T-BUTYL AZIDOFORMATE

The /-butoxycarbonyl group (Boc, "t-box ) has been eMens vely used in peptide synthesis, and Boc derivatives of many amino acids are commercially available. The customary reagent for the preparation from the amine is t-butyl azidoformate in water, dioxane/water, DMSO, or DMF. The cleavage by acids of medium strength proceeds with concomitant loss of isobutene and carbon dioxide (L.A. Carpino, 1957, 1973 see section 4.1.2.2). 

Certain preparations—mesitoic acid, 7-t-butoxynorbornadi-ene, cyclopentanecarboxaldehyde, t-butyl azidoformate, indole-... 

The reagent is prepared1 in 80% yield by the reaction of 1-trimethylsilyltriazole-1,2,42 with t-butyl azidoformate (1, 84-85 2, 44 45 this volume). 

AMINO GROUPS 5-Benzisoxazolemethylylene chloroformate. t-Butyl azidoformate. 

The instability of /er/-butyl chloroformate limits its use for preparing Boc derivatives. rm-Butyl fluoroformate (bp 40-42 C/23.3 kPa) is more stable than the chloro derivative and more reactive than /err-butyl azidoformate (HAZARD). Both reagents should be prepared afresh. re/t-Butyl azidoformate (bp 36.5-37.5 C/1.3 kPa) has the added frisson of being explosive hence, it should be prepared in situ from the reaction of Boc-hydrazide with nitrous acid and used without purification. Moreover, the by-product of aqueous workup, hydrazoic acid, is highly toxic. 

R = H, = Me) and (96 R = Me, R = H) is obtained by oxidative decarboxylation of the bicyclo[4.1.0]hept-3-ene-l,6-dicarboxylic acid (95) with lead tetra-acetate. The amino-acid (97), prepared from C- (o-hydroxyphenyl)glycine and t-butyl azidoformate, cyclizes to the aminobenzofuranone (98) this type of product exhibits chemiluminescence when exposed to oxygen in the presence of a base. Treatment of 2,2 -di(bromomethyl)benzil (99) with potassium t-butoxide results in an unusual intramolecular nucleophilic substitution to give the spiro-compound (100). 

Although t-butyl azidoformate [373-375], t-butyl p-nitrophenyl carbonate [376], and f-butyl cyanoformate [375] have been recommended as t-butoxycarbonylating reagents, these cannot be synthesized as easily as benzyloxycarbonyl chloride. 

Related Reagents. 7V-(r-Butoxycarbonyloxy)phthalimide N-(r-Butoxycarbonyloxy)succinimide t-Butyl Azidoformate t-Butyl Chloroformate Di-r-butyl Dicarbonate. 

Related Reagents. Allyl Chloroformate Benzyl Chlo-roformate 4-Bromobenzyl Chloroformate t-Butyl Azidoformate l-(t-Butoxycarbonyl)-lEf-benzotriazole 3-A-oxide 1 -(r-Butoxycarbonyl)imidazole 2-(t-Butoxycarbonyloxyimino)-2-phenylacetonitrile A-(t-Butoxycarbonyloxy)phthalimide A-(t-Butoxycarbonyloxy)succinimide V-(r-Butoxycarbonyl)-1,2,4-triazole Di-t-butyl Dicarbonate Ethyl Chloroformate 9-Fluorenylmethyl Chloroformate Isobutyl Chloroformate Methyl Chloroformate 2,2,2-Tribromoethyl Chloroformate 2,2,2-Trichloroethyl Chloroformate 2,2,2-Trichloro-t-butoxycarbonyl Chloride 2-(Trimethylsilyl)ethyl Chloroformate Vinyl Chloroformate. 

Related Reagents. t-Butyl Azidoformate f-Butyl Chloro-formate l-A(-(t-Butoxycarbonyl)-l//-benzotriazole 3-A-Oxide 1 -(t-Butoxycarbonyl)imidazole 2-(t-Butoxycarbonyloxyimino)-2-phenylacetonitrile A/ -(t-Butoxycarbonyloxy)phthalimide N-(7-Butoxycarbonyloxy)succinimide 1-r-Butoxycarbonyl-1,2,4-tri azole. 

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