Thermodynamic diagnosis of the properties and mechanism of dihydropyridine-type compounds as hydride source in acetonitrile with molecule id card

Article abstract of DOI:10.1021/jp911137p

A series of 45 dihydropyridine-type organic compounds as hydride source were designed and synthesized. The thermodynamic driving forces (defined as enthalpy changes or redox potentials in this work) of the dihydropyridines to release hydride anions, hydrogen atoms (hydrogen for short), and electrons in acetonitrile,the thermodynamic driving forces of the radical cations of the dihydropyridines to release protons and hydrogens in acetonitrile, and the thermodynamic driving forces of the neutral pyridine-type radicals of the dihydropyridines to release electron in acetonitrile were determined by using titration calorimetry and electrochemical methods. The rates and activation parameters of hydride transfer from the dihydropyridines to acridinium perclorate, a well-known hydride acceptor, were determined by using UV-vis absorption spectroscopy technique. The relationship between the thermodynamic driving forces and kinetic rate of the hydride transfer was examined. Thermodynamic characteristic graph (TCG) of the dihydropyridines as an efficient Molecule ID Card was introduced. The TCG can be used to quantitatively diagnose or predict the characteristic chemical properties of the dihydropyridines and their various reaction intermediates. The mechanism of hydride transfer from the dihydropyridines to acridinium perclorate was diagnosed and elucidated by using the determined thermodynamic parameters and the activation parameters..

Full text of DOI:10.1021/jp911137p

2058
J. Phys. Chem. B 2010, 114, 2058–2075
Thermodynamic Diagnosis of the Properties and Mechanism of Dihydropyridine-Type
Compounds as Hydride Source in Acetonitrile with “Molecule ID Card”
Xiao-Qing Zhu,* Yue Tan, and Chao-Tun Cao
State Key Laboratory of Elemento-Organic Chemistry, Department of Chemistry, Nankai UniVersity,
Tianjin 300071, China
ReceiVed: NoVember 23, 2009; ReVised Manuscript ReceiVed: December 19, 2009
A series of 45 dihydropyridine-type organic compounds as hydride source were designed and synthesized.
The thermodynamic driving forces (defined as enthalpy changes or redox potentials in this work) of the
dihydropyridines to release hydride anions, hydrogen atoms (hydrogen for short), and electrons in acetonitrile,
the thermodynamic driving forces of the radical cations of the dihydropyridines to release protons and hydrogens
in acetonitrile, and the thermodynamic driving forces of the neutral pyridine-type radicals of the
dihydropyridines to release electron in acetonitrile were determined by using titration calorimetry and
electrochemical methods. The rates and activation parameters of hydride transfer from the dihydropyridines
to acridinium perclorate, a well-known hydride acceptor, were determined by using UV-vis absorption
spectroscopy technique. The relationship between the thermodynamic driving forces and kinetic rate of the
hydride transfer was examined. Thermodynamic characteristic graph (TCG) of the dihydropyridines as an
efficient “Molecule ID Card” was introduced. The TCG can be used to quantitatively diagnose or predict the
characteristic chemical properties of the dihydropyridines and their various reaction intermediates. The
mechanism of hydride transfer from the dihydropyridines to acridinium perclorate was diagnosed and elucidated
by using the determined thermodynamic parameters and the activation parameters.
Introduction
The advantages of dihydropyridine-type organic hydrides are the
following: (i) dihydropyridine-type organic hydrides have the
same or similar active center structure as the natural NAD(P)H
coenzymes, which make the man-made dihydropyridine-type
organic hydrides usable as models of NAD(P)H to mimic
NAD(P)H reduction in vivo; (ii) man-made dihydropyridine-
type organic hydrides can be easily synthesized in the laboratory
on a large scale; and (iii) man-made dihydropyridine-type
organic hydrides like natural NAD(P)H are easy to recycle for
use. But, from past publications on man-made dihydropyridine-
type organic hydrides, it is clear that, although there have been
a lot of various man-made dihydropyridine-type organic hydrides
designed and synthesized in the laboratory, and applications of
them as organic reducing agents, hydrogen-storage materials,
and molecule probe, etc., and they have been extensively
investigated, the fundamental thermodynamic parameters, es-
pecially the thermodynamic driving forces of the organic
hydrides to release hydride anions in solution, have not been
systematically investigated; in fact, no thermodynamic driving
forces of the dihydropyridine-type organic hydrides to release
hydride anion in solution has been available from the literature
until now except a few NAD(P)H models.9f,36 It is evident that
the terrible lack of knowledge about the thermodynamic driving
forces of the man-made dihydropyridine-type organic hydrides
must cause a lot of difficulties to predict the relative activity
order of the extensively existing dihydropyridine-type organic
hydrides as reducing agents, to design new dihydropyridine-
type organic hydrides with higher power of releasing hydride
anion, and to develop the application of the dihydropyridine-
type organic hydrides as new hydride source, etc. The key reason
for the lack of thermodynamic parameters until now is that no
appropriate methods including efficient experimental method
and reliable theoretical method have been established. Several
years ago, we embarked on a major project to experimentally
Organic hydride compounds (organic hydrides for short in
this paper) are one class of very important organic compounds
that can provide hydride anions in chemical and biochemical
reactions.1 Because they play very important roles in the
processes of biological reductions and bioantioxidations, natural
organic hydrides, such as NAD(P)H, FADH2, F420 coenzyme,
tetrahydrofolate, and ascorbic acid (vitamin C), have been the
focus of interest for many chemists and biochemists in the past
several decades.2-6 Recently, man-made organic hydrides have
been also attracting extensive and increasing attention of
chemists and biochemists, the main reason is that the man-made
organic hydrides have many important roles and extensive
applications in various chemical fields, e.g., as models of some
important natural organic hydrides to examine the mechanisms
of hydride transfer from the natural organic hydrides in vivo;7-20
as organic reducing agents to take the place of inorganic
hydrides, e.g., NaBH4, LiAlH4, etc. to efficiently reduce various
unsaturated organic compounds, such as olefins, aldehydes,
ketones, epoxy compounds, and imines;21-25 as hydrogen-stored
materials to release hydrogen gas by reacting with protonic
acids;26 as functional molecular blocks to construct various
molecule devices,27-29 and as various molecular probes to
explore the essence of living phenomena,30,31 etc. In fact, studies
on man-made organic hydrides have made the chemistry of
organic hydrides a new and hot field of chemistry.32 By
examining the publications on the man-made organic hydrides,
it is found that among the various man-made organic hydrides,
dihydropyridine and its various derivatives as a class of
dihydropyridine-type organic hydrides have received much more
special attention of chemists and biochemists than the others.33-35
* To whom correspondence should be addressed. E-mail: xqzhu@
nankai.edu.cn.
10.1021/jp911137p  2010 American Chemical Society
Published on Web 01/14/2010

Dihydropyridine-Type Compounds as Hydride Source
J. Phys. Chem. B, Vol. 114, No. 5, 2010 2059
SCHEME 1: Structures of the Dihydropyridine-Type Organic Hydrides (XH) Examined in This Work
SCHEME 2: Possible Pathways of the
Dihydropyridine-Type Organic Hydrides (XH) to Release
Hydride Anions
of the 45 dihydropyridine-type organic hydrides (XH) and their
corresponding pyridine-type neutral radicals (X•) were deter-
mined in acetonitrile by using electrochemical methods CV and
OSWV (Figures 1 and 2), and the detailed experimental results
are summarized in Table 1. The molar enthalpy changes (∆Hr)
of hydride transfer from the dihydropyridine-type organic
-
hydrides XH to 9-phenylxanthium perclorate (PhXn+ClO4 ) (eq
determine the thermodynamic driving forces of various natural
and man-made organic hydrides to release hydride anions in
solution; one of the main purposes was to develop the
thermodynamic driving force scale of various organic hydrides
to release hydride anions in solution.9f,35,37 In this work, 45
dihydropyridine-type organic hydrides (XH) (Scheme 1) were
designed and synthesized and the thermodynamic driving forces
of them to release hydride anions in acetonitrile were examined
systematically.
Figure 1. Cyclic voltammogram (CV) and Osteryong square wave
voltammogram (OSWV) of 9H in anhydrous deaerated acetonitrile
solution containing 0.1 M (n-Bu)4NPF6 as supporting electrolyte: CV
graph (full line), OSWV graph (dashed line).
As the process of the dihydropyridine-type organic hydrides
(XH) to release hydride anions could involve multistep mech-
anisms, such as e--H+-e-, e--H•, and H•-e- (Scheme 2),8-20
the thermodynamic driving forces of XH to release hydrogen
atoms, the thermodynamic driving forces of XH•+ to release
protons and to release hydrogen atoms and the thermodynamic
driving forces of X• to release electrons in solution are also
very important and urgently required for chemists and biochem-
ists to elucidate the hydride transfers mechanism and to predict
and diagnose the characteristic chemical properties of the various
reaction intermediates of XH. In this work, these thermodynamic
parameters were also examined.
Results
The 45 dihydropyridine-type organic hydrides (XH) were
synthesized in this work according to conventional and conve-
nient synthetic strategies,38,39 and the target products were
identified by H NMR and MS; the detailed synthetic routes
are provided in the Supporting Information. Oxidation potentials
Figure 2. Cyclic voltammogram (CV) and Osteryong square wave
voltammogram (OSWV) of 9+ in anhydrous deaerated acetonitrile
solution containing 0.1 M (n-Bu)4NPF6 as supporting electrolyte: CV
graph (full line), OSWV graph (dashed line).
1

