The Berkeley Review MCAT Organic Chemistry Part 2

308 Pages·2011·44.19 MB·English

by  The Berkeley Review

Organic
Chemistry
Part II
Sections V-VIII
Section V
Carbonyls and Alcohols
Section VI
Carbohydrates
Section VII
Nitrogen Compounds
Section VIII
Organic Chemistry
Laboratory Techniques
BERKELEY
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ERKELEY
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Phone: [phone] (80 0) M CAT-TBR
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Oxygen Containing Compounds
a) Alcohol Properties
Section V b) Alcohol Reactivity
c) Alcohol Spectroscopy
d) Aldehyde and Ketone Properties
e) Aldehyde and Ketone Reactivity
Carbonyls f) Aldehyde and Ketone Spectroscopy
g) Ketals and Acetals
and i. Protecting Groups
h) Carboxylic Acids and Derivatives
Alcohols i. Carboxylic Acids
ii. Esters
by Todd Bennett iii. Lactones
iv. Acid Anhydrides
v. Acid Halides
0 O
vi. Amides
Off
/C\0 Carbonyl Reactivity
RX XCH3 R CH2
a) Attack at Carbonyl Carbon
O O b) Deprotonation of a-Protons
c) Oxidation-Reduction Reactions
C +1
R CH2 R CH2I Name Reactions
O O a) Qrignard Reaction
2more times || b) Aldol Condensation
Off.
/C\ /C\ c) Claisen Condensation
R' 'CH2I ^5~" R CI3
d) Transesterification
O O e) Wittig Reaction
f) Pinacol Rearrangement
Off. g Iodoform Reaction
/c\ + cl3
R OH h) Wolff-Kishner Reaction
o O
Synthetic Logic
C + CI3 ^f=^ C. 0 + HCI3 a) Reactions of Acetoacetic Ester
R OH R O yeUowoil b) Reactions of Malonic Ester
Iodoform Test c) Decarboxylation
d) Protecting Groups
Carbonyl Biochemistry
a) Biological Oxidation-Reduction
b) Biochemical Reagents
BERKELEY
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Carbonyls & Alcohols
Section Goals
Recognize the carbonyl functional groups and types of compounds.
You must be able to recognize functional groups suchas amides, anhydrides, acidhalides, and
°!> especially ketones and aldehydes. You must know which compounds are most reactive towards
substitution (which isbasedon the leaving group strength), and mostelectrophilic (which isbased
on the electron withdrawing or donating capacity of the functional group).
Be able to identify infrared peaks for carbonyl compounds.
Carbonyl compounds will have apeak in the infrared spectrum in the area of 1700± cm'1. This will
mostlikely beuseful whencomparing twocarbonyl compounds, or identifying an unknown carbonyl
compound. You may wish toknow roughly where esters, aldehydes, and ketones fall inthe IR range.
Be able to identify common name reactions involving carbonyl compounds.
© You must recognize common name reactions from carbonyl chemistry. Included inthis group should
* be theAldolcondensation, Grienardreaction, Wittie reaction, and the Claisen reaction. TheAldol
and Claisen reactions have biological significance, because they play a role in select biochemical
pathways such as glycolysis and beta oxidation.
Be able to recognize the acidity of alpha carbons.
The carbon alpha to thecarbonyl can bedeprotonated, ifit hasa proton bonded to it. The pKa ofa
standard ketone is the range 1/± 2. Once deprotonated, an enolate is formed. The enolate has an
equilibrium of its own with the enol structure. The conversion of a ketone into an enol is referred
to as tautomerization.
Be able to identify ketals, hemiketals, acetals and hemiacetals.
Although current accepted nomenclature does notdistinguish between ketals andacetals, youshould
* be aware of the functional group. Acetals and ketalsare best described as "doubleethers." They
play a major role in sugar chemistry and protecting groups in carbonyl synthesis.
Understand the difference between thermodynamic and kinetic enolates.
Thethermodynamic enolate is formed underconditions ofhighertemperature wherethe pathway
ofgreateractivation energymaybe chosen. Thethermodynamic enolateis the moresubstitutedand
thus more stable intermediate which will lead tothe more stable final product. The kinetic enolate
is formed underconditions oflower temperature and greater steric hindrance where thepathway
of lower activation energy must be chosen. The kinetic enolate is the less substituted and thus less
stable intermediate which will lead to the lessstablefinalproduct.
