Chemical experiment - we obtain fluorescein. Abstract: Reactions of phenols Preparation from aromatic sulfonic acids
Resorcinol
Qualitative reactions
1. Resorcinol solution from 1 drop of ferric chloride solution takes on different shades of blue to dark purple.
2. When 0.5 g of resorcinol is carefully heated with 0.1 g of tartaric acid and strong sulfuric acid, a dark carmine-red color appears.
3. When resorcinol is heated with phthalic anhydride, fluorescein is formed:
4. When heating several milliliters of a 2% solution of resorcinol in a caustic alkali solution in a water bath and adding a few drops of chloroform (or a solution of chloral hydrate), the mixture turns intense red (unlike hydroquinone and pyrocatechol), turning yellowish after acidification diluted acetic acid.
5. Bromine water produces a precipitate - see Quantitative determination.
quantitation
Bromometric determination is based on the fact that bromine in excess reacts with resorcinol to form tribromoresorcinol:
Excess bromine is determined iodometrically.
1 g of resorcinol is dissolved in water in a 100 ml volumetric flask and adjusted to the mark. 25 ml of this solution is poured into a 500 ml flask with a ground stopper, add 50 ml of bromate-bromide mixture (2.7833 g of potassium bromate and 50 g of potassium bromide in 1 liter of solution), 50 ml of water, 5 ml of hydrochloric acid ( specific gravity 1.15) and leave for one minute, after which another 20 ml of water and 1 g of potassium iodide are added. The liquid is left for 5 minutes and the released iodine is titrated with 0.1 N. sodium thiosulfate solution (indicator - starch solution). 1 ml 0.1 n. potassium bromate solution corresponds to 0.001835 g of resorcinol.
Goal of the work
The purpose of the work is to carry out oxidation and condensation reactions for phenol and its derivatives.
Theoretical part
Phenols are aromatic compounds that have hydroxyl groups directly attached to the aromatic ring. Based on the number of hydroxyls, monohydric, diatomic and polyatomic phenols are distinguished. The simplest of them, oxybenzene, is called phenol. Hydroxy derivatives of toluene (methylphenols) are called ortho-, meta- and para-cresols, and hydroxy derivatives of xylenes are called xylenols. Phenols of the naphthalene series are called naphthols. The simplest dihydric phenols are called: o - dioxybenzene - pyrocatechol, m - dioxybenzene - resorcinol, n-dioxybenzene - hydroquinone.
Many phenols are easily oxidized, often resulting in a complex mixture of products. Depending on the oxidizing agent and reaction conditions, different products can be obtained. Thus, during the vapor-phase oxidation (t = 540 0) of o - xylene, phthalic anhydride is obtained. A qualitative reaction to phenols is a test with a solution of ferric chloride, which produces a colored ion. Phenol gives a red-violet color, cresols give a blue color, and other phenols give a green color.
A condensation reaction is an intramolecular or intermolecular process of the formation of a new C-C bond, usually occurring with the participation of condensing reagents, the role of which can be very different: it has a catalytic effect, produces intermediate reactive products, or simply binds a split-off particle, shifting the equilibrium in the system.
The condensation reaction with the elimination of water is catalyzed by a variety of reagents: strong acids, strong alkalis (hydroxides, alcoholates, amides, alkali metal hydrides, ammonia, primary and secondary amines).
Work order
In this work, we test the possibility of the oxidation of phenols and the formation of phthaleins by the condensation reaction.
3.1 Oxidation of phenol and naphthol
Oxidation is carried out with a solution of potassium permanganate in the presence of a solution of sodium carbonate (soda).
3.1.1 equipment and reagents:
Test tubes;
Pipettes;
Phenol – aqueous solution;
Naphthol - aqueous solution;
Potassium permanganate (0.5% aqueous solution);
Sodium carbonate (5% aqueous solution);
3.1.2 Conducting the experiment:
a) place 1 ml of an aqueous solution of phenol or naphthol into a test tube;
b) add 1 ml of sodium carbonate solution (soda);
c) add potassium permanganate solution drop by drop while shaking the test tube. Observe the color change of the solution.
The oxidation of phenols usually occurs in different directions and leads to the formation of a complex mixture of substances. The easier oxidation of phenols, compared to aromatic hydrocarbons, is due to the influence of the hydroxyl group, which sharply increases the mobility of hydrogen atoms at other carbon atoms of the benzene poison.
