Organic chemistry

• 1. Introduction

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  Organic chemistry rests on a single element with a stubborn habit. Carbon has a valence of four. It forms single, double, and triple bonds, and it builds structures with delocalized electrons. From that one quirk comes the majority of known chemicals, and the basis of all known life. This is the study of carbon compounds and carbon-containing materials, where chemists work out structural formulas, measure physical and chemical properties, and test how molecules react. But for centuries a different idea held the field captive. Chemists believed that compounds from living things carried a special quality, a vital force, that no laboratory could imitate. How did that belief collapse? Why does a course taught at colleges and universities carry a reputation for being very challenging? And how did a science of test tubes come to underpin pharmaceuticals, plastics, fuels, and explosives? The answers begin with soap, urine, and an accident involving a failed attempt to make quinine.

• 2. The Death Of Vital Force

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  Before the 18th century, chemists drew a hard line between two kinds of matter. Compounds taken from living organisms were thought to carry a vital force, a quality that set them apart from inorganic compounds. This was the doctrine of vitalism, also called vital force theory. Around 1816, Michel Chevreul began studying soaps made from various fats and alkalis. He separated the acids that combined with alkali to produce the soap. Because each one was an individual compound, he showed that fats from organic sources could be chemically changed into new compounds, with no vital force required. In 1828, Friedrich Wöhler went further. He produced urea, a constituent of urine, from inorganic starting materials, the salts potassium cyanate and ammonium sulfate. This Wöhler synthesis was the first time a substance thought to be organic was made in the laboratory without biological starting materials. Wöhler himself stayed cautious about claiming he had disproved vitalism. The event is now generally accepted as having done exactly that. After Wöhler came Justus von Liebig, who worked on organizing the discipline and is considered one of its principal founders.

• 3. Mauve And Magic Bullets

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  In 1856, William Henry Perkin set out to manufacture quinine and produced something else entirely. The accident gave him an organic dye now known as Perkin's mauve. Its financial success made the discovery widely known, and interest in organic chemistry climbed sharply. The era of the pharmaceutical industry began in the last decade of the 19th century, when the German company Bayer first manufactured acetylsalicylic acid, more commonly known as aspirin. By 1910, Paul Ehrlich and his laboratory group were developing the arsenic-based arsphenamine, called Salvarsan, as the first effective medicinal treatment of syphilis. With it, Ehrlich initiated the medical practice of chemotherapy. He popularized the idea of magic bullet drugs and the systematic improvement of drug therapies. His laboratory also made decisive contributions to antiserum for diphtheria and to standardizing therapeutic serums. The dye trade had its own transformation. Production of indigo from plant sources fell from 19,000 tons in 1897 to 1,000 tons by 1914, thanks to synthetic methods developed by Adolf von Baeyer. By 2002-17,000 tons of synthetic indigo were being made from petrochemicals.

• 4. A Lattice Of Carbon

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  In 1858, the idea of chemical structure arrived from two directions at once. Friedrich August Kekulé and Archibald Scott Couper, working independently, each proposed that tetravalent carbon atoms could link to one another to form a carbon lattice. The detailed patterns of bonding, they argued, could be read through skillful interpretation of chemical reactions. Kekulé later formulated the structure of benzene, the most important aromatic hydrocarbon. He first proposed the principle of delocalization, or resonance, to explain it. In an aromatic ring, every carbon atom is sp2 hybridized, which adds stability. Aromaticity in conventional cyclic compounds comes from 4n plus 2 delocalized pi electrons, where n is an integer. A ring carrying 4n conjugated pi electrons suffers particular instability, called antiaromaticity. By 1880, the number of discovered compounds had exploded, helped by new synthetic and analytical techniques. The chemist Grignard described the situation as chaos le plus complet, complete chaos, because one compound could carry multiple names. That disorder led to the Geneva rules of 1892, and naming would eventually fall under specifications from IUPAC, the International Union of Pure and Applied Chemistry.

