Substances that can rotate the plane of polarization of light passing through them are called optically active. This phenomenon itself is called optical activity. Optically active substances exist in the form of pairs optical antipodes or enantiomers, which differ (ceteris paribus - the same concentration, the same path length of the light beam in the substance) in the sign of rotation of the plane of polarization of light.

Molecules of optically active substances have the property chirality- enantiomers relate to each other as the original and its mirror image (incompatible under any rotation). Most often, for the occurrence of chirality, the presence in the molecule is necessary. chiral carbon atom ( chiral or asymmetric center) - in a state of sp 3 hybridization and having four different substituents:

An equimolar mixture of enantiomers has no optical activity. Such a mixture is called racemic mixture or racemate.

If a molecule contains several chiral centers, it is very difficult to depict it in a projection similar to the previous figure. In this case, use the projection formulas E. Fisher.

The number of stereoisomers in the case of several chiral centers can be determined by the formula 2 n where n is the number of chiral carbon atoms. In the case of aldotetroses, in which there are two chiral centers, there are 4 stereoisomers:

Molecules 1 and 2, 3 and 4 are enantiomers. Molecules 2 and 4, 1 and 3, 2 and 3 are not enantiomers, however, they are stereoisomers.

Stereoisomers that are not enantiomers are called diastereomers.

Diastereomers differ in chemical and physical properties and can be separated by conventional chemical methods.

The number of stereoisomers may be less than 2n if there is mesoforms. The mesoform occurs if the molecule has internal planes of symmetry. For example, tartaric acid has three stereoisomers:

If isomers 1 and 2 are a pair of enantiomers, then 3 and 4 are the same thing - the molecule has an internal symmetry plane, shown by a dotted line. The meso form is essentially an intramolecular racemate. Indeed, the top 3 (above the dotted line) is a mirror image of the bottom. The optical activity of the mesoform does not possess.

Nomenclature of optical isomers

The first substances for which the phenomenon of optical isomerism was discovered and studied were carbohydrates and amino acids. Therefore, it has historically developed so that the stereoisomers of these compounds are determined by belonging to one or another steric series and to erythro-threo isomers. For compounds of other classes, the concept is used absolute chiral center configuration.

Fisher projection formulas

Fisher's formulas are one of the ways to represent the three-dimensional structure of a chiral center on a plane. Let's take a pair of enantiomers and build the Fisher projection for the right molecule:

Let's choose the direction from which we will consider the molecule - it is shown by an arrow:

In this case, the links C-A and C-E are directed towards us, they, in accordance with the rules for writing the Fisher formula, are depicted by a horizontal line. Links C-B and C-D are directed away from us, they are depicted by a vertical line. As a result, the Fisher projection will look like (1):

Currently, both the vertical and horizontal lines are drawn as solid, the carbon atom is not drawn - the intersection of the lines and implies a chiral center, as a result, the projection (2) is generally accepted.

If we consider the same molecule from the other side, then we can get another Fischer projection:

In general, twelve Fischer projections can be drawn for a given molecule. In order to compare the obtained projections with each other, it is necessary to take into account that the Fisher projections allow a number of transformations over themselves.

1. An even number of permutations. By permutation is meant the exchange of places of any two deputies. For example, in the formula 2b, you can first change D and A (the first permutation), and then E and D (which now stands in place of A) - this will be the second permutation, as a result, 2b has been transformed into 2. It is noticeable that this is the same thing.

2. Projection rotation in the drawing plane by 180, 360, 540, etc. degrees:

3. Cyclic permutation: one substitute (any) is left in place, the remaining three are rearranged in a circle - clockwise or counterclockwise. This operation is equivalent to two permutations, but is sometimes more convenient.

1. An odd number of permutations - swap D and E - one permutation, with the help of a mirror depicted by a vertical dotted line, it is easy to verify that these are enantiomers.

2. Rotation in the plane of the drawing by 90, 270, 450, etc. degrees. Rotate 2b 90 o counterclockwise:

In the resulting formula, we will make an even number of permutations - swap B and E, A and D. Comparing 2b and what happened, we observe that this is an enantiomer.

3. Reflection in the mirror or viewing "in the light."

In the standard notation of the Fisher projection, the main chain or cycle is depicted as a vertical line, the numbering of carbon atoms (according to IUPAC) in the chain goes from top to bottom.

Modern ideas about the structure of organic compounds. Fundamentals of stereochemistry of organic compounds. asymmetric carbon atom. Chirality. Fisher projection formulas.

The theory of the chemical structure of A.M. Butlerov

In 1861 A.M. Butlerov proposed a theory of the chemical structure of organic compounds, which consists of the following main provisions.

1) In the molecules of substances, there is a strict sequence of chemical binding of atoms, which is called the chemical structure.

2) The chemical properties of a substance are determined by the nature of the elementary constituents, their quantity and chemical structure.

3) If substances with the same composition and molecular weight have a different structure, then the phenomenon of isomerism occurs.

4) Since only some parts of the molecule change in specific reactions, the study of the structure of the product helps to determine the structure of the original molecule.

5) The chemical nature (reactivity) of individual atoms in a molecule varies depending on the environment, i.e. on what atoms of other elements they are connected to.

Butlerov's theory gives the fundamental possibility of knowing the geometry of a molecule (microscopic properties) through the knowledge of chemical properties (macroscopic properties). The main provisions of the theory of structure retain their significance to this day.

Electronic theories of chemical bonding.

The electronic structure of organic compounds is depicted using Lewis electronic formulas. In them, with the help of dots, the position of all valence electrons is indicated: chemical bond electrons and lone pairs of electrons. It is believed that lone pairs of electrons are part of the outer shell of only one atom, and the electrons involved in the formation of a covalent bond are part of the outer shell of both atoms. For example, in the Lewis formula for carbon tetrachloride below, all atoms have an octet of electrons.

