Carbonyl Compounds amines with

An alkene activated by an electron-withdrawing group—often an acrylic ester 2 is used—can react with an aldehyde or ketone 1 in the presence of catalytic amounts of a tertiary amine, to yield an a-hydroxyalkylated product. This reaction, known as the Baylis-Hillman reaction, leads to the formation of useful multifunctional products, e.g. o -methylene-/3-hydroxy carbonyl compounds 3 with a chiral carbon center and various options for consecutive reactions. 

Interestingly, comparison of the values of pAHB and the acidity constants pKa in a series of the same family of compounds, such as carbonyl compounds, amines, pyridines and sulphoxides, shows that a good correlation exists between p/CHB and pgiving straight lines in each series of compounds with parallel slopes. This enables one to calculate the difference of the several pKa values at the same p/CHB value, and vice versa. Thus, at p= 0, p/CHB values of various functional groups were determined and are shown in Table 13. 

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 tris[3-trifiuoroacetyl-Lanthanide shift reagents have the property of spreading NMR peaks of compounds with which they can form coordination compounds, for examples, alcohols, carbonyl compounds, amines, and so on. Chiral lanthanide shift reagents shift the peaks of the two enantiomers of many such compounds to different extents. 

The direct reductive amination (DRA) is a useful method for the synthesis of amino derivatives from carbonyl compounds, amines, and H2. Precious-metal (Ru [130-132], Rh [133-137], Ir [138-142], Pd [143]) catalyzed reactions are well known to date. The first Fe-catalyzed DRA reaction was reported by Bhanage and coworkers in 2008 (Scheme 42) [144]. Although the reaction conditions are not mild (high temperature, moderate H2 pressure), the hydrogenation of imines and/or enam-ines, which are generated by reaction of organic carbonyl compounds with amines, produces various substituted aryl and/or alkyl amines. A dihydrogen or dihydride iron complex was proposed as a reactive intermediate within the catalytic cycle. 

The reaction shown in Scheme 39 was also performed starting from a chiral carbamoyl chloride (91, Y = O) derived from (f )-iV-methyl-iV-(l-phenylethyl)amine, in order to study the possible asymmetric induction using prochiral carbonyl compounds. Thus, with pivalaldehyde or benzaldehyde the mixture of diastereomers obtained was ca 1 1. This behavior was also observed with other chiral functionalized organolithium compounds ". ... 

Ugi, I. and Steinbruckner, C. (1961) Isonitriles. II. Reaction of isonitriles with carbonyl compounds, amines, and hydrazoic acid. Chem. Ber. 94, 734-742. 

Primary amines have been transformed into imines which when metallated react with carbonyl compounds. Treatment with butyllithium, alkylation with allyl bromide and hydrolysis gives highly substituted aldehydes (Scheme 6). Thus, in this example, the carbon adjacent to the original amino nitrogen atom becomes the carbonyl carbon. The technique has been used several times in the course of total synthesis, as with a recent approach to crinine and as the key step in a recent highly regioselective preparation of a,3 unsaturated aldehydes (equation 33). ... 

Draw the products formed when each carbonyl compound reacts with the following amines [1] CH3CH2CH2NH2 [2] (CH3CH2)2NH. 

Carbon disulfide, as the thio analog of carbonyl compounds, reacts with primary amines with resultant formation of alkyl isothiocyanates, which have lower... 

Schmidt Reaction.54 Closely related to the Curtins reaction in its mechanism is the Schmidt reaction, whereby carbonyl compounds react with hydrazoic acid in acid solution to give rearranged products. Amines, amides, nitriles, and tetrazoles are the most common substances obtained from the reaction. 

A similar MW strategy has been used to synthesize a set of pyrimidinones (65-95%) via the Biginelli condensation reaction in a household MW oven and has been successfully applied to combinatorial synthesis [139]. More recent examples describe a convenient synthesis of highly substituted pyrroles (60-72%) on silica gel using readily available a, 3-unsaturated carbonyl compounds, amines, and ni-troalkanes [140], and the use of neat reactants under solvent-free conditions to generate Biginelli and Hantzsch reaction products with enhanced yields and shortened reaction times [141]. 

Oxidation of N-cMoroamines to carbonyl compounds. Amines can be eonver-ted into carbonyl compounds by conversion to N-chloroamines (1, 92), which are not isolated but are oxidized directly with KO2 in the presence of 18-crown-6. The intermediate imines are then hydrolyzed. ... 

The reaction products with secondary amines could not be isolated in pure form, but since they are aminoacetals of the corresponding carbonyl compound, hydrolysis with water to LI is easily accomplished... 

This can be done in two steps, provided the intermediate is stable, but, because the instability of many imines makes them hard to isolate, the most convenient way of doing it is to form and reduce the imine in a single reaction. The selective reduction of iminium ions (but not carbonyl compounds) by sodium cyanoborohydride makes this possible. When Na(CN)BH3 is added to a typical imine-formation reaction it reacts with the iminium ion but not with the starting carbonyl compound nor with the imine. Here is an example of an amine synthesis using reductive amination. 

Carbon disulfide as the thio-analog of carbonyl compounds reacts with primary amines, resulting in the formation of alkyl isothiocyanates, which have slightly lower RIs than those of other derivatives of primary amines, including A -trimethylsilylated amines (Table 5). The sole product of this reaction is gaseous hydrogen sulfide ... 

Carbonyl compounds condense with amines and related functional groups (e.g., hydrazines), with elimination of water, to yield C=N double-bonded products ... 

Amines and alcohols are oxidized to the corresponding imine (or iminium ion) and carbonyl compounds, respectively, with palladium catalysts. Coordination of heteroatom to palladium, insertion of palladium into hydrogen-heteroatom bonds, and /3-elimination of palladium hydride species are involved in these reactions. 

El Kaim et al. extended the Ugi-Smiles methodology to the preparation of new heterocyclic scaffolds 109 by coupling of 2-hydroxypyridines or pyrimidines (108) with carbonyl compounds, amines, and isocyanides [1(X)]. The scope was further extended using heterocyclic thiols to form highly functionalized thioamides (Scheme 7.43) [101]. 

---