Compendio Reacciones Organicas.pdf
Transcript of Compendio Reacciones Organicas.pdf
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A REVIEW OF ORGANIC REACTIONS
AND REAGENTS
FOR CHEMISTRY 551
January 2002
Dr. B.A. Keay Department of Chemistry
University of Calgary [email protected]
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The following schemes illustrate most of the reactions you were taught in Chemistry 351/353, 354 and/or 451/453. To do well in Chemistry 551 you need to know these reactions and the reagents necessary to effect various chemical reactions. This list is only a guide. You should consult textbooks and reference books for further information on each of these reactions. Links are provided for each entry. Table of Contents Chem 351/353 and 354 Reactions Page Preparation of Alkanes 3 Reactions of Alkanes 3 Preparation of Alkyl Halides 4 Reactions of Alkyl Halides 5 Preparation of Alcohols 6 Reactions of Alcohols 8 Preparation of Ethers 9 Preparation of Alkenes 10 Reactions of Alkenes 10 Preparation of Alkynes 13 Reactions of Alkynes 13 Preparation of Epoxides 14 Reactions of Epoxides 14 Preparation of Aldehydes 15 Preparation of Ketones 16 Reactions of Aldehydes and Ketones 16 Preparation of Carboxylic Acids 20 Reactions of Carboxylic Acids 21 Preparation of Acid Halides and Anhydrides 22 Reactions of Acid Halides and Anhydrides 22 Preparation of Esters 23 Reactions of Esters 23 Preparation of Amides 24 Reactions of Amides 24 Preparation of Lactones 25 Reactions of Lactones 25 Reactions Involving Carbanions 25 Preparation of Amines 28 Reactions of Amines 29 Reactions of Benzene 30 Reactions of Diazonium Salts 31 Changing Directing Ability of Groups on Benzene Rings 32 Diels-Alder Reactions 33 Chem 451/453 Reactions Pericyclic Reactions (Cope, Claisen, Oxy-Cope, etc.) 34 Other Sigmatropic Rearrangements 35 Dipolar Cycloadditons 36 Other Photochemical Reactions 37 Rearrangements 37
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PREPARATION OF ALKANES 1. Hydrogenation of alkenes
H2
Pd, Pt, or Ni 2. Reduction of alkyl halides
a. Hydrolysis of Grignard reagent
R X R Mg X R H
X=Cl, Br, I
Mg
ether
H2O
(b) Reduction by metal and acid
R X R H
X=Cl, Br, I
Zn
HCl
3. Coupling of alkyl halides with organometallic compounds
R X R Li R CuLiR
R' X
R R'
X=Br or I
Li
may be 1o, 2o or 3o
CuI
should be 1o
REACTIONS OF ALKANES 1. Halogenation
R H R X
H
+ X2
hυ
Reactivity: X2: Cl2 > Br2
H: 3o > 2o > 1o > CH3
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PREPARATION OF ALKYL HALIDES 1. From Alcohols
R OH R XHX or PX3
X=Cl, Br or I
2. Halogenation of certain hydrocarbons
R H R X
H
+ X2
hυ
Reactivity: X2: Cl2 > Br2
H: 3o > 2o > 1o > CH3 3. Addition of hydrogen halides to alkenes.
C11
C12
H XC16
C17
HX
X=Cl or Br
H usually attaches to least subsituted carbon atom in double bond (Markovnikovaddition) 4. Addition of halogens to alkenes or alkynes.
