Rodrigo Octavio Mendonça Alves de Souza

Continuous Flow Synthesis of α-Halo Ketones: Essential Building Blocks of Antiretroviral Agents

The development of a continuous flow process for the multistep synthesis of α-halo ketones starting from N-protected amino acids is described. The obtained α-halo ketones are chiral building blocks for the synthesis of HIV protease inhibitors, such as atazanavir and darunavir. The synthesis starts with the formation of a mixed anhydride in a first tubular reactor. The anhydride is subsequently combined with anhydrous diazomethane in a tube-in-tube reactor. The tube-in-tube reactor consists of an inner tube, made from a gas-permeable, hydrophobic material, enclosed in a thick-walled, impermeable outer tube. Diazomethane is generated in the inner tube in an aqueous medium, and anhydrous diazomethane subsequently diffuses through the permeable membrane into the outer chamber. The α-diazo ketone is produced from the mixed anhydride and diazomethane in the outer chamber, and the resulting diazo ketone is finally converted to the halo ketone with anhydrous ethereal hydrogen halide. This method eliminates the need to store, transport, or handle diazomethane and produces α-halo ketone building blocks in a multistep system without racemization in excellent yields. A fully continuous process allowed the synthesis of 1.84 g of α-chloro ketone from the respective N-protected amino acid within ~4.5 h (87% yield).

Photochemistry under Continuous Flow Conditions

Flow photochemistry is a growing field and has shown many interesting applications in the recent years due to the versatility of the technique related to the flexibility on the construction of the apparatus needed for the required transformation. The use of available materials and commercial source of light makes it an attractive option to several organic chemists who want to start exploring the fruitful field of photochemical reactions.

Continuous Flow Reactions: From Green Chemistry Towards a Green Process

Continuous flow reactions are an emerging technology in the synthesis of high value molecules, such as active pharmaceutical ingredients. Several of them are advantages of this technology, and in the present text that is presented in the context

β-C-ribosyl-1,2,3-triazole analogues of guanosine as potencial antiviral agents against dengue and hepatitis C virus

th Brazilian Meeting on Organic Synthesis – 15 th BMOS – November 10-13, 2013 Campos do Jordao, Brazil uf062-C-ribosyl-1,2,3-triazole analogues of guanosine as potencial antiviral agents against dengue and hepatitis C virus Alexandra Basilio Lopes, Nelilma Correia Romeiro, Amilcar Tanuri, Nadege LubinGermain, Rodrigo Octavio M. A. de Souza, Leandro S.M. Miranda § Federal University of Rio de Janeiro, BOSS Laboratory, † University of Cergy-Pontoise, SOSCO Laboratory, EA 4505, ≠ Federal University of Rio de Janeiro, Molecular Virology Laboratory, Federal University of Rio de Janeiro-Campus Macae Professor Aloisio Teixeira, LICC-Laboratorio Integrado de Computacao Cientifica

Synthesis of oxazolones under Dakin-West conditions

We proceeded the reaction using phenylalanine (520 mg; 3 mmol), chloroacetic anhydride (1,5 g; 9 mmol; 3 eq), methylimidazole (0,105 ml, 1,2 mmol; 0,5 eq) as the catalyst and dioxane as the solvent (5 ml). 2 The reaction was kept under reflux during 2 hours. Afterwards, water was added to hydrolyze the remaining anhydride. The organic layer was washed with saturated solution of potassium bicarbonate and water and then dried with anhydrous Na2SO4. After evaporation of the solvent, the product was recrystalized in a mixture of ethyl acetate and hexane (468 mg; 84% yield). Surprisingly, the espectroscopical data for the isolated product indicated the absence of methylene as well as the chlorine atom. A methyl group was observed in these analysis. These data correspond with the data reported for oxazolone 2 as the sole product of the reaction.