Synthesis of benzo[a]pyren-6-yl-substituted carboxylic acids

Article abstract of DOI:10.1002/ejoc.200300217

The title compounds were synthesized from benzo[a]pyrene in three to four steps, depending on the chain length of the carboxylic acid. After iodination, alkanone chains were introduced by special Heck reactions. Transformation into carboxylic acids was achieved by haloform reaction and by Willgerodt-Kindler reaction. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200300217

FULL PAPER
Synthesis of Benzo[a]pyren-6-yl-Substituted Carboxylic Acids
Gerald Dyker*[a] and Daniel Kadzimirsz[a]
Keywords: Carboxylic acids / Haloform reaction / Nitrogen heterocycles / Palladium / Rearrangement
The title compounds were synthesized from benzo[a]pyrene
in three to four steps, depending on the chain length of the
carboxylic acid. After iodination, alkanone chains were intro-
duced by special Heck reactions. Transformation into carb-
oxylic acids was achieved by haloform reaction and by
Willgerodt−Kindler reaction.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
The Heck reaction with allylic and homoallylic alcohols
such as 3a (n ϭ 0) and 3b (n ϭ 1) is a well established
method for the introduction of alkanone chains,[10Ϫ12] and
the B[a]P derivatives 4 were indeed also obtained in good
to excellent yields (Scheme 1). The initial carbopalladation
Benzo[a]pyrene (1) Ϫ abbreviated as B[a]P Ϫ is one of
the most potent carcinogenic polycyclic aromatic
hydrocarbons.[1Ϫ3] Analytical chemistry is therefore in need
of methods that will allow the reliable measurement of its
concentration in water in the range of less than 10 ng/l. An
appropriate immunoassay should be the method of choice.
For the generation of monoclonal antibodies with the re-
quired selectivity for 1, immunogens made from suitable
B[a]P derivatives are indispensable, and the title compounds
are promising candidates for this purpose. Here we report
on the synthesis of the three homologous B[a]P-substituted
carboxylic acids 6, 7 and 8. For comparison, related studies
for the generation of monoclonal antibodies for 1 have also
employed alkanoic acids, but either with B[a]Ps substituted
in the 1-position[4] or with disadvantageous heteroatoms in
the chain.[5]
Results and Discussion
The 6-position of B[a]P (1) is the most electrophilic, but
is sterically somewhat hindered.[6Ϫ8] Nevertheless, our in-
tention was to introduce a sterically rather demanding iod-
ine into the 6-position, in order to make use of Heck-type
reactions for the introduction of a functionalized side chain.
Alternative methods for the final transformation into a car-
boxylic acid should give access to a variety of model com-
pounds with different chain lengths.
Initial attempts to iodinate 1 with iodide under acidic
conditions as described by Tye et al.[9] were unsatisfactory
in our hands because of insufficient regioselectivity. N-iodo-
succinimide (NIS) supported by acidic aluminium oxide
turned out to be a superior reagent, giving access to 6-iodo-
B[a]P (2) in 80% yield.
Scheme 1. a: NIS, Al2O3, toluene 20 °C, 4 days, 80%; b: 3,
Pd(OAc)2, LiCl, NEt3, DMF, 120 °C, 14 h, n ϭ 0: 76%, n ϭ 1:
94%; c: sulfur, morpholine, 140 °C, 6 h, n ϭ 0: 39%, n ϭ 1: 19%; d:
Br2, NaOH, dioxane, 20 °C, 6 h, 56%; e: KOH, 2-methoxyethylene
glycol, reflux, 6 h, n ϭ 0: 39%, n ϭ 1: 58%
[a]
Fakultät für Chemie, Ruhr-Universität Bochum,
Universitätsstrasse 150, 44780 Bochum, Germany
Fax: (internat.) ϩ49-(0)234/3214353
E-mail: Gerald.Dyker@rub.de
Eur. J. Org. Chem. 2003, 3167Ϫ3172
DOI: 10.1002/ejoc.200300217
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3167

G. Dyker, D. Kadzimirsz
FULL PAPER
of this process regularly takes place highly regioselectively, this chain seem to be necessary for the observed inertness.
with CϪC bond formation at the terminal olefinic carbon. Compound 4b also proved to be inert for the iodoform re-
However, a small amount of less than 3% of the isomeric action[19] under moderate conditions with either KOH or
alcohol 9 was also isolated and characterized (Scheme 2).
with pyridine as base. Under forced reaction conditions
with potassium tert-butoxide as a stronger base in refluxing
tert-butanol, a monoiodination obviously takes place, since
the only isolated product 11 clearly derives from a Favor-
skii rearrangement.[20Ϫ22]
The failure of the haloform reactions in the case of 4b
made us look for an alternative pathway to the butanoic
acid 7. The WilgerodtϪKindler reaction is a rather complex
domino process, involving several redox reaction steps in an
alkanone chain; after hydrolysis of an thioamide as inter-
mediary product one obtains a carboxylic acid with the
same number of carbon atoms as the initial alkanone.[23Ϫ24]
The oxidizing conditions of this process are compatible
with the sensitive B[a]P nucleus.[25] Therefore, butanone 4a
was chosen as starting material for the desired butanoic
acid 7, and indeed, heating of 4a with sulfur in morpholine
at 140 °C resulted in the formation of the thioamide 5a as
the main product in moderate yield, with the terminal car-
bon atom already in the right oxidation state. The thio-
phene 12, isolated in 15% yield, is a regular by-product of
this kind of process. For the hydrolysis of 5a, rather vigor-
ous reaction conditions were necessary: potassium hydrox-
ide in boiling 2-methoxyethanol was the reagent of choice.
After chromatography over silica, the butanoic acid 7 was
obtained in 39% yield. The analogous transformation of
pentanone 4b into the pentanoic acid 8 was also successful,
but 4b was also the substrate that caused the most problems
in the WillgerodtϪKindler process. TLC showed that a
multitude of products were formed, from which 13 and 14
were identified and characterized in addition to the 19%
yield of the desired product 5b. Luckily, the final hydrolysis
step Ϫ although again under harsh conditions Ϫ proceeded
with satisfactory results.
Scheme 2. Isolated and characterized by-products
In order to transform the obtained alkanones 4 into the
desired carboxylic acids we planned to make use both of
the haloform reaction[13Ϫ15] and of the WilgerodtϪKindler
reaction.[16Ϫ18] The propanoic acid 6 was obtained from the
bromoform reaction of the butanone 4a (n ϭ 0) in an ac-
ceptable yield, an aqueous hypobromide solution, freshly
prepared from bromine, KOH and water and mixed with
dioxane, being applied at 0 °C in this case. Surprisingly,
pentanone 4b (n ϭ 1) was completely inert under the same
reaction conditions. An increase in the amount of bromine,
though, gave a 71% yield of the barely soluble dibromide
10. The reasons for the inertness of the α-acidic protons of
4b remains unclear: there is no obvious increase in steric
hindrance in relation to 4a. Actually, one would assume a
higher reactivity for 4b, since the distance of the keto func-
tionality from the sterically demanding aromatic moiety is
larger than in the case of 4a. For comparison we synthe-
sized the pyranyl-substituted pentanone 16 (as outlined in
Scheme 3), which smoothly underwent the bromoform reac-
tion under moderate conditions. Both the particular length
of the pentanone moiety and the double peri-position of
Conclusion
The overall yields, starting from the parent compound 1,
are 15% for the propanoic acid 6, 46% for the butanoic acid
7 and 17% for the pentanoic acid 8. The procedures pre-
sented are suitable for synthesis of B[a]P-substituted car-
boxylic acids on 100 mg scales in one run. The synthesized
B[a]P derivatives 6, 7 and 8 are designated for the develop-
ment of a potent immunoassay based on monoclonal anti-
bodies.
