Amides from

I lagler A T, E Huler and S Lifson 1977. Energy Functions for Peptides and Proteins. I. Derivation of a Consistent Force Field Including the Hydrogen Bond from Amide Crystals. Journal of the American Chemical Society 96 5319-5327. 

Give off ammonia freely when treated with aqueous NaOH solution in the cold (distinction from amides, imides and nitriles). 

The reaction is applicable to the preparation of amines from amides of aliphatic aromatic, aryl-aliphatic and heterocyclic acids. A further example is given in Section IV,170 in connexion with the preparation of anthranilic acid from phthal-imide. It may be mentioned that for aliphatic monoamides containing more than eight carbon atoms aqueous alkaline hypohalite gives poor yields of the amines. Good results are obtained by treatment of the amide (C > 8) in methanol with sodium methoxide and bromine, followed by hydrolysis of the resulting N-alkyl methyl carbamate ... 

Hydrolysis may be effected with 10-20 per cent, sodium hydroxide solution (see p-Tolunitrile and Benzonitrile in Section IV,66) or with 10 per cent, methyl alcoholic sodium hydroxide. For diflScult cases, e.g., a.-Naphthoniirile (Section IV,163), a mixture of 50 per cent, sulphuric acid and glacial acetic acid may be used. In alkahne hydrolysis the boiling is continued until no more ammonia is evolved. In acid hydro-lysis 2-3 hours boiling is usually sufficient the reaction product is poured into water, and the organic acid is separated from any unchanged nitrile or from amide by means of sodium carbonate solution. The resulting acid is identified as detailed in Section IV,175. 

Q or Br designates the corresponding a-chloro or a-brorao-aldehyde or ketone PjS5 designates thioanrides formed in situ from amides. 

When chloroacetaldehyde is condensed with higher thioamides prepared from amides and phosphorus pentasulfide according to Schwarz s method (222), 2-substituted thiazoles are obtained (4, 10,"22, 175). 

IS general for nucleophilic acyl substitution and well worth remembering The range of reactivities is quite large a factor of about 10 m relative rate separates acyl chlorides from amides... 

Specialty Isocyanates. Acyl isocyanates, extensively used in synthetic appHcations, caimot be direcdy synthesized from amides and phosgene. Reactions of acid haUdes with cyanates have been suggested. However, the dominant commercial process utilizes the reaction of carboxamides with oxalyl chloride [79-37-8]. CycHc intermediates have been observed in these reactions which generally give a high yield of the desired products (86). 

Table 2. Comparative Yields of Esters from Amides or Acids...

ROBINSON - GABRIEL OxazoleSynthesis Oxazole synthesis from amides of a-aminoketones... 

SONN MULLER Aldehyde synthesis Aldehyde synthesis from amides or ketoximes, by reduction of irmno chiondes. 

Both methods of nitrile synthesis—SN2 displacement by CN- on an alkyl halide and amide dehydration—are useful, but the synthesis from amides is more general because it is not limited by steric hindrance. 

When a cold (-78 °C) solution of the lithium enolate derived from amide 6 is treated successively with a,/ -unsaturated ester 7 and homogeranyl iodide 8, intermediate 9 is produced in 87% yield (see Scheme 2). All of the carbon atoms that will constitute the complex pentacyclic framework of 1 are introduced in this one-pot operation. After some careful experimentation, a three-step reaction sequence was found to be necessary to accomplish the conversion of both the amide and methyl ester functions to aldehyde groups. Thus, a complete reduction of the methyl ester with diisobutylalu-minum hydride (Dibal-H) furnishes hydroxy amide 10 which is then hydrolyzed with potassium hydroxide in aqueous ethanol. After acidification of the saponification mixture, a 1 1 mixture of diastereomeric 5-lactones 11 is obtained in quantitative yield. Under the harsh conditions required to achieve the hydrolysis of the amide in 10, the stereogenic center bearing the benzyloxypropyl side chain epimerized. Nevertheless, this seemingly unfortunate circumstance is ultimately of no consequence because this carbon will eventually become part of the planar azadiene. 

Syntheses starting from amides of 2-aminobenzoic acid and 2-aminobenzophenone derivatives are also known.34,35... 

As the formation of betaines from amide-stabilized ylides is known to be reversible (in contrast with aryl- or semistabilized ylides, which can exhibit irreversible anti betaine formation see Section 1.2.1.3), the enantiodifferentiating step cannot be the C-C bond-forming step. B3LYP calculations of the individual steps along the reaction pathway have shown that in this instance ring-closure has the highest barrier and is most likely to be the enantiodifferentiating step of the reaction (Scheme 1.16) [25]. 

In general, the rate of syn/anti equilibration increases with decreasing basicity of the enolate and with increasing steric repulsion in the enolate. The first point is illustrated by the fact that aldolates derived from ketones (X = aryl, alkyl) undergo syn/anti equilibration more readily than those derived from amides or carboxylates (X = NR2,0-). It appears that the rate of the retro-aldol addition is higher when the enolate thereby generated is more stable. 

Fig. 34. Preparation of acylureas from amides with BTMA Br3 BTMA Brj, DBU, R -OH...

Fig. 35. Preparation of methyl carbamates from amides with BTMA Br3...

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