I am under the impression that in a mixture of hydroxide ions, haloalkanes, water, and ethanol, under low temperatures, nucleophilic substitution will occur predominantly, with small amounts of elimination.

When no water is present and the solution is heated, elimination will occur to a greater degree. Is it possible for nucleophilic substitution to occur when no water is present as all?

Thanks a lot.


Keeping other parameters fixed, an elevated temperature may enhance the rate of elimination such the product of elimination is more dominant than the one by substitution. But there is not a "critical temperature" above which only elimination will occur every time, rather than the structure of the substrate and of the reagent equally influence this.

For the other part, transesterifications as one example work better in absence of water. See, the oxygen present in the water molecule, with highly concentrated electron density, it may act as a nucleophile, too -- a rather hard one (HASB princible) -- leading to parasitic side reactions.

  • $\begingroup$ So is it possible for substitution reactions, say with hydroxide ions, to occur in the complete absence of water? $\endgroup$ Mar 1 '17 at 16:55
  • $\begingroup$ @BenjaminRoger-Newsome Methoxymethylations, as one example to form ethers (cf. Organic Synthesis, 2007, 84, 102, DOI: 10.15227/orgsyn.084.0102) are performed in absence of water. The "standard" Williamson ether synthesis is the reaction of an alkylbromide on an alcoholate, the later prepared in situ by the action of metallic sodium on the alcohol (sometimes the latter is used at the same time as solvent of reaction) -- the presence of water would dangerously rapid yield NaOH, hydrogen gas and liberation of a lot of heat. $\endgroup$
    – Buttonwood
    Mar 1 '17 at 17:06
  • $\begingroup$ Ok, thank you. In the case of hydroxide ions acting as nucleophiles or as bases, is it possible for the hydroxide ion to act as a nucleophile in the absence of water? $\endgroup$ Mar 1 '17 at 17:08
  • $\begingroup$ @BenjaminRogers-Newsome An other classic is the Finkelsteijn exchange of halogenated alkanes in acetone; sometimes "Finkelstein like" exchanges (mesylates, tosylates, etc.) are added to this type of reaction, too. $\endgroup$
    – Buttonwood
    Mar 1 '17 at 17:09
  • $\begingroup$ Nucleophilic / basic ... is a question of definition. And each time, ask the question by stating the potential substrate and its structure, too. Lewis bases posses by definition a free electron pair and may indeed react as nucleophile, too. On the other side, 2,6-lutidine, to mention just one organic base frequently used in the (small scale) research lab is, by means of its sterical hinderance, no longer a nucleophile. $\endgroup$
    – Buttonwood
    Mar 1 '17 at 17:18

Whether nucleophilic substitution occurs depends primarily on the nature of the potential nucleophile, the potential leaving group and the molecule potentially attacked nucleophilicly. Secondary effects are caused by the solvend in question.

Most importantly to answer your question, many nucleophilic substitutions are performed in the absence of water since water itself is a nucleophile and would interfere. Here are just a few examples:

  • The Finkelstein reaction is a nucleophilic substitution performed in acetone
  • Meerwein methylation can be considered a nucleophilic substitution and is typically performed in dry dichloromethane
  • Mitsunobu reactions are nucleophilic substitutions and also typically performed in the absence of water in dry organic solvents
  • The Michaelis-Arbuzov reaction is a double nucleophilic substitution typically performed in triethyl phosphite. Whether its second step is actually a nucleophilic substitution (giving bromoethane) or an elimination (giving ethene and hydrogen bromide) doesn’t even matter.

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