Participation by ether oxygen (RO-3) in the hydrolysis of sulfonate esters of 2-methoxyethanol and 2-methoxy-2-methyl-1-propanol. Implications regarding the nonlinear ethanol-trifluoroethanol plot for mustard chlorohydrin

Abstract

The lack of scrambling with deuterium-labeled reactants, a nonlinear ethanol-trifluoroethanol plot, and rate acceleration by added thiourea are used to show that sulfonate esters of methoxyethanol (MeOCH2CH2OH) undergo solvent-assisted displacement in a variety of solvents; neighboring group participation by ether oxygen (RO-3 participation) does not occur. This conclusion is in accord with predictions of rate based on the Taft treatment of substituent effects. On the other hand, the branched derivative MeOCMe2CH2OBs reacts with concerted RO-3 participation to give completely rearranged product. Its solvolysis rate is insensitive to added thiourea, the Taft treatment predicts modest anchimeric assistance, and a linear ethanol-trifluoroethanol plot is observed. We discuss the implications of these results relative to the previously observed nonlinear plot for mustard chlorohydrin.In discussing intramolecular nucleophilic assistance by a neighboring group, Winstein found it useful to define solvolytic rate constants in mechanistic terms: kA being the rate constant for anchimerically assisted ionization, ks being the rate constant for nucleophilically assisted displacement by solvent, and kc being the rate constant for the idealized process that involves neither neighboring group nor solvent nucleophilic assistance. In their pioneering studies, Winstein and his co-workers found that oxygen in the five or six position of MeO(CH2)"OBs gave large solvolytic rate enhancements although oxygen in the three or four position slowed solvolysis.1•2 They concluded that participation to form fiveand sixmembered rings was strong, while participation to form threeand four-membered rings was weaker; the RO-3 system was described as a borderline ks-kA system.Recently, Eliel and co-workers have shown RO-4 participation to be absent from the system with = 4.3 However, in branched systems such as PhCH20-and MeOCMe2(CH2)"X ( = 1, 2), Winstein1 and Eliel3 have shown that RO-3 and RO-4 participation can be enhanced relative to direct displacement by solvent. Branching favors neighboring group participation by sterically slowing solvent displacement,4 by stabilizing the cyclic ions,5 and by the Thorpe-Ingold effect.6 Although the branched RO-3 substrate gives complete rearrangement, the RO-4 system gives a variable amount of rearrangement dependent on the number and position of methyl branches and medium effects. Neither study yielded compelling data to confirm significant anchimeric assistance by the neighboring oxygen atom.

Synthesis of Surfactants Based on Pentaerythritol. I. Cationic and Zwitterionic Gemini Surfactants

“…These nucleophilic displacements probably proceed by an S N 2 mechanism, − even though S N 2 displacements of halides and tosylates in neopentyl derivatives are known to occur slowly and mechanisms involving single electron transfer (S RN 1) are often considered for displacement of neopentyl halides, particularly iodides. , It is probable that S N 2 displacements in pentaerythritol systems are faster than those in neopentyl systems because of neighboring group participation as shown in Scheme . Although participation by oxygen through four-membered-ring intermediates does not normally provide significant rate enhancement, − when branching on the intervening atoms is present, significant rate enhancements have been observed. , Dale and Fredriksen suggested that displacements of bromides by alkoxides from 2-bromo-2-methyl-1,3-dibromopropane proceed via four-membered-ring bromonium ion intermediates . We believe that the iodide displacements here follow the S N 2 mechanism both because neighboring group participation is possible and also because the dependency of ease of reaction on the steric bulk of the nucleophile fits what is expected for an S N 2 mechanism.…”

Mechanistic Insights into the Hydrolysis of 2-Chloroethyl Ethyl Sulfide: The Expanded Roles of Sulfonium Salts

“…The topic of mustard (bis(2-chloroethyl)sulfide) hydrolysis reaches back to the work of Hopkins in 1919 . In subsequent years numerous publications exploring this topic have been published. − In spite of all this work, the mechanism of mustard hydrolysis remains elusive. Last year alone, another 105 publications on facets of mustard chemistry were added to ChemAbstracts, and current world events demonstrate the continued relevance of mustard.…”

“…2-Chloroethyl ethyl sulfide yielded only two sulfonium salts and one organic product, greatly simplifying the identification and monitoring of the reaction. Previous work by McManus and co-workers − , using 2-chloroethyl ethyl sulfide or 2-chloroethyl methyl sulfide was primarily focused on probes to assess nucleophilic solvent assistance. The mustards used were often more involved structures meant to examine a particular topic regarding solvent assistance and not necessarily the hydrolysis itself.…”

Competitive RO-6 neighboring group participation and solvent-assisted displacement with 2-(2-methoxyethoxy)ethyl tosylate

“…Geminal dimethyl substitution is said to favor neighboring group participation by operation of the Thorpe-Ingold effect.4 Additionally with 2-OBs, the gem-dimethyl groups stabilize the product of methoxy group migration, i.e., Me2C+-CH2OMe. 3 The previous studies provide the basis for the present work which models the reactivity of simple polyethers like polyethylene glycol) (PEG) sulfonate esters. 5 In this report we have studied the polyether model substrate 3-OTs, which has the opportunity for both and RO-6 participation.…”