Conclusion

Chapter 8__________________ Conclusion_________________________ 1 67 C onclusion

Eclipsing of N-CH2 bonds in cyclic and acyclic neopentyl amines has been demonstrated, but this phenomenon becomes less important in acyclic tertiary amines with increased branching of the other alkyl groups.

When eclipsed cyclic and acyclic neopentyl amines are protonated eclipsing is no longer the ideal minimum, however cyclic protonated amines with flanking substituents at the 2 and 6 positions still exhibit eclipsing.

Eclipsed bonds are associated with a high rotational barrier and for a number of compounds a novel equilibrium between eclipsed-equatorial and anti-staggered bonds has been established.

Elucidation of the relative importance of ring inversion, nitrogen inversion and bond rotation in cyclic amines has been achieved and nitrogen- inversion coupled with bond rotation in acyclic amines has been discussed.

General Experimental Considerations a) General

Microanalysis were carried out by the Microanalytical section of the Chemistry Department, University College London.

Mass spectra were recorded on a VG7070H mass spectrometer with Finnigan Incos II data system at University College London.

Column Chromatography separations were performed using Merck flash silica (200-400 mesh) as the stationary phase.

Melting points were determined using a Reichert melting point apparatus Molecular Mechanics Calculations MM3 3 3 .3 4 and MMX^I are based on MM3 and MM2 force field respectively.

All experiments using moisture-sensitive reagents were carried out under an atmosphere of dry-nitrogen. All solvents and reagents were obtained from commercial sources and used without further purification. Glassware and syringes for moisture-sensitive reactions were dried in an oven at 130°C.

Chapter 8__________________ Conclusion_________________________ 1 68 Reaction temperatures below 0°C were obtained by cooling acetone with solid carbon dioxide pellets

b) NMR i) General

Routine NMR spectra were recorded using a Varian VXR400(400 MHz) spectrometer, operating at 400MHz for and 100.6MHz for '•^C.

NMR solutions were approximately 0.1 M. A 5mm, switchable variable temperature probe was used for both and ^ H NMR spectra, the spectra being recorded in a pulse Fourier transform mode.

Temperature calibration of NMR samples in a variable temperature experiment was effected using a chemical shift thermometer consisting of an NMR tube containing neat 2-chlorobutane89.

Tetramethylsilane was used as a reference compound in all cases, and chemical shift values given in this work are measured on the S-scale in parts per million (ppm).

The samples for the low temperature spectra were prepared by connecting the NMR tubes, containing C3D6O or CD2CI2 solutions of the compounds to a vacuum line and condensing gaseous (CHF2CI, CHCI2F) by means of acetone in dry ice. The tubes were subsequently sealed and introduced in the pre-cooled probes of the spectrometer equipped with standard variable temperature devices. The measured temperatures are believed to have errors not exceeding ±3°G.

The lineshape analysis has been carried out by means of a program based upon the Bloch equations^G.

ii) Conditions for NOE difference Spectroscopy

NOE difference spectroscopy experiments were carried out on undegassed sample. A typical difference experiment was performed in the following manner: a total of 64 on-resonance, 64 off-resonance transients were

Chapter 8__________________ Conclusion_________________________ 1 69 recorded, a block size of 8 being used with interleaving of the off-resonance and on-resonance spectra.

A pre-irradiation time of approximately 6 seconds was used with the decoupler being gated off during a 3.5 seconds acquisition period.

iii) Conditions for NMR integration of signals

To minimise the errors associated with the NMR integration of a signal, the following precautions were taken.

1) A digital resolution of at least 10 data points/Hz or greater were used. 2) Spectra were essentially noise free, particular care being taken to ensure the spectrum was well phased and possessed a flat baseline.

3) The spectra were derived from unweighted FIDS since resolutions enhancement functions have the effect of suppressing the intensity of broader lines relative to sharper lines.

4) Planimetry rather then electronic integration of a signal was used for determining signal intensity.

c) Crystallography

The crystal structure determination was carried out by Dr D.A.Tocher and was solved by direct methods and developed by using alternate cycles of least- squares refinements and difference-Fourier synthesis. All non-hydrogen atoms were refined anisotropically while hydrogens were placed in idealised positions (C-H 0.96Â) and assigned common isotropic thermal parameters (V=0.08Â2) 2124 reflections (remeasured every 97 scans) showed a 10% of intensity during data collection.

Data were corrected for Lorentz and polarisation effects and for crystal decay. The 1257 unique data with 1>1.5 a (I) were used, and the final least- squares refinement cycle included 189 parameters and did not shift any parameter by more than 0.35 times its standard deviation. R=0.0641, Rw= 0.0687.

