Synthesis and stable-ion studies of regioisomeric acetylnitropyrenes and nitropyrenyl carbinols and GIAO-DFT study of nitro substituent effects on α-pyrenyl carbocations

Article abstract of DOI:10.1002/ejoc.200800849

Several regioisomeric acetylnitropyrenes were synthesized from isomeric acetylpyrenes by mild protic nitration. Nitration of 1-acetylpyrene gave the 3-, 6-, and 8-nitro derivatives (with 8-nitro as the major isomer), from which the corresponding carbinols [NO₂-Py-CH(OH)CH₃; Py = pyrene] were synthesized. Isomeric 4-acetylnitropyrenes and their corresponding carbinols were synthesized by starting from hexahydropyrene through nitration/aromatization/reduction or aromatization/nitration/reduction sequences. The molecular structures of 4-acetyl-3-nitropyrene and 1-(6-nitropyren-1-yl) ethanol were established by X-ray analysis. Tetrahydropyrene was the starting point for the synthesis of isomeric nitro-2-acetylpyrenes. Low-temperature protonation of 1-acetyl-8-nitropyrene, 4-acetyl-3-nitropyrene, and 2-acetyl-6-nitropyrene in FSO₃H/SO ₂ClF or in FSO₃H/SbF₅ (1:1)/SO₂ClF resulted in the formation of onium dications (by C=O and NO₂ protonation). Charge delocalization (pyrenium ion character) in the carboxonium ions is strongly influenced by the position of the carboxonium group, with the 4-acetyl-3-nitropyrene dication being the most delocalized. Superacid protonation of 1-(3-nitropyren-4-yl)ethanol gave a persistent onium dication rather than an α-pyrenyl carbocation. With all other isolated nitropyrenyl carbinol isomers, low-temperature protonation (with FSO₃H/SO ₂ClF) led to polymerization within 5 min standing at dry-ice-acetone temperature. For these cases, nitro substituent effects on the α-pyrenyl carbocations were gauged by DFT and GIAO-DFT studies. An interesting relationship between the computed nitro tilt angles and the GIAO-derived charge delocalization modes was observed. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800849

FULL PAPER
DOI: 10.1002/ejoc.200800849
Synthesis and Stable-Ion Studies of Regioisomeric Acetylnitropyrenes and
Nitropyrenyl Carbinols and GIAO-DFT Study of Nitro Substituent Effects on
α-Pyrenyl Carbocations
[a]
[a]
[b]
[a]
Kenneth K. Laali,* Maria A. Arrica, Takao Okazaki, and Scott D. Bunge
Keywords: Substituent effects / Arenes / Fused-ring systems / Carbocations / Density functional calculations
Several regioisomeric acetylnitropyrenes were synthesized
from isomeric acetylpyrenes by mild protic nitration. Ni-
tration of 1-acetylpyrene gave the 3-, 6-, and 8-nitro deriva-
tives (with 8-nitro as the major isomer), from which the corre-
protonation). Charge delocalization (pyrenium ion character)
in the carboxonium ions is strongly influenced by the position
of the carboxonium group, with the 4-acetyl-3-nitropyrene
dication being the most delocalized. Superacid protonation
of 1-(3-nitropyren-4-yl)ethanol gave a persistent onium di-
cation rather than an α-pyrenyl carbocation. With all other
isolated nitropyrenyl carbinol isomers, low-temperature pro-
2 3
sponding carbinols [NO -Py-CH(OH)CH ; Py = pyrene] were
synthesized. Isomeric 4-acetylnitropyrenes and their corre-
sponding carbinols were synthesized by starting from hexa-
hydropyrene through nitration/aromatization/reduction or
aromatization/nitration/reduction sequences. The molecular
structures of 4-acetyl-3-nitropyrene and 1-(6-nitropyren-1-yl)
ethanol were established by X-ray analysis. Tetrahydropyr-
ene was the starting point for the synthesis of isomeric nitro-
3 2
tonation (with FSO H/SO ClF) led to polymerization within
5 min standing at dry-ice–acetone temperature. For these
cases, nitro substituent effects on the α-pyrenyl carbocations
were gauged by DFT and GIAO-DFT studies. An interesting
relationship between the computed nitro tilt angles and the
GIAO-derived charge delocalization modes was observed.
2
-acetylpyrenes. Low-temperature protonation of 1-acetyl-8-
nitropyrene, 4-acetyl-3-nitropyrene, and 2-acetyl-6-nitro-
pyrene in FSO H/SO ClF or in FSO H/SbF (1:1)/SO ClF re- (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
3
2
3
5
2
sulted in the formation of onium dications (by C=O and NO
2
Germany, 2008)
Introduction
nificantly more active. The hydroxylated and acetoxylated
derivatives of nitroBaP and nitrobenzo[e]pyrene (nitroBeP)
[
9]
have received limited attention.
Due to their mutagenic and carcinogenic activity and
widespread presence in the environment, nitro derivatives
of polycyclic aromatic hydrocarbons (nitroPAHs) have been
[
1–5]
the subject of intense synthesis and metabolism studies.
Among various classes of nitroPAHs that possess muta-
genic and carcinogenic activity, isomeric nitrobenzo[a]-
pyrene (nitroBaP) and dinitroBaP (see structures for the
parent PAHs and numbering systems) have been more ex-
tensively examined.[ It has been shown that nitro re-
duction and diol epoxide (DE) formation are both impor-
6]
[1,7]
tant in the metabolism of 1-nitro- and 3-nitroBaP.
It was
also demonstrated that the orientation of the nitro group is
a determining factor in the observed mutagenicity.
Whereas nitroPAHs possessing buttressed nitro group(s) are
typically inactive or mildly active, planar nitroPAHs are sig-
[
1,8]
Focusing on mononitropyrene (NP) isomers, the mutage-
nicity order 4-NP Ͼ 2-NP Ͼ 1-NP was established, and
nitro reduction and ring oxidation were both found to be
[
10]
important.
The involvement of the diol epoxide (DE) activation path
in the metabolism of nitroBaP and other nitroPAHs focuses
attention on nitro-substituted benzylic carbocations and the
nitro substituent effect on their relative stability/reactivity.
By using protonation as a model reaction for the genera-
[
[
a] Department of Chemistry, Kent State University,
Kent, OH 44242, USA
Fax: +1-330-672-3816
E-mail: klaali@kent.edu
b] Department of Chemistry for Materials, Mie University,
Tsu 514-8507, Japan
[
11]
tion of electrophiles under stable-ion conditions,
in sev-
Supporting information for this article is available on the
WWW under http://www.eurjoc.org/ or from the author.
eral earlier studies we reported on nitro group diproton-
Eur. J. Org. Chem. 2008, 6093–6105
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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K. K. Laali, M. A. Arrica, T. Okazaki, S. D. Bunge
FULL PAPER
ation in sterically crowded nitropyrenes, and the formation lism of 1-nitro and 3-nitro compounds were shown to in-
of dihydroxyiminium–(oxoiminium) pyrenium dications, volve bay-region oxidation, whereas for 6-nitroBaP, the 1,2-
[
1]
and on nitro group cyclization to generate persistent oxaz- epoxide was suggested to be an intermediate.
oline (and 1,2-oxazine) pyrenium ions.[
12,13]
Given the proposed involvement of bay-region oxidation
In other studies from this laboratory, a series of rego- in the metabolism of nitroPAHs, the ultimate goal of the
isomeric α-pyrene-substituted carbinols were synthesized, present investigation was to gauge nitro substituent effects
from which the corresponding isomeric α-pyrenyl carbo- on the regioisomeric α-pyrenyl carbocations directly by
cations were generated as models for the bay-region carbo- NMR spectroscopy (see Figure 1).
cations formed by the diol epoxide (or epoxide) of BaP and
As highlighted in Schemes 1 and 2, our model study con-
[
11,14,15]
BeP.
