A-haloamide

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-... 

Preparation from Nitrene Intermediates. A convenient, small-scale method for the conversion of carboxyhc acid derivatives into isocyanates involves electron sextet rearrangements, such as the ones described by Hofmann and Curtius (12). For example, treatment of ben2amide [55-21-0] with halogens leads to an A/-haloamide (2) which, in the presence of base, forms a nitrene intermediate (3). The nitrene intermediate undergoes rapid rearrangement to yield an isocyanate. Ureas can also be formed in the process if water is present (18,19). 

There are related procedures involving A -haloamides which lead to lactones via iminolactone intermediates ... 

A iD-Corticoids have been important intermediates since it was shown ° that substitution at C-9 enhances anti-inflammatory activity. These olefins are usually obtained from 11a- or 11)5-alcohols, and consequently several refined methods have been devised for effecting this dehydration. It is desirable that such methods be compatible with the presence of A" -3-ketone and 17-hydroxy functions. The first direct procedure for which high yields were claimed was described in a patent issued to Upjohn. According to this method, the alcohol (11a or )5) is treated first with A-bromoacetamide in pyridine, then with sulfur dioxide. Recently it has been claimed " that the A-haloamide/sulfur dioxide method gives results superior to other methods, although the methanesulfonyl chloride/sulfur dioxide procedure (see below) apparently was not compared (see also ref. 94). 

Enol ethers are readily attacked in buffered medium by electrophilic reagents such as halogens, A -haloamides, perchloryl fluoride and organic peracids to give a-substituted ketones. Similarly, electrophilic attack on... 

Tetramethylguanidinium azide, an azide salt that is readily soluble in halogenated solvents, is a useful source of azide ions in the preparation of azides from reactive halides such as a-haloketones, a-haloamides, and glycosyl halides.74... 

This chapter will address the synthesis, theoretical and physical properties and reactivity of a number of different classes of anomeric hydroxamic esters. Principal categories include A-aUtoxy-A-haloamides (XNO systems), A-acyloxy-A-alkoxyamides and A,A-dialkoxyamides (ONO systems), A-alkoxy-Al-aminoamides (ONN systems) and N-... 

Anchimeric assistance by the aUcoxyl oxygen lone pair promotes heterolytic S v 1 and reactions at nitrogen as well as homolysis of the N—Cl bond. A-Haloamides are also amidyl radical sources" but their heterolytic reactivity is known to involve positive, rather than negative, halogen ... 

The stoichiometric equivalents of halogen fluorides, i.e. chlorine monofluoride, bromine monofluoride and iodine monofluoride, have found a wide application in addition reactions to double bonds. The equivalents are obtained by reacting A -haloamides or free halogens in combination with hydrogen fluoride or its salts as the source of fluoride ions. The reactions proceed under mild conditions at — 80 to 20 "C in anhydrous hydrofluoric acid or diethyl ether, tetrahydro-furan, dichloromethane or chloroform mainly by electrophilic addition with Markovnikov-type regioselectivity (anti addition).26-28... 

This new rearrangement is applicable in general to a-bromo-, x-chloro-, and a,a-dihrotnoketone enolates. It is formally isoelectronic with the Hofmann rearrangement of a-haloamides.5... 

Photoannelation of glycals by nitrenes affords the 1-2 aziridine intermediates which are transformed into aminosides 43 in the presence of alcohols [43]. A similar approach with a photochemical cc-addition of A-haloamides to glycals is also possible to yield mainly 1-2 trans aminosides (Scheme 20) [44 a], This similar preferential tx-addition is in contrast with the reported p-addition on the P-face of the thioacetyl radicals [44 b],... 

Scheme 6.10 Catalytic asymmetric Darzens reaction of a-haloamides.

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 intermolecular Sml2 Reformatsky reactions of a-haloamides have similarly received little attention however, Ohta showed that 7V,tV-dibenzyl-a-haloamides undergo efficient coupling with a range of aldehydes and ketones (Scheme 5.94).148... 

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 . 

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