Dear friend Mohamed Ali Aloui

It’s great to hear about your progress with the propargylation experiments. Your methodical approach really stands out, and I appreciate the level of detail you’re putting into optimizing the reaction.

A few thoughts came to mind that might help guide your next steps. First, while your use of an ice bath followed by room temperature is a solid start, you might see improved conversion by extending the reaction time at a slightly elevated temperature. Also, although bromide is a reasonable leaving group, switching to a tosylate could enhance your reaction efficiency—converting your propargyl bromide to a tosylate might be worth a try.

Regarding solvents, THF is generally suitable, but experimenting with DCM or DMF could yield different results, especially if solubility or reaction rate becomes an issue. For the base, TEA is a good choice, but make sure you’re using it in excess to neutralize all generated acids. If you encounter difficulties, stronger bases like DBU or potassium carbonate might help.

Your NMR observations are promising, especially the new peaks in the ¹H spectrum. If the ¹³C NMR isn’t showing much, it could be a sensitivity issue—consider increasing the number of scans or using DEPT or 2D NMR techniques for more clarity. Running control experiments with model compounds bearing only -OH end groups could also provide clearer insights into your reaction’s efficiency.

I hope these suggestions are helpful. Please feel free to reach out if you’d like to discuss further or need more ideas. Wishing you the best of luck with your experiments!

Best regards,

Kosh

Dear Kaushik Shandilya,

Thank you so much for your kind message and for taking the time to respond with such thoughtful suggestions. I really appreciate your words it means a lot!

What you mentioned is very helpful. I had actually been considering using a tosylate derivative or a different propargyl agent with a better leaving group, so your suggestion resonates with the direction I was thinking of taking. I’ll definitely look into synthesizing or sourcing such a compound and testing it out.

I also noticed some changes in the proton NMR when extending the reaction time, which seems promising, so I’ll keep pushing in that direction. As for the 2D NMR and possibly DEPT, I agree it’s worth a try—thank you for the reminder! Hopefully, with these optimizations, I’ll get a clearer picture and better conversion to confirm the functionalization.

Thanks again for your support and insight and please don’t hesitate to share any other thoughts that come to mind!

Best regards, Mohamed Ali

A quick look in the literature suggests it may be difficult to get quantitative functionalization and one even suggests tosylating the hydroxyl groups first and then using propargyl amine as a more activated approach to place the alkyne group on.

In terms of the NMR method sensitivity- the alkyne group will have one carbon with no protons on it and one carbon with only one proton on it. The C13 relaxation rates for these carbons will be slower than alkanes with more more hydrogens on them. This could lead to apparent lower alkyne C13 peak intensities- unless you use longer relaxation times in the experiment set-up. Depending on the polymer molecular weight- looking for peaks from end groups can be difficult. Would trimethyl silyl chloride functionalization be a possibility? (handling the silyl ether due to its limited hydrolytic stability (might be a challenge) but having 9 protons to look for in the NMR might be advantageous. Or adding t-butyl groups would add 9 protons. Either of which would make finding and quantitating them in the NMR easier.

Dear Steven D. Smith ,

I've been thinking carefully about the intensity of the three peaks I aim to observe in the 13C NMR spectrum. As I mentioned, I did observe the two interesting peaks corresponding to the newly added protons — specifically, the two protons adjacent to the oxygen in the polymer backbone, as well as the terminal CH proton peak.

However, I was struggling to clearly identify the three carbon peaks associated with the added alkyne group. Some signals appeared, but their intensities were quite low, which made interpretation difficult. What you mentioned is insightful and aligns with my own thoughts — I expected to see more intense, well-defined peaks for these carbons.

My main goal is to introduce an alkyne end-group into my polymer, which has a molar mass of approximately 3000 g/mol. The use of a tosylate is indeed something I’m considering for facilitating this transformation.

I truly appreciate your guidance — it has been very helpful. You're absolutely right that kinetics plays a crucial role here. I will be sure to keep you updated on the results as my work progresses.

Best regards, Mohamed Ali

I was thinking more about the NMR and remembered that even with proton NMR when we ran ethanol and isopropanol as samples we saw integration ratios noticably off from 3/2 (EtOH) or 6/1 (IPA). We found the pulse delays around 1 second and started a few experiments where we lengthened the pulse delays. I think it was significant - adjusting from 1 sec to 30 sec until we were happy with the quantitations. And your tertaiary carbon would be even slower. Maybe try t-butanol as a sample. Ultimately- a small molecule synthesis of propargylated ethanol or propargylated isopropnaol and the NMR experioment to confirm you get quantitative integrations would ensure all of the carbon structures in your samples will have a chance to relax -allowing for quantitative results in your polymer experiments.

