Base-catalysed ring openings of 1,2-diphenylcycloalkanols having five-, six-, seven- and eight-membered rings

Article abstract of DOI:10.1039/a607548g

trans-Isomers of 1,2-diphenylcyclopentanol, 5, 1,2-diphenylcyclohexanol, 6, 1,2-diphenylcycloheptanol, 7, and 1,2-diphenylcyclooctanol, 8, have been prepared as have their acyclic analogues, threo- and erythro-3,4-diphenylhexan-3-ol, 9. All structural assignments are confirmed by X-ray crystal structure determinations and experimentally determined structures are compared with the results of empirical force field calculations which also yield strain energies for each of the compounds. With alkali metal dimsyl-dimethyl sulfoxide or 1,3-diaminopropane with its potassium salt as base, the cycloalkanols are isomerised to enolates of corresponding 1,n-diphenylalkan-1-ones, and the acyclic alkanols cleaved to propylbenzene and the enolate of propiophenone. The products are consistent with a polar mechanism involving collapse of alkoxide to expel a benzylic carbanion, followed by one or more proton transfers to yield the observed products. Rates increase in the order, 6 < 5 ? 7 < 9 < 8, with a spread in reactivities of ca. 10⁶. Logarithms of relative rates correlate poorly with estimates of strain release in the reactions. Correlations are improved by incorporation of estimates of entropy changes associated with ring opening or cleavage, but remain poor. The fate of isotopic labels in the reactions of 2,n,n-trideuterio-1,2-diphenylcycloalkanols. [²H₃]-5, [²H₃]-7 and [²H₃]-8, shows that protonation of the benzylic carbanion is by solvent DMSO for the cyclooctanol, [²H₃]-8, and that competing intramolecular proton transfer occurs in the cycloheptanol, [²H₃]-7, and cyclopentanol, [²H₃]-5. Kinetic isotope effects associated with the labelling patterns are consistent with a change in rate-limiting step from the initial carbon-carbon bond cleavage in the case of 8, to rate-limiting proton transfer in the case of 5.

Full text of DOI:10.1039/a607548g

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Base-catalysed ring openings of 1,2-diphenylcycloalkanols having
five-, six-, seven- and eight-membered rings
Sayid M. Moosavi, Roy S. Beddoes and C. Ian F. Watt *
Chemistry Department, University of Manchester, Manchester, UK M13 9PL
trans-Isomers of 1,2-diphenylcyclopentanol, 5, 1,2-diphenylcyclohexanol, 6, 1,2-diphenylcycloheptanol, 7,
and 1,2-diphenylcyclooctanol, 8, have been prepared as have their acyclic analogues, threo- and erythro-
3,4-diphenylhexan-3-ol, 9. All structural assignments are confirmed by X-ray crystal structure
determinations and experimentally determined structures are compared with the results of empirical force
field calculations which also yield strain energies for each of the compounds. With alkali metal dimsyl–
dimethyl sulfoxide or 1,3-diaminopropane with its potassium salt as base, the cycloalkanols are isomerised
to enolates of corresponding 1,n-diphenylalkan-1-ones, and the acyclic alkanols cleaved to propylbenzene
and the enolate of propiophenone. The products are consistent with a polar mechanism involving collapse
of alkoxide to expel a benzylic carbanion, followed by one or more proton transfers to yield the observed
products. Rates increase in the order, 6 < 5 Ӷ 7 < 9 < 8, with a spread in reactivities of ca. 106. Logarithms
of relative rates correlate poorly with estimates of strain release in the reactions. Correlations are
improved by incorporation of estimates of entropy changes associated with ring opening or cleavage, but
remain poor. The fate of isotopic labels in the reactions of 2,n,n-trideuterio-1,2-diphenylcycloalkanols.
[2H 3]-5, [2H 3]-7 and [2H 3]-8, shows that protonation of the benzylic carbanion is by solvent D M SO for the
cyclooctanol, [2H 3]-8, and that competing intramolecular proton transfer occurs in the cycloheptanol,
[2H 3]-7, and cyclopentanol, [2H 3]-5. K inetic isotope effects associated with the labelling patterns are
consistent with a change in rate-limiting step from the initial carbon–carbon bond cleavage in the case
of 8, to rate-limiting proton transfer in the case of 5.
and reactivity in these carbanion forming reactions has led us to
Introduction
examine the reactions of the 1,2-diphenylcycloalkanols, where
the analogous reaction would, according to Stirling’s classifi-
cation,3 be nucleophile eliminative ring fissions of the class exo
Since tertiary alkoxides are adducts of strongly basic carban-
ions and ketones, studies of their decomposition by C᎐C bond
homolysis or heterolysis provide an alternative aspect on the
mechanisms of these synthetically and biologically important
reactions. We have made a detailed study of decompositions of
the alkoxide of 1,2,3-triphenylpropan-2-ol, 1. Rate and product
data for the reaction in dimethyl sulfoxide (DMSO) solution are
consistent with a collapse of this alkoxide by expulsion of
benzyl anion. The products are toluene, shown to incorporate a
proton from solvent DMSO, and the enolate of 1,2-diphenyl-
ethanone,1 2, formed by deprotonation of the ketone, presum-
ably by dimsyl anion, as shown in Scheme 1. Light and heavy
O᎐C: Cn, yielding enolates of the isomeric linear ketones.
᎐
Variation of reactivity in intramolecular reactions with ring size
is more often studied in reactions involving ring formation,4
and these alkoxide fragmentations afford a rare chance to
examine relative reactivities in ring-openings of other than
small rings which have been studied already (trans-3 and cis-3
by Jencks and Thiblin,5 and trans-4 and cis-4 by Forward et
al.6). Both the cyclopropanols and cyclobutanols are sufficiently
reactive for ring-openings to be observable in aqueous base,
albeit at elevated temperatures in the cyclobutanol case, and in
this protic medium the products observed are ketones rather
than their enolates. Again, the available evidence was consistent
with rate-limiting formation of a benzylic carbanion. Hoff-
mann and Cram,7 however, have shown that with sodium
dimsyl in DMSO solution, equilibration of (Ϫ)-(1R;2R)-cis-
1,2-dimethyl-2-phenylcyclopentanol and (Ϫ)(1S;2R)-trans-
1,2-dimethyl-2-phenylcyclopentanol occurs many times faster
than formation of acyclic material, indicating that carbanion
formation is not rate-limiting in this case.
In this study we compare reactions of the homologous series
comprising 1,2-diphenylcyclopentanol, 5, 1,2-diphenylcyclo-
hexanol, 6, 1,2-diphenylcycloheptanol, 7 and 1,2-diphenyl-
cyclooctanol, 8. We also describe the behaviour of their close
acyclic analogues, threo- and erythro-3,4-diphenylhexanol, 9.
Preparation and structures
Scheme 1 Decompositions of alkoxides of linear and cyclic 1,2-
The normal and medium ring cycloalkanols were prepared by
the reaction schemes which involved addition of phenyllithium
to the corresponding 2-phenylcycloalkanone. In all cases, the
addition yielded a major product alcohol, on steric grounds
expected to be the trans-isomer of the 1,2-diphenylcyclo-
alkanol. 1H NMR spectroscopic evidence was always consistent
diphenylalkanols
atom kinetic isotope effects are consistent with the carbon–
carbon bond cleavage occurring in an initial rate-limiting step,
so that this is formally an E1 elimination of toluene2 as shown
in Scheme 1. An interest in the relationships between structure
J. Chem. Soc., Perkin Trans. 2, 1997
1585

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Scheme 2 Preparations of 1,2-diphenylcycloalkanols, their linear isomers (n = 2–5) and 3,4-diphenylhexan-3-ols (THF = tetrahydrofuran)
with this stereochemical assignment, but was hardly conclu-
sive8 even in the cyclohexanol case, of necessity being based
almost entirely on the couplings to methine hydrogen. Fortu-
nately, all the isolated alcohols were nicely crystalline, and their
structures, discussed below, were confirmed as trans-1,2-
diphenylcycloalkanols by X-ray crystallography. The isotopic-
ally labelled compounds, [2,5,5-2H2]-5, [2,6,6-2H3]-6, [2,7,7-
2H3]-7 and [2,8,8-2H3]-8, were available by exchange with basic
D2O at the ketone stage, and authentic samples of the expected
product ketones were also prepared as shown. Coupling of
propiophenone and 1-phenylpropyllithium yielded both iso-
mers of 3,4-diphenylhexan-3-ol, one of which crystallised and
was shown by X-ray crystallography to be the erythro-isomer.
Crystallographic studies were undertaken, in the first
instance, to secure the structural assignments made in the
course of the preparative chemistry, but we comment briefly on
the features of each structure.
gen bond. Rather, asymmetric units are hydrogen bonded
together [intermolecular d(O ؒ ؒ ؒ O) = 2.912 Å]. The molecular
conformations differ only in minor details and again we depict
only one of the molecules in the unit (see Fig. 1). The cyclo-
heptanol ring adopts a distorted chair conformation with the
atoms C2, C3, C6 and C7 lying within 0.08 Å of their mean plane.
Atoms C4 and C5 lie 1.18 and 0.94 Å below this plane, and the
point atom, C1, carrying the axial hydroxy group, lies 0.567 Å
above it. The trans-phenyl groups occupy ‘equatorial’ positions
on the ring. Dihedral angles from the C2 methine to hydrogens at
adjacent methylene are 12 and 99Њ, and observed coupling con-
stants are J 11.5 and 2.0 Hz in the solution 1H NMR spectrum.
