Phenols can react both at the hydroxyl group and at 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 to bromobenzene by the action of hydrogen bromide on it, while cyclohexanol, when heated with hydrogen bromide, is easily converted to bromocyclohexane:
Like alkoxides, phenoxides react with alkyl halides and other alkylating reagents to form mixed esters:
(23)
Phenetol
(24)
Anisol
Alkylation of phenols with halogenated hydrocarbons or dimethyl sulfate in an alkaline medium is a modification of the Williamson reaction. By the reaction of phenols alkylation with chloroacetic acid, such herbicides as 2,4-dichlorophenoxyacetic acid (2,4-D) are obtained.
(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 scheme:
(27)
1,2,4,5- Tetrachlorophenol 2,4,5-sodium trichlorophenoxide 2,4,5-trichlorophenol
When overheated at the stage of obtaining 2,4,5-trichlorophenol, instead of it, a very toxic 2,3,7,8-tetrachlorodibenzodioxin can be formed:
2,3,7,8-Tetrachlorodibenzodioxin
Phenols are weaker nucleophiles than alcohols. For this reason, unlike alcohols, they do not enter into the esterification reaction. To obtain esters of phenols, acid chlorides and 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 obtained by Friedel-Crafts alkylation
m-cresol with 2-propanol in the presence of sulfuric acid. Write this reaction.
2. Substitution in the ring
The oxy group of phenol very strongly activates the aromatic ring with respect to electrophilic substitution reactions. Oxonium ions are most likely formed as intermediates:
When carrying out the reaction of electrophilic substitution in the case of phenols, special measures must be taken in order to prevent poly-substitution and oxidation.
3. Nitration
Phenol nitrates much easier than benzene. When 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; it 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 a predominance O- isomer. This mixture is easily separated due to the fact that only O- the isomer is water vapor volatile. Great volatility O- nitrophenol is explained by the formation of an intramolecular hydrogen bond, while in the case of
P- nitrophenol, an intermolecular hydrogen bond occurs.
4. Sulfonation
Sulfonation of phenol is very easy and leads to the formation, depending on the temperature, mainly 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 acted upon with a slight excess of bromine water. What product and in what quantity is it formed?
6. Kolbe reaction
Carbon dioxide is added to sodium phenoxide by the Kolbe reaction, which is an electrophilic substitution reaction in which carbon dioxide is the electrophile
(33)
Phenol Sodium phenoxide Sodium salicylate Salicylic acid
Mechanism:
(M 5)
Aspirin is obtained by the action of acetic anhydride salicylic acid:
(34)
Acetylsalicylic acid
If both ortho-positions are occupied, then the substitution proceeds along 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
Condensation of phenol with acetone in an acidic medium gives 2,2-di (4-hydroxyphenyl) propane, which has received the industrial name 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. Kleisen rearrangement
Phenols undergo Friedel-Crafts alkylation reactions. For example, when phenol interacts 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 by the Kleisen rearrangement:
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Allylphenyl ether 2-Allylphenol
Reaction
(43)
It goes through the following mechanism:
(44)
Claisen rearrangement also occurs when allylvinyl 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.
Fluorescein is a bright chemical colorant that glows under ultraviolet light. This material is devoted to obtaining this particular chemical, which will certainly be informative and will interest lovers of chemistry and beautiful chemical experiments.
Let's start the experience by watching a video
So, what we need:
- phthalic anhydride;
- resorcinol;
- metal crucible;
- sand bath;
- gas-burner;
- anhydrous zinc chloride;
- hydrochloric acid.
First of all, we weigh 3 g into a metal crucible. phthalic anhydride.
Next, sprinkle 4.5 g to it. resorcinol.
We mix these substances and put them in a sand bath, after which we light a gas burner, with which we heat the mixture to the melting point, that is, about 180 degrees Celsius.
Heating is necessary to melt the phthalic anhydride / resorcinol mixture.
After melting the mixture, add two 2.1 gr. anhydrous zinc chloride. When this component is added, a condensation reaction occurs, during which two molecules of resorcinol and one molecule of phthalic anhydride combine to form a large molecule of fluorescein. This also releases two water molecules. Zinc chloride acts as a catalyst and takes over the resulting water.
After adding zinc chloride, the temperature needs to be raised to 220 degrees Celsius and the mixture is heated for another 15 minutes.
