Organic Chemistry
A Linear Text
Chapter 1
Introduction
Concepts:
* A definition;
* A basic chemical reaction and symbolism,
* Reasons for study of organic chemistry
* Importance to modern society and to YOU.
* The future?
What is organic chemistry?
Organic chemistry is a study of the compounds of CARBON. "Compounds" are composed of many, many molecules, which, in turn, are composed of two or more atoms, the fundamental building block of nature. In organic chemistry, the most frequently encountered types of atoms are carbon (chemical symbol, C), hydrogen (H), oxygen (O) and nitrogen (N). A huge number of organic compounds exist because of the ability of carbon to form a chemical bond to another atom, usually another carbon.
The term "compound" stems from the middle ages. Then as now, chemistry was deeply allied with the health professions. For a time, the formulation of pharmaceuticals (ethical drugs, such as your doctor would prescribe) was termed iatrochemistry. In the middle ages, apothecaries (the pharmacists of that age) would provide "simples", composed of just one substance, or "compounds", which were composed of two or more substances, to attempt to cure ailments.
In later years, organic chemistry evolved to the study of compounds found in nature. Around 1800, it was divided into "plant chemistry" and "animal chemistry". Today, studies on chemicals found in living systems have become biochemistry, an entirely separate field of study.
At one time (the1700's), the "Vitalism Theory" held that organic compounds could only be derived from living systems, i.e. plants or animals. It was not considered possible to attain organic chemicals from inorganic sources, such as minerals, which never "lived".
This idea was dispelled when Wohler (Riga, 1828) heated the inorganic salt "ammonium cyanate" and obtained "urea". Urea, of course, is a constituent of urine. Urea itself is odorless and it is colorless and crystalline.
In the above chemical equation, NH4+ is "ammonium", and -OCN is "cyanate". The arrow signifies a chemical reaction that occurs under the influence of heat to form another substance, that is, the molecule "urea". The Greek letter delta, shown over the arrow, is the symbol for "heat". In "urea", covalent bonds, which link atoms one to another, are signified by lines. The atoms of organic compounds are "held together" by covalent bonds. Covalent bonds will be discussed in more detail later. When you see an equation such as this, the materials to the left (ammonium cyanate) are termed: "starting materials", or sometimes, "reactants", or "reagents". The material to the right (urea), is termed the "product" of reaction. Secondary products, of lesser importance, termed "side products" are sometimes also shown, sometimes not. Often, the "solvent" in which the reaction is done is shown beneath the arrow. This particular reaction is highly unusual in that it has no solvent. Other reagents may be shown over the arrow. You will run into this type of symbolism time and again, and so these conventions must be remembered. Reactions of this type, usually much more complicated, are termed "syntheses". A "synthesis" involves the "preparation of" or the "making of" a desired product. Organic chemistry is deeply involved in chemical reactions, unlike some other areas of chemistry.
Today, many millions of organic chemicals exist. Some texts place the number over twenty million. Almost all are man-made, that is, they have been "synthesized" in the laboratory. Others come from nature. Today, the study of organic chemicals found in nature is termed "natural products". They are obtained by "isolation" from natural sources", not by synthesis. "Isolation" signifies the process of separation of a desired chemical from other chemicals present. The object of an isolation is to obtain a single, pure substance. This is not an easy task, as plants or animals have 1000's of compounds present.
The number of new organic chemicals, never before made or "synthesized", is increasing approximately 1000 per week. Organic chemistry, thus, is an extremely large science, that is actively pursued around the world.
Why study organic chemistry?
Organic chemistry has had a huge impact on life, past, present and most likely for the future. For example, the twenty medicines most actively prescribed by doctors are ALL organic chemicals. Some of hese are shown at the end of this chapter. These compounds are synthesized by chemical reactions very similar to what you will explore in the lab portion of this course. The preparation of these medicines is done by organic chemists and chemical engineers, and the dosage was worked out by pharmacologists.
Areas of modern life influenced by organic chemistry include the following:
* pharmaceuticals
* polymers
* plastics
* elastomers (rubbery materials)
* fibers (e.g. Nylon, Dacron, Orlon)
* dyes and pigments
* chemicals for food preparation or preservation
* agricultural chemicals
* pesticides
* herbicides
* industrial chemicals, e.g. components of brake fluid, solvents for finger nail polish, propellants for paint cans (formerly), detergents, caulkings for houses, and thousands of others.
[An interesting account of the use of chemicals in personal care products comes from the Rohm and Haas Co.: http://www.rhpersonalcare.com/].
