CONTENTS
I.Organic qualitative analysis (Scheme of organic
analysis)
II. Multistep synthesis
(a). Benzoic acid – m- nitrobenzoic acid - Methyl m-Nitrobenzoate (b). Aniline -acetanilide- p-bromoacetanilide- p-bromoaniline (c). Synthesis of dibenzal acetone by Aldol condensation (d). Synthesis of methyl orange by coupling reaction.
III. Organic Estimations
(a). Estimation of Aniline/ Phenol (b). Estimation of Ester
(c). Estimation of iodine value of Ester
(d). Estimation of Saphonification value of an oil/fat (e). Estimation of Glucose using Fehling Solution
INSTRUCTIONS
Chemistry is a discipline based on observation. In lecture you will learn principles and theories and in laboratory you have opportunity to experience these principles and theories in practice. The following section presents some general guidelines. Making laboratory safety important.
Kindly follow the guidelines given below:
Laboratory aprons must be donned at all times in the lab and put up hair properly.
Sandals, open-toed shoes and high heels are not permitted in the laboratory.
Shorts or skirts cut above the knee are not permitted in the lab.
Never wear cloth that hangs.
Kindly follow the general behaviour listed:
Strictly avoid the use of regional languages in the lab.
No food or beverages will be permitted inside the lab.
Always read the upcoming experiments carefully and thoroughly, being used to understand all of the directions before entering the lab.
Be in and ready, promptly when the lab begins.
Always read the labels of the reagents and never use a reagent from an unlabelled bottle.
Never smell a chemical straight out of the container.
Never pour a waste chemical into drain or put in the garbage.
Never pick broken glassware with your bare hands, regardless of the size of the piece. Please place all broken glassware in the appropriate broken glassware bucket.
Should any injury occur regardless of how minor it is report it immediately to the Lab tutors.
Wash your hand frequently during the lab and definitely wash your hand twice at the end of the lab.
QUALITATIVE ORGANIC ANALYSIS
SCHEME OF ORGANIC ANALYSISThe Scheme of Analysis may be divided into five parts 1. Preliminary tests
2. Detection of elements
3. Detection of Characteristic groups 4. Confirmatory tests
5. Confirmation by preparing a solid derivative for identifying the organic compound.
Experiment Observation Inference
I Preliminary tests
1. Colour and appearance of the substance are noted
2. Odour is noted
3. Solubility is noted
A little of the given compound is shaken with the following solvents
(a) Cold water
(b) Sodium hydroxide
(c) Dil.Hydrochloric acid
(a) Colourless (b) Yellow
(c) Brown or black (a) Pleasant fruity
(b) Fishy or ammoniacal (c) Kerosene like smell (d) Bitter almond smell (e) Pungent (f) Carbolic soluble Insoluble Soluble in sodium hydroxide and reappears as turbidity on adding excess of dil. HCl. Soluble and reappears as turbidity on adding excess of NaOH solution
Presence of hydrocarbon, aldehydes, ketones, acids esters etc.
Presence of aromatic nitrocompounds
Presence of phenol or amine Presence of ester
Presence of amines Presence of hydrocarbon
Presence of benzaldehyde of nitrobenzene
Presence of halogen compounds Presence of phenol
Presence of sugars, lower aliphatic alcohols, aldehydes, ketones and esters.
Presence of aromatic hydrocarbons, amines, phenols, higher aldehydes, ketones and esters.
Presence of acids or phenols.
II. Detection of Elements. Lassaigne’s Test. A small piece of metallic sodium is melted in an
ignition tube by gentle heating. Then small quantity of the substance is added. It is again heated gently to complete the reaction and then strongly. When the ignition tube is red hot it is plunged into distilled water taken in a china dish. The tube breaks and any residual sodium react with water. The broken ignition tube is ground well with the bottom of a boiling tube. The mixture is boiled well and filtered and the filterate is known as the sodium fusion extract. The following tests are done with the extract.
1 To one portion of the sodium fusion extract half of its volume of freshly prepared ferrous sulphate solution is added, boiled, few drops of ferric chloride solution is added and acidified with dil hydrochloric acid
A blue or green colouration or precipitate is obtained
Nitrogen is present
2 Another portion of the extract is acidified with dil. Nitric acid, boiled well, cooled and silver nirate solution is added
(a) White curdy precipitate soluble in ammonia
(b) Yellowish white precipitate sparingly soluble in ammonia (c) yellow precipitate insoluble in ammonia Chlorine is present Bromine is present Iodine is present. 3. To the third portion of the extract a
few drops of freshly prepared sodium nitroprusside solution is added
Violet colouration Sulphur is present.
III DETECTIONOFCHARACTERISTICGROUPS
1 Test to find whether aliphatic or aromatic (i)Ignition test. A small quantity of the substance is ignited on nickel spatula
(ii) Nitration test: A little of the substance is added to a mixture containing 2mL con. Sulphuric acid and 1mL con. Nitric acid taken in test tube. It is then heated on a boiling water bath for about half an hour and then poured into cold water taken in the beaker
(a) Burnt with a non-smoky flame
(b) Burnt with a smoky luminous flame Colourless solution Yellow solution or precipitate Presence of aliphatic substance Presence of aromatic substance Presence of alphatic substance Presence of aromatic substance.
2 Test to find out whether unsaturated or saturated (i) Action of dilute potassium
permanganate: A little of the substance is shaken with water and
(a) Immediate decolourisation
Presence of unsaturated compound
one or two drops of dil. potassium permanganate solution
(ii)Action of bromine water: A little of the substance is dissolved in suitable solvent( alcohol/ water) then a little bromine water is added (iii) Action of bromine in
carbontetrachloride: A little of the substance is dissolved in carbon tetrachloride and bromine in carbon tetra chloride is added and shaken
(b) Slow decolourisation
Decolourisation without the formation of a precipitate. No decolurisation
(a) Decolourisation without the evolution of hydrogenbromide
(b)Decolourisation with the evolution of hydrogen bromide (c) Decolourisation with formation of a precipitate. Presence of easily oxidizable substance like phenol, niro phenol, amines, belnzaldehyde, etc. Presence of unsaturated compound. Presence of saturated compound. Presence of unsaturated substance Presence of saturated substances Presence of easily brominated compounds like phenols, aromatic amines etc.
3 Action of con. Sulphuric acid: A little of the substance is warmed with con.H2SO4
(a) Charring with effervescence due to the liberation of sulphurdioxide, carbondioxide,
carbonmonoxide and smell of burnt sugar
(b) dissolves gradually on heating
(c) White precipitate which dissolved in excess of acid
Presence of carbohydrate Presence of aromatic hydrocarbon Presence of basic substance like aromatic amines 4 (1) Action of sodium hydroxide
solution: A little of the substance is boiled with dilute sodium hydroxide solution
(a) Ammonia is evolved (b) substance dissolved
(c)Separation of oil or formation of an emulsion (d)Solution turns deep yellow in colour
Presence of amide Presence of acidic substances like acids phenols and their derivatives
Presence of anilides Presence of
(2)The given compound is boiled with 20% sodium hydroxide for half an hour then cooled and acidified with dilHCl
White precipitate
Presence of aromatic esters and amides
5 Action of Sodalime: A little of the substance is mixed with thrice its mass of dry sodalime in a dry test tube and heated. The smell of the issuing gas is noted.
