The Nature of Azo-Substituted Carbocations: N-N π-Electron Stabilization versus Nitrogen Nonbonding Electron Stabilization

Article abstract of DOI:10.1021/acs.joc.1c00140

Computational and experimental studies reveal two different modes of cation stabilization by the phenylazo group. The first mode involves a relatively weak conjugative interaction with the azo π-bond, while the second mode involves an interaction with the nitrogen nonbonding electrons. The 4-phenylazo group is slightly rate-retarding in the solvolysis of cumyl chloride and benzyl mesylate derivatives but rate-enhancing in the solvolysis of α-CF₃ benzylic analogs. The phenylazo group can become a potent electron-donating group in cations such as [Me₂C─N═N─Ph]⁺. Nonbonding electron stabilization can be strong enough to offset the very powerful γ-silyl stabilization. In aromatic cyclopropenium and tropylium cations, the demand for stabilization is quite low, and the mode of phenylazo stabilization reverts back to the less-effective π-stabilization. The solvolysis of cis-4-phenylazo benzyl mesylate is faster than that of trans-4-phenylazo benzyl mesylate. Products formed suggest a stepwise ionization, cation isomerization, and nucleophile capture mechanism. Computational studies indicate a vanishingly small barrier for the isomerization of the cis-cation intermediate to the trans-cation.

Full text of DOI:10.1021/acs.joc.1c00140

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The Nature of Azo-Substituted Carbocations: N−N π‑Electron
Stabilization versus Nitrogen Nonbonding Electron Stabilization
Xavier Creary*
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ABSTRACT: Computational and experimental studies reveal two
different modes of cation stabilization by the phenylazo group. The
first mode involves a relatively weak conjugative interaction with the azo
π-bond, while the second mode involves an interaction with the nitrogen
nonbonding electrons. The 4-phenylazo group is slightly rate-retarding in
the solvolysis of cumyl chloride and benzyl mesylate derivatives but rate-
enhancing in the solvolysis of α-CF3 benzylic analogs. The phenylazo
group can become a potent electron-donating group in cations such as
[Me2CNNPh]+. Nonbonding electron stabilization can be strong
enough to offset the very powerful γ-silyl stabilization. In aromatic
cyclopropenium and tropylium cations, the demand for stabilization is
quite low, and the mode of phenylazo stabilization reverts back to the
less-effective π-stabilization. The solvolysis of cis-4-phenylazo benzyl
mesylate is faster than that of trans-4-phenylazo benzyl mesylate. Products formed suggest a stepwise ionization, cation
isomerization, and nucleophile capture mechanism. Computational studies indicate a vanishingly small barrier for the isomerization
of the cis-cation intermediate to the trans-cation.
very large π-stabilizing conjugative interaction, the phenylazo
group in 4 has been termed a “super radical stabilizer”.6
INTRODUCTION
■
Azo compounds of general structure 1 contain one of the most
important functional groups in chemistry (Figure 1).1 Azo dyes
In view of the π-type stabilizing conjugative interaction in
radical 4, analogous interactions in carbocations are also of
interest. Cations of general structure 5, i.e, azo-substituted
carbocations, were therefore of interest. Such carbocations fall
under the general category of cations substituted with formally
electron-withdrawing groups, i.e., cations of general structure 6.
Such carbocations, as illustrated by 7−9 (Figure 2), have been
Figure 1. Compounds containing the azo functional group.
Figure 2. Carbocations with formally electron-withdrawing groups.
Received: January 18, 2021
2, despite their potential toxicity, are used in a myriad of
industries due to their range of colors.2 They also have
numerous biomedical applications, which have been recently
reviewed.3 Azo compounds such as 3 can serve as a source of
radicals and are often used as initiators in polymerization.4
Other azo compounds have found use in actinometry and in
other photochemical applications.5 Our previous interest in the
azo group was due to its radical-stabilizing properties.6 Due to a
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extensively studied in the past7,8 and can often be generated
solvolitically. In many instances, the solvolytic rates of
generation for cations 89 and 910 far exceed what would be
expected on the basis of the formal electron-withdrawing
properties of the cyano and carbonyl groups.
Scheme 2. Solvolysis of 4-Azocumyl Chloride 13
It has been suggested that certain electron-withdrawing
groups can also exert a cation-stabilizing resonance effect, as
shown by forms 10b,11 11b, and 11c12 in Figure 3. Resonance
stabilization by the cyano9 and carbonyl10 groups has also been
suggested, but the importance of carbonyl resonance stabiliza-
tion has been questioned.13
Figure 3. Resonance stabilization of carbocations with electron-
withdrawing groups.
The phenylazo group is formally electron-withdrawing, as
indicated by the Hammett σp value of +0.34.14,15 Cations of type
5 have been proposed as intermediates in the reaction of α-
chloroazo compounds 11 with Lewis acids (Scheme 1).16 These
Figure 4. M062X/6-311+G**-calculated structure of the substituted
cumyl cation 14.
Scheme 1. Generation of α-Azo Cations
involved in the stabilization of 14a. The structure of cation 14
has also been calculated in acetic acid, a commonly used solvent
in solvolysis reactions, using the polarizable continuum model
(PCM)18 available in Gaussian 16. The resultant structure 14b
(in acetic acid) is slightly different from that of cation 14a
calculated in the gas phase. The rotation of the phenylazo group
out of planarity increases to 19.2° in cation 14b (where acetic
acid is the solvent).
The isodesmic reaction shown in Scheme 3 has been used to
evaluate the stabilizing or destabilizing effect of the phenylazo
group on 14 relative to the unsubstituted cumyl cation 17. This
calculation places the stabilization of 14a at 4.6 kcal/mol in the
gas phase despite the fact that cation 14 forms less readily than
the cumyl cation 17 under solvolytic conditions. When acetic
acid is employed as the solvent in the calculation, cation 14b is
actually 1.1 kcal/mol less stable than the cumyl cation 17. This is
more in line with the experimental rate data observed in Scheme
2. Much of this reversal of cation stabilities from a vacuum to the
acetic acid solvent is due to the greater solvent stabilization of
the cumyl cation 17 relative to the solvent stabilization of the
larger phenylazo-substituted cation 14.
Benzylic Cation Studies. Attention was next focused on the
substituted benzyl cation, where the demand for cation
stabilization in this primary system should be greater than that
in the tertiary cation 14. This cation has now been generated
under solvolytic conditions from the mesylate 20 in trifluor-
oethanol, CD3CO2D, and formic acid, where simple substitution
products were observed. The rate of reaction (Table 1) was
compared to that of unsubstituted benzyl mesylate 19. The
effect of the phenylazo group (Figure 5) is a minimal rate-
cations can undergo many fascinating inter- and intramolecular
reactions. The following additional questions were also of
interest. How easily are these cations generated under solvolytic
conditions? How do they compare in terms of stability with
other cations of general type 6? What are the stabilization
mechanisms for these cations? Are they stabilized by the N−N
π-bond or the nitrogen nonbonding electrons? Reported here
are experimental and computational studies on cations 5 that
address these questions.
