From Lactams and Imides

Just as lactones and anhydrides can be used to prepare amino acids, their nitrogen analogs (lactams and imides) can also be used. As just seen, and in several previous sections, lactams were generated in an initial reaction and then hydrolyzed to give an amino acid. This section will focus primarily on lactam starting materials and on those reactions for which lactams or imides are key intermediates. 

A very old and useful technique for the synthesis of amino carboxylic acids is the hydrolysis of lactams, as in the conversion of caprolactam 2.44) to 6-amino- 

The hydrolysis of lactams is rather stndghtforward and most of the variety in this table results from different structural features and different synthetic manipulations of the lactams. Reaction I shows a simple hydroly of 3-methyl-2-pyrrolidinone 2.48) to give 2-ethyl-4-aminobutanoic acid 2.49). Several substituted derivatives were prepared, including 2-methyl-4-aminobutanoic acid, 3-ethyl-4 aminobutanoic acid, 3-propyl-4-aminobutanoic acid, 3-(l-methylethyl)-4-aminobutanoic acid, 2,3-diethyl-4-aminobutanoic acid, 2-ethyl-S-aminopentanoic acid, 3-methyl-5-amino-pentanoic acid, 3-ethyl-5-aminopentanoic acid, 3-propyl-5-aminopentanoic acid, and 3-( 1 -methylethyl)-5-aminopentanoic acid. l 

There are many ways to prepare functionalized lactams. Reaction 4 shows an example in which 2.57 was treated with sodium roethoxide to give S-(N-Boc amino)-7-(r-butyldiphenylsilyloxy)heptanoic acid, 2.55. Aqueous acid hydrolysis and 

A different approach to hydroxy amino acids used the allylic bromination of 3-methyl-2-butenoic acid to give a mixture of 2.62 and 2.63, as shown in reaction 6.3 Reaction of this mixture with ammonium hydroxide led to formation of lactam 2.64, which was hydrolyzed to 4-amino-2,3-dihydroxy-3-methylbutanoic acid, 2.65. Hydroxylactams can be converted to functionalized amino acids other than hydroxy amino acids. An example is shown in reaction 7, where 5-fIuoromethyl-2-pyrroli-dinone [2.67) was prepared from 5-hydroxymethyl-2-pyrrolidinone ( .66) by reaction with chlorotrifluorodiethylaminoethane.37 Hydrolysis gave 4-amino-5-fluoropentanoic acid, 2.68. 

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