m-Chloroperbenzoic acid → 2-[(4-Isopropoxy-3-methoxy-phenyl)ethynyl]-5-isopropoxy-4-methoxyphenol

HRID 1060256Notes

Reaction equation

HRID 1060256 reaction equation
ClC1C=C(C=CC=1)C(OO)=[O:6].[CH:12]([O:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]#[C:23][C:24]2[CH:31]=[C:30]([O:32][CH3:33])[C:29]([O:34][CH:35]([CH3:37])[CH3:36])=[CH:28][C:25]=2C=O)=[CH:18][C:17]=1[O:38][CH3:39])([CH3:14])[CH3:13]>C(Cl)Cl>[CH:12]([O:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]#[C:23][C:24]2[CH:31]=[C:30]([O:32][CH3:33])[C:29]([O:34][CH:35]([CH3:37])[CH3:36])=[CH:28][C:25]=2[OH:6])=[CH:18][C:17]=1[O:38][CH3:39])([CH3:13])[CH3:14]

Participants

4

Reactant 2

HCID 70297m-Chloroperbenzoic acidHCID 117838922-[(4-Isopropoxy-3-methoxy-phenyl)ethynyl]-5-isopropoxy-4-methoxybenzaldehyde

Product 1

HCID 219231432-[(4-Isopropoxy-3-methoxy-phenyl)ethynyl]-5-isopropoxy-4-methoxyphenolYield 92.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

m-Chloroperoxybenzoic acid [1.2 g, ALDRICH, 50% (remainder 3-chlorobenzoic acid and water), ca. 7.0 mmol] was added in portions over 0.25 h to a magnetically stirred mixture of 2-[(4-isopropoxy-3-methoxy-phenyl)ethynyl]5-isopropoxy-4-methoxybenzaldehyde (2.20 g, 5.75 mmol) and KHCO3 (1.73 g, 17.3 mmol) in CH2Cl2 (50 mL) maintained at 0° C. (ice-bath). The resulting slurry was stirred for a further 1 h between 0° C. and 18° C. then filtered through Celite® and the solids thus retained rinsed with CH2Cl2 (1×50 mL). The combined filtrates were concentrated under reduced pressure and the residue treated with NH3 (30 ml of a saturated methanolic solution). After 1 h at 18° C. the reaction mixture was concentrated under reduced pressure and the residue redissolved in CH2Cl2 (200 mL) then concentrated on to silica gel (8 g, 400-200 mesh). The resulting powder was loaded on top of a column of silica (40-10 mesh TLC grade, 10 cm wide×5 cm long) and eluted with 2:1, 1:1 and 1:2 hexane/CH2Cl2 then neat CH2Cl2 (250 ml of each). The appropriate fractions (Rf 0.3 in 1:2 hexane/CH2Cl2) were concentrated under reduced pressure to give the title compound (1.97 g, 92%) as white crystalline masses, mp 130-1° C. IR(KBr disc, cm−1) 3404, 2981,2935, 1620, 1573, 1513, 1467, 1450, 1418, 1383, 1373, 1330, 1269, 1240, 1214, 1166, 1135, 1113, 951. 1H NMR(300 MHz, CDCl3) δ7.03 (dd, J=1.8, 8.4 Hz, 1H), 7.00 (d, J=2.1 Hz, 1H), 6.87 (s, 1H), 6.81 (d, J=8.4 Hz, 1H), 6.53 (s, 1H), 5.81 (s, 1H), 4.52 (septet J=6.0 Hz, 2H), 3.82 (s, 3H), 3.78 (s, 3H), 1.35 (d, J=6.0 Hz, 12H). 13C NMR+APT (75.5 MHz, CDCl3) δ151.8 (C), 149.7 (C), 149.3 (C), 147.8 (C), 143.6 (C), 124.6 (CH), 115.0 (C), 114.7 (CH), 114.6 (CH), 114.3 (CH), 102.0 (CH), 100.1 (C), 94.7 (C), 82.2 (C), 71.1 (CH), 71.0 (CH), 56.4 (CH3), 55.7 (CH3), 21.9 (CH3), 21.8 (CH3). MS (70eV) m/z (%): 370 (M+•), 355(2, M+•−CH3), 328(18, M+•−CH(CH3)2], 327 (20, M+•CH2CHCH3), 286 (100, M+•−2×CH2CHCH3), 271 (42, M+•−2×CH2CHCH3—CH3). Anal. Calcd for C22H26O5 C, 71.33; H, 7.07. Found: C, 70.91; H. 7.24.

Workup

  1. filtrationthen filtered through Celite®
  2. washthe solids thus retained rinsed with CH2Cl2 (1×50 mL)
  3. concentrationThe combined filtrates were concentrated under reduced pressure
  4. additionthe residue treated with NH3 (30 ml of a saturated methanolic solution)
  5. concentrationAfter 1 h at 18° C. the reaction mixture was concentrated under reduced pressure
  6. dissolutionthe residue redissolved in CH2Cl2 (200 mL)
  7. concentrationthen concentrated on to silica gel (8 g, 400-200 mesh)
  8. washeluted with 2:1, 1:1 and 1:2 hexane/CH2Cl2
  9. concentrationThe appropriate fractions (Rf 0.3 in 1:2 hexane/CH2Cl2) were concentrated under reduced pressure

Sources & evidence

ORD record
ord-27110459d2cf49ec89aa5a8bd907f242
Source dataset
uspto-grants-2003_02
Patent number
US06521757B1

Reaction notes

Loading…