The ultimate source of the above organic chemicals is petroleum. A very few come from coal or from ethanol derived from corn. When petroleum is high priced, the above chemicals will go up in price as well.
Some stories:
A. For 1000's of years, purple cloth was worn only by the monarchs of Europe and the mid-east. "Royal purple" was associated with high station. Only kings and emperors could afford this dye, also called, "Tyrian purple". The dye was named for the city of Tyre in present day Lebanon. Its source was the rare Murex species of mollusc found in the Mediterannean Sea. This was an early instance of "isolation" of a natural product. It is said that it takes about 10000 molluscs to provide 1 g of Tyrian purple dye. Around 1880, a chemical synthesis was worked out for Tyrian purple and also for the closely related related dye, "indigo", The price plummeted when the European chemical industry began to turn out these dyes in large quantity. In fact, indigo became the dye for blue jeans. Indigo is not a particularly good dye, as it is not "washfast". Washing the garment washes out the dye, and the blue color fades. Today, jeans are washed at the factory, giving them their characteristic faded blue appearance. Up to about 1950, new blue jeans were just that, a deep blue.
At this stage, do not attempt to fully understand chemical structures such as that of "Tyrian purple" or "indigo". The important aspect is that they are organic chemicals composed of carbon, hydrogen, nitrogen, oxygen, and in the case of Tyrian purple, of bromine. In the above chemical structures, a carbon exists at each break of a line. Hydrogens are not shown. Two lines signify a "double (covalent) bond", i.e. two covalent bonds.
B. In an early form of agricultural protectionism (1700's and 1800's), the dye "Alizirin" was adopted for use with British military uniforms, and it became "de riguer" for fox hunting garments as well. British soldiers became known as the "red-coats". This provided steady income for British farmers, who grew the "madder root" from which Alizirin could be isolated.. About 1870, German scientists worked out a chemical synthesis for Alizirin, which provided the dye at much smaller cost. Another advent, "smokeless powder" (from Alfred Nobel and others), made the atmosphere around battlefields much clearer. It became easier to discern one side from the other. The unfortunate color, which made British soldiers easy targets, was dropped. The consequences in the agricultural sector were said to be quite severe.
The first commercial successes in organic chemistry were from dyestuffs. One synthetic dye "mauve" provided a shade that became so popular that it altered the fashion industry of the time, and ushered in the "mauve decade" in the late 1800's.
B. After Pearl Harbor in 1941, Japan quickly seized the Malay peninsula, the Phillipines, and the East Indies (present day Indonesia). There was some danger that the US would be out-of-the-war as soon as it started, as Japan controlled all major sources of natural rubber. Only minor quantities were available to the US from South America. Planes, trucks, jeeps, etc. would have had to run on steel wheels, as rubber tires and tubes would have soon become unavailable. The US was prepared and the chemical industry was able to move fairly rapidly to the formulation of "synthetic rubber" from two industrial chemicals "styrene" and "butadiene". The following equation shows the "bare-bones" of the synthesis of a huge molecule called a "polymer". You need not understand its details now. The structure is too large to present in its entirety. The "squiggles" in the chemical structure mean "more-of-the-same" past this point. Once again, each break in the line represents a carbon plus hydrogens.
C. "Sulfa drugs" were the first successful antibiotics. Their origin arose in an interesting manner. Although high school science courses are imbued with the "scientific method", the origin of sulfa drugs came about essentially from an inverse process: a "technique" in search of a "problem".
In the1800's and early 1900's, microscopes became fairly widespread. Biologists had difficulty in viewing microorganisms such as bacteria under the microscope, since the microorganisms were colorless and not differentiated from the background.. Scientists then tried to "stain" bacteria with some of the new organic dyes that had become available. One can almost hear the scientists at I.G. Farbenindustrie in Germany thinking: "We have an interesting way of looking at bacteria, using these dyes. I wonder if one of these dyes would not only stain the bacteria, but kill the bacteria. We could see that as well. That substance might be useful as a drug." One of 1000's of dyes that were tested was "Prontosil". The "azo function" (N=N) in this dye is responsible for its color. It is termed a "chromophore". Azo compounds are usually orange to red in color. Biologists found that bacteria treated with Prontosil not only became visible under the microscope, but they apparently had been killed. But, was it useful as a medicine to combat bacterial infections in humans?. There might be toxicity problems. In this case, it indeed appeared to control bacteria and it was not too toxic to humans.
