Carboxylic acids, amides prepared bromination

Several trivial but highly useful reactions are known to convert one acceptor-substituted allene into another. For example, the transformation of allenic carboxylic acids is possible both via the corresponding 2,3-allenoyl chlorides or directly to 2,3-allen-amides [182,185], Allenylimines were prepared by condensation of allenyl aldehydes with primary amines [199]. However, the analogous reaction of allenyl ketones fails because in this case the nucleophilic addition to the central carbon atom of the allenic unit predominates (cf. Section 7.3.1). Allenyl sulfoxides can be oxidized by m-CPBA to give nearly quantitatively the corresponding allenyl sulfones [200]. The reaction of the ketone 144 with bromine yields first a 2 1 mixture of the addition product 145 and the allene 146, respectively (Scheme 7.24). By use of triethylamine, the unitary product 146 is obtained [59]. The allenylphosphane oxides and allene-... 

Bromination of ketone 3.17 gives 3.18 which can be converted to azide 3.19. Hydrogenation of 3.19 in the presence of hydrochloric acid affords aminoketone hydrochloride salt 3.20. Such aminoketones are often isolated as the corresponding salts because the free aminoketones are prone to dimerisation, having both nucleophilic and electrophilic centres. (For a common alternative preparation of aminoketones, see the Knorr pyrrole synthesis, Chapter 2.) Liberation of the free base of 3.20 in the presence of the acid chloride affords amide 3.21 which is cyclised to oxazole 3.22. Ester hydrolysis then affords the biologically-active carboxylic acid 3.23. 

In the second route to l,20 acid chloride 23, prepared by treatment of 5-chlorothiophene-2-carboxylic acid 28 with SOCl2 is coupled with (5)-3-amino-1,2-propanediol hydrochloride 29 in the presence of NaHCCh to furnish the dihydroxy amide 30 (Scheme 3). The primary alcohol in 30 is then brominated by a solution of HBr in HOAc to produce the bromohydrin 31, which is then condensed with the morpholinoaniline derivative 18 to yield 32. Finally, the ring closure with N,N -carbonyldiimidazole (CDI) afforded 1. 

Related anchored l,l,3,3-tetraphenyl-2-oxa-l,3-diphospholanium bis-triflate (39) has been prepared by reaction of brominated poly(styrene-co-divinylbenzene) resin 38 with the phosphorous anion generated from l,2-bis(diphenylphosphino)ethane and sodium naphthalenide followed by further oxidation and reaction with triflic anhydride (Scheme 7.13) [55]. This supported reagent has also been employed, to a lesser extent than 37, for the formation of esters and amides by reaction of carboxylic acids with primary alcohols and amines, respectively. 

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