A practical, large-scale synthesis of pyrene-2-carboxylic acid

Article abstract of DOI:10.1055/s-0034-1379026

Pyrene-2-carboxylic acid is a versatile intermediate for introducing the unusual 2-pyrenyl unit into functional organic molecules. A classical preparation for this molecule has been revised and improved to give a robust and efficient three-step process. The method has been applied on a multigram scale to give pyrene-2-carboxylic acid in >70% overall yield from pyrene.

Full text of DOI:10.1055/s-0034-1379026

LETTER
▌2591
lAettePr ractical, Large-Scale Synthesis of Pyrene-2-Carboxylic Acid
Large-Scale Synthesis of Pyrene-2-Carboxylic Acid
Juan M. Casas-Solvas,1 Tiddo J. Mooibroek, Shugantan Sandramurthy, Joshua D. Howgego, Anthony P. Davis*
School of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, UK
Fax +44(117)9251295; E-mail: Anthony.Davis@bristol.ac.uk
Received: 09.07.2014; Accepted: 06.08.2014
E+
E+
Abstract: Pyrene-2-carboxylic acid is a versatile intermediate for
introducing the unusual 2-pyrenyl unit into functional organic mol-
ecules. A classical preparation for this molecule has been revised
and improved to give a robust and efficient three-step process. The
method has been applied on a multigram scale to give pyrene-2-car-
boxylic acid in >70% overall yield from pyrene.
9
10
8
6
1
3
7
2
5
4
Key words: condensed aromatic compounds, electrophilic aromat-
ic substitution, ring closure, ring opening, Haller–Bauer cleavage
E+
E+
Figure 1 Numbering system for pyrene 1, highlighting positions of
reactivity towards electrophiles
The pyrene nucleus occupies an important position in
photochemistry, molecular electronics and supramolecu-
lar chemistry. It possesses useful fluorescence properties2
which have been exceptionally well studied3 (indeed, it
has been called ‘the fruit fly of photochemists’4), and has
been widely used in biological probes and chemosensors.5
It also serves as a key component of many organic elec-
tronic systems, where it may appear either as a terminus
or a multivalent core unit.4 Its potential for π-stacking and
hydrophobic interactions has been used for non-covalent
attachment to carbon nanotubes6 and graphene,7 and for
binding to nucleic acids.8
1
2
Figure 2 Positioning the pyrene chromophore via C1 and C2 link-
ages. A 180° rotation about a C1 bond moves the chromophore by
several Å. The corresponding rotation about a C2 linkage has no ef-
fect, so conformations are more predictable.
The scope for exploiting pyrenes in these areas depends
strongly on the methodology available for the regioselec-
tive synthesis of derivatives. Electrophilic attack on
pyrene (1) is electronically favoured at positions 1, 3, 6
and 8 (see Figure 1), so substitution at one or all of these
positions is relatively straightforward.4,9,10 Consequently,
for example, a range of 1-substituted pyrenes are commer-
cially available for use as fluorescence tagging reagents.
However other substitution patterns are less accessible,
frequently requiring the application of indirect meth-
ods.11,12 In particular, obtaining pyrenes with functionality
at position 2 is much more difficult. This is significant for
two reasons. Firstly the position of substitution affects the
photophysical properties of the pyrene chromophore.13,14
Secondly, linkage via position 2 may be required for ar-
chitectural reasons, especially when higher symmetry is
required. This may, for instance, be important for chromo-
phore positioning; rotation of a pyrene unit about a C1
linkage moves the chromophore considerably, while rota-
tion about a C2 linkage has much less effect (see Figure
2).
Although a variety of methods have been reported for 2-
functionalised pyrenes, most involve multistep proce-
dures which do not seem convenient for large-scale use.
