Air Sensitive Techniques 1:Using Schlenk Lines

Advanced Research Techniques Workshop

April 20th 2011James Watson

Outline

Why use air-sensitive techniques?• Common air-sensitive compounds

Equipment• Specialist glassware• The Schlenk line• Purge and refill• Cycling tubing

Handling Reagents• Dry solvents and distillation• Measuring and weighing• Spills/Fires

Clean-up• Reagents• Glassware• Syringe/cannula

Workshop 20/04/11

Why Use Air Sensitive Techniques?

• Many commonly used chemical reagents are extremely reactive

towards water and/or oxygen and will oxidise,

decompose, ignite or even explode

• Air sensitive techniques have been developed to avoid contact with

air and moisture from the

atmosphere at every step

!! these techniques do NOT protect from explosive or shock sensitive materials,

and provide limited protection from toxic compounds !!

Common Air Sensitive Compounds

• Examples of pyrophoric compounds:

- Metal alkyls and aryls e.g.

RMgX, RLi, RNa, R3Al, R2Zn

- Metal hydrides e.g.. NaH,

KH, LiAlH4

- Hydrides e.g.. B2H6, PH3,

AsH3

- Boranes, phosphines,

arsines

• Examples of chemicals which react violently with water

- Metal hydrides

- Metal amides

- Alkali metals e.g.. Na, K, Cs

- Many main group halides

e.g.. BCl3, BF3, AlCl3, PCl3, SiCl4

Specialist Equipment

• Glove Box – for solid reagents that must be handled under

completely dry conditions

• Glove Bags are also available cheaply for less sensitive compounds

(not suitable for pyrophoric materials)

Air Sensitive Techniques Apparatus

Ampoule/graduated ampoule

N2 inletsTipper funnel Cap

Schlenk flask Dropping funnel

Air Sensitive Techniques Apparatus

Filter stick Condenser

Cannula

Glass syringe and plunger

Frit

The Schlenk Line (or Double Manifold)

A

C

B

DE

F

G

H

The Schlenk Line (or Double Manifold)

1. Connect 2 taps with one piece of tubing, ensuring the nitrogen supply is off

2. Turn one of the taps to vacuum, then slowly open the other tap to N2 to pull the

mercury up the exhaust line, whilst the air is sucked from the manifold

3. Close the tap turned to the N2 manifold, and turn on the nitrogen supply to purge

4. Repeat steps 2 – 4, twice

• After assembly, the Schlenk line must be purged with nitrogen as

follows (only suitable for Schlenk

lines with 1m long bubbler and sufficient Hg in the reservoir):

A. Metre-long nitrogen bubbler

E. Two-way double oblique manifold taps

B. Nitrogen line

F.

Vacuum tubing

C. Tubing to nitrogen supply

G. Trap surrounded by liquid N2 dewar

D. Vacuum line

H.

Tubing to vacuum pump

The Schlenk Line (or Double Manifold)

check all taps on the manifold are closed

check all joints are streak-free

ensure the trap is empty and connected to the line with no streaks at the joint

check the nitrogen supply by turning on the tap until there is a good flow through

the mercury bubbler

• Before switching on the vacuum pump, do a visual check of the line:

Liquid Nitrogen

• Liquid nitrogen is a cryogenic fluid which is extremely cold and boils at -

196 oC

• Small volumes of liquid vaporise into large volumes of gas, ~700 times

expansion

!! wear safety goggles and protective clothing at all times !!

!! never draw air through traps containing liquid N2, as explosive liquid O2 can condense !!

Hazards

Cold burns can occur very rapidly and over a wide area – always wear

thermoprotective gloves (available from Gas Safety UK, product code 99-002,

£16)

!! do not wear cloth gloves of any kind !!

Asphyxiation can occur as liquid nitrogen rapidly expands to large volumes of

nitrogen gas.

!! never accompany a dewar containing liquid N2 in a lift !!

Over pressure will occur if the rapidly boiling liquid N2 is used

in a closed system. Beware of an “ice-dam” forming in apparatus.

!! never screw a lid on a thermos flask containing

liquid N2 !!

