Reactions Initiated by the Attack of Anions

Michael Condensation. One of the best-known examples of addition to a carbon-carbon double bond initiated by the attack of an anion is the Michael condensation in which compounds containing active methylene groups can be added to a,/3-unsaturated molecules. An example is the addition of malonic ester to benzalacetophenone 23 

A very large number of active methylene components and acceptor components have been used successfully.24 

It is interesting that from Michael condensations three different kinds of products have been obtained.23 (1) A normal product such as shown 

The three possible products may be illustrated by the condensation of benzalacetophenone and ethyl methylmalonate.26 

28 In the reaction between benzalacetophenone and ethyl methylmalonate, this particular product has not been isolated. It is, however, illustrative of the structure which would be expected of a rearrangement product. See footnote 25a. 

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In the following sections a number of addition reactions initiated by the attack of anions and cations will be discussed. 

Chameides and Davis (1982) first proposed that the reaction of aqueous hydroxyl radicals with HS03 and SO3 may represent a significant pathway for the conversion of S(IV) to sulfate in cloudwater. The reaction chain is initiated by the attack of OH on HS03 and SO3- to form the persulfite radical anion, SOJ (Huie and Neta 1987) ... 

The reaction mechanism of the DNA (cytosine-5)-methyltransferase-catalyzed cytosine methylation was investigated at the MP2 and DFT levels [98JA12895]. This system has been modeled by 1-methylcytosine 117, methylthiolate, and trimethylsulfonium. The cytosine methylation is initiated by an attack of the anionic methylthiolate at Cg of the cytosine ring (Scheme 77). The formation of the methylthiolate adduct 118 of the neutral 117 was found to be endothermic in the gas phase and in solution. However, the MP2 and DFT results differ... 

At ordinary temperature and pressure quartz is the stable modification of silica. Quartz does not noticeably react with water but is readily attacked by HF. A less dense metastable modification of Si02 called silica W [after Weiss and Weiss (35)] reacts readily with water and forms a yellow silver silicate in contact with an aqueous solution of AgNOs. Another newly discovered but dense modification of Si02, called silica C [after Coes (6)], which is also metastable under ordinary conditions, is so unreactive that even the smallest crystals are not noticeably attacked by HF. The rates of the reactions of Si02 are determined by the polarizability of the O-2 ions. The O-2 ions are most polarizable in the low density form (silica W) and least polarizable in the high density form (silica C). The reactions of silica with water are initiated by the penetration of protons into the electron clouds of the O-2 ions and the rate of proton penetration increases with increasing polarizability of the anions. The phenomena described are strictly rate phenomena, because neither quartz nor the two metastable forms of silica are in equilibrium with HF. 

The reaction is most probably initiated by radical attack of a reduced carbonyl function on the aromatic ring in the adjacent system. The product is formed as the radical anion but reoxidized by air during work-up. In the presence of proton donors, or in alcoholic solvents, reduction of 98 gives a mixture of acyclic and partly hydrogenated cyclic products [288]. Substituted 98, such as the 4,4, 5,5 -tetracarboxylic acid, gives coupling in basic alcoholic medium but not in DMF [289]. 

The mechanistic model, proposed by Breslow, has been extensively discussed [149]. The core of the benzoin reaction is the polarity reversal (umpolung) of the carbonyl, initiated by nucleophihc attack of NHC to the aldehyde yielding an acyl anion equivalent that triggers the carbon-carbon bond formation. The a-hydroxy ketone results from the addition of the acyl anion equivalent to another aldehyde (Scheme 16.21). 

The reaction involves the nucleophilic attack of a peracid anion on the unionized peracid giving a tetrahedral diperoxy intermediate that then eliminates oxygen giving the parent acids. The observed rate of the reaction depends on the initial concentration of the peracid as expected in a second-order process. The reaction also depends on the stmcture of the peracid (specifically whether the peracid can micellize) (4). MiceUization increases the effective second-order concentration of the peracid because of the proximity of one peracid to another. This effect can be mitigated by the addition of an appropriate surfactant, which when incorporated into the peracid micelle, effectively dilutes the peracid, reducing the rate of decomposition (4,90). 

Reaction Mechanism. The reaction mechanism of the anionic-solution polymerization of styrene monomer using n-butyllithium initiator has been the subject of considerable experimental and theoretical investigation (1-8). The polymerization process occurs as the alkyllithium attacks monomeric styrene to initiate active species, which, in turn, grow by a stepwise propagation reaction. This polymerization reaction is characterized by the production of straight chain active polymer molecules ("living" polymer) without termination, branching, or transfer reactions. 

