Versatile synthesis of 3-arylindan-1-ones by palladium-catalyzed intramolecular reductive cyclization of bromochalcones

Article abstract of DOI:10.1055/s-2004-834929

We have developed a novel and versatile synthesis of racemic 3-arylindan-1-ones by palladium-catalyzed intramolecular reductive cyclization of bromochalcones. This method is especially attractive because it avoids strong acidic conditions and consequently a larger number of sensitive functional groups are accepted during synthesis compared with existing methods.

Full text of DOI:10.1055/s-2004-834929

PAPER
291
Versatile Synthesis of 3-Arylindan-1-ones by Palladium-Catalyzed Intramole-
cular Reductive Cyclization of Bromochalcones
S
ynthese
s
of 3-Ary
s
lindan-1-
k
ones by Intramolec
P
ula
r
C
yclizatio
ü
n
of Bromo
s
chalconeschl,*a Hans Christian Rudbeck,b André Faldt,b Allesia Confante,b Jan Kehlera
a
Medicinial Chemistry Research, H. Lundbeck A/S Ottiliavej 9, 2500, Denmark
Fax +4536301385; E-mail: askp@lundbeck.com
b
Process Research, H. Lundbeck A/S Ottiliavej 9, 2500, Denmark
Received 5 July 2004; revised 22 September 2004
Prominent examples are the antidepressant indatraline
(2),1 the antipsychotic tefludazine (3),2 the drug toltero-
dine (4),3 and many others.3–8 Furthermore, 3-aryl-1-in-
danones can also be used directly as anti-inflammatories,
Abstract: We have developed a novel and versatile synthesis of ra-
cemic 3-arylindan-1-ones by palladium-catalyzed intramolecular
reductive cyclization of bromochalcones. This method is especially
attractive because it avoids strong acidic conditions and conse-
quently a larger number of sensitive functional groups are accepted antipyretics or analgesics.9 Previously, 4 different routes
during synthesis compared with existing methods.
to 3-arylindan-1-ones have mainly been applied
(Scheme 1).10
Key words: 3-arylindan-1-ones, palladium, reductive cyclization,
chalcone, intramolecular
The routes A–C (Scheme 1) all utilize intramolecular
electrophilic aromatic substitution under rather harsh and
strongly acidic conditions from 3,3-diphenylpropionic ac-
ids (5A), 3,3-diphenylpropionyl chlorides (5B) and 1,3-
diphenylpropenones (chalcones, 6), respectively. Even in
the versatile ‘enamine route’ (Route D), where a methyl 3-
3-Arylindan-1-ones 1 (Figure 1) are versatile key inter-
mediates in the syntheses of a number of biologically ac-
tive compounds.
Figure 1 A number of biologically active compounds synthesized via 3-arylindan-1-ones.
Scheme 1 The four previously used synthetic routes A–D to 3-arylindan-1-ones.
SYNTHESIS 2005, No. 2, pp 0291–0295
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x
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Advanced online publication: 24.11.2004
DOI: 10.1055/s-2004-834929; Art ID: Z13304SS
© Georg Thieme Verlag Stuttgart · New York

292
A. Püschl et al.
PAPER
amino-1-phenyl-1-cyano-1H-indene-2-carboxylate is as-
sembled by nucleophilic aromatic substitution of an aryl
acetonitrile on an ortho-halogen-substituted cyano aro-
mate followed by alkylation with methyl chloroacetate
and subsequent intramolecular Dieckmann-type reaction
to the enamine 7, the final 3-arylindan-1-ones are ob-
tained only after heating under strongly acidic conditions.
Recently, a stereoselective synthesis of an (S)-3-arylin-
dan-1-one 1a from a 3-arylinden-1-one 9a was described
by Clark et al. via stereoselective reduction of the interme-
diate keto group in 9a and subsequent base-induced ste-
reoselective sigmatropic hydrogen rearrangement of the
allylic alcohol 10a (Scheme 2).6a Recently, Clark et al.
also described a stereoselective synthesis of (S)-3-arylin-
dan-1-one 1a from 3-arylinden-1-one 9a by enantioselec-
tive reduction of the intermediate alkene moeity in 9a.6b
Although the two different stereoselective syntheses de-
scribed by Clark et al. are very elegant, they have only
been shown to work with electron-donating aromatic sub-
stituents.
Scheme 3 Synthesis of 2¢-bromochalcones 8a–j and the subsequent
competing palladium-catalyzed Heck and hydroarylation reactions.
