Water, amide reactions

Reaction with water to yield a carboxylic acid Reaction with an alcohol to yield an ester Reaction with ammonia or an amine to yield an amide Reaction with a hydride reducing agent to yield an aldehyde or an alcohol... 

As well as in water, the reaction can be carried out in ammonia or in an alcohol when addition again takes place across the C=C bond of the ketene to yield an amide or an ester, respectively, of the homologous acid. 

On the first full-scale run of a modified process for the nickel catalysed isomerisation of the oxime to the corresponding amide, on 1200 kg scale in toluene solution under reflux in place of the previous water, the reaction overheated (to >180°C), pressurised, and then escaped confinement. Investigation showed the explosion to be purely a runaway reaction caused by a slower start than previously. It was recommended that the oxime be charged in portions, and the solvent changed to the higher-boiling xylene. 

Amidation. Reactions leading to the formation of amides R-C-NH2. Examples include the dehydration (water removal) of the ammonium salts... 

Most of the now synthetically used quantitative cascade reactions involve an initial substitution step. That is quite clear for the reactions of acyl hahdes with thioureas to give 2-aminothiazoliiun salts. The 3-cascade consists of substitution to form the thiuronium salt, specific cychzation with the more nucleophihc of the amino groups, and elimination of water. In all reported cases, the water of reaction is taken up by the product crystal and it can be removed by heating to about 80 °C in a vacuiun. For example, if the thioureas 162 and phenacyl bromide 217 are stoichiometrically ball-milled at room temperature for 30 min, quantitative yields of the pure products 428 are obtained in all cases after drying at 0.01 bar at 80 °C [ 10] (Scheme 67). The free bases 429 can be obtained by trituration of 428 with NaHCOj solution. Furthermore, the thioureido-acet-amides 275 react correspondingly with 217 to give quantitative yields of the salts 430 from which the free bases can be obtained by NaHCOj trituration [96]. 

These can be explained if they involve a third reaction of the protonated ester, i.e. with a molecule or molecules of water, a reaction not, of course, observed in media such as SbF5-FS03H. The activity of water falls rather sharply as the sulphuric acid concentration increases from 60-100%, and we know that most esters become essentially completely protonated in this region. Thus the situation can arise where the increase in the concentration of protonated ester produced by a given increase in acid concentration is proportionately smaller than the concomitant decrease in the activity of water, so that bimolecular (or higher molecularity) hydrolysis goes more slowly as the acidity is increased. Similar behaviour is observed when amides are hydrolyzed in strong acid solutions, but the rate maximum occurs at lower acid concentration, since amides are more basic than esters, and protonation is complete in solutions of lower acidity. 

Acid-catalyzed addition of water to an amide, though itself a slow reaction, is inherently faster than acid-catalyzed addition of water to a nitrile, even though the equilibrium constant for the latter reaction is much less unfavorable. This is again a result of the difference in angular distortion see Fig. 9. For the amide reaction, the distortions are the same as for the ester example above three times... 

The amide 2 is paracetamol, the popular analgesic. Amines are much more nucleophilic than phenols (compare the basicities of ammonia and water) so reaction with acetic anhydride gives... 

Esters and amides, on the other hand, require the presence of an acid or base catalysis to react with water. These reactions are not instantaneous but require rather strongly acidic or basic conditions and heat to proceed at a reasonable rate. For example, a typical ester saponification is usually conducted with 10% NaOH in water, and the solution is refluxed until the ester layer disappears. (Most esters are not soluble in water.) This may require from 15 minutes up to several hours of reflux. Similarly, a typical amide hydrolysis is often conducted by refluxing the amide in concentrated hydrochloric acid for a period ranging from 15 minutes up to several hours. Esters and amides are relatively stable to the near-neutral conditions found in living organisms, which is one reason why they are important functional groups in biochemistry. 

Nitriles can be prepared by dehydration of primary amides (reaction 8) or of aldoximes (reaction 9), catalyzed by the Re trioxo compounds [ReOsX] (X = OSiMes, OReOs, OH) in azeotropic (e.g. toluene/water or mesitylene/water) reflux. Aqueous perrhenic acid (X = OH) is the most convenient catalyst in view of the moisture sensitivity of the others. The oxophilicity of the Re(VII) oxo-complexes is believed to play a determining role in the reactions, which are proposed to involve six-membered cyclic transition states formed upon preferential (9-coordination, relative to A-coordination, of the amide or oxime. ... 

Water-soluble carbodiimide for die modification of carboxyl groups in proteins zero-length crosslinking proteins activation of carboxyl groups for amidation reactions, as for the coupling of amino-nucleotides to mattices for DNA microarrays. 

Chlorodiphenylacetonitrile formed tetraphenylsuccinonitrile as well as a diflFerent type of complex. The infrared spectrum of the latter contained no nitrile absorption band (2210 cm." ) but exhibited a cyanide stretch at 2130 cm. S characteristic of inorganic pentacyanocobaltate(III) complexes 14,22), and a carbonyl band at 1575 cm. Its PMR spectrum indicated the presence of the (C6H5).)CH group. Diphenylacetamide precipitated on heating an aqueous solution of the complex. Apparently the resonance-stabilized radical initially formed in the reaction of this a-halonitrile with pentacyanocobaltate(II) may either dimerize or combine with pentacyanocobaltate(II) to form an N-keteniminocobalt complex. The latter is unstable in water, being converted to an N-amido-cobalt complex, which may be further hydrolyzed to the free amide (Reaction 23, paths d and e). Presumably the radical cannot add penta-... 

The advantage of glycamine over glycosylamine is that the former is more stable during the amidation reaction to form neoglycoproteins, typically using water soluble carbodiimide at pH 4-5. Glycamines have also been used to modify poly-carboxylic compounds, such as poly-Asp or poly-Glu [26,28]. 

ZINC BUTTER or ZINC CHLORIDE or ZINC (CHLORURE de) (French) (7646-85-7) ZnCl2 Noncombustible solid. Reacts with water, forming a medium-strong acidic solution (pH about 4) zinc oxychloride may be formed with large amounts of water. Violent reaction with strong bases, amines, amides, and inorganic hydroxides potassium. Attacks metals as fume or in the presence of moisture. Thermal decomposition forms toxic zinc oxides and hydrogen chloride fumes. 

Ammonium carbamate is a constituent of commercial ammonium carbonate. The salts of carbamic acid are hydrolyzed by boiling with water, the reaction being analogous to that with other amides —... 

The reaction, referred to as amidation, is a reversible reaction. Amide formation is maximized by forcing the equilibrium to the right by removal of water via running the reaetion above the boiling point of water. Amide formation is the reaction by which polypeptides and proteins are synthesized in biologieal systems. 

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