Impact of the α-Ferrocenyl Group on the Solvolytic Reactivity – Electrofugality – of Ferrocenylphenylmethyl Cations

Article abstract of DOI:10.1002/ejoc.201801133

The electron-donating effect of the ferrocenyl group in α-position to the reaction center on S_N1 solvolytic reactivity has been quantified by determining the electrofugalities (E_f) of a series of ferrocenyl-X-phenylmethyl cations according to the LFER equation: log k = s_f(E_f + N_f). Due to highly stabilized transition state, the E_f values are about eight units higher than those of the corresponding benzhydryl cations. Impact of the phenyl group in ferrocenylphenylmethyl derivatives on stabilization of the positive charge is somewhat leveled by the ferrocenyl group, so the rate effect of the substituents on the phenyl ring is suppressed, causing narrow range of E_f parameters and small absolute values of the ρ⁺ constant. Calculations at B2PLYP-D3/may-cc-pVTZ level of theory showed that the positive charge in ferrocenylphenylmethyl cation is largely shifted from the phenyl to ferrocenyl moiety, and that the substituents on the phenyl ring have small impact on its stability.

Full text of DOI:10.1002/ejoc.201801133

A Journal of
Accepted Article
Title: Impact of the α-Ferrocenyl Group on Solvolytic Reactivity -
Electrofugality of Ferrocenylphenylmethyl Cations
Authors: Marijan Marijan, Sandra Jurić, Zlatko Mihalić, and Olga Kronja
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201801133
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10.1002/ejoc.201801133
European Journal of Organic Chemistry
FULL PAPER
Impact of the α-Ferrocenyl Group on Solvolytic Reactivity
− Electrofugality of Ferrocenylphenylmethyl Cations
Marijan Marijan,[a] Sandra Jurić,[a] Zlatko Mihalić,[b] and Olga Kronja*[a]
Abstract: The electron-donating effect of the ferrocenyl group in α-
position to the reaction center on SN1 solvolytic reactivity has been
quantified by determining the electrofugalities (Ef) series of
ferrocenyl-X-phenylmethyl cations according to LFER equation: log k
= sf(Ef + Nf). Due to highly stabilized transition state, the Ef values
are about eight units higher than those of the corresponding
the Hammett-Brown parameter (ρ+ = –1.4 at 0°C in 80% aq.
acetone) in comparison to ρ+ values obtained for similar systems
(e.g. ρ+ = –5.63 for X-substituted benzhydryl derivatives and ρ+ =
–3.98 for X-substituted trityl derivatives at 0°C in 80% aq.
acetone).[4]
We have now revisited the solvolytic reactivity of the
substrates with the ferrocenyl group in α-position to the reaction
center in order to quantify its contribution to SN1 reactivity. We
have examined the solvolytic behavior of the series of
benzhydryl
cations.
Impact
of
the
phenyl
group
in
ferrocenylphenylmethyl derivatives on stabilization of the positive
charge is to somewhat levelled by the ferrocenyl group, so the rate
effect of the substituents on the phenyl ring is suppressed, causing
narrow range of Ef parameters and small absolute values of the ρ+
constant. Calculations at B2PLYP-D3/may-cc-pVTZ level of theory
showed that the positive charge in ferrocenylphenylmethyl cation is
largely shifted from the phenyl to ferrocenyl moiety, and that the
substituents on the phenyl ring have small impact on its stability.
ferrocenylphenylmethyl
(ferrocenylbenzyl)
acetates
and
benzoates 1-LG (Scheme 1) by determining the abilities of the
ferrocenylphenylmethyl cations 1 to leave the substrate, i.e., by
defining their electrofugality.
LG
k
+
LG
products
Fe
Fe
solvent
Introduction
X
X
1
1-LG
LG = CH3COO, C6H5COO
a) X = H, b) 4-Br, c) 4-Cl,d) 3-F, e) 3-Br, f) 3-Cl, g) 3,5-Cl2
Kinetic studies established that the ferrocenyl group (Fc) in
α-position to the reaction center considerably enhances the SN1
solvolytic reactivity of the substrate.[1] For example, ferrocenyl-
methyl acetate solvolyzes about seven times faster than
triphenylmethyl acetate (trityl acetate) in 80% aq. acetone at
30 °C, demonstrating that the effect of one ferrocenyl group on
reactivity is more pronounced than that of the three phenyl
groups.[1b]
Enhanced reactivity of the ferrocenyl derivatives comes from
the stability of the ferrocenylmethyl cations, which has mainly be
attributed to very efficient delocalization of the positive charge.[2]
Their stability is shown with pKR+ values (e.g. pKR+ = 0.49 for
ferrocenylphenylmethyl cation at 0 °C vs. pKR+ = −6.63 for trityl
cation 0 °C in aqueous acidic solution),[ 3 ] as well as with
existence of the stable ferrocenylmethylium salts (e. g. as
tetrafluoroborates) at ambient temperature.
Scheme 1. Heterolytic step in solvolysis of ferrocenylphenylmethyl derivatives.
To quantify the contribution of the α-Fc group, we have
chosen the electrofugality scale developed on the basis of
solvolytic reactivity of X,Y-substituted benzhydryl derivatives.[5,6]
Similarly as reported for the combination reactions between the
electrophile and the nucleophile, whose rates can be calculated
according to the following equation: log k = s (N + E) (N =
nucleophilicity and E = electrophilicity),[ 7 ] the first-order rate
constant k of the heterolytic step in SN1 solvolysis can be
calculated according to the three parameters linear free energy
relationship (LFER) [Equation (1)]:
log k (25 °C) = sf(Nf + Ef)
(1)
Kinetic data available for ferrocenylphenylmethyl acetates
revealed that unlike the presence of the α-ferrocenyl group,
which causes pronounced rate enhancement in solvolysis, the
effect of the substituent X in X-phenylFcCH− group is only
moderate. This is indicated with the reduced absolute value of
in which Ef is a solvent independent variable representing the
electrofugality of the generated carbocation, i.e., its quantified
ability to leave the substrate, while Nf (nucleofugality) and sf
(slope parameter, the reaction constant) are the nucleofuge
specific parameters, referring to the ability of the leaving group
to leave the substrate in a given solvent. This method makes
feasible estimating the solvolytic reactivity in a given solvent of
any substrate constituted from an electrofuge of known Ef
parameter and a nucleofuge of known sf and Nf parameters.
We set out here to determine the electrofugality values for
the series of ferrocenylphenylmethyl cations (a) to facilitate
comparison of their abilities of the to leave the substrate with
the abilities of numerous other electrofuges determined earlier,
(b) to enable estimating the absolute first-order heterolysis
[a]
[b]
M. Marijan, Prof. Dr. S. Jurić, Prof. Dr. O. Kronja,
University of Zagreb, Faculty of Pharmacy and Biochemistry
Ante Kovačića 1, 10000 Zagreb, Croatia
okronja@pharma.hr
Prof. Dr. Z. Mihalić,
University of Zagreb, Faculty of Sciences
Department of Chemistry
Horvatovac 105a, 10000 Zagreb, Croatia
Supporting information for this article is given via a link at the end of
the document.
1
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10.1002/ejoc.201801133
European Journal of Organic Chemistry
FULL PAPER
rates
for
substrates
that
are
combination
of
Therefore, before examining the electrofugalities of the series of
ferrocenylphenylmethyilium cations, we have extended the data
for nucleofugalities of acetate in some solvents.
ferrocenylphenylmethyl moiety and any nucleofuge in a given
solvent at 25 °C simply by applying the electrofugalities
determined here and the published nucleofuge-specific
parameters (sf and Nf) into Equation (1), and (c) to get a closer
insight into the electronic effects in the ferrocenyl substituent
that influence on the substrate reactivity, based on experimental
results and quantum chemical calculations.
Benzhydryl acetates with reactive benzhydryl moieties
(Scheme 2), which were chosen from the set of reference
electrofuges,[5] were prepared from the corresponding
benzhydrols according to procedures given in the Experimental
Section. The first-order solvolysis rate constants measured are
presented in Table S1 in the Supporting Information. To obtain
the nucleofugality parameters (Nf and sf), the logarithms of the
first-order rate constants in the given solvents were plotted
against the reference Ef values, as presented in Figure 1.
