A convenient and general synthesis of cata- and peri-condensed polycyclic aromatic hydrocarbons with a Fjord-region

Article abstract of DOI:10.1055/s-2001-13401

Cata- and peri-condensed polycyclic aromatic hydrocarbons (PAHs) 10a-d and 11 have been conveniently synthesized by the application of Suzuki cross-coupling reaction. In three to four steps, these PAHs having fjord-region were obtained in an overall yield of 35-51% from commercially or easily accessible aryl boronic acids and aryl bromides.

Full text of DOI:10.1055/s-2001-13401

PAPER
841
A Convenient and General Synthesis of Cata- and Peri-Condensed Polycyclic
Aromatic Hydrocarbons with a Fjord-Region
A
Convenient
u
S
ynthesis of
b
Polynuclear
o
A
romatic
H
d
Environmental Toxicology and Chemistry Laboratory, Great Lakes Center, State University of New York College at Buffalo, 1300 Elm-
wood Avenue, Buffalo, New York 14222, USA
Fax +(716)8785400; E-mail: kumarsk@buffalostate.edu
Received 19 November 2000; revised 5 February 2001
The general method for the synthesis of PAHs (10a d and
Abstract: Cata- and peri-condensed polycyclic aromatic hydrocar-
11), outlined in the Scheme, began with the coupling of
commercially available aryl boronic acid (1 or 7) with aryl
bromides (2 6) in dry dimethoxyethane (DME) contain-
bons (PAHs) 10a d and 11 have been conveniently synthesized by
the application of Suzuki cross-coupling reaction. In three to four
steps, these PAHs having fjord-region were obtained in an overall
yield of 35 51% from commercially or easily accessible aryl bo- ing anhydrous CsF and Pd(PPh3)4 at reflux temperature.
ronic acids and aryl bromides.
This led, after 15 h, to the desired coupled products (8a
e) in 71 88% yields. Transformation of these aldehydes
into the corresponding ethylene epoxides (9a e) was first
examined using base-catalyzed reaction of trimethylsulfo-
nium iodide in the presence of a phase-transfer catalyst.6
However, the reaction was very slow, and required several
Key words: polycyclic aromatic hydrocarbons, aryl boronic acids,
Suzuki cross-coupling reaction, 2-(aryl)benzaldehyde, diben-
zo[c,mno]chrysene, naphtho[8,1,2-ghi]chrysene
Polycyclic aromatic hydrocarbons (PAHs) are widely dis- days to complete. Switching the reaction condition7 that
tributed environmental contaminants formed by incom- required the treatment of the aldehydes (8a e) with trim-
plete combustion of fossil fuels and other organic ethylsulfonium iodide and powdered KOH in acetonitrile
matters.1 Some of the PAHs, especially, those containing at 65 70 °C for 15 hours allowed the preparation of rela-
a fjord-region are relatively potent carcinogens.2,3 Devel- tively unstable ethylene epoxides (9a e) more efficiently
opment of methods for the synthesis of such PAHs has not in nearly a quantitative yield. The 1H NMR spectra of the
been properly addressed despite expanding interest in ethylene epoxides indicated the absence of an aldehydic
their chemistry and carcinogenic properties. The classical proton signal at ~ 9.7 ppm, and the presence of three pro-
methodologies,4 which are still widely applied to the syn- ton signals as double doublets between = 2.6 and 3.6
thesis of these chemicals, were developed prior to the ppm confirming the presence of ethylene epoxide func-
modern era of synthetic organic chemistry. These meth- tionality in these molecules. For the final step, a solution
ods frequently require multi-step, harsh reagents and con- of ethylene epoxides (9a d) in CH2Cl2 was treated with
ditions, and often result in the formation of mixtures that MeSO3H to form the corresponding PAHs (10a d) which
are difficult to separate. All these drawbacks lead to a low were conveniently purified by short-column chromatogra-
yield and to an increased exposure to these hazardous phy over dry column grade silica gel followed by recrys-
chemicals.
