Scientific paper
Design, Synthesis, Characterization and Complexation Studies of Novel Vanadophiles: Calix[4]pyrrole Hydroxamic Acids
Kejal P. Jayswala and Jigar R. Patela,b*
a Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad-380009, Gujarat, India.
b Navrang Chemicals, L78-GIDC, Odhav, Ahmedabad, Gujarat, India.
* Corresponding author: E-mail: jigarvirdia@gmail.com, Tel.: +91-9879290447
Received: 07-09-2007
Abstract
New four armed calix[4]pyrrole bearing four hydroxamic acid groups (C4PHA) have been synthesized by reacting partially reduced mesotetramethyl-mesotetra (p-nitrophenyl) calix[4]pyrrole with different aromatic acid chlorides (ben-zoyl chloride, p-nitrobenzoyl chloride, cinnamoyl chloride, phenyl acetyl chloride and p-chlorobenzoyl chloride) at low temperature. Synthesized compounds were characterized by elemental analysis, FT-IR, NMR and Mass data. Extraction studies showed that synthesized ligands exhibit high affinity and selectivity for vanadium(V), especially 3e. Thus, various significant extraction parameters like pH, concentration of vanadium(V), reagent (ligand) concentration and solvent effects were optimized for 3e. The results of extraction studies with 3e, (using optimized procedure) were very encouraging, hence, the extraction experiments were further extended to natural and industrial samples in presence of diverse ions. The stoichiometry of vanadium-C4PHA (3e) complex was determined by slope-ratio method using UV-Visible spectrophotometry and the results were validated by ICP-OES analysis. Transportation studies of vanadium(V) across a liquid membrane containing C4PHA (3e) in a three-phase system were carried out in a specially fabricated glass assembly under controlled conditions and the mechanism of metal-ion transport has been explained.
Keywords: Calix[4]pyrrole, hydroxamic acid, vanadium, liquid-liquid extraction.
1. Introduction
Vanadium is a trace element of highly critical role in biochemical processes and of significant importance in environmental, biological and industrial analysis due to its toxicity.1'2 Several methods have been proposed for the determination of vanadium, mainly based on the liquid-liquid extraction technique followed by spectrophotometry.3-6 These methods although sensitive, are not selective especially for real sample analysis. Thus, highly sensitive and selective methods are still required for trace analysis of vanadium in different kinds of samples, especially environmental samples.
Calixpyrroles, have been extensively studied as powerful building blocks to furnish functional receptors for ionic and molecular recognition.7-9 Calix[4]pyrroles possess four pyrrole units assembled in a calixarene like manner, replacing phenolic units, and display conformational behavior similar to that of the calix[4]arenes. Easy con-
struction of calixpyrroles with pre-designated core size and ligand location widens the scope of their applicability for design of ion-selective receptors.10-13 Hydroxamic acids, on the other hand, are versatile extractants and they
Figure 1: (a) Schematic complexation of vanadium with a pair of hydroxamic acids (b) Metal complexation by a pair of ligands pre-organized on a 1,2-alternate scaffold
have achieved significant importance as analytical tools for the separation and determination of a large number of metal-ions; especially as a selective/specific reagent for the determination of vanadium(V) metal-ion.14,15 In recent years, calixarene with hydroxamic acid as a functional group have been synthesized and used for the complexa-tion studies.16-18
With this in view, we have designed, synthesized and characterized novel calix[4]pyrrole derivatives containing hydroxamic-acid chelating sites attached to all four meso-positions. The basis of the design process is a well known fact19 that in ca. 6N acid solution vanadium exists as VO2+ species which is readily co-ordinated by a pair of hydroxamic acid functionality as [VO2+{C (=0)N(-0)-}2]+ (Figure 1a). The calix[4]pyrrole derivative 1 chosen as the platform exists in 1,2-alternate conformation (i.e. the phenyl residues on meso position are in 1,2-alternate conformation). This means if the phenyl rings can be manipulated to accommodate hydroxamic acid moiety, two pairs of hydroxamic acid chains on each side of the molecular plane can be achieved, which can simultaneously complex two va-nadyl ions (Figure 1b). The proposed pre-organization of the ligands was manifested by first partially reducing the nitro functionality on each phenyl ring (anchored to meso positions) to hydroxylamine and coupling it with suitable acylchloride. The hydroxamic acid derivatives prepared in this way were examined for vana-
dium complexation and were found to be excellent reagents for detection, determination and separation under optimized conditions.
