ORGANIC CHEMISTRY

1

ORGANIC CHEMISTRY

Chapter 1: Introduction

Congratulations, you are taking Organic chemistry. It is likely that you are a science major, in a class of

students with a wide range of interests and career choices. Why is organic chemistry important? The

answer lies in the fact that every aspect of life, mammalian and non-mammalian as well as plant and microscopic

life, involves organic chemistry. In addition, many of the products we use every day (pharmaceuticals; plastics;

clothing; etc.) involve organic molecules. Organic chemistry holds a central place in chemical studies because

its fundamental principles and its applications touch virtually all other disciplines. Several years ago, a T-shirt

at an American Chemical Society meeting (in Dallas) sported the logo "Chemistry: The Science of Everything."

Organic chemistry is certainly an important player in that science.

Most Organic chemistry textbooks have a brief section to describe how Organic chemistry developed as a

science. I was a graduate student when I first read an Organic chemistry book that presented some historical

facts as part of the normal presentatin of facts. This was Louis Fieser's (USA; 1899-1979???) Advanced

Organic Chemistry book.1 This treatment gave perspective to my studies and helped me to better understand

many of the concepts. I believe that putting a subject into its proper context makes it easier to understand, so I

am introducing an abbreviated history of Organic chemistry as the beginning to this book. I will include

material from Fieser's book and also from an outstanding book on the history of Chemistry by Leicester.2 It is

important to remember the great Organic chemists of the past, not only to see how their work is used today but

to understand that it influences how we do chemistry.

1.1. A Brief History of Organic Chemistry

Humans have been using practical applications of chemsitry for thousands of years. The discovery and use

of folk medicines, the development of metallurigal techniques, and the use of natural dyes are simple examples.

For most of human history, humans were able to use chemcials without actually understanding the science

behind them. Organic chemistry became a defined science (the chemistry of carbon compounds) in the 19th

2

century, but organic compounds have been known and used for millennia. Plants have been "milked," cut,

boiled, and eaten for thousands of years as folk medicine remedies, particularly in Africa, China, India, and

South America. Modern science has determined that many of these

NH

HO

H

N

H3CO

H

1

OH

CH3

CH3

CH3

CH3 CH3

2

plants contain organic chemicals with effective medical uses, and indeed many of our modern medicines are

simply purified components of these plants or derivatives of them made by chemists. In one example, the bark

of Cinchona trees was

OH

O

O

H

OH

HO

HO

HO

OH

RO

O

3

O

CH34a R = H 4b R =

chewed for years to treat symptoms of malaria, for example, and it was later discovered that this bark contains

quinine (1), which is a modern medicine Ancient Egyptians ate roasted ox liver in the belief that it improved night

vision. Later it was discovered that ox liver is rich in Vitamin A (2), a chemical important for maintaining healthy

eyesight. An ancient antipyretic treatment (this means that it lowers a fever) involved chewing willow bark and it

3

was later discovered that this bark contained the glycoside salicin (3), a derivative of salicylic acid (4a).

Eventually, we learned how to make new organic molecules rather than simply isolating and using those that were

found nature. In the mid-19th Century a new compound was synthesized (chemically prepared from other

chemicals) called acetylsalicylic acid (4b), better known as aspirin, and it was found to be well tolerated by

patients as an effective analgesic (this means that it reduces some types of pain). These few examples are meant

to represent the thousands of folk medicine remedies that have led to important medical discoveries. All of these

involve organic compounds.

The symbols used (1-4) to represent the chemicals require some explanation. Each "line" is a chemical

bond. Therefore, C—C is a carbon-carbon bond and — is used as a shorthand notation to represent that bond.

Each "intersection of bonds" such as [ ] is a carbon atom. Various groups can be attached to these carbon

atoms (OH, NH2, CH3, etc.). The symbol C—N is a carbon-nitrogen bond, C—O is a carbon oxygen bond,

and O—H is an oxygen-hydrogen bond. These chemical structures will be explained in greater detail in

chapter 2.

