Designer ligands. VIII. Thermal and microwave-assisted synthesis of silver(I)-selective ligands

Article abstract of DOI:10.1081/SCC-120013745

Thermal and microwave-assisted methods have been used for preparing multidentate malonamide derivatives as silver(I)-selective ligands, the latter methodology providing convenient and rapid access to the target compounds in yields of up to 92%. Metal extr

Full text of DOI:10.1081/SCC-120013745

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DESIGNER LIGANDS. VIII. THERMAL AND MICROWAVE-
ASSISTED SYNTHESIS OF SILVER(I)-SELECTIVE LIGANDS
a
b
André Daubinet & Perry T. Kaye
a
Department of Chemistry, Rhodes University, Grahamstown, 6140, South Africa
b
Department of Chemistry, Rhodes University, Grahamstown, 6140, South Africa
Published online: 16 Aug 2006.
To cite this article: André Daubinet & Perry T. Kaye (2002): DESIGNER LIGANDS. VIII. THERMAL AND MICROWAVE-ASSISTED
SYNTHESIS OF SILVER(I)-SELECTIVE LIGANDS, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 32:20, 3207-3217
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 20, pp. 3207–3217, 2002
DESIGNER LIGANDS. VIII. THERMAL
AND MICROWAVE-ASSISTED
SYNTHESIS OF SILVER(I)-SELECTIVE
LIGANDS
Andre
´
Daubinetand Perry T. Kaye *
Department of Chemistry, Rhodes University,
Grahamstown, 6140, South Africa
ABSTRACT
Thermal and microwave-assisted methods have been used for
preparing multidentate malonamide derivatives as silver(I)-
selective ligands, the latter methodology providing convenient
and rapid access to the target compounds in yields of up to
92%. Metal extraction studies revealed that some of the
ligands exhibit selectivity for silver (over the base metals,
copper and lead), ranging from moderate to excellent.
Key Words: Microwave-assisted synthesis; Silver(I) ligands
In research directed towards the development of metal-selective
[2,3]
[
1]
ligands, we have explored various molecular templates,
including sym-
[
4]
metrically substituted malonamides as EDTA analogues. The presence of
an active methylene centre and two acyl groups makes the malonyl system
an attractive template for the introduction of structural features necessary
*
Corresponding author. E-mail: p.kaye@ru.ac.za
207
3
DOI: 10.1081/SCC-120013745
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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3
208
DAUBINET AND KAYE
Figure 1. Structural features of the proposed silver(I)-selective ligands.
for metal-selective solvent extraction applications. These features, illustrated
in Fig. 1, include appropriate donor atoms and spacer groups as well
[
5]
as hydrophobic moieties to fine-tune lipophilicity. Iveson et al. have
0
recently reported N,N -disubstituted malonamides which exhibit potential
as lanthanide extractants and, in our investigation into the development of
silver(I)-selective ligands, we have prepared a series of novel, polysubstituted
malonamides and explored their potential for selectively extracting silver(I)
[
6]
from a low pH ore-stream containing base metals.
Access to the ligands 4a–c (Sch. 1; Table 1) was initially explored by
stirring diethyl malonate 1a with:- (i) 2-methoxyethylamine 2a in hexane; (ii)
S-benzylcysteamine (2b) hydrochloride in 0.1 M methanolic NaOMe; and
(
(
iii) neat o-anisidine 2c, at room temperature for 7 days. This approach
Method A) afforded each of the malonamides 4a and 4b in 24% yield,
but none of the o-anisidine derivative 4c; however, treatment of o-anisidine
with malonyl dichloride and pyridine in THF at room temperature over 24 h
(
increase the yields, the reactions were repeated at elevated temperature––an
Method B) gave the required malonamide 4c in 23% yield. In an attempt to
[
7]
approach reported to afford an allylmalonamide derivative in 50% yield.
When diethyl malonate 1a was reacted at reflux temperature with:- (i)
-methoxyethylamine 2a in MeOH and (ii) neat o-anisidine 2c (Method C),
2
the corresponding malonamides 4a and 4c were isolated in 62% and 66%
0
yield respectively (Table 1). N,N -Bis(2-methylsulfanylphenyl)malonamide
4d was obtained in 30% yield under similar conditions using neat 2-methyl-
sulfanylphenylamine 2d.
These results clearly left room for improvement and attention was
given to the use of microwave irradiation. While there has been some
[
8]
debate concerning the mechanisms involved, interest in microwave-assisted

