| Section |
Learning Objectives |
| 1.1, 1.2 |
Note the pervasive relevance of organic chemistry to life and society. |
| 1.3 |
Understand molecular and empirical formulas. Know valences for C, H,
N, O, halogens, S. Learn bonding arrangements for the above elements. Understand
constitutional isomers and connectivity. |
| 1.4 |
Know the octet rule and ramifications thereof. Understand ionic and
covalent bonds and electronegativity trends. |
| 1.5 |
Be able to draw proper Lewis structures for neutral and ionic species. |
| 1.6 |
Note some exceptions to the octet rule. |
| 1.7 |
Be able to calculate formal charge on any atom and determine overall
ionic charge. |
| 1.8 |
Understand essential principles of resonance and be able to draw resonance
structures for simple structures where resonance is possible. |
| 1.9 |
Understand wave characteristics (phase interactions) leading to reinforcement
, and interference. Accept the general relevance of wave properties to
atomic structure. |
| 1.10 |
Understand interpretation of the square of the wave function (psi2)
as indicating a region of space where probability of finding an electron
is high. Learn the three dimensional shapes and orientations of s and p
orbitals derived from wave functions. Be able to draw proper valence electron
configurations for C, N, O, and halogens. |
| 1.11 |
Understand the derivation of a specific number of molecular orbitals
from combinations of a given number of atomic orbitals. |
| 1.12 |
Be able to apply electron configurations and the principle of orbital
hybridization to predict the structure of sp3, sp2,
and sp hybridized atoms. Understand the 3-D arrangement of atoms
in an alkane. Understand the origin of sp3 hybridization
through electron promotion and hybridization. Know unequivocally
the structure of an sp3 hybridized carbon atom and the
orbital representation of the its sigma bonds. Understand that rotatioin
can occur about a single bond. |
| 1.13 |
Understand the 3-D arrangement of atoms that are part of an alkene
double bond. Understand the origin of sp2 hybridization
through electron promotion and hybridization. Know unequivocally the orbital
structure of an sp2 hybridized atom and the orbital representation of a
pi bond with a sigma bond framework. Understand the ramifications of restricted
rotation about pi bonds and the potential for cis-trans isomerism, as compared
to free rotation about sigma bonds. |
| 1.14 |
Understand the 3-D arrangement of atoms that are part of an alkyne
triple bond. Understand the origin of sp orbitals through
hybridization and know the orbital structure of an sp hybridized
atom. Understand the overlap of adjacent p orbitals from sp hybridized
carbon atoms leading to the orthogonal relationship of the two pi bonds
in an alkyne. |
| 1.15 |
Use this section to unify your understanding of quantum mechanics concepts
discussed earlier. |
| 1.16 |
Be able to use the VSEPR model to predict tetrahedral, trigonal planar,
and linear molecular geometries for various examples. |
| 1.17 |
Gain unquestionable proficiency in representing organic molecules in
their dash, condensed, bond- line, and three-dimensional (dash-wedge) structural
formulas. |
Key Terms and
Concepts |
Use the Key Terms and Concepts list as a self-test for understanding
of these items. |
Assigned Problems: 1a,b,c,e,h,i, 2bcde, 3, 4, 6, 8cdef, 9, 10, 11, 12,
13, 14, 15, 16, 17, 18b,d, 20, 21, 23, 24, 31, 32
| Section |
Learning Objectives |
| 2.1 |
Note that organic compounds are organized into families according to
their functional group, and that infrared spectroscopy is used to detect
functional groups. |
| 2.2 |
Understand the structural meaning of the terms hydrocarbon, alkanes,
alkenes, alkynes, aromatic, saturated, and unsaturated. Gain a 3-D sense
of the structure of alkanes based on their hybridization and bonding. |
| 2.3, 2.4 |
Be able to apply the principles of electronegativity and bond
polarization for prediction of the overall polarity or lack thereof in
any given molecule. |
| 2.5 |
Understand what alkyl groups are. Know the names and be able to draw
formulas for all alkyl ("R") groups of three carbons or fewer. Understand
the notion of a functional group. Know the structural meaning of the names
and shorthand representations for the phenyl and benzyl groups. |
| 2.6 |
Be able to write the general formulas of 1o (primary), 2o
(secondary), and 3o (tertiary) alkyl halides (using R groups)
and identify real examples of each type. |
| 2.7 |
Be able to write the general formulas of 1o (primary), 2o
(secondary), and 3o (tertiary) alcohols (using R groups) and
identify examples of each type in a real molecule. |
| 2.8 |
Be able to write the general formula of an ether and identify the ether
functional group in real examples. |
| 2.9 |
Be able to write the general formulas of 1o (primary), 2o
(secondary), and 3o (tertiary) amines (using R groups) and identify
examples of each type in a real molecule. |
| 2.10 |
Know the 3-D structure and hybridization of the carbonyl group. Be
able to write the general formulas of aldehydes and ketones and identify
both functional groups in real examples. |
| 2.11 |
Be able to write the general formulas of carboxylic acids, amides,
and esters and identify these functional groups in real examples. |
| 2.12 |
Be able to write the general formula for a nitrile and to identify
this functional group in real examples. |
| 2.13 |
Know the dash and all condensed structural formula representations
for the above functional groups and be able to draw every one from memory.
Not the summary inside the front cover and in Table 2.3. |
| 2.14, 2.14 A-F |
Know the various types of intermolecular forces that are possible and
understand their influence on physical properties (such as mp, bp and solubility)
for a given molecule. |
| 2.15 |
Note the summary of attractive electric forces in Table 2.6. |
| 2.16 |
Understand that atoms and groups of atoms vibrate about the covalent
bonds that connect them. Molecular vibrations can be thought of as balls
(atoms) connected by springs (bonds) oscillating at frequencies in the
infrared region specific to the types of bonds and atoms involved. Begin
to use IR spectra for functional group identification (assuming a frequency
chart is provided, e.g. Table 2.7). |
| 2.16A |
Recognize 3000 cm-1 as the "dividing line between sp2
(3200-3000 cm-1) and sp3 (3000-2800 cm-1)
carbon-hydrogen stretches. Be able to use an IR spectrum to infer the presence
or absence in a molecule of these respective types of C-H bonds. |
| 2.16B |
Be able to use IR spectra to infer the presence or absence of various
functional groups (with the aid of a frequency table like Table 2.7). Understand
this use as probably the most important application of IR spectroscopy
in structure elucidation. |
Key Terms and
Concepts |
Use the Key Terms and Concepts list as a self-test for understanding
of these items. |
Assigned Problems: 1, 2, 3, 4, 5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,
19, 20, 22, 24, 25, 26, 27, 28, 33, 34, 39
| Section |
Learning Objectives |
| 3.1 |
Note the general changes in structure accompanying substitution, addition,
elimination, and rearrangement reactions. From the "Mechanism of Reactions"
box, understand the concept of a mechanism as a stepwise description of
events in a chemical reaction |
| 3.1A |
Understand that cleavage of a bond to a carbon could conceivably occur
by in three ways: homolytically (to form a radical), or heterolytically
with the carbon either keeping or losing both electrons of the bond (to
form a carbanion or carbocation, resp.) Understand the general meaning
of heterolytic and homolytic bond cleavage. |
| 3.2A |
Review concepts of Bronsted-Lowry Acids and Bases. |
| 3.2B |
Understand Lewis acids and bases as generally applicable to acid base
theory. Be able to classify compounds as Lewis acids or bases, especially
with regard to examples involving organic compounds. |
| 3.2C |
Note the importance of the attraction of opposite charges. Be
able to interpret an electrostatic potential map as an illustration of
charge distribution. |
| 3.3 |
Know the general structure of a carbocation and carbanion, Learn the
basic definition/character of nucleophiles and electrophiles. |
| 3.4 |
Understand the precise use of the double-barbed curved arrow and be
able to draw them appropriately and with accurate meaning. |
| 3.5 |
Understand the mathematical derivation of Ka and pKa. Know the significance
of both Ka and pKa regarding acid (and conjugate base) strength. Be able
to write the conjugate base or conjugate acid from any acid or base, respectively,
and the corresponding acid or base from the respective conjugate . |
| 3.6 |
Be able to use Ka or pKa values to predict the direction of an acid-base
reaction. |
| 3.7 |
Understand the influences of bond strength (to the acidic hydrogen),
electronegativity, hybridization, and inductive effects on acidity. |
| 3.8 |
Know the meaning of endothermic, exothermic and enthalpy as applied
to energy changes in chemical reactions. |
| 3.9 |
Understand the relationship of a positive or negative value of deltaGo
to the position of equilibrium fo a reaction. |
| 3.10 |
Know the relative acidities of carboxylic acids and alcohols. |
| 3.11 |
Recognize the ability of protic solvents to solvate the anions formed
upon ionization of an acid. |
| 3.12 |
Understand the capacity of organic compounds containing oxygen to act
as bases and engage in proton transfer reactions. |
| 3.13 |
Note the format and stepwise detail in this example of a mechanism. |
| 3.14 |
Understand the need for solvents other than water when bases stronger
than hydroxide ion are used (understand the leveling effect of water
in these cases). Begin to recognize some exceptionally strong bases (e.g.
