Functional Group Nomenclature & Reactions

Functional Group Nomenclature & Reactions
Alkanes
Alkane Nomenclature
Alkanes represent the simplest of the functional groups which are common in organic chemistry. An alkane contains only
carbon and hydrogen (a hydrocarbon) and contains only single bonds (termed a saturated hydrocarbon. Alkanes have the
general formula CnH2n+2, thus, an alkane with 10 carbons (n = 10) will have 2(10) + 2 = 22 hydrogens, or the molecular
formula C10H22.
The root, or parent name for an unbranched alkane is taken directly from the number of carbons in the chain according to a
scheme of nomenclature established by the International Union of Pure and Applied Chemistry (IUPAC), as shown
below:
Condensed Structure
Name
CH 4
methane
CH CH3 3
ethane
CH CH CH
3 2 3
propane
CH (CH ) CH
3 2 2 3
butane
CH (CH ) CH
3 2 3 3
pentane
CH (CH ) CH
3 2 4 3
hexane
CH (CH ) CH
3 2 5 3
heptane
CH (CH ) CH
3 2 6 3
octane
CH (CH ) CH
3 2 7 3
nonane
CH (CH ) CH
3 2 8 3
decane
CH (CH ) CH
3 2 9 3
undecane
CH (CH ) CH
3 2 10 3
dodecane
Hydrocarbons, however, are not restricted to linear, unbranched chains and there are often many possible orders in which a
hydrocarbon with a given molecular formula can be constructed. Compounds having the same molecular formula, which
differ in the order of attachment of the individual atoms, are called constitutional isomers. An example of the three possible
constitutional isomers of pentane (C5H12) are shown below.
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Although there are only three constitutional isomers for pentane, for alkanes having larger numbers of carbons, the number of
isomers is staggering; for C30H62, there are over 4 billion possible constitutional isomers.
In order to be able to communicate chemical information, it is essential to have a systematic set of rule defining nomenclature
for organic compounds. As mentioned previously, the IUPAC system of nomenclature accomplishes this and the rules for
naming linear and branched alkanes are given below:
 The IUPAC name for an alkane is constructed of two parts: 1) a prefix (meth... eth... prop..., etc.) which indicates the
number of carbons in the main, or parent, chain of the molecule, and 2) the suffix ...ane to indicate that the molecule
is an alkane.
 For branched-chain alkanes, the name of the parent hydrocarbon is taken from the longest continuous chain of
carbon atoms.
 Groups attached to the parent chain are called substituents and are named based on the number of carbons in the
longest chain of that substituent, and are numbered using the number of the carbon atom on the parent chain to
which they are attached. In simple alkanes, substituents are called alkyl groups and are named using the prefix for
the number of carbons in their main chain and the suffix ...yl. For example, methyl, ethyl, propyl, dodecyl, etc.
 If the same substituent occurs more than once in a molecule, the number of each carbon of the parent chain where
the substituent occurs is given and a multiplier is used to indicate the total number of identical substituents; i.e.,
dimethyl... trimethyl... tetraethyl..., etc.
 Numbering of the carbons in the parent chain is always done in the direction that gives the lowest number to the
substituent which is encountered first, or, the lowest number at the first point of difference. If there are
different substituents at equivalent positions on the chain, the substituent of lower alphabetical order is given the
lowest number.
 In constructing the name, substituents are arranged in alphabetical order, without regard for multipliers.
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For complex molecules, the IUPAC system of nomenclature can generate somewhat bewildering, and equally complex
nomenclature. This is further complicated by the fact that many common molecules are routinely referred to using simple
names which are descriptive of the molecule, or have arisen historically. The most common examples of these are the
substituent names for side-chains containing three to five carbons, where the prefixes iso..., sec-..., tert-..., and neo are
commonly used. The structures corresponding to these substituents are shown below:
Common Substituent Names:
-CH CH CH
2 2 3
propyl
-CHCH(CH ) 3 2
isopropyl
-CH CH CH
2 2 3
butyl
-CH CHCH(CH )
2 3 2
isobutyl
-CH(CH )CH CH 3 2 3
sec-butyl
-C(CH ) 3 3
tert-butyl
When these descriptors are used in an IUPAC name, iso is alphabetized normally; the hyphenated prefixes, however (sec-
and tert-) are disregarded when alphabetizing.
A more systematic method for the nomenclature of side-chains involves identifying the longest chain in the substituent,
numbering the substituent from the point of attachment to the parent, and indicating side-chains on the substituent using the
standard method described for simple alkanes. The name is enclosed in parenthesis to indicate that the numbering
corresponds to the local side-chain, not the parent chain. Thus:
 an isopropyl side-chain can also be named (1-methylethyl),

 a sec-butyl side-chain can also be named (1-methylpropyl),
 an isopentyl side-chain can also be named (3-methylbutyl), etc.
As a student of organic chemistry, you will encounter a variety of nomenclature conventions, and many non-standard names
in common usage must simply be learned. Systematic nomenclature, however, is important to clearly understand as these
methods are utilized in the cataloging of chemical information in print and computerized databases and effective information
retrieval requires a good working knowledge of these methods.
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The origin of the prefixes sec- and tert-, given above, rests with an attempt to describe the nature of the branched carbon unit.
By definition, a primary carbon is one which is attached to one other carbon atom, a secondary carbon is one which is
attached to two, a tertiary carbon is attached to three, and a quaternary carbon is attached to four other carbon atoms;
these are often abbreviated as 1o, 2o, 3o and 4o carbons.
Cycloalkane Nomenclature
The ability of carbon to form bonds with itself allows for the possibility of the formation of cyclic compounds. In nature,
cyclic compounds with ring sizes from 3 to 30 carbons are known; five- and six-member rings are especially common. For a
simple cycloalkane the general molecular formula is CnH2n, where n is the total number of carbons. You will note that this
differs from the general formula for an alkane (C nH2n+2) by the lack of the two additional hydrogens (the "+ 2 term"). As a
general rule, every ring which is constructed from an alkane reduces the number of hydrogens in the molecular formula for
the parent hydrocarbon by 2. Thus one ring gives C nH2n, two rings within the molecule would give a molecular formula of the
type CnH2n-2, three rings, CnH2n-4, etc. Thus by simply examining the molecular formula of an alkane or cycloalkane, you can
immediately calculate the number of rings within the molecule. This notion can be expanded to also include double bonds
(which also reduce the number of hydrogens in an alkane by two) to give the concept of degree of unsaturation, which is
covered in a later section. Using this simple calculation, the total number of rings and multiple bonds in a molecule can be
calculated, based simply on the observed molecular formula. Molecular models of cycloalkanes with n = 3 to 7 are shown
below. You should note that, in the smaller ring sizes (3, 4 and 5), the bond angles are significantly less than the optimal
109.5o. This results in a significant amount of ring strain in these compounds which make many small rings susceptible to
ring-opening reactions. The bond angles in a six-membered ring match well with the tetrahedral geometry of carbon and
there is virtually no ring strain in these compounds. Rings which are seven-membered and larger are highly distorted, and
again display significant ring strain.
The nomenclature for a simple cycloalkane is based on the parent hydrocarbon, with the simple addition of the prefix cyclo.
A three-membered ring is therefore cyclopropane, four-membered, cyclobutane, five-membered, cyclopentane, six-
membered, cyclohexane, etc.
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As a convenient shortcut, cyclic structures are usually drawn using line (structural or line-angle) drawings, as shown above.
Again, it is important to understand that every vertex in these drawings represents a -CH 2- group, every truncated line a -CH3
group and intersections of three or four lines represent 3o or 4o carbons, respectively.
Substituents on cycloalkanes are named using the conventions described for alkanes, with the exception that, on rings bearing
only one substituent, no number is needed; otherwise numbering proceeds to produce the lowest number at the first point of
difference.
Polycyclic carbons, such as those shown below, are common in organic chemistry. Carbons in these compounds which are
shared between attached rings are termed bridgehead carbons, and, in the special case where only one carbon is shared
between rings, the bridging carbon is referred to as a spiro carbon. Polycyclic compounds are named and numbered using a
complex system to indicate ring sizes and attachments, and will be covered later.
Conformations of Alkanes & Cycloalkanes

Structural formulas are useful for showing the attachment of atoms, and three-dimensional drawings are useful for showing
molecular shapes. Neither of these, however, conveys much information regarding the dynamics of molecular conformations
and the role that these play in controlling equilibrium shapes and reactivity of organic molecules.
As mentioned previously, there is generally free rotation around carbon-carbon single bonds. At room temperature, this
rotation can be quite rapid and can occur with a rate constant of 108 sec-1. For ethane, this rotation has only a small intrinsic
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energy barrier since the van der Waals radius of the hydrogen atoms on the adjacent carbons is sufficiently small so that
overlap is minimal. A movie file demonstrating this rotation is shown below:
(Click on the icon above to view the movie; use the BACK button to return to this page)
This can be contrasted, however, with rotation around the central carbon-carbon bond in butane, shown in the movie panel
below, in which two methyl groups clearly overlap during a single rotation (the van der Waals radii of the methyl hydrogen
atoms clearly overlap).
The rotation around the single bond in ethane, while not obviously hindered, does generate conformational isomers having
different potential energies. As shown above, as the dihedral angle between the ethane hydrogen atoms changes from 60 (a
staggered conformation) to 120 (an eclipsed conformation), the potential energy of the molecule increases by about 3
kcal/mole. As the methyl group continues to rotate towards 180 , the potential energy again drops and rises again as the next
eclipsed structure is formed.
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The effect of rotation on the potential energy of butane around the central carbon-carbon bond is more significant, as shown
above. The structure shown at 0o is fully eclipsed, that is, both methyl groups are aligned and are interacting maximally. As
the front methyl group is rotated 60 o, a gauche conformation is produced in which the methyl group is nestled between the
back methyl and the adjacent hydrogen atom. Another 60 o rotation produces an eclipsed version of the gauche conformation
which is approximately 2.4 kcal/mole less stable. At 180 o, the anti conformation is formed in which the two methyl groups
are on opposite faces of the molecule and no groups are eclipsed. This is the most stable confomer and it differs from the
fully eclipsed confomer by about 5 kcal/mole in potential energy. Further rotations regenerate an equivalent eclipsed gauche
conformer (at 240o), another gauche form (300o) and finally, the eclipsed form at 360 o. These rotations are best seen in a
movie clip which can be accessed by clicking on the icon below:
(Click on the icon above to view the movie)
Rotations such as these are not possible in cycloalkanes, where the ring constrains the movements around the carbon-carbon
single bonds. Cyclopropane rings are generally flat and have little conformational flexibility. The flexibility of four- and five-
membered rings is significantly greater and these molecules exist as a dynamic equilibrium among various "puckered"
conformations, as shown below.
The dynamic flexibility of a five-membered ring is best visualized in the movie clip (below) which simulates the equilibrium
interconversion of the various conformational isomers.
The conformational flexibility of cyclohexane is somewhat unique in that two equivalent structures are involved which are
linked by a process termed "ring inversion". As shown in the figure above, the lowest energy conformation of cyclohexane is
one in which each end of the molecule is "puckered", relative to the plane of the ring. This form is commonly called the
"chair conformation", as it somewhat resembles a reclined lawn chair. Inspection of this structure shows that there are two
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types of hydrogens in the molecule; a set that is perpendicular to the plane of the ring (axial hydrogens) and a set which are
more-or-less in the plane of the ring (equatorial hydrogens). The chemical reactivity of cyclohexane, however, is
inconsistent with two types of hydrogens in a stable form of the molecule (for example, there is only one
monochlorocyclohexane, not two, as would be predicted if axial and equatorial hydrogens could be replaced independently).
The explanation for this fact is that the flexibility of cyclohexane allows for rapid ring inversion, in which one chair
conformation is replaced by a second. Intermediate between these two chair forms is an unstable conformation called "boat
cyclohexane", in which both ends of the molecule are puckered in the same direction. The important thing to note about the
process of ring inversion is that during ring inversion, all axial substituents are converted to equatorial substituents,
and all equatorial substituents become axial. This process is difficult to visualize, initially, without the use of molecular
models, but can be seen easily in the movie clip below.
The axial hydrogens in cyclohexane experience a slight amount of steric repulsion. More bulky groups, however, can interact
strongly with other axial substituents, making it energetically unfavorable for these groups to occupy axial positions. These
unfavorable interactions can be seen below in the equatorial and axial representations of bromocyclohexane.
In the equatorial conformation, the bromine is "sticking out" from the plane of the ring and is experiencing only minimal
steric interactions with neighboring groups. In the axial conformation, however, the van der Waals radii of the bromine
significantly overlaps with that of the two axial hydrogens. This type of steric interaction can also be clearly seen in the
models for ethylcyclohexane, shown below.
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The full rotation of the ethyl group is also shown in the movie clip shown below.
As stated above, steric interactions tend to make conformations containing axial substituents energetically unfavorable,
relative to placing these substituents in equatorial positions. Since axial and equatorial groups in cyclohexane are linked via
equilibria involving ring inversion, the net effect is to force the equilibrium towards the more stable form in which the bulky
substituents are in equatorial positions, as shown below. For very large substituents (i.e., the tert-butyl group) this
equilibrium is so strongly shifted so that ring inversion essentially never occurs. Such groups are said to "lock" the ring into
the energetically favorable conformation.
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Alkenes and Alkynes
Alkene Nomenclature
Alkenes represent one of the most common functional groups in organic chemistry. An alkene contains only carbon and
hydrogen (a hydrocarbon) and contains at least double bond (termed an unsaturated hydrocarbon. Alkenes have the
general formula CnH2n, thus, an alkene with 10 carbons (n = 10) will have 2(10) = 20 hydrogens, or the molecular formula
C10H20; each double bond therefore contributes one degree of unsaturation.
The root, or parent name for an unbranched alkene is taken directly from the number of carbons in the chain according to a
scheme of nomenclature established by the International Union of Pure and Applied Chemistry (IUPAC), as described
previously for alkanes.
To name alkenes:
1. Find the longest chain containing the alkene
The IUPAC name for an alkene is constructed of two parts: 1) a prefix (meth... eth... prop..., etc.) which indicates the number
of carbons in the main, or parent, chain of the molecule, and 2) the suffix ...ene to indicate that the molecule is an alkane.
For branched-chain alkanes, the name of the parent hydrocarbon is taken from the longest continuous chain of carbon atoms
containing the double bond.
2. Number the chain, giving the double bond the lowest possible number.
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Numbering of the carbons in the parent chain is always done in the direction that gives the lowest number to the double
bond, or, the lowest number at the first point of difference. If there are different substituents at equivalent positions on the
chain, the substituent of lower alphabetical order is given the lowest number.
If the same substituent occurs more than once in a molecule, the number of each carbon of the parent chain where the
substituent occurs is given and a multiplier is used to indicate the total number of identical substituents; i.e., dimethyl...
trimethyl... tetraethyl..., etc. In constructing the name, substituents are arranged in alphabetical order, without regard for
multipliers.
3. For cycloalkenes, begin numbering at the double bond and proceed through the double bond in the direction to
generate the lowest number at the first point of difference.
One of the most common mistakes in naming cycloalkenes is to generate the lowest number sequence around the ring,
disregarding this rule. Once again, the numbering must begin at the double bond and proceed through the bond in the
direction to generate the lowest number sequence.
4. Assign stereochemistry using the E-Z designation
Historically, alkenes have been named using cis- and trans- to represent stereochemistry around the double bond; cis- for
compounds where the "main substituents" are on the same side of the double bond, and trans- when they are on opposite
sides. This system clearly breaks down, however, in more complex molecules where decisions concerning the "main
substituents" are not easily made, and the E-Z system provides a set of rules to aid in these decisions. You will see later that
these same rules are used in assigning priorities for determining absolute configuration in chiral molecules.
The rules for assigning E-Z designations are as follows:

