Extraction
• Pulling a compound (or compounds) out of one phase into another
Experiment 4: Extraction
solid/liquid ! making a cup of tea
liquid/liquid ! most common in lab
liquids must be immiscible
• Used for the isolation, purification, and/or separation of compounds
- isolation of potential therapeutics from natural sources
Part A: Separation of Acidic, Basic and Neutral Substances
Part B: Isolation & Analysis
- remove water soluble impurities from an organic reaction mixture
typically inorganic salts
means of preliminary purification (wash)
Reading: Mohrig, Hammond & Schatz
Ch. 11 pgs 113-132
Ch. 12 pgs 132-141
Ch. 20 pgs 277-310
- separate two organic compounds bearing different functional groups
• Terminology
- extract: pulling out what you want
- wash: removing what you don't want
Carey Ch. 13 pgs 574-581
both are effectively the same process
watch the technique video on the course website!
• This technique is based on solubility differences
Extraction: How Does it Work
Organic vs. Aqueous Layer: Top or Bottom?
• Consider the solvent density vs. water
• Organic compound in a separatory funnel with two immiscible liquids
- two layers
Densities of Some Common Extraction Solvents
- typically an organic solvent & water
solvent
- relative solvent densities will determine
which layer is which (e.g. top or bottom)
less dense
(top layer)
• Layers are mixed by inverting funnel gently;
will separate on standing
• Compound (x) will distribute (partition) itself
between the layers (phases)
- equilibrium based on rel. solubility of x in each layer
x x x x
x x x
x
less dense
layer
!
more dense
layer
- organic layer will contain neutral organic compounds
- aqueous layer will contain organic & inorganic salts
• Drain lower layer out the bottom;
Pour upper layer out the top
separatory funnel
more dense
(bottom layer)
density
hexanes
0.672
diethyl ether
0.713
benzene
0.879
water
1.000
saturated NaCl (aq)
1.198
dichloromethane
1.335
chloroform
1.498
"
• If don't know densities add a few drops of water to the separatory
funnel - water will join the aqueous layer!
Distribution Coefficient (K)
Extraction
• Extraction Efficiency:
- For an efficient extraction (water ! organic solvent), K ! 4
• Ratio of concentrations of a compound [X] in the layers is known the
distribution coefficient (K)
- If K < 1, will be difficult to extract the compound from water
K=
[X] in organic solvent
[X] in water
!
solubility of X in organic solvent
• What if extraction efficiency is poor??
- increase number of extraction steps
solubility of X in water
more efficient to carry out multiple small extractions than 1 large one
even if K ! 4
• If know solubility's, can calculate K
so 3 x 5mL extraction better than 1 x 15mL extraction!!
- saturate the aqueous layer with NaCl ("salting out")
If for compound X: solubility in water is 5g/100 mL
"solubility in an organic solvent is 35 g/100 mL
K=
35g/100mLB
5g/100mLA
=
0.35
shift the equilibrium (change K)
= 7
0.05
• How can we use extraction to separate two (or more) organic compounds?
- modify solubility?
K gives us information about extraction efficiency
General Principles
Separation of a Mixture by Extraction
# start with a mixture of compounds dissolved in an organic solvent #
Extract With
Removes
Why?
water
H2O
polar, low MW compounds
inorganic acids & bases
polar organics with <5 carbons
solubility
acid
HCl
basic compounds
inorganic bases
R-NH2
weak base
NaHCO3
strongly acidic compounds
inorganic acids
R-CO2H (pKa ! 5)
strong base
NaOH
Na2CO3
acidic compounds
OH
(pKa ! 10)
R NH2
O
R
HCl
H
R NH2
O
NaHCO3
R
OH
OH
NaOH
Cl
O
Na
O
Na
Drying Agents
Next Week
• Used to remove final traces of water from organic solutions
• Typically anhydrous, inorganic salts ! readily hydrate
• Typical drying agents include:
Capacity
Speed
Applications
calcium chloride
calcium sulfate
magnesium sulfate
Drying Agent
CaCl2
CaSO4
MgSO4
high
low
high
medium
fast
fast
potassium carbonate
sodium sulfate
K2CO3
Na2SO4
medium
high
medium
slow
hydrocarbons
generally useful
not for very acid
sensitive cmpds
not for acidic cmpds
generally useful
• Procedure
- add a small amount of solid drying agent to the organic solution
- swirl; drying agent should be free flowing (not clumped); avoid excess
- let stand (swirl occasionally) for 5-15 minutes
- filter or decant solution away from drying agent
Extraction Overview
1. Your mixture contains the following components (dissolve in ether)
(October 3 - 7)
Experiment 4: Extraction
A. Separation of a 3-Component Mixture by Extraction
strong organic acid - benzoic acid (carboxylic acid)
organic base - 4-chloroanaline (amine)
neutral substance - 1,4-dimethoxybenzene (ether)
B. Isolation & Analysis
recover compounds by neutralization/filtration or evaporation
evaluate success of separation by TLC & melting point
confirm identity of separated components by IR
Exp 4 Notebook: Research Plan MUST be a flowchart
use the entire page for the flowchart; experimental
section will follow on a new page
DUE:
Distillation Lab Report (exp 3)
Lab Reports are due at the beginning of your regular lab session
Extraction Technique: The Basic Setup
• separatory funnel set in a ring
(be sure it is the right size)
• stopper & stopcock should fit
avoid leaks
funnel (optional)
• stopcock should be closed!