NaNH2, NaH, and alkyllithium reagents (RLi). |
| 3.15 |
Understand the ability to introduce deuterium and tritium by acid-base
reactions. |
Key Terms and
Concepts. |
Use the Key Terms and Concepts list as a self-test for understanding
of these items. |
Assigned Problems: 1ac, 2, 3, 5, 7, 9, 10, 11acd, 12, 13abef, 15, 16, 17,
18, 19, 20, 22, 24, 25abde, 29, 31, 32, 38
| Section |
Learning Objectives |
| 4.1 |
Recognize petroleum as the primary natural source of alkanes and aromatic
hydrocarbons. Know the general formulas for an alkane and cycloalkane. |
| 4.2 |
Know the general three-dimensional structure of alkanes, based on the
appropriate hybridization state of carbon, regardless of the type of formula
presented. Understand the structural meanings as pertains to alkanes
of the designations "straight-chain" (or unbranched) and branched. Recall
that constitutional isomers have different physical properties. |
| 4.3, 4.3A-F |
Learn the IUPAC names of alkanes through C20. Learn all
the alkyl group names from C1 through C4. Be able
to apply the IUPAC rules for naming branched chain alkanes. Learn the names
of branched alkyl groups through C5. including the meaning of
prefixes iso-, sec-, tert-. Be able to classify hydrogens as 1o,2o,
or 3o. Be able to name alkyl halides and alcohols using the
IUPAC system. |
| 4.4 |
Be able to name monocyclic alkanes (section 4.4A). Read section 4.4B
for interest. |
| 4.5 |
Be able to correctly apply the IUPAC nomenclature rules to the naming
of any alkene or cycloalkene. Be able to recognize vinyl and allyl groups
by their respective substructures. |
| 4.6 |
Be able to correctly name any alkyne using the IUPAC system. |
| 4.7 |
Recognize the trends in mp and bp among hydrocarbon homologs. Know
the general density and solubility properties of alkanes and cycloalkanes,
as compared to water. |
| 4.8 |
Be able to perform conformational analyses on simple alkanes using
Newman projections to draw the various conformation. Recognize a given
conformation as being staggered or eclipsed. |
| 4.9 |
Understand the significance of torsional strain regarding conformational
anyalysis. Recognize a given conformation as being anti or gauche, as well
as staggered and eclipsed. |
| 4.10 |
Know the relative order of stability for cycloalkanes from cyclohexane
to cyclopropane. Disregard heats of combustion (section 4.8B) unless interested
in further explanation. |
| 4.11 |
Understand the influence of angle and torsional strain on the overall
ring strain in cyclopropane and cyclobutane, as compared to cyclopentane
and cyclohexane. |
| 4.12 |
Be able to recognize and draw clearly the boat and chair conformations
of cyclohexane, especially the chair, showing correct 3-D perspective.
Be able to draw a Newman projection for cyclohexane, viewed along any pair
of C-C bonds. |
| 4.13 |
Learn to identify the axial and equatorial positions on the chair conformation
of cyclohexane. Be able to draw cyclohexane so that axial and equatorial
positions of substituents are absolutely unambiguous. Understand
the origin of 1,3-diaxial interactions and the basis for the relatively
greater stability of chair conformations with substituents in equatorial
orientations. Learn to depict a chair-chair conformational ring flip with
accurate drawings showing the changes in axial and equatorial orientations
of groups. |
| 4.14 |
Understand the possibility for cis and trans stereoisomers in disubstituted
cycloalkanes. Be able to draw both the unrealistic "flat" ring structures
(e.g. pp.165) and realistic chair conformational structures for
disubstituted cyclohexanes (e.g. pp. 165 - 167). Correctly place
cis or trans groups in axial or equatorial orientations, depending on the
preferred, lowest energy conformation for the chair. |
| 4.15 |
Consider the structures of some representative bicyclic and polycyclic
alkanes. |
| 4.16 |
Note the biological role of some relatively simple hydrocarbons. |
| 4.17 |
Recognize the relatively inert character of alkanes, aside from combustion. |
| 4.18 |
Learn the reagents, reaction conditions, types of starting materials
required and products formed for the reactions presented for the synthesis
of alkanes in sections 4.15A-C:
i) hydrogenation of alkenes and alkynes, ii) reduction of alkyl halides,
and iii) alkylation of terminal alkynes. Be able to write examples of each
reaction using R groups for generalized reactants and products. Be able
to translate an understanding of the general reactions to use of the reaction
conditions with specific molecules to form the corresponding products. |
| 4.19 |
Consider the benefits to our existence of carrying out organic syntheses
of useful molecules. Note the two types of transformations at the
heart of any organic synthesis. |
| 4.20 |
Begin to understand the notion and use of retrosynthetic analysis.
Be able to envision specific and logical retrosynthetic disconnections
and precursor intermediates when planning the synthesis of a given molecule.
Be able to evaluate the merits of various synthetic routes to a given molecule. |
Key Terms and
Concepts |
Use the Key Terms and Concepts list as a self-test for understanding
of these items. |
Assigned Problems: 1, 3b, 4a, 5ac, 7b,d,e, 8a,c,f,h, 9, 10(w/ models),
12, 13, 14, 15, 16, 17, 18, 19a-k, 20a,b,c,d,f, 23, 29, 34, 35, 39, 41,
48
| Section |
Goals |
| 5.1 |
Know the definitions of constitutional isomers, stereoisomers, enantiomers,
and diastereomers, and their relationship to each other. Be able to classify
the specific type of isomeric relationship between any one compound and
another. |
| 5.2 |
Be able to identify tetrahedral and trigonal stereocenters in molecules.
Be able to identify a compound as being chiral or achiral by testing for
superposability on its mirror image. Work on visualizing molecules in three-dimensions,
especially regions involving stereocenters. Do this by making models and
drawing dash-wedge structures of models, and by making models of drawn
structures. Understand the importance of mirror planes for determining
whether an enantiomer to a given molecule can exist. Understand the effect
of interchanging the position of any two groups at a tetrahedral stereocenter. |
| 5.3 |
Note the profound importance of chirality in natural products and biologically
active molecules. |
| 5.4 |
Read for interest. |
| 5.5 |
Be able to use the mirror plane test for chirality. |
| 5.6 |
In general, be able to assign the R or S configuration
to any tetrahedral stereocenter by correctly determing the relative priorities
of groups bonded to the stereocenter and determining the direction of priority
rotation. Specifically, be able to apply the priority rules to any type
of attached group, including those with multiple bonds. Develop expert
facility at visualizing the direction of rotation of the attached groups
at a tetrahedral stereocenter, according to their priorities and with a
mind's eye view from inside the "inverted umbrella" of the tetrahedron. |
| 5.7 |
Understand the definition of optical activity as the rotation of plane
polarized light by chiral molecules. Know that optical activity is measured
using instruments called polarimeters. Recognize that no obvious correlation
exists between the sign of rotation (+ or -) for an optically active molecule
and the R or S configuration of enantiomers. Understand that
an optical rotation measurement can be standardized for use as a physical
constant for a given optically active substance by calculating what is
known as the specific rotation, through taking into account sample characteristics
such as concentration, etc. |
| 5.8 |
Understanding the meaning of the term racemic mixture (or racemic form,
or racemate). Have an intuitive understanding of the origin of optically
activity and why there is no optical activity in a racemic mixture. |
| 5.9 |
Understand that a racemic mixture results when a chiral molecule is
formed by a chemical reaction between achiral starting materials and achiral
reagents. Consider how an optically active product might result from using
either chiral starting materials or chiral reagents. |
| 5.10 |
Not the importance of chirality in drug design and manufacture. |
| 5.11 |
Understand the ramifications of having more than one stereocenter in
a molecule ("n" stereocenters) with regard to the total number of isomers
possible (2n), how many enantiomer pairs are possible (2n-
1) and how many diastereomers could exist (2n-1). Understand
the relationship between diastereomers with regard to physical constants.
Be able to identify meso compounds. Be able to use the R-S
system to name compounds with more than one stereocenter. |
| 5.12 |
Understand how to draw and interpret Fischer projection formulas, while
recognizing the advantages and pitfalls of their use. |
| 5.13 |
Understand how stereoisomerism applies to cyclic molecules and be able
to recognize cases where planes of symmetry may influence the existence
or number of stereoisomers in cyclic compounds. |
| 5.14 |
Understand how the R or S configuration of a stereocenter
may or not be affected by the breaking and forming of bonds to the stereocenter
(according to the priorities of the new and old groups), and also how the
R
or S configuration of a stereocenter may or not be affected by the
breaking of bonds not directly attached to the stereocenter (according
to how a group's priority might change through remote alteration). Understand
the process of relating configurations between molecules by use of reactions
with known stereochemical outcome. |
| 5.15 |
Understand the principle behind methods for the separation of enantiomers,
i.e.
that reversible conversion of a pair of enantiomers into diastereomeric
species results in materials of differing physical properties, which after
separation could be used to regenerate each original enantiomer in isolated
form. |
| 5.16 |
Consider the possibility for chirality in allenes. |
Assigned Problems: 2, 3, 4, 5, 8, 9, 10, 11, 12, 13, 14, 16, 17, 19, 20ade,
21, 22 (for 20ad), 23, 26, 27, 30abcd, 33, 35a-j,nop, 38, 39, 40, 44
| Section |
Goals |
| 6.1 |
Know the general structural characteristics of an alkyl halide, re:
bond polarity, geometry, etc. Be able to readily identify an alkyl halide
as 1o (primary), 2o (secondary), or 3o
(tertiary). Be able to recognize vinylic and aryl halides (significant
because vinylic and aryl halides do not react by the mechanisms in Chapter
6). |
| 6.2 |
Note the names for some common organic halides, the solubility characteristics
of alkyl halides, and trends in boiling point and density according to
type of alkyl group or type of halogen (for a given alkyl group). |
| 6.3 |
Be able to write the general reaction for a nucleophilic substitution
reaction and identify the nucleophile, substrate (e.g. alkyl halide),
and leaving group. |
| 6.4 |
Gain thorough understanding of what a nucleophile is and be able to
recognize the nucleophilic participant in a reaction. Be able to recall
specific examples of nucleophiles. Understand the general character of
nucleophiles, such that you could identify potentially nucleophilic species
in a reaction. For specific examples where the nucleophilic atom bears
a hydrogen (e.g. HOH, ROH), understand the reason for a proton transfer
step after the substitution). |
| 6.5 |
Understand the general nature of a leaving group as being the species
that departs with a pair of electrons during a nucleophilic substitution
reaction. Learn to recognize the leaving group in substrates for nucleophilic
substitution. Recognize that the better a leaving group can accommodate
(stabilize) the electron pair it takes with it, the better will be the
leaving group. |
| 6.6 |
Know the meaning of SN2 in terms of reaction order
and the effect of the concentration of reactants on rate. Understand that
in SN2 reactions both the nucleophile and alkyl halide substrate
are involved in the rate determining step. |
| 6.7 |
As one of the most important sections in your study of organic chemistry,
commit to memory the general aspects of the SN2 reaction depicted
on page 236. Pay special attention to the site of nucleophic attack (backside
with respect to the leaving group), the structure of the transition state
(involving concerted bond forming to the nucleophile and bond breaking
to the leaving group), and the configuration of the product as compared
to the substrate (inversion of the tetrahedral center). |
| 6.8 |
Be able to draw a generic free energy diagram for an SN2
reaction, labeling the transition state, and showing the overall free energy
change for the reaction (deltaGo), whether it be endergonic
or exergonic. Understand the influence of the magnitude of the energy of
activation (deltaGo) on the rate of reaction. Understand the
influence of temperature on reaction rates. |
| 6.9 |
Further cement in place an understanding of SN2 reaction
as occuring by backside attack of the nucleophile with inversion of configuration
and simultaneous bond forming and breaking. Understand the ramifications
of inversion in SN2 reactions that take place at stereocenters.