Examples include (a) the synthesis of cyclophanes fol-
lowed by valence isomerisation–dehydrogenation, (b)
photochemical cyclisation of 2,2′-divinylbiphenyls, (c)
thermal annulations of 2,2′-disubstituted dithiobenzylbi-
phenyls, (d) aromatisation of substituted 4,5,9,10-tetrahy-
dropyrenes, and (e) the transition-metal-catalysed
electrocyclisation of 2,6-diethynyl-1,1′-biphenyls.11,12 Di-
rect substitution at pyrene C2 is possible with very hin-
dered species, but most examples (e.g. the tert-butyl
cation15) do not lead to versatile intermediates. A notable
exception is the recent Ir(I)-catalysed borylation of pyrene
with bispinacolatodiborane, which is directed to positions
2 and 7 (presumably) by the hindered nature of the react-
ing complex.16,17 Given the range of transformations pos-
sible for arylboranes this procedure seems likely to be
widely useful.13,14,18 However, as described17 it employs a
glove box, and requires careful control to achieve just mo-
nosubstitution.
We recently required a large-scale supply of pyrene-2-
carboxylic acid (4; Scheme 1) as a starting point for recep-
tor synthesis. Notwithstanding its promise as a fluores-
cence tagging reagent and intermediate for other 2-
substituted pyrenes, this compound has received few men-
tions in the literature.8a,19 However, there was a three-step
SYNLETT 2014, 25, 2591–2594
Advanced online publication: 02.10.2014
DOI: 10.1055/s-0034-1379026; Art ID: st-2014-d0576-l
© Georg Thieme Verlag Stuttgart · New York
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2592
J. M. Casas-Solvas et al.
LETTER
procedure from pyrene dating from 1937 which seemed sequence and develop a version more suited to the modern
potentially viable.9,20 We now report an updated and im- laboratory.
proved version of this method, which is capable of provid-
ing 4 in >70% overall yield and on multigram scales (≥5
g using standard laboratory equipment). Despite the ad-
The conditions described by Vollmann et al. for the
Friedel–Crafts addition of phthalic anhydride to pyrene
involved AlCl3 as promoter in refluxing benzene.9 These
vent of newer methodology (see above) we believe this is
conditions did not give satisfactory results in our hands,
the most convenient and effective method for this com-
but the problem was readily solved by switching to di-
pound, and is competitive as an entry to a range of C2-
chloromethane as solvent. The revised procedure21 gave
functionalised pyrene derivatives.
highly pure 2 as a bright yellow solid in 98% isolated
yield. The identity of 2 was readily confirmed by the 1H
NMR spectrum (see Supporting Information), in which all
aromatic protons were inequivalent (excluding 2-substitu-
tion) and all showed at least one vicinal coupling (exclud-
HOOC
ing 4-substitution). For the conversion of 2 to diketone 3,
O
we again found Vollmann’s 1937 methodology inconve-
a
nient and difficult to reproduce. Treatment of 2 with ben-
a*
zoyl chloride in 1-chloronaphthalene did not yield the
reported9 precipitate of 3, and further handling of the mix-
ture was impeded by the high boiling point of the solvent
1
2
(256 °C). Instead, we employed PCl5 and AlCl3 in chloro-
benzene, as reported by Du et al. for a similar cyclisa-
tion.22 After evaporation of solvent and treatment of the
residue with water, diketone 3 was isolated by filtration as
a dark red solid, apparently pure by 1H NMR, and suitable
for direct use in the next step.23 Further purification could
be achieved by chromatography, but this procedure is less
suitable for large-scale use due to poor solubility of 3 in
the eluent (CH2Cl2–MeOH, 10:1). The structures of 2 and
3, previously established through classical arguments,
were confirmed by modern spectroscopic methods (see
Supporting Information).
b
b*
O
OH
O
O
c
c*
4
3
Scheme 1 Route to pyrene-2-carboxylic acid (4) reported in ref 9,
showing original reagents, conditions and yields (a–c) and the revised
versions developed in the present work (a*–c*). Original (1937) con-
ditions:9 (a) phthalic anhydride (1 equiv), AlCl3 (1.1 equiv), benzene
(3.7 mL/g), 40–50 °C, 1 h, yield not given; (b) benzoyl chloride (3
equiv), 1-chloronaphthalene (3.7 mL/g), reflux, 1 h, 53%; (c) molten
KOH (24 equiv), 195–215 °C, 30 min, then H2O (50 mL/g), 47–54%.