The crystal structure of 1,2-diphenylcyclooctanol contains
centrosymmetric hydrogen-bonded dimers [d(O ؒ ؒ ؒ O) = 2.935
Å]. In the molecule, the eight-membered ring adopts a near
ideal boat–chair conformation with (ignoring the substitution)
a plane of pseudo-symmetry running through C1 and C5. This
places the ‘in’ hydrogens at C3 and C7 in van der Waals contact
[d(H7A ؒ ؒ ؒ H3A) = 1.96 Å]. The hydroxy group then occupies
the ‘axial’ position at the point of the chair, and the phenyl
substituents equatorial on this chair portion. Dihedral angles to
the methine hydrogen at C2 are 25 and 83Њ, and these are con-
sistent with the observation of a doublet (J 7.7) as the signal
The asymmetric unit in the crystal structure of 1,2-
diphenylcyclopentanol contains two non-equivalent molecules
linked by a hydrogen bond [intermolecular d(O ؒ ؒ ؒ O) = 2.961
Å]. Molecular conformations differ only in minor detail and we
show only one of the molecules in the unit (see Fig. 1). The five-
membered ring adopts a distorted envelope conformation, with
a C1C3–C4C5 torsion angle of only Ϫ8.1Њ, so that these four
atoms are within 0.06 Å of their mean plane. The fifth ring
atom, C2, lies 0.63 Å out of this plane and forms the point of
the ‘flap’ of the envelope. The phenyls are attached at C1 and
C2, such that C1-phenyl has a near perfect gauche relationship
to the hydroxy and phenyl at C2. One of the cyclopentanols
shows a notably long bond (1.562 Å) between phenylated ring
carbons. Dihedral angles from the C2 methine hydrogen to
hydrogens of the adjacent methylene are 48 and 169Њ, consistent
with the doublets of doublets (J 7.5 and 11.5 Hz) observed in
1
from this hydrogen in the solution H NMR spectrum. The
C1᎐C2 bond linking the phenylated carbons is long (1.566 Å).
Disorder was again present in the structure of 3,4-diphenyl-
hexan-3-ol, and OH sites at hydroxys and the hydrogen at the
adjacent central carbon were given occupancies of 0.5 to fit the
requirements of space group No. 14 in which the molecule has a
centre of symmetry. Two molecules form a hydrogen-bonded
dimer and the crystal lattice is stabilised by hydrogen bonding
interactions to an adjacent asymmetric unit. Despite the dis-
order, the erythro relationship is clearly established, and within
the molecules the pairs of phenyl groups and of ethyl groups
are fully staggered.
In favourable cases, structures of series of reactive molecules
determined in this way have shown unusual bond lengths or
angles interpretable as distortions along a reaction coordinate.9
In the expected reactions, the C1᎐C2 bonds are to be cleaved
and the alcohol residue at C1 is transformed to a carbonyl.
Structural modifications along the ring-opening reaction co-
ordinate might therefore be lengthened C1᎐C2 bonds, short-
ened C1᎐O bonds, and angular distortions indicating sp3 to sp2
rehybridisation at C1. We have examined bond lengths and
angles at these atoms (Table 1), and can find no link between any
of the geometric parameters, or between any parameter set and
ring size. Neither, as will be seen later, is there any relationship
between reactivity of alkoxides and the parameters.
1
the solution H NMR spectrum of this compound.
The crystal structure of 1,2-diphenylcyclohexanol is dis-
ordered, with the hydroxy having an occupancy of 62.2% on C1
and 37.8% on C2 by occupancy refinement. Intermolecular
hydrogen bonding occurs from a hydroxy group in one mole-
cule either to the hydroxy or a phenyl group of a second. Never-
theless, the structure is clearly established as that of trans-1,2-
diphenylcyclohexanol, with the chair cyclohexane ring carrying
two equatorial phenyls and an axial hydroxy group. Dihedral
angles between the C2-methine hydrogen and adjacent meth-
ylenes are 179 and 62Њ, consistent with the observed couplings
of J 13.0 and 3.5 Hz.
As with the cyclopentanol, the crystal structure of 1,2-
diphenylcycloheptanol has an asymmetric unit containing two
non-equivalent molecules, but these are not linked by a hydro-
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J. Chem. Soc., Perkin Trans. 2, 1997

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Fig. 1 X-Ray crystal structures of 1,2-diphenylcycloalkanols
Table 1 Some angles and distance at bonds at reacting atoms in the X-ray crystal structures of the tertiary-alcohols
Molecule
r(C1᎐C2)/Å
r(C1᎐O)/Å
φ(Ph᎐C1᎐C2᎐Ph)/Њ
θ(O᎐C1᎐Ph)/Њ
erythro-3,4-Diphenylhexanol
Cyclopentanol(mol A)
Cyclopentanol(mol B)
Cyclohexanol
Cycloheptanol(mol A)
Cycloheptanol (mol B)
Cyclooctanol
1.563
1.54
180
322.9
111.4
107.7
110.0
110.1
110.0
110.5
1.545(9)
1.562(9)
1.555(3)
1.563(4)
1.559(4)
1.566(3)
1.421(6)
1.422(7)
1.451
1.442(4)
1.431(4)
1.440(2)
66.7
66.7
55.8
62.8
55.2
53.5
Molecular mechanics calculations, using the MM3 empirical
forcefield 10 as implemented in MACROMODEL 4.511
(MM3*), were carried out on all the trans-1,2-diphenylcyclo-
alkanols using full conformational searches, which found global
minimum energy conformations corresponding closely to those
in the crystal structures. Table 2 summarises the results of the
EFF calculations on the cycloalkanols, and on both threo- and
erythro-3,4-diphenylhexan-3-ol. The bracketed values in the
first column are steric energy differences between the global
minimum and the next lowest conformation of each alkanol.
These differences range from 8.22 kcal molϪ1 (1 cal = 4.184 J)
for the cyclohexanol (where the second conformation is a twist
boat conformation) to 5.54 kcal molϪ1 for the cyclopentanol
(where the second conformation corresponds to a pseudo-
rotation which places the hydroxylated carbon at the point of
the flap of an envelope). The calculations thus suggest that the
trans-1,2-diphenyl groups are effective conformational locking
groups for the cycloalkanols. Even for the cyclopentanol, the
population of the second conformation will be less than 0.01%
at normal temperatures. For the acyclics, in the threo-isomer the
three conformations by rotation about the C3᎐C4 bond are
within 0.1 kcal molϪ1 of each other; in the erythro isomer, the
conformation with fully staggered phenyl and ethyl groups is
favoured over all others, but only by 1.07 kcal molϪ1.
that there are appropriate group or bond energy increments to
add to the steric energies. Heats of isomerisation would there-
fore be obtained by taking the difference in steric energies of the
cyclic and linear isomers, added to a correction involving
increments for those groups involved in the bonding changes in
the ring opening, which is constant in the series of molecules
examined in this work. Differences in steric energies alone then
should accurately reflect differences in heats of isomerisation
for the series. The products of isomerisation may be regarded as
the 1,5-, 1,6-, 1,7- or 1,8-diphenylalkanones, or their enols, and
Table 2 also contains steric energies obtained for these products
in their fully extended conformation. The second and third col-
umns present steric energy differences between ground state
conformation of the alcohols and ketone or Z-enol isomers. In
both cases, these increase in the order: cyclohexanol ≈
acyclics < cycloheptanol < cyclopentanol < cyclooctanol <
cyclobutanol, and this is the expected reactivity ordering in
reactions in which strain relief is dominant in transition state
formation. For the ketones, differences range from 4.22 kcal
molϪ1 for the cyclohexanol, to 18.69 kcal molϪ1 for the cyclo-
octanol, with a difference in strain release of 14.47 kcal molϪ1.
There are good qualitative indications that steric effects are
important in alkoxide decompositions,13,14 and correlations
between strain relief, calculated by empirical forcefield methods,
and reactivity in fragmentation of sets of sterically congested
acyclic lithium tertiary-alkoxides in hexamethylphosphoric tri-
amide (HMPA) have been described by Lomas and Dubois.15 If
steric energy release were fully expressed in the same way in the
1,2-diphenylcycloalkanols, then the reactivity range would be
very large with cyclooctanol expected to be ca. 1010 more
reactive than the cyclohexanol.
These calculations provide a basis for comparing the strain
released in the expected ring openings. Strain in organic mole-
cules is an enthalpy measured by comparing their heats of
formation with those estimated for a ‘strain free’ model con-
structed using bond or group increments based on thermo-
chemical data of an agreed set of ‘strain free’ molecules.12 Heats
of formation can be obtained from EFF calculations, provided
J. Chem. Soc., Perkin Trans. 2, 1997
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Table 2 Steric energies for tertiary alcohols and their acyclic isomers from MM3* empirical forcefield calculationsa
Compounds
Esteric /kcal molϪ1
∆Es(Z-enol)/kcal molϪ1
∆Es (ketone)/kcal molϪ1
trans-1.2-Diphenylcyclobutanol
1,4-Diphenylbutan-1-one
43.06 (3.73)
17.36
14.90
32.86 (5.54)
19.06
13.80
28.16
25.70
13.80
4.22
(Z)-1,4-Diphenylbut-1-en-1-ol
trans-1,2-Diphenylcyclopentanol
1,5-Diphenylpentan-1-one
(Z)-1,5-Diphenylpent-1-en-1-ol
trans-1,2-Diphenylcyclohexanol
1,6-Diphenylhexan-1-one
19.06
8.83
24.85 (8.22)
20.62
(Z)-1,6-Diphenylhex-1-en-1-ol
trans-1,2-Diphenylcycloheptanol
1,7-Diphenylheptan-1-one
(Z)-1,7-Diphenylhept-1-en-1-ol
trans-1,2-Diphenylcyclooctanol
1,8-Diphenyloctan-1-one
16.01
34.49 (6.66)
21.47
16.68
41.49 (6.53)
22.80
17.41
23.45
13.02
18.69
(Z)-1,8-Diphenyloct-1-en-1-ol
threo-3,4-Diphenylhexanol
erythro-3,4-Diphenylhexanol
1-Phenylpropan-1-one
18.04
26.36 (0.02)
24.46 (1.07)
11.88
10.35
8.45
7.46
5.56
(Z)-1-Phenylprop-1-en-1-ol
1-Phenylpropane
8.99
7.02
a
1 cal = 4.184 J.
differences in reactivity of ‘free’ and ‘paired’ alkoxides in their
fragmentation or ring openings. The reaction scheme given
by eqns. (1)–(3), with ion pairing constants (Kass) in DMSO
Reactivity studies
These normal and medium ring cycloalkanols were stable to the
aqueous basic conditions which induce ring openings in the
cyclobutanols and cyclopropanols. Reactions were therefore
examined in more strongly basic media used earlier in studies of
cleavages of 1,2,3-triphenylpropanols. Initially, each alcohol
was treated separately with excess dimsylsodium in DMSO
solution at 40 ЊC, completely converting the alcohol to its
alkoxide.16 Attempts to monitor formation of ketone enolate
UV-spectrophotometrically were not successful, and sampling
methods were therefore adopted. Aliquots of the reaction
mixture were periodically withdrawn, quenched with dilute
aqueous acid, and then analysed by GLC. These studies estab-
lished that the anticipated isomerisations to the linear ketones,
identified by GC–MS comparison with the authentic samples,
occurred under these conditions. Provided oxygen was rigor-
ously excluded, these ketones were the sole products of reaction
after dilute aqueous acidic quench. If oxygen was not excluded,
then a variety of products arising from oxidation of the ketone
enolate were formed.