(a) Ammonia gas is evolved (b) Kerosene lie smell
Presence of amides and amines
Presence of acids 6 Action of sodium bicarbonate: to
one mL saturated solution of sodium bicarbonate solution little of the substance is added
Brisk effervescence of carbondioxide
Presence of acids
7 Action of Metallic Sodium: To a little of the substance ( if solid dissolve in dry benzene) in a dry test tube a small piece of metallic sodium is added
Brisk effervescence Presence of alcohols, acids and phenols. 8 Action of ferric chloride solution:
To a little of the substance in Water or alcohol a few drops of neutral ferric chloride is added
(a) Violet colour
(b) A flocculent white precipitate
(c) green colour changing to a white precipitate
(d) Buff coloured precipitate
Presence of phenol Presence of α- naphthol Presence of β-naphthol Presence of benzoic acid, cinnamic acid or phthalic acid
9 Action of Borsche’s reagent: To one mL of Borsche’s reagent a little of the substance is added and heated over a water bath for five minutes. Cooled and little water is added
A yellowish orange precipitate is obtained
Presence of aldehydes or ketones
10 Action of Schiff’s reagent: A little of the substance is added to 1mL Schiff’s reagent taken in test tube and shaken well
Violet colour developed within two minutes
Presence of aldehydes
11 Action of Tollen’s reagent: A little of the substance is added to about 2ml tollen’s reagent in a clean test tube and heated in a boiling water bath
(a) Black or brown precipitate
(b) Bright silver mirror is formed
Presence of polyhydric phenol Presence of
aldehydes, reducing sugars such glucose, fructose, maltose etc. 12 Action of Fehling’s solution:
Fehling’s solution A and Fehling’s solution B are mixed in equal volumes. To 1 mL of this reagent a little of the organic compound is added and heated on a boling water bath
Reddish brown precipitate is formed
Presence of
aldehydes, polyhydric phenols, and reducing sugars.
13 Action of Molish’s reagent: To a solution of substance in water added a few drops of alcoholic solution of α-naphthol. Then added about 1mL of con.H2SO4 along the sides of the test tube without disturbing
Violet ring is formed at the junction
Presence of Carbohydrates.
IV Confirmatory Tests
A If nitrogen is present is present, the following tests are conducted. Besides the following tests for those groups for which indications are got are also done.
1
2
Action of sodium hydroxide solution. A little of the substance heated with sodium hydroxide Action of Soda-lime: A little of the organic substance is heated with excess of dry soda-lime
(a) Ammonia is evolved (b)Separation of oil and formation of an emulsion (a) Ammonia is evolved (b) Amine is roduced Presence of amides Presence of anilides Presence of amides and amines Presence of aminoacids, toluidines and anilides
3 Biuret test:A little of the substance
is gently heated in a dry test-tube until it melts and then solidifies. The residue is dissolved in a little water and a dilute solution of copper sulphate is added followed by sodium hydroxide solution drop by drop.
A violet colour is produced. Presence of diamide like urea.
4 Action of nitrous acid: A little of the substance is dissolved in dilute hydrochloric acid, cooled in ice water and a 10%solution of sodium nitrite is added with shaking till it is slightly in excess.
(a) Liberation of nitrogen with the formation of alcohol.
(b) Separation of yellow oil. (c) Reddish brown solution is obtained. Presence of aliphatic primary amines. Presence of secondary amines Presence of tertiary amines
5 With the solution obtained above the following tests are done.
(i)To one portion of the solution an alkaline solution of β-naphthol is added.
(ii)A portion of the solution is extracted with ether. The ether extract is washed with sodium hydroxide solution and then with water. The ether is evaporated off and Liebermann’s nitroso reaction is conducted with the residual oil. (iii)To another portion, dilute
A scarlet red precipitate is formed.
Blue or green solution is obtained.
Ether layer becomes deep
Presence of aromatic primary amines. Presence of secondary amines.
sodium hydroxide solution is added and then shaken with little ether.
green. amines.
6 Carbylamine reaction. To a little
of the substance few drops of cholorofm and about 2ml of alcoholic potash are added and warmed.
Offensive smell is produced Presence of primary amine
7 Mulliken and Barker’s reaction. A little of the substance is dissolved in alcohol. A few drops of calcium chloride solution is added and pinch of zinc dust. Boiled for five minutes, cooled and filtered into a tube containing Tollens reagent.
Bright silver mirror or black precipitate is obtained.
Presence of nitro group.
8 Reduction of nitro group to amino group. A little of the substance is treated with few ml of dilute hydrochloric acid and a pinch of zinc dust. Heated for some time and filtered. With the filtrate the following tests are done.
(a) Carbylamine test is done with one portion of the filtrate
(b) To another portion of the filtrate dil. hydrochloric acid is added, cooled in ice and sodium nitrite solution is added in excess. Then alkaline β-naphthol solution is added An offensive smell is produced A scarlet precipitate is obtained Presence of nitro group Presence of aromatic nitro group.
B If halogen is present, the following tests are conducted. Besides the following tests, tests for those groups for which indications are got also done
1 Action with litmus. A little of the substance is shaken with hot water and tested with litmus
(a) soluble and acidic to litmus
(b) Insoluble and acidic
(c) Insoluble and neutral
Aliphatic halogen substituted acids Presence of aromatic halogen substituted acids Presence of halogen substituted hydrocarbons, ketone etc.
2 Action with silver nitrate solution. A little of the substance is boiled with sodium hydroxide solution for 15 minutes. Cooled, acidified with dil. nitric acid and then added silver
(a) Precipitate of silver halide is formed
(b) No precipitate of silver
Halogen is in the side chain
nitrate solution. halide nucleus 3 Action of alcoholic silver nitrate.
To a little of the substance 2 ml of alcoholic silver nitrate solution is added and warmed gently.
(a) Precipitate of silver halide is obtained
(b) No precipitate of silver halide
Presence of halogen in the side chain Presence of halogen in the nucleus.
C If sulphur is present, the following tests are conducted. Besides the following tests, the tests for those groups which indications are got also done.
1 Action of alcoholic sodium hydroxide To a little of the substance 2 ml of alcoholic sodium hydroxide solution is added and warmed gently.
Ammonia is evolved Presence of thiourea or sulphonamide 2 Action of con. Hydrochloric acid.
To a little of the substance 2 ml con. HCl is added and warmed gently.
Pungent smell Presence of
substituted thiourea. 3 Fusion with alkali. A little of the
substance is fused with sodium hydroxide dissolved in water anf hydrochloric acid is added
(a) Hydrogen sulphide is evolved
(b) Sulphurdioxide is evolve with the formation of phenol (c) No phenol is formed but precipitate of barium sulphate when barium chloride is added
(d) Ammonia is evolved during fusion. No phenol is formed. Sulhur dioxide is evolved on adding acid
Presence of thio urea Presence of sulphonic acid Presence of amino sulphonic acid Presence od sulphonamide
D. If nitrogen, halogens and sulphur are absent, tests for the following groups for which indications are got, are done.
I.Aldehydes
1. Schiff’s reagent test is conducted
Violet colour is obtained Presence of aldehydes. 2 Borsche’s reagent test is
conducted.
Note: Ketones also answer this test.
A yellow precipitate is obtained.
Presence of aldehydes.
3 Tollen’s reagent test is
conducted.
Note: Other reducing reagents also answer this test.
Bright mirror or black precipitate is obtained.
Presence of aldehydes.
4 Fehlling’s solution test is
conducted.
Note: Other reducing reagents also
answer this test
5 Sodium bisulphite test is conducted: A little of the
substance is added to a saturated solution of sodium bisulphite and shaken well.
Note: ketones also answer this test.
White crystalline precipitate is obtained.
Presence of aldehydes.
6 Semicarbazide test: Dissolved 0.5g of semicarbazide hydrochloride in 5ml of water and added 0.5g of anhydrous sodium acetate. It is warmed to get a solution. Then added a small quantity of the substance and warmed on a water bath.
Note: ketones also answer this test.
White crystalline precipitate is obtained.
Presence of aldehydes.
