chapter 18 Heterocyclic compounds杂环化合物

The reaction takes place at C-2 and C-4
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If the leaving groups at C-2 and C-4 are different, the incoming nuclophile will preferentially substitute for the weak base(the better leaving group). For example
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Why reactions take place at C-3?
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Pyridine is more reactivity toward nucleophilic aromatic substitution than benzene. Mechanism for nucleophilic aromatic substitution
Thiophene, with the least electronegative heteroatom, has the greatest resonance energy While furan has the smallest resonance energy. Relative resonance energies of some aromatic compounds
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Unsaturated five-membered-ring heterocycles
Pyrrole, furan, and thiophene are five-memberedring heterocycles.Pyrrole, furan, and thiophene are aromatic because they are cyclic and planar, every carbon in the ring has a p orbital, and the π cloud contains three pairs of π electrons.
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Indole, benzofuran, and benzothiophene Electrophilic substitution: indole undergoes electrophilic substitution primarily at C-3, benzofuran primarily at C-2, and Benzothiophene about equally well at C-2 and C-3. For example,
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Unsaturated six-membered-ring heterocycles Pyridine When one of the carbons of a benzene ring is replaced by a nitrogen,the resulting compound is called pyridine.
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Ring- open reaction Usually, pyrrole does not undergo this reaction, but it is unstable in strong acidic solutions because of polymerization. Furan is easily hydrolyzed in acidic aqueous solution. Thiophene can be reduced to alkane under Ni Catalyst by H2.
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The relative reactivities of them are reflected in the Lewis acid required to catalyze a Friedel-Crafts Acylation reaction.
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The oxygen of furan is more electronegative than the nitrogen of pyrrole, so the oxgen is not as effective as nitrogen in donating electrons into the ring.
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Dipole moment of five-member-ring heterocycles
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Electrophilic aromatic substitution
more reactive than benzene,Substitution occurs preferentially at C-2, if both positions adjacent to the heteroatom are occupied, substitution will take place at C-3.
pounds
eterocycles include valium, a synthetic tranquilizer, and serotonin, a neurotransmitter.
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Saturated heterocycles
Chapter 18 Heterocyclic compounds
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Heterocyclic compounds ,or heterocycles, are cyclic compounds in which one or more of the atom of the ring are heteroatoms. A variety of atoms can be incorporated into ring structures. In this chapter, we will only consider the hetroatoms N, O,S. Almost all the compounds we know as drugs, most vitamins, and many other natural products are heterocycles.
Thiophene is less reactive than furan, because sulfur’s p electrons are in 3p orbital, which overlaps less effectively than the 2p orbital of Nitrogen or oxygen with the 2p orbital of carbon.
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natural product is a compound synthesized by a plant or an animal. Alkaloids are natural products containing one or more nitrogen heteroatoms that are found in the leaves, bark, roots, or seeds of the plants.
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Substituted pyridines undergo many of the side-chain reactions that substituted benzenes undergo. When 2-or 4-aminopyridine is diazotized,α-pyridone or γ-pyridone is formed
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Quinolline and isoquinoline
Quinoline and isoquinoline are known as benzopyridines,because they have both benzene and pyridine rings. They Are aromatic compounds
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Because it is aromatic, pyridine undergoes electrophilic substitution. Pyridine’s electron-withdrawing nitrogen causes the ring carbons to have significantly less electron density than the ring carbons of benzene. Relative reactivity toward electrophilic substitution
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These electrons are part of the π cloud
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These electrons are in a sp2 orbital
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Pyrrole is an extremely weak base .
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The electron-withdrawing nitrogen causes the αHydrogens of alkyl groups attached to the 2- and 4positions of the pyridine ring to have about the same acidity as the α-hydrogens of ketones.