This is a worksheet lab there is no prelab write up required

Lab #1
Acid and Base Calculations; Solubility and Permeability of Organic Compounds
Review acid/base chemistry using class notes, your text, and Organic acid-base chemistry from Kahn
academy. There is a math help sheet also linked on the lab calendar page.
Turn in the last two pages of this workbook.

Acid/base equilibrium reactions. In this lab, you will explore Brnsted-Lowry acid/base theory
introduced in general chemistry. This theory defines an acid as a proton donor and a base as a proton
acceptor. Simply put, Brnsted theory is a way of thinking about an acid/base reaction in terms of
proton transfer equilibria. A generic example is given below where HA is any acid reacting with
water:

H-A

+
+

H2O

K eeqq

+
+

H 3O

Equation 1

The reaction shown above uses a special kind of double arrow that infers a relationship between the
reactants and products. This double arrow (
) denotes that the reactants are in equilibrium with the
products where the position of equilibrium is governed by the constant Keq which is unique to each
acid/base reaction. The value of Keq is given by the equation
Keq =

[H 3 O + ][ A ]
[HA ][H 2 O]

Equation 2

where the square brackets indicate the concentration of the substance involved. Since the
concentration of water remains essentially constant at 55.5M, equation 2 can be rearranged to give:

Keq [H 2O] =

[H 3O + ][ A ]
[HA]

Equation 3

The acid equilibrium constant K a for the acid HA is defined as

[H 3O + ][ A ]
Keq [H 2 O] = K a =
[HA ]

Equation 4

Example 1. The acid hydrogen chloride HCl is reacted with the base water to give hydronium ion and
chloride ion:
H
H

Cl

O
H

Cll

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Note the use of the convention to draw unequal equilibrium arrows where the longer arrow points to
the side favored at equilibrium. For this particular reaction, you should not be surprised that the
products are favored at equilibrium since you know HCl is defined as a strong acid (an acid that
almost completely dissociates to ions in water.) The value of K a for HCl is approximately 1 10 6 .
Example 2. Acetic acid is reacted with water to give hydronium ion and acetate ion:
H3C

H 3C

H
O

O
O
H

In this example, the double arrows indicate that equilibrium favors the reactant acid (the un-ionized
form.) Again, this should not be a surprise since you know acetic acid is a weak acid (an acid that does
not appreciably dissociate in water.) This means that when acetic acid and water are combined, very
little ionization occurs and equilibrium lies toward the reactants (on the left-hand side of the arrows.)
The value of K a for acetic acid is approximately 1.8 10 5 .
Many chemical reactions that are governed by equilibrium use this double arrow convention to indicate
whether equilibrium favors products, as in example 1, or reactants, as in example 2. For whatever acid
base reaction being evaluated, the acid dissociation constants Ka indicate the position of equilibrium
that is whether the equilibrium favors reactants or products. Look again at HCl reacting with water.
Since HCl nearly completely dissociates in water, concentrations of hydronium ion and chloride ion
(the products of dissociation) are much greater than the concentration of undissociated HCl.
Therefore, the K a of HCl will be greater than 1 since the numerator of the fraction that defines K a
will be much larger than the denominator. In contrast, for acetic acid where equilibrium favors nondissociated acid in water, the concentration of undissociated acid will be much higher and so the
denominator of the fraction that defines K a will be greater than the numerator. Thus, the K a for
acetic acid will be less than 1. While K a values are easily accessible, they tend to be unwieldy in
everyday use. A quick comparison of our examples shows this: The K a of HCl is about 1 10 6 while
the K a of acetic acid is about 1.8 10 5 . Since acid dissociation equilibria are so central to
understanding reactivity, chemists have developed a shorthand notation called pKa where the lowercase p denotes the negative logarithm. Logarithms are used to make the quantities much more
manageable. These pKa values are readily available in table form (see the course website) and provide
the same information as Ka. Such tables would show that the pKa of HCl is 6 and the pKa of acetic
acid is 4.76. Recall that log x determines the power to which 10 must be raised to arrive at x. Thus for
HCl, we would have log(1106) = 6, and so
pKa = log(1 10 6 ) = 6 .
For acetic acid, we would have log(1.8105) = 4.76, and so
pKa = log(1.810-5) = 4.76.

