wwu -- chemistry nucleophilic substitution reactions: reactions and synthetic applications
Post on 18-Dec-2015
230 Views
Preview:
TRANSCRIPT
WWU -- ChemistryWWU -- Chemistry
Nucleophilic Substitution Nucleophilic Substitution Reactions:Reactions:
Reactions and Synthetic Reactions and Synthetic ApplicationsApplications
WWU -- ChemistryWWU -- Chemistry
Assignment for Chapter 12Assignment for Chapter 12 Read Sections 12.0 through 12.4Read Sections 12.0 through 12.4 SKIP Pages 1108 (bottom) through 1112 (Sect. 12.4)SKIP Pages 1108 (bottom) through 1112 (Sect. 12.4) New material on N-bromosuccinimide reactionsNew material on N-bromosuccinimide reactions SKIP Sections 12.5 through 12.6SKIP Sections 12.5 through 12.6 Read Sections 12.7 through 12.8Read Sections 12.7 through 12.8 SKIP Section 12.9SKIP Section 12.9 Read Sections 12.10 through 12.11Read Sections 12.10 through 12.11 SKIP Section 12.12SKIP Section 12.12 Read Sections 12.13 through end of chapterRead Sections 12.13 through end of chapter
ORGANIC NOMENCLATURE: Alcohols and EthersORGANIC NOMENCLATURE: Alcohols and Ethers
WWU -- ChemistryWWU -- Chemistry
Problem AssignmentProblem Assignment
In-Text ProblemsIn-Text Problems– 12-1 through 12-812-1 through 12-8
– 12-12 through 12-2412-12 through 12-24
– 12-27 through 12-3212-27 through 12-32
– 12-34 through 12-3912-34 through 12-39
End-of-Chapter ProblemsEnd-of-Chapter Problems– 40 through 4240 through 42
– 46 through 5446 through 54
– 57 through 6157 through 61
– 63 through 7563 through 75
WWU -- ChemistryWWU -- Chemistry
General Rules for NomenclatureGeneral Rules for Nomenclature
Choose the longest continuous chain of Choose the longest continuous chain of carbon atoms which carbon atoms which includes the carbon atom includes the carbon atom bearing the functional groupbearing the functional group. This chain will . This chain will identify the parent hydrocarbon.identify the parent hydrocarbon.
Number the parent carbon chain from the end Number the parent carbon chain from the end nearest the functional groupnearest the functional group, irrespective of , irrespective of other substitution. other substitution.
Indicate the substituents by name Indicate the substituents by name andand number. number. Assign a number to the carbon atom bearing Assign a number to the carbon atom bearing the functional group.the functional group.
Combine all parts into one word, using correct Combine all parts into one word, using correct punctuation.punctuation.
WWU -- ChemistryWWU -- Chemistry
General Rules for General Rules for Nomenclature (continued)Nomenclature (continued)
Show the presence of the functional group by Show the presence of the functional group by replacing the replacing the -e-e of the alkane ending of the alkane ending (sometimes the (sometimes the -ane-ane) with the appropriate ) with the appropriate ending for the functional group. Show the ending for the functional group. Show the position of the functional group by inserting a position of the functional group by inserting a number into the name immediately number into the name immediately beforebefore the the name of the parent chain.name of the parent chain.
WWU -- ChemistryWWU -- Chemistry
LOCANT PREFIX N STEM SUFFIX
numbers substituents number -ALK(AN)- ending
Block Diagram for Block Diagram for NomenclatureNomenclature
WWU -- ChemistryWWU -- Chemistry
Nucleophilic SubstitutionNucleophilic Substitution
Nu: + X:+ R X Nu R
WWU -- ChemistryWWU -- Chemistry
Nucleophilic SubstitutionNucleophilic Substitution
+ :Nu + :X:..
..
