FEATURE

Hazards associated withlaboratory scale hydrogenations

Tilak ChEnvironm(Chemicconsin-MMall, MStates (Te-mail: t

Jeffrey Pthe Env(Chemicconsin-MMall, MStates.

16 �A

We report hazards associated with laboratory scale hydrogenations and the best practices for handlingcatalyst and hydrogen with three case studies. Fire, runaway reactions and explosions are commonlyassociated with hydrogenations due to the involvement of pyrophoric catalysts, hydrogen, flammablesolvents and pressure. Laboratory hydrogenation methods as well as procedures to minimize hazardsassociated with catalyst and hydrogen are presented.

By Tilak Chandra,Jeffrey P. Zebrowski

INTRODUCTION

Catalytic hydrogenations are extremelyuseful for chemical transformationson small and large industrial scales.Various functional groups (C O,NO2, C C, etc.) are reduced usinghydrogen over suitable catalysts suchas Pd, Pt, Rh, Ni, and Ru at ambientand/or elevated pressure.1–6 The natureof the catalyst, purity of substrates,temperature, pressure, contaminantsin the substrate, instability ofintermediates, and solvents affecthydrogenation processes. The majorsafety concern for any hydrogenationreaction is fire and explosion due tothe pyrophoric7,8a,b nature of thecatalyst, reagent, substrate, intermedi-ate instability, and use of the flamma-ble solvents, hydrogen and pressure(Figure 1). The primary hazard associ-ated with any form of hydrogen is

andra is affiliated with theent Health and Safety

al Safety), University of Wis-adison, 30 East Campusadison, WI 53715, Unitedel.: +608 609 0255;chandra@fpm.wisc.edu).

. Zebrowski is affiliated withironment Health and Safetyal Safety), University of Wis-adison, 30 East Campusadison, WI 53715, United

2015 Division of Chemical Health and Safety

ll rights reserved.

inadvertently producing a flammablemixture, leading to a fire or detonationwhen exposed to air, oxygen, orsparks. Thus applying a systematic ap-proach of risk analysis is critical forsmall as well as large-scale laboratoryhydrogenations.

Catalytic hydrogenation of nitrocompounds (Figure 2) is an economi-cal route2,9–12 for generating pharma-ceutical intermediates at laboratoryand industrial scales. Such reductionsvia hydrogenation are a well-definedclass of reactions with high hazardpotential.13 Substrate impurities, thewrong choice of catalyst, contaminat-ed hydrogen (carbon dioxide, carbonmonoxide and hydrocarbons) and lowconcentration of catalyst are majorcontributing factors for the runawayreactions during hydrogenation ofthe nitro groups.

The reduction of nitro compoundsrequires higher temperatures and useof alcoholic/flammable solvents. Eval-uation of operating procedures for theapparatus and a thorough inspectionof reaction vessels are critical beforemanipulating any high pressure exper-iment.

A proper hazardassessment suchasaliterature search about substrate/inter-mediate reactivity, catalysts and solventeffects should be conducted for pre-venting runaway reactions associatedto large scale and high pressure hydro-genations. Large scale reaction successalso depends on the hands on experi-ence of researchers. Standard operatingprocedures (SOPs) developed by a sub-ject matter expert for the hydrogena-tions should be used for trainingnew students and researchers. Proper

of the American Chemical Society. Published by Elsevier Inc

handling of catalysts is critical due tohigh reactivity before and after intro-ducing hydrogen. Existence of any im-purity or colored impurity in substratecan inhibit the catalyst activity resultingin partial reduction of the substrate andoccasionally in a run-away reaction.Substrates should be completely puri-fied prior to subjecting them to hydro-genations. Hydrogenation reactions arelargely exothermic in nature and caneventually increase overall pressure in-side the vessel.

