Preparation of 1-indanones with conventional heating versus microwaves

Article abstract of DOI:10.1081/SCC-120013742

The acylation reactions of p-methylphenol with crotonic and 2-octenoic acids was carried out with the employment of conventional heating and irradiation by microwaves. The use of microwaves led to a significant reduction in the time of reaction from several hours to 2 min and 30-60% yield.

Full text of DOI:10.1081/SCC-120013742

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PREPARATION OF 1-INDANONES WITH CONVENTIONAL
HEATING VERSUS MICROWAVES
Erick S. da Camara e Silva a , J. D. Figueroa-Villar a & Alcino Palermo de Aguiar b
a Departamento de Engenharia Química, Instituto Militar de Engenharia, Rio de Janeiro,
22290-270, Brazil
b Departamento de Engenharia Química, Instituto Militar de Engenharia, Rio de Janeiro,
22290-270, Brazil
Version of record first published: 16 Aug 2006.
To cite this article: Erick S. da Camara e Silva, J. D. Figueroa-Villar & Alcino Palermo de Aguiar (2002): PREPARATION OF 1-
INDANONES WITH CONVENTIONAL HEATING VERSUS MICROWAVES, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 32:20, 3193-3198
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 20, pp. 3193–3198, 2002
PREPARATION OF 1-INDANONES
WITH CONVENTIONAL HEATING
VERSUS MICROWAVES
Erick S. da Camara e Silva, J. D. Figueroa-Villar,
*
and Alcino Palermo de Aguiar
Departamento de Engenharia Quımica, Instituto Militar
de Engenharia, 22290-270, Rio de Janeiro, Brazil
ABSTRACT
The acylation reactions of p-methylphenol with crotonic and
2-octenoic acids was carried out with the employment of
conventional heating and irradiation by microwaves. The use
of microwaves led to a significant reduction in the time of
reaction from several hours to 2 min and 30–60% yield
Key Words: Acylation; Indanones; Microwaves
INTRODUCTION
1-Indanone and its analogs have been demonstrated to be versatile
and useful intermediates in the preparation of different products, some of
*Corresponding author. E-mail: alcino@epq.ime.eb.br
3193
DOI: 10.1081/SCC-120013742
Copyright & 2002 by Marcel Dekker, Inc.
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3194
SILVA, FIGUEROA-VILLAR, AND AGUIAR
which have applications as pharmaceuticals, especially as analgesics[1] and
antihypertensives,[2] as well as tobacco flavoring agents.[3]
The synthesis of indanones is usually carried out by reaction of Friedel-
Crafts or Fries rearrangement using acyl chlorides or a,b-unsaturated
carboxylic acids.[4] This methodologies have some limitations, for example,
low yields,[5] use of toxic reagent and long reaction times.[6]
The objective of this work was to investigate the preparation of
1-indanones by reaction of p-methylphenol with a,b-unsaturated carboxylic
acids using conventional heating and irradiation with microwaves. The
interest in this last methodology is that it accelerates a variety of synthetic
transformations and has potential to improve reactions from an environ-
mental point of view.[7]
RESULTS AND DISCUSSION
Although different methodologies to promote acylation of aromatic
compounds are known,[8,9] we used initially the conventional procedures,[10]
that is the direct Friedel-Crafts reaction between p-methylphenol and
a,b-unsaturated carboxylic acids in presence of an appropriate Lewis acid
in a suitable solvent or the Fries rearrangement of the corresponding
O-acylated intermediate (Sch. 1). This procedure was used to prepare
1-indanones 1 and 3 in 40 and 60% yield (Table 1).
Interestingly, the o-acylphenol 2 was obtained only when the acylating
agent was crotonyl chloride. Although it is known that 2 can be obtained
from the reaction of the phenol and crotonic acid in tetrachloroethane,[10]
similar results were observed when chlorobenzene was used as solvent
(Entries 1 and 2 in Table 1).
The tests of this reaction system with longer reaction times (Entry 3 in
Table 1) led predominantly to the cyclization product 1, indicating that
compound 2 can be the intermediate in the formation of indanone 1.[11]
It was observed that, when 2-octenoic acid was used, a better yield of the
novel 1-indanone 3 was obtained (Entries 4 and 5 in Table 1).
Scheme 1. Products formed using conventional heating.

