Efficient One-Pot Synthesis of Thiazol-2-imine Derivatives through Regioselective Reaction Between Primary Amines, Phenylisothiocyanate, and α-Chloroacetaldehyde.
OBJECTIVE
Thiazol-2-imine derivatives are interested for their pharmaceutical and biologic activities. A literature survey reveals that there have been no any reports on the synthesis of thiazol-2-imine derivatives without substituents in position C-4 and C-5 via one-pot reaction. Herein we report an efficient one-pot route for synthesis of these compounds in good to high yields.


METHODS
To a stirred mixture of amine (1 mmol) and phenylisothiocyanate (1 mmol) in EtOH (2 ml), KI (0.1 mmol) and DABCO (0.2 mmol) were added under reflux condition. Then α- chloroacetaldehyde (2 mmol) was added drop wise to the reaction mixture. After completion of the reaction, the product was purified over a silica gel short column (EtOAc/n-Hexane, 1:9).


RESULTS
One pot reaction of primary amine, phenylisocyanate, and α-chloroacetaldehyde was carried out in the presence of various base and KI in different solvents. It was found that the maximum yield was obtained when the temperature reaches to the boiling point of EtOH. Comparing the reaction results in EtOH, CH3CN, THF, CH2Cl2, and H2O at reflux in the presence of various base, demonstrate that the yield of reaction in EtOH in the presence of DABCO was the most effective. When the reaction runs at the 20 mol% of the DABCO and 10 mol% of the KI, the yield and the time of the reaction were excellent.


CONCLUSIONS
One-pot procedure can be used for the synthesis of thiazol-2-imine derivatives via the reaction of primary amines, α-chloroacetaldehyde, and phenylisothiocyanate in the presence of a catalytic amount of DABCO and potassium iodide in ethanol.
Department of Applied Chemistry, Faculty of Science, University of Mohaghegh Ardabili, P.O. Box 56199-11367, Ardabil. Iran.
Farough
F
Nasiri
Leila
L
Sabahi-Agabager
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D007097:Imines / Q000138:chemical synthesis* / Q000737:chemistry; D017953:Isocyanates / Q000138:chemical synthesis / Q000737:chemistry*; D017879:Isothiocyanates / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry; D013890:Thiourea / Q000031:analogs & derivatives / Q000138:chemical synthesis
D007097:Imines; D017953:Isocyanates; D017879:Isothiocyanates; D013844:Thiazoles; C005441:phenylisothiocyanate; C025319:phenyl isocyanate; C004656:chloroacetaldehyde; D000079:Acetaldehyde; D013890:Thiourea
1; 3-disubstituted thiourea; one-pot reaction; thiazol-2-imine; α-Chloroacetaldehyde