Transcript Learning materials

Alkyl halides, Alcohols, Ethers,
Thiols
Required background:
Acidity and basicity
Functional groups
Molecular geometry and polarity
Essential for:
1. Chemistry of carbonyl compounds
2. Reactions under basic conditions
3. Chemistry of acetals and ketals
Outline
1. Structures of alkyl halides, alcohols, and ethers
2. Synthesis of alkyl halides
3. SN1 reaction
4. SN2 reaction
5. E1, E2 reactions
6. Applications of alkyl halides
7. Acidity and basicity of alcohols
8. Dehydration of alcohols
9. Synthesis of ethers
10. Solvents in organic chemistry
C
C
Both carbons are additionally connected only to either carbons, or hydrogens
O
Ethers
sp3
C
A hydroxy-group, attached to a sp3-hybridized carbon
(except for vinyl alcohols)
OH
Alcohols
C
1
C
C
C
o
C
X
2o
C
C
3o
C
X
X
C
A primary compound
A secondary compound
A tertiary compound
This classification does not work for amines!
Example: CH3CH2Br - a primary bromide
Substitution of oxygen with
sulfur in alcohols leads to thiols
Substitution of oxygen with
sulfur in ethers leads to sulfides
Outline
1. Structures of alkyl halides, alcohols, and ethers
2. Synthesis of alkyl halides
3. SN1 reaction
4. SN2 reaction
5. E1, E2 reactions
6. Applications of alkyl halides
7. Acidity and basicity of alcohols
8. Dehydration of alcohols
9. Synthesis of ethers
10. Solvents in organic chemistry
1. Addition of Hal2 or HHal to alkenes (see unit “Alkenes”)
2. Radical halogenation of alkanes
a. Chain initiation
Cl2 = 2Cl. (requires irradiation by light or high temperatures)
b. Chain propagation
RH + Cl. = R. + HCl;
R. + Cl2 = RCl + Cl.
c. Chain termination
2Cl. = Cl2; 2R. = R2;
R. + Cl. = RCl
Br2 reacts like Cl2, but it is less reactive and more selective.
I2 does not react this way, because I. is too stable to split the C-H bond.
F2 is so reactive that it breaks both C-H and C-C bonds:
7F2 + C2H6 = 2CF4 + 6HF
Outline
1. Structures of alkyl halides, alcohols, and ethers
2. Synthesis of alkyl halides
3. SN1 reaction
4. SN2 reaction
5. E1, E2 reactions
6. Applications of alkyl halides
7. Acidity and basicity of alcohols
8. Dehydration of alcohols
9. Synthesis of ethers
10. Solvents in organic chemistry
Terminology of nucleophilic substitution (in general)
R1
R1
R2
X
+
R2
Nu-
R3
R3
Substrate
Leaving group
Substitution
Nucleophile
SN1
Nucleophilic
First overall order
v = k[substrate]
Nu
+
X-
R2
R1
R2
X
R3
R1
+
C
Nu-
R3
NuR1
R1
R2
R3
R2
Nu
Nu
1 : 1 ratio (a racemic mixture)
The SN1 mechanism takes place:
1. For tertiary substrates – always
2. For secondary substrates – sometimes
3. For primary substrates - never
R3
Outline
1. Structures of alkyl halides, alcohols, and ethers
2. Synthesis of alkyl halides
3. SN1 reaction
4. SN2 reaction
5. E1, E2 reactions
6. Applications of alkyl halides
7. Acidity and basicity of alcohols
8. Dehydration of alcohols
9. Synthesis of ethers
10. Solvents in organic chemistry
R2
R1
Nu-
R2
R3
X
-
Nu
R1
+
C
R1
R2
X-
Nu
+
X-
R3
R3
100% inversion of configuration
V = k[substrate][Nu-]
The SN2 mechanism takes place:
1. For tertiary substrates – never
2. For secondary substrates – sometimes
3. For primary substrates - always
Nucleophilicity is the ability to donate a pair of
electrons to a non-hydrogen atom.