Be
able to draw from memory and in three-dimensions a generic mechanism for
an SN2 reaction, including the transition state. |
| 6.10 |
Know that SN1 reactions are unimolecular in the rate determining
step. |
| 6.11 |
Ingrain the sequence of steps involved in any general SN1
reaction (see p. 245 for a specific example): 1) departure of the leaving
group (with the pair of electrons that bonded the LG to the substrate),
2) concomitant formation of a carbocation at the carbon that lost the LG,
and 3) attack of the nucleophile on the carbocation. Understand that there
may be proton transfer steps necessary, depending on the nature of the
nucleophile and leaving group, but consider the above three stages the
essential components of every SN1 reaction. |
| 6.12 |
Cement an understanding of the orbital and 3D structure of a carbocation,
especially the planar nature of the sp2 carbon and the
vacant p orbital. Know the general trend in relative carbocation
stability. |
| 6.13A |
Understand how the stereochemical outcome of an SN1 reaction
at a stereocenter (i.e. racemization) follows from the planar structure
of the intermediate carbocation (allowing both frontside and backside attack
by the nucleophile). Be able to draw from memory and in three-dimensions
where appropriate the stepwise mechanism for a generic SN1 reaction,
as outlined in the three steps of section 6.11. |
| 6.13B |
Recognize solvents as potential nucleophiles in SN1 reactions
and understand the concomitant proton transfer steps that are required. |
| 6.14 |
Be able to list and discuss the four most important factors affecting
rates of SN1 and SN2 reactions. |
| 6.14A |
Know how structure affects the rate of SN1 and SN2
reactions, i.e. steric hindrance for SN2 and relative carbocation
stability for SN1. |
| 6.14B |
Be able to assess the relative strength of a nucleophile, based on
it's charge or lack thereof, and relative basicity. Understand the effect
of concentration on the rate of SN2 reactions. |
| 6.14C |
Understand why polar aprotic solvents facilitate SN2 reactions.
Understand the structural difference between polar and aprotic solvents
and be able togive examples of each. |
| 6.14D |
Understand the ionizing ability of polar protic solvents and their
tendency to increase the rate of SN1 reactions. Recognize that
while water is a good ionizing solvent, many organic compounds are not
soluble in water, hence organic solvents such as methanol and alcohol are
frequently mixed with water to assist in solvation of the organic reactants. |
| 6.14E |
Learn some of the common leaving groups and recognize the common ability
among them to stabilize/accomodate the pair of electrons taken with them
when they act as leaving groups. Understand the inverse relationship of
base strength to leaving group ability. |
| 6.15 |
Be able to prepare compounds with a variety of functional groups by
transformation or incorporation of functional groups using SN2 reactions
on suitable substrates. Recall the unreactivity of vinyl and aryl halides
in SN1 and SN2 reactions. |
| 6.16 |
Be able to draw from memory a generic example of a dehydrohalogenation
reaction. Be able to recognize hydrogens (beta-hydrogens) eligible for
removal by a base, and the position of the double bond that will form upon
departure of the leaving group (from the alpha-carbon). |
| 6.16B |
Know the common bases used for dehydrohalogenation (also called 1,2-elimination). |
| 6.17 |
Ingrain in memory the general mechanism of an E2 reaction (in three-dimensions),
including the transition state, as depicted on page 267). |
| 6.18 |
Understand the mechanism of an E1 reaction, recognizing the possibility
for elimination of any beta- hydrogen from a carbocation intermediate,
in addition to the possiblity for an SN1 substitution. |
| 6.19 |
Understand the combined influence of factors such as base/nucleophile
strength and substrate structure (steric hindrance) with regard to competition
between SN2 and E2 reactions. With regard to SN1
and E1 reactions, recognize the inherent difficulty in directing a tertiary
substrate exclusively toward substitution. If substitution is desired,
attempt to use a 2o or 1o substrate. If elimination
is desired, use a strong base. |
| 6.20 |
Be able to prepare for yourself from memory a comparison of all
factors influencing whether each substrate type will undergo an SN1,
SN2, E1, or E2 reaction. |
Assigned Problems: 1, 2, 3, 4, 5, 7, 8, 9, 12, 13, 14, 15, 16, 17, 18,
19, 20, 21, 22, 23, 26, 29, 32, 33, 35
| Section |
Goals |
| 7.1 |
Note that olefin is an old term sometimes used to refer to an
alkene. |
| 7.2 |
Be able to apply the (E) and (Z) system for designating
alkene diastereomers (as a prefered alternative to cis and trans designations). |
| 7.3 |
Know the relative order of alkene stabilities (Section 7.3C)
and understand the thermodynamic evidence for this order (Sections 7.3A,
7.3B). |
| 7.4 |
Understand the relative stability of cycloalkenes as a function of
ring size. |
| 7.5 |
Gain acquaintance with the three elimination reactions presented here
for synthesis of alkenes. |
| 7.6 |
Review the essential E2 mech. Understand that if alkene synthesis is
desired, conditions favoring an E2 mechanism should be chosen. Be able
to describe reaction conditions favoring an E2 mechanism. |
| 7.6A |
Understand how a given elimination reaction might proceed to give more
than one product. Be able to identify all hydrogens eligible for removal
in an elimination reaction. Be able to predict the Zaitsev (more stable
alkene) product from a given reaction. |
| 7.6B |
Know conditions that could be used to favor elimination to form a less
substituted alkene. |
| 7.6C |
Be able to draw from memory the antiperiplanar transition state for
an E2 reaction. Be able to analyze and predict the products from elimination
reactions involving cyclohexane substrates. |
| 7.7 |
Know conditions for preparation of alkenes by dehydration of alcohols.
Understand the effect on ease of dehydration with respect to alcohol structure,
and the potential for carbocation rearrangements (see section 7.8). |
| 7.7A |
Be able to draw from memory a stepwise mechanism for acid-catalyzed
alcohol dehydration. Recognize this reaction as an E1 process for tertiary
and secondary alcohols. |
| 7.7B |
Recall the trend of carbocation stability and understand its influence
on ease of alcohol dehydration. |
| 7.7C |
Recognize that alcohol dehydration of a primary alcohol is essentially
an E2 process, or that it may involve hydride or alkanide migration with
concommitant formation of a more stable carbocation. |
| 7.8 |
Be able to recognize the potential for and predict molecular rearrangements
in a given substrate as a function of carbocation stability. Be able to
draw correct detailed curly arrow mechanisms for both hydride and alkanide
(alkyl) migrations, showing the initial carbocation and the carbocation
resulting after rearrangement. |
| 7.9 |
Be able to use debromination of a vicinal dibromide for synthesis of
an alkene. |
| 7.10 |
Know reaction conditions and substrate types suitable for synthesis
of alkynes. |
| 7.11 |
Recognize the acidity of terminal alkynes and know conditions (use
of the appropriate base) for forming an alkynide anion. |
| 7.12 |
Be able to utilize alkynide anions (starting with the corresponding
alkyne) for SN2 reactions to from new carbon-carbon bonds. Recognize
the limitation of only being able to use 1o alkyl halide substrates (otherwise
E2 occurs). |
| 7.13 |
Review the conditions and characteristics of the catalytic hydrogenation
of alkenes. |
| 7.14 |
Understand the function of the metal catalyst in catalytic hydrogenation
and the necessary stereochemistry resulting from hydrogen addition (syn)
by catalytic hydrogenation. |
| 7.15 |
Know reagents and reaction conditions for i) the exhaustive hydrogenation
of an alkyne (to form an alkane by addition of two molar equivalents of
hydrogen), ii) partial hydrogenation of an alkyne (to form an alkene by
one molar equivalent of hydrogen), and iii) conditions that will lead,
as desired, to specifically syn or anti addition of hydrogen to produce
Z or E alkenes, respectively. |
| 7.16 |
Be able to utilize the Index of Hydrogen Deficiency as a clue to structure
based on the molecular formula. Include consideration of the "Optional
Material" section. |
Assigned Problems: 1, 3, 5, 6, 7, 8, 9, 10, 11, 13, 14, 15, 17, 19acegik,
20, 21, 22abcdf, 23ac, 24, 26, 30, 38abd, 43, 44, 45, 46, 48
| Section |
Goals |
| 8.1 |
Recall the 3-D orbital structure of alkenes and the pi bond. Understand
how a pi bond can be a source of electron density for reaction with electrophiles.
