A concise synthesis of 2-benzoyl-1-indanones and 1-indanones from 2-aryl-1-tetralones

Article abstract of DOI:10.1080/00397911.2020.1771370

Methyl-2-(3-oxo-3-aryl) benzoates derived from acid catalyzed air oxidative fragmentation of 2-aryl-1-tetralones were efficiently undergone intramolecular-Claisen condensation in the presence of potassium tertiary butoxide. The resulting 2-benzoyl-1-indanones formed in two-step ring contractions were further subjected to indium triflate mediated retro-Claisen condensation to get 1-indanones.

Full text of DOI:10.1080/00397911.2020.1771370

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A concise synthesis of 2-benzoyl-1-indanones and
1-indanones from 2-aryl-1-tetralones
Anusueya Kumari, Saurabh Kumar Singh, Raj Bahadur Singh, Sabyasachi
Bhunia & Partha Ghosh
To cite this article: Anusueya Kumari, Saurabh Kumar Singh, Raj Bahadur Singh, Sabyasachi
Bhunia & Partha Ghosh (2020): A concise synthesis of 2-benzoyl-1-indanones and 1-indanones
from 2-aryl-1-tetralones, Synthetic Communications, DOI: 10.1080/00397911.2020.1771370
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SYNTHETIC COMMUNICATIONS
https://doi.org/10.1080/00397911.2020.1771370
A concise synthesis of 2-benzoyl-1-indanones and
1
-indanones from 2-aryl-1-tetralones
Anusueya Kumari, Saurabh Kumar Singh, Raj Bahadur Singh, Sabyasachi Bhunia,
and Partha Ghosh
Department of Chemistry, Central University of Jharkhand, Ranchi, India
ABSTRACT
ARTICLE HISTORY
Methyl-2-(3-oxo-3-aryl) benzoates derived from acid catalyzed air oxi-
dative fragmentation of 2-aryl-1-tetralones were efficiently under-
gone intramolecular-Claisen condensation in the presence of
potassium tertiary butoxide. The resulting 2-benzoyl-1-indanones
formed in two-step ring contractions were further subjected to
indium triflate mediated retro-Claisen condensation to get 1-inda-
nones.
Received 12 April 2020
KEYWORD
Air oxidation; 2-benzoyl-1-
indanones; 1-indanone;
retro-Claisen condensation
GRAPHICAL ABSTRACT
Introduction
1
-Indanone and structurally related moieties are widely found in bioactive natural prod-
[
1,2]
ucts, drugs and agrochemicals.
2-benzoyl derivatives of 1-indanones belongs to an
important class of b-dicarbonyl compounds which along with tautomeric 2-hydroxben-
zylidene-1-indanones and structurally related 2-arylidene-1-indanones show diverse bio-
[
3]
logical activities. On the other hand, metal chelates of b-dicarbonyl compounds are
[
4]
well known to have significant material science application potential. Recently transi-
tion metal complexes of 2-benzoyl-1-indanones have been reported to be anticarcino-
genic and also shown properties suitable for potential photovoltaic and luminescence
[
5]
applications. There are several synthetic procedures available to get 2-benzoyl-1-inda-
nones, however, given the dependence of both biological and material properties on
[
1,2,5]
their structural variation, novel synthetic methods are required.
Results and discussions
Recently our group has reported an acid catalyzed auto oxidative fragmentation of 2-
aryl-1-tetralones 1 in presence of methanol and air to generate methyl-2-(3-oxo-3-aryl)
[
6]
benzoates 2 (Scheme 1).
CONTACT Partha Ghosh
partha.ghosh@cuj.ac.in
Department of Chemistry, Central University of Jharkhand,
Brambe, Ranchi 835205, India.
Supplemental data for this article is available online at at publisher’s website.
ß 2020 Taylor & Francis Group, LLC

