Srood O. Rashid 1 - suli-pharma.com fileDr. Srood Omer Rashid 4 Alkanes have only carbon atoms...

1Srood O. Rashid

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2Dr. Srood Omer Rashid 2

Ch.4: Alkanes and Cycloalkanes

3Dr. Srood Omer Rashid

4.1 Classes of Hydrocarbons

Hydrocarbons contain only carbon and hydrogen.

Saturated hydrocarbons contain only carbon–carbon single bonds.

Unsaturated hydrocarbons contain carbon–carbon multiple bonds.


Alkanes have only carbon atoms bonded in chains of atoms. Some carbon

atoms bonded to more than two other carbon atoms. The general formula for an

alkane is CnH2n+2.

Cycloalkanes have only carbon atoms bonded in a ring of atoms.


Compounds without rings are acyclic; compound with rings are cyclic.

Other atoms may be found in some rings. Atoms other than carbon within rings are

heteroatoms, and the compounds are heterocyclic.

A carbon atom is classified as primary (1°), secondary (2°), or tertiary (3°) when it

has 1, 2, or 3 alkyl groups, respectively, bonded to it. A carbon atom is quaternary

(4°) when it has 4 alkyl groups bonded to it.


4.3 Nomenclature of Alkanes

The IUPAC nomenclature rules in this section form the foundation on which we will

base all other nomenclature. Here is a brief summary.

In the early nineteenth century, organic compounds were often named at the whim of

their discoverers. Here are just a few examples:

A large number of compounds were given names that became part of the common

language shared by chemists. Many of these common names are still in use today.

Today, Names produced by International Union of Pure and Applied Chemistry (IUPAC)

rules are called systematic names. There are many rules, and we cannot possibly

study all of them.


1. Locate the longest carbon chain, called the parent chain.

2. Identify the groups that are substituents attached to the parent chain.

3. Number the parent chain to give the branching carbon atoms and other substituents

the lowest possible numbers.

4. Use a prefix to the name of the parent chain to identify the name and location of all

branches and other substituents.

5. Each substituent must be assigned a number to indicate its position. Thus, if two

methyl groups are bonded to C-2 in a chain of carbon atoms, the name “2-dimethyl” as

part of the prefix is incorrect; two methyl groups bonded to C-2 must be designated as

2,2-dimethyl. To determine the numbering of the substituents to use in the prefix, choose

the point of first difference.

6. List the names of substituents alphabetically. Note that the prefixes di, tri, etc., do not

affect the alphabetic method of listing alkyl groups. For example, ethyl is listed before

dimethyl because it is the “e” of ethyl that takes precedence over the “m” of methyl.

7. The most common alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, sec-butyl,

isobutyl, and tert-butyl.


Selecting the Parent Chain


The first step in naming an alkane is to identify the longest chain, called the parent chain

If there is a competition between two chains of equal length, then choose the chain with

the greater number of substituents. Substituents are the groups connected to the

parent chain:


Q) Identify and name the parent in each of the following compounds:

Naming SubstituentsOnce the parent has been identified, the next step is to list all of the substituents:


When an alkyl group is connected to a ring, the ring

is generally treated as the parent:

However, this is only true when the ring is

comprised of more carbon atoms than the alkyl

group. In the example above, the ring is comprised

of six carbon atoms, while the alkyl group has only

three carbon atoms. In contrast, consider the

following example in which the alkyl group has

more carbon atoms than the ring. As a result, the

ring is named as a substituent and is called a

cyclopropyl group.


Q) For each of the following compounds, identify all groups that would be considered

substituents, and then indicate how you would name each substituent.


Naming Complex Substituents

Naming branched alkyl substituents is more complex than naming straight-chain

substituents. For example, consider the following substituent:

How do we name this substituent? It has five carbon atoms, but it cannot simply be

called a pentyl group, because it is not a straight-chain alkyl group. In situations like

this, the following method is employed: Begin by placing numbers on the substituent,

going away from the parent chain:

This group is called a (2-methylbutyl)

Some complex substituents have common names. These common names are so

well entrenched that IUPAC allows them. It would be wise to commit the following

common names to memory, as they will be used frequently throughout the course.


