Expt 2. Acid/Base Extraction and C-13 NMR.
Part 1 - Acid/Base Extraction
Relevant textbook readings – Nichols -
Organic Chemistry Lab Techniques, Chap 4, 5.6.(Chapter
references below are from this source.) Karty, Chapter 6
especially 6.3.
Background
In this experiment you will learn how to use a separatory
funnel for the purpose of carrying out liquid/liquid
extraction, a useful separation method commonly
referred to as just "extraction". The process of
extraction involves intimately mixing a solution with an
immiscible extraction solvent so as to allow compounds in
the solution to partition between the two liquid layers
that form after mixing is discontinued. Compounds that are
more soluble in the extraction solvent than in the
original solvent will end up predominantly in that layer,
whereas compounds that are less soluble will stay in the
original solvent. Water is almost always one of the
solvents with the other solvent being an organic compound
such as diethyl ether (CH3CH2OCH2CH3)
or dichloromethane (CH2Cl2), so the
two layers can be referred to simply as the aqueous layer
and the organic layer. Physical separation of the
layers then accomplishes the separation of the compounds
in the solution based on their solubility characteristics.
Acid/base extraction
(see Chapter 4.8) is a process that allows the separation
of organic acids, organic bases, and organic neutral
compounds (not an acid or base) from each other based on
the solubility differences of the organic acid (or base)
and its conjugate base (or conjugate acid). Organic acids
such as carboxylic acids (RCOOH), phenols (PhOH), and
thiols (RSH), all have an acidic proton that can be
deprotonated by aqueous base (usually NaOH) to form a salt
form of the acid, which is much more soluble in aqueous
solution than in organic solvents, as illustrated by
equation 1 for a carboxylic acid. Hence, the carboxylic
acid can be extracted from an organic solvent by aqueous
NaOH.
RCOOH + NaOH(aq) →
RCOO-Na+(aq) +
HOH (1)
The original carboxylic acid can be retrieved from the
aqueous layer by simply neutralizing the base with HCl(aq)
and reforming the carboxylic acid (eq 2). The relatively
insoluble carboxylic acid often precipitates at this point
and can be collected by vacuum filtration.
RCOO-Na+(aq)
+ HCl(aq) →
RCOOH(s) + NaCl(aq) (2)
Conversely, organic bases (e.g., amines, RNH2,
R2NH, or R3N) are protonated by
aqueous acid (usually HCl) to form salts that are much
more soluble in the aqueous layer (eq 3). Hence, amines
can be extracted from an organic solvent by aqueous HCl.
RNH2 + HCl(aq)
→ RNH3+Cl-(aq)
(3)
The original amine is retrieved by treating the aqueous
layer with aqueous base (NaOH) so as to deprotonate the
salt (eq 4), which often precipitates and can be collected
by vacuum filtration.
RNH3+Cl-(aq)
+ NaOH(aq) → RNH2(s)
+ HOH + NaCl(aq) (4)
Organic compounds that are neither acids or bases do not
react with either NaOH or HCl and, therefore remain more
soluble in the organic solvent and are not extracted.
Overview
You will use an acid/base extraction to separate a 1:1:1
mixture of trans-cinnamic acid, ethyl
4-aminobenzoate (benzocaine), and N,N-diethyl-3-toluamide
(DEET).
Pre-Lab
The mixture given includes an organic acid, an organic
base, and a (non-acid non-base) neutral compound. Identify
which is which and write equations for the reactions that
will occur when the mixture is extracted with HCl and then
later with NaOH. Also, make sure to include a
literature pKa value for the acid and pKb for the base in
your table of reactants and products.
Experimental Procedures
Pay special attention to the information in chapter 4 of
Nichols and to the instructions provided by the instructor
on the proper use of the separatory funnel. Also see https://www.youtube.com/watch?v=2A98YEKzsMI
for a nice video tutorial. It is strongly recommended that
you label all containers used to contain the various
layers separated and solids obtained.
