Reaction Mechanisms

Eastern Visayas State University Tacloban City

__________________________________

A “what you’ve learned” Folio Presented to:

Engr. Asuncion Raquel Taboso Chem 225 Instructor __________________________________

As a Final Requirement in Organic Chemistry __________________________________

Presented by:

Jaime B. Peleño, Jr. BSChE 2A

October 2015

The mechanism of a reaction shows the path or steps by which the reaction takes place. It is determined by the experimentally determined rate law or by kinetics of the reaction. The way that this is done is to propose several possible mechanisms that could possibly take stepsplace. In doing this, each proposed mechanism must be consistent with the known properties of the substance involved. Also the total of all the steps included in any proposed mechanism must agree with the known, overall reaction.

Based on the types of molecules involved and the reaction mechanism involved, organic reactions are classified mainly classified to six different types. They are: 1) Addition reactions An organic reaction in which two small organic molecules are combined to form a saturated organic molecule. C2H4(Ethene) + H2 (Hydrogen) –> C2H6 (Ethane)

2) Elimination reactions An organic reaction in which a small molecule is eliminated form organic molecule to form unsaturated molecule. C2H6 (Ethane) –> C2H4(Ethene) + H2 (Hydrogen)

3) Substitution reactions An organic reaction in which a group or an atom present in the reactant is substituted by another same type of group or an atom to form the substituted product. C2H5 Br (Ethyl Bromide) + aqueous KOH –> C2H5OH(Ethyl Alcohol) + KBr.

4) Rearrangement reactions An organic reactions in which the atoms or groups present in the organic molecules are rearranged by changing the position within in the molecule to from product. Cyclohexanone + NH2OH –> Cyclohexanoxime (undergoes rearrangement) –> Caprolactum.

5) Pericyclic reactions An organic reactions in which non-ionic, non-radical, groups undergo concerted, reversible mechanisms to form products. 1,3 butadiene (rearranges) —> cyclobutene.

6) Polymerization reactions An organic reactions in which the simpler units are combined to form complex molecules by addition, condensation etc. mechanisms. n C2H4 (Ethene) (polymerises) –> -(CH2-CH2)n- (polyethene)

Reaction type

Subtype

Comment

electrophilic addition Addition reactions

nucleophilic addition

include such reactions as halogenation, hydrohalogenation and hydration.

radical addition Elimination

include processes such as dehydration and are found to follow

reaction

an E1, E2 or E1cB reaction mechanism nucleophilic aliphatic

with SN1, SN2 and SNi reaction mechanisms

substitution nucleophilic aromatic substitution Substitution

nucleophilic acyl

reactions

substitution electrophilic substitution electrophilic aromatic substitution radical substitution

Organic redox

are redox reactions specific to organic compounds and are very

reactions

common. 1,2-rearrangements

Rearrangement reactions

pericyclic reactions metathesis

Alkanes are generally unreactive, but can participate in oxidation, halogenation, and cracking reactions.

1. Oxidation Reactions The most important reaction that alkanes undergo is combustion. Smaller, linear alkanes generally oxidize more readily than larger, more branched molecules. Alkanes can be burned in the presence of oxygen to produce carbon dioxide, water, and energy; in situations with limited oxygen, the products are carbon monoxide, water, and energy. For this reason, alkanes are frequently used as fuel sources. The combustion of methane is shown:

CH4+2O2→CO2+2H2O+ energy

2. Halogenation With the addition of a halogen gas and energy, alkanes can be halogenated with the reactivity of the halogens proceeding in the following order: Cl2>Br2>I2. In this reaction, UV light or heat initiates a chain reaction, cleaving the covalent bond between the two atoms of a diatomic halogen. The halogen radicals can then abstract protons from the alkanes, which can then combine or react to form more radicals. Alkanes can be halogenated at a number of sites, and this reaction typically yields a mixture of halogenated products.

3. Thermal Cracking The complex alkanes with high molecular weights that are found in crude oil are frequently broken into smaller, more useful alkanes by thermal cracking; alkenes and hydrogen

gas are also produced by using this method. Thermal cracking is typically performed at high temperatures, and often in the presence of a catalyst. A mixture of products results, and these alkanes and alkenes can be separated by fractional distillation.

