Org.Chem 3 Lec. 1 PDF

Org.Chem 3 Lec. 1 Prof.Dr. Yousif Al–Haideri Heterocyclic Compounds A heterocyclic compound is one that contains a ring made up of more than one kind of atom. In most of the cyclic compounds that we have studied so far benzene, naphthalene,cyclohexanol,cyclopentadiene the rings are made up only of c...

Org.Chem 3 Lec. 1 Prof.Dr. Yousif Al–Haideri Heterocyclic Compounds A heterocyclic compound is one that contains a ring made up of more than one kind of atom. In most of the cyclic compounds that we have studied so far benzene, naphthalene,cyclohexanol,cyclopentadiene the rings are made up only of carbon atoms; such compounds are called homocyclic or allicyclic compounds. But there are also rings containing, in addition to carbon, other kinds of atoms, most commonly nitrogen, oxygen, or sulfur. For example: Aromaticity. The Huckel 4n+2 rule Aromaticity is defined as a property of the conjugated cycloalkene which enhances the stability of a molecule due to the delocalization of electrons present in the π-π orbitals. Aromatic molecules are said to be very stable, and they do not break so easily and also reacts with other types of substances. The organic compounds which are not said to be aromatic are known as aliphatic compounds. These might be in cyclic form, but only the aromatic rings have a special kind of stability. 1|Page Org.Chem 3 Lec. 1 Prof.Dr. Yousif Al–Haideri The aromatics compounds are said to exhibit some special characteristics or called as rules which are given below- Condition #2 For Aromaticity: Every Atom In The Ring Must Be Conjugated In order for aromaticty to exist, there must also be a continuous ring of p-orbitals around the ring that build up into a larger cyclic “pi system”. In other ward that every atom around the ring must be capable of conjugation with each other. We can also say: “Every atom in the ring must have an available p orbital”, or “Every atom in the ring must be able to participate in resonance”. 2|Page Org.Chem 3 Lec. 1 Prof.Dr. Yousif Al–Haideri Remember that the “available p orbital” condition applies not just to atoms that are part of a pi bond, but also atoms bearing a lone pair, a radical, or an empty p orbital Condition 3 For Aromaticity: The Molecule Must Have [4n+2] Pi Electrons The third condition is that the cyclic, conjugated molecule must have the correct number of pi electrons. Benzene and cyclooctatetraene are both cyclic and conjugated, but benzene is aromatic and cyclooctatetraene is not. The difference is that benzene has 6 pi electrons, and cyclooctatetraene has 8. we often use is to say that benzene has [4n+2] pi electrons and cyclooctatetraene does not. 3|Page Org.Chem 3 Lec. 1 Prof.Dr. Yousif Al–Haideri “4n+2 is not a formula that you apply to see if your molecule is aromatic. It is a formula that tells you what numbers are in the magic series. If your pi electron value matches any number in this series then you have the capacity for aromaticity.” The “magic series” is: 2, 6, 10, 14, 18, 22….. (and counting up from 4 after that) We can generate this series by plugging in whole numbers (“n” = 0, 1, 2, 3, 4… ) to the [4n+2] formula. Those values of “n” have nothing to do with molecules. We are just using them to generate the series. So for n = 0 , we have [4 (0) + 2] = 2 for n = 1 , we have [4 (1) + 2 ] = 6 for n = 2, we have [4 (2) + 2 ] = 10 for n = 3, we have [4 (3) +2 ] = 14 The condition that aromatic molecules must have [4n+2] pi electrons is sometimes called “Hückel’s rule”. 4|Page Org.Chem 3 Lec. 1 Prof.Dr. Yousif Al–Haideri Note that we can count electrons in pi bonds as well as electrons from lone pairs (so long as the carbon isn’t already participating in a pi bond ) So the cyclopentadiene anion has six pi electrons – 4 from the two double bonds, and two from the lone pair on carbon. 5|Page Org.Chem 3 Lec. 1 Prof.Dr. Yousif Al–Haideri Condition #4 For Aromaticity: The Molecule Must Be Flat The fourth condition for aromaticity is that the molecule must be flat (planar). Aromaticity is such a stabilizing property (worth 20-36 kcal/mol) that generally a molecule that is ;cyclic ; conjugated; has [4n+2] pi electrons and will also be flat. 6|Page Org.Chem 3 Lec. 1 Prof.Dr. Yousif Al–Haideri Importance to Life and Industry In the biological world, heterocyclic compounds are everywhere. Carbohydrates are heterocyclic; so are chlorophyll and heme, which make leaves green and blood red and bring life to plants and animals. Heterocycles form the sites of reaction in many enzymes and coenzymes. Many heterocyclic compounds are biosynthesized by plants and animalsand are biologically active. Some heterocycles are fundamental to life, such as haem derivatives in blood and the chlorophylls essential for photosynthesis. Similarly, the paired bases found in RNA and DNA are heterocycles, as are the sugars that in combination with phosphates provide the backbones and determine the topology of these nucleic acids. The biological properties of heterocycles in general make them one of the prime interests of the pharmaceutical and biotechnology industries. A selection of just six biologically active pyridine or piperidinederivatives is shown bellow in. It includes four natural products (nicotine, pyridoxine, cocaine and morphine) and two synthetic compounds (nifedipine and paraquat). 