Graeme H. Searle

The isomers of the bis(1-thia-4,7-diazacyclononane)cobalt(III) ion: separation and characterization

Abstract The two geometric isomers cis and trans of the bis(1-thia-4,7-diazacyclononane)cobalt(III) ion have been separated and crystallized as the pure isomers by fractional crystallization, aided by cation- exchange chromatography on SP-Sephadex. The pure isomers are characterized by 13 C NMR and UV-Vis spectroscopy. The isomers undergo a base- catalyzed isomerization to an equilibrium mixture cis/trans ca. 4/1. This isomerization is unusually facile, and occurs at a significant rate at pH down to about 5 at room temperature, so that chromatographic separations require acidic conditions. Separation by IE-HPLC has been demonstrated as a valuable tool to separate (3+)-charged complexes on an analytical scale, and can indicate the optimum conditions for preparative scale separations on SP- Sephadex columns. The isomerization process has been investigated as a function of temperature and pH using IE-HPLC, and 13 C NMR and visible spectroscopy.

Isomers of the bis(1,4,7-triazacyclodecane)cobalt(III) and (1,4,7,11,14,17−, hexaazacycloeicosane)cobalt(III) ions: Preparations, characterizations and isomerization

Abstract Cobalt(III) complex formation, using tacd·3HBr from the Richman-Atkins synthesis for cyclic polyamines, gives the trans and cis isomers of [Co(tacd) 2 ] 3+ in the equilibrium ratio 96:4 (perchlorates, 80°). Two other complexes are also formed, and these have been characterized ( 13 C and 1 H n.m.r. and visible spectroscopy) as single isomers mer, cis -[Co(hace)] 3+ and cis -[Co(dtah)] 3+ (dtah = 1,16-diamino-3,7,10,13-tetraazahexadecane). These hexamine ligands hace and dtah are therefore co-products with tacd in the Richman-Atkins synthesis, and they coordinate stereospecifically. The cis ⇄ trans [Co-(tacd) 2 ] 3+ isomerization is catalyzed by base or charcoal, and the mechanism proposed is intramolecular bond-rupture of a Cosec-NH bond and subsequent rearrangement of a trigonal-bipyramidal intermediate. This isomerization proceeds in Na 3 -PO 4 solution to give 100% trans , and use of this enables pure [Co(hace)] 3+ to be obtained by chromatographic separation from the preparative mixture. The ion-exchange chromatographic elution order of the four complexes is rationalized in terms of differential ion-associations.

Cobalt(III) complexes with N-methylethane-1,2-diamine (meen): synthesis and characterization of the isomers of [Co(meen)3]3+, (˚Co(meen)2(en)]3+ and [Co(meen)(en)2]3+

Abstract Of the twelve possible geometric isomers-dia-stereoisomers of [Co(meen) 3 ] 3+ . (meen= N -methyl-ethane-1,2-diamine), three isomers designated A , B and C according to their chromatographic elution order, have been detected from preparative mixtures. The highest yield and cleanest synthesis is CoCl 2 +3meen+dimethylsulfoxide, which gives pure red A -[Co(meen) 3 ]Cl 3 as the crystallized product, and recrystallization of this from water or methanol gives pure orange-red C . Each isomer is robust in acid, but equilibrates in water to the mixture A:B:C =3:1:2. These are therefore three NH diastereoisomers of the same geometry with respect to the NCH3 groups, which is mer by 13 C NMR spectroscopy. This mixture can be separated by cation-exchange chromatography on SP-Sephadex by using acidic Na 2 SO 4 . A second synthesis method was aerial oxidation of Co(Il)+3meen+H + in aqueous solution with charcoal at 80 °C. The charcoal and oxygen caused some demethylation of coordinated Co-meen, and the crude yellow-orange isolated product was a mixture of isomers of [Co- (meen) 3 ] 3 . (mostly C ), [Co(meen) 2 (en)] 3+ (three orange isomers F, G, H , of ten possible), [Co(meen)- (en) 2 ] 3+ (one orange-yellow diastereoisomer E of two possible) and [Co(en) 3 ] 3+ ( D ). The en complex species were separated on Sephadex using Na 3 PO 4 as eluent, and the designations D to H are in the elution order. Thus F , G and H are single diastereoisomers of the three different possible geometries (by 13 C NMR), and their ratios isolated ca . 5:1:36 should be approximately the equilibrium proportions.