RESULTS AND DISCUSSION
■
Computational Studies on Cumyl Cations. The 4-
phenylazocumyl cation 14 has previously been generated
solvolytically to determine the Hammett−Brown σ+ value.15
Thus, the azo-substituted chloride 13 reacts 5.2× more slowly
than cumyl chloride in 80% aqueous acetone (Scheme 2). This
corresponds to a σ+ value of +0.17 and suggests that the
phenylazo group destabilizes the transition state, leading to the
cation 14. The structure of cation 14 has now been calculated17
at the M062X/6-311+G** level. This structure 14a (Figure 4)
shows the N−N π-bond in conjugation with both aromatic rings.
However, a careful examination of 14a shows that the N−N−
phenyl plane is rotated slightly (4.6°) out of planarity with the
cumyl cation ring. This calculated structure is in agreement with
the suggestion15 that the nonbonding nitrogen electrons are not
B
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Scheme 3. Isodesmic Reaction of Phenylazocumyl Cation 14 with Cumene
The C4−N−N angle in 23 increases to 136° and is indicative of
the increased importance of form 23b, an immonium type
cation.
Table 1. Solvolysis Rates of Various Substrates
substrate
T (°C)
solvent
k (s−1
)
19
19
19
20
20
20
26
48
48
49
49
53
58
59
60
21.5
23.0
21.5
21.5
23.0
21.5
21.5
21.5
21.5
21.5
21.5
21.5
21.5
21.5
21.5
CD3CO2D
CF3CH2OH
HCO2H
CD3CO2D
CF3CH2OH
HCO2H
CD3CO2D
CD3CO2D
CF3CH2OH
CD3CO2D
CF3CH2OH
CD3CO2D
CD3CO2D
CD3CO2D
CD3CO2D
2.98 × 10−6
2.14 × 10−4
2.66 × 10−3
1.32 × 10−6
1.57 × 10−4
1.03 × 10−3
4.84 × 10−5
3.43 × 10−5
8.63 × 10−3
4.43 × 10−6
7.13 × 10−4
7.39 × 10−3
1.48 × 10−4
2.07 × 10−7
1.66 × 10−7
The situation changes somewhat when acetic acid is
employed as a computational solvent. The phenylazo plane of
lowest energy cation 22 is now rotated 23° relative to the
benzylic cation portion of the molecule. Additionally, the 90°-
rotated cation 23 is no longer an energy minimum but instead a
transition state with one imaginary frequency. This transition
state 23 now lies only 1.8 kcal/mol above cation 22. The
potential-energy surfaces in the gas phase, as well as in acetic
acid, are therefore very flat with very small barriers to rotation.
The computational study in acetic acid suggests a single energy
minimum, while in the gas phase there are two energy minima.
What is clear is that rotation in the cation involved in the
solvolysis of mesylate 20 is a very facile process.
The behavior of the cis-phenylazo isomer 26 was also of
interest. Irradiating the trans-alcohol 24 in a number of solvents
leads (Scheme 4) to a photostationary state where the cis-
alcohol 25 predominates over the trans-alcohol 24. The actual
ratio of the two isomers depends on the initial concentration of
24, with more dilute solutions leading to a larger fraction of 25.
This mixture was converted to the corresponding mesylates in
the CH2Cl2 solvent in a standard fashion. The mesylate 26 is a
very unstable substrate that cannot be isolated in a pure form
since it decomposes upon complete solvent removal. However,
spectra of 26 can be recorded if the solvent is not completely
removed and the residue is rapidly dissolved in CDCl3.
Alternatively, cis-mesylate 26 can be prepared by the irradiation
of the trans-isomer 20 in C6D6, CDCl3, or even CD3CO2D. In
solvents such as C6D6, cis-mesylate 26 rearranges back to the
trans-isomer 20 in an autocatalytic reaction. This process can be
circumvented if a small amount of 2,6-lutidine is added before
irradiation. Under these conditions, the thermal rearrangement
of 26 back to 20 is a very slow process (half-life of 123 h) at room
temperature.
a
b
c
a
The value of 1.19 × 10−6 s−1 was used when comparing the rate of
b
20 to 26. See the Supporting Information. Extrapolated value from k
at 60.0 °C = 3.45 × 10−5 s−1 and k at 40.0 °C = 2.83 × 10−6 s−1.
c
Extrapolated value from k at 60.0 °C = 2.92 × 10−5 s−1 and k at 40.0
°C = 2.33 × 10−6 s−1.
Figure 5. Relative solvolysis rates of benzylic systems.
When dissolved in CD3CO2D, mesylate 26 reacts readily at
room temperature to give a major product of the internal return,
the less reactive trans-mesylate 20. Also formed are the trans-
acetate 27 and a smaller amount of the cis-acetate 28 (Scheme
5). Mesylate 26 is 41× more reactive than the trans-isomer 20 in
CD3CO2D. These observations are in line with a mechanism
where the ionization of 26 is followed by the facile internal
return of the mesylate anion to form mesylate 20. It is tempting
to suggest that ionization initially leads to the cis-cation 29,
which can capture the solvent to give cis-acetate 28 or readily
isomerize to the trans-cation 22, which leads to 20 and 27.
Computational studies were used in an attempt to evaluate the
properties of cis-cation 29. While the observation of a small
amount of the cis-acetate 28 does implicate cis-cation 29 as a very
transient intermediate, computational studies failed to locate
retarding factor that ranges from 1.35 to 2.56 compared to the
unsubstituted benzyl mesylate 19. This contrasts with the
phenylazo effect in the corresponding cumyl system, 13, where
the phenylazo group retards the rate by a somewhat larger factor
of 5.2.
M062X/6-311+G** computational studies (Figure 6) have
located the planar cation 22 as an energy minimum. This cation
is delocalized as in form 22b (nitrenium ion -type stabilization).
A second structure, the 90° rotated cation 23, has also been
located, and this structure is not a transition state but instead a
separate energy minimum in the gas phase. This cation state lies
only 2.3 kcal/mol above the planar cation 22. The computa-
tional study suggests the increased importance of cation
stabilization by the nitrogen nonbonding electrons relative to
the N−N π-electrons as the amount of charge on C4 increases.
C
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Figure 6. M062X/6-311+G**-calculated structures of benzylic cations 22 and 23.
barrier is further reduced to 13.4 kcal/mol. The values for the
methoxy-substituted cation 33 and the α-CH3 benzylic cation
34 drop to 8.1 and 1.3 kcal/mol, respectively, suggesting that the
inversion of cations 32−34 should occur rapidly at room
temperature. The reason for this decrease in the inversion
barrier has been suggested19 to involve the increased importance
of forms such as 38a (Figure 8) in the transition state. In other
words, as C4 of the substituted phenyl group becomes more
electron deficient, the interaction with the nitrogen nonbonding
electrons increases. cis-Cations that are less stable than 34 (e.g.,
the cation 29) could not be located as energy minima.