II. Ketones.
1 Borsche’s reagent test is conducted.
A yellow precipitate is obtained.
Presence of ketones. 2 Semicarbazide test is conducted. White crystalline
precipitate is obtained
Presence of ketones. 3 Sodium bisulphate test is
conducted.
White crystalline precipitate
Presence of ketones
4 Iodoform test is conducted: 0.25ml of acetophenone is taken in a test tube.Add 1.5ml of NaOH solution followed by I2-KI solution until the iodine colour persisted on shaking. The solution is warmed. Excess of iodine solution is removed by adding dil.NaOH solution drop by drop.The contents is allowed to stand in the water bath for 20minutes.
Yellow precipitate with characteristic odour is formed
Presence of ketones containing the CH3 -CO-group
III.Acids
1 Tested with sodium bicarbonate solution.
Effervescence Presence of acids. 2 Sodalime test is conducted Kerosene smell
obtained
Presence of acids. 3 Ester formation test is conducted.
About 0.5g of the substance is heated gently with about 1 ml of
ethanol and few a drops of conc.sulphuric acid for about 1 minute. Cooled and poured into a few ml of water in test-tube.
4 s-Benzylthiouronium salt test:
About 0.25 g of the acid is dissolved in 2 ml of warm water. The acid is neutralised by adding a few drops of NaOH solution (phenolphthalein can be used as an indicator) .Then 2 drops of NH4Cl are added followed by 0.5 g of s-Benzylthiouronium chloride in 2ml water. It is cooled in ice.
White crystalline precipitate.
Presence of acids
5 Fluorescein reaction. Fused together in a dry test-tube a small quantity of the substance with an equal amount of resorcinol after moistening the mixture with two drops of conc. Sulphuric acid. Cooled, dissolved in water and then added excess of sodium hydroxide solution.
A reddish solution having an intense green fluorescence is produced.
Presence of dicarboxylic acids.
IV.Phenols
1 Neutral ferric chloride solution test is conducted. A little of the substance is treated with neutral ferric chloride solution.
(a) Violet blue or green colour. (b) A flocculent white precipitate. Presence of phenol. Presence ofα-naphthol. 2 Liebermann’s nitroso reaction: To
two drops of melted phenol, added little solid NaNO2 . Heated gently for 1 minute.Cooled and added 4 drops of conc.H2SO4. Diluted cautiously with water.
Red solution which turned to green or blue on adding sodium hydroxide solution.
Presence of phenol.
3 Phthalein fusion reaction: About 2
drops of melted phenol is mixed with a small quantity of phthalic anhydride in a dry test-tube. 2 drops of conc.H2SO4 are added. The mixture is heated at about 150oC for 2 min.Cooled and exess of 10 %
Red, bluish-purple, blur green fluorescene, green or very faint green colouration.
Presence of phenol.
NaOH solution is added.
4 Benzoylation (Schotten Baumann reaction) is conducted :Dissolved
about 0.25 g of phenol in about 5ml of 10 % NaOH solution contained in a boiling tube . About 1 ml of benzoyl chloride is added. The boiling tube is corked and shaken vigorously for about 15 min.
Crystalline white precipitate. Presence of phenol.
5 Azo-dye formation reaction:
Dissolved 2 drops of aniline in 1 ml dil. HCl and well cooled in ice. A few drops of saturated NaNO2 solution are added. The diazonium solution thus obtained is added to a well cooled solution of phenol in aqueous NaOH solution.
Orange, scarlet,dark red, brownish red solution or precipitate is obtained.
Presence of phenol.
V. Alcohols.
1 Test with metallic sodium is conducted. Brisk effervescence. Presence of alcohols. 2 Acetylation test: A little of the substance
is heated with glacial acetic acid and few drops of conc. Sulphuric acid. Then cooled and poured into excess of water containing little sodium carbonate solution.
Pleasant fruity smell is produced.
Presence of alcohol.
VI. Esters.
1 Hydrolysis. A little of the substance is refluxed with concentrated solution of sodium hydroxide and then acidified with conc. Hydrochloric acid.
White precipitate is formed.
Presence of ester.
2 Hydroxamic acid formation. To a few
drops of the substance, added 0.2g of hydroxylamine hydrochloride and about 5 ml of 10% sodium hydroxide solution and the mixture gently boiled for 2 minutes. Cooled and acidified with dilute hydrochloric acid and then added a few drops of ferric chloride solution.
A violet or a deep
red-brown colour
developed immediately
Presence of ester
VII Carbohydrates.
1 Concentrated sulphuric acid test is conducted. Warmed a little of the
substance with conc. Sulphuric acid.
Charring with smell of burnt sugar
Presence of carbohydrate.
2 Sodium hydroxide test is conducted.
A little of the substance is boiled with sodium hydroxide solution
Solution turned yellow or brown. Caramel smell is emitted
Presence of carbohydrate. 3 Molisch’s test is conducted. A deep violet ring is
formed.
Presence of carbohydrate. 4 Treated with Tollen’s reagent Bright silver mirror or
black precipitate.
Presence of reducing sugar.
5 Fehling’s solution test is conducted: Warmed with Fehling’s solution.
Red precipitate is formed.
Presence of reducing sugar.
6 Osazone test is conducted: About 1 g
of sugar is dissolved in 15 ml water and add 4 g of phenyl hydrazine hydrochloride, 4 g of sodium acetate and 1 ml glacial acetic acid. Heated for 15 minutes in a water bath.
Yellow crystals are formed.
Presence of carbohydrate.
VIII. Hydrocarbons.
1 Odour is noted. Kerosene like smell
observed.
Presence of hydrocarbons. 2 Sulphonation is conducted : To 1 ml of
fuming H2SO4 contained ina test tube, 2 drops of the substance are added and shaken well for 3 min.
Substance has gone into solution.
Presence of hydrocarbon.
3 Nitration is conducted.
Note.(1) To nitrate naphthalene, about 0.5g of naphthalene is dissolved in 2 ml of glacial acetic acid by gently warming, cooled and heated to 800c after adding conc. Nitric acid. It is then poured into water when yellow crystals separate.
Yellow solid obtained.
Presence of hydrocarbon is confirmed
4 Picrate test is conducted : Saturated
solutions of naphthalene and picric acid, both in benzene are prepared separately. These two solutions are mixed in a watch glass and allowed to evaporate.
Red or yellow precipitate.
Presence of polynuclear hydrocarbons.
5. Confirmation by preparing a solid derivative
The final step in the analysis of a sample organic compound is the preparatioof a suitable solid derivative.
Preparation of Derivatives
Derivatives for Aromatic Hydrocarbons.
The main reactions carried out for the preparation of derivatives for aromatic hydrocarbons are (a) nitration (b) side chain oxidation and (c) preparation of picrates for polynuclear hydrocarbons.
(a) Nitration. Nitroderivatives can be prepared for benzene, toluene etc. About 1 ml of fuming
nitric acid and 1 ml of conc.sulphuric acid are mixed.About 0.25 ml of benzene or toluene is added to the nitrating mixture. Then the mixture is heated on a boiling water bath for half an hour,till a drop of mixture poured into water crystallizes immediately. The mixture is then poured into cold water taken in beaker and stirred well. The crystals are filtered at the pump,recrystallised from dilute alcohol, dried and then melting point is noted.
(b). Side chain oxidation. For aromatic hydrocarbons containing side chain like toluene or side
chain like xylenes, side chain oxidation can be effected for the preparation of their derivatives. About 0.25 ml of the substance is mixed with about 12.5 ml of saturated potassium permanganate solution and 1 g of anhydrous sodium carbonate. The mixtutre is then boiled for half an hour under reflux. It is then transferred to a beaker, acidified with conc. Hydrochloric acid and then added a saturated solution of sodium sulphite until the brown precipitate of manganese dioxide has dissolved. It is cooled, filtered at the pump and recrystallised from hot water. It is dried and melting point is noted.