Kass
ROϪ ϩ Mϩ
ROϪ
ROϪMϩ
(1)
(2)
(3)
kfree
P
P
kip
ROϪMϩ
ranging from 10 (for M = K) to 104 (for M = Li), and kfree ӷ kip,
has been shown to describe the behaviour of the alkoxides of
1,2,3-triphenylpropan-2-ol, and is expected to apply here also.
Under these circumstances, the reaction velocity is given by
eqn. (4) where c = [ROϪ] ϩ [ROϪMϩ]. Pseudo-first-order rate
v = [kfree /(Kass[Mϩ])]c
(4)
Disappearances of the alcohol for the relatively fast reactions
of 7, 8 and 9 showed good first order behaviour over at least
three half-lives. For the cyclohexanols, reaction was very slow
and it was only practical to observe them to ca. 20% conversion
which required nearly 72 h at 50 ЊC with dimsyl potassium in
DMSO. The disappearance of the cyclohexanol was fitted to a
first-order decay. For the cyclopentanol reactions which showed
rates between those of the cyclohexanol and the faster reacting
group, first order behaviour was also obtained, but small add-
itional peaks (always <3% of the trans-1,2-diphenylcyclo-
pentanol), with retention times close to those of trans-1,2-
diphenyl-cyclopentanol, were observed in the GLC of the reac-
tion mixtures early in the course of the reaction monitoring.
These peaks showed identical MS fragmentations patterns to
the trans-1,2-diphenylcyclopentanol, and we assign them to
small amounts of transiently formed cis-1,2-diphenylcyclo-
pentanol, which is indicated by molecular mechanics calcu-
lation to be 1.7 kcal molϪ1 less stable than the trans isomer. For
the six-, seven- and eight-membered ring 1,2-diphenylcyclo-
alkanols, cis-isomers are calculated to be >4 kcal molϪ1 more
strained than the trans-isomers.
constants (kobs = kfree /Kass[Mϩ]) for product formation thus
depend on both metal ion concentration and Kass. For this series
of structurally similar alkoxides, we assume that association
constants for ion-pair formation with a particular metal are not
strongly structure dependent. For reactions of two or more
alcohols in the same metal dimsyl solution, the nature of the
metal ion and metal ion concentrations are identical, and
experimentally determined relative rates then reflect relative
magnitudes of kfree for the alkoxides involved. This approach
allows use of the ion-pairing constants with different metals to
adjust experimental reactivities to conveniently observable
values, and the rate data are collected in Table 3. Thus, for the
more reactive alcohols (the acyclics, cyclooctanol and cyclo-
heptanol) use of dimsyllithium solution gave rates which were
convenient for sampling and analysis. Reactions were con-
ducted at two different temperatures, and relative reactivities at
18 and 35 ЊC are the same. The cyclooctanol–cycloheptanol
pair were also examined in 1,3-diaminopropane (DAP) with its
potassium salt as base (DAP–KAPA),18 and the constancy of
the cyclooctanol–cycloheptanol rate ratio in two different
solvent–base systems provides some support for this approach
to the construction of a scale of reactivities. For the less reactive
alcohols (cyclohexanol and cyclopentanol), dimsylpotassium
was used, but even so higher temperatures were necessary to
permit the cyclohexanol fragmentation to be observed. Overlap
between the extremes of reactivity was made by simultaneous
These experiments established approximate relative reactivi-
ties with the cyclooctanol being more than 105 times more
reactive than the cyclohexanol. Construction of a more accur-
ate scale of alkoxide reactivities is complicated by ion-pair
formation of alkali metal alkoxides in DMSO,17 and the large
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Table 3 Rate data for base induced isomerisations of 1,2-diphenylcycloalkanols and for cleavage of 3,4-diphenylhexan-3-ols
Substrate sets
Solvent/base
T/ ЊC
30
kobs /sϪ1
Rate ratio
Cyclooctanol
Cycloheptanol
Cyclooctanol
Cycloheptanol
Cyclopentanol
Cycloheptanol
Cyclopentanol
Cycloheptanol
Cyclopentanol
Cycloheptanol
Cyclopentanol
Cycloheptanol
erythro-Hexanol
threo-Hexanol
Cyclooctanol
Cycloheptanol
erythro-Hexanol
threo-Hexanol
Cyclooctanol
Cycloheptanol
KAPA–DAP
1.13 (±0.07) × 10Ϫ3
9.81 (±0.40) × 10Ϫ6
1.29 (±0.03) × 10Ϫ2
1.24 (±0.11) × 10Ϫ4
6.16 (±0.48) × 10Ϫ6
4.97 (±0.17) × 10Ϫ3
7.34 (±0.48) × 10Ϫ6
5.54 (±0.17) × 10Ϫ3
2.65 (±0.10) × 10Ϫ5
1.04 (±0.05) × 10Ϫ6
2.38 (±0.13) × 10Ϫ5
1.66 (±0.25) × 10Ϫ6
3.05 (±0.21) × 10Ϫ6
1.15 (±0.17) × 10Ϫ5
4.09 (±0.44) × 10Ϫ5
3.97 (±0.52) × 10Ϫ7
3.54 (±0.24) × 10Ϫ5
1.11 (±0.17) × 10Ϫ4
3.58 (±0.66) × 10Ϫ4
3.17 (±0.11) × 10Ϫ6
k8 /k7 = 115
k8 /k7 = 104
k7 k5 = 807
k7 /k5 = 754
k5 /k6 = 25.5
k5 /k6 = 14.3
kth /ker = 3.77
KAPA–DAP
50
K dimsyl–DMSO
K dimsyl–DMSO
K dimsyl–DMSO
K dimsyl–DMSO
Li dimsyl–DMSO
30
40
50
50
18
k8 /kth = 3.55
k8 /k7 = 113
kth /ker = 3.13
Li dimsyl–DMSO
35
k8 /kth = 3.22
k8 /k7 = 103
reaction of cyclopentanol and cycloheptanol, and for this pair,
the reactivity difference was largest.
0.411∆Grel Ϫ 9.543 with r2 = 0.801). Even so, the fit is not a
particularly good one, and can be improved by using a smaller
contribution for entropy increase (ca. 2.5 cal KϪ1 molϪ1) for
each single bond lying between the reacting atoms, suggest-
ing that free rotation about these bonds is not achieved in the
transition states. Dispersion may arise also from variation in
transition structure with differing extents of carbon–carbon
bond cleavage for each ring size, or a change in rate-
determining step within the series of compounds from carbon–
carbon bond cleavage to rate-limiting proton transfer, and
indeed, observations of trans–cis isomerism accompanying the
ring opening of the cyclopentanol are consistent with rate-
limiting proton transfer in this case. Variation of product label-
ling patterns in ring openings of the deuteriated cycloalkanols,
[2H3]-5, [2H3]-6, [2H3]-7 and [2H3]-8 supports such mechanistic
differences.
Attempts to place the reactivity for the ring opening of 1,2-
diphenylcyclobutanol on the same scale by using a paired reac-
tion with 1,2-diphenylcyclooctanol with dimsyllithium as base
were not successful. At the lowest possible temperature (ca.
18 ЊC), ring opening of the cyclobutanol was complete before
the first sample could be extracted and quenched (ca. 30 s). We
can only estimate that the cyclobutanol is >100 times more
reactive than the cyclooctanol.
The combined rate measurements permit the construction of
a ladder of reactivities for this set of compounds, contained in
Table 4, and scaled relative to that of erythro-3,4-diphenyl-
hexan-3-ol. The span of reactivities is greater than 106, and for
the cycloalkanols, rates increase with increasing steric energy of
the cycloalkanol. However, as shown in Fig. 2(a), values of log
krel correlate poorly with ∆Esteric for isomerisation of cyclo-
alkanols to the acyclic ketones. For the ketone steric
For the 3,4-diphenylhexanols (whose reactivity is very close
to that found in earlier work for 1,2,3-triphenylpropanol1) the
rate ratio kthreo /kerythro should reflect differences in steric energy
release, with little contribution from differential entropy
change. The molecular mechanics calculations show that the
threo compound is 1.9 kcal molϪ1 more strained than its erythro
energy data, the best straight line is given by log krel
=
0.397∆Esteric Ϫ 7.154 (r2 = 0.724). Use of steric energy differ-
ences for isomerisations to the enols does not improve the
correlation. Notably, the acyclic hexanols are >105 times more
reactive than the cyclohexanol, despite showing similar release
of steric energy on cleavage of benzylic bonds.
isomer, and full expression of this difference would give kthreo
/
kerythro ca. 24, while the experimental value is ca. 3.5, suggesting
that strain release is far from complete in the rate-limiting step
which, our earlier studies2 on closely related 1,2,3-triphenyl-
propanol suggest is carbon–carbon bond cleavage to yield the
ketone–benzylic carbanion complex.
Such behaviour is not entirely unexpected since these steric
energy differences take no account of the entropy changes
accompanying ring-opening or fragmentation. Release of the
constraints on rotation about single bonds in ring-openings has
been estimated 19 to contribute an entropy increase of ca. 4 cal
KϪ1 molϪ1 for each single bond lying between the reaction
atoms. At 300 K, this would reduce free energies of isomeris-
ation by 4.8, 6.0, 7.2 and 8.4 kcal molϪ1 respectively for five-,
six-, seven- and eight-membered rings. In the cleavage of the
linear models, an entropy change associated with the three add-
itional translational and rotational degrees of freedom in the
production of two molecules from one, must be taken into
account. For standard states of 1  in solute, at 25 ЊC, this
has been estimated to be as much as 50 cal KϪ1 molϪ1, or 15
kcal molϪ1 in the free energy of the cleavage reaction at 300 K.
