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Review

2-Azidobenzaldehyde-Based [4+2] Annulation for the Synthesis of Quinoline Derivatives

by
Xiaofeng Zhang
1,2,*,†,
Miao Liu
1,3,†,
Weiqi Qiu
1,4 and
Wei Zhang
1,*
1
Center for Green Chemistry and Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125, USA
2
Department of Medicinal Chemistry, Cerevel Therapeutics, Cambridge, MA 02141, USA
3
Department of Mechanical Engineering, University of Wisconsin Milwaukee, Milwaukee, WI 53211, USA
4
Department of Chemistry, Boston College, 2609 Beacon Street, Chestnut Hill, MA 20467, USA
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Molecules 2024, 29(6), 1241; https://doi.org/10.3390/molecules29061241
Submission received: 14 February 2024 / Revised: 6 March 2024 / Accepted: 8 March 2024 / Published: 11 March 2024
(This article belongs to the Special Issue Advances in the Synthesis of Heterocyclic Compounds and Their Applications)
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Abstract

:
Quinoline is a privileged heterocyclic ring which can be found in many drug molecules and bioactive compounds. The development of synthetic methods for making quinoline derivatives continuously attracts the interest of organic and medicinal chemists. This paper highlights 2-azidobenzaldehyde-based [4+2] annulation for the synthesis of quinoline derivatives including fused and spiro-quinolines, quinoline-4-ols, 4-aminoquinolines, and related compounds.

1. Introduction

Quinoline is a privileged scaffold for bioactive molecules [1,2,3,4,5,6]. Shown in Figure 1 are some quinoline-containing drug molecules, including Mefloquine (antimalarial) [7,8,9,10], Brequinar (anticancer) [11,12,13], Pitavastatin (cholesterol-lowering) [14,15,16], Plaquenil (antimalarial) [17,18], Ciprofloxacin (antibacterial) [19,20,21], and Lenvatinib (anticancer) [22,23,24]. Other than these commercial drugs, a great number of quinoline derivatives have been reported or are under development as druggable molecules for anticancer [25,26], antibacterial [27,28,29], antifungal [30,31,32], antiviral [33,34,35,36], antimalarial [37,38,39], antioxidant [40,41,42], anti-inflammatory [43,44,45], CNS effect [46,47], cardiovascular, anticonvulsant, analgesic, and anthelmintic research [48,49,50,51].
The synthesis of quinolines has continuously attracted the interest of organic and medicinal chemists. Over the years, many methods including name reactions such as Skraup, Doebner–von Miller, Friedlander, Ptzinger, Conrad–Limpach, and Combes syntheses [52,53] have been developed for making quinolines. Alam and Patel have reviewed the general synthetic methods [54,55], which included new methods such as cascade reactions [56] and metal-free one-pot synthesis [57,58].
Shown in Scheme 1 are three general approaches to assembling the quinoline ring. (I) [3+3] Annulation. The early developed methods such as the Skraup, Doebner–von Miller, Conrad–Limpach, Gould–Jacobs, and Combes syntheses are in this category. The drawback of this approach is that it has a low regioselectivity for the synthesis of multi-substituted quinolines [52,54,57]. (II) [4+2] Annulation. There are two ways to put together the pyridine ring according to [4+2] annulation (II-a and II-b). The first one has low regioselectivity and a limited substrate scope [52,55,56]. The second one is more popular and uses readily available substrates to give products with a good regioselectivity. Reactions such as the Friedlander and Ptzinger reactions are in this category [52,53,54,55,58]. (III) Cyclization. In theory, there are four different ways to form the pyridine ring of quinolines (III-a to III-d) according to cyclization. But they have not been fully developed due to the difficult reaction process and the limited availability of the substrates [59,60].
Presented in this paper are azidobenzaldehyde-based [4+2] annulation reactions (II-b type) for the synthesis of substituted quinolines [61]. For example, [4+2] annulation could be accomplished using a direct Diels–Alder reaction or via sequential condensation and cyclization reactions. In addition to quinolines, versatile 2-azidobenzaldehydes 1 could be used for the synthesis of other heterocyclic rings such as indoles [62,63], 3,4-dihydroquinazolines [64,65], triazolobenzodiazepines [66], 2H-indazoles [67], benzoxazepinones [68], and quinolines. Meanwhile, 2-azidobenzaldehydes could be easily prepared from commercially available 2-halobenzaldehydes, 2-aminobenzaldehydes, and 2-nitrobenzaldehydes [62,64,66,67,68]. Over 30 papers on the 2-azidobenzaldehyde-based synthesis of quinolines could be found in the literature and are summarized in this paper.