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DESIGNER LIGANDS. VIII
3209
Scheme 1. Amidation of malonic esters (see Table 1 for reaction conditions).
Table 1. Yields Obtained for the Synthesis of the Malonamide Derivatives 4a–f
(
see Sch. 1)
a
b
Yield /%
Compd.
Product
Conditions
Rn.time
4
a
b
A
C
7 d
16 h
24
62
4
A
D
7 d
2.5 min
24
55
c
A
B
C
D
7 d
24 h
48 h
4.5 min
–
4
4
c
23
66
65
C
D
48 h
6 min
30
49
d
4
e
f
D
D
6 min
96
54
4
7.5 min
a
Conditions. Method A: Reaction of amine 2 with diethyl malonate 1a at room
temperature. Method B: Reaction of amine 2a with malonyl dichloride at room tem-
perature. Method C: Reaction of the amine 2 with diethyl malonate at reflux tempera-
ture. Method D: Microwave-assisted reaction of the amine 2 with diethyl malonate
b
c
1
a or diethyl allylmalonate 1b. Recrystallised material. No product isolated.

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210
DAUBINET AND KAYE
Figure 2. Percentage distribution of diethyl malonate 1a ^, monoamide 3c g and
the diamide 4c m as a function of time for: (a) thermal; and (b) microwave-assisted
reactions.
synthesis is growing rapidly and the methodology has been successfully
[
9]
applied in various reactions. For comparative purposes, the reactions
between neat diethyl malonate 1a and o-anisidine 2c under thermal (reflux)
1
and microwave conditions were monitored by H NMR analysis, the
microwave-assisted reaction being conducted in a domestic microwave
oven. The % distribution of reactants and product 4c were determined at
intervals and, from the plots of the resulting data (illustrated in Fig. 2), it is
apparent that both processes involve formation of an intermediate mono-
[
10]
amide 3 (R ¼ 2-MeOC H ; Sch. 1), but that the microwave-assisted reac-
6
4
tion is dramatically faster than the thermal reaction. In fact, for similar
conversion levels, the microwave-assisted process required only 5 min
compared to 48 h for the thermal reaction! In order to determine the effect
of sample size, the microwave-assisted reaction was repeated using 2.5- and
5-fold increases in the total mass of the reagents, while maintaining the mass
ratio 1a : 2c at 1 : 1.6. In each case, the product 4c was obtained in a yield of
8
4 Æ 2% after 5 min, indicating that, within the limits investigated, the sample
size does not adversely affect conversion efficiency. The protocol (Method D)
was successfully extended to the synthesis of the malonamide derivatives 4b
and 4d–f, ligand 4e being isolated in 96% yield when the reaction mixture was
irradiated for 6 min (Table 1). The allyl derivative 4f, obtained in 54% yield
after irradiation for 7.5 min, has the potential for incorporation in a silver(I)-
selective molecularly imprinted polymer (MIP).
The malonamide ligands 4a–f (of which only compound 4c appears to
[
11]
have been reported previously ) were fully characterised using elemental
1
high-resolution MS) and spectroscopic (IR and H and C NMR) analysis.
13
(
In the case of the o-anisidine derivative 4c, crystals were obtained which
were suitable for X-ray analysis, and the crystal structure of this compound
is illustrated in Fig. 3.
Metal extraction studies were conducted following a reported
[12]
protocol, using ethyl acetate as the organic solvent. Residual silver in the

