Solvent- and Catalyst-free, Quantitative Protection of Hydroxyl, Thiol, Carboxylic Acid, Amide and Heterocyclic Amino Functional Groups

Undergraduate #30
Discipline: Chemistry and Chemical Sciences
Subcategory: Chemistry (not Biochemistry)

Mia Jawor - Western Michigan University
Co-Author(s): Basil M. Ahmed and Gellert Mezei, Western Michigan University, Kalamazoo, MI

A truly green, solventless and catalyst-free method has been developed for the quantitative protection of various functional groups using 3,4-dihydro-2H-pyran (DHP) under its own pressure at 125°C. Advantages of this new technique are numerous: (a) no work-up or laborious puriﬁcation steps are required; (b) no additional chemicals are employed; (c) no waste products are generated; (d) the protected intermediate can be used in the next synthesis step in the same ﬂask in which the protection was carried out; (e) as there are no losses during the protection step, the overall yield is maximized; (f) the robust tetrahydropyranyl protecting group allows substrate derivatization under a variety of reaction conditions, yet can conveniently be removed by mild acidic hydrolysis. The inﬂuence of substrate acidity, miscibility of substrate and DHP, amount of DHP employed, nucleophilicity of the atom to be protected, steric hindrance, reaction time and reaction temperature on the eﬃciency of the protection reaction is discussed.

Funder Acknowledgement(s): This material is based upon work supported by the National Science Foundation under Grant No. CHE-1404730.

Faculty Advisor: Gellert Mezei, gellert.mezei@wmich.edu

Role: I did the majority of the reactions in the pressure tube at various temperatures. In the beginning of the project, I used ampoules and various sizes of pressure tubes before finding the right size pressure tube. I took the hydrogen and carbon nuclear magnetic resonances (1H and 13C NMRs).