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حالت اشکال زدایی انگلیسی Board - Synthesis of 2-Nitropropane-1-Ol - Powered by XMB 1.9.11 (Debug Mode)
حالت اشکال زدایی انگلیسی Board - Synthesis of 2-Nitropropane-1-Ol - Powered by XMB 1.9.11 (Debug Mode)
حالت اشکال زدایی انگلیسی Board - Synthesis of 2-Nitropropane-1-Ol - Powered by XMB 1.9.11 (Debug Mode)
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Synthesis of 2-Nitropropane-1-ol
Hi there!
Posts: 20
Registered: 12-12- I wonder if this interesting reactant could be prepared for example from formaldehyde and
2017 nitroethane by Henry-reaction?
Member Is Offline Do you have any literature about the synthesis of this compound?
Mood: No Mood I was originally interested in the synthesis of 2-Aminopropanol-1-ol, but the synthesis of the
educt seems to be even more interesting
There are tons of literature and patents for this henry-reaction using aromatic aldehydes
instead of formaldehyde to form pharmaceutical percursers but the physical properties of the
substrates are very different, so I doubt the same conitions could be used if Henry-reactions
work at all for H2CO and EtNO2.
Literature; Mundy, Bradford P., Michael G. Ellerd, and Frank G. Favaloro Jr. Name reactions and
reagents in organic synthesis. John Wiley & Sons, 2005. S.300-301
The resin seems to be for removal of Ca2+ cations, without it might more dangerous to destill I
guess!?
Yield is sad, I think I won't try it, at least not this way
[Edited on 25-12-2017 by EilOr]
Seems sensible as this same or similar reaction is used in the prep for 2 nitro ethanol and some
Posts: 319
notorious nitro alkenes.
Registered: 31-8-
2015 This if im not mistaken is the the Henry Reaction.
Location: Noo Z Land https://en.wikipedia.org/wiki/Nitroaldol_reaction
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The calcium oxide forms calcium hydroxide upon hydration with water and this acts as the
Mood: Misanthropic necessary base to deprotonate the alpha carbon and allow it to be attacked by the
formaldehyde.
The use of CO2 for protonation is odd to me but i guess that is to prevent the formation of
calcium sulfate, although i don't see why this is desirable.
Why would you not be able to use NaOH as the base and HCl to protonate is beyond me.
Might i ask why you are preparing 2-nitro-propanol? as its a rather specific product and nitro
ethane is considerably less accessible than most other nitro alkanes.
1. Attempt to re-express your target’s position so clearly, vividly and fairly that your target says:
“Thanks, I wish I’d thought of putting it that way.”
2. List any points of agreement (especially if they are not matters of general or widespread
agreement).
3. Mention anything you have learned from your target.
4. Only then are you permitted to say so much as a word of rebuttal or criticism.
The calcium oxide forms calcium hydroxide upon hydration with water and
this acts as the necessary base to deprotonate the alpha carbon and allow
it to be attacked by the formaldehyde.
The use of CO2 for protonation is odd to me but i guess that is to prevent
the formation of calcium sulfate, although i don't see why this is desirable.
Why would you not be able to use NaOH as the base and HCl to protonate
is beyond me.
Might i ask why you are preparing 2-nitro-propanol? as its a rather specific
product and nitro ethane is considerably less accessible than most other
nitro alkanes.
Hi
Do you have or know any experimental sources that nitroethanol could be made in a decent
yield by Henry-reaction? I thought you would end up with mmostly products like
di(hydroxymethyl)nitromethane or even tri(hydroxymethyl)nitromethane (which might be also
interesting compounds though) due high reactivity of nitromethane.
Would be an interesting read.
I think gassing with CO2 is only to prcp. Ca2+ as carbonate which is easyer to filter out of
solution. Oxalic acid might be maybe an alternative.
HCl and other strong acids like H2SO4 for protonatiion would lead to Nitropropene-side-
products due E1-elemination. Short chained nitroalkenes are extremly reactive, volatile, and
potent toxic lachrymators, they so should be all avoided if possible. So CO2 seems to be a very
smart way to me, as it couldn't harm the sensitive product. Also SN1-side-reactions with HCl
could lead to 2-nitro-1-chloropropane as another side product, lowering the yields and purity.