From the present work: (a*) phthalic anhydride (1 equiv), AlCl3 (2.5
equiv), CH2Cl2 (30 mL/g), reflux, 3 h, 98%; (b*) PCl5 (1.5 equiv),
AlCl3 (1.5 equiv), chlorobenzene (19 mL/g), reflux, 2.5 h, ca. quanti-
tative; (c*) t-BuOK (20 equiv), H2O (6 equiv), 1,2-dimethoxyethane
(14 mL/g), reflux, 7 h, 75% from 2.
The final step of the Vollmann procedure involves heating
3 with molten KOH at ca. 200 °C, effecting Haller–Bauer
cleavage24–27 as shown in Scheme 2. Of the four Ar–CO
bonds in 3 (a–d, see Scheme 2), it is necessary to break a
and c to yield the product 4. This outcome may be predict-
ed on the basis that (i) of the four options, pyrene C1 is
best able to support a negative charge, favouring cleavage
of a as the first step, and (ii) an ortho-carboxylate acceler-
ates bond-breaking, favouring c over d in the second
step.27 Nonetheless, the method of Vollmann did not give
especially good selectivity, affording 4 in 47–54% yield
along with a considerable amount of pyrene side-product.9
Moreover, the conditions applied would be difficult to
achieve with standard laboratory equipment. Recent work
on the Haller–Bauer cleavage has employed the milder
conditions of potassium tert-butoxide–water in polar
aprotic solvents,26,27 so we decided to test this methodolo-
gy in the present case. We were pleased to find that treat-
ment of 3 with H2O–tert-BuOK (molar ratio 3:10) in 1,2-
dimethoxyethane at ca. 85 °C for seven hours gave a
cleaner conversion to 4.28 Purification was achieved by (i)
trituration of the acidified crude product with water to re-
move benzoic and phthalic acid by-products, and (ii) short
column chromatography (30 mL silica gel per gram of
starting material) to remove pyrene and unreacted 3. On a
preparative scale (10 g of crude diketone 3) the method
gave 4 in 75% yield from 2. Pyrene (1) was isolated in just
The route to 4 discussed in this paper is summarised in
Scheme 1. Friedel–Crafts acylation of pyrene (1) with
phthalic anhydride gives the derivative 2 via attack at
pyrene C1 (as expected). This is followed by an intramo-
lecular Friedel–Crafts reaction which is directed towards
C2, presumably by steric effects. The resulting hexacyclic
diketone 3 is then treated with strong base, resulting in hy-
drolytic cleavage to pyrene-2-carboxylic acid (4). In the
original (1937) version due to Vollmann and co-workers,9
acid 4 was reported to be produced in an overall yield of
23%. Not only is this quite low, but some of the conditions
were unusual and inconvenient from a present-day view-
point [for example the use of chloronaphthalene as solvent
or molten KOH as a reaction medium; see Scheme 1, con-
ditions (a–c)]. We therefore decided to reinvestigate this
Synlett 2014, 25, 2591–2594
© Georg Thieme Verlag Stuttgart · New York

LETTER
Large-Scale Synthesis of Pyrene-2-Carboxylic Acid
2593
13% yield and 10% unreacted 3 could be recovered.28
Trace contaminants could be removed by recrystallisation
from nitrobenzene,9,20 but the material derived from the
column should be pure enough for most purposes (see
Figures S5 and S6, Supporting Information).
(3) Winnik, F. M. Chem. Rev. 1993, 93, 587.
(4) For a recent review covering the synthetic and application
aspects of pyrene, see: Figueira-Duarte, T. M.; Müllen, K.
Chem. Rev. 2011, 111, 7260.
(5) For a recent review on sensors and biological probes based
on pyrene, see: Karuppannan, S.; Chambron, J.-C. Chem.
Asian J. 2011, 6, 964.
(6) For example, see: (a) Tasis, D.; Tagmatarchis, N.; Bianco,
A.; Prato, M. Chem. Rev. 2006, 106, 1105. (b) Karousis, N.;
Tagmatarchis, N.; Tasis, D. Chem. Rev. 2010, 110, 5366.
(c) Le Goff, A.; Gorgy, K.; Holzinger, M.; Haddad, R.;
Zimmerman, M.; Cosnier, S. Chem. Eur. J. 2011, 17, 10216.
