Azimines, azo-aziridines, 1,2,3-triazoles. Products obtained from the oxidation of N-aminophthalimide in the presence of azo-alkenes

Oxidation of N-aminophthalimide with lead tetraacetate carried out in the presence of an olefinic substrate gives rise to the formation of N-aminoaziridine derivatives [1-5]. It is well accepted that 1,1-disubstituted aminonitrenes can be generated by the oxidation of the corresponding 1,1-disubstituted hydrazines, this reaction has been considered as an aminonitrene cycloaddition to C=C-bonds [1-3]. More recently, Atkinson et al. [4] as well as others [5, 6] have shown and discussed that lead tetraacetate oxidation of N-aminophthalimide and related N-aminoheterocycles involves the N-acetoxyhydrazine intermediate rather than the N-aminonitrene. Regardless of the actual type of intermediate, the "oxidative aminoaziridination" is a convenient method for the synthesis of N-aminoaziridines.

Lead tetraacetate oxidation of N-aminophthalimide in the presence of azo compounds affords phthalimidoazimines, a new class of 1,3-dipolar species [2,3,7].

Azo-alkenes (a,b-unsaturated azo compounds) [8] containing both functional groups aroused our interest to investigate the chemoselectivity of this reaction. To this goal, N-aminophthalimide was oxidized with lead tetraacetate in the presence of several azo-alkenes.

Scheme 1 Oxidation of 1,1-disubstituted hydrazines in the presence of olefins and azo compounds: N-aminoaziridines and azimines

Scheme 2 Azo-alkenes; syntheses

Scheme 3 (E)-b-Phenylazo-stilbene, N-aminophthalimide, lead tetraacetate: 2-phenyl-3-phenylazo-1-phthalimidoaziridine

Scheme 4 (E)-1-phenylazo-1-cyclohexene, N-aminophthalimide, lead tetraacetate: syn-2-phenylazo-1-phthalimidoperhydrocyclohexa[b]aziridine

Scheme 5 (E)-1-phenylazo-1-cyclopentene, N-aminophthalimide, lead tetraacetate: 2-phenyl-2,4,5,6-tetrahydrocyclopenta[d][1,2,3]triazole

Scheme 6 (E)-2-phenylazo-propene, N-aminophthalimide, lead tetraacetate: 4-methyl-2-phenyl-1,2,3-triazole and phthalimide and

(2-phenylhydrazonopropylideneamino)phthalimide [via ene-azimine?]

Scheme 7 3,3,5-Trimethyl-3H-pyrazole, N-aminophthalimide, lead tetraacetate: (E)- and (Z)-3,3,5-trimethyl-3H-pyrazolium-2-(phthalimido)imide and (Z)-3,3,5-trimethyl-3H-pyrazolium-1-(phthalimido)imide

     

References

1. B.V. Ioffe, M.A. Kuznetsov, A.A. Potekhin, "Chemistry of the Organic Hydrazine Derivatives" Khimiya, Leningrad, 1979, p. 224.
2. R.S. Atkinson in "Azides and Nitrenes. Reactivity and Utility" ed. E.F.V. Scriven, Academic Press, New York, 1984, p. 247.
3. M.A. Kuznetsov, B.V. Ioffe, Uspekhi Khimii, 1989, 58, 1271; Russ. Chem. Rev., 1989, 58, 732.
4. R.S. Atkinson, B.J. Kelly, J. Chem. Soc., Chem. Commun. 1987, 1362.
5. D.W. Jones, M. Thorton-Pett, J. Chem. Soc., Perkin Trans. 1 1995, 809.
6. R.S. Atkinson, E. Barker, J. Chem. Soc., Chem. Commun., 1995, 819.
7. A.A. Suvorov, M.A. Kuznetsov, Uspekhi Khimii, 1987, 56, 1324; Russ. Chem. Rev. 1987, 56, 756.
8. J.G. Schantl in Houben-Weyl, "Methoden der Organischen Chemie" vol. E15, Georg Thieme, Stuttgart-New York, 1993, 909.