An alkyl group bearing three carbon atoms can only be branched in one way, and it

is called an isopropyl group:

Alkyl groups bearing four carbon atoms can be branched in three different ways:


Alkyl groups bearing five carbon atoms can be branched in many more ways. Here are

two common ways:

Note: The following substituent is called a phenyl group


4.7 For each of the following compounds, identify all groups that would be considered

substituents, and then indicate the systematic name as well as the common name for

each substituent:


4.10 Provide a systematic name for each of the following compounds below:


Naming Bicyclic Compounds

Compounds that contain two fused rings are called bicyclic compounds, and they can

be drawn in different ways:

The second drawing style implies the three dimensionality of the molecule, a topic that

will be covered in more detail in the upcoming chapter. For now, we will focus on

naming bicyclic systems, which is very similar to naming alkanes and cycloalkanes.

We follow the same four-step procedure outlined in the previous section, but there are

differences in naming and numbering the parent. Let’s start with naming the parent.

For bicyclic systems, the term “bicyclo” is introduced in the name of the parent.

The problem is that this parent is not specific enough. To illustrate this, consider the

following two compounds, both of which are called bicycloheptane:

bicycloheptane


Both compounds consist of two rings and seven carbon atoms. Yet, the compounds

are clearly different, which means that the name of the parent needs to contain more

information. Specifically, it must indicate the way in which the rings are constructed

(the constitution of the compound). In order to do this, we must identify the two

bridgeheads. These are the two carbon atoms where the rings are fused together:

There are three different paths connecting these two bridgeheads. For each path,

count the number of carbon atoms, excluding the bridgeheads themselves. In the

compound above, one path has two carbon atoms, another path has two carbon

atoms, and the third (shortest path) has only one carbon atom. These three numbers,

ordered from largest to smallest, [2.2.1], are then placed in the middle of the parent

surrounded by brackets:


If a substituent is present, the parent must be numbered properly in order to assign

the correct locant to the substituent. To number the parent, start at one of the

bridgeheads and begin numbering along the longest path, then go to the second

longest path, and finally go along the shortest path. For example, consider the

following bicyclic system:


6-methylbicyclo[3.2.1]octane

4.12 Name each of the following compounds:


Pharmaceuticals have three important names:

(1) trade names, (2) generic names, and (3) systematic IUPAC names. Table 4.3 lists

several common drugs whose trade names are likely to sound familiar.


Constitutional Isomers of Alkanes


Ex: The constitutional isomers C6H14

4.14 For each pair of compounds, identify whether they are constitutional isomers or

two representations of the same compound:

To avoid drawing the same compound

twice, it is helpful to use IUPAC rules to

name each compound.


4.4 Relative Stability of Isomeric Alkanes

In order to compare the stability of constitutional isomers, we look at the heat liberated

when they each undergo combustion. For an alkane, combustion describes a reaction in

which the alkane reacts with oxygen to produce CO2 and water. Consider the following

example:

Combustion can be conducted under experimental conditions using a device called a

calorimeter, which can measure heats of combustion accurately. Careful measurements

reveal that the heats of combustion for two isomeric alkanes are different, even though

the products of the reactions are identical:

Alkanes are among the least reactive types of organic compounds. They do not react

with common acids or bases, nor do they react with common oxidizing or reducing

agents. Alkanes do, however, share one type of reactivity with many other types of

organic compounds: they are flammable.


By comparing the amount of heat given off by each combustion process, we can

compare the potential energy that each isomer had before combustion. This analysis

leads to the conclusion that branched alkanes are lower in energy (more stable) than

straight-chain alkanes.

Heats of combustion are an important way to determine the relative stability of

compounds.

27Dr. Srood Omer Rashid

ΔH= -2750 kJ mol–1 (657 kcal mol–1)

27

4.4 .1 Combustion and the Chemistry of Life Processes

The amount of energy available from the combustion of a mole of solid glucose, if it

were released solely as heat, is 2750 kJ mol–1 (657 kcal mol–1). [Compare this to the

energy available from the combustion of the six-carbon alkane, hexane: 4163 kJ mol–1

(995 kcal mol–1)].

The biological “combustion” of glucose does not involve lighting a match and burning it.

Rather, the living organism uses a series of chemical reactions that take glucose apart,

one or two bonds at a time, and stores the energy liberated at each stage by forming

molecules that can be tapped as energy sources when needed, such as adenosine

triphosphate (ATP).


The human body recovers the energy from glucose “combustion” with efficiencies that

vary from 40–60%, depending on conditions. Given that human metabolism is 2–3 times

as efficient as an automotive engine, more energy is recovered from the “combustion” of

a mole of glucose than an internal-combustion engine recovers from a mole of 2,2,4-

trimethylpentane!


