Imine formation elimination-addition

Imine formation and enamine formation appear different because one leads to a product with a C=N bond and the other leads to a product with a C=C bond. Actually, though, the reactions are quite similar. Both are typical examples of nucleophilic addition reactions in which water is eliminated from the initially formed tetrahedral intermediate and a new C=Nu bond is formed. 

The synthesis of aziridines through reactions between nitrenes or nitrenoids and alkenes involves the simultaneous (though often asynchronous vide supra) formation of two new C-N bonds. The most obvious other alternative synthetic analysis would be simultaneous formation of one C-N bond and one C-C bond (Scheme 4.26). Thus, reactions between carbenes or carbene equivalents and imines comprise an increasingly useful method for aziridination. In addition to carbenes and carbenoids, ylides have also been used to effect aziridinations of imines in all classes of this reaction type the mechanism frequently involves a stepwise, addition-elimination process, rather than a synchronous bond-forming event. 

Common reactions of the ylide include (i) [2,3]-sigmatropic rearrangement of allylic, propargylic, and allenic ylides (ii) [l,2]-shift (Stevens rearrangement) (iii) 1,3-dipolar cycloaddition of the ylide generated from carbonyl compounds or imines with dipolarophiles, usually G=G or C=C bonds and (iv) nucleophilic addition/elimination, leading to the formation of epoxides or cyclopropanes (Figure 2). 

Notice that an acid catalyst is normally added for imine formation. Without an acid catalyst, the reaction is veiy slow, though in some cases it may still take place (oximes, for example, will form without acid catalysis, but form much faster with it). It s important to notice that acid is not needed for the addition step in the mechanism (indeed, protonation of the amine means that this step is very slow in strong acid), but is needed for the elimination of water later on in the reaction. Imine formation is in fact fastest at about pH 4-6 at lower pH, too much amine is protonated and the rate of the first step is slow above this pH the proton concentration is too low to allow protonation of the OH leaving group in the dehydration step, Imine formation is like a biological reaction it is fastest near neutrality. 

The mechanism of imine formation (Mechanism 21.5) can be divided into two distinct parts nucleophilic addition of the 1° amine, followed by elimination of HgO. Each step involves a reversible equilibrium, so that the reaction is driven to completion by removing HgO. 

Imine formation proceeds by nucleophilic addition-elimination of NH3 to the ketone carbonyl group, with loss of water. Imines, like ketones, are polarised by the electronegativity difference between carbon and nitrogen. Nucleophilic addition of cyanide occurs to give an amino nitrile intermediate. 

Briefly, the mechanism for formation of an enamine is very similar to that for the formation of an imine. In the first step, nucleophilic addition of the secondary amine to the carbonyl carbon of the aldehyde or ketone followed by proton transfer from nitrogen to oxygen gives a tetrahedral carbonyl addition compound. Acid-catalyzed dehydration gives the enamine. At this stage, enamine formation differs from imine formation. The nitrogen has no proton to lose. Instead, a proton is lost from the a-carbon of the ketone or aldehyde portion of fhe molecule in an elimination reaction. 

Many addition-elimination reactions at carbonyl centers involve a nucleophilic attack on the carbonyl carbon, followed by an elimination that restores the double bond. We first explore addition followed by 1,2-elimination, one of many types of reactions referred to as condensations. Strictly speaking, a condensation occurs when two large molecules combine to create a more complex molecule with the loss of a small molecule, such as water or an alcohol. Therefore, a condensation is a form of substitution. We will also examine condensation reactions that form polymers (see Chapter 13). One of the more complex condensations is the formation of an imine or enamine from a carbonyl and an amine. In both of these cases an oxygen is replaced by a nitrogen with loss of water (Eq 10.105 and 10.106). 

The reactions of OFCP with methylamine and ethylamine include both the addition-elimination reactions at the double bond and the simultaneous formation of products 12 with the imine fiagmoits (100 % yield for Alk=Me and 72 % for Alk=Et) [38], The formation of azochromophores 13 with the perfluorocyclopentene bridge, including the reaction of substance 4 with thiols as the first stage, was described in [39],... 

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