Pump Maintenance

• Oil Change: every 6 months or when necessary

1. open outlet valve and

decant oil into waste bottle/drum via funnel

2. pour fresh oil into the inlet

valve using a clean funnel to flush out old oil

3. close outlet valve and fill

pump• Measuring Pressure using a McLeod gauge

1. attach to the Schlenk line using

rubber tubing

2. turn the two-way double

oblique manifold tap to vacuum slowly

3. carefully rotate the gauge to

the vertical position to read the vacuum pressure

4. turn back to horizontal and

repeat step 3 until the reading is constant

ideal pressure should be 10-2 torr or lower

Pump Maintenance

!! ensure liquid N2 is always topped up around traps

to prevent volatiles contaminating pump oil !!

• Poor Vacuum: cannot achieve a good vacuum

1. check vacuum tubing for

degradation and replace if necessary

2. check oil level and for

discolouration – change if necessary

3. check joints and taps in line

and ensure there are no streaks in grease

4. if adequate vacuum cannot

be achieved, take the pump to the workshop

to be tested and cleaned

Purge-and-Refill: How to Cycle Tubing

• Cycling tubing and glassware using the purge-and-refill method

ensures all air is removed and replaced with inert gas

1. turn on the vacuum pump

and have liquid N2 around the solvent traps

2. turn on the nitrogen supply

and ensure the bubbler is at a gentle rate

3. connect glassware to a tap

on the line using thick-walled rubber tubing

4. cycle the tubing only (the

tap on the glassware remains closed):

a.

turn the two-way double oblique manifold taps to vacuum to purge

b.

after a few seconds, rotate the tap to refill with nitrogen (the

mercury/oil in the bubbler will be sucked up). If

there are already

other taps in use under nitrogen, close these

before turning new

taps to nitrogen, and only re-open

when the pressure is equalised

c.

wait for the pressure to equalise and the bubbler to begin bubbling

d.

repeat steps a – c twice more to purge-and-refill

5. with tubing under nitrogen, the

stopcock on the glassware can now be opened

6. when the bubbler begins to

bubble again, the pressure is equalised and the

flask and tubing are ready for further manipulation

n.b. if connecting more than one piece of

glassware and tubing to the line, the

above steps must be carried out simultaneously for each piece

Schlenk line tap

two-way double oblique manifold taps stopcock

Purge-and-Refill: How to Cycle Tubing

Positive Nitrogen Flow

• at all times during a reaction, the system

should be

under a slight positive pressure of nitrogen (positive

flow) which can be

visually indicated by the mercury or

oil bubbler

• when removing stoppers or caps from

apparatus, there must be a

positive flow of N2. This provides a protective

atmosphere “blanketing” the glassware from entry of air

and moisture

Glass-Aware

Plan ahead!

1. Plan the whole reaction ahead of time (a diagram for each step can be

helpful at first!)

how many Schlenk flasks will I need?

will I need a dropping funnel/condenser/frit?

2. Pre-heat all glassware in an oven (>100 oC, > 30mins), then assemble whilst hot using

silicone grease at the joints (see next slide), and allow to cool under

vacuum.

Open joints must be closed with stoppers or glass caps.

Schlenks may also be flamed under vacuum with great care using a Bunsen

burner or heat gun !!

never heat a sealed system !!

3. When cool, purge the glassware with nitrogen and cycle. Schlenk flasks can then be

weighed with their stoppers and stirrer bars.

Mark Schlenks and stoppers with corresponding symbols to avoid mix-up

Laboratory glassware contains a thin film of adsorbed moisture which must be removed

Greasing Joints

• when assembling glassware using grease there should be no streaks

in the grease at the joints. This ensures that the joints will not

seize and that no air can enter.

1. apply a small amount of

grease to the male joint and spread along the length

2. assemble the joint and rotate

carefully to distribute the grease. If streaking

occurs, add an additional small amount of grease to cover

this area

3. the joint is correctly greased if

no streaks appear

streaked joint streak-free joint

Dry Solvents

Distillation stills

apparatus and drying agents

Storage

molecular sieves

Transferring to reaction vessel

cannulae / syringes

• Dry solvents must always be used, as standard bench top solvents can

contain up to 30% water. These must be dried and handled

carefully.

