Phenolic acid derivatives. Reactions of the authenticity of esters of salicylic acid Phenyl salicylate application in medicine

quantitation

1. For the quantitative determination of all drugs, alkaline hydrolysis reactions can be used. To do this, take an excess of 0.5 M sodium hydroxide solution and hydrolyze the preparations in a boiling water bath with a reflux condenser.

Excess titrated alkali solution is titrated with 0.5 M hydrochloric acid solution.

1.1. GF X - for methyl salicylate and phenyl salicylate, the alkalimetric method of hydrolysis is used.

excess alkali and phenolates are titrated with bromocresol purple:

Indicator - phenolphthalein

1.2. GF X - for acetyl salicylic acid use the method of alkalimetry without preliminary hydrolysis - a variant of neutralization by the free OH-group

The drug is dissolved in neutralized ethanol cooled to 8-10 ° C and titrated with 0.1 M NaOH solution (indicator - phenolphthalein).

2. The bromatometric method is used for salicylic acid esters (after hydrolysis with NaOH)

-3HBr

3.SFM versus standard solution

UV spectroscopy for aspirin after alkaline hydrolysis with hydrogen peroxide. λ max \u003d 290 nm

4. In acelysine, glycine is determined by the acidimetric method of non-aqueous titration with perchloric acid.

Storage... In a well-sealed container, protected from light.

Application:

1. Aspirin is used internally as an antirheumatic, anti-inflammatory, analgesic and antipyretic agent, 0.25 - 0.5 g, 3 - 4 times a day.

2. Phenyl salicylate is used internally as an antiseptic for diseases of the intestines and urinary tract, 0.3-0.5 g. "Besalol", "Urobesal".

3. Methyl salicylate is prescribed as an antirheumatic, anti-inflammatory and analgesic agent for external use in the form of rubbing (sometimes mixed with chloroform and fatty oils).

Research recent years showed that aspirin in low doses has an antithrombotic effect, because inhibits platelet aggregation. It has been shown that it can be used in combination with certain amino acids for parenteral administration.

Salicylic acid amides

Osalmid (oxaphenamide) Osalmid Oxaphenamidum

p-oxyphenyl salicylamide

odorless white or whitish-purple powder. M.p. \u003d 175-178 ° C

Receiving:

phenyl salicylate n-aminophenol osalmide

Authenticity:

1. Carry out reactions for phenolic hydroxyl with FeCl 3 (alcohol solution), a red-violet color is formed.

2. The amide group is established by the products of hydrolysis in an acidic medium.

and) n-aminophenol is identified by reaction with resorcinol in an alkaline medium.

Aromatic acids are derivatives of aromatic hydrocarbons, in which one or more hydrogen atoms in the benzene nucleus are replaced by carboxyl groups. Benzoic acid and salicylic acid (phenolic acid) are of the greatest importance as medicinal substances and initial products of their synthesis:

The presence of an aromatic nucleus in the molecule enhances the acidic properties of the substance. The dissociation constant of benzoic acid has a slightly lower value (K \u003d 6.3 · 10 -5) than that of acetic acid (K \u003d 1.8 · 10 -5). Similar chemical properties also possesses salicylic acid, however, the presence of phenolic hydroxyl in its molecule increases the dissociation constant to 1.06 · 10 -3 and expands the number analytical reactionsthat can be used for qualitative about quantitative analysis. Benzoic and salicylic acids form salts when interacting with alkalis.

Aromatic acids, as well as inorganic or aliphatic, have an antiseptic effect. They can also irritate and cauterize tissues associated with the formation of albuminates. Pharmacological effect depends on the degree of acid dissociation.

Sodium salts of benzoic and salicylic acids, in contrast to the acids themselves, are readily soluble in water. In aqueous solutions, they behave like salts of strong bases and weak acids. pharmachologic effect salts and acids themselves are the same, however, due to their greater solubility, their irritating effect is lower.