For each atom in the Lewis structure, a formal charge is determined. It is assumed that the atom owns all unshared electrons and half of the electrons of covalent bonds. An excess of electrons belonging to an atom in a molecule compared to a free atom causes a negative charge, and a deficiency causes a positive charge. The sum of the formal charges of all atoms gives the charge of the particle as a whole.

Basic principles of quantum organic chemistry.

Modern theories of covalent bonding are based on the concepts of quantum mechanics. According to the principles of quantum mechanics, the state of an electron in an atom is determined by the wave function, which is called the atomic orbital. The formation of a chemical bond between atoms is considered as a result of the interaction of two orbitals, each of which contains one electron. In this case, the formation of molecular orbitals (MO) occurs. Two atomic orbitals form two molecular orbitals, one of which ( binding) has a lower energy, and the other ( loosening) is a higher energy than the initial AO.

The bonding electrons occupy the lower energy bonding orbital, so the interaction of the orbitals results in an energy gain.

Depending on the type of combined atomic orbitals, different types of MO are formed. The decisive role in this is played by the symmetry and nodal properties of the orbitals. Nuclear s -orbitals have the symmetry of a ball and do not have nodal surfaces passing through the center of the atom. Nuclear p -orbitals have cylindrical symmetry and three states p x , p y and p z . Each p -orbital has a nodal plane passing through the center of the atom and perpendicular, respectively, to the axis x , y or z .

The nodal surface is where the probability of finding an electron is zero and the wave function changes sign. The more nodes, the higher the energy of the orbital. In this way, p -orbital consists of two parts, in which the signs of the wave functions are opposite.

When considering the electronic structure of polyatomic molecules, it is necessary to use such a set of orbitals for which their maximum overlap is achieved. In connection with this, the concept hybridization orbitals. An excited carbon atom contains four unpaired electrons in its outer energy level and is capable of forming four covalent bonds.

Hybrid orbitals are involved in the formation of bonds.

The first valence state - sp 3 -hybridization . As a result of hybridization involving one s and three p orbitals of the carbon atom, four equivalent sp 3 hybrid orbitals are formed, directed to the vertices of the tetrahedron at angles of 109.5 °:

In the sp 3 hybridization state, the carbon atom forms fours- bonds with four substituents and has a tetrahedral configuration with bond angles equal to or close to 109.5 o:

Methane

The second valence state - sp 2 -hybridization . As a result of hybridization involving one s- and two p-orbitals of the carbon atom, three equivalent sp 2 hybrid orbitals are formed, lying in the same plane at angles of 120 °, and the p-orbital not participating in hybridization is located perpendicular to the plane of hybrid orbitals.

In the sp 2 hybridization state, the carbon atom forms threes-bonds due to hybrid orbitals and onep-bond due to the p-orbital not involved in hybridization and has three substituents.

The third valence state of carbon - sp hybridization . As a result of hybridization involving one s- and one p-orbitals, two equivalent sp-hybrid orbitals are formed, lying at an angle of 180 0, and the p-orbitals not participating in hybridization are located perpendicular to the plane of the hybrid orbitals and to each other. In the sp hybridization state, the carbon atom forms twos-bonds due to hybrid orbitals and twop-bonds due to p-orbitals not participating in hybridization and has two substituents:

Acetylene

Fundamentals of stereochemistry.

Stereochemistry is a part of chemistry devoted to the study of the spatial structure of molecules and the influence of this structure on the physical and chemical properties of a substance, on the direction and speed of their reactions.

Conformations (rotational isomerism).

The transition from the simplest organic hydrocarbon, methane, to its closest homologue, ethane, poses problems of spatial structure, for the solution of which it is not enough to know the previously considered parameters. Without changing either the bond angles or the bond lengths, one can imagine many geometric shapes of the ethane molecule, which differ from each other in the mutual rotation of the carbon tetrahedra around the C-C bond connecting them. As a result of this rotation, rotational isomers (conformers) . The energy of various conformers is not the same, but the energy barrier separating the various rotational isomers is small for most organic compounds. Therefore, under normal conditions, as a rule, it is impossible to fix molecules in one strictly defined conformation. Usually, several turning forms that easily pass into each other coexist in equilibrium.

Consider the methods of graphic representation of conformations and their nomenclature. For the ethane molecule, one can foresee the existence of two conformations maximally different in energy. They are shown below as perspective projections (1) ("lumberjacks"), lateral projections (2) and Newman's formulas .

The conformation shown on the left is called obscured . This name is reminiscent of the fact that the hydrogen atoms of both CH 3 groups are opposite each other. The shielded conformation has an increased internal energy and is therefore unfavorable. The conformation shown on the right is called inhibited , implying that the free rotation around the C-C bond "brakes" in this position, i.e. the molecule exists predominantly in this conformation.

As the molecule becomes more complex, the number of possible conformations increases. Yes, for n-butane, six conformations can already be depicted, differing in the mutual arrangement of CH 3 groups, i.e. turning around the central C-C connection. Below, the conformations of n-butane are depicted as Newman projections. The (shielded) conformations depicted on the left are energetically unfavorable, only hindered conformations are realized in practice.

Various eclipsed and hindered conformations of butane differ in energy. Corresponding energies of all conformations formed during rotation around the central C-C bond.

So, conformations are various spatial forms of a molecule that has a certain configuration. Conformers are stereoisomeric structures that correspond to energy minima on the potential energy diagram, are in mobile equilibrium and are capable of interconversion by rotation around simple bonds.

Sometimes the barrier of such transformations becomes high enough to separate stereoisomeric forms (for example, optically active biphenyls). In such cases, one speaks no longer of conformers, but of real-life stereoisomers .

Geometric isomerism.

An important consequence of the rigidity of the double bond (the absence of rotation around it) is the existence geometric isomers . The most common of these are cis, trans isomers compounds of the ethylene series containing unequal substituents on unsaturated atoms. The simplest example is butene-2 ​​isomers.

Geometric isomers have the same chemical structure, differing in the spatial arrangement of atoms, i.e. on configuration . This difference creates a difference in physical (as well as chemical) properties. Geometric isomers, unlike conformers, can be isolated in pure form and exist as individual stable substances. For their mutual transformation, an energy of the order of 125 - 170 kJ / mol is required, which can be imparted by heating or irradiation.

