.14124; found 380.14005.
= 3604 cm–1 (vs), 3391 (br), 3054, 1591, 1460, 1440, 1316, 1165,
1
1112, 1005. H NMR (300 MHz, CDCl3); δ = 2.23 (s, 1 H, OH),
3.69 (s, 3 H, OCH3), 6.49 (s, 4 H, 2×Ar, CH, 10-H,11-H), 6.69 (s,
2 H, Ar-H), 7.25–7.39 (m, 4 H, Ar-H), 7.42–7.52 (m, 2 H, Ar-H),
8.20 (d, J = 8.1 Hz, 2 H, Ar-H). 13C NMR (75 MHz, CDCl3); δ =
55.1 (CH3O), 78.3 (C-OH), 112.8, 124.1, 124.6, 126.5, 126.8, 127.6,
127.9, 128.0, 128.3, 128.6, 129 3, 130.1, 130.8, 131.0, 131.2, 131.5,
(Ar, C-H), 133.2, 133.4, 138.1, 142.6, 158.7 (quat. C-atoms). EI
HRMS (70 eV); m/z: 314.13128 (C22H18O2, M+, 100%), 313.12182
(C22H17O2, 6.88 %),297.12625 (C22H17O, 3.24 %), 207.08123
(C15H11O, 23.64 %), 178.07799 (C14H10, 32.70 %), 165.07037
(C13H9, 3.50%), 152.06262 (C12H8, 5.34%), 135.04466 (C8H7O2,
36.57%), 92.02633 (C6H4O, 6.35%). C22H18O2: calcd. 314.13068;
found 314.13128.
5-(4-Methoxynaphthalen-1-yl)-10,11-dihydro-5H-dibenzo[a,d]cyclo-
hepten-5-ol (7a): 1-Bromo-4-methoxynaphthalene (4.30 g,
19.1 mmol) in THF (100 mL), magnesium (0.72 g, 29.6 mmol) and
5H-dibenzo-10,11-dihydro[a,d]cyclohepten-5-one 3 (2.65 g,
12.74 mmol) gave a sparingly soluble white solid, which, after
washing with benzene and drying, afforded pure 7a (3.2 g, 60%),
1,1-Dichloro-6-(4-methoxyphenyl)-1,1a,6,10b-tetrahydrodibenzo-
[a,e]cyclopropa[c]cyclohepten-6-ol (21): (3.7 g, 92%), m.p. 247.1–
249.1 °C. IR (CHCl ): ν = 3603 cm–1, 3413 (OH), 1605, 1508, 1484,
˜
3
m.p. 209.7–210.8 °C. IR (nujol): ν = 3526 cm–1 (OH), 1619, 1588,
˜
1298, 1250, 1179, 1038, 837. 1H NMR (300 MHz, CDCl3): δ = 2.09
(s, 1 H, OH), 2.59 (s, 2 H, 1a-H, 10b-H), 3.82 (s, 3 H, OCH3), 6.83
(d, J = 6.8 Hz, 2 H, Ar-H), 7.0 (d, J = 6.7 Hz, 2 H, Ar-H), 7.26–
7.40 (m, 6 H, Ar-H), 7.99 (m, 2 H, Ar-H). 13C NMR (75 MHz,
CDCl3): δ = 38.5 (C-1a, C-10b), 55.7 (OCH3), 63.7 (quat., C-1),
114.5, 125.1, 127.9, 128.0, 128.6, 133.3 (CH, Ar), 129.8, 141.0,
146.3, 159.4 (quat. Ar). EI HRMS (70 eV); m/z: 398.06798
(13.14 %), 396.06846 (C23H1835Cl2O2, M+, 22.05 %), 361.10057
(C23H1835ClO2, 40.26%), 325.12290 (C23H17O2, 100%), 297.12693
(C15H1835ClO2, 16.45 %), 290.13172 (C20H18O2, 35.80 %),
265.10012 (C15H1835ClO2, 19.39 %), 253.04036 (C16H1035ClO,
29.79%), 218.07236 (C16H10O, 27.77%), 77.03913 (C6H5, 20.97%).
C23H1835Cl2O2: calcd. 396.06839; found 396.06846.
1514, 1479, 1460, 1389, 1365, 1323, 1274, 1250, 1215, 1157, 1091,
1007, 968. 1H NMR (300 MHz, CDCl3): δ = 2.76 (s, 1 H, OH),
2.62–2.86 (m, 4 H, 10-H, 11-H), 6.65 (d, J = 7.3 Hz, 1 H, Ar-H),
7.02–7.42 (m, 9 H, Ar-H), 8.03 (d, J = 8.7 Hz, 1 H, Ar-H), 8.10
(dd, J1 = 7.9, J2 = 1.3 Hz, 2 H, Ar-H), 8.30 (d, J = 10.6 Hz, 1 H,
Ar-H). 13C NMR (75 MHz, CDCl3): 32.2 (2×CH2), 55.9 (CH3),
80.1 (quat., C-5), 102.6,122.8, 124.9, 125.3, 126.3, 126.58, 126.64
(Ar, C-H), 127.2 (quat. Ar), 127.7, 127.8, 131.0 (Ar, C-H), 131.6,
134.0, 137.2, 146.1, 156.1 (quat. Ar). EI HRMS (70 eV); m/z:
366.16188 (C26H22O2, M+, 21.73%), 348.15093 (C26H20O, 3.94%),
209.09303 (26.64 %), 208.08888 (C15H12O, 100 %), 185.06017
(C12H9O2, 36.43%), 178.07835 (C14H10, 6.13%), 165.07015 (C13H9,
5.68%), 158.07227 (C11H10O, 6.59%), 115.05423 (4.55%), 91.05498
(C7H7, 3.58%). C26H22O2: calcd. 366.16198; found 366.16188.