Distillation Apparatus

1. Round bottom flasks (still pot)

2. Heating mantle

3. Condenser

4. Inert gas via bubbler

5. Solvent collector

6. Solvent outlet

7. Syringe port

8. Overflow

1

2

3

5

7

6

8

4

Solvent Drying agent

Diethyl ether* / petroleum ether*Distil over sodium pieces (0.5% w/v) and benzophenone (1 spatula per litre)

Dichloromethane Calcium hydride 5% w/v

Toluene* Distil over sodium pieces (1% w/v)

DMF* Distil over calcium hydride (1% w/v)

THF* Distil over potassium pieces (1% w/v)

Acetonitrile* Distil over calcium hydride (1% w/v)

* these solvents can be pre-dried over sodium.

Drying Agents

!! never add sodium to chlorinated solvents – an explosion may occur !!

Collecting and Storing Dry Solvent

• Once collected, dry solvent must be stored in a suitably dry manner.

This can be achieved by

using 4Å molecular sieves which have a cage-like crystalline structure

which captures water.• To activate molecular sieves:

1. Pre-heat molecular sieves in hot oven overnight. Leave ampoule in oven for at

least 1h !! Young's taps will be damaged if placed in the oven !!

2. Pour sieves into ampoule and insert Young’s tap (but do not close)and connect

to Schlenk line. Turn the Schlenk line tap to vacuum.

3. Place ampoule in a heating mantle, using a clamp stand. Turn heat dial to 7.

4. Heat for at least two hours. Turn off heat, and allow ampoule to cool under

vacuum

5. When cool, cycle ampoule, and leave under nitrogen until

ready to use

Collecting and Storing Dry Solvent

• Collecting solvent from distillation apparatus

1. turn on the heating mantle, water supply and check

N2 flow. If the collector has a tap close it.

2. when collector is full, turn off heating mantle and

allow solvent to cool

3. connect ampoule with sieves to an inert gas line

using PVC tubing; turn the gas on first

4. insert a needle through the tubing to purge air from

the Young's joint

5. remove Young's tap and place ampoule under

solvent outlet. Turn off N2 supply to prevent blow-

back.

6. collect solvent into the ampoule!! distillation apparatus can be dangerous,do not use without proper training !!

Transferring Dry Solvent from Ampoule to Schlenk

1. connect your solvent ampoule and dried Schlenk flask (see Glass-Aware) to the

Schlenk line and cycle tubing

2. unscrew (anticlockwise) Young's tap and remove. Maintain a positive pressure of N2,

creating an inert blanket over the solvent.

3. quickly and carefully insert the correct sized subaseal (usually no. 21) containing a

bleed needle (to purge the cavity with N2) into the neck of the ampoule4. open the stopcock of the Schlenk flask.

Maintain a positive pressure of N2 and

remove the stopper. Insert a subaseal

containing a bleed needle. Be sure to rotate

this bleed needle to purge the large cavity,

then remove the needle.

Transferring Dry Solvent

5. Insert one end of a cannula/double-tipped needle into the ampoule and check the

nitrogen is flowing through against your hand. Insert the other end into the Schlenk

flask.

6. Put a bleed needle through the subaseal of the Schlenk flask, and check nitrogen

flow against your hand. Close the Schlenk flask tap and lower the cannula/double-

tipped needle into the solvent to transfer. 6. The pressure of nitrogen will now force the solvent into

the empty Schlenk.

7. After transferring the desired amount, lift the cannula

out of the solvent in the ampoule.

8. Now open the tap to restore N2 flow, remove the bleed

needle and cannula. Clean cannula as described later

(Syringe/ Cannula/ Needle Clean Up slide)

Cannula

Dry Solid Reagents: from the bottle

powder funnels

Dry Solid Reagents: from a Schlenk flask

transfer of solids from Schlenk flask to Schlenk flask

Dry Liquid Reagents: from the bottle

cannulae/syringes

Measuring and Weighing Dry Reagents

• Dry reagents must be carefully measured or weighed to ensure that

their potential contact with air and moisture is

minimised.

Weighing Out: Dry Solid from a Bottle

1. prepare a dry, pre-weighed Schlenk flask (see Glass-Aware) and a dried powder

funnel (long-necked funnels are better to avoid compound sticking to

greasy joint!)

2. clamp the Schlenk flask and connect to the Schlenk line. Cycle the tubing.

