Charge delocalization from cationic substituents into phenanthrene: Variation in response among regioisomeric carbocations and carboxonium ions

Article abstract of DOI:10.1039/a707423i

In an effort to assess charge delocalization and stabilities, a series of regioisomeric PAH-C⁺R₂ carbocations (PAH = phenanthrene; R = Me, Ph) were generated from their alcohols by ionization with FSO₃H/SO₂ClF.

Full text of DOI:10.1039/a707423i

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Charge delocalization from cationic substituents into phenanthrene:
variation in response among regioisomeric carbocations and
carboxonium ions
Kenneth K. Laali* and Sandro Hollenstein
Department of Chemistry, Kent State University, Kent, OH 44242, USA
؉
In an effort to assess charge delocalization and stabilities, a series of regioisomeric PAH᎐C R
2
carbocations (PAH ؍ phenanthrene; R ؍ Me, Ph) were generated from their alcohols by ionization with
FSO H/SO ClF. Model carboxonium ions were also generated by O-protonation of the isomeric acetyl-
3
2
and benzoyl-phenanthrenes with FSO H/SO ClF. The delocalization paths and the arenium ion character
3
2
in the resulting carbocations and carboxonium ions are evaluated via low temperature NMR studies;
conformational aspects in the carboxonium ions are also addressed. The resulting cations may serve as
models for epoxide ring opening in biologically active dihydro diols of several classes of PAHs for which
the diol epoxide activation path is believed to be significant in cancer induction.
Introduction
importance of various regioisomeric phenanthrene-substituted
carbocations, bearing in mind that these studies merely serve as
a guide to in vivo reactions where ion pairing and nucleophilic
assistance are logically important.
A formidable body of experimental evidence points to the PAH
diol epoxide activation path as the primary reaction pathway
leading to PAH–DNA adduct formation and onset of cell
ϩ
ϩ
ϩ
ϩ
Whereas we have prepared and studied 5 , 6 , 7 and 8 (Fig.
1–6
damage in several classes of PAHs. Involvement of dihydro-
trihydroxy carbenium ions as reactive intermediates in the
metabolic activation of PAH–diol epoxides has been estab-
lished based on numerous solvolytic studies probing the rate,
2
(
) under stable ion conditions via the alcohols 5-OH–8-OH
ϩ
ϩ
Scheme 1), 9 and 10 remain elusive since (i) all attempts to
7–14
stereochemistry and products.
O
HO
CH3
R
We are engaged in direct studies of PAH carbocations and in
charge delocalization mapping at their periphery with the aim
of searching for correlations between the mode of charge
MeLi
Et2O
R
15
delocalization and biological activity. In a rather unique way,
stable ion chemistry allows the ‘bay-region theory’ to be
experimentally tested.
1–4
5-OH–8-OH
Along these lines, our recent studies focused on persistent
16,17
chrysenium and phenanthrenium cations,
regioisomeric
ϩ
18
PyC R (Py = pyrene) carbocations, and on tuning the elec-
2
FSO3H–SO2ClF
tron demand at the carbocation (aryl π-participation) via an
ϩ
19
α-CF in ArC (CF )R carbocations.
3
3
+
O
H
CH3
+
The present study seeks to examine the mode of charge
delocalization (as deduced from the magnitude of ∆δ
C
R
15,20,21
R
values)
in a series of phenanthrene-substituted carbo-
cations and their regioisomeric carboxonium ion analogs, in
order to gauge the degree of π-participation and arenium ion
character depending on the regioisomer. The carbocations and
carboxonium ions studied may be viewed as simplified models
of dihydro diol ring opening in several classes of PAHs.
+
+
5+–8+
1
H –4H
R = CH3, Phenyl
Results and discussion
Scheme 1 Synthesis of the isomeric alcohols; generation of carbo-
cations and carboxonium ions
Relationship to carcinogenesis
Chrysene 1,2-dihydro diol 9a and 3,4-dihydro diol 5a (Fig. 1)
are believed to be the major products of metabolism in rat liver
cells whose metabolic activation gives their corresponding syn-
synthesize 1-acetyl- and 1-benzoyl-phenanthrene led to mix-
tures of 2-, 3- and 9-substituted isomers and (ii) peri-strain in
the bay-region prevents substitution at C-4 by conventional
synthetic means.
6
and anti-diol epoxides (9b/9c and 5b/5c). The 5b isomer has
1
received synthetic attention for biological studies. In the benzo-
For comparison, four examples of persistent carboxonium
[
a]anthracene system, the bay-region (1,2) and K-region (5,6)
ϩ
ϩ
ions of isomeric acetyl- and benzoyl-phenathrenes 1H –4H
epoxides are biologically most important, but other epoxides
22
have been provided (Fig. 2).
including the 8,9-arene oxide 5d have been synthesized. Syn-1
thesis of the triphenylene diol epoxide 7a has been discussed,
but its biological activity has apparantly not been investigated.