Nitroethane is easy to get for me - A friend has a very old 250mL glass bottle of nitroethane
from Merck getting yellow-brownish with a little precipitate already forming, I guess it's more
than >40yrs old, collecting dust, so access would be no problem to me at all. I would be scared
of destilling that old stuff as I already saw a fume-off from nitroalkylnates damaged another
colleagues polycarbonate-goggles(!) without hurting that lucky bastard, so I thought it would
would be a great educt compound as it has to be disposed anyway, though with that rather low
yield I could expect I think I won't try it and the EtNO2 will collect dust for another couple of
years
Quote:
Are you talking about me? Could you please explain that?
I didn't ask a single question about any drug related percurser AFAIK, and I don't see how ANY
of the chemicals I mentioned or talked about in this forum would be useful at all for the
synthesis of methadone!? For me asking about 2-nitropropan-1-ol and AlH3/DABCO-adducts as
potential new catalyst seems (use the search engine with my nickname!) to be VERY far fetched
to insinuate that I'm interested in making it or any analogues. Or did I miss something, as I also
don't see how nitropropanol could be used for the synthesis of methadone at all?
Mr EilOr, im fairly confident you are not a drug cook, for one you show a decent understanding
of the field, as evident for you showing a greater understanding for the reaction in question than
Posts: 319
Registered: 31-8- myself.
2015 Also your post history wouldn't seem to suggest anything of the likes either, Im not sure why
Location: Noo Z Land Bert accused you like so beyond the obvious use of this reaction in the production of
Member Is Offline nitroalkenes, it would be a hard push to get to cathinones via this reaction.
Mood: Misanthropic The reason i questioned your target compound however is because it could be reduced to the
amine and the subsequently halogenated to 2-amino-halopropane where it could be attacked by
a grignard reagent or organozinc reagent under controlled conditions to form the obvious
amphetamine.
I do not assume everyone who asks such questions to be a drug cook however i must question
them just to be sure of their intent. This forum gets weird sometimes.
However, in the oh so ironic drug literature there are reports of 85% yields, however these were
performed on arenes such as benzaldehyde.
They do however seem to emphasize keeping the reaction temp below 20*C while adding the
base to the nitroalkane aldehyde mixture.
https://erowid.org/archive/rhodium/chemistry/nitrostyrene.vo...
If we were to take all these write ups at face value then i would assume reaction temperature to
be the main factor affecting yield.
Hope this helps.
@EilOr, follow this recipe. No calcium oxide, nor exchange columns. Simple stir formaldehyde,
nitroethane and K2CO3.
Posts: 349
Registered: 5-5-2016
Location: Latin You'll get 2 nitropropane, 1- ol, substituting 53 grs of benzaldehyde by 40,54 grs of formalin
America (37% formaldehyde).
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Then reduce it with your favorite choice to 2 amino propane- 1 ol:
Mood: Quarantined
Step I: Preparation of phenylnitropropanol
Into a suitable beaker or flask, place 53 grams of benzaldehyde, followed by 37 grams of
nitroethane. Immediately thereafter,
add in 30 milliliters of a 30% potassium carbonate solution, and rapidly stir the entire mixture at
room temperature for 2 hours.
Note: A cold-water bath may or may not be needed to keep the reaction mixture at ambient
temperature (room temperature).
Do not allow the reaction mixture to get above 25 Cel sius. After stirring for 2 hours, add to the
reaction mixture 200 milliliters
of diethyl ether, and shortly thereafter, add in 90 milliliters of a 10% sodium bisulfite solution,
and then moderately stir the
entire reaction mixture for 30 minutes. Afterwards, place the entire reaction mixture into a
separatory funnel , and then remove
the upper ether layer (after removing the lower aqueous layer). Thereafter, wash this upper ether
layer with three 75-milliliter
portions of cold water. Note: after each washing portion, use a separatory funnel to recover the
ether layer, which will be the
upper layer each time. After the washing portion, add to the ether layer, 15 grams of anhydrous
magnesium sulfate (to absorb
water), and then stir the entire mixture for 10 minutes . Then filter-off the magnesium sulfate.
