Meta bridging reactions of electron-deficient aromatics. I. One-step synthesis of the 6,7-benzomorphan ring system. Facile preparation of potential narcotic antagonists

Bard, Raymond R.; Strauss, Michael J.

doi:10.1021/ja00846a039

Cited by 22 publications

(4 citation statements)

References 5 publications

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“…24 However, in contrast to the present observation of carbon protonation, it was found in a previous study 25 that the phenoxide C-adduct of 1,3,5-trinitrobenzene 6 is protonated in aqueous H 2 SO 4 or HCl on oxygen to give the nitronic acid derivative 9 for which a pK a of -1.2 was found. This contrasting behavior can be understood on the basis that in 6 the nitro group is part of a conjugated system, whereas in 1 the C(2)-NO 2 is isolated as discussed above.…”

Section: Reaction Pathways In σ-Complex Formationcontrasting

confidence: 99%

“…With regard to the above discussion, it is interesting to note that reaction of TNB with enamines affords N,C-cyclo diadducts that are also characterized by a ring protonation at C-2 . However, in contrast to the present observation of carbon protonation, it was found in a previous study that the phenoxide C-adduct of 1,3,5-trinitrobenzene 6 is protonated in aqueous H 2 SO 4 or HCl on oxygen to give the nitronic acid derivative 9 for which a p K a of −1.2 was found.…”

Section: Discussioncontrasting

confidence: 53%

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An Unexpected Ring Protonation in Meisenheimer Complex Formation

Manderville

Buncel

1997

J. Org. Chem.

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The reactions of N,N-dimethylpicramide (DMP) with phenoxide and 2,6-di-tert-butylphenoxide ions have been monitored by 1 H and 13 C NMR spectroscopy in dimethyl sulfoxide at room temperature. Both aryloxide nucleophiles react at the unsubstituted (C-3) position of DMP to produce para carbonbonded σ-adducts (Meisenheimer complexes, 1 and 3, respectively). Surprisingly, acidification of these Meisenheimer complexes led to a ring protonation resulting in production of nitro tautomers (2 and 4) with a sp 3 -bound NO 2 group at the C-2 position. For 4, the C-2 nitro tautomer of the 2,6-di-tert-butylphenoxide adduct of DMP (3), a pK a value of 6.2 was determined in aqueous solution. Insight into electronic factors that could provide a driving force for ring protonation was derived from examination of the 13 C NMR parameters of the Meisenheimer complexes and the C-2 nitro tautomers. These parameters were consistent with the notion that the C-2 protonation stemmed from charge transfer interactions from the C-1 NMe 2 substituent to the C-2 NO 2 group ("enamine") and the attendant relief in steric strain upon conversion of the C-2 center from sp 2 to sp 3 .

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Section: Reaction Pathways In σ-Complex Formationcontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 53%

An Unexpected Ring Protonation in Meisenheimer Complex Formation

Manderville

Buncel

1997

J. Org. Chem.

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“…We recently reported the novel meta-bridging reactions1 of electron-deficient benzenes and naphthalenes with amidines. 2 The initial products of such reactions are com-plexes3-5 which in certain instances undergo intramolecular cyclization to give meta-bridged products. 6 The reaction is a useful synthesis of l,5-methano-3-benzazocines (6,7-benzomorphans), potentially useful narcotic antagonists.7'8 Several of the 3-benzazocine amidinium nitronates which we have prepared (vide infra) are long-acting narcotic antagonists in mice.9 We present here a detailed product study involving reactions of deuterium labeled napthalenes which provides evidence for isomeric modes of bridging.…”

mentioning

confidence: 99%

Meta bridging reactions of electron-deficient aromatics. 3. Isomeric bridging of di-, tri-, and tetranitronaphthalenes to 2- and 3-benzazocines

Bard¹,

Strauss²

1976

J. Org. Chem.

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“…This was filtered off and recrystallized from CH3CN to yield 0.9 g of 15b, mp 291-293 °C. The -NMR spectrum (Me2SO-dg) shows absorptions at 3.80 (2 H. m, CH2CH2), 4.28 (2 H, m, CH2CH2), 7.65 (5 H, m, Ar), 8.00 (1 H, br s, OH), 9.16 (1 H, d, J = 2 Hz, nitroaromatic ring proton), and 9.28 (1 H, d, J = 2 Hz, nitroaromatic ring proton). The mass spectrum shows a parent peak at m/e 352.…”

Section: Methodsmentioning

confidence: 99%