What is the peculiarity of the structure of aromatic structures. Aromatic hydrocarbons (arenes): classification, nomenclature and isomerism, physical properties

aromatic hydrocarbons- compounds of carbon and hydrogen, in the molecule of which there is a benzene ring. The most important representatives of aromatic hydrocarbons are benzene and its homologues - the products of substitution of one or more hydrogen atoms in the benzene molecule for hydrocarbon residues.

The structure of the benzene molecule

The first aromatic compound, benzene, was discovered in 1825 by M. Faraday. Its molecular formula was established - C 6 H 6. If we compare its composition with the composition of the saturated hydrocarbon containing the same number of carbon atoms - hexane (C 6 H 14), then we can see that benzene contains eight fewer hydrogen atoms. As is known, the appearance of multiple bonds and cycles leads to a decrease in the number of hydrogen atoms in a hydrocarbon molecule. In 1865, F. Kekule proposed its structural formula as cyclohexantriene-1,3,5.

Thus, the molecule corresponding to the Kekule formula contains double bonds, therefore, benzene must have an unsaturated character, i.e., it is easy to enter into addition reactions: hydrogenation, bromination, hydration, etc.

However, numerous experimental data have shown that benzene enters into addition reactions only under harsh conditions(at high temperatures and lighting), resistant to oxidation. The most characteristic of it are the substitution reactions, therefore, benzene is closer in character to saturated hydrocarbons.

Trying to explain these inconsistencies, many scientists have proposed various versions of the structure of benzene. The structure of the benzene molecule was finally confirmed by the reaction of its formation from acetylene. In fact, the carbon-carbon bonds in benzene are equivalent, and their properties are not similar to those of either single or double bonds.

Currently, benzene is denoted either by the Kekule formula, or by a hexagon in which a circle is depicted.

So what is the peculiarity of the structure of benzene?

Based on these studies and calculations, it was concluded that all six carbon atoms are in the state of sp 2 hybridization and lie in the same plane. The unhybridized p-orbitals of carbon atoms that make up double bonds (Kekule's formula) are perpendicular to the plane of the ring and parallel to each other.

They overlap with each other, forming a single π-system. Thus, the system of alternating double bonds depicted in the Kekule formula is a cyclic system of conjugated, overlapping π-bonds. This system consists of two toroidal (donut-like) regions of electron density lying on both sides of the benzene ring. Thus, it is more logical to depict benzene as a regular hexagon with a circle in the center (π-system) than as cyclohexantriene-1,3,5.

The American scientist L. Pauling proposed to represent benzene in the form of two boundary structures that differ in the distribution of electron density and constantly transform into each other:

The measured bond lengths confirm this assumption. It was found that all C-C bonds in benzene have the same length (0.139 nm). They are somewhat shorter than single C-C bonds (0.154 nm) and longer than double ones (0.132 nm).

There are also compounds whose molecules contain several cyclic structures, for example:

Isomerism and nomenclature of aromatic hydrocarbons

For benzene homologues the isomerism of the position of several substituents is characteristic. The simplest homologue of benzene is toluene(methylbenzene) - does not have such isomers; the following homologue is presented as four isomers:

The basis of the name of an aromatic hydrocarbon with small substituents is the word benzene. Atoms in an aromatic ring are numbered starting from senior deputy to junior:

If the substituents are the same, then numbering is carried out according to the shortest path: for example, substance:

called 1,3-dimethylbenzene, not 1,5-dimethylbenzene.

According to the old nomenclature, positions 2 and 6 are called ortho positions, 4 - para-, 3 and 5 - meta positions.

Physical properties of aromatic hydrocarbons

Benzene and its simplest homologues under normal conditions - highly toxic liquids with a characteristic unpleasant odour. They are poorly soluble in water, but well - in organic solvents.

Chemical properties of aromatic hydrocarbons

substitution reactions. Aromatic hydrocarbons enter into substitution reactions.

1. Bromination. When reacting with bromine in the presence of a catalyst, iron (III) bromide, one of the hydrogen atoms in the benzene ring can be replaced by a bromine atom:

2. Nitration of benzene and its homologues. When an aromatic hydrocarbon interacts with nitric acid in the presence of sulfuric acid (a mixture of sulfuric and nitric acids is called a nitrating mixture), a hydrogen atom is replaced by a nitro group - NO 2:

Reduction of nitrobenzene is obtained aniline- a substance that is used to obtain aniline dyes:

This reaction is named after the Russian chemist Zinin.

Addition reactions. Aromatic compounds can also enter into addition reactions to the benzene ring. In this case, cyclohexane and its derivatives are formed.

1. Hydrogenation. The catalytic hydrogenation of benzene proceeds at a higher temperature than the hydrogenation of alkenes:

2. Chlorination. The reaction proceeds under illumination with ultraviolet light and is a free radical:

Chemical properties of aromatic hydrocarbons - compendium

Benzene homologues

The composition of their molecules corresponds to the formula CnH2n-6. The closest homologues of benzene are:

All benzene homologues following toluene have isomers. Isomerism can be associated both with the number and structure of the substituent (1, 2), and with the position of the substituent in the benzene ring (2, 3, 4). Compounds of the general formula C 8 H 10 :

According to the old nomenclature used to indicate the relative position of two identical or different substituents in the benzene ring, prefixes are used ortho-(abbreviated as o-) - substituents are located at neighboring carbon atoms, meta-(m-) - through one carbon atom and pair-(p-) - substituents against each other.

The first members of the homologous series of benzene are liquids with a specific odor. They are lighter than water. They are good solvents. Benzene homologues enter into substitution reactions:

bromination:

nitration:

Toluene is oxidized by permanganate when heated:

Reference material for passing the test:

periodic table

Solubility table

Detailed lecture program
comments on the second part of the course

The detailed lecture program and comments on the second part of the general course of lectures in organic chemistry (PPL) are based on the Program of the general course of organic chemistry, developed at the Department of Organic Chemistry, Faculty of Chemistry, Moscow State University. PPL reveal the filling of the second part of the general course of lectures with factual material on the theory and practice of organic chemistry. PPL is intended primarily for 3rd year students who want to prepare well and fairly quickly for exams and colloquia and understand how much knowledge a student should have in order to get an excellent mark on the exam. The PPLs are prepared in such a way that the mandatory material of the program is printed in normal type, the optional material is in italics, although it should be recognized that such a division is sometimes rather arbitrary.

One of the goals of this manual is to help students correctly and accurately compose a lecture summary, structure the material, make the right accents in the recording, separate the required material from the secondary when working independently with a summary or textbook. It should be noted that despite the widest distribution of modern teaching methods and the availability of a variety of educational material in textbooks and on the Internet, only independent persistent, if not hard work on taking notes (lectures, textbooks, other materials), work at seminars, independent writing of the most important equations and mechanisms, and independent solution of synthetic problems can lead to success in the study of organic chemistry (and other subjects as well). The authors believe that listening to a course of lectures creates the basis for the study of organic chemistry and covers all topics submitted for the exam. However, the lectures listened to, as well as the textbooks read, remain passive knowledge until the material is consolidated at seminars, colloquiums, when writing tests, tests and analyzing errors. There are no equations of chemical reactions and mechanisms of the most important processes in PPL. This material is available in lectures and textbooks. Each student must acquire some knowledge on their own: write the most important reactions, mechanisms, and preferably more than once (independent work with lecture notes, with a textbook, colloquium). Only what is acquired through independent painstaking work is remembered for a long time and becomes active knowledge. What is easy to get is easily lost or forgotten, and this is true not only in relation to the course of organic chemistry.

In addition to program materials, this development contains a number of auxiliary materials that were demonstrated at lectures and which, according to the authors, are necessary for a better understanding of organic chemistry. These auxiliary materials (numbers, tables, etc.), even if they are printed in a normal font, are most often not intended for literal memorization, but are needed to assess trends in the properties or reactivity of organic compounds. Since the auxiliary materials shown at lectures, figures, tables can be difficult to fully and accurately write down in a summary, the placement of these materials in this development is intended to help course participants fill in the gaps in notes and notes, and focus on lectures not on shorthand numbers and tables, but on perception and understanding of the material discussed by the lecturer.

AROMATICITY.

1. Aliphatic (from Greek αλιφατικό - oil, fat) and aromatic (αρωματικόσ - incense) compounds (XIX century).

2. Discovery of benzene (Faraday, 1825). The structure of benzene (Kekule, 1865). o-, m-, p-isomers, ortho-xylene.

3. Other formulas proposed for benzene (Ladenburg, Dewar, Thiele, and others). Benzene isomers (prisman, bicyclohexa-2,5-diene, benzvalene, fulvene).

4. Hückel molecular orbital method. Independent consideration of σ- and π-bonds (i.e. formed by sp 2 and p-orbitals). Molecular orbitals of benzene (three orbitals bonding: one orbital has no nodes, two orbitals have one nodal plane each, they are all occupied, there are only 6 electrons on them; three orbitals are loosening. Two of them have 2 nodal planes, the highest energy loosening orbital has three nodal planes, antibonding orbitals are not occupied.

The concept of the Frost circle for benzene, cyclobutadiene and cyclooctatetraene.

Hückel's rule. FLAT, MONOCYCLIC, CONJUCATED hydrocarbons will be aromatic if the cycle contains (4n+2) π - electrons.

antiaromatic compounds. non-aromatic compounds. Cyclooctatetraene.

5. Description of benzene by the "valence schemes" method, resonance theory (Pauling), mesomerism, use of limiting structures.

6. Canceled. Metanoannulled. aromatic ions. condensed hydrocarbons. Heterocycles.

A few comments on the stability of annullens.

-annulled - not flat, can not be aromatic.

1,6-methano-- annulled- flat, (except for the bridge, of course!), it is aromatic.

Annulene is a non-aromatic polyene, stable below -70°C.

-annulled not flat cycles if there are no 2 bridges. Therefore, they are not aromatic.

Annulenes are ordinary polyenes.

-annulled- flat, aromatic. Know the peculiarity of its PMR spectrum!

7. Detailed consideration AROMATIC CRITERIA.

Aromaticity criteria – quantum mechanical – number of p-electrons 4n+2(Hückel's rule), see comments below. Energy (increasing thermodynamic stability due to electron delocalization, the so-called delocalization energy - ED). ED in benzene: (6a + 8β) - (6a + 6β) (for cyclohexatriene) \u003d 2β \u003d 36 kcal / mol or 1.56 eV - this is EER (Empirical Resonance Energy). There are several more ways to calculate the resonance energy: vertical resonance energy (aka ED according to Hückel, measured in units of the integral β, for benzene it is 0.333), still happens (at 5++) ERD (i.e. Dewar resonance energy, per 1 electron, 0.145 eV for benzene), still happens (at 5+++) Hess-Schaad ER, for benzene: 0.065 eV, then the same as EDNOE in the textbook Reutov, Kurts, Butin. It also happens (at 5++++) FER (topological ER). Still "there is much in the world, friend Horatio, which our wise men never dreamed of" (W. Shakespeare). The energy criterion is the most inconvenient and obscure of all. The energy values ​​for this criterion are always calculated, because, as a rule, it is impossible to select the corresponding non-aromatic molecule for comparison. Therefore, one should be calm about the fact that there are many different estimates of the delocalization energy even for classical aromatic molecules, and for more complex systems these values ​​are completely absent. One can never compare different aromatic systems in terms of delocalization energies - one cannot conclude that molecule A is more aromatic than molecule B, because the delocalization energy is greater. Structural - a very important, if not the most important, criterion, since it has not a theoretical, but an experimental nature. The specificity of the geometry of the molecules of aromatic compounds lies in the tendency to coplanar arrangement of atoms and alignment of bond lengths. Benzene has perfect alignment of bond lengths - all six C-C bonds are the same in length. For more complex molecules, the alignment is not perfect, but significant. As a criterion, a measure of the relative deviation of the lengths of conjugated bonds from the average value is taken. The closer to zero the better. This quantity can always be analyzed if structural information is available (experimental or from high-quality quantum-chemical calculations). The trend towards coplanarity is due to the advantage of collinear axes of atomic R-orbitals for their effective overlap. The question arises: what deviation from the planar arrangement is permissible without loss of aromaticity? Examples of plane distortion in aromatic molecules are given in the lecture, they can also be found in the specialized literature (see below, p. 20). Magnetic (the presence of a ring current is a diatropic system, the effect on the chemical shifts of protons outside and inside the ring, examples are benzene and -annulene). The most convenient and accessible criterion, since the 1 H NMR spectrum is sufficient for its evaluation. For an accurate determination, theoretical calculations of chemical shifts are used. What is diatropism? Chemical - a tendency to substitution reactions, not addition. The most obvious criterion that clearly distinguishes the chemistry of aromatic compounds from the chemistry of polyenes. But it doesn't always work. In ionic systems (for example, in cyclopentadienyl anion or tropylium cation), substitution cannot be observed. Substitution reactions sometimes take place on non-aromatic systems, and aromatic systems are always capable of addition reactions to some extent. Therefore, it is more correct to call the chemical criterion a SIGN of aromaticity.

8. THE CONCEPT OF AROMATICITY. SIGNS AND CRITERIA OF AROMATICITY. - Comments

Aromaticity - a concept that characterizes a set of special structural, energy and magnetic properties, as well as features of the reactivity of cyclic structures with a system of conjugated bonds.

Although aromaticity is one of the most important and most fruitful concepts in chemistry (not only organic), - there is no commonly accepted short definition this concept. Aromaticity is understood through a set of special features (criteria) inherent in a number of cyclic conjugated molecules to one degree or another. Some of these criteria are of an experimental, observable nature, but the other part is based on the quantum theory of molecular structure. Aromaticity has a quantum nature. It is impossible to explain aromaticity in terms of classical structural theory and resonance theory.

