Carbonylation amides

Perhaps the most extensively studied catalytic reaction in acpreous solutions is the metal-ion catalysed hydrolysis of carboxylate esters, phosphate esters , phosphate diesters, amides and nittiles". Inspired by hydrolytic metalloenzymes, a multitude of different metal-ion complexes have been prepared and analysed with respect to their hydrolytic activity. Unfortunately, the exact mechanism by which these complexes operate is not completely clarified. The most important role of the catalyst is coordination of a hydroxide ion that is acting as a nucleophile. The extent of activation of tire substrate througji coordination to the Lewis-acidic metal centre is still unclear and probably varies from one substrate to another. For monodentate substrates this interaction is not very efficient. Only a few quantitative studies have been published. Chan et al. reported an equilibrium constant for coordination of the amide carbonyl group of... 

Scheme 30) (6). Infrared spectra of the products possess a normal amide carbonyl absorption, indicating that the products are not present on the dipolar form (30) but rather as the neutral A -thiazoline tautomer (31 or 32) (6). 

In addition they may contain ether, amide, carbonyl, sulfone, or other functional groups. References 28 and 29 provide excellent reviews of polyimide chemistry. 

The use of a vinylphosphonium salt as the source of the QQ fragment instead of the more commonly employed 1,2-dicarbonyl substrate is illustrated by the pyrrole synthesis in Scheme 79b (8UOC2570). A particularly interesting feature is the intramolecular Wittig reaction with an amide carbonyl group. A very useful synthesis of pyrroles depends upon the addition of the anion of p-toluenesulfonylmethyl isocyanide (TOSMIC) to a,/3-unsatur-... 

In this series of amides, hydrolysis or aminolysis of a simple ester, cleavage of a silyl groups a cis/trans isomerization, or reduction of a quinone to a hydro-quinone exposes an alcohol that then induces deprotection by intramolecular addition to the amide carbonyl. 

BuLi, THF, -78° O2 or MoOPH, [oxodiperoxymolybdenum-(hexa-methylphosphorictriamide)(pyridine)], 30-68% yield. This method uses the amide carbonyl to direct benzylic metalation. 

Wasserman demonstrated with 0 labeling studies that the amide carbonyl oxygen is incorporated into the oxazole ring upon cyclization... 

The structural feature of ceforanide that is of particular interest is the movement of the C-7 side chain amino moiety from the position a to the amide carbonyl, where it normally resides in ampicillin/cephalexin analogues, to lodgement on a methylene attached to the ortho position on the aromatic ring. 

The interposition of a syn-oximino ether moiety between the amide carbonyl and the aromatic ring has proved richly... 

Following formation of the amide intermediate, a second nucleophilic addition of hydroxide ion to the amide carbonyl group then yields a tetrahedral alkoxide ion, which expels amide ion, NHZ-, as leaving group and gives the car-boxylate ion, thereby driving the reaction toward products. Subsequent acidification in a separate step yields the carboxylic acid. We ll look at this process in more detail in Section 21.7. 

Basic hydrolysis occurs by nucleophilic addition of OH- to the amide carbonyl group, followed by elimination of amide ion (-NH2) and subsequent deprotonation of the initially formed carboxylic acid by amide ion. The steps are reversible, with the equilibrium shifted toward product by the final deprotonation of the carboxylic acid. Basic hydrolysis is substantially more difficult than the analogous acid-catalyzed reaction because amide ion is a very poor leaving group, making the elimination step difficult. 

Conversion of Amides into Amines Reduction Like other carboxylic acid derivatives, amides can be reduced by LiAlH.4. The product of the reduction, however, is an amine rather than an alcohol. The net effect of an amide reduction reaction is thus the conversion of the amide carbonyl group into a methylene group (C=0 —> CTbV This kind of reaction is specific for amides and does not occur with other carboxylic acid derivatives. 

This section also discusses l,5-bcnzodiazepin-2-ones, the corresponding thiones and benzo-diazepinediones. The benzodiazepinones exist in the 1,3-dihydro form 4 A rather than as the 1,5-dihydro tautomers 4B, as shown by 1HNMR spectroscopy.251,252 1Z/-1,5-Benzodiazepine-2,4(3//,5Z/)-diones 5 show NH absorptions at ca. 3180 and 3190, and amide carbonyl bands at ca. 1710 and 1660cm 1.253... 

P-Lactamases are enzymes that hydrolyze the P-lactam ring of P-lactamantibiotics (penicillins, cephalosporins, monobactams and carbapenems). They are the most common cause of P-lactam resistance. Most enzymes use a serine residue in the active site that attacks the P-lactam-amid carbonyl group. The covalently formed acylester is then hydrolyzed to reactivate the P-lacta-mase and liberates the inactivated antibiotic. Metallo P-lactamases use Zn(II) bound water for hydrolysis of the P-lactam bond. P-Lactamases constitute a heterogeneous group of enzymes with differences in molecular structures, in substrate preferences and in the genetic localizations of the encoding gene (Table 1). 

The basic reactions of the sol-gel procedure are shown in Eqs. (1-3), in which the species of Si—OH are the key intermediates. These Si—OH groups are known as Bransted acids. On the other hand, the amide carbonyl groups are... 

A process that is effective for epoxidation and avoids acidic conditions involves reaction of an alkene, a nitrile, and hydrogen peroxide.82 The nitrile and hydrogen peroxide react, forming a peroxyimidic acid, which epoxidizes the alkene, by a mechanism similar to that for peroxyacids. An important contribution to the reactivity of the peroxyimidic acid comes from the formation of the stable amide carbonyl group. 

The synthesis in Scheme 13.38 is based on an interesting kinetic differentiation in the reactivity of two centers that are structurally identical, but diastereomeric. A bis-amide of we.w-2,4-dimethylglutaric acid and a chiral thiazoline was formed in Step A. The thiazoline is derived from the amino acid cysteine. The two amide carbonyls in this to-amide are nonequivalent by virtue of the diastereomeric relationship established... 

In NRPs and hybrid NRP-PK natural products, the heterocycles oxazole and thiazole are derived from serine and cysteine amino acids respectively. For their creation, a cyclization (or Cy) domain is responsible for nucleophilic attack of the side-chain heteroatom within a dipeptide upon the amide carbonyl joining the amino acids [61]. Once the cyclic moiety is formed, the ring may be further oxidized, to form the oxazoline/thiazoline, or reduced, to form oxazolidine/thiazolidine (Figure 13.20). For substituted oxazoles and thiazoles, such as those... 

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