Synthesis of bromoaminoindane and bromoaminoindanone derivatives

Article abstract of DOI:10.3184/174751913X13636300018867

The bromination reactions of 5-aminoindane, 5-acetamidoindane, and 5-acetamidoindan-1-one were investigated using NBS, molecular bromine and photobromination, and the optimum reaction conditions were presented. The reaction of 5-aminoindane with glacial acetic acid at reflux temperature resulted in the formation of 5-acetamidoindane in high yield. 5-Acetamidoindan-1-one was generated by the reaction of 5-acetamidoindane with CrO₃ in acetic acid. Selective bromination at C-6 position of 5-acetamidoindane was achieved by treatment of title compound with bromine in acetic acid and thus afforded 5-acetamido-6-bromoindane. Further bromination reactions of bromoindanones were achieved in various reaction conditions.

Full text of DOI:10.3184/174751913X13636300018867

232 RESEARCH PAPER
APRIL, 232–235
JOURNAL OF CHEMICAL RESEARCH 2013
Synthesis of bromoaminoindane and bromoaminoindanone derivatives
Makbule Yilmaza, Ahmet Tutarb* and Ramazan Erenlerc
aDuzce University, Faculty of Art and Science, Department of Chemistry, TR-81620 Duzce, Turkey
bSakarya University, Faculty of Art and Science, Department of Chemistry, TR-54187 Sakarya, Turkey
cGaziosmanpasa University, Faculty of Art and Science, Department of Chemistry, TR-60240Tokat, Turkey
The bromination reactions of 5-aminoindane, 5-acetamidoindane, and 5-acetamidoindan-1-one were investigated
using NBS, molecular bromine and photobromination, and the optimum reaction conditions were presented. The
reaction of 5-aminoindane with glacial acetic acid at reflux temperature resulted in the formation of 5-acetamidoin-
dane in high yield. 5-Acetamidoindan-1-one was generated by the reaction of 5-acetamidoindane with CrO3 in acetic
acid. Selective bromination at C-6 position of 5-acetamidoindane was achieved by treatment of title compound with
bromine in acetic acid and thus afforded 5-acetamido-6-bromoindane. Further bromination reactions of bromoinda-
nones were achieved in various reaction conditions.
Keywords: bromination reactions, bromoaminoindane, bromoaminoindanone
The brominations of arylhydrocarbons are important synthetic
processes.1–4 Brominated hydrocarbons are precursors in the
preparation of organometallic reagents5 as well as the metal
mediated coupling reactions.6–8 Indanes have found extensive
application in medicinal chemistry.9 In addition, they exhibit
the luminescent properties.10 Bromoindenones are important
precursors for synthesis of ninhydrin derivatives.11 In previous
articles, we have reported the facile synthesis of mono- and
dibromoindenones from indane. Bromoindenone was con-
verted to the benzo[c]fluorenone skeleton.12 We also examined
the products of bromination of 5-methoxyindane. When
3-bromo-5-methoxy-1H-inden-1-one was heated in a sealed
glass tube at 85–90 °C underwent a [2+4] cycloaddition
reaction to form 5-bromo-3,10-dimethoxy-7H-benzo[c]-
fluoren-7-one.13
Aminoindanes are useful building blocks for many biologi-
cally important compounds, such as HIV (human immunode-
ficiency virus) protease inhibitors14 and neuroprotective
agents.15 5-Aminoindane and its derivatives play a key role
as intermediates for developing medicinally valuable
compounds.16,17
Although there are many studies of indane derivatives, the
bromination of 5-aminoindane and 5-acetaminoindan-1-one
has not been reported. Since bromine can be a good leaving
group, bromination of these compounds leads to valuable
functionalised intermediates. We have synthesised bromoami-
noindane and bromoaminoindanone derivatives as precursors
for the synthesis of medicinally important compounds.
acidic. Long reaction times also promoted the hydrolysis since
this did not take place in the formation of compounds 1 and 8.
