R. M. Southam The Polytechnic Huddersfield. HD1 3DH England
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a.
Organic qualitative analysis is included in most undergraduate chemistry courses for a number of reasons: it serves as a means of teaching functional group behavior; it assists in the development of certain skills in reasoning; and it equips the student with an expertise which he may well need later as a professional chemist. While the analysis of a given series of single and binary unknowns may achieve all of these objectives, we have found that it adds interest and meaning if the student can see that his analysis is serving some immediate purpose. To this end, we have sought to develop some student investigations in which the unknowns for analysis are obtained in a rational manner hv the students themselves. the analvsis forming an essential part of the investigation. We have found the experiments detailed below suitable: they give rise to a fair cross-section of functional group types, and the compounds and chemistry involved are all suitable for elementary classes. The way in which these experiments might be used by the instructor will clearly depend on the hackmound of the students, the objectives of i h e course, and the availability of instrumentation; the presentation given here is one of many that are possible. Experiment 1: Investigation of the Stereochemistry of an Oxime The Problem In the reaction sequence which follows, one of the two stereoisomeric oximes of p-bromoacetophenone will be prepared and its stereochemistry established. The stereochemistry of this oxime may be determined by identifying the amide to which it is converted when it undergoes the Beckmann rearrangement. This rearrangement is stereospecific under appropriate conditions, and is known to involve migration to nitrogen of the alkyl or aryl group anti to the hydroxyl
The two stereoisomeric oximes of a n unsvrnmetrical ketone such as p-bromoacetophenone are thus expected to yield different N-substituted amides on rearrangement. and a n identification of the amide formed from a particu: lar oxime leads directly to a n assignment of stereochemistry to that oxime. The amide will he identified through characterization of compound (I), one of the two products of its acid-catalyzed hydrolysis. Procedure Dissolve p-bromoacetophenone (7.5 g, 0.038 mole) in ethanol (18 ml) contained in a 50-ml round-bottomed flask. Add a solution of hydroxylamine hydrochloride (4.5 g, 0.065 male) and sodium acetate trihydrate (4.5 g, 0.033 mole) in warm water (12 ml), and heat the mixture under reflux on a water bath for 20 min. Rapidly filter the hot solution, then cool the filtrate first under running water, then in ice. Collect the crystalline product at the 34 1 Journal of Chemical Education
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stuales tor tne organic Qual Lab pump, wash with a little cold 50% ethanol, and dry at 80°C. Ree&d its melting point. Heat polyphosphoric acid (50 g) in a 100-ml Erlenmeyer flask on a hoilina water bath. Add D-bromoaceto~henane oxime (5.0 a. 0.023 malej, and stir continu&sly with a glass rod for 10 mi;, maintaining the external heating. Pour the hot solution onto crushed ice (-100 g), and triturate until the viscous mass has dissolved, leaving behind an aqueous suspension of amide. Collect the crude product at the pump, wash it with cold water until the filtrate is no longer acidic, then suek it as dry as possible. Recrystallize it from ethanol, and dry the purified product at 80'C. Record the melting paint of your amide, and hence draw a provisional conclusion as to its identity. Gently heat under reflux for 30 min a mixture of the amide (2.5 g, 0.012 mole) and concentrated hydrochloric acid (12 ml) in a 50-ml round-bottomed flask. (Work in a hood, or make provision for the absorption of HCI fumes.) Dilute the contents of the flask with an equal volume of water, then pour slowly into concd ammonia (12 ml) chilled to 0%. Cool the mixture to 0%. and scratch if need be to solidify the precipitated product, compound (I). Collect (I) at the pump, wash it with a little cold water, and suek it dry. Characterize compound (I), and hence draw a firm conclusion as to the identity of the amide from which it was derived. What, therefore, was the stereochemistry of the mime you prepared initially? Solution and Typical Results The oxime, m p 127-8°C. must possess the E configuration as the derived amide leads to p-bmmoaniline on hydrolysis.'