2060 J. Phys. Chem. B, Vol. 114, No. 5, 2010
Zhu et al.
TABLE 1: Reaction Enthalpy Changes of Hydride Transfer
from XH to PhXn+ClO4 in Acetonitrile (kcal mol-1) and
-
Oxidation Potentials of XH and X• in Acetonitrile (V versus
Fc+/0), Measured by Using CV and OSWV Methods,
Respectively
Eox(XH)b
Eox(X•)b
org hydrides
(XH)
∆Hra
CV
OSWV
CV
OSWV
1H
p-CH3O
p-CH3
p-H
-33.7
-33.2
-32.6
-32.5
-31.8
-30.5
0.241
0.253
0.259
0.266
0.279
0.311
0.204
0.211
0.219
0.224
0.237
0.268
-1.463
-1.458
-1.448
-1.445
-1.436
-1.405
-1.432
-1.427
-1.419
-1.415
-1.407
-1.374
p-F
p-Cl
p-CN
2H
p-CH3O
p-CH3
p-H
-30.6
-30.3
-29.7
-29.6
-29.2
-27.8
0.338
0.351
0.361
0.366
0.381
0.408
0.302
0.312
0.323
0.329
0.344
0.370
-1.369
-1.36
-1.347
-1.341
-1.326
-1.295
-1.329
-1.318
-1.310
-1.306
-1.295
-1.265
Figure 3. Isothermal titration calorimetry (ITC) for the reaction heat
of 2H (G ) H) with 9-phenylxanthylium perclorate (PhXn+ClO4-) in
acetonitrile at 298 K. Titration was conducted by adding 10 µL of
p-F
PhXn+ClO4 (3.27 mM) every 300s into the acetonitrile containing
-
p-Cl
p-CN
3H
2H (G ) H) (ca. 12.08 mM).
p-CH3O
p-CH3
p-H
-31.9
-31.6
-31.0
-30.9
-30.2
-28.9
0.374
0.385
0.402
0.406
0.413
0.438
0.337
0.348
0.361
0.365
0.375
0.401
-1.394
-1.389
-1.37
-1.366
-1.359
-1.325
-1.363
-1.355
-1.341
-1.339
-1.329
-1.295
in this work was defined as the enthalpy changes of XH to
release hydride anions in acetonitrile (eqs 1 and 2), which can
be obtained from the reaction enthalpy change of the hydride
transfer from XH to 9-phenylxanthylium perclorate
(PhXn+ClO4-) in acetonitrile (eqs 3 and 4). In eq 4, ∆Hr is the
enthalpy change of the reaction of eq 3 in acetonitrile, which
can be determined by using titration calorimetry (Figure 3);
p-F
p-Cl
p-CN
4H
p-CH3O
p-CH3
p-H
p-F
p-CN
5H
-27.1
-26.7
-26.3
-26.2
-24.2
0.443
0.455
0.470
0.476
0.508
0.407
0.418
0.431
0.434
0.471
-1.217
-1.213
-1.207
-1.203
-1.169
-1.187
-1.181
-1.176
-1.172
-1.139
∆HH A(PhXn+) is the hydride affinity of PhXn+ in acetonitrile
-
(i.e., the molar enthalpy change of PhXn+ to obtain hydride
anions in acetonitrile), which is available from our previous
work (-96.8 kcal/mol).40 The detailed enthalpy changes of the
45 XH to release hydride anions in acetonitrile are summarized
in Table 2.
p-CH3O
p-CH3
p-H
-26.6
-26.2
-25.5
-25.4
-24.4
-22.9
-29.3
-33.0
-30.9
-43.8
-48.8
-35.3
-28.6
-28.0
-29.5
0.490
0.501
0.517
0.522
0.531
0.557
0.390
0.233
0.303
0.038
-0.070
0.170
0.394
0.363
0.251
0.454
0.464
0.479
0.484
0.495
0.521
0.370
0.199
0.259
0.014
-0.094
0.142
0.370
0.332
0.222
-1.224
-1.216
-1.202
-1.200
-1.191
-1.159
-1.380
-1.485
-1.393
-1.642
-1.710
-1.478
-1.406
-1.154
-1.154
-1.195
-1.187
-1.175
-1.171
-1.159
-1.131
-1.352
-1.463
-1.340
-1.618
-1.682
-1.458
-1.386
-1.125
-1.125
p-F
p-Cl
p-CN
6H
7H
8H
9H
10H
11H
12H
13H
14H
15H (R ))
CH3
Et
pr
i-pr
-36.1
-35.3
-36.0
-35.6
-35.5
-21.0
-22.9
0.170
0.176
0.167
0.180
0.168
0.380
0.150
0.136
0.136
0.136
0.150
0.140
0.348
0.115
-1.492
-1.500
-1.490
-1.508
-1.687
-1.046
-0.959
-1.470
-1.480
-1.468
-1.484
-1.464
-1.000
-0.924
The thermodynamic driving forces of XH to release hydrogen
atoms and the thermodynamic driving forces of XH•+ to release
protons and to release hydrogen atoms in acetonitrile are also
defined as the corresponding enthalpy changes of XH to release
hydrogen atoms and of XH•+ to release protons and to release
hydrogen atoms in acetonitrile, respectively. It is evident that
these enthalpy change values can be used to measure hydrogen-
donating abilities of XH and proton-donating and hydrogen-
donating abilities of XH•+, respectively. In order to obtain the
enthalpy change values of the 45 XH to release hydrogen atoms
in acetonitrile and the enthalpy change values of the 45 XH•+
to release protons and to release hydrogen atoms in acetonitrile,
three thermodynamic cycles were constructed according to the
chemical process of XH to release hydride anions in acetonitrile
(Scheme 3). From the three thermodynamic cycles, three eqs
n-butyl
16H
17H
a ∆Hr obtained from the reaction heat of eq 3 by switching the
sign; the latter was measured by titration calorimetry in acetonitrile
at 25 °C. The data given in kcal/mol were average values of at least
three independent runs. The reproducibility is (0.5 kcal mol-1
.
b Measured by CV and OSWV methods in acetonitrile at 25 °C, the
unit in volts vs Fc+/0 and reproducible to 5 mV or better.
3) were measured by using titration calorimetry in acetonitrile
(Figure 3), the detailed experimental results are also listed in
Table 1.
The thermodynamic driving force of the dihydropyridine-type
organic hydrides (XH) to release hydride anions in acetonitrile

Dihydropyridine-Type Compounds as Hydride Source
J. Phys. Chem. B, Vol. 114, No. 5, 2010 2061
TABLE 2: Molar Enthalpy Changes of XH to Release Hydride Anions and Hydrogen Atoms and Molar Enthalpy Changes of
XH•+ To Release Hydrogen Atoms and Protons (kcal mol-1) as Well as Oxidation Potentials of XH and X• in Acetonitrile (V
versus Fc+/0
)
∆HH D(XH)a
∆HHD(XH)b
∆HHD(XH•+)b
∆HPD(XH•+)b
E°ox(XH)c
E°ox(X•)c
-
XH
1H
p-CH3O
p-CH3
p-H
p-F
p-Cl
p-CN
2H
63.1
63.6
64.2
64.3
65.0
66.3
69.9
70.3
70.7
70.7
71.2
71.8
32.2
32.5
32.9
32.9
33.3
33.9
12.0
12.2
12.4
12.3
12.6
12.4
0.204
0.211
0.219
0.224
0.237
0.268
-1.432
-1.427
-1.419
-1.415
-1.407
-1.374
p-CH3O
p-CH3
p-H
p-F
p-Cl
66.2
66.5
67.1
67.2
67.6
69.0
70.6
70.7
71.1
71.1
71.2
72.0
33.0
33.1
33.4
33.4
33.4
34.2
10.5
10.3
10.4
10.3
10.1
10.2
0.302
0.312
0.323
0.329
0.344
0.370
-1.329
-1.318
-1.310
-1.306
-1.295
-1.265
p-CN
3H
p-CH3O
p-CH3
p-H
p-F
p-Cl
p-CN
4H
64.9
65.2
65.8
65.9
66.6
67.9
70.1
70.2
70.5
70.6
71.0
71.5
30.9
31.0
31.3
31.3
31.7
32.4
9.1
9.0
9.0
8.9
9.2
9.1
0.337
0.348
0.361
0.365
0.375
0.401
-1.363
-1.355
-1.341
-1.339
-1.329
-1.295
p-CH3O
p-CH3
p-H
p-F
p-CN
69.7
70.1
70.5
70.6
72.6
70.9
71.1
71.4
71.4
72.6
34.1
34.2
34.3
34.4
35.5
8.3
8.3
8.3
8.2
8.5
0.407
0.418
0.431
0.434
0.471
-1.187
-1.181
-1.176
-1.172
-1.139
5H
p-CH3O
p-CH3
p-H
p-F
p-Cl
p-CN
6H
7H
8H
70.2
70.6
71.3
71.4
72.4
73.9
67.5
63.8
65.9
53.0
48.0
61.5
68.2
68.8
67.3
71.5
71.8
72.2
72.2
72.9
73.8
72.5
71.3
70.6
64.1
60.6
68.9
73.9
68.5
67.0
33.5
33.7
34.0
34.0
34.8
35.7
32.7
33.0
33.7
26.5
23.9
32.0
33.4
34.9
36.0
7.9
7.9
7.9
7.8
8.3
0.454
0.464
0.479
0.484
0.495
0.521
0.370
0.199
0.259
0.014
-0.094
0.142
0.370
0.332
0.222
-1.195
-1.187
-1.175
-1.171
-1.159
-1.131
-1.352
-1.463
-1.340
-1.618
-1.682
-1.458
-1.386
-1.125
-1.125
8.5
10.7
13.5
11.4
10.6
9.5
12.4
12.2
7.7
9H
10H
11H
12H
13H
14H
15H (R ))
CH3
Et
pr
i-pr
n-butyl
16H
17H
8.7
60.7
61.5
60.8
61.3
61.4
75.8
73.9
68.4
69.4
68.5
69.3
68.9
72.6
69.0
31.3
32.1
31.5
31.6
31.9
41.5
44.9
12.0
13.1
12.1
12.6
12.5
11.4
12.5
0.136
0.136
0.136
0.150
0.140
0.348
0.115
-1.470
-1.480
-1.468
-1.484
-1.464
-1.000
-0.924
a ∆HH D(XH) values were derived from eq 4, taking ∆HH A(PhXn+) ) 96.8 kcal/mol in acetonitrile from ref 40 the uncertainties are all
-
-
smaller than 1 kcal mol-1 b ∆HHD(XH), ∆HPD(XH•+), and ∆HHD(XH•+) were estimated from eqs 5-7, respectively, taking Eo(H+/0) ) -2.307
.
(V versus Fc+/0), Eo(H0/-) ) -1.137 (V versus Fc+/0), which was derived from Parker’s work42 adjusted to versus Fc+/0 by adding -0.537 V.
Relative uncertainties were estimated to be smaller than or close to 1 kcal/mol in each case. c The standard oxidation potential values of XH
and X• in acetonitrile were all derived from the experimental results by using OSWV method, because OSWV has been verified to be a more
exact electrochemical method for evaluating the standard one-electron redox potentials of analyte with irreversible electrochemical processes
than CV.9f,43
5-741 were formed according to Hess’ law, respectively. In eqs
not difficult to obtain the enthalpy change of XH to release
hydrogen atoms, the enthalpy changes of XH•+ to release
protons and to release hydrogen atoms in acetonitrile, if only
-
5-7, ∆HH D(XH) and ∆HHD(XH) are the enthalpy changes of
XH to release hydride anions and to release hydrogen atoms in
acetonitrile, respectively; the ∆HPD(XH•+) and ∆HHD(XH•+) are
the enthalpy changes of XH•+ to release protons and to release
hydrogen atoms in acetonitrile, respectively; Eo(X+/0), Eo(XH+/0),
Eo(H0/-), and Eo(H+/0) are the standard redox potentials of X+,
XH, H+, and H- in acetonitrile, respectively. Evidently, it is
∆HH D(XH), Eo(X+/0), Eo(XH+/0), Eo(H0/-), and Eo(H+/0) are
-
-
available. In fact, ∆HH D(XH) can be available from the above
work (Table 1), the standard redox potentials of Eo(H0/-) and
Eo(H+/0) can be obtained from the literature,42 and Eo(X+/0) and
Eo(XH+/0) can be obtained from experimental measurements

