Home A simple and efficient synthesis of novel naphthyridine-1-H-pyrazole-4-carboxylic acid esters/carbaldehydes using Vilsmeier-Haack reagent
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A simple and efficient synthesis of novel naphthyridine-1-H-pyrazole-4-carboxylic acid esters/carbaldehydes using Vilsmeier-Haack reagent

  • Muggu V.S.R.K. Chaitanya EMAIL logo and Pramod K. Dubey
Published/Copyright: January 18, 2013
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Heterocyclic Communications
From the journal Heterocyclic Communications Volume 19 Issue 1

Abstract

The reaction of hydrazide 4 with β-keto esters 5 gave hydrazones 6. Cyclization of 6 with Vilsmeier-Haack reagent (DMF-POCl3) for 20 min at room temperature gave 1-(4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-1H-pyrazole-4-carboxylic acid ethyl esters 7. The treatment of 4 with substituted acetophenones 8 yielded the corresponding hydrazones 9 of substituted acetophenones. The treatment of 9 with Vilsmeier-Haack reagent (DMF-POCl3) for 30 min at room temperature gave product 10, the reaction of which with (diacetoxyiodo)benzene in ethanol at room temperature for 12 h in the presence of molecular iodine furnished 7.

Keywords: (diacetoxyiodo)benzene; hydrazide; β-keto esters; naphthyridine; substituted acetophenone; Vilsmeier-Haack reagent

Introduction

Pyrazoles possess a wide range of useful biological activities such as antibacterial [1–5], anti-inflammatory [6–9], and antiviral [10, 11] properties. They are also useful luminescent and fluorescent [12] substances and an important class of chemicals in the development of cine films. Pyrimidinopyrazoles are being studied as drug candidates against cancer [13]. In continuation of earlier work on the synthesis of naphthyridinonoes [14, 15], it was considered worthwhile to prepare naphthyridine derivatives containing a pyrazolyl group as compounds with potentially useful biological properties.

Results and discussion

The starting hydrazide 4 was prepared as described previously [16] as summarized in Scheme 1. Condensation of 2-aminopyridine 1 with ethoxymethylenemalonic ester in ethanol under reflux conditions for 4 h yielded the intermediate product 2 [17], the thermal cyclization of which in polyphosphoric acid for 30 min resulted in the formation of 1,8-naphthyridine derivative 3 [17]. Treatment of 3 with hydrazine hydrate in ethanol for 3 h yielded 4.

Scheme 1
Scheme 1

Treatment of 4a with methyl acetoacetate (5a) in methanol under reflux conditions for 1 h yielded product 6a. Cyclization of 6a using Vilsmeier-Haack reagent (DMF-POCl3) at room temperature for 20 min yielded 3-methyl-1-(4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-1H-pyrazole-4-carboxylic acid methyl ester (7a). The 1H NMR spectrum of 7a shows the disappearance of the methylene proton signal and N-N-H proton signal that are observed in the spectrum of the substrate 6a. The proton signal for the newly formed pyrazole ring appears at δ 8.27. This structure is also fully consistent with mass spectral and elemental analysis data.

This series of transformations was successfully extended on the preparations of the corresponding analogs 6b–h and 7b–h. All these products were fully characterized as discussed above for 6a and 7a.

Substrates 4a,b were also allowed to react with substituted acetophenones 8a–e to give the corresponding hydrazides 9a–j (Scheme 2). The treatment of 9a–j with Vilsmeier-Haack reagent at room temperature for 30 min caused cyclization to yield the corresponding products 10a–j. Further, 10a was treated with (diacetoxyiodo) benzene in ethanol in the presence of molecular iodine at room temperature for 12 h. This reaction furnished product which was found to be identical with 7e obtained is discussed above. This interesting transformation involves oxidation of the aldehyde function of 10a followed by esterification of the resultant intermediate carboxylic acid or its derivative.

Scheme 2
Scheme 2

Conclusion

Simple methods for the preparation of 3-methyl-1-(4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-1H-pyrazole-4-carboxylic acid methyl esters 7 and 1-(4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-3-phenyl-1H-pyrazole-4-carbaldehydes 10 using a Vilsmeier-Haack reagent are reported.

Experimental section

All reagents used in this work were obtained from commercial suppliers. Solvents were freshly distilled before use. Melting points are uncorrected and were determined using open capillary tubes in a sulfuric acid bath. TLC analyses were done on glass plates coated with silica gel GF-254 and visualization was done using treatment with iodine or illumination with a UV lamp. IR spectra were recorded on a Perkin-Elmer model 1000 instrument in KBr pellets. 1H NMR spectra were recorded in DMSO-d6 on a 400-MHz Varian Gemini spectrometer. Electrospray ionization mass spectra were recorded on an Agilent LC-MS instrument. Elemental analyses were performed on a Varian 3LV analyzer series CHN analyzer.

General procedure for the preparation of 6

A mixture of 4 (10 mmol), β-ketoester (5a–d) (10 mmol) and methanol (20 mL) was heated under reflux for 1 h and then poured into ice-cold water (25 mL). The separated solid was filtered, washed with water (2×20 mL) and dried, and crystallized from ethanol to give analytically pure product 6a–h.

