Today, in my organic chemistry class, I learnt about the nucleophilic substitution reaction. The notes have stated that:

Alkyl halides with $\alpha$ oxygen atom can also undergo SN1 reaction because of the heteroatom stabilised cation (oxonium ion)

An example was then given of a bromide leaving from a bromoether to give a resonance-stabilised carbocation.

I was wondering if alkyl halides with an $\alpha$ nitrogen atom can undergo SN1 reaction as well. When asked, the teacher responded by saying that with $\alpha$ nitrogen atoms, the carbocation would experience greater stabilisation and result in a faster rate of SN1 reaction for such alkyl halides.

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  • $\begingroup$ Ask yourself if nitrogen can sustain a positive charge better than oxygen. $\endgroup$ – user55119 Apr 16 '18 at 15:39

The reactivity of haloalkyl ethers are well documented (e.g., they were originally used to protect $\ce{-OH}$ groups during total syntheses). For instance, chloromethyl methyl ether had been used to protect alcohol and phenol $\ce{-OH}$s as $\ce{-OCH2OCH3}$ or commonly known as $\ce{-OMOM}$. They should be sealed and stored in freezer to protect from moisture because they are susceptible to decompose by reacting with water, showing their reactivity. They are also well known carcinogens. An early review on $\alpha$-haloalkyl ethers can be found in Chemical Reviews (1955)([Ref. 1]).

A recent example in Ref. 2 shows in situ preparation of $\alpha$-halo ethers to protect $\ce{R-OH}$ groups, in order to prevent researchers from exposure to carcinogenic $\alpha$-halo ethers (see Figure below):


For example for carcinogenic activity of a $\alpha$-halo ether: Human health assessment information on bis(chloromethyl)ether can be found on the IRIS website (https://www.epa.gov/iris). IRIS stands for Integrated Risk Information System, a part of EPA’s mission to protect human health and the environment.

Based on the high reactivity of $\alpha$-halo ethers, one can expect $\alpha$-halo amine would have been even higher reactivity than them. To my knowledge, they do not exist, mainly because, they'd undergo elimination quickly to give relevant Schiff bases (see below): $$\ce{-> [R-CH(Cl)-NHR1] -> R-CH=NR1 + HCl} \ \mathrm {or}$$ $$\ce{-> [R-CH(Cl)-NR1R2] -> R-CH=N+R1R2Cl-}$$

[Ref. 1]: The alpha-Haloalkyl Ethers: Lawrence Summers, Chem. Rev., 1955, 55(2), 301-353 (DOI: 10.1021/cr50002a003).

[Ref. 2]: Simple, Rapid Procedure for the Synthesis of Chloromethyl Methyl Ether and Other Chloro Alkyl Ethers: M. A. Berliner, and K. Belecki, J. Org. Chem., 2005, 70(23), 9618-9621 (DOI: 10.1021/jo051344g).


Recently, I have found some literature which does help to answer my question.

On p. 339, Clayden, Greeves, & Warren (2012) did mention that in general, $\alpha$- nitrogen, as well as sulfur, substituents can effectively provide resonance stabilisation to the carbocation, facilitating the $\ce {S_N1}$ process.

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Similarly, on p. 433, Carey & Sundberg (2007) mentioned :

Adjacent atoms with one or more unshared pairs of electrons strongly stabilize a carbocation. Table 3.11 (p. 304) indicates the stabilization of the methyl cation by such substituents. Alkoxy and dialkylamino groups are important examples of this effect.

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More interesting information

When we see such circumstances of resonance stabilisation, I believe many of us may question to what extent is this effect at play because this seemingly goes against conventional understanding as more electronegative atoms are bearing the positive charge. To this, Carey & Sundberg (2007) went on to say:

Although these structures have a positive charge on a more electronegative atom, they benefit from an additional bond that satisfies the octet requirement of the tricoordinate carbon. These “carbocations” are best represented by the doubly bonded resonance structures. One indication of the strong participation of adjacent oxygen substituents is the existence of a barrier to rotation about the C−O bonds in this type of carbocation.

If you think about it, it does make perfect sense since you are making an extra bond through this resonance effect. The exothermicity of bond formation more than compensates for the placement of the positive charge on the electronegative atom.


Carey, F. A., & Sundberg, R. J. (2007). Advanced Organic Chemistry Part A. Structure and Mechanisms (5th ed.). Springer.

Clayden, J., Greeves, N., & Warren, S. (2012). Organic Chemistry (2nd ed.). New York : Oxford University Press Inc.


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