N-nitrosamide-mediated ritter-type reactions. Part II - The operation of persistent steric and π*-acceptor agostic-type effects

Article abstract of DOI:10.1039/b204255j

Benzyl cations were generated via thermolysis of N-benzyl-N-nitrosopivalamide in molten 2-R-substituted benzonitriles (R = MeO, Me, H, F, Cl, and Br). The corresponding N-2-R-benzonitrilium species, in contrast to their 4-R-benzonitrilium counterparts, underwent limited reaction with pivalate ion to form unsymmetrical diacylamines via rearrangement of their initial imidic anhydrides. The yield of diacylamines, though small, varied systematically with the nature of the R group in a manner suggesting the operation of interesting steric and/or electronic effects on the pivalate ion-nitrilium ion collapse. The ortho-substituent, though present on only one side of the benzonitrilium ion inhibits reaction at both sides via steric hindrance in the near-ground state and steric crowding in the transition state (a persistent steric effect). The proposed electronic effect involves a π*-acceptor agostic-type interaction between n or σ electrons (HOMO) and the π* system (LUMO) of the nitrilium ion. Additionally, in many cases, attack by water on the nitrilium ion occurred to a significantly larger extent than attack by the much more nucleophilic and positionally favored pivalate ion on the same species. This observation is interpreted in terms of the differences in the sizes and docking trajectories of both species with the nitrilium ion due to charge and charge distribution on both nucleophiles.

Full text of DOI:10.1039/b204255j

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N-Nitrosamide-mediated Ritter-type reactions. Part II.† The
operation of “persistent steric” and “ꢀ*-acceptor agostic-type”
effects
2
Ron W. Darbeau,* Rebecca S. Pease,‡ Edson V. Perez,§ Rebekah E. Gibble,¶ Faith A. Ayo||
and Aaron W. Sweeney||
Department of Chemistry, McNeese State University, Lake Charles, LA 70609, USA.
E-mail: rdarbeau@mail.mcneese.edu
Received (in Cambridge, UK) 2nd May 2002, Accepted 17th September 2002
First published as an Advance Article on the web 24th October 2002
Benzyl cations were generated via thermolysis of N-benzyl-N-nitrosopivalamide in molten 2-R-substituted
benzonitriles (R = MeO, Me, H, F, Cl, and Br). The corresponding N-2-R-benzonitrilium species, in contrast to their
4
-R-benzonitrilium counterparts, underwent limited reaction with pivalate ion to form unsymmetrical diacylamines
via rearrangement of their initial imidic anhydrides. The yield of diacylamines, though small, varied systematically
with the nature of the R group in a manner suggesting the operation of interesting steric and/or electronic effects on
the pivalate ion-nitrilium ion collapse. The ortho-substituent, though present on only one side of the benzonitrilium
ion inhibits reaction at both sides via steric hindrance in the near-ground state and steric crowding in the transition
state (a “persistent steric” effect). The proposed electronic effect involves a π*-acceptor agostic-type interaction
between n or σ electrons (HOMO) and the π* system (LUMO) of the nitrilium ion. Additionally, in many cases,
attack by water on the nitrilium ion occurred to a significantly larger extent than attack by the much more
nucleophilic and positionally favored pivalate ion on the same species. This observation is interpreted in terms
of the differences in the sizes and docking trajectories of both species with the nitrilium ion due to charge and
charge distribution on both nucleophiles.
1
a–c
Introduction
The N-nitrosoamide-mediated Ritter-type reaction
thermolyses of N-alkyl-N-nitrosoamides in molten nitriles.
The nitrosoamides’ decomposition generates nitrogenous-
entity separated ion-pairs (NESIPs; eqn. (1)) containing highly
reactive carbocations that are competitively scavenged by their
nascent counterion and by the solvent. The latter reaction
reversibly derives nitrilium ions
by moisture to yield amides, or by the nascent counterion to
form imidic anhydrides that isomerize into diacylamines
(DAAs) (Scheme 1). The reaction is a variation of the Ritter
reaction but differs in the source and reactivity of the carbo-
cation (deamination vs. alcohol protolysis), the primary
scavenger of the nitrilium ion (carboxylate ion vs. water) and
1
a–c
involves
1a–c
the major product (DAA vs. amide).
