46 Heterocyclic Compounds, Furan 6-Membered Heterocyclic Compounds : a CO Pyridine Quinoline Isoquinoline Most of the heterocyclic compounds are known by their common names. For naming their the hetero atom is always numbered as |. The carbon atoms next to the hetero atom are imi as the a-carbon atoms and those further away as - and y-carbon atoms. Cte (so N 2 oO H 2-Nitropyrrole 2-Furansulphonic acid SINGLE-RING HETEROCYCLESgen) are sp? hybridised, Th in pyrrole (4 carbons + / nitrogen) J st ugh sag aos arth atomic orbitals of the ive hyogens forming orbitals Veep With ore Fig. 46.1), Allthese c bonds lieJnone Pane. ¢ aes Tat fiso has an unhybridised erie and these a eet ach ring ato sa ori wren plane of o bondsThe p orbitals on at nen chad te ri consis lets he Jone PA role shows aromatic properties or roms Te ing reoutarorbiaT satisfies the Huckel's rule (r= 1 in 4n +2). plorbitals v i Fig. 48.2. Adjacent p orbitals overlap to form the x molecular ‘orbital in pyrrole. H's bonded to carbons are deleted for clarity. Short-Hand Representation, A common short-hand representation of pyrrole is simply pentss with circle inside. The circle represents the x molecular orbital. D = © mma sy H Resonance Structures, According to the resonance theory, pyrrole is considered tot the following five resonance structures, paaaeiatess Biegnsttsred ‘BP 131°C. It tums brown in the « Miscible with ether or ethanol Ttgives electrophilic substi" Tealso undergoes diazotisation °HETEROCYCLIC COMPOUNDS possible for the i attack at 2-post by attack at 2-position, That is, the inte Fe eet rae teen ene ce tyson following equations represents an electrophile. 43 H H . iy pak, sh, a aan. me We Pe Ne 3 H NS W Hq N 4 H Less stable More stable Favoured product ‘Some ofthe important reactions of pyrrole are given below Pe) character. Pyrrole can also act as a weak acid; its acidity is about the same as that of actyiéne. For example, if pyrrole is heated with metallic potassium in n-heptane as solvent, stable potassium pyrrotide is formed ee ee ES N (reiniee see vk (om 236) ( pitti Cho) Putin) Potassium pyrrolide reacts with alkyl halides at 60°C o give N-alkylpyrroes. These on heating to 200°C readily rearrange to C-alkylpyrroles c\ a. l J N Ss das O 8s Henan Raich cy + cHoly el We Pyrrole Perc lee sey/ Pyrrole is used : (1) as acommercial solvent ; (2) for pharmaceuticals. CHO Structure. All ring atoms in furan (4 Carbons + / Oxygen) are sp* hybridised. The ‘orbitals overlap with each other and with the s atomic orbitals of the four hydrogens fornin ‘©-0, and C-H o bonds. All these ¢ bonds lie in one plane. The third sp? orbital on oxy Properties or aromaticity bee" in 4n +2), Furan can be repHETEROCYCLIC COMPOUNDS Preparation. Furan is synthecic., sidan (Cerolysacehaidsy ren 284 fom fray yp ng three steps arc invoice! BY acidchydrolysis of pentosans fi HO au * pM L Oo - (CeHe0,), (HOH), HSV, FV AT! znotxoys oy Hace el HO” So een Se, CHZOH (eembay © Pentosans Aldopentose en, lode I Properties. Furan is a colour Si ( a eo : ether but soluble in most ae ae - nh 4°C, having odour of chloroform. Itis insoluble in 1 of the important () Electrophitie tions. Furan, like pyrrole, reactions at 2-position, (@ Halogenation Substitution hee eactions of furan are given below + undergoes electrophilic substitution oO ) ‘Br j ©) Niteation pone gp, 2Bometuran ae ee { \ (CHsC0},0 = ©D + wo 2858 Ono, Furan 2-Nitrofuran (©) Sulphonation Rae do Vow So, Prine, avons ° — ~e Furan 2-Furansulphonie acid (@) Friedel-Crafts Acylation eee ° 9. ° l \ tl it > f\_! + CH;—C—O—C—CH, 4S oo C= CH © Thiophene colourless liquid, bp 84°C, having odour very similar to that of benzene, ‘soluble