Nucleophilicity depends on the ability of the
nucleophile to donate a pair of electrons to H+ (basicity)
and on the influence on such ability from the substrate
(usually polarizability).
Polarizability is characteristic for large atoms and
greatly increases nucleophilicity.
-
HO
H2O
Basicity
Nucleophilicity
-
I
Br
-
Cl
-
-
F
Basicity
Nucleophilicity
Weaker bases make better leaving groups.
Factor
Stability of
carbocation
Steric
hindrance
Nucleophilicity
Good leaving
group
SN1
SN2
+
No effect
No effect
-
No effect
+
+
+
SN1 reactivity
Primary
substrates
Secondary
substrates
SN2 reactivity
Tertiary
substrates
H3C
H3C
OH
NaCl
Cl
H3C
H3C
CH3
CH3
No reaction
Cl
CH3
+
C
H3C
+
-
-
HO
Very bad leaving group
CH3
How to improve the leaving group?
Make it neutral (decrease its basicity)
H3C
H3C
HCl
OH
Cl
H3C
H3C
CH3
CH3
+
SN1
H
Cl
CH3
H3C
-
H
+
O
H3C
C
H
CH3
+
+ H2O
Good leaving group
H3C
CH3
Cl
-
CH 2
NaCl
OH
CH 2
H3C
H3C
Cl
+
-
HO
Very bad leaving group
No reaction
CH 2
HCl
OH
CH 2
H3C
Cl
H3C
+
S N2
H
- H2O
Cl
-
H
CH 2
H3C
+
Good leaving group
O
H
Outline
1. Structures of alkyl halides, alcohols, and ethers
2. Synthesis of alkyl halides
3. SN1 reaction
4. SN2 reaction
5. E1, E2 reactions
6. Applications of alkyl halides
7. Acidity and basicity of alcohols
8. Dehydration of alcohols
9. Synthesis of ethers
10. Solvents in organic chemistry
Regioselectivity of E2
H
H2C
CH3O-
CH 2
H3C
CH 2
CH3
H
H3C
CH3
CH3
Br
Minor product
CH3O-
H
Major product
Reminder:
Alkoxides are stronger bases, than OH- due to weaker solvation
This is another example of the Zaitsev’s rule.
Elimination
2nd order
E2
Elimination E2 requires a strong base
CH 2
Br
CH 2
H2C
CH2
+
Br
-
+
H2O
H
-
HO
OH- is a stronger base in ethanol, than in water,
because it is solvated less
Competing reactions
SN2
E2
Basicity of the attacking group
Nucleophilicity of the attacking group
R1
R1
+
X
R2
H
C
R1
C
R2
C
C
C
R2
H
Common rate limiting step
for E1 and SN1
Y-
Nucleophilicity and basicity of Y- do not affect the reactions E1 and SN1,
because Y- is not involved in the rate limiting step.
Outline
1. Structures of alkyl halides, alcohols, and ethers
2. Synthesis of alkyl halides
3. SN1 reaction
4. SN2 reaction
5. E1, E2 reactions
6. Applications of alkyl halides
7. Acidity and basicity of alcohols
8. Dehydration of alcohols
9. Synthesis of ethers
10. Solvents in organic chemistry
Chloroform (CHCl3) and dichloromethane (CH2Cl2) are
non-flammable organic solvents
Tetrachloroethylene, trichloroethylene are dry-cleaning solvents
Herbicides and pesticides:
Refrigerants (chlorofluorohydrocarbons)
Outline
1. Structures of alkyl halides, alcohols, and ethers
2. Synthesis of alkyl halides
3. SN1 reaction
4. SN2 reaction
5. E1, E2 reactions
6. Applications of alkyl halides
7. Acidity and basicity of alcohols
8. Dehydration of alcohols
9. Synthesis of ethers
10. Solvents in organic chemistry
In a polar solution, acidity of alcohols is lower, than acidity of water
due to the less efficient solvation of the alkoxides (steric reason).
