Extraction

Experiment 4: Extraction

Pulling a compound (or compounds) out of one phase into another solid/liquid ! making a cup of tea liquid/liquid ! most common in lab liquids must be immiscible Used for the isolation, purication, and/or separation of compounds

Part A: Separation of Acidic, Basic and Neutral Substances Part B: Isolation & Analysis

- isolation of potential therapeutics from natural sources - remove water soluble impurities from an organic reaction mixture typically inorganic salts means of preliminary purication (wash) - separate two organic compounds bearing different functional groups Terminology - extract: pulling out what you want - wash: removing what you don't want both are effectively the same process This technique is based on solubility differences

Reading: Mohrig, Hammond & Schatz Ch. 11 pgs 113-132 Ch. 12 pgs 132-141 Ch. 20 pgs 277-310 Carey Ch. 13 pgs 574-581 watch the technique video on the course website!

Extraction: How Does it Work

Organic compound in a separatory funnel with two immiscible liquids - two layers - typically an organic solvent & water - relative solvent densities will determine which layer is which (e.g. top or bottom) 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 - 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 x x x x x x x x
less dense layer more dense layer

Organic vs. Aqueous Layer: Top or Bottom?

Consider the solvent density vs. water Densities of Some Common Extraction Solvents solvent
less dense (top layer)

density 0.672 0.713 0.879 1.000 1.198 1.335 1.498 "

hexanes diethyl ether benzene

water saturated NaCl (aq)

more dense (bottom layer)

dichloromethane chloroform

If don't know densities add a few drops of water to the separatory funnel - water will join the aqueous layer!

Distribution Coefcient (K)

Ratio of concentrations of a compound [X] in the layers is known the distribution coefcient (K) [X] in organic solvent [X] in water solubility of X in organic solvent solubility of X in water

Extraction
Extraction Efciency: - For an efcient extraction (water ! organic solvent), K ! 4 - If K < 1, will be difcult to extract the compound from water

K=

What if extraction efciency is poor?? - increase number of extraction steps more efcient to carry out multiple small extractions than 1 large one even if K ! 4 so 3 x 5mL extraction better than 1 x 15mL extraction!! - saturate the aqueous layer with NaCl ("salting out") shift the equilibrium (change K) How can we use extraction to separate two (or more) organic compounds? - modify solubility?

If know solubility's, can calculate K If for compound X: solubility in water is 5g/100 mL "solubility in an organic solvent is 35 g/100 mL 35g/100mLB 5g/100mLA 0.35 0.05

K=

= 7

K gives us information about extraction efciency

General Principles
# start with a mixture of compounds dissolved in an organic solvent # Extract With water H2O acid HCl Removes polar, low MW compounds inorganic acids & bases polar organics with <5 carbons basic compounds inorganic bases R-NH2 strongly acidic compounds inorganic acids R-CO2H (pKa ! 5) acidic compounds
OH
O R OH

Separation of a Mixture by Extraction

Why? solubility

R NH2

HCl

H R NH2

Cl

weak base NaHCO3 strong base NaOH Na2CO3

NaHCO3 R

O O Na

OH

NaOH

Na

(pKa ! 10)

Drying Agents
Used to remove nal traces of water from organic solutions Typically anhydrous, inorganic salts ! readily hydrate Typical drying agents include:
Drying Agent calcium chloride calcium sulfate magnesium sulfate potassium carbonate sodium sulfate CaCl2 CaSO4 MgSO4 K2CO3 Na2SO4 Capacity high low high medium high Speed medium fast fast medium slow Applications hydrocarbons generally useful not for very acid sensitive cmpds not for acidic cmpds generally useful

Next Week

(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/ltration or evaporation evaluate success of separation by TLC & melting point conrm identity of separated components by IR Exp 4 Notebook: Research Plan MUST be a owchart use the entire page for the owchart; experimental section will follow on a new page DUE: Distillation Lab Report (exp 3)

Procedure - add a small amount of solid drying agent to the organic solution - swirl; drying agent should be free owing (not clumped); avoid excess - let stand (swirl occasionally) for 5-15 minutes - lter or decant solution away from drying agent

Lab Reports are due at the beginning of your regular lab session

Extraction Overview
1. Your mixture contains the following components (dissolve in ether)

Extraction Technique: The Basic Setup

separatory funnel set in a ring (be sure it is the right size) stopper & stopcock should t avoid leaks stopcock should be closed! collection ask below "just in case" add solution slowly avoid spills - use a funnel solution must be cool avoid large pressure build up
ring stand stopper metal ring stopcock should be closed!!! note that the tip of the funnel is below the rim of the ask! empty ask or beaker funnel (optional)

