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The haloform reaction from methyl ketones to carboxylic acids is one of the oldest known synthetic organic reactions, which has been used in myriad applications over the decades. The corresponding reaction to produce esters is, however, less developed, as the reaction is generally limited to simple, primary alcohols that are used in solvent‐level quantities, thereby restricting the complexity of esters that can be directly formed. Herein, we detail the development of a general ester‐forming haloform coupling reaction using one equivalent of alcohol. Mechanistic and kinetic modelling studies demonstrated that the key intermediates are formed under equilibrium, which facilitated the development of conditions that are amenable to secondary alcohols. [ABSTRACT FROM AUTHOR]

The haloform reaction from methyl ketones to carboxylic acids is one of the oldest known synthetic organic reactions, which has been used in myriad applications over the decades. The corresponding reaction to produce esters is, however, less developed, as the reaction is generally limited to simple, primary alcohols that are used in solvent‐level quantities, thereby restricting the complexity of esters that can be directly formed. Herein, we detail the development of a general ester‐forming haloform coupling reaction using one equivalent of alcohol. Mechanistic and kinetic modelling studies demonstrated that the key intermediates are formed under equilibrium, which facilitated the development of conditions that are amenable to secondary alcohols. [ABSTRACT FROM AUTHOR]

Heterocyclic chalcones are a recently explored subgroup of chalcones that have sparked interest due to their significant antibacterial and antifungal capabilities. Herein, the structure and solubility of two such compounds, (E)‐1‐(1H‐pyrrol‐2‐yl)‐3‐(thiophen‐2‐yl)prop‐2‐en‐1‐one and (E)‐3‐phenyl‐1‐(1H‐pyrrol‐2‐yl)prop‐2‐en‐1‐one, are assessed. Single crystals of (E)‐1‐(1H‐pyrrol‐2‐yl)‐3‐(thiophen‐2‐yl)prop‐2‐en‐1‐one were grown, allowing structural comparisons between the heterocyclic chalcones and (2E)‐1,3‐diphenylprop‐2‐en‐1‐one, trivially known as trans‐chalcone. The two heterocyclic chalcones were found to be less soluble in all solvents tested and to have higher melting points than trans‐chalcone, probably due to their stronger intermolecular interactions arising from the functionalized rings. Interestingly, however, it was found that the addition of the thiophene ring in (E)‐1‐(1H‐pyrrol‐2‐yl)‐3‐(thiophen‐2‐yl)prop‐2‐en‐1‐one increased both the melting point and solubility of the sample compared with (E)‐3‐phenyl‐1‐(1H‐pyrrol‐2‐yl)prop‐2‐en‐1‐one. This observation may be key for the future crystal engineering of heterocyclic chalcones for pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Discovered in 1822, the haloform reaction is one of the oldest synthetic organic reactions. The haloform reaction enables the synthesis of carboxylic acids, esters or amides from methyl ketones. The reaction proceeds via exhaustive α‐halogenation and then substitution by a nucleophile to liberate a haloform. The methyl group therefore behaves as a masked leaving group. The reaction methodology has undergone several important developments in the last 200 years, transitioning from a diagnostic test of methyl ketones to a synthetically useful tool for accessing complex esters and amides. The success of the general approach has been exhibited through the use of the reaction in the synthesis of many different complex molecules in fields ranging from natural product synthesis, pharmaceuticals, agrochemicals, fragrants and flavourings. The reaction has not been extensively reviewed since 1934. Therefore, herein we provide details of the history and mechanism of the haloform reaction, as well as an overview of the developments in the methodology and a survey of examples, particularly in natural product synthesis, in which the haloform reaction has been used. [ABSTRACT FROM AUTHOR]