 

Rapid Synthesis of Pharmaceutical Oxidation Products Using Electrochemistry: A Systematic Study of N-Dealkylation Reactions of Fesoterodine Using a Commercially Available Synthesis Cell

Rapid Synthesis of Pharmaceutical Oxidation Products Using Electrochemistry: A Systematic Study of N-Dealkylation Reactions of Fesoterodine Using a Commercially Available Synthesis Cell

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/op500312e

 

 A new method for the fast and convenient synthesis of pharmaceutical oxidation products is described. Two oxidation products of fesoterodine were electrochemically synthesized, isolated, and characterized. The influence of synthetic operating parameters such as pH, percentage of organic solvent in diluent, initial electrolyte concentration, and substrate concentration on the oxidation product profile was investigated. This synthetic procedure proved to be rapid, clean, and efficient compared to traditional synthetic methods and may be particularly useful for generating milligram quantities of reference samples of degradation products used as markers in chromatographic methods.

 

ORGANIC SPECTROSCOPY INTERNATIONAL

ORGANIC SPECTROSCOPY INTERNATIONAL:



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Methyl 6-nitro-2-norbornene-5-carboxylate

Methyl (E)-3-nitroacrylate is a reactive dienophile in the Diels-Alder reaction. With cyclopentadiene it gives the corresponding adduct, methyl 6-nitro-2-norbornene-5-carboxylate, in 43% yield in refluxing benzene⁹ or in quantitive yield in ether at 0°,¹⁰ as shown below. The adduct was shown by NMR analysis to consist of an 86 : 14 mixture of endo- : exo-nitro stereoisomers, which could not be separated by crystallization.¹⁰

METHYL (E)-3-NITROACRYLATE

[2-Propenoic acid, 3-nitro-, methyl ester (E)-]

¹H NMR (60 MHz, CDCl₃): δ 3.8 (s, 3H, OCH₃), 6.95 (d, J = 14 hz, 1H, =CHNO₂-), 7.55 (d, J = 14 Hz, 1H, =CHNO₂): IR (CCl₄): cm.⁻¹ 3100 s, 3000 m, 2950 s, 2880 m (all CH), 1720 s (C=O), 1640 ms (C=C), 1530 s and 1350 s (NO₂).

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References 

1. N. F. Blom, D. M. F. Edwards, J. S. Field, and J. P. Michael, J. Chem. Soc. Chem. Commun., 1240 (1980).

Drug Patents International

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Making Heterocycles Behave In C-H Activation

 

 

Yu and Dai’s C–H activation method overcomes traditional selectivity limitations, activating the C–H bond next door to a powerful directing group (red bonds).

Making Heterocycles Behave In C-H Activation

Organic Chemistry: Reaction overcomes traditional selectivity issues when applied to complex, druglike molecules.
read at
http://cen.acs.org/articles/92/i46/Making-Heterocycles-Behave-CH-Activation.html

An Efficient, Asymmetric Organocatalyst-mediated Conjugate Addition of Nitroalkanes to Unsaturated Cyclic and Acyclic Systems

An Efficient, Asymmetric Organocatalyst-mediated Conjugate Addition of Nitroalkanes to Unsaturated Cyclic and Acyclic Systems 
C.E.T. Mitchell, S.E. Brenner, J. Garcia-Fortanet and S.V. Ley, Org. Biomol. Chem. 2006, 4, 2039-2049.
http://pubs.rsc.org/en/content/articlelanding/2006/ob/b601877g/unauth#!divAbstract 

5-Pyrrolidin-2-yltetrazole is a versatile organocatalyst for the asymmetric conjugate addition of nitroalkanes to enones. Using this catalyst, this transformation requires short reaction times, tolerates a broad substrate scope, and possibly proceeds via generation of an iminium species.