Using phenyl cations as probes for establishing electrophilicity - Nucleophilicity relations

Article abstract of DOI:10.1021/jo7019509

(Chemical Equation Presented) N,N-Dimethyl-4-aminophenyl cation is used as an electrophilic probe for determining the relative reactivity of nucleophiles. The singlet state (¹1) of this cation is completely unselective (reaction rates with benzene, MeCN, and trifluoroethanol within a factor of 5). The corresponding triplet (³1) does not react with alcohols and MeCN. The rates of reaction of the latter intermediate with 23 π, σ, and n nucleophiles are measured by competition experiments and found to vary over only 2 orders of magnitude over a range of 22 units of the nucleophilicity parameter N introduced by Mayr. As far as one can judge with the considerable scatter of the data, fitting the data of both amines and π nucleophiles is possible only by using a modified Mayr's equation: log k = s(E + eN) with e = 0.33. The reduced dependence on N is explained by the fact that in the case of diradicalic triplet ³1 interaction with the nucleophile involves a half-filled (σ) orbital, which is empty in singlet ¹1. It is suggested that Mayr's equation can be extended to quite diverse reactions, but a scaling factor of e < 1 may have to be introduced in some cases, according to the electronic structure of the electrophilic probe used.

Full text of DOI:10.1021/jo7019509

Using Phenyl Cations as Probes for Establishing
Electrophilicity-Nucleophilicity Relations
Valentina Dichiarante, Maurizio Fagnoni, and Angelo Albini*
Department of Organic Chemistry, UniVersity of PaVia, Via Taramelli 10, 27100 PaVia, Italy
angelo.albini@unipV.it
ReceiVed September 5, 2007
N,N-Dimethyl-4-aminophenyl cation is used as an electrophilic probe for determining the relative reactivity
of nucleophiles. The singlet state (11) of this cation is completely unselective (reaction rates with benzene,
MeCN, and trifluoroethanol within a factor of 5). The corresponding triplet (31) does not react with
alcohols and MeCN. The rates of reaction of the latter intermediate with 23 π, σ, and n nucleophiles are
measured by competition experiments and found to vary over only 2 orders of magnitude over a range
of 22 units of the nucleophilicity parameter N introduced by Mayr. As far as one can judge with the
considerable scatter of the data, fitting the data of both amines and π nucleophiles is possible only by
using a modified Mayr’s equation: log k ) s(E + eN) with e ) 0.33. The reduced dependence on N is
explained by the fact that in the case of diradicalic triplet 31 interaction with the nucleophile involves a
half-filled (σ) orbital, which is empty in singlet 11. It is suggested that Mayr’s equation can be extended
to quite diverse reactions, but a scaling factor of e < 1 may have to be introduced in some cases, according
to the electronic structure of the electrophilic probe used.
Introduction
This equation, as well as a more general one proposed by
Edwards,1f has been used for a variety of reactions and has
contributed to distinguishing SN1 and SN2 reactions when
applied to solvolysis. Experimental attempts to develop a
universal kinetic scale of nucleophilicity have been reported by
several groups over the last 50 years. From this point of view,
a convenient model is the reaction of a cation with an anion to
form a covalent molecule, since this is an elementary step
occurring in more complex reactions, e.g., SN1 processes. In
this case, the nucleophile attacks a positive center, without the
necessity of displacing any leaving group, and one need not
worry about a change in mechanism along a series of nucleo-
philes. Following this reasoning, Ritchie found the rate of
reaction of various cations (trityl, aryldiazonium, and tropylium
ions) with nucleophiles could be characterized by a single,
electrophile-independent parameter and established a nucleo-
philicity scale.1d More recently, Mayr persuasively argued in
favor of universal electrophilic/nucleophilic scales.2 His work
was based on the use of benzhydryl cations (diarylmethylium
ions) as model electrophiles (see Scheme 1).2a-d
Most organic reactions can be envisioned as the combination
of an electrophile with a nucleophile. Therefore, it is useful to
have available experimental scales of electrophilicity and
nucleophilicity, in order to rationalize the reaction occurring
and to predict whether a given reaction will take place.1 The
first attempt at a quantitative treatment of the reactivity of
nucleophiles has been carried out by Swain and Scott for SN2
reactions and resulted in eq 1,1b where s and nx are empirical
parameters of the electrophile and, respectively, of the nucleo-
phile.
log kx/kH O ) snx
(1)
2
* Address correspondence to this author. Fax: +39-0382-987323.
(1) (a) Phan, T. B.; Breugst, M.; Mayr, H. Angew. Chem., Int. Ed. 2006,
45, 3869. (b) Swain, C. G.; Scott, C. B. J. Am. Chem. Soc. 1953, 75, 141.
(c) Nucleophilicity; Harris, M., McManus, S. P., Eds.; Adv. Chem. Ser.
No. 215; American Chemical Society: Washington, DC, 1987. (d) Richtie,
C. D. Acc. Chem. Res. 1972, 5, 348. (e) Kane-Maguire, L. A. P.; Honig, E.
D.; Sweigart, D. A. Chem. ReV. 1984, 84, 525. (f) Edwards, J. O. J. Am.
Chem. Soc. 1956, 78, 1819. (g) Pearson, R. G. J. Org. Chem. 1987, 52,
2131. (h) Campodonico, P. R.; Aizman, A.; Contreras, R. J. Phys. Org.
Chem. 2004, 17, 273.