Several reports in the literature have dealt with the syn-
thetic challenge of intermolecular palladium-catalyzed
hydroarylation reactions of a,b-unsaturated carbonyl
compounds and aryl halides (formal conjugate Michael
addition).13 It is apparent from these literature reports, that
there is generally a competition between vinylic substitu-
tion resulting in the Heck reaction and hydroarylation re-
sulting in the conjugate addition. When translating this
into the indane-based substrates, it corresponds to a com-
petition between formation of products 3-arylinden-1-one
9 (Heck product) and 3-arylindan-1-one 1 (hydroarylation
product). We observed that we could push the balance to-
wards the hydroarylated conjugate addition product 1 as
the main product when using an organic base, e.g. trieth-
ylamine as opposed to an inorganic base, e.g. K2CO3. Pre-
sumably, triethylamine acts here as a hydride source as is
well known for Pd-catalyzed reactions.13 From earlier re-
ports it appears that the balance between Heck and hy-
droarylation depends on an intriguing combination of
steric, electronic and medium effects.14 Realizing this, we
decided to approach the problem by multivariate analysis.
We used the chalcone 8b derived from 4-fluorobenzalde-
hyde as a substrate because electron-deficient olefins are
known to be the most difficult substrates. When using
electron-deficient chalcones, we generally observed as the
main product the dehalogenated reduced ketone 11
(Scheme 4). Hence, we reasoned that if we could optimize
the reaction with the difficult electron-withdrawing fluoro
substituent, we would expect the reaction to work also
with more ‘easy’ substrates. We used DoE (modde 6.0) to
design 60 experiments, which were carried out on a 1
mmol scale and analyzed by GC-MS. In these experi-
ments triethylamine was used as the only base and di-
Scheme 2 The recently described stereoselective synthesis of (S)-3-
arylindan-1-one 1a.
Furthermore, the methods described by Clark et al. only
give access to the (S)-3-arylindan-1-one contrary to many
of the CNS active 3-arylindanes which posses the (R)-3-
aryl configuration.4,11,12 The indenone 9a was synthesized
by Clark et al. from 2¢-bromochalcone 8a by an intramo-
lecular Heck reaction.6a During our work on the syntheses
of CNS-active compounds like 2 and 3 we attempted the
analogous Heck-reaction, but besides the expected inde-
none 9 (Scheme 3) we observed also small and variable
amounts of the reduced racemic indanone 1.
In order to avoid the two-step cyclization and reduction
from 8 over 9, we decided to try to develop a direct in-
danone synthesis from the 2¢-bromochalcone 8. The 2¢-
bromochalcones 8b–j are easily available by condensing
2¢-bromoacetophenone with various substituted benzalde-
hydes under basic conditions.
Synthesis 2005, No. 2, 291–295 © Thieme Stuttgart · New York

PAPER
Syntheses of 3-Arylindan-1-ones by Intramolecular Cyclization of Bromochalcones
293
methylacetamide (DMA) was used as the solvent. Various
Pd sources [Pallacycle, PdCl2, Pd(dppf)2, Pd(OAc)2,
Pd(PPh3)2Cl2, POPd1, POPd, PdCl2MeCN2, Pd-103 and
PD-dba] combined with different phosphine ligands
[none, PPh3, P(o-Tol)3, P(tert-Bu)3, P(furfuryl)3 and
P(OPh)3] were screened. The semi-optimized procedure
obtained this way, was: Pd(PPh3)2Cl2 (1 mol%), DMA as
solvent (0.1 M), triethylamine (2 equiv) as base and a tem-
perature of 140 °C. However, when these reaction condi-
tions were used to try to ring-close the chalcone derived
from 3,4-dichlorobenzaldehyde (8e), we surprisingly ob-
served that no product was formed. A closer inspection of
the reaction set-up revealed, that the most likely cause was
that triethylamine (bp 89 °C) was not efficiently refluxed
back into the reaction mixture. We therefore decided to
screen a number of higher boiling amines. The two best
turned out to be tributylamine (NBu3) and N,N-dimethyl-
cyclohexylamine. Since the latter performed slightly bet-
ter, this was chosen as the preferred base. Furthermore, it
was found that DMF and DMA performed equally well
and since DMF is easier to remove by evaporation, DMF
was chosen as the preferred solvent. Finally the tempera-
ture was increased to 155 °C in order to speed up the reac-
tion. Furthermore, we also investigated the effect of the
type of halogen used and observed no difference in cy-
clization efficiency using either 2¢-bromo- or 2¢-iodochal-
cone. Thus, the chalcone derived from condensing 2¢-
iodoactophenone to 4-fluorobenzaldehyde gave the same
purified yield of indanone 8b as using 2¢-bromoacetophe-
none (69% versus 72%). The optimized procedure ob-
tained this way (Method A) was: Pd(PPh3)2Cl2 (1 mol%),
DMF as solvent (0.5 M), N,N-dimethylcyclohexylamine
(2 equiv) as base and a temperature of 155 °C. The isolat-
ed yields using Method A were satisfactory ranging from
58–83% (Table 1). We were able to further optimize the
reaction conditions by using microwave conditions
(Method B). Thereby the reaction time was decreased
from approximately 1–2 hours to 15 minutes. Generally,
we did not observe any major differences in the yields be-
tween the two heating methods.
