Compounds of amine-substituted cyclic amines: synthesis and structures

Keywords: aldehyde, amine, azamacrocycles, coordinated ligands, coordination compounds, crystal structures, cyclic amines, isomerism, reactions of nitroalkanes.

Cyclic tetra-amines with C-amine substituents are of interest because of the potentially increased denticity of the macrocyclic ligand and the variety of configurations and coordination modes possible. An amine substituent on the central C-atom of a six-membered chelate ring segment of a coordinated cyclic amine in the usual chair conformation cannot readily coordinate. If this chelate ring flexes to a boat conformation the amine can coordinate with relatively little additional ligand strain, resulting for cyclam-6,13-diamines in possible hexadentate coordination. For usually non-labile metal-ions, such as Co^III or Cr^III, the coordinated amine substituents are more labile than the cyclam secondary amine groups and can be displaced by other ligands, forming cations with penta- and tetradentate coordination by the cyclic amine ligand. For metal ions which are usually labile to substitution, such as Ni^II, Cu^II or Zn^II, the secondary amine groups of cyclic amines are much less labile than those of acyclic amine compounds because of their inclusion within the ring structure, but substituent amine donors remain labile, introducing additional aspects to the coordination chemistry.^[1,2]

Amine substituted tetra-aza-macrocycles can be prepared by conventional syntheses, but metal-ion mediated condensation reactions give easier access to a variety of such ligands. These reactions generally include amine–carbonyl condensations involving imine formation steps. The Ni^II and Cu^II ions are usually the most effective ‘mediators’ for such reactions, as they form strong, but labile, metal–nitrogen bonds, combined with flexible coordination numbers and geometries, which facilitate such reactions. Reactions of bis-diamine compounds of Cu^II or Ni^II with formaldehyde and a nitro alkane, RNO₂, form products with acyclic tetradentate ligands, with the diamines linked by a –NH–CH₂–C(R,NO₂)–CH₂–NH– group. The formation of two such links leads to a tetraaza macrocyclic ligand with two nitro substituents. Similar reactions for acyclic tetraamine Cu^II or Ni^II cations lead to aza-macrocycles with one nitro-substituent.^[3] Reduction of these nitro substituents forms cyclic tetra amine cations with amine substituents (see Scheme 1).

Scheme 1.  Showing reaction of [M(en)₂]²⁺ and [M(3,7-diaza-nonane-1,9-diamine)]²⁺, M = Cu²⁺, Ni²⁺, with nitroethane and formaldehyde in basic solution to form the (nitro, methyl)-substituted cyclic tetraamine cation, for which reduction of the nitro-group(s) form (amine, methyl)-substituted cyclic tetra-amine cations.

trans-6,13-Dimethyl-1,4,8,11-tetraazacyclotetradeca-6,13-diamine (diam) is probably the most-studied amine-substituted cyclic amine, largely because of its ready synthesis via reactions of bis(ethane-1,2-diamine)-Cu^II or -Ni^II with formaldehyde and nitroethane. Analogous compounds with larger ring sizes are similarly prepared from longer chain diamines and the alkyl substituent pattern can be changed by using substituted diamines or other nitro alkanes. Similar reactions of linear tetra-amine compounds of Ni^II or Cu^II lead to mono-(nitro, alkyl)-substituted macrocyclic tetra-amines, for which reduction of the nitro groups forms mono-(amino, alkyl)-substituted cyclic amines.

Compounds of these amino-substituted cyclic-amines, homologues and analogues, have been prepared with a variety of transition-metal ions, using methods appropriate for the amine chemistry of each metal ion. Compounds of diam have been reported for V^IV, Cr^III, Fe^II, Fe^III, Co^II, Co^III, Ni^II, Cu^II, Zn^II, Rh^III, Pd^II, Pt^II, Pt^IV, Cd^II, Pb^II and Hg^II.

This Review covers the preparations and properties of compounds of amine-substituted cyclic amines formed via nitroalkane-aldehyde condensations of metal-ion amine compounds, and such compounds with the amine substituents chemically modified. Structures of such compounds included in the Cambridge Crystallographic Database are listed and representative figures of the different structural types shown. In many cases compounds of the azamacrocycles discussed were synthesised for purposes specific to a research project, focussing on some aspect, such as electrochemistry, reaction kinetics or spectroscopy, but such aspects are not covered.

Research into the preparations and properties of the compounds described in this Review began during a period of sabbatical leave which I spent with Alan Sargeson in the Chemistry Department of the Australian National University in Canberra, August 1980–May 1981.

Alan Sargeson and his group developed the facile synthesis of metal ion clathrochelate compounds by reactions of tris(ethane-1,2-diamine) compounds of M^III metal ions, with formaldehyde and ammonia, which form N(CH₂–N–)₃ capped clathrochelate ligands, and by their reaction with formaldehyde and nitromethane, which form C(NO₂){(CH₂–N–)}₃ capped clathrochelate ligands^[4–8], which could be reduced to form the amine substituted cations (see Scheme 2).

Scheme 2.  Synthesis of clathrochelate ligand cations by reaction of [M(en)₃)]³⁺ with formaldehyde and nitromethane and subsequent reduction of the nitro groups.

I attempted to extend these reactions to diamine compounds of the labile Ni^II and Cu^II ions. Facile reactions occurred, but gave complex and, as yet, uncharacterised products. Substituting the di-basic carbon acid nitroethane for tri-basic nitromethane was an obvious strategy change, with the potential of forming macrocyclic products by linking diamines with C(Me,NO₂){(CH₂–N–)}₂ groups.

Reactions of [Ni(en)₂]²⁺ and [Cu(en)₂]²⁺ salts with nitroethane and formaldehyde, in refluxing methanol, with triethylamine as base, occurred rapidly, forming products which crystallised readily, and this encouraged continued studies. Compounds with the macrocyclic ligand with the two diamine residues doubly linked, [M(dino)]²⁺ (dino = 6,13-dimethyl-6,13-dinitro-1,4,8,11-tetraazacyclotetrdecane), were isolated (hereafter ‘1,4,8,11-tetraazacyclotetradecane’ will be represented in formulae by ‘cyclam’).

Bis(nitro,methyl) compounds of 16- and 18-ring membered macrocycles were similarly formed from propane-1,3-diamine and butane-1,4-diamine compounds, respectively, though yields were lower, with extensive polymer formation. Homologues were formed from C-methyl-substituted diamines or with other nitro alkanes. Similar reactions for Cu^II and Ni^II compounds of linear tetra-amines led to compounds of mono-(nitro,methyl)-substituted macrocyclic compounds. Copper(ii) is usually the most successful ‘mediating’ metal ion, although the reactions also occur for nickel(ii), palladium(ii), platinum(ii) and gold(iii) diamine compounds, with Pd^II most effective for the larger ring compounds.^[3]

At this stage, I returned to the Victoria University of Wellington in New Zealand. Studies of these reactions continued in Canberra and Wellington. Geoffrey Lawrance moved to the University of Newcastle and continued the studies with PhD student Paul Bernhardt, who later moved to the University of Queensland, where he established a fourth group studying these compounds.

The dino macrocycle occurs as geometric isomers, with the two nitro-substituents oriented to opposite sides of the cyclam ring, anti- or trans-dino, or with them oriented to the same side, syn- or cis-dino. The reaction of [Cu(en)₂]–(NO₃)₂ or –(ClO₄) with nitroethane and paraformaldehyde (or aqueous formaldehyde added drop-wise) in refluxing methanol, made basic with triethylamine, forms acyclic [Cu(nelin)]²⁺ and macrocyclic [Cu(trans-dino)]²⁺ and [Cu(cis-dino)]²⁺ salts which co-crystallised. The nelin and trans/cis-dino salts can be separated by crystallisation or by chromatography. Relative yields of the acyclic and macrocyclic products depend on reaction conditions, which can be optimised to produce predominantly one or the other – with yields of up to 70% for [Cu(trans/cis-dino)](NO₃)₂. Chromatography of the [Cu(trans/cis-dino)]²⁺ ion showed two closely running bands which could not effectively be separated, indicating the presence, later confirmed, of both [Cu(trans-dino)]²⁺ and [Cu(cis-dino)]²⁺ isomers.^[9]

Reaction of [Cu(en)₂]²⁺ (or [Cu(pn)₂]²⁺, [Cu(propane-1,3-diamine)₂]²⁺ or [Cu(trans-cyclohexane-1,2-diamine)₂]²⁺ with formaldehyde and a nitroalkane in the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate form the same nitro-substituted cyclic tetraamines in similar yields to reaction in the usual alcohol solvents, with less acyclic by-products. Yields were higher for the 16-membered ring compound formed with propane-1,3-diamine.^[10]

Similar reaction of [Ni(en)₂]²⁺ salts, (usually [{Ni(en)₂}₂-µCl₂]Cl₂, ‘Ni(en)₂Cl₂’), with nitroethane, formaldehyde (or paraformaldehyde) and base in refluxing methanol, formed yellow singlet ground state (sgs) [Ni(dino)]Cl₂ which crystallised in ~90% yield, with no indications of the formation of significant amounts of acyclic ligand compounds.^[11,12]

The possible reduction of the nitro groups to form amine-substituted cyclic tetra-amine compounds was an obvious extension of these studies. Reduction of the nitro-groups of the [M(trans-dino)]²⁺ or [M(cis-dino)]²⁺ cations form the trans- or cis-isomers of [M(6,13-dimethyl-cyclam-6,13-diamine)]²⁺ cations, labelled here as diam and cis-diam, respectively, elsewhere as diammac and cis-diammac.

