Application of wittig reaction in synthesis of novel pyridine dicarboxylic acid derivatives with high ligand activity

Article abstract of DOI:10.1080/00397911.2010.518275

A series of novel conjugated molecules with two pyridine dicarboxylic acid units have been synthesized by a Wittig reaction of corresponding alkyltriphenylphosphonium salts with aromatic aldehydes. The novel pyridine dicarboxylic acid derivatives with high ligand activity were completely characterized from their mass and ¹H NMR spectra. The E-configuration of these alkenes was confirmed by infrared spectroscopic data.

Full text of DOI:10.1080/00397911.2010.518275

This article was downloaded by: [New Mexico State University]
On: 18 December 2014, At: 15:01
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Application of Wittig Reaction in
Synthesis of Novel Pyridine Dicarboxylic
Acid Derivatives with High Ligand
Activity
Guo-Liang Gu a , Ming Lu a & Rui-Ren Tang b
a Department of Chemical Engineering , Nanjing University of
Science and Technology , Nanjing , China
b School of Chemistry and Chemical Engineering , Central South
University , Changsha , China
Published online: 26 Jul 2011.
To cite this article: Guo-Liang Gu , Ming Lu & Rui-Ren Tang (2011) Application of Wittig Reaction
in Synthesis of Novel Pyridine Dicarboxylic Acid Derivatives with High Ligand Activity, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:22, 3403-3408, DOI: 10.1080/00397911.2010.518275
To link to this article: http://dx.doi.org/10.1080/00397911.2010.518275
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,

systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Synthetic Communications1, 41: 3403–3408, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.518275
APPLICATION OF WITTIG REACTION IN SYNTHESIS OF
NOVEL PYRIDINE DICARBOXYLIC ACID DERIVATIVES
WITH HIGH LIGAND ACTIVITY
Guo-Liang Gu,1 Ming Lu,1 and Rui-Ren Tang2
1Department of Chemical Engineering, Nanjing University of Science and
Technology, Nanjing, China
2School of Chemistry and Chemical Engineering, Central South University,
Changsha, China
GRAPHICAL ABSTRACT
Abstract A series of novel conjugated molecules with two pyridine dicarboxylic acid units
have been synthesized by a Wittig reaction of corresponding alkyltriphenylphosphonium
salts with aromatic aldehydes. The novel pyridine dicarboxylic acid derivatives with high
ligand activity were completely characterized from their mass and 1H NMR spectra. The
E-configuration of these alkenes was confirmed by infrared spectroscopic data.
Keywords Conjugated molecules; pyridine dicarboxylic acid; synthesis; Wittig reaction
INTRODUCTION
The Wittig reaction has been known for more than 50 years and is one of the
most important carbon–carbon double-bond-forming reactions in organic chemis-
try.[1] It has attracted the attention of scientists worldwide because of its numerous
applications in chemical sensing, asymmetric catalysis, material science, and
large-scale reactions in industry.[2,3] The popularity of the Wittig reaction is mainly
a result of the regioselective formation of the double bond at the position of the
former carbonyl group and the possibility of controlling its stereoselectivity by
applying special reaction conditions.[4]
Received November 12, 2009.
Address correspondence to Guo-Liang Gu, Department of Chemical Engineering,
Nanjing University of Science and Technology, Nanjing 210094, China. E-mail: luming@mail.njust.edu.cn
3403

3404
G.-L. GU, M. LU, AND R.-R. TANG
Scheme 1. The synthesis route.
Studies of fluorescent probes in biological media, optical amplification in
fiber-optic telecommunications systems and photoluminescence devices are valu-
able.[5–8] To fully exploit the benefits of these interesting materials, there is a need
for supramolecular systems with antenna units. Antenna molecules have one chro-
mophore at one end of an array that can absorb a photon and the other chromo-
phore at the opposite end of the array that will emit a photon subsequently. In
recent years, some rare-earth complexes with b-diketon, aromatic carboxylic acid,
and heterocyclic carboxylic acid group were under development, such as benzoyl
acetone (BA),[9] benzoyltrifluoroacetone (BFA),[10] a-thenoyltrifluoroacetone
(TTA),[11] and pyridine-2,6-dicarboxylic acid (DPA).[12] Since the lanthanide com-
plexes with DPA derivatives are chiral, they can get more information about struc-
ture of biological molecules through measurement of circularly polarized
luminescence spectra.[13,14] For this purpose, a few elegantly designed donor–
acceptor pairs with one pyridine-2,6-dicarboxylic acid (DPA) compound have been
synthesized and studied.[15] Our continuous interest in the synthesis of compounds
led to the discovery of novel agents comprising two pyridine-2,6-dicarboxylic acid
units because of their high absorption coefficient, strong donating ability, and good
thermal, chemical, and photochemical stability.
Here we report the synthesis and characterization of a series of conjugated
molecules in which two pyridine-2,6-dicarboxylic acid units are linked by a
conjugated carbon–carbon double bond. The possibility that these compounds would
be active stems from the fact that the previously described compounds have rigid

