20.1Types of organic reactions HL only Syed Arshad Mushtaq Chemistry Teacher Australian School of Abu Dhabi

Nucleophilic substitution reactions

Learning outcomes Understand: Nucleophilic unimolecular substitution reactions are represented by SN1 and nucleophilic bimolecular substitution reactions are represented by SN2. Carbocation intermediates are formed in SN1 reactions whereas SN2 reactions involve a concerted reaction with a transition state. The predominant mechanism for tertiary halogenoalkanes is SN1 and for primary halogenoalkanes it is SN2. Secondary halogenoalkanes react by both mechanisms. The rate determining step (slow step) for SN1 reactions depends only on the concentration of the halogenoalkane, rate = k[R−X]. For SN2 reactions, rate = k[R−X][Nu]. SN2 is stereospecific and involves inversion of configuration at the carbon atom. SN2 reactions are favoured by aprotic, polar solvents and SN1 reactions are favoured by protic, polar solvents

Learning outcomes Apply knowledge to: Explain why a hydroxide ion is a better nucleophile than a water molecule. Deduce the mechanism of the nucleophilic substitution reactions of halogenoalkanes with aqueous sodium hydroxide in terms of SN1 and SN2 reaction mechanisms. Explain how the rate depends upon the identity of the leaving group (i.e. the halogen), whether the halogenoalkane is primary, secondary or tertiary and on the choice of solvent. Outline the difference between protic and aprotic solvents.

Substitution Reactions In a substitution reaction, one atom or group of atoms, takes the place of another in a molecule Examples CH3CH2Br + KCN  CH3CH2CN + KBr (CH3)3CCl + NaOH  (CH3)3 COH + NaCl 5

Nucleophilic Substitution A nucleophile is a molecule or ion that has a high electron density. It is attracted to atoms in molecules with a lower electron density. It may replace another group in an organic molecule. The molecule to which the nucleophile is attracted is called the substrate The group that the nucleophile replaces is called the leaving group These reactions are known as nucleophilic substitutions. 6

Nucleophilic Substitution One covalent bond is broken as a new covalent bond is formed The general form for the reaction is Nu:- + R-X  R-Nu + X: Nucleophile Substrate Product Leaving group 7

Nucleophilic Substitution Nu:- + R-X  R-Nu + X: The bond to the leaving group is broken The leaving group takes both electrons that formed the bond with it The nucleophile provides the electrons to form the new bond Nucleophile Substrate Product Leaving group 8

Nucleophilic Substitution halogenoalkanes commonly undergo nucleolophilic substitution reactions. The nucleophile displaces the halide leaving group from the halogenoalkane. There are two common ways for nucleophilic substitutions to occur. They are known as SN1 and SN2. Nucleophile Substrate Product Leaving group 9

Examples of Nucleophilic Substitutions Nucleophilic substitutions may be SN1 or SN2 10

Nucleophilic Substitution Bimolecular or SN2 A reaction is bimolecular when the rate depends on both the concentration of the substrate and the nucleophile. SN2 mechanisms occur most readily with methyl compounds and primary haloalkanes 11

SN2 Mechanism The general form for an SN2 mechanism is shown above. Nu:- = nucleophile 12

An Example of a SN2 Mechanism The nucleophilic substitution of ethyl bromide is shown above. This reaction occurs as a bimolecular reaction. The rate of the reaction depends on both the concentration of both the hydroxide ion and ethyl bromide This is a one step process since both the nucleophile and the substrate must be in a rate determining step. 13

Nucleophilic Substitution Unimolecular or SN1 A unimolecular reaction occurs when the rate of reaction depends on the concentration of the substrate but not the nucleophile. A unimolecular reaction is a two step process since the subtrate and the nucleophile cannot both appear in the rate determining step SN1 mechanisms occur most readily with tertiary haloalkanes and some secondary haloalkanes. 14

SN1 Mechanism The general form for an SN1 mechanism is shown above. Nu:- = nucleophile 15

SN1 Mechanism The first step is the formation of the carbocation. It is the slow step. The rate of the reaction depends only on the concentration of the substrate. 16

Inversion of configuration SN1 and SN2 Reactions SN1 SN2 Rate =k[RX] =k[RX][Nuc:-] Carbocation intermediate? Yes No Stereochemistry mix Inversion of configuration Rearrangement ~H, ~ CH3 possible No rearrangements 17