In the simplest cases, the nomenclature of geometric isomers is not difficult: cis- forms are geometric isomers in which the same substituents lie on the same side of the pi bond plane, trance- isomers have the same substituents on opposite sides of the pi bond plane. In more complex cases, apply Z,E-nomenclature . Its main principle: to indicate the configuration indicate cis-(Z, from German Zusammen - together) or trance-(E, from German Entgegen - opposite) location senior deputies with a double bond.

In the Z,E system, substituents with a higher atomic number are considered senior. If the atoms directly bonded to unsaturated carbons are the same, then they go to the "second layer", if necessary, to the "third layer", etc.

3. Optical isomerism (enantiomerism).

Among organic compounds there are substances capable of rotating the plane of polarization of light. This phenomenon is called optical activity, and the corresponding substances are optically active . Optically active substances occur in pairs optical antipodes - isomers, the physical and chemical properties of which are the same under normal conditions, with the exception of one - the sign of the rotation of the polarization plane. (If one of the optical antipodes has, for example, a specific rotation of +20 o, then the other has a specific rotation of -20 o).

projection formulas.

For a conditional image of an asymmetric atom on a plane, use projection formulas of E. Fisher . They are obtained by projecting onto the plane the atoms with which the asymmetric atom is associated. In this case, the asymmetric atom itself, as a rule, is omitted, retaining only the intersecting lines and substituent symbols. To keep in mind the spatial arrangement of substituents, a broken vertical line is often kept in the projection formulas (the upper and lower substituents are removed beyond the plane of the drawing), but this is often not done. left model in the previous figure:

Here are some examples of projection formulas:

(+)-alanine(-)2-butanol(+)-glyceraldehyde

The names of substances are given their signs of rotation. This means, for example, that the levorotatory antipode of butanol-2 has spatial configuration, expressed precisely by the above formula, and its mirror image corresponds to dextrorotatory butanol-2. Configuration Definition optical antipodes is carried out experimentally.

In principle, each optical antipode can be depicted by twelve (!) Different projection formulas - depending on how the model is located when building the projection, from which side we look at it. To standardize projection formulas, certain rules for writing them have been introduced. So, the main function, if it is at the end of the chain, is usually placed at the top, the main chain is depicted vertically.

In order to match "non-standard" written projection formulas, you need to know the following rules for transforming projection formulas. In order to match "non-standard" written projection formulas, you need to know the following rules for transforming projection formulas.

1. Formulas can be rotated in the plane of the drawing by 180 o without changing their stereochemical meaning:

2. Two (or any even number) permutations of substituents on one asymmetric atom do not change the stereochemical meaning of the formula:

3. One (or any odd number) permutations of substituents at the asymmetric center leads to the optical antipode formula:

4. Rotation in the plane of the drawing by 90 o turns the formula into an antipode, unless at the same time the condition for the location of the substituents relative to the plane of the drawing is changed, i.e. do not assume that now the side deputies are behind the plane of the drawing, and the top and bottom ones are in front of it. If you use the formula with a dotted line, then the changed orientation of the dotted line will directly remind you of this:

5. Instead of permutations, projection formulas can be transformed by rotating any three substituents clockwise or counterclockwise; the fourth substituent does not change the position (such an operation is equivalent to two permutations):

6. Projection formulas cannot be derived from the plane of the drawing.

Racemates.

If there is an asymmetric atom in the formula of a substance, this does not mean at all that such a substance will have optical activity. If an asymmetric center arises in the course of an ordinary reaction (substitution in the CH 2 group, addition at a double bond, etc.), then the probability of creating both antipodal configurations is the same. Therefore, despite the asymmetry of each individual molecule, the resulting substance is optically inactive. Such optically inactive modifications, consisting of an equal number of both antipodes, are called racemates.

Other types of optically active substances.

This section lists some other classes of organic compounds that also have optical activity (i.e. exist as pairs of optical antipodes).

The carbon atom does not have a monopoly on the creation of chiral centers in the molecules of organic compounds. The center of chirality can also be atoms of silicon, tin, four-covalent nitrogen in quaternary ammonium salts and oxides of tertiary amines:

In these compounds, the center of asymmetry has a tetrahedral configuration, like the asymmetric carbon atom. However, there are also compounds with a different spatial structure of the chiral center.

pyramidal configuration have chiral centers formed by atoms of trivalent nitrogen, phosphorus, arsenic, antimony, sulfur. In principle, the center of asymmetry can be considered tetrahedral if the unshared electron pair of the heteroatom is taken as the fourth substituent:

Optical activity can also occur without chiral center, due to the chirality of the structure of the entire molecule as a whole ( molecular chirality or molecular asymmetry ). The most typical examples are the presence chiral axis or chiral plane .

The chiral axis arises, for example, in allenes containing various substituents at sp 2-hybrid carbon atoms. It is easy to see that the compounds below are incompatible mirror images, and therefore optical antipodes:

Another class of compounds that have a chiral axis are optically active biphenyls, which have ortho-positions are bulky substituents, which impede free rotation around the C-C bond connecting the benzene nuclei:

Chiral plane characterized by the fact that it can be distinguished "up" and "bottom", as well as "right" and "left" sides. An example of compounds with a chiral plane is an optically active trance- cyclooctene and optically active derivative of ferrocene:

Diastereomerism.

Compounds with several asymmetric atoms have important features that distinguish them from the previously considered simpler optically active substances with one center of asymmetry.

Let us assume that there are two asymmetric atoms in the molecule of a certain substance; let us conventionally denote them A and B. It is easy to see that molecules with the following combinations are possible:

Molecules 1 and 2 are a pair of optical antipodes; the same applies to the pair of molecules 3 and 4. If we compare with each other molecules from different pairs of antipodes - 1 and 3, 1 and 4, 2 and 3, 2 and 4, then we will see that the listed pairs are not optical antipodes: the configuration of one asymmetric atom is the same for them, the configuration of the other is not the same. It's couples diastereomers , i.e. spatial isomers, not constituting optical antipodes with each other.