In a previous study,
compose in 4-R-benzonitriles (R = NH , Me N, MeO, Me,
H, F, CF ) at 60 ЊC and 90 ЊC. The yield of DAA rose
from 0% (for R = NH ) to 10.6% (R = H) then fell to 8.1%
R = CF ) (Table 2, below).
general, electron releasing groups (ERGs) enhance the nucleo-
philicity of the nitrile N facilitating capture of the benzyl
cation; however, they also later exert a yield-decreasing effect
with respect to the DAAs by diminishing the electrophilicity
of the sp-hybridized C of the nitrilium adduct. Conversely,
electron-withdrawing groups (EWGs) diminish the yield of the
nitrilium intermediate by reducing the nucleophilicity of
the nitrilic N, but subsequently make the nitrilium ion more
electrophilic. The %DAA is greatest for R = H since this group
does not abate the kinetics of either the nitrile/benzyl cation,
1a,b
nitrosoamide 1 was allowed to de-
2,3
2
2
1a–c
3
that are themselves attacked
2
1a,b
(
These data suggested that in
3
†
‡
For Part I see ref. 1a.
Currently a research associate/instructor in the Chemistry Dept,
McNeese State University.
Currently a graduate student at The University of Texas at Dallas,
Richardson, TX, USA.
Currently a graduate student at The Pharmacy School, University of
Louisiana at Monroe, LA, USA.
| Summer 2001 Louisiana Alliance for Minority Participation
LS-LAMP) Undergraduate Research Students at McNeese State
University.
§
¶
|
(
1a,b
or the nitrilium/carboxylate reactions. Although the DAAs
(
1)
2
146
J. Chem. Soc., Perkin Trans. 2, 2002, 2146–2153
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b204255j

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a
b
c
Table 1 Product distribution from the decomposition of N-benzyl-N-nitrosopivalamide in 2- and 4-tolunitrile at 60 ЊC
Relative yield
Solvent-derived products
Position
Ester
DAA
Benzyl benzamides
Benzyl alcohol
%SDP
% Benzamide of SDP
p-Me
o-Me
86.4
85.9
10.7
0.1
2.9
14.0
0.0
0.0
13.6
14.2
21.3
99.3
a
b
c
Average of at least triplicate runs. Max standard deviations: ester ≈ 0.3; DAA ≈ 0.2; Amide ≈ 0.3; alcohol ≈ 0.2. Concentration ≈ 0.045M. Data
taken from ref. 1a.
a
b
Table 2 Product distribution from the decomposition of N-benzyl-N-nitrosopivalamide in 2-R-C H CN at 60 ЊC
6
4
Relative yield
Solvent-derived products
R
Ester
DAA
Benzyl benzamides
Benzyl alcohol
% SDP
% Benzamide of SDP
Br
MeO
Cl
Me
F
H
90.6
91.5
90.2
85.9
92.8
84.5
5.3
3.6
0.2
0.1
3.2
3.1
3.0
9.1
14.0
3.6
4.9
1.0
1.0
0.5
0.0
1.0
0.0
8.4
6.6
9.3
14.2
6.8
15.1
37.0
45.5
97.8
99.3
52.9
32.5
10.6
a
b
Average of at least triplicate runs. Maximum standard deviations: ester ≈ 0.3; DAA ≈ 0.2; Amide ≈ 0.3; alcohol ≈ 0.2. Concentration ≈ 0.045M.
0
.1% when 2-methylbenzonitrile is employed as the solvent
(
Table 1). Because the polarities and other relevant bulk
physical properties of the 2- and 4-methylbenzonitriles are
likely to be very similar, the significant diminution in DAA yield
is probably derived from interactions on the molecular level.
One immediate possibility is the exertion of steric hindrance
by the 2-Me group on the approach of the pivalate ion to the
nitrilium C.
1a,b
Our hypothesis in the previous paper
was that the nucleo-
phile is obliged to attack in the plane of the aromatic nucleus
since the perpendicular p -orbital of the C–N π* orbital is
C
unavailable (or less available) because of resonance interaction
1a,c
with the aromatic nucleus (Fig. 1).
Consequently, nucleo-
Fig. 1 A simple view of the orientation of the p-orbitals in
benzonitrile showing the pathways of approach of pivalate to the
nitrilium C. Pathway “a” is favored because the p-orbital on the ipso C
is orthogonal to the plane of the aromatic sextet.
philic attack on the nitrilium ion is prone to steric hindrance by
groups, e.g., methyl, at the ortho position. Interestingly, even
though only one of the approaches to the nitrilium C is com-
pletely impeded, almost no attack from the other side occurs as
evidenced by the low yield of DAA. Since only one of two faces
is inactive, a ∼50% decrease in yield would have been expected
based solely upon statistical grounds. The virtual absence of
DAA here suggests that the methyl group may be causing more
than just steric hindrance of the approach of the nucleophile
during its attack on the nitrilium ion. The question arises as to
the nature of this additional effect that impedes nucleophilic
attack even at the sterically available site.