The first step consists in the attack of a proton on the W-H bond to yield a labile dihydrogen intermediate (Eq. (3)) that rapidly releases H2 to form a coordi-natively unsaturated complex (Eq. (4)). This complex adds water in the next step to form an aqua complex (Eq. (5)) that completes the reaction by substituting the coordinated water by the X anion (Eq. (6)). Steps (3)-(6) are repeated for each W-H bond and the factor of 3 in the rate constants appears as a consequence of the statistical kinetics at the three metal centers. The rate constants for both the initial attack by the acid (ki) and water attack to the coordinatively unsaturated intermediate (k2) are faster in the sulfur complex, whereas the substitution of coordinated water (k3) is faster for the selenium compound. 

A mechanism proposed 87) for the alkaline hydrolysis of tetraethyl pyrophosphate, which is markedly accelerated by HPO e ions, has been substantiated by isotopic labeling 88). The nucleophilic attack by HPOJp on the symmetrical pyrophosphate 131 is considered to lead initially to the unsymmetrical P P1-diethyl pyrophosphate dianion 132 which decomposes spontaneously under the conditions of reaction to give the diethyl phosphate anion and POf 102. The latter reacts with water to form inorganic phosphate and with alcohols suclj as methanol and ethylene glycol to produce alkyl phosphates. 

Domino transformations combining two consecutive anionic steps exist in several variants, but the majority of these reactions is initiated by a Michael addition [1]. Due to the attack of a nucleophile at the 4-position of usually an enone, a reactive enolate is formed which can easily be trapped in a second anionic reaction by, for example, another n,(5-urisalurated carbonyl compound, an aldehyde, a ketone, an inline, an ester, or an alkyl halide (Scheme 2.1). Accordingly, numerous examples of Michael/Michael, Michael/aldol, Michael/Dieckmann, as well as Michael/SN-type sequences have been found in the literature. These reactions can be considered as very reliable domino processes, and are undoubtedly of great value to today s synthetic chemist... 

Under favourable circumstances, the initially formed /V-ylid reacts further through C-N cleavage. Thus, in the presence of a strong nucleophile, such as a phenoxide anion, the quaternary dichloromethylammonium cation forms an ion-pair with the phenoxide anion (Scheme 7.27), which decomposes to yield the alkyl aryl ether and the /V-formyl derivative of the secondary amine [22, 23]. Although no sound rationale is available, the reaction appears to be favoured by the presence of bulky groups at the 4-position of the aryl ring. In the absence of the bulky substituents, the Reimer-Tiemann reaction products are formed, either through the breakdown of the ion-pair, or by the more direct attack of dichlorocarbene upon the phenoxide anion [22,23],... 

Reaction of the azophosphoranes (Scheme 7.32) with dichlorocarbene follows an interesting pathway to produce l-aryl-5-chloropyrazole-3-carboxylic esters. The initial displacement of the phosphine (probably as the oxide) has been confirmed by the isolation of the 3,3-dichloropropenic ester under mild conditions. Subsequent conversion into the pyrazole appears to involve reaction with a trichloromethyl anion followed by attack by a second dichlorocarbene, although evidence for the mechanism of these steps is circumstantial [40],... 

The Claisen reaction may be visualized as initial formation of an enolate anion from one molecule of ester, followed by nucleophilic attack of this species on to the carbonyl group of a second molecule. The addition anion then loses ethoxide as leaving group, with reformation of the carbonyl group. 

Nucleophilic attack at substituted ring carbon is probably the most common reaction of 1,3,4-oxadiazoles. However, few examples have been reported of nucleophilic attack at unsubstituted carbon since such compounds (19a) are relatively uncommon. The mechanism of the well-known conversion of 2-amino-oxadiazoles (in aqueous alkali) into triazoles has been studied in the case of the reaction where (19a R = NHPh) is converted to (20). This proceeds via the anion of semi-carbazide PhNHCONHNHCHO and is initiated by hydroxide attack at C-5 <84JCS(P2)537>. A similar nucleophilic attack by hydroxide on oxadiazole (19a R = 5-pyrazolyl) was followed by cyclization to the pyrazolo-triazine (21). Hydrolytic cleavage of 2-ary 1-1,3,4-oxadiazoles to aroyl-hydrazides allows use of the former as protected hydrazides. Oxadiazole (19a R = 4-... 

Recently, Behiman and coworkers discussed the mechanism of the Elbs oxidation reaction and explained why the para product predominates over the ortho product in this oxidation. According to the authors, semiempirical calculations show that the intermediate formed by the reaction between peroxydisulfate anion and the phenolate ion is the species resulting from reaction of the tautomeric carbanion of the latter rather than by the one resulting from the attack by the oxyanion. This is confirmed by the synthesis of the latter intermediate by the reaction between Caro s acid dianion and some nitro-substituted fluorobenzenes. An example of oxidative functionalization of an aromatic compound is the conversion of alkylated aromatic compound 17 to benzyl alcohols 20. The initial step in the mechanism of this reaction is the formation of a radical cation 18, which subsequently undergoes deprotonation. The fate of the resulting benzylic radical 19 depends on the conditions and additives. In aqueous solution, for example, further oxidation and trapping of the cationic intermediate by water lead to the formation of the benzyl alcohols 20 (equation 13) . ... 

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