IntroductionandNamencleture

1、Heterocyclic Chemistry For graduate students ofDepartment of Chemistry血红素和叶绿素血红素和叶绿素靛蓝和马钱子碱（兴奋剂，杀虫剂）靛蓝和马钱子碱（兴奋剂，杀虫剂）百草枯百草枯心痛定心痛定心绞痛心绞痛1.2 Classification and Namencleture（一）分类（一）分类单环单环 含一个杂原子含一个杂原子 ONHSFuranThiophenePyrrole 呋喃呋喃 吡咯吡咯 噻吩噻吩含两个杂原子含两个杂原子 NONNHNSThiazoleOxazolelmidazole噁唑噁唑 咪唑咪唑 噻唑噻唑NONNH

2、NSIsoxazole Pyrazole Isothiazole五元环五元环 含一个杂原子：含一个杂原子： 吡啶吡啶 吡喃吡喃含两个杂原子：含两个杂原子： NNPyrimidinePyridazineNNNNPyrazine哒嗪 嘧啶 吡嗪NO Pyridine Pyran喹啉喹啉 异喹啉异喹啉 蝶啶蝶啶 吖啶吖啶 Pteridine AcridineNNNNHNHIndolePurineCarbazoleNH吲哚吲哚 嘌啉嘌啉 咔唑（咔唑（9-氮芴）氮芴）NNNNNNNQuinolineIsoquinoline命名原则命名原则:1、音译名、音译名 （同音汉字加（同音汉字加“口口”字旁）字旁）

3、ONHSFuranThiophenePyrrole 呋喃呋喃 吡咯吡咯 噻吩噻吩2、环上原子的编号顺序、环上原子的编号顺序 从杂原子开始从杂原子开始 1，2，3，4 不止一个杂原子，按不止一个杂原子，按O，S，N顺序编号顺序编号 取代基位次之和最小原则取代基位次之和最小原则呋喃呋喃(furan)噻吩噻吩(thiophene)吡咯吡咯(pyrrole)实例实例:五元杂环五元杂环SN12345NN12345NN12345HH thiazole噻唑噻唑 pyrazole吡唑吡唑 imidazole咪唑咪唑OCOCH32-乙酰基呋喃SNH5C25-乙基噻唑NNCH3OHN-甲基-2-羟基咪唑NNNH2

4、HPhCO2-氨基-5-苯甲酰基苯并咪唑NHCOOH3-吲哚甲酸五元杂环苯并体系五元杂环苯并体系苯并呋喃苯并呋喃(benzofuran)苯并噻吩苯并噻吩(benzothiophene)苯并吡咯苯并吡咯吲哚吲哚 (indole)吡啶吡啶(pyridine)(pyridine)吡喃吡喃(pyran)(pyran)-吡喃酮吡喃酮(-pyrone)(-pyrone)-吡喃酮吡喃酮(-pyrone)(-pyrone)哒嗪哒嗪(pyridazine(pyridazine) )嘧啶嘧啶(pyrimidine)(pyrimidine)吡嗪吡嗪(pyrazine)(pyrazine)六元杂环六元杂环喹啉喹啉(q

5、uinoline)异喹啉异喹啉(isoquinoline)苯并吡喃苯并吡喃(benzopyran)苯并苯并- -吡喃酮吡喃酮(benzo- -pyrone)嘌呤嘌呤(purine)六元杂环苯并环系六元杂环苯并环系杂环并杂环杂环并杂环色酮色酮chromoneNNNNNNNNN1,2,3-triazineor -triazine连连三三嗪嗪1,2,4-triazineor as-triazine1 1,2 2,4 4- -三三嗪嗪1,3,5-triazineor s-triazine1 1,3 3,5 5- -三三嗪嗪NNNNNN1,2,3-benzotriazineor -phentriazin

6、e连连三三氮氮嗪嗪1 1,2 2,3 3- -苯苯并并三三嗪嗪1 1,2 2,3 3- -三三氮氮萘萘1,2,4-benzotriazineor -phentriazine1 1,2 2,4 4- -苯苯并并三三嗪嗪1 1,2 2,4 4- -三三氮氮萘萘具有特殊名称的杂环具有特殊名称的杂环Replacement nomenclature (table 1) The appropriate carbon ring system is named by the IUPAC rules and the heteroatoms present are inddicated as prefixes.

