Synthesis of Schiff Bases Derived from the Ammoniaundecahydro-closo-dodecaborate(1−) Anion, [B₁₂H₁₁NHCHR]^-, and Their Reduction into Monosubstituted Amines [B₁₂H₁₁NH₂CH₂R]^-:  A New Route to Water Soluble Agents for BNCT

Abstract

The reaction of [B12H11NH3]-, the amino derivative of the closo-dodecaborate anion, with aldehydes in methanol in the presence of catalytic amounts of alkali gives N-protonated Schiff bases [B12H11NHCHR]- (R = C6H5, 2-C6H4OMe, 4-C6H4OMe, 4-C6H4SMe, 4-C6H4NMe2, 4-C6H4NHCOMe, 4-C6H4CN, 4-C6H4Br, 4-C6H4Cl, 3,4-C6H3O2CH2, 1-C10H7, 2-C10H7, CHCHMe, CHCHPh). Reduction of the Schiff bases with NaBH4 in aqueous 2-propanol gives quantitatively the corresponding monoalkylamino derivatives [B12H11NH2CH2R]- (R = 2-C6H4OMe, 3,4-C6H3O2CH2, 4-C6H4NHCOMe, 4-C6H4CN). closo-Dodecaborate derivatives containing amino, carboxy, and isothiocyanate functions on aromatic rings, [B12H11NH2CH2C6H4-4-NH2]-, [B12H11NH2CH2C6H4-4-COOH]-, and [B12H11NH2CH2C6H4-4-NCS]-, were prepared. Functionalized derivatives of the [B12H12]2- anion can be used in BNCT and as a linker for iodination and astatination of biomolecules for radioimmunodetection and for radioimmunotherapy. The structures of Schiff bases (Bu4N)[B12H11NHCHC6H4-4-NMe2]*CHCl3 (I) and (Bu4N)[B12H11NHCHC6H4-2-OMe] (II) were determined by single-crystal X-ray diffraction. I crystallizes in the monoclinic space group P21/c with Z = 4 and unit cell dimensions a = 11.465(6) Å, b = 21.314(7) Å, c = 16.625(6) Å, β = 101.38(3)°. Crystals II belong to the monoclinic space group P21/c system, a = 10.282(2) Å, b = 20.272(5) Å, c = 17.052(3) Å, β = 105.31(2)°, Z = 4. The trans configuration of the protonated imino group was established (B−N = 1.517(7) and 1.525(4) Å, N−Cim = 1.274(6) and 1.274(3) Å, Cim−Car = 1.421(7) and 1.437(4) Å, for I and II, respectively). A strong intramolecular hydrogen bond between the imine hydrogen and the methoxy oxygen in the ortho position of the benzene ring (N···O = 2.714(4) Å, N−H = 0.93(2) Å, HN···O = 1.98(2) Å, N−H···O = 135(2)°) was found in II.

N‐Alkylation of Ammonioundecahydro‐closo‐dodecaborate(1–) for the Preparation of Anions for Ionic Liquids

“…Monobenzyl derivative 10 was first obtained by Sivaev et al [17] The nitrogen atom could be alkylated under standard conditions. In contrast to the alkylation with benzyl chloride, which stopped at dibenzyl derivative 5l, alkylation proceeded to afford trisubstituted ammonio derivative 11 (Scheme 4).…”

“…As previously found for this class of substances, and for other substances containing the dodecaborate cage, elemental analysis was erratic and unreliable. [13,19] N-Benzylammonioundecahydrododecaborate(1-) tetrabutylammonium salt (10) was prepared according to Sivaev et al [17] Melting points of the compounds are found in Table 1.…”

“…In the first route, a methyl substituent was introduced together with an ammonio group to afford 7 (Scheme 3). The second method involved the reduction of Schiff bases of 2 with benzaldehyde [17] to give monobenzyl derivative 10 (Scheme 4). In both of these routes, realkylation to a trisubstituted derivative was possible.…”

The use of closo-dodecaborate-containing linker improves targeting of HNSCC xenografts with radioiodinated chimeric monoclonal antibody U36

“…all chemicals were of analytical grade or better. daBi was prepared at our laboratories as previously described (22). cMab u36 (centocor BV, leiden, The Netherlands), an antibody that recognises the CD44v6 epitope on the outer cell surface (23), was used.…”

Polyhedral Boranes for Medical Applications: Current Status and Perspectives

“…[10] The first includes the introduction of a primary substituent (-OH, -SH, -NH 2 ) followed by modification of this substituent by using standard methods of organic chemistry. [11][12][13] The second approach is based on the preparation of cyclic oxonium derivatives of closo-dodecaborate followed by ring opening with various nucleophilic reagents. [14] This method is very efficient for the synthesis of derivatives with pendant functional groups connected to the boron cage through flexible spacers of 5-6 atoms and can be successfully applied to other types of polyhedral boron hydrides.…”