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`weSAUNDERSGOLDENSUNBURSTSERIES
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`Bellingham,Washington
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`WesternWashingtonUniversity
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`DONALDL.PAVIA
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`GARYM.LAMPMAN
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`GEORGES.KRIZ,Jr.
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`introductionto
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`‘acontemporaryapproach
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`Secondedition
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`VisLOU
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`FABORATIOR
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`ORGANIG
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`Page 1 of 9
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`EISAI EXHIBIT 1059
`Eisai v. Crystal Pharm.
`PGR2021-00047
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`Page 1 of 9
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`EISAI EXHIBIT 1059
`Eisai v. Crystal Pharm.
`PGR2021-00047
`
`
`

`

`Address orders to:
`383 Madison Avenue
`New York , N Y 100 17
`
`Address editorial correspo11de11ce to:
`West Washington Square
`Philadelphia. PA 19 !05
`
`This book was se t in Times Ro man and Helvetica by Yo rk Graphic Services.
`The editors were John Vondeling. Carol Fie ld. Don Reisman. and Janet Wright.
`The art & design d irector was Richard L. Moo re.
`The text design was done by Phoenix Studio.
`The cover design was done at W. 8. Saunders.
`The production ma nager was To m O'Connor.
`This book was printed by W. 8 . Saunders Company.
`
`INTRODUCTION TO O RGAN IC LABORATORY TEC H N IQUES
`
`ISBN 0-03-058424-8
`
`© 1982 by C BS College Publishing. Copyright 1976 by W. 8. Saunders Company.
`All rights reserved . Printed in the
`United States of America.
`Library of Congress catalog card number 81-52762.
`
`234 026 9876543
`
`CBS COLLEGE PUBLISHING
`Saunders College Publishing
`Holt. Rinehan and W inston
`The Dryd en Press
`
`Page 2 of 9
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`

`

`Technique 2
`FILTRATION
`
`Filtration is a technique used for two main purposes. The first is to remove
`solid impurities from a liquid or a solution. The second is to collect a solid
`product from the solution from which it was precipitated or crystallized. Two
`different kinds of filtration are in general use: gravity filtration and vacuum ( or
`suction) filtration.
`·
`
`2.1 GRAVITY FILTRATION
`
`The most familiar filtration technique is probably filtration of a solution
`through a paper filter held in a funnel, allowing gravity to draw the liquid
`through the paper. In general, it is best to use a short-stemmed or a wide(cid:173)
`stemmed funnel. In these types of funnels there is less likelihood that the stem
`of the funnel will become clogged by solid material accumulated in the stem.
`This clogging is a particular problem if a hot solution saturated with a dissolved
`solid is being filtered. If the hot saturated solution coines in contact with a
`relatively cold funnel ( or a cold flask, for that matter), the solution becomes
`cooled. The rapidly cooled solution will be supersaturated, and crystallization
`will begin. Crystals will form in the filter, and either they will fail to pass
`through the filter paper or they will clog the stem of the funnel.
`Four other measures are feasible for preventing clogging of the filter. The
`first is to keep the solution to be filtered at or near its boiling point at all times.
`The second measure is to preheat the funnel , by pouring hot solvent through it
`before the actual filtration. This keeps the cold glass from causing instantane(cid:173)
`ous crystallization. The third way is to keep the filtrate (filtered solution) in the
`receiver hot enough to continue boiling slightly (by setting it on a steam bath,
`for example). The refluxing solvent heats the receiving flask and the funnel
`stem and washes them clean of solids. This boiling of the filtrate also keeps the
`liquid in the funnel warm. And fourth, it is useful to accelerate filtration by
`using fluted filter paper, as described below. A gravity filtration is shown in
`Figure 2-1.
`
`A. FIiter Cones
`
`The simplest way to prepare filter paper for gravity filtration is to prepare a
`filter cone, as outlined in Figure 2- 2. The filter cone is particularly useful when
`the solid material being filtered from a mixture is to be collected and used later.
`The filter cone, because of its smooth sides, can easily be scraped free of col(cid:173)
`lected solids. Because of the many folds, fluted filter paper, described in the
`next section, cannot be scraped easily.
`With filtrations using a simple filter cone, solvent may form seals between
`the filter and the funnel, and between the funnel and the lip of the flask. When
`a seal forms, the filtration stops, because the displaced air has no possibility of
`escaping. To avoid the solvent seal, you can insert a small piece of paper or a
`474
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`Page 3 of 9
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`FILTRATION
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`475
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`paper clip or other bent wire between the funnel and the lip of the flask to let
`the displaced air escape. Alternatively, you can support the funnel by a ring
`clamp fixed above the flask, rather than by placing it in the neck of the flask.