2062 J. Phys. Chem. B, Vol. 114, No. 5, 2010
Zhu et al.
TABLE 3: Dependence of the Hydride Transfer Rates from
SCHEME 3: Three Thermodynamic Cycles Constructed
on the Basis of the Chemical Process of XH to Release
Hydride Anion in Acetonitrile
XH to AcrH+ClO4 in Acetonitrile on the Reaction
-
Temperature
a
k2 (M-1 s1-
)
dihydropyridines 298 K
303 K
308 K
313 K
318 K
1H
p-CH3O
p-CH3
p-H
p-F
p-Cl
97.0
83.6
76.1
71.6
51.6
25.8
109.3
125.7
108.2
101.0
91.7
69.4
31.1
147.2
170.4
93.5
86.7
83.2
61.5
27.6
133.3
117.5
101.6
78.4
150.0
135.7
118.3
89.3
p-CN
36.8
41.4
2H
p-CH3O
p-CH3
p-H
p-F
p-Cl
25.5
23.8
17.7
14.9
12.8
9.81
36.3
33.4
21.2
20.4
16.9
12.5
44.5
41.4
26.1
23.5
19.3
13.6
53.1
49.8
31.7
29.5
24.5
16.4
64.4
59.5
36.4
34.5
29.2
19.9
p-CN
(Table 1). The detailed values of ∆HHD(XH), ∆HPD(XH•+), and
∆HHD(XH•+) of the 45 dihydropyridine-type organic hydrides
in acetonitrile are also summarized in Table 2.
3H
p-CH3O
p-CH3
p-H
p-F
p-Cl
p-CN
4H
p-CH3O
p-CH3
p-H
41.8
38.0
31.0
24.5
21.7
9.91
51.3
49.7
36.9
32.4
27.4
13.8
66.0
61.2
46.4
38.4
32.6
17.4
75.3
70.3
54.9
46.2
39.0
21.9
87.5
82.4
66.1
54.5
45.8
27.3
∆HHD(XH) ) ∆HH D(XH) - F[Eoox(X•) - Eo(H0/-)]
-
(5)
0.842
0.771
0.597
0.518
0.238
0.999
0.867
0.752
0.649
0.315
1.20
1.36
1.12
1.09
0.896
0.501
1.66
1.23
1.32
1.10
0.602
0.982
0.919
0.774
0.406
∆HHD(XH•-) ) ∆HHD(XH) - F[Eoox(XH) - Eo(H+/0)]
p-F
p-CN
5H
(6)
p-CH3O
p-CH3
p-H
p-F
p-Cl
p-CN
6H
7H
8H
0.668
0.641
0.455
0.332
0.161
0.092
25.8
0.823
0.777
0.553
0.389
0.204
0.114
31.4
0.968
0.885
0.652
0.457
0.254
0.134
40.1
1.25
1.03
1.37
1.16
∆HHD(XH•+) ) ∆HH D(XH) - F[Eoox(XH) - Eo(H0/-)]
-
0.755
0.531
0.296
0.151
48.8
0.850
0.612
0.359
0.192
59.4
(7)
The kinetics of hydride transfer from XH to acridinium
-
perclorate (AcrH+ClO4 ), a well-known hydride acceptor, were
83.4
43.8
95.8
52.1
106.3
63.5
122.3
77.1
144.6
86.0
conveniently monitored with stopped-flow or general UV-vis
absorption spectra by following the time dependence of the
absorbance at λmax ) 415 nm for the AcrH+ClO4- with XH in
more than 20-fold excess (Figure 4). The pseudo-first-order rate
constants were calculated by Guggenheim’s method.44 The
second-order rate constant (k2) at different temperature between
298 and 318 K are given in Table 3, which were derived from
plots of the pseudo-first-order rate constants versus the con-
centrations of XH. Eyring activation parameters, activation
9H
1.90 × 104 2.36 × 104 2.79 × 104 3.38 × 104 3.96 × 104
10H
11H
12H
13H
14H
15H
CH3
Et
pr
i-pr
n-butyl
2.61 × 104 3.17 × 104 3.77 × 104 4.45 × 104 5.10 × 104
91.3
1.65
4.62
3.63
107.1
1.88
5.53
4.22
125.7
2.28
6.30
4.49
149.2
2.73
7.18
5.18
171.3
3.35
7.68
5.66
288
238
281
102
343
0.52
3.02
347
303
352
130
415
0.62
3.28
388
357
387
150
472
0.74
3.47
463
423
444
175
576
0.86
3.75
514
477
511
204
656
1.03
3.97
16H
17H
a Second-order rate constants k2 were obtained from the
corresponding pseuso-first-order rate constants by the linear
correlation against the concentration of the XH, the experimental
error is within 5%.
enthalpy (∆H*) and activation entropy (∆S*), for the hydride
-
transfer from XH to AcrH+ClO4 are summarized in Table 4;
they were derived from Eyring plots of ln(k2/T) versus the
reciprocal of the absolute temperature (1/T), respectively.
Discussion
Thermodynamic Driving Force Scale of the Dihydropy-
ridine-Type Organic Hydrides (XH) To Release Hydride
Anions in Acetonitrile. It is well-known that the standard-state
enthalpy change of XH to release hydride anions is a very
important thermodynamic parameter of XH, which can be used
to scale the power of XH to donate hydride anions. From Table
2, it is found that the enthalpy changes of the 45 XH in
Figure 4. UV-vis spectra change obtained from the reaction of 4H
(2 mM) with AcrH+ClO4 (0.1 mM) in dry acetonitrile at 298 K at 3
-
min intervals (going downward). Inset: the time-resolved spectrum at
λmax ) 415 nm.

