Reaction of â-Methoxy-R-nitrostilbene with Cyanamide
J . Org. Chem., Vol. 64, No. 8, 1999 2901
Ta ble 1. Su m m a r y of Ra te Con sta n ts for Nu cleop h ilic Atta ch m en t of An ion ic a n d Neu tr a l Nu cleop h iles to 1-OMe in
5
0% DMSO-50% Wa ter (v/v) a t 20 °Ca
Nu-
NuH
k
1
k
1
NuH+
Nu-
pKa
NuH
(M s-1
-1
)
NuH
Ka
2
(M s-1
)
-1
NC-NH-
b
11.38
2.7 ( 0.2
NC-NH2f
MeONH2
n-BuNH2g
b
ca. 1.1i
4.70
10.68
<2.4 × 10
7.8 × 10
1.45
-6
-2
-
c
CF3CH2O
14.0
17.33
10.56
0.73
0.69
390
-
d
H2Od
8.54 × 10-7 h
OH
HOCH2CH2S
-1.44
-
e
a
µ ) 0.5 M (KCl). b This work. Reference 4d. d Reference 12. e Reference 4a. f Reference 4e. g Reference 6. h First-order rate constant
c
divided by water concentration. i In water at 29 °C, ref 7; pKa in 50% DMSO-50% water expected to be very similar.
An important and perhaps the main factor responsible
for the higher intrinsic nucleophilicity of CNA may be
apparently greater than the expected reduction in reac-
tivity of CNA due to its resonance stabilization (eq 4).
-
-
its relatively weak solvation. An indication of weak
Such a reduction in reactivity is expected on the basis of
the generally observed phenomenon that the loss of the
resonance effect from a reactant runs ahead of bond
formation at the transition state, thereby increasing the
solvation is the rather small increase in the pK
a
of CNA
from its value in water, 10.27,21 to that in 50% DMSO-
5
1
0% water, 11.38. For CF
3
CH
2.37 in water to 14.00 in 50% DMSO-50% water and
O from 15.74 to 17.3323 for the same change in
2 a
OH the pK increases from
2
2
4d
28-30
intrinsic barrier of the reaction.
Though more reactive than the oxyanions, CNA is far
less reactive than the less basic HOCH
-
for H
solvent.
Strongly basic oxyanions and especially OH- are
known to be less nucleophilic than expected on the basis
of their pK values, a phenomenon attributed to their
strong hydrogen-bonding solvation in hydroxylic sol-
2
-
2
CH
2
S (Table 1).
This reflects the generally very high nucleophilicity of
thiolate ions.2
5,31
The exalted reactivity of thiolate ions
2
5,32
is the combined result of low solvation
and high
a
polarizability of sulfur.3
1c,33
vents.2
4-26
The reduction in reactivity is the result of the
Rea ctivity of CNA. The reaction of 1-OMe with the
requirement for partial desolvation of the nucleophile and
the fact that this desolvation runs ahead of bond forma-
neutral CNA is too slow to compete with hydrolysis, and
-
6
-1 -1
only an upper limit of 2.4 × 10
M
s
can be given
NuH
tion at the transition state, which increases the intrinsic
for k1 . The following considerations show that this
upper limit is lower than expected on the basis of
comparisons with reactions of 1-OMe with other amines.
For example, the Brønsted ânuc value calculated based
barrier27 of the reaction.
28-30
Aryloxide ions and other
weakly basic oxyanions whose solvation is weaker than
that of strongly basic alkoxide ions are considerably more
3
4
nucleophilic relative to their pK
a
. For example, in the
on the reactions of 1-OMe with CNA and n-BuNH2 is
>0.60, much higher than ânuc ) 0.25 for the reaction of
reaction of oxyanions with p-nitrothiophenyl acetate in
-
6
water, the rate constant for OH lies approximately 3.6
1-OMe with piperidine and morpholine. It is unreason-
log units below the straight line Brønsted plot defined
able that ânuc for primary amines would be so much larger
by aryloxide ions;25 in the reaction with p-nitrophenyl
than for secondary alicyclic amines; i.e., the high â
nuc
-
NuH
acetate the negative deviation for OH amounts to about
value indicates that k1
for CNA is abnormally low
3
.1 log units.25 That solvation is an important factor is
and that CNA apparently is not part of the Brønsted
also apparent when comparing our results with Bord-
well’s findings for S 2 reactions conducted in pure
family of primary amines.
