Nucleophilicities of nitroalkyl anions

Article abstract of DOI:10.1021/jo048773j

The kinetics of the reactions of eight nitroalkyl anions (nitronate anions) with benzhydrylium ions and quinone methides in DMSO and water were investigated photometrically. The second-order rate constants were found to follow a Ritchie constant selectivi

Full text of DOI:10.1021/jo048773j

Nu cleop h ilicities of Nitr oa lk yl An ion s
Thorsten Bug, Tadeusz Lemek, and Herbert Mayr*
Department Chemie und Biochemie der Ludwig-Maximilians-Universita¨t Mu¨nchen,
Butenandtstrasse 5-13 (Haus F), D-81377 Mu¨nchen, Germany
Herbert.Mayr@cup.uni-muenchen.de
Received J uly 19, 2004
The kinetics of the reactions of eight nitroalkyl anions (nitronate anions) with benzhydrylium ions
and quinone methides in DMSO and water were investigated photometrically. The second-order
rate constants were found to follow a Ritchie constant selectivity relationship with slightly smaller
selectivities than those observed previously for other carbanions and O or N nucleophiles. Evaluation
of the kinetic data by the correlation equation log k (20 °C) ) s(N + E) yields the nucleophilicity
parameters (N), which allow a comparison of the nucleophilicities of nitronates with those of other
classes of compounds. Although the aliphatic nitronates 1a -c are more nucleophilic than the
aromatic representatives 1d -h in DMSO, hydration reduces the nucleophilicities of aliphatic
nitronates by a factor of 1 million, which is considerably greater than the reduction of the reactivities
of the aromatic nitronates with the consequence that aromatic nitronates are more nucleophilic in
water than aliphatic ones. The nucleophilic reactivities of nitronates are only slightly affected by
substituent variation in DMSO and even less so in aqueous solution, which is considered to be the
reason for the unusual rate equilibrium relationships, the so-called nitroalkane anomaly. Outer-
sphere electron transfer does not occur in any of the reactions that were investigated.
SCHEME 1. P r oton a tion of Ar yl Nitr on a tes in
Wa ter
In tr od u ction
Relationships between nucleophilicity and basicity
belong to the fundamental concepts of the electronic
theory of organic chemistry.1,2 Thus, substituents R that
increase the basicity of carbanions are generally assumed
to also increase the nucleophilicity.2,3
This and related phenomena are termed nitroalkane
anomaly.5 As a consequence, in contrast to common
practices in preparative carbanion chemistry, pKaH values
cannot be employed for estimating the relative nucleo-
philicities of nitroalkyl anions, which are of great impor-
tance as reagents in organic synthesis.6
Previously, we have demonstrated that eq 1 can be
used for developing a comprehensive nucleophilicity
scale, including n-, π-, and σ-nucleophiles,7 and we have
suggested employing benzhydrylium ions and structur-
R-CH2Q + EX f R-CH2E + XQ
It has long been known, however, that acceptor groups
in the m- and p-positions of phenylnitromethyl anions
reduce basicity (as expected) but, at the same time,
increase the rate of conversion of the nitroalkyl anions
into the corresponding acids (kf in Scheme 1).4
(1) Brønsted, J . N.; Pedersen, K. Z. Phys. Chem. 1924, 108, 185-
235.
(2) Bordwell, F. G.; Cripe, T. A.; Hughes, D. L. In Nucleophilicity;
Harris, J . M., McManus, S. P., Eds.; American Chemical Society:
Washington, DC, 1987.
(5) (a) Bernasconi, C. F.; Ali, M.; Gunter, J . C. J . Am. Chem. Soc.
2003, 125, 151-157. (b) Yamataka, H.; Ammal, S. C. Arkivoc 2003,
59-68. (c) Eliad, L.; Hoz, S. J . Phys. Org. Chem. 2002, 15, 540-543.
(d) Yamataka, H.; Mustanir; Mishima, M. J . Am. Chem. Soc. 1999,
121, 10223-10224. (e) Beksic, D.; Betran, J .; Lluch, J . M.; Hynes, J .
T. J . Phys. Chem. A 1998, 102, 3977-3984. (f) Erden, I.; Keefe, J . R.;
Xu, F. P.; Zheng, J . B. J . Am. Chem. Soc. 1993, 115, 9834-9835. (g)
Bernasconi, C. F.; Paschalis, P. J . Am. Chem. Soc. 1989, 111, 5893-
5902. (h) Albery, W. J .; Bernasconi, C. F.; Kresge, A. J . J . Phys. Org.
Chem. 1988, 1, 29-31. (i) Pross, A.; Shaik, S. S. J . Am. Chem. Soc.
1982, 104, 1129-1130. (j) Agmon, N. J . Am. Chem. Soc. 1980, 102,
2164-2167. (k) Keeffe, J . R.; Morey, J .; Palmer, C. A.; Lee, J . C. J .
Am. Chem. Soc. 1979, 101, 1295-1297. (l) Kresge, A. J . Can. J . Chem.
1974, 52, 1897-1903. (m) Goumont, R.; Magnier, E.; Kizilian, E.;
Terrier, F. J . Org. Chem. 2003, 68, 6566-6570. (n) Terrier, F.;
Moutiers, G.; Pelet, S.; Buncel, E. Eur. J . Org. Chem. 1999, 1771-
1774. (o) Moutiers, G.; Peignieux, A.; Terrier, F. J . Chem. Soc., Perkin
Trans. 2 1998, 2489-2495. (p) Moutiers, G.; Thuet, V.; Terrier, F. J .
Chem. Soc., Perkin Trans. 2 1997, 1479-1486. (q) Marcus, R. A. J .
Am. Chem. Soc. 1969, 91, 7224-7225.
(3) (a) Bates, R. B.; Ogle, C. A. In Carbanion Chemistry-Reactivity
and Structure Concepts in Organic Chemistry; Hafner, K., Lehn, J .-
M., Rees, C. W., Schleyer, P. von R., Trost, B. M., Zahradnik, R., Eds.;
Springer-Verlag: Berlin, 1983; Vol. 17. (b) Buncel, E.; Dust, J . M.
Carbanion Chemistry-Structures and Mechanism; Oxford: New York,
2003. (c) Snieckus, V. Advances in Carbanion Chemistry; J AI: Green-
wich, CT, 1992 and 1996; Vols. 1 and 2. (d) Heathcock, C. H.;
Winterfeldt, E.; Schlosser, M. In Modern Synthetic Methods-Topics in
Carbanion Chemistry; Scheffold, R., Ed.; VHCA and VCH: Basel,
Switzerland, and Weinheim, Germany, 1992. (e) Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Pattenden, G., Eds.;
Pergamon Press: Oxford, 1991; Vol. 3, Chapters 1.1-1.7.
(4) (a) Fukuyama, M.; Flanagan, P. W. K.; Williams, F. T., J r.;
Frainier, L.; Miller, S. A.; Shechter, H. J . Am. Chem. Soc. 1970, 92,
4689-4699. (b) Bordwell, F. G.; Boyle, W. J ., J r.; Yee, K. C. J . Am.
Chem. Soc. 1970, 92, 5926-5932. (c) Bordwell, F. G.; Boyle, W. J ., J r.
J . Am. Chem. Soc. 1975, 97, 3447-3452. (d) Bernasconi, C. F.;
Wiersema, D.; Stronach, M. W. J . Org. Chem. 1993, 58, 217-223.
10.1021/jo048773j CCC: $27.50 © 2004 American Chemical Society
Published on Web 10/07/2004
J . Org. Chem. 2004, 69, 7565-7576
7565