The bay-region diol epoxide of benzo[c]phenanthrene 10a is
NMR assignments
Detailed NMR assignments for the α-phenanthrene-substituted
carbocations, their alcohol precursors, protonated acetyl- and
benzoyl-phenanthrenes and their precursors (Tables 1–4) were
5a
highly tumorigenic and has been studied in detail. Simplifying
these structures (Fig. 1) focuses attention on the possible
J. Chem. Soc., Perkin Trans. 2, 1998
897

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OH
OH
OH
OH
HO
HO
HO
HO
OH
O
O
metabolic
activation
and/or
9+
9a
9b
9e+
9c
d+
9
O
O
O
OH
OH
OH
OH
OH
OH
5a
5+
5d
5b
and/or
5c
OH
OH
O
O
OH
OH
7+
6a
6+
7a
OH
HO
O
10a
10+
Fig. 1 Analogy between carbocations formed from diol epoxide metabolites and the carbocations generated in this work
1
13
based on H, C, H/H COSY and C/H HETCOR NMR
spectra. The low field proton resonances of the bay region (H-4
qualitative correlations between NMR shifts and calculated
(semiempirical) charge densities have also been observed in
ϩ
ϩ
21a,23
and H-5, all doublets except H-4 of 2, 2H , 6-OH and 6 ) were
always the starting point of the assignments, which together
with the H/H COSY relationships, allowed the A and C ring
protons to be assigned. In the 9-substituted phenanthrenes a
very small but significant H/H COSY correlation between H-4
and H-10 was used to determine the A and C ring protons. In
some cases a few assignments are still uncertain because of
extensive overlap of the resonances.
The C NMR resonances of the proton-bearing carbons
were assigned with the help of the C/H HETCOR correlations,
whereas the quaternary carbons in the neutral compounds were
assigned according to the substituent effects and by analogy. In
the cations, the calculated charges (AM1) and in particular
changes in Mulliken carbon charges ∆q = q (ion) Ϫ q (neutral)
delocalized polycyclic dianions.
Despite their inherent dif-
ferences, the correspondence between the overall charge pattern
derived from ab initio and AM1 methods in modelling PAH
24
epoxide ring opening (→carbocation) has been shown.
NMR features of the cations (Tables 1 and 3; Fig. 3)
ϩ
ϩ
ϩ
Carboxonium ions. The C–OH resonance in 1H –4H was
only observed at temperatures below Ϫ45 ЊC as a very broad
singlet at ca. δ 13.5. At higher temperatures it broadened
further and disappeared into the base line (probably due to fast
exchange with the solvent acid).
13
ϩ
1H : A low field singlet at δ 9.03 is characteristic for H-1 and
two low field doublets at δ 8.87 and 8.75 for the bay region
13
protons (H-4/H-5) can be observed. In the C NMR spectrum,
the most deshielded aromatic (observed) resonance is for C-4a
(para to the acetyl substituent) at δ 42.1.
c
c
were used as an additional (qualitative) guideline for the
assignments;
not be assigned with certainty. Despite the limitations of semi-
empirical methods in predicting charge densities, good corre-
spondence was previously found between the overall pattern of
1
5–17
13
the quaternary C NMR resonances could
ϩ
1
2H : The H resonance for H-4 appears at very low field
(δ 9.89) due to bay region effects and the ortho acetyl substitu-
ent effect. C-10a (para to the substituent) is the most deshielded
aromatic resonance (δ 143.6) observed.
∆
δC and AM1 charges in a number of PAH carbocations (see
refs. 15–17 and related references cited therein). Reasonable
ϩ
1
ϩ
3H : The most deshielded H resonances in 3H are the H-10
8
98
J. Chem. Soc., Perkin Trans. 2, 1998

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O
CH3
O
H3C
CH3
O
O
1
2
3
4
H
O
CH3
H
+
+
O
H3C
CH3
H
O
O
+
+
H
H+
2H+
3H+
4H+
1
H3C
HO
CH3
HO CH3
H3C
CH3
HO
HO
CH3
CH3
5-OH
6-OH
7-OH
8-OH
H3C
CH3
H3C
+
+
H3C
CH3
CH3
+
+
CH3
5+
6+
7+
8+
Fig. 2 Regioisomeric acetylphenanthrenes and their carboxonium ions; phenanthrene-substituted alcohols and their carbocations
ϩ
ϩ
(
singlet at δ 9.32) and the H-8 (doublet at δ 8.95), whereas the
7 : The most deshielded proton resonances for 7 are the
bay region protons appear at δ 8.73 and 8.88. The most
deshielded ring carbon resonances are the ortho carbon C-10 (at
δ 154.6) and the C4a (at δ 138.7) which is para to the protonated
acetyl substituent.
H-10 (at δ 9.58) and the bay region Hs (at δ 8.77 and 8.82). The
most deshielded ring carbon resonances are for C-10 and C-3
(δ 159.6 and 143.2, respectively).
ϩ
1
ϩ
8 : The H NMR spectrum of 8 is rather complicated due to
ϩ
1
ϩ
4
H : The H NMR spectrum of 4H is very complicated due
extensive overlap of the signals. The bay region protons appear
ϩ
to extensive overlap. The bay region protons (H-4/H-5) are at
δ 8.56 and 8.64 and the characteristic singlet for H-10 is at
δ 8.16 (see also further discussion).
at δ 8.78 and 8.93. For this cation the resonance for C is at
δ 218.9 and the most deshielded aromatic carbon resonance is
the C-10 (δ 158.0).
