Conformational Analysis of Organic Compounds

Course Topics
Topic 1. Cycloalkanes
Topic 2. Aromatic Hydrocarbons (Arenes)
Topic 3. Halogenated Aromatic Hydrocarbons
Topic 4. Aromatic Aromatic Sulfonic Acids
Topic 5. Aromatic Nitro Compounds
Topic 6. Aromatic Amines
Topic 7. Diazo and azo compounds
Topic 8. Phenols
Topic 9. Aromatic Aldehydes and Ketones
Topic 10. Aromatic Carboxylic Acids and Their Derivatives
Topic 11. Polynuclear Aromatic Compounds
Topic 12. Heterocycles

Cycloalkanes
Topic 1

Outline of the lecture
Cycloalkanes
Naming Cycloalkanes
Conformations of Cycloalkanes
Chemical Properties of Cycloalkanes

Bibliography:
Daley, R., Daley, S. 2012. Organic Chemistry. [online]. [Accessed 7 May 2012]. Available from World Wide Web: www.ochem4free.com
Chernykh, V.P. 2003. Lectures on Organic Chemistry: Tutorial for students of Higher educational institutions. Zolotye stranitsy: Kharkov
Clayden, J., Greeves, N., Warren, S., Wothers, P. 2000. Organic Chemistry. Oxford University Press
Smith, J.G. 2011. Organic Chemistry. McGraw-Hill
Jones, M., Fleming, S.A. 2010. Organic Chemistry. W.W. Norton & Company
Morrison, R.T., Boyd, R.N. 2002. Organic Chemistry. Prentice-Hall of India.
Carey, F.A. 2004. Organic chemistry. MGH.
March, J. 2002. Advanced Organic Chemistry. Wiley: New York
Reutov, O.A., Kurts, A.L., Butin, K.P. 2012. Organic Chemistry: in 4 parts. BINOM Press. Laboratoriya znaniy
Kim, A.M. 2004. Organic Chemistry. Novosibirsk
https://www.masterorganicchemistry.com/2018/01/29/ortho-para-and-meta-directors-in-electrophilic-aromatic-substitution/

Cycloalkanes
Cycloalkanes are hydrocarbons that have the general molecular formula CnH2n and in which some, or all, of the carbon atoms form a ring.

Cycloalkanes
Cycloalkanes are classified according to the cycle size, the number of cycles, and the way the cycles are connected in the molecule.
According to the cycle size there are distinguished:
• cycloalkanes with small cycles (three- and four-membered);
• cycloalkanes with ordinary cycles (five-, six- and seven-membered);
• cycloalkanes with medium cycles (from eight to eleven members);
• macrocycles.
Depending on the number of cycles in the molecule, there are found:
• monocyclic
• bicyclic
• polycyclic cycloalkanes

Naming cycloalkanes
In order to name cycloalkanes, determine the parent name of the compound by counting the number of carbons in the ring as for alkanes and add the prefix cyclo- to the parent name. Further determine the position of the alkyl group or groups on the ring and name them.

Naming cycloalkanes
When a ring has more than one alkyl group attached, number the ring to give the lowest sum of numbers. If the sum of numbers is identical either direction around the ring, then count towards the second group alphabetically on the ring.

Structure and isomerism of cycloalkanes
The structural isomerism of cycloalkanes is determined by the size of the cycle, the nature and mutual arrangement of substituents:
The geometric isomerism of cycloalkanes is due to the different arrangement of substituents relative to the ring plane.

Conformations of cycloalkanes
The molecule of any cycloalkane tends to occupy in space such a form (conformation) in which the sum of angle, torsional and van der Waals strains would be minimal.
With the exception of cyclopropane, the rings of all cycloalkanes are nonplanar. Cyclopropane is planar and destabilized by angle strain and torsional strain. Other molecules of cycloalkanes adopt the shape that minimizes the angle strain.
Angle strain is destabilization that results from distortion of bond angles from their normal values.
Torsional strain is destabilization that results when bonds on adjacent atoms are not staggered.

Stereochemistry of Cycloalkanes
https://en.wikipedia.org/wiki/Bent_bond

Stereochemistry of Cycloalkanes
https://www.dummies.com/education/science/chemistry/how-to-draw-the-chair-conformation-of-cyclohexane/

Stereochemistry of Cycloalkanes

Conformations of cycloalkanes

Conformations of cycloalkanes
The chair conformation of cyclohexane has two distinct types of carbon-hydrogen bonds, namely, axial and equatorial ones. Six of these bonds are axial and the other six are equatorial ones, with one axial and one equatorial bond on each carbon.

Conformations of cycloalkanes
Through a process called ring inversion, or chair-boat-chair interconversion, one chair form of cyclohexane converts to another chair form of cyclohexane. In this process of ring flipping, the equatorial substituents become axial, and the axial substituents become equatorial.

Conformations of cycloalkanes
The process of ring inversion takes cyclohexane through a conformation called the half-chair conformation.

Methods for obtaining cycloalkanes
1. Interaction of α,ω-dihaloalkanes with metallic sodium and zinc. This method is an intramolecular version of the Wurtz reaction, which makes it possible to obtain three-, four-, and five-membered cycloalkanes.
2. Pyrolysis of calcium, barium or thorium salts of dicarboxylic acids. During pyrolysis (dry distillation) of dicarboxylic acids salts, cyclic ketones are formed, which are then reduced to the corresponding cycloalkanes.

Methods for obtaining cycloalkanes
3. Cycloaddition. This is the process of combining two or more unsaturated molecules to form a product of a cyclic structure. For example, dimerization of alkenes ([2+2] cycloaddition) makes it possible to obtain cyclobutane and its homologues.

Methods for obtaining cycloalkanes
4. Electrocyclic reactions. An electrocyclic ring-closing reaction is a reaction in which a σ-bond is formed between the ends of the conjugated system of a molecule.

Chemical Properties of Cycloalkanes
Free radical substitution reactions (SR) are characteristic for cycloalkanes:

Chemical Properties of Cycloalkanes
Hydrogenation
Halogenation

Summary
This lecture considers cycloalkanes, conformations of cycloalkanes as well as their chemical properties.

Questions and Assignments
What are cycloalkanes? Give examples.
Name conformations of cycloalkanes.
What is ring inversion?
Discuss properties of cycloalkanes.
Compare halogenation of cyclopropane and cyclopentane.