Computationally, they revert to the trans-cations. On the basis
of this systematic lowering of the isomerization barrier as the C4
carbon becomes more electron deficient, it is not surprising that
benzylic cation 29 cannot be located as an energy minimum.
This computational study suggests that there is no barrier for the
conversion of 29 to the trans-isomer 22.
Scheme 4. Preparation of Mesylate 26
α-Trifluoromethyl Benzyl Cations. Can the phenylazo
group become stabilizing in a benzylic-type cation? Can nitrogen
nonbonding electron stabilization surpass N−N π-stabilization
in such cations? In an attempt to induce such behavior, the
demand for cation stabilization was further increased by the
inclusion of the trifluoromethyl group into the benzylic cation.
Thus, the ketone 46 was prepared (Scheme 6) by the
trifluoroacetylation of the organolithium reagent derived from
the iodide 45.21 The borohydride reduction of ketone 46 gave
the alcohol 47, which in turn was converted to the desired triflate
48.
The rate of reaction of triflate 48 in CD3CO2D, where the
corresponding acetate product was formed, was examined
(Table 1). Triflate 48 was found to be 7.8× more reactive than
the corresponding unsubstituted triflate 49 (Figure 9). In
trifluoroethanol, this increased reactivity of 48 was a factor of
12.1. This is consistent with stabilization of the cationic
intermediate by the phenylazo group. This contrasts with the
behaviors in the substituted cumyl chloride 13 and the benzylic
mesylate 20, where the phenylazo effect is rate retarding. While
this cation-stabilizing rate effect is interesting, it does not allow
this cation as an energy minimum. All attempts to locate 29
resulted in a conversion to the trans-cation 22.
Previous computational studies have been carried out on cis-
azobenzene, 30, and its substituted analogs in addition to the
barrier to conversion to the more stable trans-analogs.19 The
conversion of the cis-azo compounds to their trans-analogs can
occur by two reasonable mechanisms.20 The first involves a
rotation about the π-bond of the azo group. Such a transition
state should have a biradical or dipolar character. A second
possibility involves inversion at the sp2-hybridized nitrogen
center. It has been found that this inversion barrier decreases as
the substituents on one of the phenyl groups become more
electron-withdrawing. Our current M062X/6-311+G** calcu-
lations (Figure 7), which utilize acetic acid as a solvent, confirm
this previous study,19 which was carried out at the B3LYP/6-
31G* level. The transition state for the conversion of the cis-
azobenzene, 30, to the trans-azobenzene, 36, lies 29.0 kcal/mol
above that of 30. This value drops to 23.6 kcal/mol in the
aldehyde 31. What are the inversion barriers in cationic systems?
In the stabilized benzylic cation 32 (a protonated imine), the
D
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Scheme 5. Reaction of Mesylate 26 in CD3CO2D
Figure 8. M062X/6-311+G**-calculated structures of the cis-azo
cation 33 and the transition state 38.
Scheme 6. Preparation of Triflate 48
Figure 7. M062X/6-311+G**-calculated barriers in HOAc for
inversion in cis-azobenzenes.
one to decide on the mode of the azo stabilization of the cationic
intermediate.
A computational study was carried out on α-CF3-substituted
cations 50 and 51, where the CF3 group should increase the
charge delocalization to C4. Both cations are energy minima in
the gas phase and acetic acid. Scheme 7 shows that cation 50 and
the rotated cation 51 differ by only 0.6 kcal/mol in the gas phase.
In an acetic acid solvent, cation 50 is not completely planar.
Instead, the phenylazo plane is rotated 14° relative to the other
aryl ring. The rotated cation 51 in acetic acid is actually 1.0 kcal/
mol lower in energy than 50. The cation 50, which is stabilized
by the N−N π-bond (nitrenium ion-type stabilization), and the
rotated cation cation 51 (immonium ion-type stabilization) are
therefore of comparable energies. Of interest is the C−N−N
bond angle in 51 that increased to 152° (162° in HOAc), which
is indicative of the increased interaction of the nitrogen
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8). However, the disappearance of 53 is not strictly first order,
i.e., the apparent first-order rate constant decreases as the
reaction progresses (Figure S23). This is indicative of a common
ion rate suppression. Indeed, when 0.1 M tetramethylammo-
nium chloride is added at the beginning of the reaction, the rate
of the reaction is greatly suppressed. When no buffering base is
added to the CD3CO2D, 53 does not react completely. The
reaction reaches an equilibrium position containing both 53 and
the acetate 55 in amounts that depend on the starting
concentration of 53. This behavior provides classic evidence
for the involvement of a relatively stable cationic intermediate
54 that lives long enough in the solution to reach the dissociated
ion-pair stage. Externally added chloride ion can trap the
intermediate 54 and thereby return it to the starting chloride 53.
The reaction of 53 in CD3OD containing 0.0646 M sodium
azide at room temperature (Scheme 8) supports the suggestion
of a relatively stable cationic intermediate 54. Jencks and
Richard have used this method to estimate carbocation lifetimes
in solution.22,23b Under these conditions, the azide 56 was the
predominant product formed (88%), while only 12% of the
solvent capture product 57 was formed. Apparently, methanol
reacts with cation 54 rather slowly (relative to the azide ion).
Since this product ratio (88:12) should equal the ratio of
Figure 9. Relative solvolysis rates of α-CF3-substituted benzylic
systems.
nonbonding electrons with the electron-deficient C4. The
structure 51 becomes more “allene like” as the nitrogen becomes
more sp hybrid in character. The transition state 52 for the
interconversion of these isomers has been located and is only 1.3
kcal/mol above 50 (0.7 kcal/mol in HOAc). The potential-
energy surface is therefore quite flat and indicative of the facile
interconversion of 50 and 51. It is therefore quite probable that
both cations are involved in the solvolysis of triflate 48.
The 2-(Phenylazo)propyl Cation. Attention was next
focused on the cations of general structure 12, where the
phenylazo group is attached directly to the cationic center. The
cation 54 was previously generated under Lewis acid conditions
and can effectively alkylate toluene.16a This cation has now been
generated from the chloride 53 under solvolytic conditions in a
variety of solvents. The behavior of 53 in CD3CO2D is quite
revealing. When buffered with 2,6-lutidine, 53 rapidly forms the
acetate substitution product 55 in CD3CO2D in a reaction that is
essentially complete after 30 min at room temperature (Scheme
k
azide[NaN3]/kCD3OD, these data allow one to calculate the value
of kazide/kCD3OD. This value of kazide/kCD3OD is 114 M−1. Since
k
azide is close to the diffusion-controlled limit23 of 5 × 109 M−1
s−1, kCD3OD is significantly smaller than the diffusion controlled
limit. In other words, cation 54 has an appreciable lifetime in
pure CD3OD. By way of contrast, the kazide/kCH3OH value is 0.67
M−1 for the solvolysis of cumyl chloride 58 under the same
conditions. This suggests that the 3° benzylic cumyl cation 17 is
much shorter lived than cation 54.