One may estimate a k1
primary amine that does belong to the Brønsted family
NuH
N
value for a hypothetical
DMSO; in this medium solvation is drastically reduced
and amide ions are less reactive than oxyanions of the
NuH
with n-BuNH
2
and has a pKa
equal to that of CNA.
3
1
a
same pK .
Assuming that ânuc for this family is the same as for
secondary alicyclic amines, i.e., 0.25, one calculates a
-
The reduced solvation of CNA may, in part, be due to
delocalization of the negative charge. If this is the case,
the advantage gained from the reduced solvation is
NuH
-3
-1 -1
NuH
-1 -1
k1 ≈ 5.8 × 10
M
s
based on k1 ) 1.45 M
s
3
for n-BuNH
2
. This is 2.4 × 10 -fold larger than the upper
limit estimated for CNA. Our assumption that ânuc for
the primary amines is the same as for secondary alicyclic
amines is probably an underestimation because in reac-
tions with several other electrophilic olefins one usually
finds ânuc(1°) > ânuc(2°). For example, ânuc(1°) ) 0.22 and
(16) Schleyer, P. v. R.; J emmis, E. D.; Spitznagel, G. W. J . Am.
Chem. Soc. 1985, 107, 6393.
(
(
17) Hine, J .; Klueppl, A. W. J . Am. Chem. Soc. 1974, 96, 2924.
18) Wiberg, K. B.; Squires, R. R. J . Chem. Thermodyn. 1979, 11,
7
73.
19) Harcourt, M. P.; More O′Ferrall, R. A. J . Chem. Soc., Chem.
Commun. 1987, 823.
20) Harcourt, M. P.; More O′Ferrall, R. A. Bull. Soc. Chim. Fr. 1988,
07.
(
(
(31) (a) Bordwell, F.; Cripe, T. A.; Hughes, D. L. Adv. Chem. Ser.
1987, 215, 137. (b) Hine, J .; Weimar, R. D., J r. J . Am. Chem. Soc. 1965,
87, 3387. (c) Sander, E. G.; J encks, W. P. J . Am. Chem. Soc. 1968, 90,
6154. (d) Ritchie, C. D.; Gandler, J . J . Am. Chem. Soc. 1979, 101, 7318.
(e) Bernasconi, C. F. Tetrahedron 1989, 45, 4017. (f) Terrier, F.
Nucleophilic Aromatic Displacement; VCH Publishers: New York,
1991. (g) Bernasconi, C. F.; Ketner, R. J . J . Org. Chem. 1998, 63, 6266.
(32) (a) Parker, A. J . Chem. Rev. 1969, 69, 1. (b) Bordwell, F. G.;
Hughes, D. L. J . Org. Chem. 1982, 47, 3224. (c) Taft, R. W. Prog. Phys.
Org. Chem. 1983, 14, 247.
4
2
(
(
(
21) Kameyama, N. Trans. Am. Electrochem. 1921, 40, 131.
22) Ballinger, P.; Long, F. A. J . Am. Chem. Soc. 1960, 82, 795.
23) Hall e´ , J .-C.; Gaboriaud, R.; Schaal, R. Bull. Soc. Chim. Fr. 1970,
047.
(
(
(
24) Kresge, A. J . Chem. Soc. Rev. 1973, 2, 475.
25) Hupe, D. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 451.
26) J encks, W. P.; Brant, S. R.; Gandler, J . R.; Fendrich, G.;
Nakamura, C. J . Am. Chem. Soc. 1982, 104, 7045.
q
(
27) The intrinsic barrier, ∆G
constant k and a reverse rate constant k-1 is defined as the barrier
when K ) k /k-1 ) 1 or ∆G° ) 0.
o
, of a reaction with a forward rate
(33) (a) Pearson, R. G. Surv. Prog. Chem. 1969, 5, 1. (b) Pearson, R.
G.; Songstad, J . J . Am. Chem. Soc. 1967, 89, 1827.
1
3
5
1
1
(34) MeONH
2
is an R-effect nucleophile and hence does not belong
4e
(
(
(
28) Bernasconi, C. F. Acc. Chem. Res. 1987, 20, 301.
29) Bernasconi, C. F. Acc. Chem. Res. 1992, 25, 9.
30) Bernasconi, C. F. Adv. Phys. Org. Chem. 1992, 27, 119.
to the Brønsted family of simple primary aliphatic amines.
(35) (a) Fina, N.; Edwards, J . O. Int. J . Chem. Kinet. 1973, 5, 1. (b)
Hoz, S.; Buncel, E. Isr. J . Chem. 1985, 26, 313.