Designer ligands . Part 11 . 1 Electron-ionisation mass spectrometric studies of polydentate malonamide-derived ligands

Metal-selective ligands have obvious potential in solvent extraction applications, and Paiva has reviewed numerous examples of silver-selective systems. In our own investigations, aimed at developing ligands capable of extracting silver(I) selectively from ore-leach solutions containing base-metal contaminants, various design criteria were identified. Thus, the target ligands were expected to:i) contain a suitable combination of donor atoms, such as nitrogen, sulfur and oxygen, to effect selective and efficient solvent extraction of the metal; ii) be accessible via simple, efficient and cost-effective synthesis; iii) be capable of extracting the metal ions efficiently at low pH; and iv) be relatively inert towards acids. Substituted malonamides were expected to satisfy these criteria, and we have recently reported the microwave-assisted synthesis of series of polydentate malonamide derivatives, designed to effect tetra-coordinate chelation of silver(I). We now discuss the results of electron-ionisation (EI) mass spectrometric studies of these and related ligand systems.


Introduction
Metal-selective ligands have obvious potential in solvent extraction applications, 2 and Paiva 3 has reviewed numerous examples of silver-selective systems.In our own investigations, aimed at developing ligands capable of extracting silver(I) selectively from ore-leach solutions containing base-metal contaminants, various design criteria were identified.Thus, the target ligands were expected to:i) contain a suitable combination of donor atoms, such as nitrogen, sulfur and oxygen, to effect selective and efficient solvent extraction of the metal; ii) be accessible via simple, efficient and cost-effective synthesis; iii) be capable of extracting the metal ions efficiently at low pH; and iv) be relatively inert towards acids.Substituted malonamides were expected to satisfy these criteria, and we have recently reported the microwave-assisted synthesis of series of polydentate malonamide derivatives, designed to effect tetra-coordinate chelation of silver(I). 4We now discuss the results of electron-ionisation (EI) mass spectrometric studies of these and related ligand systems.

Results and Discussion
Access to the malonamides was achieved via amidation of diethyl malonate 1 and its alkylated derivatives 2b-j (Scheme 1).Alkylation 5 of the sodium enolate of diethyl malonate 1 with selected alkyl halides (RX) afforded the alkylated derivatives 2b-j in yields ranging from 47 to 83%. 1 H and 13 C NMR analysis of these esters revealed the presence of both keto and enol tautomers in CDCl 3 solution, the former being dominant under these conditions.Treatment of diethyl malonate 1 and its C-alkylated dervatives 2b-j with ethanolamine 6 at room temperature (for periods of between 2 and 168 hours) gave the corresponding N,N'-bis(2hydroxyethyl)malonamides 4a-j (Table 1).The products, some of which appear to be new, were all characterised by elemental (high-resolution MS) and spectroscopic (IR and 1 H and 13 C NMR) analysis.Formation of the amides was clearly evident from a comparison of their 1 H NMR spectra with those of their ester precursors.The methyl triplet (at δ ca.1.2 ppm) and the methylene quartet (at δ ca.4.1 ppm), characteristic of the ethyl esters, is replaced by two quartets at ca. 3.1 and 3.4 ppm (due to the ethylene protons) and two triplets at ca. 4.7 and 8.0 ppm (assigned to the hydroxyl and amide protons, respectively).Unlike their ester precursors 2a-j, the diamides 3a-j exhibit no 1 H NMR evidence of the enol tautomers.The microwave-assisted synthesis of the more complex N,N'-disubstituted analogues 4k-p has been reported elsewhere. 4hese latter compounds proved to be significantly more efficient ligands, than compounds 4a-j, for extracting silver(I) from low-pH solutions containing the base metals, copper and lead.With the ligands 4a-p in hand, the opportunity was taken to explore the major electronionisation mass fragmentations exhibited by representative systems.The fragmentation patterns proposed for the malonamides 4j and 4l (Schemes 2 and 3) are based on the high-resolution electron-impact (EI) and B/E linked-scan data, and correlations between the fragmentation of these compounds and related systems are summarised in Scheme 4.
In the mass spectrum of the heptylmalonamide 4j (Scheme 2), initial fragmentation of the molecular ion (m/z 288) proceeds via sequential loss of radical species (HΧ, HCOΧ and HΧ) to afford fragments with m/z 287, 258 and 257, respectively.The B/E linked-scan data also reveal a weak peak corresponding to the fragmentation, m/z 288 → 258.Further fragmentation of the odd-electron species (m/z 258) affords access to fragments formulated as a radical-cation (m/z 160), an iminium cation (m/z 173) and the acylium cations (m/z 130 and 112).Dealkylation of the resonance-stabilised cation (m/z 257) also affords the conjugated iminium cation (m/z 173), while loss of CH 2 =NH leads to an acylium cation (m/z 228), which is responsible for the base peak.The latter fragment (m/z 228) also appears to be formed directly from the molecular ion and from the odd-electron species (m/z 258).The molecular ion (m/z 402; Scheme 3) for N.N'-bis(benzylthioethyl)malonamide 4l, which shows exceptional selectivity for the extraction of silver(I), 4 exhibits initial elimination of radical and/or neutral species to give an even-electron ion (m/z 311) and a pair of odd-electron fragments (m/z 280 and 252).Sequential fragmentation of the monosubstituted malonamide species (m/z 252) leads to the acylium cations (m/z 236 and 112).Not surprisingly, certain fragmentations are characteristic of the benzylthioethyl moiety (e.g., m/z 402 → 311 → 151); the even-electron species (m/z 151) is also produced by fission of the fragments with m/z 252 and 236.Fission of the acylium cation (m/z 236) affords the tropylium cation (m/z 91), which is responsible for the base peak in this case.Fragment types common to all of the "alkyl spacer" compounds examined are illustrated in Scheme 4. The common fragmentations of the malonamides 4a, j-l (Scheme 4) appear to involve loss of a radical species R 1 • from the molecular ion I to give a resonance-stabilised cation II, which undergoes sequential fission to yield acylium cations of types III and IV.These fragmentation patterns were observed regardless of the nature of the substituents R 1 and R 2 .
The fragmentation patterns exhibited by the "aromatic spacer"-containing compounds 4m-o, however, are significantly different from those of the "alkyl spacer" analogues 4a, j-l.Acylium ions, typically detected in the mass spectra of the latter, appear to be absent in the spectra of compounds 4m-o.Specific fragmentations proposed for the malonamide derivative 4m are detailed in Scheme 5, while common fragments identified in the mass spectra of the ligands 4mo are summarised in Scheme 6.The molecular ion for compound 4m (m/z 314; Scheme 5) undergoes:i) loss of MeO•, presumably via sequential elimination of HCHO and H•, 8 to afford an even-electron species (m/z 283); and ii) fission of the malonamide skeleton to give two, odd-electron species (m/z 165 and 123).The latter fragment (m/z 123) is responsible for the base peak.Fission of the carbocation (m/z 283) also affords the acetanilide radical-cation (m/z 165) as well as the ortho-quinonoid cation (m/z 150).Loss of MeO• from the radical-cation (m/z 165) and demethylation of the omethoxyaniline species (m/z 123) then account for the formation of the acetanilide cation (m/z 134) and the ortho-quinonoid fragment (m/z 108), respectively.The latter fragment also appears to be produced via loss of ketene from the odd-electron species with m/z 165.

