P. Scrimin, P. Tecilla, U. Tonellato
FULL PAPER
The two phases were separated and the aqueous one was extracted prepared in water. The reactions were run in a mixture 1:1 DMSO/
twice with 20 ml of CH2Cl2. The combined organic solvents were water (unless otherway stated) at a 0.05 total buffer concen-
dried (Na2SO4) and evaporated to afford 0.15 g (85%) of dimer tration. The pH given is that of the water phase before mixing.
which was used without further purification. Ϫ 1H NMR (CDCl3): Reaction temperature was maintained at 25±0.1°C. Slower reac-
δ ϭ 1.82 (bs, NH); 3.79 (s, 8 H, PhCH2NHCH2), 3.81 (s, 4 H, tions were started by addition of 20 µl of a 1Ϫ2·10Ϫ3 solution
PhCH2NH2), 3.89 (s, 8 H, PyCH2NH), 3.94 (s, 6 H, PhCH2Ph),
of substrate in CH3CN to 2 ml of solution of ligand, additives and
7.11Ϫ7.18 (m, 24 H, Ph), 7.24 Ϫ7.27 (m, 4 H, H3,5Py), 7.57 (t, J ϭ buffer in DMSO/water and faster reactions were started by mixing
7.68 Hz, 2 H, H4Py).
equal volumes of a 2Ϫ4·10Ϫ5 solution of substrate with the solu-
tion of ligands, additives and buffer both prepared in DMSO/water.
The final concentration of substrate was 1Ϫ2·10Ϫ5 and the kine-
tics follow in each case a first order law up to 90% of reaction. The
rate constants were obtained by non linear regression analysis of
the absorbance vs time data (using the software package
Enzfitter[27] or the software package provided with the SF.17MV
stopped-flow work station) and the fit error on the rate constant
was always less than 1%. Reproducibility of different runs were
within 5%.
To the amine thus obtained (0.15 g, 0.17 mmol) dissolved in 40
ml of benzene was added 7 (0.19 g, 0.34 mmol). The reaction mix-
ture was heated at reflux for 5 h distilling azeotropically the water
formed during the reaction. The solvent was then evaporated at
reduced pressure and to the residue was added a suspension of
NaBH4 (0.052 g, 1.37 mmol) in 40 ml of EtOH. After stirring over-
night at room temperature the solvent was evaporated and the resi-
due dissolved in 100 ml of a 8:2 CHCl3/CH3OH mixture and
washed first with a 10% solution of Na2CO3 and then with water.
The evaporation of the dried (Na2SO4) organic solvent afforded a
crude which was purified by column chromatography on Sephadex
LH 60 (CH2Cl2) to give 0.31 g (91.5%) of pure Boc-protected tetra-
[1]
[1a] J. S. Lippard, M. J. Berg, Principles of Bioinorganic Chemis-
try, University Science Books, Mill Valley, CA, 1994, pp.
257Ϫ281. Ϫ [1b] D. E. Wilcox, Chem. Rev. 1996, 96, 2435. Ϫ [1c]
N. Sträter, W. N. Lipscomb, T. Klabunde, B. Krebs, Angew.
Chem. Int. Ed. Eng. 1996, 35, 2024.
1
mer. Ϫ H NMR (CDCl3): δ ϭ 1.41 and 1.45 [2s, 36 H, C(CH3)3];
1.84 (bs, NH), 3.79 (s, 12 H, PhCH2NH), 3.86 and 3.88 (2s, 4 H
and 8 H, PyCH2NH), 3.91 and 3.94 (2s, 4 H and 6 H, PhCH2Ph),
[2]
[2a] J. M. Berg, Acc. Chem. Res. 1995, 28, 14. Ϫ [2b] B. L. Vallee,
4.25 and 4.27 (2s,
4 H, PhCH2NHBoc), 4.41 (bs, 4 H,
D. S. Auld, Acc. Chem. Res. 1993, 26, 543.
PhCH2NBocCH2), 4.48 (bs, 4 H, PyCH2NBoc), 7.06Ϫ7.17 (m, 40
H, Ph), 7.20Ϫ7.27 (m, 8 H, H3,5Py), 7.56 (t, J ϭ 7.68 Hz, 2 H,
H4Py), 7.59 (t, J ϭ 7.68 Hz, 2 H, H4Py).
[3]
P. Scrimin, P. Tecilla, U. Tonellato, G. Valle, A. Veronese, Tetra-
hedron 1995, 51, 527.
[4]
This assumption is based on statistical arguments: in fact the
two reagents are mixed in equimolar amounts and 1H-NMR
analysis of the crude of the polymerization reaction does not
reveal any detectable amount of unreacted dialdehyde or di-
amine.
The previuos protected amine was deprotected using CF3COOH/
CH2Cl2 as described above. The crude was purified by column
chromatography on silica gel (CHCl3/CH3OH/NH4OH, 90:10:1) to
give 0.024 g (10%) of pure tetramer. Ϫ 1H NMR (CDCl3): δ ϭ
1.96 (bs, NH); 3.79 (s, 20 H, PhCH2NH), 3.88 (s, 16 H,
PyCH2NH), 3.93 (s, 10 H, PhCH2Ph), 7.11Ϫ7.19 (m, 40 H, Ph),
7.24 Ϫ7.27 (m, 8 H, H3,5Py), 7.56 (t, J ϭ 7.68 Hz, 4 H, H4Py).