ϩ
ϩ
Carbocations. 5 : The proton resonances are similar to 1H
but more deshielded. The H-1 singlet is at δ 9.39 and the bay
region protons are at δ 8.93 and 8.87. The most deshielded ring
AM1 calculations
AM1 calculated changes in carbon charges ∆q = qC(ion)
Ϫ
ϩ
carbon resonance is observed at δ 148.4 and the C is at δ 238.5.
qC(neutral) qualitatively support the overall mode of charge
delocalization as deduced based on ∆δC values. Thus AM1-
predicted charge alternation paths are generally the same as
those deduced based on NMR experiments, except for C-7 in
ϩ
6
: The very low field singlet at δ 10.08 was unambigously
assigned to the bay region proton which is also ortho to the
carbocation center. The other bay region proton is observed at
ϩ
ϩ
ϩ
ϩ
ϩ
δ 8.90. In 6 , the carbocation center has a chemical shift of
3H , 4H , 7 and 8 , where the calculated charges are much
higher than the observed chemical shifts would suggest (see
earlier comments on the use of semiempirical methods).
δ 234.7 and the most deshielded ring carbon atom is C10a
(
δ 148.2, para to the substituent).
J. Chem. Soc., Perkin Trans. 2, 1998
899

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1
Table 1 H NMR data for the carboxonium ions and carbocations
a
Chemical shift (ppm)
ϩ
ϩ
ϩ
ϩ
ϩ
ϩ
ϩ
ϩ
H-atom
1H
2H
3H
4H
5
6
7
8
1
2
3
4
5
6
7
8
9
9.03
—
8.16
8.45
—
8.24
7.88
8.15
8.72
8.80
7.91
7.91
8.95
—
7.67–7.83
7.67–7.83
7.94
8.56
8.64
7.67–7.83
7.67–7.83
8.32
—
8.16
9.39
—
7.97
8.54
—
8.42
7.93*
8.36
8.77
8.82
7.99*
7.99*
8.31
—
9.58
3.46
3.47
—
8.13–8.18
7.82*
8.13–8.18
8.78
8.42
8.87
8.75
7.89
7.85*
8.02*
7.99*
7.89*
3.38
8.60
8.93
8.87
7.91
8.07*
8.02*
8.07*
8.07*
3.47
9.89
8.85
7.93
7.86
8.08
8.26
7.93
3.45
10.08
8.90
8.04
7.91
8.14
8.54
8.16
3.42
3.54
—
8.83
7.86–8.00
7.86–8.00
7.86–8.00
—
8.05
3.78
1
0
CH3
9.32
3.46
—
3
.50
Ph(ortho)
Ph(meta)
Ph(para)
—
—
—
—
—
—
—
—
—
8.10
7.89
7.63–7.83
—
—
—
8.13–8.18
7.86–8.00
8.32
—
—
—
—
a
*
= Assignment may be interchanged (within same molecule).
1
Table 2 H NMR data for the precursors
a
Chemical shift (ppm)
H-atom
1
2
3
4
5-OH
6-OH
7-OH
8-OH
1
2
3
4
5
6
7
8
9
8.41
—
7.90
8.11
—
7.93
7.63
7.74
8.65
8.69
7.68*
7.68*
8.74
—
8.17
2.82
—
—
—
7.78
7.48–7.63
7.48–7.63
8.61
8.65
7.48–7.63
7.48–7.63
8.05
—
7.76
—
7.87
7.38
~7.5
8.00
—
7.86
7.74
—
7.86
7.59
7.63
8.64
8.75
7.65*
7.65*
8.93
—
7.82
1.91
—
—
—
7.98
7.64
7.69
8.67
8.70
7.50
~7.3
7.98
—
8.15
2.15
7.46
~7.3
~7.2
8.13
8.63
8.62
7.65
7.65
7.88
7.75
7.75
2.75
—
7.78
8.65
8.67
7.60
7.66
7.90
7.75
7.75
1.72
—
9.28
8.75
7.73
7.64
7.90
7.82*
7.66*
2.78
—
8.90
8.79
7.70*
7.66*
7.92
7.74
7.74
1.76
—
1
0
CH3
Ph(ortho)
Ph(meta)
Ph(para)
—
—
—
—
—
—
—
—
a
*
= Assignment may be interchanged (within same molecule).
13
Table 3
C NMR data for the carboxonium ions and carbocations
a
Chemical shift (ppm)
ϩ
ϩ
ϩ
ϩ
ϩ
ϩ
ϩ
ϩ
C-atom
1H
2H
3H
4H
5
6
7
8
1
2
3
4
4
4
5
6
7
8
8
9
0
n.o.
b
n.o.
