Synthesis of novel multifunctional pyridine-2,6-dicarboxylic acid derivatives

Article abstract of DOI:10.1081/SCC-120017186

Eleven novel multifunctional compounds with pyridine-2,6-dicarboxylic acid were synthesized by hydrolyzing of ester prepared by coupling of diethyl 4-hydroxypyridine-2,6-dicarboxylate to bis-halohydrocarbon or bis-halide. All of the new compounds were characterized by ¹H NMR, MS, IR and EA.

Full text of DOI:10.1081/SCC-120017186

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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 7, pp. 1113–1119, 2003
Synthesis of Novel Multifunctional
Pyridine-2,6-dicarboxylic Acid Derivatives
2
Xian-Hong Yin1,2, and Min-Yu Tan
*
1Department of Chemistry, Guangxi University for
Nationalities, Nanning, P.R. China
2Department of Chemistry, LanZhou University,
LanZhou, P.R. China
ABSTRACT
Eleven novel multifunctional compounds with pyridine-2,6-dicar-
boxylic acid were synthesized by hydrolyzing of ester prepared by
coupling of diethyl 4-hydroxypyridine-2,6-dicarboxylate to bis-halo-
hydrocarbon or bis-halide. All of the new compounds were charac-
1
terized by H NMR, MS, IR and EA.
*Correspondence: Xian-Hong Yin, Department of Chemistry, Guangxi
University for Nationalities, Nanning-530006, P.R. China; Department of
Chemistry, LanZhou University, LanZhou-730000, P.R. China. E-mail:
yxhphd@163.net.
1113
DOI: 10.1081/SCC-120017186
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1114
Yin and Tan
Pyridine-2,6-dicarboxylic acid existed largely in biological body.[1]
Prof. Richardson in Virginia university of US adopted chiroptical
luminescence measurements new techniques through pyridine-2,6-dicar-
boxylic acid derivatives to study chirality-dependent molecular excited-
state dynamic, to study excited-state racemization kinetics associated
with intermolecular chiral recognition processes in solution.[2] Many
scholar have a strong interest for studying lanthanide luminescence com-
plexes, because it can be used largely in the chemistry and life science.[3]
Synthesis of the multifunctional, stable, excited-strong luminescence sen-
sitizer is challenge research work in present. Therefore, we have designed
and successfully synthesized a series of novel multifunctional pyridine-
2,6-dicarboxylic acid derivatives. The overall sequence of reactions is
shown in Sch. 1.
EXPERIMENTAL
Infrared spectra were measured on a Perkin-Elmer 1600 FTIR
1
spectrophotometer as KBr pellets. H NMR spectra were recorded on a
Varian Unity 400 NMR spectrometer. Mass spectra were obtained on a
ZAB VG ANALY Mass spectrometer. The elemental analyses with CHN
were performed using a Perkin-Elmer 240C elemental analyzer.
Compound 1, 2, 3 were synthesized respectively by reference.[4–6]
Compound 15 was synthesized by reference.[7] Compound 16, 17 were
synthesized by reference.[8]
General Synthesis Methods as Follow
A mixture of diethyl 4-hydroxypyridine-2,6-dicarboxylate 3 (4.74 g,
19.8 mmol) and anhydrous potassium carbonate (2.48 g, 18 mmol) in
Scheme 1.

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Pyridine-2,6-dicarboxylic Acid Derivatives
1115
Scheme 1. Continued.
(continued)