(c) Picrates. Picrates can be easily prepared for polynuclear hydrocarbons like naphthalene
anthracene ctc About 0.25g of picric acid is also dissolved in hot benzene. About 0.25g of picric acid also dissolved in hot benzene. These two solutions mixed well, poured into a watch glass and kept for sometime. Coloured crystals of picrate separate. Melting point is noted.
Derivatives for Halogen compounds of Aromatic hydrocarbons.
(a) Nitration. For compounds having halogen in the nucleus like chlorobenzene, ortho-chloro toluenes, para-dichlorobenzene etc. nitroderivatives are prepared. Nitration is carried out in the same manner as aromatic hydrocarbos. Melting point is noted.
(b) Side chain oxidation. For compounds having halogen in the side chain like benzyl chloride and for nuclear halogen compounds containing side chain oxidation can be adopted.Side chain oxidation can be adopted exactly in the same manner as explained under aromatic hydrocarbons. Melting point of the derivatives is found out.
Derivatives for alcohols.
The following derivatives can be prepared for alcohols.(a) benzoates and (b) oxidation products.
(a) Benzoylation(Schotten- Baumann reaction). About 0.25 g of the substance is dissolved in
about 4 ml of 10% sodium hydroxide taken in a boiling tube. About 0.5 ml benzoyl chloride is added, corked the tube well and shaken vigorously for about 15 minutes.. (till the smell of benzoyl chloride is no longer perceptible). Filtered, washed several times with water. Dried and then recrystallised from alcohol. Melting point is determined.
(a) Oxidation. Side chain oxidation can be carried out in the case of alcohols like benzyl
alcohol. It is same as in the case of aromatic hydrocarbons
Derivatives for phenols.
The following derivatives can be prepared for phenols. (a) benzoyl derivatives (b) bromination products (c) Nitration products and (d) picrates
(a) Benzoylation. Benzoylation can be easily carried out for phenols, cresols, α- naphthols, β-
naphthols and resorcinol. Details of benzoylation, refer under the derivatives of alcohols.
(b) Bromination. Bromination can be done in the case of phenols and cresols. A bout 0.25 g of phenol is treated with saturated bromine water till the yellow colour due to excess of bromine persists. The mixture should be shaken well after each addition of bromine water. The
crystallized bromo derivative is filtered at the pump, washed with water and dried. It is recrystallised from alcohol, dried and melting point is determined.
(c) Nitration. Poly nitro derivatives can be prepared for certain phenols. About 0.25 g of phenol
is dissolved in about 1 ml of cold conc. Sulphuric acid and the solution poured slowly into about 6 ml of the nitrating mixture, containing equal volumes of concentrated nitric acid and sulphuric acids. Then it is warmed for a few minutes on a water bath. If the reaction is violent and there is tendency to form tarry matter, it has to be cooled in ice without warming on the water bath. Cooled poured into ice water, filtered and recrystallised from dilute alcohol containing a few drops of conc. Hydrochloric acid.
(d) Picrates. Picrates can be easily prepared for phenols. Details refer under derivatives of
hydrocarbons.
Derivatives for aldehydes and ketones.
The important derivatives for aldehydes and ketones are: (a) Phenyl hydrazones(b) 2,4- dinitro-phenyl hydrazones (c) semicarbazone and (d) oximes.
(a) Phenylhydrazones. A solution of phenylhydrazine is prepared by dissolving 0.5g of phenylhydrazine hydrochloride and 0.75 g of sodium acetate in 5 ml of water. About 0.25g of aldehyde or ketone is dissolved in a little of alcohol and added to phenyl hydrazine solution. If a clear solution is not obtained, more alcohol is added. The mixture is heated on a water bath for about half an hour. The phenyl hydrazone is separated on cooling. It not a few drops of water are added. The product is filtered off and crystallized from alcohol. The melting point is determined.
(a) 2,4- dinitrophenylhydrazones. Benzaldehyde acetophenone and benzophenone readily form
2,4- dinitrophenylhydrazones with 2,4- dinitrophenyl- hydrazine.(Borsche’s reagent). About 0.25 g of substance is diossolved in methanol. It is mixed with about 1 ml of Borsche’s reagent and shaken vigorously for a few minutes, with scratching if necessary. If the yellowish orange hydrazone does not separate, the solution is heated in a got water bath for about 10 minutes. It is cooled, filtered at the pump, recrystallised from alcohol and melting point is determined.
(b) Semicarbazones. About 0.25 g of asemicarbazide hydrochloride is added to 2.5 ml of water followed by 0.25g of anhydrous sodium acetate and warmed gently until a clear solution is obtained. A solution of 0.25 g of the substance in 1 ml of methanol is added and warmed on a water bath.It is cooled. Crystals of semicarbazone filtered and washed with water. It is recrystallised from alcohol, dried and the melting point determined.
(c) Oximes. About 0.25 g of hydroxylamine hydrochloride is dissolved in about 2 ml of water. About 0.25 g of sodium acetate and 0.1g of the compound are added into it. In case the compound is water insoluble, sufficient amount of alcohol is added to the mixture to give a clear solution. The mixture is then heated on a water bath for about 15 minutes and then cooled in ice.Precipitation may be induced by adding a few drops of water. Filtered, washed with cold water, recrystallised from dilute alcohol or benzene, dried and melting point is determined.
Derivatives for Acids.
The following derivatives can be prepared for carboxylic acids (a) s- benzylthiouronium salts (b) amides (c) anilides (d) bromo-derivatives (e) nitration and (f) acid anhydride.
(a) s- Benzylthiouronium salts. Dissolved about 0.2g of the acid in the minimum amount of hot water, 5% aqueous sodium hydroxide solution is added until the solution is just alkaline to methyl orange.Then one drop of dilute hydrochloric acid is added. The sodium salt of the acid thus prepared is poured into a solution of 0.3g of s-benzylthiouronium chloride in 3ml of water.The mixture is stirred and cooled in ice bath.Crystals are filtered at the pump, recrystallised from ethanol containing 10% of water, dried and melting point determined.
(b) Amides. Amide derivatives can be easily prepared for benzoicacid, phthalic acid, cinnamic
acid and salicylic acids. About 0.5g of the acid is mixed with an equal quantity of phosphorous pentachloride in a mortar. The mixture is ground well till the evolution of fumes ceased. Then added a few ml of concentrated ammonia.Stirred well and some water is added. The amide formed is filtered at the pump, washed with water and dried. It is recrystallised from dilute alcohol and melting point is determined.
(c) Anilides. About 0.4g of pure aniline are taken in a dry test tube.The mixture is boiled under reflux for about an hour,cooled and poured in an excess of dilute hydrochloric acid. It is filtered at the pump, washed with water and dried.It is then recrystallised from dilute alcohol and melting point determined.
(d) Bromo derivatives. Bromo derivatives can be easily prepared for cinnamic acid. About 0.25g of the acid is dissolved in boiling water. Excess of bromine water is added till brown colour persisted. Crystals formed are filtered, washed with water and dried. Melting point determined.
(e) Nitration. Nitro derivatives can be easily prepared for benzoic acid, salicylic acid etc.1ml of nitrating mixture is prepared by mixing equal volumes of conc. nitric acid and conc.sulphuric acid. About 0.25 g of the acid is added into the nitrating mixture in small portions at time with shaking. It is then heated on a water bath for about 30 minutes. It is cooled and poured into water. It is filtered at the pump, washed with water and dried. The melting point is determined. (f) Acid anhydride. Anhydried can be prepared for ortho- carboxylic acid like phthalic acid. About 0.25 g phthalic acid taken in a dry china dish and covered by means of an inverted funnel.the stem of the funnel is closed by means of cotton wool. The china dish is gently heated. Phthalic anhydride is formed which gets collected at the cooler side of the funnel. After cooling the funnel is removed and the anhydride collected. The melting point of the anhydride is then determined.
