Charge Delocalization Pathways in Persistent 1-Pyrenyl-, 4-Pyrenyl-, and 2-Pyrenylmethylcarbenium Ions as Models of PAH-Epoxide Ring Opening: NMR Studies in Superacids and AMI Calculations

Article abstract of DOI:10.1021/jo9707343

The relative stability, magnitude, and mode of charge delocalization into the pyrene moiety (Py) were evaluated for a series of tertiary and secondary 1-pyrenylmethylcarbenium ions PyC⁺R₁R₂ and PyC⁺R₃

Full text of DOI:10.1021/jo9707343

5804
J . Org. Chem. 1997, 62, 5804-5810
Ch a r ge Deloca liza tion P a th w a ys in P er sisten t 1-P yr en yl-,
4-P yr en yl-, a n d 2-P yr en ylm eth ylca r ben iu m Ion s a s Mod els of
P AH-Ep oxid e Rin g Op en in g: NMR Stu d ies in Su p er a cid s a n d
AM1 Ca lcu la tion s§
Kenneth K. Laali*,† and Poul Erik Hansen*,‡
Department of Chemistry, Kent State University, Kent, Ohio 44242, and Department of Life Sciences
and Chemistry, Roskilde University, DK-4000 Roskilde, Denmark
Received April 24, 1997X
The relative stability, magnitude, and mode of charge delocalization into the pyrene moiety (Py)
were evaluated for a series of tertiary and secondary 1-pyrenylmethylcarbenium ions PyC+R1R2
and PyC+R3H (with R1 ) R2 ) Me and Ph; R3 ) Me, Ph, CH2Ph, and (CH2)10Me), 4-pyrenylmeth-
ylcarbenium ions (with R1 ) R2 ) Me; R3 ) Me and Ph), and 2-pyrenylmethylcarbenium ions (with
R1 ) R2 ) Me). The carbocations were generated from the corresponding carbinols by protonation
with FSO3H/SO2ClF. The primary 1-pyrenyl- and 2-pyrenylmethyl cations could not be generated
by ionization of their primary alcohols. Within the tertiary and the secondary carbocations, π-charge
delocalization into the pyrene moiety and the pyrenium ion character of the resulting carbocations
increase in the order: 1-pyrenyl (R) > 4-pyrenyl (Râ) > 2-pyrenyl (â). The NMR characteristics of
the resulting ions are discussed and compared. The connection between charge delocalization/
stability in the regioisomeric pyrenylmethyl carbocations and the magnitude of carcinogenic activity
in the benzannelated pyrenes, for which the bay-region diol-epoxides are the ultimate carcinogens,
are discussed.
In tr od u ction
Early theoretical studies indicated increased stability
for the bay-region dihydrotrihydroxycarbenium ions rela-
tive to their epoxides. Hu¨ckel and INDO calculations
were carried out on the formation and delocalization
energies of various PAH-carbocations.15,16
Whereas the need for more direct studies of suitable
model PAH-carbocations has been realized, model PAH-
CH2X compounds bearing efficient leaving groups (like
nitrosourea f -N2+) as precursors of arylmethylcarbe-
nium ions proved to be too reactive for relative solution
stability studies.17 Interestingly the carbinols themselves
may become active enzymatically via their corresponding
chlorides18,19 or sulfuric acid esters.19-21
Our work in mechanistic carcinogenesis has been
concerned with generation and NMR studies of arenium
ions of various classes of PAHs, having a varied degree
of carcinogenic/mutagenic activity, with the aim of de-
lineating their charge delocalization pathways and its
modulation by substituents such as nitro and fluoro.22-27
In the present study we have generated from their
carbinol precursors a series of regioisomeric tertiary and
Bay-region diol-epoxides have been identified as the
ultimate metabolic carcinogens in several classes of
polycyclic aromatic hydrocarbons (PAHs) en route to
PAH-DNA adduct formation.1-6
The carbocationic character of the epoxide ring-opening
process has been established in several solvolytic studies
probing the rate, stereochemistry, and products.7-14
† Kent State University.
