Al Farabi Kazakh National University

Al Farabi Kazakh National University

Faculty of chemistry and chemical technology

SIW: 6 and more membered heterocycles

Done by: Kaydar Bayan

Almaty, 2014

Cyclic compounds

Ø Six-membered rings with one heteroatom

The nomenclature used for the various monocyclic nitrogen-containing six-membered ring compounds is given below. Positions on the ring are shown for pyridine, Arabic numerals being preferred to Greek letters, although both systems are used. The pyridones are aromatic compounds because of contributions to the resonance hybrid from charged resonance forms such as that shown for 4-pyridone.

Mono-, di-, and trimethylpyridines—that is, pyridines with one, two, or three attached methyl groups, respectively—are called picolines, lutidines, and collidines, respectively, with the position of the methyl groups denoted by numbers—e.g., 2,4,6-collidine. Pyridine-2-, -3-, and -4-carboxylic acids also have widely used trivial names: picolinic, nicotinic (derived from nicotine, of which it is an oxidation product), and isonicotinic acid, respectively. Pyridine itself and the picolines, lutidines, and collidines occur in coal tar and bone oil. Pyridine derivatives are also of great biological importance. For example, nicotinic acid is more commonly known as the B-complex vitamin niacin; a nutritionally equivalent form of niacin is nicotinamide, or niacinamide. Pyridoxine is another member of the B complex, vitamin B6. The structures of pyridoxine and nicotinamide are:

Two coenzymes involved in many important metabolic reactions in living cells, nicotinamide adenine dinucleotide (NAD, also called coenzyme I) and nicotine adenine dinucleotide phosphate (NADP, coenzyme II), are derived from nicotinamide, and the coenzyme pyridoxal phosphate (codecarboxylase) is a physiologically active form of pyridoxine. Many alkaloids contain a pyridine or piperidine ring structure, among them nicotine (mentioned in the previous section for its pyrrole ring) and piperine (one of the sharp-tasting constituents of white and black pepper, from the plant species Piper nigrum), with the structures shown.

Pyridine, which once was extracted commercially from coal tar but now is prepared catalytically from tetrahydrofurfuryl alcohol and ammonia, is an important solvent and intermediate used to make other compounds. Vinylpyridines such as

are important monomer building blocks for plastics, and fully saturated pyridine, piperidine, is used in rubber processing and as a chemical raw material.

Pharmaceutically important pyridines include the tuberculostat isoniazid (isonicotinic acid hydrazide), the anti-AIDS-virus drug nevirapine, the vasodilator nicorandil, used for treating angina, the urinary-tract analgesic phenazopyridine, and the anti-inflammatory sulfa drug. 1-(1-phenylcyclohexyl) piperidine (PCP, phencyclidine) was originally used as an anesthetic, but its powerful hallucinogenic properties have led to abuse. Diquat, paraquat, clopyralid, and diflufenican are well-known pyridine derivatives used as herbicides.

Shown in the structural formulas below are two isomeric benzopyridines (upper pair) and two isomeric dibenzopyridines (lower pair), with their common names and accepted numberings. All four compounds and some of their alkyl derivatives have been obtained from coal tar. Each of them is also the parent substance of a class of alkaloids. Of these, the quinolines (e.g., quinine and other derivatives, still obtained from the Cinchona tree) and the isoquinoline (e.g., morphine) groups are particularly well-known.

Quinoline itself can be used to manufacture nicotinic acid and other compounds such as drugs and dyes. The production of synthetic quinoline far exceeds that from coal tar. Morphine, codeine, and thebaine—all containing partially reduced isoquinoline rings—are alkaloids of the opium poppy and have been used for many centuries as hypnotics and analgesics. The semisynthetic derivative of morphine, heroin, is an even more powerful hypnotic and a highly addictive drug.

Important synthetic derivatives of the benzo- and dibenzopyridines include cyanine dyes, used as sensitizers in silver halide photographic emulsions, and quinophthalone dyes, applied in plastics, polymer textiles, paper, cosmetics, transfer-printing processes, electronic photography, and laser dyes. Other derivatives are useful bacteria-staining agents for microscopy, antiseptics such as the coal-tar dye acriflavine, antimalarial agents such as mepacrine (quinacrine) and chloroquine, antibacterial agents such as ciprofloxacin, trypanocides (drugs that destroy trypanosomes, which are parasitic protozoans responsible for Chagas disease, sleeping sickness, and other serious infectious illnesses) such as ethidium bromide, and the reagent oxine (8-hydroxyquinoline or 8-quinolinol), used in analytical chemistry.

Positively charged ions (cations) of pyrylium and thiopyrylium are the parent six-membered, aromatic, monocyclic oxygen and sulfur compounds of their respective groups.

An uncharged aromatic (completely conjugated) six-membered ring containing an oxygen or sulfur atom is possible only if the ring contains a carbonyl group (i.e., a ring carbon atom linked by a double bond to an oxygen atom not in the ring), as in the pyrones.