Scheme 7. M062X/6-311+G**-Calculated Interconversion of Cations 50 and 51 via Transition State 52
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Scheme 8. Reactions of Chloride 53 in CD3CO2D and CD3OD with Added NaN3
Figure 10. Relative solvolysis rates of 53 and its substituted analogs.
Scheme 9. M062X/6-311+G**-Calculated Isodesmic Reaction of Cation 54 with Isobutane
Figure 11. M062X/6-311+G**-calculated structures of cation 54 and transition state 64.
How does the rate of solvolysis of chloride 53 compare with
those of other chlorides? For comparison purposes, rate data
were obtained for the chlorides 58−60 (Table 1) and are
summarized in Figure 10. Because of the common ion rate
suppression during the acetolysis of 53, the rate given in Table 1
represents an initial rate. This initial rate was determined by
rapidly mixing CD3CO2D (containing buffering 2,6-lutidine)
with 53 and then rapidly quenching portions of this solution in
rate when attached directly to a developing cationic center. The
acetolysis rate of 53 is 44 500× faster than that of t-butyl
chloride, 60, and also exceeds that of cumyl chloride, 58. These
data suggest that the cation-stabilizing ability of the phenylazo
group greatly exceeds those of the methyl group and the phenyl
group. Of interest is the observation that the phenylazo group of
53 is substantially more cation-stabilizing than the oxime
functional group in 59 (a group that is cation-stabilizing via a π-
conjugative effect).12 These relative rate comparisons also lead
to the conclusion that the cationic intermediate 54, derived from
acetolysis of 53, is highly stabilized.
1
C6D6 prior to H NMR analysis. The rate constant in Table 1
represents a value determined from the first 20 seconds of the
reaction (Figure S25). A comparison of the rate of 53 with these
substrates shows that the phenylazo group greatly enhances the
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Computational studies (M062X/6-311+G**) were used to
further sort out the structure and energetics of cation 53. The
isodesmic reaction shown in Scheme 9 allows a comparison with
t-butyl cation 63, i.e., a comparison of the cation-stabilizing
ability of the methyl group vs the phenylazo group. This
calculation suggests that 54 is significantly stabilized relative to
the t-butyl cation, but the calculation is quite solvent dependent.
The stabilization energy of 24 kcal/mol in the gas phase drops to
13.3 kcal/mol when acetic acid (used for the solvolytic studies in
Figure 10) is included as the solvent when using the polarizable
continuum model.
Scheme 10. Preparation of Chlorides 67 and 68
As is expected based on the previously calculated structure of
54,24 as well as a dialkyl-α-phenylazo cation,16a our calculated
structure of cation 54 shown in Figure 11 indicates that
stabilization is due to the nitrogen nonbonding electrons. In
valence-bond terms, the C−N−N bond angle of 170° (172° in
acetic acid) is in line with the central nitrogen being essentially
sp hybridized due to the extensive interaction of the nitrogen
nonbonding electrons with the cation vacant orbital. The planar
form 64 is not an energy minimum but instead a transition state
(one imaginary frequency) lying 12.4 kcal/mol (14.7 kcal/mol
in acetic acid) above 54. These calculations imply that as the
charge increases at the cationic center, the nitrogen nonbonding
electron pair becomes a more effective cation stabilizer.
Computationally, how does the azo group compare with other
cation stabilizers and destabilizers? Figure 12 shows M062X/6-
comparable rates in CD3CO2D. However, as in the case of
chloride 53, there was a common ion rate suppression during
acetolysis, which complicated the determination of first-order
rate constants. The formation of the product mixtures 71 and 72
is indicative of the involvement of a classical cationic
intermediate 69, which is not stabilized by the γ-trimethylsilyl
group. This cation can capture the solvent from the bottom as
well as from the top. The nonclassical bicyclobutonium-type
cation 70 is not involved. If such a cation, 70, were involved,
then the expected products would be exclusively the acetate 71a
or the methyl ether 71b. This is based on our previous studies25
that show that nonclassical 3-trimethylsilylcyclobutyl cations 73,
which contain a wide variety of R groups ranging from H, to CH3
to Ar, all capture the solvent exclusively from the bottom side to
give only products 74.
Computational studies are in line with the conclusion that
cation 69 is a classical cation that does not involve γ-
trimethylsilyl stabilization. Figure 13 shows the calculated
structure of cation 69. The cross-ring C1−C3 bond distance is
2.095 Å, which indicates no significant cross-ring interaction
with the rear lobe of the C3−Si bond. The C3−Si bond length is
1.910 Å, which is expected for a “normal” carbon−silicon bond.
The stabilization of 69 is of the “immonium” type as in structure
69a, which is evidenced by the 169 °CNN angle. This type of
stabilization in 69a is apparently enough to offset potential
bicyclobutonium-like stabilization as well as the cross-ring γ-
trimethylsilyl stabilization shown in 70.
Further Computational Studies. Do α-phenylazo-sub-
stituted carbocations ever exist preferentially in the planar (π-
stabilized) form? M062X/6-311+G** computational studies
were carried out to provide further insight. The formally
aromatic cations 75−77 (Figure 14) were examined, since these
highly stabilized cations should have a reduced demand for
phenylazo stabilization. Indeed, cations 75a and 76a are planar
energy minima in the gas phase. The conformations of 75a and
76a, with the azo group rotated 90° from the plane of the
aromatic cation rings, are transition states lying only 2.5 and 4.5
kcal/mol above 75a and 76a, respectively. The phenylazo group
in cation 77a is slightly twisted out of planarity by 22° with the
cycloheptatrienyl ring. The perpendicular conformation of 78 is
a transition state 4.2 kcal/mol above 77a. These studies show
that the N−N π-bond of the phenylazo group will indeed align in
conjugation with a cationic center as long as the demand for
cation stabilization is not too large. The situation was slightly
different when the calculation was carried out in acetic acid.
Cation 76b is no longer planar, but the aromatic pyranyl portion
of the cation is slightly twisted (16°) out of conjugation with the
phenylazo group. Further twisting was also observed for cation
77b, which was rotated by 29° in acetic acid.
Figure 12. M062X/6-311+G**-calculated relative stabilization en-
ergies of cations 65 (kcal/mol).
311+G**-calculated stabilization energies of cations relative to
the t-butyl cation (R = CH3) using isodesmic reactions
analogous to Scheme 9. Phenylazo stabilization, when directly
attached to the cationic center of 65, exceeds those of the O-
methyl oxime group and the phenyl group. These computational
studies are in line with the rate data in Figure 9, where the rate
data parallel the calculated cation stabilization energies.
