CHEMICAL NAME = 4-(2-aminoethyl) benzene-1,2-diol
3-(3,4-Dihydroxyphenyl)-L-alanine (L-Dopa)
CAS NUMBER = 51–61–6 59–92–7 (L-Dopa) MOLECULAR FORMULA = C8H11NO2 C9H11NO4 (L-Dopa) MOLAR MASS = 153.2 g/mol 197.2 (L-Dopa) COMPOSITION = C(62.7%) O(20.9%)
H(7.2%) N(9.1%)
C(54.8%) O(32.5%) H(5.6%) N(7.1%) (L-Dopa)
MELTING POINT = 128°C 295°C (L-Dopa) BOILING POINT = decomposes
DENSITY (CALCULATED) = 1.25 g/cm3 1.47 g/cm3 (L-Dopa)
Dopamine, abbreviated DA, is a biosynthetic compound and neurotransmitter produced in the body from the amino acid tyrosine by several pathways. It is synthesized in the adrenal gland where it is a precursor to other hormones (see Epinephrine) and in several portions of the brain, principally the substantia nigra and hypothalamus. Dopamine is stored in vesicles in the brain’s presynaptic nerve terminals. It is closely associated with its immediate precur-sor, l-Dopa (levodopa). Casmir Funk (1884–1967) fi rst synthesized Dopa in racemic form
106 | Th e 100 Most Important Chemical Compounds
in 1911 and considered Dopa a vitamin. In 1913, Marcus Guggenheim, a biochemist from Hoff man-LaRoche, isolated l-Dopa from seedlings of Vicia faba, the Windsor bean plant native to northern Africa and southwest Asia. Guggenheim used beans from the garden of Felix Hoff man (1868–1946), the discoverer of aspirin. Guggenheim ingested a 2.5-gram dose of l-Dopa, resulting in nausea and vomiting; he also administered small dosages to animals and did not observe any signifi cant eff ects. Th is led him to believe that l-Dopa was bio-logically inactive. Studies commencing in 1927 reported that Dopa played a role in glucose metabolism and aff ected arterial blood pressure. Interest in dopamine accelerated in 1938 when the German physician and pharmacologist Peter Holtz (1902–1970) and co-workers discovered the enzyme l-Dopa decarboxylase and that it converted l-Dopa into dopamine in humans and animals. Research over the next two decades focused on l-Dopa’s role as a precur-sor to other catecholamine hormones, its vascular eff ects, and its role in brain chemistry.
One large area of dopamine research involves its role in Parkinson’s disease. Parkinson’s dis-ease is a progressive neurological disorder resulting from the degeneration of neurons in regions of the brain that control movement. Symptoms include tremors in the limbs, slow movement, shuffl ing gait, rigidity in the limbs, and stooped posture. Parkinson’s disease is associated with a shortage of dopamine leading to impaired coordination of movement. Parkinson’s disease was fi rst described in An Essay on the Shaking Palsy, published in 1817 by a London physician named James Parkinson (1755–1824). Parkinson’s disease has probably existed for thousands of years; its symptoms and suggested treatments appear in ancient medical texts.
A signifi cant medical breakthrough involving dopamine and l-Dopa occurred around 1960 when it was demonstrated that Dopa could be used to treat Parkinson’s disease. In the previ-ous decade, Arvid Carlsson (1923–) demonstrated that dopamine played a direct role in brain chemistry as a neurotransmitter. In a 1957 article, he reported on how he was able to reverse the eff ects Parkinson-like eff ects in reserpinized animals by administering l-Dopa. Reserpine is an alkaloid compound that causes depletion of neurotransmitters such as dopamine when administered to animals. Carlsson received the 2005 Nobel Prize in physiology or medicine for his work on dopamine’s role as a neurotransmitter. Another study in 1960 involving autopsies on individuals with Parkinson’s disease showed that the subjects had extremely low dopamine levels in the brain. Studies in the 1960s established the use of dopamine in treating Parkinson’s patients. One of the problems with using dopamine was that it did not penetrate the blood-brain barrier. To overcome this problem, the precursor Dopa, which did pass the blood-blood-brain barrier, could be used, although injected Dopa was toxic. Clinical trials produced progress, but it was not until 1967 that George C. Cotzias (1918–1977) showed that, by starting with small oral doses that were progressively increased over time, remission of Parkinson’s symptoms occurred. Cotzias also found that l-Dopa was eff ective in treatment of Parkinson’s disease, whereas d-Dopa provided no therapeutic result, but contributed to Dopa’s toxicity.
l-Dopa is still the standard treatment for relieving symptoms of Parkinson’s disease.
