CHAPTER 10 ALKYL HALIDES Alkyl halides are used ...
CHAPTER 10 ALKYL HALIDES Alkyl halides are used as refrigerants, solvents, pesticides and fumigating agents. Are naturally occurring in marine organisms.
Classification of halides: R
X
X Aryl halides
Alkyl halides 1˚, 2˚, 3˚
C
CX Benzylic halides
C
C
C CX
X Vinyl halides
Allylic halides
Nomenclature: We are building on what we already have learned. Halides are always names as substituents. So name as alkane, alkene or alkyne (later we will consider other functional groups as parent name). 1. Longest chain (if double bond (=) or triple bond, include in name). 2. Number nearest the first substituent a. Use all numbers and di, tri, etc. prefixes. 3. If can nuber from either end as in rule # 2, then lower number is given to the first substituent alphabetically. Common names you should learn to recognize: iodomethane dichloromethane trichloromethane tetrachloromethane
methyl iodide methylene chloride chloroform (iodoform, bromoform) carbon tetrachloride or carbon tet.
1
Comparison of CH3-X bonds Halide
Bond length (Å)
BDE kJ/mol (kcal/mol) 452 (108)
Dipole (µ) D
fluoro
1.39
1.85
chloro
1.78
351
(84)
1.87
bromo
1.93
293
(70)
1.81
iodo
2.14
234
(56)
1.66
Preparation of Halides: Some we have already seen as reviewed below: 1. From Alkenes X X2
X
CH3
HX X
CH3 NBS /D MS OH
CH3
2O
HO
+
Br CH3
Br CH3
OH
(Unequal mixture of diastereomers)
2
+ enantiomer (racemic mix)
2. Free radical halogenation of alkanes; Review steps of mechanism from Chapter 5. Overall reaction
CH4 +
Difficult reaction to control. Mixture of products is almost always obtained. But can control somewhat to examine reactivity of different hydrogen to this substitution.
Cl2
CH3Cl + HCl Cl2 CH2Cl 2 Cl2
CHCl3 Cl2
CCl4
Reactivity toward chlorination is in order R3 C. > R2 CH > RCH2 , that is 3˚ > 2˚ > 1˚, which is the order of stability of carbon radicals. Can examine this be looking at the ratio of monochlorination products in a compound that contains both 2˚ and 1˚ hydrogens that can be replaced. CH3CH2CH2 CH3
+
Cl2
CH3CH2CH2 CH2 Cl
light
+ CH3 CH2CHClCH3
Obtained in ratio of 30 :
70
There are six 1˚ hydrogens and four 2˚ hydrogens, but do not get a statistical ratio of products. 30 Since get 30% of 1˚ substitution and there are six of these H’s, each is 6 = 5% responsible for the product. 70 For the 2˚ Hs, each is responsible for 4 = 17.5% of product. 17.5 The ratio of 5 is equal to 3.5:1. So the 2˚ hydrogens have a relative rate of substitution that is 3.5 times faster than 1˚ hydrogens.
3
Can do the same calculation with 1˚ vs. 3˚ and find out that 3˚ hydrogens are replaced in radical chlorination 5 times faster than 1˚ hydrogens. CH3 H3C CH CH3
+ Cl2
hn
CH3 CH3 + H3C C CH3 H3C CH CH2Cl Cl Obtained in ratio of 35 : 65
Bomination is more "selective". When examine a reaction for bromination, find that 3˚ hydrogens are replaced 1000 times faster than 1˚.
CH3 H3C CH CH3
+ Br2
hn
CH3 H3C C CH3 + Br Obtained in > 99%
CH3 H3C CH CH2Br
Less reactive, more selective (Br2) More reactive, less selective (Cl2) In free radical chlorination get a mixture of products. In bromination, if a 3˚ H present get substitution there over others. 3. Allylic Bromination of Alkenes Using slow generation of Br2 from NBS is presence of light - get substitution rather than addition to the alkene double bond. Br
O
NBS
NBS =
hn, CCl 4
N Br
N-Bromosuccinimide
O
This is radical halogenation but only hydrogens on sp3 carbon adjacent to alkene sp2 carbons are substituted. These are allylic hydrogens.
4
Allylic hydrogens H
H
H Alkyl hydrogens H
H
Vinylic hydrogens
H
Free radical stability Allylic > 3˚ > 2˚ > 1˚ > methyl > vinylic H Br
H
H
Br Br
+
Br
H + Br
Allylic radical is stabilized by resonance. H C
H C H
H C
H
H
C
C H
H
H H
d C
C d C
In a symmetrical alkene such as cyclohexene, either allylic carbons may be substituted and get the same product. Br NBS
KOH
hn, CCl 4
This is a "conjugated diene".