Diastereomers differ from each other not only in optical rotation, but also in all other physical constants: they have different melting and boiling points, different solubilities, etc. Differences in the properties of diastereomers are often no less than differences in properties between structural isomers.

An example of a compound of the type in question is chloromalic acid.

Its stereoisomeric forms have the following projection formulas:

erythro-forms treo- forms

Titles erythro- and treo- come from the names of carbohydrates erythrose and threose. These names are used to indicate the mutual position of substituents in compounds with two asymmetric atoms: erythro -isomers call those in which two identical lateral substituents are in the standard projection formula on one side (right or left); treo -isomers have the same side substituents on different sides of the projection formula. Two erythro- isomers are a pair of optical antipodes, when mixed, a racemate is formed. A pair of optical isomers are and treo- forms; they also give, when mixed, a racemate that differs in properties from the racemate erythro- forms. Thus, in total there are four optically active isomers of chloromalic acid and two racemates.

With a further increase in the number of asymmetric centers, the number of spatial isomers increases, and each new asymmetric center doubles the number of isomers. It is determined by the formula 2 n , where n is the number of asymmetric centers.

The number of stereoisomers may decrease due to partial symmetry appearing in some structures. An example is tartaric acid, in which the number of individual stereoisomers is reduced to three. Their projection formulas are:

Formula I is identical to formula Ia, as it turns into it when rotated through 180 about in the plane of the drawing and, therefore, does not depict a new stereoisomer. This optically inactive modification is called meso form . Meso- forms are present in all optically active substances with several identical (i.e., associated with the same substituents) asymmetric centers. Projection formulas meso- forms can always be recognized by the fact that they can be divided by a horizontal line into two halves, which are formally identical on paper, but in reality are mirrored:

Formulas II and III depict the optical antipodes of tartaric acid; when they are mixed, an optically inactive racemate, tartaric acid, is formed.

Nomenclature of optical isomers.

The simplest, oldest, but still used system of nomenclature of optical antipodes, is based on a comparison of the projection formula of the called antipode with the projection formula of some standard substance chosen as a "key". Yes, fora-hydroxy acids and a-amino acids, the key is the upper part of their projection formula (in standard notation):

L-hydroxy acids (X = OH) D- hydroxy acids (X = OH)

L-amino acids (X = NH 2) D- amino acids (X = NH 2)

configuration of alla-hydroxy acids having a hydroxyl group on the left in the standard Fischer projection formula are denoted by the sign L; if the hydroxyl is located in the projection formula on the right - sign D

The key to designating the configuration of sugars is glyceraldehyde:

L-(-)-glyceraldehyde D-(+)-glyceraldehyde

In sugar molecules, the designation D- or L- refers to configuration lower asymmetric center.

System D-,L- notation has significant drawbacks: firstly, the notation D- or L- indicates the configuration of only one asymmetric atom, and secondly, for some compounds, different designations are obtained, depending on whether glyceraldehyde or hydroxy acid key is taken as a key, for example:

These shortcomings of the key system limit its current use to three classes of optically active substances: sugars, amino acids, and hydroxy acids. Designed for general use R,S-system Kahn, Ingold and Prelog.

To determine the R- or S-configuration of the optical antipode, it is necessary to arrange a tetrahedron of substituents around an asymmetric carbon atom in such a way that the junior substituent (usually hydrogen) has a direction "from the observer". Then, if the movement during the transition in a circle of the other three deputies from the oldest to the middle in seniority and then to the youngest occurs counterclock-wise - this isS -isomer (associated with the same hand movement when writing the letter S), if clockwise - this is R- isomer (associated with the movement of the hand when writing the letter R).

To determine the seniority of substituents on an asymmetric atom, we use the rules for counting atomic numbers, which we have already considered in connection with the Z, E nomenclature of geometric isomers.

To choose R,S-notations according to the projection formula, it is necessary, by an even number of permutations (which, as we know, do not change the stereochemical meaning of the formula), to arrange the substituents so that the lowest of them (usually hydrogen) is at the bottom of the projection formula. Then the seniority of the remaining three substituents, falling clockwise, corresponds to the designation R, counterclockwise - to the designation S:

5. Methods for obtaining stereoisomers

Obtaining pure stereoisomers is an important task, since, as a rule, only one of the stereoisomeric forms is biologically active. Meanwhile, under normal conditions, as a rule, mixtures of stereoisomers - diastereomers or optical antipodes - are formed. To obtain pure stereoisomeric forms, these mixtures.

For the image on the i-plane of molecules with asymmetric carbon atoms, the projections proposed in 18-1 by E. Fisher are often used.

Consider the principle of their construction using the example of a bromofluorochloromethane molecule. The starting point for constructing Fisheoa projections is the spatial model of the molecule or its wedge-shaped projection.
Let us arrange the molecule in such a way that only the carbon atom of the bromfluorochloromethane molecule remains in the plane of the drawing, as shown in the figure:

Let's project all atoms onto the drawing plane (Br and CL from the bottom up, since they are located under the drawing plane, and F and H - from top to bottom). In order for the resulting projection to differ from the structural formula, we agree not to represent the asymmetric carbon atom. He implied in the Fisher projection at the intersection of the vertical and horizontal lines:

As can be seen from the above example, the Fischer projection is constructed in such a way that the bonds of an asymmetric atom with substituents are depicted by vertical and horizontal (but not oblique!) lines.

When using Fisher projections, it is important to remember that the vertical line in them depicts connections moving away from us, and the horizontal line - connections directed towards us. . This implies the rules for using Fisher projections:

The listed operations with Fisher projections cannot be carried out, since they lead to the projection of the antipode.

