Visible light induced electron transfer processes in amine deprotection reactions

Date of Completion

January 2000

Keywords

Chemistry, Organic|Chemistry, Physical

Degree

Ph.D.

Abstract

During a multistep synthesis, protecting groups are often employed for the amino group to reduce its basicity and nucleophilicity. The benzyl group is a common protecting group for amines. However, its deprotection involves harsh chemical conditions. ^ The purpose of this research is (1) seek a mild debenzylation method by a visible light induced electron transfer reaction, and (2) develop a novel visible light removable quinoline type protecting group for amines which offers some advantages over the benzyl group. ^ Photochemical debenzylation of benzylated tertiary amines was carried out using an inexpensive spotlight, a dye as a photosensitizer and acetonitrile-water as solvent. Illumination under nitrogen led to the cleanest reaction, though under oxygen the reaction was faster. The reaction was about ten times faster in the presence of a cupric salt. The presumed mechanism of reaction involves a photoinduced electron transfer, and a coordination involving cupric ion seems to improve the quantum efficiency of this process. This reaction has been studied on a family of compounds, on quantities of amine as large as 10 grams. This deprotection method was compatible with a wider range of functionality than strong reductive methods for benzyl cleavage. ^ Benzyl protected secondary amines reacted slowly under the same condition but could be transformed into imines on irradiation in acetonitrile and methanol (1:1) solutions. Mild acid hydrolysis led to the desired deprotection, liberating the primary amine as the product. Varying photosensitizers, solvent and salt effects were studied. Inorganic salt, such as magnesium perchlorate increased the rate of the reaction three-fold. The deprotection reaction was compatible with organic compounds bearing other functional groups, such as hydroxyl groups, amides, esters, ketones and double bonds. ^ In order to develop an improved type of benzyl protecting group, a phenyl quinoline system as a possible photoremovable protecting group for amines was explored. The most effective compound was 2-p-tolyl-6-methoxy-4-quinolinemethyl group, and the structure-activity relationships were explored. Primary and secondary amines reacted with the necessary precursor to give amines which were photochemically cleaved in rapid process in good yield, making this moiety a candidate in photoremovable protecting group. Several compounds were successfully protected and deprotected in this manner. ^

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