Electrophilicity parameters for 2-benzylidene-indan-1,3-diones - A systematic extension of the benzhydrylium based electrophilicity scale

Article abstract of DOI:10.1039/b708025e

Kinetics of the reactions of four 2-benzylidene-indan-1,3-diones (1a-d) with carbanions (2a-l) have been studied photometrically in dimethyl sulfoxide solution at 20 °C, and the electrophilicity parameters E were determined by the linear free energy relat

Full text of DOI:10.1039/b708025e

View Article Online / Journal Homepage / Table of Contents for this issue
PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Electrophilicity parameters for 2-benzylidene-indan-1,3-diones—a systematic
extension of the benzhydrylium based electrophilicity scale†
Stefan T. A. Berger, Florian H. Seeliger, Florian Hofbauer and Herbert Mayr*
Received 29th May 2007, Accepted 23rd July 2007
First published as an Advance Article on the web 9th August 2007
DOI: 10.1039/b708025e
Kinetics of the reactions of four 2-benzylidene-indan-1,3-diones (1a–d) with carbanions (2a–l) have
been studied photometrically in dimethyl sulfoxide solution at 20 ◦C, and the electrophilicity
parameters E were determined by the linear free energy relationship log k2(20 ◦C) = s(N + E) (eqn (1)).
The rate-determining step of these reactions is the nucleophilic attack of the carbon nucleophile at the
double bond of the Michael acceptor. Comparisons with literature data show that the linear free energy
relationship (eqn (1)) allows the semiquantitative prediction of the reactivities of
2-benzylidene-indan-1,3-diones towards various nucleophiles.
Introduction
Numerous kinetic investigations have shown that the rate con-
stants for the reactions of carbocations with nucleophiles can be
described by eqn (1).1–4
log k2(20 ◦C) = s(N + E)
(1)
Therein, k2 corresponds to the second-order rate constant in L
mol−1 s−1, s to the nucleophile-specific slope parameter, N to the
nucleophilicity parameter, and E to the electrophilicity parameter.
By using benzhydrylium ions and quinone methides as reference
electrophiles,5 it became possible to compare the reactivities of
numerous r-, n- and p-nucleophiles in a single scale.
For the characterization of many synthetically important nucle-
ophiles, for example stabilized carbanions and amines, reference
electrophiles with −10 > E > −16 were needed. Because this range
is presently only covered by the quinone methides 1i and 1j (Fig. 1),
which are difficult to synthesize, we were looking for more readily
accessible alternatives.
Fig. 1 Correlation of (log k2)/s with the nucleophilicity parameter N for
the reactions of the benzhydrylium ion 1h and the quinone methides 1i–k
with carbanions (DMSO, 20 ◦C, from ref. 5).
Lemek showed that eqn (1) is also applicable to reactions of
nucleophiles with ordinary Michael acceptors, e.g., benzylidene-
malononitriles.6 We, therefore, expected a similar behavior of
the easily producible 2-benzylidene-indan-1,3-diones 1a–d, which
have previously been investigated in medical and material
chemistry.7 Some derivatives show antibacterial activities or non-
linear optical properties, some have been used as electrolumines-
cent devices, or as eye lens clarification agents.7 The 2-benzylidene-
indan-1,3-diones can be considered as organic Lewis acids.8
Because of their low-lying LUMOs they are reactive Michael
acceptors and have been used as heterodienes in cycloaddition
reactions.9
Due to the fact that the double bonds of the 2-benzylidene-
indan-1,3-diones are strongly polarized by the mesomeric electron-
withdrawing effect of the carbonyl groups, the double bond is
highly electrophilic and can be attacked by many nucleophiles.
Zalukaevs and Anokhina showed that the reaction of 2-benzyl-
idene-indan-1,3-dione with ethyl acetoacetate gives the corre-
ponding Michael adduct.10 In the reactions of 2-benzylidene-
indan-1,3-diones with acetylacetone, ethyl acetoacetate, diethyl
malonate, and phenylacetophenone, Michael adducts were ob-
tained, which undergo consecutive reactions.11 Additions of
arylnitromethanes,12 dimedone imines,13 di-, and trialkylphos-
phites,14 and of phosphonium ylides14b,14c have also been described.