131.8
n.o.
d
n.o.
d
135.1
129.7
138.7
124.2
138.7
h
124.8
130.1
131.2
127.6
h
129.5*
128.9*
133.1
123.4
148.0
i
124.0
129.5*
129.5*
126.2
i
148.2
c
132.6
126.9
148.4
j
127.6
129.8
135.8
129.5*
c
132.0*
130.4*
j
127.7
132.7
e
141.8
129.8
e
123.4
132.4
130.6
131.8
e
146.5
132.6
148.2
234.7
31.3
31.9
—
139.1
130.1*
143.2
124.3
f
137.0
130.1*
139.0
124.4
g
126.1
142.1
b
125.7
128.0
132.5
130.1*
b
131.2*
129.2*
b
216.0
24.8
a
b
d
k
l
123.3
130.4
129.9
130.6
d
138.7
126.9
143.6
215.3
24.9
125.2
130.8*
130.9*
129.0
f
125.1
130.5*
131.3*
129.6*
l
a
h
i
k
g
1
1
154.6
h
214.4
26.8
141.7
i
207.6
—
159.6
k
230.1
31.1
35.5
—
—
—
—
158.0
l
218.9
—
0a
COH /C
CH3
ϩ
ϩ
238.5
31.7
3
—
—
—
—
2.1
Ph(ipso)
—
—
—
—
—
—
—
—
—
—
—
—
i
l
Ph(ortho)
Ph(meta)
Ph(para)
136.3
130.6
134.5
—
—
—
139.7
131.7
145.3
a
b
c
d
*
= Assignment may be interchanged (within same molecule); n.o. = not observed. 136.4, 131.1, 129.5, n.o. 138.9, 137.4. 133.3, 131.8, 130.5,
e f g h i j k
1
1
29.2. 135.9, 133.1, 132.1. 142.8, 142.3. 145.0, 138.3. 131.3, 129.6, 127.1, 125.2. 135.0, 131.9, 128.8, 127.4, 125.1. 133.0, 129.2. 131.2, 129.6,
l
27.9. 132.1, 130.3, 130.0, 125.4.
9
00
J. Chem. Soc., Perkin Trans. 2, 1998

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13
Table 4
C NMR data for the precursors
a
Chemical shift (ppm)
C-atom
1
2
3
4
5-OH
6-OH
7-OH
8-OH
1
2
3
4
4
4
5
6
7
8
8
9
0
129.7
b
125.0
123.0
b
128.8
125.3
c
123.8
c
129.7
127.0
128.9
122.6
d
129.1
127.1*
128.2*
122.6
e
123.6
147.3
123.7
122.7
f
128.4
123.6
147.2
117.6
g
128.9
126.6*
126.7*
122.2
h
129.5*
127.2
127.4
122.8
i
a
b
b
c
d
e
f
g
h
i
123.2
126.9*
127.6*
128.6*
b
127.7*
127.2*
b
197.8
26.6
—
—
—
122.6
126.2
127.1
128.8
c
129.6*
127.2*
c
198.1
26.8
—
—
—
122.7
127.5*
127.0*
126.7
d
134.6
130.6
d
201.8
29.9
—
—
—
122.9
127.1*
127.1*
126.5
e
138.1
129.4
e
197.8
—
135.2
130.3
128.4
133.3
122.6
126.4
126.5
128.5
f
127.1*
127.0*
128.5
72.6
31.8
—
122.6
126.6*
126.4*
128.5
g
126.4*
126.4*
g
72.9
31.8
—
—
—
123.2
125.8*
125.8*
128.1
h
141.2
123.7
h
73.9
31.4
—
—
—
123.4
126.2
126.2*
128.7*
i
148.5
125.7
i
77.0
—
140.3
125.5
128.8
127.2*
a
1
1
0a
C᎐O
᎐
CH3
Ph(ipso)
Ph(ortho)
Ph(meta)
Ph(para)
—
—
—
—
—
—
—
—
a
b
c
d
*
= Assignment may be interchanged (within same molecule). 134.7, 133.2, 132.8, 131.2, 129.6. 134.8, 134.7, 132.1, 130.6, 129.7. 131.9, 130.7,
e
f
g
h
i
1
29.8, 128.2. 131.2, 130.5, 130.1, 130.0. 131.9, 131.8, 130.1. 132.1, 130.6, 130.3, 129.8. 131.5, 131.0, 130.1, 129.9. 132.1, 131.3, 130.9, 130.0.
ϩ
ϩ
ϩ
ϩ
Table 5 Magnitude of carbon deshielding values in carboxonium ions
3H /4H and 7 /8 indicates that the phenyl group reduces
and carbocations
phenanthrenium ion character, whereby additional stabilization
is gained by delocalization into the phenyl group in 4H and 8
as compared to the methyl groups in 3H and 7 .
ϩ
ϩ
ϩ
∆
δ C᎐O H/
Σ∆δ (arom.)
C
᎐
C
ϩ
ϩ
C᎐O (ppm)
᎐
(ppm)
ϩ
ϩ
ϩ
ϩ
1
2
3
4
H
H
H
H
ϩ18.2
a
a
Stabilization of the positive charge depending on substitution
ϩ17.2
ϩ12.6
ϩ9.6
If one compares the NMR characteristics of the regioisomeric
2,3,9) α-phenanthrene-substituted carbocations and carbox-
ϩ51.1
ϩ28.3/ϩ21.0
(
b
onium ions with each other, it becomes apparent that the
delocalization of the positive charge into the phenanthrene
ϩ
∆
δ C /
Σ∆δ (arom.)
