A convenient synthesis of 2-naphthylcyclopentanones and 2-naphthylcyclohexanones from 1-naphthylcycloalkenes

Article abstract of DOI:10.1055/s-2005-865298

The oxidation of naphthylcycloalkenes with hydrogen peroxide or MCPBA followed by acid catalyzed rearrangement of diol (epoxide), afforded a series of naphthylcycloalkanones in a very simple manner. The conditions allow preparation of naphthylcycloalkanones on a multigram scale. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-865298

PAPER
1625
A Convenient Synthesis of 2-Naphthylcyclopentanones and 2-Naphthylcyclo-
hexanones from 1-Naphthylcycloalkenes
S
ynthesis of 2-Naphthy
a
lcycloalka
c
nones iej Góra,*a Michał K. Łuczyński,b Janusz J. Sepioła
a
Department of Organic Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland
Fax +48(12)6340515; E-mail: mgora@chemia.uj.edu.pl
b
Department of Chemistry, University of Warmia and Mazury in Olsztyn, Plac Lodzki 4, 10-957 Olsztyn, Poland
Received 20 January 2005; revised 31 January 2005
In all cases naphthylcycloalkenes were obtained by a two-
step procedure involving Grignard reaction of appropriate
naphthylmagnesium bromides with cycloalkanones and
dehydration of crude alcohols 2a–l by heating with formic
acid (Scheme 1). Conversion of 1 to the intermediate al-
cohols 2 was carried out in diethyl ether or THF, depend-
ing on the solubility of 1. Yields and methods of isolation
naphthylcycloalkenes 3 are described in Table 1.
Abstract: The oxidation of naphthylcycloalkenes with hydrogen
peroxide or MCPBA followed by acid catalyzed rearrangement of
diol (epoxide), afforded a series of naphthylcycloalkanones in a
very simple manner. The conditions allow preparation of naphthyl-
cycloalkanones on a multigram scale.
Key words: ketones, epoxidations, rearrangements, polycycles,
alkenes
(CH2)n
A number of methods have been reported for the synthesis
of 2-arylcycloalkanones including: reaction of arylmag-
nesium halides or aryllithiums with chlorocycloal-
kanones,1 diol and epoxide rearrangements,2 radical
ketone arylation,3 and oxidation of arylcycloalkanols.4
Other synthetic methods employing enamines,5 aryl-bis-
muth reagents,6 silyl enol ethers,7 1-nitrocycloalkenes,8
electrochemical9 and ring resizing10 reactions have also
been described. The most straightforward method in-
volves palladium-catalyzed coupling of aryl halides with
appropriate ketones.11
Br
OH
R1
i, ii
R3
R1
R3
R2
R2
1a–l
2a–l
(CH2)n
iii
R3
R1
R1, R2, R3 = H, CH3, OCH3
n = 1, 2
R2
3a–l
Recently, we reported a new aromatic rearrangement
leading to cycloalkaphenanthrenes having significant bio-
logical activity.12 Efficient synthesis of these polycyclic
aromatic hydrocarbons (PAHs) for investigations of the
mechanism of PAH related carcinogenesis still remains a
challenging problem. We needed a few grams each of the
2-naphthylcycloalkanones with varied substitutions in the
aryl rings. Surprisingly, reports on easily applicable syn-
thesis of naphthyl- and substituted naphthylcycloal-
kanones are rare. Among them, the approach involving
oxidation of appropriate cycloalkene to the epoxide, fol-
lowed by its acid-catalyzed rearrangement seemed to be
the most promising. This method is operationally simple
and the required starting materials are readily available
via classical Grignard reaction. In this paper, we describe
a multigram scale procedure for the preparation of the var-
ious substituted naphthylcycloalkanones.
Scheme 1 i) Mg/Et2O (THF); ii) cyclopentanone or cyclohexanone;
iii) 85% aq HCO2H, 100 °C
Initially we focused on hydrogen peroxide/formic acid as
the oxidizing agent. First, 1-cyclopent-1-en-1-ylnaphtha-
lene (3a) was chosen as a model for oxidation. After sev-
eral trials we found that the best results were achieved
when the H2O2/HCO2H mixture was added dropwise to a
well-stirred solution of 1 in acetone. We have applied
these conditions for converting different unsubstituted
naphthylcycloakenes to the corresponding ketones 4.
However, for most of the substituted naphthylcycloalk-
enes this oxidation procedure gave only 10–20% yield of
the target naphthylcycloalkanones. This forced us to use a
cold, ethyl acetate solution of MCPBA in the alkene oxi-
dation step, which after the rearrangement led to the re-
quired substituted naphthylcycloalkanones in satisfactory
yields (Scheme 2). We have noticed that the use of a chlo-
roform solution of MCPBA or perbenzoic acid in the case
of methoxy substituted naphthylcycloalkenes led mostly
to the products of aromatic ring oxidation.
Our synthetic plan was similar to that reported for several
simple phenyl derivatives,2 but the experimental condi-
tions were different due to higher reactivity of naphtha-
lene rings.