Have a general understanding of electrophiles as Lewis acids and know relevant
examples. Be able to draw a generalized alkene addition reaction using
a generic E-Nu reagent. |
| 8.2 |
Be able to write a general reaction for the addition of a hydrogen
halide to an alkene. Recognize that addition of hydrogen halides to alkenes
constitutes a method for synthesis of alkyl halides. Understand the theoretical
basis for the most general statement of Markovnikov's rule. Be able to
apply it to the addition of any E-Nu reagent to an alkene. Understand the
meaning of the term regioselective. Note that carbocation rearrangements
are possible. Note that for HBr an exception to Markovnikov addition is
possible (Section 8.2D). That is, know the consequences with respect to
regiochemistry of using peroxides during addition of HBr to an alkene (anti-Markovnikov
addition). Be aware that the mechanism involves radicals (species wth unpaired
electrons) instead of ionic intermediates like we have seen thus far, and
that we will study mechanisms involving radicals in Chapter 10. |
| 8.3 |
Know the stereochemical outcome of addition to alkenes when a carbocation
is involved and understand the theoretical basis (the nature of the carbocation
intermediate). Also recognize the possibility for carbocation rearrangements
(see section 7.8). |
| 8.4 |
Understand the addition of cold sulfuric acid to alkenes within the
context of the general mechanism for addition of E-Nu reagents to alkenes. |
| 8.5 |
Know the acid-catalyzed hydration of alkenes and be able to draw a
detailed mechanism for this reaction. Note the regiochemistry of acid-catalyzed
hydration. Understand hydration of alkenes within the context of equilibrium
reactions and its converse reaction (dehydration of alcohols). Recognize
alkene hydration as a method for the synthesis of alcohols. |
| 8.6 |
Be able to write a three-dimensional mechanism for halogen (Br2,
Cl2) addition to an alkene. |
| 8.7 |
Understand the stereochemical consequences in the mechanism for halogen
addition to E and Z alkenes. Be able to determine the stereochemical
form of the products based on the structure of the starting alkene. Understand
what is meant when a reaction is said to be stereospecific. |
| 8.8 |
Know how halohydrins are prepared and understand the mechanism for
their synthesis as a variation on the theme of halogen addition to alkenes
with participation of a nucleophilic solvent. |
| 8.9 |
Know some methods for making carbenes and how to use them to prepare
cyclopropane compounds from alkenes. |
| 8.10 |
Know how to prepare 1,2-diols from alkenes using OsO4. Recognize
the stereospecific aspect of this reaction (syn hydroxylation). Cold KMnO4
can also be used for syn hydroxylation. |
| 8.11 |
Know the oxidative cleavage reactions of alkenes using either hot KMnO4
or ozone (O3), including conditions and the specific form of
products obtained (aldehydes. ketones, carboxylic acids). Be able to think
retrosynthetically with regard to what reaction conditions could be used
to prepare a given compound. |
| 8.12 |
Know the addition reactions of halogens to alkynes, noting that reaction
with either one or two molar equivalents of reagent is possible with an
alkyne (as compared with an alkene). |
| 8.13 |
Note the regioselectivity of addition of one or two molar equivalents
of a hydrogen halide to an alkyne. |
| 8.14 |
Note that carboxylic acids can be prepared by oxidative cleavage of
alkynes. |
| 8.15 |
Place all of the reactions in this chapter (and from previous chapters)
within the context of being able to use them to synthesize molecules by
a series of reactions. Practice retrosynthetic analysis by looking for
functional groups and carbon-carbon bond disconnections that you now know
how to prepare by various reactions. That is, consider how reactions can
be used to form carbon-carbon bonds, interconvert functional groups, and
control stereochemistry and/or stereochemistry. Note how the stereochemistry
and regiochemistry of each reaction must be considered in the planning
of any synthesis. |
| Summaries |
Use the scheme on page 358 as a review and summary of alkene addition
reaction conditions, regiochemistry, and stereochemistry. Organize your
knowledge of addition reactions of alkenes according to 1) which functional
groups can be prepared by each reaction, and 2) the stereochemical and/or
regiochemical outcome of each. Begin to consider how various addition reactions
could be applied to synthesis of compounds with the type of functional
groups resulting from addition to alkenes. Also note how cleavage reactions
can be used for synthesis of various functional groups. Use the scheme
on page 359 to place in perspective the addition reactions of alkynes by
comparing and contrasting the various outcomes with respect to product
functional group and reaction stereochemistry and/or regiochemistry. |
Assigned Problems: 2, 3, 5, 6, 7, 8, 9, 11, 15, 16, 17, 19, 20, 21abfghijklmn,
22giklmn, 23, 27, 28, 31, 34, 36, 38, 42, 50, 51
| Section |
Goals |
| 9.1 |
Know the definition of spectroscopy. |
| 9.2 |
Understand the general properties of waves (wavelength, frequency,
units used in describing waves). Gain a general appreciation for wavelength
and the relative energy of various regions of the electromagnetic spectrum. |
| 9.3A,B |
Read for background and general understanding of the basis for nuclear
magnetic resonance (NMR). |
| 9.3C |
Understand the meaning of "chemical shift", the reason for differences
in chemical shift from one nuclear environment to another, and the use
of the terms "upfield" and "downfield". Understand interpretation of chemical
shift with respect to number of peaks in an NMR spectrum and the number
of different types of hydrogens in a molecule. |
| 9.3D |
Understand the interpretation of integral curves, i.e. the correspondence
of peak area with the number of hydrogens producing a given signal. |
| 9.3E |
Know what is meant by "signal splitting" (the interpretation of which
will be explained in later sections). |
| 9.4 |
Read for general understanding. |
| 9.5 |
Recognize that nuclei can be shielded or deshielded from the applied
magnetic field in an NMR spectrometer by the influence of electron density
and circulating electrons near a given nucleus. As a result, the position
of peaks for nuclei in various environments fall in predictable chemical
shift regions. (see Table 9.1) |
| 9.6 |
Be able to use Table 9.1 for predicting the chemical shifts of hydrogens
in molecules. Know that TMS is the reference standard (with a chemical
shift of zero) for the chemical shift scale. |
| 9.7 |
Be able to identify chemically equivalent (and therefore chemical shift
equivalent, or homotopic) nuclei in NMR spectra. Know what enantiopic and
diastereotopic hydrogens are. |
| 9.8 |
Using the n+1 rule for signal splitting, be able to predict the number
of peaks in an NMR spectrum for a given set of hydrogens, bearing in mind
the relevance of chemically equivalent (homotopic), enantiotopic, and diastereotopic
hydrogens. Be able to work backwards from spin-spin splitting patterns
in a spectrum to determine how many hydrogens are neighboring the hydrogens
giving rise to the signal being interpreted. Understand the reciprocity
of coupling constants. |
| 9.9 |
Know that rapid conformational change leads to a signal that is a weighted
average of the environments experienced by a given nucleus. Know
that spin-spin splitting is usually not observed between hydrogens on O
and N atoms (e.g. alcohols, amines, and carboxylic acids) and the hydrogens
on carbon atoms adjacent to these groups, due to chemical exchange by virtue
of their acidity. |
| 9.10 |
Be able to interpret 13C NMR spectra (elucidate a structure)
using chemical shift and DEPT information (with chemical shift table 9.2).
Be able to predict a 13C NMR spectrum for a compound with a
given structure. |
| 9.11 |
Know how to interpret COSY and HETCOR two-dimensional NMR spectra. |
| 9.12 |
Understand the meaning of the axes in a mass spectrum and be able to
recognize the appearance of mass spectral data, as compared to IR and NMR
data. |
| 9.13 |
Be able to write a general equation for electron impact ionization
and understand the process in a general sense. Know that fragmentation
can occur. Understand the general principles of how a mass spectrometer
sorts ions of different masses. |
| 9.14 |
Understand what the molecular ion (M+) and base peak are in a mass
spectrum. Understand that M+1 peaks (and M+2 peaks) are caused by
the presence of isotopic nuclei in molecules. |
| 9.15 |
Know how to use the M+1 peak in a mass spectrum to calculate the molecular
formula for a compound. |
| 9.16 |
Be able to draw fragmentation equations (showing single electron movements
with single-barbed arrows). Know that electron impact ionization
occurs most easily by dislodging a nonbonding and pi electron, and that
fragmentation usually occurs at adjacent bonds. Know that fragmentation
is especially likely when cleavage forms a relatively stable carbocation
(e.g. an allylic cation or acylium ion). Know that cleavage can also
involve if a hydrogen atom can be transfered and/or if a cyclic transition
state can occur (e.g. the McLafferty rearrangement). |
| 9.17 |
Know the meaning of the acronym GC/MS and that it is a very powerful
and widely used technique for separation and identification of compounds. |
| 9.18 |
Know that mass spectrometry can be done with nonvolatile and very large
molecules (e.g. polymers and biomolecules) using "soft" ionization techniques. |
Assigned Problems: 1, 2, 3, 4, 5, 6, 8, 11, 13, 14, 15, 20, 21, 23, 24,
25, 26, 28, 29, 32, 33, 35, 39
| Section |
Goals |
| 10.1 |
Understand the difference between heterolytic and homolytic bond cleavage
with regard to respective formation of ionic and free radical reaction
intermediates. Be able to use single-barbed arrows to clearly and accurately
show single electron movements in reactions of radicals. Know the common
ways of producing radicals. Recognize the importance of radicals in industry
and biological processes. |
| 10.2 |
Be able to calculate the overall enthalpy change (Delta H, or heat
of reaction) for bond forming and/or bond breaking steps, given the bond
dissociation energies (DHo) for each pertinent species. Know
whether to apply a positive or negative mathematical sign to each bond
dissociation energy used in an enthalpy calculation. Know the relative
order of alkyl radical stability (3o > 2o > 1o). |
| 10.3 |
Recognize the possibility for both multiple halogen substitution and
the formation of constitutional isomers in free radical halogenation of
alkanes. Note that use of an excess of alkane with respect to the halogen
can lead to primarily mono-substitution (although without selectivity for
chlorination). Recognize the importance of symmetry in determining the
number of possible products. Know the relative reactivites of chlorine
and bromine, i.e. that chlorine is more reactive but less selective whereas
bromine is less reactive but more selective. |
| 10.4 |
Know, as a simple example to be extended to other compounds later,
the chain reaction mechanism for free radical halogenation of methane,
including the chain initiating, chain propagating, and possible chain terminating
steps. Understand that the sum of the chain propagating steps is equivalent
to the overall reaction equation. |
| 10.5 |
Know how to calculate the overall Delta H for a reaction by summing
the Delta H for the chain propagation steps. Read for general understanding
the explanations involving transition state theory. Note that 1)
radical chlorination and bromination are energetically feasible, 2) radical
fluorination is very exergonic (so much so as to be impractical outside
of industrial laboratories), and 3) radical iodination is energetically
unfavorable and therefore not feasible. |
| 10.6 |
Recognize that chlorination is relatively non-selective regarding the
position of substitution, and therefore typically leads to a mixture of
products. Consider free radical bromination as a synthetically useful
reaction due to its relative selectivity as compared to chlorination. |
| 10.7, 10.8 |
Know the hybridization of a carbon radical and be able to draw a three-dimensional
dash-wedge structure for a carbon radical intermediate. Understand the
ramifications of this structure with regard to radical reactions that involve
or produce a stereocenter. Be able to predict whether a free radical reaction
will lead to stereoisomers, and if so, whether enantiomers or diastereomers
would be formed. |
| 10.9 |
Understand the mechanistic basis for anti-Markovnikov addition of HBr
to alkenes in the presence of peroxides. Recognize the utility of
this method as a regiochemical complement to HBr addition to alkenes in
the absence of peroxides (Markovnikov addition). |
| 10.10 |
Know the general mechanism for free radical chain-growth polymerization
of alkenes. Consider the specific examples of polyethylene, polystyrene,
and others listed. See the Special Topic on chain-growth polymers
for further information. |
| 10.11 |
Recognize the relevance of radical chain reactions in combustion, autoxidation
(air oxidation), and reactions of halogen radicals with ozone. Consider
the example of hydroperoxide formation shown by autoxidation of a polyunsaturated
fat. |
Assigned Problems 1c,d,f, 2, 4, 7, 11, 13, 14, 16, 17, 18, 19, 20, 22,
,23, 25, 28
Although there are many new reagents and reactions in this chapter,
there is little new regarding general mechanisms and reaction types. Attempt
to place each new reaction within the context of a general mechanistic
class you have already learned, i.e. addition reactions of alkenes (oxymercuration-demurcuration,
hydroboration-oxidation, epoxide synthesis), nucleophilic substitution
(tosylates, mesylates, alkyl halide and ether synthesis from alcohols,
and epoxide ring opening), and general acid-base principles.