LABORATORY HYDROGENATIONSAND HAZARDS

The primary hazard associated withany form of hydrogen is inadvertentlyproducing a flammable mixture, lead-ing to a fire or detonation (Figure 1).Use of hydrogen, pyrophoric catalyst,flammable solvents and generation ofin situ unstable intermediates are themain safety concerns during laborato-ry hydrogenations. Laboratory scalehydrogenations are mostly carriedout using a round bottom flask(ambient pressure), balloon method,suitable pressure vessels, shakers14,15

(Figure 3), or using a continuous-flowhydrogenation (H-cube). Understand-ing properties of hydrogen, catalysts,their manipulations and hands-on ex-perience16,17 is critical for a successfulhydrogenation at both small and largescales. Polar solvents (water) and lowflammable solvents are preferred overnon-polar and flammable solvents toprevent flash fires during catalyst ad-dition and during spent catalyst isola-tion. If used properly, water generally

. 1871-5532

http://dx.doi.org/10.1016/j.jchas.2015.10.019

[(Figure_2)TD$FIG]

Figure 2. Formation of unstable intermediates during catalytic hydrogenations ofnitro compounds.

[(Figure_1)TD$FIG]

Figure 1. Hydrogenation hazards.

[(Figure_3)TD$FIG]

Figure 3. Ambient pressure hydrogenation of thymidine.

keeps the catalyst wet during transferand filtration. For any hydrogenationreaction, flask and other glasswareshould be crack free, intact and freeof contamination. A properly function-al chemical fume hood or designatedarea for hydrogenation should be usedto avoid the accumulation of hydrogeninside the lab. Use of open heatingsystems, such as oil baths and heatingmantles should be circumvented toprevent flash fires. Uses of a waterbath, sand bath or heating blocks aresafer options.

Ambient Pressure Hydrogenation

Ambient pressure hydrogenations18,19

(Figures 3, 4a and 5) are frequentlyused in laboratories and generally saferto manipulate at smaller and largerscales in a properly functional chemi-cal fume hood using a suitable glass

Journal of Chemical Health & Safety, July/A

assembly (condenser, round bottomflask, cannula, septum and rubbertubing). An ambient pressure hydro-genation set-up is shown in Figures4a and 6.

Although hazards associated withthe catalyst, hydrogen and solvents stillpersist during ambient pressure hydro-genations, explosions associated withpressure are unlikely. In this method around bottom flask is equipped with acondenser and a bubbler (needle) forhydrogen supply; the same needle isused for nitrogen purging. Hydrogen isdirectly bubbled from a cylinder(equipped with low flow regulator)by placing a Tygon tube and a cannulainto the reaction mixture, comprising acatalyst and a substrate.

Loss of the solvent from the reactionis prevented using a cold-water con-denser (Figure 4a). This is critical for

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elevated temperature reactions. Sol-vent and catalyst loss should be moni-tored while purging the reactionmixture. Solvents such as methanoland ethanol will escape from the reac-tion mixture due to hydrogen purging.There is always a possibility of an ex-plosion from the catalyst that was con-verted into dry powder adsorbed withhydrogen. During transfer, a dry cata-lyst will disperse into air and aroundthe flask if nitrogen flow is not regulat-ed. Aqueous solvents (water and wa-ter: alcohol mixtures) are preferredover organic solvents for hydrogenbubbling due to their high boiling pointand low flammability.

A cold condenser is required toavoid a quick evaporation of the sol-vents from the reaction. A blanket ofinert gas can also be supplied, using afunnel, over the beaker containing thesolvent and catalyst being transferredto the reaction vessel (Figure 5).

Hazards

Ambient pressure hydrogenations arethe safest among all hydrogenations ifconducted using a proper SOP andreaction set-up inside a chemical fumehood. Hazards related to pressure aregenerally eliminated when hydrogengas is bubbled through a reaction mix-ture at ambient pressure. Also, ambientpressure hydrogenations are easy tomonitor using TLC, GC and HPLC,and reaction aliquots which are with-drawn easily without dis-assemblingthe reaction set-up. Although hazardsassociated with the catalyst and hy-drogen are still present, uncontrolledreactions are less likely. Analyzingplanned reactions to identifyhazards16 and determining appropri-ate controls are critical for all hydro-genation reactions in laboratory. The‘‘What if strategy’’20 (Table 1) devel-oped by the American ChemicalSociety’s Committee on ChemicalSafety’s can be employed to under-stand hazards associated with labora-tory hydrogenation at various steps.Table 1 highlights some of the safetyissues associated with ambient pres-sure hydrogenations; however variousfactors such as reaction scale, catalystnature, substrate and solvent shouldbe taken into consideration during ahazard assessment.

