Flow Synthesis of 2-[Methyl(pyridin-2-yl)amino]ethanol: An Experimental and Computational Study

Author(s)

Cuesta Calvo, Paulo Victor ^[1] ; Batista, Patrick Rodrigues ^[2] ; de Oliveira Silva, Renan Rodrigues ^[1] ; Converti, Attilio ^[3] ; Al Arni, Saleh ^[4] ; Solisio, Carlo ^[3] ; Ducati, Lucas C. ^[2] ; Alves Palma, Mauri Sergio ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Av Prof Lineu Prestes, 580 Butanta, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Chem, Av Prof Lineu Prestes, 748 Butanta, BR-05508000 Sao Paulo, SP - Brazil

^[3] Univ Genoa, Dept Civil Chem & Environm Engn, Via Opera Pia 15, I-16145 Genoa - Italy

^[4] Univ Hail, Coll Engn, Dept Chem Engn, POB 2440, Hail 81441 - Saudi Arabia

• Document type: Journal article
• Source: CHEMICAL ENGINEERING & TECHNOLOGY; v. 44, n. 2 DEC 2020.
• Web of Science Citations: 0

Abstract

Microreactor technology is increasingly applied in the chemical-pharmaceutical industry for safer and more efficient drug production as compared to the traditional batch process. This technology is employed for the first time to study the production of 2-{[}methyl(pyridin-2-yl)amino]ethanol, the first intermediate in rosiglitazone synthesis. Under the optimum operating conditions, a single microreactor chip at 160 degrees C allowed to produce the equivalent of more than five batch reactors at 120 degrees C. The kinetic study indicated that the reaction is second order. Thermodynamic parameters were determined by the Eyring equation and density functional theory (DFT) calculations with good agreement. DFT results suggested a concerted nucleophilic aromatic substitution reaction mechanism. (AU)

• FAPESP's process: 18/07308-4 - Effect of solvent on shielding tensor and coupling constant calculations of platinum (iii) dinuclear complexes via ab initio molecular dynamics
• Grantee: Patrick Rodrigues Batista
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/12830-9 - Synthesis of Pioglitazone, Rosiglitazone and Lobeglitazone in continuous flow in capillary microreactors
• Grantee: Mauri Sergio Alves Palma
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/26717-2 - Rosiglitazone synthetic route development in batch process and capillary microreactor
• Grantee: Paulo Victor Cuesta Calvo
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/10246-0 - Nuclear magnetic resonance spectroscopy: from pulse sequences to structural assignments
• Grantee: Claudio Francisco Tormena
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/01478-5 - Synthesis of pioglitazone in batch and capillary microreactor
• Grantee: Renan Rodrigues de Oliveira Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/17750-3 - Solvent Effect in NMR Parameters by ab initio Molecular Dynamics
• Grantee: Lucas Colucci Ducati
• Support Opportunities: Regular Research Grants