Mechanistic investigation on the reaction of 1,1-di-p-substituted phenyl-2,2-dinitroethylene with 1-benzyl-1,4-dihydronicotin-amide in oxygen saturated acetonitrile - Clear evidence for intermediate mechanism

Article abstract of DOI:10.1016/j.tetlet.2005.06.095

The reaction of 1-benzyl-1,4-dihydronicotinamide with a series of 1,1-di-p-substituted-phenyl-2,2-dinitroethylenes in oxygen-saturated acetonitrile produced various amounts of the corresponding ethanes and diaryl ketones according to the electronic structure of the substituent groups indicating a spectrum of intermediate mechanism between polar mechanism and SET mechanism.

Full text of DOI:10.1016/j.tetlet.2005.06.095

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 5739–5742
Mechanistic investigation on the reaction of
1,1-di-p-substituted phenyl-2,2-dinitroethylene with
1-benzyl-1,4-dihydronicotin-amide in oxygen saturated
acetonitrile—clear evidence for intermediate mechanism
a
Hua-Jian Xu,a Dan-Mei Dai,a You-Cheng Liu,a,b, Jing Li,
*
Shi-Wei Luoa and Yun-Dong Wuc,*
aDepartment of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
bNational Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China
cDepartment of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
Received 8 April 2005; revised 9 June 2005; accepted 13 June 2005
Available online 7 July 2005
Abstract—The reaction of 1-benzyl-1,4-dihydronicotinamide with a series of 1,1-di-p-substituted-phenyl-2,2-dinitroethylenes in oxy-
gen-saturated acetonitrile produced various amounts of the corresponding ethanes and diaryl ketones according to the electronic
structure of the substituent groups indicating a spectrum of intermediate mechanism between polar mechanism and SET
mechanism.
Ó 2005 Elsevier Ltd. All rights reserved.
The mechanism of equivalent hydride transfer from
coenzyme NADH models to a variety of substrates
has been studied by many investigators and continues
to be the area of interest.1–11 The focal issue of interest
is concerned with the dichotomy into direct hydride
(HÀ) transfer (polar mechanism) and multistep electron
transfer mechanism, involving electron transfer–proton
transfer–electron transfer (eÀ, H+, eÀ) or electron trans-
fer–hydrogen atom abstraction (eÀ–HÅ) (SET mecha-
nism). Pross–Shaik theory12 relates the polar pathway
and SET pathway in organic chemistry by Configura-
tion Mixing Model, which implies that the transition
states for both processes are likely to be similar. Pross13
has discussed the factors governing SET versus polar
pathways and indicated that an intermediate mechanism
is possible.
indicating an intermediate mechanism between polar
mechanism and electron transfer mechanism. The idea
of partial electron transfer had been suggested before
in the literature. Walling15 first noted that, in the reac-
tions of large activation energy in which single-electron
transfer would be expected to be endergonic, it might be
considered that charge transfer is only partial in the
rate-determining step. Bethell et al.16 studied the kinetics
and mechanism of the reaction of 9-arylfluoren-9-yl cat-
ions with polymethylbenzene in trifluoroacetic acid solu-
tion and concluded that the overall hydride transfer
proceeds through a transition state having considerable
electron transfer character and with loosening of the
transferred hydrogen. Bunting and Sindhuatmadja17
studied the kinetics and mechanism of the reduction of
2-methyl and 2-(Z-benzyl)-5-nitroisoquinolinium cation
by 1-(X-benzyl)-1,4-dihydronicotinamides and found
that the migrating hydrogen atom bears a À0.44 charge
in the transition state. Kreevoy et al.18 reported that the
reduction of pyridinium, quinolinium, isoquinolinium,
acridinium and other related cations by various 1,4-
dihydropyridines proceeds via a highly variable transi-
tion state structure with different fractional negative
charge developing on the migrating hydrogen atom.
Hoz and co-workers19 reported that, in any transition
Recently, we reported14 that the reaction of 1,1-diphen-
yl-2,2-dinitroethylene with 1-benzyl-1,4-dihydronicotin-
amide (BNAH) proceeds through a transition state of
partial diradical and partial covalent bonding character,
*
Corresponding authors. Tel.: +86 551 3603254; fax: +86 551 3631760
(Y.-C.L.); e-mail: ycliu@ustc.edu.cn
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.06.095

