Synthesis of uniformly 13C-labeled polycyclic aromatic hydrocarbons

Article abstract of DOI:10.1039/c0ob01107j

Convergent synthetic pathways were devised for efficient synthesis of a series of uniformly ¹³C labeled polycyclic aromatic hydrocarbons de novo from U-¹³C-benzene and other simple commercially-available ¹³C-starting compounds. All target products were obtained in excellent yields, including the alternant PAH U-¹³C-naphthalene, U-¹³C-phenanthrene, U-¹³C-anthracene, U- ¹³C-benz[a]anthracene, U-¹³C-pyrene and the nonalternant PAH U-¹³C-fluoranthene.

Full text of DOI:10.1039/c0ob01107j

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PAPER
Synthesis of uniformly 13C-labeled polycyclic aromatic hydrocarbons†
Zhenfa Zhang, Ramiah Sangaiah,‡ Avram Gold* and Louise M. Ball*
Received 2nd December 2010, Accepted 21st April 2011
DOI: 10.1039/c0ob01107j
Convergent synthetic pathways were devised for efficient synthesis of a series of uniformly 13C labeled
polycyclic aromatic hydrocarbons de novo from U-13C-benzene and other simple commercially-available
13C-starting compounds. All target products were obtained in excellent yields, including the alternant
PAH U-13C-naphthalene, U-13C-phenanthrene, U-13C-anthracene, U-13C-benz[a]anthracene,
U-13C-pyrene and the nonalternant PAH U-13C-fluoranthene.
tion mass spectrometric quantification protocols in bioanalytical
or environmental analyses.
Introduction
The biological and spectroscopic properties of polycyclic aromatic
hydrocarbons (PAH) are a focus of attention in physico-chemical,
toxicological, analytical, and environmental studies. PAH labeled
with 13C have been useful in investigations encompassing such di-
Results and discussion
Although there are a large number of classical methods for
verse areas as NMR hyperfine shifts and coupling mechanisms,1a–d
metabolism, biological activity2 and environmental distribution,
such as transport and aging of PAH in sediments.3 PAH have
been identified as mutagenic and carcinogenic pollutants in many
of the National Priorities List sites in the US4 and bioremedi-
ation has gained attention as an approach to degrading PAH
in the environment, especially those PAH with five or fewer
fused rings.5a–e The use of stable isotope probing to identify
microorganisms which deplete PAH in the environment through
metabolic transformation6a–d relies on the availability of PAH
substrates highly enriched in 13C. However, such substrates are
not commonly available but require de novo synthesis from a very
limited pool of 13C labeled starting materials, severely limiting
application of this technique. Currently, naphthalene is the only
PAH available commercially as the U-13C isotopomer.
building PAH ring systems,7 the limited number of commercially
available U-13C starting chemicals severely restricts the freedom
of design of synthetic pathways. The high cost of the labeled
starting compounds also demands that synthetic routes be efficient
with high overall yields. U-13C-Tetralone (1), accessible through
classical Haworth synthesis from commercially available U-13C-
succinic anhydride and U-13C-benzene (Scheme 1), was chosen as
the most versatile intermediate for the preparation of all target
PAH. The route to each target was optimized by synthesis on the
appropriate scale using NA isotopomers. Optimization of yields
is critical to identifying practical routes and thus, while a number
of synthetic routes are based on classical reactions, the reaction
conditions and choice of catalyst established in this study are
specifically geared towards application to PAH and are thus a
significant addition to the arsenal of techniques available.
We report synthesis of the series of alternant U-13C-labeled
PAH: naphthalene, phenanthrene, anthracene, benz[a]anthracene
and pyrene and the nonalternant U-13C-labeled PAH fluoranthene
in high yield from U-13C-benzene. By employing appropriate 13C-
labeled and natural abundance (NA) isotopomers as starting
materials, PAH partially 13C-labeled at specific sites can also be
synthesized using the schemes presented below for use in spec-
troscopic studies or investigations of metabolism or biosynthesis.