We have also compared the efficiency of two different re-
arrangement agents in the formation of naphthylcycloal-
kanones. The well-known method described by Ziffer et
al.2b involves heating an epoxide (or diol) with zinc chlo-
SYNTHESIS 2005, No. 10, pp 1625–1630
Advanced online publication: 07.04.2005
DOI: 10.1055/s-2005-865298; Art ID: P00905SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
5

1626
M. Góra et al.
PAPER
Table 1 Naphthylcycloalkenes 3a–l and Naphthylcycloalkanones 4a–l Prepared
General Structure of
Target Ketone
Compound Substituents and
Yield of Alkene 3
(%)/Isolation
Methoda
Oxidation
Procedurea ment
Procedurea
Rearrange-
Yield of Ketone 4 (%)/
a–l
a
b
c
Ring Size
Isolation Methoda
(CH2)n
O
R1, R2, R3 = H,
n = 1
62 (Et2O)/A
65 (Et2O)/A
53 (THF)/A
63 (THF)/A
58 (Et2O)/A
66 (Et2O)/A
51 (Et2O)/A
65 (Et2O)/A
D
D
E
E
D
E
D
D
E
E
E
E
F or G
59/A, then B
(MeOH)
R1, R2, R3 = H,
n = 2
F or G
63/A, then B
(cyclohexane)
R3
R1
R2
R1, R3 = H,
G
11b/A, then C
(SiO2/CHCl3)
R2 = OCH3, n = 1
d
e
R1, R3 = H,
G
57/C (SiO2/CHCl3)
R2 = OCH3, n = 2
R1, R3 = H,
F
53/A, then C
(SiO2/toluene)
R2 = CH3, n = 1
f
R1, R3 = H,
G
46/C (SiO2/CHCl3)
R2 = CH3, n = 2
g
h
i
R1, R2, R3 = H,
n = 1
F or G
60/C (SiO2/CHCl3),
then B (MeOH)
(CH2)n
O
R1, R2, R3 = H,
n = 2
F or G
48/C (SiO2/CHCl3),
then B (MeOH)
R3
R1
R2
R1, R2 = H,
51 (THF)/A,then B
(MeOH)
H
G
G
G
59/C (SiO2/CHCl3)
R3 = OCH3, n = 1
j
R1, R2 = H,
51 (THF)/B
(MeOH)
66/B (MeOH)
R3 = OCH3, n = 2
k
l
R2, R3 = H,
68 (THF)/A, then C
(SiO2/toluene)
50/C (SiO2/toluene)
30/C (SiO2/toluene)
R1 = OCH3, n = 1
R2, R3 = H,
66 (THF)/A, then C
(SiO2/toluene)
R1 = OCH3, n = 2
a A: vacuum distillation; B: crystallization; C: column chromatography; D: H2O2/HCO2H; E: MCPBA; F: ZnCl2; G: H2SO4/EtOH–H2O; H:
spontaneously.
a The main product was 2-(4-methoxy-1-naphthyl)cyclopent-2-en-1-one (4m, 21% yield).
ride under reduced pressure, and it works well only for un- respective ketones in satisfactory yields. Moreover, naph-
substituted naphthalene derivatives.
thylcycloalkanones obtained in this way were more easily
purified due to formation of smaller amounts of by-prod-
ucts.
Methoxy substituted compounds (n = 1), under these con-
ditions undergo polymerization and decomposition or cy-
clization (n = 2) to methoxyfluoranthenes.13 For this Summarizing, we have optimized the oxidation proce-
reason our attention was turned to dilute (ethanol–water dures of various naphthylcycloakenes and epoxide (diol)
mixture) sulfuric acid as mild rearrangement catalyst sys- rearrangement leading to naphthylcycloalkanones. The
tem. This method allowed for smooth and efficient con- method was useful in large-scale syntheses of naphthylcy-
version of all naphthylcycloalkadiols and epoxides to the cloalkanones possessing different substituents in naphtha-
lene moiety.
(CH2)n
(CH2)n
O
The 1H NMR and 13C NMR spectra were recorded in CDCl3 solu-
tion with Bruker AMX-500 spectrometer at 500 MHz and 125
MHz, respectively. The chemical shifts were reported in ppm rela-
tive to TMS or CDCl3. IR spectra (reported in cm–1) were measured
with Bruker IFS 48FT or EQUINOX 55 spectrometers as KBr pel-
lets or neat. Elemental analyses were performed with EuroEA Ele-
mental Analyzer. Melting points were determined with Boetius type
apparatus or in sealed capillaries and are uncorrected. Column chro-
matography was performed on silica gel 60 (70–230 mesh). Et2O
and THF for Grignard reactions were dried and distilled over sodi-
iv, v
R3
R1
R3
R1
R2
R2
3a–l
4a–l
R1, R2, R3 = H, CH3, OCH3
n = 1, 2
Scheme 2 iv) H2O2/HCO2H or MCPBA; v) ZnCl2 or H2SO4
Synthesis 2005, No. 10, 1625–1630 © Thieme Stuttgart · New York

PAPER
Synthesis of 2-Naphthylcycloalkanones
1627
um benzophenone ketyl. For all epoxidations, a commercially avail-
able MCPBA (m-chloroperbenzoic acid 70%) was used.
