Regiochemistry of nucleophilic substitution of 4-phenylsulfonyl tetrafluoropyridine with unequal bidentate nucleophiles

Ranjbar‐Karimi, Reza; Mousavi, Mirrasoul

doi:10.1016/j.jfluchem.2010.01.006

Cited by 28 publications

(15 citation statements)

References 17 publications

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“…[7] Hence 4-aminopyridine derivatives with additional fluorine substituents on the ring are easily accessible [10] and serve as potential precursors for compounds such as 2 and 3. The catalytic hydrodefluorination (HDF), that is, the conversion of CÀF into CÀH bonds, has been extensively studied; [8] however, due to the high cost of most reagents and catalysts as well as limitations in the substrate scope it is scarcely used for synthetic applications.…”

Section: Dedicated To the Bayer Company On The Occasion Of Its 150th mentioning

confidence: 99%

Selective Catalytic Hydrodefluorination as a Key Step for the Synthesis of Hitherto Inaccessible Aminopyridine Derivatives

2013

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Dedicated to the Bayer company on the occasion of its 150th anniversaryThe synthesis of specifically substituted pyridines is a permanent challenge since new derivatives of this class of heterocycles are required as building blocks for supramolecular chemistry, as components of new materials, and also in pharmaceutical science.[1]4-(Dimethylamino)pyridine (DMAP) (1) is a frequently used basic catalyst in many important synthetic transformations, [2] but it also strongly stabilizes nanoparticles by coordination of the Lewis basic nitrogen to the metal surface.[3] Due to our interest in multivalent ligands [4] we set out to synthesize divalent analogues of 1, in particular, compounds 2 and 3 (Scheme 1).[5] Whereas compound 2 was available in moderate yield by the nucleophilic substitution of 4-chloropyridine employing the appropriate diamine, the chiral divalent compound 3 with a more rigid backbone could not be prepared. Neither were the nucleophilic substitutions of 4-halopyridines with trans-1,2-diaminocyclohexane in the presence or absence of palladium catalysts successful, [6] nor were reactions with 4-(methylamino)pyridine as the nucleophile in its reactions with difunctionalized cyclohexane derivatives. [5] The high steric hindrance seems to hamper these substitution reactions.Thus we developed a new synthetic strategy for the preparation of 3 based on two key reactions: nucleophilic substitution of the (oligo)fluorinated pyridines [7] and subsequent conversion of CÀF into CÀH bonds by catalytic hydrodefluorination (HDF). [8,9] The strong electron-withdrawing effect of the fluorine substituents in fluorinated pyridine derivatives allows the selective substitution of fluoride by nucleophiles at the 4-or 2-/6-positions of the heterocyclic ring.[7] Hence 4-aminopyridine derivatives with additional fluorine substituents on the ring are easily accessible [10] and serve as potential precursors for compounds such as 2 and 3. The catalytic hydrodefluorination (HDF), that is, the conversion of CÀF into CÀH bonds, has been extensively studied; [8] however, due to the high cost of most reagents and catalysts as well as limitations in the substrate scope it is scarcely used for synthetic applications.[9] Our synthetic strategy to prepare hitherto inaccessible aminopyridine derivatives used the detour employing the nucleophilic aromatic substitution to create the CÀN bond followed by catalytic HDF. For this purpose we used the [Cp 2 TiF 2 ]/ diphenylsilane system, recently developed for the defluorination of fluoroalkenes. [11,12] To prove the viability of the catalytic HDF of fluorinated aminopyridines, we used 2,3,5,6-tetrafluoro-4-morpholinopyridine (4) as a model substrate in 1,4-dioxane as the solvent (Scheme 2). Under optimized conditions at temperatures between 90 to 110 8C with 15 mol % of the precatalyst we obtained the twofold hydrodefluorinated product 6 in 95 % yield. These conditions allow the regioselective substitution of the more reactive fluorine atoms at C-2 and C-6.[7] Lower loadings of the precatalyst...

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Section: Dedicated To the Bayer Company On The Occasion Of Its 150th mentioning

confidence: 99%

Selective Catalytic Hydrodefluorination as a Key Step for the Synthesis of Hitherto Inaccessible Aminopyridine Derivatives

2013

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“…In recent years, we and others have described synthesis of some bipyridyl bridged compounds (Ranjbar-Karimi et al, 2011a, b), macrocycles (Sandford, 2003) and ring-fused systems (Barone et al, 2005;Sandford et al, 2005;Hargreaves et al, 2007;Ranjbar-Karimi et al, 2011a, b;Sandford, 2003;Ranjbar-Karimi et al, 2012;Ranjbar-Karimi and Mousavi, 2010) from reaction of pentafluoropyridine and derivatives with some appropriate nucleophiles and binucleophiles (N, O, S nucleophiles) for example Sandford et al reported synthesis of some dipyridoimidazole and imidazopyridine derivatives from highly fluorinated pyridine systems, 2-aminopyridine derivatives, and amidines respectively (Cartwright et al, 2007(Cartwright et al, , 2010. Previously we reported the use of ultrasound irradiation for reaction of pentafluoropyridine with mono-and bidentate Nnucleophiles (Ranjbar-Karimi et al, 2011a).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of some fluorinated thiazolopyridine from pentafluoropyridine and 4-phenylsulfonyl tetrafluoropyridine

Ranjbar‐Karimi

Danesteh

Beiki-Shoraki

2019

Arabian Journal of Chemistry

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In this study, the reaction of pentafluoropyridine and 4-phenylsulfonyl tetrafluoropyridine with difunctional nitrogen and sulfur nucleophiles such as thiourea, thioamide derivatives, and unsymmetrical bidentate nitrogen nucleophiles such as diamino-triazole and amino-imidazole in the presence of sodium carbonate was investigated. ª 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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“…Substitution patterns available by stepwise replacement of fluorines are different from those afforded by electrophilic aromatic substitution and allow preparation of diverse structural types [7,8]. Potential for ring formation with bidentate nucleophiles [9,10], control of regiochemistry through hard/soft nucleophilic interactions [11, 12,], and alternative methods for promoting reaction by ultrasound [13] continue to attract attention. Retaining fluorine in a molecule is also desirable from a medicinal chemistry perspective, since fluorine can improve resistance to metabolism due to the strong C-F bond (485 kJmol -1 ) while the small size (van der Waals radius, 1.47 Å) and high electronegativity (3.98 Pauling scale) endow specific electronic properties that can dramatically alter the biological response of the compound [14,15].…”

Section: Introductionmentioning

confidence: 99%

Novel fluorinated benzimidazole-based scaffolds and their anticancer activity in vitro

Bhambra

Edgar

Elsegood

et al. 2016

Journal of Fluorine Chemistry

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Regiochemistry of nucleophilic substitution of 4-phenylsulfonyl tetrafluoropyridine with unequal bidentate nucleophiles

Cited by 28 publications

References 17 publications

Selective Catalytic Hydrodefluorination as a Key Step for the Synthesis of Hitherto Inaccessible Aminopyridine Derivatives

Selective Catalytic Hydrodefluorination as a Key Step for the Synthesis of Hitherto Inaccessible Aminopyridine Derivatives

Synthesis of some fluorinated thiazolopyridine from pentafluoropyridine and 4-phenylsulfonyl tetrafluoropyridine

Novel fluorinated benzimidazole-based scaffolds and their anticancer activity in vitro

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