Because its prolonged use can lead to complications and unpleasant side eff ects, it is often used in combination with other drugs. l-Dopa was highlighted in Oliver Sachs’s (1933–) book, Awakenings, which was made into a movie in the 1970s. Sachs’s book tells the story of how a group of individuals suff ering from encephalitis lethargica, a disease which in some cases causes its victims to exist in an unconscious sleeplike state, were “awakened.” Th e victims were individuals who had contacted the disease during an epidemic that swept the world in the 1920s. Unfortunately, l-Dopa relieved the symptoms for only a brief period.
Dopamine is used as a drug to treat several conditions. It can be injected as a solution of dopamine hydrochloride, such as in the drug Intropin. It is used as a stimulant to the heart muscle to treat heart conditions; it also constricts the blood vessels, increasing systolic blood pressure and improving blood fl ow through the body. Dopamine is used in renal medications to improve kidney function and urination. Dopamine dilates blood vessels in the kidneys, increasing the blood supply and promoting the fl ushing of wastes from the body. Dopamine is used to treat psychological disorders such as schizophrenia and paranoia.
Dopamine levels in the brain aff ect centers of reward and pleasure and is therefore associated with the action of drugs like alcohol, cocaine, heroin, and nicotine. Addiction is associated with increased dopamine levels in the reward and pleasure centers of the brain. Diff erent mechanisms aff ect how psychoactive agents aff ect dopamine in the brain. Some agents excite the dopamine-containing neurons in the brain, increasing the production and release of dopamine from vesicles. Tobacco binds to dopamine receptors and postsynaptic neurons. Over time it decreases the number of dopamine receptors, which leads to desensitization to the drug. Increase nicotine use is required to derive comparable pleasure and thus promotes addiction. Amphetamines increase release of dopamine from vesicles. Cocaine decreases the reuptake of dopamine at pre-synaptic sites, which increase the amount of dopamine available at the postpre-synaptic receptor.
Specifi c therapies to combat addiction are based on modifying dopamine brain chemistry; for example, drugs to decrease dopamine production or block dopamine receptors can be used to reduce the craving for an agent. Dopamine is the active ingredient in Zyban, a drug designed to help smokers quit.
l-Dopa was produced industrially by Hoff mann-LaRoche, using a modifi cation of the Erlenmeyer synthesis for amino acids. In the 1960s, research at Monsanto focused on increas-ing the l-Dopa form rather than producincreas-ing the racemic mixture. A team led by William S.
Knowles (1917–) was successful in producing a rhodium-diphosphine catalyst called DiPamp that resulted in a 97.5% yield of l-Dopa when used in the Hoff mann-LaRoche process.
Knowles’s work produced the fi rst industrial asymmetric synthesis of a compound. Knowles was awarded the 2001 Nobel Prize in chemistry for his work. Work in the last decade has led to green chemistry synthesis processes of l-Dopa using benzene and catechol.
Dopamine, L-Dopa | 107
34. Epinephrine (Adrenaline)
CHEMICAL NAME = 4-(1-hydroxy-2-(methylamino)ethyl) benzene-1,2-diol
CAS NUMBER = 51–43–4
MOLECULAR FORMULA = C9H13NO3 MOLAR MASS = 183.2 g/mol
COMPOSITION = C(59%) N(7.6%) H(7.2%) O(26.2%) MELTING POINT = 211°C–212°C
BOILING POINT = decomposes at 215°C DENSITY = 1.3 g/cm3 (calculated)
Epinephrine, also known as adrenaline, is a hormone continually secreted by the medulla of the adrenal gland, which is located on the top of each kidney. Epinephrine comes from the Greek epi nephros meaning “on kidneys”; adrenaline is the English equivalent of epinephrine.
