2. Chemical - IJCPT- Survey on Alkyl Halide Compounds

8/20/2019 2. Chemical - IJCPT- Survey on Alkyl Halide Compounds

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10

Impact Factor (JCC): 3.5367

Primary, secondary and tert

Different Representations of Vinyl Io

Properties of Alkyl Halide

The alkyl halides are at best o

break attractions between the halogen

break the hydrogen bonds between wat

Na

Index

Figure 2

iary alkyl halides (X = F, Cl, Br, or I)

Figure 3

dide

Figure 4

Figure 5

nly slightly soluble in water. For a halogenoalkane to

alkane molecules (van der Waals dispersion and d

r molecules. Both of these cost energy.

gham Mahmood Aljamali

opernicus Value (ICV): 3.0

dissolve in water you have to

ipole-dipole interactions) and


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Survey on Alkyl Halide Compounds

www.tjprc.org

Energy is released when new

will only be dispersion forces and dip

water, and so not as much energy is rel

sufficiently "unprofitable" that very littl

Primary Alkyl Halides

In a primary (1) halogenoalka

group.Some examples of primary alkyl

Notice that it doesn't matter h

an alkyl group from the CH2 group hol

are often counted as primary alkyl hali

it.

Secondary Alkyl Halides

In a secondary (2) halogenoa

groups, which may be the same or diffe

Tertiary Alkyl Halides

In a tertiary (3) halogenoalka

which may be any combination of same

Preparation of Alkyl Halide

• By Reaction of Alcohols: wit

attractions are set up between the halogenoalkane a

le-dipole interactions. These aren't as strong as the o

ased as was used to separate the water molecules. T

e dissolves.

ne, the carbon which carries the halogen atom is on

halides include:

Figure 6

w complicated the attached alkyl group is. In each ca

ing the halogen. There is an exception to this: CH3B

es even though there are no alkyl groups attached to t

lkane, the carbon with the halogen attached is join

rent. Examples:

Figure 7

e, the carbon atom holding the halogen is attached

or different. Examples:

Figure 8

thionyl chloride or with phosphoryl chloride

11

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d the water molecules. These

riginal hydrogen bonds in the

e energetics of the change are

ly attached to one other alkyl

se there is only one linkage to

r and the other methyl halides

he carbon with the halogen on

d directly to two other alkyl

directly to three alkyl groups,


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• By Addition HX: to double o

• By Reaction of HX with N-

Alkyl Halide Reaction

Na

Index

Figure 9

trible bond :

Figure 10

romo Succinamide

Figure 11

Figure 12

Figure 13




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Na

Index

Figure 18

Figure 19

Figure 20




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Survey on Alkyl Halide Compounds 15

[email protected] www.tjprc.org

Examples

Figure 21

Figure 22

Electrophile: An electron deficient atom, ion or molecule that has an affinity for an electron pair, and will bond to

a base or nucleophile.

Nucleophile: An atom, ion or molecule that has an electron pair that may be donated in forming a covalent bond

to an electrophile (or Lewis acid).

If we use a common alkyl halide, such as methyl bromide, and a common solvent, ethanol, we can examine the

rate at which various nucleophiles substitute the methyl carbon. Nucleophilicity is thereby related to the relative rate of

substitution reactions at the halogen-bearing carbon atom of the reference alkyl halide. The most reactive nucleophiles are

said to be more nucleophilic than less reactive members of the group. The nucleophilicities of some common Nu:(–

) reactants vary as shown in the following

Nucleophilicity

CH3CO2(–) < Cl(–) < Br(–) < N3(–) < CH3O(–) < CN(–) ≈ SCN(–) < I(–) < CH3S(–)

E1 and E2 Mechanism

A molecule with the halogen substituted with something else, one can completely eliminate both the halogen and

a nearby hydrogen, thus forming an alkene by dehydrohalogenation. For example, with bromoethane and sodium

hydroxide (NaOH) in ethanol, the hydroxide ion HO− abstracts a hydrogen atom. Bromide ion is then lost, resulting

in ethylene, H2O and NaBr. Thus, haloalkanes can be converted to alkenes


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• The E2 Reaction

We have not yet considered

presented at the beginning of this sectio

(CH3)3C-Br + CN(–) ——> (

We know that t-butyl bromide

not sufficiently polar to facilitate an SN

decent base, being about ten times wea

plausible reaction remaining for this c

consider the reaction of a 2º-alkyl halid

SN1 and SN2 Mechanism

Where the rate-determining s

reaction. In this case, the slowest (th

carbocation and the halide anion. The n

SN1 reactions are associated

attacked from either face. They are fa

charge on the carbocation by three el

sterically bulky, hindering the SN2 mec

As the number of substituents

approach of the incoming nucleophile a

In the case of a tertiary alkyl h

nucleophile. This is called a SN1 reacti

Na

Index

the factors that influence elimination reactions, suc

n.

