Experimental procedure
UNK.1
IDENTIFICATION OF ORGANIC UNKNOWNS
SECTIONS :
Physical examination
Physical properties
Solubility classification
Interpretation of Spectra
Classification and Chemical tests
Identification of Organic Unknowns
Part 1 : Classification of Unknowns I-V
Part 2 : Individual Unknowns
Always treat all chemical unknowns with caution.
Wear gloves and use in a fumehood whenever possible.
Be aware that many materials are flammable so be aware of nearby flames.
Sample vials should not be left open.
Contaminated glassware including pipettes should not be left on the bench, c
All unknowns assigned are pure compounds, and no purification should be necessary.
PHYSICAL EXAMINATION a) State Organic compounds can be solids, liquids or gases at room temperature. Knowing this information can be used to narrow the search. Solids can be powders or crystals, and the shapes of crystals can be indicative
b) Colour Common coloured compounds include nitro and nitroso compounds (yellow),
-diketones
(yellow), quinones (yellow to red), azo compounds (yellow to red), and polyconjugated olefins and ketones (yellow to red). Phenols and amines are often brown to dark-purple because of traces of air oxidation products. c) Odour Some liquid and solid amines are recognisable by their fishlike odours; esters are often pleasantly fragrant : often described as "fruity". Alcohols, ketones, aromatic hydrocarbons, and aliphatic olefins, have characteristic odours. On the unpleasant side, thiols, isonitriles, and low MW carboxylic acids are not "nice"!
PHYSICAL PROPERTIES a) Melting Point - This is a characteristic physical property of your unknown and should be determined very carefully (see melting point determination ) and this value compared with a value previously recorded in the literature (see tables of melting points). In comparing your value with melting points in the tables, a
UNK.2 leeway of several degrees should be allowed for possible errors in your determination or in the value recorded in the table. b) Boiling Point - The boiling point of a liquid depends on the molecular weight and the functional groups present. So once the functional groups are known it is possible to estimate the likely molecular weight range of the compound. For a relatively large amount of sample the boiling point of the unknown is determined by carrying out a simple distillation of the liquid. If only small amounts of liquid material are available for boiling point determination, the microboiling point apparatus should be used. If the boiling point of your unknown is higher than 230
you will be given the approximate uncorrected ( i.e.
5
) boiling point by your instructor.
Remember to make an approximate correction for Calgary atmospheric pressure before comparing your experimental value with the literature value (see boiling point determination ). If you are given a boiling point for a compound with b.pts. >230
this will correspond to the value you would measure in Calgary and the approximate correction will have to be applied.
SOLUBILITY CLASSIFICATION
The solubility of an organic compound in water or aqueous acid or base can provide evidence for the presence of several important functional groups, as indicated in the following chart:
Solvent
Water
5% NaHCO3
Some Solubility or Complete Miscibility alcohols, amines, acids, esters, ketones, aldehydes
(with 4 carbons or fewer) carboxylic acids
5% NaOH
5% HCl carboxylic acids and phenols amines
Solubility in water denotes a rather high ratio of polar groups to carbon chain length, i.e.
, a low molecular weight compound containing an -OH, -NH2 or -CO2H group, or a larger molecule containing more than one such group. The presence of an acidic -CO2H or basic -NH2 group in a water-soluble compound can be detected by a low or high pH, respectively, of the solution.
Compounds which are insoluble in water generally dissolve to a significant extent in aqueous acid or base if they form an ionic species (review Chem 351 solubility experiment ). The solubility of carboxylic acids
(KA = 10-3 to 10-5) and phenols (KA = 10-9 to 10-10) in aqueous hydroxide is due to the formation of the carboxylate or phenoxide, since they are much stronger acids than water (KA = 10-14), and the acid-base equilibria lie far to the right.
RCO2H + OH
ArOH + OH
RCO2
ArO
+ H2O
+ H2O
Carboxylic acids, but not phenols, are also stronger than carbonic acid (KA = 10-7), and are therefore also soluble in NaHCO3 solution:
RCO2H + HCO3
RCO2
+ H2O + CO2
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The solubility of amines in dilute aqueous acid similarly reflects the fact that they are stronger bases than water, and are converted to an ammonium ion:
RNH2 + H3O+ RNH3+ + H2O
Amines are the only common class of organic compounds which are protonated in dilute aqueous acid.
EXPERIMENTAL PROCEDURE
Note Due to the nature of the solubility tests , you don't need to apply all the tests to each compound, the results from one test dictate what to do next.
Place two drops of a liquid unknown, or an equivalent amount of a solid, in a test tube and add about
0.5 mL of water. If the compound dissolves completely or partially (a swirling appearance in the water, due to change in the refractive index, is an indication of some solubility), consider it soluble and proceed no further since no information will be gained by further solubility tests.