Both epinephrine and adrenaline were named by original researchers without the “e” at the end and this “e” was added over time. Epinephrine is also secreted at nerve endings as a neurotrans-mitter. It was isolated by Jokichi Takamine (1854–1922) in 1900 and was the fi rst hormone to be isolated in pure form. Takamine’s success marked several years of eff orts in attempting to obtain the compound from adrenal gland secretions of animals. English researchers George Oliver (1841–1915) and Edward Albert Sharpley-Schaff er (1850–1935) had injected adrenal secretions into animals in the mid-1890s, producing a rise in blood pressure; researchers believe adrenal compounds held promise for medical applications. In 1897, John Jacob Abel (1857–1938) and Albert C. Crawford (1869–1921), working at Johns Hopkins Medical School, isolated a compound they named epinephrin, but it turned out to be the mono-benzoyl derivative of epinephrine. Takamine, who worked for the Parke, Davis & Company drug producer, visited Abel’s laboratory in 1900. Takamine’s assistant, Keizo Uenaka, success-fully crystallized pure epinephrine in 1900. Takamine applied for a patent on a “Glandular Extractive Product” on November 5, which he called adrenalin; on April 16, 1901, Takamine was granted a trademark for Adrenalin. Takamine presented and published the fi rst articles on epinephrine in 1901. Concurrently, another Parke-Davis chemist, Th omas Bell Aldrich
Epinephrine (Adrenaline) | 109
(1861–1938), also produced epinephrine and determined its correct formula. Parke, Davis began promoting Adrenalin soon after the discoveries of Takamine and Aldrich. It was pro-moted as a treatment for heart disease, goiter, deafness, and Addison’s disease.
Epinephrine is synthesized in the body from the nonessential amino acid tyrosine. Tyrosine undergoes hydroxylation to produce DOPA (3,4-dihydroxyphenylalanine). DOPA decarbox-ylation produces dopamine, which is hydroxylated to norepinephrine. Norepinephrine, which is closely related to epinephrine, performs a number of similar functions in the body. Th e pre-fi x “nor” associated with a compound is used to denote an alkylated nitrogen in the compound that has lost an alkyl group. It comes from the German N-ohne-radical, which means Nitrogen without the radical. Th erefore norepinephrine is epinephrine minus the methyl, CH3, radical on the nitrogen. Th e methylation of norepinephrine gives epinephrine. Th e synthesis is sum-marized in Figure 34.1.
Figure 34.1 Synthesis of epinephrine.
Epinephrine has several important physiological functions in the body. Its eff ect is pro-duced when it binds to receptors associated with diff erent organs. Receptors are highly specialized, and the eff ect of a hormone such as epinephrine depends on the type of recep-tor to which it binds. For this reason, epinephrine can produce diff erent eff ects in diff erent organs, so it is important to realize that physiological eff ects produced by epinephrine are not absolute. Th e physiological eff ects of epinephrine are the same whether it is produced in the adrenal gland or at the nerve endings, but because the adrenal source delivers the hormone to organs via the bloodstream, its eff ect lasts considerably longer. In general, epinephrine in the blood produces an eff ect lasting several minutes, which is several times as long as when it is produced at nerve endings.
Epinephrine is vital for normal physiological function and maintaining homeostasis, but it is secreted in large quantities during times of stress (norepinephrine is also secreted and many of its eff ects are similar to those of epinephrine). Th e stress response, sometimes called the “fi ght or fl ight” response, highlights the eff ects of epinephrine on the body. Epinephrine increases heart rate and stroke volume, resulting in an increase of blood fl ow to muscles. It produces vasoconstriction in peripheral arteries and veins, but vasodilation in other organs such as muscles, liver, and the heart. Epinephrine’s eff ect on blood vessels depends on the type of receptor it acts upon. When it acts on alpha receptors, it results in vasoconstriction;
with beta receptors it produces vasodilation. Th ere is evidence showing that vasoconstric-tion dominates at high epinephrine concentravasoconstric-tions and vasodilavasoconstric-tion at low concentravasoconstric-tions.
110 | Th e 100 Most Important Chemical Compounds
High epinephrine results in an increase in blood pressure because of vasoconstriction. High epinephrine increases lipid metabolism and the conversion of glycogen to glucose providing increased energy input to cells. During times of stress, epinephrine inhibits nonessential func-tions such as gastric secrefunc-tions and insulin production.
