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`r, Carol Verbeecle
`
`Library of Congress C3(3lOgiIlg-in-PUbliC3{i0n Data
`
`Loudon, G Marc
`Organic clicinisiiy.
`Includes index
`I
`(‘.lieiiiisii\j, Org;inic.
`QD2Sl.2.L68
`I988
`ISBN 0-80S_5-034:5-l
`
`.
`
`.
`-
`
`.‘
`
`87-29996
`
`Permission for pUbl|C2lllOl‘l herein of Sadtler Standard Spectra“ has
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`Copyright © 1988 hy Beniiiniiii/(iiiminings Piihli.~:hiiif2, (‘.()mp:ii1y, Inc.
`© 1984 by .-\(l(lI.\()I1—V~"CS|t_"V l’ul)lisliing, (joiiipiiiiy. Inc.
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`stored in ii fC[I'l€\".il
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`iiicaiis. Cl(‘IC[|'()lllC.
`lH('3L'h'.ll1lCLl[. pliiiiocopyiiig, iL-cording, or
`oiliviwisc. wiilmiit Elk‘ prior written p(fl'lhi\\iU!1 (it the pul3li.<1ici‘
`Pflllltftl in ihi: liniii-(l States of Amcriczi.
`l'[|hli>5|k‘(l .»iii1iili.'iiii‘mi.~l_v
`in (i;iii.igl;i
`
`=\H('.l)l‘.l'Li| ll_!-\'| I
`
`.\“L\‘_
`
`Tlic llciii;iiniii/(Tiiiiiiiiiiigs l’iihli.~liing (:()l1l]‘-;ll1\’_ Inn:
`1".“ S-;iii(| Hill
`l{«i;iLl
`Mciilu l’.||'L. lf.ililui':ii;i 9~i()_’i
`
`Page 2 of 7
`
`

`
`
`
`24.2 Inttociuchon to the Aromatic Hetutocycles
`
`7057
`
`
`
`4 Propose ‘:1 synthesis of the following compound from naphthnienet (The Frie<_iel-
`C1‘21fI>' re:tction cannot be used bee-.tuse it gives :1 mixture of 1~ and 2~;tcetyi—
`i‘iLiphliI'.llt‘nL' that is (iifficttlt to .‘5t']7:ll‘:llC'.)
`
`O\ /CH3
`
`‘/\_ I \
`\, 5 /
`
`‘.2 :‘NTHODUCT/ON TO THE /IFFOMATIC HE
`
`
`
`A. Nomenclature
`
`The mines and stmcturcs of some common aromatic heterocyciic compounds ate
`given in Fig. 24.1. This figure also shows how the rings are numbered in s_vstem:1tic
`nomenciztture.
`In all but 21
`few cases.
`2!
`|1etei'o;itom is given the number 1. (iso-
`quinoline is an exception.) As we see in thiazoie and oxazoie. oxygen and sulfur are
`given :1 lower number than nitrogen when 3 choice exists. Substituent groups are
`given the lowest number consistent with this scheme.
`
`I \
`
`N:
`H
`
`..
`
`
`
`C1130
`
`CVHS
`
`"
`
`NH
`
`3-ethylpyrroie
`
`
`
`5-methoxyindole
`
`t
`
`2-elhylfuran
`
`3-nilrothiophenc
`
`(These are the same rules used in numbering and nanting sziturzited heterocyclit
`coinpoundsz see Secs. 8.1(_I and 23.18.)
`
`Page 3 of 7
`
`

`
`1052 Chapter 24: Chemistry of Naphthalene and the Aromatic Heterocycles
`
`. ——~—..——. to ..
`
`Problems
`
`6 Name the following compounds:
`
`Ca)
`
`I*{
`/
`Br—<_S)—CH3
`
`(b)
`
`Br
`
`N02
`
`(C)
`
`/—\
`1‘?I
`ll
`
`8. Structure and Aromatlclty
`
`The aromatic heterocyclic compounds furan, thiophene. and pyrrole can be wri'
`resonance hybrids, illustrated here for furztn.
`‘ 5
`
`Since separation of charge is present in all but the first structure, the first stru
`considerably more important than the others. Nevertheless, the importance
`other stmctures is evident if we compare the dipole moments of furan and tetra
`furan, a saturated heterocyclic ether.
`
`5 B
`O
`
`dipole moment
`boiling point
`
`tetrahydrofuran
`l.7 D
`67°
`
`I l
`O
`
`furan
`0.7 D
`3l.4°
`
`The dipole moment of tetrahydrofuran is attributable mostly to the bond dipol
`
`oxygen because of its electronegativiry. This same effect is present in fur.'m.,
`addition there is ‘.1 second effect: the resonance delocalization of the oxygen
`
`electrons into the ring shown in Eq. 24.12. This tends to push elettrons aw
`oxygen into the rr-electron system of the ring
`
`/7‘ .
`1/\r>O
`
`titpnlc tnt>mt'nt
`cotilillmlititt of
`(7 ~(') tr-hontls
`
`dipole niomcnl
`contribution 0!"
`7r«electr0n
`(l8|(l(‘:l|l7Ll[ll')n
`
`4.-‘.
`
`nut dipole
`moment ol
`furztn
`
`
`
`‘-"2"""‘-\L"anzxr;§'»:¢vs-.w':§-I::.‘.*x-;‘».1iri=«.aI
`
`Page 4 of 7
`
`