Multiply 13C-labeled PAH and derivatives are also valuable as
standards in developing highly sensitive and specific isotope dilu-
Scheme 1
U-13C-anthracene (6)
For the synthesis of anthracene (Scheme 2), tetralone was first
reduced to tetralin (2) for Friedel–Crafts acylation. Among many
procedures for the reduction, Li–NH3 reduction was initially
selected because of the mild reaction conditions and reported high
yield;8 however, our yields were variable and inconsistent. This
observation is in accord with a report of multiple products from
the reduction8a involving partial reduction of the benzene ring,
Department of Environmental Sciences and Engineering, CB7431, The
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
27599, USA
† Electronic supplementary information (ESI) available: Reaction proce-
dures for all intermediates not given in the text; complete 1H and 13C
NMR spectra for all intermediates and target compounds. See DOI:
10.1039/c0ob01107j
‡ Deceased
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Scheme 3
Scheme 2
use with labeled reagents. Instead, ketone 8 was treated with the
lithium enolate of ethyl acetate13a–c at low temperature based on the
modified procedure of Bodine.14 The resulting hydroxyl ester 12
was aromatized to 13, which was reduced to the corresponding
aldehyde then cyclized to pyrene (14) in 4 steps in 58% yield
from 8.
reduction of the carbonyl group and dimerization. In comparison,
Wolff–Kishner reduction gave yields greater than 90% consistently.
Friedel–Crafts acylation of 2 with succinic anhydride and a
second Wolff–Kishner reduction yielded regiospecific substitution
of a 4-carbon unit at C6 of tetralin (3).9 Cyclization of 3 by
treatment with H2SO4, PPA, and/or combination of PCl5, SnCl4
and AlCl3 has been reported10a–d to give a mixture of 4 and its an-
gular isomer 5 which are difficult to separate. However, cyclization
with methanesulfonic acid (MSA)11 gave the desired linear isomer
4 in high yield when reaction time was less than 30 min. The
proportion of angular isomer 5 increases with increasing reaction
time, which is consistent with the reported reversibility of Friedel–
Crafts acylation,12a–c and 4 being the kinetically favored product.
Reduction of 4 followed by aromatization with DDQ gave 6. A
small amount of contaminating phenanthrene was removed by
recrystallization, for a final overall yield of 16% in 9 steps from
U-13C-benzene.
U-13C-naphthalene (7) and U-13C-benz[a]anthracene (17)
To take advantage of convergent synthetic pathways, we developed
a route to the benz[a]anthracene skeleton based on the Friedel–
Crafts acylation of naphthalene with phthalic anhydride, since
phthalic anhydride may be prepared by the oxidation of tetralin,
tetralone or naphthalene. Tetralone (1) from Scheme 1 served as
the starting point for phthalic anhydride (Scheme 4). Tetralone
can be oxidized to phthalic acid (15) in moderate yield either by
KMnO4 or KO2/18-crown-6 ether.16 We selected oxidation by
15
KMnO4 as a more straightforward procedure and were able to
optimize conditions to achieve a yield of 72%.
U-13C-phenanthrene (11) and U-13C-pyrene (14)
Compounds 11 and 14 have been prepared6c,d from U-13C-
naphthalene (7) via the Haworth synthesis. However, Friedel–
Crafts succinoylation of 7 under the reported conditions leads
to a mixture of 2,3-dihydrophenanthren-4(1H)-one (8) and 3,4-
dihydrophenanthren-1(2H)-one in a 1 : 2 ratio. This route is thus
inefficient when pyrene is the desired target, since only the minor
product (8) can be utilized and separation of the ketones is difficult.
Therefore, the alternative pathway described in Scheme 3 was
devised.
Esterification of 3 in methanol followed by aromatization with
Pd–C yielded 10. Cyclization of fully aromatized naphthalene
derivative 10 in MSA afforded 8 along with only ~ 3% of linear
1
ketone 9 based on H NMR analysis. Transformation of 8 to 11
was straightforward, with anthracene side product removed by
crystallization to give 11 in 67% overall yield from 8.
Scheme 4
This convenient route to 8 also facilitated the synthesis of U-13C-
pyrene. In the published route to pyrene from 6,6d the two-carbon
K-region unit was added by a Reformatsky reaction with ethyl
bromoacetate. While the Reformatsky reaction is robust, yields
are usually moderate, particularly when stoichiometric quantities
of reagents are employed; hence this approach is inefficient for
Tetralone was also the starting point for the synthesis of 7
(63%) in one step by treatment with diethylsulfone in dimethy-
lacetamide/t-BuOK (Scheme 4).17 Friedel–Crafts condensation of
phthalic anhydride with 7 provided the mixture of isomers 16.18a,b
The mixture was then reduced by hydrogen iodide and phosphorus
(Scheme 4) to benz[a]anthracene (17) in 70% overall yield.19
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U-13C-fluoranthene (23)
Conclusions
Many of the published7 syntheses of the nonalternant PAH
fluoranthene are based on fluorene or acenaphthylene, which
are not available as U-13C isotopomers. Recently Larock20 and
Meijere21 reported the direct coupling of substituted benzene
and naphthalene to construct the unique 5-membered ring in
nonalternant PAH. Pathways A and B in Scheme 5 apply this
strategy starting with tetralone.
