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Hydrogen
bonding
at
high pressure
J. S.
LOVEDAY
Department
of
Physics
and
Astronomy
and
Centre
for
Science
at
Extreme
Conditions
The
University
of
Edinburgh
-
Mayfield
Rd,
Edinburgh
EH9
3JZ,
Scotland,
UK

other H-bonded solvents
are
crucial
in
chemistry, H-bonds
and
their directional
nature
are
responsible
for the
structural
versatility
of ice
giving
rise
to at
least
eleven
phases
below 2GPa, hydrogen bonding plays
an
important
role
in
determining
the
dehydration properties
of
hydrous minerals, implicated

ubiquity provides
a
very
powerful
motivation
to
understand
the
microscopic behaviour
of
hydrogen bonding, including,
the
relationships between
bonding
strength, atomic species
and
bond geometry [2].
2.
—
Definitions
Figure
1
shows
a
schematic
of a
hydrogen bond. Atom
A is
covalently bonded
to

and
vibrational
properties.
The
principal criterion
is
that
the H • • • B
distance
is
less than
the sum of
the van der
Waals
radii
of H and B
—taking
the
value
for H to be 1A
[3].
In
addition,
there
is an
expectation
that
the A-H
stretch vibrational mode should
soften

(upper)
and
short
(lower)
H-bonds.
the A-H • • • B
libration mode should
stiffen.
For
long hydrogen bonds
the
interaction
is
considered
to be
largely ionic between
a
somewhat positive hydrogen atom —indicated
by
a 8+ in fig. 1— and a
somewhat negative atom
B
—indicated
by a 6—. As
hydrogen
bonds
shorten,
they develop
a
more covalent character with transfer

need
not be an
atom;
it
may
be an
accumulation
of
electron density
as in
ethyne
where
C-H
forms
H-bonds
to
the
carbon-carbon triple bonds [4].
3.
—
Techniques
The
principal microscopic
properties
needed
to
characterise
a
hydrogen bond
are its

diffraction
studies
to
characterise
the
geometry,
and ab
initio modelling studies
that
explore
the
nature
of
the
bonding. Other techniques like nuclear magnetic resonance
and
neutron inelastic
scattering
have proved very
powerful
for
studies
of
H-bonds
at
ambient
pressure
but
have
not yet

to the
incident light
via a
change
in
dipole
moment
(infra-red)
or
polarisability (Raman).
The
attraction
of
such measurements
is
that
the
softening
of the A-H
stretch mode
(referred
to
here
as the
vibron)
is one of the
primary indications
of
strengthening hydrogen bonds,
and

been
to
explore short H-bonds close
to
molecular dis-
sociation. Under these conditions
the
vibron moves into regions where diamonds have
absorption bands
and
interaction
between
the
vibron
and
other
vibrational
modes
be-
comes
significant. However, innovations
in
cell
design, improvements
in the
quality
of IR
data
made possible
by the use of

of
states
[9] and
X-ray
nu-
clear
spectroscopy measurements
of
partial density
of
states
[10].
For
H-bonded systems
however,
the
vast bulk
of
spectroscopic
data
are
obtained using photons.
For
this rea-
son
the
term spectroscopic used
in
this lecture
refers

system. Although X-ray studies
are
able
to
locate hydrogen atoms
and can
identify
the
H-bond
contacts
in a
structure, neutron diffraction
is the
only technique
able
to
measure
the
geometry
sufficiently
precisely. Studies
of
H-bonded systems were
a
primary
motivation
of the
development
of
high pressure neutron

systems. Studies
of
dissociation
of
H-bonds
in
simple molecular solids remain
an
important motivation
for
further
extensions
of the
pressure range.
3'3.
Ab
initio modelling.
- The
capabilities
and
accuracy
of ab
initio modelling studies
have
seen remarkable recent improvement.
Two
basic methods exist
to
carry
out

studies
of
H-bonding [13,
14] but are
limited
by the
difficulty
of
handling disorder.
The
development
of ab
initio molecular dynamics (the Car-Parrinello method) [15] overcomes
this limitation
and has
revolutionised modelling
of
H-bond systems.
In
this
method,
the
time evolution
of the
system
is
followed
with
the
motion