2. Separation of the 4-chloroaniline (an amine) is achieved by extracting
the mixture with acid
Ar-NH2 + HCl ! Ar-NH3+ Cl 3. The benzoic acid (a carboxylic acid) is separated upon extraction with base
Ar-CO2H + NaOH ! Ar-CO2- Na+
4. The 1,4-dimethoxybenzene will remain in the organic layer
• collection flask below
"just in case"
metal ring
• add solution slowly
avoid spills - use a funnel
• solution must be cool
avoid large pressure build up
ring stand
stopper
stopcock should be
closed!!!
note that the tip of the
funnel is below the
rim of the flask!
empty flask
or beaker
Extraction Technique: Separation
Experimental Details
• add appropriate aqueous reagent to the solution
• Separation
• stopper the funnel and invert
hold on to the stopper!
1. Obtain approximately 1.5g compound mixture (1:1:1 ratio by weight)
- record accurate weight (does not need to be 1.50g!)
• vent carefully
release pressure; vent gases
point funnel away from yourself & others
CAUTION!
escaping gases
3. Add HCl to the separatory funnel; stopper and invert separatory funnel to mix
- be sure you know which layer is which!
- vent frequently to prevent pressure build-up
• repeat several times
DON'T SHAKE! avoid emulsions
• set funnel back into ring
4. Separate layers
- wait for separation to occur, then drain lower layer
! aqueous layer - will contain amine salt (flask #1)
- organic layer remains - will contain benzoic acid & 1,4-dimethoxybenzene
• allow layers to separate
be sure you know which layer is which!
• remove stopper
so funnel will drain!
• drain lower layer through stopcock
keep tip of funnel below rim of container
• pour upper layer out through top
avoid contamination
2. Dissolve in ether ! transfer resulting solution to the separatory funnel
- use a little extra solvent to complete transfer
hold stopper
securely!
Experimental Details
6. Add NaOH to separatory funnel; stopper and invert sep funnel to mix
- mix thoroughly -- deprotonation of benzoic acid is a bit slow
5. Repeat steps 3-4
- to ensure complete extraction of the amine from the organic layer
- REMEMBER: multiple extractions using smaller amounts of reagent
are more efficient than a single extraction with the same reagent volume!
Experimental Details
• Isolation of Components
Flask 3:
organics; dry over anhydrous Na2SO4
swirl to mix; should be some free-flowing solid
- more is not better
- let sit for 5-10 min (keep busy while you wait!)
decant liquid into tared roundbottom flask
concentrate using the rotary evaporator
- no sand baths! Fire Hazard!
- HINT: place flask with organics in back of hood and do
something else while you wait for the rotavap!
Flask 1:
acidic extracts; make basic with concentrated NaOH (check pH)
7. Separate layers as before
- wait for separation to occur, then drain lower layer
! aqueous layer - will contain carboxylic acid salt (flask #2)
- organic layer remains - will contain 1,4-dimethoxybenzene
8. Repeat steps 6 & 7
- to ensure complete extraction of the carboxylic acid from the organic layer
9. Wash organic layer with saturated NaCl (aq)
- preliminary drying
- drain lower layer out through bottom (set aside to discard later)
- pour top layer out through top of sep funnel (flask #3)
! will contain 1,4-dimethoxybenzene
Ar-NH3+ Cl - + NaOH ! Ar-NH2 ($)
cool & collect crystals
Flask 2:
basic extracts; make acidic with concentrated HCl (check pH)
Ar-CO2- Na+ + HCl ! Ar-CO2H ($)
cool & collect crystals
Experimental Details
Some Pointers:
• Finishing Up
• Label your flasks!
- one Erlenmeyer/beaker looks pretty much like the next
1. dry samples
- samples #1 & 2 will be very wet; first press between two pieces of filter
paper, then dry under vacuum (be sure side arm test tube is
clean!!)
• NEVER throw anything away until you're absolutely sure you don't need it
- you can always dispose of it later
- once discarded, it's tough to get it back!
2. weigh samples (& calculate % recovery)
- how much of each compound can you expect to recover?
• When extracting, invert funnel gently - don't shake
- keeps emulsions from forming
- emulsions will take a long time before layers separate
3. determine melting point of each compound
• Vent frequently
- avoid pressure build up - sep funnel could explode
4. evaluate success of separation by TLC
- spot initial 1:1:1 mixture, plus 3 isolated components
- developing solvent is chloroform (use in the hood!)