Bug et al.
TABLE 1. Electr op h ilicity P a r a m eter s E a n d Ritch ie
P a r a m eter s (log k0) of th e Refer en ce Electr op h iles
Em p loyed for Deter m in in g th e Nu cleop h ilicities of
Nitr oa lk yl An ion s 1a -h
SCHEME 2
Resu lts
P r ep a r a tive In vestiga tion s. As discussed by See-
bach,14 nitronate ions cannot be readily C-alkylated by
ordinary alkyl halides. In contrast, good yields of the
C-alkylation products (3a -g) were obtained when solid
benzhydrylium tetrafluoroborate (2a -BF4-) was added to
solutions of the potassium nitronates [(1a -g)-K+] in
aqueous acetonitrile (Scheme 2).
The less-electrophilic benzhydrylium tetrafluoroborate
2c-BF4- was demonstrated to react analogously with 1a
to yield 87% of the addition product 4a .
Only moderate yields of products 5f-h were isolated
when 1b-NBu4+ was combined with the quinone methides
2f-h in DMSO (Scheme 3).13
a
b
d
In water, from ref 11. From ref 8. c From ref 9. In DMSO,
from ref 12. e In DMSO, from ref 13.
SCHEME 3
ally related quinone methides as reference electrophiles8-10
(Table 1)
log k (20 °C) ) s(N + E)
where k is the second-order rate constant in M-1 s-1, s is
the nucleophile-specific slope parameter, is the
(1)
N
nucleophilicity parameter, and E is the electrophilicity
parameter.
(6) (a) Nitro Compounds; Feuer, H., Nielsen, A., Eds.; Wiley: New
York, 1990. (b) Seebach, D.; Colvin, E. W.; Lehr, F.; Weller, T. Chimia
1979, 33, 1-18. (c) Ono, N. The Nitro Group in Organic Synthesis;
Wiley-VCH: Weinheim, Germany, 2001. (d) Denmark, S. E.; Cotell,
J . J . In The Chemistry of Heterocyclic Compounds; Padwa, A., Pearson,
W. H., Eds.; Wiley: New York, 2002; Vol. 59, pp 83-167. (e) Torssell,
K. B. G. In Nitrile Oxides, Nitrones, and Nitronates in Organic
Synthesis; Feuer, H., Ed.; VCH: Weinheim, Germany, 1988; pp 129-
270. (f) Tartakovsky, V. A.; Ioffe, S. L.; Dilman, A. D.; Tishkov, A. A.
Russ. Chem. Bull. 2001, 50, 1936-1948. (g) Schlosser, M. In Organo-
metallics in Synthesis-A Manual; Schlosser, M., Ed.; Wiley: Chichester,
U.K., 2002; pp 1-352.
(10) Mayr, H.; Kempf, B.; Ofial, A. R. Acc. Chem. Res. 2003, 36, 66-
77.
(11) Minegishi, S.; Mayr, H. J . Am. Chem. Soc. 2003, 125, 286-
295.
(12) Remennikov, G.; Mayr, H., unpublished results.
(13) Lucius, R. Kinetische Untersuchungen zur Nucleophilie stabi-
lisierter Carbanionen, Dissertation, Ludwig-Maximilians-Universita¨t,
Mu¨nchen, Germany, 2001.
(14) (a) Seebach, D.; Lehr, F. Helv. Chim. Acta 1979, 62, 2239-2257.
(b) On the ambident reactivity of nitronate anions, see also: Linton,
B. R.; Goodman, M. S.; Hamilton, A. D. Chem. Eur. J . 2000, 6, 2449-
2455.
(7) Mayr, H.; Patz, M. Angew. Chem. 1994, 106, 990-1010; Angew.
Chem., Int. Ed. Engl. 1994, 33, 938-957.
(8) Mayr, H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.; J anker,
B.; Kempf, B.; Loos, R.; Ofial, A. R.; Remennikov, G.; Schimmel, H. J .
Am. Chem. Soc. 2001, 123, 9500-9512.
(9) Lucius, R.; Loos, R.; Mayr, H. Angew. Chem. 2002, 114, 97-
102; Angew. Chem., Int. Ed. 2002, 41, 91-95.
7566 J . Org. Chem., Vol. 69, No. 22, 2004