1. rank atoms directly attached to the double bond according to their atomic number
2. if there is a "tie" at any substituent, look at the second, third, etc., until a difference is found
3. multiple bonds count as multiples of that same atom
4. if the highest priority groups are on the same side of the double bond, the molecule is Z; if the highest priority
groups are on opposite sides, the molecule is E
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Calculating Degrees of Unsaturation
Because of the presence of a double bond, alkenes have two fewer hydrogens than the corresponding parent hydrocarbon. For
example, ethene (H2C=CH2) has the molecular formula C2H4 and ethane (CH3CH3) has the formula C2H6 (following the 2n + 2
rule). Cycloalkanes, likewise, have two fewer hydrogens than the parent hydrocarbon since two of the valences are utilized to
close the ring: cyclohexane is C6H12, while hexane is C6H14.
Knowing this relationship, it is possible to take a molecular formula and calculate the degree of unsaturation; that is, the
total number of multiple bonds or rings in a molecule. This information can then be utilized in the conversion of
analytical data into structural possibilities.
For hydrocarbons, the process is simple:
 take the parent hydrocarbon and calculate the number of hydrogens using the 2n + 2 rule,
 every two hydrogens that are "missing" in the analysis of the unknown represents one degree of
unsaturation.
C6H12 is 2 short of C6H14

1 DU
C4H6 is 4 short of C4H10 2 DU
2 DU

6 DU Count the rings!
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5 DU
For compounds containing elements other than carbon and hydrogen, degrees of unsaturation can be calculated as follows:
 Organohalogen compounds: since a halogen is simply a replacement for a hydrogen in an organic molecule (a
valence of one), you simply add the total number of halogens to the carbon-hydrogen analysis, and calculate the
unsaturation number as described above.
 Organooxygen compounds: since oxygen is divalent, it has no effect on the calculation for the degree of
unsaturation, and can be simply ignored. This can be demonstrated by considering ethanol (CH 3CH2OH); removing
the oxygen produces ethane (CH3CH2-H). The calculation for ethanol (ignoring the oxygen) therefore gives no
degrees of unsaturation. For a carbonyl, (i.e., acetone, CH3COCH3), ignoring the oxygen gives C3H6, two hydrogens
short of (2n + 2), and one degree of unsaturation. The carbonyl is therefore equivalent to one degree of unsaturation.
 Organonitrogen compounds: since nitrogen is trivalent, on organonitrogen compound has one more hydrogen than
an equivalent hydrocarbon has, and therefore you should subtract the number of nitrogens from the total
number of hydrogens and calculate as described above.
Some examples:
C6H10O "C6H10" which is 4 short of C6H14 2 DU
C5H9N "C5H8" which is 4 short of C5H12 2 DU
C6H1?N "C6H12" which is 2 short of C6H14 1 DU
C6H13N4 "C6H8" which is 6 short of C6H14 3 DU
C8H8O "C8H8" which is 10 short of C8H18 5 DU
Each of the six rings in this molecule is shown in a separate color. Note that, when counting rings in a polycyclic compound,
you are not allowed to retrace any path, only to connect atoms following new paths.
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Addition of HX or X to Alkenes 2
Addition of Halogen Acids to Alkenes
The addition of halogen acids to alkenes is a stepwise process which generally involves a solvent-equilibrated carbocation
intermediate. The formation of this intermediate is initiated through a simple acid-base equilibrium in which the halogen acid
donates a proton to the alkene -system, which is functioning as a Lewis base. The protonated -system has a short lifetime
and can rapidly revert to starting materials, or can rearrange from a (cationic) protonated -bond, to an sp3 sigma bond
adjacent to an sp2 carbocation center. If the alkene is unsymmetrical, the protonated -cloud intermediate can break down by
two pathways, as shown below, to potentially form carbocations having differing ground-state energies. The reaction
pathways leading from this intermediate to the two carbocations will differ in energy, and, in general, the pathway leading
to the more stable intermediate will be of lower energy, and will be the preferred pathway.
The resulting carbocation is formed on the carbon of the alkene which is best able to stabilize the cationic center. In
simple unstrained non-conjugated systems, without adjacent heteroatoms, the order of stability of carbocations will be
tertiary > secondary > primary. Since tertiary centers have no attached hydrogens, secondary centers have one and primary
centers have two, there is an apparent inverse relationship between the "number of attached hydrogens" and the likelihood
that the carbocation will form at that center. This is the origin of Markovnikov's Rule, which states that...
...in the addition of HX to an alkene, the proton will attach to the center having the greatest number of hydrogens...
often restated as "them that has, gets". While the rule is a useful guide, you should remember that the selectivity is
actually to place the carbocation on the carbon which can best stabilize the charge.
Once the carbocation is formed, the most favorable reaction will involve the addition of a nucleophile to form an sp 3 center.
In the reaction with halogen acid (HCl and HBr), the most nucleophilic molecules in the system will be the chloride and
bromide anions. Attack of these on the planar (sp 2) carbocation can occur from either above, or below the plane defined by
the sp2 center, and the net addition of HX can therefore occur either syn or (cis; on the same side) or anti (trans; on the
opposite side), relative to the hydrogen atom.
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Radical Addition of HBr to Alkenes
The addition of HBr to alkenes in the presence of peroxides converts the alkene into an alkyl bromide. The overall addition of
HBr to the double bond is anti-Markovnikov, with the bromine being bonded to the alkene carbon which would form the
least stable carbocationic center. The reaction involves attack of bromine radical to generate a radical on one of the alkene
carbons. The selectivity arises due to the tendency to direct addition in order to form the most stable radical intermediate;
rearrangements do not occur. In the example shown below, the reaction is initiated by the addition of bromine radical to the
alkene in the cyclohexene ring to form a radical intermediate. The bromine bonds to the secondary carbon since this leaves
the more stable tertiary radical on carbon (radical stability largely parallels carbocation stability). In a second step, this
tertiary radical picks up a hydrogen atom (from HBr) to give the final product. Since the radical is planar, as shown above for
carbocations, there is no stereochemical preference in the addition reaction.
Addition of Halogen to Alkenes
The addition of halogen to alkenes is a stepwise process involving a "halonium" ion intermediate. The formation of this
intermediate is initiated through attack of halogen on the alkene -system, to form the cyclic halonium ion (i.e., bromonium
or chloronium ion) and expel the halogen anion (i.e., bromide or chloride). This intermediate is highly electrophilic and reacts
rapidly with the best nucleophile in the system; that is, the halide anion expelled in the previous step. Since the halonium ion
effectively blocks attack by halide on the same side, attack must be come from the backside (relative to the large halogen
atom) to form the trans-1,2-dihalide. This is demonstrated below for the addition of bromine to 1-propene. The large bromine
on the intermediate bromonium ion (shown as a space-filling overlay) effectively blocks attack from the top, forcing the
addition to be anti (trans; from the opposite side).
Sample Reactions:
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Predict the major organic product for each of the following reactions. Be sure to show stereochemistry, when appropriate,
and to draw the final product in it's most stable conformation.
Click on any reaction to check your answer.
Addition of HX to alkenes converts the alkene into an alkyl halide. The overall addition of HCl to the double bond follows
the Markovnikov convention, with the bromine being bonded to the most stable carbocationic center. The reaction generally
involves a carbocation intermediate and rearrangements are possible. Since this reaction would represent addition of bromide
anion to a secondary carbocation in a molecule containing no tertiary carbons, a rearrangement is unlikely.
Addition of HBr to alkenes in the presence of peroxides converts the alkene into an alkyl bromide. The overall addition of
rearrangements do not occur.
Addition of halogen to alkenes converts the alkene into a trans-1,2-dihalide. The reaction involves initial addition of bromine
to the alkene -cloud, followed by backside attack of bromide to form the trans-1,2-dibromide. In the initially formed
addition product, both of the bromines must be di-axial; the structure shown above shows the ring-inversion product in which
both halogens are in the equatorial positions.
anion to a tertiary carbocation, no rearrangement is observed in the present instance.
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Addition of halogen to alkenes converts the alkene into a trans-1,2-dihalide. The reaction involves initial addition of chlorine
to the alkene -cloud, followed by backside attack of chloride to form the trans-1,2-dichloride. In the initially formed
addition product, both of the chlorines must be di-axial; the structure shown above shows the geometry in which both
halogens are re-positioned to generate the least amount of ring-strain.
Addition of halogen to alkenes converts the alkene into a trans-1,2-dihalide. The reaction involves initial addition of bromine
to the alkene -cloud, followed by backside attack of bromide to form the trans-1,2-dibromide. In the initially formed
addition product, both of the bromines must be trans-coplanar; in the structure shown above, there is no stereochemistry.
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Reactions of Alkynes
Addition of Halogen Acids to Alkenes
The addition of halogen acids to alkynes is a stepwise process which generally involves a solvent-equilibrated carbocation
intermediate. The formation of this intermediate is initiated through a simple acid-base equilibrium in which the halogen acid
donates a proton to the alkyne -system, which is functioning as a Lewis base. The protonated -system has a short lifetime
and can rapidly revert to starting materials, or can rearrange from a (cationic) protonated -bond, to an sp2 sigma bond
adjacent to an sp2 carbocation center. If the alkyne is unsymmetrical, the protonated -cloud intermediate can break down by
two pathways to potentially form carbocations having differing ground-state energies. The reaction pathways leading from
this intermediate to the two carbocations will differ in energy, and, in general, the pathway leading to the more stable
intermediate will be of lower energy, and will be the preferred pathway. The resulting carbocation is formed on the
carbon of the alkyne which is best able to stabilize the cationic center. In simple unstrained non-conjugated systems,
without adjacent heteroatoms, the order of stability of carbocations formed from alkyne protonation will be secondary >
primary. Since secondary centers have no attached and primary centers have one, there is an apparent inverse relationship
between the "number of attached hydrogens" and the likelihood that the carbocation will form at that center and this is
another example of Markovnikov's Rule, which was described for alkenes.
Once the carbocation is formed, the most favorable reaction will involve the addition of a nucleophile to form a vinyl halide
intermediate. This alkene can now undergo a second protonation step, just like any other alkene, except that the carbocation
will always be formed on the carbon bearing the halogen, since this carbocation is now stabilized by resonance with the
halonium ion. The final result of the addition is that two moles of halogen halide are added, to give a 1,1-dihalide.
Addition of Halogen to Alkynes
The addition of halogen to alkynes is a stepwise process involving a "halonium" ion intermediate. The formation of this
intermediate is initiated through attack of halogen on the alkyne -system, to form the cyclic halonium ion (i.e., bromonium
or chloronium ion) and expel the halogen anion (i.e., bromide or chloride). This intermediate is highly electrophilic and reacts
rapidly with the best nucleophile in the system; that is, the halide anion expelled in the previous step. Attack by halide
generates a vinyl halide, which is an alkene and can undergo a second addition of halogen. The final product of the reaction is
therefore a 1,1,2,2-tetrahalide.
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Addition of Water to Alkynes
The mercury-catalyzed addition of water to alkynes is another example of a stepwise process which generally involves a
solvent-equilibrated carbocation intermediate. The formation of this intermediate is initiated through a simple acid-base
equilibrium in which the mercury ion interacts with the alkyne -system, which is functioning as a Lewis base. The chelated
>-system rearranges to form an sp2 sigma bond adjacent to an sp2 carbocation center. If the alkyne is unsymmetrical, two
carbocations are possible and the addition will proceed to form the most stable carbocation. As before, secondary centers
will be favored over primary, and overall addition of water will follow the order predicted by Markovnikov's Rule. Addition
of water forms a vinyl alcohol, which is termed an "enol". Enols are unstable compounds which rapidly interconvert with the
corresponding carbonyl compound. Hence, the final product of the hydration reaction is the formation of an aldehyde or
ketone, with the oxygen bonded to the carbon of the alkyne which would ultimately yield the most stable carbocation.
Hydroboration of Alkynes
The reaction of BH3 with an alkyne begins with the Lewis acid chelation of the alkyne -system by the boron. This complex
then rearranges in a more-or-less concerted manner to produce the vinyl borane. The reaction seems to be dominated by steric
effects and the boron attaches to the least hindered carbon. All three equivalents of the boron hydride can be utilized in
separate reactions to give a trivinyl borane. The organoborane which is formed can be oxidized by alkaline peroxide to form
the alcohol by a mechanism which involves attack of peroxide anion on the boron, followed by alkyl migration to the oxygen,
with loss of hydroxide anion. The resulting borate ester is rapidly hydrolyzed by the alkaline conditions to form an "enol".
19
Rearrangement of the enol to the corresponding carbonyl compound yields an aldehyde or ketone, with the oxygen bonded to
the carbon of the alkyne which would generally yield the least stable carbocation (generally, anti-Markovnikov addition).
Reduction of Alkynes
Catalytic hydrogenation of alkynes with H2 and a standard catalyst (Pt or Pd supported on charcoal, etc.) produces the
corresponding alkane. However, partial reduction of an alkyne to an alkene is possible using a "poisoned catalyst", such as Pd
or Pt on BaSO4, or with the "Lindar Catalyst". In these reactions, addition of hydrogen is syn (cis) to yield the cis alkene. The
transfer of hydrogen occurs in a strictly cis manner, probably due to the geometric constraints of the metal surface. The
detailed mechanism is not trivial, and probably involves several metal-carbon bonded species.
Alkynes can also be partially reduced to trans-alkenes using a "dissolving metal reduction", in which the alkyne is formed by
a radical mechanism in the presence of Li or Na metal dissolving in liquid ammonia. Please note that this differs from the
base sodium amide, which is formed from sodium metal previously dissolved in liquid ammonia.
Oxidation of Alkynes
Acidic potassium permanganate is a powerful oxidant towards organic molecules and will readily cleave alkynes. Alkyne
carbons are converted into carboxylic acids in this reaction.
20
Alkynes Anions as Nucleophiles
Terminal alkynes are slightly acidic and a powerful base such as sodium amide (sodium previously dissolved in liquid
ammonia) will react with these compounds to give alkyne anions, which are powerful nucleophiles. The most common
reaction in which these nucleophiles are utilized involves reaction with alkyl halides to displace the halogen and form a new
alkyne with a longer carbon chain. The mechanism of this reaction, an S N2 reaction, will be discussed in detail in the chapter
under alkyl halides.
Alkyl Halides; Substitution & Elimination Reactions
Nomenclature of Alkyl Halides