Experimental Section
General Remarks: M.p. (uncorrected): Reichert Thermovar. IR:
PerkinϪElmer 841. NMR: Bruker DRX 400. 1H NMR spectra
(400 MHz) were recorded in CDCl3, (CD3)2CO or [D6]DMSO (7a,
7b) with TMS as the internal standard. 13C NMR spectra
(100.6 MHz) were measured by use of CDCl3, (CD3)2CO or
[D6]DMSO as the solvent and the internal standard. The assign-
ments of the 1H NMR and 13C NMR signals are based on 2D
Scheme 3. Model study starting from pyrene: sequence of Heck
reaction and haloform reaction; a: 3b, Pd(OAc)2, LiCl, NEt3,
DMF, 120 °C, 14 h, n ϭ 1: 63%; b: Br2, NaOH, dioxane, 20 °C,
6 h, 79%
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Eur. J. Org. Chem. 2003, 3167Ϫ3172

Synthesis of Benzo[a]pyren-6-yl-Substituted Carboxylic Acids
FULL PAPER
NMR techniques such as HMBC, HMQC and H,H COSY. MS:
MAT 700 ITD (70 eV) and Varian MAT 311 A. For analytical
TLC, precoated plastic sheets ‘‘POLYGRAM SIL G/UV254’’ from
MachereyϪNagel were used. EA: Elementar/Hanau Vario EL.
(270 mg, 0.70 mmol) and the homoallylic alcohol 3b, compound 4b
(220 mg, 0.66 mmol, 94%) and the by-product
9 (4Ϫ5 mg,
0.015 mmol, 2%) were obtained. Rf ϭ 0.65 (silica, ethyl acetate/
petroleum ether, 1:3). IR (KBr): ν˜ ϭ 3039 cmϪ1 (w), 2925 (w), 2866
(w), 1717 (vs), 1461 (m), 1243 (m), 837 (m), 754 (s), 695 (m). 1H
NMR (400 MHz, CDCl3): δ ϭ 2.15Ϫ2.23 (m, 2 H, 4Ј-H), 2.17 (s,
3 H, 1Ј-H), 2.66 (t, J ϭ 6.9 Hz, 2 H, 3Ј-H), 3.75Ϫ3.79 (m, 2 H, 5Ј-
H), 7.80Ϫ7.85 (m, 2 H, 8-H, 9-H), 7.95 (dd, J ϭ 7.8, 7.3 Hz, 1 H,
2-H), 7.95 (d, J ϭ 9.0 Hz, 1 H, 12-H), 8.06 (dd, J ϭ 7.4, 1.0 Hz, 1
H, 1-H), 8.19 (dd, J ϭ 7.8, 1.0 Hz, 1 H, 3-H), 8.26 (d, J ϭ 9.4 Hz,
1 H, 4-H), 8.32 (d, J ϭ 9.4 Hz, 1 H, 5-H), 8.60Ϫ8.62 (m, 1 H, 7-
H), 9.04 (d, J ϭ 9.0 Hz, 1 H, 11-H), 9.09Ϫ9.10 (m, 1 H, 10-H)
ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 25.0 (t, C-4Ј), 27.5 (t, C-
5Ј), 30.2 (q, C-1Ј), 43.2 (t, C-3Ј), 122.2 (d, C-11), 123.7 (d, C-10),
123.9 (s, C-12c), 124.5 (d, C-5), 124.7 (d, C-1), 125.1 (d, C-7), 125.7
(2d, C-3,C-9), 126.1 (d, C-2), 126.3 (d, C-8), 126.6 (s, C-10b), 127.0
(d, C-4), 127.0 (s, C-12b), 127.4 (s, C-5a), 128.1 (d, C-12), 128.3 (s,
C-10a), 130.0 (s, C-6a), 131.3 (s, C-3a), 131.6 (s, C-12a), 132.7 (s,
C-6), 208.7 (s, C-2Ј) ppm. MS (EI): m/z (%) ϭ 336 (39) [Mϩ], 278
(16), 265 (100), 251 (3), 250 (2), 43 (5).
By-Product 9: Rf ϭ 0.48 (silica, ethyl acetate/petroleum ether, 1:3).
IR (KBr): ν˜ ϭ 2964 cmϪ1 (m), 2930 (m), 2858 (w), 1458 (m), 1262
(m), 840 (s), 828 (m), 760 (s), 702 (m). 1H NMR (400 MHz,
CDCl3): δ ϭ 1.17 (d, J ϭ 6.0 Hz, 3 H, 1Јa-H), 1.21 (d, J ϭ 6.0 Hz,
3 H, 1Јb-H), 2.13 (s, 1 H, OH), 2.81 (‘‘t’’, J ϭ 6.8 Hz, 2 H, 3Ј-H),
3.88Ϫ3.95 (m, 2 H, 2Ј-H), 5.46 (d, J ϭ 3.0 Hz, 1 H, 5aЈ-H), 5.99
(d, J ϭ 3.0 Hz, 1 H, 5bЈ-H), 7.80 (‘‘t’’, J ϭ 7.7 Hz, 1 H, 8-H), 7.83
(‘‘t’’, J ϭ 7.7 Hz, 1 H, 9-H), 7.91 (d, J ϭ 9.5 Hz, 1 H, 12a-H), 7.93
(d, J ϭ 9.5 Hz, 1 H, 12b-H), 7.97 (‘‘t’’, J ϭ 7.5 Hz, 1 H, 2-H), 8.07
(‘‘d’’, J ϭ 7.5 Hz, 1 H, 1a-H), 8.08 (‘‘d’’, J ϭ 7.5 Hz, 1 H, 1b-H),
8.19 (‘‘d’’, J ϭ 9.4 Hz, 1 H, 5a-H), 8.23 (‘‘d’’, J ϭ 7.5 Hz, 2 H, 3-
H, 5b-H), 8.31 (‘‘d’’, J ϭ 9.4 Hz, 1 H, 4a-H), 8.33 (‘‘d’’, J ϭ 9.4 Hz,
1 H, 4b-H), 8.42 (‘‘d’’, J ϭ 7.7 Hz, 1 H, 7a-H), 8.55 (‘‘d’’, J ϭ
8.0 Hz, 1 H, 7b-H), 9.07 (d, J ϭ 9.5 Hz, 1 H, 11-H), 9.09 (‘‘d’’, J ϭ
7.7 Hz, 1 H, 10-H) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 23.8
(q, C-1Ј), 49.3 (t, C-3Јa), 49.5 (t, C-3Јb), 65.6 (t, C-2Јa), 66.0 (t, C-
2Јb), 119.9 (d, C-5Јa), 120.0 (d, C-5Јb), 122.1 (d, C-11Јa), 122.1 (d,
C-11Јb), 123.2 (d, C-10a), 123.2 (d, C-10b), 124.8 (d, C-1a), 124.9
(d, C-1b), 125.8Ϫ126.2 (10 d, C-2a/b, C-3a/b, C-5a/b, C-8a/b, C-9a/b),
126.9 (d, C-7a), 127.0 (d, C-7b), 127.4 (d, C-4a), 127.5 (d, C-4b),
128.0 (d, C-12a/b), 131.6 (2d, C-2Јa/b), 144 (s, C-6a/b) ppm. MS (EI):
m/z (%) ϭ 336 (58) [Mϩ], 318 (5), 291 (100), 276 (54), 265 (12), 252
(11). Because of hindered rotation of the C6/C4Ј bond, compound
9 shows two data sets in the NMR, therefore subscipts ‘‘a’’ and ‘‘b’’
in the NMR assignments refer to pairs of signals of the rotamers.
