Special NH Protective Groups

SPECIAL-NH PROTECTIVE GROUPS Af-Alkyl and /V-Aryl Amines 

The methyl group, although inert to many chemical transformations, is not often considered a good protective group because of the perceived difficulty in its removal, hut as illustrated there are a number of methods that can be used to cleave an W-methyl group in highly functionalized substrates. 

Methylamines are commonly formed by reacting the amine with a methylating agent such as Mel or dimethyl sulfate. 

Preparation from an amine and TMSCHN2 (HBF4, CH2CI2, H2O) has also been explored. 

For primary aromatic amines dimethyl carbonate, Y-zeolite, 130-150°C, 72-93% yields. Y-faujasites have been used as catalysts and require lower temperatures to achieve methylation. CO2 must be removed with a stream of N2 to prevent carbamates formation.  

For primary aromatic amines dimethyl carbonate, Y-Zeolite, 130-150°, 72-93% yields.  

The cleavage of a methylamine can be accomplished photochemically in the presence of an electron acceptor such as 9,10-dicyanoanthracene.  

Allylamines have been used as nitrogen protective groups. They can be removed by isomerization to the enamine (t-BuOK, DMSO) or by rhodium-catalyzed isomerization.  

The SEM derivative of a secondaiy aromatic amine, prepared from SEMCl (NaH, DMF, 0°, 100% yield), can be cleaved with HCl (EtOH, 88% yield).  

A 3-acetoxypropyl group was used to protect an aziridine — NH group during the synthesis of mitomycins A and C acetyl, benzoyl, ethoxycarbonyl, and methoxymethyl groups were unsatisfactory.  

7V-(l-Isopropyl-4-nitro-2-oxo-3-pyrrolin-3-yl)amine Formation/Cleavage  

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I-Substituted 3,5-Dinitro-4-pyridonyl, 360 SPECIAL -NH PROTECTIVE GROUPS N-Alkyl and A-Aryl Amines... 

Reactivity Chart 10. Protection for the Amino Group Special —NH Protective Groups... 

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