Primary enamines

Vinylamine (R = R = R3 = H) is the simplest primary enamine. It was prepared by gas-phase pyrolysis of ethylamine and characterized by its microwave spectrum which led to a crude determination of its molecular geometry . The interesting question refers to the extent of planarity or tetrahedral geometry of the amino group and this is discussed in the section on calculations of molecular structures. 

Stable primary enamines have been observed in the case of a- or j8-substitution of enamines by carbonyl or ester groups. The reduction of ethyl 3-methyl-2-nitro-2-butenoate (24) with aluminium amalgam afforded ethyl 2-amino-3-methyl-2-butenoate (25), the enamine form, whereas the treatment of ethyl 3-methyl-2-oxobutanoate (26) with triphenylphosphinimine yielded ethyl 2-imino-3-mcthylbutanoatc (27), the imino form, both of which were characterized by their IR and NMR spectra. These two isomers, 

25 and 27, did not tautomerize but they dimerized to 3,6-diisopropylidene-2,5-dioxopi-perazine (28) (equation 2). 

In the case of primary (and secondary ) )S-keto enamines, the enamino keto form 30a or 31a is stabilized by its push-pull conjugated mesomeric form 30b or 31b and by an intramolecular hydrogen bridge which dominates over the tautomeric imino enol form 30c or 31c (equation 3). Similar results are reported for jff-thioketone enamines .  

The primary enamino keto form 30a,b was separated from the more polar form 30c by continuous extraction with petroleum ether at — 25°C and evaporation of the solvent.  

3-aminoacroleins58 1 f vinylogous P-enaminoketones44 J amides p-enamino esters59 = vinylogous urethanes P-enamino amides = vinylogous ureas 

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This is the most common method for the preparation of enamines and usually takes place when an aldehyde or ketone containing an a hydrogen is treated with a secondary amine. The water is usually removed azeotropically or with a drying agent, but molecular sieves can also be used. Stable primary enamines have also been prepared.Enamino-ketones have been prepared from diketones and secondary amines using microwave irradiation on silica gel. ° Secondary amine perchlorates react with aldehydes and ketones to give iminium salts (2, p. 1178). Tertiary amines can only give salts (12). 

Tertiary enamines are the most stable ones and are the main subject of this chapter. Secondary and primary enamines tend to revert to the tautomeric imino form [4] (Eq. 3). 

The nitro group is remarkably versatile and solves otherwise difficult problems. The table is meant to help you see which synthons can be represented by nitro-compounds. Note particularly that the charged synthons all have unnatural polarity and the primary enamine in the Diels-Alder entry could not be made without protection of the amine. 

When there are two different heteroatoms in a five-membered aromatic ring, questions of regio-selectivity often arise. The unsymmetrical thiazole 27 might be disconnected at the imine to give the unstable primary enamine 28 and then at the thiolester to give an acylating agent and the undoubtedly very unstable 30. Note that 30 must have SH and NH2 on the same side of the alkene for cyclisation to be possible. We want to find a better way. 

In addition to aldehydes and ketones, a variety of other functional groups can be used as electrophiles in Reformatsky-type reactions.1-3 Among them, nitriles play a prominent role since they lead to p-oxoesters after hydrolytic work-up (the primary enamines initially formed can only be isolated when stabilized by extended conjugation or by conformational means, cf. Table 14.1, entry 4). 

The conjugated primary enamines 95 exhibit planar frameworks with alternating C=C double and C-C single bonds between their C(sp2) atoms. Conjugation extends through the C(NH2) center to the attached aryl ring systems which generally are oriented close to coplanar with the... 

Calculations of the simple primary enamine, vinylamine, have shown it to be non-planar36-39. This conclusion has been extended to tertiary enamines as well, based on the shape of bands in the photoelectron spectra40, on quantum-chemical calculations41-43 and on X-ray diffraction studies of crystalline enamines44-47 (cf Chapter 1). 

As noted above, ionization of cycloalkylamines provides facile access to ionized enamines in the gas phase. This is especially valuable in the case of primary enamines which are unstable as neutrals. 

