Condensation basic conditions

The Claisen condensation is initiated by deprotonation of an ester molecule by sodium ethanolate to give a carbanion that is stabilized, mostly by resonance, as an enolate. This carbanion makes a nucleophilic attack at the partially positively charged carbon atom of the e.ster group, leading to the formation of a C-C bond and the elimination ofan ethanolate ion, This Claisen condensation only proceeds in strongly basic conditions with a pH of about 14. 

Furfural reacts with ketones to form strong, crosslinked resins of technical interest in the former Soviet Union the U.S. Air Force has also shown some interest (42,43). The so-called furfurylidene acetone monomer, a mixture of 2-furfurylidene methyl ketone [623-15-4] (1 )> bis-(2-furfurylidene) ketone [886-77-1] (14), mesityl oxide, and other oligomers, is obtained by condensation of furfural and acetone under basic conditions (44,45). Treatment of the "monomer" with an acidic catalyst leads initially to polymer of low molecular weight and ultimately to cross-linked, black, insoluble, heat-resistant resin (46). 

Resorcinol carboxylation with carbon dioxide leads to a mixture of 2,4-dihydroxyben2oic acid [89-86-1] (26) and 2,6-dihydroxyben2oic acid [303-07-1] (27) (116). The condensation of resorcinol with chloroform under basic conditions, in the presence of cyclodextrins, leads exclusively to 2,4-dihydroxyben2aldehyde [95-01-2] (28) (117). Finally, the synthesis of l,3-bis(2-hydroxyethoxy)ben2ene [102-40-9] (29) has been described with ethylene glycol carbonate in basic medium (118), in the presence of phosphines (119). Ethylene oxide, instead of ethyl glycol carbonate, can also be used (120). 

The required triamino-4(3H)-pyrimidinone is prepared in three steps starting from guanidine [50-01-1] (14) (26). Condensation with methylcyanoacetate [105-34-0] (15) under basic conditions, followed by nitrosation of the intermediate [56-06-4] (16), gives... 

These compounds are stable only under basic conditions and must be held at high pH if stored for considerable periods of time. In Step 2, these methylolureas further react under acidic conditions with urea to form the various methylene urea oligomers. Water generated from the condensation reaction is removed by evaporation when producing granular UE products. 

Although most of the reactions of preparative importance involving the a-alkyl carbanions are usually carried out under controlled conditions with NHa /NHs being used as the base, a number of reactions using less severe conditions are known, both in the pyrazine and quinoxaline series. In the case of alkylquinoxalines, where an increased number of resonance possibilities exist, mildly basic conditions are usually employed in condensation reactions. 

Scheme 4b depicts condensation between a hydroxymethyl group and a phenolic ring where the hydroxybenzyl attacks at a ring position that is already hydroxymethylated. In this case, a methylene linkage is produced between the rings with concurrent loss of one mole each of formaldehyde and water. Both Jones and Grenier-Loustalot et al. demonstrated the occurrence of this reaction pathway beyond doubt under basic conditions. 

Under basic conditions, the o-nitrotoluene (5) undergoes condensation with ethyl oxalate (2) to provide the a-ketoester 6. After hydrolysis of the ester functional group, the nitro moiety in 7 is then reduced to an amino function, which reacts with the carbonyl group to provide the cyclized intermediate 13. Aromatization of 13 by loss of water gives the indole-2-carboxylic acid (9). 

The Hinsberg synthesis of thiophene derivatives describes the original condensation of diethyl thiodiglycolate and a-diketones under basic conditions which provides 3,4-disubstituted-thiophene-2,5-dicarboxylic acids upon hydrolysis of the crude ester product with aqueous acid. ... 

Faced with the inapplicability of the standard basic conditions required for the Pfitzinger condensation in the context of their study, Lackey and Stembach developed a modified protocol which allows for the formation of quinolinic acids under acidic conditions. ... 

Carboxylic acids with labile a-methylene protons react with isatin in the presence of strong aqueous base. In the total synthesis of methoxatin, the coenzyme of methanol dehydrogenase and glucose dehydrogenase, Weinreb employs a Pfitzinger condensation of an isatin 37 and pyruvic acid as a key step to provide the 4-quinolinic acid 38 in 50% yield under the standard basic conditions. ... 

Polyacrylamide may be converted into a sulfo-methyl derivative by condensation with formaldehyde and sodium bisulfite under basic conditions. 

Two of the four general carbonyl-group reactions—carbonyl condensations and basic conditions and involve enolate-ion intermediates. Because the experimental conditions for the two reactions... 

Benzodiazepinones condense with aromatic aldehydes under basic conditions to form 3-arylidcne compounds 36.281 306... 

Compound 15 is prepared in two steps acid-catalyzed condensation of the pyrimidinediamine with ethyl aceloacelale provides ester 14, which cyclizes under strongly basic conditions. The pyrimidodiazepinone 15 undergoes ring contraction to 7-isopropenyl-7//-purin-8(9//)-one (16) on prolonged heating under basic conditions.297... 

