A novel simple and efficient bromination protocol for activated arenes

Synthetic Route Discovery and Introductory Optimization of a Novel Process to Idebenone

“…Several more examples are given in our previous disclosure. 26 With the low cost and environmentally friendly process for the production of the aromatic bromide 2 available, the next step ought to be a coupling reaction. The Heck coupling involving the bromobenzene 2 and the commercially available dec-9-en-1-ol (5), Scheme 3, appeared to be a potential path to produce the complete Carbone skeleton needed for the Idebenone.…”

“…A large number of brominating protocols have previously been disclosed, unfortunately most of them will not fulfill some of our important objectives, namely low environmental impact and easy scalability. In this context, we designed and realized recently a novel bromination protocol where we utilized the two low-cost compounds 1,2,3-trimethoxy-5-methylbenzene ( 1 ) as substrate and potassium bromide as the only bromine source. KBr as bromine source is very attractive since this compound has low toxicity and is easy to handle even at large scale.…”

Acetic Anhydride (Ac2O)

“…1 It is a cheap and commercialized reagent widely used in the synthesis of oxazolones, 2 thiohydantoins, 3 thioacetates, 4 enamides, 5 geminal diacetates, 6 thiadiazoles, 7 as well as in the preparation of carbonyl compounds from imines. 8 Further, it is used in acetylations, 9 brominations, 10 Grignard reactions, 11 and reductive acylations of nitropyrroles. 12 Preparation Ac 2 O (1) was formerly produced starting from sodium acetate and acetyl chloride (A).…”

“…Ac 2O followed by a dropwise addition of nitric acid in Ac 2 O 10. (J) 3,5-Bis(trifluoromethyl)phenylmagnesium chloride reacts with Ac 2 O to produce 3,5-bis(trifluoromethyl)acetophenone.…”

Simple and Efficient Method for the Halogenation of Oxygenated Aromatic Compounds

“…Direct ortho chlorination of phenols is effected using of tert-butyl hypochlorite, 4 N,N-dichlorobutylamine, 5 N-chlorodialkylamines/ silica gel, 6 Cl 2 or sulfuryl chloride catalysed by amines, 7,8 and sulfuryl chloride in the presence of tert-butylaminomethyl polysterene as a heterogeneous amine catalyst. 9 Conventional methods for the synthesis of bromoaromatics involve use of Br 2 /SbF 5 /HF, 10 Br 2 in acetic acid, 11 Br 2 / SO 2 Cl 2 over microporous catalyst, 12 Br 2 /tetrabutylammonium peroxydisulfate, 13 TBHP (70%)/HBr, 14 NBS/ H 2 SO 4 /TFA, 15 NBS/dibromodimethyl hydantoin/ NaOH, 16 NBS/HBF 4 •OEt 2 , 17 NBS/SiO 2 , 18 NBS/over HZSM-5, 19 NBS/TBAB, 20 NBS/SO 3 H-functionalised silica, 21 NBS/ammonium acetate, 22 NBS/PTSA, 23 dioxane dibromide, 24 LiBr/Cu(OAc) 2 /O 2 , 25 3-methylimidazolium tribromide, 26 quinolinium bromochromate in glacial acetic acid, hypobromites, 27 Oxone ® with NaBr 28 or KBr, 29 and KBr/acetic anhydride/HNO 3 .…”