Do not do it confuse aromaticity with delocalization and conjugation. Polyene molecules (1,3-butadiene, 1,3,5-hexatriene, etc.) show a pronounced tendency to electron delocalization (see 1st semester, diene chemistry) and the formation of a single conjugated electronic structure, which manifests itself in spectra (first of all, electronic absorption spectra), some change in the lengths and orders of bonds, energy stabilization, special chemical properties (electrophilic 1,4-addition in the case of dienes, etc.). Delocalization and conjugation are necessary but not sufficient conditions for aromaticity. Aromaticity can be defined as the property in which the conjugated ring of unsaturated bonds exhibits greater stability than would be expected with only one conjugation. However, this definition cannot be used without experimental or calculated data on the stability of the cyclic conjugated molecule.

For a molecule to be aromatic, it must contain at least one cycle, everyone from the atoms of which it has a suitable for the formation of an aromatic system R-orbital. Aromatic in the full sense of the word is considered (if the criteria listed below) is precisely this cycle (ring, ring system).

There should be 4n+2 (that is, 2, 6, 10, 14, 18, 22, etc.) electrons in this cycle.

This rule is called Hückel's aromaticity rule or criterion. The source of this rule is the highly simplified quantum-chemical calculations of idealized cyclic polyenes, made at the dawn of the development of quantum chemistry. Further research has shown that, fundamentally, this simple rule gives correct aromaticity predictions even for very complex real systems.

The rule, however, must be used correctly, otherwise the forecast may be incorrect. General recommendations are given below.

Molecule containing at least one aromatic ring has the right to be called aromatic, but this generalization should not be abused. So, it is obvious that styrene contains a benzene ring, and therefore can be called an aromatic molecule. But we may also be interested in the ethylene double bond in styrene, which has no direct relation to aromaticity. From this point of view, styrene is a typical conjugated olefin.

Never forget that chemistry is an experimental science, and no theoretical reasoning can replace or replace knowledge of the real properties of substances. Theoretical concepts, even as important as aromaticity, only help to better understand these properties and make useful generalizations.

What orbitals are considered suitable for the formation of an aromatic system?– Any orbitals perpendicular to the plane of the cycle, and

a) owned included in the cycle multiple (endocyclic double or triple) bonds;

b) corresponding to lone pairs of electrons in heteroatoms (nitrogen, oxygen, etc.) or carbanions;

c) corresponding to six-electron (sextet) centers, in particular carbocations.

Please note that the listed fragments a), b), c) give an even number of electrons to the total system: any multiple bonds - 2 electrons, lone pairs - 2 electrons, vacant orbitals - 0 electrons.

What is unsuitable or does not contribute to the aromatic system:

a) onium forms of cation centers- that is, cations containing a full octet of electrons. In this case, such a center breaks the conjugated system, for example, N-methylpyrrole is aromatic (6 electrons in the cycle), and N,N-dimethylpyrrolium is non-aromatic (ammonium nitrogen does not contribute to the π-system):

Attention - if the onium center is part of a multiple bond, then it is the multiple bond that is involved in the formation of the aromatic system, therefore, for example, N-methylpyridinium is aromatic (6 π-electrons, two from each of the three multiple bonds).

A very great help in considering similar systems is the concept isoelectronicity. Isoelectronic systems are usually similar in terms of aromaticity. In this sense, for example, N-methylpyridinium is isoelectronic to methylbenzene. Both are obviously aromatic.

b) lone pairs lying in the plane of the ring. On a single atom, only one π orbital can contribute to an aromatic system. Therefore, in the cyclopentadienyl anion, the carbanion center contributes 2 electrons, and in the phenyl anion, the carbon atom of the carbanion center contributes 1 electron, as in the benzene molecule. The phenyl anion is isoelectronic to pyridine, and the cyclopentadienyl anion is isoelectronic to pyrrole.

All are aromatic.

c) Exocyclic double bond or radical center. Such structures are usually non-aromatic, although each such structure needs special consideration with the involvement of real experimental data .

For example, quinones are non-aromatic, although a) they have flat, fully conjugated rings containing 6 electrons (four from the two multiple bonds in the ring plus two from the two exocyclic bonds).

The presence in some conjugated structure of the so-called quinoid fragments, that is, bond systems with two exocyclic double bonds, is always a source of instability and favors processes that transform the system with the quinoid fragment into a normal aromatic system. So, anthracene is a 14-electron aromatic system containing a quinoid fragment, therefore, anthracene easily adds bromine or dienophiles, since there are already two full-fledged aromatic benzene rings in the products:

Aromaticity of polycyclic structures is a rather difficult theoretical problem. From a formal point of view, if a system contains at least one benzene ring, then it can be considered aromatic. Such an approach, however, does not make it possible to consider the properties of the molecule as a whole.

The modern approach to polycyclic systems is to find in them all possible aromatic subsystems, starting with the largest - the outer contour. In this sense, for example, naphthalene can be represented as a common 10-electron system (outer loop) and two identical 6-electron benzene rings.

If the outer contour is not aromatic, then smaller aromatic contours should be sought. So, for example, diphenylene has 12 electrons in the outer contour, which does not correspond to Hückel's rule. However, we can easily find two practically independent benzene rings in this compound.

If bicyclic hydrocarbons are planar and have conjugated double bonds, Hückel's rule works for bi- and polycyclic hydrocarbons that have one bond in common ( naphthalene, anthracene, phenanthrene, etc., as well as azulene). Hückel's rule does not work well for condensed cycles that have a carbon atom common to 3 cycles. The rule for counting pairs of electrons by the method of "going around the perimeter, or along one of the contours" can help in this case, for example:

acenaphthylene pyrene perylene

sum of π-electrons: 12 16 20

including along the perimeter, 10 14 18 (along the naphthalene contour - 10 and 10)

However, for such complex cycles, this rule may not always work. Moreover, it says nothing about the actual properties of the molecule. For example, acenaphthylene has a regular double bond between atoms 1 and 2.

Various examples of isoelectronic aromatic heterocycles.

PYRROLE – FURAN – THIOPHENE (6π electrons) .

PYRIDINE– PYRIDINIUM– PYRILIUS (6π electrons) .

Pyridazine - PYRIMIDINE– pyrazine (6 π electrons) .

Oxazoles - thiazoles - IMIDAZOL (6π electrons) .

INDOL– QUINOLINE (10π electrons) .

About "nuts" . In educational literature, aromatic cycles are often denoted by a circle inside a polygon. We note with all certainty that this way of designation should be avoided in all cases where possible. Why?

Because:

a) in complex polycyclic structures, circles do not have a definite meaning and do not allow one to understand where aromaticity lives - in separate cycles or as a whole. If you draw "nuts", for example, anthracene, then it will not be clear what is the reason for its "not-quite-aromatic" and pronounced diene properties

b) even the most classic aromatic systems such as benzene and its derivatives can exhibit non-aromatic polyene properties, for the consideration of which it is necessary to see the structure of multiple bonds.

c) it is the Kekul structure that is needed to consider the effects of substituents with the help of an indispensable tool - resonant structures. "Nut" in this respect is completely fruitless. So, using the Kekule formula, we will perfectly understand the cause of high acidity P-nitrophenol and bright yellow color P-nitrophenolate. And what are we going to do with the "nut"?

A simple "Kekul-Butler" method is preferable, corresponding to the classical theory of structure and explicitly denoting multiple bonds. Having drawn such a classical structure, you can always reason about its aromaticity or non-aromaticity using the appropriate rules and criteria. It is the classical Kekul structure that is accepted as the standard in all leading international chemical journals.

And when circles are still appropriate? To denote non-benzenoid aromatic systems, especially charged ones. In this case, the classical notation is somewhat clumsy and does not show charge delocalization.

It is also difficult to do without circles in organometallic chemistry, where aromatic systems often play the role of ligands. Try to reflect the structure of ferrocene or other complexes containing a cyclopentadienyl ligand without circles!

flatness. A ring that claims to be aromatic and contains the desired continuous system of p-orbitals must be flat(or nearly flat). This requirement is one of the most unpleasant, since it is not easy to determine "by eye" which cycle is flat and which is not. The following points can be considered as simple hints:

a) cyclic conjugated systems containing 2 or 6 electrons and satisfying the considered conditions, as a rule, planar and aromatic. Such systems are usually implemented in cycles of small and medium size (2-8 members);

b) cyclic ionic systems with the number of electrons 2, 6, 10, 14 are practically necessarily aromatic, since aromaticity is the reason for the existence and stability of such ions;

c) neutral systems with 10, 14, 18 or more electrons in one single large ring, on the contrary, almost always need additional measures to stabilize the flat structure in the form of additional bridges, since the gain in energy due to the formation of a large aromatic system does not compensate for any the energy of stress arising in macrocycles, nor the entropy lost during the formation of a single flat structure.

Attention : Reading the following paragraph is strongly discouraged for people with weak and unstable knowledge. Everyone who has a rating of less than 99 points, may skip this paragraph.

Antiaromaticity. Systems that satisfy all the conditions discussed above (flat cycles with a continuous system of π-orbitals), but the number of electrons is 4n, are considered antiaromatic - i.e. non-existent. But if in the case of aromaticity we are dealing with real molecules, then in the case of antiaromaticity the problem is more complicated. It is important to understand that a real antiaromatic system is not at a minimum, but at a maximum of potential energy, that is, it is not a molecule, but a transition state. Antiaromaticity is a purely theoretical concept that describes why some cyclic conjugated systems are either completely unstable and could not be obtained even at the cost of huge efforts, or show clear tendencies to exist in the form of an ordinary polyene with alternating single and multiple bonds.

For example, cyclobutadiene would be anti aromatic if it existed as a square molecule with bonds of the same length. But there is no such square molecule in Nature. So the correct way to say this is: the hypothetical square cyclobutadiene is antiaromatic, and That's why does not exist. Experimentally, substituted cyclobutadienes were isolated at very low temperatures, but they turned out to be typical non-aromatic dienes in structure - they had a clear difference between short double bonds and long single bonds.

Really existing planar conjugated molecules with 4n electrons are always highly reactive non-aromatic polyenes. For example, benzocyclobutadiene really exists (8 electrons in the outer circuit), but has the properties of an extremely active diene.

Antiaromatic - extremely important concept in the theory of aromaticity. The theory of aromaticity predicts both the existence of particularly stable aromatic systems and the instability of antiaromatic systems. Both of these poles are important.

Antiaromaticity is a very important concept in chemistry. All unsaturated conjugated cyclic systems containing an antiaromatic number of π-electrons always have a very high reactivity in various addition reactions.

9. Trivial examples of the synthesis of non-benzenoid aromatic ions.

Cyclopropenylium cation, tropylium cation

Cyclopentadienylide anion. Aromatic carbocyclic anions С8, С10, С14.

10. Optional: attempts to synthesize antiaromatic molecules - cyclobutadiene, cyclopentadienylium cation.

Development of the concept of aromaticity. Cyclobutadiene iron tricarbonyl. Volumetric, spherical aromaticity, homoaromaticity, etc.

11. Obtaining aromatic hydrocarbons.

1. Industrial sources- oil and coal.

Reforming. Chain: heptane - toluene - benzene - cyclohexane.

2. Laboratory methods:

a) the Wurtz-Fittig reaction (an outdated method, which is rather of historical significance, do not do it apply to problem solving)

b) catalytic trimerization of acetylene,

c) acid-catalyzed trimerization of acetone and other ketones;

d) cross-coupling, both non-catalytic using cuprates and catalytic in the presence of palladium complexes,

e) Friedel-Crafts reaction, in general, acylation with Clemmensen reduction (alkylaryl ketones) or Kizhner-Wolf (any ketones and aldehydes) should be used,

f) aromatization of any derivatives of cyclohexane, cyclohexene, cyclohexadiene under the action of sulfur (fusion, suitable only for the simplest compounds) or dichlorodicyanobenzoquinone (DDQ or DDQ, general purpose reagent).

12. Properties of the ring and aliphatic side chain in aromatic hydrocarbons.

1. Hydrogenation. When does partial hydrogenation of rings occur? Hydrogenation of functional groups (C=C, C=O) without ring hydrogenation. Examples.

2. Recovery according to Birch (Na, liquid. NH 3). Why is EtOH needed? Influence of donors and acceptors in the ring on the direction of the reaction.

3. Free radical halogenation of benzene (was at school!). Halogenation of toluene and its homologues into a side chain. Selectivity of halogenation.

4. Oxidation of the side chain and polycondensed aromatic hydrocarbons. Ozonation of benzene and other aromatic compounds.

5. Diels-Alder reaction for benzene and anthracene. Conditions.

6. Reaction of alkali metals and Mg with naphthalene and anthracene (optional).

ELECTROPHILIC SUBSTITUTION IN THE AROMATIC SERIES.

1. Why electrophilic substitution (ES)?

2. What are electrophiles and what EZ reactions will we analyze in detail? (protonation, nitration, sulfonation, halogenation, alkylation, acylation, formylation). In a month, the following will be considered: azo coupling, nitrosation, carboxylation).

3. Simplified mechanism of electrophilic substitution in the aromatic ring (without π-complexes). Arenonium ions. Similarity to an allyl cation. Drawing arenonium ions on paper - resonant structures or "horseshoe" - be sure to learn how to draw resonant structures for s-complexes, as the "horseshoe" will lead to a dead end when we get to the influence of substituents on the direction of electrophilic substitution. arene protonation.

4. Evidence for the existence of π-complexes on the example of the reaction of DCl and benzene (G. Brown 1952). Proofs for the existence of σ-complexes.

5. Generalized EZ mechanism, including the formation of π- and σ-complexes. The rate-limiting step in EZ in the benzene ring. The concept of the kinetic isotope effect. Let us recall once again what a transition state and an intermediate are.

