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Student Manual OACP I (2018) ETH Zürich · OACP I 1 Laboratory Course OACP I (2018) (Praktikum Organische & Anorganische Chemie I) Protocols Student Manual

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Student Manual OACP I (2018)

ETHZürich·OACPI 1

Laboratory Course OACP I (2018)

(Praktikum Organische & Anorganische Chemie I)

Protocols

Student Manual

Student Manual OACP I (2018)

ETHZürich·OACPI 2

TableofContentsWeek1:Esterification/Distillation...................................................................................3

1a)Isobutylacetate(cherry,raspberry,strawberryflavor).......................................................31b)Isobutylformate(raspberryflavor)......................................................................................41c)Propylacetate(pearflavor)..................................................................................................51d)Pentylformate(bananaflavor)............................................................................................6

Week2:AldolCondensation/Recrystallization...............................................................72a)(E,E)-Dibenzylideneacetone.................................................................................................72b)(E)-Chalcone.........................................................................................................................82c)(E)-(2-Nitrovinyl)benzene.....................................................................................................9

Week3:GrignardReaction/ColumnChromatography..............................................103a)Diphenylmethanol..............................................................................................................103b)Triphenylmethanol.............................................................................................................113c)Cyclohexanecarboxylicacid................................................................................................12

Week4:TheWittig(&HWE)Reaction............................................................................134a)Ethyl2-cyclohexylideneacetate.........................................................................................134b)(Cyclohexylidenemethyl)benzene.....................................................................................144c)1-Methylene-1,2,3,4-tetrahydronaphthalene....................................................................15

Week5:ElectrophilicAromaticSubstitution..................................................................165a)Methylm-nitrobenzoate....................................................................................................165b)(E)-1-(phenyldiazenyl)naphthalen-2-ol..............................................................................175c)(4-Nitrophenyl)acetonitrile................................................................................................18

Week6:Aromatic&HeteroaromaticChemistry............................................................196a)2-Phenylindolizine.............................................................................................................196b)3,5-Diphenylisoxazole........................................................................................................206c)O-benzylhydroxylamine.....................................................................................................20

Week7:NucleophilicAromaticSubstitution..................................................................227a)1-Nitro-4-phenoxybenzene................................................................................................227b)1-Nitro-4-(3-phenylpropoxy)benzene................................................................................237c)4-Nitro-1-(1-methylethoxy)benzene..................................................................................24

Week8:ElectrophilicAdditionstoAlkenes....................................................................258a)2-p-Tolyloxirane.................................................................................................................258b)2-(4-tert-Butylphenyl)ethanol...........................................................................................268c)2-Bromo-1-p-tolylethanol..................................................................................................27

Weeks9-11:Multi-StepSynthesisofLigands.................................................................289a)(R)-1,1'-Binaphthyl-2,2'-diol(BINOL).................................................................................289b)Diphenylbutadien..............................................................................................................319c)4-Ethylbenzoicacid............................................................................................................34

Student Manual OACP I (2018)

ETHZürich·OACPI 3

Week1:Esterification/Distillation

1a)Isobutylacetate(cherry,raspberry,strawberryflavor)

Preparation:2-Methylpropan-1-ol(250mmol)andaceticacid(2.4equiv)arecombinedina250mlflaskequippedwitha stirringbar.Sulfuricacid (5ml) is carefullyaddeddropwisewhile stirring iscontinued.Arefluxcondenserisplacedontheflask,thecoolingwateristurnedon,andthereactionmixtureisheatedtoreflux(temperature?).After2-3hoursthereactioniscompleteandthemixtureiscooledtoRT.Themixtureispouredinaseparatorfunnelandtheflaskisrinsedwithabitofwater.Then,addasmuchwateruntilthewaterphasehastwicethevolumeoftheorganicphase.Thetwophasesareseparated,theorganicphaseis kept in an Erlenmeyer flask, and the water phase is extracted with dichloromethane of equalvolume. The combined organic layers are washed with saturated sodium hydrogen carbonate(careful:CO2evolution)anddriedovermagnesiumsulfate,followedbyfiltrationandconcentrationontherotaryevaporator.Purification:Theresidueisdistilledatatmosphericpressure.Analysis:Odor,IR.Fillinthistablebeforeyoubegin:

Reactant MW Equiv Moles Mass Volume Purity2-Methylpropan-1-ol 1.00 250mmol Aceticacid 2.40 Sulfuricacid 5.0ml Product MW Yield Moles Mass BP 115-117°C

Student Manual OACP I (2018)

ETHZürich·OACPI 4

1b)Isobutylformate(raspberryflavor)

Preparation:2-Methylpropan-1-ol(300mmol)andformicacid(2.00equiv)arecombinedina250mlflaskequippedwitha stirringbar.Sulfuricacid (5ml) is carefullyaddeddropwisewhile stirring iscontinued.Arefluxcondenserisplacedontheflask,thecoolingwateristurnedon,andthereactionmixtureisheatedtoreflux(temperature?).After2-3hoursthereactioniscompleteandthemixtureiscooledtoRT.Themixtureispouredinaseparatoryfunnelandtheflaskisrinsedwithabitofwater.Then,addasmuchwateruntilthewaterphasehastwicethevolumeoftheorganicphase.Thetwophasesareseparated,theorganicphaseis kept in an Erlenmeyer flask, and the water phase is extracted with dichloromethane of equalvolume. The combined organic layers are washed with saturated sodium hydrogen carbonate(careful:CO2evolution)anddriedovermagnesiumsulfate,followedbyfiltrationandconcentrationontherotaryevaporator.Purification:Theresidueisdistilledatatmosphericpressure.Analysis:Odor,IR.Fillinthistablebeforeyoubegin:

Reactant MW Equiv Moles Mass Volume Purity2-Methylpropan-1-ol 1.00 300mmol Formicacid 2.00 Sulfuricacid 5.0ml Product MW Yield Moles Mass BP 98°C

Student Manual OACP I (2018)

ETHZürich·OACPI 5

1c)Propylacetate(pearflavor)

Preparation: Propanol (200mmol) and acetic acid (2.50 equiv) are combined in a 250 ml flaskequipped with a stirring bar. Sulfuric acid (5 ml) is carefully added drop wise while stirring iscontinued.Arefluxcondenserisplacedontheflask,thecoolingwateristurnedon,andthereactionmixtureisheatedtoreflux(temperature?).After2-3hoursthereactioniscompleteandthemixtureiscooledtoRT.Themixtureispouredinaseparatoryfunnelandtheflaskisrinsedwithabitofwater.Then,addasmuchwateruntilthewaterphasehastwicethevolumeoftheorganicphase.Thetwophasesareseparated,theorganicphaseis kept in an Erlenmeyer flask, and the water phase is extracted with dichloromethane of equalvolume. The combined organic layers are washed with saturated sodium hydrogen carbonate(careful:CO2evolution)anddriedovermagnesiumsulfate,followedbyfiltrationandconcentrationontherotaryevaporator.Purification:Theresidueisdistilledatatmosphericpressure.Analysis:Odor,IR.Fillinthistablebeforeyoubegin:

Reactant MW Equiv Moles Mass Volume PurityPropanol 1.00 200mmol Aceticacid 2.50 Sulfuricacid 5.0ml Product MW Yield Moles Mass BP 102°C

Student Manual OACP I (2018)

ETHZürich·OACPI 6

1d)Pentylformate(bananaflavor)

Preparation: Pentanol (200mmol) and formic acid (2.50 equiv) are combined in a 250 ml flaskequipped with a stirring bar. Sulfuric acid (5 ml) is carefully added drop wise while stirring iscontinued.Arefluxcondenserisplacedontheflask,thecoolingwateristurnedon,andthereactionmixtureisheatedtoreflux(temperature?).After2-3hoursthereactioniscompleteandthemixtureiscooledtoRT.Themixtureispouredinaseparatoryfunnelandtheflaskisrinsedwithabitofwater.Then,addasmuchwateruntilthewaterphasehastwicethevolumeoftheorganicphase.Thetwophasesareseparated,theorganicphaseis kept in an Erlenmeyer flask, and the water phase is extracted with dichloromethane of equalvolume. The combined organic layers are washed with saturated sodium hydrogen carbonate(careful:CO2evolution)anddriedovermagnesiumsulfate,followedbyfiltrationandconcentrationontherotaryevaporator.Purification:Theresidueisdistilledatatmosphericpressure.Analysis:Odor,IR.Fillinthistablebeforeyoubegin:

Reactant MW Equiv Moles Mass Volume PurityPentanol 1.00 200mmol Formicacid 2.50 Sulfuricacid 5.0ml Product MW Yield Moles Mass BP 132°C

Student Manual OACP I (2018)

ETHZürich·OACPI 7

Week2:AldolCondensation/Recrystallization

2a)(E,E)-Dibenzylideneacetone

Preparation:Toa500mlone-neckedflaskequippedwithastirringbarisaddedaNaOHsolution(5equiv)in50mlH2O.Then,ethanol(33ml)isaddedwithstirring,andthemixtureiscooledto0°C.Benzaldehyde(47mmol,2.05equiv)andacetone(1equiv)areaddedtothereactionmixtureslowlyduring15min.Aftertheadditionthereactionmixtureisstirredfor1hatRT.Themixtureisfiltered,andthesolidiswashedwithwater(3×50ml).Purification:Thesolidisrecrystallized.Findthepropersolventorsolventmixture!Analysis:TLC,meltingpoint,IR.Fillinthistablebeforeyoubegin:

Reactant MW Equiv Moles Mass Volume PurityAcetone 1.00 Benzaldehyde 2.05 47mmol Sodiumhydroxide 5.00 Product MW Yield Moles Mass MP

Student Manual OACP I (2018)

ETHZürich·OACPI 8

2b)(E)-Chalcone

Preparation: A solution of acetophenone (50mmol), benzaldehyde (50mmol) and NaOH(1.00equiv)in50mlanhydrousmethanolisstirredatRTfor24h.Thereactionmixtureturnsyellow.After cooling to 0°C using an ice bath, the product crystallizes (if necessary seed to initiatecrystallization).Filterthesolidandwashcarefullywithice-coldethanol.Concentrationofthefiltratewillprovideasecondportionofproduct.Purification:Thesolidisrecrystallized.Findthepropersolventorsolventmixture!Analysis:TLC,meltingpoint,IR.Fillinthistablebeforeyoubegin:

Reactant MW Equiv Moles Mass Volume PurityAcetophenone 1.00 50mmol Benzaldehyde 1.00 50mmol Sodiumhydroxide 1.00 Product MW Yield Moles Mass MP

Student Manual OACP I (2018)

ETHZürich·OACPI 9

2c)(E)-(2-Nitrovinyl)benzene

Preparation: To a solution of nitromethane (55mmol) in MeOH (10ml) is added benzaldehyde(50mmol).Themixtureiscooledto0°C,andanaqueoussolutionofNaOH(2M;1.10equiv)isaddedoveraperiodof30min.Stirringiscontinuedforanother30minat0-5°C.ThemixtureisdilutedwithH2O (25ml)andpouredontocrushed icecontaining8mlofconcentratedHCl.The formedyellowprecipitateisfilteredandbrieflydriedinvacuo.Purification:Thesolidisrecrystallized.Findthepropersolventorsolventmixture!Analysis:TLC,meltingpoint,IR.Fillinthistablebeforeyoubegin:

Reactant MW Equiv Moles Mass Volume PurityNitromethane 1.10 55mmol Benzaldehyde 1.00 50mmol Sodiumhydroxide 1.10 Product MW Yield Moles Mass MP

Student Manual OACP I (2018)

ETHZürich·OACPI 10

Week3:GrignardReaction/ColumnChromatography

3a)Diphenylmethanol

Preparation: Magnesium turnings (2.0g) are suspended in Et2O (15ml) in a three-necked flaskequipped with a stir bar, dropping funnel, and reflux condenser. About 1/20 of bromobenzene(50mmol) is added. To ensure formation of the Grignard reagent (turbidity), themixture can beheatedgentlywithawarmwaterbathand/orafewcrystalsofI2canbeadded.Oncetheformationofthereagenthasstarted,therestofthebromobenzeneisdissolvedinEt2O(20ml)andthenslowlyadded to the reactionmixture (ether should be boiling gently; takes ca. 30min). Themixture isheatedto reflux for30min.Then it iscooledto0°C,andasolutionofbenzaldehyde (37mmol) inEt2O(5ml)isadded.StirringiscontinuedatRTfor1h.Then the mixture is poured into ice-cold saturated aqueous NH4Cl (20ml). The phases areseparated,andtheaqueousphaseextractedwithEt2O(2x10ml).ThecombinedorganicphasesarewashedwithsaturatedaqueousNaHCO3andsaturatedaqueousNaCl,thendried(Na2SO4),filtered,andconcentratedinvacuo.Purification: The residue is purified by flash column chromatography. Find the proper solvent orsolventmixture!Analysis:TLC,meltingpoint,IR.Fillinthistablebeforeyoubegin:

Reactant MW Equiv Moles Mass Volume PurityBenzaldehyde 1.00 37mmol Bromobenzene 50mmol Magnesium 2.00g Product MW Yield Moles Mass MP

Student Manual OACP I (2018)