Derivatives for Esters.
The important method used for the preparation of derivatives of esters is hydrolysis to the corresponding acid.
(a) Hydrolysis. About 1 ml or 1 g of the ester is mixed with about 10 ml of 20% solution of sodium hydroxide in a R.B flask and boiled under reflux for about 45 minutes. It is then transferred to abeaker, cooled and acidified with conc. Hydrochloric acid. The acid precipitated is filtered at the pump. Washed with cold water and dried. Melting point is determined.
Derivatives of Amines.
The following derivatives may be prepared for primary and secondary amines.(a)acetyl derivatives (b)benzoyl derivative and (c)picrates.In the case of tertiary amines, picrates are commonly prepared.
(a) Acetylation. Since acetyl derivatives of aliphatic amines are usually soluble in cold
water,acetylation can be carried out in the case of aromatic amines like aniline ,toluidines,N-methyl aniline etc.About 0.5 ml of the amine ,if liquid or 0.5g,if solid is taken in a small R B flask or boiling test tube fitted with a reflux condenser.About 2.5ml of acetic anhydride and acetic acid mixture (equal volumes) is added and refluxed gently for 15 minutes.It is then poured into water.The solid anilide separated is filtered at the pump,washed with water and dried.It is recrystallised from dilute alcohol and melting point is noted.
(b) Benzoylation.Benzoyl derivative can be prepared for primary amines like aniline, toluidines
and for secondary amines like N-methyl aniline.Details of benzoylation refer under preparation of derivatives for phenols.
(c) Picrates.Picrate derivative can be prepared for primary,secondary(except diphenyl amine)
cold ethanol to get saturated solutions.The two solutions are mixed and poured into a watch glass.Coloured crystals of picrate separate.Melting point is determined.
(d) p-Nitroso derivative. p-Nitroso derivative can be prepared for the tertiary
amine,N,N-dimethylaniline.About 0.5 ml of N,N-dimethylaniline is dissolved in about 4ml of dilute hydrochloric acid.It is cooled in ice and the added about 2ml of 20%sodium nitrite solution in drops.It is kept in ice bath with stirring for 5 minutes.Then dilute sodium hydroxide solution is added.A green precipitate of p-nitrosodimethylaniline is obtained.It is filtered at the pump ,dried and melting point is determined.
Derivatives for Nitro Compounds.
The important derivatives for mononitro-compounds are: (a) The nitro group is reduced to primary amino group.The primary amine obtained by reduction, can be diazotized and coupled as explained under preparation of derivatives for phenols.If aromatic primary amine is obtained by reduction,it can be diazotized and coupled with β-naphthol in alkaline solution (b) Further nitration to get solid dinitro compounds (c) In the case polynitro compounds, they can be partially reduced to solid nitroanilines and hence partial reduction serves a method for the preparation of derivative for polynitro hydrocarbons.
(a) Reduction of mono-nitro compounds. As already explained, mono- nitro compounds are
reduced to the corresponding primary amino compounds and with the amino compound benzoylation and azodye formation conducte.
(b) Nitration. Nitration of benzene to solid meta-dinitrobenzene can be easily carried out.1ml of
conc.nitric acid and 1ml of conc.sulphuric acid are mixed together in a boiling test-tube.About 0.25ml of nitrobenzene is added with shaking. The mixture is heated in a boiling water bath for about 15 minutes.It is then poured into cold water. It is filtered at the pump,washed with water and dried.It is recrystallised from alcohol and melting point is noted.
(c) Reduction of polynitro hydrocarbons to aminonitro hydrocarbons. This method is used
for the preparation of derivative for meta-dinitrobenzene.About 0.5g of powdered sulphur is added to a solution of 1.5g of sodium sulphide in about 7ml of water. The mixture is boiled until a clear solution is obtained.
About 1g of meta-dinitrobenzene is boiled with about 50ml of water in a beaker. To the boiling solution is added the sodium sulphide solution prepared above, in a thin stream with stirring.When the addition is over, the mixture is boiled for about 30 minutes more and filtered hot.The filtrate is cooled when meta-nitroaniline separates. It is filtered at the pump, washed with cold water and dried. It is then recrystallised from hot water, dried and melting point is determined.
Note:(i)For nitrophenols,benzoylation does not proceed smoothly and hence nitrophenols are
reduced to aminophenols and then benzoylation is conducted (methods of reduction and benzoylation already explained)to obtain dibenzoyl derivative.(ii) For nitroaniline, benzoyl derivatives can be prepared.
Derivatives for Amides.
For amides other than urea,hydrolysis can be effected for the preparation of derivative. If the original compound is an aromatic amide, alkaline hydrolysis followed by acidification with hydrochloric acid gives a solid organic acid with definite melting point.In the case of aliphatic amides, the acid obtained after hydrolysis will remain in solution. In such case, the cold solution, when carefully neutralized and treated with s-benzylthiouronium chloride, deposits the thiouronium salt.
(a) Hydrolysis. About 1 g of aromatic amide is taken in a R.B flask fitted with a reflux
minutes. It is cooled and acidified with conc. Hydrochloric acid. The precipitated acid is filtered at the pump, washed, recrystallised from hot water, dried and melting point determined.
Derivatives for Urea
(a) Urea nitrate. A concentrated solution of urea in about 1 ml of water is prepared. Then a few drops of conc. Nitric acid are added with shaking. White crystalline precipitate of urea nitrate separates. It is filtered at the pump, dried and melting point is determined.
(b) Urea Oxalate. A concentrated solution of urea in about 1 ml of water is prepared. Then add a concentrated aqueous solution of oxalic acid in drop with shaking. White crystalline precipitate of urea oxalate separates. Filtered at the pump, dried and melting point is determined.
Derivative for Thiourea.
s- Benzyl thiouronium chloride. About 0.5 g powdered thiourea and 0.8 ml of benzyl chloride
are added to one ml of 95% ethanol in a small R.B. flask or boiling test tube fitted with reflux condenser. The mixture is warmed on a water bath with gentle shaking until effervescence subside. Then the mixture is boiled under reflux for 30 minutes. The solution is cooled in ice bath when crystals of s-Benzylthiouronium chloride separate. Crystals are filtered at the pump, dried and melting point is determined.
11. Derivatives for Anilides.
The following derivatives can hbe prepared: (a) Hydrolysis to the corresponding acid and amine (b) bromo derivative and nitration. (c) Nitration.
(a) Hydrolysis. Anilides undergo hydrolysis very slowly by alkalies and hence acid hydrolysis
is usually employed. A bout 0.5 g of anilide is mixed with 5 ml of 70% sulphuric acid in a R.B flask or boiling test- tube fitted with a reflux water condenser. The mixture is gently boiled for about 15 minutes. Then the solution is cooled and diluted with about 5 ml of water. By hydrolysis, acetanilide gives liquid acetic acid and liquid aniline. With the aniline obtained, solid derivatives can be prepared and their melting points determined.In the case of benzanilide, solid benzoic acid is obtained by hydrolysis. The solid is filtered, dried and melting point is determined.
(b) Bromination. Little of the anilide is dissolved in acetic acid. Then bromine in acetic acid is
added with shaking until brown colour remained. It is then poured into water. The precipitated p-bromo derivative is filtered at the pump, washed with water and dried. It is recrystallised from alcohol, dried and melting point determined.
