Acetoacetic acid. Ways of using acetyl CoA

04.10.2020

Introduction

The objectives of the work are defined as follows:

1. To study the structure and properties, as well as structural features of acetoacetic ether (AUE) on the basis of electronic representations;

2. Consider the structural features and properties of other b - dicarbonyl compounds;

3. To study the keto-phenolic tautomerism of mono- and β-dicarbonyl compounds experimentally;

4. Study the dual reactivity using the example of AUE;

5. Study the syntheses based on AUE.

Work tasks:

1. Confirm the structure and properties of the AUE on the basis of the experiment;

2. To prove the connection of acetoacetic ether with other classes of organic compounds.

Literature review

Classification of dicarbonyl compounds

Table 1. Physical properties of some aldehyde and keto acids

Table 1 shows some of the physical properties of the first representatives of the homologous series of aldehyde and keto acids. In comparison with saturated monobasic carboxylic acids with the same molecular weight, oxo acids differ markedly in physical properties. Aldehyde and keto acids have the properties of both carboxylic acids and carbonyl compounds (aldehydes and ketones). In addition, they show a number of specific transformations associated with the presence of both functions and their mutual influence. Oxo acids exhibit stronger acidic properties than unsubstituted carboxylic acids. An increase in acidic properties is associated with a rather strong electron-withdrawing effect of the carbonyl group (- I), which leads to an enhancement of the mesomeric effect of the carboxyl group and an increase in the polarization of the O - H bond. induction effect.

Acetoacetic acid and its ester as C - H acid

The homologous series of β-ketonic acids begins with acetoacetic acid. It can be obtained by careful saponification of its esters or by adding water to diketene:

The ethyl ester of this acid plays an important role in organic synthesis:

It is used to produce various ketones and acids.

One of the synthetically most important reactions of esters under the action of bases is the autocondensation of ethyl acetate caused by sodium ethylate and leading to acetoacetic ester. This reaction is called Claisen condensation.

Ethyl acetate Acetoacetic ether

It is interesting in that it should be thermodynamically unfavorable. This assumption is justified in practice. Much effort has been made to find the conditions under which the yields of the condensation product were of practical importance.

Claisen condensation mechanism: the first stage is the formation of the ethyl acetate anion, which, being an extremely strong nucleophile, attacks the carbonyl carbon atom of the second ester molecule. Elimination of the ethylate ion further leads to the ester of β-acid, ethyl acetoacetate.

C 2 H 5 O - + H + - CH 2 CO 2 C 2 H 5 : - CH 2 CO 2 C 2 H 5 + C 2 H 5 OH

All these stages ultimately lead to an unfavorable equilibrium position and satisfactory yields of β-ketoesters are obtained only if the equilibrium can be shifted by removing one of the products. This can be achieved by distilling off the ethyl alcohol; it may, however, be difficult to carry this distillation to completion, and if the starting ester has a low boiling point, then this method is naturally not applicable.

On the other hand, a large excess of sodium ethylate can be used. This method is effective because ethanol is a weaker acid than the phenol of the ester, and the excess of ethylate shifts the equilibrium to the right due to the conversion of the β-ketoester to the phenol salt.

Obviously, the condensation product must be obtained from the phenol salt and isolated under conditions preventing the reverse decomposition reaction to the starting reagents. The best method turns out to be "freezing" the reaction mixture, for which it is poured into an excess of cold dilute acid.

A feature of acetoacetic ether is that in some reactions it behaves like a ketone, and in others like unsaturated alcohol. This unusual reactivity is due to the fact that acetoacetic ester is a mixture of two tautomeric forms.

Tautomerism is understood as a fairly quickly established equilibrium between isomers, which under normal conditions cannot be separated from each other. Particularly widespread in organic chemistry is the so-called prototropic tautomerism, in which tautomeric isomers differ from each other in the position of the H atom with a simultaneous redistribution of p - electrons. It includes triadic prototropic tautomerism.

Essentially, prototropic tautomerism corresponds to the position when the same base, due to the presence of several centers of basicity, corresponds to several conjugated acids.

A classic example of triad prototropic tautomerism is keto-enol tautomerism.

Acetoacetic ester usually exists as an equilibrium mixture of ketone and enol tautomers in a ratio of 92.5 to 7.5.

