Structural influences on the oxidation of a series of 2-benzothiazoline analogs

Article abstract of DOI:10.1016/j.molstruc.2011.12.001

We have examined the molecular and electronic structures of a number of benzothiazoline (Bt) and benzothiazole (oBt) analogs that possess phenyl and heterocycle substituents at the 2-position and discuss the ground-state factors that influence the relative rates at which these benzothiazolines are oxidized to benzothiazoles. Our studies indicate that the substituent at the 2-position in the benzothiazoline plays a fundamental role in governing the susceptibility of the species to oxidize. Our calculations for this series of compounds suggest that benzothiazolines that possess a heterocyclic R group oxidize faster than those with a phenyl group. The establishment of a favorable electrostatic interaction between the heteroatoms of the R and Bt/oBt fragments is a primary influence on this reaction while the establishment of π conjugation across the C_R-C_oBt bond is a minor effect.

Full text of DOI:10.1016/j.molstruc.2011.12.001

Journal of Molecular Structure 1011 (2012) 81–93
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Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Structural influences on the oxidation of a series of 2-benzothiazoline analogs
Matthew A. Lynn a, Lauren J. Carlson b, Hyeon Hwangbo b, Joseph M. Tanski c, Laurie A. Tyler b,
⇑
a Department of Science and Mathematics, National Technical Institute for the Deaf, Rochester Institute of Technology, Rochester, NY 14623, United States
b Department of Chemistry and Biochemistry, Union College, Schenectady, NY 12308, United States
c Department of Chemistry, Vassar College, Poughkeepsie, NY 12604, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 October 2011
Received in revised form 2 December 2011
Accepted 2 December 2011
Available online 17 December 2011
We have examined the molecular and electronic structures of a number of benzothiazoline (Bt) and ben-
zothiazole (oBt) analogs that possess phenyl and heterocycle substituents at the 2-position and discuss
the ground-state factors that influence the relative rates at which these benzothiazolines are oxidized
to benzothiazoles. Our studies indicate that the substituent at the 2-position in the benzothiazoline plays
a fundamental role in governing the susceptibility of the species to oxidize. Our calculations for this series
of compounds suggest that benzothiazolines that possess a heterocyclic R group oxidize faster than those
with a phenyl group. The establishment of a favorable electrostatic interaction between the heteroatoms
Keywords:
Benzothiazoline
Benzothiazole
Imine
of the R and Bt/oBt fragments is a primary influence on this reaction while the establishment of
p con-
jugation across the CRACoBt bond is a minor effect.
Ó 2011 Elsevier B.V. All rights reserved.
Oxidation
Density functional calculations
1. Introduction
In the last few years we and others have focused research ef-
forts on the synthesis, characterization, and study of heterocyclic
thiazoline-based molecules [1–3]. Unlike their oxygen-containing
counterparts, the oxazolines, thiazoline-based molecules have
been studied less and we are finding that they can exhibit unique
reactivity due to the sulfur atom. The thiazoline class of molecules
has proven useful in the preparation of a diverse range of organic
and inorganic systems. Indeed thiazolines can be used to prepare
a variety of organic functional groups including thiazoles, b-amino
thiols, aldehydes, and ketones to name a few [4,5]. Additionally,
numerous coordination complexes have been obtained by starting
with thiazoline-containing ligands. Some of these systems exhibit
unique reactivity as well as electrochemical and photophysical
properties and some have been employed as small molecule mim-
ics for metalloproteins and enzymes [6–8].
Scheme 1. Imine formation from a substituted 2-benzothiazoline molecule.
Scheme 2. Oxidation of a 2-benzothiazoline to a 2-benzothiazole.
It has been well documented in the field of inorganic chemistry
that the thiazoline group opens in the presence of base or metal ion
to form the corresponding imine (Scheme 1) [9,10]. As such, the cy-
clized thiazoline precursor gives this class of molecules an inherent
advantage as ligands, not only by providing N-, S-coordination
donors, but also inhibiting unwanted thiol oxidation.
A number of syntheses have been developed to obtain thiazoline-
based molecules [4,5] and 2-benzothiazoline (Bt) analogs can be
prepared by using a straightforward condensation reaction with
o-aminobenzenethiol (ABT) and an aldehyde group. Although liter-
ature reports indicate that this reaction proceeds unencumbered
[11,12], we experienced difficulties when carrying out reactions in
our lab. Parallel syntheses utilizing ABT with various heterocyclic-
substituted aldehydesresulted in theformation of both theexpected
2-thiazoline product as well as another product that we identified as
the oxidized, 2-benzothiazole (oBt) derivative (Scheme 2).
Several synthetic methods employing different oxidative tech-
niques have been reported for the conversion of a benzothiazoline
to a benzothiazole (MnO2 in benzene, BrCCl3/DBU) [13–15] and
⇑
Corresponding author. Tel.: +1 518 388 7123.
E-mail address: tylerl@union.edu (L.A. Tyler).
0022-2860/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2011.12.001