Then, place the filtered ether
mixture into a distillation apparatus, or rotary evaporator, and remove the ether. When no more
ether passes over or is
collected, remove the remaining oily residue (after allowing it to cool to room temperature). This
oily residue will consist of the desired phenylnitropropanol.
[Edited on 2-1-2018 by Chemi Pharma]
Can you prepare 1-nitro-2-propanol by the same reaction using nitromethane and acetaldehyde?
Posts: 1833
Registered: 1-5-2011
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Mood: No Mood
I think so @Boffis, cause Henry reaction runs smoothly between an aldehyde and a nitroalkane.
Posts: 349
Registered: 5-5-2016 The nitro group will always be attached to the carbon that makes the bond. Then, if you use
Location: Latin nitromethane instead of nitroethane, you will get always a terminal nitro group while the
America hidroxyl remains at the alpha position.
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Cause this, reacting acetaldehyde and nitromethane will afford 1-nitro-2-propanol, like you said
Mood: Quarantined and reacting formaldehyde with nitroethane will give 2- nitro- 1 propanol, the isomer.
Must remeber that if we don't use a base, like alkali carbonate, but an amine or ammonium
acetate as a catalyser, we won't get a nitro alcohol but a nitroalkene instead.
Hey, going back to the amine idea, I'd like to suggest the following:
Posts: 39
Registered: 29-12- acetone + morpholine + ammonium iodide + sodium percarbonate
2011
Location: West Coast This will make 1-morpholinylacetone as it only works with secondary amines to make tertiary
Baby amines (unless there's a t-butyl or something similarly bulky).
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If one wanted to go for a more boring target molecule then they could use dimethylamine.
Mood: No Mood Another drawback of making the dimethylamine intermediate though is that it leads to one
useful intermediate and one useless intermediate whereas the morpholino lead to two: one for
phenadoxone and one for dextromoramide.
Anyway, the ketone would of course be reduced to the alcohol (via CTH (Pd/C + potassium
formate in wet methanol), or NaBH4, or SmI2) before being converted to the chloride (SOCl2).
There's an interesting article to check out on SmI2 reductions btw. If anyone would be so kind
as to share this article, this is the link to it:
Reduction of Carbonyl Compounds by Lanthanide Metal/2-Propanol: In-situ Generation of
Samarium Isopropyloxide for Stereoselective Meerwein−Ponndorf−Verley Reduction
Now before anyone replies that I switched the alcohol and amino group from what was
originally requested, that's because 2-chloro-1-whateveraminopropane and 1-chloro-2-
whateveraminopropane react exactly the same in the base catalyzed attack on
diphenylacetonitrile. But, if this whole thread is for some other much more boring purpose
<sigh> then one could use propionaldehyde to get the amine on the 2 position.
Besides ammonium iodide + sodium percarbonate, another way to stick a secondary amine
next to a carbonyl group is with CuBr2 in DMSO with the re-oxidant coming from ambient O2.
Both articles are attached...
Attachment: Cathinones directly from Propiophenones via Iodination with NH4I & Na
Percarbonate.pdf (464kB)
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Attachment: cathinones directly from propiophenones with CuBr2 & DMSO SUPPORTING
INFO.pdf (1.9MB)
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I couldn't get the file uploader to work for one of the files in the previous post so I'm trying again
in a new post...
Posts: 39
Registered: 29-12-
2011
Location: West Coast What the fuck...
Baby
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Mood: No Mood
[Edited on 11-1-2018 by Dope Amine]
/CJ
Attached is proof that NH4I will work with aliphatic ketones as well as aromatic ketones...
Posts: 39
Registered: 29-12-
Attachment: Iodination of ketones with NH4I and Oxone.pdf (3.4MB)
2011
This file has been downloaded 687 times
Location: West Coast
Baby
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Mood: No Mood