Dihydropyridine-Type Compounds as Hydride Source
J. Phys. Chem. B, Vol. 114, No. 5, 2010 2063
TABLE 4: Comparison of Activation Parameters of Hydride Transfer from XH to AcrH+ and Thermodynamic Driving Forces
of XH to Release Hydride Anions in Acetonitrile
∆HH T(XH)a
∆Hq(H-T)b
∆Sq(H-T)c
-T∆Sq(H-T)d
∆Gq(H-T)e
-
dihydropyridines
1H
p-CH3O
p-CH3
p-H
63.1
63.6
64.2
64.3
65.0
66.3
4.8
5.1
4.9
3.9
4.4
4.0
-33.6
-32.6
-33.6
-36.9
-35.8
-38.7
10.0
9.7
10.0
11.0
10.7
11.5
14.8
14.8
14.9
14.9
15.1
15.6
p-F
p-Cl
p-CN
2H
p-CH3O
p-CH3
p-H
66.2
66.5
67.1
67.2
67.6
69.0
7.8
7.8
6.3
7.1
7.0
5.8
-25.8
-25.9
-31.6
-29.2
-30.0
-34.7
7.7
7.7
9.4
8.7
9.0
15.5
15.5
15.8
15.8
15.9
16.1
p-F
p-Cl
p-CN
3H
10.3
p-CH3O
p-CH3
p-H
64.9
65.2
65.8
65.9
66.6
67.9
6.4
6.6
6.6
6.8
6.3
8.8
-29.6
-29.3
-29.7
-29.4
-31.1
-24.6
8.8
8.7
8.8
8.8
9.3
7.3
15.2
15.3
15.4
15.5
15.6
16.1
p-F
p-Cl
p-CN
4H
p-CH3O
p-CH3
p-H
p-F
p-CN
5H
69.7
70.1
70.5
70.6
72.6
5.7
3.9
6.8
6.3
8.1
-39.9
-46.2
-36.9
-38.7
-34.1
11.9
13.8
11.0
11.5
10.2
17.6
17.6
17.8
17.8
18.3
p-CH3O
p-CH3
p-H
70.2
70.6
71.3
71.4
72.4
73.9
67.5
63.8
65.9
53.0
48.0
61.5
68.2
68.8
67.3
6.4
4.9
5.3
5.2
6.9
6.0
7.4
4.5
6.0
6.2
5.7
5.4
6.1
5.8
3.9
-37.9
-43.1
-42.4
-43.4
-39.1
-43.3
-27.5
-34.9
-31.1
-18.2
-19.2
-31.6
-37.1
-36.2
-41.9
11.3
12.8
12.6
12.9
11.7
12.9
8.2
10.4
9.3
5.4
5.7
9.4
11.1
10.8
12.5
17.7
17.7
17.9
18.1
18.5
18.9
15.9
14.8
15.2
11.6
11.5
14.8
17.2
16.6
16.4
p-F
p-Cl
p-CN
6H
7H
8H
9H
10H
11H
12H
13H
14H
15H
CH3
Et
pr
i-pr
n-butyl
16H
17H
60.7
61.5
60.8
61.3
61.4
75.8
73.9
4.8
5.9
4.8
5.8
5.5
5.8
2.0
-31.0
-27.8
-31.2
-30.0
-28.5
-40.6
-49.8
9.2
8.3
9.3
8.9
8.5
14.1
14.2
14.1
14.7
14.0
17.9
16.8
12.1
14.8
a ∆HH D(XH) is enthalpy change of XH to release hydride anion in acetonitrile, the unit is kcal mol-1
.
b From the slope of the Eyring plots,
-
the unit is kcal mol-1
. . .
c From the intercept of the Eyring plot; the unit is cal mol-1 K-1 d The unit is kcal mol-1 e From the equation ∆Gq )
∆Hq - T∆Sq, the unit is kcal mol-1
.
acetonitrile range from 48.0 kcal/mol for 10H to 75.8 kcal/mol
for 16H. Because the enthalpy changes of the 45 XH in
acetonitrile all are not quite large, generally much smaller than
that of toluene in acetonitrile (118.0 kcal/mol),45 the dihydripy-
ridine-type organic hydrides XH especially with strongly
electron-donating groups should belong to good hydride donors,
which indicates that the 45 dihydripyridine-type organic hydrides
XH can construct a very useful organic hydrides library whose
thermodynamic driving forces all are available, and from this
organic hydrides library chemists can choose an organic hydride
donor as the suitable organic reducing agent for organic
syntheses. In the organic hydrides library, 10H is the strongest
organic hydride donor, the power to donate hydrides is close to
or even larger than those of some metal hydrides in acetonitrile,
such as HCo(dppe)2 (49.1 kcal/mol),46 [HNi(dmpe)2]+ (51 kcal
mol-1),46 CpMoH(PMe3)(CO)2 (55 kcal mol-1),47 CpMoH-
(PMe3)(CO)2 (58 kcal mol-1),47 [HCo(dppe)2]+ (59.7 kcal mol-1
kcal mol-1),48 [H2Co(dppe)2]+ (60 kcal/mol),48 [HNi(dmpp)2]+
(65.1 kcal mol-1),46 and [HNi(depp)2]+ (67 kcal/mol).46 In order
to intuitively compare the powers of the dihydropyridine-type
organic hydrides to donate hydride anions and make chemists
easily choose suitable dihydropyridine-type organic hydrides as
reducing agents, the 19 typical dihydripyridine-type organic

2064 J. Phys. Chem. B, Vol. 114, No. 5, 2010
Zhu et al.
Figure 5. Comparison of thermodynamic driving forces of some typical dihydropyridine-type organic hydrides (XH) to release hydride anions in
acetonitrile.
hydrides were ranked together according to their enthalpy
change values to release hydride anions in acetonitrile (Figure
5).
1H is larger than that of 16H by 11.6 kcal mol-1; i.e., the merger
of benzene unit into the pyridine ring can decrease the hydride-
donating ability of the dihydropyridine by 11.6 kcal mol-1
.
From Figure 5, it is found that the hydride-donating ability
of the dihydropyridine-type organic hydrides is not only
dependent on the nature and number of the substituents on the
dihydropyridine ring but also dependent on the aromaticity of
the dihydropyridine system as well as on the structure of
dihydropyridines. If the enthalpy change values of the dihy-
dropyridine-type organic hydrides 1H-10H are examined, it is
found that electron-donating groups, such as methyl and
methoxyl groups, can significantly increase the hydride-donating
ability; but electron-withdrawing groups, such as CN and CHO,
decrease the hydride-donating ability, and the contribution order
of the substituents to the hydride-donating ability of the
dihydropyridine-type organic hydrides is CH3 > H > CONHEt
> CONH2 > CO2Et > CONHPh > COCH3 > COOH > CHO >
CN. If the hydride-donating abilities of 13H and 14H are
compared, it is found that the hydride-donating ability of 1,2-
dihydropridine is larger than that of the corresponding 1,4-
dihydropridine by 1.5 kcal mol-1, which means that the state
free energy of the 1,2-dihydropyridine is higher than that of
the corresponding 1,4-dihydropyridine by 1.5 kcal mol-1. The
reason could be that the intramolecular tension of the 1,2-
dihydropyridine is larger than that of the corresponding 1,4-
dihydropyridine, which makes the hydrogen atom at the
2-position in the 1,2-dihydropyridine to be easier to escape as
hydride anions. If the hydride-donating abilities of 1H and 16H
are compared, it is found that the hydride-donating abilities of
In order to dig up the root resulting in the good hydride-
donating abilities of the dihydropyridine-type organic hydrides,
the product structure of the dihydropyridine-type organic
hydrides to release hydride anions is examined. From eq 1, it
is found that the process of 9H to release hydride anions does
not only involve the dissociation of one old C-H bond to
consume energy but also involves the formation of one new
CdN π-bond to release energy; i.e., the magnitude of enthalpy
change values of the dihydropyridine-type organic hydrides to
release hydride anions should be equal to the heterolytic
dissociation energy of the old C-H σ-bond minus the heterolytic
dissociation energy of the CdN π-bond newly formed. Thus,
it is easy to understand why the powers of the dihydropyridine-
type organic hydrides to release hydride anions in acetonitrile
are generally quite large, the reason is that, during the hydride
transfer from the organic hydrides, formation of new CdN
π-bond on the pyridine ring can release energy to promote the
hydride anions to leave.
In order to quantitatively examine the contribution of the
formed π-bond in the product to the hydride-donating abilities
of the organic hydrides, the thermodynamic driving forces of
9H and toluene49 to release hydride anions in acetonitrile are
compared (see eqs 8 and 9). From eqs 8 and 9, it is found that
the hydride-donating abilities of 9H (53.0 kcal/mol) are larger
than that of toluene in acetonitrile (118.0 kcal/mol)45 by 65.0
kcal mol-1. Since 65.0 kcal/mol is smaller than the heterolytic

Dihydropyridine-Type Compounds as Hydride Source
J. Phys. Chem. B, Vol. 114, No. 5, 2010 2065
dissociation energies of CdN π-bonds of some neutral pyridine
derivatives (80 kcal mol-1),50 it is clear that the contribution of
the resonance structure II of 9+ to the natural structure of 9+
could not be 100%,51 which means that the contribution of the
resonance structure I to the natural structure of 9+ can not be
neglected. According to the heterolytic dissociation energy of
CdN π-bond in acetonitrile solution (80 kcal mol-1),50 and the
difference of the hydride-donating abilities between 9H and
toluene in acetonitrile, the contribution of resonance structures
II and I to the natural structure of 9+ can be estimated; the result
is 81.2% and 18.8% from the resonance structures II and I,
respectively, which means that the natural structure of 9+ should
resemble the idealized Lewis-type resonance structure with the
three π-bonds on the pyridine ring (II) much more than the
resonance structure I. This result suggests that 9+ should be a
stable chemical species, because the chemical bonds for all
atoms in the resonance structure II of 9+ are sufficient. As for
the dihydropyridines 1H and 16H, the contribution of the
resonance structure II of 1+ to the natural structure of 1+ and
the contribution of the resonance structure II of 16+ to the natural
structure of 16+ can be estimated by using the same method as
described above; the result is 67.4% (eq 10) and 52.7% (eq
11), respectively. Since the contribution of the resonance
structure II of 1+ to the natural structure of 1+ is larger than
that of the resonance structure II of 16+ to the natural structure
of 16+ by about 14.4%,52 it is not difficult to understand why
the hydride-donating ability of 1H is larger than that of 16H
by 11.6 kcal/mol.
Figure 6. Comparison of thermodynamic driving forces of some typical
dihydropyridine-type organic hydrides (XH) to release a hydrogen atom
in acetonitrile.
organic hydrides XH to release hydrogen atoms in acetonitrile
range from 60.6 kcal mol-1 for 10H to 73.9 kcal mol-1 for 12H.
Since the enthalpy change values of the 45 XH all are
significantly lower than that of vitamin E (79.3 kcal mol-1),53
the 45 dihydropyridine-type organic hydrides all belong to good
hydrogen atom donors, which means that the 45 organic
hydrides all can be used as good antioxidants to quench some
well-known radicals, such as O• (102.8 kcal mol-1),54 HO• (118.8
kcal mol-1),54 HOO• (87.8 kcal mol-1),55 i-C3H7OO• (85.1 kcal
mol-1),56 PhS• (83.5 kcal mol-1),57 RSS• (70.0 kcal mol-1),58
and TEMPO• (71.2 kcal mol-1).59 But for the radical of O2 (48.2
•
kcal mol-1),60 the 45 dihydropyridine-type organic hydrides all
have no work to quench it. In order to more intuitively compare
the powers of the organic hydrides to donate hydrogen atoms
and make one easily choose the dihydropyridine-type organic
hydrides as suitable antioxidants, 19 typical dihydropyridine-
type organic hydrides were ranked in order according to the
values of the enthalpy changes in acetonitrile (Figure 6). From
Figure 6, it is found that the substituent at the pyridine ring has
evident effect on the hydrogen-atom-donating ability of the
organic hydrides and generally, the electron-drawing groups,
such as cyano, can decrease the hydrogen-donating ability, but
electron-donating groups, such as methyl, can increase the
hydrogen-donating ability, which suggests that the neutral
pyridine-type radicals X• should be due to electron-deficient
radicals.
In order to examine the actual structure of X•, the
thermodynamic driving forces of 9H and toluene to release
hydrogen atoms in acetonitrile are compared (see eqs 12 and
13). From eqs 12 and 13, it is found that the hydrogen-atom-
Thermodynamic Driving Forces of the Dihydropyridine-
type Organic Hydrides (XH) To Release Hydrogen Atoms
in Acetonitrile. From the second column in Table 2, it is clear
that the enthalpy change scales of the 45 dihydropyridine-type
donating ability of 9H (64.1 kcal mol-1) is larger than that
of toluene in acetonitrile (90.1 kcal mol-1
)
by 26.0 kcal
48
mol-1. Since the homolytic dissociation energy of CdN

