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1、Heterocyclic CompoundsAssoc. prof. Lubomir Makedonski, PhDMedical University of VarnaOther elements such as nitrogen and oxygen can be included in the rings. When they are, the compounds are called heterocyclic compounds. The hetero- part of the name means that more than one kind of element is inclu
2、ded within the ring and -cyclic, of course, indicates that there is at least one ring present in the compound.Compounds classified as heterocyclic probably constitute the largest and most varied family of organic compounds. After all, every carbocyclic compound, regardless of structure and functiona
3、lity, may in principle be converted into a collection of heterocyclic analogs by replacing one or more of the ring carbon atoms with a different element. Even if we restrict our consideration to oxygen, nitrogen and sulfur (the most common heterocyclic elements), the permutations and combinations of
4、 such a replacement are numerous. Some important heterocyclic compounds with N-heteroatom Pyrrol Indole Pyridine Pyrazole Imidazole Pyramidine PurineNomenclatureDevising a systematic nomenclature system for heterocyclic compounds presented a formidable challenge, which has not been uniformly conclud
5、ed. Many heterocycles, especially amines, were identified early on, and received trivial names which are still preferred. An easy to remember, but limited, nomenclature system makes use of an elemental prefix for the heteroatom followed by the appropriate carbocyclic name. A short list of some commo
6、n prefixes is given in the following table.Examples of this nomenclature are: ethylene oxide = oxacyclopropane furan = oxacyclopenta-2,4-diene pyridine = azabenzene morpholine = 1-oxa-4-azacyclohexane. Elementoxygen sulfur selenium nitrogen phosphorous silicon boron ValenceIIIIIIIIIIIIIVIIIPrefixOxa
7、ThiaSelenaAzaPhosphaSilaBoraAll the previous examples have been monocyclic compounds. Polycyclic compounds incorporating one or more heterocyclic rings are well known. A few of these are shown in the following diagram. Thus, the location of a fused ring may be indicated by a lowercase letter which d
8、esignates the edge of the heterocyclic ring involved in the fusion, as shown by the pyridine ring in the green shaded box.Heterocyclic rings are found in many naturally occuring compounds. Most notably, they compose the core structures of mono and polysaccharides, and the four DNA bases that establi
9、sh the genetic codeHeterocyclic compounds are: Heterocyclic compounds with three - membered rings Heterocyclic compounds with four - membered rings Heterocyclic compounds with five - membered rings Heterocyclic compounds with six - membered ringsHeterocyclic compounds with five-membered ringsPyrrolP
10、yrrole, or pyrrol, is a heterocyclic aromatic organic compound, a five-membered ring with the formula C4H4NH. Substituted derivatives are also called pyrroles. For example, C4H4NCH3 is N-methylpyrrole. Porphobilinogen is a trisubstituted pyrrole, which is the biosynthetic precursor to many natural p
11、roducts. Pyrroles are components of more complex macrocycles, including the porphyrins of heme, the chlorins and bacteriochlorins of chlorophyll, and porphyrinogens. PyrrolPropertiesPyrrole has very low basicity compared to amines and other aromatic compounds like pyridine, wherin the ring nitrogen
12、is not bonded to a hydrogen atom. This decreased basicity is attributed to the delocalization of the lone pair of electrons of the nitrogen atom in the aromatic ring. Pyrrole is a very weak base with a pKaH of about 4. Protonation results in loss of aromaticity, and is, therefore, unfavorable.Reacti
13、vityBoth NH and CH protons in pyrroles are moderately acidic and can be deprotonated with strong bases such as butyllithium and the metal hydrides. The resulting pyrrolides are nucleophilic. Trapping of the conjugate base with an electrophile (e.g., an alkyl or acyl halide) reveals which sites were
14、deprotonated based on which ring positions actually react as nucleophiles. The product distribution of such a reaction can often be complex and depends on the base used (especially the counterion, such as lithium from butyllithium or sodium from sodium hydride), existing substitution of the pyrrole,
15、 and the electrophile.The resonance contributors of pyrrole provide insight to the reactivity of the compound. Like furan and thiophene, pyrrole is more reactive than benzene towards nucleophilic aromatic substitution because it is able to stabilize the positive charge of the intermediate carbanion. This is because the nitrogen can donate a lone pair into the ring by res