82
M.A. Lynn et al. / Journal of Molecular Structure 1011 (2012) 81–93
purchased from Aldrich Chemical Co. and used without further
purification. All solvents and chemicals were of reagent grade
and used without further purification.
2.2. Physical measurements
Infrared spectra were obtained with a Thermoelectron, Avatar
330 FT-IR spectrophotometer equipped with
reflectance insert, diamond window. 1H NMR spectra were re-
corded on Varian 200 MHz spectrometer or on Brüker
400 MHz spectrometer.
a Smart Orbit
a
a
2.3. Preparation of the benzothiazoline and benzothiazole analogs
Fig. 1. Abbreviations employed in this work (top) and representative examples of
benzothiazoline systems (bottom).
The new 2-benzothiazoline analogs, Ph(Bt), CF3Ph(Bt),
MeOPh(Bt) and Pyr(Bt), as well as those that were already known
were synthesized following a procedure similar to one that we
have previously published [3]. In each case 1 equiv of a substituted
aldehyde was dissolved in ꢀ20 mL of degassed ethanol (EtOH) to
which was then added 1 equiv of neat ABT under an N2 atmo-
sphere. The reaction was then refluxed for 2 h after which the sol-
vent was immediately removed in vacuo. The thiazoline product
precipitated from the solution as the volume was reduced in all
cases except Pyr(Bt). This reaction resulted in the formation of an
oil which could be solidified after trituration with diethyl ether
(Et2O). The solids were collected and dried under vacuum for
ꢀ12 h. Yields for the analogs ranged from 40% to 80%. In all cases
great care was taken to minimize exposure to oxygen.
The complete oxidation of the benzothiazolines to the corre-
sponding benzothiazoles was achieved by vigorously stirring a
solution of the analog dissolved in CHCl3 in an open flask for
ꢀ5 h at room temperature. The solvent was then removed via ro-
tary evaporation and the residue dried under high vacuum for
10 h. Yields of the benzothiazoles were quantitative.
some reports also indicate oxygen can be used [16,17] however lit-
tle mention of oxidation was noted in previous reports for the ben-
zothiazoline species under reaction conditions similar to ours.
Upon further investigation into the literature, we noted a curious
lack of spectroscopic data for some of the heterocycle-substituted
2-benzothiazoline (Bt) analogs. It also appeared that ligation reac-
tions with these analogs were problematic and many of the com-
plexes were incompletely characterized [11,18–20,12,21]. As
such, we were interested in acquiring the spectroscopic character-
ization for a set of substituted 2-benzothiazoline molecules useful
in inorganic synthesis as well as their oxidized derivatives, the
2-benzothiazoles (oBt), in order to provide a spectral comparison
[3]. The set included the pyridinyl- (Py-), thiophenyl- (Th-), and
furanyl- (Fu-) substituted heterocyclic 2-benzothiazolines and
2-benzothiazoles shown in Fig. 1 (bottom). The acronym for each
species was systematically assigned using an abbreviated form of
the starting aldehyde (R) followed by (Bt) or (oBt) to differentiate
between the thiazoline and the oxidized thiazole forms of the mol-
ecules respectively (see Fig. 1, top).
The spectroscopic data for the four new analogs and the oxi-
dized derivatives of each follows.
During the synthesis and characterization of this series of mol-
ecules, it became apparent that the substituent at the 2-position
plays a fundamental role in governing the susceptibility toward
oxidation of the 2-benzothiazolines. Therefore, as a follow up to
our initial work, we have undertaken additional studies aimed at
elucidating the structural and electronic factors responsible for
the observed reactivity differences within this series of 2-thiazo-
line molecules by analyzing the ground state energetics of the
set. This report, therefore, is directed toward defining the correla-
tion between the substituent at the 2-postion in the benzothiazo-
line analog and the molecule’s propensity to undergo oxidation to
the corresponding 2-thiazole. We have also expanded the set by
synthesizing four additional benzothiazoline analogs, shown in
Fig. 2, in order to afford a more comprehensive comparison.
2.4. Characterization of the analogs
2.4.1. Benzothiazoline derivatives
2.4.1.1. 2-Phenylbenzothiazoline (Ph(Bt)). White solid, mp 69–71 °C.
1H NMR (CDCl3, 200 MHz, 25 °C, d from TMS): 4.36 (s, 1H, NH), 6.38
(d, 1H), 6.72 (m, 2H), 6.99 (m, 2H), 7.34 (m, 3H), 7.55 (m, 2H). Se-
lected IR bands: (cmꢁ1) 3386 (m), 1579 (m), 1470 (s), 1260 (m),
743 (s), 695 (s).
2.4.1.2. 2-(p-Methoxyphenyl)benzothiazoline (MeOPh(Bt)). White so-
lid, mp 61–63 °C. 1H NMR (CDCl3, 400 MHz, 25 °C, d from TMS):
3.80 (s, 3H, CH3), 4.32 (s, 1H, NH), 6.38 (d, 1H), 6.65 (d, 1H), 6.77
(t, 1H), 6.92 (m, 3H), 7.06 (d, 1H), 7.50 (d, 2H). Selected IR bands:
(cmꢁ1) 1608 (m), 1578 (m), 1462 (m), 1247 (m), 1030 (m), 830
(m), 739(s).
2. Experimental
2.1. Materials
2.4.1.3. 2-(p-Trifluoromethylphenyl)benzothiazoline (CF3Ph (Bt)).
White solid, mp 106–108 °C. 1H NMR (CDCl3, 200 MHz, 25 °C, d
from TMS): 4.45 (s, 1H, NH), 6.42 (d, 1H), 6.77 (m, 2H), 7.03 (m,
2-Aminothiophenol, benzaldehyde, 4-methoxybenzaldehyde,
2-pyrrolecarboxaldehyde, and a,a,a-trifluoro-p-tolualdehyde were
Fig. 2. Phenyl-(Ph-), p-trifluoromethylphenyl-(CF3Ph-), p-methoxyphenyl (MeOPh-), and pyrrolyl-substituted (Pyr-) benzothiazoline analogs prepared as part of this study.

M.A. Lynn et al. / Journal of Molecular Structure 1011 (2012) 81–93
83
2H), 7.65 (d, 4H). Selected IR bands: (cmꢁ1) 1583 (m), 1475 (m),
1120 (m), 1106 (m), 1065 (s), 748 (s), 641 (s).
its ability to generate molecular structures that agreed well with
our experimentally obtained crystal structures of various benzo-
thiazoline and benzothiazole systems at reasonable computational
expense. All stationary points were identified as local minima
through the use of vibrational analysis.
2.4.1.4. 2-Pyrrolylbenzothiazoline (Pyr(Bt)). Brown oil. 1H NMR
(CDCl3, 400 MHz, 25 °C, d from TMS): 4.36 (s, 1H, NH), 6.17 (m,
1H), 6.24 (s, 1H), 6.50 (s, 1H), 6.64 (d, 2H), 6.81 (m, 2H), 6.98 (t,
1H), 7.08 (d, 1H), 8.74 (s, 1H). Selected IR bands: (cmꢁ1) 1567
(m), 1485 (m), 1438 (m), 1397 (m), 1102 (m), 1039 (m), 1018
3. Results and discussion
(m), 911 (m), 739(s). Selected IR bands: (cmꢁ1) 1580 (m,
1473(m), 975 (m), 743 (s).
tN@C),
3.1. Synthesis and spectral characterization
2.4.2. Benzothiazole derivatives
Oxidation of the 2-benzothiazoline group has been observed
since the 1930s when Lankelma and Sharnoff reported that benzo-
thiazolines react in the process of purification [27]. Likewise,
Yamamoto et al. have reported that 3-unsubstituted benzothiazo-
line derivatives are unstable in solution and also oxidize easily in
air [28]. In both of these examples the authors noted that the ben-
zothiazolines were oxidized to the corresponding benzothiazoles,
resulting in the formation of a C@N double bond within the ring
structure (Scheme 2). Although studies of N-alkylated benzothiaz-
olines have indicated that they are susceptible toward oxidation,
these compounds oxidize to generate products in which the five-
membered ring has opened [29]. In line with these former reports,
our own experience handling 2-benzothiazolines indicates that
they are prone to react in air and that some analogs are more sus-
ceptible toward oxidation than others. As such, the preparations
for the set of benzothiazoline molecules presented in this study
were carried out to carefully exclude oxygen to avoid contamina-
tion with the oxidized benzothiazole and afford clean spectro-
scopic characterization of each. The corresponding benzothiazole
analogs were isolated by vigorously stirring a chloroform solution
of the benzothiazoline in air, with complete oxidation occurring
after no more than 5 h. 1H NMR spectroscopy was used to monitor
the (Bt) ? (oBt) transformation as well as to confirm the purity of
each thiazoline and thiazole analog. Fig. 3 depicts the oxidation
reaction for MeOPh(Bt), monitored by 1H NMR spectroscopy
(CDCl3). The top spectrum of this figure shows clean MeOPh(Bt)
while the completely oxidized product, MeOPh(oBt), is evident in
the bottom spectrum.
2.4.2.1. 2-Phenylbenzothiazole (Ph(oBt)). Beige solid, mp 103 °C. 1H
NMR (CDCl3, 400 MHz, 25 °C, d from TMS): 7.42 (t, 1H), 7.53 (m,
3H), 7.93 (d, 1H), 8.13 (m, 3H). Selected IR bands: (cmꢁ1) 3386
(m), 1579 (m, tN@C), 1470 (s), 1260 (m), 743 (s), 695 (s).
2.4.2.2. 2-(p-Methoxyphenyl)benzothiazole (MeOPh(oBt)). White so-
lid, mp 121–123 °C. 1H NMR (CDCl3, 400 MHz, 25 °C, d from
TMS): 3.91 (s, 3H, CH3), 7.03 (d, 2H), 7.38 (t, 1H),7.49 (t, 1H),
7.90 (d, 1H), 8.06 (d, 3H). Selected IR bands: (cmꢁ1) 1604 (m,
tN@C),
1483 (m), 1309 (m), 1254 (s) 1171 (s), 1026 (m), 967 (s), 831 (s),
757 (s).
2.4.2.3. 2-(p-Trifluoromethylphenyl)benzothiazole (CF3Ph(oBt)). Yel-
low solid, mp 159–161 °C. 1H NMR (CDCl3, 400 MHz, 25 °C, d from
TMS): 7.46 (t, 1H), 7.56 (t, 1H), 7.78 (d, 2H), 7.96 (d, 1H), 8.13 (d,
1H), 8.23 (d, 2H). Selected IR bands: (cmꢁ1) 1585 (m,
tN@C), 1456
(m), 1433 (s) 1317 (m), 996 (m), 980 (s), 758 (s), 739 (s), 728 (s).
2.4.2.4. 2-Pyrrolylbenzothiazoline (Pyr(oBt). Beige solid, mp 100 °C,
decomp. 1H NMR (CDCl3, 400 MHz, 25 °C, d from TMS): 6.35 (m,
1H), 6.88 (s, 1H), 7.00 (s, 1H), 7.33 (t, 1H), 7.46 (t, 1H), 7.86 (d,
1H), 7.92 (d, 1H), 9.94 (s, 1H). Selected IR bands: (cmꢁ1) 3119
(w), 1570 (m, tN@C), 1486 (s), 1438 (s), 1397 (s), 1136 (m), 1040
(m), 912 (s), 740 (s).
2.5. X-ray data collection and structure solution and refinement
Single crystals suitable for X-ray analysis were obtained using
the following procedures: Diffusion of Et2O into separate chloro-
form solutions of Ph(Bt) and Py(Bt) resulted in the formation of yel-
low and colorless plates of each analog respectively within 24 h.
Slow evaporation of separate solutions of Py(oBt) and Ph(oBt) re-
sulted in the formation of colorless blocks of each species. X-ray
diffraction data were collected on a Bruker APEX 2 CCD platform
Several pieces of spectroscopic information can be used to
determine the degree to which the oxidation reaction has occurred.
First, there are two distinct resonances present in the 1H NMR
spectrum of MeOPh(Bt) that can be used to identify the benzo-
thiazoline group. One resonance, located between ꢀ4.4 and
5.1 ppm, is assigned to the benzothiazoline NAH as confirmed by
D2O exchange. The other resonance, attributed to the thiazoline
CAH proton, appears as a singlet between 6.3 and 6.7 ppm. The
NAH peak can be broad which makes the thiazoline CAH reso-
nance a better indicator for the presence of this species and a good
gauge to determine the extent of oxidation. Additionally, 1H NMR
spectra show that as the benzothiazolines oxidize there is a con-
comitant downfield shift in the aromatic resonances, most likely
due to the extended conjugation between the two ring systems
upon oxidation. The second method includes analysis of the IR
spectra for the (Bt) and (oBt) analogs which reveals only slight dif-
ferences between the two forms, including the appearance of a
medium intensity band ꢀ1600 cmꢁ1 that can be assigned to the
diffractometer (MoKa (k = 0.71073 Å)) equipped with an Oxford li-
quid nitrogen cryostream. Crystals were mounted in a nylon loop
with Paratone-N cryoprotectant oil. The structures were solved
using direct methods and standard difference map techniques,
and were refined by full-matrix least-squares procedures on F2
with SHELXTL (Version 6.14) [22]. All non-hydrogen atoms were
refined anisotropically. Hydrogen atoms on carbon were included
in calculated positions and were refined using a riding model. Crys-
tal data and refinement details are presented in Table 1 for all spe-
cies while selected bond distances and angles are listed in Table 2
and Table 3 respectively.
thiazole tC@N
.
2.6. Computational details
Although the benzothiazoline NAH bond clearly plays a role in
the oxidation process, we have found that the propensity of a benzo-
thiazoline to undergo oxidation to form the corresponding
benzothiazole is also directly dependent on the molecular structure
of the ring system bound to the 2-position. The relative rates of
reactions occur in the following order for the set of seven analogs
we have studied: Fu(Bt) ꢀ Pyr(Bt) > Thio(Bt) > Ph(Bt) > CF3Ph(Bt) >
MeOPh(Bt) > Py(Bt), from fastest to slowest. In order to obtain this
All calculations were performed using the Intel Macintosh ver-
sion of Gaussian 03, Revision E.01 [23]. The gas-phase equilibrium
geometries of the benzothiazolines and benzothiazoles were opti-
mized by the hybrid density functional B3LYP method [24–26]. The
6-31G(d) basis set was used as supplied with the software. This
combination of functional and basis set was chosen because of