2. Experimental
2. 1. General
Melting points were taken in a single capillary tube using a Toshniwal (India) melting point apparatus and were uncorrected. Elemental analysis was done on Heraeus CarloEbra 1108 elemental analyzer. IR spectra were recorded on FTIR-410 ratio recording Jasco Infrared spectrophotometer as KBr pellets and expressed in cm-1. 1H NMR spectra were recorded on DRX 300 operating at 300 MHz for proton in DMS0-d6 with tetramethylsilane as internal standard. Mass Spectra were recorded on JEOL SX 102/DA 6000 mass spectrometer using xenon/argon (6KV/10KV, 10mA) as the FAB-gas. UV-Visible spectro-metric studies were carried out on a JASCO 570 UV/VIS/NIR Spectrophotometer.
2. 2. Synthesis
Synthesis of meso-tetramethyl-meso-tetra-(p-ni-trophenyl)-calix[4]pyrrole 1 was carried out with previously reported procedure.20 Further proceedings were done according to Scheme 1.
Scheme 1: Synthetic route for 3a-e
2. 2. 1. Procedure for partial reduction of 1
1 (5 g, ca. 10 mM) was dissolved in chloro-form:THF (1:1, 100 mL), added with a solution of NH4a (5 g) in water (100 mL) and stirred for 10 min with aid of magnetic stirrer. Zn powder (7 g) was then added in small portions (0.3-0.5 g) after every 5 min until the reduction was complete. After additional stirring of 15min the contents were allowed to cool to ambient temperature. Organic layer was collected, dried with MgSO4 and concentrated under vacuum until pale yellow crystals of hydroxyla-mine were observed. The concentrate along with crystals was cooled to -10 °C and filtered instantaneously over a glass frit with aid of vacuum. Yield was 58%. As aromatic hydroxylamines are very unstable in air, the product 2 was re-dissolved in dry chloroform and kept at low (0-4 °C) temperature until coupled with acylchlorides.
30H ArH), FAB MS m/z 1272 (M-1), Anal. calcd for C80H72N808: C 75.47, H 5.66, N 8.80. Found: C 75.58, H 5.^0,]N ^.81.
3d: Yield 73%, mp 160 °C, IR (KBr): v 3400 cm-1 (-0H), 854 cm-1 (N-0), 1H NMR (500 MHz, DMS0-d6) : 5 1.96 (s, 12H, CH3), 7.62-7.82 (d, 16H, C4P ArH), 7.29(s, 4H, Pyrrole NH), 5.84-5.89 (s, 8H, Pyrrole aromatic), 8.80 (s, 4H, N-OH), 7.50-7.59 (m, 30H, ArH), FAB MS m/z 1354 (M-1), Anal. calcd for C76H60N8O8a4: C 67.35, H 4.43, N 8.27. Found: C 67.30, ìì 4.^40, N 8.20.
3e: Yield 74%, mp 180 "C, IR (KBr): v 3401 cm-1 (-OH), 863 cm-1 (N-0), 1H NMR (500 MHz, DMS0-d6) : 5 1.97 (s, 12H, aH3), 7.61-7.76 (d, 16H, a4P ArH), 7.29 (s, 4H, Pyrrole NH), 5.84-5.89 (s, 8H, Pyrrole aromatic), 8.81 (s, 4H, N-OH), 7.26-7.62 (m, 30H ArH), FAB MS m/z 1396 (M-1), Anal. calcd for a7gHg0N12O1g: C 65.33, H 4.29, N 8.02. Found: C 65.29, H 44.21, N 8.0.
2. 2. 2. General Procedure for Coupling
The partially reduced nitro derivative 2 (ca. 10 mM in 100 mL chloroform) was covered with saturated solution of NaHCO3 and cold acylchloride of choice (ca. 45 mM in dry chloroform) was added drop wise directly into lower layer with slow stirring. After the addition was complete (ca. 30 min), the stirring was continued faster for another 30min. The organic layer was collected and washed with water, concentrated to 1/5'h with flash evaporator and acetone was added drop wise until precipitation of brown powder was complete. The brown powder (products 3a-e, depending upon acylchloride employed) was collected and purified by re-crystallization from ethyl acetate. Yield 70-74%.