Examples.
a) An even number of pairwise permutations. Let's swap the F and CI, Br and H atoms in the bromofluorochloromethane molecule:

b) Circular permutation of three deputies. Let's make a circular permutation of the halogen atoms. The hydrogen atom is left untouched:

When constructing Fischer projection formulas for molecules that include several carbon atoms, the molecule is arranged in such a way that the carbon chain is arranged vertically. Placed at the top most oxidized a carbon atom (as a rule, this atom is part of the carbonyl CH \u003d O or carboxyl COOH groups.):

DL nomenclature

Glyceraldehyde has one center of optical isomerism, since it has one asymmetric carbon atom. Therefore, the aldehyde can exist as two optical isomers.

The right-rotating isomer is designated $D$ by Fischer, and the left-rotating isomer $L$. Carbohydrates obtained from the $D$-isomer of glyceraldehyde were assigned to the $D$-series, and carbohydrates obtained from the $L$-isomer were assigned to the $L$-series.

The $DL$ nomenclature is widely used today to designate the enantiomers of carbohydrates and amino acids. All natural carbohydrates belong to the $D$-series, all natural amino acids belong to the $L$-series.

Fisher projection formulas

In 1891, E. Fisher proposed to represent the spatial structure of compounds in the form of projections.

To create Fisher's projection formulas, the tetrahedron is unfolded in such a way that two bonds located in the horizontal plane are directed towards the observer, and two bonds lying in the vertical plane are located away from the observer.

For example, for $L$-glyceraldehyde, the Fisher projection formula has the form

Since the tetrahedron can be viewed from different angles, one model can represent 12 apparently different Fisher formulas.

Fisher's formulas are projections onto a plane, therefore, when constructing them, the following rules are introduced:

During mutual permutations of two groups in Fisher's formulas, it is possible to transform an enantiomer into its mirror image:

If the chirality of the molecule is related to the plane or axis, then Fischer projections cannot be applied. In such cases, three-dimensional models are used.

Fischer projections for molecules with multiple centers of optical isomerism

The centers of optical isomerism can have a different geometric structure, which can be depicted using the Fisher projection formulas:

There are two potential centers of optical isomerism in the tartaric acid molecule - two carbon atoms to which four different groups are attached.

When constructing a projection formula, a tartaric acid molecule is drawn into a vertical chain. The bonds oriented vertically go beyond the plane of the figure, and those located horizontally are directed towards the observer.

For tartaric acid, the existence of three isomers is possible (the mirror image of the fourth isomer is combined with the third). (+)- and (-)-tartaric acids (A and B, respectively) are enantiomers, that is, optical isomers. They have the same melting point, solubility in water.

The third isomer can be obtained from (+)- or (-)-tartaric acid by reversing one asymmetric center. The result is the meso-form (B), the physical properties of which will differ from those of the enantiomers of tartaric acid.

With respect to (+)- and (-)-tartaric acid, the meso form is a diastereomer.

During the co-crystallization of (+)- and (-)-isomers of tartaric acid in equal amounts, a racemate is formed, which differs from pure isomers in physical and chemical properties.

CHAPTER 7. STEREOCHEMICAL BASIS OF THE STRUCTURE OF ORGANIC COMPOUNDS

Stereochemistry (from the Greek. stereos- spatial) is "chemistry in three dimensions". Most molecules are three-dimensional (threedimentional, abbreviated as 3D). Structural formulas reflect the two-dimensional (2D) structure of the molecule, which includes the number, type, and sequence of binding atoms. Recall that compounds having the same composition but different chemical structure are called structural isomers (see 1.1). A broader concept of the structure of a molecule (sometimes figuratively called molecular architecture), along with the concept of chemical structure, includes stereochemical components - configuration and conformation, reflecting the spatial structure, i.e., the three-dimensionality of the molecule. Molecules that have the same chemical structure may differ in spatial structure, i.e., exist in the form of spatial isomers - stereoisomers.

The spatial structure of molecules is the mutual arrangement of atoms and atomic groups in three-dimensional space.

Stereoisomers are compounds in whose molecules there is the same sequence of chemical bonds of atoms, but a different arrangement of these atoms relative to each other in space.

In turn, stereoisomers can be configuration and conformational isomers, i.e. vary accordingly configuration and conformation.

7.1. Configuration

A configuration is the arrangement of atoms in space without taking into account the differences that arise due to rotation around single bonds.

Configurational isomers can transform into each other by breaking one and forming other chemical bonds and can exist separately as individual compounds. They are divided into two main types - enantiomers and diastereomers.

7.1.1. enantiomers

Enantiomers are stereoisomers that relate to each other as an object and an incompatible mirror image.

Only enantiomers exist as enantiomers. chiral molecules.

Chirality is the property of an object to be incompatible with its mirror image. Chiral (from the Greek. cheir- hand), or asymmetric, the objects are the left and right hand, as well as gloves, boots, etc. These paired objects represent an object and its mirror image (Fig. 7.1, a). Such items cannot be completely combined with each other.

At the same time, there are many objects around us that are compatible with their mirror image, that is, they are achiral(symmetrical), such as plates, spoons, glasses, etc. Achiral objects have at least one symmetry plane, which divides the object into two mirror-identical parts (see Fig. 7.1, b).

Similar relationships are also observed in the world of molecules, i.e. molecules are divided into chiral and achiral. Achiral molecules have planes of symmetry, chiral ones do not.

Chiral molecules have one or more centers of chirality. In organic compounds, the center of chirality is most often asymmetric carbon atom.

Rice. 7.1.Reflection in the mirror of a chiral object (a) and a plane of symmetry cutting the achiral object (b)

Asymmetric is a carbon atom bonded to four different atoms or groups.

When depicting the stereochemical formula of a molecule, the symbol "C" of the asymmetric carbon atom is usually omitted.

To determine whether a molecule is chiral or achiral, it is not necessary to represent it with a stereochemical formula, it is enough to carefully consider all the carbon atoms in it. If there is at least one carbon atom with four different substituents, then this carbon atom is asymmetric and the molecule, with rare exceptions (see 7.1.3), is chiral. So, of the two alcohols - propanol-2 and butanol-2 - the first is achiral (two CH 3 groups at the C-2 atom), and the second is chiral, since in its molecule at the C-2 atom all four substituents are different ( H, OH, CH 3 and C 2 H 5). An asymmetric carbon atom is sometimes marked with an asterisk (C*).

