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

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 [r]

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 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 (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

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 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

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 (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

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 and (FIG 20.1.)

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

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 not involve delocalisation Polarisations which 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 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 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-)

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:

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 (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

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 positions. Other groups which similarly activate and 2,4,6-direct are: -OH, -OR, -NHR, -NR2, -C6H5, etc

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 and 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

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

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)

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 and (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

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 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-

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:

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

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

21.7.11 Other reactions

i) Oxidation: It is possible to make haloalkanes burn They so with a slightly smokey flame, but there is no residue More substituted alkanes like Bromochlorodifluoromethane (BCF) 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