H3)2C=CH2 + Br(–) + HCN

is not expected to react by an SN2 mechanism. Furt

1 reaction. The other reactant, cyanide anion, is a go

er than bicarbonate. Consequently, a base-induced el

ombination of reactants. To get a clearer picture of

, isopropyl bromide, with two different nucleophiles.

tep of a nucleophilic substitution reaction is unimol

us rate-determining step) is the heterolysis of a ca

ucleophile (electron donor) attacks the carbocation to

ith the racemization of the compound, as the trigon

vored mechanism for tertiary haloalkanes, due to th

ectron-donating alkyl groups. They are also preferr

hanism

around the carbon centre undergoing reaction increa

nd consequently an SN2 mechanism becomes less fav

Figure 23

alide, loss of the halide occurs first to give a carbocat

n (Substitution, Nucleophilic, first order ).

Figure 24



h as example 3 in the group

ermore, the ethanol solvent is

d nucleophile; and it is also a

imination seems to be the only

the interplay of these factors

ecular, it is known as an SN1

rbon-halogen bond to give a

give the product.

al planar carbocation may be

e stabilization of the positive

d where the substituents are

ses, the substituents block the

urable.

ion which then reacts with the


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Examples

Figure 25

Figure 26

Table 1

Nucleophile Anionic Nucleophiles

(Weak Bases: I–, Br–,

SCN–, N3–,

CH3CO2–, RS–, CN– etc. )

pKa's from -9 to 10 (left to

right)

Anionic Nucleophiles (

Strong Bases: HO–, RO)

pKa's > 15

Neutral Nucleophiles

( H2O, ROH, RSH, R3N )

pKa's ranging from -2 to 11Alkyl Group

PrimaryRCH2–

Rapid SN2 substitution. The

rate may be reduced bysubstitution of β-carbons,

as in the case of neopentyl.

Rapid SN2 substitution. E2

elimination may also occur.e.g. ClCH2CH2Cl + KOH

——> CH2=CHCl

SN2 substitution. (N ≈ S >>O)

SecondaryR2CH–

SN2 substitution and / or E2

elimination (depending on

the basicity of thenucleophile). Bases weaker

than acetate (pKa = 4.8)give less elimination. The

rate of substitution may be

reduced by branching at the

β-carbons, and this will

increase elimination.

E2 elimination willdominate.

SN2 substitution. (N ≈ S >>O)In high dielectric ionizing

solvents, such as water,

dimethyl sulfoxide &

acetonitrile, SN1 and E1products may be formed

slowly.

TertiaryR3C–

E2 elimination willdominate with most

nucleophiles (even if they

are weak bases). No SN2substitution due to steric

hindrance. In high

dielectric ionizing solvents,

such as water, dimethyl

sulfoxide & acetonitrile,SN1 and E1 products maybe expected.

E2 elimination will

dominate. No SN2

substitution will occur. Inhigh dielectric ionizing

solvents SN1 and E1

products may be formed.

E2 elimination with nitrogen

nucleophiles (they are bases).

No SN2 substitution. In highdielectric ionizing solvents

SN1 and E1 products may be

formed.


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18 Nagham Mahmood Aljamali

Impact Factor (JCC): 3.5367 Index Copernicus Value (ICV): 3.0

Table 1: Contd.,

AllylH2C=CHCH2–

Rapid SN2 substitution for

1º and 2º-halides. For 3º-

halides a very slow SN2substitution or, if the

nucleophile is moderately

basic, E2 elimination. Inhigh dielectric ionizing



acetonitrile, SN1 and E1

products may be observed.


1º halides. E2 eliminationwill compete with

substitution in 2º-halides,

and dominate in the case of3º-halides. In high

dielectric ionizing solvents

SN1 and E1 products may

be formed.

Nitrogen and sulfur

nucleophiles will give SN2

substitution in the case of 1º

and 2º-halides. 3º-halides will

probably give E2 elimination

with nitrogen nucleophiles(they are bases). In high

dielectric ionizing solventsSN1 and E1 products may be

formed. Water hydrolysis will

be favorable for 2º & 3º-halides.

Benzyl

C6H5CH2–


1º and 2º-halides. For 3º-

halides a very slow SN2

substitution or, if the

nucleophile is moderately

basic, E2 elimination. Inhigh dielectric ionizing



acetonitrile, SN1 and E1products may be observed.

Rapid SN2 substitution for1º halides (note there are no

β hydrogens). E2

elimination will competewith substitution in 2º-

halides, and dominate in

the case of 3º-halides. Inhigh dielectric ionizing

solvents SN1 and E1products may be formed.

Nitrogen and sulfur

nucleophiles will give SN2substitution in the case of 1º

and 2º-halides. 3º-halides will

probably give E2 eliminationwith nitrogen nucleophiles

(they are bases). In high

dielectric ionizing solventsSN1 and E1 products may be

formed. Water hydrolysis willbe favorable for 2º & 3º-

halides.