ETHZürich·OACPI 11

3b)Triphenylmethanol

Preparation: Magnesium turnings (1.0g) are suspended in Et2O (15ml) in a three-necked flaskequippedwith a stir bar, dropping funnel, and reflux condenser. About 1/20 of bromobenzene (41mmol)isadded.ToensureformationoftheGrignardreagent(turbidity),themixturecanbeheatedgentlywithawarmwaterbathand/orafewcrystalsofI2canbeadded.Oncetheformationofthereagent has started, the rest of the bromobenzene is dissolved in Et2O (20ml) and then slowlyadded to the reactionmixture (ether should be boiling gently; takes ca. 30min). Themixture isheatedtorefluxfor30min.Thenit iscooledto0°C,andasolutionofbenzophenone(32mmol)inEt2O(30ml)isadded.Afteradditionthesolutionisheatedtorefluxfor20minutes.AftercoolingtoRT,add10gofcrushedicefollowedby10mLhalf-concentratedHCl.ThemixtureisstirreduntilthephasesseparateandisthenextractedwithEt2O(2x30ml).Thecombinedorganicphases arewashedwith saturatedaqueousNaHCO3andwater, thendried (Na2SO4), filtered, andconcentratedinvacuo.Purification:Theresidueispurifiedbyflashcolumnchromatography.Incaseofahighyieldnotallcrudeproductneedstobepurified.Findthepropersolventorsolventmixture!Analysis:TLC,IR.Fillinthistablebeforeyoubegin:

Reactant MW Equiv Moles Mass Volume PurityBenzophenone 1.00 32mmol Bromobenzene 41mmol Magnesium 1.00g Product MW Yield Moles Mass

Br Mg MgBr

O

OH

Student Manual OACP I (2018)

ETHZürich·OACPI 12

3c)Cyclohexanecarboxylicacid

Preparation: Magnesium turnings (2.0g) are suspended in Et2O (15 ml) in a three-necked flaskequippedwith a stir bar, dropping funnel, and reflux condenser. About 1/20 of bromocyclohexane(50mmol) is added. To ensure formation of the Grignard reagent (turbidity), themixture can beheatedgentlywithawarmwaterbathand/orafewcrystalsofI2canbeadded.Oncetheformationofthereagenthasstarted,therestofthebromocyclohexaneisdissolvedinEt2O(30mL)andthenslowlyaddedtothereactionmixture(ethershouldbeboilinggently).Aftertheadditioniscompletethemixtureisheatedtorefluxfor15min.Thenitiscooledtoroomtemperatureanddilutedwith50mLofdryEt2O.Wrapapproximately500mmolofdryiceinaclothandcrushitwithahammer,beingcarefultokeepthe ice inside the towel tominimizemoisture. The crushed dry ice should be put into a 500mLbeakerandtheGrignardsolutionimmediatelycarefullypouredoverit.Allowthereactiontostanduntil the carbon dioxide has completely evaporated and add 2 M HCl (35 mL). The phases areseparated,andtheaqueousphaseextractedwithEt2O(2x20ml).Thecombinedorganicphasesaredried(Na2SO4),filtered,andconcentratedinvacuo.Purification: The residue is purified by flash column chromatography. Find the proper solvent orsolventmixture!StainTLCwithKMnO4staininordertoseetheproduct.Analysis:TLC,IR.Fillinthistablebeforeyoubegin:

Reactant MW Equiv Moles Mass Volume PurityBromocyclohexane 1.00 50mmol CarbonDioxide Magnesium 2.00g Product MW Yield Moles Mass MP

Br Mg MgBr CO2O

OH

Student Manual OACP I (2018)

ETHZürich·OACPI 13

Week4:TheWittig(&HWE)Reaction

4a)Ethyl2-cyclohexylideneacetate

Preparation: NaH (60% in oil; 480mg, 12mmol) under nitrogen atmosphere is suspended in dryTHF(8ml),andthemixtureiscooledto0°C.Triethylphosphonoacetate(3.0ml,15mmol)isaddeddropwise, and themixture is stirred for 30min at RT. Then it is cooled to 0°C and a solution ofcyclohexanone (1.0g, 10mmol) inTHF (2ml) is addeddropwise.The resulting reactionmixture isstirredatRTfor20h.Then,saturatedaqueousNH4Clsolutionisadded,andthemixtureisextractedwithEt2O(2x20ml).Thecombinedorganic layersarewashedwithbrine,dried(MgSO4),filtered,andconcentratedinvacuo.Purification:Theresidueispurifiedbyflashcolumnchromatography.Analysis:TLC,IR.Fillinthistablebeforeyoubegin:

Reactant MW Equiv Moles Mass Volume PurityCyclohexanone 1.00 10mmol 1.00g Triethylphosphonoacetate 15mmol 2.98ml Sodiumhydride 12mmol 0.48g - 60%Product MW Yield Moles Mass

Student Manual OACP I (2018)

ETHZürich·OACPI 14

4b)(Cyclohexylidenemethyl)benzene

Preparation: Benzyltriphenylphosphonium chloride (15 mmol) is added to a round bottom flaskunder nitrogen atmosphere and suspended in dry THF (19mL). At room temperature add a 12%solutionoftBuOK(15mmol) inTHFdropwise.Themixturewillturnbrightredandisstirredfor30minutes. Cyclohexanone (10 mmol) in THF (3 mL) is added dropwise and the mixture is stirredovernight.Thereactionisquenchedwith1MHClandmostTHFremovedinvacuo.TotheresidueisaddedwaterandextractedwithMTBE(2x30mL).Thecombinedorganiclayersaredried(Na2SO4),filtered,andconcentratedinvacuo.Purification:TheresidueispurifiedbyflashcolumnchromatographyAnalysis:TLC,IR.Fillinthistablebeforeyoubegin:

Reactant MW Equiv Moles Mass Volume PurityCyclohexanone 1.00 10mmol Benzyltriphenylphosphoniumchloride

15mmol

12%tBuOKinTHF 15mmol 14.0mL 12%Product MW Yield Moles Mass

P+Cl-

tBuOK

THFP

O

Student Manual OACP I (2018)

ETHZürich·OACPI 15

4c)1-Methylene-1,2,3,4-tetrahydronaphthalene

Preparation: Methyltriphenylphosphonium bromide (15mmol) is added to a round bottom flaskunder nitrogen atmosphere and suspended in dry THF (19mL). At room temperature add a 12%solution of tBuOK (15mmol) in THF dropwise. Themixture will turn yellow and is stirred for 30minutes.a-tetralone(10mmol)inTHF(3mL)isaddeddropwiseandthemixtureisstirredovernight.The reaction isquenchedwith1MHClandmostTHFremoved invacuo.To the residueaddwaterandextractwithMTBE (2x 30mL). The combinedorganic layers aredried (Na2SO4), filtered, andconcentratedinvacuo.Purification:TheresidueispurifiedbyflashcolumnchromatographyAnalysis:TLC,IR.Fillinthistablebeforeyoubegin:

Reactant MW Equiv Moles Mass Volume Purityα-Tetralone 1.00 10mmol Methyltriphenylphosphoniumbromide

15mmol

12%tBuOKinTHF 15mmol 14mL 12%Product MW Yield Moles Mass MP

P+ CH3Br-

tBuOK

THFP CH2

O

Student Manual OACP I (2018)

ETHZürich·OACPI 16

Week5:ElectrophilicAromaticSubstitution

5a)Methylm-nitrobenzoate

Preparation:Intoaround-bottomedflaskfittedwithastirbarareplacedconcentratedsulfuricacid(20ml)cooledto0°Candmethylbenzoate(75mmol).Themixture iscooledto0-10°Candthen,whilestirring, there isaddedgradually,bymeansofadropping funnel,amixtureofconcentratednitric acid (1.30 equiv) and concentrated sulfuric acid (1.56 equiv). During the addition of thenitrating acid,which requires about onehour, the temperature of the reactionmixture should bekeptwithintherange5-15°C.Afterthenitricacidhasbeenadded,stirringiscontinuedfor15min;themixtureisthenpoureduponcrushedice(ca.60g).Thecrudemethylm-nitrobenzoateseparatesasasolidandisfilteredoffbymeans of suction andwashedwithwater. The product is placed in a flask and stirred in ice-coldmethanol (10ml) in order to remove a small amount ofo-nitrobenzoic ester and other impuritiesthat are present. The cooled mixture is then filtered by means of suction, washed with anotherportionofcoldmethylalcohol(5ml),andthesoliddried.Purification:Thesolidisrecrystallized.Findthepropersolventorsolventmixture!Analysis:TLC,meltingpoint,IR.Fillinthistablebeforeyoubegintheexperiment:

Reactant MW Equiv Moles Mass Volume PurityMethylbenzoate 1.00 75mmol Nitricacid 1.30 70%Sulfuricacid 1.56 Product MW Yield Moles Mass MP

Student Manual OACP I (2018)

ETHZürich·OACPI 17

5b)(E)-1-(phenyldiazenyl)naphthalen-2-ol

Preparation:Toa100mLErlenmeyerflaskequippedwithathermometerandamagneticstirbar,add13gice,5mLwaterand2.5mLconc.HCl.Tothisanilinehydrochloride(11mmol)isaddedandthencooledto0°C.AsolutionofNaNO2(11mmol)inwater(3mL)isaddeddropwise,whilestirringvigorously.Important:Thetemperatureshouldnotexceed5°C.Chargeaseparate250mLErlenmeyerflaskwith2-Napthol(10mmol)in40mLof1MNaOHWhile stirringandcooling, add thepreviouslyprepareddiazoniumsalt solutionportionwise.Aftertheadditionstirthereactionfor5minutesandisolatetheorangeproductbysuctionfiltration.Purification:Thesolidisrecrystallized.Findthepropersolventorsolventmixture!Analysis:TLC,meltingpoint,IR.Fillinthistablebeforeyoubegintheexperiment:

Reactant MW Equiv Moles Mass Volume PurityAnilineHydrochloride 1.10 11mmol SodiumNitrite 1.10 11mmol 2-Napthol 1.00 10mmol Product MW Yield Moles Mass MP

NH3+ Cl– NaNO2 N2+ Cl–OH

OHN N

Student Manual OACP I (2018)

ETHZürich·OACPI 18

5c)(4-Nitrophenyl)acetonitrile

Preparation:Amixtureofconcentratedsulfuricacid(14ml)andconcentratednitricacid(14ml) iscooledto10°C.Withinonehourbenzylcyanide(43mmol)isaddeddropwiseinsuchawaythattheinternaltemperaturedoesnotexceed20°C.Aftertheaddition iscompletedthemixture isstirredfor1hatRT.Thenthemixtureispouredontocrushedice(60g),filtered,anddriedinvacuo.Purification:Thesolidisrecrystallized.Findthepropersolventorsolventmixture!Analysis:TLC,meltingpoint,IR.Fillinthistablebeforeyoubegintheexperiment:

Reactant MW Equiv Moles Mass Volume PurityBenzylcyanide 1.00 43mmol Nitricacid 13.8ml 70%Sulfuricacid 13.8ml Product MW Yield Moles Mass MP Note:Benzylcyanide=Phenylacetonitrile

Student Manual OACP I (2018)

ETHZürich·OACPI 19

Week6:Aromatic&HeteroaromaticChemistry

6a)2-Phenylindolizine

Preparation:a) Pyridinium salt: To a boiling solution of 2-methylpyridine (3.6g) in toluene (7 ml) is added asolution of 2-bromoacetophenone (1.01 equiv) in toluene (16 ml). After a few minutes thecrystallizationofthepyridiniumsaltinitiatesandrefluxingiscontinuedfor3.5h.AftercoolingtoRT,thecolorlesssolidisfiltered,washedwithtoluene(2x15ml),anddriedinvacuo.b)Indolizine:Toavigorouslystirred,warm(80°C)solutionofthepyridiniumsalt(24mmol) inH2O(60ml)isaddedinsmallportionssodiumhydrogencarbonate(3.66equiv).Anintenseyellowcolorisformed,andafterabout1minayellowishsolidstartscrushingout.Stirringiscontinuedfor30minat80°C.AftercoolingtoRT,thesolidisfiltered,washedwithH2O(3x30ml),anddriedinvacuo.Purification:Thesolidisrecrystallized.Findthepropersolventorsolventmixture!Analysis:TLC,meltingpoint,IR.Fillinthesetablesbeforeyoubegintheexperiments:

Reactant MW Equiv Moles Mass Volume Purity2-Methylpyridine 1.00 3.60g Bromoacetophenone 1.01 Product MW Yield Moles Mass MP Note:2-Methylpyridine=2-PicolineReactant MW Equiv Moles Mass Volume PurityPyridiniumsalt 1.00 24mmol Sodiumbicarbonate 3.66 Product MW Yield Moles Mass MP

Student Manual OACP I (2018)

