Electroorganic reactions. Part 56: Anodic oxidation of 2-methyl- and 2-benzylnaphthalenes: Factors influencing competing pathways

Article abstract of DOI:10.1016/S0040-4020(02)00495-7

A systematic investigation of the anodic oxidation in nucleophilic media of 2-methyl and 2-benzylnaphthalenes, substituted at the 6-position in the naphthalene nucleus and at the 4-phenyl position of the benzylic side chain, has been carried out to identify factors favouring side-chain substitution. Cyclic voltammetry confirms that 6-substitution has a profound effect on the oxidation potentials of the naphthalene nucleus and ¹³C chemical shifts indicate polar effects at the benzylic carbon. However, little side-chain anodic oxidation is observed under any conditions tried; the radical-cations of electron-rich substrates preferentially dimerise and a strongly electron-withdrawing substituent at the 6-position (EtOSO₂) promotes nuclear substitution. In contrast, oxidation with DDQ in aqueous acetic acid gives efficient side-chain oxidation for electron rich substrates, consistent with hydride transfer, possibly intramolecularly via a charge transfer complex.

Full text of DOI:10.1016/S0040-4020(02)00495-7

TETRAHEDRON
Pergamon
Tetrahedron 58 02002) 5251±5265
Electroorganic reactions. Part 56: Anodic oxidation of
2-methyl- and 2-benzylnaphthalenes: factors in¯uencing
competing pathwaysq
James H. P. Utleyp and Gregor G. Rozenberg
Department of Chemistry, Queen Mary ꢀUniversity of London), Mile End Road, London E1 4NS, UK
Received 8 March 2002; revised 19April 2002; accepted 9May 2002
AbstractÐA systematic investigation of the anodic oxidation in nucleophilic media of 2-methyl and 2-benzylnaphthalenes, substituted at
the 6-position in the naphthalene nucleus and at the 4-phenyl position of the benzylic side chain, has been carried out to identify factors
favouring side-chain substitution. Cyclic voltammetry con®rms that 6-substitution has a profound effect on the oxidation potentials of the
naphthalene nucleus and 13C chemical shifts indicate polar effects at the benzylic carbon. However, little side-chain anodic oxidation is
observed under any conditions tried; the radical±cations of electron-rich substrates preferentially dimerise and a strongly electron-with-
drawing substituent at the 6-position 0EtOSO2) promotes nuclear substitution. In contrast, oxidation with DDQ in aqueous acetic acid gives
ef®cient side-chain oxidation for electron rich substrates, consistent with hydride transfer, possibly intramolecularly via a charge transfer
complex. q 2002 Elsevier Science Ltd. All rights reserved.
The anodic oxidation of alkylaromatics gives nuclear and
side-chain substitution in nucleophilic solvents and dimer-
isation and other combination reactions in non-nucleophilic
media.1±3 Oxidation of toluene 01a) in acetic acid4 gives
predominantly o- and p-acetoxytoluene together with side-
chain acetoxylation. In methanol side-chain substitution
may result in the formation of the corresponding acetals
as precursors to the aldehydes. Nuclear substitution in
methanol often leads to further, ipso, substitution eventually
to give quinone ketals.5,6 In contrast, mesitylene is oxidised
anodically in CH2Cl2±Bu4NBF4 00.1 M) electrolyte to give
a dimer.1 The side-chain oxidation process is synthetically
important and has been developed into at least one industrial
process, a recent example7 being the conversion of 4-t-
butyltoluene into 4-t-butylbenzaldehyde as the anodic
component of a `paired electrosynthesis'.
to be more problematic because of the greater opportunity
for nuclear substitution in the electron-rich arene ring and of
dimerisation, known to occur in electron-rich arenes.1
We report here a systematic exploration of the anodic oxida-
tion of derivatives of 2-methylnaphthalene 02) with a view
to identifying structural features or reaction conditions that
in¯uence the competition between nuclear substitution,
dimerisation and side-chain oxidation. The pattern of substi-
tution in the starting materials is designed to in¯uence both
the electron demand in the arene ring and the acidity of the
2-methylene protons. It is known that the benzylic hydro-
gens are very acidic in radical±cations 0toluene has pKa ca.
40, whereas the corresponding radical±cation has pKa 11)8
but the thermodynamic acidity may not be directly re¯ected
in the kinetic acidity and deprotonation may still be outrun
by competing nuclear substitution and by dimerisation.
Systematic variation of substituents Y in compounds 2
should in principle considerably in¯uence the electron
demand and hence acidity of the 2-methylene protons in
the radical±cations.
The side-chain oxidation of toluene derivatives may be
made quite selective. By analogy, derivatives of naph-
thalene-2-carboxaldehyde are likely to be good starting
materials for the elaboration of functionality at the
2-position to give analogues of compounds with useful
biological activity, including non-steroidal anti-in¯am-
matory compounds. However, the conversion of 2-methyl-
naphthalenes, into naphthalene-2-carboxaldehydes is likely
1. Results and discussion
1.1. Anodic oxidation of toluene derivatives
q For part 55, see Ref. 40.
Optimum conditions were sought for the direct anodic side-
chain oxidation of the 2-methylnaphthalenes by studying
the analogous conversion of toluene derivatives. In the
event no improvement was found on the conditions
Keywords: electrochemical oxidation; alkylnaphthalenes; radical±cations.
Corresponding author. Tel.: 144-20-7882-5023; fax: 144-20-7882-
7794; e-mail: j.utley@qmul.ac.uk
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020002)00495-7

5252
J. H. P. Utley, G. G. Rozenberg / Tetrahedron 58 ꢀ2002) 5251±5265
Table 1. Constant current electrolysis of toluene derivatives in methanol
ratios of [516]/[718] it is inferred that methoxyl 0ratio
81/6ˆ13.7) is more effective than methyl 0ratio 84/14ˆ6)
in promoting side-chain substitution.
Starting compound E0 0V vs. SCE)a
Products 0%)
1a
1b
1c
2.35
2.06
Complex mixtureb
5b 072) 6b 012) [7b18b] 014)
1.2. Anodic oxidation of naphthalene derivatives 2a, 2d,
2e
01.68)c
5c 081)
[7cˆ8c] 06)
Pt electrodes, undivided cell, MeOH±KF 00.15 M), 64 mA cm22, 4.2 F.
CF3CO2H±0CF3CO)2O 07% v/v)±Bu4NClO4 00.1 M).
a
Essentially using the BASF conditions, the more successful
preparative results for the anodic oxidation of the 2-methyl-
6-substituted-naphthalenes are summarised in Table 2.
b
1H NMR shows no evidence of side-chain substitution.
E1/2, CH3CN±Et4NClO4 00.1 M); Ref. 12.
c
The reactions were not clean but according to 1H NMR only
a trace amount of side-chain substituted product was formed
0from 2a). It is clear that dimer formation 09a and 9b) is
preferred for the electron rich compounds, and that the
6-methoxyl substituent greatly enhances dimerisation. In
contrast the strongly electron-withdrawing substituent
EtOSO2 suppresses dimerisation and encourages nuclear
substitution, to give 10. The characterisation of the products
of these electrolyses is described in Section 2.
established by the BASF group9±11 although for con-
venience platinum anodes were used, rather than carbon,
for the relatively small-scale reactions described here. The
formulae of the starting materials 01) and products 04±8) are
listed and the results of preliminary electrolyses are given in
Table 1.
1.3. Oxidation potentials and 13C NMR chemical shifts
The BASF conditions are probably optimal for side-chain
substitution but toluene is not amenable to useful conversion
under these conditions. Electron donating substituents at the
para position enhance side-chain substitution. From the
In the toluene cases electron donation into the ring
encourages side-chain substitution over nuclear substitu-
tion, whereas in the 2-methylnaphthalenes electron-with-
drawal encourages nuclear substitution, which is
Table 2. Constant current electrolysis of 2-methylnaphthalene derivatives in methanol
6-Substituent
0compound)
Concentration
0M)
Solvent
Supporting
electrolyte
Current density
0mA cm22
F
Conversiona
0%)
Side-chainb
0%)
Dimersc 0%)
)
H 02a)
H 02a)
H 02a)
MeO 02d)
MeO 02d)
EtO´SO2 02e)
EtO´SO2 02e)
0.60
0.55
0.14
0.09MeOH
0.13
0.06
MeOH
MeOH
MeOH/CH2Cl2
KF
MeOH/CH2Cl2
MeOH
MeOH/CH2Cl2
KF
KF
H2SO4
64
48
10
4.3
5.3
1.8
.9
.95
.9
.9
890
90
5
ca. 5
5
0
72 0
0
09a)
23 09a)
09a)
89b)
9b)
0
8 0
8 0
9
16
4.8
H2SO4
KF
H2SO4
10
16
20
2.2
4.0
2.0
0.06
36d
0
0
Pt electrodes, undivided cell.
a
Based on recovered starting material; the balance of products were intractable tars.
By 1H NMR inspection of the crude product.
See Section 2 for assignment of structure.
b
c
d
Crude product appeared to be, by 1H NMR, a mixture of nuclear mono-methoxylated products from which 10 was isolated in 27% yield.