PYRIDINE DICARBOXYLIC ACID DERIVATIVES
3405
conjugated planar structure, which would be beneficial to the electronic negotiabil-
ity.[16] We report the detailed preparation for the compounds in Scheme 1.
RESULTS AND DISCUSSION
4-(Hydroxylmethyl)pyridine-2,6-dicarboxylate (compound 1), p-xylylene bis-
(triphenyl-phosphonium bromide) (compound 8), and 2,6-bis(bromomethyl)pyridine
(compound 5) were synthesized as described in the literatures.[17–19]
The infrared (IR) spectra of compounds 9–11 display strong and sharp bands
at 987–964 cmꢀ1 and 1718–1738 cmꢀ1 assigned to d (¼C-H) and n (–C O) stretch-
=
ing frequencies respectively, and the medium-intensity and wide bands at
=
1654–1635 cmꢀ1 are attributed to n(C C), which suggests compounds 9–11 are
trans-configuration with double bonds. The H NMR spectrum displayed a singlet
1
at d 12.45–12.50, which accounts for the carboxyl proton; a multiplet appeared at
d 7.74–8.37, which accounts for five aromatic protons of the pyridine ring, multiplet
=
appeared at d 6.93–7.83 due to olefinic bond protons on the Py-CH C and
=
Ar-CH C protons.
To examine the thermal stability of the three compounds, thermal gravimetric
(TG) and differential thermal analyses (DTA) were carried out between 150 and
450 ꢁC in the static atmosphere of air. The heating rate is 10 ꢁC=min, and the
TG-DTA curves show the weight loses as the temperature increases. The mass-loss
stage of the three compounds in region of 290–350 ꢁC is attributed to decomposition,
which indicates that they may be large conjugated molecules and would be beneficial
to the electronic negotiability. Also, the two pyridines rings can chelate with two
lanthanide ions respectively to form a p-extended conjugated netted structure, which
increases the fluorescence efficiency.
EXPERIMENTAL
All reagents were obtained commercially and used without further purification.
Melting points were determined on an XR-4 apparatus (thermometer uncorrected).
Contents of carbon, hydrogen, and nitrogen were determined using an Elementar
Vario EL elemental analyzer. IR spectra (4000–400 cmꢀ1) were recorded with sam-
ples as KBr pellets on a Nicolet Nexus 670 Fourier transform (FT)–IR spectrophot-
ometer. 1H NMR were measured with a Bruker 400-MHz nuclear magnetic
resonance spectrometer with CDCl3 or dimethylsulfoxide (DMSO) as solvent and
tetramethylsilane (TMS) as internal reference. Mass spectra were measured using
a ZAB-HS analyzer.
Synthetic Procedure for Compounds
Compound 2. Sulfuryl dichloride (2.4 g, 20.0 mmol) was added dropwise to a
solution of compound 1 (3.0 g, 13.3 mmol) in anhydrous CHCl3 (25 mL) under a
nitrogen atmosphere at ꢀ5 ꢁC with continuous stirring for up to 40 min. Excess
solvent was removed under reduced pressure, and the crude product was purified
by recrystallization from ethanol to give the flaxen solid 2 (2.8 g) after drying in
vacuum.

