Trifluoroacetylation of Methylpyridines and Other Methylazines: A Convenient Access to Trifluoroacetonylazines

Kawase, Masami; Teshima, Mutsumi; Saito, Setsuo; Tani, Shigemasa

doi:10.3987/com-98-8268

Cited by 39 publications

(36 citation statements)

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“…1,2-dihydropyrrolo[1,2-a]pyrazine (11), 1-(3,3,3-fluoro-2-oxopropylidene)-6-(trifluoroacetyl)-1,2-dihydropyrrolo-[1,2-a]pyrazine (12), and 1-(3,3,3-trifluoro-2-oxopropylidene)-8-(trifluoroacetyl)-1,2-dihydropyrrolo[1,2-a]-pyrazine (13 Similar trifluoroacetylation results leading to trifluoroacetonyl derivatives were obtained previously for methyl-substituted azines such as pyridine or pyrimidine [8]. Pyridine was shown to promote this reaction.…”

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confidence: 58%

Trifluoroacetylation of pyrrolo[1,2-a]pyrazines

Теренин

Kabanova

Tselishcheva

et al. 2007

Chem Heterocycl Comp

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A study was carried out on the reaction of pyrrolo [1,2-a]pyrazines containing an alkyl, aryl, or aralkyl substituent at C-1 with trifluoroacetic anhydride. Trifluoroacetylation products may be formed either by reaction in the pyrrole ring or at the aryl or aralkyl groups at C-1. Products of electrophilic substitution at C-6 are formed in the trifluoroacetylation of pyrrolo [1,2-a]pyrazines containing at C-1 a substituent bulkier than a methyl group but lacking substituents at C-6 (the α-position of the pyrrole ring).The pyrrolo[1,2-a]pyrazine bicyclic aromatic system has not been studied extensively, perhaps due to the difficulties in its preparation and its relatively low reactivity. The relative stability of the pyrrolo[1,2-a]pyrazine system to the action of weak electrophilic agents is indicated, for example, by the formation of the 6-acetyl derivative in only 16% yield upon heating 1,7-dimethylpyrrolo[1,2-a]pyrazine with excess acetic anhydride at reflux for 24 h [1]. The bromination of unsubstituted pyrrolo[1,2-a]pyrazine leads to a 1:1 mixture of 8-bromo and 6,8-dibromo derivatives [2, 3], while formylation of this model leads to 8-formylpyrrolo[1,2-a]pyrazine in 60% yield as the authors [2] affirm, although the 1 H NMR spectrum given for this compound leaves doubt concerning its structural identification. Paudler and Dunham [3] were unable to formylate unsubstituted pyrrolo[1,2-a]pyrazine by the Vilsmeier-Haack procedure. Attempts to obtain nitroso or azo derivatives of pyrrolo[1,2-a]pyrazines in reactions with nitrous acid and phenyldiazonium chloride also proved unsuccessful [4].Hence, we undertook a systematic study of the behavior of pyrrolo[1,2-a]pyrazines 1-10 in reactions with electrophiles such as acylation with trifluoroacetic anhydride, which is a stronger acylating agent than acetic anhydride. The trifluoroacetyl cation is a rather strong electrophile. Thus, the acylation of pyrroles by trifluoroacetic anhydride proceeds rapidly at 0°C [5]. In previous work [6], we showed that dipyrrolo[1,2-a:2',1'-c]pyrazines form ditrifluoroacetyl derivatives as the major reaction products with excess trifluoroacetic anhydride even at room temperature. On the other hand, much more complicated behavior is found for 3,4-dihydropyrrolo[1,2-a]pyrazines, for which the direction of the reaction depends on the structure of the starting compounds and substrate/reagent ratio [7].The α-position of the pyrrole ring in 1-methylpyrrolo[1,2-a]pyrazine (1) is unoccupied and we might expect that the most likely product in its reaction with trifluoroacetic anhydride would be 6-trifluoroacetylpyrrolo[1,2-a]pyrazine by analogy to acylation by acetic anhydride [1]. However, the reaction of 1 with a 2.5-fold excess of trifluoroacetic anhydride in benzene (method A) yielded three products. NMR spectroscopy and mass spectrometry indicated the formation of 1-(3,3,3-trifluoro-2-oxopropylidene)-__________________________________________________________________________________________ M. V. Lomonosov

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confidence: 58%

Trifluoroacetylation of pyrrolo[1,2-a]pyrazines

Теренин

Kabanova

Tselishcheva

et al. 2007

Chem Heterocycl Comp

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“…Our synthetic protocol to obtain the ligand 1a consists of a trifluoroacetylation of 2-methylbenzoxazole with trifluoroacetic anhydride (TFAA) in the presence of pyridine 24) (Chart 1). The Zn(II) complex 2a was prepared by the reaction of 1a with zinc dust in MeCN in 78% yield, consisting of 1a with zinc(II) ion in 2 : 1 ratio.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Antimicrobial Activity of 2-Trifluoroacetonylbenzoxazole Ligands and Their Metal Complexes