C CX X
C C C C C CX
X
X
XX=Cl or Br
X2
trans-addition across double bondsin rings
2 X2
5. Halide exchange
R X R I+ NaI (or NaBr)
X=Cl or Br1o >> 2o
(or Br)acetone
+ NaCl
NaCl ppt's fromacetone and drivethe reaction to completion
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REACTIONS OF ALKYL HALIDES 1. Nucleophilic Substitution
R X R z
R X
R OH
R OH
R OR
R R'-C R'
R R'
R I
R CN
R COOR'
R NH2
R NHR'
R NR'R"
R PPh3
R X Ar R
OO
R R
OO
R RR'
O OR'
+ Z:
+ HO- alcohol
+ H2O alcohol
+ RO- ether(Williamsonether synthesis)
+ alkyne
+ R'-M alkane coupling
M=Li or Mg
+ I- alkyl iodide
+ nitrile-CN
+ R'COO- ester
+ primary amineNH3
+ secondary amineNH2R'
+ tetiary amineNHR'R"
+ phosphonium salt(for Wittig reaction)
PPh3
+
+ ArHAlCl3 Friedel-Crafts reaction
3o halide is best otherwise carbocation rearrangements can occur
R=alkyl and/or OR
-
R'-Xalkylation of 1,3-dicarbonyl systems
R'-Xalkylation of ketone enolates
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2. Dehydrohalogenation: Elimination
C CH X
C Cbase
3. Preparation of Grignard reagent
R-X + Mgether
R-Mg-X 4. Reduction
R-HR-X + M + H+ + M+ + X-
M=Mg, Na, Zn
e.g. Mg followed by water, Na/EtOH, Zn/HCl, PREPARATION OF ALCOHOLS 1. Oxymercuration-demercuration
C11
C12
HO HgOAcC16
C17
C27
C28
HO H+ Hg(OAc)2
H2O NaBH4
Markovnikov addition 2. Hydroboration-Oxidation
C11
C12
H BR2
C16
C17
C27
C28
H OH+
anti-Markovnikov addition
B2H6
diborane
H2O2
3 x
3. Grignard synthesis
O OMgXR
OHR
etherR-Mg-X+
H2O
ketones or aldehydes 4. Hydrolysis of alkyl halides R-X + -OH R-OH + X-
usually requires a silver salt so can bevery expensive
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5. Aldol condensation
H
OR
H
OR
OHR
H
OR
R
base
3-hydroxyaldehydemay eliminate uponworkup
-usually restricted to a condensation between the same aldehyde-crossed Aldol reactions provide complex mixtures of products
2 x
6. Reduction of ketones and aldehydes
R
H
OH
ROH
H
R
R'
OR'
ROH
H
1) H-
2) acid workup
1) H-
2) acid workup
1o alcohols
2o alcohols
aldehydes
ketones
-many sources of hydride-most common are: NaBH4, LiAlH4, DIBAL-H 7. Reductions of acids and esters
R
OH
OH
ROH
H
R
R'O
OH
ROH
H
1) LiAlH4
2) acid workup
1) LiAlH4
2) acid workup
1o alcohols
1o alcohols
+ R'-OH
esters
-NaBH4 will not reduce acids and esters-reductions with LiAlH4 cannot be stopped at the aldehyde
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8. Hydroxylation of alkenes
C CHO OH
C C
C CO
C CHO OH
O
O
OH
Cl
+KMnO4 orNaIO4
cis-addition
MCPBA
epoxide
H2O
H+
anti-addition
MCPBA = meta-chloroperoxybenzoic acid
9. Hydrolysis of Esters
R OR'
O
R OH
OOH
R'+
H3O+ or
NaOH, H2O 10. Misc.
C CX OH
C C +
anti-addition
X2, H2O
X=Cl, Br or I
REACTIONS OF ALCOHOLS 1. Reaction with hydrogen halides
R OH R X
R OH R OTs R X
+ HX
reactivityof HX: HI > HBr > HCl
reactivity of ROH: allyl, benzyl > 3o > 2o > 1o
-poor yielding, rearrangements and eliminationscan occur
BETTER IS:
+ TsClpyridine NaX
X=Cl, Br or I1o alcohol is best
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2. Reaction with phosphorus trihalides
R OH R X+ PX3
X= Br or I 3. Dehydration
C CH OH
C Cacid
3o > 2o > 1o
rearrangements may occur
4. Reactions as acids: reaction with active metals.
R OH R OM+ M
M = Na, K, Mg, Al, etc.
Reactivity: MeOH > 1o > 2o > 3o
5. Ester formation
R OH R' OH
O
R' OR
O+
H+
6. Oxidation
OHR
HH
RH
O
ROH
OOH
RH
H
RR'
OOH
RH
R'
OHR
R"R'
PDC
aldehyde
carboxylic acid
KMnO4
or Swernoxidation
ketone
KMnO4
KMnO4no reaction
or K2Cr2O7
PREPARATION OF ETHERS 1. Williamson Synthesis
R X R OR+ RO-
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PREPARATION OF ALKENES 1. Dehydrohalogenation of alkyl halides
C CX X
C C
X=Cl, Br or I
Zn
2. Reduction of Alkynes
C CR RR R
HHC CR R
R H
RH
H2
Lindlar catalyst
Na or Li
NH3
REACTIONS OF ALKENES 1. Addition of hydrogen. Catalytic hydrogenation
C C C CHH
H2
Pt. Pd, or Ni
syn addition 2. Addition of halogens
C C C CXX
X2
anti additionX=Cl or Br 3. Addition of hydrogen halides
H X
Br
Br
HX
X=Cl or Br
HBr
no peroxides
HBr
with peroxides
Markovnikovaddition
E.g.
