Mechanism of elimination from (1-anilino-1-cyanoethyl)benzene promoted by sodium methoxide in methanol

Full text of DOI:10.1021/jo960254w

5656
J . Org. Chem. 1996, 61, 5656-5658
Mech a n ism of Elim in a tion fr om
(1-An ilin o-1-cya n oeth yl)ben zen e P r om oted
by Sod iu m Meth oxid e in Meth a n ol
Bong Rae Cho,*,1a Yoon Chul Oh,1a Sang Hae Lee,1a and
Young J a Park1b
Department of Chemistry, Korea University,
1-Anamdong, Seoul 136-701, Korea, and Department of
Chemistry, Sook Myung Women’s University,
Seoul 140-742, Korea
Received February 7, 1996
In tr od u ction
Extensive studies on the imine-forming elimination
reactions have revealed that the reactions are much more
facile than the corresponding alkene-forming elimina-
tions and proceed via E2-central or E1-like transition
states.2 For MeONa-promoted eliminations from
ArCH2N(OSO2Ar)R, a competing E2 and (E1)ip mecha-
nism was also reported.3 All of these studies utilized 1,
in which the leaving group is attached to the nitrogen.
Accordingly, many of the characteristics of the imine-
forming eliminations have been attributed to the weaker
strength of the N-X bond and greater CdN bond energy
than those involved in the corresponding alkene-forming
eliminations.
F igu r e 1. ORTEP representation of the (1-anilino-1-cyano-
ethyl)benzene structure.
the reactions between (1-anilino-1-cyanoethyl)benzenes
3 with MeONa in MeOH (eq 1). We have determined
In contrast, little is known about the imine-forming
eliminations from 2, in which the leaving group is
attached to the carbon. Since C-X and N-H bonds are
stronger than N-X and C-H bonds, respectively,4,5
eliminations from 1 are expected to be more exothermic
than those from 2. On the other hand, the N-H bond is
more acidic than the C-H bond.6,7 Hence, if the acidity
of the â-proton is more important, the latter should react
at a faster rate. However, the relative importance of
these two opposing factors on the imine-forming elimina-
tions has not been investigated in detail.
the X-ray structure of the reactant and measured the
reaction rates. The mechanism of the reactions is as-
sessed by the use of the transition state parameters. The
results of these studies are reported here.
Resu lts a n d Discu ssion
(1-Anilino-1-cyanoethyl)benzenes 3 were synthesized
by reacting aniline, acetophenone, and NaCN by the
literature method.8 The X-ray structure of 3a reveals
that the two phenyl groups are nearly orthogonal to each
other, and the dihedral angle between the N-H and the
C-CN bonds is 105.2° (Figure 1), which is close to 90°,
which is the most unfavorable angle for elimination
reactions.9 Therefore, the high temperature required for
the pyrolytic elimination from 3a may in part be ascribed
to the unfavorable dihedral angle.
Reaction of 3a with MeONa in MeOH produced only
N-phenylacetophenonimine. Rates of eliminations from
3 were followed by monitoring the increase in the
absorption at 243-244 nm. Rate constants for MeONa-
promoted eliminations from 3 are listed in Table 1. The
second-order rate constant k2 ) 2.81 × 10-4 M-1 s-1 at
40.0 °C for MeONa-promoted elimination from 3a is
approximately 130-fold smaller than k2 ) 3.65 × 10-2 M-1
s-1 for MeONa-promoted eliminations from N-chloro-N-
methylbenzylamine at 39.0 °C.10 Although a direct
comparison of these rate constants may not be very
meaningful because the two reactions proceed by differ-
ent mechanisms (vide infra), the slower rate of 3a can
It has been reported that the pyrolytic elimination of
(1-anilino-1-cyanoethyl)benzene proceeds at 210 °C to
afford N-phenylacetophenonimine in high yield.8 The
result is somewhat surprising considering the facility of
the imine-forming elimination reactions. In order to add
to the meager store of information available concerning
imine-forming eliminations from 2, we have investigated
(1) (a) Korea University. (b) Sook Myung Women's University.
