Synthesis of N,N’-Diarylalkanediamides and Their Antimycobacterial and Antialgal Activity
Abstract
:Introduction
Results and Discussion
Experimental
General
Synthesis of alkanedioyl dichlorides
Butanedioyl dichloride
Octanedioyl dichloride
Synthesis of N,N’-diarylalkanediamides
N,N’-Diarylethanediamides (1-4)
Other N,N’-diarylalkanediamides (5-46)
Biological assays
Antimycobacterial activity
Antialgal activity
Acknowledgements
References and Notes
- Waisser, K.; Odlerova, Z.; Grunert, R. Antituberkulotika. 43. Mitteilung. Eine neue gruppe potentieller Antituberkulotika - Oxalanilide und Malonanilide. Pharmazie 1989, 44, 162–163. [Google Scholar] [PubMed]
- Dave, M. P.; Patel, J. M.; Langalia, N. A.; Shah, S. R.; Thaker, K. A. Studies on synthesis and antitubercular activity of some (±)-α-aceto-N,N’-diarylsuccinamide. J. Indian Chem. Soc. 1985, 62, 386–387. [Google Scholar]
- Al-Arab, M. M.; Na'was, T. E.; Abu-Yousef, I. A. Synthesis of 2,3-diarylglutaramides and their antibacterial activity. Indian J. Chem. 1990, 29B, 694–696. [Google Scholar]
- Stauffer Chemical Co.: Ger. Offen. 24 51 512 (1975).
- Raynes, K.; Galatis, D.; Cowman, A. F.; Tilley, L.; Deady, L. W. Synthesis and activity of some antimalarial bisquinolines. J. Med. Chem. 1995, 38, 204–206. [Google Scholar] [CrossRef] [PubMed]
- Kubicova, L.; Kadlcikova, J.; Waisser, K.; Kralova, K.; Sersen, F.; Slosarek, M.; Janota, J.; Svoboda, Z. Succinanilides and their photosynthesis-inhibiting and antimycobacterial activity. Folia Pharm. Univ. Carol. 1998, 23 (Suppl.), 148–149. [Google Scholar]
- Kubicova, L.; Kralova, K.; Kunes, J.; Waisser, K. Synthesis of some N,N'-diphenylalkanediamides and their photosynthesis-inhibiting activity. Chem. Papers 2000, 54, 90–93. [Google Scholar]
- Lapkin, I. I.; Andreichikov, Ju. S. Esters of heteroacids of the acetylene series. I. Addition of primary amines to esters of phenylethynylglyoxalic acid. Zh. Org. Khim. 1965, 1, 1212–1214. [Google Scholar]
- Price, Ch. C.; Velzen, B. H. Some derivatives of oxanilide. J. Org. Chem. 1947, 12, 386–392. [Google Scholar] [CrossRef] [PubMed]
- CIBA-GEIGY A.-G.: U. S. 3906033 (1975); Chem. Abstr. 1976, 84, 4633 r.
- Barnicoat, C. R. Melting points of the substituted amides of dibasic acids. J. Chem. Soc. 1927, 2926–2929. [Google Scholar] [CrossRef]
- Kirshanov, A. V.; Egorova, A. N. L. Fenilamidirovanie dvuchosnovnych karbonovych kislot difenilamidom. Zh. Obsch. Khim. 1953, 23, 1920–1922. [Google Scholar]
- Ueda, M.; Morishima, M.; Kakuta, U.; Sugiyama, Y. Synthesis of ordered polyamides by direct polycondensation. Macromolecules 1992, 25, 6580–6585. [Google Scholar] [CrossRef]