(ppm)
C
C
ϩ
ϩ
ϩ
ϩ
moiety is best in the 9-substituted cases (3H , 4H , 7 and 8 ),
COH
ϩ
ϩ
followed by the 3-substituted cations (2H and 6 ). Charge
delocalization into the phenanthrene moiety via the 2-position
ϩ
ϩ
ϩ
ϩ
5
6
7
8
165.9
161.8
156.2
141.9
ϩ79.6
ϩ82.5
ϩ91.3
ϩ54.1/44.1
ϩ
ϩ
(
as in 1H and 5 ) is least effective (see Table 5). Thus the ∆δ
C
values for the carbonyl carbon in the carboxonium ions
b
ϩ
ϩ
decrease from 1H to 4H , indicative of increased oxonium
a
13
b
ion character. The same order is observed in the carbocations
Not all C resonances were observed in the carbocations. Phen-
anthrene carbons/phenyl carbons.
ϩ
ϩ
ϩ
ϩ
5 –8 , where the ∆δ
values for the C center decrease from 5
C
ϩ
ϩ
to 8 , showing that carbocation 5 is least delocalized where-
as 8 is most effectively delocalized. At the same time, the
ϩ
A comparative discussion of carboxonium ions and the
carbocations
The magnitude of charge delocalization into the phenanthrene
system is much larger in the carbocations 5 –8 than in the
carboxonium ions 1H –4H . The C chemical shifts of
the aromatic carbons of the cations 5 –8 are much more
deshielded (ca. 40 ppm) as compared to 1H –4H , which is in
agreement with the oxonium ion character of 1H –4H .
chemical shifts of the aromatic carbons in the 9-substituted
phenanthrenes are more deshielded than in the 3-substituted
cases, which are in turn more deshielded than the 2-
ϩ
ϩ
ϩ
ϩ
13
substituted phenanthrenes. The increase in Σ∆δ values for
C
ϩ
ϩ
ϩ
ϩ
ϩ
ϩ
the aromatic carbons from 1H to 4H and 5 to 8 clearly
indicate that the stabilization of the positive charge is most
effective in the 9-substituted cations and least effective in the
ϩ
ϩ
ϩ
ϩ
2
-substituted analogs.
The charge alternation path in different substituted
phenanthrenes
؉
Conformational aspects related to rotation around C ᎐C(ipso)
and (HO ᎐C)᎐C(ipso) bonds
؉
The charge alternation modes for the 2-, 3- and 9-substituted
phenanthrenes are totally diverse. In the 2-substituted cations
Due to the delocalization of the positive charge into the phen-
ϩ
ϩ
ϩ
ϩ
1
H and 5 , the delocalization path is mainly centered around
anthrene system, the C ᎐C(ipso) and (HO ᎐C)᎐C(ipso) bonds
show significant double bond character. The CH groups in
ring A and C and the most deshielded aromatic carbon is C-4a
3
ϩ
ϩ
ϩ
(
6
para to the substituent). In the 3-substituted cations (2H and
), the charge is localized in ring A and B with C-10a being the
carbocations 5 –7 are nonequivalent. Even at room temper-
ature the methyl groups of 7 remain non-equivalent, indicative
of a large rotational barrier. On the other hand, in the
protonated cations 1H and 2H , we can observe two different
isomers only at ca. Ϫ70 ЊC (see Fig. 3). By warming the
samples, the rotation around the (HO ᎐C)᎐C(ipso) bond
becomes faster and at Ϫ20 ЊC just an averaged conformation is
observed. The two rotational isomers (ratio ca. 2:1) could not
be individually identified and the assignment of the chemical
ϩ
ϩ
most deshielded (para to the substituent). In the 9-substituted
cations the positive charge is mostly localized on the A and B
rings, but with C-10 as the most deshielded carbon (ortho to the
acetyl substituent). In all cases, the protonated ketones show
the same delocalization path as the carbocations, but the
arenium ion character is significantly lower (smaller ∆δs). The
comparison between the two pairs of 9-substituted cations
ϩ
ϩ
ϩ
J. Chem. Soc., Perkin Trans. 2, 1998
901

View Article Online
H
+
0.63
H3C
O+
1.8 +18.2
+0.34
H
+0.25
H
H
+
O
-
+
17.2
+0.26
+2.7
+
0.41
H
H +0.31
+5.4
+
0.29 H
H +0.62
H
+
0.67 H3C
-
+3.0
+
9.8
1.9
+
3.1
+1.6
H+0.27*
H+1.15
+24.0
H +0.14
2.0*
+
0.24H
+0.61 H
+0.07 H
+
+
-0.3*
9.1*
H+0.44*
+
0.64
+
3.5*
H+0.24*
+
0.13
H
+0.10
H
+0.11
H
CH
3
-3.1
+
2.5
1.1*
0.24 H
+0.7
+4.2
+2.1
+O H
+
+1.5*
+1.8
H+0.18
+2.6*
+0.9
+12.6
H+0.14*
+0.20 H
+
0.23*
H
H
+
+
4.9*
+2.8
+4.2*
+0.21
H
H
H
+
+
0.20*
+0.22
0.23*
H+ (1)
2H+ (2)
3H+ (3)
1
-
0.1
+
0.3
+
0.19/-0.35
H
1
.75
+0.1
-0.5
CH
H C
+
CH
3
+161.8
+0.80
1.78
3