This study established the relative stability or- sidered carbocations 1 and 2 to represent simplified models
der shown in Figure 1.
for the 9,10-epoxide (bay region) and the 7,8-epoxide of iso-
meric nitroBaPs, respectively. The charge delocalization
mode in carbocation 1, as derived from earlier work,[
is highlighted in the schemes as dark circles. There is signifi-
cant p–π overlap in carbocation 1, and positive charge is
extensively delocalized throughout the periphery at alter-
nating sites as indicated.
14,15]
By contrast, carbocation 2 exhibits limited p–π overlap
and has a narrow delocalization path (Scheme 2). It is,
therefore, significantly less stable (has higher energy) than
1.
Figure 1. Relative stability order in regioisomeric α-pyrenyl carbo-
cations.
In a separate study,[16] persistent carboxonium–pyrenium
dications were generated in FSO H/SbF (4:1)/SO ClF from
3
5
2
regioisomeric monoacetyl and monobenzoyl-substituted
pyrenes, whereas with diacetyl- and dibenzoylpyrenes dicar-
boxonium ions were formed. It was found that the car-
boxonium group could strongly modulate charge delocal-
ization into the pyrene moiety as a function of substitution
position, and it proved to be a robust electron-withdrawing
substituent, whose electronic response is sensitive to steric
[
16]
factors.
Earlier synthetic and metabolic studies demonstrated
that the metabolism of nitroPAHs is rather complex, and
depending on their structures, one or more of the following
pathways could contribute: ring oxidation, ring oxidation/
nitro reduction, nitro reduction, nitro reduction/esterifica-
Scheme 2. Nitro substituent effects on model carbocation 2 derived
from isomeric nitro carbinols, with carboxonium ions 2a acting as
[
1,7]
tion.
Focusing on the isomeric nitroBaP, the metabo- surrogate for 2 (dark circles signify charge delocalization mode).
Scheme 1. Nitro substituent effects on model carbocation 1 derived from isomeric nitro carbinols, with carboxonium ions 1a acting as
surrogate for 1 (dark circles signify charge delocalization mode).
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Stable-Ion and DFT Studies of Acetylnitropyrenes and Nitropyrenyl Carbinols
The regioisomeric carboxonium ions 1a and 2a (derived effects, as depicted in Scheme 3. Considering the previously
from isomeric nitroacetylpyrenes) are considered as surro- established charge delocalization mode in carbocation type
[
14]
gates for 1 and 2. On the basis of these models, for carbo- 3, nitro substitution at C-6/C-8 would be expected to de-
cation type 1, nitro substitution at C-6 and C-8 (corre- stabilize the carbocation the most, whereas C-1/C-3 substi-
sponding to 3-nitroBaP and 1-nitroBaP) should have a tution should be comparatively less destabilizing. In this in-
more pronounced carbocation destabilization effect relative stance, carboxonium ion 3a could be considered as surro-
to that of 3-nitro (corresponding to 6-BaP), whereas for gate for 3.
carbocation type 2, nitro substitution at C-1/C-3 (corre-
sponding to 6-nitroBaP) should be more strongly destabiliz- tylnitropyrene isomers and nitropyrenyl carbinols and their
ing. low-temperature protonation outcomes, and DFT and
Similar considerations could be applied to BeP and its GIAO-DFT studies of the isomeric nitropyrenyl carbo-
The present study reports on the synthesis of specific ace-
[
17]
bay-region epoxide
in order to gauge nitro substitution cations are also detailed.
Scheme 3. Nitro substitution effects on model carbocations 3 by isomeric nitro carbinols, with carboxonium ions 3a acting as surrogate
for 3 (dark circles signify charge delocalization mode).
Scheme 4. Synthesis of isomeric nitro derivatives of 1-acetylpyrenes and isomeric nitropyrenyl carbinols.
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K. K. Laali, M. A. Arrica, T. Okazaki, S. D. Bunge
FULL PAPER
Results and Discussion
Synthesis of the Nitro Derivatives of 4-Acetylpyrene and
Their Corresponding Carbinols
Synthesis of Isomeric Nitro Derivatives of 1-Acetylpyrene
and 1-Pyrenylethanol
1
,2,3,6,7,8-Hexahydropyrene 10 was the starting point
for the synthesis of the nitro derivatives of 4-acetylpyrene
Scheme 5). Acetylation of 10 gave the corresponding 4-ace-
(
Mild protic nitration of 1-acetylpyrene (Scheme 4) gave
tyl derivative 11 in quantitative yield. At this stage, two dif-
ferent synthetic routes were considered in order to prepare
the isomeric nitro derivatives. Path A (aromatization fol-
lowed by nitration) gave a mixture of four nitro ketones (12,
an isomeric mixture of C-3/C-6/C-8 mononitro derivatives
1
(
compounds 4, 5, and 6) in a 1.3:1:2.9 ratio (from H NMR
spectroscopy). Separation of the three isomers by column
chromatography proved to be challenging due to their sim-
ilar polarities. Only 8-nitroacetyl derivative 6 was isolated
in reasonable amounts from the crude isomeric mixture. In
an effort to change the relative isomer ratios to enable the
separation of the other isomers, nitration of 1-acetylpyrene
was performed with other reagents. With NaNO3 and
NO BF there were no appreciable changes in the relative
1
2a, 12b, and 12c; by using either nitric acid or NaNO ; see
3
Table 1). Of these four ketones, 4-acetyl-3-nitropyrene 12
was obtained in 34% yield, whereas all other fractions ob-
tained by chromatography proved to be mixtures of two
regioisomers.
2
4
proportions of the three nitro isomers, and with Cu(NO3)2
much of the starting material was recovered at the end of
the reaction.
The corresponding carbinols (compound 7, 8, and 9)
were synthesized by reduction of the isomeric mixture of
the nitro ketones by using NaBH . Subsequent column
4
chromatographic separation led to isolation of 7 (20%) and
8
(18%). Finally, carbinol 9 was directly synthesized by re- Table 1. Nitro isomer distribution (by NMR spectroscopy) by using
duction of isolated 6 (62%). The molecular structure of 8 different nitration conditions.
was determined by X-ray analysis (Figure 2 and Supporting
Information). The C–N bond length is 1.461Å, and the N–
O bond lengths are 1.224 and 1.206 Å. The nitro group is
only slightly tilted out of the aromatic plane (≈14°).
[
a] Specified isomers may be interchanged in this group. [b] Speci-
fied isomers may be interchanged in this group.
The molecular structure of compound 12 was confirmed
by X-ray analysis (Figure 3 and Supporting Information).
The C–N bond length is 1.462 Å, and the N–O bond
lengths are 1.235 and 1.242 Å. Due to increased peri strain,
the nitro group in 12 is tilted out of the plane of the aro-
matic periphery by 40.3°. The acetyl group is also tilted (by
circa 42°).
Figure 2. Thermal ellipsoid plot of nitro carbinol 8 (ellipsoids are
drawn at 30% level).
Scheme 5. Synthesis of isomeric nitro derivatives of 4-acetylpyrenes and isomeric nitropyrenyl carbinols.