Epinephrine belongs to a class of hormones called catecholamines, which are derived from tyrosine and have a structure related to catechol. It is used in drugs and medications, often in the salt form as epinephrine hydrochloride. It is best known for treating allergic reactions, a condition called anaphylaxis. Anaphylaxis is caused by insect bites, foods, medications, latex, and other causes. A common device familiar to many is the epi-pen, which is an autoinjec-tor that delivers a single dose of epinephrine. EpiPen, the most popular pen, is a registered trademark of Dey Laboratories. Adult pens are designed to deliver 0.3 mg of epinephrine, and child pens deliver a 0.15 mg. dose. Injection of epinephrine almost immediately improves breathing, stimulates the heart, and reverses swelling to the face and lips. Epinephrine is also used for heart conditions, bronchitis, bronchial asthma, emphysema, and glaucoma. It is a heart stimulant. Th e use of epinephrine has recently been adopted in hair transplant surgeries to reduce bleeding.
35. Ethane
CHEMICAL NAME = ethane CAS NUMBER = 74–84–0 MOLECULAR FORMULA = C2H6 MOLAR MASS = 30.1 g/mol
COMPOSITION = C(79.9%) H(20.1%) BOILING POINT = − 88.6°C
MELTING POINT =−182.8°C
DENSITY = 1.37 g/L (vapor density = 1.05, air = 1)
Ethane is a colorless, odorless, fl ammable hydrocarbon gas that follows methane as the sec-ond simplest alkane. Th e root of ethane, “et,” is derived from the Greek word aithein, which means to burn; it was fi rst applied to the compound ether (CH3CH2OCH2CH3). Ether is a highly fl ammable compound that was fi rst prepared from the two-carbon alcohol ethanol (C2H5OH), and ethane is the two-carbon alkane. Ethane is the second most abundant com-ponent of natural gas, with sources typically containing 1–5% by volume, but some sources may contain up to 30% ethane. Ethane was fi rst synthesized in 1834 by Michael Faraday (1791–1867) through the electrolysis of acetate solutions, although Faraday believed the compound was methane. Twenty years later Adolph Wilhelm Hermann Kolbe (1818–1884) incorrectly identifi ed ethane as the methyl radical in his research, and Edward Frankland (1825–1899) prepared ethane by treating ethyl iodine (C2H5I) with metals.
Th e synthesis of ethane takes place through a process called Kolbe synthesis. In this process acetic acid (CH3COOH) undergoes electrolysis to oxidize acetate ions at the anode of an electro-chemical cell to produce acetate radicals: CH3COO- → CH3COO•. Two acetate radicals then combine to give ethane and carbon dioxide: CH3COO• + CH3COO• → C2H6 + 2CO2.
Alkanes such as ethane are relatively unreactive and reactions involving alkanes require high-energy atoms or free radicals. Th ree general types of reactions involving alkanes are combus-tion, halogenacombus-tion, and pyrolysis. Th e most common reactions of alkanes involve combustion.
Combustion of alkanes has been the primary source of heat for human civilizations throughout
112 | Th e 100 Most Important Chemical Compounds
modern history. Th e combustion of ethane is given by the equation: 2C2H6 + 7O2 → 4CO2 + 6H2O. Ethane can also be halogenated with hydrogen substituting for hydrogen. Th e reactivity of ethane decreases from fl uorine through iodine. Because fl uorine is explosively reactive, it is hard to control and iodine is generally unreactive, so most practical halogenation reactions involve chlorine and bromine. For example, ethane reacts with chlorine in an endothermic reac-tion to produce chloroethane (C2H5Cl): C2H6 + Cl2 + energy → C2H5Cl + HCl. Pyrolysis of ethane yields a host of compounds used in the petrochemical industry such as ethene (C2H4) and ethyne (C2H2). Pyrolysis is the decomposition of a compound using heat. Pyrolysis comes from the Greek root word for fi re pyr and lysis, meaning to loosen. Ethane’s primary use is as a source of ethylene. Ethylene is one of the most important compounds in the petrochemical industry owing to its high reactivity because of its double bond. Ethylene is produced from eth-ane by steam cracking. In this process etheth-ane is mixed with steam and heated to 750°C–900°C converting ethane to ethylene: C2H6 → C2H4 + H2. Th e high temperature provides the energy needed to cause the decomposition of ethane. Steam cracking of ethane produces a number of other products besides ethylene. Diff erent procedures and catalyst may be used to increase the yield of ethylene.
