189
8.14 Substitution vs. Elimination: Predicting the Products SN2 – nucleophile replaces the LG with inversion (backside
attack) of stererochemistry (stereospecific).
SN1 – nucleophile replaces the LG, unless the intermediate carbocation undergoes rearrangement. The SN1 reaction is not stereospecific.
E2 – The more substituted alkene is usually favored (Zaitsev rule), unless bulky bases (e.g., t-butoxide) are used. The alkene geometry (E vs Z) is determined by the anti- periplanar conformation. In the case of a disubstituted alkene product, the trans geometry is favored.
E1 – The more thermodynamically favored alkene is favored.
This will be the more substituted alkene product (Zaitsev rule), with the most sterically demanding groups trans.
190
Chapter 9. Addition Reactions of Alkenes 9.1 Introduction to Addition Reactions
Substitution Reactions: two reactants exchange parts to give new products (Chapter 7)
H3C H2C OH + H–Br H3C H2C Br + H–OH
Elimination Reaction: a single reactant is split into two (or more) products. Opposite of an addition reaction (Chapter 8)
C CBr H
H HH H
C CH
H H
H+ H-OH + Na-Br
NaOH
Addition Reaction: two reactants add to form a product with no (or few) atoms left over (Chapter 9).
C CH
H H
H+ H-Br C C
Br H
H HH H
95
Hydrohalogenation (Ch. 9.3)
Hydration (Ch. 9.4–9.6)
Hydrogenation (Ch. 9.7)
Halogenation (Ch. 9.8)
Halohydrin formation (Ch. 9.8)
Dihydroxylation (Ch. 9.9, 9.10)
C C
H–XX = Cl, Br, I
XH
H–OHOHH
H–HHH
X–OHOHX
HO–OH OHHO
XXX–X
X = Cl, Br
191
YXC C X–Y+
addition
elimination
9.2: Addition vs. Elimination: A Thermodynamic Perspective
Addition reactions are usually enthalpically favorable, but entropically disfavored.
9.3. Hydrohalogenation
ΔG = ΔH – TΔS
low temperature
high temperature
Reactivity of HX correlates with acidity:
slowest HF << HCl < HBr < HI fastest
XHH–XX = Cl, Br, I
C C
192
96
C CR
H H
H
H–Br C CR
Br
H
HH
H+ C CR
H
H
HH
Br
C CR"
R H
H
H–Br C CR
Br
H
HR"
H+ C CR
H
H
HR"
Br
C CR"
R R'
H
H–Br C CR
Br
R'
HR"
H+ C CR
H
R'
HR"
Br
C CR
H R'
H
H–Br C CR
Br
R'
HH
H+ C CR
H
R'
HH
Br
Regiochemistry
193
Mechanism for hydrohalogenation
194
97
Stereochemistry of hydrohalogenation – hydrohalogenation proceeds through a carbocation intermediate. No stereochemical preference.
H–X X X+
Carbocation rearrangements H–Cl
Cl
+Cl
(40%)expectedproduct
(60%)unexpectedproduct
195
Cationic polymerization
H–A
styrene
polystyrene
9.4 Acid-Catalyzed Hydration – Alkenes - addition of water (H-OH) across the π-bond of an alkene to give an alcohol; opposite of dehydration
C CH2
H3C
H3C
H2SO4, H2O
H3C
OHC
H3C
H3C
196
98
This addition reaction follows Markovnikov’s rule The more highly substituted alcohol is the product and is derived from the most stable carbocation intermediate. Reactions works best for the preparation of 3° alcohols, but poorly for 1°alcohols.
Mechanism of the acid-catalyzed hydration
197
9.5 Oxymercuration-Demercuration – The acid-catalyzed hydration is not a general method for the hydration of an alkene.
Oxymercuration – Demercuration: a general (2-step) method for the Markovnokov hydration of alkenes.
H3C OC
OAc= acetate =
NaBH4 reduces the C-Hg bond to a C-H bond
C4H9 CC 1) Hg(OAc)2, H2O
C4H9 CC
H
Hg(OAc)
H
OHHH
H
H 2) NaBH4
C4H9 CC
H
H
H
OHH
198
99
9.6 Hydroboration-Oxidation - Anti-Markovnikov addition of H-OH; syn addition of H-OH
CH31) B2H6, THF2) H2O2, NaOH, H2O CH3
H
HHO
Diborane 2 BH3
HB
HB
H
HH
H
O OBH
HH
Mechanism of hydroboration
199
200
Hydration of alkenes summary: addition of water (H–OH) across the π-bond of an alkene to give an alcohol.
1. Acid catalyzed hydration- Markovnikov addition of H–OH Not a good method for hydration of an alkene
2. Oxymercuration- Markovnikov addition H–OH
3. Hydroboration- Anti-Markovnikov addition of H–OH,
Syn addition of H–OH
CH3 1) Hg(OAc)2, H2O2) NaBH4
CH3HO
HH
CH31) B2H6, THF2) H2O2, NaOH, H2O CH3
H
HHO
100
9.7 Catalytic Hydrogenation – Addition of H2 across the π-bond of an alkene to give an alkane. This is a reduction.
201
R RH2, Pd
The catalysts (Pd, Pt, Rh, Ni) is not soluble in the reaction media; thus, this process is referred to as a heterogenous catalysis.