‡ Roskilde University.
§ Dedicated to Prof. George Olah on the occasion of his 70th birthday.
X Abstract published in Advance ACS Abstracts, August 1, 1997.
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Carcinogenicity; Cambridge University Press: Cambridge, U.K., 1991.
(2) Levin, W.; Wood, A.; Chang, R.; Ryan, D.; Thomas, P.; Yagi, H.;
Thakker, D.; Vyas, K.; Boyd, C.; Chu, S.-Y.; Conney, A.; J erina, D.
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5576.
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nuclear Aromatic Hydrocarbons: Measurements, Means and Metabo-
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S0022-3263(97)00734-2 CCC: $14.00 © 1997 American Chemical Society

Charge Delocalization in Pyrenylmethylcarbenium Ions
J . Org. Chem., Vol. 62, No. 17, 1997 5805
F igu r e 1. Carbinol precursors.
secondary methylcarbenium ions bearing 1-pyrenyl,
4-pyrenyl, and 2-pyrenyl substitutents. Charge delo-
calization into the pyrene moiety has been evaluated on
the basis of the magnitude of the ∆δC-13’s and the
chemical shift of the cation center.
We show that for both tertiary and secondary 1-pyre-
nylmethylcarbenium ions the positive charge is most
effectively delocalized. Thus the pyrenium ion character
of the resulting benzylic carbocations increases in the
order 1-pyrenyl > 4-pyrenyl > 2-pyrenyl.
AM1 charges and energies for representative regio-
isomeric pyrenylmethylcarbenium ions and related mod-
els more closely resembling the PAH-epoxide ring open-
ing intermediates have been calculated for comparison
with experiment. The relationship between carbocation
stability and carcinogenic activity is also addressed.
C+H, respectively; C-3a is then assigned by default. The
NMR data are summarized in Figures 3 and 4.
Ter tiar y 1-P yr en ylm eth ylcar ben iu m Ion s 1a+ an d
2a + (Figures 3 and 4 and Table 1). Distinctly different
colors are observed for these carbocations (Table 1). The
C+ center in 2a + is 9.88 ppm more shielded as compared
to that in the less sterically crowded 1a +. The 1-pyrenyl
moiety is quite effective in charge delocalization; the
pyrenium ion character of these benzylic carbocations is
clearly revealed on the basis of ∆δ13C values and the
nonequivalence of the methyls, indicative of significant
double-bond character in the Py-C+ bond for 1a +.
For 2a +, charge delocalization into the phenyl groups
is taking place, but π-participation by the 1-pyrenyl unit
Resu lts a n d Discu ssion
Carbinols 1-9 (Figure 1) are cleanly ionized in FSO3H/
SO2ClF to give their corresponding pyrenylmethylcarbe-
nium ions (Figure 2).
The 1H NMR assignments are based on chemical shifts,
multiplicities, coupling constants, and H-H COSY and
H-C HETCOR relationships. This analysis is combined
with recording of spectra at different temperatures and
1
ion concentrations. The H NMR chemical shifts show
considerable variation as a function of temperature. For
1a +, irradiation of the two methyl resonances caused H-2
and H-10 to exhibit NOE effects in the NOED spectra.
According to coupling constant trends H-2 is at lower
frequency than H-10. This assigns the higher frequency
Me resonance to the methyl group pointing toward H-10.
The assignment of H-5, H-6, and H-8 may be inter-
changed as is often the case in this type of system. For
3a +, in the NOED spectrum, irradiation of the methyl
resonance led to NOE effects at the C+H and the H-2
resonance (assuming that the conformation is such that
the methyl group points away from the more sterically
hindered H-10 position). The 13C NMR assignments were
based on chemical shifts, off-resonance decoupling, and
H-C HETCOR correlations. For 4 and 4a +, COLOC
spectra have been recorded to assure the assignments of
C-10a, C-1, C-1′, and C-2′ via couplings to CH(OH) or
F igu r e 2. Regioisomeric tertiary and secondary prenylmeth-
ylcarbenium ions.