Scheme 1 Reaction pathways for nitrogen-separated ion-pairs in
benzonitriles.
are minor products here, they warrant study because they are
formed in highly reproducible quantities via a novel and
mechanistically interesting pathway.
An engaging problem, for example, arose with respect to
2
- vs. 4-Me-substitution in the benzonitrile. The DAA yields
from reaction of the benzyl cation in 4-methylbenzonitrile is
11%; however, the value falls abruptly by 100-fold to
∼
J. Chem. Soc., Perkin Trans. 2, 2002, 2146–2153
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The present investigation was undertaken to detail the phe-
nomenon and to elucidate the mechanism behind this severe
diminution of %DAA in the o-substituted benzonitriles.
Nitrosoamide 1 was again used as the source of the benzyl
cation in this study because of its convenient rate of decompo-
In this scenario, the same Me group exerts (1) steric hin-
drance to the approach of the nucleophile during the latter’s
reaction on the proximal face of the nitrilium ion in the near-
ground state. But, it also subsequently generates (2) steric
crowding in the transition state from nucleophilic attack on the
distal face of the nitrilium ion. We suggest that this ability of a
given group to affect a given reaction in both the near-ground
and transition states by sterically diminishing reactions at
multiple sites of the same reagent in different ways be called a
“persistent steric” or “persisteric” effect. We have not been able
to identify any other case of such an effect.
1a,b
sition
arising from steric acceleration of the rearrangement
4
step (eqn. (1)) by the tert-butyl group. 2-R-Benzonitriles (R =
F, Cl, Br, H, Me, and MeO) were used as solvents; the R-groups
were chosen to elucidate any steric and/or electronic effects
involved in the reaction.
Possible modes of deactivation of nucleophilic attack on 2-R-
benzonitrilium ions by the 2-R-substituent
An electronic argument: ꢁ
An intriguing alternative hypothesis regarding diminution in
DAA involves a type of through-space delocalization of an
ꢀ* agostic-type interactions?
The diminished yield of DAA is likely due to reduced attack by
pivalate on the nitrilium carbon ostensibly arising from some
effect [electronic (resonance, inductive, field), steric, and/or
%
appropriately oriented C–H σ electron pair over the π system
of the nitrilium ion. This effect is analogous to agostic inter-
5
orbital interactions]** exerted by the o-substituent. It can be
6a,b
actions
between C–H σ electrons and appropriate intra-
reasonably argued that the pure, classical (through-bond)
resonance effect for a given substituent in the para position
would be very similar to that in the ortho-position. To the extent
that this is true, then the diminution in the yield of the 2-
methyl- vs. the 4-methylbenzonitrile case does not arise from
differences in classical resonance effects. Similarly, induction is
unlikely to be a significant cause of the effect because it should
have little impact on the nucleophilicity of the nitrilic N (in the
nitrile) four bonds away or on the nitrilium C (in the nitrilium
ion) three bonds away. It is likely that the coupled π-system
of the aromatic nucleus and the nitrile (nitrilium) facilitates the
transmission of field effects. The impact of these effects on the
course of these reactions is also likely to be small, however,
because (1) the methyl group is very weakly polar and (2) the
field effect would enhance the electrophilicity of the nitrilium C,
but diminish the reactivity of the nitrilic N. The result, again
would be little variation in %DAA.
molecular Lewis acid transition metal centers (vide infra;
Fig. 2a). Whereas Green’s phenomenon deals with permanent
It would appear then that none of the recognized electronic
effects would be largely responsible for the observed diminution
of %DAA in the 2-Me case. Indeed, the results would then
have to be explained purely on the basis of steric and/or
orbital effects; alternatively, the intervention of another type of
electronic effect may be at work.
A steric argument: a “persistent steric” (“persisteric” effect)?
One possible explanation for the severe diminution of %DAA
in the o-tolunitrile case involves the ability of the methyl group
to sterically perturb nucleophilic attack in both the near-
ground and transition states of the nitrilium ion–pivalate ion
reaction. The near-ground state steric effect has already been
discussed in terms of hindrance to the approach of the counter-
ion on the proximal face of the nitrilium ion (obscured by the
methyl group). However, when nucleophilic attack occurs at the
face of the nitrilium ion distal to the Me group, a second steric
role may be played by the Me substituent. During such attack,
2
the sp-hybridized nitrilium C must become sp -hybridized in
the formation of the imidic anhydride. This rehybridization
requires (1) deposition of an electron pair on the nitrilium
N and the concomitant removal of the positive charge on the
latter. Additionally, (2) the linear C–N system is required to
recoil from the attacking nucleophile and lean toward the o-
substituent. The latter effect would produce significant steric
crowding in the transition state of the reaction. The result then
would be diminished nucleophilic attack even at the apparently
sterically open distal face.