10-Bromo-5-(4-methoxyphenyl)-5H-dibenzo[a,d]cyclohepten-5-ol
(18): (3.1 g, 76%), m.p. 145.5–146.6 °C. IR (CHCl ): ν = 3606 cm–1
˜
3
5-(3,4-Dimethoxyphenyl)-10,11-dihydro-5H-dibenzo[a,d]cyclohep-
ten-5-ol (7b): 1-Bromo-3,4-dimethoxybenzene (p-bromoveratrole)
(7.82 g, 37.2 mmol) in THF (100 mL), magnesium (0.91 g,
37.2 mmol), and ketone 3 (5.0 g, 24.0 mmol) yielded a crude solid
residue, which crystallized from benzene/petroleum ether affording
white crystals of 7b (5.0 g, 60%), m.p. 189.1–190.2 °C. IR (CHCl3):
(OH), 3387 (OH), 2838, 1608, 1508, 1479, 1439, 1327, 1300, 1249,
1180, 1164, 1118, 1035. H NMR (300 MHz, CDCl3): δ = 2.28 (s,
1
1 H, OH), 3.76 (s, 3 H, OCH3), 6.69 (s, 4 H, Ar-H), 7.20–7.59 (m,
6 H, Ar-H), 7.87 (d, J = 7.5 Hz, 2 H, 11-H), 8.16 (dd, J1 = 4.6 Hz
and J2 = 5.2 Hz, 2 H, Ar-H). 13C NMR (75 MHz, CDCl3): δ =
55.6 (OCH3), 113.7, 124.2, 124.8, 125.2, 127.1, 127.4, 127.9, 128.7,
130.0, 129.98, 134.3 (Ar. CH, C-11), 125.2, 132.5, 133.3, 137.9,
144.3, 144.4, 159.6 (quat. Ar, C-10). EI HRMS (70 eV); m/z:
394.03914 (C22H1781BrO2, M + 2, 0.25 %), 392.03842 (C22
H1779BrO2, M+, 0.25%), 313.12325 (C22H17O2, 100%), 295.11193
(C22H15O, 2.60 %), 269.09456 (C20H13O, 2.79 %), 252.09424
(C20H12, 4.86%), 189.07012 (C15H9, 2.58%), 135.04509 (C8H7O2,
13.83 %), 78.04645 (C6H6, 28.35 %). C22H1779BrO2: calcd.
392.04119; found 392.03842.
ν = 3603 cm–1 (s, OH), 3410 (br., OH), 3010, 2837, 1601, 1509,
˜
1482, 1464, 1410, 1326, 1256, 1138, 1026. 1H NMR (300 MHz,
CDCl3): δ = 2.39 (s, 1 H, OH), 2.74 (m, 2 H, CH2–CH2), 2.94 (m,
2 H, CH2–CH2), 3.63 (s, 3 H, OCH3), 3.85 (s, 3 H, OCH3), 6.55
(d, J = 7.0 Hz, 2 H, Ar-H), 6.72 (d, J = 7.0 Hz, 1 H, Ar-H), 7.03–
7.40 (m, 6 H, Ar-H), 8.10 (dd, J1 = 1.5 Hz and J2 = 7.6 Hz, 2 H,
Ar-H). 13C NMR (75 MHz, CDCl3): δ = 32.9 (C-10, C-11), 56.2
(OCH3), 56.3 (OCH3), 110.3, 111.1, 119.7, 125.9, 126.2, 128.0,
130.9 (Ar, CH), 138.3, 141.8, 144.1, 148.9, 149.3 (quat. Ar). EI
HRMS (70 eV); m/z: 346.15677 (C23H22O3, M+, 63.85 %),
328.14640 (C23H20O2, 8.88 %), 255.10110 (C16H15O3, 5.87 %),
209.09502 (C15H13O, 39.20 %), 208.08912 (C15H12O, 100 %),
191.08552 (C15H11, 9.75 %), 165.05694 (C9H9O3, 54.20 %),
91.05479 (C7H7, 8.36 %). C23H22O3: calcd. 346.15689; found
346.15677.
9-(4-Methoxyphenyl)-9H-tribenzo[a,c,e]cyclohepten-9-ol (24):
(2.65 g, 72%), m.p. 169.6–170.7 °C. IR (CHCl ): ν = 3604 cm–1
˜
3
(OH), 3391 (OH), 2838, 1606, 1582, 1508, 1438, 1298, 1248, 1178,
1124, 1035, 1020. 1H (300 MHz, CDCl3): δ = 2.21 (s, 1 H, OH),
3.62 (s, 3 H, OCH3), 6.40 (d, J = 8.8 Hz, 2 H, Ar-H), 6.71 (d, J =
8.8 Hz, 2 H, Ar-H), 7.00–7.62 (m, 10 H, Ar-H), 8.19 (d, J = 7.8 Hz,
2 H, Ar-H). 13C NMR (75 MHz, CDCl3): δ = 55.5 (OCH3), 113.2,
123.7, 127.4, 127.6, 127.7, 128.5, 129.2, 130.4 (Ar, CH, C-9), 136.7,
5-(4-Methoxy-3,5-dimethylphenyl)-10,11-dihydro-5H-dibenzo[a,d]-
137.6, 139.6, 146.9, 158.8 (quat. Ar). EI HRMS (70 eV); m/z: cyclohepten-5-ol (7c): 4-Bromo-1-methoxy-2,6-dimethylbenzene
364.14597 (C26H20O2, M+, 20.17%), 229.10214 (C18H13, 59.53%),
(4.65 g, 21.6 mmol) in THF (100 mL), magnesium (0.54 g,
228.09491 (C18H12, 52.69%), 135.04493 (C8H7O2, 100%), 77.03919 22.3 mmol) and ketone 3 (3.0 g, 14.4 mmol) yielded a solid, which
(C6H5, 3.61%). C26H20O2: calcd. 364.14633; found 364.14597. crystallized from benzene/petroleum ether as 7c (2.9 g, 59%), m.p.