Singlets of minor intensity in the 13C NMR could not be listed.
Warning! Because of the mutagenicity of B[a]P (1) and its deriva-
tives, one must carefully avoid any contact of these substances with
the skin and must prevent accidental inhalation of powder or contami-
nated dust by use of appropriate protection methods.
All new compounds were pure according to their 1H NMR spectra;
because of the potential mutagenicity, elemental analyses were dis-
pensed with.
6-Iodobenzo[a]pyrene (2): A suspension of B[a]P (1, 400 mg,
1.59 mmol), NIS (421 mg, 1.60 mmol) and acid alumina (10 g) in
dry toluene (30 mL) was intensively stirred for 4 days. The alumina
was filtered off and washed with CH2Cl2 (150 mL). The combined
organic layers were extracted with Na2SO3 solution (50 mL), water
(50 mL) and brine (50 mL). After the solution had been dried with
MgSO4, the solvents were distilled off and recrystallisation from
petroleum ether (80/100) yielded 2 (480 mg, 1.27 mmol, 80%) as a
pale yellow powder. Rf ϭ 0.32 (silica, MTBE/petroleum ether,
1:29). IR (KBr): ν˜ ϭ 3046 cmϪ1 (w), 1250 (m), 899 (m), 836 (vs),
823 (s), 754 (s), 685 (m). 1H NMR (400 MHz, CDCl3): δ ϭ
7.82Ϫ7.87 (m, 2 H, 8-H, 9-H), 8.00 (dd, J ϭ 8.0, 7.5 Hz, 1 H, 2-
H), 8.00 (d, J ϭ 9.5 Hz, 1 H, 4-H), 8.14 (‘‘d’’, J ϭ 7.5 Hz, 1 H, 3-
H), 8.25 (‘‘d’’, J ϭ 8.0 Hz, 1 H, 1-H), 8.35 (d, J ϭ 9.0 Hz, 1 H, 12-
H), 8.54 (d, J ϭ 9.5 Hz, 1 H, 5-H), 8.83Ϫ8.85 (m, 1 H, 7-H),
9.00Ϫ9.02 (m, 1 H, 10-H), 9.05 (d, J ϭ 9.0 Hz, 1 H, 11-H) ppm.
13C NMR (100 MHz, CDCl3): δ ϭ 104.6 (s, C-6), 122.1 (d, C-11),
123.3 (d, C-10), 124.5 (s, C-12b), 124.6 (s, C-12c), 125.7 (d, C-3),
126.5 (2d, C-1, C-2), 126.7 (d, C-9), 127.9 (d, C-8), 128.1 (s, C-
10a), 128.4 (d, C-12), 128.8 (s, C-10b), 130.3 (d, C-4), 131.3 (s, C-
12a), 131.4 (s, C-3a), 132.8 (s, C-6a), 132.9 (s, C-5a), 133.6 (d, C-
5), 134.6 (d, C-7) ppm. MS (EI): m/z (%) ϭ 378 (100) [Mϩ], 251
(44), 250 (45), 224 (5), 125 (40).
4-(Benzo[a]pyren-6-yl)butan-2-one (4a): In a screw-cap vessel under
argon, a solution of iodide 2 (150 mg, 0.4 mmol), the alcohol 3a
(70 µL, 1.4 mmol), Pd(OAc)2 (10 mg, 0.04 mmol), LiCl (20 mg,
0.4 mmol) and NEt3 (200 µL, 1.4 mmol) in dry DMF (15 mL) were
heated to 120 °C for 14 h. After the mixture had cooled, toluene
(80 mL) was added and the solution was extracted tree times with
water (40 mL) and with brine (40 mL). Drying with MgSO4, evap-
oration of the solvent and flash chromatography (silica, MTBE/
petroleum ether, 1:2) yielded 4a (98 mg, 0.30 mmol, 76%) as a pale
yellow oil. Rf ϭ 0.43 (silica, MTBE/petroleum ether, 1:2). IR (KBr):
ν˜ ϭ 2930 cmϪ1 (w), 2866 (w), 1734 (s), 1495 (s), 1439 (s), 1176 (m),
826 (m). 1H NMR (400 MHz, CDCl3): δ ϭ 2.21 (s, 3 H, 1Ј-H),
2.95Ϫ2.99 (m, 2 H, 3Ј-H), 3.98Ϫ4.02 (m, 2 H, 4Ј-H), 7.78Ϫ7.83
(m, 2 H, 8-H, 9-H), 7.92 (d, J ϭ 9.3 Hz, 1 H, 12-H), 7.94 (‘‘t’’, J ϭ
7.5 Hz, 1 H, 2-H), 8.04 (dd, J ϭ 7.5, 1.0 Hz, 1 H, 1-H), 8.18 (dd,
J ϭ 7.5, 1.0 Hz, 1 H, 3-H), 8.20 (d, J ϭ 10.0 Hz, 1 H, 4-H), 8.22
(d, J ϭ 10.0 Hz, 1 H, 5-H), 8.45Ϫ8.47 (m, 1 H, 7-H), 8.99 (d, J ϭ
9.3 Hz, 1 H, 11-H), 9.06Ϫ9.09 (m, 1 H, 10-H) ppm. 13C NMR
(100 MHz, CDCl3): δ ϭ 22.2 (t, C-4Ј), 30.2 (q, C-1Ј), 44.8 (t, C-
3Ј), 122.2 (d, C-11), 123.9 (d, C-10), 123.9 (s, C-12c), 124.1 (d, C-
5), 124.6 (d, C-1), 124.9 (d, C-7), 125.6 (s, C-12b), 125.8 (d, C-3),
125.9 (s, C-5a), 125.9 (d, C-9), 126.2 (d, C-2), 126.6 (d, C-8), 126.7
(s, C-10b), 127.2 (d, C-4), 128.4 (s, C-10a), 128.5 (d, C-12), 129.6
(s, C-6a), 131.2 (s, C-3a), 131.6 (s, C-12a), 131.6 (s, C-6), 208.0 (s,
C-2Ј) ppm. MS (EI): m/z (%) ϭ 322 (12) [Mϩ], 278 (10), 265 (100),
251 (6), 250 (4), 43 (10).
