Equilibrium imine-enamine

Certain geminal difluoro groups arc easily aminolyzed yielding imines or enamines.3,20-24 An imine-enamine equilibrium is generally observed,13,25 - 28 which is dependent on the substrate and the amine used. Nevertheless, /i-imino carboxylic esters are predominantly obtained when a-hydrylperfluoro esters (e. g., 4) are reacted with primary amines, while reaction with secondary amines leads to the respective enamines.29,30... 

One solution to the imine/enamine equilibrium is to load the nitrogen atom with a removable acyl group. Popular choices are urethanes and sulfonamides. If the nitrogen atom is unsubstituted 32, the imine 33 is favoured by conjugation but if the nitrogen is substituted 31, it is forced to give the enamine 29. 

Selective deuteriation of the pyrrolidine ring of conanine has been studied. A rapid imine-enamine equilibrium following Bredt s rule permitted the preparation of [17a- H]conanine (7) and [21,21,21- H3]conanine (8) by selective deuteriation. The 5a,20(N)-conene (9a), with deuteriomethanol in alkaline medium. 

The reaction starts with the formation of the usual imine/enamine equilibrium but what looks like an Sn2 displacement of SH by CN turns out to be an elimination followed by a conjugate addition. Any attempt at an Sn2 displacement would simply remove the proton from the SH group. Notice that the pyridoxal is regenerated. 

The mechanism begins with the reaction at C(l) to form a phenylhydrazone (p. 793), which consumes the first equivalent of phenylhydrazine. This hydrazone is an imine and imines are in equilibrium with enamines (p. 796), just as ketones are in equilibrium with enols.The imine-enamine equilibrium is shown in Figure 22.32. 

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 UV spectra of 9-(phenylamino)tetrahydro-4f/-pyrido[ 1,2-a] pyrimidin-4-ones 23 indicated the presence of an imine-enamine type of tautomerism in solution. A carboxyl or ester group in position 3 (R1 = COOR3 R3 = H, Et) and a methyl group in position 6 (R = Me) shifted the equilibrium toward the enamine form in a polar solvent [85JCS(P1) 1015]. For the imine tautomer, UV maxima at 235-250 nm and 280-300 nm and for the enamine absorbances at 260-265 nm and 355— 365 nm are characteristic. 

Spectroscopic studies of imine-enamine tautomerism have shown that the equilibrium is almost completely in favour of the imine form for simple aldehydes and ketones372-374. Nevertheless, some secondary enamines are sufficiently stable to exist in detectable amounts in equilibrium with the corresponding imines for example, the f-butylamine imine of cyclohexanone shows signals due to the secondary enamine tautomer in the NMR spectrum (<5=CH 4.6)375. Studies of the imine-enamine equilibria have shown, as expected, that the enamine form is stabilized by methyl or aryl substituents at the -position (Scheme 189). 

Although this methodology is widely applicable for the preparation of many 1,1-enediamines, 2-(aroylmethylene)benzimidazolines (29) cannot be obtained from the reaction of benzoyl-substituted ketene dithioacetals 30 and o-phenylenediamine. Instead of 29, 3H- 1,5-benzodiazepines 31 are isolated from the reaction64. Similar results have been reported for the reaction of 30 and other primary aromatic diamines70,71. A recent study64 has revealed that an enamine-imine tautomeric equilibrium is involved in the reaction process (Scheme 2). This equilibrium between 33A and 33B is affected by the... 

The ketimine (13a), prepared from desoxybenzoin and aniline, is also subject to a solvent-dependent tautomerism called imine/enamine tautomerism. The enamine content of a solution of (13a) increases in the order tetrachloromethane (31 cmol/mol at 35 °C), [Dsjpyridine (47.5 cmol/mol at 55 °C), and [Dejdimethyl sulfoxide (67 cmol/mol at 55 °C) [69], Hydrogen-bond acceptor solvents favour the enamine form (13b) due to hydrogen-bonding, whereas in less polar and apolar solvents the equilibrium is shifted towards the imine form / 13a) [69]. 

Horvath et reported that the tricyclic formyl derivatives 390 n = 0-2) exhibit triple tautomerism between forms 451 and 453. The imine-enamine-enol tautomerism depends greatly on the ring size ( ). A significant solvent dependence was observed only for the pyirolo[2,l-i ]-quinazolinones 390 n = 0), which in ethanolic solution exist predominantly in the imino form (451), and in chloroform in the enol form (453). H-NMR spectroscopy showed that in chloroform the proportion of the imine tautomer 451 was about 5%. The fast equilibrium between the en-amine and enol forms 452 and 453 was shifted considerably toward the enamine tautomer 452 in the case of the pyrido[2,l-fi]quinazolinones 390 ( = 1). The azepino[2,1 -6]quinazoline ( = 2, R = 2-NO2) is a 2 3 mixture of the imine and the enamine tautomers 451 and 452. 

Tautomerization is the shift of an H from a carbon adjacent to a carbon-heteroatom double bond to the heteroatom itself (and the reverse). It is an acid- or base-catalyzed equilibrium. Two examples are the keto/enol pair (Z = oxygen) and the imine/enamine pair (Z = nitrogen). Base catalysis goes via the enolate anion. 

Extensive studies have shown that the enamine-imine tautomeric equilibrium of equation 1 shifts almost completely to the enamine side when an unsaturated electron-withdrawing group including nitrile nitro °, carbonyl, thiocarbonyP etc. ° is attached to the -carbon. Reviews related to these enamines which include enaminoni-triles 2, nitroenamines 3, enaminones 4 and the enaminothioketones 5, have appeared in the literature, ... 

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