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Table 3
References and notes
Preparation of chromanones 3a–3j via Friedel–Crafts reaction
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O
O
CN
1. TfOH/TFA
R
R
2. H2O
O
2a-j
one-pot
3a-j
11-98%
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Entry
1
Substrate
Chromanone
Isolated yield
95
CN
CN
O
PhO
PhO
O
O
2a
2b
PhO
O
O
3a
PhO
2
90
O
3b
Br
CN
O
7. Sato, K.; Lin, Y.; Amakasu, T. Bull. Chem. Soc. Jpn. 1969, 42, 2600–2604.
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2337–2340.
Br
3
4
58
85
O
2c
O
3c
O
CN
O
3d
O
2d
13. Booth, B. L.; Noori, G. F. M. J. Chem. Soc., Perkin Trans.
I 1980,
Br
X1
O
2894–2900.
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CN
ˇ
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5
73
O
X2
O
3e: X1 = H, X2 = Br (47%)
4e: X1 = Br, X2 = H (53%)
2e
CN
O
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1035–1050.
21. General procedure for the preparation of 3-aryloxypropanenitriles 2a–2j: To a
250 mL 3-necked round-bottomed flask, equipped with an overhead stirrer,
thermocouple, water-cooled condenser, and nitrogen inlet, was charged aryl
phenol (8.90 mmol) and acrylonitrile (58.6 mL, 890 mmol), 5 mol % potassium
carbonate (0.62 g, 4.45 mmol), and 10 mol % of tert-butanol (0.66 g,
8.90 mmol). The resulting slurry was refluxed for 8 h. The remaining 5 mol %
of potassium carbonate(0.62 g, 4.45 mmol) was added to the reaction mixture.
After being stirred in reflux for 36 h, the reaction mixture was cooled to rt, and
8 mol % of 85% phosphorous acid (0.82 g,7.12 mmol) was added, and stirred for
0.5 h. The excess acrylonitrile was distilled off under atmospheric pressure. The
resulting oily crude product was diluted with toluene (75 mL).The solution was
washed with 1 N NaOH (aq)/DMSO (4:1,80 mL Â 1). After phase separation, the
aqueous layer was extracted with toluene (25 mL). The combined organic
layers were washed with 1 N NaOH (aq)/DMSO (4:1, 20 mL Â 2),and 10 wt %
phosphorous acid (10 mL Â 1). The organic layer was concentrated and dried
under vacuum to give desired 3-aryloxypropanenitriles 2a–2j in 50–93% yield
(typical P95%purity).
6
7
85
11
O
2f
NO2
O
3f
O
CN
O
O2N
O
2g
3g
Me CN
O
O
8
98
98
60
2h
O
3h
Me
Me
Cl
Me
O
CN
9
O
2i
O
3i
Cl
CN
O
O
O
10
2j
3j
22. General procedure for the preparation of 4-chromanones 3a–3j: To a 25 mL 2-
necked round-bottomed flask, equipped with thermocouple and nitrogen inlet,
was charged 3-aryloxypropanenitriles 2a–2j (12.6 mmol) in 5 equiv of
TFA(4.86 mL, 63.0 mmol) solution. To the resulting solution was slowly
added 1.5 equiv of TfOH (1.67 mL, 17.7 mmol) at 0–5 °C. The resulting
solution was stirred at 0 °C for 5 h, and then at ambient temperature for 16–
24 h until the conversion of the reaction was >99%. The reaction mixture was
cooled to 0 °C. Then, 2 equiv of water (0.41 mL, 25.2 mmol) was added
dropwise at 0–10 °C. The resulting solution was stirred at room temperature
for 1–5 h. The reaction mixture was transferred to a separation funnel and
diluted with toluene (20 mL) and water (10 mL). After phase separation, the
aqueous layer was extracted with toluene (6 mL Â 1). The combined organic
layers were washed with water (9 mL Â 1) and concentrated. The pure 4-
chromanones 3a, 3b, 3d, 3f, 3h, and 3i obtained by crystallization of their
corresponding crude products in isopropanol (IPA) and the pure chromanones
3c, 3–4e, 3g and 3j were obtained by Biotage chromatographic purification
(EtOAc/hexanes from 10% to 80%).
acrylonitrile. We believe that the facile methodology will find
applications in the fields of organic and medicinal chemistry.
Acknowledgment
The authors thank Dr. Chengyi Chen for proof reading of the
manuscript.
Supplementary data
Supplementary data associated with this article can be found, in