Addition of these entropic corrections to the estimates of
enthalpic strain release produces a crude measure of the relative
free energy change (∆Grel) in the isomerisations or cleavages,
and these estimates are also included in Table 4. Fig. 2(b)
shows a plot of log krel against these values for ∆Grel for
ketone formations, and it is clear that inclusion of the
entropic factors moves all points, including those from the
Labelling studies and kinetic isotope effects
For ring-openings of triply deuteriated 1,2-diphenylcyclo-
alkanols in [1H6]DMSO, the possible product labelling patterns
are shown in Scheme 3. Ring opening, and protonation of the
benzylic carbanion by DMSO (pKa = 33), should yield, after
quench, doubly deuteriated ketone. Ring-opening and intra-
molecular transfer of a relatively acidic (pKa ca. 25) C2-
deuteron 16 to the benzylic carbon should, after quenching of the
enolate, yield triply deuteriated ketone. Because exchange at the
enolizeable positions is not fully controlled under the quench
conditions, the isolated ketones were treated with aqueous
potassium carbonate, conditions known to exchange hydrogens
at these positions, but not the benzylic positions. Ring cleavages
involving external and internal proton transfers would thus
yield, finally, [2H1]- and [2H2]-ketones, respectively, with the
deuterium incorporated at the benzylic positions. Interpret-
ation of the product labelling patterns, however, is complicated
linear models, closer to a single correlation line (log krel
=
J. Chem. Soc., Perkin Trans. 2, 1997
1589

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Table 4 Relative reactivities in ring opening reactions of diphenylcycloalkanols or fragmentations of 3,4-diphenylhexanols, steric energy release for
ketone formation, and estimated relative free energy changes for isomerisations
Diphenylalkanol
krel
log krel
Ϫ5.15
0.00
0.54
Ϫ0.96
Ϫ3.85
1.07
∆Esteric /kcal molϪ1
∆Grel at 300 K/kcal molϪ1
Cyclohexanol
7.1 × 10Ϫ6
1.0
4.22
5.56
7.46
13.02
13.80
18.69
10.22
20.56
22.46
20.22
18.60
27.09
erythro-Hexan-3-ol
threo-Hexan-3-ol
Cycloheptanol
Cyclopentanol
Cyclooctanol
3.5
1.1 × 10Ϫ1
1.4 × 10Ϫ4
1.2 × 101
Fig. 2 Plots of log krel against steric energy release in ketone formation (a), or against steric energy release with entropic corrections (b). Lines are
best straight lines for the cycloalkanol data only. In (a), log krel = 0.397∆Es Ϫ 7.154 (r2 = 0.724); in (b) log krel = 0.378∆Grel Ϫ 9.422 (r2 = 0.872).
Scheme 3 Fate of isotopic labels in reactions of [2H3]-1,2-diphenylcyclopentanol, [2H3]-1,2-diphenylcycloheptanol and [2H3]-1,2-diphenyl-
cyclooctanol, and associated kinetic hydrogen isotope effects
by a superimposed exchange of deuterium at benzylic positions
with DMSO in these strongly basic solutions. These could occur
either in the cycloalkanol,20 or more probably in the product,
to reduce deuterium incorporations at benzylic positions, so
that measured incorporations will always represent lower limits
for those from the competing proton transfers which follow the
ring-opening. Rates of exchange at benzylic positions have been
measured for toluene, ethylbenzene and cumene21 with 0.56 
KOBut in DMSO at 30 ЊC, and half-lives for exchange are
43 min, 3 h and 30 h respectively. It is likely therefore, that
reactions of the cyclooctanol using dimsylsodium and cyclo-
heptanol using dimsylpotassium, which are complete in less
than 10 min at T < 30 ЊC, are fast enough for the contribution
of solvent exchange at the benzylic position to be small, and
comparable with the uncertainties in the measurement of the
incorporations (± ca. 3%). For the cyclopentanols, which
require ca. 2 h at 50 ЊC even with dimsylpotassium, the contri-
bution is expected to be significant, and for the very slowly
reacting cyclohexanol, uncertainties arising from benzylic
exchange completely undermine the usefulness of an experi-
ment with this alcohol.
The results of experiments with [2H3]-5, [2H3]-7 and [2H3]-8
are shown in Scheme 3. Deuterium incorporations are from
measurements of parent ion peak ratios in the EI mass spectra
of the ketones. These fragment to yield benzyl cations (ca. 30%)
and analysis of peak ratios at m/z = 91, 92 and 93 confirmed
that the residual deuterium was incorporated at the benzylic
positions.
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J. Chem. Soc., Perkin Trans. 2, 1997

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Fig. 3 Mechanisms and reaction profiles for ring opening reactions
The results are consistent with the polar mechanism but the
Experimental section) suggests that this is not a major source of
deuterium incorporations show a clear distinction between the
cyclooctanol ring opening and those of the cyclopentanol
and cycloheptanol. Formation of >95% of 8-deuterio-1,8-
diphenyloctanone indicates protonation of the intermediate
carbanion by DMSO, despite the availability of a more acidic
intramolecular proton source. The same situation was found 1
in the cleavage of the acyclic 1,2,3-triphenylpropanol, 1, also
in DMSO. Less surprisingly perhaps, ring openings of the
small ring 1,2-diphenylcycloalkanols, 35 and 4,6 in deuteriated
aqueous medium also yielded products in which the intermedi-
ate benzylic carbanions were protonated by solvent. For the
cycloheptanol, and cyclopentanol, the isolation of 57 and 35%
of [2H2]ketones, respectively, indicates important amounts of
deuteron transfer from the ketone α-carbons (Cn to C2), pre-
sumably intramolecularly, and in view of the solvent exchange
discussed above, that process in the cyclopentanol is probably
the major reaction pathway.
error, even in the cyclopentanol reaction.
We again discuss these effects within the framework of initial
carbon–carbon cleavage to yield a transient benzylic carbanion,
followed by proton transfers to yield the enolate of the acyclic
ketone. In the event that the initial carbon–carbon bond cleav-
age is rate limiting (TS1 in Fig. 3), then the major contribution
to the observed rate ratio should be a secondary α-deuterium
isotope effect associated with the hydron at the benzylic posi-
tion. Labels at the methylene position seem too remote from the
reaction site for their bonds to be strongly perturbed. At the
benzylic position, the carbon atom would be undergoing an sp3
to sp2 rehybridisation, and, theoretically, values up to 1.4 per D
could be attributed to such secondary isotope effects.23 Values
of between 1.2 and 1.3 per D have been observed in other reac-
tions where benzylic2 or allylic24 carbanions have been formed.
These large secondary isotope effects are associated with bend-
ing frequencies at allylic anionic (and presumably also at
benzylic) centres which are substantially lower even than
those at an ordinary olefinic C᎐H bond.25 The values reported
in Scheme 3 for the cyclooctanol and cycloheptanol are
at the extreme end of the range of plausible values for second-
ary effects. Those for the cyclopentanol are clearly outside
that range, and must contain a contribution from an isotope
effect on one of three possible subsequent proton transfer
steps.
If a proton is transferred from DMSO to the benzylic car-
banion (not shown in Fig. 3), any isotope effect on that step
would be associated with the α-deuterium at that site and rehy-
bridisation of the carbon from sp2 to sp3. This is expected to be
small and inverse. Because of the exothermicity of the proton
transfers, it is unlikely that any subsequent proton transfers to
yield the final product could be rate limiting, and the overall
kinetic isotope effect for rate-limiting protonation of the
benzylic carbanion by DMSO should be a combination of the
secondary α-deuterium effect on carbanion formation, and the
inverse secondary effect on its protonation yielding an effect
rather smaller than that found in any of the reactions studied.
The experimental data thus suggest that this pathway is not
followed for any of the ring openings.
The kinetic isotope effects (kie values) associated with the
labelling were measured by monitoring the time course of the
composition of a mixture of labelled and unlabelled cyclo-
alkanols reacting in the same DMSO–dimsyl solution. The
composition changes are related 22 to the kie by the relation-
ship in eqn. (5), where xH and xD are the mole fractions of
0
0
ln[α(xH /xH )]
0
(5)
kie =
ln[α(xD /xD )]
0
unlabelled (2H0) and labelled (2H3) alcohol at initial time, and
xH and xD are the mole fractions of unlabelled and labelled
alcohol at time when α is the fraction of unreacted alcohol. The
results of kie measurements are also collected in Scheme 3.
Average values of 2.47, 1.37 and 1.43 are obtained for cyclopen-
tanol, cycloheptanol and cyclooctanol, respectively. Uncertain-
ties quoted are the standard deviations of a number of meas-
urements taken throughout the reactions. Base catalysed
exchange at the benzylic sites in the cycloalkanols will mean
that the true kie values should be always greater than those
obtained from the relationship using experimentally deter-
mined label incorporations, but the consistency of the data (see
J. Chem. Soc., Perkin Trans. 2, 1997
1591

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In the second of these, a hydron may be abstracted by dimsyl
anion from the methylene adjacent to the carbonyl, yielding a
dianion (via TS2a in Fig. 3). This is also carbon-to-carbon pro-
ton transfer, expected to be strongly exoergic on the basis of the
relative pKa values16 of DMSO and acetophenone. In such a
proton transfer, primary kinetic effects are expected to be much
reduced from their Westheimer maximum of ca. 7.26 Because of
the labelling pattern, there will be a secondary α-deuterium
effect from rehybridisation of the methylene carbon. Again,
since this proton transfer is so strongly exoergic, it is extremely
unlikely that a second exoergic proton transfer required to
complete the reaction could be rate limiting.
The final possibility is that there may be an intramolecular
transfer of hydron from the methylene to the benzylic anion (via
TS2b in Fig. 3) to yield the product enolate directly. This is
also a carbon-to-carbon proton transfer, which should be even
more exoergic than the second possibility. Again, there will be
secondary effects associated with rehybridisation at proton
donating and proton accepting sites. Since these effectively
exchange their hybridisations, it can be expected that the net
secondary contributions will be small.
