[ugradstudent]

Hi, in class I'm doing a Suzuki Cross Coupling reaction based on
"Nickel-Catalyzed SuzukiMiyaura
Couplings in Green Solvents" by Stephen D. Ramgren, Liana Hie, Yuxuan Ye, and Neil K. Garg.
The reaction involved the bromo-aryl reacting with the boronic acid in heated t-amyl alcohol in the presence of NiCl2(PCy3)2 and tripotassium phosphate.

During the work-up, the first thing we did was transferred our solvent into a test tube of 1M HCl. The product is supposed to be in the aqueous layer, but I don't know how a biphenyl product would dissolve in the aqueous layer.
Can someone clear this up for me? Thank you.

[Dan]

During the work-up, the first thing we did was transferred our solvent into a test tube of 1M HCl. The product is supposed to be in the aqueous layer, but I don't know how a biphenyl product would dissolve in the aqueous layer.
Can someone clear this up for me? Thank you.

1. t-Amyl alcohol is quite soluble in water so I'm a bit confused here - you say there were two phases at this point, are these phases water and t-amyl alcohol or did you introduce another organic solvent as well.

2. Why is the product "supposed to be in the aqueous layer"? Who says that's where it is?

3. As for which layer the product is in, that depends on R¹ and R² - can you tell us what they are?

[ugradstudent]

1.) I didn't add anything new to it. I just took the reaction mixture and put it in 1M HCl.

2.) The procedure of "Nickel-Catalyzed SuzukiMiyaura
Couplings in Green Solvents" that I'm basing the reaction on put the reaction mixture in 1M HCl.
Then, it stated that the layers were separated; the aqueous layer was extracted with EtOAc 3 times. The combined organic layers were washed with brine, dried and passed through a SiO₂ plug.

3.) The compounds I was assigned were bromobenzene and 4-methoxyphenyl boronic acid.

When I added the reaction mixture into the HCl, there were definitely two layers.

[Dan]

Then, it stated that the layers were separated; the aqueous layer was extracted with EtOAc 3 times. The combined organic layers were washed with brine, dried and passed through a SiO₂ plug.

I'm confused - what makes you think the biphenyl is in the aqueous phase? What you have written here means that the organic phase is purified and the aqueous is discarded.

[ugradstudent]

Doesn't it say to extract aqueous layer with EtOAc so we discarded the reaction mixture after adding it to hcl and the product would be moved from hcl to EtOAc.
If the organic layer was wanted, why was EtOAc necessary.

[k1mng]

So the 'layers were separated' comment refers to you taking out and keeping your organic layer which will have most of your product. Ethyl acetate is to extract more of your product from the aqueous in case it's dissolved in there with t-amyl alcohol I guess.

So yeah, never chuck the organic layer in organic chemistry..

[Dan]

When a compound is partitioned between organic and aqueous phases, it becomes distributed between both phases. The distribution is not binary - it isn't either in the organic or the aqueous, it is present in both (see partition coefficient), but usually there is a preference for one phase over the other.

If the organic layer was wanted, why was EtOAc necessary.

For the biphenyl you mention, it will have a strong preference for the organic layer, but some will be in the aqueous layer (remember the aq is saturated with t-amyl alcohol). The purpose of the EtOAc extraction recover the traces of biphenyl that remained in the aqueous after the first separation.

Doesn't it say to extract aqueous layer with EtOAc so we discarded the reaction mixture after adding it to hcl and the product would be moved from hcl to EtOAc.

This was a huge mistake, you threw away the majority of your product.

The prep says:

1. The reaction mixture is added to HCl(aq), then separated. Most of the product is in the organic phase from this step.
2. The aqueous phase from (1) is extracted with EtOAc.
3. The organic phases from (2) and (1) are combined, washed with brine and purified.

[ugradstudent]

Ah, k. Thank you for clearing it up.
Looks like I got to pay attention to the vocabulary more and think about the separation from now on before doing them.

Also, I have a question about the selectivity of this reaction that I posted in
http://www.chemicalforums.com/index.php?topic=79513.0