Some very nice, early research by a French firm showed that the colored nature of Prontosil had nothing to do with its bacteriocidal activity. Prontosil was converted "in vivo" (by enzymes in the body) to "Sulfanilamide", which was the actual bacteriocidal agent. Sulfanilamide was the "starting material" for synthesis of Prontosil. Sulfanilamide, one of the first sulfa drugs, is quite insoluble. Much research was devoted to finding more soluble compounds, e.g. "Sulfapyridine" and "Sulfathiazole", among others. These compounds could then dissolve in the gastric juices of the stomach or intestine, pass into the blood, and be delivered by the blood to the diseased organs. The common practice is to place oxygens and nitrogens in the basic chemical structure to improve solubility in water, while, hopefully, keeping human toxicity to a minimum.
["In vitro" is the opposite of "in vivo". "In vitro", literally means "in-glass", e.g. tests in a Petri dish, whereas "in vivo" refers to tests in a living body. Today, "in vivo" tests are first conducted on test animals, say guinea pigs, but in the early days, human subjects were tested directly.]
In WWII, sulfa drugs saved many lives. The "sulfa drugs" were "dusted" onto wounds to prevent bacterial infection and gangrene, which had been a terrible problem in WWI. Sulfa drugs were replaced by the penicillins, after WWII, but since penicillins are no longer useful as antibiotics, sulfa drugs may regain a measure of interest.
D. For a fascinating account of industrial research, see the DuPont Company website: http://www.dupont.com/corp/science/index.html (go to "discontinuous innovation -- how it really works"). This account tells of the discovery of an "ionomer" later marketed by DuPont as "Surlyn". For many years, "Surlyn" was not at all economically successful. It was used only for the heels of ladies shoes in the U.K. and for golf ball coatings in this country. In the present day business climate, where each manager must show a profit each quarter, this product would almost certainly have been canceled. Yet, DuPont stood by this interesting, but difficult to formulate polymer. The DuPont website provides an account of how this material was too-good-of-an-adhesive that froze industrial equipment. Eventually, they learned how to handle this difficult material, new applications were found, and it grew to a $200 million per year business.
E. For a interesting account of Alzheimer's disease and also mad cow disease, go to the following website from Axonyx Corp: http://www.axonyx.com/
This website provides an account of the inception and spread of both diseases and the use of small organic molecules to inhibit the spread of the disease and to preserve cognitive functions in the case of Alzheimer's:
The future?
* Materials Science. The combination of chemistry, physics and engineering will be a powerful force in society.
* "Composites" will see further growth. The combination of graphite fibers with an organic polymer to form golf clubs and tennis rackets, but also the airframe for "stealth" aircraft will find many new applications.
* "Nanotechnology": The formulation of extremely small gears, "machines", etc. will almost certainly involve organic polymers.
* Will "organic semiconductors" replace silicon based or gallium-arsenide semiconductors? Probably not, although organic semiconductors should find increasing use.
* "Organic magnets" will see the light-of-day.
* "Biodegradable polymers:" This subject has proven to be a tough problem. The future should see some breakthroughs.
* Polymer display devices: Electroactive polymers -- formulated to be almost as thin and flexible as a piece of paper -- will become common. Refrigerators, cars and many other everyday objects should have small computer "screens". These displays are brighter than "liquid crystal displays", and color is possible. All of the above applications will involve organic chemistry and its sister science, polymer chemistry.
* "Graphite" golf clubs, airplane wings, automotive panels, etc.,The matrix for the graphite is an organic polymer.
* Applications to the Health Sciences: The combination of genomics, proteomics and organic chemistry should be a powerful force in the discovery of new pharmaceuticals. For the first time, "directed" design of pharmaceuticals is possible. This involves the synthesis of organic compounds based on strong clues from genomics as to what types of structures should be effective. The opposite is "shotgun" research (see below).
* "Combinatorial chemistry": This may involve "chemistry-on-a-chip" as well as other methods. "Combichem" is the utlimate in "shotgun" research. Researchers will be able to synthesize huge numbers of organic compounds in small quantities by automated methods. Those few which show "activity" against disease will be pursued further.
* "Microfluidics", involves very small reaction "vessels".
At the same time, good, old-fashioned organic chemistry should remain strong in formulating compounds for the improvement of consumer goods, housing materials, aviation, food, and many other applications.
Should I be afraid of organic chemicals in laboratory?
