Synthesis of a (thienylethenyl)benzimidazole platinum acetylide complex

Article abstract of DOI:10.1016/j.tetlet.2012.01.023

A new platinum acetylide complex based on 6-dialkylaminobenzimidazol-2-yl- vinyl-2-thiophene-5-ylethyne was synthesized in seven steps and 2% overall yield.

Full text of DOI:10.1016/j.tetlet.2012.01.023

Tetrahedron Letters 53 (2012) 1564–1566
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Tetrahedron Letters
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Synthesis of a (thienylethenyl)benzimidazole platinum acetylide complex
⇑
Matthew C. Davis , Lawrence C. Baldwin, Thomas J. Groshens
Chemistry & Materials Division, Michelson Laboratory, Naval Air Warfare Center, China Lake, CA 93555, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
A new platinum acetylide complex based on 6-dialkylaminobenzimidazol-2-yl-vinyl-2-thiophene-5-yle-
thyne was synthesized in seven steps and 2% overall yield.
Published by Elsevier Ltd.
Received 20 December 2011
Revised 3 January 2012
Accepted 5 January 2012
Available online 28 January 2012
Keywords:
Platinum acetylide
Sonogashira
Alkyne
Thiophene
Benzimidazole
Platinum
platinum acetylides) are
r
–acetylide complexes (commonly referred to as
–electron conjugated molecules with
p
platinum(II) bonded to two ethynyl groups typically in the trans
configuration along with two phosphorus, nitrogen, or arsine con-
taining ligands, Figure 1.1 Platinum acetylides have shown interest-
ing photophysical properties such as two-photon absorption and
nonlinear optical effects.2 As part of a project to identify new mate-
rials for optical power limiting devices,3,4 several group VIII metal
acetylides were prepared for evaluation. This Letter will describe
the synthesis of a new platinum acetylide (1), Figure 1.
Starting with 2,4-difluoronitrobenzene, selective nucleophilic
aromatic substitution of the ortho fluorine atom with ethylamine
gave intermediate 2 in good yield, Scheme 1. Substitution of the
second fluorine with 2-(methylamino)ethanol gave diaminonitro-
benzene 3 in excellent yield. To make the overall synthesis more
convergent, acryloyl chloride 7 was prepared in three steps as
shown in Scheme 2. Initial samples of 2-iodothiophene-5-carbox-
aldehyde (8)5 were prepared by the iodination of thiophene-2-car-
boxaldehyde using the procedure of Wu et al.6 This reaction was
capricious to scale-up and later batches of 8 were prepared consis-
tently in good yield by adapting the iodination conditions of Barri-
os Sosa et al.7 A minor impurity observed by 1H nuclear magnetic
resonance (NMR) in this reaction was thiophene-2-carboxylic acid,
presumably formed by the oxidation of the aldehyde by the peri-
odic/persulfuric acids present. Doebner-modification8 of the Perkin
reaction of aldehyde 8 with malonic acid in hot pyridine gave the
unreported acrylic acid 9. Typically these condensation reactions
are performed at reflux temperature (pyridine boiling point
Figure 1. Generic platinum acetylide complex and structure of new molecule 1
synthesized.
Scheme 1. Reagents and conditions: (a) EtNH3Cl, H2O, TEA; (b) MeNH(CH2)2OH,
K2CO3, N,N-dimethylacetamide; (c) H2, Pd/C, HOAc, THF; (d) 6, TEA, THF; (e)
(HOCH2)2, HOAc, reflux.
⇑
Corresponding author.
E-mail address: matthew.davis@navy.mil (M.C. Davis).
0040-4039/$ - see front matter Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2012.01.023

