21 21 1 introduction in chapters 21 and 22 we shall look at the reactions of different types of organic molecule we shall attempt to predict main reaction types from structure and then for each type

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21.1. INTRODUCTION

In chapters 21 and 22 we shall look at the reactions of different types of organic molecule. We shall
attempt to predict main reaction types from structure and then, for each type of molecule, we shall briefly
summarise reactions which do not easily fall into the 12 types described in the last chapter.

If you are unfamiliar with the types of molecule considered in these chapters, then chapter 27
(Nomenclature) should help. Look up each type of molecule as you consider its reactions.

Some indication of reaction conditions will be given. It is ridiculous to learn a whole list of conditions: if
they are needed for laboratory procedures they can be looked up.

However, reaction conditions also give an indication of the ease with which a reaction occurs. They
should certainly be absorbed at a sub-conscious level to help you acquire a feel for relative reactivities.
Once you have such a feel, you will be able to predict reaction conditions as accurately as can reasonably
be expected. If your examiners require more, they are wasting your time.

21.2. ALKANES

21.2.1. Predictions: Alkanes have no regions of either exposed nuclear charge or high electron density
and are therefore unaffected by either nucleophiles or electrophiles.

Moreover, there are no polarised bonds, so reactions occur homolytically, when they occur at all. In
addition, bonds are strong so reactive free radicals are needed to make alkanes react.

Finally, there are no multiple bonds, so addition is not possible. Nor is elimination favoured because this
would involve simultaneous attack on hydrogen atoms attached to two adjacent carbon atoms - an
unlikely event. The result of attack by free radicals on an alkane is therefore substitution i.e. the nett
reaction is homolytic substitution, via mechanism 1 (FIG. 20.1.).

21.2.2. Homolytic substitution in alkanes: examples of attacking free radicals:

21.2.3.
Other
reactions:
Two other
homolytic
reactions
undergone
by alkanes
are cracking
and

combustion.
These are not
chain

reactions, but like homolytic substitution, the conditions needed for reaction are extreme, i.e. high
temperature:

i) cracking: The bonds break rather randomly in cracking reactions, producing a mixture of saturated and
unsaturated hydrocarbons.

Table 21.1. Examples of free radical substitution in alkanes (see section 20.3 for
mechanism)

Radical Reagent Conditions Product(s)

lCl chlorine gaseous and UV

light

or in CCl4

chloroalkane, dichloroalkanes etc

lBr bromine gaseous/heat/UV bromoalkane, dibromoalkanes etc

lSO2.OH fuming sulphuric acid heat alkanesulphonic acid (salts =

detergents)

lNO2 concentrated nitric

acid

heat/gas phase nitroalkanes (mixture due to fission

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... ...400 - 700°C

2CH3CH2CH3(g)...g... CH4(g) + CH2=CH2(g) + CH3CH=CH2(g) + H2(g)

...C-C bond fission... dehydrogenation
ii) combustion:

CH4(g).... +.... 2O2(g)....g.... CO2(g).... +.... 2H2O(g)

2C2H6(g).... +.... 7O2(g)....g.... 4CO2(g).... +.... 6H2O(g)

Note that combustion is an oxidation reaction. Alkanes may also undergo "autoxidation", by a free radical
chain mechanism. This can be initiated by light, or an "initiator". Typical initiators are substances which
produce free radicals, sometimes at higher temperatures or in the presence of light. Autoxidation is a bad

term because it implies that the process takes place in the absence of any other reactant. In fact, the
oxidising agent is atmospheric oxygen.

21.3. ALKENES

21.3.1. Predictions i) The double bond in alkenes is a region of high electron density which therefore
attracts electrophiles. Moreover, the molecule is unsaturated and the attack results in addition. i.e. nett
reaction is electrophilic addition (by mechanisms 8 and 9).

However, the implied connection between unsaturation and addition begs the question, "What favours
saturation over unsaturation?"

The answer is illustrated in the equation below. The electrons involved in the bonds resulting from
addition (bonds iii, iv and v), are held more tightly than they were before addition occured (bonds i and
ii); electrons are pulled away from the double bond and the Br-Br bond, into single bonds where they are

held more tightly.

