3
18 JOURNAL OF CHEMICAL RESEARCH 2011
that when the substituent on the benzene ring was an electron-
donating group such as 3–OCH , 3,4-OCH , polyphosphoric
5-Methyl-3-oxo-indan-1-carboxylic acid (2c):Yellow powder, yield
1
−
5
1
2
4
4%, m.p. 134–136 °C; IR (KBr ): 3441, 2966, 1729(C=O),1491,
3
3
1
404, 1202, 885, 864, 833. H NMR (300 MHz, CDCl ), δ (ppm):
3
acid (PPA) was the preferred cyclising agent compared to
SOCl /AlCl , and a high yield (>70%) was obtainable.
.42 (3H, s, CH ), 2.85–2.94 (1H, m, H ), 3.10–3.17 (1H, m, H ),
3
2
2
2
3
.28–4.30 (1H, t, J = 2.4 Hz, H ), 7.46–7.48 (1H, d, J = 7.8 Hz,
1
Substituted 3-oxo-indan-1-carboxylic acid (2) have been
converted to the corresponding indan-1-carboxylic acid (3)
by Clemmensen reaction employing zinc amalgam, a hazard-
ArH ), 7.57 (1H, s, ArH ), 7.62–7.65 (1H, d, J = 7.8 Hz, ArH ), 11.26
6
4
7
(
1H, bs, COOH).
5,6-Dichloro-3-oxo-indan-1-carboxylic acid (2d): Off-white
2
,6,7
8
−1
ous reagent, as the reducing reagent . Olah had reported
trifluoromethanesulfonic acid/triethylsilane as a hydrogena-
tion reagent for the reduction of diaryl and alkyl, aryl ketones
powder, yield 48%, m.p. 202–204 °C; IR (KBr ): 3232, 1743 (C=O),
1
1
718, 1591, 1377, 1168, 884, 846, 824. H NMR (300 MHz, CDCl ),
3
δ (ppm): 2.94–3.08 (2H, m, H ), 4.30–4.39 (1H, t, J = 7.0 Hz, H ),
2
1
7
.80–7.87 (1H, s, ArH ), 7.92–7.99 (1H, s, ArH ). MS(ESI(-)70V, m/
7
4
to hydrocarbons. Based on this report, we used Et SiH–
3
−
z): 242.8 [M-H] .
CF COOH instead of zinc amalgam as the reducing agent in
3
the reduction of 3-oxo-indan-1-carboxylic acid derivatives,
and a satisfactory yield was readily achieved.
In addition, the HMBC ( H-detected heteronuclear multiple-
bond correlation) of 2b have indicated that H-4 (δ: 7.66–7.69)
was coupled with C-3 (carbonyl carbon δ: 202.7), which means
the cylisation of 3-chlorophenylsuccinic acid 1b was occurred
at the C-4 position in benzene, not the C-2 position to afford
Synthetic procedure for 2e–2f, exemplified by 6-methoxy-3-oxo-indan-
1-carboxylic acid (2e)
1
A suspension of 3-methoxyphenylsuccinic acid (1e) (2 g, 0.0089 mol)
in 30 g PPA was heated at 85°C (bath temperature) for 2 h. Then
crushed ice was added into the mixture. The aqueous layer was
extracted with EtOAc (3 × 50 mL), The combined extracts were then
treated with saturated aqueous Na CO , the separated aqueous layer
2
3
was acidified by conc. HCl to pH = 1–2 and extracted with EtOAc
(3 × 60 mL), which were washed successively with water, and brine,
6
-chloro-3-oxo-indan-1-carboxylic acid.
In conclusion, we have described a convenient method for
dried over anhydrous Na
pressure. The residual was recrystallised from ethanol-water to afford
e5as an off-white powder (1.36 g, yield 75%), m.p. 185–187 °C,
lit. 186–186.5°C.
2 4
SO , filtered and concentrated under reduced
the synthesis of the indan derivatives 3a–f, which has the
advantages of simplicity, mild reaction conditions, and avoids
the use of toxic reagents such as nitrobenzene and amalgamated
zinc. This route would be more acceptable in industry.
2
5
,6-dimethoxy-3-oxo-indan-1-carboxylic acid (2f). Off-white powder,
6
yield 70%, m.p. 188–191 °C, lit. 190–191 °C.