| Section |
Goals |
| 11.1 |
Be able to name alcohols by the IUPAC system. Be able to name ethers
using common radicofunctional names for simple ethers or IUPAC substitutive
names for more complicated ethers. Be able to distinguish a phenol from
an alcohol, and recognize benzyl and allyl alcohols/ethers. Be able to
write the general formula (using R groups) for an alcohol or ether. |
| 11.2 |
Understand the general differences in terms of intermolecular forces
between alcohols and ethers. |
| 11.3 |
Read for general information and appreciation of practical applications
for some alcohols and ethers. |
| 11.4 |
Recall and review alcohol synthesis by hydration of alkenes. Recall
the limitations of this method (carbocation rearrangements, etc.). |
| 11.5 |
Be able to synthesize an alcohol using the oxymercuration-demurcuration
protocol. Know its benefits (lack of molecular rearrangements) and regiochemistry
(Markovnikov). Recognize the potential for ether synthesis by making
the solvent nucleophile an alcohol instead of water (solvomercuration-demurcuration). |
| 11.6, 11.7 |
Know the reaction conditions for the hydroboration-oxidation synthesis
of alcohols [1) BH3:THF, 2) H2O2, OH-].
Know the stereochemistry for the overall addition of the hydrogen and hydroxyl
group (syn) and the regiochemistry (anti-Markovnikov). Recognize hydroboration-oxidation
as a synthetic compliment to oxymercuration-demurcuration with respect
to regiochemistry. |
| 11.8 |
Recall the essential properties of alcohols: the alcohol oxygen is
moderately nucleophilic and weakly basic, the alcohol hydroxyl group is
a poor leaving group unless first protonated or converted into a leaving
group by formation of some type of sulfonate ester (e.g. a tosylate, mesylate,
triflate). |
| 11.9 |
Recall that alcohols are weakly acidic and can form strong alkoxide
bases/nucleophiles upon deprotonation by a stronger base (e.g. NaH) or
an alkaline earth metal (Na or K). |
| 11.10 |
Know the reaction conditions for forming tosylates and mesylates and
the structures of the products, including those written with the Ts or
Ms abbreviation. Disregard the mechanism of formation unless interested. |
| 11.11 |
Know that alkyl sulfonates can be used as an indirect method for accomplishing
SN2 nucleophilic substition of the hydroxyl group in an alcohol
(initial conversion of the alcohol to an alkyl sulfonate leaving group
followed by SN2 substitution by the desired nucleophile). |
| 11.12 |
This is a preliminary introduction to sections 11.13 and 11.14. |
| 11.13 |
Recognize that alcohols can be converted to alkyl halides by reaction
with the appropriate HX. Understand the mechanism as simply application
of acid-base reactions followed by nucleophilic substitution. |
| 11.14 |
Know PBr3 and SOCl2 as the preferred reagents
for conversion of 1o and 2o alcohols to alkyl bromides
and chlorides, respectively. |
| 11.15 |
Recognize the intermolecular dehydration of alcohols as a method for
synthesis of symmetrical ethers. Understand the mechanism as simply applications
of acid-base and nucleophilic substitution reaction mechanisms. Know how
to accomplish a Williamson ether synthesis (11.15B) and recognize it's
limitations according to the requirement that it be an SN2 reaction.
Note the use of tert-butyl ethers and silyl ethers as protecting
groups. |
| 11.16 |
Understand the reactions of ethers with acids as protonation to form
a leaving group followed by nucleophilic substitution to form the respective
products. |
| 11.17 |
Know the general structure of an epoxide and the reagents used for
their formation from alkenes (peroxy carboxylic acids, i.e. RCOOOH or RCO3H).
Know the stereochemistry of oxygen addition (syn, by default, with retention
of the original alkene geometry). |
| 11.18 |
Understand the principles of acidic or basic ring-opening of epoxides,
and know the mechanistic/regiochemical implications of each (e.g. regiochemistry
of attack by the nucleophile). |
| 11.19 |
Recognize epoxidation followed by hydrolysis (acidic or basic) as a
means for anti-hydroxylation of alkenes. |
| 11.20 |
Note the use of crown ethers as phase transfer reagents and the biochemical
significance of ionophore antibiotics (11.20B). |
| 11.21 |
Use this section to tie together the various reactions and their stereochemical
and regiochemical ramifications. Consider how each reaction could be used
in synthesis problems. Categorize reactions according to the types of functional
groups each one allows you to form, the functional groups required in the
starting materials, and the stereochemical/regiochemical control each reaction
may exhibit. |
Assigned Problems: 2, 3, 4, 5, 6b 7, 10ace, 12, 15, 16, 17, 18, 19, 20,
22, 23, 24, 25, 26, 28, 31, 32acdegh, 33, 34, 35acd, 36, 38, 39, 40, 42,
43, 44, 45ad, 46, 47, 48
This chapter is largely devoted to methods for the interconversion of
functional groups by oxidation and reduction and the formation of carbon-carbon
bonds by reactions of organometallic reagents. Work toward expanding your
synthetic repertoire and developing your retrosynthetic analysis skills.
| Section |
Goals |
| 12.1 |
Know the structure of the carbonyl group with respect to hybridization,
bond angles, and C==O polarity. Note the general reaction for nucleophilic
addition to carbonyl groups. Especially relevant to this chapter is the
nucleophilic addition of hydride and organometallic carbanion-like reagents. |
| 12.2 |
Know the general definitions of oxidation and reduction as applied
to organic compounds (with regard to hydrogen and oxygen content). Know
the relative order of oxidation state when comparing alcohols, aldehydes
and ketones, carboxylic acids, and esters. |
| 12.3 |
Be able to draw the structure of each respective product resulting
from lithium aluminum hydride (LiAlH4, or LAH) reduction of
any aldehyde, ketone, carboxylic acid or ester. Recognize the lesser reducing
power of sodium borohydride (NaBH4) as compared to LiAlH4.
Know the functional groups that can be reduced by NaBH4 and
be able to draw structures for the resulting products. Note the common
characteristic in these reactions of hydrogen with an electron pair (i.e.
hydride) attacking a carbonyl carbon. |
| 12.4 |
Know how to prepare an aldehyde from a 1o alcohol using
PCC (pyridinium chlorochromate). Know how to prepare a carboxylic acid
from a 1o alcohol using basic KMnO4 followed by acidification.
Know how to prepare a ketone from a 2o alcohol using H2CrO4
(chromic acid). Recognize that 3o alcohols cannot be oxidized. |
| 12.5 |
Understand the general polarity of carbon-metal bonds and the potential
for the carbon in an organometallic compound to be strongly nucleophilic
or basic. |
| 12.6 |
Know how to prepare organolithium (RLi) compounds organomagnesium
compounds (RMgX, Grignard reagents). |
| 12.7 |
Know the products that result when organolithium and organomagnesium
compounds react with a) compounds containing acidic (even relatively weakly
acidic) hydrogens, b) epoxides, and c) carbonyl compounds. Understand these
reactions as being due to either the strongly basic or powerfully nucleophilic
nature of the RLi and RMgX reagents. Note that neither RLi nor RMgX reagents
can be used for SN1 and SN2 nucleophilic substitution
reactions because they would primarily cause E2 elimination by their strongly
basic character. |
| 12.8 |
Know how to synthesize 1o, 2o, or 3o
alcohols from the appropriate aldehyde or ketone by a Grignard reaction.
Note, as an aside, the reaction of two molar equivalents of a Grignard
reagent with an ester. |
| 12.8A |
Study the retrosynthetic and synthetic methodologies that become possible
using Grignard reactions and other reactions in your repertoire. Practice
synthesis and retrosynthetic analysis on a variety of target molecules.
Become versatile with functional group interconversions and C-C bond forming
reactions. |
| 12.8B, C and D |
Understand that limitations exist for the use of Grignard and organolithium
reagents when other functional groups are present in a molecule that would
react competitively or instead of reaction in the desired way (11.8B).
Note the parallel reactivity of RLi and Grignard reagents (12.8C). Note
that sodium alkynides also undergo addition reactions to carbonyl groups
of aldehydes and ketones (12.8D). |
| 12.9 |
Know how to prepare lithium dialkylcuprate reagents from alkyl halides.
Know the scope and limitations for using lithium dialkylcuprates for carbon-carbon
bond forming reactions. |
| 12.10 |
Understand, in general, what a protecting groups is and how one might
be used in the course of a reaction involving an incompatible functional
group. tert-Butyl ethers and silyl ethers are previously mentioned
protecting groups for alcohols. |
Assigned Problems: 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,
19, 20, 21, 22, 24, 26, LGP 1 and 2
| Section |
Goals |
| 13.1 |
Understand the general structures possible for the following three
types of conjugated systems: allylic radicals, allylic cations, and conjugated
alkenes. |
| 13.2 |
Know the general reaction for allylic halogenation. Be able to write
the general reaction conditions for allylic chlorination (Sect. 13.2A).