5-(Benzo[a]pyren-6-yl)-1-(morpholin-4-yl)butane-1-thione (5a): The
ketone 4a (100 mg, 0.31 mmol) was heated to 140 °C with sulfur
(40 mg, 1.24 mmol) in dry morpholine for 6 h. After the mixture
had cooled, toluene (100 mL) was added and the layer was washed
twice with AcOH (10%, 40 mL), then with water (40 mL) and brine
(40 mL). Drying with MgSO4, evaporation of the solvent and chro-
matography (silica, MTBE/petroleum ether, 1:2) yielded 5a (52 mg,
0.12 mmol, 39%) and the by-product 12 (20 mg, 0.05 mmol, 15%)
as yellow oils. Rf ϭ 0.44. IR (KBr): ν˜ ϭ 3042 cmϪ1 (m), 2963 (s),
2857 (s), 1488 (s), 1462 (s), 1280 (s), 990 (m), 840 (m), 828 (m), 759
1
(m), 693 (w). H NMR (400 MHz, CDCl3): δ ϭ 2.36 (tt, J ϭ 8.2,
7.5 Hz, 2 H, 3Ј-H), 2.99 (t, J ϭ 7.5 Hz, 2 H, 2Ј-H), 3.33Ϫ3.41 (m,
4 H, CH2N), 3.70Ϫ3.73 (m, 2 H, CH2O), 3.90 (t, J ϭ 8.2 Hz, 2 H,
4Ј-H), 4.92Ϫ4.32 (m, 2 H, CH2O), 7.79Ϫ7.84 (m, 2 H, 8-H, 9-H),
7.95 (d, J ϭ 9.3 Hz, 1 H, 12-H), 7.96 (dd, J ϭ 7.5, 7.0 Hz, 1 H, 2-
H), 8.06 (‘‘d’’, J ϭ 7.0 Hz, 1 H, 1-H), 8.20 (‘‘d’’, J ϭ 7.5 Hz, 1 H,
3-H), 8.26 (d, J ϭ 9.0 Hz, 1 H, 4-H), 8.28 (d, J ϭ 9.0 Hz, 1 H, 5-
5-(Benzo[a]pyren-6-yl)pentan-2-one (4b): By use of the same pro-
cedure as described for 4a and by starting from the iodide 2
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FULL PAPER
H), 8.54Ϫ8.56 (m, 1 H, 7-H), 9.03 (d, J ϭ 9.0 Hz, 1 H, 11-H), By-Product 13: Rf ϭ 0.74. IR (KBr): ν˜ ϭ 3041 cmϪ1 (w), 2977 (w),
9.08Ϫ9.11 (m, 1 H, 10-H) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 2940 (w), 1709 (s), 1464 (m), 1413 (m), 1111 (m), 837 (s), 826 (m),
27.2 (t, C-4Ј), 30.1 (t, C-3Ј), 42.6 (t, C-2Ј), 49.8 (t, CH2N), 49.9 (t, 754 (s), 678 (m). 1H NMR (400 MHz, CDCl3): δ ϭ 1.10 (t, J ϭ
CH2O), 66.2 (t, CH2N), 66.5 (t, CH2O), 122.1 (d, C-11), 123.8 (s, 7.3 Hz, 3 H, 5Ј-H), 2.45 (d, J ϭ 7.3 Hz, 2 H, 4Ј-H), 2.95 (t, J ϭ
C-12c), 123.8 (d, C-10), 124.3 (d, C-5), 124.8 (d, C-7), 124.8 (d, C-
1), 125.6 (s, C-12b), 125.7 (d, C-9), 125.8 (d, C-3), 126.2 (d, C-2), 2 H, 8-H, 9-H), 7.93 (d, J ϭ 9.3 Hz, 1 H, 12-H), 7.94 (‘‘t’’, J ϭ
126.6 (d, C-8), 126.6 (s, C-5a), 127.2 (d, C-4), 127.5 (s, C-10b), 7.5 Hz, 1 H, 2-H), 8.04 (‘‘d’’, J ϭ 7.5 Hz, 1 H, 1-H), 8.18 (‘‘d’’,
8.2 Hz, 1 H, 2Ј-H), 4.02 (t, J ϭ 8.3 Hz, 1 H, 1Ј-H), 7.80Ϫ7.82 (m,
128.2 (d, C-12), 128.3 (s, C-10a), 129.8 (s, C-6a), 131.1 (s, C-3a), J ϭ 7.5 Hz, 1 H, 3-H), 8.22 (d, J ϭ 9.0 Hz, 1 H, 4-H), 8.24 (d, J ϭ
131.6 (s, C-12a), 132.0 (s, C-6), 203.2 (s, C-1Ј) ppm. MS (EI): m/z 9.0 Hz, 1 H, 5-H), 8.46Ϫ8.48 (m, 1 H, 7-H), 9.01 (d, J ϭ 9.5 Hz,
(%) ϭ 423 (35) [Mϩ], 278 (100), 265 (18), 250 (4).
1 H, 11-H), 9.07Ϫ9.09 (m, 1 H, 10-H) ppm. 13C NMR (100 MHz,
By-Product 12: Rf ϭ 0.88. IR (KBr): ν˜ ϭ 3041 cmϪ1 (w), 2926 (w), CDCl3): δ ϭ 17.9 (q, C-5Ј), 22.3 (t, C-1Ј), 36.2 (t, C-4Ј), 43.3 (t, C-
2858 (w), 1616 (m), 1584 (m), 1464 (m), 1432 (m), 1114 (s), 1063 2Ј), 122.1 (d, C-11), 123.8 (d, C-10), 123.8 (s, C-12c), 124.0 (d, C-
(m), 839 (s), 826 (m), 758 (m), 634 (m). 1H NMR (400 MHz, 5), 124.5 (d, C-7), 124.8 (d, C-1), 125.5 (s, C-12b), 125.7 (d, C-9)
CDCl3): δ ϭ 3.22 (ddd, J ϭ 9.5, 6.5, 2.4 Hz, 4 H, CH2N), 3.85 125.7 (d, C-3), 126.2 (d, C-2), 126.4 (d, C-8), 126.6 (s, C-5a), 127.1
(ddd, J ϭ 9.5, 6.5, 2.4 Hz, 4 H, CH2O), 6.29 (d, J ϭ 3.5 Hz, 1 H, (d, C-4), 127.1 (s, C-10b), 128.2 (s, C-10a), 128.3 (d, C-12), 129.5
3Ј-H), 6.87 (d, J ϭ 3.5 Hz, 1 H, 4Ј-H), 7.63Ϫ7.67 (m, 1 H, 8-H),
(s, C-6a), 131.2 (s, C-3a), 131.6 (s, C-12a), 131.8 (s, C-6), 210.7 (s,
7.73Ϫ7.75 (m, 1 H, 9-H), 7.79 (d, J ϭ 9.5 Hz, 1 H, 12-H), 7.91 C-3Ј) ppm. MS (EI): m/z (%) ϭ 336 (74) [Mϩ], 276 (12), 265 (100),
(‘‘t’’, J ϭ 7.9 Hz, 1 H, 2-H), 7.98 (d, J ϭ 9.0 Hz, 1 H, 5-H), 8.00 252 (6), 250 (5), 239 (5).