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[(Figure_4)TD$FIG]

Figure 4. Various laboratory hydrogenation techniques.

Balloon Method

Balloon hydrogenations are commonin the laboratory and are convenientfor small-scale hydrogenations.Balloons (Figure 6) used for hydroge-nations should be able to provide anoxygen-free atmosphere. Therefore,thick-wall, natural latex rubberballoons are appropriate for fillinghydrogen.

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Slight positive pressure is main-tained inside the balloon, which servesas a reservoir to accommodate pres-sure changes and to ensure net flow ofgas out of the vessel in the event of asmall leak in the system. During theprocess, the hydrogen balloon is at-tached to a Tygon tube to fit to athree-way adapter attached to a roundbottom flask (Figure 6). A three wayglass adapter attached to a Schlenk

Journal of Chem

line is used to supply the inert gas,vacuum21 and hydrogen to the flask.The following order is generally pre-ferred for the catalyst addition(Figure 7) to prevent flash fires arisingfrom the catalyst contact with solvent.

Hydrogen filling inside a balloonmust be conducted inside a chemicalfume hood. The balloon should not beover pressurized during hydrogenfilling. Degassing of a reaction mixture

ical Health & Safety, July/August 2016

[(Figure_6)TD$FIG]

Figure 6. Balloon method hydrogenation techniques (use of a three way adapter, balloon attachment and hydrogen addition toreaction mixture).

[(Figure_5)TD$FIG]

Figure 5. Ambient pressure hydrogenation.

is carried out using vacuum or purgingwith an inert gas (nitrogen or argon)before delivering hydrogen.

Shaker Hydrogenations

Parr reactors (shaker) are used forsmall scale hydrogenations in labo-ratory. A variety of shakers are avail-able (250–2,250 mL capacity, heating

Journal of Chemical Health & Safety, July/A

capacity up to 80 8C) from vendors.The instructional manual providedby the vendor must be followed forthe instrument and reaction bottleand/or vessel. A dedicated fume hoodor other suitable area with a properbarricade is recommended to protectresearchers from fire and run-awayreactions.

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High-Pressure HydrogenationsA high pressure reaction is generallydifficult to manage and also requireshands on experience with the reactorand detailed subject knowledge. Lim-ited alternatives22,23 are available forhigh pressure hydrogenations. Highpressure hydrogenations are generallycarried out using a suitable pressure

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[(Figure_7)TD$FIG]

Figure 7. Catalyst addition sequence during balloon hydrogenation.

Table1. AmbientPressureHydrogenationConducted at RefluxTemperature (Useof Flammable Solvent, Pyrophoric Catalyst andHydrogen Gas).

What if Answer Result Consequences Recommendations

Cold water supply tubingseparated fromcondenser duringreaction

Solvent used for rxn.Will easily escapefrom the condenser

Catalyst/rexn. mixturebecomes dry

Fire, explosions andflooding in the lab andloss of substrate

Make sure watertubing is attachedtightly, and waterpressure is controlledwell

Oxygen is not removedfrom rxn. mix. beforeintroducing hydrogen

Oxygen hydrogen mix.may form detonablemix.

Explosions and fire Assembly/productloss

Remove oxygencompletely from rxn.mix. beforeintroducing hydrogen

Catalyst dispersed insidethe fume hood duringtransfer

Enough catalyst is notavailable for the rxn.