2066 J. Phys. Chem. B, Vol. 114, No. 5, 2010
Zhu et al.
π-bond on the neutral pyridine ring has been estimated to
radical cations of the dihydropyridine-type organic hydrides
XH•+ can not only quench some very active radicals, such as
O•, HO•, and HOO•, but also quench the relative stable radicals,
be about 66 kcal mol-1 50
the contribution of resonance
,
structures II and I to the actual structure of 9• can be estimated
according to the difference between the enthalpy change of
9H to release hydrogen atoms (64.1 kcal mol-1) and the
homolytic dissociation energy of CdN π-bond (66 kcal
mol-1); the result is 39.4% and 60.6% for the resonance
structures II and I, respectively, which means that the actual
structure of 9• should resemble the idealized Lewis-type
resonance structure I with two π-bonds on the pyridine ring
rather than the idealized Lewis-type resonance structure II
with three π-bonds on the pyridine ring, which means that
9• should primarily belongs to carbon radical rather than
nitrogen radical. Since the carbon atom at 4-position in the
resonance structure I is lacking a chemical bond, 9• should
be a very active radical, but the activity should be markedly
smaller than that of the benzyl radical, because the contribu-
tion of the resonance structure I to the actual structure of 9•
is merely 60.6%.
•
such as O2 , NO•, and ONNOH• by hydrogen atom transfer. This
result suggests that the radical cations of the dihydropyridine-
type organic hydrides XH•+ all are unstable in the air.
According to the values of the enthalpy changes for the 45
XH•+ to release protons (7.7-13.5 kcal mol-1), it is clear that
the dihydropyridine-type radical cations (XH•+) belong to strong
proton donors, the acidities of them in acetonitrile are much
greater than those of some typical organic acids in acetonitrile,
such as benzoic acid (pKa ) 20.1, equivalent to 27.5 kcal mol-1
free energy change of benzoic acid to release proton)61 and
trifluoroacetic acid (pKa ) 12.7, equivalent to 17.4 kcal mol-1
free energy change of trifluoroacetic acid to release proton in
acetonitrile),62 but smaller than of some inorganic acids in
acetonitrile, such as HBr (pKa ) 5.5, equivalent to 7.5 kcal
mol-1 free energy change of HBr to release proton in acetoni-
trile),63 and HCl (pKa ) 8.9, equivalent to 12.2 kcal mol-1 free
energy change of HCl to release proton in acetonitrile),63 and
H2S (pKa ) 0.5, equivalent to 0.7 kcal mol-1 free energy change
of H2S to release proton in acetonitrile).64
In order to more intuitively compare the thermodynamic
driving forces of the radical cations to release hydrogen atoms
and to release protons as well as to more conveniently examine
the effect of substituents at the pyridine ring on the thermody-
namic driving forces of the radical cations to release hydrogen
atoms and to release protons, the 19 typical radical cations of
the XH are ranked in Figures 7 and 8 according to their
corresponding values of the enthalpy changes in acetonitrile,
respectively. From Figures 7 and 8, it is found that, although
the substituents at the dihydropyridine ring have significant
effect on the thermodynamic driving forces of the radical cations
to release hydrogen atoms and to release protons, no well linear
relationship can be found; the reason could be that the
mechanism of the substituents effect on the thermodynamic
driving forces of the radical cations to release hydrogen atoms
and to release protons is quite complicated.
Since the enthalpy change values of the 45 XH•+ to release
protons and to release hydrogen atoms all are quite larger than
zero, it is conceived that the radical cations XH•+ in acetonitrile
should be relatively stable, which means that XH•+ in anaerobic
acetonitrile solution all could be directly detected and character-
ized by EPR spectroscopy under general experimental condi-
tions.65,66 Since the proton-donating ability of XH•+ is much
larger than the corresponding hydrogen-atom-donating ability,
it is conceivable that when the hydride transfer from the
dihydropyridine-type organic hydrides were initiated by electron
transfer, the possibility of proton transfer in the second reaction
step should be much larger than that of the hydrogen atom
transfer in the second reaction step. That is, the e-H+-e
sequence hydride transfer should be most likely among the
various possible multistep mechanisms for the hydride transfer
from the dihydropyridine-type organic hydrides (Scheme 1), if
the hydride transfer were initiated by single-electron transfer.
Thermodynamic Driving Forces of Radical Cations of
the Dihydropyridine-Type Organic Hydrides (XH•+) To
Release Hydrogen Atoms and To Release Protons in Aceto-
nitrile. As is well-known, radical cations of organic hydrides
(XH•+) are one of the most important reaction intermediates of
the organic hydrides as organic reducing agents, when the
hydride transfer is initiated by electron transfer. Since the
enthalpy changes of the radical cations to release hydrogen
atoms and protons can not only be used to quantitatively scale
the characteristic chemical properties of the radical cations but
also to diagnose the mechanism of the hydride transfer from
the organic hydrides, it is necessary to examine and compare
the enthalpy changes of the radical cations to release hydrogen
atoms and to release protons. From columns 4 and 5 in Table
2, we found that the enthalpy change scales of the 45 XH•+ to
release hydrogen atoms and to release protons range from 23.9
to 44.9 kcal mol-1 and from 7.7 to 13.5 kcal mol-1, respectively.
According to the enthalpy change values of the 45 XH•+ to
release hydrogen atoms (23.9-44.9 kcal/mol), it is conceived
that the radical cations of the dihydropyridine-type organic
hydrides should be very strong hydrogen atom donors, and the
hydrogen-atom-donating abilities of the 45 XH•+ all are larger
than that of the well-known HOO•, a very strong hydrogen atom
donor in acetonitrile (48.2 kcal mol-1),58 which means that the
Thermodynamic Driving Forces of the Dihydropyridine-
Type Organic Hydrides (XH) and Their Neutral Pyridine-
Type Radicals (X•) To Release Electrons in Acetonitrile. As
is well-known, the standard oxidation potentials of the dihy-
dropyridine-type organic hydrides (XH) and their neutral
pyridine-type radicals (X•) are very important electrochemical
parameters, which can be used as an indicator of the electron-
donating ability of XH and X• in solution.

Dihydropyridine-Type Compounds as Hydride Source
J. Phys. Chem. B, Vol. 114, No. 5, 2010 2067
Figure 7. Comparison of thermodynamic driving forces of the corresponding radical cations (XH•+) of some typical dihydropyridine-type organic
hydrides to release a hydrogen atom in acetonitrile.
From column 6 in Table 2, it is found that the one-electron
oxidation potentials of XH [Eo(XH0/-)] range from -0.094 (V
vs Fc+/0) for 10H to 0.521 (V vs Fc+/0) for 5H (G ) p-CN).
Since the one-electron oxidation potentials of the 45 XH all
are not quite negative (generally positive than that of ferrocene),
which means that the 45 XH all are quite weak one-electron
donors. In order to intuitively compare the electron-donating
abilities among the dihydropyridine-type organic hydrides and
conveniently examine the effect of the substituents and the
structure of the organic hydrides on the electron-donating ability,
19 typical dihydripyridine-type organic hydrides are ranked in
Figure 9 according to their oxidation potentials. From Figure
9, it is clear that the electron-donating group (EDG) at the
pyridine ring can increase the electron-donating ability of the
organic hydrides, and the electron-withdrawing group (EWG)
at the pyridine ring can decrease the electron-donating ability
of the organic hydrides, but no good linear relationships were
found between the oxidation potentials and the well-known
substituent parameters, such as σ, σo, σ+, σ-. If the oxidation
potentials of 1H-10H were compared in detail, it is found that
the contribution order of the substituents to the electron-donating
ability of the organic hydrides is CH3 > H > CONHEt > CONH2
> CONHPh > COCH3 > CO2Et > COOH > CHO > CN. It is
worth noteing that if the substituent effects on the electron-
donating abilities and on the hydride-donating abilities are
compared, it is found that the contribution orders of the
substituents to the electron-donating ability all are not in
agreement with that of the substituents to the hydride-donating
ability. The difference appears in the cases of two substituents
-COCH3 in 2H and -COOEt in 3H. To the hydride-donating
ability, the contribution of -COCH3 (67.1 kcal mol-1 for 2H)
is smaller than that of -COOEt (65.8 kcal mol-1 for 3H), but
to the electron-donating ability, the contribution of -COCH3
(0.323 V for 2H) is larger than that of -COOEt (0.361 V for
3H). This result suggests that 2H and 3H can be used together
as mechanism probes to diagnose the mechanism details of
quinone reduction by some organic hydrides, which have been
disputed until now.
From column 7 in Table 2, it is found that the one-electron
oxidation potentials of the neutral pyridine-type radicals X•
[Eoox(X)] range from -0.924 (V vs Fc+/0) for 17• to -1.682 (V
vs Fc+/0) for 10•. Since the one-electron oxidation potentials of
X• are quite negative values, generally more negative than
-0.924 V relative to ferrocene, the neutral pyridine-type radicals
(X•), especially attached by electron-donating groups should
belong to very strong one-electron donors. Since the oxidation
potentials of X• are close to or even more negative than the
reduction potential of molecular oxygen (O2) (-1.050 V vs Fc+/0
saturated in acetonitrile, about 3 × 10-3 M),67 a valuable
conclusion can be made that the neutral pyridine radicals (X•)
are impossible to exist stably in living body or in oxygenic
solution. This result indicates that if we want to detect the neutral
pyridine-type radicals X• during the reactions of some dihy-
dropyridine-type organic hydrides, the oxygen must be removed
completely from the reaction system. In order to more intuitively
disclose the effect of structure and substituents on the electron-

