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

HRID 1721605Notes

Reaction equation

HRID 1721605 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-4b421fd078a84a14bab0d2da0427d926
Source dataset
uspto-grants-1996_04
Patent number
US05512561

Reaction notes

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