γ-Silyl Substitution. Given the extraordinary cation-
stabilizing properties of the phenylazo group directly attached
to a carbocationic center, it was of interest to determine if this
group could offset the stabilization of other potent cation
stabilizers. Our studies,25 and those of others,26 have shown that
the γ-trimethylsilyl group can be a potent cation-stabilizing
group. The γ-trimethylsilyl cation 69 (or 70) was therefore
chosen for study. Is this cation stabilized by the γ-trimethylsilyl
group or has this remote stabilization been “wiped out” by the
phenylazo group? What is the geometry of the phenylazo group
with respect to the R2C+ plane (perpendicular as in 54 or planar
as in 64)? The azo compounds 67 and 68 were therefore
prepared (Scheme 10) as a mixture of isomers by the oxidation
of the hydrazone 66.
The reaction of this mixture of chlorides 67 and 68 at room
temperature in CH3CO2H gave the acetates 71a and 72a as a
69:31 mixture of isomers (Scheme 11). In CH3OH, ethers 71b
and 72b were formed in a 73:27 ratio. Both 67 and 68 reacted at
H
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Scheme 11. Reaction of Chlorides 67 and 68 in CH3CO2H and CH3OH
Figure 13. M062X/6-311+G**-calculated structure of cation 69.
The methoxy group in cation 79 is also stabilizing enough that
the planar form of the cation is the lowest-energy conformation
(Figure 15). A second energy minimum, cation 80, could be
located where the phenylazo group is rotated 28° (32° in
HOAc) out of conjugation with the cationic center. This
conformation of 80 is in line with stabilizing interactions with
both the nitrogen nonbonding electrons and the N−N π-bond
(since neither of these orbitals are orthogonal to the vacant p-
orbital at the cationic center). Unlike the methoxy group, the
phenyl group does not offer sufficient stabilization in cation 81,
and this planar conformation is no longer the lowest energy. The
rotated allene-like conformation 82 now becomes the lowest-
energy minimum in both the gas phase and the acetic acid
solvent.
manifests when the phenylazo group is in the para-position of
cumyl and benzylic cations 14 and 22, respectively. Based on the
experimental rates of formation of cations 14 and 22, the
phenylazo group behaves as a net electron-withdrawing group.
This N−N π-stabilization is therefore a weak stabilizing effect
that barely offsets the inductive effect of the azo group. The
second stabilization mode involves the interaction of a carbon
with the adjacent nitrogen nonbonding electrons and imparts an
immonium ion character to the adjacent nitrogen. This
stabilization mode becomes competitive with the π-stabilization
mode in the α-CF3-substituted benzylic cations 50 and 51,
where the demand for stabilization is increased. Experimentally,
cations 50 and 51 are formed more readily than the
unsubstituted cation [PhCHCF3]+, indicating that the phenyl-
azo group is now a weak electron-donor group. The phenylazo
group becomes a potent electron-donor group in cation 54
[Me2CNNPh]+, where stabilization involves the nitro-
gen nonbonding electrons. The cation 54 is relatively stable and
lives long enough in a methanol solution to be effectively
trapped by externally added azide ion. Thus, with the increased
demand, nitrogen nonbonding electron stabilization is more
potent than N−N π-stabilization and is even strong enough to
CONCLUSIONS
■
Computational studies show that there are two different modes
by which the phenylazo group can stabilize an electron-deficient
carbon center. The first mode involves an interaction with the
N−N π-bond. This involves charge delocalization from the
carbon to the second nitrogen atom, which imparts a nitrenium
ion character to this nitrogen. This type of delocalization
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EXPERIMENTAL SECTION
■
General. NMR spectra were recorded on a Varian DirectDrive 600
MHz spectrometer. HRMS measurements were carried out using a
Bruker MicroTOF-II spectrometer (electrospray ionization source with
time-of-flight mass analyzer).
Preparation of trans-4-Phenylazobenzyl Mesylate (20). To 4-
phenylazobenzyl alcohol27 (67.4 mg, 0.318 mmol) partially dissolved in
3 mL of CH2Cl2 was added 48.3 mg (0.422 mmol) of mesyl chloride.
The solution was cooled in an ice/salt bath at −10 °C, and 53.8 mg
(0.533 mmol) of Et3N in about 1.0 mL of CH2Cl2 was added dropwise.
The mixture was warmed to room temperature and then taken up into 5
mL of ether. Then, 3 mL of pentane was added. The solution was
consecutively washed with cold water, a cold dilute HCl solution, cold
water, a NaHCO3 solution, and a saturated NaCl solution and then
dried over a mixture of Na2SO4 and MgSO4. After filtration, the solvent
was removed using a rotary evaporator to give 88.3 mg (96% yield) of
the mesylate as an orange solid, mp >95 °C (dec). The mesylate
discolors upon standing at room temp. It was stored in an ether solution
at −20 °C. Mesylate 20 gave no parent peak during the attempted
HRMS analysis. 1H NMR of 20 (600 MHz, CDCl3): δ 7.98−7.91 (m, 4
H), 7.58 (d, J = 8.5 Hz, 2 H), 7.56−7.48 (m, 3 H), 5.32 (s, 2 H), 2.97 (s,
3 H). 13C{1H} NMR of 20 (150 MHz, CDCl3): δ 153.0, 152.5, 135.9,
131.4, 129.5, 129.2, 123.3, 123.0, 70.7, 38.5.
Preparation of cis-4-Phenylazobenzyl Alcohol (25). trans-4-
Phenylazobenzyl alcohol, 24 (27 mg), was dissolved in 7 mL of C6H6.
The solution was irradiated in a Rayonet Photochemical Reactor using
350 nm bulbs for 100 min. The C6H6 was removed at approximately a
30 mm pressure using a water aspirator. NMR analysis showed a
mixture containing 85% cis-4-phenylazobenzyl alcohol, 25, and 15%
trans-4-phenylazobenzyl alcohol, 24. 1H NMR of 25 (600 MHz,
CDCl3): δ 7.15 (t, J = 7.3 Hz, 4 H), 7.05 (t, J = 7.3 Hz, 1 H), 6.73 (d, J =
8.3 Hz, 4 H), 4.53 (s, 2 H). 13C{1H} NMR of 25 (150 MHz, CDCl3): δ
153.4, 152.5, 140.2, 128.8, 127.2, 120.9, 120.4, 64.6. HRMS (ESI): m/z
(M + H)+ calculated for C13H13N2O 213.1022, found 213.1024.
