Sustainable strategies for alcohol halogenation

Alkyl halides appear widely in the structures of medicinal compounds and as key synthetic precursors in the pharmaceutical industry. Bimolecular nucleophilic substitution reactions of alcohols are commonly employed in the formation of new carbon–halogen bonds. However, achieving substitution at the carbon next to an alcohol often comes at the cost of atom economy. This work is centred on enhancing the efficiency of alcohol activation towards halogenation, with respect to halide waste generation. Though many organocatalytic routes to alcohol halogenation have been developed, these methods often require the use of polyhalogenated starting materials, generating a super-stoichiometric amount of halogenated waste. Reported herein is a novel strategy for alcohol activation mediated by diphenyl H-phosphonate, capable of furnishing a wide variety of alkyl iodides and benzyl chlorides. In both instances, each process employs the lowest theoretical loading of the halogenating agent (e.g. 0.5 equivalent of I2 or 1 equivalent of NaCl), avoiding halide waste production. In the case of benzyl chloride synthesis, common table salt was proven to be an effective stoichiometric source of nucleophilic chloride. This offers an innocuous, low-cost alternative to more common chlorinating agents (e.g., SOCl2, PCl5, (COCl)2), which can often prove hazardous to handle. Furthermore, the diphenyl H-phosphonate promoter can be generated via a PCl3-free route, further minimizing the halogenated waste associated with the overall process. This is an operationally convenient strategy, employing commercially available reagents in a “one-pot/dump and stir” reaction. The true sustainable nature of the methodology has also been explored, particularly with respect to alcohol iodination, where solvent-free conditions have been applied and process green metrics evaluated. This developed methodology offers a practical and competitive route to alcohol iodination/chlorination, characterised by reduced halide waste production and enhanced sustainability.

Grantor dc:publisher

University College Cork

Year dc:date.issued

2026

Author dc:creator

• Furlong, Emma

Advisor dc:contributor.advisor

• Mcglacken, Gerard P.

• Alkyl halide
• Halogenation
• Green chemistry
• Alkyl iodide
• Alkyl chloride
• Alcohol halogenation
• Low waste

Statement dc:rights

• © 2026, Emma Furlong.

Licence dc:rights.uri

• https://creativecommons.org/licenses/by-nc-nd/4.0/

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10468/18889

OAI identifier oai:identifier

oai:cora.ucc.ie:10468/18889