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Carboxylic Acid Derivatives

By James Ashenhurst

Thionyl Chloride (SOCl2)

Last updated: May 22nd, 2023 |

Thionyl Chloride, SOCl2 – Reaction With Carboxylic Acids to Give Acid Halides

  • Thionyl chloride (SOCl2) is a useful reagent for converting carboxylic acids to acid chlorides.
  • Can also  be used to convert alcohols to alkyl halides, covered in this post (See article: SOCl2 and PBr3  – also good to be aware of the SNi mechanism – SOCl2 and the SNi Mechanism)
  • Acid halides can be converted into a great number of other functional groups (esters, amides, anhydrides, and also aldehydes and ketones) through nucleophilic acyl substitution, so this reagent is extremely useful in synthesis.
  • Other reagents that perform the same transformation are PCl3, PCl5, oxalyl chloride, and the related bromine reagents.

summary of reactions of thionyl chloride reactions and mechanism

Table of Contents

    1. Thionyl Chloride (SOCl2) – Lewis structure
    2. Conversion of carboxylic acids to acid halides
    3. Conversion of carboxylic acids to acid halides by SOCl2 – mechanism
    4. Acid Halides In Synthesis
    5. Applications – Some Synthesis Problems
    6. Summary
    7. Notes
    8. Quiz Yourself!
    9. (Advanced) References and Further Reading

1. Lewis Structure of Thionyl Chloride (SOCl2)

Thionyl chloride (SOCl2) is a useful reagent for converting alcohols to alkyl halides and for converting carboxylic acids to acid chlorides. We’ve met it previously in the chapter on alcohols. (See article – SOCl2 and PBr3)

Click to Flip

SOCl2 has a sickly-sweet odor to it, like rotten eggs that have been doused in sweetener: once experienced, never forgotten. If you’ve ever had the (non-)pleasure of walking next to a pulp and paper mill, it’s very similar to the smell of sulfur dioxide.

The geometry of thionyl chloride is interesting. There are actually ten (10) valence electrons on thionyl chloride, and it adopts a geometry where one of the lone pairs occupies an orbital. With three attached atoms and one lone pair, this results in a tetrahedral arrangement of orbitals and a trigonal pyramidal molecular geometry (similar to NH3).

In this article we’ll mainly be discussing thionyl chloride’s use in converting carboxylic acids to acid chlorides, a property it shares with several other reagents such as phosphorus trichloride (PCl3), phosphorus pentachloride (PCl5), and oxalyl chloride.

We’ll also show some applications of thionyl chloride in synthesis problems.

(Thionyl chloride (SOCl2) is sometimes confused with sulfuryl chloride (SO2Cl2); sulfuryl chloride performs many of the same reactions as elemental chlorine (Cl2) while being more convenient to handle.)

2. Conversion Of Carboxylic Acids To Acid Chlorides

Thionyl chloride converts carboxylic acids into acid chlorides (“acyl chlorides”). Here is a general example, along with some specific examples.

key reaction of thionyl chloride socl2 is conversion of carboxylic acids to acid halides

The reaction also works with the related reagents PCl3, PCl5, and oxalyl chloride, which are considered to be equivalent for our purposes.

key reactions of pcl5 and pcl3 to convert carboxylic acids to acid halides

This is a useful reaction since it converts the poor leaving group HO(-) into the good leaving group Cl(-), which makes the carbonyl group much more likely to undergo nucleophilic acyl substitution reactions.   (See post: Nucleophilic Acyl Substitution Under Basic Conditions)

For specific applications, see section 4 below.

So how does it work?

3. Carboxylic Acids To Acid Chlorides With SOCl2 – The Mechanism

Thionyl chloride reacts with carboxylic acids to give an acid halide, sulfur dioxide (SO2) and HCl.

The initial reaction is between the carboxylic acid (as a nucleophile) attacking the (electrophilic) sulfur atom, resulting in replacement of H with SO2Cl. [Note 1 – this is called a “chlorosulfite ester”]

A key point of the first step is to show the carbonyl oxygen acting as the nucleophile! (Why not the OH? See  Quiz 1  )

The loss of chlorine from sulfur can be shown in two different ways.

  • One way to show this reaction happening is through an addition-elimination reaction at sulfur, except that the S-O (pi) bond breaks (addition) and then re-forms (elimination), driving off Cl(-) as the leaving group. [Note 2 – not much double bond character in S-O (pi).]

To see this mechanism, hover here or click this link.