6. Orientation during electrophilic substitution: ortho-, meta, para-, ipso. Orientators of the first and second kind. Be sure to draw resonance structures for s-complexes with different substituents. Separately analyze the effect on the structure of s-complexes of substituents with inductive and mesomeric effects, as well as a combination of multidirectional effects. Partial velocity factors. Coordinated and non-coordinated orientation. Examples of different ratios of o-/p-isomers in cases where the ring has a substituent of the 1st kind (for example, sterically hindered) or of the 2nd kind (ortho effect). NMR of benzolonium ions and some arenes.

7. Consideration of specific reactions of electrophilic substitution. Nitration. Agents. exotic agents. attack particle. Features of nitration of different classes of compounds - nitroarenes (conditions), halobenzenes (separation of o- and p-isomers. How?), naphthalene and diphenyl. Nitration of aromatic amines (protective groups, how to do about- and P- isomers? Is it possible to nitrate anilines in the m-position?). Nitration of phenol (conditions, division about- and P- isomers).

7. Sulfonation of arenes. Agents, nature of the electrophile, reversibility. Features of the sulfonation of naphthalene, toluene, phenol, aniline, protection by the sulfo group in EZ reactions.

8. Derivatives of sulfonic acids: tosyl chloride, tosylates, sulfamides. Recovery of the sulfo group.

9. Halogenation. A number of halogenating agents in descending order of activity (know at least 3 examples). The nature of the electrophile, the features of the halogenation of toluene, halobenzenes, the ability to obtain all halonitrobenzenes, the halogenation of naphthalene, biphenyl, aniline, phenol, anisole. Features of iodination. Chlorination of iodobenzene without electrophilic catalysts. Polyvalent iodine compounds (PhICl 2 , PhI=O, PhI(OAc) 2)

10. Alkylation and acylation according to Friedel-Crafts. Alkylation – 3 disadvantages, syntheses examples, reversibility, influence of halogen in RHal, agents, intramolecular alkylation, restrictions on substituents, features of alkylation of phenols and amines, synthesis of n-alkylbenzenes. Acylation - comparison with alkylation, reagents, cyclic anhydrides in acylation, intramolecular reactions, Fries rearrangement.

Table 1.

Table 2. Data on the nitration of halobenzenes.

Compound	products, %*			relative speed nitration (benzene =1)**	Partial velocity factor for about- and P- positions (benzene = 1)
	ortho	meta	pair
C 6 H 5 - F					0,054 (about) 0,783 (P)
C 6 H 5 - Cl					0,030 (about) 0,136(P)
C 6 H 5 - Br					0,033 (about) 0,116(P)
C 6 H 5 - I ***					0,205 (about) 0,648(P)

*) K. Ingold. Theoretical Foundations of Organic Chemistry M., "Mir", 1973, p. 263;

**) ibid. 247; ***) according to the latest research, the mechanism of electrophilic substitution in aryl iodides may be more complex than previously accepted.

Oh division about- and P- isomers of disubstituted arenes by crystallization.

Table 3. T. pl. about- and P-isomers of disubstituted arenes in about C.

COMPARISON OF ALKYLATION AND ACYLATION REACTIONS ACCORDING TO FRIEDEL-CRAFTS.

	ALKYLATION		acylation
REAGENT	AlkHal, AlkOH, alkenes. (No ArHal!).		Carboxylic acid halides (CA), anhydrides CA, rarely - CA
CATALYST	Lewis acids, especially b / c halides of Al, Fe, Sn, etc., BF 3, H 2 SO 4, H 3 PO 4, cation exchangers.		AlCl 3 (at least mole per mole, even more is better), H 2 SO 4, H 3 PO 4.
PRODUCT	Alkyl and polyalkylarenes.		aromatic ketones. Only one acyl group can be entered.
FEATURES AND DISADVANTAGES	Practically unsuitable due to many adverse reactions, namely: 1) polyalkylation, 2) isomerization of the starting n-alkyls into sec- and tert-alkyls. 3) isomerization of polyalkylbenzenes into a mixture or into a more stable product.		Very convenient reaction, practically not complicated by side reactions. As a rule, only a para-isomer is formed. If a P-position is occupied, then the ortho-isomer (with respect to the strongest orientant).
REVERSIBILITY	THERE IS. (see below)
APPLICATION AREA	DO NOT USE for arenes containing Type II substituents. Can be used for aryl halides.
FEATURES OF APPLICATION TO PHENOLS	UNWANTED use AlCl 3 . CAN use catalysts - H 3 PO 4, HF with alcohols as alkylating reagents.	CAcCl can be acylated at oxygen. When heated, phenol ether goes FRIS rearrangement(cat. - AlCl 3). Sometimes AcOH \ BF 3 can be used for the Fr-Cr reaction Synthesis of phenolphthalein.
FEATURES OF APPLICATION TO AROMA- CHESKIM, AMINAM	Direct alkylation is practically impossible, since AlCl 3, H 2 SO 4, H 3 PO 4, HF cannot be used (attack of AlCl 3 or H + or alkyl on nitrogen - as a result, the electron-donating properties of nitrogen decrease. Under the action of RHal, N -alkylanilines).	Nitrogen acylation takes place. The catalysts form complexes on nitrogen. Acylation is possible when using two equivalents. acylating agent and ZnCl 2 to form p-acyl-N-acylanilines.

Note:

The reversibility of the Friedel-Crafts alkylation reaction leads to the fact that all possible reactions of alkylation and dealkylation occur simultaneously in the system, and the meta position is also affected, since the alkyl group activates all position of the benzene ring, although to varying degrees.

However, due to the predominant ortho-para-orientation of the processes of alkylation and reverse dealkylation under the action of an electrophile, for example, during proton ipso attack, the least reactive and more thermodynamically stable 1,3- and 1,3 ,5-isomers, since in them the alkyls orient the proton attack under other alkyls worse:

Similar reasons determine the formation of different regioisomers during sulfonation, with the essential difference that the sulfo group is an orientant of the second kind, which makes polysulfonation more difficult.

12. FORMING - the introduction of the CHO group.

Formylation is a special case of acylation.

Many formic acid derivatives can form arenes. Formylation reactions with CO, HCN, HCO(NMe 2) 2 . The specificity of the selection of electrophilic catalysts for formylation reactions.

GATTERMAN-KOCH(1897) - ArH + CO + HCl (AlCl 3 / Cu 2 Cl 2). Does HC(O)C1 exist? What about HC(O)F?

GATTERMAN- HCN b \ w + Hc1 gas. Cat. AlCl 3 or ZnCl 2 .

Gutterman-Adams(optional) - Zn(CN) 2 + HCl. You can use 1.3.5. triazine, / HC1 / A1C1 3 (optional), or C1 2 CHOR (for 5+++)

Guben-Gesh(acylation with RCN, HCl and ZnCl 2).

FORMYLING ACCORDING TO WILSMEYER-HAACK. Only electron-enriched arena! + DMF + ROS1 3 (you can SOCl 2, COCl 2).

13. Hydroxymethylation reaction, condensation of carbonyl compounds with arenes (DDT, diphenylolpropane), chloromethylation.

14. Applicability of formylation and hydroxymethylation reactions.

Gutterman-Koch - alkylbenzenes, benzene, halobenzenes.

Gutterman - activated arenes, toluene.

Vilsmeier-Haack - only activated arenas

Chloromethylation - phenol, anisole, alkyl- and halobenzenes.

Hydroxymethylation - activated arenes.

(Activated arenes are anilines, phenol, and phenol esters.)

15. Triarylmethane dyes. Crystal violet (4-Me 2 N-C 6 H 4) 3 C + X -. Synthesis from p-Me 2 N-C 6 H 4 CHO + 2 Me 2 NPh + ZnCl 2 → LEUKO FORM (white color). Further oxidation (PbO 2 or other oxidizing agent) to tert- alcohol, then acid treatment, the appearance of color.

OPTIONAL MATERIAL.

1) Mercurization of benzene with Hg(OAc) 2 Hexamercuration of benzene with Hg(OAc F) 2. Preparation of hexaiodobenzene.

2) Decarboxylation of aromatic acids ArCOOH (heating with copper powder in quinoline) = ArH + CO 2 . If there are electron-withdrawing groups in the ring, then you can simply heat the arene carboxylic acid salt very strongly. If there are donors, especially in the ortho position, it is possible to replace the carboxyl group with a proton, but this is rare!

3) Exotic electrophiles in reactions with arenes: (HN 3 / AlCl 3 - gives aniline), R 2 NCl / AlCl 3 gives R 2 NAr) (SCl 2 / AlCl 3 gives Ar 2 S. Rhodanization of aniline or phenol with dirodane (SCN) 2. Formation of 2-aminobenzothiazoles.

4) There are a large number of "tricky" reactions that are impossible to remember and not necessary, for example PhOH + TlOAc + I 2 = o-iodophenol, or PhOH + t-BuNH 2 + Br 2, -70 o C = o-bromophenol

NUCLEOPHILIC SUBSTITUTION IN THE AROMATIC SERIES.

Why is nucleophilic substitution in arenes that do not contain strong electron-withdrawing groups very difficult?

1. S N Ar– ACCESSION-DETACHMENT.

1) The nature of the intermediate. Meisenheimer complexes. (Conditions for stabilization of the intermediate.) 13 C NMR, ppm: 3(ipso), 75.8(o), 131.8(m), 78.0(n).

2) Nucleophiles. Solvents.

3) Mobility series of halogens. F (400)>>NO 2 (8)>Cl(1) ≈ Br(1.18)>I (0.26). limiting stage.

4) A series of activating ability of substituents (in what position?) NO 2 (1)> MeSO 2 (0.05)> CN (0.03)> Ac (0.01).

5) Examples of specific reactions and specific conditions.

6) Optional: the possibility of replacing the NO 2 group. Selective substitution of NO 2 groups. Spatial factors.

7) Nucleophilic substitution of hydrogen in di- and trinitrobenzene. Why is an oxidizer needed?

2. ARINE mechanism - (DESCRIPTION-ACCESSION).

Labeled chlorobenzene and ortho-chlorotoluene, potassium or sodium amides in liquid NH 3 . Mechanism.

Hydrolysis of o-, m-, and p-chlorotoluene, NaOH, H 2 O, 350-400 o C, 300 atm. VERY HARD CONDITIONS!

The importance of the inductive effect. The case of o-chloranisole.

The slow stage is proton abstraction (if Hal=Br, I) or halide anion abstraction (if Hal=Cl, F). Hence the unusual mobility series of halogens:Br>I> Cl>F

Methods for generating dehydrobenzene. The structure of dehydrobenzene - in this particle No triple bond! Capture of dehydrobenzene.

3. MechanismS RN1. Pretty rare mechanism. Generation of radical anions - electric current, or irradiation, or metallic potassium in liquid ammonia. Reactivity ArI>ArBr. A few examples. What nucleophiles can be used? Application S RN1 : reactions for a-arylation of carbonyl compounds via enolates.

4. Nucleophilic substitution in the presence of copper. Synthesis of diphenyl ether, triphenylamine, hydrolysis of o-chloranisole.

5. A few rare examples. Synthesis of salicylic to-you from benzoic, nucleophilic substitution in hexafluorobenzene.

6. S N 1 Ar – see topic "Diazo compounds".

Further reading on the topic "Aromatic compounds"

M.V. Gorelik, L.S. Efros. Fundamentals of chemistry and technology of aromatic compounds. M., "Chemistry", 1992.

NITRO COMPOUNDS.

A minimum of knowledge on aliphatic nitro compounds.

1. SYNTHESIS: a) direct nitration in the gas phase - only the simplest ones (1 semester, topic - alkanes).

b) RBr + AgNO 2 (ether) = RNO 2 (I) + RONO (II). The ratio of I and II depends on R: R perv. 80:10; R second. 15:30. R tert 0:10:60 (E2, alkene). You can use NaNO 2 in DMF. Then the amount of RNO 2 is greater even for secondary R. Method b) is good for RX active in S N 2-substitution, for example, ClCH 2 COONa + NaNO 2 in water at 85 o C. (topic: nucleophilic substitution and ambident anions, 1 semester).

c) A NEW SYNTHESIS METHOD– oxidation of the amino group with CF 3 CO 3 H(from (CF 3 CO) 2 O + H 2 O 2 in CH 2 Cl 2 or MeCN). Suitable for aliphatic and aromatic amines. Sometimes you can take m-CHNBA (m-chloroperbenzoic acid, m-CPBA, commercial reagent). DO NOT TAKE KMnO 4 or K 2 Cr 2 O 7 FOR OXIDATION! Especially for aromatic amines!

2. PROPERTIES. The most important property is high CH-acidity, tautomerism of the nitro and aci forms (pKa MeNO 2 10.5). Equilibrium is established slowly! Both forms react with NaOH, but only the aci form reacts with soda! (Ganch).

High CH-acidity makes nitro compounds analogous to enolizable carbonyl compounds. The acidity of nitromethane is close to the acidity of acetylacetone, and not simple aldehydes and ketones, therefore rather weak bases are used - alkalis, alkali metal carbonates, amines.

The Henri (Henry) reaction is an analogue of aldol or croton condensation. Since the Henri reaction is carried out under mild conditions, the product is often a nitroalcohol (analogous to an aldol) rather than a nitroolefin (analogous to a croton product). RCH 2 NO 2 is always the CH component!

Michael and Mannich reactions for RNO 2 . Optional: halogenation in NaOH, nitrosation, alkylation of anions.

RESTORATION OF AROMATIC COMPOUNDS.

1) The most important intermediate products of the reduction of nitrobenzene in an acidic environment (nitrosobenzene, phenylhydroxylamine) and an alkaline environment (azoxybenzene, azobenzene, hydrazobenzene).