_R X R Nu
substrate nucleophile product leaving group
chloridebromideiodidehydroxidewateralkoxidesalcoholscyanideaminessulfidesacetylidescarbanionscarboxylates
chloridebromideiodidewateralcoholssulfonatesamines
WWU -- ChemistryWWU -- Chemistry
Assisted Nucleophilic Assisted Nucleophilic SubstitutionSubstitution
+ H Br+ _
+R OH R Br H O H
WWU -- ChemistryWWU -- Chemistry
Assisted SAssisted SNN2: Mechanism2: Mechanism1)
2)
R CH2 O + HH R CH2 O H
H
R CH2 O H
H
Br +slow
Br CH2 R + O
H
H
WWU -- ChemistryWWU -- Chemistry
Assisted SAssisted SNN1: Mechanism1: Mechanism
CH3 C C
CH3
O
C CH3
H
CH3 C C
CH3
O
C CH3
H
H
1)
2)
3)
+ H
CH3 C C
CH3
O
C CH3
H
H
CH3 C C
CH3
OC CH3
H
H+
CH3 C C
CH3
C CH3 + Cl CH3 C C
CH3
C CH3
Cl
slow
WWU -- ChemistryWWU -- Chemistry
Alcohol + Hydrogen HalideAlcohol + Hydrogen Halide
This method is best with tertiary alcoholsThis method is best with tertiary alcohols
This reaction works very slowly with primary This reaction works very slowly with primary and secondary alcohols.and secondary alcohols.
Rearrangements are possible!Rearrangements are possible!
WWU -- ChemistryWWU -- Chemistry
Neopentyl Alcohol Neopentyl Alcohol + Lucas Reagent+ Lucas Reagent
CH3 C CH2
CH3
CH3
O H ZnCl2 CH3 C CH2
CH3
CH3
O H
ZnCl2
CH3 C CH2
CH3
CH3
O H
ZnCl2
1)
2)
3)
4)
5)
+
slowCH3 C CH2
CH3
CH3
O H
ZnCl2
+
CH3 C CH2
CH3
CH3
CH3 C CH2
CH3
CH3
CH3 C CH2
CH3
CH3 + Cl CH3 C CH2
CH3
CH3
H + HO ZnCl2 H2O + ZnCl2
Cl
WWU -- ChemistryWWU -- Chemistry
Alcohols + Phosphorus HalidesAlcohols + Phosphorus Halides
3 + PX3
3 +
heatR OH
R X P OH
OH
OH
WWU -- ChemistryWWU -- Chemistry
Alcohol + Phosphorus HalideAlcohol + Phosphorus Halide
This method is best for primary and This method is best for primary and secondary alcohols.secondary alcohols.
This method is generally unsuccessful with This method is generally unsuccessful with tertiary alcoholstertiary alcohols
Rearrangements do not happen with this Rearrangements do not happen with this method.method.
WWU -- ChemistryWWU -- Chemistry
Preparation of TosylatesPreparation of Tosylates
..:R O
H
CH3SCl
O
O
+
CH3S
O
O
OR..
..
N
+ H Cl
???
p-Toluenesulfonyl chloride "Tosyl chloride"
a p-Toluenesulfonate a "Tosylate"
TsCl
R-OTs
WWU -- ChemistryWWU -- Chemistry
Which Alkyl Halide Should I Which Alkyl Halide Should I Use?Use?
If the halide is a better leaving group, the If the halide is a better leaving group, the reaction will go in higher yield.reaction will go in higher yield.
II-- > Br > Br-- > Cl > Cl--
If the halide is cheaper, the reaction will be If the halide is cheaper, the reaction will be more economical.more economical.
ClCl-- > Br > Br-- > I > I--
WWU -- ChemistryWWU -- Chemistry
Which Alkyl Halide Should I Which Alkyl Halide Should I Use? (Part Two)Use? (Part Two)
Best compromise…Best compromise…
Alkyl bromides!Alkyl bromides!