4.5 Sources and Uses of Alkanes

Most alkanes come from petroleum, or crude oil. (The word petroleum comes from the

ancient Greek word for “rock” (petra) and the Latin word for “oil” (oleum); thus, “oil from

rocks.”) Petroleum is a dark, viscous mixture of hundreds of hydrocarbons, composed

mostly of alkanes and aromatic hydrocarbons (benzene and its derivatives) that are

separated by a technique called fractional distillation. In fractional distillation, a

mixture of compounds is slowly boiled; the vapor is then collected, cooled, and

recondensed to a liquid.


Molecular Representations

We will use many different kinds of

drawings to represent the three

dimensional geometry of atoms. The

most common method is a bond-line

structure that includes wedges and

dashes to indicate three dimensionality.

These structures are used for all types of

compounds, including acyclic, cyclic, and

bicyclic compounds. A wedge represents

a group coming out of the page, and a

dash represents a group going behind

the page.

Methods of Drawing Conformations

1. Newman projections

2. Line-and-wedge structures

3. Sawhorse projections


4.6 Conformations of Alkanes and Drawing Newman Projections

To completely describe the shapes of molecules that are more complex than the

diatomic (HCl), triatomic (NH3), tetra-atomic (CH4) molecules, we need to specify not

only the bond lengths and bond angles, but also the spatial relationship of the bonds on

adjacent atoms.

We will now turn our attention to the way in which molecules change their shape with

time. Rotation about C-C single bonds allows a compound to adopt a variety of possible

three dimensional shapes, called conformations.

Some conformations are higher in energy, while others are lower in energy. In order to

draw and compare conformations, we will need to use a new kind of drawing—one

specially designed for showing the conformation of a molecule. This type of drawing is

called a Newman projection (see Figure 4.2 for drawing newman project for ethane).

Figure 4.2

Three drawings of ethane:

(a) wedge and dash,

(b) sawhorse, and

(c) a Newman projection.

To understand what a Newman projection represents, consider the wedge and dash

drawing of ethane in Figure 4.2. Begin rotating it about the vertical axis drawn in gray so

that all of the red H’s come out in front of the page and all of the blue H’s go back behind

the page. The second drawing (the sawhorse) represents a snapshot after 45° of

rotation, while the Newman projection represents a snapshot after 90° of rotation.


One carbon is directly in front of the other, and each carbon atom has three H’s attached

to it (Figure 4.3). The point at the center of the drawing in Figure 4.3 represents the front

carbon atom, while the circle represents the back carbon. We will use Newman

projections extensively throughout the rest of this chapter, so it is important to master

both drawing and reading them.

Figure 4.3

A Newman projection of ethane,

showing the front carbon and the

back carbon.

Q) Draw a Newman projection of the following compound, as viewed from the

angle indicated:

Newman projection is a type of planar projection along one bond, which we’ll call

the projected bond. Generally, the carbon–carbon bond is the projected bond.


2) Identify the three groups connected to the back carbon atom.

Solution1) Identify the three groups connected to the front carbon atom.

Identify the front and back carbon atoms. From the angle of the observer, the front and

back carbon atoms are:


3) Draw the Newman projection

Now we put both pieces of our drawing together:

4.16 In each case below, draw a Newman projection as viewed from the angle indicated:


Solution

4.17 Draw a bond-line structure for each of the following compounds:


Solution

4.18 Determine whether the following compounds are constitutional isomers:


4.7 Conformational Analysis of Ethane and Propane

Ethane: Consider the two hydrogen atoms shown in red in the Newman projection of ethane(Figure 4.4). These two hydrogen atoms appear to be separated by an angle of 60°. This angle iscalled the dihedral angle or torsional angle. This dihedral angle changes as the C-C bondrotates—for example, if the front carbon rotates clockwise while the back carbon is heldstationary. The value for the dihedral angle between two groups can be any value between 0°and 180°. Therefore, there are an infinite number of possible conformations. Nevertheless,there are two conformations that require our special attention: the lowest energy conformationand the highest energy conformation (Figure 4.5). The staggered conformation is the lowest inenergy, while the eclipsed conformation is the highest in energy.

Figure 4.4

The dihedral angle between two

hydrogen atoms in a Newman

projection of ethane.

Figure 4.5

Staggered and eclipsed

conformations of ethane.