3.0 g (60%) mp 166-7.W (lit. ( 1 ) mp 167°C)
ill
1.4 g (70%) mp 61-2°C (lit. (11 mp WCI Experiment 2: Structure Determination Through Chemical Degradation The Problem Compound (II) is a polyfunctional compound which gave on analysis the following data: C = 60.090, H = 3.590, C1 = 13.690, N = 10.7%. The structure of compound (11) may he deduced by isolation and identification of compounds (111) and (IV) into which (11) is converted on treatment with aqueous acid. Carry out the transformation by the procedure given below, and having characterized (111) and (IV) suggest a structure for compound (11).
Procedure Place compound (11) (12.5 g) and 4 N hydrochloric acid (20 ml) in a 50-ml round-bottomed flask equipped for steam distillation. Lag the still head with glass wool, and generate the steam 'internally' by boiling vigorously the contents of the reaction flask; maintain the volume constant by addition of water from a dropping funnel. Collect the steam distillate in a 50-ml measuring cylinder, and continue the distillation until no further significant amount of compound (ID) distils (50 ml of distillate, collected over 20-30 min, is normally sufficient). Pour the hot, clear solution remaining in the distillation flask into a mixture of ice-cold 20% aqueous sodium hydroxide (20 ml) and water (5 ml). Chill to 0-5°C. Filter off the precipitate of compound (IV),and wash it with water until the filtrate is no longer alkaline to litmus paper. Suck the cake dry, and recrystallize it from a mixture of ethanol and water (10:90, v h ) . Dry your purified product (IV) at 80%. and record its melting point. Extract the steam distillate with ether (30 ml). Wash the ethereal extract with 5% aqueous sodium bicarbonate (25 ml), and dry it aver anhydrous magnesium sulfate. Filter off the drying agent, and remove the ether by distillation from a water bath. When the rate of distillation becomes negligible, dispose of the distillate, and replace the water bath by a burner and gauze. Lag the still head, and distil until the still head thermometer reaches 120°C. Turn off the burner, replace the water condenser by an air condenser, and continue the distillation, collecting compound (111) as a clear colorless liquid. Record its boiling point. Solution and Typical Results Compound (11) is a Schiff base2
4.6 g (a%) bp 207-9°C (lit. (1) bp 213°C)
4.7 g (71%) mp 111-2% (lit. ( I ) mp ll4"C)
Experiment 3: Structure Determination through Chemical Degradation The Problem Compound (V) contains no elements detectable by Lassaigne sodium fusion. A molecular weight determination gave a value of 209+5. Convert (V) t o compounds (VI) and (VII) using t h e given procedure, identify (VI) and (VII), and hence deduce the structureof compound (V). Procedure Place a mixture of compound (V) (15.9 g), 4 M potassium hydroxide (50 ml), and ethanol (25 ml) in a 250-ml round-bottomed flask equipped with a reflux condenser. Heat the mixture under vigorous reflux far 15 min with a burner and gauze. Rearrange the apparatus for distillation, lag the still head, and distil until 25-30 ml of distillate (largely ethanol) have been collected in a pre-calibrated receiver. Discard this distillate. Cool the contents of the distillation flask to room temperature, and isolate compounds (VI) and (VII) as follows. Transfer the contents of the reaction vessel to a 100-ml separatory funnel, and extract them with three 20-ml portions of ether. (Keep the aqueous layer for isolation of eompound (VI), below.) Combine the ethereal extracts, wash with brine (20 ml), then dry over anhydrous magnesium sulfate. Taking the customary precautions, remove the desiccant by filtration and the ether by distillation. When the rate of distillation becomes negligible, dispose of the distillate, lag the still head, and heat the residual oil strongly with burner and gauze. When the still head temperature reaches about 130% extinguish the flame and replace the water condenser by an air condenser. Resume distillation and collect pure eompound (VII) over a boiling point range of no more than 4°C. Record its boiling point.
