Upload
felicity-harvey
View
223
Download
3
Tags:
Embed Size (px)
Citation preview
CH-1Organic Chemistry-2
Prepared By
Prof Dr. Abdelfattah Haikal & Dr. Khalid Ahmad Shadid
Islamic University in Madinah
Department of Chemistry
AlcoholsAlcohols from Carbonyl CompoundsOxidation-Reduction & Organometallic Compounds
OH OH OH
Structure & Nomenclature Alcohols have a hydroxyl (–OH) group
bonded to a saturated carbon atom (sp3 hybridized)
1o 2o 3o
Ethanol 2-Propanol(isopropylalcohol)
2-Methyl-2-propanol
(tert-butyl alcohol)
OHOH
OH
2-Propenol(allyl alcohol)
2-Propynol(propargyl alcohol)
Benzyl alcohol
Phenols
• Compounds that have a hydroxyl group attached directly to a benzene ring
OH
Phenol
OH
4-Methylphenol
OH
3-Chlorophenol
Cl
H3C
Ethers
• The oxygen atom of an ether is bonded to two carbon atoms
Diethyl ether tert-Butyl methyl ether
Divinyl ether
OO
CH3
O O
Ethyl phenyl ether
Physical Properties ofAlcohols and Ethers
Ethers have boiling points that are roughly comparable with those of hydrocarbons of the same molecular weight (MW)
Alcohols have much higher boiling points than comparable ethers or hydrocarbons
For example
O
Diethyl ether
(MW = 74)
b.p. = 34.6oC
Pentane
(MW = 72)
b.p. = 36oC
OH
1-Butanol
(MW = 74)
b.p. = 117.7oC
Alcohol molecules can associate with each other through hydrogen bonding, whereas those of ethers and hydrocarbons cannot
Water solubility of ethers and alcohols
• Both ethers and alcohols are able to form hydrogen bonds with water
• Ethers have solubilities in water that are similar to those of alcohols of the same molecular weight and that are very different from those of hydrocarbons
• The solubility of alcohols in water gradually decreases as the hydrocarbon portion of the molecule lengthens; long-chain alcohols are more “alkane-like” and are, therefore, less like water
Physical Properties of Ethers
Dimethyl ether
Diethyl ether
Diisopropyl ether
1,2-Dimethoxyethane
CH3OCH3
CH3CH2OCH2CH3
(CH3)2CHOCH(CH3)2
CH3OCH2CH2OCH3
-138
-116
-86
-68
-24.9
34.6
68
83
O
O
(DME)
Oxirane
Tetrahydrofuran (THF)
-112
-108
12
65.4
Name Formula mp(oC)
bp (oC)(1 atm)
Physical Properties of Alcohols
Methanol
Ethanol
Isopropyl alcohol
tert-Butyl alcohol
Hexyl alcohol
Cyclohexanol
Ethylene glycol
CH3OH
CH3CH2OH
CH3CH(OH)CH3(CH3)3COH
CH3(CH2)4CH2OH
-97
-117
-88
25
-52
24
-12.6
64.7
78.3
82.3
82.5
156.5
161.5
197
inf.
inf.
inf.
inf.
0.6
3.6
inf.