Therefore, the butanol-2 molecule is able to exist as a pair of enantiomers that do not combine in space (Fig. 7.2).

Rice. 7.2.Enantiomers of chiral molecules of butanol-2 do not combine

Properties of enantiomers. Enantiomers have the same chemical and physical properties (melting and boiling points, density, solubility, etc.), but exhibit different optical activity, i.e., the ability to deflect the plane of polarized light*.

When such light passes through a solution of one of the enantiomers, the plane of polarization deviates to the left, the other - to the right by the same angle α. The value of the angle α reduced to standard conditions is the constant of the optically active substance and is called specific rotation[α]. Left rotation is denoted by a minus sign (-), right rotation is indicated by a plus sign (+), and enantiomers are called left and right rotation, respectively.

Other names of enantiomers are associated with the manifestation of optical activity - optical isomers or optical antipodes.

Each chiral compound can also have a third, optically inactive form - racemate. For crystalline substances, this is usually not just a mechanical mixture of crystals of two enantiomers, but a new molecular structure formed by the enantiomers. Racemates are optically inactive because the left rotation of one enantiomer is compensated by the right rotation of an equal amount of the other. In this case, a plus-minus sign (?) is sometimes placed before the name of the connection.

7.1.2. Relative and absolute configurations

Fisher projection formulas. Stereochemical formulas can be used to depict configurational isomers on a plane. However, it is more convenient to use simpler Fisher projection formulas(easier - Fisher projections). Let us consider their construction using lactic (2-hydroxypropanoic) acid as an example.

The tetrahedral model of one of the enantiomers (Fig. 7.3) is placed in space so that the chain of carbon atoms is in a vertical position, and the carboxyl group is on top. Bonds with non-carbon substituents (H and OH) at the chiral center should

* See tutorial for details Remizov A.N., Maksina A.G., Potapenko A.Ya. Medical and biological physics. 4th ed., revised. and additional - M.: Bustard, 2003.- S. 365-375.

Rice. 7.3.Construction of the Fischer projection formula of (+)-lactic acid

us to be directed towards the observer. After that, the model is projected onto a plane. In this case, the symbol of the asymmetric atom is omitted; it is understood as the point of intersection of the vertical and horizontal lines.

The tetrahedral model of a chiral molecule before projection can be placed in space in different ways, not only as shown in Fig. 7.3. It is only necessary that the links that form a horizontal line on the projection be directed towards the observer, and the vertical links - beyond the plane of the picture.

The projections obtained in this way can, with the help of simple transformations, be brought to a standard form in which the carbon chain is located vertically, and the senior group (in lactic acid this is COOH) is on top. Transformations allow two operations:

In the projection formula, it is allowed to interchange any two substituents at the same chiral center an even number of times (two permutations are enough);

The projection formula can be rotated in the plane of the figure by 180? (which is equivalent to two permutations), but not by 90?.

D.L-Configuration designation system. At the beginning of the twentieth century. a classification system for enantiomers was proposed for relatively simple (in terms of stereoisomerism) molecules, such as α-amino acids, α-hydroxy acids, and the like. Per configuration standard glyceraldehyde was taken. Its levorotatory enantiomer was arbitrarily formula (I) is assigned. This configuration of the carbon atom was designated by the letter l (from lat. laevus- left). The dextrorotatory enantiomer was accordingly assigned the formula (II), and the configuration was denoted by the letter d (from Lat. dexter- right).

Note that in the standard projection formula l -glyceraldehyde group OH is on the left, and at d -glyceraldehyde - on the right.

Assignment to d- or l - a number of other structurally related optically active compounds is produced by comparing the configuration of their asymmetric atom with the configuration d- or l -glyceraldehyde. For example, in one of the enantiomers of lactic acid (I) in the projection formula, the OH group is on the left, as in l -glyceraldehyde, so the enantiomer (I) is referred to as l -row. For the same reasons, the enantiomer (II) is assigned to d -row. Thus, from a comparison of the Fisher projections, we determine relative configuration.

It should be noted that l -glyceraldehyde has a left rotation, and l -lactic acid - right (and this is not an isolated case). Moreover, the same substance can be both left-handed and right-handed, depending on the determination conditions (different solvents, temperature).

The sign of the rotation of the plane of polarized light is not related to belonging to d- or l -stereochemical series.

The practical determination of the relative configuration of optically active compounds is carried out using chemical reactions: either the test substance is converted into glyceraldehyde (or another substance with a known relative configuration), or, conversely, from d- or l -glyceraldehyde, the test substance is obtained. Of course, in the course of all these reactions, the configuration of the asymmetric carbon atom should not change.

Arbitrary assignment of conditional configurations to left- and right-handed glyceraldehyde was a forced step. At that time, the absolute configuration was not known for any chiral compound. The establishment of the absolute configuration became possible only thanks to the development of physicochemical methods, especially X-ray diffraction analysis, with the help of which in 1951 the absolute configuration of a chiral molecule was determined for the first time - it was a salt of (+)-tartaric acid. After that, it became clear that the absolute configuration of d- and l-glyceraldehydes is indeed the same as was originally attributed to them.

d,l-System is currently used for α-amino acids, hydroxy acids and (with some additions) for carbohydrates

(see 11.1.1).

R,S-Configuration designation system. The d,L-System is of very limited use, since it is often impossible to assign the configuration of any compound to glyceraldehyde. The universal system for designating the configuration of centers of chirality is the R,S-system (from lat. rectus- straight, sinister- left). It is based on sequence rule, based on the seniority of the substituents associated with the center of chirality.

The seniority of the substituents is determined by the atomic number of the element directly associated with the center of chirality - the larger it is, the older the substituent.

