A new and efficient synthesis of indenone

Article abstract of DOI:10.1081/SCC-100104416

Reaction of dichloroketone 2 with NEt₃ gave indenone (4) in high yield. Catodic reaction of 2 in the presence of C/Pt electrodes afforded the rearranged product 3 in high yield besides a small amount of chlorohydroxyketone 5. Reaction of rearranged dichloroketone 3 with NEt₃ provided indenone (4) as the sole product. The mechanism of these reaction was discussed.

Full text of DOI:10.1081/SCC-100104416

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A NEW AND EFFICIENT SYNTHESIS OF INDENONE
Mustafa Zengin a , Arif Daştan b & Metin Balci c
a Department of Chemistry , Sakarya University , Adapazari, 54100, Turkey
b Department of Chemistry , Atatürk University , Erzurum, 25240, Turkey
c Department of Chemistry , Middle East Technical University , Ankara, 06531, Turkey
Published online: 09 Nov 2006.
To cite this article: Mustafa Zengin , Arif Daştan & Metin Balci (2001) A NEW AND EFFICIENT SYNTHESIS OF INDENONE,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 31:13,
1993-1999, DOI: 10.1081/SCC-100104416
To link to this article: http://dx.doi.org/10.1081/SCC-100104416
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SYNTHETIC COMMUNICATIONS, 31(13), 1993–1999 (2001)
A NEW AND EFFICIENT SYNTHESIS
OF INDENONE
Mustafa Zengin,1 Arif Das tan,2 and Metin Balcı3,
*
1Department of Chemistry, Sakarya University, 54100
Adapazarı, Turkey
2Department of Chemistry, Ataturk University,
25240 Erzurum, Turkey
3Department of Chemistry, Middle East Technical University,
06531 Ankara, Turkey
ABSTRACT
Reaction of dichloroketone 2 with NEt3 gave indenone (4) in
high yield. Catodic reaction of 2 in the presence of C/Pt elec-
trodes afforded the rearranged product 3 in high yield besides
a small amount of chlorohydroxyketone 5. Reaction of rear-
ranged dichloroketone 3 with NEt3 provided indenone (4) as
the sole product. The mechanism of these reaction was
discussed.
A rapid growth on the synthetic work of indenones took place in the
last three decades. Indenones are useful intermediates1 in the synthesis of a
variety of molecules, including the C-nor D-homosteroid ring system,2
photochromic indenone oxides,3 2,4- and 3,4-disubstituted-1-naphtols,4 gib-
berellines,5 indanones6 and indenes.7 A great deal of work has been directed
*Corresponding author.
1993
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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ZENGIN, DASTAN, AND BALCI
towards the synthesis of the hindered fungicidally active 2-cyana-3-alkyl-
1-indenones8 and various 2,3-diaryl-1-indenones.4,9–11 Furthermore, the
derivatives of indanone exhibit biological activity12 (e.g., antihypertensive
or bronchodilatory activity) and they serve as synthetic precursors to other
natural products (e.g., steroids or fermentation activators,13 fungicides,8 and
potential estrogen binding receptors.9
Despite the considerable biological and synthetic interest in indenones,
the development of general and flexible synthetic routes to these compounds
still remains a challenging problem. Several procedures for the synthesis of
indanones and indenols have been reported.14 Mainly, two methods have
been directed towards the synthesis of indenone derivatives. The first one1,15
is palladium or aluminium chloride catalysed addition of substituted benzoil
chlorides to acetylenic compounds. The variation of this reaction was
achieved by Gevorgyan and Yamamato14a,b for the synthesis of indanones
and indenols. The second method13,16 involves an intramolecular Friedel-
Crafts acylation of ß-chloro-ß-arylpropionyl chlorides followed by a dihy-
drochlorination reaction. The methodologies for the preparation of
indenone are of rather limited use because of multistep, low yield, irrepro-
ducibility or decomposition of starting material. Several methods for the
conversion of 1-indanone to indenone have been reported.17 Marvel and
Hinman18 converted indanone to 2-acetoxy-1-indanone, and then from
the pyrolyses of this compound they obtained indenone in 8.2% yield.
They also obtained indenone from the bromination of indanone with
NBS, followed by dehydrobromination of 3-bromoindanone. This synthesis
was achieved by Minuti et al.19 with a total of 65.8% yield. The similar
methods have been reported by Bellamy20 (78%) and Tidwell et al.21 (24.7%
yield except the last step). The bromination of 1-indanone with DBMA
(5,5-dibromo-2,2-dimethyl-4,6-dioxo-1,3-dioxane) gives 2-bromoindanone.
The protection of carbonyl group followed by dehydrobromination, yields
indenone ethylene ketal. The removal of the protecting group affords
indenone. Floyd and Allen16 synthesised indenone by the Friedel-Crafts
acylation of ß-chloro-ß-arylpropionyl chlorides followed by a dehydro-
chlorination reaction in 44% yield. In this paper we report a new and
efficient synthesis for the preparation of indenone (4).
The starting material 222 was prepared by the addition of the dichloro-
ketene to cycloheptatriene 1. Reaction of dichloroketone 2 with NEt3 (freshly
distilled over metallic sodium) gave indenone as the sole product. The NMR
spectral studies indicated that dichloroketone 3 was formed initially, which
was then transferred into 4 (Scheme 1). This rearrangement is known as ‘‘cine
rearrangement’’ with the reference to ‘‘cine substitution’’, a commonly used
term for a’ substitution of a-halocyclobutanones by external substituents.23
The intermediate 3 was isolated by an independent reaction. Catodic reaction

