A simple yet novel strategies for the synthesis of pharmacologically versatile benzoxazole and benzothiazole scaffolds via transamidation.
Loading...
Date
2022
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Transamidation is a popular way for amide transformation from another amide despite conventional
amide bond formation methods. Acid and acid chloride were utilised as starting ingredients in previous
procedures. Transamidation has shifted the perspective of researchers on amide synthesis. Nowadays,
many methodologies have recently come to light for amide transformation, using non-metal and metalmediated
techniques. On the other hand, a few approaches involving amide bond activators have been
reported. Moreover, N-Boc, Tosyl, and Mesyl groups are commonly utilised as amide bond activators.
As a result, many amides transformations have been synthesised and published in the literature over the
last few decades. Based on previous research, we have attempted to develop cost-effective and novel
techniques of transamidation for unactivated amides, which could serve as a potential alternative to
synthesising amide bond containing compounds from lab to plant scale. We also demonstrated a novel
approach for synthesising 2-substituted benzoxazole/benzothiazole compounds using this
transformation.
The history and development of unactivated amides transformation are briefly described in Chapter 2.
This chapter also discusses different transamidation methods for primary, secondary, and tertiary
unactivated amides that are transformed into other amides without the need for an amide bond activator.
The development of a novel green, efficient catalyst-free, one-pot synthetic methodology to synthesise
amides is described in Chapter 3. Under the optimisation investigations, the effects of various acids,
solvents, temperatures, and time intervals were also described. The reaction was catalysed by
hydrochloride, which activated the carbonyl bond, and then attacked the carbonyl carbon with an
additive amine as a nucleophile. Finally, the amine as a byproduct is removed, resulting in the desired
converted amide. Furthermore, this new transamidation process allows for a wide range of amide types,
including primary, secondary, and tertiary. This approach also works with a variety of primary and
secondary amines, including aliphatic and bulky, hetero-aromatic substituted amines.
To continue the work begun in Chapter 4, we develop a new solvent-free and metal-free method for
synthesising 2-substituted benzoxazole and benzothiazole in Chapter 4. In this approach, we increase
the temperature and employ substituted 2-aminophenols or 2-aminothiophenols instead of amines. To
lead the annulation product, the oxygen or sulphur atom of phenol or thiophenol attacks the carbonyl
carbon of the transformed amide group. Furthermore, this technique works well with a variety of
substituted 2-aminophenols. Additionally, the amide scope for this reaction is quite broad.
Chapter 5 describes the development of a new method for the transamidation of aliphatic amides using
CuCl2 as a catalyst. The effects of various catalysts and Lewis acids and the effect of different solvents
were explained. Moreover, the annulated substituted 2-benzoxazole and 2-benzothiazole derivatives
obtain in the case of 2-aminophenol and 2-aminothiophenol. Besides, this new versatile methodology
provides a wide substrate scope for the synthesis of different functionally substituted amides and 1,3-
benzoxazole scaffolds. It can be further exploited as building blocks for the synthesis of pharmaceutical
drugs.
Description
Doctoral Degree. University of KwaZulu-Natal, Durban.