- Sanna, A.; Repetto, G. Preparation of halodiphenylsuccinamides. Gazz. Chim. Ital. 1927, 57, 777–780. [Google Scholar]
- Chen-Ku, L.; Chang-Shih, T.; Chi-Chieh, Ch. Synthesis of α,ω-bis(p-alkoxyphenylamino)alkanes and N,N’-bis(p-substituted phenyl)alkanedicarboxamides. Yao Hsueh Hsueh Pao 1957, 5, 333–339, (ref. Chem. Abstr. 1961, 55, 25862i). [Google Scholar]
- Hill, J. W.; Wallace, H. C. Studies of polymerization and ring formation. J. Amer. Chem. Soc. 1933, 55, 5023–5031. [Google Scholar] [CrossRef]
- Vorlaender, D. Über Aethylenester zweibasischer Säuren und Phenole. Justus Liebigs Ann. Chem. 1894, 280, 167–206. [Google Scholar] [CrossRef]
- Auwers, K.; Schmidt, M. Über die Konstitution der Chloride von 1,2- und 1,3-Dicarbonsäuren. Chem. Ber. 1913, 46, 457–487. [Google Scholar] [CrossRef]
- Hoffmann, H. M. R.; Haase, K.; Geschwinder, P. M. The synthesis of aliphatic dicarboxylic acid diiodides and aromatic analogues. Synthesis 1982, 3, 237–239. [Google Scholar] [CrossRef]
- Hollingsworth, B. L.; Petrow, V. Some α,ω-di(phenanthridin-6-yl)alkanes. J. Chem. Soc. 1961, 3664–3667. [Google Scholar] [CrossRef]
- Kralova, K.; Sersen, F.; Melnik, M. Inhibition of photosynthesis in Chlorella vulgaris by Cu(II) complexes with biologically active ligands. J. Trace Microprobe Techn. 1998, 16, 491–500. [Google Scholar]
- Inskeep, W. P.; Bloom, P. R. Extinction coefficients of chlorophyll a and b in N,N-dimethylformamide and 80% acetone. Plant. Physiol. 1985, 77, 483–485. [Google Scholar] [CrossRef] [PubMed]
- Samples Availability: available from the authors.
Compd. | Formula (M. w.) | m | R | M.p. (°C) (Yield, %) | % Calc. % Found | ||
C | H | N | |||||
1a | C16H16N2O2 | 0 | 2-CH3 | 211-212 | - | - | - |
(268.3) | (65) | ||||||
2a | C16H16N2O2 | 0 | 3-CH3 | 135-137 | - | - | - |
(268.3) | (60) | ||||||
3a | C14H10N4O6 | 0 | 4-NO2 | 357-358 | - | - | - |
(330.3) | (61) | ||||||
4a | C14H10Br2N2O2 | 0 | 4-Br | 329-331 | - | - | - |
(398.1) | (58) | ||||||
5a | C16H14Br2N2O2 | 2 | 4-Br | 281-282 | - | - | - |
(426.1) | (92) | ||||||
6b | C16H12Cl4N2O2 | 2 | 3,4-Cl2 | 258-259 | - | - | - |
(406.1) | (93) | ||||||
7a | C16H16N2O2 | 2 | H | 231-233 | - | - | - |
(268.3) | (95) | ||||||
8a | C18H20N2O4 | 2 | 4-OCH3 | 256-257 | - | - | - |
(328.4) | (90) | ||||||
9 | C16H14Cl2N2O2 | 2 | 4-Cl | 288-290 | 56.99 | 4.18 | 8.31 |
(337.2) | (90) | 57.24 | 4.15 | 8.38 | |||
10 | C18H20N2O2 | 2 | 4-CH3 | 273-275 | 72.95 | 6.80 | 9.45 |
(296.4) | (91) | 72.87 | 6.79 | 9.59 | |||
11b | C16H14F2N2O2 | 2 | 3-F | 206-207 | - | - | - |