This is a worksheet lab there is no prelab write up required

When comparing the strengths of acids, remember the lower the pKa, the stronger the acid. For our
examples, HCls pKa of 6 is lower than acetic acids pKa of 4.76, so HCl is a stronger acid than acetic
acid.
Predicting the Position of Equilibrium in an Acid Base Reaction
We can use pKa values to determine the position of equilibrium in many acid/base systems. For
example, consider the acetic acid/ ammonia system below. Will equilibrium favor reactants or
products (acetate anion and ammonium cation)?
H3 C

H3 C

N
H

H
H

Consulting your pKa table, you will find that the acid (acetic acid) has a pKa of about 5 whereas the
conjugate acid (ammonium ion) has a pKa of about 10. In any acid/base reaction, the position of
equilibrium always favors reaction of the stronger acid (acetic acid) and stronger base to form the
weaker acid (ammonium cation) and weaker base. So in this example, the products will be favored at
equilibrium. When considering base strength, remember that the stronger acid always give the weaker
conjugate base).
pH and pKa. When we measure the pH of an aqueous solution, we are measuring the concentration of
hydronium ion (protonated water, a molecule made up of neutral water bonded to a proton.) Because
strong acids almost completely dissociate in water, they will increase the presence of protons in
solution (as H3O+.) While free protons (H+) do not exist in water, it has become tradition to use
protons and hydronium ion interchangeably in equilibrium expressions. Thus, the symbol pH is
used instead of p[H3O+].
Recall from equation 4 the definition of Ka:
[H 3O + ][ A ]
Ka =
[HA]

If we rearrange equation 4 to isolate [H3O+], we have

[ H 3O + ] = K a

[HA]
[A ]

If we take the base-ten logarithm of both sides, we have

log [H 3O + ] = log K a + log( [HA] /[ A ] )

Multiplying both sides by 1 gives us

log [H 3O + ] = log K a log( [HA] /[ A ] )

This is a worksheet lab there is no prelab write up required

or by using the fact that log( y / x) = log( x / y ) ,

log [H 3O + ] = log K a + log( [ A ] /[HA] )

Finally, since p is used for log, we obtain
pH = pKa + log( [ A ] /[HA] )

Equation 5

Equation 5 is known as the Henderson-Hasselback equation; this equation tells us that it is enough to
know the pH of a solution and pKa of the acid in order to determine the relative concentrations of the
acid HA and the ion A in solution at equilibrium. A quick rearrangement of equation 5 gives us
[A ]
= 10 ( pHpK a )
[HA ]

Equation 6

Suppose, for instance, that the pH equals the pKa. Then the right-hand side of equation 6 becomes
10 0 = 1 . This means that [A] = [HA] and so the concentrations of the acid and ion are equal. We can
conclude that 50% of the acid HA has disassociated.
The following table illustrates the amount of dissociation of an acid HA with a pKa = 4 in solutions of
various pH values:
pH
2
3
4
5
6

pKa
4
4
4
4
4

Ratio [A]/[HA]
0.01
0.1
1
10
100

Percentage of HA Dissociated
1%
9%
50%
91%
99%

So, for instance, at a pH of 3, very little of the acid dissociates (there are only 1/10 as many A ions as
there are HA molecules) while at a pH of 5, most of the acid dissociates (there are ten times as many
A ions as there are HA molecules.)
Biological pH and Acid Dissociation. Given that physiological pH is 7.3, we can use the Henderson
Hasselbalch equation to determine exact ratios ([A] / [HA]) of an acid in a cellular system. For
example, determine [A] / [HA] for a 0.0010 M solution of p-nitrophenol (pKa 7.2) at pH = 7.3.
Recall that
[A ]
[A ]
= 10 ( 7.37.2 ) = 1.26
= 10 ( pH pK a ) so
[HA]
[HA]
Rearranging gives [A] = (1.26) [HA] and substituting into [A] + [HA] = 0.0010M and solving two
simultaneous equations gives [A] = 0.00056M and [HA] = 0.00044 M

