Toluene → 2-Bromo-5-(chloromethyl)pyridine

HRID 37359Notes

Reaction equation

HRID 37359 reaction equation
S(Cl)([Cl:3])=O.O[CH2:6][C:7]1[CH:8]=[N:9][C:10]([Br:13])=[CH:11][CH:12]=1.[OH-].[Na+].C1(C)C=CC=CC=1>C(#N)C.O>[Cl:3][CH2:6][C:7]1[CH:8]=[N:9][C:10]([Br:13])=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 64212496-Bromo-3-pyridinemethanol

Product 1

HCID 64246582-Bromo-5-(chloromethyl)pyridineYield 134%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Procedure

To a mechanically-stirred solution of 78.12 g of thionyl chloride in 450 mL of acetonitrile at 15° C. was added a solution of 160.75 g of 3-hydroxymethyl-6-bromopyridine in 446 mL of acetonitrile over 30 minutes. The temperature rose to 22° C. during the addition, and the reaction mixture was stirred for 15 minutes at room temperature. The mixture was cooled in an ice bath, and a solution of 70 g of NaOH in 1.4 L of water was added at such a rate that the temperature did not exceed 15° C. 603 mL of toluene was added to the mixture and stirred rapidly. The layers were separated. The aqueous phase was reextracted with toluene. The combined organic phase was concentrated in vacuo to give 181.61 g of 3-chloromethyl-6-bromopyridine.

Workup

  1. additionThe temperature rose to 22° C. during the addition
  2. temperatureThe mixture was cooled in an ice bath
  3. customdid not exceed 15° C
  4. stirringstirred rapidly
  5. customThe layers were separated
  6. concentrationThe combined organic phase was concentrated in vacuo

Sources & evidence

ORD record
ord-9a8cc4f9960f4607baafb2e96f52d3be
Source dataset
uspto-grants-1995_05
Patent number
US05420270

Reaction notes

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