Keto form (92.5%) Enol form (7.5%)

The interconversion of the enol and ketone forms of acetoacetic ester is extremely sensitive to catalysis by bases and, to a lesser extent, acids.

However, in the event that contact with substances of an acidic or basic nature is completely excluded, the rate of mutual conversion is reduced so much that it becomes possible to separate the lower-boiling enol from the keto form by fractional distillation under reduced pressure. The tautomers separated in this way are stable for an arbitrarily long time when stored in quartz vessels and t0 \u003d 800C.

A number of methods have been developed to determine the content of enol and keto forms in an equilibrium mixture. Physical methods are usually the most accurate, since when carrying out chemical determinations there is always a danger of a shift in equilibrium under the influence of chemical action. To establish the composition of the allelotropic mixture in the case of acetoacetic ether, Knorr applied the refractometric method, he determined the refractive indices of pure desmotropic forms and the refractive index of their allelotropic mixture.

table 2

Based on the fact that in this case there is a direct relationship between the changes in refractive indices and changes in the composition of the mixture, Knorr calculated that acetoacetic ether contains 2% enol and 98% keto form. However, later it was shown that in this case the refractometric method turned out to be unsuitable due to the fact that the prism glass catalyzes the keto-enol transformation of acetoacetic ether. Subsequently, the refractive index of the thoroughly purified both desmotropic forms of acetoacetic ether was determined, taking into account their isomerization during the measurement. Based on these data, it was found that ordinary acetoacetic ester contains 7.4% enol.

The chemical determination of the content of the enol and keto forms can be applied only in the case when it is known that under the influence of the reagent there is no equilibrium shift during the experiment. As a consequence, the reaction with FeCl3 cannot be applied.

A chemical method for determining the composition of a keto-enol mixture was developed by Meyer. It is based on the fact that the enol form reacts almost instantly with bromine. The definition is made as follows. An excess of bromine is added to an alcoholic solution of acetoacetic ether at - 70 C; since the equilibrium disturbed during bromination is gradually restored again due to the transition of the keto form to enol, the excess of bromine is destroyed by adding b-naphthol. Since the formed bromoketo compound, the content of which corresponds to the content of enol in the allelotropic mixture, quantitatively reacts with HI with the release of free iodine, KI and sulfuric acid are added to the test solution; the released iodine is titrated. The whole process can be represented by the following diagram:

All work before titrating iodine should be done very quickly (~ 15 sec).

Under these conditions, hydrogen bromide, which usually promotes the enolization of acetoacetic ether, does not have a catalytic effect. In this way, it was found that the acetoacetic ester contains 7.7% of the enol and 92.3% of the keto form. Freshly distilled ether is much richer in the enol form, since the latter has a lower boiling point than the keto form, as a result of which the equilibrium position of the keto form of enol is partially shifted to the right.

In different solvents, the content of the enol form is different: the more polar the solvent, the higher the content of the ketone form:

Table 3. The content of the enol form in various solvents

Chemical properties of acetoacetic ether

enol dicarbonyl ether acetoacetic

1. Alkylation of acetoacetic ether.

Anions of esters of the acetoacetic type can be alkylated with alkyl halides. The ester is converted by the action of a strong base into the enolate anion, and the latter is further alkylated by the SN2 reaction with an alkyl halide. Usually C-alkylation predominates.

The acetoacetic ester can be hydrolyzed under acidic conditions to the corresponding acids, which readily decarboxylate when heated. Methylalkyl ketones are formed from alkylacetoacetic esters:

2. Acylation of acetoacetic ether.

Ester anions interact with acyl halides to form acylation products. These reactions are carried out with the greatest success if used to obtain the enol salt, and sodium hydride, since in this case the formation of an alcohol capable of reacting with an acyl halide does not occur.

3. Syntheses with AUE.

AUE is widely used in organic synthesis. It can be used to synthesize ketones, modify ether to form various derivatives. A number of additional possibilities for synthesis are provided by AUE enolates, which are capable of undergoing alkylation and acylation to form various substituted acetoacetic esters. Unlike sodium malonic ether, these reactions can proceed both at the hydroxyl oxygen atom and at the neighboring carbon atom. The SN2 reaction mechanism acts as an enolate ion as a nucleophile.

