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1 Alicyclic Chmistry. Lctur 3 Th ovrall strain in cycloalkns can b masurd by th magnitud of th complxation constants with Ag +. Th gratr th angl strain th mor it is rlivd in th π-complx which rducs th π-charactr in th doubl bond and, thrfor, th largr is th quilibrium constant for th formation of th complx: + AgN 3 K Ag + N 3 - K Cycloalkyns In cycloalkyns w ar trying to forc two 180 o angls into th ring so, as in transcyclalkns, th angl strain is larg and th smallst ring which can xist at room tmpratur indfinitly is, again, ight. 180 o 180 o Again, as w saw with trans-cycloalkns, th xtra strain crats unusual ractivity. In acyclic systms, th bas-inducd quilibrium btwn an alkyn and an alln lis havily in favour of th alkyn. For som cycloalkyns this situation is rvrsd: C 2 C bas C 2 Ring Siz: Ratio alln/alkyn:

2 Som of th Strain of rganic Chmistry a) Synthtic Cuban: P. E. Eaton, T. W. Col, J. Am. Chm. Soc., 1964, 86, 962, 3157 Prisman: T. J. Katz, N. Acta, J. Am. Chm. Soc., 1973, 95, 2738 Th only Ttrahdran: G. Mair, S. Prifn,. Schafr, R. Matusch, Angw. Chm. Int. Ed. Eng., 1978, 17, 520 1,1,1-Propllan: K. B. Wibrg, F.. Walkr, J. Am. Chm. Soc., 1982, 104, 5239 Cyclooctadiyn: E. Klostr-Jnsm, J. Linz, Angw. Chm. Int. Ed. Eng., 1973, 12, 671.

3 b) Natural C 3 (C 2 ) 8 (C 2 ) 7 C 2 Strculic acid: J. R. Nunn, J. Chm. Soc., 1952, 313 (C 2 ) n C 2 Alutacnoic acids A(n=5) and B(n=7):. Kogn, T. Kiho, K. Tago, S. Miyamoto, T. Fujioka, N. tsuka, K. Suzuki-Konagai, T. gita, J. Am. Chm. Soc., 2000, 122, β-caryophylln: T. L. Dawson, G. R. Ramag, B. Wilson, J. Chm. Soc., 1951, 3382 R 2 R 1 Nocarzinostatin: K. Edo, M. Mizuyaki, Y. Koida,. Sto, K. Furukata, N. tak, N. Ishida, Ttrahdron Ltt., 1985, 26, 331.

4 Conformational Analysis You hav sn how conformations influnc ractivity in th first yar.g. th E2 limination mchanism rquirs that molcul adopts a conformation such that th dparting groups (usually X) ar anti-priplanar. r w study th gnral ffct of conformation on th kintics of all sorts of ractions in cyclohxan rings whr th phnomnon is much gratr bcaus of th rlativ rigidity of six-mmbrd rings compard to acyclic molculs. Such a study is calld Conformational Analysis. Bfor w look at th kintic sid, howvr, w nd first to considr som thrmodynamic aspcts. 1. Conformations of Cyclohxan Thr ar two limiting (i.. hav a maximum or minimum nrgy) conformations of cyclohxan, th boat and th chair: Enrgy ~21 KJmol -1 Sinc most cyclohxans xist in th chair form rathr than th much highr nrgy boat form, conformational analysis is almost xclusivly applid to substitunts on cyclohxans in th chair conformation. Th simplst substitunt is hydrogn and, in principl, thr ar two typs of hydrogn in cyclohxan dpnding upon thir orintation in spac: C 3 axis axial quatorial

5 Thr ar six hydrogns projcting paralll to a C 3 axis of symmtry through th cntr of th ring (axial) and thr ar six hydrogns which projct around th quator of that axis (quatorial). Thus, in principl, w might xpct to s two lins in an 1 nmr spctrum of cyclohxan. In practic, thr is only on lin bcaus both typs of hydrogn ar rapidly xchanging placs during th tim of th nmr rcording, not by bond clavag but simply by rotations about a numbr of singl C-C bonds, a conformational flxing calld Ring Flipping: x (ax) x (ax) y (q) y (q) x (q) y (ax) Sinc w wish to know th influnc of conformation upon th ractivity of substitunts w now turn to substitutd cyclohxans. r th sam ring flipping can occur so that th substitunt may adopt an axial or an quatorial position: X X In th axial position th two hydrogns (shown) which ar 1,3-rlatd to X com within rpulsiv forc distanc to X and hnc a dstabilising comprssion is st up. This is known as 1,3-Diaxial Comprssion. In th quatorial position th narst nighbours ar th 1,2-quatorial hydrogns which ar pointing away from X. Thus th quilibrium usually lis ovr on th sid of that conformation in which X is in an quatorial position. Th xtnt of this disturbanc will obviously dpnd on th siz of X as th following tabl shows: Group Fr nrgy diffrnc (q/ax) (kj mol-1) Equilibrium Ratio(q:ax) F 1.1 Cl : 1 Br : 1 I : 1 M : 1 Et : 1 ipr : 1 >21.0 >6300 : 1

6 SiM GM SnM PbM gcl 0 1 : 1 Ph : 1 CN 0.7 Ac : 1 C C 2 Et 5.1 (fr) 2.2 (-bond) 3.7 M 2.5 N In conformational analysis w wish to s how th ractivity of a group in an axial position diffrs from th sam group in an quatorial position and, thrfor, w nd to stop ring flipping. n way to do this is to put a trt-butyl group on th ring sinc from th Tabl w can s that this frzs th ring into that conformation in which th t-bu group rmains quatorial. owvr, such ring compounds ar not radily availabl. Altrnativly, w can us a systm known as trans-dcalin in which two six-mmbrd rings ar fusd togthr: A B If w wr to try and ring flip ithr ring A or ring B thos quatorial bonds (markd ) would bcom axial and th rmaining ring would brak (try this on a modl). A naturally occurring and radily availabl sris of compounds containing th transdcalin systm is th Stroids and, historically, it was this group of compounds which providd th tsting ground for conformational analysis.

7 M M β-fac M 1 M For xampl 3β-cholstanol: 6 7 A B α-fac M M M