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Scheme 1.
of 2 in the presence of C/Pt electrodes gave the rearranged product 3 in 70%
yield besides a small amount of chlorohydroxyketone 5 which has probably
been formed during the column chromatography. The structures of 3 and 5
have been elucidated on the basis of 1H, and 13C NMR data. Treatment of 3
with NEt3 gave indenone as the sole product in 72% yield.
For this rearrangement we propose the following reaction mechanism.
Firstly, the HCl elimination of 3 gives cycloheptatriene derivative 6 which
will be in equilibrium with its valance isomer norcaradiene 7. Further HCl
elimination from 7 can result in the formation of indenone (Scheme 2).
In summary, we have developed an effective and simple synthetic
methodology for the preparation of indenone (4). This methodology may
also be applied to the synthesis of substituted indenones. Investigation of
these types of reactions is currently under progress.
EXPERIMENTAL
General: Melting points are uncorrected. Infrared spectra were
1
obtained from films on NaCl plates on a regular instrument. The H and
13C NMR spectra were recorded on 200- and 60-MHz spectrometers.
Apparent splitting are given in all cases. TLC was carried out on Merck
0.2mm silica gel 60 F254 analytical aluminium plates. Triethyl amine was
freshly distilled over metallic sodium prior to use.

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Scheme 2.
9,9-dichlorobicyclo[5.2.0]nona-2,4-dien-8-one (2)22: A 1L three-necked flask
equipped with a condenser, addition funnel, and N2 inlet was charged with
25 g (0.27 mol) of cycloheptatriene, 52.7 g of Zn-Cu (0.81 mol) and 300 mL
of anhydrous diethyl ether. The suspension was stirred under N2 and a
solution of 58.9 g (0.324 mol) of trichloroacetylchloride and 49.7 g
(0.324 mol) phosphoryltrichloride (distilled from potassium carbonate) in
100 mL of diethyl ether was added dropwise over 3 h. When the addition
of the solution was complete, the mixture was refluxed with stirring for
24 hrs. The reaction mixture was then filtered through a pad celite and
unreacted zinc was washed with 100 mL of diethyl ether. The etheral sol-
ution was washed with saturated NaHCO3, water and dried with MgSO4.
The solvent was than removed in vacuo. The residue was filtered through a
silica gel column (50 g) eluting with ethyl acetate/hexane (1:9) to give 44.0 g
(0.216 mol, 78%) dichloroketone 2 as a pale yellow oil. 1H NMR (200 MHz,
CDCl3): 5.7–6.3 (m, 4H, olefinic), 4.0 (ddd, J ¼ 11.3, 8.7 and 5.2Hz, 1H,
H7), 3.65 (dd, J ¼ 11.3 and 3.4 Hz, 1H, H1), 2.1–2.7 (m, 2H, H6). 13C NMR
(50 MHz, CDCl3): 197.84, 133.47, 131.03, 130.72, 130.67, 79.26, 68.05,
53.24, 29.75. IR (neat, cmꢀ1): 3055, 3010, 3000, 2927, 1829, 1472.
C9H8Cl2O (203.1) calcd. C 53.23, H 3.97; found C 53.12, H 3.91.
The reaction of 9,9-dichloro-bicyclo[5.2.01,7]nona-3,5-diene-8-on (2) with
NEt3: To a magnetically stirred solution of dichloroketone 2 (4.0 g,
19.7 mmol) in 150 mL methylene chloride cooled to 10ꢁC was added drop-
wise a solution of NEt3 (freshly distilled over metallic sodium) (3.98 g,
39.4 mmol) in 10 mL methylene chloride during 15 min. This solution was