The reaction takes places on the surface of the catalyst. Thus, the rate of the reaction is proportional to the surface area of the catalyst.
Stereospecificity – The addition of H2 across the π-bond is syn, i.e., from the same face of the double bond.
CH3
CH3
H2, Pd CH3
CH3
H
Hsyn addition of H2
(+ enantiomer)
CH3
H
H
CH3anti addition of H2
(not observed)
202
H2C CH2
H2C CH2H2
H HH2C CH2H H
H CCH
HH
HH
C CH
H
H
HH
H
Mechanism: The catalyst assists in breaking the π-bond of the alkene and the H-H σ-bond.
Carbon-carbon π-bond of alkenes and alkynes can be reduced to the corresponding saturated C-C bond. Other π-bond bond such as C=O (carbonyls) and C≡N (nitriles) are not easily reduced by catalytic hydrogenation. The C=C bonds of aromatic rings are not easily reduced.
101
203
9.8 Halogenation and Hydrohydrin Formation Addition of X2 (Cl2 and Br2) to Alkenes
C C C C
XX
1,2-dihalidealkene
X2(vicinal dihalide)
+ Br2
Br
Br
+Br
Br
not observed
Stereochemistry – anti addition of X2 across the π-bond
CH3 CH3Br
BrH
Br2
204
Mechanism for halogenation
Bromonium ion intermediate explains the stereochemistry of Br2 addition.
102
205
Halohydrin formation
C C C COHX
halohydrinalkene
"X-OH"
X
OH
antistereochemistry
X2, H2O+ HX
206
Regiochemistry of halohydrin formation – For unsymetrical alkenes, halohydrin formation is Markovnikov-like in that the orientation of the addition of X–OH can be predicted by considering carbocation stability
CH3 CH3HO
BrH
Br2, H2O+ HBr
103
207
Organic molecules are sparingly soluble in water as solvent. The reaction is often done in a mix of organic solvent and water using N-bromosuccinimide (NBS) as he electrophilic bromine source.
DMSO, H2ON
O
O
Br+Br
OH
N
O
O
H+
Note that the aryl ring does not react!!! 9.9 Anti Dihydroxylation formal addition of HO-OH across the π-bond of an alkene to give a vicinal-diol. This is an overall oxidation. Vicinal diols have hydroxyl groups on adjacent carbons (vic-diols, 1,2-diols, glycols)
C CH
H H
HHO
OH"HO–OH"
RCO3H OH3O+
hydrolysis
OH
OH
racemic
Epoxide (oxirane): three-membered ring, cyclic ethers.
208
R OH
O
R O
O
OH
carboxylic acid peroxyacid
HO–OH
peroxide
Peroxyacids Epoxidation mechanism
Stereochemistry of the epoxidation of alkenes: syn addition of oxygen. The geometry of the alkene is preserved in the product
Groups that are trans on the alkene will end up trans on the epoxide product. Groups that are cis on the alkene will end up cis on the epoxide product.
104
209
Epoxide hydrolysis to anti vicinal diols 9.10 Syn Dihydroxylation
OsO4
OOs
O
O
O
osmate esterintermediate
NaHSO3, H2OOH
OH
210
9.11 Oxidative Cleavage (ozonolysis) - oxidative cleavage of an alkene to carbonyl compounds (aldehydes and ketones). The π- and σ-bonds of the alkene are broken and replaced with C=O double bonds. 3 O2 2 O3
electrical discharge Ozone (O3): O O
O _+
1) O3
2) (H3C)2S or
Zn, H2O
1) O3
2) (H3C)2S or
Zn, H2O
1) O3
2) (H3C)2S or
Zn, H2O
O
O
O
O
H
+
O
H
O
R2
R1 R3
R4
O3, CH2Cl2-78 °C O
OO
R1R2 R4
R3 O
OOR1
R2 R4
R3
molozonide ozonide
R1
R2
OR4
R3O+
+ ZnO or (H3C)SO
Zn-or-
(H3C)2S
mechanism
105
211
9.12 Predicting the Products of an Addition Reaction
1. What atoms or groups are being added to the double bond. Account for these groups in the reagents.
2. What is the regiochemistry: Markovnikov vs anti-Markovnikov
3. What is the stereochemistry: Syn vs Anti addition, or no stereochemical preference.
X
H–X
OH
H3O+
-or-1) Hg(OAc)2, H2O2) NaBH4
1) B2H6, THF, 2) HOOH, NaOH H2O
syn addition
H2, PdH3COH
syn addition
X
X
X2
OH
X
X2, H2O
anti addition anti addition
OH
OH
OH
OH
1) RCO3H2) H2O
1) OsO42) NaHSO3
anti addition syn addition
Markovnikov MarkovnikovOH
anti-Markovnikov Markovnikov-likeH H
H
H
H
212
9.13 Synthesis Strategies – Construct larger, more complex molecules out of smaller ones using known and reliable reactions
One-step synthesis:
Substitution
Elimination
Addition Change the position of the leaving group (halide or alcohol)
Change the position of a π-bond Retrosynthetic analysis – working a synthesis problem backward from the desired product to the starting substrate.
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