2) Selective reduction of one of the nitro groups in dinitrobenzene.

3) THE MOST IMPORTANT PROPERTIES OF THE PRODUCTS OF INCOMPLETE REDUCTION OF NITROARENES.

3a) Benzidine rearrangement (B.P.).

YIELD 85% for benzidine. (R, R' = H or other substituent). PAY ATTENTION TO THE POSITION OF R AND R’ before and after regrouping!

Another 15% are by-products - mainly diphenylin (2,4'-diaminodiphenyl) and ortho-benzidine.

Kinetic equation: V=k[hydrazobenzene] 2– as a rule, protonation at both nitrogen atoms is necessary.

Benzidine rearrangement is an intramolecular reaction. Proof. Mechanism - concerted -sigmatropic rearrangement. Agreed process for benzidine.

If one or both para-positions of the starting hydrazobenzenes are occupied (R=Hal. Alk, AlkO, NH 2 , NMe 2), a semidine rearrangement can occur to form SEMIDIN OV.

Some substituents, such as SO 3 H, CO 2 H, RC(O), located in the p-position, can be cleaved off to form products of the usual B.P.

B.P. used in the production of azo dyes, diamines, e.g. benzidine, tolidine, dianisidine. Discovered by N.N. Zinin in 1845

Benzidine is a carcinogen.

4) AZOBENZONE Ph-N=N-Ph. Syn-anti-isomerism.

AZOXYBENZENE Ph-N + (→O -) \u003d N-Ph. (Task: synthesis of unsymmetrical azo- and azoxybenzenes from nitrosoarenes and aromatic amines or arylhydroxylamines, respectively, or synthesis of azoxybenzenes from nitrobenzenes and aromatic amines (NaOH, 175 o C).

5) PHENYLHYDROXYLAMINE. rearrangement in an acidic medium.

On 5 +: related rearrangements: N-nitroso-N-methylaniline (25 o C), N-nitroaniline (10 o C, was), Ph-NH-NH 2 (180 o C). The mechanism is usually intermolecular.

6) NITROSOBENZENE and its dimer.

On the reaction of nitrobenzene RMgX with the formation of alkylnitrosobenzenes and other products. This reaction shows why DO NOT MAKE Grignard reagents from halonitrobenzenes!

METHODS FOR OBTAINING AMINES,

known from the materials of previous lectures.

1. Alkylation of ammonia and amines according to Hoffmann

2. Recovery of nitriles, amides, azides, oximes.

3. Recovery of aromatic nitro compounds.

4. Rearrangements of Hoffmann, Curtius and Schmidt.

5. (Hydrolysis of amides.)

New ways.

1. Reductive amination C=O (catalytic).

2. Leuckart (Eschweiler-Clarke) reaction.

3. Gabriel synthesis,

4. Ritter reaction.

5. Catalytic arylation of amines in the presence of copper and palladium catalysts (Ullmann, Buchwald-Hartwig reactions) is the most powerful modern method for the synthesis of various amines.

Chemical properties of amines known from previous lectures.

1. Nucleophilic substitution (alkylation, acylation).

2. Nucleophilic addition to C=O (imines and enamines).

3. Elimination according to Hoffmann and according to Cope (from amine oxides).

4. Electrophilic substitution reactions in aromatic amines.

5. Basicity of amines (school curriculum).

New properties .

1. Basicity of amines (new level of knowledge). What is pK a and pK b.

2. Reaction with nitrous acid.

3. Oxidation of amines.

4. Miscellaneous– Hinsberg test, amine halogenation.

DIAZO COMPOUNDS.

1. DIAZO and AZO compounds. DIAZONIUM SALT. Anions are simple and complex. Solubility in water. explosive properties. Charge distribution on nitrogen atoms. covalent derivatives.

2. Diazotization of primary aromatic amines. Mechanism of diazotization (simplified scheme using H + and NO +). How many moles of acid are required? (Formally - 2, in reality - more.) Side formation of triazenes and side azo coupling.

3. Diazotizing agents in decreasing order of their reactivity.

NO + >>H 2 NO 2 + >NOBr>NOCl>N 2 O 3 >HNO 2.

4. Nitrosation second. and tert. amines. Reaction of aliphatic amines with HNO 2 .

5. Methods of diazotization: a) classical, b) for low-basic amines, c) reverse order of mixing, d) in a non-aqueous medium - using i-AmONO. Peculiarities of diazotization of phenylenediamines. control of the end of the reaction.

6. Behavior of diazonium salts in an alkaline medium. Diazohydrate, syn- and anti-diazotates. The ambivalence of diazotates.

7. Reactions of diazo compounds with nitrogen evolution. 1) Thermal decomposition of aryldiazonium proceeds through highly reactive aryl cations. The substitution mechanism in this case is similar to S N 1 in aliphatic chemistry. According to this mechanism, the Schiemann reaction and the formation of phenols and their ethers proceed. 2) Nucleophiles are reducing agents. The mechanism is electron transfer and the formation of an aryl radical. According to this mechanism, the reaction proceeds with the iodide ion, the replacement of the diazo group by hydrogen. 3) Reactions in the presence of copper powder or copper(I) salts. They also have a radical nature, copper plays the role of a reducing agent. The nucleophile is transferred to the aryl radical in the coordination sphere of the copper complexes. Most of these reactions are in the chemistry of diazonium salts. The Sandmeyer reaction and its analogues. 4) Nesmeyanov's reaction. 5) Diaryliodonium and bromonium salts.

8. Reactions of diazo compounds without nitrogen evolution. Recovery. Azo coupling, requirements for azo and diazo components. Examples of azo dyes (methyl orange).

9. Gomberg-Bachmann and Meyerwein reactions A modern alternative is cross-coupling reactions catalyzed by transition metal complexes and the Heck reaction. On 5++: cross-coupling with diazonium salts and diaryliodonium salts.

10. DIAZOMETHANE. Obtaining, structure, reactions with acids, phenols, alcohols (difference in conditions), with ketones and aldehydes.

Phenols and Quinones.

Most of the most important methods for the synthesis of phenols are known from the materials of previous lectures:

1) synthesis through Na-salts of sulfonic acids;

2) hydrolysis of aryl chlorides;

3) through diazonium salts;

4) cumene method.

5) hydroxylation of activated arenes according to Fenton.

PROPERTIES OF PHENOLS.

1) Acidity; 2) synthesis of esters; 3) electrophilic substitution (see the topic "Electrophilic substitution in arenes");

4) Electrophilic substitution reactions not previously considered: Kolb carboxylation, Reimer-Thiemann formylation, nitrosation; 5) tautomerism, examples; 6) Synthesis of ethers; 6a) synthesis of allyl ethers; 7) Claisen rearrangement;

8) oxidation of phenols, aroxyl radicals; Bucherer reaction;

10) conversion of PhOH to PhNR 2 .

QUINONS.

1. The structure of quinones. 2. Obtaining quinones. Oxidation of hydroquinone, semiquinone, quinhydrone. 3. Chloranil, 2,3-dichloro-5,6-dicyano-1,4-quinone (DDQ). 4. Properties of quinones: a) redox reactions, 1,2- and 1,4-addition, Diels-Alder reaction.

THE MOST IMPORTANT NATURAL ENOLS, PHENOLS AND QUINONES.

VITAMIN C (1): Vitamin C. Reducing agent. Staining with FeCl 3 . In nature, it is synthesized by all chlorophyll-containing plants, reptiles and amphibians, and many mammals. Man, monkeys, guinea pigs in the course of evolution have lost the ability to synthesize it.

The most important functions are the construction of intercellular substance, tissue regeneration and healing, the integrity of blood vessels, resistance to infection and stress. COLLAGEN SYNTHESIS (hydroxylation of amino acids). (Collagen is our everything: skin, bones, nails, hair.) Norepinephrine synthesis. Vitamin C deficiency - scurvy. Vitamin C content: black currant 200 mg/100 g, red pepper, parsley - 150-200, citrus fruits 40-60, cabbage - 50. Need: 50-100 mg/day.

tannin it gallic acid glycoside (2). Contained in tea, has tanning properties

RESVERATROL(3) - found in RED WINE (French). Reduces the likelihood of cardiovascular disease. Inhibits the formation of the endothelin-1 peptide, a key factor in the development of atherosclerosis. Promotes the promotion of French wine on the market. Over 300 publications over the past 10 years.

CLOVE OIL: eugenol (4).

VITAMIN E (5)(tocopherol - "I bear offspring"). Antioxidant. (itself forms inactive free radicals). Regulates the exchange of selenium in glutathione peroxidase, an enzyme that protects membranes from peroxides. With a deficiency - infertility, muscular dystrophy, decreased potency, increases the oxidizability of lipids and unsaturated fatty acids. Contained in vegetable oils, lettuce, cabbage, yolk, cereals, oatmeal (hercules, muesli). The requirement is 5 mg/day. Avitaminosis is rare.

VITAMINS K GROUP (6). Regulation of blood clotting and bone mineralization (carboxylation of the glutamic acid residue in position 4 (as part of proteins!)) - result: calcium binding, bone growth. Synthesized in the intestine. The need is 1 mg / day. Hemorrhagic diseases. Antivitamins K. Dicoumarin. Decreased blood clotting in thrombosis.

UBIKHINON("ubiquitous quinone"), also known as coenzyme Q (7). Electron transfer. tissue respiration. Synthesis of ATP. Synthesized in the body.

CHROMONE (8) and FLAVON (9)– semiquinones, half-esters of phenols.

QUERCETIN (10). RUTIN - vitamin P (11)(this is quercetin + sugar).

Permeability Vitamin. With a lack of bleeding, fatigue, pain in the limbs. Communication of vitamins C and P (ascorutin).

ANTHOCYANINS(from Greek: coloring of flowers).

WHAT IS LIGNIN? What is wood made of? why is it hard and waterproof?

"ALICYCLES", 2 lectures.

1. Formal classification of cycles(Heterocycles and carbocycles, both can be aromatic and non-aromatic. Non-aromatic carbocycles are called alicycles.

2. Distribution in nature (oil, terpenes, steroids, vitamins, prostaglandins, chrysanthemum acid and pyrethroids, etc.).

3. Synthesis - the end of the XIX century. Perkin Jr. - from sodium malonic ether. (see item 13). Gustavson:

Br-CH 2 CH 2 CH 2 -Br + Zn (EtOH, 80°C). This is 1,3 elimination.

4. BAYER (1885). Theory of stress. This is not even a theory, but a discussion article: According to Bayer – all cycles are flat. Deviation from the angle 109 about 28 '- voltage. The theory lived and lived for 50 years, then died, but the term remained. The first syntheses of macro- and medium cycles (Ruzicka).

5. TYPES OF VOLTAGE IN CYCLES: 1) ANGULAR (only small cycles), 2) TORSION (shielded), TRANSANNULAR (in medium cycles).

Eg. according to Bayer
Eg. according to D H o f kcal/m (therm. image)
Eg. by D H o f kcal/m: C 9 (12.5 kcal/m), C 10 (13 kcal/m), C 11 (11 kcal/m), C 12 (4 kcal/m), C 14 (2 kcal/m).
Heat of combustion per CH 2 group, kcal/m	SMALL CYCLES 166.6 (C3), 164.0 (C4)		REGULAR 158.7 (C5), 157.4 (C6)		MIDDLE TO C 12 (C 13) MACROCYCLES > C 13

6. CYCLOPROPANE. Structure(C-C 0.151 nM, P HCH = 114 o), hybridization ( according to calculations for C-H, it is closer to sp 2, for C-C - to sp 5 ), banana bonds, angle 102 o similarity with alkenes, TORSION stress - 1 kcal / m per C-H, i.e. 6 kcal/m from 27.2 (table). Acidity CH - pKa as in ethylene = 36-37, possible conjugation of the cyclopropane fragment with R-orbitals of neighboring fragments (stability of cyclopropylmethyl carbocation) .

FEATURES OF CHEMICAL PROPERTIES. 1. Hydrogenation in C 3 H 8 (H 2 /Pt, 50 o C) / 2. with wet HBr - opening of the methylcyclopropane ring according to Markovnikov, 1,5-addition to vinylcyclopropane 3. Radical halogenation. 4. Resistance to some oxidizing agents (neutral KMnO 4 solution, ozone). In phenylcyclopropane, ozone oxidizes the Ph ring to form cyclopropanecarboxylic acid.

7. CYCLOBUTANE. Structure(C-C 0.155 nM, P HCH = 107 o) , CONFORMATION - folded, deviation from the plane is 25 o. TORSION stress.

Almost not FEATURES OF CHEMICAL PROPERTIES: Hydrogenation in C 4 H 10 (H 2 /Pt, 180 about C). Features of the structure of oxetanes: TORSION stress - 4 kcal/m instead of 8.

8. CYCLOPENTANE. Almost no corner stress. In the flat one, there are 10 pairs of eclipsed C-H bonds (this could give a torsional stress of 10 kcal/m, but cyclopentane is not flat). Conformations: open ENVELOPE - semi-chair - open ENVELOPE. PSEUDO-ROTATION - a compromise between angular and torsional stress.

9. CYCLOHEXANE - ARMCHAIR. There is no angular or torsional stress. Axial and equatorial atoms. All C-H bonds of neighboring carbon atoms are in a hindered position. The transition between the two possible chair conformations through the twist form, etc. 10 5 times per second NMR spectrum of cyclohexane. Fast and slow exchange processes in NMR.

MONOSUBSTITUTED CYCLOHEXANES. conformers. Axial and gosh-butane interactions.

Free conformational energies of substituents.– D G o, kcal/m: H(0), Me(1.74, this is ~ 95% e-Me conformer in equilibrium), i-Pr(2.1), t-Bu (5.5), Hal (0.2-0.5) Ph (3.1).

