Trichlorophenyl carbonate

Historically, the first practicable reagent for the synthesis of N -Boc amino acids, tert-butyl 4-nitrophenyl carbonate (52), was developed by Anderson and McGregorb (Scheme 25). Due to the low reactivity of this mixed carbonate, drastic reaction conditions are required and yields remain unsatisfactory because of the difficult and laborious separation of the byproduct 4-nitrophenol. Alternative mixed carbonates have been proposed such as tert-butyl 2,4,5-trichlorophenyl carbonate (53),b32] lert-butyl pentachlorophenyl carbonate (54),b33] tert-butyl 2-pyridyl carbonate (55)0-tert-hvXy 5-4,6-dimethylpyrimidin-2-yl thiocarbonate (56).b3 1 With the latter two reagents the byproducts, pyridin-2-ol and 4,6-dimethylpyrimidine-2-thiol, respectively, are acid soluble and, thus, readily removed. 

Peptide synthesis /-Amyl chloroformate. Bis-(2,4-dinitrophenyl)carbonate. Bis-o-phenylene pyrophosphite. i-Butyl chloroformate. sec-Butyl chloroformate. /-Butyl chloroformate. /-Butyl 2,4,5-trichlorophenyl carbonate. CopoIy(ethylene-N-hydroxymaleimide). N,N-Diethyl-I-propynylamine. Di-(p-nitrophenyl)sulfate. Ethoxyacetylene. N-Ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline. N-Ethylbenzisoxazolium fluoroborate. Ethyl chloroformate. N-Ethyl-5-phenylisoxazolium-3 -sulfonate. N-Hydroxysuccinimide trifluoroacetate. Methyl-morpholine. 4-Methylthiophenol. p-Nitrophenol. Oxalylchloride. Pentachlorophenol. Pentamethylbenzyl chloride. /-Pentyl chloroformate. Phenacyl bromide. Polyhexamethylene carbodiimide. Tetraethyl pyrophosphite. 1,2,4-Triazole. 

Peptide synthesis, N-protection Acetic-formic anhydride. Adamantyl chloroformate. Benzylthiocarbonyl chloride. /-Butoxycarbonyl-N-hydroxysuccinimide ester. /-Butyl azido-formate. /-Butylcarbonic diethylphosphoric anhydride. /-Butyl fluoroformate. /-Butyl oxycarbonyl fluoride. /-Butyl pentachlorophenyl carbonate. /-Butyl 2,4,5-trichlorophenyl carbonate. Carbobenzoxy chloride. 3,5-Dimethoxybenzyl p-nitrophenyl carbonate. [2-(Diphenyl)isopropyljphenyl carbonate. /-Pentyl chloroformate. 

Fig. 2 Examples of activated PEG molecules reactive towards amino groups a PEG succin-imidyl succinate, B PEG succinimidyl carbonate, C PEG p-nitrophenyl carbonate, D PEG benzotriazol carbonate, E PEG trichlorophenyl carbonate, F PEG carbonylimidazole, G PEG tresylate, and h PEG dichlorotriazine...

Figure 3 Acylating PEGs (8) PEG 2,5-dioxocyclopentyl succinates (9) PEG succinimidyl carbonate (10) PEG 4-nitrophenyl carbonate (11) PEG 2,4,5-trichlorophenyl carbonate and (12) PEG imidazol-1-yl carbonate.

One-step proeess. A soln. of benzyl p-nitrophenyl carbonate in dioxane added to aq. Na-glycinate (prepared from glycine and NaHGOg) heated 3 hrs. at 100°, 1 N HGl added in the cold followed by a soln. of dicyclohexylcarbodiimide in dioxane, kept 0.5 hr. in an ice-bath, and 2 hrs. at room temp. benzyloxy-carbonylglycine p-nitrophenyl ester. Y 78%. F. e. s. Y. Wolman, D. Ladkany, and M. Frankel, Soc. (G) 1967, 689 with ferf-butyl 2,4,5-trichlorophenyl carbonate, co-extraction of the intermediates, cf. W. Broadbent, J. S. Morley, and B. E. Stone, Soc. (G) 1967, 2632 with ferf-butyl pentachlorophenyl carbonate cf. M. Fujino and G. Hatanaka, Ghem. Pharm. Bull. 15, 2015 (1967). 

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