Radical Halogenation of Alkanes

Reaction type: Radical Substitution

In the absence of a spark or a high-intensity light source, alkanes are generally inert to chemical reactions. However, anyone who has used a match to light a gas burner, or dropped a match onto charcoal coated with lighter fluid, should recognize that alkanes burst into flame in the presence of a spark. It doesn't matter whether the starting material is the methane found in natural gas, CH4(g) + 2 O2(g)

CO2(g) + 2 H2O(g)

the mixture of butane and isobutane used in disposable cigarette lighters, 2 C4H10(g) + 13 O2(g)

8 CO2(g) + 10 H2O(g)

the mixture of C5 to C6 hydrocarbons in charcoal lighter fluid, C5H12(g) + 8 O2(g)

5 CO2(g) + 6 H2O(g)

or the complex mixture of C6 to C8 hydrocarbons in gasoline. 2 C8H18(l) + 25 O2(g)

16 CO2(g) + 18 H2O(g)

Once the reaction is ignited by a spark, these hydrocarbons burn to form CO2 and H2O and give off between 45 and 50 kJ of energy per gram of fuel consumed. In the presence of light, or at high temperatures, alkanes react with halogens to form alkyl halides. Reaction with chlorine gives an alkyl chloride.

light CH4(g) + Cl2(g)

CH3Cl(g) + HCl(g)

Reaction with bromine gives an alkyl bromide. light CH4(g) + Br2(l)

CH3Br(g) + HBr(g)

Alkenes occur in similar mechanisms and has common reaction feature: The relatively loosely held π electrons of the carbon-carbon double bond are attracted to an electrophile. Thus, each reaction starts with the addition of an electrophile to one of the sp2 carbons of the alkene and concludes with the addition of a nucleophile to the other sp2 carbon. Alkene involves in three addition reactions: Hydrogenation, Halogenation, and Hydration.

1) Hydrogenation The double bond of an alkene consists of a sigma (σ) bond and a pi (π) bond. Because the carbon-carbon π bond is relatively weak, it is quite reactive and can be easily broken and reagents can be added to carbon. Reagents are added through the formation of single bonds to carbon in an addition reaction This is the reaction of the carbon-carbon double bond in alkenes with hydrogen in the presence of a metal catalyst. In a hydrogenation reaction, two hydrogen atoms are added across the double bond of an alkene, resulting in a saturated alkane. Hydrogenation of a double bond is a thermodynamically favorable reaction because it forms a more stable (lower energy) product. Example:

2) Halogenation The alkene halogenation reaction, specifically bromination or chlorination, is one in which a dihalide such as Cl2 or Br2 is added to a molecule after breaking the carbon to carbon double bond. The halides add to neighboring carbons from opposite faces of the molecule. The resulting product is a vicinal (neighboring) dihalide. Example:

3) Hydration

When water is added to an alkene, no reaction takes place, because there is no electrophile present to start a reaction by adding to the nucleophilic alkene. The O--H bonds of water are too strong – water is too weak acid – to allow the hydrogen to act as an electrophilic for this reaction. If, however, an acid such as HCL or H2SO4 is added to the solution, a reaction will occur because the acid provides an electrophile. The product of the reaction is an alcohol. The addition of water to a molecule is called hydration, so we can say that an alkene will be hydrated in the presence of water and acid.

The first two steps of the mechanism for the acid-catalyzed addition of water to an alkene are essentially the same as the two steps of the mechanism for the addition of a hydrogen halide to an alkene: The electrophile (H+) adds to the sp2 carbon that is bonded to the greater number of hydrogen, and the nucleophile (H2O) adds to the other sp2 carbon.

Alkenes and Alkynes have the same physical properties similar to those of alkanes. All are insoluble in water and all are soluble in nonpolar solvents such as hexane. They are less dense than water and, like any other series of compounds, have boiling points that increase with increasing molecular weight. Alkynes are more linear than alkanes, causing alkynes to have stronger van der Waals interactions. As a result, an alkyne has higher boiling point than an alkene containing the same number of carbon atoms. Like alkenes, alkynes involves in three addition reactions: Hydrogenation, Halogenation, and Hydration.