2068 J. Phys. Chem. B, Vol. 114, No. 5, 2010
Zhu et al.
Figure 8. Comparison of thermodynamic driving forces of the corresponding radical cations (XH•+) of some typical dihydropyridine-type organic
hydrides to release a proton in acetonitrile.
donating abilities of X•, the typical X• (1-17, G ) H) are ranked
in Figure 10 according to their one-electron oxidation potentials.
From Figure 10, there are two orders to be found: (i) the
electron-withdrawing abilities of the substituents at the pyridine
ring of X• are increased in the order CH3, < H < CONHEt <
CONH2 < COOH < COOEt < CONHPh < COCH3 < CHO <
CN; (ii) the larger the aromaticity of X•, the smaller the electron-
donating ability of X•.
potentials between X• and XH (1H-15H) is quite small, but
the effect of framework structure on the difference of the
oxidation potentials between X• and XH is quite marked (see
16H and 17H). Generally, the larger the aromaticity of the
structure, the smaller the difference of oxidation potentials
between X• and XH.
If the oxidation potentials of the neutral pyridine-type radicals
(X•) and their parent dihydropyridine-type organic hydrides
(XH) were compared, it is found that the oxidation potentials
of X• are more negative than that of the corresponding parent
XH by more than 1.0 V (generally 1.0-1.7 V), which indicates
that the electron-donating ability of X• is much larger than that
of the corresponding parent XH. In order to examine the factor
which makes the electron-donating ability of X• is larger than
that of XH, the structures of XH and XH•+ (eq 14) as well as
the structures of X• and X+ (eq 15) were compared. From eq
14, it is clear that the oxidation of XH deals only with an
electron escape from XH, since no new π-bond was formed in
the molecule, but for the oxidation of X• (eq 15), the oxidation
of X• deals not only with an electron escape from X•, but also
with the formation of a new π-bond in the pyridine ring. Since
the formation of the new π-bond can release a large amount of
energy, the electron-donating ability of X• should be much larger
than that of XH.
Construction of the Thermodynamic Characteristic Graphs
(TCGs) of Dihydropyridines as a “Molecule ID Card”. It is
well-known that the structure of the organic hydride compounds
(such as a dihydropyridine) can be safely diagnosed or
determined according to its some characteristic spectra, such
If the effects of structure and substituent on the differences
of oxidation potentials between X• and XH are examined, it is
found that the substituent effect on the difference of oxidation

Dihydropyridine-Type Compounds as Hydride Source
J. Phys. Chem. B, Vol. 114, No. 5, 2010 2069
Figure 9. Comparison of thermodynamic driving forces of some typical dihydropyridine-type organic hydrides (XH) to release an electron in
acetonitrile.
as NMR spectrum, IR spectrum, and MS. But the chemical
properties of the organic hydride and its various reaction
intermediates could not be directly diagnosed or determined only
according to a certain spectrum or graph of the molecule until
now. If a certain characteristic chemical information graph of
molecule can be produced, and can be efficiently used to
quantitatively diagnose or scale the characteristic chemical
properties of the molecule and its various reaction intermediates,
which is the case that the NMR spectrum and IR spectrum of
molecule can be used to determine the molecular structure, the
chemists’ dream for a long time could become reality that only
from the characteristic graphs of molecules one could reliably
design various new desired chemical reactions, safely predict
the possible products of reactions, and exactly parse the reaction
mechanism. Therefore, developing a characteristic graph of
molecule as a “Molecule ID Card”, which contains the essential
information about the chemical properties of molecules and their
various reaction intermediates has been my ambition for a long
time.
In Table 2, it is found that there are six primary thermody-
namic parameters about the characteristic chemical or electro-
chemical properties of the dihydropyridines (XH) and their
reaction intermediates (XH•+ and X• and X+), which have been
obtained by using the experimental method in this work. Since
the sizes of proton, hydride anion, hydrogen atom, and electron
are all quite small, it is conceived that the thermodynamic
driving forces of the dihydropyridines and their various reaction
intermediates to release hydride anions, hydrogen atoms,
protons, and electrons should be the most intrinsic thermody-
namic parameters to quantitatively scale the characteristic
chemical properties of the dihydropyridines and their reaction
intermediates, such as oxidizability, reducibility, antioxidants,
hydricity, acidity, nucleophilicity, electrophilicity, and so on,
which gives us one efficient access to quantitatively scale the
chemical properties of dihydropyridines and especially their
reaction intermediates. If the six thermodynamic parameters
scaling the different chemical characters of dihydropyridines
and their reaction intermediates are gathered together according
to their mutual conversion to build a graph, it is clear that, for
any species among the dihydropyridines and their various
reaction intermediates, one can obtain three characteristic
thermodynamic parameters from the graph to quantitatively
diagnose the characteristic chemical properties of the species.
Since this graph consists only of thermodynamic parameters of
dihydropyridines and their reaction intermediates, this graph in
this work is defined as the thermodynamic characteristic graph
(TCG) of the dihydropyridines (XH), which can be used as a
“Molecule ID Card” to quantitatively diagnose the characteristic
chemical properties of the dihydropyridines and their reaction
intermediates in acetonitrile solution.
Scheme 4 shows the thermodynamic characteristic graphs
(TCG) of dihydropyridine 9H as an example. It is clear that
from the TCG of 9H, three thermodynamic characteristic
parameters can be obtained for each species among the species
system of 9H (including 9H, 9H•+, 9•, and 9+) (see Table 5).
The three different thermodynamic parameters can be used to
quantitatively describe three different characteristic chemical
properties of the species at the same time. From Table 5, it is
easy to make a diagnosis that 9H is good hydride donor, the
radical cation of 9H is a good oxidant and a strong organic

2070 J. Phys. Chem. B, Vol. 114, No. 5, 2010
Zhu et al.
Figure 10. Comparison of thermodynamic driving forces of the corresponding pyridine-type neutral radicals (X•) of some typical dihydropyridine-
type organic hydrides to release an electron in acetonitrile.
SCHEME 4: Thermodynamic Characteristic Graph
(TCG) of Dihydropyridine 9H as a “Molecule ID Card”
applied in the diagnoses of the characteristic chemical properties
of imines and their various reaction intermediates in our previous
paper.50
Relationship between Thermodynamics and Kinetics for
the Hydride Transfer from XH to AcrH+. In principle,
thermodynamic driving forces of XH to release hydride anions
are only used to measure the tendency of hydride transfer from
XH, which cannot be directly used to predict the rate of the
hydride transfer. But, in fact, for most chemical reactions, the
reaction rate is directly related with thermodynamic driving
forces. In order to disclose the intrinsic relationship between
the kinetic rate of hydride transfer and the corresponding
thermodynamic driving force of hydride transfer, the dependence
of the logarithm of second-order rate constant (log k2) for
hydride transfer from XH to AcrH+ on the thermodynamic
driving force of XH to release hydride anions in acetonitrile
was examined, and the results show that, if the dihydropyridine-
type organic hydrides cover the 45 XH (1H-17H), the linear
relationship is not good, which means that the kinetic rate of
acid, 9• is a strong reductant, and 9+ is a quite stable species.
Evidently, the thermodynamic characteristic graph (TCG) of a
hydride transfer is not only dependent on the corresponding
thermodynamic enthalpy change of hydride transfer but also
molecule is a very useful chemical information memorizer of
molecules, which not only can be used to diagnose the chemical
characters of the dihydropyridines and their various reaction
intermediates but also can be used to construct thermodynamic
analysis platform to predict reaction products and analyze the
reaction mechanism. In fact, this idea has been successfully
dependent on some other thermodynamic factors such as entropy
change of XH. However, when the dihydropyridine-type organic
hydrides are limited in 1H-15H except some ones with strong
electron-donating group on the pyridine ring, the linear relation-
ship is good (r ) 0.9673) (see Figure 11), which means that if
XH have the same or similar fundamental structure, log k2 of