Thus, the OH group is older than NH 2, which, in turn, is older than any alkyl group and even COOH, since in the latter a carbon atom is bonded to the asymmetric center. If the atomic numbers turn out to be the same, the group is considered to be the eldest, in which the atom following the carbon has a higher serial number, and if this atom (usually oxygen) is double bonded, it is counted twice. As a result, the following groups are arranged in descending order of precedence: -COOH > -CH=O > -CH 2 OH.

To determine the configuration, the tetrahedral model of the compound is placed in space so that the smallest substituent (in most cases, this is a hydrogen atom) is the furthest away from the observer. If the seniority of the other three substituents decreases clockwise, then the R-configuration is assigned to the center of chirality (Fig. 7.4, a), if counterclockwise - S- configuration (see Fig. 7.4, b), as seen by the driver behind the wheel (see Fig. 7.4, in).

Rice. 7.4.Determination of the configuration of enantiomers of lactic acid by R,S- system (explanation in text)

Fisher projections can be used to designate a configuration according to the RS-system. To do this, the projection is transformed so that the junior deputy is located on one of the vertical links, which corresponds to its position behind the plane of the drawing. If, after the projection transformation, the seniority of the remaining three substituents decreases clockwise, then the asymmetric atom has the R-configuration, and vice versa. The use of this method is shown on the example of l-lactic acid (numbers indicate the seniority of the groups).

There is an easier way to determine the R- or S-configuration according to the Fisher projection, in which the junior substituent (usually an H atom) is located on one of horizontal connections. In this case, the above permutations are not carried out, but the seniority of the substituents is immediately determined. However, since the H atom is “out of place” (which is equivalent to the opposite configuration), a drop in precedence will now mean not an R-configuration, but an S-configuration. This method is shown on the example of l-malic acid.

This method is especially convenient for molecules containing several chiral centers, when permutations would be required to determine the configuration of each of them.

There is no correlation between the d,l and RS systems: these are two different approaches to designating the configuration of chiral centers. If in the d,L-system, compounds similar in configuration form stereochemical series, then in the RS-system, chiral centers in compounds, for example, of the l-series, can have both R- and S-configurations.

7.1.3. diastereomerism

Diastereomers are called stereoisomers that are not related to each other, like an object and an incompatible mirror image, that is, not being enantiomers.

The most important groups of diastereomers are σ-diastereomers and π-diastereomers.

σ -Diastereomers. Many biologically important substances contain more than one center of chirality in the molecule. In this case, the number of configurational isomers increases, which is defined as 2 n , where n is the number of centers of chirality. For example, in the presence of two asymmetric atoms, the compound can exist as four stereoisomers (2 2 = 4) that make up two pairs of enantiomers.

2-Amino-3-hydroxybutanoic acid has two centers of chirality (C-2 and C-3 atoms) and therefore must exist as four configurational isomers, one of which is a natural amino acid.

Structures (I) and (II), corresponding to l- and d-threonine, as well as (III) and (IV), corresponding to l- and d-allotreonine (from the Greek. alios- the other), relate to each other as an object and an incompatible mirror image, i.e. they are pairs of enantiomers. Comparison of structures (I) and (III), (I) and (IV), (II) and (III), (II) and (IV) shows that in these pairs of compounds, one asymmetric center has the same configuration, while the other is the opposite. These pairs of stereoisomers are diastereomers. Such isomers are called σ-diastereomers, since the substituents in them are linked to the center of chirality by σ-bonds.

Amino acids and hydroxy acids with two centers of chirality are classified as d- or l -series according to the configuration of the asymmetric atom with the smallest number.

Diastereomers, unlike enantiomers, differ in physical and chemical properties. For example, l-threonine, which is part of proteins, and l-allotreonine have different values ​​of specific rotation (as shown above).

Meso compounds. Sometimes a molecule contains two or more asymmetric centers, but the molecule as a whole remains symmetrical. An example of such compounds is one of the stereoisomers of tartaric (2,3-dihydroxybutanedioic) acid.

Theoretically, this acid, which has two centers of chirality, could exist in the form of four stereoisomers (I)-(IV).

Structures (I) and (II) correspond to the enantiomers of the d- and l-series (the assignment was made according to the "upper" center of chirality). It might seem that structures (III) and (IV) also correspond to a pair of enantiomers. In fact, these are formulas of the same compound - optically inactive mesotartaric acid. It is easy to verify the identity of formulas (III) and (IV) by turning formula (IV) by 180? without taking it out of the plane. Despite the two centers of chirality, the mesotartaric acid molecule as a whole is achiral, since it has a symmetry plane passing through the middle of the C-2-C-3 bond. With respect to d- and l-tartaric acids, mesotartaric acid is a diastereomer.

Thus, there are three (not four) stereoisomers of tartaric acids, not counting the racemic form.

When using the R,S system, there are no difficulties in describing the stereochemistry of compounds with several chiral centers. To do this, determine the configuration of each center according to the R,S-system and indicate it (in brackets with the corresponding locants) before the full name. Thus, d-tartaric acid will receive the systematic name (2R,3R)-2,3-dihydroxybutanedioic acid, and mesotartaric acid will have the stereochemical symbols (2R,3S)-.

Like mesotartaric acid, there is a mesoform of the α-amino acid cystine. With two centers of chirality, the number of stereoisomers of cystine is three due to the fact that the molecule is internally symmetrical.

π -Diastereomers. These include configurational isomers containing a π-bond. This type of isomerism is typical, in particular, for alkenes. With respect to the π-bond plane, the same substituents on two carbon atoms can be located one at a time (cis) or at different (trance) sides. In this regard, there are stereoisomers known as cis- and trance-isomers, as shown in the case of cis- and trans-butenes (see 3.2.2). π-Diastereomers are the simplest unsaturated dicarboxylic acids - maleic and fumaric.

Maleic acid is thermodynamically less stable cis-isomer compared to trance-isomer - fumaric acid. Under the action of certain substances or ultraviolet rays, an equilibrium is established between both acids; when heated (~150 ?C), it is shifted towards a more stable trance-isomer.

