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Volumn 73, Issue 24, 2008, Pages 9610-9618

Synthesis of a 7-azaindole by chichibabin cyclization: Reversible base-mediated dimerization of 3-picolines

Author keywords

[No Author keywords available]

Indexed keywords

AZAINDOLE; BENZONITRILE; CHEMICAL EQUATIONS; IR AND NMR SPECTROSCOPIES; KEY INTERMEDIATES; LITHIUM DIISOPROPYLAMIDE; REACTION COORDINATES; REACTION MECHANISMS; SOLUTION STRUCTURES; STARTING MATERIALS;

EID: 58049217579     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo801410s     Document Type: Article
Times cited : (34)

References (138)
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    • 19F NMR spectroscopy, see: (a) Gakh, Y. G.; Gakh, A. A.; Gronenborn, A. M. Magn. Reson. Chem. 2000, 38, 551.
    • 19F NMR spectroscopy, see: (a) Gakh, Y. G.; Gakh, A. A.; Gronenborn, A. M. Magn. Reson. Chem. 2000, 38, 551.
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    • Scheme 2 does not represent a comprehensive profile of byproducts
    • Scheme 2 does not represent a comprehensive profile of byproducts.
  • 24
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    • 2 rearomatization, see: (a) Godard, A.; Jacquelin, J. M.; Quéguiner, G. J. Organomet. Chem. 1988, 354, 273.
    • 2 rearomatization, see: (a) Godard, A.; Jacquelin, J. M.; Quéguiner, G. J. Organomet. Chem. 1988, 354, 273.
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    • For the 1,2-addition of an aryllithium to 1, see: DuPriest, M. T.; Schmidt, C. L.; Kuzmich, D.; Williams, S. B. J. Org. Chem. 1986, 51, 2021.
    • For the 1,2-addition of an aryllithium to 1, see: DuPriest, M. T.; Schmidt, C. L.; Kuzmich, D.; Williams, S. B. J. Org. Chem. 1986, 51, 2021.
  • 27
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    • Dimer 9 was further characterized by X-ray crystallography. The product of oxidative coupling (i) was also characterized as a rogue crystal by X-ray crystallography. We were unable to intentionally produce detectable i by introducing oxygen to an LDA/1 mixture. (Chemical Equation Presented)
    • Dimer 9 was further characterized by X-ray crystallography. The product of oxidative coupling (i) was also characterized as a rogue crystal by X-ray crystallography. We were unable to intentionally produce detectable i by introducing oxygen to an LDA/1 mixture. (Chemical Equation Presented)
  • 28
    • 58049199618 scopus 로고    scopus 로고
    • We find fluoropyridines to be sensitive to traces of acid, including the residual HCl in chlorinated solvents
    • We find fluoropyridines to be sensitive to traces of acid, including the residual HCl in chlorinated solvents.
  • 33
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    • Traces (approx 5, of 13(δ-77.9 ppm) are also observed
    • Traces (approx 5%) of 13(δ-77.9 ppm) are also observed.
  • 34
    • 58049212379 scopus 로고    scopus 로고
    • Lithiation of an isolated sample of 9 with LDA affords new 19 F resonances at δ-78.9 and-75.0 ppm that we attribute to ii. These resonances were not observed in the reaction mixture.
    • Lithiation of an isolated sample of 9 with LDA affords new 19 F resonances at δ-78.9 and-75.0 ppm that we attribute to ii. These resonances were not observed in the reaction mixture.
  • 35
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    • For a review of rate studies of LDA-mediated reactions, see
    • For a review of rate studies of LDA-mediated reactions, see: Collum, D. B.; McNeil, A. J.; Ramirez, A. Angew. Chem., Int. Ed. 2007, 46, 3002.
    • (2007) Angew. Chem., Int. Ed , vol.46 , pp. 3002
    • Collum, D.B.1    McNeil, A.J.2    Ramirez, A.3
  • 36
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    • We define the idealized rate law as that obtained by rounding the observed reaction orders to the nearest rational order
    • We define the idealized rate law as that obtained by rounding the observed reaction orders to the nearest rational order.
  • 37
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    • and references cited therein
    • Ma, Y.; Collum, D. B. J. Am. Chem. Soc. 2007, 129, 14818, and references cited therein.
    • (2007) J. Am. Chem. Soc , vol.129 , pp. 14818
    • Ma, Y.1    Collum, D.B.2
  • 38
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    • For leading references and discussion of high-coordinate lithium amides, see ref 20
    • For leading references and discussion of high-coordinate lithium amides, see ref 20.
  • 48
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    • 5 due to the especially large kinetic isotope effect on the metalation.
    • 5 due to the especially large kinetic isotope effect on the metalation.
  • 49