Take the aqueous layer obtained in the ether extraction and pour it cautiously into concentrated hydrochloric acid (20 ml). Cool in ice, and filter off crude compound (VI) at the pump. Wash it well with ice-cold water, then recrystallize from ethanol.:water (1:4, "1"). Dry at 95°C and record the melting point. Solution a n d Typical Results
n
(VI) 7.0 g (76%) mp 120-2% llit. ( 1 ) mp 122%)
(VII) 5.0 g (62%) bp 201-5% (lit. ( I ) hp 205W
Experiment 4: Structure Determination Through Chemical Degradation The Problem Compound (VDI), m p 101-2"C, has been shown by mass spectrometric measurement t o have a molecular weight of 179. Treatment of (VIII) with acidified dichromate solution produces compound (M). A chemical a n d spectroscopic examination of (VIII), together with a n identification of (IX), enables t h e structure of (VIII) t o h e deduced. Procedure Investigation of Compound (VIII). Deduce what you can about (VIII) on the basis of a n elements test, solubility tests, spectral interpretation, and functional group tests. Conversion of Compound (VIIIl to Compound IIX). Dissolve sodium dichromate dihydrate (12.5 g, 0.042 mole) in water (45 ml) in a 500-ml Erlenmeyer flask. Add concentrated sulfuric acid (37 ml, 0.68 mole) cautiously with swirling. Heat the resultant solution on a hot plate to 110-12O0C, and a d d compound (VIII) (5.0 g, 0.028 mole) over 5 min, with swirling, so a s to maintain the internal temperature within the range 110-130°C. When addition is complete, heat a t 115-130°C for a further 10 min, with continued swirling. Remove the flask from the hot plate, and while still hot cautiously add water (75 ml). Chill in ice, filter off the precipitate a t t h e pump, and wash it with a little ice-cold water. Dissolve the cake in 2 N aqueous sodium hydroxide (20 ml), filter off any insoluble material, and acidify the filtrate t o p H 5 1 with concentrate d hydrochloric acid. Chill in ice. Collect compound (IX) a t the pump, wash it with a little ice-cold water, and recrystallize it from a water-ethanol pair (2:1, vlv). Dly your purified product a t 80°C, and record its melting point. Identify (IX) using a n appropriate combination of spectroscopic a n d chemical methods. Interpretation of Results. Write a structure for com~ o u n d(VlII) . . which is consistent with all the information ;ou now have about it. Check your deduction by conducting a literature search for (VIII) in Chemical Abstracts or We have chosen polyphosphoric acid, rather than phosphorus pntachloride-ether, to rearrange the mime on grounds of convenience and yield. As we have found the p-bromoaeetanilide is the chief product in both cases, acid-catalyzed stereomutation of the oxime cannot be of importance under our conditions. For a review of the Beckmann rearrangement see reference i?!. ZMaterial of adequate purity may be prepared by adding ochlorobenzaldehyde (140 g. 1.00 mole) and acetic acid (5 ml) to a hot solution of m-nitroaniline (138 g, 1 male) in ethanol (450 ml). The solution is allowed to cool, and the product which separates is filtered and washed with cold ethanol. Pure material, lit. (3) mp 114-16'C. may be obtained on recrystallization from ethanol. Volume 53, Number 1, January 1976 1 35
aliphatic side chain, while the latter simply involves nitration. In the study which follows you will first resolve this conflict using a 'modern' and a 'classical' method, and then go on to investigate the reaction which occurs when compound (X) is heated under reflux in aqueous ammonia.
Nmr spectrum o f compound (X); recorded at 60 MHz as a solution in acetone, with TMS as internal reference. inset: expansion of the aramatiC resonances.