1) Hydrogenation Like alkenes, the main pathway found in the reactions of alkynes is “addition” – that is, breaking the C-C π bond and forming two new single bonds to carbon. The product of an addition reaction to an alkyne is an alkene Alkynes are converted into alkanes by reduction with 2 molar equivalents of 𝐻2 over a palladium catalyst. The reaction proceeds through an alkene intermediate, and the reaction can be stopped at the alkene stage if the right catalyst is used. The catalyst most often used for this purpose is the Lindlar catalyst, a specially prepared form of palladium metal. Hydrogenation occurs with syn stereochemistry, alkynes give cis alkenes when reduced. Example:

A. Complete reduction or hydrogenation On reacting with strong reducing agents like palladium, platinum, nickel or rhodium alkynes are reduced to alkanes. For example propyne is reduced to propane. CH3-C = CH + 2H2 $\to $ CH3-C The heats of hydrogenation is double that of corresponding alkenes. Like alkenes the heats of hydrogenation depends on nature of branching in alkynes. Due to +I effect the alkyl groups release electrons to carbon atom and hence the heats of hydrogenation is reduced. So the heats of hydrogenation of 1-pentyne will be more than that of 2-pentyne. CH3-CH2-CH2-C = CH > CH3-CH2-C = C-CH3 H2-CH3 B. Partial reduction or hydrogenation Alkynes on partial reduction with poor catalysts give alkenes. The partial reduction of alkynes can be done in two ways.By reacting with Palladium in Calcium carbonate / Palladium in barium sulphate. Alkynes on treating with palladium in barium sulphate give cis alkenes. For example 2-Butyne on reacting with palladium in barium sulphate give cis 2-Butene. CH3-C = C-CH3 + H2 → By reacting with alkali metal in liquid ammonia. Alkynes on treating with alkali metals in liquid ammonia give trans alkenes. For example 2-butyne on reacting with sodium in liquid ammonia give trans-2-butene.

CH3-C = C-CH3 + H2 →

2) Halogenation The reaction between a hydrogen halide (HX) and an alkyne yields a vinyl halide with Markovnikov orientation. A subsequent addition of HX to the product can occur because the vinyl halide still contains a double bond. This addition yields an alkyl dihalide and the formation cannot easily be prevented when HX is added to an alkyne, as the intermediate carbenium ion is stabilized by a +M effect of the halogen substituent. Markovnikov’s rule:

Hydrogen adds to the carbon with the greatest number of hydrogens, the halogen adds to the carbon with fewest hydrogens. Protination occurs on the more stable carbocation. With the addition of HX, haloalkenes form. With the addition of excess HX, you get anti addition forming a geminal dihaloalkane. Example:

3) Hydration As with alkenes, the addition of water to alkynes requires a strong acid, usually sulfuric acid, and is facilitated by mercuric sulfate. However, unlike the additions to double bonds which give alcohol products, addition of water to alkynes gives ketone products ( except for acetylene which yields acetaldehyde.

Benzene is a particularly stable compound because its resonance stabilization – the extra stability it gains from having delocalized electrons – is unusually large. Compounds with unusually large amount of resonance stabilization are called aromatic compounds. Aromatic heterocyclic compounds A compound does not have to be a hydrocarbon to be aromatic. Many heterocyclic compound are aromatic. Heterocyclic compound a cyclic compound in which one (or more) of the ring atoms is an atom other than carbon.

How benzene reacts? •

Aromatic compounds (such as benzene) undergo electrophilic aromatic substitution reactions – an electrophile substitutes for one of the hydrogens attached to the benzene ring.

•

Now let’s look at why this substitution reaction occurs. As a consequence of the π electrons above and below the plane of its ring, benzene is a nucleophile. It will, therefore, react with an electrophile (Y+). When an electrophile attaches itself to a benzene ring, a carbocation intermediate is formed.

