Carbamates, amino functionalization

Acylation. Reaction conditions employed to acylate an aminophenol (using acetic anhydride in alkaU or pyridine, acetyl chloride and pyridine in toluene, or ketene in ethanol) usually lead to involvement of the amino function. If an excess of reagent is used, however, especially with 2-aminophenol, 0,A/-diacylated products are formed. Aminophenol carboxylates (0-acylated aminophenols) normally are prepared by the reduction of the corresponding nitrophenyl carboxylates, which is of particular importance with the 4-aminophenol derivatives. A migration of the acyl group from the O to the N position is known to occur for some 2- and 4-aminophenol acylated products. Whereas ethyl 4-aminophenyl carbonate is relatively stable in dilute acid, the 2-derivative has been shown to rearrange slowly to give ethyl 2-hydroxyphenyl carbamate [35580-89-3] (26). 

The most important group of derivatives for the amino function (Fig. 7-4) is the carbamate group, which can be formed by reactions with acids, acid chlorides or acid anhydrides. A series of chlorides as 2-chloroisovalerylchloride [1], chrysanthe-moylchloride [2] and especially chloride compounds of terpene derivatives (cam-phanic acid chloride [3], camphor-10-sulfonyl chloride [4]) are used. The a-methoxy-a-trifluoromethylphenylacetic acid or the corresponding acid chloride introduced by Mosher in the 1970s are very useful reagents for the derivatization of amines and alcohols [5]. 

The synthetic potential of alkenylzirconium complexes is partially due to the fact that the hydrozirconation of alkynes can be carried out in the presence of some synthetically useful functional groups such as halide [80,153, 211, 212], acetals, amides, imides, carbamates, sulfides [186], ester, cyano [95, 213] and chiral propargyl amino functionalities [214]. 

In the reaction of an aminoalcohol with a methyl imidazole-AT-carboxylate or tert-butyl imidazole-AT-peroxycarboxylate, selective acylation of the amino function can be achieved11903 to give the carbamate and peroxycarbamate, respectively, the hydroxy groups of which can be further acylated ... 

The first manufacturing route of the GEM side-chain relied on a-cyanoketone 125 however, the number of chemical steps from 125 to the final side-chain was reduced by one step (Noh et ah, 2004a). The sequence began with a selective hydrogenation with Raney nickel followed by double bond migration to enamine 131 (Scheme 4.25). The amino functionality of 131 was then monoprotected, and the double bond was reduced under hydrogenation conditions to afford pyrrolidine-3-one 133. Treatment of 133 with methoxylamine yielded methoxyoxime 129. Deprotection of the carbamate functionality was achieved with methanesulfonic acid to afford the C7-side-chain as the bis-methansulfonate salt. 

Related methods may be used to introduce amino functions. For example, thiocyanate 237, made from the 4,6-dimesylate, rearranges to the isothiocyanate 238,225 and 3,4-unsaturated 2-cyanates, easily made in situ from the corresponding carbamates, afford the A-bonded 4-isocyanates of the 2-enes.229 From both types of rearranged products aminodeoxy sugars may be accessed, and in this way perosamine peracetate (239) can be synthesized from the cyanate of a 3,4-unsaturated 2-ol, which is thermally rearranged prior to dihydroxylation and acetylation.229... 

FIGURE 36.24 The amino functional group of L-dopa is linked to the phenolic function of entacapone by means of a carbonyl group thus a carbamate function links the two active agents. 

We developed a novel method allowing the preparation of highly strucmred and functionalized materials with amino functions by introducing transformable cores based on ionic interactions (ammonium carbamate salts) and van der Waals interactions. The CO2 uptake on the commercially available iV-(6-aminohexyl)-3-... 

Widely used protective groups for amino functions (see Section 4.3.2 Carbamates ), such as Z or Fmoc residues, are also employed for the protection of alcohol... 

Linker 31 was attached via a carbamate-ester to an amino-functionalized polymeric support (Fig. 7). Treatment with lithium hydroxide liberated linker acid 32. First attempts to use this enzyme cleavable linker on crosslinked... 

The tert-BOC and CBz functions have not yet found significant use in the protection of base amino functions. The only carbamate that has found extensive use is the isobutyloxycarbonyl function. This may be introduced by reaction of the nucleoside with isobutyryl chloroformate followed by deacylation of the sugar moiety ... 

The amino function is deprotected by hydrogenolysis (Section 22-2), which initially furnishes the carbamic acid as a reactive intermediate (Section 20-7). Decarboxylation occurs instantly to restore the free amine. 

Nicolaou et al. have prepared a library of 22 Sarcodictyin-analogs by attaching core structure 2 onto solid phase using polymer-bound Wittig-ylide 1 (Scheme 1) [74]. The OH-groups of the core scaffold were decorated by alkylation or converted to carboxylic acid or amino functionalities which could be derivatized as esters, carbamates, or secondary amines. Cleavage off the soUd phase was performed via trans-ketalization, a reaction step which was exploited to increase the diversity by using different kind of alcohols. 

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. 

C—X) for the application at hand. Benzyl trans-l,3-butadiene-l-carbamate has the amino group protected with the benzyloxycar-bonyl group. The ability to remove this functionality by catalytic... 

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