It should be noted that the target compounds 3c–f have not
been reported before. In addition, we found that the melting
points of 2a and 3a were not in accord with that reported by
Synthetic procedure for 3a–f, exemplified by 6-fluoroindan-1-carbox-
ylic acid (3a)
2
1
Et SiH (6.4 mL, 0.4 mol) was added to a solution of 2a (0.97 g,
literature, so their IR, MS, H NMR and HRMS data were
recorded in detail.
3
0
.05 mol) in anhyd. CF COOH (15 mL) at 40°C and stirred for 4 h.
3
The solution was concentrated and the pH was adjusted to 11–13 by
M NaOH. After another 15 min stirring at ambient temperature, the
2
Experimental
mixture was then acidified to pH 2–3 by addition of conc. HCl. The
precipitated solid was collected by filtration and washed with water
to give crude product which was recrystallised from petroleum ether–
EtOAc to yield 3a, as a colourless needles (0.69 g, yield 76%), m.p.
Chemicals and solvents were either purchased or purified by standard
techniques and used without any further purification. Substituted
phenylsuccinic acids (1a–f) were prepared from corresponding phe-
2
−1
9
82–84°C. (lit. 128–130°C); IR (KBr ): 2986, 2947, 1705 (C=O),
1
nylamine according to the literature method . Melting points were
1
596, 1487, 1446, 1417, 1217 (C-F), 921, 860, 818. H NMR
recorded on a RY-1 melting point apparatus and were uncorrected.
The IR spectra (in KBr pellets) were recorded on a Nicolet Impact
10 spectrometer. MS spectra were acquired on a Agilent 1100 series
LC/MSD Tarp(SL). The NMR spectra were recorded on a BRUKER
AV-300 NMR spectrometer using TMS as the internal standard. The
HRMS spectra were acquired on a Waters Micros Q-TOF apparatus.
(
3
300 MHz, CDCl ), δ (ppm): 2.35–2.56 (2H, m, H ), 2.85–2.95, 3.02–
.12 (2H, m, H ), 4.06–4.11 (1H, t, J = 7.2 Hz, H ), 6.91–6.97 (1H, m,
2 1
3
3
4
ArH ), 7.14–7.27 (2H, m, ArH ). 11.74 (1H, bs, COOH). MS(ESI
7
4,5
−
(
1
-)70V, m/z): 178.9 [M-H] . HRMS Calcd for C H O F (M-H)
10 8 2
79.0508. Found 179.0513.
-Chloroindan-1-carboxylic acid (3b): Colourless needles (from
6
7
petroleum ether–EtOAc), yield 72%, m.p. 126–128°C; (lit. 128–
Synthetic procedure for 2a–f, exemplified by 6-fluoro-3-oxo-indan-1-
carboxylic acid (2a)
a (5g, 0.023 mol) and thionyl chloride (20 mL) were refluxed together
−1
1
30°C). IR (KBr ): 3419, 2961, 2917, 1716 (C=O), 1507, 1437, 1247
1
(
C-F), 930, 817. H NMR (300 MHz, CDCl ), δ (ppm): 2.32–2.52
3
1
(
2H, m, H ), 2.83–3.09, 3.11–3.18(2H, m, H ), 4.04–4.09 (1H, t,
3
2
for 30 min, then the excess of thionyl chloride was removed under
vacuum. After the mixture was cooled, a suspension of the anhydrous
aluminium chloride (15.81 g, 0.11 mol) in 50 mL CH Cl was added
J = 7.5 Hz, H ), 7.14–7.21 (2H, m, ArH ,H ), 7.42 (1H, s, ArH ).
1
4
5
7
−
MS(ESI(-)70V, m/z): 194.9 [M-H] .
-Methylindan-1-carboxylic acid (3c): Colourless needles (from
petroleum ether–EtOAc), yield 54%, m.p. 74–76 °C; IR (KBr ):
2
2
5
into the solution. Stirring was continued for 3 h at ambient tempera-
ture. When the reaction was complete, the mixture was poured onto
ice-water, and extracted with EtOAc (3 × 60 mL). Then the combined
extracts were treated with saturated aqueous Na CO (3 × 60 mL), the
−
1
1
3
415, 2947, 1703 (C=O), 1596, 1486, 1414, 1228, 920, 830, 807. H
NMR (300 MHz, CDCl ), δ (ppm): 2.32 (3H, s, CH ), 2.29–2.43 (2H,
3
3
2
3
m, H ), 2.82–2.89, 2.92–3.11 (2H, m, H ), 3.99–4.04 (1H, t, J = 7.5 Hz,
3
2
combined aqueous layers were acidified by conc. HCl to pH = 1–2
and extracted with EtOAc (3 × 60 mL), which were washed succes-
sively with water and brine, dried over anhydrous Na SO , filtered
H ), 6.99–7.01 (1H, d, J = 7.5 Hz, ArH ), 7.06 (1H, s, ArH ), 7.27–
1
7
4
−
7
.30 (1H, d, J = 7.5 Hz, ArH ). MS(ESI(-)70V, m/z): 174.9 [M-H] .