•

This should remind you of the first step in an electrophilic addition reaction of an alkene. The alkene reacts with an electrophile and forms a carbocation intermediate. In the second step of an electrophile addition reaction, the carbocation reacts with a nucleophile (Z-) to form an addition product.

•

•

If the carbocation intermediate formed from the reaction of benzene with an electrophile were to react similarly with a nucleophile. The addition product would not be aromatic. If, however, the carbocation loses a proton from the site of electrophile attack, the aromaticity of the benzene ring is restored. Because the aromatic substitution product is much stable than the nonaromatic addition product, benzene undergoes electrophilic substitution reactions that preserve aromaticity rather than electrophilic addition reactions – the reactions characteristics of alkenes – that would destroy aromaticity. The substitution reaction is more precisely called a electrophilic aromatic substitution reaction since the electrophile substitutes for a hydrogen of an aromatic compound.

GENERAL MECHANISMS FOR ELECTROPHILIC AROMATIC SUBSTITUTION REACTIONS

•

The following are the five most common electrophilic aromatic substitution reactions: Halogenation: A bromine (Br) or a chlorine (Cl) substitutes for a hydrogen

HALOGENATION OF BENZENE The bromination or chlorination of benzene requires a Lewis acid catalyst such as ferric bromide or ferric chloride. Recall that a Lewis acid is a compound that accepts a share in an electron pair. •

•

Bromination

Chlorination

The reaction of benzene with Br2 or Cl2 requires a catalyst because of the stability of benzene is much less reactive than an alkene, therefore, it requires a better electrophile. Donating a lone pair to the Lewis acid weakens the Br – Br (or Cl – Cl) bond, which makes Br2 (or Cl2) a better electrophile.

Only one of the three resonance contributors of the carbocation intermediates is shown in this and subsequent mechanisms. Each carbocation intermediate actually has three resonance contributors. In the last step of the reaction, a base (:B) from the reaction mixture (e.g., FeBr4 , solvent) removes a proton from the carbocation intermediate.

NITRATION OF BENZENE Nitration of benzene with nitric acid requires sulfuric acid as a catalyst.

To generate the necessary electrophile, sulfuric acid protonates nitric acid. Loss of water from protonated nitric acid forms a nitronium ion, the electrophile required for nitration.

Remember that any base (:B) present in the reaction mixture () can remove the proton in the second step of the aromatic substitution reaction.

SULFONATION OF BENZENE Fuming sulfuric acid (a solution of SO3 in sulfuric acid) or concentrated sulfuric acid is used to sulfonate aromatic rings.

Take a minute to note the similarities in the mechanisms for forming the SO3H electrophile for sulfonation and the NO2 electrophile for nitration.

FRIEDEL – CRAFTS ACYLATION OF BENZENE Two electrophilic substitution reactions bear the names of chemists Charles Friedel and James Crafts. Friedel – Crafts acylation places an acyl group on a benzene ring.

The electrophile (an acylium ion) required for a Friedel-Crafts acylation is formed by the reaction of an acyl chloride with AlCl3 , a Lewis acid. An acyl chloride has a chlorine in place of the OH group of a carboxylic acid.

FRIEDEL – CRAFTS ALKYLATION OF BENZENE The Friedel-Crafts alkylation places an alkyl group on a benzene ring.

The electrophile in this reaction is a carbocation that is formed from the reaction of an alkyl halide with AlCl3. Alkyl fluorides, alkyl chlorides, alkyl bromides, and alkyl iodides can all be used.

Reaction type: Nucleophilic Substitution (SN1 or SN2)

alcohol below with H2SO4 leads to formation of a secondary carbocation, followed by a hydride shift to give a tertiary carbocation, followed by deprotonation at whichever β carbon leads to the most substituted alkene. SN1 MECHANISM FOR REACTION OF ALCOHOLS WITH HBr Step 1: An acid/base reaction. Protonation of the alcoholic oxygen to make a better leaving group. This step is very fast and reversible. The lone pairs on the oxygen make it a Lewis base.