Aprotic polar solvent and protic solvent POLAR PROTIC SOLVENTS (polar and ability to be H-bond donor) have dipoles due to polar bonds can H atoms that can be donated into a H-bond examples are the more common solvents like H2O and ROH remember basicity is also usually measured in water anions will be solvated due to H-bonding, inhibiting their ability to function as Nu POLAR APROTIC SOLVENTS (polar but no ability to be H-bond donor)have dipoles due to polar bonds don't  have H atoms that can be donated into a H-bond examples are acetone, acetonitrile anions are not solvated and are "naked" and reaction is not inhibited https://www.youtube.com/watch?v=FSxaoxPu124

Overall All nucleophiles will be more reactive in aprotic than protic solvents Those species that were most strongly solvated in polar protic solvents will "gain" the most reactivity in  polar aprotic (e.g. F-). Polar aprotic solvents are typically only used when a polar protic solvent  gives poor results due to having a weak Nu, (esp. F-, -CN, RCO2-)

HYDROXIDE – A BETTER NUCLEOPHILE Nucleophiles are reactants that are electron rich so they are very attracted to electron deficient atoms. Nucleophiles have a lone pair of electrons and may also carry a negative charge: H2O, OH-, NH3, CN- The hydroxide ion is a stronger nucleophile than water because it carries a negative charge.

Electrophilic addition reactions

Learning outcomes Understand: Electrophiles are electron-deficient species that can accept a pair of electrons from a nucleophile. All electrophiles are Lewis acids. The major product in electrophilic addition reactions involving asymmetrical alkenes with hydrogen halides and interhalogens can be predicted using Markovnikov’s rule. The formation of the major product can be explained by the relative stability of the possible intermediate carbocations in the reaction mechanism.

Learning outcomes Apply their knowledge to: Deduce the mechanism of the electrophilic addition reactions of alkenes with hydrogen halides and with halogens and or interhalogens.

Addition Mechanisms Electrophilic addition occurs in reactions involving containing carbon-carbon double bonds - the alkenes. An electrophile is a molecule or ion that is attracted to electron-rich regions in other molecules or ions. Because it is attracted to a negative region, an electrophile carries either a positive charge of a partial positive charge 25

Electrophilic Addition Electrophilic addition occur in molecules where there are delocalized electrons. The electrophilic addition to alkenes takes the following general form: 26

ALKENES + HALOGENS (Ethene + bromine) When ethene gas is bubbled through bromine, the brown color disappears as it forms 1,2-dibromoethane. Remember that the color change shows presence of unsaturation. http://www.bbc.co.uk/staticarchive

The mechanism is as follows: Bromine, a non-polar molecule, becomes polarized as it approaches the electron rich area of the alkene. The electron rich area repels the electrons on the bromine molecule causing an area of positive charge and an area of negative charge.

The bromine atom nearest the alkene’s double bond gains a partial positive charge and acts as the electrophile. The bromine molecule splits heterolytically forming Br+ and Br- and the initial attack on the ethene in which the pi bond breaks is carried out by Br+. This first step is slow forming an unstable positive carbocation intermediate.

This carbocation then reacts rapidly with the negative bromide ion forming the product.

If you mix this reaction with the presence of chlorine ions, the carbocation readily reacts with either the Cl- or Br- ions. However, no dichloro compound is ever formed confirming that the initial attack is from the Br+ ion.

ALKENES + HYDROGEN HALIDES (Ethene + hydrogen bromide) The reaction occurs by a similar reaction as alkenes + halogens. HBr is a polar molecule that undergoes heterolytic fission to form H+ and Br-. The electrophile, H+, attacks the alkene’s double bond. The unstable positive carbocation intermediate then reacts readily with the Br- to form the addition product.

A piece of evidence that supports this mechanism is that the reaction if favored by a polar solvent that facilitates the production of ions from heterolytic fission. HI > HBr > HCl

Markovnikoff’s Rule Actually there are two possible carbocations that could be formed. In may cases this would result in two possible products. However only one form is preferred “Birds of a feather flock together!” The hydrogen ion will tend to migrate to the side with the greater number of hydrogen atoms. This preference is known as Markovnikoffs Rule. 34

Example The electrophilic addition of alkenes occurs in two stages First there is the formation of a carbocation Followed by the attack the chloride ion to form the addition product 35

Sample Problem Write a mechanism for the electrophilic addition of HBr to 1-butene. 36

Please note in picture partial charges on H-Br are not correct Solution Write a mechanism for the electrophilic addition of HBr to 1-butene. Solution Please note in picture partial charges on H-Br are not correct 37

ALKENES + INTERHALOGENS (Ethene + BrCl) An interhalogen is a compound made up of two halogens. Chlorine is more electronegative than bromine so BrCl is polarized so that Br has a partial positive charge and is the electrophile and Cl has the partial negative charge and will react with the carbocation. Draw the reaction mechanism.