Know the mechanisms for acidic and basic carbonyl reactions.
The mechanism for transesterification ispresent inbiochemistry andorganic chemistry, soit important
that you recognize the steps. Also recognize what catalyst is necessary to carryout the process.
Recognize common oxidizing and reducing agents.
©
a nutshell, oxidation isdefined as thegainofbondstooxygen and/or the lossofbondstohydrogen.
n Oxidizing agentsincludeKMn04and K2Cr207. Reduction is definedas the lossofbonds to oxygen
and/or the gain of bonds to hydrogen. Reducing agents include LiAlH4 and NaBI-14.
Know common reactions by both name and reagents.
The AAMC guide lists a series ofreactions that they expect you toknow byname. Iris a eood idea
tonot only know the general reaction, butalso the mechanism and reaction conditions. Highlights
of this list include the Aldol reaction, the Grignard reaction, the Witting reaction, the iodoform
reaction, transesterification, and the Wolff-Kishner reduction.
Organic Chemistry Carbonyls and Alcohols Introduction
Carbonyls and Alcohols
The carbon-oxygen bond isa major part oforganic and biological chemistry. A
significant part of organic chemistry on the MCAT involves compounds that
contain carbon-oxygen bonds. In the case of carbonyl compounds, the carbon-
oxygen 7C-bond is easily broken to form new bonds to the carbonyl carbon and
subsequently form a new compound. The carbon-oxygen a-bond found in
alcohols and sugars can undergo several reactions, but it is generally not as
reactive as the carbon-oxygen rc-bond. Our goalis to organize the vast multitude
of reactions involving carbonyl compounds and alcohols. Figure 5-1 shows
several types of carbonyl compounds and carbonyl derivatives with which you
should be familiar.
Types of Carbonyl Compounds
0 O
R R R H
Ketone Aldehyde
R'Ov OR* R'Ov OH R'O OR' R'O OH
\/ \/ \/ \/
R H R H R/CVR R/CVR
Acetal Hemiacetal Ketal Hemiketal
O O O O
II II II II
R OH[ R OR' R O R
Carboxylic Acid Ester Acid anhydride
it If If if
.'N. R NH2 R N R'
H
Acid halide Amide Imide
NHPh
/
R R
Lactone Phenylhydrzine derivative Lactam
? If
/c\
R R CHn
Enolate Resonance Forms
Figure 5-1
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OrgSlIllC ChCllllStry Carbonyls and Alcohols Oxygen Containing Compounds
Oxygen containing compounds, because of the highly electronegative nature of
oxygen, are very reactive. Much of organic chemistry revolves around alcohols
and carbonyls, so it is imperative to get a fundamental understanding of their
properties, reactivity,and spectroscopicevidence that supports their existence.
Alcohol Properties
Because of their ability to form hydrogen bonds, alcohols typically have high
boiling points and are generally miscible in water. Alcohols make good solvents
as they are often liquids at room temperature and they have a large range
between their melting and boiling points. Alcohols are hydrophilic, polar
molecules that become less hydrophilic (more lipophilic) as their carbon chain
length increases. The smaller alcohols (three carbons or less) are highly water
soluble, but as the size of the alkyl group increases, their water solubility
decreases. As with all compounds, their physical properties vary with mass and
branching, as well as the position of the hydroxyl group. As the molecular mass
increases, the boiling point increases, but the effect on the melting point is less
clear. As the branching increases, the boiling point decreases. Table 5-1 shows
the physical properties of several alcohols, from which the effects of mass,
branching, and positioning of thehydroxyl group on the physical properties can
be ascertained.