13C NMR (CDCl3): d = 22.37, 23.34, 25.63, 31.29, 55.45, 103.36,
122.17, 124.61, 124.81, 125.62, 125.73, 126.03, 127.13, 132.39,
135.59, 137.70, 154.26.
2-Naphthylcycloalkenes 3a–l; General Procedure
A solution of cycloalkanone (0.3 mol) in anhyd Et2O (or THF) (50
mL) was added dropwise with vigorous stirring, to the cold Grig-
nard reagent prepared from appropriate bromonaphthalene (0.3
mol) in anhyd Et2O (or THF) (250 mL). The reaction mixture was
strirred for an additional 3 h and then hydrolyzed with sat. aq NH4Cl
solution (100 mL). The organic layer was separated and after re-
moval of the solvent, formic acid (85%, 200 mL) was added to the
crude alcohol. The reaction mixture was refluxed with stirring for 1
h and after dilution with cold H2O (300 mL), the crude naphthylcy-
cloalkene was extracted with toluene (3 × 70 mL). Toluene and
traces of formic acid were removed in vacuo and the product naph-
thylcycloalkene was further purified (Methods A–C, Table 1).
1-Cyclopent-1-en-1-yl-4-methylnaphthalene (3e)
Bp 110–115 °C/0.5 mmHg.
IR (neat): 3067, 2947, 2844, 1591, 1390, 758 cm–1.
1H NMR (CDCl3): d = 2.04–2.10 (m, 2 H), 2.58–2.62 (m, 2 H), 2.64
(s, 3 H), 2.75–2.79 (m, 2 H), 5.86–5.88 (m, 1 H), 7.20–7.23 (m, 2
H), 7.42–7.48 (m, 2 H), 7.96 (dd, 1 H, J = 7.8, 1.8 Hz), 8.15 (dd, 1
H, J = 7.8, 1.6 Hz).
13C NMR (CDCl3): d = 19.49, 23.96, 33.80, 37.93, 124.42 (2 C),
125.32, 125.47, 126.16, 126.51, 130.25, 131.62, 132.93, 133.11,
135.62, 142.61.
Anal. Calcd for C16H16: C, 92.26; H, 7.74. Found: C, 92.11; H, 7.73.
1-Cyclopent-1-en-1-ylnaphthalene (3a)
1-Cyclohex-1-en-1-yl-4-methylnaphthalene (3f)
Bp 132–134 °C/0.5 mmHg; mp 36–37 °C (Lit.15 bp 118–120 °C/
0.04 mmHg; mp 37 °C).
Bp 102–104 °C/0.2 mmHg (Lit.14 bp 122–123 °C/0.5 mmHg).
IR (neat): 3049, 2954, 1507, 1441, 1395, 777 cm–1.
1H NMR (CDCl3): d = 2.04–2.10 (m, 2 H), 2.58–2.62 (m, 2 H),
2.76–2.81 (m, 2 H), 5.91–5.92 (m, 1 H), 7.32 (dd, 1 H, J = 7.1, 1.2
Hz), 7.38 (dd, 1 H, J = 8.1, 7.1 Hz), 7.40–7.44 (m, 2 H), 7.68 (d, 1
H, J = 8.1 Hz), 7.78–7.80 (m, 1 H), 8.14–8.16 (m, 1 H).
13C NMR (CDCl3): d = 24.01, 33.94, 37.86, 124.76, 125.42, 125.69,
125.78, 126.00, 127.16, 128.47, 130.71, 131.57, 133.97, 137.27,
142.39.
IR (KBr): 3065, 2923, 2832, 1434, 1387, 757 cm–1.
1H NMR (CDCl3): d = 1.74–1.79 (m, 2 H), 1.81–1.86 (m, 2 H),
2.23–2.27 (m, 2 H), 2.34–2.37 (m, 2 H), 2.66 (s, 3 H), 5.72–5.75 (m,
1 H), 7.14 (d, 1 H, J = 7.0 Hz), 7.24 (dd, 1 H, J = 7.2, 0.8 Hz), 7.43–
7.49 (m, 2 H), 7.98 (dd, 1 H, J = 7.5, 1.5 Hz), 8.02 (dd, 1 H, J = 7.5,
1.5 Hz).
13C NMR (CDCl3): d = 19.37, 22.32, 23.27, 25.56, 31.23, 124.33,
124.48, 125.13, 125.32, 126.17, 126.43, 127.10, 131.53, 132.69,
132.78, 137.90, 141.52.
1-Cyclohex-1-en-1-ylnaphthalene (3b)
Bp 125–129 °C/0.5 mmHg (Lit.15 bp 125 °C/0.08 mmHg).
IR (neat): 3055, 2929, 1586, 1435, 1391, 783 cm–1.
2-Cyclopent-1-en-1-ylnaphthalene (3g)
Bp 150–154 °C/1 mmHg; mp 84–85 °C (Lit.14 mp 85–86 °C).