obtained. Theoretical studies
are
generally
not
able
to
identify
the
structure
ab
initio, however,
and
require structural information
as a
start
point.
360
J. S.
LOVEDAY
5 10 15 20
P(GPa)
25
Fig.
2. - The
measured
pressure
variation
of the
intramolecular
O-D

solid phases adopted
by the
water molecule have become model systems
for
studies
of
H-bonding
at
high pressure.
At the
molecular level water
is one of the
simplest
H-bonded
systems since H-bonds
are the
principal
attractive
interaction.
As a
result
of
this
and
because
of the
fundamental interest
of the
water molecule,
ice has

strong reduction
in the O-H
vibron indicating
a
weakening
of the
(covalent)
molecular
bond
and a
strengthening
of the
hydrogen bond [17].
In the
absence
of
direct
measurements, estimates
were
made
of the
extension
of the
covalent
O-H
bond length
resulting
from
this weakening. This approach requires
an

left-
hand plot) describing
the
interaction
of the
H-atom with
the
donor
and
acceptor oxygen
atoms, respectively. This assumption
of
pressure-independent two-atom potentials
im-
plies
that
as the
H-bond compresses
and the
acceptor atom moves closer
to the
hydrogen
the
attraction
of H by the
acceptor causes
the
covalent
O-H
bond

H-bonded materials
at
ambient pres-
sure
[3].
The first
structural study carried
out
with
the
Paris-Edinburgh cell, studies
of
ice
VIII, tested this assumption
and
showed
that
the
intramolecular bond length
was
essentially unchanged
by
pressure
up to at
least 25GPa (fig.
2)
[18, 19]. This lack
of
HJ.YDROGEN BONDING
AT

two-atom
O-H
potentials
(left-hand plot) describing
the
interaction between
the El-
atom
and the
donor
and
acceptor oxygen
atoms.
This
approach
and the
assumption
of a
lack
of
change
in the
two-atom
potentials
with
pressure
underlies Klug
and
Whalley's
[17]

essentially
the
opposite
of
that
which
had
been assumed.
Two
total-energy
studies reproduced
the
observed behaviour
of the O-H
bond length
and
confirmed
this
view
of the
changes
in the
potentials [13, 14].
More
recent
ab
initio molecular dynamics
studies
of ice
also produce

an
important
goal
since
it was first
postulated
by
Ubbelohode
in
1949 [24].
The
search
for ice X
has led to
extensive revisions
of the ice
phase diagram
in the
very
high pressure region
throughout
the
1990's. Pruzan
et al.
[25] discovered
that
the
transition temperature
of
the

for
other H-bond ordering
transitions.
In
1996
IR
studies
by
Goncharov
et
al.
[5] and
Aoki
et al.
[26] reported
the first
evidence
of a
symmetrisation
transition
at
~ 75
GPa.
The
manifestation
of the
transition
appeared more complex
than
previously

range
75–110
GPa.
Ab
initio modelling
by
Benoit
et al.
[27] also showed
a
symmetrisation
transition
starting
at
similar pressures where
the
volume explored
by the
proton increases
as the
result
of
362 J. S.
LOVEDAY
quantum
effects.
This study
found
an
intermediate

As a
result,
it
appears
that
symmetrisation
occurred progressively
in the
range
65–110GPa
[28].
4'2.
Disorder
in ice
VII.
–
These revisions
of the
phase diagram have
established
the
importance
of
proton-disordered
ice
VII.
In
addition
to
dominating

found in
ordered
ice
VIII [29]. Such
a
change
cannot
be
real
(it
would
liberate enough energy
to
melt
the
sample)
and so it has
been assumed
that
the
oxygen
atoms were multi-site disordered. However,
the
model proposed
by
Kuhs
et al.
[29]
—O
displacement along

two
different
H-bond lengths
~ 0.1 A
longer
and
shorter than those
of ice
VIII
and
that
this
significant
difference
is
pressure independent
up to at
least
20
GPa.
This
raises
the
question
as to how
such
a
mixed network
will
symmeterise