et al. 2018

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Key words antibacterial activity; fluorinated benzoxazole; metal complex; trifluoroacetylBacterial infection remains a serious threat to human lives due to rapid development of resistance to the existing antibiotics. In order to prevent this major medical problem, the discovery of new types of antimicrobial agents is a very important but challenging task.1,2) Transition metal complexes have received great attention because many drugs such as antibiotics and quinolone antibiotics possess better pharmaceutical properties when they are in the form of metal complexes. 3-7)Benzoxazole heterocycle system is an important pharmacophore and privileged structure in the medicinal chemistry. 8-10)Its derivatives and particularly, 2-substituted benzoxazoles exert various biological activities such as antimicrobial, antiviral, antifungal, and anticancer. [11][12][13][14][15] In previous studies, we have identified 2-trifluoroacetonylbenzoxazole (1a) with in vitro antimicrobial activity against Helicobacter pylori and Escherichia coli (Ec) from our compound library of trifluoromethyl ketones obtained by our developed reactions. 16,17) The heteroaryl-substituted alkenol systems such as 1a are known to chelate some metal ions such as aluminum 18) and to form a stable six-membered metal complexes in a bidentate mode, where the complexes were reinforced by a positive inductive effect of the heterocyclic moiety and a negative inductive effect of the CF 3 groups. [19][20][21][22][23] In the light of these knowledge, three 2-fluoroacetonylbenzoxazole ligands 1a-c and their new Zn(II) complexes 2a-c have been synthesized in order to check how the metal ion binding may influence their antibacterial activity (Chart 1). In addition, syntheses of new metal [Mg(II), Ni(II), Cu(II), Pd(II), and Ag(I)] complexes 2d-h from 1a have been also described ( Table 1). The structures of six metal complexes 2b and 2d-h were determined by single-crystal X-ray diffraction analyses. In vitro antimicrobial activities of the ligands 1a-c and their metal complexes 2a-h were investigated against six Gram-positive (G(+)) and six Gram-negative (G(−)) bacteria and the results were compared with those of silver nitrate and appropriate antibiotics such as Kanamycin, Gentamicin, Norfloxacin, and/or Linezolid. The most potent Ag(I) complex 2h is bacteriostatic, disrupts membrane integrity observed by scanning electron microscopy (SEM) and is less likely to develop resistance development against Pseudomonas aeruginosa (Pa). Results and DiscussionChemistry First, three benzoxazole ligands 1a-c and their new Zn(II) complexes 2a-c have been prepared in order to investigate the relationship of the ligands and their Zn(II) complexes with their antibacterial activities.Our synthetic protocol to obtain the ligand 1a consists of a trifluoroacetylation of 2-methylbenzoxazole with trifluoroacetic anhydride (TFAA) in the presence of pyridine 24) (Chart 1). The Zn(II) complex 2a was prepared by the reaction of 1a with zinc dust in MeCN in 78% yield, consisting of 1a with zinc(...

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“…Compounds 1a-1c (Scheme 1 and Table 1) were prepared as previously published: 1a [5], 1b, 1c [12] and compound 2 was prepared from the bromination of compound 1a [5]. Substitutions (R 1 , R 2 , R 3 ) on 2-ketomeethylquinolines are presented in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…for C12 H 9 F 2 NO: NMR (75 MHz, CDCl 3 ): δ (ppm) 180.78 (C=O), 155.00 (C), 138.36 (CH), 136.00 (C), 132.12 (CH), 128.28 (CH), 125.24 (CH), 122.04 (C), 118.50 (CH), 111.46 (CH). 92.00 (CHF 2 ), 87.39 (=CH); 19 F NMR (500 MHz, CDCl 3 ): δ ( ppm) 76.51, 55.61.1,1,1-Trifluoro-3-(1H-quinolin-2-ylidene)propan-2-one (1b).This compound was prepared by following the method previously published by Kawase et al[12]. Yield: 0.5 g, 70%, m.p.…”

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confidence: 99%

“…Crystal data: C12 H 9 F 2 NO, M = 221.2, monoclinic, space group P2 1 /c, a = 4.3753 (9), b = 19.402 (3), c = 11.5506 (19) Å, β = 95.02 (2)°, V = 976.8 (3) Å 3 , Z = 4, D c = 1.504 g cm -3 , μ = 0.12 mm -1 (MoKα, λ = 0.71073 Å), T = 150 K. Of 16866 reflections measured on a Bruker-Nonius KappaCCD diffractometer, 1710 were unique (θ < 25°, R int = 0.0337). The structure was solved by direct methods and refined on F 2 values.…”

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confidence: 99%

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Preparation, reactivity and tautomeric preferences of novel (1H-quinolin-2-ylidene)propan-2-ones

Loghmani-Khouzani

Osmailowski²,

Gawinecki³

et al. 2006

JICS

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1,1-Difluoro-3-(1H-quinolin-2-ylidene)propan-2-one 1a, 1,1,1-trifluoro-3-(1H-quinolin-2-ylidene)propan-2-one 1b, 1,1,1-trifluoro-3-(4-chloro-1H-quinolin-2-ylidene)propan-2-one 1c and 1,3-dibromo-1,1-difluoro-3-(2-quinolyl)propan-2-one 2 are prepared and characterized by various spectroscopic techniques. The crystal structure of 1a is determined by X-ray diffraction. Furthermore, a series of previously known non-halogenated (1H-quinolin-2-ylidene)propan-2-ones 1d-1h are oxidized with AgBrO 3 in the presence of AlCl 3 . In all cases, 2-(1-bromo-1-chloromethyl)quinoline 3 is obtained in high yield. The bromination order and sites of 1a are analyzed based on ab initio MP2 and DFT calculations for the molecule and its anions.

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Trifluoroacetylation of Methylpyridines and Other Methylazines: A Convenient Access to Trifluoroacetonylazines

Cited by 39 publications

References 0 publications

Trifluoroacetylation of pyrrolo[1,2-a]pyrazines

Trifluoroacetylation of pyrrolo[1,2-a]pyrazines

Synthesis and Antimicrobial Activity of 2-Trifluoroacetonylbenzoxazole Ligands and Their Metal Complexes

Preparation, reactivity and tautomeric preferences of novel (1H-quinolin-2-ylidene)propan-2-ones

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