06 Organic Reactions

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ORGANIC REACTIONS: AN INTRODUCTION Introduction The wide variety of functions and their combination in different skeletal frameworks implies an even wider variety of possible reactions. In fact, most times, different reactions occur simultaneously and it is just the skill in controlling the experimental conditions, what will finally lead to the required products and the yield of the process. Organic reactions constitute a vast jungle of chemical changes, but nevertheless they can be classified using some simple criteria; this allows a high school approach to this fascinating field of chemistry. Attacking Species and Substrates The reactants in a chemical reaction can be further classified. In organic chemistry the substrate is the organic substance that will suffer the change and the attacking species the inorganic agent that is acting on it. In many chemical reactions both reactants are organic; in these cases the substrate is the reactant on which we focus our attention. For instance, when an alcohol and an acid react to form an ester, any of the two can be considered the substrate depending whether we are studying the reactions of acids or the reactions of alcohols. THE CLASSIFICATION OF ORGANIC REACTIONS Organic reactions are classified based in both the nature of the attacking species and the changes that the substrate undergoes. As organic reactions are very frequently multistage processes, they are also classified according to how many species (molecules, ions, etc.) are involved in the rate determining step. A reaction can be thus classified (for instance) as a monomolecular nucleophilic substitution (SN1 type of reaction) or an bimolecular electrophilic addition (AN2 type of reaction). Organic Reactions According to the Attacking Species 

Free Radicals and Homolytic Reactions

According to the nature of the attacking species, organic reactions are said to be homolysis (or free radical) or heterolytic (either nucleophilic or electrophilic).The attacking species can be classified (and accordingly the reactions in which they intervene) as free radicals, nucleophiles and electrophiles. Free radicals are formed if a bond splits evenly - each atom getting one of the two electrons. The name given to this is homolytic fission. Homolytic reactions are frequently triggered by light or peroxides (substances showing -O-O- bonds that easily break homolytically) To show that a species (either an atom or a group of atoms) is a free radical, the symbol is written with a dot attached to show the unpaired electron. For example: a chlorine radical a methyl radical

Cl CH3

2 Free radical attack gives way to what is known as a free radical or better a homolytic reaction. 

Electrophiles and Electrophilic Reactions

An electrophile is something which is attracted to electron-rich regions in other molecules or ions. Because it is attracted to a negative region, an electrophile must be something which carries either a full positive charge, or has a slight positive charge on it somewhere. The electrophile is normally the slightly positive ( +) end of a molecule like hydrogen bromide, HBr. Other frequently found nucleophiles are very unstable species formed in the reacting mixtures. Some examples are shown here.

The NO2+ cation is called the nitronium ion and is the attacking species in the preparation of nitrocompounds (T.N.T. for example). The CH3+ and the CH3CO+ cations are examples of carbocations. These reactive species are not isolated but have been proved to be the active intermediates in many reactions. Metallic cations are not electrophiles because they do not “want” to take any electros. They have already lost them to become stabilised Reactions in which the key stage involves an electrophile are called electrophilic reactions. 

Nucleophiles and Nucleophilic Reactions

A nucleophile is a species (an ion or a molecule) which is strongly attracted to a region of positive charge in something else. Nucleophiles are either fully negative ions, or else have a strongly - charge somewhere on a molecule. Common nucleophiles are hydroxide ions, cyanide ions, water and ammonia.

Notice that each of these contains at least one lone pair of electrons, either on an atom carrying a full negative charge, or on a very electronegative atom carrying a substantial - charge. The negative methyl group is the simplest example of a carbanion. Of course reaction involving nucleophiles are named nucleophilic reactions. Organic Reactions According to the Substrate’s Changes 

Substitution reactions

These are reactions in which one atom in a molecule is replaced by another atom or group of atoms. In these reactions a σ bond is broken and a new σ bond is formed.

3 Simple examples of substitution are the reaction between methane and chlorine in the presence of UV light (or sunlight) and the reaction of a haloalkane with hot water.

Notice that in the first example one of the hydrogen atoms in the methane has been replaced by a chlorine atom and in the second one, bromine has been replaced by a hydroxyl group. That's substitution. 