For the numbered steps that follow please recognize that
there is no need to go strictly in sequence 1 --> 6.
For example a more efficient sequence of steps might be 1
--> 2 --> 5 --> 3 --> 6 --> 4. A flowchart
would work well in your prelab plan as a way of organizing
the tasks that need to be done.
- Dissolve 1.5 g of the provided mixture in 20 mL
dichloromethane (DCM).
- Acid extraction - Transfer the solution to a
separatory funnel, add 15 mL 1M HCl, stopper the funnel
and shake gently at first with frequent venting.
As it becomes clear that excessive pressure is not
building up, end by shaking vigorously for 30 s or more
and then allow the layers to separate. Into separate
Erlenmeyer flasks, drain off the bottom layer through
the stopcock and then pour out the top layer through the
top of the separatory funnel. Label the flasks as to
which is organic and which is aqueous and then return
the organic layer to the separatory funnel and and
extract it with another 15 mL of 1M HCl using the same
procedures as before. Combine the aqueous layers from
the first two extractions and return the organic layer
to the separatory funnel. Extract once more with 1M HCl,
combining the obtained aqueous layer with those obtained
previously. Label the combined aqueous layers as "HCl
extracts".
- Base extraction - Return the organic layer to the
separatory funnel and extract it with 15 mL of 1M NaOH.
Separate the layers as in part 2 and return the organic
to the funnel twice more extracting each time with an
additional 15 mL of 1M NaOH. Label the combined
aqueous layers as "NaOH extracts".
- Isolation of neutral substance - Add anhydrous sodium
sulfate to the flask containing the organic layer
and allow to stand for 10-15 minutes with
occasional swirling. Decant the liquid into a dry round
bottom flask. (This process is referred generally
referred to as "drying over Na2SO4"
- see the part on drying agents in Chapter 4.7.) Remove
the DCM solvent on the rotary evaporator (Chapter 5.6,
the instructor or TA will assist with this). Use a
Pasteur pipet to transfer as much of the obtained oily
liquid as possible into a vial. Weigh and save for week
2.
- Isolation of organic base - Carefully add 1M NaOH to
the flask containing the HCl extracts so as to
neutralize the pH. You can use pH paper to make sure the
solution is no longer acidic and/or you can use the
formation of precipitate as a gauge. The organic base is
only slightly soluble in water so it precipitates as it
is reformed from the salt by deprotonation. Thus,
maximum precipitate formation indicates complete
neutralization. Collect the formed solid by vacuum
filtration on a Buchner funnel. Weigh it and allow it to
air dry until week 2.
- Isolation of organic acid - Use 1M HCl to neutralize
the aqueous layer from the NaOH extractions. Do the
addition carefully and slowly. Also collect this solid
by vacuum filtration, weigh it and and allow to air dry
until next week.
Additional questions to address in the report
- The original mixture was prepared by using equal
masses of the three compounds. Use this information to
calculate the percent recovery of each compound. (The
proper word here is "recovery" not "yield" because no
net chemical reaction occurred. Instead we merely are
recovering the unchanged components of the mixture.)
- Use the pKa's of the acids on both sides of your
equations for the acid/base extraction reactions (see
prelab assignment) to calculate the equilibrium
constants for these reactions. Hint 1: the pKb of a base
and it's conjugate acid are related by the equation, pKa
+ pKb = 14. Hint 2: You will need to look up values for
the pKa of water and of HCl. Hint 3: You can use this
equation to calculate pKeq from pKa's: pKeq =
pKa(reactant) - pKa(product). What do your answers here
tell us about how much of the carboxylic acid and amine
should theoretically have reacted when reacted with
NaOH(aq) and HCl(aq) respectively?
- Look up solubilty data for the three compounds in the
original mixture and use it to comment on how much of
each was likely to have been lost in the discarded
aqueous wastes.
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