Aldehydes base-catalysed

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 ... 

Which giyes formaldehyde as one of the starting materials. Base-catalysed reactions with this yery reacfiye aldehyde often giye poor yields because of polymerisation and other side reactions. The Marmich reaction is used instead ... 

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]. 

According to Muller (1990) this aldehyde can give ribose-2,4-diphosphate in the presence of formaldehyde via a two-step, base-catalysed reaction. This reaction provides a route to ribose derivatives, and thus to the nucleic acids. 

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-... 

The cyclizations to obtain cyclic thioureas have been performed using thiocarbonyldiimidazole.232 Reaction of methyl acetoacetate, thiourea and an aliphatic aldehyde in the presence of the zinc iodide (Znl2) was studied. Under the normal pressure, reaction has not been occurred whereas at high pressure (300 MPa) conditions 3,4-dihydropyrimidine-2-thione was obtained only in 10% yield.233 The same one-pot three-component cyclocondensation reaction in the presence of iodide (I2) provides a variety of 3,4-dihydropyrimi-dine-2-thione in high yields.234 Condensation reaction of thioureas with a,p-unsaturated ketones in the presence of the sodium methoxide in methanol affords 3,4-dihydropyrimidine-2-thione derivatives.235,236 Acylation of N,N -disubstituted thioureas with methyl malonyl chloride followed by base-catalysed cyclization leads in the formation of l,3-disubstituted-2-thiobarbituric acids (Scheme 78).237... 

A simple two-step protocol for the generation of a terminal diene is to add allyl magnesium bromide to an aldehyde or a ketone and subsequent acid or base catalysed dehydration (equation 34)72. Cheng and coworkers used this sequence for the synthesis of some indole natural products (equation 35)72a. Regiospecific dienones can be prepared by 1,2-addition of vinyllithium to a,/l-unsaturated carbonyl compounds and oxidative rearrangement of the resulting dienols with pyridinium dichromate (equation 36)73. 

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 base-catalysed Michael addition of a,/J-unsaturated nitro compounds 363 to electron-deficient olefins 364 (R4 = Ac, CC>2Me or CN) results in the formation of ally lie nitro compounds 365 aldehydes give alcohols 366 in this reaction409. 

Methylenesulphones are more acidic than the simple esters, ketones and cyano compounds and are more reactive with haloalkanes [e.g. 48-57] to yield precursors for the synthesis of aldehydes [53], ketones [53], esters [54] and 1,4-diketones [55] (Scheme 6.4). The early extractive alkylation methods have been superseded by solidtliquid phase-transfer catalytic methods [e.g. 58] and, combined with microwave irradiation, the reaction times are reduced dramatically [59]. The reactions appear to be somewhat sensitive to steric hindrance, as the methylenesulphones tend to be unreactive towards secondary haloalkanes and it has been reported that iodomethylsulphones cannot be dialkylated [49], although mono- and di-chloromethylsulphones are alkylated with no difficulty [48, 60] and methylenesulphones react with dihaloalkanes to yield cycloalkyl sulphones (Table 6.5 and 6.6). When the ratio of dihaloalkane to methylene sulphone is greater than 0.5 1, open chain systems are produced [48, 49]. Vinyl sulphones are obtained from the base-catalysed elimination of the halogen acid from the products of the alkylation of halomethylenesulphones [48]. 

In temperature-sensitive reactions, aryl aldehydes and ketones produce the trimethylcarbinols at ca. 0°C and the glycolic acids at ca. 56°C in competition with the base-catalysed Cannizzaro or condensation reactions [3, 5, 8]. 2- and 3-Formylpyridines produce the trichloromethylcarbinols (20-30%), whereas 4-formylpyridine undergoes the Cannizzaro reaction [9]. Formylferrocene is converted into the a-ferrocenylglycolic acid (35%) [10],... 

A degree of stereoselective control of the course of a reaction, which is absent or different from that prevalent when the reaction is conducted in the absence of quaternary ammonium salts, may be achieved under standard phase-transfer catalysed reaction conditions. The reactions, which are influenced most by the phase-transfer catalyst, are those involving anionic intermediates whose preferred conformations or configurations can be controlled by the cationic species across the interface of the two-phase system. For example, in the base-catalysed Darzens condensation of aromatic aldehydes with a-chloroacetonitriles to produce oxiranes (Section 6.3), the intermediate anion may adopt either of the two conformations, (la) or (lb) which are stabilized by interaction across the interface by the cations (Scheme 12.1) [1-4]. 