The second-order rate constants (k) for the reaction between
such cations and a variety of nucleophiles of different nature,
10.1021/jo7019509 CCC: $40.75 © 2008 American Chemical Society
Published on Web 01/18/2008
1282
J. Org. Chem. 2008, 73, 1282-1289

Establishing Electrophilicity-Nucleophilicity Relations
SCHEME 1. Reaction of Benzhydryl Cation with π-, σ-,
and n-Nucleophiles
CHART 1. Charged and Neutral Electrophiles Tested
Besides Benzhydryl Cations
such as π- (alkenes, arenes, enolates), σ- (hydrides), and n- (N-,
O-, P-centered) nucleophiles were measured and a logarithmic
scale of the relative reactivity (parameter N) was established
by taking 2-methyl-1-pentene as the reference, resulting in a
range from N ) -4.47 to 22.62. Likewise, comparing different
cations the (nucleophile-independent) electrophilicity parameter
E was determined, with a range from -10.04 of a 4,4′-diamino
derivative to 6.02 of the 4,4′-dichloro derivative, with E ) 0
for the 4,4′-dimethoxybenzhydryl cation.2e The rate constant for
a given reaction was linearly related to such parameters,
although the slope was somewhat nucleophile-dependent and a
further parameter s (typically 0.6 to 1 for n-nucleophiles, 1 to
1.5 for π-nucleophiles) was introduced, see eq 2.
CHART 2
log k(20 °C) ) s(E + N)
(2)
Benzhydryl cations were convenient probes because the strong
absorption in the visible made their reaction easy to monitor
and because they were practically generated under mild condi-
tions. Furthermore, the electrophilicity could be conveniently
tuned by introducing electron-donating or -accepting ring
substituents.2a-d Having available the above set of parameters,
the rate k could be predicted over a range of >40 orders of
magnitude by means of eq 2. Most measurements were carried
in MeCN, which is too weak a nucleophile for reacting with
these delocalized carbocations.
high reactivity of these species have led some authors to doubt
that these can be defined as intermediates.3
A significant step would be extension to divalent carbocations,4a
such as phenyl cations. These high-energy intermediates have
different characteristics with respect to previously considered
intermediates. A look to Chart 1 shows in fact that both neutral
and charged electrophiles tested in the work presented above
shared a common characteristic, namely a delocalized π orbital
as the LUMO. Differently from these (see as an example a
benzyl cation in Chart 2, a), phenyl cations are not π cations.
More precisely, phenyl cations exist in two spin states. The
electronic configuration of the singlet is well described as π6σ0,
and this is a localized carbocation, comparable to singlet
carbenes or to a trivalent alkyl carbocation (see Chart 2, b),
except for the sp2 hybridization of the vacant orbital and the
fact that C1 is part of the aromatic system. On the contrary the
triplet has a π5σ1 structure, similarly to triplet carbenes (see
Chart 2, c).
Phenyl cations are virtually inaccessible by thermal reactions4b
but are smoothly photochemically generated5a and have been
demonstrated to be versatile electrophiles in synthesis.5b The
fact that they do not enjoy the stabilization arising from
delocalization characteristic of π cations suggests that these
species may be a middle point between the poor selectivity of
sp3 alkyl carbocations and the high selectivity of benzhydryl
cations. Similarly to carbenes, but differently from (necessarily
singlet) benzhydryl cations, these have accessible singlet and
triplet states of different structure and chemistry (in turn
susceptible to tuning by substituents), further enriching the
Equation 2 has been successfully applied to nucleophiles of
various nature (see Scheme 1), while maintaining a single set
of parameters. The question is then, how general is this scale,
e.g., when changing the electrophilic probe. Thus, further studies
have shown that eq 2 applies to the reaction of the same
nucleophiles with complexed allyl cations, iminium cations, and
dithiocarbenium ions,2f as well as with some neutral electro-
philes,includingMichaelacceptorssuchasbenzylidenemalonitriles2g
and metal-complexed and electron-withdrawing substituted
aromatics (trinitrobenzene and heterocyclic analogues, see Chart
1).2h However, Mayr recently reported that the application of
eq 2 to reactions of sulfonium salts or of alkyl halides proceeding
via an SN2 mechanism required some adjustment,1a as will be
discussed below.
One may wonder whether the remarkably large span of
reagents can be further extended. As an example, the simplest
carbocations are alkyl carbocations. For the tert-butyl cation,
the very high E 8.5-9 value has been estimated,2i although the
(2) (a) Mayr, H.; Patz, M. Angew. Chem., Int. Ed. 1994, 33, 938. (b)
Mayr, H.; Ofial, A. R. Pure Appl. Chem. 2005, 77, 1807. (c) Mayr, H.;
Kempf, B.; Ofial, A. R. Acc. Chem. Res. 2003, 36, 66. (d) Mayr, H.; Mu¨ller,
K. H.; Ofial, A. R.; Bu¨hl, M. H. J. Am. Chem. Soc. 1999, 121, 2418. (e)
Mayr, H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.; Janker, B.; Kempf,
B.; Loos, R.; Ofial, A. R.; Remennikov, G.; Schimmel, H. J. Am. Chem.
Soc. 2001, 123, 9500. (f) Arend, M.; Westermann, B.; Risch, N. Angew.
Chem. 1998, 110, 1096; Angew. Chem., Int. Ed. 1998, 37, 1045. (g) Lemek,
T.; Mayr, H. J. Org. Chem. 2003, 68, 6880. (h) Terrier, F.; Lakhdar, S.;
Boubacker, T.; Goumont, R. J. Org. Chem. 2005, 70, 6242. (i) Roth, M.;
Mayr, H. Angew. Chem., Int. Ed. 1995, 34, 2250.
(3) (a) Isaacs, N. Physical Organic Chemistry; Longman Scientific &
Technical: Burnt Mill, NY, 1995. (b) Toteva, M. M.; Richard, J. P. J. Am.
Chem. Soc. 1996, 118, 11434. (c) Zheng, L. X.; Thibblin, A. J. Chem. Soc.,
Perkin Trans. 2, 2001, 1600.
(4) (a) DiValent Carbocations; Stang, P. J., Rappoport, Z., Eds.; Wiley:
Chichester, UK, 1997. (b) Stang, P. J. in ref 4a, p 451.
(5) (a) Freccero, M.; Fagnoni, M.; Albini, A. J. Am. Chem. Soc. 2003,
125, 13182. (b) Fagnoni, M.; Albini, A. Acc. Chem. Res. 2005, 38, 713.
