Elimination Reactions of (E)-2,4-Dinitrobenzaldehyde O-Benzoyloximes

Full text of DOI:10.1021/jo990752f

J . Org. Chem. 1999, 64, 8375-8378
8375
Notes
Ta ble 1. Ra te Con sta n ts for Elim in a tion s fr om
Elim in a tion Rea ction s of
(E)-2,4-Din itr oben za ld eh yd e
O-Ben zoyloxim es
(E)-2,4-(NO2)2C6H3CHdNOC(O)C6H4Xa P r om oted by R2NH
in MeCN a t 25.0 °C
102k2,c,d M-1 s-1
R2NH
X ) H
X ) p-MeO
X ) m-Br
X ) p-NO2
Bong Rae Cho,*,† Hack Sook Chung,† and
Sang Yong Pyun‡
Bz(i-Pr)NH
i-Bu2NH
i-Pr2NH
0.789
2.91
4.78
8.22
0.360
1.54
3.02
5.28
2.33
7.33
12.8
21.5
4.36
13.9
24.2
34.1
Department of Chemistry and Center for Electro- and
Photo-Responsive Molecules, Korea University,
1-Anamdong, Seoul 136-701, Korea, and Department of
Chemistry, Pukyong National University,
Pusan 608-737, Korea
2,6-DMP
[Substrate] ) 4.0 × 10-5 M. b [Base] ) 1.8 × 10-2 M. c Average
a
d
of three or more rate constants. Estimated uncertainty, (3%.
poor leaving groups, which should also increase the
negative charge density at the â-carbon in the transition
state.16 Furthermore, an sp2-hybridized â-carbon atom
should stabilize the negative charge density more than
an sp3-hybridized carbon atom.14,16 All of these factors
favor an E1cb or E1cb-like transition state. However,
such a transition state has never been observed in the
nitrile-forming syn-elimination reactions.
Received May 5, 1999
Extensive study of the structure-property relationship
revealed that the nitrile-forming syn eliminations from
(E)-benzaldehyde O-aryloximes proceed by the E2 mech-
anism via the E2-central transition state under various
conditions.1-10 Similarly, the E and Z isomers of benzal-
dehyde O-pivaloyloximes and benzaldehyde O-benzoyl-
oximes reacted with 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU) in MeCN by the same E2 mechanism, despite the
20000-36000-fold difference in rate.11,12 The transition
state for the anti-elimination reaction was slightly more
product-like with smaller degrees of proton transfer and
NR-OC(O)Ar bond cleavage, less negative charge devel-
opment at the â-carbon, and a greater extent of triple-
bond formation than that for the corresponding syn
elimination. Only a small difference in the transition-
state structure was noted. The results are somewhat
surprising since the latter has syn stereochemistry, a
poor leaving group, and a sp2-hybridized â-carbon atom.
It is well established that the transition state for the syn
elimination has more carbanion character than that for
anti elimination because of the poor overlap of the
developing p-orbitals.13-16 Moreover, carboxylates are
To determine whether a change to the E1cb mechanism
could be realized by introducing a more electron-
withdrawing â-aryl substituent, we studied the reactions
of (E)-2,4-dinitrobenzaldehyde O-benzoyloxime with
+
R2NH in MeCN and i-Pr2NH/i-Pr2NH2 in 70% MeCN-
(aq) (eq 1). This substrate is the most strongly activated
one studied so far in the (E)-benzaldehyde O-benzoyl-
oxime series.
† Korea University.
Resu lts
‡ Pukyong National University.
(1) Hegarty, A. F.; Tuohey, P. J . J . Chem. Soc., Perkin Trans. 2 1980,
1313-1317.
The (E)-2,4-dinitrobenzaldehyde O-benzoyloximes 1a-d
were synthesized by the reaction of (E)-2,4-dinitrobenz-
aldehyde oxime with substituted benzoyl chlorides, as
described previously.11,12 The reaction of 1a with
i-Pr2NH in MeCN produced (E)-2,4-dinitrobenzonitrile
in 93% yield. No trace of (E)-2,4-dinitrobenzaldoxime
could be detected by TLC.
(2) Cho, B. R.; Kim, K. D.; Lee, J . C.; Cho, N. S. J . Am. Chem. Soc.
1988, 110, 6145-6148.
(3) Cho, B. R.; Lee, J . C.; Cho, N. S.; Kim, K. D. J . Chem. Soc., Perkin
Trans. 2 1989, 489-492.
