Synthesis amine reduction

Methamphetannne is a notorious street drug One synthesis involves reductive amination of benzyl methyl ketone with methylamine What is the structure of methamphetamine ... 

Amine synthesis from reductive amination of a ketone and an amine in the presence of excess formic acid, which serves as the reducing reagent by delivering a hydride. When the ketone is replaced by formaldehyde, it becomes Eschweiler-Clarke reductive alkylation of amines. 

Problem 21.2 Synthesize leucine, (CH,),CHCH,CH(NH,)COO, by (a) Hell-Volhard-Zelinsky reaction (Section 16.3) followed by ammonolysis. (b) Gabriel synthesis, (c) phthalimidomalonic ester synthesis, (d) reductive amination of a keto acid, (e) Strecker synthesis (addition of NH, HCN to RCH=0), (/) acetylaminomalonic ester. 

The ready conversion of aldehydes and ketones into oximes and their subsequent reduction is more generally applicable to the synthesis of straight and branched chain primary aliphatic amines. Reduction with sodium and alcohol is convenient and effective and two examples of its use are given in Expt 5.196. 

Protocols of peptide chemistry and, to some extent, biooligomer synthesis (e.g., nucleotides, saccharides) are valuable sources of information on this topic with regards to solid-phase synthesis peculiarities. Here we focus on a particular functional group transformation, which takes the role of depro-tecting a masked functionality, namely the nitro-to-amine reduction. This approach provides a versatile tool for planning multistep derivatizations of heterocycles, as exemplified in Fig. 15.45... 

The isolation of ryllistine (579) represented the first time that a 4-oxygenated norbelladine alkaloid had been isolated from the plants of the family Amaryllida-ceae. The structural assignment was based on spectroscopic methods including a complete assignment of the 13C NMR spectrum combined with its chemical synthesis by reductive amination of veratraldehyde and homoveratrylamine (6). 

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 NaCNBH3 is added to a typical imine-formation reaction it reacts with the products but not with the starting carbonyl compound. Here is an example of an amine synthesis using reductive amination. 

Varlet, J.M., Collignon, N., and Savignac, P, Synthesis and reductive amination of phosphonopyru-vates. Preparation of 2-amino-2-carboxyalkylphosphonic acids (P-phosphonoalanine). Can. J. Chem., 57, 3216, 1979. 

The conversion of prochiral centres in cyclic intermediates into fully blown chiral centres is a profitable way to transmit stereochemical information. The ant trail pheromone monomorine 42 when re-drawn so that we can see all three hydrogen atoms on the same surface of the molecule 42a, is an ideal candidate for synthesis by reductive animation. One of the three centres must be made asymetrically and then the other two set up by reduction of imines formed from that amine and two ketones as in 43. 

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