NOTE 2:

ORGANIC SYNTHESIS

The ultimate goal of Organic Synthesis is to assemble an organic compound (target) from
readily available starting materials and reagents in the most efficient way. This process
usually begins with the design of a synthetic plan (Strategy).

Oxidation and Reduction in Organic Synthesis

In ionic and free radical reactions, oxidation and reduction are defined as processes by which
an element undergoes a net loss or gain of electrons, respectively. The concept as applied to
organic covalent compounds, where elements share electrons rather than losing or gaining
them is the same, but it’s frequently simplified and narrowed down to make it easier to
recognize these processes. Therefore it must be kept in mind that, while the following
definition is grossly simplified, it serves the goal of quickly identifying oxidation and
reduction processes in many organic reactions.

In reference to organic molecules, oxidation is a process by which a carbon atom gains

bonds to more electronegative elements, most commonly oxygen. Reduction is a process by
which a carbon atom gains bonds to less electronegative elements, most commonly
hydrogen.

The following chart summarizes these concepts when applied to organic transformations. [ox]
stands for oxidation, and [red] stands for reduction.

Some points must be noted.

 First, a gain or loss of bonds means simply more or less bonds. The double bond
counts as two bonds and the triple bond counts as three bonds. Thus in the carbonyl
 group (C=O) carbon is considered to have two bonds to oxygen. Therefore, this
carbon has a higher oxidation state than the alcohol carbon, which has only one bond
to oxygen. In routine terminology, it is said that the aldehyde is a more highly
oxidized functional group than the alcohol. Oxidation reactions are therefore those
in which the central carbon of a functional group is transformed into a more
highly oxidized form, and reduction reactions are those in which the central
carbon is transformed into a more highly reduced form.
 Second, there can be several functional groups where the central carbon has the same
oxidation state. For example, the carbons bonded to oxygen in alcohols and ethers
have the same oxidation state. Likewise for aldehydes and their hydrated forms, and
for carboxylic acids and their derivatives. However, most references to oxidation and
reduction reactions in organic chemistry textbooks involve the functional groups
presented in the chart above.

The chart presented here shows the oxidation and reduction states for a molecule that
contains only one carbon. But most organic compounds contain more than one carbon. The
maximum oxidation state that a particular carbon can attain depends on how many other
carbons it must remain attached to. For example, a molecule with two carbon atoms could not
be oxidized all the way to carbon dioxide because the carbon atom in CO 2 must have four
bonds to oxygen, leaving no room for bonds to other carbons. The maximum oxidation
state that a carbon can attain decreases gradually as the number of bonds to other
carbons increases. Thus, the maximum oxidation state possible for a carbon that’s bonded to
one other carbon is the carboxylic acid stage, and so on. The following chart illustrates this
idea.
Guide on oxidation state of carbon atoms

For carbon bonded to another carbon, the oxidation state is unaffected. So

a carbon attached to 4 carbons has an oxidation state of zero. So unlike
metals, which are almost always in a positive oxidation state, the oxidation
state of carbon can vary widely, from -4 (in CH4) to +4 (such as in CO2).

Definition of oxidation state for carbon

As we begin to look at organic redox reactions, it is useful to consider how we define

the oxidation state for carbon. Most of the redox reactions in this chapter involve a
change in the oxidation state of the carbon bearing the functional group. To
calculate the oxidation state for carbon, use the following guidelines:

1. In a C-H bond, the H is treated as if it has an oxidation state of +1. This means
that every C-H bond will decrease the oxidation state of carbon by 1.
2. For carbon bonded to a more electronegative non-metal X, such as nitrogen,
oxygen, sulfur or the halogens, each C-X bond will increase the oxidation state
of the carbon by 1. (Certain non-metals are less electronegative than carbon,
such as phosphorus, silicon or boron, but bonds from carbon to these elements
are much less common.)
3. For carbon bonded to another carbon, the oxidation state is unaffected. So a
carbon attached to 4 carbons has an oxidation state of zero.

So unlike metals, which are almost always in a positive oxidation state, the oxidation
state of carbon can vary widely, from -4 (in CH4) to +4 (such as in CO2). Here are
some examples.
ORGANOMETALLICS IN ORGANIC SYNTHESIS

Organometallic synthesis, or organometallic chemistry, represents a broad scope of use in

synthetic organic chemistry. Organometallic synthesis refers to the process of
creating organometallic compounds. Organometallic chemistry is among the most actively
researched areas in organic, inorganic, biochemical, and catalytic chemistry.

Organometallic is a molecule that contains a metal atom bonded to a carbon atom.

Compounds with, for example, metal-nitrogen, metal-oxygen, metal-phosphorus bonds
are defined as coordination complexes but are often described as “organometallic”.

