2021
Organische Chemie II
BA2 BIOCHEMIE & BIOTECHNOLOGIE
TESSA NUYTTENS
Contents
Hoofdstuk 1: herhaling .................................................................................................................................. 5
Reacties van alkenen .................................................................................................................................. 5
Substitutie en eliminatiereacties ............................................................................................................... 6
Reacties van alkynen .................................................................................................................................. 6
Grignard reagens ........................................................................................................................................ 6
Reacties van alcoholen ............................................................................................................................... 7
Reacties van ethers en epoxiden ............................................................................................................... 7
Hoofdstuk 2: carbonyl verbindingen I .......................................................................................................... 8
Nomenclatuur ............................................................................................................................................. 8
Structuur ..................................................................................................................................................... 9
Reactiviteit .................................................................................................................................................. 9
Substitutie-mechanisme .......................................................................................................................... 10
Reacties op zuurhalogeniden ................................................................................................................... 10
Reacties van zuuranhydriden ................................................................................................................... 11
Reacties van esters .................................................................................................................................... 11
Zure hydrolyse ....................................................................................................................................... 11
Alcoholyse (transesterficatie) .............................................................................................................. 12
Aminolyse van een ester ....................................................................................................................... 12
Alkalische hydrolyse ............................................................................................................................. 13
Triglyceriden en oliën .............................................................................................................................. 13
Reacties van carbonzuren ........................................................................................................................ 14
Fischer verestering ............................................................................................................................... 14
Synthese van zuuranhydriden ............................................................................................................. 14
Synthese van zuurhalogeniden ............................................................................................................ 15
Amide uit een carbonzuur .................................................................................................................... 15
Reacties van amiden ................................................................................................................................ 15
Verklaring onreactiviteit van amiden...................................................................................................... 16
β-Lactams ................................................................................................................................................. 16
Proteïnen .................................................................................................................................................. 16
,1 Organische Chemie II
α-aminozuren ........................................................................................................................................... 17
Reacties van nitrillen................................................................................................................................ 18
Zure (katalyse) hydrolyse ..................................................................................................................... 18
Basische hydrolyse ............................................................................................................................... 18
Hoofdstuk 3: carbonyl verbindingen II ...................................................................................................... 18
Naamgeving .............................................................................................................................................. 18
Natuurlijk voorkomende aldehyden en ketonen .................................................................................... 19
Relatieve reactiviteit t.o.v. nucleofielen .................................................................................................. 19
Reacties van klasse II carbonylverbindingen .........................................................................................20
RLi en RMgX reactantia ..........................................................................................................................20
Acetylide ionen ......................................................................................................................................... 23
Hydrogen cyanide (vorming cyanohydrins) ........................................................................................... 23
Reacties met een hydride ion ................................................................................................................... 24
Reacties van aldehyden en ketonen met stikstof nucleofielen ............................................................. 28
Aminen ..................................................................................................................................................28
Hydroxylamine, hydrazine en semicarbazide ..................................................................................... 29
Reacties van aldehyden en ketonen met zuurstof nucleofielen ............................................................30
Water geeft hydraten ............................................................................................................................30
Alcoholen geven hemiacetalen, acetalen, hemiketalen en ketalen .................................................... 31
Koolhydraten of sacchariden ............................................................................................................... 32
Reacties van aldehyden en ketonen met zwavel nucleofielen................................................................ 34
Reacties van aldehyden en ketonen met fosforylide .............................................................................. 36
Reacties van α,β-onverzadigde aldehyden en ketonen .......................................................................... 39
Hoofdstuk 4: carbonylverbinding III .......................................................................................................... 41
Zure gekatalyseerde halogenering ........................................................................................................... 42
Halogenering onder basische omstandigheden ..................................................................................... 42
Hell-Volhard-Zellinsky reactie ................................................................................................................ 43
Alkylering van het α-C-atoom ................................................................................................................. 43
Akylering ................................................................................................................................................... 44
Acylering ................................................................................................................................................... 44
Enolaten met α,β-gesubstitueerde carbonyl verbindingen.................................................................... 45
Aldolcondensatie ...................................................................................................................................... 45
Claisencondensatie ................................................................................................................................... 46
Intramoleculaire condensaties en addities ............................................................................................. 47
Intramoleculaire Claisen condensatie ................................................................................................. 47
Intramoleculaire Aldol condensatie ....................................................................................................48
Decarboxylering van β-ketocarbonzuren ................................................................................................48
Malonzuurester synthese ......................................................................................................................... 49
,2 Organische Chemie II
Acetoacetaatester synthese ...................................................................................................................... 49
Enolaten en enolaatequivalenten ............................................................................................................ 50
Keton-enolaten ..................................................................................................................................... 50
Aldehyde-enolaten................................................................................................................................ 51