(c) Nitration. Anilides are nitrated by using 80% nitric acid at 00 c and then poured into ice cold water. Nitration leads to a mixture of o- nitroderivative and p-nitroderivative. Ortho- derivative is soluble in cold alcohol while para- derivative is insoluble.
12 Derivative for carbohydrates.
Osazone. About 1 g of sugar is dissolved in 15 ml water and add 4 g of phenyl hydrazine
hydrochloride, 4 g of sodium acetate and 1 ml glacial acetic acid. Heated for 15 minutes in a water bath. The osazone formed is filtered, washed with water and dried. It is then recrystallized from alcohol, dried and melting point is determined.
Multistep synthesis
1. Benzoic acid – m- nitrobenzoic acid - Methyl m-Nitrobenzoate Step1:
Electrophilic Aromatic Substitution of Benzoic Acid to Produce m-Nitrobenzoic Acid
Recall from your lecture class that a carboxylic acid would be a meta-director in an electrophilic aromatic substitution reaction. In practice, this nitration reaction can result in the production of quite a bit of the ortho product as well, unless the temperature is kept very cold throughout the reaction. All of the materials that will be used in the experiment are in proportion to the amount of benzoic acid that is being reacted. Not more than 3 g of PhCOOH is used, and record its mass carefully
Overall Reaction: COOH Con. HNO3 Con.H2SO4 COLD NO2 COOH
Benzoic acid m-Nitrobenzoic acid
Mechanism: HNO3 + 2 H2SO4 NO2 + HSO4 + H3O NO2 HSO4 COOH COOH NO2 H H2SO4 NO2 COOH
First, prepare a nitrating mixture (NM) by slowly adding con. H2SO4 to con. HNO3 while cooling it in a small Erlenmeyer flask in an ice/water/salt bath to 0oC or less. Make this NM in proportion to the amount of benzoic acid that will be reacting, although the benzoic acid will not be in this mixture. For each g of benzoic acid, use 1 mL of concentrated H2SO4 and 0.67 mL of concentrated HNO3 to prepare this NM. Keep it cold.
Second, prepare the reaction mixture (RM) in a large Erlenmeyer flask; this container will maximize cooling during the reaction. Add concentrated H2SO4 to the Erlenmeyer and cool it to 00C or less. 2.5 mL of H2SO4 for each gram of benzoic acid is used. Add the benzoic acid
slowly to the H2SO4, keeping the temperature below 00C. During the course of this mixing and the reaction to follow, the RM should stay below 00C and never exceed 50C. When all of the benzoic acid has been added to the H2SO4, it will be rather paste-like.
Now, double-check that the RM is colder than 00C and slowly add the COLD NM to the COLD RM, mixing carefully and keeping it cold. Use a short disposable pipette to transfer it and be sure that the rate of addition allows for efficient cooling; remember that the RM should stay below 0oC and never exceed 50C. Add the NM very slowly at first, but the rate can be speeded up as the reaction proceeds. Use the temperature as a guide. After all of the NM has been added, keep the mixture cold for another 10-15 minutes with occasional stirring.
Finally, pour the mixture over ice/water slurry of about 150 g of ice and 200 mL of water. Stir vigorously and the product precipitates. Filter the product from the mixture, wash well with cold water, and allow it to dry. When the product is completely dry, obtains its mass and calculates the theoretical and percentage of yield for the reaction. Check its purity by mp, IR. The product is usually of sufficient purity to use for the next step, but if that is not the case, recrystallize it from hot water.
Step 2:
Fischer Esterification of m-Nitrobenzoic Acid to Produce Methyl m-Nitrobenzoate
Overall Reaction: Con.H2SO4 NO2 COOH m-Nitrobenzoic acid + CH3OH HEAT NO2 COOCH3 Methyl m-Nitrobenzoate
Mechanism: NO2 C O O H S O O O O H H S O O O O H NO2 C O O H H NO2 C O O H H NO2 C O O H H NO2 C O O H H NO2 C O O H H CH3 O H NO2 C O O H H O CH3 H transf er of proton NO2 C O O H H O CH3 H NO2 C O O H H O CH3 H S O O O O H NO2 C O O CH3
As in the previous step, the amounts of reagents used for this procedure will depend on the mass of m-nitrobenzoic acid that is used in the reaction. Use no more than 3 g of it. It is also critical that the m-nitrobenzoic acid is completely dry, since this reaction is an equilibrium process and water in a wet sample will drive the reaction in the reverse direction, reducing the yield of the product.
For each gram of m-nitrobenzoic acid 8 mL of methanol is required and for each 20 mL of methanol, 1 mL of concentrated H2SO4is required. Consider the total volume of this mixture, and choose a round bottom flask that holds about twice that volume; in other words, choose a flask so that it is about half full. Put the three materials in the proportions described above into the round bottom flask with a couple of boiling chips, and attach a reflux condenser to form a reflux apparatus. Heat to reflux for 1 hour.
Pour the reaction mixture into ice /water slurry (use a total volume of slurry of about 5 times the volume of methanol used) and stir. Once the ice is melted, use suction filtration to isolate the product and wash it with water. The crude product should be recrystallized from
methanol or methanol/water. Once it is completely dry, determine its mass and calculate its theoretical and percent yield. Also, determine its purity by mp and IR.
Multi-Step Synthesis Yield Calculation.
When you carry out a series of reaction steps, you usually want to know the efficiency of the whole process. To do so, you can use the percent yields for each step to compute the overall percent yield. This is easiest to explain with an example. Suppose you carried out four reactions in sequence with the percent yields given below.
Step 1: 87.5%; Step 2: 91.2%; Step 3: 79.3%; and Step 4: 81.9% The overall percent yield is computed as shown, here.
Overall Percent Yield: 0.875 x 0.912 x 0.793 x 0.819 x 100 = 51.8% overall.
Be sure to compute the overall percent yield for the two steps of you synthesis of methyl m-nitrobenzoate.
2. Aniline -acetanilide- p-bromoacetanilide- p-bromoaniline Step 1: Acetylation of Aniline
In the first step we need to put the removable acetyl protecting group on the nitrogen of aniline. The acetyl group is electron withdrawing and it therefore makes the lone pair on the nitrogen less reactive either in an oxidation reaction or a protonation reaction. Bromination of aniline suffers from lack of control. The electron donating amino group activates the ring to such a great extent that usually tribromoaniline is isolated. However, if aniline is converted to acetanilide the monosustitution is easily achieved because the acetamino group cannot activate benzene ring towards electrophilic attack as well as simple amino group does. The acetamino group is less effective in donating electron density to the benzene ring, because the electron pair on the nitrogen atom is delocalized by both the carbonyl group and the phenyl ring. It should be kept in mind, however, that the acetamino group is still an activating group.
2. The acetic acid used in the brominating step causes protonation. Protonation of the nitrogen of aniline makes it a very strong deactivating group, making the aromatic ring less susceptible to reaction and would be a meta director. Another value of the acetyl protecting group is that it is bulky group and preferentially directs the bromination to the para position rather than the ortho position. The full mechanism for the reaction is givenbelow. Acetic anhydride ispartially protonated by the acetic acid. This makes the anhydride an even better electrophile for the nucleophilic nitrogen of aniline. This attacks to form the tetrahedral intermediate, which, after proton transfer, loses acetic acid.