Organometallic compounds may contain group 1 alkali, group 2 alkali earth, group 3-12
transition, and 13-15 main group elements, as well as metalloids, such as boron and silicon.
The large array of elements that can form organometallic compounds result in vast research
in procedures for organometallic synthesis. There are also research efforts in the use of
organometallic reagents in the synthesis of ever-more complex and tailored organic
compound, for which organometallic reagents drive specific bonding and/or catalyze
reactions.
Organometallic reagents are frequently used to synthesize organic molecules since they drive
specific bonding and/or catalyze reactions. Some of these reactions are difficult or
impractical to carry out by other means. In most organic compounds, carbon atoms tend to be
electrophilic, but in organometallic compounds, because the metal atom is typically less
electronegative than the carbon it is attached to, the carbon acts as a nucleophile of varying
strength. When a strongly electronegative metal is involved, the charge distribution is such
that the compound is more ionic in nature and can be strongly reactive.

For example, in organolithium compounds, the C-Li bond is more ionic and the C is more
negatively polarized. The bonds in organolithium compounds are more strongly polarized
than in their organomagnesium analogs (Grignard reagents) making organolithium a
stronger nucleophile and more reactive compared to the Grignard.

Both organomagnesium and organolithium reagents are strong bases for deprotonation and
readily form C-C bonds, as well as drive many other organic reactions.

Examples of Organometallic Compounds

The number of organometallic compounds is vast and cover most of the major elements in
the periodic groups. Most examples of organometallics are either in the main group elements
or the transition group elements.

Examples of important organometallics include organolithium, organoborane (period 2

elements), organomagnesium, organosilicon (period 3 elements), organoiron, organocobalt
(period 4 elements), organoruthenium, organotin (period 5 elements), organoplatinum,
organoiridium (period 6 elements).
 How are Organometallic Compounds Synthesized?

There are numerous ways to synthesize organometallics:

 One of the most used methods to synthesize an organometallic compound is to react the
pure metal with specific organic molecules. Examples of this type of synthesis are two of
the most frequently used organometallic reagents, organolithium and organomagnesium, for
which the metal is reacted with an alkyl- or aryl-halide to form the desired reagent.

 In double-decomposition reactions, metal halides exchange with alkylating reagents to

yield the organometallic reagent. Carbon monoxide reacts with transition metals to form
metal carbonyls.

 Decarbonylation of a metallo-organic will produce an organometallic compound.

 Hydrometalation is a synthesis method in which a molecule with a metal -hydrogen bond

reacts with an organic molecule containing a double bond, forming a organometallic with a
metal-carbon bond.

Various addition and elimination reactions form organometallic compounds from metallo-
organic molecules. Choosing the optimal synthesis method is often informed by inline
analytical techniques to ensure safe and efficient process development.

TERMINOLOGIES IN ORGANIC SYNTHESIS

Disconnection: An analytical operation, which breaks a bond and converts a molecule into a
possible starting material. The reverse of a chemical reaction. Symbol ⇒ and a curved line
drawn through the bond being broken. Called a dislocation by some people.

FGI: Functional Group Interconversion: The operation of writing one functional group for
another so that disconnection becomes possible. Again the reverse of a chemical reaction.
Symbol ⇒ with FGI written over it.
Reagent: A compound which reacts to give an intermediate in the planned synthesis or to
give the target molecule itself. The synthetic equivalent of a synthon.

Synthetic Equivalent: A reagent carrying out the function of a synthon which cannot itself
be used, often because it is too unstable.

Synthon: A generalised fragment, usually an ion, produced by a disconnection. (Some people

also use synthon for a synthetic equivalent).

Target Molecule: The molecule whose synthesis is being planned. Usually written TM and
identified by the frame number.

(a) Define synthesis 2 mks.

(b) Briefly explain the following terms

i. Synthon ii. Target molecule iii. Functional group interconversion 3 mks each

(c). Structurally describe the method of formation of C-C bond formation using Michael’s
addition reaction 9 mks

SECTION C

Q5 (a). Explain the reason why organic compounds are synthesized. 6 marks

(b) Using Ritter reaction, explain the formation of carbon to Nitrogen bonds in organic
synthesis. Show the reaction mechanism 10 mks

(c) Highlight how oxidation and reduction aids the synthesis of organic compounds 4 mks

Q6. A C-C bond of an alkene is synthesized during a transformation called the Wittig
reaction. Structurally explain the synthetic process of a Wittig reaction 10 mks

(b) What are the importance of organometallic compounds in organic synthesis 5 mks
(c) Describe Stork enamine synthesis. What are enamines? 5 mks