Carboxylic esters from

The main example of a category I indole synthesis is the Hemetsberger procedure for preparation of indole-2-carboxylate esters from ot-azidocinna-mates[l]. The procedure involves condensation of an aromatic aldehyde with an azidoacetate ester, followed by thermolysis of the resulting a-azidocinna-mate. The conditions used for the base-catalysed condensation are critical since the azidoacetate enolate can decompose by elimination of nitrogen. Conditions developed by Moody usually give good yields[2]. This involves slow addition of the aldehyde and 3-5 equiv. of the azide to a cold solution of sodium ethoxide. While the thermolysis might be viewed as a nitrene insertion reaction, it has been demonstrated that azirine intermediates can be isolated at intermediate temperatures[3]. 

Preparation of carboxylic esters from carboxylic acids and alcohols H+ R-C-OH + R OH R-C-OR +H20 II II 0 0... 

A solution of trifluoroacetic acid in toluene was found to be advantageous for cyclization of pyruvate hydrazoncs having nitro substituents[4], p-Toluene-sulfonic acid or Amberlyst-15 in toluene has also been found to give excellent results in preparation of indole-2-carboxylate esters from pyruvate hydra-zones[5,6J. Acidic zeolite catalysts have been used with xylene as a solvent to convert phenylhydrazines and ketones to indoles both in one-flask procedures and in a flow-through reactor[7]. 

The apparent abnormal formation of ethyl pyrrole-2-carboxylate from the reaction of ethyl chloroformate and alkali metal salts of pyrrole could be accounted for by a thermal rearrangement during the isolation of the products. However, whilst this may be partly correct, an analysis of the reaction products prior to their isolation has established (77CJC4103) the formation of the thermodynamically more stable 2-carboxylic ester from the 1-isomer by a reaction sequence shown in Scheme 36. 

The formation of butane tetra-carboxylic ester from ethylene dibromide and mono-sodium-malonic ester ... 

A case of internal condensation similar to that of succinic ester, is the formation of keto-pentamethy-lene carboxylic ester from 1 4-butane dicarboxylic ester ... 

A procedure for obtaining indole-3-carboxylate ester from the f-pyrrolidino-o-nitrostyrene intermediates in the Leimgruber-Batcho indole synthesis was demonstrated. Although ethyl chloroformate is evidently not reactive enough, phosgene followed by methanolysis effects f) -carbomethoxylation. Reductive cyclization then gives the indole esters. <95SC95>... 

The mechanism for the attachment of a new nucleotide to a growing DNA chain shown in Figure 27.4 is very similar to the mechanism for the formation of a carboxylic ester from an alcohol and a carboxylic anhydride. Suggest the steps in the mechanism for this reaction ... 

Radical nucleophile oxidation based on one-electron oxidation, known as the Minisci reaction, is employed for the functionalization of /V-heterocycles with acidic hydrogen peroxide in the presence of iron(II) salts (Figure 3.112).472 A range of A-heterocycles (pyridines, pyrazines, quinolines, etc.) which are activated towards attack by nucleophilic radicals when protonated are suited to this chemistry. The Minisci reaction is suitable for the preparation of carboxylic amides (from formamide), carboxylic esters (from pyruvic esters via a hydroxyhydroperoxide), aldehydes (from 1,3,5-trioxane) and alkylated pyridines (either from carboxylic acids or from alkyl iodides in dimethyl sulfoxide).473 The latter reaction uses dimethyl sulfoxide as the source of methyl radical (Figure 3.112). 

The hydroesterification of alkenes is a versatile method for obtaining carboxylic esters from alkene, CO, and alcohol (Eq. 11.13) [45, 46]. 

Davis, F. A., Liu, H., Zhou, P., Fang, T., Reddy, G. V., Zhang, Y. Aza-Darzens asymmetric synthesis of N-(p-toluenesulfinyl)aziridine 2-carboxylate esters from sulfinimines (N-sulfinyl imines). J. Org. Chem. 1999, 64, 7559-7567. 

V. Karl, A. Dietrich, A. Mosandl (1994) Gas chromatography - isotope ratio mass spectrometry measurements of some carboxylic esters from different apple varieties. Phytochem. Anal. 5, 32-37... 

The selective formation of carboxylic esters from aldehydes and alcohols in the presence of a hydrogen acceptor such as diphenylacetylene is catalyzed by Ru3(CO)12. For instance, benzyl benzoate is obtained from ben-zaldehyde and benzyl alcohol in 72% yield (CT 54) after 2 hr, when the reaction is carried out without solvent at 147°C (403) ... 

Saitoh. K.. Shiina. I., and Mukaiyama, T., O,O -Di(2-pyridyl) thiocarbonate as an efficient reagent for the prepaiation of carboxylic esters from highly hindered alcohols, Chem. Lett., 679, 1998. Williams, D.R., Werner. K.M.. and Feng, B., Total synthesis of rhizoxin D, Tetrahedron Lett., 38, 6825, 1997. 

X" = NOj- From Amberlyst A-26 or Amberlite IRA 400 From Amberlite IRA 900 (C1-) by treatment with NaNO, soln. 3 Synthesis of nitroalkanes and alkyl nitrites from alkyl halides. - a-Nitro carboxylic esters from a-bromo esters alkyl-nitro compounds from primary, secondary and benzylic bromides (formation of nitrites was not detected). ... 

An improved two-step synthesis of cyclopropane-carboxylic ester from y-butyro-lactone makes use of a base-induced elimination ... 

Figure 15 Schematic representation of the procedure used for patterning biotin ligands onto SAMs consisting of activated carboxylic esters. (From J. Lahiri, E. Ostuni, and G.M. Whitesides. Langmuir 15 2055-2060, 1999. With permission.)...

The formation of a,P-epoxy carboxylic esters from carbonyl compounds and a-halo esters is not just an undesired side reaction, but is also an important synthetic method known as Darzens reaction. 

Cerium(IV) salts are very useful reagents for the functionalization of alkenes. In this section, only a few representative examples are shown. More examples can be found in reviews written by Nair and coworkers (Nair et al., 2002, 2004). The halogenation of alkenes with CAN has been described in section 6.7. Alkenes react with carboxylic acids in presence of cerium(IV) sulfate to yield carboxylic esters (scheme 50) (Horiuchi et al., 2003). The addition reaction follows Markovnikov s rule. The carboxylic acid also acts as solvent. This reaction provides a simple method for the preparation of carboxylic esters from alkenes. 

Although the preparation of benzyl carboxylate esters from benzyl bromide and carboxylate anions is not the most common route to these compounds, the reaction is possible when carried out in DMF or using zinc carboxylates. ... 

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