Simple alkyl halides are named as substituents on the parent alkane, using chloro, bromo, iodo or fluoro to denote the
nature of the halogen.
1. First, select the longest continuous carbon chain; if the molecule contains a double or triple bond, the parent chain
must contain it.
2. Number the carbon chain in the direction to produce the lowest number for the first substituent encountered, or to
give the lowest number sequence at the first point of difference.
3. Number the substituents and write the name, listing substituents alphabetically.
Several simple examples are shown below:
21
In the first example, the parent chain is a hexane and a bromine is attached to carbon #3. If we had started numbering at the
other end, the bromine would be in position #4; hence the name, 3-bromohexane.
In the second example, there are two potential five-carbon chains; in this case, the chain with the most substituents is
selected as parent, (a pentane). Attached to the pentane at carbon #2 is a bromo group and at carbon #3, an ethyl group;
hence the name 2-bromo-3-ethylpentane.
In the third example, the iodine is attached to a cyclohexane ring and will therefore be named as a halocycloalkane; the name
is iodocyclohexane (no number required).
In the last example, the chlorine and two methyl groups are attached to a cyclopentane ring. The numbering must begin at the
carbon bearing the methyl groups since the sequence [1,1,2] is lower at the first point of difference than the sequence [1,2,2],
which you would have if the chlorine was attached to carbon #1; the name is therefore 2-chloro-1,1-dimethylcyclopentane.
Nucleophilic Substitution Reactions

As described previously, the carbon-halogen bond in alkyl halides is polarized, placing a partial positive charge on the
carbon, and a partial negative charge on the halogen. The partially positive carbon is therefore electrophilic and will be
susceptible to attack by nucleophiles. When a suitable nucleophile attacks an alkyl halide, it can displace the halogen in a
substitution reaction to release the halide anion and form a new bond to the carbon, as shown below.
With simple primary alkyl halides reacting with simple nucleophiles, the rate at which this substitution reaction proceeds is
proportional to both the concentration of the nucleophile and the concentration of the reactant alkyl halide, making the
reaction second order. This type of second-order, nucleophilic displacement reaction is therefore termed an "S N2" reaction
(substitution, nucleophilic, bimolecular). The mechanism for this reaction is best described as concerted with the reaction
coordinate passing through a single energy maximum with no distinct intermediate. The transition state for this reaction is
described by the structure shown below in which partial bonds exist between the central carbon and the attacking nucleophile
and departing halogen. An animation of this process also appears below.
22
The geometry of this transition state, with the planar carbon in the center, requires that the central
carbon undergo a stereochemical inversion; therefore if the central carbon is chiral, the absolute
configuration of the central carbon must change. In the example shown below, R-2-bromobutane reacts
with bromide anion to form the enantiomer, S-2-bromobutane.
Predicting the product from these types of substitution reactions simply requires that the bond to the halogen leaving group
be broken and a new bond be made between the nucleophilic atom and the central carbon, inverting the absolute
configuration if appropriate.
SN2 reaction mechanisms are also involved in two common procedures which can be utilized to prepare alkyl halides from
alcohols; that is reaction with PBr 3 and with SOCl2. In the reaction with PBr 3, an intermediate phosphite ester is formed,
which undergoes SN2 displacement with bromide anion to give the alkyl bromide with inversion of configuration.
Thionyl chloride reacts by a similar mechanism involving a sulfite ester in polar solvents (i.e., pyridine), but can undergo an
unusual SNi mechanism in non-polar solvents (benzene) to give the alkyl chloride with retention of configuration (this
involves an unusual frontside attack, but is worth remembering since the pair of reactions gives you stereochemical control
over the generation of an alkyl chloride).
23
Unlike primary alkyl halides, when most tertiary alkyl halides react with simple nucleophiles, the rate at which the
substitution reaction proceeds is proportional only to the concentration of the alkyl halide, making the reaction first order.
This type of first-order, nucleophilic displacement reaction is therefore termed an "S N1" reaction (substitution, nucleophilic,
unimolecular). The mechanism for this reaction is best described as stepwise with the involvement of a carbocation
intermediate. The rate limiting step for this reaction is the spontaneous breaking of the carbon-halogen bond to form the
carbocation, and the reaction with the nucleophile is generally fast. Since only the alkyl halide is present in the rate-limiting
transition state, only alkyl halide concentration will effect the rate.
Since carbocations are involved, the reaction is prone to rearrangement, which may involve hydride shifts, alkyl group shifts
or skeletal rearrangements.
24
The most significant factor in determining whether a given substitution reaction will follow an S N1 or an SN2 mechanism is
the nature of the reactant; the more stable the potential carbocation, the more likely an S N1 mechanism becomes. Therefore,
primary alkyl halides will generally follow "pure" S N2 pathways, tertiary alkyl halides will generally follow S N1 pathways,
and secondary alkyl halides may follow either, depending on the exact nature of the compound.
Elimination Reactions
As described previously, primary alkyl halides generally undergo substitution reactions with simple nucleophiles by an S N2
mechanism. Secondary alkyl halides, often react with simple basic nucleophiles to give a mixture of products arising from
both substitution and elimination.
As with substitution reactions, the rate at which elimination reactions proceed can be proportional to both the concentration
of the base and the concentration of the reactant alkyl halide (an "E2" reaction (elimination bimolecular), or the rate can be
proportional only to the alkyl halide (an "E1" reaction (elimination unimolecular). The mechanism for the E2 reaction is best
described as concerted with the reaction coordinate passing through a single energy maximum with no distinct intermediate.
The transition state for this reaction is described by the structure shown below in which partial bonds exist between the
attacking base, the hydrogen which is abstracted, and departing halogen.
The geometry of this transition state requires that the halogen be anti and coplanar with the hydrogen which is being
removed (also termed "antiperiplanar"). This fact is important to remember since the stereochemistry of the resulting alkene
(Z or E; cis or trans) is often controlled by the hydrogen which is removed in the elimination reaction.
25
In the reaction shown below, the hydrogen on the carbon bearing the methyl group cannot become anti-to the halogen, hence
the elimination occurs on the secondary carbon, to give the unfavored less substituted alkene.
The rate-limiting transition state in the E1 reaction is again, carbocation formation, and the transition state is generally
described as shown below. Factors which control whether E1 or E2 mechanisms will be observed again relate simply to the
stability of the intermediate carbocation.
Control of the reaction pathway between substitution and elimination is generally accomplished by careful choice of the
reactants; strong, sterically hindered bases tend to favor elimination, while weak, unhindered nucleophiles tend to favor
substitution. The choice for a "strong, hindered base" is generally tert-butoxide anion in tert-butanol as solvent, and it is
generally safe to assume that a potential substitution/elimination reaction showing these conditions will proceed with
elimination.
26
Conjugated Dienes
Conjugated Dienes: Introduction & Nomenclature

Compounds containing more than one double bond are said to be conjugated if they posess a series of adjacent sp2 centers. In
a compound such as this, the adjacent p-orbitals overlap to form a continuous -system, as seen in the graphic below.
Polyenes are named as are simple alkenes, using the multipliers di-, tri-, etc. to indicate the number of double bonds and
numbers to show their positions.
As with simple alkenes:
27
1. Find the longest chain containing the double bonds; the name of the parent hydrocarbon is taken from the longest
continuous chain of carbon atoms containing the double bonds.
2. Number the chain, giving the double bonds the lowest possible number; use multipliers to indicate the total number of
double bonds (di, tri, tetra, etc.) Recall that in constructing the name, substituents are arranged in alphabetical order, without
regard for these multipliers.
3. For cycloalkenes, begin numbering at one double bond and proceed through the double bond in the direction to generate
the lowest number at the first point of difference.
4. If appropriate, assign stereochemistry using the E-Z designation.
The rules for assigning E-Z designations are as follows:
1. rank atoms directly attached to the double bond according to their atomic number
2. if there is a "tie" at any substituent, look at the second, third, etc., until a difference is found
3. multiple bonds count as multiples of that same atom
4. if the highest priority groups are on the same side of the double bond, the molecule is Z; if the highest priority
groups are on opposite sides, the molecule is E
Examples:
Conjugated Dienes: Ionic Addition Reactions

When compounds containing conjugated double bonds undergo typical ionic alkene addition reactions (addition of HBr or
Br2, for example), the products which are obtained are not those which would be expected for addition to the individual
double bonds in the molecule. For the addition of HBr to 1,3-butadiene, two products are obtained, 3-bromo-1-butene and 1-
bromo-2-butene. These products can be seen to arise from a "standard" 1,2-addition to one of the terminal double bond
(Markovnikov-style), and from a 1,4-addition of HBr to the two terminal carbons, with relocation of the double bond onto the
central two carbons.
The formation of these products can be readily understood by examining the mechanism of the addition reaction. Protonation
of the conjugated diene on either terminal carbon will generate a carbocation on the adjacent secondary carbon. This
carbocation, however, can be stabilized by resonance with the adjacent double bond to give a delocalized carbocation (an
allylic carbocation) in which there is positive character on both a secondary center and on the terminal, primary
carbon. Since both of these centers share positive character in the resonance hybrid, both are subject to nucleophilic attack
by bromide anion; attack on the secondary carbon gives the 1,2-addition product, and attack on the terminal carbon gives the
1,4-addition product.
28
Some further observations on this reaction reveal the following:
 The 1,2- addition product forms rapidly at low temperatures;

 the 1,4-addition product is predominant at higher temperatures;
 even at low temperatures, 1,4-addition products will predominate if given enough time;
 the addition of HBr to butadiene is reversible and isolated 1,2-addition product will convert to the 1,4-product at
higher temperatures or at longer times.
These data can be explained using the reaction coordinates shown below. The pathway to form the 1,2-product must have a
lower activation energy, because it forms more rapidly than the 1,4-product. The 1,4-product, however, must be more stable
than the 1,2-product because it accumulates at equilibrium (note that the reaction appears freely reversible, since isolated 1,2-
product reverts to 1,4-, given enough time).
The 1,2-addition product is referred to as the kinetic product since it is formed faster. The 1,4-product is the
thermodynamic product since it is thermodynamically more stable. A similar product distribution is observed for Br 2
addition, through a similar mechanism.
Conjugated Dienes: Cycloaddition Reactions

