Elimination reactions of (E)-2,4-dinitrobenzaldehyde O-benzoyloximes promoted by R2NH/R2NH2+ in 70 mol % MeCN(aq). Change of reaction mechanism

Article abstract of DOI:10.1021/jo8019412

(Chemical Equation Presented) Elimination reactions of (E)-2,4-(NO ₂)₂C₆H₃CH=NOC(O)-C₆H ₄X (1) promoted by R₂NH/R₂NH₂ ⁺ in 70 mol % MeCN(aq) have been studied kinetically. The reactions are second-order and exhibit Broensted β = 0.27-0.32 and |β_lg| = 0.28-0.32. The result can be described by a negligible P_xy interaction coefficient, p_xy = ?β/ ?pK_lg = ?β_lg/?pK_BH ≈ 0, which describes the interaction between the base catalyst and the leaving group. The negligible p_xy coefficients are consistent with the (E1cb) _irr mechanism.

Full text of DOI:10.1021/jo8019412

TABLE 1. Second-Order Rate Constants for Nitrile-Forming
Elimination Reactions of
Elimination from (E)-2,4-(NO2)2C6H3CHdNOC(O)C6H4Xa Promoted
(E)-2,4-Dinitrobenzaldehyde O-Benzoyloximes
b,c
+
by R2NH/R2NH2 in 70 mol % MeCN(aq) at 25.0 °C
+
Promoted by R2NH/R2NH2 in 70 mol %
102k2, M-1s-1
f,g
MeCN(aq). Change of Reaction Mechanism
d
e
R2NH
pKa
X ) H
X ) p-OMe
X ) m-Cl
X ) p-NO2
Bz(i-Pr)NH
i-Bu2NH
16.8
18.2
18.5
18.9
1.04
3.20
2.09
4.79
0.820
1.86
1.38
3.12
2.12
7.40
4.43
10.7
4.24
12.8
8.50
19.8
Sang Yong Pyun*,† and Bong Rae Cho*,‡
i-Pr2NH
Department of Chemistry, Pukyong National UniVersity,
Pusan 608-737, Korea, and Department of Chemistry, Korea
UniVersity, 1-Anamdong, Seoul, 136-701, Korea
2,6-DMPh
a [Substrate] ) 5.0 × 10-5 M. b [R2NH]/[R2NH2+] ) 1.0. c µ ) 0.1
d
(Bu4N+Br). [R2NH] ) 2.0 × 10-2M. e Reference 4. f Average of three
or more rate constants. g Estimated uncertainty, (3%. h cis-2,6-
sypyun@pknu.ac.kr; chobr@korea.ac.kr
Dimethylpiperidine.
ReceiVed September 2, 2008
nism. However, the conclusion was based on the linear increase
in kobs with buffer concentration. Therefore, a detailed
structure-reactivity relationship study seems necessary to
provide a more convincing evidence for the proposed mechanism.
To gain a better insight into the nitrile-forming eliminations,
+
we have now studied the reactions 1a-d with R2NH/R2NH2
in 70 mol % MeCN(aq) (eq 1). By comparing with the existing
data for 1a-d with R2NH in MeCN, the effects of the
base-solvent on the nitrile-forming elimination was assessed.
Elimination reactions of (E)-2,4-(NO2)2C6H3CHdNOC(O)-
+
C6H4X (1) promoted by R2NH/R2NH2 in 70 mol %
MeCN(aq) have been studied kinetically. The reactions are
second-order and exhibit Bro¨nsted ꢀ ) 0.27-0.32 and |ꢀlg|
) 0.28-0.32. The result can be described by a negligible
pxy interaction coefficient, pxy ) ∂ꢀ/∂pKlg ) ∂ꢀlg/∂pKBH ≈ 0,
which describes the interaction between the base catalyst and
the leaving group. The negligible pxy coefficients are
consistent with the (E1cb)irr mechanism.
Product Study. (E)-2,4-Dinitrobenzaldehyde O-benzoyl oximes
1a-d were available from a previous study.2 The reactions of
1a with i-Bu2NH/i-Bu2NH2+ in 70 mol % MeCN(aq) produced
2,4-dinitrobenzonitrile and benzoate. The isolated yield of 2,4-
dinitrobenzonitrile from a large-scale reaction was 94%. No trace
of (E)-2,4-dinitrobenzaldehyde oxime could be detected by TLC,
negating the possibility of the hydrolysis reaction.