Recently, hydride transfer from the Hantzsch ester to a benzyl-
idene-indan-1,3-dione derivative has been observed.15
We now report on the kinetics of the additions of the stabilized
carbanions 2a–l (Table 1) to the 2-benzylidene-indan-1,3-diones
1a–d in DMSO and show that the second-order rate constants
k2 can be described by eqn (1). The results will then be compared
with Bernasconi’s rate constants for the reactions of 2-benzylidene-
indan-1,3-dione 1d with amines in DMSO–H2O (50 : 50 v,v).16
Department Chemie und Biochemie, Ludwig-Maximilians-Universita¨t,
Butenandtstr. 5-13 (Haus F), 81377 Mu¨nchen, Germany. E-mail:
herbert.mayr@cup.uni-muenchen.de; Fax: +49-89-2180-77717; Tel: +49-
89-2180-77719
† Electronic supplementary information (ESI) available: Preparation and
characterization (NMR) of products 3 and details of the kinetic measure-
ments. See DOI: 10.1039/b708025e
3020 | Org. Biomol. Chem., 2007, 5, 3020–3026
This journal is
The Royal Society of Chemistry 2007
©

View Article Online
Table 1 N- and s-parameters of the employed nucleophiles in DMSO
Table 2 Characterized Michael adducts 3− or 3 and some characteristic
1H NMR chemical shifts and coupling constants
Nucleophile
N
s
Reactants
Adducts
d(Ha)/ppm
d(Hb)/ppm
J/Hz
2a
2b
2c
13.91a
0.86a
1a
1a
1a
1b
1b
1c
1c
1d
2d
2h
2l
2h
2k
2d
2h
2d
3ad−
3ah−
3al
5.23
4.16
3.98
dsa
4.17
4.33b
4.34
4.24
4.40
12.4
11.6
dsa
5.76
dsa
3bh−
3bk
5.81
11.3
16.27a
16.96b
0.77a
0.73b
5.03/5.31b
5.28
b
3cd−
3ch−
3dd−
12.3
11.4
12.3
5.85
5.35
a Diastereomers, double sets of signals in the ratio 2 : 1 have been found
(see ESI†). b d = 4.33 (dt, 3J = 7.7 Hz, 3J = 3.9 Hz, 1 H), 5.03 (dd, 2J =
13.3 Hz, 3J = 7.4 Hz, 1 H), 5.31 (dd, 2J = 13.3 Hz, 3J = 8.5 Hz, 1H).
2d
2e
2f
17.64a
18.82a
18.67c
0.73a
0.69a
0.68c
Reaction products
The anionic adducts 3− obtained by mixing equimolar amounts of
the Michael acceptors 1 and the potassium salts of the carbanions
2 in d6-DMSO solutions were investigated by NMR spectroscopy.
In few cases, the products 3 obtained after protonation of 3−
were isolated and characterized (Scheme 2). Because for other
combinations of the electrophiles 1a–d with the nucleophiles 2a–
l, analogous reaction products were expected, products have not
been identified for all combinations, which were studied kinetically
(Table 2).
2g
19.35c
0.67c
2h
2i
19.36a
19.62a
0.67a
0.67a
(CH3)2C NO2
H2C NO2
2j
2k
2l
20.61b
20.71b
21.54b
0.69b
0.60b
0.62b
−
=
−
=
−
=
CH3CH NO2
Scheme 2 Reactions of the potassium salts of the carbanions 2a–l with
the 2-benzylidene-indan-1,3-diones 1a–d in DMSO.
a From ref. 5. b From ref. 17. c From ref. 18.
All Michael adducts 3− and 3 show characteristic H NMR
1
Results and discussion
spectra with Ha and Hb as doublets from d = 5.03–5.85 ppm
for Ha and d = 3.98–4.40 ppm for Hb. The double set of signals
for product 3al indicates that it exists as a pair of diastereomers
(2 : 1).