Step 2: Cleavage of the C-O bond allows the loss of the good leaving group, a neutral water molecule, to give a carbocation intermediate. This is the rate determining step (bond breaking is endothermic)

Step 3: Attack of the nucleophilic bromide ion on the electrophilic carbocation creates the alkyl bromide.

Hydrolysis of Esters

Reaction type: Nucleophilic Acyl Substitution

MECHANISM OF THE BASE HYDROLYSIS OF ESTERS

Step 1: The hydroxide nucleophiles attacks at the electrophilic Cofthe ester C=O, breaking the π bond and creating thetetrahedral intermediate. Step 2: The intermediate collapses, reforming the C=O results in the loss of the leaving group the alkoxide, RO-, leading to the carboxylic acid.

Step 3: An acid / base reaction. A very rapid equilibrium where the alkoxide,RO- functions as a base deprotonating the carboxylic acid, RCO2H, (an acidic work up would allow the carboxylic acid to be obtained from the reaction).

General mechanism 1) Nucleophilic attack on the carbonyl

2) Leaving group is removed

Substitution of the Hydroxyl Hydrogen This reaction class could be termed electrophilic substitution at oxygen, and is defined as follows (E is an electrophile). RCO2–H + E(+)

RCO2–E + H(+)

Carboxylic Acid Synthesis By Oxidation

+ MnO2

Hydrolysis

+ HCl

Reactions of Aldehydes and Ketones The Carbonyl group of Aldehydes and Ketones reactions fall into three main groups: – Reactions with acids – Addition reactions – Oxidation

Aldehydes and Ketones. Nucleophilic Addition to C=O 

Strong nucleophiles (anionic) add directly to the C=O to form the intermediate alkoxide. The alkoxideis then protonated on work-up with dilute acid.



Weaker nucleophiles (neutral) require that the C=O be activated prior to attack of the Nu.

This can be done using a acid catalyst which protonates on the Lewis basic O and makes the system more electrophilic. Nucleophilic addition reactions are an important class of reactions that allow the interconversion of C=O into a range of important functional groups.

What does the term "nucleophilic addition" imply ? A nucleophile, Nu-, is an electron rich species that will react with an electron poor species (here the C=O) An addition implies that two systems combine to a single entity. There are three fundamental events in a nucleophilic addition reaction: 1. formation of the new s bond between the nucleophile, Nu, to the electrophilic C of the C=O group 2. breaking of the p bond to the O resulting in the formation of an intermediate alkoxide 3. protonation of the intermediate alkoxide to give an alcohol derivative Depending on the reactivity of the nucleophile, there are two possible general scenarios: 

Strong nucleophiles (anionic) add directly to the C=O to form the intermediate alkoxide. The alkoxides are then protonated on work-up with dilute acid.

Examples of such nucleophilic systems are : RMgX, RLi, RCºCM, LiAlH4, NaBH4 

Weaker nucleophiles (neutral) require that the C=O be activated prior to attack of the Nu.

This can be done using a acid catalyst which protonates on the Lewis basic O and makes the system more electrophilic.

Examples of such nucleophilic systems are : H2O, ROH, R-NH2 The protonation of a carbonyl gives a structure that can be redrawn in another resonance form that reveals the electrophilic character of the C since it is a carbocation.

Reversible Addition Reactions A. Hydration and Hemiacetal Formation It has been demonstrated (above) that water adds rapidly to the carbonyl function of aldehydes and ketones. In most cases the resulting hydrate (a geminal-diol) is unstable relative to the reactants and cannot be isolated. Exceptions to this rule exist, one being formaldehyde (a gas in its pure monomeric state). Here the weaker pi-component of the carbonyl double bond, relative to other aldehydes or ketones, and the small size of the hydrogen substituents favor addition. Thus, a solution of formaldehyde in water (formalin) is almost exclusively the hydrate, or polymers of the hydrate. Similar reversible additions of alcohols to aldehydes and ketones take place. The equally unstable addition products are called hemiacetals.

R2C=O + R'OH

R'O–(R2)C–O–H (a hemiacetal)