Carboxylic acids amide formation from

In his cephalosporin synthesis methyl levulinate was condensed with cysteine in acidic medium to give a bicyclic thiazolidine. One may rationalize the regioselective formation of this bicycle with the assumption that in the acidic reaction mixture the tMoI group is the only nucleophile present, which can add to the ketone. Intramolecular amide formation from the methyl ester and acid-catalyzed dehydration would then lead to the thiazolidine and y-lactam rings. The stereochemistry at the carboxylic acid a-... 

BORIC ACID CATALYZED AMIDE FORMATION FROM CARBOXYLIC ACIDS AND AMINES N-BENZYL-4-PHENYLBUTYRAMIDE... 

Many procedures for the formation of carboxylic acid amides are known in the literature. The most widely practiced method employs carboxylic acid chlorides as the electrophiles which react with the amine in the presence of an acid scavenger. Despite its wide scope, this protocol suffers from several drawbacks. Most notable are the limited stability of many acid chlorides and the need for hazardous reagents for their preparation (thionyl chloride, oxalyl chloride, phosgene etc.) which release corrosive and volatile by-products. Moreover, almost any other functional group in either reaction partner needs to be protected to ensure chemoselective amide formation.2 The procedure outlined above presents a convenient and catalytic alternative to this standard protocol. 

Although there are several reports in the literature on boron-mediated amide formations, the boron reagents had to be used in stoichiometric amounts.1-4-5-6-7-8-9 Recently, Yamamoto et al. presented the first truly catalytic method allowing for a direct amide formation from free carboxylic acids and amines as the reaction partners.10-1112 Best results were obtained by using phenylboronic acids bearing electron withdrawing substituents in the meta- and/or para-positions such as 3,4,5-trifluorophenylboronic acid or 3,5-bis(trifluoromethyl)boronic acid as the catalysts. 

For a review of amide formation from carboxylic acids, see Beckwith, in Zabicky, Ref. 555. pp, 105-109. " See, for example, Bladd-Font Tetrahedron Lett. 1988, 21, 2443. 

Amide formation, from a carboxylic acid and urea, 37, 50 from 2-amino-5-nitroanisole and ethyl benzoylacetate, 37, 4 from aniline and ethyl benzoylacetate, 37, 3... 

NH3 or RNH2 or R2NH Amide formation from carboxylic acid derivatives (mild) or from carboxylic acids (A technical synthesis of nylon-6,6) transamidation [capro-lactame —> nylon-6 (perlon)] Peptide synthesis (Section 6.4.3)... 

Amide formation from carboxylic acids 480 with O-subsituted hydroxylamine hydrochlorides also proceeds in the presence of DCC to give the substituted hydroxamic acid 481 in 91 % yield.451... 

Garcia, J, Uipi, F, Vilarrasa, J, New synthetic tricks. Triphenylphosphine-mediated amide formation from carboxylic acids and azides, Tetrahedron Lett., 25, 4841-4844, 1984. 

Sulfur monochloride Partial formation of acylaminodisulfides from carboxylic acid amides in polar solvents... 

Wallach was the first (1874) to report on the transformation of carboxylic acid amides to amide chlorides by treatment with PCls various types of amides were converted by this reagent to chloromethyleneiminium chlorides (30 equation lg). - > Side reactions can include the a-chlorination of the amide chloride. If excess PCIs is used, the formation of iminium salts with complex ions (31) has been reported. The very labile bromomethyleneiminium bromides (32 equation 19) can be obtained by action of PBrs on tertiary amides. The iodomethyleneiminium salt (33) was prepared from DMF and diphosphorus tetraiodide in CS . ... 

Amide formation from the carboxylic acid is much easier if the acid is first activated. Several activating agents have been developed that greatly facilitate amide formation. Dicyclohexylcarbodiimide (DCC) is used most often (Fig. 17.36). 

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