1H NMR (CDCl3): d = 1.74–1.79 (m, 2 H), 1.80–1.86 (m, 2 H),
2.23–2.27 (m, 2 H), 2.35–2.38 (m, 2 H), 5.74–5.77 (m, 1 H), 7.25
(dd, 1 H, J = 7.0, 1.2 Hz), 7.38 (dd, 1 H, J = 8.2, 7.0 Hz), 7.42–7.45
(m, 2 H), 7.71 (d, 1 H, J = 8.2 Hz), 7.80–7.83 (m, 1 H), 7.99–8.02
(m, 1 H).
13C NMR (CDCl3): d = 22.28, 23.22, 25.52, 31.04, 124.79, 125.41,
125.46, 125.47, 125.82, 126.65, 127.21, 128.22, 131.43, 133.75,
137.66, 143.10.
IR (KBr): 3047, 2949, 2847, 1585, 1285, 845 cm–1.
1H NMR (CDCl3): d = 2.02–2.08 (m, 2 H), 2.55–2.59 (m, 2 H),
2.79–2.83 (m, 2 H), 6.30–6.32 (m, 1 H), 7.38–7.44 (m, 2 H), 7.67
(dd, 1 H, J = 8.6, 1.8 Hz), 7.70 (s, 1 H), 7.73 (d, 1 H, J = 8.6 Hz),
7.76–7.79 (m, 2 H).
13C NMR (CDCl3): d = 23.34, 33.17, 33.50, 124.07, 124.19, 125.50,
126.05, 126.99, 127.56, 127.66, 128.04, 132.55, 133.60, 134.15,
142.42.
1-Cyclopent-1-en-1-yl-4-methoxynaphthalene (3c)
Bp 145–150 °C/0.5 mmHg.
IR (neat): 3074, 2949, 1585, 1462, 1101, 763 cm–1.
2-Cyclohex-1-en-1-ylnaphthalene (3h)
Bp 133–135 °C/0.5 mmHg; mp 58–59 °C (Lit.14 mp 60–61 °C).
1H NMR (CDCl3): d = 2.04–2.09 (m, 2 H), 2.58–2.63 (m, 2 H),
2.75–2.79 (m, 2 H), 3.95 (s, 3 H), 5.86–5.88 (m, 1 H), 6.73 (d, 1 H,
J = 8.0 Hz), 7.24 (d, 1 H, J = 8.0 Hz), 7.42–7.48 (m, 2 H), 8.10–8.12
(m, 1 H), 8.27–8.29 (m, 1 H).
13C NMR (CDCl3): d = 23.85, 33.68, 37.72, 55.45, 103.30, 122.17,
124.59, 124.89, 125.64, 125.81, 126.16, 129.46, 129.61, 132.38,
142.24, 154.46.
IR (KBr): 3053, 2926, 2856, 1593, 1276, 742 cm–1.
1H NMR (CDCl3): d = 1.67–1.72 (m, 2 H), 1.81–1.85 (m, 2 H),
2.24–2.28 (m, 2 H), 2.51–2.55 (m, 2 H), 6.28 (m, 1 H), 7.38–7.44
(m, 2 H), 7.58 (dd, 1 H, J = 8.6, 1.8 Hz), 7.76 (s, 1 H), 7.74–7.79
(m, 3 H).
13C NMR (CDCl3): d = 22.21, 23.11 26.03, 27.40, 123.09, 123.82,
125.30, 125.48, 125.90, 127.45, 127.55, 128.02, 132.44, 133.58,
136.39, 139.84.
Anal. Calcd for C16H16O: C, 85.68; H, 7.13. Found: C, 85.75; H,
7.04.
2-Cyclopent-1-en-1-yl-6-methoxynaphthalene (3i)
Mp 147.5–148 °C (Lit.17 mp 148 °C).
1-Cyclohex-1-en-1-yl-4-methoxynaphthalene (3d)
Bp 145–150 °C/0.5 mmHg; mp 44–45 °C (Lit.16 mp 44–45 °C).
IR (KBr): 3060, 2951, 1485, 1262, 1030, 816 cm–1.
IR (neat): 3067, 2931, 1587, 1461, 1101, 765 cm–1.
1H NMR (CDCl3): d = 2.02–2.08 (m, 2 H), 2.54–2.59 (m, 2 H),
2.78–2.83 (m, 2 H), 3.90 (s, 3 H), 6.25–6.26 (m, 1 H), 7.09–7.12 (m,
2 H), 7.64–7.65 (m, 3 H), 7.69 (d, 1 H, J = 8.6 Hz).
13C NMR (CDCl3): d = 23.31, 33.16, 33.38, 55.21, 105.86, 118.61,
123.90, 124.67, 125.77, 126.51, 128.95, 129.48, 132.13, 133.62,
142.40, 157.50.
1H NMR (CDCl3): d = 1.73–1.77 (m, 2 H), 1.80–1.85 (m, 2 H),
2.22–2.26 (m, 2 H), 2.32–2.35 (m, 2 H), 3.94 (s, 3 H), 5.72–5.74 (m,
1 H), 6.72 (d, 1 H, J = 7.8 Hz), 7.14 (d, 1 H, J = 7.8 Hz), 7.41–7.46
(m, 2 H), 7.93–7.94 (m, 1 H), 8.26–8.28 (m, 1 H).