The relative tightness with which the electrons are held before and after addition can be understood in the
following way. The pair of electrons in the p orbitals of double bond (i) are not particularly close to the
two carbon nuclei. They become more strongly held in the two s bonds (iii and v) since these are directly
inbetween the carbon and bromine nuclei.

Moreover, the two electrons in bond (ii) between two large bromine atoms, become more tightly held in
bonds (iii) and (v), where the smaller size of the carbon atoms makes the bonding electrons closer to the
nuclei.

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Table 21.2. Examples of electrophilic addition to alkenes.

Electrophile reagent conditions main product(s)

d+..

d-*Br-Br *Bromine tetrachloromethane, r.t.

-CHBr-CHBr-†Br-OH †Brominein water, room temp. Water

-CHBr-CHOH-plus
some-CHBr-CHBr-The observable disappearance of

brown colour makes this
reaction useful as a test for

double bonds.

**H-Hal H-Hal gaseous -CH2

-CHHal-H-OH catalysedacid

room temp., some alkenes
Industrially high temp and press

used. E.g. ethanol using silcon
dioxide coated w. H3PO4 as

catalyst (see also method below)

-CH2

-CHOH-H-OSO3H

conc.
sulphuric

acid

room temperature

-CH2-CHOSO3

H-Boiling the product with water
gives alcohols by nucleophilic

substitution, an important
industrial process. 85%
sulphuric acid at 0°C is used for

the addition stage.
*Or chlorine (faster than bromine) or iodine (v.v.slow). (Fluorine reacts differently and

explosively with ethene to give carbon and HF gas.)
†Or chlorine, or iodine.

** reaction rate: HF << HCl < HBr < HI (Can you explain?)

21.3.3. Predictions ii) The above reactions occur in the absence of conditions which produce free
radicals. In conditions where free radicals are present (see section 20.12.1.) addition may occur via a
homolytic mechanism, i.e. homolytic addition via mechanism 6 (FIG. 20.1.).

Reactants which may add homolytically include: *Br-H (not HCl or HI), RS*-H, Cl3C*-Cl, and Cl3C*-H.

* indicates the part of the molecule which forms the initial attacking radical.

Polymerisation by a homolytic addition mechanism has already been discussed in section 20.12.2.

21.3.4. Another example of homolytic addition, but not a chain reaction, is the reduction of alkenes by
hydrogen gas in the presence of a metal catalyst such as platinum, or finely powdered nickel.

...Pt/200°C

-CH=CH-... +... H2...g... -CH2-CH2

-...fine Ni/r.t.

The binding sites on the nickel for hydrogen atoms are slightly further apart than the length of the H-H
bond. This tends to split the hydrogen into reactive atoms. Hydrogenation of double bonds is an important
process in the manufacture of some margarines. Saturated fats tend to be more solid than unsaturated oils,
though the health implications are well known.

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i) Oxidation:
a) Combustion:

CH2=CH2(g)... +... 3O2(g)...g... 2CO2(g)... +... 2H2O(g)

b) With acidified potassium manganate (VII) solution:
...cold dil.

-CH=CH-... +... H2O... +... [O]...g...

-CH-CH-...KMnO4... |.... |

...OH .OH

Note that this reaction involves a readily observable change. The purple colour of the manganate (VII)
disappears, and brown manganese (IV) oxide is precipitated.

c) With ozone:

...O-O
...\... / ...e.g. CCl4... \ /.... \ /

...C=C... +... O3...g... C... C

.../... \... solution... / .\ .../. \
...O
...an ozonide

Ozonides are explosive and are not isolated. However, hydrolysis of the ozonide is a useful reaction. It
produces carbonyl compounds (provided a reducing agent such as zinc dust and ethanoic acid is present
to prevent oxidation of the carbonyls by the hydrogen peroxide):

...O-O... H2O

...\ /... \ /... r.t./warm... \... /

...C... C...g... C=O... +... O=C... +... H2O2

.../. \... /. \ ...Zn/HEt... /... \
...O

The overall reaction with ozone, followed by hydrolysis, is known as ozonolysis and its usefulness lies in
its power as an analytical tool:

analysis of the resultant carbonyls gives information about the structure of the parent alkene. For
example, what alkene would produce a mixture of propanone and ethanal on ozonolysis?