stretch
peak
which
is not
observed even
in
dilute
H in D2O
experiments
which
probe uncoupled
O-H
vibrations [17]. This suggests
that
the
simple
view
of a
direct
correlation between
H-bond
length
and O-H
stretch
frequency
may be
incorrect. This unexpected disorder
model
also raises
the

studies
of ice VII by
Loubyere
et al.
[31]
revealed
that
the
structure
has an
incommensurate superlattice
that
persists
across
its
entire range
of
existence
and
into
that
of ice X.
This
superlattice
is not
observed
in
either X-ray
or
neutron powder

of a
mode crossing (Fermi resonance).
Ab
initio
molecular-dynamics studies
by
Cavazonni
et al.
[32] explored
the
behaviour
of H2O at
the
high
pressures
and
temperatures
found
within Uranus
and
Neptune. They
found
evidence
for a
dissociation
of the
molecules
and
protonic conduction
that

as
ices; water
ice is the
most studied
of
this class. Studies
of
other systems provide
a
means
to
explore
the
effect
of
changing
hydrogen bond strength
and
H-bond geometry.
5'1. Ammonia.
-
Ammonia
forms
weaker hydrogen bonds than water
and has an
unbalanced geometry
in
that
it has
three donor

al.
[34]
in
X-ray studies
found
a
hexagonal close-packed nitrogen arrangement between
3 and at
least
30
GPa.
As a
result,
it was
assumed
that
like
the
low-pressure solid
phases
II and
III, phase
IV and
possibly phase
V had
rotationally disordered molecules.
However,
neutron
diffraction
studies showed ammonia

found
this
structure
to be
stable
to
above
100 GPa
and,
like
ice
VII,
to
become
a
protonic conductor
at
high temperatures
and
pressures.
5"2.
Hydrogen
sulphide.
-
Hydrogen sulphide
has the
same internal molecular geometry
as ice but
much weaker hydrogen bonding;
its

GPa,
11 GPa and 27
GPa,
and
that
metallisation
may
364 J. S.
LOVEDAY
be
the
result
of
short
S-S
contacts
which
are not
H-bond
contacts
[38,39].
The
relationship
between
the
primitive cubic phases
II and I' is
also
of
relevance

that
the
maxima
in the D
density
point towards
six of the
twelve nearest-neighbour atoms.
The
displacement
of the
sulphur
atoms
from
fee
sites
reduces
the S • • • S
distance
for six
neighbours
and
lengthens
it for the
other
six.
This
arrangement
suggests
the

I' but
found
the
phase
I to IV
transition
to be a
progressive ordering driven
by
H-bonding [41]. Fujhisa
and
co-workers [42] have recently
found
new
phases
in
what
had
been assumed
to be the
stability
field of
phase
IV
below
10 GPa at low
temperatures. These phases
may
also
reflect

in
addition
to
their fundamental
interest.
6"1.
Alkali
hydroxides.
-
Potassium
and
sodium hydroxides
sit on the
boundary
of
hydrogen
bonding.
KOH
exhibits hydrogen bonding
that
strengthens with increasing
pressure. NaOH
is
only H-bonded
at low
temperatures [43]
and
spectroscopic studies
show
that

hydroxides.
- The
brucite-structured hydroxides
are a
model
system
for
H-bonding
in
hydroxyl-containing systems. They have layered structures
where
the
dominant interactions between
the
metal-oxygen layers
are the
H-bond inter-
action
and
repulsive interactions between
the
hydrogen atoms [23]. Mg(OH)
2
, brucite,
shows
a
softening
of the
vibron with pressure indicating
a

increased
in
brucite
the
displacement
of
H(D)
from
the
threefold axis increases. Similar behaviour
is
observed
in
Mn(OD)
2
,
Ni(OD)
2
and
Co(OD)
2
[47].
Raman
and IR
studies
of
Co(OH)2
revealed
that
the

that
in
Co(OH)
2
only
the
H-sublattice
amorphises.
However,
Parise
et al.
[23] showed
from
neutron
data
collected
HYDROGEN
BONDING
AT
HIGH
PRESSURE
365
from
Co(OD)2
that
the
occupancy
of the
D-site remained
fully