J. Org. Chem, Vol. 73, No. 4, 2008 1283

Dichiarante et al.
SCHEME 2. Products from the Irradiation of N,N-Dimethyl-4-aminophenyldiazonium Tetrafluoroborate (2) and from
N,N-Dimethyl-4-chloroaniline (3)
palette.6 Importantly, at least some of these cations can be
selectively generated either in the singlet or in the triplet state
through the appropriate choice of the conditions. We reasoned
that using phenyl cations as electrophilic probes may attain a
twofold target. First, this should offer a test for the generality
of eq 2. If these highly reactive electrophiles, in which the
LUMO has a different character, were amenable to the same
treatment and an E parameter could be assigned, the generality
of the approach would be strengthened. Second, a kinetic study
may improve the understanding of these as yet only partially
characterized intermediates.6d
Reactions of the Singlet Cation. Irradiation of diazonium
salt (2) in MeCN gave 4-N,N-dimethylaminoacetanilide (4), the
product from the Ritter addition of the cation to the solvent.
Likewise, in trifluoroethanol (TFE) ether 4′ was obtained. The
two solvents were compared by irradiating 2 in various mixtures
of these solvents, showing that the ether was formed in a
proportion somewhat lower than the solvents molar ratio.
π-Nucleophiles were arylated too, provided that they were used
at a sufficiently high concentration. Thus, with benzene (g1
M) in MeCN 4-N,N-dimethylaminobiphenyl (5) was formed
along with 4 in a higher proportion than the molar ratio between
PhH and MeCN (see Scheme 2). The results in mixed solvents
were plotted in Figure 1 as the ratio 4′/4 or 5/4 vs the NuH/
MeCN ratio, where NuH is the other component. In the limits
explored (up to 6 M benzene and to 4 M TFE) the data were
roughly fitted by a straight line passing for the origin, as is
expected for two traps (eqs 5 and 6) competing for the same
Results
In view of the above, we report here the reactivity with π-,
σ-, and n-nucleophiles of a phenyl cation, 4-N,N-dimethylami-
nophenyl cation (1). As previously demonstrated through
sensitization experiments, this intermediate could be generated
either in the singlet state, by direct photolysis of the corre-
sponding phenyldiazonium tetrafluoroborate (2) (see eq 3),7 or
in the triplet state, by photolysis of the corresponding phenyl
chloride (3) (see eq 4).
1
intermediate 1, photochemically formed from 2, see eq 7.
11 + MeCN f Me2NC6H4NHAc (1kMeCN
11 + NuH f Me2NC6H4Nu (1kNuH
)
(5)
(6)
)
Me2NC6H4N2+ (2) + hν f 1Me2NC6H4+ (11)
Me2NC6H4Cl (3) + hν f 3Me2NC6H4+ (31)
(3)
(4)
[4′]/[4] or [5]/[4] ) 1kNuH[NuH]/1kMeCN[MeCN] (7)
1
The slope from the plot gave the rate ratio kNuH/1kMeCN
,
respectively 0.8 for TFE and 4.0 for benzene. Allyltrimethyl-
silane seemed to give practically the same trapping ratio as
benzene, at least as far as was possible to measure, due to the
lower miscibility of this alkene with MeCN. It appeared thus
To compare the reactivity, irradiations up to moderate (<25%)
conversion were carried out.
(6) (a) Laali, K. K.; Rasul, G.; Prakash, G. K. S.; Olah, G. A. J. Org.
Chem. 2002, 67, 2913. (b) Filippi, A.; Lilla, G.; Occhiucci, G.; Sparapani,
C.; Ursini, O.; Speranza, M. J. Org. Chem. 1995, 60, 1250. (c) Aschi, M.;
Harvey, J. N. J. Chem. Soc., Perkin Trans. 2 1999, 1059. (d) Guizzardi,
B.; Mella, M.; Fagnoni, M.; Freccero, M.; Albini, A. J. Org. Chem. 2001,
66, 6353. (e) the chemical reactions of phenyl cation 1 have been exploited
i.a. for characterizing ionic liquids: Dichiarante, V.; Betti, C.; Fagnoni,
M.; Maia, A.; Landini, D.; Albini, A. Chem. Eur. J. 2007, 13, 1834. (f)
Previous flash photolysis work had shown that in the case of 3 in MeCN
only subsequent intermediates involved in the reduction of the triplet cation
31 had been detected, ref 6d.
1
+
that cation Me2NC6H4 (11) produced under these conditions
reacted unselectively with solvent and trap even when large
amounts of the latter were used and the study of this species
was not further pursued.
Reactions via the Triplet Cation. On the other hand, anilide
4 was not formed in a detectable amount upon photolysis of
N,N-dimethyl-4-chloroaniline (3) in MeCN, nor was ether 4′ in
TFE. Under these conditions, the products were aniline 6 and
diaminobiphenyl 7 resulting from the arylation of the starting
material (Scheme 2).6d On the other hand, in the presence of 1
(7) Milanesi, S.; Fagnoni, M.; Albini, A. Chem. Commun. 2003, 216.
Milanesi, S.; Fagnoni, M.; Albini, A. J. Org. Chem. 2005, 70, 603.
1284 J. Org. Chem., Vol. 73, No. 4, 2008

Establishing Electrophilicity-Nucleophilicity Relations
FIGURE 1. Plot of the photoproduct ratios ([) [4′]/[4] and (9) [5]/[4]
vs the molar ratio NuH (TFE or benzene)/MeCN in the mixed solvent.
FIGURE 2. Double reciprocal plot (part of the experimental points
shown) of iodoaniline formed vs iodide concentration in the presence
of benzene (9), 2,3-dimethyl-2-butene (O), triethylsilane (4), pyrro-
lidine (]), and pyrrole (0).