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PREPARATION OF 1-INDANONES
3195
Table 1. Preparation of 1-Indanones Using the Conventional Route
Entry
Substrate
Time (h)
Product/Yield (%)
1
2
3
4
5
Crotonic acid
Crotonic acid
Crotonic acid
2-Octenoic acid
2-Octenoic acid
5
19
24
9
1/(2)
1/(3)
1/(40)
3/(35)
3/(60)
2/(10)
2/(39)
2/(4)
Not observed
Not observed
19
Scheme 2. Production of 1-indanone with microwave.
Table 2. Preparation of 1-Indanones Using Microwaves
Entry
Substrate
Time (min)
Product/Yield (%)
1
2
Crotonic acid
2-Octenoic acid
2
2
1/45
3/33
Looking for new routes to prepare derived 1-indanones, the use of
microwave radiation was investigated as the source of the necessary reaction
activation energy.[12] In this reaction sequence (Sch. 2) the same compounds
were used ( p-methylphenol, the two a,b-unsaturated carboxylic acids and
AlCl3 in a ratio 1/1/2), but the reactions were carried out without solvent. It
was observed that the reactions were completed in a short time, as detected
by thin layer chromatography, forming the indanones 1 and 3 as the only
isolated products in 45% and 33% yields, respectively (Table 2).
EXPERIMENTAL
1H and 13C NMR spectra were recorded in CDCl3 in a Varian
Unity-300 (300 MHz 1H and 75 MHz for 13C) and a Bruker DPX 200

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3196
SILVA, FIGUEROA-VILLAR, AND AGUIAR
(200 MHz 1H and 50 MHz for 13C) spectrometers, using TMS as an
internal standard. Infrared spectra were recorded with a Nicolet Protege
460 E.S.P. All melting points are uncorrected and measured in a Fisher-
Johns apparatus. TLC analyses were carried out on precoated silica
gel aluminium plates 60 F254 (Merck). Column chromatography was
performed using Merck silica gel 60 (230–400 mesh). Microwave irradia-
tions were carried out in a commercial Panasonic model NNS59BH micro-
wave oven.
General Procedure
Reaction with conventional heating: To a stirred suspension of anhy-
drous AlCl3 (1.10 g, 8.5 mmol) in chlorobenzene (2 mL) at 30ꢀC was
slowly added a solution of p-methylphenol (0.45 mg, 4.2 mmol) and the
a,b-unsaturated carboxylic acid (4.2 mmol) in chlorobenzene (3 mL) over
a period of 20 min. During the addition, hydrogen chloride evolved
vigorously from the reaction mixture. The mixture was gradually heated
in oil bath and kept under reflux for the desired time (Table 1). Thereafter
the mixture was chilled and poured over water (1 mL) containing crushed
ice (7 g) and concentrated hydrochloric acid (17.5 mmol). The organic layer
was separated, washed with saturated bicarbonate solution and water
and dried over anhydrous magnesium sulfate. After filtration, the solvents
were removed under vacuum to afford an oil. The reaction products were
isolated by flash chromatography[13] using ethyl acetate–hexane (1 : 10) as
eluent.
Reaction with microwave heating: In a porcelain crucible was added
p-methylphenol (0.12 g, 1.1 mmol) and the desired a,b-unsaturated car-
boxylic acid (1.1 mmol) followed by AlCl3 (0.60 g, 4.5 mmol). The mixture
was heated in a microwave oven (770 W) for 2 min, evolution of HCl during
the reaction was observed. After this time the temperature was allowed to
reach room temperature and 30 mL of distilled water were added to the
reaction mixture. Then, the mixture was extracted three times with ethyl
ether (15 mL) and, after drying over anhydrous sodium sulfate, the solvent
was removed under reduced pressure. The reaction products were isolated
by flash chromatography[13] using ethyl acetate–hexane (1 : 10) as eluent.
7-Hydroxy-3,4-dimethyl-2,3-dihydro-1H-inden-1-one (1):[10] Yellow oil,
conventional route (2–40%), microwaves (45%); EM (Mþ¼176–77%),
(161–100%), (133–31%), (77–38%); IR (neat, cmꢁ1
) 3379 (OH),
1674 (C¼C), 1204 (C-O); 13C NMR (50 MHz, CDCl3, Pendant) ꢀ 17.3
(C-8), 21.0 (C-9), 32.9 (C-3), 45.7 (C-2), 114.0 (C-6), 121.6 (C-7a),
127.1 (C-4), 139.3 (C-5), 155.7 (C-3a), 157.6 (C-7), 210.0 (C-1);

