[gt_engineer]

I have a more conceptual question directed at more experienced synthetic chemists.

Background: I am in my second year of doing undergrad research, which has been pretty heavy in organic synthesis. Generally I've found procedures online or had my research mentor help me with the setup. He assured me that it just takes time to get to the point where you "just know" what equipment and conditions to use for certain reactions.

My vague question: Do you have any general rules for when you decide a reaction needs to run under N2/inert atmosphere? I understand that any reaction that would be contaminated with oxygen or moisture is a good place to start...but I still feel woefully inexperienced as to how you know this might happen. Are there general classes of reactions that always require inert atmosphere?

A more specific question: When running reactions under N2 for my previous mentor, I'd purge the system and exhaust through a bubbler for a bit, then remove the line to the bubbler. We'd do it that way so as not to lose solvent vapor and change the composition of the system. We'd still keep the N2 hose to the Schlenk line attached though. I'm wondering why. Obviously it couldn't keep pumping N2 into the flask or the pressure would keep rising. So is the whole flask+N2 line system all at atmospheric pressure? And if so, why keep it attached at all? Why not just remove the N2 line once it was sufficiently purged? Is this to maintain a constant pressure if the reaction evolves gas or something unrelated to the N2 itself? Sorry if this is a silly question, and as a chemical engineer I feel like I should know better...any clarification would be awesome.

Thanks in advance for your *delete me*

[discodermolide]

Run all your reactions under nitrogen.

As to your second question I have no idea, seems a bit strange to me, why not just turn off the N₂ cylinder? Unless someone else was using the system as well?

[AC Prabakar]

I have a more conceptual question directed at more experienced synthetic chemists.

Background: I am in my second year of doing undergrad research, which has been pretty heavy in organic synthesis. Generally I've found procedures on line or had my research mentor help me with the setup. He assured me that it just takes time to get to the point where you "just know" what equipment and conditions to use for certain reactions.

Do you have any general rules for when you decide a reaction needs to run under N2/inert atmosphere? I understand that any reaction that would be contaminated with oxygen or moisture is a good place to start...but I still feel woefully inexperienced as to how you know this might happen. Are there general classes of reactions that always require inert atmosphere?

Yes.The necessity of the N2/inert atmosphere for a reaction depends on the following:-
1.Moisture/Oxygen required/not required
2.Isolating reaction/contents from normal atmospheric condition
3.Expelling reactant/by product(gas)
The anticipated problems would be:-
1.Impacting the reaction by disturbing the systems,rxn intermediates,active species,etc.
2.Some times safety eg.pyrophoric materials usage in the reaction,etc.

There are some reactions which shouldn't be conducted under N2/inert atmosphere!!!!
eg.hydrogenation(conventionaltype),Oxidation(in which Oxygen supply is more crucial for completion of rxn.)

Coming to your second question:
While making N2/inert atmosphere, if the N2 flow is continuous there is a possibility of evaporation of solvent/reactant/reagent.
hence to avoid this there is a general practice i.e. blanketing the reaction.For this kind of procedure above said procedure would be followed.Of course as you mentioned N2 can be stopped after usage.

[curiouscat]

Run all your reactions under nitrogen.

Though,  not always true,  in a plant setting (esp. since you are an engineer  ). Inerting needs money and hence must be justified.

Typical situations when inerting is done:

(1) reactant, product or catalyst degrades in contact with air / moisture.

(2) Same as (1) but replace "degrades" by "explodes" or "catches fire" or "produces toxic by-products

(3) To keep vapor outside the explosive envelope

(4) Vap. phase reactions whose selectivity is promoted by dilution.

Also note that in many industrial settings steam will be a cheaper diluent than N2.

Some more exotic uses:

(1) N2 sparging can provide moderate agitation when other means are ruled out for some reason.

(2) I've heard of reagents been  charged under N2 pressure into reactors; so think of it as an alternative "pump"

[synthon]

Run all your reactions under nitrogen.

For real?  I have typically only used inert gas for reactions that absolutely req'd it, like when using t-BuLi, making phosphines, etc.  Does it make a noticeable difference for, say substitution reactions where dry solvents are used?  It hasn't been my expeerience.

To the OP's specific question, one reason to keep N2 on throughout is to ensure positive N2 pressure on the system, relative to the atmosphere.  This keeps any air from coming in through any junctions which aren't perfectly sealed.  Also as you mentioned, it keeps the system from being closed, so that you could heat (or evolve gas) without high pressures.

