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I am conducting a synthesis involving Buchwald-Hartwig coupling. The starting materials are 2,3,5-tribromothiophene (MW=320.83) and 1-aza-18-crown-6 (MW=263.33). I used $\ce{Pd_2(dba)_3}$ (MW=915.7) as catalyst, tBuXPhos (MW=424.64), and NaOtBu (MW=96.1) as base. After running the reaction at 80 ℃ during 24 h, the solvent (toluene) turned brown, and first decanted toluene layer using water. Below is the spectrum of decanted toluene layer after filtration and drying. (named Sample3-Oil)

spectrum1

And I also separated rest of the toluene layer by separatory funnel. Below is the spectrum of separated toluene layer after filtration and drying. (named Sample3-Sep) Seems similar to the first spectrum. specrtum2

It seems that m/z=115, 120, 142 peaks are from methanol, which is used as mobile phase in MS. I presume that m/z=264 peak is 1-aza-18-crown-6 and m/z=286 peak is [1-aza-18-crown-6+Na]$\ce{^+}$. As far as I know P ligands are slowly oxidized during reaction, forming P=O bond. So I presumed that m/z=442 peak is oxidized tBuXPhos (424+16=440≈442). Also this peak was increased after drying the sample, simultaneously m/z=425 peak disappeared. Because the molecular weight of wanted product is 503.25, I expected that m/z=505 would be the peak of the product.

Meanwhile, I also requested MS of the sample which mixed Pd catalyst and P ligand, stirred overnight at 80 ℃. (named Sample0)

spectrum3

This spectrum also has m/z=505 peak. Therefore I requested MS/MS to determine whether this peak is from the catalyst/ligand or product.

spectrum4 spectrum5 spectrum6

In the MS/MS spectrum of m/z=445, one can observe the loss of iPr(m/z=402) and tBu(m/z=388), so it might be oxidized tBuXPhos. The m/z=505 peak of Sample0 has several fragments while that of Sample3-Oil and Sample3-Sep have only one fragment. But they have m/z=425 peak in common. I think this might be the peak of tBuXPhos (MW=424.64). Does this interpretation seem correct? Then should I judge that the reaction was not successful? One alternative interpretation might be loss of Br, but I'm not sure that this is correct interpretation.

----------------- +) additional spectrum

Sample1-Oil (decanted toluene layer right after the reaction) spectrumadd1

Sample2-Oil (filtered through Celite, and rotoevapored) spectrumadd2

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Krang Lee
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    I would certainly expect a very strong peak from the oxidised phosphine ligand and I would not expect to see much unoxidised ligand. Your 425 could be loss of Br from the product, does the peak show the expected isotope split from the remaining Br present? – Waylander Feb 23 '22 at 07:49
  • @Waylander I added additional spectrum. My desired product has 2 Br, so there would be 1:2:1 isotope peaks, but I can't clearly say the existence of Br isotope peaks. Actually I have once requested the MS experiment of standard 2,3,5-tribromothiophene expecting Br isotope peaks, but there were not. (https://chemistry.stackexchange.com/questions/155648/why-is-the-base-peak-of-my-ms-spectra-of-2-3-5-tribromothiophene-at-m-z-382) – Krang Lee Feb 23 '22 at 08:01
  • @Waylander Although the reason that if m/z=425 is really tBuXPhos then why there are no m/z=425 peak in Sample0 is somewhat weird, but without that assumption I can't explain why m/z=425 peak exist in Sample1 and Sample2 but don't in Sample3. Sample3 is vacuum-dried Sample2 (130 ℃, nearly 24 h). I thought that in the process of vacuum drying the remaining tBuXPhos is totally oxidized. – Krang Lee Feb 23 '22 at 08:19
  • I think it unlikely that the 425 is tBuXPhos. These phosphine ligands usually completely oxidise by the completion of the reaction. – Waylander Feb 23 '22 at 08:24
  • @Waylander Hmm.. Then I think I should check the MS/MS fragments of m/z=425... – Krang Lee Feb 23 '22 at 08:28
  • @Waylander Can I ask one more question? I requested MS/MS analysis of m/z=425 using ESI, and it resulted no fragmentations at all. Just m/z=425 itself alone. Then how can I interpret it? At least definitely it seems that it is not tBuXPhos. – Krang Lee Mar 11 '22 at 01:03
  • Difficult to know what it is then. If it were loss of Br from the product I would expect further fragmentation (loss of the second Br perhaps). I am not a MS expert. – Waylander Mar 11 '22 at 06:25

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