Synthesis 2005, No. 10, 1625–1630 © Thieme Stuttgart · New York

1628
M. Góra et al.
PAPER
2-Cyclohex-1-en-1-yl-6-methoxynaphthalene (3j)
Method G: The crude diol (epoxide) obtained as above was dis-
solved in EtOH (200 mL), treated with solution of conc. H2SO4 (40
g) in H2O (200 mL) and refluxed for 1 h. The EtOH was removed
from the mixture under reduced pressure and the residue was ex-
tracted with CHCl3 (3 × 100 mL). The solvent was evaporated from
the combined organic extracts and the product ketone was isolated
as described in Table 1.
Mp 127 °C (Lit.17 mp 124–126 °C).
IR (KBr): 3058, 2924, 1600, 1234, 1034, 857 cm–1.
1H NMR (CDCl3): d = 1.86–1.71 (m, 2 H), 1.79–1.84 (m, 2 H),
2.23–2.26 (m, 2 H), 2.49–2.52 (m, 2 H), 3.89 (s, 3 H), 6.22–6.27 (m,
1 H), 7.08–7.11 (m, 2 H), 7.55 (dd, 1 H, J = 8.6, 1.8 Hz), 7.64 (d, 1
H, J = 8.6 Hz), 7.68 (m, 2 H).
13C NMR (CDCl3): d = 22.23, 23.12, 25.97, 27.37, 55.22, 105.65,
118.60, 122.92, 124.24, 124.56, 126.43, 128.97, 129.49, 133.45,
136.29, 137.72, 157.36.
2-(1-Naphthyl)cyclopentanone (4a)
Bp 155–160 °C/1 mmHg; mp 90–91 °C (Lit.2b bp 170–174 °C/0.8
mmHg; mp 91–93 °C).
IR (KBr): 2964, 2865, 1730, 1399, 1144, 786 cm–1.
2-Cyclopent-1-en-1-yl-3-methoxynaphthalene (3k)
Bp 135–140 °C/0.5 mmHg; mp 68 °C.
IR (KBr): 3046, 2945, 2841, 1252, 1172, 747 cm–1.
1H NMR (CDCl3): d = 1.86–1.95 (m, 2 H), 2.48–2.53 (m, 2 H),
2.74–2.79 (m, 2 H), 3.85 (s, 3 H), 6.48–6.49 (m, 1 H), 7.15 (s, 1 H),
7.18–7.31 (m, 2 H), 7.58–7.66 (m, 3 H).
13C NMR (CDCl3): d = 22.88, 34.13, 35.43, 55.21, 105.35, 123.69,
125.98, 126.11, 127.60, 127.66, 127.85, 128.72, 131.61, 133.32,
139.23, 156.38.
1H NMR (CDCl3): d = 1.99–2.09 (m, 1 H), 2.16–2.24 (m, 2 H),
2.41–2.49 (m, 1 H), 2.54–2.64 (m, 2 H), 4.06 (dd, 1 H, J = 9.7, 5.1
Hz), 7.24 (d, 1 H, J = 7.1 Hz), 7.42 (dd, 1 H, J = 8.1, 7.2 Hz), 7.45–
7.51 (m, 2 H), 7.75 (d, 1 H, J = 8.2 Hz), 7.83–7.89 (m, 2 H).
13C NMR (CDCl3): d = 21.08, 32.35, 38.92, 52.24, 123.57, 124.99,
125.42, 125.58, 126.00, 127.58, 128.90, 132.00, 134.02, 135.39,
218.54.
2-(1-Naphthyl)cyclohexanone (4b)
Bp 155–160 °C/1 mmHg; mp 80–82 °C (Lit.18 bp 164–168 °C/0.6
mmHg, mp 82–83 °C).
Anal. Calcd for C16H16O: C, 85.68; H, 7.13. Found: C, 85.73; H,
7.06.
IR (KBr): 2942, 2860, 1708, 1449, 1122, 781 cm–1.
1H NMR (CDCl3): d = 1.85–1.94 (m, 2 H), 2.10–2.13 (m, 1 H),
2.23–2.31 (m, 2 H), 2.38–2.43 (m, 1 H), 2.61–2.68 (m, 2 H), 4.35
(dd, 1 H, J = 12.6, 5.3 Hz), 7.35 (d, 1 H, J = 7.1 Hz), 7.43–7.48 (m,
3 H), 7.71–7.73 (m, 1 H), 7.77 (d, 1 H, J = 8.2 Hz), 7.84–7.87 (m, 1
H).
13C NMR (CDCl3): d = 25.89, 27.86, 34.25, 42.59, 53.30, 123.24,
125.25, 125.29, 125.33, 125.84, 127.59, 128.97, 131.76, 133.77,
135.18, 209.97.
2-Cyclohex-1-en-1-yl-3-methoxynaphthalene (3l)
Bp 150 °C/0.5 mmHg.
