Heteroaromatic tosylates and phosphates are suitable electrophiles in iron-catalyzed cross-coupling reactions with alkyl Grignard reagents. These reactions are performed at low temperature allowing good functional group tolerance with full conversion within minutes. Lindhardt, T. Skrydstrup, Org. The success of a one-step transformation of heterocyclic N -oxides to 2-alkyl-, aryl-, and alkenyl-substituted N -heterocycles hinges on the combination of copper catalysis and activation by lithium fluoride or magnesium chloride. The utility for the scaffold decoration of a broad range of complex N -heterocycles is exemplified by syntheses of new structural analogues of several antimalarial, antimicrobial, and fungicidal agents.
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Quinolines, an important class of potentially bioactive compounds, have been synthesized by treatment of o-aminoaryl ketones and carbonyl compound utilizing niobium V chloride NbCl 5 as an available and inexpensive catalyst.
Not only diketones but also ketones afforded the desired products in good to excellent yields. The reaction time of 2-aminochlorobenzophenone and dicarbonyl compounds was longer than that of 2-aminobenzophenone. The reaction of cyclic diketones took place faster than open chain analogues. These reactions also proceeded with acetophenone derivatives.
In these cases the reaction times are longer. The synthesis of quinolines has been of considerable interest to chemists because their oxygen heterocycles may contribute to potential antimalarial, antibacterial, antiasthmatic, antihypertensive, anti-inflammatory, and antiplatelet properties [ 1 — 3 ]. For the synthesis of quinolines, various methods have been reported including the Skraup [ 4 ], Conrad-Limpach-Knorr [ 5 ], Pfitzinger [ 6 ], Friedlander [ 7 ], and Combes [ 8 ].
However, the Friedlander condensation is still considered as a popular method for the synthesis of quinoline derivatives [ 9 — 14 ]. Solvents are chemical substances used in huge amounts for many different applications. One of the key areas of Green Chemistry is the elimination of solvents in chemical processes or the replacement of hazardous solvents with environmentally benign solvents. Glycerol, which is a nontoxic, biodegradable liquid manufactured from renewable sources, shows similar properties as an ionic liquid and has a high potential to serve as green solvent for organic syntheses.
It has a very high boiling point and negligible vapor pressure; it is compatible with most organic and inorganic compounds and does not require special handling or storage. Glycerol permits turning to the advantages of both water low toxicity, low price, large availability, and renewability and ionic liquids high boiling point, low vapour pressure [ 15 ].
Nevertheless the development of new synthetic methods for the efficient preparation of heterocycles containing quinoline fragment is therefore an interesting challenge.
Therefore, in this report we describe synthesis of quinoline derivatives by treatment of 2-aminobenzophenone with various carbonyl compounds using NbCl 5 as available catalysts in glycerol with high yields.
Carbonyl compounds and -aminobenzophenone were purchased from Merck Chemical Company. Melting points were determined in electrothermal system open capillaries. NbCl 5 0. The progress of the reaction was monitored by thin layer chromatography. After complete reaction, the mixture was quenched by the addition of saturated aq NaHCO 3 solution and the reaction mixture was filtered and washed with ethanol. Due to the pharmacological properties of quinolines, development of synthetic methods, enabling easy access to these compounds, is desirable.
Therefore, in this paper we report synthesis of quinoline derivatives in the presence of niobium v chloride as an inexpensive and available catalyst. In order to evaluate the catalytic efficiency of NbCl 5 and to determine the most appropriate reaction conditions, initially a model study was carried out on the synthesis of quinoline 3 Scheme 1 by the condensation of 2-aminobenzophenone 1 and 1,3-cyclohexadione 2 in different sets of reaction conditions.
In preliminary experiment, this reaction was carried out in various solvents, with NbCl 5 0. The reaction proceeded perfectly in polar solvents Table 1 , entries 7 — 16 , but the yields decreased when the reaction was carried out in low-polar solvents Table 1 , entries 3 — 6.
The reaction could be carried out under solvent-free condition and gave low yield Table 1 , entries 1 , 2. To obtain the optimized reaction conditions, we also changed temperature and the amount of catalyst. The results are summarized in Table 2. Consequently, among the tested temperature and the amount of catalyst, the condensation of 2-aminobenzophenone and 1,3-cyclohexadione was best catalyzed by 0.