Addition Reactions

In addition reactions a π bond is broken to form two σ bonds, generally one for each of the two atoms involved in the original π bond. For example, adding hydrogen bromide (HBr) to a double bond in an alkene to form a haloalkane and the addition of hydrogen cyanide (HCN) to an aldehyde to give a 2hydroxi-nitrile

An addition reaction is a reaction in which two molecules join together to make a bigger one. Nothing is lost in the process. All the atoms in the original molecules are found in the bigger one. 

Elimination Reactions

Elimination reactions are formally the reverse of addition reactions: two σ bonds disappear and one π bond is formed instead. Simultaneously a (generally) small molecule is formed. The dehydration of ethanol by the action of hot concentrated sulphuric acid is a typical example. The acid is not written into the equation because it serves as a catalyst. You could eventually write, for example, "conc. H2SO4" over the top of the arrow. 

Condensations and Addition / Elimination Reactions

These two types of reaction are closely related: in fact some times the names are interchanged. In both cases an addition occurs to molecule bearing a C=O grouping and this addition is followed by the elimination of a (generally) small molecule. The difference stands in the way the elimination occurs.

4 When the C=O belongs to either a ketone or an aldehyde, the double bond will be changed generally into a C=C or C=N bond. A double bond (σ/π pair) is changed into a new double bond (σ/π pair) and a water molecule is formed. These reactions are condensation reactions. The reaction of any ketone with hydroxylamine to form an oxime is an example:

The C=O bond has been replaced by a C=N- bond. In case the C=O is part of an ester amide or the so called “acid derivatives” a different route is followed: the original double bond is regenerated and the “other” part of the function is substituted: the result is just a substitution (σ / σ) at an unsaturated carbon (carbon bearing a double bond). These are preferably named addition /eliminations. The acid catalysed formation and hydrolysis of an ester such as ethyl ethanoate belong to this class. These are in fact reversible reactions.

The –OH group (hydroxy) of the acid has been replaced by an –OCH 2CH3 (ethoxy) group. 

Rearrangement Reactions

In rearrangement reactions a C-C bond (mostly) in the chain is broken and part of the chain shifts to a new position . The isomerisation of alkanes is good example. It is used particularly to change straight chains containing 5 or 6 carbon atoms into their branched isomers. For example:

In order to raise the octane rating of the molecules found in petrol (gasoline) and so make the petrol burn better in modern engines, the oil industry rearranges straight chain molecules into their isomers with branched chains. Hydrocarbons used in petrol (gasoline) are given an octane rating which relates to how effectively they perform in the engine. A hydrocarbon with a high octane rating burns more smoothly than one with a low octane rating. Molecules with "straight chains" have a tendency to pre-ignition. When the petrol / air mixture is compressed they tend to explode, and then explode a second time when the spark is passed through them. This double explosion produces knocking in the engine. Octane ratings are based on a scale on which heptane is given a rating of 0, and 2,2,4trimethylpentane a rating of 100. 

Organic Acid / Base reactions

Organic acids behave just like any other acid. Carboxylic acids are generally from weak to very weak although there are some pretty strong acids as trichloro-ethanoic

5 acid and methanoic acid. But there are other acids as the sulphonic acids that are as strong as their inorganic partners. Sulphonic acids belong to this class. They can be considered as derivatives of sulphuric acid in which one of the –OH groups has been replaced by an organic chain

Amines are the bases in organic chemistry. They can be considered as derivatives of ammonia in which one, two or all three hydrogen atoms have been replaced by organic chains. Consequently amines are weak bases although generally slightly stronger than ammonia. The lone pair on the N atom can coordinate to several groups (a Lewis base) most frequently accepting a positive hydrogen ion (a Bronsted base). CH3CH2CH2NH2 Propylamine or 1-aminopropane 

