RECOMMENDED OPERATING PRESSURES
Why use different pressures for different solvents ?
A modern centrifugal evaporator gives the user a lot of control over the conditions within the
system as the solvents are being removed. This is important because the different solvents
used vary enormously in their key properties, and a single set of conditions cannot suffice for
all of them.
For every solvent there is an optimal set of conditions for removing it and the most important
of these parameters is the chamber pressure. All solvents have a boiling point which varies
with pressure, as illustrated in the graph below:
Boiling Temperature vs Chamber Pressure for Common Solvents
60
50
40
Boiling temperature (deg C)
30
20
10
0
0.10
1.00
10.00
100.00
1000.00
-10
-20
-30
-40
Pressure (mbar)
DMSO
DMF
Pyridine
Water
Toluene
IPA
Ethanol
Ethyl acetate
Methanol
Acetonitrile
TFA
Hexane
Chloroform
THF
DCM
Diethyl ether
Choosing the wrong pressure can have detrimental effects as follows:
•
If the system is programmed at too high a pressure (i.e insufficient vacuum),
evaporation may be slow, or final dryness poor.
•
If the system is programmed at too low a pressure (i.e. “too much” vacuum, as seen in
systems with no actual control over final vacuum level) then waste solvent recovery
will be low and pump wear may be increased. Some compounds may also sublime at
the end of the evaporation, resulting in poor yield.
•
If the rate of application of vacuum is not correctly set, then bumping (and cross
contamination) may occur, along with poor solvent recovery
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Operating Pressures
Understanding the condenser
The condenser removes heat from vapour that arrives from the chamber, causing it to
condense. To take heat from the vapour, the condenser must be colder than the vapour. If
the vapour’s boiling point is less than the coldest temperature in the condenser, the
condenser will never be able to cool the vapour enough to liquefy it. The more difference
there is between the coldest part of the condenser (the refrigerant) and the temperature at
which solvent condenses, the faster heat can be removed from the vapour and the greater
the available condensing power.
For example, methanol at 2 mbar boils at approximately -45oC. As the condenser in a typical
system is no colder than this, it will not be able to condense methanol vapour at this
pressure. (Heat will not flow out of vapour into a condenser that is no colder). At a higher
pressure, methanol will boil at a higher temperature, and a -45oC condenser will be able to
remove heat from the vapour faster.
Operating Pressure
A good rule of thumb is that the boiling point should never be taken below -20 oC. This
ensures that the condenser can always be significantly colder than the vapour, and it allows
us to define a good operating pressure for a given solvent just by looking at the BP/Pressure
relationship for that solvent.
This pressure has been tabulated for each of the common solvents, in the table at the end of
this document. It can be found in column C.
However, there are other values of pressure that are also relevant for each solvent.
Minimum pressure
Final Drying
There will be times when it is necessary to take the system pressure below the
recommended operating pressure for a given solvent.
The recommended operating
pressure applies to the bulk of the drying run but at the end of the run different rules apply.
Occasionally the sample is almost dry but to remove the final bit of solvent it is necessary to
drop the pressure further. The question is, how low should the pressure be dropped ?
Again, the answer for a given solvent can be found by looking at the boiling point/pressure
graph for the solvent(s) in question. If the pressure in the chamber is dropped so far that the
boiling point of the solvent drops below the condenser temperature, then even solvent which
has already been trapped and liquefied may re-boil and leave the condenser through the
pump. The net effect of this is that the pump will have to pump a large amount of vapour, the
carefully caught solvent will be lost again, and the system will not in fact go any lower than
this regardless of the target vacuum level.
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Operating Pressures
For example, after removing a quantity of methanol from samples at 11mbar, the user
decides to run a “final drying” stage. He (unwisely) drops the system target pressure to 1
mbar. But at 2mbar the methanol BP is -45oC and the solvent already captured starts to reboil in the condenser. The system pressure will then not actually go below 2 mbar as the
pump tries to deal with this newly formed vapour, and a large volume of methanol vapour will
be lost through the pump.
The user could have achieved exactly the same drying performance by specifying a value no
lower than 2 mbar. But methanol would have remained in the condenser rather than going
out through the pump, which is preferable for the environment and for system life.
We refer to 2mbar as the “Minimum pressure” for methanol.
Solvent Mixtures
In the scenario outlined above, the pressure was dropped below the operating pressure at
the end of the run to achieve good dryness. However, there is another scenario where the
“Minimum pressure” comes into play.