Eur. J. Org. Chem. 2005, 2607–2619
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2615

B. Taljaard, J. H. Taljaard, C. Imrie, M. R. Caira
FULL PAPER
208.5–210.7 °C. IR (CHCl ): ν = 3603 cm–1 (OH), 3430 (OH),
4-(Dibenzo[a,d]cyclohepten-5-ylidene)cyclohexa-2,5-dienone (14):
˜
3
3010, 1482, 1455, 1318, 1228, 1160, 1132, 1015. 1H NMR (1.74 g, 55 %), m.p. 180.0–181.0 °C (ref.[40] m.p.183–185°C). IR
(300 MHz, CDCl3): δ = 2.16 (s, 6 H, 2×CH3), 2.36 (s, 1 H, OH), (CHCl ): ν = 1633 cm–1 (C=O), 1525, 1433, 1383, 1224, 866. 1H
˜
3
2.74 (m, 2 H, CH2-CH2), 2.97 (m, 2 H, CH2-CH2), 3.70 (s, 3 H, NMR (300 MHz, CDCl3): δ = 6.38 (d, J = 10.2 Hz, 2 H, CH=CH-
OCH3), 6.64 (s, 2 H, Ar-H), 7.08–7.40 (m, 6 H, Ar-H), 8.06 (d, J
= 7.5 Hz, 2, Ar-H). 13C NMR (75 MHz, CDCl3): δ = 16.7
(2 × CH3), 32.8 (CH2–CH2), 79.4 (OCH3), 125.8, 126.2, 127.4,
127.9, 130.9 (CH, Ar), 131.3, 138.1, 144.2, 156.8 (quat. Ar, C-5).
EI HRMS (70 eV); m/z: 344.17852 (C24H24O2, M+, 52.03 %),
326.16828 (C24H22O, 8.21 %), 209.09529 (C15H13O, 45.95 %),
C=O), 7.01 (s, 2 H, 10-H,11-H), 7.30 (d, J = 10.4 Hz, 2 H,
CH=CH-C=O), 7.35–7.5 (m, 8 H, Ar-H). 13C NMR (75 MHz,
CDCl3): δ = 128.5, 128.8, 128.9, 129.6 138.0 (Ar, C-H, CH=CH-
C=O and C-10, C-11), 134.5 136.1 156.8 (quat. Ar), 187.2 (C=O).
EI HRMS (70 eV); m/z: 282.10474 (C21H14O, M+, 100 %),
254.10536 (C20H14, 12.94 %), 253.10136 (C20H13, 52.9 %),
208.08839 (C15H12O, 91.96 %), 191.08528 (C15H11, 10.75 %), 252.09411 (C20H12, 31.84 %), 126.04597 (C10H6, 13.38 %).
180.09344 (C14H12, 24.97 %), 163.07499 (C10H11O2, 100 %),
136.08887 (C9H12O, 16.99 %), 131.04960 (C9H7O, 9.99 %).
C24H24O2: calcd. 344.17763; found 344.17852.
C21H14O: calcd. 282.10447; found 282.10474.]
4-(10-Bromodibenzo[a,d]cyclohepten-5-ylidene)cyclo-
hexa-2,5-dienone (19): (3.29 g, 84 %), m.p. 184.1–188.9 °C. IR
(CHCl ): ν = 1633 cm–1 (C=O), 1561, 1531, 1480, 1431, 1383, 1206,
˜
3
5-(4-Allyloxyphenyl)-5H-dibenzo[a,d]cyclohepten-5-ol (15): 4-(Al-
lyloxy)-1-bromobenzene (4.65 g, 21.8 mmol) in THF (100 mL),
magnesium (0.55 g, 22.6 mmol) and ketone 4 (3.0 g, 14.5 mmol)
gave a crude residue that upon re-crystallization from benzene/pe-
troleum ether, afforded alcohol 15 (2.77 g, 56 %), m.p. 107.0–
1164, 1103, 866. 1H NMR (300 MHz, CDCl3): δ = 6.42 (d, J =
9.9 Hz, 2 H, CH=CH-C=O), 7.20–7.53 (m, 9 H, Ar-H, CH=CH-
C=O), 7.62 (s, 1 H, 11-H), 7.88 (m, 1 H, Ar-H). 13C NMR
(75 MHz, CDCl3): δ = 128.2, 128.6, 128.7, 128.9, 129.0, 129.1,
130.0, 130.1, 130.4, 134.0, 137.6, 137.7 (Ar, CH, C-11, CH=CH-
C=O), 125.0, 129.4, 133.7 137.3, 155.1 (quat. Ar, C-10), 187.22
(C=O). EI HRMS (70 eV); m/z: 362.01341 (C21H1381BrO, M + 2,
99.84 %), 360.01572 (C21H1379BrO, M+, 100 %), 299.10527
108.0 °C. IR (CHCl ): ν = 3602 cm–1 (OH), 3385 (OH), 1606, 1506,
˜
3
1433, 1298, 1239, 1176, 1114, 1018, 917. 1H NMR (300 MHz,
CDCl3): δ = 2.27 (s, 1 H, OH), 4.44 (d, J = 5.4 Hz, 2 H, OCH2),
5.24 (dd, J1 = 1.3 Hz and J2 = 10.5 Hz, 1 H, CH=CH2), 5.39 (dd,
J1 = 1.5 Hz and J2 = 17.3 Hz, 1 H, CH=CH2), 6.0 (octet, J =
5.2 Hz, 1 H, CH=CH2), 6.51–6.65 (m, 4 H, Ar-H), 6.73 (s, 2 H, H-
10, H-11), 7.30–7.58 (m, 6 H, Ar-H), 8.2 (d, J = 7.9 Hz, 2 H, 4-H,
6-H). 13C NMR (75 MHz, CDCl3): δ = (CDCl3) 69.1 (benzyl C),
118.2, 114.8, 125.0, 127.0, 128.4, 128.5, 128.6, 129.1, 131.7, 133.6
(Ar, CH, alkene C), 133.7, 138.7, 143.0, 158.3 (quat. Ar). EI HRMS
(70 eV); m/z: 340.14668 (C24H20O2, M+, 100 %), 300.11476
(C21H16O2, 18.15 %), 299.10853 (C21H15O2, 30.31%), 281.09609
(C21H13O, 14.15 %), 207.08053 (C15H11O, 17.46 %), 179.08450
(C14H11, 17.93 %), 178.07822 (C14H10, 32.12 %), 161.06082
(C10H9O2, 18.97%), 121.02869 (C7H5O2, 7.92%). C24H20O2: calcd.