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M.A. Lynn et al. / Journal of Molecular Structure 1011 (2012) 81–93
Table 1
Summary of crystal data and intensity collection and structure refinement parameters for thiazoline and thiazole analogs.
Ph(Bt)
13H11NS
Py(Bt)
Ph(oBt)
Py(oBt)
Empirical formula
Molecular Weight
Crystal color, habit
Crystal size (mm)
Temperature (K)
Crystal System
C
C12H10N2S
214.28
C13H9NS
211.27
C12H8N2S
212.26
213.29
Yellow, plate
0.33 ꢂ 0.14 ꢂ 0.04
125(2)
Triclinic
P-1
Colorless, plate
0.15 ꢂ 0.05 ꢂ 0.01
125(2)
Orthorhombic
P2(1)2(1)2(1)
Colorless, block
0.27 ꢂ 0.10 ꢂ 0.08
125(2)
Orthorhombic
Pna2(1)
Colorless, block
0.23 ꢂ 0.13 ꢂ 0.13
125(2)
Orthorhombic
Pca2(1)
Space group
Unit cell dimensions
a (Å)
b (Å)
c (Å)
8.4439(1)
11.1521(2)
11.3664(2)
89.661(2)
88.568(2)
87.174(2)
1068.7(3), 4
1.326
6.1793(6)
8.6385(9)
19.256(2)
90
90
90
1027.90(2), 4
1.385
0.278
16.1330(1)
11.0617(9)
5.7804(5)
90
90
90
1031.56(2), 4
1.360
0.274
13.7445(6)
13.0249(6)
11.0599(5)
90
90
90
1979.95(2), 8
1.424
0.289
a
(°)
b (°)
c
(°)
V (Å3), Z
Dcalc (mg mꢁ3
)
Absorption coeff. (
l
, mmꢁ1
)
0.265
U
Range collected (°)
1.79–28.33
98.7
2.12–24.72
100
2.23–24.75
99.9
1.56–29.13
100
Completeness to
U max (%)
Reflns collected/unique (R(int))
Data/restraints/parameters
R1, wR2 (I > 2rI)
13829/5261 (0.0315)
5261/2/277
0.0602, 0.1599
0.0807, 0.1750
1.074
10361/1761 (0.1008)
1761/1/139
0.0415, 0.0634
0.0721, 0.0727
1.050
9840/1756 (0.0651)
1756/443/273
0.0299, 0.0593
0.0345, 0.0606
1.173
26392/5320 (0.0323)
5320/1/272
0.0536, 0.1399
0.0581, 0.1443
1.055
R1, wR2 (all data)
Goodness of fit on F2
Largest diff peak/hole (e/Å3)
Absolute structure parameter
1.041, ꢁ0.434
0.220, ꢁ0.228
0.091, ꢁ0.116
2.606, ꢁ0.498
0.51(1)
ꢁ0.11(9)
0.00(9)
Table 2
Table 3
Selected bond distances (Å) for thiazoline and thiazole analogs determined by X-ray
crystallography.
Selected bond angles (°) for thiazoline and thiazole analogs determined by X-ray
crystallography.
Ph(Bt)
Ph(Bt)
S(1)AC(11)
S(1)AC(18)
C(11)AN(1)
N(1)AC(113)
N(1)AH(1)
S(2)AC(21)
S(2)AC(28)
C(21)AN(2)
N(2)AC(213)
N(2)AH(2)
1.852(3)
1.760(3)
1.451(3)
1.387(3)
0.878(2)
1.847(3)
1.767(3)
1.456(3)
1.384(3)
0.874(2)
C(11)AC(12)
C(11)AH(11A)
C(12)AC(17)
C(12)AC(13)
C(18)AC(113)
C(21)AC(22)
C(21)AH(21A)
C(22)AC(27)
C(22)AC(23)
C(28)AC(213)
1.513(3)
1.0000
C(18)AS(11)AC(11)
C(11)AN(1)AC(113)
C(17)AC(12)AC(11)
C(11)AN(1)AH(1)
C(28)AS(21)AC(21)
C(21)AN(2)AC(213)
C(27)AC(22)AC(21)
C(21)AN(2)AH(2)
91.46(1)
114.8(2)
121.9(2)
118.2(2)
91.10(1)
114.4(2)
122.6(2)
122.2(2)
N(1)AC(11)AC(12)
N(1)AC(11)AS(1)
C(13)AC(12)AC(17)
N(2)AC(21)AC(22)
N(2)AC(21)AS(2)
C(23)AC(22)AC(27)
115.8(2)
103.27(2)
118.9(2)
115.5(2)
103.49(2)
119.0(2)
1.399(3)
1.393(4)
1.398(3)
1.524(3)
1.0000
1.391(3)
1.392(4)
1.405(3)
Py(Bt)
C(8)ASAC(1)
C(1)AN(1)AC(13)
C(7)AC(2)AC(1)
C(1)AN(1)AH(1)
89.98(1)
111.1(2)
123.4(3)
111.8(2)
N(1)AC(1)AC(2)
N(1)AC(1)AS
N(2)AC(2)AC(7)
115.3(3)
103.78(2)
122.8(3)
Py(Bt)
SAC(1)
SAC(8)
C(1)AN(1)
N(1)AC(13)
N(1)AH(1)
1.776(3)
1.841(3)
1.464(4)
1.401(4)
0.897(2)
C(1)AC(2)
C(1)AH(1B)
C(2)AC(7)
N(2)AC(2)
C(8)AC(13)
1.501(4)
1.0000
1.383(4)
1.349(3)
1.393(4)
Ph(oBt)
C(8)ASAC(1)
C(1)ANAC(13)
C(7)AC(2)AC(1)
88.5(2)
110.3(4)
119.8(5)
NAC(1)AC(2)
NAC(1)AS
C(3)AC(2)AC(7)
122.7(4)
116.0(3)
120.4(5)
Ph(oBt)
SAC(1)
SAC(8)
C(1)AN
NAC(13)
1.749(4)
1.718(4)
1.297(5)
1.390(5)
C(1)AC(2)
C(2)AC(7)
C(2)AC(3)
C(8)AC(13)
1.496(6)
1.378(6)
1.371(6)
1.389(5)
Py(oBt)
C(18)AS(11)AC(11)
C(11)AN(11)AC(113)
C(7)AC(2)AC(1)
C(28)AS(21)AC(21)
C(21)AN(21)AC(213)
C(27)AC(22)AC(21)
88.77(2)
109.1(3)
121.4(3)
88.61(1)
110.0(2)
121.2(2)
N(11)AC(11)AC(12)
N(11)AC(11)AS(11)
N(12)AC(12)AC(17)
N(21)AC(21)AC(22)
N(21)AC(21)AS(21)
N(22)AC(22)AC(27)
123.1(3)
117.2(3)
123.9(3)
123.0(2)
116.5(2)
123.0(3)
Py(oBt)
S(11)AC(11)
S(11)AC(18)
C(11)AN(11)
N(11)AC(113)
S(21)AC(21)
S(21)AC(28)
C(21)AN(21)
N(21)AC(213)
1.747(3)
1.750(3)
1.300(4)
1.392(4)
1.751(3)
1.742(3)
1.305(3)
1.389(3)
C(11)AC(12)
C(12)AC(17)
C(12)AN(12)
C(18)AC(113)
C(21)AC(22)
C(22)AC(27)
C(22)AN(22)
C(28)AC(213)
1.474(4)
1.406(5)
1.341(5)
1.403(5)
1.470(4)
1.388(4)
1.344(4)
1.405(4)
tronic factors responsible for the observed reactivity differences
within this series of molecules.
3.2. Crystallographic structures of compounds
In order to provide a structural comparison between the
thiazoline and thiazole forms of a molecule as well determine
any structural differences that may be present between the differ-
ent (Bt) and (oBt) moieties, X-ray crystallographic studies were
carried out on Ph(Bt), Py(Bt), Ph(oBt) and Py(oBt). Although the
syntheses for Py(Bt) and Py(oBt) have been reported previously
[3], we report the structures here for the first time. For clarity
ranking, studies using 1H NMR spectroscopy were performed that
followed the conversion of the benzothiazoline to thiazole over
time.
In the following discussions, X-ray crystallographic analyses
and detailed computational studies of the (Bt) and (oBt) analogs
are presented to elucidate the structural and ground-state elec-