(d) Holzinger, M.; Baur, J.; Haddad, R.; Wang, X.; Cosnier,
S. Chem. Commun. 2011, 47, 2450. (e) Vriamont, C.;
Devillers, M.; Riant, O.; Hermans, S. Chem. Eur. J. 2013,
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c
O
O
d
b
COOK
O
a
a
c
3
5
(7) For example, see: (a) Xu, Y.; Bai, H.; Lu, G.; Li, C.; Shi, S.
J. Am. Chem. Soc. 2008, 130, 5856. (b) Kodali, V. K.;
Scrimgeour, J.; Kim, S.; Hankinson, J. H.; Carroll, K. M.; de
Heer, W. A.; Berger, C.; Curtis, J. E. Langmuir 2011, 27,
863. (c) Mann, J. A.; Rodríguez-López, J.; Abruña, H. D.;
Dichtel, W. R. J. Am. Chem. Soc. 2011, 133, 17614. (d) Li,
Y.-J.; Ma, M.-J.; Yin, G.; Kong, Y.; Zhu, J.-J. Chem. Eur. J.
2013, 19, 4496.
d
O
OK
(8) For example, see: (a) Wu, J. C.; Zou, Y.; Li, C. Y.; Sicking,
W.; Piantanida, I.; Yi, T.; Schmuck, C. J. Am. Chem. Soc.
2012, 134, 1958. (b) Printz, M.; Richert, C. Chem. Eur. J.
2009, 15, 3390. (c) Endo, M.; Sugiyama, H. ChemBioChem
2009, 10, 2420. (d) Astakhova, I. V.; Korshun, V. A.;
Wengel, J. Chem. Eur. J. 2008, 14, 11010.
(K+ salt)
1
4
Scheme 2 Base-induced Haller–Bauer cleavage of 1,2-phtha-
loylpyrene (3). In the first step cleavage of a is promoted by the ability
of pyrene C1 to support a negative charge, while in the second step
the CO2– group in 5 accelerates cleavage of c with respect to d.
(9) Vollmann, H.; Becker, H.; Corell, M.; Streeck, H. Justus
Liebigs Ann. Chem. 1937, 531, 1.
(10) Ogino, K.; Iwashima, S.; Inokuchi, H.; Harada, Y. Bull.
Chem. Soc. Jpn. 1965, 38, 473.
(11) For a recent review covering the synthesis of substituted
pyrenes by indirect methods, see: Casas-Solvas, J. M.;
Howgego, J. D.; Davis, A. P. Org. Biomol. Chem. 2014, 12,
212.
(12) Walker, D. B.; Howgego, J.; Davis, A. P. Synthesis 2010,
3686.
(13) Wanninger-Weiß, C.; Wagenknecht, H.-A. Eur. J. Org.
Chem. 2008, 64.
(14) Crawford, A. G.; Dwyer, A. D.; Liu, Z.; Steffen, A.; Beeby,
A.; Pålsson, L.-O.; Tozer, D. J.; Marder, T. B. J. Am. Chem.
Soc. 2011, 133, 13349.
(15) Berg, A.; Jakobsen, H. J.; Johansen, S. R. Acta Chem. Scand.
1969, 23, 567.
(16) Coventry, D. N.; Batsanov, A. S.; Goeta, A. E.; Howard, J.
A. K.; Marder, T. B.; Perutz, R. N. Chem. Commun. 2005,
2172.
(17) Crawford, A. G.; Liu, Z. Q.; Mkhalid, I. A. I.; Thibault, M.
H.; Schwarz, N.; Alcaraz, G.; Steffen, A.; Collings, J. C.;
Batsanov, A. S.; Howard, J. A. K.; Marder, T. B. Chem. Eur.
J. 2012, 18, 5022.
In conclusion, a classical but somewhat impractical syn-
thesis of pyrene-2-carboxylic acid (4) has been updated
and improved such that it can be applied conveniently and
efficiently in a modern laboratory. The method has been
tested on a multigram scale by several workers, yielding
the product 4 in >70% overall yield from pyrene. By pro-
viding easy access to 4, this work should facilitate the use
of 2-pyrenyl units in the design of sensors, receptors and
other functional organic molecules.