According to Equation (1), Nf is the negative intercept on the
abscissa of a given plot, whereas sf is its slope. The values of
the nucleofuge specific parameters (Nf and sf) for acetate in
solvents used here are presented in Table S3 (Supporting
Information).
Using the correlation presented with Equation (1), the
nucleofuge specific parameters (sf and Nf) of large number of the
anionic and neutral leaving groups in the series of solvents have
previously been determined from the solvolysis rate constants of
benzhydryl derivatives.[8,9] Taking those earlier determined sf ,
and Nf parameters, the electrofugality parameter (Ef) of a given
electrofuge (carbocation) can be derived from log k/sf versus Nf
plots. Such approach for determining the electrofugalities of the
cations that are not benzhydrylium ions is applicable if,
according to Equation (1), the log k/sf versus Nf correlations
produce linear plots with the slopes of unity. For example,
electrofugalities of differently substituted trityl cations have been
determined using the above equation.[10] It turned out that trityl
chlorides and bromides are good substrates for obtaining the
electrofugalities of the corresponding trityl cations correctly,
since they produce k/sf vs. Nf lines whose slopes are unity.
However, trityl acetates produce steeper log k/sf versus Nf plots
(slope ≈ 1.2), indicating that carboxylates are better nucleofuges
if the substrate is trityl carboxylate than if it is benzhydryl
carboxylate.
log k
-2.0
X=Fur
Y=Fur
60M40W
X=Fur
Y=OMe
-2.5
-3.0
-3.5
-4.0
-4.5
-5.0
-5.5
80M20W
X=OMe
Y=OMe
90M10W
80E20W
100M
90E10W
X=OMe
Y=OPh
X=OMe
Y=Me
Results and Discussion
Kinetic data available from literature show that
ferrocenylphenylmethyl cations (1) represent very efficient
electrofuges.[11] A comparison of the electrofugality parameters
Ef with the electrophilicity parameters E shows that in most
cases linear correlation exists, i.e., Ef ≈ –E. Even though the
correlation somewhat breaks down for highly stabilized ions (E <
2), the electrophilicity value for ferrocenylphenylmethyl cation (E
-1.5
-1.0
-0.5
0.0
0.5
1.0
E
f
Figure 1. Plots of log k (25 °C) versus Ef for solvolyses of substituted
benzhydryl acetates in pure and aqueous alcoholic solvents. Binary solvents
are given as v/v. E = ethanol, M = methanol, and W = water. The values of k
–2.64)[7a] can be taken as
a rough prediction of its
for dianysylmethyl acetate (X
parameters are taken from ref 5.
= Y = 4-OMe) is taken from ref. 12. Ef
=
electrofugality (Ef ≈ 2 to 3). In order to adjust the rate constants
to enable kinetic measurements by conventional methods
available for us, such good electrofuges should be combined
with weak nucleofuges (poor leaving groups). So far, the poorest
negatively charged nucleofuges on the nucleofugality scale
developed according to Equation (1) are acetate and benzoate
leaving groups. However, Nf and sf values for those nucleofuges
have been determined in a limited number of solvents.[12]
At this point, the extended set of nucleofugality parameters
for acetate and those existing for benzoate in various solvents
were available for determining the electrofugality of variety of
ferrocenylphenylmethyl
cations.
The
series
of
ferrocenylphenylmethyl acetates and benzoates (1-LG) (Scheme
1), prepared according to the procedure presented in the
Experimental Section, were subjected to kinetic measurements.
Solvolysis rates were measured titrimetrically (details are given
in Kinetic Methods in the Experimental Section) in a series of
pure and aqueous solvents at 25 °C or at least three different
temperatures and the rate constants were extrapolated to 25 °C
by using Eyring plot. The solvolytic first-order rate constants at
25 °C (experimental or extrapolated) of substituted
ferrocenylphenylmethyl acetates and benzoates (1-LG) are
OCOCH3
OCOCH3
OCOCH3
O
O
O
X
Y
CH3O
a) X = OCH3, Y = CH3, Ef = −1.32
b) X = OCH3, Y = OC6H5, Ef = −0.86
Ef = 1.07
Ef = 0.61
Scheme 2. Benzhydryl acetates used for determining the nucleofuge specific
parameters (Nf and sf) for of acetate in various solvents and the Ef values of
the corresponding electrofuges.
2
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10.1002/ejoc.201801133
European Journal of Organic Chemistry
FULL PAPER
presented in Table 1, while those obtained at lower
Table 1. Solvolysis rate constants of some substituted ferrocenylphenylmethyl
temperatures
along with the
corresponding
activation
acetates and benzoates in various solvents at 25 °C.
parameters are presented in Table S2 in the Supporting
Information.
Electrofuge[a]
LG[b]
Solvent[c]
k/s−1[d]]
C6H5FcCH+ (1a)
AcO−
100M
1.04 × 10−2[e]
To extract the electrofugalities of ferrocenylphenylmethyl
cations, log k/sf versus Nf were plotted for the series of
ferrocenylphenylmethyl acetates and benzoates (1-LG). The
weighted average of the slopes of seven correlation lines in
Figure 2 is 1.009 ± 0.005, verifying the LFER approach
presented above. The electrofugalities obtained from the
correlations are shown in Table 2, in which, for sake of
comparison, the electrofugality of the ferrocenylmethyl cation,
calculated from the published rate constants (last entry in Table
2),[13] as well as those of the corresponding benzhydryl cations
have been added.[5]
90E10W
80AN20W
80A20W
80AN20W
100M
8.89 × 10−3[e]
(3.78 ± 0.01) × 10−3
(1.38 ± 0.04) × 10−3
8.37 × 10−3[e]
6.21 × 10−3[e]
5.47 × 10−3[e]
BzO−
AcO−
4-BrC6H4FcCH+ (1b)
4-ClC6H4FcCH+ (1c)
3-FC6H4FcCH+ (1d)
3-BrC6H4FcCH+ (1e)
3-ClC6H4FcCH+ (1f)
90E10W
80AN20W
80A20W
80AN20W
80A20W
100M
(2.14 ± 0.03) × 10−3
(8.24 ± 0.06) × 10−4
(4.74 ± 0.1) × 10−3
(1.95 ± 0.04) × 10−3
5.71 × 10−3[e]
BzO−
AcO−
log k /sf
LG
-1.8
90E10W
80AN20W
80A20W
80AN20W
80A20W
100M
5.08 × 10−3[e]
H
(1.96 ± 0.03) × 10−3
(7.10 ± 0.01) × 10−4
(4.21± 0.1) × 10−3
(1.52 ± 0.02) × 10−3
3.12 × 10−3[e]
(2.60 ± 0.03) × 10−3
(1.03 ± 0.03) × 10−3
(3.67 ± 0.01) × 10−4
(2.21 ± 0.07) × 10−3
(8.17 ± 0.01) × 10−4
2.34 × 10−3[e]
(2.21 ± 0.06) × 10−3
(7.66 ± 0.01) × 10−4
(2.76 ± 0.01) × 10−4
(1.68 ± 0.03) × 10−3
(6.19 ± 0.01) × 10−4
2.36 × 10−3[e]
Fe
-2.0
-2.2
-2.4
-2.6
-2.8
-3.0
-3.2
-3.4
-3.6
4-Br
4-Cl
X
BzO−
AcO−
3-F
3-Cl
3-Br
AcO
90E10W
80AN20W
80A20W
80AN20W
80A20W
100M
100M
3,5-diCl
BzO
80AN20W
AcO
90E10W
BzO
BzO−
AcO−
AcO 80A20W
80AN20W
AcO
80A20W
-4.7
-4.6
-4.5
-4.4
-4.3
-4.2
90E10W
80AN20W
80A20W
80AN20W
80A20W
100M
N
f
Figure 2. Plots log k/sf against Nf for the solvolysis of substituted
ferrocenylphenylmethyl acetates and benzoates (1) in various solvents. AcO =
CH3COO, BzO = C6H5COO. Binary solvents are given as v/v. A = acetone, AN
= acetonitrile, E = ethanol, M = methanol, and W = water.