in ethanol, ether, and acetone 0 ‘Thus thiophene undergoes the electrophilic conditions. Thiophene undergoes chlorination, nitration,> A TEXTBOOK OF ORGANIC ¢ O\-no, + 1,0 s (Nisan O # HNOs —* = 2.Nitrothiophene @ Thiophene (© Sulphonation n a SO3H + H,0 | Dene & a iIphor Thiophene 2-Triophenesulphonic ; (@ Friedel-Crafts Aeylation e } ig we Oko Pec, + CHy-C—Cl pan ls ; es v A pcsythiophene A Om Foealphrarisation, Catalytic reduction‘of thiophene with nickel catalyst results in therem form n-butane, “a Hp Me CHsCHsCH:CHs + NIS re n-Butane duction. On reduction with sodium amalgam and ethanol, it is converted tetrahydrothiophenesy— ) (Sx st) are ie 3) we ‘Thiophene er ehpstionhore, {eabenzene, CsHsN i coal tar (0.1%) and in the distillate from bones. (bone oil) and has been produce Strially ‘sources. ‘Struefur®All ring atoms in pyridine (5 extbons + 7 nitrogen) are sp” hybridised. Two of the ‘orbitals on each atom overlap with each othero form the C-C and CN o bonds. The thirdHETEROCYCLIC COMPOUNDS on each carbon overlaps with, on nitrogen is completely i nitrogen lone pair. All bo; Each ri ‘an orbital from hydro illed. The aia onto form the CH o bonds. The third sp? orbital eee Pat Of electrons in this orbital is referred to as the PPaTidine lie in one plane and al bond, angles are 120°. ‘unhybridised p orbital ene P orbital containing an electron. These p Plane containing (a) bonds. The lateral overlap of the p orbitals Hae cttining ix electrons, One half thin MO le above Because the resulting x molecular rb roi shows aromatic ropes ranean s the Huckel's rl eee 'srule (n= 1 in 4n+2), ye Fig. 46.6. Adjacent p orbitals overlap to form the x molecular orbital in pyridine. H's bonded to carbon atoms are not shown for clarity and Representation, A.common short-hand representation of pyridines simply hexagon, tha-ircfe inside. The circle represents the delocalised molecular orbital O = O Representations of Pyridine Resonance Structures, According tothe resonance theory, pyridine is considered to be hybrid of the following resonance structures. Ge Qe.) —O.—©. -Pyridit a [-fad (bp upto 170°C). Itcan lation Soal-tar. Pyridine occurs inthe fight oil fraction of coal-tab (bp upto 170°C). I bei en oomee it with dilute sulphuric acid. This removes a = Bes = es én yer as soluble sulphates. The acid-layer is then treated with sodium re ee en pre wen tiquid ‘separates. Pyridine is. ‘obtained from this oily liquid by fractional distil ae Prepgration. Pyridine may be obtained : ) /From acrolein by the following steps : CHs " Nis, OY KaGr20r/H, =cH—-CHO —, > (0) 2. CH=CH: a GS a ‘Acrolein Piacnone ee | on 20 __ eign GmA TEXTBOOK C unmonia, and formaldehyde dimethylaceal inh, Bee CD (a dindereyty auc=cH + NHy * CH(OCHs)2 “500 ; woh Formaldehyde : dimethylacetal Pyridine °C, having a characteristic unplea: «- catourless liquid, bp 115.5°C, having acl SN odo, is. Pyriine isa colours its, Some ofthe important reactions Of pyridine are, and most organi Itis soluble in = 5 sicler ; Formation fo Salts. Pyridine is basic (pK, =8.75). It reacts with sy, | H Ch Pyridine Pyridinium chloride XPLANATION. The reason for the basic character of pyridine is that the nitrogen lone electrons are in sp? hybrid orbital and are not involved in the formation of the delocalised x mo! orbital. It is readily available for the formati ‘bond with proton. ir v Tone pair in Portal a) ede hal ja” ne (less basic) e the nitrogen lone pair electrons in pyrrole r= are not available for the format © Lone pair in ‘sp? orbital ( a3, inte are byt EY; my HETEROCYCLIC ComPoUNoS . : @) Electrophitic Subs . Be PPA Sates RectonsPyrdng Pasion ony nde vious cnie Undergoes