Carbonyl compound and amination

Photoredox systems involving carbonyl compounds and amines are used in many applications. Carbonyl compounds employed include benzophenone and derivatives, a-diketones [e.g. benzil, cainphoroquinone (85),2W 291 9,10-phenanthrene quinone], and xanthone and coumarin derivatives. The amines are tertiary and must have a-hydrogens [e.g. N,A7-dimethylani 1 ine, Michler s ketone (86)]. The radicals formed are an a-aminoalkyl radical and a ketyl radical. 

Schiff base org chem RR C=NR" Any of a class of derivatives of the condensation of aldehydes or ketones with primary amines colorless crystals, weakly basic hydrolyzed by water and strong acids to form carbonyl compounds and amines used as chemical intermediates and perfume bases, in dyes and rubber accelerators, and in liquid crystals for electronics, shif, bas ... 

The combined reaction thus involves initial formation of the iminium ion from the carbonyl compound and amine at pH 6, and this intermediate is then reduced by the complex metal hydride to give the amine. This can also he a way of making methyl-suhstituted amines via intermediate imines with formaldehyde. 

Figure 1. Optically Active Carbonyl Compounds and Amines... 

Table I. Optically Active Carbonyl Compounds and Amines Prepared by Asymmetric Synthesis Using the SAMP/RAMP Hydrazone Method... 

In many cases, free imines are hydrolytically unstable. In general, it is difficult to form imines from carbonyl compounds and amines in aqueous solution. This is not always the case, and it is sometimes possible to form conjugated imines which are stabilised by delocalisation in aqueous conditions (Fig. 4-22). 

The interconversion of imines and the constituent carbonyl compounds and amines is a stepwise process in which the first stage is the formation of an intermediate aminoalco-hol or aminol (Fig. 4-26). 

On the other hand, rare-earth trifluoromethanesulfonates (rare earth triflate, RE(OTf)3) have been found to work efficiently as Lewis acids even in aqueous media or in the presence of amines [4], A catalytic amount of RE(OTf)3 enables several synthetically useful reactions, for example aldol, Michael, allylation, Mannich, Diels-Alder reactions, etc., to proceed. It has also been demonstrated that a small amount of RE(OTf)3 is enough to complete the reactions and that RE(OTf)3 can easily be recovered from the reaction mixture and can be reused. A key to accomplishing the catalytic processes was assumed to be the equilibrium between Lewis acids and Lewis bases, for example water, carbonyl compounds, and amines, etc. A similar equilibrium was expected between Lewis adds and aromatic ketones, and, thus, RE(OTf)3-catalyzed Friedel-Crafts acylation was investigated [5]. 

Like acetals, imines are unstable with respect to their parent carbonyl compound and amine, and must be formed by a method that allows removal of water from the reaction mixture. 

Imines are readily hydrolysed back to carbonyl compound and amine by aqueous acid—in fact,... 

The simplest synthesis for a heterocycle emerges when we remove the heteroatom and see what electrophile we need. We shall use pyrroles as examples. The nitrogen forms an enamine on each side of the ring and we know that enamines are made from carbonyl compounds and amines. 

Principally, the same ring closure reactions as for tetraazacycles (Section 14.11.5.3) can be applied for preparation of larger polyazamacrocycles however, mostly tosylamide and peptide-like syntheses are employed. In addition, metal template or cyclization reactions between carbonyl compounds and amines (and reduction of intermediate Schiff base) are often utilized. 

Problem 21.28 What carbonyl compound and amine are formed by the hydrolysis of each compound ... 

Preparation of imines and enamines from carbonyl compounds and amines can be achieved with a dehydrating agent under acid/base catalysis [563]. Basically, primary amines afford imines unless isomerization to an enamine is favored as a result of conjugation, etc (see Eq. 252), and secondary amines afford iminium salts or enamines. These transformations can be conducted efficiently with a catalytic or stoichiometric amount of a titanium salt such as TiCU or Ti(0-/-Pr)4. Equation (247) illustrates an advantageous feature of this method in the imination of a hindered ketone. f-Butyl propyl ketone resisted the formation of the imine even by some methods reported useful for sterically hindered ketones [564,565]. The TiCU-based method works well, however, for this compound, giving the desired imine in high yield within a relatively short reaction period [566]. Imine derivatives such as iV-sulfonylimines could be... 