Acknowledgment
This work was supported by the Engineering and Physical Sciences
Research Council through grant number EP/I028501/1, and the 7th
Framework Program of the European Commission (Marie Curie
Intra-European Fellowship for Career Development to J.M.C.-S.).
We thank Prof. Andrew Benniston for helpful advice and a sample
of pyrene-2-carboxylic acid.
Supporting Information for this article is available online
(18) Colquhoun, H. M.; Zhu, Z.; Williams, D. J.; Drew, M. G. B.;
Cardin, C. J.; Gan, Y.; Crawford, A. G.; Marder, T. B. Chem.
Eur. J. 2010, 16, 907.
at
http://www.thieme-connect.com/products/ejournals/journal/
10.1055/s-00000083.SunpfgIpi
o
o
nr
i
(19) For example, see: (a) Benniston, A. C.; Harriman, A.;
Howell, S. L.; Sams, C. A.; Zhi, Y.-G. Chem. Eur. J. 2007,
13, 4665. (b) Glatt, H.; Rost, K.; Frank, H.; Seidel, A.;
Kollock, R. Archiv. Biochem. Biophys. 2008, 477, 196.
(c) Villalonga, R.; Diez, P.; Gamella, M.; Reviejo, J.;
Pingarron, J. M. Electroanalysis 2011, 23, 1790.
(d) Lercher, L.; McGouran, J. F.; Kessler, B. M.; Schofield,
C. J.; Davis, B. G. Angew. Chem. Int. Ed. 2013, 52, 10553.
References and Notes
(1) New address: Department of Chemistry and Physics,
University of Almería, Carretera de Sacramento s/n, 04120
Almería, Spain.
(2) Berlman, I. B. Handbook of Fluorescence Spectra of
Aromatic Molecules; Academic Press: New York, 1971.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2591–2594

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J. M. Casas-Solvas et al.
LETTER
(20) For a repetition of the procedure in ref. 9, without significant
modifications, see: Barfield, M.; Collins, M. J.; Gready, J.
E.; Sternhell, S.; Tansey, C. W. J. Am. Chem. Soc. 1989, 111,
4285.
(21) Preparation of 1-(o-Carboxybenzoyl)pyrene (2): AlCl3
(15.4 g, 116 mmol) was added to a suspension of pyrene (9.4
g, 46 mmol) and phthalic anhydride (6.9 g, 46 mmol) in
anhyd CH2Cl2 (280 mL) under N2 atmosphere. The mixture
was heated under reflux for 3 h. The solvent was then
evaporated and the residue was cooled to 0 °C and
J = 7.6, 0.9 Hz, 1 H, H-6′), 8.24 (d, 3J = 9.8 Hz, 1 H, H-9),
8.21 (d, 3J = 7.5 Hz, 1 H, H-8), 8.18 (d, 3J = 7.5 Hz, 1 H, H-
6), 8.13 (d, 3J = 8.9 Hz, 1 H, H-5), 8.09 (d, 3J = 8.9 Hz, 1 H,
H-4), 8.02 (t, 3J = 7.5 Hz, 1 H, H-7), 7.80 (dt, J = 7.5, 1.2 Hz,
1 H, H-4′), 7.75 (dt, J = 7.5, 1.2 Hz, 1 H, H-5′). 13C NMR
(125 MHz, CDCl3): δ = 185.9 [C-1(CO)C-2′], 184.3 [C-
2(CO)C-1′], 136.2 (C-2′), 135.0 (C-3a), 134.4 (C-4′), 133.5
(C-5′), 133.1 (C-1′), 132.0 (C-2), 131.9 (C-9), 131.8 (C-5a),
131.7 (C-10a), 131.2 (C-5), 131.0 (C-8a), 128.3 (C-4), 127.8
(C-7), 127.7 (C-3a1), 127.6 (C-3′), 127.5 (C-6), 127.1 (C-8),
126.8 (C-6′), 126.5 (C-10), 124.3 (C-1), 124.2 (C-3), 123.8
(C-5a1). HRMS (EI+): m/z [M]+ calcd for C24H12O2:
332.0837; found: 332.0842.