The group in Canberra, led by Geoffrey Lawrance, focussing on the Cu^II compounds, found that the nitro groups of the mixture of products formed by reaction of [Cu(en)₂](NO₃)₂ with nitroethane and formaldehyde were reduced by Zn, Zn/Hg or Sn in acid (usually by Zn/HCl) to form transient Cu^II amine cations, which demetalated to deposit Cu metal and leave protonated amines in solution. Addition of Cu^II nitrate and base to this resulting solution reformed the [Cu(amine)]²⁺ cations. Chromatography, using a Sephadex C25 column, eluting with NaCl solution, resulted in the isolation of five bands, the last two close-running. The first band contained unreacted starting material or readily hydrolysed compound(s). The second band gave crystals of aqua-(1,3-bis(2-aminoethyl)-5-ammonio-5-methyl-1,3-diazacyclohexane)copper(ii) perchlorate, labelled as [Cu(badcH)(OH₂)](ClO₄)₃·3H₂O, FANFIJ, and the third gave crystals of (5-ammonio-5-methyl-3,7-diazanonane-1,9-diamine)copper(ii) perchlorate hydrate, FASWAX, both derived from reduction of [Cu(nelin)]²⁺.

The fourth band gave crystals of trans-[Cu(H₂diam-IIIaa-N4)(OClO₃)₂](ClO₄)₂·6H₂O (labels defined below), FANFEF, in ~31% yield. Crystals isolated from the fifth band in ~15% yield were assigned as [Cu(cis-diam)](ClO₄)₂·2H₂O, although isolation of the pure cis-isomer proved to be difficult^[9] (see Scheme 3).

Scheme 3.  Reaction of [Cu(en)₂]²⁺ with nitroethane and formaldehyde to form acyclic [Cu(nelin)]²⁺ and macrocyclic [Cu(trans-dino)]²⁺ and [Cu(cis-dino)]²⁺. Reduction of the nitro-functions with Zn/HCl and isolation of Cu^II compounds of amine reduction products. Also, reaction of [Cu(2-aminomethyl-pyridine)₂]²⁺ with nitroethane and formaldehyde and reaction of the resultant [Cu(2-methyl-2-nitro-N,N′-bis(pyridine-2-yl-methyl)propane-1,3-diamine)]²⁺ with Zn/HCl.

The [Cu(diam)]²⁺ ion was also formed by an unanticipated reaction when [Cu(2-methyl-2-nitro-N,N′-bis(pyridine-2-yl-methyl)propane-1,3-diamine)]²⁺ was reduced with Zn/HCl, the resulting amine reacted with Cu²⁺ and the product isolated as trans-[Cu(diam-IIIbb-N4)(OClO₃)]ClO₄, DUMGIB^[13] (see Scheme 3).

Meanwhile, in Wellington, Asoskamali Siriwardena^[11] and I focussed on the reduction of the [Ni(trans/cis-dino)]²⁺ cation.

The nitro groups of [Ni(trans/cis-dino)]Cl₂ are not reduced by Zn/HCl and addition of NaBH₄ to a solution causes precipitation of unreduced hydroborate salts. They are reduced by hydrogenation at ambient temperatures in water, using Raney nickel catalyst, typically taking ~8 h at 800 psi, or several days at 50 psi hydrogen pressure.^[11,12]

Evaporation of the reduction solution resulted in a purple gum which was extracted with hot ethanol, giving a purple solution, and leaving residual blue-violet solid. Evaporation of the ethanol solution led to crystallisation of [Ni^#(diam-III-N6)]Cl₂·6H₂O (the label Ni^# indicating triplet ground state, tgs, Ni^II). Acidification of the ethanol extract with HCl caused crystallisation of trans-[Ni^#(H₂diam-III-N4)Cl(OH₂)]Cl₃·3H₂O, KELVUT.^[14] The residual solid crystallised from ice-water/propan-2-ol as trans-[Ni^#(diam-I-N5)(OH₂)]Cl₂·0.5H₂O, which recrystallised from dilute perchloric acid as grey–green trans-[Ni^#(Hdiam-I-N5)Cl](ClO₄)₂·H₂O, PEHXEF.^[12]

Hydrogenation in water formed the [Ni(diam-I)]²⁺ and [Ni(diam-III)]²⁺ products in variable but approximately equal proportions. The proportion of the [Ni(diam-I)]²⁺ isomer formed decreased for reduction in acidic (1 mol dm⁻³ HCl) solution, or in aqueous ammonia solution, or with higher hydrogen pressures.^[11]

Evaporation of the final filtrates from the preparation left a gum, from which a hygroscopic compound of composition [Ni(H₂diam)]Cl₄·xH₂O was isolated by addition of propan-2-ol.^[11] With hindsight this was probably the cis-diam isomer, formed by reduction of [Ni(cis-dino)]²⁺ (see discussion in Compounds of Nickel(ii) with cis-diam, below).

Modifications of the procedure described in Reduction of the nitro substituents of (6,13-dimethyl-6,13-dinitro-cyclam)copper(ii) cations were used to isolate trans- and cis-diam. The mixed [Cu(trans/cis-dino)]²⁺ salt was reduced with Zn/HCl and the resulting solution of [H₆(trans-diam]⁶⁺ and [H₆(cis-diam]⁶⁺ reacted with Cu²⁺ and base. The resulting [Cu(trans-diam)]²⁺ and [Cu(cis-diam)]²⁺ ions were separated by chromatography into four bands, each with distinctive Cu^II d–d spectra. Each isolated band was reduced with Zn/HCl and the resulting amines isolated by chromatography, in overall quantitative yield. The amine isolated from bands 1, 2 and 4 was identified by ¹H NMR spectra as diam and that from band 3 as cis-diam. The isomers were isolated as the salts [H₆diam)]Cl₆·2H₂O and [H₆-cis-diam)]Cl₆·2.5H₂O in ~3:1 proportions.^[15,16]

The diam was released from trans-[Ni^#(H₂diam-III)(OH₂)₂]Cl₄ by heating with conc. HCl in a sealed tube at 110°C, until the purple colour of the Ni^II compound completely faded, taking ~2 days. The [H₆diam]Cl₆·2H₂O was filtered off and washed with conc. HCl/ethanol until free of Ni²⁺. Alternatively, the diam was released by reaction with 4 molar proportions of KCN in water at 100°C taking ~8 h for the purple colour of the [Ni^#(diam)]²⁺ cation to completely fade. The K₂[Ni(CN)₄] was filtered off from the cold solution, the filtrate evaporated to dryness and the amine extracted from the residue with CH₃Cl or CH₂Cl₂.^[12]

The free amines were prepared by reacting the hexa-hydrochloride salts with NaOH in ethanol, filtering off the precipitated NaCl, evaporating the filtrate to dryness, extracting the amine from the residue with CH₂Cl₂ and isolating it as diam·3.5H₂O^[12] or cis-diam·2H₂O.^[15,16]

The amines were also prepared from the hydrochloride salts by using an anion exchange column, with the amine solution used directly, or evaporated and the amine extracted from the residue with CH₂Cl₂.

Hexa-, tetra- or di-protonated salts of diam crystallise from aqueous solution, depending on the acidity and anions present. See Table 1 for reported structures.^[17–21]

Table 1.  Compounds with structures listed in the CCDC database^A.

Analytical results for samples of the amines and salts have indicated variable hydration numbers, which probably depend on crystallisation conditions or subsequent desiccation. Hydration numbers for the amines and salts will here generally be omitted in descriptions of preparations.

The protonation constants, log K_H, of diam, measured by pH titration of [H₆(diam)]⁶⁺ in 0.1 mol dm⁻³ NaClO₄ at 25°C are: 11.2(1), 9.7(1), 6.2(1) and 5.3(1), with the remaining two constants too small to measure in water;^[12] other reported values are: 11.0, 9.9, 6.3, 5.5^[22] and 11.0, 10.0, 6.2, 5.5, ~1.5.^[40] Values for cis-diam are: 10.6, 9.7, 6.3, 5.4, ~2.7.^[40]

The four secondary amine groups of coordinated cyclam are chiral centres, which can occur in five configurations I–V,^[53] see Scheme 4, and the same configurations occur for coordinated diam and cis-diam, with the 6,13-(methyl, amine) substituents giving rise to additional isomeric possibilities.

Scheme 4.  Configurations of coordinated cyclam (wedges indicate NH groups).

Diam (and cis-diam) can coordinate to metal ions by the four secondary-amine cyclam N-atoms, labelled here as diam-N4, or also by one (diam-N5) or both (diam-N6) primary-amine substituents. Uncoordinated amine substituents can be free or protonated, labelled as Hdiam⁺ or H₂diam²⁺.

Distinct configurations are possible for coordinated diam, arising from the orientation of the substituents.^[49] For a six-membered chelate ring of diam in the usual chair conformation, the amine substituent can be equatorially oriented (configuration a) or axially oriented (configuration b); neither is positioned suitably for coordination. If the chelate ring flexes into a boat conformation, a previously equatorially oriented amine substituent (a) becomes axially oriented and able to coordinate with minor distortion of the macrocycle conformation, while a previously axially oriented (b) amine becomes equatorially oriented and still unable to coordinate (see Scheme 5).

Scheme 5.  Interconversion of [M(diam-IIIaa-N4)] and [M(diam-IIIaa-N6] configurations, and inability of [M(diam-IIIbb-N4)] to form [M(diam-IIIbb-N6)].

For diam coordinated in configuration IIIaa, both amine substituents coordinate for configuration diam-IIIaa-N6, one for diam-IIIaa-N5 or neither for diam-IIIaa-N4 – or variants with uncoordinated substituent amine groups protonated.

