Elimination routes

Various criteria have been used to deduce the operation of this mechanism. Since some of them are dependent on comparison with the addition-elimination route, the competition between these two routes will be also discussed. 

Stubbs, 1967) but not always so (Winterfeldt et al., 1966 Harris, 1967 Theron, 1967). The addition of amines, which is dependent on the nature of the amine involved (e.g. Huisgen et at., 1967) was discussed in more detail on pp. 54-58. 

Sometimes the cis isomer reacts via elimination-addition (see (5) below) while the trans isomer reacts via addition-elimination. Since the configuration is retained in the latter route, either addition-elimination for both isomers, or elimination-addition for the cis and addition-elimination for the trans isomer would show overall retention of configuration. 

The difference will also be reflected in the activation parameters. In most cases the activation energy is higher for the elimination-addition route, but examples are known where the differences are small. 

Several of the above criteria are usually used together in order to ascertain the reaction mechanism. The examples below will demonstrate their use, as well as the close relationship between the elimination-addition and the addition-elimination routes. 

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More information has appeared concerning the nature of the side reactions, such as acetoxylation, which occur when certain methylated aromatic hydrocarbons are treated with mixtures prepared from nitric acid and acetic anhydride. Blackstock, Fischer, Richards, Vaughan and Wright have provided excellent evidence in support of a suggested ( 5.3.5) addition-elimination route towards 3,4-dimethylphenyl acetate in the reaction of o-xylene. Two intermediates were isolated, both of which gave rise to 3,4-dimethylphenyl acetate in aqueous acidic media and when subjected to vapour phase chromatography. One was positively identified, by ultraviolet, infra-red, n.m.r., and mass spectrometric studies, as the compound (l). The other was less stable and less well identified, but could be (ll). 

The Hofmann elimination route, of which many versions exist, can be carried out at much lower temperatures in conventional equipment. The PX is generated by a 1,6-Hofmaim elimination of amine from a quaternary ammonium hydroxide in the presence of a base. This route gives yields of 17—19%. Undesired polymeric products can be as high as 80% of the product. In the presence of a polymerization inhibitor, such as phenothiazine, DPXN yields can be increased to 50%. 

For the synthesis of 3-benzothiepin 3,3-dioxide by an elimination route, see Section 2.1.4.1. 

Renal excretion is the most important endosulfan elimination route in humans and animals. Biliary excretion has also been demonstrated to be important in animals. Estimated elimination half-lives ranged between approximately 1 and 7 days in adult humans and animals. Endosulfan can also be eliminated via the breast milk in lactating women and animals, although this is probably a relatively minor elimination route. No studies were located regarding known or suspected differences between children and adults with respect to endosulfan excretion. 

Simpson and Burt have studied the same reactions in the presence of various amounts of ethanol and have plotted graphs of phosphonate (81 R = Ph) and phenyl acetylene produced against moles of alcohol added. Acetylene in the product reached a maximum (around 60%) when two moles of ethanol were added and stayed fairly constant beyond this, which suggests that the attack-on-halogen contribution to the mechanism is approximately 60%. The rest of the reaction presumably follows some other mechanism and the authors suggest the addition-elimination route (79) in view of the isolation of the phosphonate (83) from the reaction of tri(isopropyl) phosphite with the bromoacetylene (84). 

Tsui MTK, Wang WX. 2004. Uptake and elimination routes of inorganic mercury and methyknercury in Daphnia magna. Environ Sci Technol 38 808-816. 

Gabapentin Modulate calcium channels and enhance GABA activity Loading dose Not recommended due to short half-life Maintenance dose 900-3600 mg/day in 3-4 divided doses (doses up to 1 0,000 mg/day have been tolerated) Half-life Not established 5-7 hours (proportional to creatinine clearance) Apparent volume of distribution 0.6-0.8 L/kg Protein binding less than 10% Primary elimination route Renal Drowsiness, sedation Peripheral edema, weight gain... 

Lamotrigine Modulate sodium channels Loading dose Not recommended due to increased risk of rash Maintenance dose 1 50-800 mg/day in 2-3 divided doses. Doses should be initiated and titrated according to the manufacturer s recommendations to reduce the risk of rash Half-life Not established Monotherapy 24 hours Concurrent enzyme inducers 12-15 hours Concurrent enzyme inhibitors 55-60 hours Apparent volume of distribution 1.1 L/kg Protein binding 55% Primary elimination route Hepatic Ataxia, drowsiness, headache, insomnia, sedation Rash... 

Levetiracetam Unknown Loading dose Not recommended due to excessive adverse effects Maintenance dose 1 000-3000 mg/day. Start at 1 000 mg/day and titrate upward as indicated by response Half-life Not established 6-8 hours Apparent volume of distribution 0.5-0.7 L/kg Protein binding less than 10% Primary elimination route 70% renal 30% hepatic Somnolence, dizziness Depression... 