Plants provided ancient humans with many organic chemicals or mixtures of chemicals that were useful for

purposes other than medicine. Ethyl alcohol (5) has been produced by fermentation of grains and fruits, and

H C

H

H

C

H

H

O

H

5

consumed for thousands of years in various forms. In ancient Bengal (part of

India), in Java, and in Guatemala, plants provided a deep blue substance used to

color clothing. In recent times, the main constituent was found to be indigo (6).

The ancient Phoenicians used an extract from a snail (Murex brandaris) found off

the coast of Tyre (now called Lebanon) to color cloth. It was beautiful and very expensive and the dye was

called Tyrian purple. It was so prized that Roman Emperors used it to color their clothing, and for many years

no one else was permitted to wear this color (hence the term "born to the purple"). The actual structure of the

organic chemical Tyrian purple is 7. Notice that the only difference between indigo and Tyrian purple is the

presence of two bromine atoms in the latter. Structural differences that on the surface appear to be minor can

lead to significant changes in the physical properties of organic compounds, such as color.

4

N

N

O

OH

H

N

N

O

OH

H

Br

Br

6 7

Organic chemicals have also been used in an unethical manner. The plant Belladona (Deadly Nightshade)

has been used for centuries as a poison. It was made famous by wealthy people in Medieval Europe who used

an extract of this plant to "do away" with rivals and enemies. The principle "poison" in this plant was found to

be atropine (8), which is also found in the stems of tomato plants (not the tomato itself).

These few examples show that organic chemicals have been important to humans for a very long time. For

most of this time, however, humans did not know the actual chemical structures of these compounds, or even

that they were dealing with discreet molecules. What they did know, however, was that a multitude of materials

could be obtained from natural sources, primarily from living organisms. In the following paragraphs, a few of

the chemists who advanced Organic chemistry as a science are introduced. This is certainly not an exhaustive

list but it "hits the high points."

N

H

O

O

OH

CH3••

8

As pointed out above, natural materials have been used for

many years. It was not until the 18th Century that people began

to look for specific chemicals in these natural materials. One of

the first to look for chemicals was Carl Wilhelm Scheele

(Sweden; 1742-1786), who isolated acidic components from

grapes and lemons by forming precipitates with calcium or lead

salts, and then adding mineral acids to obtain the actual

compounds. The compound from grapes is now known to be

tartaric acid (9) and that from lemon is now known to be citric

acid (10). Scheele also isolated uric acid (11) from urine.

5

HOOCCOOH

COOH

HO COOH

HOOC

OH

OH

9 10

N

N N

N

H

O

HH

O

H

O

11

O

HO

HO

N

CH3

H

HH

12

HO

CH3

CH3

H

H H

H3C

13

This practice of isolating specific compounds (now known to be organic compounds) from natural sources

was continued for many years (it continues today). Such compounds are called "natural products." Friedrich

W. Sertürner (Germany; 1783-1841), for example, isolated a compound from opium extracts in 1805. This is

now known to be morphine, 12. In 1815, Michel E. Chevreul (France; 1786-1889) was able to isolate a

crystalline material now known to be cholesterol (13) from animal tissues. In 1820, Pierre J. Pelletier (France;

1788-1842) and Joseph Caventou (France; 1795-1877) isolated a material they called an alkaloid (an alkali-like

base) now known to be strychnine (14). Alkaloids are a large group of diverse compounds that contain

nitrogen and are primarily found in plants. Although difficult to define because of their structrual diversity,

alkaloids are commonly assumed to be basic nitrogenous compounds of plant origin that are physiologically

active.

Clearly, an early step in Organic chemistry was to isolate pure compounds from natural sources and

6

N

O

N

O

H

H

HH

H

14

then attempt to identify them. Initially, the compounds were

purified (usually by crystallization) and characterized as to their

physical properties (melting point, boiling point, solubility in

water, etc.). It was not until much later (late 19th century and

early 20th century) that the structures of most of these

compounds were known absolutely. Justus Liebig (Germany;

1803-1873) perfected the science of organic analysis based on

the early work of Antoine Lavoisier. Late in the 18th Century,

Lavoisier (France; 1743-1794) made a monumental contribution to the science of chemistry that was critically

important to understanding organic chemistry. He first discovered that air was composed mainly of oxygen

(O2) and nitrogen (N2). He then burned natural materials in air and discovered that carbon in the material was

converted to carbon dioxide (CO2) and the hydrogen in these compounds was converted to water (HOH). By

trapping and weighing the carbon dioxide and the water, he was able to calculate the percentage of carbon and

hydrogen in molecules. Since we now know that organic molecules are composed mainly of carbon and

hydrogen, this elemental analysis procedure was, and is an invaluable tool for determining the structure of

organic molecules (see chapter 2, section ??).

