Decarboxylation carbamic acid

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 chloride (60 1) and 2 volumes of water were mixed ready for subsequent addition of alkali to effect controlled hydrolysis. Before alkali was added, the internal temperature rose from 15 to 25° during 30 min, and then to 35°C in 5 min, when gas was suddenly evolved. This was attributed to the effect of liberated hydrochloric acid causing autocatalytic acceleration of the hydrolysis and then rapid release of carbon dioxide arising from decarboxylation of the carbamic acid. Hydrolysis by addition of the chloride to excess alkali would prevent the gas evolution. 

R-NH-COOH), followed by decarboxylation to the aromatic amine, was an important pathway in humans. However, in contrast to loratadine, the carbamic acid metabolite appeared to be sufficiently stable to be detectable in fair amounts in human urine. It can be postulated that the aromatic nature of the amine accounts for the relative stability of its carbamic acid derivative. 

H-1,3-Benzoxazine-2,4(3H)-dione (7.98) is an interesting cyclic carbamate. Hydrolysis of the ester group likely yields the ring-opened carbamic acid 7.99 as an undetected intermediate, which very rapidly decarboxylates to form the product salicylamide (7.100). When the cyclic carbamate was ad-... 

Cleavage of the carbon-nitrogen bond occurs in benzyloxycarbon amino compounds as a result of decarboxylation of the corresponding free carbamic acids resulting from hydrogenolysis of benzyl residues [725, 729, 7S0] (p. 151). 

Hydrolysis of the trimethylsilyl urethane (1 R=C02SiMe3), prepared by the action of trimethylsilyl iodide on the methyl carbamate (1 R = C02Me), with methanol at -78 °C yields the carbamic acid (1 R = C02H). On allowing a CDC13 solution of the carbamic acid to warm to room temperature, decarboxylation takes place to yield the deep red, highly unstable 1//-azepine (1 R=H) (80AG(E)1016>. 

Carbamates can be prepared by O-alkylation of carbamic acids R2N-CO2H. Carba-mic acids are usually susceptible to decarboxylation, but the corresponding salts can be prepared from amines and carbon dioxide under basic reaction conditions and... 

The newly-formed activated monomer then continues the chain process, and the decarboxylation of the carbamic acid produces the previous type of polypeptide but one unit longer. 

The carbamic acid decarboxylates and thus the above-given equilibrium would be displaced to the right. 

A foam is formed by addition of the proper amount of water. The water reacts with the isocyanate end groups to form carbamic acids which decarboxylate to give amine groups ... 

Generally, carbamic acids, RR NC02H, are elusive species due to their tendency to decarboxylate, thus giving back C02 and the amine. Their isolation has been... 

Carbamic esters also hydrolyze by ester/amide carbonyl chemistry (described above) to the corresponding carbamic acid followed by carbamic acid decarboxylation (Fig. 11). Carbamic esters are not particularly susceptible to oxidation. 

Reaction with water to the unstable carbamic acid derivative which will undergo spontaneous decarboxylation ... 

Reaction of carboxylic acids gives acyl azides, which rearrange to isocyanates, and these may be hydrolyzed to carbamic acid or solvolysed to carbamates. Decarboxylation leads to amines. 

Fig. 4.37. Three El eliminations in the deprotection of a protected tripeptide. For the sake of brevity, a single formula in the second row of the scheme shows how the three tert-Bu—0 bonds het-erolyze. Of course, they are activated and broken one after the other. In the deprotection of the tert-butylated lysine side chain, the leaving group is a carbamic acid. Carbamic acids decarboxylate spontaneously (Figure 8.3, 8.5 and 8.6), which explains the final transformation. The preparation of the protected tripeptide is shown in Figure 4.41.

The isocyanate can he isolated if the Curtius degradation is carried out in an inert solvent. The isocyanate also can be reacted with a heteroatom-nucleophile either subsequently or in situ. The heteroatom nucleophile adds to the C=N double bond of the isocyanate via the mechanism of Figure 8.12. In this way, the addition of water initially results in a carbamic acid. However, all carbamic acids are unstable and immediately decarboxylate to give amines (see Figure 8.5). Because of this consecutive reaction, the Curtius rearrangement represents a valuable amine synthesis. The amines formed contain one C atom less than the acyl azide substrates. It is due to this feature that one almost often refers to this reaction as Curtius degradation, not as Curtius rearrangement. 

When it is time to remove the benzyloxycarbonyl protective group, the compound is reacted with hydrogen in the presence of a catalyst. The cleavage of the benzyl group by hydrogenolysis (see Section 23.3) is followed by spontaneous decarboxylation of the carbamic acid. An example is provided by the following equation ... 

The amino group of the A-benzyloxycarbonyl derivative is protected as the amide half of a carbamate ester (a urethane, Section 21-16), which is more easily hydrolyzed than most other amides. In addition, the ester half of this urethane is a benzyl ester that undergoes hydrogenolysis. Catalytic hydrogenolysis of the A-benzyloxy carbonyl amino acid gives an unstable carbamic acid that quickly decarboxylates to give the deprotected amino acid. 

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