For configuration diam-IIIbb, neither substituent can coordinate, so only diam-IIIbb-N4 is possible. Since most diam-III compounds have the IIIaa configuration, the aa configuration will usually be assumed and the aa label omitted.

For cations with configurations diam-Iaa or diam Iab, one substituent amine can coordinate on the side of the N₄ plane opposite to the four NH groups and for configuration diam-Ibb only diam-Ibb-N4 is possible. Since all reported structures have configuration Iab, the ab label will be assumed.

For cis-diam, all reported structures, other than two with Cu^II, have configuration cis-diam-Vaa-N6, so the aa label will be assumed.

The cis/trans geometrical configuration of diam is fixed during the [M(dino)]²⁺ synthesis. The cyclam chiral and a/b geometrical configurations of coordinated diam and cis-diam are determined during coordination. Interconversion of cyclam configurations requires inversion at cyclam NH centres, which can occur in basic solution, but is usually inhibited in acid solution. Interconversion of substituent aa/bb configurations requires inversion at all four cyclam NH centres and has not been reported. The IIIbb configuration for diam compounds has been observed only for Cu^II, Pd^II and Pt^II, but occurs frequently for compounds of diam with modified amine substituents. The IIIab configuration has been observed for compounds with modified amino substituents (see Compounds of diam, monam (and homologues) with modified amine substituents, below).

Compounds are discussed in the order of metal ions: Zn–V, Cd–Mo, Pb–Hg.

Formation constants (log K) at 298 K in 0.05 mol dm⁻³ KCl or KNO₃ for diam, cis-diam have been reported for Zn^II; 15.0, 16.1, Cd^II; 10.6, 12.1 and Hg^II; 10.5, 12.2. Pb^II: 10.8, 11.8, with values for cis-diam consistently the higher.^[22,40]

X-Ray crystallographic studies have been essential to disentangling the configurational isomerism of coordinated diam. Table 1 lists compounds of diam, cis-diam and homologues, with structures in the Cambridge Crystallographic Centre Data base. Distinguishing between Hdiam-IIIaa-N4 and Hdiam-IIIab-N4 or Hdiam-Iaa-N4 and Hdiam-Iab-N4 structures depends on assignment of CH₃ and NH₃⁺ groups, which may be difficult for disordered structures or for poor diffraction data sets.

Structures of cations of compounds of different metal ions with the same coordination modes are generally similar, and protonation of uncoordinated amine substituents usually makes little difference to the overall structure of the cation. Figs 1–4 show representative examples of Ni^II cations in each of the most common coordination modes: [Ni^#(diam-III-N6]²⁺, PEHWOO (Fig. 1), trans-[Ni^#(Hdiam-I-N5)Cl]²⁺, PEHXEF (Fig. 2), trans-[Ni^#(H₂diam-III-N4)Cl(OH₂)]Cl₃·3H₂O, KELVUT (Fig. 3) and cis-[Ni^#(cis-diam-V-N6)]²⁺, MASRIH (Fig. 4). Figures shown for other cations display distinctive strutural features.

Fig. 1.  The cation of [Ni^#(diam-IIIaa-N6)]Cl₂·6H₂O, PEHWOO,^[12] drawn from the CIF by using ORTEP-3.2,^[23] with probability ellipsoids at 30% probability, with H(C) atoms omitted for clarity. Other structural figures were similarly produced.

Fig. 2.  The cation of trans-[Ni^#(Hdiam-Iab-N5)Cl](ClO₄)₂, PEHXEF.^[12]

Fig. 3.  The cation of trans-[Ni^#(H₂diam-IIIaa-N4)Cl(OH₂)]Cl₃·3H₂O, KELVUT.^[14]

Fig. 4.  The cation of cis-[Ni^#(cis-diam-V-N6)](ClO₄)₂·2H₂O, MASRIH.^[50]

[Zn(OH₂)₆[(ClO₄)₂ reacts rapidly in water with diam, or a diam salt plus base, to form [Zn(diam-III-N6)]²⁺, which was isolated as [Zn(diam-III-N6)](ClO₄)₂, VISSUL.^[22] [Zn(diam-III-N4)(OS₂O₅)₂], KENPUO^[19] crystallised from a concentrated aqueous solution of dithionate.

[Zn(diam-III-N₄)(OH₂)₂]ZnCl₄ crystallised when HCl and propan-2-ol were added to a solution of diam and ZnCl₂ in 1:2 mole proportions. Mixing hot aqueous solutions of ZnCl₂ and excess diam caused immediate precipitation of a compound of composition Zn₃·diam·Cl₅·OH, which recrystallised unchanged from dilute HCl.^[11]

Titration of [Zn(diam)]²⁺ with acid enabled calculation of the protonation constants and distribution of protonated species as a function of pH (measurements in 0.5 mol dm⁻³ KCl at 298 K). The [Zn(diam)]²⁺ ion is slowly demetalated in dilute acid solution at ambient temperatures.^[22]

The compound cis-[Zn(cis-diam-V-N6](ClO₄)₂, MASRON^[50] (isomorphous with the Ni^II analogue, MASRIH) was prepared by reaction of cis-diam with Zn²⁺.

The formation kinetics of the reaction of diam with Cu²⁺ in water, between pH 0 and 5.5^[54] and in strongly alkaline solution,^[55] have been reported.

The acid dissociation rates for [Cu(H₂diam-III-N4)]²⁺ were measured spectrophotometrically in HClO₄/NaClO₄, ionic strength 2 mol dm⁻³. The first order rate constants observed in 0.2, 0.6, 1.0 and 2.0 mol dm⁻³ HClO₄ solutions were 1.3(5), 1.3(3), 1.3(3) and 1.2(6) × 10⁻⁹ s⁻¹ at 50°C, respectively, and 7.3, 8.0, 7.2 and 7.5 × 10⁻⁹ s⁻¹, respectively, at 70°C. The rate constant in HCl/NaCl (2 mol dm⁻³) at 70°C was 6.5 × 10⁻⁹ s⁻¹. The independence of the rate on the H⁺ concentration indicates that the rate determining step is intramolecular for [Cu(H₂diam)]²⁺.^[11]

[H₆diam]Cl₆·2H₂O in basic solution reacts rapidly with Cu²⁺ to form three isomeric [Cu(diam)]²⁺ ions which were isolated by chromatography in approximately equal proportions, as trans-[Cu(diam-IIIbb-N4)(OH₂)₂](ClO₄)₂, ROMWAR, Fig. 5 (which also crystallised as trans-[Cu(diam-IIIbb-N4)](ClO₄)₂, DUMGIB), [Cu(H₂diam-IIIaa-N4)(OClO₃)₂](ClO₄)₂·2H₂O, ROMWEV (which also crystallised as trans-[Cu(H₂diam-IIIaa-N4)(OClO₃)₂](ClO₄)₂·6H₂O, FANFEF), similar to KELVUT, Fig. 3, and trans-[Cu(diam-I-N5)(OClO₃)]ClO₄, ROMWIZ, Fig. 6.^[49]

Fig. 5.  The cation of trans-[Cu(diam-IIIbb-N4)(OH₂)₂](ClO₄)₂, ROMWAR.

Fig. 6.  The cation of trans-[Cu(diam-I-N5)(OClO₃]ClO₄, ROMWIZ, with coordinated O of ClO₄ shown.

Other Cu^II compounds of diam prepared, but not structurally characterised, include [Cu(H₂diam)]−Cl₄·3H₂O, −(ClO₄)₄, [Cu(diam)]−Cl₂·4H₂O, −(ClO₄)₂·2.5H₂O and –(ClO₄)₂·4H₂O.^[11]

Reaction of Cu²⁺ with [cis-H₆diam]Cl₆·2.5H₂O formed two cations, which were similarly isolated by chromatography in approximately equal proportions, as trans-[Cu(cis-diam-I-N5)(OClO₃)]ClO₄, ROMWOF, Fig. 7 and trans-[Cu(cis-H₂diam-III-N4)(OClO₃)₂](ClO₄)₂, ROMWUL (with NH₃⁺/CH₃ disorder).^[49]

All reported [Cu(diam)] structures have the four cyclam nitrogen atoms in planar coordination, crystallising from basic solution with the amine substituents unprotonated, or from acid solution with the substituents protonated. Reported structures usually have perchlorate ions or water molecules weakly coordinated in the tetragonal sites. The two Cu^II cis-diam compounds are the only structurally characterised cis-diam compounds with other than the cis-diam-Vaa-N6 configuration and [Cu(cis-diam-Iab-N5)(OClO₃)]ClO₄ is the only reported compound of cis-diam with N5 coordination (although the bond to the amine substituent is long at 2.323(4) Å).

Reaction of a Ni^II salt with diam, or with a diam salt and base, rapidly forms [Ni^#(diam-III-N6)]²⁺ and lilac coloured [Ni^#(diam-III-N6)]²⁺ salts crystallise from basic solution. [Ni^#(diam-III-N6)](ClO₄)₂·H₂O, FEBZUH,^[27] FEBZUH10^[12], Ni^#(diam-III-N6)]ZnCl₄·1.5H₂O, PEHWUU,^[12] [Ni^#(diam-III-N6)]Cl₂·6H₂O, PEHWOO^[12] and [Ni^#(diam-III-N6)]·Ni(CN)₄^[11] were prepared.