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DESIGNER LIGANDS. VIII
3211
Figure 3. X-ray crystal structure of the malonamide ligand 4c, showing the
crystallographic numbering.
Figure 4. ICP-MS data showing metal extraction efficiencies for ligand 4b.
aqueous layer was initially determined by Atomic Absorption (AA) analysis
and the results confirmed that:- (i) equilibration was achieved in less than
15 min; and (ii) ligand 4b exhibited high extraction efficiency over a wide pH
range (2.70–9.0). Metal selectivity was determined by ICP-MS analysis of
the residual silver, copper and lead in the aqueous phases following solvent
extraction using each of the ligands 4b–4e. Traces of ethyl acetate in the
aqueous solutions were found to affect the ICP-MS results adversely and,
consequently, the aqueous aliquots were heated to boil off residual organic
solvent and then diluted back to the original volume prior to analysis. The
ICP-MS results indicate that, while all four of the ligands examined exhibit
0
some selectivity for silver(I) over copper(II) and lead(II), N,N -bis(2-benzyl-
sulfanylethyl)malonamide 4b extracts silver with remarkably high selectivity
and excellent efficiency (97%; see Fig. 4).
In conclusion, it is apparent that the application of microwave
irradiation has permitted the rapid, convenient and efficient synthesis of

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3
212
DAUBINET AND KAYE
a range of malonamide derivatives, some of which exhibit potential as
silver(I)-selective ligands.
EXPERIMENTAL
NMR spectra were recorded for CDCl3 solutions on a Bruker
AVANCE 400 MHz NMR spectrometer and referenced using the solvent
signals (ꢀH 7.25 and ꢀC 77.0 ppm). Low-resolution mass spectra were
obtained on a Finnigan MATGCQ mass spectrometer and high-resolution
analyses on a Kratos MS 80RF mass spectrometer (Cape Technikon Mass
Spectrometry Unit). Infrared spectra were recorded on a Perkin-Elmer
Spectrum 2000 spectrophotometer. Microwave-assisted reactions were
conducted in an unmodified DEFY 1000 W domestic microwave oven, oper-
ating at 2.45 GHz, with five ‘‘power-level’’ settings; the reagents were placed
in a 25 mL conical flask fitted with a condenser-vent. Diethyl allylmalonate
[13]
1b
was prepared by standard alkylation of diethyl malonate. The AA
data were acquired on a GBC 909AA spectrophotometer using an air–
acetylene flame, and the ICP-MS data were obtained by the Metal
Separations Group at the University of Port Elizabeth.
0
N,N -Bis(2-methoxyethyl)malonamide 4a: Method C. A solution of
diethyl malonate 1a (1.0 g, 6.2 mmol) and 2-methoxyethylamine 2a (0.98 g,
13.0 mmol) in MeOH was heated under reflux for 16 h. The solvent was then
removed in vacuo, and the crude product was recrystallised from EtOAc-
0
hexane to yield, as colourless needles, N,N -bis(2-methoxyethyl)malonamide
ꢀ
þ
4
a (0.84 g, 62%), m.p. 93–94 C (EtOAc-hexane) (Found: M , 218.1258.
ꢁ
1
(KBr)/cm 3280 (NH) and 1667
C H N O requires M, 218.1267); ꢁ
max
9
18
2
4
(
(
(
(
CO); ꢀ (400 MHz; CDCl ) 3.16 (2H, s, CH CO), 3.33 (6H, s, CH O), 3.42
H 3 2 3
8H, m, OCH CH NH) and 7.17 (2H, s, NH); ꢀ (100 MHz; CDCl ) 39.3
2
2
C
3
CH CH NH), 43.0 (CH CO), 58.7 (CH O), 70.8 (CH CH O) and 167.3
2
2
2
2
3
2
þ
CO); m/z (EI) 219 (M , 10%) and 112 (100).
Method A. A solution of diethyl malonate 1a (2.1 g, 13 mmol) and
-methoxyethylamine 2a (2.0 g, 27 mmol) in hexane (10 mL) was stirred
2
for 7 days at r.t. The solvent was then removed in vacuo, and the crude
product recrystallised from EtOAc-hexane to yield, as colourless needles,
0
N,N -bis(2-methoxyethyl)malonamide 4a (0.67 g, 24%).
0
N,N -Bis(2-benzylsulfanylethyl)malonamide 4b: Method D. A mixture of
diethyl malonate 1a (1.60 g, 10.0 mmol) and S-benzylcysteamine 2b (3.34 g,
2
0.0 mmol; obtained by the reaction of S-benzylcysteamine hydrochloride
with 0.1 M methanolic NaOMe) was exposed to microwave irradiation
defrost setting) for 3.5 min. The mixture was allowed to cool, the resulting
precipitate filtered off, washed with Et O and then recrystallised from EtOH
(
2

