[Ion.liq]

Hi everyone,
I need your help... I would like to prepare 3-(Chloromethyl)-2-hydroxybenzaldehyde.
In SciFinder I found a few recipes:

DOI   https://doi.org/10.1039/D0NJ03637D (PHOTO 1)
DOI  https://doi.org/10.1016/j.fuel.2021.121154 (PHOTO 2)

but on a scheme of reaction (PHOTO 3) is ZnCl2 as a catalyst. In any recipe, ZnCl2 was no included.
I tried with 1:1 molar ratio salicylaldehyde:ZnCl2 and formaline:ZnCl2
The obtained product was 5-(Chloromethyl)-2-hydroxybenzaldehyde or the mixture this two compounds.
Maybe you have some suggestion?

Synthesis of 5-(Chloromethyl)-2-hydroxybenzaldehyde is very simple. I mixed by 48 hours paraformaldehyde, salicylaldehyde and HCl 37% at room temperature. The yield f reaction was above 80%. But sythesis of 3-(Chloromethyl)-2-hydroxybenzaldehyde was difficult. Maybe ZnCl2 as a Lewis acid catalyst is necessary?

[rolnor]

Your reference seems good so you should not need to change anything, just follow the recipe carefully.

[Ion.liq]

Your reference seems good so you should not need to change anything, just follow the recipe carefully.

but if I followed the recipe (not included ZnCl2) I obtained 5-(Chloromethyl)-2-hydroxybenzaldehyde not 3-(Chloromethyl)-2-hydroxybenzaldehyde

[rolnor]

They have NMR-data in the reference. Its hard to think they have the wrong material. Do you follow the procedure exactly?

[kriggy]

There might be a typo since the protocols doesnt include ZnCl2 unlike the schemes right?

I think the problem lies in the fact that all papers refence a same one:

10.1016/j.tetlet.2006.09.149

which has functional group at the 5 position therefore your reaction cant go there. Maybe try it without ZnCl2 or get 5-bromo salicylaldehyde and after your synthesis hydrogenate it with Pd/C and hydrogen to get rid of the bromine

[Ion.liq]

They have NMR-data in the reference. Its hard to think they have the wrong material. Do you follow the procedure exactly?

So, tell me what is different in these two synthesis 5-(Chloromethyl)-2-hydroxybenzaldehyde and 3-(Chloromethyl)-2-hydroxybenzaldehyde (temperature?)

5-substituted - https://doi.org/10.1039/B613705A
3- substituted (post 1)

These procedures are the same for me, but they obtained two different compounds.

I prepared 5-(Chloromethyl)-2-hydroxybenzaldehyde using this same procedure, but I used paraformaldehyde, not formaldehyde, HCl, and salicylaldehyde, and NMR spectra of 5-(Chloromethyl)-2-hydroxybenzaldehyde is below

Is it possible to obtain two different compounds using formaldehyde and using paraformaldehyde?

[rolnor]

Nice with some NMR-spektra!
You should follow the procedure EXACTLY, why it did not work can be difficult to say but use the same reagents and try again.

[hollytara]

Those are not so easy to distinguish by simple 1H NMR.  The 1,2,3 substituted vs the 1,2,5 - the major differences are the couplings - for 1,2,3 the H in the middle should couple to both adjacent H's and be a double of doublets - but the coupling constants are the same (more or less) so it may look like a triplet. The other two H's couple to the middle one and then weakly to the other - look like doublets of doublets.   The 1,2,5 has two H3 and H4 ortho to each other and H6 is para to H3 and meta to H4.  H4 should be a real doublet of doublets.  H3 and H6 simple doublets - with different coupling constants.  (ortho coupling larger than meta, para effectively 0)

The resolution on your NMR is not enough for me to tell here. - but you can probably see it. 

[Ion.liq]

Those are not so easy to distinguish by simple 1H NMR.  The 1,2,3 substituted vs the 1,2,5 - the major differences are the couplings - for 1,2,3 the H in the middle should couple to both adjacent H's and be a double of doublets - but the coupling constants are the same (more or less) so it may look like a triplet. The other two H's couple to the middle one and then weakly to the other - look like doublets of doublets.   The 1,2,5 has two H3 and H4 ortho to each other and H6 is para to H3 and meta to H4.  H4 should be a real doublet of doublets.  H3 and H6 simple doublets - with different coupling constants.  (ortho coupling larger than meta, para effectively 0)

The resolution on your NMR is not enough for me to tell here. - but you can probably see it.

I analyzed a few publications and supplementary info. I think, that my obtained product is 3-(Chloromethyl)-2-hydroxybenzaldehyde.
All the time I thought, that I obtained 5-substituted product because I made it using preparation for 3-substituted compound.

[hollytara]

That is definitely 1,2,4 subsitution.  (yours is numbered 1,2,5 because aldehyde has naming and numbering priority - but as a generic substitution pattern it is 1,2,4).

See it here:  https://hatsudy.com/nmr-b.html

If you had 1,2,3 substitution you would not see this pattern.  Instead - a fuzzy triplet for H5, and the doublets of doublets for H4 and H6. 

ChemDraw will predict it for you - reasonable but not perfect.

[Ion.liq]

That is definitely 1,2,4 subsitution.  (yours is numbered 1,2,5 because aldehyde has naming and numbering priority - but as a generic substitution pattern it is 1,2,4).

See it here:  https://hatsudy.com/nmr-b.html

If you had 1,2,3 substitution you would not see this pattern.  Instead - a fuzzy triplet for H5, and the doublets of doublets for H4 and H6. 

ChemDraw will predict it for you - reasonable but not perfect.

So what I thought at the beginning I have 5-(Chloromethyl)-2-hydroxybenzaldehyde
Now I need to prepare 3-(Chloromethyl)-2-hydroxybenzaldehyde

Thank you all for your help

[rolnor]

I wonder if this is correct, two doublets and one double doublett, is that not what you want? Do you have mp?

[Ion.liq]

I wonder if this is correct, two doublets and one double doublett, is that not what you want? Do you have mp?

I need to prepare 3-(Chloromethyl)-2-hydroxybenzaldehyde (PHOTO1), but all experimental procedures lead to 5-(Chloromethyl)-2-hydroxybenzaldehyde (PHOTO 2)
MP my compounds is 84-86°C (this is mp 5-(Chloromethyl)-2-hydroxybenzaldehyde)
All experimental procedures are almost the same, so still I'm looking...

[rolnor]

Its strange,  the nmr, is the doublet at 7ppm cdcl3? They have nmr in your reference, have you checked that? This is a published compound, get proper nmr-data and/or repeat the procedure exactly.

[hollytara]

You can buy the 3-methyl salicylaldehyde commercially - would radical chlorination work (N-chlorosuccinimide and benzoyl peroxide, for example)?  The phenol might interfere - might have to protect it - but you would get the 1-2-3 trisubstitution guaranteed.