The difference in energy between staggered and eclipsed conformations of ethane is 12

kJ/mol, as shown in the energy diagram in Figure 4.6. Notice that all staggered

conformations of ethane are degenerate; that is, all of the staggered conformations

have the same amount of energy. Similarly, all eclipsed conformations of ethane are

degenerate.

Figure 4.6

An energy diagram showing the conformational analysis of ethane.


The difference in energy between staggered and eclipsed conformations of ethane is

referred to as torsional strain, and its cause has been somewhat debated over the

years. Based on recent quantum mechanical calculations, it is now believed that the

staggered conformation possesses a favorable interaction between an occupied,

bonding MO and an unoccupied, antibonding MO (Figure 4.7).

Figure 4.7

In the staggered conformation, favorable overlap occurs between a

bonding MO and an antibonding MO.

Dihedral Angle (Torsion Angle): The angle by which two groups are separated in a

Newman projection.


This interaction lowers the energy of the staggered conformation. This favorable

interaction is only present in the staggered conformation. When the C-C bond is rotated

(going from a staggered to an eclipsed conformation), the favorable overlap above is

temporarily disrupted, causing an increase in energy. In ethane, this increase amounts

to 12 kJ/mol. Since there are three separate eclipsing interactions, it is reasonable to

assign 4 kJ/mol to each pair of eclipsing H’s (Figure 4.8).

Figure 4.8

The total energy cost associated with the eclipsed conformation of ethane (relative

to the staggered conformation) amounts to 12 kJ/mol.

This energy difference is significant. At room temperature, a sample of ethane gas will

have approximately 99% of its molecules in staggered conformations at any given

instant.


The energy diagram of propane (Figure 4.9) is very similar to that of ethane, except that

the torsional strain is 14 kJ/mol rather than 12 kJ/mol. Once again, notice that all

staggered conformations are degenerate, as are all eclipsed conformations.

Figure 4.9

An energy diagram showing the conformational analysis of propane.


We already assigned 4 kJ/mol to each pair of eclipsing H’s. If we know that the torsional

strain of propane is 14 kJ/mol, then it is reasonable to assign 6 kJ/mol to the eclipsing

of an H and a methyl group. This calculation is illustrated in Figure 4.10.

Figure 4.10

The energy cost associated with a methyl group eclipsing a hydrogen atom

amounts to 6 kJ/mol.

4.8 Conformational Analysis of Butane Home work?

See pages 159- 163. David Klein Text book of Organic chemistry


4.19 For each of the following compounds, predict the energy barrier to rotation (looking

down any one of the C-C bonds). Draw a Newman projection and then compare the

staggered and eclipsed conformations. Remember that we assigned 4 kJ/mol to each

pair of eclipsing H’s and 6 kJ/mol to an H eclipsing a methyl group:

(a) 2,2-Dimethylpropane (b) 2-Methylpropane

Solution


4.20 In each case below, identify the highest and lowest energy conformations. In cases

where two or three conformations are degenerate, draw only one as your answer.

Solution


Drugs and Their Conformations

The drug possesses a specific three dimensional arrangement of

functional groups, called a pharmacophore. For example, the

pharmacophore of morphine is shown in red: Morphine is a very

rigid molecule, because it has very few bonds that undergo free

rotation. As a result, the pharmacophore is locked in place.

In contrast, flexible molecules are capable of adopting a variety of conformations,

and only some of those conformations can bind to the receptor. For example,

methadone has many single bonds, each of which undergoes free rotation:

Methadone is used to treat heroin addicts suffering from withdrawal symptoms.

Methadone binds to the same receptor as heroin, and it is widely believed that the

active conformation is the one in which the position of the functional groups

matches the pharmacophore of heroin

(and morphine):


This explains how it is possible for one drug to produce several physiological effects.

In many cases, one conformation binds to one receptor, while another conformation

binds to an entirely different receptor. Conformational flexibility is therefore an

important consideration in the study of how drugs behave in our bodies.

4.9 CycloalkanesIn the nineteenth century, chemists were aware of many compounds containing five-

membered rings and six-membered rings, but no compounds with smaller rings were

known.

At the end of the nineteenth century Adolph von Baeyer proposed a theory describing

cycloalkanes in terms of angle strain, the increase in energy associated with a bond

angle that has deviated from the preferred angle of 109.5°. Baeyer’s theory was based

on the angles found in geometric shapes (Figure 4.17). Baeyer reasoned that five-

membered rings should contain almost no angle strain, while other rings would be

strained (both smaller rings and larger rings). He also reasoned that very large

cycloalkanes cannot exist, because the angle strain associated with such large bond

angles would be prohibitive.

