Whitehead’s Process Model and the Hughes-Ingold Model in Organic
Chemistry
Michael Akeroyd
Bradford College, BD7 1AY, UK
m.akeroyd@bradfordcollege.ac.uk
In the Lowell Lectures, 1925 (subsequently published in ‘Science in the
Modern World’, 1926, reprinted CUP, 1953), Whitehead attacked
deterministic models in physical science on p. 99 and pp. 133-4.
On p. 99 he wrote: ‘In this [my] theory, the molecules may blindly run
in accordance with the general laws, but the molecules differ in their
intrinsic characters according to the general organic plans of the
situations in which they find themselves.’
One of the problems facing physical organic chemists from 1925-1952 was
that, in solvolytic reactions involving alkyl halides, the ‘reactive’
hydroxide ion sometimes acted as a stronger attacking species than the
water molecule and sometimes as a weaker species in apparently
analogous circumstances. The then current deterministic model could
offer no solution to this problem. A solution was offered from two
chemists, E. D. Hughes and C. K. Ingold, utilizing a process
methodology in line with Whiteheadean precepts. The role of the
supposedly inert solvent (an 80:20 ethanol:water mixture) was far more
subtle than previously supposed and offered a variety of situational
‘organic plans’ mentioned above.
Science in the Modern World
A N Whitehead 1926, Cambridge University Press 1953
‘I would term the doctrine of these lectures organic mechanism.
In this theory, the molecules may blindly run in accordance
with general laws, but the molecules differ in their intrinsic
characters according to the general organic plans of the
situations in which they find themselves. (Page 99)
‘The laws of physics are the laws declaring how the entities
mutually react among themselves. For physics the laws are
arbitrary, because science has abstracted from what the
entities are in themselves. We have seen that the fact of what
the entities are in themselves is liable to modification in their
environments. Accordingly, the assumption that no
modification of these laws is to be looked for in environments,
which have any striking differences from the environments for
which the laws have been observed to hold, is very unsafe.The
physical entities may be modified in very essential ways, so far
as these laws are concerned.’ (pp. 133-134)
Mechanism of reactions in Organic Chemistry
From 1840-1930 over 1 million organic reactions had been
catalogued. The accepted theory was that all reactions
proceeded by collision theory.
H3CH2C*X
HO*Na
H3CH2C*O*H
NaX
H3CH2C*X
HO*H
H3CH2C*O*H
HX
An important class of organic reactions was the solvolyses of
alkyl halides (haloalkanes). However in 1927 the UK organic
chemist Ward noted something odd:
When primary (CH3CH2X) halides and secondary (CH3)2CHX
halides reacted in ethanol/water mixtures, addition of small
amounts of NaOH increased the reaction rate (as one would
expect since OH- ion is much more reactive), but when tertiary
(CH3)3CX halides reacted, their much more rapid reaction rate
was totally unaffected by the addition of NaOH.
It seems plausible to suggest that the presence of three bulky
alkyl groups round the starred carbon atom sterically hinders
the approach of the reactive hydroxide ion from the back to
form an activated complex but why then does the less reactive
and more bulky water molecule prove a much more successful
nucleophile?
In 1933 the UK chemists Hughes and Ingold (and in 1938 the
US organic chemist Bartlett) used this paradox to support a
radical new concept of organic mechanism.
The Hughes and Ingold paper was published in J Chem Soc
1935, 244-255. It proposed the duality of mechanism in organic
nucleophilic substitution reactions:
SN2 the classical deterministic model, in which ‘active’
substrate molecules are guided randomly by the thermal
jostling of the inert solvent molecules until a fortuitous ‘high
energy’ collision leads to the formation of an ‘activated
complex’ and subsequent reaction
SN1 a novel mechanism in which the solvent molecules arrange
themselves around one of the substrate molecules in such a way
that it facilitates the heterolysis of that molecule into an stable
solvated ion which takes no further part in the reaction and an
unstable solvated ion which eventually reacts either with a
solvent molecule (solvolysis) or the target molecule
(substitution).
CH3 \
CH3 -C – X
CH3 /
>
(CH3)3C+
+ X- + Y- > (CH3)3CY + X-
This mechanism requires a tendency of the organic moiety to
form a stable carbocation and strongly ionizing solvent
medium capable of temporarily stabilizing the carbocation
once formed (the leaving group X- is permanently stabilized by
the solvent molecules).
When using an 80 : 20 ethanol : water mixture as solvent, this
model correctly retrodicted that CH3CH2Cl and (CH3)2CHCl
would react slowly with the solvent and more rapidly if small
amounts of NaOH were added. It predicted that (CH3)3CCl
would react more rapidly with the solvent and that addition of
small amounts of NaOH would make no difference to the
reaction rate. In fact their experiments showed a slight but
significant fall in the reaction rate on addition of NaOH.
What was going on?
In these solvolysis reactions the rate of reaction is most easily
followed by “quenching” the reaction after various specific
times and measuring the amount of chloride ion generated by
precipitation with excess silver nitrate solution. This is a
measure of the rate of destruction of the halo-alkane. If the
reaction is following the SN2 mechanism the rate will vary with
both the concentration of halo-alkane and sodium hydroxide: if
however following the SN1 mechanism the rate should be
independent of the concentration of sodium hydroxide. This is
because the slow first ionization step is the rate determining step
of the reaction.