M.A. Lynn et al. / Journal of Molecular Structure 1011 (2012) 81–93
85
Fig. 3. Conversion of MeOPh(Bt) (top spectrum) to MeOPh(oBt) (bottom spectrum) over time followed by 1H NMR spectroscopy (CDCl3).
and ease of comparison, the numbering scheme between the four
structures has been conserved.
structure of Py(Bt) is shown in Fig. 5; this compound crystallizes
as a racemic twin. While bond lengths for both sets of molecules
are listed in Table 2, for discussion purposes the averages are used.
Comparison of the X-ray crystallographic data for Ph(Bt) and
Py(Bt) reveals that the two structures are similar. The difference
ꢀ0.01 Å between the C(1)AC(2) bond lengths suggests that the
bond order between these two atoms that join the thiazoline
portion of the molecule and the substituent derived from the start-
ing aldehyde is nearly equivalent between the two species. A
3.2.1. Structures of Ph(Bt) and Py(Bt)
The X-ray analysis of Ph(Bt) revealed two independent mole-
cules that in the asymmetric unit (Fig. 4). The highest difference
peak of 1.041 e/Å3 is found next to sulfur, the heavy atom in the
structure. The bond lengths between the two molecules are simi-
lar, with differences less than 0.01 Å for analogous distances. The
Fig. 4. Thermal ellipsoid plot (30% probability level) of Ph(Bt) showing the numbering scheme. Two independent molecules are in the unit cell.