______________________________ References___________________________ 1 70

1) J.E.Anderson, J.Chem.Soc., Perkin Trans. 2, 1991, 299.

2) J.E.Anderson and D.G.Watson, J.Am.Chem.Soc., 1992, 114, 1517. 3) J.E.Anderson, J.Chem.Soc., Perkin Trans. 2, 1992, 1343.

4) J.E.Anderson, J.Chem.Soc., Perkin Trans. 2, 1993, 441.

5) J.E.Anderson, J.E.T.Corrie, L.Lunazzi and D.A.Tocher, J.Am.Chem.Soc., 1993, 115, 3493. 6) J.E.Anderson, D.Casarini, J.E.T.Corrie and L.Lunazzi, J.Chem.Soc., Perkin Trans. 2,1993, 1299. 7a) P.W.Rabldeau, K.B.Lipkowitz and R.B.Nachbar Jr, J.Am.Chem.Soc., 1984, 106, 3119. b)R.K.Dhar,

A.Sygula, F.R.Fronczek and P.W.Rabldeau, Tetrahedron., 1992, 48, 9417. c) D.Gordlllo, E.JuarlstI, R.Martinez, R.A.Toscano, P.S.Whlte and E.L.EIIel, J.Am.Chem.Soc., 1992, 114,

2157.

8) J.E.Anderson, ‘Conformational Analysis of Acyclic and Allcycllc Saturated Hydrocarbons’. In "The Chemistry of Alkanes and Cycloalkanes", Patal, 8, Z. Rappoport, Eds.; Wiley, Chichester, 1992; Chapter 3 II. D.

9) J.B.Lambert and Y.TakeuchI, " Cyclic Organonltrogen Stereodynamics" l^ t edition; VCH: New.York (USA), 1992; Pg 169-193, Chapter 7.

10) A.Rauk, C.AIIen and K.MIslow, Angew. Chem., Int. Ed. Engl., 1970, 9, 400. 11) J.M.Lehn, Fortschr.Chem.Forsch., 1970, 15, 311.

12) J.B.Lambert, Top Stereochem., 1971, 6, 19.

13) J.E.Anderson, Fortschr.Chem.Forsch., 1974, 45, 140.

14) C.H.Bushweller In "Acyclic Organonltrogen Stereodynamics", J.B.Lambert and Y.TakeuchI, Ed VCH.New York. 1992. Chapter 1.

______________________________ References___________________________ 171

16) C.H.Bushweller, S.H.FIeischman, G.L.Grady, P.McGoff, C.D.Rithner, J.G.Brennan, M.R.Whalon, R.P.Marcantonio and R.P.Dominque, J.Am.Chem.Soc., 1982, 104, 6224.

17) C.H.Bushweller, W.G.Anderson, P.E.Stevenson, D.L.Burkey and J.W.O'Neil, J.Am.Chem.Soc.,

1974, 96, 3 8 9 2 .

18) C.H.Bushweller, J.W.O'Neil and H.S.BIIofsky, J.Am.Chem.Soc., 1971, 93, 542. 19) J.Reny, C.Y.Wang, C.H.Bushweller and W.G.Anderson, Tetrahedron.Lett., 1975, 503. 20) C.H.Bushweller, C.Y.Wang, J.Reny and M.Z.Lourandos, J.Am.Chem.Soc., 1977, 99, 3938. 21) S.H.FIeischman, M.R.Whalon, C.D.Rithner, G.L.Grady and C.H.Bushweller, Tetrahedron.Lett.,

1982, 23, 4 2 3 3 .

22) C.H.Bushweller and J.W.O'Neil, J.Am.Chem.Soc., 1970, 92, 2159.

23) C.H.Bushweller, C.T.Danehey(Jnr), G.L.Grady and P.R.Bonneau, J.Am.Chem.Soc., 1988, 110,

7269.

24) L.Lunazzi, D.Macciantelli and D.Grossi, Tetrahedron., 1982, 39, 305.

25) D.Casarini, S.Davalli, L.Lunazzi and D.Macciantelli, J.Org.Chem., 1989, 54, 4616. 26) P.A.Berger and C.A.Hobbs, Tetrahedron .Lett., 1978, 1905.

27) C.H.Bushweller, W.G.Anderson, P.E.Stevenson and J.W.O'Neil, J.Am.Chem.Soc., 1975, 97, 4338.

28) J.E.Anderson, D.A.Tocher, D.Casarini and L.Lunazzi, J.Org.Chem., 1991, 56, 1731. 29) J.E.Anderson, D.Casarini and L.Lunazzi, J.Chem.Soc., Perkins Trans .2, 1990, 1791. 30) J.E Anderson, D.Casarini and L.Lunazzi, J.Chem.Soc., Perkins Trans . 2 ,1991, 1431. 31) D.A.Forsth and S.M.Johnson, J.Am.Chem.Soc., 1993, 115, 3364.