In the formation of compound 7, 1 equiv. of bromine was used
whereas in the formation of compound 4, 5 and 6, 3 equiv. of
bromine were used. Hence, plenty of HBr was formed to
catalyse the hydrolysis of the amide group. In this work
PEG-400 was used as a green solvent. The low cost, reduced
flammability and toxicity, recyclability, easy degradation,
and miscibility with a wide variety of organic solvents, led to
PEG-400 being used as an alternative solvent in organic syn-
thesis.18 In this reaction, NBS supplied the bromine that were
attached to the aromatic ring of compound 4 and the alpha
positions of compounds 5 and 6 by electrophilic substitution
reactions. In the formation of compound 4, NBS provided the
electrophile and the enol forms of the compound 4 and 5 acted
as electron-rich alkenes that reacted with bromine electro-
philes. In the 1H NMR spectrum of compound 4, H-7 appeared
at δ 7.52 as a doublet with a coupling constant of 8.3 Hz
coupled to H-6 (δ 6.73, J = 8.3 Hz). The signal that appeared
at δ 4.82 was a broad singlet that could be attributed to NH-2.
Two signal groups observed in the aliphatic region were
assigned to the aliphatic protons H-2 and H-3. In the 13C NMR
spectrum (with APT), nine resonances were observed (two
methylene, two methine, four quaternary, and one carbonyl
carbon) in agreement with the structure, 5-amino-4-bromo-
indan-1-one (4). The second compound formed in this reaction
was 5-amino-2,2,4-tribromo-indan-1-one (5) in which two
1
bromines were attached to the alpha carbon. In the H NMR
spectrum, the H-7 proton resonated at δ 7.36 as a doublet with
an ortho coupling constant (8.3 Hz). The H-6 signal at δ 6.63
was a doublet coupled to H-7. The aliphatic protons appeared
at δ 3.90 as a singlet. The third compound was 5-amino-2,4-
dibromo-indan-1-one (6). In the 1H NMR spectrum, ABX and
AB spin systems were observed in the aliphatic and aromatic
regions, respectively. The signals observed at δ 3.31 as a
doublet of doublets with vicinal and geminal coupling were
assigned to H-3′. H-3 resonated at δ 3.71 as a doublet of
doublets with coupling constants of 7.5 Hz and 18.6 Hz. H-3′
resonated 0.4 ppm upfield from the H-3 proton due to γ-gauche
effect of H-3′ with bromine, caused by a cis orientation of H-3′
and the bromine. The H-2 signal appeared at δ 4.67 as a
doublet of doublets coupled with H-3′ and H-3 as 3.0 Hz and
7.5 Hz, respectively. Due to the electron-withdrawing effect of
the neighbouring carbonyl group, H-2 resonated further down-
field than H-3 and H-3′. The aromatic protons, H-6 and H-7
were observed at δ 6.78 and δ 7.63, respectively. In this reac-
tion, when the reaction time was 6 days, the selective bromina-
tion at the C-4 position of 5-acetaminoindan-1-one (3) was
accomplished without hydrolysis of the acetyl group, and
Results and discussion
The treatment of 5-aminoindane (1) with glacial acetic acid
under reflux temperature for 2 h gave a quantitative yield of
5-acetamidoindane (2). The acetyl group made the compound
less reactive toward the electrophilic addition. Because of the
biological importance of indanone derivatives, the oxidation of
5-acetamidoindane (2) was accomplished with CrO3 in acetic
acid at 55 °C for 1h. This afforded after the addition of propan-
2-ol, the corresponding 5-acetamidoindan-1-one (3) in a yield
of 50%. The reaction of 5-acetamidoindan-1-one (3) with NBS
and NaClO4–SiO2 in PEG-400 at room temperaturefor 30 days
afforded the 5-amino-4-bromo-indan-1-one (4), 5-amino-
2,2,4-tribromo-indan-1-one (5) and 5-amino-2,4-dibromo-
indan-1-one (6) in a yield of 28%, 13%, 19%, respectively. The