Aromatic Hydrocarbons (Arenes)
Topic 2

Outline of the lecture
Aromaticity. Hückel's Rule
Benzene and its Derivatives
Nomenclature and isomerism of benzene derivatives
Chemical Properties of Benzene and its Derivatives

Bibliography:
Daley, R., Daley, S. 2012. Organic Chemistry. [online]. [Accessed 7 May 2012]. Available from World Wide Web: www.ochem4free.com
Chernykh, V.P. 2003. Lectures on Organic Chemistry: Tutorial for students of Higher educational institutions. Zolotye stranitsy: Kharkov
Clayden, J., Greeves, N., Warren, S., Wothers, P. 2000. Organic Chemistry. Oxford University Press
Smith, J.G. 2011. Organic Chemistry. McGraw-Hill
Jones, M., Fleming, S.A. 2010. Organic Chemistry. W.W. Norton & Company
Morrison, R.T., Boyd, R.N. 2002. Organic Chemistry. Prentice-Hall of India.
Carey, F.A. 2004. Organic chemistry. MGH.
March, J. 2002. Advanced Organic Chemistry. Wiley: New York
Reutov, O.A., Kurts, A.L., Butin, K.P. 2012. Organic Chemistry: in 4 parts. BINOM Press. Laboratoriya znaniy
Kim, A.M. 2004. Organic Chemistry. Novosibirsk
https://www.masterorganicchemistry.com/2018/02/02/understanding-ortho-para-meta-directors/

Aromaticity. Hückel's Rule. Benzene and its Derivatives
Aromatic compounds are compounds, which contain cyclic conjugated π-electron systems, that meet the criteria of aromaticity. To be aromatic, a compound must be cyclic and the π electrons must be delocalized over the entire ring. The structure of the compound must be planar, or nearly planar.

Aromaticity. Hückel's Rule
Hückel's rule
Hückel postulated that the number of delocalized π electrons contained in the molecule determined whether or not the molecule was aromatic. He suggested that the number of π electrons needed for aromaticity was 4N + 2 electrons (N is any integer value. N=0, 1, 2, …).

Aromatic ions
A number of cyclic species that bear a positive or negative charge exhibit unusual stability that suggests they are aromatic. These ions meet Hückel's rule, further indicating that they are aromatic.
Because of the unusual stability of the cyclopentadienyl anion, and because these six π electrons meet the criteria for Hückel's rule, the cyclopentadienyl anion is considered to be an aromatic ion.

Benzene and its Derivatives

Benzene and its Derivatives

Benzene and its Derivatives

Benzene and its Derivatives

Nomenclature and isomerism of benzene derivatives
According to the IUPAC nomenclature arenes are considered as derivatives of benzene.
When two substituents are present in a benzene ring, three isomers are possible; they can be distinguished by numbering the atoms of the ring or using the ortho (o), meta (m), and para (p) system.
When a benzene ring is the substituent, use the phenyl group name.

Nomenclature and isomerism of benzene derivatives

Chemical Properties of Benzene and its Derivatives

Chemical Properties of Benzene and its Derivatives
This reaction type is called an electrophilic aromatic substitution. The most important SEAr reactions are nitration, sulfonation, halogenation, alkylation, and acylation.

Chemical Properties of Benzene and its Derivatives

Nitration of benzene
Concentrated nitric acid or a mixture of concentrated nitric and sulfuric acid (nitrating mixture) are often used as nitrating agents.
An electrophilic particle in the nitration reaction is a nitronium ion NO2+, which is formed in the result of the acid-base interaction between nitric and sulfuric acid, where nitric acid is a base.

Nitration of benzene

Sulfonation of benzene
The sulfonation reaction is the reaction of replacing a hydrogen atom on the benzene ring by SO3H. Concentrated sulfuric acid or oleum (sulfur trioxide in sulfuric acid solution) is used for the sulfonation of benzene and its homologues.
The essential difference of the sulfonation reaction from other reactions of electrophilic substitution is its reversibility. Attacking electrophillic particle is sulfur trioxide, SO3.

Sulfonation of benzene

Halogenation of benzene
Substitution of hydrogen atoms on the benzene ring by chlorine or bromine atoms is carried out in the presence of catalysts, which are Lewis acids (AlCl3, FeBr3, ZnCl2 and others). The most common laboratory procedure involves adding the halogen to benzene in the presence of some metallic iron. The iron reacts with the halogen to form a small amount of iron(III) chloride or iron(III) bromide.

Halogenation of benzene
The iron halides are Lewis acids and form complexes with the halogen atoms.
The formation of the bromine-iron (III) bromide complex increases the electrophilicity of the bromine. It can attack the benzene ring and form a σ complex. The next step, in which the FeBr4- ion removes the proton from the σ complex producing bromobenzene, HBr, and FeBr3, is fast.

Halogenation of benzene

Friedel-Crafts alkylation
The mechanism for an alkylation reaction begins as the Lewis acid, in this case AlCl3, reacts with the alkyl halide to form a complex. This complex is the reacting species for a primary alkyl halide. The complex tends to dissociate forming a free carbocation for a tertiary alkyl halide. In addition, if a carbocation-like rearrangement of the alkyl group can occur, it will.
The benzene ring then undergoes electrophilic attack by the complex to form a σ complex – completing the first step of the electrophilic aromatic substitution reaction. Immediately following the first step, the σ complex undergoes the second step and loses a proton to form the alkyl benzene.

Friedel-Crafts alkylation

Friedel-Crafts acylation
A variation of the Friedel-Crafts reaction is the acylation reaction. A Friedel-Crafts acylation reaction involves the reaction of an acyl halide or an acid anhydride and a Lewis acid with benzene to yield an acylbenzene. Acylation reactions need stoichiometric amount of aluminum chloride because the aluminum chloride first forms an acid/base complex with the carbonyl group of the acyl halide.

Friedel-Crafts acylation

Effects of Monosubstituted Arenes on Substitution
All benzene ring substituent groups are either ortho, para directors or meta directors. Each group varies as how it affects the rate of the electrophilic substitution.
In general, ortho, para directors activate the aromatic ring compared to benzene, and meta directors deactivate the ring.

Effects of Monosubstituted Arenes on Substitution
The ortho and para directors are atoms and atomic groups with positive inductive (+I) or positive mesomeric (+M) effects (electron donors):

Effects of Monosubstituted Arenes on Substitution

Effects of Monosubstituted Arenes on Substitution
A methyl group is an electron-donating group, and although it activates all three positions relative to benzene, it activates the ortho and para positions more than the meta positions. This increased reactivity at the ortho and para sites directs the incoming electrophiles primarily to those positions. All alkyl groups are electron-donating ones; thus, they are all ortho and para directing groups.

Effects of Monosubstituted Arenes on Substitution

Effects of Monosubstituted Arenes on Substitution

Effects of Monosubstituted Arenes on Substitution

Effects of Monosubstituted Arenes on Substitution
Ortho and para-directors stabilize the σ complex by their electron-donating properties, and activate a benzene ring in SEAr reactions.
The electrophilic substitution of the corresponding benzene derivatives is faster compared to benzene.
Halogens are ortho, para-directors, but they deactivate the electrophilic substitution reactions, since the following ratio of inductive and mesomeric effects are typical for them: -I > + M.

Effects of Monosubstituted Arenes on Substitution

Effects of Monosubstituted Arenes on Substitution
The meta-directors are atoms or atomic groups with negative inductive (-I) or negative mesomeric effects (-M) (electron-acceptors):

Effects of Monosubstituted Arenes on Substitution
Meta-directors decrease an electronic density in the benzene ring and lower the rate of SEAr reactions compared to a non-substituted benzene:

Effects of Monosubstituted Arenes on Substitution

Effects of Monosubstituted Arenes on Substitution

Multiple substituent effects
When a benzene ring has two or more substituents, all the substituents exert their combined effects on the reactivity of the ring and in the placement of any incoming electrophiles. In most cases, multiple substituents affect an electrophilic aromatic substitution reaction in one of the following four ways.
All available sites are equivalent. This means that a substitution at any one of these sites gives the same product.
All sites have comparable reactivity, but one site is more sterically hindered than the other. The reaction then takes place at the less sterically hindered site.