Here are some potential explanations and suggestions based on your experiment generated by AI:

🔬 1. Low Conversion as Likely Cause of Weak ¹³C NMR Signals

The absence of new peaks in the ¹³C NMR — despite some in the ¹H NMR — most likely reflects low degree of end-group modification, not the complete absence of reaction. Since the signals from end groups can be inherently weak in polymers, even a 5–10% functionalization may give discernible ¹H NMR signals but fall below detection threshold in ¹³C NMR due to lower sensitivity and overlapping polymer background.

• Try quantitative ¹³C NMR with longer relaxation times and more scans (if feasible).

• Alternatively, derivatize the propargyl group with a UV- or fluorophore-active azide via click chemistry. This allows quantification via UV/vis or fluorescence and can be used to back-calculate conversion.

🧪 2. Bromide Is a Mediocre Leaving Group in This Context

While propargyl bromide can react with alcohols, it may not be sufficiently reactive under mild conditions — especially in the presence of competing unreactive methyl end groups.

• **Consider using propargyl mesylate or tosylate instead. These are better leaving groups and may significantly improve the reaction kinetics and selectivity for –OH ends.

• Alternatively, use propargyl alcohol with DCC or CDI to form the carbonate or ester in situ, enabling more selective activation of the hydroxyl end groups on the polymer.

⚗️ 3. Reaction Conditions and Optimization

• THF + TEA is a reasonable choice, but:

• Did you dry your THF thoroughly? Moisture can compete and quench electrophile.

• TEA may form a tight ion pair with the leaving bromide, potentially hindering reaction. Try DIPEA (more hindered) or inorganic bases like K₂CO₃ if solubility allows.

• Prolonging the reaction time may actually be less useful than increasing temperature slightly (e.g., to 40–50 °C) after initial cooling period, which can improve nucleophilic substitution rates.

🧬 4. Confirming Selective Functionalization

Given that only some chains have OH ends, you are inherently working with a mixed system. This limits conversion even under ideal reaction conditions.

Suggestions:

• Run a model reaction with a small-molecule analogue (e.g., benzyl alcohol) under the same conditions — this can validate your system reactivity independently from polymer complexity.

• If possible, use MALDI-TOF to check for mass changes in polymer chains, which can offer another confirmation of end-group modification.

Summary Recommendations:

Issue Suggestion

Weak ¹³C NMR - Use qNMR, derivatization, or MALDI-TOF

Low reactivity of bromide - Switch to mesylate/tosylate or activate OH differently

Mixed end groups - Consider pre-fractionation or statistical modeling of conversion

Reaction inefficiency - Improve drying, base choice, and consider mild heating

If you share your ¹H NMR data or polymer MW, we could help further in estimating conversion from integrals.

Good luck — this is an interesting problem with real synthetic subtlety!

If permitted you can activate the -OH functionality

Dear Steven D. Smith Yevhen Yekymov Asit Baran Samui ,

I thank you for your follow-up. Adding more pulse delay is something I should try. I already performed a propargylation of my diol starting monomer, just to try to observe the peaks on the ¹³C NMR spectrum. I work under dry experimental conditions — whether it's the solvent or the TEA, the propargyl bromide, or my sample (whether it's my polymer or the last experiment with the diol), everything is always put under vacuum before introducing the solvent THF.

My polymer molar mass is around 3000 g/mol, but what could be problematic is the variability in chain ends — with -CH₃, -OH, on each or both sides. What I also understood from what you mentioned is the -OH reactivity and the leaving potential of the -Br group. This still remains an open question: whether I should use tosylated propargyl or further activate the hydroxy end group.

As for the kinetics, I would really like to confirm that extending the reaction time to three days (instead of overnight) makes a difference, because the peaks I observed in the proton NMR only appear in the three-day experiment. You can also see the salt at the bottom of the flask and the organic phase above it.

Again, I really thank you for your guidance! I’ll keep you informed of the latest results — any advice is highly appreciated.

please be aware that the answer was generated by AI with the aim of development of the discussion or new points of view, not as a solution. mistakes, hallucinations and the lack of accuracy can take place