594-34-3Relevant articles and documents
REACTION OF ACETYLENIC AND VINYLIC ORGANOLITHIUM REAGENTS WITH TRIETHOXYCARBENIUM TETRAFLUOROBORATE: PREPARATION OF α-ACETYLENIC AND α-ETHYLENIC TRIETHYL ORTHOCARBOXYLATES
Picotin, G.,Miginiac, Ph.
, p. 249 - 254 (1987)
Acetylenic and vinylic liyhium derivatives react with triethoxycarbenium tetrafluoroborate to give α-unsaturated triethyl orthocarboxylates.
The reaction of bis(trifluoromethyl)amino-oxyl with t-butyl bromide, t-butyl chloride, 2,2-dichloropropane, 2-chloro-2-phenylpropane and t-butyl acetate
Connelly, Gregory D.,Tipping, Anthony E.
, p. 83 - 92 (2007/10/02)
Reaction of the oxyl (CF3)2NO(.) (1) with t-butyl bromide (c. 2:1 molar ratio) at room temperature results in initial hydrogen abstraction to give the hydroxylamine (CF3)2NOH (3) and the radical (.)CH2CMe2Br (17) which (i) couples with oxyl 1 to afford the compound (CF3)2NOCH2CMe2Br (6) (33.5percent) and (ii) eliminates a bromine atom to give the alkene CH2=CMe2.Addition of oxyl 1 and bromine to the alkene affords the adducts (CF3)2NOCH2CMe2ON(CF3)2 (4) (10percent) and CH2BrCMe2Br (8) (26.5percent), respectively, while allylic hydrogen abstraction from the alkene leads to the compounds 2CMeON(CF3)2 (5) (10percent) and (CF3)2NOCH2CMeCH2Br (7) (15.5percent).Reaction with t-butyl chloride is more complex and gives a number of unidentified products together with the compounds 4 (37percent), 5 (8percent) and (CF3)2NOCH2CMeCH2Cl (9) (3.5percent) formed by an analogous reaction pathway, although the large amount of hydrogen chloride (61percent) isolated indicates that hydrogen abstraction by chlorine atoms competes with abstraction by oxyl 1.With 2,2-dichloropropane, reaction with the oxyl 1 is slow (even at 70-80 deg C) and gives mainly hydrogen chloride, hydroxylamine 3 (32percent), the substitution product (CF3)2NOCH2CCl2CH3 (10) (42percent) and the 2:1 adduct of oxyl 1 and the alkene CH2=CMeCl, i.e. (CF3)2NOCH2CMeClON(CF3)2 (11) (24percent).In contrast, reaction involving 2-chloro-2-phenylpropane is facile at room temperature and affords hydrogen chloride (97.5percent), hydroxylamine 3 (12.5percent) and the 2:1 adduct (CF3)2NOCH2CMePhON(CF3)2 (12) (78percent) of oxyl 1 and the alkene CH2=CMePh.Treatment of t-butyl acetate with oxyl 1 gives hydroxylamine 3 (49percent), the oxadiazapentane (CF3)2NON(CF3)2 (2) (9percent) and the compounds (CF3)2NOCH2CMe2OAc (14) (36percent), 2CHCMe2OAc (15) (15percent) and (CF3)2NO2CCMe2OAc (16) (40percent) formed via successive oxyl 1 attack on a methyl group.In these reactions, compounds arising via a 1,2-shift of bromine, chlorine or acetate were not detected in the products.
Synthesis of the stereoisomers of a novel antibacterial agent and interpretation of their relative activities in terms of a theoretical model of the penicillin receptor
Wolfe,Zhang,Johnston,Kim
, p. 1066 - 1075 (2007/10/02)
2,2-Dimethyl-3-(2'-hydroxypropyl)-5-carboxy-Δ3-1,4-thiazine (1) is a designed antibacterial agent. Based on an analysis of how penicillin complexes to and reacts with a model of a penicillin-binding protein, 1 contains a functional group (C=N) that can react with a serine hydroxyl group of the receptor according to the putative reaction Enz-OH + C=N → Enz-O-C-NH. Compound 1 also contains additional substituents that are designed to position the O-H and C=N groups relative to one another in the enzyme-substrate complex in a geometry that attempts to reproduce the optimum geometry of approach of two such reactants. A most important assumption is that this optimum geometry can be computed ab initio. In a first preparation of 1, (±)-5-methyl-4-hexene-2-ol (2) was converted to the lithium salt of (±)-2-mercapto-2-methyl-5-tert-butyldimethylsiloxy-3-hexanone (7), which was condensed with the N-tert-butoxycarbonyl-D- and L-serine-β-lactones (3). The synthesis was completed by deprotection with formic acid and cyclization in water. The R and S enantiomers of 2 have now been obtained, and the absolute configuration of the alcohol established, by reaction of the R- and S-propylene oxides with an organometallic reagent prepared from β,β-dimethylvinyl bromide. The R alcohol has also been secured by lipase-catalyzed transesterification with trifluoroethyl butyrate, and chemical hydrolysis of the trifluoroethyl ester. The R and S enantiomers of 2 were converted to the R and S enantiomers of 7, and these were condensed with the R and S enantiomers of 3 to yield each of the stereoisomers of the chemically unstable 1 in ca. 95% optically pure form. Antibacterial activity resides in the 5S,8R and 5S,8R isomers. These findings are shown to be consistent with the theoretical model. It is hoped that the stability of the lead structure 1 can be improved, to allow binding experiments with penicillin recognizing enzymes to proceed. 2,2-Dimethyl-3-(2′-hydroxypropyl)-5-carboxy- Δ3-1,4-thiazine (1) is a designed antibacterial agent. Based on an analysis of how penicillin complexes to and reacts with a model of a penicillin-binding protein, 1 contains a functional group (C = N) that can react with a serine hydroxyl group of the receptor according to the putative reaction Enz-OH + C = N → Enz-O-C-NH. Compound 1 also contains additional substituents that are designed to position the O-H and C = N groups relative to one another in the enzyme-substrate complex in a geometry that attempts to reproduce the optimum geometry of approach of two such reactants. A most important assumption is that this optimum geometry can be computed ab initio. In a first preparation of 1, (±)-5-methyl-4-hexene-2-ol (2) was converted to the lithium salt of (±)-2-mercapto-2-methyl-5-tert-butyldimethylsiloxy-3-hex anone (7), which was condensed with the N-tert-butoxycarbonyl-D- and L-serine-β-lactones (3). The synthesis was completed by deprotection with formic acid and cyclization in water. The R and S enantiomers of 2 have now been obtained, and the absolute configuration of the alcohol established, by reaction of the R- and S-propylene oxides with an organometallic reagent prepared from β,β-dimethylvinyl bromide. The R alcohol has also been secured by lipase-catalyzed transesterification with trifluoroethyl butyrate, and chemical hydrolysis of the trifluoroethyl ester. The R and S enantiomers of 2 were converted to the R and S enantiomers of 7, and these were condensed with the R and S enantiomers of 3 to yield each of the stereoisomers of the chemically unstable 1 in ca. 95% optically pure form. Antibacterial activity resides in the 5S,8R and 5S,8S isomers. These findings are shown to be consistent with the theoretical model. It is hoped that the stability of the lead structure 1 can be improved, to allow binding experiments with penicillin recognizing enzymes to proceed.
