[AC Prabakar]

I am trying to couple Primary alkyl halide (Chloro compound)with potassium pthalimide(classic gabriel synthesis).
Up to alkyl halide i conformed the structure.
The coupling of alkyl halide (Chloro compound)with potassium pthalimide was not occurring in my case!!!!
I am using DMF as solvent and taking potassium pthalimide 1.2 eq.
I observed the absence of starting material but not the product(by reverse phase HPLC).
As per literature available the reaction goes via SN2 mechanism(correct me if iam wrong!).
It will be help ful if i got any clarification/the following article:-

"Gabson, M. S.; Bradshaw, R. W. Angew. Chem., Int. Ed. Engl.
1968, 7, 919; Angew. Chem. 1968, 80, 986."



Thanks in advance!!!

[stewie griffin]

I've never done one, although I am familiar with the Gabriel amine synthesis. You say the starting material is being consumed, so I assume that switching to an alkyl iodide probably isn't needed. However, are you seeing any product(s) at all, is it decomposition, etc? It would be helpful to know what the starting material is doing here.
Are you tracking both starting materials for consumption by reverse phase HPLC, or are you just tracking one? It would be helpful to track both. Perhaps the product cospots/coeluets with one of the starting materials.

[OC pro]

Even an alkyl chloride should do the job. Did you try to heat a bit (around 90-100°C). Then you will have progress.

[AC Prabakar]

Thanks for your valuable replies.
I am monitoring both the starting material and for product.I could see the consumption of starting material but not the product!I am seeing some other peak in HPLC.Of course i am trying to characterise that new peak.

It will be helpful if i got some information regarding possible side products in this kind of reactions.

I tried with higher temperature also(up to 120°C).But the results are same.

Two things i have to do.
1.Preparation of pure alkyl halide then proceeding by using that.
2.Finding the possible side reaction and route cause for that.

As an alternate i am trying with other leaving groups also(like mesyl).
information on " possible side products in this kind of reactions" will be helpful.I am also searching!!!

thanks in advance.

[orgopete]

If you gave complete details, it would be easier to make a guess. Neopentyl and benzyl chlorides are primary chlorides, but one should react very slowly. How did you dry your reagents? What scale are you operating on? How did you dry the potassium phthalimide?

[AC Prabakar]

If you gave complete details, it would be easier to make a guess. Neopentyl and benzyl chlorides are primary chlorides, but one should react very slowly. How did you dry your reagents? What scale are you operating on? How did you dry the potassium phthalimide?

Mine is primary alkyl chloride(At beta postion substituted cyclopropane is attached) and it is having 3°amide function in the same molecule.

I am using LR Grade reagents.
DMF-as solvent 0.11% moisture content and potassium pthalimide also LR Grade with LOD below 0.5%.

[OC pro]

Souns like some steric hindrance. Add 1.0equivalents of potassium iodide this will make an "in-situ"-Finkelstein generating the way more reactive alkyl iodide. This should help. DMF in p.A. quality is good enough.

[orgopete]

Because one or both of the starting materials is being consumed, I presumed that a reaction must have been taking place. Further, since phthalimides are notoriously base labile, and water has a low MW, even small amounts of it could lead to opening of the imide ring. Even though only a small amount of water is present, it also depends on the concentration in the reaction. If you assume 0.11% of DMF is water and if this can completely hydrolyze the phthalimide product, what is the stoichiometry of this reaction?

Since it appears as though the reaction is working, or at least your starting material is being consumed, I'd try anhydrous DMSO.