A closely related method does not require conversion of enantiomers to diastereomers, but relies on the fact that (in principle, at least) enantiomers have different NMR spectra in a chiral solvent, or when mixed with a chiral molecule (in which case transient diastereomeric species may form). In such cases, the peaks may be separated enough to permit the proportions of enantiomers to be determined from their intensities.Another variation, which gives better results in many cases, is to use an achiral solvent but with the addition of a chiral lanthanide shift reagent such as fn5[3-trifluoroacetyl-(i-camphorato]europium(III). ° Lanthanide shift reagents have the property of spreading NMR peaks of compounds with which they can form coordination compounds, for example, alcohols, carbonyl compounds, and amines. Chiral lanthanide shift reagents shift the peaks of the two enantiomers of many such compounds to different extents. 

The examples outlined in this chapter show that carbohydrates are efficient stereodifferentiating auxiliaries, which offer possibilities for stereochemical discrimination in a wide variety of chemical reactions. Interesting chiral products are accessible, including chiral carbo- and heterocycles, a- and 3-amino acid derivatives, 3-lactams, branched carbonyl compounds and amines. Owing to the immense material published since the time of the earlier review articles on carbohydrates in asymmetric synthesis [9,10], the examples discussed in this chapter necessarily focused on the use of carbohydrates as auxiliaries covalently linked to and cleavable from the substrate. Given the scope of this chapter, a discussion of other interesting asymmetric reactions has not been permitted — for example, reactions in which carbohydrate-derived Lewis acids, such as cyclopentadienyl titanium carbohydrate complexes, exhibit stereocontrol in aldol reactions [180]. Similarly, processes in which in situ glycosylation induces reactivity and stereodifferentiation — for example, in Mannich reactions of imines [181] — have also been excluded from this discussion. 

Properties Usually colorless, crystalline solids, although some are dyes. Very weakly basic and hydrolyzed by water and strong acids to carbonyl compounds and amines. 

Schiff base. An imine, derived by chemical condensation of aldehydes or ketones with primary amines very weakly basic and hydrolyzed by water to form carbonyl compounds and amines. 

The Kabachnik Fields reaction, which involves the hydrophosphonylation of phos phites with imines generated in situ from carbonyl compounds and amines, is an attractive method for the preparation of a amino phosphonates. Optically active a amino phosphonic acids and their phosphonate esters are an attractive class of compounds due to their potent biological activities as nonproteinogenic analogues of a amino acids. Therefore, considerable attention has been given to their enantio selective synthesis by hydrophosphonylation of preformed imines, using either metal based catalysts or organocatalysis [107]. 

Hydrolysis of a Schiff base to carbonyl compound and amine occurs analogously to that of oximes and hydrazones. It is dependent on the basicity of the amine and the reactivity of the aldehyde into which the azomethine is cleaved. Hydrolysis can be achieved in relatively mild conditions, e.g., by short warming in dilute mineral acid, occasionally in dilute alcohol or acetic acid. The condensation products of amines and aldoses are decomposed by even traces of acid Schiff bases are generally resistant to alkali. As in oximes and hydrazones, the aldehyde residue of Schiff bases can be replaced by another aldehyde residue there is a preference for formaldehyde in this case.620... 

Aromatic nitroso compounds are able to condense with numerous compounds containing reactive methylene groups this, the Ehrlich-Sachs reaction,430 affords Schiff bases, whence the corresponding carbonyl compound and amine can be obtained by hydrolysis ... 

These reactions have been sometimes carried out with catalysis by alkoxides,124 but they occur also, often with high yield, in the absence of a catalyst.125 The reaction gains interest because the imine can be replaced by a mixture of carbonyl compound and amine. It is true that reaction of an aldehyde and ammonia (which requires use of a sealed tube or an autoclave) gives only moderate yields,126 but these are higher from aliphatic ketones, ammonia, and dialkyl phosphites — it suffices in some cases to pass dry ammonia into an equimolar mixture of the ketone and phosphite with subsequent heating at... 

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