096 Eur. J. Org. Chem. 2008, 6093–6105
6
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Stable-Ion and DFT Studies of Acetylnitropyrenes and Nitropyrenyl Carbinols
Although path B (nitration of 11, followed by aromatiza-
tion) could be executed efficiently, it turned out to be less
rewarding, as numerous attempts to separate the isomeric
nitro 4-acetyl derivatives proved unsuccessful. Direct re-
duction of the isomeric mixture, similarly yielded a mixture
of isomeric carbinols that proved impossible to separate.
Synthesis of the Nitro Derivatives of 2-Acetylpyrene and
Their Corresponding Carbinols
4
,5,9,10-Tetrahydropyrene 15 served as the starting point
for the synthesis of the nitro derivatives of 2-acetylpyrene
Scheme 6). Following path A, nitration proceeded ef-
(
Figure 3. Thermal ellipsoid plot of 12 (ellipsoids are drawn at 30% ficiently (Ǟ 17), but subsequent aromatization proved un-
level).
successful by use of DDQ (2,3-dichloro-5,6-dicyano-1,4-
benzoquinone), thus preventing the synthesis of the desired
7
-nitro carbinol. By contrast, 2-acetylpyrene 18 was synthe-
Direct reduction of the isomeric mixture of nitro ketones sized from 16 with DDQ in high yield (path B) and subse-
also containing 12) was then attempted by use of NaBH4. quent nitration by use of HNO gave the 1-nitro and 6-nitro
(
3
After 3 h, NMR spectroscopic analysis of the reaction mix- isomers 19 and 20 in 1:2 ratio, from which 20 could be
ture showed that compound 12 had not been reduced, isolated by chromatography. Reduction of the 19/20 iso-
whereas the other isomers had already been converted into meric mixture furnished the corresponding alcohols (21/22)
alcohols. In a separate run, when isolated 12 was allowed and these were successfully separated by column
to react overnight with an excess amount of NaBH , con- chromatography.
4
version to the corresponding carbinol 14 took place in 82%
yield. Column chromatography on the isomeric mixture of
Collective Outcome of the Synthetic Effort as a Basis for
alcohols led to isolation of 6-nitro carbinol 13 (23%) along
Stable-Ion Study
with 3-nitro carbinol 14 (21%). The corresponding 1-nitro
and 8-nitro carbinols were obtained together as one frac-
tion in 1:0.8 ratio (by NMR spectroscopy).
Focusing on the earlier discussed nitro substituent effects
on relative carbocation stabilities and the model studies
Scheme 6. Synthesis of isomeric nitro derivatives of 2-acetylnitropyrenes and isomeric nitropyrenyl carbinols.
Eur. J. Org. Chem. 2008, 6093–6105
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K. K. Laali, M. A. Arrica, T. Okazaki, S. D. Bunge
FULL PAPER
outlined in Schemes 1–3, the collective outcome of the syn-
thetic effort is sketched in Figure 4, showing (by circles) the
various nitro derivatives of isomeric acetylpyrenes and their
corresponding carbinols that were isolated from different
isomeric mixtures. These compounds constituted the start-
ing points for the stable-ion study discussed below.
Figure 4. Sketch of the collective synthetic output (nitro isomers
that were isolated are circled).
Stable-Ion Study
Low-temperature protonation (at dry-ice–acetone tem-
perature) of 1-acetyl-8-nitropyrene 6, 4-acetyl-3-nitropyrene
1
2, and 2-acetyl-6-nitropyrene 20 (as highlighted in Fig-
Scheme 7. Low-temperature protonation of isomeric acetylnitro-
pyrenes and nitropyrenyl carbinols.
ure 4) with FSO H/SO ClF or FSO H/SbF (1:1)/SO ClF
resulted in the formation of nitro-protonated carboxonium
3
2
3
5
2
2
+
2+
2+
1
ions 6H , 12H2 , and 20H2 (Scheme 7). The H and
2
1
3
perature (up to –20 °C) or by protonation with the stronger
C NMR spectroscopic data for the dications are gathered
superacid [FSO H/SbF (1:1)/SO ClF] gave the same result.
3
5
2
in Schemes S1 and S2, respectively (see Supporting Infor-
mation).
We showed previously that isomeric acetyl- and benzo-
ylpyrenes form carboxonium–pyrenium dications in these
media. The comparison underscores the impact of the –
NO H group as a highly powerful electron-withdrawing
substituent. The conformation of the carboxonium group
was established in each case through NOE difference spec-
tra. Whereas carboxonium ions 6H2 and 20H
+
2+
The –CH(Me)OH2 signal of 14H2
is deshielded by
≈
22 ppm from that of 14. Charge delocalization mode in
+
2+
1
4H22 and 12H2 are rather similar, but the magnitude of
13
2+
[
16]
the ∆δ( C) values are larger in 12H . The isomeric nitro
2
+
carbinols 13, 21, and 22 were similarly treated at low tem-
2
perature with FSO H/SO ClF. However, in these cases, fol-
3
2
lowing rapid initial protonation (formation of clear-colored
solutions), polymerization set in within 5 min (formation of
viscous solid materials in the NMR tubes). In order to
gauge the nitro substituent effect in these systems we fo-
cused our efforts on computational studies.
2
+
2+
exhibit
2
3
1
limited charge delocalization on the basis of ∆δ( C) values,
2
+
+
12H2 shows extensive p–π overlap between CO and the
pyrenyl π system. Interestingly, the ring carbon atom bear-
ing the –NO H group is bypassed to minimize destabiliza-
+
2
tion of the system.
Computational Studies
Focusing on the stable-ion study of the regioisomeric car-
binols, low-temperature reaction (–60 °C) of 14 with
The isomeric nitropyrenyl carbinols and their derived
FSO H/SO ClF gave a deep-blue solution whose NMR carbocations (as sketched in Schemes 1–3) were computed
3
2
spectroscopic data (Schemes S1 and S2, Figure S3; Sup- by DFT method at the B3LYP/6-31G(d) level. Table S3
porting Information) were most compatible with the forma- (Supporting Information) presents the energy data. The
tion of the corresponding onium dication 14H22+ (by OH three isomeric nitro derivatives of carbocation 1 (3-NO , 6-
2
and NO protonation), ruling out an α-pyrenyl carbocation NO , and 8-NO ; see Scheme 1) were computed to have ne-
2
2
2
(see also further discussion on the computational aspects). arly identical energies (∆G carbinol Ǟ carbocation). For
Attempts to bring about dehydration by raising the tem- the two isomeric nitro carbocations derived from 2, the 6-
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Stable-Ion and DFT Studies of Acetylnitropyrenes and Nitropyrenyl Carbinols
–1
nitro isomer is slightly more stable (by 1.4 kcalmol ) than
the 1-nitro isomer. As for the isomeric nitro derivatives of
carbocation 3, structure optimization of the 3-nitro deriva-
+
tive resulted in nitro cyclization to form 14a . Among the
remaining three nitro isomers, the 8-nitro derivative is less
–
1
favored (by circa 3 kcalmol ), with the 1-nitro and 6-nitro
derivatives having rather similar energies.