[5]
E. Schnabel, Ann. 1964, 673, 171.
[6]
B. Siegel, R. Breslow, J. Am. Chem. Soc. 1975, 97, 6869.
[7]
Y. Couturier, C. Petitfaux, Bull. Soc. Chim. France 1978, IϪ435.
[8]
P. Scrimin, P. Tecilla, U. Tonellato, T. Vendrame, J. Org. Chem.
1989, 54, 5988.
[9]
K. J. Laidler, P. S. Bunting, The Chemical Kinetics of Enzyme
To the amine thus obtained (0.024 g, 0.016 mmol) dissolved in
Action, 2nd ed., Clarendon, Oxford, 1973; Chapter 11.
[10]
One of the reviewers pointed out whether the interactions in-
6 ml of distilled CH2Cl2 were added 6 (0.016 g, 0.063 mmol) and
˚
volved in the media used in the present study are mainly Lon-
don dispersion forces and do not contain a real hydrophobic
component. His observation is well founded although we like
to mention that rate constants (log kψ) are linear against the
solvophobic scale, Sp, of Abraham (see: M. H. Abraham, L. P.
Grellier, R. A. Mc Gill, J. Chem. Soc., Perkin Trans. 2 1988,
339). No speculation on this point has been made in the text
because of the limited number of solvent mixtures examined.
1g of activated 4-A molecular sieves. The reaction mixture, pro-
tected from moisture, was stirred at room temperature for 20 h.
The reaction mixture was filtered through a short celite pad and
the solvent was evaporated at reduced pressure. To the residue ob-
tained was added a suspension of NaBH4 (0.030 g, 0.8 mmol) in
10 ml of EtOH. After stirring overnight at room temperature the
solvent was evaporated and the residue dissolved in 100 ml of a 8:2
CHCl3/CH3OH mixture and washed first with a 10% solution of
Na2CO3 and then with water. The evaporation of the dried
(Na2SO4) organic solvent afforded 0.024 mg of crude Boc-pro-
tected 5 which was deprotected by treatment with CF3COOH/
CH2Cl2 as described above. The purification of crude oligomer 5
was performed first by by column chromatography on silica gel
(CHCl3/CH3OH/NH4OH, 90:10:1) and then by column chroma-
tography on Sephadex LH 60 (CH2Cl2) to afford 7.5 mg of pure
material as a viscous oil. The small amount of product obtained
[11] [11a]
J. H. Fendler, Membrane Mimetic Chemistry, Wiley, New
[11b]
York, 1982; Chapter 2. Ϫ Metalloaggregates:
K. Ogino, Top. Curr. Chem. 1985, 128, 144. Ϫ
W. Tagaki,
[11c]
P. Scrimin,
[11d]
P. Tecilla, U. Tonellato J. Org. Chem. 1991, 56, 161. Ϫ
R.
Fornasier, P. Scrimin, P. Tecilla, U. Tonellato J. Am. Chem. Soc.
1989, 111, 224. Ϫ [11e] P. Scrimin, P. Tecilla, U. Tonellato, J. Org.
Chem. 1994, 59, 18. Ϫ [11f] P. Scrimin, P. Tecilla, U. Tonellato J.
[11g]
Org. Chem. 1994, 59, 4194. Ϫ
J. G. J. Weijnen, A. Koudijs,
J. F. J. Engbersen J. Chem. Soc., Perkin Trans. 2 1992, 829. Ϫ
[11h] J. G. J. Weijnen, A. Koudijs, J. F. J. Engbersen J. Org. Chem.
1992, 57, 7259. Ϫ [11i] F. M. Menger,L. H. Gan, E. Johnson, D.
H. Durst J. Am. Chem. Soc. 1987, 109, 2800.
[12]
[13]
1
R. Varadaraj, J. Bock, N. Brons, S. Pace, J. Phys. Chem. 1993,
97, 12991 and references therein.
did not allow combustion analysis. Ϫ H NMR (CDCl3): δ ϭ 1.25
(bs, NH); 2.48 (s, 6 H, NCH3), 3.79 (s, 20 H, PhCH2NH), 3.84 (s,
4 H, PyCH2NCH3), 3.88 (s, 20 H, PyCH2NCH2), 3.93 (s, 10 H,
PhCH2Ph), 7.11Ϫ7.16 (m, 40 H, Ph), 7.24 Ϫ7.27 (m, 12 H, H3,5Py),
7.56 (t, J ϭ 7.68 Hz, 6 H, H4Py).
L. G. Ionescu, L. S. Romanesco, F. Nome in Surfactants in
Solution, vol. 2, K. L. Mittal, B. Lindman eds., Plenum, New
York, 1984, pp. 789Ϫ803 and references cited therein.
The ester of γ-amino butanoic acid could not be studied be-
cause of the very fast concurrent cyclization to the correspond-
ing γ-lactam.
[14]
[15]
Kinetic Studies: Slower reactions were followed on a Perkin
Elmer Lambda 5 spectrophotometer equipped with a thermo-
statted cell holder and faster reactions on an Applied Photophysics
SF.17MV stopped flow spectrometer. Solution of the ligands were
prepared in DMSO while metal ions and buffers solutions were
The lack of inhibition by 3.CuII in the case of NipPNP (entry
22) is due to the negligible rate acceleration exerted by CuII ions
with this ester.
[16] [16a]
M. J. Young, D. Wahnon, R. C. Hynes, J. Chin, J. Am.
Chem. Soc. 1995, 117, 9441. Ϫ [16b] R. W. Hay in Comprehensive
1152
Eur. J. Org. Chem. 1998, 1143Ϫ1153