Tret-butyl group as an anchor, fixing the conformation in which it itself occupies an equatorial position. AT tert-butylcyclohexane at room temperature more than 99.99% of the equatorial conformer.

anomeric effect. Opened on monosaccharides and will be discussed in more detail there.

10. DISUBSTITUTED CYCLOHEXANES. Cis-trans isomers, enantiomers for 1,2-. 1,3-. 1,4-disubstituted cyclohexanes.

11. EFFECT OF CONFORMATIONAL STATE ON REACTIVITY. Recall the elimination in menthyl and isomentyl chloride (1 sem). Bredt's rule.

12. The concept of conformations of middle cycles (bath chairs, crowns, etc.)transannular tension. The concept of transannular reactions.

13. Methods for the synthesis of small cycles.

14. SYNTHESIS OF ORDINARY AND AVERAGE CYCLES.

Through the malonic ether.

Pyrolysis of Ca, Ba, Mn, Th salts of a,w-dicarboxylic acids.

Diekmann condensation.

Through a, w - dinitriles.

acyloin condensation.

Alkene metathesis.

Cyclotri- and tetramerization on metal complex catalysts.

Demyanov's reaction.

15. Features of the structure of cycloalkenes.

16. Synthesis of cycloalkynes.

17. Bicycles. Spirany. Adamantane.

18. Exotic. Tetrahedran, Cuban, Angulan, Propellan.

HETEROCYCLIC COMPOUNDS.

1. Five-membered heterocycles with one heteroatom.

Pyrrole, furan, thiophene, aromaticity, their derivatives in nature (porphyrin, heme, chlorophyll, vitamin B 12, ascorbic acid, biotin).

2. Methods for the synthesis of five-membered heterocycles with one heteroatom. Paal-Knorr method. Synthesis of pyrrole according to Knorr and furan according to Feist-Benary. Furan transformations into other five-membered heterocycles according to Yuriev. Obtaining furfural from plant waste containing five-carbon carbohydrates (pentosans).

3. Physical and chemical properties of five-membered heterocycles.

1H and 13C NMR data, δ ppm (for benzene δН 7.27 and δС 129 ppm)

Dipole moments

3.1 Electrophilic substitution in pyrrole, furan and thiophene.

In terms of reactivity with respect to electrophiles, pyrrole resembles activated aromatic substrates (phenol or aromatic amines), pyrrole is more reactive than furan (rate factor over 105), thiophene is much less reactive than furan (also about 105 times), but more reactive than benzene (rate factor 10 3 -10 5). All five-membered heterocycles tend to polymerize and resinify in the presence of strong protic acids and highly reactive Lewis acids. Pyrrole is especially acidophobic. FOR ELECTROPHILIC SUBSTITUTION IN FIVE-MEMBERED HETEROCYCLES, ESPECIALLY PYRROL, IT IS IMPOSSIBLE TO TAKE STRONG MINERAL ACIDS, AlCl 3, AS WELL AS STRONG OXIDIZERS! Although this rule is not absolute, and the thiophene is somewhat resistant to acids, it is easier and safer to avoid such reactions altogether for all donor heterocycles. Examples of electrophilic substitution reactions in pyrrole, furan and thiophene.

3.2. Basicity and acidity of pyrrole, alkylation of Li, Na, K and Mg pyrrole derivatives.

3.3. Condensation of pyrrole with aldehydes (formylation, formation of porphyrins).

3.4. Features of the chemical properties of furans (reaction with bromine, Diels-Alder reaction.

3.5. Features of the chemical properties of thiophene. Desulfurization.

3.6. Reactions of C-metallated five-membered heterocycles.

4. Fused five-membered heterocycles with one heteroatom.

4.1. Indoles in nature (tryptophan, skatole, serotonin, heteroauxin. Indigo.)

4.2 Synthesis of indoles according to Fischer. Mechanism.

4.3 Comparison of the properties of indole and pyrrole. Similar to pyrrole indole is acidophobic and very sensitive to oxidizing agents. A significant difference from pyrrole is the orientation of the electrophilic substitution to position 3.

5. Five-membered heterocycles with two heteroatoms. Imidazole, amphotericity, tautomerism, use in acylation. Comparison with amidines. Imidazole is a hydrogen bond donor and acceptor. This is important for the chemistry of enzymes such as chymotrypsin. It is the histidine fragment of chymotrypsin that transfers the proton and provides hydrolysis of the peptide bond.

6. Pyridine, aromaticity, basicity ( pKa 5.23; basicity comparable to aniline (pKa = 4.8), but slightly higher). pKa of pyridine derivatives: 2-amino-Py= 6,9 , 3-amino-Ru = 6,0 . 4-amino-Py = 9.2. This is a pretty strong foundation. 4-nitro-Py = 1.6; 2-cyano-Py=-0.26).

Derivatives of pyridine in nature (vitamins, nicotine, NADP).

6.1. 1Н NMR spectra data (13 С), δ, ppm

6.2. Methods for the synthesis of pyridines (from 1,5-diketones, three-component Hantzsch synthesis).

6.3. Chemical properties of pyridine. Alkylation, acylation, DMAP, complexes of pyridine with Lewis acids. (cSO 3 , BH 3 , NO 2 + BF 4 - , FOTf). Mild electrophilic reagents for sulfonation, reduction, nitration and fluorination, respectively.

6.4. Electrophilic substitution reactions for pyridine. Features of reactions and examples of conditions for electrophilic substitution in pyridine.

6.5. Pyridine N-oxide, preparation and its use in synthesis. Introduction of a nitro group into the 4 position of the ring.

6.6. Nucleophilic substitution in 2-, 3-, and 4-chloropyridines. Partial rate factors compared to chlorobenzene.

A similar trend is observed for 2-, 3-, and 4-haloquinolines.

6.7. Nucleophilic substitution of the hydride ion:

reaction of pyridine with alkyl or aryllithium;

reaction of pyridine with sodium amide (Chichibabin reaction). Since the elimination of the free hydride ion is impossible for energy reasons, in the Chichibabin reaction, the intermediate sigma complex is aromatized due to interaction with the reaction product to form the sodium salt of the product and molecular hydrogen.

In other reactions, the hydride is usually removed by oxidation. So, pyridinium salts can undergo hydroxylation leading to the formation of 1-alkylpyridones-2. The process is similar to amination, but in the presence of an oxidizing agent, for example, K 3 .

6.8. lithium derivatives of pyridine. Receiving, reactions.

6.9. Pyridine nucleus as a strong mesomeric acceptor. Stability of carbanions conjugated to the pyridine nucleus in 2- or 4-positions. Features of the chemical properties of methylpyridines and vinylpyridines.

7. Fused six-membered heterocycles with one heteroatom.

7.1. Quinoline. Quinine.

1H NMR spectra (13C) of quinoline, δ, ppm

7.1. Methods for obtaining quinolines. Syntheses of Skraup and Döbner-Miller. The concept of the mechanism of these reactions. Synthesis of 2- and 4-methylquinolines.

7.2. isoquinolines,Bischler-Napiralsky synthesis .

7.3. Chemical properties of quinolines and isoquinolines. Comparison with pyridine, differences in the properties of pyridine and quinoline.

Behavior of heterocyclic compounds in the presence of oxidizing and reducing agents designed to modify side chains.

Reclaimers:

Pyrrole is almost unlimitedly resistant to the action of reducing agents, as well as bases and nucleophiles (for example, it withstands hydrides, borane, Na in alcohol without affecting the ring, even with prolonged heating).

Thiophene - as well as pyrrole, is resistant to the action of reducing agents, as well as bases, nucleophiles, with the exception of reducing agents based on transition metals. Any nickel compounds (Raney nickel, nickel boride) cause desulfurization and hydrogenation of the skeleton. Palladium and platinum based catalysts are usually poisoned by thiophenes and do not work.

Furan - same as pyrrole, but hydrogenates very easily.

Indole is completely analogous to pyrrole.

The pyridine ring is more easily reduced than the benzene ring. For side chains, NaBH 4 can be used, it is undesirable (often not even possible) to use LiAlH 4 .

For quinoline, the patterns are practically the same as for pyridine; LiAlH 4 cannot be used.

In the quaternized form (N-alkylpyridinium, quinolinium) they are very sensitive to reducing agents (ring reduction), bases, nucleophiles (ring opening).

Oxidizers.

The use of oxidizing agents for compounds of pyrrole, indole, and, to a lesser extent, furan, leads, as a rule, to the destruction of the ring. The presence of electron-withdrawing substituents increases resistance to oxidizing agents, but more detailed information about this is beyond the 3rd course program.

Thiophene behaves like benzene - conventional oxidizing agents do not destroy the ring. But the use of peroxide oxidants in any form is categorically excluded - sulfur is oxidized to sulfoxide and sulfone with loss of aromaticity and immediate dimerization.

Pyridine is quite stable to most oxidizing agents under mild conditions. The ratio of pyridine to heating with KMnO 4 (pH 7) to 100 o C in a sealed ampoule is the same as for benzene: the ring is oxidized. In an acidic environment in the protonated form, pyridine is even more resistant to oxidizing agents; a standard set of reagents can be used. Peracids oxidize pyridine to N-oxide - see above.

Oxidation of one of the quinoline rings with KMnO 4 leads to pyridine-2,3-dicarboxylic acid.

8. Six-membered heterocycles with several nitrogen atoms

8.1. Pyrimidine. Pyrimidine derivatives as components of nucleic acids and drugs (uracil, thymine, cytosine, barbituric acid). Antiviral and antitumor drugs - pr-pyrimidine (5-fluorouracil, azidothymidine, alkylmethoxypyrazines - components of the smell of food, fruits, vegetables, peppers, peas, fried meat. The so-called Maillard reaction (optional).

8.2. The concept of the chemical properties of pyrimidine derivatives.

Pyrimidine can be brominated at position 5. Uracil (see below) can also be brominated and nitrated at position 5.

Light reactions S N 2 Ar in chlorpyrimidines(analogy with pyridine!): 4 moves faster than 2.

Substitution of 2-C1 under the action of KNH 2 in NH 3 g. The mechanism is not aryne, but ANRORC (at 5+++).

10. Binuclear heterocycles with several nitrogen atoms. Purines ( adenine, guanine).

The most famous purines (caffeine, uric acid, acyclovir). Purine isosteres (allopurinol, sildenafil (Viagra™)).

Additional literature on the topic "Heterocycles"

1. T. Gilchrist "Chemistry of heterocyclic compounds" (Translated from English - M .: Mir, 1996)

2. J. Joule, K. Mills "Chemistry of heterocyclic compounds" (Translated from English - M.: Mir, 2004).

AMINO ACIDS .

1. Amino acids (AA) in nature. (≈ 20 amino acids are present in proteins, these are encoded AAs, >200 AAs are found in nature.)

2. α-, β-, γ-amino acids. S-configuration of natural L-amino acids.

3. Amphoteric, isoelectric point(pH is usually 5.0-6.5). Basic (7.6-10.8), acidic (3.0-3.2) amino acids. Confirmation of the zwitterionic structure. Electrophoresis.

4. Chemical properties of AK- properties of COOH and NH 2 groups. Chelates. Betaines. Behavior heating(compare with hydroxy acids). Formation of azlactones from N-acetylglycine and hydantoins from urea and AA - by 5++. Synthesis of esters and N-acylation - the path to peptide synthesis (see the lecture on protein).

5. Chemical and biochemical deamination,(mechanisms do not teach!), the principle of enzymatic transamination with vitamin B 6 (it was in the topic "Carbonyl compounds" and in the course of biochemistry).

7. The most important methods for the synthesis of amino acids:

1) from halocarboxylic acids - two primitive methods, including phthalimide. (Both already known!)

2) Strecker synthesis;

3) alkylation of CH-acid anions - PhCH=N-CH 2 COOR and N-acetylaminomalonic ester.

4) Enantioselective synthesis of AA by:

a) microbiological (enzymatic) separation and

b) enantioselective hydrogenation using chiral catalysts.

5) β-amino acids. Synthesis according to Michael.

	Hydrophobic amino acids	A little about the biochemical role (for general development)
ALANIN		The removal of ammonia from tissues to the liver. Transamination, transformation into pyruvic acid. Synthesis of purines, pyrimidines and heme.
VALIN*		If, as a result of a mutation, valine takes the place of glutamine acid in hemoglobin, there is a hereditary disease - sickle cell anemia. A serious hereditary disease common in Africa, but at the same time conferring resistance to malaria.
LEUCINE*
ISOLEUCINE*
PROLINE		Bends in protein molecules. No rotation where there is proline.
PHENYLALANINE*		If it does not turn into tyrosine, there will be a hereditary disease - phenylpyruvic oligophrenia.
TRYPTOFAN*		Synthesis of NADP, serotonin. Decay in the intestine to skatole and indole.
	Hydrophilic amino acids
GLYCINE Gly (G)	H 2 N-CH 2 -COOH	Participates in a huge number of biochemical syntheses in the body.
SERIN Ser(S)	HO-CH 2-CH(NH 2) -COOH	Participate (as part of proteins) in the processes of acylation and phosphorylation.
THREEONINE* Thr(T)	CH 3 -CH (OH) - CH (NH 2) -COOH
TYROSINE Tyr (Y)		Synthesis of thyroid hormones, adrenaline and norepinephrine
	"Acidic" amino acids
ASPARAGIC ACID Asp(D)	HOOC-CH 2-CH(NH 2) -COOH	Amino group donor in syntheses.
GLUTAMIC ACID Glu(E)	HOOC-C 4 H 2 -CH 2-CH(NH 2) -COOH	Forms GABA (γ-aminobutyric acid (aminalon) - a sedative. Glu removes NH 3 from the brain, turning into glutamine (Gln). 4-carboxyglutamic acid binds Ca in proteins.
	"A M AND D S" acidic amino acids
ASPARAGIN Asn(N)	H2N-CO-CH 2 -CH(NH 2) -COOH
GLUTAMINE Gln(Q)	H2N-CO-CH 2 -CH 2 -CH (NH 2) -COOH	Donoramino groups in syntheses
CYSTEINE Cys(C)	HS-CH 2-CH(NH 2) -COOH	Formation of S-S bonds (tert, protein structure, regulation of enzyme activity)
CYSTINE	Cys-S-S-Cys
METIONINE* Met	MeSCH 2 CH 2 - CH(NH2)COOH	Donor of methyl groups
	"Essential" amino acids
LYSINE* Lys (K)	H 2 N-(CH 2) 4 -CH (NH 2) -COOH	Forms crosslinks in collagen and elastin making them elastic.
ARGININE Arg(R) Contains a guanidine moiety	H 2 N-C (= NH) -NH- (CH 2) 3 -CH (NH 2) -COOH	Participates in the removal of ammonia from the body
HISTIDINE His(H) Residue of imidazole		Synthesis of histamine. Allergy.