anti-Markovnikovaddition
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4. Addition of Water
H OH
H2O
H+
Markovnikov addition 5. Halohydrin formation
C CX OH
C C +
anti-addition
X2, H2O
X=Cl, Br or I
6. Oxymercuration-demercuration
C11
C12
HO HgOAcC16
C17
C27
C28
HO H+ Hg(OAc)2
H2O NaBH4
Markovnikov addition 7. Hydroboration-Oxidation
C CH BR2
C C C CH OH
+
anti-Markovnikov addition
B2H6
diborane
H2O2
3 x
8. Addition of carbenes
C C + ":CH2"
HCCl3 + NaOH :CCl2
dichlorocarbene(neutral electron defficientspecies-very reactive)
E.g.formed "in situ"
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9. Epoxidation
C C C CO
O
O
OH
Cl
MCPBA
epoxide
MCPBA = meta-chloroperoxybenzoic acid
10. Hydroxylation
C CHO OH
C C +KMnO4 orNaIO4
cis-addition 11. Polymerization -not useful in synthesis 12. Allylic Halogenation
C CH C CBr N OO
Br
low conc.
NBSNBS=N-bromosuccinimide=
13. Ozonolysis
C CO O
OO O
O OOH
+ O3
ozonide
Me2S
orZn
+
aldehydes and ketones
reductive workup
H2O2 oxidative workup
+
ketones andcarboxylic acids
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PREPARATION OF ALKYNES 1. Dehydrohalogenation of alkyl dihalides
XX
H
X
X2
anti additionX=Cl or Br
KOH NaNH2
2. Reaction of metal acetylides with primary alkyl halides
H C RNaNH2
Na+RX
R must be primaryX = Br or I
REACTIONS OF ALKYNES 1. Addition of hydrogen
C CR RR R
HHC CR R
R H
RH
R R
HH HH
H2
Lindlar catalyst
Na or Li
NH3
H2H2
Pd, Pt or Ni Pd, Pt or Ni
2 x H2
Pd, Pt or Ni 2. Addition of halogens
C CR RR X
RX
R R
XX XX
X2 X2
X2 = Cl2 or Br2 3. Addition of hydrogen halides
C CR RR X
RH
R R
XH HXHX HX
HX = HCl, HBr, HI
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4. Addition of water
C CR RR OH
RH
R O
RH+ H2O
H2SO4
HgSO4
enol tautomerizes to ketone immediately 5. Formation of metal acetylides
H C NaNH2
Na+
PREPARATION OF EPOXIDES 1. From alkenes
C16
C17
C27
C28O
O
O
OH
ClO O
O
epoxide
MCPBA = meta-chloroperoxybenzoic acid
MCPBA
H2O2
NaOH
-only with conjugated enones, i.e. electron poor double bonds
-the more electron rich the double bondthe better the yield
2. From halohydrins
C CX OH
C C CCO
+
anti-addition
X2, H2O
X=Cl, Br or I
NaOH
X and OH must beanti-periplanar for epoxide to form
REACTIONS OF EPOXIDES 1. Acid-catalyzed opening
C11
C12OH
ZC
12C
11 OC
38C
39 OH
H+ Z:
+
anti-opening
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2. Base opening
C COH
ZCC
O
anti-opening
Z:- +
Z:- can be: RO-, RS-, R2NH, etc. 3. Reaction with Grignard reagents
C COH
RCC
O
anti-opening
+R-Mg-XH+ workup
PREPARATION OF ALDEHYDES 1. Oxidation of primary alcohols
OHR
HH
RH
O
PDC
aldehyde
or Swernoxidation
2. Oxidation of methylbenzenes
HH
H HO
XH
X
benzaldehyde
Cl2, heat
orBr2, benzoylperoxide
water
3. Reduction of acid chlorides
RH
O
R
Cl O
aldehydeacid chloride
LiAlH(OBu-t)3
4. Reimer-Tiemann reaction
OH OH
H
OCHCl3, NaOH
70 oC