The direction of replacement is determined by several factors. The most important is the nature of the reagent R - X. The softer the acid is the leaving group "X", the easier the reaction will be at the soft reaction center - the carbon atom. This occurs during the alkylation of the enolate - anion with alkyl - iodides and - bromides.

The possibilities of using AUE in the synthesis of various products are expanding due to its ability to undergo cleavage in two directions. When heated with dilute solutions of alkalis or acids, the acetoacetic acid formed after hydrolysis decomposes with the formation of ketones. Treatment with concentrated alkali solutions leads to the formation of two acetic acid molecules from AUE (acid cleavage):

The mechanism of acid cleavage is a nucleophilic attack by a hydroxyl ion of a carbonyl carbon carrying a partial positive charge. After the addition of the hydroxide, the unstable product decomposes.

With diabetes, your body has difficulty transporting glucose, which is a type of sugar, from your blood to your cells. This leads to high blood glucose levels and insufficient cells in the blood, and remember that your cells need glucose as an energy source, so not allowing glucose to enter means cells are starving to death despite the presence of glucose right at the door. Basically, the body controls how much glucose is in the blood relative to how much it enters the cells through two hormones: insulin and glucagon. Insulin lowers blood glucose while glucagon increases blood glucose. Both of these hormones are produced by groups of cells in the pancreas called islets of Langerhans. Insulin is secreted by beta cells in the center of the islets, and glucagon is produced by alpha cells at the periphery of the islets. Insulin lowers blood glucose by binding to insulin receptors embedded in the cell membrane of various insulin-dependent tissues such as myocytes and adipose tissue. When activated, these insulin receptors cause the granules containing the glucose transporter inside the cage to fuse with the cell membrane, allowing glucose to be transported inside the cell. Glucagon acts in the opposite way, it raises blood glucose levels by causing the liver to produce new glucose molecules from other molecules and also break down glycogen. into glucose so that it can all be released into the blood. Diabetes mellitus is diagnosed when blood glucose levels become too high, and this occurs in 10% of the world's population. There are two types of diabetes - Type 1 and Type 2, and the main difference between the two is the main reason that causes blood glucose levels to rise. About 10% of people have type 1 diabetes and the remaining 90% of people with diabetes have type 2. Let's start with diabetes. type 1 diabetes, sometimes simply called type 1 diabetes. In this situation, the body does not produce enough insulin. The reason this happens is that in type 1 diabetes, there is a type 4 hypersensitivity reaction, or a cell-mediated immune response, when a person's own T cells attack the pancreas. As a quick overview, remember that the immune system has T cells that respond to a variety of antigens, usually small proteins, polysaccharides, or lipids, and that some of them are cells in our own body. There is no point in allowing T cells, which will attack your own cells, to spin around, and therefore there is a process of eliminating them called "self-tolerance". In type 1 diabetes, there is a genetic defect causing a loss of self-tolerance among T cells that specifically target beta cell antigens. Loss of self-tolerance means that these T cells are allowed to engage other immune cells and coordinate the attack on these beta cells. Loss of beta cells means less insulin, and a decrease in insulin means that glucose levels rise in the blood because glucose cannot enter the cells in the body. One very important group of genes associated with the regulation of the immune response is the human leukocyte antigen system, or the HLA system. And although this is called a system, it is essentially a group of genes in the 6th romosome that codes for most of the histocompatibility complexes, or MHC, which is a protein that is particularly important in helping the immune system recognize foreign molecules, as well as maintaining self-tolerance. MHC is like a serving tray that antigens present to the cells of the immune system. Interestingly, people with type 1 diabetes usually have specific HLA genes in common with each other, one called HLA-DR3 and the other HLA-DR4. But that's just a genetic clue, right? Because not everyone with HLA-DR3 and HLA-DR4 gets diabetes. In type 1 diabetes, beta cell destruction usually begins early in life, but sometimes up to 90% of beta cells are destroyed before symptoms appear. Four clinical symptoms of uncontrolled diabetes that all sound similar are polyphagia, glucosuria, polyuria, and polydipsia. Let's go through them in turn. Although there is a lot of glucose in the blood, it cannot enter the cell, which causes the cell to be energetically hungry, so in response, adipose tissue begins to break down fats, which is called lipolysis, and muscle tissue begins to break down proteins, both processes lead to weight loss in humans with uncontrolled diabetes. This catabolic state causes a person to feel hungry, also known as polyphagia. Phagia means to eat, and poly- means a lot. Now with high glucose levels, which means that when the glucose is filtered through the kidneys, some of it goes into the urine, called glucosuria. "Glucose-" refers to glucose, "-uria" to urine. Since glucose is osmotically active, water follows it, causing increased urinary output, or polyuria. "Poly-" again refers to "many," and "-uria" refers