(304.3) | (89) | ||||||
12b | C16H14F2N2O2 | 2 | 4-F | 244-245 | - | - | - |
(304.3) | (92) | ||||||
13b | C16H14N4O6 | 2 | 3-NO2 | 228-230 | - | - | - |
(358.3) | (88) | ||||||
14b | C20H24N2O2 | 2 | 3,4-(CH3)2 | 231-232 | - | - | - |
(324.4) | (85) | ||||||
15a | C16H14Cl2N2O2 | 2 | 3-Cl | 233-235 | - | - | - |
(337.2) | (92) | ||||||
16b | C24H32N2O2 | 2 | 4-C4H9 | 232-234 | - | - | - |
(380.5) | (81) | ||||||
17b | C22H28N2O2 | 2 | 4-isoC3H7 | 234-236 | - | - | - |
(352.5) | (83) | ||||||
18b | C24H32N2O2 | 2 | 4-sec-C4H9 | 178-179 | - | - | - |
(380.5) | (81) | ||||||
19a | C20H26N4O2 | 2 | 4-N(CH3)2 | 282.5-283.5 | - | - | - |
(354.5) | (88) | ||||||
20 | C18H14N4O2S2 | 2 | c | 282-285 | 56.53 | 3.69 | 14.65 |
(382.5) | (92) | 56.55 | 3.87 | 14.88 | |||
21 | C17H16Cl2N2O2 | 3 | 4-Cl | 242-243 | 58.13 | 4.59 | 7.98 |
(351.2) | (70) | 58.13 | 4.59 | 7.98 | |||
22 | C19H22N2O4 | 3 | 4-OCH3 | 222.5-224 | 66.65 | 6.48 | 8.18 |
(342.4) | (62) | 66.93 | 6.45 | 8.24 | |||
23a | C17H18N2O2 | 3 | H | 224-225 | - | - | - |
(282.3) | (84) | ||||||
24a | C19H22N2O2 | 3 | 4-CH3 | 220-2211 | - | - | - |
(310.4) | (54) | ||||||
25b | C17H14Cl4N2O2 | 3 | 3,4-Cl2 | 266-267 | - | - | - |
(420.1) | (63) | ||||||
26a | C17H16Br2N2O2 | 3 | 4-Br | 256-257 | - | - | - |
(440.1) | (58) | ||||||
27 | C20H24N2O2 | 4 | 4-CH3 | 258-259 | 74.05 | 7.46 | 8.63 |
(324.4) | (67) | 74.21 | 7.52 | 8.66 | |||
28a | C18H20N2O2 | 4 | H | 237-238 | - | - | - |
(296.4) | (75) | ||||||
29 | C18H18N4O6 | 4 | 3-NO2 | 238-239 | 55.96 | 4.70 | 14.50 |
(386.4) | (58) | 55.80 | 4.73 | 14.67 | |||
30 | C18H18Cl2N2O2 | 4 | 3-Cl | 197-198 | 59.19 | 4.97 | 7.67 |
(365.3) | (60) | 59.14 | 4.97 | 7.90 | |||
31b | C18H16Cl4N2O2 | 4 | 3,4-Cl2 | 276-277 | - | - | - |
(434.2) | (59) | ||||||
32 | C20H24N2O4 | 4 | 2-OCH3 | 151-152 | 67.40 | 6.79 | 7.86 |
(356.4) | (40) | 67.49 | 6.68 | 7.79 | |||
33 | C20H24N2O4 | 4 | 4-OCH3 | 233-234 | 67.40 | ||
(356.4) | (65) | 67.62 | 6.78 | 7.88 | |||
34 | C18H18Cl2N2O2 | 4 | 4-Cl | 238-239 | 59.19 | 4.97 | 7.67 |
(356.3) | (67) | 58.91 | 4.82 | 7.79 | |||
35 | C24H28N2O6 | 4 | 4-COOC2H5 | 216-217 | 65.44 | 6.41 | 6.36 |
(440.5) | (54) | 65.70 | 6.33 | 6.17 | |||
36b | C20H20Cl4N2O2 | 6 | 3,4-Cl2 | 167-168 | - | - | - |
(462.2) | (35) | ||||||
37 | C20H22Cl2N2O2 | 6 | 4-Cl | 197-198 | 61.11 | 5.60 | 7.12 |
(393.3) | (81) | 61.08 | 5.64 | 7.12 | |||
38a | C20H24N2O2 | 6 | H | 186-188 | - | - | - |
(324.4) | (57) | ||||||
39a | C22H28N2O2 | 6 | 4-CH3 | 224-226 | - | - | - |
(352.5) | (55) | ||||||
40 | C22H28N2O4 | 6 | 4-OCH3 | 220-221 | 68.78 | 7.24 | 7.29 |
