Carbon-Substituted Amines of the Cobalt Bis(dicarbollide) Ion: Stereochemistry and Acid-Base Properties

Abstract

Organic amines are found to be abundant in natural living systems. They also constitute an inestimable family of building blocks available in drug design. Considering the man-made cluster [(1,2-C₂B₉H₁₁)₂-3,3'-Co(III)]^- ion (1-) and its application as an emerging unconventional pharmacophore, the availability of the corresponding amines has been limited and those with amino groups attached directly to carbon atoms have remained unknown. This paper describes the synthesis of compounds containing one or two primary amino groups attached to the carbon atoms of the cobaltacarborane cage that are accessible via the reduction of newly synthesized azides or via the Curtius rearrangement of the corresponding acyl azide. This substitution represents the first members of the series of azides and primary amines with functional groups bound directly to the carbon atoms of the cage. As expected, the absence of the linker along with the presence of the bulky anionic polyhedral ion leads to a significant alteration of the chemical and physicochemical properties. On a broader series of amines of the ion 1^- we have thus observed significant differences in the acidity of the amino groups, depending on whether these are attached to the carbon or boron atoms of the cage, or the C-substituted amines contain an aliphatic linker of variable length. The compounds are relevant for potential use as cobalt bis(dicarbollide) structural blocks in medicinal chemistry and material science. Our study includes single-crystal X-ray diffraction (XRD) structures of both amines and a discussion of their stereochemical and structural features.

Scheme 1. Synthesis of Amines and Other Products Using Reagents with Azido Groups

Conditions: i. BuLi, DME, −78° C; ii. TsN₃ in toluene −78 to 25° C, 16h, extraction, separation using RP chromatography; iii. NaBH₄/CoCl₂ in 50% MeOH, r.t., 2 h; iv. BuLi, DME, −78° C, then Me₃SiN₃ in toluene −78 to 25° C, extraction, RP chromatography.

Figure 1

From left to the right: Kohn–Sham HOMO orbital of COSAN, COSAN-azide (light blue and dark blue are referred to regions in which the HOMO function is negative and positive, respectively), and examples of the IBO orbitals (see the Computational Details section) classified as the 2c–2e (pink) pattern and 3c–2e (blue) pattern.

Figure 2

Crystal structure of Me₄N[(1-Me₃Si-1,2-C₂B₉H₁₀)(1′,2′-C₂B₉H₁₁)-3,3′-Co(III)] (Me₄N6) (ORTEP view, 30% probability level). The cation is omitted for clarity. Selected interatomic distances (Å) and angles (deg): Si1–C1 1.933 (11), C1–C2 1.640(13), C1′-C2′ 1.628(13), Co(3)-C1 2.127(14), Co(3)-C2 2.066(14), Co(3)-C1′ 2.075(13), Co(3)-C2′ 2.089(13), C1–B4 1.730(4), C1–B5 1.712(13), C1–B6 1.731(14), C1′-B4′ 1.700(15), C1′-B5′ 1.683(14), C1′-B6′ 1.705(14), C2–B7 1.720(14), C2–B11 1.686(14), C2–B6 1.714(14), Si1 C1 C2 119.3(6), C3 Si1 C1 110.2(4), C4 Si1 C1 107.9(4), C5 Si1 C1 114.6(4), Si1 C1 Co3 119.2(4), Si1 C1 B4 128.9(6), Si1 C1 B5 113.9(6), Si1 C1 B6 106.1(6), C3 Si1 C1 110.2(4), C4 Si1 C1 107.9(4), C5 Si1 C1 114.6(4), C2′ Co3 C1 101.1(4), C2′ Co3 B8 170.5(4), C2′ Co3 B4 128.8(4).

Scheme 2. Synthesis of Alkylazide and Triazole Derivatives of the Cobalt Bis(dicarbollide) Ion

The starting mesyl esters were prepared according to previously published procedures.^, Reaction conditions: i. NaN₃, DMF, r.t., 12 h; ii. Ph-alkyne, CuI, DIPEA, DMF, 40 °C.

Figure 3

Crystal structure of the rac-isomer of Me₄N10 (ORTEP view, 30% probability level). Selected interatomic distances [Å] and angles [°]: C4 N1 1.483(4), N1 N2 1.241 (4), N2 N3 1.138 (4), C4A N4 1.490 (4), N4 N5 1.243 (4), N5 N6 1.127(4), C3 C4 1.522(4), C1 C3 1.534 (4), C1 C2 1.623(4), C1 B4 1.732(4), C1 B5 1.711(4), C1 B6 1.742(4), C1 Co3 2.116 (3), C2 B11 1.720(4), C2 B7 1.701(4), C2 Co3 2.088(3), Co3 C1A 2.129(3), Co3 B4 2.100(3), Co3 B4A 2.094(3), Co3 B7 2.114(3), Co3 B7A 2.118(3), Co3 B8 2.122(3), Co3 B8A 2.112(3), N1 N2 N3 172.9(3), N1 N2 N3 172.9(3) C2 C1 C3 117.8(2), B4 C1 C3 124.9(2), C3 C4 N1 110.7(2), C4 N1 N2 114.1(2), C2 C1 C3 117.8(2), C3 C4 N1 110.7(2), C4 N1 N2 114.1(3), C4A N4 N5 114.091(3) C3A C4A N4 111.2(3).