340.14633; found 340.14668.
(31.51 %), 281.09543 (C21H13O, 35.16 %), 253.10003 (C20H13
45.05 %), 252.09393 (C20H12, 63.14 %), 250.07825 (C20H10
27.23%), 226.07852 (C18H10, 15.44%), 126.04638 (C10H6, 25.98%),
125.03897 (C10H5, 20.28 %), 113.03869 (C9H5, 26.02 %).
C21H1379BrO: calcd. 360.01498; found 360.01572.
,
,
4-(1,1-Dichloro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa-
[c]dibenzo[a,d]cyclohepta-5-ylidene)cyclohexa-2,5-dienone (22):
(1.98 g, 50 %), m.p. 222.5–225.7 °C. IR (CHCl ): ν = 1633 cm–1
˜
3
(C=O), 1579, 1532, 1484, 1446, 1383, 1219, 1175, 1162, 1107, 1041,
1
950. H NMR (300 MHz, CDCl3): δ = 3.35 (s, 2 H, H-1a, H-10b),
6.44 (d, J = 10.1 Hz, 2 H, CH=CH-C=O), 7.16 (d, J = 7.5 Hz, 2
H, Ar-H), 7.24–7.50 (m, 6 H, Ar-H, CH=CH-C=O, 7.53 (d, J =
7.6 Hz, 2 H, Ar-H). 13C NMR (75 MHz, CDCl3): δ = 37.3 (C-1a,
C-10b), 61.8 (C-1), 128.0, 129.3 129.7 129.9 133.3 138.0 (Ar, C-H,
CH=CH-CO), 130.0, 130.4, 140.2, 158.0 (quat. Ar), 187.4 (C=O).
EI HRMS (70 eV); m/z: 366.04129 (68.09%), 365.04626 (23.29%),
364.04268 (C22H14O35Cl2, M+, 100 %), 331.06922 (18.85 %)
329.07252 (C22H1435ClO, 56.32%), 293.09555 (C22H13O, 38.56%),
265.10083 (C21H13, 61.17 %), 263.08625 (C21H11, 29.69 %),
252.093441 (C20H12, 12.53 %), 202.07831 (C16H10, 17.06 %),
113.03716 (C9H5, 4.70%). C22H1435Cl2O: calcd. 364.04217; found
264.04268. C22H14Cl2O (365.26): calcd. C 72.34, H 3.86; found C
72.25, H 3.65.
Synthesis of p-Quinone Methides
The p-methoxyaryl alcohol (10.8 mmol) in dichloromethane
(100 mL) was treated with trifluoroacetic acid (7.5 g, 65.8 mmol)
and water (2.0 g, 110 mmol), the mixture stirred at ambient tem-
perature for 72 h., cooled, and treated with 20% aqueous NaOH
(3×50 mL). The organic layer was separated, washed with water
(3×30 mL), dried (Na2SO4), the solvent distilled off and the crude
residue further purified by PLC (SiO2/CH2Cl2). Re-crystallization
of the solid, obtained from by elution of a bright yellow band from
the PLC plates, from ethanol, afforded yellow crystals of the corre-
sponding p-quinone methide.
4-(Tribenzo[a,c,e]cyclohepten-9-ylidene)cyclohexa-2,5-dienone (25):
(0.83 g, 23 %), m.p. 264.4–265.5 °C. IR (CHCl ): ν = 1632 cm–1
˜
3
4-(10,11-Dihydro-dibenzo[a,d]cyclohepten-5-ylidene)cyclohexa-2,5-di-
(C=O), 1579, 1559, 1537, 1471, 1431, 1384, 1273, 1226, 1162, 866.
1H NMR (300 MHz, CDCl3): δ = 6.38 (d, J = 10.1 Hz, 2 H,
CH=CH-C=O), 7.28–7.35 (m, 2 H, Ar-H), 7.40–7.55 (m, 8 H, Ar-
H, CH=CH-C=O), 7.60–7.74 (m, 4 H, Ar-H). 13C NMR (75 MHz,
CDCl3): δ = 127.8, 127.9, 128.5 129.4 129.7, 130.1, 130.5 138.0 (Ar,
CH, CH=CH-C=O), 137.5, 137.9, 140.8, 157.9 (quat. Ar), 187.4
(C=O). EI HRMS (70 eV); m/z: 332.12052 (C25H16O, M+, 100%),
303.11607 (C24H15, 32.10 %), 302.10970 (C24H14, 22.74 %),
300.09353 (C24H12, 10.93 %), 276.09466 (C22H12, 11.25 %),
150.04618 (C12H6, 8.72%), 138.04649 (C11H6, 7.55%). C25H16O:
calcd. 332.12012; found 332.12052.