The protonation constants, pK_a, for [Ni^#(diam-III-N6)]²⁺ in 2 mol dm⁻³ NaClO₄ at 25°C are 4.5(1), 4.0(1), so the amine substituents are protonated in acid solution.^[12] In weakly acidic solution yellow sgs [Ni(H₂diam-III-N₄)]²⁺ and blue tgs trans-[Ni^#(H₂diam-III-N₄)(OH)₂]⁴⁺ cations exist in equilibrium, with the sgs form increasingly predominating with higher concentrations of electrolytes, particularly perchlorate or iodide. Sgs [Ni(H₂diam-III-N₄)](ClO₄)₄, PEHWII^[12] and tgs trans-[Ni^#(H₂diam-III-N4)Cl(OH₂)]Cl₃·2H₂O, KELVUT,^[14] trans-[Ni^#(H₂diam-III-N4)(OH₂)₂]SO₄·5H₂O (and 2H₂O) were prepared.^[11] The amine substituents of [Ni^#(diam-III-N6)]²⁺ are displaced by thiocyanate, with trans-[Ni^#(diam-III-N4)(NCS)₂], PEHXAB,^[12] crystallising from neutral and trans-[Ni^#(H₂diam-III-N4)(NCS)₂](NCS)₂·0.5H₂O from acid solution, and by cyanide, but not by azide, or amine ligands. A compound of unknown structure crystallised with oxalate and no reaction occurred with pentane-2,4-dionate.^[12]

The protonation constants, pK_a, for trans-[Ni^#(diam-I-N5)(OH₂)]²⁺ in 2 mol dm⁻³ NaClO₄ at 25°C are 4.94(2), 2.4(5), so cations are protonated in weakly acid solution.^[12] Compounds prepared in neutral solutions were: trans-[Ni^#(diam-I-N5)(OH₂)]Cl₂·0.5H₂O, trans-[Ni^#(diam-I-N5)(OH₂)]Cl·ClO₄, trans-[Ni^#(diam-I-N5)(OH₂)]ZnCl₄·H₂O, trans-[Ni^#(diam-I-N5)(ONO)]ClO₄·0.5H₂O and trans-[Ni^#(diam-I-N5)(CN)]Cl·0.5H₂O. From weakly acidic solution trans-[Ni^#(Hdiam-I-N5)Cl](ClO₄)₂·H₂O, PEHXEF and from a strongly acidic solution [Ni^#(H₂diam-I-N4)](ClO₄)₄·2.5H₂O crystallised. Most compounds crystallised poorly.^[11,12]

In aqueous solution the [Ni(diam-I)]²⁺ cation slowly isomerises to [Ni(diam-III)]²⁺. The rate constant for isomerisation of trans-[Ni^#(diam-I-N5)(OH₂)]Cl₂·0.5H₂O, in 2 mol dm⁻³ aqueous NaCl at 25°C, at the self-established pH of 2.3, is 5.0(5) × 10⁻⁵ s⁻¹, this rate increasing in both more acidic and more basic solution.^[12]

The [Ni(diam-I)]²⁺ cation is also slowly demetalated in acid solution, the combined rate constant for loss of [Ni(H₂diam-I)]⁴⁺ at 50°C, in 2 mol dm⁻³ NaCl, by isomerisation and demetalation is ~2.4 × 10⁻⁴·[H⁺] s⁻¹.^[12]

Reaction of [Ni(OH₂)₆]Cl₂ with [cis-H₆diam)]Cl₆ in basic solution forms the purple cis-octahedral cation, isolated as cis-[Ni^#(cis-diam-V-N6)](ClO₄)₂, MASRIH (Fig. 6).^[50]

Hygroscopic material of composition [Ni(H₂diam)]Cl₄·xH₂O, isolated under acidic conditions from the residues from the hydrogenation of [Ni(dino)],^[11] was probably a cis-diam compound, but as no structures have been reported it will be labelled as ‘diam?’.

Orange/yellow coloured (sgs) compounds of composition [Ni(H₂diam?-N4)](ClO₄)₄, [Ni(H₂diam?-N4)](ZnCl₄)₂ and brown [Ni^#(H₂diam?-N4)(NCS)₂](NCS)₂·3H₂O (µ_ef = 3.14 B.M. at 25°C) crystallised from solutions in propan-2-ol of the residual gum from the reduction of ‘[Ni(dino)]Cl₂’ when HClO₄, ZnCl₂ or NaNCS were added. Recrystallisation of the thiocyanato compound from aqueous ammonia gave lustrous brown crystals of [Ni^#(diam?-N4)(NCS)₂]·0.5H₂O.^[11]

Reaction of equimolar diam and Na₃[Co(CO₃)₃] in solution rapidly forms yellow [Co(diam-III-N6)]³⁺ salts:^[56] [Co(diam-III-N6)]Cl₂·ClO₄, FEBZOB,^[27] FEBZOB10,^[24] [Co(diam-III-N6)](ClO₄)₃, NOZHAL,^[25] [Co(diam-III-N6)]Cl₃·2H₂O, RUPFOX,^[26] [Co(diam-III-N6)]Cl₃·3H₂O, [Co(diam-III-N6)]Cl₂·ClO₄ and [Co(diam-III-N6)]Br₂·ClO₄. The mixed anion salts are much less soluble than the single anion salts.^[56] Evaporation of a solution formed by reaction of [H₆(diam)]Cl₆ with Na₃[Co(CO₃)₃]·3H₂O, without acidification, gave yellow crystals of composition [Co(diam-III-N6)]₈·(CO₃)₅·Cl₁₄·56H₂O, which also crystallised from an equimolar aqueous solution of [Co(diam-III-N6)]Cl₃·3H₂O and Na₂CO₃.^[56]

When equimolar diam and [Co(OH₂)₆]Cl₂ in dilute HCl solution^[24] (or a solution of [Co(diam-III-N₆)]³⁺ reduced with Zn,Hg/HCl^[56]) was exposed to the air, green trans-[Co(H₂diam-III-N4)]Cl₂]³⁺, red trans-[Co(Hdiam-III-N5)]Cl]³⁺ and yellow [Co(diam-III-N₆)]³⁺ formed, in proportions dependent on the acidity. The highest proportion of trans-[Co(Hdiam-III-N5)]Cl]³⁺ was formed at ~1 mol dm⁻³ HCl, with increasing amounts of the N6 cation formed as the HCl concentration decreased.^[56] The trans-[Co(H₂diam-III-N4)]Cl₂]³⁺ and trans-[Co(Hdiam-III-N5)]Cl]³⁺ ions were separated by chromatography^[24] or by crystallisation.^[56] On evaporation of the solution, trans-[Co(H₂diam-III-N4)]Cl₂]Cl₃·3H₂O crystallised. On addition of perchlorate, trans-[Co(H₂diam-III-N4)]Cl₂](ClO₄)₃·3H₂O, or on addition of ZnCl₂ and ethanol, trans-[Co(H₂diam-III-N4)Cl₂)]ZnCl₄·Cl·0.5H₂O·C₂H₅OH, KUWBIO).^[28] crystallised. Evaporation of the red filtrate, after crystallisation of green trans-[Co(H₂diam-III-N4)]Cl₂]Cl₃·3H₂O, gave red crystals of trans-[Co(Hdiam-III-N5)Cl]Cl₃·3H₂O (or, on addition of ZnCl₂ and propan-2-ol, of trans-[Co(Hdiam-III-N5)Cl)]ZnCl₄·Cl·0.5H₂O·0.5C₃H₇OH, KUWBEK).^[28] Substituting HBr for the HCl formed trans-[Co(H₂diam-III-N₄)Br₂]Br₃·H₂O.^[56]

When a solution of trans-[Co(H₂diam-III-N4)Cl₂]³⁺ in dilute HClO₄ was heated, trans-[Co(H₂diam-III-N4)(OH₂)Cl)]⁴⁺ and trans-[Co(H₂diam-III-N4)(OH₂)₂)]⁵⁺ slowly formed sequentially. When a solution of trans-[Co(H₂diam-III-N4)Cl₂]³⁺ in dilute HClO₄ slowly evaporated, trans-[Co(diam-III-N4)(OH₂)₂)](ClO₄)₃·H₂O crystallised.^[56]

Heating trans-[Co(H₂diam-III-N4)Cl₂]Cl₃ in water with NaNCS or Na(MeCO₂) forms violet-brown trans-[Co(H₂diam-III-N4)(NCS)₂](NCS)₃·2.5H₂O or purple trans-[Co(H₂diam-III-N4)(OCOMe)₂]Cl₃·5H₂O, respectively.^[56] Reaction with CN⁻ forms yellow trans-[Co(diam-III-N4)(CN₂)]ClO₄·2H₂O^[25] (better prepared by reaction of trans-[Co(diam-I-N5)(OH)]²⁺ (below) with CN^−[91]). Preparations of trans-[Co(diam-III-N4)(CN)₂]·trans-[Co(H₂diam-III-N4)(CN)₂](ClO₄)₄·4H₂O, FOMCIU and Na·trans-[Co(diam-III-N5)CN)](ClO₄)₃, FOMCEQ have been reported.^[29]

Dark brown peroxo compounds form when an equimolar solution of a Co²⁺ salt and diam in water or methanol is exposed to the air at ambient temperatures. When [Co(OH₂)₆](ClO₄)₂ was used, trans-[{Co(diam-I-N5)}₂(µO₂)](ClO₄)₄·H₂O, KUWZEH,^[28] crystallised. Reaction of diam with excess [Co(OH₂)₆]Cl₂ (or -Br₂) in air gave red-brown crystals formulated as trans-[{Co(diam-I-N5)]₂(µO₂)]CoCl₄·2Cl·10H₂O (or –CoBr₄·2Br·8H₂O), respectively.^[56]

In basic aqueous solution trans-[{Co(diam-I-N5)}₂(µO₂)](ClO₄)₄ slowly forms [Co(diam-III-N6)]³⁺.