5806 J . Org. Chem., Vol. 62, No. 17, 1997
Laali and Hansen
F igu r e 3. 13C chemical shifts and ∆δ13C values (in parentheses). n.o. means not observed.
is much greater. Indeed, the C+ center in the trityl cation
is at 211 ppm,28 ca. 11.7 ppm more downfield than that
for 2a +.
Cation 2a + whose conformational aspects we have
recently studied29 is so stable it can be generated by
protonation with TFAH at room temperature, where the
Py-C+ rotation is fast but the phenyl groups rotate
slowly. Hence the 1-pyrenyl protons are sharp and those
of phenyls are quite broad.
examples of secondary methylcarbenium ions having a
1-pyrenyl substitutent (3a +-6a +). Among these only 4a +
having a phenyl substitutent exhibited a blue color;
others were red. The most deshielded carbocation carbon
resonance is at 182.6 ppm (5a +) and the most shielded
at 169.9 ppm for the phenyl-substituted cation (4a +). For
the secondary carbocations, increased electron demand
leads to enhanced π-participation by the 1-pyrenyl group,
hence increased pyrenium ion character in the ions.
The ortho and peri hydrogens (H-2, H-10) appear at
8.27 and 8.58 in 1a + and at 7.78 and 7.71 ppm in 2a +.
These proton shielding effects in 2a + are probably caused
by transannular shielding by the slowly rotating phenyl
rings.
The charge delocalization mode into the 1-pyrenyl
moiety for cations 3a +-6a + is quite similar, and a distinct
charge alternation pathway can be deduced on the basis
of the magnitude of ∆δ13C values. The C-10a carbon
which is a ring fusion site is always more positive than
the proton-bearing C-2.
Secon d a r y 1-P yr en ylm eth ylca r ben iu m Ion s (F ig-
u r e 3 a n d 4 a n d Ta ble 1). We have provided four
The CH+ chemical shifts varies between 9.30 (for 6a +)
and 9.88 ppm (for 4a +). Enhanced pyrenium ion char-
acter of the secondary 1-pyrenylmethyl cations is also
reflected in their more deshielded protons as compared
(28) Gu¨nther, H. In NMR Spectroscopy, 2nd ed.; Wiley: New York,
1995; p 500.
(29) Hansen, P. E.; Spanget-Larsen, J .; Laali, K. K. J . Org. Chem.,
to be submitted.

Charge Delocalization in Pyrenylmethylcarbenium Ions
J . Org. Chem., Vol. 62, No. 17, 1997 5807
F igu r e 4. 1H chemical shifts and H,H coupling constants (in parentheses).
13
1
Ta ble 1. Th e Color s, δ C, δ H, a n d Tota l Desh ield in gs for
carbocation substituent. The H-2/H-3 three-bond cou-
pling constants have increased and the H-4/H-5 couplings
have decreased compared to those of the carbinols. The
H-6/H-7 and H-7/H-8 couplings have become nonequiva-
lent (in accord with resonance structures derived from
charge delocalization around the perimeter of the pyrene
moiety). The H-2/H-3 vicinal coupling constants are
usually larger than other couplings.
Va r iou s P yr en e-Su bstitu ted Ca r boca tion s
total
δ δ
C(C+) H(CH+)
deshieldinga
13
1
carbocation
color
1a +
2a +
3a +
4a +
5a +
6a +
7a +
8a +
9a +
burgendy-red 209.20
227.2
∼258b
green
dark-red
blue
deep-red
red
blue-green
dark-red
dark-red
199.32
178.68
169.90
182.5
9.43
9.88
9.53
9.34
229.2 (224.8)c
239.7
239.1d
174.6
213.1d
P r im a r y 1-P yr en ylm et h ylca r b en iu m Ion . At-
tempts to generate the primary carbocation under the
same conditions by ionization of 11 were unsuccessful;
instead, very broad and yet deshielded NMR resonances
were observed, indicative of ionization followed by alky-
lation to give dimers and oligomers presumably of the
type PyCH2Py which are then ring protonated. Our
observations are in line with previous reports that the
primary benzyl cation PhCH2+ is not persistent, forming
polybenzyl.30 Hence additional stability gained by re-
226.20
183.09
243.95
258.2
265.3
∼233.6
9.26
For the individual contributions, see Figure 3. b C-2′ and C-10b
contributions are not included. The number in parentheses
includes the contribution from the methyl group. Changes on
aliphatic carbons are not taken into account.
