Sulfuric Acid → 6-Bromo-2-cyclohexyl-3,4-dihydro-2H-benzopyran

HRID 256412Notes

Reaction equation

HRID 256412 reaction equation
[CH:1]1(Br)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Mg:8].[Br:9]C1C=C2C(=CC=1)OC(O)CC2.[CH:21]1([CH:27]([OH:38])[CH2:28][CH2:29][C:30]2[CH:35]=[C:34]([Br:36])[CH:33]=[CH:32][C:31]=2O)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.S(=O)(=O)(O)O>C(OCC)C.O1CCCC1.C(O)(=O)C.CCCCCC>[CH:1]1([Mg:8][Br:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Br:36][C:34]1[CH:33]=[CH:32][C:31]2[O:38][CH:27]([CH:21]3[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]3)[CH2:28][CH2:29][C:30]=2[CH:35]=1

Participants

11

Reactant 5

HCID 1118Sulfuric AcidHCID 7960Cyclohexyl bromideHCID 5462224MagnesiumHCID 109662696-Bromo-2-chromanolHCID 201636331-Cyclohexyl-3-(2-hydroxy-5-bromophenyl)propanol

Product 2

HCID 201636356-Bromo-2-cyclohexyl-3,4-dihydro-2H-benzopyranHCID 178419651HCID 178419651, compound

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of cyclohexylmagnesium bromide in ethyl ether (55 ml) was prepared from 15.6 g (96 mmole) cyclohexyl bromide and 2.56 g magnesium. This was added dropwise to a solution of 5.5 g (24 mmole) 6-bromo-2chromanol in 55 ml dry tetrahydrofuran, under nitrogen at -70° C. The reaction mixture was stirred at -78° C. for two hours, then at 0° C. for one hour and quenched by addition of 4.1 ml acetic acid. The solvents were evaporated in vacuo, the residual white gel diluted with 250 ml ethyl acetate, washed with 1N hydrochloric acid (100 ml), saturated sodium bicarbonate solution, and dried (Na2SO4). Evaporation of solvent afforded an oil which solidified upon trituration with hexane, 5.3 g, m.p. 124°-126° C. This was identified as the diol, 1-cyclohexyl-3-(2-hydroxy-5-bromophenyl)propanol. The diol was dissolved in 125 ml acetic acid, 2.5 ml concentrated sulfuric acid added and the mixture heated at reflux for 16 hours. After evaporation in vacuo, the residue was diluted with ethyl acetate, washed with saturated sodium bicarbonate, dried (Na2SO4), carbon treated, the solution evaporated and passed through a silica gel column, eluting with hexane to yield 1.45 g of the title compound as an oil. The structure was verified by 1H-NMR spectroscopy.

Workup

  1. waitat 0° C. for one hour
  2. customquenched by addition of 4.1 ml acetic acid
  3. customThe solvents were evaporated in vacuo
  4. additionthe residual white gel diluted with 250 ml ethyl acetate
  5. washwashed with 1N hydrochloric acid (100 ml), saturated sodium bicarbonate solution
  6. dry with materialdried (Na2SO4)
  7. customEvaporation of solvent
  8. customafforded an oil which
  9. temperaturethe mixture heated
  10. temperatureat reflux for 16 hours
  11. customAfter evaporation in vacuo
  12. additionthe residue was diluted with ethyl acetate
  13. washwashed with saturated sodium bicarbonate
  14. dry with materialdried (Na2SO4), carbon
  15. additiontreated
  16. customthe solution evaporated
  17. washeluting with hexane

Sources & evidence

ORD record
ord-3f76ef17bb9a4f78b72ccfceeb4f9cd3
Source dataset
uspto-grants-1987_10
Patent number
US04703052

Reaction notes

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