Bromine with amides

Poly(phenylene oxide)s undergo many substitution reactions (25). Reactions involving the aromatic rings and the methyl groups of DMPPO include bromination (26), displacement of the resultant bromine with phosphoms or amines (27), lithiation (28), and maleic anhydride grafting (29). Additional reactions at the open 3-position on the ring include nitration, alkylation (30), and amidation with isocyanates (31). 

The N-bromination of amides with bromine and alkali has been extensively researched as the first step of the Hofmann degradation. However, it is difficult to isolate the N-bromoamides because of their subsequent reaction to produce amines, which proceeds very readily under excessive alkaline conditions. Now, the reaction of amides with a stoichiometric amount of BTMA Br3 and sodium hydroxide in ice-water gave N-bromoamides in fairly good yields. Our method can be applied to various types of aliphatic, aromatic, and heterocyclic amides (Fig. 31) (ref. 39). 

Fig. 31. N-Bromination of amides with BTMA Br3 Hofmann degradation of amides...

The compounds 12,14 and 15 can be prepared from parent lysergic acid amides by bromination with NBS or PHT, but not the compounds of the type 12. The latter structure is very sensitive and under these circumstances only degradation products were obtained. Besides it was necessary to use much milder reagent, e.g. bromine bonded onto polymeric matrix with polyvinylpyrrolidone or polyvinylpyridine structure (29) ... 

Hetero substitutents exchange readily, though it has been shown that substitution of bromine by amide ion occurs through the Sn (ANRORC) mechanism. Replacement of an amino group with ammonia or hydrazine occurs by both and Sn (ANRORC) mechanisms (84MI5). The only example of this type of nucleophilic substitution in the current literature is the displacement of halogens in tetrazine 288 by alkoxide 289 to yield 290 (85TL4355). 

N-Bromination. Amides are brominated with AcOBr in CCU at room temperature. 

The same method was also used for the synthesis of the anti-malarial compound mefloquine. Heterocyclization of 2-trifluoromethylaniline with trifluoroacetic acid ethyl ester provides 2,8-6w-(trifluoromethyl)-4-hydroxyquinoline. Bromination with phosphorous tribromide, followed a carbon monoxide introduction, affords 2,7-trifluoromethyl-4-carboxylic acid quinoline. Amide formation and pyridine reduction completes the synthesis providing mefloquine in high yields. ... 

Xia et al. [63] developed new acyl AAS having the general structure a-amino-(Ai-acyl)-P-alkoxypropionate. The structure-function relationship of the anionic amino-alkoxypropionates was evaluated, with an emphasis on their antimicrobial properties. The anionic amino-alkoxypropionate was synthesized, starting from propionic acid methyl ester, through alkoxylation with fatty alcohol, bromination, saponification, amidation, acylation with R OCl (acyl chloride), and saponification to obtain the final product. For the detailed procedure, see Xia et al. [63]. 

Formation of 2-Trimethylsilylaziridines. The photochemical or thermal reaction of vinyltrimethylsilane with ethyl azido-formate or phenyl azide provides the trimethylsilylaziridine in modest yields (eq 22). Reduction of the formyl amide gives the parent trimethylsilylaziridine (eq 23). Trimethylsilylaziridines were also formed from the reaction of a-lithiochloromethyltri-methylsilane with imines, but this reaction only works with the imines of aldehydes. The reaction of bromotriazide, formed in situ from the reaction of bromine with sodium azide, with vinyl-silanes forms silylaziridines as well. This reaction was not carried out with vinyltrimethylsilane. However, vinyltriphenylsilane gave a 50% yield of 2-triphenylsilylaziridine under these conditions. 

The starting material is a vinylamide, and it needs to be iodinated or brominated with retention of the amide Need to make a halogenated vinyl ketone bearing an electron-deficient arene... 

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