Benzoic acid- Acidum benzoicum

Sodium benzoate-Natrii benzoicum

Properties. Benzoic acid - colorless needle crystals or white fine crystalline powder with so pl. 122-124.5 ° C. Sodium benzoate is a white fine crystalline powder, odorless or with a very faint odor, sweet-salty taste. The melting point is not determined.

Receiving .

1. Oxidation of toluene with potassium permanganate, manganese dioxide, potassium dichromate.

2. Vapor-phase catalytic process of oxidation of toluene by atmospheric oxygen to benzoic acid.

Authenticity ... Of the reactions of authenticity, specific for benzoic acid and its salts is the reaction of formation of a complex salt of a flesh color when it interacts with a solution of FeCl 3. To do this, benzoic acid is neutralized with an alkali indicator and then a few drops of Fe Cl 3 solution are added:

A necessary condition for this reaction is to obtain a neutral sodium salt of benzoic acid, since the precipitate of the complex salt will dissolve in an acidic medium; with an excess of alkali, a brown precipitate of iron (III) hydroxide will precipitate.

When benzoic acid is exposed to hydrogen peroxide in the presence of an iron (II) sulfate catalyst, it turns into salicylic acid, which can be detected by a violet color with a FeCl 3 solution:

One of the impurities in the preparation may be the product of incomplete chlorination of the initial synthesis substance (toluene), which is detected by the green color of the flame after the introduction of a grain of the preparation on a copper wire into the colorless flame of the burner - reactionBelyitein.

The quantitative content of the drug is determined by the method of neutralization in an alcoholic medium according to the phenolphthalein indicator:

Benzoic acid is used as a weak antiseptic in ointment bases; it also acts as an expectorant. Most often benzoic acid is used in the form of its sodium salt C 6 H 5 COONa. The introduction of sodium cation reduces the irritating effect of benzoic acid and at the same time somewhat reduces the antiseptic activity of the drug. Benzoic acid salts act as weak diuretics and, like benzoic acid itself, are used for food preservation.

Benzoic acid is volatile and should be stored in well-sealed bottles.

Sodium benzoate .

Receiving. Received by the reaction of neutralization of benzoic acid with soda or alkali:

The authenticity of the preparation is confirmed by the formation of a flesh-colored precipitate under the action of a FeCl 3 solution.

The dry residue after the calcination of sodium benzoate colors the burner flame in yellow (reaction to Na +). If this residue is dissolved in water, the reaction of the medium turns out to be alkaline to litmus (reaction to Na +).

A characteristic (but not official) reaction to sodium benzoate is a reaction with a 5% solution of copper sulfate - a turquoise precipitate forms. It is convenient to use this reaction in intra-pharmacy control as it is quickly performed and specific for a given drug.

When sodium benzoate is acted upon by mineral acid, a benzoic acid precipitate is formed, which is filtered, dried and confirmed by determining the melting point (122-124.5 °). This reaction is the basis for the quantitative determination of the drug: sodium benzoate is dissolved in water and, in the presence of an ester that extracts benzoic acid, titrated with acid using methyl orange indicator.

It is used internally as an expectorant and weak disinfectant. In addition, it is used to study the antitoxic function of the liver. The aminoacetic acid glycine-1 found in the liver reacts with benzoic acid to form hippuric acid, which is excreted in the urine. The state of the liver is judged by the amount of hippuric acid released.

Of the esters of benzoic acid, benzyl benzoate is currently used in medical practice.

Medical benzyl benzoate - Benzylii benzoas medicinalis.

Properties. A colorless oily liquid with a slightly aromatic odor. Pungent and pungent taste. Practically insoluble in water. Mixes up in any ratio with alcohol, ether and chloroform. Boiling point 316-317 ° C, mp. 18.5-21 ° C. FS 42-1944-89 regulatory document.

Receiving. The interaction of benzoyl chloride and benzyl alcohol in the presence of bases.

