p-Bromochlorobenzene → [4-Bromo-2-(hydroxymethyl)phenyl](4-chlorophenyl)methanone

HRID 2163680Notes

Reaction equation

HRID 2163680 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][CH:3]=1.[Mg].[Br:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C:16](=[O:17])[O:15][CH2:14]2.[Cl-].[NH4+]>CCOCC.O1CCCC1>[OH:15][CH2:14][C:13]1[CH:12]=[C:11]([Br:10])[CH:20]=[CH:19][C:18]=1[C:16]([C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)=[O:17]

Participants

7

Reactant 4

HCID 7806p-BromochlorobenzeneHCID 25517Ammonium ChlorideHCID 6031445-BromophthalideHCID 5462224Magnesium

Product 1

HCID 22751307[4-Bromo-2-(hydroxymethyl)phenyl](4-chlorophenyl)methanoneYield 98.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A Grignard-solution prepared from 220 grams (1.15 mol) of p-chlorobromobenzene and 29 grams of magnesium turnings (1.2 mol) in 1500 milliliters of dry ether was added dropwise in the course of one hour to a suspension of 213 grams of 5-bromphthalide (1 mol) in 1500 milliliters of dry tetrahydrofuran. The temperature was not allowed to rise over 10 degrees Centigrade. After the addition was completed the reaction mixture was stirred for three hours at room temperature. The mixture was then poured into 2 liters of icewater and 100 milliliters of saturated aqueous ammonium chloride were added. The etherphase was separated and the water-tetrahydrofuranphase extracted once with 500 milliliters of ether. The etherphase was washed with water, dried over anhydrous magnesiumsulphate, filtered and evaporated in vacuum to yield 320 grams of 2-hydroxymethyl-4-bromo-4'-chloro-benzophenone in the form of a yellow oil which was not purified further but used directly in the next step. The 320 grams of oil were dissolved in 200 milliliters of dry tetrahydrofuran and added dropwise to a great excess of N,N-dimethylaminopropyl magnesium chloride in tetrahydrofuran under gentle reflux. After completed addition the mixture was refluxed over night. The reaction mixture was then poured into 5 liters of icewater and 200 milliliters of saturated aqueous ammonium chloride solution added. The mixture was extracted with a total of 2500 milliliters of ether. The etherphase was then extracted with 20% aqueous acetic acid to acid reaction, whereupon the acetic acid solution was made alkaline with 10 N sodiumhydroxide solution. After cooling, the oil, which separated out, was extracted twice with 500 milliliters of ether. The combined ether extracts were dried over anhydrous potassium carbonate, treated with active carbon and evaporated in vacuum. The remaining oil consists of somewhat impure (4-bromo-2-(hydroxymethyl)phenyl)-(4-chlorophenyl)-(3-dimethylaminopropyl)methanol which was used in the next step without further purification. Yield: 219 grams.

Workup

  1. customto rise over 10 degrees Centigrade
  2. additionAfter the addition
  3. additionwere added
  4. customThe etherphase was separated
  5. extractionthe water-tetrahydrofuranphase extracted once with 500 milliliters of ether
  6. washThe etherphase was washed with water
  7. dry with materialdried over anhydrous magnesiumsulphate
  8. filtrationfiltered
  9. customevaporated in vacuum

Sources & evidence

ORD record
ord-df52cf3b4d74445e88d5d65df01b78d2
Source dataset
uspto-grants-1979_01
Patent number
US04136193

Reaction notes

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