suspended in H2O (500 mL). The pH of the solution was
adjusted to 0–1 by adding concd aq HCl (20 mL), and the
solid was isolated by filtration, washed with ice water (2 ×
150 mL) and dried by addition–evaporation of toluene. The
solid was suspended in glacial AcOH (500 mL) and heated
at 130 °C for 5 min, after which the insoluble material was
removed by hot filtration and washing with hot glacial
AcOH (3 × 50 mL). The filtrate was poured into ice water (1
L) and the resulting solid was isolated by filtration, washed
with ice water (2 × 100 mL) and dried by addition–
(24) Gilday, J. P.; Paquette, L. A. Org. Prep. Proced. Int. 1990,
22, 167.
(25) Mehta, G.; Venkateswaran, R. V. Tetrahedron 2000, 56,
1399.
(26) Davies, D. G.; Derenber, M.; Hodge, P. J. Chem. Soc. C
1971, 455.
(27) Davies, D. G.; Hodge, P. J. Chem. Soc. C 1971, 3158.
(28) Preparation of Pyrene-2-carboxylic Acid (4): Crude 3 (10
g) was suspended in 1,2-dimethoxyethane (140 mL). H2O (3
equiv per carbonyl group, 3.3 mL, 180.6 mmol) was added,
then potassium tert-butoxide (10 equiv per carbonyl group,
67.6 g, 602 mmol) was added portionwise with vigorous
stirring to ensure that a fine suspension was maintained
throughout the addition. The mixture was vigorously stirred
under reflux for 7 h and the solvent was evaporated. The
residue was cooled to 0 °C, suspended in H2O (1 L), and
acidified to pH 1–2 with concd aq HCl. The resulting solid
was removed by filtration, suspended in H2O (2 L), stirred
overnight, collected by filtration, washed with H2O (2 × 250
mL) and dried in vacuo. The material was ground into a fine
powder then slowly added to CH2Cl2–MeOH (1:1, 250 mL),
forming a suspension. Silica (30 g) was then added and the
mixture was concentrated to dryness. The resulting fine
powder was carefully loaded (band height = 1.8 cm) on a
short column (diameter = 6.5 cm, ca. 300 mL, silica gel,
height = 5 cm) packed with CH2Cl2–hexane (1:1). Pyrene (1;
0.79 g, 3.9 mmol, 13% from 2) and starting diketone 3 (0.96
g, 2.9 mmol, 10% from 2) eluted with CH2Cl2–hexane (1:1,
500 mL) and CH2Cl2 (1.5 L), respectively. The polarity of
the eluent was increased to 10% MeOH in CH2Cl2 (150 mL
per 2.5% increment) and finally to CH2Cl2–MeOH–30% aq
NH3 (90:9:1, 2 L) to elute the product. Elution of diketone 3
(bright yellow/orange fluorescence) and product 4 (dark
purple fluorescence) could be monitored by irradiating the
column with a 365 nm UV lamp. Pyrene-2-carboxylic acid
(4; 5.46 g, 22.2 mmol, 75% from 2) was obtained as a light
grey solid; mp 326 °C (Lit.9 326 °C); Rf = 0.33 (CH2Cl2–
MeOH, 10:1). FTIR (ATR): 2596, 1685, 1305, 1247, 896,
840, 820, 704 cm–1. 1H NMR (400 MHz, DMSO-d6): δ =
13.31 (br s, 1 H, COOH), 8.86 (s, 2 H, H-1, H-3), 8.33 (d,
3J = 7.6 Hz, 2 H, H-6, H-8), 8.31 (d, 3J = 9.2 Hz, 2 H, H-4,
H-10), 8.24 (d, 3J = 9.2 Hz, 2 H, H-5, H-9), 8.13 (t, 3J = 7.6
Hz, 1 H, H-7). 13C NMR (100 MHz, DMSO-d6): δ = 167.8
(COOH), 131.2 (C-5a, C-8a), 130.5 (C-3a, C-10a), 128.1 (C-
2), 128.0 (C-5, C-9), 127.7 (C-4, C-10), 127.3 (C-7), 125.8
(C-3a1), 125.5 (C-1, C-3, C-6, C-8), 123.3 (C-5a1). HRMS
(ESI–): m/z [M – H]– calcd for C17H9O2: 245.0608; found:
245.0615.
