III.Schlenk Line and Schlenk Flask: General Tips
1. Familiarize yourself with the state of the art technique by reading one of the recommended references below. The books by Shriver and the last chapter in Brown's book are especially recommended since they should give an overview of almost all the techniques one would have to learn. The other articles are somewhat supplementary and pertain to specific types of equipment. One reading is undoubtedly not enough. The best thing is to periodically read while actually gaining hands-on experience.
2. When attempting the first few experiments ask someone to demonstrate basic skills and manipulations. Try to "rehearse" the actual experiment in your mind especially when you feel you lack the experience. Train yourself to ask at which points during the manipulation can things go wrong. Also, mentally devise ways to minimize exposure to moisture or oxygen. Develop an intuitive sense for foreseeing events during the experiment. Experience, trial and error (hopefully minor) are the best teachers in attaining expertise.
3. Compounds which are sensitive to less than 10 ppm oxygen are normally best handled in a glovebox.1,2 A practical thing to think about when doing an experiment is to decide which parts of the experiment can be done in and out of the glovebox. In this way, the two methods complement one another. A cardinal rule to keep in mind is that there are many things that one cannot place in the glovebox (halocarbons, volatile phosphines, etc) in view of their undesirable qualities. To supplement this need one can resort to using a polyethylene glovebag.
4. A two-way manifold, usually consisting of three or four gas inlet/outlet stopcocks provides the most basic equipment for Schlenk work. The vacuum/nitrogen cycle is the heart of minimizing the amount of oxygen in a Schlenk vessel and should be done at least three times. Try to maintain a steady N2 flow through the manifold, particularly when opening vessels to the atmosphere. (This is best monitored by watching the flow of N2 gas through a bubbler.) When maintaining a positive flow, attempt to maintain "laminar" flow of gas.1 Try to moderate changes between vacuum and N2 gas cycles; avoid sudden large changes in pressure. Do not rush, particularly at times when patience appears to be the limiting factor.
5. Expand your knowledge by reading relevant portions of the experimental sections in published papers. These are especially useful for learning new short cuts and ideas.
References
1.Shriver, D. F. "The Manipulation of Air Sensitive Compounds"; McGraw-Hill: New York, 1969. Chapter 7 is a good place to start reading.
2.Shriver, D. F., Drezdzon, M. A. "The Manipulation of Air Sensitive Compounds"; 2nd ed., Wiley: New York, 1986.
3.Kramer, G. W.; Levy, A. B.; Midland, M. M. In Organic Synthesis via Boranes; Brown, H. C., Ed.; Wiley-Interscience: New York, 1975.
4.Gill, G. B.; Whiting, D. A. Aldrichimica Acta 1986, 19, 31.
5.Burlitch, J. "How to use Ace No-Air Glassware", Bulletin 3841, Ace Glass Inc.
6.Wayda, A. L.; Dye, J. L. J. Chem. Educ. 1985, 62, 356.
IV.Filtration Methods
B.Suction Filtration
To perform suction filtration in the drybox, a filter flask fitted with an O-ring adapter and a glass frit is securely clamped to a ring stand. Vacuum is applied to the side arm of the filter flask . A T-tube assembly (Figure 1) is connected to the filter flask via one of the two available hose outlets. (It is assumed that a liquid N2 trap has already been set-up and the pump has been turned on. If a sample is already being dried under vacuum prior to filtration, it is wise to place that sample under N2 via the T-tube assembly before you start filtration to prevent possible contamination of that sample.)
To begin filtration, check if the T-tube is in the "closed" position (Figure 4-1). Turn on the "main" vacuum source at the back of the dry box. Gradually bring the T-tube stopcock into the "open" position after placing enough solution in the frit. Upon completion of the filtration, make sure that any previous samples being dried are returned to vacuum. If no samples were previously connected to the T-tube, return to "closed" position and turn off the main valve on the drybox wall.
B.Pressure Filtration
1.Glass Frit
This method is a quick alternative to suction filtration for filtering small quantities of solution (≤ 20 mL). Fill a glass frit, securely mounted in a clamp, approximately half full with your solution. A rubber pipet bulb is inserted into the glass frit until a seal is made (Figure 4-2). Gradually apply hand pressure to the bulb and collect the filtrate in an appropriate vessel.