If either of these proton transfers were rate limiting, then the
overall rate ratio should be the product of the secondary α-
deuterium effect on the formation of the benzylic carbanion,
and the contribution on transfer of the hydron at the methylene
adjacent to the carbonyl to either dimsyl or benzylic carbanion.
For the cyclooctanol reaction, product labelling patterns permit
only the proton transfer via TS2a, but the observed rate ratio
(kie = 1.43) suggests that its contribution is not large, and we
suggest that carbanion formation is rate limiting, a situation
resembling that proposed for cleavage of the acyclic compound
1,2,3-triphenylpropanol.2 For the cycloheptanol reaction, the
product labelling experiments permit reaction pathways by
both TS2a and TS2b, but again, the size of the kie suggests that
the carbanion formation is rate limiting. For the cyclopentanol
reaction the observed ratio is large enough to reflect an equi-
librium secondary effect (ca. 1.3) on a reversible ring opening
(TS1) and rate-limiting proton transfers via both TS2a and
TS2b with kie values of ca. 1.9, which would not be unreason-
able for these strongly exoergic proton transfers.27
a range of solvents, all distilled before use, were used in column
chromatography. Light petroleum refers to the fraction of bp
40–60 ЊC. IR spectra were recorded on a Perkin-Elmer 1710-FT
spectrometer, routinely on thin films on NaCl plates. UV
spectra were recorded on a Shimadzu UV-260 spectrometer on
1
solutions in 95% aqueous ethanol. Routine H NMR spectra
were run on a Bruker AC 300E spectrometer operating at 300
MHz or a Gemini running at 200 MHz. 13C NMR spectra were
run on the Bruker AC 300E spectrometer at 75 MHz. Chemical
shifts are reported in ppm (δ) relative to internal SiMe4. J values
are in Hz. Signal splittings are reported as: singlet (s), doublet
(d), triplet (t), quartet (q), doublet of doublet (dd), doublet of
doublet of doublet (ddd), triplet of doublet (td) and multiplet
(m). Routine mass spectra were run on a Fisons VG Trio 2000
spectrometer using electron impact ionisation at 70 eV or chem-
ical ionisation with ammonia as the reagent gas. Negative Cl
mass spectra were run on a Kratos Concept LS1; the GC–MS
were run on a Perkin-Elmer Sigma 3 GLC in conjunction with
the Kratos MS 25 mass spectrometer. Deuterium incorpor-
ations were calculated by solving the equations given by
Biemann,28 using a computer program written in BASIC for
the BBC Micro. Melting points were determined on a Kofler
hot stage microscope and are uncorrected. All microanalyses
were carried out at the University of Manchester Micro-
analytical Laboratories under the direction of Mr M. Hart.
X-Ray crystal structures were determined by Mr R. Beddoes
at the X-ray crystallographic service at the University of
Manchester.
2-Phenyl-2,n,n-trideuteriocycloalkanones
These were prepared by potassium carbonate catalysed
exchange of 2-phenylcycloalkanones with D2O in dioxane fol-
lowing a published procedure.6 For [2H3]-5, mass spectrometric
2
2
analysis (positive Cl) gave incorporation: H2 10.6 ± 0.1%, H3
89.1 ± 0.1%; for [2H3]-6 2H2 10.1 ± 0.1%, 2H3 89.6 ± 0.1%;
[2H3]-7: H1 1.2 ± 0.1%, H2 6.6 ± 0.1% and H3 92.2 ± 0.1%;
2
2
2
and [2H3]-8: 2H1 0.6 ± 0.1%, 2H2 10.6 ± 0.1%, 2H3 88.5 ± 0.1%.
trans-1,2-Diphenylcyclopentanol, 5, and 1,2-diphenyl-2,5,5-tri-
deuteriocyclopentanol, [2H3]
2-Phenylcyclopentanone (3.55 g, 22 mmol) in 30 ml of dry
diethyl ether was added slowly to phenyllithium (30 ml of 0.8 
solution in diethyl ether) and allowed to react for 2 h. The
mixture was then poured into 60 ml of cold 1  HCl solution
before separation of the ether layer and further extraction
and drying (MgSO4). Evaporation yielded an oil which was
chromatographed on silica (light petroleum–diethyl ether sol-
vent gradient). The alcohol crystallised from the main fraction
and recrystallisation from light petroleum gave white crystals;
mp 48–49 ЊC (Found: C, 85.7; H, 7.62. Calc. for C17H18O: C,
85.67; H, 7.61%); νmax/cmϪ1 (KBr) 3557, 1602, 1495, 1447, 1332,
1284, 1163 and 1018; δH (200 MHz; CDCl3) 1.62 (1H, s, OH),
1.88–2.55 (6H, m), 3.52 (1H, dd, Jcis 11.5 and Jtrans 7.5), 7 (2H,
m) and 7.14–7.4 (8H, M); δC(75 MHz; CDCl3) 22.74, 29.76,
43.25, 57.74, 83.94, 125.1, 126.46, 126.98, 128.03, 128.22,
128.85, 138.11 and 146.5; m/z (EI) 238 (Mϩ, 41), 220
([M Ϫ H2O]ϩ, 16), 133 (56), 120 (95), 105 (100), 91 (31) and 77
(37); (CI, NH3) 266 ([M ϩ 2NH4]ϩ, 2), 256 ([M ϩ NH4]ϩ, 25),
238 (Mϩ or [M Ϫ H2O ϩ NH4]ϩ, 100), 221 ([M Ϫ OH]ϩ or
[M Ϫ H2O ϩ H]ϩ, 87), 105 (7) and 91 (2).
Conclusion
The behaviour of these alkoxides has illustrated almost all the
possible complexities that can arise in structure–reactivity
relationships, even when compounds with closely similar react-
ing groups are compared. Qualitative free energy profiles of the
cyclooctanol, cycloheptanol and cyclopentanol ring openings,
consistent with the available data are also presented in Fig. 3. In
constructing them, we have assumed that the intermediate car-
banions, I1, are of similar energy and that barriers to inter-
molecular proton transfer, via TS2b (solid line), are not
strongly dependent on ring size. The intramolecular proton
transfers, however, occur through cyclic arrays of the same size
(on an atom for atom basis) as those for ring closures, and
barriers for both are expected to vary in response to the
entropic and enthalpic factors discussed earlier, but not with
exactly the same sensitivity. Barriers to ring closure decreasing
with ring size eventually result in reversible ring opening; and
barriers to intramolecular proton transfer decreasing with ring
size yield increasing amounts of the intramolecular proton
transfer products.
Reaction of 2-phenyl-2,5,5-trideuteriocyclopentanone simi-
larly yielded trans-1,2-diphenyl-2,5,5-trideuteriocyclopentanol
(60%); mp 48–49 ЊC (Found: C, 84.78; H, 7.62. Calc. for
C17H15D3O: C, 84.6; H, 7.51%). Mass spectrometric analysis
Experimental
2
2
(positive CI) gave incorporation: H1 4.6 ± 0.1%, H2 26.5 ±
0.1% and H3 68.8 ± 0.1%.
2
GLC was carried out on a Carlo Erba 4130 chromatograph
fitted with a capillary column (5 m × 0.22 mm) with a 0.25 µ
OV-1 cross-bonded stationary phase and hydrogen at 1 cm3
minϪ1 as carrier gas. Merck precoated silica plates (0.25 mm
Kieselgel 60 F254) were used for analytical TLC. Kieselgel H and
trans-1,2-Diphenylcyclohexanol, 6 and trans-1,2-diphenyl-2,6,6-
trideuteriocyclohexanol, [2H3]-6
These compounds were prepared by the literature methods29
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J. Chem. Soc., Perkin Trans. 2, 1997

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and had spectroscopic properties in full agreement with
reported data. The crystals had mp 66–67 ЊC (lit., 64–65 or 67–
69 ЊC) (Found: C, 85.4; H, 7.9. Calc. for C18H20O: C, 85.67; H,
7.98%).
naphthalene, 10.88 g, in THF, 50 ml) maintaining 25 > T >
27 ЊC. Excess of lithium–naphthalene was then destroyed by the
addition of a little methanol, before dilution with water, extrac-
tion with diethyl ether and drying (Na2SO4). Solvent evapor-
ation and bulb-to-bulb distillation (95–105 ЊC, 0.2 mmHg) gave
7.5 g of a colourless oil, which GLC analysis showed to be 1:1
mixture of isomers. The isomers were separated by chrom-
atography on silica (elution with 20% diethyl ether in light
petroleum) to give the threo-isomer (28%) as a colourless oil,
and the erythro-isomer (28%) as colourless crystals. The erythro-
isomer was then recrystallised from light petroleum and its
structure determined by X-ray crystallography.
Reaction of 2-phenyl-2,6,6-trideuteriocyclohexanone (1.8 g,
7 mmol) with phenylithium (0.8 g, 10 mmol) as described above
yielded trans-1,2-diphenyl-2,6,6-trideuteriocyclohexanol: mp
(hexane) 65–67 ЊC (Found: C, 84.72; H, 8. Calc. for C18H17D3O:
C, 84.65; H, 7.89%). Mass spectroscopy (positive CI) indicated
the following deuterium incorporation: 2H1 1.2 ± 0.1%, 2H2
2
6.3 ± 0.1% and H3 92.4 ± 0.1%.
trans-1,2-Diphenylcycloheptanol, 7, and 1,2-diphenyl-2,7,7-tri-
deuteriocycloheptanol, [2H3]-7
For threo-3,4-diphenylhexan-3-ol; νmax/cmϪ1 (NaCl) 3476,
3027, 2968, 1494, 1378 and 968; δH (200 MHz, CDCl3) 7.1–7.4
(8H, m), 6.95 (2H, m), 2.85 (1H, dd, J 12 and 3.7), 1.73–2.15
(4H, m), 1.6 (1H, s) and 0.6–0.8 (6H, m); m/z (EI) 237
([M Ϫ OH]ϩ, 90), 236 ([M Ϫ H2O]ϩ, 26), 207 (29), 167 (36), 135
(100), 91 (23) and 57 (50); m/z (positive CI, NH3) 272
([M ϩ NH4]ϩ, 6), 255 ([M ϩ 1]ϩ, 5), 254 (Mϩ, 25), 238 (28), 237
([M Ϫ OH]ϩ, 100), 135 (8).
