Synthesis of Organic Compounds

Homolytic fission

• results in the formation of two neutral radicals

• occurs when each atom retains one electron from the σ covalent bond and the bond breaks evenly

• normally occurs when non-polar covalent bonds are broken

Explain why heterolytic fission rather than homolytic fission is used for organic synthesis

• Reactions involving homolytic fission tend to result in the formation of very complex mixtures of products, making them unsuitable for organic synthesis.

• Reactions involving heterolytic fission tend to result in far fewer products than reactions nvolving homolytic fission, and so are better suited for organic synthesis.

Heterolytic fission

• results in the formation of two oppositely charged ions

• occurs when one atom retains both electrons from the σ covalent bond and the bond breaks unevenly

• normally occurs when polar covalent bonds are broken

Heterolytic fission of CH₃I

Carbocation

An ion with a positively charged carbon atom

Carbonion

An ion with a negatively charged carbon atom

Nucleophiles

negatively charged ions or neutral molecules that are electron rich

Examples of nucleophiles

Cl^- , Br^- , OH^- , CN^- , NH₃ and H₂O

Properties of Nucleophiles

• attracted towards atoms bearing a partial ( ) δ+ or full positive charge

• capable of donating an electron pair to form a new covalent bond

Electrophiles

Positively charged ions or neutral molecules that are electron deficient

Examples of electrophiles

H⁺, NO₂^-, SO₃

Properties of Electrophiles

• attracted towards atoms bearing a partial (δ^-) or full negative charge

• capable of accepting an electron pair to form a new covalent bond

Explain why the ammonia molecule is a nucleophile

The presence of lone pair on the N atom

Haloalkanes (alkyl halides)

Substituted alkanes in which one or more of the hydrogen atoms is replaced with a halogen atom

Monohaloalkanes

Haloalkane containing only one halogen atom

Monohaloalkanes can be classified as:

primary, secondary or tertiary according to the number of alkyl

groups attached to the carbon atom containing the halogen atom

Monohaloalkane —?—> Alkene

• ELIMINATION REACTION

• using a strong base, such as potassium or sodium hydroxide in ethanol

Monohaloalkane + ? ——> Alcohol

• NUCLEOPHILIC SUBSTITUTION REACTION

• Monohaloalkane + aqueous alkali —> alcohol

Monohaloalkane + ? ——> Ether

• NUCLEOPHILIC SUBSTITUTION REACTION

• Monohaloalkane + alcoholic alkoxide —> ether

Monohaloalkane + ? ——> nitrile

• NUCLEOPHILIC SUBSTITUTION REACTION

• Monohaloalkane + ethanolic cyanide —> nitriles

• Chain length increased by one carbon atom

S_N1 Reaction

Nucleophilic substitution reaction with one species in the rate determining step and occurs in a minimum of two steps via a trigonal planar carbocation intermediate

State the substitution reaction mechanisms for primary, secondary and tertiary haloalkanes and explain why they react by that reaction mechanism

• Primary and secondary haloalkanes tend to react via S_N2 mechanism

• Tertiary haloalkanes tend to react via S_N1 reactions due to steric hindrance of the side groups in the tertiary haloalkane blocking the attack of the nucleophile for the δ⁺on the carbon atom in the carbon to halogen bond. Alkyl groups off this carbon provide inductive stabilisation of the carbocation intermediate due to the repelling ability of the alkyl groups.

S_N2 Reaction Mechanism

nucleophilic substitution reaction with two species in the rate determining step and occurs in a single step via a single five-centred, trigonal bipyramidal transition state

Nucleophilic substitution mechanism

Alcohols

substituted alkanes in which one or more of the hydrogen atoms is replaced with a hydroxyl functional group, –OH group

Alcohols can be prepared from:

• haloalkanes by nucleophilic substitution with aqueous alkali

• alkenes by acid-catalysed hydration (addition)

• aldehydes and ketones by reduction using a reducing agent such as lithium aluminium hydride

Alcohol —?—> alkene

• DEHYDRATION

• Uses aluminium oxide, concentrated sulfuric acid or

  concentrated phosphoric acid

Oxidation of primary alcohols

Primary alcohols can be oxidised to form aldehydes and then carboxylic acids

Oxidation of secondary alcohols

Secondary alcohols can be oxidised to form ketones. Ketones cannot be oxidised

Oxidising agents used to oxidise alcohols

• Acidified dichromate

• Acidified permanganate

• Hot copper (II) oxide (used in synthesis reactions)

Formation of alcoholic hydroxides

Alcohols can react with some reactive metals such as potassium or sodium to form alcoholic hydroxides, which can then be reacted with monohaloalkanes to form ethers

Formation of esters

• Esters can be formed by the reaction of alcohols with carboxylic acids using concentrated sulfurique acids or concentrated phosphoric acid as a catalyst

• Esters can also be formed by reaction of alcohols with acid chlorides. Carboxylic acids can be converted to acid chlorides by reaction with SOCl₃, PCl₃ or PCl_5. Although this is a two-step preparation, this gives a faster reaction than carboxylic acids and no catalyst is needed.

Hydroxyl groups in alcohols this gives a faster reaction than carboxylic acids and no catalyst is needed.

• Hydroxyl groups make alcohols polar, which gives rise to hydrogen bonding

• Hydrogen bonding can be used to explain the properties of alcohols including boiling points, melting points, viscosity and solubility or miscibility in water

Ethers

• Ethers can be regarded as substituted alkanes in which a hydrogen atom is replaced with an alkoxy functional group, - -OR

• They have the general general structure R' – O – R'', where R' and R'' are alkyl groups (oxygen bridging two alkyl groups together)

Naming ethers

Ethers are named as substituted alkanes. The alkoxy group is named by adding the ending ‘oxy’ to the alkyl substituent, and this prefixes the name of the longest carbon chain.