In an unsymmetrical alkene get a mixture of products. Cannot always predict which you will get more of. But can explain experimental data after you examine the
5
reaction and see which product is produced in greater yield. Sometimes two opposing phenomena are at work. NBS
CH3CH2CH2 CH2 CH=CH2
CH3CH2CH2 CH=CH-CH2 Br + CH3 CH2 CH2CHBrCH=CH2
hn
4. Alkyl Halides from Alcohols The most general method of preparing halides is from alcohols. a) With conc H-X R OH
+
H X
R X + HOH X = Cl, Br, I
Best with 3˚ alcohols to 3˚ halides. Primary and secondary are slower with this reagent.
OH
+ HBr
Br
3˚ alcohol
3˚ halide
b) For 2˚ and 1˚ alcohols, use PBr3 (phosphorous tribromide) and SOCl2 (thionyl chloride). OH CH3CH2 CHCH2CH3 OH CH3CH2 CHCCH2CH3 O
Br CH3CH2 CHCH2CH3
PBr3 SOCl2
CH3CH2
Cl CH CCH2CH3 O
With these latter two reagents, one is less likely to get rearranged products. Mechanism will be examined in a later chapter.
Reactions of Alkyl Halides 1. Grignard Reagents 6
Grignard reagents are organometallic compounds that have many uses. We will look at only one here. Others will be examined in later chapters.
R X
anhydrous
+ Mg
R Mg X
ether or THF
X = Cl, Br, I
Bromine and iodine are best (chlorine is slower - less reactive) Fluroides usually do not react. CH3CH2Cl
+
Mg
Br + Mg
Br
+ Mg
anh. ether
CH 3CH2MgCl MgBr
anh. ether
anh. ether
MgBr
Highly polar bond to metal but dipole is reversed from most of what we have seen so far. d-
C
d+ MgX
The carbon is d - and the metal is d +. Carbon in a Grignard reagent reacts as if it were a carbanion –A POWERFUL BASE!. Grignards react with proton donors. Are strong proton acceptors in addition to being nucleophiles. Below are some proton donors that react with Grignard reagents. O H OH
RO
H
R C OH
The reaction with water is shown. An alkane is the product.
7
R NH
d- R d+ Mg
+
X
d+ H d- OH
R
H + MgX(OH)
In preparing a Grignard for some subsequent use, must be very careful in reaction conditions and in the presence of other functional groups in the molecule (other than the halide). Br CH3 CHCH2 CH2CH2OH
Mg
CH3
MgBr CHCH2 CH2CH2OH
NO!
a. Solvent must be anhydrous (NO WATER) b. Functional groups with an active hydrogen cannot be present. (We will see in later chapters that some other groups also cannot be present). 2. Organometallic Coupling Reactions These reactions allow us to make new carbon-carbon bonds, increasing the size of the molecule. CH3CH2CH2 -Br
2Li
CH3CH2CH2 Li +
LiBr
These reagents are both nucleophiles and bases. The preparation of organo lithium compounds from halides works best with primary (1˚) halides.
CH3CH2-Br 2CH3CH2Li
+
CuI
CH3 CH2 Li +
LiBr
(CH3 CH2)2 Cu Li
+
LiI
This part works best with primary halides
Gilman Reagent
From these organolithium compounds we can make a new organometallic called a Gilman reagent. Gilman reagents are used to make new carbon-carbon bonds in coupling reactions. 8
(CH3CH2)2 Cu Li
+
R-I
R-CH2CH3
+ LiI
CH3CH2Cu
This part of synthesis can be done with any kind of halide vinyl,,,,,,,,,,,alkyl,,,,,,,,,,,,,,aryl ,,,,,,,,,,,,,,,,
In this coupling reaction, can use vinyl, aryl or alkyl halides.