21.4. ALKYNES

21.4.1. Predictions i) The arguments are similar to those for alkenes. The triple bond in alkynes is a
region of high electron density which therefore attracts electrophiles. Moreover, alkynes are unsaturated
and attack results in addition. The nett reaction is therefore electrophilic addition via mechanisms 8 and
9 (FIG. 20.1.).

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Note also, that after addition to a triple bond, there is still a double bond. This may undergo further
electrophilic addition. However, reactivity may be less than expected if the first addition to the triple bond
has introduced, say, a halogen atom into the molecule:

A halogen atom attached to a doubly bonded carbon atom has a negative inductive effect (section 21.5.).
This reduces the electron density in the double bond and makes it less susceptible to electrophilic attack
than a double bond in a simple alkene. Moreover, further addition will be directed as predicted by
Markownikoff's rule (section 20.14.1.).

21.4.2. Examples of electrophilic addition to alkynes

The electrophiles which add to alkynes are largely the same as those which add to alkenes (table 21.2.),
and in the absence of free radicals, the main product is predicted by Markownikoff's rule. However,
remember that alkynes are generally less reactive than alkenes and:

(i) Bromine water does not react.

(ii) the addition of halogens or halogen halides requires a halogen carrier catalyst such as FeBr3.

Alternatively, UV light enables the reaction to proceed via a homolytic mechanism. However, under these
conditions, the reaction with chlorine may be explosive, producing carbon and hydrogen chloride.

(iii) addition of water under acid conditions requires mercury (II) sulphate to further catlyse the process.
The method used is bubbling the alkene into hot dilute sulphuric acid containing the catalyst. The "enol"
so produced is unstable and rapidly undergoes rearrangement to form a carbonyl compound. For example:

The reaction is useful in the synthesis of a large range of organic compounds, especially when it is
considered that carbon itself may be the starting point, via calcium(II) dicarbide!

... 2000°C

CaO(s).... +.... 3C(s)...g... CaC2(s).... +.... CO(g)

CaC2(s).... +.... 2H2O(l)...g... Ca(OH)2(s).... +.... CH=CH(g)

21.4.3. Predictions ii) Apart from electrophilic addition there is another fascinating property of alkynes.
Electrons in an sp1 orbital are closer to the nucleus than those in an sp2 orbital, and even closer than those

in an sp3 orbital. Under certain conditions, a hydrogen next to a triple bond can actually be removed as a

proton and the C-H bonding electron pair accomodated in the carbon atom's sp1 orbital. Thus a carbanion

is formed and the alkyne can be regarded as having slight acidic properties (section 21.4.4.).
21.4.4. Acidic properties. The acidic properties are shown in two ways:

i) The amide ion is a strong enough base to remove the acidic hydrogen. The reagent is sodium dissolved

in liquid ammonia.

2NH3(l).... +.... 2Na(s)...g... 2Na+ -:NH2(am).... +.... H2(g)

-C=C-H(g)... -NH

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Sodium alkynides are extremely useful for the synthesis of other alkynes because the alkynide ion is a
powerful nucleophile in reaction with haloalkanes (section 21.7.2.).

(ii) Also, alkynes with terminal hydrogen atoms form silver and copper(I) salts when treated with
diammine complex ions of the metals. The formation of characteristic precipitates makes the reactions
useful tests for 1-alkynes:

RC=CH(g) + Cu(NH3)2+(aq) + -OH(aq)...g... RC=CCu(s) + H2O(l) + NH3(aq)

...red ppt.

RC=CH(g) + Ag(NH3)2+(aq) + -OH(aq)...g... RC=CAg(s) + H2O(l) + NH3(aq)

...white ppt.
21.4.5. Other reactions

i) Oxidation: Like alkanes and alkenes, alkynes undergo various oxidation reactions, not least
autoxidation and combustion.

