Carbamic acid intermediates

Industrially, polyurethane flexible foam manufacturers combine a version of the carbamate-forming reaction and the amine—isocyanate reaction to provide both density reduction and elastic modulus increases. The overall scheme involves the reaction of one mole of water with one mole of isocyanate to produce a carbamic acid intermediate. The carbamic acid intermediate spontaneously loses carbon dioxide to yield a primary amine which reacts with a second mole of isocyanate to yield a substituted urea. 

The deprotection of the Cbz protected amino acid proceeds via a two step mechanism (Figure 1). The first step comprises the catalytic hydrogenolysis of the benzyloxy group of the Cbz-protected amino acid (1). Toluene (3) is formed from the O-benzyl group as well as an unstable carbamic acid intermediate (2). This intermediate decomposes to form the unprotected amino acid (4) and carbon dioxide (5). 

The removal of a carbobenzyloxy group can be separated into two steps (Figure 1). The first step comprises the hydrogenolysis of the benzyl oxygen bond of the Cbz-protected amino acid 1 to form a carbamic acid intermediate 2 and toluene 3. The carbamic acid intermediate decaiboxylates to give the deprotected amino acid 4 and one equivalent of carbon dioxide 5. 

Dinsmore and Mercer further investigated this reaction using DBU as a base and n-Bu3P/DBAD (di-tert-butyl azodicarboxylate) as Mitsunobu s reactants, and found an unexpected steroselectivity in the Mitsunobu transformation [75b], In fact, the stereochemical course of the Mitsunobu reaction (Scheme 6.11) depended on whether the carbamic acid intermediate was N-substituted with hydrogen (retention) or with carbon (inversion). 

Thiocyanates are converted to thiocarbamates in a similar reaction R—S—C=N + H2O R S C O NH2. Hydrolysis of cyanamides gives amines, produced by the breakdown of the unstable carbamic acid intermediates R2NCN [R2NCOOH] R2NH. 

It has been reported by Bailey [25] that use of a high concentration of aliphatic tertiary base at low temperatures enables the controlled addition of single amino acid residues to peptide amine end-groups to be achieved by reaction with an NCA. The success of this procedure depends on the quantitative formation of a trialkylammonium carbamate (XXX) by interaction of the carbamic acid intermediate in reaction (9a) with the tertiary base the over-all reaction is shown in (51)... 

Several different kinds of polyurethanes are produced, depending on the nature of the polymeric alcohol used. One major use of polyurethane is in the stretchable spandex fibers used for bathing suits and leotards. These polyurethanes have a fairly low degree of cross-linking so that the resultant polymer is soft and elastic. A second major use of polyurethanes is in the foams used for insulation. Foaming occurs when a small amount of water is added during polymerization, giving a carbamic acid intermediate that spontaneously loses bubbles of COj. 

CSI (57) can also be used to obtain N,N-disubstituted sulfamides (145) by treatment with pentachlorophenol. This reaction gives the vsulfamide (146) via the unstable carbamic acid intermediate (147). On heating with a secondary amine, (146) affords a good yield of the corresponding N,N-dialkylsulfamide (145). The final step involves elimination of the pentachlorophenoxy anion, which is an excellent leaving group (Scheme 59). 

This last reaction, the hydrolysis of coordinated nitriles, has been extensively studied by Ford and co-workers acidic hydrolysis of [Rh(NH3)5NCO] has been used as an alternate route to the hexaammine (equation 113). The reaction was shown to go through a carbamic acid intermediate, which was isolated and characterized. The kinetic study of the hexaammine formation was complicated by the presence of these two consecutive reactions, and by two different reaction paths. The mechanism proposed for the hydrolysis of the coordinated cyanate is shown in Scheme 14 at low acid concentrations (0.005 to 0.025 M) the rate determining step is HjO attack of the protonated species leading to a rate expression which is first-order in [H ] rate = ky [RhlfH" ]. At higher acid concentrations (0.2 to 1.0 M), decomposition of the carbamic acid complex is rate determining, and... 

Reaction with water produces an amine and carbon dioxide through an unstable carbamic acid intermediate (Scheme 3.22). 

The Boc group is very sensitive to acid. Treating the Boc derivative of an amino acid with trifluoroace-tic acid leads to a carbamic acid intermediate that decarboxylates. The rcrt-butyl group is converted to 2-methylpropene (isobutylene) in the decarboxylation reaction. 

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