Preparation of the electrophiles 1a–d
The 2-benzylidene-indan-1,3-diones 1a–d were synthesized by
Knoevenagel condensation from indan-1,3-dione and substituted
benzaldehydes in the presence of catalytic amounts of piperidine
in boiling ethanol (Scheme 1) following the protocol of Behera
and Nayak.19
Kinetic investigations in DMSO
The kinetic investigations were performed at 20 ◦C in dimethyl
sulfoxide by using the stopped-flow technique. All reactions
reported in this paper proceeded quantitatively, and the second-
order rate constants k2 (Table 3) were determined photometrically
by monitoring the decrease of the absorbances of the colored
electrophiles 1a–d at their absorption maxima. The carbanions 2a–
l were either employed as potassium salts or were freshly generated
by deprotonation of the corresponding CH acids with 1.05 equiv-
alents of KOtBu. In general, the carbanions were applied in high
excess over the electrophiles (10 to 100 equivalents), giving rise to
almost constant carbanion concentrations (10−3 to 10−4 mol L−1)
during the kinetic measurements. As a consequence, exponential
decays of the concentrations of the colored electrophiles were
observed (eqn (2)). The first-order rate constants k1W were obtained
Scheme 1 Preparation of the 2-benzylidene-indan-1,3-diones via Kno-
evenagel condensation.
This journal is
The Royal Society of Chemistry 2007
Org. Biomol. Chem., 2007, 5, 3020–3026 | 3021
©

View Article Online
Table 3 Second-order rate constants k2 for the reactions of 2-benzyl-
idene-indan-1,3-diones 1a–d with stabilized carbanions 2a–l in DMSO at
the k1W versus [2]0 plots do not go through the origin. Because all
reactions proceed with quantitative formation of the adducts, we
can presently not explain this phenomenon. All second-order rate
constants k2 (L mol−1 s−1) for the Michael additions are listed in
Table 3.
20 ◦
C
Electrophile
Ea
C−
Base
k2/L mol−1 s−1
1ab
−14.68
2b
2c
2d
2e
2f
2h
2i
2j
2k
2l
2b
2c
2d
2e
2f
2h
2i
2j
2k
2b
2d
2f
2g
2h
2a
2b
2d
—
KOtBu
—
—
KOtBu
—
KOtBu
KOtBu
KOtBu
KOtBu
—
KOtBu
—
—
KOtBu
—
3.78 × 101
3.73 × 101
1.23 × 102
9.87 × 102
3.12 × 102
1.27 × 103
1.86 × 103
1.94 × 103
3.31 × 103
4.32 × 103
2.79 × 102
2.08 × 102
8.86 × 102
6.25 × 103
2.15 × 103
8.17 × 103
1.00 × 104
6.86 × 103
1.32 × 104
1.80 × 104
3.87 × 104
5.69 × 104
1.18 × 105
2.07 × 105
1.06 × 103
1.06 × 105
2.72 × 105
Correlation analysis
If eqn (1) holds for the reactions of the 2-benzylidene-indan-
1,3-diones 1a–d with the carbanions 2a–l, plots of (log k2)/s vs.
N should be linear with slopes of 1. Fig. 3 shows that this is
approximately the case.
1bb
−13.56
−11.32
—
KOtBu
KOtBu
—
1cb
1dc
—
KOtBu
KOtBu
—
—
—
−10.11
—
b
a Derived from eqn (1). kmax(DMSO) = 523 (1a), 493 (1b), 388 (1c) nm,
Fig. 3 Correlation of (log k2)/s with the corresponding nucleophilicity
parameters N of the carbanions 2a–l for the reactions of 2-benzylidene-in-
dan-1,3-diones 1a–d with carbanions 2a–l in DMSO at 20 ◦C. Open
symbols were not included for the calculation of the correlation lines.
from this work. c kmax(DMSO–H2O 50 : 50, v/v) = 343 nm, from ref. 20
by least-squares fitting of the time-dependent absorbances of the
electrophiles to At = A0exp (−k1W t) + C.
The correlation lines drawn in Fig. 3 result from a least-squares
fit of calculated and experimental rate constants (minimization of
D2 = R(log k2 − s(N + E))2 with the nonlinear solver What’s Best!
by Lindo Systems Inc.) using the second-order rate constants k2
given in Table 3 and the N and s parameters of 2a–l listed in Table 1.
