Base-catalysed condensation

The term Knoevenagel Condensation was originally applied to the base-catalysed condensation of the carbonyl ( CO) group of aldehydes and ketones with the reactive methylene group of malonic acid, with loss of w ater ... 

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]. 

SelenazoIidin-2-4-ciiones-2-alkylidene (or arylidene) hydrazones (III) are simply prepared by base-catalysed condensation of a-haloacids on selenosemicarbazones of acetone or benzaldehvdc (Table X-21) (71). 

Baekeland had to make important discoveries before he could bridge the gap between the initial concept and final products. In particular, he found that the base-catalysed condensation of phenol and formaldehyde can be carried out in two parts. If the process is carefully controlled, an intermediate product can be isolated, either as a liquid or a solid, depending on the extent of reaction. At this stage, the material consists of essentially linear molecules and is both fusible and soluble in appropriate solvents. When heated under pressure to 150 °C, this intermediate is converted to the hard, infusible solid known as bakelite . This second stage is the one at which the three-dimensional cross-linked network develops. 

As already shown in Sect. 4.4, ribose-2,4-diphosphate is obtained in a base-catalysed condensation of glycolaldehyde phosphate in the presence of formaldehyde (Muller et al., 1990). The phosphate group in the 4 position of the sugar prevents the formation of a 5-membered furanose ring, but a 6-membered pyranose structure can be formed. 

By base catalysed condensation of the aldehyde 92 with the ketone 73 Sond-heimer and Ojima41 secured a 42% yield of the ketone 93 which underwent cyclisa-... 

A number of substituted chalcones were synthesised by base catalysed condensation of substituted aromatic aldehyde with substituted acetophenone in good yield. These chalcones derivatives were further condensed withortho-phenylene diamine to yield Benzol,5-diazepine derivatives in moderate yield. All the compounds were characterized by 1H-NMR spectral data. These compounds may have good pharmacological activity against bacteria. 

The rate of the base-catalysed condensation of carbonyl compounds with alkyl groups activated by Jt-deficient aromatic systems is enhanced by the addition of quaternary ammonium salts. For example, 2-methylbenzoxazole, 2-methylbenzo-thiazole and 4-nitrotoluene react with a range of substituted benzaldehydes to produce the corresponding 2-styryl derivatives (62-80%) at room temperature over 1 -2 hours [61, 62]. The intermediate alcohol can also be isolated after a short reaction time. 

Isomerisation of the acid-catalysed condensation product (CXXXIV) gave, according to the ultraviolet spectral evidence, equilibrium mixtures of the two isomeric forms. This view was strengthened by the observation that treatment with alkali of the "base-catalysed condensation product (CXXXV) gave a similar equihbrium mixture [3-4 parts of (CXXXV) to one of (CXXXIV)]. 

Ethyl 2-ethylthio-4-chloro-5-pyrimidinecarboxylate (XXIIa), as well as the corresponding4-hydroxy-(XXIIb) and 4-amino-(XXIIIa) derivatives, possess-anti-cytogenic activity on Neurospora crassa [223, 224]. Compounds (XXIIIa, b and c) were found to inhibit the conversion of orotic acid to the uridine nucleotides [202]. Ethyl 2-methylthio-4-(halo-substituted anilino)-5-pyrimidinecarboxylates (XXIV), particularly the o-bromo- and the o-chloro- derivatives, substantially inhibit the growth of five experimental mouse tumours (Krebs-2 ascites carcinoma, Ehrlich carcinoma clone 2, leukaemia L-1210, carcinoma 755 and lymphocytic neoplasm P-288) [225]. Compounds of this type are usually prepared by the base catalysed condensation of ethoxymethylenemalonic esters or related derivatives with urea, thiourea, guanidine, or substituted amidine-type analogues [212, 225-237]. 

Erom natural sources the (R)-enantiomer of ( )-a-ionone is detected with high enantiomeric purity (much more than 99%) hence, the authenticity of ( )-a-ionone is mostly proved via enantio-GC applications [27,65-67]. In the majority of cases synthetic ionones are produced via pseudoionone, prepared by base-catalysed condensation of citral with acetone. After acidic catalysis (using 85% phosphoric acid or concentrated sulphuric acid), this reaction yields racemic ( )-a-ionone and ( )-/l-ionone [68]. 

