Acidity imides

Clearly, in the case of (66) two amide tautomers (72) and (73) are possible, but if both hydroxyl protons tautomerize to the nitrogen atoms one amide bond then becomes formally cross-conjugated and its normal resonance stabilization is not developed (c/. 74). Indeed, part of the driving force for the reactions may come from this feature, since once the cycloaddition (of 72 or 73) has occurred the double bond shift results in an intermediate imidic acid which should rapidly tautomerize. In addition, literature precedent suggests that betaines such as (74) may also be present and clearly this opens avenues for alternative mechanistic pathways. 

Acylation of l,2,4-triazolo[l,5-c]quiiiazoliii-5-oiie (141) with ethyl chlo-roformate occurred at N6 to afford the 6-ethoxycarboiiyl derivative 142 (75CB3799) (Scheme 55). Tliis result indicates that the amide tautomer (lactam tautomer) 141 prevailed over the corresponding imidic acid tautomer (lactim tautomer). 

In the presence of potassium carbonate, alkyl halides reacted with the imidic acid tautomers 154 of l,2,4-triazolo[l,5-c]pyrimidin-2-ones (153) to afford the 2-alkoxy derivatives 155 (85USP4528288 94JMC2371) (Scheme 60). 

Tlie infrared spectra revealed the dominance of the 2-oxo (153) and 5-0X0 (157) structures (amide or lactam tautomers) over the 2-hydroxy (154) and the 5-hydroxy (192) structures (imidic acid or lactim tautomers)... 

C13H17NO 63367-12-4) see Ibuprofen a-hydroxy-a-methyl-4-(2-methylpropyl)benzeneethan-imidic acid methyl ester hydrochloride... 

Alternatively, the imide-acid chloride is reacted with methanol to give the imide ester which, after borohydride reduction and triethylsilane/trifluoroacetic acid treatment, furnishes the bicyclic lactam 6 as a racemate. The latter is acylated with either propanoyl chloride or 3-phcnylpropanoyl chloride and the resulting amides 7 deprotonated and alkylated with (bro-momethyljbenzene or iodomethane, respectively, to give the major alkylation products 8 with d.r. >98 2 and in 65% yield3. 

Base-catalysed hydrolysis. The hydroxide ion attacks the nitrile carhon, followed hy protonation on the unstable nitrogen anion to generate an imidic acid. The imidic acid tautomerizes to the more stable amide via deprotonation on oxygen and protonation on nitrogen. The base-catalysed amide is converted to carboxylic acid in several steps as discussed earlier for the hydrolysis of amides. 

Observations -Substituted imide acid esters were prepared by the nucleophilic attack... 

Imidic acid (40) is the lactim tautomer of an acid amide (39 lactam form). Although no substantiated claim has been put forward for the isolation of free imidic acids, imidates (41) (also... 

Reversed phase Amines, amides, imides, acids, profens a-Hydroxy acids, oxazolidinones, amino acids, peptides a-Hydroxy acids, acids, profens, amino acids, amino esters, hydantoins, peptides... 

Nitriles are susceptible to hydrolysis via nucleophilic attack of water on the electropositive carbon atom, especially under strongly acidic and basic conditions (Fig. 29). Nitriles hydrolyze to imidic acids, which tautomerize to amides. Amides can be hydrolyzed further to carboxylic acids, although much more slowly. Nitriles are susceptible to oxidation by peroxides under mildly basic conditions (e.g., pH 7.5-8) as has been documented in the case... 

Solid acids or bases often play a catalytic role in the activation of an oxidant such as H2O2. Although this topic is not discussed in detail here, we nevertheless illustrate it with two examples. First, LDHs can function as solid bases to catalyze the conversion of aromatic nitriles to peroxy-imidic acids the latter are excellent stoichiometric oxidants for olefin epoxidation (393) ... 

Figure 7.2 illustrates the phosphorus pentoxide-mediated dehydration of a primary amide to a nitrile, using the transformation of nicotine amide (A) into nicotine nitrile (B) as an example. The reaction of phosphorus pentoxide at the carboxyl oxygen furnishes the partially ring-opened iminium ion E (simplified as F) via the polycyclic iminium ion C. E is deprotonated to give the mixed anhydride G from imidic acid and phosphoric acid. Imidic acids are characterized by the functional group R-C(=NH)-OH. This anhydride is transformed into the nitrile B by an El elimination via the intermediate nitrilium salt D. Nitrilium salts are iV-pro-tonated or V-alkylated nitriles. 

The total hydrolysis of phenylacetonitrile (Formula A in Figure 7.9) to phenylacetic acid (C) can be performed in one or two steps and both under acidic (following the mechanism in Figure 7.8) and basic conditions. In the latter case, the nucleophilic addition of a hydroxide ion to the nitrile carbon atom is the rate-determining step. This is how the imidic acid anion D is formed. Protonation (—> F), deprotonation (—> E) and reprotonation yield the amide B, which one can isolate or further hydrolyse under harsher conditions via the usual BAC2 mechanism (cf. Figure 6.24). 

Fig. 7.13. Mechanism of the Pinner alcoholysis of nitriles— via the (possibly) isolable imidic acid ester hydrochloride (B)—to carboxylic acid esters.

Side Note 7.2. Chemistry of Imidic Acid Ester Hydrochlorides Preparation of Orthoesters and Amidines... 

Abb. 7.14. Imidic acid ester hydrochlorides (F)—to be prepared from nitriles, hydrogen chloride (gas) and methanol acc. to Fig. 7.13—, their trans-formability into orthoester (A) or amidine (I) and the corresponding reaction mechanisms. 

C,H]7NO 63367-12-4) see Ibuprofen cx-hydroxy-a-methyl-4-(2-methylpropyl)benzeneethan-imidic acid methyl ester hydrochloride (C 4H22C1N02) see Ibuprofen 2-hydroxymethyl-5-methylpyrazine (C,H8N20 61892-95-3) see Acipimox... 

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