3.2 Formation of phthaleins.
3.2.1 Preparation of phenolphthalein.
Phenolphthalein is formed by the condensation reaction of phenol with phthalic anhydride in the presence of concentrated sulfuric acid.
Phthalic anhydride condenses with phenols to give triphenylethane derivatives. Condensation is accompanied by the elimination of water due to the oxygen of one of the carbonyl groups of the anhydride and the mobile hydrogen atoms of the benzene nuclei of two phenol molecules. The introduction of dewatering agents such as concentrated sulfuric acid greatly facilitates this condensation.
Phenol forms phenolphthalein by the following reaction:
/ \ /
H H C
3.2.1.1 Equipment and reagents:
Test tubes;
Pipettes;
Electric stove;
Phthalic anhydride;
Sulfuric acid diluted 1:5;
3.2.1.2 Conducting the experiment:
b) add approximately twice the amount of phenol to the same test tube;
c) shake the contents of the test tube several times and carefully add 3-5 drops of concentrated sulfuric acid to it, continuing to shake;
d) heat the test tube on a hotplate until a dark red color appears;
e) cool the test tube and add 5 ml of water to it;
f) add an alkali solution drop by drop to the resulting solution and observe the color change;
g) after changing color, add a few drops of diluted sulfuric acid to the contents of the test tube until the original color returns or until discoloration occurs.
3.2.2 Preparation of fluorescein.
Fluorescein is formed by the condensation reaction of resorcinol with phthalic anhydride in the presence of concentrated sulfuric acid.
Diatomic phenols with hydroxyl groups in the meta position, entering condensation, release two water molecules, one due to the oxygen of one of the carbonyl groups of the anhydride and the mobile hydrogen atoms of the benzene nuclei of two phenol molecules. the second water molecule is released due to the hydroxyl groups of two phenol molecules to form a six-membered ring.
Resorcinol forms fluorescein by the following reaction:
OH HO OH HO OH
/ \ / \ /
H H C
3.2.1.1.Equipment and reagents:
Test tubes;
Pipettes;
Electric stove;
Phthalic anhydride;
Resorcinol;
Concentrated sulfuric acid;
Caustic sodium solution (5-10%);
3.2.2.1 Conducting the experiment:
a) weigh 0.1-0.3 g of phthalic anhydride and place in a test tube;
b) add approximately twice the amount of resorcinol to the same test tube and mix by shaking;
c) carefully add 3-5 drops of concentrated sulfuric acid to the contents of the test tube;
d) heat the mixture in a test tube until a dark red color appears. Heat on an electric stove;
e) cool the contents of the test tube and add 5 ml of water to it;
f) add 2-3 drops of the resulting solution into a clean test tube, add 1 ml of alkali solution and dilute with plenty of water. Observe the color change.
3.2.3 Aurin formation
Aurine is obtained by condensation of oxalic acid with phenol in the presence of sulfuric acid.
When heated in the presence of sulfuric acid, oxalic acid condenses with three phenol molecules, splitting off water and carbon monoxide to form aurin.
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H-O- -H H- -OH
-H. OH O =
| . C = O +3H 2 O+CO
H - C
3.2.3.1. Equipment and reagents:
Test tubes;
Pipettes;
Oxalic acid;
Concentrated sulfuric acid;
3.2.3.2 Conducting the experiment:
a) weigh 0.02-0.05 g of oxalic acid and approximately twice as much phenol;
b) place both reagents in a test tube and mix by shaking;
c) add 1-2 drops of concentrated sulfuric acid to the test tube;
d) carefully heat the test tube with the mixture until it begins to boil and an intense yellow color appears;
e) cool the test tube, add 3-4 ml of water and shake. Observe the color that appears;
f) add a few drops of alkali solution to the resulting solution and observe the color change;
3.3 Decomposition of urea (carbomic acid amide) when heated.
When heated above its melting point, urea decomposes, releasing ammonia. At a temperature of 150 0 -160 0 C, two molecules of urea split off one molecule of ammonia and give biureate, which is highly soluble in warm water:
H 2 N-OO-NH 2 +H-NH-OO-NH 2 H 2 N-CO-NH-CO-NH 2 +NH 3
Biureate is characterized by the formation of a bright red complex compound in an alkaline solution with copper salts, which has the following composition in a solution of sodium hydroxide:
(NH 2 CO NH CONH 2) 2 *2NaOH*Cu(OH) 2
3.3.1 Equipment and reagents:
Test tubes;
Electric stove;
Urea (carbamide);
Caustic sodium solution (5-7%);
Copper sulfur solution (1%).