(‘‘d’’, J ϭ 6.5 Hz, 1 H, 7-H), 8.17 (dd, J ϭ 7.9 Hz, 1.0, 1 H, 1-H), By-product 14: Rf ϭ 0.58. IR (KBr): ν˜ ϭ 3045 cmϪ1 (w), 3045 (w),
8.23 (dd, J ϭ 7.9 Hz, 1.0, 1 H, 3-H), 8.28 (d, J ϭ 9.0 Hz, 1 H, 12-
H), 9.02 (d, J ϭ 9.0 Hz, 2 H, 10-H, 11-H) ppm. 13C NMR
(100 MHz, CDCl3): δ ϭ 50.5 (t, CH2N), 65.5 (t, CH2O), 104 (d,
2926 (w), 1713 (vs), 1678 (s), 1459 (w), 1416 (w), 1123 (m), 839 (s),
827 (m), 760 (s), 691 (m). H NMR (400 MHz, CDCl3): δ ϭ 1.86
(s, 3 H, 1Ј-H), 2.97 (ddd, J ϭ 18.1 Hz, 11.8, 6.5, 2 H, 3Ј-H), 6.60
1
C-3Ј), 121.1 (d, C-11), 121.8 (d, C-10), 122.4 (s, C-12c), 124.1 (d, (ddd, J ϭ 18.8 Hz, 11.4, 11.8, 1 H, 4Ј-H), 7.35 (d, J ϭ 11.4 Hz, 1
C-6), 124.1 (d, C-7), 124.4 (s, C-12b), 124.8 (d, C-1), 124.9 (d, C- H, 5Ј-H), 7.77 (‘‘t’’, 1 H, 8-H), 7.84 (‘‘t’’, 1 H, 9-H), 7.90 (d, J ϭ
9), 125.2 (d, C-5Ј), 125.2 (d, C-2), 125.2 (d, C-8), 125.7 (d, C-5), 9.3 Hz, 1 H, 12-H), 7.97 (‘‘t’’, J ϭ 7.5 Hz, 1 H, 2-H), 8.07 (‘‘d’’,
126.5 (s, C-10b), 126.7 (d, C-3), 126.8 (s, C-10a), 127.0 (d, C-12), J ϭ 7.5 Hz, 1 H, 1-H), 8.11 (d, J ϭ 9.0 Hz, 1 H, 5-H), 8.23 (‘‘d’’,
127.0 (d, C-4), 127.6 (d, C-4Ј), 129.4 (s, C-5a), 130.2 (s, C-12a), J ϭ 7.5 Hz, 1 H, 3-H), 8.31 (d, J ϭ 9.0 Hz, 1 H, 4-H), 8.42 (‘‘d’’,
130.4 (s, C-3a), 131.2 (s, C-6a), 159.1 (s, C-2Ј) ppm. MS (EI): m/z 1 H, 7-H), 9.06 (d, J ϭ 9.3 Hz, 1 H, 11-H), 9.09 (‘‘d’’, 1 H, 10-H)
(%) ϭ 420 (100) [Mϩ], 402 (18), 333 (6), 265 (100), 251 (4), 250 (6), ppm. 13C NMR (100 MHz, CDCl3): 30.0 (q, C-1Ј), 43.6 (t, C-3Ј),
239 (3).
122.1 (d, C-11), 123.3 (d, C-10), 123.5 (s, C-12c), 125.1 (d, C-1),
125.5 (s, C-12b), 125.9 (d, C-3), 125.9 (d, C-9), 126.0 (d, C-5), 126.2
(d, C-8), 126.3 (d, C-2), 126.6 (d, C-7), 127.1 (s, C-5a), 127.1 (s, C-
10b), 127.6 (d, C-4), 128.0 (s, C-10a), 128.2 (d, C-12), 128.5 (d, C-
4Ј), 129.3 (d, C-5Ј), 129.5 (s, C-6), 129.6 (s, C-6a), 131.3 (s, C-3a),
131.6 (s, C-12a), 206.4 (s, C-2Ј) ppm. MS (EI): m/z (%) ϭ 334 (11)
[Mϩ], 289 (17), 276 (28), 149 (100), 43 (48).
5-(Benzo[a]pyren-6-yl)-1-(morpholin-4-yl)pentane-1-thione (5b):
A
solution of the ketone 4b (370 mg, 1.1 mmol) and sulfur (100 mg,
3.3 mmol) in dry morpholine (50 mL) was heated under argon in
a screw-cap vessel at 140 °C for 6 h. After the mixture had cooled,
toluene (200 mL) was added and the layer was washed four times
with HCl (10%, 50 mL) and then with water (50 mL) and brine
(50 mL). The organic layer was dried with MgSO4, the solvent was
distilled off and the residue was fractionated by flash chromatogra-
3-(Benzo[a]pyren-6-yl)propanoic Acid (6): NaOH (585 mg) was dis-
solved with stirring in water (3.3 mL), and bromine (184 µL) was
phy (silica, MTBE/petroleum ether, 1:1). Yield: 90 mg (0.21 mmol, added dropwise at 0 °C. Two thirds of this freshly prepared hypo-
19%) of 5b, 13 mg (0.04 mmol, 4%) of the starting material isomer
13 and 15 mg (0.05 mmol, 4%) of the olefin 14 as yellow oils. Rf ϭ
0.35. IR (KBr): ν˜ ϭ 3041 cmϪ1 (m), 2961 (s), 2857 (s), 1637 (m),
bromide solution were added dropwise at room temperature to a
solution of methyl ketone 4a (200 mg, 0.57 mmol), and after the
mixture had been stirred for 3 h the rest of the hypobromide solu-
1463 (s), 1431 (s), 1273 (m), 1114 (s), 961 (m), 839 (s), 826 (m), 758 tion (stored at 0 °C) was added and stirring was continued for a
(s), 693 (m). 1H NMR (400 MHz, CDCl3): δ ϭ 1.99Ϫ2.05 (m, 4
further 3 h. The reaction mixer was poured into toluene (100 mL)
H, 3Ј-H, 4Ј-H), 2.92 (t, J ϭ 7.3 Hz, 2 H, 2Ј-H), 3.50 (ddd, J ϭ 9.2, and neutralized with HCl. The organic layer was separated in a
7.5, 1.0 Hz, 2 H, CH2N), 3.57 (ddd, J ϭ 9.2 Hz, 7.5, 1.0 Hz, 2 H, dropping funnel and washed with water (30 mL) and brine
CH2N), 3.71 (ddd, J ϭ 9.2, 7.5, 2.0 Hz, 2 H, CH2O), 3.82 (t, J ϭ (30 mL). After the solution had been dried with MgSO4, the sol-
7.5 Hz, 2 H, 5Ј-H), 4.30 (ddd, J ϭ 9.2, 7.5, 2.0 Hz, 2 H, CH2O), vents were distilled off and the crude acid was purified by chroma-
7.81Ϫ7.85 (m, 2 H, 8-H, 9-H), 7.96 (d, J ϭ 9.6 Hz, 1 H, 12-H), tography (silica, MTBE/PE). Yield: 103 mg (0.32 mmol, 56%) of 6,
7.96 (‘‘t’’, J ϭ 7.5 Hz, 1 H, 2-H), 8.07 (dd, J ϭ 7.5, 1.0 Hz, 1 H, which was recrystallized from heptane for an analytical sample.