symmetry
of the
D-site.
The
need
to
main-
tain
a D • • • D
distance
of
more
the 1.8 A
forces
the
D-atoms
to
occupy general positions.
This means
that
the
D-atoms have
a
wide
range
of
different
bonding environments that
could
account

single-
component systems. Mixtures provide
a
means
to
probe phenomena like repulsive
in-
teractions
and
mixed H-bonds
that
are not so
readily accessible
and
mixtures
may
yield
analogous structures
that
provide insight into
the
parent single-component systems.
A
classical water-gas mixture
is the
clathrate-hydrate where
the
guest
gas
molecules

are too
small
to
form
cage clathrates
and the
discovery
that
helium
forms
a
hydrate structure based
on
that
of ice II
caused considerable surprise [50].
Vos et al.
[51] explored
the
hydrogen water
system
and
found
an ice II
related hydrate which appeared
to be
similar
to
helium
hy-

2
• H
2
O is
approximately
twice
as
compressible
as ice VII and
spec-
troscopic studies suggest
that
the
network
of
H-bonds
may
undergo symmetrisation
at
~ 30 GPa
[52]. Although these mixtures
are
called clathrates, their structures
do not
have
cages
and
resemble
ice
structures very closely.

those
of
methane, nitrogen, oxygen
and
carbon dioxide
it is
also directly relevant
to
modelling
of the
Earth
and
other planets. They have been extensively studied
in the
0–1 GPa
range; phase transitions have been reported
in
argon, methane
and
nitrogen
hy-
drates [53–56].
However,
very
little
work
had
been carried
out at
pressures above this

studies
of
methane hydrate revealed
two new
phases [57].
The first is a
hexagonal hydrate stable between
0.8 GPa and 1.9 GPa
with
366 J. S.
LOVEDAY
a
methane: water
ratio
of
3.5(5):1.
This
phase
was
confirmed
in
X-ray single-crystal
studies
by
Chou
et al.
[58].
The
second phase
is

is
somewhat
distorted
compared with
that
of ice Ih in
order
to
expand
the
channels
to
accommodate
the
methane molecules,
but the
network
is
very like
those
of the filled
ices. Hydrogen
and
helium
do not
form
cage clathrates
and
methane
hydrate

accreted
from
a
mixture
of
rock, methane hydrate
and
ammonia monohydrate [60]. Current
models assume
that
all the
methane
was
expelled
from
Titan
early
in its
history
as a
result
of the
assumed pressure decomposition
of
methane hydrate [61]. This resulted
in the
need
to
postulate
some

The
stability
of
high pressure methane hydrates means
that
the
methane
may
have
remained within
the ice
mantle
of
Titan
as
methane hydrates
and
that
this
is the
reservoir
supplying
the
atmosphere with methane.
7'3. Ammonia
hydrates.
- The
three ammonia hydrates
are
amongst

Titan
and the
assumed waterrammonia
ratio
in
Neptune
and
Uranus
(~
15%) corresponds
to a 1:1
mixture
of
water
and
ammonia dihydrate. Fur-
thermore, ammonia monohydrate
is
predicted
to
ionise
to
form
ammonium hydroxide
at
~ 13 GPa
[62].
Raman studies suggested
that
there

AMH
revealed
that
there
are
seven phases
up to 6 GPa
[66].
In
general
these
phases have
rather
complex
diffraction
patterns
and
presumably complex
structures.
The
exception
to
this
is
phase
VI,
which
is
formed
by

substitutionally disordered
so
that
each molecular centre
is 50%
occupied
by
water
and
ammonia.
AMH-VI
is
thus
a
type
of
material:
a
hydrogen-bonded
molecular alloy (see
fig. 6).
There
is
also evidence
of
repulsive
effects
like those
found
in

denote H-bonds.
The
larger spheres
in (a) are the
methane molecules. MH-III
is
viewed approx-
imately along
its
a-axis
and ice Ih
approximately along
a
[110] direction. Right:
the
structure
of
(c)
MH-III
and (d) ice Ih
viewed parallel
to
their c-axes.
The + and —
symbols show
the
sense
of
c-axis H-bonds
from