E.g. Combustion: 2CH=CH(g)... +... 5O2(g)...g... 4CO2(g)... +... 2H2O(g)

21.5. INDUCTIVE AND MESOMERIC EFFECTS

21.5.1. Introduction: In section 21.4.1. a new concept was slipped into the text without explanation.

What is a negative inductive effect? For that matter, what is a positive inductive effect? Briefly, inductive
effects, positive or negative, are little more than polarised bonds seen with a different journalistic bent. It
is important to realise that even scientific language depends on the attitude of the observer.

Inductive effects exist in s-bonds and also in p-bonds, but in the former case they do not involve
delocalisation. Polarisations which do involve delocalisation via p bonding systems and p-orbitals are
known as mesomeric or conjugative effects.

In fact, mesomeric and conjugative effects are little more than delocalisation seen with a different
journalistic bent. They do not even involve polarisation in all circumstances.

Two further points on language: First, the different jounalistic bent described above is not totally
artificial. It is useful for describing particular situations because it saves clumsy explanations. Good
scientists would not make good Sun reporters, though they might do well on The Independent.

Second, inductive and mesomeric effects are often talked about as "occurring". This does not mean that
they occur on any time scale. The negative inductive effect of a halogen atom does not suddenly happen
in a haloalkane; it is there all the time.

21.5.2. Inductive effects exist where (occur where) two atoms or groups which differ in electronegativity
are bonded.

A more electronegative atom or group exerts a negative inductive (-I) effect, "pulling" electrons towards
itself and acquiring partial negative charge (d-).

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The most important groups to exert an electron pushing, or +I, effect are alkyl groups. This is largely a
characteristic of the large number electropositive hydrogen atoms within alkyl groups.

21.5.3. Mesomeric or conjugative effects exist:

i) where p-bonding systems would otherwise be next to each other - separated by one single bond, or
ii) where electrons in p-orbitals would otherwise be next to p-bonding systems - separated by one single
bond.

The term conjugation is often reserved for situations where the polarity of the effect is not relevant, eg in
buta-1,3-diene (section 4.8.8.) The double bonds which appear in the simple bonding diagram (FIG.
4.13.) are conjugated and there is no polarisation. However, in phenylethene, it is more relevant to think
of the ethene group exerting a positive mesomeric (+M) effect on the benzene ring. The p-bonding
systems are conjugated, but in this case there is polarisation:

Another way of describing the situation is to say that electrons from the alkene double bond are
delocalised into the benzene ring.

In phenylethanal, the carbonyl group is considered as exerting a negative mesomeric (-M) effect on the
benzene ring. Electrons are delocalised out of the ring onto the electronegative oxygen atom:

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densities of the p-bonding systems which overlap i.e. electrons delocalise from regions of higher electron
density to regions of lower electron density, as in the case of phenylethene described above.

21.5.4. Positive or negative? In the last section we described a positive mesomeric effect in
phenylethene; the ethene group exerts a positive mesomeric effect on the benzene ring. However, it would
appear just as valid to say that the benzene ring exerts a negative mesomeric effect on the carbonyl group.
Which is correct?

Sometimes, either can be correct. Take phenylethene: If you are considering the reactions of the ethene
group, it is probably most useful to think in terms of the benzene ring exerting a -M effect on the ethene
group. If you are considering the reactions of the benzene ring, it is probably most useful to consider how
the +M effect of the ethene group affects the benzene reactions.

Alternatively, using the other form of language, "electrons from the double bond are delocalised into the

benzene ring", covers both situations.

In other cases when using the mesomeric terminology, one description certainly is better than the other.
Thus in phenylethanal it would be artificial to describe the benzene ring exerting a positive mesomeric
effect and "pushing" electrons onto the electronegative oxygen atom.

Similar arguments apply to inductive effects.

21.6. BENZENE AND OTHER AROMATIC HYDROCARBONS

21.6.1. Predictions. The high electron density of the benzene ring's p-bonding system makes it
susceptible to attack by electrophiles. However, despite being unsaturated, benzene does not undergo
addition as a result of such attack.

Addition would involve a concentration of the electron density within the benzene ring by breaking the
aromatic delocalisation:

Thus substsitution of a hydrogen by the attacking group is favoured, since this restores delocalisation. 
The overall reaction is therefore elctrophilic substitution via mechanism 5 (FIG. 20.1.).