3.3.2 Conducting the experiment:
a) weigh 0.2-0.3 g of urea and place in a dry test tube;
b) heat the test tube on an electric stove;
c) observe the changes taking place: melting, release of ammonia, solidification;
d) cool the test tube;
e) add 1-2 ml of warm water to a cooled test tube, shake and pour into another test tube;
f) add 3-4 drops of caustic soda solution to the resulting cloudy solution until transparent. Then add one drop of copper sulfuric acid solution and observe the color change (a beautiful purple color appears).
Related information.
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Fluorescein synthesis
I decided to conduct experiments with fluorescein, but there was no ready-made reagent at hand: I had to carry out a test synthesis. Phthalic anhydride and several grams of resorcinol were available. I took the methodology from the article as a basis.
For the test experiment, I did not calculate the required quantities of substances: I simply took 1 gram of phthalic anhydride, 1 gram of resorcinol, and mixed them. The mixture was placed in a 50 ml glass and moistened with approximately 0.5 ml of concentrated sulfuric acid.
The glass was secured above the switched on electric stove. The mixture melted and turned crimson. Later - reddish-brown. He regulated the heating by either removing it or placing a tile under the glass. In general, the mixture boiled gently for about 5 minutes. When the glass was removed from the stove, needles of phthalic anhydride formed in its upper part.
Prepared a solution of 0.5 g of sodium hydroxide in 50 ml of water. The mixture had to be poured from the glass into the alkali solution without allowing it to cool, otherwise it would harden. In the case of a test tube (see the cited article), this apparently was not difficult, but the glass had a larger surface - the mixture froze. We managed to pour only a few drops from the glass into the alkali solution, which froze at the bottom in the form of green balls. The solution turned yellowish-green with characteristic fluorescence.
It was difficult to get the rest of the frozen melt out of the glass. I decided: “If the mountain does not come to Mohammed, it is not a sin to go to the mountain.” Instead of trying to scoop out the product to transfer it to the lye, it is better to pour the lye into the beaker containing the frozen reaction mixture and wait for it to dissolve.
The result was a dark green liquid with sediment. He placed the glass on the switched off but still hot stove. The reaction mixture gradually left the walls, and the liquid turned brown.
I left it like that for the weekend. Then I was still worried that the glass had to be covered so that fluorescein in an alkaline environment would not be oxidized by air (I have not seen any indication of such a danger in the literature, but who knows...)
After the weekend I came to work and looked at my fluorescein (on Friday I left a glass of melt filled with an alkali solution on a cooling tile).
In the glass there was a yellow solution (sodium salt of fluorescein - uranine) and red powder - a precipitate of fluorescein. However, not all of the sediment was in powder form. A mass similar to caramel (undissolved melt) has stuck to the glass rod.
The contents of the glass were filtered: a yellow solution was formed, and a red precipitate settled on the filter.
When I looked at the procedure for obtaining fluorescein from resorcinol and phthalic anhydride, I was convinced that I had taken phthalic anhydride in excess (22.5 g of resorcinol requires 15 g of phthalic anhydride, but I took it at random: 1 g of resorcinol - 1 g of phthalic anhydride).
That is why not all the melt dissolved, the medium in the glass was clearly not alkaline, and most of the fluorescein was in the sediment (let me remind you: fluorescein is slightly soluble in water, and its sodium salt [uranine] is much better).
Transfer the stick with the mass stuck to it into a clean glass, add caustic soda granules and a little water. The melt gradually dissolved, forming a red-brown opaque solution. Later, I added alkali to the fluorescein that remained on the filter and also transferred it into solution. The solutions were combined.
(By and large, it was not necessary to filter out fluorescein: it was enough to drain the liquid from the sediment as much as possible, and add alkali to the resulting suspension. Of course, in addition to fluorescein, the resulting solution also contains alkali, sodium sulfate, sodium phthalate and, possibly, resorcinol residues, but for this is not of great importance for further experiments).
I added a drop of the brown solution to a three-liter jar of water. The drop gradually descended, forming vortex rings, threads and “clouds”. At first the drop was brown, then gradually became yellow-green with distinct fluorescence. Indescribable beauty. Later, a similar experiment was carried out in a five-liter jar.
So, let's start experimenting with fluorescein.