(2) Hoffman, R. V.; Bartsch, R. A.; Cho, B. R. Acc. Chem. Res. 1989,
22, 211-217.
(3) Cho, B. R.; Pyun, S. Y. J . Am. Chem. Soc. 1991, 113, 3920-
3924.
(4) Bond energies for C-H, C-Cl, CH3-OH, N-H, N-Cl, and
CH3N-OH are 85, 80, 80, 62, 90, and 50, respectively,5 indicating that
the N-H and C-X bonds are stronger than the C-H and N-X bonds.
(5) Dean, J . A. Handbook of Organic Chemistry; McGraw-Hill: New
York, 1987; pp 3-13-3-37.
(6) The pKa values of HCl, HCN, C6H5NH2, and C6H5CH3 in DMSO
are 1.8, 12.9, 30.6, and 43, respectively.7 Although the corresponding
values determined in MeOH are not available in the literature, the
relative acidities may be assumed to be nearly the same in both
solvents.
(9) Bartsch, R. A.; Zavada, J . Chem. Rev. 1980, 80, 453-494.
(10) Bartsch, R. A.; Cho, B. R. J . Am. Chem. Soc. 1979, 101, 3587-
3591.
(7) Bordwell, F. G. Acc. Chem. Res. 1986, 21, 456-463.
(8) Dew, E. N.; Richie, P. D. Chem. Ind. 1969, 51-52.
S0022-3263(96)00254-X CCC: $12.00 © 1996 American Chemical Society

Notes
J . Org. Chem., Vol. 61, No. 16, 1996 5657
Ta ble 1. Secon d -Or d er Ra te Con sta n ts for Elim in a tion s
fr om XC6H4NHC(CN)(CH3)C6H5 P r om oted by MeONa in
nism (Table 2). An electron-withdrawing substituent
would increase the acidity of the N-H bond to enhance
the equilibrium constant for the first step. On the other
hand, it should also stabilize the negative charge devel-
oped at the nitrogen atom to decrease the rate of
elimination. A combination of these two opposing factors
should give rise to a small F value, as observed.15 The
activation parameters calculated for this reaction are also
in accord with this interpretation. The enthalpies of
activation for eliminations from 3a and N-chloro-N-
methylbenzylamine are the same despite the poorer
leaving group and unfavorable dihedral angle in the
former (vide supra). This result underlines the impor-
tance of the acidity of the â-proton in determining the
activation enthalpy. In contrast, the entropy of activation
for 3a is more negative than that for the latter by
approximately 11 eu. Since more solvent reorganization
would be required to solvate the more carbanionic transi-
tion state, the entropy of activation should be more
negative. Hence, the large difference in rates results
from an entropic factor.
a
MeOH
X
T, °C
[MeONa]
104k2, M-1 s-3 b,c
H
H
40.0
40.0
40.0
50.0
60.0
40.0
40.0
1.00
2.91 ( 0.01
2.75 ( 0.01
2.50 ( 0.02
6.28 ( 0.05
14.9 ( 0.1
8.13 ( 0.01
7.66 ( 0.01
0.510
0.640
1.00
1.00
1.00
Hd
H
H
m-Cl
m-Cl
0.760
a
b
[Substrate] ) (2-3) × 10-5 M. k2 ) kobs/[MeONa]. c Average
d
and standard deviation for two or more kinetic runs. The base-
solvent was MeONa-MeOD.
