Sciencemadness Discussion Board - reduction of carbonyls without NaBH4 and LiAlH4

reduction of carbonyls without NaBH4 and LiAlH4

JoseTineo - 16-6-2019 at 20:41

Can be possible the reduction of a carbonyl with fe/HCl an Sn/HCl SnCl4 instead of NaBH4 and LiAlH4???

DraconicAcid - 16-6-2019 at 21:52

Not generally. You can turn a ketone into a tertiary alcohol (or an aldehyde into a secondary one) by reacting it with a Grignard, though.

Actually, on second thought, aluminum isopropoxide can be used to reduce some ketones to alcohols, if I remember correctly. For example: http://www.prepchem.com/synthesis-of-diphenylmethanol/

[Edited on 17-6-2019 by DraconicAcid]

[Edited on 17-6-2019 by DraconicAcid]

Pumukli - 17-6-2019 at 01:37

With Fe/HCl I don't know.

With Sn/acetic acid or Zn/acetic acid it is reported. E.g. I tried to reduce benzyl with Zn/acetic acid in order to get benzyl-phenyl-ketone. It worked. The preparation would have been even better if I had used Sn powder, but I only had Zn. (According to the recipe Sn powder gives higher yield.)

In the old days distilling something "from Zn powder" was a standard way of reduction / deoxygenation. I have some faint memories of reducing ketones to alkanes by the above or similar (maybe acid involved) method. Clemensen reduction comes to mind, but it uses Zn amalgam.

Corrosive Joeseph - 17-6-2019 at 03:51

"The reduction of various substrates by dissolving metals in alcoholic and aqueous media is a very old procedure in synthetic organic chemistry. In addition to aldehydes, ketones, imines and other unsaturated nitrogen compounds, many other functional groups are reduced under these conditions.
Historically, the most common reduction conditions were Na in ethanol, and the reductions were carried out by adding the metal to a solution of the substrate in alcohol and the reaction mixture was heated at reflux for varying periods of time.
Other reduction systems included Na-Hg amalgam in water or alcohols and, for easily reduced compounds such as aldehydes and aromatic ketones, Zn-NaOH or Fe-acetic acid have been used. [Ref.4]"

Reduction of C=X to CHXH by Dissolving Metals and Related Methods -
https://www.sciencemadness.org/whisper/files.php?pid=301040&...

/CJ

karlos³ - 17-6-2019 at 05:23

You can use a nickel(II) salt in ammonia solution and add zinc powder to it(three portions) while the substrate is already added, that is some sort of pseudo Urushibara and gives a high yield for everything I have tried it on.

Corrosive Joeseph - 17-6-2019 at 06:04

Quote: Originally posted by karlos³

You can use a nickel(II) salt in ammonia solution and add zinc powder to it(three portions) while the substrate is already added, that is some sort of pseudo Urushibara and gives a high yield for everything I have tried it on.

Oh yeah, I had forgotten about that......

That reduction system used on benzaldehyde produced much benzyl alcohol and quite a surprise, benzylamine was the expected product.

Because the same system on cyclohexylamine gave high yields of amine.
https://www.sciencemadness.org/whisper/viewthread.php?tid=20...

But upon reading the fucking patent again, it all made sense (facepalm) -
https://chemistry.mdma.ch/hiveboard/chemistrydiscourse/00027...

Everything so far would indicate aldehydes yield alcohols and ketones give amines, but this shit is voodoo, so that is open to change at any time.

/CJ

DraconicAcid - 17-6-2019 at 11:10

Anyone know if aluminum would work without mercury? It should be a great reducing agent, less likely to go rusty and unusable than iron powder, but I never see it in the literature.

I'm specifically looking to reduce aromatic nitro groups to amines at the moment.

[Edited on 17-6-2019 by DraconicAcid]

karlos³ - 17-6-2019 at 11:16

You can actually use the Ni/Zn couple for these things too.
Here is also somewhere posted about a nickel aluminium couple(by clearly_not_atara I think) which I believe can also reduce aromatic nitros to the amine.

DraconicAcid - 17-6-2019 at 11:50

Quote: Originally posted by karlos³

You can actually use the Ni/Zn couple for these things too.
Here is also somewhere posted about a nickel aluminium couple(by clearly_not_atara I think) which I believe can also reduce aromatic nitros to the amine.

For the Ni/Zn bit, I've read that zinc is an unreliable reductant for aromatic nitros because it sometimes stops at the hydroxylamine (presumably because it forms a com-plex with it). Since iron doesn't form amino complexes very readily, it seems to be the favoured reductant, but aluminum also doesn't coordinate with ammonia.

I've found a thread by TheCopperMan, based on woelen's work....I'll be reading a while.

[Edited on 17-6-2019 by DraconicAcid]

Corrosive Joeseph - 17-6-2019 at 17:42

Quote: Originally posted by DraconicAcid

I'm specifically looking to reduce aromatic nitro groups to amines at the moment.

Ah......... Er........ What has that got to do with 'reduction of carbonyl without NaBH4 or LAH'........?