2.Pipet Mini Filter
This method is a quick alternative to suction filtration. This method is good for small quantities of solution when the solid is not desired. A disposable glass pipet is layered with glass wool and Celite (Figure 4-3). The filtration is facilitated by forcing the solution through the Celite and glass wool with a disposable pipet bulb. This filtration method is good for the preparation of NMR and IR solution samples.
C.Schlenk Filtration
The basic problem in Schlenk filtration is to minimize the exposure of the reaction mixture to moisture or oxygen. Normally there are three pieces of glassware involved in the operation. There are two variations, similar in concept but different in equipment, pictured in Figures 4-4 and 4-5. The trick is to connect the flask containing the reaction mixture to the Schlenk frit which is in turn is fastened to a large receiver Schlenk flask. In most cases where the desired product is the precipitate, it is wise to use a receiver flask whose volume is at least twice that of the reaction flask to allow for washing of the product. The Schlenk frit and receiver assembly should be evacuated and filled with inert gas at least three times before anything else is done.
Using equipment in Figure 4-4, there are essentially two ways of transferring the mixture into the frit. If the product is fine grain in nature, the mixture may simply be transferred via a cannula of suitable size by applying a partial vacuum to the collecting flask. (The cannula should be thoroughly purged with inert gas before connecting it to the reaction flask.) The more delicate way is to open one end of the reaction flask (the bent side) and with dexterity and quickness connect this to the mouth of the Schlenk frit under a positive flow of nitrogen. This is best done by greasing the bent side arm joint, removing septa from both the reaction flask and the Schlenk frit and quickly combining the two with a large nitrogen flow present. This latter method of joining the frit with the reaction flask involves a certain degree of mobility so care must be taken not to clamp things too tightly. When doing this the first time, it is wise to practice. The equipment in Figure 4-5 can be assembled anaerobically in the dry box, avoiding the "gymnastics" of Figure 4-4 assembly of reaction flask and frit. Washing of the product is simply achieved by using a cannula to transfer solvent from a reservoir flask or bottle onto the filtered product. Note: For other variants of glassware equipment and set-up consult the references in part A.
D.Kramer and Cannula Filtration
Air-sensitive samples and solutions may be conveniently filtered on the bench top using Kramer and Modified Kramer Filters with cannula techniques. Finely divided suspensions of impurities in air-sensitive solutions (such as those generated in Grignard reactions, sodium amalgam reductions, etc.) can be removed by using a disposable version of the Kramer filter. This filter, Figure 4-6, is comprised of a disposable syringe and needle, glass wool, and
Celite. The disposable syringe and needle is packed with a layer of glass wool, a layer of Celite and then another layer of glass wool. The syringe barrel is topped with a rubber septum. The filter is degassed by vacuum/inert gas charge cycles or by an inert gas purge. The solution to be filtered is transferred via cannula through the rubber septum, passed through the filter and collected in a receiving flask. The filter and its contents can then be discarded in an appropriate manner. (A commercially available Kramer filter is shown in Figure 4-7.)
If the solid is to be isolated the Kramer filter can be substituted by a glass frit. The top of the glass frit is capped with a rubber septum. The stem of the funnel is inserted into a predrilled hole of another septum which is in the receiving flask. The filter can be used as previously described for the Kramer filter.
E.Filtered Stick (Gas-Dispersion Tube)
This method consists of a dry, coarse gas-dispersion tube immersed in a liquid and connected to the receiving flask by flexible tubing (Figure 4-8).
The liquid is forced into the receiving flask by nitrogen pressure. If the liquid is the desired component the flexible tubing should be made of an inert material such as Teflon. An alternative, is to place a rubber septum on the end of the gas-dispersion tube and use a cannula to transfer the liquid.
This method has the advantage of allowing the solution being filtered to be heated or cooled during filtration. Disadvantages are that this method may be slower than others and that the small surface area of the gas-dispersion tube may clog easily.