IR (neat): 3053, 2930, 1468, 1429, 1170, 745 cm–1.
1H NMR (CDCl3): d = 1.68–1.78 (m, 4 H), 2.19–2.23 (m, 2 H),
2.39–2.42 (m, 2 H), 3.89 (s, 3 H), 5.83–5.85 (m, 1 H), 7.06 (s, 1 H),
7.26–7.29 (m, 1 H), 7.35–7.37 (m, 1 H), 7.55 (s, 1 H), 7.68 (d, 1 H,
J = 8.1 Hz), 7.70 (d, 1 H, J = 8.1 Hz).
13C NMR (CDCl3): d = 22.23, 23.06, 25.74, 29.02, 55.36, 105.16,
123.59, 125.76, 126.22, 126.49, 127.39, 128.08, 128.91, 133.65,
135.63, 137.75, 155.94.
2-(4-Methoxy-1-naphthyl)cyclopentanone (4c)
Bp 190 °C/0.5 mmHg.
Anal. Calcd for C17H18O: C, 85.67; H, 7.61. Found: C, 85.16; H,
7.43.
IR (KBr): 2959, 1732, 1583, 1259, 1091, 762 cm–1.
1H NMR (CDCl3): d = 1.99–2.04 (m, 1 H), 2.13–2.20 (m, 2 H),
2.39–2.46 (m, 1 H), 2.52–2.60 (m, 2 H), 3.93–3.99 (m, 1 H), 3.96
(s, 3 H), 6.75 (d, 1 H, J = 7.9 Hz), 7.13 (d, 1 H, J = 7.9 Hz), 7.45–
7.52 (m, 2 H), 7.80 (d, 1 H, J = 8.2 Hz), 8.31 (dd, 1 H, J = 8.2, 1.1
Hz).
13C NMR (CDCl3): d = 21.98, 32.37, 38.83, 51.87, 55.45, 103.42,
122.71, 123.36, 124.91, 124.99, 126.13, 126.47, 127.31, 132.83,
154.71, 218.81.
2-Naphthylcycloalkanones 4a–l; General Oxidation and Epoxi-
dation Procedures
Method D: To a vigorously stirred solution of 1-naphthylcycloalk-
ene 3 (0,2 mol) in acetone (100 mL) was added slowly a solution of
30% H2O2 (22.7 g, 0.2 mol) in 85% formic acid (100 mL 2.2 mol)
keeping the temperature between 35–40 °C. Then, the mixture was
allowed to stand overnight at r.t. A solution NaOH (84.0 g, 2.1 mol)
in H2O (200 mL) was added slowly under cooling in an ice-bath and
the mixture was extracted with EtOAc (3 × 150 mL). The combined
extracts, after removal of solvent yielded a crude mixture of diol,
formic acid esters and epoxide.
Anal. Calcd for C16H16O2: C, 80.00; H, 6.67. Found: C, 80.07; H,
6.59.
2-(4-Methoxy-1-naphthyl)cyclohexanone (4d)
Method E: 1-Naphthylcycloalkene 3 (0.2 mol) was dissolved in a
mixture of EtOAc–CHCl3 (1:2, 150 mL) at 4 °C and a cold solution
of MCPBA (49.3 g, 0.2 mol) in EtOAc (250 mL) was added. The
reaction mixture was kept in the refrigerator for 12 h and then shak-
en with solution of NaOH (8.0 g, 0.2 mol) in H2O (500 mL). The
organic layer was separated, washed with H2O to neutral pH and
concentrated to give the crude epoxide.
Mp 110–110.5 °C.
IR (neat): 2937, 1696, 1463, 1273, 1094, 759 cm–1.
1H NMR (CDCl3): d = 1.86–1.96 (m, 2 H), 2.08–2.13 (m, 1 H),
2.19–2.27 (m, 2 H), 2.35–2.41 (m, 1 H), 2.58–2.63 (m, 2 H), 3.98
(s, 3 H), 4.25 (dd, 1 H, J = 12.5, 5.2 Hz), 6.80 (d, 1 H, J = 8.0 Hz),
7.24 (d, 1 H, J = 8.0 Hz), 7.42–7.48 (m, 2 H), 7.64 (dd, 1 H, J = 8.0,
1.6 Hz), 8.30–8.32 (m, 1 H).
Rearrangement of Diol (Epoxide); General Procedures
13C NMR (CDCl3): d = 25.96, 27.89, 34.36, 42.56, 52.89, 55.40,
103.34, 122.74, 123.00, 124.64, 125.15, 125.91, 126.32, 127.15,
132.61, 154.68, 210.26.
Method F: The crude diol (epoxide) obtained as above was heated
with anhyd ZnCl2 (20 g) at 100–110 °C for 1 h at 20 mm Hg (water
pump vacuum). The cooled dark mixture was extracted with CHCl3.
The combined organic extracts were washed with H2O, and after re-
moval of solvent, the product ketone was isolated (Table 1).
Anal. Calcd for C17H18O2: C, 80.31; H, 7.09. Found: C, 80.23; H,
7.12.