Partial transformationof substrate

Fume hood fires,difficulty in productisolation

Proper method shouldbe used to transfercatalyst to the reactionvessel

Hydrogen flow is notcontrolled well

Catalyst will disperseon the wall of the flaskSolvent will easilyescape from reactionvessel

Enough catalyst is notavailable for rxn.Will reduce qty. ofsolvent from vessel

Difficulty to separatecatalyst from flask,incompletetransformation

Hydrogen flow mustbe controlled using adual stage regulator

vessel which is normally equipped withan agitator, heating system and a tem-perature controller. The responsibilityfor safe usage is that of the researchernot the vendor. A number of pressurevessels are available for high pressurehydrogenations from various vendors.High-pressure vessels are equippedwith a pressure release valve to allowthe safe venting of reaction contents in

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the event of pressure build-up; and toprevent runaway reactions.24

Hazards

Over pressurizing the pressure vesselscan cause fatal explosions and fire inthe laboratory. Numerous laboratoryfires and property damage have beenreported across the academic institu-tions associated to high pressure

Journal of Chem

hydrogenations. Therefore, a thoroughhazard assessment is very critical priorto conducting high pressure hydroge-nations (Table 2) along with hands-onexperience and subject knowledge.

Maintenance and service of the ves-sel must be completed according to thevendors guide. High pressure hydroge-nations should always be performedinside a chemical hood along with a

ical Health & Safety, July/August 2016

Table 2. High Pressure Hydrogenation Conducted at Higher Temperature.

What if Answer Result Consequences Recommendations

Vessel over-loaded withsolvent and reagent

Pressure will increaseinside the vessel

Discharge from vessel,uncontrolled rexn.

Fire andexplosions

Never fill reactors 2/3of their ability

Pure substrate is not usedfor hydrogenation

Hydrogenation willnot proceed smoothly

Runaway rexn.pressure rise

Difficulty inproductisolation

Use pure substrate forhydrogenations

Reaction temperatureis not controlled

High pressurebuild-up, substrateand productdecomposition

Runaway rexn. Fire andexplosion

Temperature of rexn.should be controlledprudently

Reaction mixture is notcooled before catalystseparation

Solvent will evaporatefast

Catalyst will get dryand possibility ofsolvent ignition

[29_TD$DIFF]Fire Reaction mix. shouldbe cooled beforecatalyst separation(filtration)

blast shield. Chemical fume hood sash-es should remain closed at all timesexcept during reaction set-up, additionof the chemical to the reaction vesselas necessary, and during work-up ofthe reaction mixture. When high pres-sure hydrogenations are conducted inthe laboratory, warning signs shouldbe posted on the chemical fume hoodto warn others in laboratory. Routinehigh pressure hydrogenations in a lab-oratory should be conducted in a des-ignated facility to contain explosionand fires. Leak detection and an emer-gency shutoff or excess flow controldevices are useful for controlling theleak and preventing pressure build-up.

Continuous-Flow Hydrogenations

Continuous-flow hydrogenations (Fig-ure 8)22,23 are safer options for small as

[(Figure_8)TD$FIG]

Figure 8. Continuous-flow

Journal of Chemical Health & Safety, July/A

well as large scale laboratory hydroge-nations. Continuous-flow hydrogena-tion systems are superior as comparedto batch hydrogenations in terms ofhydrogen handling, catalyst manipula-tion and pressure. During continuous-flow hydrogenations, the catalyst isrestricted in a closed cartridge andnever comes in contact with air whichreduces flash fire and other solvent/catalyst hazards in a laboratory set-up.

SAFETY

Hydrogen Manipulations

There are many regulations and stan-dards which apply to hydrogen.25–27

Hydrogen gas should be stored inwell-ventilated areas and away fromoxidizers, open flames, sparks and

hydrogenation set-up.

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other sources of heat and ignition.28

Manipulations involving hydrogen aresafely conducted when proper guide-lines and techniques are applied dur-ing hydrogenations. Hydrogen leaksthrough lines are difficult to detectby humans. Hydrogen is a nontoxicgas classified as a simple asphyxiant.Regulators, joints, flanges, diaphragms,gaskets, and various seals and fittingsused for hydrogen manipulations canbecome a source of leaks due to incor-rect alignment and improper mainte-nance. Any hydrogen delivery systemin combination with a reaction set-upshould be checked for any leak beforepressurizing the line and equipment.Inert gases should be used to checkfor leaks in the lines as well as pres-sure vessels. Hydrogen has no thresh-old limit value (TLV). The primaryhazard associated with any form ofhydrogen is inadvertently producing aflammable mixture, leading to a fireand detonation. An explosion cannotoccur without an oxidizer inside avessel or cylinder when hydrogen iscontained.