to urine. Finally, due to excess urination, people with uncontrolled diabetes become dehydrated and feel thirsty, or polydipsia. "Poly-" means "a lot," and "-dipsia" means thirst. Although people with diabetes are unable to produce their own insulin, they still respond to it, so treatment includes lifelong insulin therapy to regulate their blood glucose levels and essentially allow cells to use glucose. One rather serious complication with type 1 diabetes is called diabetic ketoacidosis, or DKA. To understand it, let's go back to the lipolysis process, where fats are broken down into free fatty acids. Once this happens, the liver converts fatty acids into ketone bodies such as acetoacetic acid and beta hydroxybutyric acid, acetoacetic acid is a keto acid because it has a keto group and a carboxyl group. This hydroxybutyric acid on the other side, although it remains alone from ketone bodies, technically it is not a keto acid since its ketone group was replaced by a carboxyl one. These ketone bodies are very important, as they can be used by cells as energy, but they also increase blood acidity, which is why it is called keto acid. lake If the blood becomes very "acidic" it can cause serious changes in the body. Patients can develop Kussmaul breathing, which is deep and labored breathing as the body tries to flush carbon dioxide out of the blood as a way to lower acidity. The cells also have a carrier that exchanges hydrogen ions (or protons-H +) for potassium. When the acidity of the blood rises, it is by definition loaded with protons that are sent into the cell, while potassium is sent out into the extracellular space. It should also be remembered that in addition to helping glucose to enter the cell, insulin stimulates sodium-potassium ATPase which helps potassium to return to the cell, and without insulin, more potassium remains in the extracellular fluid. Both of these mechanisms lead to an increase in potassium in the extracellular fluid, which quickly penetrates the bloodstream and causes hyperkalemia. Potassium is then excreted, so over time, although blood potassium levels remain high, the body's total potassium stores - which include potassium inside the cell - begin to decline. Patients will have a large anion gap, which reflects the large difference in unmeasured negative and positive ions in serum, largely due to the accumulation of keto acids. Diabetic ketoacidosis can even happen to people who have already been diagnosed with diabetes and who are already receiving insulin therapy. Under stress, like an infection, the body releases adrenaline, which in turn stimulates the release of glucagon. Too much glucagon can disrupt the delicate hormonal balance of glucagon and insulin towards an increase in blood sugar and can lead to the chain of events that we have described - an increase in blood glucose, loss of glucose in the urine, loss of water, dehydration, and at the same time a lack of alternative energy, the production of ketones bodies, or ketoacidosis. Interestingly, both ketone bodies decompose to acetone and are excreted as a gas when exhaled from the lungs, which gives a sweet-fruity smell to the person's breath. In general, this is the only "sweet" characteristic of this disease, which also causes nausea, vomiting, and, to a severe degree, mental changes and acute cerebral edema. Treatments for episodes of ketoacidosis include getting plenty of fluids to help with dehydration, insulin to help lower blood glucose levels, and replacing electrolytes such as potassium; all this helps to reverse ketoacidosis. Now let's switch over and talk about type 2 diabetes, in which the body produces insulin, but the tissues don't respond as well. The exact reason why cells do not "respond" is not fully known, in fact the body provides a normal amount of insulin, but cells do not move glucose transporters into their membranes in response to this, which, as you remember, is necessary for the transport of glucose into the cell, these cells therefore develop insulin resistance. Obesity, lack of exercise, hypertension are some of the risk factors for insulin resistance, but the exact mechanism of their development is still being investigated. For example, excess adipose tissue (or fat) is thought to induce the production of free fatty acids and so-called "adipokines", which are signaling molecules capable of causing inflammation, which appears to be associated with insulin resistance. In any case, many obese people do not have diabetes, so genetic factors probably play an important role here as well. We can also see this if we look at twin studies, where having a twin with type 2 diabetes increases the risk of developing type 2 diabetes, in the absence of other external factors. In type 2 diabetes, because tissues do not respond as well to normal insulin levels, the body begins to produce more insulin to achieve the same effect and remove glucose from the bloodstream. They do this through beta cell hyperplasia, an increase in beta cell numbers, and hypertrophy when they increase in size, all in order to produce more insulin. This works for a while, and by keeping insulin levels above normal, blood lucose levels can be kept at a normal level, called normoglycemia. Now, along with insulin, beta cells also secrete islet amyloid polypeptide, or amylin, and while beta cells secrete insulin, they also secrete an increased amount of amylin. Over time, amylin accumulates and collects in islets. This compensation of beta cells is not steady and over time these beta-processing cells become tired and inoperative and undergo hypotrophy (become smaller) and hypoplasia and die off. With the loss of beta cells and a decrease in blood insulin levels, blood