6
2
4
HRMS Calcd for C H O (M-H) 175.0759. Found 175.0763.
10 11 2
and evaporated to dryness. The residue was recrystallised from petro-
5
,6-Dichloroindan-1-carboxylic acid (3d): White powder (from
leum–EtOAc to afford pure 2a as a white powder. (2.82g, yield 50%),
−1
petroleum ether–EtOAc), yield 64%, m.p. 145–147°C; IR (KBr ):
420, 2929, 1743 (C=O), 1718, 1591, 1168, 884, 846, 824. H NMR
2
−1
m.p. 96–98 °C. lit. m.p. 162–164 °C; IR (KBr cm ): 3475 (OH),
1
3
2
9
929, 2703, 1723,1694 (C=O), 1610, 1590, 1483, 1435, 1213 (C-F),
(
300 MHz, DMSO-d ), δ (ppm): 2.22–2.34 (2H, m, H ), 2.79–3.00
6
3
1
45, 885, 843. H NMR(300MHz, CDCl ), δ (ppm): 2.82–2.93 (1H,
3
(2H, m, H ), 4.00–4.05 (1H, t, J = 7.3 Hz, H ), 7.53 (2H, s, ArH ,
2
1
7
dd, J = 3.5 Hz, 19.1 Hz, H ), 3.07–3.15 (1H, dd, J = 8.1 Hz, 19.2 Hz,
−
2
ArH ). MS(ESI(-)70V, m/z): 228.9 [M-H] . HRMS Calcd for
4
H ), 4.23–4.26 (1H, m, H ), 7.02–7.12 (1H, m, ArH ), 7.36–7.39 (1H,
C H O Cl (M-H) 228.9823. Found 228.9829.
2
1
5
10
7
2
2
m, ArH ), 7.69–7.74 (1H, m, ArH ), 9.82 (1H, bs, COOH). MS (ESI
6-Methoxyindan-1-carboxylic acid (3e): Colourless crystalline
4
7
−
(
1
-)70V, m/z): 192.8 ([M-H] ). HRMS Calcd for C H O F (M-H)
solid (from petroleum ether–EtOAc), yield 70%, m.p. 104–106°C; IR
10
6
3
−
1
93.0301. Found 193.0305.
-Chloro-3-oxo-indan-1-carboxylic acid (2b): White powder,
(KBr ): 3414, 2947, 1706 (C=O), 1608, 1497, 1446, 1416, 1229, 915,
1
6
820. H NMR (300 MHz, CDCl ), δ (ppm): 2.30–2.50 (2H, m, H ),
3
3
7
1
yield 59%, m.p. 146–148 °C. (lit. 148–151 °C); H NMR(300 MHz,
2.79–2.89, 2.98–3.08 (2H, m, H ), 3.78 (3H, s, OCH ), 4.01–4.05 (1H,
2
3
DMSO-d6), δ (ppm): 2.88–2.90 (2H, m, H ), 4.31–4.34 (1H, m, H ),
t, J = 6.7 Hz, H ), 6.76–6.79 (1H, dd, J = 2.3 Hz, 8.1 Hz, ArH ),
1 5
2
1
7
.54–7.57 (1H, d, J = 8.1 Hz, ArH ), 7.64–7.67 (1H, d, J = 8.1 Hz,
6.96–6.97 (1H, d, J = 1.8 Hz, ArH ) 7.11–7.14 (1H, d, J = 8.2 Hz,
5
7
−
ArH ), 7.76(1H, s, ArH ), 13.06(1H, bs, COOH). MS (ESI(-)70V,
m/z): 208.7 ([M-H] ).
ArH ). 10.95 (1H, bs, COOH). MS(ESI(-)70V, m/z): 190.9 [M-H] .
4
7
4
−
HRMS Calcd for C H O (M-H) 191.0708. Found 191.0712.
11
11
3