Synthesis and characterization of new mono-, bis-, and tris-oxamato proligands

Article abstract of DOI:10.1016/j.tetlet.2010.07.117

This communication presents the synthesis and the characterization of new organic molecules bearing up to three N-phenyl-oxalamic acid ethyl esters. The syntheses are based on Sonogashira-type cross-coupling reactions with preformed oxalamic ester interme

Full text of DOI:10.1016/j.tetlet.2010.07.117

Tetrahedron Letters 51 (2010) 5157–5159
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Tetrahedron Letters
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Synthesis and characterization of new mono-, bis-, and tris-oxamato proligands
*
Christophe Stroh , Alexandrina Stuparu
Karlsruher Institut für Technologie (KIT), Institut für Nanotechnologie, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
This communication presents the synthesis and the characterization of new organic molecules bearing
up to three N-phenyl-oxalamic acid ethyl esters. The syntheses are based on Sonogashira-type
cross-coupling reactions with preformed oxalamic ester intermediate building blocks. The short syn-
thetic pathways lead easily to valuable potential oxamato-bridging ligands with overall interesting
yields.
Received 27 April 2010
Revised 20 July 2010
Accepted 21 July 2010
Available online 25 July 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Proligand
Polytopic
Oxamato
Sonogashira cross-coupling
During the last decades, a growing interest for polymeric coor-
dination networks motivated the scientific community. Applica-
tions of three-dimensional metal-organic frameworks (MOFs) are
numerous. For example, gas storage materials1 or molecule-based
magnets2 have been reported. Coordination polymers of lower
dimentionality are also of interest.3 The controlled design of new
scaffolds is the focus of many research.4
sional scaffolds with magnetic properties, like the easy synthesis
and the good solubility of the corresponding precursor.10
Herein, we report the synthesis and characterization of new
organic building blocks containing up to three N-phenyl-oxalamic
acid ethyl ester groups (Fig. 1). Such ethyl esters of oxalamic acids
can be used in situ for the preparation of oxamato-bridged metal
complexes.
Up to now, thousands of coordination polymers have been
reported. Nevertheless, the design and synthesis of new bridging
organic molecules remain a challenging task for the improvement
of the final materials. Various ditopic ligands have been prepared.
Their coordination chemistry has been well documented in the lit-
erature.5 Stepwise introduction of different metals, a so called
‘complex as ligand’ or ‘expanded ligand’ approach, is probably a
key step for the construction of heterometallic scaffolds.6 This
opportunity is interesting for magnetic properties regarding the
ability of ligands to propagate spin alignment.7
We present in this communication the use of iodo- and ethynyl-
functionalized phenyl-oxalamic esters as reactants in a Sonogash-
ira-type cross-coupling reaction. This enables the direct synthesis
Magnetic exchange interactions can be strong with ligands
having one or two bridging atoms, as shown for example in cya-
no-bridged frameworks.8 However, the structural variety is rather
limited. A much larger diversity is offered by conjugated systems
having three or more bridging atoms. This higher modulation is
profitable for structure–property correlations.9 Furthermore, addi-
tional variations allow the design of unique polydentate/polytopic
ligands. Among several interesting diamagnetic-bridging ligands,
the oxamato group attracted our attention. As reported in the liter-
ature, it combines several advantages for building multidimen-
* Corresponding author. Tel.: +49 7247 82 8173; fax: +49 7247 82 6368.
E-mail address: christophe.stroh@kit.edu (C. Stroh).
Figure 1. Drawing of the target mono-, bis- and tris-ditopic proligands.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.07.117

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C. Stroh, A. Stuparu / Tetrahedron Letters 51 (2010) 5157–5159
Scheme 2. General reaction scheme for the introduction of an oxamate functional
group.
A careful purification by column chromatography on SiO2 affor-
Scheme 1. Synthesis of the mono oxalamic acid ethyl ester 1.
ded this pincer-type proligand. N-(3-{2-[3-(ethoxyoxalyl-amino)-
phenylethynyl]-phenylethynyl}-phenyl)-oxalamic acid ethyl ester
2 has been characterized by 1H NMR, 13C NMR, and IR spectrosco-
pies, mass spectrometry, and elemental analysis.
of the target molecule without the handling of amine intermedi-
ates, and/or additional protection–deprotection steps often re-
quired for the synthesis of larger molecules.