Multiple substituent effects
The directing effects of the groups reinforce one another. For example, in p-nitrotoluene the nitro group is a meta directing group, the methyl group is an ortho, para directing group, and the two groups are para to each other. Thus, both groups direct to the same pair of carbon atoms as the preferred site of reaction.
The substituents have directing influences that oppose one another. When this occurs, the substituent with the greatest influence controls the outcome of the reaction.

Multiple substituent effects
https://www.masterorganicchemistry.com/2018/03/19/eas-disubstituted-benzenes/

Multiple substituent effects

Multiple substituent effects

Multiple substituent effects

Multiple substituent effects

Multiple substituent effects

Multiple substituent effects

Multiple substituent effects

Quiz Yourself!

Summary
Benzene is very important for the synthesis of dyes, pharmaceuticals and perfumes etc.
Electrophilic substitution reactions provide us with ways of introducing different groups into the benzene ring.
These groups can be modified further and more complex molecules can be synthesized.

Questions and Assignments
What are the aromatic hydrocarbons?
Explain the contemporary understanding of the structure of a benzene molecule.
What are the methods of obtaining aromatic hydrocarbons? Specify the reactions.
Explain the mechanism of aromatic electrophilic substitution.
Write the equations for the reactions of nitration of chlorobenzene, ethylbenzene, and benzenesulfonic acid.
Write the equations of sulfonation reactions of toluene, nitrobenzene, and bromobenzene.

Halogenated Aromatic Hydrocarbons
Topic 3

Outline of the lecture
Aryl Halides
Nucleophilic Substitution on an Aromatic Ring

Bibliography:
Daley, R., Daley, S. 2012. Organic Chemistry. [online]. [Accessed 7 May 2012]. Available from World Wide Web: www.ochem4free.com
Chernykh, V.P. 2003. Lectures on Organic Chemistry: Tutorial for students of Higher educational institutions. Zolotye stranitsy: Kharkov
Clayden, J., Greeves, N., Warren, S., Wothers, P. 2000. Organic Chemistry. Oxford University Press
Smith, J.G. 2011. Organic Chemistry. McGraw-Hill
Jones, M., Fleming, S.A. 2010. Organic Chemistry. W.W. Norton & Company
Morrison, R.T., Boyd, R.N. 2002. Organic Chemistry. Prentice-Hall of India.
Carey, F.A. 2004. Organic chemistry. MGH.
March, J. 2002. Advanced Organic Chemistry. Wiley: New York
Reutov, O.A., Kurts, A.L., Butin, K.P. 2012. Organic Chemistry: in 4 parts. BINOM Press. Laboratoriya znaniy
Kim, A.M. 2004. Organic Chemistry. Novosibirsk

Aryl Halides
An aryl halide is an aromatic compound containing a halogen atom bonded to a benzene ring or other aromatic group.

Nucleophilic Substitution on an Aromatic Ring
Nucleophilic aromatic substitution mechanisms are very diverse, and the type of the mechanism depends on the nature of the aromatic substrate. The most common mechanisms are an addition-elimination mechanism (SNAr) for activated substrates and elimination-addition one for non-activated substrates. Activated substrates contain the strongly electron-withdrawing groups in the ortho or para positions to the halide and non-activated substrates are aryl halides without electron-withdrawing substituents.

The mechanism of addition-elimination (SNAr)
Aryl halides that bear one or more strongly electron-withdrawing groups in the ortho or para positions to the halide readily undergo nucleophilic substitution reactions. These electron-withdrawing groups must be groups that withdraw the electron density due to resonance rather than inductively.

The mechanism of addition-elimination (SNAr)

Benzyne
Aryl halides without electron-withdrawing substituents require extreme conditions or very strong bases for nucleophilic substitution reactions to proceed. For example, under high temperature and pressure, chlorobenzene can be converted into sodium phenoxide when reacted with sodium hydroxide.

Benzyne
The elimination-addition mechanism proceeds via a benzyne intermediate. In this case the substitution takes place not only at the carbon bearing the halide but also at the carbon adjacent to the halide bearing carbon. For example, a 50:50 mixture of 3-methylaniline and 4-methylaniline is formed in the reaction of 4-bromotoluene with sodium amide.

Benzyne
The extra bond in benzyne results from the overlap of sp2 orbitals on adjacent carbon atoms of the ring. The overlap of their bonding orbitals is ineffective. The additional bond is weak and the benzyne is highly unstable and highly reactive.

Nucleophilic Substitution on an Aromatic Ring
After benzyne forms, the amide ion can attack it on either end of its weak, reactive triple bond. This part of the reaction produces a benzene anion. The benzene anion then removes a proton from an ammonia molecule giving the final products, 3-methylaniline and 4-methylaniline.

Summary
In this lecture structure and chemical properties of aryl halides are considered. Mechanisms of nucleophilic substitution on an aromatic ring are discussed.

Questions and Assignments
Discuss structure and reactivity of aryl halides.
What are chemical properties of aryl halides?
Specify mechanisms of aromatic nucleophilic substitution.
Specify the structure of benzyne.

Topic 4
Aromatic Sulfonic Acids

Outline of the lecture
Aromatic sulfonic acids
Mechanism of the sulfonation reaction
Isolation and identification of sulfonic acids
Sulfonation of benzene, its homologues and derivatives
Chemical properties of sulfonic acids

Bibliography:
Daley, R., Daley, S. 2012. Organic Chemistry. [online]. [Accessed 7 May 2012]. Available from World Wide Web: www.ochem4free.com
Chernykh, V.P. 2003. Lectures on Organic Chemistry: Tutorial for students of Higher educational institutions. Zolotye stranitsy: Kharkov
Clayden, J., Greeves, N., Warren, S., Wothers, P. 2000. Organic Chemistry. Oxford University Press
Smith, J.G. 2011. Organic Chemistry. McGraw-Hill
Jones, M., Fleming, S.A. 2010. Organic Chemistry. W.W. Norton & Company
Morrison, R.T., Boyd, R.N. 2002. Organic Chemistry. Prentice-Hall of India.
Carey, F.A. 2004. Organic chemistry. MGH.
March, J. 2002. Advanced Organic Chemistry. Wiley: New York
Reutov, O.A., Kurts, A.L., Butin, K.P. 2012. Organic Chemistry: in 4 parts. BINOM Press. Laboratoriya znaniy
Kim, A.M. 2004. Organic Chemistry. Novosibirsk

Aromatic sulfonic acids
Aromatic sulfonic acids are derivatives of arenes containing the SO3H sulfo group. Aromatic sulfonic acids and their derivatives are used as intermediates for the synthesis of dyes, drugs, detergents, and other practically useful compounds. Nitro, halo, hydroxy and amino compounds can be obtained by substituting the sulfo group.
Aromatic sulfonic acids are obtained by direct sulfonation of hydrocarbons or their derivatives. The most common sulfonating agents are concentrated sulfuric acid and oleum.