`
` 24.2 Introduction to the Aromatic Heterocyces
`
`T053
`
`
`
`
`
`«-:-me‘.-»»~-tr-'.:«'t,\cr/.v-..«-‘V:
`
`
`
`electron pairs
`
`are pan of the
`1r—system
`
`
`
`P)'I't’o|e
`
`furan
`
`unshared electron pairs ’
`(not in -rr—system)
`
`‘? The configurzttions of the lInSlT.lI'€(l electron [):llI'.'s and
`tare .'?-4.?
`electrons in pyridine. pyrrole, and tumn. The orbit-.tls in each
`‘7i+ 2-electron -msystem -.tre shown in grey, 1r-interactions are .sl1()\XI‘t
`10!‘. Llnshared electron pairs not in the -rr-system are shown in txhite.
`
`in
`
`Because these two effects in furan nearly cancel, furan has a very small dipole mo-
`ruent. We can see the effect of dipole moment on the relative boiling points of tetrahy~
`drofuran and furan.
`Pyridine, like benzene, can be represented by two equivalent neutral resonance
`structures. Three additional st ructures. although involving separation ol cliarge, have
`some importance because they reflect the relative electronegativity of nitrogen.
`
`4-»
`
`/
`
`
`minor contributors
`
`The aromaticity of some heterocyclic compounds was considered in our discus-
`sion of the Htickel /in + 2 mile (Sec. 1S.6D). It is important to understand which
`unshared electron pairs in a heterocyclic compound are part of the 421+ 2 aromatic
`1r-electron system, and which are not. Heteroatoms involved in formal double bonds-
`such as the nitrogen of pyridine—contribute one rrelectron to the six -tr-electron
`aromatic system, just like each of the carbon atoms in the 1r—system. The orbital con-
`taining the unshared electron pair of the pyridine nitrogen is perpendicular to the p
`orbitals of the ring and is therefore not involved in tr-bonding (Fig. 24.52). An un-
`shared electron pair on a heteroatom in a formally allylic position—such as the un-
`
`
`
`Page 5 of 7
`
`

`
`1054 Chapter 24: Chemistry of Naphthalene and the Aromatic Heterocycles
`
`TABLE 24.1 Empirical Resonance Energies of
`Some Aromatic Compounds
`M,
`-,
`».
`-
`V
`v
`-
`..-.
`2 «,-'.--.v.:-rt".
`
`-<
`
`-
`
`,s.w»-.~-:
`
`:.»
`
`r .2,‘ ,_
`
`Resonance ene
`kcaumol
`
`9
`
`Compound
`
`benzene
`
`pyridine
`naplitlialeiie
`
`Resonance energy,
`kcal/moi
`
`Compound
`
`furan
`
`pyrrole
`thiophene
`
`I
`
`shstrecl pair on the nitrogen of pyri-ole~is part of the aroinatic -rrsysteni.
`hyclrogen of pyrrole lies in the plane of the ring (Fig. 2-’i.5b). Tl1eOxy§2,cn of fn
`24.50 contributes one unshared electron pair to the aromatic -rr—electron syst
`the other unshared electron pair occupies 2: position analogous to the liytlro .,
`pyrr0le—in the ring plimtt,
`[)t’1'[)L‘n(llClll2l1‘ to the p ot‘l)it2il.< of the i'in;g,
`I
`‘
`How much .s't;tbility does each l1etei‘c)cyclic. Compound owe to its -.tm:n2tti<:
`ter? In Sec.
`l5.7C we learned that the empirical rmoizaizce L’IIPIg1' can be
`(:'Slll11;l[€
`this st;tl)ility. (Remember that this is the energy 3 compound “tlncsn
`because of its ;u'om;-iticity—th2tt is.
`its aromatic stability.) The empinc;tl rel ..
`energies of benzene, n;-iphthalene. and some heterocyclic compouncls arc
`"
`Table 2-1. 1 . To the extent that rcsonztnce energy 15 it tneusure ol':irom;nic char
`can see that fnrztn has the least ;1l'0l11.’l[lC c|1;ti‘ztt:tc.-r of the licterocyciic minpm
`the table.
`
`‘
`
`ment in each compound.
`
`lions.
`
`8 F;lCl'l til" the lkxllowing cltcmicul .<|1il'Ls' goes with :1 ltyc|mgt:n ;it ttiilmn-I 0l_
`pyriclinc. p_Vl'l'0llLlln'L‘. or py'i‘1‘t>lt:_ l\‘l;l[L'l\ L‘LlL'l1 l.‘ll(_'llllL'2ll shilt with lltt‘ nppm
`.
`.
`-
`»
`.
`-~
`‘
`.
`.
`.7
`lto:tcmt'yt:|ic Coiizpnuntl, ;tmI k‘\l)l;ll1l )'(llII'
`'.ll1.‘w'\\‘t_‘l’. 6 txwl: o (i. ll. .lIlLl 5 ¢~.
`
`c. Basicity and Acidity of the Nitrogen Heterocycles
`
`Basicity l’yl'lt.llllc‘:ll’l(l(|Lll[1Ulll1C.1C[ZIS()l'(llIl;lI‘)'ill'()l1L(llC .tmln<: lust-5: ll‘.<_‘§’ :lI'6‘« "
`;I.s
`l);I$l<_‘ us ;il'lll.ll'lL‘.
`
`Page 6 of 7
`
`