This is a worksheet lab there is no prelab write up required

Solvent Polarity. We need to think about how polarity affects a compounds solubility in aqueous and
organic solvents. First, an organic solvent is understood to be any liquid that is not water. Next, we
need to understand the distinctions between non-polar, protic, and polar aprotic solvents in addition to
the terms miscible and immiscible. We approach these terms by means of specific examples. Hexane,
an example of a non-polar solvent, is a liquid at room temperature with the molecular formula C6H14.
The experimentally determined density of hexane is 0.672 g/mL (less dense than water). Hexane is
immiscible with water; when vigorously mixed with water it will form an emulsion that quickly
separates into two layers, with hexane as the top layer (think of oil and vinegar salad dressing). Note
that hexane (a hydrocarbon) has only carbon-hydrogen covalent bonds. Further, the electronegativity
difference between carbon and hydrogen is slight, giving rise to non-polar covalent bonds. In terms of
solvents, hydrocarbons such as hexane are always considered to be non-polar.
Next, ethanol (CH3CH2OH), considered a protic solvent, is a short chained alcohol that is completely
miscible with water. This means that a mixture of ethanol and water does not separate into layers the
way a hexane-water mixture does. If you consult a table of pKa values, you will note that ethanol has a
pKa of about 16 whereas hydronium cation has a pKa of <0. That is to say,

H3C
CH2
O
base

CH2

O
H

H
H

O
H

H3C

acid
pKa = 16

conjugate acid
pKa -1.74

O
conjugate base

While a pKa of 16 is weak compared with a pKa of <0, alcohols are sufficiently acidic to be considered
protic solvents solvents able to act as Bronsted acids under sufficiently basic conditions. Certainly
ethanol is polar or it would not be miscible with water. Other protic solvents include water, amines,
acetic acid, formic acid, etc.
Finally, consider diethyl ether (CH3CH2OCH2CH3), considered a polar aprotic solvent. This
compound has a density of 0.807 g/mL, is immiscible with water, is a less polar solvent than ethanol,
but more polar solvent than hexane. Why is ether more polar than hexane? Consider the Lewis
structure of each. While hexane is composed of non-polar covalent bonds, diethyl ether on the other
hand has two carbon-oxygen covalent bonds. Since oxygen is more electronegative than carbon, these
will be polar covalent bonds so the molecule overall will be polar. However, ether does not contain an
acidic proton, hence it is classed as aprotic. Most non-polar solvents will be immiscible with water,
most protic solvents will (at least to some extent) be miscible with water, polar aprotic solvents may or
may not be miscible with water.
Solubility as a function of pKa. Solvent polarity and acid/base characteristics come together in the
phrase like dissolves in like. Here, this means less polar substances dissolve in less polar solvents
while more polar substances dissolve in more polar solvents. You will use this principle in your first
lab experiment to move a compound from a less polar organic solvent to more polar water. For
example, benzoic acid in its neutral (un-ionized) form is less polar than in its more polar charged form
called benzoate ion. Therefore, neutral benzoic acid will be more soluble in less polar organic solvents
(diethyl ether) than in water, whereas benzoate ion will be more soluble in the more polar solvent
water than in less polar organic solvents. Another way of thinking about this is when you ionize a
neutral acid to a charged base the charged base will look like water since it will then be very polar.