J. H. P. Utley, G. G. Rozenberg / Tetrahedron 58 ꢀ2002) 5251±5265
Table 3. Oxidation potentials and chemical shifts for 2- and 6- substituted naphthalenes
5253
d 013C)
d 01H)
a
Ep /SCE
Compound
6-Substituent
2-Substituent
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
H
CH3
OH
OCH3
EtOSO2
H
CH3
CH3
CH3
CH3
CH3
C6H5
4-CH3´C6H4CH2
4-CH3O´C6H4CH2
4-Cl´C6H4CH2
4-CN´C6H4CH2
C6H5
4-CH3´C6H4CH2
4-CH3O´C6H4CH2
4-Cl´C6H4CH2
4-CN´C6H4CH2
1.75
1.70
1.43
1.41
2.17
1.82
1.83
1.7941.28
1.82
1.84
1.41
1.42
1.41
1.50
1.47
21.64b
21.57b
21.93
21.54
21.98
42.14
41.80
4.08
41.42
42.20
41.99
41.57
41.094.07
41.094.09
41.68
±
±
2.47
2.45
2.53
4.13
4.09
H
H1H
H
4.08
4.20
3.90
4.06
H
CH3O
CH3O
CH3O
CH3O
CH3O
4.11
Irreversible oxidation in all cases at substrate concentration 2±3 mM, nˆ0.6 V s21, CH3CN±Bu4NBF4 00.1 M), Pt anode 00.5 mm diameter), Ag/AgNO3
00.1 M). In CDCl3, vs. TMS, at 63 MHz 013C) and 250 MHz 01H).
a
Calibrated against the reversible redox couple for 9,10-diphenylanthracene 0E0ˆ0.85 V vs. Ag/Ag1, 1.22 V vs. SCE).13,14
b
Ref. 15.
consistent. However, in the radical±cation of the 2-methyl-
naphthalenes electron donation by the 6-methoxy group
does not, by analogy with, e.g. 4-methoxytoluene,
apparently promote deprotonation of the side chain to a
point where it competes with either radical±cation/radical±
cation or radical±cation/substrate dimerisation.
in the 2-ArCH2 group. The largest shift in 13C chemical
shift is caused by the change from 2-CH3 to 2-CH2Ar,
presumably a consequence of the electronegative sp2 carbon
of the phenyl group. Within the range of compounds 2f±2j
the 4-CN group causes a relatively small down®eld shift
0Ddˆ0.06 ppm) whereas 4-MeO causes a larger up®eld
shift 0Ddˆ0.86 ppm).
It is appropriate therefore to attempt to assess quantitatively
the effect of substituents on the aromatic nucleus and at the
side-chain. Oxidation potentials were measured by cyclic
voltammetry as a measure of the substituents' in¯uence
on radical±cation stability 0Table 3). 13C NMR chemical
shifts for the 2-CH2Y carbons in selected compounds of
type 2 were also measured as an indicator of the effect of
substituents on the polarity of that carbon atom 0Table 3).
However, these are initial state effects and it is not clear
what the polar effect would be on the stability of the doubly
benzylic radical formed by deprotonation of the benzylic
protons in the radical±cations of compounds 2f±2o.
Such a radical would undoubtedly be stabilised by spin
delocalisation but it is not obvious whether such stabilisa-
tion would be expected to be more or less than that of the
parent radical±cation by 6-substitution 02k±2o). At least for
XˆH 02f±2j) it is possible that stabilisation of the doubly
benzylic radical, by spin delocalisation, would enhance
The results in Table 3 make clear the polar effects of the
substituents. As expected, the oxidation potentials are,
relative to that of the parent 2-methylnaphthalene, signi®-
cantly lowered by electron donating substituents at the
6-position and increased by the electron-withdrawing
EtOSO2 substituent. Furthermore, the changes in oxidation
deprotonation of the radical±cationÐsee Scheme
0YˆAr).
1
Within the series XˆH and XˆOMe the Ep values for
oxidation are essentially unaffected by substitution in the
remote 2-ArCH2 group 0Table 3) as shown by the results
for compounds 2f±2o. Substitution in the 2-ArCH2 group
does not, therefore, relay its ground state electronic effect to
the naphthalene nucleus despite having a profound effect at
0
potential correlate roughly with sR 0Fig. 1). Similarly,
changes in the polarity of the benzylic carbon atom at the
2-position, as measured by 13C chemical shifts, are also
demonstrably linked to substitution in the 6-position and
0
the benzylic carbon. For the plot in Fig. 1, sR values,
derived16 from 13C chemical shifts in substituted benzenes,
were used and gave a rough but discernible correlation of
the data.
The conclusion from these data is that we may expect to
enhance the acidity of the benzylic protons in the radical±
cations bearing the 2-0CH2C6H4´Z-4) group, by virtue of
stabilisation by spin delocalisation of the resulting doubly
benzylic radical and to ®ne-tune it by substitution at the
4-position. However, unlike the 4-methoxytoluene radical±
cation case, side-chain deprotonation may face severe
competition from the dimerisation and nuclear substitution
pathways. In any event, the predictions concerning
the effects of the different types of substitution on the
Figure 1. Polar effects on oxidation potentials.

5254
J. H. P. Utley, G. G. Rozenberg / Tetrahedron 58 ꢀ2002) 5251±5265
Scheme 1.
competition between side-chain and nuclear nucleophilic
substitution and dimerisation need testing by experiment.
between DDQ and the series of 2- and 6-substituted
naphthalenes, as a comparison between a chemical oxidant
and the electrochemical alternative. Key results are
summarised in Table 5.
1.4. Anodic oxidation of 2-CH2Ar substituted
naphthalenes
Side-chain oxidation by DDQ is ef®cient where an electron-
donating substituent is present at the 6-position. Further-
more, products at a lower level of oxidation 0e.g. 2p and
2q) are converted smoothly into the 2-carboxaldehydes. The
parent 2-methylnaphthalene and compound 2e, with the
strongly electron-withdrawing EtO´SO2 substituent, do not
react with DDQ under the conditions used. A particularly
signi®cant ®nding is the conversion in dry benzene of
compound 2d into the side-chain oxidised DDQ adduct 15.
Key results from constant current preparative-scale
electrolysis of a selection of 2-CH2Ar substituted analogues
are summarised in Table 4. The preparative outcome is
disappointing. A much lower current density 0and a larger
anode to compensate) was used in an attempt to suppress
dimerisation. This appeared to be effective, but nuclear
substitution was preferred except for the 2-04-methoxy-
benzyl) derivative 02h) where a low yield of side-chain
methoxylated product 014) was obtained.
1.5. Side chain substitution via DDQ oxidation
2-Methoxy-6-methylnaphthalene 02d) is oxidised to
2-methoxy-6-naphthalene carboxaldehyde in 90% yield by
DDQ in acetic acid solution whereas 2-methylnaphthalene
does not react under the same conditions.17 Consequently, a
systematic exploration was undertaken of the reactions
Table 4. Preparative anodic oxidation of 2-CH2Ar substituted naphthalenes
Substrate 04-Z)
Products 0%)a
S
Conversion 0%)
Nuclear
11 12 13
Side-chain
14
2f 0H)
6
5
±
±
6
±
31
54
32
±
±
±
60
43
12
92
90
.95
.95
2g 0CH3)
2h 0CH3O)
2i 0Cl)
1.6. Mechanistic rationalisation
12
±
9±
40
Intractable oilsb
The main facts to be explained concerning the electro-
oxidation of 6-substituted-2-alkyl naphthalenes are:
2k±2o
Substrate concentration 0.05 M, divided cell, Pt plate anode 06.25 cm2),
carbon rod cathode, constant current 06.4 mA cm22, 8 F), MeOH±CH2Cl2
010% v/v) ±KF 00.2 M).
1. Direct side-chain oxidation is not achieved in the
6-substituted-2-methyl series.
2. For electron-rich derivatives that gave identi®able
products 02-methoxy-6-methylnaphthalene, 2d, and 2-
methylnaphthalene, 2a) the main products were the
a
Isolated yield.
1H NMR of the crude product indicated traces of naphthoquinones. For an
b
electrolysis in MeOH±CH2Cl2±H2SO4 solution 0see Table 2) some
coupling products 0,5%) were evident but not isolated.

J. H. P. Utley, G. G. Rozenberg / Tetrahedron 58 ꢀ2002) 5251±5265
Table 5. DDQ oxidation of 6-X-2-CH2Y substituted naphthalenes 02)
5255
Substrate
Product 0% yield)a
Re¯ux 0h)
Conversion 0%)
Compound number
X
Y
DDQb
3 0YˆH)
2a
2b
2d
2d
2p
2q
2e
H
CH3
H
H
H
H
OH
Oac
H
3
2
3
18
4
4
8 days
4
4
4
±
0
.95
.95
50c
CH3O
CH3O
CH3O
CH3O
EtOSO2
9
015, 70%)
95
95
0
0
d
1
±
1.5
1.5
3
.95
.95
50e
In acetic acid±water 010±15% v/v).
Isolated yields.
Molar equivalents.
a
b
c
A further 30% was a mixture of products hydroxylated at both side-chains.
In dry benzene, overall conversion not measured.
A mixture of hydrolysed sulfonate ester and starting material was obtained.
d
e
dimers 9a and 9b 023 and 72%, respectively). Dimerisa-
tion is suppressed in oxidation of the least electron-rich
derivative 0ethyl 6-methyl-2-naphthalenesulfonate, 2e),
in which case nuclear substitution is observed to give 10.
not in principle affect the competition between the rates of
Á
deprotonation of the radical±cations vis a vis dimerisation
and nucleophilic substitution. For the 2-alkylnaphthalenes
side-chain substitution is clearly highly disfavoured in
comparison with the alternative pathways, even with
6-methoxyl substitution, probably meaning that stabilisation
of the ®rst-formed radical±cation is more important than
stabilisation of the neutral benzyl radical. Furthermore,
even the possibility of substantial stabilisation by deproto-
nation to a doubly benzylic radical, as for the 2-arylbenzyl
series, does not promote side chain substitution in favour of
alternative pathways.
3. In the 2-benzylnaphthalene series, 2f±2i, 4-substitution
in the benzyl group does not in¯uence potentials for
oxidation of the naphthalene nucleus although 13C
chemical shifts indicate that the polarity of the benzylic
carbon 0C-2) is in¯uenced. However, anodic oxidation of
these compounds gives mainly nuclear substitution
except for 2-04-methoxybenzyl)naphthalene 02h), which
gives a relatively small amount of side-chain oxidation
012%).
4. However, for the relatively electron-rich derivatives 02,6-
dimethylnaphthalene, 2b and 2-methoxy-6-methyl-
naphthalene, 2d) ef®cient side-chain oxidation is
achieved by reaction with DDQ in acetic acid. In dry
benzene, an adduct 015) formed between the substrate
and DDQ can be isolated in good yield.
1.7. Direct anodic side-chain oxidationÐdeprotonation
of methylarene radical±cations
Kinetic measurements of the deprotonation of arene radical
cations in water8 and in acetonitrile18 have been reported,
the latter case being in second order reactions with pyridine
derivatives. In both examples electron donor substituents
cause radical cations derived from electron-rich methyl-
arenes to deprotonate more slowly. In water the radical±
cations were formed by irradiation, whereas in acetonitrile
they were formed by oxidation with Fe0III) complexes and
reacted with pyridine derivatives. In neither case were the
benzyl radicals further oxidised to benzyl cations, hence
stabilisation of the initial radical±cations by electron donors
dominated. In our electrochemical experiments, the benzyl
radicals formed by deprotonation of radical±cations are
rapidly oxidised further by a second radical cation in homo-
geneous electron transfer 0the DISP mechanism, Scheme 1)
and whether or not stabilisation of the benzyl cations
encourages deprotonation has to be considered. Certainly
for anodic oxidation of toluenes electron donating sub-
stituents, especially methoxyl, favour deprotonation in
preparative experiments. However, the subsequent oxida-
tion of the benzyl radicals formed by deprotonation should
1.8. Dimerisation vs nuclear substitution
In the 2-methyl-6-X-naphthalenes electron withdrawal at
the 6-position 0XˆEtOSO2) apparently promotes nuclear
substitution as opposed to dimerisation and deprotonation.
In contrast, stabilisation of the ®rst-formed radical±cation
by electron donation 0XˆMeO, Me) favours dimerisation
over the alternative pathways. It is tempting to explain the
ready dimerisation in terms of delocalisation of the positive