2. 3. Characterization Data
3a: Yield 70%, mp 180 "C, IR (KBr): v 3402 cm-1 (-OH), 859 cm-1 (N-O), 1H NMR (500 MHz, DMSO-d6) : 5 1.96 (s, 12H, aH3), 7.62-7.82 (d, 16H, a4P ArH), 7.29 (s, 4H, Pyrrole NH)3, 5.84-5.89 (s, 8H, Pyrrole aromatic), 8.80 (s, 4H, N-OH), 7.42-7.50 (m, 30H, ArH), FAB MS m/z 1215 (M-1), Anal. calcd for a7gHg4N8O8: C 75.0, H 5.26, N 9.21. Found: C 74.98, H 5.30, N 9.41.
3b: Yield 72%, mp 166 "C, IR (KBr): v 3395 cm-1 (-OH), 860 cm-1 (N-O), 1H NMR (500 MHz, DMSO-d6) : 5 1.96 (s, 12H, aH3), 7.60-7.72 (d, 16H, a4P ArH), 7.30 (s, 4H, Pyrrole NH)3, 5.84-5.89 (s, 8H, Pyrrole aromatic), 8.80 (s, 4H, N-OH), 4.68-4.76 (d, 8H, aH=aH), 7.82-7.91 (m, 30H, ArH), FAB MS m/z 1320 (M-1), Anal. calcd for a84H72N8O8: C 76.36, H 5.45, N 8.48. Found: C 75.98, H 5.30, NN 8.41.
3c: Yield 70%, mp 183 "C, IR (KBr): v 3409 cm1 (-OH), 866 cm-1 (N-O), 1H NMR (500 MHz, DMSO-d6) : 5 1.99 (s, 12H, aH3), 7.42-7.50 (d, 16H, a4P ArH), 7.29 (s, 4H, Pyrrole NH)3, 5.84-5.89 (s, 8H, Pyrrole aromatic), 8.82 (s, 4H, N-OH), 3.75 (s, 8H, COCH2), 7.66-7.72 (m,
2. 4. Analytical Studies
For complexation studies, stock solutions of ligands 3a-e (7.1 x 10-2 M) were prepared by separately dissolving appropriate amounts of each in 1L of ethyl acetate. The vanadium stock solution (4.9 x 10-2M) was prepared by dissolving requisite amount of ammonium metavanadate in 5 mL conc. HCl and diluting to 1 L with 6 M HCl. The stock solutions were further diluted 100 folds to obtain working solutions of (7.1 x 10-4 M) and (4.9 x 10-4 M) for ligands and vanadium respectively. For extraction studies, appropriate volumes of ligand and metal solutions were mixed (as per requirement of the experiment, 1-10 mL), shaken for 10 min and separated through a separatory funnel. The organic layer was then dried with MgSO4 and diluted to 100 mL with appropriate solvent. Solutions thus prepared were examined for UV-Vis absorptions at suitable wavelengths. The quantitative results were validated by ICP-OES measurements at 309.31 nm emission line for vanadium. Natural and industrial test samples were prepared according to following procedure : 1 g sample was suspended in acid mixture (Hal:HNO3, 1:3 v/v) and evaporated to dryness thrice, dissolved in 15 mL concentrated hydrochloric acid along with 0.5 g of ammonium persulphate and diluted with distilled water to 100 mL. The natural samples were burnt on red-hot flame after first evaporation. Results of the study represent average values of 10 determinations.
3. Results and Discussion
All the synthesized calix[4]pyrrole hydroxamic acids 3a-e were tested for the extraction and spectropho-tometric determination of vanadium(V). Analytical studies were carried out by extraction of vanadium at acidic pH from aqueous to organic layer. It was found that among all the synthesized calix[4]pyrrole hydroxamic acids, 3e is the most sensitive reagent (Table 1). The maxi-
mum absorption for the pinkish violet vanadium: 3e complex was measured at 498 nm and showed a bathochromic shift of 238 nm from the reagent blank (260nm). Further, 3e being the most sensitive reagent, extraction studies and efforts for optimization of significant parameters were directed towards 3e.