Authenticity.
1. IR spectrum.
2. UV Spectrum.

quantitation.

• Spectrophotometry.
• Gas-liquid chromatography.

Application. As an anti-scab agent, against lice. It is used in a number of cosmetics.

Release form: gel 20%, cream 25%, ointment 10%, emulsion.

PHENOLIC ACIDS. Salicylic acid. Acidum salicylicum.

Of the three possible isomers of phenolic acids, only salicylic or o-hydroxybenzoic acid exhibits the highest physiological activity.

Salicylic acid itself is currently of little use, but its derivatives are one of the most multi-tonnage drugs. Salicylic acid itself is acicular crystals or fine-crystalline powder. When heated, it can sublimate - this fact is used to purify salicylic acid in the production of acetylsalicylic acid. When heated above 160 ° C, dexarboxylates to form phenol.

Salicylic acid was first obtained by oxidation of phenol alcohol saligenin,which was obtained by hydrolysis of the glycoside salicin,contained in the bark of willow. From the Latin name for willow - Salix - the name "salicylic acid" comes from:

IN essential oil The plant Gaulteria procumbens contains salicylic acid methyl ester, which can also be saponified to produce salicylic acid.

However, natural sources of salicylic acid cannot meet the need for its preparations, and therefore the acid and its derivatives are obtained exclusively by synthetic means.

The method of obtaining salicylic acid from sodium phenolate is of the greatest interest and industrial importance. This method was first applied by Kolbe and improved by R. Schmidt. Dry sodium phenolate is exposed to carbon dioxide under a pressure of 4.5- 5 atm.at a temperature of 120-135 °. Under these conditions, CO 2 is incorporated into the phenolate molecule in the o-position with respect to the phenolic hydroxyl:

The resulting salicylic acid phenolate immediately undergoes intramolecular rearrangement, resulting in the sodium salt of salicylic acid, which, upon acidification, releases salicylic acid:

Salicylic acid exhibits both phenolic and acid properties. As phenol, it gives a reaction typical of phenol with ferric chloride solution. Salicylic acid, unlike phenols, can dissolve not only in alkalis, but also in carbonate solutions. When dissolved in carbonates, it gives a medium salt - sodium salicylate - used in medicine:

Disodium salt is formed in alkalis.

3. Melting point 158-161 ° C.

In the presence of an excess of bromine, decarboxylation occurs and tribromophenol is formed. This method is also used for quantitative determination.

Quantitation.

1. By the method of neutralization in an alcoholic solution with the indicator phenolphthalein (pharmacopoeial method).

2. Bromatometric method.

Excess bromine is determined iodometrically.

Application... Outwardly as an antiseptic and irritant.

Forms of release. Ointments 4%, salicylic acid, benzoic acid and petroleum jelly paste, salicylic-zinc paste, alcohol solutions 2%.

Storage... In tightly closed flasks, protected from light.

Sodium salicylate
Natrii salicylas

Getting the drug.

The authenticity of the drug.
1. By reaction with ferric chloride.
2. With Mark's reagent (a mixture of sulfuric acid with formalin) gives a red color.
3. Reaction of flame coloring to sodium cation.
4. The residue from incineration gives an alkaline reaction to litmus.
5. Formation of intense green coloration with a solution of copper sulfate. If a 5% CuSO 4 solution is added dropwise to an aqueous solution of sodium salicylate, an intense green color appears.

Quantitation.

1. Acidimetric direct titration method. A mixture of methyl orange and methylene blue is used as indicators.

2. Bromatometric method.

Application... Inside in powders and tablets as an analgesic and anti-inflammatory agent for rheumatism. Tablets 0.25 and 0.5 g, Tablets of sodium salicylate 0.3 and caffeine 0.05 g.

Salicylic acid esters .