  • Another way to show it (below) is a direct displacement at sulfur, which is tetrahedral, after all. In this sense we can think of this reaction as being a lot like an SN2 reaction at sulfur.

mechanism for conversion of carboxylic acids to acid halides - first step is direct displacement of chloride from sulfur

Once the chlorosulfite ester is formed, the acid chloride is formed through a classic addition-elimination mechanism.

  • the chloride ion then attacks the carbonyl carbon, leading to formation of C-Cl, breakage of C-O (pi).
  • The C-O pi bond is re-formed, and the C-O bond is broken.

The resulting (protonated) acid chloride is then deprotonated by Cl(-) to give the acid chloride.

mechanism for conversion of carboxylic acids to acid halides with socl2 - addition-elimination reaction

Meanwhile, the (-)O-SOCl decomposes to give foul-smelling sulfur dioxide (SO2) which bubbles off as a gas, rendering the reaction irreversible. (Reactions involving thionyl chloride should always be performed in well-ventilated fume hood – Note 3).

4. Acid Halides In Synthesis

All right. So carboxylic acids can be converted into acid halides. Now what?

Well, it opens up a whole new set of possibilities. Acyl halides undergo nucleophilic acyl substitution much more readily than carboxylic acids.

If carboxylic acids are treated with amines, alkoxides, or carboxylates (among others) the only product that will form is a deprotonated carboxylic acid (carboxylate).

nucleophilic acyl substitution of carboxylic acids fails basic conditions

As discussed earlier, that’s because under basic conditions, the leaving group of a carboxylic acid is not the hydroxide ion (HO-) but the di-anionic (and extremely basic) O(2-).

Carboxylic acids undergo nucleophilic acyl substitution under acidic conditions, but that’s a different story. (See Carbonyl Mechanisms – Elimination)

Once the carboxylic acid is converted into an acid halide, however, a large number of nucleophilic acyl substitution reactions become possible.

key reactions of acid halides - summary map - esters amides anhydrides aldehydes ketones

 

 

5. Applications – Synthesis Problems

Once this reaction is in your synthetic toolbox, it opens up solutions to a wide range of solutions to synthesis problems.

See if you can come up with two-step pathways to synthesize each of the three molecules below.

Click to Flip

The way in which SOCl2 enables conversion of carboxylic acids to much more versatile acid halides is extremely similar to how SOCl2 allows conversion of alcohols to alkyl halides, which can subsequently be converted into a huge range of different products via SN1/SN2/E1/E2 reactions (See, for example, The Power of the SN2 Reaction)

conversion of alcohols to alkyl halides

6. Summary

  • Thionyl chloride can convert carboxylic acids to acid halides.
  • The acid halides can then be converted into aldehydes, ketones, anhydrides, esters, amides or a number of other functional groups. (Including back to a carboxylic acid – just add water! )
  • In this way, carboxylic acids can be converted (in about 2 steps) into a large variety of different carbonyl compounds.
  • You must know this reaction (or others like it, i.e. PCl3, PCl5, oxalyl chloride) if you are going to successfully plan out syntheses of carboxylic acid derivatives.

Notes

Related Articles

Note 1. This has the effect of replacing the OH with the good leaving group (-)OSOCl, which is the conjugate base of the (unstable) molecule chlorosulfinic acid. As soon as (-)OSOCl is displaced, it almost immediately breaks down to sulfur dioxide (SO2) gas and chloride ion.

Note 2. It’s very tempting to think of the S=O bond as behaving a lot like the C=O bond and undergoing similar reaction pathways like addition-elimination.

The correlation between C=O and S=O isn’t that great however. As noted previously, the sulfur atom is tetrahedral, not trigonal planar; the energetic “penalty” for losing a leaving group on an sp2 hybridized atom is considerably less for the heavier, more polarizable sulfur than it is for carbon. Furthermore it the S-O “pi bond” does not have very much double bond character.  It is often written as S(+)-O(-) to reflect the highly polar nature of this bond.

So although you may see this mechanism written, it is an open question as to how well it corresponds to reality.

Note 3. One accident that occurred during my time as a TA involved a student dropping a flask with 5 mL of thionyl chloride into a rotovap bath outside the fume hood. The cloud of SO2 and HCl that formed cleared the teaching lab for half an hour, so you can imagine what thionyl chloride would do if exposed to the moisture in your lungs. Treat with caution, just as you would if you were working with phosgene.

Quiz Yourself!