Name the ether

methoxypropane

Name the ether

2-methoxy-2-methylpropane

Hydrogen bonding in ethers

The lack of H bonding between ether molecules explains the relatively lower boiling points of ethers as compared with alcohols. However, when mixed with water, the polarity of ethers gives rise to some H bonding. Ethers with short alkyl groups do show some water solubility, however those with longer alkyl groups do not due to the hydrophobic nature of the longer non-polar hydrocarbon chain. ie. methoxymethane and methoxyethane are soluble in water; larger ethers are insoluble in water due to their increased molecular size.

Uses of ethers as solvents

Ethers are commonly used as solvents since they are relatively inert chemically and will dissolve many organic compounds, however, great care bust be exercised in their use due to their:

• Extreme volatility

• Flammability

• Potential for exposure to sunlight in resulting in their oxidation to peroxides, R-O-O-R, which are highly explosive. This is despite the tendency of ethers to be quite unreactive.

Halogenation of alkanes

• Is a slow reaction

• Requires the presence of UV light, usually from sunlight

• Can be described as a substitution reaction

• Is a chain reaction involving the formation of highly reactive atoms and free radicals, and consists of the steps initiation, propagation and termination (see reaction mechanism)

Explain how the type of halogen in a haloalkanes affects the reactivity of a haloalkane

The type of halogen bonded to the carbon affected the reactivity as for instance R-F bonds are very strong so very unreactive, whereas going down the halogen group, the R-X bond becomes weaker and so the alkyl halide becomes more reactive.

Alkyl halides are {nucleophiles/electrophiles}

Electrophiles

Monohaloalkane + ? ——> amine

• NUCLEOPHILIC SUBSTITUTION

• Monohaloalkane can react with ammonia to form an amine

Alkenes can be prepared by:

• dehydration of alcohols using aluminium oxide, concentrated sulfuric acid (H₂SO₄) or concentrated phosphoric acid (H₃PO4) (ELIMINATION)

• base-induced elimination of hydrogen halides from monohaloalkanes

Alkenes take part in electrophilic addition reactions with:

• hydrogen to form alkanes in the presence of a catalyst (hydrogenation)

• halogens to form dihaloalkanes (halogenation)

• hydrogen halides to form monohaloalkanes

• water using an acid catalyst to form alcohols (hydration)

Markovnikov’s Rule

Markovnikov’s rule states that when a hydrogen halide or water is added to an unsymmetrical alkene, the hydrogen atom becomes attached to the carbon with the most hydrogen atoms attached to it already. Markovnikov’s rule can be used to predict major and minor products formed during the reaction of a hydrogen halide or water with alkenes.

Using curly arrow notation, show the reaction mechanism for the addition of a hydrogen halide to ethene

Using curly arrow notation, show the reaction mechanism for the acid catalysed addition of water to ethene

The inductive stabilisation of intermediate carbocations formed during these reactions can be used to explain the products formed

The reaction mechanism for the addition of a halogen can be represented using curly arrows and showing the cyclic ion intermediate

Carboxylic acids can be prepared by:

• oxidising primary alcohols using acidified permanganate, acidified dichromate and hot copper(II) oxide

• oxidising aldehydes using acidified permanganate, acidified dichromate, Fehling’s solution and Tollens’ reagent

• hydrolysing nitriles, esters or amides

Reactions of carboxylic acids include:

• formation of salts by reactions with metals or bases

• condensation reactions with alcohols to form esters in the presence of concentrated sulfuric or concentrated phosphoric acid

• reaction with amines to form alkylammonium salts that form amides when heated

• reduction with lithium aluminium hydride to form primary alcohols

Amines

Organic derivatives of ammonia in which one or more hydrogen atoms of ammonia has been replaced by an alkyl group

Classification of amines

Amines can be classified as primary, secondary or tertiary according to the number of alkyl groups attached to the nitrogen atom.

Amine + acid —>

Salt

Hydrogen bonding in amine

Primary and secondary amines, but not tertiary amines, display hydrogen bonding. As a result, primary and secondary amines have higher boiling points than isomeric tertiary amines.

Solubility of amines

Primary, secondary and tertiary amine molecules can hydrogen-bond with water molecules, thus explaining the appreciable solubility of the shorter chain length amines in water

Explain how amine acts like a weak base in solution

Amines like ammonia are weak bases and dissociate to a slight extent in aqueous solution. The nitrogen atom has a lone pair of electrons which can accept a proton from water, producing hydroxide ions.

Benzene (C₆H₆)

Simplest member of the class of aromatic hydrocarbons

By referring to the structure of the benzene ring, explain why the benzene ring does not take part in addition reactions

• The benzene ring has a distinctive structural formula

• The stability of the benzene ring is due to the delocalisation of electrons in the conjugated system

• The presence of delocalised electrons explains why the benzene ring does not take part in addition reactions

Bonding in benzene

Each carbon atom can be regarded as going under a sp² hybridisation. The overlap of the sp² orbitals give rise to sigma bonds and the overlap of the unhybridised p orbitals give rise to pi bonds, in the case of benzene, the delocalised ring of six electrons.

Phenyl group

A benzene ring in which one hydrogen atom has been substituted by another group, –C₆H₅

Benzene rings can take part in electrophilic substitution reactions. Reactions at benzene rings include:

• halogenation by reaction of a halogen using aluminium chloride or iron(III) chloride for chlorination and aluminium bromide or iron(III) bromide for bromination

• alkylation by reaction of a haloalkane using aluminium chloride

• nitration using concentrated sulfuric acid and concentrated nitric acid

• sulfonation using concentrated sulfuric acid