If the compound is soluble in water, test the pH of the solution with universal indicator paper. An organic acid that is soluble in water will give a solution of pH 2 to 3 (indicator paper red). An amine that is water soluble will give a pH of 10 to 11 (indicator paper blue). A blank test should be carried out with pH paper on distilled water alone as a control for this test.
If the sample is not soluble in water, repeat the test using 0.5 mL of 5% hydrochloric acid. If the compound dissolves or is significantly more soluble in acid than in water, it can be concluded that it is an amine.
If the compound is insoluble in water and in dilute acid, test for acidic properties by repeating the solubility test with 0.5 mL of 5% NaHCO3 solution. If solubility is not observed, test with 5% NaOH to check for a phenol.
INTERPRETATION OF SPECTRA Spectroscopic tables Chem 351 spectroscopy experiment
Interpret the spectra as fully as possible. Remember infra-red spectroscopy is most useful for indicating the presence of functional groups due to the vibrations of these polar covalent bonds. H-NMR spectroscopy provides important information on the hydrocarbon portions of the molecules. Remember H-
NMR can provide four levels of information : number of types of H (based on the number of peak sets), how many of each type (from the integration), what chemical types (based on the chemical shifts), and last, but not by no means least, how these are connected (from the coupling patterns). The spectral information should give indications of functional groups present and will assist greatly when applying the characteristic functional group tests.
UNK.4
CLASSIFICATION AND CHEMICAL TESTS
Note Due to the nature of the functional group tests , you don't need to and should not apply all the tests to each compound, the results from one test dictate what to do next. Such an approach can result in misleading false positives.
At this point, since the scope of the experiment is restricted, it should be possible to place the unknown in one of the six classes of compounds listed in the tables by reference to the solubility data (and infra-red spectrum if provided). A few chemical tests that give a clearly visible indication of a reaction are sometimes useful to confirm the presence of functional groups that are indicated by spectra. The reagents for this purpose are described below. These tests should be applied only as indicated, and not routinely to all unknowns; spurious and confusing results will be obtained, for example, if any of these reagents is applied to an amine.
UNK.5
ALDEHYDES AND KETONES : 2,4-DINITROPHENYLHYDRAZONES
All aldehydes and ketones readily form bright yellow to dark red 2,4-dinitrophenylhydrazones. The reagent is a solution of 2,4-dinitrophenylhydrazine and sulfuric acid in ethanol, and may be useful in the case of neutral compounds that contain a carbonyl group to distinguish between aldehydes or ketones on one hand and other carbonyl containing molecules ( e.g
. esters, amides, carboxylic acids etc.) on the other. Yellow derivatives are formed from isolated carbonyl groups and orange-red to red derivatives from aldehydes or ketones conjugated with double bonds or aromatic rings.
O
RCR'(H) +
NO
2
2,4-DNP
NHNH
NO
2
2
R
NHN
NO
2
NO
2
2,4-Dinitrophenylhydrazone
R'(H)
The pictures show a sample of a ketone before (left) and after (right) testing with 2,4-DNPH.
EXPERIMENTAL PROCEDURE
2,4-dinitrophenylhydrazine is an irritant and stains the skin and clothing. The reagent also contains sulfuric acid which is corrosive. moisture sensitive.
Avoid contact with skin, eyes and clothing.
Dissolve about 0.2 mL or 0.2 g of the unknown in 1 mL of ethanol in a test tube, and add 2 mL of the dinitrophenylhydrazine reagent. If a hydrazone crystallises, collect it on a suction filter, wash with 1 mL of ethanol and allow the crystals to dry.
In the case of your individual unknowns, this precipitate may be retained and recrystallised as a derivative though it maybe necessary to repeat on a slightly larger scale.
UNK.6
ALDEHYDES : SCHIFF'S TEST
Fuschin (a pink triphenylmethane dye) reacts with sulfurous acid to give the colourless Schiff's reagent.
Aldehydes react with Schiff's reagent to give a violetpurple colour dye to the quinoid system in the dye.
Care is needed in the interpretation of the test as some ketones and unsaturated compounds cause the paler pink colour of fuschin to reappear.
The Schiff's reagent has been prepared by taking
100 mL of a 0.1 percent aqueous solution of prosaniline hydrochloride (fuchsin) and adding 4 mL of a saturated aqueous solution of sodium bisulfite.
After 1 hr, 2 mL of concentrated hydrochloric acid is added.
A positive Schiff test on a sample of an aldehyde.
EXPERIMENTAL PROCEDURE
Add 3 drops of the unknown to 2 mL of Schiff's reagent. A magenta colour will appear within ten minutes with aldehydes. Compare the colour of your unknown with that of a known aldehyde.
Test samples in test tubes.
The two samples on the left are aldehydes, the one on the right is a control, it is a ketone not an aldehyde.
Test samples with Schiff's reagent added.
