Intermediates substitution

Substitution reactions by the ionization mechanism proceed very slowly on a-halo derivatives of ketones, aldehydes, acids, esters, nitriles, and related compounds. As discussed on p. 284, such substituents destabilize a carbocation intermediate. Substitution by the direct displacement mechanism, however, proceed especially readily in these systems. Table S.IS indicates some representative relative rate accelerations. Steric effects be responsible for part of the observed acceleration, since an sfp- caibon, such as in a carbonyl group, will provide less steric resistance to tiie incoming nucleophile than an alkyl group. The major effect is believed to be electronic. The adjacent n-LUMO of the carbonyl group can interact with the electnai density that is built up at the pentacoordinate carbon. This can be described in resonance terminology as a contribution flom an enolate-like stmeture to tiie transition state. In MO terminology,.the low-lying LUMO has a... 

Substitution of more complex acids for formic acid in the last step of the purine synthesis will afford intermediates substituted on the imidazole carbon atom. Thus, condensation of diaminouracyl, 12, with phenylacetic acid gives the benzylated... 

Bromo-j3-nitrostyrene and triphenylphosphine in dry benzene gave the phosphonium bromide (47). Using methanol as the solvent, the rearranged product (48) was formed, possibly via an azirine intermediate. Substituted -bromo-/3-nitrostyrenes yield the phosphoranes (49) and a phosphonium salt. When the aryl group is electron-donating, the reaction follows a different course to form the styrene (50) by initial attack of the phosphine on halogen. 

These sequential steps generate the intermediate substituted tetrahydrofuran-2-ol, which is converted in the second sequence into the final product shown. 

The preparation in good yield of (3-mercaptoethylphosphines has been accomplished by the free radical-induced addition of primary and secondary phosphines across the olefinic linkage of 2-(vinylthio)tetrahydropyran.446 The target materials were isolated by hydrolysis of the intermediate substituted thiotetrahydropyran. 

The intermediate substituted benzal chloride is hydrolysed in the presence of alkali to produce salicylaldehyde. 

Electrochemical oxidation of pentafluoroaniline (1) at a platinum anode at a potential of +1.5 to 1.6 V (vs SCE) using an acctonc/water/potassium acetate electrolyte leads to decafluoro-diphenyldiazene (3) and octafluorophenazine (2) in 18% and 6% yield, respectively. The phenazine heterocycle is formed by a sequence of oxidation/substitution steps in which nitrogen radical intermediates substitute fluorine atoms. The low yield in this reaction is due to a laborious workup.203 204... 

A proton on a y-carbon may be eliminated in competition with a proton on the a-carbon, and subsequent addition of the nucleophile to the central carbon atom of the intermediate substituted allene (189) would result in an overall substitution (equation 18). In this j8,y-elimination-... 

In the addition-elimination routes, either via a carbanionic intermediate (I) or via a neutral adduct (II), the anionic nucleophile Nu or the neutral nucleophile NuH attacks the /3-carbon with the expulsion of X. In the a,/8-route (IV), the /9,/3-route (VI) and the /8, y- elimination-addition routes (VII), HX is eliminated in the initial step, and the nucleophile and hydrogen are then added to the intermediates. Substitution occurs also by heterolytic C—X bond cleavage in an SN1 process (X). Initial prototropy followed by substitution can also give vinylic substitution products (XII, XIV), as well as two consecutive Sn2 reactions (XV) where the leaving group leaves from an allylic position. 

In the case of terpyridine and acridine derivatives, the bis(methylamines) are the most convenient intermediates. Substituted 4/-phenyl-2,2/ 6/,2"-terpyridines were prepared by reacting (ii)-propenons and iV-[2-(pyrid-2 -yl)-2-o octln l p ridinium iodide with ammonium acetate in acetic acid or in methanol. The terminal pyridine moieties were oxidized with 3-chloroperbenzoic acid to iV, A" -dio idcs followed by modified Reisserty-Henze reaction to obtain 6,6"-dicarbonitriles. The bis(methylamines) were obtained by reduction of the 6,6"-dicarbonitriles withborane (scheme 8 (Mukkala et al., 1993)). 