We have reported previously that elimination reactions of (E)-
and (Z)-YC6H3CHdNOC(O)C6H4X promoted by R2NH in
MeCN proceed by the E2 mechanism.1 The transition state for
the syn-elimination from the (E)-isomer shifted slightly toward
E1cb-like with greater extent of Cꢀ-H bond cleavage, more
negative charge development at ꢀ-carbon, and a smaller extent
of triple bond formation than that of anti-elimination from the
(Z)-isomer. To determine whether a change to an E1cb mech-
anism could be realized by introducing a more electron-
withdrawing ꢀ-aryl substituent, we studied the elimination
reactions of (E)-2,4-(NO2)2C6H3CHdNOC(O)C6H4X (1a-d)
with R2NH in MeCN.2 However, only a modest change in the
transition-state structure was observed. Moreover, an E2 mech-
anism was proposed for the reaction of 1a with i-Pr2NH/i-
Kinetic Study. The rates of elimination reaction were
followed by monitoring the decrease in the absorption at the
λmax for the substrates in the range of 258-280 nm as
described.1,3 In all cases, the ionic strength was maintained to
be 0.1 M with Bu4N+Br-. Excellent pseudo-first-order kinetics
plots, which covered at least 3 half-lives, were obtained. Plots
+
of kobs for the reactions of 1a and 1d with i-Bu2NH/i-Bu2NH2
+
and i-Pr2NH/i-Pr2NH2 in 70 mol % MeCN(aq) against base
concentration were straight lines passing through the origin,
indicating that the reactions are second order, first order to the
substrate, and first order to the base.2 Moreover, the k2 values
calculated from the slopes of the plots were in excellent
agreement (within (3%) with the k2 calculated by using a single
data point. Hence, the rate constants for the base-promoted
eliminations from 1a-dwere determined at a single base
concentration. The k2 values were obtained by dividing the kobs
by the base concentration. Values of k2 for eliminations from
1a-d are summarized in Table 1. Except for the rate data
+
Pr2NH2 in 70 mol % MeCN(aq), a solvent capable of
stabilizing the developing negative charge density at the
ꢀ-carbon, and thereby additionally favoring the E1cb mecha-
† Pukyong National University.
‡ Korea University.
(1) Cho, B. R.; Chung, H. S.; Cho, N. S. J. Org. Chem. 1998, 63, 4685–
4690.
(2) Cho, B. R.; Chung, H. S.; Pyun, S. Y. J. Org. Chem. 1999, 64, 8375–
8378.
(3) Cho, B. R.; Cho, N. S.; Lee, S. K. J. Org. Chem. 1997, 62, 2230–2233.
10.1021/jo8019412 CCC: $40.75
Published on Web 11/04/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 9451–9453 9451

TABLE 3. Bro¨nsted ꢀlg Values for elimination from
(E)-2,4-(NO2)2C6H3CHdNOC(O)C6H4X Promoted by R2NH/R2NH2
in 70 mol % MeCN(aq) at 25.0 °C
+
R2NH Bz (i-Pr)NH
i-Bu2NH
18.2
-0.28 ( 0.02 -0.32 ( 0.01 -0.30 ( 0.01 -0.31 ( 0.01
i-Pr2NH
2,6-DMPb
a
pKa
16.8
18.5
18.9
ꢀlg
a Reference 5. b cis-2,6-Dimethylpiperidine.
SCHEME 1
FIGURE 1. Bro¨nsted plots for the elimination from (E)-2,4-
(NO2)2C6H3CHdNOC(O)C6H4X promoted by R2NH/R2NH2+ in 70 mol
% MeCN(aq) at 25.0 °C [X ) H (1a, b), p-OMe (1b, 9), m-Cl (1c,
2), p-NO2 (1d, 1)].
products and exhibited second-order kinetics, all but bimolecular
elimination pathways can be negated. The (E1cb)ip and internal
return mechanisms were ruled out by the observed general base
catalysis with the Bro¨nsted ꢀ values ranging from 0.28 to 0.32
because these mechanisms would exhibit either a specific base
catalysis or Bro¨nsted ꢀ values near unity.6,7 Hence, the most
likely mechanism for this bimolecular process is either E2 or
E1cb. If the reaction proceeds via a carbanion intermediate, the
rate equation can be expressed as kobs ) k1k2′[B]/(k-1[BH+] +
k2′) (Scheme 1).6 The (E1cb)R mechanism requires that the first
step must be reversible, i.e., k-1[BH+] . k2′, and the rate
expression can be simplified to kobs ) k1k2′[B]/(k-1[BH+]). This
would predict that the kobs should remain constant regardless
of the buffer concentration because [B]/[BH+] ) 1.0 is
maintained throughout the reaction. Therefore, the (Elcb)R
mechanism is ruled out by the linear dependence of the kobs
values on the base concentration. On the other hand, the ꢀ )
0.28-0.32 and |ꢀlg| ) 0.28-0.32 are consistent with an E2
mechanism with limited cleavage of the Cꢀ-H and
NR-OC(O)Ar bonds in the transition state, and a mechanism
in which k1 is the rate limiting [(E1cb)irr], for which a small or
negligible leaving group effect is expected.7
The distinction between the two mechanisms has been made
by the interaction coefficients. Table 2 shows that the ꢀ values
for 1a remain almost the same within experimental error
regardless of the base strength. The result can be described by
a negligible pxy interaction coefficient, pxy ) ∂ꢀ/∂pKlg ≈ 0, which
describes the interaction between the base catalyst and the
leaving group.6,8-11 The similar |ꢀlg| values for all bases is
another manifestation of this effect, pxy ) ∂ꢀlg/∂pKBH ≈ 0 (Table
3). On the More-O’Ferrall-Jencks energy diagram shown in
Figure 3, a change to a better leaving group will raise the energy
of the top edge of the diagram. The transition state on the
horizontal coordinate will remain at nearly the same position
because there is no diagonal character. This would predict
negligible change in ꢀ.8 Similarly, a change to a stronger base
will raise the energy of the right side of the diagram. The
FIGURE 2. Plots of log k2 versus p Klg values of the leaving group
for the elimination from (E)-2,4-(NO2)2C6H3CH)NOC(O)C6H4X (1a-
+
d) promoted by R2NH/R2NH2 in 70 mol % MeCN(aq) at 25.0 °C
[R2NH ) Bz(i-Pr)NH(9), i-Bu2NH(•), i-Pr2NH(2), 2,6-DMP(1)].