OH
HOOH
Name Formula mp(oC)
bp (oC)(1 atm)
*
* Water solubility (g/100 mL H2O)
Diethyl EtherDiethyl Ether
Diethyl ether is a very low boiling, highly flammable liquid
Most ethers react slowly with oxygen by a radical process called autoxidation to form hydroperoxides and peroxides
Step 1
O O C OR'
H
O O H+ COR'
+
Step 2
C OR'
OO
COR'
+ O2
Hydrogen abstractionadjacent to the ether oxygen
occurs readily
Step 3a
C OR'
H
+ COR'
+C OR'
OO
C OR'
OOH
orStep 3b
+ COR'
C OR'
OO
R'O C OO C OR'
Hydroperoxides and peroxidescan be explosive
A hydroperoxide
A peroxide
Synthesis of Alcohols from Alkenes
Acid-catalyzed Hydration of Alkenes
C CH
H2OC C
OHH
C C
OH
H
H
C C
H
H⊕
H2O
H2O
Reactions of Alcohols The reactions of alcohols have mainly to do
with the following:• The oxygen atom of the –OH group is
nucleophilic and weakly basic• The hydrogen atom of the –OH group is
weakly acidic• The –OH group can be converted to a
leaving group so as to allow substitution or elimination reactions
OH
C–O & O–H bonds of an
alcohol are polarized
Protonation of the alcohol converts a poor leaving group (HO⊖) into a good one (H2O)
C O+ H
H
C O H H A A+
alcohol strongacid
protonatedalcohol
Once the alcohol is protonated substitution reactions become possible
C O H
H
Nu + CNu + O H
H
protonatedalcohol
SN2
The protonated –OHgroup is a good leavinggroup (H2O)
Alcohols as Acids
Alcohols have acidities similar to that of water
pKa Values for Some Weak Acids
Acid pKa
CH3OH 15.5
H2O 15.74
CH3CH2OH 15.9
(CH3)3COH 18.0
Relative Acidity
H2O > ROH > > H2 > NH3 > RHRC CH
H2O & alcohols are thestrongest acids in this series
Increasing acidity
Relative Basicity
R > NH2 > H > > RO > HORC C
HO⊖ is the weakestacid in this series
Increasing basicity
Conversion of Alcohols into Alkyl Halides
• HX (X = Cl, Br, I)• PBr3
• SOCl2
R OH R X
OH Clconc. HCl
25oC+ HOH
(94%)
Examples
OH Br
(63%)
PBr3
Alkyl Halides from the Reactionof Alcohols with HydrogenHalides
The order of reactivity of alcohols• 3o
The order of reactivity of the hydrogen halides
• HI > HBr > HCl (HF is generally unreactive)
R OH R XHX+ + H2O
> 2o > 1o < methyl
Mechanisms of the Reactions ofAlcohols with HX
Secondary, tertiary, allylic, and benzylic alcohols appear to react by a mechanism that involves the formation of a carbocation
Step 1
H O H
HO
H + O H
HO
H +
Hfast
Step 2
OH
H
O H
H
+
slow
Step 3
+ ClClfast
Primary alcohols and methanol react to form alkyl halides under acidic conditions by an SN2 mechanism
+X R C O H
H
H
H
protonated 1o alcohol
or methanol
RC
H
H
X O H
H
+
(a goodleaving group)
Reaction of alcohols with SOCl2
• SOCl2 converts 1o and 2o alcohols to alkyl chlorides
• As with PBr3, the reaction does not involve the formation of a carbocation and usually occurs without rearrangement of the carbon skeleton (especially if the temperature is kept below 0°C)
• Pyridine (C5H5N) is often included to promote the reaction
O
Structure of the Carbonyl Group
Carbonyl compounds
O
R HAldehyde Ketone
O
R R'
Carboxylic acid
O
R OH
Ester
O
R OR'
Amide
O
R NR'
R"
StructureStructureThe carbonyl carbon atom is sp2 hybridized; thus it and the three groups attached to it lie in the same plane. The bond angles between the three attached atoms are what we would expect of a trigonal planar structure; they are approximately 120o.
The bonding molecular orbital of formaldehyde (HCHO). The electron pair of the bond occupies both lobes.
Polarization and resonance structure
O
C
O
C
The more electronegative oxygen atom strongly attracts the electrons of both
the bond and the bond, causing the carbonyl group to be highly polarized;
the carbon atom bears a substantial positive charge and the oxygen atom bears
a substantial negative charge.
1/31/2015
30There is a large dipole moments associated with carbonyl compounds.
Reactions of Carbonyl Compounds with Reactions of Carbonyl Compounds with NucleophilesNucleophiles
Nu
O
C
nucleophilic
addition
O
CNu
One of the most important reactions of carbonyl compounds is one in which the carbonyl compound undergoes nucleophilic addition. The carbonyl group is susceptible to nucleophilic attack because, the carbonyl carbon bears a partial positive charge.