Note that this procedure enforces slopes of 1 for plots of (log k2)/s
vs. N because eqn (1) does not include an electrophile-specific slope
parameter, in contrast to a more general equation, which we have
recently employed for SN2 reactions.21 The nitronate anions 2j and
2l deviate strongly from the correlations for the other nucleophiles
and have not been included in the minimization process. According
to eqn (1), the intercepts on the y-axis, which equal the negative
intercepts on the x-axis (because of the enforced unity slopes)
correspond to the electrophilicity parameters E.
–d[1]/dt = k1W [1]
(2)
Plots of k1W versus the nucleophile concentrations [2]0 give
straight lines with the slopes k2 as shown for one example in Fig. 2
and for all other kinetic experiments in the ESI.† In some cases,
While the correlations in Fig. 3 are only of moderate quality,
one can see that the relative electrophilicities of the 2-benzylidene-
indan-1,3-diones 1 are almost independent of the nature of the
carbanionic reaction partner. However, there seem to be some
regularities of the deviations of some of the carbanions. Thus,
the 2-nitropropyl anion 2j reacts approximately one order of
magnitude more slowly with 1a and 1b than expected from its
nucleophilicity parameters. Because 2j is the only trisubstituted
carbanion studied, this deviation may be a consequence of steric
effects due to the fact that the 2-benzylidene-1,3-indandiones 1 are
sterically more congested than the reference benzhydrylium ions.
On the other hand, the dimedone anion 2b is generally 2-times
more reactive than expected, and it cannot be due to a smaller
Fig. 2 Determination of the second-order rate constant k2 = 123 L
mol−1 s−1 for the reaction of 1a with the potassium salt of acetylacetone 2d
in DMSO at 20 ◦C.
3022 | Org. Biomol. Chem., 2007, 5, 3020–3026
This journal is
The Royal Society of Chemistry 2007
©

View Article Online
Fig. 4 Rate constants for the reactions of carbanions with the 2-benzylidene-indan-1,3-diones 1a–d and with reference electrophiles (quinone methides
and benzhydrylium ions) in DMSO at 20 ◦C. The rate constants for the reactions with 1a–d were not used for the construction of the regression lines.
steric demand of this carbanion, because the analogously shaped
anion of Meldrum’s acid 2a deviates slightly in the other direction.
An alternative illustration of this behavior is shown in Fig. 4.
When the rate constants of the reactions of the carbanions 2 with
electrophiles are plotted against the E parameters given in ref. 2e
and 5, all data points for the carbanions 2a, 2d, 2h, 2i, and 2l
follow good correlations, but in the case of the dimedone anion
2b, the data points for the reactions with the 2-benzylidene-1,3-
indandiones 1a–1d are located above the correlation line for the
reference electrophiles, which are depicted in the upper part of
Fig. 4.
According to Fig. 5, the electrophilicities of the 2-benzylidene-
indan-1,3-diones 1a–d cover a range of more than four orders
of magnitude. This electrophilicity range is located between
1h, the least reactive representative of our series of reference
benzhydrylium ions, and 1k, the most reactive representative of
Fig. 5 Comparison of the electrophilicity parameters E of 2-benzyl-
idene-indan-1,3-diones 1a–d with reference electrophiles 1h–k.
a series of di-tert-butyl substituted quinone methides that have
tuted 2-benzylidene-indan-1,3-diones 1b–d. This reactivity order
is surprising because indan-1,3-dione (pKa = 6.35–7.82 in DMSO–
H2O, v/v = 90 : 10 to 10 : 90)23 is much more acidic than
malononitrile (pKa(DMSO) = 11.1, pKa(H2O) = 11.2).24,25
been used as reference electrophiles.5
Donor substituents on the phenyl ring lower the electrophilicity,
+
and Fig. 6 shows a linear correlation with Hammett’s rp
constants.2e,22 For nucleophiles with s = 0.7, the slope corresponds
to a Hammett reaction constant of q = 1.6. A comparison with
the corresponding values for the structurally related benzyliden-
emalononitriles 1e–g (1e: X = NMe2; 1f: X = OMe, 1g: X = H)
indicates that the electrophilicities of these two types of Michael
acceptors are affected by the para substituents X in a similar way.