86
M.A. Lynn et al. / Journal of Molecular Structure 1011 (2012) 81–93
Fig. 5. Thermal ellipsoid plot (30% probability level) of Py(Bt) showing the
numbering scheme.
comparable difference is noted in the C(1)AN(1) bond lengths
within the thiazoline ring structure which measure 1.454(3) and
1.464(4) for Ph(Bt) and Py(Bt) respectively. There are however
two main differences between these thiazoline analogs. The first
in the C(1)AS bond lengths which measure 1.850(3) Å in Ph(Bt)
and 1.776(3) Å in Py(Bt), a difference of ꢀ0.07 Å. The other differ-
ence between the two structures is that Py(Bt) exhibits a one
dimensional hydrogen-bonding chain between the NAH in the
thiazoline portion of the molecule with the pyridine nitrogen of a
neighboring molecule. The N1ꢃ ꢃ ꢃN2i distance is 3.119(3) Å (sym-
metry codes: (i) x + 1/2, ꢁy1/2, ꢁz + 1). A structure showing this
interaction is available in the Supplementary material. Ph(Bt) does
not contain a heterocyclic substituent that can participate in H-
bonding and no intermolecular hydrogen-bonding interaction oc-
curs between the thiazoline nitrogen and thiazoline hydrogen of
separate molecules.
Fig. 7. Thermal ellipsoid plot (30% probability level) of both Py(oBt) molecules that
cocrystallize within asymmetric unit. The numbering scheme is shown.
with similar lengths measured for Ph(oBt) and Py(oBt) (1.496(3)
and 1.472(4) Å respectively). This change, however, is smaller than
that for the C(1)AN(1) bond length upon oxidation. A difference of
ꢀ0.023 Å is noted for Ph(Bt) ? Ph(oBt) while the analogous differ-
ence for the pyridine analog was found to be ꢀ0.029 Å. Similarly,
we observe that the C(1)AS bond lengths, which differed by
ꢀ0.07 Å between the Ph(Bt) and Py(Bt) analogs, become identical
upon oxidation: 1.749(4) Å for Ph(oBt) and 1.749(3) Å for Py(oBt).
3.3. Computational analysis
3.2.2. Structures of Ph(oBt) and Py(oBt)
3.3.1. Computational details of 2-benzothiazoline systems
The structure of Ph(oBt) is shown in Fig. 6. The planar structure
exhibits a twofold whole-molecule disorder that refined to 60/40
occupancy. A figure depicting this disorder is available in the Sup-
plementary material. The disorder was refined with the help of
similarity restraints on displacement parameters and rigid bond
restraints on 1–2 and 1–3 distances and displacement parameters
for all carbon atoms. The structure of Py(oBt) is shown in Fig. 7.
Like Ph(Bt), Py(oBt) also crystallizes as two independent molecules
in the asymmetric unit. The highest difference peak of 2.606 e/Å3 is
found next to the sulfur, the heavy atom in the structure. For both
Ph(oBt) and Py(oBt), average bond lengths and angles will be used
for the discussion while separate values are listed in Tables 2 and 3.
As expected, the C(1)AN(1) bond distances in both species de-
crease upon oxidation. These bond lengths for the two molecules
An examination of the effect that a particular R group has on the
oxidation of the various benzothiazoline systems prepared here
first requires an understanding of the molecular structures of these
compounds. Density functional theory, as implemented in the
Gaussian 03 software package, was therefore employed to deter-
mine the optimized geometry of each R(Bt) molecule in the ground
state. A ball-and-stick depiction of Ph(Bt), the structure for which
is representative of most of the other R(Bt) systems, is shown at
the top of Fig. 8. A number of atoms in this figure are labeled with
subscripts that reference the portion of the molecule where they
are located (e.g., NBt, the nitrogen atom in the benzothiazoline frag-
ment; CoBt, the carbon atom at the 2 position of the benzothiazole).
Various optimized bond lengths, angles, and dihedral angles for
these systems are provided in Table 4.
are nearly identical (
D
ꢀ 0.006 Å) and measure 1.297(3) and
Comparison of the computationally optimized values in Table 4
with the crystallographically determined parameters in Tables 2
and 3 shows that the various optimized bond lengths and angles
in the optimized structures compare well with the same parameters
determined from the crystal structures. The CAC bond that bridges
the Bt and R groups similarly falls within a narrow range of 1.483–
1.511 Å. Furthermore, across the range of compounds, the
HACBtACR angle of approximately 109° is what would be expected
for the tetrahedral carbon atom of the Bt unit (CBt). The values in
parentheses in Table 4 show that the various optimized bond
lengths and angles in the optimized structures compare well with
the same parameters determined from the crystal structures.
Presented in Table 5 are the charges calculated for various
atoms of the Bt unit and for the R group as a whole. It can be seen
that these values vary little among this series of compounds and
show no apparent trend from Py(Bt), which is oxidized the slowest,
to Fu(Bt) and Pyr(Bt), which react the fastest. As was the case for
the optimized bond lengths, angles, and dihedral angles presented
in Table 4, the charges on the various atoms lie within narrow
ranges and do not increase or decrease in a manner that correlates
with the observed relative rates of reaction. In fact, the total charge
1.303(3) Å for Ph(oBt) and Py(oBt) respectively. This structural
change reflects a shortening of the C(1)AN(1) distances in going
from (Bt) ? (oBt) in both species by ꢀ0.16 Å upon oxidation and
represents the conversion of a CAN single bond into a C@N double
bond. The C(1)AC(2) bond distance also decreases upon oxidation
Fig. 6. Thermal ellipsoid plot (30% probability level) of Ph(oBt) showing the
numbering scheme.

M.A. Lynn et al. / Journal of Molecular Structure 1011 (2012) 81–93
87
Fig. 8. DFT-optimized structures for Ph(Bt) and Ph(oBt) with atom-labeling scheme used herein.
Table 4
Structural parameters for the DFT-optimized ground-state structures of R(Bt). A positive dihedral angle indicates that the fourth atom (E) is rotated toward NBt while a negative
angle means that it is rotated toward SBt
.
BtACBtACRAE0R dihedral angle (°)
ꢁ15.3 (E = CPh
97.5 (E = NPy
ꢁ17.8 (E = CCF3Ph
ꢁ17.9 (E = CTh
ꢁ13.6 (E = CMeOPh
ꢁ28.0 (E = OFu
ꢁ11.9 (E = CPyr
R
S
BtACBt (Å)
N
BtACBt (Å)
C
BtACR (Å)
HBtACBtACR angle (°)
H
Ph
Py
CF3Ph
Th
MeOPh
Fu
1.874
1.861
1.873
1.880
1.877
1.884
1.886
1.464
1.463
1.463
1.464
1.465
1.462
1.471
1.510
1.536
1.511
1.491
1.506
1.486
1.483
109.1
108.2
109.1
108.2
109.1
108.9
108.9
)
)
)
)
)
)
)
Pyr
of the R fragment decreases from R = Ph to R = Th and then in-
creases from R = Th to R = Pyr such that the total charge on the
phenyl portion of Ph(Bt) (0.111) is similar to that for the pyrrolyl
fragment of Pyr(Bt) (0.134). What does seem important, however,
is the nature of the charge (either positive or negative) on several
individual atoms in the Bt fragment. Our calculations determine
that there is a positive charge in the range of +0.132 to +0.162 on
SBt and a negative charge of ꢁ0.621 to ꢁ0.653 on NBt. As will be
discussed shortly, this separation of charges within the Bt fragment
itself plays an important role in the propensity of the R(Bt) systems
to oxidize.
Table 5
Atomic charges for SBt, NBt, and CBt atoms in R(Bt) as well as the H atoms bound to the
C and N atoms of the Bt fragment. Also shown is the total sum of atomic charges for
each R group.
R
SBt
NBt
CBt
HCBt
HNBt
R
Ph
Py
CF3Ph
Th
MeOPh
Fu
+0.153
+0.132
+0.161
+0.162
+0.148
+0.159
+0.141
ꢁ0.643
ꢁ0.621
ꢁ0.645
ꢁ0.646
ꢁ0.642
ꢁ0.646
ꢁ0.653
ꢁ0.204
ꢁ0.225
ꢁ0.205
ꢁ0.177
ꢁ0.205
ꢁ0.212
ꢁ0.217
+0.166
+0.197
+0.170
+0.176
+0.170
+0.182
+0.175
+0.319
+0.342
+0.321
+0.324
+0.321
+0.322
+0.321
+0.111
+0.079
+0.088
+0.055
+0.088
+0.090
+0.134
Pyr
The one R(Bt) system for which Gaussian locates a ground-state
structure that is different than the others is Py(Bt). Ball-and-stick
representations of two perspectives of this molecule are shown
in Fig. 9. Comparing this structure with that for Ph(Bt) (Fig. 8),
the phenyl and pyridinyl rings are computed to be in orientations
that are perpendicular to each other relative to the benzothiazo-
line fragments in the two molecules. The HBtACBtACPyANPy dihe-
dral angle between the Py and Bt portions of the molecule is
97.5°, considerably different than the approximately 15° calcu-
lated for the analogous angle in other R(Bt) systems. This differ-
ently configured lowest energy structure for Py(Bt) is found
because of an electrostatic attraction between the positive charge
(+0.342) on the H atom bound to NBt and the negative charge
(ꢁ0.489) and available lone pair of electrons on NPy. Similar com-
putational [30,31] and experimental [32] findings have been made
for substituted thiazolines and related systems with recent work
[33] focusing on the effect of solvation on such compounds. This
interaction provides for a slightly more stable molecular structure
than if the Py ring were oriented similar to the R groups in other
R(Bt) systems. It is also possible to locate a structure for Py(Bt) like
those for the other R(Bt) systems in which the plane of the Py