A Sonogashira-type cross-coupling reaction between an excess
of the ethynyl compound 9 and butoxy-2,4,6-triiodobenzene 1118
allowed the synthesis of N-(4-{4-butoxy-3,5-bis-[4-(ethoxyoxal-
yl-amino)-phenylethynyl]-phenylethynyl}-phenyl)-oxalamic acid
ethyl ester 3. The good solubility of the compound provided by
the butoxyl group allowed purification by column chromatogra-
phy. While the 1H NMR spectrum is easily analyzed, the 13C NMR
is more complex due to the butoxyl fragment, and the C2 symme-
try along the 1,4-carbon atoms of the central phenyl ring. As a con-
sequence of the presence of this butoxyl fragment, two sets of
ethynyl-phenyl-oxalamic esters are distinguished. For instance,
four signals ranging between 85.0 and 93.7 ppm are attributed to
the 2 equiv ethynyl fragments in ortho-position of the butoxyl
and to the non-equivalent para-ethynyl fragment. The aromatic
rings and the splittings of some signals are in keeping with the
structure. Two carbonyl signals of the amide groups are clearly
observed but only a broad peak for the ester carbon atoms is seen.
This can be reasonably attributed to the overlapping of two close
signals. Our interpretation is supported by the 1H NMR spectrum,
where the chemical shifts for the two non-equivalent amide
protons are different for the same reason. The identity of the mol-
ecule is further confirmed by mass spectrometry and its purity by
elemental analysis.
In a first step, we focused on the target compound N-(4-phenyl-
ethynyl-phenyl)-oxalamic acid ethyl ester 1. The synthesis of the
N-(4-iodo-phenyl)-oxalamic acid ethyl ester intermediate 5 in
88% yield was adapted from the literature (Scheme 1).11 This
iodo-derivative has already been synthesized in a different way,
but no full characterization has been reported.12 The second step
could be performed in standard conditions using PdCl2(PPh3)2 cat-
alyst and CuI as co-catalyst. The compound 1 could be obtained in
76% yield after column chromatography.13
To prepare the bis- and tris-functionalized ligands 214 and 315
,
we used the intermediate building blocks bearing terminal triple
bonds. In a first step, we synthesized the ethynyl-building blocks
bearing an oxalamic ester group in meta-position (7) or para-posi-
tion (9) in a standard way (Scheme 2). This reaction has been done
in THF/NEt3 at 50 °C or rt using the corresponding commercially
available ethynyl–aniline derivatives 6 and 8.16
The ammonium salt has been removed by filtration before the
purification of the desired products by column chromatography
on SiO2. The 1H and 13C NMR spectra are in agreement with the
connected amide and ester functional groups of the oxalamic ester
for both compounds 7 and 9. The IR spectra also show the presence
of two bands attributed to the two different C@O bonds of such a
motif.17 Interestingly, the yields for the preparation of these pre-
cursors 7 and 9 are high (97% and 93%, respectively).
In conclusion, using a standard Sonogashira-type cross-cou-
pling reaction, we could easily synthesize various scaffolds with
up to three oxalamic ester groups as potential proligands. While
the yields for the final steps are moderate, the short synthetic path-
ways to get the desired ligand precursors are attractive. The syn-
thesis of poly-functionalized organic scaffolds is now under way.
In a second step, a Sonogashira-type cross-coupling reaction be-
tween 2 equiv of the ethynyl compound 7 and 1,2-diiodobenzene 10
afforded the bis-N-phenyl-oxalamic acid ethyl ester 2 (Scheme 3).
Scheme 3. Synthesis of compounds 2 and 3.