a
c
d
to the values for the tertiary cations. The peri protons
are always more deshielded than those ortho to the

5808 J . Org. Chem., Vol. 62, No. 17, 1997
Laali and Hansen
placing a phenyl group for a 1-pyrenyl substituent is
inadequate for the primary carbocation to become per-
sistent.
Information) shows a reasonable correspondence, with
increasing deviation for carbons with larger ∆δ13C
values.32a
The 1-pyrenylmethylcarbenium ions show the most
extensive charge alternation path and the largest degree
of pyrenium ion character, followed by 4-pyrenyl- and
2-pyrenyl-substituted carbocations. AM1-calculated C-C+
bond lengths for the tertiary [1a + (1.385 Å); 7a + (1.393
Å); 9a + (1.399 Å)] and secondary carbocations [3a + (1.370
Å); 12a + (1.375 Å); 13a + (1.381 Å)] concur with diminish-
ing double-bond character in each sequence.
Ca r boca tion Sta bility a n d Ca r cin ogen ic Activity.
Ben zo[a ]p yr en e a n d Ben zo[e]p yr en e. As highlighted
in the Introduction, bay-region diol-epoxides are recog-
nized as the ultimate carcinogens which bind covalently
to DNA bases. There is compelling evidence that the
PAH-epoxide ring opening process has carbocationic
character. Bay-region diol-epoxides having steric crowd-
ing in the proximity of the epoxide are usually more
carcinogenic.10 The K-region and non-K-region epoxides
react differently.7
Ter tia r y a n d Secon d a r y 4-P yr en ylm eth ylca r be-
n iu m Ion s (F igu r es 3 a n d 4 a n d Ta ble 1). One
example for each type (7a + and 8a +) has been provided.
Ionization of the 4-carbinols 7 and 8 in the usual manner
gave the corresponding carbocations as dark-red solu-
tions. The 4-pyrenyl-substituted cations exhibit dimin-
ished π-participation by the 4-pyrenyl group and de-
creased stability. Thus the carbocation centers in 7a +
and 8a + are 17 and 13.2 ppm more deshielded, respec-
tively, as compared to the regioisomeric 1a + and 4a +.
The magnitude of the ∆δ13C values suggests a shorter
conjugation path within the 4-pyrenyl unit with C-3a,
C-5, C-6, and C-8 being most deshielded. The hydrogen-
bearing C-5 rather than the ring fusion site (C-3a)
sustains the most positive charge. Nevertheless, the
double-bond character of the C4-C+ bond is evident by
1
nonequivalence of the methyl groups in both H and 13C
NMR spectra.
Taking the same line of argument proposed by
Weissler,17 cation 14a + derived from 14 can be simplified
to 15a +, 16a +, and to 17a + (Figure 5). Similarly, 14b+
Ter tia r y 2-P yr en yld im eth ylca r ben iu m Ion (F ig-
u r es 3 a n d 4 a n d Ta ble 1). Carbocation 9a + was
generated as a dark-red solution from its carbinol precur-
sor. The carbocation center at 243.95 ppm represents
the most deshielded, least delocalized, carbocation gener-
ated in this study.31 The magnitude of ∆δ13C values
defines a conjugation path more or less confined to the
ortho and para carbons. The symmetry element in the
molecule does not allow the extent of C2-C+ double-bond
character to be evaluated from the methyl nonequiva-
lence perspective (see later discussion on AM1 work).
Cation 9a + showed tendency for ring protonation at
higher temperatures.