2. Results

2.1. Synthesis of 4-Unsubstituted Quinolines

There are many 4-nonsubstituted quinoline drugs and drug candidates (Figure 2), such as Bedaquiline for the treatment of active tuberculosis [69,70], Indacaterol for the treatment of chronic obstructive pulmonary disease [71,72], Brexpiprazole for the treatment of schizophrenia [73], Mardepodect for the treatment of schizophrenia [74], and Acridine carboxamide for the treatment of cancer [75].
Utilizing the Diels–Alder reaction of benzisoxazole [76,77,78] as a key step, Zhang and co-workers developed a one-pot reaction involving the denitrogenation of 2-azidobenzaldehyde 1, the formation of benzisoxazole 4, [4+2] cycloaddition with fumarate ester 2, and, finally, dehydrative aromatization of intermediate 5 for the synthesis of quinolinedicarboxylates 3 (Scheme 2) [79].
Zeng and Chen reported the Cu-catalyzed synthesis of 3-NO2 quinolines 7. The addition of nitroalkene 6 to the azide group of 1 affords 8, which then undergoes cyclization to form 9. Proton transfer and the release of N2 gas from 9 affords 10, which leads to the formation of 3-NO2 quinolines 7 after dehydration (Scheme 3) [80].
The intramolecular aza-Wittig reaction can be used for making N-heterocyclics [81,82]. Zhang and He reported the synthesis of 2,3-substituted quinolines 14 through a sequence involving the Staudinger, Knoevenagel, and aza-Wittig reactions [83,84]. The first intermediates 11 generated according to the Staudinger reaction of 2-azidobenzaldehydes 1 and PPh3 undergo the Knoevenagel reaction with different carbonyl compounds 12a–c to generate the corresponding intermediates 13a–c. The intramolecular aza-Wittig reaction releasing Ph3P=O gives 2,3-substituted quinoline products 14a–c (Scheme 4).
Zhang and co-workers expanded the scope of the aza-Wittig reaction for synthesizing 3-F quinoline 15a, 3-phosphonylquinoline 16a, and 3-sulfonylquinoline 16b using 1 and 17a or 18 as the substrates (Scheme 5) [83,85]. They also used 2-azidobenzaldehydes 1 and 1-substituted propan-2-ones 19 in the synthesis of bioactive 2-substituted quinolines such as HTLV-1 inhibitors 20a and 20b, antileishmanial agent 20c, and CF3- and CHF2-substituted quinolines 20d and 20e, shown in Scheme 6 [86,87,88].
Due to the importance of F groups in drug molecules [89,90,91,92,93], the Zhang group introduced a reaction between compounds 1 and 21 for making 2-fluorinated quinolines 22a–f, bearing CF2, CF3, and C2F5 at 70–87% yields (Scheme 7). These compounds are related to histone acetyltransferase (HAT) inhibitors [94,95,96]. Shi and co-workers reported the synthesis of 2,3-substituted quinolines 25 via a condensation/Michael/Staudinger/aza-Wittig/aromatization reaction (Scheme 8) [97]. The ortho-Azido-β-nitro-styrenes 23, synthesized by the condensation of 2-azidobenzaldehydes 1 and MeNO2, undergo the Michael addition with ketones 24 to form 26, which then reacts with PPh3 according to the Staudinger reaction to afford intermediates 27. The intramolecular aza-Wittig reaction of 27 gives 28, followed by the aromatic removal of MeNO2 to afford 25 (Scheme 8).