Exception: For CHException: For CH33—X, use—X, use
Methyl iodideMethyl iodide
WWU -- ChemistryWWU -- Chemistry
Addition of Hydrogen Halides Addition of Hydrogen Halides to Double Bondsto Double Bonds
CH CH2RHX
R CH CH3
X
+ R CH2 CH2
X
major minor
This reaction follows Markovnikov’s Rule
Chapter 8, Section 8.4
WWU -- ChemistryWWU -- Chemistry
Free Radical Halogenation of Free Radical Halogenation of AlkanesAlkanes
R CH2 CH3
X2
lightR CH CH3 R CH2 CH2
+
X X major minor
Chapter 3, Section 3.17
WWU -- ChemistryWWU -- Chemistry
Allylic Halogenation with Allylic Halogenation with NN-Bromosuccinimide-Bromosuccinimide
CH CH2CH2R + N
O
O
BrCCl4
heat, light, orperoxides
CH CH2CHR + N
O
O
H
Br
N-Bromosuccinimide (NBS)
WWU -- ChemistryWWU -- Chemistry
Mechanism – Step 1Mechanism – Step 1
N
O
Br
O
free radical
initiatorN
O
O
+ Br
WWU -- ChemistryWWU -- Chemistry
Mechanism – Step 2Mechanism – Step 2
R CH CH CH2
HBr
R CH CH CH2
BrH++
allylic radical
R CH CH CH2 R CH CH CH2
slow
WWU -- ChemistryWWU -- Chemistry
Mechanism – Mechanism – Step 3Step 3
N
O
Br
O
H Br
N
O
Br
O
BrH
N
O
O
H + Br Br
Succinimide
N
O
O
H
WWU -- ChemistryWWU -- Chemistry
Mechanism – Step 4Mechanism – Step 4
R CH CH CH2
+Br Br
R CH CH CH2
+Br
Br
WWU -- ChemistryWWU -- Chemistry
Halogenation at a Benzylic Halogenation at a Benzylic PositionPosition
+ N
O
O
XCCl4
heat, light, orperoxides
+ N
O
O
H
CH2 R
CH R
XX = Br or Cl
WWU -- ChemistryWWU -- Chemistry
Benzylic Substitution – Benzylic Substitution – Mechanism Step 2Mechanism Step 2
Br
BrH+
+
CH R
H
slowCH R
a benzyl radical
WWU -- ChemistryWWU -- Chemistry
Conversion of Alkyl Halides to Conversion of Alkyl Halides to AlcoholsAlcohols
+ H2O +
+ +
R OH
XR OH
H X R X
R X OH
SN1
SN2
WWU -- ChemistryWWU -- Chemistry
Synthesis of EthersSynthesis of Ethers
+ +R X R O R H X R OH
WWU -- ChemistryWWU -- Chemistry
Williamson Ether SynthesisWilliamson Ether Synthesis
+ + 1/2 H2
..
..:
_
+ +..
..
R OH Na(0)
R O Na+
R O R X R O R X
SN2
WWU -- ChemistryWWU -- Chemistry
General Reaction of EpoxidesGeneral Reaction of Epoxides
: :
Nu:
..:..
..
..
Nu C C O
R
R
R
R
Nu C C OH
R
R
R
R
CR
R
C R
R
O
H+
WWU -- ChemistryWWU -- Chemistry
Under Acidic Conditions…Under Acidic Conditions…
:
Nu:
..
..
+
CR
R
C R
R
O
H
Nu C C OH
R
R
R
R
WWU -- ChemistryWWU -- Chemistry
Reactions of EpoxidesReactions of Epoxides
: :_
+(H )
+
HBr +
:OH..
_
..+
(H )+
H +: :
+
CH2CH2
O
CH2CH2
O
CH2CH2
O
CH2CH2
O
C N N C CH2 CH2 OH
Br CH2 CH2 O H
OH CH2 CH2 OH
H
O
H OH CH2 CH2 O H
WWU -- ChemistryWWU -- Chemistry
More Reactions of EpoxidesMore Reactions of Epoxides
NH3
+
+
R:_
+(H )
+
CH2CH2
O
CH2CH2
O
CH2CH2
O
NH2 CH2 CH2 OH
R NH2R NH CH2 CH2 OH
R CH2 CH2 OH
WWU -- ChemistryWWU -- Chemistry
Reactions of Epoxides in Basic Reactions of Epoxides in Basic MediumMedium
CH CH2
O
R + Nu R CH CH2 Nu
OH
WWU -- ChemistryWWU -- Chemistry
Reactions of Epoxides in Acidic Reactions of Epoxides in Acidic Medium Medium
CH CH2
O
R + Nu R CH CH2 OH
H
Nu
WWU -- ChemistryWWU -- Chemistry
Synthesis of Heliannuol ESynthesis of Heliannuol E
CH3
OCH3
O
CHCH2
CHC
CHCH2
CH3
CH3
O
H CH3
OCH3
O
CHCH2
CHCH2
CHC
OH
CH3
CH3
KOH
DMSO
Hydrolyze to remove methyl group.
