Amide tautomerization

In the third transition state (TS3), the neutral catalyst is recovered by transferring the proton back from the catalyst to the substrate. In other words, the (former) azlactone ether oxygen atom deprotonates the tertiary ammonium ion. For proton transfer, again an LBHB is formed (N-0 distance 2.479 A, <(0,H,N)=166.2°). In the product complex, the catayst is neutral and the A-acylamino acid ester is bound in its iminol form to the catalyst (Product(iininol)). Finally, an additional 66.6 kJ moF are gained by the subsequent iminol-amide tautomerization (Product(ainide)) (Fig. 1). 

This compound is a tautomer of an amide. Tautomerization occurs in the same manner as was the case for the conversion of an enol to its carbonyl tautomer. 

The infrared absorption spectrum of sulfacetamide sodium has been determined in KBr disc (4). The principal peaks appear at 825, 1090,1145,1264,1552,1600 cm 1. The infrared stretching frequencies of the amino group have been used to calculate the force constant, the band angle and the "S" character of the nitrogen orbitals of the N-H band (23,24). Infrared measurements of sulfonamides have been performed to study the imide-amide tautomerism (25) and to see if there is any change in the electronegativity of the SO2 group (26,27). Sulfacetamide in eye-drops and ointments has been identified by attenuated total reflectance (ATR) infrared spectra (28). 

Initially, Passerini proposed that the reaction involved an addition of carboxylic acid to carbonyl compound, giving acyloxy hemiacetal, which then reacted with isonitrile to form the final product. However, current views about this reaction favor the following consecutive processes the protonation of the carbonyl compound from carboxylic acid, followed by the attack of isonitrile to give a nitrilium ion, the nucleophilic addition of carboxylate, acyl group transfer, and the final amide tautomerization. A general mechanism for this reaction is shown here. ... 

Sulfasalazine (5-[4-[(2pyridylideneamino)sulfonyl]phenyldiazenyl]salicylic acid) (40) was first isolated in triclinic form and it was shown by X-ray analysis that the molecule is present in the amide tautomeric form 40c (2001ACX435). Later it was isolated in monoclinic form, and this form was shown by X-ray analysis to exist in the imino form 40d (Scheme 31) (2005AXCo226). 

Two different reaction pathways have been h5q>othesized for the Passerini reaction the first one is supposed to be ionic (Fig. 5.1) the second one, concerted (Fig. 5.2). In polar solvents such as methanol or water, the reaction proceeds hy protonation of the carbonyl followed by nucleophilic addition of the isocyanide to produce the nitrilium ion, 3 (below). Addition of a carboxylate gives the intermediate, 4. Acyl group transfer and amide tautomerization yield the desired ester, 5. 

These compounds exempHfy a type of vinylogous iminol-amide tautomerism in which both tautomers, except for 23, are conjugated chelates (Figure 11.8). Compounds 19-23 have been examined by both experimental and computational means [32], the LSER study being pubhshed separately [33]. Dudek and Dudek [34] studied tautomerism in some Schiff bases, one of which is 24, but while these... 

With an unbalanced data set such as that of Table 5.5 no great reliance can be placed on the coefficients of Eq. (5.20) but the conclusions which matter, that both (7[ and (jg are important but the second more so, are probably valid nevertheless. The evidence regarding amide tautomerism is of a different sort. While R for 2-pyridones 39 is dominated by ff[, as is the 2(6)-position of 4-pyridone, it is generally true for any other type of position in any other oxoheterocycle, which has been examined that, where there are enough data to work on, will be the a-constant that gives the best fit [1]. A particularly good example Is provided by R... 

The reaction of thioethers with ethyleneimine in the presence of acid yields sulfonium compounds. The reaction is reversible under alkaline conditions (125). Compounds in which double-bonded sulfur can exist in tautomerism with a form having a free SH group, such as thiourea (126,127), thiocarboxyhc acids (128), and thiophosphates (129), react to give aminoaLkylated products. The P-aminoethyl thiocarboxylate rearranges to give the amide. 

Many of the physical properties of fatty acid amides have been explained on the basis of the tautomeric stmctures ... 

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. 

No simple pteridine 1- or 3-oxides are yet known. If the AT-atom of an amide function is formally oxidized, tautomerism favours the cyclic hydroxamic acid structure, as found for 3-hydroxypteridin-4-one (55JA3927), 1-hydroxylumazine (64JOC408) and 2,4-diamino-8-hydroxypteridin-7-ones (75JOC2332). 

The sulfur atom can be used to initiate C—C bond formation. 2-Thio- and 4-thio-6,7-diphenyllumazine (166) react with phenacyl halides to give the phenacylthio derivatives (167), which on heating in DMF in the presence of triphenylphosphine extrude sulfur to form the benzoylmethyl derivative (168) in its tautomeric vinylogous amide form (169 equation 51). 

Structural analogy of aliphatic amino ketones can be found in the heterocyclic series. A simple example of such compounds is /) -octahydro-7-quinolone (767) which, as a vinylog of an amide, can possess enonamine-enolimine tautomerism (168). 

The whole concept of direct methylation has recently been critically reviewed and rejected by Gompper as a method to study tautomerism. The difference in the proportions of the two methyl derivatives produced w hen diazomethane is in excess, or the reverse, has now been ascribed to the relative importance of the Sn and Sn reactions of the tautomeric compound with diazomethane. The proportions of N- and 0-methyl derivatives formed by the reaction of cyclic amides with diazomethane has been related to the infrared vC—O frequencies. ... 

Although these reactions suggest the possibility of a tautomeric equilibrium between the amide and imidol forms in the A -unsub-stituted compounds, the ultraviolet,fluorescence, and infrared spectra of a series of such compounds support the amide structure only. 

Quinoxalin-2-ones are in tautomeric equilibrium with 2-hydroxy-quinoxalines, but physical measurements indicate that both in solution and in the solid state they exist as cyclic amides rather than as hydroxy compounds. Thus quinoxalin-2-one and its A -methyl derivative show practically identical ultraviolet absorption and are bases of similar strength. In contrast, the ultraviolet spectra of quinoxalin-2-one and its 0-methyl derivative (2-methoxyquinoxaIine) are dissimilar. The methoxy compound is also a significantly stronger base (Table II). Similar relationships also exist between the ultraviolet absorption and ionization properties of 3-methylquinoxalin-2-one and its N- and 0-methyl derivatives. The infrared spectrum of 3- (p-methoxy-benzyl)quinoxalin-2-one (77) in methylene chloride shows bands at 3375 and 1565 cm" which are absent in the spectrum of the deuterated... 

The cationic species 4 thus formed reacts with water to give the iminol 5, which tautomerizes to a more stable amide tautomer, the N-substituted carboxylic amide 2. Those steps correspond to the formation of amides by the Schmidt reaction. A side reaction can give rise to the formation of nitriles. 

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