When an aqueous solution of trans-[{Co(diam-I-N5)}₂(µO₂)](ClO₄)₄ was heated, the colour changed to orange and orange trans-[Co(diam-I-N5)(OH)]ClO₄)₂·H₂O crystallised. This compound was also formed by a rapid reaction of [Co(diam-III-N6)](ClO₄)₃ in 2 mol dm⁻³ NaOH solution. Reaction of trans-[Co(diam-I-N5)(OH)](ClO₄)₂·H₂O with cold aqueous HCl formed orange coloured trans-[Co(Hdiam-I-N₅)(OH₂)]Cl₃·ClO₄, KUWZUX,^[28] and with ZnCl₂ formed red [Co(Hdiam-I-N5)Cl]ZnCl₄·H₂O, KUWZOR^[28] while heating with conc. HCl formed red trans-[Co(Hdiam-II-N5)lCl₃·3H₂O, KUXBAG^[28] (Fig. 8), with the uncommon cyclam configuration II. The configuration observed would be formed by inversion of one NH centre of diam-Iab, inversion of the second NH centre would form diam-IIIaa. It is probable that this is a metastable transient between configurations I and III, trapped by the strongly acidic solution.

Fig. 7.  The cation of trans-[Cu(cis-diam-Iab-N5)(OClO₃)]ClO₄, ROMWOF. One amine substituent and one perchlorate oxygen (shown) are weakly trans-coordinated (Cu–N = 2.323(4), Cu–O = 2.732(4) Å).

Fig. 8.  The cation of trans-[Co(Hdiam-II-N5)Cl] Cl₃·3H₂O, KUXBAG.^[28]

The pH of an aqueous solution of cis-diam was adjusted to 7, [Co(OH₂)₆]Cl₂ and charcoal were added and the solution aerated. The cis-[Co(cis-diam-V-N6)](ClO₄)₃·2H₂O product, RUPFOX^[26] was isolated by chromatography in ~30% yield.

Heating CrCl₃ with diam in DMSO formed [Cr(diam-III-N6]Cl₃·3H₂O, which recrystallised from hot dilute HCl as trans-[Cr(Hdiam-III-N5)(OH₂)]Cl₄·3H₂O. The amine substituent re-coordinated in basic solution.^[11,30]

Chromatography of the solution formed by reaction of CrCl₃ with [H₆diam]Cl₆/6NEt₃ in anhydrous, de-oxygenated EtOH, using Sephadex-SP-C25 and eluting with NaClO₄ solution, gave two close-running bands. The first yielded trans-[Cr(diam-III-N5)(OH)](ClO₄)₂·1.5H₂O and the second cis-[Cr(diam-III-N5)(OH)](ClO₄)₂, with the configurations assigned after extensive analysis of the electronic and ESR spectra.^[30] A third, slower running band yielded [Cr(diam-III-N6](ClO₄)₃, JEVCAO.^[30]

Similar preparations using [H₆cis-diam]Cl₆ formed products isolated as cis-[Cr(cis-diam-V-N6)](ClO₄)₃·2H₂O, HAHLOR and cis-[Cr(cis-diam-V-N6](ZnCl₄)_1.5·3H₂O.^[16]

[H₆diam]Cl₆ was reacted with [Fe(OH₂)₆]SO₄·H₂O for 1 day in de-oxygenated water at ambient temperature. Low-spin [Fe(diam-III-N₆](ClO₄)₃, SANLAU^[31] and [Fe(diam-III-N₆](ClO₄)₂·Cl, SIZCEJ.^[32] were isolated by chromatography.

Reaction of diam with [Fe(OH₂)₆]SO₄·H₂O in water under rigorously anaerobic conditions enabled isolation of blue, low-spin [Fe(diam-III-N6](PF₆)₂, PAZXAP.^[33]

Reaction of [V(acac)₃] with [H₆diam]Cl₆/6Et₃N in MeOH for 2 days formed a dark yellow solution. A purple coloured band was isolated by chromatography. When evaporated this changed to green and green crystals of trans-[VO(diam-I-N5)](ClO₄)₂, TAFPIZ^[34] (Fig. 9) were isolated.

Fig. 9.  The cation of trans-[VO(diam-I-N5)](ClO₄)₂.

Attempts to isolate salts of [Cd(diam-III-N₆)]²⁺ from solutions containing diam and Cd²⁺ were unsuccessful.^[15] When a solution of equimolar diam and CdCl₂ in water was heated, fine white crystals of composition Cd·(diam)·Cl₂·2H₂O formed as the solution cooled.^[11]

The compound cis-[Cd(cis-diam-V-N6)](ClO₄)₂, VOPLER,^[15] was prepared as for the Zn^II analogue.

Compounds of Pd^II and Pt^II with diam were prepared by heating [PdCl₄]²⁻ or [PtCl₄]²⁻ salts with diam (or [H₆diam]Cl₆/6NEt₃) in water. Isomeric Pd^II products were isolated as perchlorate salts by chromatography as [Pd(diam-IIIaa-N4)](ClO₄)₂·6H₂O, TACVOI^[37] and [Pd(diam-IIIbb-N4)](ClO₄)₂, NESXIU.^[36] Compounds with the amine substituents protonated crystallised from acid solution; [Pt(H₂diam-IIIbb-N4)](ClO₄)₄·6H₂O, TACVUO.^[37] NESXIU and TACVUO have the uncommon diam-IIIbb-N4 configuration.

Oxidation of the Pt^II compound with Cl₂ formed trans-[Pt(H₂diam-IIIaa-N4)Cl₂](ClO₄)₂·Cl₂·4H₂O, VOZZAL and trans-[Pt(H₂diam(NCl₂)-IIIaa-N4)Cl₂](ClO₄)₂ (diam(NCl₂) = 6,13-dimethyl-cyclam-6,13-dichloro-amine), VOZYUE.^[38]

Reaction of H₂[PdCl₄] with diam initially formed [Pd(H₂diam-III-N4)]Cl₃·0.5[PdCl₄], which recrystallised from hot dilute HClO₄ as [Pd(H₂diam-III-N4)](ClO₄)₄·6H₂O, or from aqueous NH₃ as [Pd(diam-III-N4)](ClO₄)₂·0.5H₂O.^[11]

Equimolar RhCl₃ and diam were refluxed in water or methanol for ~10 h and two compounds isolated from the resulting solution by chromatography; yellow trans-[Rh(H₂diam-III-N4)]Cl₂](ClO₄)₂·2H₂O and pale yellow trans-[Rh(Hdiam-III-N5)Cl](ClO₄)₃·3H₂O. Heating the latter in NaOH solution and then evaporating with added ClO_4⁻ gave colourless crystals of [Rh(diam-III-N6)](ClO₄)₃, SERHUS.^[35]

When RhCl₃ and diam were refluxed in water or methanol for 10 h, and then NaClO₄ and ZnCl₂ added, [Rh(diam-III-N6)]₃(ClO₄}₅·(ZnCl₄)₂·3H₂O crystallised.^[11,35]

Reaction of diam with molybdenum carbonyl formed [diam(Mo(CO₄)₂)]·DMF, RUJBED with two Mo(CO)₄ groups each bonded to the diam by one amine substituent and an adjacent cyclam nitrogen in a bidentate and exo-cyclic manner^[39] (see Table 2 for the related monam compound RUJBAZ).

Table 2.  Compounds of tetraaza cyclam-mono-amines with structures in the CCDC database.

An aqueous solution of lead acetate was added dropwise to a solution of diam, with the pH adjusted to below seven with acetic acid (in final equimolar proportions). An aqueous solution of NaClO₄ was then added dropwise until the solution became turbid. White crystals of composition Pb²⁺·(diamH⁺)₃·(CH₃CO₂⁻)₃·(ClO₄⁻)₂·(H₂O)_3.5 slowly formed. A similar preparation using lead nitrate formed crystals of composition Pb²⁺·(H₃diam³⁺)₅·(NO₃⁻)₇·H₂O.^[11]

When the pH of an equimolar aqueous solution of [H₆cis-diam]Cl₆ and Pb(NO₃)₂, plus NaClO₄, was raised to 6 with NaOH and the solution evaporated, colourless crystals of cis-[Pb(cis-diam-V-N6)(OH₂)](ClO₄)₂, WENVAM^[40] formed over a period of weeks.

When HgCl₂ and NaClO₄ were added to an aqueous solution of [H₆diam]Cl₆ and the pH raised to 6 with NaOH, colourless crystals of [(H₂diam)(HgCl₃)₂]·[diam(HgCl₂)₂)]·2H₂O, WENVIU^[40] (Fig. 10) slowly crystallised. The diam is in exo-cyclic coordination to chloro-Hg²⁺ ions; in molecule 1 only by an amine substituent, in molecule 2 by an amine substituent and one ring N-atom.

Fig. 10.  The molecules 1 (upper) and 2 (lower) of WENVUI.

Preparative methods for metal-ion compounds of diam and cis-diam are generally like those used for cyclam. Preparations for diam under basic conditions usually yield trans-[M(diam-IIIaa-N6]ⁿ⁺ products. All reported structures of diam compounds have the cyclam nitrogen atoms in planar coordination, but with folded, cis, coordination inferred from the d–d spectrum for one Cr^III compound. Most metal ions react with diam to form products with the aa substituent configuration. Products with the bb configuration are formed by Cu^II, Pd^II and Pt^II. A Co^III compound with the uncommon cyclam configuration II was also prepared. Metastable configuration diam-I-N5 compounds are formed by reaction of Cu²⁺ with diam, hydrogenation of [Ni(trans-dino)]²⁺, by exposure of [Co(diam)]²⁺ to oxygen and by reaction of [Co(diam-III-N₆)]³⁺ in 2 mol dm⁻³ NaOH solution. It is possible that compounds of these isomers are also formed by other elements, but not yet isolated.

