Unit and Compound Mechanistic Steps
process can be deconstructed into sequences of substitution- transfer- abstraction-
displacement or STAD steps, as suggested previously,
however it remains convenient to classify mechanisms in terms of complexation,
elimination, rearrangement, etc.
Rigorous deconstruction to
the STAD level is not particularly useful when trying to understand reaction
mechanism science. It is better to consider mechanisms in terms of concerted
unit mechanisms, and to construct multistep compound mechanisms
from sequences of these concerted unit mechanisms. We will examine:
It is not that aim of this
page say everything-that-can-be-said about reaction mechanisms,
that would be impossible. Instead, the emphasis will be on the various
types of concerted and stepwise atom-to-atom mappings which are available,
- Concerted vs. Stepwise
- 1,2-Addition vs, 1,4-addition,
in preference to looking at the various subtypes of 1,2-addition.
- Single-step 1,2-addition
vs. chain 1,2-addition.
- Fragmentation vs.
complexation, and elimination vs. addition.
Little is said on this page
about nucleophilic substitution or radical chain addition,
etc., although it will sometimes be necessary to illustrate a general
point with a specific instance.
The complexation of Lewis acids
and Lewis bases and radical coupling has been discussed at length elsewhere
in this web book, here
and here, and nothing will be
added here about the types of complexation. In this section we
are looking at X + Y → X-Y, pure and simple.
The first thing to say is that
complexation is a fundamental, concerted, single-step, unit mechanistic
by definition involves bond formation, and bond formation
is an exothermic process. The result that a complexation reaction will
have a negative ΔH (enthalpy) value.
This must be the case because
the bonded state complex, X-Y, will always have a lower energy than
the free species X + Y, or the bonded state would not form. The law
of conservation of energy tells us that this bonding energy must be
released in some way, usually as heat.
But, X + Y involves two species,
while X-Y involves only one. The result is that X + Y has more entropy
in other words the system is more dispersed than the complexed
The Gibbs free energy relationship,
ΔG = ΔH
T DS, for this system tells us that complexation
vs. decomplexation is a subtle balance between two components:
- Enthalpy, or heat
- Entropy, the tendency
of the system to disperse.
- The crucial point is that the entropy component is multiplied by the thermodynamic temperature,
so as the temperature increases the entropy component becomes more important
and fragmentation dominates. Conversely, at low temperatures complexation
However, there is a third factor
which is not explicitly dealt with by the Gibbs equation: activation energy.
At room temperature, X and Y may coexist together indefinitely, while
at 120°C the reaction to X-Y may proceed.
So, the X + Y →
X-Y reaction may require moderate heating to overcome the activation
energy of the reaction, but if the XY complex is heated too strongly
it will invariably fragment to X + Y.
(heat of reaction) of the X + Y →
X-Y reaction must be removed in some way, or X-Y will fragment back to
X + Y. This is not a problem in the liquid phase where the heat or formation
can be conducted away by the solvent, but this is not the case
in the gas phase the newly formed XY, or rather [X-Y]*, will be
so vibrationally excited, or "hot", that it will fragment. The
newly formed [X-Y]* must transfer this excess energy away to another species
or the walls of the vessel. For this reason gas phase complexation reactions
are often shown with a third species, m:
X + Y + m → XY + m*
In the reaction, m
is heated to the species m* which carries away the excess kinetic
and thermal energy, here.
Although often shown as a three-centre process, the reaction is more
likely to be stepwise, it all depends of the timing:
X + Y → [XY]*
[XY]* + m
→ X-Y + m*
Indeed, complexation only ever
involves two species coming together single step (concerted) because
the three centre complexation process:
X + Y + Z → X-Y-Z
is statistically unlikely.
When an X + Y
←→ X-Y reaction is at thermal equilibrium, fragmentation is the
reverse of complexation. But this condition does not always hold. Fragmentation
need not be the reverse of complexation because a chemical compound can
fragment into any number of pieces.
Trinitrotoluene, TNT, C7H5N3O6,
has a molecular weight of 227.13. On heating, the TNT molecule
rapidly disassembles into a zoo of small, hot gas molecules: CO2,
N2, NO2, H2O,
The explosive fragmentation
of TNT to thermodynamically stable molecules like N2
and CO2 is favourable on both enthalpy and entropy
ligand exchange reaction can either proceed via a concerted STAD mechanism
or by a sequence of fragmentation-followed-by-complexation steps.