5256
J. H. P. Utley, G. G. Rozenberg / Tetrahedron 58 ꢀ2002) 5251±5265
charge reducing coulombic repulsion between two reacting
radical±cations. However, whilst relevant calculations
indicating charge density have been carried out 0described
later) we have no information on the corresponding spin
densities that must control dimerisation. A relatively simple
view of why dimerisation at the 4-position is favoured is
expressed in structure 17, that of the dihydro intermediate,
which shows how the two positive charges are stabilised by
the methoxyl groups.
acceptor ability of the quinone, re¯ected in its reduction
potential 00.5 V vs SCE in MeCN25) and the donor ability
of the aromatic hydrocarbon, re¯ected in its oxidation
potential. Based on this compelling precedent we would
expect the formation of relatively stable complexes between
DDQ and the more electron rich naphthalene derivatives.
Reaction between DDQ and 2-methyl- or 2-benzylnaph-
thalenes is relatively fast 04 h) in aqueous acetic acid 0at
808C) and slow 0ca. 3 days) in dry benzene. In both cases
the initial solutions are dark green, indicating CT complexa-
tion, and as reaction proceeds the colour fades. In aqueous
acetic acid side-chain oxidation is ef®cient whereas in dry
benzene the adduct 15 is obtained. These observations are
consistent with the mechanistic possibilities set out in
Scheme 2 for the oxidation of 2d. It is commonly supposed
that DDQ and related oxidations proceed via hydride
transfer and that route is included in Scheme 2 for com-
pleteness. However, because of the likely formation of CT
complexes we also propose that intramolecular deproto-
nation of the radical±cation of 2d, in the CT complex, is
now facile because the base 0the quinone radical±anion) is
juxtaposed. In dry aprotic solvent, the radical pair so
produced collapses to form the adduct 15. Otherwise,
further electron transfer, presumably from a second
molecule of DDQ, produces the benzyl cation leading by
side-chain substitution and further similar steps to the
aldehyde. The direct hydride transfer route will lead to the
same products. It has been shown 0Table 5) that the side-
chain substituents ±CH2Nu 0NuˆOH, OAc) are further
oxidised as proposed. Constant potential oxidation of non-
stoichiometric mixtures of substrate and DDQ reveals that
spent DDQ can be regenerated in situ and ef®cient side-
chain oxidation of electron-rich 2-methyl and 2-benzyl-
naphthalenes results.26 These experiments will be described
in full elsewhere.
A similar relationship is found for the dimerisation19,20 of
the radical±anions of esters of cinnamic acid. In that case
the more easily reduced esters gives rise to radical±anions
that dimerise the fastest and in contrast they react with an
electrophile 0proton) the slowest. In each case the relation-
ship between reduction potential and log k 0for dimerisation
or for protonation) is linear but of opposite slope! A
theoretical treatment of this competition has been
attempted.20,21
Eberson and co-workers22 calculated atomic charges in a
series of methyl-substituted naphthalenes radical±cations.
Most relevant for us is the result for 2,6-dimethylnaph-
thalene, given in structure 18. The relatively high charge
densities at the 1 and 4 positions are consistent for the
anodic reaction of 2e with the observed formation by
nucleophilic attack of 10. After nucleophilic attack on the
radical cation subsequent further oxidation would give the
intermediate 19 in which the 2-methyl group has a
stabilising role.
1.9. Oxidation with DDQ
DDQ forms charge transfer 0donor±acceptor) complexes
0CT), usually highly coloured, with aromatic hydrocarbons.
The stability of the complexes is a function23,24 of the
Scheme 2.

J. H. P. Utley, G. G. Rozenberg / Tetrahedron 58 ꢀ2002) 5251±5265
5257
Scheme 3.
1.10. The naphthylarylmethane derivatives; routes to
starting materials and intermediates
platinum wire, which was positioned about 0.5 cm from the
working electrode. Three different types of reference elec-
trodes were used. An Ag/AgBr electrode was freshly made
prior to measurement by electroplating silver bromide onto
the surface of a silver wire from a saturated KBr solution by
passing current between the silver wire 0anode) and a carbon
rod 0cathode). An Ag/Ag1 electrode was constructed by
inserting a silver wire into an acetonitrile solution contain-
ing silver nitrate 00.1 M) that was divided from the bulk
solution using `cracked' glass. These electrodes were cali-
brated with regard to SCE using the reversible oxidation
potential 0E0, ®rst wave) of 9,10-diphenylanthracene as
standard after a set of measurements; the E0 value for
9,10-diphenyl anthracene in acetonitrile/tetrabutylammo-
nium tetra¯uoroborate 00.1 M) is known13,14 to be 0.85 V
vs SCE.
The investigation required the synthesis of several new
compounds and the routes used are summarised in Scheme
3. The Grignard addition step gave, in some cases an
unexpected result, whereby addition of a Grignard reagent
to an aldehyde occurred but the adduct was oxidised by the
aldehyde to give a naphthylaryl ketones. This reaction,
reminiscent of the Oppenauer oxidation of alcohols by
alkoxides, appears to be favoured when the Grignard
reagent is electron rich although the pattern is not
completely clear.
The conversion of naphthylarylmethanols into the naph-
thylarylmethanes proceeded ef®ciently on treatment with
sodium borohydride in tri¯uoroacetic acid. Intense colours
were observed, presumably due to intermediate naphthyl-
arylmethyl cations, and these faded as reduction took place.
Fortunately the unexpected formation of naphthylaryl
ketones did not hamper preparation of the desired naphthyl-
arylmethanes because the ketones could be reduced sequen-
tially by sodium borohydride in tri¯uoroacetic acid. The
reduction was not completely selective in those cases
where nitrile substituents were present as competing reduc-
tion to amines took place. Full details are given in the
Section 2.
The solvents used were normally freshly distilled and kept
over freshly activated molecular sieves to ensure dryness.
Supporting electrolytes, usually tetraalkylammonium salts,
were dried in an oven 0,1208C) for at least 24 h or in a
reduced pressure oven 0,508C, ,20 mmHg) for 8 h prior to
use.
2.2. Controlled potential electrolysis
Preparative scale electrochemical reductions were carried
out using a DT 2101 Hi Tek potentiostat with an electronic
charge integrator constructed in the Department's electronic
workshop. Conventional glass cells were used, typically
equipped with either Pt foil or Pt disc anodes and carbon
counter electrodes with the anode and cathode compart-
ments separated by a glass sinter for electrolysis in divided
cells. The reference electrode was Ag/AgBr positioned as
closely as possible to the working electrode. The electro-
lytes were stirred magnetically and the reaction was kept in
an inert atmosphere by the slow bubbling of nitrogen
through the solution. Constant temperature conditions
were maintained either by using cells with cooling jacket
designs or cells immersed in heated oil baths.
2. Experimental
2.1. Electrochemical experiments
Cyclic voltammetric experiments 0CV) were performed
using a VersaStat EG&G Princeton Applied Research
potentiostat with Model 270/250 Research Electrochemistry
Software v 4.00.
The cells were equipped with either a platinum bead elec-
trode, which was heated over a Bunsen ¯ame until red-hot
between separate runs, or platinum micro disc electrodes
with a diameter of 0.5 or 0.75 mm, which were washed
with acetone, dried and polished using `Emery' polishing
paper between runs. The counter electrode used was a coiled
2.3. Controlled current electrolysis
To ensure an even current gradient the two-electrodes were