Reaction of 2-phenylcycloheptanone (2.4 g, 12.6 mmol) with
phenyllithium (20 ml of a 0.8 molar solution, 16 mmol in THF)
at Ϫ15 ЊC yielded, after bulb-to-bulb distillation and chrom-
atography on silica (gradients of light petroleum–diethyl ether),
the alcohol (3.3 g, 91%) which was crystallised from light
petroleum (40–60), mp 57 ЊC (Found: C, 85.88; H, 8.73. Calc.
for C19H22O: C, 85.67; H, 8.32%); νmax/cmϪ1 (NaCl) 3562, 3027,
2928, 1601, 1493, 1297, 1070, 1050, 923; δH (200 MHz; CDCl3)
1.55–2.27 (10H, m), 2.36 (1H, m), 3.24 (1H, dd, J 11.5 and 2),
6.82 (2H, m) and 7–7.35 (8H, m, ArH); δC(75 MHz; CDCl3)
21.19, 28.19, 28.26, 29.51, 42.51, 57.1, 77.8, 124.59, 126.11,
126.14, 127.72, 127.77, 129.1, 143.23 and 149.75; m/z (EI) 266
(Mϩ, 18.3), 248 ([M Ϫ H2O]ϩ, 7.66), 144 (74), 133 (67), 120 (76),
105 (100) and 91 (28); (CI, NH3) 284 ([M ϩ NH4]ϩ, 6.7), 266
(Mϩ, 7), 249 ([M Ϫ OH]ϩ, 100).
For erythro-3,4-diphenylhexan-3-ol: mp 61.5–63.5 ЊC; νmax
/
cmϪ1 (NaCl) 3583, 3025, 2969, 1446, 1375 and 895; δH (200
MHz, CDCl3) 7.23–7.49 (10H, m), 2.83 (1H, dd, J 12 and 3.4),
1.65–1.92 (2H, m), 1.63 (1H, s, OH), 1.25–1.47 (2H, m), 0.45–
0.65 (6H, m); m/z (EI) 237 ([M Ϫ OH]ϩ, 84), 236 ([M Ϫ H2O]ϩ,
41), 225 (35), 223 (23), 207 (54), 165 (47), 135 (100), 91 (22); m/z
(positive CI, NH3) 272 ([M ϩ NH4]ϩ, 5.5), 255 ([M ϩ 1]ϩ, 5),
254 (Mϩ, 23), 237 ([M Ϫ OH]ϩ, 100) (Found: C, 84.75; H, 8.67.
C18H22O requires: C, 84.99; H, 8.72).
Similar treatment of 2-phenyl-2,7,7-trideuteriocyclo-
heptanone yielded [2H3]-7; mp 57 ЊC (Found: C, 84.79; H, 8.36.
Calc. for C19H19D3O: C, 84.7; H, 8.23%). Mass spectrometric
1,5-Diphenylpentan-1-one and 1,5-diphenylpentane
Low pressure hydrogenation of cinnamylideneacetophenone
over 10% Pd/C yielded the ketone with properties in accord
with literature data.31
2
2
analysis (positive CI) gave incorporation: H, 1.2 ± 0.1%, H2
2
6.6 ± 0.1% and H3 92.2 ± 0.1%).
Prolonged exposure to the hydrogenation conditions yielded
a hydrocarbon: bp 100–105 ЊC (0.2 mmHg), and identified as
1,5-diphenylpentane; νmax/cmϪ1 (NaCl) 3084, 2930, 2855, 1604,
1495, 1089, 906; δH (CDCl3) 7.15–7.38 (10H, m), 2.65 (4H, t, J
7.5), 1.7 (4H, quintet, J 7.5), 1.45 (2H, m); m/z (EI) 224 (Mϩ,
30), 133 (16), 117 ([Ph (CH2)3]ϩ, 6), 92 ([PhCH3]ϩ, 100), 77 (9);
m/z (positive CI, NH3) 242 ([M ϩ NH4]ϩ, 100), 240 (4), 224
(Mϩ, 2.8), 108 (11), 91 (14).
trans-1,2-Diphenylcyclooctanol, 8
A solution of 2-phenylcyclooctanone (0.8 g, 4 mmol) in 20 ml
of dry diethyl ether was added dropwise to a stirred phenyl-
lithium solution (25 ml of a 0.8  solution in diethyl ether). The
mixture was allowed to stir and reflux overnight before quench-
ing with saturated aqueous ammonium chloride. Extraction
with diethyl ether, drying (MgSO4) and evaporation yielded an
oil, containing about 40% of unreacted ketone. The oil was
heated under reflux for 2 h with Girard reagent ‘T’ (1.0 g in 9 ml
of ethanol and 1 g of acetic acid) and the alcohol was then iso-
lated by adding the mixture to water, neutralising with sodium
carbonate and extracting with diethyl ether. Evaporation of the
extracts and recrystallisation from light petroleum gave white
crystals, 0.5 g (45%), mp 73–74 ЊC (lit.,30 mp 73.5–74.5 ЊC)
(Found: C, 85.8; H, 8.7. Calc. for C20H24O: C, 85.6; H, 8.6%);
νmax/cmϪ1 (NaCl) 3563, 3058, 2921, 2852, 1492, 1447, 1325,
1035 and 758 and 701; δH (200 MHz, CDCl3) 1.5–2.1 (11H, m),
2.28 (1H, t, J 8.5, methylene), 2.58 (1H, m, methylene), 3.47
(1H, d, J 7.7, methine) and 6.9–7.37 (10H, m, ArH); δC(75
MHz, CDCl3) 22.4, 24.9, 26.9, 30.26, 30.69, 38.4, 52.2, 78.2,
125.2, 125.8, 126.1, 127.67, 127.75, 129.5, 145 and 147.6; m/z
(EI) 280 (Mϩ, 5), 262 ([M Ϫ H2O]ϩ, 17.6), 158 (89), 133 (87),
120 (100), 105 (86) and 91; (CI, NH3) 298 ([M ϩ NH4]ϩ, 7.6),
280 (Mϩ, 10), 263 ([M Ϫ OH]ϩ, 100).
4-Phenylbutyraldehyde, 5-phenylvaleraldehyde and 6-phenyl-
hexanal
These were prepared from commercially available phenyl-
alkanols by DMSO–oxalyl chloride oxidation.32
4-Phenylbutyraldehyde (95%), bp 70–75 ЊC (0.3 mmHg);
νmax/cmϪ1 (NaCl film) 3027, 2938, 1723, 1603, 1497, 1454, 749
and 700; δH (200 MHz, CDCl3) 1.98 (2H, quintet, J 8), 2.47 (2H,
dt, J 8 and 1.5), 2.65 (2H, t, J 8), 7.12–7.4 (5H, m) and 9.77 (1H,
t, J 1.5); m/z (EI) 148 (Mϩ, 18), 105 ([PhCH2CH2]ϩ, 14), 104
([PhCH᎐CH ]ϩ, 100), 91 ([PhCH ]ϩ, 73) and 78 (8); m/z (posi-
᎐
2
2
tive CI, NH3) 166 ([M ϩ NH4]ϩ, 100), 148 (Mϩ, 20), 104 (100)
and 91 (48).
5-Phenylvaleraldehyde (94%), colourless liquid, bp 75–80 ЊC
(0.4 mmHg); νmax/cmϪ1 (NaCl) 3027, 2936, 1724, 1497, 700 and
666; δH (200 MHz, CDCl3) 9.77 (1H, t, J 1.5), 7.1–7.4 (5H, m),
2.65 (2H, m), 2.4 (2H, m) and 1.6–1.7 (4H, m); m/z (EI) 162
(Mϩ, 6), 160 ([M Ϫ 2]ϩ, 4), 104 (41) and 91 (100); m/z (positive
CI, NH3) 180 ([M ϩ NH4]ϩ, 100), 162 (Mϩ, 4), 160 ([M Ϫ 2]ϩ,
4) and 91 (7).
6-Phenylhexanal (95%), colourless oil, bp 80–85 ЊC (0.4
mmHg); νmax/cmϪ1 (NaCl) 3062, 2934, 1724, 1604, 1497, 1454,
1030, 748 and 666; δH (200 MHz, CDCl3) 9.9 (1H, t, J 1.5), 7.12–
7.37 (5H, m), 2.65 (2H, t, J 7.5), 2.37 (2H, t, J 7.5), 1.57–1.70
(4H, m) and 1.34–1.50 (2H, m); m/z (EI) 176 (Mϩ, 16), 174
([M Ϫ 2]ϩ, 5), 130 (60), 105 (21), 92 (32) and 91 (100); m/z
(positive CI, NH3) 194 ([M ϩ NH4]ϩ, 100), 176 (Mϩ, 18), 130
(20) and 91 (21).
Reaction of 2-phenyl-2,8,8-trideuteriocyclooctanone (0.82 g,
4 mmol) similarly yielded 0.5 g (50%) of pure alcohol, mp
73–74 ЊC (Found: C, 85; H, 8.4. Calc. for C20H21D3O: C,
84.75; H, 8.48%). Mass spectrometric analysis (positive CI)
gave incorporation: 2H1 0.9 ± 0.1%, 2H2 10.6 ± 0.1%, 2H3
87.3 ± 0.1%.
erythro- and threo-3,4-Diphenylhexan-3-ol, erythro- and threo-9
A mixture of propiophenone (4.02 g, 30 mmol) and 1-chloro-1-
phenylpropane (5.56 g, 36 mmol) was added slowly to a
solution of lithium naphthalenide (from lithium, 0.59 g and
J. Chem. Soc., Perkin Trans. 2, 1997
1593

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1,6-Diphenylhex-2-en-1-one, 1,7-diphenylhept-2-en-1-one and
1,8-diphenyloct-2-en-1-one
their anions were prepared by the method of Arnett et al.,18
stored under argon on a gas line, and transferred gas tight by
syringe. The reaction vessel was a cylindrical glass flask fitted
with a thermostatically controlled water jacket, and linked dir-
ectly to a high vacuum manifold. About 15 mg of each alcohol
together with 10 mg of 1,5-diphenylpentane or dibenzyl ether
(internal standards) were weighed accurately and placed in the
reaction vessel. A small crystal of triphenylmethane was also
added. The apparatus was evacuated, and the vacuum then
released to argon. Dry DMSO or 1,3-diaminopropane (5 ml)
was injected. After ca. 30 min, a solution of metal dimsyl or
metal diaminopropanamide (0.2 ml of 0.2 ) was injected as
quickly as possible into the stirring alcohol solution using a gas
tight 5 ml syringe to initiate reaction. Portions of the reacting
mixture (0.2 ml) were syringed out at appropriate time intervals,
quenched in 1 ml of cold 0.2  HCl solution, and organic
material was extracted into 1 ml of distilled light petroleum 40–
60 for analysis by GLC. Ratios of the substrate peak areas to
internal standard peak area (Y) and reaction time (X) were
fitted to an equation of the form: Y = A1 exp [A2(ϪX)] where
A1 = initial value of Y, and A2 = rate constant using a non-
linear least square fitting process (PASSAGE f.00). The values
of A1 and A2 were allowed to vary in obtaining the best fit, and
values of A1 thus obtained agreed with measured values within
experimental uncertainty in all cases.