METHYL SALICILATE - Methylii salicilas

In nature, it is found in the essential oil of the Gaulteria procumbens plant, but in industry it is obtained synthetically by heating salicylic acid with methyl alcohol in the presence of sulfuric acid. Methyl salicylate is a colorless liquid with a fragrant odor. Gives a characteristic reaction with ferric chloride for phenols. For a drug, it is determined as a characteristic index - a refractive index of 1.535-1.538. Inadmissible impurities are moisture and acid, so under these conditions the drug is hydrolyzed.

Quantitation. Carried out by the amount of alkali spent on the saponification of the ether. An excess of a titrated alkali solution is added to a sample of the preparation and heated, the alkali remaining after saponification is titrated with an acid.

It is used externally as an analgesic and anti-inflammatory agent, most often in the form of liniment with chloroform and fatty oils.

Phenyl salicylate - Phenylii salicylas

Phenyl salicylate (salol) is an ester of salicylic acid and phenol. It was first obtained by M.V. Nentsky in 1886. Considering the irritating effect of salicylic acid, he strove to find a drug that, while maintaining the antiseptic properties of phenol, did not possess the toxic properties of phenol and the irritating effect of acid. To this end, he blocked the carboxyl group in salicylic acid and obtained its ether with phenol. Studies have shown that salol, passing through the stomach, does not change, and in the alkaline environment of the intestine it is saponified with the formation of sodium salts of salicylic acid and phenol, which have curative action... Since the saponification occurs slowly, the salol saponification products enter the body gradually and do not accumulate in large quantities, which provides more long-term action drug. This principle of introducing potent substances into the body in the form of their esters entered the literature as the "salol principle" of M. V. Nentsky and was subsequently used for the synthesis of many medicinal preparations.

Properties... Small colorless crystals with low odor. Melting point 42-43 ° C.

Receiving. Phenyl salicylate is obtained synthetically. The most common and accepted method is the following:

Qualitative reactions. A free phenolic group is retained in the salol molecule; therefore, the reaction with a FeCl 3 solution gives a violet color. With Mark's reagent, like other phenols, the preparation produces a reddish coloration.

quantitation.

1. Saponification followed by titration of excess alkali with acid (pharmacopoeial method).
2. Bromatometric method.
3. Acidimetric sodium salicylate. A mixture of indicators is used for this. First, to a pink color with methyl red, the excess of alkali and phenolate is neutralized and then with methyl orange in the presence of ether.

Release form. Tablets 0.25 and 0.5 g, tablets with belladonna extract and basic bismuth nitrate.

Application. Antiseptic effect for the treatment of intestinal diseases.

Salicylic acid esters in the OH group. Acetylsalicylic acid - Acidum acetylsalicylicum.

o-Acetylsalicylic acid is a natural product and is found in the flowers of plants of the spirea species (spiraeaulmaria).This ester was introduced into the medical practice of treating acute articular rheumatism back in 1874, and as a synthetic medicinal substance it began to be produced on an industrial scale at the end of the last century under the name of aspirin (the prefix "a" meant that this medicinal substance is not extracted from spirea, but it is done chemically). Aspirin has been called the medicine of the 20th century. Currently, it is produced in the world over 100 thousand tons per year.

Its anti-inflammatory, antipyretic and analgesic properties are known. It was also found that it prevents the formation of blood clots, has a vasodilating effect and is even beginning to be used for the prevention and treatment of heart attacks and strokes. Believe that all the potential medicinal properties this substance has not yet been exhausted. At the same time, aspirin irritates the lining of the gastrointestinal tract, which can cause bleeding. Also possible allergic reactions... Aspirin in the body affects the synthesis of prostaglandins (controlling, in particular, the formation of blood clots) and the hormone histamine (dilating blood vessels and causing the influx of immune cells to the site of inflammation; in addition, it can interfere with inflammatory processes biosynthesis of pain substances).

Properties... Colorless crystals or white powder of slightly acidic taste. Let's slightly dissolve in water (1: 500), we will easily dissolve in alcohol.

Authenticity.