5258
J. H. P. Utley, G. G. Rozenberg / Tetrahedron 58 ꢀ2002) 5251±5265
positioned parallel to each other. The distance between the
electrodes was large enough for ef®cient mass transport but
close enough to ensure low solution/electrolyte resistance.
Jˆ7.3 Hz, Ar-H), 7.63 0d, 1H, Jˆ6.4 Hz, Ar-H). 13C NMR
063 MHz, CDCl3): dˆ21.54, 55.35, 105.82, 118.73, 126.71,
126.82, 128.69, 128.83, 129.31, 132.81, 133.12, 157.18.
2.6.2. 2-Methyl-6-naphthol <2c). 2-Methoxy-6-methyl-
naphthalene 02d) 05.0 g; 0.029mol) was dissolved in dry
dichloromethane 080 ml) under nitrogen. Boron tribromide
02.0 ml; 20 mmol) was added with a syringe while stirring.
The solution was re¯uxed for 2 h and allowed to cool to
room temperature. An aqueous solution of 2 M NaOH
0100 ml) was added dropwise and stirred vigorously for
30 min. The organic layer was separated off and the aqueous
phase was made acidic with conc. HCl. The aqueous mother
liquor was extracted with dichloromethane 03£40 ml). The
organic phases were combined and washed ®rstly with
water 05£100 ml) in order to remove H3BO3, and then
with sat. sodium bicarbonate 02£50 ml). The organic
phase was dried over MgSO4 and ®ltered. The solvent was
evaporated off and the remaining brown residue recrystal-
lised from chloroform yielding a dark pink precipitate. After
®ltration the solid was recrystallised from absolute ethanol
yielding a rose-white precipitate which was ®ltered and
dried in vacuo yielding the title compound 04.53 g;
0.286 mol; 98%) as white powder, mp 118±1238C IR
0KBr) 0cm21): 3284, 3045, 2941, 1606, 1390, 1208, 1175,
862, 821, 811, 648. UV 0MeCN): l 01, dm3 mol21 cm21)231
2.4. Instruments
1H NMR spectra were recorded either on a Bruker WP-80
080 MHz), a Bruker AM-250 0250 MHz) or Bruker AMX-
600 0600 MHz). Solution 13C NMR spectra were also
recorded on the Bruker AM-250 0250 MHz) and the Bruker
AMX-600 0600 MHz). Solid state 13C NMR spectra were
obtained from the Solid State NMR Service of the ULIRS
based at University College London, and recorded on a
Bruker MSL-300 075 MHz). Mass spectra were obtained
on a Kratos MS-50RF instrument with a Kratos DS90 data
requisition system. Elemental analysis data were obtained
from the Elemental Analysis Service at University College
London.
UV-HPLC analytical experiments were conducted using a
KippAnalytica, 9209 Autosampler connected to
a
ConstaMetric III pump, feeding a PhaseSep, Spherisorb
S5 ODS2 025 cm£4.6 mm) Reverse phase column. A
Spectromonitor III, Model 1204A set at 240 nm, was used
as the UV-detector and the chromatograph recorded on a
Shimadzu, Chromatopac C-R1B. Flash chromatography
was performed using Sorbsil C 40/60H silica gel. Thin
layer chromatography was performed using Merck DC-
Alufolien Kieselgel 60 F254 plates with a thickness of
0.2 mm.
1
030,500), 273 05300), 336 nm 02500). H NMR 0250 MHz,
CD2Cl2): dˆ2.47 0s, 3H, Ar-CH3), 5.890br. s, 1H, Ar-O H),
7.06±7.13 0m, 2H, Ar-H), 7.28 0dd, 1H, Jˆ8.4, 1.7 Hz, Ar-
H), 7.55 0s, 1H, Ar-H), 7.58 0d, 2H, Jˆ8.5 Hz, Ar-H), 7.66 0d,
1H, Jˆ8.7 Hz, Ar-H). 13C NMR 063 MHz, CD2Cl2):
dˆ21.93, 110.04, 118.52, 126.91, 127.43, 129.55, 129.82,
129.88, 133.57, 133.91, 153.74. MS; m/z 0%)ˆ158.1 0M1,
100), 141.1 03), 128.1 09), 115.0 02). MS; m/z, M1 158.0735
0calcd for C11H10O 158.07317).
Melting points were measured on a glass slide using a
Reichert microscope melting point apparatus. Infrared
absorption spectra were recorded on a Perkin±Elmer 1600
series FT-IR spectrometer. Ultraviolet spectra were
recorded on a Perkin±Elmer Lambda2 UV/Vis spectro-
meter.
2.6.3. Sodium 6-methyl-2-naphthyl sulfonate, <sodium
menasylate). 2-Methylnaphthalene 02a) 076.0 g; 0.53 mol)
was heated until it melted 0408C) and conc. H2SO4 098%;
76.0 g; 40 ml) was added slowly to the stirred suspension.
The temperature rose to 1408C during the addition and was
kept between 90 and 1208C for an additional 6 h. The dark
blue slurry was poured into ice-cold water 0300 ml). By-
products were extracted and separated off with benzene
02£50 ml) and the aqueous phase was added to a sat.
NaCl solution 0500 ml) resulting in an off-white precipita-
tion. The slurry was additionally stirred for 16 h and then
cooled to about 58C. After ®ltration the grey clay was dried
in vacuo at 1408C until dry. The solid was suspended in
acetone 0300 ml) and stirred vigorously for 1 h. The dark
blue slurry was ®ltered and the solid was then recrystallised
twice from water 02£1000 ml). The precipitate was ®ltered
and dried in vacuo yielding the title compound 069.0 g;
53%) as grey micro-crystals, mp.3408C 0lit.,28 .2808C).
IR 0KBr) 0cm21): 3054, 1219, 1136, 1102, 1041, 894, 830,
2.5. Preparation of starting materials
Several substrates and reagents were obtained com-
mercially; 2-methoxy-6-naphthalene carboxaldehyde 03d)
was a gift from SmithKline Beecham, Worthing.
2.6. Naphthalenes
2.6.1. 2-Methoxy-6-methylnaphthalene <2d). 2-Methoxy-
6-naphthalene carboxaldehyde 03d) 050.0 g; 0.268 mol) was
added in small portions to a stirred mixture containing
hydrazine 091 ml; 1.876 mol), KOH 051.7 g; 0.923 mol in
diethylene glycol 0420 ml). The mixture was heated slowly
to near re¯ux 0ca. 1658C) resulting in vigorous gas evolution
0N2). After 22 h the pale green slurry was allowed to cool
and poured into stirred ice-water 0600 ml) yielding a white
precipitate which was stirred for an additional hour. The
white precipitate was recrystallised from acetone, ®ltered
and dried in vacuo yielding the title compound 039.7 g;
0.23 mol; 86%) as white micro-needles, mp 75±768C
0lit.,27 768C). UV 0MeCN): l 01, dm3 mol21 cm21)ˆ228
1
740, 700, 656, 616. H NMR 0250 MHz, D2O): dˆ2.52 0s,
3H, Ar-CH3), 7.48 0dd, 1H, Jˆ8.4, 1.5 Hz, Ar-H), 7.72 0s,
1H, Ar-H), 7.83 0dd, 1H, Jˆ8.7 Hz, Jˆ1.8 Hz, Ar-H), 7.91
0d, 1H, Jˆ8.3 Hz, Ar-H), 7.93 0d, 1H, Jˆ8.7 Hz, Ar-H),
8.33 0s, 1H, Ar-H).
1
027,800), 260 04400), 333 nm 01900). H NMR 0250 MHz,
CDCl3):dˆ2.45 0s, 3H, Ar-CH3), 3.86 0s, 3H, Ar-OCH3),
7.08±7.12 0m, 2H, Ar-H), 7.25 0dd, 1H, Jˆ8.4, 1.7 Hz,
Ar-H), 7.50 0d, 1H, Jˆ0.8 Hz, Ar-H), 7.62 0d, 1H,
2.6.4. 6-Methyl-2-naphthalene sulfonic acid, <menasylic
acid). Sodium 6-methyl-2-naphthalene sulfonate 06.0 g;

J. H. P. Utley, G. G. Rozenberg / Tetrahedron 58 ꢀ2002) 5251±5265
5259
28.3 mmol) was heated until re¯ux for 3 h in 2N HCl
040 ml) and allowed to cool slowly to room temperature.
The grey solid was ®ltered off and recrystallised from
ethyl acetate 035 ml). The precipitate was ®ltered and
dried in vacuo yielding the title compound 05.97 g;
26.9mmol; 95%) as colourless crystals, mp 125±128 8C
0lit.,28 118±1218C). IR 0KBr) 0cm21): 3323, 3034, 1376,
ether was evaporated off, giving a crude brown oil which
was recrystallised from ethanol±isopropyl alcohol. The
precipitate was ®ltered and dried in vacuo yielding the
title compound 07.36 g; 76%) as white micro-crystals, mp
84±868C 0lit.,29 86±878C).
2.7.2. 2-Naphthyl 4-methylphenyl ketone <25).
A
1
1200, 1105, 1032, 892, 825, 739, 700, 658, 614. H NMR
Grignard reagent was generated from 2-bromonaphthalene
07.25 g; 0.035 mol) as previously described. A solution of
4-methylbenzaldehyde 08.4 g; 0.07 mol; 2 equiv.) in 50 ml
dry diethyl ether was added dropwise, and the resulting
slurry was allowed to react for 20 h at room temperature.
The mixture was then quenched with cold aqueous 2 M HCl
0500 ml) for 2 h while stirring. After extraction into diethyl
ether 03£70 ml), the separated organic layers were
combined and washed with saturated sodium carbonate
0100 ml). The organic layer was dried over anhydrous
magnesium sulfate for 3 h. After ®ltration the diethyl
ether was evaporated off, giving a crude brown oil which
was distilled. The fraction containing 4-methyl benzyl-
alcohol 03.5 g; bp 1108C/,15 mmHg) was taken off, and
the remaining residue was recrystallised from ethanol±
isopropyl alcohol. The precipitate was ®ltered and dried in
vacuo yielding the title compound 05.6 g; 65%) as off-white
crystals, mp 87±898C. Anal. calcd for C18H14O: C, 87.77%;
H, 5.73%. Found C, 87.83%; H, 5.71%. IR 0KBr) 0cm21):
3048, 2917, 1661, 1590, 1254, 1078, 1033, 845, 820, 773,
753. UV 0MeCN): l 01, dm3 mol21 cm21)ˆ219052,000),
255 037,000), 303 nm 012,000). 1H NMR 0250 MHz,
CDCl3): dˆ2.46 0s, 3H, ±CH3), 7.31 0dd, 2H, Jˆ8.4,
1.6 Hz, Ar-H), 7.54 0td, 1H, Jˆ6.7, 1.5 Hz, Ar-H), 7.60
0td, 1H, Jˆ6.7, 1.5 Hz, Ar-H), 7.78 0dd, 2H, Jˆ6.5,
1.6 Hz, Ar-H), 7.88±7.94 0m, 4H, Ar-H), 8.25 0s, 1H,
Ar-H). 13C NMR 063 MHz, CDCl3): dˆ21.73, 125.92,
126.60, 127.88, 128.24, 129.10, 129.42, 130.41, 131.60,
132.36, 135.28, 143.24, 196.52. MS; m/z 0%)ˆ246.1 0M1,
98), 231.1 012), 127.1 046), 119.1 0100). MS; m/z, M1
246.1046 0calcd for C18H14O 246.1045).
0250 MHz, D2O): dˆ2.52 0s, 3H, Ar-CH3), 7.48 0dd, 1H,
Jˆ8.4, 1.5 Hz, Ar-H), 7.72 0s, 1H, Ar-H), 7.83 0dd, 1H,
Jˆ8.7, 1.8 Hz, Ar-H), 7.91 0d, 1H, Jˆ8.3 Hz, Ar-H), 7.93
0d, 1H, Jˆ8.7 Hz, Ar-H), 8.33 0s, 1H, Ar-H). MS; m/z
0%)ˆ222.0 0M1, 100), 141.1 032), 115.1 012), 113.0 044).
MS; m/z, M1 222.03590calcd for C 11H10O3S 222.0055).
2.6.5. 6-Methyl-2-naphthalene sulfonic chloride.
6-Methyl-2-naphthalene sulfonic acid 021.37 g; 0.088 mol)
was dissolved in stirred dimethyl formamide 0100 ml) under
nitrogen. Thionyl chloride 010 ml) was added dropwise at
room temperature and stirred for 30 min. The mixture was
poured into ice-water yielding a grey precipitate which was
®ltered and dried in vacuo yielding the title compound
018.14 g; 0.0754 mol; 86%) as grey powder, mp 98±998C
0lit.,28 98±998C).
2.6.6. Ethyl 6-methyl-2-naphthalene sulfonic ester <2e).
6-Methyl-2-naphthyl sulfonyl chloride 015.0 g; 0.062 mol)
was added in small portions to an ice-cold stirred solution
containing absolute ethanol 020 ml) and pyridine 010 g). The
mixture was stirred for 3 h and then quenched with aqueous
2 M HCl for 1 h yielding a white precipitate which was
®ltered and dried in vacuo yielding the title compound
08.60 g; 0.034 mol; 55%) as white micro-crystals, mp 65±
708C. Anal. calcd for C13H14O3S: C, 62.39%; H, 5.64%.
Found C, 62.56%; H, 5.71%. UV 0MeCN): l 01,
dm3 mol21 cm21)ˆ228 035,000), 280 05300), 325 nm
0900). 1H NMR 0250 MHz, CDCl3): dˆ1.28 0t, 3H,
Jˆ7.1 Hz, ±CH2±CH3), 2.53 0s, 3H, Ar-CH3), 4.14 0q,
2H, Jˆ7.1 Hz, ±CH2±CH3), 7.43 0dd, 1H, Jˆ8.4, 1.5 Hz,
Ar-H), 7.66 0s, 1H, Ar-H), 7.82±7.88 0m, 3H, Ar-H), 8.43 0s,
1H, Ar-H). 13C NMR 063 MHz, CD3CN): dˆ14.80, 21.98,
67.04, 122.70, 127.06, 128.94, 129.13, 129.42, 130.14,
130.28, 132.26, 135.82, 139.75. MS; m/z 0%)ˆ250.1 0M1,
100), 222.0 078), 141.1 041), 129.1 08), 115.1 018). MS; m/z,
M1 250.0664 0calcd for C13H14O3S 250.06637).
2.7.3. 2-Naphthyl 4-methoxyphenyl ketone <26). To a stir-
red solution containing magnesium turnings 00.60 g;
0.025 mol) in 80 ml dry diethyl ether, about a third of the
required Grignard reagent, prepared in dry diethyl ether
from 2-bromonaphthalene 05.00 g; 0.024 mol), was reacted
with a solution of 4-methoxybenzaldehyde 03f) 06.6 g;
0.05 mol; 2 equiv.) as described above. Work up as before
gave a crude brown oil which was distilled. The fraction
containing 4-methoxy benzylalcohol 03.2 g; bp 142±1458C/
,15 mmHg) was taken off, and the remaining residue was
recrystallised from ethanol±isopropyl alcohol. The precipi-
tate was ®ltered and dried in vacuo yielding the title
compound 04.9g; 64%) as off-white crystals, mp 89±90 8C
0lit.,30 91±938C).
2.7. Naphthyl phenyl ketones and methanols
2.7.1. 2-Naphthyl phenyl methanol <20). To a stirred
solution containing magnesium turnings 01.46 g; 0.06 mol)
in 50 ml dry diethyl ether, about a third of the required
bromobenzene 09.42 g; 0.06 mol) was added. When reaction
was under way the remaining bromobenzene was added in a
rate governed by the resulting effervescence. A solution of
2-naphthalene carboxaldehyde 03a) 06.5 g; 0.04 mol) in
100 ml diethyl ether was added dropwise, and the resulting
slurry was allowed to react for 20 h at room temperature.
The mixture was then quenched with cold aqueous 2 M HCl
0400 ml) for 1 h while stirring. After extraction into diethyl
ether 03£60 ml), the separated organic layers were
combined and washed with saturated sodium carbonate
0100 ml). The organic layer was dried over anhydrous
magnesium sulfate for 3 h. After ®ltration the diethyl
2.7.4. 2-Naphthyl 4-chlorophenyl ketone <27). Reaction
between the Grignard reagent from 2-bromonaphthalene
09.5 g; 0.045 mol) and 4-chlorobenzaldehyde 06.4 g;
0.045 mol) in 70 ml dry tetrahydrofuran gave a crude
brown oil which was recrystallised from ethanol±isopropyl
alcohol. The precipitate was ®ltered and dried in vacuo
yielding the title compound 04.8 g; 41%) as off-white
crystals, mp 122±1248C. Anal. calcd for C17H11OCl: C,
76.55%; H, 4.16%. Found C, 77.01%; H, 4.20%. IR 0KBr)