These were prepared by reaction of the aldehydes with benzoyl
methylene(triphenyl)phosphine33 in refluxing toluene. Addition
of light petroleum precipitated remaining Wittig reagent and
triphenylphosphine oxide which were filtered and discarded.
Remaining impurities of Wittig reagent and triphenylphos-
phine oxide were removed using a short column of alumina.
Evaporation of solvent and bulb-to-bulb distillation yielded the
ketones as colourless oils.
1,6-Diphenylhex-2-en-1-one (93%) had bp 100–105 ЊC (0.3
mmHg); νmax/cmϪ1 (NaCl) 3026, 2929, 1670, 1449, 1339, 1244
and 748; δH (200 MHz, CDCl3) 7.92 (2H, d, J 6.5), 7.4–7.6 (4H,
m), 7.1–7.35 (6H, m), 2.7 (2H, t, J 7.5), 2.37 (2H, q, J 7.5), 1.88
(2H, quin, J 7.5); m/z (EI) 251 ([M ϩ 1]ϩ, 5), 146 (38), 130 (48),
115 (42), 105 (96), 104 (57), 91 (100) and 77 (62); m/z (positive
CI, NH3) 268 ([M ϩ NH4]ϩ, 50), 251 ([M ϩ 1]ϩ, 100), 146 (6.5),
130 (8), 105 (8), 104 (6.5), 91 (5) and 78 (8).
1,7-Diphenylhept-2-en-1-one (87%) had bp 130 ЊC (0.5
mmHg); νmax/cmϪ1 (NaCl) 3026, 2932, 1671, 1496, 1449, 1283,
1223, 1128 and 748; δH (CDCl3) 7.95 (2H, m), 7.4–7.7 (3H, m),
7.05–7.38 (7H, m), 2.48–2.73 (4H, m) and 1.48–1.85 (4H, m);
m/z (EI) 264 (Mϩ, 4.5), 144 (19), 117 (14), 105 (100), 91 (85) and
77 (59); m/z (positive CI, NH3) 298 (22), 282 ([M ϩ NH4]ϩ,
28), 265 ([M ϩ 1]ϩ, 100), 180 (27), 166 (22), 149 (20), 105 (29)
and 91 (15).
1,8-Diphenyloct-2-en-1-one (80%) had bp 125–130 ЊC (0.4
mmHg); νmax/cmϪ1 (NaCl) 3026, 2932, 1671, 1449, 1283 and
696; δH (200 MHz, CDCl3) 7.95 (2H, m, ArH), 7.42–7.66 (3H,
m, ArH), 7.1–7.35 (7H, m), 2.52–2.75 (4H, m), 1.53–1.80 (4H,
m) and 1.35–1.52 (2H, m); m/z (EI) 278 (Mϩ, 2), 117 (13), 105
(75), 91 (100) and 77 (28); m/z (positive CI, NH3) 296
([M ϩ NH4]ϩ, 14), 295 (15), 279 ([M ϩ 1]ϩ, 100), 277 (20), 157
(16), 105 (80) and 91 (38).
Isotopic labelling studies
The apparatus and the conditions were those used for rate
measurements. About 50 mg of deuteriated alcohol was placed
in the apparatus and dissolved in DMSO or DAP as before. A
control sample was syringed out and quenched with 2 ml of
HCl (2% solution) before initiation of reaction by addition of
base. Further samples were then taken after two and ten
half-lives and quenched, and extracted and dried as before.
Ketonic product was isolated by bulb-to-bulb distillation, dis-
solved in 20 ml of dry dioxane, then refluxed with a solution of
potassium carbonate (0.5 g) in distilled water (10 ml). Diethyl
ether extraction as before yielded samples for analysis by GC–
MS to measure content deuterium and site of the residual
deuterium.
1,6-Diphenylhexan-1-one, 1,7-diphenylheptan-1-one, and 1,8-
diphenyloctan-1-one
These were prepared by low pressure hydrogenation of the 1,n-
diphenylalk-2-en-1-ones over 10% Pt/C in ethyl acetate solu-
tion. After uptake of one equivalent of hydrogen, the catalyst
was separated by filtration through Celite, the filtrate was con-
centrated and chromatographed on silica (elution with 20%
diethyl ether–light petroleum to give the ketones.
Kinetic isotope effect measurements
The apparatus was the same as for rate measurements described
above, and a ca. 1:1 mixture of deuteriated and non-deuteriated
1,2-diphenylcycloalkanols (50 mg) was placed in the reaction
vessel, together with the internal reference. Three to five
samples (1 ml each) were syringed out at time intervals from
the beginning of the reaction until the third half-life, quenched
in 3 ml of cold 0.2  HCl solution, organic materials extracted
with diethyl ether (5 ml), and washed with 3% aqueous NaCl (3
ml) and dried (MgSO4). The samples, together with a control
sample taken before addition of the base, were analysed by
capillary GLC using a 5 m × 0.22 mm OV1 column. Analysis of
deuterium content of the remaining substrates was performed
by GC–MS using positive CI mass spectral data. More than ten
scans were normally taken for each sample at relatively high
and consistent ion current for the m/z region of interest. Kinetic
isotope effects were calculated using relationships described in
the main text. For the cyclooctanol, [2H3]-8, reacting in dimsyl-
sodium at 20 ЊC values of kH /kD obtained were 1.42 (α =
1,6-Diphenylhexan-1-one: bp 125–130 ЊC (0.3 mmHg); νmax
/
cmϪ1 (NaCl) 3085, 2932, 1686, 1598, 1496, 1216 and 749;
δH (200 MHz, CDCl3) 7.98 (2H, d, J 7.5), 7.42–7.62 (3H, m),
7.13–7.35 (5H, m), 2.97 (2H, t, J 7), 2.65 (2H, t, J 8), 1.6–1.9
(4H, m) and 1.36–1.54 (2H, m); m/z (EI) 253 ([M ϩ 1]ϩ, 17),
252 (Mϩ, 12), 133 (44), 130 (94), 120 (91), 105 (100) and 91 (37);
m/z (negative CI, NH3) 252 (M, 18), 251 ([M Ϫ 1]Ϫ, 100), 121
(3), 119, (2), 91 (1.2) and 87 (3).
1,7-Diphenylheptan-1-one: bp 140 ЊC (0.3 mmHg); νmax/cmϪ1
(NaCl) 3026, 2931, 1686, 1598, 1496, 1211 and 749; δH (200
MHz, CDCl3) 7.96 (2H, d, J 7.5, ArH), 7.52 (3H, m, ArH),
7.13–7.38 (5H, m, ArH), 2.97 (2H, t, J 8), 2.64 (2H, t, J 7.5),
1.58–1.88 (4H, m) and 1.3–1.55 (4H, m); m/z (EI) 267
([M ϩ 1]ϩ, 14), 266 (Mϩ, 15), 144 (66), 133 (42), 120 (91), 105
(100), 91 (32); m/z (positive CI, NH3) 267 ([M ϩ 1]ϩ, 100), 120
(24) and 105 (38); m/z (negative CI, BuONO) 265 ([M Ϫ 1]Ϫ,
100), 263 (3.5) and 177 (1.5).
3
3
1,8-Diphenyloctan-1-one: bp 150 ЊC (0.3 mmHg), mp 46–
47 ЊC; νmax/cmϪ1 (NaCl) 3026, 2921, 1449, 1367, 1073 and 909;
δH (200 MHz, CDCl3) 7.97 (2H, d, J 7.5), 7.42–7.62 (3H, m),
7.13–7.35 (5H, m), 2.97 (2H, t, J 7.5), 2.6 (2H, t, J 7.5), 1.55–
1.85 (4H, m), 1.28–1.48 (6H, m); m/z (EI) 281 ([M ϩ 1]ϩ, 10),
280 (Mϩ, 4), 158 (80), 133 (48), 120 (97), 105 (100), 91 (43); m/z
(negative CI, BuONO) 280 (Mϩ, 20), 279 ([M Ϫ 1]Ϫ, 100).
0.380), 1.49 (α = 0.260), 1.50 (α = 0.125), 1.46 (α = 0.037) and
1.30 (α = 0.022); for the cycloheptanol, [2H3]-7, reacting in
dimsylsodium at 40 ЊC, values were 1.34 (α = 0.54), 1.44
(α = 0.158), 1.32 (α = 0.003); for the cyclopentanol, [2H3]-5,
reacting in dimsylpotassium at 50 ЊC, values were 2.41 (α =
0.478), 2.50 (α = 0.240) and 2.50 (α = 0.009).