Fig. 2 (a) Examples of organometallic complexes showing agostic
interactions. (b) Curved arrow representation of “bridging”
hyperconjugation between the methyl and nitrilium carbons in the
o-methylbenzonitrilium ion. (c) Molecular orbital representation of
“bridging” hyperconjugation between the methyl and nitrilium carbons
in the o-methylbenzonitrilium ion.
6a,b
σ
d interaction in stable compounds, we postulate transi-
tory σ π* interactions in metastable species in the present
case. The fact that the recipient orbital is π-type could also
classify the proposed electronic effect as “through-space
hyperconjugation” in the sense that σ electrons would be de-
localized over a π framework (Figs 2b,c). In this model, which
can be illustrated using a curved arrow perspective (Fig. 2b)
or an orbital one (Fig. 2c), electron density from the HOMO
(σ) of a suitably oriented C–H bond is donated to the LUMO
*
* The inherent difficulties of identifying, isolating, and quantifying the
complex roles that o-substituents play in dictating the course of reac-
tions at sites α to the aromatic nucleus, but attached to the ipso-carbon
5a–e
are well known.
This work does not attempt to comprehensively
rationalize this issue; indeed it is doubtful that a simple unified
approach to this problem can be found.
2
148
J. Chem. Soc., Perkin Trans. 2, 2002, 2146–2153

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(
(
π*) of the C–N bond coplanar with the aromatic skeleton
Fig. 1).
matter of an interesting and novel electronic effect that may
have significant impact on our understanding and interpret-
This ordinarily forbidden σ
π* interaction would appear
ation of physical organic phenomena.
to be encouraged by the following factors: (1) the transition
state for such an interaction is an inherently stable, planar 5-
membered ring, (2) the canonical form with the electron-
deficient benzylic entity is stabilized by resonance involving the
aromatic nucleus (Fig. 2b), (3) the low electron density and
hence high electron demand of the nitrilium carbon which
makes it an appropriate “sink”, and (4) the carbon-based
portion of the LUMO of the appropriate C–N π-bond has a
relatively swollen lobe leaning toward the o-substituent making
it capable of extending into interacting distance with the
homophasic σ orbital of the C–H bond (Fig. 2c).
To the extent that such sharing of electron density is
occurring, then the nitrilium C in the o-methylbenzonitrilium
ion is already involved in significant intramolecular bonding
and is essentially unavailable (at either lobe) for bimolecular
interaction with pivalate to form DAA. In this scenario,
the ortho- methyl group’s ability to minimize the yield of
DAA results from its exertion of (1) steric hindrance to the
approach of the nucleophile, (2) electronic compromising of
the sterically available lobe of the p-orbital (i.e. the one distal
from the o-Me), and (3) orbital effects to deactivate the
nitrilium C to nucleophilic attack [although this is related to
point (2)].
Results
Decomposition of N-benzyl-N-nitrosopivalamide (1) in
o-substituted benzonitriles
To test the veracities of the steric and electronic arguments,
nitrosoamide 1 was allowed to decompose in a variety of
other 2-R-substituted benzonitriles (R = F, Cl, Br, MeO) at
60 ЊC. The series of substituents was chosen (in lieu of say R =
n
i
t
Me, Et, Pr, Pr, Bu, etc.) because (1) both the electronic and
steric properties of the groups vary allowing the opportunity
to elucidate the potential presence of and interplay between
both candidate effects. Additionally, (2) there is a paucity
of available 2-R-substituted benzonitriles with melting points
around 60 ЊC.
1
The yields of DAA were determined by H NMR spectro-
scopy by looking specifically at the benzylic methylene protons
of the mixed diacylamines at δ 4.77 to 4.83. The data in Table 2
show that the yield of DAA
Cl < F < MeO < Br < H.