We have developed synthetic schemes to the U-13C alternant
PAH: naphthalene, phenanthrene, anthracene, benz[a]anthracene
and pyrene and the nonalternant PAH fluoranthene in quantities
ranging from mg to >100 mg. By selection of appropriately
labeled and NA starting compounds, the same routes can be
used to synthesize compounds partially labeled with 13C at specific
sites that will be useful in spectroscopic, toxicological, biological
and analytical applications. Key features in the schemes are the
optimization of reaction conditions to provide target compounds
in high yield and the selection or modification of reaction
conditions and catalysts to direct intramolecular cyclizations on
the aromatic periphery to yield either angular or linear systems in
order to avoid inefficient separation of mixtures, with consequent
decrease in overall yield. Synthesis of the catacondensed pyrene
and nonalternant fluoranthene structures represented a particular
challenge. The pathways described here can be used as a basis for
extending synthetic efforts to additional 13C-labeled aromatic ring
systems.
Experimental section
General: All reactions were first carried out with NA starting
materials in order to optimize the reaction conditions. The NMR
spectra of NA intermediates either matched those of authentic
compounds or were consistent with assigned structures (see
electronic supplementary information). Preparation of the target
U-13C-PAH and key intermediates are presented in this section.
All other procedures and characterization data are included as
electronic supplementary information.
All labeled chemicals were purchased from Cambridge Isotope
Laboratories, Inc. NMR spectra were recorded in chloroform-
d unless otherwise noted. Chemical shift assignments for U-13C
compounds are based on 1H and 13C NMR shifts reported for the
NA compounds and resolved splittings.
U-13C-3,4,5,6,7,8-Hexahydroanthracen-1(2H)-one
(4):
3
(575 mg, 2.4 mmol) was added to MSA (15 mL) and the mixture
heated at 90 ◦C for 30 min under a nitrogen atmosphere. The
mixture was then poured into ice water and extracted with
ether (3 ¥ 40 mL). The combined extracts were washed with
dilute aqueous NaHCO3 (20 mL), water (2 ¥ 15 mL) and brine
(15 mL), then dried over anhydrous MgSO4. After filtration, the
solvent was removed to yield a viscous liquid, which solidified
Scheme 5
◦
upon standing (486 mg, 94% yield). Mp 44–46 C. H NMR26
(300 MHz) d 7.71 (bd, J = 153.9 Hz, 1H, H9), 6.91 (bd, J =
155.0 Hz, 1H, H10), 2.84 (bd, J = 128.0 Hz, 2H, C4H2), 2.74
(bd, J = 126.0 Hz, 4H, C5H2, C8H2), 2.58 (bd, J = 130.7 Hz,
2H, C2H2), 2.06 (bd, J = 130.5 Hz, 2H, C3H2), 1.75 (bd, J =
144.3 Hz, 4H, C6H2, C7H2). 13C NMR27 (75 MHz) d 190.0 (dd,
J = 47.9, 40.8 Hz, C1), 143.3–145.4 (m, C4a), 141.9 (dd, J = 95.2,
53.5 Hz, C10a), 136.2 (dd, J = 95.5, 54.8 Hz, C9a), 130.6–126.9
(m, C8a, C9, C10), 40.3–39.0 (m, C2H2), 30.8–28.8 (m, C4H2,
C5H2, C8H2), 24.5–22.6 (m, C3H2, C6H2, C7H2).
1
In pathway A, 1-naphthylboronic acid (19) for the coupling
reaction could readily be obtained from 1-bromonaphthalene
(18),22 which was prepared via bromination of NA tetralone23
followed by oxidation with DDQ. However, Hunsdiecker re-
actions with NA phthalic acid did not give consistent yields
of o-dibromobenzene (20), the coupling partner.24a,b Conse-
quently, we pursued pathway B, in which U-13C-bromobenzene
was treated with Li to generate phenyllithium for cou-
pling with 1, followed by dehydration to afford 4-phenyl-1,2-
dihydronaphthalene (21).25a,b Iodination and dehydrogenation of
21 to 2-iodo-1-phenylnaphthalene (22) was followed by Pd-
catalyzed migration and coupling to furnish fluoranthene (23) in
52% yield.