The NMR spectroscopic data for the carbocations and were derived for various isomers on the basis of the magni-
13
their carbinol precursors were computed by the GIAO- tude of the ∆δ( C) values. The data are sketched in
DFT method at the B3LYP/6-311+G(d,p)//B3LYP/6- Schemes 8–10. Also included in these schemes are the com-
31G(d) level, from which the charge delocalization modes puted nitro tilt angles for various carbinol/carbocation
Scheme 8. Relationship between nitro group tilt angle and the GIAO-derived charge delocalization modes in the isomeric carbocations
13
13
of type 1 [∆δ( C) values relative to carbinols in parenthesis; dark circles are roughly proportional to ∆δ( C): threshold was set to
10 ppm].
Scheme 9. Relationship between nitro group tilt angle and the GIAO-derived charge delocalization modes in the isomeric carbocations
13
13
of type 2 [∆δ( C) values relative to carbinols in parenthesis; dark circles are roughly proportional to ∆δ( C): threshold was set to
10 ppm].
Eur. J. Org. Chem. 2008, 6093–6105
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K. K. Laali, M. A. Arrica, T. Okazaki, S. D. Bunge
FULL PAPER
Scheme 10. Relationship between nitro group tilt angle and the GIAO-derived charge delocalization modes in the isomeric carbocations
13
13
of type 3 [∆δ( C) values relative to carbinols in parenthesis; dark circles are roughly proportional to ∆δ( C): threshold was set to
10 ppm].
pairs. Most remarkable are the changes in the nitro tilt tuted in sites bearing limited positive charge (Scheme 9).
angles upon carbinol Ǟ carbocation transformation.
By focusing on the nitro derivatives of carbocation 1 and
by comparing the GIAO-derived charge maps with changes
in the nitro tilt angles (Scheme 8), it can be seen that when
the nitro group is placed in a position with limited positive
charge localization (3-nitro), minimal changes occurs in the
nitro tilt angle upon ionization. By contrast, nitro substitu-
tion at sites bearing significant positive charge results in a
notable increase in the tilting of the nitro group as a way
to minimize repulsive interactions and to lower the energy
of the system. This process rationalizes the computed sim-
ilar relative energies of the three isomers. The nitro tilting
approach enables all three isomeric carbocations to achieve
regular and extensive charge delocalization throughout the
periphery. The computed chemical shift at the carbocation
centers are in the 191–193 ppm range.
Changes in the nitro tilt angle in the carbocations of type
2
is minimal, as in both isomers the nitro group is substi-
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Stable-Ion and DFT Studies of Acetylnitropyrenes and Nitropyrenyl Carbinols
Type 2 carbocations are minimally delocalized, and the
Returning to stable-ion study of carbinol 14, although
computed chemical shift at the carbocation centers is ca. the experimental NMR spectroscopic data are fully com-
2
21 ppm.
patible with the proposed formation of onium dication
Focusing on carbocations of type 3 (Scheme 10), the peri- 14H22 , they could not definitively exclude the formation
+
+
substituted 1-nitro carbocation cyclized upon structure op- of 14a (formed upon structure optimization starting from
timization (Ǟ 14a ) (see ref.
+
[11–13]
for other, experimentally peri-substituted 1-nitro carbocation). In an effort to resolve
observed, examples of nitro cyclization in pyrenium ions; the issue, GIAO-NMR spectroscopic data were computed
see also further discussion). Changes in the nitro tilt angle for 14H22 and 14a , and the charge delocalization maps
upon ionization in the 6-nitro and 1-nitro isomers are mini- were derived for comparison with the experimental data
mal, whereas in the case of the 8-nitro isomer there is sig- (Scheme S5, Supporting Information). This showed that
+
+
+
nificant nitro tilting. These patterns fit in with the GIAO- limited charge delocalization occurs in 14a , and the overall
derived charge maps, showing that only the 8-nitro group charge delocalization pattern for 14H22 is more compatible
is at a site where positive charge accumulates. The magni- with the formation of an onium dication as suggested ear-
tude of positive charge delocalization in type 3 carbocations lier.
+
is in between those of types 1 and 2 (as was the case with
Finally, it is worth pointing out that the charge delocal-
the unsubstituted regioisomeric carbocations), and the ization maps derived on the basis of GIAO-NMR are in
computed chemical shift for the carbocation center is in the overall agreement with the patterns derived from changes
200–210 ppm range.
in the computed NPA charges (Scheme S6, Supporting In-
In order to bridge the model GIAO-DFT study with the formation).
experimentally observed onium dications, bearing in mind
that in the superacid studies the nitro group will be proton-
ated, structure optimizations were extended to nitro-pro-
tonated α-pyrenyl carbodications.
Summary and Conclusions
A series of isomeric acetylnitropyrenes and their re-
Relative energies for various isomeric dications are in- gioisomeric carbinols were synthesized and in several cases
cluded in Table S3 (Supporting Information). Among the individual isomers were isolated and characterized. These
three isomeric nitro derivatives of dication type 1, the 6- served as precursors to regioisomeric α-pyrenyl carbo-
and 8-nitro isomers are equally favored, whereas the 3-ni- cations or carboxonium ions, considered as simplified mod-
–
1
troisomer is ≈3 kcalmol less stable. Stability difference be- els for epoxide ring opening in isomeric nitroBaP and ni-
tween the two isomeric type 2 dications (1-nitro vs. 6-nitro troBeP.
isomer) is much greater relative to the moncations, favoring
Onium dications were generated from three isomeric ni-
the 6-nitro isomer by 11 kcalmol . For the isomeric dicat- troacetylpyrenes and from one nitro carbinol isomer under
–
1
ions of type 3, the stability order 1-NO Ͼ 3-NO Ͼ 6-NO
stable-ion conditions and their charge delocalization modes
2
2
2
Ͼ 8-NO is computed.
were determined on the basis of magnitude of experimental
2
13
Scheme S4 (Supporting Information) presents a side-by- ∆δ( C) values. All other isomeric nitro carbinols polymer-
side comparison of the computed tilt angles in the isomeric ized on exposure to superacid. The structures, NMR chemi-
dications with the GIAO-derived charge delocalization cal shifts, and charge delocalization modes in these systems
+
modes. For the dications of type 1 and type 3 the –NO H
were gauged by DFT and GIAO-DFT.
2
group remains coplanar with the aromatic periphery and
Nitro tilting was recognized as a mechanism by which α-
the charge maps show that in every case the ring carbon pyrenyl carbocations can avoid charge–charge repulsion
+
atom bearing the –NO H group is bypassed to minimize and thus lower their energies. Relative stability in the nitro
2
charge repulsion. This is achieved through subtle changes in derivatives of regioisomeric α-pyrenyl carbocations are in
the charge delocalization modes, which in most cases create the order type 1 Ͼ type 3 Ͼ type 2, which is the same as
adjacent positive charges on 2–3 ring carbon atoms. The the relative stability order in the parent carbocations (as in
+
ring carbon atom bearing the –NO H group is in fact Figure 1). By contrast, the protonated nitro group remains
2
shielded relative to the nitro carbinol precursors. Only the planar with the aromatic periphery and differences in
+
peri-NO H group is tilted out of the aromatic plane due charge delocalization mode occur, resulting in adjacent pos-
2
to steric compression; in this case no nitro cyclization is itive charge formation in the periphery and shielding of the
+
observed. The computed carbocation centers are in the carbon atom bearing the –NO H group.
2
2
22–224 ppm range in type 1 dications and the 221–
Discovery of nitro tilting in the model carbocations ob-
served in this study may be significant in the biochemistry
242 ppm range in type 3 dications.