Scheme 4 Suggested mechanism for the catalytic Pd cycle leading
to the Heck product 9 or hydroarylation product 1. A compound with
reduced double bond and reduced bromine 11 have also been obser-
ved when R = electron-withdrawing or ortho-substituents.
instead of 1 h). We therefore believe that two different re-
action paths are possible, one leading to the indenone 9b
and the other to the indanone 1b. Notably, the ring closure
is formally a 5-endo-trig cyclization, which according to
Baldwin is disfavored. Based on analogy with the inter-
molecular reaction,13 we therefore suggest the mechanism
outlined in Scheme 4. After oxidative insertion of the aryl
halide to palladium(0) resulting in the complex 12 fol-
lowed by double bond insertion, the adduct 13 normally
would have been expected to undergo reductive elimina-
tion with formation of the styrene 9 according to the well
known Heck reaction. However, because of the nature of
the syn addition to the double bond, the resulting cis-com-
plex 13 does not readily undergo b-elimination. This is
because the rigid trans configuration of the b-hydrogen
and palladium atom hinders elimination of the hydropal-
ladium halide. Therefore, the complex 13 can be forced to
undergo a Ca-Pd heterolytic bond cleavage followed by
rapid protonation of the anionic moiety 14 by trialkylam-
monium bromide resulting in the racemic indanone 1.
This suggested mechanism is in line with what has been
suggested for palladium-catalyzed intermolecular conju-
gate addition of aryl iodides with a,b-unsaturated ketones
by Cacchi et al.13b In order not to terminate the catalytic
cycle, the reduction of palladium(II) to palladium(0) is
achieved by the tertiary amine as described in the litera-
ture.13 Hence, the use of an organic amine base is crucial
in order to direct the reaction towards conjugate addition
since the amine serves both as a reducing agent towards
The yields using Method B were satisfactory ranging from
33–83% (Table 1). Generally, we observed a very good
functional group compatibility accepting both electron-
withdrawing and electron-donating substituents. In-
danones incorporating chloro (1e), amide (1g), ester (1h),
and nitrile (1i) functional groups were all formed in ac-
ceptable yields. Only 1j (containing the nitro group) could
not be prepared by these methods. The method is quite
sensitive to steric effects. This is seen for the 2-methoxy-
chalcone 8f which is cyclized to the indanone 1f in only
33% yield – the major side product being the partially re-
duced ketone 11 (compare entry 3 and 5, Method B).
During the reaction the indenone 9b seemed to be an in-
termediate, as judged by LC-MS. It was believed then that
9b is reduced to the indanone 1b. However, when Method
A conditions were applied to the indenone 9b (synthe-
sized from 8b using a slightly modified method as de-
scribed in Ref.6), the conversion to 1b was very slow (6 h
Synthesis 2005, No. 2, 291–295 © Thieme Stuttgart · New York

294
A. Püschl et al.
PAPER
Table 1 Reductive Cyclization of Bromochalcones 8b–j
R
Reactant
(Chalcone)
Product
(Indanone)
Conventional Heating
(Method A)a
Microwave Heating
(Method B)
78 (73)c
66 (72)c
87 (82)c
83 (58)c
33
4-F
8b
8c
8d
8e
8f
1b
1c
1d
1e
1f
72 (43)b
65 (38)b
83 (65)b
58 (0)b
n.d.
H
4-OMe
3,4-Cl2
2-OMe
4-NHCOCH3
4-CO2Et
4-CN
8g
8h
8i
1g
1h
1i
n.d.
45
n.d.
57
n.d.