A molecular mechanics analysis of [Co (medien) n (dien)2-n]3+ {n0-2} (dien diethylenetriamine or 1,5-diamino-3-azapentane; medien 3 - methyl-1,5- diamino-3 azapentane), and X-ray structural studies of the mer- and s-fac- [Co (medien) (dien)]3+ cations

Abstract Crystals of mer -[Co(medien) (dien)]Br 2 (ClO 4 )·H 2 O ( 1 crystallize in the monoclinic space group P2 1 /n with unit cell dimensions a =12.206(2), b =12.744(1), c =12.712(2) A, β=94.99(1)°, V =1969.9 A 3 , Z =4; crystals of s-fac - [Co (medien) (dien) ] (S 2 O 6 ) 1.5 ·0.5H 2 O ( 2 ) are monoclinic, space group P 2 1 with a =9.772(3), b =10.512(2), c =19.263(4) A, β=92.24(2)°, V =2014.2 A 3 , Z =4. The structures were refined by a full-matrix least-squares procedures in each case. At convergence, final R 0.065, R w 0.067 for 2578 reflections with I ⩾2.5σ ( I for ( 1 ) and R 0.061, R w 0.061 for 2845 reflections for ( 2 ). A molecular mechanics study of the isomers of the bis (tridentate)cobalt(III) complexes [Co(medien) n (dien) 2-n ] 3+ , n =0−2, (diendiethylenetriamine or 1,5-diamino-3-azapentane; medien3 methyl-1,5-diamino-3-azapentane) is reported. For the [Co(dien) 2 ] 3+ isomers, and the mer and s-fac isomers of [Co(medien)(dien)] 3+ , the structural details are satisfactorily modelled by MM2. For both the [Co(dien) 2 ] 3+ and [Co(medien)(dien)] 3+ systems, the MM2 procedure sbustantially overestimates the stability of the mer geometric isomers relative to the fac forms, although the relative stabilities of the s-fac/ u-fac forms correspond well with the observed isomer ratios. The calculated isomers ratios for the [Co(medien) 2 ] 3+ system agree with those found experimentally. The apparent variance in the capability of the MM2 procedure to predict the relative stabilities of the isomers in the three analogous systems is discussed.

Cobalt(III) complexes with N-methylethane-1,2-diamine (meen). Crystal structures of the stable isomers of [Co(meen)3]3+ and [Co(meen)2(en)]3+

Abstract The X-ray crystal structures of two geometric isomers-diastereoisomers of [Co(meen)3]3+, designated A and C, and one isomer of [Co(meen)2(en)]3+, designated F, are reported (meen=N-methylethane-1,2-diamine). A, C and F (as racemates) were isolated as their bromide salts and crystallized as dimono-, and mono-hydrates respectively. A crystallizes in the triclinic space group P 1 with unit cell dimensions a=8.231(2), b=8.682(1) and c=14.247(2) A, α=96.84(1), β=97.16(2) and γ=99.62(2)°, and Z=2. C crystallizes in the orthorhombic space group Pna21 (implying spontaneous resolution) with a=12.758(3), b=11.236(1) and c=13.19(1) A, and Z=4. Complex F is monoclinic, I2/a, with a=12.626(5), b=22.977(5) and c=12.619(6) A, β=97.84(4)°, and Z=8. The structures were solved by direct methods and each was refined by a full-matrix least-squares procedure. Final refinement details for A (those for C and F follow in parentheses): R 0.044 (0.040; 0.038), Rw 0.046 (0.041; 0.041) for 2487 (1318; 1693) reflections with I⩾2.5σ(I). The complex cations feature octahedrally coordinated Co(III) centres, and they are involved in complicated hydrogen bonding networks with the bromide anions and water molecules in the crystal lattices. The stereochemistries of the complex cations are (one enantiomer specified only) A: Λ-mer-[Co(meen)3]3+-RRR*-λδδ*; C: Λ-mer-[Co(meen)3]3+-RSR*-δλδ*; F: Λ-trans-CH3, cis-NH2-[Co(meen)2(en)] 3+-RR-δδδ. Equatorial methyl dispositions and lel ring geometries predominate, although A has one ring which is ob and which also has the methyl axial, and C has one ob ring.

The Crystal and Molecular Structure of the Unstable Facial Isomer of 1,4,7,10,13,16-Hexaazacyclooctadecanecobalt(III) Nitrate Monohydrate, fac-[Co(hexacyclen)](No3)3·H2O

Abstract The crystal structure of all-facial-[Co(hexacyclen)](NO3)3·H2 (the geometric isomer which elutes first on cation exchange chromatography) is reported. In the centrosymmetric cation the cobalt(III) atom exists in a slightly distorted octahedron, and the cation has approximate C 3 symmetry. The Co-N distances average 1.997(3) A and the average chelate angle is 83.6(1)°. In the crystal lattice the complex cations are linked by water molecules of crystallization thereby forming infinite chains and the nitrate groups are associated to both the cation and the water molecule. The compound crystallizes in the monoclinic space group C2/c with unit cell dimensions a = 13.980(4), b = 9.892(2), c = 16.002(6) A, β = 111.34(4)° and Z = 4. The structure was refined by a full-matrix least-squares procedure to final R = 0.037 for 1183 reflections with I ≥ 2.5 σ(I).

