Superacid-promoted hydroxyalkylation of 1,2-indandiones

Article abstract of DOI:10.1080/00397911.2012.693239

1,2-Indandione reacts efficiently with arenes to give 2,2-diaryl-1- indanones by the hydroxyalkylation reaction. The Bronsted superacid CF₃SO₃H (triflic acid) is an effective catalyst for these condensation reactions. The requisite 1

Full text of DOI:10.1080/00397911.2012.693239

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Superacid-Promoted Hydroxyalkylation
of 1,2-Indandiones
Adam F. Tracy a , Matthew P. Abbott a & Douglas A. Klumpp a
a Department of Chemistry and Biochemistry , Northern Illinois
University , DeKalb , Illinois , USA
Accepted author version posted online: 05 Mar 2013.Published
online: 03 Jun 2013.
To cite this article: Adam F. Tracy , Matthew P. Abbott & Douglas A. Klumpp (2013): Superacid-
Promoted Hydroxyalkylation of 1,2-Indandiones, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 43:16, 2171-2177
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Synthetic Communications1, 43: 2171–2177, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2012.693239
SUPERACID-PROMOTED HYDROXYALKYLATION OF
1,2-INDANDIONES
Adam F. Tracy, Matthew P. Abbott, and Douglas A. Klumpp
Department of Chemistry and Biochemistry, Northern Illinois University,
DeKalb, Illinois, USA
GRAPHICAL ABSTRACT
Abstract 1,2-Indandione reacts efficiently with arenes to give 2,2-diaryl-1-indanones by the
hydroxyalkylation reaction. The Brønsted superacid CF3SO3H (triflic acid) is an effective
catalyst for these condensation reactions. The requisite 1,2-indandiones were prepared from
the 1-indanones.
Keywords Condensation; Friedel–Crafts; indanone; superacid
INTRODUCTION
The hydroxyalkylation reaction is an acid-catalyzed condensation of aldehydes
and ketones with arenes.[1] It is a common industrial reaction, as it is used to prepare
feedstock chemicals, aromatic monomers, and condensation polymers. In 1995,
Yamazaki and coworkers described a superacid-promoted hydroxyalkylation reac-
tion of 2,3-butanedione (1) to give the condensation product 3 in excellent yield
[Eq. (1)].[2] The diprotonated superelectrophile (2) was proposed as an intermediate
in the reaction.[3] Several other recent articles have described superacid-promoted
hydroxyalkylation reactions with 1,2-dicarbonyl compounds.[4] For example, pro-
ducts 5–7 are prepared from the respective condensation reactions of acenaphthene-
quinone, isatin, and parabanic acid, with benzene and triflic acid.
Received May 3, 2012.
Address correspondence to Douglas A. Klumpp, Department of Chemistry and Biochemistry,
Northern Illinois University, Dekalb, IL 60115, USA. E-mail: dklumppe@niu.edu
2171

2172
A. F. TRACY, M. P. ABBOTT, AND D. A. KLUMPP
These types of superacid-promoted reactions have also recently been shown to
be useful in polymerization chemistry.[5] In the following article, we describe
superacid-promoted hydroxyalkylation reactions of 1,2-indandione and substituted
derivatives. The conversions lead to 2,2-diaryl-1-indanone products and a mech-
anism is proposed involving a deprotonated superelectrophilic intermediate.
RESULTS AND DISCUSSION
Although 1,2-indandione (7) is available from commercial suppliers, substi-
tuted derivatives may be prepared from the 1-indanones.[6] Thus, 4-bromoindanone
was converted to the oxime 8 by reaction with isoamylnitrite, and hydrolysis liber-
ates the substituted 1,2-indandione 9 [Eq. (2)]. Similar reactions were done with
5-methoxyindanone and 4-methoxyindanone to prepare the respective 1,2-diketones.
We also sought to compare the reactions of 2,2-dichloro-1-indanones (10) and
2,2-dimethoxy-1-indanones (11) as possible substrates in the synthesis.
The desired compounds were prepared by chlorination of the 1-indanone
[Eq. (3)] and by acetalization of 1,2-indandione [Eq. (4)].[6,7]
With 1,2-indandione, the condensation product (12) is formed in 81% yield by
reaction at the 2-position (Scheme 1). The identity of 12 was verified by comparison
with an authentic sample of 12 (prepared from a different approach[8]), and it was