64
4-NO2
8j
1j
n.d.
0
a n.d. = not detected.
b Numbers in parentheses indicate yields with Et3N as base instead of N,N-dimethylcyclohexylamine.
c 5 mol% (PPh3)2PdCl2 catalyst was used (instead of 1 mol%).
gel 60 (0.04–0.063 mm). NMR analysis was performed on a
BRUKER instrument operating at 500.1 MHz (1H NMR) and 125.8
MHz (13C NMR). Samples were dissolved in CDCl3 and peaks were
referenced to TMS. Chemicals and solvents were bought from Al-
drich.
palladium(II) and the corresponding ammonium ion
serves as the hydrogen source. This explanation is also
consistent with the observation that the Heck reaction path
is dominant when an inorganic base like potassium car-
bonate is used.
3-Arylindan-1-ones 1; General Procedures
Preliminary attempts towards a stereoselective synthesis
using chiral phosphine ligands were also carried out.
Probably because of the stringent requirement of the reac-
tion conditions (most notably the high temperature
155 °C), these attempts have so far not been successful. In
these preliminary experiments only (R)- and (S)-BINAP
seems to be able to catalyze the ring closure properly,
whereas (R)-Tol-Binap, (R,R)-Me-DuPhos, and (R)-Pha-
Method A (Conventional Heating): This method is identical to
method B, except that conventional heating was used for 2 h instead
of microwave heating.
Method
B (Microwave Heating): The chalcone (5 mmol),
(Ph3P)2PdCl2 (35 mg, 0.05 mmol) and N,N-dimethylcyclohexyl-
amine (1.27 g, 10.0 mmol) were dissolved in DMF (10 mL). The re-
action container was fitted with a normal reflux condenser and an
argon atmosphere was established. Microwave irradiation was used
nephos are much less efficient. Unfortunately, no stereo- to increase the temperature to 160 °C in 3 min and this temperature
was maintained for a further 12 min. The solvent was evaporated off
selectivity has so far been detected. Furthermore, the
and the residue was taken up in EtOAc (100 mL) and aq 2 M HCl
stereochemical outcome might depend strongly on the
(50 mL). The phases were separated and the organic phase was
substrate and especially the aromatic substitution pattern
washed with aq 2 M HCl (50 mL), brine and dried (Na2SO4). The
possibly preventing development of a general procedure.
crude product was purified by chromatography using a gradient of
EtOAc in heptane.
In conclusion we have developed a simple non-moisture
sensitive and rapid synthesis of racemic 3-arylindan-1-
ones. This method tolerates acid sensitive groups and re-
duction sensitive groups like the methoxy, nitrile and ester
groups, which are partly degraded when using the more
harsh acidic procedures A–D. Furthermore, the starting
materials (chalcones) are easy to synthesize from com-
mercially available aryl aldehydes. The major limitation is
that nucleophilic moieties (e.g. pyridine) are not tolerated
in the reactants (chalcones) since they would be prone to
self-condensation by 1,4-addition to these enones.
3-(4-Fluorophenyl)indan-1-one (1b)
Mp 119–120 °C (Lit.11 mp 121–122 °C).
1H NMR: d = 7.70 (d, 1 H), 7.65 (t, 1 H), 7.46 (t, 1 H), 7.25 (m, 3
H), 7.15 (t, 2 H), 4.70 (m, 1 H), 3.22 (dd, 1 H), 2.60 (dd, 1 H).
13C NMR: d = 205.3, 162.3, 160.4, 158.1, 140.3, 136.5, 135.5,
129.9, 128.3, 127.1, 123.1, 115.9, 46.4, 43.1.
Anal. Calcd for C15H11FO: C, 79.63; H, 4.90. Found: C, 79.70; H,
5.06.
3-Phenylindan-1-one (1c)
Mp 76–78 °C (Lit.15 mp 76–77 °C).
1H NMR: d = 7.71 (d, 1 H), 7.62 (t, 1 H), 7.48 (t, 1 H), 7.35–7.15
Reactions were carried out in a Carousel reaction station (from
Radley discovery) in 30 mL reaction tubes under argon. Microwave
reactions were carried out in a single mode cavity (from Prolabo)
operating at 2450 MHz under argon but not under high pressure
(open system). Flash chromatography was carried out using silica
(m, 6 H), 4.68 (m, 1 H), 3.24 (dd, 1 H), 2.63 (dd, 1 H).