glucose levels begin to rise and patients develop hyperglycemia, leading to similar clinical signs that I mentioned earlier as polyphagia, glucosuria, polyuria and polydipsia. But unlike type 1 diabetes, with type 2 diabetes, insulin circulates in the blood from beta cells that try to compensate for insulin resistance. This means that the insulin / glucagon balance is such that diabetic ketoacidosis usually does not develop. It has been said that a complication called hyperosmolar hyperglycemic state (or HHS) is more common in type 2 than type 1 diabetes - and this causes an increase in plasma osmolarity due to excessive dehydration and blood concentration. To understand this, remember that glucose is a polar molecule that cannot passively diffuse across the cell membrane, which means it behaves like a solute. And when the glucose level is very high in the blood (implying a hyperosmolar state), the won starts to leave the cells of the body and go into the vessels, leaving the cells relatively dry and shrinking instead of full and juicy. Blood vessels full of water lead to increased urination and dehydration of the entire body. And this is a very serious situation, since dehydration of body cells and especially of the brain can cause many symptoms including changes in mental status. With HHS, you can sometimes see mild ketonemia or acidosis, but not to the same extent as with DKA, and with DKA you can see some hyperosmolarity, so there is undoubtedly an overlap between the two symptoms. Besides type 1 and type 2 diabetes, there are also several other subtypes of diabetes mellitus. Gestational diabetes occurs when a pregnant woman has an increase in blood glucose during the third trimester. Although it is not completely known, the cause may be related to pregnancy hormones, which interfere with the action of insulin on insulin receptors. Also, sometimes patients can develop drug-induced diabetes when drugs have side effects that increase blood glucose levels. The mechanism in both cases is thought to be related to insulin resistance (as in type 2 diabetes) rather than an autoimmune destructive process (as in type 1 diabetes). The diagnosis of type 1 or type 2 diabetes is based on how much glucose floats in the blood and there are specific standards that the World Health Organization uses. Very often, a fasting glucose test is performed when a person does not eat or drink (except water, this is possible) for 8 hours and his blood glucose level is determined. A level from 110 milligrams per deciliter to 125 milligrams per deciliter indicates prediabetes, and 126 milligrams per deciliter or higher indicates diabetes. A non-fasting glucose test or random measurement can be performed at any time when 200 milligrams per deciliter or higher is a "red flag" for diabetes. Another test is called a glucose tolerance test, where a patient is given glucose and then a blood sample is taken at intervals to determine how well the glucose is released from the blood, the most important interval being 2 hours. A level from 140 milligrams per deciliter to 199 milligrams per deciliter denoting prediabetes while 200 or higher defines diabetes. Another point to remember is that when blood glucose rises, glucose can also bind to proteins that circulate around in the blood or cells, and this leads us to another type of test that can be done, and that is the HbA1c test, which determines the proportion hemoglobin in red blood cells, to which glucose is attached - called glycosylated hemoglobin. An HbA1c level of 6% to 6.4% indicates prediabetes, and 6.5% and above indicates diabetes. This proportion of glycosylated hemoglobin does not change every day, so it makes it clear if the glucose level has been increased over the past 2-3 months. Over time, high glucose levels can damage small blood vessels called the microvasculature. In arterioles, a process called hyaline arteriolosclerosis, when hyaline is deposited in the walls of arterioles, these deposits of proteins make the walls hard and stiff. In cypillaries, the basement membrane can thicken and make it difficult to transport oxygen from the capillaries to the tissue, causing hypoxia. One of the most significant effects is that diabetes increases the risk of damage to medium and large arteries and subsequent atherosclerosis, which can lead to heart attack or stroke, the leading causes of morbidity and mortality in patients with diabetes. In the eyes, diabetes can lead to retinopathy and signs of this can be seen when the fundus is enlarged, which reveals "cotton" patches or pinpoint hemorrhages - which can eventually lead to blindness. In the kidney, afferent and efferent arterioles, as well as the glomeruli themselves, can be damaged, leading to nephrotic syndrome, which slowly decreases the kidneys' ability to filter blood over time and may eventually add to dialysis. Diabetes can also affect nerve function, causing symptoms such as decreased sensitivity on the toes and hands, sometimes referred to as glove-and-sock distribution, as well as impairing the autonomic nervous system, which controls many body functions - everything from sweating before the transport of gases. Eventually, both poor blood supply and nerve damage can lead to ulcers (usually on the leg) that do not heal easily and can be quite severe and must be amputated. This is one of the complications of uncontrolled diabetes, which is why it is so important to prevent, diagnose, and control diabetes with a healthy lifestyle, drugs that reduce insulin resistance and even insulin therapy if beta cells are depleted. In fact, many people with diabetes can control their blood glucose levels very effectively and live full and active lives without any complications.