2
A. KUMARI ET AL.
O
O
O
Ar
O
t
air,TsOH
% MeOH
in toluene
OCH3
Ar
KO Bu
THF, rt
0 min
2
Ar
1
1
O
3
2
3
a, yield : 88% (from 2a),
1a: Ar = Ph
2a: Ar = Ph
3
8% (from 1a, one pot)
Scheme 1. Auto oxidative fragmentation of 2-aryl-1-tetralones followed by intramolecular-Claisen
condensation
The 1,6-dicarbonyl compounds 2 thus obtained should in principle undergo intramo-
[
7]
lecular-Claisen condensation.
Indeed, when 2a was subjected to a stoichiometric
amount of potassium tert-butoxide in THF, 2-benzoyl-1-indanone 3 formed almost
instantly at room temperature with high yield. This condensation allows a two-step for-
mal ring contraction of 2-aryl-tetralone to 2-benzoyl-1-indanone. The ring contraction
[
8]
has been a widely used strategy in synthesis. In particular; synthesis of 1-indanone
derivatives via ring contraction of 1-tetralone has been reported via photofavorsky reac-
[
9]
tion and through a multistep sequence involving stoichiometric thallium (III) nitrate.
In this context, the current method involving air oxidation provides a green alternative
synthesis. The excellent yield obtained under ambient condition obviates further opti-
mization of the condensation reaction (2a!3a). However, reaction did not occur when
the solvent was changed to toluene which posed difficulty to carry out a one-pot con-
version of 1–3. A one-pot two-step protocol in which evaporation of solvent from the
fragmentation reaction (1a!2a) followed by the condensation reaction (2a!3a) in
THF gave the desired compound 3a albeit in lower 38% yield. Hence, we decided to
carry out the condensation step separately.
[
10]
The two-step auto oxidative fragmentation of 2-aryl-1-tetralones
followed by intra-
molecular-Claisen condensation reaction was then carried out in substrates with various
substituents both in tetralone as well as in a-aromatic group and summarized in
Table 1. The fragmentation reaction (4!5) via known procedure gave good yields of
[
11]
5.
Whereas all the condensation reactions (5!6) were found to be fast and com-
pleted within 10 minutes in room temperature with excellent yield. The later reaction
was however found to be sensitive to moisture and a dry solvent is necessary to get
optimum yield. No significant effect of both electron-donating and electron-withdraw-
ing substituents on the outcome of the condensation reaction was observed. The result-
ing indanone derivatives exist exclusively as 2-hydroxyarylidene-1-indanone form 6 in
0
the solid state but in equilibrium with 2-benzoyl-1-indanones 6 in solution with vary-
ing ratios depending on the substitution on aromatic rings (Scheme 2). Compared to
[
5]
the 2-benzoyl-1-indanone 3a the enol form was lower in 6c and higher in both 6b and
1
6
f as observed by H NMR in CDCl . The rich chemistry of b-dicarbonyl compounds
3
especially catalytic asymmetric transformations can be applied for further conversion of
[
12]
6
to various indanone and indane moieties.
One of the straightforward conversion of
b-dicarbonyl compounds is their reaction with alcohols in the presence of lewis acids to
[
13,14]
produce esters via retro-Claisen condensation.
When compound 6a was reacted with ethanol in the presence of catalytic In(OTf) it
3,
chemoselectively yielded 1-indanone 7 as no significant amount of 8 was observed.

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Table 1. 2-Benzoyl-1-indanones from 2-aryl-1-tetralones.
O
O
O
R
R
OH
Ar
R
Ar
OCH3
t
air,TsOH
% MeOH
in toluene
KO Bu
Ar THF, rt
0 min
2
1
4
5
O
6
a
entry
4 (Ar)
R
Products (yield in %)
1
2
3
4
5
6
7
8
4a (p-Me-Ph)
4b (o-Me-Ph)
4c (p-OMe-Ph)
4d (p-Cl-Ph)
4e (3-pyridyl)
4f (Ph)
H
6a (93%)
6b (90%)
6c (92%)
6d (96%)
6e (92%)
6f (93%)
6g (94%)
6h (94%)
OMe
F
4g (p-Me-Ph)
4h (Ph)
All the reactions were run with 0.05 M concentration of the 5 in THF.
a
yields reported are isolated yield. Isolated yields for the conversion of 4 to 5 are 82–90%.
O
O
1
Enol form in CDCl ( H NMR)
3
R
O
R
OH
Ar
3
6
a: 86%
c: 76%
Ar
6f: > 98%
6b: 96%
6'
6
O
O
O
5
mol% In(OTf)3
OEt
OH
Ar
+
ArCOOEt +
Ar
Ethanol, reflux,
72 h
7
8
O
6a
7
8%Yield
Scheme 2. Retro-Claisen condensation of 2-benzoyl-1-indanones/2-hydroxyarylidene-1-indanone.
However, the reaction requires a long time even under the refluxing condition. The
importance of 1-Indanone derivatives continues to attract the attention of the synthetic
[
15]
community for the development of novel methods of their preparation.
The observed
selective retro-Claisen condensation with high yield makes it an attractive method for
the synthesis of 1-Indanones from 2-aryl-1-tetralones.
Retro-Claisen condensation of various substituted 2-benzoyl-1-indanones with n-
butanol in the presence of catalytic In(OTf) are summarized in Table 2. As expected
3
the reaction time shortened under reflux in higher boiling n-butanol compare to etha-
nol. The reaction was also found to be faster with electron-deficient a-aryl group
(entries 4 and 5) compare to electron-rich aryl group (entry 2). However, no significant
effect of substitution in 6-substituted indanones was observed. The byproduct n-butyl
esters were also isolated in moderate yield (data not shown).
Conclusions
In conclusion, air oxidative fragmentation of 2-aryl-1-tetralones allows a concise and
novel synthesis of 2-benzo yl-1-indanones and 1-indanone in overall two and three
steps respectively with moderate to good yield. The ring contraction thus achieved could
be a useful strategy in the synthesis of complex molecules.