1
a,b
rises in the order (R =) Me <
Discussion
If this interpretation is true, it is noteworthy that the behavior
and effect of an o/p-methyl substituent relative to the ipso
nitrilium moiety depends upon its specific position on the
aromatic nucleus. Thus, in the para-position it behaves as an
ERG presumably involving isovalent hyperconjugation where
8
In the Taft relationship, log(k /k ) = δE , k and kH are rate
constants, and E is a steric term derived from the Van der
Waals radius of the substituent. One immediately striking
feature of this result is that the DAA yields fall as the size of
R
H
s
R
s
8,9
7b,d
the methyl H’s are protonic.
In the ortho-position, it
the ortho substituent (as measured by E ) increases (Table 3).
s
apparently exerts both a steric effect and an electronic one. In
the electronic one, however, there would be a type of umpolung
since in this position, the methyl Hs would be hydrido-type.
Additionally, the H is not shown “dislodged” from the
molecule’s framework but “bonded” to another site in the
molecule. In all likelihood the H would probably be involved
in some degree of bridging between the methyl and nitrilium
carbon atoms. Consequently, we suggest the term “hydrido-
bridging hyperconjugation” or “hybrid hyperconjugation” to
describe the phenomenon. This “through-space hypercon-
jugation” is distinct from the usual “through bond” phenom-
Since the yields of DAA are related to their rates of formation
then a given “k” term may be replaced by the corresponding
1a,b,2b
“
%DAA”.
Hence we may employ a modified Taft-type
equation as log[%DAA(R)/%DAA(H)] = δE . A plot (Fig. 3) of
s
log[%DAA(R)/%DAA(H)] vs. E of our data (Table 3) yields a
s
2
straight line with good correlation (R = 0.940) suggesting that
the relative yields of DAA and their relative rates of formation
depend directly upon the sizes of the groups in 2-R position.
The implication therefore is that a steric effect (ostensibly the
persisteric one) is operational and dominant in these Ritter-
type reactions of 2-R-benzonitriles.
7
enon. Evidently and quite reasonably, regardless of the type of
Interestingly, however, plots of the data using the modified
hyperconjugation and the dipole on the H, the result is always
the shunting of electron density to the electron-poor site in the
ion.
2
Taft equation (vide supra) are better fit (R = 0.965) to a
binomial curve. Indeed, when other steric parameters including
a 9b
9c
Meyer’s V , and Charton’s ν are employed in lieu of Es,
the double log plots are also best described by smooth curves
2
(
Figs. 4 and 5; R = 0.982 and 1.000, respectively). One inter-
Sigma
pi* agostic interactions
pretation of the nonlinearity of these plots is that there exists
another factor superimposed upon the persisteric one that
influences the course of the reaction. Additionally, from the
linearity in Fig. 3 but its absence in Figs 4 and 5, the Es
Agostic effects are through-space interactions of a C–H bond
on a ligand with low-lying d-orbitals on the metal center in a
complex. The bonding is often described as a sigma complex
of an alkane with a metal.
6
a,b
6c–e
Examples of molecules showing
agostic interactions are shown in Fig. 2a. These interactions
1
are easily detected by H NMR via (1) significant shielding of
6
d,e
the methyl Hs (typically at δ Ϫ5 to Ϫ15 ppm)
and (2) JC/H3
coupling values of ∼70–100 Hz vs. the ∼125 Hz typical of sp
hybridized carbons. Reduced C–H stretching frequencies are
6d,e
6d,e
also often observed in the IR.
Unfortunately although organometallic complexes with
agostic interactions are stable, isolable entities for which
spectroscopic evidence of the σ
obtained, the proposed interactions in the present case are
d interactions can be
6
transient. Nonetheless, to the extent that through-space σC–H
d interactions are known, the postulation of σC–H
actions have the benefit of precedence. Whether these inter-
actions are labeled “σC–H π* agostic-type”, “through-space
π* inter-
hybrid hyperconjugation” or some other appropriate name
would, in this author’s opinion, be subsidiary to the larger
Fig. 3 Plot of log[%DAA(R)/%DAA(H)] vs. E for the decomposition of
s
N-benzyl-N-nitrosopivalamide in 2-R-benzonitriles.
J. Chem. Soc., Perkin Trans. 2, 2002, 2146–2153
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a
b
Table 3 Steric effects of 2-R-substitution on the product distribution from decomposition of N-benzyl-N-nitrosopivalamide in 2-R-C H CN at
6
4
6
0 ЊC.
c
Steric parameter
2
a
b
R
Es
10 V
ν
%DAA
log[%DAA(R)/%DAA(H)]
Br
MeO
Cl
Me
F
H
—
—
0.65
—
0.55
0.52
0.27
0.00
5.3
3.6
0.2
0.1
3.2
Ϫ0.30
Ϫ0.47
Ϫ1.72
Ϫ2.03
Ϫ0.52
0.00
Ϫ0.55
Ϫ0.97
Ϫ1.24
Ϫ0.46
0.00
3.39
2.84
2.82
1.22
—
10.6
a
b
c
Average of at least triplicate runs. Maximum standard deviation: DAA ≈ 0.1; Concentration ≈ 0.045M. For values see refs 7 and 8.