Oxygen should be replaced withnitrogen from the mixture of catalyst,solvent and substrate (Figure 9) beforeintroducing hydrogen to the reactionmixture. The hydrogen pressure of thevessel shouldbemonitoredprudently toavoid any runaway29 reaction. Thereshould be no ignition sources close toa hydrogenation reaction such as openflames, electrical equipment, or heatingequipment (Figure 10). Static electricitycan also generate sparks that will ignitehydrogen-air or hydrogen-oxygen

21

[(Figure_11)TD$FIG]

Figure 11. Catalyst fire inside trashreceptacle.

[(Figure_9)TD$FIG]

Figure 9. Hydrogen removal from reaction mixture using (a) nitrogen and (b)vacuum.

[(Figure_10)TD$FIG]

Figure 10. Best practices for catalyst, hydrogen and solvent handling.

mixtures. Many common articles, suchas hair or fur when combed or a leatherbelt operating on a machine can gener-ate a static electricity.

Incident 1

A small fire was started while a re-searcher was working on a hydrogena-tion catalyzed by palladium-on-carbon. Upon completion of the hy-drogenation, the researcher performedthree vacuum/purge cycles with drynitrogen gas in order to eliminateany remaining hydrogen gas in orderto reduce the risk of ignition duringfiltration. The palladium-on-carbonwas filtered through a sintered glassfunnel covered with Celite 545. Thefilter cake was subsequently washedwith wet methanol and covered withsand. The contents of the funnel weredumped into a waste container andcovered with additional sand. A fire

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was ignited when the researcherattempted to transfer a minute amountof residual palladium-on-carbon fromthe funnel to a designated waste con-tainer.

The fire was quickly extinguishedwith a dry chemical fire extinguisher.No one was injured during the incidentand there was no damage to the facili-ty. The researcher performing the re-action was well aware of theprecautions required to safely handlepalladium-on-carbon.

The safety office recommendedmaking a wet slurry, by adding waterto the palladium-on-carbon Celite 545mixture, prior to transferring the spentpalladium-on-carbon to a designatedwaste container. It must be kept awayfrom any combustible materials.

In another palladium-on-carbonfire, a researcher was performinga hydrogenation reaction using palla-

Journal of Chem

dium on carbon as a catalyst to reducethe nitro group using standard proto-col. Upon completion of filtration, thecatalyst was separated from diatoma-ceous earth pad and mistakenly tossedinto a normal trash receptacle. Thatevening the material was placed inthe garbage, including the residual cat-alyst which was contaminated withdiatomaceous earth. It ignited thecombustible materials in the trash re-ceptacle (Figure 11).

This trash receptacle fire could havebeen avoided using an appropriate dis-posal container for the spent catalyst inthe lab.

All sources of ignition should be iso-lated from hydrogen cylinders, reactionset-up. Hydrogen cylinders must bekept away from oxygen, chlorine andother incompatible materials. Never ex-change regulators, hoses and otherappliances used for hydrogen gas. Aregulator or step-down pressure valveshould be used to pressurize low-pres-sure equipment from a high-pressuresource. After pressurizing equipmentfrom a high-pressure source, the equip-ment should either be disconnected orthe connecting piping/tubing should bevented to atmospheric pressure. Thiswill prevent the accidental buildup ofexcessive pressure inside the low-pres-sure equipment due to leakage from thehigh-pressure source.

Catalyst Manipulation

Proper selection of a suitable catalystand solvent and determining their ratiois critical for a catalytic hydrogenation.All catalysts should be considered po-tentially pyrophoric and must behandled prudently. However, a drycatalyst often requires special attention

ical Health & Safety, July/August 2016

[(Figure_12)TD$FIG]

Figure 12. Proper storage of spent catalyst.