29
Conjugated dienes react with alkenes to yield cyclohexene derivatives. The reaction is termed a 4+2 cycloaddition and is
generally referred to as the Diels-Alder Reaction. The reactants in the cycloaddition are referred to, generically, as a diene
and a dienophile. The reaction usually requires heat and pressure to give good yields and is promoted by electron
withdrawing groups on the dienophile and electron donating groups on the diene.
The mechanism of the reaction is generally described as concerted involving an electrocyclic transition state in which the
two new sigma bonds form simultaneously; this is usually represented by showing the electron movement with "curved
arrows", as shown above. Since both bonds form at the same time, it is necessary for the diene to be in the proper
conformation prior to the reaction, that is, the s-cis conformation is required, and dienes which cannot adopt this
conformation will not react.
Examination of the animation shown above for the reaction of ethene with butadiene clearly shows that the initial product of
the reaction is the boat cyclohexene. This can also be appreciated by examination of the sequence of images shown below
for the reaction of butadiene with butenedinitrile. Lining up the reacting centers and allowing the cycloaddition to proceed
generates the structure shown on the right. Rotating this along the X-axis (with the double bond remaining in the back) shows
the compound in the "boat" conformation. Converting this to a "chair" by rotating one end down (and rotating the molecule
slightly along the Z-axis) gives the middle image on the second row, which is an idealized cyclohexene "chair". In fact, the
geometry of the double bond contorts the molecule as shown on the right, but the idealized chair is useful to establish
stereochemical relationship between substituents on the diene and dienophile, as they appear in the cyclohexene product.
30
...rotate along the x-axis to give the intermediate "boat"...
Following a similar sequence of steps to those shown above, the product of the reaction of trans-trans-2,3-hexadiene with
trans-2-butene can be shown to be the tetramethyl cyclohexene shown below. Using the numbering scheme shown (the
corresponding numbers are also shown on the reactants), the methyl groups of the diene are 1,4-relative to each other and
they are cis- (one is axial, one is equatorial). The methyl groups of the dienophile are 1,2-relative to each other (2,3- in the
molecule) and they are trans- (both are equatorial).
A general rule can be established, as shown below, that the stereochemistry of the dienophile is retained and that a trans-
trans-diene yields cis-substituents, while a cis-trans-diene yields trans-substituents (a cis-cis-diene will not react since it
cannot achieve the s-cis conformation).
31
One further aspect of cycloaddition stereochemistry; when a bicycloheptane ring is formed in the cycloaddition (i.e., when
cyclopentadiene or furan is the reacting diene), the preferred orientation of the substituents from the dienophile will be endo
(facing into the cavity of the cyclohexene boat).
Arenes
Arenes: Nomenclature
Monosubstituted benzene derivatives are names as other hydrocarbons using the following set of rules:
1. Benzene is the parent name; when a benzene ring is a substituent on another chain, it is referred to as a "phenyl"
group.
2. Disubstituted benzenes are named using ortho-, para- and meta- to describe the substitution pattern (1,2 1,4 and 1,3
respectively) or simply by numbering the substituents.
32
3. Substituents are numbered to give the lowest possible number sequence at the first point of difference, assigning
priorities alphabetically if there is a "tie".
There are also a large number of common (or "trivial") names for arenes which are in common usage and students should
strive to recognize these by both systematic and common names.
Many of these are acceptable "parents" with regard to nomenclature. When one is these is used as the parent chain, the
substituent is position #1, by definition.
33
More Examples:
Arenes: Aromatic Systems and the 4n+2 Rule

Benzene, having the molecular formula C 6H6, would be consistent with a structure such as cyclohexatriene, having three
conjugated double bonds in a six-membered ring. The compound is, however, far more stable than would be predicted for a
triene, based on the heat of hydrogenation (the energy evolved when one mole of compound is reacted with H 2 in the
presence of Pt or Pd catalyst. As shown below, the inclusion of additional double bonds in a compound is generally
associated with an increase in the heat of hydrogenation of approximately 25 kcal/mole; benzene, however, has a heat of
hydrogenation which is less than that of cyclohexadiene. Further, benzene does not undergo "typical" alkene reactions; it will
not react with Br2 to form a dibromide, nor will it react with halogen acids (i.e., HCl) to give alkyl halides.
The rationalization for the unusual reactivity of benzene which is generally accepted today is that the conjugated system
forms a continuous molecular orbital above and below the plane of the ring, and that this planar, continuous system
containing six electrons has unusual stability. The delocalization of the electrons is typically shown by writing resonance
forms in which the double bonds in benzene compounds can be shown to be distributed equally among all carbon centers
(shown below for dibromobenzene). Remember that resonance forms represent structural limits and that the molecule is
"never" one form or the other, but is a hybrid of both. To show this, the bonding in benzene compounds is often written as a
circle within the ring, although this type of structural representation has its own drawbacks, as we will see when we consider
substitution reactions.
34
The formation of the molecular orbital can be seen below, as the overlap of the six p-orbitals to form the continuous
system.
The resonance description of benzene explains the geometry of the molecule but does not explain the unusual stability of
benzene and its derivatives. The stability of benzene is suggested to arise from the fact that the conjugated system is
planar and contains 4n + 2 electrons (with n = 1), and it is suggested that all compounds having planar, conjugated ?
systems containing 4n + 2 electrons will share this stability. This property, described originally by Huckel, is referred to as
aromaticity. Aromaticity, and unusual stability, will therefore be associated with molecules having 6 (n = 1), 10 (n = 2), 14
(n = 3), 18 (n = 4), etc., electrons. Unshared pairs of electrons on heteroatoms within the ring can also be counted to achieve
aromaticity, as shown in the examples below:
It is also essential that the carbon skeleton be planar, as shown for cyclodecapentaene, which has 10 electrons, but is not
aromatic because the ring hydrogens force the system out of planarity.
35
Lack of planarity is not a problem in [18]annulene (18 electrons; 4n +2 where n = 4), where there is sufficient room for the
central six hydrogen atoms to fit within the middle of the ring system.
Arenes: Electrophilic Aromatic Substitution

One of the most important reactions of arenes is electrophilic aromatic substitution, in which an electrophile reacts with the
ring, forming a new bond to a ring carbon with the loss of one hydrogen. In general, these reactions require a Lewis acid
catalyst, as shown below for the reaction of bromine with benzene, catalyzed by FeBr 3. The role of the FeBr 3 is to complex
the bromine to form a bromonium cation-like species (which is often simply referred to as Br+) which is the actual
electrophilic agent.
This electrophile first forms a loose complex with the cloud, which rearranges to a cationic sigma-complex, in which the
electrophile is directly bonded to a ring carbon. Since the ring is a conjugated system, the cationic charge which forms on the
adjacent carbon is delocalized over the ring, with partial positive charge developing on the carbons which are ortho- and
para- to the position where the electrophile bonded. Loss of H + from the sigma-complex regenerates the aromatic system
(with its associated stability), and gives bromobenzene and HBr as the final products.
36
Chlorination proceeds by a similar mechanism; for iodination, I 2/CuCl2 is typically utilized to generate the electrophilic I+
cation.
Aryl fluorides cannot be prepared by this direct method, but can be prepared using thallium trifluoroacetate to form an
intermediate aryl-thallium compound, which then reacts with fluoride anion to give the desired product.
Arenes can also be nitrated by a similar mechanism using a mixture of nitric and sulfuric acids to generate the electrophile
NO2+, which adds to the ring to form a sigma complex, and looses a proton to give the nitro compound.
37
Fuming sulfuric acid (H2SO4 saturated with SO3) to generate SO3H+, which is the electrophilic agent. The final product of the
reaction is the aryl sulfonic acid.
Perhaps the most notable (and useful) example of electrophilic aromatic substitution is the introduction of alkyl groups using
the Friedel-Crafts reaction. In this reaction, a Lewis acid complexes with an alkyl halide to give a species with electrophilic
character on the carbon of the alkyl halide. This then reacts by the standard mechanism to give an intermediate sigma-
complex, and the alkylated benzene as the final product.
There are several limitations of the Friedel-Crafts alkylation reaction, as shown below. Summarizing, only alkyl halides can
be utilized (not aryl- or vinyl halides); the ring must be activated, since the electrophile is generally less reactive than those
encountered previously; multiple substitutions are possible, and perhaps most important, since the carbon of the alkyl
halide has carbocation character, rearrangements often occur. In general this means that an alkyl halide such as 1-
bromopropane is not suitable in this reaction, since it would be prone to rearrange to the more stable isopropyl carbocation.
38
A derivative of the Friedel-Crafts alkylation is the Friedel-Crafts acylation reaction in which the arene is converted to an aryl
ketone. The electrophile in this reaction is an acylium ion-like species which is formed by reaction of an acid halide, or an
acid anhydride, with the Lewis acid. Unlike the alkylation reaction, rearrangements do not occur (the acylium cation is a very
stable, resonance-stabilized carbocation), although an activated ring is still required.
Orientation Effects in Electrophilic Aromatic Substitution

When electrophilic aromatic substitution occurs on a ring already bearing one or more substituent, the nature of that
substituent will impact both the rate of the reaction and the regiochemistry of the reaction (where on the ring the substitution
occurs). In the table shown below, activating substituents will react faster than benzene itself, and deactivating substituents
will react more slowly. Further, substituents are grouped into two categories; ortho- para- directing, and meta-directing.
A substituent is activating if it releases electron density into the ring either inductively, or through resonance (the electrophile
is, after all, looking for electrons; the more electron density, the faster the reaction). The orientation effect is seen by
considering the family of resonance forms which can be drawn for a substituent such as an alkoxy group; these clearly show
enhanced electron density localized ortho-and para- to the point of attachment.
39
Meta-directing substituents such as the nitro group can be seen to function by removing electron density from the ring ortho-
and para- to themselves, leaving only the meta-positions with sufficient electron density to support the electrophilic
(electron-seeking) reaction. Thus, meta-directing substituents don't really activate the meta-positions towards substitution,
they deactivate everywhere else.
Halogens are somewhat unique in that they deactivate inductively (and are therefore less reactive than benzene), but they
direct ortho-and para- since they enhance the electron density at these positions by resonance, as shown below.
When there are multiple substituents on a ring, the effects are generally either cumulative, or the most strongly activating
substituent ultimately directs the regiochemistry.
40
Arenes: Nucleophilic Aromatic Substitution
Arenes having strongly electron-withdrawing groups on the ring, and at least one potential leaving group (typically a
halogen) can undergo substitution to strong nucleophiles, as shown below for 1-fluoro-2,4-dinitrobenzene.
This substitution, however, cannot be occurring by a simple S N1 or SN2 mechanisms since the pathway for displacement in the
SN2 mechanism is blocked by the ring, and the S N1 mechanism would involve the generation of an unstable aryl cation on a
ring which is already extremely electron deficient.
The reaction, instead, involves an addition-elimination pathway, in which the nucleophile first adds to the ring at the carbon
bearing the leaving group to form an anionic complex. The electrons from the nucleophile are generally delocalized by the
other electron-withdrawing groups on the ring, and then are utilized to allow the halogen to leave as an anion, restoring the
stable aromatic system.
41
Nitro-groups are especially good at promoting this type of reaction, since the intermediate anionic charge can be delocalized
onto the oxygens of the nitro group as relatively stable oxyanions.
Arenes: Reactions of Aryl Side-Chains

Arenes having an alkyl side-chain with at least one benzylic hydrogen will undergo oxidation in the presence of neutral
MnO4- anion to give the corresponding benzoic acid. Note that in the example given below, the same product (benzoic acid) is
produced by all three reactions, with the remaining carbons appearing as secondary oxidation products. As with all reactions
involving MnO4-, the reaction involves radical intermediates and side reactions are common.
Alkyl-substituted arylsulfonic acids undergo a somewhat brutal reaction know as "alkali fusion" in which the sulfonic acid
residue is replaced by a hydroxyl group, yielding a substituted phenol. Because of the extreme reaction conditions, the
reaction is limited to simple compounds, but is a useful pathway to forming phenols.
42
Since benzyl radicals are quite stable (being resonance-stabilized by the adjacent ring), free radical bromination occurs quite
rapidly on alkyl benzenes having at least one benzylic hydrogen. The reaction conditions employed often utilize NBS (N-
bromosuccinimide) in CCl4 in the presence of a "radical initiator" to generate the bromine radical.
Since arenes are resistant to catalytic reduction, alkene side-chains can be specifically reduced to the alkane without reducing
the ring. If you want to reduce the ring, high temperatures and pressure are required when standard catalysts are utilized (Pt
or Pd), although Rh will catalyze the reduction under very mild conditions.
Catalytic reduction will also reduce aryl nitro groups to the corresponding amine (or, specific reduction can be accomplished
using acidic SnCl2). Likewise, aryl ketones are smoothly reduced catalytically to give the corresponding alkane. This latter
reaction is quite often useful since an alkyl chain which would be prone to rearrangement in a Friedel-Crafts
alkylation can be introduced using an acylation, and then simple reduced to the alkane.
43
Alcohols, Phenols and Ethers
Alcohols & Ethers: Nomenclature

