TY - JOUR
T1 - Isothioureas, ureas, and their N-methyl amides from 2-aminobenzothiazole and chiral amino acids
AU - Padilla-Martínez, Itzia I.
AU - González-Encarnación, José Miguel
AU - García-Báez, Efrén V.
AU - Cruz, Alejandro
AU - Ramos-Organillo, Ángel Andrés
N1 - Publisher Copyright:
© 2019 by the authors.
PY - 2019/9/18
Y1 - 2019/9/18
N2 - In this investigation, the reaction of 2-dithiomethylcarboimidatebenzothiazole with a series of six chiral amino-acids was studied. The reaction proceeds through the isolable sodium salt of SMe-isothiourea carboxylates as intermediates, whose reaction with methyl iodide in stirring DMF as solvent affords SMe-isothiourea methyl esters. The presence of water in the reaction leads to the corresponding urea carboxylates as isolable intermediates, whose methyl esters were obtained. Finally, the urea N-methyl amide derivatives were isolated when SMe-isothiourea or urea methyl esters were reacted with methylamine in the presence of water. The structures of synthesized compounds were established by 1H and 13C nuclear magnetic resonance and the structures of SMe-isothiourea methyl esters derived from (l)-glycine, (l)-alanine, (l)-phenylglycine, and (l)-leucine, by X-ray diffraction analysis. This methodology allows to functionalize 2-aminobenzothiazole with SMe-isothiourea, urea, and methylamide groups derived from chiral amino acids to get benzothiazole derivatives containing coordination sites and hydrogen bonding groups. Further research on the biological activities of some of these derivatives is ongoing.
AB - In this investigation, the reaction of 2-dithiomethylcarboimidatebenzothiazole with a series of six chiral amino-acids was studied. The reaction proceeds through the isolable sodium salt of SMe-isothiourea carboxylates as intermediates, whose reaction with methyl iodide in stirring DMF as solvent affords SMe-isothiourea methyl esters. The presence of water in the reaction leads to the corresponding urea carboxylates as isolable intermediates, whose methyl esters were obtained. Finally, the urea N-methyl amide derivatives were isolated when SMe-isothiourea or urea methyl esters were reacted with methylamine in the presence of water. The structures of synthesized compounds were established by 1H and 13C nuclear magnetic resonance and the structures of SMe-isothiourea methyl esters derived from (l)-glycine, (l)-alanine, (l)-phenylglycine, and (l)-leucine, by X-ray diffraction analysis. This methodology allows to functionalize 2-aminobenzothiazole with SMe-isothiourea, urea, and methylamide groups derived from chiral amino acids to get benzothiazole derivatives containing coordination sites and hydrogen bonding groups. Further research on the biological activities of some of these derivatives is ongoing.
KW - 2-aminobenzothiazole
KW - 2-dithiomethylcarboimidatebenzothiazole
KW - S-methyl-isothioureas
KW - Urea N-methyl amides
KW - Urea-carboxylate methyl esters
KW - α-amino-acids
UR - http://www.scopus.com/inward/record.url?scp=85072518034&partnerID=8YFLogxK
U2 - 10.3390/molecules24183391
DO - 10.3390/molecules24183391
M3 - Artículo
C2 - 31540462
AN - SCOPUS:85072518034
SN - 1420-3049
VL - 24
JO - Molecules
JF - Molecules
IS - 18
M1 - 3391
ER -