1-H), 8.21 (dd, J ϭ 7.5, 1.0 Hz, 1 H, 3-H), 8.27 (d, J ϭ 9.5 Hz, 1
H, 4-H), 8.30 (d, J ϭ 9.5 Hz, 1 H, 5-H), 8.54Ϫ8.57 (m, 1 H, 7-H), (w), 2915 (w), 1708 (s), 1464 (m), 1164 (m), 836 (m), 834 (m), 755
9.03 (d, J ϭ 9.5 Hz, 1 H, 11-H), 9.10Ϫ9.12 (m, 1 H, 10-H) ppm. (s), 692 (m). 1H NMR (400 MHz, [D6]DMSO): δ ϭ 2.73 (t, J ϭ
Rf ϭ 0.35 (silica, MTBE/PE). IR (KBr): ν˜ ϭ 3037 cmϪ1 (w), 2974
13C NMR (100 MHz, CDCl3): δ ϭ 27.1 (t, C-5Ј), 28.6 (t, C-4Ј), 8.3 Hz, 2 H, 2Ј-H), 4.02 (t, J ϭ 8.3 Hz, 2 H, 3Ј-H), 7.87Ϫ7.92 (m,
30.0 (t, C-3Ј), 42.50 (t, C-2Ј), 49.1 (t, CH2N), 49.2 (t, CH2O), 65.4 2 H, 8-H, 9-H), 8.03 (‘‘t’’, J ϭ 7.5 Hz, 1 H, 2-H), 8.07 (d, J ϭ
(t, CH2N), 65.6 (t, CH2O), 122.3 (d, C-11), 122.8 (d, C-10), 123.0 9.3 Hz, 1 H, 12-H), 8.18 (‘‘d’’, J ϭ 7.5 Hz, 1 H, 1-H), 8.31 (‘‘d’’,
(s, C-12c), 123.5 (d, C-5), 123.7 (d, C-1), 123.7 (d, C-7), 124.7 (s, J ϭ 7.5 Hz, 1 H, 3-H), 8.37 (d, J ϭ 9.0 Hz, 1 H, 4-H), 8.38 (d, J ϭ
C-12b), 124.7 (d, C-9), 124.8 (d, C-3), 125.2 (d, C-2), 125.3 (d, C-
8), 125.6 (s, C-5a), 126.1 (d, C-4), 126.3 (s, C-10b), 127.2 (d, C-12),
127.4 (s, C-10a), 128.9 (s, C-6a), 130.3 (s, C-3a), 130.7 (s, C-12a),
132.0 (s, C-6), 202.6 (s, C-1Ј) ppm. MS (EI): m/z (%) ϭ 437 (44)
9.0 Hz, 1 H, 5-H), 8.61 (‘‘d’’, J ϭ 7.5 Hz, 1 H, 7-H), 9.19 (d, J ϭ
9.3 Hz, 1 H, 11-H), 9.24 (‘‘d’’, J ϭ 9.0 Hz, 1 H, 10-H), 12.35 (s, 1
H, COOH) ppm. 13C NMR (100 MHz, [D6]DMSO): δ ϭ 23.2 (t,
C-3Ј), 35.3 (t, C-2Ј), 122.3 (d, C-11), 122.8 (s, C-12c), 123.9 (d, C-
[Mϩ], 421 (6), 404 (21), 292 (23), 277 (15), 265 (100), 252 (11), 10), 124.5 (d, C-5), 124.5 (s, C-12b), 124.6 (d, C-7), 124.8 (d, C-1),
172 (63).
125.7 (d, C-3), 126.0 (d, C-9), 126.1 (s, C-5a), 126.4 (d, C-2), 126.6
3170
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 3167Ϫ3172

Synthesis of Benzo[a]pyren-6-yl-Substituted Carboxylic Acids
FULL PAPER
(s, C-10b), 126.8 (d, C-8), 127.2 (d, C-4), 127.7 (s, C-10a), 128.2 (d, then filtered off and washed with a little water and MTBE. Yield:
C-12), 129.1 (s, C-6a), 130.6 (s, C-3a), 131.0 (s, C-12a), 131.6 (s, C- 64 mg (0.13 mmol, 71%) of the dibromo compound 10. IR (KBr):
6), 173.7 (s, C-1Ј) ppm. MS (EI): m/z (%) ϭ 324 (47) [Mϩ], 276 ν˜ ϭ 3073 cmϪ1 (w), 2928 (w), 2892 (w), 1715 (vs), 1593 (w), 1479
(13), 265 (100), 251 (3), 250 (5), 239 (6).
(m), 900 (s), 813 (s), 752 (s), 652 (m). 1H NMR (400 MHz, CDCl3):
δ ϭ 2.14Ϫ2.21 (m, 2 H, 4Ј-H), 2.20 (s, 3 H, 1Ј-H), 2.69 (‘‘t’’, J ϭ
6.8 Hz, 2 H, 3Ј-H), 3.73Ϫ3.77 (m, 2 H, 5Ј-H), 7.85Ϫ7.90 (m, 2 H,
8-H, 9-H), 8.27 (d, J ϭ 9.8 Hz, 1 H, 5-H), 8.46 (s, 1 H, 2-H), 8.47
(d, J ϭ 9.8 Hz, 1 H, 4-H), 8.57 (d, J ϭ 9.5 Hz, 1 H, 12-H),
8.62Ϫ8.65 (m, 1 H, 7-H), 9.08Ϫ9.10 (m, 1 H, 10-H), 9.13 (d, J ϭ
9.5 Hz, 1 H, 11-H) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 25.1
(t, C-4Ј), 27.8 (t, C-5Ј), 30.2 (q, C-1Ј), 43.1 (t, C-3Ј), 118.9 (s, C-3),
119.9 (s, C-1), 122.7 (s, C-12c), 123.7 (d, C-11), 123.8 (d, C-10),
125.1 (d, C-7), 125.5 (d, C-12), 126.0 (d, C-4), 126.3 (d, C-5), 126.4
(d, C-9), 126.8 (s, C-12b), 126.9 (s, C-10b), 127.1 (d, C-8), 127.5 (s,
C-6a), 128.5 (s, C-5a), 129.3 (s, C-10a), 129.4 (s, C-12a), 130.4 (s,
C-3a), 133.5 (d, C-2), 134.7 (s, C-6), 208.4 (s, C-2Ј) ppm. MS (EI):
m/z (%) ϭ 495 (65) [Mϩ], 436 (20), 423 (100), 344 (8), 263 (92), 251
(4), 43 (25).
