Carbamates cleavage

Some heterocycles can be linked to supports as tetrahydropyranyl derivatives. Attachment of indoles, purines, or tetrazoles (Table 3.29) has been achieved by treatment of a support-bound dihydropyran with the heterocycle in the presence of catalytic amounts of pyridinium tosylate [487], camphorsulfonic acid [539], or TFA [540] in DCE at 60-80 °C for 16-24 h. Indole-derived orthoesters, such as that in Entry 7 (Table 3.29), can be prepared by heating the indole with triethyl orthoformate (160 °C, 24 h) followed by acid-catalyzed reaction of the resulting orthoester with a resin-bound diol [541,542], As illustrated by Entry 8 (Table 3.29), indoles can also be linked to the Wang resin or related supports as carbamates. Cleavage by TFA is, how-... 

In plants, EPTC was hypothesized to undergo hydroxylation at the carbon alpha to the sulfur, followed by carbamate cleavage... 

The carbolithiation- N C aryl migration sequence was performed in TH F, with and without the addition of DMPU, followed by the carbamate cleavage leading to highly substituted propargyl alcohols 47. When the enyne 48 was treated with n-BuLi in toluene without the addition of DMPU, allene products were observed after the protonation step (Scheme 10.16). The addition of (—)-sparteine and carrying out the reaction at —78 °C led to the product 49 as a racemic mixture or at best with moderate enantiomeric excess. 

Figure 8.5 Drug release mechanism from polyurethane carriers. PU-ester carriers undergo relatively faster burst ester hydrolysis followed by slow carbamate cleavage. The release may be controlled by tuning the esterxarbamate ratio.

This approach is compHcated by the fact that the isocyanate is produced via the thermolytic cleavage of the methyl carbamate. Reactions with the unconverted carbamate caimot be prevented. Much effort has been focused on improving the selectivity of the latter step. 

JUNG OLAH - VORONKOV Etherdeavage Cleavage of ethers or esters, carbamates, phosphorates with trimethylsilyl Iodides. Oeoxygenation of sulfoxides. 

Zn, THF-H2O, pH 4.2, 25°, 4 h. The authors suggest that selective cleavage should be possible by this method since at pH 4.2, 25°, 2,2,2-trichlo-roethyl esters are cleaved in 10 min, 2,2,2-trichloroethyl carbamates are cleaved in 30 min, and the 2,2,2-trichloroethyl carbonate of estrone, formed in 87% yield from estrone and the acid chloride, is cleaved in 4 h (97% yield). 

H2/Pd-C, EtOH, 20°. < -Bromobenzyl carbonates have been developed for use in solid-phase peptide synthesis. An aryl o-bromobenzyl carbonate is stable to acidic cleavage (CF3CO2H) of a /-butyl carbamate a benzyl carbonate is cleaved. 

Comparison of Cleavage Rates for Various Carbamate Proi ctive Groups... 

Alkyldithio carbamates are prepared from the acid chloride (Et N, EtOAc, 0°) and amino acid, either free or as the O-silyl derivatives (70-88% yield). The N- i-propyldithio) carbamate has been used in the protection of proline during peptide synthesis. Alkyldithio carbamates can be cleaved with thiols, NaOH, Ph P/TsOH. They are stable to acid. Cleavage rates are a function of the size of the alkyl group as illustrated in the table below. 

The Moz group is more readily cleaved by acid than is the benzyloxycarbonyl or BOC group.The section on benzyl carbamates should be consulted since many of the methods for formation and cleavage should be applicable to the Moz group as well. 

H2/Pd-C, 10 h, 87% yield. A nitrobenzyl carbamate is more readily cleaved by hydrogenolysis than a benzyl carbamate it is more stable to acid-catalyzed hydrolysis than is a benzyl carbamate, and therefore selective cleavage is possible. 

Cyclobutyl Carbamate (Chart 8). The half-life for cleavage in neat CF3CO2H is > 300 min. 

Protective group chemistry for these amines has been separated from the simple amines because chemically they behave quite differently with respect to protective group cleavage. The increased acidity of these aromatic amines makes it easier to cleave the various amide, carbamate, and sulfonamide groups that are used to protect this class. A similar situation arises in the deprotection of nucleoside bases (e.g., the isobutanamide is cleaved with methanolic ammonia ), again, because of the increased acidity of the NH group. 

Trichloroethyl Carbamate (Troc-NR2) R2NCO2CH2CCI3 Formation/Cleavage ... 

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