Amides to protect amines

Acylation of norephedrine (56) with the acid chloride from benzoylglycolic acid leads to the amide (57), Reduction with lithium aluminum hydride serves both to reduce the amide to the amine and to remove the protecting group by reduction (58), Cyclization by means of sulfuric acid (probably via the benzylic carbonium ion) affords phenmetrazine (59), In a related process, alkylation of ephedrine itself (60) with ethylene oxide gives the diol, 61, (The secondary nature of the amine in 60 eliminates the complication of dialkylation and thus the need to go through the amide.) Cyclization as above affords phendimetra-zine (62), - Both these agents show activity related to the parent acyclic molecule that is, the agents are CNS stimulants... 

Alkyl-4-oxo-l,3-dioxolanes, to protect a-hydroxy carboxy groups, 267 5-Alkyl-4-oxo-l,3-dioxolanes, to protect a-hydroxy carboxy groups, 267 4-Alkyl-5-oxo-l,3-oxazolidines, to protect carboxy groups, 266-267 Allyl alcohols, to protect, 18 iV-Allylamides, to protect amides, 154, 397 /V-Allylamines, to protect amines, 362 Allyl carbamates, to protect amines, 248, 252, 331-332... 

Amines, protection of, 309-405 as amides, 348-362 Reactivity Chart 9, 445-449 as carbamates, 315-348 Reactivity Chart 8, 441-444 as special derivatives, 362-385 Reactivity Chart 10, 449-452 Amino acetal derivatives, to protect amines, 392-394... 

Carboxylic acids, protection of, 224-276 as amides and hydrazides, 270-276 as esters, 227-270 Reactivity Chart 6, 433-436 S-Carboxymethyl thioethers, to protect thiophenols, 294-295 Catechols, protection of, 170-174 as cyclic acetals and ketals, 170-172 as cyclic esters, 173-174 Reactivity Chart 4, 425-428 CBZ, see Benzyl carbamates Chloroacetamides, to protect amines, 352-353... 

The nucleophilicity and basicity of an amine nitrogen is vitiated by incorporation into an imide or amide linkage. The imides and amides are easily prepared by reaction of the amine with the appropriate add chloride or anhydride in the presence of a base. Amides are generally stable towards acid and base and require brutal conditions to hydrolyse them, but the small group used to protect amines was selected for their high susceptibility to nucleophilic attack. 

Acyloxymethylbenzoic acids can be used to protect amines.93 The amides so derived can be cleaved with mild acid or base due to neighboring group participation of the generated alcohol. 

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