Nucleophilicities of Nitroalkyl Anions
As shown in Schemes 2 and 3, product studies, includ-
ing the full characterization of compounds 3a -g, 4a , and
5f-h (see Supporting Information), were only performed
for representative combinations of nitronate anions 1 and
electrophiles 2 because variations of the remote aryl sub-
stituents were not expected to affect the types of products.
Kin etic In vestiga tion s
Gen er a l. All of the reactions investigated in this work
have been studied photometrically following the decay
of electrophiles 2a -i (absorption maxima at λmax ) 371-
630 nm). Nitroalkyl anions 1a -h were generally em-
ployed in large excess over the electrophiles (see Tables
S1-S49 in the Supporting Information). As a conse-
quence, the concentrations of 1a -h remained almost
constant throughout the reactions and gave rise to
pseudo-first-order kinetics with an exponential decay of
the concentrations of the electrophiles 2 (eq 2).
F IGURE 1. Determination of the second-order rate constant
(k2,C-) for the reaction of 2f with deprotonated nitromethane
[1a -(P2-t-Bu)-H+] in DMSO at 20 °C.
TABLE 2. Secon d -Or d er Ra te Con sta n ts (k2,C-) for th e
Rea ction s of Nitr oa lk yl An ion s 1a -h w ith Qu in on e
Meth id es or Ben zh yd r yliu m Tetr a flu or obor a tes in DMSO
a t 20 °C
-d[2]/dt ) k1Ψ[2]
(2)
Kin etic In vestiga tion s in DMSO. Dimethyl sulfox-
ide solutions of nitroalkyl anions 1a -h were generated
by deprotonation of the corresponding CH acids with
phosphazene bases P2-t-Bu, BEMP, and DBU.15
In previous work, we have shown that ion pairing or
variable ion strengths did not affect the kinetics of the
reactions of stabilized carbanions with quinone methides
or benzhydrylium ions in DMSO.9,16 This behavior was
explained by the low values of the ion-pair association
constants17 in solvents of high permittivity (ꢀDMSO ) 46;
from ref 18).
As shown in Figure 1 and for all other systems in the
Supporting Information, plots of k1Ψ versus nitroalkyl
anion concentration were generally linear, with almost
zero intercepts. One can, therefore, conclude that the
nature of the nucleophiles (free or paired ions) did not
significantly change within the concentration range
investigated. The slopes of these correlations gave the
second-order rate constants (k2,C-) that are listed in
Table 2.
(15) Schwesinger, R.; Schlemper, H.; Hasenfratz, C.; Willaredt, J .;
Dambacher, T.; Breuer, T.; Ottaway, C.; Fletschinger, M.; Boele, J .;
Fritz, H.; Putzas, D.; Rotter, H. W.; Bordwell, F. G.; Satish, A. V.; J i,
G.-Z.; Peters, E.-M.; Peters, K.; von Schnering, H. G.; Walz, L. Liebigs
Ann. Chem. 1996, 1055-1081. P2-t-Bu: 1-(tert-butylimino)-1,1,3,3,3-
pentakis(dimethylamino)-1λ5,3λ5-diphosphazene, pKBH
) 21.4 (in
+
a
b
In DMSO. For abbreviations, see ref 15. c From ref 17.
DMSO), CAS Registry No. 111324-03-9. BEMP: (2-tert-butylimino-
1,3-dimethyl-2λ5-[1,3,2]diazaphosphinan-2-yl)diethylamine, pKBH
≈
+
From ref 19. e From ref 20. f From ref 16. From ref 21.
d
g
16.5 (in DMSO), CAS Registry No. 98015-45-3. DBU: 1,8-diazabicyclo-
+
[5.4.0]undec-7-ene, pKBH ≈ 13.9 (in DMSO), CAS Registry No. 6674-
22-2.
Kin etic In vestiga tion s in Wa ter . In the reactions
(16) Lucius, R.; Mayr, H. Angew. Chem. 2000, 112, 2086-2089;
Angew. Chem., Int. Ed. 2000, 39, 1995-1997.
(17) Olmstead, W. N.; Bordwell, F. G. J . Org. Chem. 1980, 45, 3299-
3305.
(18) Reichardt, C. Solvents and Solvent Effects in Organic Chemistry,
3rd ed.; Wiley-VCH: Weinheim, Germany, 2003.
of nitroalkyl anions 1a -h in water, competing reactions
of the benzhydrylium ions with hydroxide and water have
to be considered. The observed pseudo-first-order rate
constants (k1Ψ,obs) reflect the sum of the reactions of the
J . Org. Chem, Vol. 69, No. 22, 2004 7567