ETHZürich·OACPI 20

6b)3,5-Diphenylisoxazole

Preparation:a)Diketone:Toaboilingsuspensionofsodiumhydride(60%inmineraloil;1.5equiv) inanhydrouscyclohexane (33ml) isdropwiseaddeda solutionof acetophenone (25mmol) andethylbenzoate(2.00 equiv) in cyclohexane (5 ml). Time of addition should be chosen in a way such that thesuspensionisboilingwithoutexternalheating(ca.30min).Aftertheadditioniscomplete,heatingtorefluxiscontinueduntilgasformationhasceased(ca.1h).AftercoolingtoRTamixtureofglacialaceticacid(2.5ml)andH2O(12.5ml)isslowlyadded,andthemixtureispouredintoice-coldwater(12.5ml)andthephasesareseparated.Theaqueousphaseisextractedwithether(2x25ml),andthecombinedorganiclayersarewashedwithH2O(25ml),dried(Na2SO4),filtered,andconcentratedinvacuo.Totheremainingorangeoil isaddedpentanetoinitiatecrystallization.ThecrudesolidisrecrystallizedfromMeOHtoaffordcolorlesscrystals.b) Isoxazole: To a solution of the diketone (10 mmol) in EtOH (20 ml) is added a solution ofhydroxylaminehydrochloride(2equiv)inwater(3ml),and2dropsofconcentratedNaOHisadded.Themixture is heated to reflux for 1 h. After cooling to RT, the formed crystals are collected byfiltration.Purification:Thesolidisrecrystallized.Findthepropersolventorsolventmixture!Analysis:TLC,meltingpoint,IR.Fillinthesetablesbeforeyoubegintheexperiments:

Reactant MW Equiv Moles Mass Volume PurityAcetophenone 1.00 25mmol Ethylbenzoate 2.00 Sodiumhydride 1.50 60%Product MW Yield Moles Mass MP Reactant MW Equiv Moles Mass Volume PurityDiketone 1.00 10mmol NH2OH·HCl 2.00 Product MW Yield Moles Mass MP

6c)O-benzylhydroxylamine

Student Manual OACP I (2018)

ETHZürich·OACPI 21

Preparationa)N-(benzyloxy)phthalimide:N-Hydroxyphthalimide(50mmol)andNa2CO3(1.00equiv)weredissolvedinamixtureofDMF(67mL),acetonitrile(12mL)andwater(67mL).TotheredsolutionBenzylchloride(1.06equiv)wasaddedandthemixturestirredatroomtemperaturefor5hours(orlongerforthepraktikum),duringwhichtimethesolutionlightensfromaredcolourtoorangeoryellow.Asolidprecipitatesout,whichshouldbefiltered,washedwithwater(3x30mL),-20°Ccoldmethanol(2x22mL)anddriedinvacuotoyieldtheN-(benzyloxy)phthalimideasawhitepowder.b)O-Benzylhydroxylamin:N-(benzyloxy)phthalimide(1.00equiv)isdissolvedinCH2CL2(0.3M)andheatedtoca.35°C.Hydrazinmonohydrate(2.00equiv)isaddedandthemixturestirredfor2.5hours.Theresultingsuspensioniscooledtoroomtemperatureandfiltered.(Important:TheproductisNOTthesolid)Thefiltrateiswashedsuccessivelywith2MNaOHandbrine.Itisdried(Na2SO4),filtered,andconcentratedinvacuo.Purification:Thecrudeproduct(oil)isdissolvedinEtOH(30mL)andheated70°C.HClconc.isadded(1.00equiv,~4mL)andthemixturecooledtoroomtemperature.Theproductwillcrystallizeandiscollectedbyfiltration.Theproductwaswashedwithcoldiso-propanol.Analysis:TLC,meltingpoint,IR.Fillinthistablebeforeyoubegintheexperiment:

Reactant MW Equiv Moles Mass Volume PurityN-Hydroxyphthalimide 1.00 50mmol Na2CO3 1.00 Benzylchloride 1.06 Product MW Yield Moles Mass MP Reactant MW Equiv Moles Mass Volume PurityN-(benzyloxy)phthalimide 1.00 -Hydrazinemonohydrate 2.00 -HClconc. 1.00 -Product MW Yield Moles Mass MP

Pleasesubmitthefinalproducttoyourteachingassistant!

Na2CO3

DMF:ACN:H2ON

O

O

OH ClN

O

O

OPh

N2H4 * H2O

CH2Cl2H2N O

Ph*HCl

Student Manual OACP I (2018)

ETHZürich·OACPI 22

Week7:NucleophilicAromaticSubstitution

7a)1-Nitro-4-phenoxybenzene

Preparation:Inathree-neckedround-bottomedflask,equippedwithanadditionfunnel,amagneticstirbar,andacondenser,NaH(60%inmineraloil;1.6equiv)suspendedinDMF(20ml).Stirringisstartedandasolutionofphenol(1.5equiv)inDMF(20ml)isaddeddropwiseatRT.Themixtureisstirred for 1h atRTbefore4-fluoronitrobenzene (10mmol) inDMF (4ml) is addeddropwise. Thereactionmixturemightbecomewarmandturndarkbrownincolor.ThereactionisstirredatRTfor1h,thenat50°Cfor12h.ThenitispouredintosaturatedaqueousNH4ClandextractedwithMTBE(3 ×). The combined ether layers are washed with 0.2M NaOH (until aqueous washes remaincolorless),1MHCl,andsaturatedaqueousNaCl, thendried (MgSO4), filtered,andconcentrated invacuo.Purification:Theresidueispurifiedbyflashcolumnchromatographyorrecrystallization.Analysis:TLC,meltingpoint,IR.Fillinthistablebeforeyoubegintheexperiment:

Reactant MW Equiv Moles Mass Volume Purity4-Fluronitrobenzene 1.00 10mmol Phenol 1.50 Sodiumhydride 1.60 60%Product MW Yield Moles Mass MP

Student Manual OACP I (2018)

ETHZürich·OACPI 23

7b)1-Nitro-4-(3-phenylpropoxy)benzene

Preparation:Inathree-neckedround-bottomedflask,equippedwithanadditionfunnel,amagneticstirbar,andacondenser,NaH(60%inmineraloil;1.6equiv)suspendedinDMF(20ml).Stirringisstartedandasolutionof3-phenylpropanol(1.5equiv)inDMF(20ml)isaddeddropwiseatRT.Themixture is stirred for 1h at RT before 4-fluoronitrobenzene (10mmol) in DMF (4ml) is addeddropwise.Thereactionmixturemightbecomewarmandturndarkbrown incolor.Thereaction isstirred at RT for 1h, then at 50°C for 12h. Then it is poured into saturated aqueous NH4Cl andextracted with MTBE (3 ×). The combined ether layers are washed with 1M HCl, and saturatedaqueousNaCl,thendried(MgSO4),filtered,andconcentratedinvacuo.Purification:Theresidueispurifiedbyflashcolumnchromatographyorrecrystallization.Analysis:TLC,meltingpoint,IR.Fillinthistablebeforeyoubegintheexperiment:

Reactant MW Equiv Moles Mass Volume Purity4-Fluronitrobenzene 1.00 10mmol 3-Phenylpropanol 1.50 Sodiumhydride 1.60 60%Product MW Yield Moles Mass MP

Student Manual OACP I (2018)

