Anchimeric assistance chlorides

The SEM ester was used to protect a carboxyl group where DCC-mediated esterification caused destruction of the substrate. It was formed from the acid and SEM chloride (THF, 0°, 80% yield) and was removed solvolytically. The ease of removal in this case was attributed to anchimeric assistance by the phosphate group. Normally SEM groups are cleaved by treatment with fluoride ion. Note that in this case the SEM group is removed considerably faster than the phenyl groups from the phosphate. ... 

Within the past several years, we have examined the synthesis and reactions of several classes of polymers related to PECH. We have adopted three simple approaches to the preparation of polymeric substrates more reactive than PECH toward nucleophilic substitution. We have i). removed the 8-branch point by extension of the side chain, ii). replaced the chloride leaving group by a more reactive bromide and iii). replaced the backbone oxygen atom by a sulfur atom that offers substantial anchimeric assistance to nucleophilic... 

Dimethylaminoethane-2-ol (20) is a compound that, by virtue of its nucleophilic center (Me2NH+C2H40), is employed to convert protected segments bound to supports as benzyl esters into acids by transesterification into dimethylaminoethyl esters [C(=0)0C2H4NMe2] that are hydrolyzable by a dimethylformamide-water (1 1) mixture. Compound 20 readily forms esters from acid chlorides. The hydrolysis and esterification are facilitated by anchimeric assistance by the adjacent nitrogen atom (see Section 2.10). The amino alcohol also reacts with dichloromethane. 

FIGURE 8.21 Proposed mechanism for the BOP-Cl-mediated reaction of a carboxylate anion with a methylamino group. Formation of a mixed anhydride is followed by aminolysis that is facilitated by anchimeric assistance provided by the oxygen atom of the ring carbonyl.101 (van der Auwera Anteunis, 1987). BOP-C1 = fcw(2-oxo-3-oxazolidino)phosphinic chloride. 

Alkylhydroxyamoyl chloride, 296 2-Alkylthio 6-methyltetrahydro-pyrans, 21 Amides, 101-162 Amidines, 149-153, 296 Amidoxime, 295 Analgesia,357 Analgesics, 357 Anchimeric assistance, 192 Anhydroryanodol, 265... 

In connection with the methoxy participation, the gas-phase pyrolytic elimination of 4-chloro-1 -butanol was investigated177. The products are tetrahydrofuran, propene, formaldehyde and HCl. It is implied that the OH group provides anchimeric assistance from the fact that, besides formation of the normal unstable dehydrochlorinated intermediate 3-buten-l-ol, a ring-closed product, tetrahydrofuran, was also obtained. The higher rate of chlorobutanol pyrolysis with respect to chlorethanol and ethyl chloride (Table 27) confirmed the participation of the OH group through a five-membered ring in the transition state. 

The homogeneous unimolecular decomposition of o-hydroxy-2-phenvlethyl chloride yielded mainly benzodihydrofuran, HC1 and much less o-hydroxystyrene. The rate was significantly higher than that of phenylethyl chloride and ethyl chloride (Table 28). According to the nature of the product formation and the kinetic data, the OH provided anchimeric assistance in the elimination process. The mechanism proposed is described in equations 87 and 88. 

There is no doubt that the CH3S group is providing anchimeric assistance through the favorable cyclic five-membered transition state. In this respect, the reaction mechanism via an ion-pair intermediate suggested intramolecular solvation of the leaving chloride ion to form only tetrahydrothiophene and CH3C1 (equation 89). 

There is much additional evidence to support the postulate that the effect of neighboring sulfur is due to anchimeric assistance. Cyclohexyl chloride undergoes solvolysis in ethanol-water to yield a mixture of alcohol and ether. As usual for secondary alkyl substrates, reaction is SnI with nucleophilic assistance from the solvent (see Sec. 14.17). A C5H5S— group on the adjacent carbon can speed... 

To test these alternative hypotheses, a tremendous amount of work has been done, by Brown and by others. For example, camphene hydrochloride is known to undergo ethanolysis 6000 times as fast as rer/-butyl chloride, and this had been attributed to anchimeric assistance with formation of a bridged ion. Brown pointed out that the wrong standard for comparison had been chosen. He showed that a number of substituted (3°) cyclopentyl chlorides (examine the structure of camphene hydrochloride closely) also react much faster than rerr-butyl chloride. He attributed these fast reactions—including that of camphene hydrochloride—to relief of steric strain. On ionization, chloride ion is lost and the methyl group on the ap hybridized carbon moves into the plane of the ring four non-bonded interactions thus disappear, two for chlorine and two for methyl. For certain systems at least, it became clear that one need not invoke a nonclassical ion to account for the facts. 

Isolated ratio (cisjtrans) 11.0 the tran -isomer appears to be unstable, presumably because of the ability of nitrogen to anchimerically assist in the loss of chloride in the /ra .v-isomer. ... 

Subsequently the same authors established that the solvolysis of optically active 6,7-dimethoxy-l,2-dimethyl-2-exo-norbornyl chloride or -p-nitrobenzoate is accompanied by anchimeric acceleration as distinct from the unsul tituted analogues 275 and 276 the resulting products are optically active Thus, anchimeric assistance leads to the formation of an unsymmetrical cation which may be the homobenzylic ion 278 while the partial loss of activity is due to the interconversion of enantiomeric ions. The authors have also shown that the accelerating effect of the homopara-methoxyl group is practically the same for the solvolysis in methanol, 50% acetone... 

In one case, pyrolysis of an ester led to anti elimination. The results were explained on the basis of a mechanism incorporating anchimeric assistance Smissman, E. E. Li, J. P. Creese, M. W. /. Org. Chem. 1970,35,1352. Anchimeric assistance was also proposed for a gas phase elimination of hydrogen chloride Hernandez,). A. Chuchani, G. Int. J. Chem. Kinet. 1978,10,923 Chuchani, G. Martin, I. /. Phys. Chem. 1986, 90, 431. 

Thionyl chloride Is highly electrophilic, and converts the alcohol to the corresponding alkyl chloride via an addition-elimination process (with neighbouring group or anchimeric assistance of the SMe group). 

The nucleophilic hydroxyl oxygen of the carboxylic anion, generated by deprotonatlon of the carboxylic acid, undergoes a nucleophilic substitution reaction with the alkyl chloride formed In the previous step (with anchimeric assistance of the SMe group) to give the ester product. 

The halide-catalysed racemization of ( +)-2-methylsulphinylbenzoic acid follows complex kinetics in acid solution, possibly indicating anchimeric assistance by carboxyl. Iodide ion reduction and chloride ion racemization of isopropyl phenyl sulphoxide have been studied in H2SO4 in comparison with HCIO4, and the greater relative rate of racemization in H2SO4 suggests a shift towards general-acid catalysis. Both reactions involve the same intermediate R2S-X (X = Cl or I), but the reduction process is known to be a specific-acid-catalysed reaction. 

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