Mechanism of the sulfonation reaction
The essential difference of the sulfonation reaction from other reactions of electrophilic substitution is its reversibility. Attacking electrophillic particle is sulfur trioxide, SO3:

Mechanism of the sulfonation reaction
Sulfuric acid with various concentrations, vitriol oil containing ~93% H2SO4, or monohydrate (100% H2SO4) are used as a sulfonating agent. Sulfonation is often carried out with oleum (solution of SO3 in 100% H2SO4).
Chlorosulfonic acid (sulfuric acid monochloride - СlSO3H), sulfuric anhydride, complexed sulfuric anhydride (pyridine sulfotrioxide, dioxane sulfotrioxide) are also used as sulfonating agents.

Mechanism of the sulfonation reaction
As mentioned above, sulfonation with sulfuric acid is a reversible process: the water released dilutes the sulfuric acid and causes a desulfonation reaction.
The equilibrium can be shifted towards the formation of sulfonation products by increasing the amount and concentration of sulfuric acid or by removing water from the reaction medium.

Isolation and identification of sulfonic acids
The isolation of sulfonic acids from the reaction mass containing a large amount of spent sulfuric acid presents significant difficulties.
Most often, sulfonic acids are isolated from the reaction medium in the form of their salts. Soda ash, sodium sulfite, chalk and lime are used as neutralizing agents. Salts of sulfonic acids can be isolated from the solution by evaporation. Salting out with common salt and sodium sulfate is used to isolate salts of sulfonic acids.

Isolation and identification of sulfonic acids
The isolation process of sulfonic acids can be simplified if chlorosulfonic acid is used as a sulfonating agent. In this case, sulfochlorides, are obtained, which are slowly hydrolyzed. Pure sulphonic acid can be obtained by hydrolysis of sulfochlorides. In many cases, sulfochlorides are even more convenient than sulfonic acids or their salts, so it is often preferred to use sulfochlorination instead of sulfonation.

Derivatives of sulfonic acids
Sulfonic acids are compounds difficult to characterize, often do not have certain constants (melting point, boiling point) due to decomposition.
Derivatives of sulfonic acids, namely salts, acid chlorides (sulfochlorides), amides (sulfamides), esters, which have clear melting or boiling points, are used to identify sulfonic acids.
Sulfochlorides are of greatest interest. They are stable compounds, many of which, unlike sulfonic acids, can be distilled.

Derivatives of sulfonic acids
Sulfochlorides can be converted to easily purified amides and other derivatives:
ArSO2Cl + NH3 → ArSO2NH2 + HCl
They are of great independent importance in the production of dyes and in medicine (sulfa drugs, chloramines "B", "T") along with the use for identification purposes.
Esters of sulfonic acids, which are used as alkylating agents, are obtained by acting alcohols or sodium alcoholates on sulfochlorides:
ArSO2Cl + HOC2H5 → ArSO2OC2H5 + HCl

Sulfonation of benzene, its homologues and derivatives
Sulfonation of benzene is carried out with a 2.5-3-fold excess of concentrated sulfuric acid at 80-1000С:
Alkyl substituents facilitate the reaction somewhat. Toluene, for example, is sulfonated with vitriol oil at 100°C, forming mainly p-toluenesulfonic acid with an admixture of ortho and meta isomers.

Sulfonation of benzene, its homologues and derivatives
The proportion of the para-isomer increases with an increase in the volume of the alkyl radical in the benzene cycle, and sulfonation of tert.-butylbenzene occurs mainly in the para-position.

Sulfonation of benzene, its homologues and derivatives
Sulfochlorination of benzene and its homologues with chlorosulfonic acid proceeds under milder conditions than direct sulfonation and is less regioselective.

Sulfonation of benzene, its homologues and derivatives
Sulfonation of phenol with sulfuric acid proceeds with the formation of a mixture ortho- and para-hydroxybenzenesulfonic acids and it is an example of the temperature influence on the direction of the process. Ortho-hydroxybenzenesulfonic acid forms at 200С, para-hydroxybenzenesulfonic acid forms at 1000С, which is due to the reaction reversibility.

Sulfonation of benzene, its homologues and derivatives
The amino group is one of the strongest electron-donating ortho- and para- directors; however, it is protonated in 90-100% sulfuric acid or oleum, while the equilibrium shifts towards the protonated form.

Sulfonation of benzene, its homologues and derivatives
Sulfanilic acid is used in the production of dyes and drugs. The product of sulfochlorination of acetanilide with chlorosulfonic acid (para-acetaminobenzenesulfonic acid chloride) is used in the synthesis of sulfanilamide preparations, diuretics, and antidiabetic agents.

Chemical properties of sulfonic acids
Reactions of the sulfo group.
Substitution reactions of the sulfo group.
Reactions of the benzene ring.

Chemical properties of sulfonic acids
Reactions of the sulfo group
Arenesulfonic acids are strong acids and are often compared in strength to sulfuric acid. They are fully ionized in aqueous solutions.
They are characterized by the following reactions:
a) Formation of stable salts:
ArSO3H + NaOH → ArSO3Na + H2O
ArSO3H + NaCl → ArSO3Na + HCl
b) Formation of acid chlorides (sulfonyl chlorides):
ArSO3Na + PCl5 → ArSO2Cl + POCl3 + NaCl

Chemical properties of sulfonic acids
c) Formation of esters that have electrophilic properties and are good alkylating agents:
ArSO2Cl + С2H5ONa → ArSO2O С2H5 + NaCl
d) Formation of amides (sulfonamides):
ArSO2Cl + 2NH3 → ArSO2 NH2 + NH4Cl
Sulfonamides, being weak NH-acids, react with alkalis:
ArSO2 NH2 + NaOH → ArSO2 N-HNa+ + H2O

Chemical properties of sulfonic acids
Sulfo group substitution reactions
a) hydrolysis of sulfonic acids when heated with dilute sulfuric acid:
b) substitution of the sulfo group with a hydroxyl group when fused with alkali - an industrial method for producing phenols:

Chemical properties of sulfonic acids
c) when salts of sulfonic acids are fused with cyanides, nitriles of carboxylic acids are formed:
Reactions of the benzene ring
Sulfo group, being an electron-withdrawing substituent (it has -I and -M effects), deactivates electrophilic substitution and directs the incoming substituent to the meta position.

Summary
In this lecture chemical properties of aromatic sulfonic acids are considered. Derivatives of aromatic sulfonic acids are discussed.

Questions and Assignments
What are aromatic sulfonic acids?
Discuss mechanism of the sulfonation reaction.
Explain how isolation and identification of sulfonic acids is carried out.
Discuss sulfonation of benzene, its homologues and derivatives.
Sum up chemical properties of sulfonic acids and their derivatives.