U-13C-Anthracene
(6):
U-13C-1,2,3,4,5,6,7,8-octahydro-
anthracene (112 mg, 0.56 mmol) was dissolved in benzene
(10 mL); DDQ (520 mg, 2.3 mmol) was added and the mixture
was refluxed for 1 h. After cooling to rt, the mixture was filtered
and washed with benzene. The combined filtrate was concentrated
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and purified by chromatography (Al2O3, benzene) to give a white
stirred at rt for 30 min. The mixture was then poured into ice and
extracted with CH2Cl2 (3 ¥ 25 mL). The extracts were washed with
water and brine, then dried over anhydrous Na2SO4. After removal
of solvent, the residue was further purified by chromatography
(SiO2, hexane) to give pyrene (290 mg, 64% in two steps). Mp
139–140 ◦C. GC-EIMS m/z 218 (M+, 100). UV-Vis lmax(ethanol)
◦
solid. (58 mg, 50%). Mp 203–205 C. GC-EIMS m/z 192 (M+,
100). UV-Vis lmax(ethanol) 251.5, 340.5, 357.0, 375.0 nm. 1H
NMR27 (300 MHz) d 8.44 (bd, J = 154.6 Hz, 2H, H9, H10), 8.00
(bd, J = 155.1 Hz, 4H, H1, H4, H5, H8), 7.48 (bd, J = 161.1 Hz,
4H, H2, H3, H6, H7). 13C NMR (100 MHz)1c d 133.1–130.8 (C4a,
C8a, C9a, C10a), 129.5–127.0 (m, C1, C4, C5, C8), 127.0–125.0
(m, C2, C3, C6, C7, C9, C10).
1
231.0, 240.0, 262.0, 272.0, 306.0, 319.0, 334.0 nm. H NMR1c,d
(400 MHz) d 8.16 (bd, J = 157.5 Hz, 4H, H1, H3, H6, H8), 8.05
(bd, J = 158.8 Hz, 4H, H4, H5, H9, H10), 7.98 (bd, J = 161.5 Hz,
2H, H2, H7). 13C NMR1c,d (100 MHz) d 132.3–130.5 (m, C3a,
C5a, C8a, C10a), 128.3–126.7 (m, C4, C5, C9, C10), 126.3–125.2
(m, C1–C3, C6–C8, C3a1, C5a1).
U-13C-Phenanthrene
(11):
U-13C-1,2,3,4-tetrahydro-
phenanthrene (224 mg, 1.1 mmol) was dissolved in triethylene
glycol dimethyl ether (5 mL), Pd–C (60 mg, 10% on charcoal)
was added. The mixture was heated to 240 ◦C under an argon
atmosphere for 4 h. After cooling to rt, the reaction mixture was
diluted with benzene (50 mL) and washed with water (10 ¥ 15 mL)
then brine (15 mL), and dried over anhydrous Na2SO4. The
solvent was removed and the residue crystallized from ethanol
to give 11 (172 mg, 78% yield). Mp 98–99 ◦C. GC-EIMS m/z
192 (M+, 100). UV-Vis. lmax (ethanol) 250.0, 274.0, 292.0 nm. 1H
NMR1c (500 Hz) 8.70 (bd, J = 160.2 Hz, 2H, H4, H5), 7.89 (bd,
J = 147.8 Hz, 2H, H1, H8), 7.74 (bd, J = 162.7 Hz, 2H, H9, H10),
7.66 (bd, J = 160.2 Hz, 2H, H2, H7), 7.60 (bd, J = 162.8 Hz, 2H,
H3, H6) 13C NMR1c (100 MHz) d 132.0–131.4 (m, C8a, C10a),
131.1–129.9 (m, C4a, C4b), 129.2–127.7 (m, C1, C8), 127.3–126.1
(m, C2, C3, C6, C7, C9, C10), 123.4–122.2 (m, C4, C5).