Preparation of cis-4-Phenylazobenzyl Mesylate (26). A
mixture of 22 mg of the alcohols 24 and 25 (0.104 mmol; 70% cis-
alcohol 25) in 2 mL of CH2Cl2 was cooled to −10 °C, and 30 mg of
CH3SO2Cl (0.262 mmol) in 0.2 mL of CH2Cl2 was added. Then, a
solution of 40 mg of Et3N (0.396 mmol) in 0.2 mL of CH2Cl2 was
added dropwise. The mixture was warmed to about 10 °C and then
transferred to a separatory funnel. Pentane (8 mL) was then added, and
the mixture was extracted with cold water, a cold dilute HCl solution,
cold water, a NaHCO3 solution, and a saturated NaCl solution. After
drying over a mixture of Na2SO4 and MgSO4, the solution was stored at
−20 °C. Mesylate 26 readily decomposed upon complete solvent
Figure 14. M062X/6-311+G**-calculated structures of cations 74−77
and transition state 77.
offset potential γ-silyl stabilization in the cation 69. However, in
the aromatic cations 75−77, the demand for cation stabilization
is quite low. Hence, stabilization reverts back to the less effective
N−N π-stabilization.
The unusual cis-phenylazo mesylate 26 reacts much faster
than the trans-mesylate 20 under solvolytic conditions. The
products formed in acetic acid-d4 are mostly rearranged to trans-
isomers. They are in line with a stepwise ionization, cation
isomerization, and nucleophile capture mechanism for cis-
mesylate 26. Computational studies suggest, however, that no
barrier exists for the isomerization of the cis-phenylazo cation 29
to the trans-phenylazo cation 22.
Figure 15. M062X/6-311+G**-calculated structures of cations 79−82.
J
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removal. The solvent was partially removed from a solution of mesylate
26 in CH2Cl2/pentane using a rotary evaporator and cooling in ice. The
residue was rapidly dissolved in CDCl3, and spectra were recorded at 0
°C. Even at this temperature, cis-mesylate 26 rearranged to trans-
mesylate 20.
(600 MHz, CDCl3): δ 7.97−7.91 (m, 4 H), 7.64 (d, J = 8.5 Hz, 2 H),
7.56−7.48 (m, 3 H), 5.12 (m, 1 H), 2.74 (d, J = 4.2 Hz, 1 H). 13C{1H}
NMR of 47 (150 MHz, CDCl3): δ 153.2, 152.6, 136.3, 131.4, 129.2,
128.3, 124.0 (q, 1JCF = 282 Hz), 123.00, 122.96, 72.5 (q, 2JCF = 32 Hz).
HRMS (ESI): m/z (M + H)+ calculated for C14H12F3N2O 281.0896,
found 281.0893.
Alternatively, cis-mesylate 26 can be prepared in a CDCl3 solution by
the irradiation of trans-mesylate 20 in the presence of 2,6-lutidine.
Thus, a solution of 3.2 mg of mesylate 20 in 4 mL of CDCl3 containing
approximately 1.5 mg of 2,6-lutidine was irradiated for 10 min in a
Rayonet Photochemical Reactor using 350 nm bulbs. The volume was
then reduced to about 1 mL using a rotary evaporator, and NMR
spectra showed mesylates 26 and 20 in a 75:25 ratio. Mesylate 26 gave
no parent peak during the attempted HRMS analysis. 1H NMR of 26
(600 MHz, CDCl3): δ 7.31 (d, J = 8.2 Hz, 2 H), 7.25 (t, J = 7.6 Hz, 2 H),
7.16 (t, J = 7.5 Hz, 1 H), 6.87 (d, J = 8.2 Hz, 2 H), 6.83 (d, J = 8.2 Hz, 2
H), 5.17 (s, 2 H), 2.89 (s, 3 H). 13C{1H} NMR of 47 (150 MHz,
CDCl3): δ 154.1, 153.2, 132.3, 129.3, 128.8, 127.7, 120.9, 120.5, 70.6,
38.4.
Preparation of Triflate 48. A solution of 63 mg (0.225 mmol) of
alcohol 47 in 1.0 mL of CH2Cl2 was stirred, and 54 mg (0.505 mmol) of
2,6-lutidine in 1.0 mL of CH2Cl2 was added. The mixture was cooled to
−10 °C, and a solution of 122 mg of triflic anhydride (0.433 mmol) in
0.6 mL of CH2Cl2 was then added dropwise at −10 °C. The mixture
was warmed to 0 °C and then transferred to a separatory funnel using 3
mL of ether. Pentane (6 mL) was then added, and the mixture was
rapidly extracted with cold water, a dilute HCL solution, cold water, a
NaHCO3 solution, and a saturated NaCl solution. The organic extract
was dried over a mixture of Na2SO4 and MgSO4 and filtered, and
solvents were removed using a rotary evaporator to give 82 mg (88%
yield) of triflate 48 as an orange solid that decomposed when heated
above 80 °C. Triflate 48 was stored in an ether solution at −20 °C.
Triflate 48 gave no parent peak during the attempted HRMS analysis.
1H NMR of 48 (600 MHz, CDCl3): δ 8.01 (d, J = 8.5 Hz, 2 H), 7.97−
7.92 (m, 2 H), 7.66 (d, J = 8.3 Hz, 2 H), 7.57−7.51 (m, 3 H), 5.93 (q, J =
5.8 Hz, 1 H). 13C{1H} NMR of 48 (150 MHz, CDCl3): δ 154.3, 152.4,
131.9, 129.9, 129.2, 129.0, 123.5, 123.2, 121.4 (q, 1JCF = 280 Hz), 118.3
(q, 1JCF = 320 Hz), 82.1 (q, 2JCF = 36 Hz).
cis-Mesylate 26 can also be prepared in CD3CO2D in situ by the
irradiation of trans-mesylate 20. Thus, a solution of 1.0 mg of
CD3CO2Na in 1.028 g of CD3CO2D was added to 1.0 mg of mesylate
20. A portion of this solution was irradiated in a 3 mm NMR tube for 6
1
min. Immediate H NMR analysis showed mesylates 26 and 20 in a
75:25 ratio. 1H NMR of 26 (600 MHz, CD3CO2D): δ 7.37 (d, J = 8.32
Hz, 2 H), 7.28 (t, J = 7.6 Hz, 2 H), 7.19 (t, J = 7.5 Hz, 2 H), 6.94 (d, J =
8.3 Hz, 2 H), 6.89 (d, J = 8.0 Hz, 2 H), 5.18 (s, 2 H), 2.96 (s, 3 H). This
solution was immediately used for a kinetic study.
Preparation of Chloride 53. This substrate was prepared as
previously described.16a
Preparation of Ketone 46. Using the previously described
procedure for the preparation of 4-lithioazobenzene,28 4-iodoazoben-
zene, 4529 (604 mg, 1.960 mmol) was dissolved in 35 mL of ether under
nitrogen, and the stirred mixture was cooled to −78 °C. Some of the
iodide 45 comes out of solution at this temperature. n-Butyllithium (1.4
mL of 1.6 M in hexanes, 2.240 mmol) was added dropwise via syringe.