3-[(4-Oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-hydrazono]-butyric acid methyl ester (6a)

Yield 2.23 g (74%); mp 164–166°C; IR: 3100–2800 (broad, medium, -NH- stretching), 1735 (strong, sharp, O-C=O stretching), 1678 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.25 (s, 3H, -CH3), 2.00 (s, 3H, -CH3), 4.20 (s, 2H, CH2), 7.62–8.26 (m, 3H, Ar-H), 9.11 (s, 1H, -CH, α-proton to the enamine nitrogen), 9.25 (s, 1H, -NH), 11.85 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 303 [M+H]+. Anal. Calcd for C14H14N4O4: C, 55.63; H, 4.67; N, 18.53. Found: C, 55.60; H, 4.64; N, 18.51.

3-[(6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-hydrazono]-butyric acid methyl ester (6b)

Yield 3.0 g (80%); mp 172–174°C; IR: 3400–3000 (broad, medium, -NH- stretching), 1710 (strong, sharp, -O-C=O stretching), 1677 (strong, sharp, -C=O) cm-1; 1H NMR: δ 1.25 (s, 3H, -CH3), 2.10 (s, 3H, -CH3), 4.32 (s, 2H, CH2), 7.84–8.29 (m, 2H, Ar-H), 9.17 (s, 1H, -CH, α-proton to the enamine nitrogen), 9.50 (s, 1H, CH), 11.90 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 382 [M+H]+. Anal. Calcd for C14H13BrN4O4: C, 44.11; H, 3.44; N, 14.70. Found: C, 44.10; H, 3.42; N, 14.68.

3-[(4-Oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-hydrazono]-butyric acid ethyl ester (6c)

Yield 2.6 g (82%); mp 178–180°C; IR: 3400–3100 (broad, medium, -NH- stretching), 1725 (strong, sharp, -O-C=O stretching), 1689 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.20 (s, 3H, -CH3), 2.20 (t, 3H, -CH3), 3.32 (q, 2H, -CH2), 4.17 (s, 2H, CH2), 7.42–8.26 (m, 3H, Ar-H), 8.65 (s, 1H, CH, α-proton to the enamine nitrogen), 9.89 (s, 1H, -NH), 11.85 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 317 [M+H]+. Anal. Calcd for C15H16N4O4: C, 56.96; H, 5.10; N, 17.71. Found: C, 56.94; H, 5.07; N, 17.68.

3-[(6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-hydrazono]-butyric acid methyl ester (6d)

Yield 3.0 g (78%); mp 186°C; IR: 3458–3026 (broad, medium, -NH-), 1716 (strong, sharp, -O-C=O stretching), 1697 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.23 (s, 3H, -CH3), 2.27 (t, 3H, -CH3), 3.35 (q, 2H, -CH2), 4.20 (s, 2H, CH2), 7.78–8.16 (m, 2H, Ar-H), 8.74 (s, 1H, CH, α-proton to the enamine nitrogen), 9.79 (s, 1H, -NH), 11.90 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 396 [M+H]+. Anal. Calcd for C15H15BrN4O4: C, 45.59; H, 3.83; N, 14.18. Found: C, 45.56; H, 3.80; N, 14.16.

3-[(4-Oxo-1,4-dihydro-[1,8]naphthyridine-3-cabonyl)-hydrazono]-3-phenyl-propionic acid ethyl ester (6e)

Yield 3.34 g (88%); mp 256–258°C; IR: 3400–3100 (sharp, medium, -NH- stretching), 1690 (strong, sharp, -O-C=O stretching), 1667 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.30 (t, 3H, -CH3), 2.70 (q, 2H, -CH2), 4.15 (s, 2H, -CH2), 7.16–8.35 (m, 8H, Ar-H), 8.67 (s, 1H, -CH, α-proton to the enamine nitrogen), 9.76 (s, 1H, -NH), 12.00 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 379 [M+H]+. Anal. Calcd for C20H18N4O4: C, 63.48; H, 4.79; N, 14.81. Found: C, 63.45; H, 4.76; N, 14.80.

3-[(6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-cabonyl)-hydrazono]-3-phenyl-propionic acid ethyl ester (6f)

Yield 3.89 g (85%); mp 262–264°C; IR: 3300–3000 (sharp, medium, -NH- stretching), 1710 (strong, sharp, -O-C=O stretching), 1678 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.36 (t, 3H, -CH3), 2.73 (q, 2H, -CH2), 4.18 (s, 2H, -CH2), 7.25–8.18 (m, 7H, Ar-H), 8.59 (s, 1H, -CH, α-proton to the enamine nitrogen), 9.62 (s, 1H, -NH), 11.45 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 458 [M+H]+. Anal. Calcd for C20H17BrN4O4: C, 52.53; H, 3.75; N, 12.25. Found: C, 52.51; H, 3.70; N, 12.23.

4-Chloro-3-[(4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-hydrazono]-butyric acid ethyl ester (6g)

Yield 2.73 g (78%); mp 221–223°C; IR: 3400–3100 (sharp, medium, -NH- stretching), 1738 (strong, sharp, -O-C=O stretching), 1676 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.28 (t, 3H, -CH3), 2.59 (q, 2H, -CH2), 3.42 (s, 2H, -CH2), 4.15 (s, 2H, -CH2), 7.84–8.43 (m, 3H, Ar-H), 8.80 (s, 1H, -CH, α-proton to the enamine nitrogen), 9.56 (s, 1H, -NH), 12.10 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 351 [M+H]+. Anal. Calcd for C15H15ClN4O4: C, 51.36; H, 4.31; N, 15.97. Found: C, 51.34; H, 4.30; N, 15.96.