3406
G.-L. GU, M. LU, AND R.-R. TANG
Compound 5. To a mixture of bromhydric in acetic acid (250 mL), 2.40 g
(26.0 mmol) of pyridine-2,6-dimethanol (compound 4) were added refluxed for
36 h, and then cooled to 0 ꢁC. The solution was concentrated under reduced pressure,
and a whitish solid was obtained. The white precipitate obtained by filtration then
was dissolved in CH2Cl2 and washed with an aqueous solution of Na2CO3. The
organic phases were dried over MgSO4 and evaporated to be dried under vacuum.
Compound 5 was obtained.
Compound 7. Pyridinium chlorochromate (PCC, 11.2 g, 75.0 mmol) was
added to the solution of compound 1 (11.2 g, 50.0 mmol) in dry dichloromethane
(50 mL) at room temperature. After stirring for 5 h, 50% solvent was removed and
ethyl acetate (100 mL) was added. The reaction mixture was washed with water
(80 mL), sodium bicarbonate (5%, 80 mL ꢂ 2), and saturated brine (100 mL) sequen-
tially. The organic layer was separated, dried (Na2SO4), and then concentrated under
reduced pressure. The crude solid product was purified by recrystallization (ethyl
acetate=chloroform, 3:1) to give compound 3 as acicular whitish solid (9.6 g).
Compounds 9–11. A solution of triphenylphosphine (3.4 g, 12.5 mmol) and
compound 2 (2.5 g, 10.0 mmol) in dimethylformamide (DMF) (5 mL) was refluxed
for 5 h and then cooled to room temperature. Anhydrous benzene (15 mL) was
added to the solution and refluxed for 1 h. The reaction mixture was filtered to
obtain the colorless solid 3 (3.5 g). A solution of sodium methanolate (0.4 g,
6.0 mmol) in 20 mL absolute methanol was added dropwise to the absolute methanol
(50 mL) solution of compound 3 (2.6 g, 5.0 mmol) and compound 4 (1.2 g, 5.0 mmol)
stirred up to 1 h under a nitrogen atmosphere at ꢀ20 ꢁC, and kept overnight with
stirring at room temperature. The solution was concentrated under reduced pressure,
and a whitish solid 5 was obtained by flash chromatography, eluting from ethyl acet-
ate, petroleum ether and chloroform (1:1:1, v=v). A solution of NaOH (30%, 18.0 g)
was added to 4-(4-(2-(2,6-bis(methoxycarbonyl)pyridine-4-yl)vinyl)styryl)pyridine-
2,6-dicarboxylate (5.6 g, 10.0 mmol) in methanol (80 mL), and the mixture was
stirred at room temperature for 30 h. Then the pH was adjusted to 1 with HCl
(3 mol=L). The whitish solid 9 (2.9 g) was obtained.
Compounds 10 and 11 were obtained following the same procedure described
as compound 9 starting from compound 6 and compound 8.
Data
Compound 2. Yield: 86.0%; mp 168–170 ꢁC. IR (KBr), n =cmꢀ1: 3079, 2959,
2836, 1725, 1710, 1380, 1257, 1125, 798. MS, m=z: 243 (Mþ), 213 (M-OCH3, 62%),
184 (M-OCH3-CO, 100%). 1H NMR (400 MHz, CDCl3), d (ppm): 8.27 (s, 2H,
Py-H), 4.45 (s, 2H, CH2Cl), 4.06 (s, 6H, OCH3). EA (calculated for C9H10O5N):
% C, 49.65 (49.18); H, 4.15 (4.23); N, 5.52 (5.37).
1
Compound 5. Yield: 53.20%; H NMR (400 MHz, CDCl3), d (ppm): 4.45
(s, 4H, CH2), 7.40 (d, 2H, ArH), 7.80 (t, 1H, ArH). MS, m=z: 265 (Mþ). EA (calcu-
lated for C7H7NBr2): % C, 32.03 (31.73); H 2.57 (2.66), N, 5.23 (5.29).
Compound 7. Yield: 86.0%, mp 152–154 ꢁC; IR (KBr), n=cmꢀ1: 3037, 2960,
2861, 1734, 1706, 1355, 1213, 978, 781. MS m=z: 165 (M-OCH3-CO, 100%). H
1