- how can you tell if separation was successful?
• During isolation, be sure solutions are acidic/basic (check with pH paper)
- do NOT dip paper into solution; use a boiling stick or glass rod
- MIX THOROUGHLY after each addition of HCl or NaOH
5. Get IR spectra from your TA
- use to confirm identity of each component
• Come prepared
- easy to get confused if you're not clear on what you're doing
- must write a flow sheet for the pre-lab research plan
(use the entire width of the page)
Infrared Spectroscopy (IR)
Infrared Spectroscopy
• Infrared region of electromagnetic spectrum
": 2,500-16,000 nm
#: 1.9 x 1013 - 1.2 x 1014 Hz
• Absorption in specific region in IR spectrum corresponds to specific types
of molecular vibrations:
FREQUENCY (cm-1)
4000
• Photon energies associated with this region are weak
- not large enough to excite electrons
- can induce vibrational excitation of covalently bonded atoms & groups
3600
3200
H
C
H
C
H
H
H
symmetric
stretch
asymmetric
stretch
scissoring
(in plane bending)
2000
1800
1600
tr ip l e
bon ds
1400
1200
do ubl e
bon ds
O-H, N- H
1000
800
600
fi nge rp ri nt
re gi on
C= O
C !C, C !N
C-C, C-O, C- N, etc .
C !O, et c .
• Wide variety of vibrational motions; commonly talk about "stretching & bending"
e.g. for C-H bond
H
2400
Bon ds t o H
• Exact frequencies of vibrations determined by the strength of the bonds
involved and the masses of the connected atoms
C
2800
C=C
C= N
C-H
2.5
3.0
3.5
4.0
5
6
(MICRON S )
Ar-H
7
8
9
10
11 12 13 14
16
Infrared Spectroscopy
Identification of Mixture Components
• Plot light absorbsed/transmitted as a function of frequency, can determine
what types of functional groups are present in a molecule
Distinguishing features by IR spectroscopy (see Carey, pg 579)
• Carboxylic acids
- broad OH stretch (ca. 3000 cm-1) - may be diffuse
- C=O stretch (ca. 1710 cm-1)
• Amines
- NH stretch (ca. 3400 cm-1) - 2 bands for a NH2 group
C-H stretch
IR spectrum of tert-butylbenzene
• Ethers
- none of the above
- will likely see minor FG absorbances
C-H stretch (ca. 2850-3150 cm-1)
C-O stretch (ca. 1000-1250 cm-1)
- minor absorbances will be present in acid & amine spectra as well
SDBS Database National Institute of Advanced Industrial Science and Technology; 11/7/07
Infrared Spectrum of a Carboxylic Acid
O
R
Infrared Spectrum of an Amine (RNH2)
R-NH2
OH
NH stretch
OH stretch
C=O stretch
%
NO C=O
Infrared Spectrum of an Ether
OR
Writing the Lab Report: Exp #3 Distillation
! Purpose
- technique experiment: what will you learn?
- what conclusions will you reach?
- a general discussion of theory/expected results is not a purpose!
will show minor FG absorbances only
! Results & Discussion
- Plot data for both simple & fractional distillations (include graphs)
these are essentially temp vs time plots as discussed in class
raw data (# drops vs temperature) does not belong here!
- Evaluate data ! simple distillation
discuss temp vs. volume graph (equiv to temp vs. time!)
compare to theory (what do you expect to see)?
C-H stretch
C-O stretch
%
%
NO NH
NO C=O
e.g. what does the temperature change indicate?
are the drops pure? does purity vary?
report % recovery and % holdup
Writing the Lab Report: Exp #3 Distillation
! Results & Discussion
- Evaluate data ! fractional distillation
discuss same topics as for simple distillation
- Compare the two distillation techniques
compare how well the two components separated in each case
what data can you use?
do your results agree with your expectations? explain!
what does plot tell you about composition of drops over time?
bp recorded vs known bp
Temp vs. Vol plots
discuss differences in % holdup and % recovery
relates to the efficiency of the two processes
- Decide which method is better for the separation of cyclohexane & toluene
clearly explain why you made this choice (based on your results)
do your findings agree with your expectations?
again, first must decide what you expect to see
your expectations shouldn't influence interpretation of your data
Writing the Lab Report: Exp #3 Distillation
! Conclusion
- a brief recap of your findings
- make a general statement about distillation techniques you studied
- should be brief (2-3 sentences)
! Appendix A: Calculations
- Percent Recovery
% recovery =
amount distillate recovered (mL)
amount of original solution (mL)
x 100
- Percent Holdup
amount of material retained by the distillation apparatus
% holdup =
amount liquid left in flask(mL)
amount of original solution (mL)
x 100