Relative acidity, of alcohols

Figure 6-13 6-311+G vs. Experimental Aqueous-Phase Relative Acidities of Alcohols, Phenols and Related Compounds...

The delocalization of electron density in the conjugate base of an acid enhances its acidity, as indicated by the relative acidities of alcohols and carboxylic acids. While O—H bonds are heterolytically broken in both cases, only carboxylic acids yield delocalized anions. This subject is presented in adequate detail in most organic chemistry texts (Hine, 1975 March, 1977 Lowry and Richardson, 1981), so only a few examples that illustrate the significance of this phenomenon are presented here. 

Reactions Involving the O-H Bond of Alcohols and Phenols A. Relative Acidities of Alcohols and Phenols... 

Several factors determine the relative acidity of alcohols, including resonance, induction, and solvating effects. 

Alcohol Substitution. In the early period of normal thiol production, the normal alcohols were utilized as feedstocks. The use of a strong acid catalyst results in the formation of a significant amount of secondary thiol, along with other isomers resulting from skeletal isomerization of the starting material. This process has largely been replaced by uv-initiation because of the higher relative cost of alcohol vs alkene feedstock. 

Another example of the effect of resonance is in the relative acidity of carboxylic acids as compared to alcohols. Carboxylic acids derived from saturated hydrocarbons have ipK values near 5, whereas saturated alcohols have pA values in the range 16-18. This implies that the carboxylate anion can accept negative charge more readily than an oxygen on a saturated carbon chain. This can be explained in terms of stabilization of the negative charge by resonance, ... 

In the discussion of the relative acidity of carboxylic acids in Chapter 1, the thermodynamic acidity, expressed as the acid dissociation constant, was taken as the measure of acidity. It is straightforward to determine dissociation constants of such adds in aqueous solution by measurement of the titration curve with a pH-sensitive electrode (pH meter). Determination of the acidity of carbon acids is more difficult. Because most are very weak acids, very strong bases are required to cause deprotonation. Water and alcohols are far more acidic than most hydrocarbons and are unsuitable solvents for generation of hydrocarbon anions. Any strong base will deprotonate the solvent rather than the hydrocarbon. For synthetic purposes, aprotic solvents such as ether, tetrahydrofuran (THF), and dimethoxyethane (DME) are used, but for equilibrium measurements solvents that promote dissociation of ion pairs and ion clusters are preferred. Weakly acidic solvents such as DMSO and cyclohexylamine are used in the preparation of strongly basic carbanions. The high polarity and cation-solvating ability of DMSO facilitate dissociation... 

Reactant and product structures. Because the transition state stmcture is normally different from but intermediate to those of the initial and final states, it is evident that the stmctures of the reactants and products should be known. One should, however, be aware of a possible source of misinterpretation. Suppose the products generated in the reaction of kinetic interest undergo conversion, on a time scale fast relative to the experimental manipulations, to thermodynamically more stable substances then the observed products will not be the actual products of the reaction. In this case the products are said to be under thermodynamic control rather than kinetic control. A possible example has been given in the earlier description of the reaction of hydroxide ion with ester, when it seems likely that the products are the carboxylic acid and the alkoxide ion, which, however, are transformed in accordance with the relative acidities of carboxylic acids and alcohols into the isolated products of carboxylate salt and alcohol. 

Shortly after, the same authors reported the results on the relative acidities of 144 as compared with 1,3-dithiacycloheptane (150) and the open-chain model bis-(vinylthio)methane (151)m. In refluxing /erf-butyl alcohol-d in the presence of... 

The effects of exchange depends on the relative acidities of the alcohol (or other protonic substance) and the polymeric alcohol. The exchange reaction occurs throughout the course of the polymerization if the acidities of the two alcohols are approximately the same. The polymerization rate is unaffected while the molecular weight decreases (Eq. 7-15), but the molecular weight distribution (MWD) is Poisson. 

It was shown that the patterns of the relative rates of reaction of DPC and DPC with alcohols are essentially identical and followed the relative acidity of the alcohols (MeOH > /-PrOH > f-BuOH) and showed a kinetic deuterium isotope effect on reaction with the OH bond (Table 9.13). These results indicate that DPC attacks the O—H bond rather than the C—H bond of the alcohol. If the C—H bonds of the alcohol were attacked by DPC, as in the ground triplet state reaction, then one would expect 2-propanol would react faster than methanol. Lack of any dis-cernable quenching of DPC by diethyl ether and THF indicates that DPC ... 

Problem 13.23 Explain the relative acidity of liquid 1°, 2°, and 3° alcohols. 

As an example, let us consider the effect on acidity of substituting one hydrogen of HaO by various organic groups. Table 3.6 presents the available data for relative acidities of the simple alcohols in solution, whereas Table 3.7 shows the relationships in the gas phase. On the basis of the solution data alone, one would conclude that substitution by successively more bulky groups causes a steady lowering of acidity, although the relative positions of water and methanol... 

Rablen chose fcrf-butanol as the reference system, arguing that C-C bonds are less polar than C-H bonds and thereby eliminates polarization effects that may be inherent in smaller alcohol reference molecules, like methanol or ethanol. The proton exchange shown in Reaction 3.3 defines the relative acidities of acetic acid versus t rt-butanol. Using the CBS-Q method, acetic acid is 27.9 kcal mol" more acidic than t rt-butanol. 

Enols (pATa ca = 11-12) are usually more acidic than alcohols [e.g. EtOH pATa (H2O) = 15.9 ] but are less acidic than phenols [e.g. PhOH pATa(H20) = 9.95 ]. The acidity of enols (and the basicity of the corresponding enolate) is surprisingly uniform when considering the relative acidity of the carbonyl derivative. The majority of enols derived from saturated aldehydes and ketones have pATa ca 11-12. For simple aldehydes and ketones, such as acetaldehyde (45) and acetone (45 ), their enol acidity (pATa ) in water is similar even when their keto acidity (pATa ) is moderately different. It is interesting to note that relative enol stability (pATs) plays little or no role in the relative acidity of enols for example, as is the case of 45 and 45. ... 

Problem 1.9 Predict the relative acidity of (a) methyl alcohol (CH30H) and methylamine (CH3NH2) (b) methyl alcohol (CH3OH) and methancthiol (CH3SH) ... 

For acyclic compounds the regioselectivity depends upon statistical factors and the relative acidities of the different 3-hydrogens, the elimination preferring to take place towards the most acidic hydrogen. This can also influence the regioselectivity of elimination from alicyclic compounds, e.g. the a,3-unsatu-rated carbonyl compound (14) was obtained from the 3-aminocarbonyl compound (13), and the allylic alcohol (16) was the major product obtained on oxidation and pyrolysis of the hydroxyamine (15). ... 

Besides ethanol, large quantities of ethyl ether are produced by the sulfuric acid absorption process from ethylene. In the hydration of ethylene by this method the relative proportions of alcohol and ether obtained are determined by the temperature and concentration of the sulfuric acid solution at the hydration and recovery stage. The more dilute the acid, the higher the proportion of alcohol formed and vice versa. This same process has been applied to the formation of isopropyl ether from propene and this product is now available in tank car lots. 

Reaction Energies and the Relative Acidities of Carboxylic Acids and Alcohols. 

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