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

Extraction Technique: Separation

add appropriate aqueous reagent to the solution stopper the funnel and invert hold on to the stopper! vent carefully release pressure; vent gases point funnel away from yourself & others repeat several times DON'T SHAKE! avoid emulsions set funnel back into ring 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

Experimental Details
Separation
CAUTION! escaping gases

1. Obtain approximately 1.5g compound mixture (1:1:1 ratio by weight) - record accurate weight (does not need to be 1.50g!) 2. Dissolve in ether ! transfer resulting solution to the separatory funnel - use a little extra solvent to complete transfer 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 4. Separate layers - wait for separation to occur, then drain lower layer ! aqueous layer - will contain amine salt (ask #1) - organic layer remains - will contain benzoic acid & 1,4-dimethoxybenzene 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 efcient than a single extraction with the same reagent volume!

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 7. Separate layers as before - wait for separation to occur, then drain lower layer ! aqueous layer - will contain carboxylic acid salt (ask #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 (ask #3) ! will contain 1,4-dimethoxybenzene

Experimental Details
Isolation of Components Flask 3: organics; dry over anhydrous Na2SO4 swirl to mix; should be some free-owing solid - more is not better - let sit for 5-10 min (keep busy while you wait!) decant liquid into tared roundbottom ask concentrate using the rotary evaporator - no sand baths! Fire Hazard! - HINT: place ask with organics in back of hood and do something else while you wait for the rotavap! acidic extracts; make basic with concentrated NaOH (check pH) 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

Flask 1:

Experimental Details
Finishing Up 1. dry samples - samples #1 & 2 will be very wet; rst press between two pieces of lter paper, then dry under vacuum (be sure side arm test tube is clean!!) 2. weigh samples (& calculate % recovery) - how much of each compound can you expect to recover? 3. determine melting point of each compound 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? 5. Get IR spectra from your TA - use to conrm identity of each component

Some Pointers:
Label your asks! - one Erlenmeyer/beaker looks pretty much like the next 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! When extracting, invert funnel gently - don't shake - keeps emulsions from forming - emulsions will take a long time before layers separate Vent frequently - avoid pressure build up - sep funnel could explode 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 Come prepared - easy to get confused if you're not clear on what you're doing - must write a ow sheet for the pre-lab research plan (use the entire width of the page)

Infrared Spectroscopy (IR)

Infrared region of electromagnetic spectrum ": 2,500-16,000 nm #: 1.9 x 1013 - 1.2 x 1014 Hz Photon energies associated with this region are weak - not large enough to excite electrons - can induce vibrational excitation of covalently bonded atoms & groups Exact frequencies of vibrations determined by the strength of the bonds involved and the masses of the connected atoms Wide variety of vibrational motions; commonly talk about "stretching & bending" e.g. for C-H bond
H C H

Infrared Spectroscopy
Absorption in specic region in IR spectrum corresponds to specic types of molecular vibrations:
FREQUENCY (cm-1) 4000 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600

Bon ds t o H

tr ip l e bon ds

do ubl e bon ds

fi nge rp ri nt re gi on

O-H, N- H C !C, C !N C !O, et c . C-H

C= O C-C, C-O, C- N, etc .

C=C C= N

Ar-H

H C H
C

H H

2.5

3.0

3.5

4.0

6 (MICRON S )

10

11 12 13 14

16

symmetric stretch

asymmetric stretch

scissoring (in plane bending)

Infrared Spectroscopy
Plot light absorbsed/transmitted as a function of frequency, can determine what types of functional groups are present in a molecule

Identication of Mixture Components

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 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

IR spectrum of tert-butylbenzene
SDBS Database National Institute of Advanced Industrial Science and Technology; 11/7/07

Infrared Spectrum of a Carboxylic Acid

O R OH

Infrared Spectrum of an Amine (RNH2)

R-NH2

OH stretch C=O stretch

NH 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! ! 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-O stretch do your results agree with your expectations? explain! what does plot tell you about composition of drops over time? e.g. what does the temperature change indicate? are the drops pure? does purity vary? report % recovery and % holdup

will show minor FG absorbances only

C-H stretch

% NO NH

% NO C=O

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? bp recorded vs known bp Temp vs. Vol plots

Writing the Lab Report: Exp #3 Distillation

! Conclusion - a brief recap of your ndings - 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

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

- Percent Holdup amount of material retained by the distillation apparatus

amount liquid left in flask(mL) amount of original solution (mL)

% holdup =

x 100