4
A. KUMARI ET AL.
Table 2. 1-Indanones from 2-benzoyl-1-indanones.
O
O
R
O
5
mol% In(Otf)3
R
n
n-butanol, reflux
+ ArCOO Bu
Ar
6
7, R= H
8
9
, R= OMe
, R= F
a
entry
Substrate
time
Products (yield in %)
1
2
3
4
5
6
7
8
6a
6b
6c
6d
6e
6f
6 h
6 h
12 h
6 h
4 h
6 h
6 h
6 h
7 (86%)
7 (88%)
7 (85%)
7 (90%)
7 (86%)
8 (92%)
8 (93%)
9 (81%)
6g
6h
All the reactions were run with 0.05 M concentration of the 6 in n-butanol.
a
yields reported are isolated yields.
Experimental procedures
General procedure for the synthesis of 2-hydroxyarylidene-1-indanones
(2-benzoyl-1-indanones) 3a, 6a–h
To a solution of Methyl-2-(3-oxo-3-aryl) benzoates (1.00 mmol) in dry THF (20 ml) in a
t
round bottom flask was added KO Bu (130 mg, 1.16 mmol) at room temperature. The
reaction flask was then fitted with septa and argon filled balloon and stirred for
1
0 minutes. The reaction was then quenched with saturated NH Cl solution (10 ml) and
4
extracted with ethyl acetate (2 ꢀ 50 ml). The combined organic layer was washed with
brine (10 ml) and dried over anhydrous sodium sulfate. Evaporation of solvent gave
crude product which upon column chromatography with 5% EtOAc/Hexane gave 2-
hydroxyarylidene-1-indanones (2-benzoyl-1-indanones).
5
a
2
-(Hydroxy-phenyl-methylene)-indan-1-one 3a (known) Yield 208 mg (88%); light
ꢁ
1
yellow solid; R ¼ 0.40 (10% EtOAc/hexane); mp. 92 C; H NMR (300 MHz, CDCl ) d
f
3
1
5.06 (1H,br), 7.92–7.98 (2H, m), 7.90 (1H, d, J ¼ 7.6 Hz), 7.60–7.45 (5H, m), 7.44 (1H,
13
dd, J ¼ 7.6 Hz, 7.6 Hz), 3.94 (2H, s); C NMR (75 MHz, CDCl ) d 195.9, 171.0, 148.7,
3
1
38.1, 135.0, 133.5, 131.4, 128.8, 128.3, 127.6, 125.7, 123.6, 109.6, 32.4.
General retro-Claisen reaction procedure for synthesis of 1-indanones
To a solution of 2-hydroxyarylidene-1-indanones (0.50 mmol) in n-butanol (10 ml) was
added In(OTf) (15 mg, 0.027 mmol) and the reaction was refluxed until the starting
3
material is consumed as observed by TLC. Then water (5.0 ml) was added to the reac-
tion followed by extraction with ethyl acetate (2 ꢀ 50 ml). The combined organic layer
was washed with brine (10 ml) and dried over anhydrous sodium sulfate. Evaporation
of solvent gave crude product which upon column chromatography with 5% EtOAc/
Hexane gave 1-indanones.

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1
1
-Indanone 7. H NMR (300 MHz, CDCl ) d 7.76 (1H, dd, J ¼ 7.5 Hz), 7.59 (1H, td,
3
J ¼ 7.5 Hz, 1.2 Hz), 7.48 (1H, td, J ¼ 7.5 Hz, 0.9 Hz), 7. 37 (1H, td, J ¼ 7.5 Hz, 0.9 Hz),
.15 (2H, dd, J ¼ 6.0 Hz, 6.0 Hz), 2.66–2.74 (2H, m).
3
1
13
General Information, experimental, analytical data, H, C NMR spectra and character-
ization data of all the synthesized compounds are available as Supporting Information.
Acknowledgments
The authors thank sophisticated analytical instrumentation facility (SAIF), CDRI, Lucknow, India
for NMR and HRMS analysis.
Funding
Financial supports from University Grant Commission (UGC), India [No. F.4-5(108-FRP)/2014,
BSR] and Department of Science and Technology (DST), India [YSS/2015/000356] are gratefully
acknowledged.
ORCID
Partha Ghosh
http://orcid.org/0000-0001-5912-660X
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1