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DESIGNER LIGANDS. VIII
3213
0
to yield, as yellow crystals, N,N -bis(2-benzylsulfanylethyl)malonamide 4b
ꢀ
þ
(
2.21 g, 55%), m.p. 105–106 C (from EtOH) (Found: M , 402.1442.
C H N O S requires 402.1436); ꢁ
max
CO); ꢁmax (CaF )/cm 3374 (NH) and 1678 (CO); ꢀH (400 MHz; CDCl3)
2
ꢁ1
(KBr)/cm 3300 (NH) and 1630
2
1
26
2
2
2
ꢁ1
(
2.53 (4H, t, CH CH S), 3.10 (2H, s, COCH ), 3.38 (4H, m, NHCH ), 3.70
2 2 2 2
(
(
(
(
4H, s, PhCH S), 7.18 (2H, br s, NH) and 7.21–7.30 (10H, m, ArH); ꢀ
2
C
100 MHz; CDCl ) 30.8 (CH CH S), 35.9 (PhCH S), 38.4 (COCH ), 43.0
2
3
2
2
2
CH CH NH), 127.2, 128.6, 128.8 and 138.0 (ArC) and 167.2 (CO); m/z
2
2
þ
EI) 402 (M , 1%) and 311 (100).
Method A. A solution of diethyl malonate 1a (0.40 g, 2.5 mmol) and
S-benzylcysteamine hydrochloride (0.991 g, 4.9 mmol) in methanolic
NaOMe (0.1 M, 50 mL) was stirred for 7 days. The solvent was then
removed in vacuo, and the crude product recrystallised from EtOAc-
0
hexane to yield, as a fine yellow powder, N,N -bis(2-benzylsulfanylethyl)-
malonamide 4b (0.24 g, 24%).
0
N,N -Bis(2-methoxyphenyl)malonamide 4c: Method D. A mixture of
diethyl malonate 1a (1.02 g, 6.4 mmol) and o-anisidine 2c (1.63 g,
1
5
3.2 mmol) was subjected to microwave irradiation (defrost setting) for
1
min. H NMR analysis of the crude product (1.76 g) revealed that 81%
of the diethyl malonate 1a had been converted to the desired product. The
crude mixture was recrystallised from EtOAc-hexane to yield, as colourless
0
needles, N,N -bis(2-methoxyphenyl)malonamide 4c (1.13 g, 65%), m.p.
ꢀ
[11]
ꢀ
1
63–165 C (from EtOH-hexane) (lit.,
þ
163–168 C; from EtOH) (Found:
ꢁ1
M , 314.1256. C H N O requires M, 314.1267); ꢁ
(KBr)/cm 3369
1
7
18
2
4
max
(
(
NH) and 1676 (CO); ꢀH (400 MHz; CDCl ) 3.55 (2H, s, CH CO), 3.89
3 2
6H, s, CH O), 6.88 (2H, d, ArH), 6.95 (2H, t, ArH), 7.04 (2H, t, ArH),
3
8
.33 (2H, d, ArH) and 8.96 (2H, br s, NH); ꢀC (100 MHz; CDCl ) 45.8
3
(
and 164.8 (CO); m/z (EI) 314 (M , 100%).
CH CO), 55.8 (CH O), 110.1, 120.3, 120.9, 124.3, 127.2 and 148.4 (ArC)
2 3
þ
Method B. A solution of malonyl dichloride (0.5 mL, 4 mmol) in
anhyd. THF (100 mL) was added dropwise, over 3.5 h, to a solution of
o-anisidine 2c (1.02 g, 8.3 mmol) and pyridine (0.7 mL) in dry THF
(200 mL), under dry nitrogen. The reaction mixture was stirred overnight;
water (20 mL) was then added and the resulting mixture extracted with
EtOAc (3 ꢂ 50 mL). The EtOAc extracts were dried over anhyd. MgSO ,
4
and the solvent was removed in vacuo to yield the crude product (1.51 g). A
solution of the crude product in EtOH was filtered through a silica plug and
0
dropwise addition of Et O to the filtrate gave, as colourless needles, N,N -
2
bis(2-methoxyphenyl)malonamide 4c (0.29 g, 23%).
Method C. A mixture of diethyl malonate 1a (1.0 g, 6.2 mmol) and
o-anisidine 2c (1.6 g, 13 mmol) was heated under reflux for 48 h. Volatile
material was removed in vacuo, and the residue was dissolved in EtOAc

