No abstract

The reaction of dl-and weio-2,3-dibromobutanes with tri-n-butyltin hydride gives 2-butenes as major products by a free-radical chain-debromination reaction in which anti elimination predominates. The stereospecificity increases with increased organotin hydride concentration and with decreasing temperature. The isomeric 2,3-dichlorobutanes give simple reduction as the major reaction with tri-n-butyltin hydride, and the same proportions of cis-and trans-butenes are formed from each isomeric chloride. 1,2-Dibromo-l -deuteriohexane gives preferred anti elimination, but the 2,3-dibromosuccinates and 1,2-dibromo-l ,2-dichloroethanes give nonspecific debrominations. 1 -Bromo-1 -phenyl-2-chloroethane reacts more slowly with tri-n-butyltin radicals than does 1,2-dibromo-1 -diphenylethane; m7/!ro-2-bromo-3-chlorobutane reacts more slowly than does meso-2,3-dibromobutane. These results are consistent with a reaction scheme involving open and halogen-bridged free-radical intermediates. The bridged radicals are destabilized by chlorine and by carbethoxy groups in the a positions.An investigation of the scope of the reaction of alkyl halides with organotin hydrides has revealed that geminal polyhalides undergo stepwise reduction to alkanes.1 On the other hand, propylene and mesostilbene dibromides do not undergo normal reduction to hydrocarbon upon reaction with tri-n-butyltin hydride. lb The major products of the reaction of 1 mol of the vicinal dibromide with 2 mol of the hydride were hydrogen, olefin, and tri-n-butyltin bromide.Since it had been demonstrated that the reduction of simple alkyl halides with organotin hydrides proceeds by a free radical chain mechanism,2 345it was of interest to determine some characteristics of this elimination, which might also be a free-radical process.Ionic eliminations have been extensively studied and results have been reviewed.3-5 Free-radical eliminations have received far less systematic investigation as shown in a recent summary by Kampmeier and coworkers.6 78910Such processes are generally regarded as involving formation of free radicals from which ß substituents can be lost, in turn, as free radicals. This is tantamount to reversibility in the first step of a freeradical addition to an olefin, a process which can be conveniently used as a means for isomerization of olefins, eq 1. Halogen atoms,7,8 thiyl radicals,9,10 and organotin radicals11 can function as X• in eq 1. The intermediate radical 1 may be formed from a saturated molecule by hydrogen abstraction as in the photochlorination of bromocyclopentane,12 by the reaction(1) (a) H. G.

Little is known about the metabolism of acetylenic (C&tbd1;C) compounds commonly used in the formulation of pesticides. To better understand the in vivo reactivity of this bond, we examined the metabolism of propargyl alcohol (PA), 2-propyn-1-ol, used extensively in the chemical industry. [1,2,3-(13)C, 2,3-(14)C]PA was administered orally to male Sprague-Dawley rats. Approximately 56% of the dose was excreted in urine by 96 h. Major metabolites were characterized, directly, in the whole urine by one- and two-dimensional (13)C NMR. To determine the complete structures of metabolites of PA, rat urine was also subjected to TLC followed by purification of separated TLC bands on HPLC. The purified metabolites were identified by (13)C NMR and mass spectrometry and by comparison with available synthetic standards. The proposed metabolic pathway involves oxidation of propargyl alcohol to 2-propynoic acid and further detoxification via glutathione conjugation to yield as final products: 3, 3-bis[(2-(acetylamino)-2-carboxyethyl)thio]-1-propanol, 3-(carboxymethylthio)-2-propenoic acid, 3-(methylsulfinyl)-2-(methylthio)-2-propenoic acid, 3-[[2-(acetylamino)-2-carboxyethyl]thio]-3-[(2-amino-2-carboxyethyl)t hio]-1-propanol and 3-[[2-(acetylamino)-2-carboxyethyl]sulfinyl]-3-[2-(acetylamino)-2-car boxyethyl]thio]-1-propanol. These unique metabolites have not been reported previously and represent the first example of multiple glutathione additions to the carbon-carbon triple bond.

The urinary metabolites of [14C]quizalofop-P-tefuryl, (JZ,S)-tetrahydrofurfuryl (R)-2-[4- [(6-chloro-2quinoxalinyl)oxy]phenoxy]propanoate, were identified. A lactating goat received three consecutive daily oral doses of quizalofop-P-tefuryl, equivalent to 330 ppm in the daily diet. The animal was sacrificed 24 h after the last administration. A major route of elimination was found to be via the urine, where two metabolites were observed by HPLC. The major metabolite was identified by mass and NMR spectrometry as quizalofop, a compound resulting from hydrolysis of the tetrahydrofurfuryl alcohol moiety of quizalofop-P-tefuryl. The minor metabolite was more polar than quizalofop, and its molecular weight was 16 amu higher than that of quizalofop. This metabolite was identified as a hydroxy derivative of quizalofop. Cochromatographic comparison of the minor metabolite with synthetic (R)-2-[4-[(6-chloro-3-hydroxy-2-quinoxalinyl)oxy] phenoxy] propanoic acid, prepared in three steps, revealed that hydroxylation had occurred at the 3-position of the quinoxaline ring.

Species differences in the metabolism of acetylenic compounds commonly used in the formulation of pharmaceuticals and pesticides have not been investigated. To better understand the in vivo reactivity of this bond, the metabolism of propargyl alcohol (PA), 2-propyn-1-ol, was examined in rats and mice. An earlier study (Banijamali, A. R.; Xu, Y.; Strunk, R. J.; Gay, M. H.; Ellis, M. C.; Putterman, G. J. J. Agric. Food Chem. 1999, 47, 1717-1729) in rats revealed that PA undergoes extensive metabolism primarily via glutathione conjugation. The current research describes the metabolism of PA in CD-1 mice and compares results for the mice to those obtained for rats. [1,2,3-(13)C;2,3-(14)C]PA was administered orally to the mice. Approximately 60% of the dose was excreted in urine by 96 h. Metabolites were identified, directly, in whole urine by 1- and 2-D (13)C NMR and HPLC/MS and by comparison with the available reference compounds. The proposed metabolic pathway involves glucuronide conjugation of PA to form 2-propyn-1-ol-glucuronide as well as oxidation of PA to the proposed intermediate 2-propynal. The aldehyde undergoes conjugation with glutathione followed by further metabolism to yield as final products 3,3-bis[(2-acetylamino-2-carboxyethyl)thio]-1-propanol, 3-[(2-acetylamino-2-carboxyethyl)thio]-3-[(2-amino-2-carboxyethyl)thi o]-1-propanol, 3,3-bis[(2-amino-2-carboxyethyl)thio]-1-propanol, 3-[(2-amino-2-carboxyethyl)thio]-2-propenoic acid, and 3-[(2-formylamino-2-carboxyethyl)thio]-2-propenoic acid. A small portion of 2-propynal is also oxidized to result in the excretion of 2-propynoic acid. On the basis of urinary metabolite data, qualitative and quantitative differences are noted between rats and mice in the formation of the glucuronide conjugate of PA and in the formation of 2-propynoic acid and metabolites derived from glutathione. These metabolites represent further variation on glutathione metabolism following its addition to the carbon-carbon triple bond compared to those described for the rat.