5260
J. H. P. Utley, G. G. Rozenberg / Tetrahedron 58 ꢀ2002) 5251±5265
0cm21): 3050, 1654, 1586, 1278, 1088, 846, 819, 774, 756.
UV 0MeCN): l 01, dm3 mol21 cm21)ˆ218 051,400), 254
035,900), 334 nm 01700). 1H NMR 0250 MHz, CDCl3):
dˆ7.47±7.66 0m, 4H, Ar-H), 7.79±7.84 0m, 2H, Ar-H),
7.88±7.98 0m, 4H, Ar-H), 8.24 0s, 1H, Ar-H). 13C NMR
063 MHz, CDCl3): dˆ125.60, 126.95, 127.89, 128.50,
128.72, 129.44, 131.49, 131.73, 132.29, 134.54, 135.37,
136.24, 138.87, 195.50. MS; m/z 0%)ˆ266.0 0M1, 32),
231.1 012), 155.0 053), 113.0 0100). MS; m/z, M1
266.0496 0calcd for C17H11OCl 266.0498).
±OCH3), 5.92 0d, 1H, Jˆ2.8 Hz, ±CH±OH), 7.09±7.15
0m, 4H, Ar-H), 7.27 0t, 2H, Jˆ8.0 Hz, Ar-H), 7.37 0dd,
1H, Jˆ8.5, 1.7 Hz, Ar-H), 7.68 0t, 2H, Jˆ8.0 Hz, Ar-H),
7.78 0s, 1H, Ar-H). 13C NMR 063 MHz, CDCl3): dˆ21.07,
55.28, 76.18, 105.78, 118.88, 124.70, 125.36, 126.64,
127.13, 128.72, 129.17, 129.52, 134,02, 137.28, 139.15,
140.99, 157.76. MS; m/z 0%)ˆ278.1 0M1, 100), 215.1
013), 185.1 085), 159.1 067). MS; m/z, M1 278.1308
0calcd for C19H18O2 278.1307).
2.7.8. 2-<6-Methoxy)-naphthyl 4-methoxyphenyl ketone
<24). Similar reaction between 4-methoxy-bromobenzene
013.0 g; 0.07 mol) and 6-methoxy-2-naphthalene carboxal-
dehyde 03d) 010.0 g; 0.05 mol) in 150 ml dry tetrahydro-
furan gave a brown solid which was recrystallised from
ethanol±isopropyl alcohol and then further puri®ed through
silica gel 0grade 40±60) using CHCl3 as eluent. Evaporation
of the Rfˆ0.4 fractions and drying in vacuo yielded the title
compound 02.2 g; 15%) as white crystals, mp 149±1528C
0lit.,31 144.5±1468C).
2.7.5. 2-Naphthyl 4-cyanophenyl ketone <28). Similar
reaction between 2-bromonaphthalene 014.5 g; 0.07 mol)
and 4-cyanobenzaldehyde 09.2 g; 0.07 mol) in 70 ml dry
tetrahydrofuran gave a crude brown oil which was recrys-
tallised from ethanol±isopropyl alcohol. The precipitate
was ®ltered and dried in vacuo yielding the title compound
04.3 g; 17%) as off-white crystals, mp 96±998C. IR 0KBr)
0cm21): 3056, 2230, 1654, 1623, 1280, 824, 776, 764, 700.
UV 0MeCN): l 01, dm3 mol21 cm21)ˆ222 056,100), 253
1
041,400), 295 nm 011,900). H NMR 0250 MHz, CDCl3):
2.7.9. 2-<6-Methoxy)-naphthyl 4-chlorophenyl ketone
<29). 6-Methoxy-2-bromo naphthalene 03.00 g; 0.0126 mol)
and 4-chloro-benzaldehyde 01.83 g; 0.013 mol) in 20 ml dry
tetrahydrofuran were reacted together via the Grignard
reagent to give a brown oil which was recrystallised from
ethanol±isopropyl alcohol. The title compound 01.4 g; 37%)
was obtained as pale yellow crystals, mp 148±1508C. IR
0KBr) 0cm21): 3447, 2926, 1649, 1622, 1282, 1214, 863,
842, 816, 747. UV 0MeCN): l 01, dm3 mol21 cm21)ˆ227
039,900), 263 033,700), 316 nm 013,500). 1H NMR
0250 MHz, CDCl3): dˆ3.96 0s, 3H, ±OCH3), 7.19±7.26
0m, 2H, Ar-H), 7.46±7.52 0m, 2H, Ar-H), 7.77±7.84 0m,
3H, Ar-H), 7.88±7.94 0m, 2H, Ar-H), 8.17 0s, 1H, Ar-H).
13C NMR 063 MHz, CDCl3): dˆ55.52, 105.89, 119.92,
126.42, 127.21, 128.69, 129.56, 131.08, 131.33, 131.43,
131.91, 132.43, 136.59, 137.18, 138.61, 159.91, 195.33. MS;
m/z 0%)ˆ296.1 0M1, 100), 185.1 084), 157.1 019), 114.0 015).
MS; m/z, M1 296.0598 0calcd for C18H13O2Cl 296.0604).
dˆ7.53±7.68 0m, 2H, Ar-H), 7.79±7.99 0m, 8H, Ar- H),
8.21 0s, 1H, Ar-H). 13C NMR 063 MHz, CDCl3):
dˆ115.73, 118.08, 125.32 126.95, 127.23, 127.73, 127.82,
127.96, 128.83, 128.96, 129.59, 130.32, 132.29, 133.71,
135.67, 141.68, 195.06. MS; m/z 0%)ˆ257.1 0M1, 18),
155.0 044), 127.1 048), 104.0 0100). MS; m/z, M1
257.0840 0calcd for C18H11NO 257.0841).
2.7.6. 2-<6-Methoxy)-naphthyl phenyl methanol <21).
Reaction between the Grignard reagent prepared from
bromobenzene 09.42 g; 0.06 mol) and 6-methoxy-2-naph-
thalene carboxaldehyde 03d) 010.0 g; 0.05 mol) in 150 ml
diethyl ether gave a crude brown oil which was recrystal-
lised from ethanol±isopropyl alcohol. The precipitate was
®ltered and dried in vacuo yielding the title compound
09.53 g; 72%) as white micro-crystals, mp 71±738C. IR
0KBr) 0cm21): 3356, 3057, 1631, 1605, 1483, 1166, 1028,
749, 700. UV 0MeCN): l 01, dm3 mol21 cm21)ˆ232
1
052,500), 262 05600), 330 nm 01500). H NMR 0250 MHz,
2.7.10. 2-<6-Methoxy)-naphthyl 4-cyanophenyl ketone
<30). Similar reaction between 6-methoxy-2-bromonaphtha-
lene 09.5 g; 0.04 mol) and 4-cyanobenzaldehyde 09.2 g;
0.07 mol) gave the title compound 04.3 g; 38%) as off-
white crystals, mp 125±1288C. Anal. calcd for
C19H13NO2: C, 79.42%; H, 4.56%; N, 4.88%. Found C,
79.85%; H, 4.72%; N, 4.89%. IR 0KBr) 0cm21): 3056,
2234, 1652, 1621, 1480, 1296, 1282, 1214, 1137, 1016,
CDCl3): dˆ2.43 0d, 1H, Jˆ1.9Hz, ±CH±O H), 3.890s, 3H,
±OCH3), 5.94 0s, 1H, ±CH±OH), 7.09±7.15 0m, 2H, Ar-H),
7.24±42 0m, 6H, Ar-H), 7.68 0`t', 2H, Jˆ8.0 Hz, Ar-H),
7.77 0s, 1H, Ar-H). 13C NMR 063 MHz, CDCl3): dˆ55.30,
76.32, 105.79, 118.93, 125.04, 125.36, 126.67, 127.19,
127.54, 128.48, 128.71, 129.53, 134.06, 139.01, 143.84,
157.81. MS; m/z 0%)ˆ264.1 0M1, 100), 215.1 09), 185.1
023), 159.1 089). MS; m/z, M1 264.1151 0calcd for
C18H16O2 264.1150).
874, 850, 803, 764, 710. UV 0MeCN):
l
01,
dm3 mol21 cm21)ˆ236 044,800), 320 nm 014,200). 1H
NMR 0250 MHz, CDCl3): dˆ3.96 0s, 3H, ±OCH3), 7.16±
7.26 0m, 2H, Ar-H), 7.73±7.94 0m, 7H, Ar-H), 8.14 0d, 1H,
Jˆ1.4 Hz, Ar-H). 13C NMR 063 MHz, CDCl3): dˆ55.52,
105.94, 115.41, 118.11, 120.12, 126.08, 127.44, 127.58,
129.66, 130.14, 131.16, 131.52, 132.19, 132.32, 137.48,
142.03, 160.20, 194.78. MS; m/z 0%)ˆ287.1 0M1, 100),
185.1 089), 157.1 022), 113.0 028). MS; m/z, M1 287.0942
0calcd for C19H13NO2 287.0946).
2.7.7. 2-<6-Methoxy)-naphthyl 4-methylphenyl methanol
<22). Reaction between the Grignard reagent prepared form
4-methyl bromobenzene 012.0 g; 0.07 mol) and 6-methoxy-
2-naphthalene carboxaldehyde 03d) 010.0 g; 0.05 mol) in
100 ml diethyl ether gave a crude yellow solid which was
recrystallised from ethanol±isopropyl alcohol. The precipi-
tate was ®ltered and dried in vacuo yielding the title
compound 011.6 g; 84%) as white micro-crystals, mp 88±
908C. IR 0KBr) 0cm21): 3312, 2905, 1606, 1508, 1264,
1164, 1030, 859, 816, 773. UV 0MeCN):
l
01,
2.8. Preparation of substituted benzylnaphthalenes
dm3 mol21 cm21)ˆ232 042,400), 262 08000), 331 nm
01600). 1H NMR 0250 MHz, CDCl3): dˆ2.27 0d, 1H,
Jˆ3.4 Hz, ±CH±OH), 2.32 0s, 3H, ±CH3), 3.890s, 3H,
General reduction method. To magnetically stirred
tri¯uoroacetic acid 050 ml) at 08C under nitrogen, sodium

