Sensitivity toward amines

Tlie isolable dithiiranes (4 and 7) are fairly stable under acidic conditions but quickly lose a sulfur atom to give the corresponding thioketones under basic conditions (97BCJ509). Tliey are quite sensitive toward amines and phosphines. Oxidation with MCPBA gave the corresponding dithiirane 1-oxides in high yields. 

All the above-mentioned initiators are very sensitive towards substances with active hydrogen. Care must therefore be taken to exclude acids, water, thiols, amines, and acetylene derivatives. Oxygen, carbon dioxide, carbon monoxide, carbonyl compounds, and alkyl halides which can react with the initiator, also interfere with the reaction. Careful purification and drying of the starting materials and apparatus is, therefore, absolutely essential, especially when dealing with living polymers (see Example 3-19). 

Carboxylic acids can also be attached to solid supports as amides, imides, and thiol esters. Illustrative examples of the saponification of such linkers are listed in Table 3.5. Thiol esters are more sensitive towards nucleophilic attack than the corresponding esters, and can be readily saponified. Resin-bound thiol esters have, however, mainly been used for the preparation of amides by nucleophilic cleavage with amines (see Section 3.3.3). 

Aromatic and heteroaromatic amines can be linked to insoluble supports using strategies similar to those used for aliphatic amines. Because of the lower basicities of aromatic amines, however, their /V-bcnzyl derivatives will usually be more susceptible to acidolytic cleavage than aliphatic /V-bcnzylamincs. For the same reason, N-acyl derivatives of aromatic amines will generally be more sensitive towards nucleophiles than the corresponding derivatives of aliphatic amines. 

Phthalimide protection is stable towards acids and bases, but can be cleaved with strong nucleophiles, such as hydrazines or sulfides, or by reduction with sodium boro-hydride [230]. More sensitive towards nucleophilic attack than unsubstituted phthalimide is tetrachlorophthalimide [33]. This group has been successfully used as N(a) protection of amino acids in the solid-phase synthesis of peptides (deprotection N2H4/DMF (15 85), 40 °C, 1 h coupling DIC/HOAt/amino acid (1 1 1), 3 equiv. of each, DMF, 25 °C, 4 h [294]). Typical conditions for the removal of phthaloyl protection on cross-linked polystyrene include treatment of the resin with hydrazine hydrate [295,296], with methyl hydrazine [297], or with primary aliphatic amines [298] in DMF, EtOH, or solvent mixtures for several hours at room temperature or above [296,299,300]. Illustrative examples are sketched in Figure 10.15. It has been claimed that the hydrazinolysis of polystyrene-bound phthalimides proceeds more readily in DCM or DCE than in DMF [301]. 

The complexity of the base catalysis and its sensitivity towards extremely small quantities of impurities (25,67) e. g. water, amines, alcohols, caused a lot of mistakes in the previous experimental work and the... 

Used to derivatize primary amines to yield isothiocyanates Used for derivatization of tripeptides provides high sensitivity toward spectrofluorimetric detection... 

Asparagine is unique as an acceptor amino acid for ADP-ribosylation by C3-like transferases (Sekine et ai, 1989). In contrast, pertussis toxin modifies cysteine residues, and cholera toxin and C. botulinum C2 toxin specifically ADP-ribosylate arginine residues (for details see the relevant chapters). The ADP-ribose-asparagine bond formed by C3-like transferases is stable towards neutral hydroxyl-amine [0.5 M, 2h) and mercury ions (2m/Vl, 1 h), whereas cysteine and arginine-specific ADP-ribosylation, respectively, are sensitive towards these agents (Aktories ef a/., 1988a). 

General note The cumulenic amine is extremely sensitive towards oxygen. Traces of oxygen cause a rapid increase of the viscosity and a darkening of the colour. If treated carefully, the compound remains unchanged during storage at —20 °C for a limited period. 

Methods of Preparation. Primary nitramines cannot be prepared by the direct nitration of primary amines. Because of their sensitivity toward acid, they probably do not survive in the strongly acidic environment of the nitration. They are generally made by alkaline hydrolysis of nitramides. 

Trifluoromethylphenyl)sulfonylethoxy-carbonyl group (Tsc), 2-(4-trifluoromethyl-phenylsulfonyl)ethoxycarbonyl, a base-labile protection group for amines, especially suited for the heteroaromatic pyrrole and imidazole amino acids Trp and His. The Tsc group differs from the 9-fiuorenylmethoxycarbonyl (Fmoc) group in decreased sensitivity toward premature cleavage [J. S. Choi et al., Tetrahedron 2005, 61, 2493]. 

DCA is a baseline toxicant in algae and fish but specifically toxic in Daph-nia magna. Ur restar azu-Ramos et al. [46] compared the sensitivity towards different aromatic amines between different aquatic species and concluded that water fleas are consistently more sensitive than other aquatic species. However, they could not resolve the underlying mechanism. 

Derivatization with acetic anhydride increases the sensitivity towards the secondary amines of the group and the hydroxylated phencyclidine metabolites. The esters and amides so formed are listed in Table 8-20 below. 

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