However, the benzylidenemalononitriles 1e–g are about 0.5
orders of magnitude more reactive than the analogously substi-
With the assumption that the stabilization of the carbanions
obtained by the addition of nucleophiles to 2-benzylidene-1,3-
indandiones 1a–d and benzylidenemalononitriles 1e–g corre-
sponds to these pKa values, one would expect that nucleophilic
additions to 1a–d have a higher thermodynamic driving force
than the nucleophilic additions to the analogously substituted
malononitriles 1e–g. If ground-state effects are neglected, the
higher reactivities of compounds 1e–g compared to analogously
This journal is
The Royal Society of Chemistry 2007
Org. Biomol. Chem., 2007, 5, 3020–3026 | 3023
©

View Article Online
Table 5 Second-order rate constants k2 for the reactions of piperidine
with reference benzhydryliums Ar2CH+ in DMSO, DMSO–H2O (50 :
50 v,v), and water at 20 ◦
C
k2/L mol−1 s−1
in DMSO–H2O
(50 : 50)c
Ar2CH+
Ea
in DMSOb
in H2Od
1h
1l
1m
1n
−10.04
−8.76
−8.22
−7.02
1.13 × 105
6.67 × 105
2.51 × 106
—
2.92 × 103
2.06 × 104
4.78 × 104
3.15 × 105
3.05 × 103
9.01 × 103
2.64 × 104
6.09 × 104
a From ref. 2e. b From ref. 4f. c This work (for details see the ESI†). d From
ref. 4a.
derived from the nucleophilicity parameters N and s of amines
in DMSO with Bernasconi’s experimental values in DMSO–H2O
(50 : 50 v,v).16 Entry 3 in Table 4 confirms this conclusion and
shows that the calculated rate constant for the addition of n-
propylamine to 1d agrees with the experimental rate constant for
the addition of n-butylamine to 1d in DMSO–H2O (50 : 50 v,v)
within a factor of 3.
On the other hand, the close similarity of the rates of the reac-
tions of 1d with amines in DMSO and DMSO–H2O (50 : 50 v,v)
is surprising because it is well-known that amine nucleophilicities
derived from reactions with benzhydrylium ions are considerably
lower in water than in DMSO (Table 5).
In line with previously reported rate constants for reactions
of amines with benzhydrylium ions in DMSO4f and water,4a we
have now found that piperidine reacts 32–52 times faster with
benzhydrylium ions 1h–n (Scheme 3) in DMSO than in DMSO–
H2O (50 : 50 v,v) as shown in Table 5.
Fig. 6 Correlation between the electrophilicity parameters E in DMSO
+
of the benzylidene-indan-1,3-diones 1a–d (circles; E = 2.34rp −9.78) and
+
the benzylidenemalononitriles 1e–g (squares; E = 2.30rp −9.28) with the
+
+
Hammett rp+-values for X. (rp Values were taken from ref. 22; rp for 1a
was taken from ref. 2e).
substituted 2-benzylidene-1,3-indandiones 1b–d must, therefore,
be due to lower intrinsic barriers for the additions to 1e–g. This
conclusion has previously been drawn by Bernasconi et al. from a
related series of experiments.20b,26
In order to examine the applicability of the electrophilicity
parameters E of the 2-benzylidene-indan-1,3-diones 1 for their
reactions with other types of nucleophiles, we have compared
experimental and calculated rate constants for the reactions of
1d with amines (Table 4).
Entries 1 and 2 in Table 4 indicate that the experimental
second-order rate constants k2,exp for the addition of piperidine
and morpholine to 2-benzylidene-indan-1,3-dione 1d in DMSO
are about three-times larger than the corresponding second-order
rate constants k2,calc calculated by eqn (1). This agreement is within
the previously postulated reliability of eqn (1).
Scheme 3 Benzhydrylium ions used for the comparison of the nucle-
Because the experimental second-order rate constants k2,exp in
DMSO are only about 1.5- to 2-times larger than the correspond-
ing k2,exp in DMSO–H2O (50 : 50 v,v, Table 4, right column),
we can also compare the calculated second-order rate constants
ophilicities of piperidine in different solvents.
Therefore the question arises whether the similar rate ofaddition
of piperidine and morpholine to the Michael acceptor 1d in DMSO
and DMSO–H2O (50 : 50 v,v) is caused by an increase of the
electrophilicity of 1d in the presence of water.