`
`FIGURE 2-1 . Gravity filtration
`
`B. Fluted FIiters
`
`The technique for folding a fluted filter paper is shown in Figure 2-3. The
`fluted filter increases the speed of filtration in two ways. First, it increases the
`surface area of the filter paper through which the solvent seeps; second, it
`allows air to enter the flask along its sides to permit rapid pressure equalization.
`If pressure builds up in the flask from hot vapors, filtering slows down. This
`problem is especially pronounced with filter cones. The fluted filter tends to
`reduce this problem considerably, but it may be a good idea to use a piece of
`paper, paper clip, or wire between the funnel and the lip of the flask as an
`added precaution against solvent seals. Fluted filters are used when the desired
`material is expected to remain in solution. These filters are used to remove
`undesired solid materials, such as dirt particles, activated charcoal, and undis(cid:173)
`solved impure crystals.
`
`2.2 FILTER PAPER
`
`Many kinds and grades of filter paper are available. Paper is generally
`available in fine, medium, and coarse porosities. Fine-porosity paper will catch
`very fine solid particles but generally gives very slow filtration. Coarse paper
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`Page 4 of 9
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`476
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`TECHNIQUE 2
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`FIGURE 2-2. Folding a filter cone
`increases the rate of filtration but may not catch all the particles. The paper
`must be correct for a given application. In choosing, one should be aware of the
`various properties of filter paper. Porosity is a measure of the size of the parti(cid:173)
`cles the paper allows through. Highly porous paper does not remove small
`particles from solution; paper with low porosity removes very small particles.
`Retentivity is a property that is the opposite of porosity. Paper with low
`retentivity does not remove small particles from the filtrate. The speed of filter
`paper is a measure of the time it takes a liquid to drain through the filter. Fast
`paper allows the liquid to drain quickly; with slow paper, it takes much longer
`to complete the filtration. Since all these properties are related, fast filter paper
`usually has a low retentivity and high porosity, and slow filter paper usually has
`high retentivity and low porosity.
`Table 2-1 compares some commonly available qualitative filter paper
`types and ranks them according to porosity, retentivity, and speed. Eaton(cid:173)
`Dikeman (E&D), Schleicher and Schuell (S&S), and Whatman are the most
`common brands of filter paper. The numbers in the table refer to the grades of
`paper as used by each company.
`
`2.3 VACUUM FILTRATION
`
`Vacuum, or suction, filtration is more rapid than gravity filtration, but
`without specially prepared filter media it does not catch fine particles without
`clogging the paper pores. In this technique, a receiver flask with a sidearm, a
`filter flask, is used. The sidearm is connected by heavy-walled rubber tubing to
`a source of vacuum. Thin-walled tubing will collapse under vacuum, due to
`atmospheric pressure on its outside walls, and will seal the vacuum source from
`the flask. A Buchner funnel (see Figure 2-4) is sealed to the filter flask by a
`rubber stopper or a rubber gasket (Neoprene adapter) cone. The flat bottom of
`the Bilchner funnel is covered with an unfolded piece of circular filter paper,
`which is held in place by suction. To keep the unfiltered mixture from passing
`around the edges of the filter paper and contaminating the filtrate in the flask
`below, it is advisable to moisten the paper with a small amount of solvent
`before beginning the filtration. The moistened filter paper adheres more
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`Page 5 of 9
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`FILTRATION
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`477
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`2
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`4
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`5
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`6
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`7
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`8
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`10
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`FIGURE 2-3. Folding a fluted filter paper, or Origami at work in the organic lab
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`Page 6 of 9
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`478
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`TECHNIQUE 2
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`TABLE 2-1. SOIi(cid:127) COMMON QUAUTATIY(cid:127) FILTER PAPER TYPaS
`AND APPROXIMATE RIELATIYE SP(cid:127) EDS AND RETENTIYITl(cid:127) S
`Fine
`High Slow
`
`z,,,
`"iii
`....
`0
`0
`a.
`
`i::'
`:~
`'E
`a>
`a:
`
`Q)
`
`"C
`Q)
`Q)
`a.
`Cl)
`
`Coarse Low
`
`Fast
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`SPEED
`
`Very slow
`Slow
`Medium
`Fast
`Very fast
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`E&D
`
`610
`613
`615
`617
`
`TYPE (by number)
`S&S
`576
`602
`597
`595
`604
`
`Whatman
`
`5
`3
`2
`1
`4
`
`strongly to the bottom of the Buchner funnel. Since the filter flask is attached to
`a source of vacuum, a solution poured into the Buchner funnel is literally
`"sucked" rapidly through the filter paper. To prevent the escape of solid materi(cid:173)
`als from the Buchner funnel, one must be certain that the filter paper fits the
`Buchner funnel exactly. The paper must be neither too big nor too small. It
`must cover all the holes in the bottom of the funnel but not extend up the sides
`of the funnel.