electrophilic substi reactions Do intermediate with only to me VOD 12 poston fr ice 4) are posable forthe MPO esoance conan Or Peston in pyridine ado . en i b , " Attack at 3-Position a H 2 Z H 5! A i E E Ola ert — 4] «oy ir ! N N N Sw " More sable Faveaned product ‘ (@ Nitration ae S.Ntropyridine ‘ (6) Sulphonation SO3H QO aoe N -Pyridinesulphonic acid Pyridine 3-Pyridinesuip Br ; QO. oO N ae ‘3-Bromopyridine 3 Pyridine pyri @)_Nucleophilc Substitution Reaction Pyridine undergoes nucleophilic substitution reactions : 0 at position in pyridine leads to an intermediate with ea the nucleophile at 2-position (or 4-position) also {Attack at 4-position resembles attack at isblocked). Nu inthe following equations (© Bromination 59-400 csHETEROCYCLIC COMPOUNDS Properties, (? pica). Indole fo Curiously enough, in dilute soluige jasmine and orange blends. Indole 8 Colourtes. at fowery odour andes ble into wat 4 strong fecal odour. icon Used in perfumery for preparing leohol and ether, (Chemical), Chemically, itresembles pyrrole. Itis basic and, / yrole.Itis basic and gives electrophilic substation reactions such as nitration, sulphonation, and halogenation at 3-position. Its derivative Indoxyl exhibve tautomerism and behaves as a phenol. = Ba y-ohe H (keto form) A solution of indoxyl in aqueous sodium hydroxide is readily oxidised by air to the insoluble bu dye, indigo. INDIGO, Indigotin, C\gHyyN:02 ~ Tn sed by man. At onetime itwas obtained in large quantities in India from the indigo plant (Indigofera tinctoria). The dye takes its name from the Greek word Indikos, meaning ‘of India’. The preparation of indigo has now been entirely superseded by synth Processes. Structure of Indigo (Indi fe molecular formula C,H oO:N2- ice of Two Isatin Units. Oxidation of indigo with nitric acid yields two molecules of isatin, CyeHyoO2Ne + 210) IndigoA TEXTBOOK OF ORGANIC cy, sy 786 de oftwo isatin units joined through 2073 cx, | | sule is made of t | This ints hatin ce of indigo would be I or II, each of which Pem; double bond. The two | formation of istin by oxidative cleavage Isatin ole [Ss0 oO c=0 Nae” N’ Ny H H af Isatin 68) Isatin Units joined through C-2. On treatment with dilute sodium hydroxide, india anthranilic acid and indoxyl-2-aldehyde. The formation of these products can be explained only by structure |, G=0 0=¢ 2140, pa YY ——e fect” JO N : N 8 HN’ Indoxyl-2-aldehyde Anthranilic acid This proves that indigo has structure I. 4) Synthetic Proof, Thestructure of indigo was confirmed by synthesis from isatin accom by Baeyer (1872). : 0 C=O PCs C: Oo 5 OSE. 26 H N e (enol form) {satin 4 C=0 _o, Z ————» i 2 ¢ q ZncHscOOn” CH, 2H,0)" c: ey sep athe baba caiisilNois snore Ne KS i 1 BO MH sce aetaacs sat aller a aS | ce ani dete poxsse pCi ee, (8) Indigo is Tr Indigo, in which the two i i isin units are joined by a carbon- Phihalimide Me Anthranic ace Vi0s a Properties, Indigo is a dark blue powder with a copper lustre, mp 390°C. Its insoluble in water, ther and sleohol When reduced with sodium dithionite (NeyS,0,)in the preseneof sodium hydroxide, indigo is transformed into Leucoindigo (or Indigo White). The blue colour is regenerated when this solution is exposed to air, or more quickly by using an oxidising agent such as sodium perborate. ONa ° en Na Leucoindigo sodium salt (colourless; soluble) Dyeing with Indigo. Indigo is suspended in ts eayed fsimmersed in it and then exposed 10 ocked inthe fibre:1p texTBOOK OF ORGANIC on 768 inmaking inks. Blue jeans dyed within, s deep blue and i Uses, Indigo is used to dye extiles dee? a craze of the younger folk. pena ing fused with a pyridine ring in 2,3-posi a benzene ri Fichone CH in 2-position