(4) Cho, B. R.; Min, B. K.; Lee, C. W.; J e, J . T. J . Org. Chem. 1991,
56, 5513-5516.
(5) Cho, B. R.; Kim, K. D.; Lee, J . C.; Cho, N. S. J . Am. Chem. Soc.
1991, 110, 6145.
Rates of reactions between 1a -d and R2NH in MeCN
were followed by monitoring the decrease in absorption
of the reactant at 280 nm, as described previously.11,12
Excellent pseudo-first-order kinetic plots, which covered
at least 3 half-lives, were obtained. Dividing the pseudo-
first-order rate constants by the base concentration
provided the second order-rate coefficients, k2, presented
in Table 1.
(6) Cho, B. R.; J ung, J .; Ahn, E. K. J . Am. Chem. Soc. 1992, 114,
3425-3458.
(7) Cho, B. R.; J e, J . T. J . Org. Chem. 1993, 58, 6190-6193.
(8) Cho, B. R.; Maing Yoon, C.-O.; Song, K. S. Tetrahedron Lett.
1995, 36, 3193-3196.
(9) Cho, B. R.; J ang, W. J .; Bartsch, R. A. J . Org. Chem. 1993, 58,
3901-3904.
(10) Cho, B. R.; Cho, N. S.; Song, K. S.; Son, K. N.; Kim, Y. K. J .
Org. Chem. 1998, 63, 3006-3009.
(11) Cho, B. R.; Cho, N. S.; Lee, S. K. J . Org. Chem. 1997, 62, 2230-
2233.
(12) Cho, B. R.; Chung, H. S.; Cho, N. S. J . Org. Chem. 1998, 63,
4685-4690.
(15) Saunders, W. H., J r.; Cockerill, A. F. Mechanism of Elimination
Reactions; Wiley: New York, 1973; pp 510-523.
(16) Gandler, J . R. In The Chemistry of Double Bonded Functional
Groups; Patai, S., Ed.; J ohn Wiley & Sons: Chichester, 1989; Vol. 2,
Part 1, pp 734-797.
(13) DePuy, C. H.; Naylor, C. G.; Beckman, J . A. J . Org. Chem. 1970,
35, 2750-2753.
(14) Dohner, B. R.; Saunders, W. H., J r. J . Am. Chem. Soc. 1986,
108, 245-259.
10.1021/jo990752f CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/14/1999

8376 J . Org. Chem., Vol. 64, No. 22, 1999
Notes
Ta ble 2. Br o1n sted â Va lu es for Nitr ile-F or m in g
Elim in a tion s fr om (E)-2,4-(NO2)2C6H3CHdNOC(O)C6H4Xa
P r om oted by R2NH in MeCN a t 25.0 °C
a
X
pKlg
â
p-MeO
H
m-Br
p-NO2
21.3
20.7
19.5
18.7
0.55 ( 0.05
0.47 ( 0.04
0.45 ( 0.05
0.43 ( 0.04
a
Reference 22.
Ta ble 3. Br o1n sted âlg Va lu es for Nitr ile-F or m in g
Elim in a tion s fr om (E)-2,4-(NO2)2C6H3CHdNOC(O)C6H4Xa
P r om oted by R2NH in MeCN a t 25.0 °C
a
R2NH
pKa
âlg
Bz(i-Pr)NH
i-Bu2NH
i-Pr2NH
16.8
18.2
18.5
18.9
- 0.41 ( 0.03
- 0.36 ( 0.02
- 0.35 ( 0.02
- 0.32 ( 0.01
2,6-DMP
a
Reference 23.
F igu r e 2. Reaction coordinate diagram for nitrile-forming
eliminations from (E)-2,4-dinitrobenzaldehyde O-benzoy-
loximes. The effects of the change to a better leaving group
and a stronger base are shown by the shift of the transition
state from A to B and A to C, respectively.
