Water nucleophilic reactions with

Cobalt(II) complexes of three water-soluble porphyrins are catalysts for the controlled potential electrolytic reduction of H O to Hi in aqueous acid solution. The porphyrin complexes were either directly adsorbed on glassy carbon, or were deposited as films using a variety of methods. Reduction to [Co(Por) was followed by a nucleophilic reaction with water to give the hydride intermediate. Hydrogen production then occurs either by attack of H on Co(Por)H, or by a disproportionation reaction requiring two Co(Por)H units. Although the overall I easibility of this process was demonstrated, practical problems including the rate of electron transfer still need to be overcome. " " ... 

Nucleophilic reactions with water 77 Reactions with water as a base 87 Reactions of nucleophiles other than water 90 Reactivity, selectivity, and transition state structure 105 Hard and soft nucleophiles 110 Summary and conclusions 112 Acknowledgments 114 References 114... 

It might seem surprising that a nucleophilic reaction with water competes with proton loss from the phenanthrenonium ion considering the stability of the aromatic product. As discussed by Richard24 (and considered further below) this reflects a higher intrinsic reactivity of the cations toward nucleophilic attack which compensates for the thermodynamic disadvantage of this reaction. For the phenanthrenonium ion the ratio of rate constants for deprotonation and nucleophilic attack on the cation (kp/kH2o) is 25 25 for the 1-protonated naphthalene it is 1600,106 for 9-protonated anthracene, 1.8.75... 

Comparisons of structurally related hydroxy- and methoxy-substituted cations show that hydroxy is more stabilizing by between 4 and 5 log units. This difference was recognized 20 years ago by Toullec who compared pifas for protonation of the enol of acetophenone and its methyl ether145 (-4.6 and 1.3, respectively) based on a cycle similar to that of Scheme 15, but with the enol replacing the hydrate, and a further cycle relating the enol ether to a corresponding dimethyl acetal and methoxycarbocation.146 Toullec concluded, understandably but incorrectly, that there was an error in the pA a of the ketone (over which there had been controversy at the time).147,148 In a related study, Amyes and Jencks noted a difference of 105-fold in reactivity in the nucleophilic reaction with water of protonated and O-methylated acetone and concluded that the protonated acetone lacked a full covalent bond to... 

By contrast, measurement of pATR = 4.7 for the Fe(CO)3-cooordinated cyclo-hexadienyl cation 44 (Scheme 26) indicates a 107-fold more favorable equilibrium constant for carbocation formation than for the uncoordinated cation.197 However, a more dramatic effect of coordination is to render nucleophilic reaction with water more favorable than loss of a proton. A pXa = 9 can be estimated by computing the energy differences between coordinated and uncoordinated benzene and coordinated cyclohexadiene. This compares with the value of —24.5 for the uncoordinated cyclohexadienyl cation. The large difference must reflect the unfavorable effect of Fe(CO)3 coordination on benzene, an effect analogous to that found by Mayr for Fe (CO)3 coordination on the tropylium ion.196 As expected, both the coordinated cyclohexadienyl and tropylium ions are highly stereoselective toward exo attack by water. 

Richard has also shown that intrinsic barriers for carbocation reactions depend not only on the extent of charge delocalization but to what atoms the charge is delocalized. In a case where values of pifR for calculation of A were not available, comparisons of rate constants for attack of water kH2o with equilibrium constants for nucleophilic reaction with azide ion pKAz for 65-67 showed qualitatively that delocalization to an oxygen atom leads to a lower barrier than to an azido group which is in turn lower than to a methoxyphenyl substituent.226... 

Reactions of carbocations with water as a base removing a [3-proton to form an alkene or aromatic product have been less studied than nucleophilic reactions with water. Nevertheless, the correlations included in Fig. 1 (p. 43) represent a considerable range of measurements and these can be further extended to include loss of a proton a to a carbonyl group.116 Indeed, if one places these reactions in the wider context of proton transfers, it can be claimed that they constitute the largest of all groups of reactions for which correlations of rate and equilibrium constants have been studied.116,244,245... 

The amide 2 is paracetamol, the popular analgesic. Amines are much more nucleophilic than phenols (compare the basicities of ammonia and water) so reaction with acetic anhydride gives... 

