1876-22-8Relevant articles and documents
Glutarimidyl Chemistry: Substitution Reactions. Mechanism of "Ziegler Brominations"
Luening, U.,Seshadri, S.,Skell, P. S.
, p. 2071 - 2077 (1986)
Glutarimidyl (G-radical) radicals are generated in liquid-phase chain reactions by halogen atom abstractions from N-haloglutarimides by alkyl radicals.These reactions are carried out in the presence of small amounts of alkenes which act as halogen scavengers to eliminate halogen atom chains.The distinguishing characteristics of glutarimidyl radicals are (1) a constant hydrogen abstraction ratio (kneo-C5H12/kCH2Cl2)H = 5.3 at 15 deg C, over a wide range of reaction conditions, (2) no ring opening with glutarimidyls lacking 2-substituents, and (3) ring opening to make 4-bromoalkanoyl isocyanates with N-bromoglutarimides substituted by methyl(s) in the 2-position.Glutarimidyl radical hydrogen abstraction selectivities are characterized by early transition states for a variety of substrates, with behavior similar to that shown by chlorine atoms and by succinimidyl radicals.With adequate scavenging of bromine, using 1,3-butadiene or norbornene, brominations of benzylic hydrogen take place with the G-radical carrier, with selectivities similar to those obtained with Cl-radical, thus providing definitive proof that "Ziegler brominations" are not attributable to G-radical hydrogen abstractions.
A Short Synthesis of (+)-Brefeldin C through Enantioselective Radical Hydroalkynylation
Gn?gi, Lars,Martz, Severin Vital,Meyer, Daniel,Sch?rer, Robin Marc,Renaud, Philippe
supporting information, p. 11646 - 11649 (2019/08/30)
A very concise total synthesis of (+)-brefeldin C starting from 2-furanylcyclopentene is described. This approach is based on an unprecedented enantioselective radical hydroalkynylation process to introduce the two cyclopentane stereocenters in a single step. The use of a furan substituent allows a high trans diastereoselectivity to be achieved during the radical process and it contains the four carbon atoms C1–C4 of the natural product in an oxidation state closely related to the one of the target molecule. The eight-step synthesis requires six product purifications and it provides (+)-brefeldin C in 18 % overall yield.
Oxidation of HMG-CoA reductase inhibitors by tert-butoxyl and 1,1-diphenyl-2-picrylhydrazyl radicals: Model reactions for predicting oxidatively sensitive compounds during preformulation
Karki, Shyam B.,Treemaneekarn, Varaporn,Kaufman, Michael J.
, p. 1518 - 1524 (2007/10/03)
Hydrogen atom abstraction rate constants for the reaction of tert-butoxyl and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical with the HMG-CoA reductase inhibitors lovastatin, simvastatin, and statins I-IV were measured. This series of dienecontaining drugs is known to be prone to oxidation. The tert-butoxyl radical was generated by the thermolysis of di-tert-butylperoxyoxalate at 40 °C. A competitive kinetic method was used to determine the relative rate of hydrogen atom abstraction by tertbutoxyl radical to β-scission. The absolute rate constants were calculated using the experimentally determined product ratios of t-butanol to acetone and the known rate of β-scission of tert-butoxyl radical. The rate constants for the reaction with DPPH radical were measured spectrophotometrically by monitoring the loss of DPPH radical as a function of substrate concentration. The rate constants correlate well with the structure of the molecules studied. These kinetic techniques allow for oxidatively sensitive compounds to be identified early in the drug development cycle. The tert-butoxyl radical, a strong hydrogen atom abstractor, is representative of the hydroxyl (· OH) and alkoxyl (· OR) radicals; In contrast the DPPH radical, a much weaker radical, is a good kinetic model for hydroperoxyl (· OOH) and peroxyl (· OOR) radicals. These kinetic methods can be used to quantitatively assess the lability of drug candidates towards reaction with oxygen-centered radicals at an early stage of development and facilitate the design of inhibiting strategies. (C) 2000 Wiley-Liss, Inc.
Spin trapping chemistry of iminyl free radicals
Janzen, Edward G.,Nutter, Dale E.
, p. 131 - 140 (2007/10/03)
The iminyl radicals formed from hydrogen atom abstraction between tert-butoxyl radicals and benzylidene-N-alkyl-or N-arylamines were trapped by 2-methyl-2-nitrosopropane and investigated by EPR spectroscopy. The compounds investigated were benzylidene N-methyl, ethyl, 1-propyl, 1-butyl, 2-methylpropyl, 1-methylethyl, 1-methylpropyl, 1-ethylpropyl, 1-methylbutyl and cyclohexyl derivative and also benzylidene N-phenyl, 4-tolyl, 4-fluorophenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-nitrophenyl and 4-trifluoromethylphenyl derivatives. In every case the iminyl nitroxide (aminoxyl) was produced in benzene at room temperature. The nitrogen hyperfine splitting constants were in the ranges 3.39-3.56 and 9.68-9.77 G for the iminyl and nitroxyl nitrogens, respectively, for the benzylidene-N-alkylamines and 3.60-3.77 and 8.45-9.15 G for the iminyl and nitroxyl nitrogens, respectively, for the benzylidene-N-arylamines. Very little evidence was found for hydrogen atom abstraction from the alkyl groups attached to the imine function. The absolute rate constant for hydrogen atom abstraction of the iminyl hydrogen was estimated to be 1.2 × 104 M-1 s-1 based on competitive experiments with addition of tert-butoxyl radicals to 2-methyl-2-nitrosopropane (1.5 × 106 M-1 s-1). This value is considerably slower than that for benzaldehyde (2.4 × 107 M-1 s-1).