88
M.A. Lynn et al. / Journal of Molecular Structure 1011 (2012) 81–93
fragment is approximately perpendicular to that of the Bt portion
of the molecule, but this structure is 1.31 kcal/mol less stable than
the one shown in Fig. 9.
3.3.2. Computational details of 2-benzothiazole systems and
implications for oxidation
Upon oxidation, several important structural changes occur as
If there is indeed such a long-range interaction between the
lone pair of electrons on NPy and HBt such that the lowest energy
molecular structure for Py(Bt) is not like that shown in Fig. 8 for
the phenyl-substituted benzothiazoline, it must be explained why
similar structures are not found for the two other molecules that
R(Bt) becomes R(oBt). CBt and NBt gain p orbitals that can interact
p
with the
all of the R groups being considered here possess their own
tems, each of the R(oBt) systems can have a conjugated system
p
system of the rest of the Bt fragment. Further, because
p
sys-
p
that extends across the entire molecule when the R and oBt frag-
ments are coplanar. Geometry optimizations of the various
R(oBt) systems do indicate that the lowest energy structure for
each molecule is indeed planar in agreement with the crystal struc-
tures (Figs. 6 and 7). A representative computed structure, that for
(Ph(oBt)), is displayed at the bottom of Fig. 8.
One important aspect to understanding the structures of the
R(oBt) systems is that some of them have a non-symmetric, het-
eroatom-containing R group. For R = Fu, Th, Py, and Pyr, the pres-
ence of the O, S, or N atom in the ring means that two different
conformers can be generated depending on whether the hetero-
atom is located syn to NoBt or to SoBt. The differences in total energy
between the two conformations for each of these molecules are:
1.46 kcal/mol (Th(oBt)), 2.16 kcal/mol (Fu(oBt)), 3.46 kcal/mol
(Pyr(oBt)), and 6.72 kcal/mol (Py(oBt)). The orientation with the
lower energy for Py(oBt) has the Npy atom syn to SoBt in agreement
with this compound’s crystal structure (Fig. 7). Similarly, our calcu-
lations find that the lower energy planar structure for Fu(oBt) has
possess an R group having a heteroatom with an available
r-type
lone pair of electrons, namely Fu(Bt) and Th(Bt). A structure for
Fu(Bt) that is oriented like that shown in Fig. 9 can indeed be lo-
cated, but the total energy of the structure is 0.46 kcal/mol less
stable than the structure analogous to that shown in Fig. 9 even
though the charge on the O atom is similar (ꢁ0.44) to that found
for NPy. The OFuAHBt distance in this furanyl system is 2.675 Å,
which is 0.475 Å longer than the NPyAHBt distance in Py(Bt). This
difference between these two molecules is a result of two factors.
First, the electron pair on the more electronegative O atom of Fu
is less available than is the lone pair on the less electronegative
NPy. Second, the oxygen atom of the five-membered furanyl ring
is farther away from the NBt H atom than is the nitrogen atom
of the six-membered pyridinyl ring. As for Th(Bt), the charge cal-
culated for STh is +0.28, so a long-range electrostatic attraction be-
tween it and the positively charged H atom bound to NBt does not
occur.
Fig. 9. Two perspectives of the DFT-optimized structure of Py(Bt).

M.A. Lynn et al. / Journal of Molecular Structure 1011 (2012) 81–93
89
Table 7
the OFu atom syn to SoBt. As for Th(oBt) and Pyr(oBt), the lower en-
ergy structures have the S and NAH units, respectively, syn to NoBt
Calculated NLMO bond orders for the CRACoBt bonds in the various R(oBt) systems. An
.
asterisk (⁄) indicates the more stable conformation of R(oBt).
Although this point will be discussed further shortly, it is impor-
tant to recognize that for the lower energy R(oBt) conformation,
each of these R group heteroatoms (or NAH unit in the case of
the pyrrole analog) is located syn to the Bt heteroatom that has a
charge of the opposite sign. This finding is presented graphically
in electrostatic potential (ESP) plots for the R(oBt) systems. In each
of these depictions, the location of the most negative ESP values (as
indicated by the strongest red shading) is NoBt. Of particular note
are those systems (R = Py and Fu) that have an electronegative N
or O atom with red ESP shading located anti to NoBt and the pyrr-
olyl-substituted system that has a deep blue ESP shading on the
electropositive H atom of the NPyrAH moiety syn to NoBt. These
plots can be found in the Supplementary material. Similar results
have been reported for pyrrolyl- and other N-based heterocylic
systems, including peptides, in which electrostatic interactions
R
Conformation
Not applicable
CRACoBt NLMO bond order
Ph
1.0554
1.0413
1.0378
1.0501
1.0693
1.0639
1.0609
1.0690
1.0707
1.0896
1.0887
Py⁄
N
N
pyASoBt syn
pyANoBt syn
Py
CF3Ph
Th⁄
Th
Not applicable
S
S
ThANoBt syn
ThASoBt syn
MeOPh
Not applicable
Fu⁄
O
O
FuASoBt syn
FuANoBt syn
Fu
Pyr⁄
Pyr
NAHPyrANoBt syn
NAHPyrASoBt syn
(i.e., R = Fu, Pyr, and Th) are found to have the shortest optimized
CRACoBt bond lengths if by only several hundredths of an
Ångstrom.
(including H-bonding) are possible between adjacent p-conjugated
rings and other functional groups [34–37]. Such arguments have
also been recently employed to explain structural preferences of
substituted pyrans [38] and carbohydrates. [39,40] In the lower en-
ergy conformation of Th(oBt), STh has a charge of +0.31 and is lo-
cated syn to NoBt, which has a charge of ꢁ0.52. As for Fu(oBt),
the lower energy structure has OFu with a charge of ꢁ0.44 syn to
Another way to probe the relative strengths of the CRACoBt
p
bond is through an examination of calculated bond orders. Gauss-
ian provides such information through the Natural Localized
Molecular Orbital (NLMO) analysis [41]. The calculated NLMO
bond orders for the CRACoBt bonds in each of the R(oBt) systems
are provided in Table 7 and the NLMO bond orders are shown in
Fig. 10 for all of the bonds in Ph(oBt). As can be seen from
Table 7, the calculated NLMO bond orders for these systems show
an approximate trend of higher bond order for the products of the
faster oxidation reactions and yet these values only span a narrow
range from 1.04 to 1.09. Perhaps more importantly, these values
suggest that the CRACoBt bonds for all of these systems are barely
stronger than a single bond. Examination of all of the NLMO bond
orders provided in Fig. 10 shows that these values are probably an
underestimation of the actual bond orders, given that the calcu-
lated values for all of the CAH bonds are approximately 0.74 for
bonds that would ordinarily be considered to be single bonds with
bond orders of 1.00. Yet compared to the bond orders for the other
carbon–carbon bonds of Ph(oBt), which range from 1.20 to 1.75,
the bond between CPh and CoBt is the weakest carbon–carbon bond
in the molecule. In line with the observation from Table 6 that the
slightly shorter CRACoBt bond lengths belong to the systems that
oxidize faster, the calculated NLMO bond orders are slightly higher
for the same compounds. Furthermore, the CRACoBt bond order for
different conformations of each of the four systems that can give
rise to two different conformers are nearly identical, regardless
of the way in which the R group rotates. In three cases (R = Py,
Th, Pyr), the bond order is higher for the more stable conformation
while it is lower for the fourth (R = Fu).
SoBt, which has a charge of +0.23. Computationally, Remko and
coworkers made a similar finding in their examination of a
2-substituted thiazoline and related species [30].
Various optimized structural parameters for all of the R(oBt)
systems are provided in Table 6. The bond lengths determined
from the crystal structures (shown in parentheses in Table 6) com-
pare well with those from the Gaussian-optimized structures. For
those systems for which two conformations are possible, the com-
puted bond lengths are shown for the more stable structure. Exam-
ining the calculated changes in bond lengths upon oxidation (also
shown in Table 6) shows that all of the bonds to the CBt/oBt atom
become shorter upon oxidation. The largest change occurs for the
NAC bond as it shortens approximately 0.16 Å as both the NBt
and CBt atoms lose a bond to a H atom and gain a p-bonding inter-
action to each other. The SAC bond shortens by ca. 0.09 Å such that
this bond has a similar length (ꢀ1.79 Å) across the series of com-
pounds, as discussed previously for the crystal structures. The
CRACBt/oBt bond, which bridges the two ring sections of the mole-
cule, shortens by an average of 0.05 Å, exhibits a rather small
change despite the change in geometry of the CBt/oBt atom upon
oxidation and the resulting system-wide
p conjugation that can
be established. Furthermore, the range of CRACoBt bond lengths cal-
culated is quite narrow with a spread of only 0.030 Å separating
the longest from the shortest while the actual optimized bond
length of ca. 1.46 Å is longer than what might be expected (ca.
1.39 Å) for a bond connecting two C atoms that are both trigonal
A molecular orbital (MO) examination of the p-type orbitals in
Ph(oBt) explains our observation that the carbon–carbon bond that
bridges the R and oBt units is relatively weak. Shown in Fig. 11 is
an MO diagram for Ph(oBt) in which only the occupied orbitals of
planar. This observation suggests that the CRACoBt
p bond is weak-
er than would be expected for a conjugated bond. Of particular
p
p
symmetry are depicted. Not shown in this figure are the molec-
note is the observation that the compounds that oxidize the fastest
ular orbitals of symmetry, which are interspersed with those
r
Table 6
Structural parameters for the most stable Gaussian-optimized ground-state conformations of R(oBt). Values in parentheses indicate the bond length from the crystal structures
obtained as part of this study and are provided for comparison to the computed values.
R
SoBtACoBt (Å)
N
oBtACoBt (Å)
C
oBtACR (Å)
Calculated change in bond length upon oxidation
oBtACoBtASBtACoBt (Å) oBtACoBtANBtACoBt (Å)
S
N
CoBtACRACBtACR (Å)
Ph
Py
CF3Ph
Th
MeOPh
Fu
1.792 (1.749)
1.778 (1.749)
1.789
1.790
1.794
1.299 (1.297)
1.299 (1.303)
1.299
1.300
1.299
1.469 (1.496)
1.469 (1.472)
1.470
1.446
1.465
ꢁ0.082
ꢁ0.083
ꢁ0.084
ꢁ0.090
ꢁ0.083
ꢁ0.099
ꢁ0.103
ꢁ0.165
ꢁ0.164
ꢁ0.164
ꢁ0.164
ꢁ0.166
ꢁ0.161
ꢁ0.166
ꢁ0.041
ꢁ0.067
ꢁ0.041
ꢁ0.045
ꢁ0.042
ꢁ0.044
ꢁ0.043
1.785
1.783
1.301
1.305
1.442
1.440
Pyr

