Reductive Amination of Ketones & Aldehydes With NaBH3CN

This organic chemistry video tutorial provides the mechanism of the reductive amination reaction of ketones and aldehydes. It discusses the use of reducing agents such as sodium cyanoborohydride NaBH3CN and sodium borohydride NaBH4 to reduce ketones into amines. The intermediates of this reaction involve a carbinol amine, imine, and an iminium ion. This video contains a few examples and practice problems of ketones with ammonia and a primary amine.

[@TheOrganicChemistryTutor]

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[@johnblacksuperchemist2556]

QUESTION............Since this reaction REQUIRES protons to work. And since protonation is the fastest and has the lowest activation energy to happen. Wouldn't it make more sense to say IN THE FIRST STEP the lone pair on the oxygen on the carbonyl is protonated. And that makes the carbonyl carbon positive enough to accept attack from the NH3 lone pair electrons. And without this protonation of the carbonyl oxygen there would be NO REACTION. And that is why you need a pH of 4 or 5. With a pH of 4 or 5 you can ACTIVATE(protonate) the carbonyl group making it positive enough to even accept attack from a NEUTRAL molecule as long as it has lone pair electrons..........like NH3. Without protonation of the carbonyl oxygen the carbonyl carbon is not positive enough to accept attack from a NEUTRAL molecule even if it does have some lone pair electrons. And that is why you need a pH of 4 or 5 AND WHY THE FIRST STEP SHOULD BE PROTONATION......................IN MY OPINION

[@reynanfielsuyom1415]

Correct :)

[@johnblacksuperchemist2556]

@@reynanfielsuyom1415 ..............cool. Thanks. I think i finally have a pretty good understanding of mechanisms.

[@johnblacksuperchemist2556]

THE ORGANIC CHEMISTRY TUTOR...................Why did you take your video down about the mechanism of reduction of nitro groups to amine groups using metal and acid? Was my mechanism correct and yours wrong and that is why you took it down? Even if it was wrong you should have left the video up. It really taught me and i am sure a lot of other people how to create your own mechanism. Your videos give people a way to think when trying to figure out an unknown mechanism. Your videos are like art man. You do not throw the mona lisa away cause it got a scratch on it. I would have NO CLUE on how to even begin to do mechanisms on more complicated mechanisms IF IT WERE NOT FOR YOU AND YOUR VIDEOS

[@sudhirgir6538]

Bruh relax u spam a lot on his channel omg

[@dianamorad6334]

At 10:32 where does the hydrogen that gets added to nitrogen come from? The hydrogen on the carbon comes from NaBH3CN but what about the one on nitrogen?

[@johnblacksuperchemist2556]

QUESTION.............I see people doing the reaction in DCM and having no proton source like MeOH or water. And they say it takes 30 minutes but if you want to speed it up to 15 minutes or less then just add AcOH for a protons source. So the reaction you said works BEST at a pH 4 or 5. But you never said it had to be at that pH to work. Am i right in assuming the reaction does not NEED a proton source and a proton source just helps speed up the reaction, right???????????????? And the protons flying around would be due to the zwitter ion formed when the carbonyl compound and amine combine, right?????????? I mean the first hydrogen transfer could just be intramolecular, right???????????

[@steepok4806]

if you were to undergo a reaction with an aldehyde could you use PCC instead?

[@johnblacksuperchemist2556]

QUESTION.............If i use MeOH as the solvent(proton source) and put my amine and carbonyl compound in it. Can i also add 3A molecular sieves to soak up the water that formed and SHIFT the equilibrium towards more imine formation and less hemiaminal formation and get ALL imine as the product??????????????

[@johnblacksuperchemist2556]

QUESTION..........DO you have a video on the mechanism for the reaction between NH4Cl and formaldehyde?????? How does the imine become an amine in that reaction??????? It does not make sense.

[@nadiahkhaidir]

at 5:46 what makes oxygen plus charge is it because now oxygen is electron deficient?

