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A bit of a follow-up to Why is thionyl chloride preferred for preparing alkyl chlorides from alcohols?.

The reaction with $\ce{SOCl2}$ is also used instead of $\ce{PCl3}$ and $\ce{PCl5}$ when retention of stereochemistry is required. Phosphorus trichloride and phosphorus pentachloride both lead to inversion.

SNi mechanism with thionyl chloride. (Chemsketch)

The mechanism proceeds via a $\mathrm{SN_i}$ pathway, or internal nucleophilic substitution. This step has been highlighed in red; an intimate ion pair$^{[\text{see below}]}$ is given in square brackets. Adding a nucleophilic solvent such as pyridine considerably increases inversion with $\ce{SOCl2}$ via an attack at the sulfur atom. Green marks blocking of the intramolecular substitution; blue is for inversion.

Thionyl chloride with pyridine. No SNi. (Chemsketch)

  • As far as I know, $\ce{POCl3}$ has not been seen following an $\mathrm{SN_i}$ mechanism (even without pyridine). Why?

If possible, please provide a qualitative mechanistic reason. Something that is readily explained by waving hands. Regardless of whether such an approach is achievable, quantitative (calculational) answers are also most welcome.

References discussing intimate ion pair formation

  • F. A. Carey, R. J. Sundberg. $(2007)$. Advanced Organic Chemistry Part A: Structure and Mechanisms, $4$th edition, pp 269$-$276. ISBN: 0-306-46242-7
  • W. A. Hughes, E. D. Cowdrey, C. K. Ingold, S. Masterman, A. D. Scott. 'The Mechanism of Elimination Reactions. Part 1. Unimolecular Olefin Formation from Alkyl Halides in Bulphur Dioxide and Formic Acid'. Journal of the Chemical Society, $(1937)$, 1271$-$1277. DOI: 10.1039/JR9370001271
  • E. S. Lewis, C. E. Boozer. 'The Kinetics and Stereochemistry of the Decomposition of Secondary Alkyl Chlorosulfites'. Journal of the American Chemical Society, $(1952)$, 74, 308$-$311. DOI: 10.1021/ja01122a005
  • D. J. Cram. 'Studies in Stereochemistry. XVI. Ionic Intermediates in the Decomposition of Certain Alkyl Chlorosulfites'. Journal of the American Chemical Society, $(1953)$, 75, 332$-$338. DOI: 10.1021/ja01098a024
  • C. C. Lee, A. J. Finlayson. 'Rearrangement In The Reaction Between Thionyl Chloride And $3$-Methyl-$2$-Butanol. Canadian Journal of Chemistry, $(1961)$, 39(1): 260$-$261. DOI: 10.1139/v61-030
  • C. C. Lee, J. W. Clayton, D. G. Lee, A. J. Finlayson. 'Rearrangement Studies With $\ce{^14C-XIII}$: The Thermal Decomposition Of $1$-$\ce{^14C}$-$2$-Butyl Chlorosulfite'. Tetrahedron, $(1962)$, 18 1395$-$1402. DOI: 10.1021/ja01098a024
  • H. Patin, G. Mignani, C. Mahe, J-Y. Le Marouille, A. Benoit, D. Grandjean. 'Ferrocenyltrithiocarbonates: I. Direct access from α-ferrocenylcarbinols by a $\mathrm{SN_i}$ mechanism. Absolute x-ray structure determination of (R)-ferrocenylmethylmethane S-methyl-trithiocarbonate'. Journal of Organometallic Chemistry, $(1980)$, 193, 1, 93$-$103. DOI: 10.1016/S0022-328X(00)86079-9
  • J. L. Kice, G. C. Hanson. 'Mechanisms of SNi reactions. Effect of aralkyl group structure on ion-pair return in the decomposition of aralkyl thiocarbonates'. Journal of the American Chemical Society, $(1973)$, 38 (7), 1410$-$1415. DOI: 10.1021/jo00947a037
  • M. B. Smith. $(2013)$. March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, $7$th edition, pp 311, 486$-$487, 490, 598, 1316. ISBN: 978-0-470-46259-1
  • The $\mathrm{SN_i}$ (substitution nucleophilic internal) mechanism: retention of configuration. Powerpoint presentation, Università degli Studi di Napoli Federico II.
  • James. $\ce{SOCl2}$ and the $\mathrm{SN_i}$ Mechanism. Master Organic Chemistry, Alcohols. webpage
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  • $\begingroup$ Hopefully, the subscript letter $\mathrm{i}$ in $\mathrm{SN_i}$ is clearly visible, and so is not to be confused with $\mathrm{SN_1}$. (I for one initially thought it was a typo when I learned about it in December.) $\endgroup$
    – Linear Christmas
    Feb 22, 2017 at 16:12
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    $\begingroup$ I don’t like the mechanisms as drawn due to the $\ce{S=O}$ double bonds which should be $\ce{\overset{+}{S}-\overset{-}{O}}$, but still $+1$ for a good question. $\endgroup$
    – Jan
    Feb 22, 2017 at 23:29
  • $\begingroup$ @Jan I'll see what I can do about it after school tomorrow ;) $\endgroup$
    – Linear Christmas
    Feb 22, 2017 at 23:34
  • $\begingroup$ @Jan I have updated the mechanism to include more delocalisation and true ionic bond character (both with dashed lines). Sadly, this has made the mechanism a bit harder to follow but is still alright. If there's anything amiss, feel free to ping me. $\endgroup$
    – Linear Christmas
    Feb 23, 2017 at 16:39
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    $\begingroup$ How is the reaction using thionyl chloride providing the product from retention? The chloride is attacking the activated alcohol from the back side, correct? Whether it's intramolecular or intermolecular is irrelevant. $\endgroup$
    – jerepierre
    Feb 23, 2017 at 19:04