The two samples on the left show a positive result for the phenol, the one on the right is negative.
ALDEHYDES : TOLLEN'S TEST
This is also known as the silver mirror test since with very clean equipment and good technique, a distinct layer of metallic silver is deposited on the inside surface of the test tube (otherwise a grey or black precipitate may form), this can be seen in the picture to the right. The test is based on the redox reaction where the aldehyde is being oxidised and the silver
(I) reduced to metallic silver (0).
UNK.7
A positive Tollen's test on an aldehyde sample.
EXPERIMENTAL PROCEDURE
Silver nitrate is corrosive and toxic.
In a small test tube place 1.0 mL of a 5% aqueous solution of AgNO
3
followed by 1 drop of aqueous
10% NaOH solution. Add concentrated aqueous ammonia drop by drop (2-4 drops) with shaking until the precipitate of silver oxide just dissolves. Add 1 drop of the unknown (~10 mg if a solid), with shaking, and allow the reaction mixture to stand for 10 min at rt. If no reaction occurs, place the test tube in a sand bath at
40 o
C for 5 minutes. Observe the result.
METHYL KETONES (CH
3
C=O): IODOFORM TEST
Methyl ketones (RCOCH3 or ArCOCH3) react rapidly with iodine under basic conditions and are converted to the tri-iodo ketone. This product is then immediately attacked by base and the
CI3 group is displaced to give iodoform, which crystallises as a pale yellow solid with a characteristic odour. Since hydroxyl groups are oxidised to carbonyl under these conditions, compounds containing the
CHOHCH3 group also give a positive iodoform test.
RCHOHCH
3
I
2
KI
RCOCH
3
3
KI
I
2 [RCOCI
3
]
OH
_
RCO
2
-
+ CHI
3
Iodoform
This test can thus provide confirmatory evidence, if needed, for the presence of
O
C CH
3
or
OH
CH CH
3 groups in neutral compounds. As in any test of this kind, it is essential to run a known compound along with the unknown to obtain a reliable and meaningful result. You could use acetone, for example.
UNK.8
The pictures show a sample of a methyl ketone before (left) and after (right) testing with the iodoform test reagent.
EXPERIMENTAL PROCEDURE
The reagent contains iodine in potassium iodide solution at a concentration such that 2 mL of solution, on reaction with excess methyl ketone, will yield 174 mg of iodoform.
Rinse your test tube with distilled water before use. DO NOT RINSE WITH ACETONE as this will result in a false positive test (since acetone is itself a methyl ketone!).
Dissolve either 4 drops of a liquid unknown or an estimated 50 mg of a solid unknown into 1 mL of the iodine solution in a 20 x 150 mm test tube. Add 10% aqueous NaOH solution dropwise while swirling the test tube until the dark brown iodine colour disappears or until two distinct layers form. A positive test is characterised by the loss of the brown colour of the test reagent and the formation of a lemon yellow precipitate (the iodoform). If a precipitate does not form, then this is a negative test result.
If the substance to be tested is insoluble in water, then, working in the fume hood dissolve the sample in dioxane.
Iodoform can be recognised by its odour and yellow colour and, most securely, from the melting point
(119
). The substance can be isolated by suction filtration of the test suspension or by adding 2 mL of dichloromethane, shaking the stoppered test tube to extract the iodoform into the small lower layer, withdrawing the clear part of this layer with a capillary dropping tube, and evaporating it in a small tube on the steam bath. The crude solid is crystallised from methanol-water if required.
UNK.9
Iodoform test solution in test tubes.
Test samples in the iodoform test solution in test tubes.
The two samples on the left are methyl ketones, the one on the right is a control, it is a ketone but it is not a methyl ketone.
Test samples in the iodoform test solution after the addition of NaOH solution.
The two samples on the left are positive tests for methyl ketones, the one on the right is a negative result (control).
UNK.10 b) PHENOLS: FERRIC CHLORIDE TEST
Most phenols (and stable enols) give a red or violet complex with ferric chloride solution (for the specific colours produced see Openshaw p.43).
If solubility and/or infra-red data suggest a phenol, this test can be applied for confirmation if desired. The test should be run first with authentic phenol so that you know the appearance of a positive test.
The pictures show a sample of a phenol before (left) and after (right) testing with the ferric chloride test reagent.
EXPERIMENTAL PROCEDURE
Place one drop or crystal of the unknown in a test tube and add 1 mL of dichloromethane. Add one drop of triethylamine and swirl gently to dissolve and mix. Add 3 drops of the FeCl
3
solution. A positive test is characterised by the formation of a bright red, orange or violet complex, while a negative test is characterised by a pale yellow colour.
H.T. Openshaw, A Laboratory Manual of Qualitative Organic Analysis, 1965.
UNK.11
Test samples in test tubes.
The two samples on the left are phenols, the one on the right is a control, it is not a phenol.