21.6.2. Electrophilic substitution in the benzene ring: some examples.
Table 21.3. Examples of electrophiles which react with benzene.

Electrophile reagent conditions main organic products
NO2+

conc. nitric
dissolved in
conc. sulphuric

55°C g
100°C g
reflux 48hrs g

nitrobenzene
1,3-dinitrobenzene
1,3,5-trinitrobenzene

*SO3 conc. sulphuricacid 80°C Benzenesulphonic acid

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Cl-Cl--AlCl3

Br-Br--FeBr3

R-Hal--AlCl3

chlorine g
bromine g
haloalkane g

catalyst (or iron
filings g FeBr3)

(Lewis acids)

g chlorobenzene
g bromobenzene

g alkylbenzene, but difficult to stop at
mono substituted stage

..*

RCO-Cl--AlCl3 acid chloride

Lewis acid halogen
carrier, as above.

phenylketone (mono!) can be reduced
to corresp. alkyly deriv. eg by Zn
amalgam/HCl.

CH3=CH2 ethene

acid to protonate
alkene,

(HCl/H3PO4), plus

Lewis acid

ethylbenzene (mono!) Industrially:
+Zn/600°C g phenylethene (styrene)
* marks the electron deficient centre in the electrophile (if not already obvious).

21.6.3. Effects of the rest of the molecule. The table shows that it is easy to stop some reactions at the
mono substitution stage, but difficult to stop others. This highlights an interesting piece of theory.
Electron pushing and electron withdrawing groups attached to the benzene ring affect its reaction with

electrophiles in two ways:

i) they make it either more reactive (activate) by increasing electron density in the ring, or less reactive
(deactivate) by decreasing the electron density in the ring;

ii) they direct electrophiles to particular positions in the ring by changing the distribution of electron
density i.e. by making it more concentrated around particular carbon atoms. Electrophiles are more likely
to attack in these positions.

Looking at this in more detail emphasises a point about models. It is easiest to see how these effects come
about by using a model of the benzene ring which looks less like the real thing than the model which
shows delocalisation. Models are only models and, as previously stated, different models serve different
functions.

21.6.4. Positive mesomeric effects e.g. NH2 group.

i) Electron pushing groups activate the ring towards electrophilic attack because the electron density is
increased.

ii) They are also 2,4,6-directing because the electron density is increased more in the 2,4 and 6 positions.
Other groups which similarly activate and 2,4,6-direct are: -OH, -OR, -NHR, -NR2, -C6H5, etc.

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i) Electron withdrawing groups deactivate the ring towards electrophilic attack because the electron
density is decreased.

ii) They are also 3,5-directing, because the electron density is reduced less in the 3 and 5 positions
positions.

Other groups which similarly deactivate and 3,5-direct are: -COOH, -NO2, -C=N, -SO3H, etc.

21.6.6. Inductive and combined effects

The same effects can be brought about by inductive mechanisms. The most important groups to exert a
positive inductive effect on the ring are alkyl groups:

Groups which exert a negative inductive effect are -CF3, -CCl3 etc.

Obviously, +I effects activate and 2,4,6-direct, and -I effects deactivate and 3,5-direct. However, some
groups exert both mesomeric and inductive effects. In the case of the nitro group this is simple: it exerts
both a -M and a -I effect.

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21.6.7. Summary of effects of benzene ring substituents on electrophilic attack.
Table 21.4. The effects of substituents on electrophilic substitution into the benzene ring.

2,4,6-directing 3,5-directing

strongly activating

-NH2, -NHR, -NR2, -OH

moderately activating

-NHCOCH3, -NHCOR, -OCH3, -OR

weakly activating
-CH3, -C2H5, -R, -C6H5

weakly deactivating
-Cl, -Br, -I

moderately deactivating

-SO3H, -COOH, -CHO, -C=N

strongly deactivating
-NO2, -CF3, -CCl3

These effects are important to consider when:

i) Predicting the main products when benzene and its derivatives react;
ii) predicting reaction conditions;

iii) choosing methods to synthesise benzene derivatives
....and so on.

21.6.8. Other reactions

i) Addition. Extreme conditions are needed to enable addition to the benzene ring, in particular, the
presence of free radicals eg:

...U.V.