• 5. Reading A Molecule

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  Nuclear magnetic resonance spectroscopy is the most commonly used technique for working out what an organic compound actually is. It can often assign the complete connectivity of atoms, and even stereochemistry, using correlation spectroscopy. This works because the two principal atoms of organic chemistry, hydrogen and carbon, occur naturally with NMR-responsive isotopes, 1H and 13C. Mass spectrometry gives the molecular weight of a compound and, from its fragmentation patterns, clues to its structure. High-resolution mass spectrometry can usually identify the exact formula and is used in place of elemental analysis, which destroys the sample to determine its elemental composition. Crystallography becomes useful when a single crystal is available, and modern hardware and software can determine a structure within hours. Because organic compounds often exist as mixtures, chemists rely on chromatography to assess purity, including HPLC and gas chromatography. Older separation methods include distillation, crystallization, evaporation, magnetic separation, and solvent extraction. The chemical tests once called wet methods have largely given way to spectroscopic and computer-intensive analysis. Even so, infrared spectroscopy, optical rotation, UV/VIS spectroscopy, refractive index, and density still serve specific identification tasks.

• 6. Behavior And Building Blocks

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  Para-dichlorobenzene, the odiferous constituent of modern mothballs, is a well-known organic compound that sublimes rather than simply melting. Many organic compounds melt and boil, while inorganic materials often melt but degrade instead of boiling. Melting and boiling points correlate with a molecule's polarity and molecular weight, and above 300 degrees Celsius most organic compounds lose stability, with some exceptions. Neutral organic compounds tend to be hydrophobic, dissolving more readily in organic solvents than in water. The exceptions include compounds with ionizable groups, plus low molecular weight alcohols, amines, and carboxylic acids, where hydrogen bonding occurs. Functional groups sit at the center of how chemists classify and predict. A functional group is a molecular module whose reactivity stays roughly the same across different molecules. Alcohols, for instance, all carry the C-O-H subunit, tend to be somewhat hydrophilic, usually form esters, and convert to the corresponding halides. Acidity and basicity follow measurable pKa values. Acyl chlorides have the lowest pKa and are most likely to be attacked, followed by carboxylic acids at 4, thiols and malonates at 13, alcohols at 17, aldehydes at 20, nitriles and esters at 25, and amines at 35. Amines are very basic and act as excellent nucleophiles.

• 7. Chains, Rings, And Cages

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  Cyclopropane, written (CH2)3, is the smallest member of the cycloalkane family, a three-membered ring. The most stable rings hold five or six carbon atoms, though large macrocycles and smaller rings are common. Aliphatic hydrocarbons divide by saturation into three homologous series. Alkanes, also called paraffins, have only single bonds. Alkenes, the olefins, carry one or more double bonds. Alkynes, the acetylenes, carry one or more triple bonds. When a heteroatom, generally oxygen, sulfur, or nitrogen, sits inside a ring, that ring becomes a heterocycle. Pyridine and furan are aromatic heterocycles, while piperidine and tetrahydrofuran are their alicyclic counterparts. Heterocycles fill aniline dyes and medicines, and they run through alkaloids, vitamins, steroids, and nucleic acids such as DNA and RNA. Carbon's talent for forming chains and networks linked by carbon-carbon bonds is what makes polymers possible, built from repeating monomers. The most dramatic carbon cages came in 1985, when Sir Harold W. Kroto of the United Kingdom, with Richard E. Smalley and Robert F. Curl Jr. of the United States, vaporized graphite rods with a laser in helium gas. They obtained molecules of 60 carbon atoms, a hollow sphere of 12 pentagonal and 20 hexagonal faces resembling a soccer ball. They named it buckminsterfullerene, after the architect R. Buckminster Fuller, and the trio won the Nobel Prize in 1996.

• 8. Designing The Molecule

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  Lysergic acid and vitamin B12 mark how far the multiple-step assembly of complex molecules, called total synthesis, has climbed since the start of the 20th century. Earlier targets ran from glucose to terpineol, and cholesterol-related compounds opened routes to complex human hormones and their modified derivatives. Organic synthesis works like an applied science bordering engineering, treating each novel compound as a problem to solve. A chemist chooses optimal reactions from optimal starting materials, and a complex compound can demand tens of sequential steps. One strategy, retrosynthesis, was popularized by E.J. Corey. It begins with the target molecule and splits it into pieces according to known reactions, then treats each precursor the same way until cheap, available starting materials are reached. The route is then written in reverse to give the actual synthesis. Because every compound has multiple possible syntheses, chemists can construct a synthetic tree of options. The discipline still leans on luck meeting preparation, the same combination that handed Perkin his mauve and Wöhler his urea, only now aimed at molecules of deliberate, towering complexity.