*
Comparison of the mass spectra of compounds 4m-o reveals the loss of MeO• or MeS• from the molecular ion V (Scheme 6) to afford the corresponding even-electron species VI.Both ion types (V and VI) fragment further to give odd-electron species of type VII, which, in turn, undergo demethylation to yield the ortho-quinonoid cations of type VIII.Apart from the elimination of MeO• from the molecular ion (m/z 342; Scheme 7) to afford a cation (m/z 311; cleavage 'a'), N,N'-bis(2-methoxybenzyl)malonamide 4p exhibits somewhat different fragmentation patterns from compounds 4m-o.Thus, fission ('b' and 'c') of the malonamide back-bone affords resonance-stabilised benzylic carbocations (m/z 221 and 136).The former (m/z 221) fragments to give a carbamoyl-type cation (m/z 162; cleavage 'd'), which then appears to lose C 2 HNO 2 , via an unusual intramolecular rearrangement, to afford the tropylium cation (m/z 91).Elimination of CH 2 =NH from the cation (m/z 136) provides access to an even-electron species (m/z 107).From the foregoing analyses, it is apparent that, while the systems examined exhibit certain common fragmentations, the overall patterns tend to be compound specific.

Experimental Section
General Procedures.Infrared spectra were recorded on Perkin-Elmer Spectrum 2000 spectrophotometer.NMR spectra were recorded on a Bruker 400MHz AVANCE spectrometer, and chemical shifts are reported relative to TMS.Low resolution mass spectra were obtained on a Hewlett-Packard 5988A mass spectrometer, and high resolution and B/E linked scan analyses on a VG70-SEQ double-focussing magnetic sector instrument (Cape Technikon Mass Spectrometry Unit); FAB mass spectra were obtained on a VG Micromass 70-70E spectrometer (Iontech B11N FAB-gun), using Xe as the bombarding gas and m-nitrobenzyl alcohol as the matrix (University of Potchefstroom).
The malonic esters 2b-k and the malonamides 4a-f are known compounds; the remaining malonamide derivatives appear to be new.The synthesis of the esters 2 and amides 4 are illustrated by the following examples.
Proposed fragmentations (*supported by the B/E linked-scan data) and the corresponding HRMS and relative abundance data for the malonamide derivative 4p.