Alcohol to Bromide/Chloride/Iodide using Appel reaction

General Procedure-1 (for Chloro and Bromo):

Alcohol (1 eq) and triphenyl phosphine (2 eq.) are taken in dichloromethane (10 Vol) and  cooled to 0 ^oC. CBr₄ or CCl₄ (2 eq.) in dichloromethane (10 Vol) is added dropwise and the mixture stirred at room temperature. The reaction is monitored by TLC. The reaction mixture is filtered to remove the by-product triphenylphosphine oxide. The filtrate (i.e. organic layer) is successively washed with water (15 ml x 2) and brine solution (15 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude product is purified by column chromatography.

General Procedure-2 (for Iodo):

Alcohol (1 eq) and triphenyl phosphine (2 eq.) are taken in DCM (10 Vol) and  cooled to 0 ^oC. Iodine (2 eq) and Imidazole (3 eq.) in dichloromethane (10 Vol) is added dropwise at 0 ^oC and the mixture stirred at room temperature. The reaction is monitored by TLC. The reaction mixture is filtered to remove the by-product triphenylphosphine oxide. The filtrate (i.e. organic layer) is successively washed with saturated solution of sodium thiosulphate (10 Vol), water (10 Vol x 2) and brine solution (15 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude product is purified by column chromatography.

Note:

• The most preferable solvent is DCM and THF. The reaction is usually performed at RT

• The by-product namely triphenylphosphine oxide (TPPO) is usually removed by filtration

For more details on reactions and reagents, 
refer to the tab "Reaction, Reagents and Mechanism"

Typical Procedure:

• Bromination of Diethylene Glycol (ChemSpider) — Open access

• Bromination of an alcohol (ChemSpider) — Open access

• Appel-reagent-mediated transformation of glycosyl hemiacetal derivatives into thioglycosides and glycosyl thiols. Beilstein J. Org. Chem. 2013, 9, 974–982 — Open access

• Bromination of an Alkyl Alcohol through the Appel Reaction (TCI) — Open access

• Iodination of BOC protected phenylglycinol (ChemSpider) — Open access

• Substitution of hydroxy by iodide in phthalic anhydride protected phenylglycinol (ChemSpider) — Open access

• Alcohol to Iodide-1 (OrgSyn) — Open access

For more details on large-scale reactions and OPRD procedures, 
refer to the tab "Scale-up & Green Chem"

WO2010045258, page No. 256

Appel reaction has its own restrictions, as both CCl₄ and CBr₄ are not environment-friendly. However, environmentally benign reagents are being considered in this context

Environmentally benign Appel reaction:

• An environmentally benign and high-rate Appel type reaction, React. Chem. Eng., 2022, 7, 1650-1659 — Open access

– Dimethyl hydantoin derivatives such as DBH, DCH, DIH have been used as benign reagents

Green Chemistry Aspects:

• Development of a More Sustainable Appel Reaction, ACS Sustainable Chem. Eng. 2020, 8, 5, 2300–2309