Aldolcondensatie met specifiek enol equivalenten ............................................................................. 51
Hoofdstuk 5: aromatische verbindingen .................................................................................................... 52
Naamgeving .............................................................................................................................................. 52
Reactiviteit van benzene .......................................................................................................................... 53
Elektrofiele aromatische substitutiereacties........................................................................................... 53
Halogenering ........................................................................................................................................ 53
Friedel-Crafts acylering (RCO) ............................................................................................................ 54
Friedel-Crafts alkylering (CH3CO) ...................................................................................................... 55
Nitrering................................................................................................................................................ 55
Sulfonylering ......................................................................................................................................... 56
Desulfonylering .................................................................................................................................... 56
Sulfonylering-desulfonylering ............................................................................................................. 56
Substituenten op de benzene ring ........................................................................................................... 56
Alkyl substituent ................................................................................................................................... 56
NO2 substituent .................................................................................................................................... 57
C=C, C=O of C≡N substituenten .......................................................................................................... 58
Effect van de substituenten op de reactiviteit......................................................................................... 58
Relatieve reactiviteit van gesubstitueerde benzenen ............................................................................. 59
Effect van de substituenten op de oriëntatie .......................................................................................... 59
Belangrijke aspecten ivm elektrofiele aromatische substitutie ............................................................. 61
Geen Lewis-zuur katalysator bij sterk activerende substituenten ..................................................... 61
Geen Friedel-Crafts bij meta richters.................................................................................................. 61
Geen Friedel-Crafts bij (N-gesubstitueerde) anilinen ........................................................................ 62
Geen nitratie van aniline ...................................................................................................................... 62
Effect van de substituenten op de pKa ................................................................................................ 63
Synthese van trigesubstitueerde benzenen ............................................................................................. 63
Beide substituenten richten op dezelfde plaats .................................................................................. 63
Beide richten op een verschillende plaats ........................................................................................... 63
Elektrofiele aromatische substitutie op naphthalene ............................................................................ 64
Elektrofiele aromatische substitutie op monogesubtitueerde naphthalene ......................................... 65
Reactiviteit van anthracene en phenanthrene ........................................................................................ 66
Synthese van gesubstitueerde benzenen via benzeendiazonium .......................................................... 66
SN1 reactie via Ar+ ................................................................................................................................. 66
Sandmeyer reactie via Ar...................................................................................................................... 66
, 3 Organische Chemie II
Nucleofiele substitutie op aromaten .......................................................................................................68
Hoofdstuk 6: oxidatie-reductie reacties ..................................................................................................... 70
Oxidatie vs reductie .................................................................................................................................. 70
Reductiereacties ....................................................................................................................................... 70
Katalytische hydrogenatie .................................................................................................................... 70
Alkyne reduceren tot trans-alkene ...................................................................................................... 71
Reductie via additie van een hydride ion en een proton .................................................................... 71
Oxidatiereacties ........................................................................................................................................ 73
Alcoholen .............................................................................................................................................. 73
Aldehyden en ketonen .......................................................................................................................... 76
Alkenen ................................................................................................................................................. 77
Akynen .................................................................................................................................................. 81
Oxidatie van hydrochinonen en reductie van chinonen ........................................................................82
Hoofdstuk 7: aminen ...................................................................................................................................82
Nomenclatuur ...........................................................................................................................................82
Eigenschappen van aminen ..................................................................................................................... 83
Synthese van aminen ............................................................................................................................... 83
Synthese van secundaire en tertiaire aminen .........................................................................................84
Reacties van aminen ................................................................................................................................84
Alkylerings reactie ................................................................................................................................84
Amide vorming ..................................................................................................................................... 85
Imine vorming ...................................................................................................................................... 85
Michael additie ..................................................................................................................................... 85
Diazotatie primaire aminen ................................................................................................................. 85
Reacties van kwaternaire ammoniumzouten ......................................................................................... 85
Beckmann omlegging ...............................................................................................................................86
Hofmann omlegging................................................................................................................................. 87
Andere stikstof gebasseerde functionele groepen .................................................................................. 87
H8: diënen .................................................................................................................................................... 87
Nomenclatuur ........................................................................................................................................... 87
Relatieve stabiliteit van diënen .............................................................................................................. 88
Reacties van diënen ................................................................................................................................. 88
Elektrofiele additie op geïsoleerde diënen ......................................................................................... 88
Elektrofiele additie op geconjugeerde diënen .....................................................................................89
Diels-Alder reactie ................................................................................................................................90
H9: radicalen ................................................................................................................................................ 93
Vorming van radicalen ............................................................................................................................. 93
Stabiliteit van koolstofradicalen .............................................................................................................. 93