1. Saponification with caustic soda leads to the formation of sodium salicylate, which upon treatment with acid gives a precipitate of salicylic acid.

2. By violet coloration with ferric chloride after hydrolysis and cleavage of the acetyl fragment.

3. Salicylic acid gives a characteristic reaction of the formation of auric dye with Mark's reagent:

4. Melting point 133-136 ° C.

Salicylic acid is a specific impurity controlled according to the requirements of the Pharmacopoeia Monograph. The salicylic acid content should be no more than 0.05%. A method for analyzing the spectrophotometric complex formed by the interaction of ammonium iron alum with salicylic acid, colored blue.

quantitation .

1. Method of neutralization by the free carboxyl group (pharmacopoeial method). Titration is carried out in an alcoholic medium (to avoid hydrolysis of the acetyl group), phenolphthalein indicator.

2. Saponification followed by titration of excess alkali with acid for methyl orange. The equivalence factor is ½.

3. Bromatometric method.

4. HPLC in a buffered medium.

Release form. Tablets from 0.1 to 0.5 g. Enteric coated tablets are known. effervescent tablets... Used in compositional medicines in combination with caffeine, codeine and other substances.

Application- anti-inflammatory, antipyretic, antiplatelet agent.

Storage in sealed jars.

Works on the synthesis of other derivatives with a salicylate fragment are in progress. Thus, the preparation flufenizal was obtained (11), which is four times more active than aspirin in its anti-inflammatory effect (in rheumatoid arthritis) and is milder in relation to the gastric mucosa. It is obtained by fluorosulfonation of biphenyl derivative (7) to compound (8), in which SO 2 is then eliminated in the presence of triphenylphosphine rhodium fluoride. The formed fluoride (9) is hydrogenated to remove the benzyl protection, then a phenolate is obtained, which is carboxylated according to the Kolbe method to arylsalicylate (10). After acylation of compound (10), flufenisal (11) is obtained:

SALICYLIC ACID AMIDES

SALICYLAMIDE - Salicylamidum

Properties... White crystalline powder with so pl. 140-142 ° C.

Qualitative reactions.
1.In alkaline hydrolysis, sodium salicylate is formed and ammonia is released.
2. With bromine gives a dibromo derivative.

quantitation carried out on the released ammonia.

Release form... Tablets 0.25 and 0.5 g. Antipyretic agent.

OXAFENAMIDE Oxaphenamidum .

Properties... An odorless white or white with a lilac-gray tinge, so pl. 175-178 ° C.

Receiving... By fusing phenyl salicylate with p-aminophenol.

Phenols are distilled off. The remaining mixture is treated with isopropanol with hydrochloric acid. The crystals are filtered off and recrystallized from amyl alcohol.

Authenticity.

1. An alcoholic solution gives a red-violet color with ferric chloride.

2.Indophenol is formed with hydrochloric acid in the presence of resorcinol, which gives a red-violet coloration with caustic soda:

1.Kjeldahl method
2.HPLC.

Release form. Tablets 0.25 and 0.5 g.

Choleretic agent (cholecystitis, cholelithiasis).

Phenylpropionic acid derivatives

IBUPROFEN - Ibuprofenum

Colorless crystals, white powder, melting point 75-77 ° C, insoluble in water, soluble in alcohol.

Non-steroidal anti-inflammatory agent. The drug is relatively low-toxic, has a pronounced anti-inflammatory and analgesic activity, antipyretic effect, stimulates the formation of endogenous interferon. It is used to treat rheumatoid arthritis and other joint diseases, to lower the temperature in patients.

Below is the synthesis, which consists in the acetylation of isobutylbenzene according to Friedel-Crafts, the production of cyanohydrin by the reaction with sodium cyanide and the reduction of this cyanohydrin under the action of hydroiodic acid and phosphorus in p-isobutyl-α-methylphenylacetic acid - ibuprofen.