After 15 minutes of heating, remove the formed fluorescein from the heat and set it to cool so that it hardens.
After the fluorescein has hardened, it must be removed from the metal crucible. For this, you can use a chisel.
All of the fluorescein has been picked out of the metal crucible, so you can proceed to the next step, which is grinding into fine mortars to break up any large crystals.
After grinding, fluorescein must be washed out of residual zinc chloride. To do this, pour it into 10% hydrochloric acid and heat to a boil with stirring.
We filter the washed fluorescein through vacuum filtration.
An organic substance from the group of phenols, a simple diatomic phenol. Among chemists, the names resorcinol and 1,3-dihydroxybenzene are also used. The formula of resorcinol is similar to the formulas of hydroquinone and pyrocatechol, the difference is in the structure of the molecule; in how the OH groups are attached.
Properties
The substance is in the form of colorless needle crystals or a white crystalline powder with a pungent phenolic odor. Sometimes the powder can be pinkish or yellowish. If it is strongly colored, turns pink-orange or brown, it means that the reagent was stored incorrectly, and it has oxidized. Resorcinol is fire hazardous. It dissolves well in water, diethyl ether, ethyl alcohol, acetone. Can be dissolved in oils, glycerin. Almost insoluble in chloroform, carbon disulfide, benzene.
The reagent exhibits the chemical properties of phenols. Strong reducing agent, easily oxidized. Reacts with alkalis to form phenolate salts; with ammonia, halogens, with strong acids (for example, with nitric, sulfuric, picric, glacial acetic).
For the qualitative determination of resorcinol, the following reactions are used:
- with iron chloride - the solution turns into a deep purple, almost black;
- fusion with phthalic anhydride in the presence of a catalyst leads to the formation of a characteristically colored, fluorescent green substance - fluorescein. The fluorescein itself has a yellow-red color of the solution (the reaction distinguishes resorcinol from other phenols).
Dust of resorcinol and especially its vapors irritate the skin, respiratory organs, mucous membranes of the eyes. Inhalation of vapors and dust of the reagent causes coughing, nausea, heart palpitations, dizziness, therefore, it is necessary to work with resorcinol using respirators or masks, goggles, in overalls, in a ventilated room. If you suspect poisoning, you need to rinse the site of exposure to the reagent with plenty of water, take the victim to fresh air, call a doctor.
Store resorcinol in a sealed container, in dark, dry, cool rooms, strictly separate from flammable substances.
Application
Resorcinol is in demand in the chemical industry as a raw material 
for the production of artificial colors, fluorescein, resorcinol-formaldehyde resins, solvents, stabilizers, plasticizers and UV absorbers for plastics.
- In analytical chemistry, it is used in colorimetric studies. With its help, the content of zinc, lead, carbohydrates, furfural, lignin, etc. is determined.
- In the rubber industry.
- In the fur industry, as a dye for furs.
- It is widely used in medicine and pharmaceuticals. It is used as a disinfectant, cauterizing agent, wound healing agent, antihelmintic. It is part of solutions and ointments for the treatment of various, including fungal and purulent, skin diseases; acne, seborrhea, dermatitis, eczema, age spots.
- To obtain explosives.
GOUVPO PENZA STATE UNIVERSITY
Medical Institute
Specialty "Pharmacy"
Final interdisciplinary exam
Examination ticket number 11
1. Pharmaceutical enterprises and pharmacies receive medicinal plant raw materials harvested from the plant Arctostaphyllosuva-ursi (L.) Spreng., Family. Ericaceae.
During the analytical control of the quality criteria of raw materials, it was found that the content of active ingredients in the raw materials was 8%; humidity 10.5%; total ash 3.3%; ash insoluble in 10% hydrochloric acid solution 1%; browned and darkened leaves 2%; other parts of the plant (twigs, fruits) 4%, organic impurities 0.2%; mineral impurity 0.1%.
Analyze the results obtained and make a conclusion about the quality of raw materials and the possibility of their further use. Explain your decision.
Give a brief description of the plant and raw materials. What life form does the plant have, where does it grow (range, habitat), what are the features of collecting raw materials?
Indicate the chemical composition of raw materials and the formula of the main active ingredient. What class of substances does it belong to? Explain what physical and chemical properties of active ingredients are used in pharmacopoeial methods of qualitative and quantitative natural definition.
What pharmacological group does the raw material belong to? What drugs are obtained from raw materials?