acetamide was hydrolysed to the amine by the HBr which was
formed during the reaction causing the medium to become
* Correspondent. E-mail: atutar@sakarya.edu.tr

JOURNAL OF CHEMICAL RESEARCH 2013 233
N-(4-bromo-2-1-oxo-indan-5-yl)acetamide (7) was formed in
a yield of 20% and crystallised from dichloromethane and
hexane, forming needles. The 1H NMR spectrum of the mono-
bromide (7) exhibited an AA’BB’ splitting pattern for the ali-
phatic protons. Part of the system appeared at δ 3.05 that was
further downfield than the B part (δ 2.72). Selective bromina-
tion at the C-6 position of 5-acetoaminoindane (2) was achieved
by treatment of the title compound (2) with 1.2 equiv. of bro-
mine in acetic acid at 15 °C for 1h, affording the N-(5-bromo-
indan-6-yl)acetamide (8). The 1H NMR spectra of compound 8
consisting of two characteristic signals, indicated that the
bromine was bound to C6. The signals observed at δ 8.14 and
δ 7.38 belonged to H-4 and H-7, respectively. Other indication
of bromine located at C-6 is the para coupling constant
between the H-4 and H-7, which was very low. The protons
appeared as broad singlets. Further bromination of the title
compound (8) afforded the tetrabromide (9) (yield 25%),
which was an intermediate containing four bromines, all result-
ing from addition and elimination taking place simultaneously.
The 1H NMR spectrum confirmed the proposed structure. The
proton integral established that the molecule contains seven
protons. The aromatic protons appeared as singlets at δ 8.58
and δ 7.49 belonged to H-7 and H-4, respectively. The
signal for the H-1 was observed at δ 5.42 as a singlet. The
NH resonance de-shielded at δ 7.69 due to the carbonyl
electron-withdrawing effect. The treatment of 5-aminoindane
(1) with NBS, SiO2 and NaClO4 in dichloromethane at room
temperaturefor 24 h led to the bromination of the aromatic
ring, and 4,6-dibromo-indane-5-amine (10) was formed in a
yield of 75%. The reaction proceeded by an electrophilic aro-
matic substitution reaction mechanism. Sodium perchlorate
and SiO2 were used as the acidic catalyst. 5-Amino-4,6-dibro-
moindane (10) oxidised with CrO3 and 2-propanol in acetic
acid to corresponding products, 5-amino-2,2,4,6-tetrabromo-
indan-1-one (11) (5%), 5-amino-4,6-dibromo-indan-1-one
(12) (10%), 5-amino-2,4,6-tribromo-indan-1-one (13) (5%).
Interestingly, although there was no bromine source in the oxi-
dation reaction of compound 10, the brominated compounds,
1
tribromide (13) and tetrabromide (11) were formed. The H
NMR spectrum of tetrabromide 11 was quite simple. H-3’s
appeared at δ 4.12 as a singlet while H-7 was observed at δ
7.99 as a singlet. The 1H NMR spectrum of second compound
(12) formed in this reaction, exhibited AA’BB’ spin system of
the aliphatic protons. The part of the system appeared at δ 2.96
whereas the B part was observed at δ 2.71. The signal of the
aromatic proton was resonated at 7.82 as a singlet. The reac-
tion of dibromoindanone 12 with NBS and NaClO4–SiO2 in
PEG-400 at room temperature for 6 days yielded the corre-
sponding tetrabromide (11) and tribromide 13 in a yield of
13% and 18%, respectively (Scheme 1).
Scheme 1 Synthesis of bromoaminoindane and bromoaminoindanone derivatives.

234 JOURNAL OF CHEMICAL RESEARCH 2013
Scheme 2 Photobromination of 5-acetaminoindanone.
mixture was diluted with water (20 mL), extracted with diethyl ether
(3×50 mL), dried (Na2SO4). After removal of the solvent, the residue
was chromatographed on silica gel and eluted with dichloromethane/
hexane (5/1) to afford the three compounds.
