Bayer Test, Dan Bromine Test

8/13/2019 Bayer Test, Dan Bromine Test

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Organic Reactions

Alkanes with chlorine and bromine

Homolytic fission takes placethe attacking species is a free radical.

In this reaction, all

curly arrows have half-heads. This denotes the transfer of a single electron. The mechanism is as

follows:

The initiating step is the breaking of the H-X bond by a photon of light as this bond is weaker

than the C-H or C-C bonds and therefore can be broken in this way.

Alkenes

Alkenes undergo electrophillic addition across the double bond.

Halogens

Halogens are symmetrical and add via the following mechanism:

Hydrogen Halides with unsymmetrical alkenes.


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An unsymmetrical alkene is e.g. propene, CH3CH=CH2. It is possible for the hydrogen to add to

either the number 1 or number 2 carbon atom in the molecule. Markownikoff s Rule states that

when a substance of the type HX undergoes an addition reaction with an unsymmetrical C=Cdouble bond, the main product is the one in which the hydrogen adds on to the carbon atom

which already has the most hydrogen atoms. Thus the major product (about 90%) will be 2-

chloropropane.

The reason for this can be seen by considering the mechanism for the reaction:

The secondary carbocation is more stable, as the surrounding alkyl groups can release electrons

to stabilise it. Since this carbocation is of lower energy (more stable), the activation energy toform it will be lower and it will be formed more quickly. Thus there will be more of these

carbocations available to react with the anion. This reaction is said to be thermodynamically

controlled.

Concentrated sulphuric acid

Alkenes react with concentrated sulphuric acid at room temperature to produce

alkylhydrogensulphates.

RCH=CHR+ H2SO4RCH(OSO2OH)CH2R

Note that if one of the carbon atoms across the double bond is at the end of the chain (i.e. a =CH2

group) the H will add on to this group.

Mechanism:


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Alkylhydrogensulphates are easily hydrolysed by water to form alcohols, reforming the acid.

R(OSO2OH) + H2O ROH + H2SO4

Since alkenes are formed by the cracking of oil, this is a method for manufacturing alcoholsindustrially. However, ethanol is made by the direct hydration of ethene using steam and

phosphoric acid as a catalyst, at 300C and 60atm.

Oxidation of alkenes with alkaline manganate (VII)

Ethene is oxidised to ethane-1,2-diol by alkaline manganate (VII), the manganate being reducedto green manganate (VI), MnO4

2-.

Overall equation:

This is Baeyers test for double bonds. Ethane-1,2-diol is used in car antifreeze and themanufacture of terylene.

Primary, secondary and tertiary alcohols

With acidified dichromate (VI)

Acidified dichromate is an orange solution, and acts as an oxidising agent.

Primary alcohol aldehyde carboxylic acid

Secondary alcohol ketone

Tertiary alcoholno reaction (oxidation involves breaking a C-C or C-H bond).


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Achieving oxidation to the carboxylic acid requires a concentrated solution of dichromate and

reflux.

Dehydrating agents

In the vapour phase, alcohol vapour can be passed over ho aluminium oxide (acts as a catalyst).In the case of ethanol, ethene is formed.

In the liquid state, concentrated sulphuric acid is used. This can produce an ether or an alkene,depending on the conditions used:

Concentrated H2SO4and ethanol at 170C gives ethene. The mechanism is as follows:

With ethanol in excess and at 140C the ethanol molecules can act as nucleophiles and canattack the intermediate. An ether is produced (in this case, ethoxyethane).

Excesssulphuric acid protonates the ethanol molecules, preventing them acting as nucleophiles.

Halogenation

Addition of solid PCl5to an alcohol produces copious steamy fumes of HCl and substitutes a

chloro group for theOH group.

Chlorination

The alcohol is heated with concentrated HCl in the presence of anhydrous ZnCl2catalyst.

Bromination


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The HBr required is produced in situ by the reaction of concentrated sulphuric acid with KBr.