2 Answers 2

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The step in the red box is wrong. You probably get dissociation to form an ion pair. The pair quickly collapses, leading to chloride attack on the cation before any dissociation or diffusion occurs so that you get the retention of stereochemistry.

For phosphorus based chlorination, this ion-pair mechanism is probably not favorable, though it's not clear to me why this is the way it is.

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  • $\begingroup$ Actually in the process of editing that step (or considering at least). A ton of references will be added in a second. (There are also places where the ion pair is said to be 'not completely dissociated', and where it is not included.) $\endgroup$
    – Linear Christmas
    Feb 23, 2017 at 21:51
  • $\begingroup$ Zhe is right. It is a common misconception to write this mechanism as a direct displacement which is actually impossible on stereoelectronic terms. $\endgroup$
    – EJC
    Feb 23, 2017 at 22:30
  • $\begingroup$ There's just no way for the intramolecular $\mathrm{S}_{N}2$ reaction as written to take place, from a stereoelectronic perspective. There's probably some give on how tight the ion pair has to be though it has to be tight enough to explain retention. But we're in a gray area where mechanistic probes are probably going to be quite difficult. $\endgroup$
    – Zhe
    Feb 23, 2017 at 22:52
  • $\begingroup$ @Zhe Yeah, the final sentence hits the nail on the head. ---- If the chlorine in the red box attached to sulfur has significant ionic character, wouldn't that make the "one-step" method (that I currently have) more probable? (as a last resort, I'm a bit too lazy to rewrite the mechanism again at the moment :D) $\endgroup$
    – Linear Christmas
    Feb 23, 2017 at 23:05
  • $\begingroup$ It's still probably not one-step. The proposed transition state for a front side $\mathrm{S}_{N}2$ reaction seems unlikely. Therefore, I would think that we have (at least) two steps though the barriers would be quite small... $\endgroup$
    – Zhe
    Feb 24, 2017 at 17:00
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Once the alcohol attacks the SOCl2 the proton on the oxygen is more acidic because S is more electronegative than P.

What is likely happening is that R-OH-SOCl has a lower pKa than 5.2 (the pKa of the conjugate acid of pyridine), giving the chlorine time to do a nucleophilic attack.

Then R-OH-POCl2 should a pKa close enough to 5.2 that the equilibrium results in a low enough concentration of deprotonated R-O-POCl2 that the Cl- cannot find any. Since the elimination reaction is practically irreversible all of the R-OH-SOCl will be consumed well before the Cl- has a chance to find anything to react with .

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