טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentToledo Hila
SubjectOrganocatalytic Oxidation of Aldehydes to Esters and Amide
DepartmentDepartment of Chemistry
Supervisor Professor Alex.m Szpilman
Full Thesis textFull thesis text - English Version


Abstract

Acylations are ubiquitous fundamental processes of importance in both academia and industry. Indeed, a recent survey has shown that acylations of amines or alcohols is one of the most common reactions performed in pharmaceutical companies1-4. Due to the significant and essential role acylations in organic chemistry, the demand for efficient process increased.

Surveying the literature, showed that catalytic oxidation of primary alcohols into esters or amides is rare. Generally, the classical methods involve the oxidation of an alcohol to an aldehyde, oxidation of the aldehyde to the carboxylic acid, and its subsequent conversion into an activated species either in a separate step or in situ during acylation. Combination of two or more of these steps into single operation with available and inexpensive reagents would increase efficiency and reduce the generated waste. 

Our group has developed a direct oxidative TEMPO catalyzed dimerization of primary alcohols to form ester in good yields5. However, catalytic oxidation of primary alcohols to unsymmetrical esters and amides was found to be very challenging. Each attempt afforded the desired product but also the symmetric ester and aldehyde. Thus, this project focuses on developing efficient acylation from the intermediate product, aldehyde.

We found that TEMPO catalyzed efficiently oxidation of aldehyde to mixed anhydride with pivalic acid6 (2). The mixed anhydrides may be converted in-situ into a wealth of esters and amides in yields of 55-97% .