enone (6): (2.81 g, 91%), m.p. 158.0–159.7 °C. IR (CHCl ): ν =
˜
3
1632 cm–1 (C=O), 1524, 1478, 1233, 1160, 866. 1H NMR
(300 MHz, CDCl3): δ = 3.35 (dd, J1 = 7.1 Hz and J2 = 11.9 Hz, 2
H, CH2CH2), 2.95 (dd, J1 = 7.1 Hz and J2 = 11.8 Hz, 2 H,
CH2CH2), 6.42 (d, J = 10.1 Hz, 2 H, CH=CH-C=O), 7.1–7.4 (m,
8 H, Ar-H), 7.49 (d, J = 10.1 Hz, 2 H, CH=CH-C=O). 13C NMR
(75 MHz, CDCl3): δ = 32.7 (CH2), 32.8 (CH2), 115.9, 121.6, 126.0,
126.2, 127.8, 128.4, 129.3, 129.5, 129.6, 130.3, 130.9, 138.5 (Ar, CH,
CH=CH-C=O and C-10, C-11), 138.2, 140.5, 144.5, 156.7, 161.5
(quat. Ar), 187.59 (C=O). EI HRMS (70 eV): m/z: 284.11995
(C21H16O, M+, 73.24 %), 239.08345 (C19H11, 18.24%), 215.0860
(C17H11, 8.80%), 191.08549 (C15H11, 32.64%), 178.0774 (C14H19,
4-(10,11-Dihydrodibenzo[a,d]cyclohepten-5-ylidene)-4H-naphthalen-
8.50 %), 50.94805 (100 %). C21H16O: calcd. 284.12012; found 1-one (8a): (3.3 g, 91%), m.p. 172.9–173.9 °C. IR (CHCl ): ν =
˜
3
284.11995.
1645 cm–1 (C=O), 1598, 1543, 1481, 1453, 1402, 1301, 1238, 1215,
2616
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 2607–2619

The Synthesis of Novel p-Quinone Methides
FULL PAPER
1178, 1156, 1129, 1096, 1027. 1H NMR (300 MHz, CDCl3): δ =
(s, 3 H, p-CH3O), 6.94 (d, J = 8.3 Hz, 2 H, Ar-H), 7.32 (d, J =
3.00 (m, 2 H, CH2–CH2), 3.54 (m, 2 H, CH2–CH2), 6.50 (d, J = 8.5 Hz, 2 H, Ar-H), 7.41 (s, 10 H, Ar-H). 13C NMR (50 MHz,
10.3 Hz, 1 H, CH=CH-C=O), 6.97 (d, J = 7.4 Hz, 1 H), 7.05–7.45
(m, 10 H, Ar-H), 7.74 (d, J = 10.3 Hz, 1 H, CH=CH-C=O), 8.26 131.5 (Ar, C-H), 141.5 (quat. Ar), 149.4 (quat. Ar), 160.8 (C=O).
(d, J = 7.7 Hz, 1 H, Ar-H). 13C NMR (75 MHz, CDCl3): δ = 32.9 EI LRMS: m/z; 290 (M+, 37.21%), 274 (12.01%), 273 (12.64%),
(CH2–CH2), 32.0 (CH2–CH2), 126.1, 126.8, 126.9, 127.2, 128.2, 214 (18.94 %), 213 (100.00 %), 185 (10.88 %), 135 (28.36 %), 105
128.4, 128.9, 129.1, 129.3, 129.4, 129.8, 130.6, 131.0, 136.8 137.9, (56.97 %), 77 (46.76 %). EI HRMS (70 eV): C20H18O2: calcd.
CDCl3): δ = 57.4 (p-CH3O), 83.9 (COH), 115.4, 129.3, 130.0, 130.1,
142.5 (Ar, C-H, CH=CH-C=O), 127.6, 141.2 154.3 (quat. Ar), 290.1307; found 290.1306.
185.9 (C=O). EI HRMS (70 eV); m/z: 334.13540 (C25H18O, M+,
(4-Methoxyphenyl)naphthalen-1-ylphenylmethanol (11b): 1-Bromo-
100%), 303.11571 (C24H15, 6.03%), 291.11611 (C23H15, 8.88%),
289.10206 (C23H13, 15.36 %), 191.08568 (C15H11, 29.57 %),
145.05347 (8.93 %), 138.04589 (C11H6, 7.91 %). C25H18O: calcd.
334.13577; found 334.13540.
naphthalene (4.33 g, 20.9 mmol) in anhydrous THF (100 mL),
magnesium (0.53 g, 21.9 mmol) and 4-methoxybenzophenone
(3.0 g, 14.1 mmol), afforded pure 11b (2.69 g, 56%) as a light brown
gum which could not be induced to crystallize. IR (CHCl ): ν =
˜
3
3597 cm–1 (OH), 3415 (OH), 2838, 1607, 1582, 1509, 1395, 1297,
4-(10,11-Dihydrodibenzo[a,d]cyclohepten-5-ylidene)cyclohexa-2-meth-
oxy-2,5-dienone (8b): (1.91 g, 56 %), m.p. 211.1–212.5 °C. IR
1
1179. H NMR (300 MHz, CDCl3): δ = 3.50 (s, 1 H, OH), 3.85 (s,
3 H, OCH3), 6.80–8.35 (m, 16 H, Ar-H). 13C NMR (75 MHz,
CDCl3): δ = 55.7 (OCH3), 83.5 (C-OH), 113.8, 124.7, 125.8, 126.0,
127.6, 128.2, 128.5, 128.6, 128.7, 129.3, 129.5, 129.8 (Ar C-H),
131.9, 135.4, 130.8, 142.8, 147.7, 159.0 (quat. Ar). EI HRMS
(70 eV); m/z: 340.14547 (C24H20O2, M+, 43.17 %), 323.14366
(C24H19O, 32.65 %), 263.10792 (C18H15O2, 49.69 %), 232.0878
(C17H12O, 100 %), 213.09192 (C14H13O2, 68.13 %), 135.04488
(C8H7O2, 63.13%), 105.03417 (C7H5O, 54.27%). C24H20O2: calcd.
