Save my name, email, and website in this browser for the next time I comment. Remember Me. Heterocyclic Chemistry by John A.
By Yogesh Maurya December 6, 6 Comments. Joule School of Chemistry, The University of Manchester, UK Keith Mills Chemistry Consultant, Ware, UK Heterocyclic compounds have a wide range of applications but are of particular interest in medicinal chemistry, and this has catalysed the discovery and development of much heterocyclic chemistry and methods.
Brief Contents [Chapter vise] 1. Heterocyclic Nomenclature 2. Structures and Spectroscopic Properties of Aromatic Heterocycles 3. Substitutions of Aromatic Heterocycles 4. Organometallic Heterocyclic Chemistry 5. Methods in Heterocyclic Chemistry 6.
Ring Synthesis of Aromatic Heterocycles 7. Typical Reactivity of Pyridines, Quinolines and Isoquinolines 8. Pyridines: Reactions and Synthesis 9. Quinolines and Isoquinolines: Reactions and Synthesis Pyryliums, 2- and 4-Pyrones: Reactions and Synthesis Benzopyryliums and Benzopyrones: Reactions and Synthesis Typical Reactivity of Pyrroles, Furans and Thiophenes Pyrroles: Reactions and Synthesis Thiophenes: Reactions and Synthesis Furans: Reactions and Synthesis Indoles: Reactions and Synthesis Benzo[b]thiophenes and Benzo[b]furans: Reactions and Synthesis Isoindoles, Benzo[c]thiophenes and Isobenzofurans: Reactions and Synthesis Typical Reactivity of 1,3- and 1,2-Azoles and Benzo-1,3- and -1,2-Azoles Benzanellated Azoles: Reactions and Synthesis The cyclic systems containing only carbon atoms are called carbocyclic and the cyclic systems containing carbons and at least one other element are called heterocyclic.
Though a number of heteroatoms are known to be part of the heterocyclic rings, the most common heteroatoms are nitrogen, oxygen or sulphur.
A heterocyclic ring may contain one or more heteroatoms which may or may not be same. Also the rings may be saturated or unsaturated. Nearly half of the known organic compounds contain at least one heterocyclic ring.
Many heterocyclic compounds occur naturally and are actively involved in biology e. The study of heterocyclic chemistry is a vast and expanding area of chemistry because of their applications in medicine, agriculture, photodiodes and other fields. Heterocyclic compounds may be classified as aliphatic and aromatic heterocycles.
The aliphatic heterocycles are the cyclic analogues of amines, ethers and thioethers and their properties are influenced by the ring strain. The three and four membered aliphatic heterocyclic rings are more strained and reactive compared to five and six membered rings. The aromatic nature of five and six-membered heterocycles is discussed in Sec. The p-orbitals on each carbon atom perpendicular to the plane of the ring then interact with each other.
Energy Fig. However, if the number of electron pairs is even total number of electrons is 4n , the last pair will occupy the degenerate orbital pair so that one electron is present in each degenerate orbital with parallel spins Fig. Therefore cyclic conjugated polyenes are aromatic if they are thermodynamically more stable than the corresponding open-chain analogs and it is antiaromatic if it is less stable.
Molecules which show neither stabilization nor destabilization are known as non-aromatic. Planar unsaturated heterocycles containing five atoms can be considered aromatic system if they have an uninterrupted cycle of p- orbitals containing six electrons in all. Pyrrole, furan and thiophene are examples of this type. In all these heterocycles, four carbon atoms and the heteroatom are sp2 hybridized.
The third p-orbital, which is orthogonal to the plane of the atoms, contributes its lone pair of electrons. The resonance structures of pyrrole show that nitrogen donates electrons to the ring Fig. It is evident from the resonance structures given above and the data in Fig. However, unlike pyrrole, the delocalization is not as extensive in furan because of high electronegativity of oxygen and so the lone pairs are held more tightly by the oxygen.
Thiophene with the least electronegative heteroatom is regarded as aromatic and has the highest resonance energy whereas furan has the least resonance energy. All these heterocycles have lower resonance energies than benzene. These are more reactive than benzene towards electrophilic substitution because of the increased electron density on each carbon in the ring. Therefore, the attack of the electrophile which is the rate determining step is more facile with these heterocycles.
Unlike pyrrole, furan and thiophene do not undergo protonation. Therefore, if pyrrole is protonated, it loses its aromaticity as the non bonding electrons are no more available for delocalization to form the aromatic sextet. The number of five membered aromatic heterocycles is much larger than that of the six membered aromatic heterocycles.
This is because one of the heteroatoms in the ring can be divalent and so more heteroatoms can be incorporated into the five-membered rings than six-membered rings. High boiling point of pyrrole is due to hydrogen bonding between pyrrole molecules. Pyridine All six membered fully unsaturated heterocycles are related to benzene as these can be represented by replacement of one or more CH groups by a trivalent heteroatom. Pyridine ring consists of five carbon atoms and a nitrogen atom.
Pyridine is a planar molecule. The ring is a slightly distorted hexagon as the C—N bonds are shorter than C—C bonds. N N Fig. The lone pair of electrons on sp2 hybridized nitrogen is responsible for the basicity of pyridine and it behaves like a tertiary amine. Its aromaticity is not affected by protonation unlike pyrrole which loses aromaticity upon protonation. The lone pair of nitrogen in pyridine is sp2 hybridized which is more electronegative than the sp3 hybridized nitrogen.
Therefore pyridine is less basic than amines and anilines. Heterocycles in which other benzenoid CH groups are replaced with nitrogen, also behave similarly. Because of the involvement of lone pair of nitrogen, charge separated cannonical forms can be written for indole as shown in Fig. Quinoline is high boiling liquid b. Quinoline and isoquinoline are weak bases but slightly more basic than pyridine but less basic than anilines since the nitrogen in quinoline and isoquinoline is more electronegative being sp2 hybridized compared to sp3 hybridized nitrogen of anilines.
Isoquinoline has higher dipole moment 2. Methods of Preparation Synthesis of Furan, Pyrrole and Thiophene i Furfural can be prepared by dehydration and cyclization of pentoses. Furfural undergoes decarbonylation to give furan eq.
NH3, steam Two moles of ethyl acetoacetate are used eq. Picolines can be oxidised to corresponding pyridine carboxylic acids and converted to other pyridine derivatives. There are several modification of the Hantzsch synthesis. Aromatic amines do not give good yields. The Fischer-indole synthesis is carried out by heating phenyl hydrazone or substituted phenyl hydrazone of an aldehyde or ketone.
The reaction is catalyzed by zinc chloride, polyphosphoric acid, sulphuric acid or boron trifluoride and proceeds with elimination of a molecule of ammonia eqs. Me Me ZnCl The most acceptable mechanism is given in Scheme 1. The acid acts as a dehydrating agent and an Glycerol, conc.
The reaction proceeds in the following manner Scheme 2. The cyclized intermediate undergoes subsequent dehydration and oxidation to give quinoline. Oxidation has been reported with other oxidising agents as well. Quinolines with substituent in the benzene ring may be obtained by starting from substituted anilines.
R conc. Dehydrogenation of 3,4-dihydroquinoline over Pd, S or Se yields 1- substituted isoquinoline Scheme 3. The two modifications are Pictat-Gams synthesis eq. It has already been described in Sec. The electrophilic substitution takes place preferentially at 2-position C
0コメント