Topic 5
Aromatic Nitro Compounds

Outline of the lecture
General Information
Nitro Compounds
Reactions of Nitro Compounds
Reduction in Neutral Medium
Reduction in Basic Medium
Electrophilic Substitution
Nucleophilic Substitution

Bibliography:
Daley, R., Daley, S. 2012. Organic Chemistry. [online]. [Accessed 7 May 2012]. Available from World Wide Web: www.ochem4free.com
Chernykh, V.P. 2003. Lectures on Organic Chemistry: Tutorial for students of Higher educational institutions. Zolotye stranitsy: Kharkov
Clayden, J., Greeves, N., Warren, S., Wothers, P. 2000. Organic Chemistry. Oxford University Press
Smith, J.G. 2011. Organic Chemistry. McGraw-Hill
Jones, M., Fleming, S.A. 2010. Organic Chemistry. W.W. Norton & Company
Morrison, R.T., Boyd, R.N. 2002. Organic Chemistry. Prentice-Hall of India.
Carey, F.A. 2004. Organic chemistry. MGH.
March, J. 2002. Advanced Organic Chemistry. Wiley: New York
Reutov, O.A., Kurts, A.L., Butin, K.P. 2012. Organic Chemistry: in 4 parts. BINOM Press. Laboratoriya znaniy
Kim, A.M. 2004. Organic Chemistry. Novosibirsk

General Information
Nitro compounds are obtained by replacing the H–atom of an hydrocarbon with the –NO2 functional group.
The compounds containing more than one nitro group are often highly explosive and impure. Nitro compounds may be liquids or solids. They are not usually found in nature. They are prepared commercially by nitration of organic compounds.

Nitro Compounds
Nitro compounds are present in the following forms in the nature:
3–Nitropropionic acid found in fungi and plants (Indigofera). Nitropentadecene is a defense compound found in termites.
Chloramphenicol is a rare example of a naturally occurring nitro compound.
2–Nitrophenol is an aggregation pheromone of ticks.

Nitro Compounds

Nitro Compounds
Aromatic nitro compounds are called nitroarenes. The position of nitro group and other substituents if any are indicated by Arabic numerals.

Reactions of Nitro Compounds
Reduction of nitro compounds occurs readily with a variety of reducing agents and such reductions afford a particularly useful synthesis of aromatic amines.
The reduction of a nitro compound to an amine requires six equivalents of reducing agent:

Reactions of Nitro Compounds
One would not expect such a reduction to occur in a single step. Indeed, reduction is stepwise and proceeds through a string of intermediates, which, with strong reducing agents in acid solution, have at most a transient existence. The intermediates formed successively from RNO2 by increments of two equivalents of reducing agent are nitroso compounds, R−N=O, and N-substituted azanols (hydroxylamines), RNHOH:

Reactions of Nitro Compounds
Thus N-aryl-substituted azanols can be obtained directly from the corresponding nitro compounds with zinc and ammonium chloride solution. However, zinc and hydrochloric acid gives the amine:
The difference between these reactions is in the reduction rates associated with the acidity of the solution. Ammonium chloride is a much weaker acid than HCl; the pH of ammonium chloride solutions is around 6.

Reactions of Nitro Compounds
Oxidation of the N-arylazanols under controlled conditions yields nitroso compounds. This reaction is not unlike the oxidation of alcohols to ketones.

Reactions of Nitro Compounds
Reduction of aryl nitro compounds with less-powerful reducing agents, especially in alkaline media, gives what may appear to be a mysterious conglomerate of bimolecular reduction products. All of these substances can be reduced to benzeneamine with tin and hydrochloric acid.

Reactions of Nitro Compounds
An important characteristic of aromatic polynitro compounds is their ability to form “charge-transfer” complexes with aromatic hydrocarbons, especially those that are substituted with alkyl groups.

Electrophilic Substitution

Nucleophilic Substitution

Summary
In this lecture chemical properties of aromatic nitro compounds are considered. Reduction reactions are discussed in detail.

Questions and Assignments

Topic 6
Aromatic Amines

Outline of the lecture
Aromatic Amines
Naming Aromatic Amines
Basicity of Aromatic Amines
Reactions of Aromatic Amines
Amide Formation
Ring Halogenation of Phenylamine
Protection of NH2- Group by Acylation
Synthesis of Dyes
Application of Azo Dyes

Bibliography:
Daley, R., Daley, S. 2012. Organic Chemistry. [online]. [Accessed 7 May 2012]. Available from World Wide Web: www.ochem4free.com
Chernykh, V.P. 2003. Lectures on Organic Chemistry: Tutorial for students of Higher educational institutions. Zolotye stranitsy: Kharkov
Clayden, J., Greeves, N., Warren, S., Wothers, P. 2000. Organic Chemistry. Oxford University Press
Smith, J.G. 2011. Organic Chemistry. McGraw-Hill
Jones, M., Fleming, S.A. 2010. Organic Chemistry. W.W. Norton & Company
Morrison, R.T., Boyd, R.N. 2002. Organic Chemistry. Prentice-Hall of India.
Carey, F.A. 2004. Organic chemistry. MGH.
March, J. 2002. Advanced Organic Chemistry. Wiley: New York
Reutov, O.A., Kurts, A.L., Butin, K.P. 2012. Organic Chemistry: in 4 parts. BINOM Press. Laboratoriya znaniy
Kim, A.M. 2004. Organic Chemistry. Novosibirsk

Aromatic Amines
Aryl-substituted amines are called arylamines. Amines are classified as primary, secondary, and tertiary depending on the degree of substitution at the nitrogen atom.

Naming Aromatic Amines

Basicity of Aromatic Amines
Aromatic amines have the basic character. However, they are weaker than alkyl amines and ammonia. This is mainly due to the conjugation of a lone pair of electrons of a nitrogen atom with π-electron system of the aromatic ring. This makes the lone pair less available for bonding with H+. When aniline is protonated, the resonance stabilization is lost. The difference in energy for the arylamine and its protonated form is higher than that for alkylamines. Being weak bases, arylamines form salts with mineral acids only.

Basicity of Aromatic Amines
Substituted anilines have different basicities depending on the electronic nature of the substituent. Electron donating groups at the para position increase the basicity of aniline. The stronger the electron donor on the ring is, the higher the basicity of the aniline. Similarly, electron-withdrawing groups at the para position decreases the basicity of anilines. Substituents at the meta and ortho positions also exert their influence on the basicity of anilines.

Preparation of Aromatic Amines
Aromatic amines can be synthesized by reduction of the corresponding nitro compound:

Preparation of Aromatic Amines
One molar equivalent of hydrogen sulfide in alcoholic ammonia can be used to reduce one nitro group in the presence of another.

Preparation of Aromatic Amines
The reduction can be accomplished using catalytic hydrogenation or a hydride reducing reagent–NaBH3CN and LiBH3CN are especially effective in reductive aminations.

Reactions of Arylamines
This reaction is called diazotization.

Reactions of Aromatic Amines

Reactions of Arylamines
Replacement Reactions of Arenediazonium Salts - Sandmeyer Reactions
Aryldiazonium salts react readily with various nucleophilic reagents to give a wide variety of aromatic compounds

Reactions of Arylamines
Coupling Reactions of Arenediazonium Salts
Arenediazonium ions react as electrophiles with highly reactive aromatic compounds such as phenol and aromatic tertiary amines. The reaction is called a diazo coupling reaction.

Reactions of Arylamines
Coupling with phenol occurs best in slightly alkaline solution. The alkaline solution produces a phenoxide ion that couples more rapidly, if the solution is too alkaline, a nonreactive diazohydroxide is produced.

