Synthesis of Methyl-2[N-subtituted-N-(2-hydroxyethyl)]amino-2-hydroxyacetates and 2-Hydroxy-4-alkylperhydro-1,4-oxazin-3-ones
Teresa Mancilla Percino* and Teresita Rocío Cruz Hernández
Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apdo. Postal 14740, 07000 México, D. F., México. tmancill@cinvestav.mx
Recibido 7 de agosto de 2007 ]]> Aceptado el 20 de octubre de 2007
Abstract
This work describes the study of the reaction of methyl 2-hydroxy-2-methoxy acetate (1) with the β-amino alcohols, N-methylethanolamine (2), N-benzylethanolamine (3), (1R,2S)-(-)-ephedrine (4) and (1S,2S)-(+)-pseudoephedrine (5) in the presence of a mixture of benzene/ethanol and formic acid, and also without solvent. In the first case the reaction led to the new acyclic compounds methyl-2-[N-methyl-N-(2-hydroxyethyl)]amino-2-hydroxyacetate (2a), methyl-2[N-benzyl-N-(2-hydroxyethyl)]amino-2-hydroxyactetate (3a), methyl-2{N-methyl-N-[(2R,1S)-2-phenyl-1-methyl-2-hydroxyethyl]}amino-2-hydroxyacetates (4a, 4a') and methyl-2{N-methyl-N-[(2S,1S)-2-phenyl-1-methyl-2-hydroxyethyl]}amino-2-hydroxyacetates (5a, 5a'). The reaction without solvent led to cyclic compounds 2-hydroxy-4-methylperhydro-1,4-oxazin-3-ones (2b), 2- hydroxy-4-benzylperhydro-1,4-oxazin-3-one (3b), (2S,5S,6R)-2-hydroxy-4,5-dimethyl-6-phenylperhydro-1,4-oxazin-3-one (4b) and (2S,5S,6S)-2-hydroxy-4,5-dmiethyl-6-phenylperhydro-1,4-oxazin-3-one (5b), which we have been reported before, except 3b. The whole compounds were characterized by 1H, 13C, 15N (acyclic compounds) NMR, HETCOR, infrared and mass spectrometry. Determination of minimum energy of the preferred conformation was achieved for compounds 4a, 4a' , 5a and 5a' by theoretical calculation. The structures of 3b and 5b were further established by a single-crystal X-ray diffraction.
Key words: 2-(N-hydroxyethylamino)hydroxyacetates, Oxazin-3-ones, Morpholin-3-ones, β-aminoalcohols, Spectroscopy, X-ray.
Resumen
En este trabajo se describe el estudio de la reacción del 2-hidroxi-2-metoxiacetato de metilo (1) con los β-amino alcoholes: N-metiletanolamina (2), N-benciletanolamina (3), (1R,2S)-(-)-efedrina (4) y (1S,2S)-(+)-pseudoefedrina (5) en presencia de la mezcla de benceno/etanol y ácido fórmico, y también sin disolvente. En el primer caso la reacción conduce a los nuevos compuestos acíclicos metil-2-[N-metil-N-(2-hidroxietil)]amino-2-hidroxiacetato (2a), metil-2[N-bencil-N-(2-hidroxietil)]amino-2-hidroxiacetato (3a), metil-2{N-metil-N-[(2R,1S)-2-fenil-1-metil-2-hidroxietil]}amino-2-hidroxiacetatos (4a, 4a') y metil-2{N-metil-N-[(2S,1S)-2-fenil-1-metil-2-hidroxietil]}amino-2-hidroxiacetatos (5a, 5a'). La reacción sin disolvente conduce a los compuestos cíclicos 2-hidroxi-4-metilperhidro-1,4-oxazin-3-onas (2b), 2-hidroxi-4-bencilperhidro-1,4-oxazin-3-ona (3b), (2S,5S,6R)-2-hidroxi-4,5-dimetil-6-fenilperhidro-1,4-oxazin-3-ona (4b) y (2S,5S,6S)-2-hidroxi-4,5-dimetil-6-fenilperhidro-1,4-oxazin-3-ona (5b), los cuales han sido reportados por nosotros anteriormente, excepto 3b. Todos los compuestos fueron caracterizados por RMN de 1H, 13C y 15N (compuestos acíclicos), HETCOR, infrarrojo y espectrometría de masas. Además, se llevó a cabo la determinación de la energía mínima de la conformación preferida de los compuestos 4a, 4a', 5a y 5a' a partir de cálculos teóricos. Las estructuras de 3b y 5b fueron además establecidas por difracción de rayos-X.
Palabras clave: 2-(N-hidroxietilamino)hidroxiacetates, Oxazin-3-onas, Morfolin-3-onas, β-Aminoalcoholes, Espectroscopia, Rayos-X.
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