BzO−
AcO−
90E10W
80AN20W
80A20W
80AN20W
80A20W
90E10W
80AN20W
80A20W
80AN20W
80A20W
(2.20 ± 0.05) × 10−3
(7.85 ± 0.01) × 10−4
(2.83 ± 0.01) × 10−4
(1.71 ± 0.04) × 10−3
(6.33 ± 0.01) × 10−4
(8.24 ± 0.01) × 10−4
(2.66 ± 0.01) × 10−4
(8.81 ± 0.02) × 10−5
(5.70 ± 0.03) × 10−4
(1.97 ± 0.01) × 10−4
Effect of the Substituents on Reactivity
Having in mind that difference in electrofugality of one unit
represents the difference in reactivity of the substrate of about
one order of magnitude (Equation 1; all known values for sf are
in the narrow range between 0.80 and 1.36),[14] Ef parameters
presented in Table 2 indicate that replacement of the phenyl
group with ferrocenyl group drastically, for about eight orders of
magnitude, increases the reactivity of the substrate. On Figure 3
the electrofugalities of differently substituted benzhydrylium,
tritylium and ferrocenylphenylmethylium ions are compared. The
reactivity of trityl derivative is enhanced for about six order of
magnitude in comparison to the corresponding benzhydryl
derivative, due to the additional phenyl group stabilization of the
positive charge generated on the reaction center in the TS, and
also due to the steric repulsion in the ground state, i.e., back
strain effect.[10] Since in the ferrocenylphenylmethyl derivatives
1-LG the positive charge arises on the secondary carbon atom,
the ground state back strain is similar to that of the benzhydryl
BzO−
3,5-diClC6H3FcCH+ (1g) AcO−
BzO−
[a] Fc = ferrocene. [b] AcO = CH3COO, BzO = C6H5COO. [c] Binary solvents
are given as v/v at 25 °C; A = acetone, AN = acetonitrile, E = ethanol, M =
methanol, W = water. [d] Average rate constants from at least three runs
performed at 25 °C. Errors are standard deviations. [e] Extrapolated from data
at different temperatures (Table S2 in the Supporting Information) by using the
Eyring equation.
3
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10.1002/ejoc.201801133
European Journal of Organic Chemistry
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According to Ef values of ferrocenylphenylmethyl cations
(Table 2), it can easily be predicted that any substrate whose
electrofuge moiety is the ferrocenylphenylmethyl group is not
stable enough at ambient temperature to be handled safely in
aqueous solvent mixtures, regardless to the nucleofuge
structure. For example, the half-life of the substrate that is the
combination of the least reactive ferrocenylphenylmethyl cation,
1g (3,5-dichlorophenylferrocenylmethyl cation, Ef = 1.30) and the
poorest anionic leaving group (acetate in 80% aq. acetone; Nf =
−4.52, sf = 1.11)[5] is only about 40 minute at 25 °C. For
comparison, half-life of the unsubstituted trityl acetate in the
same solvent mixture and at the same temperature is about 4
days, while the half-life of the unsubstituted benzhydryl acetate
in 80% aq. acetone at 25 °C is about 800 years, showing that
benzhydryl acetate constitutes a very stable compound in
aqueous solvent mixtures.
Table 2. Electrofugality parameters of substituted ferrocenylphenylmethyl
cations and the corresponding benzhydryl cations
Ef
Substituent X
X-Benzhydryl cation[b]
Ferrocenyl-X-phenylmethyl
cation[a]
H
2.40
2.15
2.13
1.77
1.70
1.67
1.30
0.17
−6.03
−6.62
−6.44
−7.53
4-Br
4-Cl
3-F
3-Br
3-Cl
3,5-diCl
−7.69
Unlike large rate effects caused by replacement of one
hydrogen atom in the benzyl group with the ferrocenyl,
introduction of the phenyl group into the ferrocenylmethyl
derivatives causes only moderate increase of the solvolytic
ferrocenylmethyl
cation[c]
reaction rate. Thus, ferrocenylphenylmethyl derivatives (Ef
=
[a] this work. [b] Ef parameters for benzhydryl cations are taken from ref 5. [c]
Ef parameter for ferrocenylmethyl cation is calculated from rate constant of
ferrocenylmethyl acetate in 80% aqueous acetone (ref. 13) and from Nf and sf
values of acetate in 80% aqueous acetone (ref. 5) using Eq. (1) [log k = sf (Ef
+ Nf)].
2.40) solvolyze about two orders of magnitude faster than
ferrocenylmethyl derivatives (Ef = 0.17).
R
R
R
substrates, large rate enhancement in comparison to benzhydry
derivatives can be attributed only to electronic effects in the TS
in solvolysis of substrates 1-LG.
Ef = − 4.2
Ef = − 4.01
Ef = −11.0
Ef = − 5.14
Ef = −12.5
R = C6H5
R = H
Ef = − 11.1
Considering the relationship between electrophilicity and
electrofugality (Ef ≈ –E), it can be projected that introduction of
the second ferrocenyl group would further drastically increase
the reactivity for six orders of magnitude (E = −8.5 for
diferrocenylmethyl cation).[11]
R
R
R
Fe
CH3
CH3O
R = C6H5
R = H
Ef = −4.69
Ef = −9.52
Ef = −2.09
Ef = −6.33
Ef = +2.40
Ef = +0.17
Scheme 3. The effect of the phenyl group on electrofugality of some cations.
+
Fe
+
+
X
X
X
To evaluate this observation, it is useful to compare the
effects of the α-phenyl group on electrofugality of
ferrocenylmethyl cation with those of some other electrofuges,
as presented in Scheme 3.[6c] Replacement of the hydrogen with
a phenyl group in substrates that generate electrofuges that lack
additional stabilization by resonance (e.g. adamantyl, cyclooctyl
and isopropyl cation), increases the rate of carbocation
formation in the heterolytic step of SN1 reaction for about seven
orders of magnitude. However, if the group that stabilizes the
positive charge already exists in the electrofuge, the effect of the
additional phenyl group is diminished and depends on the
electron-donating ability of the existing group, i.e., the effect of
the electron-donating substituents covers the effect of the
additional phenyl group to some extent. Thus, introduction of the
phenyl ring into the substrate with the p-tolylmethyl moiety
increases its solvolytic reactivity only for five orders of
magnitude. The effect of the additional phenyl group is further
reduced to four order of magnitude for p-anysylmethyl derivative,
because of the strong electron-donating ability of the methoxy-
4
E
f
2.40
2.13
2
1
0
0.25
-0.63
-1
-2
-3
-4
-5
-6
-7
-0.96
-2.09
-4.63
X
OMe
Me
H
-6.03
-6.91
Cl
Figure 3. Comparison of the electrofugality of differently substituted
ferrocenylphenylmethyl cations 1 with the electrofugality of corresponding
benzhydryl and trityl cations.
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10.1002/ejoc.201801133
European Journal of Organic Chemistry
FULL PAPER
substituent on the phenyl ring by resonance. Drastic reduction of
the rate effect of the phenyl group to only two orders of
magnitude is found for the ferrocenylmethyl derivative (Scheme
3), indicating that the electron-donating ability of the α-ferrocenyl
group is significantly stronger than that of the p-tolyl and p-
anysyl groups. It appears that the stabilization caused by the
phenyl group is considerably leveled by a strong electron
releasing ability of the α-Fc group. Because of that, the electron
demand on the reaction center is reduced, resulting in small rate
enhancement caused by introduction of the phenyl group.