Authenticity .
1.UV spectrum.
2.IR spectrum
3. Sediment with ferric chloride.
4. The melting point of the substance is 75-77 ° C.

quantitation neutralization with an alcoholic solution of caustic soda with phenolphthalein in an alcoholic solution.

Release form. 0.2 g film-coated tablets. Compositional dosage forms with codeine (nurofen), etc.

Application... Non-steroidal anti-inflammatory agent. It has an analgesic effect.

Other non-steroidal anti-inflammatory drugs include:

DICLOFENAC SODIUM, Ortofen, Voltaren

Diclofenac sodium

Properties... White or grayish powder, soluble in water.

The drugs sodium diclofenac, mefenamic acid and indomethacin are similar in their anti-inflammatory and analgesic effects, the latter has slightly more significant effects in this regard, but the former is less toxic and has better tolerance. Sodium diclofenac and mefenamic acid penetrate well into the joint cavities in rheumatoid arthritis, it is used in acute rheumatism, arthrosis. It is used to relieve pain and diseases of the oral mucosa and periodontitis.

Receiving .

White or grayish powder, soluble in water. AUTHENTICITY:

1. precipitate with FeCl 3 - brown
2. UV spectrum
3. IR spectrum

QUANTITATIVE DEFINITION: HCl neutralization. APPLICATION:

Anti-inflammatory, antipyretic, with rheumatoid arthritis, 0.025, amp. 2.5% solution, Voltaren retard 0.1.

MEPHENAMIC ACID Acidum mephenaminicum

Crystalline powder of grayish-white color, odorless, bitter taste. Practically insoluble in water, poorly soluble in alcohol.

Receiving... The drug is obtained by condensation of o-chlorobenzoic acid with xylidine in the presence of copper powder as a catalyst.

Authenticity.
1.Melting point
2.UV spectrum
3.IR spectrum

Quantitation.
Conversion into soluble sodium salt and titration of excess sodium hydroxide.

Release form.Tablets 0.5 g, suspension. Application. Anti-inflammatory, pain reliever.

HALOPERIDOL Haloperidolum

Haloperidol is a 4-fluorobutyrophenone derivative. This is one of the newest groups of antipsychotics with a very strong effect.

Receiving ... The synthesis is carried out on two lines. First, according to Friedel-Crafts, fluorobenzene is acylated with γ-chloro-butyric acid chloride to form 4-fluoro-γ-chlorobutyrophenone (A). Then, according to scheme (B), a 1,3-oxazine derivative is obtained from 4-chloropropen-2-ylbenzene, which is then transformed in an acidic medium into 4- p-chlorophenyl-1,2,5,6-tetrahydropyridine. The latter, when treated with hydrogen bromide in acetic acid, turns into 4-hydroxy-4- p-chlorophenylpiperidine (B). And finally, with the interaction of intermediates (A) and (B), haloperidol is obtained.

White or yellowish powder, slightly soluble in water, soluble in alcohol.

AUTHENTICITY:
1.IR spectrum
2. UV spectrum
3. Boil with alkali and carry out the reaction for the chloride ion.

QUANTITATION:HPLC

APPLICATION: 0.0015 and 0.005 tab., 0.2% drop, 0.5% injection solution for stopping attacks of schizophrenic psychosis, with delirium tremens.

Gross formula

C 13 H 10 O 3

Pharmacological group of the substance Phenyl salicylate

Nosological classification (ICD-10)

CAS code

118-55-8

Characteristics of the substance Phenyl salicylate

White crystalline powder or small colorless crystals with a faint odor. Practically insoluble in water, soluble (1:10) in alcohol and caustic alkali solutions, readily soluble in chloroform, very easily in ether.

Pharmacology

pharmachologic effect - anti-inflammatory, antiseptic.