TABLE 2. Bro¨nsted ꢀ Values for Elimination from
(E)-2,4-(NO2)2C6H3CHdNOC(O)C6H4X (1a-d)a Promoted by
+
R2NH/R2NH2 in 70 mol % MeCN(aq) at 25.0 °C
X ) p-OMe
X ) H
20.7
0.32 ( 0.02
X ) m-Cl
X ) p-NO2
a
pKlg
21.3
0.27 ( 0.01
19.5
0.34( 0.04
18.7
0.32 ( 0.02
ꢀ
a Reference 4.
determined with i-Pr2NH, the rate increased with the base
strength of the promoting base and the leaving group ability.
The slower rate of eliminations from 1a-d with i-Pr2NH than
with i-Bu2NH as the base can be attributed to the greater steric
requirement of the former.
The plots of k2 values for 1a-d against the pKa values of
the base are depicted in Figure 1. The plots are linear with
excellent correlations, if the data for i-Pr2NH is excluded.
Therefore, the ꢀ values were calculated from the straight lines
without the data for i-Pr2NH. Similarly, the elimination rates
determined with different leaving groups correlated reasonably
well with the leaving group pKlg values (Figure 2). The ꢀ and
|ꢀlg| values are in the range of 0.27-0.32 and 0.28-0.32,
respectively. The ꢀ and |ꢀlg| values remained nearly the same
within experimental error for all leaving groups and bases
employed in this study (Tables 2 and 3).
(4) Coetzee, J. F. Prog. Phys. Org. Chem. 1965, 4, 45–92.
(5) Cho, B. R.; Lee, S. J.; Kim, Y. K. J. Org. Chem. 1995, 60, 2072–2076.
(6) Gandler, J. R. In The Chemistry of Double Bonded Functional Groups;
Patai, S., Ed.; John Wiley and Sons: Chichester, 1989; Vol. 2, Part 1, pp 734-
797.
(7) Lowry, T. H.; Richardson, K. S. Mechanism and Theory in Organic
Chemistry; Harper and Row: New York, 1987; pp 591-616.
(8) Jencks, W. P. Chem. ReV. 1985, 85, 511–527.
(9) Gandler, J. R.; Jencks, W. P. J. Am. Chem. Soc. 1982, 104, 1937–1951.
(10) Gandler, J. R.; Yokohama, T. J. Am. Chem. Soc. 1984, 106, 130–135.
(11) Gandler, J. R.; Storer, J. W.; Ohlberg, D. A. A. J. Am. Chem. Soc. 1990,
112, 7756–7762.
Mechanism of Elimination. The mechanism of elimination
for 1a-d promoted by R2NH/R2NH2+ in 70 mol % MeCN(aq)
have been elucidated by the results of kinetic investigations and
product studies. Because the reactions produced only elimination
9452 J. Org. Chem. Vol. 73, No. 23, 2008

negative charge developed at the ꢀ-carbon in the transition state
is better stabilized by solvation in more protic 70 mol %
MeCN(aq), the transition state should be less sensitive to the
base strength. This would predict a smaller ꢀ value, as observed.
Moreover, the negative charge should be transferred from the
ꢀ-carbon toward the R-nitrogen to form partial triple bond and
to break the NR-OC(O)Ar bond. If a smaller amount of negative
charge is transferred from the ꢀ-carbon, the extent of
NR-OC(O)Ar bond cleavage should be smaller too. The most
interesting result from this study is the change of the reaction
mechanism from E2 to (E1cb)irr by the base-solvent variation
as revealed by the interaction coefficients (pxy > 0 f pxy ∼ 0)
(Table 4). It appears that the change in the elimination reaction
mechanism has been realized by the combined effects of strongly
electron-withdrawing ꢀ-aryl substituents, intrinsically carbanion
stabilizing sp2-hybridized ꢀ-carbon, syn-stereochemistry and
enhanced anion-solvating ability of more protic solvent.