AMH-VI
and its
similarity
to ice VII
raises
the
possibility
that
it
forms
a
solid
solution with
ice VII so
that
the
relevant phase
for the
interiors
of
Uranus
and
Neptune
may
be a
water-rich variant
of
AMH-VI.
8.
—

for
tackling complex H-bonded systems. Such complex systems
are one of the
current
grand challenges
for
high-pressure studies
of
hydrogen bonding.
* * *
I
would like
to
thank
R.
NELMES
and R. J.
HEMLEY
for
reading this manuscript
and for
their
helpful
suggestions.
I
also acknowlege
the
support
of the
Engineering

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J. S.,
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R. J.,
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R. J.,
Science
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J. S. and
NELMES
R. J.,
Phys. Rev.
Lett.,

in
organic chemistry.
The
creation
of new
molecules
by
new
chemical routes
and new
activation processes highlights
the
power
of
organic
chemistry.
Two
major objectives must constantly
be
kept
in
mind: yield
and
selectivity.
It is
evident
that
chemical synthesis
is
optimal when highest yield

and may be
divided essentially into physical (temperature, pressure,
light)
and
chemical (catalysis) activation methods. Pressure activation
is,
basically,
not
a new
technique although
the first use of
this
parameter
in
chemistry
dates
back
from
1892 only [1]. Sporadic reports
on
high pressure synthesis were published [2]; however,
the
technique became popular mostly
in the
last
twenty years.
The
fundamental
effect
of

Fig.
1. -
Pressure
acceleration
of
rate
constants.
Ay* is the
activation volume.
It is
stricto sensu
the
difference
in
partial
molar volumes
of
transition
state
and
reactants. This kinetic parameter
is, in
fact,
the
basic parameter
to be
considered
for
synthetic purposes.
It is

of
rate
constants
for two
values
of
AV*.
A
number
of
name
reactions
have been
investigated
under
pressure
and
their
activa-
tion volumes determined. Table
I
lists representative values.
Such
values take into account
the
volume variations resulting
from
molecular reorgani-
zation (bond cleavage
and

3
mol
–1
at the
maximum.
The
additional volume value
is
ascribed
to
solute-solvent interactions
which
are
overwhelming
in all
ionogenic reactions.
Other
possible volume
effects
can
result
from
steric interactions since
the
pressure
sensitivity
of
reaction
rate
was

ORGANIC
SYNTHESIS:
OVERVIEW
OF
RECENT
APPLICATIONS
375
-
formation
of one or
more bonds,
-
generation
of
charged species,
-
steric hindrance.
Considering
high pressure
as
activation mode,
the
best yields
are
obtained when
the
rate constant
is not too low at
ambient pressure (though notable exceptions
are

properties
of the
liquid molecular system.
-
Pressure increases
the
solubility
of
solids
and
miscibility
of
liquids
in any
medium.
This
is
important
as it may
influence
the
homogeneity
of the
medium.
-
Pressure increases
the
viscosity
of all
liquids

of the
solidification
point
can be
made
from
application
of the
equation
of
Simon
and
Glatzel [5]:
a, c :
constants
TO :
critical temperature.
TABLE
I. -
Experimental activation volume values
for
given reactions.
Reaction
AV*
(cm
3
mol
–1
)
Concerted

melting
points
(in
°C).
Compound
Acetonitrile
Ethanol
Diethyl
ether
Dichloromethane
Chloroform
Carbon
tetrachloride
Dioxan
Ethyl
acetate
Chlorobenzene
Nitromethane
Nitrobenzene
Cyclohexane
at 0.1 MPa
-43.9
-117.3
-116.0
-96.7
-63.5
-22.6
-0.2
-83.6
-45.5

MPa
111.6
-37.7
20.6
2.2
79.1
81.4
4.5
85.7
111.4
Some
useful
calculated
Tp
values
for
common solvents
are
listed
in
table
II. The
importance
of the
liquid
state
has
recently been highlighted
in the
Henry addition

state
of the
reactional system
at the
working pressure
and
temperature.
2.
—
Recent
applications
2'1.
Cycloadditions.
-
Cycloadditions
are
typical examples
of
pressure-accelerated
reactions, particularly those showing reluctance
to
occur
at
ambient pressure
due to
steric
B
CN
R,
DR