* - essential amino acids. Glucose and fats are easily synthesized from most amino acids. Violations of amino acid metabolism in children leads to mental disability.

PROTECTING GROUPS USED IN PEPTIDE SYNTHESIS.

NH 2 - protective groups -

RC(O)- = ( HC(O)- ) CF 3 C(O)- phthalyl

ROC(O)- = PhCH 2 OC(O)- and substituted benzyls , t-BuOC(O)- and etc. tert-groups,

Fluorenylmethyloxycarbonyl group,

Ts-group

COOH - protecting groups - esters - PhCH 2 O- and substituted benzyls,

t-BuO- and fluorenyl methyl ethers.

A separate consideration of the protective groups for other FG amino acids is not provided.

Methods for creating a peptide bond.

1. Acid chloride (via X-NH-CH(R)-C(O)Cl). The method is outdated.

2.. Azide (according to Curtius, through X-NH-CH (R) -C (O) Y → C (O) N 3 as a mild acylating reagent.

3.Anhydrite - e.g. through mixed anhydride with carbonic acid.

4.Activated esters (for example, C (O) -OS 6 F 5, etc.)

5. Carbodiimide - acid + DCC + amine

6. Synthesis on a solid support (eg on Merrifield resin).

The biological role of peptides. A few examples .

1. Enkephalins and endorphins are opioid peptides.

e.g. Tyr-Gly-Gly-Phe-Met and

Tyr-Gly-Gly-Phe-Leu from pig brain. Several hundred analogues are known.

2. Oxytocin and vasopressin Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu -Gly-NH 2

│________________│

DuVigneaud, Nob.pr. 1955 Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Arg -Gly-NH 2

│________________│

3. Insulin controls the uptake of glucose by the cell. Excess glucose in the blood (diabetes) - leads to glycosylation of everything (mainly proteins).

4. Peptide transformations: angiotensinogen → angiotensin I → angiotensin II. One of the main mechanisms for regulating blood pressure (BP), the site of application of many drugs (ACE blockers - angiotensin-converting enzyme. Stage 1 catalyst - renin enzyme (isolated from the kidneys).

5. Peptide toxins. They act in diseases - botulism, tetanus, diphtheria, cholera. Poisons of snakes, scorpions, bees, fungal toxins (phalloidin, amantine), marine invertebrates (Conusgeographus - 13 AA, two -S-S-bridges). Many are stable when boiled in an acidic solution (up to 30 minutes).

6. Peptide antibiotics (gramicidin S).

7. Aspartame Asp-Phe-OMe is 200 times sweeter than sugar. Bitter and "tasty" peptides.

8. Proteins. Four levels of organization of a native protein molecule. A protein is a unique (along with nucleic acids) type of macromolecule that has a precisely known structure, ordered down to the details of stereochemistry and conformation. All other known macromolecules, including natural ones (polysaccharides, lignin, etc.) have a disordered structure to a greater or lesser extent - a wide distribution of molecular weights, free conformational behavior.

The primary structure is the sequence of amino acids. How briefly is the primary structure indicated?

Secondary structure - conformational-regular elements of two types (α-helices and β-layers) - only a part of the protein macromolecule is ordered in this way.

The tertiary structure is a unique ordered stereochemical configuration of a complete macromolecule. The concept of "folding" (folding) of the polypeptide chain into the tertiary structure of the protein. Prions.

Quaternary structure - connection of several subunits in proteins, consisting of several polypeptide chains. Disulfide bridges (reversible transformation of cysteine-cystine) as a way to fix the tertiary and quaternary structures.

CARBOHYDRATES.

1. What are carbohydrates? Carbohydrates around and inside of us.

2. The concept of photosynthesis of derivatives of D-glyceric acid. Only for especially outstanding students - about the formation of glyceric acid diphosphate from D-ribulose.

3. What is the D-series of carbohydrates.(Briefly about the history of the concept of D- and L-series).

4. Classification of carbohydrates: a) by the number of C atoms; b) by the presence of C=O or CHO groups; c) by the number of cyclic fragments.

5. Synthesis of carbohydrates from D-glyceraldehyde according to the Kilyani-Fischer method.How did Fischer establish the formula for glucose?

6. Derivation of formulas of all D-tetroses, -pentoses, -hexoses from D-glyceraldehyde (open structures). For all students - to know the formula of glucose (open and cyclic), mannose (2-epimer of glucose), galactose (4-epimer of glucose), ribose. pyranoses and furanoses.

7. Be able to move from an open form to a cyclic one according to Haworth. Be able to draw the formulas of α- and β-glucose (all substituents in the e-position except the anomeric one) in the chair conformation.

8. What are epimers, anomers, mutarotation. anomeric effect.

9. Chemical properties of glucose as an aldehyde alcohol: a) chelates with metal ions, obtaining glycosides, full ethers and esters, isopropylidene protection; b) oxidation of the CHO group with metal ions, bromine water, HNO 3 . Splitting by Will. Reaction with amines and getting ozone. The most important principles and methods of selective alkylation of various hydroxyls in glucose.

10. D-fructose as a representative of ketosis. Open and cyclic forms. Silver mirror reaction for fructose.

11. The concept of deoxysugars, amino sugars. This includes chitin and heparin. Septulose and octulose in avocados. Meillard's reaction (Maillard).

12. OLIGOSACCHARIDES. Maltose,cellobiose,lactose, sucrose. Reducing and non-reducing sugars.

13. Polysaccharides - starch(20% amylose + 80% amylopectin),starch iodine test, glycogen, cellulose,hydrolysis of starch in the oral cavity (amylase) and hydrolysis of cellulose,nitrocellulose, viscose fiber, paper production , blood groups and the difference between them.

THE MOST IMPORTANT POLYSACCHARIDES.

POLYSACCHARIDE	COMPOSITION and structure	notes
cyclodextrins	α-(6), β-(7), γ-(8) Consists of glucose 1-4 connections.	Excellent complexing agents, chelating agents
starch	α-glu-(1,4)-α-glu 20% amylose + 80% amylopectin	amylose= 200 glu, linear polysaccharide. Amylopectin= 1000 or more glu, branched.
glycogen	"branched" starch, participation of 6-OH	store of glucose in the body
	From leftover fructose	Contained in Jerusalem artichoke
cellulose	β-glu-(1,4)-β-glu	Cotton, plant fiber, wood
cellulose	Xanthate at 6-position	Obtaining viscose - rayon, cellophane (packaging film)
cellulose acetate	Approximately diacetate	acetate fiber
cellulose nitrate	Trinitroether	smokeless powder
Production of paper from wood	wood = cellulose + lignin. Process Ca (HSO 3) 2 or Na 2 S + NaOH	Sulfation of wood - removal of lignin into water - obtaining pulp.
	Poly-α-2-deoxy-2-N-Ac-aminoglucose (instead of 2-OH - 2-NH-Ac)	If you remove Ac from nitrogen, you get chitosan - a fashionable dietary supplement
hyaluronic acid	– (2-AcNH-glucose – glucuronic acid) n –	Lubrication in the body (eg in the joints).
	The structure is very complex - (2-HO 3 S-NH-glucose - glucuronic acid) n -	Increases blood clotting time
Chondroitin sulfate	Glycoproteins (collagen), proteoglycans, communication through NH 2 asparagine or OH serine	It is found everywhere in the body, especially in connective tissue, cartilage.

Note: Glucuronic acid: 6-COOH - 1-CHO

Gluconic acid: 6-CH 2 OH - 1-COOH

Glucaric acid: 6-COOH - 1-COOH

1. Chemistry and biochemistry of nucleic acids.

Nitrogenous bases in RNA: U (uracil), C (cytosine) are pyrimidine derivatives. A (adenine), G (guanine) - derivatives of purine. In DNA instead of Y (uracil) there is T (thymine).

Nucleosides ( sugar+ nitrogenous base): uridine, cytidine, thymidine, adenosine, guanosine.

Nucleotides( phosphate+ sugar+ nitrogenous base).

Lactim-lactam tautomerism.

Primary Structure nucleic acids (connection of nucleosides through oxygen atoms at C-3 and C-5 of ribose (deoxyribose) using phosphate bridges.

RNA and DNA.

a) Major bases and minor bases (RNA). For tRNA alone, the list of minor bases approaches 50. The meaning of their existence is protection from hydrolytic enzymes. 1-2 examples of minor bases.

c) Chargaff's rules for DNA. The most important: A=T. G=C. However, G+C< А+Т для животных и растений.

Principles of DNA structure

1. Irregularity.
There is a regular sugar-phosphate backbone to which nitrogenous bases are attached. Their alternation is irregular.

2. Antiparallelism.
DNA consists of two polynucleotide chains oriented antiparallel. The 3' end of one is opposite the 5' end of the other.

3. Complementarity (additionality).
Each nitrogenous base of one chain corresponds to a strictly defined nitrogenous base of the other chain. Compliance is given by chemistry. Purine and pyrimidine pair form hydrogen bonds. There are two hydrogen bonds in the A-T pair, and three in the G-C pair, since these bases have an additional amino group in the aromatic ring.

4. Presence of a regular secondary structure.
Two complementary, antiparallel polynucleotide chains form right-handed helices with a common axis.

Functions of DNA

1. DNA is the carrier of genetic information.
The function is provided by the fact of the existence of the genetic code. Number of DNA molecules: in a human cell - 46 chromosomes, each has one DNA molecule. The length of 1 molecule is ~ 8 (i.e. 2x4) cm. In packaged form - 5 nm (this is the tertiary structure of DNA, DNA supercoiling on histone proteins).

2. Reproduction and transmission of genetic information is provided by the process of replication (DNA → new DNA).

3. Implementation of genetic information in the form of proteins and any other compounds formed with the help of enzyme proteins.
This function is provided by the processes of transcription (DNA to RNA) and translation (RNA to protein).

Repair- repair of the damaged section of DNA. This is due to the fact that DNA is a double-stranded molecule, there is a complementary nucleotide that "tells" what needs to be fixed.

What are the errors and damages? a) Replication errors (10 -6), b) depurination, loss of purine, formation of apurine sites (loss of 5000 purine residues per day in each cell!), c) deamination (for example, cytosine turned into uracil).

induced damage. a) dimerization of pyrimidine rings under the action of UV at C=C bonds with the formation of a cyclobutane ring (photolyases are used to remove dimers); b) chemical damage (alkylation, acylation, etc.). Repair of damage - DNA glycosylase - apurinization (or apyrimidinization) of the alkyl base - further introduction of the "normal" base in five steps.

Violation of the repair process - hereditary diseases (xeroderma pigmentosa, trichothiodystrophy, etc.) There are about 2000 hereditary diseases.

Transcription and translation inhibitors are antibacterial drugs.

Streptomycin is an inhibitor of protein synthesis in prokaryotes.

Tetracyclines - "bind to the 30S subunit of the bacterial ribosome and block the attachment of aminoacyl-tRNA to the A-center of the ribosome, thereby disrupting elongation (i.e., mRNA reading and polypeptide chain synthesis)".

Penicillins and cephalosporins – β-lactam antibiotics. The β-lactam ring inhibits the synthesis of cell walls in gram-negative microorganisms.

Viruses - inhibitors of matrix synthesis in eukaryotic cells.

toxins – often do the same thing as viruses. α-Amanitin- pale grebe toxin, LD 50 0.1 mg per kg of body weight. Inhibition of RNA polymerase. The result is irreversible changes in the liver and kidneys.

Ricin - a very strong protein poison from castor beans. This is the enzyme N-glycosylase, which removes the adenine residue from the 28S rRNA of the large subunit of the ribosome, inhibits protein synthesis in eukaryotes. Found in castor oil.

Diphtheria enterotoxin (protein with a mass of 60 kDa) - inhibition of protein synthesis in the pharynx and larynx.

Interferons - proteins with a size of about 160 AA are secreted by some cells of vertebrates in response to infection with viruses. The amount of interferon - 10 -9 - 10 -12 g, i.e. one protein molecule protects one cell. These proteins, like protein hormones, stimulate the synthesis of enzymes that destroy the synthesis of viral mRNA.

Hereditary diseases (monogenic) and (not to be confused!) family predisposition to diseases (diabetes, gout, atherosclerosis, urolithiasis, schizophrenia are multifactorial diseases.)

Principles of nucleotide sequence analysis (optional).

DNA technology in medicine.

A. DNA isolation. B. Cleavage of DNA with restriction enzymes. Human DNA - 150x10 6 base pairs. They must be divided into 500,000 fragments of 300 pairs each. Next is gel electrophoresis. Next - Southern blot hybridization with a radiosonde or other techniques.

Sequencing. Exonucleases cleave one mononucleotide in sequence. This is an outdated technique.