Figure 13. Pd/C catalyst filtration system.

because the potential of igniting flam-mable materials is greater than with awet catalyst. The risk of spontaneousignition should be reduced by coolingboth the catalyst and the organic mate-rials before performing the mixing pro-cess under inert gas atmosphere, suchas nitrogen.

Spent catalysts with absorbed hy-drogen may ignite if dried in the air,especially in the presence of organicmaterials. Therefore, used and filteredcatalysts should be kept water-wet(Figure 12) and out of contact withcombustible solvents and vapors.

Even fresh Pd/C catalyst can catchfire from a small static charge devel-oped from scratching the catalyst bag.Therefore, transfer of the catalystshould be avoided directly from baginto reaction vessel.

Incident 2

A researcher was cleaning out a smallgas chromatography vial inside achemical fume hood using ethyl ace-tate, when the researcher spilled a fewdrops of ethyl acetate onto a smallcloth pad he had in his hood. Smallsparks appeared on the mat whichthen caught on fire as the ethyl acetateburned. The researcher then noticedthat the test tube rack with ethyl ace-tate-hexanes solvent mixtures hadcaught on fire. The fire was mostlycontained in the back far right cornerof the hood and minimal cosmeticdamage to the hood occurred. Theinitial spark likely began from a smallamount of activated palladium carbon(Pd/C) on the pad mentioned. Theresearcher had used Pd/C catalystto set up a hydrogenation the nightbefore. The drops of solvent must have

Journal of Chemical Health & Safety, July/A

disturbed the reagent in the mat, whichcaused the spark and subsequent fire.

To avoid similar incidents after hydro-genations, prompt cleanup of spent cat-alyst, solvent and chemical fume hoodsurfaces should be conducted.

Catalyst Filtration/Isolation

Most catalyst associated fires insidelaboratories occur during catalyst sep-aration (filtration), therefore applyingprudent steps are critical to avoid fire.Residual hydrogen should be removedcompletely from the reaction mixturebefore catalyst filtration separation (fil-tration) using inert gas (N2 bubbling;Figure 9a) or by applying a low vacuum(Figure 9b) to the reaction vessel. Dur-ing catalyst filtration, inert atmospherecan be generated using a plastic funnel[(Figure_13)TD$FIG]

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as shown in Figure 13. Catalyst filtra-tion in the laboratory is generally car-ried out using a bed of Celite (or similarfilter aid).

Hydrogenations conducted at an el-evated temperature regularly requirecooling before work-up to avoid thecatalyst drying. Use of high vacuumpump for catalyst filtration will drythe catalyst residue and filtrationbed. The residual catalyst that sticksto the flask surface and joints of thevessel should be removed using addi-tional solvent (water or polar solventspreferred) with proper safeguards.When the residual catalyst is difficultto remove from the surface of the re-action vessel, it should be covered withwater to keep the catalyst wet.

The vacuum tube from the filtrationflask should be detached before dryingthe catalyst bed. Several mL of watershould be added to the cake to keep thecatalyst wet. Never leave the catalystfiltration unattended. Applying lowvacuum to a reaction vessel will pre-vent bumping the reaction mixture in-to vacuum system. The vacuum systemcontaminated with the catalystrequires proper cleaning and may re-quire an oil change for the pump.

Incident 3

A researcher was performing a Raneynickel catalyst filtration from a reaction

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SUMMARY

[(Figure_14)TD$FIG]

Figure 14. Catalyst fire during filtration.

mixture using a Celite pad. A wateraspirator was used for filtration(Figure 14). The researcher left thescene after transferring all reaction mix-ture to the funnel. After five minutes thecatalyst ignited causing a small fire in-side the filtration funnel.

This incident could have beenavoided if the catalyst was kept wetusing water during filtration, and thecatalyst filtration was not unattended.