This mixture is then heated with the alcohol. This is a messy reaction as Br2is also produced.

The substitution proceeds as above.

Iodination

A mixture of red phosphorus and iodine acts like phosphorus (III) iodide. This then carries out

the iodination. One other product is phosphonic acid.

3ROH + PI33RI + H3PO3

Primary amines with hydrogen ions

An amine can be viewed as an ammonia molecule in which an alkyl or aryl group has been

substituted for a hydrogen atom. Where just one hydrogen is replaced, the amine is a "primary"

amine with the functional group -NH2.

Some examples of aliphatic amines:-

CH3NH2methylamine

C2H5NH2ethylamine

C4H9NH2butylamine etc

An aromatic amine

C6H5NH2phenylamine

The amines, like ammonia, act as bases and accept H+ions. They are actually slightly stronger

bases than ammonia because the alkyl groups release electrons, which allow the nitrogen to

accept a proton more easily.

Carboxylic acids

Esterification

Acids react with alcohols to give esters and water. This reaction is catalysed by H+

ions, usuallyin the form of concentrated sulphuric acid as this removes water, pushing the equilibrium to the

right. As esters have no hydrogen bonds, they are more volatile than the other reagents and thuscan be removed by distillation during the process.

Esters are hydrolysed using either acid as a catalyst, in which case an equilibrium is set up, oralkali, in which case the salt of the acid is produced. This can then by converted back to the acid

using a mineral acid (e.g. H2SO4).


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Reduction

A powerful reducing agent is needed to reduce an acid. The once commonly used is lithium

tetrahydridoaluminate(III), or litium aluminium hydride. It needs to be used in completelyanhydrous conditions or hydrolysis of the agent takes place. The solvent usually used is dry

ethoxyethane, or ether. The first step of the mechanism is shown below.

Phosphorus pentachloride

When solid PCl5is added to a carboxylic acid at room temperature a vigorous reaction occurs,and HCl and an acyl chloride is produced.

Arenes

Arenes with nitrating mixture

The term "arene" is equivalent to the term "aromatic", referring to an (organic) compound

containing a benzene ring.

To nitrate benzene a mixture of concentrated nitric and sulphuric acids is needed. This mixture isrefluxed with the benzene at 60C. The reaction between the two produces the NO2+ion, which

attacks the electrons on the benzene ring, giving an electrophillic substitution.

HNO3+ 2H2SO4NO2++ H3O

++ 2HSO4

-

For activated arenes (e.g. phenol, toluene), dilute nitric acid and sodium nitrate is used.

Mechanism:

Oxidation of side chains with manganate (VII)


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Hot concentrated manganate (VII), alkaline, acidic or neutral, will oxidise all side chains on a

benzene ring to carboxylic acid groups. This is very useful in diagnosis, although not so in

synthesis.

Friedel-Crafts

The Friedel-Crafts reaction is a method of introducing a side chain onto a benzene ring. This is

useful because it allows compounds to be synthesised from the benzene. It is carried out using a

chloroalkane in the presence of anhydrous aluminium chloride as a catalyst. The mechanism is as

follows:

The chloroalkane reacts with the AlCl3to form an electrophile:

This then

substitutes into the benzene ring, reforming the catalyst.

If an acid chloride is used in the place of the chloroalkane, the same reaction takes place, but

leading to the first group on the chain being a carbonyl group, which may be useful for reactions.

Halogenoalkanes

Hydroxide ions

With a cold, dilute, aqueous solution of hydroxide ions nucleophillic substitution takes place by

the SN1 or SN2 mechanism. SN1 takes place mainly with tertiary halogenoalkanes (see module 2notes).

RX + OH-ROH + X

-

With a hot concentrated ethanolic solution of hydroxide ions elimination of HX takes place to

give an alkene.

