Hydrolysis of substituted amides

Hydrolysis of primary amides cataly2ed by acids or bases is very slow. Even more difficult is the hydrolysis of substituted amides. The dehydration of amides which produces nitriles is of great commercial value (8). Amides can also be reduced to primary and secondary amines using copper chromite catalyst (9) or metallic hydrides (10). The generally unreactive nature of amides makes them attractive for many appHcations where harsh conditions exist, such as high temperature, pressure, and physical shear. 

Reaction 12, the acid-catalyzed hydrolysis of substituted benzamides, has p = — 0.22, so the reaction is modestly facilitated by electron-donating groups. This suggests that protonation of the amide is kinetically important ... 

The addition of Grignard reagents to isocyanates gives, after hydrolysis, N-substituted amides. This is a very good reaction and can be used to prepare derivatives of alkyl and aryl halides. The reaction has also been performed with... 

Fig. 4.2. The effect of chain length (li) on the degree of hydrolysis [%] of primary amides by rat liver preparations (5 h at pH 7.4). Black bars amides of normal saturated fatty acids hatched bar isohexanamide unshaded bars amides of m-phenyl-substituted saturated fatty...

N-Methyl substitution does not seem to influence dramatically the hydrolysis of the amide bond. Indeed, a similar relationship between hydrolysis and chain length has been described for unsubstituted aliphatic amides... 

Solvolysis of urea analogues (200) in aqueous KOH leads to hydrolysis of the amide rather than substitution at nitrogen, in keeping with the poor leaving capacity of alkox-ide (equation 28). This reaction is an excellent source of Af,Af-dialkoxyamines (203), a relatively little known class of compounds . 

The sulfonamide 364 was obtained from the reaction of 2-nitrobenzenesulfonyl chloride 362 and the substituted anilines 363, which were then converted to the 1,2,5-thiadiazepines 365 by refluxing 364 with copper, followed by hydrolysis of the amide (Scheme 75) <2004H(63)2457>. 

Substitutionally inert Co(m) or Ir(m) complexes have been used to measure directly the effect of Lewis acid activation on the hydrolysis of an amide [35-37], a nitrile [38] and a phosphate triester [39] (Figure 6.4). The p/C, of the cobalt-bound water molecule in 5 is 6.6 [40], Thus the upper limit for the rate-acceleration due to Lewis acid activation with this metal in the hydrolysis of esters, amides, nitriles and phosphates should be close to 109-fold. Although the observed rate accelerations for the hydrolysis reac-... 

Hydrolysis of the amide forms the Friedel-Crafts substitution products. 

Substituted Amides. The identification of substituted amides is not easy. There are no completely general tests for the substituted amide groups and hydrolysis is often difficult. 

The acylation is a straightforward nucleophilic substitution at the carbonyl group and the CFj>. group is chosen to make the anion at nitrogen more stable. Alkylation can occur only once wherea direct alkylation with Mel could occur several times. Hydrolysis of the amide is also easier with .. CF3CO group. 

Under these conditions the esterification of the free alcoholic fimctions occurs together with the substitution of the hemiacetalic hydroxyl at C-2 with chlorine, which occupies the less hindered axial position owing to its steric requirements. The obtained methyl-tetraacetyl-2P-chloro sialoside 2h reacts with methanol in the presence of silver caifionate to give, via a bimolecular nucleophilic substitution, the methyl tetraacetyl-2a-methoxy sialoside 2i. In the presence of catalytic quantities of potassium r-butoxide a rapid transesterification of 2i with methanol, allows to obtain methyl 2a-methoxy sialoside 3a in very high yields, without hydrolysis of the amidic linkage at C-4. 

Although much of the work of the past few years has suggested that the acid-promoted hydrolysis of phosphinic amides proceeds by a continuous spectrum of mechanisms ranging from direct nucleophilic substitution to unimolecular dissociation, depending upon the nucleophilicity of the leaving group and the nature of the... 

Figure 3. (a) Electrophilic substituted alkenes, and (b) Taft a LFER for alkaline hydrolysis of primary amides. From Wolfe (1980b) with permission of Butterworth Publishers. 

As part of our research work to achieve new, simple, non corrosive and environmentally friendly processes for the acid hydrolysis of aromatic amides, we report herein a study of the hydrolysis of substituted anilides (Scheme 1) in liquid phase using zeolites with different pore structures and framework Si-to-Al ratios, as acid catalysts. 

Rates of hydrolysis of substituted aromatic amides by the bacterial population of pond water correlated well with the infrared C=0 stretching frequencies of the substrates (Steen and Collette 1989). 

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