The 5-acetamidoindan-1-one (3) reacted with NBS in carbon
tetrachloride while irradiation with a 250 W projector lamp
for 3.5 h gave the dibromide 14 (3%) and tribromide 15 (9%)
(Scheme 2).
5-Amino-4-bromo-indan-1-one (4): Crystallised from dichloro-
methane-hexane yielded the white needles20 (0.19 g, 28%). M.p.
163 °C. 1H NMR (400 MHz, CDCl3): δ 7.52 (d, J = 8.3 Hz, 1H, H-7),
6.72 (d, J = 8.3 Hz, 1H, H-6), 4.82 (brs, 2H, NH-2), 2.99 (m, 2H, H-2),
2.68 (m, 2H, H-3). 13C NMR (100 MHz, CDCl3): δ 204.4, 157.5,
150.0, 129.3, 124.2, 114.9, 105.5, 36.4, 27.3. IR: υ/cm−1 3458, 3327,
3192, 1680, 1618, 1576, 1489, 1425, 1334, 1265, 1112, 810. Anal.
Calcd for C9H8BrNO: C, 47.82, H, 3.57. Found: C, 47.75, H, 3.63%.
The HPLC-TOF (m/z), calcd, 224.9789; found; 224.9796 [M+H]+.
5-Amino-2,2,4-tribromo-indan-1-one (5): 0.15 g, 13%. M.p.
180 °C. 1H NMR (300 MHz, CDCl3); δ 7.36 (d, J = 8.4 Hz, 1H, H-6),
6.63 (d, J = 8.4 Hz, 1H, H-2), 4.85 (brs, 2H, NH-2), 3.90 (s, 2H, H-3).
13C NMR (75 MHz, CDCl3, d-DMSO): δ 191.3, 153.9, 150.2, 127.0,
118.1, 116.1, 102.4, 57.1, 53.6. IR: υ/cm−1 3470, 3350, 3300, 3217,
2361, 1701, 1616, 1577, 1448, 1416, 1346, 1284, 1261, 1128. Anal.
Calcd for C9H6Br3NO: C, 28.16; H, 1.58. Found: C, 28.09, H, 1.21%.
The HPLC-TOF (m/z), calcd, 380.800; found; 380.8012 [M+H]+.
5-Amino-2,4-dibromo-indan-1-one (6): 0.18 g, 19%. 1H NMR
(400 MHz, CDCl3): δ 7.63 (d, J = 8.4 Hz, 1H, H-7), 6.79 (d, J =
8.4 Hz, 1H, H-6), 4.92 (brs, 2H, NH-2), 4.66 (dd, J = 3.0 Hz, J =
7.5 Hz, 1H, H-2), 3.70 (dd, J = 7.5 Hz, J = 18.6 Hz, 1H, H-3), 3.31
(dd, J = 3.0 Hz, 18.6 Hz, 1H, H-3′). 13C NMR (75 MHz, CDCl3):
δ 196.9, 153.7, 151.1, 125.7, 125.5, 115.6, 104.6, 44.4, 39.2. IR:
υ/cm−1 3452, 3435, 3354, 3313, 3196, 2360, 1683, 1618, 1579, 1344,
1116. IR (KBr): 3452, 3435, 3354, 3313, 3196, 2360, 1683, 1618,
1579, 1423, 1344, 1290, 1261, 1116, 823.Anal. Calcd for C9H7Br2NO:
C, 35.45; H, 2.31. Found: C, 35.31, H, 2.39%. The HPLC-TOF (m/z),
calcd, 302.8894; found; 302.8922 [M+H]+.
The 250 W lamp was the optimum reaction condition. If
the irradiation was lower than 250 W, the products were not
formed. Because of the irradiation, some part of the starting
material was decomposed, therefore the yields were poor.
Experimental
All bromination reactions were performed in the dark except the
photobrominations which were carried out at in daylight. Commercial
reagents were purchased from standard chemical suppliers and puri-
fied if needed. Flash column chromatography was carried out on silica
gel 60 (230–400 mesh, E. Merck). Melting points were determined
with a Büchi B-540 apparatus and are uncorrected. 1H and 13C NMR
spectra were recorded on 300 MHz and 400 MHz Bruker instruments.