ACETOACETIC ACID

Ketone acid, CH 3 COCH 2 CO 2 H is obtained by soaping acetoacetic ether (see) with a weak alkali solution in the cold. After washing A., the acid is isolated with weak H 2 SO 4 and extracted with ether; after distillation of the ether dry A. acid is a thick liquid, miscible with water in all proportions; this is? strong acid; decomposes on heating into acetone and CO 2; with FeCl 2, like its esters, it gives a violet color. Its salts are fragile. Sodium and barium salts are sometimes found in urine. Nitrous acid decomposes A. acid into isonitrosoacetone and CO 2.

Brockhaus and Efron. Encyclopedia of Brockhaus and Efron. 2012

Acetoacetic acid

Acetoacetic-acid-3D-balls.png
Are common
Systematic name	3-oxobutanoic acid, propane-2-one-1-carboxylic acid.
Traditional names	acetoacetic, β-ketobutyric acid, diacetic acid, acetoacetate
Chem. formula	C 4 H 6 O 3
Physical properties
condition	colorless oily liquid
Molar mass	102.0886 ± 0.0045 g / mol
Thermal properties
T. float.	36.5 ° C
Chemical properties
pK a	3,77
Classification
Reg. CAS number	541-50-4
PubChem	96
SMILES
ChEBI	CHEBI: 15344
Data are based on standard conditions (25 ° C, 100 kPa) unless otherwise noted.

Structure

Physicochemical properties

Acetoacetic acid is a colorless mobile oily liquid, soluble in water in all respects, as well as in ethanol, diethyl ether. Unstable, even with weak heating (in aqueous solution) decomposes into acetone and carbon dioxide:

$\\ mathsf (CH_C (O) CH_2COOH \\ rightarrow CH_3C (O) CH_3 + CO_2 \\ uparrow)$ .

Its salts with heavy metals are even less strong, decomposing to form acetone even at ordinary temperatures.

Strong acid, pK a \u003d 3.77.

Acetoacetic acid is characterized by keto-enol tautomerism. As a result of the inductive effect of the keto group, acetoacetic acid is more "acidic" than its base, butyric acid.

Acetoacetic acid reacts with halogens (chlorine or bromine), which decompose it to the corresponding hydrogen halide, carbon dioxide and acetone halide (chloro- or bromoacetone):

Receiving

Acetoacetic acid is obtained by saponification (hydrolysis) of ethyl ester of acetoacetic acid, followed by interaction with dilute acids (sulfuric or nitric). Another method is based on the oxidation of butyric acid with hydrogen peroxide:

Acetoacetic acid can also be obtained using the Claisen condensation reaction (interaction of sodium with ethyl acetate), followed by hydrolysis of acetoacetic ester:

Application

A large amount of acetoacetic acid is used to produce acetoacetic ester (ethyl acetoacetate).

