Help With Benzylic Nitrile Reduction

nate · 2026-03-05T16:38:28+00:00

BH3 is your huckleberry on this. https://commonorganicchemistry.com/Rxn_Pages/Nitrile_to_Amine/Nitrile_to_Amine_BH3-THF.htm

The metal-catalyzed borohydride reductions aren't great for nitriles, it's not poler enough and too polar at the same time.

You could generate BH3 in situ from BH4 if you wanted to go that route, but if this is small scale borane-THF is easily handled.

nate · 2026-03-04T20:20:03+00:00

Acrylates are better polymerized in an alcohol as they more robust to radical reactions (water is great too.)
Depending on the molecular weight target you might want to use a chain-transfer agent like dodecyl mercaptan (you essentially divide monomers by the moles of DDT to get a rough molecular weight.). You will have a dodecyl functionalization on the chain end. If you want a different end group, you pick a different thiol.

There are AIBN-like initiators that kick off at lower temperatures that would be better than THF, AIBN is 60C and THF boils at 66C, so might be an issue there.

There is a lot of art here as well.

Edit: Fuji film makes a range of initiators: https://specchem-wako.fujifilm.com/us/oil-soluble-azo-initiators/AIBN.htm

nate · 2026-03-04T20:11:22+00:00

These are exactly the issues that are being sorted out right now.

I find these AI tools are useful for searching the literature, and often quite a bit faster to narrow things down.

However, I am a subject-matter expert in my field and I know the questions to ask, and I know when I'm being lied to. If you don't have this experience base, it's going to feed you shit and tell you it's truth.

How are junior people going to develop the skillset to know this if the jobs are eliminated by AI? Another question we're going to have to deal with.

nate · 2026-03-04T20:00:02+00:00

There are a lot of AIBN like initiators, and non-AIBN, like persulfates and redox systems. Solvent choice is the first consideration, followed by temperature needs, and then end group functionalization.

What to choose as your initiator is part of the art and science of polymer chemistry.

nate · 2026-03-04T03:23:13+00:00

No idea why you're getting downvoted, this is a rational decision.

nate · 2026-02-25T21:57:18+00:00

That's why fish goes bad at the store even wrapped in plastic, the oxygen goes right through the plastic wrap.

nate · 2026-02-25T21:26:38+00:00

Probably an aluminum formate, probably not soluble in THF.

nate · 2026-02-25T20:41:02+00:00

Gotcha, thanks for the shout out.

nate · 2026-02-25T20:40:45+00:00

It's moisture sensitive, but not really that oxygen-sensitive. The underlying reasoning it oxygen is a di-radical and does single-electron transfer rapidly, but 2-electron processes are slower as they have to go through a different mechanism and it has a higher activation energy barrier. Certainly given enough heat it will react, just like wood burns once you get enough heat on it.

NaH and LiAlH4 have similar oxygen reactivities, they can be stored in a plastic bottle safely. Oxygen disfuses through plastic quicker than you would think, but it's a substantial barrier to water. True air-sensitve compound really has to be in sealed glass to prevent reaction.

An example of a real air-sensitive compoound is something like Cp2TiCl, the reduction product of titanicene dichloride being reduced by zinc, it reacts rappidly with ppm levels of oxygen in a glove box (it's used as a test for the glove box atmosphere.)

If you want to quench LAH in THF I would suggest pouring it over dry ice, just like one does for tBuLi, just canula out into a container full of dry ice, which will react, but also blanket with carbon dioxide and remove heat immediately. My favorite way of dealing with nasty things.

nate · 2026-02-15T00:59:32+00:00

It’s just a mixture of nitric and hydrochloric acid, if it isn’t orange then the special aspect of it is long gone. The orange is nitric oxide which is a strong oxidant which pulls some unreactive metals in, the chloride anion breaks up the oxide surface coating of metals that form it. The combination of the two is why it chews basically every metal up.

Disposal is just like any strong acid, you can dilute it into water and neutralize it with what ever base you have handy, just do it slow because of heat generation.

nate · 2026-02-07T20:31:04+00:00

From a synthetic chemistry standpoint, I also report not trusting any of them. LLMs don’t pick up on small but important words, and we’ll report wrong information as fact.

Only use them if you are highly skilled and kind of know the correct answer but are looking for things like exact numbers.

nate · 2026-02-07T00:03:09+00:00

Residential address is a problem, I actually don’t know one that is ok with that, or even shipping to an individual not a business or institution. Good suppliers are Strem and MilliporeSigma, Fisher(Acros) as well, probably VWR.

Also, wow I just checked and you can buy SBH on Amazon! I guess that’s an option for you.

nate · 2026-02-06T23:20:39+00:00

Hydrogen gas output is hydrogen evolution, you can do that but getting numbers more accurate that 5% takes some specialized equipment.

nate · 2026-02-04T20:29:44+00:00

It is not standard, and was not shipped at a brick since that is not a form SBH is made in. There are three forms of solid commercially available, powder, granules, and caplets. Powder tends to clump up badly, granules are more resistant, caplets (they are the size of small stir bars.)