TABLE 1. Product from the Photolysis of Compound 3 (0.05 M)
in Acetonitrilea
additive
products (% yield)
none
C6H6, 1 M
Me2CdCMe2, 1 M
Et3SiH, 1 M
pyrrolidine, 1 M
NaI, 0.05 M
6 (57), 7 (36)
5 (48), 6 (21), 7 (11)
6 (14), 8 (70)
6 (95)
6 (33), 9 (43)
6 (5), 10 (85)
the presence of variable amounts of iodide (5 × 10-3 to 0.2
M). Reaction with the two traps, NuH and I- (eqs 8 and 9),
competed.
31 + NuH f Me2NC6H4Nu (3kNuH
31 + I- f Me NC H I (3k -)
)
(8)
(9)
a At 20-25% conversion.
2
6
4
I
M benzene in MeCN, biphenyl 5 became by far the main
product (60%), competing only with the starting aniline that
gave some 7. The ratio 5/4 was g100 from 3 (based on the
limit of detection of 4) in contrast to 0.17 with the diazonium
salt (similar results in TFE). Considering that MeCN and TFE
were ca. 19 and 13.5 M, this indicated that benzene trapped
triplet cation 3Me2NC6H4+ (31), produced under these conditions,
at a rate >1 × 103 to 2 × 103 times larger than either of these
solvents. This encouraged us to explore further traps (1 M),
again in experiments at <25% conversion in MeCN. As it
appears from Table 1, a further π-nucleophile such as 2,3-
dimethylbutene gave the arylated alkene 8, a σ-nucleophile such
as triethylsilane caused a clean reduction to 6, and a n-
nucleophile such as pyrrolidine gave a mixture of reduced 6
and phenylendiamine 9, in every case with no contamina-
tion by 4. Likewise, in the presence of sodium iodide, iodoa-
niline 10 was obtained in a good yield (see Scheme 2 and
Table 1).
As mentioned, the solvent did not interfere and in the
concentration range used, trapping according to eqs 8 and 9
predominated, minimizing other paths (such as reaction with
ground state 3 to give 7), and the iodide concentration was
low enough as to disregard the salt effect. Therefore, the iodide
and the nucleophile compete for the triplet cation, formed
with efficiency η. The rate of formation of the iodoaniline 10
3
-
-
is given by the ratio between trapping by iodide ( kI [I ]) and
3
-
the overall reaction (3kNuH[NuH] + kI [I ]). This compound is
formed at a rate expressed by eq 10 or, in the reverse form,
eq 10′ predicting a linear dependence in the double reciprocal
plot.
-
[ArI] ) η (3k -[I-])/(3k [NuH] + 3k -[I-])
(10)
I
NuH
I
[ArI]-1 ) η-1(1 + 3kNuH[NuH]/ 3k -[I-])
(10′)
I
The positive results with such different types of nucleophiles
encouraged us to explore the reaction and to measure the
competition between such traps. Indeed, it was found that similar
reactions took place with further π nucleophiles, including
alkenes, an alkyne, aromatics, and heterocycles (11-28), as well
as with further amines (30-33, see below).
Experiments with at least four I- concentrations were carried
out for each nucleophile. In accord with prediction, these gave
linear fittings with constant intercept ((12%, representative
examples are reported in Figure 2). The respective slope/
intercept ratios are reported in Table 2 and, being [NuH]
Competition Experiments. As hinted above, previous work
supports that these reactions proceeded via the intermediacy of
triplet phenyl cation 31.5a Trapping was effective at lower
concentrations than in the case of singlet cation and the reactivity
with the various nucleophiles could be explored under more
uniform characteristics, in particular in MeCN. A direct measure
3
known, correspond to the rate constants ratios 3kNuH/ kI . These
-
3
values allow a comparison of the reactivity of cation 1 with
nucleophiles and a test of the application of eq 2 (see the
Discussion).
Further parameters for evaluating the electrophilicity of
cations were based upon calculated thermodynamic quantities.
As an example, Houk and Mayr8 compared the empirical E
factor for benzhydryl cations with the calculated (B3LYP)
3
of the rate kNuH by flash photolysis was precluded, however,
because the cation had no convenient absorption.6f We thus
determined the relative rates through competition experiments.
Since iodide was a quite effective trap, the experiments were
carried out on 1 or 0.5 M solutions of the above traps (NuH) in
(8) Schindele, C.; Houk, K. N.; Mayr, H. J. Am. Chem. Soc. 2002, 124,
11208.
J. Org. Chem, Vol. 73, No. 4, 2008 1285

Dichiarante et al.
TABLE 2. Rate of Reaction of Triplet 4-N,N-Dimethylaminophenyl Cation with Nucleophiles
nucleophiles
N
s
slope/intercept
log 3kNuH
log 3kNuH/s
aromatics
11, fluorobenzene
12, chlorobenzene
13, benzene
14, 1,3-dimethoxybenzene
15, mesitylene
16, aniline
-5.60a
-7.00a
-6.29c
2.48d
-2.00b
12.64f
5.60a
1.20b
1.20b
1.20c
1.09d
1.30b
0.68f
1.10b
0.007
0.008
0.013
0.015
0.021
0.101
0.481
7.96
8.02
8.23
8.29
8.44
9.12
9.80
6.64
6.68
6.86
7.60e
6.49
13.41
8.91
17, N,N-dimethylaniline
heteroaromatics
1.10g
18, thiophene
19, Furan
20, pyrrole
-1.01g
1.36d
4.63h
0.011
0.019
0.303
8.16
8.40
9.60
7.42
6.41e
9.60
1.31d
1.00h
alkenes, alkynes
0.70c
21, 1-hexyne
22, 1-hexene
-2.19c
-2.25d
-1.00g
0.65d
0.012
0.020
0.022
0.035
0.040
0.052
0.058
0.107
8.20
8.42
8.46
8.66
8.72
8.83
8.88
9.15
11.71
8.50
6.04
7.40
8.72
9.40
9.87
9.15
0.99d
23, 2,3-dimethyl-2-butene
24, 2-methyl-2-butene
25, 2-methyl-1-pentene
26, allyltrimethylsilane
27, 2,3-dihydrofuran
28, 2,5-dimethyl-2,4-hexadiene
1.40g
1.17d
0.96d
1.00d
1.79d
0.94d
4.37i
0.90i
3.00b
1.00b
hydride
0.65d
29, triethylsilane
3.64d
0.036
8.67
13.34e
amines
0.67j
30, pyridine
12.90j
15.70k
15.97b
15.97l
0.006
0.009
0.057
0.135
7.90
8.09
8.87
9.24
11.78
12.63
14.79
14.92
31, n-propylamine
32, diethylamine
33, pyrrolidine
0.64k
0.60b
0.62l
a From ref 9a. b Parameters estimated from literature values for related compounds. c From ref 2a. d From ref 2e. e Values not used for the plot in Figure
4. f From ref 9b. g From ref 2c. h From ref 9c. i From ref 9d. j From ref 9e, value in CH2Cl2. k From ref 9f. l From ref 1a.