tallization. The crude product(s) 10e obtained after acid-
catalyzed cyclodehydration (MeSO3H/CH2Cl2) reaction
of 9e was treated with DDQ in refluxing benzene to pro-
duce naphtho[8,1,2-ghi]chrysene (11) in an overall 35%
We are interested in developing a general approach for the
synthesis of PAHs which is highly regiospecific, requires
fewer steps, and produces the potentially carcinogenic
PAH moiety in the last step. Consequently, we have in-
vestigated the potential application of the highly versatile
Suzuki cross-coupling reaction5 to develop a general route
for the synthesis of PAHs with a fjord-region. We now re-
port an efficient three- to four-step synthesis of ben-
zo[c]phenanthrene (10a), benzo[c]chrysene (10b),
benzo[g]chrysene (10c), dibenzo[c,mno]chrysene (10d),
and naphtho[8,1,2-ghi]chrysene (11) from commercial or
easily accessible starting materials. The synthesis of
dibenzo[c,mno)chrysene (10d) has not been reported in
the literature.
1
yield based on the aldehyde 8e. H NMR spectra of the
various PAHs synthesized were entirely consistent with
their assigned structures and, as expected, exhibited pro-
ton signals for sterically hindered bay-region or fjord-re-
gion protons significantly downfield compared to other
aromatic protons in these molecules. The synthesis of
PAH 10d has not been reported in the literature. However,
a product of photocyclization of 1,4-di-(2-naphthyl)-1,3-
butadiene or 4-(2-naphthyl)phenanthrene has been char-
acterized as 1111 based on its melting point, UV spectrum,
mass spectrum, and microanalysis. The melting point and
UV spectrum of 11 obtained in the current work were not
consistent with the reported values. However, a sample of
11 synthesized by Dr. A. Seidel (personal communica-
tion)12 had a melting point of 111 °C, and exhibited UV
and 1H NMR data identical to those reported in the present
study for 11.
Synthesis 2001, No. 6, 04 05 2001. Article Identifier:
1437-210X,E;2001,0,06,0841,0844,ftx,en;M03600SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

842
S. Kumar
PAPER
Scheme (i) Pd(PPh3)4, CsF, DME, reflux; (ii) Me3S+I–, KOH, MeCN, 65°C; (iii) MeSO3H, CH2Cl2; (iv) DDQ, C6H6, reflux
semisolid. For the majority of cases, the product was sufficiently
pure for the next step. A small sample of the product was chromato-
graphed over dry column grade silica gel. Elution with 2% EtOAc–
hexanes gave the aldehyde (8a e) which if solidified was recrystal-
lized from EtOAc–hexanes.
In summary, this three- to four-step synthetic route featur-
ing Suzuki cross-coupling reaction has readily furnished
the PAHs with a fjord-region in an overall yield of 35
51% based on the corresponding aldehydes. Currently, we
are extending this methodology to the synthesis of the car-
cinogenic metabolites of dibenzo[c,mno)chrysene (10d)
and naphtho[8,1,2-ghi]chrysene (11).
2-(1-Naphthyl)benzaldehyde (8a)
Purified by recrystallization from EtOAc–hexanes.
Yield: 95%; mp: 86 87 °C.
1H NMR: =7.36 7.99 (m, 10H), 8.12 (dd, 1H, J = 7.8, 1.5 Hz),
9.63 (s, 1H).
13C NMR: = 124.92, 125.67, 126.09, 126.67, 126.97, 128.08,
128.25, 128.54, 131.61, 132.59, 133.27, 133.55, 134.69, 135.30,
144.16, 192.01 (CHO).
MS: m/z = 232 (M+,28), 231 (50), 215 (10), 203 (28), 202 (46), 101
(100).