U-13C-Naphthalene (7): U-13C-Tetralone (243 mg, 1.6 mmol)
and diethyl sulfone (1.02 g, 8 mmol) were mixed in DMA (5 mL),
t-BuOK (1.8 g, 16 mmol) was added and the mixture heated under
argon at 150 ◦C over night. The reaction mixture was cooled and
partitioned into water (25 mL) and ether (50 mL). The organic
layer was washed extensively with water (5 ¥ 15 mL) and brine
(10 mL) and dried over anhydrous MgSO4. After evaporation
of solvent, the residue was purified by chromatography (SiO2,
hexane) to afford 7 (135 mg, 63% yield). Mp. 80–82 ◦C. GC-EIMS
1
m/z 138 (M+, 100). UV-Vis lmax(ethanol) 220.0, 266.0, 275.0. H
NMR29,30a,b (300 MHz) d 7.84 (bd, J = 160.9 Hz, 4H, H1, H4, H5,
H8), 7.49 (bd, J = 158.9 Hz, 4H, H2, H3, H6, H7) 13C NMR30a,b
(75 MHz) d 134.4–133.3 (m, C5a, C8a), 129.2–127.4 (m, C1, C4,
C5, C8) 127.8–125.7 (m, C2, C3, C6, C7).
Ethyl U-13C-2-(phenanthren-4-yl)acetate (13): To a mixture of
N-isopropylcyclohexylamine (0.75 mL, 4.5 mmol) in anhydrous
THF (5 mL) cooled at -78 ◦C under Ar, butyllithium (1.6
M in hexane, 2.5 mL, 4.0 mmol) was added. After stirring at
U-13C-Phthalic acid (15): Tetralone (255 mg, 1.64 mmol) was
mixed with water (20 mL), KMnO4 (1.44 g, 9.11 mmol) and KOH
(510 mg, 9.1 mmol) and the mixture refluxed overnight. After
cooling, methanol (2 mL) was added, followed by concd HCl
(10 mL). The clear solution was extracted with ether and the
extract was evaporated to afford a solid, which was washed with
methylene chloride to give 15 (164 mg, 58%). 1H NMR (300 MHz,
DMSO) d 7.76 (bd, J = 158.4 Hz, 2H, H3, H6), 7.63 (bd, J =
162.6 Hz, 2H, H4, H5).
◦
-78 C for 10 min, (1,2)-13C2-ethyl acetate (500 mg, 5.5 mmol)
in anhydrous THF (2 mL) was added dropwise. After addition
was complete, stirring was continued for 15 min. Compound 8
(500 mg, 2.45 mmol) in THF (5 mL) was added. The mixture was
stirred for 1 h. Concd HC1 (1 mL) in 10 mL of THF was added at
-78 ◦C to quench the reaction. The mixture was allowed to warm
to room temperature and partitioned into water (50 mL) and ether
(50 mL). The aqueous layer was extracted with ether (2 ¥ 25 mL)
and the combined extracts were washed with 5% HC1 (2 ¥ 15 mL),
water and brine, then dried over anhydrous MgSO4. Removal of
the ether afforded 12 as a yellowish oil. The crude product was
dehydrogenated as described above for 11 to give 13 (580 mg, 87%
in 2 steps). 1H NMR28 (400 MHz) d 8.56 (bd, J = 152.6 Hz, 1H,
H5¢), 7.87 (bd, J = 157.0 Hz, 1H, H8¢), 7.81 (bd, J = 159.4 Hz,
1H, H1¢), 7.68 (bd, J = 157.8 Hz, 2H, H9¢, H10¢), 7.52 (bd, J =
160.6 Hz, 4H, H2¢, H3¢, H6¢, H7¢), 4.40 (dd, J = 128.6, 6.8 Hz,
2H, ArCH2), 4.19 (dq, J = 7.2, 3.5 Hz, 2H, OCH2), 1.26 (t, J =
7.1 Hz, 3H, CH3). 13C NMR28 (100 MHz) d 171.9 (d, J = 59.8 Hz,
CO), 135.0–129.6 (m, C4¢, C4a¢, C4b¢, C8a¢, C10a¢), 129.5–125.6
(m, C1¢–C3¢, C5¢–C8¢, C9¢, C10¢), 44.3 (dd, J = 59.6, 40.2 Hz,
ArCH2).