has been replaced by N, Th QUING ANE 25-Be heterocycle having fered as naphthalene in W name of quinoline is 1~ oO S or om it. It is prepared 1 occurs in eoaltar Say with other bases My can be isolated fi frequently by synthesis, Skraups Spnthesis,A mixture oF aniline, glyeerol and sulphuric acid is heated in the p “The reaction being exothermic tends to be vic a mild oxidising agent such as nitrobenzene. FeSO, is also added as moderator. CH,OH i H,SO/FeSOy O GO. == 00 NH CH,OH a Aniline Glycerol Quinoline MECHANISM. The Skraups reaction is believed to proceed by the following steps :(1) G dehydrates with H,$O, o form aerolein ; (2) Acrolein undergoes 1,4-addition with anil resulting B-anilinopropionaldchyde eyclizes to dihydroquinoline ; (4) Dihydroquinoline is oxidise: quinoline, while nitrobenzene is reduced to aniline which is reused. OH OH OH t HpS04, i CHy—CH-GH, “= CH,=CH—CHO + 2H,0HETEROCYCLIC COMPOUNDS Quinoline ie more Hci Quinoline hydrochloride ce of Sos OO + CH —> O Ne I CH; NMethy/quinolnium iodide Q) Electrophilie Substitution Reactions. t undergoes electrophilic substitution reactions in the benzene ring and notin the more resistant pyridine ring. The electrophile preferably attacks positions 8and5. Quinoline cerol ) The ed to NO, 8 and §-Nitroquinoline SO3H 8- and 5-Quinolinesulphonic acid sn Reactions. Quinoline readily gives nucleophilic substitution NaN oO. + NaH 2 WO NHe 2-Aminoquinoline i oO. + UH ‘CoHs ‘pPhenyiquinoline— A TEXTBOOK OF ORGANIC CHEMI s: 5. etrahy droquinoline. The benzene rn, (4) Reduction. Quinoline is easily reduced to yield 1,2,3.4 being more resistant is not reduced. 4 er CL) N 1 4,2,3,4-Tetrahydroquinoline +1 or ZCH,COOH. This reduction can also be carried with Sn/HC! or Zn/CHy BRE yitis pn (5) Oxidation. On vigorous oxidation with alkaline potassium permanganate, it yields pyridin. dicarboxylic acid. Sy kno, ~ 2C02 + I J on a N’ Quinoiine Pyridine-2,3-dicarboxylic acid (Quinolinic acid) On heating, quinolinic acid decarboxylates to yield pyridine-3 sarboxylic acid (nicotinic aci ‘ses, Quinoline is used : (1) as a high-boiling basic solvent in organic reactions - (2) in ‘manufacture of pharmaceuticals, dyes, and insecticides, Structure, (1) Ithas the molecular formula CsH;N. (2) It Gives the electrophilic substitution reactions like benzene and forms salts with a ids like pyridine. ) On oxidation with alkaline potaisium permanganate to form 2,3-pyridinedicarboxylic ac From analogy of oxidation of naphthalene to form phthalic acid, it ie argued that quinoline is made ‘benzene ring fused with pyridine in 2,3-positions. CO am Naphthalene Phihaicase” Z~_ COOH | ce | N Quinoline ie enon 2.3-Pyridinecarboxylic acid ° Quinolineie HETEROCYCLIC COMPOUNDS a ©) (Quinoline is considered s resonance hybrid of thre ca nical f canonical forms, pF 6 -CO-— co -00 (©, Quinoline is a 107 electron which proves its aromatic character. eas nzopyridine, 2. Resonance hybrid el rule (n= 2 in 4n + 2) system like naphthalene. It obeys Huck fzanaphthalene we ee OD. - OO. 8 at e Tsoquinoline is found as a part of the total ‘structure of many alkaloids. Bischler-Bapieralski Sy inthesis. Isoquinoline is easily prepared from 2-phenylethylamine by the following steps. 5 He te : S, e aoe Sa t NH 4 ee 7 d . H H peor N-Formy.2- (eno! form) Aged re foe phenylethylamine ea a Pda ON a 3,4-Dihy pai e Isoquinoline = Properties. areas colourless solid or liquid, mp 23°C, bp 243°C. Itis insoluble in water, at ee cpr cosy eens quolie Onxiaion wih emangun, olin jedicarboxylic acid. acid and 3,4-pyriit pea Macc. Ch ‘COOH Hooc Phthalic acid 3,4-Pytidinedicarboxylic acid examaron QUESTIONS oon. Pe i: Panjab BSc, 1998 » Mad