Aryl carbamates

Alcohols and phenols can be attached to support-bound alcohol linkers as carbonates [467,665,666], although few examples of this have been reported. For the preparation of carbonates, the support-bound alcohol needs to be converted into a reactive carbonic acid derivative by reaction with phosgene or a synthetic equivalent thereof, e.g. disuccinimidyl carbonate [665], carbonyl diimidazole [157], or 4-nitrophenyl chloro-formate [467] (see Section 14.7). The best results are usually obtained with support-bound chloroformates. The resulting intermediate is then treated with an alcohol and a base (DIPEA, DMAP, or DBU), which furnishes the unsymmetrical carbonate. Carbonates are generally more resistant towards nucleophilic cleavage than esters, but are less stable than carbamates. Aryl carbonates are easily cleaved by nucleophiles and are therefore of limited utility as linkers for phenols. 

Hiyama Cross-couplings. Organosilanes undergo crosscoupling reactions with both primary and secondary alkyl bromides or iodides. Trifluorosilanes are converted to the corresponding products using a nickel/bathophenanthroline catalytic system (eq 7). Moreover, the reaction is compatible with functionalities such as ketones, carbamates, aryl and alkyl chlorides, lactones, acetals, and nitriles. ... 

The reaction is applicable to the preparation of amines from amides of aliphatic aromatic, aryl-aliphatic and heterocyclic acids. A further example is given in Section IV,170 in connexion with the preparation of anthranilic acid from phthal-imide. It may be mentioned that for aliphatic monoamides containing more than eight carbon atoms aqueous alkaline hypohalite gives poor yields of the amines. Good results are obtained by treatment of the amide (C > 8) in methanol with sodium methoxide and bromine, followed by hydrolysis of the resulting N-alkyl methyl carbamate ... 

Allylic acetates are widely used. The oxidative addition of allylic acetates to Pd(0) is reversible, and their reaction must be carried out in the presence of bases. An important improvement in 7r-allylpalladium chemistry has been achieved by the introduction of allylic carbonates. Carbonates are highly reactive. More importantly, their reactions can be carried out under neutral con-ditions[13,14]. Also reactions of allylic carbamates[14], allyl aryl ethers[6,15], and vinyl epoxides[16,17] proceed under neutral conditions without addition of bases. 

Esters Saturated Aryl and a,/3-unsaturated Diesters Oxalates Phthalates C=C—CO—o— Carbamates 1741-1725 1727-1714 1763-1761 1738-1728 1716-1708 1694-1688 Alkyl branching on carbon adjacent to C=0 lowers frequency by 5-15 cm k... 

Naphthol is mainly used in the manufacture of the insecticide carbaryl (59), l-naphthyl A/-methyicarbamate/ iJ-2j5 - (Sevin) (22), which is produced by the reaction of 1-naphthol with methyl isocyanate. Methyl isocyanate is usually prepared by treating methylamine with phosgene. Methyl isocyanate is a very toxic Hquid, boiling at 38°C, and should not be stored for long periods of time (Bhopal accident, India). India has developed a process for the preparation of aryl esters of A/-alkyl carbamic acids. Thus l-naphthyl methylcarbamate is prepared by refluxing 1-naphthol with ethyl methylcarbamate and POCl in toluene (60). In 1992, carbaryl production totaled > 11.4 x 10 t(35). Rhc ne-Poulenc, at its Institute, W. Va., facihty is the only carbaryl producer in United States. 

Me3SiI, CH3CN, 25-50°, 100% yield. Selective removal of protective groups is possible with this reagent since a carbamate, =NCOOCMe3, is cleaved in 6 min at 25° an aryl benzyl ether is cleaved in 100% yield, with no formation of 3-benzyltyrosine, in 1 h at 50°, at which time a methyl ester begins to be cleaved. 

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. 

To minimize racemization, the use of nonpolar solvents, a minimum of base, low reaction temperatures, and carbamate protective groups (R = O-alkyl or O-aryl) is effective. (A carbamate, R = O-r-Bu, has been reported to form an oxazolone that appears not to racemize during base-catalyzed coupling.) ... 

The potential for use of chiral natural materials such as cellulose for separation of enantiomers has long been recognized, but development of efficient materials occurred relatively recently. Several acylated derivatives of cellulose are effective chiral stationary phases. Benzoate esters and aryl carbamates are particularly useful. These materials are commercially available on a silica support and imder the trademark Chiralcel. Figure 2.4 shows the resolution of y-phenyl-y-butyrolactone with the use of acetylated cellulose as the adsorbent material. 

Na2C03, H2O, dioxane, warm, 97% yield. Phenols can be protected under similar conditions. Amines are converted by these conditions to carbamates that are stable to alkaline hydrolysis with sodium carbonate. Carbamates are cleaved by acidic hydrolysis (HBr, MeOH, CH2CI2, 8 h), conditions that do not cleave alkyl or aryl vinyl carbonates. 

Methylsulfinylbenzyl, 282 2,4-Dimethylpent-3-yl, 282 2,2,2-Trichloroethyl, 282 Vinyl, 282 Benzyl, 283 Aryl Carbamates, 283... 

When cysteine reacts with an alkyl or aryl chloroformate, both the -SH and -NH groups are protected, as a thiocarbonate and as a carbamate, respectively. Selective or simultaneous removal of the protective groups is possible. (See cleavage conditions 3-6 for an S-benzyloxycarbonyl derivative, page 485.)... 

Carbamates can be used as protective groups for amino acids to minimize racem-ization in peptide synthesis. Racemization occurs during the base-catalyzed coupling reaction of an A-protected, carboxyl-activated amino acid and takes place in the intermediate oxazolone that forms readily from an A-acyl-protected amino acid (R = alkyl, aryl) ... 

To minimize racemization, the use of nonpolar solvents, a minimum of base, low-reaction temperatures, and carbamate protective groups (R = O-alkyl or O-aryl) are effective. 

If R2 contains an a-hydrogen the method cannot be applied as enaminc formation occurs. Bisamides (or -carbamates) are often used in amidoalkylations of aryl and reactive methylene compounds, but the rather harsh reaction conditions severely limit application in the synthesis of more complicated molecules with other functional groups. 

PREPARATION OF N-ARYL-5R-HYDROXYMETHYL-2-OXAZOLIDINONES FROM N-ARYL CARBAMATES N-PHENYL-(5R)-HYDROXYMETHYL- 2-OXAZOLIDINONE... 

In the special case of alkaline hydrolysis of N-substituted aryl carbamates, there is another mechanism involving elimination-addition ... 

This mechanism does not apply to unsubstituted or N,N-disubstituted aryl carbamates, which hydrolyze by the normal mechanisms. Carboxylic esters substituted in the a position by an electron-withdrawing group (e.g., CN or COOEt) can also hydrolyze by a similar mechanism involving a ketene intermediate. These elimination-addition mechanisms usually are referred to as ElcB mechanisms, because that is the name given to the elimination portion of the mechanism (p. 1308). 

RNH2 (R=alkyl, but not aryl) are phenyliodosyl bis(trifluoroacetate), Phl(0-C0CF3)2 and hydroxy(tosyloxy)iodobenzene, PhI(OH)OTs. A mixture of NBS, Hg(OAc)2, and R OH is one of several reagent mixtures that convert an amide (RCONH2) to the carbamate (RNHCOOR ) (R=primary, secondary, or tertiary... 

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