Naphthalene 1-boronic acid (1), 9-bromophenanthrene (3), 1-bro-
mopyrene (4), 2-formylphenylboronic acid (7), anhyd CsF, anhyd
dimethoxyethane (DME), and Pd(PPh3)4 were purchased from Ald-
rich Chemical Co., and used as such. 1-Bromophenanthrene (2) and
4-bromo-1,2,3,6,7,8-hexahydropyrene (5) were prepared according
to the method of Pan and Fletcher,8 and Konieczny and Harvey9, re-
spectively. Dry column grade silica gel was purchased from E. Mer-
ck.Mps are uncorrected. 1H and 13C NMR were obtained on Bruker
300 in CDCl3. Chemical shifts are in ppm relative to internal TMS
Anal. Calcd for C17H12O: C, 87.93; H, 5.17. Found: C, 88.34; H,
4.99.
1
for H NMR spectra and relative to solvent signals for 13C NMR
spectra. High resolution mass spectra were obtained at the mass
spectral facility of the Department of Chemistry, State University of
New York at Buffalo.
2-(1-Phenanthryl)benzaldehyde (8b)
Purified by column chromatography.
Oil; Yield: 92%.
2-(Aryl)benzaldehyde (8); General Procedure
1H NMR: =7.39 8.20 (m, 11H), 8.78 (d, 1H, J = 8.2 Hz), 8.83 (d,
1H, J = 8.5 Hz), 9.66 (s, 1H).
13C NMR: = 122.79, 122.98, 123.79, 125.56, 126.91, 127.02,
127.69, 128.09, 128.47, 128.65, 129.97, 130.29, 130.77, 131.49,
131.62, 133.56, 134.65, 135.91, 144.40, 191.88 (CHO).
MS: m/z 282 (M+, 97 ), 281 (100), 265 (23), 253 (33), 252 (51).
HRMS: Calcd for C21H14O (M+): 282.1044. Found: 282.1046.
A mixture of aryl boronic acid 1 (or 7) (0.011 mol), aryl bromide 6
(or 2 5) (0.01 mol), anhyd CsF (0.025 mol), and Pd(PPh3)4 (0.41 g,
0.00035 mol) in anhyd DME (50 mL) was stirred under reflux for
12 18 h in an Ar atm. The reaction was monitored by TLC (5%
EtOAc hexanes) until no more bromide was detected. The reaction
mixture was cooled and then extracted with a mixture of EtOAc–
H2O (1:1). The EtOAc layer was washed with 5% NaOH and H2O,
successively, to remove any unreacted boronic acid. After drying
(Na2SO4), the EtOAc solution was concentrated in vacuo to yield a
Synthesis 2001, No. 6, 841–844 ISSN 0039-7881 © Thieme Stuttgart · New York

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A Convenient Synthesis of Polycyclic Aromatic Hydrocarbons
843
2-(9-Phenanthryl)benzaldehyde (8c)
Purified by recrystallization from EtOAc–hexanes.
was cooled, and extracted with 10% NaOH followed by H2O. The
benzene solution was dried (Na2SO4), and concentrated to yield a
reddish oil which was chromatographed over dry-column grade sil-
ica gel using hexane as eluent to produce desired naphtho[8,1,2-
ghi]chrysene (11).
Yield: 92%; mp: 109 110 °C.
1H NMR: =7.40 7.82 (m, 9H), 7.90 (dd, 1H, J = 7.8, 1.2 Hz), 8.14
(dd, 1H, J = 7.8, 1.4 Hz), 8.75 (d, 1H, J = 8.1 Hz), 8.80 (d, 1H, 8.3
Hz), 9.72 (s, 1H).
Benzo[c]phenanthrene (10a)
13C NMR: = 122.49, 122.88, 126.71, 126.79, 126.97, 127.01,
127.05, 127.09, 128.18, 128.60, 128.98, 130.13, 130.79, 131.59,
131.78, 133.63, 133.98, 134.86, 144.07, 191.89 (CHO).
MS: m/z = 282 (M+, 41), 281 (71), 265 (10), 252 (40), 126 (100).
HRMS: Calcd for C21H14O (M+): 282.1044. Found: 282.1046.
Purified by chromatography using petroleum ether.
Yield: 45%; mp: 68 69 °C (Lit.4,10 mp: 68 °C).