90
M.A. Lynn et al. / Journal of Molecular Structure 1011 (2012) 81–93
Fig. 10. Calculated NLMO bond orders for all bonds in Ph(oBt).
shown in the diagram. Paired arrows in a given molecular orbital
represent the highest occupied orbital for the molecule and mole-
and 1.06, respectively. Therefore, for the R(oBt) systems, occupa-
tion of orbital 8a00 with its p⁄ character across the bridging carbon
atoms significantly reduces the CRACoBt bonding character as com-
pared to a molecule for which this molecular orbital is not
occupied.
cule fragments; there are no occupied
higher in energy than the highest occupied
the left side of the diagram are the three occupied
r
-type orbitals that are
-type orbitals. On
-type orbitals
p
p
for the phenyl group shown here as derived from benzene: the
completely bonding a2u orbital is below the partially bonding eg
degenerate pair. Although these group theoretical labels are only
truly correct for a benzene molecule having D6h symmetry, they
shall be used here to differentiate them from the other fragment
and molecular orbitals shown in the figure. As for the oBt unit on
the right, there are five fragment orbitals that are electronically
To summarize, there seem to be two electronic factors, one ma-
jor and one minor, that contribute to the relative rates of oxidation
that are observed experimentally: an electrostatic attraction be-
tween heteroatoms in the R and Bt/oBt fragments and some minor
influence from the establishment of system-wide
p conjugation
upon oxidation. With the exception of the pyridinyl-substituted
system, the compounds that have heterocyclic R groups oxidize
faster than those that possess substituted phenyl groups. The more
stable structure for the benzothiazole places the R-group hetero-
atom on the same side of the molecule as the oppositely charged
occupied, ranging from entirely
p-bonding across the system at
the bottom of the figure, to fragment orbitals with one node in
the middle of the diagram, to fragment orbitals with two nodes
at the top of the figure.
heteroatom of the oBt fragment. As for
p conjugation, the CRACoBt
Together, the three fragment orbitals of the phenyl group and
five fragment orbitals of the Bt unit combine to create eight occu-
bonds are relatively weak as judged by calculated bond orders as
well as by the bond lengths determined by geometry optimiza-
tions. Such weakness is explained through a molecular orbital
treatment of these systems, which shows that the MOs that con-
pied p-type molecular orbitals, shown in the middle of the figure,
for Ph(oBt). Molecular orbitals 1a00, 2a00, and 3a00 (group theoretical
labels are for the Cs point group) are formed through the combina-
tion of the a2u phenyl fragment orbital with the two most stable
oBt fragment orbitals (i.e., oBt orbitals 1a00 and 2a00). MOs 1a00 and
tain bridging CAC bond
p-bonding character are essentially bal-
anced in number by those that possess p⁄ antibonding character.
Given these computational observations, it would be helpful to
devise a straightforward method that probes how only these two
factors in tandem affect the energetics of this molecular system.
One way to do so is by determining the energy difference between
a planar R(oBt) structure and a corresponding R(oBt) molecule in
which the plane of the R group is perpendicular to that of the
oBt fragment. In this manner, the bridging C atoms maintain their
2a00 have CPhACoBt
p
bonding character, although this character is
predominantly within the Ph and oBt fragments rather than across
the bridging carbon atoms, while MO 3a00 does not have CPhACoBt
p
bonding character. MOs 4a00, 6a00, and 7a00 are nonbonding orbitals
and contain either Ph or oBt character owing to the fact that each
MO is derived from a fragment orbital that has a node that passes
through CPh or CoBt. MOs 5a00 and 8a00 are the CPhACoBt
p
and p⁄
trigonal planarity. The effect of the establishment of a conjugated
system on the CRACoBt bond length can be examined as the R and
oBt rings are fixed in orientations in which their individual sys-
tems are either orthogonal (i.e., no bonding allowed between the
p
combinations of one of the phenyl eg orbitals and the second-high-
est oBt fragment orbital. The occupied CPhACoBt p⁄ antibonding
p
orbital (8a00) effectively cancels out the CPhACoBt
p
bonding compo-
bond that owes its strength
character from MOs 1a00 and 2a00.
p
nent (5a00), leaving a weak bridging
primarily to the
p
two fragments) or co-planar with each other. All other bond
lengths and angles were allowed to optimize. Table 8 summarizes
the results of these calculations. It is important to emphasize that
simply rotating the R group from perpendicular to coplanar with
the oBt unit is meant to be a means of gauging how much each
R(oBt) system is stabilized by the coplanarity of the R and oBt frag-
ments and is not meant to be a representation of the oxidation
reaction itself.
What is particularly remarkable about the data shown in Table
8 is that, with the exception of the values for the two Py(oBt) con-
formers, the molecules that have larger energies of stabilization are
those for which have a greater propensity to undergo oxidation,
especially when the values that correspond to the more stable con-
p
To understand the effect that the electronic occupation of
Ph(oBt) molecular orbital 8a00 has on the system, a geometry opti-
mization was performed on a system that has two fewer electrons.
Although removing two electrons from Ph(oBt) to generate the
dication is one way to do so, it seems more reasonable to use a
neutral molecule to eliminate the effect that a 2+ charge would
have on the system. Therefore, another way to reduce the number
of p-type electrons by two is to replace the SoBt atom with N and to
replace the phenyl group with a cyclopentadienyl. Upon undergo-
ing a geometry optimization, this molecule was found to have a
bridging CAC bond length of 1.37 Å and a calculated NLMO bond
order of 1.69 while the same parameters for Ph(oBt) are 1.47 Å
former for the heteroatom-containing
R group systems are