Table 4 Comparison of calculated and experimental second-order rate
constants (in L mol−1 s−1, DMSO, 20 ◦C) for the additions of amines to
2-benzylidene-indan-1,3-dione (1d)
In order to examine this question, we have compared the
rates of addition of the malononitrile anion 2h to 1a, 1b, and
the benzhydrylium ion 1h in DMSO and in aqueous solvents.
The carbanion 2h has been selected for this purpose because
its solvation has been reported to be of similar magnitude in
DMSO and water.5,27 Table 6 shows that the reaction of 2h with
1a and 1b is, indeed, 3–5 times faster in DMSO–H2O (50 : 50 v,v)
than in DMSO, whereas the reaction of this carbanion with the
benzhydrylium ion 1h is 12-times slower in water than in pure
DMSO.
Nucleophile
Piperidine
N/s a
k2,calc (eqn (1))
1.02 × 105
3.77 × 104
3.63 × 103
k2,exp
b
c
b
c
1
2
3
17.19/0.71
16.96/0.67
15.70/0.64
3.01 × 105
2.10 × 105
1.11 × 105
6.30 × 104
Morpholine
n-Propylamine
9.34 × 103c,d
a In DMSO, from ref. 4f. b In DMSO, this work. c In DMSO–H2O (50 :
50 v,v), from ref. 16. d The experimental value k2,exp refers to the reaction
of 1d with n-butylamine.
Thus, the presence of 50% water in DMSO appears to increase
the electrophilicities of the 2-benzylidene-1,3-indandiones 1a,b
3024 | Org. Biomol. Chem., 2007, 5, 3020–3026
This journal is
The Royal Society of Chemistry 2007
©

View Article Online
Table 6 Comparison of the second-order rate constants of the reactions
of malononitrile anion 2h with Michael acceptors 1a and 1b and the
Notes and references
benzhydrylium ion 1h in different solvents at 20 ◦
k2/L mol−1 s−1
C
1 (a) H. Mayr and A. R. Ofial, Pure Appl. Chem., 2005, 77, 1807–1821;
(b) H. Mayr and A. R. Ofial, in Carbocation Chemistry, ed. G. A. Olah
and G. K. S. Prakash, Wiley, Hoboken (N.J.), 2004, ch. 13, pp. 331–358;
(c) A. R. Ofial and H. Mayr, Macromol. Symp., 2004, 215, 353–367;
(d) H. Mayr, B. Kempf and A. R. Ofial, Acc. Chem. Res., 2003, 36,
66–77; (e) H. Mayr, O. Kuhn, M. F. Gotta and M. Patz, J. Phys. Org.
Chem., 1998, 11, 642–654; (f) H. Mayr, M. Patz, M. F. Gotta and
A. R. Ofial, Pure Appl. Chem., 1998, 70, 1993–2000; (g) H. Mayr and
M. Patz, Angew. Chem., 1994, 106, 990–1010, (Angew. Chem., Int. Ed.
Engl., 1994, 33, 938–957).
2 For reactions of carbocations with p-nucleophiles, see: (a) S. Lakhdar,
M. Westermaier, F. Terrier, R. Goumont, T. Boubaker, A. R. Ofial and
H. Mayr, J. Org. Chem., 2006, 71, 9088–9095; (b) A. D. Dilman and
H. Mayr, Eur. J. Org. Chem., 2005, 9, 1760–1764; (c) T. Tokuyasu and
H. Mayr, Eur. J. Org. Chem., 2004, 13, 2791–2796; (d) B. Kempf, N.
Hampel, A. R. Ofial and H. Mayr, Chem.–Eur. J., 2003, 9, 2209–2218;
(e) H. Mayr, M. F. Gotta, T. Bug, N. Hering, B. Irrgang, B. Janker, B.
Kempf, R. Loos, A. R. Ofial, G. Remennikov and H. Schimmel, J. Am.
Chem. Soc., 2001, 123, 9500–9512.
3 For reactions of carbocations with hydride donors, see: (a) H. Mayr,
G. Lang and A. R. Ofial, J. Am. Chem. Soc., 2002, 124, 4076–4083;
(b) M. A. Funke and H. Mayr, Chem.–Eur. J., 1997, 3, 1214–1222.