Table 1: Comparative extraction ability of 3a-e (Experimental Details - Vanadium: 2 mL, 4.9 x 10-4 M; 3a-e: 10 mL, 7.1 x 10-4 M; HCl: 6 M; Solvent: Ethyl acetate)
Calix[4]pyrrole	^max	Molar absoptivity
Hydroxamic acids	(nm)	(l mol-1 cm-1)
3a	499	7.3 x 103
3b	499	9.4 x 103
3c	485	8.9 x 103
3d	497	1.3 x 104
3e	498	1.9 x 104
zene, dichloromethane and carbon tetrachloride (Table 2). Highest extractability of the complex was observed with ethyl acetate and thus it was deemed to be the most suitable solvent for quantitative extraction in the entire study.
3. 1. 3. Reagent Concentration
Extraction with various concentration of reagent showed that 7 mL of 0.1% 3e was sufficient for the quantitative extraction of vanadium (Table 3). Lower concentration resulted in incomplete extraction whereas higher concentration has no adverse effect on the extraction of vanadium.
Table 3: Effect of reagent (3e) concentration on extraction of vanadium (Experimental Details - Vanadium: 5 mL, 4.9 x 10-4 M; HC-l: 6 M; Solvent: Ethyl acetate; Xmax: 498nm)
3. 1. Effect of Variables on the Extraction
3. 1. 1. Acidity
Maximum extractability of vanadium-3e complex was obtained with 6M HCl, but as the concentration of acid solution decreases, the percentage extraction of vanadium also decreased (Figure 2), hence all the extractions were carried out at 6M HCl.
Figure 2: Effect of HCl concentration on the Vanadium-3e Com-plexation. (Experimental Details - Vanadium: 2 mL, 4.9 x 10-4 M; 3e: 10 mL, 7.1 x 10-4 M; Solvent : Ethyl acetate)
3. 1. 2. Solvent
The vanadium-3e complex was extracted with various solvents like ethyl acetate, chloroform, toluene, ben-
Table 2: Effect of Solvents on the extraction of Vanadium-3e complex (Experimental Details - Vanadium: 2 mL, 4.9 x 10-4 M; 3e: 10 mL, 7.1 x 10-4 M; HCl: 6 M; : 498nm)
Solvent	Extraction (%)
Toluene	17
CHCl3	28
Benzene	31
CH^Cl^	68
CHCl3	73
Ethyl acetate	100
mL of reagent	Molar absorptivity
(0.1% 3e)	em (L mol-1 cm-1)
10	1.91 x 104
9	1.90 x 104
8	1.91 x 104
7	1.91 x 104
6	1.62 x 104
5	1.31 x 104
4	0.97 x 104
3	0.72 x 104
2	0.55 x 104
1	0.27 x 104
3. 1. 4. Shaking Time
The optimum shaking time was found to be 5-6 min, which was sufficient for quantitative extraction of vanadium. The extraction was not affected by further shaking, indicating the equilibrium state for complexa-tion.
3. 2. Stoichiometry of the Complex
The composition of vanadium-3e complex extracted into ethyl-acetate was studied by 'Slope Ratio Method'. The absorbance (at Àmax) values were plotted against corresponding concentration for two set of observations. For the first set, the extraction was carried out by taking a fixed (excess) concentration of vanadium solution with varying amounts of 3e. For second set, the vanadium concentration was varied keeping 3e concentration fixed (in excess). The plot gave two straight lines defined by linear equations y=0.2731x-0.2513 (set I) and y=0.1365x-0.1257 (set II) (Figure 3). The ratio of the slopes found was 2.00, indicating that 1 mole of 3e co-ordinates with 2 moles of vanadium, i.e. the extracted species is [(VO2+)2(3e)-4]+2.
Figure 3: Slope ratio plot for stoichiometry (Experimental details -Fixed Concentration: 1.96 X 10-4 M (3e); HCl: 6 M; Solvent: Ethyl acetate; Xmax: 498 nm)
3. 3. Effect of Diverse Ions
Extraction of a single metal ion from a sample containing a variety of other ions gives an indication of potential sensitivity and selectivity of the ligand. Thus, an interference study was performed by extracting vanadium with 3e from a matrix containing controlled amount of potential interferences. The tolerance limit was set as the amount of foreign ion causing 2% change in quantification (recovery) of vanadium. The quantification was carried out with ICP-OES analysis of organic phase containing extracted complex. Table 4 summarizes results of 'diverse ion effect' studies.