+
For the type 2 dications, only the ortho-NO H group is of nitroBaP and nitroBeP compounds, for which metabolic
2
forced out of the aromatic plane and charge delocalization studies underscored the involvement of the diol–epoxide ac-
maps show changes resulting in adjacent positive charge tivation path.
formation in the periphery and shielding of the ring carbon
+
atom bearing the –NO H group. The computed carbo-
2
Experimental
cation centers in type 2 dications are in the 233–244 ppm
range.
General: H, 13C, and 2D NMR spectra of the neutral substrates
1
were recorded at 400 MHz with a Bruker Avance-400 instrument.
Eur. J. Org. Chem. 2008, 6093–6105
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6101

K. K. Laali, M. A. Arrica, T. Okazaki, S. D. Bunge
FULL PAPER
CDCl
3
was used as the solvent and as an internal reference (δ =
combined organic extract was then washed with 10% NaOH and
7.26/77.0 ppm; coupling constants J in Hz). Low-temperature
4
dried (MgSO ). Evaporation of the solvent gave a mixture of iso-
NMR spectroscopic studies were performed at 500 MHz with a
mers, which were separated by column chromatography.
Varian Inova-500 instrument at specified temperatures with
1
-Acetyl-8-nitropyrene (6): Partially recovered from the mixture of
1
CD
2
Cl
2
serving as the internal lock and reference. Partial H NMR
regioisomeric ketones as a bright-yellow solid after column
chromatography on silica gel (EtOAc/hexane, 4:6). Yield: 16 mg
assignments for several acetylnitropyrenes had been reported in the
[
18]
The present study provides complete 1H and
13
literature.
C
1
(
14%). H NMR (400 MHz, CDCl
3
, r.t.): δ = 2.93 (s, 3 H, Me),
NMR assignments for the isomeric acetylpyrenes, their nitro deriv-
atives, and carbinol derivatives (see Scheme S4, Supporting Infor-
mation, and the Experimental Section). Mass spectrometric analy-
ses were performed with a Bruker Esquire-LC ESI ion-trap spec-
trometer system in the positive ion mode. The following instrumen-
tal settings were used: capillary: –4000 V; end-plate offset: –500 V;
8
6
.15 (d, J = 9.2 Hz, 1 H, 4-H), 8.21 (d, J = 8.8 Hz, 2 H, 5-H and
-H), 8.31 (d, J = 8.4 Hz, 1 H, 3-H), 8.46 (d, J = 8.0 Hz, 1 H, 2-
H), 8.66 (d, J = 8.4 Hz, 1 H, 7-H), 8.91 (d, J = 10 Hz, 1 H, 10-H),
13
9
.14 (d, J = 10 Hz, 1 H, 9-H) ppm. C NMR (100 MHz, CDCl
r.t.): δ = 30.6 (CH ), 123.0 (CH), 123.7 (CH), 123.9 (c), 124.1 (c),
24.6 (C), 125.4 (CH), 126.7 (CH), 127.7 (CH), 128.2 (C), 128.9 (2
3
,
3
1
–1
nebulizer (N
50 °C; primary skimmer: 22.5 V; secondary skimmer: 4.0 V. The
PAHs were analyzed as silver complexes by using AgOTf in
2 2
): 7.0 psi; dry gas (N ): 7.00 Lmin ; dry temp:
CH), 130.4 (CH), 133.5 (C), 133.9 (C), 134.9 (C), 201.8 (CO) ppm.
IR: ν˜ = 1675, 1585, 1505, 1334, 1313, 1235, 1182, 864, 827 cm .
MS (ES): m/z = 685.1 [2M + Ag] , 396.1 [M + Ag] , 350.0 [(M –
2
–1
+
+
[
19]
107
MeOH. Molecular ion peaks for complexes with the Ag iso-
tope were used for the determination. IR spectra were recorded
+
NO
-Acetyl-6-nitropyrene (20): Obtained as a bright-yellow solid after
column chromatography on silica gel (CH Cl ). Yield: 55 mg
, r.t.): δ = 2.93 (s, 3 H, Me),
.13 (d, J = 9.2 Hz, 1 H, 5-H), 8.19 (d, J = 8.4 Hz, 1 H, 6-H), 8.29
d, J = 8.8 Hz, 1 H, 4-H), 8.35 (d, J = 9.6 Hz, 1 H, 10-H), 8.69 (d,
J = 8.4 Hz, 1 H, 7-H), 8.82 (d, J = 1.2 Hz, 1 H, 1-H), 8.84 (d, J =
2
) + Ag] .
2
with a Bruker Vector 33 IR spectrometer as KBr pellets. CH
and toluene were distilled from CaH under an argon atmosphere
prior the use. FSO H was freshly distilled twice in an all-glass appa-
2 2
Cl
2
2
2
1
(
47%). H NMR (400 MHz, CDCl
3
3
8
(
ratus under an atmosphere of dry nitrogen. SO
from previous studies in our laboratory.
2
ClF was available
1
3
General X-ray Crystal Structure Information: X-ray crystallography
was performed by mounting a crystal onto a thin glass fiber from
a pool of Fluorolube and immediately placing it under a liquid
1.6 Hz, 1 H, 3-H), 8.89 (d, J = 9.6 Hz, 1 H, 9-H) ppm. C NMR
(100 MHz, CDCl , r.t.): δ = 27.1 (CH ), 122.7 (CH), 123.7 (CH),
124.6 (C), 124.8 (CH), 125.3 (C), 125.9 (C), 126.5 (CH), 126.8
(CH), 127.8 (CH), 130.1 (C), 130.9 (C), 131.2 (CH), 131.9 (CH),
135.2 (C), 135.6 (C), 143.3 (C), 198.0 (CO) ppm. IR: ν˜ = 1686,
1630, 1557, 1505, 1334, 1309, 1212, 891, 841, 813, 706 cm . MS
(ES): m/z = 687.1 [2M + Ag] , 398.0 [M + Ag] , 242.9 [M –
NO ] .
3
3
N
2
cooled N
tion used was graphite monochromatized Mo-K
.7107 Å). The lattice parameters were optimized from a least-
2
stream with a Bruker AXS diffractometer. The radia-
α
radiation (λ =
–
1
0
+
+
squares calculation on carefully centered reflections. Lattice deter-
mination, data collection, structure refinement, scaling, and data
reduction were carried out by using the APEX2 (version 1.0–27)
software package. Data collection parameters are given in Table S1
+
2
4-Acetyl-3-nitropyrene (12): Obtained as a red solid by nitration of
4-acetylpyrene after column chromatography on silica gel
(Supporting Information). Each structure was solved by direct
1
(CH
2
Cl
2
). Yield: 40 mg (34%). H NMR (400 MHz, CDCl
3
, r.t.):
methods. This procedure yielded a number of the C, N, and O
atoms. Subsequent Fourier synthesis yielded the remaining atom
positions. The hydrogen atoms were fixed in positions of ideal ge-
ometry and refined within the XSHELL software. These idealized
hydrogen atoms had their isotropic temperature factors fixed at 1.2
or 1.5 times the equivalent isotropic U of the C atoms to which
they were bonded. The final refinement of each compound in-
cluded anisotropic thermal parameters on all non-hydrogen atoms.
Compound 8 contained two structurally similar, but crystallo-
graphically nonequivalent, molecules per unit cell. Only one of the
molecules is shown in Figure 2. In addition, the second molecule
in 8 has an O atom that was found to be disordered over two posi-
tions (O4 and O4A). This disorder was modeled and the appropri-
ate final formula was included in the final refinement. For ad-
ditional information concerning data collection and final structural
solutions of compounds 12 and 8 see the Supporting Information.