If this had been a mixture of methanol and DMSO, it might be expected that the system
should be run at full vacuum (to remove the DMSO) but in fact the system would not go
below 2 mbar due to the methanol (for reasons explained above) and so it would be futile
setting full vacuum as the target pressure.
(In this instance, the only successful strategy is to remove the methanol, then stop the run
and drain the condenser, then re-start the run at full vacuum and remove the DMSO. This
happens automatically with an autoswitching condenser).
For most volatile solvents, there is a minimum pressure that it is futile to go below during a
run. This is tabulated in column D of the table at the end of this document.
An example of how to apply this is as follows.
If the system were to be used to dry a mixture of toluene and THF, what pressure should be
selected ? Toluene alone has a recommended operating pressure (column C) of 3 mbar,
but THF has a minimum pressure of 5 mbar. Therefore with this mixture the system must
not be programmed below 5 mbar or all the THF will be boiled out of the condenser and sent
through the pump. And inevitably the toluene will be slow to remove.
The V2.0 Auto-Program function gets this kind of thing wrong !
In V2.0 software the auto-program function takes no account of minimum pressures.
(Though later versions may address this). So you may need to correct an “autoprogrammed”
run for this reason. Be vigilant.
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Operating Pressures
Preventing Freezing
There is a third reason why it is important to correctly control system pressure. Some
solvents (such as water) have relatively high freezing points. What this means is that it is
possible to accidentally cause the water in a solution to freeze by lowering the boiling point of
the solvents present below 0 oC. If the only solvent is water, then the freezing is prevented
by ensuring the water boils at > 0oC, which means ensuring that the system pressure is
above 6 mbar. (in fact we choose 8 mbar for water, for reasons explained at the end of this
document).
When the solution is a mixture containing volatile solvents as well as water, it is necessary to
ensure that the other solvents do not boil below 0 oC so that freezing of the water is not
caused when the volatile solvent is boiling.
For this reason, column B of the table at the end of this document shows the pressure at
which each solvent will boil at 0 oC.
This tells us (for example) that acetonitrile should not be removed from an acetonitrile/water
mixture at less than 35 mbar, otherwise the solution will be cooled to less than 0oC and
freezing of the water may occur. (This in contrast to a pure acetonitrile solution, which could
be evaporated at 11mbar).
Column B shows for a range of solvents what operating pressure would be advisable if the
solvent was in a mixture with water.
Other Freezing Points
Water freezes at 0oC, which is well known.
It is not only water that can freeze. In the column marked “FP” the freezing points of the
common solvents are listed.
This column is relevant for two reasons.
•
It tells you which solvents need a defrost. (Any FP above -40 will probably freeze in
the condenser)
•
It warns which other solvents (as well as water) will benefit a 2 stage run when mixed
with a volatile solvent. That is to say, acetonitrile/acetic acid offers the same sort of
challenge as acetonitrile/water. More so, in fact, because acetic acid freezes at a
higher temperature than water.
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Operating Pressures
Bumping
There is a fourth consideration when choosing the pressure for a given solvent or a mixture,
and that is how best to specify a vacuum ramp to prevent bumping.
When a mixture is deemed to be at risk of bumping, the recommended action is to use
DriPure™ which means a carefully ramped vacuum and a higher rotor speed (more
centrifugal force). A standard vacuum ramp exists which is a good “catch all” design for a
range of solvents, but for any one solvent it may take an unnecessarily long time. Time can
be saved by tailoring the vacuum ramp to the particular solvent in question.
When the vacuum is progressively applied in an evaporator, the onset of boiling happens at a
particular pressure, which can be deduced based on
•
Which is the most volatile solvent in the mixture
•
What the temperature of the solution is just before boiling commences
The temperature of the solution at the moment before boiling commences is likely to be close
to the temperature of the chamber because the air inside the chamber undergoes a lot of
turbulent mixing as the rotor spins up and this will pass heat between the chamber and the
samples. If the system has just been turned on after being off overnight then the chamber
may be at exactly room temperature but it is a good bet that if the system has been on it is up
at 30 degrees or more.
Why choose a solvent specific Vacuum Ramp ?
Vacuum ramping is intended to soften the transition into boiling, so that the solution can
gently achieve a steady state with heat being smoothly convected from where it is supplied
(usually towards the base of the vessel) to where solvent is boiling (at the free surface). If
the pressure is falling too rapidly then this transition may be too sudden, causing boiling to
happen below the surface of the liquid.
However, if the transition into boiling happens at (say) 200 mbar, there is no benefit
whatsoever in gently ramping the vacuum from 500 down to 220mbar – during that phase of
the pumping down, there will be no sudden boiling however fast the vacuum falls.
