Aromatic amides, hydrolysis

With aromatic amides, hydrolysis prior to rearrangement may occur to such an extent that the yield is lowered seriously. Amides like p-nitrobenzamide, having a substituent which withdraws electrons from O... 

The characterisation of a primary aromatic amide is based upon its own m.p. and the identification of the acid (see Section IV,175) produced on hydrolysis. A crystalline derivative may be prepared directly with xanthhydrol (for experimental details, see Section 111,110, 1). 

An example will show the nature of electrical effects (resonance and field) on reactivity. In the alkaline hydrolysis of aromatic amides (10-11), the rate-determining step is the attack of hydroxide ion at the carbonyl carbon ... 

In rats dosed orally with the insect repellent N,N-diethyl-2-phenylacet-amide (4.57), TV-ethyl-2-phenylacetamide (4.58), 2-phenylacetamide (4.59), and 2-phenylacetic acid (4.60) were found as metabolites in the blood, liver, and kidney [35], Hydrolysis of this tertiary amide is, perhaps, facilitated by the presence of the aromatic ring. Indeed, a similar metabolic pattern has been found for the aromatic amide TV,TV-diethyl-3-methylbenz amide (4.82) (see Sect. 4.3.1). 

Reaction XCVII. Hydrolysis of Amides, Acid Chlorides and Acid Anhydrides. (A., 188, 73 B., 26, R 773 28, R., 917, 32, 1118.)—All these compounds on hydrolysis yield acids. The anhydrides are hydrolysed by treatment with water or dilute alkali, the acid chlorides are usually very rapidly hydrolysed by water, but in the aromatic series 10% caustic alkali is sometimes necessary. The amides are boiled with caustic alkali solution (10%) or with cone, hydrochloric or sulphuric acid. They are, especially the substituted aromatic amides, very resistant to the action of acids, so that the former method is the best. Another method is to dissolve the amide in cone, sulphuric acid, and add sodium nitrite in the cold, afterwards gently warming. Sometimes dilute sulphuric acid and addition of the nitrite in the warm gives better results. 

Introduction of RLi-unreactive silicon substituents has advantages in protection of Ar-C-H and Ar-CH3 sites. Thus taking advantage of the cooperativity of amide and methoxy DMG, metalation-silylation followed by metalation-E+ quench affords, after fluoride-mediated desilylation and amide hydrolysis, a route 1,2,5-substituted benzoic acids, 18 —> 19 (Scheme 5). Lateral metalation, of considerable utility in post-DoM chain extension [19], followed by double silyla-tion and further DoM-E+ quench and the same fluoride and acid treatment steps, furnishes 1,2,3,4-tetrasubstituted aromatic compounds, 20 —> 21 [10, 20],... 

From the comparative experiments in DjO the catalysis by the cyclic dipeptides was confirmed to be nucleophilic, which is the same as the imidazole catalysis. It is seen in Table 16 that in the hydrolysis of PNPA kc for the cyclic peptides is onfy 1/10-1/5 as much as that for imidazole. The lower reactivity of the cyclic dipeptides is explained partly in terms of the lower pKj values and partly because of the larger steric hindrance for the nucleophilic reaction. Only when the pattern of the substrate binding—intramolecular catalysis of the cyclic peptides excels the decrease of basicity and the increase of steric hindrance, an enhanced catalysis by the cyclic dipeptides is possible. With regard to an increase of reactivity was expected for the hydro-phobic interactions by a sli tly larger acyl chain and for the aromatic-amide interaction (see Sections 3.3 and 3.6) between the p-phenyl group of the substrate and... 

Alternatively, applying basic reaction conditions, partial hydrolysis with hydroxide-loaded anion exchangers in boiling water leads to aromatic amides in good yield. " ... 

Amide hydrolysis is a key step in the widespread strategy of protection/deprotection of amino groups for synthetic purposes, usually carried out in homogeneous phase with mineral acids. It is shown here that under mild conditions (batch reactor, liquid phase, 75°C) large pore zeolites (HY, HBeta, HMOR) can catalyse the hydrolysis of various aromatic amides. The best results are obtained over HY zeolite samples with Si/Al ratios of 16 and 30 e.g. complete and selective hydrolysis of 2-nitroacetanilide after 2-4 hours reaction for a zeolite/substrate ratio of 0.5 g/mmol. For similar values of the Si/Al ratio HBeta and rather all HMOR samples are much less active than HY samples, which is probably related to diffusion limitations. 

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. 

The influence of the solvent was studied for the hydrolysis of 2-, 3- and 4-nitroacetanilide using an HY zeolite (Si/Al=30) as catalyst. From Table 1 it can be seen that the reaction rate was higher when a mixture of methanol-water (1 1) was used as solvent than with methanol or with water separately. The slower hydrolysis rate in water, when compared to methanol or to methanol-water, can be explained by the lower solubility of the aromatic amides. The hydrolysis in the presence of methanol could be due to the small amounts of water present in the commercial synthesis grade methanol used. While this is enough to accomplished the reaction, methanolysis cannot be ruled out. 

Since, in homogeneous catalysis, the chemical nature of the amine moiety has a large influence on the hydrolysis rate [2,6,7], the previous conditions with zeolites were applied to several aromatic amides containing different substituents and to benzanilide. 

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