13C NMR: d = 205.5, 158.3, 144.2, 136.5, 135.5, 129.1, 128.2,
127.9, 127.1, 127.0, 123.1, 46.4, 43.9.
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Syntheses of 3-Arylindan-1-ones by Intramolecular Cyclization of Bromochalcones
295
Anal. Calcd for C15H12O: C, 86.51; H, 5.81. Found: C, 86.53; H,
5.86.
Anal. Calcd for C16H11NO: C, 82.38; H, 4.76; N, 6.01 Found: C,
82.37; H, 4.82; N, 5.89.
3-(4-Methoxyphenyl)indan-1-one (1d)
Mp 71–73 °C (Lit.16 mp 72–73 °C).
References
1H NMR: d = 7.71 (d, 1 H), 7.65 (t, 1 H), 7.46 (t, 1 H), 7.25 (d, 1 H),
7.10 (d, 2 H), 6.90 (d, 2 H), 4.62 (m, 1 H), 3.72 (s, 3 H), 3.20 (dd, 1
H), 2.57 (dd, 1 H).
13C NMR: d = 205.7, 158.7, 158.4, 136.4, 136.0, 135.5, 128.9,
128.1, 127.1, 123.0, 114.5, 55.4, 46.6, 43.1.
(1) Bogeso, K. P.; Christensen, A. V.; Hyttel, J.; Liljefors, T. J.
Med. Chem. 1985, 28, 1817.
(2) Bogeso, K. P.; Arnt, J.; Frederiksen, K.; Hansen, H. O.;
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(3) Andersson, P. G.; Hedberg, C. Pharmacia AB, Swed., PCT
Int. Appl. WO 0149649 A1, 2001; Chem. Abstr. 2001, 135,
92442.
Anal. Calcd for C16H14O2: C, 80.35; H, 5.92. Found: C, 80.68; H,
6.01.
(4) Boegesoe, K. P.; Arnt, J.; Hyttel, J.; Pedersen, H. J. Med.
Chem. 1993, 36, 2761.
3-(3,4-Dichlorophenyl)indan-1-one (1e)
(5) Guillon, J.; Dallemagne, P.; Leger, J.-M.; Sopkova, J.; Bovy,
P. R.; Jarry, C.; Rault, S. Bioorg. Med. Chem. 2002, 10,
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(6) (a) Clark, W. M.; Tickner-Eldridge, A. M.; Huang, G. K.;
Pridgen, L. N.; Olsen, M. A.; Mills, R. J.; Lantos, I.; Baine,
N. H. J. Am. Chem. Soc. 1998, 120, 4550. (b) Clark, W. M.;
Kassick, A. J.; Plotkin, M. A.; Eldridge, A. M.; Lantos, I.;
Baine, N. H. Org. Lett. 1999, 1, 1839.
Mp 110–112 °C (Lit.11 mp 113–115 °C).
1H NMR: d = 7.71 (d, 1 H), 7.66 (t, 1 H), 7.58 (d, 1 H), 7.52 (m, 2
H), 7.31 (d, 1 H), 7.18 (d, 1 H), 4.72 (m, 1 H), 3.22 (dd, 1 H), 2.65
(dd, 1 H).
13C NMR: d = 204.9, 158.2, 145.3, 136.6, 135.6, 131.6, 131.3,
130.2, 129.7, 128.5, 128.4, 127.1, 123.3, 45.9, 42.9.
Anal. Calcd for C15H10Cl2O: C, 65.01; H, 3.64, Found: C, 65.34; H,
3.82.
(7) Huhtala, P.; Arto, K.; Antti, H.; Jyrki, L.; Arja, K.; Raimo,
V. Orion Corporation, Finland, PCT Int. Appl. WO 0151472
A1, 2001; Chem. Abstr. 2001, 135, 107327.
3-(2-Methoxyphenyl)indan-1-one (1f)
Mp 100–101 °C.
(8) Patra, A.; Misra, S. K. Indian J. Chem., Sect. B: Org. Chem.
Incl. Med. Chem. 1990, 29, 66.
1H NMR (CDCl3): d = 7.79 (d, 1 H), 7.54 (t, 1 H), 7.38 (t, 1 H), 7.30
(t, 1 H), 7.22 (t, 1 H), 6.94 (d, 1 H), 6.90 (m, 2 H), 4.89 (m, 1 H),
3.73 (s, 3 H), 3.15 (dd, 1 H), 2.68 (dd, 1 H).