Contact with the bryozoan Alcyonidium gelatinosum gives rise to Dogger Bank itch , an allergic contact dermatitis. The causative agent is (2-hydroxyethyl)dimethylsulfoxonium ion (1). Synthesis of 1 was achieved by base-catalysed condensation of trimethylsulfoxonium chloride and formaldehyde [26]. 

In the work concerning the mechanism of solid-catalysed aldol reactions, the analogy between the homogeneous and heterogeneous mechanisms is usually assumed [370,372—375]. The mechanism of base-catalysed condensations, which has received much attention (cf. ref. 371), may be pictured in general as... 

Two other related routes to conjugated polymers are the base-catalysed condensation of methyl-substituted aldehydes ... 

The two examples illustrative of the section, however, involve alternative procedures for introducing the required substituent into the a-position of the acet-amidomalonate reagent. In the first (Expt 5.183) the hydroxymethyl group is introduced by a simple base-catalysed condensation with formaldehyde subsequent hydrolysis and decarboxylation yields serine (R = CH2OH). In this case, acidic conditions are preferred for the final hydrolytic stage, and the use of a weakly basic ion exchange resin to obtain the halide-free amino acid from a solution of its hydrochloride is described. 

The forward synthetic reaction is a base-catalysed condensation reaction between two carbonyl compounds, the aldol condensation leading to -hydroxy-aldehydes or / -hydroxyketones followed by dehydration. This sequence is one of the most important carbon-carbon bond forming reactions, and aldol-type condensation reactions are considered in a number of other sections of the text, for example, the Doebner reaction (Section 5.18.3, p. 805), the Knoevenagel reaction (Section 5.11.6, p. 681), the Perkin reaction (Section 6.12.3, p. 1036) and the Robinson annelation reaction (Section 7.2). 

In a modification of a known sequence, base-catalysed condensation of hydrastininium iodide (18) with 6-methoxy-2-nitrotoluene (19) provided (20) and (21). Catalytic hydrogenation of (20), followed by Pschorr cyclization, afforded stephanine (22).44... 

The methylene group adjacent to a ketone may be oxidized by selenium dioxide to give 1,2-dicarbonyl compounds. It is important to carry out base-catalysed condensations of ketones wherever possible under an atmosphere of nitrogen. The reason is that enolate anions are readily autoxidized by the oxygen in air to form hydroperoxides These may then undergo further reaction including decomposition to form diketones. 

Chettaphanin II, isolated from Adenochlaena siamensis, has been assigned the unusual structure (13), which was confirmed by an 2f-ray analysis. The compound can be formed in vitro by the base-catalysed condensation of dihydro-chettaphanin I. The crystal structure of tinophyllone (14), isolated from the roots and bark of Tinomiscium philippinense, has been determined by the direct method, whilst o.r.d. has been used to assign the absolute configuration. Like columbin, which occurs in a related species, it belongs to the cis-A/B-fused clerodane series. 

The third synthesis, by Crombie et al., utilizes the base-catalysed condensation of the trans,trans-phenyl farnesyl sulphone (10) with trans,trans-Qthy farneso-ate to give the ester (11) as a major product via the intermediate (12). Lithium aluminium hydride reduction again yielded presqualene alcohol (1). In each case the labelled synthetic alcohol, as its pyrophosphate, was incorporated by yeast subcellular particles into squalene in ca. 68 % yield. The minor synthetic isomers were not incorporated. 

Acylketene dithioacetal 107 and the corresponding /3-methylthio-a,/3-enone 108 undergo self-condensation and aromatization in the presence of sodium hydride and methyl benzoates in refluxing xylene to give 2,6-bis(methylthio)-4-hydroxyacetophenone (109) and 4-hydroxyacetophenone (110), respectively, in good yields (equation 103) . The possible pathway for the formation of 109 and 110 could involve base-catalysed condensation of either 107 or 108 with methyl benzoates followed by successive inter-and intramolecular Michael additions and elimination of SMe. No reaction is observed in the absence of methyl benzoates. 

Base-catalysed condensation of a-hydroxycarboximidic esters (32) with phosphorus trichloride yields the new heterocycles (33), although minimal evidence has been presented in support of the structure assignment. ... 

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