The carboxyl group in the benzoic acid molecule has electron-withdrawing inductive and mesomeric effects with respect to the aromatic ring (an analogy with the structure of benzaldehyde - Ch. 10.8.2). The electron density on the ring is reduced, especially in about- and P- provisions. The oxygen atom is also involved in conjugation OH-groups, in connection with which the entire molecule has a planar structure.
10.9.3. Physical and chemical properties
Aromatic carboxylic acids are white crystalline substances, some of them have a pleasant smell.
The most important properties of the carboxylic acids themselves (aromatic as well as aliphatic) and, in some cases, their derivatives such as amides, are their acid-base properties. At the same time, the main properties are insignificant and have no practical significance.
As well as for aliphatic analogs, reactions in the acyl group are characteristic for aromatic acids and their derivatives, leading to the preparation of some derivatives from others.
Another important property of these compounds is the reactions at the benzene ring, which is typical for all aromatic derivatives.
10.9.3.1. Acid properties
The acidic properties of aliphatic carboxylic acids have been discussed previously (chapter 6.4.4.1). For aromatic carboxylic acids, acidity is also associated with the possibility of abstraction of a hydrogen cation from the carboxyl group. At the same time, arene monocarboxylic acids are weak OH-acids. Benzoic acid is only slightly stronger than acetic ( RK a for benzoic is 4.17 versus 4.76 for acetic). This can best be explained by the possibility of a more complete delocalization of the negative charge of the anion of the acid residue with the participation of the -electron system of the benzene ring.
Therefore, just as in the cases with arenesulfonic acids (chapter 10.3.3.4) and phenols (chapter 10.5.3.1), electron-withdrawing substituents will increase the acidic properties, and electron-donating substituents, on the contrary, will decrease.
However, for some substituents in ortho- the position of the benzene ring in relation to the carboxyl group, the effect on the acidic properties of arenecarboxylic acids is not limited to inductive and mesomeric effects (and the spatial effect too). This so-called ortho effect, manifested in the interaction of carboxyl and located in it in about-position R-donor group due to intramolecular hydrogen bonds. An example of manifestation ortho-effect is the interaction of functional groups in the molecule of salicylic acid, which increases its acidity compared to benzoic ( RK a = 3.00) by increasing the polarity IS HE-bonds in the carboxyl group and stabilization of the resulting anion:
salicylic acid
This is also characteristic of anthranilic ( about-aminobenzoic) acid, for phthalic ( about-benzenedicarboxylic acid) and similar in structure about-substituted benzoic acids.
In general, arenedicarboxylic and arenepolycarboxylic acids are stronger than monocarboxylic acids (the acceptor effect of the second carboxyl group affects).
Amides and imides of some acids also have significant acidic properties. For example, phthalimide is a typical (though weak) NH-acid ( RK a = 8.3):
It dissolves in aqueous alkalis (salt formation followed by hydrolysis). Therefore, to obtain stable salts, they are synthesized in an anhydrous medium.
Phthalimide salts (such as potassium phthalimide) have found use in the preparation of pure primary amines ( Gabriel synthesis*):
The first stage here is the interaction of a haloalkane with potassium phthalimide, which is a nucleophile, a typical reaction S N in the haloalkanes series. This is followed by hydrolysis of the formed N- alkylphthalimide, which is usually carried out in a hydrochloric acid medium.
10.9.3.2. Reactions in the acyl group
Previously, using the example of aliphatic analogs (Chapter 6.4.4.2), nucleophilic substitution reactions in the carboxyl group of carboxylic acids and in the acyl groups of derivatives of these acids were considered. In this case, other acyl derivatives are formed from some acyl derivatives.
Acid catalysis is also possible.
The reaction rate depends on spatial factors, the magnitude of the charge on the carbonyl carbon atom, and the nature of the leaving group (its basicity). Thus, the reactivity of aromatic carboxylic acids and their derivatives decreases in the same order as their aliphatic counterparts:
Arenecarboxylic acids are also characterized by decarboxylation reactions, starting with a nucleophilic attack on the carbonyl carbon atom (chapter 6.4.4.4).