A dedicated waste jar containingwater is preferred to collect the spentcatalyst recovered from hydrogena-tions. Removal of the residual catalystfrom filter paper and Celite pad is gen-erally difficult due to nature of thecatalyst. Therefore, those items shouldbe submerged into water until disposedof safely from the lab. Laboratory scalehydrogenations typically consume alow quantity of the desired catalystfor hydrogenations; therefore the cat-alyst is not recycled through vendors.When hydrogenation catalysts areused often for the synthesis purpose,two separate small glass containersshould be used for storage purposeand one for storing unwanted catalystand one for paper and Celite. The fun-nel contaminated with a residual cata-lyst should be submerged into a waterbath before the catalyst becomes dry.Recovery and reuse of the catalyst isrecommended when a large quantity ofspent catalyst is generated in labs.

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Some catalysts are then sold for a highprice. Similarly, if there is any catalystcontamination in the Celite pad, theupper layer of the pad should be re-moved for disposal or storage purpose.

Catalyst should remain wet duringentire hydrogenation manipulation.Palladium on carbon recovered fromcatalytic hydrogenation reactions byfiltration requires careful han-dling,17,24 because it is usually saturat-ed with hydrogen and will ignitespontaneously on exposure to air.The filter cake should never be allowedto dry, and the moist material shouldbe added to a large quantity of waterand disposed of properly.

BEST PRACTICES FOR LABORATORYHYDROGENATIONS

� S

elect a vessel/set-up such as areaction flask, pressure vessel andshakers appropriate for the experi-ment.

� R

eview the operating procedures forthe apparatus and inspect the vesselbefore each experiment. Glass ves-sels with a crack are at risk to breakunder pressure.

� R

emove all oxygen from the vessel/solutions either using nitrogen orvacuum using a Schlenk line.

� S

tay well below the rated safe-pressure limit of the vessel due to

Journal of Chemica

exothermic nature of reactions orintermediate unpredictability.

� M onitor the reaction prudently and

do not leave hydrogenation reac-tions unattended.

� A ll catalysts must be handled pru-

dently because of their high reactivi-ty before and after use.

� K eep a bucket of sand nearby

manipulations to quickly smother asmaller fire.

� U se of gas burners, open flames and

oxidizers should be avoided near thehydrogenation set-up.

Laboratory hydrogenations are usefulfor chemical transformations at gramas well as multi-gram scales. Severalhigh risk operations such as catalysttransfer, use of high pressure hydrogencylinders, hydrogen purging, vesselpressurization and catalyst manipula-tions are involved throughout the hy-drogenation. Hydrogenations that areconducted at ambient pressure aregenerally safer compared to high pres-sure. Hazard identifications and theirmitigations are critical for small as wellas large scale hydrogenations. Addi-tional care should be taken wheneversubstrates or intermediates containingnitro groups are reduced using catalyt-ic hydrogenations. Inexperiencedresearchers should use the lowest scalereduction (hydrogenation) for highhazardous or high pressure reductionand should seek advice from an expe-rienced researcher. First time users ofhigh pressure vessels should practicethe manipulations including vessel op-eration without using catalyst andflammable solvents. The spent catalystmust be kept wet at all times. Drycatalysts are prone to fire. Special pre-cautions should be taken while work-ing with high pressure vessels. Safepressure limits provided by a vendorshould be followed for any high pres-sure vessel in order to avoid the run-away reactions29 caused by reactionexothermicity or intermediate unpre-dictability. The proper choice of per-sonal protective equipment (PPE) isimperative. A proper risk assessmentshould be performed prior to begin-ning any hydrogenations to identify

l Health & Safety, July/August 2016

the proper PPE for the specific opera-tions.

ACKNOWLEDGEMENTSI sincerely thank the UW-Chemistryfaculty/staff, for providing useful infor-mation about hydrogenations to devel-op this document. I also thank Dr. PaulUmbeck, Dr. Rob McClain and Dr.Neal Langerman for helpful discussion.

Note: The information provided inthis manuscript is the author’s opinionand does not represent the opinion oforganizations where I worked or amworking with. ‘‘I elucidated my argu-ments from experience’’. This manu-script serves only as a guideline and isno way intended to serve as the soletraining source for a procedure, meth-od or task. All references or mention ofcommercial products, trade names,trademarks, manufacture, distributoror otherwise, are meant to be examplesand do not represent endorsement of aproduct or service.

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