H
+
165.9
+
1.8*
-0.11/+0.05
H
3+9.1
+
0.31/+0.46 H
4.9*
0.8
0.05 H
+
0.82 H
H+1.39
+24.6
H+0.11
+
1.66
+
+
+0.4*
+1.78 H C
+
8.9
3
-0.7
+
+0.40
H
+0.13/+0.33
H
+
4.2
+34.2
-
H+0.32*
3.4*
+4.9
H+0.32*
H+0.42
+6.2*
+20.1*
H+0.80
+
0.28 H
+1.18 H
+
12.3
+1.2
+
+
2.2
-0.01
H
+
0.20 H
+0.11 H
+0.8
+5.8
+0.34* H
+
9.8
H
+
1.1
2.4*
0.19/+0.35 H
+6.0
+0.51
+
+
5.0
3.4
+
-0.3
+ O
H
+0.23
H
+1.0*
+3.3
H+0.22
+
H
+
2.4*
+0.31 H
H+0.12*
+
0.27
+9.3
+
4.2*
H
+
0.19/+0.35
H
H
+0.25
+
0.41*
4
H+ (4)
5+
6+ (6-OH)
(5-OH)
+
0.33*
+
0.18*
H
H
+
3.5*
+
2.9*
+0.15/+0.20
H
+
0.73 H
16.5*
2.1
H +0.56
+10.2
+
0.44/+0.49 H
+
+
11.6
1.6
0.09 H
+7.5*
+
+
-0.10
1.12
H+1.76
35.9
+
0.13 H
H
H
+
+
+1.55
1.56
+
32.3
18.1*
+
2
.9
+
0.07 H
CH3
+
0.13 H
+
+
H
+0.56/+0.70
+
2.0
5.0*
0.34* H
+141.9
+14.2
+
1.7
CH
3
+
+0.9
+
+
0.3 +156.2
4.1
+4.3*
+0.9*
CH3 H +0.67/+0.72
-1.2
+1.63
+
H
+
0.36/+0.50 H
H
+
5.1*
-0.62
+
5.1*
+0.32/-0.02
H
H
+
0.34*
+
0.56/+0.70
7+
(7-OH)
8+
(8-OH)
Fig. 3 The ∆δ and ∆δH values in the carbocations and carboxonium ions; * means one of the two or both δ values were derived from chemical shifts
C
ϩ
ϩ
that were interchangeable (for 4H and 8 double figures refer to max. and min. possible values)
؉
؉
shifts was only possible for the averaged structure at Ϫ20 ЊC.
Except for the two ortho-carbons which could not be observed
Structural features in 4H and 8 carbocations
An interesting observation was made by comparing the H-10
proton chemical shifts in the 9-substituted phenanthrene carb-
oxonium ion and carbocation. For 3H the H-10 chemical shift
is at δ 9.32 whereas in 4H this proton is only at δ 8.16. The
difference between the H-10 chemical shifts in 7 (δ 9.58) and 8
(δ 8.05) is even larger. Its origin is not merely the fact that the
(
probably due to broadening), all other carbon and proton
ϩ
resonances which were split at lower temperature clearly
ϩ
merged at Ϫ20 ЊC.
ϩ
ϩ
ϩ
In protonated 9-acetyl- and 9-benzoyl-phenanthrene (3H
ϩ
and 4H ) only one of the possible isomers is detected at Ϫ70 ЊC
ϩ
ϩ
(
Scheme 2). This observation confirms the AM1 calculated
phenyl groups in 4H and 8 stabilize more positive charge than
the methyl groups do in 3H and 7 . The C-10 carbon reson-
o
ϩ ϩ
energies for the two different isomers. The ∆H values for the
non-observed isomers are 1.0–1.5 kcal mol higher than the
f
Ϫ1
ϩ
ances for example do not show such a big difference (3H :
ϩ
ϩ
ϩ
experimentally observed isomer, whereas the energy difference
between the two geometrical isomers in the 2- and 3-substituted
cations is only ca. 0.3 kcal.
δ 154.6; 4H : δ 141.7; 7 : δ 159.6; 8 : δ 158.0). The unusual
proton shielding is apparently due to transannular shielding of
the phenyl group. In the AM1-calculated minimized structures
ϩ
ϩ
for 4H and 8 , H-10 is located right above the phenyl group (in
syn/anti Protonation
both cases). Such transannular effects could explain the 1–1.5
ppm shielding of H-10 in 4H and 8 as compared to the
methyl analogs.
ϩ
ϩ
Additional splitting of the signals due to a possible syn or anti
protonation of the carbonyl group in the carboxonium ions was
not observed, either because the difference in energy between
the two isomers is too small or because the exchange is too fast.
AM1 calculated relative energies of the two possible isomers
Diol epoxide ring opening
Charge delocalization into the phenanthrene system in the
model arenium ions and carboxonium ions is most effective
(
syn/anti protonation) showed a difference of about 0.1 kcal
Ϫ1
mol .
from the meso position. Based on the magnitude of ∆δ , the
C
9
02
J. Chem. Soc., Perkin Trans. 2, 1998

View Article Online
H
O
H
tially all be important en route to PAH–DNA adduct formation
and onset of cell damage! Our simple model studies have not
taken into account the role of DNA and issues pertaining to
DNA base-sequence selectivity, steric/conformational effects
and repair. In future work, we hope to draw a biological parallel
by examining the DNA-binding ability of the regioisomeric
alcohols 5-OH–8-OH in cells in culture.