This is a worksheet lab there is no prelab write up required

benzoic acid
neutral f orm
not soluble in water

sodium benzoate
ionized f orm
soluble in water

OH

stronger acid

water

+ NaOH

stronger base

pKa = 4.2
less polar
all covalent bonds

weaker conjugate base

more polar
ionic bond

Na

+ H2O

weaker conjugate
acid
pKa 15.7

From before, we found that if we take a compound HA with a pKa of 4 and add it to an aqueous
solution at pH 6, most of it (at a 100/1 ratio) will be in the conjugate base (ionized) form A .
Furthermore, from our guiding principle of like dissolves like, A will dissolve in water. On the other
hand, if we put our compound with a pKa of 4 into an aqueous solution at pH 2, most of it will remain
as neutral HA and it will not dissolve. However, if we now add a non-miscible polar aprotic solvent to
generate a two phase system (aqueous/organic), HA will be soluble in the less polar organic solvent.
Again, for this to work, the organic solvent must not be miscible with water so to provide two phases
a more polar aqueous phase and a less polar organic phase. This is the principle you will use in lab
to separate mixtures of compounds with different pKas. This is illustrated in the next figure for an acid
with a pKa of 4.

Organic

Water

HA HA HA
HA
HA
HA HA
HA
HA
HA

pH = 3

HA

A A
A A A
A
A

A
A
A

pH = 5

Notice that when the pH of the aqueous phase is equal to 3, the acid dissociates only slightly (there is
10 times as much HA as there is A-.) and much more HA will be in the organic phase. Conversely,
when the pH of the aqueous phase is equal to 5, the acid dissociates readily (the concentration of A- is
10 times as much as that of HA.) The ionized form of the acid (A-) will be soluble in water but not in
the organic solvent.

This is a worksheet lab there is no prelab write up required

This same principle holds true for transport of chemicals across biological
membranes. Drugs are more likely to be absorbed into the body if they are neutral
since cell membranes are made mostly of organic compounds called lipids.
Not all compounds become charged when deprotonated. An example is an amine such as
diethylamine. Diethylamine is charged at low pH and neutral at a higher pH.
CH 2CH 3

CH 2 CH 3

CH 2CH 3

CH 2 CH 3
N

N
H
H

Diethyl ammonium ion form

predominates at lower pH

Diethyl amine neutral form

predominates at higher pH

The pKa of diethylammonium ion (protonated diethylamine) is 10.8. Most aliphatic amines have pKas
between 9 and 11, while aromatic amines such as aniline have much lower pKas of around 3 to 5.
Protonated aniline has a pKa of around 5.

This is a worksheet lab there is no prelab write up required

Acid and Base Calculations
Section #______

Name__________________

Date__________

TA __________________

Homework questionsinclude lone pairs on all heteroatoms (S, O and N) in your answers.
1.

Draw the structure of protonated aniline (anilinium ion) and its conjugate base aniline.

2.

Calculate the percentage of ionized and unionized forms present in the following solutions. Assume that
the given concentrations start completely unionized and then ionize to some ratio at the given pH. Show
your calculations:
a. 0.0010 M glycolic acid (pKa = 3.83) at pH = 4.50

b. 0.0020 M propanoic acid (pKa = 4.87) at pH = 5.30

Page 1

This is a worksheet lab there is no prelab write up required

3.

Complete the following three tasks below.

a. Find the approximate pKa value (you can estimate to the nearest 5) for each compound in the
table below and draw the structure of each compound and its conjugate base.
b. Circle the form (the acid or the base) that predominates at a pH of 7.
c. Write whether the predominate form would be more water soluble or more organically soluble.
(You do not need to show any calculations for this question)

Butyl Ammonium
pKa = ____

Octanol
pKa = ____

Carbonic Acid
pKa (1) = ____
pKa (2) = ____

acid

Decanoic Acid
pKa = ____

conjugate base

Conj. Base #1

Conj. Base #2

Phenol
pKa = ____

Pentane thiol
pKa = ____

conjugate base

acid

tertButanol
pKa = ____

Page 2

3-Hydroxypropanoic Acid

pKa = ____