7、Element valence Prefix O II Oxa S II Thia Se II Selena N III Aza P III Phospha Si IV Sila B III BoraAzabenzene 1.3-diazabenzene Silabenzene 1-aza-4- phosphabenzene Azacyclohexane Oxacyclopentane 1,4-Dithiacyclohexa-2,5-dieneNNNSiHNPNSSOSystematic (Hantzsch Widman) nomenclature for monocyclic compoun

8、ds(Table 2) 1) In this system the names of heterocycles are construted by com- bining prefixes that indicate the heteroatoms present with stems that indicate the ring size, and whether or not it is saturated.O, Te, S2. When two or more different heteroatoms are present, prefixes are in order, O, S,

9、Se, Te, N, P, As, Si, Ge, B. 3. Two or more heteroatoms of the same type are indicated by di, tri, etc. Numbering starts with the heteroatome highest in the above order.NNNOOSONNO NHSNThiireneOxirane1,3-Diazete1,2-Oxazetidine1,3-Dioxolane1,2,4-TriazineThiepaneAzocineONHNNNON1H-Azirine2H-Azirine2H-1,

10、3-Oxazzine6H-1,3-Oxazine3H-AzepineOSNNNNMeNHHNSHNNN2-Furylfuran-2-yl3-Thienylthiophen-3-yl2-pyridylpyridin-2-yll6-Quinolylquinolin-6-yl3-Isoquinolylisoquinolin-3-yl1-MethylpyridiniumPyrrol-1-iumThiazoliumImidazolide1,4-Dihydropyridin-1-ideThe naming of fused ring systems1) Many heterocyclic structur

11、es contain two or more fused ring. Some of these have recognized trivial names but the vast majority have not. The systematic names of fused ring systems are derived by regarding common atoms as belonging to both ring systems.2) Names of the components of the fused system are chosen from the list of

12、 trivial names. The largest component having a recognized name is chosen ( e.g., “indole rather than pyrrole if an indole fragment is present in the polycyclic system). If a monocyclic component dose not have a recognized trivial name, the system name, derived from Tables 1 and 2, is used.3) In a fu

13、sed system made up of two or more seperately named components, one is chosen as the basic component for composite name.4) The second component is added as a prefix to the name of basic component. This prefix is derived by replacing the final ine of name of six-menbered ring system by o or delete le

14、for five- menbered ring system . Thus pyrazine becomes pyrazino .5) Bonds forming the ring system of the basic component are labe- lled a, b, c etc., starting with the side normally numberred 1, 2. The second component are numbered in the nomal way. The site of fused is then indicated by the appropr

15、iate letter and numbers.NNONN+ON12345abcdeImidazo2,1-boxazoleNNNNN12345+NNabcdefImidazo1,5-bpyridazine6) Numbering of the fused system is carried out in independently of the above operations and normally starts at an atom adjacent to a brigehead position, such that heteroatoms are given the lowest p

16、ossible numbers. In ambiguous cases, atoms which appear highest in the table 1 are given the lowest numbers. O II Oxa S II Thia Se II Selena N III Aza P III Phospha Si IV Sila B III BoraSO1) Is there only one component which contains nitrogen ?NOYes: choose this as base componentONBase component is

17、pyrrole2) Is nitrogen absent from all the ring ?NOYes: choose the ring containg a heteroatom which occurshighest in table 11.2Base component is furanIf the ring contain the same heteroatom go to 3.Scheme for deriving the base component of a fused system O II Oxa S II Thia Se II Selena N III Aza P II

18、I Phospha Si IV Sila B III Bora3) Are there more two rings present ?NOYes: choose the component containing the greater number of ringBase component is quinoline4) Are the two rings of diferrent size ?NOYes: choose the larger oneBase component is azepineNNNNO5) Do the rings contain diferrent numbers

19、of heteroatoms ?NOYes: choose the one with the greater numberBase component is isoxazoleNOHNAzepine=氮杂唑NNNN6) Are there diferrences between the unmbers of each kind of heteroatom in the two rings ?NOYes: choose the ring with the greater unmber of atomslisted first in table 11.2NOOBase component is o

20、xazole7) choose as the base component the ring for which the heteroatoms have the lowernumbers(Before fusion).Base component is pyrazoleNONS12344a5677a4H-furano2,3-e-1,2-oxazine8) Numbering of fused ring system must give the all hetroatoms the lowest combined numbers.练习练习2,9-dihydropyrano2,3-bindole

