Amides Haloamides

The general theory behind the process is that the hypohalite will convert the amide to a haloamide. This then spontaneously changes to the isocyanate when heated and decomposes to the amine from the water present. In effect, all that happens is that a Carbonyl (CO) group is stripped off the starting amide to yield the corresponding amine. Yields pre- purification are around 80%, post-purification average around 65%. Certain uses of the result-... 

In this paper Speziale and Smith 109) described experiments which led them to modify the mechanism proposed earlier 108) for the reaction of trivalent phosphorus compounds with haloamides. The first step is considered to be attack of the trivalent phosphorus compound on a chlorine atom of the halo amide (132) to produce a resonance-stabilized enolate ion (133). This is reasonable since under conditions where the trichloroamide... 

Currently the most popular of the pseudohalides are N-haloamides. These reagents are used in conjunction with the solvent or an added nucleophilic reagent to give overall 1,2-addition of a halogen and a nucleophile to the alkenic substrate. The amides of choice seem to be N-halosuccinimides. The low nu-cleophilicity of the succinimdyl anion allows for a variety of nucleophiles to attack the initially formed halonium ion. 

A general process for haloamidation of alkenes has been developed, which is characterized by the addition of a bromine atom and an amide nitrogen in an anti sense to the olefinic double bond [(7) - (8)]. The process involves the use of an A-bromoamide and a Lewis acid as a source of Br+, which reacts with the alkene. The amide group is derived from a nitrile and a water molecule, which serve as nucleophiles for the overall three-component reaction. The reaction has been shown to be general for a broad range of alkenes and nitriles an analogous chloroamidation reaction has also been demonstrated 25... 

A-Haloamides and imides are a most versatile group of halogenating reagents. They are normally prepared in an aqueous solution by reaction of the parent amide/imide with the corresponding hypohalite. An improved method for the synthesis of A-bromo amides/imides has recently been published, in which the parent compounds are oxy-brominated in aqueous solution by a mixture of HBr/NaBr03 or NaBr/NaBr03/H2S04 (equation 95)700. 

The nitrogen source for the aziridination of alkenes, a nitrene or nitrenoid, can be generated in various ways (1) oxidation of a primary amine (2) base-induced -elimination of HX from an amine or amide with an electronegative atom X (X = halogen, O) attached to the NH group or by -elimination of metal halides from metal A-arenesulfonyl-A-haloamides (3) metal-catalyzed reaction of [A-(alkane/arenesulfonyl)imino]aryliodanes (4) thermolytic or photolytic decomposition of organyl azides and (5) thermally induced cycloreversion reactions . 

A -Haloamides also undergo the Hofmann rearrangement This reaction provides a useful method of making amines from amides with the loss of the carboxyl carbon atom. 

Step (1) is the halogenation of an amide. This is a known reaction, an N-haloamide being isolated if no base is present. Furthermore, if the N-haloamide isolated in this way is then treated with base, it is converted into the amine. 

Isocyanates derived from the higher aliphatic amides react more rapidly with the haloamide salts than with water and alkali, so that, when these amides are subjected to the Hofmann reaction in aqueous mediiun, only small amounts of the expected amines are formed. Although amines arise from the hydrolysis of the alkyl acyl ureas, they are largely oxidized to nitriles by the excess of hypobromite present. 

Carbonylation Reactions. A three-component palladium-catalyzed amidocarbonylation reaction provides IV-acylamino acids from aromatic and aliphatic aldehydes or acetals with amides under elevated CO pressure (60 bar) in the presence of PdBr2, PPhs, LiBr, an acid additive (typically H2SO4), and iV-methyl-2-pyrrolidone. Mechanistically, the palladium-catalyzed amidocarbonylation reaction is proposed to proceed through the in situ formation of an a-haloamide and Pd(0) species, which can undergo oxidative addition, followed by CO insertion, and lastly hydrolysis of the acyl palladium complex to afford the product and regenerate the catalyst (eq 45). 

Since a-haloesters undergo the Reformatskii reaction, a-haloamides may also be subjected to this reaction to give amides. 

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