Fig. 6 Curved arrow and orbital representations of n to π* through
space hyperconjugation between electron-rich 2-R substituents and the
nitrilium carbon in the 2-R-benzonitrilium ions.
as for R = Me, but also from n
that have lone pairs on the atoms attached to the ring (Fig. 6).
The ability of the heteroatom to effect n π* donation would
π* donation for substituents
appear to depend upon its size and electronegativity (although
these are not independent variables). Thus the large p-orbitals
of Br possess poor complementarity of fit (due to dissimilar
sizes and energies) with the C-based π* orbital of the C–N
bond. Thus it is the least involved in agostic interactions
resulting in an electronically unhindered nucleophilic attack at
the distal position. The presence, however, of steric hindrance
to nucleophilic attack from the face proximal to the Br as well
as some steric crowding in the transition state due to mandatory
rehybridization of the ipso carbon, serve to lower the yield
below that of R = H.
a
Fig.
4
Plot of log[%DAA(R)/%DAA(H)
]
vs. log
V
for the
decomposition of N-benzyl-N-nitrosopivalamide in 2-R-benzonitriles.
The excellent complementarity between C–O and C–F
orbital systems (C, O, and F are all mid to late second period
elements) suggests the presence of significant n
π* agostic
interactions in the R = MeO and F cases. Conversely, one would
expect relatively poor p /p fit and diminished hyperconjuga-
Cl
C
tion in the R = Cl case. If this were the major operating factor,
larger yields of DAA would have been observed in the R = Cl
case. However, O and F are extremely electronegative atoms
and are less adept at donating electron density than the larger
Cl and so the potential for n
π* donation in the R = F,
MeO cases is diminished leading to a relatively electronically
uncompromised nitrilium ion and enhanced yield of DAA in
the R = F, MeO cases relative to the R = Cl one.
Fig. 5 Plot of log[%DAA(R)/%DAA(H)] vs. log ν for the decomposition
of N-benzyl-N-nitrosopivalamide in 2-R-benzonitriles.
It would appear then that the yield of DAA in these Ritter-
type reactions is a complex function of the nature and position
of the R group on the aromatic nucleus. Although a steric
factor is operational, an electronic one made possible by π*-
acceptor agostic interactions may also be involved.
term (but not the other two) is evidently quite insensitive to the
influence of non-steric factors in the reaction (vide infra).
It is possible that this additional effect that results in the
deviations from linearity in Figs. 3–5 is indeed π*-acceptor
agostic interactions (vide supra) as proposed above for R = Me.
Although a case can be made for the forbidden stereoelectronic
9d,e
A note on steric parameters
Taft’s original E term has been shown by Charton to be a
requirements for σ
π* donation in that case, the question
arises, however, as to its origin in the other cases. One other
important question is why, even though Br is the largest group
attached to the ortho position, it allows the formation of the
second largest yield of DAA (Table 2, Fig. 5)?
s
9f
linear function of Van der Waals radii. There appears to be
universal consensus on the validity of E as a steric parameter;
9e
s
the validity of the dozen or so terms that are derivatives of Es
e
9e
We believe that the answers to both of these questions stem
(e.g., E Њ, E *, E Ј, E , etc.,) remains in question, however.
s s s s
from agostic interactions involving not only σ
π* donation
Another measure of steric effects that has been widely accepted
2
150 J. Chem. Soc., Perkin Trans. 2, 2002, 2146–2153

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is Charton’s ν term which, like E is a linear function of Van der
s
Waals radii. Indeed, E and ν are related through:
s
ν = δE ϩ C
s
and excellent correlations between the two terms have been
9j
demonstrated. It would appear from the inversion of the
shapes of the quadratic plots in Figs 4 and 5 that the δ term
is negative under these circumstances.
a
Meyer’s V values are derived from molecular mechanics
calculations and are based upon the structure of the molecule
and specifically upon the volume of the portion of the substitu-
9k
ent that is within 0.3 nm of the reaction center. Like ν and
E , it is also a function of van der Waals radii and Fig. 4 shows
s
excellent correlation amongst these various steric terms. It
would appear that a general equation of the type
a = const. (b) ϩ const.2
1
where a and b are steric terms is valid for the interrelation-
a
ships among ν, E , and V . It is noteworthy again that of the
Scheme 2 Trajectory of approach of a carboxylate ion to the nitrilium
ion in formation of an electronically and sterically strained activated
complex.
s
three terms employed in these analyses, the E term is the
least sensitive to non-steric effects operational in this reaction
s
(
vide supra).