Participation in metabolism

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Notes

Literature

Hauptmann Z., Grefe Y., Remane H. Organic chemistry / Ed. prof. V.M. Potapov. Translated from German by Cand. chem. Sciences P.B. Terent'eva and Cand. chem. Sciences S.S. Churanova. - M .: "Chemistry", 1979. - 832 p.

Excerpt Characterizing Acetoacetic Acid

- Roll to the fifth gun! - shouted from one side.
- At once, more amicably, in a burlack style, - the cheerful shouts of those changing the gun were heard.
“Ay, I almost knocked off our master's hat,” the red-faced joker laughed at Pierre, showing his teeth. “Eh, awkward,” he added reproachfully to the cannonball that hit the man’s wheel and leg.
- Well, you, foxes! - the other laughed at the twisting militias who entered the battery for the wounded.
- Al does not porridge taste good? Ah, the crows, they stabbed! - they shouted at the militiamen, who had hesitated in front of a soldier with a torn off leg.
“That’s something, kid,” the men were teasing. - They don't like passion.
Pierre noticed how after each ball that hit, after each loss, the general animation flared up more and more.
As if from an advancing thundercloud, more and more often, brighter and brighter, a hidden, flaring fire flashed on the faces of all these people (as if to repulse the ongoing) lightning.
Pierre did not look ahead at the battlefield and was not interested in knowing what was going on there: he was completely absorbed in contemplation of this, more and more flaring fire, which in the same way (he felt) was kindling in his soul.
At ten o'clock the infantry soldiers, who were in front of the battery in the bushes and along the Kamenka River, retreated. From the battery it was seen how they ran back past it, carrying the wounded on their guns. Some general with his retinue entered the mound and, after talking with the colonel, looking angrily at Pierre, went downstairs again, ordering the infantry cover, who was standing behind the battery, to lie down to be less exposed to shots. Following this, in the ranks of the infantry, to the right of the battery, a drum was heard, shouts of command, and from the battery one could see how the ranks of the infantry moved forward.
Pierre looked over the shaft. One face especially caught his eye. It was an officer who, with a pale young face, walked backwards, carrying a lowered sword, and looked around uneasily.
The ranks of infantry soldiers disappeared into the smoke, their drawn-out screams and frequent firing of rifles were heard. A few minutes later, crowds of wounded and stretchers passed from there. The shells began to hit the battery even more often. Several people were lying uncleaned. The soldiers moved more busily and lively near the cannons. No one paid any attention to Pierre. Once or twice he was shouted at for being on the road. The senior officer, with a frown on his face, with big, quick steps, moved from one weapon to another. The young officer, blushing even more, commanded the soldiers even more diligently. The soldiers fired in, turned, loaded, and did their job with tense panache. They bounced on the move as if on springs.
A thundercloud moved, and the fire that Pierre had watched burned brightly in all faces. He stood beside the senior officer. A young officer ran up to the older one with his hand to the shako.
- I have the honor to report, Colonel, there are only eight charges, will you order to continue firing? - he asked.
- Buckshot! - Without answering, the senior officer shouted, looking over the shaft.
Suddenly something happened; the officer gasped and, curled up, sat down on the ground like a bird shot down on the fly. Everything became strange, vague and gloomy in Pierre's eyes.
One after another whistled cannonballs and fought against the parapet, the soldiers, the cannons. Pierre, who had not heard these sounds before, now only heard these sounds alone. On the side of the battery, on the right, with a shout of "hurray", the soldiers ran not forward, but backward, as it seemed to Pierre.
The cannonball hit the very edge of the rampart in front of which Pierre was standing, poured the earth, and a black ball flashed in his eyes, and at the same instant slapped into something. The militias, who had entered the battery, ran back.
- All buckshot! The officer shouted.
The non-commissioned officer ran up to the senior officer and in a frightened whisper (as a butler reports to the owner at dinner that there is no more required wine), he said that there were no more charges.
- Robbers, what are they doing! - shouted the officer, turning to Pierre. The senior officer's face was red and sweaty, and his frowning eyes glittered. - Run to the reserves, bring the boxes! - he shouted, angrily avoiding Pierre and turning to his soldier.

Acetoacetic acid (formula CH 3 · CO · CH 2 COOH) - organic keto acid; intermediate product of the exchange of fatty acids and amino acids. Acetoacetic acid is an organic compound from the group of β-keto acids.