Test samples dissolved in CH
2
Cl
2
and with 1 drop of triethylamine added.
Test samples dissolved in CH
2
Cl
2
, 1 drop of triethylamine and ferric chloride solution added.
The two samples on the left show a positive result for the phenol, the one on the right is negative.
UNK.12
IDENTIFICATION OF ORGANIC UNKNOWNS
Always treat all chemical unknowns with caution.
Wear gloves and use in a fumehood whenever possible.
Be aware that many materials are flammable so be aware of nearby flames.
Sample vials should not be left open.
Contaminated glassware including pipettes should not be left on the bench.
EXPERIMENTAL PROCEDURE
There are two parts to the experiment. In Part I you will be provided with samples of five unknowns, and their infra-red and n.m.r. spectra (provided below). You need to carry out a preliminary classification of these using the spectra provided, and the solubility tests and chemical tests described here.
In Part II you will be issued with two unknown compounds. For one unknown you will also be given the corresponding infra-red and N.M.R. spectra. You will be asked to classify and, by means of the preparation of crystalline derivatives, to identify your unknown compound.
Part I . PRELIMINARY CLASSIFICATION EXPERIMENT
The unknown compounds for this part of the experiment are labeled A - E and their n.m.r. and infra-red spectra are shown on the following pages. First classify each compound according to one of these general groups using the functional group tests. You should be able to classify each compound as one of the following:
1. aldehyde or ketone 2. alcohol 3. phenol 4. carboxylic acid 5. amine 6. ester
These functional group results along with the spectral data, you should be able to identify the compound
( i.e.
draw its structure). You are not required to measure the melting points or boiling points of these samples.
1. Solubilities
Obtain samples of the five compounds in labeled test tubes and go through the solubility tests on each as described; record the data on the report sheet.
2. Infra-red Spectra
Examine the infra-red spectra of the compounds; note peaks in the 4000 to 1600 cm-1 region due to functional. Note any confirmatory data from the NMR spectra (blackened peaks due to exchangeable protons: -OH or -NH).
UNK.13
3. Chemical Tests
Carry out any functional group tests that seem to be required in view of the solubility and spectral data and record the results. Credit will be given for a rationale approach to this part of the experiment.
4. Classification
From the combined data classify each of the compounds as (1) aldehyde or ketone, (2) alcohol, (3) phenol, (4) acid, (5) amine or (6) ester. Summarise the observations and conclusions that led you to your assignments.
5. N.M.R. Data
Examine the n.m.r. spectra; see if you can deduce the structures of any of the compounds. In looking at the spectra, observe the following points and record them in a systematic way: a. List each distinct peak or multiplet and the relative number of protons from the integration line.
To arrive at the relative areas of the peaks, measure the heights in cm of each major step in the integration curve and derive the smallest set of integers that are in the same ratio. If there is a clearly recognisable CH3 peak, set the value of this at 3 and derive the closest whole number values for the other peaks.
To illustrate, the spectrum of compound A, for example, contains one group in the 6.5 to 7.0 p.p.m. region and a singlet at 3.3 p.p.m. The relative heights, adjusted to the closest whole number ratio, are 5:2. b. Note the position or chemical shift of the peaks or groups, and from the table, assign the type of proton ( i.e.
aromatic, vinyl, alkyl, CHO, CO
2
H and so forth). c. Record characteristic splitting or appearance of peaks, such as multiplet, doublet and so on, and their significance. For example, a singlet with 3 protons in the region 2 to 3 p.p.m. indicates a CH3 group on a carbon atom with no protons attached.
REPORT
PART I : GENERAL UNKNOWNS I - V
The report for Part I should be submitted at the start of the second laboratory period for this experiment.
This report is to be completed on the report template provided.
UNK.14
Unknown I mpt. 43 o
C
Unknown II bpt. 56 o
C / 760 mmHg
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UNK.16
Unknown III bpt. 184 o
C / 760 mmHg
Unknown IV bpt. 227 o
C / 760 mmHg
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UNK.18
Unknown V mpt. 122 o
C
UNK.19
Part II INDIVIDUAL UNKNOWNS
After you have completed the preliminary work on the general unknowns A-E, you will be given two unknown samples to identify, one with spectra and one without. You are required to identify these unknowns according to the methodology outlined and the procedures provided.
Always treat all chemical unknowns with caution.
Wear gloves and use in a fumehood whenever possible.
Be aware that many materials are flammable so be aware of nearby flames.
Sample vials should not be left open.
Contaminated glassware including pipettes should not be left on the bench.
EXPERIMENTAL PROCEDURE
1. Determine the melting point, if a solid, or the boiling point, if a liquid, unless instructed to omit boiling point.
2. Carry out solubility tests and spectral examination, and classify the compound based in type of functional group.
3. At this stage, review all the data, draw all conclusions possible and then examine the appropriate table of compounds . Write out the structures of the compounds in the list that appear to be possibilities.
