Enamine carbonyls structure

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. 

Since Stork et al. introduced as a new synthetic method the alkylation and acylation of carbonyl compounds via enamines, this class of compounds has been the subjeet of intensive studies 1-3). The exceptional physical and chemical behavior of the enamine structure can be ascribed to resonance by conjugation of the unshared pair of electrons of the nitrogen atom with the 77 electrons of the double bond ... 

Hydrolysis of an enamine yields a carbonyl compound and a secondary amine. Only a few rate constants are mentioned in the literature. The rate of hydrolysis of l-(jS-styryl)piperidine and l-(l-hexenyl)piperidine have been determined in 95% ethanol at 20°C 13). The values for the first-order rate constants are 4 x 10 sec and approximately 10 sec , respectively. Apart from steric effects the difference in rate may be interpreted in terms of resonance stabilization by the phenyl group on the vinyl amine structure, thus lowering the nucleophilic reactivity of the /3-carbon atom of that enamine. 

The close agreement of the three methods supports the contention that protonation at low temperatures first occurs at nitrogen and is followed by a proton shift to give the iminium salt (M). The rate of this rearrangement is dependent on temperature, the nature of the amine, and the nature of the carbonyl compound from which the enamine was made. Even with this complication the availability of iminium salts is not impaired since the protonation reaction is usually carried out at higher temperatures than —70°. Structurally complicated enamines such as trichlorovinyl amine can be readily protonated (17,18). 

A recent adaptation of the procedure employing perchlorate and fluoro-borate salts has been reported by Leonard and Paukstelis (J5). This report includes proof of structure by direct comparison to iminium salts prepared by protonation of enamines. The general reaction reported was that of a ketone or aldehyde with a secondary amine perchlorate to give iminium salts. A large structural variety of carbonyl compounds and several amine... 

The formation of enamines from carbonyl compounds and secondary amines usually entails as only questionable structural feature, the possible isomeric position of double bonds in the product. Molecular rearrangements have not presented synthetic limitations. A notable exception is the generation of o-aminophenols on distillation of enamines derived from 2-acylfurans 620,621). 

Coniine, molecular model of. 28 structure of, 294 Conjugate acid, 49 Conjugate base, 49 Conjugate carbonyl addition reaction, 725-729 amines and, 727 enamines and, 897-898 Gilman reagents and, 728-729 mechanism of, 725-726 Michael reactions and, 894-895 water and. 727 Conjugated diene, 482... 

The high barriers in compounds 31 and 32 may be attributed to the fact that in these compounds the two carbonyl groups are coplanar with the enamine moiety, whereas such a coplanar structure is impossible for the open-chain compounds. Based on this point of view, Kdlle and associates extended the work further and were able to isolate a series of compounds (33,34) in one crystalline atropisomeric form (73). 

The crystal structures of thiamin-dependent enzymes (see next section) as well as modeling102 103 suggest that lactylthiamin pyrophosphate has the conformation shown in Eq. 14-21. If so, it would be formed by the addition of the ylid to the carbonyl of pyruvate in accord with stereoelectronic principles, and the carboxylate group would also be in the correct orientation for elimination to form the enamine in Eq. 14-21, step b.82 83a A transient 380- to 440-nm absorption band arising during the action of pyruvate decarboxylase has been attributed to the enamine. 

Secondary amino compounds of the type R2N—H add to aldehyde and ketone carbonyl groups in an acid-catalyzed reaction in much the same way as do RNH2 compounds—with one important difference. The product contains the structural unit C=C—N rather than C—C—N and because there is a carbon-carbon double bond, such a substance is called an enamine (alkene + amine). An example is ... 

When the donor and the acceptor of the conjugate addition are carbonyl compounds, the amine catalyst may activate both reagents, forming the iminium and enamine intermediates, respectively. The major mechanistic path is dictated by the structure of the substrates and catalyst and, to a lesser extent, by the reaction conditions. 

The double bond is kept in the exocyclic position by conjugation with the carbonyl group (the free base absorbs at 3270 cm-1). The free base of l-(a-picolyl)-6,7-methylenedioxy-3,4-dihydroisoquinoline also possesses the stabilized enamine structure, whereas the imino structure is exhibited by the 1-methyl analog, as shown by comparison of the... 

The study of the enamine structure may be associated, to a certain degree, with the problem of the so-called pseudobases an instructive, but somewhat specialized, review of these compounds was contributed by the late Professor Beke 47 to the first volume of this series. The name pseudobases was given by Hantzsch,48 towards the end of the last century, to those a-aminocarbinols which undergo a structural change during salt formation and yield salts with the loss of one molecule of water. The liberation of pseudobases from their salts is accompanied by rehydration. This behavior has been observed with a,/3-unsaturated heterocyclic compounds and, to a certain degree, with aromatic heterocyclic pyridine derivatives. As formulated by Gadamer,49 the pseudobases represent a potential tautomeric system of three components, the quaternary hydroxide A, the carbinolamine B, and the open-chain amino-carbonyl derivative C, in which all three components exist in a mobile equilibrium ... 

Indole and alkyl-indoles (38) are protonated in position 3 by the action of strong mineral acids.198,197 The tendency of the enamine salts to assume the immonium structure is very general the salts of ethyl j3-aminoerotonate are derived from the imino form at the expense of the conjugation between the carbonyl group and the double bond.12,198... 

Dihydropyrans (330) have been found to be the first formed product in the reaction of a,/ -unsaturated carbonyl compounds 327 with enamines 328 and their stability is highly dependent on the enamine and heterodiene structures. The formation of these dihydropyrans could occur via a concerted [4 + 2] cycloaddition reaction or via a two-step process involving a zwitterionic immonium enolate intermediate 329 (equation 71). 

Enamines are important functionalities in general organic chemistry their structures being defined by a double bond with a vinyl amine. These structures are easily formed by the addition of amines to carbonyl compounds [70,71]. As shown in Scheme 6.41, the formation of enamines, when applied to sugars, can produce unsaturation at the 2,3 position [72]. In the example shown, a 2-deoxysugar derivative was condensed with pyrrolidine giving the illustrated enamine. 

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