Dihydropyridine-Type Compounds as Hydride Source
J. Phys. Chem. B, Vol. 114, No. 5, 2010 2071
TABLE 5: Chemical Properties of Dihydropyridine 9H and Its Various Reaction Intermediates Diagnosed According to the
TCG of 9H (Scheme 4)
* ∆HPA(9•), ∆HHA(9•), ∆HH A(9+), and ∆HHA(9+) are defined as the enthalpy changes of 9• to obtain proton, to obtain hydrogen atom, and
-
the enthalpy changes of 9+ to obtain hydride anion and to obtain hydrogen in acetonitrile, respectively. The values are equal to the enthalpy
changes of the corresponding opposite species to obtain proton, to obtain hydrogen atom and to obtain hydride anion in acetonitrile by
switching the signs.
SCHEME 5: Possible Reaction Pathways of Hydride
Transfer from Dihydropyridine-Type Organic Hydrides
(XH) to AcrH+ in Acetonitrile
still a disputed question.68,69 The focus of the controversy is
whether the mechanism of the hydride transfer is one step or
multistep sequence involving electron transfer as the initial step:
electron-proton-electron, electron-hydrogen, or hydrogen-
electron. One of the main reasons resulting in the difficulty to
elucidate the hydride transfer mechanism is that no detailed
energetic data of each possible mechanistic step for the hydride
transfer are available. From this work, we not only can obtain
the thermodynamic driving forces of the 45 dihydropyridine-
type organic hydrides to release hydride anion, hydrogen atom,
and electron but also can obtain the thermodynamic driving
forces of the various reaction intermediates of the 45 dihydro-
pyridine-type organic hydrides to release hydrogen atom, proton,
and electron. It is clear that according to these thermodynamic
data we may construct a thermodynamic analytic platform to
examine the detailed mechanistic steps of the hydride transfer.
Herein we take the reaction of XH and AcrH+ as an example
(see Scheme 5). The detailed thermodynamic data on the each
possible mechanistic step of the hydride transfer are summarized
in Table 6.
Figure 11. Relationship between log k2 (at 25 °C) for hydride transfer
from XH (1H-15H) to AcrH+ and the enthalpy changes of XH to
release hydride anions in acetonitrile.
the hydride transfer can be well dependent on the enthalpy
changes of XH to release hydride anions in acetonitrile and the
relationship can be expressed by eq 14. This finding suggests
that for any organic hydrides with the same or similar
fundamental structure, the rate of the hydride transfer may be
estimated according to the corresponding thermodynamic driving
forces.
log k2 ) -0.266 × ∆HH D(XH) + 18.76
(16)
-
Thermodynamic Analysis on Mechanism Possibilities
for the Hydride Transfer from XH to AcrH+. Although the
dihydropyridine-type organic hydrides all have quite good
hydride-donating abilities and the applications as organic hydride
donors have been extensively investigated, the hydride transfer
mechanism to two-electron acceptor (i.e., hydride acceptor) is
From Table 6, it is easy to find that the state energy change
scales of the three initial steps (steps a, b, and c) in the four

2072 J. Phys. Chem. B, Vol. 114, No. 5, 2010
Zhu et al.
TABLE 6: Energetics of Each Mechanistic Step of Hydride
Transfer from XH to AcrH+ Shown in Scheme 5
∆Ho (or ∆Go)
XH
step aa step bb step cc step dd step ee step ff
1H
p-CH3O
p-CH3
p-H
p-F
p-Cl
22.9
23.0
23.2
23.3
23.6
24.3
25.7
26.1
26.5
26.5
27.0
27.6
-18.0
-17.5
-16.9
-16.8
-16.1
-14.8
2.8
3.0
3.2
3.1
3.4
3.2
-40.8 -43.6
-40.5 -43.5
-40.1 -43.3
-40.1 -43.2
-39.7 -43.1
-39.1 -42.3
p-CN
2H
p-CH3O
p-CH3
p-H
25.1
25.3
25.6
25.7
26.1
26.7
26.4
26.5
26.9
26.9
27.0
27.8
-14.9
-14.6
-14.0
-13.9
-13.5
-12.1
1.3
1.1
1.2
1.1
0.9
1.0
-40.0 -41.3
-39.9 -41.0
-39.6 -40.8
-39.6 -40.7
-39.6 -40.5
-38.8 -39.8
p-F
p-Cl
p-CN
3H
Figure 12. Plots of ∆Gq (2), ∆Hq (9) and -T∆Sq (O) for hydride
p-CH3O
p-CH3
p-H
p-F
p-Cl
25.9
26.2
26.5
26.6
26.8
27.4
25.9
26.0
26.3
26.4
26.8
27.3
-16.2
-15.9
-15.3
-15.2
-14.5
-13.2
-0.1
-0.2
-0.2
-0.3
0
-42.1 -42.0
-42.0 -41.9
-41.7 -41.5
-41.7 -41.5
-41.3 -41.3
-40.6 -40.5
transfer from XH to AcrH+ in acetonitrile against ∆HH D(XH).
-
for the concerted hydride transfer (step c). Since the state energy
changes for the concerted hydride transfer (step c) all are quite
negative (more negative than -7.2 kcal mol-1), and the state
energy changes for the electron transfer and for hydrogen
transfer all are quite positive (more positive than 16.0 kcal
mol-1), it is reasonable to suggest that the electron transfer
process (step a) and the hydrogen transfer process (step b) all
can be ruled out as the initial step for the reaction of XH with
AcrH+, and as a result, the remaining concerted hydride transfer
step (step c) should be the merely reasonable pathway for the
reaction of XH with AcrH+.
In order to further verify the reaction mechanism of XH with
AcrH+, the kinetics of the reaction was examined. From Table
4, it is found that the activation free energetic scales of the
reactions of XH with AcrH+ range from 11.5 to 18.9 kcal mol-1,
which are much smaller than the corresponding standard state
energy changes of the initial electron transfer (step a) (16.0-30.2
kcal mol-1), and much smaller than the corresponding standard
state energy changes of the initial hydrogen transfer (step b)
(16.4-29.6 kcal mol-1), but larger than the corresponding
standard state energy change of the concerted hydride transfer
(step c) (-7.2 to -33.1 kcal mol-1). On the basis of a general
reaction law that the activation free energy change is always
larger than or at least equal to the corresponding standard state
free energy change for any elemental reaction,70 it is evident
that both of the reaction steps a and b should be ruled out as
the initial reaction in the reactions of XH with AcrH+, and the
only remaining step c is suitable for the reaction law (Figure
12).
p-CN
4H
p-CH3O
p-CH3
p-H
p-F
p-CN
5H
p-CH3O
p-CH3
p-H
p-F
p-Cl
p-CN
-0.1
27.5
27.8
28.1
28.2
29.0
26.7
26.9
27.2
27.2
28.4
-11.4
-11.0
-10.6
-10.5
-8.5
-0.9
-0.9
-0.9
-1.0
-0.7
-38.9 -38.0
-38.8 -37.8
-38.7 -37.7
-38.6 -37.6
-37.5 -36.9
28.6
28.8
29.2
29.3
29.6
30.2
26.7
22.7
24.1
18.5
16.0
21.4
26.7
25.8
23.3
27.3
27.6
28.0
28.0
28.7
29.6
28.3
27.1
26.4
19.9
16.4
24.7
29.7
24.3
22.8
-10.9
-10.5
-9.8
-1.3
-1.3
-1.3
-1.4
-0.9
-0.7
1.5
-39.5 -38.2
-39.3 -38.0
-39.0 -37.7
-39.0 -37.6
-38.2 -37.3
-37.3 -36.7
-40.3 -41.8
-40.0 -44.3
-39.3 -41.5
-46.5 -47.9
-49.1 -49.4
-41.0 -44.2
-39.6 -42.6
-38.1 -36.6
-37.0 -36.6
-9.7
-8.7
-7.2
6H
-13.6
-17.3
-15.2
-28.1
-33.1
-19.6
-12.9
-12.3
-13.8
7H
4.3
8H
2.2
9H
1.4
10H
11H
12H
13H
14H
15H
0.3
3.2
3.0
-1.5
-0.5
CH3
Et
pr
i-pr
n-butyl
16H
17H
21.3
21.3
21.3
21.6
21.4
26.2
20.8
24.2
25.2
24.3
25.1
24.7
25.3
24.8
-20.4
-19.6
-20.3
-19.8
-19.7
-8.4
2.8
3.9
-41.7 -44.5
-40.9 -44.7
-41.5 -44.5
-41.4 -44.8
-41.1 -44.4
-34.6 -33.7
-28.1 -31.9
2.9
3.4
3.3
-0.9
-7.2
3.3
a Derived from the equation ∆G(step a) ) -23.06[Ered(AcrH+) -
Eox(XH)], where [Ered(AcrH+) ) -0.787 V vs Fc,9f and the unit of
∆G(step a) is kcal mol-1 b Derived from the equation ∆H(step b) )
.
By comparing the values of ∆Hq and -T∆Sq, it is found that
the values of ∆Hq are generally much smaller than that of the
corresponding -T∆Sq, which means that the hydride transfer
from XH to AcrH+ is mainly driven by enthalpy change of the
reaction, and that is the reason that the kinetic rate of hydride
transfer from XH to AcrH+ is strongly dependent on the
corresponding thermodynamic driving forces of XH to release
hydride anion.
∆HHD(XH) - ∆HHD(AcrH2•+), where ∆HHD(AcrH2•+) ) 44.2 kcal
mol-1 9f and the unit of ∆H(step b) is kcal mol-1 c Derived from
the equation ∆H(step c) ) ∆HH-D(XH) - ∆HH-D(AcrH2), where
∆HH-D(AcrH2) ) 81.1 kcal mol-1 35
and the unit of ∆H(step c) is
kcal mol-1 d Derived from the equation ∆H(step d) ) ∆HPD(XH•+)
- ∆HPD(AcrH2•+), where ∆HPD(AcrH2•+) ) 9.2 kcal/mol,9f and the
unit of ∆H(step d) is kcal mol-1 e Derived from the equation
∆H(step e) ) ∆HHD(XH•+) - ∆HHD(AcrH2), where ∆HHD(AcrH2)
,
.
,
.
.
) 73.0 kcal mol-1 9f and the unit of ∆H(step e) is kcal mol-1
.
,
f Derived from the equation ∆G(step f) ) -23.06[Ered(AcrH2•+) -
Eox(X•)], where [Ered(AcrH2•+) ) 0.460 V vs Fc,9f and the unit of
Conclusions
∆G(step f) is kcal mol-1
.
In this work, 45 dihydropyridine-type organic compounds as
a class of very important organic hydride source were designed
and synthesized. The thermodynamic driving forces of the 45
organic hydrides to release hydride anions, to release hydrogen
atoms, and to release electrons, the thermodynamic driving
possible pathways range from 16.0 to 30.2 kcal mol-1 for the
electron transfer (step a), from 16.4 to 29.6 kcal/mol for the
hydrogen transfer (step b), and from -7.2 to -33.1 kcal/mol