In addition to aza-Wittig cyclization, for making quinolines, Chassaing and co-workers reported intramolecular imine formation of aldehyde and aniline for the synthesis of 2-substituted quinolines 31. The reaction process involves the formation of ortho-azidocinnamoyl compounds 30 via the condensation of 2-azidobenzaldehydes 1 and ketones 29. The irradiation of aryl azides 30 generates nitrenes 32, which are then converted into amino intermediates 33 in protic media to give products 31 after imine cyclization (Scheme 9) [98].
Reddy and co-workers reported a cyclization reaction of azidophenyl propargyl alcohol 34 for making 2,3-substituted quinolines 35 (Scheme 10) [99]. The azidophenyl propargyl alcohol 34, generated according to the Favorskii reaction of 2-azidobenzaldehydes 1, undergoes the Ni-catalyzed addition of its R1 group to the propargylic system to form intermediates 36, followed by E/Z isomerization to afford intermediate 37. The stabilized azido group enables the subsequent denitrogenative cyclization into cyclic intermediates 38. The denickelation of 38 under the photo conditions gives intermediate 39, followed by dehydrative aromatization to afford 2,3-substituted quinolines 35.
The Yamamoto group utilized o–propargyl arylazides 40 derived from the dehydration of compound 34 for the synthesis of multi-substituted quinolines 41–44 (Scheme 11). The electrophilic cyclization of 40 in the presence of catalytic amounts of AuCl3/AgNTf2 affords products 41. The method was applied to the synthesis of 3-Br/I quinolines 42 in the presence of I2, Br2, or NIS [100]. Zhou and co-workers extended the scope of electrophilic cyclization induced by pseudohalogen (SeCN)2 for the synthesis of quinolylselenocyanates 43 [101]. Wang and Quan reported the synthesis of SCF3-substituted quinolines 44 through radical cyclization of o–propargyl arylazides 40 [102].
The ring-opening of aziridines is a useful tool for the construction of N-heterocycles via cycloaddition or cyclization reactions [103,104,105,106]. Wan and co-workers utilized ring-opening and the cyclization of aziridines 45 for the synthesis of 3-substituted quinolines 46 (Scheme 12) [107]. The TfOH-promoted denitrogenation of the azide group of 1 gave intermediate 47 and then 48 after deprotonation. The addition of 48 to aziridines 45 forms 49, followed by the cleavage of TsNH2 to afford 50. Acid-promoted cyclization of 50 gives 51, which is converted into 3-aryl quinoline 46 after aromatization (Scheme 12).