P r im a r y 2-p yr en ylm eth ylca r ben iu m Ion . Not sur-
prisingly, attempted generation of 2-PyCH2+ from 11 was
unsuccessful; a mixture of the oxonium ion and ring-
protonated 11 were observed instead.
AM1 En ger gies a n d Ca r bon Ch a r ges in P yr en e-
Su bstitu ted Meth ylca r ben iu m Ion s. As a guiding
tool and for comparison with our solution NMR studies,
AM1 energies and charges were calculated for tertiary
carbocations 1a +, 7a +, and 9a +, as well as for the
secondary carbocations 3a +, 12a +, and 13a +.
In accord with NMR-based stability trends, AM1
predicts the relative stability order 3a + (∆Hf° ) 237.60
kcal/mol) > 12a + (∆Hf° ) 243.64 kcal/mol) > 13a + (∆Hf°
) 245.54 kcal/mol) for the regioisomeric secondary pyre-
nyl(methyl)methylcarbenium ions.
Peri interactions in 7a + raise its energy; hence for the
regioisomeric tertiary pyrenyldimethylcarbenium ions,
the relative stability order: 1a + (∆Hf° ) 232.14 kcal/mol)
> 9a + (∆Hf° ) 234.74 kcal/mol) > 7a + (∆Hf° ) 237.08
kcal/mol) was established.
can be simplified to 16b+ as a model. Cations 18c+
f
20c+ serve as models for epoxide ring opening of ben-
zo[e]pyrene bay-region diol-epoxide 18. These “model”
carbocations are analogous to those generated in the
present study.
Comparison of the AM1-calculated changes in carbon
charges for cation 16a + (∆Hf° ) 226.51 kcal/mol) and 1a +
(a specific example of the 14a + cation type) show very
similar patterns: Charge delocalization into the 1-pyre-
nyl moiety is quite extensive and there is significant
pyrenium ion character. On the contrary, the delocal-
ization pattern for 20c+ (∆Hf° ) 232.43 kcal/mol) is more
limited and pyrenium ion character has diminished.
As our model studies did not take into account the role
of the OH group â to the carbocation, we calculated (AM1)
15a + and 19c+ with the OH group equatorial and axial.
The pseudoequatorial OH is the conformation needed for
hydride shift leading to phenol.7 AM1 predicts that the
â-hydroxy carbocation with an axial OH is slightly less
favored over one with an equatorial OH (by 2.56 kcal/
mol). For 19c+ the preference for equatorial OH is even
less (1.2 kcal/mol). In both cases the pattern of AM1
carbon charges remain unchanged.
CNDO/2 calculations by Yeh et al.32b revealed that for
the diol-epoxide of benzo[a]pyrene in the syn-diaxial
conformation, 14a , the 7-OH group influences the charge
at C-9 and C-10 in such a manner that C-9 becomes the
more positive. This influence is probably caused by
hydrogen bonding. This feature is not reflected in the
way the compound reacts in water. As CNDO/2 as well
as AM1 calculations of this study are made in vacuo, the
inclusion of OH groups at C-7 and C-8 is best avoided in
the calculations.
A plot of ∆δ13C- versus AM1-calculated changes in
carbon charges (∆qC(ion) - ∆qC(neutral)) (Supporting
The geometry of the diol-epoxides is likewise influ-
enced by the OH groups at C-7 and C-8. Lehr et al.33
concluded that a maximum overlap between the C-O
bond of the epoxide and the π-orbitals of the aromatic
system is preferable. A geometry with maximum overlap
between the π-system of pyrene and the vacant F-orbital
of the carbocation is obtained in our model compounds.
(30) Olah, G. A.; Prakash, G. K. S.; Sommer, J . Superacids; Wiley:
New York, 1985; p 105.