Choose a derivative that will distinguish among these.
4. Prepare and recrystallise a derivative and measure its melting point and compare with the data given in the table in order to confirm the identification. Submit your derivatives to your instructor with your report, ensuring that your derivative is correctly and completely labeled. The quality of the derivative will be assessed by the TAs.
Derivatives
A derivative is a reaction product that is characteristic for the unknown, and provides the final evidence in the identification. The melting point of the derivative is an additional physical constant for comparison, and the fact that the unknown reacts with a given reagent in the predicted way is itself confirmatory evidence for the functional group.
The derivatives listed in the tables are known, with a few exceptions, for all of the compounds included in each table, and they can be obtained from any of the compounds by simple, standard methods. The derivative should be chosen to distinguish among possible candidates based on differences in melting points or boiling points. In a few cases, preparation of two derivatives may be desirable to eliminate any uncertainty.
When possible, select a derivative that has a melting point between 100 and 200
. General procedures are given below for each type of derivative, but the final crystallisation details will vary somewhat, depending on the solubility of the specific derivative. Recall the generalisation that the higher the melting point, the lower the solubility. Most of the derivatives will need to be recrystallised to give accurate melting points. Where
UNK.20 possible, suitable recrystallisation solvents are suggested, but there may need to be some trial and error, so make sure you make enough derivative and test the recrystallisation on small portions.
In general, most of these derivatisation procedures should be performed with clean , dry glassware.
DERIVATIVE PROCEDURES
Wear gloves at all times.
Work in a fumehood whenever possible.
Procedures for the preparation of derivatives indicated for the following functional groups can be found on the following pages:
Functional group carboxylic acids alcohols and phenols aldehydes and ketones
Derivative amide or anilide dinitrobenzoates or urethanes
Page
17
19
20 amines esters dinitrophenylhydrazones, semicarbazones or oximes acetamides or benzamides via saponification
21
22
GENERAL HAZARDS (Common reagents and solvents)
Acetone is extremely flammable and volatile. It is an eye and skin irritant.
Avoid contact with skin, eyes and clothing.
Dichloromethane is toxic, an irritant and absorbed through the skin. It is harmful if inhaled.
Diethyl ether is extremely volatile and flammable. Ensure there are no flames or hot electrical equipment in the vicinity.
Dimethylformamide is harmful and absorbed through the skin. Avoid contact.
Ethanol is flammable.
Ethyl acetate is very volatile and flammable.
Hexane / petroleum ether is extremely flammable.
Methanol is volatile, flammable and toxic.
Hydrochloric acid is a skin irritant.
Sulfuric acid is corrosive and causes severe burns.
Sodium hydroxide solutions are corrosive and can cause burns.
UNK.21 a) Acids
The most satisfactory general derivatives of acids are the amides or anilides (N-phenyl amides). These are prepared in a two-step procedure by first converting the acid to the acid chloride, and then treating the acid chloride with either ammonia or aniline.
RCO
2
H
RCOCl
RCOCl
+
+
+
SOCl
2
Thionyl chloride
2 NH
2 C
6
H
3
5
NH
2
RCOCl
Acid chloride
+ SO
2
+ ClH
RCONH
2
Amide
+ NH
4
Cl
RCONHC
6
H
5
Anilide
+ C
6
H
+
5
NH
3
Cl
_
Acid Chloride .
Thionyl chloride causes burns and is moisture sensitive creating HCl and SO
2
.
Avoid contact with the skin. Use in a fumehood whenever possible.
Acid (or acyl) chlorides are highly reactive. Ensure that the solution is cold and ONLY add the acid chloride DROPWISE using a pipette. Use in a fumehood whenever possible.
The first procedure (1) is suitable for most acids, and is the more convenient one. A few compounds such as phenylacetic acid, with a reactive
CH2
group, require the milder conditions of procedure (2), if you think you need to use the second procedure, or procedure 1 fails, check with your instructor. Your apparatus must be dry for these procedures.
1. In a 18 x 150 mm test tube, carefully mix 3 mL of thionyl chloride with 1g of the acid and add 5 drops of dimethylformamide. Set up a Bunsen burner in the hood, with a tripod and wire gauze. Adjust the Bunsen burner to give a small, blue flame. Hold the tube in a clamp and gently heat the mixture to boiling / reflux over the heated wire gauze (Caution: Do not heat too vigourously or the reaction mixture will become black).
Continue heating for at least 10 minutes at a rate such that most of the liquid condenses ( i.e.
refluxing) on the wall of the tube. The acid dissolves as it reacts; with high-melting insoluble acids it may be necessary to add a little more thionyl chloride and heat for longer. When all of the acid dissolves, heat a little more strongly to distill off the excess thionyl chloride (bpt. 79
C). After the solution has been concentrated to an oil, tip the tube sideways to permit the heavy vapours to escape. Ensure that you heat the tube away from the mouth so that vapours are not ignited. Carefully cool the acid chloride to room temperature using an ice bath before using in the next step.