Chemical shifts are in ppm from Me4Si, generated from the CDCl3. IR
spectra were taken with Shimadzu spectrometer. Elemental analyses
were performed on Flash 2000 Combustion CHNS/O Analyser.
HPLC-TOF analysis was performed on Agilent 6210 TOF-LC/Ms
with Zorbax SB-C18 column (4.6 × 150 mm, 2.7 µm (Agilent Tech-
nologies) with injection volume of 10 µL. The mobile phase consisted
of the eluent A- water with 0.1% formic acid and 10 mM ammonium
formate and B- acetonitrile. The flow rate was 0.7 mL min−1 at 35 °C.
The gradient program was fixed as follow: 0–1 min, 10% B; 1–8 min,
95% B; 8–11 min. % 95 B; 11–11, 1 min. 10% B; 11, 1–13 min. 10%
B. Column temperature was 35 °C. Total time of evaluation was
20 min. TOF analysis were carried out in positive ion mode, gas tem-
perature, 325 °C, drying gas flow, 7 mL min−1, fragmentor voltage,
175 V.
N-(Indan-5-yl)acetamide (2): A solution of 5-aminoindane 1
(0.39 g, 3.0 mmol) in glacial acetic acid (10 mL) was refluxed for 2h.
The reaction mixture was cooled to rt, diluted with water (20 mL), and
extracted with dichloromethane (2×25 mL), dried (MgSO4), concen-
trated and crystallised (hexane/dichloromethane) to form white
needles of 5-acetaminoindane (2) (0.50 g, 98%). M.p. 99–100 °C
(lit.16 99–101 °C) 1H NMR (300 MHz, CDCl3): δ 7.43–7.38 (m, 2H),
7.10–7.16 (m, 1H), 7.12 (s, 1H), 2.88 (m, 4H), 2.18 (s, 3H), 2.09 (m,
2H).
N-(4-Bromo-1-oxo-indan-5-yl)acetamide (7): A mixture of 5-
acetamidoindan-1-one 3 (0.19 g, 1.0 mmol), NBS (0.18 g, 1.0 mmol),
SiO2 (1.0 g) in PEG-400 (2.0 g) was stirred magnetically for 6 days at
rt. The reaction mixture was diluted with water (20 mL), extracted
with diethyl ether (3×50 mL) and dried (Na2SO4). After removal of the
solvent, the residue was chromatographed on silica gel and eluted
with dichloromethane/hexane (5/1) to afford the title compound.
It was crystallised from dichloromethane-hexane to yield the white
needles of N-(4-bromo-1-oxo-1H-indan-5-yl)acetamide (7)19 (53 mg,
1
20%). H NMR (300MHz, CDCl3): δ 8.48 (d, J = 8.4 Hz, 1H, H-7),
N-(1-Oxo-1H-indane-5-yl)acetamide (3): CrO3 (1.2 g, 12.0 mmol)
in aqueous glacial acetic acid (7.0 mL, 1/1 v/v) was added dropwise
over 55 °C over 1h to a solution of 5-acetamidoindane (2) (0.53 g,
3.0 mmol) in glacial acetic acid (7.0 mL). Isopropanol (4 mL) was
added to the reaction mixture which was cooled with ice-water, stirred
for additionally 10 min, diluted with water (30 mL), and extracted
with ethyl acetate (3×30 mL). It was dried (Na2SO4), concentrated,
and chromatographed on silica gel using dichloromethane/EtOAc
(4/1) as eluants to give N-(1-oxo-indane-5-yl)acetamide (3)19 (0.29 g,
7.86 (brs, 1H, NH), 7.70 (d, J = 8.4 Hz, 1H, H-6), 3.05 (part of the
AA’BB’, m, 2H, H-2), 2.72 (part B of the AA’BB’, m, 2H, H-3), 2.29
(s, 3H, Me). 13C NMR (75 MHz, CDCl3), δ 205.0, 168.7, 155.7, 141.4,
134.3, 124.0, 120.5, 111.5, 36.4, 27.8, 25.4. IR: υ/cm−1 995, 1038,
1117, 1232, 1248, 1316, 1364, 1402, 1522, 1660, 1681, 1700, 3244,
3339. Anal. Calcd for C11H-10BrNO2: C, 49.28, H, 3.76. Found: C,
49.15, H, 3.85%. The HPLC-TOF (m/z), calcd, 266.9895; found;
266.9908 [M+H]+.
