Amination carbonylative

Monooximes of a-diketones have found applicability in the synthesis of 2-aminopyrazine 1-oxides by condensation with a-aminonitriles, and this reaction was used by White and coworkers in an approach to the synthesis of Cypridina etioluciferamine (Scheme 66 R = 3-indoloyl) (73T3761). In this instance, the use of TiCU as a catalyst was essential, since the carbonyl group in 3-acylindoles is normally deactivated and the required amine/carbonyl condensation is impractically slow. Under normal circumstances the carbonyl group in simple alkyl-substituted monoximes of a-diketones is the more reactive site and the reaction is rapid, requiring no catalysis (69LA(726)loo). 

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. 

Type I MCRs are usually reactions of amines, carbonyl compounds, and weak acids. Since all steps of the reaction are in equilibrium, the products are generally obtained in low purity and low yields. However, if one of the substrates is a bi-funchonal compound the primarily formed products can subsequently be transformed into, for example, heterocycles in an irreversible manner (type II MCRs). Because of this final irreversible step, the equilibrium is forced towards the product side. Such MCRs often give pure products in almost quantitative yields. Similarly, in MCRs employing isocyanides there is also an irreversible step, as the carbon of the isocyanide moiety is formally oxidized to CIV. In the case of type III MCRs, only a few examples are known in preparative organic chemistry, whereas in Nature the majority of biochemical compounds are formed by such transformations [3]. 

In addition, the six- to eight-membered lactams like 48, 49, and 50 have been formed from amines, carbonyl-carboxylic acids, and isocyanides (Scheme 1.14). 

Reductions of isolated double bonds in alcohols, amines, carbonyl compounds, acids, etc., are discussed in the appropriate sections. 

Fluorination has an important indirect impact on hydrogen bonds, via neighbouring functions (hydroxyl, amine, carbonyl, hydrogen). The electron-withdrawing effect of fluorine atom and of fluoroalkyl groups (CF2, CF3, etc.) deeply modifies the pKg of neighbouring functions, and hence their character of hydrogen bond donors or acceptors (Table 1). 

Ethers, sulfides, amines, carbonyl compounds, and imines are among the frequently encountered Lewis bases in the ylide formation from such metal carbene complex. The metal carbene in the ylide formation can be divided into stable Fisher carbene complex and unstable reactive metal carbene intermediates. The reaction of the former is thus stoichiometric and the latter is usually a transition metal complex-catalyzed reaction of a-diazocarbonyl compounds. The decomposition of a-diazocarbonyl compounds with catalytic transition metal complex has been the most widely used approach to generate reactive metal carbenes. For compressive reviews, see Refs 1,1a. 

Thus, precursors such as hydrocarbon ethers, amines, carbonyl compounds which are readily protonated tend to be more amenable to ECF than, say, hydrocarbons or halocarbons whose solubilities and conductivities are low. A number of techniques have been developed in the past decade, however, to overcome such problems (see Sect. 4.2). Similarly, advances in methodology of ECF now allow the fluorination of gaseous, liquid, solid, and even polymeric materials [72-77]. 

Amine Carbonylation Catalyzed by Ruthenium Complexes under Mild Conditions... 

Since many ruthenium species, including ammines, are readily carbonyl-ated using carbon monoxide under mild conditions (4, 5), there seemed a good probability that effective ruthenium catalysts could be found for amine carbonylation under mild conditions. Product selectivity, a problem at more severe conditions, should also improve. 

Kinetic studies on catalytic amine carbonylation reactions are scarce, although Brackman (13) has reported kinetics on a copper(I)-copper(II) catalyzed production of ureas from cyclic secondary amines using carbon monoxide-oxygen mixtures at ambient conditions. Saegusa and coworkers (14) used cuprous salts and other group IB and IIB metal compounds to car bony late piperidine to N-formylpiperidine under more severe conditions. We have published (15) a brief report involving some of the studies described in this paper. 

Numerous dinucleating macrocyclic and macrobicyclic ligands have been synthesized, in particular by the versatile amine + carbonyl — imine reaction they form dinuclear metal complexes as well as cascade complexes with bridging groups [2.58-2.63, 3.24-3.27, 4.1-4.4], for instance in dicobalt complexes that are oxygen carriers [3.26]. 

Keywords primary amine, carbonyl compound, gas-solid reaction, /V-alkyl-azo-methine... 

While this notion may conjure up visions of plastic materials it is important to remember that proteins and nucleic acids are also polymers. Many proteins form globular structures and, indeed, may interlock to encapsulate a large volume of space as exemplified by the coatings of capsid viruses. In a prebiotic world, polypeptides could have formed in aqueous solution through the sequential reaction of amino acids. The individual amino acids hydrogen bond donor and acceptor groups, amines, carbonyls and carboxylic acids, would all have helped to keep the molecules in solution. Once a polypeptide had formed, however, many of these would be unavailable as they became incorporated in the hydrogen bond network that formed the secondary and tertiary structure. This would result in a more hydrophobic surface for the protein capsule which would make an effective cell. 

By the action of ammonia, primary or secondary amines, carbonyl groups can be converted, in the presence of hydrogen and a suitable catalyst, to primary, secondary, or tertiary amines. This reaction has proved to be a useful tool in the field of synthetic organic chemistry. The conversion can be formulated as follows ... 

Valuable orgartic solvents, such as formamides, arc available from HCN aird these syntheses could be interesting substitute methods for ammonia or amine carbonylation reactions. Formamide is formed during the hydrolysis of HCN under dilute, slightly basic conditions (pH 7-10). with polymers being formed in concentrated solutions (Section 3.4). Dimethyl formamide can be obtained from HCN and CH3OH in the presence of T1CI4 or TeCU as catalysts 43]. 

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