δ = 2.93 (s, 3 H, Me), 8.15 (d, J = 8.8 Hz, 1 H, 10-H), 8.17 (t, J =
8.0 Hz, 1 H, 7-H), 8.23 (d, J = 9.2 Hz, 1 H, 9-H), 8.26 (d, J =
8
.0 Hz, 1 H, 1-H), 8.40 (dd, J = 7.6 and 2.8 Hz, 2 H, 6-H and 8-
1
3
H), 8.52 (d, J = 8.8 Hz, 1 H, 2-H), 8.57 (s, 1 H, 5-H) ppm.
C
NMR (100 MHz, CDCl
CH), 124.3 (C), 125.5 (CH), 125.9 (C), 127.3 (CH), 127.6 (CH),
28.4 (CH), 128.8 (C), 129.3 (CH), 130.1 (CH), 130.9 (C), 131.2
CH), 134.7 (C), 135.5 (C), 144.8 (C), 200.1 (CO) ppm. IR: ν˜ =
3 3
, r.t.): δ = 28.5 (CH ), 120.0 (C), 122.7
(
1
(
1
=
–
1
714, 1589, 1506, 1339, 1222, 1184, 1158, 856 cm . MS (ES): m/z
+
+
+
2
687.1 [2M + Ag] , 396.0 [M + Ag] , 243.0 [M – NO ] . For the
X-ray data, see the Supporting Information.
2
1
-Acetyl-7-nitro-4,5,9,10-tetrahydropyrene (17): To the solution of
6 (125 mg, 0.5 mmol) in acetic acid (20 mL; kept at 0 °C) was
3
added a solution of NaNO (42 mg, 0.5 mmol) in trifluoroacetic
acid (10 mL). Acetic anhydride was then added, and the resulting
solution was kept at 0 °C for 30 min and then for 3 h at room tem-
perature. Water was then added, and the organic phase was ex-
CCDC-695963 (for 12) and -695964 (for 8) contain the supplemen-
tary crystallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
tracted with CH
was washed with 10% NaOH and dried with MgSO
of the solvent gave a solid that was purified by column chromatog-
2
Cl
2
(3ϫ10 mL). The combined organic extract
4
. Evaporation
1
raphy (CH
CDCl , r.t.): δ = 2.92–3.00 (m, 8 H), 3.00 (s, 3 H, CH
H, 1-H and 3-H), 7.99 (s, 2 H, 6-H, 8-H) ppm.
2
Cl
2
). Yield: 105 mg (72%). H NMR (400 MHz,
General Procedure for the Synthesis of Acetylnitro Derivatives Start-
ing from the Corresponding Acetylpyrenes: To a solution of the ace-
3
3
), 7.72 (s, 2
tylpyrene derivative (100 mg, 0.4 mmol) in AcOH/CH
2 2
Cl (1:1,
5
mL) at room temperature was added 50% HNO (0.04 mL). The
3
General Procedure for Carbonyl Reduction: Under an argon atmo-
sphere, the isomeric mixture resulting from nitration of a specific
acetylpyrene (or a particular nitro isomer isolated following chro-
matographic separation; typically 0.35 mmol) was dissolved in
reaction mixture was allowed to stir at room temperature, and the
progress of the reaction was monitored by TLC. Once the starting
material was totally consumed (usually 2–3 h), water was added,
and the organic phase was extracted with CH
2
Cl
2
(3ϫ10 mL). The
2 2 4
MeOH/CH Cl (1:1, 4 mL) and NaBH (34 mg, 1 mmol) was
6102
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 6093–6105

Stable-Ion and DFT Studies of Acetylnitropyrenes and Nitropyrenyl Carbinols
added in portions to the previous solution kept at 0 °C. The reac-
tion mixture was allowed to stir at 0 °C for 15 min and then
warmed up to room temperature. After 2–3 h, water was added,
8.4 Hz, 1 H, 1-H), 8.22 (d, J = 8.8 Hz, 1 H, 10-H), 8.24 (d, J =
8.0 Hz, 1 H, 2-H), 8.32 (dd, J = 7.6 and 1.6 Hz, 1 H, 8-H), 8.34
1
3
(dd, J = 7.6 and 1.6 Hz, 1 H, 6-H), 8.66 (s, 1 H, 5-H) ppm.
C
and the organic phase was extracted with CH
combined organic layer was washed with brine and dried (MgSO
The solvent was removed under vacuum to obtain a mixture of
isomeric nitro alcohols, which were then purified by column
chromatography.
2
Cl
2
(3ϫ5 mL). The
).
NMR (100 MHz, CDCl , r.t.): δ = 25.3 (CH ), 66.3 (CH), 121.3
3
3
4
(C), 122.1 (CH), 123.3 (C), 124.5 (CH), 126.1 (C), 127.1 (CH),
127.2 (2CH), 127.4 (CH), 129.1 (CH), 129.7 (CH), 130.3 (C), 130.8
(C), 134.2 (C), 138.6 (C), 145.4 (C) ppm. IR: ν˜ = 3494 (br.), 2969,
–
1
2924, 1585, 1508, 1336, 1103, 880, 846 cm . MS (ES): m/z = 691.2
+
+
+
[
2M + Ag] , 400.1 [M + Ag] , 274.0 [M – OH] .
1
-(3-Nitropyren-1-yl)ethanol (7): Obtained as a yellow solid after
column chromatography on silica gel (EtOAc/CH Cl , 1:9). Yield:
, r.t.): δ = 1.80 (d, J =
), 2.23 (br. s, 1 H, OH), 5.99 (q, J = 6.4 Hz, 1 H,
2
2
1-(6-Nitropyren-4-yl)ethanol (13): Obtained as a bright-yellow solid
1
21 mg (20%). H NMR (400 MHz, CDCl
.4 Hz, 3 H, CH
3
after column chromatography on silica gel (EtOAc/hexane, 4:6).
1
6
3
Yield: 23 mg (23%). H NMR (400 MHz, CDCl
3
, r.t.): δ = 1.84 (d,
CHCH
9
8
3
), 8.13 (t, J = 7.6 Hz, 1 H, 7-H), 8.29 (d, J = 9.6 Hz, 1 H, J = 6.4 Hz, 3 H, Me), 2.30 (br. s, 1 H, OH), 5.88 (q, J = 6.8 Hz, 1
-H), 8.30 (d, J = 9.2 Hz, 1 H, 5-H), 8.32–8.35 (m, 2 H, 6-H and H, CHCH ), 8.06 (d, J = 9.2 Hz, 1 H, 10-H), 8.11 (d, J = 8.4 Hz,
-H), 8.37 (d, J = 9.1 Hz, 1 H, 10-H), 8.83 (d, J = 9.2 Hz, 1 H, 4-
3
1 H, 8-H), 8.13 (t, J = 8.0 Hz, 1 H, 2-H), 8.21 (d, J = 8.8 Hz, 1 H,
13
H), 8.93 (s, 1 H, 2-H) ppm. C NMR (100 MHz, CDCl
5.1 (CH
C), 124.1 (C), 125.5 (C), 127.1 (CH), 127.5 (CH), 127.7 (CH), NMR (100 MHz, CDCl
30.4 (C), 130.5 (C), 130.9 (CH), 131.1 (CH), 139.2 (C), 143.2 (C) (CH), 122.7 (CH), 123.2 (CH), 123.9 (C), 124.1 (CH), 124.3 (C),
ppm. IR: ν˜ = 3407 (br.), 1621, 1118, 964, 807, 668, 603 cm . MS 124.4 (C), 126.7 (CH), 126.8 (CH), 127.7 (CH), 127.9 (C), 131.0
3
, r.t.): δ = 9-H), 8.31 (d, J = 7.6 Hz, 1 H, 1-H), 8.59 (d, J = 7.2 Hz, 1 H, 3-
1
3
2
(
1
3
), 66.9 (CH), 119.4 (CH), 121.6 (CH), 122.1 (CH), 123.9
H), 8.61 (d, J = 8.4 Hz, 1 H, 7-H), 9.05 (s, 1 H, 5-H) ppm.