Figure 4.17

Bond angles found

in geometric shapes.


Evidence refuting Baeyer’s conclusions came from thermodynamic experiments.(Heats of Combustion)

The conclusions from these data are more easily

seen when plotted (Figure 4.18). Notice that a

six-membered ring is lower in energy than a five

membered ring, in contrast with Baeyer’s theory.

In addition, the relative energy level does not

increase with increasing ring size, as Baeyer

predicted. A 12-membered ring is in fact much

lower in energy than an 11-membered ring.


Baeyer’s conclusions did not hold because they were based on the incorrect assumption

that cycloalkanes are planar, like the geometric shapes shown earlier. In reality, the

bonds of a larger cycloalkane can position themselves three dimensionally so as to

achieve a conformation that minimizes the total energy of the compound. We will soon

see that angle strain is only one factor that contributes to the energy of a cycloalkane.

We will now explore the main factors contributing to the energy of various ring sizes,

starting with cyclopropane.

Cyclopropane

The angle strain in cyclopropane is severe. Some of this strain can be alleviated if the

orbitals making up the bonds bend outward, as in Figure 4.19. Not all of the angle strain

is removed, however, because there is an increase in energy associated with inefficient

overlap of the orbitals. Although some of the angle strain is reduced, cyclopropane still

has significant angle strain.

Figure 4.19

The C-C bonds of cyclopropane

bend outward (on the dotted red

lines) to alleviate some of the

angle strain.


In addition, cyclopropane also exhibits significant torsional strain, which can best be

seenin a Newman projection:

Notice that the ring is locked in an eclipsed conformation, with no possible way of

achieving a staggered conformation.

In summary, cyclopropane has two main factors contributing to its high energy: angle

strain (from small bond angles) and torsional strain (from eclipsing H’s). This large

amount of strain makes three-membered rings highly reactive and very susceptible to

ring-opening reactions.

Cyclobutane

Cyclobutane has less angle strain than cyclopropane. However, it has more torsional

strain, because there are four sets of eclipsing H’s rather than just three. To alleviate

some of this additional torsional strain, cyclobutane can adopt a slightly puckered

conformation without gaining too much angle strain:


Cyclopentane

Cyclopentane has much less angle strain than cyclobutane or cyclopropane. It can also

reduce much of its torsional strain by adopting the following conformation:

In total, cyclopentane has much less total strain than cyclopropane or cyclobutane.

Nevertheless, cyclopentane does exhibit some strain. This is in contrast with

cyclohexane, which can adopt a conformation that is nearly strain free. We will spend

the remainder of the chapter discussing conformations of cyclohexane.

Generally:


4.10 Conformations of Cyclohexane

Cyclohexane can adopt many conformations, as we will soon see. For now, we will

explore two conformations: the chair conformation and the boat conformation (Figure

4.20).

Figure 4.20

The chair and boat

conformations

of cyclohexane.

In both conformations, the bond angles are fairly close to 109.5°, and therefore, both

conformations possess very little angle strain. The significant difference between them

can be seen when comparing torsional strain. The chair conformation has no torsional

strain. This can best be seen with a Newman projection (Figure 4.21). Notice that all H’s

are staggered. None are eclipsed.

Figure 4.21

A Newman projection of

cyclohexane in a chair

conformation.


This is not the case in a boat conformation, which has two sources of torsional strain

(Figure 4.22). Many of the H’s are eclipsed (Figure 4.22a), and the H’s on either side of

the ring experience steric interactions called flagpole interactions, as shown in Figure

4.22 b.

Figure 4.22

(a) A Newman projection

of cyclohexane in a boat

conformation. (b) Flagpole

interactions in the boat

conformation.

The boat can alleviate some of this torsional strain by twisting (very much the way

cyclobutane puckers to alleviate some of its torsional strain), giving a conformation

called a twist boat (Figure 4.23).

Figure 4.23

The twist boat conformation of

cyclohexane.


In fact, cyclohexane can adopt many different conformations, but the most important is

the chair conformation. There are actually two different chair conformations that rapidly

interchange via a pathway that passes through many different conformations, including a

high energy half-chair conformation, as well as twist boat and boat conformations. This

is illustrated in Figure 4.24, which is an energy diagram summarizing the relative energy

levels of the various conformations of cyclohexane.

Figure 4.24

An energy diagram

showing the

conformational analysis

of cyclohexane.


4.11 Drawing Chair Conformations

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