Reactions of Arylamines
Phenol and aniline derivatives undergo coupling almost exclusively at the para position unless this position is blocked.
Azocompounds are commonly used as dyes. The azo coupling results in compounds which are highly conjugated. The -SO3-Na+ group is added to the molecule for solubility and to link the dye to the polar fibers of wool, cotton etc.–Orange II is made from 2-naphthol.

Reactions of Arylamines

Reactions of Arylamines
Reactions of Amines with Sulfonyl Chlorides
Primary and secondary amines react with sulfonyl chlorides to produce sulfonamides. A sulfonamide can be hydrolyzed to an amine by heating with aqueous acid.

Reactions of Arylamines
The alkylation reaction. Primary and secondary arylamines react with haloalkanes forming N-alkyl and N, N-dialkylarylamines. The reaction proceeds more difficult due to reduced nucleophilic properties of the nitrogen atom.
The acylation reaction. N-acyl derivatives of aniline and its homologues are called anilides. Amides of carboxylic acids are readily hydrolyzed under acidic or alkaline conditions to form the starting amine and carboxylic acid.
The ability of acyl derivatives to undergo hydrolysis allows applying this reaction in organic synthesis for the temporary protection of the amino group from oxidation and undesirable reactions.

Protection of NH2- Group by Acylation

Reactions of Arylamines
Reaction with aromatic aldehydes
Reactions involving the aromatic ring
Reactions of aromatic electrophilic substitution are typical for arylamines. The amino group exhibits + M effect and acts as a strong electron donor in relation to the benzene ring, thereby activating it in electrophilic substitution reactions. For example, the aniline reacts with bromine water in the absence of a catalyst to form 2,4,6-tribromoaniline immediately.

Amide Formation

Ring Halogenation of Phenylamine

Summary
In this lecture nomenclature, methods of synthesis as well as chemical properties of aromatic nitro compounds are considered. coupling reactions of arenediazonium salts are discussed.

Questions and Assignments

Diazo and azo compounds
Topic 7

Outline of the lecture
Diazonium salts
Preparation of Diazonium Salts
Chemical Properties of Diazonium Salts

Bibliography:
Daley, R., Daley, S. 2012. Organic Chemistry. [online]. [Accessed 7 May 2012]. Available from World Wide Web: www.ochem4free.com
Chernykh, V.P. 2003. Lectures on Organic Chemistry: Tutorial for students of Higher educational institutions. Zolotye stranitsy: Kharkov
Clayden, J., Greeves, N., Warren, S., Wothers, P. 2000. Organic Chemistry. Oxford University Press
Smith, J.G. 2011. Organic Chemistry. McGraw-Hill
Jones, M., Fleming, S.A. 2010. Organic Chemistry. W.W. Norton & Company
Morrison, R.T., Boyd, R.N. 2002. Organic Chemistry. Prentice-Hall of India.
Carey, F.A. 2004. Organic chemistry. MGH.
March, J. 2002. Advanced Organic Chemistry. Wiley: New York
Reutov, O.A., Kurts, A.L., Butin, K.P. 2012. Organic Chemistry: in 4 parts. BINOM Press. Laboratoriya znaniy
Kim, A.M. 2004. Organic Chemistry. Novosibirsk

Diazonium Salts

Diazonium Salts

Preparation of Diazonium Salts
Addition of aqueous solution of NaNO2 to a solution of amine hydrochloride in presence of excess of HCl which is cooled by an ice-bath such that the temperature of the reaction remains below 50C diazotization of primary aromatic amine occurs.

Preparation of Diazonium Salts
If electron withdrawing groups are attached to aromatic nucleus then the aromatic amines are difficult to diazotize because the nucleophilicity of the amino-nitrogen is reduced by the partial withdrawal of the unshared electron pair into the nucleus.

Reactions of Diazonium Salts
The Reaction of Diazonium Salts
Reactions of nucleophiles at nitrogen
Nucleophiles react with diazonium ions to give covalent diazo-compounds. For example, phenol via phenoxide ion couples with diazonium salt at pH 9-10 to afford para-azophenols in good yield.

Reactions of Diazonium Salts
One Electron Reductions
Diazonium ions could be reduced by single electron transfer to give an aryl radical and nitrogen. Copper (I) is frequently used for this purpose and the aryl radical is highly reactive capable of abstracting a ligand from the transition metal ion or a hydrogen atom from a covalent bond.

Reactions of Diazonium Salts
Reactions in which Nitrogen Eliminated
Replacement by Hydroxyl
Diazonium salt on warming in water gives phenol via SN1 mechanism. The reaction is generally performed in acidic solution to preserve phenol in its unionized form.

Reactions of Diazonium Salts
Replacement by Halogen
Schiemann Reaction
Treatment of an aqueous solution of diazonium salt with fluoroboric acid under cold conditions gives diazonium fluoroborate as precipitate, which could be dried and gently heated to afford the flurobenzene by decomposition. The reaction involves SN1 mechanism.

Reactions of Diazonium Salts
Sandmeyer Reaction
This method provides an effective route for the preparation of aromatic bromides and chlorides. Addition of cold aqueous solution of Diazonium chloride to a solution of CuCl in HCl medium gives a sparingly soluble complex which is separated and heated to give aryl chloride or bromide by decomposition.

Reactions of Diazonium Salts
Coupling Reactions
Diazonium ions are weak electrophiles, however, they undergo coupling with activated aromatic nuclei such as aryl amines, phenols and aromatic heterocyclic compounds. For example, N,N-dimethylaniline reacts with diazonium ion almost at the para-position. However, the careful control of the pH of the reaction medium is necessary for the success of the process.

Reactions of Diazonium Salts
In case of primary and secondary aromatic amines, the reaction preferentially takes place at the nitrogen atoms of the diazonium ions. For example, aniline adds to the aromatic diazonium salt to give diazoaminobenzene.

The Synthetic Value of Diazo-Coupling
Dye-stuffs
Aromatic azo-compounds are coloured. Several of those compounds synthesized by the diazo-coupling are employed as dye-stuffs. These compounds can be classified into three groups. First group of azo-compounds are neutral which are used as azoic combination (or ingrain) dyes. An example is para red which is prepared by coupling of 2-napthol with p-nitrobenzenediazonium salt.

The Synthetic Value of Diazo-Coupling

The Synthetic Value of Diazo-Coupling
The second group of azo-compounds posses either a sulfonic acid group or an amino group which are generally adsorbed directly on the fiber from aqueous solution. Examples are orange II (an acidic dye) and Bismarck brown R (a basic dye).

The Synthetic Value of Diazo-Coupling

The Synthetic Value of Diazo-Coupling
Azo-compounds that contain chelating groups to bind with a metal ions such as Al(III) are used a mordant dyes. An example is alizarin yellow R, which contains phenolic and carboxyl chelating groups.

Indicators
Azo-compounds that contain both an acidic and a basic group can be utilized as indicators since the colours of the conjugate acid and the conjugate base are different. Examples are methyl orange and methyl red which are prepared by coupling of dimethylaniline with diazotized sulfanilic acid and diazotized anthranilic acid, respectively.