Simple alcohols are named as derivatives of the parent alkane, using the suffix -ol, using the following simple rules:
1. Select the longest continuous carbon chain, containing the hydroxyl group, and derive the parent name by replacing
the -e ending with -ol.
2. Number the carbon chain, beginning at the end nearest to the hydroxyl group.
Some Examples:
44
Alcohols are also known by a wide variety of common names, some of which are given below:
Simple ethers are named either by identifying the two organic residues and adding the word ether, or, if other functionality is
present, the ether residue is named as an alkoxy substituent, as shown below:
Some Examples:
45
Reactions that Yield Alcohols
Hydration of Alkenes: Simple acid-catalyzed hydration of alkenes is a stepwise reaction involving a carbocation
intermediate. Rearrangements will often occur and hydroxide anion will bond to the most stable carbocation center in the
molecule (Markovnikov's Rule).
Oxymercuration of Alkenes: Oxymercuration of alkenes is a stepwise reaction involving a bridged mercurinium ion
intermediate. In unsymmetrical alkenes, the alkene carbon which would form the most stable carbocation will bear more of
the positive charge and will be attacked by hydroxide anion (or water) to give the addition intermediate; rearrangements do
not occur, but the orientation follows Markovnikov's Rule. In a second step, BH 4- is used to remove the mercury and give the
final product.
46
Hydroboration of an Alkene, with Oxidative Work-up: Reaction of an alkene with BH 3 results in the syn-addition of the
boron and a hydrogen across the double bond. Rearrangements do not occur and the hydrogen will bond to the carbon of the
alkene which would form the most stable carbocation center (overall anti-Markovnikov's addition). The driving force for the
regiochemistry may actually be more steric than electronic, but viewing the reaction as a concerted, but polar transition state,
easily rationalizes the observed product distribution.
Formation of 1,2-Diols from Alkenes: Reaction of an alkene with MnO 4- or OsO4 results in the formation of a cis-1,2-diol.
The reaction involves the formation of an intermediate cyclic ester, which decomposes to give the diol. For OsO 4, reaction
with HSO3- is necessary to decompose the intermediate ester and form the final product.
Preparation of Alcohols by Reduction of Aldehydes and Ketones: Reduction of simple aldehydes and ketones with BH4-
yields the corresponding alcohol directly. The reaction works well for simple compounds, but reaction of BH 4- with
unsaturated aldehydes and ketones can result in significant reduction of the double bond.
A much more powerful reductant is LiAlH4, which will reduce aldehydes, ketones, esters, carboxylic acids and nitriles. Some
sample reactions are shown below:
47
As seen in the first example, the reduction of carboxylate esters results in the addition of two moles of hydride to the
carbonyl carbon, with loss of the alcohol portion of the ester, forming the corresponding primary alcohol.
The Grignard Reaction
Preparation of Alcohols by Addition of Grignard Reagents to Carbonyl Compounds

The reaction of an alkyl, aryl or vinyl halide with magnesium metal in ether solvent, produces an organometallic complex of
uncertain structure, but which behaves as if it has the structure R-Mg-X and is commonly referred to as a Grignard Reagent.
The "R" group in this complex (alkyl, aryl or vinyl), acts as if it was a stabilized carbanion and Grignard reagents react with
water and other compounds containing acidic hydrogens to give hydrocarbons (just as would be expected for a well-behaved,
highly basic carbanion). In the absence of acidic hydrogens, the Grignard reagent can function as a powerful nucleophile, and
is most often used in addition reactions involving carbonyl compounds, as shown above. The product of these addition
reactions is typically a secondary or tertiary alcohol (primary alcohols can be formed by reaction with formaldehyde), as
shown in the examples below; in these the carbonyl and halide portions of the molecules have been colored blue and red,
respectively, to assist in understanding the component parts of the final products.
48
Carboxylate esters also react with Grignard reagents, undergoing the addition of two moles of reagent to give the final
product. The reason for this is clearly seen in the example below, where the product of the first mole of addition is the simple
carbonyl compound, which rapidly adds a second mole of reagent.
Strained ethers also react with Grignard reagents to give alcohols, as shown below for reaction with epoxides.
Ethers in four-membered rings can also undergo attack, although the reaction of ethers with Grignard reagent is commonly
reserved for epoxides. The regiochemistry of the reaction with epoxides is generally dictated by steric factors.
49
Reactions of Alcohols
Conversion to Alkyl Chlorides by Reaction with HCl: Tertiary alcohols, or alcohols which can lose the hydroxyl group to
form a stable carbocation, can undergo an S N1 substitution reaction with HCl gas dissolved in ether to give the corresponding
alkyl chloride. Again, the reaction is limited to alcohols that can from stable carbocations.
Conversion to Alkyl Bromides by Reaction with PBr 3: Primary and secondary alcohols react with PBr3 to form an
intermediate phosphite ester which undergoes SN2 attack by bromide anion to yield the alkyl bromide with inversion of
configuration (the stereochemical inversion is simply a result of the SN2 displacement).
Conversion to Alkyl Chlorides by Reaction with SOCl 2: Primary and secondary alcohols react with SOCl 2 in polar
solvents (i.e., pyridine) to form an intermediate sulfite ester which undergoes S N2 attack by chloride anion to yield the alkyl
chloride with inversion of configuration (the stereochemical inversion is simply a result of the S N2 displacement). If the
reaction is performed in a non-polar solvent such as benzene, an unusual S Ni mechanism occurs involving frontside attack,
and yielding retention of stereochemistry. This reaction is unusual, but is often useful if you desire to control the
stereochemical course of a synthesis.
50
Dehydration of Tertiary Alcohols: Tertiary alcohols, or alcohols which can lose the hydroxyl group to form a stable
carbocation, can undergo an acid-catalyzed E1 elimination reaction to form the corresponding alkene. Again, the reaction is
limited to alcohols that can from stable carbocations.
Dehydration of Secondary and Tertiary Alcohols with POCl 3: Secondary and tertiary alcohols react with POCl 3 to form a
dichlorophosphate ester, which undergos an E2 elimination reaction to form the corresponding alkene. Since an E2
elimination is occurring, the hydrogen abstracted must be anti- and coplanar with the oxygen on the leaving group
(antarafacial).
Oxidation of Alcohols with Pyridinium Chlorochromate: Primary and secondary alcohols are smoothly oxidized by
pyridinium chlorochromate (PCC) in CH2Cl2 to form aldehydes and ketones, respectively. The PCC oxidation of primary
alcohols to give aldehydes is a very useful reaction, since aldehydes are difficult to prepare and are easily over-oxidized to
the carboxylic acid.
51
Oxidation of Alcohols with "Jones Reagent": Primary and secondary alcohols are oxidized by CrO3/H2SO4 (Jones Reagent)
to form carboxylic acids and ketones, respectively; sodium dichromate in acetic acid (Na 2Cr2O7) can also be used.
Conversion to Silyl Ethers: Alcohols react with chlorotrimethylsilane to form trimethylsilyl ethers which are stable to many
reactions which occur in aprotic medium, but can be readily cleaved by reaction with aqueous acid, regenerating the alcohol.
This reaction is often utilized to "protect" an alcohol during a synthesis, such as that shown below (in the synthesis shown,
the Grignard reagent would react with the acidic proton on the alcohol, destroying the reagent).
52
Ethers, Synthesis & Reactions
Synthesis by SN2 Displacement Reactions: Unhindered primary and secondary alkyl halides react with simple (unhindered)
alkoxides by an SN2 mechanism yielding ethers (the Williamson Ether Synthesis).
Synthesis
Oxymercuration of Alkenes in the Presence of Alcohols: Oxymercuration of alkenes is a stepwise reaction involving a
bridged mercurinium ion intermediate. In unsymmetrical alkenes, the alkene carbon which would form the most stable
carbocation will bear more of the positive charge and, in alcohols, will be attacked by alkoxide anion (or the alcohol) to give
the addition intermediate; rearrangements do not occur, but the orientation follows Markovnikov's Rule. In a second step,
BH4- is used to remove the mercury and give the final product.
Formation of Epoxides by Oxidation of Alkenes: Alkenes undergo partial oxidation with peracids to form epoxides. A
stable and useful reagent for this reaction is the magnesium salt of monoperoxyphthalate (MMPP).
53
Formation of Epoxides by an Internal S N2 Reaction in Halohydrins: Halohydrins (prepared by the addition of HOX to an
alkene) undergo an internal SN2 reaction in the presence of strong base (NaOH) to give epoxides.
Reactions
Cleavage of Ethers with HI: Ethers undergo cleavage in the presence of aqueous HI to give the corresponding alkyl iodide.
Attack will be at the least hindered carbon and E1 reactions, with carbocation intermediates, are common with ethers with
groups which can form stable carbocations.
Ring-Opening Reactions of Epoxides: The three-membered ring of epoxides is highly strained and undergoes ring-opening
reactions with a variety of nucleophiles, as shown below.
54
For reactions involving acid catalysis, the first step involves protonation of the ether oxygen to make it a better leaving group,
followed by nucleophilic attack.
More examples:
Reactions of Phenols
Phenols, like simple alcohols, will form an anion which will undergo an S N2 reaction with alkyl halides (or alkyl groups with
"good leaving groups") to give ethers. They will also react with activated carbonyl compounds to undergo acyl transfer
reactions; thus aryl esters are readily formed by the reaction of phenols with acid halides or acid anhydrides. As with aryl
amines, the ring of phenols is electron-rich and will rapidly react with Br2 to give a tri-substituted product.
55
The last reaction shown above is a specific and unusual reaction of phenols, that is the direct reaction with CO 2 to give
carboxylation at the ortho-postion. This reaction is called the Kolbe-Schmitt carboxylation, and is important since the
product is salicylic acid, which is widely used in pharmaceuticals.
Another reaction which is highly specific for phenols is oxidation with Fremy's salt: potassium nitrosodisulfonate, to give the
para-quinone as product.
56
Aldehydes and Ketones
Aldehydes & Ketones: Nomenclature

Simple aldehydes and ketones are named using the standard rules of nomenclature which we have used in the past with the
following specific changes:
1. Aldehydes are named by replacing the terminal -e of the parent alkane with the suffix -al; the suffix for ketones is -
one.
2. The parent chain selected must contain the carbonyl group.

3. Number the carbon chain, beginning at the end nearest to the carbonyl group.
5. When an aldehyde is a substituent on a ring, it is referred to as a -carbaldehyde group.
6. When the -COR group becomes a substituent on another chain, it is referred to as an acyl group and the name is
formed using the suffix -yl.
57
7. When the carbonyl group becomes a substituent on another chain, it is referred to as an oxo group.
Some Examples:
Reactions that Yield Aldehydes & Ketones

Oxidation of Alcohols with Pyridinium Chlorochromate: Primary and secondary alcohols are smoothly oxidized by
pyridinium chlorochromate (PCC) in CH2Cl2 to form aldehydes and ketones, respectively. The PCC oxidation of primary
alcohols to give aldehydes is a very useful reaction, since aldehydes are difficult to prepare and are easily over-oxidized to
the carboxylic acid.
Oxidation of Alcohols with "Jones Reagent": Primary and secondary alcohols are oxidized by CrO3/H2SO4 (Jones Reagent)
to form carboxylic acids and ketones, respectively; sodium dichromate in acetic acid (Na 2Cr2O7) can also be used.
58
Ozonolysis of Alkenes: Simple alkenes are are oxidized by O 3 to form an intermediate ozonide, which undergoes dissolving
metal reduction with Zn/H3O+ to produce aldehydes and ketones.
Oxidation of Alkenes: Simple alkenes are are oxidized by MnO4- to produce aldehydes and ketones. Terminal alkenes yield
CO2, while alkene carbons bearing one hydrogen form the corresponding carboxylic acid.
Hydration of Alkynes: Acid-catalyzed hydration of alkynes in the presence of Hg +2 yields an intermediate enol, which
rapidly equilibrates with the corresponding carbonyl compound. The regiochemistry of the reaction is "Markovnikov"; that is,
hydroxide anion will bond to the most stable potential carbocation center of the alkyne.
59
Hydroboration of an Alkyne, with Oxidative Work-up: Reaction of an alkyne with BH3 results in the syn-addition of the
boron and a hydrogen across the triple bond. Rearrangements do not occur and the hydrogen will bond to the carbon of the
alkyne which would form the most stable carbocation center (overall anti-Markovnikov's addition). The driving force for the
regiochemistry may actually be more steric than electronic, but viewing the reaction as a concerted, but polar transition state,
easily rationalizes the observed product distribution. On oxidative work-up, the borane is converted to the enol, which rapidly
equilibrates with the corresponding carbonyl compound.
Friedel-Crafts Acylation: Arenes react with acid halides and acid anhydrides in the presence of AlCl 3 to form aryl ketones.
This is an example of electrophilic aromatic substitution, and the reaction does not proceed well on rings which are strongly
deactivated.
60
Reactions of Aldehydes & Ketones
The Grignard Reaction: The reaction of an alkyl, aryl or vinyl halide with magnesium metal in ether solvent, produces an
organometallic complex of uncertain structure, but which behaves as if it has the structure R-Mg-X and is commonly referred
to as a Grignard Reagent.
The "R" group in this complex (alkyl, aryl or vinyl), acts as if it was a stabilized carbanion and Grignard reagents react with
water and other compounds containing acidic hydrogens to give hydrocarbons (just as would be expected for a well-behaved,
highly basic carbanion). In the absence of acidic hydrogens, the Grignard reagent can function as a powerful nucleophile, and
is most often used in addition reactions involving carbonyl compounds, as shown above. The product of these addition
reactions is typically a secondary or tertiary alcohol (primary alcohols can be formed by reaction with formaldehyde), as
shown in the examples below; in these the carbonyl and halide portions of the molecules have been colored blue and red,
respectively, to assist in understanding the component parts of the final products.
Hydration of Aldehydes & Ketones: The hydration of carbonyl compounds is an equilibrium process and the extent of that
equilibrium generally parallels the reactivity of the parent aldehyde or ketone towards nucleophilic substitution; aldehydes
are more reactive than ketones and are more highly hydrated at equilibrium.
61
Formation of Cyanohydrins: The reaction of carbonyl compounds with HCN is an equilibrium process and, again, the
extent of that equilibrium generally parallels the reactivity of the parent aldehyde or ketone towards nucleophilic substitution.
Reaction with Amines: The reaction of carbonyl compounds with amines involves the formation of an intermediate
carbinolamine which undergoes dehydration to form an immonium cation which can loose a proton to form the neutral
imine.
Some examples of common imine-forming reactions are given below:
Imines formed from secondary amines can loose a proton from the carbon to form an enamine. Because of resonance,
enamines maintain a partial carbanion character on the carbon and can be utilized as nucleophiles, as will be discussed in
the section on "alpha alkylations".
62
Ketal and Acetal Formation: Ketones and aldehydes react with excess alcohol in the presence of acid to give ketals and
acetals, respectively. The mechanism of acetal formation involves equilibrium protonation, attack by alcohol, and then loss
of a proton to give the neutral hemiacetal (or hemiketal). The hemiacetal undergoes protonation and loss of water to give an
oxocarbonium ion, which undergoes attack by another mole of alcohol and loss of a proton to give the final product; note that
acetal (or ketal) formation is an equilibrium process.
Some examples of acetal and ketal formation are given below:
The Wittig Reaction: Ketones and aldehydes react with phosphorus ylides to form alkenes. Phosphorus ylides are prepared
by an SN2 reaction between an alkyl halide and triphenylphosphine, followed by deprotonation by a strong base such as n-
butyllithium. The mechanism of the Wittig reaction involves nucleophilic addition to give an intermediate betaine, which
decomposes to give the alkene and triphenylphosphine oxide. The Wittig reaction works well to prepare mono- di- and tri-
substituted alkenes; tetra-substituted alkenes cannot be prepared by this method.
63
Oxidation & Reduction of Aldehydes and Ketones
Reduction of simple aldehydes and ketones