PCR (PCR) - polymerase chain reaction. (Nobel Prize 1993: Carrie Mullis)

Principle: primers (these are DNA fragments of ~20 nucleotides - commercially available) + DNA polymerase → DNA production (amplifier) ​​→ DNA analysis (sequencer). Now everything is done automatically!

DNA sequencing method using labeled defective nucleotides (eg, dideoxynucleotides). Now the labels are not radioactive, but fluorescent. Analysis for AIDS and other STIs. Fast but expensive. Better not get sick!

The success of PCR for diagnosis and wide distribution is due to the fact that the enzymes involved in the process, isolated from heat-resistant hot spring bacteria and made by genetic engineering, withstand heat, which causes denaturation (dissociation of DNA strands) and prepare them for the next PCR cycle.

TERPENES, TERPENOIDS AND STEROIDS.

Turpentine – volatile pine resin oil.

Terpenes are a group of unsaturated hydrocarbons of composition (C 5 H 8) n, where n³ 2, widespread in nature. Contains fragments of isopentane, connected, as a rule, according to the “head to tail” type (this is the Rule of Ruzicka).

Monoterpenes C 10 (C 5 H 8) 2 Ce squee terpenes C 15, (C 5 H 8) 3 Diterpenes C 20, (C 5 H 8) 4 Triterpenes C 30, (C 5 H 8) 6. Polyterpenes (rubber).

The degree of hydrogenation of terpenes can be different, so the number of H atoms does not have to be a multiple of 8. There are no C 25 and C 35 terpenes.

Terpenes are either acyclic or carbocyclic.

Terpenoids (isoprenoids) are terpenes (hydrocarbons) + functionally substituted terpenes. An extensive group of natural compounds with a regular skeletal structure.

Isoprenoids can be classified into

1) terpenes, incl. functionally substituted

2) steroids

3) resin acids,

4) polyisoprenoids (rubber).

The most important representatives of terpenes.

Some features of the chemistry of terpenes, bicyclic molecules and steroids.

1) nonclassical cations; 2) rearrangements of the Wagner-Meyerwein type; 3) easy oxidation; 4) diastereoselective synthesis; 5) influence of remote groups.

Formally, terpenes are isoprene polymerization products, but the synthesis route is completely different! Why are polyisoprene derivatives so widespread in nature? This is due to the peculiarities of their biosynthesis from acetyl coenzyme A, i.e. actually from acetic acid. (Bloch, 40-60 years. Both carbon atoms from C 14 H 3 C 14 UN are included in terpene.)

SYNTHESIS SCHEME OF MEVALONIC ACID, the most important intermediate in the biosynthesis of terpenes and steroids.

Condensation acetyl coenzyme A in acetoacetyl coenzyme A passes through the type of Claisen ester condensation.

Synthesis of limonene from geranyl phosphate, an important intermediate both in the synthesis of a wide variety of terpenes and in the synthesis of cholesterol. Below is the conversion of limonene to camphor under the action of HCl, water and an oxidizing agent (PP is a pyrophosphate residue).

The conversion of mevalonic acid to geranyl phosphate occurs by 1) phosphorylation of 5-OH, 2) re-phosphorylation of 5-OH and the formation of pyrophosphate, 3) phosphorylation at 3-OH. All this happens under the influence of ATP, which turns into ADP. Further transformations:

Major steroid hormones.

Formed in the body from cholesterol. Cholesterol is insoluble in water. Penetrates into the cell and participates in biosynthesis through complexes with sterol-carrying proteins.

BILE ACIDS . Cholic acid. Cis-junction of rings A and B. Bile acids improve lipid absorption, lower cholesterol levels, and are widely used for the synthesis of macrocyclic structures.

STEROIDS - MEDICINES.

1. Cardiotonics. Digitoxin. Contained in various types of foxglove (Digitalispurpurea L. or DigitalislanataEhrh.) Glycosides are natural compounds that consist of one or more glucose or other sugar residues, most often associated through positions 1- or 4- with an organic molecule (AGLYCON). Substances of similar structure and action are found in the venom of some toad species.

2. Diuretics. Spironolactone (veroshpiron). Aldosterone antagonist. Blocks the reabsorption of Na + ions, thus reducing the amount of fluid, which leads to a decrease in blood pressure Does not affect the content of K + ions! It is very important.

3. Anti-inflammatory drugs. Prednisolone. 6-methylprednisolone (see formula above). Fluorosteroids (dexamethasone (9a-fluoro-16a-methylprednisolone), triamcinolone (9a-fluoro-16a-hydroxyprednisolone. Anti-inflammatory ointments.

4. Anabolics. Promotes the formation of muscle mass and bone tissue. Methandrostenolone.

5. BRASSINOSTEROIDS- NATURAL COMPOUNDS HELPING PLANTS FIGHT STRESS (drought, frost, excessive moisture) HAVE GROWTH-REGULATING ACTIVITY.

24-epibrassinolide [(22R, 23R,24R)-2α,3α,22,23-tetrahydroxy-B-homo-7-oxa-5α-ergostan-6-one.

The preparation "Epin-extra", NNPP "NEST-M".

METAL COMPLEX CATALYSIS (1 SEMESTER).

Xylene, etc.), naphthalene and its derivatives, etc.

Benzene aromatic hydrocarbons are predominantly liquids, partly solids with a characteristic aromatic odor. They are used as, as well as as starting products in the production of dyes, etc. Their pairs in high concentrations have a narcotic and partly convulsive effect.

In acute poisoning, excitation, like alcohol, is observed, then gradual depression, occasionally; death comes from respiratory arrest. Chronic poisoning is characterized by severe damage to the blood system and, accompanied by a decrease in the content in the blood, leukocytes and disorders of the nervous system, damage to the liver and organs of internal secretion. The most severe chronic poisoning causes benzene (see). Under the action of vapors or dust of aromatic hydrocarbons, clouding of the lens is observed. The irritating effect of benzene derivatives on the skin increases with the increase in the number of methyl groups, it is especially pronounced in mesitylene (trimethylbenzene). The substitution of hydrogen in the side chain for ( , ) enhances the irritating effect of aromatic hydrocarbons on the respiratory tract and mucous membranes. The toxic properties of aromatic amino and nitro compounds (see) are associated with their ability to convert oxyhemoglobin to methemoglobin.

Naphthalene and its derivatives can cause damage to the nervous system, gastrointestinal tract, kidneys, irritation of the upper respiratory tract and skin. Compounds of polynuclear aromatic hydrocarbons with condensed rings are characterized by carcinogenic activity. Tumors usually occur in places of direct contact with these aromatic hydrocarbons, but occasionally in distant organs (bladder).

Treatment of poisoning. In mild cases of acute poisoning with aromatic hydrocarbons, it is necessary to remove the victim from the work environment, treatment is usually not required (in case of excitation, valerian drops are prescribed, rest is recommended). In severe cases, when breathing is weakened, they resort to; the victim is given to inhale oxygen or carbogen. For circulatory disorders - a 10% solution of caffeine-sodium benzoate under the skin and inside along with acetylsalicylic acid or. contraindicated. With vomiting - intravenous 20 ml of a 40% solution. In case of irritation of the mucous membranes - soda, washing the eyes with a 2% solution. With pronounced changes in the blood, the use of stimulants is recommended [, tezan, (vitamin Bc), cyanocobalamin ()].

Aromatic hydrocarbons are hydrocarbons that contain a cyclic group. The group of aromatic hydrocarbons consists of benzene and its derivatives, aromatic compounds with two benzene rings (biphenyl and its derivatives), hydrocarbons with condensed rings (indene, naphthalene and its derivatives), polynuclear hydrocarbons with condensed rings and their heterocyclic analogs.

Benzene aromatic hydrocarbons are predominantly liquids, partly solids with a characteristic aromatic odor. They are used as solvents, as well as starting products in the synthesis of plastics, synthetic rubber, dyes, varnishes, insecticides, pharmaceuticals and as highly active components of motor fuel. Benzene, toluene, xylene are obtained during the distillation of coal, as well as from oil. Polynuclear aromatic hydrocarbons are found in products of natural origin (oil, petroleum bitumen, etc.), and are also formed during the thermal processing of organic raw materials (dry distillation, cracking, coking and semi-coking).

Vapors of aromatic hydrocarbons in high concentrations have a narcotic and partly convulsive effect. In acute poisoning, death occurs from respiratory arrest. The danger of acute poisoning when using aromatic hydrocarbons is great, especially when working in confined spaces. Even more dangerous are chronic poisonings, which are characterized by severe damage to the blood and blood-forming organs. Individual aromatic hydrocarbons act differently. The most severe chronic poisoning causes benzene (see). In case of poisoning with benzene derivatives, damage to the liver, dysfunction of the nervous system, endocrine organs, especially adrenal glands, and vitamin C metabolism occur. Aromatic hydrocarbons with four methyl groups are mildly irritating. Substances with branched side chains and unsaturated chains have a greater irritant effect, with elongated chains - less.

The toxic properties of aromatic amino and nitro compounds are very high, which is primarily due to their ability to convert oxyhemoglobin into methemoglobin with the occurrence of hypoxemia and hypoxia. Some nitro compounds (trinitrotoluene) are typical liver poisons. Aromatic amino compounds, especially binuclear ones (β-naphthylamine, benzidine, dianisidine), can cause malignant and benign bladder tumors. When hydrogen is replaced by a halogen in the benzene ring, aromatic hydrocarbons acquire narcotic and irritating properties. When hydrogen is replaced by halogen in the side chain, products are formed that are very irritating to the respiratory tract and mucous membranes of the eyes. Their toxicity increases with an increase in the number of halogen atoms in the molecule. Naphthalene and its derivatives affect the nervous system, gastrointestinal tract, kidneys and cause irritation of the upper respiratory tract and skin. The action of all aromatic hydrocarbons is characterized by changes in the blood (erythrocyte hemolysis, the appearance of Heinz bodies, anemia). Under the action of vapors and dust of aromatic hydrocarbons, clouding of the lens is observed. The occurrence of cataracts is associated with a decrease in the content of cysteine ​​in the body during detoxification of the poison. Compounds of polynuclear aromatic hydrocarbons with condensed rings are characterized by carcinogenic activity, which a number of authors directly depend on the content of 3-4-benzpyrene in aromatic hydrocarbons. Tumors usually arise from direct contact with these aromatic hydrocarbons, occasionally and in distant organs.

The current sanitary standards for the design of industrial enterprises (SN 245-63) allow the content of benzene in the air of working premises at a concentration of not more than 20 mg / m 3, toluene - 50 mg / m 3, xylene - 50 mg / m 3, naphthalene - 20 mg / m 3. The presence of carcinogenic compounds in the air of working premises is not allowed. When working with aromatic hydrocarbons, it is necessary to observe the protective measures regulated by the indicated standards, as well as sanitary rules and instructions for individual industries. To prevent chronic poisoning, it is important to conduct preliminary and periodic (once a year) medical examinations of those working with aromatic hydrocarbons. For diagnostic purposes, the determination in the urine of the products of oxidation of aromatic hydrocarbons is used. A number of authors propose the definition of benzene in biosubstrates, as well as toluene oxidation products (benzoic and hippuric acids) as an "exposure test" for judging the concentration of products in the air of working premises. It is important to determine the content of organic sulfates in the urine.

In the case of mild acute poisoning, treatment is usually not required (in case of excitation, bromides, valerian drops are prescribed, rest is recommended). In severe cases, they resort to artificial respiration, the appointment of oxygen or carbogen. In case of circulatory disorders, caffeine is injected under the skin and per os along with acetylsalicylic acid or amidopyrine. Adrenaline is contraindicated. When vomiting - intravenous infusion of 20 g of 40% glucose solution. With irritation of the mucous membranes - soda inhalation; eye rinsing with a 2% solution of baking soda.

Physical properties

Benzene and its closest homologues are colorless liquids with a specific odor. Aromatic hydrocarbons are lighter than water and do not dissolve in it, but they easily dissolve in organic solvents - alcohol, ether, acetone.

Benzene and its homologues are themselves good solvents for many organic substances. All arenas burn with a smoky flame due to the high carbon content of their molecules.

The physical properties of some arenes are presented in the table.

Table. Physical properties of some arenas

Name	Formula	t°.pl., °C	t°.bp., °C
Benzene	C 6 H 6	5,5	80,1
Toluene (methylbenzene)	C 6 H 5 CH 3	95,0	110,6
Ethylbenzene	C 6 H 5 C 2 H 5	95,0	136,2
Xylene (dimethylbenzene)	C 6 H 4 (CH 3) 2
ortho-		25,18	144,41
meta-		47,87	139,10
pair-		13,26	138,35
Propylbenzene	C 6 H 5 (CH 2) 2 CH 3	99,0	159,20
Cumene (isopropylbenzene)	C 6 H 5 CH(CH 3) 2	96,0	152,39
Styrene (vinylbenzene)	C 6 H 5 CH \u003d CH 2	30,6	145,2

Benzene - low-boiling ( tkip= 80.1°C), colorless liquid, insoluble in water

Attention! Benzene - poison, acts on the kidneys, changes the blood formula (with prolonged exposure), can disrupt the structure of chromosomes.

Most aromatic hydrocarbons are life threatening and toxic.

