Carbamic acid reactivity

Step-growth polymerization processes must be carefully designed in order to avoid reaction conditions that promote deleterious side reactions that may result in the loss of monomer functionality or the volatilization of monomers. For example, initial transesterification between DMT and EG is conducted in the presence of Lewis acid catalysts at temperatures (200°C) that do not result in the premature volatilization of EG (neat EG boiling point 197°C). In addition, polyurethane formation requires the absence of protic impurities such as water to avoid the premature formation of carbamic acids followed by decarboxylation and formation of the reactive amine.50 Thus, reaction conditions must be carefully chosen to avoid undesirable consumption of the functional groups, and 1 1 stoichiometry must be maintained throughout the polymerization process. 

The isocyanate group is reactive, a feature which leads to a large number of possible reactions when crosslinking is carried out. The essential feature of all the processes is that they involve reaction, initially at least, with an active hydrogen atom in the molecules of the co-reactant. For example, isocyanates will react with water, as illustrated in Reaction 4.10, to generate an unstable intermediate, a carbamic acid, which releases carbon dioxide to yield an amine. 

Beagents for the derivatization of alcohols show variable reactivity and those containing an acid chloride or nitrile group require anhydrous conditions. DMOQ-CONj is the only reagent that reacjts to a significant extent with tertiary alcohols. The product of the reaction is a carbamic acid ester. Detection limits for alcohol derivatives are also frequently nc e than modest... 

Initially, water can cause the hydrolysis of the anhydride or the isocyanate, Scheme 28 (reaction 1 and 2), although the isocyanate hydrolysis has been reported to occur much more rapidly [99]. The hydrolyzed isocyanate (car-bamic acid) may then react further with another isocyanate to yield a urea derivative, see Scheme 28 (reaction 3). Either hydrolysis product, carbamic acid or diacid, can then react with isocyanate to form a mixed carbamic carboxylic anhydride, see Scheme 28 (reactions 4 and 5, respectively). The mixed anhydride is believed to represent the major reaction intermediate in addition to the seven-mem bered cyclic intermediate, which upon heating lose C02 to form the desired imide. The formation of the urea derivative, Scheme 28 (reaction 3), does not constitute a molecular weight limiting side-reaction, since it too has been reported to react with anhydride to form imide [100], These reactions, as a whole, would explain the reported reactivity of isocyanates with diesters of tetracarboxylic acids and with mixtures of anhydride as well as tetracarboxylic acid and tetracarboxylic acid diesters [101, 102]. In these cases, tertiary amines are also utilized to catalyze the reaction. Based on these reports, the overall reaction schematic of diisocyanates with tetracarboxylic acid derivatives can thus be illustrated in an idealized fashion as shown in Scheme 29. 

Nitrenes, like carbenes, are immensely reactive and electrophilic, and the same Wolff-style migration takes place to give an isocyanate. The substituent R migrates from carbon to the electron-deficient nitrogen atom of the nitrene. Isocyanates are unstable to hydrolysis attack by water on the carbonyl group gives a carbamic acid which decomposes to an amine. 

Reaction sequence I should be favoured under conditions when the carbamic acid is relatively stable but is fairly reactive toward the isocyanate. Sequence II would be favoured when the carbamic acid decomposes rapidly and the amine thus liberated reacts quickly with the isocyanate. This sequence is the one most often given in simplified discussions of the isocyanate/water reaction. Sequence III might increase in significance when the carbamic acid is not stable but the amine and the... 

There are a few other chemical reactions on the wood surface that could make important contributions. One is that of moisture on the surface of wood to form an unstable carbamic acid group that quickly decomposes to form a primary amine with evolution of carbon dioxide. The primary amine formed has active hydrogens reactive to isocyanate. Other successive reactions ensue leading first to disub-stituted ureas and then to biurets. Furthermore, isocyanate reaction with urethane to form allophanates, and trimerization of isocyanates to form isocyanurate are also possible to variable extents, under the conditions of bonding. The different reactions are summarized in Scheme 2. 