Preparation of Alcohols by Reduction of Aldehydes and Ketones:
with BH yields the corresponding alcohol directly. The reaction works well for simple compounds, but
4
-
reaction of BH with unsaturated aldehydes and ketones can result in significant reduction of the
4
-
double bond.
A much more powerful reductant is LiAlH4, which will reduce aldehydes, ketones, esters, carboxylic acids and nitriles. Some
sample reactions are shown below:
As seen in the first example, the reduction of carboxylate esters results in the addition of two moles of hydride to the
carbonyl carbon, with loss of the alcohol portion of the ester, forming the corresponding primary alcohol.
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Although the reduction of esters with LiAlH4 proceeds to produce the alcohol, reduction of carboxylate esters by
diisobutylaluminum hydride (DIBAH) stops at the aldehyde.
Wolff-Kishner Reduction: The imine formed from an aldehyde or ketone on reaction with hydrazine (NH 2NH2) is unstable
in base, and undergoes loss of N2 to give the corresponding hydrocarbon.
Clemmensen Reduction: Carbonyl compounds can also be reduced by the Clemmensen reduction using zinc-mercury
amalgam in the presence of acid; the mechanism most likely involves free radicals.
65
The Formation of Thioketal and Thioacetals: Ketones and aldehydes react with excess thiol in the presence of acid to give
thioketals and thioacetals, respectively. These compounds are smoothly reduced by Raney-Nickel to give the corresponding
hydrocarbons.
Oxidation of Aldehydes by Silver Oxide: Reaction of simple aldehydes with aqueous Ag 2O in the presence of NH 3 yields
the corresponding carboxylic acid and metallic silver. The silver is generally deposited in a thin metallic layer which forms a
reflective "mirror" on the inside surface of the reaction vessel. The formation of this mirror forms the basis of a qualitative
test for aldehydes, called the Tollens Test.
Oxidation of Aldehydes to form Carboxylic Acids: Reaction of simple aldehydes with acidic MnO 4-, or CrO3/H2SO4 yields
the corresponding carboxylic acid. Aldehydes oxidize very easily and it is often difficult to prevent oxidation, even by
atmospheric oxygen.
Oxidation of Ketones: Ketones are more resistant to oxidation, but can be cleaved with acidic MnO 4- to yield carboxylic
acids.
66
Reactions of Aldehydes & Ketones; Conjugate Additions
Conjugated ketones and aldehydes can undergo a reaction which is analogous to the 1,4-addition reaction of dienes, in which
a nucleophile adds to the terminal carbon of the double bond. As in dienes, resonance throughout the conjugated system
places cationic character on both carbons #1 and 3.
Addition of Amines: Amines add to conjugated ketones and aldehydes to give the conjugate addition product, almost
exclusively.
Addition of HCN: HCN, or preferably (CH3CH2)2AlCN, will also add to conjugated ketones and aldehydes to exclusively
give the conjugate addition product.
67
Addition of Alkyl and Aryl Groups: Alkyl, aryl and vinyl groups can be added to conjugated ketones using the appropriate
dialkylcopperlithium reagent.
The utility of conjugate addition reactions in organic synthesis is demonstrated by the reaction sequence shown below:
68
Carboxylic Acids
Nomenclature of Carboxylic Acids

Simple carboxylic acids are named as derivatives of the parent alkane, using the suffix -oic acid
1. Select the longest continuous carbon chain, containing the carboxylic acid group, and derive the parent name by
replacing the -e ending with -oic acid.
2. Number the carbon chain, beginning at the end nearest to the carboxylic acid group.
4. Carboxylic acid substituents attached to rings are named using the suffix -carboxylic acid.
In the first example, the parent chain is a pentane and the carboxylic acid group is assigned as carbon #1. On the pentane
parent, there is an ethyl group in position #2; hence the name, 2-ethylpentanoic acid.
In the second example, there are two potential four-carbon chains; in this case, the chain with the most substituents is
selected as parent, (a butanoic acid). Attached to the butanoic acid at carbon #2 is an ethyl group and at carbon #3, a
bromine; hence the name 3-bromo-2-ethylbutanoic acid.
In the third example, the carboxylic acid is attached to a cycloalkene ring and will therefore be named as a "carboxylic acid"
substituent (rule #4). The parent ring is a cyclohexene ; letting the carboxylic acid be carbon #1, the name is 2-
cyclohexenecarboxylic acid.
In the last example, the name is based on benzoic acid as the parent. In this case, we simply number the substituents to give
the lowest number sequence at the first point of difference and arrange alphabetically; 5-bromo-2-methylbenzoic acid.
Reactions which Yield Carboxylic Acids

Oxidation of Aromatic Side-Chains with Neutral Permaganate
69
Warm, neutral permaganate anion will oxidize aromatic side-chains which contain at least one benzylic hydrogen to the
corresponding carboxylic acid.
Primary alcohols can be oxidized smoothly to the corresponding carboxylic acid with either CrO 3/H2SO4 or sodium
dichromate.
Acidic MnO4- will oxidize an alkene bearing at least one alkyl or aryl substituent to the corresponding carboxylic acid.
Terminal alkenes are converted to CO2 under these conditions.
Aldehydes are smoothly oxidized to the corresponding carboxylic acid with either CrO3/H2SO4 or sodium dichromate.
70
Aldehydes (but not ketones) are oxidized by Ag 2O in aqueous ammonia to give the carboxylic acid and metallic silver. This is
used as a qualitative test for aldehydes since the silver metal is deposited in a thin film, forming a "silver mirror" (the Tollens
test).
Acidic MnO4- will oxidize a ketone to the corresponding carboxylic acid, in this case, splitting the ring. The reaction is slower
than the oxidation of alkenes, allowing disubstituted alkene carbons to be oxidized to the ketone, without significant over-
oxidation.
Nitriles can be hydrolyzed to the corresponding carboxylic acids. Typically, vigorous conditions are required (heat and
concentrated acid).
Grignard reagents react with CO2 to yield carboxylic acids. This is an important method for the preparation of carboxylic
acids and yields are generally good.
Reactions of Carboxylic Acids

71
Carboxylic acids can be reduced to primary alcohols with LiAlH4 or with BH3 followed by work-up with aqueous acid. In the
reduction with LiAlH4, an intermediate aldehyde is formed, which is rapidly reduced to give the primary alcohol.
Heavy metal salts of carboxylic acids undergo decarboxylation on heating in organic solvents. In the presence of Br 2, the
radical intermediate is trapped as an alkyl bromide (the Hunsdiecker reaction).
Carboxylic acids can be converted into acid halides by reaction with SOCl2, phosgene, or PBr3.
72
Carboxylic acids can be converted into esters by reaction with the corresponding alcohol in the presence of an acid catalyst
(Fischer esterification), by alkylation of the carboxylate anion with an alkyl halide in an S N2 reaction, or by reaction with
diazomethane (methyl esters only).
Acyl Derivatives (Carboxylic Acid Derivatives)
Nomenclature of Carboxylic Acid Derivatives

The following page contains a detailed description of the IUPAC rules for the naming of common carboxylic acid
derivatives; a summary of these rules is given in the figure below.
Simple carboxylic acids are named as derivatives of the parent alkane, using the suffix -oic acid
replacing the -e ending with -oic acid.
2. Number the carbon chain, beginning at the end nearest to the carboxylic acid group.
4. Carboxylic acid substituents attached to rings are named using the suffix -carboxylic acid.
73
In the first example, the parent chain is a pentane and the carboxylic acid group is assigned as carbon #1. On the pentane
parent, there is an ethyl group in position #2; hence the name, 2-ethylpentanoic acid.
selected as parent, (a butanoic acid). Attached to the butanoic acid at carbon #2 is an ethyl group and at carbon #3, a
bromine; hence the name 3-bromo-2-ethylbutanoic acid.
In the third example, the carboxylic acid is attached to a cycloalkene ring and will therefore be named as a "carboxylic acid"
substituent (rule #4). The parent ring is a cyclohexene ; letting the carboxylic acid be carbon #1, the name is 2-
cyclohexenecarboxylic acid.
the lowest number sequence at the first point of difference and arrange alphabetically; 5-bromo-2-methylbenzoic acid.
Simple acid halides are named by identifying the acyl group, using the suffix -oyl followed by the halogen.
1. Select the longest continuous carbon chain, containing the acyl group, and derive the parent name by replacing the -
e ending with -oyl, then append the halogen.
2. Number the carbon chain, beginning at the end nearest to the acyl group.
4. Acid halide substituents attached to rings are named using the suffix -carbonyl.
74
In the first example, the parent chain is a pentane and the acyl group is assigned as carbon #1. On the pentane parent, there is
an ethyl group in position #2; hence the name, 2-ethylpentanoyl chloride.
selected as parent, (a butanoyl bromide). Attached to the chain at carbon #2 is an ethyl group and at carbon #3, a bromine;
hence the name 3-bromo-2-ethylbutanoyl bromide.
In the third example, the acyl group is attached to a cycloalkene ring and will therefore be named as a "carbonyl chloride"
substituent (rule #4). The parent ring is a cyclohexene ; letting the acyl group be carbon #1, the name is 2-
cyclohexenecarbonyl chloride.
the lowest number sequence at the first point of difference and arrange alphabetically; 5-bromo-2-methylbenzoyl fluoride.
Simple acid anhydrides are named by replacing the ending "acid" with "anhydride".
replacing the -e ending with -oic anhydride.
In the first example, the parent chains are both pentane; hence the name, pentanoic anhydride (also as bis-pentanoic
anhydride).
In the second example, there are two parent chains; ethanoic acid and butanoic acid; hence the name butanoic ethanoic
anhydride (acetic can be used in place of ethanoic).
In the third example, the name is based on benzoic acid as the parent, and the name is simply benzoic anhydride.
In the last example, the name is based on phthalic acid and the name is simply phthalic anhydride.
Simple amides are named by replacing the ending -oic acid with -amide .
e ending with -amide.
4. Acid halide substituents attached to rings are named using the suffix -carboxamide.
5. If the nitrogen atom is further substituted, the substituents are preceded by N- to indicate that they are attached to the
nitrogen.
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In the first example, the parent chain is a pentane and the acyl group is assigned as carbon #1. On the pentane parent, there is
an ethyl group in position #2; hence the name, 2-ethylpentanamide.
selected as parent, (a butane). Attached to the chain at carbon #2 is an ethyl group and at carbon #3, a bromine; hence the
name 3-bromo-2-ethylbutanamide.
In the third example, the acyl group is attached to a cycloalkene ring and will therefore be named as a "carboxamide"
cyclohexenecarboxamide.
In the last example, the name is based on benzoic acid as the parent and the nitrogen has a methyl substituent. In this case,
we simply number the substituents to give the lowest number sequence at the first point of difference and arrange
alphabetically; N-methyl-5-bromo-2-methylbenzamide.
Simple carboxylate esters are named as derivatives of the carboxylic acid, by changing the suffix -oic acid to -oate, and
naming the alcohol portion first.
e ending with -oate, then append the the alcohol to the front of the name.
4. Acid halide substituents attached to rings are named using the suffix -carboxylate.
76
In the first example, the alcohol is methanol the parent chain is a pentane and the acyl group is assigned as carbon #1. On
the pentane parent, there is an ethyl group in position #2; hence the name, methyl 2-ethylpentanoate.
In the second example, the alcohol is ethanol and there are two potential four-carbon chains; in this case, the chain with the
most substituents is selected as parent, (a butanoyl bromide). Attached to the chain at carbon #2 is an ethyl group and at
carbon #3, a bromine; hence the name ethyl 3-bromo-2-ethylbutanoate.
In the third example, the alcohol is cyclopentanol and the acyl group is attached to a cycloalkene ring and will therefore be
named as a "carboxylate" substituent (rule #4). The parent ring is a cyclohexene ; letting the acyl group be carbon #1, the
name is cyclopentyl 2-cyclohexenecarboxylate.
In the last example, the alcohol is methanol and the name is based on benzoic acid as the parent. In this case, we simply
number the substituents to give the lowest number sequence at the first point of difference and arrange alphabetically; methyl
5-bromo-2-methylbenzoate.
Simple nitriles are named as derivatives of the parent alkane, using the suffix -nitrile to -oate, and naming the alcohol
portion first.
1. Select the longest continuous carbon chain, containing the nitrile, and derive the parent name by appending -nitrile.
2. Number the carbon chain, beginning at the end nearest to the nitrile group.
4. Acid halide substituents attached to rings are named using the suffix -carbonitrile.
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In the first example, the parent chain is a pentane and the nitrile group is assigned as carbon #1. On the pentane parent, there
is an ethyl group in position #2; hence the name, 2-ethylpentanenitrile.
selected as parent, (a butanenitrile). Attached to the chain at carbon #2 is an ethyl group and at carbon #3, a bromine;
hence the name 3-bromo-2-ethylbutanenitrile.
In the third example the nitrile group is attached to a cycloalkene ring and will therefore be named as a "carbonitrile"
cyclohexenecarbonitrile.
In the last example the name is based on benzonitrile as the parent. In this case, we simply number the substituents to give
the lowest number sequence at the first point of difference and arrange alphabetically; <B5-BROMO-2-
METHYLBENZONITRILE< B>.
The Partitioning of Tetrahedral Intermediates