Table 4: Tolerance limit for various ions in extraction of vanadium with 3e (Experimental Details - Vanadium: 5 mL, 1.96 X 10-3 M; HCl: 6 M; Solvent: Ethyl acetate; 498 nm; various ions were added in increments of 5mg at a time)
Ion	Added as	Tolerance limit (mg)
Ag+	AgNO3	40
Pb+2	Pb(NO3)2	45
Mn+2	MnCl2	40
Cu+2	CuCl2	50
Al+3	AlCl3	50
Cr+3	Cr2O3	40
La+3	La2O3	70
Ce+4	Ce(SO4)2	50
Mo+6	(NH4)6Mo7O24	25
UO2+2	uo2(no3)2	50
3. 4. Analysis of Real Samples
In addition to diverse ion effect, some natural and industrial samples collected from 'Vatva Industrial Area' (GIDC, Ahmedabad, Gujarat, India) were also tested to determine vanadium content with aid of 3e. The test samples were prepared as described in experimental section. Vanadium was extracted with 3e from the test samples and quantified by UV-Visible absorption analysis. The results obtained were compared with results of ICP-OES analysis for same samples. The summary is tabulated in Table 5.
Table 5: Vanadium found in natural and industrial samples
Sample	Concentration in ppm
Spectrophotometer ICP-OES
Tobaccoa	2.18	± 0.03	2.198
Lake water	1.05	± 0.01	1.060
Industrial effluent	1.80	± 0.02	1.802
Blood sampleb	0.02	± 0.01	0.021
Soil	0.09	± 0.01	0.088
a Tobacco sample was collected from a farm in vicinity of the said industrial area
b Blood sample was generously provided by a volunteer working in the said industrial area
3. 5. Liquid Membrane Transport Studies
Considerable effort has been directed for over two decades towards the transport of metal ions across liquid
a)
b)
c)
Figure 4: (a) Apparatus for transport studies (b) Transport Profile of vanadium across Liquid Membrane - ethyl acetate solution of 3e (c) Pictorial representation of transportation mechanism through liquid membrane
membrane. These liquid membranes are of interest for both, possible technological application and fundamental studies of the transport process. Transport of vanadium ion was carried out in a specially fabricated glass assembly as shown in the Figure 4a. The experimental setup was : Source Phase (SP): 14 mL, 7.16 x 10-4 M vanadium in 6M HCl; Liquid Membrane Phase (LMP):40 mL, 7.16 x 10-4M 3e in Ethyl Acetate; Receiving Phase (RP): 14 mL, 0.1 M HCl; Temp. 30 °C. The transport studies indicated very encouraging results especially t^ which is 15 min. indicating very fast transport of metal through the liquid membrane (Figure 4b).
Among the synthesized derivatives, 3e was found to be very much promising candidate for the purpose of complexation and thus can be used for pre-concentration and separation from diverse matrix. Figure 4c depicts the mechanism for transport of vanadium through a liquid membrane containing H4A (i.e. C4PHA).
4. Conclusion
In conclusion, calix[4]pyrrole based hydroxamic acids were synthesized and characterized. Their abilities for extraction of vanadium(V) were extensively studied and they were found to be very good extractants, in particular compound 3e (em: 1.9 x 104), for which, the extraction parameters were optimized with very encouraging results. Further, 3e was tested for sensitivity and selectivity in presence of various foreign ions (diverse ion effect/interference) and the extraction studies were further extended to real samples as well with very high accuracy, as compared (validated) with ICP-OES analysis. Liquid membrane transport studies were also carried out using ethyl acetate solution of 3e as liquid membrane. The transport studies indicated very encouraging results with very short transportation half-time (t,^: 15 min) indicating rapid transport of metal through the liquid membrane. The mechanism for the transport phenomena is explained.
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Povzetek
Pripravili smo nove kaliks[4]pirele s štirimi hidroksamskimi kislinami (C4PHA) in jih karakterizirali z elementno analizo, FT-IR, NMR in masno spektrometrijo. Spojine imajo visoko afiniteto in selektivnost kot ligandi pri ekstrakciji va-nadija(V). Ekstrakcijo smo testirali tudi na kompleksnih vzorcih, ki vsebujejo različne ione. Stehiometrijo kompleksa vanadija s 3e smo delečili s UV-vidno spektroskopijo in ICP-OES analizo. [tudirali smo tudi transport vanadija(V) skozi tekočo membrano, ki je vsebovala 3e.