Organische Chemie II
BA2 BIOCHEMIE & BIOTECHNOLOGIE
TESSA NUYTTENS
Contents
Hoofdstuk 1: herhaling .................................................................................................................................. 5
Reacties van alkenen .................................................................................................................................. 5
Substitutie en eliminatiereacties ............................................................................................................... 6
Reacties van alkynen .................................................................................................................................. 6
Grignard reagens ........................................................................................................................................ 6
Reacties van alcoholen ............................................................................................................................... 7
Reacties van ethers en epoxiden ............................................................................................................... 7
Hoofdstuk 2: carbonyl verbindingen I .......................................................................................................... 8
Nomenclatuur ............................................................................................................................................. 8
Structuur ..................................................................................................................................................... 9
Reactiviteit .................................................................................................................................................. 9
Substitutie-mechanisme .......................................................................................................................... 10
Reacties op zuurhalogeniden ................................................................................................................... 10
Reacties van zuuranhydriden ................................................................................................................... 11
Reacties van esters .................................................................................................................................... 11
Zure hydrolyse ....................................................................................................................................... 11
Alcoholyse (transesterficatie) .............................................................................................................. 12
Aminolyse van een ester ....................................................................................................................... 12
Alkalische hydrolyse ............................................................................................................................. 13
Triglyceriden en oliën .............................................................................................................................. 13
Reacties van carbonzuren ........................................................................................................................ 14
Fischer verestering ............................................................................................................................... 14
Synthese van zuuranhydriden ............................................................................................................. 14
Synthese van zuurhalogeniden ............................................................................................................ 15
Amide uit een carbonzuur .................................................................................................................... 15
Reacties van amiden ................................................................................................................................ 15
Verklaring onreactiviteit van amiden...................................................................................................... 16
β-Lactams ................................................................................................................................................. 16
Proteïnen .................................................................................................................................................. 16
,1 Organische Chemie II
α-aminozuren ........................................................................................................................................... 17
Reacties van nitrillen................................................................................................................................ 18
Zure (katalyse) hydrolyse ..................................................................................................................... 18
Basische hydrolyse ............................................................................................................................... 18
Hoofdstuk 3: carbonyl verbindingen II ...................................................................................................... 18
Naamgeving .............................................................................................................................................. 18
Natuurlijk voorkomende aldehyden en ketonen .................................................................................... 19
Relatieve reactiviteit t.o.v. nucleofielen .................................................................................................. 19
Reacties van klasse II carbonylverbindingen .........................................................................................20
RLi en RMgX reactantia ..........................................................................................................................20
Acetylide ionen ......................................................................................................................................... 23
Hydrogen cyanide (vorming cyanohydrins) ........................................................................................... 23
Reacties met een hydride ion ................................................................................................................... 24
Reacties van aldehyden en ketonen met stikstof nucleofielen ............................................................. 28
Aminen ..................................................................................................................................................28
Hydroxylamine, hydrazine en semicarbazide ..................................................................................... 29
Reacties van aldehyden en ketonen met zuurstof nucleofielen ............................................................30
Water geeft hydraten ............................................................................................................................30
Alcoholen geven hemiacetalen, acetalen, hemiketalen en ketalen .................................................... 31
Koolhydraten of sacchariden ............................................................................................................... 32
Reacties van aldehyden en ketonen met zwavel nucleofielen................................................................ 34
Reacties van aldehyden en ketonen met fosforylide .............................................................................. 36
Reacties van α,β-onverzadigde aldehyden en ketonen .......................................................................... 39
Hoofdstuk 4: carbonylverbinding III .......................................................................................................... 41
Zure gekatalyseerde halogenering ........................................................................................................... 42
Halogenering onder basische omstandigheden ..................................................................................... 42
Hell-Volhard-Zellinsky reactie ................................................................................................................ 43
Alkylering van het α-C-atoom ................................................................................................................. 43
Akylering ................................................................................................................................................... 44
Acylering ................................................................................................................................................... 44
Enolaten met α,β-gesubstitueerde carbonyl verbindingen.................................................................... 45
Aldolcondensatie ...................................................................................................................................... 45
Claisencondensatie ................................................................................................................................... 46
Intramoleculaire condensaties en addities ............................................................................................. 47
Intramoleculaire Claisen condensatie ................................................................................................. 47
Intramoleculaire Aldol condensatie ....................................................................................................48
Decarboxylering van β-ketocarbonzuren ................................................................................................48
Malonzuurester synthese ......................................................................................................................... 49
,2 Organische Chemie II
Acetoacetaatester synthese ...................................................................................................................... 49
Enolaten en enolaatequivalenten ............................................................................................................ 50
Keton-enolaten ..................................................................................................................................... 50
Aldehyde-enolaten................................................................................................................................ 51