Synthesis 2005, No. 10, 1625–1630 © Thieme Stuttgart · New York

PAPER
Synthesis of 2-Naphthylcycloalkanones
1629
2-(4-Methyl-1-naphthyl)cyclopentanone (4e)
Bp 180 °C/0.5 mmHg; mp 66–67 °C.
Anal. Calcd for C16H16O2: C, 80.00; H, 6.67. Found: C, 80.07; H,
6.56.
IR (KBr): 2962, 1734, 1394, 1136, 818, 763 cm–1.
2-(6-Methoxy-2-naphthyl)cyclohexanone (4j)
1H NMR (CDCl3): d = 2.01–2.09 (m, 1 H), 2.15–2.24 (m, 2 H),
2.40–2.48 (m, 1 H), 2.53–2.63 (m, 2 H), 2.66 (s, 3 H), 4.02–4.06 (m,
1 H), 7.12 (d, 1 H, J = 7.2 Hz), 7.26 (d, 1 H, J = 7.2 Hz), 7.48–7.53
(m, 2 H), 7.88–7.90 (m, 1 H), 8.01–8.04 (m, 1 H).
13C NMR (CDCl3): d = 19.41, 21.05, 32.40, 38.87, 52.13, 124.10,
124.68, 124.93, 125.42, 125.61, 126.23, 132.03, 133.14, 133.58,
133.60, 218.5.
Mp 135 °C (Lit.19 mp 133–134.5 °C).
IR (KBr): 2949, 1709, 1606, 1236, 1036, 846 cm–1.
1H NMR (CDCl3): d = 1.82–1.87 (m, 2 H), 2.02–2.07 (m, 1 H),
2.13–2.20 (m, 2 H), 2.30–2.34 (m, 1 H), 2.47–2.57 (m, 2 H), 3.75
(dd, 1 H, J = 11.8, 5.4 Hz), 3.90 (s, 3 H), 7.10–7.12 (m, 2 H), 7.23
(dd, 1 H, J = 8.4, 1.8 Hz), 7.51 (d, 1 H, J = 0.8 Hz), 7.66–7.71 (m,
2 H).
13C NMR (CDCl3): d = 25.24, 27.77, 34.98, 42.13, 55.24, 57.19,
105.67, 118.61, 126.66, 126.70, 127.40, 128.95, 129.16, 133.58,
134.03, 157.51, 210.42.
Anal. Calcd for C16H16O: C, 85.71; H, 7.14. Found: C, 85.64; H,
7.22.
2-(4-Methyl-1-naphthyl)cyclohexanone (4f)
Mp 134–134.5 °C.
IR (KBr): 2920, 1695, 1440, 1126, 832, 758 cm–1.
2-(3-Methoxy-2-naphthyl)cyclopentanone (4k)
Mp 88–89 °C.
1H NMR (CDCl3): d = 1.86–1.97 (m, 2 H), 2.08–2.14 (m, 1 H),
2.20–2.29 (m, 2 H), 2.35–2.40 (m, 1 H), 2.58–2.65 (m, 2 H), 2.67
(s, 3 H), 4.31 (dd, 1 H, J = 12.5, 5.2 Hz), 7.23 (d, 1 H, J = 7.2 Hz),
7.30 (d, 1 H, J = 7.2 Hz), 7.43–7.50 (m, 2 H), 7.71 (dd, 1 H, J = 7.4,
1.6 Hz), 8.01 (dd, 1 H, J = 7.8, 1.4 Hz).
13C NMR (CDCl3): d = 19.47, 25.94, 27.88, 34.27, 42.58, 53.23,
123.77, 124.94, 125.00, 125.15, 125.47, 126.21, 131.83, 132.93,
133.39, 133.53, 210.04.
IR (KBr): 2924, 1733, 1471, 1261, 1110, 870 cm–1.
1H NMR (CDCl3): d = 1.78–1.85 (m, 1 H), 2.06–2.19 (m, 2 H),
2.26–2.31 (m, 1 H), 2.34–2.37 (m, 2 H), 3.37–3.43 (m, 1 H), 3.77
(s, 3 H), 7.02 (s, 1 H), 7.20–7.23 (m, 1 H), 7.28–7.31 (m, 1 H) 7.44
(s, 1 H), 7.60 (d, 2 H, J = 9.2 Hz).
13C NMR (CDCl3): d = 21.47, 31.09, 38.17, 52.85, 55.22, 105.95,
123.73, 125.97, 126.30, 127.19, 128.78, 129.70, 129.79, 133.85,
155.32, 218.75.
Anal. Calcd for C17H18O: C, 85.67; H, 7.61. Found: C, 85.63; H,
7.70.
Anal. Calcd for C16H16O: C, 80.00; H, 6.67. Found: C, 79.94; H,
6.58.
2-(2-Naphthyl)cyclopentanone (4g)
2-(3-Methoxy-2-naphthyl)cyclohexanone (4l)
Yellow oil.
IR (neat): 2937, 1710, 1473, 1022, 746, 476 cm–1.
