Methyl isothiocyanate → N-Methyl-N'-(2-{[(1,2-thiazol-3-yl)methyl]sulfanyl}ethyl)thiourea

HRID 1974414Notes

Reaction equation

HRID 1974414 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][S:5][CH2:6][C:7]1[CH:11]=[CH:10][S:9][N:8]=1.[CH3:12][N:13]=[C:14]=[S:15]>C(O)C>[CH3:12][NH:13][C:14]([NH:2][CH2:3][CH2:4][S:5][CH2:6][C:7]1[CH:11]=[CH:10][S:9][N:8]=1)=[S:15]

Participants

4

Reactant 2

HCID 11167Methyl isothiocyanateHCID 205502093-[(2-Aminoethyl)thiomethyl]isothiazole hydrochloride

Product 1

HCID 20466672N-Methyl-N'-(2-{[(1,2-thiazol-3-yl)methyl]sulfanyl}ethyl)thiourea

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(i) A solution was prepared by the gradual addition of cysteamine hydrochloride (2.03 g) to sodium (0.83 g) dissolved in ethanol (50 ml) with stirring at 0° under a nitrogen atmosphere. After stirring for 2 hours at 0°, 3-bromomethylisothiazole (3.2 g) was added dropwise over 15 minutes at 0°, the reaction mixture subsequently being set aside overnight at room temperature. Following acidification to pH 3.5 with hydrochloric acid, concentration and re-evaporation with ethanol, the residue was dissolved in ethanol, filtered and concentrated to yield 3-[(2-aminoethyl)thiomethyl]isothiazole hydrochloride (3.5 g). This was converted directly to the free base by treatment with aqueous potassium carbonate and extraction with ether. The extracts were dried over magnesium sulphate, filtered and concentrated to yield the amine base as an oil (1.56 g). The amine was dissolved in ethanol (10 ml), methyl isothiocyanate (0.66 g) added, and the solution heated under reflux for 30 minutes. Concentration, followed by purification of the crude product by chromatography on a column of silica gel with ethyl acetate as eluant followed by chromatography on a column of alumina with benzene/ethyl acetate gave N-methyl-N' -[2-(3-isothiazolylmethylthio)ethyl]-thiourea.

Workup

  1. extractionThis was converted directly to the free base by treatment with aqueous potassium carbonate and extraction with ether
  2. dry with materialThe extracts were dried over magnesium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto yield the amine base as an oil (1.56 g)
  6. temperaturethe solution heated
  7. temperatureunder reflux for 30 minutes
  8. concentrationConcentration
  9. customfollowed by purification of the crude product by chromatography on a column of silica gel with ethyl acetate as eluant

Sources & evidence

ORD record
ord-f219bbf6afde4a92b08902f218ded4bb
Source dataset
uspto-grants-1976_12
Patent number
US04000302

Reaction notes

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