In line with the small effect of the phenyl group is small
impact of the substituents on the phenyl group on reactivity,
which is shown with a narrow range of electrofugalities of X-
substituted ferrocenylphenylmethyl electrofuges (Ef values from
1.30 to 2.40). Small effect of the substituents is nicely illustrated
with the Hammett-Brown plots in various solvents presented in
Figure 4. The absolute values of the ρ+ parameters in all
solvents used are in the range between 1.46 and 1.64, which
are in agreement with that obtained earlier at 0 °C in 80% aq.
acetone (ρ+ = –1.4).[4]
Also, due to strong electron-donating ability of the ferrocenyl
group, reduction of the positive charge on the reaction center in
the TS occurs. Both effects cause change of the reaction
constant (ρ+) in the same direction.
To enlighten the electronic effects that determine the
solvolytic behaviour of the substrates in more details, we
performed quantum-chemical calculations with carbocation
intermediates. Kinetic parameters for forward (heterolysis) and
backward (combination) reactions [5,7,11] show that the heterolytic
step in solvolysis of benzhydryl and ferrocenylphenylmethyl
derivatives considered here is distinctly endergonic. Hence,
according to Hammond postulate, the TS is carbocation-like, so
it is justified to analyze the electronic effects in carbocation
intermediate and imply that they are similar to those in TS.
Computational studies
There
are
two
previous
theoretical
studies
of
ferrocenylmethyl cations, both presenting the results that can
today be considered just qualitatively correct. In older one,
Gleiter and Seeger[ 15 ] have used modified Extended Hückel
method, and in the newer one, Borisov et al.[16] have used BLYP,
now outdated functional, and MP2, which in the case of parent
ferrocene does not perform well.[17 ] Moreover, partial atomic
charges reported in the second paper were calculated using
unreliable Mulliken population analysis.
logk
-1.8
OAc
Fe
-2.0
-2.2
-2.4
-2.6
-2.8
-3.0
-3.2
-3.4
-3.6
-3.7
X
Our intention was to compare the changes of partial charges
on carbocation center and its substituents as we go from
monosubstituted benzyl and ferrocenylmethyl carbocations to
100M
ρ+ = −1.52
90E10W
disubstituted
benzhydryl
and
ferrocenylphenylmethyl
ρ+ = −1.46
carbocations, both in vacuum and water. Based on comparison
of the existing experimental[18] and high-level computational[17,19]
data for ferrocene, we came to the conclusion that satisfactory
results can be obtained by using rung-five double-hybrid
functionals, like dispersion-corrected Grimme's B2PLYP-D3,[20]
in combination with medium-sized basis sets. The geometry
parameters obtained for the ferrocene molecule at B2PLYP-
D3/may-cc-pVTZ level of theory[21] are close to corresponding
experimental and CCSD(T) values. Calculated potential energy
difference between D5h and D5d ferrocene stationary points is 6
kJ/mol, which is close to 5 kJ/mol obtained at CCSD(T) level of
theory and to the experimental ferrocene internal rotation barrier
of 4 ± 1 kJ/mol.
As with the parent ferrocene, the eclipsed conformer of the
ferrocenylmethyl cation (Figure 5a) is a minimum on potential
energy surface, and the staggered one is the transition structure
for interconversion of two eclipsed conformers. Corresponding
threshold energy without the zero point energy correction and
the standard activation Gibbs energies at 298 K are 8 kJ/mol
and 10 kJ/mol, respectively.
80AN20W
ρ+ = −1.61
H
4-Cl
4-Br
80A20W
ρ+ = −1.64
3-F
3-Br 3-Cl
0.40
0.00
0.10
0.20
0.30
σ+
Figure 4. Hammett–Brown plots for the solvolysis of ferrocenylphenylmethyl
acetates in various solvents at 25°C. Binary solvents are given as (v/v). A =
acetone, AN = acetonitrile, E = ethanol, M = methanol, and W = water.
Since the Hammett-Brown ρ+ parameter can be taken here
as a measure for the charge “seen” by the aromatic ring at the
reaction center in the transition state, small absolute values of
the reaction constant (ρ+) in solvolysis of ferrocenylphenylmethyl
acetates indicate considerably reduced positive charge in the TS.
This can be rationalized with somewhat earlier transition state in
the heterolytic step of ferrocenylphenylmethyl acetates and/or
substantial delocalization of the positive charge generated in the
TS to α-Fc group. Ferrocenyl derivatives solvolyze faster than
the corresponding benzhydryl or trityl derivatives, so they
proceed via earlier, less carbocation-like transition states in
which the generation of the positive charge is less advanced.
The main feature of the ferrocenylmethyl cation is substantial
(45°) out-of plane bend of C−CH2 bond, bringing the CH2 carbon
to 2.15 Å from the Fe atom. Two cyclopentadiene (Cp) rings are
still planar, but inclined 15° to each other.
Structure of the ferrocenylphenylmethyl cation 1 (Figure 5b)
is similar to that of the ferrocenylmethyl cation. The ferrocene
moiety has also eclipsed conformation in which the CH2 group is
5
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10.1002/ejoc.201801133
European Journal of Organic Chemistry
FULL PAPER
half of phenyl group charge is transfered into the ferrocenyl
group.
a)
b)
In gas phase the positive charge in benzyl cation is
practically equally distributed between phenyl and CH2 groups.
By introducing another phenyl group and converting benzyl to
benzhydryl cation, gas-phase positive charge is also almost
evenly distributed between two phenyl groups and the CH group.
In water, the charge is somewhat higher on CH than on
individual phenyl groups. Substantial positive charge of the
phenyl groups in free benzhydryl cations indicates that the
phenyl groups have an inportant role in positive charge
stabilization. Consequently, the substituents on the phenyl ring
in benzhydryl derivatives influence the reactivity of the
substrates considerably, producing relatively large negative
Hammett-Brown reaction constants (ρ+ = –5.63)[4].
The charge distribution in ferrocenyl-substituted cations is
profoundly different. In ferrocenylmethyl cation most of the
positive charge (75 % in the gas phase and 73 % in the
continuum water, respectively) is delocalized to ferrocene moiety.
Similarly, in ferrocenylphenylmethyl cation 1, 65 % of the charge
in vacuum and 71 % in water is located on the ferrocenyl moiety,
indicating its high ability for accommodating positive charge. The
observation that only 11 % of the positive charge in vacuum and
6 % in water is delocalized to the phenyl group is quite
remarkable. Because of efficient accommodation of the positive
charge by the ferrocenyl group, i.e. its significant electron-
releasing ability into the empty p-orbital, the role of the phenyl
group in stabilization of the carbocation center is considerably
diminished.
Figure 5. B2PLYP-D3/may-cc-pVTZ optimized structures of (a)
ferrocenylmethyl and (b) ferrocenylphenylmethyl cations.
slightly more distant from the Fe atom (2.26 Å), and the angle
between two Cp planes is the same.
The electronic effects of the ferrocenyl group can be
analyzed by comparison of the charge distributions in ferrocenyl
electrofuges and in reference cations lacking the Fc group.
Therefore, beside ferrocenylmethyl and ferrocenylphenylmetyl
cations (presented in Figure 5), the geometries of benzyl and
benzhydryl cations were optimized at the same level of theory,
and the charges of cations were calculated using natural
population analysis (NPA). In Table 3 the NPA charges of the
carbocations (electrofuges) are compared. For each carbocation,
the partial charges of Ph and/or Fc groups, as well as of CH or
CH2 groups are given.
Although the NPA partial charges of the ferrocene moiety in
+
four examined compounds vary from 0.75 in Fc-CH2 to 0.50 in
+
Fc-CH-Ph-p-NH2 , partial charges of Fe atoms remain
remarkably constant (0.300-0.311), almost the same as in the
parent ferrocene (0.316). The rest of the positive charge is
divided almost evenly between the two Cp rings, though one
attached to the positive center bears on average 15 % more
charge than the other ring. The NPA charge distribution is
shown in Table S5 in the Supporting Information.
Table 3. Partial NPA charges in α-ferrocenyl cations and reference cations in
vacuum and water (in parentheses), calculated at B2PLYP-D3/may-cc-pVTZ
level of theory.
Partial natural population analysis charges
To quantify the influence of the ferrocenyl and substituted
phenyl groups on carbocation stability, we calculated hydrid ion
affinities (HIA) of several substituted ferrocenylphenylmethyl and
benzhydryl cations at B2PLYP-D3/may-cc-pVTZ level of theory
(Table 4; for details see Table S4 in the Supporting Information,).
