Antonio Guirado

A theoretical study of topomerization of imine systems: Inversion, rotation or mixed mechanisms?

The different mechanisms, rotation, inversion, or intermediate mechanism, by which occur the topomerization of imine systems R2 CNX have been studied by applying ab initio, B3LYP, and MP2 methods. The effect of a wide variety of substituents R and X on the isomerization pathway have been examined by computing fully optimized structures of the ground and transition states (136 isomers belonging to different imine families were studied and more than 300 transition structures were determined at various levels of theory). Energy barriers have been also obtained and it was found that the groups R and X have a strong influence on the type of mechanism involved and the activation energies. Thus, and depending on the type of substituents, transition state structures related to the following kinds of processes were found: pure inversion, intermediate mechanisms, rotation, and enhanced rotation (hyper‐rotation). In turn, the corresponding activation energies range between very low (<10 kcal/mol) and extremely high (> 70 kcal/mol) values. A simple index that allows us to quantify the percentage of inversion or rotation mechanism is proposed.

Electrochemical reduction of diaryl-1,2-diketones in the presence of carbonimidoyl dichlorides. A new method for the synthesis of enediol iminocarbonates

Abstract Selective cathodic reduction of diaryl-1,2-diketones in the presence of carbonimidoyl dichlorides provides a new and very convenient method for the synthesis of the title compounds.

Synthesis and biological evaluation of 4-alkoxy-6,9-dichloro[1,2,4]triazolo[4,3-a]quinoxalines as inhibitors of TNF-α and IL-6

An efficient synthetic method for previously unattainable 4-alkoxy-6,9-dichloro[1,2,4]triazolo[4,3-a]quinoxalines has been established. Reactions between 5,8-dichloro-2,3-dicyanoquinoxaline and alcohols in the presence of triethylamine led to 3-alkoxy-5,8-dichloro-2-cyanoquinoxalines in high to quantitative yields. These compounds were treated with hydrazine giving 3-alkoxy-5,8-dichloro-2-hydrazinoquinoxalines in near quantitative yields, that reacted with triethyl orthoformate to provide the title compounds in high yields. The molecular structure of a member of this family of compounds: 6,9-dichloro-4-ethoxy[1,2,4]triazolo[4,3-a]quinoxaline, was determined by X-ray crystallography. The series of compounds synthesized were evaluated for their potential anti-inflammatory activity as inhibitors of the pro-inflammatory cytokines TNF-α and IL-6. Compounds 8e, 8a, 8b and 8g presented simultaneously good levels of inhibition of both cytokines being compound 8e the most concomitantly potent one. Compounds 8d, 8f and 8h specifically inhibited IL-6 with no significant inhibition of TNF-α. Compound 8c was not significantly active upon TNF-α, and showed no activity upon IL-6.

Direct conversion of 4-amino-2-phenyl-2-oxazolines into either 2-arylimino-1,3-oxazolidine or 2-arylimino-1,3-thiazolidine hydrochlorides

Abstract A novel heterocycle–heterocycle inter-conversion is reported. It enables direct and efficient syntheses of either polysubstituted 2-arylimino-1,3-oxazolidine or 2-arylimino-1,3-thiazolidine hydrochlorides by a one-pot treatment of 4-amino-2-phenyl-2-oxazolines with arylisocyanates or arylisothiocyanates, respectively, followed by addition of hydrochloric acid.

One-Pot Synthesis of 1,4-Dichlorophenazines

Abstract An efficient, generally applicable one-pot method for the synthesis of 1,4-dichlorophenazines has been established. The method is based on the use of 3,3,6,6-tetrachloro-1,2-cyclohexanedione 2 as a synthetic equivalent of 3,6-dichloro-1,2-benzoquinone 1. The reaction of 2 with primary 1,2-arylidenediamines followed by treatment with pyridine provides the title compounds in nearly quantitative yields. 1,1,4,4-Tetrachloro-1,2,3,4-tetrahydrophenazines are isolable intermediates. The crystallographic X-ray structure of 7,7′-Bis(1,1,4,4-tetrachloro-1,2,3,4-tetrahydrophenazine) 7 has been determined.

Cathodic reduction of aromatic halides. an evidence for an ionic mechanism

Abstract A study on the cathodic reduction of the C-X bond in aryl vicinal dihalides and monohalides is made, demostrating in an unequivocal way the presence in all the cases of aryl anion intermediates.

Electrochemical generation of 4-amino-2-aryl-2-oxazolines

A convenient method for the synthesis of the title compounds has been established. Chloralbenzamides were efficiently converted to N-(1-amino-2,2-dichloroethyl)benzamides which were directly transformed to 4-amino-2-aryl-2-oxazolines in fair to good yields by electrochemical reduction in an aprotic medium under constant cathodic potential. The molecular structure of the electrolysis products has been corroborated by X-ray crystallographic analysis of 4-(1-benzyl-3-phenylureido)-2-phenyl-2-oxazoline.

Electrochemical generation of N-(2,2-dichlorovinyl)amides

Abstract A convenient method for the synthesis of N-(2,2-dichlorovinyl)amides has been established. Treatment of chloralamides with phosphorus pentachloride provides N-(1,2,2,2-tetrachloroethyl)amides in high yields whose electrochemical reduction leads to the title compounds in fair to quantitative yields. This approach exhibits superior efficiency and versatility than previously reported procedures.

A new synthetic route to 2-oxazolines. The electrochemical reduction of N-(2,2-dichloroethyl)amides as a key step

Abstract A convenient new method for the synthesis of 2-oxazolines has been established involving the preparation of N-(2,2-dichloroethyl)amides followed by electrochemical reductive cyclizations. It has been applied successfully in preparing previously unknown 4-alkylamino-2-phenyl-2-oxazolines in fair to good yields.

Electrochemical obtention of cis- and trans-3,6-dimethoxy-3,6-dimethyl-1,4-cyclohexadienes

Preparation par oxydation sur electrode de graphite du p-xylene dans le melange methanol-methanolate de sodium