Reaction imine-enamine tautomerism

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. 

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. 

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 reaction with 1-azabutadiene is also unfavorable for other reasons. To begin with, the 4 + 2 cyclization is inherently less exothermic than with 2-azabutadiene (see Exercise 20, p. 123). Furthermore, the enamine product will rapidly undergo side-reactions with adventitious electrophiles. An imine-enamine tautomerism which transforms R-N=CH-CH=CH-CH3 into RNH-CH=CH-CH=CH2 also contributes to lowering the yield. Finally, electron-poor dienophiles may undergo a competing reaction with the nitrogen lone pair. 

A reaction mechanism involving imine-enamine tautomerism has been proposed. A similar fluorination reaction has been observed for enamines (see Section 1.1.8.8.). 

Nevertheless, chemical reactions between imines and electrophilic reagents have revealed that imine-enamine tautomerization exists and that the enamine tautomers are the reactive species which undergo the reactions . For example, imines 12 prepared from aliphatic amines and a variety of ketones react with aryl azides to afford triazolines 14 in good yields, On heating or in the presence of catalytic amounts of an acid, triazolines 14 are converted to triazoles 15 in a process which may proceed via rearrangement and a deamination pathway (equation 4). Formation of 14 demonstrates clearly the existence of imine-enamine tautomerism during the reaction ... 

Figure 14 Structure and reaction mechanism of oxygen-dependent PPO. (a) Crystai structure of tobacco PPO in compiex with the cofactor FAD and a phenyi-pyrazol inhibitor. Each subunit of the dimeric protein consists of three domains, a membrane- (biue), an FAD- (red), and a substrate-binding (green) domain, (b) Proposed reaction mechanism for oxygen-dependent PPO. Ali hydride abstractions occur from C20 after imine-enamine tautomerizations. M = methyi, P = propionate.

Regioselective aza-annulation reactions have been achieved through the use of aryl substituted keto enamine substrates. Aryl substitution at the a-position of the enamine provides for regioselective imine-enamine tautomerization at the non aryl (i carbon. Early studies in this area compared the utility of pyrrolidine enamine versus benzyl imine derivatives of a-tetralone.8 In the absence of solvent, aza-annulation of 75 with acrylamide led to the formation of 76, but use of imine derivative 77 resulted in significantly higher yield of 76 (eq. 19).8 Similar reactions were observed between an aryl ethyl ketone and acrylamide (72% yield, dioxane, 70 °C) or acrylonitrile when catalyzed by AICI3 at 25 °C.33... 

Stereoregularity of the acrylic precursor has been shown by Peebles and Snow to be of no importance to the stabilization reaction [225] and one explanation given by Peebles [225] is a rapid imine-enamine tautomerization of the final cyclized unit causing racemization or scrambling of any chiral centers ... 

The E-isomer is generally more stable than the Z-isomer due to diminished steric hindrance, so it is assumed that the E-isomer is the major product (shown for 83). Water, a reaction by-product, may be removed to give a better yield of product and azeotropic distillation is used as well as molecular sieves (see Section 18.6.3). Enamines are structurally related to an end (HO—C=C) in that the heteroatom is directly attached to the alkene unit. Enamines are often isolable compounds, whereas enols tautomerize spontaneously to the carbonyl form. Note that when imine 76 is formed from iminium salt 80, there is no enamine product. In fact, the C-H in 80 is much less acidic that the N-H unit, so the product is the imine rather than the enamine. It is noted that there is an equilibrium between an imine and an enamine, known as imine-enamine tautomerism, but it will be ignored in this book. Many different secondary amines can be used in this reaction, including cyclic amines (see Chapter 26, Section 26.4.1) such as pyrrolidine (90), piperidine (91), and morpholine (92). It is important to note that it is generally easier to form an enamine from a ketone than from an aldehyde. 

The degradation of polyacrylonitrile deuteriated in the alpha position has been followed by Fourier transform i.r. spectroscopy. The results are consistent with imine-enamine tautomerism followed by oxidation to give pyridone structures. A variety of thermo-analytical techniques has been employed to study thermal and thermo-oxidative reactions and it is concluded from these that a carboxylate moiety is responsible for initiating cyclization in an oxidizing atmosphere. The role of oxygen is said to be three-fold, creation of the carboxylate initiator sites, dehydrogenation, and crosslinking. 

In 2006, Janecki et al [67] reported that when 2-diethoxyphosphoryl-4-oxoaUcanoates 137 are treated with primary amines, such as benzylamine and hexylamine, the formation of y-alkylidene-a-diethoxyphosphoryl-y-lactams 140 as the only products is observed (Scheme 4.37). 2-Diethoxyphosphoryl-4-aminoalkanoates 139 necessary for the cyclization reaction were formed from the initially formed imines 138 via imine-enamine tautomerization. Interestingly, the reaction sequence proceeded in a highly stereoselective manner as E-configured products (EfZ >95 5) predominated in the reaction mixtures. Subsequent HWE olefination of formaldehyde with phosphonates 140 yielded y-alkylidene-a-methylene-y-Iactams 141 in moderate to good yields with unchanged E/Z ratio with respect to the starting phosphonates 140. 

In this procedure, a hydrazone of an enolizable aldehyde or ketone is heated in strong acid, causing ring closure with simultaneous expulsion of ammonia to furnish the indole nucleus. [Hints The mechanism of the reaction proceeds in three stages (1) an imine-enamine tautomerization (recall... 

Some other reactions of the harmala alkaloids are simply consequences of imine enamine tautomerism but are nevertheless important for an understanding of the chemistry of the more complex indole alkaloids (see p. 39). 

In 2006, Hoffmann et al. described an efficient reductive amination of racemic aldehydes via dynamic kinetic resolution (Scheme 2.10). In the presence of 5mol% Brpnsted acid 5b, a-branched aldehydes 36 condensed with amines to form two imine enantiomers XI and X3 with different reaction rates in a transfer hydrogenation reaction, which then underwent a fast racemization via an imine-enamine tautomerization and resulted in enantioenriched P-branched chiral amine products 38 [17]. 

Undoubtedly, the main and the most general reason of complicated character of the reactions between 1,3-diketone dioximes and acetylene is the imine-enamine tautomerism (Scheme 1.83). 

The addition of ketens or keten precursors to cyclic imines to form /3-lactams has been known for some time and has been reviewed in two monographs. Using this method, Bose and co-workers were able to synthesize epi-penicillins in very few steps. The addition is successful with thioimidates " " and dithioimidates such as (146), from which (147) can be obtained. However, when imine-enamine tautomerism is possible [e.g. (148)], the reaction fails and the acylenamine (149) is formed in... 

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