Dihydropyridine-Type Compounds as Hydride Source
J. Phys. Chem. B, Vol. 114, No. 5, 2010 2073
the acidities are generally much greater than that of the general
neutral strong organic acids, but smaller than that of the gneral
strong inorganic acids in acetonitrile.
(5) The radical cations of the dihydropyridine-type organic
compounds all are strong hydrogen atom donors, and the
hydrogen-donating abilities are generally greater than those of
the corresponding parent XH by about 30-40 kcal/mol, but
generally smaller than the corresponding proton-donating abili-
ties by more than 20 kcal mol-1
.
(6) The pyridine-type neutral radicals (X•) all are very strong
one-electron donors, and the electron-donating abilities are
generally greater than those of the corresponding parent XH
by more than 1 V (equivalent to 23.06 kcal mol-1), which means
that when the dihydropyridine-type organic hydrides are chosen
as reducing agents to reduce organic unsaturated compounds,
such as ketone, aldehydes, and imines, the multistep mechanism
(e-p-e) of the hydride transfer is impossible to be separated.
(7) The reason resulting in the good hydricity of the
dihydropyridine-type compounds (XH) is that the carbon atom
at 4-position in the cation X+ can form or partially form a new
π-bond in the pyridine ring.
(8) The thermodynamic driving forces of the dihydropyridine-
type compounds to release hydride anions in acetonitrile were
found to be linearly well correlated with the rate of the hydride
transfer from the dihydropyridine-type organic compounds to
AcrH+.
Figure 13. Comparison of state energy changes for the three possible
initial steps of hydride transfer from N-benzyl-1,4-dihydropyridine (9H)
to AcrH+ and the activation free energy of the hydride transfer.
forces of the radical cations of the 45 dihydropyridines to release
protons and to release hydrogen atoms, and the thermodynamic
driving forces of the neutral pyridine-type radicals to release
electrons in acetonitrile were determined by using titration
calorimetry and electrochemical methods. After detailed ex-
amination of the dependence of the thermodynamic driving
forces on the structure of the dihydropyridines, the dependence
of the thermodynamic driving forces on the kinetics of the
hydride transfer, and the thermodynamic relationship between
the dihydropydines and their various reaction intermediates for
their mutual conversions, the following conclusions can be
made:
(1) The 45 dihydropyridine-type organic hydrides belong to
strong or middle-strong organic hydride donors. The hydride-
donating ability of them especially the one with strong electron-
donating groups at the pyridine ring is close to or even greater
than that of the well-known inorganic hydride donor, NaBH4.
It is evident that the 45 dihydropyridine-type organic hydrides
can construct a useful organic hydride donor library that the
hydride-donating abilities all are well-known. In the organic
hydrides library, 10H is the strongest hydride donor, but 16H
is the weakest hydride donor.
(2) Besides being used as good hydride source, the dihydro-
pyridine-type organic hydrides also can be used as good
hydrogen atom source. Since the hydrogen-donating abilities
of the dihydropyridine-type organic compounds all are much
greater than that of tocopherol (Vitamin E) (79.3 kcal mol-1),53
a well-known natural phenolic antioxidant, it is conceived that
the 45 dihydropyridine-type organic hydrides can also be used
as efficient antioxidants. According to the effect of the substit-
uents at the pyridine ring on the hydrogen-donating abilities,
the neutral pyridine-type radicals (X•) were suggested to be
electron-deficient radicals.
(3) One-electron-donating abilities of the dihydropyridine-
type organic hydrides (XH) are generally not strong, most are
smaller than that of ferrocene, which means that, when the
dihydropyridine-type organic hydrides are chosen as reducing
agents to reduce organic unsaturated compounds, the reductions
are generally initiated by charge transfer rather than by electron
transfer.
(9) The kinetics of hydride transfer from the dihydropyridine-
type organic hydrides is generally controlled by the thermody-
namic function entropy, but driven by the thermodynamic
function enthalpy.
(10) The idea of a thermodynamic characteristic graph (TCG)
of the dihydropyridine-type organic hydrides as an efficient
“Molecule ID Card” was introduced. The TCG not only can be
used to quantitatively diagnose and predict the characteristic
chemical properties of the dihydropyridines but also can be used
to quantitatively described the characteristic chemical properties
of the reaction intermediates of the dihydropyridines, which
means that the construction of TCG of compounds can create
a new access to quantitatively scale the chemical activities of
the reaction intermediates of organic compounds, such as radical,
radical cations, radical anions, carbocations, and carbanions.
It is evident that the determination of these hard-won and
fundamental thermodynamic data could not only supply a gap
of the thermodynamics of the dihydropyridine-type organic
hydrides as organic hydride source, but also would strongly
promote the application of the dihydropyridine-type organic
hydrides in the fields of organic syntheses chemistry, drug
chemistry, materials chemistry, hydrogen-energy source chem-
istry, and many others.
In addition, it is special to point out herein that the
significance of this work not only can guide experimental
chemists how to choose suitable hydride donor from the
dihydropyridine-type organic hydrides source as efficient organic
reductants but also even more importantly can provide theoreti-
cal chemists with a lot of useful thermodynamic experimental
data which is very required and indispensable to establish new
and reliable theoretical approaches to estimate the thermody-
namic potentials of new organic hydride source in solution.
Experimental Section
Materials. All reagents were of commercial quality from
freshly opened containers or were purified before use. Reagent-
grade acetonitrile was refluxed over KMnO4 and K2CO3 for
several hours and was doubly distilled over P2O5 under argon
(4) The radical cations of the dihydropyridine-type organic
compounds belong to strong proton donors (strong acids), and

2074 J. Phys. Chem. B, Vol. 114, No. 5, 2010
Zhu et al.
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before use. The commercial tetrabutylammonium hexafluoro-
phosphate (Bu4NPF6, Aldrich) was recrystallized from CH2Cl2
and was vacuum-dried at 383 K overnight before preparation
of supporting electrolyte solution. 9-Phenylxanthylium perclorate
(9-phenyl-Xn+ClO4-) and the 3-substitutent 1,4-dihydropy-
ridines XH were obtained according to literature methods10,39
1
and the final products were identified by H NMR and MS.
Measurment of Redox Potentials. The electrochemical
experiments were carried out by cyclic voltammetry (CV) and
osteryoung square wave voltammetry (OSWV) using a BAS-
100B electrochemical apparatus in deaerated acetonitrile under
argon atmosphere at 298 K as described previously.23 n-
Bu4NPF6 (0.1M) in acetonitrile was employed as the supporting
electrolyte. A standard three-electrode cell consists of a glassy
carbon disk as work electrode, a platinum wire as a counter
electrode, and 0.1 M AgNO3/Ag (in 0.1 M n-Bu4NPF6-
acetonitrile) as reference electrode. The ferrocenium/ferrocene
redox couple (Fc+/0) was taken as the internal standard. The
reproducibilities of the potentials were usually E5 mV for ionic
species and E10 mV for neutral species.
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Isothermal Titration Calorimetry (ITC). The titration
experiments were performed on a CSC4200 isothermal titration
calorimeter in acetonitrile at 298 K as described previously.14b
The performance of the calorimeter was checked by measuring
the standard heat of neutralization of an aqueous solution of
sodium hydroxide with a standard aqueous HCl solution. The
heat of reaction was determined following 10 automatic
injections from a 250 µL injection syringe containing a standard
solution into the reaction cell (1.30 mL) containing 1 mL other
concentrated reactant. Injection volume (10 µL) were delivered
0.5s time interval with 300-350s between every two injections.
The reaction heat was obtained by integration of each peak
except the first.71
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Kinetic Measurements. Kinetic measurements were carried
out in acetonitrile using a stopped-flow and UV/vis spectro-
photometer connected to a superthermostat circulating bath to
regulate the temperature of cell compartments. The oxidation
-
rate of XH by AcrH+ClO4 was measured at 25-45 °C by
-
monitoring the changes of absorption of AcrH+ClO4 at 415
nm under pseudo-first-order conditions (XH in over 20-fold
excess). The pseudo-first-order rate constants were then con-
verted to k2 by linear correlation of pseudo-first-order rate
constants against the concentrations of XH. The activation
parameters were derived from Arrhenius plots and from Eyring
plots.
Acknowledgment. Financial support from the Ministry of
Science and Technology of China (Grant No. 2004CB719905),
the National Natural Science Foundation of China (Grant Nos.
20921120403, 20832004, 20721062, and 20672060) and the 111
Project (B06005) is gratefully acknowledged.
Supporting Information Available: Detailed synthetic
routes and general preparation procedures of the 45 dihydro-
pyridines and the detailed 1H NMR data of some representative
dihydropyridines. This material is available free of charge via
the Internet at http://pubs.acs.org.
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JP911137P