ETHZürich·OACPI 24

7c)4-Nitro-1-(1-methylethoxy)benzene

Preparation:Inathree-neckedround-bottomedflask,equippedwithanadditionfunnel,amagneticstirbar,andacondenser,NaH(60%inmineraloil;1.6equiv)issuspendedinDMF(20ml).Stirringisstartedandasolutionof2-Propanol(1.5equiv)inDMF(20ml)isaddeddropwiseatRT.Themixtureisstirredfor1hatRTbefore4-fluoronitrobenzene(10mmol)inDMF(4ml)isaddeddropwise.Thereactionmixturemightbecomewarmandturndarkbrownincolor.ThereactionisstirredatRTfor1h,thenat50°Cfor12h.ThenitispouredintosaturatedaqueousNH4ClandextractedwithMTBE(3×).Thecombinedetherlayersarewashedwith1MHCl,andsaturatedaqueousNaCl,thendried(MgSO4),filtered,andconcentratedinvacuo.Purification:Theresidueispurifiedbyflashcolumnchromatography.Analysis:TLC,meltingpoint,IR.Fillinthistablebeforeyoubegintheexperiment:

Reactant MW Equiv Moles Mass Volume Purity4-Fluronitrobenzene 1.00 10mmol -2-Propanol 1.50 -Sodiumhydride 1.60 - 60%Product MW Yield Moles Mass MP

NO2

FHO

NO2

ONaH

DMF

Student Manual OACP I (2018)

ETHZürich·OACPI 25

Week8:ElectrophilicAdditionstoAlkenes

8a)2-p-Tolyloxirane

Preparation: 4-Methylstyrene (10mmol) is dissolved in CH2Cl2 (50ml) and mixed with an equalamountofwater containingNaHCO3 (5g).To this solution is carefully addedm-CPBA (1.1equiv),andthereactionmixtureisstirredatRTuntilcompletion(followreactionbyTLC,~2.5h).Thenitistreatedwith aqueousNa2SO3 (6.5g in 50ml) for 20min. The phases are then separated, and theaqueousphaseisextractedwithCH2Cl2(2×50ml).ThecombinedorganicphasesarewashedwithaqueousNaHCO3(2×100ml)andwater,thendried(MgSO4),filtered,andconcentratedinvacuo.Purification:Ifnecessary(TLCanalysis),theresidueispurifiedbyflashcolumnchromatography.Analysis:TLC,IR.Fillinthetablebeforeyoubegintheexperiment:

Reactant MW Equiv Moles Mass Volume Purity4-Methylstyrene 1.00 10mmol m-CPBA 1.10 77%Product MW Yield Moles Mass

Student Manual OACP I (2018)

ETHZürich·OACPI 26

8b)2-(4-tert-Butylphenyl)ethanol

Preparation: To a three-necked round-bottomed flask, equipped with an addition funnel, amagnetic stirbar, anda thermometer,dryTHF (20mL) is added followedbyNaBH4 (0.46equiv).Themixture is stirred until a suspension is formed and cooled to -5 to 0°C (NaCl/icemixture). AsolutionofIodine(0.19equiv)indryTHF(10mL)isaddeddropwiseassuch,sothatthebrowncolorof the iodine disappears right after each drop. Afterwards a solution of the alkene (3.21 g, 20.0mmol,1.00equiv) indryTHF (10mL) isaddedas such, so that the internal temperaturedoesnotexceed30°C.Themixtureisallowedtostirforanother2hatroomtemperatureandcooledto0°C.Water(2.6mL)isaddedcarefullyfollowedbyTHF(25mL)anda3MNaOHsolution(40mL).Whilestirring a 30% solution of H2O2 (2.00 equiv) is added dropwise as such, so that the internaltemperature does not exceed 30 °C. The mixture is stirred for another 20 min and poured in aseparatoryfunnelandtheflaskrinsedwithMTBE(10mL).TheaqueousphaseissaturatedwithNaCl(15-20g), thephasesareseparatedandtheaqueousphaseextractedwithMTBE(3x10mL).Thecombined organic phases are washed with brine (2 x 10 mL), dried (K2CO3), filtered andconcentratedinvacuo.Purification:Theresidueispurifiedbyflashcolumnchromatography(EtOAc/hexanes=1/5).Analysis:TLC,IR.Fillinthetablebeforeyoubegintheexperiment:

Reactant MW Equiv Moles Mass Volume Purity4-tert-Butylstyrene 1.00 20.0mmol Sodiumborohydride 9.2mmol Iodine(I2) 3.8mmol Hydrogenperoxide 30%Product MW Yield Moles Mass

Me Me

MeMe Me

Me

OH1) NaBH4, I2

2) H2O2, NaOH

Student Manual OACP I (2018)

ETHZürich·OACPI 27

8c)2-Bromo-1-p-tolylethanol

Preparation:Toasolutionof4-methylstyrene (15mmol) inTHF (30ml) isaddedwater (6ml)andNBS(1.5equiv)atRTandthemixtureisstirreduntilcompletionofthereaction(followreactionbyTLC, ~30min). After completion of the reaction, THF is evaporated and the residue is extractedtwicewithCH2Cl2(15ml).Thecombinedorganiclayersarewashedwithadiluteaqueoussolutionofsodium hypochlorite (Javelwasser), and then with saturated aqueous NaCl, afterwards dried(Na2SO4),filtered,andconcentratedinvacuo.Purification:Theresidueispurifiedbyflashcolumnchromatography.Analysis:TLC,IR.Fillinthetablebeforeyoubegintheexperiment:

Reactant MW Equiv Moles Mass Volume Purity4-Methylstyrene 1.00 15.0mmol N-Bromosuccinimid 1.50 Product MW Yield Moles Mass

Student Manual OACP I (2018)

ETHZürich·OACPI 28

Weeks9-11:Multi-StepSynthesisofLigands

9a)(R)-1,1'-Binaphthyl-2,2'-diol(BINOL)

[Tet.Asymm.2003,14,2763.]

1.PreparationofracemicBINOL

Pleasesubmitthefinalproducttoyourteachingassistant!Day1:2-Naphthol(15.00g,104mmol)andwater(600ml)areheatedunderrefluxina1-lround-bottomedflaskequippedwitha refluxcondenser.A solutionofFeCl3·6H2O (30.00g, 111mmol) inwater (60ml)isaddeddropwisewithvigorousstirringthroughthecondenserandthemixtureisheatedunderreflux for another 30minafter completionof theaddition.Racemic2,2’-dihydroxy-1,1’-binaphthylprecipitatesduringtheprocedureandthehotslurryisfilteredthroughapreheatedBuchnerfunnel.Afterwashingwithboilingwateruntilthefiltratebecomescolorless,thebrownishresidueisdriedbysuckingairthroughthefunnelfor2minutes.Thesolidispreadonasheetofaluminumfoilanddriedovernightontheair.Day2:Tworecrystallizationproceduresareperformedfromrefluxingtoluene(180ml)withcoolingtoRTinan ice-/waterbathandfiltrationthroughafiltrationfunnel.Themother liquorsarecombined,thesolvent removedand the residue recrystallized twice in the same fashion from toluene (2×80ml).Bothsetsofcrystalsarecombinedanddriedundervacuuminthedesiccator(16hat20mbar).Theproductisobtainedascolorlessneedles(11.81g,41.11mmol,79%;mp:219°C,lit218°C).

