Water as a nucleophile

The mechanism which could explain the formation of these products is described in Scheme 27. In an EC mechanism, the intermediate radical cation 48a could undergo a follow-up reaction with water as a nucleophile to form radical 48b which could than dimerize through S-N or S-S bond formation or react with 48a to yield 50 and 51 as the fianl one-electron oxidation products. In an ECE mechanism, intermediate 48b is further oxidized to 48c which reacts with acetonitrile as a solvent to give 49 as the final two-electron oxidation product. The cation intermediate 48c can react with the parent molecule 48 through [2 -f 3]-cycloaddition to give the final products 50 and 51. The [2 -f 3]-... 

Benzene radical-cation is formed at the anode and reacts with water as a nucleophile to form phenol as an intermediate. Phenol is more readily oxidised than benzene and is converted to 1,4-dihydroxybenzene. Further oxidation of this in the anode chamber leads to quinone. 

The starting point for most discussions of reactivity is a correlation of rate and equilibrium constants. One such correlation is shown in Fig. 1 of this chapter. It applies not to reactions of the carbocation with water as a nucleophile but to water acting as base, that is, the removal of a [3-proton from the carbocation to form an alkene or aromatic product. We will consider this reaction below, but here note that for most of the carbocations in Fig. 1 values of kH2o> the rate constants for reaction of the carbocation with water as a nucleophile are also available.25... 

A notable difference between reactions of carbocations with water as a nucleophile and a base is the significantly higher intrinsic barrier for the latter. This difference has been demonstrated most explicitly by Richard, Williams, and Amyes22,246 for reaction of the a-methoxyphenethyl cation 68 with methanol (rather than water) acting as the base and nucleophile. The two reactions and the intrinsic barriers calculated from their rate and equilibrium constants are shown in Scheme 32. Values of A = 6.8 and 13.8 kcal mol 1 are found for the substitution and elimination, respectively. 

Fig. 6 A plot of log (kp/ku2o) for reactions of secondary (O) and tertiary ( ) carbocations with water as a nucleophile and base against pA H,o for hydration of the 7i-bond of the deprotonation product (points close to or above the dashed line correspond to reactions for which deprotonation leads to an aromatic product).

In the case of water as a nucleophile, the initially produced hydroxyimine may tauto-merise to an amide, which in turn generates a carboxylic acid upon further hydrolysis. Hydrolysis of a nitrile is, of course, one of the standard classical methods for the synthesis of carboxylic acids (Fig. 4-7). 

The survey in Figure 7.1 has already shown that nucleophiles can add to nitriles and thus produce carboxylic acid derivatives. Water as a nucleophile either undergoes clean addition to nitriles, and thus produces primary amides (corresponding to a partial hydrolysis of the nitrile ), or it continues with hydrolyzing the amides in situ to give carboxylic acid or carb-oxylate, which would amount to a total hydrolysis of the nitrile ... 

Hydroxide ion is seldom used as a nucleophile with unactivated secondary halides and never with tertiary halides because of competing E2 elimination reactions. For such compounds, replacement of the halide with OH can be accomplished by using water as a nucleophile and SN1 conditions ... 

This method could be successfully applied for a straightforward synthetic approach to 2,5,7,10-tetraoxabicyclo[4.4.0]decanes [256]. Some direct [257] and indirect [258] evidence has been found supporting attack of water as a nucleophile at the a-carbon, a reaction mode already identified for enol acetate radical cations [226,227], although this may not be general. 

The acid-catalyzed hydrocarboxylation of alkenes (the Koch reaction) can be performed in a number of ways. In one method, the alkene is treated with carbon monoxide and water at 100-350°C and 500-1000-atm pressure with a mineral acid catalyst. However, the reaction can also be performed under milder conditions. If the alkene is first treated with CO and catalyst and then water added, the reaction can be accomplished at 0-50°C and 1-100 atm. If formic acid is used as the source of both the CO and the water, the reaction can be carried out at room temperature and atmospheric pressure.The formic acid procedure is called the Koch-Haaf reaction (the Koch-Haaf reaction can also be applied to alcohols, see 10-77). Nearly all alkenes can be hydrocarboxylated by one or more of these procedures. However, conjugated dienes are polymerized instead. Hydrocarboxylation can also be accomplished under mild conditions (160°C and 50 atm) by the use of nickel carbonyl as catalyst. Acid catalysts are used along with the nickel carbonyl, but basic catalysts can also be employed. Other metallic salts and complexes can be used, sometimes with variations in the reaction procedure, including palladium, platinum, and rhodium catalysts. The Ni(CO)4-catalyzed oxidative carbonylation with CO and water as a nucleophile is often called Reppe carbonylationP The toxic nature of nickel... 

When the spiro-activated cyclopropane (479) is heated with aqueous acetone a 9 1 mixture of the lactone (482) and the dicarboxylic acid (480) is obtained. Thus, with water as a nucleophile, ring cleavage is faster than acylal cleavage. Presumably, the spiroacylal functions as an active ester in the cyclization of the initially formed 1,5-adduct (481) (equation 164) °. ... 

Water as a Nucleophile. Trace sulfenic acid formation may occur by thiolsulfinate reacting with water. 

Bimolecular preassociation mechanism with water as a nucleophile. 

There is also, of course, a term for water as a nucleophile. 

The Williamson Ether Synthesis is not the only ether preparation available, and it is not suitable for sterically crowded ethers. Ethers can also be synthesized by the addition of an alcohol to an alkene. Just as hydration of an alkene gives an alcohol product (water as a nucleophile installs an OH group), addition reactions in the presence of an alcohol gives an ether product (alcohol as a nucleophile installs an OR group). Two examples are shown below the alkene can react initially with either a strong acid or a mercury cation (alkoxymercuration-demercuration). 

El elimination is usually accompanied by a competing SnI substitution reaction that involves the same carbocation intermediate. Since both reaction mechanisms are reversible in this case, and since the alkene product gases are easily removed from the reaction, the competing substitution reaction (which predominantly regenerates the starting alcohol by attack of water, as a nucleophile, at the carbocation) is not troublesome and the equilibrium eventually leads to gas evolution. 

In aqueous solution the actinide cations interact with the solvent water. This hydration is a special case of complex ion formation with water as a nucleophilic ligand. The hydrated ions act as acids, splitting off protons from the water molecules of the hydration shell. Their acidity increases with the charge on the central atom. The divalent ions are weak acids. On account of their large radii, the... 

For this ketonization reaction, f-BuOOFl is a more selective oxidant than O2, however. For instance, 1-octene is oxidized under these conditions by i-BuOOH in benzene to 1-octanone in 98% yield in 10 minutes at 20°C. The oxidation of internal olefins is impossible except if they are conjugated with a carbonyl. It is also possible to use an alcohol or an amine instead of water as a nucleophile, which leads to an ether or amine. This version, particularly useful for the intramolecular formation of cyclic compounds, is illustrated below ... 

Water is so extensively used in catalytic oxidation reactions that usually this fact is regarded as a natural feature and remains unnoticed. Wacker oxidation of olefins by palladium complexes involves water as a nucleophilic reagent, and thus the whole Wacker-type chemistry, which has developed into a powerful and versatile method of organic synthesis, is derived from aqueous catalysis [178]. The role of the nature of the co-oxidant and the mechanism of deactivation of the palladium catalyst due to aggregation and growth of inactive metal particles were recently investigated, and such study may have relevance for other processes catalyzed by phosphine-less palladium catalysts [179]. 

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