The attack of a nucleophile on an acyl derivative results in the formation of a transient tetrahedral intermediate. This
intermediate partitions, that is, breaks down, by a series of parallel pathways to generate a series of products which is
governed by the exact nature of the intermediate and the individual microscopic rate constants for each potential pathway.
For tetrahedral intermediates formed from simply acyl derivatives, it is possible to apply a simple set of rules to determine
which group around the tetrahedral center is the "best leaving group", and hence, what will be the predominate product of a
given reaction.
In general, for tetrahedral intermediates involving anionic leaving groups, you can assume that the best leaving group will
be that group which has the strongest conjugate acid.
For example, consider the intermediate shown below. The potential leaving groups are methoxide and phenoxide. The
conjugate acids of methoxide and phenolate anions are methanol, pKa=16, and phenol, pKa=9 (approximate pKavalues). The
strongest acid is phenol, and the major product formed will be ethyl acetate.
78
Another example; the tetrahedral intermediate shown below has two potential leaving groups, chloride and phenoxide. The
strongest conjugate acid is HCl, hence chloride anion is most likely to leave and the major product will be phenyl acetate.
Again, the process is simply to examine the potential leaving groups, determine which has the strongest conjugate acid (the
lower pKa), reform the carbonyl, allowing that group to leave and draw the final product.
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Reactions of Carboxylic Acid Derivatives
Acid Halides
Acid halides are the most reactive acyl derivatives, and can be readily converted into carboxylic acids, esters and amides, by
simple reaction with the appropriate nucleophile. The reaction involves an addition-elimination mechanism, as shown below:
Reaction of acid halides with Grignard reagents, or reduction with LiAlH 4, leads to the incorporation of two moles of
Grignard (or hydride), in a mechanism which involves an intermediate aldehyde or ketone, as shown below for hydride
reduction.
When a bulky reducing agent, such as lithium tri-tert-butoxylaluminum hydride is utilized, the reduction or acyl halides can
be stopped at the intermediate aldehyde.
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Partial alkylation can be achieved with acyl halides by reaction with a dialkylcopper lithium reagent, at low temperatures.
This reaction is also useful for unsaturated aldehydes and ketones since conjugate addition of the alkyl group does not
occur at the low temperatures utilized.
Acid Anhydrides
Acid halides are the next most reactive acyl derivatives, and can be readily converted into carboxylic acids, esters and
amides, by simple reaction with the appropriate nucleophile. The reaction involves an addition-elimination mechanism, as
shown below:
As with acid halides, reduction of anhydrides with LiAlH 4 results in the addition of two moles of hydride, forming the
primary alcohol.
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Carboxylic Esters
Carboxylate esters can be readily converted into carboxylic acids and amides, by simple reaction with the appropriate
nucleophile. The reaction involves an addition-elimination mechanism, as shown below:
Reaction of esters with Grignard reagents, or reduction with LiAlH 4, leads to the incorporation of two moles of Grignard (or
hydride), in a mechanism which involves an intermediate aldehyde or ketone, as shown below for hydride reduction.
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Amides
Amides are relatively unreactive in acyl transfer reactions, largely because the electrons from the adjacent nitrogen
participate in resonance delocalization with the adjacent carbonyl, making the carbonyl carbon significantly less
electropositive.
Amides undergo acid-catalyzed hydrolysis to give carboxylic acids by the addition-elimination mechanism shown below:
Unsubstituted amides also undergo dehydration in the presence of SOCl2 to give the corresponding nitrile.
Nitriles
83
Nitriles can be hydrolyzed carboxylic acids, converted into ketones by reaction with Grignard reagents, reduced to primary
amines with LiAlH4 and partially reduced to aldehydes using DIBAH (diisobutylaluminum hydride). The reaction with
Grignard reagent is typical of these latter reactions and involves nucleophilic attack on the nitrile carbon to give an anionic
intermediate which is resistant to further attack, and undergoes hydrolysis to give a ketone, as shown below.
84
Carbonyl a-Substitution
Carbonyl -Substitution Reactions

Carbonyl compounds exist in equilibrium with a very small amount of a structural isomer, termed an enol. An enol is formed
by abstraction of a proton from the carbon, delocalization of the electrons onto the carbonyl oxygen, and finally,
protonation of the oxygen to give an alkene bonded to an alcohol (an enol!). It is important to note that this is a true
equilibrium and the carbonyl compound and its enol are distinct different chemical species, not resonance forms. Since
both proton abstraction and donation are required in the isomerization, keto-enol isomerization is catalyzed by both acids and
bases.
In spite of their low equilibrium concentrations, enols and enolate anions are useful in organic chemistry because they can be
used as nucleophiles to attack electrophilic centers such as Br2, alkyl halides, and other carbonyl carbons.
Bromination of an carbon is accomplished by reacting the carbonyl compound with bromine in an acidic solution (or in
acetic acid as solvent). Under these conditions, the carbanion character of the enol attacks Br2 to form the bromo
carbonyl compound, as shown below.
85
Chlorine can be introduced into the position conveniently using Cl2 in aqueous HCl.
The same general rules apply regarding enol stability as for alkenes, that is, the more highly substituted enol is favored,
unless it is crowded sterically.
The halo ketones and aldehydes which are formed can undergo an E2 elimination reaction in the presence of base to give
the unsaturated ketone or aldehyde; pyridine is commonly used as a base for this purpose.
Unsaturated ketones can also be prepared using an intermediate organo-selenium compound. Reaction of an enolizable
carbon with LDA (lithium diisopropylamide; a very strong base prepared from diisopropylamine and butyllithium) generates
the stable enolate anion as the lithium salt. This reacts with benzeneselenyl bromide to give the selenium intermediate,
which is not isolated, but is oxidized with H2O2 to a powerful leaving group which eliminates to form the unsaturated
ketone. The real beauty of this reaction is that it is useful for nitriles and esters, as well as ketones.
86
Direct bromination in acetic acid is limited to ketones and aldehydes, but bromo acids can be prepared using the Hell-
Volhard-Zelinskii reaction. This reaction involves the conversion of the acid to the intermediate acid bromide, enolization,
bromination to give the bromo acid bromide. The final step is work-up with water, which hydrolyzes the acid bromide to
the acid, yielding the bromo acid as the final product. An interesting twist on this reaction is to work up the product in
alcohol; this variation yields the corresponding bromo ester.
In another variation on the halogenation reaction, reaction of a methyl ketone or acetaldehyde (the only methyl aldehyde)
with I2 in the presence of hydroxide anion generates the triiodo-ketone. Attack by hydroxide anion on this forms the
corresponding carboxylic acid and iodoform, a yellow compound which is insoluble in the aqueous base. A precipitate of
iodoform is a standard qualitative test for the presence of a methyl ketone.
87
The Malonic Ester Synthesis
One of the most useful reactions involving enolates is their alkylation, using an alkyl halide as electrophile. These reactions
are best performed using compounds with acidic hydrogens, typically those adjacent to two carbonyls or nitrile groups.
Esters of malonic acid (propanedioic acid) are commonly used for these reactions and the reactions are generally referred to
as the malonic ester synthesis. The hydrogens of diethyl malonate have a pKa of about 10, and in the presence of ethoxide
in ethanol, it is completely converted to the enolate anion.
If an alkyl halide is present, the enolate anion can undergo an SN2 reaction to give a mono-alkylmalonic ester.
Acid hydrolysis of the diester generates the diacid, which is a carbonyl carboxylic acid. These are unstable, and undergo
decarboxylation in the acidic solution to give the acid-enol, which isomerizes to give the final product, a simple carboxylic
acid. You should note, however, that two carbons of the malonic ester have been added to the carbon skeleton of the
alkyl halide which was used in the first step. Thus, using the malonic ester synthesis, two carbons (a CH2 and a COOH)
can be appended to virtually any primary or secondary alkyl halide.
88
An example of a malonic ester synthesis is shown below. Reaction of benzyl bromide with diethylmalonate in
ethoxide/ethanol yields the alkylated product. Acidification hydrolyzes the esters and the intermediate diacid decarboxylates
to form the final product, 3-phenylpropanoic acid. The red line in the figure shows the bond which was formed in the reaction
and the benzyl unit and the -CH2COOH (from the malonic ester) can be clearly identified.
Identifying the alkyl halide necessary for a malonic ester synthesis simply requires you to remember that the carboxyl group
and the carbon will come from the malonic ester, and the remainder of the molecule must come from the alkyl halide. For
example, 3-methyl-3-phenylpropanoic acid can be prepared using (1-bromoethyl)benzene, as shown below:
2-Methylpropanoic acid can be prepared by alkylating diethylmalonate twice with bromomethane,
89
and 4,4-diphenylbutanoic acid can be prepared by alkylation with (2-bromo-1-phenylethyl)benzene.
The Acetoacetic Ester Synthesis

In addition to malonic esters, esters of acetoacetic acid (3-oxobutanoic acid) are also commonly used for these reactions and
the reactions are generally referred to as the acetoacetic ester synthesis. The hydrogens of ethyl acetoacetate have a pKa
of about 10, and in the presence of ethoxide in ethanol, it is completely converted to the enolate anion. Again, if an alkyl
halide is present, this enolate anion can undergo an SN2 reaction to give a mono-alkyl acetoacetic ester.
90
Acid hydrolysis generates a keto carboxylic acid. These are unstable, and undergo decarboxylation in the acidic solution to
give the enol, which isomerizes to give the final product, a methyl ketone. You should note that three carbons of the
acetoacetic ester have been added to the carbon skeleton of the alkyl halide which was used in the first step. Thus,
using the acetoacetic ester synthesis, three carbons (a CH2, a carbonyl and a CH3) can be appended to virtually any primary,
allyl or benzyl halide.
An example of an acetoacetic ester synthesis is shown below. Reaction of 1-bromopropane with ethylacetoacetate in
ethoxide/ethanol yields the alkylated product. Acidification hydrolyzes the ester and the intermediate keto acid
decarboxylates to form the final product, 2-hexanone. The red line in the figure shows the bond which was formed in the
reaction and the propyl unit and the three carbons from the acetoacetic ester can be clearly identified.
The alkylation of less acidic hydrogens can be accomplished using LDA to completely convert the carbonyl compound
into the desired enolate anion. This is then reacted with an alkyl halide to give the alkylated product.
91
This reaction is useful with ketones, aldehydes, esters and nitriles, as shown below:
92
Carbonyl Condensation Reactions
The Aldol Condensation