C6H6... +... 3Cl2...g... C6H6Cl6

...Ni. cat.

C6H6... +... 3H2...g... C6H12

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a) Benzene undergoes combustion in air to produce Carbon dioxide and water.
2C6H6... +... 15O2...g... 12CO2... +... 6H2O

However, combustion of aromatic compounds is incomplete, giving a smokey black flame due to
production of carbon. In qualitative analysis, the smokey flame is often taken as an initial indication that
an aromatic, or highly unsaturated, compound is present.

b) The controlled catalytic oxidation of methyl benzene by air (diluted with nitrogen to prevent further
oxidation to benzenecarboxylic acid) is used to make benzenecarbaldehyde.

c) A reaction of some industrial importance is the controlled catalytic oxidation of benzene by air to
butenedioic (maleic) anhydride used in making varnishes and lacquers.

d) Benzene reacts with ozone at room temperature:
...3H2

C6H6... +... 3O3...g... C6H6(O3)3...g... 3(CHO)2... +... 3H2O

...Zn/HEt

e) Any side chain connected to the benzene ring via a carbon atom is oxidised by refluxing with acid or
alkaline potassium manganate(VII), or acidified potassium dichromate(VI), or dilute nitric(V) acid etc.
Whatever the side chain, it is always oxidised to -COOH. E.g.

21.6.9. Methylbenzene (Toluene)

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i) The methyl group activates the ring towards electrophiles, and 2,4,6-directs (section 21.6.2)

ii) The side chain undergoes its own reactions such as the oxidation described in section 21.6.8.iie above,
as well as reactions typical of alkanes described in section 21.1.

21.7. HALOALKANES

21.7.1. In this section we shall break the pattern of dealing completely with each prediction in turn. This
is because the different types of reaction are in such close competition, they must be considered together.
21.7.2. Predictions i) Halogen atoms are electronegative and attract the bonding electrons towards
themselves and away from the atoms to which they are bonded. In haloalkanes, this exposes nuclear
charge on the functional carbon atom:

...d+...
d-...RCH2-Hal

As a result, the carbon atom is susceptible to attack by nucleophiles. Moreover, the electronegative
halogen atom is able to acquire total control of the bonding electrons. This occurs as a pair of electrons
from the nucleophile forms a new bond with the functional carbon. Attack therefore results in
substitution and the overall reaction is nucleophilic substitution via mechanisms 2 and 3 (FIG. 20.1.).
The reactivity of the haloalkanes to nucleophilic substitution decreases in the order I > Br > Cl (>F). This
order of reactivity is paralleled by the order of C-Hal bond lengths and bond strengths (section 22.2.2.).
21.7.3. Predictions ii) But there is another possibility. The halogen is a good "leaving group" for the
reason stated above, but it may not always be substituted. Sometimes, the attacking species pulls a
hydrogen atom off a carbon next to the functional carbon atom. In such a case, it is acting as a base rather
than a nucleophile. The overall reaction is therefore elimination via mechanisms 10 and 11 (FIG. 20.1.).
21.7.4. Elimination vs. substitution:The balance between elimination and nucleophilic substitution is 
affected by three factors:

...i) the attacked species,
...ii) the attacking species, and
...iii) the "external" conditions.

i) Attacked species: The more branching that exists around the functional carbon atom in the attacked
species, the more difficult it is for an attacking base/nucleophile to reach this exposed nuclear charge.
Thus elimination becomes less likely in the series:

...3°... 2°... 1°
..R... R

...\... \

R-C-Hal... >... CH-Hal... >... R-CH2-Hal

.../... /
..R... R

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Thus elimination becomes less likely in the series:

-OR > -OH > RNH

2 > NH3 d -CN > NO2- > NO3- > F- > Cl- > Br- > I

-iii) External conditions: Higher temperatures encourage the formation of smaller molecules and
elimination is thus favoured by higher temperatures. (chapter 12).

