8-methyl-N-vanillyl-6-nonenamide (Capsaicin) Chapter 17: Benzene and Aromaticity Buckminsterfullerene TNT
Key points & objectives: • Aromatic molecules are cyclic, conjugated, flat, and unusually stable • 4n + 2 electrons (n = 0, 1, 2, …. • Hydrocarbon aromatics: benzene, naphthalene, anthracene, toluene, xylylene • Heterocyclics: pyridine, pyrimidine, imidazole, pyrrole, thiophene, furan, indole…. • Molecular orbitals using Frost diagrams (inscribed circles) • Ring current deshields NMR signals – downfield
Benzene 1st isolated by Michael Faraday in 1825 From “Benzoin,” corrupt form of the Arabic "lubanjawi” for the “frankincense of Java”
Frankincense Not “aromatic” in the technical sense triterpene Cancer drug anti-inflammatory hepatotoxicity Boswellia sacra
Aromatic-fragrant myrth Commiphoramyrrha tree Antiseptic, embalming agent, incense
Cinnamon (2E)-3-phenylprop-2-enal cinnamaldehyde Diabetes Antimicrobial antioxidant
Capsaicin 8-methyl-N-vanillyl-6-nonenamide (Capsaicin) 16,000,000 Scovilles psoriasis relieve the pain of peripheral neuropathy trigger apoptosis in human colon and lung cancer
Vanilla Tincture (ethanol extract) of vanilla aphrodisiac and a remedy for fevers catecholamines (including adrenaline) addictive
Aromatic molecules • Flat • Conjugated • (4n +2) pi electrons • Unusually stable • Ring current (deshielding protons)
Anesthetics & analgesics Advil, and Motrin
Sunscreens Only complete UVA block
Skin Damage • Very high energy radiation (UVC) is currently blocked by the ozone layer (ozone hole issue) • High energy radiation (UVB) does the most immediate damage (sunburns) • But lower energy radiation (UVA) can penetrate deeper into the skin, leading to long term damage Source: N.A. Shaath. The Chemistry of Sunscreens. In: Lowe NJ, Shaath NA, Pathak MA, editors. Sunscreens, development, evaluation, and regulatory aspects. New York: Marcel Dekker; 1997. p. 263-283.
Sources and Names of Aromatic Hydrocarbons • From high temperature distillation of coal tar • Heating petroleum at high temperature and pressure over a catalyst
Polychlorinatedbiphenyls PCB’s Thermally stable, electrically insulating heat transfer liquid Casting wax for lost wax process for making metal things
dichlorodiphenyltrichloroethane Malaria mosquito Mueller 1948 Nobel Prize in Medicine
Monosubstituted Benzenes • Most monosubstituted aromatics are named using -benzene as the parent name preceded by the substituent name (as a prefix; all one word): nitro ethyl fluoro fluorobenzene nitrobenzene ethylbenzene
Alkyl-substituted Benzenes • Alkyl substituted benzenes are named according to the length of the carbon chain of the alkyl group. • With six carbons or fewer in the alkyl chain, they are named as ‘alkylbenzene.’ • e.g., propylbenzene:
Alkyl-substituted Benzenes • With more than six carbons in the alkyl chain, they are named as a ‘phenylalkane,’ where the benzene ring is named as a substituent (phenyl) on the alkane chain • e.g., 4-phenylnonane 4-phenylnonane
The Benzyl Group • The benzyl group is a common name for a methyl substituted benzene (toluene) having substitution for one of the hydrogens on the methyl group. the benzyl group benzyl bromide benzyl alcohol
Common Names of Subs. Benzenes • There are a number of nonsystematic (common) names commonly used for certain monosubstituted benzenes (see next slide) • These ten common names should be memorized. • These common names are used as base names when naming more their more highly substituted derivatives. Examples of these will be given later.
Disubstituted Benzenes • Disubstituted benzenes can be named in one of two ways. Each method describes the relative positions of the two groups on the benzene ring. • Systematic numbering of the aromatic ring. • Using the prefixesortho-, meta-, or para-. • When numbering the ring carbons, carbon # 1 is always a substituted carbon. • The substituents are listed alphabetically.