______________________________ References___________________________ 1 72

33) N.L.AIIinger, Y.H.Yuh and J.H.Lii, J.Am.Chem.Soc., 1989, 111, 8551. 34) N.L.AIIinger, M.Rahman and J.H.Lii, J.Am.Chem.Soc., 1990, 112, 8293.

35) R.J.Abraham and P.Lofus, “Proton and Carbon 13 NMR Spectroscopy”, John Wiley and Son, New York (1983), P I 66.

36) A.A.Frost and R.G.Pearson, “Kinetics and Mechanism”, John Wiley and Son, New York (1961).

37) H.S.Gutowsky and C.S.Holm, J.Chem.Phys., 1956, 25,1228.

38) D H.Willams and I.Fleming. "Spectroscopic Methods in Organic Chemistry" 3rd edition McGraw-Hill (UK) 1980, PglOO-101.

39) J.A.Schwarcz^ and A.S.Perlin, Can.J.Chem., 1972, 50, 3667.

40) D.E.Dorman, D.Bauer and J.D.Roberts, J.Org.Chem., 1975, 40, 3729.

41) MMX forcefield as in PCMODEL, Serena Software, Bloomington Indiana, see J.J.Gajewski, J.J.Gilbert, K.K.Mckelvey, J.Advances in Molecular Modelling 0/K\ Press, Greenwich, Conn., 1992, Vol 2.

42) U.Berg and J.Sandstrom, "Static and Dynamic Stereochemistry of Alkyl and Analogues Groups" Advances in Organic Chemistry Vol 25, Pg 13, Chapter 3.

43a) F.G.Riddell, J.Chem.Soc. B., 1967, 560.

b) F.G.Riddell and J.M.Lehn, J.Chem.Soc.Comm., 1966, 375.

44) A.R.Katritzky, V.J.Baker, I.J.Ferguson and R.C.Patel, J.Chem.Soc., Perkin Trans. 2 ,1979, 143. 45) V.J.Baker, I.J.Ferguson, A.R.Katritzky,.R.Patel and S.Rahim-Rastgoo, J.Chem.Soc., Perkin Trans.

2, 1979, 377.

46) C.H.Bushweller, M.Z.Lourandos and J.A.Brunelle, J.Am.Chem.Soc., 1974, 96, 1591. 47) A.Bouchemma, P.H.McCabe and G.A.Sim, Acta.Crysta.C., 1990, 46, 674.

______________________________ References___________________________ 1 73

48) F.R.Farmer and J.Hamer, Tetrahedron., 1964, 24, 829.

49) H.S.Gutowsky and P.A.Temussi, J.Am.Chem.Soc., 1967, 89, 4388.

50) J.M.Lehn, F.G.Riddell, B.J.Price and 1.0.Sutherland, J.Chem.Soc. B., 1967, 387.

51) R.P.Duke, R.A.Y.Jones, A.R.Katritzky, R.Scatterwood and F.G.Riddell, J.Chem.Soc., Perkin Trans. 2, 1973, 2109.

52) J.E.Anderson, D.Casarini, A.I.Ijeh, L.Lunazzi and D.A.Tocher, J.Am.Chem.Soc., 1995, 117, 3054. 53) J.E.Anderson, D.Casarini and L.Lunazzi, J.Org.Chem., 1993, 58, 714.

54) D.A.Forsyth and S.M.Johnson, J.Am.Chem.Soc., 1994, 116, 11481.

55a) M.A.Cremonini, L.Lunazzi, G.PIacucci, R.Okasaki and G.Yamameto, J.Am.Chem.Soc., 1 9 9 0 ,112,

2915.

b) E.Juaristi, R.Martinez, R.Mendez, R.A.Toscano, M.Soriana-Garcia, E.L.EIiel, A.Petsom and R.S.GIass, J.Org. Chem., 1987, 52, 3806.

56a) J.Sandstrom “Dynamic N.M.R Spectroscopy to Organic Chemistry” Academic Press New York 1 985.

b) M.Oki “Applications of Dynamic N.M.R Spectroscopy to Organic Chemistry” VCH Publishers Weinheim FRG 1985.

57) F.A.L.Anet, G.N.Chmurny and J.Krane, J.Am.Chem.Soc., 1973, 95, 4423. 58) F.A.L.Anet and J.R. Bourn, J.Am.Chem.Soc., 1967, 89, 760.

