Amide group rearrangement

Carboxylic acid, 161, also serves as starting material for a substituted pyrazine that has proven to be an important diuretic agent. As the first step in the synthesis the acid is converted to the corresponding amide (165). Treatment with a single equivalent of hypobromous acid effects Hoffmann rearrangement of only one of the amide groups. Ethanolysis of the intermediate carbamate leads directly to the amino ester (166). Exposure of the... 

A potential versatile route into a-amino acids and their derivatives is via a combination of (i) nitrile hydratase/amidase-mediated conversion of substituted malo-nonitriles to the corresponding amide/acid followed by (ii) stereospecific Hofmann rearrangement of the amide group to the corresponding amine. Using a series of a,a-disubstituted malononitriles 14, cyanocarboxamides 15 and bis-carboxamides 16, the substrate specificity of the nitrile hydratase and amidase from Rhodococcus rhodochrous IF015564 was initially examined (Scheme 2.7). The amidase hydrolyzed the diamide 16 to produce (R)-17 with 95% conversion and 98%e.e. Amide 17 was then chemically converted to a precursor of (S)-a-methyldopa. It was found... 

Although iodine(III) reagents attack double bonds, the rearrangement of the amide group is, at least in some cases, more rapid than electrophilic attack on alkenes. Thus 3-cyclohexene-l-carboxamide rearranges smoothly to the corresponding amine as long as only one equivalent of [1,1-bis(trifluoroacetoxy)iodojbenzene is used. 

Cyclization of benzophenones having an o -thioacetic acid, ester or amide group has been used in structure studies and to synthesize 3-phenylbenzo[6 ]thiophenes with specific substituents. Thus (57) was readily converted to (58 X = OH, OEt or NH2) as precursors to a variety of benzo[6 ]thiophenes (57AC(R)705>, and as precursor to the unequivocal synthesis of 3-phenylbenzo[6 jthiophene, to demonstrate a remarkable sulfur-catalyzed rearrangement (59AJC218). 

This chemistry can be very powerful, since the amide product itself offers further possibilities for functionalisation by lithiation. The synthesis of the natural product ochratoxin A (section 9.1) illustrates this point. Two successive ortholithiations of carbamate 210 are used first to introduce one amide group and then a second, by anionic ortho-Fries rearrangement. The symmetrical diamide 211 can be allylated and then cyclised in acid, with concomitant hydrolysis of the second amide and deprotection of the phenol to yield a known intermediate... 

Direct allylie animationS8,89 is achieved by reaction of 3-cyclohexene-l-carboxylic esters or amides 1 with bis(A -4-toluenesulfonyl)sulfodiimide in an ene reaction, followed by a sigmatropic rearrangement. The regioselectivity of the first step, i.e., the ene reaction, is governed by steric factors of the ester or amide group. The methyl ester gives a 3 2 ratio (80% yield) and the ter -butyl ester a 3 1 ratio (70%), but the bulky TV.A -dicyclohexylamide furnishes a 20 1 ratio of the 5-tosylamino 3 and 2-tosylamino isomers 2 (32% yield). 

Amide group scission (termed as cA-elimination mechanism) and intramolecular rearrangement of two amide groups, leading to cyclic compounds [20] are the main pyrolysis reactions in acyclic polyamides. The former reaction is outlined in Scheme 12.1b and the ester exchange drawn in Scheme 12.2 is analogous to the latter one. 

Details are lacking, but the amide group apparently does not interfere with LiC104-catalyzed rearrangement of compound (159 equation 66), which gave the same product as BF3 catalysis. ... 

---