J. H. P. Utley, G. G. Rozenberg / Tetrahedron 58 ꢀ2002) 5251±5265
5261
borohydride 02.0 g; 53 mmol) was carefully added in
portions over 45 min. To this slurry a solution of substrate
0typically 10 mmol) in dry dichloromethane 040 ml) was
added dropwise. As each drop of solution comes in contact
with the slurry, a strong colouration 0the carbocation) was
observed which rapidly disappears. The rate of addition is
governed by the rate of colour discharge. After the mixture
was stirred at room temperature under nitrogen for typically
20 h, it was quenched with ice cooled aqueous 2 M sodium
chloride until alkaline. After extraction into dichloro-
methane 03£60 ml), the separated organic layers were
combined and washed with saturated sodium carbonate
0100 ml). The organic layer was dried over anhydrous
magnesium sulfate for 3 h. After ®ltration the dichloro-
methane was evaporated off, giving a crude solid which
was recrystallised from ethanol or propan-2-ol.
55.36, 105.81, 118.72, 126.14, 127.02, 128.52, 129.07,
133.19, 136.35, 141.30, 157.41. MS; m/z 0%)ˆ248.1 0M1,
100), 217.1 012), 171.1 08). MS; m/z, M1 248.1202 0calcd
for C18H16O 248.1201).
2.8.7. 2-<4-Methylbenzyl)-6-methoxy-naphthalene <34).
2-06-Methoxy)-naphthyl 4-methylphenyl methanol 022)
02.78 g; 10 mmol) was treated according to the general
reduction method to give the title compound 02.38 g;
91%) as greenish plates, mp 99±1028C. IR 0KBr) 0cm21):
3000, 2919, 1625, 1601, 1472, 1261, 1226, 1026, 850, 808,
791, 738. UV 0MeCN): l 01, dm3 mol21 cm21)ˆ235
1
024,000), 261 05900), 335 nm 01500). H NMR 0250 MHz,
CDCl3): dˆ2.31 0s, 3H, ±CH3), 3.890s, 3H, ±OC H3), 4.06
0s, 2H, Ar-CH2-Ar), 7.06±7.13 0m, 6H, Ar-H), 7.26 0dd, 1H,
Jˆ8.4, 1.7 Hz, Ar-H), 7.54 0s, 1H, Ar-H), 7.61±7.67 0m,
2H, Ar-H). 13C NMR 063 MHz, CDCl3): dˆ21.07, 41.57,
55.35, 105.84, 118.74, 126.97, 128.20, 128.94, 129.10,
129.21, 133.19, 135.62, 136.66, 138.25, 157.39. MS; m/z
0%)ˆ262.1 0M1, 100), 247.1 020), 113.0 046). MS; m/z,
M1 262.1358 0calcd for C19H18O 262.1358).
2.8.1. 2-Benzylnaphthalene <31). 2-Naphthyl phenyl
methanol 020) 02.34 g; 10 mmol) was treated according to
the general reduction method. The title compound was
obtained 01.85 g; 85%) as opaque crystals, mp 34±378C
0lit.,32 35.58C).
2.8.8. 2-<4-Methoxybenzyl)-6-methoxy naphthalene <35).
2-06-Methoxy)-naphthyl 4-methoxyphenyl ketone 024)
01.46 g; 5 mmol) was treated according to the general reduc-
tion method to give the title compound 01.18 g; 85%) as
white micro-crystals, mp 95±968C 0lit.,35 103±1048C).
2.8.2. 2-<4-Methylbenzyl)-naphthalene <36). 2-Naphthyl
4-methylphenyl ketone 025) 02.46 g; 10 mmol) was treated
according to the general reduction method to the title
compound 02.13 g; 92%) as pale yellow crystals, mp 53±
568C 0lit.,33 54±568C).
2.8.9. 2-<4-Chlorobenzyl)-6-methoxy naphthalene <40).
2-06-Methoxy)-naphthyl 4-chlorophenyl ketone 029)
00.21 g; 0.7 mmol) was treated according to the general
reduction method to give the title compound 00.18 g;
90%) as off-white micro-crystals, mp 96±988C. UV
0MeCN): l 01, dm3 mol21 cm21)ˆ233 031,200), 260 nm
06700), 331 nm 01700). 1H NMR 0250 MHz, CDCl3):
dˆ3.90 0s, 3H, ±OCH3), 4.090s, 2H, Ar-C H2-Ar), 6.87
0dd, 2H, Jˆ6.6, 2.1 Hz, Ar-H), 7.10±7.190m, 4H, Ar- H),
7.24 0dd, 1H, Jˆ9.2, 1.8 Hz, Ar-H), 7.57 0s, 1H, Ar-H), 7.69
0dd, 2H, Jˆ10.2, 1.8 Hz, Ar-H). 13C NMR 063 MHz,
CDCl3): dˆ41.09, 55.34, 105.83, 114.00, 116.71, 126.87,
126.94, 127.77, 128.23, 129.32, 130.11, 132.32, 133.19,
133.39, 136.85, 157.46, 158.13. MS; m/z 0%)ˆ282.1 0M1,
100), 251.1 010), 216.1 016), 171.1 06), 113.0 07). MS; m/z,
M1 282.0810 0calcd for C18H15OCl 282.0811).
2.8.3. 2-<4-Methoxybenzyl)-naphthalene <37). 2-Naphthyl
4-methoxyphenyl ketone 026) 01.22 g; 4.65 mmol) was
treated according to the general reduction method. The
precipitate was ®ltered and dried in vacuo yielding the
title compound 01.09g; 95%) as green metallic plates, mp
58±608C 0lit.,34 57±588C).
2.8.4. 2-<4-Chlorobenzyl)-naphthalene <38). 2-Naphthyl
4-chlorophenyl ketone 027) 02.67 g; 10 mmol) was treated
according to the general reduction method to give the title
compound 02.48 g; 98%) as off-white crystals, mp 47±508C
0lit.,33 50±518C).
2.8.5. 2-<4-Cyanobenzyl)-naphthalene <39). 2-Naphthyl
4-cyanophenyl ketone 028) 02.57 g; 10 mmol) was treated
according to the general reduction method to give a crude
product that was puri®ed by chromatography through silica
gel 0grade 40±60) using CHCl3 as eluent. Evaporation of the
Rfˆ0.8 fractions and drying in vacuo yielded the title
compound 01.5 g; 63%) as white crystals, mp 115±1188C
0lit.,33 111±1148C).
2.8.10. 2-<4-Cyanobenzyl)-6-methoxy-naphthalene <41).
2-06-Methoxy)-naphthyl 4-cyanophenyl ketone 030)
02.87 g; 10 mmol) was treated according to the general
reduction method to give a crude product, which was puri-
®ed by chromatography through silica gel 0grade 40±60)
using CHCl3 as eluent. Evaporation of the Rfˆ0.7 fractions
and drying in vacuo yielded the title compound 00.5 g; 19%)
as white crystals, mp 109±1118C. IR 0KBr) 0cm21): 3011,
2936, 2226, 1604, 1481, 1259, 1112, 1032, 813, 699. UV
0MeCN): l 01, dm3 mol21 cm21)ˆ244 033,000), 262
012,000), 335 nm 02700). 1H NMR 0250 MHz, CDCl3):
dˆ3.88 0s, 3H, ±OCH3), 4.11 0s, 2H, Ar-CH2-Ar), 7.09±
7.22 0m, 3H, Ar-H), 7.27 0d, 2H, Jˆ8.2 Hz, Ar-H), 7.51
0s, 1H, Ar-H), 7.52 0d, 2H, Jˆ8.2 Hz, Ar-H), 7.65
0dd, 2H, Jˆ8.4, 3.9Hz, Ar- H). 13C NMR 063 MHz,
CDCl3): dˆ41.68, 55.08, 105.62, 118.90, 127.05, 127.16
127.61, 128.88, 129.47, 132.03, 133.22, 134.32, 146.66,
157.47. MS; m/z 0%)ˆ273.1 0M1, 100), 230.1 010), 171.1
2.8.6. 6-Methoxy-2-benzylnaphthalene <33). 2-06-
Methoxy)-naphthyl phenyl methanol 021) 02.64 g;
10 mmol) was treated according to the general reduction
method to the title compound 02.35 g; 95%) as white
micro-crystals, mp 88±918C. Anal. calcd for C18H16O: C,
87.06%; H, 6.50%. Found C, 87.15%; H, 6.57%. IR 0KBr)
0cm21): 2929, 1605, 1387, 1265, 1227, 1174, 1029, 855,
813, 742, 702. UV 0MeCN): l 01, dm3 mol21 cm21)ˆ230
1
027,000), 260 03000), 320 nm 01200). H NMR 0250 MHz,
CDCl3): dˆ3.90 0s, 3H, ±OCH3), 4.10 0s, 2H, Ar-CH2-Ar),
7.09±7.31 0m, 8H, Ar-H), 7.55 0s, 1H, Ar-H), 7.65 0d, 2H,
Jˆ8.3 Hz, Ar-H). 13C NMR 063 MHz, CDCl3): dˆ41.99,