In 1807, a Swedish chemist named Jöns J. von Berzelius (Sweden; 1779-1848) described the substances

obtained from living organisms as organic compounds, and he proposed that they were composed of only a

few selected elements, including carbon and hydrogen. Up to this point, all organic compounds had been

isolated as products of "life processes" from living organisms (hence the term organic). Early in the 19th

Century, Berzelius and Charles F Gerhardt (France; 1816-1856) described what was known as the vital force

theory that subscribed to the notion that "all organic compounds can arise with the operation of vital force

inherent to living cells." The vital force theory was widely believed at the time, but in 1828 Friedrich Wöhler

(Germany; 1800-1882)

N

H

H H

H

O C NH2N

O

NH2

HEAT

15 16

7

synthesized (prepared from other chemicals) the organic molecule urea (16, a component of urine and also a

major component of bird droppings which have been used for centuries as fertilizer from chemicals that had not

been obtained from living sources. When he heated ammonium cyanate (15), the product was urea (16). This

work, along with that of others, was contrary to the vital force theory because it showed that an organic

compound could be produced from a "non-living" system. However, it was not until Marcellin Berthelot

(France; 1827-1907) showed that all classes of organic compounds could be synthesized that the vital force

theory finally disappeared.

N

N

N

N

NH

H3C

H2NH2N

N

H

CH3

+

17 18

Synthesis of organic molecules began in the mid-19th Century and many compounds were prepared.

Hermann Kolbe (Germany; 1818-1884) prepared ethane (CH3CH3) by electrolysis of potassium acetate and

Sir Edward Frankland (England; 1825-1899) prepared butane (CH3CH2CH2CH3) from iodoethane

(CH3CH2I) and zinc (Zn). Charles A. Wurtz (France; 1817-1884) discovered amines in 1849 and August W.

von Hofmann (Germany/England; 1818-1892) prepared many amines as well as their ammonium salts.

Amines contain nitrogen in addition to carbon and hydrogen. At about the same time, Alexander W.

Williamson (England; 1824-1904) showed how ethers (ethers contain the C-O-C linkage) could be prepared

from the potassium salt of an alcohol (contains a C-O-H unit) and an alkyl iodide (contains a C-X bond, where

X is a halogen). The first secondary alcohol (a molecule with an OH attached to a carbon atom attached to two

other carbon atoms) was prepared by Charles Friedel (France; 1832-1899) in 1862 and the first tertiary alcohol

(a molecule with an OH attached to a carbon atom attached to three other carbon atoms) was prepared by

Alexander M. Butlerov (Russia; 1828-1886) in 1864. The nomenclature for this compound and all others will

be described in chapter 3.

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At about this same time (1863), William H. Perkin (England; 1838-1907) prepared the first commercially

useful synthetic dye (made by humans), mauve. He reacted pseudomauvein (17) and mauveine (18) and

obtained a dye with a purple color that had not been previously isolated from nature. In 1869, the synthesis of a

natural dye was reported by Carle Graebe (Germany; 1841-1927) and Carl Liebermann (Germany; 1882-

1914). They prepared the natural dye alizarin (20) from anthracene (19, obtained from petroleum distillates) by

the sequence shown. Adolf von Baeyer (Germany; 1835-1917) was the first to synthesize the dye indigoO

O

O

O

O

O

Br

Br

OH

OH

19

20

HNO3 Br2

KOH

(6). Aspirin (4) was first prepared in the mid-19th century and commercialized later in that century. The

synthesis of the various dyes and of aspirin were enormously important to the economies of both England and

Germany in the late 19th and early 20th centuries. Clearly, a major step in organic chemistry involved the

chemical synthesis of the compounds that could be isolated from nature, and then expanding this to prepare

compounds that were not known in nature. Once accomplished, these products were commercialized and this

led to the development of chemical industries.