Indicators

Application of Azo Dyes

Summary

Questions and Assignments

Topic 8
Phenols

Outline of the lecture
Phenols
Naming Phenols
Chemical Properties of Phenols. Acidity
Ester Formation
Ether Formation
Halogenation
Nitration
Sulfonation
Kolbe Reactions

Bibliography:
Daley, R., Daley, S. 2012. Organic Chemistry. [online]. [Accessed 7 May 2012]. Available from World Wide Web: www.ochem4free.com
Chernykh, V.P. 2003. Lectures on Organic Chemistry: Tutorial for students of Higher educational institutions. Zolotye stranitsy: Kharkov
Clayden, J., Greeves, N., Warren, S., Wothers, P. 2000. Organic Chemistry. Oxford University Press
Smith, J.G. 2011. Organic Chemistry. McGraw-Hill
Jones, M., Fleming, S.A. 2010. Organic Chemistry. W.W. Norton & Company
Morrison, R.T., Boyd, R.N. 2002. Organic Chemistry. Prentice-Hall of India.
Carey, F.A. 2004. Organic chemistry. MGH.
March, J. 2002. Advanced Organic Chemistry. Wiley: New York
Reutov, O.A., Kurts, A.L., Butin, K.P. 2012. Organic Chemistry: in 4 parts. BINOM Press. Laboratoriya znaniy
Kim, A.M. 2004. Organic Chemistry. Novosibirsk

Phenols
Phenol is a compound that has a hydroxyl group bonded to one carbon atom in a benzene ring. Each carbon atom in a benzene ring is sp2 hybridized. Although phenol is an alcohol, its properties are quite different from “normal” alcohols. Phenol and similar ring compounds are called aromatic or aryl alcohols.

Naming Phenols
Phenol nomenclature is complicated. Many phenols have common names that are more widely used than the IUPAC names. For example, 2-methylphenol is known as o-cresol, 3-methylphenol is known as m-cresol and 4-methylphenol is known as p-cresol.

Methods of obtaining phenols
Heating of halogenated benzene with an alkali in the presence of a catalyst
The fusion of sodium salts of sulfonic acids with an alkali

Methods of obtaining phenols
The decomposition of the diazonium salt
Oxidation of cumene (the cumene method)

Chemical Properties of Phenols. Acidity
Phenols show appreciable acidity (p K a = 8 −10). For example, phenol reacts with aqueous NaOH as follows.

Chemical properties of phenols
Reactions involving the hydroxyl group and the aromatic ring are characteristic for phenols.

Ester Formation

Ether Formation

Halogenation

Nitration

Sulfonation

Kolbe Reaction

Azo coupling

Summary

Questions and assignments
What are phenols? Give examples.
What are chemical properties of phenols?
Complete the reactions:

Aromatic Aldehydes and Ketones
Topic 9

Outline of the lecture
Aromatic Aldehydes and Ketones
Friedel-Crafts Acylation
Chemical Properties of Aromatic Aldehydes and Ketones
Addition of Hydrogen Cyanide
The Cannizzaro-Tishchenko reaction
The Benzoin Condensation

Bibliography:
Daley, R., Daley, S. 2012. Organic Chemistry. [online]. [Accessed 7 May 2012]. Available from World Wide Web: www.ochem4free.com
Chernykh, V.P. 2003. Lectures on Organic Chemistry: Tutorial for students of Higher educational institutions. Zolotye stranitsy: Kharkov
Clayden, J., Greeves, N., Warren, S., Wothers, P. 2000. Organic Chemistry. Oxford University Press
Smith, J.G. 2011. Organic Chemistry. McGraw-Hill
Jones, M., Fleming, S.A. 2010. Organic Chemistry. W.W. Norton & Company
Morrison, R.T., Boyd, R.N. 2002. Organic Chemistry. Prentice-Hall of India.
Carey, F.A. 2004. Organic chemistry. MGH.
March, J. 2002. Advanced Organic Chemistry. Wiley: New York
Reutov, O.A., Kurts, A.L., Butin, K.P. 2012. Organic Chemistry: in 4 parts. BINOM Press. Laboratoriya znaniy
Kim, A.M. 2004. Organic Chemistry. Novosibirsk

Aromatic Aldehydes and Ketones

Friedel-Crafts Acylation

Chemical Properties of Aromatic Aldehydes and Ketones
Aromatic aldehydes mostly have the same properties as aliphatic aldehydes. However, aromatic aldehydes exhibit a number of specific characteristics.
Aromatic aldehydes do not undergo the aldol condensation.

Addition of Hydrogen Cyanide

The Cannizzaro-Tishchenko reaction

The Benzoin Condensation
Aromatic aldehydes form a condensation product when heated with a cyanide ion dissolved in an alcohol‐water solution. This condensation leads to the formation of α hydroxy ketones.

Summary

Questions and Assignments
In which following reactions aromatic aldehyde is treated with acid anhydride in presence of corresponding salt of the acid to give unsaturated aromatic acid
Options
(a) Wurtz’s reaction
(b) Perkin’s reaction
(c) Friedel-Craft’s reaction
(d) none of these

Aromatic Carboxylic Acids
and Their Derivatives
Topic 10

Outline of the lecture
Aromatic Carboxylic acids
Side Chain Oxidation of Alkylbenzenes
Synthesis of Amides
Reduction Reactions of Aromatic Carboxylic Acids
Synthesis of Acids Chlorides

Bibliography:
Daley, R., Daley, S. 2012. Organic Chemistry. [online]. [Accessed 7 May 2012]. Available from World Wide Web: www.ochem4free.com
Chernykh, V.P. 2003. Lectures on Organic Chemistry: Tutorial for students of Higher educational institutions. Zolotye stranitsy: Kharkov
Clayden, J., Greeves, N., Warren, S., Wothers, P. 2000. Organic Chemistry. Oxford University Press
Smith, J.G. 2011. Organic Chemistry. McGraw-Hill
Jones, M., Fleming, S.A. 2010. Organic Chemistry. W.W. Norton & Company
Morrison, R.T., Boyd, R.N. 2002. Organic Chemistry. Prentice-Hall of India.
Carey, F.A. 2004. Organic chemistry. MGH.
March, J. 2002. Advanced Organic Chemistry. Wiley: New York
Reutov, O.A., Kurts, A.L., Butin, K.P. 2012. Organic Chemistry: in 4 parts. BINOM Press. Laboratoriya znaniy
Kim, A.M. 2004. Organic Chemistry. Novosibirsk

Aromatic Carboxylic Acids
Aromatic carboxylic acids are compounds, in which a carboxyl group is bonded to a benzene ring. Chemical properties of aromatic carboxylic acids are due to the presence of the carboxyl group and the benzene ring.

Aromatic Carboxylic Acids

Methods of synthesis
Oxidation of Alkylbenzenes
Primary and secondary alkyl groups attached to the benzene ring can be oxidised, using alkaline KMnO4, to the carboxyl group.

Methods of synthesis
Carbonation of Grignard Reagents
Grignard reagents (RMgX) react with carbon dioxide to give magnesium carboxylates which on acidification yield carboxylic acids.