All reported structures of compounds of cis-diam, other than with Cu^II, have folded macrocycle, cis-[M(cis-diam-V-N6)] configurations. Two compounds of Cu^II (and possibly compounds with Ni^II) have planar-macrocycle structures.

The cyclam ring secondary amine groups of coordinated diam are non-labile because of their inclusion in the ring-structure. The primary amine substituents of diam-III-N6 ions are more labile and can usually be protonated or substituted, rapidly for normally labile ions such as Ni^II, Cu^II or Zn^II, slowly for normally non-labile ions, such as Co^III. [Ni(diam-III)]²⁺ and [Cu(diam-III)]²⁺ are extremely resistant to acid de-metalation, while [Zn(diam-III)]²⁺ and [Ni(diam-I)]²⁺ slowly hydrolyse in acid.

Most reported cis-diam compounds were prepared under basic conditions and have [M(cis-(cis-diam-Vaa-N6)] configurations. Reaction of Cu²⁺ with cis-diam forms trans-[Cu(cis-diam-I-N5)(OClO₃]⁺ and trans-[cis-H₂diam-IIIaa-N4)(OClO₃)₂]²⁺. It is likely that other cis-diam compounds with the amine substituents protonated, or displaced by other ligands, could be prepared, analogous to these and the putative [Ni(cis-diam)]²⁺ compounds mentioned in Compounds of Nickel(ii) with cis-diam.

Early in the studies of these ligands, structures of compounds of [Co(diam-III-N6)]³⁺, [Cr(diam-III-N6)]³⁺, [Ni(diam-III-N6)]²⁺ and [Cu(H₂diam-III-N4)]⁴⁺ cations were determined by X-ray crystallography. The Co^III compound, in particular, raised interest because the Co–N bond lengths were shorter than those of other Co^III–N₆ compounds such as [Co(seph)]³⁺ or [Co(en)₃]³⁺. The d–d spectra, reduction potentials and Co^III/Co^II self-exchange rates were also indicative of a higher ligand field strength for the [Co(diam-III-N6)]³⁺ cation. This led to speculation that for [diam-III-N6)]³⁺ the ligand might somehow be ‘constraining’ the Co^III ion.^[27] For [Co(diam-III-N₆)]³⁺ the Co–N distances to the cyclam nitrogen and amine substituent atoms are both unusually short. For the larger Ni^II and Zn^II ions the Ni–N distances are more similar to those of other N₆ type ligand compounds and the substituent Ni–N distances are longer than the cyclam Ni–N distances.

For any MN₆ species the M–N distances will be determined by the intersection of two energy–distance relationship curves; firstly the bond energy of the MN₆ group, determined by electronic interactions between the Mⁿ⁺ ion and N donor-atoms and secondly the strain energy within the ligand(s) arising from positioning the N-atoms in their coordination sites, which will increase as the centre–N distances decreases. The short Co–N distances for [Co(diam-III-N6)]³⁺ suggest that the intra-ligand repulsive interactions are smaller for diam than other N₆ ligands, probably because of fewer H–H repulsive interactions.

Strain energies versus centre–N distance were calculated for the diam molecule in the III-N6 configuration, with the N atoms constrained to lie on a sphere.^[81] Three conformations for the [M(diam)]ⁿ⁺ ion were identified, differing principally by the relative conformations of the two five-membered chelate rings, conformations, 1 and 3 with centrosymmetrical δ,λ and chiral, 2 with δ,δ, λ,λ arrangements (also describable in terms of the relative axial or equatorial orientations of the C3, C4 and C9, C10-ring atoms.^[48] These had strain energy versus distance relationships with minima at ~1.93, 2.00 and 2.1 Å, respectively. Observed structures for [Co(diam-III-N6)]³⁺ compounds (Co–N ~1.94 Å), and other small M³⁺ ions, have centrosymmetrical cations with the conformation 1, while structures for [Ni(diam-III-N6)]²⁺ (Ni–N ~2.07 Å for cyclam N-atoms, with longer Ni–N for the amine substituents, and also for other larger M²⁺ ions), are chiral, with the conformation 2. These conformational variations have been confirmed by NMR^[16] and later molecular mechanics studies.^[48,81,82]

Calculated strain energies increase steeply with increasing metal-ion size and [Zn(diam-III-N6)](ClO₄)₂ has the largest reported M–N distances of ~2.1 Å, attempts to prepare endo-cyclic compounds of Cd²⁺, Hg²⁺ or Pb²⁺ were unsuccessful.

Similar calculations for cis-[M(cis-diam-V-N6)]ⁿ⁺ suggest that the ligand strain energy minimum occurs at a larger M–N distance and increases less steeply with increasing M–N distance for cis-diam than for diam, and so the cis-isomer would be more compatible with larger metal ions.^[16,81] cis-[Cd(cis-diam-V-N6)](ClO₄)₂, VOPLER, with Cd–N ~2.4 Å^[16] and cis-[Pb(cis-diam-V-N6)(OH₂](ClO₄)₂, WENVAM, with Pb–N ~2.8 Å have been prepared.^[40] Variations of the structures and spectroscopic parameters of the cis-[M(cis-diam-V-N6)]ⁿ⁺ cations, M = Co^III, Cr^III and Ni^II have been evaluated.^[16]

Reaction of [Cu(en)₂](NO₃)₂ with nitropropane, formaldehyde and NEt₃ forms brown [Cu(Etdino)](NO₃)₂ (Etdino = 6,13-diethyl-6,13-dinitro-cyclam), which recrystallised from aqueous HClO₄ as purple [Cu(Et₂dino)](ClO₄)₂.^[41] Similar reaction of [Ni(en)₂]Cl₂ produces [Ni(Etdino)]Cl₂.^[12]

The [Cu(Etdino)]²⁺ cation(s) were reduced with Zn/HCl and isomeric [Cu(Etdiam)]²⁺ (Etdiam = 6,13-diethyl-cyclam-6,13-diamine) ions, formed by reaction with Cu²⁺, were separated by chromatography into five bands with distinctive d–d spectra. These were each reduced with Zn/HCl, and the ligands characterised by NMR spectroscopy. Bands 1, 2, 3 and 5 contained the [Cu(trans-Etdiam)]²⁺ isomer and band 4 the [Cu(cis-Etdiam)]²⁺ isomer (cf. the reduction of [Cu(trans-dino)]²⁺. Compounds of Zinc(ii) with diam and cis-diam). [H₄(trans-Etdiam)](ClO₄)₂·2H₂O, ZUSCEN,^[41] reacted with Na₃[Co(CO₃)₃] to form trans-[Co(trans-Etdiam-IIIaa-N6)](ClO₄)₃·H₂O, ZUSCIZ.^[41]

Reactions under the same conditions of [Cu(en)₂]²⁺, [Cu(rac-pn)₂]²⁺ or [Cu(2-methyl-pn)₂]²⁺ with formaldehyde and nitroethane, form acyclic mono-nitro and macrocyclic dinitro products in 2:3, 10:1 and ~50:1 proportions, respectively. The acyclic products from rac-pn, REVQIS, and 2-methyl-pn, REVQOY,^[42] have the diamine residue methyl substituents remote from the –CH₂–C(Me, NO₂)–CH₂– link. The macrocyclic compound formed from pn was reduced with Zn/HCl and the hexa-hydrochloride salt of the cyclic amine product isolated and reacted with Cu²⁺ and base. The major product, isolated by chromatography, was trans-[Cu(2,9-meso-6,13-diamminium-2,6,9,13-tetramethyl-cyclam-IIIaa-N4)(OClO₃)₂](ClO₄)₂, NOPKUY,^[83] with the C2 and C9-methyl substituents equatorially oriented.

Reaction of [Ni(rac-pn)₂]Cl₂ with nitroethane and formaldehyde forms [Ni(2,9-meso-2,6,9,13-tetramethyl-6,13-dinitro-cyclam)ICl₂.^[12]

Reactions of metal-ion diamine compounds with nitromethane and aldehydes generally produce extensive tars. Reaction of [Cu(en)₂]²⁺ with four mole proportions of acetaldehyde, followed by reaction with nitromethane, forms [Cu(5,7,12,14-tetramethyl-6,13-dinitro-cyclam)]²⁺, which was reduced by Zn/HCl to form 5S,7S,12R,14R-5,7,12,14-tetramethyl-cyclam-6,13-diamine, L.^[26,83] The compounds [H₄L](ClO₄)₄·2H₂O, NOCSUT, [Cu(H₂L-IIIaa-N4)](ClO₄)₄·2H₂O, NOCTAA.^[83] NOCSUT and NOCTAA are isomorphous. trans-[Cu(H₂L-IIIaa-N4)(ONO₂)₂]-(NO₃)₂·4H₂O, QUXVAH^[51] and trans-[Co(L-IIIaa-N6)]Cl₂·ClO₄, RUPFIR^[26] have been structurally characterised (see Scheme 6).

Scheme 6.  Preparations of compounds of 5S,7S,12R,14R-5,7,12,14-tetramethyl-cyclam-6,13-diamine.

Protonation constants, pK_as, for 5S,7S,12R,14R-5,7,12,14-tetramethyl-cyclam-6,13-diamine, at 298 K in 0.1 mol dm⁻³ Et₄NClO₄, are: 11.1(1), 10.3(1), 5.5(1), 5.2(1) 3.5(1). Molecular mechanics modelling of strain energies of the Co^II and Co^III cations and their relationship to redox couples and self-exchange rates are discussed.