H C

H

H

H H H

H

H

C ••

••

••••

21 22

By the middle of the 19th Century, chemists were

beginning to understand that organic molecules were discreet

entities and they were able to prepare them. Determining the

structures of these compounds (how the atoms are connected

together), however, posed many problems. The idea of valence was introduced by C.W. Wichelhaus (1842-

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1927) in 1868. Butlerov (see above) introduced the term "chemical structure" in 1861. There was no accepted

method to determine how atoms in a molecule were arranged in a molecular structure. In 1859, August Kekulé

(German; 1829-1896) "pushed" the idea of discrete valence bonds. It was actually Jacobus H. van't Hoff

(Netherlands; 1852-1911) and Joseph A. Le Bel (France; 1847-1930) who deduced that when carbon appeared

in organic compounds, it was connected to four other atoms and the shape of teh atoms around carbon was

tetrahedral. This means that carbon is joined to other elements by four chemicals bonds, as in 21 (methane),

where each line connecting the atoms represents a chemical bond (see chapter 2, section ?? for a full

explanation of these "lines"). In 1859, however, it was not really known how these four other atoms were

attached. The concept of a bond was vague and largely undefined. It was not until 1916 that Gilbert N. Lewis

(USA; 1875-1946) introduced the concept of a bond formed by sharing electrons. He called a bond composed

of shared electrons pairs a covalent bond. Erich Hückel (Germany; 1896-xxxx) developed theories of bonding

and orbitals and also speculated on the nature of the C=C unit, although it was Alexander Crum Brown

(England; 1838-1922) who first wrote a "double bond" for ethylene in 1864. It was Emil Erlenmeyer

(Germany; 1825-1909) who wrote acetylene with a triple bond (a C≡C unit) in 1862.

Understanding covalent bonds allows us to understand how organic molecules are put together. Returning

to methane, the four bonds to carbon could now be represented as 22, where each ":" represents two shared

electrons. A structure such as 22 is commonly known as a Lewis electron dot structure. In 1923, Lewis came

up with the idea that a molecule that accepts an electron pair should be called an acid and a molecule that

donates an electron pair should be called a base. These are called Lewis acids and Lewis bases to this day.

Clearly, understanding where electrons are in an organic molecule and how they are transferred is important in

understanding both the structure of molecules and also their chemical reactions. In 1925 two physicists, W.

Karl Heisenberg (Germany; 1901-1976) and Erwin Schrödinger (Austria; 1887-1961) described the orbital

concept of molecular structure. In other words, they introduced the idea of orbitals in chemistry and bonding

(see chapter 2). Today we combine these ideas by saying that orbitals contain electrons, and orbital interactions

control chemical reactions and explain chemical bonding. Clearly this area of organic chemistry involved

identifying the chemical structure of organic molecules and relating that structure to organizations of atoms held

together by shared electrons.

The spatial relationships of atoms and groups within these compounds are indicated by the solid and dashed

lines (indicating "up" or "down" respectively in the two-dimensional structure). This three-dimensional

10

orientation is called the stereochemistry of that atom or group. It was not until the middle and late 20th century

that the stereochemistry of these compounds could be accurately determined. This was a very important

development because the concept of sterochemistry is almost as old as organic chemistry itself.. In 1848, Louis

Pasteur (France; 1822-1895) found that tartaric acid existed in two forms that differed only in their ability to

rotate plane polarized light in different directions (they are examples of stereoisomers). Because of this

difference, the two forms of tartaric acid are considered to be different compounds. Van't Hoff found that

alkenes existed as a different type of stereoisomer. Pasteur, Van't Hoff and Le Bel are widely considered to be

the founders of stereochemistry. Emil Fischer (Germany; 1852-1919) studied carbohydrates in the late 19th

and early 20th centuries and made many major contributions not only to understanding their chemistry, but also

their structures and stereochemistry. Many scientists have helped develop this concept into the powerful tool it

is today, including John Cornforth (Austria/England; 1917-), Vladimir Prelog (Yugoslavia/Switzerland; 1906-),

and Donald J. Cram (USA; 1919-).