M. C. Davis et al. / Tetrahedron Letters 53 (2012) 1564–1566
1565
Scheme 2. Reagents and conditions: (a) NaIO4, I2, H2O, CCl4, HOAc, H2SO4; (b)
CH2(CO2H)2, pyridine, piperidine, reflux; (c) SOCl2.
118 °C) however it was found to occur even at 60 °C, although with
significant accumulation of the intermediate ylidenemalonic acid
as observed by 1H NMR spectroscopy. Increasing the temperature
to 75 °C brought the reaction to completion overnight and resulted
in higher quality product. The acrylic acid 9 was converted into
Scheme 3. Reagents and conditions: (a) Me3SiCCH, Pd(OAc)2, PPh3, CuI, DIPA, THF,
reflux; (b) TBAF, THF; (c) CuI, HN(CH(Me)2)2, THF.
acryloyl chloride
7
with thionyl chloride.9–11 Returning to
Scheme 1, it was found that a two-step sequence of reduction fol-
lowed by the amidation of 3 could be combined efficiently. Follow-
ing catalytic hydrogenation of 3, the reaction mixture was
blanketed with nitrogen and triethylamine was added followed
by the addition of acryloyl chloride 7. In this way, the isolation of
air-sensitive 4 was avoided and the yield of amide 5 was markedly
improved. Proton NMR analysis confirmed that the acylation event
occurred at the primary amine due to the amide proton resonance
at 9.17 ppm. Cyclization of 5 in refluxing ethylene glycol contain-
ing 2 equiv of acetic acid gave the benzimidazole 6.12 Single crystal
X-ray analysis of 6 confirmed the desired constitution, Figure 2.13
The synthesis was completed by the sequence shown in
Scheme 3. Sonogashira reaction of 6 with trimethylsilylacetylene
gave the protected acetylene 10.14 The latter was deprotected to
give the terminal acetylene 11 with tetrabutylammonium fluoride
in tetrahydrofuran. The low yield of this deprotection may be due
to the sensitivity of the benzimidazole ring to the basic nature of this
reagent. The cis dichlorobis(tri-n-butylphosphine)platinum(II) (12)
was prepared according to the method of Kauffman and Teter.15 The
value obtained for 1J(195Pt–31P) of 3517 Hz agrees perfectly with the
previously reported value.16,17 Sonogashira reaction of 12 with an
excess of 11 in the presence of diisopropylamine base and catalyzed
Table 1
Comparison of 31P and 195Pt NMR spectroscopy of complex 1 with cis and trans
PtCl2(PnBu3)2 (12) in CDCl3 at 25 °C
Compound
31P (ppm)
JPtP (Hz)
cis 12
trans 12
1
+1.6
+5.1
+4.2
3517
2388
2330
by copper(I) iodide gave the platinum acetylide complex 118 in low
and unoptimized yield to complete the synthesis.19 Combustion
analysis proved that the substance contained only mononuclear
platinum(II) rather than symmetrical dinuclear platinum(I).20
Although the initial platinum species 12 had the cis configura-
tion, the complex 1 appears to be the more thermodynamically fa-
vored trans isomer, a facile isomerization previously reported.21,22
Phosphorus-31 and 13C NMR spectroscopy showed the characteris-
tic values for the chemical shift of phosphorus as well as the cou-
pling of 195Pt–31P signifying trans orientation in 1, Table 1.23–26
Experiments are underway to obtain crystals of 1 suitable for
Figure 2. X-ray crystal structure of compound 6.