3-[(6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-hydrazono]-4-chloro-butyric acid ethyl ester (6h)

Yield 3.23 g (75%); mp 230–232°C; IR: 3400–3100 (sharp, medium, -NH- stretching), 1738 (strong, sharp, -O-C=O stretching), 1676 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.30 (t, 3H, -CH3), 2.78 (q, 2H, -CH2), 3.60 (s, 2H, -CH2), 4.27 (s, 2H, -CH2), 7.94–8.27 (m, 2H, Ar-H), 8.87 (s, 1H, -CH, α-proton to the enamine nitrogen), 9.66 (s, 1H, -NH), 11.25 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 431 [M+H]+. Anal. Calcd for C15H14ClBrN4O4: C, 41.93; H, 3.28; N, 13.04. Found: C, 41.90; H, 3.26; N, 13.00.

General procedure for the preparation of 7

POCl3 (4.5 mL, 30 mmol) was added dropwise to an ice-cold, stirred DMF (4 mL) and the mixture was stirred for 30 min before portion-wise treatment with hydrazone 6a–h (10 mmol) for approximately 15 min. The mixture was stirred for an additional 20 min at room temperature and then poured onto crushed ice (25 mL) and neutralized with aqueous solution of NaOH (5%, 10 mL). The separated solid of 7a–h was filtered, washed with water (2×10 mL) and dried, and crystallized from hot ethanol.

3-Methyl-1-(4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-1H-pyrazole-4-carboxylic acid methyl ester (7a)

Yield 1.86 g (60%); mp 174–176°C; IR: 3431–2800 (broad, medium, -NH- stretching), 1710 (strong, sharp, -O-C=O stretching), 1685 and 1660 cm-1 (sharp, strong, -CO- stretching); 1H NMR: δ 1.34 (s, 3H, -CH3), 4.26 (s, 3H, -CH3), 7.42–7.97 (m, 3H, Ar-H), 8.15 (s, 1H, pyrazole-CH), 9.26 (s, 1H, CH, α-proton to the enamine nitrogen), 12.27 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 313 [M+H]+. Anal. Calcd for C15H12N4O4: C, 57.69; H, 3.87; N, 17.94. Found: C, 57.66; H, 3.86; N, 17.90.

1-(6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-3-methyl-1H-pyrazole-4-carboxylic acid methyl ester (7b)

Yield 2.43 g (62%); mp 190–192°C; IR: 3400–2800 (broad, medium, -NH- stretching), 1710 (sharp, strong, -O-C=O stretching), 1698 and 1665 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.20 (s, 3H, -CH3), 3.35 (s, 3H, -CH3), 7.78–8.29 (m, 2H, Ar-H), 8.24 (s, 1H, pyrazole -CH), 9.10 (s, 1H, CH, α-proton to the enamine nitrogen), 11.90 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 392 [M+H]+. Anal. Calcd for C15H11BrN4O4: C, 46.06; H, 2.83; N, 14.32. Found: C, 46.04; H, 2.82; N, 14.30.

3-Methyl-1-(4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-1H-pyrazole-4-carboxylic acid ethyl ester (7c)

Yield 2.15 g (66%); mp 202–204°C; IR: 3300–2900 (broad, medium, -NH- stretching), 1718 (sharp, strong, -O-C=O stretching), 1695 and 1676 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.22 (t, 3H, -CH3), 3.27 (s, 2H, -CH3), 4.12 (q, 2H, -CH2), 7.48–8.37 (m, 3H, Ar-H), 8.55 (s, 1H, pyrazole -CH, α-proton to the enamine nitrogen), 8.90 (s, 1H, -CH), 12.50 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 327 [M+H]+. Anal. Calcd for C16H14N4O4: C, 58.89; H, 4.32; N, 17.17. Found: C, 58.87; H, 4.30; N, 17.15.

1-(6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-3-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (7d)

Yield 2.91 g (72%); mp 212–214°C; IR: 3500–3200 (broad, medium, -NH- stretching), 1728 (sharp, strong, -O-C=O stretching), 1699 and 1665 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.27 (t, 3H, -CH3), 3.40 (s, 2H, -CH3), 4.16 (q, 2H, -CH2), 7.88–8.24 (m, 3H, Ar-H), 8.47 (s, 1H, pyrazole -CH), 9.00 (s, 1H, -CH, α-proton to the enamine nitrogen), 12.15 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 406 [M+H]+. Anal. Calcd for C16H13BrN4O4: C, 47.43; H, 3.23; N, 13.83. Found: C, 47.42; H, 3.20; N, 13.81.

1-(4-Oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-3-phenyl-1H-pyrazole-4-carboxylic acid ethyl ester (7e)

Yield 2.32 g (60%); mp 233–235°C; IR: 3400–3100 (broad, medium, -NH- stretching), 1746 (sharp, strong, -O-C=O stretching), 1690 and 1669 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.17 (t, 3H, -CH3), 4.19 (q, 2H, -CH2), 7.37–8.25 (m, 8H, Ar-H), 8.45 (s, 1H, pyrazole -CH), 9.10 (s, 1H, -CH, α-proton to the enamine nitrogen), 12.15 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 389 [M+H]+. Anal. Calcd for C21H16N4O4: C, 64.94; H, 4.15; N, 14.43. Found: C, 64.90; H, 4.12; N, 14.40.