`Two types off unnel are useful for vacuum filtration. The Buchner funnel,
`which has already been considered, is used for filtering a large amount of
`crystals from solution. The Hirsch funnel, which is also shown in Figure 2- 4,
`operates on the same principle as the Buchner funnel, except that it is smaller
`and its sides are sloped rather than vertical. The Hirsch funnel is used for
`isolating smaller quantities of solid materials from a solution (smaller sizes of
`the Buchner funnel are also available for this purpose). In the Hirsch funnel
`also, the filter paper must cover all the holes in the bottom but must not extend
`up the sides.
`
`2.4 FILTER AID
`
`It was mentioned that specially prepared filter beds are needed to separate
`fine particles when using vacuum filtration. Often, fine particles either pass
`right through a paper filter or they clog it so completely that the filtering stops.
`This is avoided by using a substance called Filter Aid, or Celite. This material is
`also called diatomaceous earth, because of its source. It is a finely divided inert
`material derived from the microscopic shells of dead diatoms (a type of phyto(cid:173)
`plankton that grows in the sea).
`
`WARNING: LUNG IRRITANT
`When using FIiter Aid, take caw
`not to breathe the dust.
`
`Filter Aid will not clog the fiber pores of filter paper. It is slurried, or mixed
`with a solvent to form a rather thin paste, and filtered through a Bilchner funnel
`(with filter paper in place) until a layer of diatoms about 3 mm thick is formed
`on top of the filter paper. The solvent in which the diatoms were slurried is
`poured from the filter flask, and if necessary, the filter flask is cleaned before the
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`Page 7 of 9
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`FILTRATION
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`479
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`pressure tubing
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`Hirsch funnel
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`FIGURE 2-4. Vacuum filtration
`filtration is begun. Finely divided particles can now be suction-filtered through
`this layer and will be caught in the Filter Aid. This technique is used for
`removing impurities and not for collecting a product. The filtrate (filtered solu(cid:173)
`tion) is the desired material in this procedure. If the material caught in the filter
`was the desired material, one would have to try to separate the product from all
`those diatoms! Filtration with Filter Aid is not appropriate when the desired
`substance is likely to precipitate or crystallize from solution.
`2.5 TH(cid:127) ASPIRATOR
`
`The most common source of vacuum (approximately 10-20 mmHg) in the
`laboratory is the water aspirator, or "water pump," illustrated in Figure 2-5.
`This device passes water rapidly past a small hole to which a sidearm is at(cid:173)
`tached. The Bernoulli effect causes a reduced pressure along the side of
`the rapidly moving water stream, and creates a partial vacuum in the
`sidearm.
`A water aspirator can never lower the pressure beyond the vapor pressure
`of the water used to create the vacuum. Hence, there is a lower limit to the
`pressure (on cold days) of 9-10 mmHg. A water aspirator does not provide as
`high a vacuum in the summer as in the winter, due to this water-temperature
`effect.
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`Page 8 of 9
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`· 480
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`TECHNIQUE 2
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`FIGURE 2-5. Aspirator
`
`A trap must be used with an aspirator. A trap is illustrated in Figure 2-4. If
`the water pressure in the laboratory line drops suddenly, the pressure in the
`filter flask may suddenly become lower than the pressure in the water aspirator.
`This would cause water to be drawn from the aspirator stream into the filter
`flask and would contaminate the filtrate. The trap stops this reverse flow. A
`similar flow will occur if the water flow at the aspirator is stopped before
`the tubing connected to the aspirator sidearm is disconnected. ALWAYS
`DISCONNECT THE TUBING BEFORE STOPPING THE ASPIRATOR.
`If a "back-up" begins, disconnect the tubing as rapidly as possible before the
`trap fills with water. Some workers like to fit a stopcock into the stopper on top
`of the trap. A three-hole stopper is required for this purpose. With a stopcock in
`the trap, the system can be vented before the aspirator is shut off. If the system
`is vented before the water i~ shut off, water cannot back up into the trap.
`Aspirators do not work well if too many people use the water line at the
`same time, since the water pressure is lowered. Also, the sinks at the ends of the
`lab benches or the lines that carry away the water flow may have a limited
`capacity for draining the resultant water flow from many aspirators. Care must
`be taken to avoid floods.
`
`2.6 CRUDE FILTRATIONS
`
`Often one wants to make a very rapid filtration to remove dirt or impurities
`oflarge particle size from a solution. This is accomplished most easily by laying
`a loose mat of glass wool in the bottom of an ordinary funnel and pouring the
`solution through the mat. It may be helpful to decant, or pour off, the clear
`liquid gently before performing this crude filtration on the solid residue at the
`bottom of the flask.
`Small amounts of solution can be filtered in a like manner. A plug of glass
`wool is packed loosely into an eyedropper pipet, and the solution is dropped
`into the packed pipet by a second pipet.
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`Page 9 of 9
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