-must have a phenol and aldehyde is always introduced into the ortho position to the hydroxygroup
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PREPARATION OF KETONES 1. Oxidation of secondary alcohols
RR'
OOH
RH
R'ketone
KMnO4
or K2Cr2O7
2. Friedel-Crafts acylation
RCl
O
RAr
O+AlCl3
Ar-H
3. Reaction of acid chlorides with organocopper compounds
R'Cl
O R'R
OR-Li
CuXR2CuLi
4. Ethyl acetoacetate synthesis
CH3EtO
O
CH3EtO
O
O
OEt
O
+1. NaOMe, MeOH
2. 10% HCl workup ethyl acetoacetate REACTIONS OF ALDEHYDES AND KETONES 1. Oxidation
R
O
Ar
O
R-CHO or Ar-CHOKMnO4 or
K2Cr2O7
R-CO2H or Ar-CO2H
Aldehydes
Methyl Ketones-haloform reaction
orKOCl
acidic workup
R-CO2H or Ar-CO2H + CHCl3
acidic workup
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2. Reduction to alcohols
R R'
O
Ar R'
O
R R'
OH
Ar R'
OH
R-CHO or Ar-CHO R-CH2OH or Ar-CH2OH
Aldehydes
Ketones
or
acidic workup
NaBH4, MeOH
or LiAlH4
NaBH4, MeOH
or LiAlH4
or
3. Reduction to hydrocarbons
Ar R'
O
Ar R'Ar H
O
Ar H
R R'
O
R R'
or orZn(Hg)
conc. HCl
Clemmensen reduction-must be an aromatic aldehyde or ketone
H2NNH2
NaOH, heat
Wolff-Kishner reduction 4. Reductive amination
R R'
O
R R'
NHRH2NR
NaCNBH3
pH 5 5. Addition of cyanide
R R'
O
R R'
HO CN+ -CN
H+
cyanohydrin
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6. Addition of derivatives of ammonia
R R'
O
R R'
HO NHG
R R'
NG
NOH
NNH2
NNHAr
NNHCONH2
NR
+ H2N-G
H2N-G Product
H2N-OH oxime
H2N-NH2 hydrazone
H2N-NHAr phenylhydrazone
H2N-NHCONH2 semicarbazone
H2N-R imine
7. Addition of alcohols
R R'
O
R R'
R"O OR"+
H+
acetal or ketal
2 R"OH
aldehyde or ketone 8. Addition of Grignard reagents
R R'
O
R R'
HO R"+
H+ workupR"-Mg-X
9. Halogenation of ketones
R
O
H
R
O
X
H+ workup+ X2
X2 = Cl2, Br2, or I2 10. Addition of carbanions a) Aldol condensation
CH3H
O
CH3
HO H
O
+1% HCl
or -OH
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b) Reactions related to aldol condensation O O
Ar+ Ar-CHONaOH
c) Alkylation of Ketones
O O
O
ONH
N N
O
1) LDA, -78oC, THF
2) MeI
1) KOtBu, HOtBu
2) MeI
Enamine Formation Followed by Alkylation
MeI
enamine
H3O+
20
d) Wittig reaction
R' H
O
R' H
R H
R' H
O O
R' H
H R
O HH
+ Ph3P=CHR
Ph3P+-CH2RX-
phosphonium salt
n-BuLi
X-CH2R + Ph3P
mainly Z-isomernonstabilized ylid
EtO2P=CHR+
stabilized ylid mainly E-isomer
Wittig reactions can be done with unhindered ketones
+ Ph3P=CH2
PREPARATION OF CARBOXYLIC ACIDS 1. Oxidation of primary alcohols
ROH
OOH
RH
Hcarboxylic acid
KMnO4
NaOH0 oC
2. Hydrolysis of Esters
R OR'
O
R OH
OOH
R'+
H3O+ or
NaOH, H2O 3. Oxidation of alkylbenzenes
R CO2H -length and nature of R group does not matter-sidechain is cleaved to leave one carbon atom at the oxidation level of an acid
KMnO4
NaOHheat
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4. Carbonation of Grignard reagents
R-Mg-X + CO2 R-CO2-
HClR-CO2H
5. Hydrolysis of nitriles
R-CN + 2 H2OH+ or
baseR-CO2H + NH3