F.Millipore Filtration
Millipore filters are thin, porous structures made of pure and biologically inert cellulose esters or related polymeric substances. They are available in more than 20 pore sizes ranging from 14 μm to 25 nm (0.025 μm); in disks from 13 to 293 mm in diameter. Their characteristics include very uniform pore size, high porosity and flow rate, high chemical stability (even toward concentrated acids and bases), negligible residue after incineration and transparency when pores are filled with an immersion oil of matching refractive index. Write for Catalog MC/1, Millipore Corporation, Ashby Road, Bedford, Mass. 01730. (See Scale 4-1 at end of this section.) Other membrane filters can be purchased through chemistry supply houses such as Matheson Scientific, Inc.
Due to their durability, Belman, Alpha Metrical Filters have been found to be extremely reliable and stand up to most organic solvents. These membranes are small diameter, small pore size syringe filters which limits their use to very small scale reactions or NMR/EPR sample preparation in which small particulate matter is removed from a 1-5 mL liquid sample. With the use of syringe/Schlenck techniques, this can be an anaerobic filtration (Figure 4-9).
V.Volumetric Gas Transfer
A.Vacuum Line Method
This method is used to introduce a large amount of gas into a reaction flask. For instance, to run a reaction under 50% CO and 50% N2.
With the hood line running, turn off N2 flow to Hg bubbler/manometer. Attach vacuum line stopcock No. 3 to stopcock No. 2 (Figure 5-1). Using a Y tube and vacuum tubing connect vacuum line stopcock No. 1 to the Schlenk flask and to the gas regulator of the CO tank. Open stopcock No. 1 to N2 side of vacuum line. Open stopcock No. 2 to vacuum. Slowly and carefully open stopcock No. 3 to N2 side of vacuum line. This will evacuate the system including the Schlenk flask and cause a column of Hg to be pulled up into the tube of the bubbler/manometer. This must be done slowly to prevent pulling Hg into the vacuum line. With our line you will probably be able to pull Hg up to the 5 cm mark (50 torr) on the meter stick. Close stopcock No. 2 and check that there are no leaks in the system by observing the height of the Hg column. Slowly open the CO gas regulator to introduce the desired pressure of CO. At the desired pressure, turn the CO gas regulator off. Close the stopcock to your Schlenk flask. Open stopcock No. 2 to vacuum to evacuate the system. Close stopcock No. 2 and turn on the N2 flow. When the system reaches 1 atm of N2 open the stopcock to the Schlenk flask to introduce N2. Close the stopcock to the Schlenk flask when the flask is full. Note: instead of bringing system pressure to 1 atm with N2, other gases (H2, SO2, etc) can be added in any quantity desired. Check the final concentration of the gas by G.C.
B.Gas Syringe Method
Fill a flask with the gas to be used by the vacuum line method (see 1 above) or by purging the flask with the gas until all traces of N2 and O2 are gone. Assuming that the gas is an ideal gas (22.4 L/mole) calculate the volume needed. Fill a syringe with the needed volume of gas and inject the gas into your reaction flask.
C.From Sealed Tubes (Isotope Studies)
Quantitative transfer of isotope labeled gases can be easily achieved by using a set-up shown in Figure 5-2. In this set-up, one needs to know the initial amount of gas (x mole) and the volumes V1 and V2 as defined in Figure 5-2. They can be measured by filling with water and weighing.(a) Notice V1 has three components: the upper part of S2, plastic tubing and the left part of S1. The length of the tubing can be varied to make V1 the desired volume.(b) The transfer is done in the following steps (reference to Figure 11):
1.Degas the solution of the reaction flask by the freeze-pump-thaw degassing technique.
2.Keep S2 closed and evacuate V1.
3.Close S1 and open S2 to allow gas to occupy both V1 and V2.
4.Close S2. Now the gas isolated in V1 is x.V1/(V1+V2) mole.
5.While keeping the reaction flask in liquid N2 and under partial vacuum, open S1 to let the gas condense into the reaction flask.
6.Close the stopcock of the reaction flask and keep a record on the quantity of gas left in the flask (V2) (= x.V2/(V1+V2) mole).
Now one has transferred x.V1/(V1+V2) mole of gas from the left flask to the reaction flask. By varying the length of the plastic tubing or adding a known volume flask between S1 and S2, one can easily adjust V1, thus controlling the amount of gas to be transferred.
D.Notes
(a).For V2 part, one can find a similar flask together with a stopcock and measure its volume. For a 100 ml flask manufactured by Aldrich, V2 is around 180 ml.