N-(5-Bromo-indan-6-yl)acetamide (8): A solution of bromine
(0.59 g, 3.7 mmol) in glacial acetic acid (2.0 mL) was added dropwise
at 10 °C to a solution of 5-acetamidoindane 2 (0.53 g, 3.0 mmol) in
glacial acetic acid (10 mL). The reaction mixture was stirred for 1h,
diluted with water (30 mL) and the solid part was separated by filtra-
tion. The solid material was washed with water (100 mL), and dried
in the oven at 80 °C to afford the product (8) (0.62 g, 81%). M.p.
1
50%). M.p. 174 °C. H NMR (300 MHz, CDCl3): δ 8.24 (brs, 1H,
NH), 7.99 (s, 1H, H-4), 7.66 (1H, d, J = 8.5 Hz, H-7), 7.27 (1H, d,
J = 8.5 Hz, H-6), 3.07–3.12 (m, 2H, H-2), 2.66–2.69 (m, 2H, H-3). 13
C
NMR (75 MHz, CDCl3): δ 206.4, 169.2, 157.7, 144.2, 133.0, 124.9,
118.9, 116.6, 36.7, 26.2, 25.1. IR: υ/cm−1 3427, 3143, 3118, 3084,
1683, 1674, 1604, 1556, 1489, 1421, 1373, 1340, 1301, 1265, 1101,
1037. Anal. Calcd for C11H-11NO2: C, 69.83; H, 5.86. Found: C,
69.95, H, 5.81%.
Bromination of N-(oxo-1H-indane-5-yl)acetamide (3): A mixture
of 5- acetamidoindan-1-one (3) (0.57 g, 3.0 mmol), NBS (1.60 g,
9.0 mmol), SiO2 (1.0 g), NaClO4 (0.2 g) in PEG-400 (2.0 g) was
stirred magnetically for 30 days at room temperature. The reaction
1
141–142°C (dichloromethane/hexane) (lit.21 140–142 °C). H NMR
(300 MHz, CDCl3): δ 8.11 (s, 1H), 7.52 (brs, NH, 1H), 7.36 (s, 1H),
2.87 (m, 4H), 2.22 (s, 3H, CH-3), 2.07 (m, 2H). IR: υ/cm−1 3271,
1659, 1576, 1522, 1399, 1367, 1283, 1022.
N-(1,2,3,6-Tetrabromo-1H-inden-5-yl)acetamide (9): A solution of
bromine (0.64 g, 4.0 mmol) in CCl4 (25 mL) dropwise during 2.5 h at

JOURNAL OF CHEMICAL RESEARCH 2013 235
reflux was added to a solution of N-(5-bromo-2,3-dihydro-1H-inden-
6-yl)acetamide 8 (0.25 g, 1.0 mmol) in CCl4 (25 mL) was added. After
the addition of brominewas completed, the reaction mixture was
stirred for 15 min. The solvent and excess bromine were then removed
in vacuo, the solid material was subjected to column chromatography
(silica gel), and eluted with hexane and dichloromethane (3/1) to give
the product. This was crystallised from hexane/dichloromethane to
yield yellow crystals of the tetrabromide (9)22 (0.12 g, 25%). M.p.
reaction mixture was stirring, the lamp was turned on. The reaction
was completed for 3.5 h, monitoring by TLC for consumption of the
starting material. The reaction mixture was cooled to the room tem-
perature, filtered, concentrated. The residue was chromatographed on
silica gel and eluted with dichloromethane and hexane (3/1) to yield
the dibromide (14) and tribromide (15).
