Hydrochloric Acid → [4-(Chloromethyl)phenyl]methanol

HRID 1683464Notes

Reaction equation

HRID 1683464 reaction equation
[C:1]1([CH2:9][OH:10])[CH:6]=[CH:5][C:4]([CH2:7]O)=[CH:3][CH:2]=1.S(Cl)([Cl:13])=O.C(=O)(O)[O-].[Na+].Cl>C(Cl)(Cl)Cl>[OH:10][CH2:9][C:1]1[CH:6]=[CH:5][C:4]([CH2:7][Cl:13])=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 115061,4-BenzenedimethanolHCID 24386Thionyl ChlorideHCID 516892Sodium Bicarbonate

Product 1

HCID 5107660[4-(Chloromethyl)phenyl]methanolYield 75%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Conditions

Temperature
0 °C

Procedure

1,4-benzenedimethanol (13.8 g, 0.10 mole) was dispersed in chloroform (100 mL) in a 500 mL three-neck round bottom flask equipped with a magnetic stirring bar, an addition funnel, a nitrogen inlet and a gas scrubber. The mixture was cooled to 0° C. in an ice bath. Thionyl chloride (13.1 g, 0.11 mole) dissolved in chloroform (10 mL) was added dropwise over ten minutes with rapid stirring to the cooled mixture. As the addition proceeded, the mixture largely cleared. During the addition step, and for one hour thereafter, the reaction flask was swept with nitrogen which was then passed through the scrubber before venting to the atmosphere. The nitrogen was turned off and the scrubber disconnected. The mixture was allowed to come to room temperature and stirring was continued for 20 hours. Sufficient sodium bicarbonate was added to neutralize any residual hydrogen chloride. The mixture was filtered through a coarse glass frit and the solvent removed under reduced pressure at 35° C. A sample of the residue was chromatographed on silica gel (200 g) with an ethyl acetate:hexane (2:3) solvent. p-Hydroxymethyl-benzyl chloride was obtained in 75% yield (11.64 g). The product had a melting point of 58°-60° C. NMR spectral data were as follows: 1H NMR (CDCl3, 300 MHz): δ7.3 (m, 4H), 4.70 (s, 2H), 4.59 (s, 2H), 1.67 (s, 1H); 13C NMR (CDCl3, 75 MHz, ppm) 141.372, 135.995, 128.876, 127.366, 64.927, 46.121.

Workup

  1. customequipped with a magnetic stirring bar, an addition funnel, a nitrogen inlet
  2. additionwas added dropwise over ten minutes
  3. additionAs the addition
  4. additionDuring the addition step
  5. customto come to room temperature
  6. stirringstirring
  7. waitwas continued for 20 hours
  8. filtrationThe mixture was filtered through a coarse glass frit
  9. customthe solvent removed under reduced pressure at 35° C
  10. customA sample of the residue was chromatographed on silica gel (200 g) with an ethyl acetate:hexane (2:3) solvent

Sources & evidence

ORD record
ord-88eb4d77fde84462b0c8250eddd4253c
Source dataset
uspto-grants-1997_06
Patent number
US05637780

Reaction notes

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