Consider a tetrahedral (sp3)
carbon centre with four different ligands, L1, L2,
L3 and X, arranged so the carbon centre is
chiral and optically active (ie., a single enantiomer).
A reaction occurs where X
is replaced by Y. This can occur in two general ways:
Y may complex with
the carbon centre to give a hypervalent three-centre transition state
that immediately collapses back to a tetrahedral configuration with
the ejection of X. The rate of this concerted bimolecular reaction
is dependent upon the concentrations of both [L3CX]
and [Y] and so is classed as a Second Order substitution. The
backside attack mechanism means that the carbon centre "inverts"
to give a Y substituted product of opposite configuration and
the carbon centre remains as a single, optically active enantiomer:
Note that the
phrase "opposite configuration" is sensitive to the way
in which configuration is defined, and there are three different
systems: D/L, +/ or R/S. (The forth d/l system is the same as
the +/ system.)
Alternatively, the substitution
reaction may proceed in a stepwise manner with X leaving as a
first step to give a hypovalent three-centre transition state, L3C,
which subsequently complexes with Y. The rate of the reaction
is dependent only upon the rate of fragmentation of [L3CX]
and so is classed as a unimolecular or First Order process. The three
centre intermediate can be attacked by Y from "either side"
and this leads to the scrambling of the chiral centre to give a non-optically
active, racemic, product mixture.
It is usually the case that:
are stereospecific and chirality retained.
tend to racemise chiral centres which removes optical activity.
Ligand substitution reactions
are also seen in inorganic octahedral complexes. Again, there are two
Ia, which involves a hypervalent seven centred
Id, which has a hypovalent five centred intermediate.
However, the difference between
the Ia and the Id mechanisms
is not nearly as clear cut as between first and second order substitution
at a carbon centre, and there are many intermediate cases. Inorganic
ligand substitution mechanisms are discussed in considerable detail,
Ligand interchange also occurs
at square planar complexes:
Square planar complexes are
commonly associated with Ni, Pd, Pt and other centres, here.
Ligands substitute in a stepwise
or one-at-a-time manner, and the intermediate compounds can be isolated
and purified. It has been found that the second substituting ligand has
a choice and can substitute in two ways so that the disubstituted square
planar complex can have either a cis or a trans configuration.
Furthermore, it has also been
found that when going from MX4 → MY4
the disubstituted intermediate may be trans, but when going from
MY4 the disubstituted intermediate may be cis.
The "trans effect"
seen with chloride and ammonia ligands displacing each other at a platinum(II)
centre. And this chemistry is not simply of dry academic interest because
the cis platinum complex, cis diamminedichloroplatinum (or
is an important and widely
used anticancer drug known as cisplatin, search here.
When a chemical
species "squeezes-in" between two existing species, the reaction
can be classed as an insertion. However, true, concerted reactions are
comparatively rare and most examples are seen in organometallic chemistry
and with diradicals.
If the insertion proceeds
as a single step, then the insertion process can be regarded as a special
case of complexation, and the temperature dependence arguments associated
with complexation apply, here.
Insertion can also
be regarded as 1,1-addition.
Insertion can also
be regarded as a redox process because it is usual for the oxidation
and/or coordination number of the inserted species to increase.
Insertion can occur
via a sequence of mechanistic steps with insertion only as the overall
The direct insertion of a species
into a chemical bond is common in organometallic chemistry where metals
frequently insert into carbon halogen bonds. The process is called metallation.
Magnesium metal, Mg, inserts
into the carbon iodine bond of methyl iodide, H3C-I,
to give the well-known Grignard reagent, methyl magnesium iodide. This
process can also be classed as an oxidative addition because the oxidation
state of the magnesium increases from 0 to +2. The reaction is thought
to involve single electron transfer (SET).
In recent years there has
much interest in organopalladium chemistry. The first step of the synthetically
reaction involves a palladium(II) salt inserting into an aromatic
halogen bond. This insertion (which has been simplified in the diagram
below) is also classed as an oxidative addition because the palladium
is oxidised from +2 to +4.
Consider the reaction of phosphorus
trichloride, PCl3, with chlorine, Cl2,
to give phosphorus pentachloride, PCl5. In this
reaction, which is often used to illustrate chemical equilibrium, the
PCl3 [can be considered to] insert into the Cl-Cl
bond, with the oxidation number of the phosphorus increasing from +3 to
Carbenes are very reactive
diradicals species, and it has been suggested that the parent carbene
species, methylene or CH2, is the most reactive
of all organic moieties. Methylene which is divalent can
insert into alkane CH and CC bonds to give a tetravalent species.
