Deblocking reaction

Stop the deblocking reaction by the addition of NaOH to raise the pH back to neutrality. 

Some tellurium anionic reagents offer a great contribution to these deblocking reactions owing to the use of mild experimental conditions and a non-hydrolytic medium. 

Protection of carboxyl groups. The deblocking reaction discussed above with 2 is also applicable to a halogenated protected derivative of the terminal carboxyl group of peptides. The N-protected amino acid is converted by the Passerini reaction with an o-halo aldehyde into a protected derivative such as 4. The derivative is cleaved by reiietion with 2 at 20° in acetonitrile or methanol (equation III). 

Zemplen deacylation is the most commonly used deblocking reaction for the removal of ester protecting groups [220]. Using this transesterification reaction, OH-functions can be regenerated under mild conditions, in methanol with a catalytic amount of sodium methoxide at room temperature. The difference in the rate of benzoate and acetate solvolysis is sufficient to enable removal of acetates in the presence of benzoates. Typical conditions for this selective cleavage include ammonia in MeOH. 

Catalysis plays an important role in the deblocking or thermal dissociation of the blocked isocyanates. Notably organometallie compounds and tertiary amines are capable of lowering both the deblocking temperature and time as compared to the uncatalyzed systems. Wicks (61) has pointed out that since most of the deblocking reactions are carried out in the presence of hydroxyl... 

Although the theoretical rate equations indicate that a higher concentration leads to a faster reaction, there are some practical limits to reactant concentration. The solubility of the reactant in the synthesis solvent restricts the upper limit of the concentration. There is also the possibility of the occurrence of undesired side reactions with highly concentrated or reactive reagents. This is particularly true for the deblock reaction. For instance, when higher concentrations of acid are used in the deblock reaction in oligonu-... 

Equation (1) for the deblock reaction indicates that the formation of the product (B) is equal to the liberation of the protecting group (E). If the accumulation of the protecting group can be monitored, then the extent of the reaction can be determined. 

The detector output for the deblock reaction can be a useful tool for identifying slow reactions or gross coupling failures. Because of the inherent inaccuracies, it should not be used to measure the absolute success of the synthesis or to replace other analytical techniques (e.g., HPLC, MS) (see... 

Normalized absorbance curves for the absorbances at 1738 cm and 2256 cm" (Figure 11) reveal that the deblocking reaction begins near 120 C and ends at approximately 200 C. Figure 12 shows percent conversion as a function of temperature for the experimental data and the conversion curves calculated from the experimentally determined kinetic parameters. The excellent fit between the experimental and calculated curves shown in Figure 12 demonstrates that the kinetics parameters determineu from the appearance of isocyanate functionality accurately describe the thermal dissociation of the blocked IPDI. 

This deblocking reaction is accelerated by certain catalysts and by the presence of a polyol which can compete with the caprolactam for the NCO group via a transesterification type reaction. The blocking of the isocyanate group allows lEM-containing polymers to be formulated with polyols to give room temperature-stable formulations which deblock and cross-link at higher temperatures. 

Photosensitive blocking groups may afford mild deblocking reactions if the groups are sensitive at wavelengths at which proteins are stable. 

Indeed, at temperatures exceeding 160 °C, the deblocking reaction takes place, resulting in free isocyanate groups that can react with an amide functionality in the polymer chain to form a branch point (Scheme 23). Although these types of reactions occur for both mono- and difunctional carbamoyl-CL activators, the effect is more significant with difunctional activators owing to the fact that all chain ends remain active after... 

Scheme 23 Deblocking reaction and branch point formation.

Because of the particular sensitivity of glycopeptides, precautions must be taken during the assembly of the target molecule, in particular during the deblocking reactions. 

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