Amines selective reduction

FORSTER - DECKER Amine Synthesis Selective monoalkylation of primary amines via imines An altemativa method is the reaction ol 1 and 2 in the preserve of NaCNBH4 or tnaceloxyborohydride (Borch reduction)/... 

Selectivities of about 2 1 are the best found for this type of hydrogenation and are highly dependent on the secondary amine used they seem to correlate with the nucleophilicity of the amine. Reductive amination of PhCHO with ben-zylamine can proceed through an imine intermediate, and thus gave better selectivities (12 1) but was found to be sluggish using this catalyst system. 

The reduction is usually effected catalytically in ethanol solution using hydrogen under pressure in the presence of Raney nickel. As in the reduction of nitriles (Section 5.16.1, p. 771), which also involves the intermediate imine, ammonia or the amines should be present in considerable excess to minimise the occurrence of undesirable side reactions leading to the formation of secondary and tertiary amines. These arise from the further reaction of the carbonyl compound with the initially formed amine product. Selected experimental conditions for these reductive alkylation procedures have been well reviewed.210 Sodium borohydride has also been used as an in situ reducing agent and is particularly effective with mixtures of primary amines and aliphatic aldehydes and ketones.211... 

Aromatic nitro compounds (ArN02), are much more electroactive, and specific reduction steps are seen even in acidic aqueous buffers (e.g. at mercury pool cathodes). In general, two successive steps are observed (a four-electron step followed by a two-electron step) with the formation of hydroxylamine and amine, respectively. The reduction selectivity is therefore very sensitive to the potential applied. 

Reductive amination. Reductive amination of 3-ketosteroids with ammonia, hydrogen, and Pd-C gives 3)3-aminosteroids, but in poor yield. It is preferable to use benzylamine the intermediate secondary amine undergoes hydrogenolysis. The reaction is selective for 3-ketosteroids carbonyl functions at C17 and Cm are not affected. Thus hydrogenation of progesterone in the presence of benzylamine and Pd-C afforded 3/3-amino-5)3-pregnane-20-one in 71% yield. 

Fig. 15.4-9 Prototype structu res of the Novartis TAM combinatorial libraries generated through reductive amination of selected aldehydes and secondary amines. The new structures for which examples are shown in (b) were designed to be similar to known monoamine CPCR ligands for which examples are shown in (a). Ligands, which are of the size of the endogenous ligands, are herein called simple - one-site filling...

A -Substituted bornyl- and isobornylamines 17-19 are best obtained by reduction of the imines formed from camphor and a suitable amine4, either by isolation of the imine or in situ formation. The substituted amines were used as the lithium salt for enantioselective deprotonation and elimination reactions (Section C ). In almost all cases, the exo-amines (isobornylamines) are formed however, using (S)-l-phenylethylamine as the starting amine, the selectivity is reversed and the enob-amine (bornylamine) is obtained. 

Primary Amines. - Reductive methods in the preparation of amines continue to be popular. In particular, anilines can be prepared under mild conditions and in good yields by reduction of nitrobenzenes with the new system of diborane-nickel (II) chloride." Selective reduction in the presence of a number of functional groups is the chief advantage of the method. Nitrobenzenes are also... 

Irradiation of N-tosylamines in aqueous ethanol in the presence of an aromatic electron donor such as 1,4-dimethoxybenzene, and a reductant such as sodium borohydride induced detosylation and liberation of the corresponding primary or secondary amine 70 selective deprotection of some Ne- tosyl-lysine peptides was successful. 

Aromatic or aliphatic nitriles are unreactive towards Sml2- Nitroaro-matics are rapidly reduced to amines. Some selective reductions are then... 

Keywords Aromatic azides, BF3.0Et2/NaI, MeCN, room temperature, selective reduction, amines, reductive-cyclization, pyrrolo[2,l-c][l,4]benzodiazepines... 

In the last steps, all that remained was to reduce the azide and methylate the resulting amine. Reduction of azide was cleanly effected by hydrogen over Pd/C. The problem of selectivity in reduction of carbamate to Me group was circumvented, however, by using LiAlH(OMe3) in refluxing THE. 

Imines were preferentially formed and the carbon-carbon bond was selectively formed at the C(2) position of the cyclic amine. With ethylene and propene, only imines were formed but with more bulky olefins and 7-membered cyclic amines, reduction to 2-alkyl cyclic amine took place, and N-alkylation was also observed from bicyclic amine. 

Recently, an interesting example of a redox neutral cascade using co-TAs for the key reductive amination step was presented [37]. This enzymatic activity, catalyzing the reductive amination of selected aldehydes, was coupled with an ADH for the... 

It is convenient to include under Aromatic Amines the preparation of m-nitroaniline as an example of the selective reduction of one group in a polynitro compound. When wt-dinitrobenzene is allowed to react with sodium polysulphide (or ammonium sulphide) solution, only one of the nitro groups is reduced and m-nitroanUine results. Some sulphur separates, but the main reaction is represented by ... 

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