X-Ray structure determinations
Rate measurements
DMSO and 1,3-diaminopropane were purified, and solutions of
Details of crystal data and of the measurements and solution
are in Tables 5 and 6. Measurements were made on a Rigaku
1594
J. Chem. Soc., Perkin Trans. 2, 1997

View Article Online
Table 5 Crystal data for trans-1,2-diphenylcycloalkanols, and erythro-3,4-diphenylhexan-3-ol
Parameter
Cyclopentanol, 5
Cyclohexanol, 6
Cycloheptanol, 7
Cyclooctanol, 8
Hexanol, 9
Empirical formula
C17H18O
C18H20O
C19H22O
C20H24O
C9H11O0.5
Formula mass
238.33
252.36
266.38
280.41
127.19
Crystal colour and habit
Crystal dimensions/mm
Crystal system
Colourless, acicular
0.5 × 0.12 × 0.50
monoclinic
Colourless tabular
0.07 × 0.25 × 0.25
monoclinic
Colourless prisms
0.4 × 0.45 × 0.50
triclinic
Colourless prismatic
0.30 × 0.60 × 0.60
monoclinic
Colourless prismatic
0.23 × 0.25 × 0.30
monoclinic
Number of reflections
25 (29.3 Ϫ 36.6Њ)
25 (1.26 ϩ 0.3 tan θ)
25 (29.3 Ϫ 34.9Њ)
25 (29.3 Ϫ 34.9Њ)
24 (76.9 Ϫ 79.8Њ)
for unit cell
determination (2θ
range)
ω-Scan peak width
0.03
0.29
0.25
0.22
0.22
half height
Lattice parameters
a/Å
b/Å
c/Å
α/Њ
β/Њ
9.184(2)
20.528(6)
7.856(3)
13.563(2)
5.932(2)
18.380(3)
11.779(3)
11.984(6)
11.393(1)
95.60(4)
106.71(2)
93.89(3)
1525(1)
P1 (No. 2)
4
1.160
576
8.124(2)
21.632(4)
9.906(3)
8.0343(8)
8.9286(4)
11.0351(6)
114.65(2)
107.28(2)
111.32(2)
106.983(6)
γ/Њ
V/Å3
Space group
Z
1346(2)
Pc (No. 7)
4
1.176
512
15411.9(6)
P21 /n (No. 14)
4
1.187
544
1622(1)
P21 /c (No. 14)
4
1.148
608
761.67(9)
P21 /c (No. 14)
4
1.109
276
¯
Dc/g cmϪ3
F000
µ/cmϪ1
5.16 (Cu-Kα)
5.16 (Cu-Kα)
5.00 (Cu-Kα)
4.91 (Cu-Kα)
4.78 (Cu-Kα)
Table 6 Intensity measurements, solution and refinement of crystal structures of trans-1,2-diphenylcycloalkanols, and erythro-3,4-diphenylhexan-
3-ol
Parameter
Cyclopentanol, 5
Cyclohexanol, 6
Cycloheptanol, 7
(1.31 ϩ 0.30 tan θ)
Cyclooctanol, 8
Hexanol, 9
Scan width/Њ
Scan rate/Њ minϪ1
Number of reflections
Total
(1.31 ϩ 0.30 tan θ)
16.0 (in ω), 2 rescans
(1.26 ϩ 0.30 tan θ)
8 (in ω), 3 rescans
(1.57 ϩ 0.30 tan θ)
(1.47 ϩ 0.30 tan θ)
32.0 (in ω), 2 rescans
32.0 (in ω), 2 rescans 32.0 (in ω), 2 rescans
2242
2445
4799
2691
1305
Unique
Ranges of
2233 (Rint = 0.032)
2346 (Rint = 0.108)
4541 (Rint = 0.077)
2491 (Rint = 0.081)
h
k
l
Ϫ10 to 9
Ϫ23 to 0
0 to 8
0 to 21
0 to 34
0 to 10
Ϫ5 to Ϫ13
Ϫ13 to 13
Ϫ12 to 12
0 to 9
0 to 24
Ϫ11 to 10
0 to 9
0 to 10
Ϫ12 to 11
Corrections
Trans. factors
Decay
0.69Ϫ1.13
0.50%
0.03
0.78Ϫ1.00
8.50%
0.03
0.81Ϫ1.07
3.6%
0.03
0.93Ϫ1.13
3.38%
0.02
0.69Ϫ1.33
1.67%
0.03
p-Factor
No. observations
[I > 3.00σ(I )]
No. variables
Reflection/parameter
Residuals R, Rw
1556
1564
3346
2859
1004
323
4.82
0.052, 0.060
182
8.59
0.055, 0.070
2.58
361
19.27
0.070, 0.089
3.18
334
8.56
0.064, 0.078
3.34
91
11.03
0.076, 0.119
4.67
Goodness of fit indicator 1.91
Max shift in final cycle
Max/min peaks in final
difference map/e ÅϪ3
<0.05
0.22 and 0.16
<0.05
0.20 and Ϫ0.15
<0.04
0.73 and Ϫ0.22
<0.01
0.49 and Ϫ0.19
<0.01
0.28 and Ϫ0.16
AFC5R X-ray diffractometer with graphite-monochromated
Cu-Kα (λ 1.541 78 Å) radiation. Attenuators were Zr foil
(factors 3.6, 12.2, 44.0). The data were collected at a tem-
perature of 20 ± 1 ЊC using the ω/2θ scanning technique to a
maximum 2θ value of 120.1Њ. ω Scans of several intense reflec-
tions, made prior to data collection, had an average width at
half-height of 0.22Њ with a take-off angle of 6Њ. The weak reflec-
tions [l < 10σ(l)] were rescanned and the counts were accumu-
lated to assure good counting statistics. Stationary background
counts were recorded on each side of the reflection. The ratio of
peak counting time to background counting time was 2:1. The
diameter of the incident beam collimator was 0.5 mm and the
crystal to detector distance was 400 mm utilising a continuously
evacuated beam tunnel to reduce absorption by air. The inten-
sities of three representative reflections were measured after
every 150 reflections, and a linear correction factor was applied
to the data to compensate small observed decays. Empirical
absorption corrections, using the program DIFABS,34 were
applied resulting in the tabulated transmission factors. Data
were corrected for Lorentz-polarisation effects and absorption,
and the structure was solved by direct methods.35 Hydrogen
atoms were placed in calculated positions (C᎐H = 0.95 Å) or
located in difference Fourier transforms. The refinement was by
full-matrix least-squares minimisation of w(Fo Ϫ Fc)2, with
2
w = 4Fo /σ2(Fo)2. Non-hydrogen atoms were refined aniso-
tropically; hydrogen atoms were assigned isotropic thermal
parameters 20% greater than the equivalent B value of the atom
to which they were bonded. Atomic scattering factors were cal-
culated according to Cromer and Waber.36 Anomalous disper-
sion effects were included in Fc.37 All calculations were carried
out on a VAXstation 3520 with the TEXSAN package.38
Molecular diagrams were obtained with ORTEP 39 or with
PLUTO.40 In the final cycle of full-matrix least-squares refine-
ment, the weighting scheme was based on counting statistics
and included a factor (p) to downweight the intense reflections.
Plots of Σw(|Fo| Ϫ |Fc|)2 versus |Fo|, reflection order in data
J. Chem. Soc., Perkin Trans. 2, 1997
1595

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13 H. Zook, J. March and D. Smith, J. Am. Chem. Soc., 1959, 81, 1617.
14 E. M. Arnett, L. E. Small, R. T. McIver and J. S. Miller, J. Org.
Chem., 1978, 43, 815.
15 J. Lomas and J. Dubois, J. Org. Chem., 1984, 49, 2067.
16 For collected pKa data see F. G. Bordwell, Acc. Chem. Res., 1988, 21,
456; R. W. Taft and F. G. Bordwell, Acc. Chem. Res., 1988, 21,
463.
17 J. H. Exner and E. C. Steiner, J. Am. Chem. Soc., 1974, 96, 1782.
18 E. M. Arnett, K. G. Venkatasubramian, R. T. McIver Jr.,
F. G. Bordwell and R. D. Press, J. Org. Chem., 1983, 48, 1569.
19 M. I. Page, J. Mol. Catalysis, 1988, 47, 241; M. I. Page and
W. P. Jencks, Procl. Natl. Acad. Sci., USA, 1971, 68, 1678;
M. I. Page, Angew. Chem., Int. Ed., Engl., 1976, 16, 449.
20 I. A. Shapiro and N. G. Zharova, Zh. Org. Khim., 1989, 25, 1813 (see
Chem. Abstr., 1989, 112, 138 516; 1989, 113, 114576z.
21 J. E. Homan, R. J. Muller and A. Schriesheim, J. Am. Chem. Soc,
1963, 85, 3000 and 3002; D. W. Boerth and A. Streitwieser Jr., J. Am.
Chem. Soc., 1981, 103, 6443.
collection, sin θ/λ, and various classes of indices showed no
unusual trends. Crystal data and further details of the
measurements and solution are tabulated.
Fractional coordinates, bond lengths and angles, torsion
angles for non-hydrogen atoms and other relevant structural
and experimental details have been deposited at the Cambridge
Crystallographic Data Centre.†
Empirical forcefield calculations
The molecular modelling package was MACROMODEL 4.5,11
running on a Silicon Graphics 4D 240 GTX work station. The
MM3* forcefield of Allinger et al.10 was used for calculations
with no modification of parameters.
Acknowledgements
22 L. Melander and W. H. Saunders Jr., Reaction Rates of Isotopic
Molecules, Wiley, New York, 1980, pp. 95–102.
23 A. Streitweiser Jr., R. H. Jagow, R. C. Fahey and S. Suzuki, J. Am.
Chem. Soc., 1958, 80, 6764.
We wish to thank the Islamic Republic of Iran for support in
the form of a studentship to Mr S. M. Moosavi.
24 J. J. Gajewski and K. R. Gee, J. Am. Chem. Soc., 1991, 113, 967.
25 N. J. Harris and J. J. Gajewski, J. Am. Chem. Soc., 1994, 116, 6121.
26 F. H. Westheimer, Chem. Rev., 1961, 61, 265.
27 For collected data on kie dependences on ∆pKa see Proton Transfer
Reactions, ed. E. Caldin and V. Gold, Chapman and Hall, London,
1975, pp. 222–227.
† For details of the CCDC deposition scheme see ‘Instructions for
Authors’, J. Chem. Soc., Perkin Trans. 2, 1997, Issue 1. Any request to
the CCDC for this material should quote the full literature citation and
the reference number 188/72.
28 K. Biemann, Mass Spectrometry: Organic Chemical Applications,
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Paper 6/07548G
Received 5th November 1996
Accepted 14th March 1997
1596
J. Chem. Soc., Perkin Trans. 2, 1997