340.14633; found 340.14547. In a duplicate synthesis, compound
11b was obtained as white crystals in 62% yield, m.p. 131–133 °C.
This failure of the alcohol to crystallize may be explained in terms
of enclathration of the solvent THF by the host alcohol in the
procedure reported above.[49]
(CHCl ): ν = 1626 cm–1 (C=O), 1570, 1528, 1479, 1453, 1425, 1369,
˜
3
1
1251, 1224, 1203, 1130, 1093, 1013. H NMR (300 MHz, CDCl3):
δ = 2.94 (m, 2 H, CH2–CH2), 3.38 (m, 2 H, CH2–CH2), 3.67 (s, 3
H, OCH3), 6.49 (d, J = 9.9 Hz, 1 H, CH=CH-C=O), 6.66 (d, J =
2.3 Hz, 1 H, CH=CH-C=O), 7.14–7.37 (m, 8 H, Ar-H), 7.45 (dd,
J1 = 2.4 Hz and J2 = 9.9 Hz, 1 H, CH=CH-C=O). 13C NMR
(75 MHz, CDCl3): δ = 32.7 (CH2–CH2), 32.8 (CH2–CH2), 55.5
(OCH3), 109.2, 126.0, 128.5, 129.1, 129.3, 129.3, 129.9, 130.1,
130.4, 137.8 (Ar, CH, CH=CH-C=O), 129.5, 138.5, 138.62, 139.0,
139.1, 153.1, 157.8 (quat. Ar, CH=CH(OCH3)-C=O), 181.49
(C=O). EI HRMS (70 eV); m/z: 314.13075 (C22H18O2, M+, 100%),
296.11856 (C22H16O, 4.90 %), 283.11210 (C21H15O, 7.33 %),
239.08481 (C19H11, 14.61 %), 215.08521 (C17H11, 10.67 %),
191.08568 (C15H11, 47.60%), 113.03875 (C9H5, 7.38%), 91.05501
(C7H7, 5.89%). C22H18O2: calcd. 314.13068; found 314.13075.
(4-Methoxyphenyl)phenyl(2,4,6-trimethylphenyl)methanol (11c): 1-
Bromo-2,4,6-trimethylbenzene (Bromomesitylene) (6.97 g,
35.0 mmol) in THF (100 mL), magnesium (0.90 g, 36.8 mmol) and
4-methoxybenzophenone (5.0 g, 23.6 mmol) afforded 11c (7.05 g,
99 %) as a chromatographically homogeneous yellow gum. IR
4-(10,11-Dihydrodibenzo[a,d]cyclohepten-5-ylidene)cyclohexa-2,6-di-
methyl-2,5-dienone (8c): (2.43 g, 72 %), m.p. 210.4–212.2 °C. IR
(CHCl ): ν = 1637 cm–1 (C=O), 1608, 1532, 1479, 1446, 1428, 1375,
˜
3
(CHCl ): ν = 3598 cm–1 (OH), 3004, 2837, 1607, 1508, 1446, 1295.
1
˜
1340, 1221, 1093, 1029, 916. H NMR (300 MHz, CDCl3): δ = 2.0
3
1H NMR (300 MHz, CDCl3): δ = 1.91 (s, 6 H, 2×CH3), 2.31 (s, 3
H, p-CH3), 2.77 (s, 1 H, OH), 3.84 (s, 3 H, OCH3), 6.87 (d, J =
9.6 Hz, 4 H, Ar-H), 7.16 (s, 1 H, Ar-H), 7.19 (s, 1 H, Ar-H), 7.24–
7.45 (m, 5 H, Ar-H). 13C NMR (75 MHz, CDCl3): δ = 21.0, 21.6,
24.7 (3 × CH3), 55.7 (OCH3), 83.7 (quat. C-OH), 113.8, 127.3,
127.6, 128.2, 128.5, 128.9, 129.2, 129.5, 130.4, 131.7 (Ar, CH),
136.6, 138.1, 138.5, 140.4, 141.8, 148.3, 159.2 (quat. Ar). EI HRMS
(70 eV); m/z: 332.17764 (C23H24O2, M+, 32.62 %), 315.17417
(C23H23O, 20.39 %), 300.15146 (C22H20O, 15.89 %), 255.13822
(C17H19O2, 34.59 %), 213.09120 (C14H13O2, 100 %), 149.09616
(C10H13O, 38.40 %), 147.08066 (C10H11O, 63.82 %), 105.03397
(C5H7O, 43.15 %), 77.03912 (C6H5, 32.95 %). C23H24O2: calcd.
332.17763; found 332.17764.
(s, 6 H, CH3), 2.91 (m, 2 H, CH2-CH2), 3.35 (m, 2 H, CH2-CH2),
7.15–7.37 (m, 10, Ar-H, CH=CH-C=O). 13C NMR (75 MHz,
CDCl3): δ = 17.2 (2×CH3), 32.7 (CH2-CH2), 126.0, 129.1, 129.7,
130.1, 134.4 [Ar, CH, CH=C(OCH3)-C=O], 129.1, 136.4, 138.4,
139.2, 156.7 [quat. Ar, CH=C(OCH3)-C=O], 187.8 (C=O). EI
HRMS (70 eV); m/z: 312.15200 (C23H20O, M+, 100%), 297.12657
(C22H17O, 37.91 %), 269.13110 (C21H17, 10.26 %), 253.10108
(C20H13, 10.64%), 191.08531 (C15H11, 17.43%), 126.04689 (C10H6),
91.05490 (C7H7, 2.20 %). C23H20O: calcd. 312.15142; found
312.15200.
O-Dealkylation of Alcohols Substituted with Various p-Substituents
on the Pendant 5-Phenyl Ring (Schemes 2 and 7)
5-(4-Butyloxyphenyl)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-
5-ol (5b), demethylated according to the general method, gave dien-
one 6 (1.52 g, 51%).
