1876-22-8Relevant academic research and scientific papers
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.
Modification of the amino group of guanosine by methylglyoxal and other α-ketoaldehydes in the presence of hydrogen peroxide
Nukaya,Inaoka,Ishida,Tsuji,Suwa,Wakabayashi,Kosuge
, p. 649 - 653 (1993)
Methylglyoxal is directly mutagenic to Salmonella typhimurium TA100 and its mutagenicity is markedly enhanced in the presence of hydrogen peroxide. We found that methylglyoxal in phosphate buffer was decomposed easily by hydrogen peroxide at room temperature to yield acetic acid and formic acid as major products and diacetyl as a minor product; acetyl radical was detected in the solution by ESR spectroscopy by the use of a spin-trapping reagent, 5,5-dimethyl-1-pyrroline N-oxide. Furthermore, guanosine was converted into N2-acetylguanosine by a combination of methylglyoxal and hydrogen peroxide in 0.1 M phosphate buffers (pH 6.1 to 7.4). This acetylation may be related to the enhancement of methylglyoxal mutagenicity by hydrogen peroxide. Other α-ketoaldehydes such as glyoxal and phenylglyoxal also yielded the corresponding acids and α-dicarbonyls upon reaction with hydrogen peroxide under the same conditions as above. These acids would have been produced through Baeyer-Villiger reaction or coupling of acyl radical with hydroxy radical, and dicarbonyls by dimerization of acyl radicals. In addition, when phenylglyoxal was used, the generation of benzoyl radical and the conversion of guanosine to N2-benzoylguanosine were observed. However, it remains to be established whether the generation of acyl radicals is directly involved in the N-2 acylation of guanosine.
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.
Multi-armed, TEMPO-functionalized unimolecular initiators for starburst dendrimer synthesis via stable free radical polymerization. 1. Tri azo-functionalized unimer
Abdallah, Dalia,Ghani, Mohmad Asri Abd,Cunningham, Michael F.,Kazmaier, Peter M.,Keoshkerian, Barkev,Buncel, Erwin
, p. 1393 - 1402 (2007/10/03)
The synthesis of azobenzene-functionalized multi-armed unimolecular initiators or "unimers" that can be polymerized using styrene or styrenic derivatives via TEMPO (2,2,6,6-tetramethylpiperidenyl-1-oxyl) mediated stable free radical polymerization (SFRP) is described. The unimers are composed of an azobenzene-functionalized core and a TEMPO-modified unit. Homopolymers and copolymers of styrene and acetoxystyrene were synthesized using the mono-and trifunctionalized unimers as initiators under bulk conditions with average molecular weights and polydispersities reported. The studies lay the groundwork for further investigations involving SFRP towards building a light harvesting system by introducing chromophores onto the polymer chains for capturing light and thence transferring it to the azobenzene core.
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.
ESR of new β-phosphorus nitroxides from aldo- and keto-nitrones
Haire, D. Lawrence,Janzen, Edward G.,Hrvoic, Ivan
, p. 767 - 773 (2007/10/03)
This investigation deals mainly with the synthesis of new phosphorus-nitroxide free radicals. Nitroxides with a β -31 P group were synthesized from the aldo-nitrones α-phenyl-N-tert-butylnitrone and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as well as the keto-nitrones 2,5,5-trimethyl-1-pyrroline-N-oxide (2,5,5-M3PO) and 2-phenyl-5,5-dimethyl-1-pyrroline-N-oxide (2-Ph-DMPO). Three different routes were explored. The first two routes involved nitronyl spin trapping of phosphorus-centred radicals generated thermally or photochemically by hydrogen abstraction by tert-butoxyl radicals from di-tert-butyl peroxyoxalate or from photoexcited benzophenone, respectively. The third approach used the addition of phosphorus anions (generated by the strong, hindered base lithium diisopropylamide) to the nitrones and subsequent one-electron oxidation to the corresponding nitroxides. The most novel feature of the work presented here may be the synthesis of β-phosphoranyl [P(OR)4] nitroxide spin adducts. For comparison purposes the related β-phosphityl [P(O)(OR)2] nitroxides were also assembled and characterized by ESR spectroscopy. Copyright
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).
The Role of Aroyloxyl Radicals in the Formation of Solvent-derived Products in Photodecomposition of Diaroyl Peroxides. The Reactivity of Substituted Cyclohexadienyl Radicals and Intermediacy of ipso Intermediates
Takahara, Shigeru,Urano, Tishiyuki,Kitamura, Akihide,Sakuragi, Hirochika,Kikuchi, Osamu,et al
, p. 688 - 697 (2007/10/02)
Photolyses of bis(2-thiophenecarbonyl)peroxide (TPO) in benzene and toluene afforded, among free-radical products, biphenyl and dimethylbiphenyls, respectively, which were solely derived from the aromatic solvents.The yields of biphenyls depended upon the rate with which the radical intermediates were generated from the peroxides in sufficiently high concentrations for their dimerization.Photolyses of TPO and dibenzoyl peroxide in 1,3,5-trimethylbenzene afforded also a solvent-derived products, 2,3',4,5',6-pentamethyldiphenylmethane.Its formation provides clear evidence for participation of cyclohexadienyl radicals bearing the aroyloxyl group on the methyl-substituted ipso carbon atom.