Bug et al.
TABLE 3. In flu en ce of th e Con cen tr a tion of Hyd r oxid e on th e Secon d -Or d er Ra te Con sta n ts k 2 of th e Rea ction s of
-
2b-BF 4 w ith th e P ota ssiu m Sa lt of Nitr om eth a n e (1a )
entry
[2b-BF4-]0 (M)
[OH-]0 (M)
[CH3NO2]0 (M)
[1a -K+] (M)
k
1Ψ (s-1
)
k2 (M-1 s-1
)
1
2
3
4
5
6
2.34 × 10-5
2.55 × 10-5
2.53 × 10-5
2.31 × 10-5
2.48 × 10-5
2.20 × 10-5
7.76 × 10-5
2.11 × 10-4
4.19 × 10-4
7.66 × 10-4
1.23 × 10-3
1.46 × 10-3
8.13 × 10-4
2.21 × 10-3
4.39 × 10-3
8.02 × 10-3
1.29 × 10-2
1.53 × 10-2
6.35 × 10-5
1.95 × 10-4
4.02 × 10-4
7.49 × 10-4
1.21 × 10-3
1.44 × 10-3
8.29 × 10-3
2.11 × 10-2
4.11 × 10-2
7.85 × 10-2
1.29 × 10-1
1.52 × 10-1
1.05 × 102 a
1.03 × 102 b
9.78 × 101 c
7
8
9
10
11
12
9.79 × 10-6
9.79 × 10-6
9.79 × 10-6
9.79 × 10-6
9.79 × 10-6
9.79 × 10-6
2.54 × 10-3
2.54 × 10-3
2.54 × 10-3
2.54 × 10-3
2.54 × 10-3
2.54 × 10-3
3.66 × 10-4
5.48 × 10-4
7.31 × 10-4
9.14 × 10-4
1.37 × 10-3
1.83 × 10-3
3.40 × 10-4
5.07 × 10-4
6.71 × 10-4
8.33 × 10-4
1.22 × 10-3
1.56 × 10-3
3.44 × 10-2
4.93 × 10-2
6.77 × 10-2
8.49 × 10-2
1.22 × 10-1
1.60 × 10-1
13
14
15
16
17
18
9.79 × 10-6
9.79 × 10-6
9.79 × 10-6
9.79 × 10-6
9.79 × 10-6
9.79 × 10-6
5.07 × 10-3
5.07 × 10-3
5.07 × 10-3
5.07 × 10-3
5.07 × 10-3
5.07 × 10-3
3.66 × 10-4
5.48 × 10-4
7.31 × 10-4
9.14 × 10-4
1.37 × 10-3
1.83 × 10-3
3.54 × 10-4
5.29 × 10-4
7.04 × 10-4
8.79 × 10-4
1.31 × 10-3
1.74 × 10-3
2.90 × 10-2
4.58 × 10-2
6.14 × 10-2
7.73 × 10-2
1.22 × 10-1
1.64 × 10-1
a
b
Calculated from the slopes of plots of k1Ψ (eq 4) vs [1a ] for entries 1-6. Calculated from the slopes of plots of k1Ψ (eq 4) vs [1a ] for
entries 7-12. c Calculated from the slopes of plots of k1Ψ (eq 4) vs [1a ] for entries 13-18.
SCHEME 4. C- a n d O-Alk yla tion of Nitr on a tes
benzhydrylium ions with the nitroalkyl anion (k1Ψ,C-),
OH- (k1Ψ,OH-), and water (k1Ψ,W) (eq 3).
k1Ψ,obs ) k1Ψ,C- + k1Ψ,OH- + k1Ψ,W
) k2,C-[C-] + k -[OH-] + k
(3)
2,OH
1Ψ,W
[C-] is the concentration of the nitroalkyl anion, which
was generated from the CH acid with KOH. The concen-
trations of the nitroalkyl anions [C-] and of the hydroxide
resulting second-order rate constants agree within (3%
(last column in Table 3), which reflects the error limits
of our experiments.
Though the products that were isolated from the
combination of benzhydrylium ions with nitroalkyl anions
(Scheme 2) show the formation of carbon-carbon bonds,
one cannot exclude a priori the initial attack of benzhy-
drylium ions at the oxygen of the nitro group and the
successive rearrangement into the nitro compound, as
illustrated in Scheme 4.
[OH-] are calculated22 from [OH-]0, [CH acid]0, and pKaH
,
as described in the Supporting Information. With the
published k2,OH- values11 and the calculated concentra-
tions [OH-], the partial pseudo-first-order rate constants,
-
-
-
k1Ψ,OH ) k2,OH [OH ], can be calculated.
k
1Ψ ) k1Ψ,obs - k2,OH-[OH-] ) k -[C-] + k
(4)
2,C
1Ψ,W
According to eq 4, the slopes of the plots of k1Ψ versus
[C-] correspond to the second-order rate constants k2,C-.
As explicitly shown in the Supporting Information, the
intercepts, which correspond to the reactions of the
benzhydrylium ions with water, are negligible, in accord
with their directly measured reactivities toward water.11
To explicitly determine the influence of the hydroxide
concentration on the reactivities of the nitroalkyl anions,
Initial O-alkylation with the intermediate accumula-
tion of the nitronates of 6 was definitely ruled out for
the reaction of nitroalkyl anion 1f with benzhydrylium
ion 2a (Figure 2).
A combination of equimolar amounts of 1f and 2a in
water resulted in a decay of the absorptions of 1f (λmax
)
380 nm, log ꢀ ) 4.14)23,24 and 2a (λmax ) 604 nm)11 and
the appearance of a new absorption at λmax ) 261 nm.
The eventual intermediate (6f) possesses a chromophore
similar to that of 8f, the UV spectrum of which has been
reported in the literature.25
-
the reaction of H2CNO2 (1a ) with 2b was studied in
detail. In a first series of experiments (entries 1-6, Table
-
3), the benzhydrylium salt, 2b-BF4 (∼0.02 mM), was
combined with variable amounts of 1a (∼0.06-1.4 mM),
while the ratio of nitromethane/KOH was kept constant
at 10.5. In a second and third series of experiments, the
concentration [2b-BF4-] was kept at 9.79 × 10-3 mM and
at a constant of [OH-]0 ) 2.54 (entries 7-12) and 5.07
mM (entries 13-18), respectively, while the nitromethane
concentration was varied from 0.37 to 1.83 mM. The
Figure 2 shows the absence of a peak between 300 and
350 nm throughout the reaction. For that reason, one can
exclude the formation of significant concentrations of 6f,
which successively rearranges to 3f. While this experi-
ment proves that the rate constants, k2,C- (Table 4), refer
to the C-C bond-forming reactions, we cannot exclude
(19) Bordwell, F. G.; Satish, A. V. J . Am. Chem. Soc. 1994, 116,
8885-8889.
(23) Bernasconi, C. F.; Ni, J . X. J . Am. Chem. Soc. 1993, 115, 5060-
5066.
(20) Lemek, T.; Mayr, H. J . Org. Chem. 2003, 68, 6880-6886.
(21) Keeffe, J . R.; Morey, J .; Palmer, C. A.; Lee, J . C. J . Am. Chem.
Soc. 1979, 101, 1295-1297.
(24) Moutiers, G.; Thuet, V.; Terrier, F. J . Chem. Soc., Perkin Trans.
2 1997, 1479-1486.
(25) Kornblum, N.; Brown, R. A. J . Am. Chem. Soc. 1964, 86, 2681-
(22) Bug, T.; Mayr, H. J . Am. Chem. Soc. 2003, 125, 12980-12986.
2687.
7568 J . Org. Chem., Vol. 69, No. 22, 2004

Nucleophilicities of Nitroalkyl Anions
TABLE 4. Secon d -Or d er Ra te Con sta n ts (k2,C-) for th e
Rea ction s of th e P ota ssiu m Sa lts of Nitr oa lk yl An ion s
1a -h w ith th e Tetr a flu or obor a te Sa lts of Ben zh yd r yliu m
Ion s 2a -c (in H2O, a t 20 °C)
F IGURE 2. Online UV-vis monitoring of the reaction of
nitroalkyl anion 1f with benzhydrylium ion 2a (in water at
20 °C, reaction conditions: 2a /KOH/1f-H ) 1/5/1).
the fast reversible formations of low concentrations of the
O-alkylated intermediates 6.
Discu ssion
Ritch ie Cor r ela tion s. Thirty years ago, Ritchie dem-
onstrated that many combinations of stabilized carbo-
cations with various types of nucleophiles follow the
constant selectivity relationship (eq 5)
log(k/k0) ) N+
(5)
a
In water, from ref 26. b In water, from ref 27. c Calculated from
increments as described in ref 28. Since 1e and 1h are considerably
less basic than OH-, errors in pKaH values by 1-2 units do not
affect the calculated concentrations of the carbanions.
where nucleophiles are characterized by a single elec-
trophile-independent parameter (N+), and log k0 repre-
sents the nucleophile-independent electrophile reactivi-
ties.29
Because cyanide was the only carbon nucleophile
characterized by Ritchie, we have recently investigated
carbanions that are stabilized by two keto, ester, or cyano
groups and reported that their reactivities toward car-
bocations also follow the constant selectivity relationship
(eq 5).22
Least-squares fitting of the rate constants in Table 4,
according to eq 5 using the previously published log k0
parameters11 of benzhydrylium ions, shows systematic
deviations from the correlation lines, which were derived
from the reactions of benzhydrylium ions with O and N
nucleophiles (Figure 3). It should be noted that the
deviation of the data points for 2a and 2c from the drawn
correlation lines is not an artifact. Of course, one might
draw correlation lines going through these points imply-
ing that the secluded data set described in this work
follows a constant selectivity relationship. However, this
would be different from the constant selectivity relation-
ship reported in refs 11 and 22. In Figure 3, the majority
of rate constants for the most-reactive electrophile (2a )
are below the correlation line, while the rate constants
for the least-reactive electrophile (2c) are above the
previously determined correlation line. It is thus indi-
cated that nitroalkyl anions in water are, in general,
slightly less selective toward carbenium ions than O and
N nucleophiles11 and most ester- and keto-substituted
carbanions.22
(26) Turnbull, D.; Maron, S. H. J . Am. Chem. Soc. 1943, 65, 212-
218.
(27) Bordwell, F. G.; Boyle, W. J ., J r. J . Am. Chem. Soc. 1972, 94,
3907-3911.
(28) From SciFinder Scholar 2002: calculated using Advanced
Chemistry Development (ACD) Software Solaris V4.67 (© 1994-2003
ACD).
(29) (a) Ritchie, C. D. Acc. Chem. Res. 1972, 5, 348-354. (b) Ritchie,
C. D. Can. J . Chem. 1986, 64, 2239-2250.
J . Org. Chem, Vol. 69, No. 22, 2004 7569

