Enamines nitrogen analogue

There is a distinct relationship between keto-enol tautomerism and the iminium-enamine interconversion it can be seen from the above scheme that enamines are actually nitrogen analogues of enols. Their chemical properties reflect this relationship. It also leads us to another reason why enamine formation is a property of secondary amines, whereas primary amines give imines with aldehydes and ketones (see Section 7.7.1). Enamines from primary amines would undergo rapid conversion into the more stable imine tautomers (compare enol and keto tautomers) this isomerization cannot occur with enamines from secondary amines, and such enamines are, therefore, stable. 

The essential feature of enamines is that they are nitrogen analogues of enols and behave as enolate anions. They effectively mask a carbonyl function while activating the compound towards nucleophilic substitution. 

A milder alternative to direct alkylation of enolate ions is the formation and alkylation of an enamine derivative. An enamine (a vinyl amine) is the nitrogen analogue of an enol. The resonance picture of an enamine shows that it has some carbanion character. 

Enamines of primary amines, or even of ammonia, also exist, but only in equilibrium with an imine isomer. The interconversion between imine and enamine is the nitrogen analogue of enoliza-tion, which is discussed in detail in Chapter 21. 

Just as enamines are the nitrogen analogues of enols, aza-enolates are the nitrogen analogues of enolates. They are made by deprotonating enamines with strong base. You will see both enamines and aza-enolates in action in Chapters 26 and 27. 

Surprisingly, acyclic 1,1-enediamine analogues react with 194 to give products 196 with elimination of HN02. Oxidation of 196 leads to 2,3-diphenylmaleimides (197) (equation 81). The products were identified on the basis of spectral data and by comparison with authentic samples. The mechanism proposed starts with attack of the enamine nitrogen on the carbonyl moiety of 194. 

One specific enol equivalent that works very well for aldehydes is an enamine. Secondary amines such as Me2NH, Et2NH, pyrrolidine, piperidine, or morpholine 34 add cleanly to aldehydes to give enamines 36. These relatively stable nitrogen analogues of enols react well with reactive alkyl halides, such as a-carbonyl halides, and in Michael additions. They were considered in chapter 2 and only a few extra examples will be given here. 

Enamines are the nitrogen analogues of enols but their formation from imines is thermodynamically more favourable than enol formation from ketones (Table 1). The equilibrium constant for enol formation is ca. 10 compared with a value of 10 for enamine formation. However, at pH 7 half of the imine exists as the iminium ion and the proportion of enamine present is 10 -fold greater than the proportion of enolate anion. In general, this implies that loss of an electrophile from... 

Cyclic analogues of hydrazones [151], 2-pyrazolines, show both protonation and alkylation on N-1, as has already been discussed on page 326. The sp nitrogen (which distinguishes these systems from enamines) does not appear to play any direct part. 

The Stork s aza-annulation method with acrylamide180,181 has been used frequently for the synthesis of six-membered nitrogen-containing heterocycles. Recently, this reaction was applied to the synthesis of 315 and 316 from protected enamine 314 (equation 68)182. Compound 315 is a key intermediate in the synthesis of the alkaloid Huperzine A and its analogues. 

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