[@aaravmodi7595]

at 3:50 why is there no +ve charge on the nitrogen, I am confused is it not supposed to be there

[@erikdejong4509]

NaBH3CN is toxic, so if you use it to create a product. How would you filter out the toxic side products?

[@AmerAlHiyasat]

A negatively charged oxygen cannot exist in acidic solution (it certainly can't exist in the presence of a positively charged oxygen). Your mechanism should start with the formation of a protonated carbonyl, or have OH- as a leaving group and not use acid.

[@shanemichael9011]

You are right. I noticed that also. There is NO WAY that a negative Oxygen will be even somewhat stable in an acidic environment.

[@kinghassan3122]

If it is not under acidic conditions this would be right

[@debbiehariette6335]

I wondered this too

[@promitlahiri4594]

i totally agree, maybe you could use HCl for protonating the carbonyl group.. please rectify if i am wrong..

[@joshuazeldin4040]

Isn’t the ammonium protonating the alcohol also unreasonable since H3O+ is way more acidic than NH4+ and reverse reaction will dominate?

[@erikdejong4509]

Do you need a catalyst in order to react h2nch3 with the ketone?

[@BlackWindowsBW]

If we use H2 gas instead of NaBH3CN with a transition metal like nickel. Will the result be the same?

[@elmyrelebielle3017]

No

[@sudhirgir6538]

Yes, You will get the same product.

[@kshitijverma]

Yeah it'll be same

[@astro8149]

bless you

[@chenfenci4479]

why imine is more electrophilic than ketone? oxygen is more electronegativity than nitrogen

[@oskarford4942]

The imine is protonated as it is in an acidic solution. The positive charge on nitrogen results in a stronger electron withdrawing effect than the aldehyde (the aldehyde would not be protonated but hte imine would be as the imine is a stronger base). This means that in acidic solution the imine is more electrophilic. In neutral conditions when neither species is protonated the aldehyde is more electron withdrawing than the imine as you correctly reason.

[@chenfenci4479]

@@oskarford4942 thank you so much!

[@muhamadmustafa5218]

Thank you so much

[@mortezamirghiasi7259]

Thank's great 👍

[@赵阳-k5p]

thanks a lot

[@jongskyjongsky5883]

How can you have ammonia in an acidic environment?

[@oskarford4942]

Add acid

[@Antonio-wh8lh]

Jongsky Jongsky Try adding ammonium salts? Ammonium salts are acidic if I am not mistaken, not sure if it can get to pH 4-5 though

[@johnblacksuperchemist2556]

Jongsky.................There is always an equilibrium in water. If you have NH3 in water you also have NH4+ and OH in water. Make it acidic by adding HCl acid and now you make NH4Cl. But in water solution it is NH+ and Cl anions and you got H3O+. Well what happens if a NH4+ protonates a water miolecule to make some more H3O+. The NH4+ cation turns into neutral ammonia NH3. And this all happens in equilibrium. There is probably going to be less NH3 in an acidic solution compared to in a alkaline solution but NH3 is there either way

[@missnoodlebrain]

thank you sooo much

[@ytonly3167]

Too gud

[@tahani91kh80]

Can I ask about a mechanism?

[@johnblacksuperchemist2556]

QUESTION.................So if i want my product to be the hemiaminal can i just add a bunch of water to the reaction and SHIFT the equilibrium into more hemiaminal formation and less imine formation????????????????????? If i can do that then how does the reaction work with ammonia in water????????????????????????? Why doesn't the equilibrium get shifted to making all hemiaminal and no imine???????????? Oh wait i think i know the answer to that. The NaBH3CN will not reduce the hemiaminal but will reduce the imine. So even with a lot of water there is still a LITTLE imine and as imine is reduced then more imine is made due to equilibrium, right????????????

[@whoboughtthenoodles]

you changed bro....

[@tahani91kh80]

Hello

[@shrikantpothdar3854]

Sir please talk in hindi

[@drewgamingzone8196]

Idiot no hindi word exist there.

[@Elektrochemistry]

pure anhydrous ammonia?

[@JSFG80]

thanks a lot