Student Manual OACP I (2018)

ETHZürich·OACPI 29

2.Resolutionofdiaminocyclohexane

Day3:Ina500mltwo-neckedround-bottomedflaskequippedwithrefluxcondenser,droppingfunnelanda bigmagnetic stir bar, racemic cyclohexanediamine (11.4g, 100mmol) is dissolved in a solventmixtureofwater(20ml)andmethanol(160ml).Thenglacialaceticacid(7.5ml,7.8g,130mmol)isaddeddropwisewithstirring.AsolutionofL-(+)-tartaricacid(7.51g,50.0mmol)inmethanol(30ml)isaddeddropwiseandthedroppingfunnelwasrinsedwithmethanol(10ml).Theoverallproportionofmethanoltowateristherefore10:1.Thesolutionisrefluxedfor24h.Day4:Aftercooling to roomtemperature, theslurry is filtered.Theprecipitate iswashedwithmethanol(3×20ml) and oven-dried (12h at 80°C). Thereby (R,R)-cyclohexanediammonium tartrate isobtainedasanenantiomericallypure,crystallinepowder(12.80g,48.5mmol,49%yield,>99.8%ee[HPLC]).Tothissolidisadded250ml4MNaOH.Themixtureisextracted2x200mlCH2Cl2.DryingoverMgSO4andconcentrationwillprovidethefreeamine(R,R)-cyclohexanediamine.3.ResolutionofracemicBINOL

Day5:Formationof(R)-BINOL-(R,R)-cyclohexanediamine·tolueneinclusioncomplexRacemicBINOL (5.73g, 20.03mmol) is added to a solution of (R,R)-cyclohexanediamine (2.514g,22.05mmol,2.2equiv.)intoluene(60ml)andthesolutionisstirredfor30minatroomtemperature,heated to 100°C for 10min and then slowly cooled to room temperature.A precipitatewill formwhich is filteredandwashedwith cold toluene (2×10ml).Recrystallizationof theprecipitate fromhot toluene (20ml) affords enantiomerically pure (R)-BINOL·(R,R)-cyclohexanediamine·toluene(4.47g, 9.06mmol, 45%, 99.8% ee) as colorless needles which are dried in the desiccator undervacuum(16hat20mbar).4.Liberationof(R)-BINOL

OHOH

OHOH

H2N

H2N

CH3

Student Manual OACP I (2018)

ETHZürich·OACPI 30

Day6:Theinclusioncomplex(R)-BINOL·(R,R)-cyclohexanediamine·toluene(4.47g,9.06mmol)isdissolvedin amixture of water (9ml) andmethanol (80ml) and L-(+)-tartaric acid (1.136g, 9.97mmol, 1.1equiv.)isaddedinoneportion.Thereactionisheatedunderrefluxfor16h.Day7:After cooling theprecipitated (R,R)-cyclohexanediammonium (+)-tartrate is removedby filtration,anddiscarded.Water (30ml) is added to the filtrate and themethanol is removedunder reducedpressureaffordingtheprecipitationofthe(R)-BINOL.Theprecipitateisfiltered,washedwithwater(5×20ml) and transferred into a separatory funnel charged with CH2Cl2 (50ml) and saturatedaqueousNa2CO3solution(20ml).Aftervigorousshaking,theorganiclayerisseparated,driedoverMgSO4 and after solvent removal under reduced pressure (R)-BINOL (2.43g, 8.50mmol, 94%,>99.8%ee)isobtainedinenantiomericallypureform.

Pleasesubmitthefinalproducttoyourteachingassistant!

OHOH

H2N

H2N

CH3 OHOH

Student Manual OACP I (2018)

ETHZürich·OACPI 31

9b)Diphenylbutadien

1.1,2-dibromo-1-phenylethane

Day1

Preparation:Toa250mLroundbottomflask,equippedwithadroppingfunnelandmagneticstirbar, is added 100 mmol styrene in 100 mL cyclohexane. The mixture is stirred for 10 min whilecoolingwith a coldwater bath (8 – 10 °C). Afterwards a solution of 100mmol bromine in 50mLcyclohexane is added dropwise (check dropping funnel for leaking before adding bromine). (Thespeedofadditionshouldbeassuch,sothattheredcolorofthebrominedisappearsrightaftereachdrop).Aftercompleteadditionthemixtureisstirredfor15minatroomtemperature.Theprecipitatedproductisfiltered.Thefiltrateiswashedwithaqueoussodiumthiosulfatesolution,dried over sodium sulfate and concentrated in vacuo to yield a second product fraction. Thecombinedcrudeproductisdriedinvacuo.Day2:

Purification:Thesolidisrecrystallized.Findthepropersolventorsolventmixture!Analysis:TLC,meltingpoint,IR.Fillinthesetablesbeforeyoubegintheexperiments:

Reactant MW Equiv Moles Mass Volume PurityStyrene 1.00 100mmol Bromine 1.00 Product MW Yield Moles Mass MP

C C C C

CH2BrBr2+

Br

Student Manual OACP I (2018)

ETHZürich·OACPI 32

2.Phenylacetylene

Preparation:A250mL roundbottom flask is chargedwith 75mmol 1,2-dibromo-1-phenylethaneandmixedwith350mmol(powdered!)KOH.Theflask isequippedwitharefluxcondenserand24mL EtOH are slowly added through the condenser. An intense reactionwill start and the flask isgentlyshakenfromtimetotimeuntilthereactionhasceased.Afterwardsthemixtureisheatedtorefluxforonehour.Themixture is allowed to cool to room temperature and 100mLwater is added. Themixture isextracted twice with tert-Butylmethylether. The combined organic phases are dried (NaSO4),filtered,andconcentratedinvacuo.Purification:Theresidueisfractionallydistilledunderreducedpressure(bp:142–144°C/1000hPa;40–45°C/17hPa).Thereceivingflasksarecooledwithanicebath.Analysis:TLC,boilingpoint,IR.Fillinthesetablesbeforeyoubegintheexperiments:Reactant MW Equiv Moles Mass Volume Purity1,2-dibromo-1-phenylethane 1.00 75mmol KOH 4.60 Product MW Yield Moles Mass MP