Disubstituted Benzenes ortho- (abbreviated o- ) = 1,2-disubstituted (two groups on adjacent carbons on the ring)
Disubstituted Benzenes meta- (abbreviated m- ) = 1,3-disubstituted (two groups having one unsubstituted carbon between them)
Disubstituted Benzenes para- (abbreviated p- ) = 1,4-disubstituted (two groups on opposite sides of the ring)
Disubstituted Benzenes • When one of the substituents changes the base name, either o-, m-, and p- or numbers may be used to indicate the position of the other substituent. • Carbon # 1 is always the carbon bearing the substituent that changes the base name. 4 1 2 3 2 1 p-bromoaniline or 4-bromoaniline o-chlorophenol or 2-chlorophenol
Common Names of Disubs. Benzenes • There are a few nonsystematic (common) names for disubstituted benzenes that you should be familiar with:
Disubstituted Benzenes • Relative positions on a benzene ring • ortho- (o) on adjacent carbons (1,2) • meta- (m) separated by one carbon (1,3) • para- (p) separated by two carbons (1,4) • Describes reaction patterns (“occurs at the para position”)
Polysubstituted Benzenes • Polysubstituted benzenes must be named by numbering the position of each substituent on the ring (with more than two substituents, o-, m-, and p-can NOT be used.) • The numbering is carried out to give the substituents the lowest possible numbers. Carbon #1 always has a substituent. • List the substituentsalphabetically with their appropriate #s. 2 1 3 4 2-ethyl-1-fluoro-4-nitrobenzene
Polysubstituted Aromatics having a Common base name • Common names of the monosubstituted benzenes are used as parent names for polysubstituted aromatics when one of the substituents changes the base name. • For such rings with common names, the carbon bearing the substituent responsible for the common name is always carbon #1. • The substitutents are listed in alphabetical order. toluene 1 chloro 2 bromo 3 5 4 5-bromo-2-chlorotoluene
Polysubstituted Benzenes 4 1 3 2 3 2 5 1 4 4-bromo-2-ethyl-1-nitrobenzene 5-bromo-2-chlorophenol
Polysubstituted Benzenes 2 1 1 2 3 6 3 6 4 5 5 4 2-bromo-6-chloro-4-nitrotoluene 1-bromo-3-chloro-2-ethyl-5-nitrobenzene
Naming Benzene as a Substituent • A benzene substituent is called a phenyl group, and it can be abbreviated in a structure as “Ph-”. • Therefore, benzene can be represented as PhH, and phenol would be PhOH.
Polycyclic Aromatic Hydrocarbons (PAH) Metabolic byproducts of benzo [a] pyrene react with DNA to form adducts, leading to carcinogenesis (cancer).
Naphthalene Orbitals • Three resonance forms and delocalized electrons
13C NMR Absorptions of Dibromobenzenes Figure 17.2 • The number of signals (lines) in the 13C NMR spectrum of a disubstituted benzene with two identical groups indicates whether they are ortho, meta, or para to each other.
Drugs that Contain a Benzene Ring Figure 17.5
Pyridine • A six-membered heterocycle with a nitrogen atom in its ring • electron structure resembles benzene (6 electrons) • The nitrogen lone pair electrons are not part of the aromatic system (perpendicular orbital) • Pyridine is a relatively weak base compared to normal amines but protonation does not affect aromaticity
Pyrrole • A five-membered heterocycle with one nitrogen • electron system similar to that of cyclopentadienyl anion • Four sp2-hybridized carbons with 4 p orbitals perpendicular to the ring and 4 p electrons • Nitrogen atom is sp2-hybridized, and lone pair of electrons occupies a p orbital (6 electrons) • Since lone pair electrons are in the aromatic ring, protonation destroys aromaticity, making pyrrole a very weak base
Structure and Stability of Benzene: Molecular Orbital Theory • Benzene reacts slowly with Br2 to give bromobenzene (where Br replaces H) • This is substitution rather than the rapid addition reaction common to compounds with C=C, suggesting that in benzene there is a higher barrier
Heats of Hydrogenation as Indicators of Stability • The addition of H2 to C=C normally gives off about 118 kJ/mol – 3 double bonds would give off 356kJ/mol • Two conjugated double bonds in cyclohexadiene add 2 H2 to give off 230 kJ/mol • Benzene has 3 unsaturation sites but gives off only 206 kJ/mol on reacting with 3 H2 molecules • Therefore it has about 150 kJ more “stability” than an isolated set of three double bonds