coefficient, pxy ) ∂â/∂pKlg ) ∂âlg/∂pKBH, that describes the
interaction between the base catalyst and the leaving
group.16,17 The observed increase in the |âlg| values as the
catalyst is less basic is another manifestation of this
effect, i.e., pxy ) ∂âlg/∂pKBH > 0. On the More-O’Ferall-
J encks energy diagram shown in Figure 2, a change to a
better leaving group will raise the energy of the top edge
of the diagram. The transition state on the vertical
reaction coordinate will then move slightly toward the
right as depicted by a shift from A to B on the energy
diagram, resulting in a decrease in â (vide supra).18,19
Similarly, a stronger base will raise the energy of the
right side of the energy diagram and shift the transition
state from A to C to decrease the extent of NR-OC(O)Ar
bond cleavage. The positive pxy coefficients are inconsis-
tent with an E1cb mechanism for which pxy ) 0 is
expected, but provide additional support for the concerted
E2 mechanism.16,17 All of these results are very similar
to those for closely related eliminations from (E)- and (Z)-
benzaldehyde O-benzoyloximes.12
F igu r e 1. Plot of kobs vs buffer concentration for elimination
from (E)-2,4-(NO2)2C6H3CHdNOC(O)C6H5 promoted by i-Pr2-
NH/i-Pr2NH2 in 70% MeCN(aq) at 25.0 °C.
+
The k2 values showed excellent correlation with the pKa
values of the promoting base on Bro¨nsted plots (not
shown). The â value decreases as the leaving group is
made less basic (Table 2). Similarly, the k2 values
correlated satisfactorily with the leaving group pKa
values (plots not shown). The |âlg| value decreases with
a stronger base (Table 3).
+
Elimination reactions of 1a with i-Pr2NH/i-Pr2NH2
It is conceivable that a change to a more protic solvent
may lower the energy of the carbanion intermediate,
which may in turn induce a change in the reaction
mechanism from E2 to E1cb. To assess this possibility,
we have investigated the elimination reactions of 1a with
buffer in 70% MeCN(aq) were also briefly studied. The
kobs values are summarized in Table 4. The kobs values
increase linearly with buffer concentration (Figure 1).
Discu ssion
+
i-Pr2NH/i-Pr2NH2 buffer in 70% MeCN(aq). Figure 1
Mech a n ism of Elim in a tion fr om 1 P r om oted by
R2NH in MeCN. Results of the kinetic investigations
and product studies clearly establish that the reactions
of (E)-2,4-dinitrobenzaldehyde O-benzoyloximes 1 with
R2NH in MeCN proceed via an E2 mechanism. Since the
reactions produced only elimination products and exhib-
ited second-order kinetics, all but bimolecular pathways
can be ruled out. In addition, an E1cb mechanism is
negated by the substantial values of â and |âlg|.15,16
This conclusion is supported by the interaction coef-
ficients. Table 2 shows that the â values for 1 decrease
slightly as the leaving groups are made less basic. The
result can be described by a positive pxy interaction
shows that the plot of kobs vs buffer concentration is a
straight line passing through the origin, i.e., kobs ) k2-
[buffer]. If the reaction proceeds via a carbanion inter-
mediate, the rate equation can be expressed as kobs
)
k1k2[B]/(k-1[BH+] + k2) (Scheme 1).16 This predicts that
the plot of kobs should change from a straight line at a
low buffer concentration, i.e., kobs ) k1[B] when k-1[BH+]
, k2, to a plateau at a higher base concentration, i.e.,
(17) Gandler, J . R.; J encks, W. P. J . Am. Chem. Soc. 1982, 104,
1937-1951.
(18) J encks, W. P. Chem. Rev. 1985, 85, 511-527.
(19) Lowry, T. H.; Richardson, K. S. Mechanism and Theory in
Organic Chemistry; Harper and Row: New York, 1987; pp 591-616.

Notes
J . Org. Chem., Vol. 64, No. 22, 1999 8377
a
+
Ta ble 4. Ra te Con sta n ts for Elim in a tion fr om (E)-2,4-(NO2)2C6H3CHdNOC(O)C6H5 P r om oted by i-P r 2NH/i-P r 2NH2 in
70% MeCN(a q) a t 25.0 °Cb
102[buffer],c M
103kobs d,e s-1s
0.200
0.138
0.400
0.245
0.600
0.347
1.00
0.530
1.40
0.696
1.80
0.839
3.00
1.18
5.00
1.66
10.0
3.69
,
a
b
d
[Substrate] ) 4.0 × 10-5 M. Ionic strength ) 1.0 M (Bu4N+Br-). c Buffer ratio ) 1.0. Average of three or more rate constants.
e Estimated uncertainty, (3%.
