Methanesulfonic Acid → 2-[3-(2,3-Dihydroxypropoxy)phenyl]-3-methylbenzofuran

HRID 1980

Reaction equation

HRID 1980 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:8]2[O:9][C:10]3[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=3[C:12]=2[CH3:13])[CH:5]=[CH:6][CH:7]=1.C[O-].[Na+].[CH2:21]1[O:23][CH:22]1[CH2:24][OH:25].CS(O)(=O)=O>CO>[OH:23][CH:22]([CH2:24][OH:25])[CH2:21][O:1][C:2]1[CH:3]=[C:4]([C:8]2[O:9][C:10]3[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=3[C:12]=2[CH3:13])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 11164GlycidolHCID 10942334Sodium MethoxideHCID 189403532-(3-Hydroxyphenyl)-3-methylbenzofuran

Product 1

HCID 189403542-[3-(2,3-Dihydroxypropoxy)phenyl]-3-methylbenzofuran

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
200 °C

Procedure

The ester which results from the condensation of 2'-hydroxyacetophenone and m-anisic acid is converted to 2-(3-methoxyphenyl)-3-methylbenzofuran by reductive cyclization in dioxane with a titanium tetrachloride/zinc metal catalyst according to the method of Banerji and Nayak, J. Chem. Soc., Chem. Comm., (1990), 150. The 2-(3-methoxyphenyl)-3-methylbenzofuran (47.6 gm, 0.198 mol) is treated with several volumes of pyridine hydrochloride at 200° C. for about 6 hours to cleave the methyl ether moiety to the free hydroxyl group. Three volumes of water are added to the cooled reaction mixture and the system is extracted twice with ether. The ether extracts are combined, washed once with water and then dried over sodium sulfate. Removal of solvent by rotary evaporation affords the desired product, 2-(3-hydroxyphenyl)-3-methylbenzofuran. 2-(3-hydroxyphenyl)-3-methylbenzofuran (22.4 gm 0.1 mol) is dissolved in 100 mL of methanol in a 250 ml round bottom flask under an atmosphere of argon. To this well stirred solution is added sodium methoxide (0.54 gm, 0.01 mol). Glycidol (Aldrich, 8.14 gm, 0.11 mol) is added and the system is gradually heated and held at reflux for 18 hours. The solution is neutralized with methanesulfonic acid. The solvent is removed by rotary evaporation. The resulting product is heated on a Kugelrohr apparatus at 200° C. under a vacuum of 1 mm Hg, to remove any 3-methoxy-1,2-propanediol by-product, affording 2-[3-(2,3-dihydroxypropoxy)phenyl]-3-methylbenzofuran having the structure: ##STR55##

Workup

  1. temperaturethe system is gradually heated
  2. temperatureat reflux for 18 hours
  3. customThe solvent is removed by rotary evaporation
  4. customto remove any 3-methoxy-1,2-propanediol by-product

Sources & evidence

ORD record
ord-5dd2c77bb7de45af8bd5e3455820ca7e
Source dataset
uspto-grants-1998_03
Patent number
US05728671

Linked notes

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