The Hantzsch synthesis produces a reduced pyridine but there are many syntheses that go directly to pyridines. One of the simplest is to use hydroxylamine (NH2OH) instead of ammonia as the nucleophile. Reaction with a 1,5-diketone gives a dihydropyridine but then water is lost and no oxidation is needed. 

Reactions with Water, Alcohols, Phenols and Other Hydroxy Compounds. Car-bodiimides undergo nucleophilic reactions with a wide variety of nucleophiles. The polar forms of carbodiimides 431 and 432 demonstrate the nucleophilicity of the N-atoms as well as the electrophilicity of the center carbon atom. 

The initial species used in sol-gel processing are metal alkoxides (M(OR)y). Hydrolysis of metal alkoxides involves nucleophilic reactions with water as follows ... 

Trapping the carbonyl compound 1 in Scheme 3.3 with various nucleophiles provides various catalytic oxidative transformations of alcohols. When a primary or secondary amine is employed as a nucleophile, intermediate 13 undergoes nucleophilic reaction with amine to give iminium ion complex 14 along with water. Intramolecular hydride transfer of 14 gives the corresponding N-alkylated amine 15 with regen-... 

The presented reactions can be described as reductions of BTSC. They show that BTSC indeed behaves analogously to water in reactions with nucleophiles and/or reductive agents. The question whether these reactions are also mechanistically similar is difficult to answer based on the presented results. The LUMO of BTSC, which dictates the attack of a nucleophile according to the frontier orbital theory, is located at the central C atom as a ti -orbital. In contrast, the LUMO of the water molecule is the o -orbital. In a very simple approach, such reactions may be described as proton transfers. Similarly, it is possible that in BTSC the trimethylsilyl group is attacked nucleophilicaUy. 

In Table 8 rates of nucleophilic reactions with p-nitrophenyl acetate in water are collected. It should be kept in mind that relative reactivities vary with solvent. For example, in aqueous dioxane the relative reactivity of pyridine, as compared with acetate, towards acetic anhydride drops by many powers often as the solvent becomes less aqueous (Koskikallio, 1963). In 50 %, 25 %, 8 %, 2 %, and 0-4 % aqueous dioxane the ratio of pyridine reactivity to acetate reactivity is 14,0-34, 9-5 x 10 , 2-4 X 10 and < 3 x 10 , respectively. 

The higjily water-soluble dienophiles 2.4f and2.4g have been synthesised as outlined in Scheme 2.5. Both compounds were prepared from p-(bromomethyl)benzaldehyde (2.8) which was synthesised by reducing p-(bromomethyl)benzonitrile (2.7) with diisobutyl aluminium hydride following a literature procedure2.4f was obtained in two steps by conversion of 2.8 to the corresponding sodium sulfonate (2.9), followed by an aldol reaction with 2-acetylpyridine. In the preparation of 2.4g the sequence of steps had to be reversed Here, the aldol condensation of 2.8 with 2-acetylpyridine was followed by nucleophilic substitution of the bromide of 2.10 by trimethylamine. Attempts to prepare 2.4f from 2.10 by treatment with sodium sulfite failed, due to decomposition of 2.10 under the conditions required for the substitution by sulfite anion. 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

This reaction is useful in the preparation of anionic derivatives from the chlorides when the nucleophilic displacement route is unsatisfactory. Even weak acids, eg, phenols, mercaptans, and cycHc nitrogen compounds, can be made to undergo reaction with triorganotin hydroxides or bisoxides if the water of reaction is removed a2eotropicaHy as it forms. 

Aziridinones undergo two types of selective ring opening by nucleophiles <68AG(E)25). Reaction with proton-containing nucleophiles, e.g. water, alcohols, thiols, amines and mineral acids, leads exclusively to amides (339), corresponding to an C —N bond rupture. 

Pyrido[3,4-d]pyrimidine-2,4-dione synthesis, 3, 215 Pyridopyrimidines, 3, 201 iV-alkylations, 3, 206 biological activity, 3, 260-261 1-electron reductions, 3, 207 IR spectra, 3, 204 mass spectra, 3, 204 MO calculations, 3, 204 NMR, 3, 202, 203 nucleophilic substitution, 3, 213 8-nucleosides synthesis, 3, 206 physical properties, 3, 201-205 protonation, 3, 206 radical reactions, 3, 215 reactions with water, 3, 207 reduced... 

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