2.2. Synthesis of Polycyclic Quinolines

Polycyclic quinolines can be found in a number of commercial drugs and other bioactive compounds, such as the natural alkaloid Mappicine [108], the poly ADP ribose polymerase (PARP) inhibitor for cancer Talazoparib [109], the antibacterial drug Levofloxacin [110], the natural product Flindersine [111], and the immune response modifier Imiquimod (Figure 3) [112]. The cyclization of 2-azidobenzaldehydes can be integrated into multistep synthesis, one-pot synthesis, or a multi-component reaction (MCR) to make N-heterocycles [63,68,113,114]. The aza-Wittig cyclization-based synthesis of polycyclic quinolines is covered in this section. Shown in Scheme 13 are two pathways for the synthesis of cyclohexane-fused quinolines 55 (ee up to 98%) and 57 involving Knoevenage/aza-Wittig/dehydration reactions and Mannich/aza-Wittig/deamination sequences, respectively [115,116].
A three-component reaction (3-CR)-initiated synthesis of furan-fused quinolines was reported by Ding and co-workers (Scheme 14). Compounds 60 generated from the condensation of 2-azidobenzaldehydes 1, dialkyl acetylenedicarboxylate 58, and isocyanides 59 are used for Staudinger and aza-Wittig cyclization to make furan-fused quinolines 61 [117]. He’s group reported sequential 3-CR/Staudinger/aza-Wittig cyclization/dehydroaromatization reaction processes for making furan-fused quinolines 65 (Scheme 14) [118].
He and Bharate’s groups independently reported the reaction of aldehydes, 1,3-dicarbonyl compounds 66, amines 67, and nitroalkanes to make pyrrole-fused quinolines 69 (Scheme 15) [119,120]. He and co-workers also reported a 3-CR/Staudinger/aza-Wittig process for making pyrrole-fused quinolines 73 using 1, acetyl compounds 70, and TosMIC 71 as the starting materials (Scheme 15) [121]. Interestingly, an example of making cyclopropa[c]indeno [1,2-b]quinolines 77 was developed according to the 3-CR/Staudinger/aza-Wittig sequence. The products have a highly condensed ring system, including cyclopropane (Scheme 16) [122].
Other than aza-Wittig cyclization for the construction of quinolines, Zhang and co-workers reported cascade denitrogenation/aza-Diels–Alder/dehydrative aromatization reactions for the synthesis of pyrrolidine-2,5-dione-fused quinolines using 2-azidobenzaldehydes 1 and N-substituted maleimides 81 as the starting materials (Scheme 17) [79]. This method (Scheme 17a) is more efficient than stepwise synthesis for the synthesis of 82a (Scheme 17b) [123]. In another case, Li and Wang’s group utilized compounds 1 and 3-aza-1,6-enynes 87 as the substrates for making tetrahydrobenzo[b][1,8]naphthyridines 88 (Scheme 18) [124]. The reactions involved aza-Diels–Alder cycloaddition of intermediates 90 derived from the Au-catalyzed reaction of enynes 87 to form 91, followed by dehydrative aromatization to give products 88.
Gharpure and co-workers introduced Lewis-acid-promoted cascade reactions involving Friedel–Crafts/alkyne indol-2-yl cation cyclization/vinyl cation trapping for the synthesis of pyrrolizino-quinolines 93 [125]. Benzyl alcohol and TMSOTf promote the Friedel–Crafts reaction of 1 and indoles 92 to form 93, which undergoes alcohol elimination and cyclization to afford vinyl cations 96. The trapping of the vinyl cations with the azide group generates pyrrolizino-quinolines 93 (Scheme 19) [125]. Alves and co-workers introduced sequential [3+2] cycloaddition and condensation reactions for making triazole-fused quinolines 98 (Scheme 20) [126]. The 1,3-dipolar cycloaddition of 1 and 1,3-dicarbonyl compounds 97 leads to the formation of 1,2,3-triazoles 99. The intramolecular condensation of enolates 100 generated from the DBU deprotonation of 99 affords 101 and then triazole-fused quinolines 98 after dehydration.
Alajarin and co-workers reported the cyclization of ketenimines for making spiroquionlines 106 and 106′ using azides 102 and 102′ bearing five- and six-membered cyclic acetal functions (such as 1,3-dioxolane, 1,3-dithiolane, 1,3-dioxane, and 1,3-dithiane) as the starting materials (Scheme 21) [127,128]. The treatment of azides 102 or 102′ with PPh3 affords iminophosphorane 103 or 103′, followed by aza-Wittig reactions with disubstituted ketenes giving ketenimines 104 or 104′ and then ortho-azaxylylenes 105 or 105′ after deprotonation. The cyclization of 105 or 105′ gives the products spiroquinolines 106 or 106′.