1-(6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-3-phenyl-1H-pyrazole-4-carboxylic acid ethyl ester (7f)

Yield 3.12 g (67%); mp 237–239°C; IR: 3400–3000 (broad, medium, -NH- stretching), 1716 (sharp, strong, -O-C=O stretching), 1686 and 1660 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.18 (t, 3H, -CH3), 4.25 (q, 2H, -CH2), 7.45–8.16 (m, 7H, Ar-H), 8.34 (s, 1H, pyrazole -CH), 8.95 (s, 1H, -CH, α-proton to the enamine nitrogen), 12.20 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 468 [M+H]+. Anal. Calcd for C21H15BrN4O4: C, 53.98; H, 3.24; N, 11.99. Found: C, 53.95; H, 3.21; N, 11.97.

3-Chloromethyl-1-(4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-1H-pyrazole-4-carboxylic acid ethyl ester (7g)

Yield 2.08 g (58%); mp 192–194°C; IR: 3300–3100 (broad, medium, due to -NH- stretching), 1705 (sharp, strong, due to -O-C=O stretching), 1694 and 1676 cm-1 (strong, sharp, due to -CO- stretching); 1H NMR: δ 1.12 (t, 3H, -CH3), 4.12 (s, 2H, -CH2), 4.18 (q, 2H, -CH2), 7.74–8.23 (m, 3H, Ar-H), 8.21 (s, 1H, pyrazole-CH), 8.94 (s, 1H, CH, α-proton to the enamine nitrogen), 12.13 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 361 [M+H]+. Anal. Calcd for C16H13ClN4O4: C, 53.27; H, 3.63; N, 15.53. Found: C, 53.25; H, 3.62; N, 15.51.

1-(6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-3-chloromethyl-1H-pyrazole-4-carboxylic acid ethyl ester (7h)

Yield 2.64 g (60%); mp 149–151°C; IR: 3400–3100 (broad, medium, -NH- stretching), 1726 (sharp, strong, -O-C=O stretching), 1698 and 1686 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.19 (t, 3H, -CH3), 4.16 (s, 2H, -CH2), 4.25 (q, 2H, -CH2), 7.90–8.13 (m, 2H, Ar-H), 8.35 (s, 1H, pyrazole-CH), 9.10 (s, 1H, CH, α-proton to the enamine nitrogen), 11.55 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 440 [M+H]+. Anal. Calcd for C16H12BrClN4O4: C, 43.71; H, 2.75; N, 12.74. Found: C, 43.69; H, 2.73; N, 12.72.

General procedure for the preparation of 9

A mixture of 4 (10 mmol), substituted acetophenone 8a–j (10 mmol) and ethanol (20 mL) was heated under reflux for 1 h, then cooled and poured onto crushed ice (25 mL). The separated solid of 9a–j was filtered, washed with water (2×10 mL), dried and crystallized from ethanol.

4-Oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid (1-phenyl-ethylidene)-hydrazide (9a)

Yield 2.23 g (73%); mp 135–137°C; IR: 3400–3100 (broad, medium, -NH- stretching), 1684 (strong, sharp, -CO- stretching), 1665 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.22 (s, 3H, -CH3), 7.29–8.30 (m, 8H, Ar-H), 9.24 (s, 1H, -CH, α-proton of the enamino nitrogen), 12.27 (s, 1H, -NH), 13.04 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 307 [M+H]+. Anal. Calcd for C17H14N4O2: C, 66.66; H, 4.61; N, 18.29. Found: C, 66.64; H, 4.59; N, 18.26.

6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid (1-phenyl-ethylidene)-hydrazide (9b)

Yield 2.88 g (75%); mp 142–144°C; IR: 3400–3100 (broad, medium, -NH- stretching), 1688 (strong, sharp, -CO- stretching), 1675 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.27 (s, 3H, -CH3), 7.29–8.32 (m, 7H, Ar-H), 9.24 (s, 1H, -CH, α-proton to the enamine nitrogen), 10.24 (s, 1H, -NH), 12.10 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 386 [M+H]+. Anal. Calcd for C17H13BrN4O2: C, 53.00; H, 3.40; N, 14.54. Found: C, 52.98; H, 3.36; N, 14.5.

4-Oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid [1-(4-chloro-phenyl)-ethylidene]-hydrazide (9c)

Yield 2.65 g (78%); mp 136–138°C; IR: 3400–3100 (broad, medium, -NH- stretching), 1684 (strong, sharp, -CO- stretching), 1669 cm-1 (strong, sharp, -O- stretching); 1H NMR: δ 1.20 (s, 3H, -CH3), 7.25–8.39 (m, 7H, Ar-H), 8.91 (s, 1H, -CH, α-proton to the enamine nitrogen), 10.16 (s, 1H, -NH), 11.12 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 341 [M+H]+. Anal. Calcd for C17H13ClN4O2: C, 59.92; H, 3.85; N, 16.44. Found: C, 59.90; H, 3.80; N, 16.40.