10.9.3.3. Electrophilic substitution
As follows from the structure of benzoic acid, the carboxyl group has an electron-withdrawing effect on the benzene ring, and therefore reduces the electron density on the ring and directs the entering electrophile mainly to meta- position. This can be shown by the boundary formulas for the electron density distribution in the initial benzoic acid molecule:
From S E-reactions for arenecarboxylic acids (and their acyl derivatives) are characterized by nitration, sulfonation and halogenation reactions. For example:
ACETYLSALICYLIC (2-(ACETYLOXY)-BENZOIC) ACID- a white crystalline substance, slightly soluble in water, soluble in alcohol, in alkali solutions. This substance is obtained by the interaction of salicylic acid with acetic anhydride:
Acetylsalicylic acid has been widely used for over 100 years as a drug - antipyretic, analgesic and anti-inflammatory. There are more than 50 names - trademarks of drugs, the main active ingredient of which is this substance. This unusual drug can be called a champion among drugs. Acetylsalicylic acid is a long-liver in the world of drugs, officially celebrated its centenary in 1999, and is still the most popular drug in the world. The annual consumption of medicines containing acetylsalicylic acid exceeds 40 billion tablets.
Another feature of acetylsalicylic acid is the first synthetic medicinal substance. From time immemorial, man has used medicinal plants, then he learned to isolate medicinal substances in their pure form from plant extracts, but acetylsalicylic acid became the first medicine, a complete analogue of which does not exist in nature.
In nature, there is a similar substance - salicylic acid. This compound is found in willow bark and is healing properties have been known since antiquity. A decoction of willow bark as an antipyretic, analgesic and anti-inflammatory agent was recommended by Hippocrates. In 1828, the German chemist Buechner isolated a substance from willow bark, which he named salicin (from the Latin name for willow - Salix). A little later, pure salicylic acid was obtained from salicin, and it was proved that it has medicinal properties. Salicin, isolated from willow bark, a waste from basket production, has been used as a medicinal product, however, it was produced in very small quantities and was expensive. In 1860, the German chemist A. Kolbe developed a method for the synthesis of salicylic acid by the interaction of sodium phenolate with carbon dioxide, and soon a plant for the production of this substance appeared in Germany:
Both salicin and the cheaper synthetic salicylic acid have been used in medical practice, but are widely used as a drug for internal use did not receive salicylic acid. Due to its high acidity, it causes severe irritation of the mucous membranes of the mouth, throat, stomach, and its salts - salicylates - have such a taste that most patients feel sick from them.
A new drug with the same therapeutic properties, but less pronounced side effects as salicylic acid, was discovered and patented by the German company Bayer. By official version the father of chemist Felix Hoffman, who worked in the firm, suffered from rheumatism, and the loving son set out to obtain a substance that would alleviate the suffering of his rheumatic father, but would have a more pleasant taste than salicylates and would not cause stomach pain. In 1893, he discovered the desired properties in acetylsalicylic acid, first obtained from salicylic acid forty years earlier, but did not find application. Hoffman developed a method for obtaining pure acetylsalicylic acid, and after testing the drug on animals (by the way, they were also carried out for the first time in history) in 1899, Bayer patented trademark aspirin is the name by which this drug is best known. It is believed that the name of the medicine was given in honor of St. Aspirinus, the patron saint of all headache sufferers, although there is a more prosaic explanation. Salicylic acid was often called spirsaeure at that time, because it is also found in the meadowsweet (spiraea) marsh plant. And the brand name is simply an abbreviation for the then accepted name of acetylsalicylic acid acetylspirsaeure. By the way, salicylic acid also found its place in medicine, its solution - salicylic alcohol treats skin inflammatory processes and is part of many cosmetic lotions.