Figure 4

Crystal structure of Me₄N11 (ORTEP view, 30% probability level). The Me₄N⁺ cation and solvent molecule have been omitted for the sake of clarity. Selected interatomic distances [Å] and angles [°]: C3 N1 1.464(2), N1 C5 1.346(2), N1 N2 1.341(2), N2 N3 1.317(2), N3 C4 1.360(2), C4 C6 1.376(2), C2 C1 1.531(2), C5 N1 1.346(2), C1 C2 (cage) 1.619(2), C1 B5 1.710(2), C1 B4 1.731(2), C1 B6 1.754(2), C1 Co3 2.103(1), C2 B11 1.702(2), C2 B6 1.732(2), C2 Co3 2.068(1), Co3 C1A 2.053(1), Co3 B4A 2.091(2), Co3 B4 2.089(2), Co3 B7 2.092(2), Co3 B7A 2.108(2), Co3 B8A 2.118(2), Co3 B8 2.101(2), N1 N2 N3 107.21(12), N2 N1 C3 119.22(12), C3 N1 C5 129.82(12), C4 N3 N2 109.18(12), Co1 C1 C2 112.80(12), B5 C1 C2 122.05(9), B6 C1 C2 109.92(11), C1 Co3 C1A 103.40(), C1 Co1 C2A 134.52(5), B4 C1 C2 126.80(11).

Figure 5

Crystal structure of Me₄N12 (ORTEP view, 30% probability level). The Me₄N⁺ cation is omitted for clarity. C5 N1 1.463(3), N1 C6 1.348(3), N1 N2 1.345(2), N2 N3 1.315(3), N3 C7 1.371(3), C4 C5 1.515(3), C1 C2 1.643(3), C6 N1 1.348(3), C2 C3 1.536(3), C2 B11 1.720(3), C1 B4 1.720(3), C2 B6 1.734(3), C1 Co3 2.045(2), C1 B5 1.703(3), C1 B6 1.721(3), C2 Co3 2.100(2), Co3 C1A 2.060(2), Co3 B4A 2.097(2), Co3 B4 2.083(2), Co3 B7 2.103(2), Co3 B7A 2.102(2), Co3 B8A 2.123(2), Co3 B8 2.110(2), N1 N2 N3 107.38 (17), N2 N1 C5 120.99(17), C5 N1 C6 128.36(18), N1 C6 C7 105.36(18), Co3 C1 C1A 134.75(8), C1 C2 B5 112.13 (16), C3 C2 Co3 112.81(14), C2 Co3 C2A 102.51(8), C1 Co1 C1A 134.75(8), C2 C1 B4 113.47(16).

Scheme 3. Alternative Synthesis of the Monosubstituted Amine 4^–via Curtius Rearrangement

Conditions: i. dioxane, SOCl₂, 3 h ii. dioxane-water, NaN₃, 16 h, extraction, RP chromatography; iii. and iv. dioxane, 1 M HCl, 100° C, 12 h, extraction, RP chromatography. # Intermediate products that could not be isolated.

Figure 6

Crystal structure of the anionic form of the amine Me₄N4 (ORTEP view, 30% probability level). Selected interatomic distances [Å] and angles [°]: C1 N1 1.436(9), C1 C2 1.653(9), C1A C2A 1.613(9), C1 B4 1.716(11), C1A B4A 1.710(10), C2 B7 1.718(9), C2A B7A 1.705(10), C1 B5 1.701(11), C1 B6 1.727(10), C1A B6A 1.733(10), C2 B6 1.713(10), C2A B6A 1.720(11), C1 Co3 2.077(7), C1A Co3 2.044(7), C2 B11 1.702(10), C2 Co3 2.049(6), C2A Co3 2.0431(7), Co3 B4 2.089(7), Co3 B7 2.102(7), Co3 B7 2.097(4), Co3 B7 2.081(7), Co3 B8 2.105(8), Co3 B8A 2.115(7), B9 B12 1.803(9), C2 C1 N1 116.6(5), N1 C1 B6 110.7(5), N1 C1 B5 119.5(6), N1 C1 B4 126.7(5), C1 Co3 C1A 128.2(3), C2 Co3 C2A 100.8(3), C1 C2 B7 112.4(5), C1 C2 B11 112.1(5), B5 C1 Co3 123.2(5), B4 C1 B6 114.3(5).

Figure 7

Crystal structure of the protonated form of the diamine Me₄N5.HCl (ORTEP view, 30%). The solvating acetone molecule and the Me₄N⁺ cation have been omitted for clarity. Selected interatomic distances [Å] and angles [°]: C1 N1 1.466(4), C1A N2 1.442(4), C1 C2 1.621(4), C1A C2A 1.639(4), C1 B4 1.698(5), C1A B4A 1.703(5), C2 B7 1.716(5), C2A C7A 1.714(5), C1 B5 1.696(5),1.711(5), C2 Co3 2.064(3), C1A Co3 2.103(3), Co3 B4 2.102(4), Co3 B7A 2.073(4), Co3 B7 2.093(4), Co3 B8 2.119(4), Co3 B8A 2.108(4), C2 C1 N1 119.1(3), C2A C1A N2 117.6(3), N1 C1 B4 122.0(3), N2 C1A B4A 124.8(3), N1 C1 B6 111.1(3), N2 C1A B6A 111.4(3), N1 C1 B5 115.1(3), N2 C1A B5A 118.4(3), C1 Co3 C1A 104.46(13), C1 Co3 C2A 104.28(13), C2 Co3 C2A 137.17(13), C1 C2 B7 112.1(3), C1A C2A B7A 112.8(2).

Figure 8

Chiral HPLC separations of the enantiomers of ions 4^– (A) and 5^– (B). The enantiomers were detected by UV (blue trace) and CD (black trace) detection at wavelengths of 290 and 281 nm, respectively.

Chart 1. Schematic Structures of the Compounds Studied for the Determination of Proton Dissociation Constants