CH3
H3C
O+
+
Experimental
NMR spectroscopy
NMR spectra were recorded on a GE GN-300 wide bore
instrument. The NMR spectra of the precursors were recorded
H
+
O
CH3
H3C
H
O
at room temperature using CDCl as solvent (δ 7.26, δ 77.0).
3 H C
+
The cation spectra were obtained at temperatures between Ϫ20
and Ϫ80 ЊC; CH Cl was used as internal standard (δ 5.32, δ
2
2
H
C
5
3.8). Copies of the C/H HETCOR spectra for the carbo-
ϩ ϩ ϩ ϩ
cations 7 , 8 , 5 and 6 , C/H HECTOR spectra for the car-
boxonium ions 4H , 1H and 2H and the H/H COSY and
ϩ
ϩ
ϩ
13
C
ϩ
NMR spectra for 3H (9 pages) are available as supplementary
material (SUPPL. NO. 57362). For details of the Supplemen-
tary Publications Scheme see ‘Instructions for Authors’,
J. Chem. Soc., Perkin Trans. 2, available via the RSC Web page
(
http://www.rsc.org/authors).
+
Materials
CH3
H
O
H
Phenanthrene, 2-, 3- and 9-acetylphenanthrene 1–3, methyl-
lithium, benzoyl chloride and AlCl (all Aldrich) were used
without further purification. FSO H (Allied) was purified by
O
CH3
3
+
3
double distillation at atmospheric pressure under argon.
not observed
26
SO ClF was prepared by a modified procedure of Reddy et al.
2
from SO Cl , ammonium fluoride and CF CO H (Aldrich).
2
2
3
2
Several distillation provided pure SO ClF.
2
Synthesis
+
9-Benzoylphenanthrene 4.† A mixture of benzoyl chloride
O
H
(3.26 ml, 36 mmol) and AlCl (4.29 g, 33 mmol) was heated
3
until a clear solution resulted. The mixture was cooled to room
temperature and 24 ml of anhydrous CS was added, followed
by phenanthrene (5 g, 28 mmol) which was added slowly over a
2
O
+
H
2
0 min period (HCl evolution). After an additional 20 min, the
not observed
mixture was cooled in an ice bath, the precipitate was collected
and decomposed by adding a mixture of ice and 10  HCl to
Scheme 2 Rotational isomers
give a dark brown solid. After extraction with Et O (3×) the
2
combined organic layer was washed with saturated aqueous
NaHCO and ice water, and dried (MgSO ). Evaporation of the
solvent resulted in a brown oil which was purified twice by
ϩ
ϩ
ϩ
ϩ
delocalization sequence 7 (8 ) > 6 > 5 can be deduced for
the carbocation intermediates, whose involvement in the diol
epoxide ring opening process has been inferred based on previ-
3
4
column chromatography [pentane–Et O (10:1) and hexane–
2
ϩ
ϩ
ous kinetic and solvolytic studies. Since 9 and 10 could not be
generated and studied for comparison, we resorted to AM1
calculations for a general idea of the relative stabilities based on
Hf values: AM1 predicted that 6 and 5 should have very
close energies (within 1 kcal mol ) and that 9 should be more
chloroform (10:1)] to give 5.4 g of a slightly yellow oil (64%)
(for NMR data, see Tables 2 and 4).
General procedure for the synthesis of the alcohols 5-OH–
0
ϩ
ϩ
∆
8-OH. The ketones 1–4 (ca. 0.5–1.5 mmol) were dissolved in
Ϫ1 ϩ
anhydrous Et O (50–100 ml) under argon. A 5–10-fold excess of
2
ϩ
Ϫ1
stable than 7 by ca. 2.5 kcal mol . Moreover, the correspond-
methyllithium (ca. 1.4  in Et O) was slowly added at room
2
ϩ
ing cyclic carbocation 9e is predicted to be more stable than
temperature, and the solution was stirred for 2–4 h. The reac-
tion mixture was cooled in an ice bath and 100–200 g of ice was
carefully added to the solution. The aqueous layer was
ϩ
Ϫ1
7
b by ca. 1 kcal mol . Whereas the predicted charge delocaliz-
ϩ ϩ
ation pattern for 9 and 6 is very similar, the cyclic analoϩg
exhibits greater arenium ion character and increased Phen᎐C
bond order (1.39 vs. 1.37 Å).
extracted three times with Et O and the combined organic layer
2
was washed with ice water and ice cold brine, and dried over
Earlier studies have suggested that methylated PAHs may
be converted to PAH᎐CH OH derivatives which are then
transformed into esters, which can produce PAH᎐CH2 carbo-
MgSO . After evaporation of the solvent, the slightly yellow
4
2
alcohols 5-OH–8-OH were purified by column chromatography
ϩ
[pentane–Et O (5:1–2:1)] to give the colorless solid products
2
cations. Carcinogenicity in methylated PAHs appears to correl-
ate with the stability of arylmethyl carbocations, for instance
(yields 87–93%) (for NMR data, see Tables 2 and 4).