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PREPARATION OF 1-INDANONES
3197
3
1H NMR (200 MHz, CDCl3) ꢀ 1.33 (d, JH-H ¼ 7.1 Hz, H-8), 2.30
2
3
(s, H-9), 2.31 (dd, JH2A–H2B ¼ 19.1 Hz, JH2B-H3 ¼ 1.6 Hz, H-2b), 2.96
2
3
(dd, JH2A-H2B ¼ 19.1 Hz, JH2A-H3 ¼ 7.1 Hz, H-2a), 3.46 (m, H-3), 6.68
3
3
(d, JH-H ¼ 8.2 Hz, H-6), 7.25 (d, JH-H ¼ 8.2 Hz, H-5), 9.03 (s, OH).
1-(2-Hydroxy-5-methyl)phenyl-2-buten-1-one (2):[14] Yellow oil, con-
ventional route (4–40%) EM (Mþ ¼ 176–20%), (161–100%), (135–30%),
(105–10%), (77–30%); IR (neat, cmꢁ1) 1651 (C¼O), 1588 (C-C¼O);
13C NMR (75 MHz, CDCl3) ꢀ 19.0 (C-10), 20.8 (C-11), 118.4 (C-6), 119.4
(C-2), 125.8 (C-5), 129.8 (C-3), 137.4 (C-8), 138.1 (C-4), 145.8 (C-9), 161.6
1
3
(C-1), 194.1 (C-7); H NMR (300 MHz, CDCl3) ꢀ 2.04 (d, JH-H ¼ 6.6 Hz,
H-10), 2.32 (s, H-11), 6.90 (d, 3JH-H ¼ 8.6 Hz, H-6), 7.06 (d, 3JH-H ¼ 15.0 Hz,
3
3
3
H-8), 7.19 (dq, JH8-H9 ¼ 15.0 Hz, JH9-H10 ¼ 6.6 Hz, H-9), 7.29 (d, JH-H
¼
8.6 Hz, H-5), 7.58 (s, H-3), 12.54 (s, OH).
7-Hydroxy-4-methyl-3-pentyl-2,3-dihydro-1H-inden-1-one (3): Yellow
solid, m.p. ¼ 65–66ꢀC, conventional route (35–60%), microwaves (33%);
EM (Mþ ¼ 232–77%), (175–12%), (161–100%), (133–17%), (77–21%); IR
(KBr, cmꢁ1) 3366 (OH), 1680 (C¼C); 13C NMR (50 MHz, CDCl3, Pendant)
ꢀ 14.2 (C-12), 17.4 (C-13), 22.7 (C-11), 27.1 (C-9), 32.0 (C-10), 34.6 (C-8),
38.3 (C-3), 43.1 (C-2), 113.9 (C-6), 122.1 (C-7a), 126.0 (C-4), 139.3 (C-5),
1
155.7 (C-3a), 156.7 (C-7), 210.2 (C-1); H NMR (200 MHz, CDCl3) ꢀ 0.88
(m, H-12), 1.29 (m, H-8, H-9, H-10 and H-11), 2.29 (s, H-13), 2.43
2
2
3
(d, JH2A-H2B ¼ 19.1 Hz, H-2b), 2.83 (dd, JH2A-H2B ¼ 19.2 Hz, JH2A-H3
¼
3
7.4 Hz, H-2a), 3.38 (m, H-3), 6.69 (d, JH-H ¼ 8.2 Hz, H-6), 7.26
3
(d, JH-H ¼ 8.2 Hz, H-5), 9.03 (s, OH). C15H20O2 (232.32): Anal. Calcd.
C 77.50%, H 8.70%. Found C 77.69%, H 8.71%.
CONCLUSION
We have developed a facile and effective procedure for the synthesis
1-indanone from p-methylphenol and a,b-unsaturated carboxylic acids
using microwave radiation. Further studies involving the bioactivity of
these products and the optimization and amplification of this reaction are
in progress.
ACKNOWLEDGMENT
The authors thanks Marcus Henrique (Polo Xistoquımico IQ/UFRJ)
and Dr. Rosane San Gil and Cristiane Parpinelli (Lab. NMR of IQ/UFRJ)
for some of the spectral analyses.

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3198
SILVA, FIGUEROA-VILLAR, AND AGUIAR
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Received in the USA October 24, 2001