3. while under a gentle flow of nitrogen, remove the stopper. Test the flow against

your hand (too strong a flow will blow your solid back out of the flask)

4. do not block the joint completely with funnel (solid will blow out), hold it just

above or use a ring clamp

5. add solid to flask. Remove any solid sticking to the grease with a tissue and re-

grease stopper. Ensure all solid is removed, it can cause the joint to crack.

6. replace the stopper and weigh the flask.

1. Prepare a dry pre-weighed Schlenk flask (see Glass-Aware), and a tipper funnel capped

on one end, with an N2 inlet tap at the other end.

2. Clamp all glassware and connect your pre-weighed Schlenk, your reagent Schlenk, and

the tipper funnel to the Schlenk line. Cycle tubing simultaneously.

4. Close the N2 inlet tap on the tipper funnel and remove

this, along with the stopper from the reagent Schlenk,

and connect the funnel to the Schlenk flask. Rotate

joint to remove streaks.

Solids likely to decompose over time may be better stored in a dried Schlenk under N2

3. Under a positive flow of nitrogen,

remove the stopper from your

pre-weighed flask and the cap from the tipper

funnel, and connect the two. Rotate the flask to ensure a

streak-free joint.

Weighing Out: Dry Solid from Schlenk flask to Schlenk flask

Weighing Out: Dry Solid from Schlenk flask to Schlenk flask

5. Secure the joints in place with elastic banding so

they stay together while tipping.

6. Close the tap of your reagent Schlenk flask, and

carefully turn your pre-weighed flask to vacuum

(if there is a stirrer bar in your pre-weighed flask,

use a magnet on the outside of the flask to

secure it)

7. Carefully tip an estimated amount of solid into

the pre-weighed Schlenk.

8. Clamp the reagent Schlenk flask. Carefully turn

the tap of the pre-weighed Schlenk back to N2.

Open the tap of the reagent Schlenk flask to

restore the flow of N2.

9. Under positive nitrogen pressure, remove the pre-weighed flask

and replace the stopper. Also replace the cap on the

tipper funnel and turn this flask back to

vacuum.

10. Now re-weigh your prepared Schlenk and calculate how much solid

was transferred.

11. If there was too much or too little, connect to the Schlenk line

again and cycle the tubing. Turn the reagent flask and

tipper back to nitrogen, and repeat from step 4.

12. When you are happy with the mass of solid transferred, remove

the tipper under positive nitrogen pressure and place stoppers

in both flasks.

Weighing Out: Dry Solid from Schlenk flask to Schlenk flask

Syringe transfer tips:

• Small quantities (up to 20 mL) of air-sensitive reagents and dry solvents may be

transferred with a syringe equipped with a thin, 12-18inch long needle. This avoids

having to tip reagent bottles and storage flasks. Tipping often causes the liquid to

come in contact with the septum/subaseal causing swelling, deterioration and spills

Using syringes:

1. Pressurise the vessel with N2 (for bottles see next slide). Subaseals can be inserted

into Schlenks/ampoules (as described in transferring solvents).

2. Purge the syringe with N2 by inserting into the septum/subaseal and filling with N2

only; the N2 pressure should push the plunger back, so that the syringe fills, and

then remove from the bottle and push N2 out into fume hood.

3. Repeat step 2 twice more

Measuring Dry Liquid Reagents: Syringes

Sure/Seal bottles

• Sure/Seal bottles have a crown cap and liner crimped in place

which gives some protection against air and moisture from the

atmosphere. Needles and cannulae can be inserted through

this seal.

1. Pressurise the bottle with N2 by inserting a needle connected to

a Schlenk line via a Luer adapter (check the N2 flow first)

2. The reagent can then be dispensed using a syringe or double-

tipped needle inserted through the hole in the metal cap.

1. Liquids likely to decompose over time may be better transferred

to a dried ampoule under nitrogen for storage.

Measuring Dry Liquid Reagents

Crown cap with hole

Luer adapter

Measuring Large Volumes of Dry Liquid Reagents

• When measuring large volumes of liquid, it is not advisable to use a syringe. Instead

use a graduated ampoule and a cannula.

1. Connect a dry graduated ampoule and your reagent flask or bottle to the Schlenk line.

Cycle tubing simultaneously.

2. Have ampoules and Schlenks under N2, and replace stoppers/ Young's taps with

subaseals. Reagent bottles can be pressurised with N2 as described on the previous

slide.