This anomaly caused the American physical organic chemist
Paul Bartlett to question the “SN2 fits all” paradigm followed
by all other US physical organic chemists of that time and after
some experimental work of his own on “caged molecules” he
threw his lot with Hughes and Ingold. As he remarked : “If
sodium hydroxide is a stronger reagent in some reactions and
water in others how can the fundamental mechanism be the
same?”
Hughes and Ingold would be aware of an important paper
authored by J D Bernal and R H Fowler, in the Journal Chem.
Physics 1, 515-548, (1933). In it the structure of water is
described as “Ice-like” < 4oC and “quartz-like” >4oC, with “4coordination” due to presence of TWO positive sites and one
negative site.
+H
O
=
+H
Simple disordered close packing of molecules of RMM 18 and
covalent radius 1.4 Ao would predict a density of 1.84 rather
than the observed 1.0. This illustrates how much space and
order exists in the liquid state of water. Because methanol and
ethanol possess only ONE positive site and one LESS negative
site, their structures must involve rings and chains:
CH3
CH3 CH3 CH3 CH3 CH3
OH --- OH -- OH -- OH -- OH -- OH
When alcohol molecules and water molecules are mixed in
roughly equal proportions there is a complete breakdown of
the “quartz-like structure” of the water component and the
consequent well-known shrinkage in volume of water-alcohol
mixtures.
The solvent used by organic chemists at the time for
nucleophilic solvolyses was an 80:20 ethanol-water mixture
(volume:volume). Because pure water contains 55.5 moles per
litre and ethanol only 17.1 moles per litre, an 80:20 volume
mixture contains roughly 1:1 mixture of MOLECULES.
For a typical 0.1 M haloalkane solvolysis, the molecular
proportions are:
1
: 111 : 137
Substrate : water : ethanol
So there are plenty of solvent molecules around to form both a
“solvent cage” round each substrate molecule as well as an
“inert medium” to facilitate mixing. According to the classical
theory, an “attacking” species like an azide ion (N3-) has to
jostle its way through the medium in its solvent cage propelled
by random collisions with solvent molecules until by CHANCE
it collides with sufficient energy in the correct geometric
alignment with a halo-alkane molecule to generate an
irreversible reaction.
N3- + (CH3)3CCl > (CH3)3CN3 + Cl-
In the case of solvolytic reactions, the classical theory suggests
that an energetic “free” water molecule must possess sufficient
energy to disrupt the “alcoholic” solvent cage surrounding the
hydrocarbon “end” of the haloalkane in order to initiate a
reaction (analogous to the azide reaction). Classical theory
would expect that the addition of 0.1M sodium hydroxide
(i.e. molecular ratios 1:1:110:137) would significantly raise the
reaction rate because (a) OH- ion is more reactive than H2O
molecule and (b) the ion does not have to “struggle” through
the solvent medium in order to collide with the target but can
move rapidly via rapid proton exchange. Ward found in 1927
this is exactly what happens when the target molecule is a
primary (RCH2X) or secondary (R1R2CHX) haloalkane but not
with a tertiary (R1R2R3CX) haloalkane. Ward found that the
reaction rates were identical for hydroxide and water: later,
more accurate experiments by Hughes and Ingold showed that
there was a small but significant DECLINE in the reaction rate
with OH- . What was going on?
Hughes and Ingold explained Ward’s original results as
follows: for tertiary haloalkanes there was a different
mechanism (the SN1 mechanism).
Hughes and Ingold in 1935 reported on but did not comment
on the slight reduction of reaction velocity when 0.1 M NaOH
was introduced into the reaction mix. However it was
commented on by Paul Bartlett in 1938 (J Amer Chem Soc ) as
a further justification for the SN1/SN2 concept. In 1952,
Hughes, Ingold and their research student T. Benfey
investigated the phenomenon more closely with other tertiary
substrates and concluded “that the attacking lyate ions (OH- or
OEt- ions) were waylaid by the exterior protons of the solvent
cage of the target molecule” ( J Chem Soc, 1952, 2494 )
All this shows that the effect of a mixed solvent which allows
differential solvation on the target molecule generates the
possibility of duality of mechanism: a classical deterministic
collision with the “attacking” species OR an indirect
mechanism where the solvent initiates heterolysis into two ionic
fragments in a slow, rate determining step followed by a rapid
classical attack by the “attacking species” on the positive
fragment.
The fact that the presence of OH- ions and their rapid proton
exchange chains hinders the attack of “free” water molecules
on the solvated carbenium ions while in turn they are
“waylaid” by the exterior protons of the solvent cage shows
that the reaction mix is behaving as a SYSTEM in which
PROCESSES occur, and the supposedly inert solvent can exert
a subtle directive effect. These results in 1927 encouraged
Hughes and Ingold to move away from the narrow
deterministic model popular at the time towards a more
process oriented model on Whiteheadean lines.