Enamines tautomerization

Phenylmercury derivatives of 3-aminomethylene-l-methyloxindols have also been investigated (79KGS65). For studies of the effect of substituents on the electronic structure of silver and potassium salts of 3-(aryl)imi-nooxindole see 76MI2. The keto-enol and imino-enamine tautomerism of compounds of type 127 (with 128 and 129) has been investigated (85KGS921). 

L-idose 293, 311 ff. imine formation 57 imine-enamine tautomerization 467 iminium-RhH jt complex 351 f. imipenem 348 indoline ligands 681, 684 indolizomycin 47 Iff. -.retrosynthetic analysis 472ff. 

In marked contrast to the other hetero atom multiple bond functions cited in this section the >C=N- imine bond was not found to undergo hydrometalation. Imines with neighboring C-H bonds as in PhCH=NMe do react with 1 via imine/enamine tautomerism, but not by hydrozirconation [197]. 

Reactions of Halogenation and Nitrosation Nitrones with protons in the a-alkyl group can occur in tautomeric nitrone-hydroxylamine equilibrium (Scheme 2.117) similar to keto-enol and imine-enamine tautomerisms. 

The aminomethylenemalonates (1 and 2) may exist in imine or enamine tautomeric forms of R1 or R2 is a hydrogen atom. In some early papers, the imine tautomer (see below) was given for the structure of the products, usually without any explanation or evidence (e.g., 1885CB319 37JCS867 49JIC171 88KGS931). 

In the case of class-II inhibitors, the acyl-enzyme undergoes either normal deacylation (Fig. 5.3, Pathway c) or a chemical re-arrangement in which the enamine tautomerizes to an imine, generating an acyl-enzyme with a A -pyrroline structure (Fig. 5.3, Pathway b). This second acyl-enzyme intermediate hydrolyzes at a much slower rate, and the decreased tum°ver cacis t0 transient inhibition of the enzyme [22] [50]. 

We shall consider the sequence as firstly imine formation (an abbreviated form of this mechanism is shown), followed by imine-enamine tautomerism. This provides a nucleophilic centre and allows a subsequent aldol-type reaction with enamine plus ketone. The pyrrole ring is produced by proton loss and a dehydration. 

The solid-state interaction of enamines (428, 333a) with trans-l,2-diben-zoylethene (87) provides quantitative yields of the pyrrole derivatives 445 or 446 [140]. These remarkable 5-cascades consist of initial vinylogous Michael addition, enol/keto tautomerism, imine/enamine tautomerism, cyclization, and elimination, all within the crystal without melting. A waste-free extraordinary atom economy is achieved that cannot nearly be obtained in solution. The milling times are unusually long here (3 h) but it s certainly worth the effort... 

List later reported the asymmetric reductive amination of a wide spectrum of aromatic and aliphatic a-branched aldehydes via dynamic kinetic resolution (Scheme 5.27) [49]. The initial imine condensation product is believed to undergo fast racemization in the presence of the acid catalyst Ih through an imine/enamine tautomerization pathway. Preferential reductive amination of one of the imine enantiomers furnishes the optically pure P-branched amine. 

Pyrido[2,3-, pyridazine derivatives 48 have been synthesized by refluxing equimolar amounts of an appropriate 5-benzylidene-2,2-dimethyl-l,3-dioxane-4,6-dione 47 with 5-amino-6-phenylpyridazin-3(2/7)-one 46 in methanol or a methanol acetic acid mixture. The electron-poor carbon atom of the polarized carbon-carbon double bond of 47 is the electrophile attacking C-4 of the 5-aminopyridazinone 46. Imino-enamine tautomerization of the intermediate is followed by ring closure and subsequent loss of acetone and carbon dioxide affording the reaction products 48 as stable crystalline solids in 70-90% yield (Scheme 9) <2000T2473>. 

The acetic anhydride-induced cyclodehydration of the symmetrical diamide 411, derived from the tetrahydro-benzothiophene / -amino ester 410 and diethyl malonate, afforded the thieno[2,3-r7 [h3]oxazine derivative 413 rather than the expected bis-oxazine 412 (Scheme 78). The reaction probably takes place through sequential cyclizations, in which the pyridine ring of 413 is produced by condensation of the exocyclic double bond of the enamine tautomeric form of the 1,3-oxazine moiety and the mixed anhydride formed by the carboxylic group and acetic anhydride <2003PS245>. 