In General

Figure 27

Figure 28

Substitution versus Elimination Guidelines

• The strength of a base or nucleophile will dictate the order of a reaction. (Strong bases/nucleophiles will react

more quickly and create 2nd order kinetics).


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• Primary halides usually undergo SN2 with good nucleophiles. Also watch for rearrangements to more stable

cations if ionization is possible.

• Tertiary halides usually do not undergo SN2 reactions. More likely to undergo E2 with a good base, or E1 and

SN1 otherwise.

• Secondary halides can react in all ways (hard to predict).

• High temperatures favor elimination.

• The nucleophile/base will usually favor one or the other type of reaction. (t-butoxide favors elimination, bromide

and iodide favor substitution).

Figure 29

Identification Test of Halides

The halogenoalkane is warmed with some sodium hydroxide solution in a mixture of ethanol and water.

Everything will dissolve in this mixture and so you can get a good reaction. The halogen atom is displaced as a halide ion:

R−X + OH−→R−OH + X−

With X is any haligen atom.

There is no need to make this reaction go to completion. The silver nitrate test is sensitive enough to detect fairly

small concentrations of halide ions. The mixture is acidified by adding dilute nitric acid. This prevents unreacted hydroxide

ions reacting with the silver ions. Then silver nitrate solution is added. Various precipitates may be formed from the

reaction between the silver and halide ions:

Table 2

Ion

PresentObservation

Cl

-

white precipitateBr- very pale cream precipitate

I- very pale yellow precipitate

Comparing the Reaction Rates (Type of Halogen)

You would have to keep the type of halogenoalkane (primary, secondary or tertiary) constant, but vary the

halogen. You might, for example, compare the times taken to produce a precipitate from this series of primary

halogenoalkanes:


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20 Nagham Mahmood Aljamali

Impact Factor (JCC): 3.5367 Index Copernicus Value (ICV): 3.0

Figure 30

Obviously, the time taken for a precipitate of silver halide to appear will depend on how much of everything you

use and the temperature at which the reaction is carried out. But the pattern of results is always the same. For example:

• A primary iodo compound produces a precipitate quite quickly.

• A primary bromo compound takes longer to give a precipitate.

• A primary chloro compound probably won't give any precipitate until well after you have lost interest in the

whole thing!

The order of reactivity reflects the strengths of the carbon-halogen bonds. The carbon-iodine bond is the weakest

and the carbon-chlorine the strongest of the three bonds. In order for a halide ion to be produced, the carbon-halogen bond

has to be broken. The weaker the bond, the easier that is.

If you have looked at the mechanisms for these reactions, you will know that a lone pair on a water molecule

attacks the slightly positive carbon atom attached to the halogen. It is slightly positive because most of the halogens are

more electronegative than carbon, and so pull electrons away from the carbon.

It is tempting to think that the reaction will be faster if the electronegativity difference is greater. The slight

positive charge on the carbon will be larger if it is attached to a chlorine atom than to an iodine atom.

That means that there will be more attraction between a lone pair on the water and a carbon atom attached to a

chlorine atom than if it was attached to an iodine atom. The electro negativity difference between carbon and iodine is

negligible.

However, the fastest reaction is with an iodoalkane. In these reactions, bond strength is the main factor deciding

the relative rates of reaction.

Comparing the Reaction Rates of( Primary, Secondary and Tertiary Alkyl Halide)

You would need to keep the halogen atom constant. It is common to use bromides because they have moderate

reaction rates. You could, for example, compare the reactivity of these compounds:

Figure 31

Again, the actual times taken will vary with reaction conditions, but the pattern will always be the same. For

example:


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• The tertiary halide produces a precipitate almost instantly.

• The secondary halide gives a slight precipitate after a few seconds. The precipitate thickens up with time.

• The primary halide may take considerably longer to produce a precipitate.

It is more difficult to explain the reason for this, because it needs a fairly intimate knowledge of the mechanisms

involved in the reactions. It reflects the change in the way that the halide ion is produced as you go from primary to

secondary to tertiary halogenoalkanes.

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S . George ., ''Organic Chemistry" Mosby-Year Book . 1995, Chp.14, p. 589-649 (1995).

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L.F. Fieser and K.L. Eilliamson, ''Organic Experiment" 5th Ed ., DC . Heath and company Toronto, Canada, p.

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Y. Liu, Y. Xu, S. H. Jung, J. Chae, Synlett, 2012, 2663-2666.

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Louis D. Quin and Tohn A. Tyrell, ''Fundamentals of Heterocyclic Chemistry'' 9th Ed.,Wiley, New York, (2010)

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2. Chemical - IJCPT- Survey on Alkyl Halide Compounds