(CH3)2NH Dimethylamine

(CH3)3N Trimethylamine

Organic Red-Ox Reactions

All organic compounds can be burnt to form water and carbon dioxide. Boiling potassium permanganate (manganate(VII)) in acidic or alkaline solution or chromic acid (Chromium (VI) oxide dissolved in sulphuric acid) will completely destroy almost any organic compound turning it into CO2 and H2O too. Obviously in these cases organic compounds behave all as reducing agents. There are many reactions in which hydrogen linked to a carbon atom is replaced by a more electronegative atom (the chlorination of methane for instance) that can be considered from the red-ox point of view. But when organic chemists talk about “oxidation” and “reduction” they generally refer to the old good “gain / loss of oxygen” concept. A carbon atom in an alkane gets oxidised when it is part of the C-OH group (alcohols). Alcohols can be oxidised to aldehydes and ketones (the C atom is bonded twice to oxygen). Further oxidation of aldehydes leads to carboxylic acids. Ketones are broken into two different chains (cleavage of the molecule). Alkenes are readily oxidised and broken down too. There is a vast range of redox reactions in organic chemistry that can include additions, substitutions, eliminations etc. We will not discuss them in this course. Organic Reactions According to the Molecularity of their Rate Determining Step As mentioned before, organic reactions are complex multistage processes. The rate determining step in these reactions may be:  Monomolecular that is, involve just one of the reaction species (e.g. the spontaneous unassisted cleavage of the C-Cl bond in some hydrolyses of haloalkanes).  Bimolecular: two reacting species are involved in the rate determining step (e.g. the addition of bromine to an alkene).

6 The essentials of this classification can be found summarised in the chart at the end of the chapter

SOME SPECIFIC EXAMPLES OF ORGANIC REACTIONS Homolytic Substitution The reaction we are going to explore is the first example of the previous paragraph between methane and chlorine in the presence of ultraviolet light - typically sunlight. This is a good example of a photochemical reaction (a reaction brought about by light). CH4 + Cl2 CH3Cl + HCl The organic product is chloromethane. This is a substitution reaction (sigma bond replaced by sigma bond) and a homolytic or free radical reaction (started by chlorine atoms with an unpaired electron) The mechanism involves a chain reaction. During a chain reaction, for every reactive species you start off with, a new one is generated (it means that a reactant is regenerated in the process) and this keeps the process going. A chain reaction involves three sets of processes or reactions:  Initiation The chain is initiated (started) by UV light breaking a chlorine molecule into free radicals. Cl2 2Cl  Propagation These are the reactions which keep the chain going. CH4 + Cl CH3 + HCl CH3 + Cl2 CH3Cl + Cl  Termination These are reactions which remove free radicals from the system without replacing them by new ones. 2Cl Cl2 CH3 + Cl CH3Cl CH3 + CH3 CH3CH3 It’s worth mentioning that free radical reactions are not necessarily chain reactions although many of them do. It is also important to highlight that a chain reaction is not necessarily an explosive event!. Nuclear chain reactions can lead to devastating explosions because they are triggered by a neutron and in one of the propagation steps three neutrons are formed! That means that for just one neutron to begin with, after three cycles (some milliseconds) you will have 27 neutrons all reacting at the same time! This fact puts the reaction out of any control and the energy is released “all of a sudden”. Electrophilic addition An electrophilic addition reaction is an addition reaction which happens because what we think of as the "important" molecule (the substrate) is attacked by an electrophile.

7 The substrate has a region of high electron density which is attacked by something carrying some degree of positive charge. What follows is a detailed analysis of an electrophilic addition. It is very unlikely that any two different atoms joined together will have the same electronegativity. We are going to assume that Y is more electronegative than X, so that the pair of electrons is pulled slightly towards the Y end of the bond. That means that the X atom carries a slight positive charge. The slightly positive X atom is an electrophile and is attracted to the exposed pi bond in the ethene. Now imagine what happens as they approach each other. You are now much more likely to find the electrons in the half of the pi bond nearest the XY. As the process continues, the two electrons in the pi bond move even further towards the X until a covalent bond is made.

The electrons in the X-Y bond are pushed entirely onto the Y to give a negative Y- ion.

In the final stage of the reaction the electrons in the lone pair on the Y- ion are strongly attracted towards the positive carbon atom. They move towards it and form a co-ordinate (dative covalent) bond between the Y and the carbon. The movements of the various electron pairs are usually shown using curly arrows.

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In the examples to follow we will use this kind of electron shifting diagrams Nucleophilic Substitution: Bimolecular and Monomolecular Reaction Paths If a haloalkane is heated with a solution of sodium or potassium hydroxide, the halogen is replaced by -OH and an alcohol is produced. For example, using bromoethane as a typical primary haloalkane (the Br is attached to the end of the chain forming -CH2-Br) :

The bromine in the haloalkane is simply replaced by an -OH group hence it is a substitution reaction. On the other hand OH- is a nucleophile and the C-Br bond is polarised with the negative end on the Br side rendering the C atom slightly positive. That’s why the reaction is a nucleophilic reaction.