3. Transfer liquid from a reagent bottle/ampoule to the graduate ampoule using an oven

dried cannula/double-tipped needle, as described in Transferring Dry Solvents. When

you have the desired amount, return nitrogen flow and remove the bleed needle

4. Then transfer the liquid reagent from the graduated ampoule to reaction vessel, using

the cannula/double-tipped needle, and opening/closing the stopcock to alter the

nitrogen flow and adjust rate of addition.

• Some reactions can be monitored by 31P and 11B

NMR spectroscopy, by preparing an NMR

sample in an NMR tube holder, as shown.

• The NMR tube is placed in the holder and dried

in the same fashion as a Schlenk flask.

• Transfer a sample of the reaction solution in

the same fashion as transferring solvent.

NMR tube holder

Connecting condensers and dropping funnels

1. Dry glassware and assemble as described in Glass-Aware.

Cap the bottom joint of the glassware with a greased cap

and insert a greased N2 inlet into the top joint, ensuring

there are no streaks.

2. Connect the N2 inlet to the Schlenk line using PVC tubing,

and turn the two-way manifold tap vacuum. Allow to cool

under vacuum.

3. Elastic band the cap and inlet, and cycle the glassware.

4. Attach reaction vessel to Schlenk line and cycle tubing.

5. Under positive N2 flow, remove stopper from flask and the

cap from the apparatus, and connect the two

Attaching Glass Apparatus

Connecting a frit and filtering solutions

1. Dry glassware and assemble as described in Glass-Aware. Cap both joints of the

glassware with greased caps and insert a greased tap into the stopcock, ensuring

there are no streaks.

2. Connect the N2 inlet to the Schlenk line using PVC tubing, and turn the two-way

manifold tap vacuum. Allow to cool under vacuum.

3. Elastic band the caps and cycle the glassware.

4. Attach reaction vessel to Schlenk line and cycle tubing.

5. Under positive N2 flow, remove stopper from flask and bottom cap from the frit, and

connect the two.

6. Transfer reaction solution by removing the top cap and inserting a subaseal

containing a bleed needle. Transfer using cannula techniques as described in

Transferring Dry Solvents

Attaching Glass Apparatus

Solvent must be removed on the high-vac line using an external trap

Removing Solvent

1. Connect external trap to the Schlenk line by the top outlet.

Connect the external trap to the Schlenk flask with a piece of

tubing from the side-arm. The Schlenk flask must be closed.

2. Place a Dewar flask around trap and fill with liquid N2.

3. Turn the Schlenk line to vacuum, and agitate the solution with a

stirrer bar or swirling. Slowly open the Schlenk stopcock. Solvent

will begin to bubble/bump

4. When the bumping subsides the tap can be fully opened.

5. The flask will become cold and solvent may freeze, warm very

gently heating with a heat gun.7. When all solvent is removed close the Schlenk stopcock, and close the Schlenk manifold

tap. Remove the tubing and take the trap out of the Dewar. Connect the flask to the line,

and cycle the tubing. Open the flask to N2.

Elastic bands are required to secure joints during flushing, as

the nitrogen pressure may open the seals of unsecured joints.

• Rubber bands are more secure than clips which are quite

flexible. Stoppers could easily come out of their joints if

there is a build up of vapour pressure inside the Schlenk,

exposing your material to the atmosphere.

• Schenk flask taps can also be secured with an elastic band.

Open: during a reaction to prevent accidental

removal

Closed: Schlenk can be left in a basket with tap secured

and cannot be knocked out

of position

Elastic Banding

Spills / Fires

Spills

• Phosphines/ mercaptans must be cleaned using bleach

• Lithium aluminium hydride can be wiped up using barrel roll, and can be quenched

by immediately and quickly submerging tissue in a sink full of water

• Sodium hydride can be destroyed with alcohol

Fires

• Always alert someone else first!

• Small fires can often be allowed to burn out

• In case of larger fires, use a dry powder extinguisher or fire blanket

• Empty Sure/Seal bottles – remove the crown cap and leave in the fume hood to allow

the last traces of reagent to hydrolyse or oxidise

• Destroy phosphines/mercaptans with bromine solution (IMS:bromine 100:1 approx.)/

bleach, followed with IMS, water and acetone (in that order).

