Benzyl ester cleaved

Deprotection by this method rests on the ease with which benzyl esters are cleaved by nucleophilic attack at the benzylic carbon m the presence of strong acids Bromide ion IS the nucleophile... 

A phenacyl ester is much more readily cleaved by nucleophiles than are othc esters such as the benzyl ester. Phenacyl esters are stable to acidic hydrolysis (e.g coned. HCh HBr/HOAc 50% CF3COOH/CH2Cl2 HF, 0°, 1 h ). 

The carboxamidomethyl ester was prepared for use in peptide synthesis. It is formed from the cesium salt of an A-protected amino acid and a-chloroacetamide (60-85% yield). It is cleaved with 0.5 M NaOH or NaHCOa in DMF/H2O. It is stable to the conditions required to remove BOC, Cbz, Fmoc, and r-butyl esters. It cannot be selectively cleaved in the presence of a benzyl ester of aspartic acid. ... 

Cycloalkyl esters have.been used to protect the /3-CO2H group in aspartyl peptides to minimize aspartimide formation during acidic or basic reactions. Aspartimide foimation is limited to 2-3% in TFA (20 h, 25°), 5-7% with HF at 0°, and 1.5-4% TfOH (thioanisole in TFA). Cycloalkyl esters are also stable to Et3N, whereas use of the benzyl ester leads to 25 % aspartimide formation during Et3N treatment. Cycloalkyl esters are stable to CF3COOH, but are readily cleaved with HF or TfOH. - ... 

The most useful property of benzyl esters is that they are readily cleaved by hy-drogenolysis. 

Catalytic transfer hydrogenation (entries 2 and 3 below) can be used to cleave benzyl esters in some compounds that contain sulfur, a poison for hydrogenolysis catalysts. 

Na, ammonia, 50% yield." These conditions were used to cleave the benzyl ester of an amino acid the Cbz and benzylsulfenamide derivatives were also cleaved. 

The p-bromobenzyl ester has been used to protect the /3-COOH group in aspartic acid. It is cleaved by strong acidic hydrolysis (HF, 0°, 10 min, 100% yield), but is stable to 50% CF3COOH/CH2CI2 used to cleave /-butyl carbamates. It is 5-7 times more stable than a benzyl ester. ... 

A benzyl ester can be cleaved in the presence of the 4-sulfobenzyl ester by CF3S03H. - ... 

The protective group is removed by mildly alkaline conditions that do not cleave methyl or benzyl esters. The group is stable to CF3COOH, HCl-AcOH, and HBr-AcOH. A polymer-bound version of this group has also been developed. ... 

Electrolysis —2.9 V, DMF, R4N X , 70-80% yield or Pd/graphite cathode, MeOH, AcOH, 2.5% NaCl04 (0.5 mol/L), 99% yield.Benzyl ethers and tosylates are stable to these conditions, but benzyl esters are cleaved. 

Catecholborane halide cleaves benzyl carbamatesi in the presence of ethyl and benzyl esters and TBDMS ethers." ... 

Catalytic hydrogenolysis of an O-benzyl protective group is a mild, selective method introduced by Bergmann and Zervas to cleave a benzyl carbamate (>NC0-0CH2C6H5 —> >NH) prepared to protect an amino group during peptide syntheses. The method has also been used to cleave alkyl benzyl ethers, stable compounds prepared to protect alkyl alcohols benzyl esters are cleaved by catalytic hydrogenolysis under neutral conditions. 

In a penicillin synthesis, the carboxyl group was protected as a / -bromophenacyl ester that was cleaved by nucleophilic displacement (PhSK, DMF, 20°, 30 min, 64% yield). Hydrogenolysis of a benzyl ester was difficult (perhaps because of catalyst poisoning by sulfur) basic hydrolysis of methyl or ethyl esters led to attack at the /3-lactam ring. ... 

Formation of this ester proceeds under standard DCC coupling conditions (DMAP, THF, 28-93%). The ester is cleaved with 1% TFA or dichloroacetic acid in CH2CI2 by DDQ (reflux, CH2CI2, H2O, 5-15 h, 47-92% yield). Hydrogenolysis (Pd/C, EtOAc, MeOH) cleaves the ester in 23 h, whereas a benzyl ester is cleaved in 10 min under these conditions. ... 

TiCl4, Mg-Hg, THF, 40-70% yield. Benzyl esters are also cleaved. 

NBS, CCI4, BZ2O, reflux, 61-97% yield. Substituted benzyl esters are cleaved similarly. 

Benzyl esters of carboxylic acids are frequently used in organic synthesis for the protection of carboxyl groups. The C-O bond in benzyl esters can be cleaved more easily than the corresponding benzyl ether bond. The hydrogenolysis of an ester leads to carboxylic acid and toluene. Examples of debenzylation of benzyl esters of carboxylic acids on Pd/C catalysts are summarized in Table 4.4. 

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