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2. For sensitive acids, carefully mix 1 g of acid and 2 mL of thionyl chloride and 5 drops of dimethylformamide in a test tube in the hood as in procedure (1), and fit a drying tube by means of a small one-hole rubber stopper to the mouth of the test tube. Set the tube in a beaker in the hood and shake occasionally and warm in your hands for an hour. If HCl evolution and condensation cause the drying tube to become moist, clean out and dry the tube and replace with fresh cotton and Drierite. Proceed with care !
Amide .
Acid (or acyl) chlorides can react violently with ammonia. Ensure that the solution is cold and ONLY add the acid chloride DROPWISE using a pipette.
Use in a fumehood whenever possible.
Ammonia is an irritant to skin and eyes and is harmful if inhaled.
To prepare the amide, place 10 mL of concentrated aqueous ammonia and an equal volume of ice in a 50 mL beaker. In the hood, very carefully add the acid chloride drop wise using a transfer pipette and bulb, to the cold ammonia. After the vigorous reaction occurs, collect the precipitated amide on a suction filter, wash with a little water and allow it to air dry. Recrystallisation is usually not necessary; if the melting point does not agree with that expected for the derivative in question, recrystallisation can be carried out from a small volume of ethanol or aq. ethanol (i.e. ethanol plus a few drops of water) or methanol.
Anilide .
Aniline is toxic and can be absorbed through the skin. Use in a fumehood whenever possible.
Acid (or acyl) chlorides can react violently with amines. Ensure that the solution is cold and ONLY add the acid chloride DROPWISE using a pipette.
Use in a fumehood whenever possible.
Carefully dilute the acid chloride with 5 mL of dichloromethane and add it to a solution of 2 mL of aniline in 10 mL of dichloromethane. After mixing, allow the reaction to stand for a few minutes, add 10 mL of water and transfer the mixture to a separatory funnel in order to carry out the following extraction procedure. Add more solvent if necessary to dissolve all the solid. At this point, it is convenient to add sufficient diethyl ether (25 to
30 mL) to make the organic layer lighter than water. (Be sure no flames are near before pouring ether!)
Wash the organic phase by shaking with 10 mL of 1 N HCl, drain off the aqueous layer and, using test paper, check that it is acidic. If it is not, repeat the HCl wash and check again. After removing the aqueous acid layer, wash the dichloromethane solution with 5 mL of 0.5 N NaOH, drain off the alkaline layer and then wash with water. Transfer the organic layer to an Erlenmeyer flask and add a teaspoonful of anhydrous MgSO4.
Shake and allow to stand for a few minutes, and then filter through a filter paper into a clean, dry Erlenmeyer
UNK.23 flask. Add a boiling stone and evaporate the solvent on the steam bath. If the anilide does not crystallise spontaneously during the evaporation, concentrate to about 5 mL volume, add 10 mL of ether and cool.
Collect the product by suction filtration and determine the melting point. Recrystallisation can be carried out from a small volume of ethanol or aq. ethanol (i.e. ethanol plus a few drops of water) or aq. methanol. b) Alcohols and Phenols
These compounds can be converted to crystalline 3,5-dinitrobenzoate esters by reaction with the acid chloride and pyridine. For a few phenols, only the benzoate ester is recorded; in this case, substitute benzoyl chloride in the procedure. Another derivative is an ester of a special type known as a urethane or carbamate, which is formed by treatment with an isocyanate.
O O
ROH +
O
2
N CCl pyridine
O
2
N COR
+ HCl
NO
2
NCO
NO
2
3,5-Dinitrobenzoate ester
O
NHCOR
ROH +
Phenyl
isocyanate
Phenyl urethane
Isocyanates are exceptionally reactive compounds, and in any manipulations with isocyanates, the following reactions leading to the diarylurea will occur if water is present:
O
ArN C O + H
2
O (ArNHCOH) ArNH
2
+ CO
2
ArN C O + ArNH
2
ArNHCONHAr
Diarylurea
The diaryl ureas are very high-melting insoluble compounds (diphenylurea mpt = 241 o
C, dinaphthylurea, mp =
297
C) and can interfere with the isolation of the desired derivative. Therefore, all the glassware must be dry, and an excess of the isocyanate should be avoided. In the first instance, you should try to prepare the phenylurethane. If this does not produce crystals, or the mpt of the phenylurethane is predicted to be too low, then prepare the
-naphthylurethane.
UNK.24
3,5-Dinitrobenzoates .
3,5-dinitrobenzoyl chloride is a strong irritant and moisture sensitive. Use in a fumehood whenever possible. Avoid contact with skin, eyes and clothing.