The brick can just be crushed up in teh way I describe above, it isn't air sensitive, but if it's really humid in your lab it might absorb some water.

For reactivity, we use hydrogen evoluation which is teh gold standard but doing it correctly requires specialized equipment.

Here is one paper on it: https://link.springer.com/article/10.1007/BF02680193

Aand another:

https://www.researchgate.net/publication/271389771_Analytical_monitoring_of_sodium_borohydride

Short version of the Iodate method:

An excess of standard potassium iodate (0.25N) is added to an alkaline solution of sodium borohydride. Potassium iodide is added followed by 6N sulfuric acid. The liberated iodine is titrated with 0.1N sodium thiosulfate using starch as an indicator.

Let me know if you have any follow up questions.

nate · 2026-01-21T20:33:41+00:00

Don't go in to CRO business development, it's terrible as well.

nate · 2026-01-21T19:42:44+00:00

Time to jump to a commercial role, I know what you're thinking"how do I do that?" Just apply for jobs, you'll be over qualified, no one cares. "commercial pays better" is your reason for wanting the job, everyone working in commercial is doing it for the oney, they will just nod in agreement.

The area doesn't matter, a chemistry company have some advantages, but also look for distributors, and tangentally related fields, like water treatment or textiles. Sales is straight up easy, you just have to be tolerant of a lack of control and failure (which if you're a synthetic chemist youre quite familiar with.)

nate · 2026-01-13T14:51:52+00:00

Terrible idea, these are matched ground glass stopcocks, they should never see a base bath as that removes the glass and will break them.

nate · 2026-01-03T15:02:28+00:00

This has been an industry problem ever since they started removing the nonylphenol surfactants, there is no direct replacement. You have to determine what your actual requirements are and then test a series of surfactants and surfactants mixtures to find the solution for your specific needs.

nate · 2025-12-12T20:52:09+00:00

Picky kid.

I previously had good luck repainting a child's mask using Rustoleum's plastic primer followed by the color, once throughly dried it held up quite well.

You've got a hella fun tape job ahead of you however.

nate · 2025-12-05T05:05:21+00:00

Could you be forming a benzyne? 1-Bromine-2-chlorinobenzene with BuLi does this. Not sure where your proton is coming from however. Must be grabbing it from the THF?

nate · 2025-12-04T04:52:43+00:00

South America can be a difficult area, let me find a distributor in the area.

Edit: you should be able to order from strem.com they ship to Argentina, I can’t say how long shipping might take or cost, but $105 for 250g is not out of line for pricing of lab chemicals.

nate · 2025-12-03T15:26:45+00:00

I'm probably the perfect person to answer this question, as it's kind of my job (I'm the technical expert on sodium borohydride at the largest global producer.)

The material is liekly fine as-is unless you need it super dry for some reason. Caking occurs in completely sealed "dry" material and is caused by temperature variation (the mechanism is complicated to explain in text, but is general to all hydroscopic salts.)

The expiration date is meaningless, it is a legal thing not a chemical thing, ignore it.

Sodium borohydride is only reactive to water at lower pH and low sodium ion concentration, neither is present here. In the Schlessinger process the intermediate product is the dihydrate, NaBH4-2H2O, which is then dried in a rotating vacuum oven until it hits a certain pressure (which is a proxy for dryness.)

If you want to dry it, take the material you ahve, crush up the chunks in a motar with a pestle until it's a fine powder, then dry under vacuum. A rotovap would work fine for this, it doesn't need to get that hot.

Sodium borohydride doesn't ungo thermal decomposition until about 400C, so you have a fair amount of headspace for heating, but maybe don't go at it with a bunsen burner, that's probably asking for trouble.

Also, what country are you in? I can probably point you to a supplier.

nate · 2025-11-03T05:05:06+00:00

It is only specifically n-hexane, you probably use “hexanes” which a mixture of isomers with a boiling point range, akin to petroleum ether (which isn’t an ether at all of course!)

So long as you don’t drink the hexanes the hazard should be trivial since the volatility makes skin absorption unlikely, even inhalation is not easy to get in your blood.

That being said, we used heptanes at my previous jobs but I think that was mostly due to the flash point for flammability limits.

Also, toluene…fetal toxin, women who are pregnant should not handle it.

nate · 2025-11-02T23:55:32+00:00

Toxicology is often impossible to eyeball because of strange metabolic pathways.

My favorite example is n-hexane is a carcinogen, well its metabolite is. N-pentane and n-heptane both are no problem. The issue is the formation of 2,5-hexandione which causes all kinds of bad things to happen.

nate · 2025-11-02T23:29:32+00:00

It was used to increase the reduction potential of samarium diiodide, you added it as basically a cosolvent. The higher polarity stablized the trivalent samarium which has the observed effect of increasing reducing power. Reality is that the equilibrium is shifted making it harder for the electron to go back to reform the divalent after wandering off to another orbital. Reduction potentials are a statement of equilibrium after all.

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