1H NMR: = 7.59 7.72 (m, 4H), 7.83 (d, 2H, J = 8.5 Hz), 7.91 (d,
2H, J = 8.5 Hz), 8.03 (d, 2H, J = 7.6 Hz), 9.14 (d, 2H, J = 8.2 Hz).
Benzo[c]chrysene (10b)
Purified by chromatography using petroleum ether.
2-(1-Pyrenyl)benzaldehyde (8d)
Yield: 45%; mp: 126 127 °C (Lit.4 mp: 127 °C).
1H NMR: = 7.61 8.12 (m, 10H), 8.79 8.88 (m, 2H), 9.02 9.11
(m, 2H).
Purified by chromatography followed by recrystallization from
EtOAc–hexanes.
Yield: 8%; mp: 149 150 °C.
1H NMR: =7.56 8.28 (m, 13H), 9.65 (s, 1H).
13C NMR: = 124.18, 124.41, 124.44, 124.48, 125.25, 125.53,
126.20, 127.14, 127.17, 127.89, 128.10, 128.13, 128.29, 129.76,
130.64, 131.14, 131.27, 132.08, 132.47, 133.52, 134.82, 144.61,
191.98 (CHO).
Benzo[g]chrysene (10c)
Purified by chromatography using petroleum ether.
Yield: 51%; mp: 113 114 °C (Lit.4 mp: 114.5 °C).
1H NMR: =7.55 7.80 (m, 6H), 7.98 8.10 (m, 2H), 8.58 8.80 (m,
MS: m/z = 306 (M+, 18), 305 (11), 277 (21), 276 (16), 138 (100).
4H), 8.87 9.0 (m, 2H).
Anal. Calcd for C23H14O.1/10 EtOAc: C, 89.19; H, 4.70; Found: C,
88.97; H, 4.62.
Dibenzo[c,mno]chrysene (10d)
Purified by chromatography using petroleum ether.
Yield: 48%; mp: 166 168 °C (CH2Cl2).
2-(1,2,3,6,7,8-Hexahydro-4-pyrenyl)benzaldehyde (8e)
1H NMR: = 7.67 7.80 (m, 2H), 7.95 (d, 1H, J = 8.8 Hz), 8.01
8.22 (m, 6H), 8.28 (d, 1H, J = 7.7 Hz), 8.32 (d, 1H, J = 9.1 Hz), 8.55
(s, 1H), 9.25 (d, 1H, J = 8.4 Hz), 9.42 (d, 1H, J = 9.5 Hz).
13C NMR: = 124.47, 124.82, 124.91, 124.95, 125.08, 125.89,
126.11, 126.61, 126.83, 127.15, 127.20, 127.23, 127.46, 127.75,
128.22, 128.67, 129.65, 130.15 (2C), 130.59, 131.39, 133.06.
Purified by chromatography.
Oil; yield: 71%.
1H NMR: =1.89 2.00 (m, 2H), 2.05 2.14 (m, 2H), 2.61 2.82 (m,
2H), 3.03 3.14 (m, 6H), 7.08 (s, 1H), 7.18 7.24 (m, 2H), 7.37 (dd,
1H, J = 7.6, 0.7 Hz), 7.40 7.54 (m, 1H), 7.62 7.69 (m, 1H), 8.05
(dd, 1H, J = 7.9, 1.1 Hz), 9.78 (d, 1H, J = 0.7 Hz).
13C NMR: = 22.92, 23.10, 29.45, 31.16, 31.21, 123.93, 124.40,
125.70, 126.70, 127.53, 129.71, 129.74, 130.85, 131.75, 131.83,
133.52, 133.80, 133.86, 134.16, 134.32, 146.22, 192.41 (CHO).
MS: m/z = 312 (M+, 100), 294 (54), 283 (12), 266 (34), 253 (31),
239 (17).
HRMS: Calcd for C23H20O (M+): 312.1514. Found: 312.1504.
HRMS: Calcd for C24H14 (M+): 302.1095. Found: 302.1091.