5740
H.-J. Xu et al. / Tetrahedron Letters 46 (2005) 5739–5742
H3CO
H3C
NO2
NO2
NO2
NO2
NO2
NO2
H3CO
H3C
3
1
2
Cl
F
F
O2N
NO2
NO2
NO2
NO2
NO2
NO2
Cl
6
5
4
Figure 1. Compounds 1–6.
state of Michael addition reaction, there is a partial
covalent bonding as well as a partial diradical character.
with dry oxygen for 10 min, another flask containing
dry acetonitrile was bubbled with dry oxygen for
10 min. A portion (5 ml) of the dry acetonitrile was
taken and added to the former flask. The reaction vessel
was then sealed and allowed to stand under oxygen at
room temperature in the dark for corresponding time
listed in Table 1. Hydrochloric acid (0.1 M, 1 ml) was
added, the mixture was extracted with chloroform and
the combined extract dried with Na2SO4. After evapora-
tion of the solvent, the residue was subjected to chroma-
tography on a silica gel column with chloroform as
eluent, and the pyridinium salt formed and unreacted
BNAH was retained on the column. The products were
then analyzed by GC–MS spectroscopy (see supplemen-
tary information).
In view of the fact that the oxygen-trapping experi-
ment14 could produce direct evidence for the diradica-
loid character of the transition state in the reaction of
BNAH with activated ethylenes, we thought it would
be worthwhile to extend the investigation to a series of
differently substituted 1,1-diaryl-2,2-dinitroethylenes
with the aim of finding the possibility of SET-polar
mechanistic spectrum. For this purpose, we have synthe-
sized five 1,1-di-p-substituted–phenyl-2,2-dinitroethyl-
enes (2–6, mono-p-substituted in the case of 6) and
carried out the reactions of 1–6 (Fig. 1) with BNAH in
oxygen-saturated acetonitrile and analyzed the products
by GC–MS spectroscopy. Herein, we wish to report the
results.
In general, substrates with electron withdrawing p-sub-
stitutents require shorter reaction times. The reaction
times were chosen so that the reactions gave high overall
yields. For each reaction, there are two major peaks,
which are well separated. They correspond to the reduc-
tion product 7 and the oxidation product 8 (Scheme 1).
Compounds 1–6 were prepared according to the litera-
ture.20 1-Benzyl-1,4-dihydronicotinamide (BNAH) was
prepared as described.21 A flask containing compounds
1–6 (0.05 mmol) and BNAH (0.05 mmol) was blown
Table 1. The molar ratios of 8 to 7 from the reactions of 1–6 with BNAH in O2-saturated acetonitrile
1
2
3
4
5
6
X
H
CH3
CH3
4.0
CH3O
CH3O
4.5
F
Cl
Cl
NO2
H
Y
H
F
Reaction time
Overall yields
Retention time of 8 (min)
Retention time of 7 (min)
8:7 (molar ratio)
2.5
92
2.5
94
2.0
96
1.5
98
91
90
7.53
10.89
0.62
10.20
12.82
0.37
13.56
15.56
0.36
7.03
10.59
0.82
11.32
14.56
0.88
11.67
15.72
0.53
X
X
X
Y
O2-saturated,
MeCN
in the dark
H
NO2
NO2
NO2
NO2
-
+
O
BNA Cl
+
BNAH
+
+
0.1 M HCl
H
Y
Y
8
7
Scheme 1.