Recap the bottle immediately after use.
Pyridine is toxic and has an unpleasant odour. Use in a fumehood whenever possible
Dissolve 0.5 g of the alcohol or phenol in 2 mL of pyridine and add 0.5 g of 3,5-dinitrobenzoyl chloride. Heat the solution gently for 10 minutes and then pour it into 10 mL of water. If a solid ester precipitates, collect this on a filter, wash with water and allow it to dry. Frequently the product separates as an oil. In this case, extract the mixture with ether, wash the ether solution with 1 N HCl as described above for anilides and follow that procedure. The esters generally have rather high solubility in diethyl ether; petroleum ether (hexane) is usually a satisfactory solvent for recrystallisation or ethanol or aq. ethanol (i.e. ethanol plus a few drops of water) or methanol. Caution: The mpt. of 3,5-dinitrobenzoic acid is 204-5 o
C.
Phenylurethanes and
-Naphthylurethanes .
Isocyanates are lachrymators (causes tears) and are moisture sensitive. Use in a fumehood whenever possible. Recap the bottle immediately after use.
Phenyl isocyanate is toxic and corrosive. Use in a fumehood whenever possible.
Hexane is extremely flammable.
Place 1 g or 1 mL of the unknown in a dry test tube* and add 0.5 mL of phenylisocyanate (or
-naphthylisocyanate). If the unknown is a phenol, 2 drops of pyridine should also be added as a catalyst. If there is no immediate reaction, then warm the mixture gently over a heated wire gauze for about 5 min. (the reaction mixture should darken, but avoid overheating). Cool the mixture in an ice bath and scratch the sides of the test tube to induce crystallisation if required. If the urethane is slow to crystallise, add 2 mL of petroleum ether. If an insoluble, fine white powder is present, this is the diarylurea (see above) and it must be removed by filtering the warm solution. Then cool on ice or concentrate the filtrate to crystallise the derivative. The urethanes can be recrystallised from petroleum ether or hexanes if necessary.
(* heat the test tube in a Bunsen flame to remove any moisture before use) c) Aldehydes and Ketones
Semicarbazones and dinitrophenylhydrazones are the most common derivatives, and the choice usually depends on the melting point.
UNK.25
O O H O
RCH + NH
2
NHCNH
2
Semicarbazide
R C N NHCNH
2
Semicarbazone
The 2,4-dinitrophenylhydrazone is generally best for aliphatic compounds. For aromatic aldehydes and ketones, the melting point of the 2,4-dinitrophenylhydrazone and sometimes the semicarbazone may be too high for convenience and is actually a decomposition temperature. In this case, the oxime is another possibility. A drawback of oximes is that two stereoisomeric forms with different melting points can be obtained. Melting points of both forms are given in the table; either may be observed.
2,4-Dinitrophenylhydrazones.
2,4-dinitrophenylhydrazine is an irritant and stains the skin and clothing. The reagent also contains sulfuric acid which is corrosive. Avoid contact with skin, eyes and clothing.
The preparation of these derivatives is carried out as outlined in the classification test described above
(except you may need to scale it up). Collect the hydrazone by filtration, wash with ethanol and dry. For best results recrystallise (hot ethanol is a good solvent to try first, ethyl acetate or aq. ethanol can be used if needed).
O H
RCH + NH
2
NH NO
2
R C N N
H
NO
2
+ H
2
O
O
2
N
2,4-dinitrophenylhydrazine
O
2
N
2,4-dinitrophenylhydrazone
Semicarbazones.
Semicarbazide hydrochloride is toxic.
Mix 0.5 g of semicarbazide hydrochloride and 1 g of sodium acetate in 2 to 3 mL of water, grinding with a stirring rod. When the large crystals have dissolved, add an equal volume of methanol and then 0.5 g of the aldehyde or ketone. Warm the mixture to boiling on a steam bath and then allow it to cool. Add a few drops of water and, if necessary, cool and scratch to crystallise the semicarbazone. Recrystallisation can be carried out from a small volume of water or 25% to 50% aq. ethanol or aq. methanol
O
RCH +
O
NH
2
NHCNH
2
Semicarbazide
R
H
C N
O
NHCNH
Semicarbazone
2
+ H
2
O
UNK.26
Oximes
Hydroxylamine hydrochloride is corrosive and toxic. Avoid contact with skin, eyes and clothing.
Follow the procedure for semicarbazones, using hydroxylamine hydrochloride instead of semicarbazide HCl.
OH
O N
RCH + NH
2
OH
Hydroxylamine
R C H
Oxime
+ H
2
O d) Amines
The N-substituted acetamides or benzamides are easily prepared; the choice will usually depend on which derivative provides the best differentiation between two possible compounds.