(31) The 13C chemical shift for the carbocation center in PhC+Me2
is at 255 ppm (see, for example: Heagy, M. D.; Olah, G. A.; Prakash,
G. K. S.; Lomas, J . S. J . Org. Chem. 1995, 60, 7355).
(32) (a) The utility and limitations of AM1 (and other semiempirical
methods) in dealing with charge have been examined for delocalized
carbanions (Tolbert, L. M.; Ogle, M. E. J . Am. Chem. Soc. 1990, 112,
9519) and in several classes of PAH-arenium ions (see ref 24 and Laali,
K. K.; Hollenstein, S.; Harvey, R. G.; Hansen, P. E. J . Org. Chem. 1997,
62, 4023). Whereas quantitative comparisons are unwise, qualitative
use of such relationships is acceptable. (b) Yeh, C. Y.; Fu, P. P.; Belandl,
F. A.; Harvey, R. G. Bio. Org. Chem. 1978, 497.
(33) Lehr, R. E.; Kumar,S.; Levin, W.; Wood, A. W.; Chang, R.;
Conney, A. H.; Yagi, H.; Sayer, J . M.; J erina, D. M. ACS Symp. Ser.
1985, 283, 63

Charge Delocalization in Pyrenylmethylcarbenium Ions
J . Org. Chem., Vol. 62, No. 17, 1997 5809
F igu r e 5. Analogy between “simplified” carbocations generated in this study and those formed by diol-epoxide ring opening.
Ab initio calculations of the MF-FSGO type on car-
bocation 14a + were carried out sometime ago by Ship-
man.34 Inspection of the ab initio π-charges for the triol
carbenium ion clearly defines a charge alternation path
similar to the models reported in the present study.
It is evident from the present study that the charge
delocalization at positions away from the C+ center is
limited and chances of nucleophilic attack at the pyrene
ring are small.
In summary, it appears that the carcinogenic activity
in benzo[a]pyrene resulting from regiospecific binding to
the 2-amino group of guanine via C-10, rather than, for
example, C-7,34b may be traced to enhanced stability and
the higly delocalized nature of 14a + as compared to 14b+
(Figure 5). It can be further proposed that lack of
carcinogenicity in benzo[e]pyrene could stem from lower
relative stability of 18c+.
Our work has provided experimental evidence in
support of “bay-region theory” under stable ion condi-
tions.
Exp er im en ta l Section
Syn th esis of Ca r bin ols. Tertiary carbinols 1, 2, 7, and 9
were synthesized by reacting MeMgBr or PhMgBr with the
corresponding acetyl- or benzoylpyrene, respectively.35
Secondary carbinols 3, 6, and 8 were prepared by LiAlH4
reduction of the corresponding acetyl- and benzoylpyrenes.19
Secondary carbinols 5 (lauryl) and 6 (benzyl) were prepared
in a similar fashion.
1-Acetyl- and 1-benzoylpyrene were prepared by standard
Friedel-Crafts acylation and benzoylation of pyrene.36 2-Acetyl-
and 4-acetylpyrene were synthesized by acetylation of hexahy-
(34) (a) Shipman, L. L. In Polynuclear Aromatic Hydrocarbons;
J ones, P. W., Leber, P., Eds.; Ann Arbor, MI, 1979; pp 569-580. (b)
Zegar, I. S.; Kim, S. J .; J ohansen, T. N.; Horton, P. J .; Harris, C. M.;
Harris, T. M.; Stone, M. P. Biochemistry 1996, 35, 6212.
(36) Vollmann, H.; Becker, H.; Corell, M.; Streek, H. Liebigs Ann.
Chem. 1937, 531, 1.
(35) Lund, H.; Berg, A. Kgl. Dan. Vidensk. Selsk. 1941, 18, 1.

5810 J . Org. Chem., Vol. 62, No. 17, 1997
Laali and Hansen
dropyrene and tetrahydropyrene, respectively, followed by
aromatization with DDQ.37
8.05 (s, 2H) H-4, H-10; 8.05 (d, 2H) H-5, H-9; ∼7.99 (m, 1H)
H-7; 5.12 (d, J ) 5.55 Hz) CH2; 1.94 (t, J ) 5.66 Hz) OH.