Acetylsalicylic acid lowers the temperature, reduces local inflammation, anesthetizes. It also thins the blood and is therefore used when there is a risk of blood clots. It has been proven that long-term use of a small dose of acetylsalicylic acid by people prone to diseases of the cardiovascular system significantly reduces the risk of stroke and myocardial infarction. At the same time, the drug is completely devoid of the terrible lack of many painkillers - addiction does not develop to it. It seemed like the perfect drug. Some people are so accustomed to this drug that they take it with or without reason - at the slightest pain or just "just in case".
But in no case should we forget that drugs should not be abused. Like any drug, acetylsalicylic acid is not safe. An overdose can lead to poisoning, manifested by nausea, vomiting, stomach pain, dizziness, and in severe cases, toxic inflammation of the liver and kidneys, damage to the central nervous system(disorder of coordination of movements, clouding of consciousness, convulsions) and hemorrhages.
If a person takes several medications at the same time, you need to be especially careful. Some drugs are incompatible with each other, and because of this, poisoning can occur. Acetylsalicylic acid increases the toxic effects of sulfonamides, enhances the effect of painkillers and anti-inflammatory drugs such as amidopyrine, butadione, analgin.
This medicine has side effects. Just like salicylic acid, although to a much lesser extent, it leads to irritation of the mucous membranes of the stomach. To avoid negative effects on the gastrointestinal tract, it is recommended to take this medicine after meals with plenty of fluids. The irritating effect of acetylsalicylic acid enhances wine alcohol.
In many ways, the irritating effect of aspirin is due to its poor solubility. If you swallow a tablet, it is slowly absorbed, an undissolved particle of the substance may “stick” to the mucous membrane for some time, causing irritation. To reduce this effect, simply crush an aspirin tablet into powder and drink it with water, sometimes alkaline mineral water is recommended for this purpose, or buy soluble forms of aspirin - effervescent tablets. However, it should be borne in mind that these measures do not reduce the risk of gastrointestinal bleeding due to the effect of the drug on the synthesis of "protective" prostaglandins in the gastric mucosa. Therefore, it is better not to abuse acetylsalicylic acid, especially for people with gastritis or stomach ulcers.
Sometimes the effect of reducing blood clotting can be undesirable or even dangerous. In particular, preparations containing acetylsalicylic acid are not recommended during the week before surgery, as it increases the risk of unwanted bleeding. Pregnant women and young children should not take acetylsalicylic acid preparations unless absolutely necessary.
Despite the fact that acetylsalicylic acid has been known for so long and is very widely used as a drug, an explanation of the mechanism of its action on the body appeared only in the 1970s. The British scientist J.Vayne for his work on the study of the physiological action of acetylsalicylic acid in 1982 received Nobel Prize in Physiology or Medicine and a knighthood by Queen Elizabeth II. Wayne discovered that acetylsalicylic acid blocks the synthesis of certain hormone-like substances in the body - prostaglandins, which are responsible for the regulation of many body functions, in particular, it inhibits the synthesis of prostaglandins that cause inflammation. Side effects of acetylsalicylic acid are explained by a slowdown in the synthesis of other prostaglandins responsible for blood clotting and regulation of the formation of hydrochloric acid in the stomach.
Further research showed that not all properties of this substance are associated with blocking the synthesis of prostaglandins. The mechanism of action of acetylsalicylic acid is complex and not fully understood, and its properties are still the subject of research by many scientific teams. In 2003 alone, about 4000 scientific articles were published on the intricacies of the physiological action of this substance. On the one hand, scientists are finding new uses for an old drug - for example, recent studies have revealed the mechanism of the effect of acetylsalicylic acid on lowering blood sugar levels, which is important for diabetics. On the other hand, based on research, new medications acetylsalicylic acid, the side effects of which are minimized. Obviously, acetylsalicylic acid will provide work for more than one generation of scientists - physiologists and pharmacists.
Materials on the Internet: http://www.remedium.ru
http://www.brandpro.ru/world/histories/h02.htm
http://www.inventors.ru/index.asp?mode=4212
http://www.roche.ru/press_analytic_medpreparat_apr.shtml
Ekaterina Mendeleeva