Microwave-assisted benzyl mono- and dibromination in diethyl carbonate as environmentally friendly alternative to radical bromination in carbon tetrachloride

Chlorinated Solvents: Their Advantages, Disadvantages, and Alternatives in Organic and Medicinal Chemistry

“…Throughout the literature available on radical benzylic bromination reactions employing NBS, a number have been successfully carried out using cyclohexane as solvent. − Other methods such as “on water” benzylic bromination, the use of MeOAc as solvent, and microwave assisted benzylic bromination in EtOAc and diethyl carbonate have also been demonstrated as successful approaches, as have solvent-free methods . Benzylic bromination may be achieved alternatively using tribromoisocyanuric acid in EtOAC without the need for catalysts or initiators, a considerably safer process .…”

Synthesis and Structure–Activity Relationships for Extended Side Chain Analogues of the Antitubercular Drug (6S)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824)

“…In the latter case ( 63 ), protection of the sulfonamide NH (as its Boc derivative) was necessary in order to obtain a sufficient yield in the final alkylation step with 95 (19% after removal of the Boc group with TFA in CH 2 Cl 2 ). Reversed amide and sulfonamide congeners ( 64 and 65 ) were alternatively acquired from the novel phthalimide derivative 144 (Scheme A), which was made by alkylation of alcohol 95 with the known bromide 143 . Here, deprotection of 144 using hydrazine hydrate gave the unstable aniline 145 , which successfully underwent sulfonylation and acylation reactions with the commercial chlorides to provide the final products in reasonable overall yield (40–48%).…”

Synthesis of lamellarin alkaloids using orthoester-masked α-keto acids

“…Initial work investigated the desired functionalisation of methyl-OBO-ketone 1 with aryl bromide 19 and α-bromo benzyl nitrile 20 . Protection of 4-hydroxybenzyl nitrile ( 21 ) with 2-bromopropane gave 22 and benzylic bromination using NBS/dibenzoyl peroxide in diethyl carbonate21 gave 20 . Using the previously developed conditions,11 NaO t Bu and Pd(dtpbf)Cl 2 (5 mol%) in THF, methyl-OBO-ketone 1 coupled with aryl bromide 19 .…”