COOMe
Fig.
3. -
Synthesis
of
ßlactams
via
high pressure
[2 + 2]
cycloaddition
of
enol
ethers
and
isocyanates.
hindrance
or for
electronic reasons.
In
this section
we
will
give
a
nonexhaustive overview
of
recent applications
in
this
field

). However, depending
on
sub-
strates
the
transition
state
can be
more polar than
the
initial
state
in
such
a way
that
electrostrictive
effects
generate
an
additional
volume
term
making such
reactions
fairly
to
strongly pressure sensitive.
As an
example, enol ethers

yield
is 90%
(no
reaction
at 0.1 MPa in
both cases). Even, silyl enol ethers
can be
used
in
uncat-
alyzed
reactions
at
high pressures where only
low
yields
of
cyclobutanes
are
obtained
at
normal pressure
in the
presence
of
Lewis acid
catalysts.
An
interesting application
of

pressure process.
In
the
same way,
2,3-dihydrofuran
reacts with phenyl isocyanate
at 100 °C
under high
pressure. Eighty percent yield
of the
corresponding
ß-lactam
is
obtained
at 800 MPa
[9].
A
related reaction concerns
the [2 + 2]
cycloaddition
of
2,3-dihydrofuran
to
Schiff
bases
(fig.
4)
[10].
The
reaction

cyclooctyne.
in
virtue
of the
formation
of one
bond
and a
zwitterionic intermediate
in the
transition
state.
Yields
of
azetidines
are
modest
to
good.
2'1.2.
[4 + 2]
Cycloadditions. These reactions
are
generally concerted (simultane-
ous
formation
of two
bonds
in the
transition

react with cyclooctyne
to
give stable bridged cycloadducts (20–80%
at
800MPa, 90°C,
10
days) (fig.
5)
[11].
Furans
show
strong reluctance
to
enter cycloaddition.
The low
reactivity
is
ascribed
to the
easy retro-Diels-Alder process
where
the
aromaticity
of the
diene
is
recovered.
High
pressure
is an

used
for
further
synthesis
of
highly
functionalized hydrinde-
nones.
These compounds
are key
intermediates
for the
preparation
of
ottelione
A, a
potent inhibitor
of
tubulin polymerization (fig.
6)
[12].
At
normal pressure Lewis acid
catalysis leads
to
Michael adducts only.
Palasonin
is an
inhibitor
of

Two-step
synthesis
of
palasonin.
effected
very
efficiently
by
high pressure cycloaddition
of
citraconic anhydride
to
furan
followed
by
hydrogenation (fig.
7)
[13].
The
reaction
was
also used
for the
partial
synthesis
of a
complex molecule, paclitaxel.
The
CD-ring
is

tethered
furans.
2-methylfuran
at
1500
MPa
affords
two
stereoisomers (1:1) (90%)
which
are
immediately
hydrogenated
in
order
to
avoid reverse
reaction.
In the
same way,
other
furans
and
maleic
anhydrides
can be
brought
to
reactivity. Figure
8

lactones—is also
promoted
by
application
of
pressure.
Intramolecular Diels-Alder reactions
of
furans
are
also strongly accelerated
by
pres-
sure.
Complex structures have been obtained
by
reacting
furans
tethered
by
bicyclo-
propylidenes
(fig.
9)
[15].
A
key
step
in the
synthesis

skeleton
can be
constructed
in one
step
via [4 + 2]
cycloaddition
of
activated pyrroles with dienophiles. High pressure activation
permits
to
extend
largely
the
scope
of
these reactions [17].
A
particularly interesting application
is the
synthesis
of an
analogue
of
epibatidine
which
is a
potent analgesic. This
is
achieved

O
Fig.
10. -
Intramolecular
Diels-Alder
reaction
of 3.
R
= H
yield: 100% (0.1 MPa)
R
= Me
yield:
53%
(1000
MPa)