Brian G. Cox
- Published in print:
- 2013
- Published Online:
- May 2013
- ISBN:
- 9780199670512
- eISBN:
- 9780199670512
- Item type:
- book
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199670512.001.0001
- Subject:
- Physics, Condensed Matter Physics / Materials
Acids and bases are ubiquitous in chemistry. Our understanding of them, however, is dominated by their behaviour in water. Transfer to non-aqueous solvents leads to profound changes in acid-base ...
More
Acids and bases are ubiquitous in chemistry. Our understanding of them, however, is dominated by their behaviour in water. Transfer to non-aqueous solvents leads to profound changes in acid-base strengths and to the rates and equilibria of many processes: for example, synthetic reactions involving acids, bases, and nucleophiles; isolation of pharmaceutical actives through salt formation; formation of zwitter-ions in amino acids; and chromatographic separation of substrates. This book seeks to enhance our understanding of acids and bases by reviewing and analysing their behaviour in non-aqueous solvents. The behaviour is related where possible to that in water, but correlations and contrasts between solvents are also presented. Fundamental background material is provided in the initial chapters: quantitative aspects of acid–base equilibria, including definitions and relationships between solution pH and species distribution; the influence of molecular structure on acid strengths; and acidity in aqueous solution. Solvent properties are reviewed, along with the magnitude of the interaction energies of solvent molecules with (especially) ions; the ability of solvents to participate in hydrogen bonding and to accept or donate electron pairs is seen to be crucial. Experimental methods for determining dissociation constants are described in detail. In the remaining chapters, dissociation constants of a wide range of acids in three distinct classes of solvent are discussed: protic solvents, such as alcohols, which are strong hydrogen-bond donors; basic, polar aprotic solvents, such as dimethylformamide; and low-basicity and low-polarity solvents, such as acetonitrile and tetrahydrofuran. Dissociation constants of individual acids vary over more than twenty orders of magnitude among the solvents, and there is a strong differentiation between the response of neutral and charged acids to solvent change. Ion-pairing and hydrogen-bonding equilibria, such as between phenol and phenoxide ions, play an increasingly important role as the solvent polarity decreases, and their influence on acid–base equilibria and salt formation is described.Less
Acids and bases are ubiquitous in chemistry. Our understanding of them, however, is dominated by their behaviour in water. Transfer to non-aqueous solvents leads to profound changes in acid-base strengths and to the rates and equilibria of many processes: for example, synthetic reactions involving acids, bases, and nucleophiles; isolation of pharmaceutical actives through salt formation; formation of zwitter-ions in amino acids; and chromatographic separation of substrates. This book seeks to enhance our understanding of acids and bases by reviewing and analysing their behaviour in non-aqueous solvents. The behaviour is related where possible to that in water, but correlations and contrasts between solvents are also presented. Fundamental background material is provided in the initial chapters: quantitative aspects of acid–base equilibria, including definitions and relationships between solution pH and species distribution; the influence of molecular structure on acid strengths; and acidity in aqueous solution. Solvent properties are reviewed, along with the magnitude of the interaction energies of solvent molecules with (especially) ions; the ability of solvents to participate in hydrogen bonding and to accept or donate electron pairs is seen to be crucial. Experimental methods for determining dissociation constants are described in detail. In the remaining chapters, dissociation constants of a wide range of acids in three distinct classes of solvent are discussed: protic solvents, such as alcohols, which are strong hydrogen-bond donors; basic, polar aprotic solvents, such as dimethylformamide; and low-basicity and low-polarity solvents, such as acetonitrile and tetrahydrofuran. Dissociation constants of individual acids vary over more than twenty orders of magnitude among the solvents, and there is a strong differentiation between the response of neutral and charged acids to solvent change. Ion-pairing and hydrogen-bonding equilibria, such as between phenol and phenoxide ions, play an increasingly important role as the solvent polarity decreases, and their influence on acid–base equilibria and salt formation is described.
Brian G. Cox
- Published in print:
- 2013
- Published Online:
- May 2013
- ISBN:
- 9780199670512
- eISBN:
- 9780199670512
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199670512.003.0006
- Subject:
- Physics, Condensed Matter Physics / Materials
Basic polar aprotic solvents such as dimethylsulphoxide, dimethylformamide, and N-methylpyrrolidin-2-one are very poor at solvating anions, but interact strongly with cations and the proton in ...