Click to Flip

 

(Advanced) References and Further Reading

  1. Phthalyl Chloride
     P. Kyrides
    Journal of the American Chemical Society 1937, 59 (1), 206-208
    DOI:     10.1021/ja01280a051
    An early paper on the conversion of phthalic anhydride to the diacid with SOCl2, as well as the reverse reaction, which can regenerate SOCl2.
  2. Structure of Succinyl Dichloride and of Certain Other Potentially Cyclic Difunctional Compounds
    JAMES CASON and ELMER J. REIST
    The Journal of Organic Chemistry 1958, 23 (10), 1492-1496
    DOI:10.1021/jo01104a024
    In this paper, succinyl dichloride is only obtained from the acid with an excess of SOCl2 and a catalytic amount of pyridine. Pyridine can be used to catalyze the reaction of SOCl2 with carboxylic acids.
  3. Eine Methode zur katalysierten Herstellung von Carbonsäure‐ und Sulfosäure‐chloriden mit Thionylchlorid
    H. Bosshard R. Mory M. Schmid Hch. Zollinger
    Helv. Chim. Acta 1959, 42 (5), 1653-1658
    DOI: 10.1002/hlca.19590420526
    This paper discusses how DMF (N,N-dimethylformamide, a common solvent) can be used to catalyze the reaction of SOCl2 with carboxylic acids, which is commonly used today.
  4. n-BUTYRYL CHLORIDE
    Helferich and W. Schaefer
    Org. Synth. 1929, 9, 32
    DOI: 10.15227/orgsyn.009.0032
    A classic procedure for the conversion of carboxylic acids to acid chloride with SOCl2 from Organic Syntheses, a reliable source of independently tested organic transformations.
00 General Chemistry Review
01 Bonding, Structure, and Resonance
02 Acid Base Reactions
03 Alkanes and Nomenclature
04 Conformations and Cycloalkanes
05 A Primer On Organic Reactions
06 Free Radical Reactions
07 Stereochemistry and Chirality
08 Substitution Reactions
09 Elimination Reactions
10 Rearrangements
11 SN1/SN2/E1/E2 Decision
12 Alkene Reactions
13 Alkyne Reactions
14 Alcohols, Epoxides and Ethers
15 Organometallics
16 Spectroscopy
17 Dienes and MO Theory
18 Aromaticity
19 Reactions of Aromatic Molecules
20 Aldehydes and Ketones
21 Carboxylic Acid Derivatives
22 Enols and Enolates
23 Amines
24 Carbohydrates
25 Fun and Miscellaneous
26 Organic Chemistry Tips and Tricks
27 Case Studies of Successful O-Chem Students

Comments

Comment section

63 thoughts on “Thionyl Chloride (SOCl2)”

  1. Hi
    I have an equestion please
    Which is more reactive carboxyl group or hydroxyl group toward thionylchloride (these to functional groups are meta position to each other in certain compound )?I try to synthesis acyl chloride derivarive on carboxyl group , Is that possible in this case ?

    Reply

    1. If it is a phenol, it will be unreactive towards thionyl chloride since SN2 type reactions are impossible. The acyl halide will be formed instead, however I strongly suggest protecting your phenol group, otherwise you will end up with a mess.

      Reply

  2. This was done awhile ago. I would recommend protonation deprotonation as two separate steps now. Past introductory organic chemistry, we often just say “proton transfer” and be done with it, like waving a magic wand.

    Reply

  3. Chloride ion can be an OK base. It’s competent to to the deprotonation to restore aromaticity in electrophilic aromatic substitution reactions. Some counterions aren’t basic enough to do this (e.g. triflate).

    Reply

  4. By the way your table of 9 or 10 carbonyl mechanism is absolutely fantastic. It was a great idea to have this PT step instead of a protonation-deprotonation.
    But aren’t some teacher going to complain about this internal reaction?

    Reply

  5. Last step:
    I have never seen a Cl- deprotonate anything. Maybe we should have H20 do it.

    Reply

  7. What about if you have both an alcohol and carboxylic acid in the molecule and both are chlorinated? With an imidazole present, is it acting as a base to deprotonate the carboxylic hydroxyl or is it acting as a solvent?

    Reply

  8. “The HOSCl breaks down into HCl and sulfur dioxide gas, which bubbles away.”

    I believe you intended to write HOSOCl

    Reply

  9. Could you please comment on the possible reaction of phenols and SOCL2 ? Is there any chance that they undergo similar transformations like alcohols?