The pyrans contain extra hydrogen atoms, the position of which is indicated in structural diagrams by a number followed by an H. Certain sugars—a typical example is the monosaccharide glucose—are called pyranoses because they contain six-membered tetrahydropyran rings, with the structure:

Pyrone derivatives are present in natural products. Kojic acid, for example, is an antibiotic derived by action of certain molds on starches or sugars. The steroid bufotalin and its poisonous ester bufotoxin are obtained from the skin glands of toads (genus Bufo; see steroid: Structural relationships of the principal categories of steroids).

The benzopyrylium cation is the parent of a large number of natural products. Chroman, or 3,4-dihydro-2H-1-benzopyran, is itself not found in nature, but the chroman unit is present in many natural products. Vitamin E (α-tocopherol), a substituted chroman, is found in plant oils and the leaves of green vegetables, whereas coumarin, or 2H-1-benzopyran-2-one, used in perfumes and flavourings, and its derivative dicoumarin (dicumarol, or discoumarol), a blood anticoagulant, are products of living organisms.

Ø Rings with seven or more members

As the size of the ring increases, the range of compounds that can be obtained by varying the number, type, and location of the heteroatoms increases enormously. Nevertheless, the chemistry of heterocyclic compounds with rings seven-membered or larger is much less developed than that of five- and six-membered ring heterocycles, although these compounds are usually stable and some of them have found practical application. Of the seven-membered ring compounds, one-heteroatom heterocycles—azepines, oxepines, and thiepines—and their derivatives are the most comprehensively studied. The increase in ring size constrains these compounds to be nonplanar in order to lessen the ring strain. Nonplanarity, however, affects aromaticity, so these heterocycles react as cyclic polyenes (compounds with noninteracting, alternating single and double bonds). Azepine and oxepine rings are important constituents of numerous naturally occurring alkaloids and metabolic products of marine organisms. The azepine derivative caprolactam is produced commercially in bulk for use as an intermediate in the manufacture of nylon-6 and in production of films, coatings, and synthetic leather. Seven-membered heterocycles with one or two nitrogen atoms in the ring are structural units of widely used psychopharmaceuticals such as imipramine (trade name Prazepine)—the first of the tricyclic antidepressants—and the tranquilizer diazepam (trade name Valium).

Of the larger ring heterocycles, the most important are the crown ethers, which contain one or more heterocyclic rings comprising 12 or more ring atoms and involving a number of various heteroatoms, usually nitrogen, oxygen, or sulfur. The heteroatoms are usually separated by two-carbon or three-carbon units (ethylene or propylene units, respectively). The first crown ether, dibenzo-18-crown-6, was synthesized in 1960. The first number in a crown ether name indicates the total number of atoms involved in the macrocycle (i.e., the large ring), while the second indicates the number of heteroatoms in that ring. The remarkable feature of crown ethers, which stimulated the explosive development of their chemistry, is their ability to selectively bind the ions of metal elements (e.g., potassium and sodium) and whole organic molecules inside their cavities, the selectivity for a particular ion or molecule being directly related to the size of the macrocycle. Because of this feature, crown ethers have found wide application as ion transporters, as materials for ion-selective electrodes used in environmental testing for various metal ions, as sensitizers in photography, in medical diagnostics, and for the separation of radioactive isotopes.

Although crown ethers are not found in nature, some larger ring heterocycles that possess similar pronounced binding abilities exist as natural products. An example is the porphyrins, which are widely distributed as biological pigments—e.g., the magnesium-binding chlorophylls and the iron-binding heme groups of hemoglobin and myoglobin (see above Five-membered rings with one heteroatom; see also chelate).

Rings with uncommon heteroatoms

In addition to the nitrogen, oxygen, and sulfur atoms commonly found in heterocycles, a large number of other elements form such rings—of greater or lesser stability. Such compounds are as yet of little practical importance. Some of the main classes are described below according to the elements they contain.

HALOGENS, SELENIUM, AND TELLURIUM

Cyclic chloronium, bromonium, and iodonium ions—ions of the halogen elements chlorine, bromine, and iodine, respectively—have been prepared. Of these, only the iodine derivative has much stability.

Many heterocycles containing selenium (Se) atoms are known. Selenium shows much similarity in behaviour to sulfur; hence, selenophene, with the structure shown, resembles thiophene quite closely.

PHOSPHORUS, ARSENIC, ANTIMONY, AND BISMUTH

Phosphorus (P), arsenic (As), antimony (Sb), and bismuth (Bi), which are all members of group Va of the periodic table of elements (see nitrogen group element), form a closely related group of heterocycles. There is, however, little similarity between their properties and those of the corresponding derivatives of nitrogen, a member of the same group. Although phosphorus-containing heterocycles have long been known, the heterocyclic chemistry of arsenic, antimony, and bismuth has made significant progress only in recent years because of the decreased stability of heterocycles involving a heavy element. Parent five-membered heterocycles with arsenic, antimony, or bismuth have yet to be isolated, and six-membered bismuth heterocycles are unknown. Because of this instability, those antimony and bismuth compounds that have been synthesized have found little practical application.

References:

1. www.wikipedia.org

2. www.xumuk.ru

3. http://sparkcharts.sparknotes.com

4. http://www.britannica.com/EBchecked/topic/147930/cyclic-compound

5. http://www.britannica.com/EBchecked/topic/264227/heterocyclic-compound/277877/Six-membered-rings-with-one-heteroatom

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