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1116
Yin and Tan
Scheme 1. Continued.
N,N-dimethylformamide (30 mL) was stirred at 25ꢀC in vacuo for 0.5 h,
then 1,2,3,4,5,6-six(bromomethyl)benzene (1.9 g, 3 mmol) was added and
the reaction mixture was allowed to react at 70–80ꢀC for 50 h under an
atmosphere of argon. The mixture was evaporated in vacuo and the
residue was partitioned between dichloromethane (200 mL) and water
(50 mL). The organic layer was washed with 1% aqueous acetic acid,
water and dried (sodiumsulfate). The residue obtained, after removal
of the solvent, was recrystallized fromethanol. 40 mL 2 M sodiumhydro-
xide was added, the mixture was refluxed for 3 h, filtered and the filtrate
acidified with 3 M hydrochloric acid. The solid was collected and recrys-
tallized several times from water and dried in vacuo at 50ꢀC to give 2.54 g
(68%) of Compound 12.
A mixture of dimethyl 4-chloropyridine-2,6-dicarboxylate (4.58 g,
20 mmol), thiourea (1.52 g, 20 mmol) and methanol (50 mL) was refluxed
for 3 h. After cooling the solid was filtered, recrystallized fromdioxane to
give bis(2,6-dicarbomethoxy-4-pyridyl) sulfide. It was followed by hydro-
lysis and dried to give 2.86 g (78%) of Compound 13.
All products were characterized by NMR, IR, MS and EA.
1
Compound 2. H NMR (90 MHz, DMSO-d6), ꢀ: 7.54 (2H, s, Py-H),
8.11 (3H, OH þ 2COOH). IR (KBr): 3606, 3444, 3121, 1728, 1616,
1468 cmꢁ1. m/z (FAB): 183 (M þ1).
Compound 3. 1H NMR (90 MHz, CDCl3), ꢀ: 7.28 (2H, s, Py-H), 4.45
(4H, q, 2CH2), 1.4 (6H, t, 2CH3).
1
Compound 15. H NMR (CDCl3), ꢀ: 8.31 (2H, s, Ph-H), 4.05 (6H, s,
COOCH3).
1
Compound 16. H NMR (CDCl3), ꢀ: 7.21–8.0 (5H, m, Ph-H), 2.87
(3H, s, 1-CH3), 2.61 (3H, s, 3-CH3). IR (KBr): 3057, 2952, 2917,
1623–1496, 1440, 1398, 751 cmꢁ1
.

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Pyridine-2,6-dicarboxylic Acid Derivatives
1117
1
Compound 17. H NMR (CDCl3), ꢀ: 8.25 (1H, d, Ph-H), 7.86 (1H, s,
Ph-H), 7.77 (3H, m, Ph-H), 5.03 (2H, s, 1-CH2Br), 4.72 (2H, s, 3-CH2Br).
IR (KBr): 3057, 2987, 1616–1496, 1384, 1342, 751, 617, 561 cmꢁ1. m/z
(FAB): 315 (Mþ).
1
Compound 4. H NMR (90 MHz, DMSO-d6), ꢀ: 7.68 (4H, s, Pr-H),
4.38 (4H, t, OCH2). 1.98 (4H, m, CH2CH2). IR (KBr): 3425, 3089, 2959,
2530, 1725, 1597, 1457, 1383, 1304, 1222, 1110, 1025, 893, 776, 689 cmꢁ1
.
m/z (FAB): 420 (Mþ). Anal. calcd. for C18H16N2O10: C 51.43, H 3.84, N
6.66. Found: C 51.51, H 3.67, N 6.78.
1
Compound 5. H NMR (90 MHz, DMSO-d6), ꢀ: 7.68 (4H, s, Pr-H),
4.36 (4H, t, CH2OPy), 3.89 (4H, t, OCH2). IR (KBr): 3416, 3093, 2924,
2600, 1714, 1602, 1454, 1391, 1243, 1124, 1053, 688 cm-1. m/z (FAB): 436
(Mþ). Anal. calcd. for C18H16N2O11: C 49.55, H 3.70, N 6.42. Found: C
49.46, H 3.84, N 6.57.
1
Compound 6. H NMR (90 MHz, DMSO-d6), ꢀ: 7.69 (4H, s, Pr-H),
4.36 (4H, t, CH2OPy), 3.84 (4H, t, OCH2), 3.62 (4H, s, CH2CH2). IR
(KBr): 3444, 3085, 2938, 2898, 2586, 1735, 1637, 1602, 1419, 1363, 1314,
1236, 1117, 1053, 793 cmꢁ1. m/z (FAB): 481 (M þ1). Anal. calcd.
for C20H20N2O12: C 50.00, H 4.20, N 5.83. Found: C 50.12, H 4.43,
N 5.77.
1
Compound 7. H NMR (90 MHz, DMSO-d6), ꢀ: 7.78 (4H, s, Py-H),
4.37 (4H, m, CH2OPy), 3.78 (4H, m, OCH2), 3.65 (8H, s, CH2CH2). IR
(KBr): 3613, 3458, 3310, 3121, 2924, 2874, 2706, 2544, 1735, 1616, 1475,
1398, 1342, 1250, 1131, 1018, 899, 793 cm-1. m/z (FAB): 525 (M þ1).
Anal. calcd. for C22H24N2O13: C 50.38, H 4.61, N 5.34. Found: C
50.42, H 4.54, N 5.46.
1
Compound 8. H NMR (90 MHz, DMSO-d6), ꢀ: 7.80 (4H, s, Py-H),
7.52 (4H, d, Ph-H), 5.50 (4H, s, Ph-CH2). IR (KBr): 3514, 3395,
3100–2845, 2546, 1743, 1602, 1461, 1384, 1342, 1307, 1194, 1110, 1032,
758 cmꢁ1. m/z (FAB): 469 (M þ1). Anal. calcd. for C22H16N2O10: C
56.42, H 3.44, N 5.98. Found: C 56.34, H 3.56, N 6.17.
1
Compound 9. H NMR (90 MHz, DMSO-d6), ꢀ: 7.81 (4H, s, Py-H),
7.62 (1H, s, Ph-H), 7.49 (3H, s, Ph-H), 5.39 (4H, s, Ph-CH2). IR (KBr):
3451, 3254, 3093, 2945–2780, 2534, 1728, 1595, 1465, 1370, 1314, 1194,
1110, 1039, 793, 695 cmꢁ1. m/z (FAB): 469 (M þ1). Anal. calcd.
for C22H16N2O10: C 56.42, H 3.44, N 5.98. Found: C 56.32, H 3.57,
N 6.12.
1
Compound 10. H NMR (90 MHz, DMSO-d6), ꢀ: 7.80 (4H, s, Py-H),
7.50 (4H, d, Ph-H), 5.40 (4H, s, Ph-CH2). IR (KBr): 3514, 3332, 3107,
2931, 2896, 2523, 1728, 1637, 1595, 1405, 1342, 1264, 1117, 1025,
793 cmꢁ1. m/z (FAB): 469 (M þ1). Anal. calcd. for C22H16N2O10: C
56.42, H 3.44, N 5.98. Found: C 56.40, H 3.54, N 5.93.