The relative rates of these reaction sequences were found to depend on the nature of the medium (homogeneous or heterogeneous), rate of addition of water, temperature, reactivity of the amine (formed by the decomposition of the carbamic acid) with the isocyanate, concentration, and other factors. For example, in the reaction with phenyl isocyanate, cold water and heterogeneous medium favored the formation of diaryl urea while with boiling water the main product was aniline. Dilution also favored aniline formation. 

It has been almost 40 years since B. Wilson et al. observed that nucleophiles, oximes like hydroxamic acid, reactivated OP-inhibited AChE above and beyond that occurring from spontaneous reactivation, opening the way to a treatment for OP poisoning. The oxime registered for use in the United States is 2-PAM Cl (Protopam) its methanesulfonate salt (P2S) is used in Europe. Oxime therapy should be recommended with caution for carbamate poisonings. Although beneficial in the case of aldicarb, there is evidence that 2-PAM treatment increases the toxicity of carbaryl. 

Chemical interactions of CO2 with substrates, products or catalysts can also play a major role in defining rate and selectivity of a given reaction. This chemical influence must not necessarily be positive, making it even more important to remember that CO2 does not always provide an inert medium. For example, hydrogen carbonate and protons are generated in the presence of water (pH = 3), carbamic acids or carbamates are formed with basic N-H functionalities, and the coordination ability and reactivity towards various transition metal centers is well established [20]. One of the appealing prospects of the chemical reactivity of CO2 is its simultaneous use as solvent and Cj building block in metal-catalyzed processes. 

The reactivity of these prodrugs varies considerably. Whereas most of them are activated enzymatically, others are activated nonenzy-matically, as discussed in the following paragraphs. Enzymatic hydrolysis followed by chemical breakdown is another possibility (e.g., carbamic acids formed from carbamates). 

Riffle, J. S. 1988. Discussion of gas phase reactivity of amines with carbamic acids. Private communication, Virginia Polytechnic Institute and State University. 

The CM anticholine.sterases are thought to inhibit AChE and BuChE in a manner similar to that of OPs. However, instead of an electrophilic pho,sphorus, as in the case of the OPs, CMs contain an electrophilic carbonyl carbon, which undergoes nucleophilic attack by the active. site. serine oxygen (Fig. 2). The resulting carbamylatcd enzyme intermediate inhibits enzyme activity until a water molecule attacks the carbonyl carbon to reactivate enzyme and produce a carbamic acid derivative (Fig, 2). This rate of reactivation is considerably faster than that of phospylated enzyme, although it is not as rapid as reactivation of the acetylated intermediate. 

The cyclization of the imide ring is thought to be promoted by the acylation of the acid with another isocyanate group, forming the reactive mixed anhydride. The amide nitrogen can then easily cyclize by reaction with the activated carbonyl of the mixed anhydride, releasing the carbamic acid (Fig. 12.7). 

Isocyanates react with alcohols and phenols to form urethanes. In general, rates of urethane formation decrease in the following order primary alcohols > secondary alcohols > 2-alkoxyethanols > l-alkoxy-2-propanols. Isocyanates can react with urethanes to form allophanates. This reaction is much slower than the reaction of isocyanate with alcohol. Isocyanates react rapidly with primary and secondary amines to form ureas. The reaction is much faster than the reaction of isocyanates with alcohols. Isocyanates can react with ureas to form biurets. Biuret formation is slower than urethane formation, but faster than allophanate formation. Isocyanates react with water to form imstable carbamic acids, which dissociate into carbon dioxide and an amine. The amine is so much more reactive that it reacts with another isocyanate (in preference to water) to form mea. The reactivity of water with isocyanates is somewhat slower than that of secondary alcohols, but much more rapid than that of imcatalyzed reaction with methanes or ureas. 

The amino function is deprotected by hydrogenolysis (Section 22-2), which initially furnishes the carbamic acid as a reactive intermediate (Section 20-7). Decarboxylation occurs instantly to restore the free amine. 

---