Amine carbonyl addition reactions

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... 

You saw a carbonyl addition reaction forming a polymer right at the beginning of the chapter—the polymerization of formaldehyde. If an amine is added to formaldehyde, condensation to form imines and imine salts occurs readily. These intermediates are themselves electrophilic so we have the basis for ionic polymerization—electrophilic and nucleophilic molecules present in the same mixture. Reaction with a second molecule of amine gives an aminal, the nitrogen equivalent of an acetal. 

The non-equivalence of enantiomers through the spontaneous breaking of mirror-symmetry in nature is amplified by asymmetric autocatalytic reaction [34], e.g. Frank s spontaneous asymmetric synthesis [35, 36] (Fig. 7-8). Alberts and Wyn-berg have reported in enantioselective autoinduction that chiral lithium alkoxide products may be involved in the reaction to increase the enantioselectivity (Eq. (7.9)) [37]. The product % ee however does not exceed the level of catalyst % ee. In asymmetric hydrocyanation catalyzed by cyclic dipeptides, the (Si-cyanohydrin product complexes with the cyclic peptide to increase the enantioselectivity in the (S)-cyanohydrin product, the reaction going up to 95.8% ee (Eq. (7.10)) [38]. In the presence of achiral amine, (/ )-l-phenylpropan-l-ol catalyzed carbonyl-addition reaction of diethylzinc has been reported to show lower % ee than that of the catalyst employed [39]. 

Amines (Lewis bases) react with carbonyl groups (Lewis acids) by carbonyl addition reactions. Indeed, a substantial fraction of organic chemistry is concerned with carbonyl addition reactions of which this is a typical example. What we wish to discuss here is both their interaction and also their reaction. What, exactly, happens when these two groups come together, and how do they interact or react ... 

The usual procedure is to simply heat a mixture of the starting materials. A common side-reaction is the polyalkylation it can be suppressed by employing an excess of amine. In addition carbonyl substrates with a-hydrogens may undergo competitive aldol reactions the corresponding reaction products may then undergo a subsequent Leuckart-Wallach reaction. 

Each of the following substances can be prepared by a nucleophilic addition reaction between an aldehyde or ketone and a nucleophile. Identify the reactants from which each was prepared. If the substance is an acetal, identify the carbonyl compound and the alcohol if it is an imine, identify the carbonyl compound and the amine and so forth. 

Imines and iminium ions are nitrogen analogs of carbonyl compounds and they undergo nucleophilic additions like those involved in aldol reactions. The reactivity order is C=NR < C=0 < [C=NR2]+ < [C=OH]+. Because iminium ions are more reactive than imines, the reactions are frequently run under mildly acidic conditions. Under some circumstances, the iminium ion can be the reactive species, even though it is a minor constituent in equilibrium with the amine, carbonyl compound, and unprotonated imine. 

FIGURE 2.27 More on additives. In a carbodiimide-mediated reaction between acid 1 and amine 2, addition of HOObt can lead to the side reaction of aminolysis at the carbonyl of the activating moiety of ester 3, generating addition product 4. Addition of HOBt to a mixed-anhydride reaction containing unconsumed chloroformate generates mixed carbonate 5, leading to production of urethane 6. 

The successful synthesis of 2-thienyl and substituted 2- and 3-thienyl-acetylenes in yields as high as 60-80% opened a wide variety of synthetic applications. Various addition reactions with carbonyl compounds or epoxides could be carried out with ease. Aliphatic as well as aromatic amine addition reactions, or condensation reactions with hydrazine or hydroxylamine could be easily performed. 

Secondary amines react with aldehydes and ketones via addition reactions, but instead of forming imines, produce compounds known as enamines. Initially, there is the same type of nucleophilic attack of the amine onto the carbonyl system, followed by acid-catalysed dehydration but, since the amine is secondary, the product of dehydration is an iminium... 

Reductive alkylation of ammonia should give primary amines, reductive alkylation of primary amines secondary amines, and reductive alkylation of secondary amines tertiary amines. In reality, secondary and even tertiary amines are almost always present to varying extents since the primary amines formed in the reaction of the carbonyl compounds with ammonia react with the carbonyl compounds to give secondary amines, and the secondary amines similarly afford tertiary amines according to Scheme 128. In addition, secondary amines may be formed, especially at higher temperatures, by additional reactions shown in Scheme 129. Depending on the ratios of the carbonyl compounds to ammonia or amines, different classes of amines predominate. 

Formation of C-C bonds remains the ultimate challenge to the synthetic chemist. The employment of new synthetic methods in complex target synthesis can be frustrated by a lack of functional group tolerance and substrate specificity. These problems can be somewhat alleviated within conjugate addition reactions by the use of secondary amine catalysts where a number of important and highly selective methods have been developed. Two principle classes of nucleophile have been shown to be effective in the iminium ion activated conjugate addition of carbon nucleophiles to a,P-unsaturated carbonyl systems aryl, heteroaromatic and vinyl... 

In 2007, Tron and Zhu reported the multicomponent synthesis of 5-iminoox-azolines (42) starting from a,a-disubstituted secondary isocyano amides (41), amines, and carbonyl components (see Fig. 15) [155]. The reaction presumably follows a similar mechanism as in the 2,4,5-trisubstituted oxazole MCR (described in Fig. 11) however, because of the absence of a-protons at the isocyano amide 41, the nonaromatized product is obtained. As in the 2,4,5-trisubstituted oxazole MCR, toluene was found to be the optimal solvent in combination with a weak Brpnsted acid. The reaction was studied for a range of aldehydes and secondary amines. In addition, a variety of functionalities such as acetate, free hydroxyl group, carbamate, and esters are tolerated. Clean conversions were observed for this MCR as indicated by NMR analysis of the crude products (isolated yield 50-68%). The... 

Xu et al reported using [bmim][OH] as a basic IL for the Aza-Michael addition reaction between various amines and a,(3-unsaturated carbonyl compounds and nitriles. The products were obtained in high yields and the IL could be recycled eight times without significant change in the product yields. 

Ionic liquids have been used for the selenium- or palladium-catalyzed carbonylation of primary amines to form carbamates or ureas.After completion of the carbonylation, addition of water induced the precipitation of desired products, which were isolated by fdtration and separated from the ionic liquid, containing the catalytic species. Then, the catalyst could be reused after removal of residual methanol and water by distillation. Although the conversion of the reaction slightly decreased after the second run, the catalytic activity was considerably improved (from 70% to 99 %) by the addition of a small amount of the fresh catalyst. " ... 

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