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

HRID 904408Notes

Reaction equation

HRID 904408 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

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 starting for 2 hours at 0°, 3-bromoethylisothiazole (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 as eluant gave N-methyl-N'-[2-(3-isothiazolylmethylthio)ethyl]thiourea. (Found: C, 38.9; H, 5.4; N, 16.5; S, 38.3. C8H13N3S3 requires: C, 38.8; H, 5.3; N, 17.0; S, 38.9).

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-4db84228be884952840fa3ab5add2e1b
Source dataset
uspto-grants-1980_10
Patent number
US04230865

Reaction notes

Loading…