Obtaining arenes (benzene and its homologues)

In the laboratory

1. Fusion of salts of benzoic acid with solid alkalis

C 6 H 5 -COONa + NaOH t → C 6 H 6 + Na 2 CO 3

sodium benzoate

2. Wurtz-Fitting reaction: (here G is halogen)

From 6H 5 -G+2Na + R-G →C 6 H 5 - R + 2 NaG

With 6 H 5 -Cl + 2Na + CH 3 -Cl → C 6 H 5 -CH 3 + 2NaCl

In industry

• isolated from oil and coal by fractional distillation, reforming;
• from coal tar and coke oven gas

1. Dehydrocyclization of alkanes with more than 6 carbon atoms:

C 6 H 14 t , kat→C 6 H 6 + 4H 2

2. Trimerization of acetylene(only for benzene) – R. Zelinsky:

3С 2 H2 600°C, Act. coal→C 6 H 6

3. Dehydrogenation cyclohexane and its homologues:

Soviet Academician Nikolai Dmitrievich Zelinsky established that benzene is formed from cyclohexane (dehydrogenation of cycloalkanes

C 6 H 12 t, cat→C 6 H 6 + 3H 2

C 6 H 11 -CH 3 t , kat→C 6 H 5 -CH 3 + 3H 2

methylcyclohexanetoluene

4. Alkylation of benzene(obtaining homologues of benzene) – r Friedel-Crafts.

C 6 H 6 + C 2 H 5 -Cl t, AlCl3→C 6 H 5 -C 2 H 5 + HCl

chloroethane ethylbenzene

Chemical properties of arenes

I. OXIDATION REACTIONS

1. Combustion (smoky flame):

2C 6 H 6 + 15O 2 t→12CO 2 + 6H 2 O + Q

2. Benzene under normal conditions does not decolorize bromine water and an aqueous solution of potassium permanganate

3. Benzene homologues are oxidized by potassium permanganate (discolor potassium permanganate):

A) in an acidic environment to benzoic acid

Under the action of potassium permanganate and other strong oxidants on the homologues of benzene, the side chains are oxidized. No matter how complex the chain of the substituent is, it is destroyed, with the exception of the a -carbon atom, which is oxidized into a carboxyl group.

Homologues of benzene with one side chain give benzoic acid:

Homologues containing two side chains give dibasic acids:

5C 6 H 5 -C 2 H 5 + 12KMnO 4 + 18H 2 SO 4 → 5C 6 H 5 COOH + 5CO 2 + 6K 2 SO 4 + 12MnSO 4 + 28H 2 O

5C 6 H 5 -CH 3 + 6KMnO 4 + 9H 2 SO 4 → 5C 6 H 5 COOH + 3K 2 SO 4 + 6MnSO 4 + 14H 2 O

Simplified :

C 6 H 5 -CH 3 + 3O KMnO4→C 6 H 5 COOH + H 2 O

B) in neutral and slightly alkaline to salts of benzoic acid

C 6 H 5 -CH 3 + 2KMnO 4 → C 6 H 5 COO K + K OH + 2MnO 2 + H 2 O

II. ADDITION REACTIONS (harder than alkenes)

1. Halogenation

C 6 H 6 + 3Cl 2 h ν → C 6 H 6 Cl 6 (hexachlorocyclohexane - hexachloran)

2. Hydrogenation

C 6 H 6 + 3H 2 t , PtorNi→C 6 H 12 (cyclohexane)

3. Polymerization

III. SUBSTITUTION REACTIONS – ionic mechanism (lighter than alkanes)

1. Halogenation -

a ) benzene

C 6 H 6 + Cl 2 AlCl 3 → C 6 H 5 -Cl + HCl (chlorobenzene)

C 6 H 6 + 6Cl 2 t ,AlCl3→C 6 Cl 6 + 6HCl( hexachlorobenzene)

C 6 H 6 + Br 2 t,FeCl3→ C 6 H 5 -Br + HBr( bromobenzene)

b) benzene homologues upon irradiation or heating

In terms of chemical properties, alkyl radicals are similar to alkanes. Hydrogen atoms in them are replaced by halogens by a free radical mechanism. Therefore, in the absence of a catalyst, heating or UV irradiation leads to a radical substitution reaction in the side chain. The influence of the benzene ring on alkyl substituents leads to the fact that the hydrogen atom is always replaced at the carbon atom directly bonded to the benzene ring (a-carbon atom).

1) C 6 H 5 -CH 3 + Cl 2 h ν → C 6 H 5 -CH 2 -Cl + HCl

c) benzene homologues in the presence of a catalyst

C 6 H 5 -CH 3 + Cl 2 AlCl 3 → (mixture of orta, pair of derivatives) +HCl

2. Nitration (with nitric acid)

C 6 H 6 + HO-NO 2 t, H2SO4→C 6 H 5 -NO 2 + H 2 O

nitrobenzene - smell almond!

C 6 H 5 -CH 3 + 3HO-NO 2 t, H2SO4→ With H 3 -C 6 H 2 (NO 2) 3 + 3H 2 O

2,4,6-trinitrotoluene (tol, trotyl)

The use of benzene and its homologues

Benzene C 6 H 6 is a good solvent. Benzene as an additive improves the quality of motor fuel. It serves as a raw material for the production of many aromatic organic compounds - nitrobenzene C 6 H 5 NO 2 (solvent, aniline is obtained from it), chlorobenzene C 6 H 5 Cl, phenol C 6 H 5 OH, styrene, etc.

Toluene C 6 H 5 -CH 3 - a solvent used in the manufacture of dyes, drugs and explosives (trotyl (tol), or 2,4,6-trinitrotoluene TNT).

Xylene C 6 H 4 (CH 3) 2 . Technical xylene is a mixture of three isomers ( ortho-, meta- and pair-xylenes) - is used as a solvent and starting product for the synthesis of many organic compounds.

Isopropylbenzene C 6 H 5 -CH (CH 3) 2 serves to obtain phenol and acetone.

Chlorine derivatives of benzene used for plant protection. Thus, the product of substitution of H atoms in benzene with chlorine atoms is hexachlorobenzene C 6 Cl 6 - a fungicide; it is used for dry seed dressing of wheat and rye against hard smut. The product of the addition of chlorine to benzene is hexachlorocyclohexane (hexachloran) C 6 H 6 Cl 6 - an insecticide; it is used to control harmful insects. These substances refer to pesticides - chemical means of combating microorganisms, plants and animals.

Styrene C 6 H 5 - CH \u003d CH 2 polymerizes very easily, forming polystyrene, and copolymerizing with butadiene - styrene-butadiene rubbers.

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AROMATICITY(from the Greek. aroma, genus. case aromatos - incense), a concept that characterizes the totality of structural, energetic. sv-in and features reactions. cyclic abilities. structures with a system of conjugated bonds. The term was introduced by F. A. Kekule (1865) to describe St. compounds structurally close to - the ancestor of the class.

Among the most important features of aromaticity belongs to the tendency aromatic. conn. to substitution, which preserves the system of conjugated bonds in the cycle, and not to addition, which destroys this system. In addition to its derivatives, such p-tions are characteristic of polycycle h. aromatic. (eg, and their derivatives), as well as for isoelectronic conjugated heterocyclic. connections. It is known, however, a lot of Comm. (, etc.), to-rye also easily enter into substitution p-tions, but do not have all other features of aromaticity.

reaction ability cannot serve as an accurate characteristic of aromaticity also because it reflects St. Islands not only basic. the state of this compound, but also the transition state (activated complex) of the district, in which it is Comm. enters. Therefore, more stringent criteria for aromaticity are associated with the analysis of physical. St. in the main. electronic states cyclic. related structures. The main difficulty is that aromaticity is not an experimentally determined characteristic. Therefore, there is no unambiguous criterion for establishing the degree of aromaticity, i.e. degree of similarity to St. you. Below are considered naib. important features of aromaticity.

The structure of the electron shell of aromatic systems.

The tendency and its derivatives to preserve the structure of the conjugated ring in decomp. transformations means increased. thermodynamic and kinetic stability of this structural fragment. Stabilization (lowering electronic energy) or having cyclic. structure, is achieved with the complete filling of all binding molecular and vacancies of non-bonding and anti-bonding. The fulfillment of these conditions is achieved when the total number in the cyclic. equals (4n + 2), where n = 0,1,2... (Hückel's rule).

This rule explains the stability (f-la I) and cyclopentadienyl (II; n = 1). It made it possible to correctly predict the stability of cyclopropenyl (III; n = 0) and cycloheptatrienyl (IV; n = 1). In view of the similarity of electron shells Comm. II-IV and they, like the higher cyclic. - , , (V-VII), are considered as aromatic. systems.

Hückel's rule can be extrapolated to a number of conjugated heterocyclic. conn. - derivatives (VIII) and pyrylium (IX), isoelectronic, five-membered heterocycles of type X ( , ), isoelectronic to cyclopentadienyl. These compounds are also classified as aromatic. systems.

For derivatives of compounds II-X and other more complex structures obtained by isoelectronic substitution of methine groups in I-VII, also characterized by high thermodynamic. stability and general tendency to p-tions of substitution in the nucleus.

Cyclic. conjugated, having 4n in the cycle (n = 1.2 ...), are unstable and easily enter into addition p-tions, since they have an open electron shell with partially filled non-bonding ones. Such connections, for example. a typical example of which is cyclobutadiene (XI), include kantiaromatich. systems.

Rules that take into account the number in the cycle are useful for characterizing St. in monocyclic. structures, but are not applicable to polycycles. When assessing the aromaticity of the latter, it is necessary to take into account how the electron shells of each individual cycle correspond to these rules. They should also be used with caution in the case of highly charged cyclic. . Thus, the electron shells of the dication and dianion of cyclobutadiene meet the requirements of Hückel's rule. However, these structures cannot be classified as aromatic, since the dication (n = 0) is not stable in a flat form, which provides cyclic. conjugation, and in bent diagonally; the dianion (n=1) is generally unstable.

Energy criteria for aromaticity. Resonance energy. To determine quantities. measures of aromaticity, characterizing increased. thermodynamic aromatic stability. Comm., the concept of resonance energy (ER), or delocalization energy, was formulated.

The heat of formally containing three is 151 kJ/ more than the heat of three. This value, associated with the ER, can be considered as the energy additionally expended on the destruction of the cyclic. system of conjugated benzene rings, stabilizing this structure. T. arr., ER characterizes the contribution of cyclic. conjugation to (total energy, heat of atomization) compounds.

A number of theoretical methods have been proposed. ER estimates. They differ in arr. the choice of a comparison structure (i.e., a structure in which the cyclic conjugation is broken) with a cyclic. form. The usual approach to calculating the ER is to compare the electron energies of the cyclic. structure and the sum of the energies of all isolated contained in it. However, the calculated t. arr. ER, regardless of the quantum chemical used. method tend to increase with the size of the system. This often contradicts experiments. data on St.-wah aromatic. systems. So, the aromaticity in the series polyacenovbenzene (I), (XII), (XIII), tetracene (XIV) decreases (for example, the tendency to addition increases, the alternation of bond lengths increases), and the ER (given in units = 75 kJ /) increase :

This shortcoming is deprived of the magnitude of the ER, calculated by comparing the electronic energies of the cyclic. structure and similar acyclic. conjugated fullen (M. Dewar, 1969). Calculated t. arr. quantities are usually called ER Dewar (ERD). For example, the ERD (1.013) is calculated by comparing it with 1,3,5-hexatriene, and the ERD of cyclobutadiene is calculated by comparing it = = with 1,3-butadiene.

Connections with positive ERD values ​​are referred to as aromatic, with negative values ​​- to antiaromatic, and with ERD values ​​close to zero - to non-aromatic. Although the values ​​of the ERD vary depending on the quantum-chemical approximations. calculation method, refers. their order practically does not depend on the choice of method. Below are the ERD per one (ERD / e; in units), calculated by the modifications. Hückel:

Naib. ERD / e, that is, naib. aromatic, possesses. The decrease in ERD / e reflects a decrease in aromatic. sv. These data are in good agreement with the prevailing ideas about the manifestations of aromaticity.

Magnetic criteria for aromaticity. Cyclic. conjugation leads to the appearance of a ring current, which causes exaltation of the diamagnet. susceptibility. Since the magnitude of the ring current and exaltation reflect the effectiveness of the cyclic. conjugations, they can. b. used as quantities. measure of aromaticity.

Compounds are aromatic, in which induced diamagnetic electronic ring currents (diatropic systems) are supported. In the case of annulles (n = 0,1,2...) there is a direct proportionality between the strength of the ring current and the magnitude of the ERD. However, for non-alternative (eg,) and heterocyclic. conn. this dependency gets worse. In some cases, the system may. both diatropic and antiaromatic, for example. bicyclodecapentaene.

The presence of inductors. ring current in cyclic. conjugated systems is characteristically manifested in the spectra of proton magn. resonance (PMR), because current creates an anisotropic magnetic field. field that significantly affects the chem. shifts associated with rings. Signals located in ext. aromatic parts. rings are shifted towards the strong field, and signals located on the periphery of the ring - towards the weak field. Yes, internal (form VI) and (VII) appear at -60°C in the PMR spectrum, respectively. at 0.0 and -2.99m. d., and external - at 7.6 and 9.28 ppm.

For antiaromatic annulen systems, on the contrary, are characterized by paramagnetism. ring currents leading to a shift ext. in a strong field (paratropic systems). Yes, chem. shift ext. is only 4.8 ppm.

Structural criteria for aromaticity. The most important structural characteristics are its planarity and complete evenness of bonds. can be considered as aromatic if the lengths of carbon-carbon bonds in it lie in the range of 0.136-0.143 nm, i.e. close to 0.1397 nm for (I). For non-cyclic conjugated polyene structures, the C-C bond lengths are 0.144-0.148 nm, and the C=C bonds are 0.134-0.135 nm. An even greater alternation of bond lengths is characteristic of antiaromatic. structures. This is supported by rigorous non-empirical data. geometric calculations. parameters of cyclobutadiene and experiment. data for its derivatives.

Proposed diff. expressions for quantities. characteristics of aromaticity according to the degree of alternation of bond lengths, for example. for the aromaticity index (HOMA d) is introduced:

where a \u003d 98.89, X r is the length of the r-th bond (in A), n is the number of bonds. For