Bug et al.
F IGURE 5. Correlation of the rate constants (20 °C) for the
reactions of nitroalkyl anions 1a -h with the benzhydrylium
F IGURE 3. Analysis of the rate constants of the reactions of
nitroalkyl anions 1a -h with benzhydrylium cations 2a -c in
water (20 °C) according to the Ritchie formalism (eq 5). The
drawn correlation lines are derived from the reactions of
benzhydrylium ions 2a -c with O and N nucleophiles in ref
11.
-
tetrafluoroborates (2a -c)-BF4 in water toward the electro-
philicity parameters E (data for 1d and 1g not plotted).
F IGURE 6. Correlation of the rate constants (20 °C) for the
reactions of nitroalkyl anions 1a -h with the electrophiles 2
in DMSO toward the electrophilicity parameters E (data for
1c and 1d not plotted).
nitroalkyl anions in water with those of amines, hydrox-
ide, and other carbanions in water, reveals a remarkable
phenomenon. The nucleophilic reactivities of all ni-
troalkyl anions in water that were investigated in this
work are within 1.5 logarithmic units, comparable to
those of hydroxide ions and primary aliphatic amines.
The phenomenon that the aryl-substituted nitroalkyl
anions are slightly more nucleophilic than the alkyl-
substituted representatives, in contrast to the expecta-
tions on the basis of pKaH values, will be discussed below.
F IGURE 4. Comparison of the Ritchie N+ values for ni-
troalkyl anions 1a -h in water with those of other nucleo-
philes: N+ of OH-, H2NNHCONH2, HONH2, CF3CH2O-, and
n-PrNH2 from ref 11, N+ of dimedone and Meldrum’s acid from
ref 22, and N+ of EtNH2 and H2NNH2 from ref 29b.
Cor r ela tion s w ith log k (20 °C) ) s(N + E). A more
comprehensive comparison of nucleophilic reactivities can
be based on eq 1, which differs from Ritchie’s correlation
(eq 5) by the additional nucleophile-dependent slope
parameter s.7-10 Figures 5 and 6 plot the rate constants
(log k) of the reactions of representative nitroalkyl anions
with reference electrophiles (benzhydrylium ions and
While the lower selectivities of nitroalkyl anions 1a -h
can quantitatively be treated by the slope parameter of
eq 1 (see below), the deviations from the Ritchie correla-
tion (eq 5, Figure 3) are small enough that the calculation
of approximate N+ parameters appears to be justified.
Figure 4, which compares the nucleophilic reactivities of
7570 J . Org. Chem., Vol. 69, No. 22, 2004

Nucleophilicities of Nitroalkyl Anions
TABLE 5. Com p a r ison of th e Rea ctivity P a r a m eter s N
a n d s for Nitr oa lk yl An ion s 1a -h in Wa ter a n d DMSO
F IGURE 7. Comparison of the nucleophilicities of nitroalkyl
anions 1a -h in water and DMSO.
ions are 9-11 units smaller in water than those in
DMSO, corresponding to a reduction in the rate constants
by roughly 1 million (depending on the reference elec-
trophile), the solvent effect on the aromatic nitronates
is much smaller (∆N ) 3-6). As a consequence, the
aliphatic nitronate ions, which are the stronger nucleo-
philes in DMSO, are the weaker nucleophiles in water.
Solvation of the more localized charges in 1a -c by
hydrogen bridging in water may account for this finding.
Ha m m ett Cor r ela tion s. Nucleophilic reactivities of
phenolate and benzyl anions usually correlate with the
Hammett-Brown parameter, σ- (direct conjugation of
the lone pair at the reaction center with the variable
substituents).30 Accordingly, the reactions of carbanions
1d -h with various electrophiles in DMSO follow the
Hammett σ-correlations with small negative reaction
constants (F ≈ -1.0), though with low correlation coef-
ficients, indicating that only a small part of the negative
charge in the nitronates is delocalized by the aromatic
ring (Figure 8).
quinone methides) in water and DMSO, respectively,
against the corresponding E parameters.
Evaluation of the correlation lines shown in Figures 5
and 6 according to eq 1 yields the N and s parameters
for nitroalkyl anions 1a -h in water and DMSO, as listed
in Table 5.
Table 5 indicates that the slopes s are generally
somewhat greater in DMSO than in aqueous solution.
The differences in s are so small, however, that a detailed
analysis of the slope parameters does not appear to be
meaningful at present. The small values of s (0.46-0.56)
for the nitroalkyl anions in water, which are smaller than
those of most other nucleophiles so far investigated,
reflect the previously discussed deviations of the data
points from the Ritchie correlations in Figure 3.
Str u ctu r e-Rea ctivity Rela tion sh ip s. Though the
relative reactivities of the nitroalkyl anions slightly
depend on the nature of the electrophile because of the
differences in s, some general trends can be derived from
Figure 7.
In DMSO, aromatic nitroalkyl anions 1d -h are less
nucleophilic than the aliphatic ones (1a -c), which may
be explained by delocalization of the negative charge into
the aromatic ring. In line with this argument, acceptor
substituents in the aromatic ring lead to a reduction of
nucleophilicity.
Figure 9 shows that the reactivities of the nitronate
anions in water also correlate poorly with σ-. The small
differences in reactivity between the differently substi-
tuted nitronates (1d -h ), which even give rise to positive
Hammett reaction constants (F), indicate that the transi-
tion states of these reactions do not reflect the partial
cancellation of conjugation between the aryl group and
the carbanionic reaction center.
The correlations with positive F values, shown in
In water, all nitronate anions are considerably less
nucleophilic than in DMSO. However, the decrease in
nucleophilicity strongly depends on the nature of the
nitronate. While the N values of the aliphatic nitronate
Figure 9, imply that the nitroalkane anomaly5 also turns
(30) Exner, O. Correlation Analysis of Chemical Data; Plenum
Press: New York, 1988.
J . Org. Chem, Vol. 69, No. 22, 2004 7571