Naphtho[8,1,2-ghi]chrysene (11)
Purified by chromatography using hexane.
Yield: 35%; mp: 109 110 °C (lit.11 mp: 278 280 °C; lit.12 mp:
111°C).
1H NMR: = 7.60 7.72 (m, 2H), 8.04 8.15 (m, 6H), 8.24 (d, 2H,
J = 7.6 Hz), 8.84 (d, 1H, J = 8.9 Hz), 8.93 (d, 1H, J = 8.0 Hz), 9.20
(apparent d, 1H, J = 7.6 Hz), 9.26 (d, 1H, J = 8.0 Hz).
Polycyclic Aromatic Hydrocarbons (10 and 11); General
Procedure
13C NMR:
= 120.54, 121.00, 123.90, 124.88, 125.02,
A mixture of the aldehyde 8 (0.01 mol) and trimethylsulfonium io-
dide (0.011 mol), and powdered KOH (0.04 mol) in MeCN (40 mL)
containing H2O (0.1 mL) was stirred under Ar at 65 70 °C for 16
h. The mixture was cooled, and extracted with EtOAc. The organic
phase was washed with H2O, dried (Na2SO4), and concentrated in
vacuo to yield nearly 10% of sufficiently pure, relatively unstable
ethylene oxide 9 as colorless syrupy oil.
125.42,125.57, 125.75, 125.82, 125.86, 126.20, 126.87, 127.28,
127.69, 128.02, 128.06, 128.28, 128.55, 129.02, 130.52, 130.98,
131.16, 133.51.
UV (95 % EtOH):
(0.42), 295 (0.40), 250 (0.23), 235 (0.23), 218 (0.75).
MS: m/z = 302 (M+, 100), 150 (23).
HRMS: Calcd for C24H14 (M+): 302.10955. Found: 302.10895.
nm (log ) = 357 (0.14), 342 (0.16), 306
max
The cyclization of ethylene oxide 9 (0.01 mol) was performed by
the dropwise addition of methanesulfonic acid (15 mL) in a solution
of CH2Cl2 (150 mL) at 0 °C under Ar. The solution was stirred at
r.t. for an additional 15 h at which time a significant formation of
relatively nonpolar product was observed by TLC (2% EtOAc–hex-
anes). The product was extracted twice with CH2Cl2, and the com-
bined organic extracts were successively washed with H2O, 10%
NaHCO3 and H2O. After drying the organic solution (Na2SO4), the
solvent was removed under reduced pressure, and the residue was
chromatographed over a short column of dry column grade silica
gel to produce 10.
References
(1) Harvey, R. G. Polycyclic Aromatic Hydrocarbons:
Chemistry and Carcinogenicity: Cambridge University
Press Cambridge: England, 1991, Chap. 3.
(2) Chang, H. F.; Cho, B. P. J. Org. Chem. 1999, 64, 9051.
(3) Agarwal, S. K.; Sayer, J. M.; Yeh, H. J. C.; Pannell, L. K.;
Hilton, B. D.; Pigott, M. A.; Dipple, A.; Yagi, H.; Jerina, D.
M. J. Am. Chem. Soc. 1987, 109, 2497.
The resulting product 10e (0.31 g, 1 mmol) and DDQ (4.0 mmol) in
anhyd benzene (20 mL) were refluxed for 5 h under Ar. The mixture
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S. Kumar
PAPER
(4) Harvey, R. G. Polycyclic Aromatic Hydrocarbons:
Chemistry and Carcinogenicity Cambridge University
Press: Cambridge, 1991, Chaps. 7–10.
(8) Pan, H.-L.; Fletcher, T. L. Synthesis 1973, 610.
(9) Konieczny, M.; Harvey, R. G. J. Org. Chem. 1979, 44, 2158.
(10) Cook, J. W. J. Chem. Soc. 1931, 2524.
(5) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(6) Kumar, S. J. Org. Chem. 1997, 62, 8535.
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Synthesis 2001, No. 6, 841–844 ISSN 0039-7881 © Thieme Stuttgart · New York