Hydrid ion affinity of R+, HIA(R+), is defined as negative value of
standard reaction enthalpy of gas-phase reaction (2), and is
often used for comparison of carbocations intrinsic stabilities.[22]
Electrofuge
R1−CH−R2
+
q(R1)
(Ph/Fc)
q(R2)
(Ph)
q(CH/CH2)
+
Ph−CH2
0.520
(0.469)
0.480
(0.531)
(Benzyl cation)
Ph−CH−Ph +
(Benzhydryl cation)
0.310
(0.283)
0.380
(0.435)
0.310
(0.283)
R+(g) + H−(g) → R−H(g)
(2)
+
Fc−CH2
0.753
0.247
(Ferrocenylmethyl cation)
(0.727)
(0.273)
As the difference of HIA values equals to standard reaction
enthalpy of corresponding isodesmic reaction (3), it is much
more convenient to give HIA values relative to some referent
Fc−CH−Ph +
(Ferrocenylphenylmethyl
cation)
0.648
(0.706)
0.245
(0.235)
0.107
(0.059)
+
carbocation. We used benzyl carbocation, Ph-CH2 .
+
+
R1−H(g) + R2 (g) → R1 (g) + R2−H(g)
(3)
Upon transfer to water, partial charges on CH/CH2 groups of
all cations somewhat increase, i.e. become more localized,
except in the most stable ferrocenylphenylmethyl cation. In the
latter the charge on CH group remains almost the same, while
In line with experimental findings is the impact of the
substituents on the phenyl ring on stability of the benzhydryl
cation and ferrocenylphenylmethyl cation. The p-amino group,
which is
a
strong electron-donating group, stabilizes the
6
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10.1002/ejoc.201801133
European Journal of Organic Chemistry
FULL PAPER
benzhydryl cation for 17 kcal/mol in gas phase and 15 kcal in
water, while the electron-accepting p-nitro group, destabilizes it
for 11 kcal/mol in gas phase and 6 kcal/mol in water. On the
other hand, stabilization effect of the substituents in
ferrocenylphenylmethyl cation is much less pronounced. Thus,
NH2 group stabilizes the ferrocenylphenylmethyl cation for only 6
kcal/mol in gas phase and 2 kcal/mol in water, while NO2 group
destabilizes it for 8 kcal/mol in gas phase and only 1 kcal/mol in
water.
relative stabilities of the cations (Table 4) and the distribution of
the positive charge in the ferrocenyl cations (Table 3) obtained
computationally are consistent with large enhancement of the
solvolytic reactivity of ferrocenylphenylmethyl derivatives in
comparison to benzhydryl derivatives, with diminished effect of
the phenyl ring and also with small rate effects of the
substituents on the phenyl ring. The latter is illustrated with
narrow
range
of
electrofugalities
of
X-substituted
ferrocenylphenylmethyl cations (Table 2) as well as with small
absolute ρ+ constants, both experimental and calculated.
Table 4. Hydrogen ion affinities (HIA) and corresponding standard
reaction Gibbs energies in vacuum and water relative to benzyl cation,
calculated at B2PLYP-D3/may-cc-pVTZ level of theory (in kcal/mol).
Experimental Section
Cation
HIA(g)rel
ΔrG°(g)rel
ΔrG°(H2O)rel
Substrate Preparation
+
4-Methoxy-4'-methylbenzhydryol and 4-methoxy-4'-phenoxybenzhydryol
were prepared according to the procedure described earlier,23 as well as
(2,3-dihydrobenzofuran-5-yl)(4-methoxyphenyl)methanol and bis(2,3-
dihydrobenzofuran-5-yl)methanol.24 The ferrocenyl phenyl ketones were
prepared by standard acylation using the corresponding benzoyl chloride
and ferrocene in dichloromethane with AlCl3 as catalyst at low (0 °C) or
ambient temperature. 25 Reduction of ferrocenyl phenyl ketones with
LiAlH4 in diethyl ether according to known procedure gave 3,5-
dichlorophenylferrocenmethanol (63%), 3-chlorophenylferrocenmethanol
C6H5CH2
0.0
0.0
0.0
−22.3
11.3
+
+
4-NH2C6H4CH2
−26.6
−26.2
4-NO2C6H4CH2
16.3
16.1
+
C6H5CHC6H5
−24.0[a]
−41.1[a]
−12.4[a]
−41.5
−24.0[b]
−40.7[b]
−12.9[b]
−41.8
−14.1
−28.9
−7.9
+
+
4-NH2C6H4CHC6H5
(80%),
fluorophenylferrocenylmethanol (85%), 4-chlorophenylferrocenmethanol
(76%), 4-bromophenylferrocenmethanol (66%), and
phenylferrocenmethanol (81%), respectively.26
3-bromophenylferrocenmethanol
(85%),
3-
4-NO2C6H4CHC6H5
+
FcCH2
−34.4
−39.1
−41.2
−38.1
C6H5FcCH+
−49.3[a]
−55.7[a]
−42.4[a]
−50.0[b]
−56.2[b]
−42.3[b]
General Procedure for the Synthesis of Benzhydryl and
Ferrocenylphenylmethyl Acetates: A solution of acetyl chloride (2 eq)
in anhydrous benzene (7 mL) was added dropwise to a previously
prepared stirred solution of the appropiate benzhydrol or
phenylferrocenylethanol (1 eq) and pyridine (0.5 g, 6.32 mmol) in
anhydrous benzene (7 mL). The reaction mixture was stirred under argon
at ambient temperature for 1-2 h. Precipitated pyridinium chloride was
removed by filtration, and excess of pyridine was removed with
hydrochloride acid (3%). The benzene layer was separated and washed
with water. After drying over anhydrous sodium sulfate, benzene was
evaporated in vacuum. Acetates were obtained as pale yellow
(benzhydryl acetates) or dark red (ferrocenylphenylmethyl acetates)
crystals or oils (yield 48.1-84.9 %).
4-NH2C6H4FcCH +
4-NO2C6H4FcCH +
[a] Absolute HIA values (hydrogen iona affinities) of parent RH molecules were
calculated by adding the scaled ωB97X-D/may-cc-pVTZ thermal corrections to
B2PLYP-D3/may-cc-pVTZ potential energies. [b] Absolute gas-phase standard
Gibbs energies of parent RH molecules were calculated by adding the scaled
ωB97X-D/may-cc-pVTZ thermal corrections to B2PLYP-D3/may-cc-pVTZ
potential energies.
Plotting the relative standard reaction Gibbs energies in
water at 298 K divided by RTln(10) for ferrocenylphenylmethyl,
4-Methoxy-4'-methylbenzhydryl Acetate:[12] This compound was
obtained from 4-methoxy-4'-methylbenzhydrol (0.3 g, 1.31 mmol),
pyridine (0.3 g, 3.79 mmol), and acetyl chloride (0.12 g, 1.56 mmol); yield
0.17 g, 48.1 %. 1H NMR (400 MHz, CDCl3, 25°C): δ/ppm = 2.12 (s, 3H;
CH3COOR), 2.32 (s, 3H; CH3), 3.77 (s, 3H; OCH3), 6.82-6.86 (s, 3H;
ArCHAr + Ar), 7.12-7.26 (m, 6H; Ar-CH3 + Ar-OCH3). 13C NMR (100 MHz,
CDCl3, 25°C): δ/ppm = 21.17 (CH3COOR), 21.35 (CH3), 55.28 (OCH3),
76.56 (ArCHAr), 113.91, 126.96, 128.62, 123.56, 129.19, 132.69, 137.53,
159.30 (Ar-CH3 + Ar-OCH3), 170.10 (COOR).
ferrocenyl-p-NH2-phenylmethyl
and
ferrocenyl-p-NO2-
phenylmethyl cations against σ+, gives a very good Hammett-
Brown correlation (R2 = 0.997) with reaction constant ρ+ = −1.08
± 0.06. Remarkably, this −ρ+ is only slightly smaller than the
experimental −ρ+ values obtained in solvents less polar than
water (−1.46 to −1.64; Figure 4). Having in mind that the
standard Gibbs energies refer to formation of free cations, such
good agreement with the experimental results might be an
indication that ferrocenylphenylmethyl derivatives, indeed,
solvolyze via late carbocation-like transition states.