Water
Isomer IUPAC Name Boiling Melting Density
(Common Name) Point Point (g/mL) Solubility
(g/lOOmL)
CH3OH Methanol 64.6°C -98°C 0.791 High
H3CCH2OH Ethanol 78.4°C -115°C 0.789 High
H3CCH2CH2OH 1-Propanol (n-Propanol) 97.2°C -127°C 0.804 High
(H3Q2CHOH 2-Propanol (i-Propanol) 82.3°C -90°C 0.786
High
H3C(CH2)3OH 1-Butanol (w-Butanol) 117.3C -90°C 0.810 8.2
H3CCH(OH)CH2CH3 2-Butanol (sec-Butanol) 99.6°C -115°C 0.806 12.8
(H3C)2CHCH2OH 2-Methyl-l-propanol (f-Butanol) 107.7°C -122°C 0.802
11.3
(H3Q3COH 2-Methyl-2-propanol (f-Butanol) 82.0°C 24°C
0.789 High
H3C(CH2)4OH 1-Pentanol (n-Pentanol) 137.6°C -79°C
0.814 2.1
H3CCH(OH)CH2CH2CH3 2-Pentanol 119.3°C 0.809 5.0
(H3CCH2)2CHOH 3-Pentanol 115.9°C 0.815
5.6
H3C(CH2)4CH3 1-Hexanol (n-Hexanol) 157.5°C 0.814
0.8
C6HnOH Cyclohexanol 161.5°C 0.956 2.1
H3C(CH2)6CH2OH n-Octanol 194.7°C 0.817 1 0.3
T able 5-1
Copyright©by The Berkeley Review The Berkeley Review
OrgaiUC ChemiStry Carbonyls and Alcohols Oxygen Containing Compounds
Example 5.1
Whattype of alcohol is the following molecule?
HiC CH„
HO-
A. Primary alcohol
B. Secondary alcohol
C. Tertiary alcohol
D. Phenol
Solution
The compound has the alcohol functional group attached to a carbon that is
bonded to two other carbons. This is definedas a secondary alcohol, so the best
answer is choice B.
Alcohol Reactivity
Alcohols are nucleophilic reagents in organic chemistry. They are not good
nucleophiles in their protonated (neutral)state, but they can be deprotonated and
converted into their anion (alkoxide) form under basic conditions. Because
alkoxides (the deprotonated form of the alcohol) are strong bases, they are not
the ideal nucleophile, but they are generally better than alcohols. Alcohol
chemistry also involves oxidation into a carbonyl as we shall see later in this
section. Alcohols are commonly formed from the reduction of carbonyls, which
we shall also postpone for the moment. The common reactions to form and
consume alcohols that do not involve carbonyl compounds center around
nucleophilic substitution. Figure 5-2 shows nucleophilic substitution reactions
that convert alkyl halides into alcohols. Figure 5-3 shows nucleophilic
substitution reactions that convert alcohols into alkyl halides.
Alkyl halides to alcohols
R R
OH + X
h*%/ x ~2~~^ H*y
H H
R' R'
\ 1. RCO," / „ . „^ TT
R»';?-Br 2.0H-(ac,)» H°~V"R + + 2
H H
R" R"
„„t.^—X 1 • t,ii»»^— OH +HX
Rv / acetone Rx /
R' R'
Figure 5-2
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OrCJ£UllG ChCHllStry Carbonyls and Alcohols Oxygen Containing Compounds
Alcohols to alkyl halides
O
R « R
/s^
Cl
,^-oh S ^—Cl Retention
H^
H H
R' R'
PBr,
OH Br-i Inversion
r^;
h
H H
R" R"
OH ^L^. Br Racemization
R^h r^;
h
K R'
Figure 5-3
Spectroscopic Evidence for Alcohols
Alcohols can be detected using either infrared or NMR spectroscopy. In IR
spectra, hydroxyl groups present a distinct absorbance between 3200 and 3500
cm"1 that is medium in intensity and broad due to hydrogen bonding. In
XHNMR spectra, hydroxyl groups present asignal between 1and 5ppm that is
broaddue tohydrogen bonding, although the broadness varies with thesolvent.
They have no definite 6-value (it varies with concentration and solvent). The
peak slowly disappears with the addition of D2O to the NMR tube. The OH
group does notcouple well, sowerarely consider splitting patterns foralcohols.
Figure 5-4 shows the 1HNMR spectrum for 2-propanol in carbon tetrachloride
solvent. Figure 5-5 shows the IR spectrum for 2-propanol obtained neat onsalt
plates.
H OH
6H
H,C CH,
1H
1H
1
3.0 ppm 2.0 1.0
Figure 5-4
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Ur£J£UllC t/llCllllStry Carbonyls and Alcohols Oxygen Containing Compounds
PTVl
1392 cm-'
1455 cm-1 & 1365 cm-'
2984 cm
Figure 5-5
Aldehyde and Ketone Properties
Because aldehydes and ketones do not form hydrogen bonds, they typically have
boiling points only slightly higher than alkanes of equal mass. Because of the
polarity of the carbonyl bond, they are slightly miscible in water. Aldehydes and
ketones are aprotic, polar molecules that become less hydrophilic as their carbon
chain length increases. The smaller aldehydes and ketones (three carbons or less)
are generally water soluble but as the size of the alkyl group increases, their
water solubility decreases. Table 5-2 shows the physical properties of several
aldehydes and ketones, from which the effects of mass, branching, and
positioning of the carbonyl group on the physical properties can be ascertained.