[discodermolide]

This has been my way of carrying out reactions for many years. If you live in a country which has high humidity you will prevent water getting in and disturbing your reaction by keeping a positive N₂ pressure.
Also many catalysts are air and moisture sensitive so you need nitrogen atmospheres to handle them properly.

[Babcock_Hall]

There are people who contribute here with much greater synthetic experience than I have.  However, here are a few general comments.  One, it might be helpful to ask whether a reagent degrades catalytically versus stoichiometrically with water or oxygen.  The former should require greater care than the latter.  Two is the question of the scale of the reaction versus the size of the apparatus.  Three, on the question of keeping an inert atmosphere over a reaction, I sometimes use a Firestone valve so that more N₂ can come in or to let exhaust out.
http://www.aceglass.com/manuals/8766/index.php?page=1

[gt_engineer]

Wow, thanks so much to everyone for the responses! They have given me a lot to think about, and I suppose I will gain more experience with this over time. I might go back and look through my lab notebooks to refresh my own memory as far as rxns I've run under inert atmosphere in the past. Thanks again to everyone for the discussion.

[orgopete]

It is true that in many instances, nitrogen may not be necessary. However, this is a comparatively expert opinion. I advocate using nitrogen (or argon) as a safety measure. If you don't know how pyrophoric a reaction may be, using an inert atmosphere is safer. For example, you can find many reports of lithium aluminum hydride fires. LAH has been quenched many times without a fire. If you did not want to have a fire, use an inert atmosphere. If you are guiding someone in the lab, it is safer to advocate an inert atmosphere to avoid an inadvertent fire.

Re: closed system, again a potential safety issue. Gases can expand and contract much more than liquids and solids. My favorite time to close off a system if I have a vacuum. If there is pressure, then special equipment and a shield is advised.

[curiouscat]

It is true that in many instances, nitrogen may not be necessary. However, this is a comparatively expert opinion. I advocate using nitrogen (or argon) as a safety measure. If you don't know how pyrophoric a reaction may be, using an inert atmosphere is safer.

A lot of the advice also depends on context and scale. It is prudent to inert if it is an unknown or unfamiliar chemistry. With time precautions can be relaxed if deemed unnecessary.

It is also a cost-safety tradeoff. In the lab it is fine to be conservative. In the plant OTOH inerting costs a lot of money and needs to be carefully justified. (OTOH an explosion costs even more money!  )

[discodermolide]

In the plant NO reaction is done without inertisation. When it comes to plant safety there is no cost trade off at all. Indeed when it comes to any safety issues there is no cost trade off.


A reaction should always be run under an inert atmosphere.

[curiouscat]

From UK Health and Safety Guidelines:

Inerting is normally only considered when the flammable or explosive hazard cannot be eliminated by other means i.e. substitution of flammable material with non-flammable, adjustment of process conditions to ensure substances are below flammable limits.

http://www.hse.gov.uk/comah/sragtech/techmeasinerting.htm

[discodermolide]

Everything must be inert. When you use different materials, for example a solvent and a glass reactor you will get a static build up which will eventually earth itself. This spark will have enough energy to ignite a mixture, especially when the explosion limit in air is around 7-8% or perhaps less. The electrostatic discharge can also cause decomposition of non-flammable materials to flammable ones.
Adjustment of process conditions? How do think they achieve this? Work in a vacuum? Get rid of the oxygen? How do you remove air/oxygen from a reactor? You evacuate it and release the vacuum with nitrogen.
I say again, No plant I have seen and that's many do not inert their reactors. Not do this would be plain stupidity.
I find this a rather unfortunate thing for the UK authorities to print, especially the health and safety people, who should know better. It is irresponsible to propagate this attitude.

[curiouscat]

I say again, No plant I have seen and that's many do not inert their reactors. Not do this would be plain stupidity.

I have definitely not seen as many plants as you have; so you must be right. I yield.

[discodermolide]

It's not about being right or wrong it's about common sense. When using chemicals on scale everything needs to be handled in an inert atmosphere.
For example, if you do an Evans aldol reaction, the removal of the oxazolidinone auxiliary is usually carried out in THF with lithium peroxide, generated from hydrogen peroxide and LiOH. Here you get lots of oxygen generated by the base induces decomposition of hydrogen peroxide, in fact some 80% of the H₂O₂ used ends up as water and oxygen. This, if not done under a nitrogen atmosphere will lead to an explosion. The only way to do this in a plant is to blow nitrogen through the reactor at some high rate such as 10-20 cubic meters per hour, this keeps the oxygen generated under the explosion limit. Somewhere on my computer I have a diagram showing the O₂ formation from this system. If I find it I will post it .

Always do your reactions under an inert atmosphere.