Aromatic Carboxylic Acids

Side Chain Oxidation of Alkylbenzenes

Synthesis of Amides

Reduction Reactions of Aromatic Carboxylic Acids

Synthesis of Acids Chlorides

Summary

Questions and Assignments
What are carboxylic acids? Give examples.
Draw a structure of p-aminobenzoic acid.
What are functional derivatives of carboxylic acids? Give examples.
What are chemical properties of carboxylic acids? Give examples of reactions.
What is application of aromatic carboxylic acids?

Polynuclear Aromatic Compounds
Topic 11

Outline of the lecture
Polynuclear Aromatic Compounds
SStructure and Structure and CStructure and Chemical Structure and Chemical PStructure and Chemical Properties of Structure and Chemical Properties of NStructure and Chemical Properties of Naphthalene
Reactions of electrophilic substitution

Bibliography:
Daley, R., Daley, S. 2012. Organic Chemistry. [online]. [Accessed 7 May 2012]. Available from World Wide Web: www.ochem4free.com
Chernykh, V.P. 2003. Lectures on Organic Chemistry: Tutorial for students of Higher educational institutions. Zolotye stranitsy: Kharkov
Clayden, J., Greeves, N., Warren, S., Wothers, P. 2000. Organic Chemistry. Oxford University Press
Smith, J.G. 2011. Organic Chemistry. McGraw-Hill
Jones, M., Fleming, S.A. 2010. Organic Chemistry. W.W. Norton & Company
Morrison, R.T., Boyd, R.N. 2002. Organic Chemistry. Prentice-Hall of India.
Carey, F.A. 2004. Organic chemistry. MGH.
March, J. 2002. Advanced Organic Chemistry. Wiley: New York
Reutov, O.A., Kurts, A.L., Butin, K.P. 2012. Organic Chemistry: in 4 parts. BINOM Press. Laboratoriya znaniy
Kim, A.M. 2004. Organic Chemistry. Novosibirsk

Polynuclear Aromatic Compounds
The class of aromatic compounds includes not only benzene and its derivatives, but also other substances of a diverse structure. The derivatives of naphthalene are of great importance among these compounds.
Naphthalene consists of two condensed benzene rings. Two carbon atoms (9 and 10) are common for two rings.

Structure and Chemical Properties of Naphthalene
The electronic structure of naphthalene is similar to that of benzene. The naphthalene molecule is flat. The dipole moment is zero, but the electron density is not distributed as uniformly as in the benzene molecule. A higher electron density of the α-positions of naphthalene makes them more reactive than the β-positions. The length of bonds in the molecule of naphthalene is different. Naphthalene, like benzene, exhibits the properties of aromatic compounds. It is characterized by reactions of electrophilic substitution, addition, and oxidation reactions.

Reactions of Electrophilic Substitution
Naphthalene is more reactive than benzene in the reactions of electrophilic substitution (nitration, sulfonation, halogenation). α-Substitution products are mainly formed. This is due to the fact that the electron density is higher in the α-position of the naphthalene molecule. When attacking the α-position, σ-complex formed is more stable than σ-complex formed at the attack of the β-position.

Reactions of Electrophilic Substitution

Reactions of Electrophilic Substitution
When attacking α-positions, the delocalization of the positive charge in the σ-complex occurs with the preservation of the aromaticity of one of the benzene rings in possible resonance structures. In the case of the β-position attack, it is possible to preserve the aromaticity of the benzene ring in one case. Consequently, the α-position substitution is more energetically profitable.

Reactions of Electrophilic Substitution
Sulfonation. Concentrated sulfuric acid is used for sulfonation of naphthalene. Depending on the reaction temperature, α - and β-substitution products are obtained. α-Naphthalenesulfonic acid is formed at 80°C and β-naphthalene sulfonic acid is formed at 160°C.
β-Isomer is converted to α-isomer when heated to a temperature of 160°C.

Reactions of Electrophilic Substitution

Reactions of Electrophilic Substitution
Oxidation reactions. Unlike benzene, the naphthalene nucleus is easily oxidized. The nucleus is also oxidized during the oxidation of the naphthalene homologues.
Reduction reaction. The addition of hydrogen occurs to form 1,4-dihydronaphthalene. Then 1,2,3,4-tetrahydronaphthalene is formed. The latter is further hydrogenated at 200°C to form decahydronaphthalene – decalin:

Polynuclear Aromatic Compounds
More complex condensed systems are also known. They are anthracene and phenanthrene. The properties of anthracene and phenanthrene are similar to naphthalene. Naphthalene and anthracene derivatives are of great practical importance in the production of dyes. The phenanthrene nucleus underlies a number of natural substances related to hormones that are regulators of important life processes.

Polynuclear Aromatic Compounds
Benzene rings can be combined with each other in different ways forming other groups of aromatic hydrocarbons.
Derivatives of biphenyl and triphenylmethane are of great importance in the synthesis of dyes.

Questions and Assignments
What are polynuclear aromatic compounds called?
What are examples of polynuclear aromatic compounds?
What are chemical properties of polynuclear aromatic compounds?
Draw a Venn diagram, describing properties of benzene and naphthalene.
Solve problems on polynuclear aromatic compounds.
Review chemical properties of aromatic hydrocarbons. Fill in the Concept map.

Heterocycles
Topic 12

Outline of the lecture
Heterocyclic compounds
Classification of Heterocycles
Pyrrole
Synthesis of Heterocycles
Chemical Properties of Heterocycles

Bibliography:
Daley, R., Daley, S. 2012. Organic Chemistry. [online]. [Accessed 7 May 2012]. Available from World Wide Web: www.ochem4free.com
Chernykh, V.P. 2003. Lectures on Organic Chemistry: Tutorial for students of Higher educational institutions. Zolotye stranitsy: Kharkov
Clayden, J., Greeves, N., Warren, S., Wothers, P. 2000. Organic Chemistry. Oxford University Press
Smith, J.G. 2011. Organic Chemistry. McGraw-Hill
Jones, M., Fleming, S.A. 2010. Organic Chemistry. W.W. Norton & Company
Morrison, R.T., Boyd, R.N. 2002. Organic Chemistry. Prentice-Hall of India.
Carey, F.A. 2004. Organic chemistry. MGH.
March, J. 2002. Advanced Organic Chemistry. Wiley: New York
Reutov, O.A., Kurts, A.L., Butin, K.P. 2012. Organic Chemistry: in 4 parts. BINOM Press. Laboratoriya znaniy
Kim, A.M. 2004. Organic Chemistry. Novosibirsk

Heterocyclic compounds
Heterocyclic compounds are cyclic compounds which contains one/more atoms of other elements along with carbon atoms.
Hetero atoms are those which contains an atom other than carbon such as nitrogen, sulphur, phosphorus etc.

Classification of Heterocycles

Synthesis of Heterocycles

Pyrrole

Pyrrole

Furan

Furan

Thiophene

Chemical Properties of Heterocycles

Chemical Properties of Heterocycles

Chemical Properties of Heterocycles

Reduction and Oxidation Reactions

Six-membered Heterocycles with One Heteroatom

Methods for obtaining pyridine and its derivatives

Chemical Properties

Chemical Properties

Summary