(b).For an 1/4" I.D. tubing, its volume per unit length is between 0.72 ml/in (thick wall) and 0.8 ml/in (thin wall).
VI.Bomb (High Pressure) Reactions
A.General Introduction
When either one of the reactants or the solvent is a gas at the temperature of the reaction it is necessary to carry out the reaction in a closed system. Depending upon the exact nature of the reaction, the temperatures and pressures to be used etc. one of the following types of reaction vessel will be employed: (a) a rocking, rotating, or stirred autoclave, (b) a sealed thick walled pyrex tube (Carius tube), (c) a champagne, CokeTM, or pressure bottle. Because high pressure reactions are always potentially hazardous, extreme caution should be exercised in utilizing the latter two techniques and they should never be used for reactions which are exothermic or are expected to generate gases or excessive pressures.
A considerable number of serious accidents have occurred by improper use of these techniques and the systems should always be treated with the utmost respect. In all cases you should adequately label all high pressure reactions to indicate the contents of the reaction vessel and any conceivable hazards.
B.Reactions Under Pressure (Sealed Tube Reactions)
For any reaction to be run on a large scale (more than 10-20 g total weight of reactants) or at maximum pressures in excess of 100 psi, only a suitable stainless steel housed high-pressure autoclave or bomb reactor should be employed. However, it is sometimes convenient to run small scale reactions at intermediate pressures in a small sealed glass tube or in a pressure bottle of the type used for catalytic hydrogenation on a Parr apparatus. For any such reaction the chemist should be fully prepared for the not uncommon possibility that the sealed vessel will burst. Every precaution should be taken to protect surrounding people and equipment from injury either from flying glass or from corrosive or toxic reactants. Centrifuge vials should be sealed with rubber stoppers clamped in their tops. Bottles should be wrapped with electrician's tape, surrounded with multiple layers of loose cloth toweling, and clamped behind a good safety shield. The sealed glass tubes may also be placed inside pieces of iron pipe threaded at each end and closed with pipe caps. The best source of heat for such vessels is steam since an explosion with electrical heaters could start a fire and an explosion in a liquid heating bath would distribute hot liquid around the area. Any reaction of this sort should always be labelled with signs to indicate the contents of the reaction vessel and the explosion hazard.
For reactions to be run in sealed tubes, similar precautions are followed. The tubes may be heated either with steam or in a specially constructed "sealed-tube" furnace which is heated electrically with a thermostatic control and is so located that the force from any exploding tubes is directed into a safe area.
For small tubes, ordinary pyrex glass tubing with an outside diameter of 5-8 mm may be used. Special thick-wall pyrex pressure tubing must be used for larger diameter reaction vessels. The initial reaction tube is constructed as in Figure 6-1A with care taken not to have thin spots in the bottom or in the
constricted section. The reactants are added to this tube such that the tube is never more than one-half full (heated liquids are essentially incompressible) with a pipet or syringe in such a way that no material is deposited on the constricted section of the tube. The tube is then swept with nitrogen (Figure 6-1B) and concurrently cooled in a Dry Ice bath (NOT a Dry
Ice-acetone bath). When the reactants are thoroughly chilled, the nitrogen line is removed and the constricted tube is immediately sealed with a small
oxygen-gas torch. The sealed tube (Figure 6-1C) is heated with steam or in a "sealed-tube" furnace following the precautions noted above.
When the required heating time is complete, the sealed tube or bottle is allowed to cool to room temperature. If a sealed-tube furnace is being used and the contents of this tube are non-flammable, one can heat the tip of the tube protruding from the furnace with a small oxygen-gas flame until the pressure in the tubes is released by breaking the molten glass. For sealed bottles and sealed tubes of flammable materials, the tubes, while protected from the operator with cloth toweling and a safety shield, are slowly cooled first in an ice bath and then in Dry Ice, after which the clamp and rubber stopper are removed from bottles and the tips of the sealed tubes are heated to the melting point to release any remaining internal pressure. After the pressure has been released, tubes are cut open by cracking along a file mark in the usual way.
C.Autoclave Reactions -- General Considerations
The Purdue Chemistry Department has autoclaves available for general use. They are located in specially designed rooms and can be scheduled for use through the instrument shop.