affinities of the same ions with methyl anion (∆Eo) and found
a linear relation (eq 11).
not related to reactivities, less so because calculations in vacuo
are considered, the qualitative indication is clearly for an
electrophilicity parameter E around 30, much above the limit
reached by benzhydryl cations (E ≈ 6). On this basis, both states
of cation 1 were expected to react at the diffusion-controlled
rate (k reaching the diffusion limit, k = 1.2 × 1010 M-1 s-1
since E + N . 10) even with weak nucleophiles (e.g., benzene,
N ) -6.29, acetonitrile)10a with no selectivity.
The experiments showed that this is indeed the case for singlet
11 that was formed by photolysis of the diazonium salt 2, eq 3,
with benzene (and alkenes) reacting only 4-5 times as much
as MeCN. It appears reasonable that the reaction rate with
E ) -0.3496∆Eo - 75.11
(11)
Following this approach, the affinities of cations 1,31 with
-
CH3 were calculated at the B3LYP-6-31g(d,p) level and the
E factor evaluated by using eq 11. This gave E ) 27.7 for the
triplet and E ) 30.9 for the singlet state of this ion.
Discussion
Singlet vs Triplet Phenyl Cation. The comparison between
phenyl cations 1,31 and alkyl cations on one hand and benzhydryl
cations on the other one is instructive under different aspects.
The singlet phenyl cation shows the universal reactivity typical
of alkyl cations. Paradigmatic is the trapping of both such ions
by a weak nucleophile such as MeCN forming an iminium
cation and, via water addition, an acetanilide (Ritter reaction).
Triplet phenyl cation and benzhydryl cations, on the other hand,
exhibit essentially the same chemistry, with formation of a C-C
bond with π-nucleophiles, of a C-N bond with amines
(accompanied by reduction with the phenyl cation) and hydride
transfer from a σ-nucleophile such as triethylsilane. Neither of
these cations react with MeCN; however, the two intermediates
differ in the reaction with alcohols, since Ph2CH+ give ethers
with both MeOH and TFE, while 31 does not (in TFE cation 31
is trapped by the π-nucleophile present, chloroaniline 3, despite
the relatively low concentration, 0.05 M, to give biphenylamine
7; in MeOH an electron-transfer path leads to reduction).
The calculated affinity of both singlet and triplet 1 for the
methyl anion is large. Although thermodynamic stabilities are
(9) (a) Gotta, M. F.; Mayr, H. J. Org. Chem. 1998, 63, 9769. (b) Brotzel,
F.; Chu, Y. C.; Mayr, H. J. Org. Chem. 2007, 72, 3679. (c) Kempf, B.;
Hampel, N.; Ofial, A. R.; Mayr, H. Chem. Eur. J. 2003, 9, 2209. (d) Dilman,
A. D.; Mayr, H. Eur. J. Org. Chem. 2005, 1760. (e) Brotzel, F.; Kempf,
B.; Singer, T.; Zipse, H.; Mayr, H. Chem. Eur. J. 2007, 13, 336. (f)
Minegishi, S. R.; Mayr, H. J. Am. Chem. Soc. 2003, 125, 286. (g) See also
the following site: http://cicum92.cup.uni-muenchen.de/mayr/reaktions-
datenbank/.
(10) (a) The addition of benzhydryl cations to acetonitrile has been
detected by flash photolysis [rate for the process Ph2CH+ + MeCN f Ph2-
CHNdC+Me is 1.1 × 105 M-1 s-1] but is reversible and does not contribute
to the products formed; see: Bartl, J.; Steenken, S.; Mayr, H.; McClelland,
R. A. J. Am. Chem Soc. 1990, 111, 6918. Therefore, this has no effect on
competitive trapping under steady state conditions and accordingly no N
parameter has been assigned. If referred to the irreversible reaction, N must
be largely negative and in the present discussion it has been assumed that
it is at least two units below that of benzene, the reaction of which is not
affected by MeCN. (b) The singlet phenyl cation is the intermediate also
in the thermal decomposition of phenyldiazonium salts. However, just as
in the case of alkyl cations it is doubtful whether the excessive reactivity
of this species allows it to be considered an intermediate in thermal reactions;
see: Glaser, R.; Horan, C. J.; Lewis, M.; Zollinger, H. J. Org. Chem. 1999,
64, 902.