NH3C

H3C CH3

OH

CH3

O

23 24

Over the years, the molecules that could be synthesized have become increasingly complex. Apart from

simply synthesizing the molecules, this research also contributes to the development of new chemical reactions,

as well as new chemical reagents (molecules that induce a chemical transformation in another molecule). It is

useful to examine a handful of syntheses of organic molecules to show the structural challenges, and also how

more sophisticated methods and reagents might be necessary. The choice of the compounds prestend here is

largely due to the book3 by Elias J. Corey (USA; 1928-) who described the theory and practice of modern

organic synthesis. In 1904, William H. Perkin Jr. (England; 1860-1929) synthesized α-terpineol (23) and in

1917, Sir Robert Robinson (England; 1885-1975) synthesized tropinone (24). In 1929, Hans Fischer

(Germany; 1881-1945) synthesized protoporphyrin (hemin, 25) and quinine (1) was synthesized in 1944 by

11

Robert B. Woodward (USA; 1917-1979) and William von E Doering (USA; 1917-). Hemin contains the unit

found in hemoglobin, the oxygen-carrying component of blood, and quinine is an effective anti-malarial drug.

In 1951, Sir Robert Robinson and Robert B. Woodward synthesized strychnine (14), Gilbert Stork

(Belgium/USA; 1921-) synthesized cedrol (26) in 1955, Woodward synthesized reserpine (27) in 1956, and

Elias J. Corey synthesized helminthsporol (28) in 1963. Strychnine is a poisonous alkaloid that acts as an

analeptic (stimulates respiration—used in acute respiratory failure). Cedrol is an odoriferous component of

cedar wood oil, considered to be rare and valuable in ancient times. Reserpine has been used to treat

hypertension because it lowers high blood pressure and it also acts as a tranquilizer. Helminthsporol is a

natural plant-growth regulator isolated from Helminthospronium sativum. The structural complexity of these

molecules consistently increased

N

N

N

N

CH3

H3C

H3C

COOH

CH3

COOH

Fe

25

CH3

HOCH3

H

H3CCH3

26

12

N

N

H

H3COH

H

H

OCH3

O

O

OCH3

OCH3

OCH3

O

H3CO

27

H3C

H3CH

CH3O

H

H

CH3

OH

28

over the years. This trend continues with syntheses of organic molecules

reported today. Several molecules synthesized in the last few years

include taxol (29) by Robert Holton (USA; 1944-), avermectin B1a (30)

by Samuel Danishefsky (USA; 1936-), and naphthyridinomycin (31) by

David Evans (USA; 1941-). Taxol is a naturally occurring compound

used to treat cancer. Avermectin B1a is a natural product with potent

anthelmintic properties. It exerts its insecticidal activity by interfering with

invertebrate neurotransmission. Naphthyridinomycin is also a natural product that is a broad spectrum

antibiotic. There have been a huge number of syntheses reported in the last fifty years that have contributed

enormously to Organic chemistry. Notice that the stereochemistry of these molecules is included. Preparing

compounds with only that particular arrangement of atoms and groups can be most challenging. There is no

question that another area of organic chemistry has involved developing chemical reactions to the point that

virtually any molecule can be prepared. Understanding chemical reactions, the reagents used in those reactions,

and the developing new reagents and reactions is a critical part of the synthesis of organic molecules (including

those shown here), and this has profound influences in all areas of organic chemistry.

Prior to the late 1940's and 1950's, chemists did not really understand how chemical reactions occurred. in

other words, what happened during the bond making and bond breaking process. Understanding these

processes, now called reaction mechanisms, required an enormous amount of work in the period of the late

1940's throughout the 1960's, and it continues today. The pioneers in this area include Frans Sondheimer

(Germany; 1926-), Saul Winstein (Canada/USA; 1912-), Sir Christopher. K. Ingold (England; 1893-), John

