Script
Basics
Curly arrow mechanisms are used a lot in chemistry to show the mechanism of a reaction,
but they can look scary and complicated. How do you know where to put the arrows and
dots? Once you know the basics, curly arrow mechanisms are quite easy.
Curly arrows show the transfer of electrons. Electrons move from electron rich areas to
electron poor areas. A single headed arrow shows the movement of only one electron,
and is needed to describe free radical reactions. A double headed arrow shows the
movement of an electron pair, such as from a lone pair or a bond. We will mostly use the
double headed curly arrow.
The tail of the arrow begins at the original location of the electrons, which could be a
lone pair, a negative charge on a nucleophile, a base, or the bond between two atoms.
The head of the curly arrow always points to where the electrons are going. For example,
when a carbonyl group is protonated, the electron pair on the oxygen grabs a positively
charged hydrogen, a proton. This is described mechanistically by drawing a doubleheaded curly arrow from the oxygen lone pair to the proton. In the product the electron
pair now forms a bond between these two atoms. Protonations are not only very fast,
they are also reversible. In the reverse reaction, the bond between the oxygen and the
hydrogen is broken, the electrons move from the bond back to the oxygen, leaving a
proton behind. Again, this is illustrated by the double headed arrow moving from the
bond back to the oxygen. Remember also, the charges on either side of the reaction
should balance.
Curly arrows are only used to show the movement of electrons, so the H+ does not attack
the oxygen, the electrons on the oxygen attacks the proton H+. The H+ is an electrophile,
as it is attracted to a negative centre, whereas the oxygen is a nucleophile, as it is
attracted to a positive centre.
SN2
The first reaction we will look at is the SN2 reaction; a nucleophilic substitution that
follows second order kinetics, meaning the rate of the reaction relies on 2 molecules.
This is a substitution reaction that is typical for many primary and secondary alkyl
halides and related compounds with a good leaving group. The nucleophile always
attacks from the back, on the opposite side from the leaving group, expelling the leaving
group. In this reaction, the nucleophile, a hydroxide ion, attacks the electrophilic carbon
centre, on the opposite side from the bromide leaving group. A new bond is formed with
the carbon at the same time as the bond to the bromide ion breaks. This forms a
transition state, where the carbon is partially bonded to both groups at the same time.
The leaving group breaks away, and we get the product, an alcohol. SN2 reactions always
go with inversion of stereochemistry, which will be important if the starting material is
chiral.
SN1
Another substitution reaction is the SN1 reaction, where the 1 indicates first order
kinetics. The rate of this substitution depends only on one reaction participant. It occurs
under acidic conditions and is incompatible with strong bases, such as hydroxide or
alkoxide. The SN1 reaction proceeds through a carbocation intermediate. Tertiary
halides favour SN1 substitution. The presence of three substituents blocks direct attack of
the nucleophile from the back, and the substituents help to stabilise the intermediate
carbocation. In this example, the bromide ion leaving group breaks away first from the
rest of the molecule. This process is slow and reversible, and leaves a positively charged
carbocation intermediate. The nucleophile then attacks the carbocation, and loss of a
proton results in the neutral product. As the intermediate is a trigonal planar carbocation,
the nucleophile can attack from either face, leading to a racemic product.
E2
We will now consider elimination reactions. The first of these is the E2 reaction, which
is a second order reaction. An E2 elimination requires that the leaving group, the 2
carbons forming the C=C double bond and the hydrogen are all in the same plane. We
call this arrangement “antiperiplanar” and it is a key feature of the E2 mechanism. The
base, ethoxide in this case, removes the proton β to the leaving group. The electron pair
of the C-H bond moves to form the carbon-carbon π-bond, and the carbon-chlorine bond
is broken, with the electrons moving with the chlorine. All of this happens at the same
time and produces the alkene product, ethanol and a chloride ion.
Depending on the arrangement of the groups on the carbons before elimination, either a
cis or a trans product can sometimes be formed.
E1
Elimination can also occur by an E1 mechanism. Like an SN1 substitution, the E1
elimination is a two-step process which is favoured by tertiary compounds and involves a
carbocation intermediate. Both SN1 and E1 occur under acid conditions. As with the SN1
mechanism, the chlorine leaving group separates first, and a carbocation is formed. This
step is slow and reversible. In the absence of a good nucleophile, the carbocation then
loses a proton to form the C=C double bond of the alkene product.