Autoclaves made of stainless steel are the preferred systems for high pressure work. Autoclaves and autoclave installations will vary from one laboratory to another but they all have one thing in common - a considerable amount of engineering know-how, and experience has gone into their design manufacture and assembly. Provided that they are not misused mechanically, the temperature and pressure specifications are not exceeded, they are not subjected to shock heating or cooling (which can cause stress and fatigue), and they are not severly chemically corroded, autoclaves should not be subject to failure. Moreover the removal of built-in safety devices such as rupture discs, or sealing an autoclave under pressure without monitoring it during the reaction or other kinds of operator negligence are likely to result in serious hazards. There is always the possibility of failures of various types and the possibility of an explosion from flammable gases or solvents above their boiling points, escape of toxic gases, etc. In order to minimize the hazards to the operators, autoclaves are isolated in steel plated cubicles which are individually vented; as far as possible the controls for monitoring temperature, pressure, etc. outside the cubicle such that they can be operated remotely without exposing the operator to a pressurized vessel at elevated temperatures. As a final note of caution, makeshift equipment is hazardous and on no account should either compressed gas or questionable high pressure equipment be added or substituted into an autoclave system. Before considering in detail the instructions for operating an autoclave system, some consideration of the hardware used to construct the auxiliary apparatus will be given. This is meant to be of an informative nature rather than to encourage the dismantling of the system.
There are only a few bomb reactors or autoclaves available to us. Figures 6-2A and 6-2B depict one such reactor and the valve system used to seal it. The specifications of these reactors should be familiar to you before you begin so that the apparatus does not become shrapnel during your reaction. Also, become familiar with the gas you are pressurizing, its phase transitions, its density (as a gas, liquid and solid at various temperatures) and its toxicity and flammability. The understanding of bomb volume and gas properties will allow you to know how much gas is needed to achieve a certain pressure in the bomb at room or elevated temperatures. The best method to determine how much gas you are placing into the bomb is by calibrating the tank regulator. Gas can be frozen into the bomb reactor at liquid N2 temperatures as a function of regulator equivalents. In the case of CO and CO2 reactions, for example, this proves to be an effective method.
The case of running a reaction in liquid CO2 is presented below to illustrate the essential principles. Figure 6-3 depicts CO2 phase transitions. The density of CO2(g) = 1.977 g/L (25°C). The density of CO2(l) at 25°C = 0.93 g/mL; at 30°C (critical temp) ♪ = 0.598 g/mL. The density of CO2(s) is ~1.6 g/mL. There are three solid phases of CO2 with different densities which are much more dense than the liquid. First, a lab CO2 regulator's "dead space" volume is calibrated by displacing liquid H20 from volumetric glassware with the volume of CO2(g, 1 atm, 25°C). Tank CO2 is typically 990 psi at 25°C. The regulator is charged with tank CO2 at 990 psi. The main tank valve is closed. The CO2 trapped in the "dead space" of the regulator is then expanded to 1 atm through the regulator needle valve to displace a measured volume of liquid. One CO2 regulator when filled with CO2 at 990 psi was calibrated to correspond to 1 liter CO2 at 1 atm. If one freezes 3 liters (or 3 regulators full) of CO2 into the 5 mL bomb reactor, this corresponds to 5.93 g of CO2 solid, which upon warming to room temperature will yield 6.38 mL of pressurized (~1700 psi) liquid at 25°C in a 5 mL bomb reactor. A glass lined, 5 mL bomb reactor in our lab is rated at over 20,000 psi and therefore will easily accommodate the 1700 psi of this type of reaction. Some reactors, however, may not. Also, if you wish to run at less or greater pressure you can regulate it by the quantity of initial CO2. To do other gas reactions one must know phases, densities, and PVT characteristics for those specific gases to ensure that you are running a safe reaction.
