Yield Difference Between Chloro and Iodo?

[CryoThio]

Can anyone speak to the difference in yield between 2 chloro 4 methylpropiophenone and 2 iodo 4 methylpropiophenone?

Aby other changes in the reaction, perhaps?

 

[BlueDex]

The 2-iodo-4-methylpropiophenone is a better leaving group, but it's harder to get it on the carbon in the first place. The 2-chloro-4-methylpropiophenone is easier to get on the carbon, but a worse leaving group. 2-Bromo-4-methylprophiophenone is just right. Trying to make 4-MMC or 4-MEC?

 

[CryoThio]

The 2-iodo-4-methylpropiophenone is a better leaving group, but it's harder to get it on the carbon in the first place. The 2-chloro-4-methylpropiophenone is easier to get on the carbon, but a worse leaving group. 2-Bromo-4-methylprophiophenone is just right. Trying to make 4-MMC or 4-MEC?

BlueDexEventually trying to make 4 mmc, but also use precursors that are not on any list whatsoever.

2b4m is on such a list, even if it is a very unenforced one. It is still technically not ok to own.

2i4m and 2c4m don't have this same issue. Thus me asking about their yields and any differences.

Imo, being as legally cautious as possible is the most important thing, then physical safety, then purity of the compounds.

 

[mushr]

Short response to OP's question: For 2 chloro 4 methylpropiophenone (2c4m), some changes are required in your reaction.

From my experience of adapting the Chinese patent WO2017211129A1 for mephedrone with 2c4m as an intermediate, it took a while before I reached 70+% yields for mephedrone from 2c4m.

It's stated in the patent that they get 40% yield with aqueous solution of methylamine, however please keep in mind that the patent is for unsubstituted methcathinone. For mephedrone, with aqueous methylamine solution, I never got more than 30% yield. By increasing temperature or the reaction time, we can get more of isomephedrone-contaminated product only.

To get 70+% yields of mephedrone from 2c4m, we need to prepare methylamine solution in one of suitable anhydrous solvents as explained here:

How to properly generate Methylamine gas to Methanol

I have problem because I don't know how to properly generate Methylamine gas I putted 100 grams of Methylamine in 80g of water and mixed in one beaker Then I putted 200 grams of NaOH in erlenmeyer flask which was connected with silicone tubing to ice cold liebig condenser and then to Jar that...

bbgate.com

For this particular reaction, all of these methylamine solutions worked well for me: 10-20% in Benzene, 10-20% in Toluene, 10% in DCM, 10% in NMP.

I never tried methanol or IPA methylamine solutions cause it's stated in literature that alcohol solvents should be avoided for the methylamination reaction. Would be interesting to see what happens though.

 

[w2x3f5]

Short response to OP's question: For 2 chloro 4 methylpropiophenone (2c4m), some changes are required in your reaction.

From my experience of adapting the Chinese patent WO2017211129A1 for mephedrone with 2c4m as an intermediate, it took a while before I reached 70+% yields for mephedrone from 2c4m.

It's stated in the patent that they get 40% yield with aqueous solution of methylamine, however please keep in mind that the patent is for unsubstituted methcathinone. For mephedrone, with aqueous methylamine solution, I never got more than 30% yield. By increasing temperature or the reaction time, we can get more of isomephedrone-contaminated product only.

To get 70+% yields of mephedrone from 2c4m, we need to prepare methylamine solution in one of suitable anhydrous solvents as explained here:

How to properly generate Methylamine gas to Methanol

I have problem because I don't know how to properly generate Methylamine gas I putted 100 grams of Methylamine in 80g of water and mixed in one beaker Then I putted 200 grams of NaOH in erlenmeyer flask which was connected with silicone tubing to ice cold liebig condenser and then to Jar that...

bbgate.com

For this particular reaction, all of these methylamine solutions worked well for me: 10-20% in Benzene, 10-20% in Toluene, 10% in DCM, 10% in NMP.

I never tried methanol or IPA methylamine solutions cause it's stated in literature that alcohol solvents should be avoided for the methylamination reaction. Would be interesting to see what happens though.

mushrYou can try to replace chlorine with iodine. As far as I remember, the reaction is carried out in acetone.

 

[mushr]

You can try to replace chlorine with iodine. As far as I remember, the reaction is carried out in acetone.

w2x3f5thanks for the hint, it really make sense. I'll try to react my 2c4m with KI in acetone

 

[w2x3f5]

thanks for the hint, it really make sense. I'll try to react my 2c4m with KI in acetone

mushrperhaps sodium iodide will be better, it all depends on the good solubility of iodide in acetone and the low solubility of chloride in acetone. In any case, if you set up an exchange reaction, it will be very interesting to see your work.

 

[mushr]

perhaps sodium iodide will be better, it all depends on the good solubility of iodide in acetone and the low solubility of chloride in acetone. In any case, if you set up an exchange reaction, it will be very interesting to see your work.

w2x3f5thanks, I've got some sodium iodide and I'll definitely try it out as soon as I'm in my lab which is very likely to only happen in mid July. I'll keep you posted here on the progress anyway