5262
J. H. P. Utley, G. G. Rozenberg / Tetrahedron 58 ꢀ2002) 5251±5265
010). MS; m/z, M1 273.1154 0calcd for C19H15NO
273.1154).
5.90 0d, 2H, Jˆ10.5 Hz, ±CHvCH±), 6.02 0d, 2H,
Jˆ10.5 Hz, ±CHvCH±).
2.9. Preparative scale electrolyses of substituted toluenes
2.10. Preparative scale electrolyses of substituted 2-
methylnaphthalenes <Table 2)
General procedure for controlled current electrolyses. Dry
potassium ¯uoride 00.22 g; 3.8 mmol) was added to 25 ml of
freshly distilled methanol in an undivided cell equipped
with a magnetic stirrer and nitrogen inlet. The substrate
0typically 17.5 mmol) was then added and electrolysis
carried out at constant current 064 mA cm22). The solution
slowly turned pale yellow, and hydrogen evolution was
observed at the counter electrode. The reaction was termi-
nated after the passage of 4.2 F. The solvents were evapo-
rated. The yellow oily residue obtained was quenched with
170 ml water, and then extracted into 150 ml diethyl ether.
After separating off the aqueous layer, the organic layer was
washed thoroughly with saturated sodium carbonate solu-
tion 03£70 ml). The separated ether layer was then dried
0MgSO4). After ®ltration through celite the solvent was
evaporated off. The orange residue obtained was then
distilled under reduced pressure 0,10 mmHg).
These were performed at constant current and the electro-
lytes were either MeOH±KF 00.15 M) or CH2Cl2±MeOH±
H2SO4 080:15:1 v/v). Typical experiments are described
below.
2.10.1. Electrochemical oxidation of 2-methylnaphtha-
lene <2a). 2-Methylnaphthalene 02a) 01.97 g; 13.9 mmol)
was electrolysed in the MeOH±KF electrolyte at a constant
current of 48 mA cm22 and the reaction was terminated
after 5.3 F. The solution rapidly turned dark brown, and
hydrogen evolution was observed at the counter electrode.
The dark brown residue 01.55 g) was then dissolved in 7 ml
petroleum ether 0bp 40±608C) and run through a silica gel
0grade 40±60) chromatographic column with petroleum
ether 0bp 40±608C) as eluent. The ®rst fraction 0Rfˆ0.5)
was identi®ed 0by UV-HPLC) as the starting material and
tars 00.13 g). The second 0Rfˆ0.3, 0.65 g) was identi®ed as a
1
2.9.1. Electrochemical oxidation of 4-methyltoluene <1b).
4-Methyltoluene 01b, 1.86 g; 17.5 mmol) was treated
according to the general method given above. The orange
residue 02.5 g) obtained was distilled under reduced pres-
sure 010 mmHg). The ®rst fraction 0bp ,958C) was
collected as a clear oil 02.1 g; 12.6 mmol, 72%) and was
identi®ed as 4-dimethoxymethyltoluene 05b), bp 93±958C
mixture of dimers and, by H NMR spectroscopy of the
crude fraction, a small amount of side-chain substituted
product. The third fraction 0Rfˆ0.2, 0.35 g) appeared to be
a complex mixture of nuclear oxidation products and
dimers.
2.10.2. The electrochemical oxidation of 2-methoxy-6-
methylnaphthalene <2d). 2-Methoxy-6-methylnaphthalene
02d) 02.19g, 12.7 mmol) was electrolysed in the CH 2Cl2±
1
010 mmHg): H NMR 0250 MHz, CDCl3): dˆ2.34 0s, 3H,
Ar-CH3), 3.30 0s, 6H, ±OCH3), 5.35 0s, 1H, ±CH0OCH3)2,
7.13 0d, 2H, Jˆ7.1 Hz, Ar-H), 7.37 0d, 2H, Jˆ7.1 Hz, Ar-H)
The second fraction 0bp 96±1038C) contained a mixture of
1-dimethoxymethyl-4-methoxymethylbenzene 06, 12%)
and the two isomeric 1,4-dimethoxy-1,4-dimethyl-2,5-
cyclohexadienes 07b, 8b, 14% combined). The yields were
calculated from the integration of characteristic proton
MeOH±H2SO4 electrolyte at
a constant current of
10 mA cm22 and the reaction was terminated after 2.2 F.
The solution rapidly turned dark brown, and hydrogen
evolution was observed at the counter electrode. The dark
brown residue 03.1 g) was then dissolved in 3 ml chloroform
0bp 40±608C) and run through a silica gel 0grade 40±60)
chromatographic column with chloroform as eluent. The
®rst fraction 0Rfˆ0.85) was identi®ed 0by UV-HPLC) as
the starting material and tars 00.24 g). The second
0Rfˆ0.65, 0.78 g, 72%) was identi®ed as a the dimer
07,70-dimethoxy-3,30-dimethyl-1,10-binaphthalene, 9a) and
the third 0Rfˆ,0.4, 0.10 g) fraction as a complex mixture of
nuclear oxidation products.
1
NMR peaks: H NMR 0250 MHz, CDCl3): 6, dˆ3.32 0s,
6H, ±OCH3), 3.35 0s, 3H, ±CH3±OCH3), 4.40 0s, 2H,
±CH2±OCH3), 5.36 0s, 1H, ±CH0OCH3)2, 7.17 0d, 2H,
Jˆ7.1 Hz, Ar-H), 7.37 0d, 2H, Jˆ7.1 Hz, Ar-H). Isomeric
1
products, 7b, 8b, combined: H NMR 0250 MHz, CDCl3):
dˆ1.24 0s, 40% 3H, ±CH3), 1.32 0s, 60% 3H, ±CH3), 3.04
0s, 6H, ±OCH3), 3.17 0s, 40% 3H, ±OCH3), 3.35 0s, 60%
3H, ±OCH3), 5.77 0s, 60% 4H, ±CHvCH±), 5.81 0s, 40%
4H, ±CHvCH±).
7,70-dimethoxy-3,30-dimethyl-1,10-binaphthalene ꢀ9a). For
ring numbering see displayed structure) was obtained as
colourless crystals, mp 225±2278C, Anal. calcd for
C24H22O2: C, 84.18%; H, 6.48%. Found C, 84.10%; H,
2.9.2. Electrochemical oxidation of 4-methoxytoluene
<1c). 4-Methoxytoluene 01c, 2.14 g; 17.5 mmol) was treated
according to the general method. The orange residue
02.97 g) was distilled under reduced pressure. The ®rst frac-
tion 0bp ,1058C 10 mmHg) was collected as a clear oil
02.6 g; 14.3 mmol, 81%) and was identi®ed as 1-dimethoxy-
methyl-4-methoxybenzene, 5c, bp 100±1058C 010 mmHg):
1H NMR 0250 MHz, CDCl3): dˆ3.35 0s, 6H, ±OCH3), 3.79
0s, 3H, Ar-OCH3), 5.34 0s, 1H, ±CH0OCH3)2, 6.87 0d, 2H,
Jˆ6.8 Hz, Ar-H), 7.36 0d, 2H, Jˆ6.8 Hz, Ar-H). The second
fraction 0bp 106±1158C, 10 mmHg) contained 1,1,4-
trimethoxy-4-methyl-2,5-cyclohexadiene 07c, 6%): 1H
NMR 0250 MHz, CDCl3): dˆ1.30 0s, 3H, ±CH3), 3.12 0s,
3H, ±OCH3), 3.24 0s, 3H, ±OCH3), 3.30 0s, 3H, ±OCH3),
6.52%; UV 0MeCN):
l
01, dm3 mol21cm21)ˆ231
068,700), 279010,600), 342 nm 07700). IR 0KBr) 0cm 21):
2918, 2850, 1595, 1500, 1461, 1345, 1267, 1251, 1174,
1136, 1097, 1064, 918, 817, 804. 1H NMR 0250 MHz,
CDCl3): dˆ2.44 0s, 6H, ±CH3), 3.73 0s, 6H, ±OCH3),
7.00±7.25 0m, 4H, Ar-H, H-2 and H-8), 7.41 0d, 2H,
Jˆ8.7 Hz, Ar-H, H-6), 7.62 0s, 2H, Ar-H, H-4), 7.87 0d,
1
2H, Jˆ8.7 Hz, Ar-H, H-5). H nOe enhancement experi-
ment; irradiated dˆ2.44 0±CH3), 7.03 03.6%, H-2), 7.62
03.7%, H-4); 13C NMR 063 MHz, CDCl3): dˆ21.43,
57.11, 114.59, 125.25, 126.89, 128.63, 129.52. MS; m/z
0%)ˆ342.2 0M1, 100), 296.1 029), 171.1 03), 156.1 07),