4 For reactions of carbocations with n-nucleophiles, see: (a) F. Brotzel,
Y. C. Chu and H. Mayr, J. Org. Chem., 2007, 72, 3679–3688; (b) F.
Brotzel, B. Kempf, T. Singer, H. Zipse and H. Mayr, Chem.–Eur. J.,
2007, 13, 336–345; (c) T. B. Phan and H. Mayr, Eur. J. Org. Chem.,
2006, 2530–2537; (d) B. Kempf and H. Mayr, Chem.–Eur. J., 2005, 11,
917–927; (e) T. B. Phan and H. Mayr, Can. J. Chem., 2005, 83, 1554–
1560; (f) S. Minegishi and H. Mayr, J. Am. Chem. Soc., 2003, 125,
286–295.
Electrophile in DMSO
in DMSO–H2O (50 : 50)
in H2O
1a
1.27 × 103
8.17 × 103
1.76 × 106, a
6.39 × 103
2.28 × 104
—
—
—
1b
(lil)2CH+
1.50 × 105, b
a From ref. 5. b From ref. 27.
(compared with benzhydrylium ion 1h as a reference) by approx-
imately one order of magnitude. The observed similar reactivities
of amines towards 1 in DMSO and DMSO–H2O (50 : 50 v,v)
can therefore be explained by a compensation effect, i.e., hy-
dration of amines reduces their nucleophilicities by a similar
amount as hydration increases the electrophilicities of the Michael
acceptors 1.
A more quantitative analysis of these data appears problematic,
because Bernasconi et al.16,28 and Lee et al.29 have previously
suggested that the transition states of the amine additions may
also be stabilized by O–H interactions as depicted in Scheme 4.
Because the additions of carbanions to 1a–d, which are described
in Table 3, cannot profit from such O–H interactions, the good
agreement between calculated and experimental rate constants
in Table 4 argues against a large contribution of these inter-
actions.
5 R. Lucius, R. Loos and H. Mayr, Angew. Chem., 2002, 114, 97–102,
(Angew. Chem., Int. Ed., 2002, 41, 91–95).
6 T. Lemek and H. Mayr, J. Org. Chem., 2003, 68, 6880–6886.
7 See references 10–13 cited in: D. B. Ramachary, K. Anebouselvy, N. S.
Chowdari and C. F. Barbas III, J. Org. Chem., 2004, 69, 5838–5849.
8 (a) R. Cammi, C. Ghio and J. Tomasi, Int. J. Quantum Chem., 1986, 29,
527–539; (b) E. Liedl and P. Wolschann, Monatsh. Chem., 1982, 113,
1067–1071; (c) H. Goerner, J. Leitich, O. E. Polansky, W. Riemer, U.
Ritter-Thomas and B. Schlamann, Monatsh. Chem., 1980, 111, 309–
329; (d) P. Margaretha, Tetrahedron, 1972, 28, 83–87; (e) P. Margaretha
and O. E. Polansky, Monatsh. Chem., 1969, 100, 576–583.
9 (a) J. Bloxham and C. P. Dell, J. Chem. Soc., Perkin Trans. 1, 1993, 24,
3055–3059; (b) N. F. Eweiss, J. Heterocycl. Chem., 1982, 19, 273–277;
(c) P. P. Righetti, A. Gamba, G. Tacconi and G. Desimoni, Tetrahedron,
1981, 37, 1779–1785; (d) J. Bitter, J. Leitich, H. Partale, O. E. Polansky,
W. Riemer, U. Ritter-Thomas, B. Schlamann and B. Stilkerieg, Chem.
Ber., 1980, 113, 1020–1032.
Scheme 4 Addition of an amine to 2-benzylidene-1,3-indandione 1 (TS:
transition state, T*: zwitterionic intermediate).
Conclusions
10 L. P. Zalukaevs and I. Anokhina, J. Gen. Chem. USSR, 1964, 34, 834–
836, (Zh. Obshch. Khim., 1964, 34, 840–843).
The 2-benzylidene-indan-1,3-diones 1a–d have been shown to have
electrophilicity parameters in the range of −10 > E > −15. With
these data and the previously published nucleophilicity parameters
of carbanions and amines,30 it has become possible to calculate
the rates of additions of these nucleophiles to 2-benzylidene-
indan-1,3-diones 1a–d with an accuracy of better than a factor
of 3 in dimethyl sulfoxide solution. Because hydration appears to
increase the electrophilicities of 1a–d much more than it affects
the electrophilicities of the previously used reference electrophiles
(benzhydrylium ions and quinone methides), we recommend using
the E parameters of 2-benzylidene-1-3-indandiones 1a–d reported
in this work only for predictions of rate constants in aprotic
solvents.