N-(2,3-Dibromo-1-oxo-indan-5-yl)acetamide (14): 15 mg, 3%.
M.p. 210 °C. 1H NMR (300MHz, CDCl3): δ 7.43 (NH, s), 7.43 (1H, s,
H-2), 7.36 (1H, d, H-3), 7.34 (1H, d, H-1), 2.25 (3H, s). 13C NMR
(75 MHz, CDCl3): δ 184.9, 168.6, 144.2, 141.6, 139.2, 127.6, 126.1,
123.5, 120.4, 25.5. IR: υ/cm−1 847, 1101, 1220, 1232, 1338, 1517,
1707, 3360. Anal. Calcd for C11H7Br2NO2: C, 38.30, H, 2.05. Found:
C, 38.21, H, 2.16%.
N-(2,3,6-Tribromo-1-oxo-indan-5-yl)acetamide (15): 60 mg, 9%.
1H NMR (300MHz, CDCl3): δ 8.39 (1H, s),7.83 (brs, NH), 7.63 (1H,
s), 2.30 (s, 3H, CH-3). 13C NMR (75 MHz, CDCl3): δ 184.9, 168.8,
145.4, 143.4, 141.2, 127.4, 124.7, 123.8, 114.7, 112.3, 25.4. IR: υ/cm−1
758, 889, 1010, 1103, 1178, 1213, 1317, 1406, 1494, 1546, 1600,
1705, 1726, 2725, 2851, 2922, 3095, 3390. Anal. Calcd for
C11H6Br3NO2: C, 31.17, H, 1.43. Found: C, 31.29, H, 1.55%. The
HPLC-TOF (m/z), calcd, 420.7949; found; 420.7970 [M+H]+.
1
220 °C. H NMR (300 MHz, CDCl3): δ 8.58 (1H, s), 7.69 (brs, 1H,
NH-2), 7.49 (s, 1H), 5.42 (s, 1H), 2.27 (s, 3H, Me). 13C NMR
(75 MHz, CDCl3): δ 168.6, 142.5, 136.8, 135.6, 128.5, 124.6, 124.2,
118.8, 113.9, 49.4, 25.3. IR: υ/cm−1 993, 1080, 1244, 1274, 1400,
1462, 1514, 1579, 1660, 3242. Anal. Calcd for C11H7Br4NO: C, 27.03,
H, 1.44. Found: C, 27.12, H, 1.51%. The HPLC-TOF (m/z), calcd,
484.7261; found; 484.7295 [M+H]+.
4,6-Dibromo-indan-5-amine (10): NBS (0.75 g, 4.2 mmol), SiO2
(1.0 g) and NaClO4 (0.2 g, 1.63 mmol) was added to a solution of 5-
aminoindane 1 (0,27 g, 2.0 mmol) in CH-2Cl2 (25 mL). The mixture
was stirred for 2 days at room temperature, filtered and concentrated,
and column chromatographed on silica gel using a gradient of hexane
and ethyl acetate as eluents to give the dibromide (10)22 which was
1
recrystallised in dichloromethane (0.44 g, 75%). M.p. 220 °C. H
NMR (300 MHz, CDCl3): δ 7.22 (s, 1H, H-7), 4.41 (brs, 2H, NH-2),
2.95–2.84 (m, 4H), 2.02–2.12 (m, 2H). 13C NMR (75 MHz, CDCl3):
145.1, 140.0, 135.3, 127.0, 107.0, 106.6, 35.3, 33.5, 24.9. Anal. Calcd
for C9H9Br2N: C, 37.15, H, 3.12. Found: C, 37.21, H, 3.01%.