M.A. Lynn et al. / Journal of Molecular Structure 1011 (2012) 81–93
91
Fig. 11. Molecular orbital diagram of the p-type orbitals of Ph(oBt).
considered. Remembering that these values are only comparisons
of the differences in total energies between R(oBt) structures in
which the R and oBt fragments are either coplanar, these energies
take into account not only the stabilization gained from the forma-
perpendicular conformation to parallel. In line with previous com-
ments here regarding the CRACoBt bond lengths, the compounds
that oxidize the fastest exhibit the largest decrease in this distance
as well as the shortest CRACoBt bond lengths as shown in Table 9.
The CAC bond length shortens the most for Pyr(oBt) (ꢁ0.029 Å)
and for Fu(oBt) (ꢁ0.026 Å), which are the products of the fastest
oxidation reactions, but the magnitude across the entire span of
molecules (0.016–0.029 Å) is quite small. This finding confirms
that the heteroatom-induced electrostatic interactions between
the R and oBt fragments are indeed the primary reason for this
effect.
The most immediate question that arises from the computa-
tional results pertains to the particular order of observed relative
rates of reaction and why there seems to be a discrepancy for the
pyridinyl-substituted analog. Given the factors discussed above,
it seems best to separate these seven compounds into three sepa-
rate classes: (1) systems with R groups that possess either a non-N
heteroatom (R = Fu and Th) or that have a nitrogen that does not
have a lone pair that is capable of having an electrostatic interac-
tion with the H atom on NBt (R = Pyr), (2) systems with R groups
that do not possess a heteroatom in the ring (R = Ph, CF3Ph,
MeOPh), and (3) the system that has an R group possessing a nitro-
gen atom that does have an electron lone pair that can interact
with the NBt H atom (R = Py).
The first group of molecules contains R groups that have hetero-
atoms in the ring: Pyr, Fu, and Th. For these three systems, there is
a definite energy preference for the direction in which the R group
prefers to be oriented in the oxidized compound. As can be seen in
Table 7, these molecules are calculated to have slightly shorter
CRACoBt bonds but the primary structural influence is that each
can establish favorable electrostatic interactions between the
charges on the heteroatoms of the R and oBt fragments.
The second group of molecules contains R groups that do not
have heteroatoms in the ring: Ph(Bt), CF3Ph(Bt), and MeOPh(Bt).
For these three systems, there is no energy preference regarding
the direction in which the R group rotates to become coplanar with
tion of a system-wide conjugated
p system but also the energy that
results from the interaction of the heteroatoms on the R and oBt
groups. For Th(oBt), Fu(oBt), and Pyr(oBt), which are the products
of the faster oxidation reactions, the energies of stabilization range
from 6.50 kcal/mol to 9.47 kcal/mol when the R group is rotated
into the orientation having a more favorable electrostatic interac-
tion or from 5.04 kcal/mol to 6.01 kcal/mol when rotated to the
less favorable configuration. For the R(oBt) systems in which the
R group does not contain a heteroatom within the ring (i.e.,
R = Ph, CF3Ph, MeOPh), the span of energies of stabilization from
5.31 to 5.79 kcal/mol is narrower and the values themselves are
smaller in magnitude than for Th(oBt), Fu(oBt), and Pyr(oBt). Thus,
rotating the R group into the more favorable orientation imparts a
larger energy of stabilization upon those compounds with a het-
erocyclic R group than for any of the systems with a phenyl R
group. Of course, the one compound for which the calculated en-
ergy of stabilization does not correlate with the experimental rel-
ative rate of reaction is the pyridinyl-substituted species. The
energy determined for this molecule is the second highest of the
entire series, which means that this compound would be expected
to have one of the fastest oxidation rates. As will be summarized
shortly, this system must have some other effect that causes the
oxidation reaction to be the slowest of the compounds that we
have examined here.
Despite the nearly doubling of the energy of stabilization from
the phenyl analog to the pyrrolyl-substituted system, as can be
seen in Table 9 there is little change in the CRACoBt bond lengths
either between the perpendicular and coplanar conformations of
a given R(oBt) system or for this difference across the entire span
of molecules. Further evidence of the relatively weak
p bonding
in the CRACoBt bond is the small decrease in bond length (no more
than 0.029 Å) as each R(oBt) system is allowed to convert from a

92
M.A. Lynn et al. / Journal of Molecular Structure 1011 (2012) 81–93
Table 8
the R and Bt/oBt fragments is the primary influence on this
reaction.
Energy of stabilization obtained when geometry of R(oBt) system is converted from
perpendicular to planar.
R
Energy of stabilization to more
stable R(oBt) conformer
(kcal/mol)
Energy of stabilization to less
stable R(oBt) conformer
(kcal/mol)
Acknowledgments
This work was supported by an NTID Faculty Evaluation and
Development Grant (MAL) as well as generous financial support
from Union College (LAT). We also thank the National Science
Foundation (NSF 0521237) for supporting the X-ray diffraction
facility at Vassar College (JMT).
Ph
Py
5.31
9.32
5.39
6.50
2.60
5.04
CF3Ph
Th
MeOPh 5.79
Fu
Pyr
7.67
9.47
5.51
6.01
Appendix A. Supplementary material
CCDC 808288, 809123, 808557 and 809122 contain the supple-
mentary crystallographic data for Ph(Bt), Py(Bt), Ph(oBt) and
Py(oBt) respectively. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif. Supplementary data associ-
ated with this article can be found, in the online version, at
doi:10.1016/j.molstruc.2011.12.001.
Table 9
Optimized CRACoBt bond lengths for perpendicular and coplanar R(oBt) systems.
R
CRACoBt bond length (Å)
Change
Perpendicular
Coplanar
Ph
Py
CF3Ph
Th
MeOPh
Fu
1.485
1.492
1.486
1.471
1.483
1.468
1.469
1.469
1.469
1.470
1.446
1.465
1.442
1.440
ꢁ0.016
ꢁ0.023
ꢁ0.016
ꢁ0.025
ꢁ0.018
ꢁ0.026
ꢁ0.029
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