Formation of imines

7 Nucleophilic addition of amine nucleophiles formation of imines and enamines 

Aldehydes and ketones react with primary amines (RNH2) to yield imines and react with secondary amines (R2NH) to form enamines. 

This reversible, acid-catalysed process involves the addition of a nucleophile, followed by elimination of water this is known as an addition-elimination or condensation reaction. (A condensation reaction involves the combination of two molecules to form one larger molecule, with the elimination of a small molecule, often water.) 

There are a number of related reactions, which employ similar nucleophiles. 

Like amines, imines are basic a substituted imine is also called a Schiff base. Imine formation is an example of a large class of reactions called condensations, reactions in which two (or more) organic compounds are joined, often with the loss of water or another small molecule. 

---

The formation of imines mkes place by a mechanism that is the reverse of the hydrolysis. Preparative proc ures often ensure completion of the reaction by removing water as it is formed by azeotropic distillation or by the use of an irreversible dehydrating agent. 

Carbinolamines are formed by nucleophilic addition of an amine to a carbonyl group and are intermediates in the formation of imines and enamines. 

Apparently, aminobutenyne A, the intermediate of the pyrrole synthesis, is fixed in an advantageous eonfiguration by eoordination to the Cu eation, whereas the absenee of eatalyst may result in the formation of imine B having an aetive methylene group whieh attaeks the aeetylene bond to form dihydropyridine C and then pyridine 2 (by dehydrogenation). 

Drivers for Performing Formation of Imines in Micro Reactors... 

Beneficial Micro Reactor Properties for Formation of Imines... 

Hydroamination of terminal alkynes with primary amines has been performed using organoactinides as catalysts [301, 302]. The organouranium complex Cp 2UMe catalyzes the regioselective formation of imines in fair to high yields (Eq. 4.82). 

Another route for the formation of imines is the treatment of secondary carboxamides with an excess of 1 [196],... 

Amines can react with various carbonyl compounds and their derivatives in aqueous media to give the corresponding imine derivatives. These reactions have been discussed in related chapters. The synthetically most useful reaction of this type is the formation of imines and imine derivatives from the condensation of amines with aldehydes and ketones. Water is an excellent solvent for such condensation reactions. For example, water was found to be an ideal solvent for a high-yield, fast preparation of easily hydrolyzable 2-pyrrolecarbaldimines.23 In the presence of Cu2+, the reaction afforded the corresponding Cu(II) chelates (Eq. 11.19). 

TiCl4 also effectively promotes formation of imines and enamines from carbonyl compounds (Scheme 31). The combination of imine formation using TiCl4 and reduction leads to reductive alkylation of an amine moiety.113,114... 

Similarly, imines can be formed by the condensation of ketones and suitable primary amines under microwave conditions (Scheme 6.148). Since the formation of imines is an equilibrium process, these transformations are best carried out under... 

Scheme 6.20 Clay-catalyzed formation of imines under solvent-free conditions.

Stable 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide reacts with 2- and 4-aminopyridines in their imino forms, if acids are present to promote the formation of imine, to give cycloadducts such as 168 (337). 

If the hydroformylation of olefins is conducted in the presence of aromatic hydrazines and Bronsted or Lewis acids indoles can be obtained directly in one pot [91-93,95]. Hydroformylation of the olefin gives an intermediate aldehyde, which is trapped immediately by the present aromatic hydrazine as an aromatic hydrazones similar to the formation of imines under hydroformylation conditions. Under acid mediation these aromatic hydrazones undergo a Fischer indolization, consisting of a [3,3]-sigmatropic rearrangement followed by a cyclization and elimination of ammonia (Scheme 38). 

Formation of imines (addition of amines to aldehydes or ketones)... 

The reductive amination reaction (Scheme 12.10) has two steps the formation of imine and the reduction of imine. The single bead FTIR results (Fig. 12.14) show the combined result of both steps. The aldehyde IR bands at 1682 and 2769 cm disappeared in the final product. However, this did not suggest that the... 

Scheme 6.104 Key intermediates of the proposed catalytic cycle for the 100-catalyzed Michael addition of a,a-disubstituted aldehydes to aliphatic and aromatic nitroalkenes Formation of imine (A) and F-enamine (B), double hydrogen-bonding activation of the nitroalkene and nucleophilic enamine attack (C), zwitterionic structure (D), product-forming proton transfer, and hydrolysis.

Also other reaction types have been dealt with in CHEC(1984) and CHEC-II(19%) like reduction to alcohols (e.g., sodium borohydride), Wolff Kishner reduction, nucleophilic addition via reaction with Grignard reagents or organo-lithium compounds, and formation of imine type functional groups (e.g., hydrazones). New examples are the reaction of... 

Few methods are available to determine enantiomeric purity of aldehydes by NMR spectroscopy of diastereomeric derivatives. The formation of imines. oxazolidines and more recently the advantageously C2-symmetrical imidazolidines with optically pure reagents can be utilized. 

A third early mechanism for enzymic processes involves the formation of imines between the amino group of a lysine residue on an enzyme and the carbonyl group of a substrate, followed by standard imine chemistry. The first example concerned the decarboxylation of acetoacetic acid (Hamilton and Westheimer, 1959). The mechanism was based on the non-enzymic physical organic chemistry of Kai Pedersen (Pedersen, 1934). He postulated that the catalysis by aniline of the decarboxylation of dimethylacetoacetic acid proceeds by a mechanism parallel to that shown in Scheme 7 for acetoacetic acid itself (Pedersen, 1938). 

Torisawa [17] developed an alternative oxidative amidation of aldehydes using palladium chloride (PdCl2)-xantphos complex as a catalyst. The use of hydrogen peroxide (H2O2)-urea complex as oxidant prevents the formation of imine from the carbinolamine intermediate and minimizes the level of benzoic acid side... 

As we have seen already, many enzymatic reactions depend upon formation of imines, which are commonly called Schiff bases. The two-step formation of Schiff bases consists of addition of an amino group to a carbonyl group to form a carbinolamine followed by elimination of water (Eq. 13-4).26 One group of aldolases (Section D) have, at their active centers,... 

Trimethyl orthoformate has been used as a solvent by Campbell and co-workers for site-selective monoalkylation in SPPSi1 % Trimethyl orthoformate was previously shown to be a highly efficient dehydrating solvent for the formation of imines. 112 Thus, dividing the reductive alkylation step into two separate substeps of (1) imine formation followed by solvent removal and (2) reduction, resulted in on-resin monoalkylation of various amino acids and dipeptides (Scheme 26). 

The most important reaction of this type is the formation of imine bonds and Schiff bases. For example, salicylaldehyde and a variety of primary amines undergo reaction to yield the related imines, which can be used as ligands in the formation of metal complexes. However, it is often more desirable to prepare such metal complexes directly by reaction of the amine and the aldehyde in the presence of the metal ion, rather than preform the imine.113 As shown in Scheme 31, imine formation is a reversible process and isolation of the metal complex results from its stability, which in turn controls the equilibrium. It is possible, and quite likely, that prior coordination of the salicylaldehyde to the metal ion results in activation of the carbonyl carbon to amine nucleophilic attack. But it would be impossible for a precoordinated amine to act as a nucleophile and consequently no kinetic template effect could be involved. Numerous macrocyclic chelate systems have been prepared by means of imine bond formation (see Section 61.1.2.1). In mechanistic terms, the whole multistep process could occur without any geometrical influence on the part of the metal ion, which could merely act to stabilize the macrocycle in complex formation. On the other hand,... 

Formation of Imines or Enamines From a-Hydrylperfluoro Carboxylic Esters General Procedure 2 ... 

---