    Reply

  10. The reaction of methanol with thionyl chloride and tetrahydrofuran results in the opening of opening of the furan ring.
    A very useful reaction.
    Read the useful obeservations and comments.

    Reply

  11. Is it possible to have a selective chlorination with SO2Cl when in the molecule there are both carboxylic acid and alcool?

    Reply

  12. Hi my question is that when I add socl2 to benzyl alcohol and then I further add alcl3 which compound do I get? Wasn’t able to solve it

    Reply

    1. I think you would get a mess, to be honest. SOCl2 to benzyl alcohol would conceivably get you benzyl chloride, but once you add AlCl3, it’s going to be a messy polymerization.

      Reply

  14. Which bond breaks first in reaction of an isolated chlorosulphite with 1-phenylmethanol?which(C-O or S-Cl) bond break first in mechanism,because both bond break simultaneously,and it is still not certain is written in book.

    Reply

    1. It is unclear from your question exactly what reaction you are referring to. It’s possible that the S-Cl bond breaks first, giving an ion pair, and then Cl- attacks carbon. That would be my guess.

      Reply

  15. James,

    In your “formation of acid chlorides” mechanism, I noticed that in the principal step with the concerted elimination you showed the chloride departing from the sulfoxide directly, rather than via a tetrahedral intermediate in addition-elimination style. My understanding is that when the carbon variety of acyl halide undergoes nucleophilic addition, the pi bond first breaks and localizes to the oxygen before a lone pair there reforms the carbonyl and kicks out the halide in a beta-elimination via lone pair mechanistic step. I understand this happens rather than the halide departing in a concerted fashion when the carbonyl is attacked (i.e., an “SN2”-style mechanism), because the carbonyl pi-bond is weaker than the C-X sigma bond. So, my question is: is your depiction of an “SN2-style” attack on the sulfur accurate or just for convenience? I believe sulfur can undergo SN2-like substitutions via a pentavalent intermediate (as opposed to transition state), but I’m not sure if that would really apply here.

    Thanks,

    Rich

    Reply

  16. Hi…
    I have a question can we prepare amide from amino acid and an amine by thionyl chloride without any protection of amine group of aminoacid?
    Thanks

    Reply

  17. Actually this blog is really helpful. But I still confuse about how to control the reaction if there are several functional groups are present in the molecule such as alcohol and carboxcylic acid, and I wanna produce an amide product ? How to avoid thyonil chloride attacks the alcohol ? So it prefer to the carbocylic acid ?
    Thanks a lot.
    I’m still doing my thesis.

    Reply

  18. That s a really wonderful website! Makes thing much much clearer than with my quite obscure class….
    Thank you so much.

    Reply

  19. Hi
    congratulations for the blog it’s very well wrote and good.
    I have a question, if a molecule have an ester and a carboxylic acid on it’s structure, what do you thing the thionyl chloride will prefer to attack or will attack both?

    Reply

    2. This is a tricky reaction dear… This is what happens…
      # Thionyl chloride first attacks the carboxylic group. Produces HCl and SO2…
      # If you are heating the contents at above 70-80 degrees Celsius, then the HCl produced will attack the Ester, and breaks into -COOH and –OH…
      # The SOCl2 present would react with the formed alcohol too…
      # This is why you must add base like triethyl amine (my choice) or Pyridine to consume the HCl…

      All the best… There is still more explanation… But, I hope you got an idea, what actually happens in the system…

      Reply

  22. Does anyone have an experimental procedure for actually performing a chlorination of an alcohol with inversion of configuration? I’ve found lots of slides and lectures notes on the theory behind the mechanism, but nothing stepwise showing how it was really performed in a lab and what yields were achieved in the product.

    I recently tried this experiment with a trans-4-t-butylcyclohexanol/pyridine and SOCl2 and seemed to fail quite miserably.

    Reply

  23. Nice Job here.
    I do have a question. How does the a reaction proceed when there is both an alcohol and an ester present? Esterification of Amino Acids in the presence of thionyl chloride and methanol for example. I assume it is a competing reaction, but the thing that confuses me is ester product is favored, while the alcohol seems to be more reactive.
    Any comments would be appreciated, Thanks.

    Reply

  24. In my observation, I believe that synthesizing compound is one part, and separating the product and purifying and recrystallizing is the major part :)

    Reply

  25. I really wonder if SOCl2 could produce a dense fumes or cloud of SO2 or HCl when spilled into water… I mean, you can recreate it once again. Although in my observation, it is possible only if amines (any amines or ammonia) content is present. Then the fumes (white cloudy) is hard to expel, because they settle down and exhausting them will be difficult.