Oxidations and reductions in organic chemistry. Oxidation = Gains in bonds of electronegative elements: O, halogen, N, S, etc, and/or loss of bonds to hydrogen. Reduction = Gain in bonds to H and/or loss of bonds to electronegative elements. Carbon (diamond/graphite/buckyballs)
[H] CH4 [O] [H]
H
C
[O]
O
[O]
O OH [H]
H
[H]
C
[O]
[O] H
CH3OH [H]
Where [O] is symbol for oxidation and [H] is symbol for reduction
O C CO2 + H2O HO OH Carbonic acid: In equilibrium with carbon dioxide and water
Br2
Br C-C
Br
H C-C
Br
[O]
C=C
HBr
H2
H C-C Hr
[H]
9
Neither [O] nor [H]
Classification of halides: R
X
X Aryl halides
Alkyl halides 1˚, 2˚, 3˚
C
CX Benzylic halides
C
C
C CX
X Vinyl halides
Allylic halides
Nomenclature: We are building on what we already have learned. Halides are always names as substituents. So name as alkane, alkene or alkyne (later we will consider other functional groups as parent name). 1. Longest chain (if double bond (=) or triple bond, include in name). 2. Number nearest the first substituent a. Use all numbers and di, tri, etc. prefixes. 3. If can nuber from either end as in rule # 2, then lower number is given to the first substituent alphabetically. Common names you should learn to recognize: iodomethane dichloromethane trichloromethane tetrachloromethane
methyl iodide methylene chloride chloroform (iodoform, bromoform) carbon tetrachloride or carbon tet.
1
Comparison of CH3-X bonds Halide
Bond length (Å)
BDE kJ/mol (kcal/mol) 452 (108)
Dipole (µ) D
fluoro
1.39
1.85
chloro
1.78
351
(84)
1.87
bromo
1.93
293
(70)
1.81
iodo
2.14
234
(56)
1.66
Preparation of Halides: Some we have already seen as reviewed below: 1. From Alkenes X X2
X
CH3
HX X
CH3 NBS /D MS OH
CH3
2O
HO
+
Br CH3
Br CH3
OH
(Unequal mixture of diastereomers)
2
+ enantiomer (racemic mix)
2. Free radical halogenation of alkanes; Review steps of mechanism from Chapter 5. Overall reaction
CH4 +
Difficult reaction to control. Mixture of products is almost always obtained. But can control somewhat to examine reactivity of different hydrogen to this substitution.
Cl2
CH3Cl + HCl Cl2 CH2Cl 2 Cl2
CHCl3 Cl2
CCl4
Reactivity toward chlorination is in order R3 C. > R2 CH > RCH2 , that is 3˚ > 2˚ > 1˚, which is the order of stability of carbon radicals. Can examine this be looking at the ratio of monochlorination products in a compound that contains both 2˚ and 1˚ hydrogens that can be replaced. CH3CH2CH2 CH3
+
Cl2
CH3CH2CH2 CH2 Cl
light
+ CH3 CH2CHClCH3
Obtained in ratio of 30 :
70
There are six 1˚ hydrogens and four 2˚ hydrogens, but do not get a statistical ratio of products. 30 Since get 30% of 1˚ substitution and there are six of these H’s, each is 6 = 5% responsible for the product. 70 For the 2˚ Hs, each is responsible for 4 = 17.5% of product. 17.5 The ratio of 5 is equal to 3.5:1. So the 2˚ hydrogens have a relative rate of substitution that is 3.5 times faster than 1˚ hydrogens.
3
Can do the same calculation with 1˚ vs. 3˚ and find out that 3˚ hydrogens are replaced in radical chlorination 5 times faster than 1˚ hydrogens. CH3 H3C CH CH3
+ Cl2
hn
CH3 CH3 + H3C C CH3 H3C CH CH2Cl Cl Obtained in ratio of 35 : 65
Bomination is more "selective". When examine a reaction for bromination, find that 3˚ hydrogens are replaced 1000 times faster than 1˚.
CH3 H3C CH CH3
+ Br2
hn
CH3 H3C C CH3 + Br Obtained in > 99%
CH3 H3C CH CH2Br
Less reactive, more selective (Br2) More reactive, less selective (Cl2) In free radical chlorination get a mixture of products. In bromination, if a 3˚ H present get substitution there over others. 3. Allylic Bromination of Alkenes Using slow generation of Br2 from NBS is presence of light - get substitution rather than addition to the alkene double bond. Br
O
NBS
NBS =
hn, CCl 4
N Br
N-Bromosuccinimide
O
This is radical halogenation but only hydrogens on sp3 carbon adjacent to alkene sp2 carbons are substituted. These are allylic hydrogens.
4
Allylic hydrogens H
H
H Alkyl hydrogens H
H
Vinylic hydrogens
H
Free radical stability Allylic > 3˚ > 2˚ > 1˚ > methyl > vinylic H Br
H
H
Br Br
+
Br
H + Br
Allylic radical is stabilized by resonance. H C
H C H
H C
H
H
C
C H
H
H H
d C
C d C
In a symmetrical alkene such as cyclohexene, either allylic carbons may be substituted and get the same product. Br NBS
KOH
hn, CCl 4
This is a "conjugated diene".