2. When assessing the quality of substance "3", it was noted that in the samples of one series its appearance did not meet the requirements of the ND for the section "Description" - the samples were damp and dirty pink.
Give justification for the reasons for the change in its quality for this indicator in accordance with with properties and provide other tests characterizing the quality of this medicinal substances:
Give the Russian, Latin and rational name of the drug. Describe the physical and chemical properties (appearance, solubility, spectral and optical characteristics) and sludge use for quality assessment.
According to the chemical properties, suggest reactionsidentification and quantification methods. Writethose reaction equations.
Phenols
Acidic properties
Phenols exhibit significantly higher acidity than alcohols and water, but they are weaker than carbonic and carboxylic acids, and do not stain litmus.
The pKa values are as follows: phenol - 9.89, acetic acid - 4.76, carbonic acid - 6.12.
The more stable the anion, the stronger the acid.
Restorative properties
Phenols are easily oxidized even by atmospheric oxygen, thereforewhen storing them, the appearance of shades is possible(pink, yellow go, brown ).
O- Benzoquinone
Diatomic phenols oxidize faster than monohydric phenols... The oxidation rate also depends on the pH of the medium. In an alkaline environment, oxidation is faster. Due to the ease of oxidation of pharmaco peya introduces indicator: chromaticity . esorcinol is oxidized to form a mixture of products,but without m-quinones.Phenols dissolve well in aqueous solutions of alkalis withformation of phenolates however, this reaction cannot be used for quantitative determination due to hydrolysis of the resulting salt.
Phenols do not interact with hydrocarbons alkali metals, because they are weaker than carbonic acid and cannot displace it. Phenols and carboxylic acids are distinguished by the reaction of interaction with alkali metal bicarbonates.
A characteristic qualitative reaction to phenols is the formation of colored complexes [ Fe ( OR ) 6 ] 3 ~ with salts of three tape iron ... The color depends on the number of hydroxyl groups, their location, and the presence of other functional groups.
Coloring of complexes of phenol derivatives and iron (III) chloride
Halogenation
With an excess of bromine water, a yellow 2,4,4,6-tetra-bromocyclohexadien-2,5-one is formed:The halogenation of phenols proceeds most easily in an alkaline medium, but phenol is oxidized in a strongly alkaline medium. Resorcinol is brominated in an acidic medium, forming tribromresorcinol, which is soluble in water. If one of the positions is occupied (like thymol), a dibromo derivative is formed:
Halogenation reactions are also used for quantitativedetermination of phenols 
.
Nitrosation (Lieberman's nitrosoreaction)
An authenticity reaction such as an indophenol test is based on the ability of drugs to oxidize. As an oxidizing agent use bleach, chloramine, bromine water:
Reactions are blown in easily if O- and n-positions are not occupied.
The hydroxyl group associated with the aromatic nucleus in an alkaline solution is the strongest ortho- and para-orientant. In this regard, reactions are easy for phenols. halogenation, nitroasting, nitration, etc..
The nitroso group enhances hydrogen mobility in phenolichydroxyl, isomerization occurs. Emerging quinone oxime condenses with phenol:
Data on the color of the indophenols formed during Lieberman's nitrosoreaction are presented in table.
Table 37. Coloring of indophenols (obtained by nitrosation)
Nitration
Phenols are nitrated with nitric acid, diluted at room temperature, with educationO- and p-nitrophenol:
Adding solution sodium hydroxide enhances coloration due to the formation of a well-dissociated salt:
The reaction of the combination of phenols with a diazonium salt in an alkaline medium
Phenols readily enter into a substitution reaction with diazonium salts in an alkaline medium with the formation of azo dyes, which in this medium have a color from orange to cherry red:
This is a common reaction to phenols that do not have substituents in the ortho and para positions. The easier combination occurs in the para position due to the formation of a long chain of conjugated bonds.