REACTIONS OF CARBOXYLIC ACIDS 1. Acidity. Salt formation R-COOH + R-COO- Na+ +NaOH H2O 2. Conversion into functional derivatives a) Conversion into acid chlorides
R OH
O
R Cl
OSOCl2
PCl5or PCl3
b) Conversion into esters
R OH
O
R OR'
O
+ HOR'H+
+ H2O
c) Conversion into amides
R OH
O
R Cl
O
R NH2
OSOCl2 NH3
3. Reduction
R OH
O
R OHLiAlH4
1o alcohol 4. Reaction with X2
OH
OR OH
OR
X
Br2 or Cl2
red phosphorus
Hell-Volhard-Zelinsky reaction
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PREPARATION OF ACID HALIDES AND ANHYDRIDES From Carboxylic Acids
R OH
O
R Cl
O
R OH
O
R OH
O
R O
O
R
O
R Cl
O
R OH
O
R O
O
R
O
Cl
O
O
ClSOCl2
oroxalyl chloride
Acid Chlorides
Acid Anhydrides
+P2O5
+
oxalyl chloride
REACTIONS OF ACID CHLORIDES AND ANHYDRIDES Acid Chlorides
R OH
O
R Cl
O
R Cl
O
R OH
O
R O
O
R
O
R OR'
O
R NR2
O
R R
O
R H
O
R H
OH
+
water
HOR'
H2NR2
R2Cd
ketone
amide
ester
acid
anhydride
aldehyde
LiAlH(OiPr)3
alcohol
LiAlH4
Acid Anhydrides
R OH
O
R O
O
R
O
R OR'
O
R NR2
O water
HOR'
H2NR2
amide
ester
acid2
+ acid
+ acid
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PREPARATION OF ESTERS 1. From acids
R OH
O
R OR'
O
+ HOR'H+
+ H2O
2. From acid chlorides or anhydrides
R Cl
O
R OR'
O
R O R
OO
R OR'
O
R OH
O
+ HOR' + HCl
+ HOR' +
anhydride 3. From esters: Transesterification
R OR'
O
R OR"
O
HOR'+H+
+HOR" REACTIONS OF ESTERS 1. Conversion into acids and acid derivatives a) Conversion into acids. Hydrolysis
R OH
O
R OR'
O+ HOR'
H+
+ H2O
or HO-
b) Conversion into amides
R NR2
O
R OR'
O+ HOR'H+
+ NR2heat
c) Conversion into esters. Transesterification
R OR'
O
R OR"
O
HOR'+H+
+HOR" 2. Reaction with Grignard reagents
R OR'
O
R R"
R"
OH+ 2 R"MgX
3o alcohol
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3. Reduction to alcohols
R OR'
O
R OHLiAlH4
1o alcohol
+ HOR'
4. Reaction with carbanions. Claisen condensation
OR'
OR OR'
OO
R
R2
3-keto esters
NaOR'
heat
PREPARATION OF AMIDES 1. From acid chlorides
R OH
O
R Cl
O
R NR2
OSOCl2 HNR2
2. From nitriles
RN
R NH2
O
H2O
HCl
heat REACTIONS OF AMIDES 1. Preparation of acids
R NH2
O
R OH
O
H2O
heat
H2SO4
2. Reduction to amines
R NR2
O
R NR2
LiAlH4
an amine
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PREPARATION OF LACTONES
OO O
O OOOHOH
MCPBA
-ring expansion and formation of lactone-oxygen atom introduced to side of ketone thatis most substituted
Baeyer-Villiger Reaction
P2O5
remove water
-5 and 6 membered lactones are easest to form REACTIONS OF LACTONES
O O
O O
OHOH
O OH
LiAlH4
diol
DIBAL-H
lactol
-78 oC, DCM
REACTIONS INVOLVING CARBANIONS 1. Halogenation of ketones
R'
OR R'
OR
X
Br2 or Cl2
H+ or HO-
2. Nucleophilic addition to carbonyl compounds a) Aldol condensation
H
OR H
OOH
RR
H
O
RR
2NaOR'
heat
H+ or
H+
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b) Reactions related to aldol condensation
R'
OR R'
OOH
RR'
RR'
O
R
R'
R
2NaOR'
heat
H+ or
H+
ketone c) Addition of Grignard and organolithium reagents