2.3. Synthesis of 4-Hydroxyquinoline Derivatives

There are some drugs and natural products that have 4-hydroxyquinoline moiety, such as the furoquinoline alkaloid Skimmianine, with anticancer and anti-inflammatory effects [129,130]; Cabozantinib, used for the treatment of medullary thyroid cancer [131]; Tasquinimod as an immunomodulator for the treatment of blood cancers [132]; AMG-208 as a clinical trial drug for cancer [133]; Anlotinib, with antineoplastic and anti-angiogenic activities [134,135]; and Delafloxacin as a fluoroquinolone antibiotic for the treatment of acute bacterial skin and skin structure infections (Figure 4) [136].
Other than aniline-based [3+3] annulation [137] and [4+2] annulation [138] reactions for making 4-hydroxyquinolines, 2-azidobenzaldehydes have also been employed for the [4+2] annulation-based synthesis of 4-alkoxy quinolines. Gharpure and coworkers reported the reactions of 1 with hydroxyalkynes for the synthesis of different kinds of 4-alkoxy quinolines, 107, 108, and 109 (Scheme 22) [139,140,141]. The synthesis first led to the formation of oxonium ions 110 followed by intramolecular [4+2] cycloaddition and aromatization to give 4-alkoxy quinolines 109, with a new seven-membered heterocyclic ring (Scheme 22).
Metal-catalyzed 6-endo-dig azide–yne cyclization of azide-tethered alkynes 112 has been developed for the synthesis of multi-substituted 4-alkoxy quinolines 113–117 (Scheme 23) [142,143,144]. For example, Xu and coworkers synthesized 115 and 116 via the AgSbF6-catalyzed cyclization of azide-tethered alkynes. The cyclization of Ag(I)-activated alkyne-tethered azides 112 affords 118, followed by N2 gas release from α-imino silver carbenes 119 and then reaction with R1X to afford halonium zwitterions 120. After a concerted rearrangement of 120, product 115 or 116 is obtained.
Zhang and coworkers reported the direct synthesis of quinolin-4-ols, which are structurally related to histone acetyltransferase (HAT) inhibitors [145] and the key intermediates for making HMG-CoA reductase inhibitors [146]. The reaction of 1 and α-fluoro-β-ketoesters 121 or 123 via sequential aldol, aza-Wittig, and dehydrofluorinative aromatization reactions gives quinolin-4-ols 122 or 124 (Scheme 24) [83]. Green chemistry metrics analysis for this one-pot synthesis and two reported multi-step syntheses [138] of HAT inhibitor 144a was conducted [79,82,147] to validate synthetic efficiency and low waste generation (Scheme 25).

2.4. Synthesis of 4-Amino-Quinolines

Shown in Figure 5 are some 4-amino-quinoline drugs and drug candidates such as Chloroquine, Amodiaquine, Bosutinib, Amsacrine, and Dovitinib for the treatment of malarial [148,149,150], leukemia [151,152], and cancer diseases [153]. Common methods in the literature for the synthesis of 4-aminoquinolines are aniline-based multi-step reactions [96,154,155,156]. Sharada and coworkers employed azides 1 and amines 127 for the synthesis of 4-aminoquinolines 129 through the aza-Diels–Alder reaction of intermediates 128 with dimethylacetylenedicarboxylate (DMAD) (Scheme 26) [157]. Shown in Scheme 27 are two examples of quinoline synthesis using 2-azidobenzaldehyde-based [4+2] cycloadditions. In the first case of using fumarate esters as the dienophiles, quinolines 3 are generated from dehydrative aromatization involving C-O bond cleavage. In the second case of using DMAD as a dienophile for cycloaddition with 128, 4-aminoquinolines 129 result from the aromatization via the N-N bond cleavage of 130 [79,157].
Zhang and co-workers reported a three-component reaction of azides 1, α-fluoro-β-ketoesters 121, and amines 131 or 133 for the synthesis of 4-aminoquinolines 132 and 134 involving Mannich, aza-Wittig and dehydrofluorinative aromatization reactions (Scheme 28) [158]. They also applied this method to the synthesis of 2-CF3 quinolines 137a and 137b with a pyrrolidine or a piperidine at the 4-position (Scheme 29).