PREPARATION OF 2,2-DIARYL-1-INDANONES
2173
Scheme 1. Synthetic approaches to 2,2-diphenyl-1-indanone (12).
clear that condensation occurs exclusively at the 2-carbonyl group. The regiochem-
istry of condensation was also confirmed by x-ray crystallographic analysis. During
the course of our studies, we found that some 1,2-indandiones were prone to decom-
pose during storage. This prompted us to explore the possibility of protecting the
diketone as the dimethoxyacetal. Although the acetal substrates were easily prepared
and indefinitely stable, the condensation reaction from 11 provided compound 12 in
a disappointing 43% yield. As an alternative strategy from the dichloride, compound
10 gave product 12 in a fair yield of 61%.
Using substituted arenes, the condensation reactions provide the products in
good yields. Thus, reaction of 7 with triflic acid and fluorobenzene or toluene gives
the respective products (13 and 14) in 85% and 67% yields (Scheme 2). The electro-
philic aromatic substitution occurs with excellent regioselectivity, as gas chromato-
graphy (GC) and NMR analysis shows at least a 20:1 para=ortho ratio. This is a
trend previously observed with other 1,2-dicarbonyl systems—very good regioselec-
tivity is seen in the condensation reactions with alkylbenzenes and monohalogenated
benzenes.[4] We also obtained the condensation product from 1,3-dichlorobenzene
(15), although the yield is considerably lower. In some cases, minor amounts of
the intermediate product inden-1-ones (i.e., 16) could also be detected by GCMS
analysis. Finally, substituted 1,2-indandiones were also prepared and reacted with
Scheme 2. Products (13–15) from the reaction of 1,2-indandione.

2174
A. F. TRACY, M. P. ABBOTT, AND D. A. KLUMPP
Scheme 3. Proposed reaction mechanism with DFT calculated relative energies of monocations 20 and 21.
CF3SO3H and benzene. 6-Methoxy and 5-methoxy-substituted1,2-indandiones pro-
vide condensation products 17 and 18, respectively. Similarly, 4-bromo-1,2-indan-
dione gives the condensation product 19 in excellent yield from CF3SO3H.
Hydroxyalkylation reactions generally occur via carboxonium intermediates
by protonation of aldehyde or ketone carbonyl groups.[1] In the case of 1,2-indan-
dione (7), initial protonation could occur at either the 1- or 2-carbonyl group
(Scheme 3). Density functional theory (DFT) calculations [B3LYP 6-311 G (d,p)
level] indicate that protonation at the 1-carbonyl group is significantly favored.[9]
However, condensation occurs at the 2-carbonyl. Benzene (and other arenes) are
weak nucleophiles, and consequently, direct attack of benzene at the 2-carbonyl
group of 21 is not considered a likely reaction step. Two plausible mechanisms
can be suggested. A second protonation of 21 leads to superelectrophile 22 and reac-
tion with benzene then occurs to provide adduct 23. This mechanistic path could also
involve only a partially diprotonated species where the 2-carbonyl group is forming a
strong hydrogen bond to the superacid. Alternatively, reaction through the mono-
protonated species (20) could directly give 23 and further reaction steps then lead
to product 12.
CONCLUSION
Using the Brønsted superacid CF3SO3H, 1,2-indandiones form condensation
products with benzene and substituted arenes. The chemistry provides easy access