U-13C-Benz[a]anthracene (17): A mixture of 16 and its a-isomer
(160 mg, 0.92 mmol), was dissolved in HI (5 mL) and HOAc
(10 mL) and refluxed for 2 d. After cooling, the mixture was poured
into water (100 mL) and extracted with CH2Cl2 (3 ¥ 40 mL). The
extract was washed with aqueous sodium sulfite (2 ¥ 10 mL), brine
and dried over anhydrous Na2SO4. After evaporation of solvent,
the residue was purified by chromatography (SiO2, hexane) to give
17 (70% in two steps). Mp 151–152 ◦C. GC-EIMS m/z 246 (M+,
100) UV-Vis. lmax (ethanol) 220.0, 256.0, 268.0, 277.0, 287.0, 299.5,
1
327.5, 341.5, 357.0 nm. H NMR31 (500 MHz) d 9.16 (bd, J =
161.3 Hz, 1H, H12), 8.83 (bd, J = 158.3 Hz, 1H, H1), 8.36 (bd, J =
159.1 Hz, 1H, H7), 8.11 (bd, J = 152.9 Hz, 1H, H8), 8.05–8.03 (bd,
J = 167.5 Hz, 1H, H11), 7.91–7.34 (m, 7H, H2–H6, H9, H10). 13
C
NMR32 (75 MHz) d 133.4–131.5 (m, C4a, C6a, C7a), 131.5–130.1
(m, C12a, C12b), 130.1–128.2 (m, C4, C8, C11a), 128.2–126.7 (m,
C2, C3, C5–C7, C11), 126.7–124.8 (m, C9, C10), 123.8–122.5 (m,
C1), 122.5–121.2 (m, C12).
U-13C-Pyrene (14): To a solution of 13 (560 mg, 2 mmol) in
dry toluene (30 mL), diisobu◦tylaluminium hydride (4 mL, 1 M
in hexane) was added at -78 C under Ar. The reaction mixture
was stirred for 1 h at -78 ◦C and the yellowish complex was
hydrolyzed by the addition of conc HC1 (1 mL) in THF (9 mL).
After warming to rt, the reaction mixture was washed with dilute
HCl and the organic layer dried over anhydrous MgSO4. Removal
of the toluene gave the aldehyde as a pale yellow oil. The crude
product was dissolved in anhydrous CH2Cl2 (8 mL) and cooled in
an ice bath, MSA (5 mL) was added slowly and the mixture was
U-13C-Fluoranthene (23): To a solution of 22 (346 mg,
1 mmol) in DMF (8 mL), Pd(OAc)2 (23 mg, 0.1 mmol), 1,1-
bis(diphenylphosphino)methane (dppm) (40 mg, 0.2 mmol) and
CsO2CCMe3 (468 mg, 0.2 mmol) were added. The reaction mixture
was stirred under argon at 110 ◦C for 12 h. After cooling, the
reaction mixture was diluted with ether (100 mL) and partitioned
into water. The aqueous layer was extracted with ether (25 mL)
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and the combined extracts were washed with HCl (0.5 M, 15 mL),
water (10 mL) and brine (15 mL) and dried over anhydrous
MgSO4. After evaporation of solvent, the residue was purified by
chromatography (SiO2, hexane) to give 23 (112 mg, 52% yield). Mp
103–105 ◦C GC-EIMS m/z 218 (M+, 100). UV-Vis lmax (ethanol)
9 (a) M. S. Newman and H V. Zahm, J. Am. Chem. Soc., 1943, 65, 1097;
(b) C. M. Daly, B. Iddon and H. Suschitzky, J. Chem. Soc., Perkin
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10 (a) A. Rahman, A. T. Vazquez and A. A. Khan, J. Org. Chem., 1963,
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Weingarten, J. Chem. Soc. C, 1971, 729.
1
235.0, 276.5, 281.5, 286.5, 322.5, 342.0, 358.0 nm. H NMR29
(300 MHz) d 7.94 (bd, J = 160.8 Hz, 4H, H1, H6, H7, H10), 7.85
(bd, J = 156.2 Hz, 2H, H3, H4), 7.65 (bd, J = 158.3 Hz, 2H, H2,
H5), 7.40 (bd, J = 159.9 Hz, 2H, H8, H9). 13C NMR33 (75 MHz) d
140.1–138.7 (m, C6b, C10a), 137.9–136.0 (m, C6a, C10b), 133.3–
131.4 (m, C10c), 130.1 (q, J = 54.6 Hz, C3a), 128.7–126.0 (m,
C2–C5, C8, C9), 122.1–120.9 (C7, C10), 120.1 (t, J = 55.6 Hz, C1,
C6).
11 (a) V. Premasagar, V. A. Palaniswamy and E. J. Eisenbraun, J.
Org. Chem., 1981, 46, 2974; (b) M. E. Isabelle, R. H. Wightman,
H. W. Avdovich and D. E. Laycock, Can. J. Chem., 1980, 58,
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12 (a) I. Agranat and Y.-S. Shih, Synthesis, 1974, 865; (b) I. Agranat, Y.
Bentor and Y.-S. Shih, J. Am. Chem. Soc., 1977, 99, 7068; (c) T. Mala’bi,
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