Recall the steps of radical reaction mechanisms and apply them to radical
allylic substitution. Be able to write reactions for allylic bromination
using NBS (Sect. 13.2B). |
| 13.3 |
Understand the molecular orbital representation of the allylic radical
and the accompanying rationale for its relative stability. Be able to draw
resonance structures of an allylic radical. |
| 13.4 |
Understand the molecular orbital representation of the allylic cation
and the accompanying rationale for its relative stability. Be able to draw
resonance structures of an allylic cation. |
| 13.5 |
Refine your understanding of resonance structures (first introduced
in Section 1.8). Recognize that individual resonance forms of a molecule
do not exist, but that the true form of a molecule is a hybrid of the contributing
resonance structures. Be able to draw resonance structures that follow
the rules prescribed in this section. Be able to evaluate the relative
contribution of a given resonance form to that of the overall resonance
hybrid. |
| 13.6 |
Be able to provide complete IUPAC names for polyunsaturated hydrocarbons.
Be able to classify specific examples as being conjugated, cumulated, or
isolated polyunsaturated compounds. |
| 13.7 |
Become familiar with the structure of 1,3-butadiene with respect to
its two most likely conformations and its molecular orbital representation. |
| 13.8 |
Note that conjugated unsaturated systems are thermodynamically more
stable than corresponding isolated unsaturated systems. |
| 13.9 |
Know the mathematical relationship between absorbance, molar absorptivity,
concentration, and path length. Understand that spectroscopy of organic
molecules in the ultraviolet and visible (UV/Vis) wavelength regions is
typically due to energy transitions of nonbonding (n) and pi bonding electrons.
Recognize that the energy of these transitions decreases with increasing
conjugation in the molecule. Note that an understanding of molecular orbital
(MO) theory is very helpful in understanding UV/Vis spectroscopic absorptions.
Recognize that UV-Vis spectroscopy is an important analytical tool in biochemical
and environmental studies. |
| 13.10 |
Recognize the possibility of 1,2 and 1,4 electrophilic addition pathways
in conjugated dienes. Understand that the 1,2 and 1,4 addition products
result from a common intermediate, i.e. an allylic cation. Be able to write
a mechanism depicting formation of both 1,2 and 1,4 addition products.
Understand the terms kinetic control and thermodynamic or equilibrium control
(Sect. 13.10A). Be able to interpret, in terms of these effects, the 1,2
to 1,4 product ratio resulting from addition to a conjugated system at
high and low temperature. |
| 13.11 |
Know the general depiction of a Diels-Alder reaction and be able to
classify each reactant as either the diene or dienophile. Recognize the
stereospecific aspects of the Diels-Alder reaction, in terms of syn addition,
diene reaction from the s-cis conformation, and the preference for endo
products. Be able to incorporate these stereochemical attributes when writing
the structure of Diels-Alder adducts. Be able to utilize the stereospecificity
of the Diels-Alder reaction when planning an organic synthesis. |
Assigned Problems: 1,2,3,4,6,7,8,10,11,12,13,16,18,19, 20, 21, 23, 24,
34, 40
| Section |
Goals |
| 14.1 |
Note the history of discovery of aromatic compounds and the role of
benzene as the parent in this family. Note the modern meanings of the classifications
aliphatic and aromatic. |
| 14.2 |
Develop facility in naming aromatic compounds as derivatives of benzene
(e.g. methylbenzene) and for some, as aromatic compounds with common names
(e.g. toluene). Be able to correctly apply the prefixes ortho, meta, and
para when naming disubstituted benzenes, as well as numbers to designate
substituent positions in di- and higher substituted benzenes. Gain clear
understanding of the terms phenyl (and its abbreviations) and benzyl as
structural moieties. |
| 14.3 |
Recognize the unique stability of benzene enuder various reaction conditions
in which ordinary unsaturated compounds would react. Note, as an exception,
that benzene can undergo substitution reactions, although it is by a mechanism
to be covered in Chapter 15. |
| 14.4 |
Gain facility in representing benzene and related compounds using bond-line
structural formulas.Note the equivalency of the two possible resonance
forms that can be drawn for the ring in benzene and related compounds. |
| 14.5 |
Recognize the special stability of benzene as indicated by thermodynamic
comparison of actual hydrogenation to cyclohexane with hypothetical hydrogenation
of cyclohexatriene. |
| 14.6 |
Further secure an understanding of the bond-line representations of
benzene as being two equally contributing resonance forms, and that a hybrid
structure can be drawn using a circle within the hexagon instead of three
double bonds alternating with three double bonds. Equally important, gain
an appreciation for the molecular orbital representation for benzene as
having six sp2 hybridized carbons whose individual p
orbitals overlap to form continuous pi electron molecular orbitals above
and below the plane of the carbon ring (Sect. 14.6B). |
| 14.7 |
Be able to apply the Huckel 4n+2 rule to characterize as aromatic
or not any planar cyclic compound where each atom has a p orbital.
Recognize the applicability of this system for characterizing annulenes
(Sect 14.7A). |
| 14.7B |
Note that NMR spectroscopy confirms the identical nature of the hydrogen
atoms in benzene. Revisit the concepts of shielding and deshielding in
NMR spectroscopy (Section 9.5) and incorporate an understanding of the
aromatic nature of benzene to rationalize the downfield chemical shift
of the benzene hydrogens (specifically the effect called ring current).
Similarly, consider the effect of ring current on the chemical shift of
internal hydrogens in large-ring aromatic compounds. |
| 14.7C |
Recognize that some planar, cyclic ions can be classified as aromatic
by the Huckel rule. Be able to characterize cyclic ionic compound as being
aromatic or not. Note consistency of the molecular orbital representation
of aromatic ions with molecular orbital depictions of neutral aromatic
compounds. |
| 14.7D |
Note the definitions of antiaromaticity and nonaromaticity, as well
as examples of each. |
| 14.8A |
Recognize the existence of polycyclic benzenoid aromatic compounds.
Understand the rationale behind "peripheral" aromaticity observed in some
polycyclic aromatic compounds, e.g. pyrene. |
| 14.8B |
Recall the examples of nonbenzenoid aromatic compounds given thus far,
including aromatic ions, and use these to understand the polar nature of
azulene. |
| 14.8C |
Note the intriguing architecture of fullerene compounds and the phenomenal
potential for their practical use. |
| 14.9 |
Be able to determine whether a given heterocyclic compound is or is
not aromatic. |
| 14.10 |
Note the pervasive importance of aromatic compounds in biochemistry,
e.g. their roles in aromatic amino acid and nucleic acid structure. Also
note examples of toxic aromatic compounds. |
| 14.11 |
Be able to rationalize the proton and carbon NMR chemical shifts in
spectra of aromatic compounds on the basis of both aromaticity and the
effects of substituent on electron density distribution. Know the characteristic
IR frequency range for C-H stretching in aromatic compounds and note that
substitution patterns in substituted benzene compounds can be indicated
by certain low frequency IR absorptions by the ring. Note typical
characteristics of UV-Vis and mass spectra of aromatic compounds. |
Assigned Problems: 4b,c,d,5b,c,7,10,11,12,13,14,15,16,21,22,25,27,29,31,32,33,35
| Section |
Goals |
| 15.1 |
Know the general form of an electrophilic aromatic substitution reaction
and note the specific examples of reactions to be discussed later in detail. |
| 15.2 |
Be able to draw a detailed mechanism for an electrophilic aromatic
substitution using a generic electrophile. Note the relative rates of each
step. Be able to write the accompanying free-energy diagram for a typical
electrophilic aromatic substitution reaction. Be able to draw resonance
forms for the arenium ion. |
| 15.3 |
Be able to write the overall reaction for chlorination or bromination
of benzene using typical conditions. Be able to identify the electrophilic
species and draw a detailed mechanism. |
| 15.4 |
Be able to write the overall reaction for nitration of benzene using
typical conditions. Be able to identify the electrophilic species and draw
a detailed mechanism. |
| 15.5 |
Be able to write the overall reaction for sulfonation of benzene using
typical conditions. Be able to identify the electrophilic species and draw
a detailed mechanism. Note the reversibility of this reaction and the conditions
required for desulfonation. |
| 15.6 |
Know the general reaction for Friedel-Crafts alkylation and be able
to draw a detailed mechanism involving formation of a carbocation intermediate.
Recognize that by using appropriate conditions various types of starting
materials can be used to form alkyl carbocations which may then be involved
in Friedel-Crafts alkylation. Be able to write generic examples of some
of these reactions. |
| 15.7 |
Be able to write Friedel-Crafts acylation reactions starting with either
acyl halides or carboxylic acid anhydrides. Know how to prepare an acid
chloride from a carboxylic acid. Be able to write a detailed mechanism
for Friedel-Crafts acylation involving an acylium ion. |
| 15.8 |
Know the limitations of Friedel-Craft alkylations with respect to both
the specific aromatic and alkylating reactants. Be able to choose appropriate
reactants given a desired product. |
| 15.9 |
Note the synthetic advantages of achieving net Friedel-Crafts alkylation
through F-C acylation followed by Clemmensen reduction of the resulting
aryl ketone. Be able to write the reactions involved in a general sequence
of this type. |
| 15.10 |
Know how to characterize a benzene substituent as an activating or
deactivating group. Know the meaning of the designations ortho-para director
and meta director as applied to a benzene ring substituent. Recognize that
activating groups are ortho-para directors and that deactivating groups
are meta directors (except for halogen substituents which are ortho-para
directors but deactivating). In general,. be able to classify any substituent
group as activating or deactivating, and as an ortho-para or meta director. |
| 15.11A,B |
Regarding the relative stability of substituted arenium ions, be able
to explain the stabilizing effect of electron releasing substituents and
the destabilizing effect of electron withdrawing substituents by inductive
and/or resonance explanations. Be able to draw resonance structures for
all possible carbocation resonance contributors to a given substituted
arenium ion hybrid. Know the relative electron donating ability of the
following substituent types: amino, hydroxyl or alkoxyl, and halo substituents. |
| 15.11C |
Be able to explain the orientation of substitution (meta) on a benzene
ring with an electron withdrawing substituent using arguments of relative
electron density in the various potential arenium ion intermediates. |
| 15.11D,E |
Be able to explain the orientation of substitution (ortho and para)
on a benzene ring bearing either a resonance or inductive electron donating
substituent. Employ arguments incorporating resonance structures for various
potential arenium ion intermediates, both when the directing substituent
has and does not have one or more non-bonding electron pairs. Note the
special case of halogens as being ortho-para directors due to resonance
participation but deactivating substituents due to inductive electron withdrawing
effects. |
| 15.11F |
Be able to classify any substituted benzene as being activated or deactivated
toward electrophilic substitution, and according to whether the substituent
is a meta or ortho-para director. |
| 15.12 |
Be able to identify the benzylic position in alkylbenzene compounds
and to justify the stability of benzylic radicals and cations using resonance
structures. Recognize the use of benzylic halogenation as a synthetic route
for introduction of halogens in alkylbenzenes. Be able to write a radical
chain mechanism for benzylic halogenation. |
| 15.13A,B |
Note the enhanced stability of an alkene that is conjugated with an
aromatic ring, and the influence of an aromatic ring on the regiochemistry
of reactions that form alkenes (preference to form the double bond so that
it is conjugated with the aromatic ring). Conversely, note that addition
reactions to double bonds of alkenylbenzenes will involve the formation
of an intermediate carbocation or radical that is preferentially in the
benzylic position. |
| 15.13C,D |
Know the reaction condition for oxidizing alkyl, alkenyl, alkynyl,
and acyl benzene substituents to a carboxylic acid group (hot, basic KMnO4
followed by dilute acid). Note the synthetic use of this reaction for preparing
benzoic acid derivatives. Also note and be able to use alternative conditions
that allow selective oxidation of the benzene ring itself to a carboxylic
acid group, leaving the original side chain intact (O3 followed
by H2O2). |
| 15.14 |
Be able to orchestrate a sequence of aromatic ring reactions so that
the desired orientation of substituents is achieved in the final product.