Due to instability, the diazonium salt is prepared immediately before the reaction, using compounds with a primary aromatic amino group:
When an azo dye is formed, the pH of the medium should not be higher than 9.0-10.0, since in a strongly alkaline medium, the diazonium salt forms a diazohydrate that is not capable of azo coupling:
^ DiazohydrateOxidation and condensation reactions
The formation of arylmethane dyes occurs during the condensation of phenols with an aldehyde
Arylmethanedye(redcolors
For thymol, a condensation reaction with chloroform in an alkaline medium is proposed. The reaction product is colored red-violet:
For phenols with a free n-position, a condensation reaction with 2,6-dichloroquinonechlorimide is characteristic, while indophenol is formed:
The formation of an indophenol derivative is possible by nitration of thymol in the medium of acetic anhydride and concentrated sulfuric acid:
Reactions of condensation of phenols with lactones (phthalic anhydride) are often used. With phenol, the condensation product is called phenolphthalein and is used as an indicator that hasIn the local environment, raspberry color:
Thymol forms thymolphthalein - an indicator coloredin an alkaline environment in blue:
Resorcinol fusion in a porcelain crucible with an excess of phthalic anhydride in the presence of a few drops of concentratedH 2 S0 4 ... The resulting melt yellow-red after cooling, it is poured into a dilute alkali solution. Appears intensely green fluorescence of the fluorescein formed as a result of the reaction:
Purity analysis
V resorcinol determine the impuritypyrocatechol by reaction with ammonium with molybdate. In the presence of an impurity color appears, the intensity of which compare with the reference.
Another impurity in the preparation resorcinol -phenol . The phenol impurity is determined by smell, for this a preparation with a small amount water is heated in a water bath at a temperature of 40-50 ° C.
V thymole determine the impurityphenol by reaction with iron (III) chloride. By condition of the GF methodology concentration thymol due to its low solubility is 0.085%. Coloration complex of thymol with iron chloride at this concentration not res accepted, and if there isphenol impurities appears violet I am coloring. The admixture of phenol in the preparation is unacceptable.
quantitation
For quantitative determination of phenols is usedbromatometry: as straight(thymol), and reverse (phenol, resor-
qing, sinestrol) method. A preparation, an excess of a titrated solution of potassium bromate and potassium bromide is placed in a bottle with a ground stopper. Acidified with sulfuric acid:
The reaction takes place within 10-15 minutes; for this time, the bottle is left in a dark place. Then a solution of potassium iodide is added to the mixture and left for another 5 minutes:
Direct titration accepted by the GF for quantitative determination thymol. In direct titration, an excess drop of iodine changes the color of the indicators (methyl orange, methyl redleg). V back titration the released iodine is titrated with a solution sodium thiosulfate. Indicator - starch.
It should be remembered that the bromination process is influenced by the conditions of determination: the duration of the reaction, the concentration of the acid.
Molar mass equivalents, denoted asM(l/ z) followdying:
phenol-1/6,
resorcinol-1/6,
thymol-1/4,
In the opposite way, a control experiment must be carried out..
Resorcinol Resorcinum
m-Dioxybenzene
Resorcinol is a diatomic phenol and is a colorless or slightly pink or yellow needle crystals or crystalline powder. Sometimes the color of the crystals is almost brown. This is due to improper storage of resorcinol, which is very easily oxidized. Unlike other phenols, resorcinol dissolves very easily in water, alcohol, easily in ether. Let's dissolve in fatty oil and glycerin. It is difficult to dissolve in chloroform. When heated, it evaporates completely.
Resorcinol is an integral part of many resins and tannins, but it is obtained synthetically from benzene by sulfonation and alkaline melting. Benzene is treated with concentrated sulfuric acid to obtain benzenemetadisulfonic acid I.
Then the reaction mixture is treated with lime: under these conditions sulfo-acid forms a water-soluble calcium salt (II), excess sulfuric acid is removed in the form of calcium sulfate:
The resulting resorcinol is purified by distillation.
Resorcinol, like other phenols, is easily oxidized and is itself a reducing agent. It can recover silver from ammoniacal silver nitrate solution.
Resorcinol gives all the reactions characteristic of phenols, including with formalin-sulfuric acid (a red precipitate forms at the bottom of the test tube). A specific reaction to resorcinol, which distinguishes it from all other phenols, is the reaction of its fusion with phthalic anhydride in the presence of concentrated sulfuric acid to form fluorescein - a yellow-red solution with green fluorescence (pharmaco-peyne reaction).
The antiseptic effect of resorcinol is more pronounced than that of monohydric phenol. This is due to its stronger reducing properties.
The regenerative capacity of resorcinol is especially manifested in an alkaline environment.
It is used externally for skin diseases (eczema, fungal diseases, etc.) in the form of 2-5% water and alcohol solutions and 5-10-20% ointments.
Store in well-sealed orange glass jars (light stimulates oxidation).