Oxidation of 4,6-dibromo-indan-5-amine (10): A solution of CrO3
(1.2 g, 12.0 mmol) in aqueous glacial acetic acid (7 mL,1:1 v/v) was
added dropwise to a solution of 5-amino-4,6-dibromoindane (10)
(0.58 g, 2.0 mmol) in glacial acetic acid (7.0 mL) at 55 °C. The reac-
tion mixture was stirred for 45 min, cooled with ice bath then isopro-
panol (4 mL) was added to the reaction mixuter. The mixture was
stirred additionally for 10 min, diluted with 20 mL of water, extracted
with ethyl acetate (3×15 mL). The combined extract was dried
(MgSO4), concentrated, and column chromatographed on silica gel
using a gradient mixture of hexane and dichloromethane (1/1) as elu-
ents to give the three products. All three compounds were crystallised
dichloromethane/hexane.
Electronic Supplementary Information
Spectral data have been deposited in the ESI available through
stl.publisher.ingentaconnect.com/content/stl/jcr/supp-data.
HPLC-QTOF/Ms and elemental analysis measurements were
performed at Cankiri Karatekin University so the authors are
grateful to Prof. Dr. Ibrahim Demirtas.
Received 13 January 2013; accepted 11 February 2013
Paper 1301723 doi: 10.3184/174751913X13636300018867
Published online: 19 April 2013
References
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5-Amino-2,2,4,6-tetrabromo-indan-1-one (11): 0.05g, 5%. M.p.
1
180 °C. H NMR (400 MHz, CDCl3): δ 8.02 (1H, s, H-7), 5.48 (brs,
2
R. Erenler, I. Demirtas, B. Buyukkidan and O. Cakmak, J. Chem. Res.,
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2H, NH-2), 4.15 (2H, s, H-3). 13C NMR (100 MHz, CDCl3): δ 189.7,
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HPLC-TOF (m/z), calcd, 458.7105; found; 458.7111 [M+H]+.
5-Amino-4,6-dibromo-indan-1-one (12): 0.06 g, 10%. M.p. 216 °C.
1H NMR (300 MHz, CDCl3): δ 7.82 (1H, s), 5.19 (brs, NH-2), 2.96 (A
part of AA’BB’), 2.71 (B part of AA’BB’). 13C NMR (75 MHz,
CDCl3): δ 203.6, 156.0, 147.1, 129.4, 127.5, 108.7, 105.5, 36.5, 27.5.
IR: υ/cm−1 997, 1144, 1335, 1425, 1560, 1676, 2926, 3390. Anal.
Calcd for C9H7Br2NO: C, 35.45, H, 2.31. Found: C, 35.32, H, 2.42%.
5-Amino-2,4,6-tribromo-indan-1-one (13): 0.04 g, 5%. M.p.
194.7 °C. 1H NMR (300 MHz, CDCl3): δ 7.91 (1H, s), 5.34 (brs, 2H,
NH-2), 4.61–4.65 (dd, J = 7.5 Hz, J = 3 Hz, 1H), 3.6–3.7 (dd, J = 18.6
Hz, J = 7.5 Hz, 1H), 3.21–3.29 (dd, J = 18.6 Hz, J = 3 Hz, 1H). 13C
NMR (75 MHz, CDCl3): δ 196.3, 152.3, 148.3, 128.9, 125.6, 109.4,
104.6, 44.1, 39.4. IR: υ/cm−1 930, 981, 1143, 1211, 1344, 1418, 1470,
1566, 1597, 1695, 3327, 3445. Anal. Calcd for C9H6Br3NO: C, 28.16,
H, 1.58. Found: C, 28.35, H, 1.64%.
3
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of 5-amino-4,6-dibromoindanone (12) (0.3 g, 1.0 mmol), NBS (0.53 g,
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for 6 days at rt. The reaction mixture was diluted with water (20 mL),
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of the solvent, the residue was chromatographed on silica gel, and
eluted with dichloromethane/hexane (5/1) to afford the corresponding
tetrabromoindanone (11) and tribromoindanone (13) in a yield of 13%
and 18% respectively.
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stirred solution of 5-acetaminoindanone 3 (0.3 g, 1.59 mmol) in CCl4
(70 mL) in photochemical reaction apparatus. Two condensers were
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