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Phenols can react at both the hydroxyl group and the benzene ring.
1. Reactions on the hydroxyl group
The carbon-oxygen bond in phenols is much stronger than in alcohols. For example, phenol cannot be converted into bromobenzene by the action of hydrogen bromide, while cyclohexanol, when heated with hydrogen bromide, is easily converted into bromocyclohexane:
Like alkoxides, phenoxides react with alkyl halides and other alkylating reagents to form mixed esters:
(23)
Phenetol
(24)
Anisole
Alkylation of phenols with halocarbons or dimethyl sulfate in an alkaline medium is a modification of the Williamson reaction. The alkylation reaction of phenols with chloroacetic acid produces herbicides such as 2,4-dichlorophenoxyacetic acid (2,4-D).
(25)
2,4-Dichlorophenoxyacetic acid (2,4-D)
and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T).
(26)
2,4,5-trichlorophenoxyacetic acid (2,4,5-T)
The starting 2,4,5-trichlorophenol is obtained according to the following scheme:
(27)
1,2,4,5-Tetrachlorophenol 2,4,5-trichlorophenoxide sodium 2,4,5-trichlorophenol
If overheated at the stage of producing 2,4,5-trichlorophenol, very toxic 2,3,7,8-tetrachlorodibenzodioxine can be formed instead:
2,3,7,8-Tetrachlorodibenzodioxin
Phenols are weaker nucleophiles than alcohols. For this reason, unlike alcohols, they do not enter into an esterification reaction. To obtain phenol esters, acid chlorides and acid anhydrides are used:
Phenylacetate
Diphenyl carbonate
Exercise 17. Thymol (3-hydroxy-4-isopropyltoluene) is found in thyme and is used as a medium-strength antiseptic in toothpastes and mouthwashes. It is prepared by Friedel–Crafts alkylation
m-cresol with 2-propanol in the presence of sulfuric acid. Write this reaction.
2. Substitution into a ring
The hydroxy group of phenol very strongly activates the aromatic ring with respect to electrophilic substitution reactions. Oxonium ions are most likely formed as intermediate compounds:
When carrying out electrophilic substitution reactions in the case of phenols, special measures must be taken to prevent polysubstitution and oxidation.
3. Nitration
Phenol nitrates much more easily than benzene. When it is exposed to concentrated nitric acid, 2,4,6-trinitrophenol (picric acid) is formed:
Picric acid
The presence of three nitro groups in the nucleus sharply increases the acidity of the phenolic group. Picric acid, unlike phenol, is already a fairly strong acid. The presence of three nitro groups makes picric acid explosive and is used to prepare melinite. To obtain mononitrophenols, it is necessary to use dilute nitric acid and carry out the reaction at low temperatures:
It turns out a mixture O- And P- nitrophenols with predominance O- isomer. This mixture separates easily due to the fact that only O- the isomer is volatile with water vapor. Great volatility O- nitrophenol is explained by the formation of an intramolecular hydrogen bond, while in the case
P- nitrophenol, an intermolecular hydrogen bond occurs.
4. Sulfonation
Sulfonation of phenol is very easy and leads to the formation, depending on temperature, predominantly ortho- or pair-phenolsulfonic acids:
5. Halogenation
The high reactivity of phenol leads to the fact that even when it is treated with bromine water, three hydrogen atoms are replaced:
(31)
To obtain monobromophenol, special measures must be taken.
(32)
P-Bromophenol
Exercise 18. 0.94 g of phenol is treated with a slight excess of bromine water. What product and in what quantity is formed?
6. Kolbe reaction
Carbon dioxide adds to sodium phenoxide by the Kolbe reaction, which is an electrophilic substitution reaction in which the electrophile is carbon dioxide
(33)
Phenol Sodium phenoxide Sodium salicylate Salicylic acid
Mechanism:
(M 5)
By reacting salicylic acid with acetic anhydride, aspirin is obtained:
(34)
Acetylsalicylic acid
If both ortho-positions are occupied, then the replacement takes place according to pair- position:
(35)
The reaction proceeds according to the following mechanism:
(M 6)
7. Condensation with carbonyl-containing compounds
When phenol is heated with formaldehyde in the presence of acid, phenol-formaldehyde resin is formed:
(36)
Phenol formaldehyde resin
By condensation of phenol with acetone in an acidic medium, 2,2-di(4-hydroxyphenyl)propane is obtained, industrially named bisphenol A:
Bisphenol A
2,2-di(4-hydroxyphenyl)propane
di(4-hydroxyphenyl)dimethylmethane
By treating bisphenol A with phosgene in pyridine, Lexan is obtained:
In the presence of sulfuric acid or zinc chloride, phenol condenses with phthalic anhydride to form phenolphthalein:
(39)
Phthalic anhydride Phenolphthalein
When phthalic anhydride is fused with resorcinol in the presence of zinc chloride, a similar reaction occurs and fluorescein is formed:
(40)
Resorcinol Fluorescein
Exercise 19. Draw a diagram of the condensation of phenol with formaldehyde. What practical significance does this reaction have?