36. Ethene (Ethylene)
CHEMICAL NAME = ethene CAS NUMBER = 74–85–1 MOLECULAR FORMULA = C2H4 MOLAR MASS = 28.1 g/mol
COMPOSITION = C(85.6%) H(14.4%) BOILING POINT = −103.7°C
MELTING POINT = −169.4°C
DENSITY = 1.26 g/L (vapor density = 0.98, air = 1)
Ethylene is a colorless, odorless gas that is the simplest alkene hydrocarbon. It is a natural plant hormone and is produced synthetically from natural gas and petroleum. Th e double bond in ethylene makes this compound highly reactive, and the volume of ethylene used in the chemi-cal industry is greater than any other organic compound. Th e name ethylene goes back to the mid-19th century. At that time the ending “ene,” which comes from ancient Greek and means
“daughter of,” was added to names to indicate one fewer hydrogen atom that the substance from which it was derived. Th us ethylene was the daughter of ethyl, C2H5.
Ethylene is primarily obtained from the ethane and propane components of natural gas and from the naphtha, kerosene, and gas oil components of crude oil. It can also be synthesized through the dehydration of ethanol (C2H5OH). Th e production of ethylene from hydrocar-bon feedstocks involves mixing with steam and then subjecting the hydrocarhydrocar-bons to thermal or catalytic cracking. Cracking is a process in which organic molecules are broken down into smaller molecules. Th ermal cracking involves the use of heat and pressure. Catalytic crack-ing uses various catalysts to reduce the amount of heat and pressure required in the process.
Th ermal cracking of hydrocarbons to ethylene occurs between approximately 650°C and 800°C (1200°F and 1500°F). After hydrocarbons are cracked, a mixture containing ethylene and other gases such as methane, ethane, and propane is obtained. Ethylene is separated from these through physical processes such as fractional distillation, refrigeration, absorption, or adsorption.
114 | Th e 100 Most Important Chemical Compounds
Ethylene is highly reactive and is one of the most important compounds for the chemical industry. Th e highest use of ethylene is in polymerization reactions. Th e singular term polyeth-ylene implies a single repeating polymer based on the ethpolyeth-ylene monomer, but it actually refers to thousands of diff erent compounds with molar masses ranging from several hundred to several millions. Polyethylene polymers are linear, but they contain side branchings of methyl groups. Among these are several groups defi ned by their density produced under diff erent pressure regimens. High-pressure polymerization was the fi rst process developed, starting in 1935 when 8 grams of polyethylene were accidentally produced. Th e production of the fi rst polyethylene involved serendipity as researchers were investigating reactions under high pres-sure at Imperial Chemical Industries in London. In one experiment a white, waxy substance was obtained rather than the desired product. Initial attempts to duplicate the experiment failed, but then it was realized that oxygen must have been present when the fi rst polyethylene was produced. It was determined that in the initial experiment, a small leak in the reaction chamber required recharging the chamber with additional ethylene, which contained just the right quantity of air providing oxygen needed to produce polyethylene.
Th e high-pressure process, which occurs at approximately 200°C and 2,000 atmospheres, produces polyethylene with numerous areas of side branching. Regions along the molecule where side branching is abundant produces an amorphous structure, whereas straight-chain regions along the polymer are described as crystalline (Figure 36.1). Th e side branching amor-phous structure means that polymers cannot pack as closely together as polymers with less branching. Th is results in low-density polyethylene (LDPE). In addition to lower density, they also melt at lower temperature, are softer, and have less tensile strength. LDPEs have densities between 0.910 and 0.940 g/cm3 and can be identifi ed by the recycling symbol:
Figure 36.1 Crystalline HDPE is characterized by a straight-chain arrangement; LDPE has an amorphous structure.
Figure 36.1 Crystalline HDPE is characterized by a straight-chain arrangement; LDPE has an amorphous structure.