Of carbamates esters

Fig. 7.3. Hydrolysis of carbamate esters (7.2) to carbamic acid (7.3), and spontaneous breakdown of the latter...

Intermolecular alcoholysis of carbamate esters will also take place, but the reactions are very slow. In comparison with intermolecular nucleophilic attack by a phenoxide ion of the same on the unsubstituted ester [28], the effective molarity of the neighbouring phenoxide ion of [27] is 3 x 10 M. Thus, a phenoxide ion is an... 

Aluminum porphyrins with alkoxide, carboxylate, or enolate can also activate CO2, some catalytically. For example, Al(TPP)OMe (prepared from Al(TPP)Et with methanol) can bring about the catalytic formation of cyclic carbonate or polycarbonate from CO2 and epoxide [Eq. (6)], ° - and Al(TPP)OAc catalyzes the formation of carbamic esters from CO2, dialkylamines, and epoxide. Neither of the reactions requires activation by visible light, in contrast to the reactions involving the alkylaluminum precursors. Another key difference is that the ethyl group in Al(TPP)Et remains in the propionate product after CO2 insertion, whereas the methoxide or acetate precursors in the other reactions do not, indicating that quite different mechanisms are possibly operating in these processes. Most of this chemistry has been followed via spectroscopic (IR and H NMR) observation of the aluminum porphyrin species, and by organic product analysis, and relatively little is known about the details of the CO2 activation steps. 

The most common industrial syntheses of carbamate esters are based on either the alcoholysis of phosgene, followed by aminolysis of the intermediate chlorofor-mate, or the reaction of an alcohol with an isocyanate, usually prepared from COCl2 [6, 7]. The development of phosgene-free routes to carbamates represents an important synthetic challenge, and several synthetic strategies are currently under investigation in this area. 

Yoshida et al. were the first to report the synthesis of carbamate esters by the direct reaction of aliphatic amines, C02 and alkyl halides [47]. The process involved the O-alkylation of intermediate alkylammonium carbamate salt, and required relatively, severe conditions (333-393 K 4MPa C02), long reaction times (1-2 days) and an excess of amine (2.5 equiv.) with respect to the alkylating agent. The method was shown to be effective only with secondary aliphatic amines which, however, were converted into organic carbamates in low to moderate yield and with modest selectivity because of significant side-formation of N-alkylation products. 

Aresta and Quaranta focused on the direct synthesis of carbamate esters by the reaction of aliphatic primary amines with alkyl halides in the presence of C02. Under the conditions used (293-353 K 0.1 MPa C02 solvent = tetrahydrofuran (THF), MeOH, PhCH3/CH2Cl2 mixtures), the formation of carbamate ester was... 

Scheme 6.5 Direct synthesis of carbamate esters from primary amines, C02, and alkyl halides in the presence of 18-crown-6-ether.

One transformation that is closely related to the synthesis of carbamate esters from alcohols, amines and C02, is the formation of cyclic urethanes, such as oxazolidin-2-ones, by reaction of C02 with 1,2-amino alcohols or their formally dehydrated derivatives, aziridines. 

The synthesis of carbamic esters of 1,2-diols has been achieved by reacting oxiranes and amines in an atmosphere of carbon dioxide under various experimental conditions. ... 

The interest in the synthesis of carbamate esters [12] remains very high owing to their wide utilization [13]. The synthesis of these compounds generally uses phosgene [14] or isocyanates [15] as starting material. These are toxic, harmful compounds and, therefore, it is of interest to discover new synthetic routes to carbamate esters involving the use of less noxious starting materials. 

H. Al-Rawi and A. Williams, Elimination-Addition Mechanisms of Acyl Group Transfer the Hydrolysis and Synthesis of Carbamate Esters, J. Am. Chem. Soc., 1977, 99, 2671. 

Berger, F. M. The anticonvulsant activity of carbamate esters of certain 2,2-disubstituted-l,3-propanediols. J. Pharmacol. Exp. Ther. 1952,104, 229-233. 

An alternative synthetic approach to Boc-protected l -aminoferrocene-l-carboxylic acid 40 was recently described by Rapic and co-workers, and is shown in Scheme 12.7. Hydrolysis of carbamate-ester by an equimolar amount of sodium hydroxide in aqueous ethanol gave 90% of tert-butyl l -carboxy-l-ferrocenecarbamate.52 During the synthesis the symmetrical ferrocenyl-substituted urea, dimethyl l, l -ureylenedi(l-ferrocenecarboxylate) 39 was formed as a by-product (Scheme 12.7).53 The ferrocenium molecules were conjugated through a urea linker, which upon deprotection may be used in condensation reactions. 

Numerous studies support the idea that drug molecules are absorbed through lipid bilayer membranes in the un-ionized state by the process of passive diffusion. The rate of absorption,the pX of the diffusingsolute, and the pH at the absorption site are interrelated. Equation 8.8 demonstrates that the absorption rate of solutes through biological membranes is directly proportional to the value of the oil/water partition coefficient. Houston et al. (16) studied the absorption of a series of carbamate esters through rat everted intes-... 

As mentioned above, organic carbonates can also be used as alkylating agents for the production of carbamic esters. Since such carbonates (e.g., dimethyl carbonate) can be produced on C02 basis (see above), procedures can be envisaged for extensive use of C02 for production of urethanes and polyurethanes. 

Hohhiger, F., The action of carbamic esters and tetraethylpyrophosphate on normal and curarized frog rectus muscle, Br. J. Pharmacol. Chemother., 5, 37, 1950. 

For M=Ru -formamides and amines were the principal products. Substitution ot Fe3(C0)j2 Ru3[Pg.119]

Oxazolidinones are frequently used as chiral auxiliaries in asymmetric transformations, as ligands for metal catalysts, and as precursors to vicinal amino alcohols. These common structural motifs in natural products and pharmaceuticals have spurred interest in the development of methods for their preparation. Espino and Du Bois reported the synthesis of indane-appended oxazolidinone 215 via Rh-catalyzed C-H insertion of carbamate ester 214. A variety of other carbamates was found to be competent substrates for this reaction. The role of magnesium oxide as additive was presumed to be as scavenger of acetic acid generated from the iodinane oxidant. 

Although polyurethane synthesis can be effected by reaction of chloro-formic esters with diamines and of carbamic esters with diols ... 

Post-column hydrolysis of carbamate esters, such as carbaryl, was discussed in Chapter 4, Section 2. Further consideration of anticholinesterase insecticides can be found in Chapter 7, Section 4. 

The Mitsunobu reaction can be used in the preparation of carbamate esters as well (e.g., 234). The reaction proceeds via an in-situ carboxylation of an alkylamine with CO2, followed by an 0-alkylation with an alcohol in the presence of TPP/DEAD. Yields are typically in the 80-90% range. A solid-supported version in which Fmoc-(I)-phenylalanine is tethered to Wang resin via an ester has also been reported. In situ deprotection with a tertiary amine to yield an 0-ammonium carbamate intermediate in the presence of primary aliphatic alcohols and PBuj/ADDP leads to the formation of the corresponding carbamates the carbamates are typically obtained in 40-80% yield with variable purity after TEA cleavage from the resin. 

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