Sch em e 1
of the â-aryl groups should be nearly orthogonal to the
developing negative charge at the â-carbon in the transi-
tion state.20 This would predict that the electronic effect
of the â-substituent should be transmitted to the reaction
site only through an inductive effect. Furthermore, the
negative charge density developed on the â-carbon would
be less sensitive to the substituent effect because it
should be more stable than that on a sp3 hybridized
carbon atom. It appears that the nitrile-forming transi-
tion states are intrinsically insensitive to the reactant
structure variations because of the lack of resonance
stabilization of charge density on the â-carbon and the
increased carbanion stabilizing ability of the sp2-hybrid-
ized â-carbon atom.
Ta ble 5. Rela tive Ra te, Br o1n sted â, a n d âlg Va lu es for
Elim in a tion s fr om (E)-YC6H4CHdNO(O)C6H4X
Y ) Ha
DBU-MeCNb
19.4
Y ) 2,4-(NO2)2
base-solvent
R2NH-MeCN
18.5c
10
0.47 ( 0.04
-0.35 ( 0.02
pKa
relative rated
1
âd
âlg
>0.5e
-0.49 ( 0.02
Exp er im en ta l Section
a
b
Reference 12. DBU ) 1,8-diazabicyclo[5.4.0]undec-7-ene.
c R2NH ) i-Pr2NH. X ) H. e Estimated from kH/kD ) 3.3 (see
d
Mater ials. (E)-2,4-Dinitrobenzaldehyde O-benzoyloximes 1a-d
were synthesized by the reaction of (E)-2,4-dinitrobenzalde-
hydeoxime with benzoyl chlorides, as described elsewhere.11,12
The spectral and analytical data for the compounds were
consistent with the proposed structures. The yield, melting point,
IR (KBr, cm-1), NMR (CDCl3, J values are given in Hz), and
combustion analysis data for the new compounds follow.
(E)-2,4-(NO2)2C6H3CHdNOC(O)C6H5 (1a ): yield 70%; mp
172-174 °C; IR 1759 (CdO), 1589 (CdN); NMR δ 9.22 (s, 1H),
9.02 (d, 1H, J ) 2.4), 8.57 (dd, 1H, J ) 8.7, 2.3), 8.48 (d, 1H, J
) 8.4), 8.15 (d, 2H, J ) 8.4), 7.66 (t, 1H, J ) 7.3), 7.53 (t, 2H, J
) 7.8). Anal. Calcd for C14H9N3O6: C, 53.34; H, 2.88; N, 13.33.
Found: C, 53.20; H, 2.56; N,13.70.
(E)-2,4-(NO2)2C6H3CHdNOC(O)C6H4-p-OCH3 (1a ): yield
56%; mp 158 °C; IR 1748 (CdO), 1600 (CdN); NMR δ 9.21 (s,
1H), 9.03 (d, 1H, J ) 2.4), 8.57 (dd, 1H, J ) 8.7, 2.3), 8.50 (d,
1H, J ) 8.4), 8.12 (d, 2H, J ) 8.6), 7.01 (d, 2H, J ) 8.6), 3.91 (s,
3H). Anal. Calcd for C15H11N3O7: C, 52.18; H, 3.21; N, 12.17.
Found: C, 52.23; H, 3.18; N,12.17.
(E)-2,4-(NO2)2C6H3CHdNOC(O)C6H4-m -Br (1c): yield 56%;
mp 178 °C; IR 1756 (CdO), 1582 (CdN); NMR δ 9.25 (s, 1H),
9.05 (d, 1H, J ) 2.1), 8.59 (dd, 1H, J ) 8.7, 2.3), 8.47 (d, 1H, J
) 8.7), 8.30 (s, 1H), 8.10 (d, 1H, J ) 7.8), 7.80 (d, 1H, J ) 7.2),
7.42 (t, 1H, J ) 7.7). Anal. Calcd for C14H8BrN3O6: C, 42.66; H,
2.05; N, 10.66. Found: C, 42.86; H, 2.13; N, 10.70.
(E)-2,4-(NO2)2C6H3CHdNOC(O)C6H4-p-NO2 (1d): yield 62%;
mp 172-174 °C; IR 1763 (CdO), 1589 (CdN); NMR δ 9.27 (s,
1H), 9.06 (d, 1H, J ) 2.4), 8.61 (dd, 1H, J ) 8.4, 2.3), 8.46 (d,
1H, J ) 8.4), 8.39 (d, 2H, J ) 8.9), 8.35 (d, 2H, J ) 8.9). Anal.