C
3
, r.t.): δ = 24.6 (CH ), 68.0 (CH), 117.5
3
–
1
+
+
(
+
ES): m/z = 691.2 [2M + Ag] , 398.1 [M + Ag] , 382.0 [(M – OH)
Ag] , 336 [(M – OH – NO
(CH), 131.4 (C), 134.7 (C), 143.1 (C), 144.9 (C) ppm. IR: ν˜ = 3407
+
+
+
–1
2
) + Ag] , 274.0 [M – OH] .
(br.), 1621, 1509, 1117, 795, 688, 602 cm . MS (ES): m/z = 689.1
+
+
+
[
[
2M + Ag] , 400.0 [M + Ag] , 382.0 [(M – OH) + Ag] , 336.0
1-(6-Nitropyren-1-yl)ethanol (8): Obtained as a bright-yellow solid
+
+
2
(M – OH – NO ) + Ag] ,273.0 [M – OH] .
after repeated column chromatography on silica gel on the fraction
that was enriched with this isomer. The percent recovery was 18%
1-(1-Nitropyren-2-yl)ethanol (21): Obtained as a brown-yellow solid
1
(18 mg). H NMR (400 MHz, CDCl
3
, r.t.): δ = 1.76 (d, J = 6.5 Hz, after column chromatography on silica gel (EtOAc/hexane, 6:4).
1
3
H, Me), 2.42 (br. s, 1 H, OH), 5.95 (d, J = 6.5 Hz, 1 H, CHCH
3
),
Yield: 34 mg (33%). H NMR (400 MHz, CDCl
J = 6.4 Hz, 3 H, Me), 2.49 (br. s, 1 H, OH), 5.40 (q, J = 7.2 Hz, 1
H, CHCH ), 7.95 (d, J = 9.2 Hz, 1 H, 3-H), 8.06 (d, J = 8.8 Hz, 1
J = 8.0 Hz, 1 H, 10-H), 8.44 (d, J = 9.2 Hz, 1 H, 2-H), 8.56 (d, J H, 10-H), 8.08 (t, J = 7.6 Hz, 1 H, 7-H), 8.15 (d, J = 8.8 Hz, 1 H,
3
, r.t.): δ = 1.74 (d,
8.01 (d, J = 9.2 Hz, 1 H, 3-H), 8.04 (d, J = 8.4 Hz, 1 H, 8-H), 8.18
(d, J = 9.4 Hz, 1 H, 4-H), 8.26 (d, J = 8.0 Hz, 1 H, 9-H), 8.33 (d,
3
1
3
=
8.4 Hz, 1 H, 7-H), 8.74 (d, J = 9.4 Hz, 1 H, 5-H) ppm. C NMR 10-H), 8.20 (d, J = 9.6 Hz, 1 H, 5-H), 8.23–8.27 (m, 2 H, 6-H and
1
3
(100 MHz, CDCl
3
, r.t.): δ = 25.5 (CH
3
), 67.3 (CH), 121.2 (CH),
8-H), 8.41 (s, 1 H, 1-H) ppm. C NMR (100 MHz, CDCl
3
, r.t.): δ
122.6 (CH), 123.8 (CH), 124.0 (CH), 124.0 (C), 125.1 (C), 125.3
= 25.1 (CH ), 66.3 (CH), 120.3 (CH), 122.1 (CH), 122.6 (C), 123.6
3
(C), 125.7 (CH), 126.8 (CH), 127.1 (C), 127.3 (CH), 129.4 (C), (C), 123.9 (C), 126.6 (CH), 126.9 (CH), 127.0 (CH), 127.0 (CH),
1
1
31.5 (CH), 134.4 (C), 142.1 (C), 142.8 (C) ppm. IR: ν˜ = 3422 (br.),
129.7 (CH), 130.3 (C), 130.7 (CH), 130.8 (C), 132.8 (C), 134.9 (C),
–1
585, 1504, 1294, 1106, 844, 810, 710 cm . MS (ES): m/z = 691.2
143.4 (C) ppm. IR: ν˜ = 3440 (br.), 2924, 1594, 1513, 1261, 1106,
+
+
+
–1
+
[2M + Ag] , 398.0 [M + Ag] , 382.0 [(M – OH) + Ag] , 274 [M –
799, 709 cm . MS (ES): m/z = 691.1 [2M + Ag] , 399.0 [M +
+
+
+
+
OH] . For X-ray data, see the Supporting Information.
-(8-Nitropyren-1-yl)ethanol (9): Obtained by reduction of its corre-
sponding nitro ketone isomer 6 (16 mg) as a yellow solid after col-
umn chromatography on silica gel (EtOAc/CH Cl , 1:9). Yield:
, r.t.): δ = 1.79 (d, J =
.4 Hz, 3 H, Me), 2.15 (br. s, 1 H, OH), 6.03 (q, J = 6.4 Hz, 1 H, H, CHCH
), 8.07 (d, J = 8.8 Hz, 1 H, 5-H), 8.16 (d, J = 8.4 Hz, 1 H,
-H), 8.21 (d, J = 8.8 Hz, 1 H, 4-H), 8.34 (d, J = 8.0 Hz, 1 H, 3-
2
Ag] , 352.0 [(M – NO ) + Ag] , 274.1 [M – OH] .
1
1-(6-Nitropyren-2-yl)ethanol (22): Obtained as a bright-yellow solid
after column chromatography on silica gel (EtOAc/hexane, 6:4).