As described previously, aldehydes and ketones enolize in base to produce a small equilibrium concentration of the
corresponding enolate anion. If the concentration of carbonyl compound is sufficiently high, this enolate anion can function
as a nucleophile towards the carbonyl carbon of other aldehydes in ketones in the solution. The result is the formation of a
bond between the carbon of one mole of carbonyl compound and the carbonyl carbonyl of a second, to give a hydroxy
aldehyde or ketone. This condensation reaction between two moles of an aldehyde or ketone is called the aldol
condensation.
The reaction is general for both aldehydes and ketones, bearing at least one hydrogen.
The hydroxy carbonyl compounds which are formed are stable in base, but readily dehydrate in acid solution to give
unsaturated carbonyl compounds.
93
As an example of the use of an aldol reaction in synthesis, consider the preparation of 2-ethyl-2-
hexenal. This molecule is an unsaturated aldehyde. We can make these by the dehydration of
hydroxy aldehydes in aqueous acid. The required hydroxy aldehyde, in turn can be prepared by the
aldol condensation of two moles of butanal in aqueous base. To determine the structure of the required
aldehyde, simply split the compound at the bond between the hydroxyl group and the carbon of the
carbonyl, as shown on the right. As you can see, splitting like this breaks the molecule into two, four-
carbon parts, both with an oxygen bonded to carbon #1.
Drawing the structure of the reacting enol-aldehyde pair, as shown above, the mechanism of the condensation becomes clear.
It is also possible to utilize two different aldehydes or ketones in an aldol-type condensation reaction. In order to minimize
self-condensations, generally one reactant is chosen which has no hydrogens, and that reactant is maintained in large
excess over the second reactant (which will have hydrogens and can form the enolate anion). An example of this is the
synthesis of 4-phenyl-3-buten-2-one, shown on the right. This unsaturated ketone can be prepared by dehydration of the
hydroxy ketone, as shown. Splitting this between the carbon and the hydroxyl group, it is evident that it can be prepared
by the condensation of the enol of 2-propanone (acetone) and benzaldehyde, as shown below.
This molecule can also be prepared by the condensation of ethyl acetoacetate with benzaldehyde, followed by dehydration
and decarboxylation, as shown below. This type of mixed aldol does not generate side-products due to self-condensation of
the acetoacetate since the hydrogen of this molecule is acidic and it is converted essentially entirely to the enolate anion in
the basic solution.
94
The Claisen Condensation
Esters, like aldehydes and ketones, enolize in base to produce a small equilibrium concentration of the corresponding enolate
anion. As in the aldol condensation, this enolate anion can function as a nucleophile towards the carbonyl carbon of another
mole of ester, and the result is the formation of a bond between the carbon of one mole of ester and the carbonyl of a
second, to give a tetrahedral intermediate, as shown below for ethyl acetate. Expulsion of ethoxide from this intermediate re-
forms the carbonyl and generates the condensation product, ethyl acetoacetate. This condensation reaction between two
moles of an ester is called the Claisen condensation.
It is also possible to utilize two different esters in a Claisen-type condensation reaction (a mixed Claisen condensation). In
order to minimize self-condensations, generally one reactant is chosen which has no hydrogens, and that reactant is
maintained in large excess over the second reactant (which will have hydrogens and can form the enolate anion). An
example of this is the synthesis shown below. This keto ester can be prepared by elimination of ethoxide from the
tetrahedral intermediate formed by the addition of ethoxide anion to the ketone carbonyl. Splitting this tetrahedral
intermediate between the carbon of the ester portion of the molecule and the tetrahedral center, it is evident that it can be
prepared by the condensation of the enol of ethyl acetate and ethyl benzoate, as shown below.
95
The keto esters which are formed in a Claisen condensation are stable in base, but readily decarboxylate in acid solution to
give simple ketones.
The decarboxylation reaction involves the hydrolysis of the ester to generate a keto carboxylic acid. These can undergo
acid-catalyzed decarboxylation by the mechanism shown above to give the intermediate enol, which rapidly converts to the
corresponding ketone. If the Claisen condensation involved the reaction of two moles of the same ester, the product formed
will be a symmetrical ketone and the Claisen condensation is an excellent method for the preparation of symmetrical
ketones. If a mixed Claisen condensation was utilized, more complex, unsymmetrical ketones can be prepared.
As an example of the use of a Claisen condensation in synthesis, consider the preparation of 2,6-dimethyl-4-heptanone. This
molecule is a symmetrical ketone. We can make these by the decarboxylation of keto acid in aqueous acid. The required
keto acid, in turn can be prepared by the Claisen condensation of two moles of ethyl 3-methylbutanoate in the presence of
ethoxide anion. Remember, to determine the structure of the required ester, simply add ethoxide to the ketone carbonyl to
form the tetrahedral intermediate, shown on the right, and split the compound at the bond between the tetrahedral center and
the carbon of the ester portion of the molecule. The complete synthesis is shown below.
96
Conjugate Addition Reactions
In previous chapters, we have examined conjugate addition reactions of unsaturated ketones and aldehydes, and these
reactions are summarized in the first three examples shown below.
The last example utilizes an enolate anion as a nucleophile towards an unsaturated carbonyl to give, in this example, a
branched tri-ketone. The formation of this compound by the conjugate addition follows the mechanism shown below. The
enolate simply adds to the carbon, and then the intermediate enolate collapses, picking up a proton on the carbon to give
the final product.
97
A variety of compounds with acidic hydrogens are suitable nucleophiles for conjugate addition, as shown in the examples
below.
Nitroalkanes are also suitable nucleophiles, since the carbon is acidified by the adjacent nitrogen cation and the anion is
resonance stabilized.
Enamines, likewise, can be utilized as nucleophiles in these reactions, yielding di-ketones.
98
Aliphatic & Aromatic Amines
Nomenclature of Aliphatic Amines
Simple amines are named as derivatives of the parent alkane, using the suffix -amine, or by using -
amino to name a numbered substituent, using the following rules:
1. Select the longest continuous carbon chain, containing the amino group, and derive the parent name by replacing the
-e ending with -amine, or by naming the nitrogen as an amino substituent.
2. Number the carbon chain, beginning at the end nearest to the amino group, or, to give the lowest number at the
first point of difference.
Thus for the following example, you would number from the end closest to the nitrogen, generating the names, 3-
methylpentanamine (or 1-amino-3-methylpentane) and 5-methyl-2-hexanamine (or 2-amino-5-methyl-2-hexane),
respectively.
In this example, however, you number to give the lowest number at the first point of difference, generating the name, 5-
amino-2,3-dimethylhexane (not 2-amino-4,5-dimethylhexane).
Some examples:
99
Multiple substituents on the nitrogen are named using simple multipliers:
Amines are further categorized as "primary, secondary, tertiary and quarternary" based on the number of substituents on the
nitrogen:
Reactions of Amines
100
Reactions of Aliphatic Amines
Simple amines and ammonia are strong nucleophiles and will undergo an S N2 reaction with alkyl halides (or alkyl groups
with "good leaving groups") to give further substitution on the nitrogen, as described previously. They will also react with
activated carbonyl compounds to undergo acyl transfer reactions; thus amides are readily formed by the reaction of amines
with acid halides, acid anhydrides or carboxylate esters.
The reaction of an amine with a sulfonyl halide forms the sulfonamide. A common reagent utilized in this reaction is p-
toluenesulfonyl chloride, producing the corresponding p-toluenesulfonamide.
The base solubility of sulfonamides forms the basis of the Hinsberg test, for distinguishing primary, secondary and tertiary
amines; primary p-toluenesulfonamides undergo ionization in strong base to give the base-soluble anion, secondary p-
toluenesulfonamides lack the acidic hydrogen and do not form a soluble anion; tertiary amines would yield highly unstable
cationic quarternary sulfonamides, and generally do not react at all. Thus, the formation of a base-soluble sulfonamide
indicates the presence of a primary amine.
101
Reaction of primary amines with an excess of iodomethane converts the primary amine into the quarternary ammonium salt.
The cationic nitrogen which is now formed is a good leaving group, and will undergo E2 elimination on reaction with Ag 2O
to give the alkene, in a reaction known as the Hofmann Elimination.
The Hofmann Elimination is unusual for an E2 elimination because the least substituted alkene is typically formed.
Amides and acid azides can also be converted to amines using the Hofmann and Curtius rearrangements, respectively. Both
the amide and acyl azide can be prepared from an intermediate acid halide, and the reaction results in the shortening of the
alkyl chain by one carbon (the carbonyl is lost as CO2).
102
Reactions of Aryl Amines
Aryl amines, like aliphatic amines and ammonia, are strong nucleophiles and will undergo an S N2 reaction with alkyl halides
(or alkyl groups with "good leaving groups") to give further substitution on the nitrogen, as described previously. They will
also react with activated carbonyl compounds to undergo acyl transfer reactions; thus amides are readily formed by the
reaction of amines with acid halides, acid anhydrides or carboxylate esters. The conversion of an aryl amine into an amide is
a convenient method for limiting ring bromination to the para- position on the ring, the intermediate amide being simply
hydrolyzed in a second step.
This intermediate step is necessary, since the free amine highly activates the ring to substitution, yielding tri-substitution.
Perhaps the most useful reactions of aryl amines involve the intermediate conversion into the corresponding diazonium salt
by reaction with nitrous acid.
103
These diazonium salts undergo a series of replacement reactions, collectively known as the Sandelmyer Reaction to give
aryl nitriles or aryl halides. A copper salt is generally required to catalyze the reaction, with the exception of iodination,
which occurs spontaneously.
Aryl diazonium salts also undergo reduction to yield the arene on reaction with phosphouous acid (not phosphoric), and
hydrolysis in the presence of aqueous acid to give the corresponding phenol. The cationic nitrogen of diazonium salts also
adds to the para- position of highly activated aryl rings (generally aryl amines and phenols) to give coupling products, as
shown below.
Reactions that Yield Amines
Reactions that Yield Aliphatic Amines

Simple amines and ammonia are strong nucleophiles and will undergo an S N2 reaction with alkyl halides (or alkyl groups
with "good leaving groups") to give further substitution on the nitrogen. Ammonia reacts with alkyl halides to give a mixture,
consisting largely of the corresponding primary and secondary amines, with a trace of tertiary and quarternary amines. Since
a mixture is obtained, this is generally a poor method for the preparation of amines.
104
Better methods for the preparation of primary amines involve the reduction of a intermediate alkyl azide, or the Gabriel
Synthesis, involving an intermediate phtalimide. In the first method, the alkyl halide reacts with azide anion in a simple S N2
reaction to give the intermediate alkyl azide. This is generally not isolated, but is reduced immediately with LiAlH 4 to give
the corresponding primary amine.
In the Gabriel Synthesis, pthalimide anion is reacted with the alkyl halide to give the intermediate N-substituted pthalimide.
On acid hydrolysis, this gives pthalic acid and the corresponding primary amine.
Primary amines can also be prepared by the reduction of two other functional groups; nitriles and amides. The reduction of a
nitrile by LiAlH4 gives the primary amine, as shown below. Reduction of a an amide can yield a primary, secondary or
tertiary amine, depending on the amide.
105
Amines can also be prepared by the process of reductive amination of aldehydes and ketones. An aldehyde or ketone will
react with ammonia to give an intermediate imine. Reduction of this imine with Raney Ni/H2 gives the corresponding amine.
Primary and secondary amines can also be utilized in reductie amination reactions, typically using cyanoborohydride
(NaBH3CN) to trap the intermediate immonium ion.
106

Functional Group Nomenclature &amp; Reactions

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Functional Group Nomenclature &amp; Reactions

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Functional Group Nomenclature & Reactions

Common Substituent Names:

 an isopropyl side-chain can also be named (1-methylethyl),

Conformations of Alkanes & Cycloalkanes

(Click on the icon above to view the movie)

(Click on the icon above to view the movie)

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1. Find the longest chain containing the alkene

4. Assign stereochemistry using the E-Z designation

The rules for assigning E-Z designations are as follows:

For hydrocarbons, the process is simple:

C6H12 is 2 short of C6H14

C4H6 is 4 short of C4H10 2 DU

C7H14 is 2 short of C7H16 1 DU

C6H10 is 4 short of C6H14 2 DU

C8H8 is 10 short of C8H18 5 DU

C7H14 is 2 short of C7H16 1 DU

C12H14 is 12 short of C12H26

C6H10O "C6H10" which is 4 short of C6H14 2 DU

C5H9N "C5H8" which is 4 short of C5H12 2 DU

C6H1?N "C6H12" which is 2 short of C6H14 1 DU

C6H13N4 "C6H8" which is 6 short of C6H14 3 DU

C8H8O "C8H8" which is 10 short of C8H18 5 DU

Addition of Halogen Acids to Alkenes

Addition of Halogen to Alkenes

Click on any reaction to check your answer.

Addition of Halogen Acids to Alkenes

Addition of Halogen to Alkynes

Alkyl Halides; Substitution & Elimination Reactions

Nomenclature of Alkyl Halides

Several simple examples are shown below:

Nucleophilic Substitution Reactions

Conjugated Dienes: Introduction & Nomenclature

As with simple alkenes:

The rules for assigning E-Z designations are as follows:

Conjugated Dienes: Ionic Addition Reactions

 The 1,2- addition product forms rapidly at low temperatures;

Conjugated Dienes: Cycloaddition Reactions

Arenes: Aromatic Systems and the 4n+2 Rule

Arenes: Electrophilic Aromatic Substitution

Orientation Effects in Electrophilic Aromatic Substitution

Arenes: Reactions of Aryl Side-Chains

Alcohols & Ethers: Nomenclature

The Grignard Reaction

Preparation of Alcohols by Addition of Grignard Reagents to Carbonyl Compounds

Aldehydes & Ketones: Nomenclature

2. The parent chain selected must contain the carbonyl group.

5. When an aldehyde is a substituent on a ring, it is referred to as a -carbaldehyde group.

Reactions that Yield Aldehydes & Ketones

Some examples of common imine-forming reactions are given below:

Some examples of acetal and ketal formation are given below:

Reduction of simple aldehydes and ketones

Nomenclature of Carboxylic Acids

Several simple examples are shown below:

Reactions which Yield Carboxylic Acids

Reactions of Carboxylic Acids

Acyl Derivatives (Carboxylic Acid Derivatives)

Nomenclature of Carboxylic Acid Derivatives

Several simple examples are shown below:

Several simple examples are shown below:

Several simple examples are shown below:

Several simple examples are shown below:

Several simple examples are shown below:

Functional Group Nomenclature & Reactions

Functional Group Nomenclature & Reactions