13

O

H3C O

O

O

CH3OH

O

H

O

H

O

N

O

H OH

O

O

CH3

O

CH3

HO

29

D. Roberts (USA; 1918-), Donald J. Cram (USA; 1919-), Herbert C. Brown (England/USA; 1912-), George

A. Olah (Hungary/USA; 1927-), and many others. They first studied reactions that were ionic in nature and

identified many types of reactive ionic intermediates such as carbocations or carbanions, and another type of

intermediate called carbon radicals. An intermediate is a transient and usually high energy molecule that is

formed initially and then transformed into a final, and more stable product. The nature and structure of these

intermediates were determined, and methods were developed to ascertain the presence of these intermediates and

also how long they were present in the reaction (in other words, how reactive they were). The idea of reaction

kinetics was developed so that it

14

CH3

O

OO

O

H

OH

O

O

H3C

H

CH3

OH

CH3

OO

OH

HH3C

H3CO

H3CO

HO

H3C

CH3

30

could be determined how fast products were formed and reactants disappeared. This information gave clues as

to how the reaction proceeded and what, if any, intermediates were involved. Roald Hoffman (Poland/USA;

1937-) and Kenichi Fukui (Japan; 1918-), along with Robert Woodward (USA; 1919-1970), described the

N

N

N

O

O

O

H3CO

H3C CH3

H

H

H

H

OH

OH

31

concept of frontier molecular orbitals and the use of orbital symmetry to explain many reactions that did not

appear to proceed by ionic intermediates. The concept of reaction mechanism allows a fundamental

understanding of how organic reactions work and it is a relative late-comer to the study of Organic chemistry.

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It is perhaps the most important aspect however, because understanding the mechanism of chemical reactions

allows chemists to predict products and reaction conditions without having to memorize everything.

Finally, how does a chemist know the structure of any organic chemical? How are organic

chemicals isolated? In early work, inorganic materials such as metal salts and acids or bases were added to

force precipitation of organic compounds. In other cases, liquids were distilled out of "organic material" or

solids were crystallized out. In the 1950's, the concept of chromatography was developed by A.J.P. Martin

(USA; 1910-) and Richard Synge (England; 1914-) and this allowed chemists to conveniently separate

mixtures of organic compounds into individual components. Light has always been an important player in

chemistry. In the early-mid 20th Century, ultraviolet light was shown to interact with organic molecules at

certain wavelengths. In the 1940's and 1950's, molecules were exposed to infra-red light, and again molecules

absorbed certain wavelengths. Identification of which wavelengths of light were absorbed and correlating this

with structure was a major step in the identification of organic molecules. Even today, ultraviolet spectroscopy

and infrared spectroscopy are major tools for the identification of organic compounds. In the 1950's and

especially in the 1960's, it was discovered that organic molecules interacted with electromagnetic radiation with

wavelengths in the radio signal range, if the molecules were suspended in strong magnetic fields. Initially, it

was discovered that hydrogen atoms interacted in this manner and chemical differences could often be

discerned. If the different hydrogen atoms in an organic molecule could be identified, the chemical structure

could be puzzled together, giving a major boost to the identification of organic compounds. This technique is

now known as nuclear magnetic resonance spectroscopy (NMR) and is one of the most essential tools for an

organic chemist. With the power of modern computers we can now use NMR to determine the number and

type of carbon atoms, nitrogen atoms, fluorine atoms, lithium atoms, and many more in an organic molecule.

To do this, we use stable natural isotopes of these atoms; 13C, 15N, 19F, 6Li, etc. It is noteworthy that the

important modern tool of medicine (MRI or magnetic resonance imaging) is in reality an NMR technique

applied to medicine and it was developed in the 1970's. In the 1950's and especially in the 1960's and 1970's, it

was discovered that bombarding an organic molecule with a high energy electron beam induced fragmentation

of that molecule and identifying these fragments gave important structural formation. This technique is known

as mass spectrometry. Other tools are constantly being developed and each of the techniques mentioned has

"cutting edge" methodology that allows a chemist to probe very complex structures. This is typified by the use

of x-ray technology, known for many years, to identify crystalline molecules. When the x-rays interact with a

16

molecule with a distinct crystal structure, the x-ray scattering patterns can often be analyzed to provide clues to

its chemical structure. With modern computer technology, a picture of the structural features of a molecule can

be produced. With modern electron tunneling microscopes, pictures of atoms have been made. This aspect of

organic chemistry is vital and on-going. Using these techniques to give more information, and developing new

techniques is another major area of organic chemistry.