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stirred for 2h at 10 ꢁC. The solvent was removed approximately to 10% of
original volume under reduced pressure at room temperature. To magneti-
cally stirred residue was added ether (200 mL). The solution was filtered to
remove the inorganic salts. The precipitated was washed with ether
(3 ꢂ 50 mL). After removal of solvent, the residue was eluted over silica
gel (10 g), with petroleum ether/ethyl ether (97:3) and indenone (4) was
obtained as the sole product. Indenon (1.74 g, 68%), bright yellow oil:
1H-NMR (200 MHz, CDCl3): 7.56 (d, J ¼ 5.9 Hz, A-part of AX system,
1H, H3), 7.45–7.04 (m, 4H, aryl), 5.89 (d, B-part of AX system,
J ¼ 5.9 Hz, 1H, H2). 13C-NMR (50 MHz, CDCl3): 200.17, 151.58, 146.65,
135.56, 132.44, 131.11, 129.21, 124.63, 124.15. IR (NaCl, cmꢀ1): 3029,
2927, 1753, 1727, 1625, 1548, 1472, 1370, 1293, 1191, 1038.
Catodic Reaction of 9,9-dichloro-bicyclo[5.2.01,7]nona-3,5-diene-9-on (2)
in DMF: Into a 50 mL three-electrode H-cell fitted with Pt (anode) and
graphite (cathode) electrodes were placed DMF (30 mL) and lithium per-
chlorate LiClO4 (320 mg, 3 mmol) as electrolyte. Dichloroketone 2 (1.5 g,
7.39 mmol) was added to the cathode departure and after 12.7 Faradays/mol
of electricity have been passed at a constant current of 15 mA (7 d, voltage:
2.1 V) through the solution, the solution was extracted with ether. The
extract was washed with water and dried over MgSO4. After removal of
solvent, the residue was chromatographed over silica gel (100 g), with
hexane/ethyl acetate (97:3) as the eluent. The first fraction identified as
7,9-dichlorobicyclo[5.2.0]nona-2,4-dien-8-one (3): Pale yellow oil, 1.05 g,
70% yield. 1H-NMR (200 MHz, CDCl3): 6.33 (dd, J ¼ 11.2and 5.7 Hz,
1H, H2), 6.22 (dd, J ¼ 10.5 and 4.7 Hz, 1H, H4), 6.15 (dd, 1H, J ¼ 11.2
and 4.7 Hz, H3), 5.95 (dt, J ¼ 10.5 and 6.3 Hz, 1H, H5), 4.79 (d,
J ¼ 8.4 Hz, 1H, H9), 3.22 (dd, J ¼ 8.4 and 5.7 Hz, 1H, H1), 2.59 (d,
J ¼ 6.3 Hz, 2H, H6) 13C-NMR (50 MHz, CDCl3): d 199.11, 133.48, 132.50,
131.25, 130.50, 86.73, 66.61, 55.37, 36.47. IR (NaCl, cmꢀ1): 3055, 2978,
2902, 2851, 1829, 1446, 1268, 1217, 1063, 987, 844, 810.
Then the column was eluted with hexane/ethyl acetate (80:20). As the
second we isolated hydroxy compound 9-chloro-7-dydroxybicyclo[5.2.0]-
nona-2,4-dien-8-one: (5) Pale yellow oil, 27 mg, 2%yield. 1H-NMR
(200 MHz, CDCl3): 6.22–5.92 (m, 4H, H2, H3, H4, and H5), 4.98 (d,
J ¼ 9.9 Hz, 1H, H9), 3.47 (bd, 1H, J ¼ 9.0 Hz, H1), 2.69 (dd, A-part of AB
system, J ¼ 13.8 and 5.0 Hz, 1H, H6a), 2.4 (dd, J ¼ 13.8 and 7.2, 1H, H6b).
13C-NMR (50 MHz, CDCl3): d 205.94, 132.43, 131.93, 131.22, 130.25,
102.54, 65.09, 50.16, 36.17. IR (NaCl, cmꢀ1): 3464, 3055, 2953, 1804,
1727, 1472, 1395, 1344, 1268, 1114, 1089, 936.
The reaction of 7,9-dichlorobicyclo[5.2.0]nona-2,4-dien-8-one (3) with
NEt3: To a magnetically stirred solution of dichloroketone 3 (2.0 g,
9.9 mmol) in 60 mL methylene chloride cooled to 10ꢁC was added dropwise

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ZENGIN, DASTAN, AND BALCI
a solution of NEt3 (freshly distilled over metallic sodium) (1.00 g, 9.9 mmol)
in 5 mL methylene chloride during 15 min. This solution was stirred for 2h
at 10ꢁC. The solvent was removed approximately to 10% of original volume
under the reduced pressure at room temperature. To a magnetically stirred
residue was added ether (150 ml). The solution was filtered to remove the
inorganic salts. The precipitated was washed with ether (3 ꢂ 50 mL). After
removal of solvent, the residue was eluted over silica gel (5 g), with petro-
leum ether/ethyl ether (97:3) and indenone (4) was obtained the sole product
(0.92g, 72% yield).
ACKNOWLEDGMENTS
The authors are indebted to the Department of Chemistry (Ataturk
University) for the financial support of this work.
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Received in the UK July 6, 2000

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