Acids & Bases in Organic Chemistry

Acid / base properties are very important in Organic Chemistry. The loss of a proton is one means to generate a new carbon-carbon bond, so you need to know the pK_a for various types of X-H bonds. This will allow you to predict the outcome of many organic reactions.

Brønsted-Lowry Acids

There are several definitions for what an acid or base is. We will start our discussion with Brønsted-Lowry acids and bases.

Brønsted-Lowry define acids as a molecule which can donate a proton (H⁺). A base is an atom or molecule which can accept a proton. (Note: this imposes the criteria that a base must have a lone pair of electrons to "accept" the proton.) They react together to produce a conjugate base, the deprotonated form of the acid, and conjugate acid, the protonated form of the base.

The generic reaction equation for an acid and base is shown below.


Since the ability of a molecule to donate a proton depends on the molecular structure, a more specific description of the structure is important to understand the complex equilibria involved in acid-base reactions and organic chemistry.

Structurally a Brønsted-Lowry acid can be any atom (or atom within a molecule) that is bonded to a hydrogen atom by a σ-bond. The formal charge on the H atom is most often positive (+1) or neutral (0) and very rarely negative (-1). The overall charge of the molecule can be zero or negative as seen in polyprotic acids such as carbonic acid (bicarbonate) or sulfuric acid (hydrogen sulfate).


In contrast a Brønsted-Lowry base can be any atom (or atom in a molecule) with an unshared or non-bonding pair of electrons. This lone pair of electrons is indictaed in Lewis structures as two dots near the basic atom. The formal charge on this basic atom is most often neural or negative (rarely positive), however, a negative charge does not guarantee that it will be reactive. Anions such as nitrate, bromide, chloride and even sulfate are very stable and unreactive as bases for structural reasons discussed below.

Quantifying Acid Strength (K_a and pK_a)

"Strong acid - strong base goes to weak acid - weak base" is the classic definition of Brønsted-Lowry acid-base chemistry as explained in General Chemistry courses. Unfortunately that definition is too simplistic for wide application in organic chemistry. The proton transfer mechanisms seen in acid-base reactions are rapid and reversible and are best described as equilibrium processes where the protons are in a never-ending transfer between competing lone pair electrons on different molecules. It is difficult to describe the acid-base chemistry in absolute terms since there are a large number of acids and bases and reactivities are similiar for apparently diverse structures.

A structural definition of acid strength is more valuable in gaining a useful problem solving prespective while removing the absolutes implied by the terms strong and weak which might be modified to better emphasize the equilibrium nature of acid-base reactions. Thus, in terms of structure, a "stronger" acid is one where the atom whose σ-bond to the hydrogen atom is more polarized and hence more easily dissociated, and hence upon reaction the conjugate base's new lone-pair will be more delocalized (diffuse) and hence more difficult to reprotonate. Conversely, a "stronger" base is an atom whose lone-pair is more localized (focused) making it capable of attracting a proton, and hence upon reaction the conjugate acid's new σ-bond to the hydrogen atom is more difficult to dissociate. The reaction between an acid and a base can be represented mechanistically as:


where the two red mechanism arrows (bond-to-atom and lone-pair-to-atom) denotes a basic lone-pair that is attracted to an acidic H atom, as well as the dissociation of the acid's σ-bond with the release of the electrons to form the lone-pair on the conjugate base. The equal length arrows would emply that the equilibrium reaction lies in the middle, or approximately equal amounts or produces and reactants. Of course unequal equilbrium reactions exist, the following reaction favours the prodcuts, as indicated by the unsymmetric equilibrium arrows:


while the following reaction now favours the reactants.


Note the change in sign for the enthalpy of the reaction, ΔH. The first reaction proceeds from the strong(er) acid and strong(er) base to the weak(er) conjugate acid and weak(er) conjugate base, accompanied by the release of energy. The reverse reaction would also be possible but now moving from weak(er) acid and base to strong(er) acid and base and hence the enthaply is positive.

The description of the relative strength of an acid is given by the pK_a which will gauge the likelihood that a reaction will occur. The reaction commonly refers to aqueous solution where the acid or conjugate acid will dissociate producing the conjugate base or base and hydronium (H₃O⁺). The pH (concentration of hydronium) can be easily determined by experimental methods.


Since known concntrations of acid are added and the conjugate base (or base) is produced in a 1:1 ratio with hydronium, the equilibrium constant for the dissociation of the proton, defined as the K_eq can be determined as:


Although one would normally include all of the products in the equilibrium expression, in this case the solvent water is in vast excess to the other chemicals so that its concentration effectively remains constant at 55 mol/L or 55 M. Since it is unaffect by the reaction it is removed from the denominator by multipling both sides of the expression by the concentration of water resulting in the K_a:


Strong acids dissociate completely in water resulting in large K_a values, see the Table below for some common acids and their K_a and pK_a values. Weak acids on the otherhand dissociate only to a limited amount and the concentrations can be very small. As a result it is common to use the pK_a for comparison.


pK_a values are used widely in organic chemistry to determine whether acid-base reactions occur by comparing the strength of the acid and conjugate acid. The product side of the reaction will be favoured when the acid is stronger that the conjugate acid (the acid has the lower pK_a value). The reactant side of the reaction will be favoured when the conjugate acid has the lower pK_a.