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M. C. Davis et al. / Tetrahedron Letters 53 (2012) 1564–1566
7. Barrios Sosa, A. C.; Williamson, R. T.; Conway, R.; Shankar, A.; Sumpter, R.;
Cleary, T. Org. Process Res. Dev. 2011, 15, 449–454.
8. Doebner, O. Ber. Dtsch. Chem. Ges. 1900, 33, 2141–2142.
9. King, W. J.; Nord, F. F. J. Org. Chem. 1949, 14, 405–410.
10. Saur, O.; Hackling, A. E.; Perachon, S.; Schwartz, J. C.; Sokoloff, P.; Stark, H. Arch.
Pharm. Chem. Life Sci. 2007, 340, 178–184.
X-ray structural analysis to provide further evidence for this con-
clusion. In summary, the synthesis of a new platinum acetylide
complex (1) containing a heterocyclic alkyne was completed in se-
ven linear steps and 2% overall yield. Photophysical studies of 1
along with some of its derivatives will be the subject of future
communication.
11. Zhao, D. Y.; Meng, Q. Y.; Cui, X. P.; Yang, H. Chin. Chem. Lett. 2009, 20, 1283–
1286.
12. Dubey, P. K.; Kumar, R.; Kumar, C. R.; Grossert, J. S.; Hooper, D. L. Synth.
Commun. 2001, 31, 3429–3446.
Acknowledgements
13. Crystallographic data (without structure factors) for compound 6 has been
deposited with Cambridge Crystallographic Data Centre, CCDC 854979. These
data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif,
by e-mailing data_request@ccdc.cam.ac.uk, or by contacting CCDC 12 Union
Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
14. Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 16, 4467–4469.
15. Kauffman, G. B.; Teter, L. Inorg. Synth. 1963, 7, 245–249.
16. Grim, S. O.; Keiter, R. L.; McFarlane, W. Inorg. Chem. 1967, 6, 1133–1137.
17. Al-Najjar, I. M. Inorg. Chim. Acta 1987, 128, 93–104.
Thanks to Thomas Cooper, PhD of the Air Force Research Labo-
ratory for financial support of this research. Thanks to Geoffrey
Lindsay, PhD (NAWCWD) for advice and encouragement through-
out the course of this work. Thanks to Ann Moorehead of our Tech-
nical Library for collecting Refs. 6, 10 and 11.
18. Data for bis[trans 1-ethyl-2-(2-(5-ethynylthiophen-2-yl)vinyl)-6-(N-methyl-N-
(2-hydroxyethyl)amino)benzimidazole]bis(tri-n-butylphosphine)platinum (II)
1: Mp 210–212 °C. 1H {31P} NMR (300 MHz, CDCl3): 7.9 (d, J = 15.2 Hz, 2H), 7.6
(d, J = 8.7 Hz, 2H), 6.9 (d, J = 3.5 Hz, 2H), 6.9 (d, J = 8.8 Hz, 2H), 6.8 (d, J = 3.5 Hz,
2H), 6.7 (d, J = 15.3 Hz, 2H), 6.6 (m, 2H), 4.2 (q, J = 7.0 Hz, 4H), 3.9 (t, J = 5.2 Hz,
4H), 3.5 (t, J = 5.6 Hz, 4H), 3.0 (s, 6H), 2.1 (m, 12H), 1.7–1.4 (m, 30 H), 1.3 (s, 2
OH), 0.9 (t, J = 7.0 Hz, 18H); 13C NMR (75 MHz, CDCl3): d 149.2, 147.6, 138.8,
136.6, 136.3, 130.6, 129.2, 128.9, 128.5, 119.5, 118.4, 111.9, 110.7, 102.5, 93.2,
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2012.01.023.
References and notes
60.1, 56.9, 39.8, 38.1, 26.6, 24.6 (t, JC P = 7.0 Hz), 24.2 (t, JC P = 17.1 Hz), 15.4,
c
a
14.0; 31P {1H} NMR (121 MHz, CDCl3): d +4.2 (pseudo t, 1J(P-Pt) = 2327 Hz); 195Pt
1
1. (a) Long, N. J.; Williams, C. K. Angew. Chem., Int. Ed. 2003, 42, 2586–2617; (b)
Manna, J.; John, K. D.; Hopkins, M. D. In Advances in Organometallic Chemistry;
Stone, F. G. A., West, R., Eds.; Academic Press: New York, 1995; Vol. 38,.
2. Rogers, J. E.; Slagle, J. E.; Krein, D. M.; Burke, A. R.; Hall, B. C.; Fratini, A.; McLean,
D. G.; Fleitz, P. A.; Cooper, T. M.; Drobizhev, M.; Makarov, N. S.; Rebane, A.; Kim,
K. –Y.; Farley, R.; Shanze, K. S. Inorg. Chem. 2007, 46, 6483–6494; (b) Casalboni,
M.; Sarcinelli, F.; Pizzoferrato, R.; D’Amato, R.; Furlani, A.; Russo, M. V. Chem.
Phys. Lett. 2000, 319, 107–112.
NMR (64.3 MHz, CDCl3): d À4689.4 (t, JPt-P = 2330 Hz). Elemental analysis
calculated for C64H94N6O2P2PtS2: C, 59.10; H, 7.28; N, 6.46. Found: C, 59.17; H,
7.28; N, 6.56.
19. Sonogashira, K.; Hagihara, N. J. Organomet. Chem. 1978, 145, 101–108.
20. Zeile Krevor, J. V.; Simonis, U.; Richter, J. A., II Inorg. Chem. 1992, 31, 2409–2414.
21. Sadowy, A. L.; Ferguson, M. J.; McDonald, R.; Tykwinski, R. R. Organometallics
2008, 27, 6321–6325.
22. Natarajan, A.; Jean-Gilles, R. P.; Chan, K. P.; Perry, R. J.; Ostroverkhov, V. P.; Kim,
E. M.; Lee, J. L.; Boden, E. P.; Mcclosky, P. J.; Lawrence, B. L. U.S. Patent
Application 20110053054, 3 March 2011.
3. Staromlynska, J.; McKay, T. J.; Bolger, J. A.; Davy, J. R. J. Opt. Soc. Am. B 1998, 15,
1731–1736.
4. Vestberg, R.; Westlund, R.; Eriksson, A.; Lopes, C.; Carlsson, M.;
Eliasson, B.; Glimsdal, E.; Lindgren, M.; Malmström, E. Macromolecules
2006, 39, 2238–2246.
23. Pregosin, P. S.; Kunz, R. Helv. Chim. Acta 1975, 58, 423–431.
24. Pregosin, P. S.; Kunz, R. W. In NMR Basic Principles and Progress; Diehl, P., Fluck,
E., Kosfeld, R., Eds.; Springer: Berlin, 1979; Vol. 16,.
5. Guilard, R.; Fournari, P.; Person, M. Bull. Soc. Chim. France 1967, 4121–4126.
6. Wu, L. –H.; Chu, C. –S.; Janarthanan, N.; Hsu, C. –S. J. Polym. Res. 2000, 7,
125–134.
25. Vives, G.; Carella, A.; Sistach, S.; Launay, J. –P.; Rapenne, G. New J. Chem. 2006,
30, 1429–1438.
26. Keller, J. M.; Schanze, K. S. Organometallics 2009, 28, 4210–4216.