21.7.5 Unimolecular vs. bimolecular: However, not only do we have to decide between substitution and
elimination, we have to decide whether the reaction occurs via a unimolecular or a bimolecular
mechanism. Again there are three factors to consider:

i) Attacked species: Unimolecular mechanisms become less likely in the series: tertiary > secondary >
primary. This can be predicted because the intermediate carbonium ions on the unimolecular pathway are
decreasingly "stabilised" in this order by positive inductive effects:

i.e. the ions become decreasingly easy to form in this order because their formation involves more
concentration of charge i.e. more pulling away of electrons from nuclear control.

ii) Attacking species: Unimolecular mechanisms are more likely to occur with weaker nucleophiles and
bases. These give the attacked molecule time to split into ions.

iii) External conditions: Unimolecular mechanisms are favoured by polar conditions/solvents which
solvate the intermediate ions i.e. attraction of the ions by solvent molecules encourages their formation.
21.7.6. Nett effect of above factors

Given all the factors which determine the reaction of a haloalkane with nucleophiles/bases, it is hardly
surprising that more than one type of reaction is likely to occur in a given set of conditions. It is often
very difficult to predict the main course of reaction and therefore difficult to predict the main product - if
there is one which majors.

The scheme below summarises the reactions of halogenoalkanes with potassium hydroxide.
Two variables are considered:

...i) branching next to the functional carbon, and

...ii) type of solvent (varying from pure water to pure.ethanol via a
...continuous range of mixtures).

The variation of solvent itself has two effects:
...first, water is more polar than ethanol;

...second, ethanol favours the formation of an extremely strong base,
...the ethoxide ion CH3CH2O-.

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haloalkane: ... primary ... secondary ... tertiary
main reacn. type:. ...SN2...(E2) ... SN1... SN2... E2 ... SN1.... E1.... (E2)

In predicting this pattern, it is useful to have these starting points in you reasoning:

i) Substitution is more likely than elimination, and bimolecular mechanisms are more likely than
unimolecular mechanisms.

ii) With primary and tertiary haloalkanes the nature of the haloalkane is a stronger factor than the nature
of the solvent. Changes in solvent can be regarded as moving the course of reaction away from the most
characteristic type, i.e. away from SN2 for primary haloalkanes, and away from E1 for tertiary

haloalkanes.

iii) With secondary haloalkanes the type of solvent is a stronger factor than the nature of the haloalkane.
When the solvent is least influential (a mixture of water and ethanol), the reaction is SN2.

21.7.7. Nucleophilic substitution in haloalkanes: examples of nucleophiles.
Table 21.5. Nucleophiles which react with haloalkanes

Nucleophile Reagent Conditions Main organic product

-OH/H
2O

Water, or
KOH/NaOH in
water/ethanol.

Depend on particular
haloalkane. Attack by water
catalysed by Ag2O

Corresponding alcohol E.g.
bromoethane gives ethanol

:NH3 Ammonia in water/ethanol Again vary. Typical: 100K in sealed tube i.e. pressure

g Corresp. 1° g amine 2° g
amine 3° g amine 4°

ammonium salt. E.g. C2H5Br

g C2H5NH2 g (C2H5)2NHg

(C2H5)3N g (C2H5)4N+Br

-amines see reaction with ammonia above

-CN KCN in

water/ethanol reflux

Corresp. nitrile. E.g.
bromoethane gives
ethanonitrile

-NC Silver salt treat with moist salt Corresp. isonitrile

RCOO

-Sodium salt in
water, or

Silver salt

reflux

treat with moist salt

Ester. E.g. Bromoethane

gives RCOOC2H5

RO- Sodium salt in

ethanol reflux

Ether. E.g. Bromoethane
gives ROC2H5

NO2- Silver salt treat with moist salt Mixture of corresp. nitrite and nitroalkane

NO3- Silver salt treat with moist salt Corresp. alkyl nitrate

"R-" *Grignard reagent In DRY ether Alkane. E.g. Bromoethane

gives RC2H5

Notes:

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though often needs gentle warming with the hands to get it going. Alternatively, a crystal of iodine may
be needed to start the reaction off.

...dry ether

R-Hal... +... Mg...g... "RMgHal"

Once the reaction is going, it must be controlled by adding the haloalkane in only small amounts. Also, a
water-cooled reflux condenser must be used to prevent ether fumes from being lost (FIG. 23.3.).