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1118
Yin and Tan
1
Compound 11. H NMR (90 MHz, DMSO-d6), ꢀ: 7.82 (8H, s, Py-H),
7.68 (2H, s, Ph-H), 5.55 (8H, s, Ph-CH2). Anal. calcd. for C38H26N4O20:
C 53.16, H 3.05, N 6.53. Found: C 53.20, H 3.16, N 6.47.
Compound 12. 1H NMR (90 MHz, DMSO-d6), ꢀ: 7.82 (12H, s, Py-H),
5.58 (12H, s, Ph-CH2). IR (KBr): 3521, 3258, 3105, 2874, 2513, 1720,
1596, 1367, 1306, 1116, 1025, 905, 794 cmꢁ1. Anal. calcd. for
C54H36N6O30: C 51.93, H 2.91, N 6.73. Found: C 51.86, H 2.99, N 6.65.
1
Compound 13. H NMR (90 MHz, DMSO-d6), ꢀ: 8.31 (4H, s, Py-H).
IR (KBr): 3444, 3071, 2931–2780, 2523, 1714, 1644, 1384, 1285, 1236,
1173, 688 cmꢁ1. m/z (FAB): 365 (M þ1). Anal. calcd. for C14H8N2O8S: C
46.16, H 2.21, N 7.69. Found: C 46.08, H 2.32, N 7.75.
Compound 14. 1H NMR (90 MHz, DMSO-d6), ꢀ: 8.76 (1H, d, Ph-H),
8.46 (1H, d, Ph-H), 8.35 (1H, s, Ph-H), 8.27 (1H, d, Ph-H ), 8.24 (1H, d,
A-H ), 7.87 (4H, s, Py-H). 5.87 (2H, s, 1-CH2O), 5.51 (2H, s, 3-CH2O), IR
(KBr): 3462, 3265, 3063, 2984–2786, 2563, 1732, 1618–1494, 1374, 1332,
1187, 1115, 1038, 753 cmꢁ1. m/z (FAB): 520 (M þ1). Anal. calcd. for
C25H17N3O10: C 57.81, H 3.30, N 8.09. Found: C 57.72, H 3.36, N 8.17.
ACKNOWLEDGMENTS
We gratefully acknowledge support of this work by the National
Science Foundation of Guangxi Province (No. 0135009).
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Pyridine-2,6-dicarboxylic Acid Derivatives
1119
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Received in Japan February 11, 2002

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