NH2 C O O H3C C H3C O CH3COOH NHCOCH3 Procedure:
Dissolve 4.0 mL of aniline in 10 mL of acetic acid in a 100 mL round bottom flask. To this solution, add 5 mL of acetic anhydride and mix well by swirling. CAUTION: the reaction is exothermic and the flask becomes warm. Add two boiling chips, attach a condensing column and attach the hoses for water cooling. Heat at a gentle reflux for fifteen minutes. After fifteen minutes, allow the flask to cool slightly. Cautiously add 5 mL of cold water through the top of the condenser into the reaction mixture. Boil the solution for an additional five minutes so as
to hydrolyze any unreacted acetic anhydride. After boiling for five minutes, allow the reaction mixture to cool slightly and then pour it slowly with stirring into 30 mL of ice cold water. After allowing the mixture to stand for 15 minutes with occasional stirring, collect the precipitate by suction filtration using your Buchner funnel. Be sure to wet the filter paper before you filter. Disconnect from the vacuum, wash the solid crystals with 10 mL of cold water and
reconnect the vacuum tube for a couple of minutes more so as to dry the product as much
as possible. Transfer the crystals to a watch glass and leave them to dry. Weigh the product and record the yield.
Mechanism C O O CH3 C O H3C C O CH3 O H + C O O CH3 C O H3C H C O CH3 O + C O O CH3 C O H3C H H2N C O H3C O H N H H C O O CH3 H C O H3C C O CH3 O N H C O O CH3 H C O H3C C O CH3 O H NHCOCH3
+
C O CH3 HO Bromination of acetanilide NHCOCH3 Br2Glacial acetic acid
NHCOCH3
Br
Acetanilide the starting reagent in this synthesis is a mild analgesic and a mild antipyretic. The antipyretic properties of acetanilide was discovered by accident when a sample, improperly labeled and thought to be naphthalene was inadvertently administered to a patient in 1886.
N H C H3C O and NH C H3C O N H C H3C O
Place 2.0g of acetanilide in 50mL Erlenmeyer flask. Add 7.5mL of glacial acetic acid and swirl the flask until the solid dissolves. Fill 1:4 (V/V) bromine/glacial acetic acid in a burette and clamp it on the stand. Add about 4.4 mL of the bromine acetic acid mixture drop by drop over a 10 minute period with stirring. Stir the reaction mixture for about 15 minutes to complete the reaction. Pour the reaction mixture into a 250mL beaker containing 60mL water. Rinse the flask with 15mL of water and add this rinse to the beaker. Stir the precipitated solid well with a stirring rod to break up any chunks. The solution is in orange colour due excess bromine. Destroy the excess bromine by adding small portion of sodium bisulphate. Collect the product by vacuum filtration and wash the residue four times with 15mL portions of water. Flow air through the residue for drying. Collect the solid, spread it on a watch glass to dry out. Once dried weigh the crude and recrystallize a small portion from dilute alcohol. Record the melting point, and IR spectrum.
Alternative Green Procedure:
NHCOCH3 NHCOCH3 Br CAN, KBr H2O, EtOH Chemicals Required: Acetanilide - 1 g Potassium bromide - 1 g Ceric ammonium nitrate - 6 g Ethanol - 15 mL
Water - 15 mL
In a 250 ml conical flask acetanilide (1 g) was dissolved in ethanol (15 ml). Then potassium bromide (1 g) and ceric ammonium nitrate (6 g) were dissolved in water (15 ml). This solution was transferred into an addition funnel. This solution was added drop wise to the conical flask containing acetanilide solution. After the addition was over, the reaction mixture was stirred for 10 minutes in room temperature (white crystals appeared). Then this solution was poured into ice-cold water. The white crystals were filtered through Buchner funnel and the solid was dried.
Yield: 1.34 g (85 %)
M.p. of p-bromoacetanilide = 165 o
Mechanism: Ce(IV) + Br H2O [Br ] Ce(IV) [Br ] NHCOCH3 NHCOCH3 [Br ] H Br -H NHCOCH3 Br Preparation of p-bromoaniline NH Br H3C O (1) H+/H2O (2) OH NH2 Br
Transfer all of the crude p-bromoacetanilide that was prepared above to a 100 mL round bottom flask. Add 10 mL of water and 10 mL of concentrated hydrochloric acid. Add two boiling chips and reflux the mixture at a gentle boil for 15- 20 minutes using your heating mantle. Since we are not using a flammable organic solvent, it is also safe in this step to use a low flame with your Bunsen burner, using your tripod and wire gauze. As you heat, swirl the flask to ensure mixing and to dissolve any remaining solid. All of the solid will dissolve and the solution will become orange in color.After 20 minutes of reflux at a gentle boil, remove the heat source and add 15 mL of water. Cool the flask to room temperature. Crystals of p-bromoaniline may separate. Prepare a solution containing 10 mL concentrated aqueous 40 mL water and 25 g ice in a 400 mL beaker. Pour the solution of p-bromoaniline from above into this solution. Stir the suspension and test the pH of thesolution by placing a drop on the test strip. It must be strongly basic (blue to litmus). Ifnot, add more concentrated ammonia.Collect the orange precipitate of p-boromoaniline by suction filtration using Buchner funnel and wash the solid filter cake with 10 mL of cold water. Recrystallize the rest of the material from water. Take about 0.5 gram of your product and recrystallize it from approximately 15mL of water. Use your 50 mL Erlenmeyer. Put ~ 0.5 g in the Erlenmeyer and add 10 mLof water. Use your stirring rod to disperse the compound as much as possible in the water to aid in dissolution. Heat the suspension to boiling. (It is safe to use your Bunsen burner here since we are using water). Once the water is boiling, stir the solution add more water 1-2 mL at a time until all of the material has dissolved. Once the solution becomes clear, remove it from the heat and allow it to cool slowly to room temperature and then immerse it in an ice bath. Collect the crystals by suction filtration using your Hirsh funnel. Leave the crystals to dry; then determine the melting point.
Record the weight and calculate the percent yield. Run a TLC of the crude and the recrystallized sample using dichloromethane as the solvent
Mechanism NH Br H3C O + H Br NHC H3C OH Br NH C H3C OH Br NH C H3C OH O H H Br NH C H3C OH O H H Br NH C H3C O H HSO4 OH Br NH2 + H3C O OH
3. Synthesis of Dibenzalacetone by Aldol Condensation
The reaction of an aldehyde with a ketone employing sodium hydroxide as the base is an example of a mixed aldol condensation reaction, the Claisen-Schmidt reaction. Dibenzalacetone is readily prepared by condensation of acetone with two equivalents of benzaldehyde. The aldehyde carbonyl is more reactive than that of the ketone and therefore reacts rapidly with the anion of the ketone to give a α-hydroxyketone, which easily undergoes base-catalyzed
dehydration. Depending on the relative quantities of the reactants, the reaction can give either mono- or dibenzalacetone. H O + H 3C C CH3 O O
Benzaldehyde Acetone Dibenzalacetone
1,5-diphenyl-1,4-pentadiene-3-one
Melting point 1100C,max320nm,max=34,300
In the present experiment, sufficient ethanol is present as solvent to readily dissolve the starting material, benzaldehyde, and also the intermediate, benzalacetone. The benzalacetone, once formed, can then easily react with another mole of benzaldehyde to give the product, dibenzalacetone.
Procedure:
In a 125 mL Erlenmeyer flask, dissolve 0.020 moles sodium hydroxide (pellets) in
4.0 mL of water. In a 50 ml Erlenmeyer flask weigh out accurately 0.0160 moles benzaldehye andweigh into the same flask 0.0080 moles acetone. Add 10 ml of 95% ethanol and pourthis mixture into the prepared solution of sodium hydroxide. Mix and swirl occasionallyfor fifteen minutes. A yellow, flocculent precipitate should form. Filter the solid product by vacuum using your spatula to transfer as much of the solid as possible. After no more liquid is coming through the filter paper, disconnect the filter flask from the vacuum line, wash the solid with 10 mL water and, after about one minute, reconnect to the vacuum. Repeat the wash in the same way using 2-3 mL chilled 95% ethanol. Allow air to be sucked around the crystals for about 2 minutes. Recrystallize the product from ethyl acetate using a water bath and hot plate to heat the solvent. Ethyl acetate is flammable. Use approximately 2.5 mL of solvent per gram of product. Add about 1/2 the expected amount of ethyl acetate, stir with your spatula and heat thesuspension to boiling. Add more ethyl acetate in 1 mL portions, reheating to boiling each time, until all solid material dissolves (solution becomes clear). Allow the solution to cool slowly to room temperature and
then cool in an ice bath. Collect the final product on the Buchner funnel by suction filtration. Record the weight of your compound and calculate the percent yield. Take the melting point.