(384.5) | (63) | 68.60 | 7.15 | 7.19 | |||
41a | C20H22Br2N2O2 | 6 | 4-Br | 251-253 | - | - | - |
(482.2) | (54) | ||||||
42b | C21H22Cl4N2O2 | 7 | 3,4-Cl2 | 170-171 | - | - | - |
(476.2) | (52) | ||||||
43 | C21H24Cl2N2O2 | 7 | 4-Cl | 196-197 | 61.92 | 5.94 | 6.88 |
(407.3) | (61) | 62.06 | 5.85 | 6.99 | |||
44a | C21H26N2O2 | 7 | H | 180-181 | - | - | - |
(338.5) | (63) | ||||||
45a | C23H30N2O2 | 7 | 4-CH3 | 197-198 | - | - | - |
(366.5) | (61) | ||||||
46 | C23H30N2O4 | 7 | 4-OCH3 | 194-196 | 69.32 | 7.59 | 7.03 |
(398.5) | (44) | 69.61 | 7.73 | 7.07 |
Compd. | 1H NMR δ (ppm) | IR ν(C=O) (cm-1) |
1 | - | 1668 |
2 | - | 1666 |
3 | - | 1706 |
4 | - | 1666 |
5 | - | 1652 |
6 | - | 1659 |
7 | - | 1663 |
8 | - | 1648 |
9 | 2.63 (s, 4H), 7.35-7.28 (m, 4H) , 7.63-7.56 (m, 4H), 10.14 (s, 2H) | 1652 |
10 | 2.21 (s, 6H), 2.60 (s, 4H), 7.11-7.03 (m, 4H) , 7.48-7.40 (m, 4H), 9.89 (s, 2H) | 1655 |
11 | - | 1663 |
12 | - | 1651 |
13 | - | 1675 |
14 | - | 1651 |
15 | - | 1668 |
16 | - | 1659 |
17 | - | 1656 |
18 | - | 1655 |
19 | - | 1645 |
20 | 2.88 (s, 4H), 7.32-7.23 (m, 2H) , 7.46-7.37 (m, 2H), 7.76-7.69 (m, 2H), 7.97-7.90 (m, 2H) | 1694 |
21 | 1.95-1.81 (m, 2H), 2.36 (t, J=7.4 Hz, 4H), 7.35-7.29 (m, 4H) , 7.64-7.57 (m, 4H), 10.05 (s, 2H) | 1664 |
22 | 1.93-1.81 (m, 2H), 2.31 (t, J=7.4 Hz, 4H), 3.69 (s, 6H), 6.89-6.79 (m, 4H) , 7.53-7.43 (m, 4H), 9.76 (s, 2H) | 1659 |
23 | - | 1673 |
24 | - | 1664 |
25 | - | 1679 |
26 | - | 1664 |
27 | 1.63-1.55 (m, 4H),2.21 (s, 6H), 2.33-2.24 (m, 4H), 7.10-7.03 (m, 4H) , 7.48-7.41 (m, 4H), 9.79 (s, 2H) | 1659 |
28 | - | 1660 |
29 | 1.70-1.60 (m, 4H), 2.43-2.33 (m, 4H), 7.57 (t, J=8.1, 2H), 7.91-7.83 (m, 4H), 8.63 (t, J=2.1 Hz, 2H), 10.41 (s, 2H) | 1667 |
30 | 1.65-1.55 (m, 4H), 2.38-2.27 (m, 4H), 7.10-7.03 (m, 2H) , 7.30 (t, J=8.1, 2H), 7.45-7.38 (m, 2H), 7.80 (t, J=1.9, 2H), 10.09 (s, 2H) | 1663 |
31 | - | 1670 |
32 | 1.65-1.54 (m, 4H), 2.44-2.33 (m, 4H), 3.79 (s, 6H), 6.93-6.82 (m, 2H), 7.10-6.96 (m, 4H), 7.97-7.84 (m, 2H), 9.03 (s, 2H) | 1659 |
33 | 1.64-1.52 (m, 4H), 2.33-2.20 (m, 4H), 3.69 (s, 6H), 6.89-6.79 (m, 4H), 7.52-7.42 (m, 4H), 9.74 (s, 2H) | 1648 |
34 | 1.65-1.55 (m, 4H), 2.37-2.26 (m, 4H), 7.35-7.29 (m, 4H), 7.63-7.56 (m, 4H), 10.03 (s, 2H) | 1656 |
35 | 1.28 (t, J=7.1 Hz, 6H), 1.68-1.57 (m, 4H), 2.42-2.31 (m, 4H), 4.25 (q, J=14.2, J=7.1 Hz, 4H), 7.74-7.67 (m, 4H), 7.91-7.84 (m, 4H), 10.25 (s, 2H) | 1708, 1693 |
36 | - | 1671 |
37 | 1.36-1.25 (m, 4H), 1.64-1.49 (m, 4H), 2.27 (t, J=7.4, 4H), 7.35-7.27 (m, 4H), 7.63-7.55 (m, 4H), 10.00 (s, 2H) | 1659 |
38 | - | 1659 |
39 | - | 1656 |