• Destroy organometallic compounds with IPA/IMS followed by water, then acetone

• Alkali metals must be placed in a beaker filled with toluene, and destroyed using a

isopropanol:toluene solution (1:4). When doing this on a large scale (i.e. Still pot) do

this under an inert atmosphere.

Reagent Clean Up

Glassware Clean-Up

!! always use thick nitrile gloves or marigolds !!

!! never put greasy glassware in the oven !!

1. Disassemble glassware

2. Destroy phosphines, mercaptans and organolithiums as described on the

previous slide.

3. Dispose of reagents as appropriate and rinse the glassware with water

4. Wipe all grease from joints, stoppers, taps, caps etc.

5. Place glassware in a base bath (KOH in IMS) ensuring there are no air bubbles and

the glassware is completely submerged, for a minimum of 4 hrs; 16hrs max

6. Rinse glassware with water and place in an acid bath (HCl in water) for 1 hr min.

7. Rinse glassware with water then acetone and put back in oven

Syringe/ Cannula/ Needle Clean Up

• Clean all syringes and needles immediately after use (hydrolysis and oxidation

of reagents can cause needles to plug)

• Syringes rinsed at the sink , using the plunger to clean the needle. To rinse a

cannula/double tipped needle, use a Buchner funnel as shown with the

Subaseal clamped into place. Apply vacuum to pull solvent through cannula.

Order of rinse:

Bromine solution (phosphines); IMS; Water; Acetone

Dilute acid can be used to unblock a needle

Dry plunger and syringe separately in the oven

• Organolithiums must be destroyed using IMS

• Phosphines/mercaptans must be rinsed with IMS into bromine solution

(IMS:bromine roughly 100:1)

Summary

• Using air- and moisture- sensitive techniques is a necessary requirement for handling many types of reagents

• Dry glassware is essential

• When removing stoppers/caps from Schlenk flasks and other apparatus ensure that the inlet taps are open to nitrogen/inert gas flow

• Solid reagents can be stored in Schlenk flasks for prolonged use

• Remember to label all flasks and co-ordinating stoppers

• Sure/seals found on reagent bottle gradually degrade. Store liquid reagents in ampoules for prolonged use

Workshop 20th April 2011

1. Weigh zirconocene dichloride (0.5g) into a sample vial on the balance and

transfer to a separate Schlenk flask using a powder funnel.

2. Add dry THF (15mL) to the zirconocene using a syringe, then cool to -78oC.

3. Weigh out dry potassium tbutoxide from a Schlenk flask via tipper funnel into a

pre-dried, pre-weighed Schlenk flask. Weigh out approx. 0.5g

4. Add dry toluene from an ampoule using a syringe. Use 15mL.

5. Add dry nbutyl lithium from an ampoule using a syringe. Use 2.8mL of 1.6M

solution.

6. Now transfer the benzyl potassium into the zirconcene solution using a

cannula.

7. Concentrate the solution to around 1/3 of the volume and filter through a frit.

References

• Sigma-Aldrich Technical Bulletin AL-134

• Advanced Practical Organic Techniques. J. Leonard, B. Lygo, G. Procter

• http://www.safety.ncl.ac.uk/uploads/Handling%20of%20Liquid%20Nitrogen.pdf

• Advanced Practical Inorganic and Metalorganic Chemistry. R.J. Errington

Acknowledgements

Dr K. Izod

Mr J. Dyson

Miss L. Cotterill

The Postgraduate Committee

Other Workshops in the Series

Workshop Date

Using Mestre-Nova and Delta to analyse NMR data 23rd March 2011

Air Sensitive Techniques 1: Using Schlenk Lines 20th April 2011

Effective Quenching and Working-up of Reactions 18th May 2011

Recrystallisation and Growing Samples for X-Ray 15th June 2011

Industry Techniques 1: Flash Chromatography 13th July 2011

Air Sensitive Techniques 2: Using a Glove box 10th August 2011

Industry Techniques 2: Microwave Reactions 7th September 2011

• Sign-up sheet for each workshop will be available on the Postgraduate Notice board two weeks in advance

Dates, locations and titles to be confirmed

• PhD students: record attendance at each workshop in your e-portfolio 1 school PGRDP credit is available per workshop