59) D.Hofner, S. Les ko and G.Binsch, Org.Magn.Reson., 1978, 11, 179. 60) D.A.Foryth and V.Prapansiri, J.Am.Chem.Soc., 1989, 111, 4548.

______________________________ References___________________________ 1 74

62a) J.J.Delpuech in “Cyclic Organonltrogen Stereodynamics”, J.B.Lambert and Y.TakeuchI, eds., VCH, New York 1992, Chapter 6;

b)P.J.Crowley, M.J.T Robinson and M.G.Ward, J.Chem.Soc.Commun., 1974, 825. c)P.J.Crowley, M.J.T Robinson and M.G.Ward, Tetrahedron., 1977, 33, 915. d)D.C.Appleton, J.McKenna and J.M.Mckenna, J.Am.Chem.Soc., 1976, 98, 292. e)J.McKenna and J.M.Mckenna, J.Chem.Soc. B., 1969, 98, 644.

f)P.J.Crowley, M.J.T Robinson and G.A.Morris, Tetrahedron, lett., 1976, 3575. 63) V.M.gittens, P.J.Heywood and E.Wyn-jones, J.Chem.Soc., Perkin Trans. 2, 1975, 1642. 64a) J.B.Lambert and W.C.OIiver, J.Am.Chem.Soc., 1969, 91, 7776.

b)J.M.Lehn and J.Wagner, Tetrahedron., 1970, 33, 4227. 65) J.M.Lehn and J.Wagner, J.Chem.Soc.Comm., 1970, 414.

66) D.A.Forsyth, W.Zhang and J.A.Hanley, J.Org.Chem., 1996, 61, 1284. 67) J.E.Anderson, D.Casarini, A.I.Ijeh and L.Lunazzi in press.

68) S.F.Nelson and G.R.Weisman, J.Am.Chem.Soc., 1974, 96, 7111. 69a) J.M.Steward, J.Am.Chem.Soc., 1954, 76, 3228.

b) S.F.Nelson and G.R.Weisman, J.Am.Chem.Soc., 1976, 98, 3281. 70) R.C.Fuson, W.E.Parham and L.J.Reed, J.Am.Chem.Soc., 1946, 68, 1239.

71a) A.R.Katritzky, I.J.Ferguson and D.M.Read, J.Chem.Soc. Perkin Trans. 2 ,1977, 818. b)A.R.Katritzky, I.J.Ferguson and D.M.Read, J.Chem.Soc. Comm., 1977, 818. 72) H.Booth and R.U.Lemieux, Canad.J.Chem, 1971, 49, 772.

______________________________ References___________________________ 17 5

73) A.R.Katritzky, I.J.Ferguson, F.M.S.Brito-Palma and L.Angiolini, J.Chem.Soc., Perkin Trans. 2 ,1980, 1746.

74) R.F.Evans, Aust.J.Chem., 1967, 20, 1643. 75) J.Graymore, J.Chem.Soc., 1924, 2283

76) J.E.Anderson, D.Casarini, A.I.Ijeh, C.Storch and L.Lunazzi in press.

77) F.A.L.Anet, I.Yavari, A.R.Katritzky, M.Moreno-Mahas and M.J.T.Robinson, J.Chem.Soc.Comm.,

1976, 399.

78a) F.G.Riddell, E.S.Turner, D.W.H.Rankin and M.R.Todd, J.Chem.Soc.Comm., 1979, 72. (b) F.G.Riddell, E.S.Turner, D.W.H.Rankin and M.R.Todd, J.Mol.Struct, 1981, 71, 171. 79) F.A.L.Anet and I.Yavari, J.Am.Chem.Soc., 1977, 99, 6753.

80a) J.J.Delpuech and M .N.Deschamps, J.Chem.Soc.Comm., 1967, 1188. b) J.J.Delpuech and M .N.Deschamps, Tetrahedron., 1978, 34, 3017. 81) J.K.Becconsall, R.A.Y.Jones and J.McKenna, J.Chem.Soc.Comm., 1965, 1726. 82) J.J.Delpuech and B.Bianchin, Tetrahedron., 1974, 30, 1974.

83) A.M.Haines and M.S.Shandiz, J.Chem.Soc., Perkin Trans. 2, 1989, 359. 84) R.A.Robinson, J.Org.Chem., 1951, 16, 1911.

85) H.C.Brown and P.Hein, J.Am.Chem.Soc., 1964, 86, 3566.

86) S.H.Pine, B.A.Catto and F.G.Yamagishi, J.Org.Chem., 1970, 35, 3663.

87) E.L.EIiel, D.Kendasamy, C-Y.Yen and K.D.Hargrave, J.Am.Chem.Soc., 1980, 102, 3698. 88) J.E.Anderson and A.I.Ijeh, unpublished results.