Pyridine → 2-[(2-Chlorophenyl)methyl]-4,4-dimethylisoxazolidine-5-one-3-thione

HRID 1155469Notes

Reaction equation

HRID 1155469 reaction equation
N1C=CC=CC=1.[CH3:7][C:8]([CH3:15])([C:12](Cl)=[O:13])[C:9](Cl)=[S:10].[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH2:23][NH:24][OH:25]>C(Cl)Cl>[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH2:23][N:24]1[C:9](=[S:10])[C:8]([CH3:15])([CH3:7])[C:12](=[O:13])[O:25]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 12715961Dimethylthiomalonyl chlorideHCID 12811040N-(2-ChlorobenZyl)hydroxylamine

Product 1

HCID 205605342-[(2-Chlorophenyl)methyl]-4,4-dimethylisoxazolidine-5-one-3-thioneYield 32.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-40 °C

Procedure

A stirred solution of 9.5 grams (0.12 mole) of pyridine in 170 ml of methylene chloride under an argon atmosphere was cooled to -10° C. and a solution of 11.1 grams (0.06 mole) of dimethylthiomalonyl chloride in 30 ml of methylene chloride was added slowly. The reaction mixture was cooled to -40° C. and 9.5 grams (0.06 mole) of N-(2-chlorophenylmethyl)hydroxylamine was added in one portion. The addition caused the reaction mixture temperature to quickly rise to -20° C. The reaction mixture was stirred at -20° C. for one hour, then was diluted with 150 ml of methylene chloride. The solution was washed with 100 ml of water, two portions of 75 ml each of aqueous 2 N hydrochloric acid, and finally, 50 ml of water. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. The oil was purified by column chromatography using 450 grams of silica gel. Elution was accomplished with chloroform. Early fractions from the chromatography yielded 5.3 grams of 2-[(2-chlorophenyl)methyl]-4,4-dimethylisoxazolidine-5-one-3-thione; mp 51°-53° C. Later fractions were combined to give 2.2 grams of 2-[(2-chlorophenyl)methyl]-4,4-dimethylisoxazolidine-3-one-5-thione as an oil. The nmr and the ir spectra were consistent with the proposed structure.

Workup

  1. additionThe addition
  2. customto quickly rise to -20° C
  3. washThe solution was washed with 100 ml of water, two portions of 75 ml each of aqueous 2 N hydrochloric acid
  4. dry with materialThe organic layer was dried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure to a residual oil
  7. customThe oil was purified by column chromatography
  8. washElution

Sources & evidence

ORD record
ord-edc0227f333240d6a8994d7051f19641
Source dataset
uspto-grants-1981_11
Patent number
US04302238

Reaction notes

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