Bug et al.
F IGURE 10. Plot of the nucleophilicity parameter N versus
pKaH of nitroalkyl anions 1a -h and keto-, ester-, and cyano-
stabilized carbanions 9a -i (water, 20 °C). For 1a -h , see Table
4 for pKaH values and Table 5 for N values. For 9a -i, pKaH
and N values are from ref 22. Points referring to uncertain
pKaH values are in parentheses.
F IGURE 8. Correlations between log k of the reactions of aryl-
substituted nitronates 1d -h with electrophiles 2c and 2e in
DMSO and the corresponding σ- values (from ref 30). Cor-
relation equations: ([) log k ) -0.97σ- + 6.16 (r2 ) 0.8319),
(2) log k ) -0.99σ- + 3.47 (r2 ) 0.9422).
To examine whether nitronate anions systematically
differ from other types of carbanions in nucleophilicity-
basicity correlations, we will now combine the kinetic
data for nitronate anions 1a -h with those for carbanions
9a -i.
Figure 10 shows that the reactivities of most carb-
anions in water correlate moderately with pKaH. Four
points deviate significantly (1a -c and 9i). The high
intrinsic reactivity of the malodinitrile anion 9i has
recently been discussed.22 We now find that aliphatic
nitronate anions 1a -c are 2 orders of magnitude less
reactive than expected on the basis of pKaH, indicating
high intrinsic barriers for the reactions of the aliphatic
nitronate anions.
F IGURE 9. Correlations between log k for the reactions of
aryl-substituted nitronates 1d -h with 2a -c in water and the
corresponding σ- values (from ref 30). Correlation equations:
([) log k ) 0.42σ- + 2.89 (r2 ) 0.6038), (2) log k ) 0.42σ-
2.32 (r2 ) 0.7424), (9) log k ) 0.41σ- + 1.37 (r2 ) 0.4786).
+
The problem of using pKaH for predicting nucleophilic
reactivities in water is most impressively demonstrated
by the comparison of the methyl nitronate 1a and the
malodinitrile anion 9i (Figure 10). Though both species
have comparable pKaH values, their nucleophilic reac-
tivities differ by a factor of 104 [9i/1a : ∆log k ) 0.54-
(19.50 - 12.06) ) 4.02].
The correlation between nucleophilic reactivities and
pKaH is considerably better in DMSO solution (Figure 11),
but even in this dipolar aprotic medium, the pKaH values
do not render a reliable prediction of nucleophilicity. One
can see, however, that in DMSO solution, nitronate ions
1a -h do not differ significantly from other types of
carbanions.
up in the reactions of aryl-substituted nitronate anions
toward carbon electrophiles in water. A detailed discus-
sion follows at the end of the next paragraph.
Cor r ela tion s betw een Nu cleop h ilicity a n d p Ka H
.
It is well-known that correlations between nucleophilic
reactivities and pKaH values only hold within narrow
classes of compounds and completely fail when nucleo-
philes with different types of central atoms are com-
pared.2 The nitroalkane anomaly5 was the most spec-
tacular example, advising against the use of pKaH for
predicting nucleophilic reactivities even in case of struc-
turally related compounds (nitronate anions).
7572 J . Org. Chem., Vol. 69, No. 22, 2004

Nucleophilicities of Nitroalkyl Anions
TABLE 6. Com p a r ison of p Ka H Va lu es in DMSO a n d
Wa ter
R
R-CH2-NO2
R-CH2-CN
pKaH in DMSO
17.2a
H
CH3
4-NO2-C6H4
31.3b
32.5b
12.3e
16.7c
8.62d
pKaH in Water
10.22f
H
CH3
4-NO2-C6H4
28.9g
30.9g
12.62i
8.60f
5.89h
a
d
From ref 17. b From ref 32. c From ref 19. From ref 21. e From
ref 33. f From ref 26. From ref 34. From ref 27. From ref 35.
g
h
i
d in Figure 12). While 1a -c in water show an increase
of nucleophilicity with increasing basicity (i.e., normal
behavior, no anomaly!), 1b is somewhat more nucleophilic
than 1a and 1c in DMSO (depending on the electrophile).
Since it is not obligatory to treat aromatic and aliphatic
nitronates separately, these examples show that the
interpretation of rate equilibrium relationships within
such small groups of compounds is highly questionable,
particularly, since the slopes of the correlations depend
on the choice of the group members.
F IGURE 11. Plot of the nucleophilicity parameter N versus
pKaH of nitroalkyl anions 1a -h and keto-, ester-, and cyano-
stabilized carbanions 9a -i (DMSO, 20 °C). For pKaH values
of 1a -h , see Table 2; for N values, see Table 5. For pKaH and
N values of 9a -i, see ref 22.
The appearance of anomalous rate equilibrium rela-
tionships in nitronate chemistry5 may be explained by
the great importance of the nitronate resonance structure
1N compared with the carbanion resonance structure 1C.
Because of the minor contribution of 1C, variation of
R1 and R2 (H, alkyl, or 4-nitrophenyl) affects pKaH in
DMSO by only 8.5 units and nucleophilicity by a factor
of approximately 103.5 (∆N ≈ 5, s ≈ 0.7). Because of this
relatively small range, other factors (e.g., steric effects
or differential solvation of ground and transition states)
become dominant. Therefore, the correlation between N
and pKaH, including all nitronates 1a -h in DMSO, is of
low quality though the slope is in the expected order.
F IGURE 12. Questionable attempts to derive relationships
between nucleophilicities and basicities of nitronate anions.
In aqueous solution, differential solvation becomes so
important that the pKaH values of nitronate anions 1a -h
differ by only 4 units and the nucleophilic reactivities
differ by a factor of less than 102 (∆N ≈ 3.5, s ≈ 0.5)
despite of the large structural variety of these nitronates.
These small differences must arise from partial compen-
sation of opposing effects, and depending on the choice
of groups of compounds, one may arrive at completely
different rate equilibrium relationships.
Let us now turn to the origin of the nitroalkane
anomaly by considering N versus pKaH correlations of
nitronates in water and in DMSO. Figure 12 shows that
it is impossible to find a reasonable single correlation for
all data in both solvents. If we follow the typical
procedure, which led to the postulate of the nitroalkane
anomaly, and look at correlations for a certain group of
compounds in a certain solvent, we might arrive at the
four correlation lines, a-d, drawn in Figure 12.
When considering the correlation lines for aromatic
nitronates 1d -h (correlations a and c in Figure 12), one
would come to the conclusion that aromatic nitronates
show an increase of nucleophilicity with increasing
basicity in DMSO but a decrease of nucleophilicity with
increasing basicity in water. We might thus corroborate
previous statements that solvation by hydrogen bonding
is responsible for the nitroalkane anomaly.5,31
Nitronates thus differ substantially from other types
of carbanions (e.g., cyano-substituted systems) because
of the insignificance of the carbanion resonance structure.
Table 6 shows that variation of R from H via CH3 to
4-nitrophenyl in DMSO affects the pKaH values of
nitronates only half as much as those of cyano-substi-
tuted carbanions. In aqueous solution, the same sub-
stituent variation reduces the basicities of nitronates by
A different conclusion might be drawn from the cor-
relation lines for aliphatic nitronates (correlations b and
(31) Keeffe, J . R.; Gronert, S.; Colvin, M. E.; Tran, N. L. J . Am.
Chem. Soc. 2003, 125, 11730-11745.
J . Org. Chem, Vol. 69, No. 22, 2004 7573