J. H. P. Utley, G. G. Rozenberg / Tetrahedron 58 ꢀ2002) 5251±5265
5263
147.6 03), 126.0 03), 91.1 013). MS; m/z, M1 342.1619
0calcd for C24H22O2 342.16198).
126.72, 128.96, 129.60, 131.28, 132.43, 132.90, 133.68,
135.30, 139.05, 158.18, 183.41. H nOe NMR 0250 MHz,
1
CDCl3): irradiation at 3.69ppm 0 vC±CH2±Ph); 2.93
04.4%, 6H, ±OCH3), 6.21 01H, ±CO±CHvC), 7.18
06.5%, 2H, Ar-H). MS; m/z 0%)ˆ328.1 0M1, 4), 269.1
0100), 265.0 035), 261.1 046), 247.1 017), 203.1 080),
115.1 019), 105.0 019). MS; m/z, M1 328.0858 0calcd for
C19H17O3Cl 328.08663).
2.10.3. Electrochemical oxidation of ethyl 6-methyl-2-
naphthalene sulfonic ester <2e). Ethyl 6-methyl-2-naph-
thalene sulfonic ester 013a) 01.40 g; 5.25 mmol) was
electrolysed in the CH2Cl2±MeOH±H2SO4 electrolyte at a
constant current of 20 mA cm22 and the reaction was termi-
nated after 2.0 F. The solution rapidly turned dark brown,
and hydrogen evolution was observed at the counter elec-
trode. The dark brown residue 02.5 g) was then dissolved in
3 ml chloroform and run through a silica gel 0grade 40±60)
chromatographic column with chloroform as eluent. The
®rst fraction 0Rfˆ0.7) was identi®ed 0by UV-HPLC and
1H NMR) as the starting material 00.74 g, 64%). The second
0Rfˆ0.5, 0.50 g, 36%) was identi®ed as a mixture of nuclear
mono-methoxylated products, in which ethyl 4-methoxy-6-
methyl-2-naphthalene sulfonic ester 010, 0.40 g, 27%) was
identi®ed. The yield was calculated by integrating charac-
teristic 1H NMR signals. 1H NMR 0250 MHz, CDCl3):
dˆ1.290t, 3H, Jˆ7.1 Hz, ±CH2±CH3), 2.48 0s, 3H, Ar-
CH3), 3.90 0s, 3H, Ar-OCH3), 4.16 0q, 2H, Jˆ7.1 Hz,
±CH2±CH3), 7.43 0d, 1H, Jˆ8.4 Hz, Ar-H, H-4), 7.63 0s,
1H, Ar-H, H-1), 7.83±7.87 0m, 1H, Ar-H, H-5), 8.24 0d, 1H,
Jˆ8.4 Hz, Ar-H, H-3), 8.44 0s, 1H, Ar-H, H-7). The third
0Rfˆ,0.4, 0.27 g) fraction appears to be a complex mixture
of nuclear oxidation products.
2.11.2.
2-<a,4-Dimethoxybenzyl)-naphthalene
<14,
ZˆOMe). Similar electrolysis of 2-04-methoxybenzyl)-
naphthalene 02h, 0.372 g; 1.5 mmol; 0.05 M), to 8.0 F and
similar work-up gave 2-ꢀa,4-dimethoxybenzyl)-naphthalene
014, ZˆOMe, 50 mg; 0.18 mmol; 12%) as an oil which
could not be crystallised. Yields were calculated from the
integration of characteristic 1H NMR signals. 1H NMR
0250 MHz, CDCl3): dˆ3.40 0s, 3H, ±CH0OCH3)-Ar), 3.76
0s, 3H, ±Ph±OCH3), 5.35 0s, 3H, ±CH0OCH3)-Ar, 6.85 0d,
2H, Jˆ8.8 Hz, Ar-H), 7.290d, 2H, Jˆ7.0 Hz, Ar-H), 7.38±
7.46 0m, 3H, Ar-H), 7.75±7.82 0m, 4H, Ar-H).
2.12. Batch oxidations with DDQ17;38;39
General method for side-chain oxidation. To a hot 0ca.
808C), magnetically stirred solution containing acetic acid
0typically 90 ml), water 0typically 10 ml) and the substrate
0typical conc. 0.2 M), 2,3-dichloro-5,6-dicyano-1,4-benzo-
quinone 0DDQ) was added in portions. The reaction mixture
rapidly turned dark green 0CT complexation). The mixture
was then heated and allowed to re¯ux for 4 h, resulting in a
dark red solution 02,3-dichloro-5,6-dicyano-1,4-hydro-
quinone formation). Standard thin layer chromatography
or HPLC techniques were used to monitor the reaction.
The reaction mixture was allowed to cool to room tempera-
ture, prompting a precipitation of the hydroquinone, and the
solvents evaporated off using a rotary evaporator. The
residue was dissolved in chloroform 0typically 80 ml),
®ltered and poured into dilute aqueous hydrochloric acid
0150 ml, 2 M). The organic phase was separated and the
aqueous phase extracted with chloroform 03£40 ml). The
combined organic layer was washed with dilute sodium
bicarbonate 03£80 ml), water 02£60 ml) and dried
0MgSO4). The ®ltered solution was evaporated under
reduced pressure to give the crude product.
2.11. Anodic oxidation of 2-CH2Ar substituted
naphthalenes <Table 4)
The electrolysis conditions are described in a footnote to
Table 4. Products were typically isolated and puri®ed by
¯ash chromatography 0silica grade 40±60) with
chloroform eluent. Their characterisation is exempli®ed
below.
2.11.1. 2-<4-Chlorobenzyl) naphthalene <2i). 00.38 g;
1.5 mmol; 0.05 M) was electrolysed to 8 F in MeOH±
CH2Cl2 010% v/v)±KF 00.2 M) at constant current
040 mA; 6.4 mA cm22). The crude product mixture
obtained was separated and puri®ed by ¯ash chromato-
graphy 0silica grade 40±60) using chloroform as eluent.
Combining and evaporation of the appropriate fractions
0Rfˆ0.65) gave 2-ꢀ4-chlorobenzyl)-1,4-naphthoquinone
013, ZˆCl) 040 mg; 9%) as an oil which after recrystallisa-
tion from ethanol gave colourless crystals, mp 99±1018C
0lit.,36,37 103±1048C).
These procedures are exempli®ed in the following descrip-
tions of the preparation of 6-methoxy-2-naphthalene
carboxaldehyde 03d) from different substrates and the
preparation of the adduct 015) by oxodation with DDQ in
dry benzene.
The fractions 0Rfˆ0.5), after recrystallisation from ethanol,
gave 3-ꢀ4-chlorobenzyl)-4,4-dimethoxynaphthalene-1-ꢀ4H)-
one 012, ZˆCl) 0150 mg; 30%) as opaque needles, mp 144±
1468C. Anal. calcd for C19H17O3Cl: C, 69.40%; H, 5.21%;
Cl, 10.78%. Found C, 69.35%; H, 5.29%; Cl, 11.12%. IR
0KBr) 0cm21): 3104, 2972, 2377, 1638 0strong, broad),
1600, 1461, 1369, 1318, 1246, 1154, 1119, 1035, 892,
2.12.1. Oxidation of 2-methoxy-6-methylnaphthalene
<2d). 2-Methoxy-6-methylnaphthalene 02d) 03.44 g;
0.02 mol; 0.2 M) was treated according to the general oxida-
tion method using 2,3-dichloro-5,6-dicyano-1,4-benzo-
quinone 018.0 g; 0.06 mol; 3 equiv.) that was added in
portions. The crude product mixture was puri®ed by short
column ¯ash chromatography 0silica grade 40±60) using
chloroform as eluent. Collection of the appropriate frac-
tions, evaporation and recrystallisation from ethanol gave
3d 03.35 g; 0.018 mol; 90%) as off-white micro crystals, mp
79±818C 0lit.,35 80±818C).
1
859, 816, 696, 655. H NMR 0250 MHz, CDCl3): dˆ2.93
0s, 6H, ±OCH3), 3.690d, 2H, Jˆ1.6 Hz, vC±CH2±Ph),
6.21 0t, 1H, Jˆ1.6 Hz, ±CO±CHvC), 7.18 0d, 2H,
Jˆ8.6 Hz, Ar-H), 7.33 0d, 2H, Jˆ8.6 Hz, Ar-H), 7.52
0ddd, 1H, Jˆ7.8, 7.0, 1.6 Hz, Ar-H), 7.68±7.78 0m, 2H,
Ar-H), 8.08 0ddd, 1H, Jˆ7.8, 1.6, 0.6 Hz, Ar-H). 13C
NMR 063 MHz, CDCl3): dˆ34.86, 51.43, 98.32, 126.22,

5264
J. H. P. Utley, G. G. Rozenberg / Tetrahedron 58 ꢀ2002) 5251±5265
2.12.2. Synthesis of 2-methoxy-6-naphthalene carbox-
aldehyde <3d) using 2-hydroxymethyl-6-methoxy-naph-
thalene <2p). 2-Hydroxymethyl-6-methoxy-naphthalene
02p) 03.76 g; 0.02 mol; 0.2 M) was treated according to
the general oxidation method using 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone 09.0 g; 0.03 mol; 1.5 equiv.)
that was added in portions. The crude product mixture
was puri®ed by short column ¯ash chromatography 0silica
grade 40±60) using chloroform as eluent. Collection of the
appropriate fractions, evaporation and recrystallisation from
ethanol gave the title compound 03.54 g; 0.019mol; 95%) as
off-white micro crystals.
Roberts 0SKB), and subsequently helpful liaison by Mr Ron
King 0GSK).
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IR 0KBr) 0cm21): 3323, 3034, 1376, 1200, 1105, 1032,
892, 825, 739, 700, 658, 614. 1H NMR 0250 MHz,
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CH2±O), 7.26 0dd, 1H, Jˆ9.0 Hz, Jˆ2.4 Hz, Ar-H7), 7.37
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Acknowledgements
We gratefully acknowledge support from Smith Kline
Beecham 0Worthing), now Glaxo Smith Kline, many help-
ful discussions with Simon Ruddick 0SKB) and Dr David

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