7|Page Org.Chem 3 Lec. 1 Prof.Dr. Yousif Al–Haideri FIVE-MEMBERED RINGS Structure of pyrrole , furan , and thiophene The simplest of the five-membered heterocyclic compounds are pyrrole, furan, and thiophene, each of which contains a single hetero atom. Judging from the commonly used structures I, II, and III, we might expect each of these compounds to have the properties of a conjugated diene and of an amine, an ether, or a sulfide (thioether). Except for a certain tendency to undergo addition reactions, however, these heterocycles do not have the expected properties: thiophene does not undergo the oxidation typical of a sulfide, for example; pyrrole does not possess the basic properties typical of amines. Instead, these heterocycles and their derivatives most 8|Page Org.Chem 3 Lec. 1 Prof.Dr. Yousif Al–Haideri commonly undergo electrophilic substitution: nitration, sulfonation, halogenation, Friedel-Crafts acylation, even the Reimer-Tiemann reaction and coupling with diazonium salts. Heats of combustion indicate resonance stabilization to to the extent of 22-28kcal/mole; somewhat less than the resonance energy of benzene36 kcal/mol), but much greater than that of most conjugated dienes (about 3kcal/mole). On the basis of these properties, pyrrole, furan, and thiophene must be considered aromatic. The orbital picture of one of these molecules, pyrrole ,each atom of the ring, whether carbon or nitrogen, is held by a sigma bond to three other atoms. In forming these bonds, the atom uses three sp2 orbitals, which lie in a plane and are 120 apart ,each carbon atom of ring has left one electron and the nitrogen atom has left two electrons; these electrons occupy p orbitals. Overlap of the p orbitals gives rise to π clouds, one above and one below the plane of the ring; the π clouds coπntain a total of six electrons, the aromatic sextet as fig below Delocalisation of the π electrons stabilises the ring. As a result, pyrrole has an abnormally low heat of combustion; it tends to undergo reactions in which the stabilised ring is retained, that is, to undergo substitution. Nitrogen's extra pair of electrons, which is responsible for the usual basicity of nitrogen compounds, is involved in the π cloud, therefore, pyrrole is an extremely weak base, which causes pyrrole to be extremely reactive toward electrophilic substitution. 9|Page Org.Chem 3 Lec. 1 Prof.Dr. Yousif Al–Haideri Pyrrole is better represented by IV, Pyrrole can be considered a hybrid of structures V-IX. Donation of electrons to the ring by nitrogen is indicated by the ionic structures in which nitrogen bears a positive charge and the carbon atoms of the ring bear a negative charge.Furan and thiophene have structures that are analogous to the structure of pyrrole. Where nitrogen in pyrrole carries a hydrogen atom, the oxygen or sulfur carries an unshared pair of electrons in an sp2 orbital. Five Membered Heterocycles*The main reason for the study of pyrrole came from the work on the structure of haem; the blood respiratory pigment, and the chlorophyll; the green photosynthetic pigment of plants. *Thiophen does occur in plants in association with polyacetylenes with which they are biogenetically closely linked. *Furan occurs widely in secondary plant metabolites, especially in terpenoids. 10 | P a g e Org.Chem 3 Lec. 1 Prof.Dr. Yousif Al–Haideri *Unsubstituted pyrrole, furan, and thiophene are usually obtained from petroleum General Characteristics *Pyrrole, furan and thiophene are colourless liquids of boiling points 126o, 32o, and 84o respectively. *Pyrrole has a relatively high boiling point as compared to furan and thiophene, this is due to the presence of intermolecular hydrogen bonding in pyrrole. Structure and Aromaticity *Pyrrole furan and thiophene are aromatic because: 1) they fulfils the criteria for aromaticity, the extent of delocalisation of the nonbonding electron pair is decisive for the aromaticity, thus the grading of aromaticity is in the order of: furan< pyrrole < thiophene< benzene this order is consistent with the order of electronegativity values for oxygen (3.44), nitrogen (3.04) and thiophene (2.56). 2) They tend to react by electrophilic substitution due appearance of 11 | P a g e Org.Chem 3 Lec. 1 Prof.Dr. Yousif Al–Haideri –ve charge on carbon atoms due to delocalisation as shown in the following resonance structures Pyrrole Evidences of aromatic character in pyrrole 1) All ring bonds are intermediates between single and double bonds. 2) It tends to react by electrophilic substitution 3) Its exceptional lack of basicity and strong acidity as a secondary amine compared to the aliphatic analog (pyrrolidine). This can be explained on the basis of participation of N lone pair in aromatic sextet (see the previous resonance structures) thus the dipole moment of pyrrole compared with pyrolidine is reverted and thus protonation occurs at carbons not at N 12 | P a g e