Note that some directing groups (e.g. amino and hydroxyl) are such powerful
activators that they must be "protected" as lesser activating groups (by
acetylation) while conducting electrophilic aromatic substitution reactions.
Know how to add and remove these protecting groups. Also learn to use removable
directing groups such as the sulfonic acid group for temporary directing
effects. Be able to evaluate the orientation of substitution in a disubstituted
benzene reactant. |
| 15.15 |
Recall the factors that influence relative ease of SN1 and
SN2 reactions, including steric effects, and, for SN1
reactions only, stability of the intermediate carbocation. Place allylic
and benzylic halides in this scheme of relative reactivity (vs. ordinary
1o, 2o, and 3o halides) and be able to
rationalize their generally enhanced reactivity under conditions favoring
either SN1 or SN2 mechanisms. |
| 15.16 |
Note that aromatic compounds can be reduced completely to cyclohexanes
by hydrogenation with nickel catalysis, and some aromatic compounds can
be converted to cyclohexene derivatives by Birch reduction. Birch reduction
of aryl ethers can be used to prepare 2-cyclohexenones. |
Assigned Problems: 1,2,3,4,5,6,7,9 (w/o using Table 15.2),10,11,13,14,15,16,17,18,19,20,21,22,23,26a,b,d,e,f,27a,e,28,
29a,c,e,g,i,j,30a-g,i,k,n,31a,b,c,d,32a,b,33,34,35,36,38,39,40,42,43,45,50,54,55
| Section |
Goals |
| 16.1 |
Know the general formula for an aldehyde or ketone Be able to recognize
either functional group in any structural formula. |
| 16.2 |
Be able to name aldehydes and ketones using the IUPAC system. Gain
facility in applying the prefix names methanoyl (or formyl) and ethanoyl
(or acetyl) for compounds that bear these groups as substituents. |
| 16.3 |
Recognize the inherent polarity of the carbonyl group. Note the absence
of hydrogens available for hydrogen bonding in simple ketones and aldehydes
(unless other functional groups are present). |
| 16.4A |
Recall the synthesis of aldehydes by oxidation of primary (1o)
alcohols using PCC (pyridinium chlorochromate). |
| 16.4B |
Know which functional groups can be reduced to an aldehyde using lithium
tri-tert-butoxyaluminum hydride and diisobutylaluminum hydride (DIBAL-H).
Be able to use either reagent to synthesize an aldehyde by choosing an
appropriate reactant and reaction conditions. Know (at least) the common
aspects of the mechanisms for these reductions, i.e. transfer of a hydride
ion from the reducing agent to the electrophilic carbon atom of the reactant
(the carbonyl of an acyl halide or ester, or nitrile carbon). |
| 16.5A |
Recall methods for the synthesis of ketones by a) ozonolysis of appropriate
alkenes, b) Friedel-Crafts acylation of aromatic compounds, and c) oxidation
of secondary (2o) alcohols. |
| 16.5B |
Know how to prepare a ketone by hydration of an alkyne with mercury
catalysis. Note that Markovnikov's rule is followed for hydration of terminal
alkynes and that a mixture of ketones can occur from hydration of an internal
ketone. |
| 16.5C |
Note that an acyl halide can be used to synthesize a ketone by the
Corey-House, Posner-Whitesides lithium dialkylcuprate reaction. |
| 16.5D |
Note that reaction of nitriles with either Grignard or alkyl lithium
reagents leads to ketones upon hydrolytic workup. Practice designing syntheses
for various compounds employing reactions studied to date. |
| 16.6 |
This section introduces a very important and pervasive mechanism for
reactions of carbonyl compounds. Be able to write a mechanism for attack
by a generic nucleophile on a carbonyl carbon under either basic or acidic
conditions. Be able to write the structure of the tetrahedral intermediate
that forms by nucleophilic attack under basic conditions, and the oxonium
ion that forms under acidic conditions prior to nucleophilic attack. In
both cases be able to write the structure of the final tetrahedral addition
product. |
| 16.7 |
Know the general structure for a hemiacetal and an acetal. Recognize
hemiacetals as being derived from aldehydes or ketones by reaction with
one molar equivalent of an alcohol, and ketals as being derived by reaction
of two molar equivalents of an alcohol with an aldehyde or ketone. Be able
to write a detailed mechanism for formation of either a hemiacetal or acetal,
under acidic or basic conditions. Note that these reactions are reversible.
Also note the practical importance of acetals as protecting groups for
aldehydes and ketones. Recognize the use of thioacetals as functional groups
that can be reduced to a CH2 group, thus providing a complementary
method to the Clemmensen and Wolff-Kishner reduction reactions. |
| 16.8 |
Know the general structure of an imine and how to form an imine by
reaction of a 1o amine with an aldehyde or ketone. Be able to
write a detailed mechanism for imine formation. Recognize that oximes,
hydrazones, and semicarbazides are simple extensions of the general reaction
for formation of an imine. Add the Wolff-Kishner reduction to your repertoire
as a reaction useful for converting aldehydes and ketones to CH2
groups (complementary to the Clemmensen and thioacetal reduction reactions). |
| 16.9 |
Recognize the addition of cyanide anion as an example of a nucleophilic
attack on a carbonyl group. Be able to write a mechanism for cyanohydrin
formation by overall addition of hydrogen cyanide to an aldehyde or ketone.
Note the importance of cyanohydrins as synthetic precursors of carboxylic
acids (by hydrolysis) and of primary amines (by reduction). |
| 16.10 |
Be able to write a general equation for the Wittig reaction. Recognize
the Wittig reaction as a method for alkene synthesis at the carbonyl carbon
of an aldehyde or ketone. Note that a mixture of E and Z
isomers may result. For a given alkene, be able to specify the starting
materials that would be required for its synthesis by a Wittig reaction. |
| 16.11 |
Know the Reformatsky reaction as a carbonyl addition reaction involving
an organometallic reagent, similar in principle to the Grignard reaction
and reactions of other nucleophilic organometallic reagents. Be able to
use the Reformatsky reaction for synthesis of beta-hydroxy esters. |
| 16.12 |
Recall methods for oxidizing aldehydes to carboxylic acids (Section
12.4D). Note the Baeyer-Villiger oxidation as a method for insertion of
an oxygen adjacent to an aldehyde or ketone carbonyl, but that the utility
of this method depends on the migratory aptitude of the groups involved. |
| 16.13 |
Note that the formation of hydrazone, oxime, and semicarbazone derivatives
of aldehydes and ketones (Sect. 16.8) typically results in solid products.
The melting point of these derivatives can be useful in identifying an
unknown aldehyde or ketone by comparison of the melting point for the derivative
of the unknown with the melting point of the derivative from a known aldehyde
or ketone. Note the oxidation of aldehydes to carboxylic acids by Ag(NH3)2+
in the Tollen's test. |
| 16.14A |
Know the typical frequency range in the IR spectrum for carbonyl stretching
absorptionsr. Note the effect that conjugation has on the IR frequency
of a carbonyl. |
| 16.14B |
Know the 13C NMR chemical shift regions for aldehyde and
ketone carbonyl carbons. Know the 1H NMR chemical shift regions
for hydrogens on carbons adjacent to carbonyl groups and for the hydrogen
of an aldehyde. Note typical characteristics of aldehydes and ketones in
mass and UV spectra. |
| Summary |
Use this section as a summary of addition reactions of aldehydes and
ketones. Note the similarities of the initial step in all addition reactions
of aldehydes and ketones. Try to generate your own specific examples for
each type of addition reaction. |
Assigned Problems: 1, 2, 3, 4abcef, 5, 6, 9, 10, 11, 12, 14, 15, 16, 17bcde,
21, 23b,c,d,e,k,o, 24, 28a,b,c,e-j,m,o,q, 31, 32, 34, 37, 39, 42, 46, 50
| Section |
Goals |
| 17.1 |
Be able to identify the a (alpha) and b
(beta)
hydrogens
of an aldehyde or ketone. Know that the a hydrogens
are weakly acidic. Be able to show the removal of an a
hydrogen to form a generic enolate anion. Also be able to show protonation
of an enolate to produce the corresponding keto and enol forms of the protonated
species. |
| 17.2 |
Be able to write both keto and enol forms for a specific aldehyde or
ketone. Know what the terms tautomer and tautomerization mean. Recognize
that keto-enol tautomerization is an equilibrium process that generally
favors the keto form. Note, however, the special stability of the enol
form in some b (beta)-dicarbonyl
compounds. |
| 17.3A |
Be able to write reactions, including mechanisms, for racemization
and epimerization of a stereocenter adjacent to a carbonyl by enolization
under either acidic or basic conditions. |
| 17.3B |
Note that the a carbon of an aldehyde
or ketone may become substituted by a halogen if the enol or enolate is
formed in the presence of molecular halogen species (X2). Be
able to write a mechanism for this process. |
| 17.3C |
Place the haloform reaction in the context of halogenation a
to a ketone carbonyl, as described in Sect. 17.3, recognizing that cleavage
to form a carboxylate ion and a haloform molecule tends to occur after
complete halogen substitution at the methyl group. |
| 17.4 |
Note that sections 17.4 - 17.7 involve the exceedingly important common
theme of an enolate or enol species attacking the carbonyl group of another
reactant to form an addition product. The aldol reaction is the foundation
example of this type of reaction. Learn to recognize the structural unit
of a b-hydroxy ketone or aldehyde, or an a,
b-unsaturated
ketone or aldehyde as likely being the synthetic product of an aldol reaction.