4-Methoxy-4'-phenoxybenzhydryl Acetate:[12] This compound was
obtained from 4-methoxy-4'-phenoxybenzhydrol (0.5 g, 1.63 mmol),
pyridine (0.3 g, 3.79 mmol), and acetyl chloride (0.24 g, 3.16 mmol); yield
0.30 g, 52.8 %. 1H NMR (400 MHz, CDCl3, 25°C): δ/ppm = 2.13 (s, 3H;
CH3COOR), 3.77 (s, 3H; OCH3), 6.84 (s, 1H; ArCHAr), 6.86-7.34 (m,
13H; Ar-OC6H5 + Ar-OCH3). 13C NMR (100 MHz, CDCl3, 25°C): δ/ppm =
21.41 (CH3COOR), 55.37 (OCH3), 76.27 (ArCHAr), 114.03, 118.66,
119.21, 123.56, 128.62, 128.63, 129.87, 132.54, 135.33, 157.03, 157.06,
159.43 (Ar-OC6H5 + Ar-OCH3), 170.12 (COOR).
Conclusions
Experimental results are in accord with quantum chemical
calculations, all indicating profound electron-releasing ability of
the ferrocenyl group into the adjacent empty p-orbital. Both the
7
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10.1002/ejoc.201801133
European Journal of Organic Chemistry
FULL PAPER
(2,3-dihydrobenzofuran-5-yl)(4-methoxyphenyl)methyl
(C5H5), 73.71 (ArCHFc), 87.51 (Fc), 114.18 (d, J = 22.2 Hz; Ar), 115.03
(d, J = 21.2 Hz; Ar), 123.00 (d, J = 2.9 Hz; Ar), 129.91 (d, J = 8.1 Hz; Ar),
142.73 (d, J = 7.1 Hz, Ar), 162.76 (d, J = 246.0 Hz; Ar), 170.08 (COOR).
Collection of HRMS data or elemental analysis were not accessible for
this compound, due to its limited stability.
Acetate:[27]This compound was obtained from (2,3-dihydrobenzofuran-5-
yl)(4-methoxyphenyl)methanol (0.2 g, 0.78 mmol), pyridine (0.3 g, 3.79
mmol), and acetyl chloride (0.12 g, 1.56 mmol); yield 0.17 g, 73.1 %. 1H
NMR (400 MHz, CDCl3, 25°C): δ/ppm = 2.12 (s, 3H; CH3COOR), 3.16 (t,
J = 8.7 Hz, 2H; OCH2CH2), 3.78 (s, 3H; OCH3), 4.54 (t, J = 8.7 Hz, 2H;
OCH2), 6.79 (s, 1H; ArCHAr), 6.73-7.26 (m, 7H; Ar-Fur + Ar-OCH3). 13C
NMR (100 MHz, CDCl3, 25°C): δ/ppm = 21.51 (CH3COOR), 29.77
(OCH2CH2), 55.38 (OCH3) 71.51 (OCH2), 76.67 (ArCHAr), 109.17,
113.93, 124.11, 127.41, 128.39, 128.45, 132.74, 132.91, 159.24, 159.93
(Ar-Fur + Ar-OCH3), 170.25 (COOR).
4-Chlorophenylferrocenylmethyl Acetate: This compound was
obtained from 4-chlorophenylferrocenmethanol (0.5 g, 1.52 mmol),
pyridine (0.5 g, 6.32 mmol), and acetyl chloride (0.24 g, 3.04 mmol); yield
0.44 g, 77.6 %, m. p. 83-85 °C. 1H NMR (400 MHz, CDCl3, 25°C): δ/ppm
= 2.11 (s, 3H; CH3COOR), 4.11 (s, 5H; C5H5), 3.99-4.31 (m, 4H; C5H4),
6.70 (s, 1H; ArCHFc), 7.32-7.37 (m, 4H; Ar). 13C NMR (100 MHz, CDCl3,
25°C): δ/ppm = 21.36 (CH3COOR), 67.56, 67.75, 68.43, 68.62 (C5H4),
68.98 (C5H5), 73.75 (ArCHFc), 87.56 (Fc), 128.57, 128.72, 133.87,
138.75 (Ar), 170.04 (COOR). HRMS (MALDI TOF/TOF); calculated for
C19H17ClFeO2 [M]+ 368.0267; found 368.0276.
Bis(2,3-dihydrobenzofuran-5-yl)methyl Acetate:[27] This compound
was obtained from bis(dihydrofuranyl)benzhydrol (0.2 g, 0.75 mmol),
pyridine (0.3 g, 3.79 mmol), and acetyl chloride (0.12 g, 1.56 mmol); yield
0.18 g, 77.3 %. 1H NMR (400 MHz, CDCl3, 25°C): δ/ppm = 2.13 (s, 3H;
CH3COOR), 3.16 (t, J = 8.7 Hz, 4H; OCH2CH2), 4.54 (t, J = 8.7 Hz, 4H;
OCH2), 6.73 (d, J = 8.2 Hz, 2H; Ar), 6.77 (s, 1H; ArCHAr), 7.07-7.15 (m,
4H; Ar). 13C NMR (100 MHz, CDCl3, 25°C): δ/ppm = 21.50 (CH3COOR),
29.75 (OCH2CH2), 71.46 (OCH2), 76.93 (ArCHAr), 109.12, 123.95,
127.20, 127.36, 132.88, 159.86 (Ar), 170.17 (COOR).
4-Bromophenylferrocenylmethyl Acetate: This compound was
obtained from 4-bromophenylferrocenmethanol (0.5 g, 1.34 mmol),
pyridine (0.5 g, 6.32 mmol), and acetyl chloride (0.21 g, 2.68 mmol); yield
0.39 g, 70.1 %, m. p. 85-86 °C. 1H NMR (400 MHz, CDCl3, 25°C): δ/ppm
= 2.11 (s, 3H; CH3COOR), 4.10 (s, 5H; C5H5), 3.97-4.30 (m, 4H; C5H4),
6.67 (s, 1H; ArCHFc), 7.29 (d, 2H, J = 8.4 Hz; Ar), 7.48 (d, 2H, J = 8.4
Hz; Ar). 13C NMR (100 MHz, CDCl3, 25°C): δ/ppm = 21.38 (CH3COOR),
67.56, 67.75, 68.44, 68.65 (C5H4), 68.99 (C5H5), 73.80 (ArCHFc), 87.43
(Fc), 122.05, 129.03, 131.52, 139.22 (Ar), 170.06 (COOR). Collection of
HRMS data or elemental analysis were not accessible for this compound,
due to its limited stability.
3,5-Dichlorophenylferrocenylmethyl Acetate: This compound was
obtained from 3,5-dichlorophenylferrocenmethanol (0.2 g, 0.55 mmol),
pyridine (0.5 g, 6.32 mmol), and acetyl chloride (0.09 g, 1.1 mmol); yield
0.16 g, 71.7 %, m. p. 115-116 °C. 1H NMR (400 MHz, CDCl3, 25°C):
δ/ppm = 2.15 (s, 3H; CH3COOR), 4.01-4.28 (m, 4H; C5H4), 4.12 (s, 5H;
C5H5), 6.61 (s, 1H; ArCHFc), 7.28 (m, 3H; Ar). 13C NMR (100 MHz,
CDCl3, 25°C): δ/ppm = 21.30 (CH3COOR), 67.48, 67.52, 68.60, 68.76
(C5H4), 69.08 (C5H5), 73.15 (ArCHFc), 87.16 (Fc), 125.79, 128.25,
135.00, 143.70 (Ar), 169.90 (COOR). Collection of HRMS data or
elemental analysis were not accessible for this compound, due to its
limited stability.
