Synthesis and chemistry of 5,6-dihydropyridinium salt adducts. Synthons for general electrophilic and nucleophilic substitution of the piperidine ring system

Grierson, David S.; Harris, Martin; Husson, H.-P.

doi:10.1021/ja00523a026

Cited by 149 publications

(38 citation statements)

References 7 publications

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“…Alternatively, cation 44 may be deprotonated to the enamine 48; oxidation of the C=C double bond in 48 gives diformamide 2 [15,25,26]. Like 28 or 42, hemiaminal 47 may be also split into an equimolecular mixture of BzH and 1-benzylpiperazine (4).…”

Section: Scheme 4 Oxidation By Ruo 4 Of Piperazine Derivative 30 ([Oxmentioning

confidence: 99%

RuO4-mediated oxidation of N-benzylated tertiary amines. 3. Behavior of 1,4-dibenzylpiperazine and its oxygenated derivatives

Petride¹,

Drăghici²,

Florea³

et al. 2006

Open Chemistry

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1,4-Dibenzylpiperazine (1), -2-piperazinone (7), -2,6-piperazinedione (9), and 1-benzoyl-4-benzylpiperazine (30) were oxidized by RuO 4 (generated in situ) by attack at their endocyclic and exocyclic (i.e., benzylic) aminic N -α-C-H bonds to afford various oxygenated derivatives, including acyclic diformamides, benzaldehyde, and benzoic acid. The reaction outcome was complicated by (i) the hydrolysis of diformamides, occurred during the work-up, and (ii) the reaction of benzaldehyde with the hydrolysis-derived amines giving imidazolidines and/or Schiff bases. Benzoic acid resulted from benzaldehyde only. Compounds 7, 30, and 1-benzylpiperazine, but not 9, were transiently formed during the oxidation of 1. In the same reaction conditions, 1,4-dibenzyl-2,3-(or 2,5)-piperazinedione, 1,4-dibenzyl-2,3,6-piperazinetrione, 4-benzoyl-1-benzyl-2-piperazinone, and 1,4-dibenzoylpiperazine were inert. The proposed oxidation mechanism involves the formation of endocyclic and exocyclic iminium cations, as well as of cyclic enamines. The latter intermediates probably result by base-induced deprotonation of the iminium cations, provided an N + −β-proton is available. In the case of 1, the cations were trapped with NaCN as the corresponding α-aminonitriles. The statistically corrected regioselectivity (endocyclic/exocyclic) of the RuO 4 -induced oxidation reaction of 1, 7, and 30 was 1.2-1.3.

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Section: Scheme 4 Oxidation By Ruo 4 Of Piperazine Derivative 30 ([Oxmentioning

confidence: 99%

RuO4-mediated oxidation of N-benzylated tertiary amines. 3. Behavior of 1,4-dibenzylpiperazine and its oxygenated derivatives

Petride¹,

Drăghici²,

Florea³

et al. 2006

Open Chemistry

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“…To circumvent these problems, we developed a practical synthesis of the key intermediate (6)-2 0 -cyanonicotine 3 using the Polonovski reaction [25,26]. The Noxides 2 of nicotine were reacted with trifluoroacetic anhydride; the iminium intermediate then reacted with the cyano ion (Scheme 3).…”

Section: Resultsmentioning

confidence: 99%

Racemic synthesis of 2′‐substituted nicotine analogs

Rouchaud

Kem

2011

Journal of Heterocyclic Chem

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The chemical and pharmacological properties of 2′‐substituted nicotines are poorly understood relative to other substituted nicotines. We developed a practical synthesis of the key intermediate (±)‐2′‐cyanonicotine using the Polonovski reaction. Alkylation of (±)‐2′‐cyanonicotine with Grignard reagents led to several 2′‐alkylnicotines; (±)‐2′‐aminomethylnicotine, (±)‐2′‐hydroxymethylnicotine, and (±)‐2′‐carbamoylnicotine were also synthesized. J. Heterocyclic Chem., (2012).

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“…[15] These tetrahydropyridines were obtained with yields of between 61 and 63 % and were subsequently oxidized with metachloroperbenzoic acid (1.2 to 1.5 equivalents) at 0°C to avoid the possible epoxidation of the double bond. The Noxide derivatives 16a,b were characterized and then converted into their respective dihydropyridinium salts 18a,b in a Polonovsky-Potier reaction [16] with trifluoroacetic anhydride (1.5 to 2 equivalents) to afford the intermediate salts 17a and 17b. These salts are very unstable and cannot be purified.…”

Section: Preparation Of 1456-tetrahydropyridinesmentioning

confidence: 99%

Synthesis of New Azocine Derivatives and Their Functionalization by Nucleophilic Addition to Their Iminium Salts

Trindade¹,

Santos²,

Gil³

et al. 2005

Eur J Org Chem

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A route to the eight‐membered nitrogen heterocycles 20a,b is described starting from the 3‐alkyl‐N‐benzylpyridinium salts 14a,b. These azocine derivatives were converted into their respective iminium salts 11 by treatment with methanesulfonic acid. A study concerning the regioselectivity of nucleophilic additions to these salts is presented. Nucleophiles like hydride or Grignard reagents react selectively in the 2‐position to give adducts such as 22 and 23, while azide and phenylthiolate attack the 6‐position to give 24 and 25, respectively. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

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Synthesis and chemistry of 5,6-dihydropyridinium salt adducts. Synthons for general electrophilic and nucleophilic substitution of the piperidine ring system

Cited by 149 publications

References 7 publications

RuO4-mediated oxidation of N-benzylated tertiary amines. 3. Behavior of 1,4-dibenzylpiperazine and its oxygenated derivatives

RuO4-mediated oxidation of N-benzylated tertiary amines. 3. Behavior of 1,4-dibenzylpiperazine and its oxygenated derivatives

Racemic synthesis of 2′‐substituted nicotine analogs

Synthesis of New Azocine Derivatives and Their Functionalization by Nucleophilic Addition to Their Iminium Salts

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