`
`
`
`24.2 introduction to the Aromatic Heterocycles 1055
`
`+ H30’ 7.’ .l
`
`\
`
`/‘
`
`F‘?
`
`\
`
`/
`
`H
`
`+ H30
`
`(24.15)
`
`\
`/
`\ N;
`
`+ H_0+ 7-
`z
`
`pK, = 52
`
`_ / i \
`i
`\/\N/
`I +
`H
`
`pK, = 49
`
`+ H20
`
`(24.10
`)
`
`Pyridine and quinoline are less l)£lSl( than zlllpllilllt.‘ tertiary amines bec;tttse oi" the .«:[r'
`hybridization of their nitrogen unshared electron pairs. (Recall from Sec.
`l-§.7A that
`basicity of an Lll1Sl1‘.-ll‘CLl electron pair decreases with increasing 5—Cl1Zll'fl(‘[€I'.)
`Since pyrrole and indole look like amines, it may come as :1 surprise that (ha
`nitrogens of these two hcteroc,-'cles are not basic zit all! These compounds are proton-
`zltcd only in strong acid, and protomnion occurs on carbon, not nitrogen
`
`r
`—
`
`~
`
`+
`
`H
`
`__
`
`H
`
`Z/H) + H30‘ ..-L ii/J.. 3< 4-» +[n.5< «.»O< + H30
`If
`N
`H
`N
`H
`H
`H
`iii
`H
`H
`J
`l
`l
`
`_.
`
`H
`
`(24.17)
`
`
`
`
`
`We can t.inclerst:tnrl the mnrke(.l ctmtrnst between the hasicities of pyridine and
`pyrrolc by considering the role of nitrogen’s unshared electron pair in the aronmticity
`of each compound (Fig. 2-1.5). Protonation of the pyrrole nitrogen CllSl'Llp[S the aro-
`I11;-1llC six 17-electron systein by taking the nitr0get1's u nsl1;trecl pair "out of circu|;n.i0n. "
`
`+ H,o*
`
`‘
`
`A
`
`\ /
`
`F“
`
`\
`
`;
`
`( 4} + H-,0
`‘
`x H/
`\H
`not arotnatic;
`not observed
`
`(24.|8)
`
`Furthermore, the positive clnirgc in nitrogen-protontited pyrrole cannot be <lc-l0t.‘;tl-
`ized by t'esOn;tm‘e. Altltnttglt [)l'()l()l1Ll[lOll
`til" the cnrlron 0|" pyrrole (Eq, 2.4.17) .ll$()
`disrupts‘ the zirninzttic 1r-electron system. at least the t'c.<nlting (‘;l[lOl1 is l‘C..\'0llLll1CC
`.~.'t:tl)ilizecl. On the other hrincl. protonzttinn til‘ the pyritzlinc llnSll:ll't'£l electmn pnir
`occtim easily hec;tu.<e: this electron pair is not p;u‘t of the 7r-electmn systeiti. llencc
`pi‘0t0n:tti0n oi" this cle.ctt‘on pair (lows not clwettvy ;tmtn:iti«;ity
`lmidztzolt-_ like pyri«;linr.-, is l);l>}lC. .tnc| is pl'Ul()I1(llC(l(()gl\'C'1l C()l1lLl_L‘.;l[(f.lL'l(.l with
`pK_, = (1.9%. Imiclgizoic l1;l.\‘[WUni[l'(>gCl1S:0l1U l\.1.‘~‘ the clcctronic ctxittiqtii-;ttit.>i1oi pyri-
`tlinc‘. but [llL‘0ll1Cl'i.\' lll\'Cll1t‘ tiiti'ogct1 of pyrrnlt-. l’i'titOt1:1titit1 of lll1l(l;l‘/.()l¢3 U\'L'llI'.\ on
`the PYfl(lll1L‘-lll\'L' nitr0gcn—~- the one V\l‘lt).\C electron [T.llt’ is not p;irt oi" the .l1’t>lll;l[l('
`SL‘X[L'[.
`
` -e«Iwt-..-a~u»-»~.t-jltvuu-'.“.~l...,."‘*v‘.‘.g,,»....
`
`Page 7 of 7