However, these reactions are very unselective and of little synthetic
is less reactive than methylene. It is generated from chloroform (trichloromethane,
CHCl3) and strong base which initiates the 1,1-elimination
+ NaOH > CCl2 + NaCl + H2O
Dichlorocarbene is able to
react with the heterocycle pyrrole to give 3-chloropyridine, admittedly
in low yield:
This Reimer-Tiemann reaction
is, overall, an insertion of carbon into the aromatic ring system
which expands from a 5 to a 6 membered system. However, the reaction
proceeds by quite a number of discrete steps.
Another example of multistep
insertion is the oxidation of an "allylic" carbon to a hydroperoxide,
This oxidation process is
very important in the food industry where it is involved in the degradation
of unsaturated fats and oils.
Pericyclic reactions have a
cyclic transition state which allows for the concerted rearrangement of
the electrons so that sigma and π-bonds
to simultaneously break and form. Four subclasses of pericyclic reaction
can be recognised and we will use this system:
Group Transfer Reactions
Pericyclic reactions are discussed
in their own section, here.
The classic metathesis
reaction is also called a double displacement reaction. This type of metathesis occurs when aqueous solutions of two soluble salts are added
together and an insoluble precipitate appears:
When aqueous solutions of
lead(II) nitrate, Pb(NO3)2,
and potassium iodide, KI, are mixed, a precipitate of lead(II) iodide,
PbI2, appears and the potassium nitrate, KNO3,
remains in solution. The ions "swap". Likewise, mixing aqueous
solutions of silver nitrate, AgNO3, and sodium
chloride, NaCl, gives a precipitate of silver chloride, AgCl, and sodium
nitrate, KNO3, remains in solution:
The driving force for these
reactions is the formation of a low solubility precipitate. If there
where to be no precipitate the four species (two cations and two anions)
would simply remain in solution.
reactions can be used to identify metal ions in solution, and extensive
analytical methodologies have been developed using this approach, see
Qualitative Inorganic Analysis by Vogel). However, these wet
chemistry techniques have fallen out of use because instrumental methods
of analysis such as atomic absorption spectroscopy and ICP-MS, are:
easier to perform, faster, more accurate, more precise, and they are
far, far more sensitive.
Substituted alkenes (olefins)
undergo olefin metathesis, a reaction catalysed by transition metals
(often Mo, W or Re) in the presence of a trialkyl aluminium, AlR3,
alkylating agent. During the metathesis the alkene ligands are exchanged
between the alkenes. The reaction process is most clearly visualised when
a cyclic alkene undergoes olefin metathesis with a linear alkene. The
product is a linear diene, but there are many by-products.
Note that in the diagram
above, the alkene double bonds are shown cis, but this is only
for clarity. Mixtures are cis and trans isomers are formed.
It is tempting to postulate
a cyclic four membered "pericyclic type" transition state
associated with the transition metal centre... but kinetic measurements
and examination of product ratios indicates that this is not the case.
It is more likely that the reaction is stepwise, and involves metal=carbene
Yves Chauvin, Robert H. Grubbs, and Richard R. Schrock shared the 2005 Nobel Prize in Chemistry for "the development of the metathesis method in organic synthesis". Wikipedia
usually involve two species complexing to the two ends of a π-system,
with the π-system
correspondingly reducing in length. Typical reactions of this type would
be the addition of bromine, Br2, to a 1,4-diene:
There are two products, one
formed by 1,2-addition and the other formed by 1,4-addition.
In each case the π-systems
reduces from a 4 π-electron
system to a 2 π-electron
The numbers "1,2"
and "1,4" refer to the π-system
and should not be confused with the numbering system used to name the
Using the addition reaction
nomenclature system, we can consider the reaction of carbon monoxide,
CO, with chlorine to give phosgene to be a 1,1-addition:
However, this reaction can
also be considered to be an insertion of carbon monoxide into the Cl-Cl
bond, or as a special case of complexation.
Addition reactions are net
bonding processes and are thermodynamically similar to complexation, here.
Play with the Addition Reaction Synthlet.
Cyclohexene: A Model System
Cyclohexene is a wonderful
model system to use for the study the subtleties of addition. At the simplest
level, a species X2 adds to cyclohexene to give
a 1,2-disubstituted cyclohexene.