4-(Benzo[a]pyren-6-yl)butanoic Acid (7): Water (1 mL) and KOH
(1.2 g, 23 mmol) were added to a well degassed solution of 5a
(400 mg, 0.91 mmol) in 2-methoxyethylene glycol (50 mL) and the
mixture was heated at reflux under argon for 6 h. Toluene (200 mL)
was added, and the organic layer was extracted first with half con-
centrated Na2CO3 solution (50 mL) and then twice with concen-
trated Na2CO3 solution (50 mL). The combined aqueous layers
were acidified to pH 2 with HCl and then extracted three times
with toluene (50 mL). The toluene phases were washed with brine
(50 mL) and dried with MgSO4, and the solvents were evaporated
to dryness. Chromatography (silica, ethyl acetate/petroleum ether,
1:3) yielded the acid 7 (120 mg, 0.35 mmol, 39%) as a yellow/grey
powder. Rf ϭ 0.23. IR (KBr): ν˜ ϭ 3038 cmϪ1 (m), 2965 (m) 1698
(s), 1407 (m), 837 (m), 826 (m), 757 (s), 692 (m). 1H NMR
(400 MHz, [D6]DMSO): δ ϭ 2.05 (tt, J ϭ 8.2 Hz, 7.0, 2 H 3Ј-H),
2.58 (t, J ϭ 7.0 Hz, 2 H, 2Ј-H), 3.78 (t, J ϭ 8.2 Hz, 2 H, 4Ј-H),
7.90 (‘‘dd’’, J ϭ 6.5, 3.0 Hz, 2 H, 8-H, 9-H), 8.04 (‘‘t’’, J ϭ 7.4 Hz,
1 H, 2-H), 8.08 (d, J ϭ 9.3 Hz, 1 H, 12-H), 8.19 (‘‘d’’, J ϭ 7.4 Hz,
1 H, 1-H), 8.33 (‘‘d’’, J ϭ 7.4 Hz, 1 H, 3-H), 8.39 (d, J ϭ 9.5 Hz,
1 H, 4-H), 8.46 (d, J ϭ 9.5 Hz, 1 H, 5-H), 8.72 (‘‘dd’’, J ϭ 6.5,
3.0 Hz, 1 H, 7-H), 9.23 (d, J ϭ 9.3 Hz, 1 H, 11-H), 9.27 (‘‘dd’’, J ϭ
6.5, 3.0 Hz, 1 H, 10-H), 12.17 (s, 1 H, COOH) ppm. 13C NMR
(100 MHz, [D6]DMSO): δ ϭ 26.3 (t, C-3Ј), 27.1 (t, C-4Ј), 33.5 (t,
C-2Ј), 122.4 (d, C-11), 122.9 (s, C-12c), 123.8 (d, C-10), 124.4 (d,
C-5), 124.6 (s, C-12b), 124.7 (d, C-7), 124.9 (d, C-1), 125.6 (d, C-
3), 125.9 (s, C-5a), 126.0 (d, C-9), 126.3 (d, C-2), 126.6 (s, C-10b),
126.6 (d, C-8), 127.0 (d, C-4), 127.7 (s, C-10a), 127.9 (d, C-12),
129.4 (s, C-6a), 130.7 (s, C-3a), 131.1 (s, C-12a), 133.0 (s, C-6),
174.5 (s, C-1Ј) ppm. MS (EI): m/z (%) ϭ 338 (38) [Mϩ], 276 (9),
265 (100), 251 (3), 250 (3), 239 (4).
tert-Butyl 4-(Benzo[a]pyren-6-yl)-2-methylbutanoate (11): The ke-
tone 4b (140 mg), potassium tert-butoxide (470 mg, 4.2 mmol) and
iodine (210 mg, 0.84 mmol) were dissolved in dry tert-butyl alcohol
(80 mL) in a screw-cap vessel, and heated to 90 °C under argon for
2 h. The solvent was distilled off and the residue was redissolved in
toluene (100 mL). After having been washed with Na2SO3 solution
(40 mL), water (50 mL) and brine the solution was dried with
MgSO4. Evaporation of the solvent and chromatography (silica,
ethyl acetate/petroleum ether, 1:2) yielded the ester 11 (65 mg,
0.16 mmol). Rf ϭ 0.35. IR (KBr): ν˜ ϭ 3040 cmϪ1 (w), 2974 (w),
2941 (w), 1715 (vs), 1515 (w), 1491 (w), 1228 (w), 837 (m), 824v
1
(m), 756 (s), 692 (m). H NMR (400 MHz, CDCl3): δ ϭ 1.31 (d,
J ϭ 7.0 Hz, 3 H, Me) 1.60 (s, 9 H, tBu), 1.92Ϫ2.01 (m, 1 H, 3aЈ-
H), 2.17Ϫ2.27 (m, 1 H, 3bЈ-H), 2.68Ϫ2.72 (m, 1 H, 2Ј-H),
3.69Ϫ3.82 (m, 2 H, 4Ј-H), 7.81Ϫ7.83 (m, 2 H, 8-H, 9-H), 7.94 (dd,
J ϭ 7.9, 7.5 Hz, 1 H, 2-H), 7.95 (d, J ϭ 9.3 Hz, 1 H, 12-H), 8.06
(dd, J ϭ 7.5, 1.0 Hz, 1 H, 1-H), 8.19 (d, J ϭ 7.9, 1.0 Hz, 1 H, 3-
H), 8.25 (d, J ϭ 9.3 Hz, 1 H, 4-H), 8.30 (d, J ϭ 9.3 Hz, 1 H, 5-H),
8.56Ϫ8.59 (m, 1 H, 7-H), 9.03 (d, J ϭ 9.3 Hz, 1 H, 11-H),
9.09Ϫ9.10 (m, 1 H, 10-H) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ
17.8 (q, Me), 26.5 (t, C-4Ј), 28.4 (q, tBu), 35.3 (t, C-3Ј), 41.4 (t, C-
2Ј), 80.5 (s, tBu), 122.3 (d, C-11), 123.8 (d, C-10), 124.0 (s, C-12c),
124.5 (d, C-5), 124.7 (d, C-1), 125.0 (d, C-7), 125.6 (s, C-12b), 125.7
(2d, C-3,C-9), 126.1 (d, C-8), 126.4 (d, C-2), 126.6 (s, C-5a), 127.0
(d, C-4), 127.2 (s, C-10b), 128.2 (d, C-12), 128.4 (s, C-10a), 129.9
(s, C-6a), 131.4 (s, C-3a), 131.7 (s, C-12a), 133.0 (s, C-6), 176.1 (s,
C-1Ј) ppm. MS (EI): m/z (%) ϭ 307 (2), 286 (36), 265 (10), 252
(100), 250 (28), 125 (18).