8. Claisen rearrangement
Phenols undergo Friedel-Crafts alkylation reactions. For example, when phenol reacts with allyl bromide in the presence of aluminum chloride, 2-allylphenol is formed:
(41)
The same product is also formed when allylphenyl ether is heated as a result of an intramolecular reaction called Claisen rearrangement:
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Allylphenyl ether 2-Allylphenol
Reaction
(43)
It takes place according to the following mechanism:
(44)
The Claisen rearrangement also occurs when allyl vinyl ether or 3,3-dimethyl-1,5-hexadiene is heated:
(45)
Allyl vinyl ether 4-Pentenal
(46)
3,3-Dimethyl-2-Methyl-2,6-
1,5-hexadiene hexadiene
Other reactions of this type are also known, for example, the Diels-Alder reaction. They are called pericyclic reactions.
Receipt. Obtained from benzene.
Description. White or white with a slight yellowish tint crystalline powder with a weak characteristic odor. Under the influence of light and air it gradually turns pink.
Solubility. Very soluble in water and 95% alcohol, easily soluble in ether, very slightly soluble in chloroform, soluble in glycerin and fatty oil.
Authenticity.
1) When a solution of ferric chloride is added to a solution of the drug, a blue-violet color appears, turning from the addition of an ammonia solution to a brownish-yellow color.
2) When several crystals of the drug are fused in a porcelain cup with an excess of phthalic anhydride, a yellow-red melt is obtained. When the melt is dissolved in a sodium hydroxide solution, intense green fluorescence appears.
Melting temperature 109-112°.
quantitation.
Bromatometric method ( back titration option).
An exact weighed portion of the drug is placed in a volumetric flask, dissolved in water, an excess of 0.1 M KBrO 3, KBr, H 2 SO 4 is added, then a solution of potassium iodide is added to the mixture, the mixture is shaken vigorously and left for 10 minutes in a dark place. After this, chloroform is added and the released iodine is titrated with 0.1 M sodium thiosulfate solution until colorless.
KBrO 3 + 5KBr + 3H 2 SO 4 → 3Br 2 + 3K 2 SO 4 + 3H 2 O
Br 2 + 2KJ = J 2 + 2KBr
J 2 + 2Na 2 S 2 O 3 = 2NaJ + Na 2 S 4 O 6
UC = 1/6, back titration formula
Storage. In well-sealed orange glass jars.
Application. An antiseptic for skin diseases, eczema, externally in ointments, pastes or solutions, rarely used internally as a gastrointestinal disinfectant.
Resorcinol incompatible with thymol, menthol, aspirin, camphor (forms dampening mixtures).
Easily decomposes (in an alkaline environment) - oxidizes, reduces mercury preparations to metallic.
Cm. Educational and methodological manual on intrapharmacy control: eye drops - resorcinol solution 1%.
Aromatic acids
Aromatic acids are organic compounds that have the functional group –COOH and a benzene ring as a radical.
The simplest representative is benzoic acid.
The properties of aromatic acids are determined by:
1. Properties of the benzene ring, which is characterized by:
1.1. Reactions of substitution of hydrogen in the nucleus with halogen, NO 2 -, SO 3 2- - groups.
2. Properties – COOH group.
2.1. Form salts with alkali, heavy metals, alkalis, alkali metal carbonates.
2.2. Form anhydrides, acid halides, amides.
2.3. Form esters in the presence of concentrated sulfuric acid.
3. The reaction of aromatic acids is determined by indicators (acidic).
Free aromatic acids are used only externally, because dissociating into ions, they split off the H + ion, which has an irritating effect, even cauterizing. In addition, when it enters the blood, it changes the structure of blood cells, so only salts and esters of aromatic acids are prescribed internally.
