Hydrogenation carbon-nitrogen double bonds

For a review, see Harada, K. in Patai The Chemistry of the Carbon-Nitrogen Double Bond, Ref. 40, p. 276. For a review with respect to catalytic hydrogenation, see Rylander, P.N. Catalytic Hydrogenation over Platinum Metals, Ref. 165, p. 123. 

The use of chiral amide ligands has been restricted to rhodium, where the catalyst precursor is [Rh(BH4)(amide)py2Cl2]. The work has been reviewed (10, 35) cinnamate derivatives were reduced to up to 57% ee, and hydrogenation of a carbon- nitrogen double bond in folic acid leads to tetrahydrofolic acid with high biological activity (308). 

In this chapter and in Chapters 10-12, we will review and validate some methods for asymmetric (transfer) hydrogenation of carbon-oxygen and carbon-carbon double bonds catalysed by non-metallic systems, homogeneous transition metal catalysts and biocatalysts. Reduction of carbon-nitrogen double bond systems will be reported in another volume of this series. 

The carbon-nitrogen double bond of A1-piperideines is susceptible to reduction. This can be useful for the stereospecific introduction of ring substituents. An illustration is the preparation of ds-2,6-disubstituted piperidines (211) by catalytic hydrogenation of the corresponding A1-piperideine (210) (77T1569). 

Reaction of 2-chloropyridine gives 2-chloro-6-fluoropyridine as the major product which arises from the preferential substitution of hydrogen over chlorine and would be unexpected on the basis of the nucleophilic substitution mechanism described above. The product obtained was suggested, therefore, to arise from the addition of fluorine to the most electron rich carbon-nitrogen double bond, followed by elimination of HF [155]. 

It is postulated that the facile cleavage of the complex is due to the polarization of the carbon-nitrogen double bond. At pH 7, where these investigations were carried out, the spontaneous decomposition of the Schiff base is very slow, while the metal ion-catalyzed reaction has a half life of a few minutes. Since the hydrolysis of Schiff bases is catalyzed by hydrogen ion, the metal ion catalyst can be postulated to be a superacid catalyst present in neutral solution (17, 18). 

The carbon-nitrogen double bond of phenanthridine can be reduced selectively by hydrogenation over Raney nickel, and attempted reductive dechlorination of 6-chloro derivatives in the presence of this catalyst normally results in the formation of the corresponding 5,6-dihydro compounds.106 Hydrogenations over palladium catalysts are more successful.203 325 Desulfurization of phenanthridinthione... 

Addition of Hydrogen Cyanide to Carbon-Nitrogen Double Bonds. 606... 

Hydrogen cyanide adds to the carbon-nitrogen double bonds present in various aldehyde and ketone derivatives, like those in imines, hydrazones, oximes, and Schiff bases. In each instance, a new carbon-carbon linkage is formed. Thus, the reaction of dry hydrogen cyanide with an imine... 

The carbon-nitrogen double bonds of oximes and hydrazones are hydrogenated to form the corresponding amines by heterogeneous catalytic hydrogenation. 

Numerous asymmetric catalytic hydrogenations of carbon-nitrogen double bonds have been carried out. Some of the substrates used are oximes and hydrazones, but most of the reactions were carried out using Schiff s bases of ketones. a-Keto acids are precursors of a-amino acids in biosynthesis, and therefore a-keto acids have been used for the asymmetric syntheses of a-amino acids. ... 

Heterogeneous catalytic hydrogenation of a carbon-nitrogen double bond over a metal catalyst in the presence of a chiral compound was first carried out by Nakamura. Acetophenone oxime was hydrogenated over platinum black with ethyl menthoxyacetate or tartaric acid to give a-methylbenzylamine with 15-18% ee. 

Isocyanates have three possible resonance states, as shown in Figure 2.18. The reaction occurs by addition to the carbon-nitrogen double bond. In case of compounds with active hydrogen, the hydrogen atom becomes attached to the nitrogen of the isocyanate and the remainder of the active hydrogen compound becomes attached to the carbonyl carbon ... 

Dehydrogenations, which involve the elimination of hydrogen Ifom organic molecules, lead to compounds containing double bonds, multiple bonds, or aromatic rings. For practical reasons, only the formation of carbon-carbon double bonds, of carbon-nitrogen double bonds in cyclic amines, and of aromatic rings (both carbocyclic and heterocyclic) will be discussed in this chapter. The conversion of alcohols into aldehydes and ketones and of amines into imines and nitriles will be discussed in the chapter Oxidations (Chapter 3). 

This approach should be useful in determining the direction of hydrogenation for molecules in which the carbinol group is replaced by carbon-carbon or carbon-nitrogen double bonds. With an alkene, though, the simple conformational model would have to be used and the hydrogenation should be run under conditions that do not promote double bond isomerization, that is, not with palladium or nickel catalysts. With carbonyl compounds the preferred eonditions for selective reaction involve platinum, rhodium or ruthenium catalysts imder non-diffusion control conditions. The use of nickel catalysts, especially Raney nickel, with its basic components, can cause an equilibration of the alcohol product. 

Quaternary ammonium compounds - Derivatives of ammonium compounds, Y , in which all four of the hydrogens bonded to nitrogen have been replaced with hydrocarbyl groups. Compounds having a carbon-nitrogen double bond (i.e. R2C=N+R2Y ) are more accurately called iminium compounds. [5]... 

Hydroxylamine hydrochloride (HO-NHa Cl) is a derivative of ammonia. It can react with the carbonyl carbon to form a carbon-nitrogen double bond. The reaction rate is enhanced by acid. This can be readily seen in the reaction mechanism. The proton attaches itself to the carbonyl oxygen rendering a more positive dipole to the carbon, which is now more susceptible to nucleophilic attack by nitrogen. The mechanism is shown below, R can be hydrogen or alkyl group. 

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