21、pyrano2,3-bindole1.3 Structures and spectroscopic properties of aromatic heterocycles This chapter describes the structures of aromatic heterocycles and gives a brief summary of some physical properties. 1.3.2 Carbocyclic aromatic systems Structures of benzeneStructures of NaphthaleneAromatic resona

22、nce energy 150 117 90 122 68 KJ mol -1杂原子的电负性杂原子的电负性顺序？顺序？1.3.2 Structure of six-membered heteroaromatic systems Structure of pyridineStructure of diazinesStructures of pyridinium and related cationsisoelectronic with benzene The more electronegative oxygen tolerates positive charge much less well t

23、han nitrogen, the pyrylium cation is certainly a less stabilised system than a pyridinium cation.Similar to pyridineStructures of pyridones and pyronesPyridines with an oxygen at either the 2- or 4-position exist predo-minantly as carbonyl tautomers, which are therefore known aspyridones.In the anal

24、ogous oxygen systems, no alternative tautomer is possi-ble; the systems are known as pyrones. Pyrones are less aromatic than pyridones, as can be seen from their tendency to undergo addition reactions , and as would be expected from a consideration of the aromatic contributors, 25 and 27, which have

25、 a positively charged ring heteroatom, oxygen being less easily able to accommodate this requirement.1.3.3 Structure of flve-membered heteroaromatic systems Structure of pyrroleCyclopentadiene, with a pKa of about 14, is much more acidic than a simple diene, just because the resulting anion is reson

26、ance stabilised.Pyrrole is isoelectronic with the cyclopentadienyl anion, but is electrically neutral because of the higher nuclear charge on nitrogen. (氮原子的正电氮原子的正电荷？）荷？）电负性的解释有疑意！电负性的解释有疑意！Structures of azoles The 1,3- and 1,2-azoles, five-membered rings with two hetero atoms, present a fascinatin

27、g combination of hetero atom types - in all cases, one hetero atom must be of the five-membered hetero-cycle (pyrrole, thiophene, furan) type and one of the imine type, as in pyridine; imidazole with two nitrogen atoms illustrates this best.NNHImidazolePyrazole1.3.4 Structures of bicyclic heteroarom

28、atic compounds Structure of QuinolineStructure of Quinolinearomatic rings are disrupted1.3.5 Tautomerism in heterocyclic systems A topic which has attracted an inordinately large research effort over the years is the determination of precise structure of hetero-cyclic molecules which are potentially

29、 tautomeric - the pyridinol/pyridone relationship (sec-tion 1.2.4) is one such situation. In principle, when an oxygen is located on a carbon or to nitrogen, two tautomeric forms can exist; the same is true of amino groups.记住：记住：OH 主要以酮式存在，主要以酮式存在，NH2 主要以氨基形式存在，而主要以氨基形式存在，而SH在六员环以酮式在六员环以酮式，五元环以巯基形式存

30、在。，五元环以巯基形式存在。1.3.6 Ultraviolet/visible (electronic) spectroscopyp p p p* transition 240-260 nmn p p* transition from 270 nm in pyridine to 340 nm in pyridazine The bicyclic azines have much more complex electronic absor-ption, and the n p p* and p p p p* bands overlap; being much more intense, the

31、latter mask the former. The UV spectra of the simple five-membered heteroaromatic systems all show just one medium-to-strong low-wavelength band with no fine structure. Their absorptions have no obvious simila-rity to that of benzene, and no detectable n p p* absorption, not even in the azoles, whic

32、h contain a pyridine-like nitrogen.1.3.7 Nuclear magnetic resonance (NMR) spectroscopy The chemical shifts of protons attached to, and in particular of the carbons in, heterocyclic systems, can be taken as relating to the electron-density at that position, with lower fields correspon-ding to electron-deficient carbons.1.4 Anomeric Effect (异头效应）异头效应）.魏荣宝魏荣宝 张大为张大为 梁梁 娅娅 卢俊瑞卢俊瑞 李红姬李红姬, 有机化学中的异头效应有机化学中的异头效应 有机化学有机化学 2008, 28(10), 1663-1675异头效应要符合以下条件异头效应要符合以下条件: : 一是相互作用的基团要处于反式共平面一是相互作用的基团要处于反式共平面; ; 二是相互作用的轨道能级要接近二是相互作用的轨道能级要接近. . 如当氧的孤对电子轨道与极性如当氧的孤对电子