Estudio sintético de aminales asimétricos derivados de rac-1,2-propanodiamina
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En este trabajo se estudió la síntesis del aminal quiral cíclico 4,9-dimetil-1,3,6,8-tetrazatriciclo[4.4.1.13,8]dodecano (DMTATD), el cual se obtuvo a partir de rac-1,2-propanodiamina y paraformaldehido en medio acuoso. Este aminal fue caracterizado completamente por métodos espectroscópicos (RMN-1H, RMN-13C, RMN bidimensional y FT-IR) y HR-ESI-MS. Se demostró que la configuración absoluta de sus centros quirales es 4R y 9S y es una molécula que constituye el caso único de un adamanzano que combina quiralidad central con quiralidad axial. Por otro lado, se ensayó la reactividad de este aminal frente a electrófilos, reaccionando fácilmente con el ion nitrosonio debido a su carácter de nucleófilo duro. Sin embargo, no reaccionó con sales de diazonio, ya que éstas presentan menos dureza que el ion nitrosonio. El producto de reacción con ácido nitroso fue 4-metil-1,3-dinitrosoimidazolidina, el cual se obtuvo como mezcla de seis rotámeros y su composición fue estudiada por RMN-1H y cálculos computacionales. Estos últimos mostraron que la estabilidad relativa de los rotámeros depende de la hiperconjugación del grupo N-N=O y en menor medida por la presencia de interacciones no covalentes débiles. DMTATD reaccionó con fenoles p-sustituídos, generando en un caso una base di-Mannich del tipo 2,2’-[metilimidazolidin-1,3-diil)dimetano-diil]bis(4-clorofenol) a través de una reacción de orto-aminometilación regioselectiva. Con un fenol m-sustituido formó benzoxazinas del tipo 3,3'-(propano-1,2-diil)bis(5,6,7-trisustituido-3,4-dihidro-2H-benzo[e][1,3]oxazina). Con nucleófilos más fuertes como β-naftol y 1H-benzotriazol no generó producto de aminometilación.
Abstract: In this work, the synthesis of cyclic chiral aminal 4,9-dimethyl-1,3,6,8-tetraazatricyclo [4.4.1.13,8]dodecane (DMTATD) was studied, which was obtained from rac-1,2-propanediamine and paraformaldehyde in aqueous medium. This aminal was fully characterized by spectroscopic methods (1H-NMR, 13C-NMR, two-dimensional NMR and FT-IR) and HR-ESI-MS. It was shown that the absolute configuration of its chiral centers is 4R and 9S and this molecule is the unique case of an adamanzane that combines central chirality with axial chirality. On the other hand, the reactivity of this aminal was tasted using electrophiles reagents at which it reacted easily with the nitrosonium ion due to its character as hard nucleophile. However, it did not react with diazonium salts, since these have less hardness than the nitrosonium ion. The product obtained from the reaction with nitrous acid was 4-methyl-1,3-dinitrosoimidazolidine, which was got as a mixture of six rotamers and its composition was studied by 1H-NMR and computational calculations. The latter showed that the relative stability of the rotamers depends on the hyperconjugation of the N-N=O group and to a lesser extent on the presence of weak non-covalent interactions. DMTATD reacted with p-substituted phenols, generating in one case a di-Mannich base consisting of 2,2´-[(4-methylimidazolidine-1,3-diyl)dimethane-diyl]bis(4-chlorophenol) through a reaction of regioselective ortho-aminomethylation. With a m-substituted phenol it formed benzoxazines of the type 3,3'-(propane-1,2-diyl)bis(5,6,7-trisubstituted-3,4-dihydro-2H-benzo[e][1,3]oxazine). With stronger nucleophiles such as β-naphthol and 1H-benzotriazole did not generate aminomethylation product.
Abstract: In this work, the synthesis of cyclic chiral aminal 4,9-dimethyl-1,3,6,8-tetraazatricyclo [4.4.1.13,8]dodecane (DMTATD) was studied, which was obtained from rac-1,2-propanediamine and paraformaldehyde in aqueous medium. This aminal was fully characterized by spectroscopic methods (1H-NMR, 13C-NMR, two-dimensional NMR and FT-IR) and HR-ESI-MS. It was shown that the absolute configuration of its chiral centers is 4R and 9S and this molecule is the unique case of an adamanzane that combines central chirality with axial chirality. On the other hand, the reactivity of this aminal was tasted using electrophiles reagents at which it reacted easily with the nitrosonium ion due to its character as hard nucleophile. However, it did not react with diazonium salts, since these have less hardness than the nitrosonium ion. The product obtained from the reaction with nitrous acid was 4-methyl-1,3-dinitrosoimidazolidine, which was got as a mixture of six rotamers and its composition was studied by 1H-NMR and computational calculations. The latter showed that the relative stability of the rotamers depends on the hyperconjugation of the N-N=O group and to a lesser extent on the presence of weak non-covalent interactions. DMTATD reacted with p-substituted phenols, generating in one case a di-Mannich base consisting of 2,2´-[(4-methylimidazolidine-1,3-diyl)dimethane-diyl]bis(4-chlorophenol) through a reaction of regioselective ortho-aminomethylation. With a m-substituted phenol it formed benzoxazines of the type 3,3'-(propane-1,2-diyl)bis(5,6,7-trisubstituted-3,4-dihydro-2H-benzo[e][1,3]oxazine). With stronger nucleophiles such as β-naphthol and 1H-benzotriazole did not generate aminomethylation product.