Studies in polymerization, VIII. Reactions of N -carboxy-α-amino acid anhydrides initiated by metal cations

In the course of an investigation of the reactions of N-carboxy-α-amino-acid anhydrides in polar media (mainly NN-dimethyl formamide solution), it has been found that soluble metallic salts can initiate reactions, including polymerization. This appears to result from the displacement of protons from such organic molecules by metal cations under suitable conditions. The cation forms a complex with the N-carbonic anhydride, which then loses a proton from the —NH— group if this is present. The nitrogen atom in the ring is thus made sufficiently basic to react with another molecule of the carbonic anhydride (see equation (2)). Simple reactions, summarized in equations (3) and (4), then lead to the observed products, cyclic polypeptides and substituted hydantoin 3-acetic acids. A detailed study of the productsobtained from glycine N-carbonic anhydride has been made, and pure cyclic hexaglycine has been isolated in the crystalline state. If the N-carbonic anhydride is N-substituted these reactions cannot occur. A similar kind of initiation can, however, be brought about by the addition of 3-methyl hydantoin. This substance resembles glycine N-carbonic anhydride structurally, and it behaves similarly with metal cations (see equation (5)). The ensuing reaction in the case of sarcosine N-carbonic anhydride leads to a linear polymer, with terminal 3-methyl hydantoin residues and —NHMe groups. The stability of the hydantoin ring precludes the possibility of cyclization reactions. A detailed kinetic study of this reaction of sarcosine N-carbonic anhydride supports the mechanism summarized in equations (13a to ƒ). The molecular weight distributions obtained from polymerizations of this kind have been deduced. The bearing of these results on the spontaneous polymerization of the N-carbonic anhydrides in polar media is discussed briefly.