RNH
2
+ (CH
3
CO)
2
O
Acetic anhydride
RNHCOCH
3
Acetamide
+ CH
3
CO
2
H
RNH
2
+ C
6
H
5
COCl
Benzoyl chloride
RNHCOC
6
H
5
Benzamide
+ HCl
Acetamides .
Acetic anhydride is toxic, corrosive and a lachrymator (causes tears) and a skin irritant. Use in a fumehood whenever possible. Avoid contact with skin, eyes and clothing.
Dissolve 0.5 g of the amine in 1 mL of acetic anhydride and heat for a few minutes on the steam bath.
Add 1 to 2 mL of water and stir until no oily droplets of acetic anhydride are present. Crystals of the amide usually form on cooling the solution. Collect the crystals on a suction filter, wash with a few milliliters of a 1:1 mixture of alcohol and water and allow to dry. If crystallisation does not occur, add ether, transfer to a separatory funnel and proceed as described for the preparation of anilides from acids. Recrystallisation can be carried out from ethanol or aq. ethanol (i.e. ethanol plus a few drops of water) or methanol.
Benzamides .
Benzoyl chloride is a lachrymator (causes tears) and a skin irritant. Use in a fumehood whenever possible.
Pyridine is toxic and has an unpleasant odour. Use in a fumehood whenever possible.
UNK.27
Mix 0.5 g of the amine and 1 mL of pyridine in a test tube, and cool the solution in an ice bath. Add 0.5 mL of benzoyl chloride, stir the mixture and allow it to come to room temperature. Add 1 mL of water and then 1 N hydrochloric acid in small portions until the mixture is acidic to test paper. Stir the solid with a glass rod, grinding up any lumps. Collect the solid on a suction filter and wash first with water and then 1:1 alcohol-water. Allow the solid to dry. Recrystallisation can be carried out from ethanol or aq. ethanol (i.e. ethanol plus a few drops of water) or methanol. e) Esters
For the esters that are used as unknowns in this experiment, the most suitable derivative is the acid obtained by saponification, although the acid does not provide information about the alcohol part of the ester.
Since it is not practical in this experiment to isolate the alcohol and prepare a derivative of it, the alkyl group in the ester must be identified from the n.m.r. spectrum.
O
O
RCOR' + NaOH RCONa
Sodium salt
+ R'OH
O
RCONa + HCl RCO
2
H
Saponification Procedure .
Mix 1 g of the ester and 10 mL of 2 N NaOH solution in a 50 mL round-bottom flask. Set-up the flask on a ring and wire gauze and connect a condenser (vertically) for refluxing. Add a boiling stone, start the condenser water, heat the mixture to boiling for 15 to 20 minutes and then cool the flask. If a significant amount of ester (oily droplets) is still present at this point, add 5 to 6 pellets of NaOH or KOH and a fresh boiling stone and heat the mixture under reflux for another 10 minutes.
With some esters it may be necessary to add 10 mL of ethanol as a solvent. When ethanol is used, it should be removed by distillation before isolating the acid. After refluxing for 20 minutes with aqueous alcoholic hydroxide, allow the solution to cool somewhat and arrange the condenser, with a distillation head and adapter, for distillation. Distill until the volume of distillate is equal to the volume of alcohol added.
Transfer the aqueous solution of the acid salt to a 50 mL Erlenmeyer flask, cool in an ice bath and add, drop by drop, concentrated hydrochloric acid. Stir or swirl the mixture as the hydrochloric acid is added and continue until the solution is acidic to test paper. Collect the acid product on a suction filter, wash with water and allow to dry. Recrystallisation can be carried out from water or aq. ethanol (i.e. ethanol plus a few drops of water).
UNK.28
CLEAN UP
The vials of unknowns should be placed in the special lined box provided.
Aqueous solutions should be poured into the container for aqueous waste.
Organic wastes should be poured into the blue drum for organic waste in the fumehood.
Used pipettes should be rinsed with acetone then put into the special container provided
REPORT
PART II : INDIVIDUAL UNKNOWNS
The report for Part II should have a similar format to that used for Part I.
Write separate reports for each of the two unknowns.
No need to write up the procedures, but make sure you describe any deviations in procedures ( e.g.
functional group tests or preparations of derivatives etc.
) or “strange results”.
Tabulate your results (e.g. table of tests, melting points etc. table of spectroscopic data.
For the unknown with spectra, you should include the spectra .
The reports should be written to show your deductive reasoning and not as an "after the fact" analysis.
There is no need to show mechanisms of the reactions involved in the preparations of derivatives or functional group tests, but equations would be a good idea.
You must hand in labeled samples of your derivatives . .
1. Title, Date, Identity # of Unknown (include a drawing of the structures)
2. Objectives of the Experiment
3. Results (tabulate your results,for the unknown with spectra, make sure you include the actual spectra)
4. Discussion (give a concise rationale of the thought processes that show why you did what you did and how that led to the final answer).
5. Conclusions
6. References
