Esters illustrative example

Carboxylic acids can also be attached to solid supports as amides, imides, and thiol esters. Illustrative examples of the saponification of such linkers are listed in Table 3.5. Thiol esters are more sensitive towards nucleophilic attack than the corresponding esters, and can be readily saponified. Resin-bound thiol esters have, however, mainly been used for the preparation of amides by nucleophilic cleavage with amines (see Section 3.3.3). 

As an illustrative example, the IR spectrum of tetrakis(2-hydroxy-propyl)adi-pamide (Fig. 4) was measured as a function of temperature. It appeared that ester absorptions (C=0,1720 -1740 cm ) appeared rapidly after melting and increased to a certain constant value with respect to the amide absorptions (C=0,... 

A full discussion of these models will follow in Section 21.3. At this point we will deal only with a special version of Eq. 21-30 in which there is no back-reaction from B to A and no external input of chemical B. As an example imagine the case of the pollution of a pond by a pesticide A that in the water is transformed into another compound B that is more toxic than the original compound. For instance, thiophos-phoric acid ester is transformed to the corresponding phosphoric acid ester (see Chapters 2 and 13). Then it would be important to predict the maximum concentrations of A and B in the pond and to estimate the necessary time until the pollutant concentration has fallen below a certain threshold. Such a case will be discussed in Illustrative Example 21.4 below. 

Their potential in azapeptide synthesis is similar to that of the N-activated esters or isocyanates as they react readily with hydrazides 15 to give the azapeptides 16 with release of imidazole or 1,2,4-triazole as shown in the general Scheme 5 and in an illustrative example (Scheme 6)J32 ... 

As an illustrative example, the monomers used for the preparation of a typical polyacrylamide support (Pepsyn) and its schematic representation are sketched in Figure 2.6. The ester functionality, obtained by copolymerization with A-acryloylsarco-sine methyl ester, can be used as the attachment point for a suitable linker. This can be achieved by aminolysis with ethylenediamine, followed by acylation of the resulting primary amine with 3-(4-hydroxymethyl)phenylpropionic acid [163] or other linkers. Similar supports have been prepared by copolymerization of protected allylamine [37] or lV-(acryloyl)-l,3-diaminopropane [173] with V,lV-dimethylacrylamide and... 

Most C,H-acidic compounds can be condensed with aldehydes or ketones to yield alkenes. Some of these reactions have also been realized on insoluble supports, with either the C,H-acidic (nucleophilic) reactant or the electrophilic reactant linked to the support. Some illustrative examples are listed in Table 5.6. Polystyrene-bound malonic esters or amides, cyanoacetamides, nitroacetic ester [95], and 3-oxo esters undergo Knoevenagel condensation with aromatic or aliphatic aldehydes. Catalytic amounts of piperidine and heating are generally required, although reactive substrates can react at room temperature. 

A general convenient alkyl methyl ketone synthesis, which utilises the /7-keto ester system as an intermediate, involves the acylation of a malonate ester by way of the ethoxymagnesium derivative. Hydrolysis and decarboxylation to the ketone is accomplished by heating in acid solution the synthesis of cyclohexyl methyl ketone is the illustrative example (Expt 5.96). 

One preparative procedure for achieving this reaction involves the acylation of the magnesium enolate of diethyl malonate with an acid chloride in benzene solution (cf. Expt 5.96), and the resulting aclymalonic ester is then heated to 200 °C with an arylsulphonic acid to effect the decarbethoxylation step. An illustrative example is the preparation of ethyl 3-oxopentanoate (ethyl propionyl-acetate, Expt 5.177). 

An illustrative example of oxirane formation by the action of alkali on a / -halohydrin is to be found in the reaction sequence involved in the Darzens glycidic ester synthesis (Section 5.7.6, p. 598). Three target molecules, namely 2-phenylaziridine (4), methyl (S)-thiiranecarboxylate (5) and cyclooctene sulphide (6), are selected here to exemplify this intramolecular cyclisation reaction type. 

In analogy with iron-catalyzed Barbier-type reactions with Sml2 (cf. Scheme 8.5), intramolecular nucleophilic acyl substitutions (SNt) can be used to prepare cyclic ketones from esters [50]. An illustrative example is shown in Scheme 8.13 [51], Again, tris(l,3-diphenyl-l,3-propanedionato)iron(III) [Fe(dbm)3] is used as the catalyst. Compound 40 is obtained as one racemic diastereoisomer. 

The oxidative introduction of carboxylic functions to nanotubes provides a large number of CNT-functional exploitations and permits covalent functionalization by the formation of amide and ester linkages and other carboxyl derivatives [24]. Bifunctional molecules (diamines, diols, etc.) are often utilized as linkers. More illustrative examples are nanotubes decorated with amino-functionalized dendrimers, nucleic acids, enzymes, etc., and the formation of bioconjugates of CNTs [96]. 

An illustrative example of a change in chemoselectivity is the inversion of substrate specificity of the serine protease Subtilisin Carlsberg in the transesterification reaction of ethyl esters of A-acetyl-L-serine and A-acetyl-L-phenylalanine with 1-propanol, measured in twenty anhydrous organic solvents. The enzyme-catalysed reaction with the serine substrate is strongly favoured in dichloromethane, while the reaction with the phenylalanine substrate is preferred in t-butylamine, with a 68-fold change in substrate specificity [313]. 

The thiol sulfur atom is a powerful nucleophile and can participate in nucleophilic substitution at a saturated carbon atom when this is attached to a good leaving group L (Scheme 5). An illustrative example is provided by the condensation of a thiol with an acyl halide to yield the corresponding thiolocarboxylic acid ester (Scheme 5). 

A wide variety of sulfamate esters have been synthesised and screened as herbicides, pharmaceutical agents and sweeteners (see Chapter 11, p. 240). Sulfamates containing a primary amino group (124) are conveniently prepared by condensation of the appropriate alcohol with sulfamoyl chloride (125) in DMF in the presence of sodium hydride (Scheme 50). An illustrative example is provided by the conversion of substituted p-phenylethanols (126) to the corresponding sulfamates (127) (Scheme 50). Compounds of type (127) exhibit anticonvulsant and carbonic anhydrase activity and may be useful in the treatment of epilepsy and glaucoma. Sulfamoyl chlorides (125) may be prepared by treatment of amines or amine hydrochlorides with sulfuryl chloride (128). An analogous reaction also occurs with dialkyl sulfonamides (129) (Scheme 51). 

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