C. Stroh, A. Stuparu / Tetrahedron Letters 51 (2010) 5157–5159
5159
selected IR (KBr pellet, cmÀ1): 3339, 1729, 1703, 1582, 1527, 1472, 1443, 1367,
1292, 1240, 1170, 1111, 1024, 1017, 843, 832, 760, 755, 687, 519; positive ion
ESI (%), MeCN: m/z = 316.12 (100) [M+Na]+, 609.25 (20) [2M+Na]+; Anal. Calcd
for C18H15NO3 (Mr = 293.32): C, 73.71; H, 5.15; N, 4.78. Found: C, 73.58; H,
5.12; N, 4.76.
Acknowledgments
We thank Matthias Fischer for elemental analysis. We thank the
INT and the KIT campus North for the financial support. We thank
Professor Marcel Mayor for the support.
14. Compound 2: 1,2-Diiodobenzene (375 mg, 0.669 mmol) and compound
7
(741 mg, 3.41 mmol) were dissolved in THF/NEt3 (30 mL, 1:1). Pd(PPh3)2Cl2
(80.0 mg, 0.114 mmol) and CuI (22.0 mg, 0.114 mmol) were added under N2.
After stirring overnight at rt, the solvents were removed. The residue was
purified by chromatography (SiO2, hexane/CH2Cl2 1:1–0:1 followed by SiO2,
CH2Cl2/MeCN 9:1) to afford the pure product 2 (339 mg, 59%) as a white
powder.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.07.117.
Rf (SiO2, CH2Cl2/MeCN 94:6): 0.61; mp 178 °C; 1H NMR (CD2Cl2):
d
(ppm) = 1.37 (t, J = 7.2 Hz, 6H), 4.33 (q, J = 7.2 Hz, 4H), 7.35–7.43 (m, 6H),
7.56–7.64 (m, 4H), 8.00 (s, 2H), 9.13 (s, 2H); 13C NMR (CD2Cl2): d (ppm) = 14.0,
63.6, 88.6, 92.9, 120.5, 123.2, 124.1, 125.5, 128.5, 128.7, 129.4, 132.0, 136.9,
154.6, 160.7; 13C-DEPT135 NMR (CD2Cl2): d (ppm) = 13.7, 63.6, 120.4, 123.1,
128.4, 128.6, 129.3, 132.0; selected IR (KBr pellet, cmÀ1): 3334, 2205, 1703,
1604, 1587, 1545, 1478, 1443, 1428, 1368, 1300, 1280, 1265, 1217, 1181, 1166,
1019, 786, 769, 703, 686; positive ion ESI (%), MeCN: m/z = 531.1 (100)
References and notes
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[M+Na]+, 547.1 (30) [M+K]+; UV–vis (MeCN) k, nm ( , MÀ1 cmÀ1): 335 sh
e
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for C30H24N2O6 (Mr = 508.52): C, 70.86; H, 4.76; N, 5.51. Found: C, 70.74; H,
4.82; N, 5.48.
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15. Compound 3: Butoxy-2,4,6-triiodobenzene 11 (353 mg, 0.669 mmol), and
compound 9 (581 mg, 2.67 mmol) were dissolved in dry THF/NEt3 (30 mL,
1:1). Pd(PPh3)2Cl2 (70.5 mg, 0.10 mmol) and CuI (19.0 mg, 0.10 mmol) were
added under N2. After stirring for 5 h at rt, the solvents were removed and the
residue was purified by chromatography (SiO2, hexane/AcOEt 1:1 followed by
SiO2, hexane/CH2Cl2 2:1). The pure product 1 (70 mg, 13%) was obtained as a
white powder.