evaporation of toluene to give 2 (15.96 g, 45.6 mmol, 98%)
as a bright yellow powder; mp 224–225 °C (Lit.9 mp 225–
226 °C); Rf = 0.35 (CH2Cl2–MeOH, 10:1). FTIR (ATR):
3039, 2910, 2786, 2617, 2546, 2492, 1714, 1591, 1578,
1234, 941, 838, 708 cm–1. 1H NMR (500 MHz, DMSO-d6):
δ = 13.01 (br s, 1 H, COOH), 9.18 (d, 3J = 9.2 Hz, 1 H, H-
10), 8.41 (d, 3J = 9.2 Hz, 1 H, H-9), 8.40 (br d, J = 7.6 Hz, 2
H, H-6, H-8), 8.32 (d, 3J = 9.1 Hz, 1 H, H-5), 8.21 (d, 3J =
8.1 Hz, 1 H, H-3), 8.18 (d, 3J = 9.1 Hz, 1 H, H-4), 8.15 (t, 3J
= 7.6 Hz, 1 H, H-7), 7.99 (br d, J = 7.6 Hz, 1 H, H-6′), 7.83
(d, 3J = 8.1 Hz, 1 H, H-2), 7.77 (ddd, J = 7.6, 7.2, 1.2 Hz, 1
H, H-4′), 7.71 (ddd, J = 7.6, 7.2, 1.2 Hz, 1 H, H-5′), 7.63 (br
d, J = 7.2 Hz, 1 H, H-3′). 13C NMR (125 MHz, DMSO-d6):
δ = 198.7 (CO), 167.5 (COOH), 142.9 (C-2′), 133.5 (C-3a),
132.1 (C-4′), 131.1 (C-1), 130.8 (C-1′), 130.6 (C-5a), 130.3
(C-5′), 130.0 (C-8a), 129.9 (C-5), 129.8 (C-10a), 129.7 (C-
6′), 129.5 (C-9), 128.9 (C-2), 128.5 (C-3′), 127.2 (C-4),
126.8 (C-7), 126.7 (C-6), 126.3 (C-8), 125.1 (C-10), 124.1
(C-3a1), 123.9 (C-3), 123.3 (C-5a1). HRMS (ESI–): m/z [M –
H]– calcd for C24H13O3: 349.0870; found: 349.0881.
(22) Du, C.; Guo, Y.; Liu, Y.; Qiu, W.; Zhang, H.; Gao, X.; Liu,
Y.; Qi, T.; Lu, K.; Yu, G. Chem. Mater. 2008, 20, 4188.
(23) Preparation of 1,2-Phthaloylpyrene (3): 1-(o-Carboxy-
benzoyl)pyrene (2; 16.0 g, 45.7 mmol) was suspended in
chlorobenzene (300 mL) under N2 atmosphere, and PCl5
(14.44 g, 69.3 mmol) and AlCl3 (9.58 g, 71.9 mmol) were
added. The resulting dark green mixture was heated under
reflux for 2.5 h. The solvent was removed by evaporation
and the residue was cooled to 0 °C and suspended in H2O
(450 mL). The dark red precipitate was collected by
filtration, washed with H2O (4 × 100 mL), toluene was added
and evaporated (3 × 200 mL), and the resulting solid was
further dried in vacuo (overnight) to give 3 (15.5 g, ca.
quantitative). This material appeared pure by 1H NMR and
was used directly in the next step. Trace amounts of a highly
coloured contaminant were removed by flash chromatog-
raphy (CH2Cl2–hexane, 1:1 → CH2Cl2–MeOH, 10:1) to give
a sample for characterisation; mp 255–256 °C (Lit.9 254 °C);
Rf = 0.51 (EtOAc–hexane, 1:4). FTIR (ATR): 3119, 3024,
2804, 1716, 1661, 1615, 1443, 1392, 620 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 9.87 (d, 3J = 9.8 Hz, 1 H, H-10), 8.90
(s, 1 H, H-3), 8.34 (dd, J = 7.6, 0.9 Hz, 1 H, H-3′), 8.28 (dd,
Synlett 2014, 25, 2591–2594
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