A reaction that is related to that of transketolase but is likely to function via acetyl-TDP is phosphoketolase, whose action is required in the energy metabolism of some bacteria (Eq. 14-23). A product of phosphoketolase is acetyl phosphate, whose cleavage can be coupled to synthesis of ATP. Phosphoketolase presumably catalyzes an a cleavage to the thiamin-containing enamine shown in Fig. 14-3. A possible mechanism of formation of acetyl phosphate is elimination of HzO from this enamine, tautomerization to 2-acetylthiamin, and reaction of the latter with inorganic phosphate. 

Scheme 5. Ring-chain and iminium-enamine tautomerism for the interconversion of per-hydropyrido[2,l-b][l,3]oxazines. a and /3 refer to the down vs. up orientation, respectively, of the alkyl substituents on C-2 and C-9 and of the hydrogen atom on C-9a.

Although azides cannot undergo addition to imines (Schiff bases),16,214 when the possibility of imine-enamine tautomerism exists, reaction occurs with the enamine to yield 5-aminotriazolines.35,43,81,180,208,214,223-226 In fact, Alder s N-4 compounds were obtained as shown in Scheme 49. 

The infrared spectrum has been employed mainly to establish the presence22 or absence23 of the NH function in the A3- and A4-triazolines in 10 the NH absorption appears at 3300 cm 1.22 Absence of imine-enamine tautomerization in 7 is also established by IR.6... 

The A-acylimine-enamide tautomerism of methyl 2-acetamidoacrylate has been studied641 by means of ab initio calculations. A 13C NMR investigation has been undertaken to study the tautomerism between the hydrazone imine and diazenylen-amine forms of 3-(arylhydrazono)methyl-2-oxo-l,2-dihydroquinoxalines,642 and the effects of temperature and side-chain on the imine-enamine tautomerism in quinoxalinone and pyridopyrazinone systems have been studied.643 A detailed... 

The imine-enamine tautomerism of 9-aminotetrahydro-4//-pyrido[l,2-a]pyrimidin-4-ones 32 (R = NR3Ph, R3 = H, Me) were studied by H and... 

A high density of electrons associated with atoms C(3) and C(5) of 1,4-dihydropyridines and 1,4-dihydropyrimidines is also observed when these heterocycles undergo electrophilic substitutions such as Friedel-Crafts [315, 316, 317, 318, 319, 320] and Vilsmeier [297, 321] reactions (Scheme 3.99). In [315] it was shown that treatment of dihydropyridines 371 with aroyl or acyl chlorides 372 in the presence of SnCl4 leads to acylation of the heterocycle at position 3 (compounds 373). Dihydropyridines 374 and dihydroazolopyrimidines 376 undergo Vilsmeier reaction with the formation of the corresponding derivatives 375 and 377. It is interesting that imine heterocycle 376 after Vilsmeier reaction exists in the enamine tautomeric form. The tautomerism of dihydroazines and factors influencing it will be discussed in detail in Sect. 3.8. 

The influence of steric factors is more significant for dihydroazolopyrimi-dines 430 fused with a hydrogenated carbocycle [156] (Scheme 3.141). Regardless of the nature of the azole and carbocycle moieties, these compounds usually exist in the enamine tautomeric form. 

The problem of tautomeric equilibriums in annelated 1,5-diazepines was studied in [68] by means of NMR spectroscopy, X-ray analysis and quantum-chemical calculations. It was shown that the electron-withdrawing rings (e.g., pyrimidine moiety) fused with the diazepine cycle increase the stability of the antiaromatic enamine tautomeric forms A and C, while in the case of benzodiazepine, a diimine tautomer B was found to be the most stable. Ab initio quantum-chemical calculations and NMR spectroscopic data showed that solvation of seven-membered heterocycles with polar solvents contributes considerably to the stabilization of the enamine forms A and C. This assumption was also proven by X-ray analysis, which showed that in the solid state these diazepines exist in the diimine form B. 

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