[ecnerwalc3321]

I have molecule with a carboxylic acid end (pyrene butyric acid).  I was thinking about changing the acid end to a triple bond in order to do click chemistry (azide-alkyne reaction).  I was thinking about treating the acid (solid) with excess SOCl2 at room temperature (?) and waiting until all the HCl and SO2 evolution stops.  After some time, propargyl alcohol will be added dropwise into reaction chamber.  theoretically, the acid chloride will just react with the alcohol and my end product will be formed along with more HCl.    However, I was worried that the HCl formed in this process will react with the triple bond and thus render my product less pure.  Does anyone have experience with HCl reactions with alkynes?  Does the reaction occur readily at room temperature and do you see any shortcomings with my overall synthesis?  Thanks.

 (Not a chemist by trade-finding out that theory and practice is quite different).

[discodermolide]

I have molecule with a carboxylic acid end (pyrene butyric acid).  I was thinking about changing the acid end to a triple bond in order to do click chemistry (azide-alkyne reaction).  I was thinking about treating the acid (solid) with excess SOCl2 at room temperature (?) and waiting until all the HCl and SO2 evolution stops.  After some time, propargyl alcohol will be added dropwise into reaction chamber.  theoretically, the acid chloride will just react with the alcohol and my end product will be formed along with more HCl.    However, I was worried that the HCl formed in this process will react with the triple bond and thus render my product less pure.  Does anyone have experience with HCl reactions with alkynes?  Does the reaction occur readily at room temperature and do you see any shortcomings with my overall synthesis?  Thanks.

 (Not a chemist by trade-finding out that theory and practice is quite different).

A couple of options:
If you are worried by this azeotrope the acid chloride with toluene several times, this should remove any HCl left.
Your acid chloride may well be a solid, in which case you can crystallise it.

[james_a]

If you use a slight excess of pyridine w/ socl2, you'll mop up any excess HCl.

[ecnerwalc3321]

@discodermolide,

I would think that my acid chloride would be a solid.  However, when I tried carrying out the reaction (~70C, reflux, 2 hours, then distill SOCl2), I'm left with an oily substance.  The "oil' doesn't go away even when I vacuum dry it.  The butyric acid does dissolve in SOCl2 and chloroform, however.

How would I wash it in toluene if the acid chloride reacts with water?  I suppose I could use two organic layers in a sep funnel?

@james_a

So use pyridine as a solvent and run the reaction.  After the reaction, do you think I need to distill the pyridine before adding the propargyl alcohol?  Or can it be a one-pot synthesis?

[discodermolide]

@discodermolide,

I would think that my acid chloride would be a solid.  However, when I tried carrying out the reaction (~70C, reflux, 2 hours, then distill SOCl2), I'm left with an oily substance.  The "oil' doesn't go away even when I vacuum dry it.  The butyric acid does dissolve in SOCl2 and chloroform, however.

How would I wash it in toluene if the acid chloride reacts with water?  I suppose I could use two organic layers in a sep funnel?

@james_a

So use pyridine as a solvent and run the reaction.  After the reaction, do you think I need to distill the pyridine before adding the propargyl alcohol?  Or can it be a one-pot synthesis?

You misunderstood me, sorry.
I make acid chlorides made by dissolving the acid in SOCl2. But you can use toluene as a solvent. Don't put it near water. When the reaction is complete just remove the toluene, add more toluene and re-evaporate. Repeat two or three times, then it should be good to use, and may even crystallise.

[ecnerwalc3321]

May I ask how you make your acid chlorides?  What do "mild" conditions typically entail?  Can you just simply dissolve your acid in SOCl2 at room temperature and let the excess SOCl2 evaporate?  I've been refluxing mine in a heated water bath and I'm not sure whether this has a big influence on the product (the water is outside the glass, right?).  So far, the several IR spectra has been inconclusive due to "oily" product formed.

[discodermolide]

May I ask how you make your acid chlorides?  What do "mild" conditions typically entail?  Can you just simply dissolve your acid in SOCl2 at room temperature and let the excess SOCl2 evaporate?  I've been refluxing mine in a heated water bath and I'm not sure whether this has a big influence on the product (the water is outside the glass, right?).  So far, the several IR spectra has been inconclusive due to "oily" product formed.

