Hydrochloric Acid → 2,6-Difluorobenzene-1-carbothioamide

HRID 2228439Notes

Reaction equation

HRID 2228439 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[C:4]#[N:5].C(N(CC)CC)C.O.[S-2:19].[Na+].[Na+].Cl>N1C=CC=CC=1>[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[C:4](=[S:19])[NH2:5]

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 8471TriethylamineHCID 746952,6-DifluorobenzonitrileHCID 19906495Sodium sulfide monohydrate

Product 1

HCID 126832122,6-Difluorobenzene-1-carbothioamideYield 76%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Into a 3 L three necked round bottom flask equipped with a mechanical stirrer, dry ice condenser, dropping funnel, and outlet to a trap filled with bleach was added pyridine (550 mL), 2,6-difluorobenzonitrile (208 g, 1.50 mol), triethylamine (202 g, 279 mL, 2.0 mol), and sodium sulfide hydrate (521 g, 2.17 mol-broken into pieces small enough to fit into the flask). The temperature of the stirred mixture was lowered to approximately 5° C. and to the slurry was added dropwise concentrated hydrochloric acid (143 g, 288 mL, 3.99 mol). An exotherm was noted and the rate of addition of the hydrochloric acid was such that the temperature of the reaction mixture did not exceed 25° C. for a total addition time of 75 min. The cooling bath was removed and the slurry was allowed to warm to RT and to stir over night. The mixture was poured into water (2 L) and was extracted with ether (3×500 mL). The ether layer was washed with dilute sulfuric acid, water, brine, dried (MgSO4), and the solvent removed in vacuo to give 232 grams of crude product. The starting material was removed from the product via kugelrohr distillation to give 197 g (76%) of 2,6-difluorobenzenethioamide. This material was used without further purification.

Workup

  1. additionfilled with bleach
  2. customwas lowered to approximately 5° C. and to the slurry
  3. customdid not exceed 25° C. for a total addition time of 75 min
  4. customThe cooling bath was removed
  5. additionThe mixture was poured into water (2 L)
  6. extractionwas extracted with ether (3×500 mL)
  7. washThe ether layer was washed with dilute sulfuric acid, water, brine
  8. dry with materialdried (MgSO4)
  9. customthe solvent removed in vacuo
  10. customto give 232 grams of crude product
  11. customThe starting material was removed from the product via kugelrohr distillation

Sources & evidence

ORD record
ord-be3dace2d8fb4ae897ce880798f738e8
Source dataset
uspto-grants-2002_07
Patent number
US06417187B2

Reaction notes

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