Knoevenagel carbanions, with

Such important processes as alkylation of arylacetonitriles, cyclopentadiene hydrocarbons, aldehydes and ketones, esters, sulfo-nes etc., condensation of carbanions with aldehydes and ketones, the Knoevenagel, Darzens, Michael and related reactions as well as many reactions involving sulfonium and phosphonium ylides have been successfully carried out under these conditions. 

Ethyl cyanoacetate in the presence of piperidine may also be used as the carbanionic component in reactions with salicylaldehyde. The initial Knoevenagel condensation is followed by a [l,7]-sigmatropic shift and cyclization to the 2-iminochromene derivative which adds another cyanoacetate molecule (67AP1). 

Furthermore, the carbanion also may be added to a carbonyl group of another molecule, with formation of a new CC bond. Synthetic applications are the aldol condensation and the diacetonealcohol condensation. The acid strength of CH bonds in alpha position to COO-, COOR, or CN groups is extremely low (p > 20) and condensation reactions of the corresponding anions must be carried out in the absence of water (Claisen, Perkin, and Knoevenagel condensations). 

Certain substituted sulfones may be obtained by special methods for instance, vinyl sulfones (82) may be formed by addition of a sulfonyl carbanion (83) to a carbonyl compound followed by elimination (Scheme 34). An example when X = H is the synthesis of methyl styryl sulfones (84) by the Knoevenagel condensation of an aromatic aldehyde with a methanesulfonylacetate (85) followed by dealkylation-decarboxylation of the intermediate product by treatment with lithium iodide in DMF (Scheme 35). 

The Knoevenagel reaction (Scheme 6.20) involves the reaction of aromatic aldehydes with a variety of molecules CH2XY. The groups X and Y may be the same or different, but are invariably electron withdrawing, so creating an activated methylene group from which the carbanion CHXY is produced. The reaction is usually carried out in pyridine solution, with piperidine as the basic catalyst. The reactions of benzaldehyde with propane-1,3-dinitrile [malononitrile, CH2(CN)2] and diethyl propane-1,3-dioate [diethyl malonate, CH.,(CO,Et)2] are illustrative. In both cases, manipulation of the CH=CX2 group in the product allows the synthesis of other compounds. 

The role of calcite and fluorite used in ball-milling process was proposed. When the minerals are mechanically crushed, the newborn solid surface is activated with the naked ionic species in situ generated. The naked carbonate and fluoride anions act as a strong base capable of deprotonating the active methylene compounds, with the consequent formation of a carbanion stabilized via the coordination with calcium cation, which combines with a carbonyl compound, eventually leading to the Knoevenagel product. 

A basic site can be described in terms of its ability to accept a proton (Bronsted base) or to donate electrons (Lewis base). In order for base-catalysed reactions to occur, the basicity must be sufficient to stabilise an anionic or polarised species with a significant negative charge that forms part of the catalytic cycle. For a typical base-catalysed C-C bond formation reaction (such as a Michael addition or the Knoevenagel condensation (Scheme 9.18)), the basic site stabilises the intermediate carbanion, which can then act as a nucleophile in the C-C bond formation. Surface sites on MgO are typical strong basic sites. 

Retrosynthetic disconnection of hexahydrocannabinol 1 following the path of an intramolecular hetero DiELS-Alder reaction leads to the o-quinonemethide 2 as an electron-deficient hetero-1,3-diene 2 arises from a Knoevenagel alkenylation of citronellal 3 with the carbanion resulting from deprotonation of the CH-acidic methylene group of the keto tautomer 4 of 5-pentylresorcinol known as olivetol. 

In contrast to alkylation in liquid ammonia/sodamide, only the mono-alkylated product is formed. A variety of carbanion reactions can be carried out. Ketones undergo the Knoevenagel reaction. The Wittig reaction is successful with aldehydes, and olefines can be transformed into halocyclopropanes via carbene addition (e.g. equation 12.14). 

Synthesis of Esters and Aldehydes. Monoalkylation of methylthiomethyl p-tolyl sulfone (MT-sulfone) with an alkyl halide is achieved by the action of a phase-transfer catalyst (PTC) in toluene-50% aq NaOH. sodium hydride and butyl-lithium also generate a carbanion of MT-sulfone. Arylmethyl derivatives of MT-sulfone are prepared by sodium borohydride reduction of the Knoevenagel condensation products with aromatic aldehydes. The monoalkylated products are converted into the corresponding methyl esters (eq 1). This functionalization can be utilized for synthesizing a-alkoxy carboxylic esters (eq 2) and Q -amino acids (eq 3). ... 

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