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Synlett 2011(11): 1585-1591  
DOI: 10.1055/s-0030-1260795
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Microwave-Accelerated Alkylation of Arenes/Heteroarenes with Benzylic Alcohols Using Antimony(III) Chloride as Catalyst: Synthesis of O-Heterocycles

Prashant Shuklaa, Manoj K. Choudharyb, Sandip K. Nayak*b
a NAA Unit of CFSL, Hyderabad at Analytical Chemistry Division, Bhabha Atomic Research Centre, Mumbai 400085, India
b Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai 400085, India
Fax: +91(22)25505151; e-Mail: sknayak@barc.gov.in;
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Publication History

Received 11 February 2011
Publication Date:
15 June 2011 (online)

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Abstract

An efficient protocol for alkylation of electron-rich arenes/heteroarenes with benzylic alcohols under microwave irradiation using antimony(III) chloride as catalyst has been developed. The mild reaction conditions, high yields, operational simplicity, and applicability to various substrates render the approach a useful route for the synthesis of diaryl/triarylalkane. In addition, a new route for the conversion of ortho-alkenylated phenols into functionalized O-heterocycles has been accomplished.

Key words

antimony(III) chloride - alkylation - arenes - microwave - oxygen heterocycles

23

Typical Procedure for the Alkylation of 1,3-Dimethoxy-benzene (1) with 1-Phenylethanol (2a) Followed by Demethylation
1,3-Dimethoxybenzene (1, 0.276 g, 2 mmol), 1-phenyl-ethanol (2a, 0.268 g, 2.2 mmol), and SbCl3 (0.068 g, 0.30 mmol) were mixed with dry MeCN (2 mL) in an Anton Paar microwave vessel and sealed with a cap. The resulting mixture was irradiated with microwave (400 W) for 25 min when 2a was fully consumed (checked by TLC). The reaction mixture was quenched with sat. aq NaHCO3 solution (1 mL), and the viscous mass thus obtained was dissolved in EtOAc and passed through Celite to remove metal salts. The Celite bed was thoroughly washed with EtOAc, and the filtrate was washed with H2O, brine, and dried (MgSO4). Removal of solvent yielded the crude product which was dried under vacuo and then dissolved in dry CH2Cl2 (5 mL). The solution was cooled (-20 ˚C), and BBr3 (0.5 mL, 5 mmol) was added. The solution was slowly brought to 0 ˚C. The dark brown reaction mixture was stirred at 0 ˚C for 2 h when TLC showed complete disappearance of the starting compound. The reaction mixture was quenched with ice-water, and the product was extracted with CH2Cl2. The organic layer was washed with brine and dried (Na2SO4). The solvent was removed under vacuo, and the residue was purified by chromatography (silica, eluant: CHCl3-MeOH) to get pure monoalkylated and dialkylated products 3a and 3b, respectively. 4-(1-Phenylethyl)benzene-1,3-diol (3a)
Yield 65%; thick oil. IR (neat): ν = 3400, 3025, 2968, 2932, 1605, 1517, 1451, 1215, 1113, 972, 909, 758, 735, 701 cm-¹. ¹H NMR (200 MHz, CDCl3): δ = 7.11-7.25 (m, 5 H), 6.98 (d, 1 H, J = 8.3 Hz), 6.32 (dd, 1 H, J = 8.3, 2.4 Hz), 6.17 (d, 1 H, J = 2.4 Hz), 4.61 (br s, 2 H), 4.20 (q, 1 H, J = 7.1 Hz), 1.50 (d, 3 H, J = 7.1 Hz). ¹³C NMR (50 MHz, CDCl3): δ = 154.7, 154.0, 145.8, 128.7, 128.6, 127.4, 126.3, 124.8, 107.8, 103.5, 38.0, 21.1. Anal. Calcd for C14H14O2: C, 78.48; H, 6.59. Found: 78.11; H, 6.38.