RCH2CHXR+ OH-RCH=CHR+ H2O +X

-


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Obviously, the reaction is not as clear-cut as this. Some substitution takes place in the ethanolic

solution and some elimination in the aqueous case. The more extreme the conditions the greater

the yield of the required product will be.

Cyanide ions

With cyanide ions in ethanolic solution, nucleoplillic substitution takes place. It is necessary to

use the organic solvent as water reacts with the cyanide ions to form HCN and OH

ions, whichthen substitute instead. The mechanism is as follows:

If the halogenoalkane was optically active then the resulting compound will also be opticallyactive. If the CN increases the chain length then the compound is named as a nitrile. If not it is

named as a compound with a cyano group substituted.

With ammonia

With ammonia nucleophillic substitution takes place. Ammonia gas must be used under pressure

and heated in a sealed container. The equation is RX + NH3RNH2+ HX

This process has many problems, not least that the primary amine produced is a stronger base

than the ammonia itself, and therefore will react with the halogenoalkane itself. This is avoidedby using a great excess of ammonia. This is necessary also because the HX produced will react

with ammonia, but causes problems with the removal of the excess ammonia afterwards.

Grignard reagents

If a halogenoalkane is dissolved in dry ethoxyethane, it can be reacted with magnesium toproduce a Grignard reagent. It is essential for the conditions to be anhydrous, otherwise the

Grignard reagents will react with the water.

RX + Mg R Mg X

The distribution of the charge on the atoms should be noted:


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This is a carboanion, a very unusual species in organic chemistry, which can act as an

electrophile.

The reaction with water is:

R-Mg-X + H2O RH + Mg(OH)X

As can be seen, this uses up the reagent to form an alkane, which is virtually useless, and a

magnesium salt.

Reacting this complex with an aldehyde or a ketone gives a secondary or tertiary alcohol

respectively. The reaction mechanism for a general carbonyl compound is shown:

Thereaction is also possible with carbon dioxide, in which case a carboxylic acid is formed. This

produces a carboxylic acid with an extra carbon atom, which could be useful to produce

carboxylic acids that are not found in nature. The mechanism is basically the same:

In both cases, MgXCl is also produced. The hydrolysis could be carried out by water alone, butthe suspension produced is difficult to handle.

Reduction of nitrobenzene

Nitrobenzene is easily produced by the nitration of benzene. It can then be converted to

phenylamine by reduction. This is easier than trying to substitute ammonia into the benzene ring.

In the lab, the reaction is accomplished using tin metal and concentrated hydrochloric acid. Inindustry, this route is too expensive, and iron is used with the most dilute hydrochloric acid that

will carry out the reduction. The reaction with tin is:


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The reaction with iron is very similar, except that iron(III) oxide is formed instead of tin(IV)

chloride.

The production of azo dyes

Diazonium compounds are produced by reacting aromatic amines, particularly phenylamine,with nitrous acid, also known as nitric(III) acid. This is produced by dissolving sodium nitrate

(III) (sodium nitrite) in dilute hydrochloric acid. This gives the reaction NaNO2+ HCl NaCl +HNO2, where HNO2is nitrous acid. This is pale blue in colour and not very stable. It reacts with

phenylamine in the presence of excess acid to produce benzene diazonium chloride:

It is necessary to keep this reaction cold below 5Cotherwise the diazonium saltdecomposes to give nitrogen gas and a poor yield of phenol. This is achieved by adding ice to thereaction mixture. This reaction, as it produces diazonium salts, is called diazotisation.

Coupling

Couplingis the reaction of a diazonium salt with an activated aromatic compound. Possibilities are

aromatic amines and alcohols. This links the two aromatic groups with an N=N group, resulting

in highly coloured compounds used as dyes and acid base indicators. For example, benzenediazonium chloride with phenol and 2-napthol:

The reaction with 2-napthol can be used to distinguish between aliphatic and aromatic amines.

With aliphatic amines, stable diazonium ions do not form, and therefore no coloured precipitateis formed.