The mixture was stirred at −78 °C for 3 h and then slowly warmed to
−30 °C. The mixture was cooled to −78 °C, and a solution of 420 mg of
ethyl trifluoroacetate (2.956 mmol) in 7 mL of ether was slowly added
dropwise. The mixture was stirred for 1 h at −78 °C and then slowly
warmed to −20 °C. The reaction was then quenched with water. After
the ice melted, the mixture was transferred to a separatory funnel. The
ether phase was washed with water and a saturated NaCl solution and
then dried over a mixture of Na2SO4 and MgSO4. After filtration, about
3 g of silica gel was added to the ether solution, and the solvent was
removed using a rotary evaporator. The dry powder was then added to a
column prepared from 10 g of silica gel packed with 1% ether in
pentane. The column was eluted with increasing amounts of ether in
pentane. The ketone 46 eluted with 4−6% ether in pentane. Solvent
removal gave 180 mg (33% yield) of ketone 46 as a red-orange solid, mp
77−78 °C. 1H NMR of 46 (600 MHz, CDCl3): δ 8.25 (d, J = 8.7 Hz, 2
H), 8.04 (d, J = 8.7 Hz, 2 H), 8.01−7.96 (m, 2 H), 7.59−7.53 (m, 3 H).
13C{1H} NMR of 46 (150 MHz, CDCl3): δ 180.0 (q, 2JCF = 36 Hz),
156.2, 152.5, 132.4, 131.4 (q, 3JCF = 2.4 Hz), 131.0, 129.3, 123.4, 123.3,
116.7 (q, 1JCF = 191 Hz). HRMS (ESI): m/z (M + H)+ calculated for
C14H10F3N2O 279.0740, found 279.0741.
Preparation of Alcohol 47. A solution of 140 mg (0.503 mmol) of
4-trifluoroacetylazobenzene, 46, in 3 mL of methanol was cooled in a
water bath, and 100 μL of 0.6 M NaOCH3 in methanol was added.
Sodium borohydride (94 mg, 2.485 mmol) was added in small portions
to the mixture, and stirring continued for 30 min. About 12 mL of ether
was added, and the mixture was carefully quenched by the addition of
10 mL of 1% HCl in water. The aqueous phase was separated, and the
ether extract was washed with water and a saturated NaCl solution. The
ether extract was dried over a mixture of Na2SO4 and MgSO4 and
filtered, and the solvent was removed using a rotary evaporator to give
138 mg of the crude product 47. This crude product was dissolved in 4
mL of ether, and 1.3 g of silica gel was added to the ether solution. The
solvent was removed using a rotary evaporator, and the dry powder was
then added to a column prepared from 6 g of silica gel and packed with
5% ether in pentane. The column was eluted with increasing amounts of
ether in pentane. The product 47 (129 mg, 91% yield) eluted with 15−
20% ether in pentane as an orange solid, mp 95−96 °C. 1H NMR of 47
Reaction of Chloride 53 in CH3CO2H. To 28 mg (0.153 mmol) of
chloride 53 was added a solution of 25 mg of 2,6-lutidine (0.234 mmol)
in 3 mL of CH3CO2H, and the mixture was kept at room temperature
for 130 min. The solution was transferred to a separatory funnel, and 6
mL of pentane was added, followed by 10 mL of water. The pentane
extract was washed with two additional portions of water and then a
NaHCO3 solution. After being dried over Na2SO4, the pentane solvent
was removed using a rotary evaporator, and the residue was filtered
through 250 mg of silica gel in a pipet using 5% ether in pentane.
Solvent removal gave 29 mg (92% yield) of the acetate 55 as a yellow
oil. 1H NMR (600 MHz, CDCl3): δ 7.68 (m, 2 H), 7.48−7.41 (m, 3 H),
2.16 (s, 3 H), 1.68 (s, 6 H). 13C{1H} NMR (150 MHz, CDCl3): δ
169.6, 151.57, 130.8, 129.0, 122.5, 101.6, 24.6, 22.1. HRMS (ESI): m/z
(M + Na)+ calculated for C11H14N2NaO2 229.0947, found 229.0942.
Reaction of Chloride 53 in CH3OH. Methanol (3.9 mL) was
added to 19 mg of chloride 53, and the mixture was kept at room
temperature for 30 min. Then, sodium methoxide (0.2 mL of 0.6 M in
methanol) was added. The methanol was removed using a rotary
evaporator, and 4 mL of pentane was added to the residue. The mixture
was washed with two portions of water, and the pentane extract was
dried over Na2SO4. After the removal of the pentane using a rotary
evaporator, the residue (15.8 mg) was filtered through 260 mg of silica
gel in a pipet using 2% ether in pentane. Solvent removal gave 14.4 mg
of the ether 57-(OCH3) as a yellow oil. 1H NMR (600 MHz, CDCl3): δ
7.73 (m, 2 H), 7.50−7.42 (m, 3 H), 3.51 (s, 3 H), 1.43 (s, 6 H).
13C{1H} NMR (150 MHz, CDCl3): δ 151.7, 130.8, 129.0, 122.4, 98.3,
51.0, 23.4. HRMS (ESI): m/z (M + Na)+ calculated for C10H14N2NaO
201.0998, found 201.0987.
Preparation of Azide 56. To a stirred solution of 30 mg of NaN3
(0.461 mmol) in 2.0 mL of DMSO was added a solution of 14 mg of
chloride 53 (0.077 mmol) in 100 μL of pentane dropwise. The mixture
was stirred for 30 min and then transferred to a separatory funnel with
10 mL of water and 4 mL of pentane. The pentane extract was washed
with two portions of water and then dried over Na2SO4. The solvent
was removed using a rotary evaporator, and the residue was filtered
through 200 mg of silica gel in a pipet using 2% ether in pentane.
Solvent removal gave 7.6 mg (49% yield) of azide 56 as a yellow oil. 1H
NMR (600 MHz, CDCl3): δ 7.60 (m, 2 H), 7.51−7.45 (m, 3 H), 1.58
(s, 6 H). 13C{1H} NMR (150 MHz, CDCl3): δ 151.0, 131.3, 129.1,
122.7, 86.5, 24.4. HRMS (ESI) for the phenylacetylene triazole
derivative:30 m/z (M + H)+ calculated for C17H18N5 292.1557, found
292.1553.
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Preparation of Chlorides 67 and 68. Using a procedure
analogous to the preparation of 53, dimethyl sulfoxide (231 mg;
2.957 mmol) was dissolved in 8 mL of dry THF, and the mixture was
cooled to −70 °C. To the stirred mixture was added oxalyl chloride
(0.20 mL; approximately 296 mg; 2.332 mmol) via syringe over about
10 s at −70 °C. The mixture was stirred between −60° and −65 °C for
20 min and then cooled to −78 °C. To the stirred mixture was then
added a solution of 450 mg (1.936 mmol) of the phenylhydrazone
derivative of 3-trimethylsilylcyclohexanone and 300 mg (2.970 mmol)
of Et3N in about 5 mL of THF dropwise over 15 min. After 20 min at
−78 °C, the mixture was allowed to warm to room temperature.