32 33

HO

N

O

O H

HH

O

N

H

HO

OH

HO

N

O

NH2

1.2 The Variety and Beauty of Organic Molecules

Section 1.1 described how organic chemistry came to be a science. Why is it important? You are alive

because of chemical reactions involving organic molecules. Your DNA and the proteins in your body are

organic molecules. Proteins are large structures composed of individual amino acids such as serine (32) and

DNA is made up of individual units called nucleotides such as cytosine, 33. If you are blinking an eye while

reading, or moving your arm to turn the page, that nerve impulse from your brain was induced by one of several

important organic molecules called neurotransmitters. One important neurotransmitter is acetylcholine

CH3

CH3

CH3

CH3 CH3

34 35

H3C

N

O

CH3

CH3

OCH3

OH

17

(34). If you see this page, the light is interacting with a photopigment in your eye called rhodopsin, which

releases retinal (35) upon exposure to the light. Retinal reacts with a lysine fragment (another amino acid) of a

protein as part of the process we call vision. Note the similarity of retinal to Vitamin A (2), which is simply the

reduced form of 35. What you see, at least the color associated with what you see, is usually due to one or

more organic molecules. If the trees and grass in your yard appear green, one of the chemicals responsible is

called chlorophyll a, 36. The ------ in 36 means the N is coordinated to Mg rather than formally bonded to it.

There are many other things about human physiology that involve organic

N

N

N

N

CH3

H3C

H3C CH3

Mg

36

O

O

phytl-OO

OCH3

OOH

37

HO O

CH3 OH CH3OH

CH3 HH

H H H H

38 39

chemistry. A silly one involves the odor that is noticeable if your feet have not been washed recently. They are

exuding a chemical called butyric acid (37), among other things, with obvious social effects. There are more

18

fundamental physiological influences of organic chemicals. If you are female, one of the principle sex

hormones for your gender is β-estradiol (38) but if you are male, your principle sex hormone is testosterone

(39). It should be noted that each sex has both of these hormones (and others), but in quite different amounts.

Notice that the chemical structures of estradiol and testosterone are somewhat similar.

Smells are a very important part of life. What are smells anyway? They are the interaction of organic

chemicals with olfactory receptors in your nose. If you walk into a garden and smell a rose, a chemical called

geraniol (40) is interacting with those olfactory receptors. If your dog or cat has ever been sprayed by aOH

H3C

CH3

CH3

40

skunk, many organic chemicals are part of the spray, including the

mercaptan 41. Clearly, this is an unpleasant smelling organic chemical

and your animal was very unhappy. If you are wearing musk cologne,

you are probably wearing 42 (muscone) if it is natural musk (scraped

from the hind-quarters of a male musk deer). If you are wearing a

jasmine perfume, it probably contains jasmone (43), which is part of the

essential oil of jasmine flowers. These are clearly more pleasant smelling organic molecules.

41 42 43

SH

CH3H3C

O

CH3

O

CH3

CH3

44 45

O

19

Many things around you involve subtle uses of organic molecules. If you see a housefly, know that they

use a chemical called a pheromone (in this case muscalure, 44) in order to attract a mate and reproduce. The

American cockroach (hopefully there are none in your dorm) similarly attracts a mate by exuding 45. To

control insect pests, we sometimes use the pheromone of an insect pest to attract it to a trap. Previously, we

have sprayed insecticides such as DDT (46) or PCB(47) directly on plants, often with

46 47

CCl3

Cl

Cl

Cl

Cl Cl

Cl

devastating environmental consequences. Nonetheless, without pest control and plant growth promoters, we

probably could not feed our enormous population. Understanding these chemicals, how they work and when to

use them is obviously important and requires a thorough understanding of organic chemistry. It is also

important to be able to develop new and environmentally safer compounds.

48 49

O

HO

OH

OH OH

OHH

H

H

H2N

O

N

H

O

OCH3

OOH

20

50 51

CH3

H3C CH3

CH3

H3CO

HO

N

H

O

H3C

CH3

Eating is obviously an important part of life, and the taste of the food is important. What are tastes? They

are the interaction of organic chemicals (and other chemicals as well) with receptors on your tongue. Are you

drinking a soda? Does it taste sweet? If it is not a diet soda, it probably contains a sugar called fructose

(48), but if it is a diet drink it probably contains the "sugar substitute" aspartame, 49. Different chemicals in

different foods have their own unique tastes. Do you like the taste of ginger? The active ingredient that

gives ginger its "spicy" taste is an organic molecule called zingiberene (50). Do you like the taste of red

chili peppers? If so, the "hot" taste is due to an organic chemical called capsaicin, 51. In both cases, these

chemicals interact with your taste buds to produce that characteristic taste. Capsaicin is also used in some

cremes used to alleviate symptoms of arthritis and muscular aches.