Ferrocenylphenylmethyl Acetate: This compound was obtained from
phenylferrocenmethanol (0.5g, 1.7 mmol), pyridine (0.5 g, 6.32 mmol),
and acetyl chloride (0.27 g, 3.40 mol); yield 0.44 g, 77.1 %, m. p. 78-
80 °C. 1H NMR (400 MHz, CDCl3, 25°C): δ/ppm
= 2.10 (s, 3H;
CH3COOR), 4.09 (s, 5H; C5H5), 4.01-4.33 (m, 4H; C5H4), 6.73 (s, 1H;
ArCHFc), 7.29-7.42 (m, 5H; Ar). 13C NMR (100 MHz, CDCl3, 25°C):
δ/ppm = 21.43 (CH3COOR), 67.68, 67.87, 68.28, 68.45 (C5H4), 68.93
(C5H5), 74.38 (ArCHFc), 87.94 (Fc), 127.31, 128.07, 128.32, 140.10 (Ar),
170.12 (COOR). Collection of HRMS data or elemental analysis were not
accessible for this compound, due to its limited stability.
3-Chlorophenylferrocenylmethyl Acetate: This compound was
obtained from 3-chlorophenylferrocenmethanol (0.5 g, 1.52 mmol),
pyridine (0.5 g, 6.32 mmol), and acetyl chloride (0.24 g, 3.04 mmol); yield
0.48 g, 84.9 %, m. p. 123-125 °C. 1H NMR (400 MHz, CDCl3, 25°C):
δ/ppm = 2.13 (s, 3H; CH3COOR), 4.01-4.30 (m, 4H; C5H4), 4.11 (s, 5H;
C5H5), 6.67 (s, 1H; ArCHFc), 7.28-7.41 (m, 4H; Ar). 13C NMR (100 MHz,
CDCl3, 25°C): δ/ppm = 21.37 (CH3COOR), 67.59, 67.70, 68.46, 68.62
(C5H4), 69.01 (C5H5), 73.72 (ArCHFc), 87.53 (Fc), 125.50, 127.40,
128.26, 129.68, 134.27, 142.25 (Ar), 170.05 (COOR). HRMS (MALDI
TOF/TOF); calculated for C19H17Cl FeO2 [M]+ 368.0267; found 368.0251.
General Procedure for the Synthesis of Ferrocenylphenylmethyl
Benzoates: A solution of benzoyl chloride (2 eq) in anhydrous benzene
(8 mL) was added dropwise to a previously prepared stirred solution of
the appropiate phenylferrocenylmethanol (1 eq) and pyridine (0.5 g, 6.32
mmol) in anhydrous benzene (8 mL). The reaction mixture was stirred
under argon at ambient temperature for 24 h. Precipitated pyridinium
chloride was removed by filtration, and excess of pyridine was removed
with hydrochloride acid (5%). The benzene layer was separated and
washed with water. After drying over anhydrous sodium sulfate, benzene
was evaporated in vacuum. Benzoates were obtained as dark red
crystals or oils (yield 70.1-84.9 %).
3-Bromophenylferrocenylmethyl Acetate: This compound was
obtained from 3-bromophenylferrocenmethanol (0.5 g, 1.34 mmol),
pyridine (0.5 g, 6.32 mmol), and acetyl chloride (0.21 g, 2.68 mmol); yield
0.43 g, 77.6 %, m. p. 114-115 °C. 1H NMR (400 MHz, CDCl3, 25°C):
δ/ppm = 2.13 (s, 3H; CH3COOR), 4.00-4.30 (m, 4H; C5H4), 4.11 (s, 5H;
C5H5), 6.66 (s, 1H; ArCHFc), 7.20-7.57 (m, 4H; Ar). 13C NMR (100 MHz,
CDCl3, 25°C): δ/ppm = 21.40 (CH3COOR), 67.59, 67.72, 68.47, 68.64
(C5H4), 69.02 (C5H5), 73.65 (ArCHFc), 87.51 (Fc), 122.42, 125.96,
129.97, 130.31, 131.19, 142.46 (Ar), 170.04 (COOR). HRMS (MALDI
TOF/TOF); calculated for C19H17BrFeO2 [M]+ 411.9761; found 411.9751.
3,5-Dichlorophenylferrocenylmethyl Benzoate: This compound was
obtained from 3,5-dichlorophenylferrocenmethanol (0.3 g, 0.83 mmol),
pyridine (0.5 g, 6.32 mmol), and benzoyl chloride (0.26 g, 1.85 mmol);
yield 0.21 g, 54.2 %. 1H NMR (400 MHz, CDCl3, 25°C): δ/ppm = 4.13 (s,
5H; C5H5), 4.13-4.40 (m, 4H; C5H4), 6.86 (s, 1H; ArCHFc), 7.27-8.16 (m,
8H; Ar + Ar-Cl2). 13C NMR (100 MHz, CDCl3, 25°C): δ/ppm = 67.10,
67.60, 68.56, 68.74 (C5H4), 69.12 (C5H5), 73.62 (ArCHFc), 87.45 (Fc),
123.83, 125.72, 128.31, 128.75, 129.93, 130.00, 133.54, 143.90 (Ar + Ar-
Cl2), 165.47 (COOR). HRMS (MALDI TOF/TOF); calculated for
C24H18Cl2FeO2 [M]+ 464.0034; found 464.0036.
3-Fluorophenylferrocenylmethyl Acetate: This compound was
obtained from 3-fluorophenylferrocenmethanol (0.5 g, 1.60 mmol),
pyridine (0.5 g, 6.32 mmol), and acetyl chloride (0.25 g, 3.20 mmol); yield
0.48 g, 84.7 %, m. p. 113-115 °C. 1H NMR (400 MHz, CDCl3, 25°C):
δ/ppm = 2.13 (s, 3H; CH3COOR), 4.02-4.30 (m, 4H; C5H4), 4.11 (s, 5H;
C5H5), 6.69 (s, 1H; ArCHFc), 6.97-7.36 (m, 4H; Ar). 19F NMR (376 MHz,
CDCl3, 25°C): δ/ppm = -112.80 (m). 13C NMR (100 MHz, CDCl3, 25°C):
δ/ppm = 21.39 (CH3COOR), 67.60, 67.69, 68.43, 68.62 (C5H4), 69.01
8
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10.1002/ejoc.201801133
European Journal of Organic Chemistry
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3-Chlorophenylferrocenylmethyl Benzoate: This compound was
obtained from 3-chlorophenylferrocenmethanol (0.3 g, 0.91 mmol),
pyridine (0.5 g, 6.32 mmol), and benzoyl chloride (0.26 g, 1.85 mmol);
yield 0.419 g, 48.1 %, m. p. 86-88 °C. 1H NMR (400 MHz, CDCl3, 25°C):
δ/ppm = 4.11 (s, 5H; C5H5), 4.12-4.40 (m, 4H; C5H4), 6.92 (s, 1H;
ArCHFc), 7.26-8.15 (m, 9H; Ar + Ar-Cl). 13C NMR (100 MHz, CDCl3,
25°C): δ/ppm = 67.32, 67.64, 68.40, 68.58 (C5H4), 69.04 (C5H5), 74.17
(ArCHFc), 87.82 (Fc), 125.41, 127.30, 128.30, 128.64, 129.75, 129.87,
130.18, 133.36, 134.30, 142.43 (Ar + Ar-Cl), 165.54 (COOR). HRMS
(MALDI TOF/TOF); calculated for C24H19ClFeO2 [M]+ 430.0424; found
430.0439.
Ar). 13C NMR (100 MHz, CDCl3, 25°C): δ/ppm = 67.57, 67.76, 68.25,
68.44 (C5H4), 69.00 (C5H5), 74.93 (ArCHFc), 88.34 (Fc), 127.25, 128.14,
128.44, 128.55, 129.85, 130.48, 133.17, 140.36 (Ar), 165.68 (COOR).
HRMS (MALDI TOF/TOF); calculated for C24H20FeO2 [M]+ 396.0813;
found 396.0806.