1H NMR (CDCl3): d = 1.80–1.87 (m, 2 H), 2.03–2.06 (m, 1 H),
2.15–2.20 (m, 2 H), 2.28–2.32 (m, 1 H), 2.52–2.55 (m, 2 H), 3.87
(s, 3 H), 4.01–4.04 (m, 1 H), 7.11 (s, 1 H), 7.28–7.31 (m, 1 H), 7.37–
7.40 (m, 1 H), 7.54 (s, 1 H), 7.69–7.72 (m, 2 H).
13C NMR (CDCl3): d = 25.66, 27.56, 33.15, 42.26, 51.53, 55.39,
105.21, 123.51, 125.86, 126.30, 127.44, 127.77, 128.72, 129.69,
133.73, 155.64, 209.75.
Mp 81–82 °C (Lit.2b mp 80–83 °C).
IR (KBr): 2963, 1730, 1405, 1145, 1115, 860 cm–1.
1H NMR (CDCl3): d = 1.90–2.00 (m, 1 H), 2.14–2.25 (m, 2 H),
2.28–2.36 (m, 1 H), 2.46–2.57 (m, 2 H), 3.47 (dd, 1 H, J = 8.6, 8.2
Hz), 7.30 (dd, 1 H, J = 8.5, 1.8 Hz), 7.41–7.46 (m, 2 H), 7.63 (s, 1
H), 7.76–7.80 (m, 2 H), 7.73 (d, 1 H, J = 8.5 Hz).
13C NMR (CDCl3): d = 20.87, 31.71, 38.47, 55.36, 125.64, 126.03,
126.31, 126.74, 127.57, 127.64, 128.23, 132.38, 133.38, 135.85,
218.10.
2-(2-Naphthyl)cyclohexanone (4h)
Anal. Calcd for C17H18O: C, 80.31; H, 7.09. Found: C, 80.45; H,
7.24.
Mp 82–83 °C (Lit.2b mp 83.5–84.5 °C).
IR (KBr): 2932, 1708, 1508, 1301, 1122, 816 cm–1.
2-(4-Methoxy-1-naphthyl)cyclopent-2-en-1-one (4m)
Bp 145–150 °C/0.5 mmHg.
IR (KBr): 3074, 2933, 1692, 1586, 1089, 789 cm–1.
1H NMR (CDCl3): d = 2.66–2.70 (m, 2 H), 2.84–2.87 (m, 2 H), 4.02
(s, 3 H), 6.85 (d, 1 H, J = 7.8 Hz), 7.33 (d, 1 H, J = 7.9 Hz), 7.46–
7.50 (m, 2 H), 7.74–7.77 (m, 2 H), 8.31–8.33 (m, 1 H).
13C NMR (CDCl3): d = 26.81, 34.98, 55.52, 103.33, 122.00, 122.32,
124.81, 125.06, 125.78, 126.50, 127.07, 132.35, 144.67, 155.66,
161.65, 208.13.
1H NMR (CDCl3): d = 1.81–1.91 (m, 1 H), 2.00–2.07 (m, 1 H),
2.12–2.21 (m, 2 H), 2.31–2.36 (m, 1 H), 2.46–2.58 (m, 2 H), 3.77
(dd, 1 H, J = 12.2, 5.6 Hz), 7.27 (dd, 1 H, J = 8.4, 1.6 Hz), 7.41–
7.46 (m, 2 H), 7.69 (s, 1 H), 7.77–7.81 (m, 3 H).
13C NMR (CDCl3): d = 25.28, 27.79, 35.00, 42.20, 57.43, 125.58,
125.86, 126.96 (2 C), 127.61, 127.71, 127.79, 132.56, 133.49,
136.41, 210.25.
2-(6-Methoxy-2-naphthyl)cyclopentanone (4i)
Mp 112–113 °C.
IR (KBr): 2959, 1738, 1607, 1234, 1030, 850 cm–1.
Anal. Calcd for C16H14O2: C, 80.64; H, 5.92. Found: C, 80.56; H,
6.03.
1H NMR (CDCl3): d = 1.94–2.00 (m, 1 H), 2.17–2.25 (m, 2 H),
2.29–2.37 (m, 1 H), 2.46–2.58 (m, 2 H), 3.44–3.48 (m, 1 H), 3.91
(s, 3 H), 7.10–7.13 (m, 2 H), 7.28 (dd, 1 H, J = 8.4, 1.8 Hz), 7.57 (s,
1 H), 7.68 (d, 1 H, J = 8.8 Hz), 7.71 (d, 1 H, J = 8.4 Hz).
13C NMR (CDCl3): d = 20.83, 31.70, 38.41, 55.07, 55.22, 105.63,
118.80, 126.48, 126.77, 127.08, 128.93, 129.12, 133.52, 157.53,
217.99.
Acknowledgment
This work was financed in part by the State Committee for Scienti-
fic Research of Poland (KBN) within Grant No. 3 P04G 033 24. We
also wish to thank Prof. E. Biehl for his helpful advices.
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M. Góra et al.
PAPER
(9) Kimura, M.; Kobayashi, K.; Yamamoto, Y.; Sawaki, Y.
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Synthesis 2005, No. 10, 1625–1630 © Thieme Stuttgart · New York