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214
DAUBINET AND KAYE
(
1 mL) and hexane (5 mL) was added slowly. The resulting precipitate was
filtered off and washed with hexane until the organic phase remained colour-
less. The residue was then dried to yield, as a fine, light-brown powder,
0
N,N -bis(2-methoxyphenyl)malonamide 4c (1.3 g, 66%), which was shown
by TLC and NMR analysis to be pure.
0
N,N -Bis(2-methylsulfanylphenyl)malonamide 4d: Method D. A mixture
of diethyl malonate 1a (1.0 g, 6.2 mmol) and 2-methylsulfanylphenylamine
2
d (1.74 g, 12.5 mmol) was subjected to microwave radiation (defrost setting)
1
for 6 min. H NMR analysis of the crude product (2.22 g) revealed that ca.
2% of the diethyl malonate 1a had been converted to the desired product.
The crude mixture was recrystallised from EtOAc-hexane to yield, as a fine,
6
0
light-yellow crystals, N,N -bis(2-methylsulfanylphenyl)malonamide 4d (1.1 g,
ꢀ
þ
4
9%), m.p. 114–116 C (from EtOAc-hexane) (Found: M , 346.0823
ꢁ
1
(KBr)/cm 3225 (NH), 1682
C H N O S requires M, 346.0810); ꢁ
max
1
7
18
2
2
2
and 1673 (CO); ꢀH (400 MHz; CDCl ) 2.39 (6H, s, CH S), 3.63 (2H, s,
3
3
CH CO), 7.09 (2H, t, ArH), 7.27 (2H, t, ArH), 7.46 (2H, d, ArH), 8.26
2
(
2H, d, ArH) and 9.33 (2H, br s, NH); ꢀC (100 MHz; CDCl ) 18.6
3
(
and 165.0 (CO); m/z (EI) 346 (M , 85%) and 299 (100).
CH S), 45.6 (CH CO), 121.3, 125.0, 126.7, 128.4, 132.2 and 137.4 (ArC)
þ
3
2
Method C. The experimental procedure described for the synthesis of
N,N -bis(2-methoxyphenyl)-malonamide 4c (Method C) was followed, using
diethyl malonate 1a (1.0 g, 6.2 mmol) and 2-methylsulfanylphenylamine 2d
0
(
product was then dissolved in of CHCl (1 mL) and hexane (5 mL) was added
1.74 g, 12.5 mmol). Volatile material was removed in vacuo, and the crude
3
slowly. The resulting mixture was filtered and the residual solid washed with
hexane until the organic phase was colourless. The product was dried to yield,
0
as a fine, light-yellow powder, N,N -bis(2-methylsulfanylphenyl)malonamide
4d (0.64 g, 30%), which was shown by TLC and NMR analysis to be pure.
0
N,N -Bis(2-methoxybenzyl)malonamide 4e: Method D. A mixture of
diethyl malonate 1a (1.0 g, 6.2 mmol) and 2-methoxybenzylamine 2e
1.74 g, 12.5 mmol) was exposed to microwave radiation (defrost setting)
(
for 3.5 min. NMR analysis of the crude product (2.15 g) revealed that
the sample contained only the desired product. The crude mixture was
recrystallised from EtOAc-hexane to yield, as fine, white crystals,
0
ꢀ
N,N -bis(2-methoxybenzyl)malonamide 4e (2.04 g, 96%), m.p. 120–122 C
þ
(
from EtOAc-hexane) (Found: M , 342.1586. C H N O requires M,
4
42.1580); ꢁmax (KBr)/cm 3297 (NH) and 1655 (CO); ꢀH (400 MHz;
CDCl ) 3.14 (2H, s, CH CO), 3.82 (6H, s, CH O), 4.41 (4H, d,
1
9
22
2
ꢁ
1
3
3
2
3
ArCH NH), 6.86 (4H, m, ArH), 7.22 (4H, m, ArH) and 7.41 (2H, br s,
2
NH); ꢀC (100 MHz; CDCl ) 39.2 (ArCH ), 43.2 (CH CO), 55.2 (CH O),
3
2
2
3
1
10.3, 120.5, 125.9, 128.7, 129.3 and 157.4 (ArC) and 167.0 (CO); m/z
þ
(
EI) 342 (M , 40%) and 136 (100).