Be able to write a detailed mechanism for an aldol addition reaction and
the subsequent dehydration that frequently occurs (the aldol condensation
reaction). Note that an aldol addition reaction is an equilibrium reaction
and is thus reversible (retro-aldol), but that subsequent dehydration leads
to a very stable product due to conjugation of the alkene with the carbonyl
group. Note that for addition to a ketone carbonyl the aldol equilibrium
favors the reactants rather than the addition product. Be able to write
a detailed mechanism for an aldol condensation under acidic conditions.
Note the overall similarities with base-catalyzed aldol reactions described
above, but be able to use the enol form (vs. an enolate) as the nucleophile
and include the proper proton transfer steps. |
| 17.5, 5A |
Recognize that an aldol reaction between two different carbonyl compounds
(a crossed aldol reaction) can lead to a mixture of products. However,
if one compound has no enolizable hydrogens an aldol reaction between two
different compounds is practical. Be able to use an aldol reaction to synthesize
a given desired addition or condensation product. |
| 17.5B |
Be able to use the crossed aldol reaction with a ketone as the enolate
(the Claisen-Schmidt reaction) to synthesize conjugated enones (a,
b-unsaturated
ketones). Be able to write a detailed mechanism for this reaction. |
| 17.5C,D |
Note that hydrogens alpha to a nitro or nitrile group are also weakly
acidic, and that aldol-type condensations can occur when these compounds
are deprotonated and then attack an aldehyde or ketone. Be able to use
resonance structures to rationalize why hydrogens adjacent to nitro or
nitrile groups are weakly acidic. |
| 17.6 |
Appreciate that an intramolecular aldol condensation can be a very
good method for forming five- and six-membered rings of the appropriate
structure. Be able to recognize substructures that lend themselves to synthesis
by intramolecular aldol condensation. Be able to choose an appropriate
starting material and use the intramolecular aldol condensation for such
a synthesis. |
| 17.7 |
Know how to prepare LDA (lithium diisopropylamide) and use it
to form lithium enolate anions. Understand the difference between
a kinetic and a thermodynamic enolate. Be able to use lithium enolates
in directed aldol reactions and direct alkylation of ketones. |
| 17.8 |
Know how to make an a,
b-unsaturated
ketone through formation of an a-benzeneselenenyl
ketone followed by oxidation and intramolecular elimination. |
| 17.9, 9A |
Know the general pathways, in terms of site of nucleophilic attack
and product structure, for 1,2 and 1,4 addition to an a,
b-unsaturated
ketone or aldehyde. Be able to use resonance structures to rationalize
the positive charge and resulting electrophilic character at the b-carbon
of an a,
b-unsaturated
ketone or aldehyde. Be able to write a detailed mechanism for 1,4 addition,
showing the keto and enolate forms involved in the protonation step. Note
that cyanide, amines, and organocopper reagents are specific examples of
other nucleophiles that add to the b-carbon
of a,
b-unsaturated
ketones and aldehydes. |
| 17.9B |
Be able to use enolates as nucleophiles for attack at the b-carbon
of a, b-unsaturated
ketones and aldehydes (the Michael addition reaction). Note that this is
an important method for carbon-carbon bond formation and that it can be
combined in tandem with an aldol condensation for ring formation by the
Robinson annulation procedure. |
Assigned Problems: 1, 2, 3, 4, 7, 8, 9, 10, 12, 13, 15, 17, 18, 19, 21a,d,
25, 26a, 28a,b,c,d,e,f,g,j,k,l, 30a,c,e,f,g, 31a,b,d, 32, 33, 34, 35b,c,
44
| Section |
Goals |
| 18.1 |
Know the various ways in which a carboxyl group can be written in a
chemical structure. |
| 18.2A, B |
Be able to apply IUPAC nomenclature rules for naming carboxylic acids.
Know the common names for methanoic and ethanoic acid. Note for interest
the derivation of some common names for carboxylic acids. Recognize carboxylic
acids as polar substances with physical properties (e.g. bp, mp, and solubility)
that would be expected for relatively polar organic compounds. Know how
to name carboxylic acid salts. |
| 18.2C, D |
Know the relative acidity of carboxylic acids on the basis of their
typical pKa range. Recognize the importance of their
ready conversion to water soluble salts by reaction with bases. Note the
utility of this reaction for discriminating between phenols and carboxylic
acids on the basis of their reaction with hydroxide and bicarbonate bases.
Consider the role of inductive effects by substituents on the acidity of
a substituted carboxylic acid. |
| 18.2E-I |
Be able to recognize ester, carboxylic anhydride, acyl chloride, amide,
and nitrile functional groups and provide an IUPAC name for specific examples
of each type. |
| 18.2J |
Appreciate the importance of differences and trends in carbonyl IR
absorption frequencies for their use in structure identification of acyl
compounds. Know the 1H NMR chemical shift region for hydrogens
adjacent to acyl groups and for carboxylic acid hydrogens. Know the general
13C
NMR chemical shift region for acyl carbons, and recognize it as being distinct
from that for aldehydes and ketones. |
| 18.3 |
Recall the methods previously presented for synthesis of carboxylic
acids and be able to use each method for the synthesis of specific carboxylic
acid target molecules. Distinguish methods according to which maintain
the same length carbon chain, extend the carbon chain, of involve
bond cleavage between carbons. |
| 18.4 |
Be able to write a detailed mechanism for a generalized nucleophilic
addition-elimination reaction at a carbonyl group bearing a leaving group,
including the structure of the tetrahedral intermediate. Know which groups
typically act as leaving groups from acyl compounds, and the relative order
of reactivity with respect to these groups in an acyl substitution reaction.
Note that the various acyl compounds are derivatives of carboxylic acids. |
| 18.5 |
Recognize acyl chlorides (also called acid chlorides) as the most reactive
carboxylic acid derivative that we study. Know how to prepare an acyl chloride
from the corresponding carboxylic acid. Consider the mechanism for synthesis
of an acyl chloride using thionyl chloride. Note the variety of nucleophiles
that can react with acyl chlorides and the resulting functional group formed
by each one (including the reversion of an acyl chloride to the parent
carboxylic acid by reaction with water (hydrolysis) - a typically undesired
reaction). |
| 18.6 |
Know how to prepare a carboxylic acid anhydride. Note the reactions
of various nucleophiles with carboxylic anhydrides and the functional group
formed by each one (including the reversion of a carboxylic acid anhydride
to the parent carboxylic acid by reaction with water (hydrolysis) - a typically
undesired reaction). |
| 18.7 |
Know how to prepare an ester by acid-catalyzed esterification and be
able to write a detailed mechanism. Note also that the mechanism is under
equilibrium control, and therefore the reverse direction represents the
mechanism and overall reaction for acid-catalyzed ester hydrolysis.
Also know how to prepare an ester from either an acyl chloride or a carboxylic
acid anhydride. Know how to cleave an ester by base-promoted hydrolysis
(saponification) and be able to write a detailed mechanism. Recognize the
structures of g (gamma) or d
(delta) lactones as being intramolecular five- and six-membered ring esters,
respectively. Be able to write detailed mechanism for either lactone formation
(acid-catalyzed) or hydrolysis (under basic conditions). |
| 18.8 |
Know how to prepare an amide by reaction of an acyl chloride, carboxylic
anhydride, or by use of DCC. Recognize that amides can be formed from esters
and ammonium carboxylates but that these methods are not as useful synthetically.
Know how to hydrolyze an amide under acidic or basic conditions and be
able to write a mechanism for each process. Know how to prepare a nitrile
by dehydration of an amide. Note that nitriles can be hydrolyzed to carboxylic
acids. Be able to write a mechanism for either acidic or basic hydrolysis
of a nitrile to a carboxylic acid. Know that lactams are cyclic amides
(analogous to lactones as cyclic esters), and recognize the central importance
of the lactam functional group in penicillin antibiotics. |
| 18.9 |
Be able to prepare an a-halo carboxylic
acid. Note that a-halo carboxylic acids can
be useful reactants in nucleophilic substitution reactions. |
| 18.10 |
Know the general structure of the dialkyl carbonate and carbamate (urethane)
functional groups. Be able to prepare a dialkyl carbonate or carbamate
using an appropriate alkyl chloroformate. Also be able to prepare a carbamate
by reaction of an isocyanate. Note that reaction of amino groups with benzylchloroformate
to attach a benzyloxycarbonyl group is an important method for protecting
amino groups, especially in the chemical synthesis of peptides from amino
acids (as we shall see later in Section 24.7). Note the tendency for loss
of CO2 from those functional groups that share structural characteristics
with carbonic acid (vs. dialkyl carbonates and urethanes, which are stable
functional groups). |
| 18.11 |
Know that b-keto acids decarboxylate readily
upon heating. Be able to write a mechanism for this transformation starting
from either the acid itself or its carboxylate ion form. Note that decarboxylation
of b-keto acids will be an important aspect
of some reactions discussed in Chapter 19. |
| 18.12 |
Consider how the properties and reactivity of carboxylic acids and
functional groups derived from them can be used in chemical tests for acyl
compounds. Note that IR spectroscopy is an exceedingly useful qualitative
indicator of acyl functional groups (Section 18.2J), and that IR, NMR and
mass spectrometry can be used together to elucidate the complete structure
of a given compound. |
| Summary |
Use this section as an overall summary of the reactions of carboxylic
acids and their derivatives. Look for common themes among the reactions
and organize them for yourself according to these common attributes. Also
organize them for yourself according to methods of preparation for each
type of functional group. |
Assigned Problems: 1, 3a,e,f,g, 5a,b,d, 6a,e, 7a,b,d, 11, 12a(parts 3 and
4), 14, 16c, 17a,b,c, 19a,c,f,m, 20a,b,g,h, 21a,b, 23, 24a,c,d,e,f,i, 25b,c,d,e,
29a,b,e,f, 30a,b, 31, 32a, 34, 35, 36, 37, 38, 40, 45