This means that in order to choose the optimal vacuum ramp it is important to know at what
pressure the solvents present will start to boil. Column A of this table shows typical minimum
ramp starting points based on a 30oC solution (it is advisable to start the ramp up to 10mbar
above these figures) for each of the solvents listed. The ramp should start at the highest
pressure of any of the components.
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Operating Pressures
Typically a solution will not bump below 50 mbar, so a ramp need not continue much below
this to prevent bumping. In terms of ramp rate, it is a good rule of thumb that the ramp
should be no steeper than 10 mbar per minute.
Example:
The mixture in question is acetonitrile and chloroform. An acetonitrile ramp would start
above 150mbar but the ramp for choroform must start above 290mbar. So for good
measure, a mixture of these two solvents should ramp from 300mbar down to 50mbar. The
duration should be (300-50)/10 = 25 minutes.
Is a vacuum ramp necessary for every solution ?
Not all solutions are at risk of bumping. If in doubt, however, take anti-bumping precautions
whenever you have
•
a mixture of solvents
•
a solvent with a very low BP (DCM, diethyl ether)
With a ramp suited specifically to the solvents, the amount of time lost by specifying a ramp
unnecessarily is fairly small (compared to the cost of lost samples if you did not take
precautions and bumping occurred). So if in doubt, use variable DriPure™.
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Operating Pressures
Table of Key Pressures (in mbar)
A
B
Ramp
Start
Pressure to boil at
this Temperature
C
Water
mix
D
Operating
pressure
Minimum
pressure
Recommended
operating
pressure
FP (oC)
30oC
0 oC
-20 oC
-45 oC
Acetic Acid
28
5
N/A
N/A
16.6
14
Acetonitrile
150
35
11
2
-43.8
11
Chloroform
290
70
23
5
< -45
23
DCE
120
25
8
1.5
-35.5
8
DCM
700
180
60
13
< -45
60
Diethyl ether
840
240
85
20
< -45
85
6
1
Full vac
Full vac
< -45
Full vac
DMSO
1.5
Full vac
Full vac
Full vac
18.5
Full vac
Ethanol
90
15
4
0.5
< -45
4
Ethyl acetate
150
33
10
2
< -45
10
Formic Acid
75
15
N/A
N/A
8.3
25
220
55
18
4
< -45
18
75
11
2
0.25
< -45
2
Methanol
205
40
11
2
< -45
11
TFA
190
40
12
2
-15.2
15
THF
275
70
23
5
< -45
23
Toluene
50
10
3
0.5
< -45
3
Water
40
6
N/A
N/A
0
8*
DMF
Hexane
IPA
(*) See end of this document for explanation of why not to specify 6mbar or Water.
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Operating Pressures
Why do I see vac ramps that go all the way to target vacuum ?
Earlier in this document it is stated that below 50mbar bumping is probably not going to
happen so a ramp to prevent bumping can stop there. Yet some systems are quite
deliberately programmed with the ramp going all the way down to the target vacuum. Why ?
The main reason is for solvent recovery. Any rapid decrease in pressure after the boiling of
the solvent has started will cause a burst of rapid boiling which for a short period my
“overwhelm” the condenser, causing some solvent to go through the pump and perhaps be
lost to the extraction system. Therefore by ensuring there is never any sudden decrease in
pressure, it is possible to give the condenser an easier time.
This means that even though continuing a ramp all the way down to 8 mbar (or whatever the
target pressure is) is no better for bumping than stopping the ramp at 50 and then going
straight to the target pressure, it may have advantages for solvent recovery.
Why dry Water at 8 mbar rather than 6 mbar ?
When a tube of water is evaporating in a Genevac, vapour boils away from the top of the
tube, while heat is mostly supplied at the bottom. If it is boiling at the top at 4 oC (8 mbar),
then it might be 5 or 6 or more degrees at the base of the tube. As the water increase above
4oC, it gets less dense and so a convection circulation forms which carries the heat up to the
top of the tube.
If we imagine the same situation at a boiling temperature of 0 oC (6 mbar), we have a slight
problem. Water is at its most dense at 4oC.
Warming water up from 0 to 2 oC makes it more dense so will not immediately lead to
convection. When the base of the tube gets hot enough, (maybe 8 degrees) then the warm
water at the base will be less dense than the cooler water at the top, but this will mean
sporadic and chaotic convection flow rather than smooth continuous circulation, which will in
turn give slower and less efficient heating.
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