An improvement in the Doebner-Miller synthesis of quinaldines

Leir, Charles M.

doi:10.1021/jo00425a036

Cited by 61 publications

(17 citation statements)

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“…The zwitterionic unsymmetrical squaraine dye 10 was prepared by a base-catalyzed condensation of intermediate 6 with the iodoquinoline-based quaternary ammonium salt 9, in a n-butanol/pyridine refluxing mixture. Ammonium salt 9 was prepared by the alkylation of 6-iodo-1-hexylquinaldine (8) with iodohexane [49], obtained by the described Doebner-Miller reaction between 4-iodoaniline (7) and crotonaldehyde in hydrochloric acid [48,59]. Methylation of the unsubstituted squaraine dye 10 with methyl trifluoromethanesulfonate produced the O-methyl ether intermediate 11 [4].…”

Section: Synthesis and Characterizationmentioning

confidence: 99%

Photophysicochemical Properties and In Vitro Phototherapeutic Effects of Iodoquinoline- and Benzothiazole-Derived Unsymmetrical Squaraine Cyanine Dyes

et al. 2019

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The search to replace conventional cancer treatment therapies, such as chemotherapy, radiotherapy and surgery has led over the last ten years, to a substantial effort in the development of several classes of photodynamic therapy photosensitizers with desired photophysicochemical and photobiological properties.Herein we report the synthesis of 6-iodoquinoline-and benzothiazole-based unsymmetrical squaraine cyanine dyes functionalized with amine groups located in the four-membered central ring. Their photodegradation and singlet oxygen production ability, as well as their in vitro photocytotoxicity against Caco-2 and HepG2 cell lines using a 630.8 ± 0.8 nm centered light-emitting diode system, were also investigated. All photosensitizer candidates displayed strong absorption within the tissue transparency spectral region (650-850 nm). The synthesized dyes were found to have moderate light stability. The potential of these compounds is evidenced by their cytotoxic activity against both tumor cell lines, highlighting the zwitterionic unsubstituted dye, which showed more intense photodynamic activity. Although the singlet oxygen quantum yields of these iodinated derivatives are considered low, it could be concluded that their introduction into the quinoline heterocycle was highly advantageous as it played a role in increasing selective cytotoxicity in the presence of light. Thus, the novel synthesized dyes present photophysicochemical and in vitro photobiological properties that make them excellent photosensitizer candidates for photodynamic therapy.

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Section: Synthesis and Characterizationmentioning

confidence: 99%

Photophysicochemical Properties and In Vitro Phototherapeutic Effects of Iodoquinoline- and Benzothiazole-Derived Unsymmetrical Squaraine Cyanine Dyes

et al. 2019

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“…Firstly, methoxyquinoline 4 was synthesized starting from o-anisidine (2) and methacrolein (3) by a Skraup-Döbner-von Miller quinoline synthesis. [23] Deprotection of the methyl ether was achieved by treatment with boron tribromide in dichloromethane to form hydroxyquinoline 5. After introduction of the Boc group, the methyl group in quinoline 6 was brominated by using N-bromosuccinimide (NBS) in CCl 4 , which provided desired receptor arm 7 in moderate yields.…”

Section: Synthesis Of Ligandmentioning

confidence: 99%

Controlling the Helicity of Hydroxyquinoline Metal Complexes Based on a Macrocyclic Peptide Scaffold

Ziegler

Haberhauer

2009

Eur J Org Chem

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“…Aromatic amines with ortho substituents give the 8-substituted isomers [15], while 3-(meta)-substituted anilines give 7-and 5-substituted derivatives of quinoline. As a rule the 7-substituted isomers predominate, while in some cases the 5-substituted quinoline is not observed at all [41]. The same tendency is observed if other carbonyl compounds, such as the products from crotonic condensation of cyclohexanone, methyl isobutyl ketone, and methyl ethyl ketone, are used instead of crotonaldehyde [15,16].…”

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confidence: 89%

Traditional and modern approaches to the synthesis of quinoline systems by the Skraup and Doebner-Miller methods. (Review)

Yamashkin

Oreshkina

2006

Chem Heterocycl Compd

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Recent data on classical and modified methods for the synthesis of quinoline systems by the Skraup andDoebner-Miller reactions, not included in reviews on heterocycles, are discussed.The need for compounds containing a quinoline fragment in various regions of human activity has increased in recent times. The great attention paid by researchers to the study of quinoline derivatives is explained by the fact that these compounds exhibit a broad range of antimicrobial activity [1-4] and, particularly, antitubercular activity [5] and antimalarial activity [6,7] and are also present in antiallergic and antiasthmatic agents [8]. Classical methods are widely used for their synthesis, and two of these are discussed in the present review.The most important way of constructing the quinoline system involves the cyclization of a substituent in the side chain of a benzene ring. This applies to the synthesis of quinolines by the Skraup and Doebner-Miller reactions. In the classical form, however, these syntheses take place under fairly harsh conditions, and this reduces their preparative value. In recent years, however, the efforts of synthetic chemists have been directed toward modification of these methods. Both traditional and modified approaches to the synthesis are discussed in this review.The first report on the synthesis of quinoline, realized by passing the vapor of ethylaniline and other alkylanilines over heated lead oxide, was published by Koenigs in 1879; in another method (1880) quinoline was obtained by heating the product from the addition of acrolein to aniline. Soon after this Skraup (1880) [9] and Doebner and Miller (1881) put forward their methods [10]; both these syntheses are close to Koenigs' acrolein method and have found widespread application. THE SKRAUP AND DOEBNER-MILLER REACTIONS (THE TRADITIONAL APPROACH)The construction of the quinoline system by the Skraup and Doebner-Miller methods is based on the reaction of an aromatic amine containing at least one free ortho position with a reagent providing a source of the three-carbon fragment.In the classical Skraup method the aromatic amine is heated with glycerol (1), sulfuric acid (which catalyzes the dehydration of glycerol to acrolein (2)), and an oxidizing agent 7, transforming the initially formed 1,2-dihydroquinoline (6) into the fully aromatized heterocycle 8. In the simplest case, with aniline (3) as amine and nitrobenzene (7) as oxidizing agent, the reaction is represented by the following scheme [11]. __________________________________________________________________________________________

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An improvement in the Doebner-Miller synthesis of quinaldines

Cited by 61 publications

References 1 publication

Photophysicochemical Properties and In Vitro Phototherapeutic Effects of Iodoquinoline- and Benzothiazole-Derived Unsymmetrical Squaraine Cyanine Dyes

Photophysicochemical Properties and In Vitro Phototherapeutic Effects of Iodoquinoline- and Benzothiazole-Derived Unsymmetrical Squaraine Cyanine Dyes

Controlling the Helicity of Hydroxyquinoline Metal Complexes Based on a Macrocyclic Peptide Scaffold

Traditional and modern approaches to the synthesis of quinoline systems by the Skraup and Doebner-Miller methods. (Review)

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