1286 J. Org. Chem., Vol. 73, No. 4, 2008

Establishing Electrophilicity-Nucleophilicity Relations
FIGURE 3. Rate of reaction of triplet 4-N,N-dimethylaminophenyl
3
cation 1 with π-nucleophiles, viz. (4) aromatics, (]) heterocycles,
(0) alkenes, including 1-hexyne and 2,3-dihydrofuran, (/) a σ-nucleo-
phile (Et3SiH), and (×) n-nucleophiles (amines) (numbering, see Table
2) vs Mayr’s N parameters. Included are also the maximal rate values
(+) for the case of MeCN (assumed N ≈ -8,10a may be more negative)
and TFE (N ) 1.23), deduced from the nonreactivity in neat solvents
(3kMeCN,TFE e 1 × 105 M-1 s-1) as well as (b) for the reaction of the
FIGURE 4. Dependence of (log 3kNuH)/s vs N for the reactions (a, [)
of 31 with the nucleophiles in Table 2 (except 21 and 29). Also reported
literature data for the reactions of two benzhydryl cations, viz. (b, 2)
(4-ClC6H4)2CH+ 2a,e and (c, 9) (4-Me2NC6H4)2CH+ 2e as well as of
(d, b) S-methyldibenzothiophenium1a with various nucleophiles.
The broken line (e) corresponds to the equation (log 3kNuH)/s ) 8.11 +
N.
1
singlet ion 1 with the two solvents and with benzene.
benzene is ∼kdiff. As shown above, all nucleophiles, including-
MeCN and TFE, react with this intermediate at a rate (1kNuH
)
107 M-1 s-1 with 2,3-dimethyl-2-butene (N ) -0.96)2e while
within a factor of 5 from kdiff. Cation 11+ is a completely
unselective probe, and could be taken as a model (easier to
monitor) of alkyl carbocations.10b
3
the corresponding values for 1 are 1.7 × 108 and 2.9 × 108
M-1 s-1
.
The compressed range precludes applying a treatment of the
quality of that done by Mayr with benzhydryl cations, where
the rate of trapping varied by >6 orders of magnitude. Still,
the rates are not uniform with phenyl cations, e.g., pyrrole (20)
reacts 50 times faster than pyridine (30), aniline (16) 11 times
faster than n-propylamine (31), and a substituted diene (28) five
times faster than a monosubstituted alkene (22) and ten times
faster than a monosubstituted alkyne (21). This selectivity is
sufficient for preparative purposes in both intra- and intermo-
lecular competitions. As for the dependence on N, one can see
from Figure 3 that π-nucleophiles and amines lie in two
separated areas, within each of which there is a modest increase
On the other hand, when exciting N,N-dimethyl-4-chloroa-
niline (3), ISC to the triplet precedes fragmentation that thus
gives the triplet cation (this is the lowest lying spin state of 1,
∆EST ) 12.9 kcal/mol).6 Despite the predicted E . 10, in this
case the reactivity is not uniform and intermolecular selectivity
was observed. Thus, within the accessible window (a lower limit
is given by the reaction with 3) there is no significant
(irreversible)10a reaction with alcohols or with acetonitrile.
Rather, π-nucleophiles as well as better nitrogen-centered
nucleophiles, such as amines, are selectively arylated with no
interference by the solvent (thus, with such nucleophiles 3kNuH
g 103
×
3kMeCN); likewise, silane 29 transfers hydride as
3
of log kNuH with N.
expected for a σ-nucleophile.
Correlation with Parameter N. A precise evaluation requires
the use of the (nucleophile-dependent) slope parameters s,
introduced by Mayr (see eq 2) for a better correlation. This often
can be neglected, since s has roughly the same value within a
chemical class and for benzhydryl cations the fast increase of
log k with N limits the substrates for which measurable data
are obtained to a single class. This is not the case here, where
a single electrophile is tested with nucleophiles varying from
aromatics to amines.12 Thus, the (log 3kNuH)/s values (see Table
2) were plotted vs N in Figure 4.13 Since for amines this value
is about a half of that of aromatics (s 0.65 vs 1.2-1.3), this has
the effect of enhancing the amines values.
The relative rates of the nucleophiles tested span a factor of
102.11a When considering also nonreacting MeCN and TFE a
105 span results, as opposed to the change by only a factor of
5 for the same reagents with the singlet. We had previously
shown11 that the related triplet 4-methoxyphenyl cation reacted
with benzene with a rate constant of about 1 × 108 M-1 s-1. If
3
we assume that the reaction of 1+ with iodide occurs at the
3
diffusion controlled rate, kI ) 1.2 × 1010 M-1 s-1, one obtains
3kNuH ) 1.7 × 108 M-1 s-1 for the reaction with benzene, which
well fits with what is observed with the methoxy analogue. Thus,
-
3
the above ratios were converted into rate constants, kNuH, on
this basis (see Table 2).
A consistent, if moderate, increase of the (log 3kNuH)/s values
3
The constants kNuH are higher than those with benzhydryl
3
for phenyl cation 1 over a very large range of 22 N units can
cations and exhibit a limited dependence on the N parameter,
varying by only 2 orders of magnitude in correspondence to a
change of 22 N units. As an example, with the most reactive of
benzhydryl cations, (4-ClC6H4)2CH+ (E ) 6.02), kNuH increases
from 4 × 10-4 M-1 s-1 with benzene (N ) -6.29) to 8.9 ×
be detected and a linear fitting including both the values of
π-nucleophiles (omitting 14 and 19) and those of amines
(including pyridine) is possible (see line a in Figure 4, the σ
donor 29 was also omitted). However, this involves a much
(11) (a) Computational work has shown that triplet cation 31 first forms
a single bonded (triplet) adduct with alkenes that then undergoes ISC and
evolves to the final products, see ref 5a; we assume that the rate-determining
step is formation of the initial adduct. (b) Dichiarante, V.; Dondi, D.; Protti,
S.; Fagnoni, M.; Albini, A. J. Am. Chem. Soc. 2007, 129, 5605.
(12) A (log k)/s vs N plot is used when a large span of N values is covered
by several electrophiles, see ref 2e.
(13) Unfortunately the s values were not known for all of the compounds
tested, and in some cases these were estimated from those of structurally
analogous nucleophiles (see footnotes to Table 2).
J. Org. Chem, Vol. 73, No. 4, 2008 1287

Dichiarante et al.