Being hydrolyzed in the alkaline contents of the intestine, it releases salicylic acid and phenol, denaturing protein molecules. Phenyl salicylate does not disintegrate in the acidic contents of the stomach, does not irritate it (as well as the oral cavity and esophagus) mucous membrane. Formed in small intestine phenol suppresses pathogenic intestinal microflora, and salicylic acid has anti-inflammatory and antipyretic effects, both compounds, partially excreted from the body by the kidneys, disinfect the urinary tract. Phenyl salicylate is significantly less active in comparison with modern antimicrobial drugs, but it is low-toxic, does not cause dysbiosis and other complications, and is often used in outpatient practice.

Application of the substance Phenyl salicylate

Bowel diseases (colitis, enterocolitis) and urinary tract (cystitis, pyelitis, pyelonephritis).

Phenylsalicylate Phenylii salicylas

Write latin name phenyl salicylate. Write down his graphical formula in a notebook.

Underline the functional grouping indicating that phenyl salicylate is an ester.

For the first time, phenyl salicylate was obtained by M.V. Nentsky (1886). He strove to find such a drug that, while maintaining the antiseptic properties of phenol, would not have the irritating effect of salicylic acid. To do this, he blocked the carboxyl group in salicylic acid and obtained its ether with phenol. Phenyl salicylate, passing through the stomach, does not change, and in the alkaline medium of the intestine it hydrolyzes with the formation of sodium salts of salicylic acid and phenol, which have a therapeutic effect. Since the hydrolysis is slow, the hydrolysis products of phenyl salicylate enter the body gradually and do not accumulate in large quantities, which ensures a more lasting effect of the drug. This principle of introducing into the body substances with irritating properties in the form of their esters entered the literature as the "salol principle" of M. V. Nentsky and was subsequently used for the synthesis of many drugs.

Phenyl salicylate is often used to coat pills when it is necessary for the pills to pass unchanged through the stomach and release drugs in the intestines.

Phenyl salicylate is obtained synthetically.

Write a synthesis scheme and name the intermediate products:

For drug samples, examine physical properties: appearance, smell. Check solubility in water, alcohol, ether, chloroform. Write your findings in a notebook. Check dissolving-

is there phenyl salicylate in sodium hydroxide? Give an explanation from a chemical point of view.

Phenyl salicylate with camphor, menthol, thymol forms intratectic mixtures.

The melting point of phenyl salicylate is 42-43 ° C.

Prove the authenticity of phenyl salicylate.

1. Conduct a reaction alcohol solution phenylsalicylate: with a solution of iron (III) chloride. What coloration is observed? Why is the reaction carried out in an alcoholic environment?

2. Carry out the reaction with concentrated sulfuric acid, followed by the addition of formalin. What coloration do you observe?

Explain the chemistry of the reaction; what role does sulfuric acid play here?

Why does phenol smell?

What does formalin react with to produce a pink coloration (aurine dye)?

Write the equations of chemical reactions.

3. Dissolve about 0.1 g of the preparation in 5 ml of sodium hydroxide, boil for 3 minutes, cool, add hydrochloric acid, a white precipitate falls out and the smell of phenol is felt.

Add the reaction equations:

Perform quantitative determination of phenyl salicylate (GPC).

Place an exact sample of the drug in a flask, add an exact volume of a titrated sodium hydroxide solution and heat under reflux in a boiling water bath. Explain what process is going on.

Then titrate the excess sodium hydroxide with hydrochloric acid until a stable yellow color according to the indicator (bromocresol purple). Write the reaction equations.

Indicate which method was used to quantify.

For what purpose is the drug used and why?

Phenyl salicylate Phenyl salicylate

Receiving.

Phenyl salicylate (salol) is an ester of salicylic acids and phenol. It was first obtained by MV Nentsky in 1886. Considering the irritating effect of salicylic acid, he sought to find a drug that, while retaining the antiseptic properties of phenol, did not possess the toxic properties of phenol and the irritating effect of acid. To this end, he blocked the carboxyl group in salicylic acid and obtained its ether with phenol. Studies have shown that phenyl salicylate, passing through the stomach, does not change, but in the alkaline environment of the intestine it is saponified with the formation of sodium salts of the salicylic cyst and phenol, which have a therapeutic effect. Since saponification occurs slowly, salol saponification products enter the body gradually and do not accumulate in large quantities, which ensures a longer action of the drug. This principle of introducing potent substances into the body in the form of their esters entered the literature as the "salol principle" of M. V. Nentsky and was subsequently used for the synthesis of many medicinal preparations.