H.-J. Xu et al. / Tetrahedron Letters 46 (2005) 5739–5742
5741
Ar1
Ar2
NO2
NO2
Ar1
Ar2
NO2
NO2
Ar1
Ar2
-e-
O
O2
O
O O
NO2
NO2
Ar1
Ar2
O
NO2
NO2
Ar1
Ar2
8
BNAH
+
BNAH
MeCN
H
H
NO2
NO2
transition state
Ar1
Ar2
NO2
NO2
Ar1
Ar2
H
7
Scheme 2.
The more polar product 7 has a longer retention time
than 8. The differences in retention times are over
2 min. The analytical results are listed in Table 1.
NAD+
NADH
CH
C
C
C
For each reaction, the reduction product 7 was domi-
nant. But the oxidation product 8 was also formed to
a considerable extent. By reference to our previous
report14 and the work of Hoz,19 it is plausible to propose
that the reactions of BNAH with 1–6 in oxygen-satu-
rated acetonitrile take place via a concerted electron
transfer-hydrogen atom transfer mechanism, schemati-
cally represented as shown in Scheme 2.
TS'
electron
transfer
TS
b
c
a
NADH
C
C
C-H bond formation
It is well documented that the reaction of benzylic radi-
cals with oxygen is diffusion controlled,22 so the forma-
tion of 8 may be taken as a quantitative measure of the
extent of diradical character of the transition state.
From the data listed in Table 1, it is seen that the relative
amount of ketone increases in the order of MeO <
Me < NO2 < H < F < Cl as the p-substituent group
changes in the series. This order is, except for the
NO2, in consistence with the electron withdrawing
power of the substituent groups.
Figure 3. Potential energy surface diagram for the reaction of NADH
model with compounds 1–6. Line (a) represents concerted hydride
transfer mechanism (polar mechanism), in which electron transfer and
hydrogen atom transfer with the formation of a C–H covalent bond
take place in complete concertedness; line (b) represents an interme-
diate mechanism in which electron transfer and covalent bond
formation are not in complete concertedness, electron transfer has
progressed further than hydrogen atom transfer, and the transition
state is of partial diradical and partial covalent bonding character; line
(c) represents electron transfer mechanism.
moving closer to the upper left corner in Fig. 3), and
there should be more oxygen trapping product; while
EDG substituents decrease the rate of reaction, the TS
will be relatively late and there should be less oxygen
trapping product. These are borne out by experiments.
A plot of the relative amount of diaryl ketones versus
23
Hammett r0 of the substituents is shown in Figure 2.
In order to rationalize the results, a potential energy sur-
face diagram is constructed as shown in Figure 3 by ref-
erence to the potential energy surface diagram given in
Ref. 13.
A special note must be made as regards the NO2 group.
NO2 is known to be a substituent group with a low
LUMO orbital,20 which can effectively stabilize a radica-
loid species by delocalizing the spin all over the group.
Thus, albeit compound 6 reacted with BNAH with the
fastest rate among the compounds studied, the yield of
8 from the reaction in oxygen-saturated acetonitrile
was of medium value (Table 1).
Since EWG substituents increase the rate of reaction, TS
will be relatively early (the perpendicular arrow head
1.2
1.0
Cl
In conclusion, the experimental results reported provide
clear evidence for the fact, due to the electronic effect
and steric effect of the substrate molecules, there exists
a mechanistic spectrum of intermediate mechanism be-
tween polar mechanism and SET mechanism in the title
reaction of BNAH with activated ethylenic compounds.
F
0.8
H
0.6
NO
2
CH
0.4
0.2
0.0
3
CHO
3
Acknowledgements
-0.3
0.0
0.3
σ0
0.6
0.9
The work was supported by National Natural Science
Foundation of China (Grant No. 20072036) and
Figure 2. Hammett plot for the molar ratio 8:7 versus r0.

5742
H.-J. Xu et al. / Tetrahedron Letters 46 (2005) 5739–5742
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Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2005.
06.095.
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