Acetoacetic acid is characterized by keto-enol tautomerism. As a result of the inductive effect of the keto group, acetoacetic acid is more "acidic" than its base, butyric acid.

Acetoacetic acid reacts with halogens (chloro or bromo), which decompose it to the corresponding hydrogen halide, carbon dioxide and acetone (chloro- or bromoacetone):

Reactions of ketone cleavage of acetoacetic ester

35. Heterofunctional derivatives of the benzene series as drugs. Salicylic acid and its derivatives (acetylsalicylic acid, phenyl salicylate, methyl salicylate).

Among monofunctional benzene derivatives, a special place is occupied by a derivative with a carboxyl group - benzoic acid͵ used in medicine in the form of sodium salt (sodium benzoate) as an expectorant.

Free benzoic acid is found in some resins and balsams, as well as in cranberries, lingonberries, but is more often found in a bound form. As a heterofunctional compound p-aminophenol forms derivatives for each functional group separately and simultaneously for two functional groups. p-Aminophenol is poisonous. Of interest for medicine are its derivatives - paracetamol, phenacetin, which have analgesic (analgesic) and antipyretic effects.

Paracetamol is an N-acetyl derivative of p-aminophenol. Phenacetin is obtained by acetylation of a p-aminophenol ethyl ester called phenetidine.

Esters of aromatic amino acids have a common property - the ability to induce local anesthesia to some extent, ᴛ.ᴇ. loss of sensitivity. This property is especially pronounced in para-derivatives. In medicine, anesthesin and novocaine are used. Novocaine is used in the form of a salt (hydrochloride), which is associated with the extremely important increase in its solubility in water.

p-Aminobenzoic acid is a growth factor for microorganisms and is involved in the synthesis of folic acid, with a lack or absence of which microorganisms die. The name of the acid is associated with its release from spinach leaves (from Lat. Folium - leaf). Folic acid plays an important role in the metabolism of nucleic acids and proteins; in the human body is not synthesized.

Folic acid (vitamin B) includes three structural fragments - the pteridine nucleus, p-aminobenzoic and L-glutamic acids. Both functional groups of p-aminobenzoic acid are involved in the formation of bonds with two other components.

Salicylic acid belongs to the group of hydroxybenzoic acids. As o-hydroxybenzoic acid, it readily decarboxylates when heated to form phenol.

Salicylic acid is soluble in water, gives intense color with iron (III) chloride (qualitative detection of the phenolic hydroxyl group). It has an antispasmodic, antipyretic and antifungal effect, but as a strong acid (pKa 2.98) it irritates the digestive tract and is therefore only used externally. Inside, its derivatives are used - salts or ethers. Salicylic acid is capable of forming derivatives at any functional group. Sodium salicylate, esters of the COOH group (methyl salicylate, phenyl salicylate (salol)) and the OH group - acetylsalicylic acid (aspirin) are of practical importance. The listed derivatives (except for salol) have analgesic, antipyretic and anti-inflammatory effects. Due to its irritating effect, methyl salicylate is used externally as part of ointments. Salol is used as a disinfectant for intestinal diseases and is notable for the fact that it does not hydrolyze in the acidic environment of the stomach, but decomposes only in the intestine, therefore it is also used as a material for the protective membranes of some drugs that are not stable in an acidic environment stomach.

Of the other derivatives of salicylic acid, p-aminosalicylic acid (PAS) is of great importance as an anti-tuberculosis agent. PASK is an antagonist of p-aminobenzoic acid, which is extremely important for the normal functioning of microorganisms. Other isomers do not have this effect. m-Aminosalicylic acid is a highly toxic substance.

phenyl salicylate

An antiseptic, splitting in the alkaline contents of the intestine, releases salicylic acid and phenol. Salicylic acid has an antipyretic and anti-inflammatory effect, phenol is active against pathogenic intestinal microflora. It has some uro-antiseptic effect. Compared to modern antimicrobial drugs, phenyl salicylate is less active, but low toxic, does not irritate the gastric mucosa, does not cause other antibacterial therapy and antibacterial therapy.

methyl salicylate is a liquid that has anti-inflammatory, analgesic, irritating and distracting effects. The drug is prescribed for rheumatism, radiculitis, arthritis, exudative pleurisy.