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    • It has been suggested that the n-BuLi adduct of pyridine can reduce pyridine by extruding lithium hydride, a Clegg, W, Dunbar, L, Horsburgh, L; Mulvey, R. E. Angew. Chem, Int. Ed. Engl. 1996, 35, 753
    • It has been suggested that the n-BuLi adduct of pyridine can reduce pyridine by extruding lithium hydride. (a) Clegg, W.; Dunbar, L.; Horsburgh, L; Mulvey, R. E. Angew. Chem., Int. Ed. Engl. 1996, 35, 753.
  • 50
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    • obsdt) showed some discrepancies (Supporting Information), yet a fit to a nonlinear Noyes equation (ref 26b) to obtain the order by best-fit methods revealed an order of 1.0.
    • obsdt) showed some discrepancies (Supporting Information), yet a fit to a nonlinear Noyes equation (ref 26b) to obtain the order by best-fit methods revealed an order of 1.0.
  • 52
    • 58049203362 scopus 로고    scopus 로고
    • obsd for the decay of 5 shows a minor (50%) rise with a 3-fold decrease in THF concentration.
    • obsd for the decay of 5 shows a minor (50%) rise with a 3-fold decrease in THF concentration.
  • 53
    • 58049197325 scopus 로고    scopus 로고
    • The crossover described in Scheme 3 occurs at substantially lower temperatures than the rearrangement to provide 10. As expected, analogous crossover is observed in 10.
    • The crossover described in Scheme 3 occurs at substantially lower temperatures than the rearrangement to provide 10. As expected, analogous crossover is observed in 10.
  • 54
    • 58049217940 scopus 로고    scopus 로고
    • We have never observed [6Li]LiF by NMR spectroscopy. This may derive from a very low solubility
    • 6Li]LiF by NMR spectroscopy. This may derive from a very low solubility.
  • 61
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    • Crystal structures of amidinolithiums: Aharonovich, S.; Kapon, M.; Botoshanski, M.; Eisen, M. S. Organometallics 2008, 27, 1869.
    • Crystal structures of amidinolithiums: Aharonovich, S.; Kapon, M.; Botoshanski, M.; Eisen, M. S. Organometallics 2008, 27, 1869.
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    • 15N are 1 and 1/2, respectively.
    • 15N are 1 and 1/2, respectively.
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    • Dissolving the yellow solid with added N,N,N′, N′-tetramethylethylene-diamine (TMEDA) resulted in very complex mixtures. We suspect that TMEDA mediates reversal of the 1,4-addition, allowing other reactions to occur
    • Dissolving the yellow solid with added N,N,N′, N′-tetramethylethylene-diamine (TMEDA) resulted in very complex mixtures. We suspect that TMEDA mediates reversal of the 1,4-addition, allowing other reactions to occur.
  • 77
    • 58049199617 scopus 로고    scopus 로고
    • By contrast, the relatively weak acid hexamethyldisilazane converts dimer 5 to picoline 1.
    • By contrast, the relatively weak acid hexamethyldisilazane converts dimer 5 to picoline 1.
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    • Also see ref 9
    • (i) Also see ref 9.
  • 100
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    • Mixed condensation of heteroaryllithiums with heteroarenes: (a) Gros, P.; Fort, Y J. Chem. Soc., Perkin Trans. 1 1998, 3515.
    • Mixed condensation of heteroaryllithiums with heteroarenes: (a) Gros, P.; Fort, Y J. Chem. Soc., Perkin Trans. 1 1998, 3515.
  • 112
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    • An alternative radical mechanism for the dimerization of pyridine has been proposed ref 48g
    • An alternative radical mechanism for the dimerization of pyridine has been proposed (ref 48g).
  • 117
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    • Alkylations of 3-picoline proceed in high yield. See, for example: (a) Gedig, T.; Dettner, K.; Seifert, K. Tetrahedron 2007, 63, 2670.
    • Alkylations of 3-picoline proceed in high yield. See, for example: (a) Gedig, T.; Dettner, K.; Seifert, K. Tetrahedron 2007, 63, 2670.
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    • There are discussions of reversible radical-based dimerizations of heteroaromatics: Shimoishimi, H.; Tero-Kubota, S.; Ikegami, Y. Bull. Chem. Soc. Jpn. 1985, 58, 553.
    • There are discussions of reversible radical-based dimerizations of heteroaromatics: Shimoishimi, H.; Tero-Kubota, S.; Ikegami, Y. Bull. Chem. Soc. Jpn. 1985, 58, 553.
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  • 133
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    • Precipitation occurs below 3.9 M THF.
    • Precipitation occurs below 3.9 M THF.
  • 134
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    • obsdt).
    • obsdt).


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.