It is delighted that the reaction time of 1,3-diphenyl propane-1,3-dione was longer than that of acetylacetone, which is probably due to low reactivity of carbonyl groups. Also, the reaction time of 2-aminochlorobenzophenone and dicarbonyl compounds was longer than that of 2-aminobenzophenone. These reactions also proceeded with acetophenone derivatives Table 3 , entries 18 — It may be due to the less activity of acetophenone derivatives than dicarbonyl compounds.
All the aforementioned reactions Table 3 delivered good product yields and accommodated a wide range of aromatic carbonyl compound bearing both electron-donating and electron-withdrawing substituents. The reactivity of different aromatic carbonyl compounds was influenced by the nature and position of the substituents on the aromatic ring. The aromatic carbonyl derivatives having an electron-donating substituent were highly reactive and gave the products in excellent yields entries 19 — When the aromatic carbonyl compounds containing electron-withdrawing group were used, the reaction yield was decreased entries 22 , In conclusion, efficient synthesis of quinoline derivatives has been achieved by a one-pot coupling reaction of carbonyl compounds and -aminobenzophenone using catalytic amounts of NbCl 5 in glycerol.
Simple reaction procedures, inexpensive catalysts, and single product formation make this an attractive protocol over the existing procedures. This protocol offers flexibility in tuning the molecular complexity and diversity.
The authors declare that there is no conflict of interests regarding the publication of this paper. The authors gratefully acknowledge the support of this work by the Birjand University Research Council. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
We will be providing unlimited waivers of publication charges for accepted articles related to COVID Sign up here as a reviewer to help fast-track new submissions. Academic Editor: Hongxing Dai. Received 30 Aug Revised 14 Dec Accepted 15 Dec Published 21 Jan Abstract Quinolines, an important class of potentially bioactive compounds, have been synthesized by treatment of o-aminoaryl ketones and carbonyl compound utilizing niobium V chloride NbCl 5 as an available and inexpensive catalyst.
Introduction The synthesis of quinolines has been of considerable interest to chemists because their oxygen heterocycles may contribute to potential antimalarial, antibacterial, antiasthmatic, antihypertensive, anti-inflammatory, and antiplatelet properties [ 1 — 3 ]. Experimental Carbonyl compounds and -aminobenzophenone were purchased from Merck Chemical Company. Results and Discussion Due to the pharmacological properties of quinolines, development of synthetic methods, enabling easy access to these compounds, is desirable.
Scheme 1. Table 1. Table 2. Effect of temperature and the amount catalyst on the synthesis of 2-quinoline derivatives via a condensation of 2-aminobenzophenone and 1,3-cyclohexadione in the presence of NbCl 5 in glycerol.
Table 3. Synthesis of quinolones by the NbCl 5 -catalyzed in glycerole a. Scheme 2. References M. Maguire, K. Sheets, K. McVety, A. Spada, and A. Malkov, M. Kabeshov, M. Bella et al. Shaban, M. Taha, and E. Yadav, R.
Kumbhar, and S. View at: Google Scholar N. Heindel, T. Brodof, and J. Roberts and E. Yadav, P. Rao, D. Sreenu et al. Wu, H. Xia, and K. Arcadi, M. Chiarini, S. View at: Google Scholar M. Zhu, W. Fu, C. Xun, and G. View at: Google Scholar S. Song, S. Cho, D. Park, T. Kwon, and S. Palimkar, S. Siddiqui, T. Daniel, R. Lahoti, and K. Wolfson, C.
November 3, by ViveChemistry. His other works were in the fields of natural products like the structure of alkaloids, synthesis of iso-quinolines etc. H2SO4 and an oxidizing agent like nitrobenzene. Other examples of oxidizing agents used are As2O5 Arsenic acid.
Skraup quinoline synthesis
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Skraup Synthesis of Quinolines
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Synthesis of quinolines
It has been found that recent modifications of the Skraup quinoline synthesis can be further improved as to yield and ease of operation by substituting acetylated amines for the free bases. If you have an individual subscription to this journal, or if you have purchased this article through Pay-Per-view , you can gain access by logging in with your username and password here:. Advanced Search. All Journals Journal. Sorry, you do not have access to this content. You have requested the following content: Canadian Journal of Research, , Vol.