Bug et al.
TABLE 7. On e-Electr on Oxid a tion P oten tia ls (E°Ox) of Nitr oa lk yl An ion s 1a -d , F r ee En er gies of Electr on Tr a n sfer
(∆G°ET), a n d Exp er im en ta l Activa tion F r ee En er gies for th e Electr op h ile-Nu cleop h ile Com bin a tion s (DMSO, 20 °C)
E°Ox
E°Red
∆G°ET
nitronate
(DMSO)a
electrophile
(CH3CN)b
(kJ mol-1
)
∆Gq (kJ mol-1
)
1a
0.533
0.302
2f
2i
2g
2h
2i
2f
2i
2h
-1.12
-1.29
-1.13
-1.26
-1.29
-1.12
-1.29
-1.26
159.5
175.9
138.2
150.7
153.6
117.3
133.7
142.8
54.6
62.3
52.9
56.8
58.6
53.1
61.0
67.3
1b
1c
1d
0.096
0.220
a
Relative to SCE; the oxidation potentials relative to Fc/Fc+ reported in ref 19 were converted into E° values relative to SCE using the
b
+
equations E°SCE ) E°NHE - 0.241 (ref 39) and E°NHE ) E°Fc/Fc + 0.750 (ref 40). From ref 38.
SCHEME 5. Sin gle Electr on (SET) a n d P ola r
Mech a n ism in th e Rea ction of Nitr oa lk yl An ion s
w ith Electr op h iles
polar reaction will charge separation be created or
destroyed.
The free enthalpy for electron transfer can be calcu-
lated by eq 6 from the oxidation potentials of nitronate
anions 1a -h and the reduction potentials of quinone
methides 2d -i.
F IGURE 13. Effects of differential solvation on nucleophi-
licities and basicities of carbanions. Points referring to uncer-
tain pKaH values are in parentheses.
∆G°ET ) F(EOx - ERed
)
(6)
<5 units, while the corresponding cyano-substituted
carbanions differ by more than 20 units in their pKaH
values.
Figure 13 indicates that aqueous solvation reduces
nucleophilicities and basicities of carbanions proportion-
ally. This phenomenon has previously been reported by
Gilbert for SN2 reactions.36
Is Ou t er -Sp h er e E lect r on Tr a n sfer In volved ?
Since Kornblum’s pioneering investigations, it is well-
known that nucleophilic substitutions with nitronate
anions may proceed via SET processes.37 Therefore, the
question arises of whether the rate constants reported
in this paper refer to polar reactions or to SET processes
(Scheme 5). Let us analyze this situation for the reactions
of nitronate anions with the quinone methides. In the
molecule reactions, Coulomb interactions can be ne-
glected because neither in the SET process nor in the
While reduction potentials of the quinone methides
have been reported in acetonitrile solution,38 oxidation
potentials for four of the nitronate anions have been
determined in DMSO19 (Table 7). Because solvent effects
(in a comparison between acetonitrile and dichloro-
methane) on the reduction potentials of the structurally
related benzhydrylium ions 2a -c have been reported to
be small,38 we can directly connect the redox potentials
determined in CH3CN and in DMSO and calculate the
free energy of electron transfer (∆G°ET) by eq 6.
Comparison of the calculated ∆G°ET values with the
experimental activation free energies for the electro-
phile-nucleophile combinations (last column of Table 7
and Figure 14) reveals that in all cases, ∆Gq , ∆G°ET
(i.e., none of the reactions investigated in this work can
proceed via outer-sphere electron transfer).
(32) Bordwell, F. G.; Bares, J . E.; Bartmess, J . E.; Drucker, G. E.;
Gerhold, J .; McCollum, G. J .; Van Der Puy, M.; Vanier, N. R.;
Matthews, W. S. J . Org. Chem. 1977, 42, 326-332.
(33) For F. G. Bordwell’s pKa list, see http://www.chem.wisc.edu/
areas/reich/pkatable/.
Con clu sion s
Nitronates react with stabilized carbocations and
Michael acceptors as C-nucleophiles. The rate constants
for these reactions follow the linear free energy relation-
ship (eq 1), which allows us to directly compare the
(34) Richard, J . P.; Williams, G.; Gao, J . J . Am. Chem. Soc. 1999,
121, 715-726.
(35) Bernasconi, C. F.; Hibdon, S. A. J . Am. Chem. Soc. 1983, 105,
4343-4348.
(36) Gilbert, H. F. J . Am. Chem. Soc. 1980, 102, 7059-7065.
(37) Kornblum, N. Angew. Chem. 1975, 87, 797-808; Angew. Chem.,
Int. Ed. Engl. 1975, 14, 734-745.
(38) Ofial, A. R.; Ohkubo, K.; Fukuzumi, S.; Lucius, R.; Mayr, H. J .
Am. Chem. Soc. 2003, 125, 10906-10912.
7574 J . Org. Chem., Vol. 69, No. 22, 2004