Carbonyl compounds


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Hydrogen cyanide

Toprovide this addition, an aqueous solution of potassium or sodium cyanide is used, but the

overall reaction is the addition of HCN. The reaction is inhibited by acids. This is a nucleophillic

addition reaction; the mechanism is as follows:

The compound produced is usually referred to as the cyanohydrin of the carbonyl compoundit can also be named systematically. The reaction adds a carbon atom to the chain, and also

allows acid hydrolysis to -hydroxycarboxylic acids.

2,4-dinitrophenylhydrazine (Bradys reagent)

This is

addition followed by elimination, also called a condensation reaction. The product formed is ayellow precipitate, giving a qualitative diagnosis of a carbonyl compound, which can be

recrystalised and the melting point determined to give a precise diagnosis of which carbonyl was

present. The mechanism for the reaction is:

As shown, the initial product rapidly looses water to form a hydrazone. This is the substance that

is analysed.

TollensReagent (ammonacial silver nitrate solution)

Tollensreagent contains Ag+ions, which can be reduced to silver metal. This reaction is

possible with an alcohol or an aldehyde, but not with a ketone, as a ketone cannot be oxidised. Itcan thus be used to distinguish between an aldehyde and a ketone. With a positive test (aldehyde)

a silver mirror forms on the inside of the test tube used.


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The iodoform test

The iodoform test is a test for compounds that contain either of the following groups:

This includes ethanal and ethanol. If a methyl secondary alcohol is used it will be oxidised to the

methyl ketone before the main part of the process takes place. The compound being tested is

reacted with iodine in sodium hydroxide solution or sodium chlorate (I) and potassium iodate

solution. A bright yellow precipitate of iodoform indicates a positive test. The reaction startswith the substitution of the hydrogens in the methyl group for iodine atoms. This causes a great

withdrawing of electrons from the C-C bond joining the methyl group to the ketone group,

allowing nucleophillic attack and fission of the bond:

The products are iodoform and a degraded carboxylic acid. This reaction is of more value fordiagnostic purposes than for synthesis.

Sodium tetrahydridoborate (III)sodium borohydrideNaBH4

This is a milder reducing agent than LiAlH4, and will not reduce carboxylic acids and their

derivatives. However, it is easier to use because it can be used in aqueous solution, and ischeaper. It reduces aldehydes to primary alcohols and ketones to secondary alcohols.

Ethanoyl chlorideCH3COCl

Acid chlorides, or acyl chlorides, fume in air (HCl). The presence of theCl group makes themmore susceptible to nucleophillic attack than the corresponding carboxylic acids, and thus they

react vigorously at room temperature.

Ethanoyl chloride can be manufactured by treating ethanoic acid with phosphorus pentachloride.


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Water

The acid is reformed with the production of hydrochloric acid. This is a vigorous reaction, and

therefore acid chlorides must be used in anhydrous conditions.

CH3COCl + H2O CH3COOH + HCl

Ethanol

Esterification takes place, at a faster rate than with the acid and alcohol mixture.

CH3COCl + CH3CH2OH CH3COOCH2CH3+ HCl

Ammonia

Again,the ammonia substitutes for the chloride group to produce a primary amide. The HCl eliminatedthen reacts with excess ammonia.

CH3COCl + 2NH3CH3CONH2+ NH4Cl

Primary amines

The reaction with primary amines is basically the same, except that a secondary amide is

produced. Again, the HCl will react with excess amine, although this is not shown.

Ethylamine

CH3COCl + C2H5NH2CH3CONHC2H5+ HCl

Phenylamine:

Nitriles


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Nitriles are organic compounds where the chain is terminated by a CN group. The naming of the

nitrile includes the carbon that the nitrogen is bonded to, e.g. CH3CH2CN, propannitrile.

Reduction of nitriles is with hydrogen in the presence of a nickel catalyst. This gives a primary

amine. Other reduction mechanisms are possible, for example, lithium aluminium hydride

Hydrolysis of nitriles is carried out by refluxing with acid or akali. This proceeds through an

amide to the ammonium salt of the acid.