40 | 1.34-1.24 (m, 4H), 1.64-1.48 (m, 4H), 2.24 (t, J=7.4, 4H), 3.68 (s, 6H), 6.87-6.79 (m, 4H), 7.50-7.42 (m, 4H), 9.72 (s, 2H) | 1652 |
41 | - | 1664 |
42 | - | 1680 |
43 | 1.32-1.22 (m, 6H), 1.63-1.48 (m, 4H), 2.27 (t, J=7.3 Hz, 4H), 7.34-7.28 (m, 4H), 7.62-7.55 (m, 4H), 10.00 (s, 2H) | 1660 |
44 | - | 1671 |
45 | - | 1662 |
46 | 1.35-1.20 (m, 6H), 1.63-1.47 (m, 4H), 2.23 (t, J=7.3 Hz, 4H), 3.68 (s, 6H), 6.88-6.80 (m, 4H), 7.50-7.42 (m, 4H), 9.71 (s, 2H) | 1655 |
Compound | m | R | MIC (μmol dm-3) | |||
M. tuberculosis | M. avium | M. kansasii | M. fortuitum | |||
3 | 0 | 4-NO2 | 37 | -a) | -a) | -a) |
4 | 0 | 4-Br | 4.1 | -a) | -a) | -a) |
6 | 2 | 3,4-Cl2 | 250 | 250 | 500 | 500 |
7 | 2 | H | 500 | 500 | 500 | 500 |
12 | 2 | 4-F | 250 | 1000 | 1000 | 1000 |
14 | 2 | 3,4-(CH3)2 | 500 | >1000 | >1000 | >1000 |
15 | 2 | 3-Cl | 500 | >1000 | >1000 | >1000 |
16 | 2 | 4-C4H9 | 500 | 63 | >1000 | >1000 |
17 | 2 | 4-isoC3H7 | >1000 | 63 | >1000 | >1000 |
18 | 2 | 4-sec-C4H9 | 500 | 63 | >1000 | >1000 |
m | Compound % of inhibition | ||||
R= H | 4-CH3 | 4-OCH3 | 4-Cl | 3,4-Cl2 | |
2 | 7 | 10 | 8 | 9 | 6 |
22.8 | 14.2 | 30.8 | 33.2 | 19.8 | |
3 | 23 | 24 | 22 | 21 | 25 |
41.8 | 26.2 | 41.6 | 34.3 | 28.7 | |
4 | 28 | 27 | 33 | 34 | 31 |
41.0 | 37.7 | 46.0 | 41.4 | 33.5 | |
6 | 38 | 39 | 40 | 37 | 36 |
44.2 | 41.4 | 57.9 | 45.4 | 22.6 | |
7 | 44 | 45 | 46 | 43 | 42 |
48.5 | 37.9 | 53.9 | 45.5 | 15.1 |
Compound | R | % of inhibition | Compound | R | % of inhibition |
7 | H | 22.8 | 5 | 4-Br | 27.1 |
11 | 3-F | 25.2 | 17 | 4-isoC3H7 | 36.5 |
15 | 3-Cl | 43.6 | 16 | 4-C4H9 | 32.6 |
13 | 3-NO2 | 25.4 | 18 | 4-sec-C4H9 | 36.5 |
12 | 4-F | 35.4 | 19 | 4-N(CH3)2 | 28.8 |
9 | 4-Cl | 33.2 | 6 | 3,4-Cl2 | 19.8 |
10 | 4-CH3 | 14.2 | 14 | 3,4-(CH3)2 | 26.7 |
8 | 4-OCH3 | 30.8 |
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Kubicova, L.; Waisser, K.; Kunes, J.; Kralova, K.; Odlerova, Z.; Slosarek, M.; Janota, J.; Svoboda, Z. Synthesis of N,N’-Diarylalkanediamides and Their Antimycobacterial and Antialgal Activity. Molecules 2000, 5, 714-726. https://doi.org/10.3390/50500714
Kubicova L, Waisser K, Kunes J, Kralova K, Odlerova Z, Slosarek M, Janota J, Svoboda Z. Synthesis of N,N’-Diarylalkanediamides and Their Antimycobacterial and Antialgal Activity. Molecules. 2000; 5(5):714-726. https://doi.org/10.3390/50500714
Chicago/Turabian StyleKubicova, Lenka, Karel Waisser, Jiri Kunes, Katarina Kralova, Zelmira Odlerova, Milan Slosarek, Jiri Janota, and Zbynek Svoboda. 2000. "Synthesis of N,N’-Diarylalkanediamides and Their Antimycobacterial and Antialgal Activity" Molecules 5, no. 5: 714-726. https://doi.org/10.3390/50500714