Pentane (10 mL) was then added, and the mixture was filtered using a
Buchner funnel to remove the Et3NHCl. The salts were washed with an
additional 5 mL of pentane. The clear orange solution was placed on a
rotary evaporator to remove the solvents. The oily residue was extracted
with 10 mL of pentane, and the orange pentane extract was filtered
through a small amount of MgSO4 in a pipet. The solvent was removed
from the pentane solution, and the residue was chromatographed on a
column prepared from 9.3 g of silica gel packed with 4% ether in
pentane. The column was eluted with 4% ether in pentane, and the
products eluted immediately with this solvent. Solvent removal gave
336 mg (65% yield) of a mixture of 67 and 68 in a 76:24 ratio as a yellow
oil. The relatively unstable chlorides were stored in a pentane solution
at −20 °C. Chlorides 67 and 68 gave no parent peak during the
attempted HRMS analysis. 1H NMR (600 MHz, CDCl3): δ 7.87−7.77
(m, 2 H), 7.53−7.46 (m, 3 H), 2.98−2.87 (m, 2 H), 2.76−2.6 (m, 2 H),
2.14 (t of t, J = 10.4, 9.7 Hz, 0.26 H), 1.85 (t of t, J = 11.0, 9.2 Hz, 0.74
H), 0.07 (s, 6.66 H), 0.02 (s, 2.34 H). 13C{1H} NMR of 67 (150 MHz,
CDCl3): δ 151.2, 131.3, 129.10, 122.98, 91.3, 39.2, 15.3, −3.5. 13C{1H}
NMR of 68 (150 MHz, CDCl3): δ 151.1, 131.5, 129.09, 123.00, 92.6,
37.9, 13.4, −3.4.
Reaction of Chlorides 67 and 68 in CH3CO2H. Chlorides 67 and
68 (53 mg; 0.199 mmol) in 5 mL of CH3CO2H containing 24 mg of
2,6-lutidine (0.224 mmol) were kept at 30−35 °C for 22.5 h. The
mixture was taken up into 10 mL of ether and 15 mL of pentane. The
solution was washed with three portions of water and then a dilute
NaHCO3 solution. After drying with Na2SO4 and MgSO4, the solution
was filtered, and the solvents were removed using a rotary evaporator.
The residue was filtered through 300 mg of silica gel using 3% ether in
pentane. Solvent removal gave 53 mg (92% yield) of a mixture of 71a
and 72a as a yellow oil. The 71a:72a ratio was determined to be 69:31
by the integration of the acetoxy signals at δ 2.16 and 2.21. 1H NMR of
71a (600 MHz, CDCl3): δ 7.75 (m, 2 H), 7.48−7.41 (m, 3 H), 2.70 (m,
2 H), 2.41 (m, 2 H), 2.16 (s, 3 H), 1.77 (m, 1 H), 0.048 (s, 9 H).
13C{1H} NMR of 71a (150 MHz, CDCl3): δ 169.4, 151.5, 130.8,
128.95, 122.7, 99.4, 34.6, 21.3, 12.9, −3.6. 1H NMR of 72a (600 MHz,
CDCl3): δ 7.72 (m, 2 H), 7.48−7.41 (m, 3 H), 2.67−2.62 (m, 4 H),
2.21 (s, 3 H), 1.78 (m, 1 H), 0.05 (s, 9 H). 13C{1H} NMR of 72a (150
MHz, CDCl3): δ 169.7, 151.3, 130.9, 128.93, 122.8, 100.9, 33.5, 21.6,
11.9, −3.1. HRMS (ESI): m/z (M + Na)+ calculated for
C15H22N2NaO2Si 313.1343, found 313.1331.
HRMS (ESI): m/z (M + H)+ calculated for C14H23N2OSi 263.1574,
found 263.1588.
Solvolytic Reactions. Details of the reactions of various substrates
in various solvents are given in the Supporting Information.
Kinetics Studies. All the details, as well as the pertinent first-order
plots, are given in the Supporting Information.
Computational Studies. Molecular orbital calculations were
performed using the Gaussian 16 series of programs.17 Structures
were characterized as energy minima via frequency calculations that
showed no negative frequencies. All transition states showed one
imaginary frequency. Values of E represent electronic energies and do
not include ZPVE (which are given in the Supporting Information).
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00140.
■
sı
Complete reference ref 17, details of the reactions of
substrates in various solvents, data used for the
determination of rate constants, 1H and 13C NMR spectra
of new compounds, and computational details (PDF)
FAIR data, including the primary NMR FID files, for
compounds 20, 25, 26, 46−48, 55−57, 67/68, 71a/72a,
and 71b/72b (ZIP)
AUTHOR INFORMATION
Corresponding Author
■
Xavier Creary − Department of Chemistry and Biochemistry,
University of Notre Dame, Notre Dame, Indiana 46556,
United States; orcid.org/0000-0002-1274-5769;
Email: creary.1@nd.edu
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00140
Notes
The author declares no competing financial interest.
REFERENCES
■
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Reaction of Chlorides 67 and 68 in CH3OH. A solution of 17.8
mg of chlorides 67 and 68 (0.067 mmol) in 3 mL of CH3OH was kept
at room temperature for 145 min. A NaOCH3 solution (0.16 mL of
0.510 M in methanol, 0.082 mmol) was added, and solvent was then
removed using a rotary evaporator. Pentane (3 mL) was then added,
and the mixture was washed with three portions of water. After drying
over a mixture of Na2SO4 and MgSO4, solvents were removed using a
rotary evaporator. The crude products were filtered through 0.5 g of
silica gel using 2% ether in pentane. Solvent removal using a rotary
evaporator gave 14.1 mg (80% yield) of a mixture of methyl ethers 71b
and 72b as a yellow oil. The 71b:72b ratio was determined to be 73:27
by the integration of the methoxy signals at δ 3.35 and 3.45. 1H NMR of
71b (600 MHz, CDCl3): δ 7.80 (m, 2 H), 7.50−7.43 (m, 3 H), 3.35 (s,
3 H), 2.43 (m, 2 H), 2.15 (m, 2 H), 1.35 (quintet, 1 H), 0.03 (s, 9 H).
13C{1H} NMR of 71b (150 MHz, CDCl3): δ 151.8, 130.8, 129.005,
122.6, 99.4, 50.8, 32.1, 9.8, −3.5. 1H NMR of 72b (600 MHz, CDCl3):
δ 7.76 (m, 2 H), 7.50−7.43 (m, 3 H), 2.38 (m, 2 H), 2.32 (m, 2 H), 1.65
(quintet, 1 H), −0.01 (s, 9 H). 13C{1H} NMR of 72b (150 MHz,
CDCl3): δ 151.6, 130.9, 129.012, 122.6, 100.8, 51.1, 31.5, 10.9, −3.3.
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