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DESIGNER LIGANDS. VIII
3215
0
2
-Allyl-N,N -bis(2-methoxyphenyl)-1,3-propanediamide 4f: Method D.
[
13]
A mixture of diethyl allylmalonate 1b (2.0 g, 10 mmol) and o-anisidine 2c
2.47 g, 20.0 mmol) was subjected to microwave irradiation (defrost setting)
for 7.5 min. The mixture was allowed to cool, and the resulting precipitate
(
filtered off, washed with Et O and then recrystallised from EtOH to yield, as
2
0
colourless crystals, 2-allyl-N,N -bis(2-methoxyphenyl)-1,3-propanediamide 4f
þ
ꢀ
(
1.91 g, 54%), m.p. 144–146 C (from EtOH) (Found: M , 354.1585.
ꢁ
1
(KBr)/cm 3371 (NH) and 1677
C H N O requires M, 354.1580); ꢁ
max
2
0
22
2
4
(
CO); ꢀ (400 MHz; CDCl ) 2.84 (2H, t, CH CHCO), 3.37 (1H, t, CHCO),
H 3 2
3
.89 (6H, s, CH O), 5.10 and 5.21 (2H, 2xd, CH ¼CH), 5.88 (1H, m,
3
2
CH ¼CH), 6.87 (2H, d, ArH), 6.95 (2H, t, ArH), 7.05 (2H, t, ArH), 8.34
2
(
2H, d, ArH) and 8.79 (2H, br s, NH); ꢀ (100 MHz; CDCl ) 36.6 (CH CH),
C 3 2
5
1
5.8 (CH O), 57.5 (CHCO), 110.1 (ArC), 118.3 (CH ¼CH), 120.1, 120.9,
3
2
24.3 and 127.2 (ArC), 133.7 (CH ¼CH), 148.4 (ArC) and 167.7 (CO); m/z
2
þ
(
EI) 354 (M , 79%) and 205 (100).
X-ray crystal data for 4c: Monoclinic, space group P2 (1)/n; a ¼ 8.5670
ꢀ
ꢁ3
˚
(
1), b ¼ 15.3299 (3), c ¼ 23.516 (1) A, ꢂ ¼ 90; ꢃ ¼ 99.116 (1); g ¼ 90 ,
3
A ,
˚
V ¼ 3049.4
(2)
Z ¼ 4,
F(000) ¼ 1328,
D ¼ 1.369 g cm
,
c
ꢁ
1
ꢄ ¼ 0.099 mm . Data collection with graphite-monochromated Mo-K
a
ꢀ
˚
radiation, ꢅ ¼ 0.71073 A, T ¼ 173(2) K, ꢆ range 2.20–25.35 , 15787 reflections
collected(ꢁ10 ꢃ h ꢃ 6,ꢁ18 ꢃ k ꢃ 18, ꢁ18 ꢃ l ꢃ 28), 5458uniquewithI>2s(I ).
Hydrogen atoms were placed in calculated positions and the structure was
[
14]
solved by direct methods using SHELX-93;
full-matrix least-squares
refinement converged at R ¼ 0.0424, wR ¼ 0.0850, GOF ¼ 1.056.
1
2
Crystallographic data for the structure in this paper have been deposited
with the Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC 163237. Copies of the data can be obtained, free of
charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK,
(
Fax: þ44 1223 336033 or E-mail: deposit@ccdc.cam.ac.uk).
Metal Extraction Studies: The malonamide ligands 4b–e were dis-
ꢁ
2
solved in EtOAc to yield concentrations of ca. 1.8 ꢂ 10 ; the aqueous
ꢁ
2
phase contained 10 ppm Ag in a 2.5 ꢂ 10 M NaNO solution adjusted
3
to pH 2.78 with HNO . The heterogeneous mixtures were stirred vigorously
3
ꢀ
for 15 min (a period shown to permit equilibration) at 25 C, using a 150 mL
[
jacketed beaker and following Sole’s methodology.
12]
For AA analysis,
calibration curves were determined for each data set, and the aqueous
samples were analysed undiluted. For ICP-MS analysis, the aqueous
phase contained 10 ppm of each of the metals, silver, lead and copper.
Aliquots (25 mL) of the aqueous phases, obtained following extraction,
were concentrated on a steam bath for 0.5 h, after which the samples were
diluted back to 25 mL. All standards and samples were diluted 20-fold for
the ICP-MS analysis, and two isotopes of each metal were used in the

