Protic solvents solvent coordination

In a Lewis-acid catalysed Diels-Alder reaction, the first step is coordination of the catalyst to a Lewis-basic site of the reactant. In a typical catalysed Diels-Alder reaction, the carbonyl oxygen of the dienophile coordinates to the Lewis acid. The most common solvents for these processes are inert apolar liquids such as dichloromethane or benzene. Protic solvents, and water in particular, are avoided because of their strong interactions wifti the catalyst and the reacting system. Interestingly, for other catalysed reactions such as hydroformylations the same solvents do not give problems. This paradox is a result of the difference in hardness of the reactants and the catalyst involved... 

For the other broad category of reaction conditions, the reaction proceeds under conditions of thermodynamic control. This can result from several factors. Aldol condensations can be effected for many compounds using less than a stoichiometric amount of base. Under these conditions, the aldol reaction is reversible, and the product ratio will be determined by the relative stability of the various possible products. Conditions of thermodynamic control also permit equilibration among all the enolates of the nucleophile. The conditions that permit equilibration include higher reaction temperatures, protic solvents, and the use of less tightly coordinating cations. 

For example, the substituted aniline Ar-NH2 (Ar = />-CH3OC6H4) reacts with the ruthenium nitrosyl complex Ru(bpy)2(Cl)(NO)2+ (bpy = 2,2 -bipyridine) to give a complex of the diazo ligand, namely Ru(bpy)2(Cl)(NNAr)2+ (57). Upon employing the 15N labeled nitrosyl complex Ru(bpy)2Cl(15NO)2+ this reaction resulted in the 15N coordinated product, Ru(bpy)2Cl(15NNAr)2+, demonstrating that the reaction occurs within the metal complex coordination sphere. When the reactions were conducted in non-protic solvents, these nucleophile-nitrosyl adducts could be isolated. 

Simon, J. D. and Doolen, R. On the dimensionality of the reaction coordinate of intramolecular charge-transfer reactions in protic solvents, J.Am. Chem.Soc., 114 (1992), 4861-4870... 

Product 34 predominates in the polar aprotic solvent (acetonitrile), while in the polar protic solvent (methanol) products 35 are formed preferentially. The different products are caused by the relative rate of deprotonation against desilylation of the aminium radical, that is in turn governed by the action of enone anion radical in acetonitrile as opposed to that of nucleophilic attack by methanol. In an aprotic, less silophilic solvent (acetonitrile), where the enone anion radical should be a strong base, the proton transfer is favoured and leads to the formation of product 34. In aprotic solvents or when a lithium cation is present, the enone anion radical basicity is reduced by hydrogen bonding or coordination by lithium cation, and the major product is the desilylated 35 (Scheme 4). 

The second important solvent effect on Lewis acid-Lewis base equilibria concerns the interactions with the Lewis base. Since water is also a good electron-pair acceptor129, Lewis-type interactions are competitive. This often seriously hampers the efficiency of Lewis acid catalysis in water. Thirdly, the intermolecular association of a solvent affects the Lewis acid-base equilibrium242. Upon complexation, one or more solvent molecules that were initially coordinated to the Lewis acid or the Lewis base are liberated into the bulk liquid phase, which is an entropically favourable process. This effect is more pronounced in aprotic than in protic solvents which usually have higher cohesive energy densities. The unfavourable entropy changes in protic solvents are somewhat counterbalanced by the formation of new hydrogen bonds in the bulk liquid. 

Polar protic solvents also possess a pronounced ability to separate ion pairs but are less favorable as solvents for enolate alkylation reactions because they coordinate to both the metal cation and the enolate ion. Solvation of the enolate anion occurs through hydrogen bonding. The solvated enolate is relatively less reactive because the hydrogen-bonded enolate must be disrupted during alkylation. Enolates generated in polar protic solvents such as water, alcohols, or ammonia are therefore less reactive than the same enolate in a polar aprotic solvent such as DMSO. 

Enolate ions, which are usually strong nucleophiles, are more important in preparative applications than are the enols. In additions to carbonyl groups, the carbon end, rather than the oxygen end, attacks but in SA,2 substitutions on alkyl halides, significant amounts of O-alkylation occur. The more acidic compounds, such as those with the j3-dicarbonyl structure, yield enolates with the greater tendency toward O-alkylation. Protic solvents and small cations favor C-alkylation, because the harder oxygen base of the enolate coordinates more strongly than does the carbon with these hard Lewis acids.147... 

A major development in this area was brought about by the invention of crosslinked polystyrene-supported 9-(/)-chlorobenzoy 1 )quinine ligands 17 [54] and 18 [55], The salient feature of this invention is the connection of the quinine unit to the polymer backbone through a sterically undemanding spacer. Thereby, the quinuclidine, which in catalysis coordinates to osmium, is free of steric interaction with the polymeric side chain. Dihydroxylation of trans-stilbene in the presence of 17 and NMO as co-oxidant gave stilbene diol with 87% ee. However, changing the terminal oxidant to K3[Fe(CN6)] led to full inhibition of the reaction. This result was explained by a possible collapse of the polymer in the required protic solvent, which prevented substrate penetration. 

The neutral A1H3 molecule formed when an A1H4 ion acts as a hydride donor is a Lewis acid that coordinates to the negatively charged oxygen atom in the product of this reaction. When, in a second step, a protic solvent is added to the reaction, an alcohol is formed. 

A protic solvent such as methanol (e - 32.6), renders HC1, HBr, and H2S04 all strong monobasic acids. Furthermore, protic solvents are uniquely advantageous, since the facile release of a proton upon coordination of a solvent molecule (Scheme 11) results in protons being consumed only in the neutralization of liberated phosphine. 

The solvent also influences the luminescence intensity and the largest enhancement was achieved with dmso or dmf, which are known to coordinate strongly to Lnm ions and thus favor the removal of water molecules from the first coordination sphere. Smaller enhancements were observed when ethanol or a protic solvent was used. The amount of solvent used for producing the suspensions is also crucial and the authors showed that the maximal luminescence intensity occurs for a concentration of the solvent of 20 vol%, above which the suspension decomposes thus leading to decreasing intensities. 

Ca, Sr, and Ba carboxylate, thiocarboxylate, thiocarboxylate-carboxylate, sulfito, and sulfonate compounds and their monodentate base adducts are white solids, many of which decompose on melting and are only soluble in protic solvents such as alcohols and water.I68-232-240 They are invariably oligomeric or polymeric in the solid state see, for example, Refs. 235, 239, and 240. On thermolysis, the nonfluorinated carboxylates degrade to the metal carbonates while their fluorinated congeners usually form the metal fluorides.212 222-262 269 The thiocarboxylates give mixtures of the metal oxides and sulfates on thermolysis in air.238-239 270 The methyl-thiocarbonate compound, Ca[(OCS)OMe]2(MeOH)3 2, is a dimer in the solid state, soluble in polar coordinating solvents and stable under reduced... 

You met borohydride in Chapter 6, where we discussed the mechanism of its reactions. Sodium borohydride will reduce only in protic solvents (usually ethanol, methanol, or water) or in the presence of electrophilic metal cations such as Li+ or Mg2+ (LiBH4 can be used in THF, for example). The precise mechanism, surprisingly, is still unclear, but follows a course something like this with the dotted lines representing some association, perhaps coordination or bond formation. 

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