Key features of substitution and elimination reactions
SN1 and SN2 are both substitution reactions. A good leaving group, such as bromine or
chlorine, is substituted for the attacking nucleophile. E1 and E2 are both elimination
reactions, where groups are removed from the compound, forming alkene products. SN1
and E1 are similar in mechanism, as both proceed via a carbocation intermediate, and
require an acid catalysis. Elimination by E1 is often a side reaction during an SN1
substitution and is particularly prone to happen at higher temperature. SN2 and E2 also
have similarities in that they pass through a transition state, and no intermediate is
involved. The E2 reaction will occur under basic conditions.
Addition on C=C
Let us now look at addition reactions. The carbon-carbon double bond of an alkene is
electron rich, so most reactions with it involve electrophiles. For example, hydrogen
halides are strong acids which can protonate an alkene, such as 2-methyl-2-propene.
Protonation leads to a carbocation intermediate. This is then attacked by the bromide
counter-anion to give the addition product. The addition of HBr to the alkene follows
Markownikoff’s rule and the bromine ends up on the more substituted former alkene
carbon. The reason for this is that protonation occurs first and will always give the more
substituted and thus more stable carbocation intermediate.
Addition on C=O
Addition can also occur on the C=O double bond. The carbonyl group is polarised, with
the electronegative oxygen bearing a delta negative charge and the carbonyl carbon a
delta positive charge. Reactions of the carbonyl group are dominated on the addition of
the nucleophile to the electron deficient carbon. The mechanism, and rate of reaction,
varies with the nucleophile. A good nucleophile, such as a Grignard reagent, will attack
the carbonyl carbon directly. The resulting alkoxide is then protonated during an acidic
work up. The reaction of a ketone or aldehyde with a poor nucleophile doesn’t work
unless it is catalysed by an acid. Protonation of the carbonyl group is essential before a
bad nucleophile can attack. A typical example includes the formation of an oxime.
In this example, the carbonyl group is protonated. This makes the carbonyl carbon much
more delta positive. The nucleophile, hydroxylamine, now can attack the electron
deficient carbon. The nitrogen then loses a proton, while the OH picks up another proton
and is transformed in a good leaving group. The lone pair of the nitrogen comes in to
form a double at the same time when water is eliminated. Loss of a proton finally gives
the oxime product.
Carboxylic acids and their derivatives (esters, amides, and acid chlorides) differ from
ketones and aldehydes in that they have a leaving group attached to the carbonyl group.
So, attack of a nucleophile at an ester gives initially a tetrahedral intermediate, but the
reaction doesn’t stop there. The tetrahedral intermediate then loses the leaving group and
reforms the C=O double bond. This is saponification of an ester, and the overall reaction
is a “substitution” at an acyl carbon.
Electrophilic Aromatic Substitution
The final mechanism we will look at is that of an electrophilic aromatic substitution.
Unlike alkenes which prefer addition reactions, the reaction of benzene with an
electrophile involves the replacement, substitution, of a group, in most cases just a
hydrogen atom, to give a substituted benzene. Many aromatic compounds are electron
rich in nature, and prefer substitution by an electrophile. The electrophile is generally an
electron deficient group, such as a cation; it could even be a proton although this won’t
be very productive. A typical example of an electrophilic aromatic substitution is the
Friedel-Crafts alkylation, where an alkyl halide is combined with anhydrous AlCl3 in situ.
Aluminium trichloride is a Lewis acid which triggers the dissociation of the carbonchlorine bond, and the result is an alkyl cation. In truth, this is a rather simplistic view
since primary alkyl cations in particular are so unfavourable that the carbon-chlorine
bond is only weakened rather than broken, but it acts as a separate cation.
Benzene now reacts with the alkyl cation. We indicate this by drawing a curly arrow
from the benzene to the carbocation. Although the aromaticity of the benzene ring is
destroyed, the intermediate carbocation (called the Wheland intermediate) is stabilised by
resonance and the positive charge is shared around the ring. In the final step, the
electrons from the carbon hydrogen bond move into the ring and regenerate the aromatic
ring. At the same time, the hydrogen atom and the positive charge are lost in form of a
proton. The overall result is that the hydrogen has been substituted by an alkyl group.
There are many other types of aromatic substitution. There is the related Friedel-Crafts
acylation which uses an acyl halide and involves a resonance-stabilised acyl cation as the
electrophile.
Another common example is halogenation where a halogen, such as chlorine, when
combined with catalytic amounts of iron(III) chloride becomes polarised, so that the
aromatic ring reacts with what is almost like a Cl+.
Nitrations involve an NO2+ electrophile, the nitronium ion, which is generated in situ
from a mixture of concentrated nitric acid and concentrated sulfuric acid. This is an
important reaction as these can be reduced to aminobenzenes. These are very important
in the pharmaceutical industry, in the production of paracetamol.