Synthetic Approaches to Acyl Hydrazides and Their Use as Synthons in Organic Synthesis

Abstract

Acyl hydrazides constitute very important moieties in organic chemistry and have been employed as starting materials for different transformations to many classes of organic compounds. In this review, at first the approaches towards the synthesis of acyl hydrazides are presented. Furthermore, in the second part, the uses of this skeleton as an important intermediate for the synthesis of useful organic compounds are analyzed.1 Introduction2 Approaches towards the Synthesis of Acyl Hydrazides2.1 Synthesis of Acyl Hydrazides from Aldehydes2.2 Synthesis of Acyl Hydrazides from Carboxylic Acid Derivatives3 Acyl Hydrazides as Useful Synthons in Synthetic Organic Transfor mations­3.1 Acyl Hydrazides as Synthetic Precursors for the Synthesis of Car bonyl Compounds3.2 Acyl Hydrazides as Synthetic Precursors for the Synthesis of Het erocyclic Rings4 Conclusion

Light-accelerated “on-water” hydroacylation of dialkyl azodicarboxylates

“…Bringing together the literature knowledge and our studies, we can conclude by proposing the following mechanism (Scheme 6). In the literature, the mechanism for the hydroacylation of dialkyl azodicarboxylates is mostly proposed involving radical intermediates, 2 although some ionic paths have also been reported. 2 In the literature, air and/or water are well-accepted in being able to generate acyl radical I from aldehydes 1 , a process which is highly dependent on air, but water is known and proposed to accelerate this process (Scheme 6A, Pathway II).…”

“…In the literature, the mechanism for the hydroacylation of dialkyl azodicarboxylates is mostly proposed involving radical intermediates, 2 although some ionic paths have also been reported. 2 In the literature, air and/or water are well-accepted in being able to generate acyl radical I from aldehydes 1 , a process which is highly dependent on air, but water is known and proposed to accelerate this process (Scheme 6A, Pathway II). 16,17,29 b ,30 a – c ,34 b It is also well accepted that acyl radical I can react with different electrophiles, like DIAD, leading to the desired products (Scheme 6C).…”

“…1 There are numerous ways one could envisage the retrosynthetic analysis to forge a new C–N bond; however, a reaction that is not so often discussed, but in the last few years has received a lot of attention, is the use of dialkyl azodicarboxylates and aldehydes for the formation of acyl hydrazides. 2 The unambiguous and environmentally friendly formation of acyl hydrazides is of great importance due to the wide range of products that may be obtained from them, such as the drugs Vorinostat and Moclobemide. 3 At the same time, the starting materials of this reaction are aldehydes, which are feedstock reagents with applications in medicinal chemistry and agrochemistry, 4 and dialkyl azodicarboxylates.…”

“…Historically, the first reported approach, as well as most of the synthetic strategies in the literature, for the construction of acyl hydrazides involves the use of transition metals as catalysts (Scheme 1A). 2 Among the metals employed, rhodium acetate, 8 zinc acetate, 9 copper acetate, 10 copper oxide nanoparticles 11 or magnetite impregnated with cobalt 12 have been described as the catalyst of choice depending on the reaction conditions (Scheme 1A). In 2014, Xu and coworkers described the synergistic effect of a Lewis acid (CoCO 3 ) with a Brønsted acid, namely TFA, for the promotion of the reaction between aromatic or alkyl aldehydes and dialkyl azodicarboxylates (Scheme 1B).…”

Synthesis of Acid Hydrazides from Carboxylic Acids in Continuous Flow

“…Acid hydrazides are a versatile class of organic compounds, which serve as fundamental building blocks in a number of pharmaceutical, agrochemical, and materials science applications (Scheme A). − In addition, they function as valuable chemical intermediates in the synthesis of ketones, hydrazones, amides, and heterocyclic rings . As a subset of this family, acid dihydrazides find significant applications in a variety of industrial and academic settings owing to their benchtop stability and unique reactivity profile .…”