Carbon-nitrogen bond-forming reactions in supercritical and expanded-liquid carbon dioxide media : green synthetic chemistry with multiscale reaction and phase behavior modeling

The goal of this work was to develop a detailed understanding of carbon-nitrogen (C-N) bond-forming reactions of amines carried out in supercritical and expanded-liquid carbon dioxide (CO2) media. Key motivations behind this study were the importance of nitrogen-containing compounds in the pharmaceutical and fine chemical industries and a growing commercial interest in utilizing environmentally-friendly syntheses and processing with cost-efficient, green solvents. The thermodynamics and reaction engineering characteristics associated with the synthesis of several model C-N bond-forming reactions were examined both experimentally and theoretically. Operating conditions and engineering correlations were identified that will facilitate process scale-up and potential commercialization of these and other fundamentally-important CO2-based processes. Amine chemistry in CO2-based media was complicated by the facility of nucleophilic amines to react with carbon dioxide to form carbamic acids, which sometimes interfered with desired reaction pathways. Experimental observations and a complimentary ab initio quantum chemical calculation study revealed that carbamic acid formation was suppressed when adding bulky N-substituents to primary amines and when operating at low pressures and/or high temperatures. With a firm understanding of amine-CO2 chemistry, we developed a synthetic protocol that produced classes of pharmacologically-significant nitrogen heterocycles known as tetrahydroisoquinolines and tetrahyrdo-carbolines. Our method involved (1) the in situ carbamation of amines from their reaction with carbon dioxide and a dialkyl carbonate and (2) the Pictet-Spengler cyclization of these carbamates by their reaction with an aldehyde in the presence of acid. The conversion of amines to their carbamate derivatives offered suitable N-protection against carbamic acid formation.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2008

Author dc:creator

• Ciccolini, Rocco P

Advisor dc:contributor.advisor

• Jefferson W. Tester.

• Chemical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/43203

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/43203