TY - JOUR
T1 - A rapid and efficient microwave-assisted synthesis of hydantoins and thiohydantoins
AU - Muccioli, Giulio G.
AU - Poupaert, Jacques H.
AU - Wouters, Johan
AU - Norberg, Bernadette
AU - Poppitz, Wolfgang
AU - Scriba, Gerhard K E
AU - Lambert, Didier M.
PY - 2003/2/17
Y1 - 2003/2/17
N2 - The present paper describes studies on the synthesis of the antiepileptic drug phenytoin, and of structurally related derivatives. First, the influence of the solvent has been investigated in the microwave-assisted synthesis of the drug, resulting in a yield improvement and a cleaner reaction. Second, a two-step reaction is described to synthesize selectively and in high yields phenytoin. The first step consists in microwave activation of the reaction of benzil with thiourea, the second step includes the conversion of the resulting 2-thiohydantoin to phenytoin using hydrogen peroxide. Moreover, microwave activation is a very convenient method for the synthesis of 3-alkylated phenytoin derivatives, resulting in a much more selective method than the previously reported procedure using alkylating agents.
AB - The present paper describes studies on the synthesis of the antiepileptic drug phenytoin, and of structurally related derivatives. First, the influence of the solvent has been investigated in the microwave-assisted synthesis of the drug, resulting in a yield improvement and a cleaner reaction. Second, a two-step reaction is described to synthesize selectively and in high yields phenytoin. The first step consists in microwave activation of the reaction of benzil with thiourea, the second step includes the conversion of the resulting 2-thiohydantoin to phenytoin using hydrogen peroxide. Moreover, microwave activation is a very convenient method for the synthesis of 3-alkylated phenytoin derivatives, resulting in a much more selective method than the previously reported procedure using alkylating agents.
KW - 5-aryl-3-alkyl-imidazolidinediones
KW - Microwave activation
KW - Phenytoin
UR - http://www.scopus.com/inward/record.url?scp=0037450446&partnerID=8YFLogxK
U2 - 10.1016/S0040-4020(03)00033-4
DO - 10.1016/S0040-4020(03)00033-4
M3 - Article
AN - SCOPUS:0037450446
SN - 0040-4020
VL - 59
SP - 1301
EP - 1307
JO - Tetrahedron
JF - Tetrahedron
IS - 8
ER -