Mild reduction of the 6,13-dinitro(Cu) ion formed the 6,13-diketo oxime compound (L), isolated as [Cu(L-III-N4)Cl]Cl·7H₂O, NOCTEE^[83] and [Cu(L-III-N4)Cl]BF₄·H₂O, TASCOF,^[84] which have the uncommon cyclam configuration II.

Reaction of [M(propane-1,3-diamine)₂]²⁺ with formaldehyde and nitroethane forms [M(3,15-dinitro-3,15-dimethyl-[16]ane)]²⁺, M = Cu²⁺ or Pd²⁺, with yields higher for Pd²⁺. Reduction by Zn/HCl forms the 3,15-cis-diamine. The overall yield of the amine was ~13% via the Cu^II compound and ~40% via the Pd^II compound. cis-[Cu(cis-[16]-diam-V-N6)](ClO₄)₂, CAHYEQ,^[85] has a tetragonal structure, with significantly longer Cu–N bonds to one ring N-atom (2.35(4) Å) and one substituent N-atom (2.33(3) Å) which are in tetragonal positions.

Reaction of [Cu(trans-(R,S)-cyclohexane-1,2-diamine)₂]²⁺ or [Cu(cis-(R,R or S,S)-cyclohexane-1,2-diamine)₂]²⁺, as nitrate or perchlorate salts, with nitroethane, formaldehyde and base, form the (mono-nitro) acyclic and (di-nitro) macrocyclic condensation products, which were isolated by chromatography. The nitro groups of one acyclic Cu^II compound were reduced with Zn/HCl, and [Co(RR,RR-1,3-bis(2′-aminocyclohexylamino)-2-methylpropane-2-amine-N5)Cl]Cl·ClO₄·2H₂O, WAPPIM, was prepared from the isolated amine salt.^[86]

Cu^II and Ni^II compounds of linear tetraamines react with formaldehyde and nitroethane in basic solution to form tetraaza-macrocycle compounds with nitro and methyl substituents on the central carbon atom of one six-membered chelate ring. The Cu^II compounds have been reduced by Zn/HCl to form the methyl, amine substituted cyclic tetraamines, which have been isolated by ion exchange chromatography as the penta-hydrochloride salts, from which compounds of transition-metal ions have been prepared. The 3-methyl-3-nitro-1,5,9,13-tetraazacyclohexadecane (L16) compound was prepared in higher yield as the Pd^II compound (see Scheme 7). Compounds with reported structures are shown in Table 2.

Scheme 7.  Preparations of mono-methyl-mono-amine substituted tetraaza-cyclic tetraamines via nitroethane-formaldehyde condensations and Zn/HCl reductions.

Some related compounds are included, including cyclam-6-amine (L14¹), which was synthesised by ‘non-templated’ reactions^[58] (Scheme 8) and amine/methyl substituted cyclic tetraamines with other substituents, formed via reaction of variously substituted linear tetraamine Cu^II cations with EtNO₂ and formaldehyde (Scheme 9).

Scheme 8.  Preparations of cyclam-6-amine, L14¹, Ni^II compounds.

Scheme 9.  Preparations of mono-amine substituted tetraaza-cyclic tetraamines with additional substituents, formed via nitroethane-formaldehyde reactions.

Most reported structures have octahedral trans-N5(X) coordination of the ligand to a M³⁺ metal ion, usually with configuration IIIa, occasionally with configurations Ia, many with cyano-linked di-nuclear structures. Compounds of a pentaamine with different configurations were either prepared by different procedures or isolated from mixed products by chromatography.

Dimensions of trans-[Co(ligand-III-N5)Cl]²⁺ cations with 13–16 ring-membered ligands, included in Table 2, show little variation in Co–N and Co–Cl distances with ring size or substituents.

Formation constants for metal ions with mono-methyl substituted cyclic tetraamines with a range of ring sizes have been reported.^[87] Complexation kinetics for Cu^II and Ni^II with L15 have been reported.^[88] Comparative basic hydrolysis rates for chlorocobalt(iii) compounds of L13, L14¹, L15 and L16 have been measured.^[52]

Reaction of [Cu(3,6,9-triazaundecame-1,15-diamine)]²⁺ with nitroethane and formaldehyde forms [Cu(15-methyl-15-nitro-1,4,7,10,13-pentaazacyclohexadecane), which was reduced with Zn/HCl to form 15-methyl-1,4,7,10,13-pentaazacyclo-hexadecane-15-amine salts, which formed octahedral cations with Co^III, Cr^III and Fe^III. [Co(L16-N6)](ClO₄)₃, CAJBEV, has the amine substituent coordinated trans to the 7-aza group^[89] (see Scheme 10).

Scheme 10.  The synthesis of [Co(15-methyl-1,4,7,10,13-pentaazacyclohexadecane-15-amine)](ClO₄)₃.

Modifications of the amine substituents of diam, monam or homologues are shown in the following reaction schemes, which include CCDC refcodes of structures.

Reactions of [Cu(diam-III-N4)]²⁺ (and [Pd(diam-III-N4)]²⁺ with nitrous acid form exocyclic-6,13-bis(methylene)-cyclam compounds, with the structure of [Cu(L-III-N4)]²⁺)(ClO₄)₂, JUTXIF, reported^[45,90] (see Scheme 11).

Scheme 11.  Formation of 6,13-bis(methylene)-, 6,13-bis-(dimethylamine)- and 6,13-bis-(dichloromethyl-amine)-cyclam compounds.

Oxidation of trans-[Pt(H₂diam-IIIbb-N4)Cl₂]²⁺ with Cl₂ forms the 6,13-dimethy-cyclam-6,13-bis(dichloro-amine), L, compound trans-[Pt(L)-IIIbb-N4)Cl₂](ClO₄)₂, VOZYUE^[38] (see Scheme 11).

Reactions of trans-[Cu(diam-IIIaa-N4)(OClO₃)₂], [Ni(diam-IIIaa-N6)](ClO₄)₂ or trans-[Co(diam-IIIaa-N4)(CN)₂]ClO₄ with acetic or propionic anhydrides in DMF form 6,13-di-methyl-6,13-bis((m)ethyl-amido)-cyclam, L, compounds, [Cu(L-IIIbb-N4)(OClO₃)₂], DAPWOH^[46] and trans-[Co(L-IIIbb-N4)(CN)₂]ClO₄·2H₂O, BOHJOY.^[47] The Ni^II cation forms sgs square-planar, and also tgs octahedral compounds with a variety of trans ligands. The structure of trans-[Ni^#(L-IIIbb-N4)(OH₂)]·trans-[Ni^#(L-IIIbb-N4)(OH₂)(OCOOH)]ClO₄·HCO₃, NAJZUU, which crystallised from NaHCO₃ solution, was determined^[91] (see Scheme 12).

Scheme 12.  Formation of 6,13-dimethyl-cyclam-6,13-bis(ethyl-amide) compounds.

A vigorous reaction of [Ni(diam-III-N6)](ClO₄)₂ dissolved in dimethylformamide with oxalyl chloride formed sparingly soluble, lilac coloured, trans-dichloro-(6,13-dimethyl-cyclam-6,13-bis-(N,N-dimethyl-formamidinyl))nickel(II) perchlorate dihydrate, UZAJEL^[92] (see Scheme 13).

Scheme 13.  Formation of trans-dichloro-(6,13-dimethyl-cyclam-6,13-bis-(N,N-dimethylformamidinyl-IIIaa-N4))nickel(ii) perchlorate dihydrate, UZAJEL.

Refluxing a solution of [Cu(diam)]²⁺ in formic acid/formaldehyde (a standard method for methylating amines^[44,93]) for 2 days forms isomeric 6,13-bis(dimethylamino) Cu^II cations as the major products. Compounds with isomeric cations [Cu(L-IIIaa-N4)(OClO₃)₂], RAXKOQ and [Cu(L-IIIbb-N4)(OH₂)₂]Cl₂, RAXKIK were isolated by chromatography, (cf. Compounds of Coppe(ii) with diam and cis-diam). The isomerism was investigated by molecular modelling^[94] (see Scheme 11).

Reaction of [Cu(diam)]²⁺ with formaldehyde and reaction of [H₆diam)]⁶⁺ with pyridine-2-carbaldehyde form polycyclic products incorporating fused 1,3-diazetidene (diazacyclopentane) rings, which are tautomers of the methylene imines.

Refluxing an aqueous solution of [Cu(OH₂)₄](NO₃)₂, [H₆diam)]Cl₆ and formaldehyde for 24 h formed a mixture of polycyclic products incorporating fused 1,3-diazetidene rings, tautomeric with methylene imines, which were separated by chromatography and the structures of three determined^[95] (see Scheme 14).

Scheme 14.  Compounds formed by reaction of [Cu(diam)]²⁺ with formaldehyde, RAXKUW, RAXLAD and RAXLEH.

Reaction of [H₆diam]Cl₆·2H₂O with pyridine-2-carbaldehyde forms trans-6,14-dimethyl-8,16-bis(2-pyridyl-methyl)-1,4,7,9,12,15-hexa-azatricyclo(12.2.1.16,9)octadecane, BETZOQ, with 1,3-diazetidene rings^[96] (see Scheme 15).

Scheme 15.  A compound formed by reaction of [H₆diam]Cl₆·2H₂O with pyridine-2-carbaldehyde, BETZOQ.

Diam and monam react with aldehydes under anhydrous conditions to form imines (or 1,3-diazetidene tautomers), which are reduced by NaBH₃CN or NaBH₄ to form secondary amine substituents. Metal-ion compounds were prepared from the resultant amines. Alternatively, the metal ion (usually Cu^II) compound of diam or monam was reacted with the aldehyde and the resulting imine compound reduced, usually with NaBH₃CN.