Kinetic Methods: Solvolysis rate constants were measured titrimetrically
by means of TIM 856 titration manager (Radiometer Analytical SAS
Villeurbanne Cedex, France), using a Red Rod Ag/AgCl combined pH
electrode. Typically, 20-50 mg of the acetate or benzoate was dissolved
in 0.10-0.20 mL of dichloromethane, and injected into the solvent that
was thermostated at the required temperature (± 0.01 °C). The liberated
acid was continuously titrated at pH = 7.20-7.80 by using a 0.016 M or
0.032 M solution of sodium hydroxide in appropriate solvent. Individual
rate constants were obtained by the least-squares fitting of data to the
first-order kinetic equation for three to four half-lives. The rate constants
were averaged from at least three measurements.
3-Bromophenylferrocenylmethyl Benzoate: This compound was
obtained from 3-bromophenylferrocenmethanol (0.3 g, 0.8 mmol),
pyridine (0.5 g, 6.32 mmol), and benzoyl chloride (0.23 g, 1.63 mmol);
yield 0.19 g, 49.5 %. 1H NMR (400 MHz, CDCl3, 25°C): δ/ppm = 4.11 (s,
5H; C5H5), 4.16-4.40 (m, 4H; C5H4), 6.90 (s, 1H; ArCHFc), 7.19-8.15 (m,
9H; Ar + Ar-Br). 13C NMR (100 MHz, CDCl3, 25°C): δ/ppm = 67.33, 67.62,
68.40, 68.58 (C5H4), 69.03 (C5H5), 74.10 (ArCHFc), 87.80 (Fc), 122.46,
125.86, 128.63, 129.85, 130.04, 130.15, 130.21, 131.21, 133.35, 142.65
(Ar + Ar-Br), 165.52 (COOR). HRMS (MALDI TOF/TOF); calculated for
C24H19BrFeO2 [M]+ 473.9918; found 473.9916.
Calculation methods: All calculations were performed with Gaussian 16,
rev. A.03,[28] using SMD continuum solvation[29] method for modeling
solvent effects. Geometries of all involved species were fully optimized
and confirmed as minima by absence of imaginary frequencies. The NPA
partial charges were calculated with NBO 6.0 program package.30 After
trying different functionals and different basis sets, Grimme's double-
hybrid B2PLYP-D3 functional[20] with Dunning's all-electrons may-cc-
pVTZ triple zeta basis set[21] were selected for the final calculations. In
several cases, gas-phase thermal corrections were calculated with faster
ωB97X-D functional[31] and the same basis set, scaled, and added to
B2PLYP-D3 gas-phase energies.
3-Fluorophenylferrocenylmethyl Benzoate: This compound was
obtained from 3-fluorophenylferrocenmethanol (0.3 g, 0.96 mmol),
pyridine (0.5 g, 6.32 mmol), and benzoyl chloride (0.27 g, 1.92 mmol);
yield 0.22 g, 55.2 %, m. p. 66-68 °C. 1H NMR (400 MHz, CDCl3, 25°C):
δ/ppm = 4.10 (s, 5H; C5H5), 4.11 - 4.41 (m, 4H; C5H4), 6.94 (s, 1H;
ArCHFc), 6.98-8.15 (m, 9H; Ar + Ar-F). 19F NMR (376 MHz, CDCl3,
25°C): δ/ppm = -112.62 (m). 13C NMR (100 MHz, CDCl3, 25°C): δ/ppm =
67.65, 67.31, 68.36, 68.57(C5H4), 69.04 (C5H5), 74.17 (ArCHFc), 87.85
(Fc), 114.09 (d, J = 22.2 Hz; Ar-F), 115.05 (d, J = 21.1 Hz; Ar-F), 122.88
(d, J = 2.9 Hz; Ar-F), 129.98 (d, J = 8.2 Hz; Ar-F), 142.93 (d, J = 7.1 Hz;
Ar-F), 162.77 (d, J = 246.2 Hz; Ar-F), 128.63, 129.85, 130.20, 133.34 (Ar),
165.56 (COOR). HRMS (MALDI TOF/TOF); calculated for C24H19FFeO2
[M]+ 414.0719; found 414.0706.
Acknowledgements
The authors gratefully acknowledge financial support of this
research by the Croatian Science Foundation (under the project
number IP-1021).
4-Chlorophenylferrocenylmethyl Benzoate: This compound was
obtained from 4-chlorophenylferrocenmethanol (0.3 g, 0.91 mmol),
pyridine (0.5 g, 6.32 mmol), and benzoyl chloride (0.26 g, 1.85 mmol);
yield 0.22 g, 55.6 %, m. p. 99-101 °C. 1H NMR (400 MHz, CDCl3, 25°C):
δ/ppm = 4.10 (s, 5H; C5H5), 4.15-4.40 (m, 4H; C5H4), 6.93 (s, 1H;
ArCHFc), 7.31-8.13 (m, 9H; Ar + Ar-Cl). 13C NMR (100 MHz, CDCl3,
25°C): δ/ppm = 67.42, 67.62, 68.38, 68.59 (C5H4), 69.03 (C5H5), 74.24
(ArCHFc), 87.87 (Fc), 128.61, 128.63, 128.65, 129.83, 130.25, 133.32,
133.91, 138.95 (Ar + Ar-Cl), 165.56 (COOR). HRMS (MALDI TOF/TOF);
calculated for C24H19ClFeO2 [M]+ 430.0424; found 430.0442.
Keywords: electrofugality • α-ferrocenyl group • substituent
effect • solvolysis • ferrocenylphenylmethyl cation
4-Bromophenylferrocenylmethyl Benzoate: This compound was
obtained from 4-bromophenylferrocenmethanol (0.3 g, 0.8 mmol),
pyridine (0.5 g, 6.32 mmol), and benzoyl chloride (0.23 g, 1.63 mmol);
yield 0.22 g, 57.3 %, m. p. 88-90 °C. 1H NMR (400 MHz, CDCl3, 25°C):
δ/ppm = 4.11 (s, 5H; C5H5), 4.18-4.40 (m, 4H; C5H4), 6.91(s, 1H;
ArCHFc), 7.35-8.13 (m, 9H; Ar + Ar-Br). 13C NMR (100 MHz, CDCl3,
25°C): δ/ppm = 67.41, 67.62, 68.38, 68.60 (C5H4), 69.02 (C5H5), 74.28
(ArCHFc), 87.77 (Fc), 122.09, 128.61, 128.94, 129.82, 130.22, 131.59,
133.32, 139.45(Ar), 165.58 (COOR). HRMS (MALDI TOF/TOF);
calculated for C24H19BrFeO2 [M]+ 473.9918; found 473.9925.
Ferrocenylphenylmethyl Benzoate: This compound was obtained from
phenylferrocenmethanol (0.3g, 1.02 mmol), pyridine (0.5 g, 6.32 mmol),
and benzoyl chloride (0.29 g, 2.04 mol); yield 0.21 g, 51.7 %, m. p. 99-
101 °C. 1H NMR (400 MHz, CDCl3, 25°C): δ/ppm = 4.10 (s, 5H; C5H5),
4.12-4.42 (m, 4H; C5H4), 6.97 (s, 1H; ArCHFc), 7.28-8.15 (m, 10H; Ar +
9
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10.1002/ejoc.201801133
European Journal of Organic Chemistry
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European Journal of Organic Chemistry
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FULL PAPER
Electrofugalities of the series of
ferrocenyl-X-phenyl methyl cations
showed that their values are about
eight units higher than those of the
corresponding benzhydryl cations,
and also that all fell in a narrow range
of reactivities. Calculations at
B2PLYP-D3/may-cc-pVTZ level
established a profound electron-
releasing ability of the ferrocenyl
group into the empty p-orbital, which
stabilizes the solvolytic TS and levels
the effects of other groups.
Effect of the α-ferrocenyl group
Marijan Marijan, Sandra Jurić, Zlatko
Mihalić, Olga Kronja*
Page No. – Page No.
Impact of the α-Ferrocenyl Group on
Solvolytic Reactivity − Electrofugality
of Ferrocenylphenylmethyl Cations
11
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