Ta ble 2. Tr a n sition Sta te P a r a m eter s for Elim in a tion s
fr om Ar CH2N(Cl)CH3 a n d Ar NHC(CN)(CH3)P h P r om oted
by MeONa in MeOH
a
ArCH2N(Cl)CH3
ArNHC(CN)(CH3)Ph
rel rate
kH/kD
130
1
6.0 ( 0.1
1.52 ( 0.06
16.6 ( 0.1
-12.1 ( 0.3
<2.5b
F
1.1 ( 0.1
16.3 ( 0.9
-22.7 ( 1.6
∆Hq, kcal/mol
∆Sq, eu
In conclusion, the reactions of 3 with MeONa in MeOH
proceed by the (E1cB)R mechanism. It appears that the
concerted E2 mechanism is disfavored by the poor leaving
group and the unfavorable dihedral angle, and the
(E1cB)R mechanism becomes the favored alternative
probably because the nitrogen anion can be stabilized by
solvation in MeOH.
a
b
MeOD
Reference 10. Estimated from k2MeOH/k2
) 1.1 and the
maximum solvent isotope effect (see text).
at least in part be attributed to the poor leaving group
ability of CN and the unfavorable dihedral angle.11
The reactions are second order as indicated by the
pseudo-first-order kinetics and nearly identical k2 values
for 2- to 4-fold variations in base concentration (Table
1). Therefore, all but bimolecular mechanism can be
ruled out. In addition, the rate of â-protium exchange
was much faster than the elimination reaction (see
Experimental Section). This result clearly establishes
that the reaction proceeds by the (E1cB)R mechanism,
in which the preequilibrium deprotonation is followed by
the rate-limiting elimination (eq 2).
Exp er im en ta l Section
Ma ter ia ls. (1-Anilino-1-cyanoethyl)benzenes 3a ,b were syn-
thesized by reacting aniline, acetophenone, and NaCN by the
literature method.8 N-Arylacetophenonimines 4a ,b were ob-
tained by the pyrolysis of 3a ,b at 210 °C as reported in the
literature.8 The melting points and the spectroscopic data of
the compounds were consistent with the structures.
X-r a y Cr ysta llogr a p h y. The compound was crystallized
from ethanol solution. Crystal data were obtained with using
an Enraf-Nonius CAD-4 diffractometer with graphite-monochro-
mated Cu KR radiation (λ ) 1.5416 A). The crystal (C15H14N2,
Mr ) 222.28) is monoclinic, P21, with a ) 5.929(1) Å, b ) 8.427(1)
Å, c ) 12.500(1) Å, â ) 99.91(1)°, Z ) 2, F(000) ) 236, T ) 293
K, Dc ) 1.20 g/cm3.
The 1087 independent reflections were measured with the
range of 2o e 2θ e 130°, of which there were 1074 reflections
with |Fo| > 4σ|Fo|. The structure was solved by direct methods
and refined by the full-matrix least-squares using the program
SHELXS-93.16 The final R and weighted Rw values were 0.086
and 0.161 for 1074 observed reflections, respectively. The final
atomic coordinates and thermal parameters for the non-
hydrogen atoms, bond lengths, bond angles, and torsion angles
are available from one of the authors (Y.J .P.) and have been
deposited with the Cambridge Crystallographic Data Centre.17
Kin etic Stu d ies. All of the reactions were followed using a
UV-vis spectrophotometer with thermostated cuvette holders.
Reactions were monitored by the increase in the absorption of
the product at 243 and 244 nm for 3a and 3b, respectively, under
pseudo-first-order conditions employing at least a 104-fold excess
The primary isotope effect was estimated from the rate
ratio, k2MeOH/k2MeOD ) 1.1, for reactions of 3a with MeONa
in MeOH and MeOD. Since the N-H bond must be
completely converted into N-D in MeOD before the
elimination reaction takes place (vide supra), this value
includes both the primary isotope effect and the medium
effect. For MeONa-promoted deprotonation reaction in
MeOH, the maximum solvent isotope effect has been
estimated to be KD/KH ) 2.5.13 Hence, the primary
isotope effect value for this reaction should be less than
2.5 (Table 2). The small isotope effect value is in good
agreement with the (E1cB)R mechanism, in which the
proton transfer occurs before the rate-limiting step.14 The
Hammett F value of 1.1 calculated with the rate data for
3a and 3b provides additional support for this mecha-
(14) (a) Lowry, T. H.; Richardson, K. S. Mechanism and Theory in
Organic Chemistry; Harper and Row: New York, 1987; pp 591-560.