Reactions of [Co(diam-III-N6)](MeCO₂)₃ with formaldehyde in MeOH under anhydrous conditions form the 6-mono- and 6,13-bis-(methyl-imine), NOZHEP, cations, which were reduced with NaBH₄ to form the 6-mono- and 6,13-bis-(methyl-amine), NOZHIT, cations, respectively^[97] (see Scheme 16).

Scheme 16.  Formation of 6- and 6,13-bis-(methyl-amine) substituted cyclam compounds of Co^III by reduction of imines formed with formaldehyde, NOZHEP, NOZHIT.

Reaction of monam with glyoxylic acid, reduction of the resulting imine with NaBH₃CN and reaction of the resulting N-carboxymethyl substituted macrocycle with Cu²⁺ forms isomeric cations, isolated as trans-[Cu(L-IIIa-N4)(OClO₃)₂]·3H₂O, LOWCAB and [{Cu(L-IIIb-N4}₂](ClO₄)₄·H₂O, LOWCEF^[98] (see Scheme 17).

Scheme 17.  Compounds formed via reactions of monam with glyoxylic acid, LOWCAB and LOWCEF.

Reaction of [H6(diam)]Cl₆ with 4-carboxy-benzaldehyde and NaBH₃CN form the 6-(4-carboxy-phenyl-methyl-amine compound, which reacted with Na₃[Co(CO₃)₃]3H₂O to form the Co(III) compounds XASJUX and XASJOR^[99] (see Scheme 18). The electrochemistry of XASJUX chemisorbed onto TiO₂ was investigated.

Scheme 18.  Co^III compounds formed via reactions of diam with 4-carboxy benzaldehyde, XASJOR and XASJUX.

Reactions of monam with 4-carboxy-benzaldehydes and Cu²⁺ form 1,3-diazetidene type imine tautomers, LIZSUI and LIZTAP^[100] which are reduced by NaBH₄ to form the (4-carboxy-phenyl)-methyl) monam compound, WOHYEX. Reaction of 6-(2-or 4)-hydroxy-benzaldehyde with [Cu(monam)]²⁺ and NaBH₄ form 6- (2- or 4)-hydroxy-phenyl)-methyl-monam) compounds, WOHYAT and WOHXUM^[101] (see Scheme 19).

Scheme 19.  Cu^II compounds formed via reactions of monam with 4-carboxy-, or 2- or 4-hydroxy-, benzaldehyde and NaBH₃CN, LIZSUI, LIZTAP, WOHXUM, WOHYAT WOHYEX.

Reactions of trans-[Co(diam-N4)(OH₂)₂]³⁺ with a 4-formyl-benzo-(cyclic ether) and NaBH₃CN form compounds with benzo-cyclic ethers N-appended to [Co(diam-III-N5)]³⁺. The cyclic ethers can host cations, MOGVEJ, MOGVIN, MOGVOT, MOGVUZ and MOGWAG^[102] (see Scheme 20).

Scheme 20.  Co^III compounds of diam with N-appended benzo-cyclic ethers, MOGVEJ, MOGVIN, MOGVOT, MOGVUZ and MOGWAG.

Reactions of diam, monam (and homologues with different ring sizes) with carboxy-methyl-aromatics, reduction of the resulting imine functions with NaBH₃CN and reaction with metal ions form compounds with N-(methyl-aromatic) substituents. Compounds with methyl-phenyl, -naphthyl, and -anthacenyl aromatic groups and with mixed aromatic groups were formed to give XODTIT, XODTOZ and XODTUP from diam, and ECXIX, EXEXOD and ECXUJ from monam.^[103] The Zn^II compounds were used for photochemical studies of energy transfer between aromatic substituents, LESCOB.^[104] Reaction with 4-dimethylamino-benzaldhyde forms the 6,13-bis-(4-dimethylamino-methyl-phenyl) compound, which reacts with 9-carboxymethyl-anthracene to substitute 6-anthraceneyl-methyl for one 4-dimethylamino-methyl-phenyl group, YEBZIP^[105] (see Scheme 21).

Scheme 21.  Compounds of diam and monam with N-(methyl-aromatic) substituents, ECIXIB, ECIXOD, ECIXIX, ECIXUJ, XODTIT, XODTOZ, XODTUF, LESCOB and YEBZIP.

Compounds with N-(methyl-ferrocenyl) substituents were formed by reaction of diam or monam with carboxymethyl-ferrocene or bis(carboxymethyl)-ferrocene, reduction of the resulting imine compounds with NaBH₄ and subsequent reaction with metal ions^[106–108] (see Scheme 22).

Scheme 22.  Compounds of diam and monam with N-(methyl-ferrocenyl) substituents, QIXREU, QIXRIY, EWEJAY, EWEQIG and EWEQEC.

Compounds with 6- or 6,13-bis-(3-methyl-thiophene) substituents, were formed by reaction of [H₂diam]²⁺ with 3-(carboxymethyl)-thiophene and NaBH₃CN. Co^III compounds were formed by reaction with Na₃[Co(CO₃)₃]·3H₂O^[109,110] (see Scheme 23).

Scheme 23.  Co^III compounds of diam with N-methyl-3-thiophene substituents, MUKYOH, MUKYON, MUKZEY, MUKZAU, XEVYAZ, XEVYED, XEVYIH and HULSOX.

Epoxide activated cellulose was soaked in dilute HCl to hydrolyse any remaining epoxide groups, washed and then reacted with NaIO₃ in water. Reaction ceased after a period of hours, when the oxidised cellulose was again washed. Diam dissolved in a KH₂PO₄/K₂HPO₄ buffer and NaBH₃CN were added, the coupling reaction taking ~4 h at ambient temperatures. The washed and dried cellulose-diam had 4.2% N content, corresponding to a loading of 0.5 mmol of diam g^–1 of cellulose-diam (Scheme 24).

Scheme 24.  Chemical binding of diam to cellulose.

At pH 3 the cellulose-diam rapidly absorbed Cu²⁺, Ni²⁺, Co²⁺ and Fe²⁺, with residual solution concentrations of <0.02 ppm, with maximum loadings of ~1.2 mmol g^–1 dry weight, significantly higher than the nominal diam loading. At pH 1 only Cu²⁺ was appreciably absorbed. No Cu²⁺ was leached from the Cu²⁺ loaded cellulose-diam at pH 1.^[111]

Facile reactions of bis(ethane-1,2-diamine)-copper(ii) and -nickel(ii) cations with nitroethane and formaldehyde form (6,13-dimethyl-6,13-dinitro-4,8,11-tetraazacyclotetradecane)-copper(ii) or nickel(ii) cations. Reduction of the nitro functions of the Cu^II compound with Zn/HCl forms salts of isomeric 6,13-dimethyl-4,8,11-tetraazacyclotetradecane-6,13-diamine, with the amine substituents trans (anti), here labelled as ‘diam’, or cis (syn), here labelled as cis-diam, which can be separated by chromatography. Hydrogenation of the Ni^II cation forms [Ni(diam)]²⁺ (and probably also some [Ni(cis-diam)]²⁺, though this requires verification). Compounds of the isomeric amines with a wide range of transition metal ions have been prepared. The trans isomer, diam, forms metal-ion compounds with the cyclam nitrogen atoms in square-planar coordination, with both, one or neither of the amine substituents also coordinated. Most compounds formed by the cis-diam isomer have the cyclam nitrogen atoms in folded coordination, with the amine substituents coordinated cis. For the more intensively studied compounds of diam with Ni^II and Co^III, compounds with one or both of the amine substituents displaced by other ligands, or uncoordinated, free or protonated have been prepared. Compounds of Co^III and Ni^II have been prepared with cyclam configuration I, usually with N5 coordination. It is probable that related compounds can be prepared with cis-diam, but that requires verification. Cu^II, Pd^II and Pt^II react with diam to form isomeric products, distinguished by orientation of substituents relative to the cyclam secondary amine configuration.

Reactions of (3,7-diazanonane-1,9-diamine)-copper(ii) cations (and various C-substituted (3,7-diazanonane-1,9-diamine)-copper(ii) cations) with nitroethane and formaldehyde form (6-methyl-6-nitro-1,4,8,11-tetraazacyclotetradecane)-copper(ii) or nickel(ii) cations. Reduction of the nitro function of the Cu^II cations with Zn/HCl lead to variously C-substituted 6-methyl-cyclam-6-amines, from which compounds, mainly with Co^III or Cr^III, with the cyclic amine penta-coordinated, have been prepared.

The amine substituents of diam have been modified by methylation and by conversion into amide functions. Reaction of diam and monam, or their metal-ion cations, with functionalised aldehydes form imines which can be reduced to form functionalised secondary amine substituents. Compounds with variously substituted methyl-benzene, methyl-anthacene (and poly-aromatic molecules), methyl-ferrocene, methyl-benzo-cyclic ethers (which can host other cations) and methyl-thiophene have been reported. Similar reactions, which could bind a cyclic tetraamine (or its metal-ion compounds) to significant biological molecules would appear to potentially have widespread applications.

This is a review article. The data included was obtained from the primary publications listed as references. Secondary sources were American Chemical Society Chemical Abstracts and the Cambridge Crystallographic Data Centre database.

The author declares that he has no known competing financial interests or personal relationships that could have, or appeared to have, influenced the content of this paper.

This work did not receive any external funding. The author does not have any links to commercial interests or funding agencies. The author is an Emeritus Professor at the Victoria University of Wellington, which provided office space and access to computer, internet and library services, but no financial support.