Phenyl salicylate is obtained synthetically. The most common and accepted method is the following:

The resulting preparation is purified by recrystallization from alcohol

Description. Colorless crystals with low odor. They are insoluble in water. Soluble in alcohol, chloroform and very well in ether. Due to phenolic hydroxyl, it dissolves in alkalis. Gives eutectic mixtures with camphor, thymol, menthol. Has a very low melting point (42-43 0 C).

Authenticity reactions.

1.1. On phenolic hydroxyl. The reaction is carried out with a solution of FeCI 3 - violet color.

1.2. With Mark's reagent, like other phenols, the preparation gives a red coloration (auric dye)

1.3. Phenyl salicylate, when saponified, forms sodium salicylate and phenolate, which are identified by corresponding reactions.

If after saponification the mixture is acidified, free salicylic acid will be released in the form of characteristic needle-like crystals. The crystals are filtered off and the melting point is determined.

Purity test. Determine the absence of impurities of salicylic acid, sodium salicylate, phenol and the limiting content (according to standards) of impurities of chlorides, sulfates, heavy metals.

Quantitation.

1. Method of saponification. The method is based on the reaction of alkaline hydrolysis. The weighed portion is boiled in a flask with a reflux condenser with a certain volume of a standard NaOH solution for a certain time. After cooling the reaction mixture, the excess NaOH is titrated with a standard solution of HCI (bromocresol purple indicator)

NaOH + HCI → NaCI + H 2 O

2. Bromatometry method, back titration of saponification products:

3. Method of acidimetry using sodium salicylate formed after alkaline hydrolysis.

After saponification of the preparation with methyl red indicator, the excess of unbound alkali is neutralized with acid (to a clearly visible pink color). At the same time, sodium phenolate, which is hydrolyzed during the titration, is also neutralized. Sodium salicylate is then titrated with acid on methyl orange in the presence of ether. The amount of acid used to titrate the salicylate is converted to phenyl salicylate.

Application.It is used internally in powders and tablets for bowel diseases.

Storage. In well-sealed jars, preferably dark glass.

Control questions for consolidation:

1. What reagent can be used to distinguish phenyl salicylate from acetylsalicylic acid?

2. What is the general method for the quantitative determination of phenyl salicylate and acetylsalicylic acid?

3. What products are formed during acid hydrolysis of acetylsalicylic acid?

Mandatory:

1. Glushchenko N.N., Pletneva T.V., Popkov V.A. Pharmaceutical chemistry. M .: Academy, 2004.- 384 p. from. 221-228

2. State Pharmacopoeia Russian Federation/ Publishing House "Scientific Center for Examination of Funds medical use", 2008.-704s.: Ill.

Additional:

1. State Pharmacopoeia 11th ed., No. 1-M: Medicine, 1987 .-- 336 p.

2. State Pharmacopoeia 11th ed., No. 2-M: Medicine, 1989 .-- 400 p.

3. Belikov V. G. Pharmaceutical chemistry. - 3rd ed., M., MEDpress-inform-2009.616 s: ill.

Electronic resources:

1. Pharmaceutical library [Electronic resource].

URL: http: //pharmchemlib.ucoz.ru/load/farmacevticheskaja_biblioteka/farmacevticheskaja_tekhnologija/9

2. Pharmaceutical abstracts - Pharmaceutical educational portal [Electronic resource]. URL: http://pharm-eferatiki.ru/pharmtechnology/

3. Computer support of the lecture. Disk 1СD-RW.