(b) Gandler, J . R. In The Chemistry of Double Bonded Functional
Groups; Patai, S., Ed.; Wiley: Chichester, 1989; Vol. 2, Part 1, pp 734-
797.
(15) Cary, F. A.; Sundberg, R. J . Advanced Organic Chemistry, 3rd
ed.; Plenum Press: New York, 1990; Part A, pp 196-209.
(16) Sheldrick, G. M. SHELXS-86 and SHELXL-93, Program for
Crystal Structure Determination; Cambridge University Press: Cam-
bridge, 1986, 1993.
(17) The author has deposited atomic coordinates for (1-anilino-1-
cyanoethyl)benzene with the Cambridge Crystallographic Data Centre.
The coordinates can be obtained, on request, from the Director,
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge,
CB2 1EZ, UK.
(11) A reviewer raised a question whether the solid-state structure
for 3a is the same as that in MeOH. An ab initio calculation with the
Gaussian 94 program with the STO-3G basis set12 reveals that the
gas phase structure is very similar to that in the solid state except
that the dihedral angle between the N-H and C-CN bonds is 81.605°.
Therefore, it seems reasonable to assume that the solution-state
structure for 3a should also be similar to that in the solid-state.
(12) Gaussian 94, Gaussian Inc., Pittsburgh, PA, 1995.
(13) (a) Gold, V; Morris, K. P.; Wilcox, C. F. J . Chem. Soc., Perkin
Trans. 2 1982, 1615-1620. (b) More O'Ferall, R. A. J . Chem. Soc.,
Chem. Commun. 1969, 114-115.

5658 J . Org. Chem., Vol. 61, No. 16, 1996
Notes
of base as described before.3,10 In almost every case, plots of
-ln (A∞ - At/A∞ - Ao) vs time were linear over at least 2 half-
lives. The slope was the pseudo-first-order rate constant.
However, when the methoxide ion concentration was lower than
0.51 M, the reactions were too slow to follow to completion
conveniently. Therefore, a Guggenheim method was employed.
H-D Exch a n ge Exp er im en t. The H-D exchange experi-
ment was conducted by dissolving a small amount of 3a in
CD3OD. The NMR spectrum immediately after preparing the
sample showed that the N-H signal that appeared at δ 4.2 in
CDCl3 was completely absent, indicating that the exchange rate
is reasonably fast.
the aqueous layer with petroleum ether. Evaporation of the
solvent produced 0.50 g (57%) of N-phenylacetophenonimine as
a yellow solid: mp 38-41 °C (lit.8 mp 37-41 °C).
Con tr ol Exp er im en ts. The stability of 3 and 4 and their
solutions was determined by measuring the melting point and
periodical scanning of the solutions with the UV spectropho-
tometer. No change in melting point or UV spectrum was
detected for 3 and its solution during 4 months in the refrigera-
tor. However, the dilute solution of 4 in MeOH (10-5 M) started
to hydrolyze to acetophenone and aniline by the small amount
of water present as an impurity after 12 h at room temperature.
P r od u ct St u d ies. The yields of N-arylacetophenonimine,
determined by comparing the UV absorbances of the infinity
samples of the kinetic runs with those of authentic samples of
4, were in the range 75-100%. To isolate the elimination
product, (1-anilino-1-cyanoethyl)benzene (3a ) (1.0 g, 4.5 mmol)
and MeONa (65 mmol) were reacted in 35 mL of MeOH for 20
h at room temperature. The product was isolated by extracting
Ack n ow led gm en t. This research was supported in
part by OCRC-KOSEF and Basic Science Research
Institute Program, Ministry of Education, 1995 (Project
No. BSRI-95-3406).
J O960254W