CH2Br

BrEtOH / KOH

Student Manual OACP I (2018)

ETHZürich·OACPI 33

3.Diphenylbutadiene

Preparation:A200mLroundbottomflaskequippedwithalargestirbarischargedwith2.5mmolCuCl, 40 mL acetone and 2.0 mmol TMEDA. 50 mmoL phenylacetylene are added via syringedropwise within five minutes while stirring. Afterwards the reaction is stirred vigorously for twomorehours.Thesolutionisfilteredviafilterpaperandthefiltrateisconcentratedinvacuotoabout15mL.Aftercoolingtheproductcrystallizesand30mLwaterisadded.Themixtureisfilteredandwashedwithwateruntilthewashingwaterisnotblueanymore.Thecrudeproductisdriedanddissolvedin50mLcyclohexane.Thesolutionisfilteredagainviafilterpapertoremovesolidimpuritiesandthesolventremovedunderreducedpressure.Purification:Thesolidisrecrystallized.FindaproperEthanol/H2Omixture!Analysis:TLC,meltingpoint,IR.

Fillinthesetablesbeforeyoubegintheexperiments:

Reactant MW Equiv Moles Mass Volume PurityCuCl 0.05 2.5mmol TMEDA 0.04 2.0mmol Phenylacetylene 1.00 50mmol Product MW Yield Moles Mass MP

C C C CO2 (air)

CuCl / TMEDA

Student Manual OACP I (2018)

ETHZürich·OACPI 34

9c)4-Ethylbenzoicacid

1.4-(Bromomethyl)benzoicacid

Preparation: A 250mL round-bottom flask under nitrogen atmosphere is fittedwith amagneticstirbarandarefluxcondenser.TheflaskischargedwithdryCyclohexane(75mL),4-Methylbenzoicacid(60.0mmol,1.00equiv)andNBS(1.00equiv).TothesolutionaspatulatipofAIBN(~50mg;nometalspatula!)isaddedandthemixtureslowlyheatedtoreflux.Refluxingiscontinuedfor1handcooleddownto0°Cfor1h.TheprecipitateiscollectedbyfiltrationandwashedwithCyclohexane(3x35mL).Purification: To the solid 150 mL water is added and the mixture stirred for 10 min. The non-dissolvedresiduesarecollectedbyfiltration,washedwithice-water(50mL)anddriedinavacuumdesiccatoroversilica.Analysis:TLC,meltingpoint,IR.Fillinthesetablesbeforeyoubegintheexperiments:

Reactant MW Equiv Moles Mass Volume Purity4-Methylbenzoicacid 1.00 60mmol N-Bromosuccinimide 1.00 AIBN 0.005 Product MW Yield Moles Mass MP

COOH

Me

COOH

MeN

O

O

BrAIBN COOH

BrNH

O

O

Student Manual OACP I (2018)

ETHZürich·OACPI 35

2.(4-carboxybenzyl)triphenylphosphoniumbromide

Preparation: A 250mL round-bottom flask under nitrogen atmosphere is fittedwith amagneticstirbar and a reflux condenser. The flask is charged with dry Acetone (150 mL), 4-(Bromomethyl)benzoicacid(20.0mmol,1.00equiv)andPPh3(1.00equiv).Themixtureisheatedtorefluxfor1handallowedtocooldown.Thereactionmixtureisfurthercooledinanicebathandtheprecipitatecollectedbyfiltration.Thefiltrateisconcentratedto50mLandcooledinanicebathfor30min.Another batch of product can be collected by filtration. The combined solids arewashedwithMTBE(2x25mL)anddried.Purification:Thephosphoniumsaltcanbeusedwithoutfurtherpurification.Analysis:TLC,IR.Fillinthesetablesbeforeyoubegintheexperiments:

Reactant MW Equiv Moles Mass Volume Purity4-(Bromomethyl)benzoicacid

1.00 20mmol

Triphenylphospine 1.00 Product MW Yield Moles Mass MP

COOH

Br

COOH

P+PhPh Ph

Br-

PPh3

Student Manual OACP I (2018)

ETHZürich·OACPI 36

3.4-Vinylbenzoicacid

Preparation:A100mLround-bottomflaskisfittedwithamagneticstirbarandadroppingfunnel.(4-carboxybenzyl)triphenylphosphoniumbromide (10mmol, 1.00 equiv) is suspended inwater (15mL)and37%aqFormaldehydesolution(50mL)isadded.Thedroppingfunnelischargedwitha5MNaOHsolution(8.00equiv)(checkdroppingfunnelforleakingbeforeaddingbase),whichisaddedover 30 min with vigorous stirring at room temperature. The mixture is stirred for 1 h at roomtemperature. The precipitate is filtered andwashedwithwater (3 x 25mL). The filtrate (not thesolid!)isacidifiedtopH1bydropwiseadditionofhalfconcentratedHCl.Theprecipitateiscollectedbyfiltration,washedwithice-water(3x5mL)anddriedinadesiccatoroverphosphorouspentoxide.Purification:Theproductcanbeusedwithoutfurtherpurification.Analysis:TLC,IR.Fillinthesetablesbeforeyoubegintheexperiments:

Reactant MW Equiv Moles Mass Volume Purity(4-carboxybenzyl)triphenylphosphoniumbromide

1.00 10mmol

Formaldehyde 50mL 37%NaOH 8.00 - -Product MW Yield Moles Mass MP

COOH

P+PhPh Ph

Br-

CH2O, NaOHCOOH

Student Manual OACP I (2018)

ETHZürich·OACPI 37

4.4-Ethylbenzoicacid

Preparation:A100mLround-bottomflaskfittedwithamagneticstirbarandarefluxcondenserischargedwith4-Vinylbenzoicacid(5.0mmol,1.00equiv)anddissolvedinEtOH(50mL).Ammoniumformate(10.0equiv)isaddedfollowedbyPd/C(10wt%ofsubstrate).Themixtureisheatedcarefullyto reflux for1h.Aftercooling to roomtemperature themixture is fitered throughasmallplugofCelite,whichiswashedwithEtOH.Thesolventisremovedandwater(40mL)isadded.TheaqueousphaseisextractedwithMTBE(3x30mL).Thecombinedorganiclayersaredried(Na2SO4),filtered,andconcentratedinvacuo.Purification:Thesolidisrecrystallized.FindaproperEthanol/H2Omixture!Analysis:TLC,IR.Fillinthesetablesbeforeyoubegintheexperiments:

Reactant MW Equiv Moles Mass Volume Purity4-Vinylbenzoicacid 1.00 5.0mmol Pd/C10% - - 74mg - 10%Ammoniumformate 10.0 Product MW Yield Moles Mass MP

Pd/C, HCO2NH4COOH

Me

COOH