Stronger base
CH3CH2OH + OH-
Stronger acid
CH3CH2O- + H2O
pKa = 15.9
pKa = 15.7
An alkoxide
Primary alcohols
Secondary alcohols
Tertiary alcohols
Acidity
CH3CH2OH,
pKa = 15.9
Primary alcoxides
CH3CH(OH)CH3,
pKa = 17.1
(CH3)3COH,
pKa = 19.2
Secondary alcoxides
Tertiary alcoxides
Basicity
Outline
1. Structures of alkyl halides, alcohols, and ethers
2. Synthesis of alkyl halides
3. SN1 reaction
4. SN2 reaction
5. E1, E2 reactions
6. Applications of alkyl halides
7. Acidity and basicity of alcohols
8. Dehydration of alcohols
9. Synthesis of ethers
10. Solvents in organic chemistry
1. Dehydration
H3C
H3C
CH3
H+
CH3
OH
H3C
H3C
- H+
+
H
E1
H
H3C
CH3
+
O
H3C
H3C
+
C
H
CH3
H
H3C
Zaitsev’s rule: During elimination hydrogen is eliminated from the least
hydrogenated carbon
The Zaitsev’s rule controls regioselectivity of elimination and
based on different stability of transition states with partial double bonds
Outline
1. Structures of alkyl halides, alcohols, and ethers
2. Synthesis of alkyl halides
3. SN1 reaction
4. SN2 reaction
5. E1, E2 reactions
6. Applications of alkyl halides
7. Acidity and basicity of alcohols
8. Dehydration of alcohols
9. Synthesis of ethers
10. Solvents in organic chemistry
1a. Williamson Synthesis (SN2)
R1-O- + R2-I
R1-O-R2 + I-
For primary R2 the reaction works the best
For secondary R2 the reaction works, but elimination takes place as well
For tertiary R2 the reaction almost never works. Only competing elimination takes place.
-
O Na
CH3
+
O
+
Ph
CH 3 I
CH3
Ph
CH3
90% 90%
1b. Alcoholysis (SN1)
H3C
H3C
+
CH3
CH3
H3C
Br
O
H3C
OH
H2C
CH3
H3C
+
CH3
CH3
Minor product (E1)
Major product (SN1)
These reactions are also used to synthesize sulfides.
Ts
OHH3C
SH
H3C
H3C
-
S
O
H3C
S
CH3
H2SO4, 140 oC
..
OH
..
H3C
H3C
O
CH3
+
H
H
..
H
.. +
H3C
O
..
O
CH3
H
+
H3C
S N2
O
CH3
H
For primary and secondary alcohols the reaction requires drastic
conditions. For tertiary alcohols the reaction changes mechanism and
proceeds under much milder conditions.
H3C
..
OH
..
H3C
H3C
C2H5OH,
dilute H2SO4
H3C
O
CH3
H3C
+
H
H3C
H
H3C
+
H3C
H3C
H3C
H
..
O
H3C
+
H3C
O
H
H3C
SN 1
H
..
H3C
..O
C
H3C
+
CH3
CH3
1. Protonation
H
..
..O
R
+
..O
+
H
R
R
R
Oxonium (soluble in water)
F
..
..O
H5C2
b.p.~36 oC
C2H5
+
F
F
F
B
B
F
F
gas
O
H5C2
C2H5
b.p.~110 oC
Outline
1. Structures of alkyl halides, alcohols, and ethers
2. Synthesis of alkyl halides
3. SN1 reaction
4. SN2 reaction
5. E1, E2 reactions
6. Applications of alkyl halides
7. Acidity and basicity of alcohols
8. Dehydration of alcohols
9. Synthesis of ethers
10. Solvents in organic chemistry