There are several examples:
Cl2, Br2, I2
and H2 all add to cyclohexene in this manner.
Chlorine adds to give 1,2-dichlorocyclohexane. Hydrogen adds
with the help of a Pt catalyst to give cyclohexane.
It is plausible for X2
to add to cyclohexene in two ways: syn and anti.
syn-Addition is deemed
to occur when the two X atoms add to the same face of the cyclohexene
ring, the result is a cis-1,2-disubstituted cyclohexane.
anti-Addition is deemed
to occur when the two X atoms add to opposite sides of the cyclohexene
to give a trans-1,2-disubstituted cyclohexane.
There is an important steric
constraint if the two X functions to add in a syn manner: they
must be connected in some way. Either the two X functions must be part
of the same molecule, in which case the reaction is a cycloaddition,
or they must be served in some syn manner. An example
would be catalytic hydrogenation where hydrogen is first adsorbed onto
a metal surface, from where it is received by the alkene in a syn
Conversely, to form the anti-addition
product, the two X functions cannot be connected and the reaction must
proceed in some kind of stepwise manner:
Stereochemical control of
stepwise anti-addition can be maintained by first applying concerted
syn cycloaddition, and then ring opening via concerted substitution:
Consider a polar species, X-Y,
adding to 1-methyl cyclohexene, where X is electronegative and Y is electropositive.
Examples of polar-species-which-add would include: H-Cl, H-Br or H-OH
(H2O). There are two possible modes of addition:
- Markovnikov addition
where the electronegative atom, X, adds to the more substituted carbon
addition where the electronegative atom, X, adds to the less substituted
The syn and anti
type additions can be combined with the Markovnikov and anti-Markovnikov
type additions to give a number of possible products. Consider the 1-methylcyclohexene
with an additional bulky group, R, to make the molecule chiral (which
actually makes the analysis easier.) Consider the addition of water. There
are six possible H2O addition products for this
Using a variety of reagents
and techniques, it is possible make all six of the alcohols stereospecifically.
But they cannot not all be made in a single preparative step.
1,2-Addition reactions can
chain propagate to produce polymers:
A growing polymer chain with
a reactive centre, *, adds to an alkene, or a functionilised alkene,
where FG can be Cl, CN, C6H5,
etc., to produce a chain two carbon atoms longer with a new reactive
centre which is able to partake in another addition... and so on...
the nature of the FG and the initiator, 1,2-chain addition can be cationic,
radical or anionic in nature, and examples of each type are known:
Concerted, single step cycloaddition
reactions are pericyclic processes (see above).
Addition proceeds via single
or sequential complexation, and is an exothermic process:
Like complexation, an elevated
temperature may be needed to overcome the reaction's activation energy,
but very high temperatures will cause elimination.
It is tempting
to think of elimination as the opposite or reverse of addition because
1,2-addition and 1,2-elimination reactions can be complementary. For example,
ethene, CH2=CH2, reacts with
hydrogen chloride, HCl, to give chloroethane... and chloroethane is able
to lose HCl to give ethene:
But the ionic
mechanisms are entirely different:
The forward reactions proceeds
by two discrete steps: protonation of the electron rich π-system
to give the carbenium ion intermediate which is subsequently complexed
by the chloride ion:
The reverse reaction proceeds
rather easily through base catalysed beta-elimination. This concerted
reaction involves a base abstracting a beta-proton. In one concerted
step the proton is removed, the π-bond
is formed and the chloride ion is ejected:
The concerted beta-elimination
mechanistic process cannot happen in reverse (in a homogeneous environment),
because the proton, chloride ion and alkene would have to find themselves
precisely aligned in space, statistically a very unlikely scenario.
Elimination is a type of fragmentation
and by whatever mechanism it occurs (beta-elimination, retrocycloaddition
or stepwise elimination) is encouraged on thermodynamic grounds by increasing
temperature and decreasing pressure:
The products of elimination
have more entropy.
is deemed to have occurred when a function, R, moves along a chain of
Schematically, the [1,2] rearrangement
involves R moving to an adjacent atom:
There quite a number of named
[1,2] rearrangements which occur to specific organic functional groups
under specific conditions. Some of these name reactions proceed in a concerted
manner via cyclic intermediates and some may be stepwise:
Overall, these can be represented
occur when a function, R, moves along a chain of j atoms.