R H
O
R H
OH
R'
R R"
O
R R"
OH
R'
R OR''
O
R R'
OH
R'
HOR''
+R'MgXorR'Li
aldehyde
R'MgXorR'Li
+
ketone
+R'MgXorR'Li
+esters
d) Wittig reaction
R H
O
R H
R'R"
R R"
O
R R"
R'R"
R3P R'
R"
R3P R'
R"
+
aldehyde
+
ketone
ylidmixture of E and Z
ylidmixture of E and Z
3. Nucleophilic acyl substitution a) Claisen condensation
OR'
OR OR'
OO
R
R2
3-keto esters
NaOR'
heat
27
4. Nucleophilic aliphatic substitution a) Coupling of alkyl halides with organometallic compounds
R X R Li R CuLiR
R' X
R R'
X=Br or I
Li
may be 1o, 2o or 3o
CuI
should be 1o
b) Synthesis of acetylides
H C RNaNH2
Na+RX
R must be primaryX = Br or I
c) Alkylation of malonic ester and acetoacetic ester
OR'
OO
R OR'
OO
RR"
OR'
OO
R'OR"
OR'
OO
R'O
acetoacetic esters
NaOR'
heat+ R"X
NaOR'
heat+ R"X
malonic ester
d) Alkylation of ketones
RO
RO
R'
RO
ROR'
1) LDA, -78 oC, THF
2) R'X
kinetic control
1) KOtBu, HOtBu, heat
2) R'X
thermodynamic control
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5. Addition to conjugated carbonyl compounds. Michael addition
O OCuLi
R
R
O
R
O OCuLi
R
R
O
R
R'
O
O O O
O
R2CuLi
enolate
water
R2CuLi
enolate
R'X
trans-stereochemistry
Micheal addition orconjugate addition
Robinson Annelation
+ NaOMe
MeOH 6. Reformansky Reaction
R R'
OOMe
OR''
BrOMe
OR''
RR'
OH
+Zn
PREPARATION OF AMINES 1. Reduction of nitro compounds Ar-NO2
or
R-NO2
Zn, HCl
H2, Pd/C
Ar-NH2
or
R-NH2 2. Reaction of halides with ammonia or amines
NH3
RXRNH2
RXR2NH
RXR3N
RXR4N+ X-
1o amine 2o amine 3o amine quaternaryammoniumsalt
29
3. Reductive amination
R R'
O
R R'
NHRH2NR
NaCNBH3
pH 5 4. Reduction of Nitriles
RN
R NH2
LiAlH4
or2H2, Pd/C
5. Hofmann degradation of amides
R NH2
O
RNH2
NH2
ONH2
KOBr
+ CO3-
chain loses one carbonatom in length
KOBr
rearrangement withretention of stereochemistry
REACTIONS OF AMINES 1. Basicity. Salt Formation
R2N+H2
2o amine
HClR2NH
ammonium salt
Cl-
2. Alkylation
NH3
RXRNH2
RXR2NH
RXR3N
RXR4N+ X-
1o amine 2o amine 3o amine quaternaryammoniumsalt
3. Conversion into Amides
R' Cl
O
R' NR2
O
R2NH +
amide
30
4. Hofmann Elimination from Quaternary Ammonium Salts
NR2NR3RI+
NaOH, heat
REACTIONS OF BENZENE
BrCl
NO2SO3H
R
X
R
R Cl
O
R
O
Electrophilic Aromatic Substitution of Benzene
Br2, FeBr3
Cl2, FeCl3
HNO3, H2SO4
SO3, H2SO4
AlCl3
rearrangements can occur with primary halides
Friedel-Crafts AcylationFriedel-Crafts Alkylation
AlCl3
Na, NH3(l)
Birch Reduction
BrCl
SO3H
NH2
Reactions to Remove Groups to give Benzene
KOH, heat
Mg, etherthen H2O 1) NaNO2, HCl
2) H3PO2
Mg, etherthen H2O
31
Eelectrophilic Aromatic Substitution on Substituted Aromatic Systems
Ortho/para Directors Meta Directors
-NR2 -NH2 -OH-OR-NHCOMe-OCOMe-R-H
-NR3 -NO2 -CN-SO3H-CHO-COMe-CO2H-CO2Me-CONH2 -NH3
+strong
weak
strong
weak+
Activators-make benzene ring electron richer
Deactivators-make benzene ring electron poor
Halides are deactivating but ortho/para directors!!