SAMPLE PROBLEM Write the names and structures for the two possible products of the addition of the interhalogen BrCl to propene. Which is likely to be the major product? Explain.

Solution

Electrophilic substitution reactions

Learning outcomes Understand: The simplest arene (aromatic hydrocarbon compound) is benzene. Benzene has a delocalized structure of π bonds around its six-membered ring. Each carbon to carbon bond has a bond order of 1.5. Benzene undergoes electrophilic substitution reactions.

Learning outcomes Apply knowledge to: Deduce the mechanism for the nitration of benzene using concentrated nitric acid and a catalyst of concentrated sulfuric acid.

Orbital model of Benzene Structure Benzene is built from hydrogen atoms (1s1) and carbon atoms (1s22s22px12py1). Promotion of electron Hybridization

sp2 hybrid orbital

sp2 hybrid orbital

Benzene undergoes electrophilic substitution reactions Electrophilic substitution reactions involving positive ions Benzene and electrophiles Because of the delocalised electrons exposed above and below the plane of the rest of the molecule, benzene is obviously going to be highly attractive to electrophiles - species which seek after electron rich areas in other molecules. The electrophile will either be a positive ion, or the slightly positive end of a polar molecule

The general mechanism The first stage The second stage

The electrophilic substitution reaction between benzene and nitric acid The facts Benzene is treated with a mixture of concentrated nitric acid and concentrated sulphuric acid at a temperature not exceeding 50°C. As temperature increases there is a greater chance of getting more than one nitro group, -NO2, substituted onto the ring. Nitrobenzene is formed.

The electrophilic substitution reaction between benzene and nitric acid The formation of the electrophile The electrophile is the "nitronium ion" or the "nitryl cation", NO2+. This is formed by reaction between the nitric acid and the sulphuric acid

The electrophilic substitution reaction between benzene and nitric acid The electrophilic substitution mechanism Stage one Stage two

Reduction Reactions

Learning outcomes Understand: Aldehydes can be reduced to primary alcohols. Carboxylic acids can be reduced first to aldehydes then to primary alcohols. Ketones can be reduced to secondary alcohols. Typical reducing agents are sodium borohydride, NaBH4, and lithium aluminium hydride, LiAlH4, (used to reduce carboxylic acids

Learning outcomes Apply knowledge to: Write equations for the reduction reactions of aldehydes to primary alcohols, ketones to secondary alcohols and carboxylic acids to aldehydes, using suitable reducing agents.

REDUCTION OF ALDEHYDES AND KETONES Reducing agents lithium tetrahydridoaluminate(III) (also known as lithium aluminium hydride)  LiAlH4 Sodium tetrahydridoborate(III) (sodium borohydride). NaBH4

Reducing agents LiAlH4 NaBH4 Both reducing agents produce the hydride ion, H-, which acts as a nucleophile on the electron deficient carbonyl carbon. LiAlH4 NaBH4 Lithium aluminum hydride, LiAlH4, in anhydrous conditions, such as dry ether followed by aqueous acid. LiAlH4 have violent reaction and only used for reduction of carboxylic acid Sodium borohydride, NaBH4 in aqueous or alcoholic solution NaBH4 is the safer reagent but is not reactive enough to reduce carboxylic acids

REDUCTION OF ALDEHYDES AND KETONES The overall reactions The reduction of an aldehyde Reduction of an aldehyde leads to a primary alcohol. The reduction of a ketone Reduction of a ketone leads to a secondary alcohol

Reduction of carboxylic acid Carboxylic acids are first reduced to aldehydes and than to primary alcohols

Nitrobenzene to Penylamine Reduction Reaction

Learning out comes Application and skills Describe the two-stage conversion of nitrobenzene to phenylamine

Nitrobenzene to phenylamine The conversion is done in two main stages: Stage 1: conversion of nitrobenzene into phenylammonium ions Nitrobenzene is reduced to phenylammonium ions using a mixture of tin and concentrated hydrochloric acid.

Nitrobenzene to phenylamine Stage 2: conversion of the phenylammonium ions into phenylamine Sodium hydroxide solution is added to the product of the first stage of the reaction.

Summary Benzene to Phenylamine

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