Aldolcondensatie met specifiek enol equivalenten ............................................................................. 51
Hoofdstuk 5: aromatische verbindingen .................................................................................................... 52
Naamgeving .............................................................................................................................................. 52
Reactiviteit van benzene .......................................................................................................................... 53
Elektrofiele aromatische substitutiereacties........................................................................................... 53
Halogenering ........................................................................................................................................ 53
Friedel-Crafts acylering (RCO) ............................................................................................................ 54
Friedel-Crafts alkylering (CH3CO) ...................................................................................................... 55
Nitrering................................................................................................................................................ 55
Sulfonylering ......................................................................................................................................... 56
Desulfonylering .................................................................................................................................... 56
Sulfonylering-desulfonylering ............................................................................................................. 56
Substituenten op de benzene ring ........................................................................................................... 56
Alkyl substituent ................................................................................................................................... 56
NO2 substituent .................................................................................................................................... 57
C=C, C=O of C≡N substituenten .......................................................................................................... 58
Effect van de substituenten op de reactiviteit......................................................................................... 58
Relatieve reactiviteit van gesubstitueerde benzenen ............................................................................. 59
Effect van de substituenten op de oriëntatie .......................................................................................... 59
Belangrijke aspecten ivm elektrofiele aromatische substitutie ............................................................. 61
Geen Lewis-zuur katalysator bij sterk activerende substituenten ..................................................... 61
Geen Friedel-Crafts bij meta richters.................................................................................................. 61
Geen Friedel-Crafts bij (N-gesubstitueerde) anilinen ........................................................................ 62
Geen nitratie van aniline ...................................................................................................................... 62
Effect van de substituenten op de pKa ................................................................................................ 63
Synthese van trigesubstitueerde benzenen ............................................................................................. 63
Beide substituenten richten op dezelfde plaats .................................................................................. 63
Beide richten op een verschillende plaats ........................................................................................... 63
Elektrofiele aromatische substitutie op naphthalene ............................................................................ 64
Elektrofiele aromatische substitutie op monogesubtitueerde naphthalene ......................................... 65
Reactiviteit van anthracene en phenanthrene ........................................................................................ 66
Synthese van gesubstitueerde benzenen via benzeendiazonium .......................................................... 66
SN1 reactie via Ar+ ................................................................................................................................. 66
Sandmeyer reactie via Ar...................................................................................................................... 66
, 3 Organische Chemie II
Nucleofiele substitutie op aromaten .......................................................................................................68
Hoofdstuk 6: oxidatie-reductie reacties ..................................................................................................... 70
Oxidatie vs reductie .................................................................................................................................. 70
Reductiereacties ....................................................................................................................................... 70
Katalytische hydrogenatie .................................................................................................................... 70
Alkyne reduceren tot trans-alkene ...................................................................................................... 71
Reductie via additie van een hydride ion en een proton .................................................................... 71
Oxidatiereacties ........................................................................................................................................ 73
Alcoholen .............................................................................................................................................. 73
Aldehyden en ketonen .......................................................................................................................... 76
Alkenen ................................................................................................................................................. 77
Akynen .................................................................................................................................................. 81
Oxidatie van hydrochinonen en reductie van chinonen ........................................................................82
Hoofdstuk 7: aminen ...................................................................................................................................82
Nomenclatuur ...........................................................................................................................................82
Eigenschappen van aminen ..................................................................................................................... 83
Synthese van aminen ............................................................................................................................... 83
Synthese van secundaire en tertiaire aminen .........................................................................................84
Reacties van aminen ................................................................................................................................84
Alkylerings reactie ................................................................................................................................84
Amide vorming ..................................................................................................................................... 85
Imine vorming ...................................................................................................................................... 85
Michael additie ..................................................................................................................................... 85
Diazotatie primaire aminen ................................................................................................................. 85
Reacties van kwaternaire ammoniumzouten ......................................................................................... 85
Beckmann omlegging ...............................................................................................................................86
Hofmann omlegging................................................................................................................................. 87
Andere stikstof gebasseerde functionele groepen .................................................................................. 87
H8: diënen .................................................................................................................................................... 87
Nomenclatuur ........................................................................................................................................... 87
Relatieve stabiliteit van diënen .............................................................................................................. 88
Reacties van diënen ................................................................................................................................. 88
Elektrofiele additie op geïsoleerde diënen ......................................................................................... 88
Elektrofiele additie op geconjugeerde diënen .....................................................................................89
Diels-Alder reactie ................................................................................................................................90
H9: radicalen ................................................................................................................................................ 93
Vorming van radicalen ............................................................................................................................. 93
Stabiliteit van koolstofradicalen .............................................................................................................. 93