While there is
great variety amongst [1,2] shift rearrangements, the longer migrations
invariably proceed via a concerted pericyclic mechanism, here,
however, the charges and bonds can be accounted for using curly arrows:
There are some interesting
reactivity patterns with [1,j] rearrangements:
- [1,2], [1,4] and [1,6]
rearrangement requires a cationic or anionic centre.
- [1,3], [1,5] and [1,7]
rearrangements can occur with neutral systems. (Note
that with these neutral rearrangement systems, the curly arrows can
be constructed in equivalent clockwise or anticlockwise directions,
but only one is shown.)
- These pericyclic reactions
can be activated by heat or UV light. The Woodward-Hoffmann rules can
be used to predict the stereochemical consequences, see here
It is interesting to ask why
a rearrangement reaction should proceed at all, because the way the reactions
diagrams are drawn in the diagram above, there is no apparent energy difference
between the left and side and the right hand side of the reaction equations,
and so no driving force.
Consider the reaction of butane
with aluminium chloride plus a catalytic quantity of 1-chlorobutane at
150°C. These conditions give an equilibrium mixture consisting of
20% butane (n-butane) and 80% methylpropane (iso-butane) .
The reaction, a Wagner-Meewein
rearrangement. It proceeds by the aluminium chloride abstracting a chlorine
anion from the RCl to generate a carbenium ion. The carbenium ion abstracts
a hydride from butane to produce a [C4H9]+
carbenium ion. This carbenium ion can [1,2] shift a methyl function
to give (after hydride abstraction) the branched isobutane:
This apparently simple example
of a [1,2] shift is actually quite involved because the product ratio
is the balance of two competing stability issues:
- Branched alkanes,
with tertiary and quaternary carbon centres, are thermodynamically
more stable than linear alkanes. Butane has an energetic tendency
to isomerise to methylpropane.
- Secondary carbenium
ions, R2HC+, are more stable than primary carbenium ions,
> R2HC+ >
An R moiety will [1,2]
In isolation the equilibrium
position of the [1,2] rearrangement lies to the side of linear butane
2° carbenium ion, but the equilibrium is pulled over to methylpropane
due to the greater thermodynamic stability associated with the more
substituted carbon centre.
Note. This reaction tells
us that methyl groups must have a much greater tendency to migrate than
hydrogen under carbenium ion conditions. If this were not so the the
most stable carbenium ion, the tertiary butyl cation, (CH3)3C+,
would form leading to 100% methylpropane (isobutane).
The thermodynamic stability
of branched alkanes over linear alkanes is exploited in the petrochemical
industry where the process of hydrocracking
is used to convert longer, linear alkanes into shorter branched alkanes.
A wide range of materials can be produced and the process can be optimised
for gasoline or kerosene production. Hydrogen, shape selective zeolite
catalysts, 340-450°C cracking temperatures and 80-200 bar pressures are
There is an amusing synthetic chemistry story that illustrates how the subtle kinetic and thermodynamic
effects associated with rearrangement reactions can be exploited.
Synthetic chemists enjoy
making target molecules, usually natural products or
molecules with interesting symmetry. One such target was adamantane,
C10H16, a beautifully
symmetric hydrocarbon which is the hydrocarbon derivative of a single
unit cell of diamond:
synthesis of adamantane was successfully devised, implemented and
the results published. Success!
a few years later it was discovered that if the dimer of cyclopentadiene
is hydrogenated and treated with AlCl3 + RCl,
a series of Wagner-Meewein cationic [1,2] shifts occur and adamantane
is produced in 15% yield:
It was subsequently demonstrated
that any C10H16
alkane will rearrange to a 15% equilibrium mixture of adamantane under
Rearrangements can occur in
which two chains "move with respect to each other"... although
this is easier to explain and visualise with graphics than words:
In these rearrangements a "two"
unit moves with respect to a "three" unit hence [2,3], and a
"three" unit moves with respect to a "three" unit,
[3,4], [3,5], [4,5], [5,5],
[9,9] etc. rearrangements are all known. All of these should be considered
as sigmatropic processes, which are discussed here.
Many, many many
reactions only occur to specific functional groups under specific conditions
and they usually involve quite a number of discrete mechanistic steps.
It is common to
refer to such reactions by a name... often the name of the chemist who
first observed or exploited the reaction.
There are several
web sites which deal with organic name reactions:
Chem's Name Reaction List
Reactions in Organic Chemistry
Reactions in Organic Chemistry
|The STAD Mechanistic Step
The Mechanism Matrix
© Mark R. Leach 1999-
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