Amide isomers

Amides and carbaminates are a further class of substrates [255, 274-278], Compound 114 shows a substrate with an unprotected hydroxyl group and an aryl iodide [279] (Scheme 1.50), 116 an aryl iodide and the competition of an amide with an amine, yielding a 2.5 1 mixture of amide isomers favoring the (Z)-amide configuration depicted in 117 [280] (Scheme 1.51). 

Fig. 9 Amide isomers isolated from pupae of Epilachna borealis...

The major components are series of homologous trimers, tetramers, and pentamers of the three acids 44-46, along with smaller quantities of dimers, hexamers, and heptamers. Furthermore, the secretion contains several isomers of each oligomer, furnishing a combinatorial library of several hundred macro-cyclic polyamines [51, 52]. Using repeated preparative HPLC fractionation, the most abundant trimeric, tetrameric and pentameric earliest-eluting compounds were isolated. One and two-dimensional H NMR spectroscopic analyses showed that these molecules were the symmetric macrocyclic lactones 48, 49, and 50 (m, n, o, p, q=7) derived from three, four or five units, respectively, of acid 46. Moreover, using preparative HPLC and NMR methods, various amide isomers, such as 53,54, and 55 (Fig. 9) were also isolated and characterized [51,52]. 

In contrast with the oxocarboxylic acids, which readily participate in tautomeric equilibria in solution, their open-chain and cyclic N-unsubsti-tuted and A-monosubstituted amide isomers are more stable. In most cases, the tautomeric equilibrium (Scheme 3) is not observed in neutral aprotic solvents at ambient temperature. In protic solvents, e.g., CD3OD, intercon-... 

Beckmann rearrangement of ketoximes is achieved efficiently with anhydrous FeCls in the absence of solvent. The rearrangement was selective, producing only one amide isomer in usually good yield. 

It is therefore not possible to form the anti-amide 208 unless conformational changes at the nitrogen are allowed. It is however reasonable to make such an assumption for formamide-derived tetrahedral intermediates (cf p. 112). We can therefore analyze the cleavage of a tetrahedral conformer such as 213. This conformer can either give the anti or the syn-amide isomers (208 and 209) with stereoelectronic control. It is however not clear on that basis, why the formation of the less stable anti form 208 is favored. There must be another parameter in this case which is not known yet. 

Surprisingly, some 2,3,6-substituted pipecolic acid derivatives like 2 favor exclusively the anti amide isomer [19]. The anti preference of 2 has been demonstrated by NMR spectroscopy in solution (methanol and DMSO) and X-ray analysis in the solid state. The reason for this unexpected finding is the special arrangement of substituents on the pipecolic heterocycle. In contrast to compounds like 1, the additional bulky substituent attached to C3 forces the carboxy group at C2 into an equatorial position and the substituent at C6 into an axial position. 

Compare A/-methylacetamide (see the preceding paragraph) with its amide isomers propanamide and A/,A/-dimethylformamide. Which do you predict has the highest boiling point The lowest ... 

There are four amide isomers with the molecular formula C3H7NO. Draw their condensed structural formulas and give the lUPAC name for each. (14.6)... 

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