D.Low Pressure Reactors7,8
Two low pressure glass reactors, both constructed of commercially available parts, have been found to be very useful in organometallic synthesis and reactivity studies. The simplest design (Figure 6-4, right hand side) is a Fischer-Porter/Lab-Crest Scientific 3 oz. aerosol pressure vessel (with associated metal couplings, but lacking a cylindrical plastic shield for clarity) with a double-end shut-off quick connect fitting, adjustable pressure relief valve and septum inlet/sample withdrawal point backed up by a plug valve. This vessel can be loaded with an organometallic complex dissolved in a solvent by either glovebox or Schlenk line techniques (in the latter case by use of a female quick connect attached to a metal rubber tubing hose connector) and then connected to a quick connect equipped gas manifold containing a guage, a connection to the gas supply tank and an evacuation point (which is hooked up to a Schlenk line). The adjustable pressure relief valve is an important safety feature which is generally set to 75 psi; the unscratched bottles are presumably safe to 100 psi depending on internal volume (Lab Crest does not certify these vessels for any given pressure and should be operated routinely with safety shields around the gas manifold). For added safety, Lab Crest Scientific (manufacturer of Fischer-Porter equipment) also sells cylindrical plastic and stainless steel mesh shields for various size (3, 6, and 12 ounce) bottles. The plug valve backing up the septum inlet allows one to easily change the septum during kinetic studies by partial opening of the plug valve while screwing on the septum retaining nut. Construction of the apparatus from other materials (e.g., Monel) would allow use of the apparatus with more corrosive gases.
Figure 6-4 also depicts a pressure reactor with integral pressure- equalizing addition funnel (left hand figure, with pressure bottle and couplings removed). The addition funnel feature is extremely useful in low-pressure addition reactions (for example, in additions of alkali metal amalgams to organotransition metal species in the presence of gaseous reactants). Since common stainless steel alloys are inert to mercury, the entire apparatus was constructed from this material; the added cost is more than compensated for by its increased versatility. As with the simple reactor, this addition funnel equipped reactor allows one to withdraw samples during the course of a reaction. The three-way ball valve allows one to isolate the sample cylinder area from the reactor, fill it with a reagent solution using Schlenk procedures and then repressurize it prior to sample addition. A short piece of TeflonTM tubing is used, press fitted into the port connector located below the cylinder valve, to conduct the reagent solution into the glass vessel. The sample cylinder is available in a number of volumes; which can be accomodated easily by increasing the length of stainless steel tubing in the pressure equalizing branch.
Figure 6-5 shows a disassembled view of the simple reactor and the addition funnel reactor is shown in expanded view in Figure 6-6; in Figure 6-6, the Lab Crest couplings are omitted from the view for clarity. Figure 6-6 shows the location of the TeflonTM tubing and the port connector, located below the shut-off valve, into which the tubing is press-fitted. Tables 6-1 and 6-2 list the required parts; the simple reactor and addition funnel reactor in stainless steel cost $341 and $547, respectively (January 1987 prices), while the analogous prices in brass are $284 and $404. An appreciable portion of the cost is the 40% markup for the purchase of unit quantities of the Lab Crest equipment from Aerosol Laboratory Equipment; Lab Crest Scientific only sells in lots of one dozen. The pressure-equalizing addition funnel reactor can be constructed (in stainless steel, which is recommended) for $466 if the 3-way ball valve is omitted. One valuable, though expensive ($42), feature is the substitution of a size 210 KalrezTM O-ring for the needle valve adapter O-ring supplied by Lab Crest Scientific. Appreciable degradation of common O-rings with solvents such as tetrahydrofuran is noticed and requires frequent replacement, while KalrezTM is a fluoropolymer inert to all substances except molten alkali metals.
E.General References
(1)H. Adkins, "Reactions of Hydrogen" University of Wisconsin Press 1937, Chapter 3.
(2)W. L. Jolly, "Synthetic Inorganic Chemistry" Prentice Hall, 1960, Chapter 14.
(3)J. C. Hileman, "Preparative Inorganic Reactions" Volume 7, Editor W. L. Jolly Interscience 1964, Chapter 4.
(4)"The Matheson Gas Data Book" 1966 Matheson Co. Inc. Continual supplements are issued for this book and it is really indispensable for finding information on the handling, toxity, etc. of all commercially available gases. The library keeps an up to date version of this handbook on file.
(5)A. Weissberger, "Technique of Organic Chemistry" 2nd Ed. Volume II, Chapter 1 "Catalytic Reactions" and Volume III, part 2, Chapter 5 "Operations of Gases".
(6)"M.I.T. Laboratory Techniques Manual", Volume II, Chapter 29.
(7)Bain, M. J.; Lavallee, D. K. J. Chem. Educ. 1976, 53, 221.
(8)Messerle, L. J. Chem. Educ., submitted.