As the reaction takes place, the carbon atom undergoes a change in its geometry and its hybridization state. It goes from a trigonal planar geometry and sp2 hybridization to a tetrahedral geometry and sp3 hybridization.
Two important nucleophiles:●Hydride ions (from NaBH4 and
LiAlH4)●Carbanions (from RLi and RMgX)
O
CR H
OH
R HH
oxidation
reduction
1o alcohol aldehyde
[O]
[H]
Primary alcohols can be oxidized to aldehydes, and aldehydes can be reduced to alcohols.
Oxidation-Reduction Reactions in Organic Chemistry
Reduction of an organic molecule usually corresponds to increasing its hydrogen content or decreasing its oxygen content
carboxylicacid
reduction
[H] O
R H
O
R OHaldehyde
oxygen contentdecreases
reduction
[H] OH
R H
O
R HH
hydrogen contentincreases
The opposite reaction of reduction is oxidation.
Oxidation involves Increasing the oxygen content of an organic
molecule or decreasing its hydrogen content is oxidation
OH
R HH
O
R OH
O
R H
[O]RCH3
[H]
[O]
[H]
[O]
[H]
lowestoxidation
state
highestoxidation
state
Oxidation of an organic compound may be more broadly defined as a reaction that increases its content of any element more electronegative than carbon
[O]
[H]
[O]
[H]
[O]
[H]Ar CH3 Ar CH2Cl Ar CHCl2 Ar CCl3
Alcohols by Reduction of Carbonyl Compounds
R OH
H H(1o alcohol)
[H]
R R'
O
R R'
HO H
H
R O
[H]
[H]OH
R O
[H]OR'
R O
Primary and secondary alcohols can be synthesized by the reduction of a variety of com pounds that contain the carbonyl group.
(2o alcohol)
Carboxylic acid
Ester
Aldehyde
Ketone
Lithium Aluminum Hydride
LiAlH4 (LAH)● Not only nucleophilic, but also very basic● Reacts violently with H2O or acidic
protons (e.g. ROH)● Usually reactions run in ethereal solvents
(e.g. Et2O, THF)● Reduces all carbonyl groups
1/31/2015
38
Reductions of carboxylic acids are the most difficult, but they can be accomplished with the powerful reducing agent lithium aluminum hydride (LiAlH4, abbreviated LAH). It reduces carboxylic acids to primary alcohols in excellent yields.
Examples
O
R OH
OH
R HH
1. LiAlH4, Et2O
2. H+, H2O(1)
O
R OR'
1. LiAlH4, Et2O
2. H+, H2O(2)
OH
R HH
+ HOR'
O
R H
OH
R HH
1. LiAlH4, Et2O
2. H+, H2O(3)
Mechanism
O
R OR'
H
Al HH
H
+
O
OR'R
HO
R HR'O +
H
Al HH
HO
RH
H
OH H
OH
RH
H
Esters are reduced to 1o alcohols
Sodium BorohydrideSodium Borohydride
NaBH4
● less reactive and less basic than LiAlH4
● can use protic solvent (e.g. ROH)● reduces only more reactive carbonyl
groups (i.e. aldehydes and ketones) but not reactive towards esters or carboxylic acids
Aldehydes and ketones can also be reduced to alcohols by hydrogen and a metal catalyst, by sodium borohydride (NaBH4)
Examples
Mechanism (Animation)
O
R R'
H
B HH
H
+
O
R'R
H
OH HOH
RH
R'
Aldehydes are reduced to 1° alcohols & ketones are reduced to 2° alcohols
1/31/2015
44
A Mechanism for the A Mechanism for the ReactionReaction
Overall Summary of LiAlH4 and NaBH4 Reactivity
O
R O<
O
R OR'
O
R R'<
O
R H<
ease of reduction
Reduced by NaBH4
Reduced by LiAlH4
1/31/2015
46
Which reducing agent, LiAIH4 or NaBH4 would you use to carry out the following transformations?