Half-life increases as the dose and serum concentration increases Volume of distribution Adults 0.7 L/kg Children 0.8 L/kg Neonates 1.2 L/kg Protein binding Adults, children 88-92% Neonates 65% Primary elimination route Hepatic (4-8 pmol/L) unbound concentration osteoporosis, rash... 

Studies with rats treated orally with triaryl or trialkyl phosphate esters (which may be found in organophosphate ester hydraulic fluids) indicate that these compounds and their metabolites are readily excreted in the urine, bile, feces and, to a limited extent, in expired air (Kurebayashi et al. 1985 Somkuti and Abou-Donia 1990a Suzuki et al. 1984a Yang et al. 1990). Urinary excretion of metabolites appears to be the predominant elimination route in rats for tri-ort/zo-cresyl phosphate and tri-para-cresyl phosphate, but biliary excretion of parent material and metabolites is also important (Kurebayashi et al. 1985 NTP... 

It is worth noting, that the mechanistic conclusions for the competing 4a — 9a and 4a — 10a routes drawn for the generic catalyst are corroborated for the real catalysts I-IV. The formation of cis-1,2-D VCB and cis,cis-COD is connected with very similar total activation barriers (i.e., relative to the favorable bis(r 3-,vyra) isomer of 4a) for each of the individual catalysts. Furthermore, cis,cis-COD is clearly seen to be the thermodynamically preferred product of the two cyclodimers. The difference in the thermodynamic stability between the [Ni°(ri4-cyclodimer)L] products 9a and 10a is most remarkable for IV with L = P(OPh)3 and amounts to 6.7 kcal moF1 (AG). This confirms the conclusion (cf. Section 4.6.1), that cis,cis-COD is generated as the predominant product along the reductive elimination routes that commence from the bis(ri3) precursor 4a. 

Oxidative coupling via la —> 2a and the reductive elimination routes, that commence from 4a as the precursor, involve different stereoisomers along the most feasible pathway. Accordingly, the conversions of the terminal allylic groups of the [Nin(octadienediyl)L] complex represent indispensable elementary processes. 

Substituted furan formation by an indirect cyclization of 1,4-dicarbonyl derivatives has also been adopted as a key step in the synthesis of 3-oxa-guaianolides. Although 1,4-dicarbonyl compounds have been traditionally considered as the direct precursors for furans, treatment of 1,4-dicarbonyl compounds having a tertiary acetoxy group with p-toluenesulfonic acid leads to only 11% yield of an alkenylfurans as derived from a cyclization/acetoxy-elimination route. The following scheme shows an alternative multi-step conversion of the 1,4-dicarbonyl that leads to a more acceptable yield of the acetoxyfuran . 

Another related bicyclic species (Figure 2.12) has been produced in 20% yield by the reaction of red phosphorus with 1,2-dichlorobenzene on heating in the presence of a Lewis acid catalyst.41 This reaction presumably occurs by an addition-elimination route. 

Finally, (3-bromoacrylate esters react with trialkyl phosphites to provide the unsaturated phosphonates (Equation 3.24), presumably through an addition-elimination route.392... 

The latter elimination route to D-ribal is illustrative of the approach necessary for the preparation of the sensitive furanoid glycals, which are not accessible via the... 

The residues of LAS and ABS detected in the three investigated water streams entering Laguna de Bay could be further reduced by dilution, or biochemical degradation (mainly for LAS). Removal of the surfactants through sorption and precipitation had also been taken into account. This elimination route was particularly important for ABS since many of its derivatives were rather insoluble [26]. 

Elimination routes are also popular in this area of allene hydrocarbon chemistry. For example, hydrosilylation of ynals 159 with triethylsilane in the presence of a rhodium catalyst leads to the a-triethylsilylenals 160 (Scheme 5.23) [64]. 

The efficiency of chirality transfer of chiral 2,3-allenic acids can be much increased by switching the Jt-allylpalladium mechanism to a coordinative cycliza-tion-reductive elimination route (Scheme 16.25) [30]. 

In rats exposed by intratracheal instillation to radiolabeled phenol, elimination was 95% complete after 72 hours, with the primary elimination route being through the urine (Hughes and Hall 1995). Fecal elimination was slower and accounted for less overall. 

Both urinary and fecal excretion of 14C was determined in rats administered an oral dose of 1.2 mg/kg of [14C]-labeled phenol (Edwards et al. 1986). Rats excreted 80.3 11.2% in the urine and 1.8 1.6%inthe feces in 24 hours. In rats exposed orally to radiolabeled phenol, elimination was 95% complete after 72 hours, with the primary elimination route being through the urine (Hughes and Hall 1995). Fecal elimination was slower and less overall. 

Equation lb, b is the defining equation for the addition-elimination route for one-electron transfer between X" and Y. It is important to note that although X-Y is a radical and the overall reaction results in the transfer of a single electron, in the actual electron transfer step an electron pair is shifted rather than a single electron [5]. This means that electron transfer is the consequence of a heterolysis reaction in which the electron pair joining X and Y ends up at... 

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