GC–MS analysis of the alcohols.—GC–MS analysis of 5-
25
ϩ
6
-methylbenzo[a]pyrene is more potent than BaP. In the pres-
OH–8-OH gave in all cases the expected M (m/z 236). How-
ent study, based purely on the NMR studies of the persistent
model carbocations, the potency order 7a > 6a > 5b may be
predicted for the diol epoxides, but taking into account the
predicted close relative energies of the carbenium ions in an
expanded isomeric set, it may be argued that they can poten-
ever, the most abundant fragment cation formed in the gas
†
The literature procedure (P. H. Gore, J. Org. Chem., 1957, 57, 135)
describes the synthesis of 1-benzoylphenanthrene in 19% yield, but we
observed only the 9-substituted isomer.
J. Chem. Soc., Perkin Trans. 2, 1998
903

View Article Online
ϩ
phase was the hydroxy carbocation ArC(Me)OH (m/z 221),
and D. M. Jerina, J. Am. Chem. Soc., 1976, 98, 2965; P. Y. Bruice,
T. C. Bruice, H. Yagi and D. M. Jerina, J. Am. Chem. Soc., 1976, 98,
ϩ
with the relative abundance of ArC(Me)2 ions (m/z 219) being
2
1
973; N. T. Nashed, J. M. Sayer and D. M. Jerina, J. Am. Chem. Soc.
993, 115, 1723.
N. T. Nashed, S. K. Balani, R. J. Loncharich, J. M. Sayer, D. Y.
Shipley, R. S. Mohan, D. M. Whalen and D. M. Jerina, J. Am.
Chem. Soc., 1991, 113, 3910.
almost negligible.
General procedure for stable ion generation. In a typical
experiment, about 30 mg of 1–4 or 5-OH–8-OH was placed in a
mm NMR tube. The NMR tube was then connected to the
8
5
high vacuum line (ace-thread port). After several cycles of
evacuation and flushing with argon, the NMR tube was evacu-
9 N. T. Nashed, A. Bax, R. J. Loncharich, J. M. Sayer and D. M.
Jerina, J. Am. Chem. Soc., 1993, 115, 1711.
1
0 N. T. Nashed, T. V. S. Rao and D. M. Jerina, J. Org. Chem., 1993, 58,
ated for 5 min. About 0.3 ml of SO ClF was then condensed
2
6
344.
into the NMR tube, which was cooled to liquid nitrogen tem-
1
1 H. Yagi, J. M. Sayer, D. R. Thakker, W. Levin and D. M. Jerina,
perature. After completion of the SO ClF addition, the liquid
2
J. Am. Chem. Soc., 1987, 109, 838.
12 J. W. Keller, N. G. Kundu and C. Heidelberger, J. Org. Chem., 1976,
41, 3487.
3 M. D. Hylarides, T. A. Lyle, G. H. Daub and D. L. van der Jagt,
J. Org. Chem., 1979, 44, 4652.
4 D. L. Whalen, N. B. Islam, S. C. Gupta, J. M. Sayer and D. M.
Jerina, in Polynuclear Aromatic Hydrocarbons, Measurements,
Means and Metabolism, ed. M. Cooke, K. Loening and J. Merritt,
Battelle Press, Columbus, 1991, pp. 1021–1035.
15 Review: K. K. Laali, Chem. Rev., 1996, 96, 1873.
6 K. K. Laali, S. Hollenstein, R. G. Harvey and P. E. Hansen, J. Org.
Chem., 1997, 62, 4023.
7 K. K. Laali, S. Hollenstein and P. E. Hansen, J. Chem. Soc., Perkin
Trans. 2, 1997, 2207.
nitrogen bath was exchanged for a dry ice–acetone bath and
about 0.05 ml of FSO H was carefully added under argon.
3
1
After vigorous stirring at Ϫ78 ЊC (vortex) the color of the pro-
ϩ
ϩ
tonated ketone solutions (1H –4H ) turned orange–red and
1
ϩ
ϩ
the carbocation solutions (5 –8 ) turned deep red. About 0.1
ml of CD Cl was slowly added under argon and the cold
2
2
sample was thoroughly mixed (vortex) to give clear homo-
geneous solutions.
1
AM1 calculations
AM1 calculations and energy minimizations were performed
with the HYPERCHEM package (HYPERCUBE 1993).
1
1
1
8 K. K. Laali and P. E. Hansen, J. Org. Chem., 1997, 62, 5804.
9 K. K. Laali, M. Tanaka, S. Hollenstein and M. Cheng, J. Org.
Chem., 1997, 62, 7752.
Acknowledgements
Support of our work on reactive intermediates of carcino-
genesis of PAHs by the NCI of NIH (R15CA63595) is grate-
fully acknowledged.
2
0 Reviews: (a) M. Rabinovitz and Y. Cohen, Tetrahedron, 1988, 44,
6
944; (b) M. Rabinovitz, Top. Curr. Chem., 1988, 148, 99; (c)
K. Mullen, Chem. Rev., 1984, 84, 603.
1 (a) Y. Cohen, J. Klein and M. Rabinovitz, J. Am. Chem. Soc., 1988,
2
1
10, 4634; (b) K. Mullen, T. Meul, P. Schade, H. Schmickler and
E. Vogel, J. Am. Chem. Soc., 1987, 109, 4992; (c) B. Eliasson,
D. Johnels, I. Sethson and U. Edlund, J. Chem. Soc., Perkin. Trans.
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Paper 7/07423I
Received 14th October 1997
Accepted 30th January 1998
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04
J. Chem. Soc., Perkin Trans. 2, 1998