This is an example of a bimolecular nucleophilic substitution. Because the mechanism involves collision between two species in the slow step (in this case, the only step) of the reaction, it is known as an SN2 reaction. We can figure that the OH- anion attacks the substrate from the rear end. During the collision the intrusion of the OH- will strain the molecule to a very unstable situation: 10 electrons around the C atoms, the OH- bond about being formed and simultaneously the Br atom being expulsed with together with the bonding electron pair. This is the transition state, a very unfavourable situation for the system! Finally if the collision is successful, the Br - will be finally expelled and the OH- will be attached to C atom to form an alcohol. Notice that the bonds in the molecule have inverted the configuration turning inside out as an umbrella on a windy day.

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The facts of the reaction are exactly the same as with primary haloalkanes. If the haloalkane is heated under reflux with a solution of sodium or potassium hydroxide in a mixture of ethanol and water, the halogen is replaced by -OH, and an alcohol is produced. For example:

Or if you want the full equation rather than the ionic one:

This mechanism involves an initial ionisation of the haloalkane:

followed by a very rapid attack by the hydroxide ion on the carbocation (carbonium ion) formed:

This is an example of a monomolecular nucleophilic substitution. The difficult step (the ionisation of the covalent haloalkane) only involves one species and is not affected by the presence of the nucleophile. This one will stick to the reactive carbocation as soon as it is available. It is known as an SN1 reaction. Notice that in this case the C atom will be attacked by any of the two sides. The carbocation is planar because of the central atom having just three groups attached to it.

QUESTIONS AND PROBLEMS 1- Classify the following species as free radicals, nucleophiles or electrophiles. State which are formed by homolysis and which by heterolysis. H+ H2O NH3 Cl· OH- Cl+ Na+ CH3CH2+ 2- Wurtz’s reaction was formerly used to prepare hydrocarbons. It consists in the reaction of a haloalkane with metallic sodium as shown below. “R” stands for any possible C chain. Classify this reaction according to what is shown in equation (b).

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3- The following sequence shows the polymerisation of styrene to form the very well known (poly) styrene polymer. a- Classify it according to the different criteria b- Compare it with Wurtz’s reaction. c- Is it a chain reaction? Explain.

4- The equations corresponding to the different steps in the bromination of toluene (a free radical chain reaction) are shown below but jumbled. Write them in the proper sequence and tell which belong to the different stages of a chain reaction. Overall reaction (just for you to see reactants and products)

Jumbled equations (to sequence properly)

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5- The following diagrams show an energy-reaction course profile for an SN1 and an SN2 reaction: which corresponds to which? Explain your choice

6- Inspect the following organic reactions (and classify them (neglect molecularity) a-

b-

12 c-

d-

e-

fgORGANIC REACTIONS

The substrate’s (main organic molecule) point of view

Are classified according to

ADDITION: A π bond is changed into two σ bonds

ELIMINATION: Two σ bonds are changed to one π bond

SUBSTITUTION: σ One σ bond is broken and another σ bond is formed

CONDENSATION: A double bond (σ/π pair) is changed into a new double bond (σ/π pair) and a water molecule is

The attacking species point of view

HOMOLYSIS: reactant splits forming two species with one non-paired electron each A : B → A∙ + B∙ A∙ and B∙ are called FREE RADICALS

HETEROLYSIS: reactant splits asymmetrically forming an anion A:(NUCLEOPHILE)) and a cation B+ (ELECTROPHILE A:B → A:- + B+ (Nitrogen with a lone pair of electrons is also a nucleophile

REARRANGEMENT: A C-C bond in the chain is broken and part of a chain shifts to a new position

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ADDITION / ELIMINATION: A two step substitution on a double bond. Reactant adds and then the double bond is regenerated

ACID / BASE: As studied for inorganic chemistry. Amines are the bases in Org. Chem. but other bases can also react. Acids are either carboxylic

REDOX: As studied in inorganic chemistry. Alkane►Alcohol►Aldehyde►Acid Double bonds can be split

How many species are involved during the rate determining (most difficult) step MONOMOLECULAR BIMOLECULAR