Resole syntheses entail substitution of formaldehyde (or formaldehyde derivatives) on phenolic ortho and para positions followed by methylol condensation reactions which form dimers and oligomers. Under basic conditions, pheno-late rings are the reactive species for electrophilic aromatic substitution reactions. A simplified mechanism is generally used to depict the formaldehyde substitution on the phenol rings (Fig. 7.21). It should be noted that this mechanism does not account for pH effects, the type of catalyst, or the formation of hemiformals. Mixtures of mono-, di-, and trihydroxymethyl-substituted phenols are produced. 

Condensation reactions between two hydroxymethyl substituents eliminate water to form ether linkages (Fig. 7.23a) or eliminate both water and formaldehyde to form methylene linkages (Fig. 7.23b). Ether formation is favored under neutral or acidic conditions and up to 130°C above which formaldehyde departs and methylene linkages are generated. The methylene linkage formation reaction, which eliminates water and fortualdehyde, is more prevalent under basic conditions. Condensation reactions between hydroxymethyl groups and reactive... 

Resole resins are generally crosslinked under neutral conditions between 130 and 200° C or in the presence of an acid catalyst such as hydrochloric acid, phosphoric acid, p-toluenesulfonic acid, and phenolsulfonic acid under ambient conditions.3 The mechanisms for crosslinking under acidic conditions are similar to acid-catalyzed novolac formation. Quinone methides are the key reaction intermediates. Further condensation reactions in resole resin syntheses under basic conditions at elevated temperatures also lead to crosslinking. 

Condensation reactions of hydroxymethyl groups on phenolic resoles and amines on melamine take place between pH 5 and 6 (Fig. 7.33). Only selfcondensations of hydroxymethyl substituents occur under strongly acidic or basic conditions. 

M-substituted 2-pyridones can be prepared by N-alkylation, under basic conditions (pfCa of the amide proton is 11). The resulting anion can then react on either nitrogen or oxygen depending on the conditions employed [24-27]. Also, several direct methods for the construction of N-substituted 2-pyridones have been reported. Two such examples can be seen in Scheme 3 where the first example (a) is an intramolecular Dieckmann-type condensation [28] and the second (b) is a metal-mediated [2 -I- 2 + 2] reaction between alkynes with isocyanates [29,30]. 

The 3-arylglutaric esters 3 required as substrates were obtained by condensation of 2 equiv. of ethyl acetylacetate with respective benzaldehydes, followed by hydrolysis and decarboxylation of the resulting product under basic conditions. After esterification, ester 3 was obtained in 75% overall yield (R = Cl, = Me) [10]. 

In the course of a synthesis of ( )-nootkatone the keto-ester (148) with ethylidenetriphenylphosphorane gave the cyclohexanone (149), a Dieckmann condensation having occurred under the basic conditions. Among other natural products synthesized using Wittig reagents are... 

A Friedel-Crafts-type reaction of phenols under basic conditions is also possible. Aqueous alkaline phenol-aldehyde condensation is the reaction for generating phenol-formaldehyde resin.34 The condensation of phenol with glyoxylic acid in alkaline solution by using aqueous glyoxylic acid generates 4-hydroxyphenylacetic acid. The use of tetraalkylammonium hydroxide instead of sodium hydroxide increases the para-selectivity of the condensation.35 Base-catalyzed formation of benzo[b]furano[60]- and -[70]fullerenes occurred via the reaction of C60CI6 with phenol in the presence of aqueous KOH and under nitrogen.36... 

The difference between the pH profiles of the two stages of urea-formaldehyde resin synthesis is taken advantage of in the production of these resins (Figure 19.2). In general, the commercial production of urea-formaldehyde adhesive resins is carried out in two major steps. The first step consists of the formation of methylolureas under basic conditions (pH 8 to 9), to allow the methylo-lation reactions to proceed in the absence of reactions involving the condensation of the methylolureas. 

Completion of the total synthesis afforded only six further steps, including the installation of the second 2-aminopyrimidine ring via a second domino sequence. This process presumably involves a conjugate addition of guanidine (2-293) to the enone system of2-292, followed by a cyclizing condensation and subsequent aromatization. Under the basic conditions, the ethyl ester moiety is also cleaved and 2-294 is isolated in form of the free acid, in 89 % yield. Finally, decarboxylation and deprotection of the amino functionality yielded the desired natural product 2-295. 

Volcanic gases contain up to 47% sulphur dioxide (SO2). A group from the University of Hong Kong studied the ability of SO2 to support condensation reactions. Under weakly basic conditions, SO2 dissolved in water forms SO2- ions. Oxidation of these to SO4- proceeds via SO3. The experiments suggest the following reaction mechanism ... 

Diaza compound 669 condensed with bromobutyryl chloride under classical basic conditions gives bicyclic derivative 670. This compound can be further functionalized, for example, via classical enolate chemistry (Scheme 110)... 

Similarly, condensation of 206 with carbon disulfide under basic conditions gives rise to the mercapto-substituted tricyclic system 207 in good yield (Equation 55) <2000AF904>. This approach has also been used for related systems of substituted pyrimidines <1999JHC1119, 2000PS( 163) 1 >. Hydrazine-substituted pyrimidines have also been reacted in an analogous manner <1998JRM1248>. 

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