The media have sensitized people to the dangers of chemicals. Remember that the media must maximize the number of readers or viewers in order to please advertizers. Sensationalized accounts of dangers to the populace in spills of "hazardous" chemicals are all too common. One of the objectives of your study of organic chemistry will be to attain some sophistication in judging these media accounts. Unhappily, much of the populace, including media writers themselves, are "scientifically illiterate", or else they "turn off" their education in science.
Toxicologists have a saying: "The dose makes the poison." This means that if you ingest or breath chemicals past a certain level, then they indeed become detrimental to health. Even vitamins A and D become toxic at high dose levels. Most texts differentiate between "acute" and "chronic" effects. An "acute" exposure might be a one-time exposure to a high level of a chemical. A "chronic" exposure might be continuous exposure to a low-level of the chemical in question over a period of time. Remember that even sodium chloride -- table salt -- is officially classified as "toxic" on an acute basis. If you eat a huge quantity of sodium chloride, it will be fatal. However, the small quantities we consume with food are not dangerous.
Most scientists would modify the title to read: "Should I respect organic chemicals?" The answer is most certainly "yes". Students should practice neatness in the lab, as in their daily lives. Unnecessary exposure to organic chemicals should be avoided. However, abject "fear" is unwarranted at the low levels students will encounter most chemicals.
How can you tell at what levels a certain chemical becomes dangerous? This involves a assignment for you. Do a web search for "MSDS" sheets. "MSDS" stands for "Materials Safety Data Sheets". Then download a MSDS sheet for a chemical of your choice. A huge amount of information will be provided. Items of interest will include "LD50" and "TLV" or "PEL". "LD50" stands for "lethal dose" for 50% of test animals, i.e. at what dose level will 50% of test animals die? Since it is easier to kill a mouse than an elephant, "LD50" data are reported on a "per kilogram of body weight". Since the average human being weighs about 50 kg, calculate the amount of chemical which, if inhaled or ingested, would lead to a 50% chance of death. Unfortunately, all mammals are not the same. Test animals are usually rats or mice (and even they are different), never humans.
Murder mysteries often portray an unsuspecting victim being poisoned with arsenic by the villain. A member of the class should download the MSDS sheet for arsenic. How much arsenic would a 50 kg human being have to ingest to have a 50% chance of death? The amount of arsenic may surprise you.
"TLV" (threshold limit values) data show the level above which airborne contaminants become a health problem. These are provided as "ppm" (parts per million) or "mg/m3" (milligrams of the substance in question per cubic meter of air). Unfortunately, these will be somewhat difficult for you to evaluate. First, calculate the number of cubic feet present in your classroom. Convert this number to cubic meters by mutliplying by 0.02832.
Let's take "acetone", a common, laboratory solvent, as an example. The TLV for acetone is given as 2400 mg/m3, or 1000 ppm. Knowing the volume in cubic meters of your classroom, which you calculated, now calculate the total amount of acetone that would have to be present in your lab's atmosphere to meet the TLV of 2400 mg/m3 limit. Let's further suppose that each member of the class in turn leaves the acetone container open for 1 minute, and 0.8 g. of acetone evaporates into the air during this period in which the container is open to the air. The total weight of acetone dispersed in your classroom then would be x * 0.8, where x is the number of students in your class. Divide by the volume of your lab in cubic meters. Report to the teacher whether or not you have an air contamination problem for acetone, given the above variables.
[Note: 1 mL of acetone vapor (not liquid) dispersed in 1,000,000 mL (1000 L) of air would represent 1 part per million (ppm) of acetone in air. As a very rough guideline, the human nose can detect common solvents such as acetone or ethyl acetate as low as about 2-4 ppm, depending upon the person. Remember, the TLV for acetone is 1000 ppm.]
Now do the same for "bromine", a much more toxic substance.
"TLV" data are also available in the "Handbook of Chemistry and Physics". Look under "Threshold Limits -- Air Contaminants" in the index.
"PEL" values are "permitted exposure limits". These are acute air contamination limits. These are quoted on an "acute" and on a "chronic" basis. For example, the OSHA has established a PEL of 5 ppm for "vinyl chloride", a serious "carcinogen" (causes cancer), for no more than 15 minutes exposure. The TLV is 0.5 ppm (averaged over an eight hour work-day).
Question: Why do you suppose that "vinyl" upholstery, garden hose, etc. must be carefully "degassed"? "Vinyl" also goes by the name of "PVC" (poly vinyl chloride)?
Eight of the Twenty Most Heavily Prescibed Pharmaceuticals (1996)
The remaining twelve of the twenty are likewise organic chemicals (cf. A.W. Czarnik, Accounts of Chemical Research, 1996, 29, 111)
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