Scheme 2 depicts the likely approach of the negatively
charged pivalate ion to the nitrilium ion. It is likely that the
early approach of the anion to the cation would be dominated
by electronic effects resulting in a reapportioning of the
charge density on the carboxylate oxygens to maximize the
electrostatic attraction between this anion and the positively
charged nitrilium N (Scheme 2). Thus strong ionic forces are
operational in defining the trajectory of approach of the
pivalate ion. At some point the lagging O (with the initially
smaller negative dipole), comes into bonding range of the
p-orbital of the nitrilium carbon and a transfer of electron
density (that is, bonding) occurs between the lagging O and the
nitrilium C.
During this phase of the reaction, the originally positively
charged N which has drawn the more negatively charged O
closely to it, becomes electron rich again and the ensuing
repulsion between the close, electron rich O and the now
electron-rich N causes both atoms to recoil away from each
other. The result is that with carboxylate attack on the nitrilium
(leading to DAA formation) the transition state experiences
significant electronic (electron rich O/N repulsion) and steric
(close nitrilium/iminyl group to 2-R substituent) inter-
actions that destabilize the activated complex and thus slow the
reaction.
Conversely, in the advance of the electrically neutral water
molecule upon the nitrilium ion, the water is probably initially
more attracted to the nitrilium N, by virtue of ion–dipole inter-
actions, but since no reasonable reaction can occur between
these two sites, the water molecule (probably while still in the
encounter complex with the nitrilium ion) may “slide” toward
the receptive nitrilium C to begin reaction. Upon such reaction
there will be no residual electron-rich particle near the
rehybridizing and polarity reversing N (vide supra) and so no
companion recoil occurs. Consequently, the transition state for
aqueous interception of the nitrilium ion experiences neither
the electrostatic nor the steric discomfort that is likely in the
pivalate case.
The relative yields of amides versus mixed diacylamines
Despite large variation of the electronic effects of the R-group
1a,b
at the 4-position of the benzonitriles, the yield of amide rela-
tive to DAA (the SDPs) changes by a relatively small amount
1
a,b
(
≈
Table 1). Thus the term (∆%amide/∆σ) for the entire range
9.††
1
a,b
In the present case, however, where the R group is
varied in the 2-position, not only are the yields of amide relative
to SDP generally much higher, but the sensitivity of the %amide
(
with respect to the SDPs only) is also greater [(∆%amide/∆σ)
≈
72; Table 2).††‡‡
It can be easily argued that the smaller water molecule is
sterically more adept than its bulkier competitor, pivalate, at
scavenging the nitrilium ion. Consequently, larger yields of
amides would be expected from this attack. The problem
with this argument, however, is that the water molecules are
present only in trace amounts in the medium (i.e., external
to the solvent cage) whereas the pivalate ion (from the first
generation benzyl cation) is present in the solvent cage with the
nitrilium ion (the second generation electrophile). Con-
sequently, pivalate ions would appear to be both positionally
and electronically favored over water to consume the nitrilium
ions.
1a,b
It has been previously argued that while still in the solvent
cage, the nitrilium and pivalate ions must undergo significant
relative motion to achieve the stereoelectronic requirement for
1b,c
the ion pair collapse to imidic anhydride. This delay before
ion pair collapse allows adventitious water molecules to enter
into bimolecular reaction with the nitrilium ion leading to
1a,b
enhanced yields of amides.
Interestingly, however, with the
para substituent the amide yields are relatively insensitive to
significant variation in the electronic nature of the R group.
1a,b
Here, however, the amide yields are generally larger and more
sensitive to the nature of R. The larger amide yields, as well as
the wider range in amide yields, can be accounted for in terms
of the docking trajectories of the nucleophiles attacking the
distal face of the nitrilium ion.
The result is that carboxylate interception of the nitrilium ion
(and hence DAA formation) is disfavored both on the proximal
face of the 2-R substituent (a steric effect) as well as on the
distal face (both an electronic and a steric effect). Here again,
steric factors apparently exert an effect on the product dis-
tribution. Note that this persisteric effect was previously
invoked to account for diminutions in DAA yield between the
ϩ
12
†
† For groups that are ERGs via resonance σ values are used; for
p
12 1,2b
those that are EWG via induction σ values are employed.