6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid [1-(4-chloro-phenyl)-ethylidene]-hydrazide (9d)

Yield 2.98 g (71%); mp 148–150°C; IR: 3400–3000 (broad, medium, -NH- stretching), 1684 (strong, sharp, -CO- stretching), 1670 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.26 (s, 3H, -CH3), 7.48–8.30 (m, 6H, Ar-H), 8.88 (s, 1H, -CH, α-proton to the enamine nitrogen), 10.26 (s, 1H, -NH), 11.79 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 420 [M+H]+. Anal. Calcd for C17H12BrClN4O2: C, 48.65; H, 2.88; N, 13.35. Found: C, 48.64; H, 2.86; N, 13.30.

4-Oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid [1-(4-nitro-phenyl)-ethylidene]-hydrazide (9e)

Yield 2.94 g (84%); mp162–164°C; IR: 3400–2900 (broad, medium, -NH- stretching), (strong, sharp, -CO- stretching), 1668 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.26 (s, 3H, -CH3), 7.28–8.40 (m, 7H, Ar-H), 8.90 (s, 1H, -CH, α-proton to the enamine nitrogen), 10.25 (s, 1H, -NH), 12.10 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 352 [M+H]+. Anal. Calcd for C17H13N5O4: C, 58.12; H, 3.73; N, 19.93. Found: C, 58.10; H, 3.71; N, 19.90.

6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid [1-(4-nitro-phenyl)-ethylidene]-hydrazide (9f)

Yield 3.50 g (81%); mp 177–179°C; IR: 3300–3000 (broad, medium, -NH- stretching), 1694 (strong, sharp, -CO- stretching), 1678 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.30 (s, 3H, -CH3), 7.18–8.35 (m, 6H, Ar-H), 8.11 (s, 1H, -CH, α-proton to the enamine nitrogen), 9.98 (s, 1H, -NH), 11.45 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 431 [5+H]+. Anal. Calcd for C17H12BrN5O4: C, 47.46; H, 2.81; N, 16.28. Found: C, 47.43; H, 2.80; N, 16.26.

4-Oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid [1-(4-methyl-phenyl)-ethylidene]-hydrazide (9g)

Yield 2.30 g (72%); mp 134–136°C; IR: 3400–3200 (broad, medium, -NH- stretching), 1692 (strong, sharp, -CO- stretching), 1665 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.25 (s, 3H, -CH3), 2.30 (s, 3H, -CH3), 7.28–8.19 (m, 7H, Ar-H), 8.90 (s, 1H, -CH, α-proton to the enamine nitrogen), 10.16 (s, 1H, -NH), 12.55 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 321 [M+H]+. Anal. Calcd for C18H16N4O2: C, 67.49; H, 5.03; N, 17.49. Found: C, 67.46; H, 5.00; N, 17.46.

6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid [1-(4-methyl-phenyl)-ethylidene]-hydrazide (9h)

Yield 3.15 g (79%); mp 138–140°C; IR: 3400–3000 (broad, medium, -NH- stretching), 1699 (strong, sharp, -CO- stretching), 1670 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.32 (s, 3H, -CH3), 2.29 (s, 3H, -CH3), 7.19–8.40 (m, 6H, Ar-H), 8.86 (s, 1H, -CH, α-proton to the enamine nitrogen), 10.05 (s, 1H, -NH), 12.65 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 400 [M+H]+. Anal. Calcd for C18H15BrN4O2: C, 54.15; H, 3.79; N, 14.03. Found: C, 54.12; H, 3.76; N, 14.00.

4-Oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid [1-(4-methoxy-phenyl)-ethylidene]-hydrazide (9i)

Yield 2.35 g (70%); mp 152–154°C; IR: 3400–3150 (broad, medium, -NH- stretching) 1690 (strong, sharp, -CO- stretching), 1674 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.25 (s, 3H, -CH3), 2.56 (s, 3H, -CH3), 7.10–8.20 (m, 7H, Ar-H), 8.80 (s, 1H, -CH, α-proton to the enamine nitrogen), 10.15 (s, 1H, -NH), 12.55 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 337 [M+H]+. Anal. Calcd for C18H16N4O3: C, 64.28; H, 4.79; N, 16.66. Found: C, 64.24; H, 4.73; N, 16.64.

6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid [1-(4-methoxy-phenyl)-ethylidene]-hydrazide (9j)

Yield 2.98 g (72%); mp 158–160°C; IR: 3400–3150 (broad, medium, -NH- stretching), 1710 (strong, sharp, -CO- stretching), 1676 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 1.20 (s, 3H, -CH3), 2.31 (s, 3H, -CH3), 7.27–8.40 (m, 6H, Ar-H), 8.90 (s, 1H, -CH, α-proton to the enamine nitrogen), 10.50 (s, 1H, -NH), 12.99 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 416 [M+H]+. Anal. Calcd for C18H15BrN4O3: C, 52.06; H, 3.64; N, 13.49. Found: C, 52.02; H, 3.62; N, 13.46.

General procedure for the preparation of 10

Products 10 were obtained from 9 by using the procedure described above for the preparation of 7.

