Cyclam synthesis

H. Stephan, A. Rohrich, S. Noll, J. Steinbach, R. Kirchner, and J. Seidel, Carbohydratation of 1,4,8,11-tetraazacyclotetradecane (cyclam) Synthesis and binding properties toward concanavalin A, Tetrahedron Lett., 48 (2007) 8834-8838. 

C. A. Boswell, C. A. S. Regino, K. E. Baidoo, K. J. Wong, D. E. Milenic, J. A. Kelley, C. C. Lai, M. W. Brechbiel, Bioorg. Med. Chem. 2009,17,548-552. A novel side-bridged hybrid phosphonate/acetate pendant cyclam synthesis, characterization, and Cu small animal PET imaging. 

Aza macrocycles have also been used as templating agents in the formation of zinc and other metal cation-containing aluminophosphates via hydrothermal synthesis.705 The zeolite-like structures have been formed in the presence of cyclam- and hexaaza-based macrocycles. 

Ni(cyclam)]2+ was shown to be an efficient electrocatalyst for the intramolecular cyclization-carboxylation of allyl or propargyl-2-haloaryl ethers,200 and for the synthesis of cyclic carbonates from epoxides and carbon dioxide.201... 

They presented the first synthesis of cobalt(III) cyclam in the absence of oxygen. Generally, for such a procedure, molecular oxygen is used to convert cobalt(II) to cobalt(III). However, because there are systems for which oxygen is undesirable, preparation of cobalt(III) cyclam from a refluxing mixture of tri(acetylacetonato)cobalt(III) and cyclam is a significant accomplishment. 

Cyclam, or 1,4,8,11-tetraazacyclotetradecane, was first synthesised, inadvertently, by van Alphen in 1937 through the reaction of 1,3 bis (2 aminoethyl)-aminopropane with 1,3 dibromopropane. The first major studies of the ligand by Bosnich et al. used X-ray crystallography to elucidate different conformations of the metal complexes of the macrocycle.27 Their synthesis was similar to van Alphen s procedure, but did not involve a template method and as a result yields were unimpressive. They showed that five out of the possible ten different metal-complex conformers exist in the solid-state (Figure 3.51). 

The standard synthesis for cyclam was developed by Barefield and Wagner in 1976.29 They used similar starting materials to the van Alphen procedure but the cyclisation yield is improved through the use of a nickel (II) template. Glyoxal completes the macrocycle by a Schiff base condensation reaction. The resulting imine functionalities are reduced with sodium borohydride to leave the complexed macrocycle. The metal ion is then removed by reaction with cyanide and the free ligand extracted with chloroform (Scheme 3.19). Yields are typically in the region of 60%. 

Scheme 5.2 Synthesis of tetra (hydroxy propyl) cyclam (5.21) via Michael addition followed by reduction, and X-ray crystal structure of its 1 1 copper(II) acetate complex.19...

The synthesis of 11 (an analogue of 7 in which its 12-membered cyclen had been replaced by 14-membered cyclam rings) was reported in 1998 using the tri-N-tosylamide derivative of cyclam and l,3,5-tris(bromomethyl)benzene as precursors [24], The trinuclear Hg(II) derivative was shown to selectively recognise and bind a tripodal tris(histidine) ligand in which the three (S)-histidines are 12 A apart. The system was seen as a model for peptide recognition. 

Uses Cyclohexylamine is a strong inflammable liquid with a fish-like odor. It has many applications in both household and industrial processing (e.g., a corrosion inhibitor in water boilers, the synthesis of pesticides, dry-cleaning soaps, the manufacture of plasticizers, textile chemicals, cyclamates (artificial sweeteners), dyestuffs).41,49... 

Irradiation of manganese azides derived from Mn(III) porphyrin, cyclam, and polyamide complexes represents one of the earliest methods reported for the preparation of nitrido manganese complexes (Eq. (40)) [50], Additional methods have become available for the synthesis of manganese nitrides that utilize ammonia in combination with oxidants such as Cl2, PhIO, NaCIO, and NBS (Eq. (41)) [51-53]. Employing these methods, the manganese nitrides incorporating porphyrin, phath-locyanine, cyclam, salen, and bidentate Schiff base complexes have been documen-... 

Lang DR, Davies JA, Lopes LGF, et al. A controlled NO-releasing compound synthesis, molecular structure, spectroscopy, electrochemistry, and chemical reactivity of R,R,5 )5 -fra s-[RuCl(NO)(cyclam)]5+ (1,4,8,11-tetraazacyclotetradecane). Inorg Chem. 2000 39 2294. 

One of the simplest examples of a nitrogen-containing macrocycle is cyclam (XLV), which was synthesized with a 3% yield from the condensation of l,3-bis(2 -aminoethylamino)propane and 1,3-dibromo-ethane in alcoholic KOH at high dilution (18). A more recent synthesis,... 

Fig. 6 Template synthesis of [Nin(cyclam)]2+ from linear 3.2.3-tet 3 and its demetallation to give the uncomplexed cyclam ligand. Steps i-iv are described in the text...

This chapter does not cover cyclic amides and peptides, since their number would enormously expand this text. They are reviewed only if they serve as reaction intermediates during synthesis of cyclic amines. In addition, metal ions complexation will be presented in required minimum, for example, if it serves for template formation during ring synthesis or as a main topic in some application. In this chapter, most of the sections deal with the literature data for all cycle types, except Section 14.11.6, which focuses mainly on chemistry of cyclen and cyclam and their analogs and derivatives. In Section 14.11.8, we give only a brief overview of the utilizations and provide a reader with reviews where more detailed information may be found. 

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