Bromine, reaction with amides

Bromination of the methyl group of (249) with A -bromosuccinimide, followed by reaction with excess secondary amine gave (250) which shows combined analgesic and antitussive properties. The Reformatsky reaction has also been used for the preparation of 2-amino-ethyl 3,3-diaryl-3-hydroxypropanates (251) as well as their dehydration products. The propene amides (252) have also been prepared for pharmacological evaluation. In l-methyl-3-bis (2-thienyl)-... 

Allylmagnesium bromide, 41, 49 reaction with acrolein, 41, 49 5-Allyl-l,2,3,4,5-pentachlorocyclopen-tadiene, 43, 92 Allyltriphenyltin, 41, 31 reaction with phenyllithium, 41, 30 Aluminum chloride, as catalyst, for isomerization, 42, 9 for nuclear bromination and chlorination of aromatic aldehydes and ketones, 40, 9 as Friedel-Crafts catalyst, 41, 1 Amidation, of aniline with maleic anhydride, 41, 93... 

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). 

Benzotriazol-l-yl)methyl]triphenylphosphonium chloride 848 reacts with BunLi and aldehydes to give l-(alken-l-yl)benzotriazoles 849. Addition of bromine to the double bond of derivatives 849 followed by a reaction with amines furnishes amides 850. A variety of primary or secondary amines can be used. This way aldehydes are conveniently homologated and converted to amides with a one-atom longer chain (Scheme 136) <2004ARK(ix)44. 

On the other hand, nitrosyl bromide is ineffective. This may be attributed to the fact that the reagent is extensively dissociated to afford nitric oxide and molecular bromine. Furthermore, in the case of some amides, reaction with nitrosyl bromide results in the formation of complex crystalline compounds containing reactive bromine. 

Boron trifluoride and boron trifluoride-diethyl ether complex can be used as a source of fluoride ions in the presence of hypobromites and hypochlorites, e.g. methyl hypobromitc, tert-butyl hypobromite, methyl hypochlorite in carbon tetrachloride at 25 C. The addition of bromine monofluoride" and chlorine monofluoride" to various alkenes is accompanied by the formation of the corresponding alkoxybromides and alkoxychlorides which hinder the isolation of the halofluorinated products.57 jV-Bromo- and A -chloro-substiluted alkyl- and arylamines. -amides, and -imides, A -chloro-A,-methylamine, A -bromo-A -methylamine, A -chloro-A, /V-dimethylamine, A-bromo-A.A-dimethylamine, ACV-dichloro-A -methylamine, V,fV-dibromo-,V-mcthylaminc, A -bromosuccinimide, -V-chlorosuccinimide, Af-bromoacct-amide, A.A -dichlorourethane, can be used in the reaction instead of the hypohalites. The reactions with various alkenes conducted in dichloromethane at room temperature in the presence of boron trifluoride-diethyl ether complex produce bromofluoro and chlorofluoro addition products in 40-80 % yield. However, the reactions are complicated by the addition of A -halo-succinimides and Af.A-dichlorourcthane to the C = C bonds.58... 

Aldehydes are still used to prepare diuretics (82USP4338435) and antihypertensives (87USP4634689), e.g., when 106 is heated with 6-bromohexanal, thiadiazine 107 (X = Br) results. Substituted sulfonamide 106 can apparently be made from the corresponding disulfonyl chloride by sequential amidation with methylamine and then benzylamine. The presence of the bromine moiety in 107 allows 107 [X = PO-(OH)CH2COOH] to be made by reaction with diethyl carboethoxy-methylphosphonite [(EtO)2PCH2COOEt] and subsequent saponification of the phosphinate and acetate groups. Hence, condensation in trifluo-... 

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