Calcd for C14H8N4O8: C, 46.68; H, 2.24; N, 15.55. Found: C,
46.80; H, 2.12; N, 15.29.
text).
kobs ) k2 when k-1[BH+] . k2. Hence the straight line
observed in Figure 1 provides strong evidence that the
reaction proceeds by the E2 mechanism even under with
additional favoring conditions for the E1cb mechanism.
E ffect of â-Ar yl Gr ou p on t h e Nit r ile-F or m in g
Tr a n sition Sta te. Table 5 shows that the rate of
elimination from 1a is only 10-fold faster than that from
the unsubstituted (E)-benzaldehyde O-benzoyloxime. Al-
though this result may in part be attributed to the
weaker basicity of i-Pr2NH than DBU, the difference is
surprisingly small considering the large difference in the
electron-withdrawing ability of the â-aryl substituent.11
Comparison of the transition-state parameters reveals
that the structure of the transition states for these two
reactions are also similar. It was previously reported that
the DBU-promoted elimination from (E)-benzaldehyde
O-benzoyloxime proceed via a slightly E1cb-like transi-
tion state, in which the Câ-H bond cleavage has pro-
gressed to a greater extent than the NR-OAr bond
rupture.11,12 Although a direct comparison between the
kH/kD and â values is not possible, â ) 0.47 for elimination
from 1 appears to indicate a smaller extent of proton
transfer than the kH/kD ) 3.3 value for the former since
the latter was attributed to more than half proton
transfer.11,12 In addition, the smaller |âlg| value for the
former can also be explained with a lesser degree of NR-
OAr bond cleavage. These results indicate that the
transition state for elimination from 1 is slightly more
reactant-like with lesser extents of Câ-H and NR-OAr
bond cleavage. However, it should be noted that the
difference is remarkably small considering the large
difference in the â-aryl substituent.
Buffer solutions were prepared by dissolving equivalent
+
amounts of i-Pr2NH and i-Pr2NH2 in 70% MeCN(aq). In all
cases, the ionic strength was maintained at 0.10 M with
Bu4N+Br-.
P r od u ct Stu d ies. The products of the reaction between 1a
and i-Pr2NH in MeCN were identified using a more concentrated
solution. A solution of 1a was allowed to react with 10 equiv of
i-Pr2NH in 15 mL of MeCN for 3 h at room temperature. The
solvent was evaporated, and the product was taken up in CH2-
Cl2. The solution was washed thoroughly with water, dried over
MgSO4, and evaporated. The product was 2,4-dinitrobenzonitrile
with mp 105 °C (lit.21 mp 104-5 °C); yield 0.36 g (93%).
The small difference in the transition-state structures
may be attributed to the geometry of the reactant
structure. It has been well established that the benzal-
doxime esters have planar structures.11,12,20 Hence, if the
planarity is retained in the transition state, the π orbitals
(21) Dictionary of Organic Compounds; Mack Printing Co.: Easton,
PA, 1982; Vol. 2, p 2258.
(22) Coetzee, J . F. Prog. Phys. Org, Chem. 1965, 4, 45-92.
(23) Cho, B. R.; Lee, S. J .; Kim, Y. K. J . Org. Chem. 1995, 60, 2072-
2076.
(20) Cho, B. R.; Cho, N. S.; Song, S. H.; Lee, S. K. J . Org. Chem.
1998, 63, 8304-8309.

8378 J . Org. Chem., Vol. 64, No. 22, 1999
Notes
Kin etic Stu d ies. Reactions of 1a -d with R2NH in MeCN
and 1a with of i-Pr2NH and i-Pr2NH2+ buffer in 70% MeCN(aq)
were followed by monitoring the decrease in absorption at280
nm with reaction time by a UV-vis spectrophotometer, as
described before.11,12 For all reactions, the UV absorption of the
reactants decreased and that of the products increased with
time. Except for the reactions of 1a , clean isosbestic points were
observed at 245-250 nm.
of their solutions in MeCN with the UV spectrophotometer.11,12
No change in melting point or UV spectrum was detected for at
least 1 month at -10 °C.
Ack n ow led gm en t. This research was supported by
Basic Science Research Institute Program, Ministry of
Education, 1998 (Project No. BSRI-98-3406).
Con tr ol Exp er im en ts. The stabilities of 1a -d were deter-
mined by measuring the melting point and periodical scanning
J O990752F