Solution and Typical Results
m-Nitropropiophenone3 has the present advantage of not being listed in the commonly used texts of qualitative analysis. Experiment 5: An Investigation of the Compound Formed when Phenylacetic Acid Reacts with Fuming Nitric Acid
Procedure Identification of Compound ( X i . Study the nmr spectrum provided and decide between the two contending structures. Explain how the aromatic resonances clearly demonstrate that (X) is a 1,2,4-trisuhstituted benzene. Devise and carrv out two mixture meltine-noint - . determinations to confirm your conclusion: a sample of (XI, and authentic samples of the two nitro-acids are provided. An ~nvestigationof the Reaction uhich 0Ecurs when ( X ! is Heated in Aqueous Ammonia. (Wear disposable gloves in all operations in which (X) and (XI) are handled, as they may both be 'harmful by skin absorption,' being nitro compounds.) Dissolve compound (X) (2.0 g) in a mixture of 2 N ammonia (10 ml) and water (20 ml) contained in a 50-ml round-bottomed flask. Equip the flask with a reflua condenser, and then heat the solution under reflux with burner and gauze for 30 mi", noting all changes which occur. Cool the reaction flask, with swirling, in ice-water and scratch if necessary to induce compound (XI) to crystallize. Rinse down any (XI) which may have steam-distilled up into the condenser. Collect (XI) at the pump, wash with water, suck dry, then recrystallize from ethanol. Dry at 50°C. Identify compound (XI) on the basis of its melting point, its solubility properties, and its ir and nmr spectra. Write a n equation for the reaction you have investigated. Bearing in mind what you know about formally similar reactions, write a mechanism for the reaction and explain why neither henzoic acid nor phenylacetic acid undergo a n analogous reaction under the same conditions. Solution and Typical Results (X)is 2,4-dinitrophenylacetic acid,4 whose salts decarboxylate readily on heating (9)
The Problem When phenylacetic acid is heated under reflux with fuming nitric acid, compound (X), mp 181-YC, is formed in high yield. There are conflicting reports in the chemical literature as to what (X) is. One report (Fi! claims that (X) is 2,4-dinitrobenzoic acid, while another (6! states that (X) is 2,4-dinitrophenylacetic acid COOH
CHr-COOH
(XI) 085 g (53%) mp 70°C ( l i t ( 1 ) mp 72°C)
CH2-COOH
Nmr interpretation
(lit. ( 1 ) mp 183'C)
(lit. ( 7 ) mp 179-1RO"C)
Both claims are quite plausible, as the former involves nitration accompanied by an oxidative degradation of the m-Nitropropiophenone may he prepared from prapiaphenane using the method of reference (41, observing careful temperature control. I n our experience, nitration af phenylacetic acid according to the procedure of reference 15! is sometimes violent, following an induction period. However, inverse addition, i.e. slou. addition of phenylacetic acid to the fuming nitric acid at 25-35°C followed by heating under reflux for 1 hr has proved satisfactory. Material far class use has also been prepared by the method of reference (8). To obtain a satisfactory nmr spectrum in acetone, thorough drying (e.g., 70% 6 hr) of the sample is necessary: material not so dried may exhibit the carboxyl resonance at as high as 6.56. 36 1 Journal of Chemical Education
Literature Cited (11 Claret. P. A,. "Qualitative Organic Analysis.'' Pitman and Sons. Ltd.. London. 1951. 12) Donaruma. L. G.. and Heldt. W. Z.. "Oreattie Reactions," John Wiley and Sons. Inc.. NewYork, II1II. Vol. 11. p. I. 131 K8daba.P. K.. T#rohedron. 22.2453 119661. (4) Koneford. .I R.. and Simpson..l. C. E . . J Cham. Sor.. 3541l9481. 161 Rmwn. E. L.. and Campbell, N . . J Chsm S o c lb991193ii. 161 Morley. J. S.. Simp~on.J.C. L a n d Stephenson. 0 . ; Chem. S n c , 1717 119481. lil Romhe. W..RPI. Umt. C h e m C.5. I?. LSlO119091. IR! UcGhie, .I. F.. Morton. C.. Reynolds. B. L.. and Spence. d . W.. J Soc Chsm ind ILondnn1.PR.92R 11969). 191 Radr~srewrki.R.. Re? Orut Chrm. Csa.. 3. MR 11670;.