5. Kharisoc, B. I.; Elizondo Martínez, P.; Jiménez-Pérez, V. M.; Kharissova, O. V.;
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Rf (SiO2, CH2Cl2/AcOEt 1:1): 0.40; mp 91 °C dec; 1H NMR (CD2Cl2):
d
(ppm) = 0.97 (t, J = 7.2 Hz, 3H), 1.39 (t, J = 7.2 Hz, 9H), 1.57–1.65 (m, 2H),
1.84–1.89 (m, 2H), 4.34–4.41 (m, 8H), 7.50–7.56 (m, 6H), 7.61 (s, 2H), 7.63–
7.69 (m, 6H), 8.99–9.00 (m, 3H); 13C NMR (CD2Cl2): d (ppm) = 13.8, 13.8, 19.5,
32.6, 63.9, 74.5, 85.0, 87.7, 89.7, 93.7, 118.1, 118.6, 119.7, 119.7, 119.8, 119.8,
132.5, 132.5, 136.3, 136.7, 136.9, 154.0, 154.0, 160.7, 161.0; 13C-DEPT135 NMR
(CD2Cl2): d (ppm) = 13.7, 13.8, 19.4, 32.6, 63.8, 74.4, 119.6, 119.7, 132.4, 132.5,
136.3; selected IR (KBr pellet, cmÀ1): 3337, 2959, 2935, 2210, 1708, 1605,
1584, 1526, 1471, 1444, 1407, 1370, 1294, 1237, 1179, 1157, 1111, 1015, 837,
525; positive ion ESI (%), MeCN: m/z = 818.2 (100) [M+Na]+, 818.7 (33)
11. Pardo, E.; Carrasco, R.; Ruiz-Garcia, R.; Julve, M.; Lloret, F.; Muñoz, M. C.;
Jouraux, Y.; Ruiz, E.; Cano, J. J. Am. Chem. Soc. 2008, 130, 576.
12. Chattaway, F. D.; Constable, A. B. J. Am. Chem. Soc. 1914, 124.
13. Compound 1: Phenylacetylene (200 mg, 1.77 mmol) and compound 5 (378 mg,
1.18 mmol) were added to dry THF/NEt3 (20 mL, 3:1) under Ar. Pd(PPh3)2Cl2
(42 mg, 0.060 mmol) and CuI (11 mg, 0.060 mmol) were added, and the
mixture was stirred at rt overnight. The solvents were evaporated, and the
crude was purified by column chromatography (CH2Cl2/hexane 9:1–1:0) to
give 265 mg of the desired compound 1 (76%).
[2M+2Na]2+
(MeCN) k, nm (
46H41N3O10 (Mr = 795.83): C, 69.42; H, 5.19; N, 5.28. Found: C, 69.23; H, 5.06;
;
1216.4 (60) [3M+2Na]2+
e
; ; UV–vis
1614.6 (20) [4M+2Na]2+
, MÀ1 cmÀ1): 321 (114,000), 221 (39,660); Anal. Calcd for
C
N, 5.25.
16. (a) Winkelmann, O.; Linder, D.; Lacour, J.; Näther, C.; Lüning, U. Eur. J. Org.
Chem. 2007, 3687; (b) Waltman, A. W.; Grubbs, R. H. Organometallics 2004, 23,
3105; (c) Cervera, B.; Sanz, J. L.; Ibáñez, M. J.; Vila, G.; Lloret, F.; Julve, M.; Ruiz,
R.; Ottenwaelder, X.; Aukauloo, A.; Poussereau, S.; Journaux, Y.; Muñoz, M. C. J.
Chem. Soc., Dalton Trans. 1998, 781.
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Cervera, B.; Muñoz, M. C. Eur. J. Inorg. Chem. 1999, 209.
18. Drew, R. D.; Sturtevant, J. M. J. Am. Chem. Soc. 1939, 61, 2666.
Rf (SiO2, CH2Cl2/hexane 1:2): 0.46; 1H NMR (CDCl3):
d (ppm) = 1.43 (t,
J = 7.2 Hz, 3H), 4.42 (q, J = 7.2 Hz, 2H), 7.32–7.37 (m, 3H), 7.50–7.56 (m, 4H),
7.63–7.66 (m, 2H), 8.94 (s, 1H); 13C NMR (CDCl3): d (ppm) = 14.1, 64.0, 88.9,
89.9, 119.7, 120.5, 123.3, 128.5, 128.5, 131.7, 132.7, 136.3, 153.9, 161.0; 13C-
DEPT135 NMR (CDCl3): d (ppm) = 14.0, 63.9, 119.6, 128.3, 128.4, 131.6, 132.6;