‡ σ , σ values were used here assuming that the pure electronic
effects of the substituents are similar in both the o- and p-positions.
Although this assumption is dubious at best, it is clear from the data
p
ϩ
12
‡
p p
(
Table 2 and Table 1 in ref. 1a) that the range of amide yields is larger in
the 2-R case (Table 2) over a smaller range of what organic chemists
generally understand as electron releasing to electron withdrawing
ability.
2
-R- and 4-R-benzonitriles (an “intermolecular electrophilic”
selectivity). In the present incarnation, it is being used to
J. Chem. Soc., Perkin Trans. 2, 2002, 2146–2153
2151

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account for differences in the yields of water-derived and
carboxylate-derived product (an “intermolecular nucleophilic”
selectivity).
N-Benzyl-N-nitrosopivalamide (1)
N-Benzyl-N-nitrosopivalamide was prepared from the method
described in ref. 2a; for physical data see ref. 2a.
Decomposition of N-benzyl-N-nitrosopivalamide (1) in 2-, and
Conclusion
4
-R-benzonitriles
2
-R-Benzonitriles give rise to significantly diminished yields of
In a typical run, ∼75 µl of 1 was added to 750 mg of the
appropriate nitrile in an opticlear vial. The sample was then
placed in an oven at 60 ЊC for 1h (∼ 12 half lives). The sample
was taken out of the oven and 200 µl were removed and added
to 400 µL of CDCl3 in an NMR tube and NMR spectra
were recorded. The products observed were benzyl pivalate
solvent-derived products than do their 4-R-counterparts. The
role of the 2-R-group in diminishing the formation of SDP is
evidently an intriguing marriage of steric and electronic effects
as well as orbital interactions. A novel kind of steric effect has
been suggested in which a given group sterically affects a given
reaction in both the near-ground and transition states by dimin-
ishing reactions at multiple sites of the same reagent in different
ways. The terms “persistent steric” or “persisteric” effect have
been coined to describe this apparently novel phenomenon.
(
δ 5.10), N-aryl-N-pivaloylbenzylamine (∼ δ 4.82), benzyl 2-R-
benzamides (δ 4.65), and benzyl alcohol (δ 4.56). The methyl
signals of the pivaloyl groups of the compounds in this study
are indistinguishable from each other.
The nonlinearity of Taft and related plots of log[%DAA(R)
/
%
DAA(H)] vs. appropriate steric terms (E , V and ν) based upon
s
a
Van der Waals radii suggest, however, that the effect is not
purely steric but that electronic/orbital factors may also be
operational. Interestingly, the Taft-like plot is the least sensitive
to non-steric modulation of the reaction kinetics since the data
give a good fit to a straight line.
Acknowledgements
Acknowledgement is made to the Calcasieu Parish Industrial
and Development Board Endowed Professorship administered
by the McNeese State University Foundation, the Shearman
Research Initiative administered by the Office of Research
Services, MSU, The Louisiana Alliance for Minority Participa-
tion (LS-LAMP) & The National Science Foundation (NSF)/
Louisiana Education Quality Support Fund (LEQSF), and to
the Chemistry Department, MSU for partial support of this
research. The authors also wish to acknowledge the contribu-
tions of Dr George F. Mead, Jr., Dr August Gallo (Chemistry
Department, University of Louisiana at Lafayette), Mrs Nyla
R. Darbeau, and Ms Joan E. Vallee.
A novel kind of π*-acceptor agostic-type interaction is pro-
posed in which σ
π* or n
π* donation of electron density
between the ipso atom of the 2-R-substituent (or a bond from
it) and the nitrilium C occurs. Such an interaction (a marriage
between electronic and orbital effects) in which non-π electron
density is delocalized through space over a π-system deactivates
the nitrilium species toward reaction with external nucleophiles.
The extent of this agostic effect ostensibly depends upon the
size and electronegativity of the ipso atom (and the nature of
the ipso atom–X bond).
Finally, the charge, charge distribution, and size of the nucleo-
phile attacking the nitrilium ion appear to play a significant role
in the former’s docking trajectory with respect to the nitrilium
C/N system. Consequently, both the yields and range of yields
of amide from aqueous interception of the nitrilium ion are
larger than the corresponding pivalate ion/nitrilium ion
reactions.
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without further purification. Chemical shifts in the H NMR
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