Stereochemistry in the macrocyclic (1,4,7,11,14,17-hexaazacycloeicosane)cobalt(III) ion and force field calculations

Abstract For the title complex [Co(hace)] 3+ three geometric isomers are possible, two of which can have NH diastereoisomeric forms, giving a total of six geometrically distinct species. All these are sterically quite crowded and reasonable conformational possibilities are limited. The most reasonable conformation for each diastereoisomer was selected for energy minimization. The experimental evidence (particularly 13 C NMR) indicates that the isolated complex is one diastereoisomer only, with C 2 symmetry, and from the energy calculations this is assigned as the lowest energy diastereoisomer Λ-mer, cis -RR/Δ-mer, cis -SS racemate. The next most stable form Λ-mer, cis -RS (C 1 symmetry) is 14 kJ mol −1 higher in energy which would account for the stereospecific coordination. The other four diastereoisomers are considerably higher in energy.

SULFUR-BONDED AND CARBON-BONDED FORMS OF THE COBALT(III) COMPLEX WITH THE LIGANDS 2-AMINOETHYL 3-AMINOPROPYL SULFIDE AND 1,1,1-TRIS(AMINOMETHYL)ETHANE

The new sulfur-bonded compound [Co(tame)( aeaps )] Cl3.H2O has been synthesized by the reaction of aeaps with Co(tame)Cl3 [tame = 1,1,1-tris( aminomethyl )ethane, and aeaps = 2- aminoethyl 3-aminopropyl sulfide or 3-thiahexane-1,6-diamine]. The Co(tame)( aeaps )3+ ion equilibrates in basic solution with the corresponding carbon-bonded species: Co(tame)( aeaps )3++HO-↔ Co(tame)(C-aeaps )2++H2O A salt of the carbon-bonded species, [Co(tame)(C- aeaps )](S2O6), has been isolated and its structure solved by X-ray diffraction analysis ( C- aeaps = 1,6-diamino-3-thiahexan-4-ide). The crystals are orthorhombic, Pna21, with cell dimensions a 20.455(10), b 9.960(10), c 8.982(10) Ǻ at 122(2) K. Preliminary thermodynamic and kinetic data are similar to the recently reported values for the corresponding coordination ion Co( tacn )( aeaps )3+ ( tacn = 1,4,7-triazacyclononane). In basic solution the Co(tame)( aeaps )3+ species exchanges one of its methylene protons orders of magnitude faster than any other methylene protons and also much faster than it forms the alkyl complex as shown by 13C n.m.r. measurements.

Conformational analyses of the isomers of the systems [Co(men)n(en)3-n]3+(men =N-methylethane-1,2-diamine, en = ethane-1,2-diamine; n= 1–3)

A molecular mechanics study of the configurational/conformational isomers of the system Λ-[Co(men)(en)2]3+(men =N-methylethane-1,2-diamine, en = ethane-1,2-diamine)(16 isomers), and the geometric/configurational/conformational isomers of the systems Λ-[Co(men)2(en)]3+(72 isomers) and Λ-[Co(men)3]3+(88 isomers) has been undertaken using the MM2 force field. Calculated steric energies (adjusted for statistical factors) are used to predict isomer ratios in the three systems, which are compared with experimentally determined themodynamic stabilities. Comparisons are also made between calculated geometries and X-ray molecular structures where these are available. For the Λ-[Co(men)2(en)]3+ system the calculations not only correctly predict the order of stability of the three possible geometric isomers, but also the most stable conformation for each of these cases. For the Λ-[Co(men)3]3+ system the two most stable forms observed experimentally are among the three forms of the molecule (of the 88 possible) calculated to be the most stable. Comparison of the geometric parameters for the two crystal structures and corresponding energy-minimized structures shows that the agreements are very good. The significance of statistical factors in thermodynamic comparisons of this type is discussed.

Conformational analyses of the isomers of the [Co{(±)pm}n(en)3−n]3+systems: a reinvestigation (en=ethane-1,2-diamine; pn=propane-1,2-diamine; n=0—3)

Abstract A molecular mechanics study of the isomers of [Co(pn) n (en) 3−n ] 3+ ( n =0-3) is reported. The MM2 force field has been parameterized for cobalt(III) amine complexes and the complete set of stereoisomers of the title complexes has been modelled. Detailed structural and thermodynamic comparisons are made with previous calculations on these systems and with experimental data. Structural details were satisfactorily modelled by MM2, and the correspondence between the calculated isomer ratios and those observed experimentally is excellent. The significance of statistical factors in thermodynamic comparisons of this type is discussed.