SCHEME 3. More (a) and Less (b) Favored
Nucleophile-Electrophile Interactions
behaves as a less strong electrophile (E ) 8.11) than would be
expected from the affinity with the methyl anion (E ) 27.7).15
Using eq 12 well reproduces a characteristic that has been
noted in the study of phenyl cations,5 viz., that the reaction rate
with amines is slower than that with π-nucleophiles, whereas
the contrary is true with benzhydryl cations. This is because
amines have a small s and large N (the reverse applies to
π-nucleophiles). Therefore, the advantage of having a high E,
as is the case for 31, is in part lost since the contribution by the
sE term increases less than that with π-nucleophiles and likewise
the scaling factor e < 1 limits the increase of the seN term for
strong nucleophiles (large N). As an example, the expected
values of log 3kNuH for the reaction with 31 according to eq 12
are 8.60, 9.64, and 8.30 for 2,3-dihydrofuran, pyrrole, and
pyrrolidine, whereas these are 3.93, 4.63, and 9.92 for the
reaction of a 4,4′-dimethoxybenzhydryl cation (E ) 0) with the
same compounds according to eq 2.
lower than unitary dependence on N (0.33) and then an E value
of 8.11 is evaluated
(log 3kNuH)/s ) 8.11 + 0.33N
(12)
For the sake of comparison, data by Mayr for two benzhydryl
cations, viz. (4-ClC6H4)2CH+ (E ) 6.02, line b in Figure 4)
and the less strong electrophile (4-Me2NC6H4)2CH+ (E -7.02,
line c in Figure 4), are also reported in Figure 4 and exhibit the
behavior expected from eq 2, unitary slope until kdiff is reached
and then a plateau.
Comparison with Other Reactions. The proposal that with
phenyl cations eq 2 can be applied provided that a factor e
limiting the contribution by N is introduced (eq 14) acquires
log k ) s(E + eN)
(14)
We are somewhat reluctant to draw an inference from this
behavior, because of the limited range of the measured rates
significance in relation to the recent report by Mayr that
application of eq 2 to the solvolysis of S-methyldibenzothiophe-
nium ion, that is a SN2 reaction, required a reduction of the
contribution by N (by a factor 0.6, these data are reported in
Figure 4 for the sake of comparison, line d) and an even lower
contribution (ca. 0.45) seemed to fit some SN2 reactions of
methyl iodide (Scheme 3b).1a On the basis of these results, Mayr
proposed generalized eq 15, including both an electrophile- and
a nucleophile-dependent s factor (of which eq 2 was a particular
and their proximity to kdiff,
14 as well as the considerable scatter
of the data (expected in such a limited range). If the dependence
is genuine, a hypothesis for low slope of line a in Figure 4
(compare with line e that would be expected for a unitary
3
dependence on N, (log kNuH)/s ) 8.11 + N, also reported in
Figure 4) can be formulated. Indeed, the characteristics of triplet
31, viz., (i) that E is much smaller than for 11, so that, contrary
to that case, reactions do not occur uniformly at the diffusion-
controlled rate and (ii) the limited increase of the rate of reaction
of 31 with N (weighting factor e ) 0.33) in contrast to the unitary
slope with benzhydryl cations, are both explained by the
different electronic structure of these intermediates.
log k ) sEsN(E + N)
(15)
case) for describing all of the nucleophile-electrophile com-
binations. As seen above, with the present aminophenyl cation
(in the triplet state) the simplified form does not apply. We find
more appropriate to use eq 14, with the weighting factor e, rather
than eq 15, since it expresses more directly the rationalization
based on the interaction of NuH with a semifilled orbital. The
reduced dependence on N observed in SN2 reactions may
likewise be explained by the less accessible (σ*) orbital involved
in the electrophile. Further cases are present in the literature,
e.g., the selectivity in the addition of nucleophiles to a quinone
methide has been found to be twice as much than that for the
reaction with methyl iodide.16
As indicated in Chart 2, singlet cation 11 (π6σ0 orbital
population) has an empty (σ) orbital and stabilization in the
interaction with nucleophiles is fully enjoyed (Scheme 3a). In
this case, E is probably well represented by that calculated from
methyl anion affinity (E ) 30.9), although leveling to the
diffusion limit only allows an estimate for E > 18 from the
fact that the reactions with benzene (N ) -6.39) and MeCN
(N probably lower) are still diffusion controlled or close to it.
3
In contrast, triplet cation 1 has a π5σ1 orbital population and
the charge delocalized on the ring and the amino group.6d It
thus resembles a triplet (diradicalic) carbene rather than a
localized carbocation.6d The nucleophile thus interacts with a
half-filled, rather than with an empty orbital (and forms a
diradical rather than a closed-shell end product, see Scheme 3b
and eq 13).11a
Conclusion
In conclusion, a divalent cation, 4-dimethylaminophenyl
cation, has been tested as a probe in the reaction with a series
of nucleophiles. The observed behavior depends on multiplicity.
The singlet (E > 18) reacts with any nucleophile at a rate equal
or close to the diffusion constant, and its smooth photochemical
generation from the diazonium salt may make it an experimen-
tally convenient model of alkyl carbocations. The triplet, on
the other hand, has been found to react with various π-, n-, and
Ar+(vv) + Nu: f Ar+(v)-Nu(v)
(13)
Accordingly, the stabilization when interacting with the
nucleophile is reduced. The reaction does not occur when the
nucleophile center is an alcohol oxygen, and when it does occur,
as with amines as well as σ- and π-nucleophiles, the cation
(15) Notice further that the approaching path of the nucleophile to the
triplet cation is different. As an example, with alkenes, a single bond is
first formed leading to a diradical cation, whereas with the singlet cation a
closed shell phenonium ion is the first intermediate.5a,11
(16) Richard, J. P.; Poteva, M. M.; Crugeiras, J. J. Am. Chem. Soc. 2000,
122, 1664.