52 53

HO

N

H

O

CH3

H2N

O

O

NH

Cl

Most medicines used today are organic chemicals. Clearly, this is of vital importance to the health and well-

being of humans. Do you have a headache after reading all of this stuff? If so, you are probably looking

for a bottle of aspirin (4) or Tylenol (which contains acetaminophen, 52). Have you been to the dentist

recently? If so, you might have had a shot of Novocain (53, the actual name of this chemical is procaine

hydrochloride) so you would not feel the pain (it is a local anesthetic). If you have recently been ill,

21

54 55

N

S

O

CH3

CH3N

HH

OOH

H

O

H2N

OH

N

S

O

CH3

CH3N

HH

OOH

H

O

you might have received a prescription for an antibiotic from your physician. Commonly prescribed antibiotics

could include amoxicillin (54) or penicillin G (55), or even a tetracycline antibiotic such as aureomycin (56).

56

OH O OHOH

O

OH

NH3C

CH3

O

NH2

HO CH3Cl

There are clearly much more serious and devastating diseases that afflict humans. Has a friend or relative

been treated for cancer? The physician might have used vinblastine (57) or taxol (29) to treat the cancer. Do

you smoke? If so, you are breathing nicotine (58) as well as many other organic compounds into your lungs.

Have you heard of the use of AZT for the treatment of AIDS? The structure of AZT is 59.

22

57

N

N

CH3

H3CO

N

N

H

H OH

O

OH

H

O

OCH3

O

CH3

O

OCH3

H

Finally, there are organic molecules that touch vast areas of your life, often in subtle ways. When I say they

touch you, I mean that quite literally. Are you wearing clothes? If so, you might be wearing a synthetic

blend of cloth made from rayon (cellulose acetate, 60). This is a polymer (a large molecule made by bonding

many individual units together). The "n" beside the bracket represents the number of repeating units (this is

common nomenclature for all polymers). You might be wearing something made from Nylon 66,

58 59

N

N

CH3 O

HO

N3

N

N

O

H

O

CH3

H

whose chemical structure is 61. Have you ever heard of Teflon? It finds uses in many machines and devices

that you use every day. It has the structure shown for 62 and natural rubber is polyisoprene (63). You might

be using a piece of paper to describe your thoughts about organic chemistry at this moment. If so, you are

writing on something with cellulose (64) in it. Notice that rayon is simply a derivative of cellulose, the main

23

constituent of wood fiber. When you crumple up the paper and throw it into a "plastic" waste container, that

container might be made of polyethylene, 65.

60 61

OO

O

O

OH3C

OO CH3

OCH3

n

N

H

O N

H

O

O

N

H

n

62 63

F F

F F

H3C

n

n

I have thrown a lot of structures at you. Why? I am trying to convince you that organic chemistry is all

around you and an integral part of your life. Understanding these things can help you make informed choices.

Virtually every aspect of our life is touched by an organic molecule, every day of our lives. This is why you are

sitting there reading this book. I hope that understanding the concepts in its pages will not only help you in

your career, but also help you to understand the beauty that surrounds you. It might also help you understand

the dangers that surround you in the form of organic molecules; pollution, illicit drugs, chemical weapons. I

hope that understanding organic chemistry will help you to understand some of the debate that swirls around

these subjects. Good luck!

64 65

O

HOHO

O

OHC

C

H H

H Hnn

24

ReferencesReferences

1 Fieser, L.F.; Fieser,. M. Advanced Organic Chemistry, Reinhold, New York, 1961; pp. 1-31.

2 Leicester, H.M.; The Historical Background of Chemistry, Wiley, New York, 1956, pp. 172-188.

3 Corey, E.J.; Cheng, X-M. The Logic of Chemical Synthesis, Wiley, New York, 1989.