Bimacrocyclic Pyridines and 1,8-Naphthyridines: Basicities and Application in Base Catalysis
Received: 27 May 2014
Accepted after revision: 12 June 2014
18 July 2014 (online)
Di-α-substituted N-heterocycles such as 2,6-halogenopyridines or 2,7-dichloro-1,8-naphthyridines can be coupled with 2,6-bis(alkenyloxy) substituted areneboronic acids. The resulting tetraenes are then cyclized by ring-closing metathesis to give bimacrocyclic concave pyridines or concave 1,8-naphthyridines. The relative basicity of the concave N-heterocycles was measured and their activity and selectivity was tested in the base-catalyzed addition of alcohols to diphenylketene.
- 1 Concave Reagents, part 65. Part 64: Reimers T, Haberhauer G, Benkhäuser C, Schmidtchen FP, Lützen A, Lüning U. Eur. J. Org. Chem. 2013; 7556
- 2a Steed JW, Atwood JL. Supramolecular Chemistry . 2nd ed. John Wiley & Sons; Chichester: 2009
- 2b Supramolecular Chemistry, From Molecules to Nanomaterials . Vol. 1–8. Steed JW, Gale PA. John Wiley & Sons; Chichester: 2012
- 3a Lehn J.-M. Supramolecular Chemistry: Concepts and Perspectives. Wiley-VCH; Weinheim: 1995
- 3b Vögtle F. Supramolekulare Chemie . Teubner; Stuttgart: 1989
- 4 See textbooks of biochemistry, for example: Voet D, Voet JG, Pratt CW. Lehrbuch der Biochemie . Wiley-VCH; Weinheim: 2002
- 5 Concave geometry is a major factor in host–guest recognition. Most molecules are ‘potato shaped’ and thus convex. To be complementary to such a guest molecule, host molecules have to possess concave areas. For references, see books on supramolecular chemistry such as refs. 2, 6 and 8.
- 6a Lehn J.-M. Supramolecular Chemistry . Wiley-VCH; Weinheim: 1995
- 6b Davis F, Higson S. Macrocycles . John Wiley & Sons; Chichester: 2011
- 7 Lüning U. Liebigs Ann. Chem. 1987; 949
- 8 Lüning U. Concave Reagents . In Molecular Encapsulation . Brinker UH, Mieusset J.-L. John Wiley & Sons; New York: 2010
- 9 Lüning U, Müller M, Gelbert M, Peters K, v. Schnering HG, Keller M. Chem. Ber. 1994; 127: 2297 ; and cited references
- 10 Ross H, Lüning U. Tetrahedron Lett. 1997; 38: 4539
- 11 Lüning U, Liebig T. Eur. J. Org. Chem. 2012; 1346
- 12 Lüning U, Baumgartner H, Wangnick C. Tetrahedron 1996; 52: 599 ; and cited references
- 13 Winkelmann O, Lüning U. Supramolecular Chemistry 2009; 21: 223 ; and cited references
- 14 For unprecedented hemiacetal formation by NHC organocatalysis, see: Winkelmann O, Näther C, Lüning U. Org. Biomol. Chem. 2009; 7: 553
- 15 For exclusive 2-acylation of a glucose derivative catalyzed by a concave pyridine, see: Petersen S, Lüning U. Eur. J. Org. Chem. 1999; 847
- 16 Lüning U, Baumstark R, Schyja W. Tetrahedron Lett. 1993; 34: 5063
- 17 Liebig T, Abbass M, Lüning U. Eur. J. Org. Chem. 2007; 972
- 18 Lüning U, Fahrenkrug F. Eur. J. Org. Chem. 2004; 3119
- 19a Koch V, Schnatterer S. Synthesis 1990; 497
- 19b Bojarska-Dahlig H, Swirska A. Roczniki Chemii 1953; 27: 258 ; Chem. Abstr. 1954, 48, 6439i
- 20 Lüning U, Abbass M, Fahrenkrug F. Eur. J. Org. Chem. 2002; 3294
- 21 Mangini A, Colonna M. Gazz. Chim. Ital. 1942; 72: 190
- 22 Ehlers P, Petrosyan A, Ghochikyan TV, Saghyan AS, Neubauer A, Lochbrunner S, Langer P. Synlett 2013; 359
- 23 Stoltenberg D, Näther C, Meyer H, Machay S, Lüthje S, Lüning U. Synthesis 2012; 3095
- 24 Lüning U, Baumstark R, Schyja W. Liebigs Ann. Chem. 1991; 999
- 25a Schyja W, Petersen S, Lüning U. Liebigs Ann. 1996; 2009
- 25b Petersen S, Lüning U. Eur. J. Org. Chem. 1999; 847 ; and cited references
- 25c Lüning U, Hacker W. J. Prakt. Chem. 1999; 341: 662 ; and cited references
- 26 A remarkable change in basicity due to different solvation has been found for 2,6-dialkylpyridines. Di-tert-butyl-pyridine is considerably less basic then other dialkyl-pyridines. See refs. 27 and 28.
- 27 Brown, H. C.; Kanner, B. J. Am. Chem. Soc. 1953, 75, 3865; pK a (in H2O–EtOH 50:50, 25 °C): 2,6-dimethylpyridine: 5.77, 2,6-diisopropylpyridine: 5.34, 2,6-di-tert-butyl-pyridine: 3.58.
- 28 Heintz A, Wandschneider D, Lüning U, Marczak W. Fluid Phase Equilibria 2006; 248: 123
- 29 pK a values are logarithms of the equilibrium constants of the dissociation of acids (including protonated bases) in water. The water concentration of 55.5 M is part of the K a values resulting in acid constants K a with the dimension of M. Thus, all tabled pK a values are water-based and calculated from M concentrations.
- 30 Izutsu K. Acid-base dissociation constants in dipolar aprotic solvents, IUPAC chemical data series, no. 35. Blackwell; Oxford: 1990
- 31 Thymol blue is blue only in strongly basic media when it is deprotonated to the dianionic form. In the described titration, the equilibrium between the neutral red form and the yellow mono-anion was measured by UV/Vis spectroscopy.
- 32 Lüning U, Baumstark R, Peters K, v. Schnering HG. Liebigs Ann. Chem. 1990; 129
- 33a Perrin DD. Dissociation constants of organic bases in aqueous solution. Butterworths; London: 1965
- 33b Oae S, Kadoma Y. Can. J. Chem. 1986; 64: 1184
- 34 Saturated bimacrocycle 13a and unsaturated precursor 11a possess the same number of carbon atoms in the chains between the bridgeheads. However, due to the geometry of the double bond, the Z-unsaturated chains are slightly shorter. Therefore, the unsaturated mixture 11a was studied because it contains, in the mixture, the smallest bimacrocycle(s).