Synthesis of Trityl p-Quinone Methides (Fuchsones)
4-Benzhydrylidenecyclohexa-2,5-diene (12a) was obtained as yellow
1
crystals, 56%, had identical m.p., IR and H NMR spectra as re-
5-(4-Benzyloxyphenyl)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-
5-ol (5c), gave 6 (1.72 g, 56%).
ported.[63] In addition, it had the following mass spectroscopic
data. EI LRMS: m/z; 258 (M+, 100.00 %), 229 (49.76 %), 228
(25.72%), 215 (20.31%), 202 (14.54%), 181 (6.20%), 165 (6.29%),
152 (11.03 %), 101 (12.38 %), 77 (4.70 %).– EI HRMS (70 eV):
C19H14O: calcd. 258.1045; found 258.1049.
5-[(4-Chlorobenzyloxy)phenyl]-10,11-dihydro-5H-dibenzo[a,d]cy-
clohepten-5-ol (5d), gave 6 (1.54 g, 50%).
5-(4-Allyloxyphenyl)-5H-dibenzo[a,d]cyclohepten-5-ol (15), gave 14
(1.7 g, 56%).
4-[Naphthalen-1-yl(phenyl)methylene]cyclohexa-2,5-dienone (12b):
Yield 2.08 g, 62%, m.p. 169.0–170.0 °C. IR (CHCl ): ν = 1628 cm–1
˜
3
Synthesis of Trityl Alcohols
(C=O), 1512, 1443, 1381, 1174, 866. 1H NMR (300 MHz, CDCl3):
δ = 6.31 (d, J = 9.9 Hz, 1 H, CH=CH-C=O), 6.55 (d, J = 10.3 Hz,
1 H, CH=CH-C=O), 7.00 (d, J = 9.9 Hz, 1 H, CH=CH-C=O),
(4-Methoxyphenyl)diphenylmethanol (11a): Alcohol 11a had pre-
viously synthesized in these laboratories in 81% yield,[49] m.p. 54–
56 °C. IR (CHCl ): ν = 3597 cm–1 (OH, s), 3458 (OH, br), 1609, 6.82–8.10 (m, 13 H, Ar-H and CH=CH-C=O). 13C NMR
˜
3
1585. 1H NMR (200 MHz, CDCl3): δ = 3.37 (s, 1 H, br, OH), 3.85 (75 MHz, CDCl3): δ = 125.4, 126.3, 126.8, 127.5, 128.9, 130.5,
Eur. J. Org. Chem. 2005, 2607–2619
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2617

B. Taljaard, J. H. Taljaard, C. Imrie, M. R. Caira
FULL PAPER
130.4, 131.6, 139.0, 139.9 (Ar, CH), 129.66, 132.4, 134.1, 137.9,
X-ray Crystallography: Crystallographic data for 14 are listed in
140.1, 159.3 (quat. Ar, CH=CH-C=O), 187.7 (C=O). EI HRMS Table 1. Intensity data were collected from a yellow, prismatic spec-
(70 eV); m/z: 308.12046 (C23H16O, M+, 100%) 280.12195 (C22H16, imen mounted on a Nonius Kappa CCD diffractometer using Mo-
13.37 %), 279.11693 (C22H15, 36.10 %), 277.10041 (C22H16
13.37 %), 276.09346 (C22H12, 16.0 %), 231.08096 (C17H11O,
17.09%). C23H16O: calcd. 308.12012; found 308.12046.
,
Kα radiation (λ = 0.71069 Å) with the crystal cooled in a stream
of N2 from a Cryostream cooler (Oxford Cryosystems, UK). The
data-collection strategy indicated by the program COLLECT[64] in-
volved suitable combinations of 1° φ- and ω-scans. Program
DENZO-SMN[65] was used for cell refinement and data reduction.
The structure was solved using program SHELXS86[66] and refined
on F2 with SHELXL97[67] with all non-hydrogens modelled anis-
tropically. All H atoms were located in difference electron-density
maps and were included in idealized positions in a riding model
with isotropic thermal parameters equal to 1.2 times those of their
4-[Phenyl(2,4,6-trimethylphenyl)methylene]cyclohexa-2,5-dienone
(12c): Yield 1.93 g, 56%, m.p. 122.5–124.7 °C. IR (CHCl ): ν =
˜
3
1628 cm–1 (C=O), 1607, 1511, 1443, 1379, 1222, 1168. 1H NMR
(300 MHz, CDCl3): δ = 1.60 (s, 3 H, CH3), 2.02 (s, 3 H, CH3), 2.38
(s, 3 H, CH3), 6.38 (dd, J1 = 2.5 Hz and J2 = 10.5 Hz, 1 H,
CH=CH-C=O), 6.43 (dd, J1 = 2.5 Hz and J2 = 10.6 Hz, 1 H,
CH=CH-C=O), 6.95 (m, 3 H), 7.23–7.44 (m, 5 H, Ar-H, CH=CH-
C=O), 7.80 (dd, J1 = 2.5 Hz and J2 = 10.6 Hz, 1 H, CH=CH-
C=O). 13C NMR (75 MHz, CDCl3): δ = 20.8 (CH3), 21.5
(2×CH3), 128.8, 129.1, 129.4, 129.5, 130.4, 131.7, 138.6, 139.1 (Ar,
C-H, CH=CH-C=O), 130.8, 136.4, 136.8, 138.5, 139.0, 160.1 (quat.
Ar), 187.7 (C=O). EI HRMS (70 eV): m/z; 300.15235 (C22H20O,
parent atoms. In the final cycles of refinement, least-squares
weights of the form w = 1/[σ2(Fo)2 + (aP)2 + bP], P = [max.(Fo
,
2
2
0) + 2Fc ]/3 were employed. Molecular parameters were calculated
with PLATON[68] and program ZORTEP[69] was used for illustra-
tions.
