Urethanes aminolysis

An additional minor source of urethane can be the reaction of unconsumed reagent with V-nucleophile (path C). Aminolysis of chloroformate occurs if there is an excess of reagent or if the anhydride-forming reaction is incomplete. The latter is more likely when the residues activated are hindered. This side reaction can be avoided by limiting the amount of reagent and extending the time of activation. A third side reaction that is of little consequence is disproportionation of the mixed anhydride to the symmetrical anhydride and dialkyl pyrocarbonate (see Section 7.5). 

FIGURE 2.27 More on additives. In a carbodiimide-mediated reaction between acid 1 and amine 2, addition of HOObt can lead to the side reaction of aminolysis at the carbonyl of the activating moiety of ester 3, generating addition product 4. Addition of HOBt to a mixed-anhydride reaction containing unconsumed chloroformate generates mixed carbonate 5, leading to production of urethane 6. 

There is a claim that HOBt suppresses undesired aminolysis at the carbonate carbonyl of a mixed anhydride (Figure 2.25, path F). It is rarely used for this purpose, but if it is, it must be added only after the chloroformate has been consumed otherwise, mixed carbonate 5 is formed, and it depletes the amino-containing component by acylating it, giving stable urethane 6 (Figure 2.27).2 UI 3477... 

FIGURE 7.4 The mixed-anhydride reaction (see Section 2.6). Preparation of mixed anhydride 4 followed by its aminolysis (A) producing peptide 6 and the major side reaction of aminolysis at the wrong carbonyl (B) generating urethane 7. 

The major side reaction associated with the use of mixed anhydrides is aminolysis at the carbonyl of the carbonate moiety (Figure 7.4, path B). The product is a urethane that resembles the desired protected peptide in properties, except that the amino-terminal substituent is not cleaved by the usual deprotecting reagents. Hence, its removal from the target product is not straightforward. The problem is serious when the residues activated are hindered (Val, lie, MeXaa), where the amounts can be as high as 10%. Other residues generate much less, but the reaction cannot be avoided completely, with the possible exception of activated proline (see Section 7.22). This is one reason why mixed anhydrides are not employed for solid-phase synthesis. 

There have been reports that urethane was produced when the mixed-anhydride method was employed for the coupling of segments. However, studies on urethane formation during the aminolysis of mixed anhydrides of peptides have never been carried out. The anhydrides are too unstable to be isolated. The activated moiety of the peptide cyclizes too quickly to the 2,4-dialkyl-5(4//)-oxazolonc (see Section 2.23), and since the time allowed to generate the anhydride in segment couplings is always limited to avoid epimerization, one cannot exclude the possibility that the urethane that was produced originated by aminolysis of unconsumed chloroformate. 

In fact, recent work indicates that less urethane is formed by aminolysis of an activated peptide than by aminolysis of an activated /V-al ko x y carbon y I am ino acid. Such results are consistent with the postulate that the intermediate undergoing aminolysis during the mixed anhydride reaction of a segment is the 2,4-dialkyl-5(4//)-oxazolonc, a tenet that is indicated by the high rate at which the activated peptide is converted to the oxazolone.10 13... 

FIGURE 7.34 Decomposition of the symmetrical anhydride of A-methoxycarbonyl-valine (R1 = CH3) in basic media.2 (A) The anhydride is in equilibrium with the acid anion and the 2-alkoxy-5(4//)-oxazolone. (B) The anhydride undergoes intramolecular acyl transfer to the urethane nitrogen, producing thelV.AT-fcwmethoxycarbonyldipeptide. (A) and (B) are initiated by proton abstraction. Double insertion of glycine can be explained by aminolysis of the AA -diprotected peptide that is activated by conversion to anhydride Moc-Gly-(Moc)Gly-0-Gly-Moc by reaction with the oxazolone. (C) The A,A -diacylated peptide eventually cyclizes to the IV.AT-disubstituted hydantoin as it ejects methoxy anion or (D) releases methoxycarbonyl from the peptide bond leading to formation of the -substituted dipeptide ester. 

The chemical splitting of ester bonds by hydrolysis, alcoholysis or aminolysis are specific reactions of all organic esters, including urethanes (or carbamates) which are in fact esters of carbamic acid. 

For a better understanding of the PU foam wastes recovery by chemical processes. The model reactions for hydrolysis, glycolysis and aminolysis of urethane and urea groups will be presented in the next sections. 

Encouraged by the successful model reaction, implementation of the radical amine-thiol-ene conjugation in synthetic polymer science was envisaged. Consequently, several AB -type monomers containing both a double bond and a thiolactone unit were prepared. Upon aminolysis, these monomers form a reactive thiol-ene, which is consumed in the same medium in a stepwise polyaddition. It is clear that the nature of the introduced double bond and chemical linkage (amide, urethane, etc.) connecting the thiolactone and double bond determine both the reaction conditions and outcome of the two-step process, as well as the final properties of the synthesized polymers. 

FVom the point of view of the application of ester, amide, and urethane polymers, hydrolysis, alcoholysis/glycolysis and ammonolysis/aminolysis reactions are the most important. These processes are often used for recycling to feedstocks and offer raw materials, mainly for virgin polymer/resin syntheses. The schemes of the respective reactions with brief comments on the practical importance of the particular processes are presented in Figures 2 to 4. A description of the important solvolytic degradation processes for ester, amide, and urethane polymers is also given in this chapter. 

---