(14) As a matter of fact, the use of eq 2 is not recommended2c where E
+ N > 8, but for the reasons presented in the text we feel that the small
dependence on N observed is meaningful in this case.
1288 J. Org. Chem., Vol. 73, No. 4, 2008

Establishing Electrophilicity-Nucleophilicity Relations
σ-nucleophiles, at rates that were high (108-1010 M-1 s-1) but
not flattened on kdiff. Importantly, this cation does not react with
alcohols, but apart from this, the observed reactions are the same
as in the case of benzhydryl ions, with C-C, C-H, and
C-nitrogen bond formation. Application of Mayr’s equation
to amines and to (most of) π-nucleophiles is possible by
introducing a scaling factor (0.33) for the nucleophilicity
parameter, supporting that also in this case the electrophile-
nucleophile interaction is the rate-determining step, with the
value E ) 8.11. The N contribution is reduced because a half-
filled, rather than an empty, orbital is involved.15
Photochemical Reactions of 2. Solutions of 4-(N,N-dimethy-
lamino)benzendiazonium tetrafluoroborate (0.05 M) containing the
nucleophile as well as an internal standard (dodecane 0.5 µL per
mL) in 5 mL of MeCN in a quartz test tube were flushed with
purified nitrogen and irradiated at 20 °C by means of 6×15W lamps
(emission centered at 310 nm) for 10 min. The residual diazonium
salt was trapped by addition of some drops of a basic aqueous
solution of â-naphthol. Dilute aqueous NaHCO3 was added. The
mixture was extracted by diethyl ether, and the separated organic
phases were brought to a fixed volume and analyzed by GC on the
basis of calibration curves.
Photochemical Reactions of 3. Solutions of 4-chloro-N,N-
dimethylaniline (0.05 M) containing the nucleophile (1 M), NaI (5
× 10-3 to 0.2 M), and triethylamine (5 × 10-3 M, in order to buffer
the acidity liberated) were flushed, irradiated as above, and analyzed
by GC on the basis of calibration curves.
The introduction of a scaling factor for the fast reactions of
cations proposed here follows related observations,2a,16 in
particular Mayr’s finding that N < 1 is required when using
the N scale for the (much slower) SN2 reactions, where again
the electrophile interacts with a different (σ*) orbital. With this
proviso, a single set of parameters E, N, and s can be used
independently on the mechanism over an ever increasing range
of rate constants, but changing the nature of the electrophilic
probe may require the introduction of a characteristic parameter
e tuning the N contribution. This has a unitary value when the
structure of the electrophile strongly favors the interaction (π-
type LUMO, as with benzhydryl cations and with the other
planar, nonhindered electrophiles shown in Chart 1, as well as
Each determination is the average of 4 to 5 independent
measurements. Double reciprocal plots of N,N-dimethyl-4-
iodoaniline-1 vs NaI-1 drawn over four or five NaI concentrations
for each nucleophile gave linear plots with constant intercept
3
3
-
-
((12%). The slope/intercept ratio corresponded to kNuH/ kI [I ].
The relative rate values were converted into absolute rate constants
3
10
by assuming kI ) 1.2 × 10 M-1 s-1
.
-
Calculations. The energy difference ∆Eo for the reaction between
4-N,N-dimethylaminophenyl cation (singlet and triplet, see coor-
dinates in ref 6d) and methyl anion to give 4-methyl-N,N-
dimethylaniline was calculated at the B3LYP-6-31g(d,p) level by
using the Gaussian 03 package18 and found to be -303.4 kcal/mol
for the singlet and -294.7 kcal/mol for the triplet.
1
with the empty σ orbital in 1), but is otherwise expected to
take a lower value, since the nucleophile-electrophile interac-
tion is in some way hindered in other electrophiles (noncationic
and nonplanar electrophiles, or a partially occupied MO), as
indicated in Scheme 3a,b.
Acknowledgment. Dr. Daniele Dondi from this University
is heartily thanked for carrying out the above calculations. Partial
support of this work by Ministero dell’Universita` e della Ricerca,
Rome, is gratefully acknowledged. Prof. H. Mayr from the
Munich University is thanked for useful comments.
Experimental Section
General. The starting materials 4-N,N-dimethylaminophenyl-
diazonium tetrafluoborate (2)7 and 4-chloro-N,N-dimethylaniline
(3)6d were prepared according to published procedures. Solvents,
reagents, and compound 6 were high-purity grade commercial
samples and were used as received. The preparation and purification
of photoproducts used for the calibration curves of the photoreac-
tions has been reported in previous work (4-10),6d,17 while
compound 4′ was prepared and purified as reported below.
4-(2,2,2-Trifluoroethoxy)-N,N-dimethylaniline (4′). 4-(N,N-
Dimethylamino)benzendiazonium tetrafluoroborate (587 mg, 2.5
mmol, 0.25 M) was dissolved in 10 mL of TFE. The solution was
flushed with nitrogen and irradiated at 310 nm for 4.5 h. After
removing the solvent, the residue was purified by column chro-
matography (cyclohexane/ethyl acetate 99:1 with 0.2% NEt3 added),
affording 285 mg of ether 4′ (colorless solid, 52% yield). 4′: mp
67-69 °C. 1H NMR (CDCl3) δ 2.80 (s, 6H), 4.30 (q, 2H, J ) 8.3
Hz), 6.75 (AA′BB′, 2H), 6.90 (AA′BB′, 2H). 13C NMR (CDCl3) δ
41.2 (CH3), 67.1 (q, CH2, J ) 35 Hz), 114.1 (CH), 116.3 (CH),
123.4 (q, J ) 276 Hz), 146.9, 149.5. IR (neat) ν/cm-1 1082, 1156,
1247, 1518, 1637, 3440. Anal. Calcd for C10H12F3NO: C 54.79, H
5.52. Found: C 54.9, H 5.1.
Supporting Information Available: NMR spectra of compound
4′ and kinetic data. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO7019509
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J. Org. Chem, Vol. 73, No. 4, 2008 1289