RCN RCONH2RCO2-NH4

+

In practice, stopping at the amide is not easy. The ammonium salt is not actually produced, but in

the case of acid hydrolysis, the ammonium salt of the mineral acid and the carboxylic acid. If

alkaline hydrolysis is carried out then ammonia is produced and the sodium salt of the acid

formed.

Amides

Amides can be used in synthesis to add the amino group onto a molecule. This can be done via a

degradation (the Hofmann degradation), leading to a compound with one less carbon atom, or via

dehydration to give an amine with the same number of carbon atoms.

Dehydration is carried out by heating with phosphorus(V) oxide (P4O10). This gives the

following reaction:

The product, a nitrile, can be reduced (e.g. with hydrogen and a nickel catalyst) to give an amine.

The Hoffman degradation is carried out using bromine and aqueous alkali:

RCONH2+ Br2+ 2NaOH RNH2+ CO2+ 2NaBr

Targeting Pharmaceuticals

This is to do with a balance between solubility in water / watery tissue and solubility in fat / fattytissue.

Hydrophilic - water loving Hydrophobic - water hating

Lipophilc - fat loving

To adjust the behaviour of a substance we adjust the functional groups attached.


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Hydrophilic functional groups

-OH, -CO2H, -NH2, -NH, -CONH These groups can hydrogen bond with water.

Lipophilic / hydrophobic functional groups

Alkyl groups and benzene rings - hydrocarbon groups

Solubility and retention time

If the substance is too lipophilic (insoluble):

1. It may not be sufficiently absorbed.2. Concentration in the bloodstream remains too low.

If the substance is too hydrophilic (soluble):

Retention time is too low - the substance is

quickly transported to the liver and broken down into soluble products, which are excreted viathe urine.

Both aspirin and oil of wintergreen have analgesic properties, but the different groups attached to

the benzene group give them different solubility properties. Aspirin is very soluble and dissolveseasily in the bloodstream. To make it more soluble and therefore easier to take the sodium salt

can be prepared - this converts back into the usual form in the acidic conditions in the stomach.

Oil of wintergreen is insoluble and is applied to the skin to relieve the pain of arthritis.


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Penicillin is an important drug that acts by preventing bacteria forming cell walls and thusreproducing. Its original form, penicillin G, was very soluble and rapidly excreted - lipophilic

side chains are added to make it less soluble. An even more soluble derivative, penicillamine,

can be formed, which complexes with heavy metals and is then excreted very rapidly, removing

the poisonous metals from the body. Co-ordination takes place with the marked lone pairs, using2 molecules to surround a metal ion.

Organic Preparations

Step 1 - Getting a reaction to occur

Unless other information is given, assume a 60% yield at this stage. The most expensive reagent should be used as the limiting factor - the other reagents

should be in excess.

If the reaction is an equilibrium then an excess of one reagent should be considered - it isalso helpful to remove the product(s) as they are produced.

Heating under reflux gives the highest possible temperature for that mixture in the liquidphase (the boiling point) without loss of product or reagent.

Heating methods:1. Direct heating with a bunsan burner

This is relatively rarely used in organic preparations as organic chemicals tend to

be highly flammable and the heat produced is not smooth.


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2. WaterbathThis is used for low temperatures (


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Liquids are purified as follows:1. Wash to remove impurities using a separating funnel. Release the pressure

regularly when shaking with a substance. Soluble impurities should be removedwith water, acid impurities with sodium carbonate and ethanol with calcium

chloride.

2.

Dry the liquid by standing it on anhydrous drying agent (may take up to 48hours). Drying agents commonly used are calcium chloride (not with alcohols),calcium oxide (often used with alcohols) and sodium sulphate.

3. Distillation completes the process, collecting the fraction that distils within 1Cof the boiling point of the liquid

Bayer Test, Dan Bromine Test

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