1
2
2
Yield: 61 mg (60%). H NMR (400 MHz, CDCl
3
, r.t.): δ = 1.72 (d,
1
1
6
0 mg (62%). H NMR (400 MHz, CDCl
3
J = 6.4 Hz, 3 H, Me), 2.45 (br. s, 1 H, OH), 5.37 (q, J = 6.4 Hz, 1
), 7.95 (d, J = 8.8 Hz, 1 H, 9-H), 8.01 (d, J = 8.4 Hz, 1
3
CHCH
6
3
H, 8-H), 8.10 (d, J = 8.8 Hz, 1 H, 10-H), 8.13 (d, J = 9.6 Hz, 1 H,
4-H), 8.20 (d, J = 1.2 Hz, 1 H, 1-H), 8.24 (d, J = 1.2 Hz, 1 H, 3-
H), 8.54 (d, J = 8.4 Hz, 1 H, 7-H), 8.72 (d, J = 9.6 Hz, 1 H, 5-H)
H), 8.38 (d, J = 8.0 Hz, 1 H, 2-H), 8.62 (d, J = 10.0 Hz, 1 H, 10-
H), 8.66 (d, J = 8.4 Hz, 1 H, 7-H), 8.93 (d, J = 9.6 Hz, 1 H, 9-H)
1
3
3 3
ppm. C NMR (100 MHz, CDCl , r.t.): δ = 26.1 (CH ), 70.4 (CH),
ppm. 13C NMR (100 MHz, CDCl
, r.t.): δ = 25.6 (CH
21.9 (CH), 122.7 (CH), 123.9 (CH), 123.9 (C), 124.4 (C), 124.5
CH), 125.4 (C), 126.5 (C), 126.6 (CH), 126.7 (CH), 127.9 (CH), 130.9 (C), 131.3 (CH), 134.8 (C), 142.2 (C), 144.9 (C) ppm. IR: ν˜
), 67.4 (CH), 121.8 (CH), 122.5 (CH), 122.8 (C), 123.9 (CH), 124.1 (CH), 124.2
3
3
1
(
(C), 124.3 (C), 124.4 (CH), 126.9 (CH), 130.0 (C), 130.6 (CH),
1
=
=
30.5 (C), 130.9 (CH), 135.4 (C), 141.9 (C), 143.0 (C) ppm. IR: ν˜
= 3440 (br.), 2967, 1629, 1594, 1562, 1495, 1212, 949, 880, 862,
–1
–1
+
3400 (br.), 2924, 1585, 1501, 1294, 1109, 851 cm . MS (ES): m/z
780, 705 cm . MS (ES): m/z = 691.1 [2M + Ag] , 399.0 [M +
+
+
+
+
+
+
689.2 [2M + Ag] , 399.1 [M + Ag] , 382.0 [(M – OH) + Ag] ,
74 [M – OH] .
Ag] , 382.0 [(M – OH) + Ag] , 274.0 [M – OH] .
+
2
General Procedure for Acetylation: Under an argon atmosphere to
1-(3-Nitropyren-4-yl)ethanol (14): Obtained by reduction of its cor-
a suspension of AlCl
3
(73 mg, 0.55 mmol) in freshly distilled
responding nitro ketone isomer (42 mg) as a brown-yellow solid.
Yield: 35 mg (82%). More of this compound was isolated out of
CH Cl was slowly added acetyl chloride (43 mg, 0.55 mmol) at
2
2
0 °C. The reaction mixture was stirred at room temperature until a
clear solution resulted. The temperature was once again lowered
to 0 °C, and a solution of tetrahydropyrene or hexahydropyrene
(0.5 mmol) dissolved in CH Cl (2 mL) was then introduced into
2 2
the previous solution. The reaction mixture was then allowed to
stir for an additional 2 h at room temperature. HCl (10%) and
the isomeric mixture of the carbinols, following column chromatog-
1
raphy on silica gel (EtOAc/hexane, 4:6). Yield: 9 mg (21%).
NMR (400 MHz, CDCl
.21 (br. s, 1 H, OH), 5.50 (q, J = 6.0 Hz, 1 H, CHCH
J = 8.8 Hz, 1 H, 9-H), 8.13 (t, J = 7.6 Hz, 1 H, 7-H), 8.19 (d, J =
H
3
, r.t.): δ = 1.69 (d, J = 6.0 Hz, 3 H, Me),
), 8.11 (d,
2
3
Eur. J. Org. Chem. 2008, 6093–6105
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6103

K. K. Laali, M. A. Arrica, T. Okazaki, S. D. Bunge
susceptibility for 13C), calculated with molecular symmetry of T
FULL PAPER
water were then added, and the two phases were separated. Follow-
d
ing extraction with CH
tract was washed with brine and dried (MgSO
the solvent gave a yellow solid, which was used without further
purification in the following steps.
2
Cl
2
(3ϫ10 mL), the combined organic ex-
). Evaporation of
at the same level of theory. The ring centers were defined as the
simple average of Cartesian coordinates for all the carbon atoms
in the ring. Planes of the rings were calculated by least-square
methods by using coordinates of the all carbon atoms in the rings.
4
4
1
4
-Acetyl-1,2,3,6,7,8-hexahydropyrene (11): Yellow solid. Yield:
Supporting Information (see also the footnote on the first page of
this article): Specific NMR assignments; X-ray analysis; GIAO
1
22 mg (98%). H NMR (400 MHz, CDCl
H), 2.64 (s, 3 H, CH
3
, r.t.): δ = 1.98–2.11 (m,
), 3.03–3.12 (m, 6 H), 3.28 (t, J = 6.0 Hz, 2 NMR; charge delocalization maps and nitro tilt angles for the di-
3
2+
H), 7.17 (d, J = 7.0 Hz, 1 H), 7.21 (d, J = 7.0 Hz, 1 H), 7.38 (s, 1
H, 5-H) ppm.
cations; GIAO-NMR and charge delocalization maps for 14H
2
+
and 14a ; energy and Cartesian coordinates for the optimized
structures by DFT calculations; charge delocalization maps based
on NPA charges; selected NMR spectra.
2
-Acetyl-4,5,9,10-tetrahydropyrene (16):[20] Yellow solid. Yield:
1
1
16 mg (94%). H NMR (400 MHz, CDCl
3
, r.t.): δ = 2.62 (s, 3 H,
), 7.10 (d, J = 8.0 Hz, 2 H, 6-H and 8-H),
.19 (t, J = 8.0 Hz, 1 H, 7-H), 7.68 (s, 2 H, 1-H and 3-H) ppm.
3 2
CH ), 2.92 (m, 8 H, CH
7
Acknowledgments
General Procedure for Aromatization: To a solution of the corre-
sponding acetyltetrahydropyrene, acetylhexahydropyrene, or their
nitro derivative (typically 0.4 mmol) was added DDQ (1.2 mmol)
in dry toluene (40 mL), and the mixture was heated to reflux for
We thank Prof. T. Yamato (Saga University, Japan) for kindly send-
ing us a sample of tetrahydropyrene. Support of our work in the
PAH area under “Reactive Intermediates of Carcinogenesis of
PAHs” by the National Cancer Institute of the National Institutes
of Health (2R15CA078235-02A1) is gratefully acknowledged.
6
h. After cooling to room temperature, the reaction was stirred
with a saturated sodium sulfite solution and filtered. The organic
layer was separated after extraction with toluene, and the organic
extract was washed with water (twice) and dried (MgSO
4
). Evapo-
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over silica gel.
(
Eds.: S. K. Yang, B. D. Silverman), CRC Press, Boca Raton,
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[
[
2] F. A. Beland, R. H. Heflich, P. C. Howard, P. P. Fu in ACS
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4
-Acetylpyrene (11a):[16] Obtained as a brown solid after column
1
chromatography (CH
400 MHz, CDCl , r.t.): δ = 2.90 (s, 3 H, CH
.22–8.29 (m, 3 H), 8.53 (s, 1 H, 5-H), 9.08 (dd, J = 8.0 and 0.8 Hz,
H, 3-H) ppm.
2
Cl
2
). Yield: 76 mg (78%).
H NMR
15.
(
8
1
3
3
), 8.01–8.12 (m, 4 H),
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[
16]
2
(
-Acetylpyrene (18): Obtained as a brownish solid. Yield: 78 mg
1
80%). H NMR (400 MHz, CDCl
3
, r.t.): δ = 2.88 (s, 3 H, CH
3
),
1106.
8.02–8.23 (m, 7 H), 8.67 (s, 2 H, 1-H and 3-H) ppm.
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0
[
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[
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[24]
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[
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[
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Received: September 3, 2008
Published Online: November 18, 2008
Eur. J. Org. Chem. 2008, 6093–6105
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6105