3. Conclusions

Presented in this paper are 2-azidobenzaldehyde-initiated reactions for the synthesis of diverse quinoline compounds, including fused, spiro-, and polycyclic quinolines, as well as substituted quinolines such as quinoline-4-ols and 4-aminoquinolines. These biologically significant quinoline compounds could be well utilized in medicinal chemistry programs for drug discovery. Also, 2-azidobenzaldehyde-initiated synthesis can be developed as one-pot stepwise synthesis or a multicomponent reaction for operation simplicity, process efficiency, and economizing in terms of steps, pots, and atoms. Some of the synthetic methods presented in this paper provide novel pathways for making quinolines which could also be used for the synthesis of other heterocyclic compounds.

Author Contributions

M.L., W.Q. and X.Z., literature search and original manuscript writing; W.Z., revision and supervision. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Conflicts of Interest

X.Z. is employee of the Cerevel Therapeutics, other authors declare no conflicts of interest.

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Molecules 29 01241 g001
Figure 1. Representative structures of quinoline drugs.
Figure 1. Representative structures of quinoline drugs.
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Scheme 1. Common synthetic strategies for making quinolines.
Scheme 1. Common synthetic strategies for making quinolines.
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Figure 2. Examples of 4-unsubstituted quinoline-based marketed drugs and clinical candidates.
Figure 2. Examples of 4-unsubstituted quinoline-based marketed drugs and clinical candidates.
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Scheme 2. Cascade reactions for quinolinedicarboxylates 3.
Scheme 2. Cascade reactions for quinolinedicarboxylates 3.
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Scheme 3. Cu-catalyzed cascade reaction for 3-NO2 quinolines 7.
Scheme 3. Cu-catalyzed cascade reaction for 3-NO2 quinolines 7.
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Scheme 4. Cascade synthesis of 2,3-substituted quinolines 14a–c.
Scheme 4. Cascade synthesis of 2,3-substituted quinolines 14a–c.
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Scheme 5. Synthesis of 3-F quinolines 15a, 3-phosphonylquinolines 16a, and 3-sulfonylquinoline 16b.
Scheme 5. Synthesis of 3-F quinolines 15a, 3-phosphonylquinolines 16a, and 3-sulfonylquinoline 16b.
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Scheme 6. Synthesis of bioactive 2-substituted quinolines 20.
Scheme 6. Synthesis of bioactive 2-substituted quinolines 20.
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Scheme 7. Direct synthesis of 2-fluorinated quinolines 22.
Scheme 7. Direct synthesis of 2-fluorinated quinolines 22.
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Scheme 8. One-pot synthesis of 2,3-substituted quinolines 25.
Scheme 8. One-pot synthesis of 2,3-substituted quinolines 25.
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Scheme 9. Photosynthesis of 2-substituted quinolines 31.
Scheme 9. Photosynthesis of 2-substituted quinolines 31.
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Scheme 10. Ni-catalyzed cyclization for making 2,3-substituted quinolines 35.
Scheme 10. Ni-catalyzed cyclization for making 2,3-substituted quinolines 35.
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Scheme 11. Alkyne–azide cyclization for making quinolines 41–44.
Scheme 11. Alkyne–azide cyclization for making quinolines 41–44.
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Scheme 12. Ring-opening and cyclization of aziridines for the synthesis of quinolines 46.
Scheme 12. Ring-opening and cyclization of aziridines for the synthesis of quinolines 46.
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Figure 3. Polycyclic quinoline-based marked drugs and natural products.
Figure 3. Polycyclic quinoline-based marked drugs and natural products.
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Scheme 13. One-pot synthesis of cyclohexane-fused quinolines 55 and 57.
Scheme 13. One-pot synthesis of cyclohexane-fused quinolines 55 and 57.
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Scheme 14. MCR-initiated synthesis of furan-fused quinolines 61 and 65.