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3
216
DAUBINET AND KAYE
6
3
65
107
109
206
208
analysis, i.e. Cu and Cu; Ag and Ag; and Pb and Pb, each ICP-
MS result representing the average of 6 successive readings. The average
extraction efficiencies (Cu; Ag; Pb%) as determined by ICP-MS analysis
were as follows:- 4b (9; 97; 8%); 4c (6; 12; 5%); 4d (7; 27; 7%); and 4e
(
10; 25; 8%).
ACKNOWLEDGMENTS
The authors thank MINTEK, Rhodes University and the National
Research Foundation (NRF) for generous financial support, Dr. John
Bacsa (University of Cape Town) for the X-ray structure determination,
Ms. Paula Antunes for assistance with the AA analyses and Dr. Eric
Hosten (University of Port Elizabeth) for the ICP-MS analyses.
REFERENCES
1. Part 7. Kaye, P.T.; Wellington, K.W. Synth. Commun., 2001, 31(16),
2405–2111.
2. Hagemann, J.P.; Kaye, P.T. Tetrahedron 1998, 55, 869–874.
3. Hagemann, J.P.; Kaye, P.T. J. Chem. Soc., Perkin Trans. 1 1999,
341–347.
4
5
. Hagemann, J.P.; Kaye, P.T. Synth. Commun. 1997, 27, 2539–2546.
. Iveson, P.B.; Drew, M.G.B.; Hudson, M.J.; Madic, C. J. Chem. Soc.,
Dalton Trans. 1999, 3605–3610.
6
7
. Daubinet, A. Ph.D. Thesis. Rhodes University, 2001.
. Ramalingam, K.; Raju, N.; Nanjappan, P.; Linder, K.E.; Pirro, J.;
Zeng, W.; Rumsey, W.; Nowotnik, D.P.; Nunn, A.D. J. Med. Chem.
1994, 37, 4155–4163.
8
9
. Kingston, H.M.; Haswell, S.J. Microwave-Enhanced Chemistry:
Fundamentals, Sample Preparation, and Applications; American
Chemical Society: Washington, DC, 1997; p. 1ff.
. Goncalo, P.; Roussel, C.; Melot, J.M.; Vebrel, J. J. Chem. Soc., Perkin
´ ´
Trans. 2 1999, 2111–2115.
1
0. With the Exception of Compound 3c, the Intermediate Monoamides 3
were not Isolated. Analytical Data for Compound 3c are as Follows:-
ꢀH(400 MHz; CDCl ) 1.29 (3H, t,CH CH ), 3.47 (2H, s, CH CO), 3.89
3
3
2
2
(3H, s, CH O), 4.23 (2H, q, CH CH ), 6.87 (1H, d, Ar–H), 6.94 0(1H,
3 3 2
t, Ar-H), 7.03 (1H, t, Ar-H), 8.33 (1H, d, Ar-H) and 9.35 (1H, s, NH);
ꢀC(100 MHz; CDCl ) 14.0 (CH CH ), 42.6 (CH CH ), 55.8 (CH O),
3
3
2
3
2
3

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2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
DESIGNER LIGANDS. VIII
3217
61.7 (CH CO), 110.1,120.2, 121.0, 124.0, 127.4 and 148.3 (Ar-C), 162.7
2
and 169.1 (2 ꢂ CO).
1
1. Nishino, H.; Ishida, K.; Hashimoto, H.; Kurosawa, K. Synthesis 1996,
888–896.
12. Sole, K.C.; Hiskey, B. Hydrometallurgy 1992, 30, 345–365.
13. Beilstein’s ‘‘Handbuch der Organischen Chemie’’: H 2, 776.
14. Sheldrick, G.M. SHELX97. Programme for Crystal Structure Solution;
¨
University of Gottingen: Germany, 1997.
Received in the USA October 15, 2001

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©
2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.