Ionized primary enamines of low energy may also be reaction intermediates in the loss of ammonia. Scheme 34 shows a mechanism proposed for the extensive loss of ammonia from low-energy ionized 3-amino steroids. Enamine 63 may lose ammonia after two successive 1,4 H-transfers. The participation of the H at C(5) has been established by D-labelling42. Only higher energy ions lead to m/z 82 fragment ions through the ionized dienamine 64,... 

This cycloreversion reaction has been utilized to generate 34 and study its reactions with olefins in a FTICR spectrometer43. 34 has been found to react with various olefins essentially along two competing channels H atom abstraction leading to the immonium ion m/z 44 (Scheme 36) and regioselective cycloaddition-cycloreversion. The latter reaction opens up a new possible access to ionized primary enamines in the gas phase. 

Primary enamines 115 have been obtained by flash thermolysis of adducts 116 at 600 °C in vacuo. A retro-Diels-Alder reaction occurs to give vinylamine (R = R1 = R2 = H). These primary enamines have been identified by their spectroscopic properties at — 80 °C. At temperatures > 80 °C isomerization to the imine occurs as well as self-condensation to various nitrogen heterocycles or acyclic azadienes. 

Primary enamines are also postulated as intermediates in the conversion of vinyl azides into aldehydes or ketones505 (equation 30). 

Ellenberger and coworkers9,10 also estimated the basicity of some primary enamines by using the theoretically evaluated isomerization energy of the imine-enamine (4 3) reaction. Consequently, their reported basicities for primary enamines are less accurate than those obtained directly by them from equation 5, as usual for tertiary enamines. 

Let us consider vinylamine, a model for primary enamines. Figure 1 shows the linear relationship between AG° and IPV for saturated primary amines. The value for vinylamine clearly deviates from such a relationship, so this compound cannot be a nitrogen base. 

The 1,2,3-triazole 168 is the product of the slow reaction (70°C, 7 days) of phenyl azide with the primary enamine ethyl 5-amino-2,3-dihydrofuran-4-carboxylate (165). The authors propose that the initial cycloadduct 166 is transformed into the betaine 167, which cyclizes to the triazole as shown in equation 7595. 

The 1,4-dihydropyridine 271 is produced from the primary enamine ethyl / -aminocro-tonate and the perchlorate 270 (equation 112)137. 

Lithium aluminium hydride reduces tosylacetonitrile to the primary enamine / -(/ -toluenesulphonyl)vinylamine 274. Treatment of the latter with sodium hydride in THF at — 60°C furnishes the stabilized a-azaallyl anion 275, which is converted into the dihydropyridine 276 by reaction with benzylideneacetophenone (equation 114)140. 

Formamide converts the primary enamine 359 into 4-oxo-4,5,6,7-tetrahydro-3//-thiopyrano[2,3-d]pyrimidine 360 (equation 146)178. 

The primary enamine 126 (Ar = p-MeC6H4) (see equation 54) cyclizes thermally to the 4-aza-25-phosphinine 388, while potassium hydride converts it into the azapho-sphininone 389 (equation 160)75. 

Treatment of the primary enamine 394 (Ar = p-MeC6H4) with ethyl azidoformate results in the evolution of nitrogen and the formation of compound 395 the latter is converted into the 2-oxo-l,3,4/l5-diazaphosphinine 396 on heating at 150°C (equation 162)191. 

The primary enamine 359 reacts with triphenylphosphorus dichloride to yield compound 402, which is converted into the eight-membered sulphur heterocycle 403 by the action of methyl propiolate (equation 166)195. 

Hassner and Belinka118 generated primary enamines in situ by reaction of vinyl azides 67 with alkyl lithium derivatives and converted them to ketones (equation 45). 

Generation of the double bond of enamines is possible via a rDA reaction. Ethylenamine and its methyl derivatives have been prepared by FVP of the corresponding anthracene adducts (equation 24). Identification of the primary enamines in a pure state has been accomplished at -80 °C, while the less... 

New phosphono containing pyrimidine analogues, diazaphosphinine oxides (408), were obtained by cyclization of metalated primary enamine phospho-nates with nitriles (Figure 72). ... 

The cascade of reactions in hot nitrobenzene starts with a [3,3]-sigmatropic rearrangement thr unusual in that it forms an allene but is otherwise straightforward. To get to the next intermeci the stable conjugated primary enamine, we must enolize and go back to the ketone again but r the double bond into conjugation. 

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