5-(Benzo[a]pyren-6-yl)pentanoic Acid (8): The acid
8 (55 mg,
0.16 mmol, 58%) was obtained by use of the same procedure as
described for 7, starting from compound 5b (120 mg, 0.27 mmol)
with KOH (350 mg, 6.1 mmol) in 2-methoxyethylene glycol
(30 mL). Rf ϭ 0.20 (silica, ethyl acetate/petroleum ether, 1:1). IR
(KBr): ν˜ ϭ 3452 cmϪ1 (s), 3036 (m), 2927 (m) 1707 (vs), 1407 (m),
837 (s), 824 (m), 755 (s), 691 (m). 1H NMR (400 MHz, (CD3)2CO]:
δ ϭ 1.98Ϫ2.00 (m, 4 H, 4Ј-H, 3Ј-H), 2.47 (t, J ϭ 6.5 Hz, 2 H, 2Ј-
H), 3.85 (t, J ϭ 7.3 Hz, 2 H, 4Ј-H), 7.87 (‘‘dd’’, J ϭ 7.2 Hz, 3.0, 2
H, 8-H, 9-H), 8.00 (‘‘t’’, J ϭ 7.5 Hz, 1 H, 2-H), 8.04 (d, J ϭ 9.5 Hz,
1 H, 12-H), 8.15 (‘‘d’’, J ϭ 7.5 Hz, 1 H, 1-H), 8.28 (‘‘d’’, J ϭ
7.5 Hz, 1 H, 3-H), 8.35 (d, J ϭ 9.3 Hz, 1 H, 4-H), 8.43 (d, J ϭ
9.3 Hz, 1 H, 5-H), 8.69 (‘‘dd’’, J ϭ 7.2 Hz, 3.0, 1 H, 7-H), 9.18 (d,
J ϭ 9.0 Hz, 1 H, 11-H), 9.23 (‘‘dd’’, J ϭ 7.2 Hz, 3.0, 1 H, 10-H),
10.50 (s, 1 H, COOH) ppm. 13C NMR (100 MHz, (CD3)2CO]: δ ϭ
26.2 (t, C-3Ј), 28.7 (t, C-5Ј), 31.8 (t, C-4Ј), 34.2 (t, C-2Ј), 123.3 (d,
C-11), 124.7 (s, C-12c), 124.7 (d, C-10), 125.6 (d, C-5), 125.7 (d, C-
1), 126.1 (d, C-7), 126.4 (s, C-12b), 126.6 (d, C-3), 126.8 (d, C-9),
127.3 (d, C-2), 127.4 (s, C-5a), 127.4 (d, C-8), 128.0 (s, C-10b),
128.0 (d, C-4), 129.0 (d, C-12), 129.4 (s, C-10a), 130.9 (s, C-6a),
132.4 (s, C-3a), 132.8 (s, C-12a), 134.6 (s, C-6), 174.7 (s, C-1Ј) ppm.
MS (EI): m/z (%) ϭ 352 (38) [Mϩ], 323 (Ͻ2), 289 (Ͻ2), 265 (100),
252 (3), 239 (4).
4-(Pyren-1-yl)pentan-2-one (16): The ketone 16 (180 mg,
0.63 mmol, 63%) was obtained by the same procedure as described
for 4, starting from the iodide 15 (330 mg, 1.0 mmol). Rf ϭ 0.33
(silica, MTBE/petroleum ether, 1:2). IR (KBr): ν˜ ϭ 2948 cmϪ1 (m),
2886 (m), 1711 (vs), 1601 (m), 1159 (m), 840 (m), 763 (m), 708 (m).
1H NMR (400 MHz, CDCl3): δ ϭ 2.11Ϫ2.18 (m, 2 H, 4Ј-H), 2.12
(s, 3 H, 1Ј-H), 2.54 (t, J ϭ 7.2 Hz, 2 H, 3Ј-H), 3.35 (t, J ϭ 7.7 Hz,
2 H, 5Ј-H), 7.83 (d, J ϭ 7.8 Hz, 1 H, 2-H), 7.98 (dd, J ϭ 7.8 Hz,
7.5, 1 H, 7-H), 8.02 (2d, J ϭ 9.0 Hz, 2 H, 4-H, 5-H), 8.10 (d, J ϭ
7.8 Hz, 1 H, 3-H), 8.11 (d, J ϭ 9.3 Hz, 1 H, 9-H), 8.15 (dd, J ϭ
7.8, 1.1 Hz, 1 H, 8-H), 8.16 (dd, J ϭ 7.5, 1.1 Hz, 1 H, 6-H), 8.30
(d, J ϭ 9.3 Hz, 1 H, 10-H) ppm. 13C NMR (100 MHz, CDCl3):
δ ϭ 25.7 (t, C-4Ј), 30.2 (q, C-1Ј), 32.8 (t, C-5Ј), 43.2 (t, C-3Ј), 123.6
5-(1,3-Dibromobenzo[a]pyren-6-yl)pentan-2-one (10): Ketone 4b
(60 mg, 0.18 mmol) in dry THF (8 mL) and dry dioxane (8 mL)
was added at 0 °C to a stirred solution of KOH (100 mg, 1.8 mmol) (d, C-10), 125.0 (2d, C-6,C-8), 125.1 (d, C-3), 125.2 (s, C-10b),
and bromine (280 µL, 0.54 mmol) in water (0.5 mL). The solution 125.3 (s, C-10c), 126.0 (d, C-7), 126.9 (d C-5/C-4), 127.5 (d, C-2),
was stirred at room temperature for 1 h and the precipitate was 127.6 (d, C-9), 127.7 (d, C-5/C-4), 129.0 (s, C-10a), 130.2 (s, C-3a),
Eur. J. Org. Chem. 2003, 3167Ϫ3172
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G. Dyker, D. Kadzimirsz
FULL PAPER
131.1 (s, C-8a), 131.6 (s, C-5a) 136.1 (s, C-1), 208.8 (s, C-2Ј) ppm.
MS (EI): m/z (%) ϭ286 (61) [Mϩ], 228 (74), 215 (100), 202 (7), 43
(43). C21H18O (286.14 g/mol)·1.5 H2O: calcd. C 86.98, H 6.40
found C 86.95, H 6.12.
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4-(Pyren-6-yl)butanoic Acid (7): The acid 17 (64 mg, 0.22 mmol,
79%) was obtained by the same procedure as described for 6, start-
ing from the ketone 16 (80 mg, 0.20 mmol). Rf ϭ 0.28 (silica,
MTBE/petroleum ether, 1:1). IR (KBr): ν˜ ϭ 2929 cmϪ1 (w), 1607
(m), 1451 (s), 1073 (m,) 988 (m), 878 (w), 834 (w). 1H NMR
(400 MHz, [D6]DMSO): δ ϭ 1.97Ϫ2.04 (m, 2 H, 3Ј-H), 2.38 (t,
J ϭ 7.3 Hz, 2 H, 2Ј-H), 3.34 (dd, J ϭ 8.7, 6.9 Hz, 2 H, 4Ј-H), 7.93
(d, J ϭ 7.8 Hz, 1 H, 2-H), 8.05 (dd, J ϭ 7.8, 7.5 Hz, 1 H, 7-H),
8.12 (2d, J ϭ 8.9 Hz, 2 H, 4-H, 5-H), 8.20 (d, J ϭ 9.4 Hz, 1 H, 9-
H), 8.22 (d, J ϭ 7.8 Hz, 1 H, 3-H), 8.24 (dd, J ϭ 7.5, 1.3 Hz, 2 H,
8-H), 8.27 (dd, J ϭ 7.8, 1.3 Hz, 2 H, 6-H), 8.39 (d, J ϭ 9.4 Hz, 1
H, 10-H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ ϭ 26.8 (t, C-
3Ј), 31.9 (q, C-2Ј), 33.3 (t, C-4Ј), 123.4 (d, C-10), 124.1 (s, C-10b),
124.2 (s, C-10c), 124.7 (d, C-3), 124.9 (2d, C-6,C-8), 126.1 (d, C-
7), 126.5 (d, C-4/C-5), 127.2 (d, C-2), 127.4 (d, C-9), 127.4 (d, C-
5/C-4), 128.1 (s, C-10a), 129.3 (s, C-3a), 130.4 (s, C-8a), 130.8 (s,
C-5a), 136.3 (s, C-1), 174.3 (s, C-1Ј).
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Financial support by the Fonds der Chemischen Industrie is grate-
fully acknowledged. We thank R. Nießner and D. Knopp from the
Institute of Hydrochemistry of the TU Munich for helpful dis-
cussions and support.
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Received April 4, 2003
3172
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2003, 3167Ϫ3172