Mechanism C O CH2 H3C H OH C O CH2 H3C C H O C O CH2 H3C C O H O H H C O CH H3C C O H H + O H H - H2O C O CH H2C C H H OH C O CH CH2 C H C H O C O HC H2C C H C H O O H H OH C O HC HC C H C H OH + H OH C O HC HC C H C H -H2O OH
Acetone enolizes in the strongly basic conditions. Note that benzaldehye cannot
enolize and so it must act as the electrophile. The nucleophilic alpha carbon then attacks the carbonyl of benzaldehyde. After proton transfer there is loss of water to give the a,b-unsaturated carbonyl that is stabilized by conjugation with the phenyl substituent. Notice how the π-electrons of the phenyl ring are delocalized all the way onto the carbonyl and onto the other carbonyl in the final dibenzylacetone product.
4. Preparation of Methyl Orange
Methyl orange is synthesized from sulfanilic acid and N,N-dimethylaniline using a diazonium coupling reaction. The first step is called “diazotization.” Sodium sulfanilate reacts with sodium nitrite in hydrochloric acid (i.e., nitroso cation) to form an unstable “diazonium salt.” The second step is the “diazonium coupling reaction.” The diazonium ion is used in situ, and reacts with N, N-dimethylaniline to form the acidic azo dye.
+ SO3H NH2 SO3 NH3 -+ Na 2CO3 2 2 SO3-+Na NH2 + CO2 + H2O
Sulfanilic Acid (zwitterion) Sodium Sulfanilate
SO3- +Na NH2 SO3- +Na N N+ HCl / NO2 -Cl -Sodium Sulfanilate Diazonium Chloride SO3- +Na N N+Cl -+ N CH3 H3C CH3COOH NaO3S N N N CH3 CH3 N,N-Dimethylaniline Methylorange
Methyl orange forms beautiful orange crystals and is used as an acid-base indicator The anion form is yellow and the acid form is red.
N N N CH3 CH3 S O O O X H N N N CH3 CH3 S O O HO
Yellow pH> 4.4 Red pH< 3.1 Inner salt f orm Mechanism
The first step is simply an acid base reaction. In order to dissolve the sulfanilic acid in the aqueous solution we add sodium carbonate.. When we add sodium nitrite and HCl, the nitroso ion is formed from sodium nitrite and this reacts with the amine to form a nitrosoammonium adduct that loses water under the acidic conditions after proton transfer. This gives the diazonium salt. Aromatic diazonium salts are stable at low temperature. The terminal nitrogen of the diazonium salt is very electron deficient. It can be attacked by good nucleophiles. We dissolve the dimethylaniline in acetic acid. This forms the dimethylaniline acetate salt. Neutralize this in situ and the dimethylaniline becomes a good nucleophile due to the activating effect of the dimethylamine substituent. Attack is in the para position due to hindrance at the ortho position by the bulky dimethylamine substituent.
NH2 S O O O Na O N O + HCl HO N O HCl O N O H H H2O + O N H NaO C ONa O HO S NH2 O O O N HCl HO S N O O N O H Cl H H H2O HO S N O O N O H H H Cl H2O HO S N O O N O H H HO S N O O N Cl H3C N CH3 H C O O H3C OH N H3C CH3 HO S N O O N N CH3 CH3 H HO S N O O N N CH3 CH3 Procedure:
In order to avoid any excess of a reagent that could decompose or cause decomposition and produce tar to contaminate our dye, you need to weigh the quantities of solid reagent very carefully to the accuracy of 0.05 g or better. In this experiment you will have to calculate for yourself some of the amounts of needed reagents. After you have calculated them, confirm your results with the instructor before proceeding.
Dissolve 0.010 mole of sulfanilic acid (anhydride) in about 50 ml of a solution of sodium carbonate containing 0.010 to 0.0125 moles of sodium carbonate in a 125 ml Erlenmeyer flask. The solution is prepared by the stockroom and its strength is indicated on the bottle, but you must calculate the exact amount needed. Warm the mixture slightly to speed up dissolution. Test one drop of the solution to make sure it is alkaline. If not, add a small amount (1-2 mL) sodium carbonate solution and check the pH again. Then add 0.010 moles sodium nitrite and cool to 25°C (room temperature). Put 40 g of ice in a 400 mL beaker and add enough hydrochloric acid of a 6M or a 12 M solution in order to provide a total of 0.030 mol HCl in the beaker. Add the
sulfanilate solution prepared above in a fine stream while stirring continuously. Keep this solution cold in the ice bath at all times. It now contains your diazonium salt, which will decompose if it becomes warm. It is only partially soluble in the aqueous solution and will precipitate as a bluish-greenish solid. Prepare a solution of N,N-dimethylaniline (0.010 mol) in 0.010 mol of acetic acid in a 25 ml Erlenmeyer flask.
Now add the dimethylaniline acetate solution slowly with constant stirring to the suspension of the diazonium salt. A dull, reddish-purple mass should appear. Now, very slowly add about 30 mL of 1.0 M sodium hydroxide solution with constant stirring. Add the NaOH a few mL at a time. The addition should take 10 -15 minutes. The actual coupling reaction does not occur until you add the NaOH. The reaction takes place best at about pH 7. Keep adding the NaOH until the solution becomes basic (blue to litmus). If the sodium hydroxide is added too quickly, then free dimethylaniline will separate out as an oily phase. This then leaves an equivalent amount of the diazonium salt unreacted. This excess salt decomposes to brown tar on warming to room temperature and contaminates the otherwise beautiful crystalline orange dye. At the end of the coupling reaction a yellow-orange or golden color should be observed. The product will now be recrystallized from the reaction mixture. Heat the reaction mixture to boiling using your tripod and Bunsen burner. Everything should dissolve and the solution should be clear (though it will be highly colored). If all the material does not dissolve when the solution is heated to boiling, add more water as needed. Then, allow it to cool slowly to room temperature to crystallize and then place the flask in an ice bath to get it as cold as possible. Remember: do not stir or shake the solution when it is cooling. Allow the crystals to form in an undisturbed flask. They will be much purer and larger if they form slowly in a motionless flask.
ORGANIC ESTIMATIONS
1. ESTIMATION OF ANILINE/PHENOL.
The reaction to be studied in this experiment is between bromate and bromide ions in the presence of acid and occurs according to the equation,
KBrO3 + 5KBr + 3H2SO4 3K2SO4 + 3H2O + 3Br2
In this reaction, the potassium and sulphate ions are “spectator” ions in that they are not themselves materially affected, so, in ionic terms the reaction may be summarised as,
5Br- + BrO3-+ 6H+
+ 3Br2 + 3H2O
The free bromine generated reacts with phenol /aniline forming tribromophenol/aniline.
OH + 3Br2 OH Br Br Br + 3HBr
Equivalent mass of phenol/aniline = = 15.5 (aniline)
A bromate-bromide mixture which easily liberate bromine in presence of an acid is used so as keep the concentration of bromine a constant.
Requirments:
1. Approximately N/10sodium thiosulphate. 2. Approximately N/10 brominating mixture.