7.2. Conformations

Around a simple C-C bond, free rotation is possible, as a result of which the molecule can take various forms in space. This can be seen in the stereochemical formulas of ethane (I) and (II), where the CH groups marked in color 3 located differently relative to another CH group 3.

Rotation of one CH group 3 relative to the other occurs without breaking the configuration - only the relative position in space of hydrogen atoms changes.

The geometric shapes of the molecule, passing into each other by rotation around σ-bonds, are called conformations.

According to this conformational isomers are stereoisomers, the difference between which is caused by the rotation of individual sections of the molecule around σ-bonds.

Conformational isomers usually cannot be isolated in an individual state. The transition of different conformations of the molecule into each other occurs without breaking bonds.

7.2.1. Conformations of acyclic compounds

The simplest compound with a C-C bond is ethane; consider two of its many conformations. In one of them (Fig. 7.5, a) the distance between the hydrogen atoms of two CH groups 3 the smallest, so the C-H bonds that are opposite each other repel each other. This leads to an increase in the energy of the molecule and, consequently, to a lower stability of this conformation. When looking along the C-C bond, it is seen that the three C-H bonds at each carbon atom “overshadow” each other in pairs. This conformation is called obscured.

Rice. 7.5.obscured (a, b) and inhibited (in, G) ethane conformations

In another conformation of ethane, which occurs upon rotation of one of the CH groups 3 at 60? (see Fig. 7.5, c), the hydrogen atoms of the two methyl groups are as far apart as possible. In this case, the repulsion of the electrons of the C-H bonds will be minimal, and the energy of such a conformation will also be minimal. This more stable conformation is called inhibited. The difference in the energy of both conformations is small and amounts to ~12 kJ/mol; it defines the so-called energy barrier of rotation.

Newman's projection formulas. These formulas (more simply, Newman projections) are used to depict conformations on a plane. To construct a projection, the molecule is viewed from the side of one of the carbon atoms along its bond with the neighboring carbon atom, around which rotation takes place. When projecting, three bonds from the carbon atom closest to the observer to hydrogen atoms (or, in the general case, to other substituents) are arranged in the form of a three-beam star with angles of 120?. The (invisible) carbon atom removed from the observer is depicted as a circle, from which it is also at an angle of 120? three connections go. Newman projections also give a visual representation of the eclipsed (see Fig. 7.5, b) and hindered (see Fig. 7.5, d) conformations.

Under normal conditions, ethane conformations easily transform into each other, and one can speak of a statistical set of different conformations that differ insignificantly in energy. It is impossible to single out even a more stable conformation in an individual form.

In more complex molecules, the replacement of hydrogen atoms at neighboring carbon atoms with other atoms or groups leads to their mutual repulsion, which affects the increase in potential energy. So, in the butane molecule, the eclipsed conformation will be the least favorable, and the hindered conformation with the most distant CH 3 groups will be the most advantageous. The difference between the energies of these conformations is ~25 kJ/mol.

As the carbon chain lengthens in alkanes, the number of conformations rapidly increases as a result of the expansion of the possibilities of rotation around each C-C bond, so the long carbon chains of alkanes can take many different forms, for example, zigzag (I), irregular (II) and pincer (III ).

A zigzag conformation is preferred, in which all C-C bonds in the Newman projection form an angle of 180°, as in the staggered conformation of butane. For example, fragments of long-chain palmitic C 15 H 31 COOH and stearic C 17 H 35 COOH acids in a zigzag conformation (Fig. 7.6) are part of the lipids of cell membranes.

Rice. 7.6.Skeletal formula (a) and molecular model (b) of stearic acid

In the pincer conformation (III), carbon atoms that are distant from each other in other conformations approach each other. If functional groups, such as X and Y, are at a sufficiently close distance, capable of reacting with each other, then as a result of an intramolecular reaction this will lead to the formation of a cyclic product. Such reactions are quite widespread, which is associated with the advantage of the formation of thermodynamically stable five- and six-membered rings.

7.2.2. Conformations of six-membered rings

The cyclohexane molecule is not a flat hexagon, since with a flat structure the bond angles between carbon atoms would be 120°, i.e., they would significantly deviate from the normal bond angle of 109.5°, and all hydrogen atoms were in an unfavorable eclipsed position. This would lead to cycle instability. In fact, the six-membered cycle is the most stable of all cycles.

The various conformations of cyclohexane result from partial rotation around σ bonds between carbon atoms. Of several non-planar conformations, the most energetically favorable is the conformation armchairs(Fig. 7.7), since in it all the bond angles between the C-C bonds are equal to ~ 110?, and the hydrogen atoms at neighboring carbon atoms do not obscure each other.

In a non-planar molecule, one can only conditionally speak of the arrangement of hydrogen atoms "above and below the plane." Instead, other terms are used: bonds directed along the vertical axis of symmetry of the cycle (in Fig. 7.7, a shown in color), called axial(a), and bonds oriented from the cycle (as if along the equator, by analogy with the globe) are called equatorial(e).

In the presence of a substituent in the ring, the conformation with the equatorial position of the substituent is more favorable, such as, for example, conformation (I) of methylcyclohexane (Fig. 7.8).

The reason for the lower stability of conformation (II) with the axial arrangement of the methyl group is 1,3-diaxial repulsion CH groups 3 and H atoms in positions 3 and 5. In this

Rice. 7.7.Cyclohexane in chair conformation:

a- skeletal formula; b- ball-and-stick model

Rice. 7.8.Cycle inversion of a methylcyclohexane molecule (not all hydrogens shown)

case, the cycle is subjected to the so-called inversions, adopting a more stable conformation. The repulsion is especially strong in cyclohexane derivatives having positions 1 and 3 of the bulk groups.

In nature, there are many derivatives of the cyclohexane series, among which six-hydric alcohols play an important role - inositols. Due to the presence of asymmetric centers in their molecules, inositols exist in the form of several stereoisomers, of which the most common is myoinositis. The myoinositol molecule has a stable chair conformation in which five of the six OH groups are in equatorial positions.