Dissolve or suspend in SOCl₂, or toluene, then add SOCl₂ heat if required. Monitor by TLC after quench with methanol. Evaporate solvent, then co-evaporate with toluene two or three times to remove volatile material (assuming acid chloride is not volatile). Then use it directly.
Note everything should be dry.

[orgopete]

Isn't the acid chloride pyrenebutyric acid a known compound? You could look up how it was made.

By the way, my preferred way to make an acid chloride is to use dilute my compound in an inert solvent, add thionyl or oxalyl chloride and add a catalytic amount of DMF. DMF becomes converted to an iminoyl chloride which makes the acid chloride and regenerates DMF. The procedure can be found in Fieser and Fieser (if that is still used?).

[discodermolide]

Isn't the acid chloride pyrenebutyric acid a known compound? You could look up how it was made.

By the way, my preferred way to make an acid chloride is to use dilute my compound in an inert solvent, add thionyl or oxalyl chloride and add a catalytic amount of DMF. DMF becomes converted to an iminoyl chloride which makes the acid chloride and regenerates DMF. The procedure can be found in Fieser and Fieser (if that is still used?).

My method is a hangover from chemical development. The iminoyl chlorides are unstable and can cause problems on scale with very exothermic decomposition taking place. This is why I don't generally recommend it.

[orgopete]

I'm not surprised if you added DMF to similar mixtures. This sounds like a hang-fire mixture. I did my reactions in the inverse. I added the thionyl chloride or oxalyl chloride. If it didn't start percolating, I would add a little more DMF. I was discovery, so I generally didn't have lethal generations of heat and gas.

[g-bones]

I am pretty confident you will be fine.  If I recall correctly, it takes some force to react an alkyne with HCl (large amounts of HCl and high temperatures).  If your worried about it, you could always use alternative esterification conditions like create an anhydride from your carboxylic acid then react it with your alcohol.  I would say give you reaction a go and see what happens.  Thats typically how I find out if things will tolerate reaction conditions    Only on material that is moderately easy to come by of course 

[orgopete]

I am pretty confident you will be fine. …

I agree. I think the main problem has been the preparation of the acid chloride. I have made esters from propargyl alcohol with an acid chloride. This reaction can be carried out without addition to the triple bond.

[ecnerwalc3321]

Thanks for all the suggestions.  I tried all your suggestions along with some different variations in separation, reaction, etc but seem to always come up with the same result as far as what the IR spectra shows.  The spectra on top is the pure acid chloride while the one on the bottom is the "acid chloride derivative" which looks suspiciously like water's IR spectra.  Two things worries me; that is, the presence of what is perceived to be an alcohol peak at 3400 cm-1 and the unchanging carbonyl peak at ~1700 (should be shifted to ~1800 due to the withdrawing power of Cl). 

For this particular sample, I placed ~0.02g PBA in a vial and added 2 ml of SOCl2 along with a couple drops of DMF.  The solution was stirred at room temperature overnight in hood.  ~15 mL of hexane was then added directly to the solution to form precipitate and the solution was dried in a vacuum oven (no heat).  End product looked slightly sticky.  IR spectra was taken by forming KBr pellet. 

I suppose my question is, "why would a peak appear at 3400?"  While I was doing the experiments, I had concerns that I didn't keep the environment dry enough.  However, IF the environment still had some water, either from the air or whatever chemicals I used, wouldn't the carboxylic acid be favored?  If so, why would I get a different spectra?  Shouldn't I get the same spectra as PBA if my samples were exposed to moisture?

[discodermolide]

It's sticky probably because the HCl and SO₂ are still in there. As I said above:
Dissolve or suspend in SOCl₂, or toluene, then add SOCl₂ heat if required. Monitor by TLC after quench with methanol. Evaporate solvent, then co-evaporate with toluene two or three times to remove volatile material (assuming acid chloride is not volatile). Then use it directly.
Note everything should be dry.

HCl especially has a nasty tendency to make solids sticky, that's why several toluene evaporations help.

[ecnerwalc3321]

How would the presence of HCl and SOCl2 explain the IR peaks that I see?