    Reply

  26. Dear Dr James,

    HI Dr. Nice to meet you. I am a PhD student from Malaysia. I have some problems regarding the reaction between carboxylic acid and thionyl chloride. I would like to react graphene oxide with thionyl chloride in order to change the COOH functional group on the surface of graphene oxide to COCl. May I know the what is the reaction conditions? How much temperature the reaction should be carry out and what is the amount ratio that thionyl chloride should be used?

    Reply

  27. sir as a viewer has asked about this rxn in presence of pyridine pls show it also as it may enhance understanding.according to me pyridine would accept h+ from hcl and give cl- and normally the product has retention of configuration and using pyridine may give excess cl- will give inversion product

    Reply

  28. i want to ask you sir .in mechanism of formation of chloroalkane with socl2 why sulphur is attracting electrons of oxygen yet oxygen is more electronegative?
    please reply.

    Reply

  29. You said that SOCl2 is sovent dependent. So please tell me What happens when SOCl2 reacts with (S)-2-butanol in presence of ether and also what happens when solvent is pyridine?
    The far I can guess that Both the solvents are polar aprotic and the reaction will go for Sn2 mechanism. So Tell me where will retention and where will inversion will occur. And also the products’ name from the reaction.

    Reply

  30. hi
    i want to buy of you 2mt thionyl chloride first to check the quality and your ability on shipping it to tehran
    then after it i will buy 20mt
    yours trully

    Reply

  31. I am sorry but who taught you that mechanism? Alcohols and SOCl2 always react with retention and it’s an ipso-substitution, not SN2, there is no backside attack and no pentavalent transition-state. If you want an inversion, you need a catalytic nucleophile (e.g. lewis-base or heteroatom-solvent) which basically is cheating the mechanism because the nucleophile inverts the stereocenter, not the chloride, which itself inverts the new stereocenter. The mechanism as drawn above is wrong. It’s not a white lie, it’s just a wrong mechanism. SOCl2 is specifically used for retention!

    Reply

  32. Hi,

    I learnt in school that Alcohols, alkyl flourides, ethers and amines do not typically undergo sn2 reactions. But why is this alcohol undergoing a sn2 reaction? the transition state is not a tosylate or mesylate right? I don’t understand this. Can you please explain! thanks a lot! :)

    Reply

    1. Well, the coordination of oxygen to the sulfur makes the oxygen a good leaving group (much like a tosylate or mesylate); hence the chloride ion can then displace it in an SN2 reaction!

      Reply

  33. I dont know. but the secont step is acylation of fridle-crafts and in this step i dont have produt. that is,probably i dont have acyl halide in the first step.

    Reply

    1. Don’t take the acid chloride out. It reverts back to acid once it’s of the container. Why don’t you try dissolving both your reagents in solvents like DCM or CHCl3 and add thionyl chloride drop wise?

      Reply

  34. HI
    I am going to do a acylation reaction of acid with thionyl chloride in persent of methylene chloride (solvent) and DMF(catalyst) at room temperature.i don’t have experience to this reaction.
    according to TLC method, Progress of the reaction is low.
    The raw material(acid) is a HCl salt in N atom.
    Please guide me
    thank you and best regards

    Reply

  35. There are two mechanisms to this reaction. In general, treatment of a chiral secondary alcohol to thionyl chloride gives predominantly RETENTION of stereochemistry and NOT inversion…..

    Reply

  36. One might add that thionyl chloride is not flat, as it is commonly depicted, but pyramidal, just like amines with one lone pair sticking out. (Sulfoxides substituted with two different groups are therefore chiral. The inversion barrier is often high enough to make the separation of sulfoxide enantiomers possilble.)

    If you think thionyl chloride is bad, which it indeed is, you should also know it has an evil twin: Sulfuryl chloride (SO2Cl2). That is one unhappy liquid.

    Reply

    1. I have thankfully avoided working with SO2Cl2, but that doesn’t mean I haven’t experienced it from fume hood neighbors. Nasty stuff!

      Reply

  37. Make some extra space for the 3rd structure in the 4th reaction scheme (Formation of alkyl chlorides), so that the chlorine on the right is shown properly. But otherwise, great work, as usual. Maybe a few words about alternative reagents for this transformation would be useful, too.

    Reply

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