13C NMR (CDCl3): d = 207.1, 158.3, 157.7, 137.5, 135.1, 132.1,
128.8, 128.5, 127.9, 127.0, 123.7, 121.1, 111.3, 55.7, 45.6, 39.5.
(9) (a) Rufer, C.; Boettcher, I. Schering A.-G. Germany, DE
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(b) Williamson, W. R. N. Lilly Industries Ltd., UK, GB
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(10) (a) Route A: Kofron, W. G. Geigy Chemical Corp., US
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Froimowitz, M.; Wu, K.-M.; Moussa, A.; Haidar, R. M.;
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43, 4981. (e) See also: Smonou, I.; Orfanopoulos, M. Synth.
Commun. 1990, 20, 1387; and references 1-3 cited therein.
(f) Route C: Dupin, J. F. E.; Chenault, J. Heterocycles 1983,
20, 2401. (g) See also: Allen, J. M.; Johnston, K. M.; Jones,
J. F.; Shotter, R. G. Tetrahedron 1977, 33, 2083. (h) See
also: McDonald, E.; Smith, P. J. Chem. Soc., Perkin Trans.
1 1980, 837. (i) intermolecular Version: Shotter, R. G.;
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(j) See also: Kemp, W.; Spanswick, J. J. Chem. Soc., Perkin
Trans. 1 1972, 151. (k) See also: Merchant, J. R.; Kamath,
M. S.; Dike, S. Y. J. Chem. Soc., Perkin Trans. 1 1977,
2089. (l) Route D: Sommer, M. B.; Begtrup, M.; Boegesoe,
K. P. J. Org. Chem. 1990, 55, 4822.
(11) Boegesoe, K. P. J. Med. Chem. 1983, 26, 935.
(12) Liljefors, T.; Boegesoe, K. P. J. Med. Chem. 1988, 31, 306.
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(14) (a) For a recent review, see: Catellani, M. Synlett 2003, 298.
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1999, 345; and reference 9 cited therein.
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E.; Hunt, J. S. J. Chem. Soc. 1956, 2928.
Anal. Calcd for C16H14O2: C, 80.65; H, 5.92. Found: C, 80.19; H,
5.97.
3-[4-(Acetylamino)phenyl]indan-1-one (1g)
Mp 160–161 °C.
1H NMR (CDCl3): d = 7.78 (m, 2 H), 7.54 (t, 1 H), 7.46 (d, 2 H),
7.40 (t, 1 H), 7.24 (t, 1 H), 7.06 (d, 2 H), 4.54 (m, 1 H), 3.21 (dd, 1
H), 2.63 (dd, 1 H), 2.15 (s, 3 H).
13C NMR (CDCl3): d = 206.6, 169.0, 158.3, 139.9, 137.3, 137.0,
135.6, 128.8, 128.5, 128.3, 127.3, 123.8, 120.9, 47.2, 44.3, 24.9.
Anal. Calcd for C17H15NO2: C, 76.96; H, 5.70; N, 5.28. Found: C,
76.56; H, 5.82; N, 5.18.
4-(3-Oxoindan-1-yl)benzoic Acid Ethyl Ester (1h)
Mp 113–114 °C.
1H NMR (CDCl3): d = 7.98 (d, 2 H), 7.83 (d, 1 H), 7.58 (t, 1 H), 7.46
(t, 1 H), 7.25 (d, 1 H), 7.21 (d, 2 H), 4.64 (m, 1 H), 4.37 (q, 2 H),
3.24 (dd, 1 H), 2.68 (dd, 1 H), 1.39 (t, 3 H).
13C NMR (CDCl3): d = 205.7, 166.6, 157.5, 149.2, 137.2, 135.6,
130.6, 129.8, 128.6, 128.0, 127.2, 124.0, 61.4, 46.9, 44.7, 14.7.
Anal. Calcd for C18H16O3: C, 77.12; H, 5.75. Found: C, 77.00; H,
5.90.
3-(4-Cyanophenyl)indan-1-one (1i)
1H NMR (CDCl3): d = 7.83 (d, 1 H), 7.60 (m, 3 H), 7.47 (t, 1 H),
7.25 (m, 3 H), 4.65 (m, 1 H), 3.25 (dd, 1 H), 2.64 (dd, 1 H).
13C NMR (CDCl3): d = 204.7, 156.3, 149.2, 136.8, 135.4, 132.8,
128.5, 126.7, 123.8, 118.6, 111.1, 46.3.
Synthesis 2005, No. 2, 291–295 © Thieme Stuttgart · New York