PREPARATION OF 2,2-DIARYL-1-INDANONES
2175
Table 1. Analytical data for condensation products 13–15 and 17–19
Mass spectrum
(low res.; EI)
Mass spectrum
(high res.; EI)
No. Mp (ꢀC)
1H NMR
13C NMR
13 143–145 CDCl3, d: 3.91 (s, 2H), CDCl3, d: 44.8, 61.5,
320 (Mþ), 270, Calcd. for
225, 196, 190 C21H14OF2,
6.98 (m, 4H), 7.25–
7.31 (m, 4H), 7.44–
7.47 (m, 1H), 7.56 (d,
1H, J ¼ 7.3 Hz), 7.68–
7.71 (m, 1H), 7.84 (d,
1H, J ¼ 7.6 Hz)
115.3 (d, JC-F
21.2 Hz), 125.3, 125.9,
128.2, 129.7 (d, JC-F
¼
320.10128;
found
320.10207
¼
7.9 Hz), 135.4, 135.6,
139.1, 151.6, 161.7 (d,
JC-F ¼ 245 Hz), 204.9
14
108–111 CDCl3, d: 2.34 (s, 6H), CDCl3, d: 20.9, 44.9,
312 (Mþ), 269, Calcd. for
3.92 (s, 2H), 7.11 (d,
4H, J ¼ 8.2 Hz), 7.20
(d, 4H, J ¼ 8.2 Hz),
7.41–7.44 (m, 1H),
7.53 (d, 1H,
62.2, 125.2, 125.8,
127.8, 128.0, 129.1,
135.2, 135.8, 136.3,
140.6, 152.1, 205.6
253, 220, 178
C23H20O,
312.15142;
found
312.15193
J ¼ 7.6 Hz), 7.65–7.68
(m, 1H), 7.83 (d, 1H,
J ¼ 7.6 Hz)
15
194–196 CDCl3, d: 4.21 (s, 2H), CDCl3, d: 43.8, 62.9,
424=422=420
(Mþ),
Calcd. for
C21H12OCl4,
419.96422;
found
7.08 (d, 2H,
J ¼ 8.4 Hz), 7.18 (dd,
2H, J ¼ 8.6, 2.2 Hz),
7.45–7.48 (m, 6H),
7.66–7.69 (m, 1H),
7.92 (d, 1H,
124.5, 126.2, 127.1,
128.0, 131.4, 131.8,
134.1, 134.9, 135.8,
136.3, 137.1, 152.0,
204.8
387=385, 286,
252=250, 143,
125
419.96345
J ¼ 7.4 Hz)
17
18
19
151–154 CDCl3, 300 MHz, d:
3.86 (s, 3H), 3.87 (s,
2H), 7.25–7.33 (m,
12H), 7.44 (d, 1H,
J ¼ 9.3).
CDCl3, 300 MHz, d:
44.3, 55.6, 63.6, 106.2,
124.8, 126.6, 126.7,
128.2, 129.4, 136.9,
143.6, 144.9, 159.8,
205.3
314 (Mþ), 253, Calcd. for
237, 223, 165.
C22H18O2,
314.13068;
found
314.13160
135–137 CDCl3, 300 MHz, d:
3.86 (s, 3H), 3.87 (s,
2H), 7.25–7.33 (m,
12H), 7.439 (d, 1H,
J ¼ 9.3 Hz)
CDCl3, 300 MHz, d:
44.9, 55.7, 62.9,
314 (Mþ), 285, Calcd. for
237, 223, 165
C22H18O2,
314.13068;
found
109.11, 115.9, 126.7,
126.9, 128.2, 128.4,
128.9, 143.9, 155.0,
165.9, 203.5
314.13000
114–117 CDCl3, 300 MHz, d:
3.90 (s, 1H), 7.24–7.38
(m, 11H), 7.79 (d, 1H,
J ¼ 7.5 Hz), 7.84 (dd,
CDCl3, 300 MHz, d:
45.6, 62.9, 121.4,
124.0, 127.0, 128.6,
129.8, 137.6, 138.0,
142.9, 151.7, 204.6
364=362 (Mþ), Calcd. for
284, 265, 252,
178
C21H15OBr,
362.03063;
found
362.03151
1H, J ¼ 7.8, 8.7 Hz).
to aryl-functionalized 1-indanones. Moreover, the condensation occurs with good
positional selectivity in reactions with substituted benzenes.
EXPERIMENTAL
Solvents and reagents were purchased from commercial suppliers and used
as received. The triflic acid was distilled from an Ar atmosphere prior to its use.

2176
A. F. TRACY, M. P. ABBOTT, AND D. A. KLUMPP
Compounds were purified using standard flash chromatography–grade silica gel.
Low-resolution mass spectra (LRMS) were obtained from a commercial GC instru-
ment equipped with a mass selective detector. High-resolution mass spectra (HRMS)
were obtained by an external analytical laboratory. All NMR spectra were obtained
from a Bruker Avance DRX-500 instrument.
Preparation of Condensation Products 12–15 and 17–19
The 1,2-Indandione (1 mmol) is dissolved in CH2Cl2 (5 mL), and the aromatic
compound (1 mL) is added. The vessel is purged with Ar and then triflic acid (1 mL,
11 mmol) is slowly added to the solution with stirring. After 3 h, the mixture is
poured over ice. The resulting mixture is extracted twice with chloroform, and the
organic extracts are combined. The organic solution is washed with water (2 ꢁ )
and then brine (2 ꢁ ) and dried over anhydrous sodium sulfate. Filtration and
removal of the solvent provides the crude condensation product. In some cases,
the resulting product is greater than 95% pure (GC analysis) and requires no further
purification. However, mixtures were purified by flash chromatography (hexanes–
ether).
Alternative Condensation Procedure for 12
2,2-Dichloro-1-indanone (0.15 g, 1 mmol) is dissolved in benzene (5 mL), and
anhydrous aluminum chloride (0.67 g, 5 mmol) is added. The solution is refluxed
under Ar for 4 h and then poured over ice. The resulting mixture is extracted twice
with chloroform, and the organic extracts are combined. The organic solution is
washed with water (2 ꢁ ) and then brine (2 ꢁ ), and dried over anhydrous sodium sul-
fate. Filtration and removal of the solvent provides the crude condensation product.
Compound 12 is then isolated by flash chromatography (hexanes–ether).
ACKNOWLEDGMENT
Financial support from the NIH National Institute of General Medical
Sciences (GM085736-01A1) is gratefully acknowledged.
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