Nucleophilicities of Nitroalkyl Anions
Potassium hydroxide was purchased from commercial suppli-
ers as an aqueous solution [c ) 0.1 M ( 0.1% and c ) 0.5073
M (volumetric standard)]. Water was distilled and passed
through a Milli-Q water purification system. Dimethyl sulfox-
ide (DMSO, puriss., stored over molecular sieve, H2O e 0.01%)
and acetonitrile (for HPLC, g99.9%) were used without further
purification.
Nitr o Com p ou n d s. Nitromethane (g99%), nitroethane
(g97%), and 2-nitro-propane (g96%) were purchased from a
commercial supplier and distilled before use. Compounds (1d -
g)-H were synthesized from the corresponding benzyl bromides
with NaNO2 in DMF/urea as described in the literature.44,45
4-Cyanophenylnitromethane (1h -H) was synthesized from
4-cyanotoluene with KOtBu and n-PrNO2 according to litera-
ture reports.46
Kin etics. The reactions of benzhydrylium ions with ni-
troalkyl anions were studied in aqueous solution and in
DMSO, whereas the reactions of the quinone methides with
nitroalkyl anions were only studied in DMSO. The rates of
the reactions of colored electrophiles 2a -i with nitroalkyl
anions 1a -i were measured photometrically under pseudo-
first-order conditions using a large excess of 1a -i. In aqueous
solutions, all nitroalkyl anions were generated by the treat-
ment of the corresponding acids with KOH.
F IGURE 14. Comparison of the calculated free energies
∆G°ET and the experimentally obtained ∆Gq for the reactions
of the nitroethane anion (1b) with quinone methides in DMSO.
For slow reactions (τ1/2 > 10 s), the decrease of the absor-
bances of the electrophiles was measured in a thermostated
flask with an immersion UV-vis probe using a working station
as already described.47 This involves a J &M TIDAS diode array
spectrophotometer which was controlled by Labcontrol Spec-
tacle software and connected to a Hellma 661.502-QX quartz
Suprasil immersion probe (5 mm light path) via fiber optic
cables and standard SMA connectors. The temperature of the
solutions during all of the kinetic studies was kept constant
(20 ( 0.2 °C) by using a circulating bath thermostat and a
thermocouple probe that was inserted into the reaction
mixture.
Fast reactions (τ1/2 < 10 s at 20 °C) were studied with a
stopped-flow instrument (Hi-Tech SF-61DX2 spectrophoto-
meter controlled by Hi-Tech Kinet Asyst2 software) as de-
scribed previously.8,48 The experiments were initiated by
mixing equal volumes of solutions of the nitroalkyl anion and
the electrophile. Nitroalkyl anion concentrations that were
higher than the electrophile concentrations were employed,
resulting in pseudo-first-order kinetics with an exponential
decay of the electrophile. First-order rate constants were
obtained by the least-squares fitting of the single exponential
At ) A0 exp(-k1ψ,obst) + C to the absorbance data (averaged
from at least four kinetic runs at each nucleophile concentra-
tion).
Because of the poor solubility of the benzhydrylium tet-
rafluoroborates in water, it was necessary to employ up to 1.6%
(v/v) acetonitrile as a cosolvent for the kinetic investigations
(39) Bard, A. J .; Faulkner, L. R. Electrochemical Methods: Funda-
mentals and Applications; Wiley: New York, 2001.
(40) Bordwell, F. G.; Cheng, J .-P.; J i, G.-Z.; Satish, A. V.; Zhang, X.
J . Am. Chem. Soc. 1991, 113, 9790-9795.
F IGURE 15. Comparison of the nucleophilicities of carban-
ions, n-nucleophiles, and neutral π-nucleophiles in different
solvents. (a) From ref 41. (b) From ref 8. (c) From ref 42. (d)
From ref 22. (e) From ref 11.
(41) Kempf, B.; Hampel, N.; Ofial, A. R.; Mayr, H. Chem.sEur. J .
2003, 9, 2209-2218.
(42) Bug, T.; Hartnagel, M.; Schlierf, C.; Mayr, H. Chem.sEur. J .
2003, 9, 4068-4076.
(43) Evans, S.; Nesvadba, P.; Allenbach, S. (Ciba-Geigy AG). EP
744392, 1996; Chem. Abstr. 1997, 126, 46968v.
(44) Kornblum, N.; Larson, H. O.; Blackwood, R. K.; Mooberry, D.
D.; Oliveto, E. P.; Graham, G. E. J . Am. Chem. Soc. 1956, 78, 1497-
1501.
(45) Kornblum, N.; Weaver, W. M. J . Am. Chem. Soc. 1958, 80,
4333-4337.
(46) (a) Shriner, R. L.; Parker, E. A. J . Am. Chem. Soc. 1933, 55,
766-770. (b) Boschan, R.; Merrow, R. T.; Van Dolah, R. W. Chem. Rev.
1955, 55, 485-510. (c) Fairbrother, D. M.; Skinner, H. A.; Evans, F.
W. Trans. Faraday Soc. 1957, 53, 779-783.
nucleophilic reactivities of nitronate anions with those
of other charged and noncharged nucleophiles (Figure 15;
for
a collection of nucleophilicity parameters, see
www.cup.uni-muenchen.de/oc/mayr). Because the nucleo-
philic reactivities of nitronate anions with wide structural
variety differ by a factor of less than 102 in water, they
cannot predominantly be controlled by polar substituent
effects, resulting in curious rate equilibrium relationships.
(47) Dilman, A. D.; Ioffe, S. L.; Mayr, H. J . Org. Chem. 2001, 66,
3196-3200.
(48) Mayr, H.; Ofial, A. R. Einsichten: Forschung an der LMU
Mu¨nchen 2001, 20, 30-33.
Exp er im en ta l Section
Ma ter ia ls. Benzhydrylium tetrafluoroborates8 and quinone
methides13,43 were prepared as described in the literature.
J . Org. Chem, Vol. 69, No. 22, 2004 7575

Bug et al.
in water. In previous work with other anionic nucleophiles, it
has already been shown that the small amount of acetonitrile
does not affect the observed rate constants.11
In some experiments with electrophile 2a in water, small
quantities of benzenesulfonic acid were added to avoid the
reaction of 2a with water prior to mixing the solutions of the
reactants.
We are grateful to Clemens Schlierf and Dr. Binh Phan
Thanh for experimental contributions and to Dr. Armin
R. Ofial for valuable suggestions.
Su p p or tin g In for m a tion Ava ila ble: Syntheses and char-
acterization of products 3a -g, 4a , and 5f-h and tables
containing concentrations and rate constants of the individual
kinetic experiments in DMSO and water. This material is
available free of charge via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. We thank the Alexander-von-
Humboldt Foundation for a fellowship to T.L. and the
Deutsche Forschungsgemeinschaft (Ma 673-17) and the
Fonds der Chemischen Industrie for financial support.
J O048773J
7576 J . Org. Chem., Vol. 69, No. 22, 2004