M+, 100 %), 285.12743 (C21H17O, 8.70 %), 257.13253 (C20H17
13.48%), 242.10970 (C19H14, 12.19%), 229.10072 (C18H13, 3.78%),
215.08573 (C17H11, 5.40%), 179.08496 (C14H11, 4.73%), 165.07029
(C13H9, 4.86%). C22H20O: calcd. 300.15142; found 300.15235.
,
Table 1. Crystal data, data collection and refinement parameters
for 14.
Parameter
Value
Molecular formula
Molecular mass
Crystal size (mm)
Crystal system
Space group
Temperature
a [Å]
b [Å]
c [Å]
α [°]
β [°]
C21H14O
282.32
0.40×0.30×0.25
monoclinic
P21/c
Synthesis of 5-(4-Methoxyphenyl)-10,11-dihydro-5H-dibenzo[a,d]cy-
clohept-5-ylium Perchlorate (9): 5-(4-Methoxyphenyl)-10,11-dihy-
dro-5H-dibenzo[a,d]cyclohepten-5-ol (5a, 1.0 g, 3.2 mmol) in acetic
anhydride (50 mL) was cooled and 70 % perchloric acid added
dropwise until no further precipitation occurred.[56] The brown pre-
cipitate was filtered, washed with anhydrous ether and dried under
reduced pressure. Re-crystallization from nitromethane/ether/petro-
leum ether gave the dark-yellow perchlorate salt 9 (1.1 g, 83%). IR
173(2)
15.5662(3)
12.6808(2)
7.4708(1)
90
102.921(1)
90
1437.34(4)
4
1.305
592
0.079
1.27–27.48
8887/3306
0.018
(CHCl ): ν = 3017 cm–1, 1611, 1393, 1326, 1208 (s), 1107, 777 (vs),
˜
3
1
744 (vs), 670 (vs). H NMR (300 MHz, CDCl3): δ = 3.24 (s, 4 H,
γ [°]
CH2CH2), 4.44 (s, 3 H, OCH3), 7.30 (d, J = 8.5 Hz, 2 H, Ar-H, 3Ј-
H, 5Ј-H), 7.38–7.62 (m, 8 H, Ar-H), 8.41 (d, J = 8.4 Hz, Ar-H, 4-
H, 6-H). 13C NMR (75 MHz, CDCl3): δ = 33.4 (CH2), 60.8
(OCH3), 121.2, 127.0, 131.1, 132.5 (Ar, C-H), 133.0 (quat. Ar),
133.9 (Ar, C-H), 138.1, 140.0 (quat. Ar), 149.5 (Ar, C-H), 181.8,
201.2 (quat. Ar). The salt 9 was used immediately in the demeth-
oxylation step.
V [Å3]
Z
Dc [g cm–3]
F(000)
μ [mm–1]
2θ range [°]
Reflections collected/unique
Rint
Data completeness [%]
Max./min. transmission
Data/restraints/parameters
Goodnessof-fit (S)
R [F, I Ͼ 2σ(I)]
wR [F2, all]
Δρmax., Δρmin. [e·Å–3]
99.6
Reduction of 5-(4-Methoxyphenyl)-10,11-dihydro-5H-dibenzo[a,d]-
cyclohepten-5-ol (5a)
0.9816/0.9692
3306/0/199
1.04
0.0374
0.0994
5-(4-Methoxyphenyl)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene
(10): 5-(4-Methoxyphenyl)-10,11-dihydro-5H-dibenzo[a,d]cy-
clohepten-5-ol (5a, 5.0 g, 15.8 mmol) in 98% formic acid (100 mL)
was treated with potassium carbonate (1.0 g), and the reaction mix-
ture heated under reflux for 5 h and then cooled in ice. The precipi-
tate was filtered, washed with cold water and re-crystallized from
ethanol yielding 10 (2.47 g, 52 %) as a white solid, m.p. 99.8–
0.18/–0.19
CCDC-186121 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
100.9 °C. IR (CHCl ): ν = 3014 cm–1, 1607, 1507, 1457, 1291, 1245,
˜
3
1
1180, 1109, 1036, 853. H NMR (300 MHz, CDCl3): δ = 2.75 (m,
2 H, CH2-CH2), 3.12 (m, 2 H, CH2-CH2), 3.77 (s, 3 H, OCH3),
5.19 (s, 1 H, H-5), 6.70 (m, 4 H, Ar-H), 7.10–7.42 (m, 8 H, Ar-H).
13C NMR (75 MHz, CDCl3): δ = 32.6 (CH2-CH2), 57.6 (C-5), 58.0
(OCH3), 113.0, 113.7, 126.5, 127.1, 127.6, 128.5, 128.6, 128.9,
130.3, 130.8, 131.2, 131.8 (Ar CH), 135.1, 138.1, 140.3, 140.9,
141.0, 158.0 (quat. Ar). EI HRMS (70 eV): m/z: 300.15136
(C22H20O, M+, 50.07%), 298.13729 (C22H18O, 43.34%), 267.11657
(C21H15, 5.75%), 253.09925 (C20H13, 5.39%), 223.11145 (C16H15O,
Supporting Information (see also the footnote on the first page of
this article): Space-filling and stick models showing the packing in
the crystal structure structure of 14.
Acknowledgments
15.42%), 193.09802 (C15H13, 48.01%), 192.09398 (C15H12, 100%), The authors thank the South African National Research Founda-
165.07014 (C13H9, 11.33 %), 77.03773 (C6H5, 3.14%). C22H20O: tion and the Universities of Port Elizabeth and Cape Town for
calcd. 300.15142; found 300.15136.
financial support and a bursary (J.H.T.). Thanks are also expressed
2618
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 2607–2619

The Synthesis of Novel p-Quinone Methides
FULL PAPER
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Eur. J. Org. Chem. 2005, 2607–2619
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2619