-F-Cl-Br-I
REACTIONS OF DIAZONIUM SALTS
NO2 NH2
N2
Cl
Br
I
F
CNOH
NN
NO2
N2
CO2H
Formation of and Reaction of Diazonium Salts
Zn, HCl
NaNO2,HCl
+Cl-
CuCl
KI
HBF4
CuCNH2O,H2SO4
H3PO2 or NaBH4
Diazo dyes
heat
Cu, NaNO2 (aq)
warm+ Cl-
Benzyne
32
CHANGING DIRECTING ABILITY OF GROUPS ON BENZENE RINGS
CO2H
NH2 R
NO2 NH2
CHO
O
Changing Activators into Deactivators
KMnO4
NaNO2, HCl
see diazonium wagonwheel
Changing Deactivators into Activators
H2NNH2, KOH
heat
Zn, HCl
33
DIELS-ALDER REACTION
O
OH
H
O
REWG
REWG
R
EWG
R
EWG
+
diene dienophile
Normal electron demand Diels-Alder reaction requires the dienophile have at least one electron withdrawing group attached and the diene should be electron rich.
Reverse electron demand Diels-Alder reaction requires the diene have at least one electron withdrawing group attached and the dienophile should be electron rich.
Endo vs Exo Products
+ +
exo product-thermodynamic product
endo product-kinetic product
Endo product forms the fastest due to secondary orbital overlap and is the kinetic product.Exo product forms if the reaction proceeds for a longer period of time (i.e. and is reversible).The exo product is thermodynamically more stable due to less steric crowding.
Regiochemistry
+
Diels-Alder reactions with unsymmetrical electron rich dienes and electron poor dienophiles give mainly cyclohexenes with the substituents in either a 1,2- or 1,4- orientation.
+
1,2-product
1,4-product
34
PERICYCLIC REACTIONS
R'
R R
R'
OR'
R
H
O
R
R'H
R'
R
OH
R
R'OH
R
R'OH
OR'
R
OR
O
R
R'OR
OR'
R
NR2
O
R
R'NR2
R'
R
R2N
R
R'R2N
R
R'OH
Cope Reaction
Claisen Reaction
4-enal
Oxy-Cope Reaction
4-enoate
Ortho-ester Claisen Reaction
4-enamide
Ortho-amide Claisen Reaction
Aza-Cope Reaction
H3O+
enamine
These are examples of [3,3] Sigmatropic Rearrangements
35
OTHER SIGMATROPIC REARRANGEMENTS
O OH
O OH
S+ S
S+
S
You have been shown[1,3] and [1,5]-H and alkyl shifts with heat or light. These will not be shown here.
[1,2] Wittig Rearrangement
n-BuLi
[2,3] Wittig Rearrangement
n-BuLi
[1,2] StevensRearrangement
base
Sommelet-Hauser Rearrangements ([2,3] Rearrangement)
base
36
DIPOLAR CYCLOADDITIONS
AB
C 3
D E D EC 8B
A A BC 13
D ED E
C 18BA
N+
NMeO
O
CO2Me
NN
CO2Me
MeO2C
-O O+
O OOO
-+
-+
e.g.
-
ozonide
a)
b)
O
R R'
OR
R'
Electrocyclic Reactions
[2 + 2] Cycloadditions
+light
Follow the Woodward-Hoffman Rules (Chem 453)
heat
not all permutations are shown
+ light
Paterno-Buchi reaction
37
OTHER PHOTOCHEMICAL REACTIONS
O
OHR
O
ORNO
O
OHRON
O
OHRN
OH
O
OHRO H
NOCl
nitrite ester
light
oximealdehyde
-conversion of a delta methyl group to an OH into an aldehyde
Barton Reaction
REARRANGEMENTS
R Cl
O
R CHN2
O OR
R
O
OH
R2R1
R3OH
H
R5
R2
R3
R1
R5
ArAr
O
O
ArOH
O
OHAr
R2
OH
R1OH
R3R4 R2
O
R1
R3R4
O NOH
N OH
Wolff Rearrangement
+ CH2N2
ketene
+N2-chain lengthened by one carbon atom
Arndt-Eistert Synthesis
H2O
Ag2O
H2O
Wagner-Meerwin Migrations
+ H+
-formation of carbocations followed by migration of alkyl, H, or aryl groups
Benzil-Benzilic Acid Rearrangement
NaOH
Pinacol Rearrangement
H+
Beckmann Rearrangement
HONH2
oxime
H+
lactam