WWU -- ChemistryWWU -- Chemistry
Synthesis of Heliannuol CSynthesis of Heliannuol C
CH3
OCH3
O
CHCH2
CHC
CHCH2
CH3
CH3
O
H CH3
OCH3 CH
CHCH2
SnCl4
OC
CH
CH2
CH3
CH3
OH
Hydrolyze to remove methyl group.
WWU -- ChemistryWWU -- Chemistry
Synthesis Problem #1Synthesis Problem #1
OH Br
WWU -- ChemistryWWU -- Chemistry
Outline the MechanismOutline the Mechanism
HBrCH3 C CH CH3
CH3
CH3 OH
CH3 C CH CH3
CH3
Br
CH3
WWU -- ChemistryWWU -- Chemistry
HBr or PBrHBr or PBr33??????
CH CH CH2 Br
CH3 C CH CH3
CH3
CH3 OH
CH3 C CH CH3
CH3
CH3 Br
CH CH CH2 OH
WWU -- ChemistryWWU -- Chemistry
Synthesis Problem #2Synthesis Problem #2
CH O
CH3
CH2 CH3CH3 CH2 Br
WWU -- ChemistryWWU -- Chemistry
Synthesis of MTBESynthesis of MTBE(Methyl (Methyl terttert-Butyl Ether)-Butyl Ether)
CH3 C O CH3
CH3
CH3
WWU -- ChemistryWWU -- Chemistry
Synthesis Problem #3Synthesis Problem #3
CH3 CH CH2 CH3 CH CH2 OH
OH
WWU -- ChemistryWWU -- Chemistry
Reactions of EpoxidesReactions of Epoxides
: :_
+(H )
+
HBr +
:OH..
_
..+
(H )+
H +: :
+
CH2CH2
O
CH2CH2
O
CH2CH2
O
CH2CH2
O
C N N C CH2 CH2 OH
Br CH2 CH2 O H
OH CH2 CH2 OH
H
O
H OH CH2 CH2 O H
WWU -- ChemistryWWU -- Chemistry
More Reactions of EpoxidesMore Reactions of Epoxides
NH3
+
+
R:_
+(H )
+
CH2CH2
O
CH2CH2
O
CH2CH2
O
NH2 CH2 CH2 OH
R NH2R NH CH2 CH2 OH
R CH2 CH2 OH
WWU -- ChemistryWWU -- Chemistry
What are the Products?What are the Products?
+
+_
CH3 C NH2
CH3
CH3
CH3 Cl
CH3 CH2 CH2 Br C N
WWU -- ChemistryWWU -- Chemistry
Synthesis Problem #4Synthesis Problem #4
Starting with alcohols, synthesize:
CH3 CH2 CH2 CH2 C C CH2 CH2 CH3
WWU -- ChemistryWWU -- Chemistry
The Synthesis Problem from The Synthesis Problem from Hell!Hell!
CH3 CH2 CH CH CH3
CH3
OH
CH3 CH2 CH CH CH2
CH3
WWU -- ChemistryWWU -- Chemistry
Try this!Try this!
O CH2
CH2OH
???
Plus any additional needed reagents and solvents
WWU -- ChemistryWWU -- Chemistry
..
..
+
Methionine
ATP
+
+_
S-Adenosylmethionine
(S-Adm)
O
H
OH
H
OH
HH
N N
NN
NH2
CH2OPOPOPOH
O
OH
O
OH
O
OH
OH C CH CH2 CH2 S CH3
O NH2
O
H
OH
H
OH
HH
N N
NN
NH2
CH2SCH3
CH2
CH2
CH
COOH
NH2
O P P
O O
OH OH
P OH
O
OH
WWU -- ChemistryWWU -- Chemistry
+
_
Tyrosine
O2
+
_
DOPA
+
- CO2
+
Dopamine
O2
+
Norepinephrine
(Noradrenaline)
(S-Adm)
Epinephrine
(Adrenaline)
OH CH2 C COO
NH3
H
CH3 R
OH CH C H
NH3
H
OH
OH
OH CH2 C H
NH3
H
OH
OH CH C H
NH2
H
OH
OH
CH3
OH CH2 C COO
NH3
H
OH
WWU -- ChemistryWWU -- Chemistry
Change in Assignment Change in Assignment (August 11, 2004)(August 11, 2004)
Include the following sections:Include the following sections:– 12.912.9– 12.1012.10– 12.1112.11– 12.1412.14– 12.1512.15
top related