1-(4-Oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-3-phenyl-1H-pyrazole-4-carbaldehyde (10a)

Yield 2.33 g (68%); mp 182–184°C; IR: 3400–3100 (broad, medium, -NH- stretching), 1695 (strong, sharp, -CO- stretching), 1684 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 7.10–8.32 (m, 8H, Ar-H), 8.60 (s, 1H, -CH, α-proton to the enamino nitrogen), 9.10 (s, 1H, -CHO), 9.30 (s, 1H, pyrazole-CH), 10.20 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 345 [M+H]+. Anal. Calcd for C19H12N4O3: C, 66.28; H, 3.50; N, 16.27. Found: C, 66.26; H, 3.46; N, 16.24.

1-(6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-3-phenyl-1H-pyrazole-4-carbaldehyde (10b)

Yield 3.00 g (71%); mp 190–192°C; IR: 3400–3100 (broad, medium, -NH- stretching), 1693 (strong, sharp, -CO- stretching), 1659 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 7.11–8.32 (m, 7H, Ar-H), 8.62 (s, 1H, -CH, α-proton to the enamine nitrogen), 9.12 (s, 1H, -CHO), 9.30 (s, 1H, pyrazole -CH), 11.10 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 424 [M+H]+. Anal. Calcd for C19H11BrN4O3: C, 53.92; H, 2.62; N, 13.24. Found: C, 53.90; H, 2.60; N, 13.22.

3-(Chloro-phenyl)-1-(4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-3-phenyl-1H-pyrazole-4-carbaldehyde (10c)

Yield 2.64 g (70%); mp 198–200°C; IR: 3300–3200 (broad, medium, -NH- stretching), 1695 (strong, sharp, -CO- stretching), 1665 cm-1 (strong, sharp, due to -CO- stretching); 1H NMR: δ 7.20–8.45 (m, 7H, Ar-H), 8.72 (s, 1H, -CH, α-proton to the enamine nitrogen), 9.10 (s, 1H, -CHO), 9.25 (s, 1H, pyrazole -CH), 11.25 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 379 [M+H]+. Anal. Calcd for C19H11ClN4O3: C, 60.25; H, 2.93; N, 14.79. Found: C, 60.21; H, 2.90; N, 14.76.

1-(6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-3-(4-chloro-phenyl)-1H-pyrazole-4-carbaldehyde (10d)

Yield 3.29 g (72%); mp 204–206°C; IR: 3400–2900 (broad, medium, -NH- stretching), 1692 (strong, sharp, -CO- stretching), 1670 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 7.26–8.30 (m, 6H, Ar-H), 8.72 (s, 1H, -CH, α-proton to the enamine nitrogen), 9.15 (s, 1H, -CHO), 9.27 (s, 1H, pyrazole -CH), 11.55 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 458 [M+H]+. Anal. Calcd for C19H10ClBrN4O3: C, 49.86; H, 2.20; N, 12.24. Found: C, 49.84; H, 2.18; N, 12. 22.

3-(Nitro-phenyl)-1-(4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-3-phenyl-1H-pyrazole-4-carbaldehyde (10e)

Yield 2.91 g (75%); mp 212–214°C; IR: 3400–3000 (broad, medium, -NH- stretching), 1698 (strong, sharp, -CO- stretching), 1669 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 7.23–8.40 (m, 7H, Ar-H), 8.68 (s, 1H, -CH, α-proton to the enamine nitrogen), 9.10 (s, 1H, -CHO), 9.25 (s, 1H, pyrazole-CH), 10.50 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 390 [M+H]+. Anal. Calcd for C19H11N5O5: C, 58.62; H, 2.85; N, 17.99. Found: C, 58.60; H, 2.81; N, 17.96.

1-(6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-3-(4-nitro-phenyl)-1H-pyrazole-4-carbaldehyde (10f)

Yield 3.65 g (78%); mp 218–220°C; IR: 3200–3100 (broad, medium, -NH- stretching), 1698 (strong, sharp, -CO- stretching), 1676 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 7.13–8.30 (m, 6H, Ar-H) 8.79 (s, 1H, -CH, α-proton to the enamine nitrogen), 9.10 (s, 1H, -CHO), 9.28 (s, 1H, pyrazole-CH), 11.95 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 469 [M+H]+. Anal. Calcd for C19H10BrN5O5: C, 48.74; H, 2.15; N, 14.96. Found: C, 48.73; H, 2.13; N, 14.95.

3-(Methyl-phenyl)-1-(4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-3-phenyl-1H-pyrazole-4-carbaldehyde (10g)

Yield 2.68 g (75%); mp 186–188°C; IR: 3400–3100 (broad, medium, -NH- stretching), 1698 (strong, sharp, -CO- stretching), 1675 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 2.45 (s, 3H, -CH3), 7.25–8.35 (m, 7H, Ar-H), 8.54 (s, 1H, -CH, α-proton to the enamine nitrogen), 9.16 (s, 1H, -CHO), 9.42 (s, 1H, pyrazole-CH), 12.00 (sharp, s, 1H, -NH, D2O exchangeable); M: m/z 359 [M+H]+. Anal. Calcd for C20H14N4O3: C, 67.03; H, 3.94; N, 15. 63. Found: C, 67.00; H, 3.90, N, 15.60.