11 T. Zimaity, E.-S. Afsah and M. Hammouda, Indian J. Chem., Sect. B:
Org. Chem. Incl. Med. Chem., 1979, 17, 578–580.
12 L. P. Zalukaevs and D. G. Vnenkovskaya, Zh. Org. Khim., 1966, 2,
672–674.
13 E. I. Stankevich and G. Y. Yanags, J. Gen. Chem. USSR, 1962, 32,
1123–1126, (Zh. Obshch. Khim., 1962, 32, 1146–1151).
14 (a) B. A. Arbuzov, T. D. Sorokina, N. P. Bogonostseva and V. S.
Vinogradova, Dokl. Akad. Nauk SSSR, 1966, 171, 605–608; (b) A.
Mustafa, M. M. Sidky and F. M. Soliman, Tetrahedron, 1967, 23, 99–
105; (c) F. M. Soliman, M. M. Said and S. S. Maigali, Heteroat. Chem.,
1997, 8, 157–164.
15 X.-Q. Zhu, H.-Y. Wang, J.-S. Wang and Y.-C. Liu, J. Org. Chem., 2001,
66, 344–347.
16 C. F. Bernasconi and M. W. Stronach, J. Am. Chem. Soc., 1991, 113,
2222–2227.
17 T. Bug, T. Lemek and H. Mayr, J. Org. Chem., 2004, 69, 7565–7576.
18 S. T. A. Berger, A. R. Ofial and H. Mayr, J. Am. Chem. Soc., 2007, 129,
9753–9761.
19 R. K. Behera and A. Nayak, Indian J. Chem. B, 1976, 14, 223–224.
20 (a) C. F. Bernasconi, A. Laibelman and J. L. Zitomer, J. Am. Chem.
Soc., 1985, 107, 6563–6570; (b) C. F. Bernasconi, A. Laibelman and
J. L. Zitomer, J. Am. Chem. Soc., 1985, 107, 6570–6575.
21 T. B. Phan, M. Breugst and H. Mayr, Angew. Chem., 2006, 118, 3954–
3959, (Angew. Chem., Int. Ed., 2006, 45, 3869–3874).
Acknowledgements
Financial support by the Deutsche Forschungsgemeinschaft
(Ma 673–17) and the Fonds der Chemischen Industrie is gratefully
acknowledged.
This journal is
The Royal Society of Chemistry 2007
Org. Biomol. Chem., 2007, 5, 3020–3026 | 3025
©

View Article Online
22 C. Hansch, A. Leo and R. W. Taft, Chem. Rev., 1991, 91, 165–
26 C. F. Bernasconi and R. B. Killion, Jr., J. Org. Chem., 1989, 54, 2878–
2885.
195.
23 C. F. Bernasconi and P. Paschalis, J. Am. Chem. Soc., 1986, 108, 2969–
27 T. Bug and H. Mayr, J. Am. Chem. Soc., 2003, 125, 12980–12986.
28 (a) C. F. Bernasconi, Acc. Chem. Res., 1987, 20, 301–308; (b) C. F.
Bernasconi, Tetrahedron, 1989, 45, 4017–4090.
29 H. K. Oh, J. H. Yang, H. W. Lee and I. Lee, J. Org. Chem., 2000, 65,
5391–5395.
2977.
24 F. G. Bordwell, J. A. Harrelson, Jr. and A. V. Satish, J. Org. Chem.,
1989, 54, 3101–3105.
25 A. Albert and E. P. Serjeant, The Determination of Ionization Constants:
A Laboratory Manual, Chapman and Hall, London, 3rd edn, 1984,
pp. 137–160.
30 For a database of reactivity parameters E, N, and s, see: http://
www.cup.uni-muenchen.de/oc/mayr/DBintro.html.
3026 | Org. Biomol. Chem., 2007, 5, 3020–3026
This journal is
The Royal Society of Chemistry 2007
©