Scheme 14. MCR-initiated synthesis of furan-fused quinolines 61 and 65.
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Scheme 15. MCR-initiated synthesis of pyrrole-fused quinolines 69 and 73.
Scheme 15. MCR-initiated synthesis of pyrrole-fused quinolines 69 and 73.
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Scheme 16. MCR-initiated synthesis of highly condensed quinolines 77.
Scheme 16. MCR-initiated synthesis of highly condensed quinolines 77.
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Scheme 17. Cascade reactions for pyrroloquinolinediones 82.
Scheme 17. Cascade reactions for pyrroloquinolinediones 82.
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Scheme 18. Cascade reactions for tetrahydrobenzo[b][1,8]naphthyridines 88.
Scheme 18. Cascade reactions for tetrahydrobenzo[b][1,8]naphthyridines 88.
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Scheme 19. Cascade synthesis of pyrrolizino-quinolines 93.
Scheme 19. Cascade synthesis of pyrrolizino-quinolines 93.
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Scheme 20. Direct synthesis of [1,2,3] triazolo[1,5-a] quinolines 98.
Scheme 20. Direct synthesis of [1,2,3] triazolo[1,5-a] quinolines 98.
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Scheme 21. Tandem synthesis of spiroquinolines 106 and 106′.
Scheme 21. Tandem synthesis of spiroquinolines 106 and 106′.
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Figure 4. Examples of 4-hydroxy and related quinolines as drug molecules.
Figure 4. Examples of 4-hydroxy and related quinolines as drug molecules.
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Scheme 22. Cascade synthesis of 4-alkoxy quinolines 107, 108, and 109.
Scheme 22. Cascade synthesis of 4-alkoxy quinolines 107, 108, and 109.
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Scheme 23. Metal-catalyzed synthesis of diverse 4-alkoxy quinolines 113–117.
Scheme 23. Metal-catalyzed synthesis of diverse 4-alkoxy quinolines 113–117.
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Scheme 24. One-pot synthesis of quinolin-4-ols 122 and 124.
Scheme 24. One-pot synthesis of quinolin-4-ols 122 and 124.
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Scheme 25. Three methods for making 122a.
Scheme 25. Three methods for making 122a.
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Figure 5. 4-Aminoquinoline-based drugs and drug candidates.
Figure 5. 4-Aminoquinoline-based drugs and drug candidates.
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Scheme 26. One-pot synthesis of 4-aminoquinolines 129.
Scheme 26. One-pot synthesis of 4-aminoquinolines 129.
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Scheme 27. Comparison of [4+2] cycloaddition for making compounds 3 and 129.
Scheme 27. Comparison of [4+2] cycloaddition for making compounds 3 and 129.
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Scheme 28. Three-component reaction to make 4-aminoquinolines 132 and 134.
Scheme 28. Three-component reaction to make 4-aminoquinolines 132 and 134.
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Scheme 29. One-pot synthesis of CF3-containing 4-aminoquinolines 137a and 137b.
Scheme 29. One-pot synthesis of CF3-containing 4-aminoquinolines 137a and 137b.
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Zhang, X.; Liu, M.; Qiu, W.; Zhang, W. 2-Azidobenzaldehyde-Based [4+2] Annulation for the Synthesis of Quinoline Derivatives. Molecules 2024, 29, 1241. https://doi.org/10.3390/molecules29061241

AMA Style

Zhang X, Liu M, Qiu W, Zhang W. 2-Azidobenzaldehyde-Based [4+2] Annulation for the Synthesis of Quinoline Derivatives. Molecules. 2024; 29(6):1241. https://doi.org/10.3390/molecules29061241

Chicago/Turabian Style

Zhang, Xiaofeng, Miao Liu, Weiqi Qiu, and Wei Zhang. 2024. "2-Azidobenzaldehyde-Based [4+2] Annulation for the Synthesis of Quinoline Derivatives" Molecules 29, no. 6: 1241. https://doi.org/10.3390/molecules29061241

APA Style

Zhang, X., Liu, M., Qiu, W., & Zhang, W. (2024). 2-Azidobenzaldehyde-Based [4+2] Annulation for the Synthesis of Quinoline Derivatives. Molecules, 29(6), 1241. https://doi.org/10.3390/molecules29061241

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