Kinetically inert square-planar complexes are found by d8 low-spin ions, particularly Pt2+. Ligand substitution is associative and correlated with the ease of forming a five coordinate transition state (or intermediate). Substitution is much faster with Ni2+ where five-coordinate complexes such as [Ni(CN)5]3- are more stable than for Pt. For a given metal, the rate of substitution is controlled by ... 

Overall yield, including reduction of the intermediate -substituted aldehyde esters and laetonization. 

Substitution by Alkyls of Zinc, Mercury, and Aluminum. The reaction of alkyls of zinc with ethyl silicate or silicon tetrachloride was the first to be used for the preparation of organosilicon compounds. During the period 1863 to 1880 Friedel and Crafts and later Ladenburg employed zinc dimethyl and zinc diethyl to prepare the corresponding alkyls of silicon and many of the intermediate substitution products as well. The reactions were conducted in sealed tubes heated to about 160° and were of a straightforward metathetical type ... 

The fact that cation-stabilizing R3 groups facilitate the reaction (R3 = NR2 > OR > CH3 > CP ) supports the postulation of a cationic intermediate. Substitution at the allylic C-2 position prevents the rearrangement either by steric repulsion or by the more facile Pd H elimination from the tertiary palladium intermediate. 

In order to treat influenza infections, the development of neuraminidase inhibitors is required. The currently available compounds are not potent enough, and they have a number of side effects. The stereoselective total synthesis of one potent inhibitor, BXC-1812 (RWJ-270201), was achieved by M.J. Muller and co-workers. The key intermediate substituted nitromethane was prepared via a Pd-catalyzed allylation of nitromethane under basic conditions. The transformation of this nitroalkane to the corresponding carboxylic acid methyl ester was carried out in two steps. The Nef reaction was conducted in DMF instead of the usual DMSO because DMSO as the solvent caused extensive epimerization of the product. The initially formed carboxylic acid was then esterified. 

Relatively few significant papers appeared on oxepine systems or fused derivatives. Rearrangement processes were commonly involved in their synthesis. For example, treatment of 89 with n-BuLi and then methanesulfonyl chloride afforded the oxepine 90 as a dark red solid in good yield via rearrangement of the intermediate substituted benzene oxide derivative <05TL3221>. 

Clusters substituted with water or water fragments are known. The 58-electron anion [Re4(/ -H)3(/ 3-H)(CO)i2] (Fig. 8) reacts reversibly with a water molecule, which is probably coordinated as a bridging ligand. This complex is unstable above 270 K and gives a derivative with a triply bridging OFF, presumably via a tetrahy-dridic intermediate substituted with a water molecule coordinated to only one metal center. ... 

Earlier work on the reactions of vinyl halides with tertiary phosphine platinum(0) compounds showed that complexes such as [Pt( y -vinyl halide)(PPh3)2] are formed initially, and the kinetics and mechanism of the oxidative addition (isomerization) were examined. Corresponding work on halogenoalkynes has now been carried out. Thus when c/5 -[PtCl2(PPh3)2] is reduced with hydrazine in the presence of PhC=CX (X =Br or I") the product obtained is [PtX(C= CPhXPPhs). ]. However, with PhC = Cl the intermediate substitution product [Pt(jj -PhC CCl)(PPh3)2] could be isolated and its internal oxidative addition examined mechanistically [see equation (8)]. 

The precipitation of [V(CO) Arene] [V(CO)g] in the reaction medium is probably preceded by the formation of a soluble substitution product of V(CO)g. In view of the known (1,6) oxydising properties of hexacarbonylvanadium, the formation of the final ionic compounds clearly involves an oxidation-reduction step by a second molecule of V(CO)g. The nature of the intermediate substitution product will be discussed. 

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