FIGURE 3. Reaction coordinate diagram for nitrile-forming elimina-
tions from (E)-2,4-dinitrobenzaldehyde O-benzoyloximes. (Top) The
effect of the change to a stronger base on the horizontal reaction
coordinate is shown by the shift of the transition state from A to B.
The effect of the change to a better leaving group is omitted because
there will be little shift. (Center) The effects of the change to a stronger
base and a better leaving group on the diagonal reaction coordinate
are shown by the shifts from C to D and C to E, respectively. These
effects can be described by pxy > 0.
Experimental Section
Materials. (E)-2,4-Dinitrobenzaldehyde O-benzoyloximes 1a-d
were available from previous investigations.2 Reagent-grade ac-
etonitrile and secondary amine were fractionally distilled from
CaH2. Buffer solutions were prepared by dissolving equivalent
amounts of R2NH and R2NH2+ in 70 mol % MeCN(aq). In all cases,
the ionic strength was maintained to be 0.1 with Bu4N+Br-.
Kinetic Studies. All of the reactions were followed using a
UV-vis spectrophotometer with thermostated cuvette holders.
Reactions were monitored by the decrease in the absorption of the
substrate at 258-280 nm under pseudo-first-order condition
employing at least 400-fold excess of the base. The pseudo-first-
order rate constants were divided by the base concentration to afford
the second-order rate constants, k2.
Product Studies. The product from the reaction of 1a with
i-Bu2NH/i-Bu2NH2+ in 70 mol % MeCN(aq) was identified by using
more concentrated solution as described previously.2 A solution
of 0.5 g (1.59 mmol) of 1a and an excess amount of base in the
appropriate base (15 mL) was stirred for 7 h at room temperature.
The solvent was removed in vacuo and the residue was extracted
with CH2Cl2 and washed thoroughly with water until all of the
amine, ammonium salt, and the benzoate were completely removed.
The product was 2,4-dinitrobenzonitrile with mp 103 °C (lit.13 mp
104-105 °C). The yield of 2,4-dinitrobenzonitrile was 0.29 g
(94%).
TABLE 4. Effect of the Base-Solvent on the Nitrile-Forming
Eliminations from (E)-2,4-(NO2)2C6H3CHdNOC(O)C6H5
base-solvent R2NH-MeCNa R2NH/R2NH2+-70 mol % MeCN(aq)
rel rate (k2)b
1.0
0.6
ꢀ
0.47 ( 0.04
-0.41 ( 0.01
0.040 ( 0.005
0.32 ( 0.02
-0.28 ( 0.02
∼0
c
ꢀlg
pxy
a Reference 2. b R2NH ) i-Bu2NH. c R2NH ) Bz(i-Pr)NH.
transition state on the horizontal coordinate will then move
toward the right as depicted by a shift from A to B, resulting in
little change in |ꢀlg|.8 The negligible pxy coefficients are
inconsistent with the E2 mechanism for which pxy > 0 is
expected (Figure 3) but provide a strong evidence for the
(E1cb)irr mechanism.6,8-11
Effect of Base-Solvent. Table 4 shows that the rate of
elimination from 1a decreases slightly as the base-solvent is
changed from i-Bu2NH-MeCN to i-Bu2NH/i-Bu2NH2+ in 70 mol
% MeCN(aq), presumably due to the decreased basicity in more
protic solvent.12 The extent of Cꢀ-H and NR-OC(O)Ar bond
cleavage decreased remarkably as revealed by the large decrease
in the Bro¨nsted ꢀ and |ꢀlg| values by the same variation of the
base-solvent system (Table 4).
Control Experiments. The stabilities of 1a-d were determined
as reported.1,2 The solutions of 1 in MeCN were stable for at least
5 weeks when stored in the refrigerator.
Acknowledgment. This work was supported by the Korea
Science and Engineering Foundation (KOSEF) grant funded by
the Korea Ministry of Education, Science, and Technology (No.
R0A-2007-000-20027-0).
Thechangeinthetransition-statestructurewiththebase-solvent
variation can be attributed to a solvent effect. If the partial
JO8019412
(12) Dargo, R. S.; Zoltewicz, J. A. J. Org. Chem. 1994, 59, 2824–2830, and
references cited therein.
(13) Dictionary of Organic Compounds; Mack Printing Co.: Easton, PA,
1982; Vol. 2, p 2258.
J. Org. Chem. Vol. 73, No. 23, 2008 9453