12: δ 8.30 (d, J ) 7.90 Hz, 1H) H-3; 8.20 (s, 1H) H-5; 8.13
(m, 3H) H-1, H-6, H-8; 8.04 (s, 2H) H-9, H-10; 7.97 (t, 1H) H-7;
7.97 (t,1H) H-2; 5.74 (q, J ) 6.44 Hz) 2.15 (s (broad), 1H) OH;
1.78 (d, J ) 6.30 Hz, 3H) CH3.
The primary alcohols 10 and 11 were synthesized by LiAlH4
reduction of the corresponding formylpyrenes.19
Ch a r a cter iza tion of th e Ca r bin ols. 1H NMR (CDCl3).
1: δ 9.11 (d, J ) 9.45 Hz, 1H) H-10; 8.15 (m, 2H) H-6, H-8;
8.07 (s, 1H) H-2; 8.06 (s, 1H) H-3; 8.06 (d, J ) 9.45, 1H) H-9;
7.99 (s, 2H) H-4, H-5; 7.99 (t, J ) 7.38, 1H) H-7 and 1.97 (s,
6H) CH3.
13C NMR CDCl3 (data for 1-9 are incorporated into Figure
3). 11: δ 138.56 C-2; 131.39, C-3a, C-10a; 131.09, C-5a, C-8a;
127.75, C-4, C-10; 127.30, C-5, C-9; 125.89, C-7; 125.10, C-6,
C-8; 123.10, C-1, C-3.
2: NMR data reported elsewhere (ref 29).
3: δ 8.17 (d, J ) 9.35 Hz, 1H) H-10; 8.10 (d, 1H) H-6; 8.10
(d, 1H) H-2 or H-3; 8.08 (d, 1H) H-8; 8.05 (d, 1H) H-3 or H-2;
7.98 (d, 1H) H-9; 7.94 (s, 2H) H-4, H-5; 7.93 (t, J ) 7.42 Hz,
1H) H-7; 5.82 (q, J ) 6.45 Hz, 1H); 2.62 (s (broad), 1H) OH;
1.68 (d, J ) 6.61 Hz, 6H) CH3.
4: δ 8.26 (d, J ) 9.31 Hz, 1H) H-10; 8.15 (d, J ) 7.28 Hz,
1H) H-6; 8.15 (d, J ) 7.38 Hz, 1H) H-8; 8.14 (s, 2H) H-2, H-3;
8.02 (s, 2H) H-4, H-5; 8.00 (d, 1H) H-9; 7.96 (t, J ) 7.50 Hz,
1H) H-7; 7.41 (dd, 1H) H-2′; 7.25 (m, 2H) H-3′ and H-4′; 6.81
(d (broad) J ) 3.37 Hz, 1H) CH and 2.54 (d, J ) 3.73 Hz, 1H)
OH.
5: δ 8.28 (d, J ) 9.4 Hz, 1H) H-10; ∼8.16 (m, 2H) H-6, H-8;
8.15 (2H) H-2, H-3; 8.05 (d, J ) 9.4 Hz, 1H) H-9; 8.02 (s) H-4,
H-5; 7.99 (t, J ) 7.7 Hz, 1H) H-7; 5.70 (t, 1H) H-1′; 2.22 (S,
1H) OH; 1.99 (p, CH) H-2′; ∼1.24 (CH2); 0.89 (s) CH3.
6: δ 8.35 (d, J ) 9.35 Hz, 1H) H-10; ∼8.20 (m, 4H) H-2,
H-3, H-6, H-8; 8.10 (d, J ) 9.32 Hz, 1H) H-9; 8.05 (s, 2H) H-4,
H-5; 8.00 (t, 1H) H-7; 7.28 (m, 3H) H-2′, H-3′, and H-4′; 5.98
(dt, 1H) CH; 3.34 (dd, J ) 13.80 Hz, 1H) CH2; 3.22 (dd, J )
13.80 Hz, 1) CH2; 2.28 (d, J ) 2.84 Hz, 1H) OH.
7: δ 8.94 (d, J ) 7.92 Hz, 1H) H-3; 7.92 (d, 1H) H-1; ∼7.92
(m, 2H) H-6, H-8; 7.91 (s, 1H) H-5; 7.84 (d,1H) H-9*, 7.81 (t,
1H) H-7; 7.83 (d, 1H) H-10*; 7.77 (t, 1H) H-2; 1.79 (s, 3H) CH3.