More
Basic polar aprotic solvents such as dimethylsulphoxide, dimethylformamide, and N-methylpyrrolidin-2-one are very poor at solvating anions, but interact strongly with cations and the proton in particular. Their low autoionization constants are compatible with the use of very strong bases, thus allowing direct measurement of dissociation constants for an extensive range of weak acids: ketones, esters, nitroalkanes, nitriles, amides, anilines, and alcohols. Poor anion solvation results in dissociation constants of carboxylic acids and phenols that are typically several orders of magnitude lower than in water, and show much greater sensitivity to substituents. Extensive homohydrogen-bond formation is also observed for carboxylic acids and phenols. Protonated nitrogen bases show slightly higher acidities relative to those in water. Excellent correlations exist for pKa-values amongst the solvents and with aqueous values.Less
Basic polar aprotic solvents such as dimethylsulphoxide, dimethylformamide, and N-methylpyrrolidin-2-one are very poor at solvating anions, but interact strongly with cations and the proton in particular. Their low autoionization constants are compatible with the use of very strong bases, thus allowing direct measurement of dissociation constants for an extensive range of weak acids: ketones, esters, nitroalkanes, nitriles, amides, anilines, and alcohols. Poor anion solvation results in dissociation constants of carboxylic acids and phenols that are typically several orders of magnitude lower than in water, and show much greater sensitivity to substituents. Extensive homohydrogen-bond formation is also observed for carboxylic acids and phenols. Protonated nitrogen bases show slightly higher acidities relative to those in water. Excellent correlations exist for pKa-values amongst the solvents and with aqueous values.
Brian G. Cox
- Published in print:
- 2013
- Published Online:
- May 2013
- ISBN:
- 9780199670512
- eISBN:
- 9780199670512
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199670512.003.0002
- Subject:
- Physics, Condensed Matter Physics / Materials
Quantitative treatment of acid–base behaviour is presented, including the definition of acids, bases, and dissociation constants, and the important relationships between solution pH, acid strength, ...
More
Quantitative treatment of acid–base behaviour is presented, including the definition of acids, bases, and dissociation constants, and the important relationships between solution pH, acid strength, acid–base ratios, and species distribution. Molecular structural features of acids, which influence both the acid strengths and their dependence upon solvent, are summarized. They include the bond strength, the ability to stabilize anions and cations by charge dispersion, and the nature of the atom to which the proton is bonded. The acidity of carbon acids, which are widely used in synthetic procedures, is reviewed. Structural rearrangements on ionization of ketones, esters, and nitroalkanes, which allow the negative charge generated on ionization of the C-H bond to reside on oxygen, leads to greatly enhanced acidity. The inductive influence of strongly electron-withdrawing groups ? to the ionizing C-H bond is important for nitriles and sulphones.Less
Quantitative treatment of acid–base behaviour is presented, including the definition of acids, bases, and dissociation constants, and the important relationships between solution pH, acid strength, acid–base ratios, and species distribution. Molecular structural features of acids, which influence both the acid strengths and their dependence upon solvent, are summarized. They include the bond strength, the ability to stabilize anions and cations by charge dispersion, and the nature of the atom to which the proton is bonded. The acidity of carbon acids, which are widely used in synthetic procedures, is reviewed. Structural rearrangements on ionization of ketones, esters, and nitroalkanes, which allow the negative charge generated on ionization of the C-H bond to reside on oxygen, leads to greatly enhanced acidity. The inductive influence of strongly electron-withdrawing groups ? to the ionizing C-H bond is important for nitriles and sulphones.
Brian G. Cox
- Published in print:
- 2013
- Published Online:
- May 2013
- ISBN:
- 9780199670512
- eISBN:
- 9780199670512
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199670512.003.0007
- Subject:
- Physics, Condensed Matter Physics / Materials
Low-basicity and low-polarity aprotic solvents, including importantly acetonitrile and tetrahydrofuran, are poor at solvating both anions and cations. Dissociation constants are consequently very ...
More
Low-basicity and low-polarity aprotic solvents, including importantly acetonitrile and tetrahydrofuran, are poor at solvating both anions and cations. Dissociation constants are consequently very low, especially for neutral acids, typically 10–12 orders of magnitude lower than in basic aprotic solvents, such as dimethylsulphoxide, and up to 18 log units lower compared with water. Homohydrogen-bond formation involving carboxylic acids, phenols, and amines, and intramolecular hydrogen bonding in mono-anions of suitable dicarboxylic acids, is extensive. Ion-pair formation is modest except in the low-dielectric solvent tetrahydrofuran. In tetrahydrofuran, acid–base equilibria are dominated by ion association formation, even at concentrations as low as 10‐5 M. In consequence, ion-pair acidity scales, based on solvent-separated lithium ion-pairs or contact caesium ion-pairs have been developed. For carbon acids, the ion-pair acidities correlate well with absolute pKa-values in dimethylsulphoxide.Less
Low-basicity and low-polarity aprotic solvents, including importantly acetonitrile and tetrahydrofuran, are poor at solvating both anions and cations. Dissociation constants are consequently very low, especially for neutral acids, typically 10–12 orders of magnitude lower than in basic aprotic solvents, such as dimethylsulphoxide, and up to 18 log units lower compared with water. Homohydrogen-bond formation involving carboxylic acids, phenols, and amines, and intramolecular hydrogen bonding in mono-anions of suitable dicarboxylic acids, is extensive. Ion-pair formation is modest except in the low-dielectric solvent tetrahydrofuran. In tetrahydrofuran, acid–base equilibria are dominated by ion association formation, even at concentrations as low as 10‐5 M. In consequence, ion-pair acidity scales, based on solvent-separated lithium ion-pairs or contact caesium ion-pairs have been developed. For carbon acids, the ion-pair acidities correlate well with absolute pKa-values in dimethylsulphoxide.
