Nucleophilic catalysis in the nitrosation of sarcosine and proline

Abstract

The formation of nitrosoamino acids from both sarcosine (Sar) and proline (Pro) and nitrous acid is very strongly accelerated by thiourea (TU) and tetramethylthiourea (TMTU), and to a lesser extent by thiocyanate ion. The effects of TU and TMTU are very similar and are greater than that of SCN^– by a factor of 17 for Sar and 30 for Pro. Thus these amino acids behave like amines and not like amides (where there is no nucleophilic catalysis). The second-order rate constants (k₂) for XNO [ONSCN or ONSC(NR₂)₂] attack were obtained (a) from the variation of the observed rate constant (k_o) with [X^–] or [X] and (b) from the variation with [substrate]. The agreement is excellent. This analysis assumes that reaction occurs as N-nitrosation of the free –NH– function. The variation of k_o with acidity, however, shows that there is another (small) component to the reaction, and the results are consistent with an earlier idea involving initial O-nitrosation at the –CO₂^– function. The k₂ values are discussed with reference to the reaction of other substrates with these (and other) nitrosating reagents, particularly with reference to encounter-controlled processes. The extent of the alternative pathway for ONSC(NH₂)₂ decomposition is assessed in relation to the ability of this species to act as a nitrosating agent.