PYRIDINE DICARBOXYLIC ACID DERIVATIVES
3407
NMR (400 MHz, CDCl3), d (ppm): 10.02 (s, 1H, CHO), 6.64 (s, 2H, Py-H), 4.06 (s,
6H, OCH3). EA (calculated for C9H10O5N): % C, 53.65 (53.82), H 4.10 (4.06); N,
6.30 (6.28).
Compound 9. Yield: 98.4%; mp 286–288 ꢁC. IR (KBr), n=cmꢀ1: 3450, 2918,
1
1734, 1636, 1593, 1399, 1259, 981, 696. H NMR (DMSO-d6), d (ppm): 12.50 (s,
H, COOH), 8.05 (s, 2H, Py-H), 6.96 (d, H, J ¼ 17.0 Hz, Py-CH¼).
Compound 10. Yield: 98.4%; mp 288–290 ꢁC. IR (KBr), n=cmꢀ1: 3456, 2919,
1738, 1635, 1598, 1340, 1257, 987, 685. 1H NMR (DMSO-d6), d (ppm): 6.93 (d, 2H,
¼HC-Py-CH¼), 7.10 (d, 2H, Py-CH¼), 7.74 (s, 1H, Py-H), 7.92 (d, 2H, Py-H), 8.25
(s, H, Py-H), 12.47 (s, H, COOH).
Compound 11. Yield: 96.1%. mp > 300 ꢁC. IR (KBr), n=cmꢀ1: 3448, 2981,
1
1718, 1654, 1594, 1396, 1288, 964. H NMR (400 MHz, DMSO-d6), d (ppm): 7.83
(ds, 2H, J ¼ 17.02 Hz, Ar-CH¼), 7.32 (d, 2H, J ¼ 16.352 Hz, Py-CH¼), 8.37 (s, 4H,
Py-H), 7.68 (s, 4H, Ar-H).
REFERENCES
1. Nicolaou, K. C.; Ha¨rter, M. W.; Gunzner, J. L.; Nadin, A. The Wittig and related
reactions in natural product synthesis. Eur. J. Org. Chem. 1997, 7, 1283–1301.
2. Pommer, H. The Wittig reaction in industrial practice. Angew. Chem. 1977, 89, 437–443.
3. Togni, A.; Hayashi, T. (Eds.). Ferrocenes: Homogeneous Catalysis, Organic Synthesis,
Materials Science. VCH: Weinheim, 1995.
4. Wang, Q.; El Khoury, M.; Schlosser, M. Bridging the final gap in stereo-controlled Wittig
reactions: Methoxymethoxy-armed allylic phosphorus ylides affording conjugated dienes
with high cis-selectivity. Chem. Eur. J. 2000, 6, 420–426.
5. Parker, D. Excitement in f block: Structure, dynamics, and function of nine-coordinate
chiral lanthanide complexes in aqueous media. Chem. Soc. Rev. 2004, 33, 156–165.
6. Bunzli, J. C. G. Benefiting from the unique properties of lanthanide ions. Acc. Chem. Res.
2006, 39, 53–61.
7. Hemmila, I.; Laitala, V. Progress in lanthanides as luminescent probe. J. Fluoresc. 2005,
15, 529–542.
8. Zhang, H. J.; Gou, R. H.; Yan, L.; Yang, R. D. Synthesis, characterization, and lumi-
nescence property of N,N0-di(pyridine N-oxide-2-yl)pyridine-2,6-dicarboxamide and
corresponding lanthanide(III) complexes. Spectrochim. Acta. Part A 2007, 66, 289–294.
9. Meshkova, B. S. The dependence of the luminescence intensity of lanthanide complexes
with b-diketones on the ligand form. J. Fluoresc. 2000, 10, 333–337.
10. Serra, O. A.; Rosa, I. L. V.; Medeiros, C. L.; Zaniquelli, M. E. D. Luminescent properties
of Eu3þ b-diketonate complexes supported on Langmuir—Blodgett films. J. Lumin. 1994,
60–61, 112–114.
11. Zhang, R. J.; Liu, H. G.; Yang, K. Z.; Si, Z. K.; Zhu, G. Y.; Zhang, H. W. Fabrication
and fluorescence characterization of the LB films of luminous rare-earth complexes
Eu(TTA)3 Phen and Sm(TTA)3Phen. Thin Solid Films 1997, 295, 228–233.
12. Yang, M. Y.; Shi, H. H.; Yang, G.; Chen, X. M.; Gu, L. Q. Luminescence of terbium che-
lates with substituted pyridine-2,6-dicarboxylic acid derivatives by synergistic effect of
EDTA. J. Chin. Rare Earth Soc. 2000, 18, 212–215.
13. Sokolnicki, J.; Legendziewicz, J.; Muller, G. and Riehl, J. P. The luminescence, molecular
and electronic structure, and excited state energetics of tris complexes of

3408
G.-L. GU, M. LU, AND R.-R. TANG
4-phenylethynyl-2,6-pyridinedicarboxylic acid with Eu(III) and Tb(III) prepared in
sol-gel. Opt. Mater. 2005, 27, 1529–1536.
14. Morita, M.; Rau, D.; Herren, M. Circularly polarized luminescence and enantiomeric
energy transfer discrimination of chiral Tb(III)–Nd(III) EDDS and related complexes.
J. Alloys Compd. 2004, 380,260–267.
15. Tang, R. R.; Yan, Z. E.; Guo, C. C. Synthesis of Eu(III) and Tb(III) complexes with novel
pyridine-2,6-dicarboxylic acid derivatives and their fluorescence properties. Chem. J. Chin.
Univ. 2006, 27, 472–477.
16. Paul, N. W. Synthesis and properties of a twistophane ion sensor: A new conjugated
macrocyclic ligand for the spectroscopic detection of metal ions. J. Org. Chem. 2001,
66, 4170–4179.
17. Tang, R. R.; Zheng, Y. H.; Zhao, Q.; Yan, Z. E. Synthesis of dimethyl 4-(hydroxymethyl)
pridine-2,6–dicarboxylate. Chem. Rea. Engi. Technol. 2006, 22, 83–87.
18. Puskas, D. R.; Imre, W.; Schmitt, E. F. Process for the manufacture of 1,4-bis [2-(4’–car-
bometh-oxystyr-enyl)] benzene. U.S. Patent 514, 681, 1983.
19. Shi, X. M.; Tang, R. R.; Gu, G. L.; Huang, K. L. Synthesis and fluorescence properties
of lanthanide(III) complexes of a novel bis(pyrazolyl-carboxyl)pyridine-based ligand.
Spectrochim. Acta Part A 2009, 72, 198–203.