4,6-Bis(1-phenylethyl)benzene-1,3-diol (3b)
Yield 14%; thick oil. IR (neat): ν = 3522, 3025, 2968, 2932, 1605, 1517, 1506, 1451, 1215, 1113, 972, 909, 759, 735, 703 cm-¹. ¹H NMR (200 MHz, CDCl3): δ = 7.10-7.28 (m, 10 H), 7.05 (s, 1 H), 6.11 (s, 1 H), 4.20 (q, 2 H, J = 7.2 Hz), 1.54 (d, 6 H, J = 7.2 Hz). ¹³C NMR (50 MHz, CDCl3): δ = 152.4, 145.7, 128.6, 127.4, 127.2, 127.0, 126.3, 124.1, 104.3, 38.5, 21.2. Anal. Calcd for C22H22O2: C, 82.99; H, 6.96. Found: 82.64; H, 6.68.
4- tert -Butyl-2-(1,3-diphenylallyl)phenol (29)
Yield 67%; thick oil. IR (neat): ν = 3447, 2963, 2928, 1491, 1261, 752, 698 cm-¹. ¹H NMR (200 MHz, CDCl3): δ = 7.10-7.37 (m, 12 H), 6.64-6.75 (m, 2 H), 6.35 (d, 1 H, J = 16.0 Hz), 5.07 (d, 1 H, J = 7.1 Hz), 1.23 (s, 9 H). ¹³C NMR (50 MHz, CDCl3): δ = 151.2, 143.7, 142.2, 137.2, 131.8, 131.5, 128.7, 127.4, 126.7, 126.4, 124.7, 115.9, 114.8, 49.1, 34.2, 31.5. Anal. Calcd for C25H26O: C, 87.68; H, 7.65. Found: 87.31; H, 7.41.
5-Methoxy-2-(1-phenylbut-3-enyl)phenol (32)
Yield 68%; thick oil. IR (neat): ν = 3420, 3026, 1614, 1597, 1200, 1150, 698 cm-¹. ¹H NMR (200 MHz, CDCl3): δ = 7.19-7.37 (m, 5 H), 7.16 (d, 1 H, J = 8.5 Hz), 6.50 (dd, 1 H, J = 8.5, 2.5 Hz), 6.34 (d, 1 H, J = 2.5 Hz), 5.70-5.78 (m, 1 H), 4.95-5.09 (m, 2 H), 4.21 (t, 1 H, J = 7.8 Hz), 3.76 (s, 3 H), 2.74-2.84 (m, 2 H). ¹³C NMR (50 MHz, CDCl3): δ = 158.9, 154.2, 144.1, 136.9, 128.7, 128.4, 127.9, 126.2, 123.2, 116.1, 105.9, 102.3, 55.1, 43.7, 39.1. Anal. Calcd for C17H18O2: C, 80.28; H, 7.13. Found: 79.91; H, 6.87.
Typical Procedure for the Intramolecular Cyclization of 4- tert -Butyl-2-(1,3-diphenylallyl)phenol (29) with Copper(II) Bromide To a solution of 29 (0.342 g, 1 mmol) in dry MeCN (5 mL), was added CuBr2 (0.536 g, 2.4 mmol) and stirred at ambient temperature. After completion of the reaction (5 min, checked by TLC) MeCN was removed under vacuo, and the crude product was quenched with H2O, dissolved in EtOAc, and the suspension was passed through Celite. The organic layer was washed with brine and dried (Na2SO4). The solvent was removed under vacuo, and the residue was purified by chromatography (silica, eluant: hexane-EtOAc) to get pure 33.
6- tert -Butyl-3-bromo-2,4-diphenyl chroman (33)
Single diastereomer; yield 96%; colorless solid; mp 240-241 ˚C. IR (neat): ν = 2955, 1497, 1238, 1005, 696 cm-¹. ¹H NMR (200 MHz, CDCl3): δ = 7.26-7.49 (m, 11 H), 6.86 (d, 1 H, J = 8.6 Hz), 6.67 (d, 1 H, J = 1.8 Hz), 5.17 (d, 1 H, J = 9.8 Hz), 4.44-4.63 (m, 2 H), 1.14 (s, 9 H). ¹³C NMR (50 MHz, CDCl3): δ = 152.4, 144.4, 141.9, 138.7, 129.3, 128.9, 128.5, 128.4, 127.9, 127.4, 126.7, 125.2, 124.1, 116.2, 82.6, 57.4, 53.9, 34.1, 31.3. ESI-MS: m/z = 421 [M+]. Anal. Calcd for C25H25BrO: C, 71.26; H, 5.98. Found: 70.98; H, 5.73.
2-(Bromomethyl)-3,4-dihydro-7-methoxy-4-phenyl-2 H -chromene (34)
Mixture of syn and anti isomers; yield 86%; thick oil. IR (neat): ν = 2930, 1609, 1504, 1491, 1206, 1051, 752 cm-¹. ¹H NMR (200 MHz, CDCl3): δ = 7.13-7.34 (m, 7 H), 6.31 and 6.28 (2 s, 1 H), 4.36-4.48 (m, 1 H), 3.53-3.83 (m, 6 H), 2.85-2.98 (m, 1 H), 2.16-2.26 (m, 1 H). ¹³C NMR (50 MHz, CDCl3): δ = 155.3, 155.1, 154.0, 153.4, 142.8, 141.0, 132.6, 131.4, 128.9, 128.7, 128.1, 127.5, 127.2, 126.8, 124.1, 121.7, 102.5, 102.3, 101.7, 101.3, 56.3, 56.2, 50.9, 42.1, 41.8, 41.2, 41.1, 36.6, 36.5, 29.6. ESI-MS: m/z = 333 [M+]. Anal. Calcd for C17H17BrO2: C, 61.28; H, 5.14. Found: 60.91; H, 4.87.