8: δ 8.29 (s, 1H) H-5; 8.23 (d (broad) J ) ∼8 Hz, 1H) H-3;
8.19 (d, 1H) H-6; 8.18 (d, 1H) H-8; 8.12 (d (broad), 1H) H-1;
8.04 (s, 2H) H-9, H-10; 7.99 (t, J ) 7.62 Hz, 1H) H-7; 7.88 (t,
J ) 7.33 Hz, 1H) H-2; 7.51 (dd, 2) H-2′; 7.29 (m, 2H) H-3′,
H-4′; 6.67 (s, 1H) CH, 2.52 (s, 1H) OH.
FSO3H (triple-distilled) and SO2ClF (high-purity grade; in
sealed ampules) were purchased from Aldrich and used
without further purification.
Sta ble Ion Stu d ies. To a cold slurry of the carbinol (ca.
80 mg) in SO2ClF (ca. 0.5 mL) charged into a 10 mm NMR
tube under argon was added a clear homogeneous solution of
FSO3H (1 mL) diluted in SO2ClF (1 mL) at dry ice/acetone
temperature with efficient vortex mixing. O-Protonation/
ionization occurred rapidly forming colored solutions on con-
tact. In some cases the resulting ion solutions were too viscous
for NMR studies and had to be diluted further by addition of
more SO2ClF (ca. 0.5 mL). The resulting cold stock solutions
were transferred by pouring directly from cold 10-5 mm NMR
tubes which had been fully immersed into a dry ice/acetone
bath and flushed with argon. A few drops of precooled CD2Cl2
added to the superacid solution (vortex mixing) served as lock
and reference. The NMR spectra were recorded on a Bruker
250-AC instrument either at 250 MHz for 1H or 62.889 MHz
for 13C spectra. COSY and HETCOR spectra were recorded
as described earlier.26 COLOC spectra were recorded with D2
) 2 × D3 ) 82.5 ms. A total of 300 transients were used in
each of the 32 increments with 2 Hz lines broadening in f2
and sine-bell apodization.
AM1 calculations were carried out using the Hyperchem
package (Hypercube Inc, 1994) which is based on Dewar’s
model.
Ack n ow led gm en t. Partial support at KSU was
provided by the NCI of NIH through an R15 grant
(CA63595-01A1). A NATO collaborative resarch grant
(CRG930113) facilitated this cooperation.
9: δ 8.31 (s, 2H) H-1,H-3; 8.14 (d, J ) 7.75 Hz, 2H) H-6,
H-8; 8.02 (s, 4H) H-4, H-5, H-9, H-10; 7.97 (t, J ) 7.7 Hz, 1H)
H-7; 2.85 (s (broad), 1H) OH; 1.76 (s, 3H) CH3.
10: δ 8.30 (d, J ) 9.30 Hz, 1H) H-10; 8.16 (d, J ) 7.8 Hz,
1H) H-6; 8.15 (d, J ) 7.8 Hz, 1H) H-8; 8.09 (d, J ) 9.29 Hz,
1H) H-9; 8.06 (d, J ) 7.84 Hz, 1H) H-3; 8.01 (dd, J ) 9.29 Hz,
2H) H-4,H-5; 7.98 (t, J ) 7.75 Hz, 1H) H-7; 7.98 (d, J ) 7.62
Hz, 1H) H-2; 5.34 (s, 2H) CH2.
Su p p or tin g In for m a tion Ava ila ble: Plot of ∆qC vs ∆δ13C
(1 page). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from ACS; see any current
masthead page for ordering information.
11: δ 8.17 (d, J ) 9.12, 2H) H-6, H-8; 8.15 (s, 2H) H-1, H-5;
(37) Moyle, M.; Ritchie, E. Aust. J . Chem. 1958, 11, 211.
J O9707343