ProblemProblem
5. Organometallic Compounds Compounds that contain carbon-metal bonds
are called organometallic compounds
C M
primarily ionic(M = Na or K)
C : M
(M = Mg or Li)
C M
primarily covalent(M = Pb, Sn, Hg or Tl)
Organometallic compounds of lithium and magnesium are of great importance in organic synthesis. Their carbon-metal bonds have considerable ionic character. The carbon atoms that is bonded to the metal atom of an organolithium or organomagnesiurn compound is a strong base and powerful nucleophile.
Preparation of Organomagnesium Compounds
Organomagnesium halides were discovered by the French chemist Victor Grignard in 1900. Grignard received the Nobel Prize for his discovery in 1912, and they are now called Grignard reagents in his honor. Grignard reagents have great use in organic synthesis.
Grignard reagents are usually prepared by the reaction of an organic halide and magnesium metal in an ether solvent.
Order of reactivity of RX● RI > RBr > RCl
THF+ Mg
Br MgBr
Example
1/31/2015
50
Reactions with Compounds Containing Acidic Hydrogen Atoms
Grignard reagents and Organolithium compounds are very strong bases. They react with any compound that has a hydrogen attached to an electronegative atom such as oxygen, nitrogen, or sulfur.
Preparation of Organomagnesium Compounds
Reactions of Organolithium andOrganomagnesium Compounds
Reactions with Compounds Reactions with Compounds Containing Acidic HydrogenContaining Acidic HydrogenAtomsAtoms
RMgX ~ R:MgX RLi ~ R:Li
Grignard reagents are very strong bases
R MgX H Y+
(or RLi) (Y = O, N or S)
++ XR H Y Mg2+ +
Examples● As base
CH3OH+
MgBr
+ Mg2+ + Br
+ CH3O(2)
CH3MgBr + H2O + HOH3C H(1)
+ Mg2+ + Br
Examples● As base
CH3OH+
MgBr
+ Mg2+ + Br
+ CH3O(2)
CH3MgBr + H2O + HOH3C H(1)
+ Mg2+ + Br
Examples● As base
(3) H + H3C MgBr
MgBr H CH3+
A good method for the preparationof alkynylmagnesium halides
Reactions of Grignard Reagents with Epoxides (Oxiranes)
Not only are Grignard reagents strong bases, they are also powerful nucleophiles. They attack at a saturated carbon when they react with oxiranes to give primary alcohols.
The nucleophilic alkyl group of the Grignard reagent attacks the partially positive carbon of the oxirane ring. Because it is highly strained, the ring opens, and the reaction leads to the salt of a primary alcohol.
Via SN2 reaction
OR RO
H , H2O
ROH
(1o alcohol)
Alcohols from Grignard Reagents
Grignard additions to carbonyl compounds are especially useful because they can be used to prepare primary, secondary, or tertiary alcohols.
1. Grignard Reagents React with Formaldehyde to Give a Primary Alcohol.
2. Grignard Reagents React with All Other Aldehydes to Give Secondary Alcohols
3. Grignard Reagents React with Ketones to Give Tertiary Alcohols
4. Esters React with Two Molar Equivalents of a Grignard Reagent to Form Tertiary Alcohols.
The product is a tertiary alcohol with two identical alkyl groups, groups that correspond to the alkyl portion of the Grignard reagent
R = alkyl, R’ = H (higher aldehydes) (Animation) ● 2o alcohol
O
R' HMgXR +
higheraldehyde
O MgX
RH
R'
OH
RH
R'
H3O+
2o alcohol
R, R’ = alkyl (ketone)● 3o alcohol
O
R' R"MgXR +
ketone
O MgX
RR"
R'
OH
RR"
R'
NH3ClH2O
3o alcohol
1/31/2015
61
GOOD GOOD LUCKLUCK
1/31/2015
62