Water
IUPAC Name Boiling Melting
Isomer Solubility
(Common Name) Point Point
(g/lOOmL)
HCHO Methanal (Formaldehyde) -21°C -92°C High
H3CCHO Ethanal (Acetaldehyde) 21°C -121°C Infinite
H3CCH2CHO Propanal (Propionaldehyde) 49°C -81°C 16.3
H3C(CH2)2CHO Butanal (n-Butyraldehyde) 76°C -99°C 6.8
H3C(CH2)3CHO Pentanal 103°C -92°C 3.3
H3C(CH2)4CHO Hexanal 128°C -56°C 2.1
C6H5CHO Benzaldehyde 178°C -26°C 0.3
H3CCOCH3 Propanone (Acetone) 56°C -94°C Infinite
H3CCOCH2CH3 Butanone (Ethyl methyl ketone) 80°C -86°C 25.6
H3CCO(CH2)2CH3 2-Pentanone 102°C -78°C 5.7
(H3CCH2)2CO 3-Pentanone 1018C -41'C 4.9
H3CCO(CH2)3CH3 2-Hexanone 128°C -55°C 1.6
H3CCH2CO(CH2)2CH3 3-Hexanone 124°C 1.3
H3CCOCH2CH(CH3)2 4-Methyl-2-Pentanone 119°C -85°C 1.9
C6Hi0O Cyclohexanone 156°C °C 2.2
C6H5COCH3 Acetophenone 202°C 21°C Insoluble
Table 5-2
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OrCJcllllC l^IlCllllStry Carbonyls and Alcohols Oxygen Containing Compounds
Example 5.2
What is the IUPACname for the following compound?
OH
r H
O
A. l-Aldo-4-pentanol
B. 4-Hydroxypentanal
C. 5-Oxo-2-pentanol
D. 2-Hydroxypentaldehyde
Solution
The longest chain isfive carbons and the highest priority functional group is the
aldehyde. The functional group with the most oxidized carbon receives the
highest priority according toIUPAC convention. For naming aldehydes, the"e"
is dropped from the alkane chain of thesamelengthand an "al" suffix is added.
This makes the compound pentanal, which makes choice B correct. The OH is
named hydroxy as a substituent.
Aldehyde and Ketone Reactivity
Aldehydes consist ofa carbonyl with a hydrogen bonded to the carbonyl carbon
along with either an alkyl group or in the case of formaldehyde, a second
hydrogen. Ketones consist of a carbonyl group with two alkyl substituents
attached. The chemistry occurs primarily at the electrophilic carbonyl center.
Aldehydes and ketones are reactive with most nucleophiles, but not by a
traditional nucleophilic substitution mechanism. Once a nucleophile attacks a
carbonyl carbon, it forms a four-ligand intermediate with a negative charge on
oxygen known as a tetrahedral intermediate. This intermediate will be shown in
the mechanism of many carbonyl reactions in this section. The chemistry of
aldehydes is similar to the chemistry of ketones except that analdehyde can be
oxidized into a carboxylic acid while ketones cannot be oxidized easily.
Oxidation in carbonyl chemistry can be viewed as either the gain ofbonds to
oxygen orthe loss of bonds to hydrogen. We shall thoroughly address carbonyl
reactions throughout this section.
Spectroscopic Evidence for Aldehydes and Ketones
Aldehydes have infrared absorbances inthe 1720 cm"1 to1740 cm-1 range. They
are unique in the IR from other carbonyls due to two medium C-H stretches
around2700 cm-1 and 2900 cm-1. Ketones haveinfrared absorbances in the1710
cm-1 to 1725 cm-1 range. In *HNMR, aldehyde hydrogens are found between 9
and10 ppm, which makes aldehydes easy toidentify via *HNMR. Ketones and
aldehydes each have alpha protons which fall in the 2.0 to 2.5 ppm range in
!HNMR. Figure 5-6 shows the *HNMR spectrum for butanone in carbon
tetrachloride solvent. Figure 5-7 shows the IR spectrum for butanal obtained
neat on salt plates.
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