Concerted acid-base catalysed enolizations of a range of simple aldehydes and ketones have been measured in water at 25 °C, using a range of substituted acetic acid-acetate buffers.The buffer plots yield rate constants for acid (A a) and base ( b) catalytic terms in the normal way at low buffer concentrations. Extension up to higher concentrations (as far as [total buffer] = 2 m, typically) yields the third-order term ( ab) via upward curvature of the plots. While ab does not have a simple correlation with either k or b, it does correlate with their product, i.e. 

The reaction is best carried out in the appropriate anhydrous aldehyde or ketone, which thus functions as reactant and solvent, or in ethanol, in the presence of an optimum of 1.5 equivalents of strong acid per equivalent of arylbiguanide (base). Acetic acid as a catalyst produces, anomalously, the "base-catalysed anilino-triazines (126, 443). The reaction time varies from one hour to two weeks. The rates diminish in the following order ... 

Aldehydes and ketones nndergo acid- and base-catalysed halogenation in the a position. This is also dependent on enolization or the formation of enolate anions. 

The reaction is usually carried out in acid solution, but may also be base catalysed. This is the condensation between aldehydes, ammonia or a primary or secondary amine and a compound containing at least one active hydrogen atom e.g., ketones, b-ketoesters, b-cyanoesters, nitroalkanes, alkynes with C°H). For example. 

KOH-ethylene glycol. This latter reaction apparently involves an unusual base-catalysed Beckmann fragmentation and reduction of the resultant aldehyde by KOH-ethylene glycol. 

Aldol condensation reaction may be either acid or base catalysed. However, base catalysis is more common. The product of this reaction is called an aldol, i.e. aid from aldehyde and ol from alcohol. The product is either a P-hydroxyaldehyde or P-hydroxyketone, depending on the starting material. For example, two acetaldehyde (ethanal) molecules condense together in the presence of an aqueous base (NaOH), to produce 3-hydroxybutanal (a P-hydroxyaldehyde). 

The Cannizzaro reaction, that is, the base-catalysed disproportionation of a carbonyl compound to an alcohol and a carboxylic acid, has gained some importance as an economically viable alternative to the reduction with borohydrides. However, the reaction is restricted to carbonyl compounds without any a-hydrogen, which do not undergo competing aldol reactions. Thus, mainly aromatic aldehydes are used for this kind of transformation. The protocols developed for microwave applications typically involve solvent-free conditions using alumina as the solid support. Under these conditions, a significant acceleration of the reaction was achieved. 

The same authors have also reported the synthesis of 2-amino quinolines46, Scheme 5.28. Secondary amines were reacted with aldehydes to form enamines subsequent addition of 2-azidobenzophenones initially forms triazoline intermediates, which undergo a thermal rearrangement and intermolecular base-catalysed cyclocondensation to produce 2-amino quinolines. The reactions were run at 180°C for 10 min (the time includes 3 min required for enamine formation) to give the products in 57-100% yields. 

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

The second example is an interesting synthesis of the heterocyclic amino acid tryptophan (R = 3-indolymethyl) which involves the initial base catalysed 1,4-addition (the Michael reaction, Section 5.11.6, p. 681) of diethyl acetamido-malonate to the oc,/ -unsaturated aldehyde, acrylaldehyde, yielding the aldehydic derivative (38). The derived phenylhydrazone (39) is then cyclised under acidic conditions (see Expt 8.26) to form the indolylacetamidomalonate derivative (40) which is then converted into the corresponding a-amino acid (i.e. tryptophan) in the usual way (Expt 5.184). 

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). 

A range of Lewis bases catalyse the addition of TMSCN to aldehydes, with phosphines and amines the most efficient.247 Kinetic studies indicate that the orders of aldehyde, Lewis base (LB), and TMSCN are 1, 1, and 0, suggesting an Me3Si-LB+ CN ion pair as an intermediate. However, chiral phosphines and amines gave very... 

The Fewis base-catalysed additions of alkynyl nucleophiles to aldehydes, ketones, and imines have been described.161 Mechanistic studies strongly indicated that the use of new triethoxysilylalkynes facilitate access of a reactive hypervalent silicate intermediate (Scheme 24). 

The base catalysed reaction of 3-azidochroman-4-one with simple aldehydes affords the aldol product, but reaction of the enolate with acetone is slower than loss of N2 from the azido function and... 

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