1-(6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-3-(4-methyl-phenyl)-1H-pyrazole-4-carbaldehyde (10h)

Yield 3.05 g (70%); mp 194–196°C; IR: 3100–2900 (broad, medium, -NH- stretching), 1710 (strong, sharp, -CO- stretching), 1686 cm-1 (strong, sharp, -CO- stretching); 1H NMR: δ 2.70 (s, 3H, -CH3), 7.30–8.14 (m, 6H, Ar-H), 8.60 (s, 1H, -CH, α-proton to the enamine nitrogen), 9.20 (s, 1H, -CHO), 9.35 (s, 1H, pyrazole-CH), 11.20 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 438 [M+H]+. Anal. Calcd for C20H13BrN4O3: C, 54.94; H, 3.00; N, 12.81. Found: C, 54.90; H, 2.97; N, 12.80.

3-(Methoxy-phenyl)-1-(4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-3-phenyl-1H-pyrazole-4-carbaldehyde (10i)

Yield 2. 61 g (70%); mp 166–168°C; IR: 3430–3100 (broad, medium, -NH- stretching), 1697 (strong, sharp, -CO- stretching), 1655 cm-1 (strong, sharp, -CO-); 1H NMR (DMSO d6/TMS): δ 3.15 (s, 3H, -OCH3), 7.27–8.11 (m, 7H, Ar-H), 8.54 (s, 1H, -CH, α-proton to the enamine nitrogen), 9.26 (s, 1H, -CHO), 9.28 (s, 1H, pyrazole-CH), 11.55 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 375 [M+H]+. Anal. Calcd for C20H14N4O4: C, 64.14; H, 3.77; N, 14.97. Found: C, 64.10; H, 3.75; N, 14.94.

1-(6-Bromo-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-3-(4-methoxy-phenyl)-1H-pyrazole-4-carbaldehyde (10j)

Yield 3.34 g (75%); mp 175–177°C; IR: 3430–3100 (broad, medium, -NH- stretching), 1698 (strong, sharp, due to -CO- stretching), 1666 cm-1 (strong, sharp, due to -CO- stretching); 1H NMR: δ 3.20 (s, 3H, -OCH3), 7.45–8.24 (m, 6H, Ar-H), 8.58 (s, 1H, -CH, α-proton to the enamine nitrogen), 9.21 (s, 1H, -CHO), 9.30 (s, 1H, pyrazole-CH), 11.35 (sharp, s, 1H, -NH, D2O exchangeable); MS: m/z 454 [M+H]+. Anal. Calcd for C20H13BrN4O4: C, 53.00; H, 2.89; N, 12.36. Found: C, 52.97; H, 2.86; N, 12.31.

Preparation of 7 from 10

A mixture of 10a (10 mmol), iodine (5 mmol), (diacetoxyiodo)benzene (15 mmol), and ethanol (25 mL) was stirred for 12 h, then poured onto crushed ice (25 mL) and extracted with CHCl3 (2×10 mL). The organic extract was dried over anhydrous Na2SO4, concentrated, and the residue of 7e crystallized from ethanol.

Corresponding author: Muggu V.S.R.K. Chaitanya, Department of Chemistry, Jawaharlal Nehru Technological University, Hyderabad College of Engineering, Kukatpally, 500 085 Hyderabad (A.P.), India

The authors are thankful to the University Grants Commission, Government of India, New Delhi, for giving financial support and to the authorities of Jawaharlal Nehru Technological University Hyderabad for providing laboratory facilities.

References

[1] Amir, Md.; Alam Khan, S.; Khan, M. Synthesis and antibacterial activity of some new 1-substituted 3,5-diphenyl-4-(arylazo) pyrazoles. Indian J. Heterocycl. Chem. 2001, 11, 55–58.Search in Google Scholar

[2] Jain, R.; Pandya, P.; Bhadauria, J.; Tomar, S. Synthesis of some potential anti-bacterial pyrazole and pyrazolones. J. Indian Chem. Soc. 2000, 77, 42–43.Search in Google Scholar

[3] Elvin, L. A.; John, E. C.; Leon, C. G.; John, J. L.; Harry, E. R. Synthesis and muscle relaxant properties of 3-amino-4-arylpyrazoles. J. Med. Chem. 1964, 7, 259–268.Search in Google Scholar

[4] Pruit, J. R.; Pinto, D. J. P.; Galemmo, R. A.; Alexander, R. S.; Rossi, K. A.; Wells, B. L.; Drummond, S.; Bostrom, L. L.; Burdick, D.; Bruckner, R.; et al. Discovery of 1-(2-aminomethylphenyl)-3-trifluoromethyl-N-[3-fluoro-21-(aminosulfonyl) [1,11-biphenyl]4-yl]-1H-pyrazol-5-carboxyamide (DPC602), a potent, selective and orally bio-available factor. J. Med. Chem. 2003, 46, 5298–5305.Search in Google Scholar

[5] Gupta, D.P.; Bhadauria, R. S.; Soan, V. Synthesis of anti-microbial activity of N-substituted pyrazole derivatives. Int. J. Pharm. Appl. Sci. 2010, 1, 97–99.Search in Google Scholar

[6] Makhsumov, A. D.; Dzhurae, K. G.; Nikbae, A. T. Anti-inflammatory activity of some pyrazole derivatives. Pharm. Chem. J. 1986, 20, 289–291.Search in Google Scholar

