Esters and Amides of Carbonic Acid

Esters and Amides of Carbonic Acid 1032 EssentialTerms 1035 Study Problems 1037... 

Apart from aryl esters and amides of carboxylic acids, aryl carbonates, and carbamates, other types of organic compound have been reported to undergo PFR. They include oxalates, formiates, sulfonates, sulfonamides, thioesters, selenoesters, and telluroesters. 

Geranyl chloride can be prepared from geraniol by the careful use of triphenylphosphine in carbon tetrachloride. Tris(dimethylamino)phosphine reacts with carbon tetrachloride to form the complex (42) which can be used to form the enol esters (43) from acid anhydrides. Similarly, aldehydes form the alkenes (44), and esters or amides of trichloroacetic acid are converted to glycidic esters. ... 

Isocyanates react with alcohol nucleophiles to give urethanes—hybrids between carbonates and ureas—half-esters and half-amides of carbonic acid. Nucleophilic attack occurs at the very reactive linear (sp) carbon in the centre of the isocyanate. 

Ureidobenzoic acids and derivatives 1 which are readily available from anthranilic acid derivatives and potassium cyanate (cf. p 27) can be cyclized to quinazoline-2,4(l/f,3//)-diones 2 in generally excellent yields. This method makes possible the synthesis of some quinazoline-2,4(1//,3//)-diones on a kilogram scale. The cyclization is usually performed in alkaline medium although cyclizations in acidic mediumhave also been reported. A detailed mechanistic and kinetic study of intramolecular nucleophilic displacement by the ureido func-tional group at the carbonyl carbon of esters and amides of 2-urcidobenzoic acidsand 2-ureidobenzoic acid itself " is available. 

Despite the presence of a formally divalent carbon atom, CO is not in fact a particularly reactive molecule and much of its chemistry depends on the use of either extreme conditions, energetic reagents or some form of catalysis. Perhaps the simplest examples of such catalysis are found in the reactions of carbon monoxide with protic reagents such as alcohols or secondary amines, affording esters or amides of formic acid. These reactions are catalyzed by alkoxide or amide anions, respectively, and, as shown in Scheme 1, the key step is nucleophilic attack on CO by the catalyst to give a strongly basic alkoxyacyl or aminoacyl anion which is immediately trapped by proton transfer from the alcohol or amine, so generating the catalytic species. 

Further reports of the reaction of tris(dimethylamino)phosphine and carbon tetrachloride with aldehydes and esters or amides of trichloroacetic acid have appeared. Addition of tertiary phosphines to the imide (35) gave (36) after hydrolysis. ... 

N-Substituted esters of carbamic acid (carbamic acid is the mono-amide of carbonic acid) are compounds containing the -NHCOOR group, and are named carbamates or urethanes. Urethane (or urethan) is also used as a name for ethyl carbamate 515, NH2COOEt (a compound which has been shown to act as a carcinogen in some animals), and sometimes even for the whole class of carbamate esters. It is formed by reaction of ethanol with isocyanic acid 516 or urea 517. Since "urethane nomenclature may be confusing there is litde justification in its continued use. 

Trichloroacetic acid K = 0.2159) is as strong an acid as hydrochloric acid. Esters and amides are readily formed. Trichloroacetic acid undergoes decarboxylation when heated with caustic or amines to yield chloroform. The decomposition of trichloroacetic acid in acetone with a variety of aUphatic and aromatic amines has been studied (37). As with dichloroacetic acid, trichloroacetic acid can be converted to chloroacetic acid by the action of hydrogen and palladium on carbon (17). 

Various nucleophiles other than methanol can be introduced onto the carbonyl carbon. Anodic oxidation of acylsilanes in the presence of allyl alcohol, 2-methyl-2-propanol, water, and methyl /V-methylcarbamate in dichlorometh-ane affords the corresponding esters, carboxylic acid, and amide derivatives (Scheme 24) [16]. Therefore, anodic oxidation provides a useful method for the synthesis of esters and amides under neutral conditions. 

Phenyllactic acid is converted to the (S)-( - )-hydroxyketone via its ester and amide. Reduction of the (- )-epoxychalcone yields the ( + )-rotating a-hydroxyketone. Therefore the configuration of the a-carbon of the epoxy-chalcone must be R. Since epoxychalcones are derived from /rans-chalcones, the configuration of the (3-carbon in the epoxychalcone must be 5, as shown in Figure 12. 

A number of other methods exist for the a halogenation of carboxylic acids or their derivatives.134 The acids or their chlorides or anhydrides can be a chlorinated by treatment with CuCl in polar inert solvents (e.g., sulfolane).135 Acyl halides can be a brominated or chlorinated by use of N-bromo- or N-chlorosuccinimide and HBr or HC1.136 The latter is an ionic, not a free-radical halogenation (see 4-2). Direct iodination of carboxylic acids has been achieved with L-Cu(II) acetate in HO Ac.137 Acyl chlorides can be a iodinated with L and a trace of HI.138 Carboxylic esters can be a halogenated by conversion to their enolate ions with lithium N-isopropylcyclohexylamide in THF and treatment of this solution at - 78° with I2138 or with a carbon tetrahalide.139 Carboxylic acids, esters, and amides have been a fluorinated at -78°C with F2 diluted in Ni.,4°... 

The search for RNAs with new catalytic functions has been aided by the development of a method that rapidly searches pools of random polymers of RNA and extracts those with particular activities SELEX is nothing less than accelerated evolution in a test tube (Box 26-3). It has been used to generate RNA molecules that bind to amino acids, organic dyes, nucleotides, cyano-cobalamin, and other molecules. Researchers have isolated ribozymes that catalyze ester and amide bond formation, Sn2 reactions, metallation of (addition of metal ions to) porphyrins, and carbon-carbon bond formation. The evolution of enzymatic cofactors with nucleotide handles that facilitate their binding to ribozymes might have further expanded the repertoire of chemical processes available to primitive metabolic systems. 

Uncatalyzed hydrolysis of a peptide linkage is very slow with f1/2 at neutral pH and 25°C of 300-600 years.189 Both acids and bases catalyze hydrolysis, but enzymes are needed for rapid digestion. The carbonyl group C=0 is highly polarized, with the resonance form C+-0 contributing substantially to its structure. An attack by a base will take place readily on the electrophilic carbon atom. While the reactivity of the carbonyl group in esters and amides is relatively low... 

Apart from C02 and metal carbonates, the most abundant carbonyl compounds of natural origin are carboxylic esters and amides. These occur as fats and lipids, which are esters of long-chain alkanoic acids (pp. 789-791), and as proteins, which are polyamides of natural amino acids. The same struc-... 

Carbonyl electrophiles are obviously a very important group of electrophiles that react successfully with a spectrum of carbon nucleophiles. Among carbonyl electrophiles, however, large differences in reactivity are observed. Acid chlorides are very reactive electrophiles whereas esters and amides are much weaker and fail to react with several classes of carbon nucleophiles. Aldehydes and ketones are probably the most widely utilized groups of carbonyl electrophiles and exhibit moderate electrophilic reactivity. No matter what carbonyl electrophile is used, however, it reacts by nucleophilic addition to the carbonyl carbon to produce a tetrahedral intermediate. The ultimate reaction product reflects subsequent chemistry of the tetrahedral intermediate. 

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