The value of Grignard reagents is that they react as if they had the structure R-MgX+ in ethereal solution

(from which they are not usually isolated). Thus they are effectively a source of carbanion nucleophiles,
and as such are extremely useful in synthetic reactions (section 23.4.).

21.7.8. More effects of the rest of the molecule

The most dramatic effect on nucleophilic substitution occurs when the halogen atom is attached directly
to a benzene ring or a doubly/triply bonded carbon atom. Chlorobenzene, for example, is extremely
resistant to nucleophilic substitution. It requires treatment with concentrated sodium hydroxide at 300°C
under pressure in order to undergo hydrolysis (i.e. to undergo nucleophilic substitution of the -Cl by
-OH).

The reason is that the high electron density of the benzene ring prevents attack by nucleophiles on the
functional carbon atom. Moreover, delocalisation of a chlorine lone pair into the benzene ring further
increases the electron density around the carbon. It also gives the C-Cl bond partial double character

making it more difficult to break.

The arguments are similar for halogens attached to doubly bonded and triply bonded carbon atoms.
In contrast, when the functional carbon is one removed from the benzene ring or multiple bond the high
electron density of the p-bonding system exerts a +I effect about equivalent to that in a secondary
haloakane.

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When discussing the relative reactivities of organic halogen compounds, an essential factor is usually
completely ignored. The reactivity of a particular organic halogen compound depends on which
mechanism of reaction it undergoes (SN1 or SN2). It is therefore also dependent on the other factors which

determine the mechanism.

i) In SN1 reactions the rate determining step is the formation of the carbonium ion. The readiness with

which this occurs can be predicted from information about the activation energy. This in turn can be
gleaned from consideration of the relative stabilities of the intermediate carbonium ions.
Benzenecarbonium ions, and alkenecarbonium ions are particularly stable because concentration of the
positive charge is reduced by delocalisation of electrons from the p-bonding systems. E.g.

The order of decreasing SN1 reactivity in a series of haloalkanes (as predicted from the relative stabilities

of the intermediate carbonium ions) is therefore:

C6H5-CH2-Hal > RCH=CH2-CH2-Hal > R3C-Hal > R2CH-Hal > RCH2-Hal

ii) In contrast SN2 reactivity decreases in the order

primary > secondary > tertiary haloalkane.

This is because alkyl groups attached to the functional carbon atom sterically hinder attack by the
nucleophile. Benzene rings or mutiple-bonded groups one removed from the functional carbon offer little
steric hindrance, though they may reduce the partial positive charge on the functional carbon.

An additional complication is that the order primary > secondary > tertiary is changed when the alkyl
groups are themselves branched thus sterically hindering approach by nucleophiles. Thus

1-chloro-2,2-dimethylypropane, a primary haloalkane, is very unreactive.

21.7.10. A final comment on equilibrium

In section 21.7.4.ii., we referred to a relative order of nucleophilic strength. It is tempting to suggest that
strong nucleophiles will completely replace leaving groups that would make weak nucleophiles. This is

not so. For one thing, good nucleophiles are often good leaving groups (e.g. I-). Moreover, these terms

usually refer to rates of reaction.

Thus, in a given nucleophilic substitution reaction, there is another important factor to bear in mind when
deciding how good the yield will be: the reaction usually starts far from equilibrium. So, the reaction
usually starts with high concentrations of organic reactant and particularly of nucleophile, but zero
concentration of products. Even with a good yield of product, the reaction may still be far removed from
equilibrium.

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21.7.11. Other reactions

i) Oxidation: It is possible to make haloalkanes burn. They do so with a slightly smokey flame, but there
is no residue. More substituted alkanes like Bromochlorodifluoromethane (BCF) do not burn, and are
used in fire extinguishers, though they may give toxic by-products during use.

ii) Reduction: Haloalkanes, and particularly iodoalkanes, may be reduced to the corresponding alkane by
the powerful reactant, hydrogen iodide:

R-I... +... HI...g... R-H... +... I2

iii) With sodium: Alkyl chains may be linked tohether by reaction of haloalkanes with sodium in dry
ether:

2RHal... +... 2Na...g... R-R... +... 2NaHal

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