In an unsymmetrical alkene get a mixture of products. Cannot always predict which you will get more of. But can explain experimental data after you examine the
5
reaction and see which product is produced in greater yield. Sometimes two opposing phenomena are at work. NBS
CH3CH2CH2 CH2 CH=CH2
CH3CH2CH2 CH=CH-CH2 Br + CH3 CH2 CH2CHBrCH=CH2
hn
4. Alkyl Halides from Alcohols The most general method of preparing halides is from alcohols. a) With conc H-X R OH
+
H X
R X + HOH X = Cl, Br, I
Best with 3˚ alcohols to 3˚ halides. Primary and secondary are slower with this reagent.
OH
+ HBr
Br
3˚ alcohol
3˚ halide
b) For 2˚ and 1˚ alcohols, use PBr3 (phosphorous tribromide) and SOCl2 (thionyl chloride). OH CH3CH2 CHCH2CH3 OH CH3CH2 CHCCH2CH3 O
Br CH3CH2 CHCH2CH3
PBr3 SOCl2
CH3CH2
Cl CH CCH2CH3 O
With these latter two reagents, one is less likely to get rearranged products. Mechanism will be examined in a later chapter.
Reactions of Alkyl Halides 1. Grignard Reagents 6
Grignard reagents are organometallic compounds that have many uses. We will look at only one here. Others will be examined in later chapters.
R X
anhydrous
+ Mg
R Mg X
ether or THF
X = Cl, Br, I
Bromine and iodine are best (chlorine is slower - less reactive) Fluroides usually do not react. CH3CH2Cl
+
Mg
Br + Mg
Br
+ Mg
anh. ether
CH 3CH2MgCl MgBr
anh. ether
anh. ether
MgBr
Highly polar bond to metal but dipole is reversed from most of what we have seen so far. d-
C
d+ MgX
The carbon is d - and the metal is d +. Carbon in a Grignard reagent reacts as if it were a carbanion –A POWERFUL BASE!. Grignards react with proton donors. Are strong proton acceptors in addition to being nucleophiles. Below are some proton donors that react with Grignard reagents. O H OH
RO
H
R C OH
The reaction with water is shown. An alkane is the product.
7
R NH
d- R d+ Mg
+
X
d+ H d- OH
R
H + MgX(OH)
In preparing a Grignard for some subsequent use, must be very careful in reaction conditions and in the presence of other functional groups in the molecule (other than the halide). Br CH3 CHCH2 CH2CH2OH
Mg
CH3
MgBr CHCH2 CH2CH2OH
NO!
a. Solvent must be anhydrous (NO WATER) b. Functional groups with an active hydrogen cannot be present. (We will see in later chapters that some other groups also cannot be present). 2. Organometallic Coupling Reactions These reactions allow us to make new carbon-carbon bonds, increasing the size of the molecule. CH3CH2CH2 -Br
2Li
CH3CH2CH2 Li +
LiBr
These reagents are both nucleophiles and bases. The preparation of organo lithium compounds from halides works best with primary (1˚) halides.
CH3CH2-Br 2CH3CH2Li
+
CuI
CH3 CH2 Li +
LiBr
(CH3 CH2)2 Cu Li
+
LiI
This part works best with primary halides
Gilman Reagent
From these organolithium compounds we can make a new organometallic called a Gilman reagent. Gilman reagents are used to make new carbon-carbon bonds in coupling reactions. 8
(CH3CH2)2 Cu Li
+
R-I
R-CH2CH3
+ LiI
CH3CH2Cu
This part of synthesis can be done with any kind of halide vinyl,,,,,,,,,,,alkyl,,,,,,,,,,,,,,aryl ,,,,,,,,,,,,,,,,
In this coupling reaction, can use vinyl, aryl or alkyl halides.
Oxidations and reductions in organic chemistry. Oxidation = Gains in bonds of electronegative elements: O, halogen, N, S, etc, and/or loss of bonds to hydrogen. Reduction = Gain in bonds to H and/or loss of bonds to electronegative elements. Carbon (diamond/graphite/buckyballs)
[H] CH4 [O] [H]
H
C
[O]
O
[O]
O OH [H]
H
[H]
C
[O]
[O] H
CH3OH [H]
Where [O] is symbol for oxidation and [H] is symbol for reduction
O C CO2 + H2O HO OH Carbonic acid: In equilibrium with carbon dioxide and water
Br2
Br C-C
Br
H C-C
Br
[O]
C=C
HBr
H2
H C-C Hr
[H]
9
Neither [O] nor [H]