Common Acids and their Conjugate base
acid		base		Ka	pKa
name	formula	formula	name
perchloric acid	HClO4	ClO4-	perchlorate	1.0 x 1010	-10
hydroiodic acid	HI	I-	iodide	3.2 x 109	-9.51
hydrobromic acid	HBr	Br-	bromide	1.0 x 109	-9.00
hydrochloric acid	HCl	Cl-	chloride	1.3 x 108	-8.12
sulfuric acid	H2SO4	HSO4-	bisulfate	1.0 x 103	-3.00
hydronium	H3O+	H2O	water	5.0 x 101	-1.70
nitric acid	HNO3	NO3-	nitrate	2.4 x 101	-1.38
chloric acid	HClO3	ClO3-	chlorate	1.0 x 101	-1.00
oxalic acid	HO2C2O2H	HO2C2O2-	hydrogen oxalate	5.4 x 10-2	1.27
sulfurous acid	H2SO3	HSO3-	bisulfite	1.3 x 10-2	1.89
chlorous acid	HClO2	ClO2-	chlorite	1.1 x 10-2	1.96
bisulfate acid	HSO4-	SO42-	sulfate	1.0 x 10-2	2.00
phosphoric acid	H3PO4	H2PO4-	dihydrogen phosphate	7.1 x 10-3	2.15
nitrous acid	HNO2	NO2-	nitrite	7.2 x 10-4	3.14
hydrofluoric acid	HF	F-	fluoride	6.6 x 10-4	3.18
formic acid	HCO2H	HCO2-	formate	1.8 x 10-4	3.74
hydrogen selenide	H2Se	HSe-	hydroselenide	1.3 x 10-4	3.89
benzoic acid	C6H5COOH	C6H5OO-	benzoate	6.3 x 10-5	4.20
hydrogen oxalate	HO2C2O2-	-O2C2O2-	oxalate	5.4 x 10-5	4.27
hydrazoic acid	HN3	N3-	azide	2.5 x 10-5	4.60
acetic acid	CH3COOH	CH3OO-	acetate	1.8 x 10-5	4.74
carbonic acid	H2CO3	HCO3-	bicarbonate	4.4 x 10-7	6.36
hydrogen sulfide	H2S	HS-	hydrosulfide	1.1 x 10-7	6.96
dihydrogen phosphate	H2PO4-	HPO42-	hydrogen phosphate	6.3 x 10-8	7.20
bisulfite	HSO3-	SO32-	sulfite	6.2 x 10-8	7.21
hypochlorous acid	HClO	ClO-	hypochlorite	2.9 x 10-8	7.54
hydrocyanic acid	HCN	CN-	cyanide	6.2 x 10-10	9.21
ammonium	NH4+	NH3	ammonia	5.8 x 10-10	9.24
boric acid	H3BO3	H2BO3-	dihydrogen borate	5.8 x 10-10	9.24
bicarbonate	HCO3-	CO32-	carbonate	4.7 x 10-11	10.33
hydrogen phosphate	HPO4-	PO43-	phosphate	4.2 x 10-13	12.38
dihydrogen borate	H2BO3-	HBO32-	hydrogen borate	1.8 x 10-13	12.74
hydrosulfide	HS-	S2-	sulfide	1.3 x 10-13	12.88
hydrogen borate	HBO32-	BO33-	borate	1.6 x 10-14	13.80
water	H2O	HO-	hydroxide	1.8 x 10-16	15.74
methanol	CH3OH	CH3O-	methoxide	3.2 x 10-16	15.49
hydrogen	H2	H-	hydride	1.0 x 10-36	36.00
ammonia	NH3	NH2-	nitride/amide	1.0 x 10-38	38.00
methane	CH4	CH3-	methide	1.0 x 10-48	48.00

Examples:

The results of these K_a and pK_a determinations can provide a perspective on the magnitude of the equilibria.

A Strong Acid

Consider hydrochloric acid (HCl), the acid dissociation reaction is shown below:




The K_a and pK_a values of 1 x10⁸ and -8 respectively result from measuring a pH equating to a 10,000:1 ratio of dissociated acid to un-ionized HCl. In other terms the "odds" of finding an un-ionized molecule of HCl are 1 in 10,000. In these terms a "strong acid" can be quantitatively described as a solution with a very high probability of coming in contact with a proton dissociated from the acid.

A Weak Acid

A weaker carboxylic acid (acetic acid CH₃CO₂H) can be considered the same way:




The K_a and pK_a values of 1.58 x10^-5 and 4.8 respectively result from measuring a pH equating to a 1:63,095 ratio of dissociated acid to un-ionized acetic acid. In other terms the "odds" of finding an un-ionized molecule of HCl are 63,095 in 1. In these terms a "weak acid" can be quantitatively described as a solution with a very low probability of coming in contact with a proton dissociated from the acid.

A Very Weak Acid

Compare this now to the very weak acid of an alcohol (methanol (CH₃OH) which can be considered the same way:




The K_a and pK_a values of 3.2 x10^-16 and 15.49 respectively describe a solution where the odds of finding a dissociated proton are extremely small at 1 in 312,500,000,000,000 or 1:3.125¹⁵, this is smaller than identifying one single human on the entire planet, it is less than identifying one single star in the Milky Way galaxy.

An Extremely Weak Acid

Compare this now to the extremely weak acid of an alkane (2-methylpropane (CH₃)₃CH) which can be considered the same way:




The K_a and pK_a values of 1 x10^-53 and 53 respectively describe a solution where the odds of finding a dissociated proton are vanishingly small at 1 in 100,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000 or 1:10⁵³, the is MUCH smaller than all of the stars in the universe.