[7] Manfredini, S.; Bazzanini, R.; Baraldi, P. G.; Guarneri, M.; Simoni, D.; Marongiu, M. E.; Pani, A.; Tramontano, E.; Colla, P.L. Pyrazole-related nucleosides. Synthesis and anti-viral/anti-tumor activity of some substituted pyrazole and pyraolo[4,3-d]-1,2,3-triazin4-one nucleosides. J. Med. Chem. 1992, 35, 917–924.Search in Google Scholar

[8] Kees, K. L. Jr.; Fitzgerald, J. J.; Steiner, J. F.; Mattes, B.; Mihan, T.; Tosi, D.; Mondoro, D.; McCaleb, M. L. New potent antihyperglycemic agents in db/db mice; synthesis and structure activity relationship studies of (4-substituted benzyl) trifluoromethyl) pyrazoles and pyrazolones. J. Med. Chem. 1996, 39, 3920–3928.Search in Google Scholar

[9] Terett, N. K.; Bell, A. S.; Brown, D.; Ellis, P. Sildenafil (VIAGRA™), a potent and selective inhibitor of type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction. Bioorg. Med. Chem. Lett. 1996, 6, 1819–1824.Search in Google Scholar

[10] Sahu, S. K.; Banarjee, M.; Samantray, A.; Behera, C.; Azam, M. A. Synthesis and antiviral evaluation of some new pyrazole and fused pyrazolopyrimidine derivatives. Trop. J. Pharm. Res. 2008, 7, 961–968.Search in Google Scholar

[11] Sin-Ru, S.; Tzu-Yum, C.; Reddy, G. R.; Sung-Nain, T.; Hsium-Ling, C.; Wen-Fang, T.; Ming-Sian, W. U.; Jiann-Yih, Y.; Nu-Sheng, C.; John, T. A. H.; et al. Pyrazole compound BPR1P0034 with potent and selective anti-influenza virus activity. J. Biomed. Sci. 2010, 17, 13–16.Search in Google Scholar

[12] Vernon, V. Y.; William, D.; Richard, E. I. International Minerals and Chemical Corp., 1980, US 4221791 (C1-424-248).Search in Google Scholar

[13] Cilnton, R. O.; Manson, A. J.; Stonner, F. W.; Neumann, H. C.; Christiansen, R. G.; Clarke, R. L.; Ackerman, J. H.; Page, D. F. Steroidal[3,2-C] pyrazoles. 11. Androstances, 19-norandrostances and their unsaturated analogs. J. Am. Chem. Soc. 1961, 83, 1478.Search in Google Scholar

[14] Chaitanya, M. V. S. R. K.; Dubey, P. K. Synthesis of novel naphthyridines as potential antibacterial agents. Indian J. Heterocycl. Chem. 2010, 20, 105–108.Search in Google Scholar

[15] Chaitanya, M. V. S. R. K.; Dubey, P. K. A facile and convenient synthesis of naphthyridinoyl pyrazoles. Indian J. Heterocycl. Chem. 2010, 20, 109–112.Search in Google Scholar

[16] Allen, C. F. H. The naphthyridines. Chem. Rev. 1950, 47, 275–305.Search in Google Scholar

[17] Gerald, R. L. Cyclization of 2-aminopyridine with substituted ethyl 2-malonates. J. Am. Chem. Soc. 1948, 70, 3348–3350.Search in Google Scholar

Received: 2012-6-19
Accepted: 2012-8-7
Published Online: 2013-01-18
Published in Print: 2013-03-01

©2013 by Walter de Gruyter Berlin Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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https://doi.org/10.1515/hc-2012-0097
Keywords for this article
(diacetoxyiodo)benzene; hydrazide; β-keto esters; naphthyridine; substituted acetophenone; Vilsmeier-Haack reagent
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Articles in the same Issue

  1. Masthead
  2. Masthead
  3. Reviews
  4. Synthesis and applications of benzothiazole containing cyanine dyes
  5. Synthesis and chemistry of structurally unique hexasubstituted pyrazolines
  6. Research Articles
  7. Synthesis and characterization of heteroarylthio derivatives of 5,17-di-tert-butyl-11,23-diamido-25, 27-diprotected calix[4]arene
  8. New heterocyclic chalcones. Part 6. Synthesis and cytotoxic activities of 5- or 6-(3-aryl- 2-propenoyl)-2(3H)-benzoxazolones
  9. Novel benzofuran derivatives: synthesis and antitumor activity
  10. Synthesis, characterization and in vitro antimicrobial assessment of some novel 4H-1, 4-benzothiazines and their sulfone derivatives
  11. Efficient synthesis, X-ray diffraction study and antimicrobial activity of some novel thiazolidin-4-ones and perhydro-1,3-thiazin-4-ones
  12. A simple and efficient synthesis of novel naphthyridine-1-H-pyrazole-4-carboxylic acid esters/carbaldehydes using Vilsmeier-Haack reagent
  13. Melamine-formaldehyde resin supported H+-catalyzed three-component synthesis of 1,8-dioxo-decahydroacridine derivatives in water and under solvent-free conditions
  14. A simple and efficient procedure for synthesis of symmetrical bis(4-amino-4H-1,2,4-triazole-5-thiols)
  15. Poly(ethylene)glycol/AlCl3 as a new and efficient system for multicomponent Biginelli-type synthesis of pyrimidinone derivatives
  16. Synthesis, crystal structure, and bioactivity of N-dichloroacetyl diazabicyclo compounds
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