"The most popular reducing agent for conversion of aromatic nitro compounds to amines is iron [Ref.166]. It is cheap and gives good to excellent yields [Ref.165, 582]. The reductions are usually carried out in aqueous or aqueous alcoholic media and require only catalytic amounts of acids (acetic, hydrochloric) or salts such as sodium chloride, ferrous sulfate or, better still, ferric chloride [Ref.765]. Thus the reductions are run essentially in neutral media.
The rates of the reductions and sometimes even the yields can be increased by using iron in the form of small particles [Ref.765]. Iron is also suitable for reduction of complex nitro derivatives since it does not attack many functional groups"

Fe-H2O-FeCl3 gives 45.6-100% yields and Zn and HCl reported at 55%

Hudlicky - Reductions in Organic Chemistry Pages 72-74
https://ia800203.us.archive.org/30/items/Reductions_in_Organ...

It is well known since 1925 that zinc and ammonium chloride stop at the hydroxylamine -
http://www.orgsyn.org/demo.aspx?prep=CV1P0445

And if I remember correctly, atara's aluminum-NiCl2 paper used MASSIVE amounts of reductants to achieve it's end.......... Where is it.........?
Aha, nitrobenzene to aniline in 90% yields.
https://www.sciencemadness.org/whisper/viewthread.php?tid=65...

But wait.......... There's more.........!!

"U-Ni-B is effectively employed in catalytic reductions for which the presence of alkali is favorable; whereas U-Ni-A is appropriate for those reductions where the presence of alkali interferes. For example, a trace amount of alkali favors the reduction of ketones, aldehydes, nitriles, and oximes, for which the use of U-Ni-B is desirable. On the other hand, the reduction of aromatic nitro compounds is hindered by the presence of alkali and U-Ni-A can conveniently be used in this case."

https://www.erowid.org/archive/rhodium/chemistry/urushibara....

And people might as well forget about CopperMan's aluminum foil and CuSO4, it was completely unreliable, unreproducable in fact, although that unconjugated nitro molecule is a complete bitch to reduce in one go and has tortured chemists for over 100 years now. Not one member could repeat the original work. It probably works very well on something as easily reduced as the aromatic nitro group, but personally, I wouldn't even bother. Maybe someone might prove me wrong.

Back OT, there is a ton of references in my links for the reduction of carbonyl without NaBH4 or LAH......... That'll do for now.

/CJ

DraconicAcid - 17-6-2019 at 18:18

Quote: Originally posted by Corrosive Joeseph

Quote: Originally posted by DraconicAcid

I'm specifically looking to reduce aromatic nitro groups to amines at the moment.

Ah......... Er........ What has that got to do with 'reduction of carbonyl without NaBH4 or LAH'........?

Almost nothing but a "while we're discussing alternative reducing agents" aside. Thanks for your input.

Corrosive Joeseph - 17-6-2019 at 19:00

Quote: Originally posted by DraconicAcid

Almost nothing but a "while we're discussing alternative reducing agents" aside. Thanks for your input.

Apologies for my 'flippant quip' there, but seeing as 'alternative reducing agents' are a perverse fetish of mine, I have some more information for ya........

"The reduction of nitroaromatics to anilines with iron powder is carried out in a mixture of methanol and concentrated Hydrochloric Acid (eq 3). In the absence of methanol, only partial reduction is observed. [Ref.4]
Fe, MeOH and HCl in 89% yields.

The reduction of optically active nitroalkanes to active amines is accomplished with iron in Acetic Acid. The reaction proceeds with ≥82% optical purity. Other reducing agents, such as Lithium Aluminum Hydride, gave a completely racemic mixture of amines. [Ref.5]"
https://sci-hub.se/10.1002/047084289X.ri051

Just found the classic carbonyl reduction with Fe-AcOH again -
http://www.orgsyn.org/Content/pdfs/procedures/cv1p0304.pdf

And regarding zinc and carbonyls...........

"Reduction of Carbonyl Groups - Zinc reduces ketones to either alcohols or to a methylene unit, depending on the reaction conditions and the nature of the substrate. For example, conjugation is required if reduction to a hydroxy group is desired.
The reduction of aryl ketones provides benzylic alcohols (eq 4) [Ref.15] and a-diketones can be converted selectively to a-hydroxy ketones
(eq 5) [Ref.16].
The reduction of the carbonyl group of nonconjugated ketones to a methylene unit with zinc and hydrochloric acid in organic solvents such as ether, acetic anhydride, or benzene–ethanol proceeds in satisfactory yields with a wide range of ketones
(Clemmensen reaction) (eqs 6–8) [Ref.17].
The Clemmensen reduction of aromatic a-hydroxy ketones gives conjugated alkenes [Ref.18].
Mixed pinacol products have been prepared by using Zn(Cu) as the reducing agent (eq 13).
https://sci-hub.se/10.1002/047084289X.rz001.pub3

/CJ

Corrosive Joeseph - 17-6-2019 at 19:02

Taken from Weygand and Hilgetag (1972)

"Aliphatic aldehydes can, in general, be very smoothly reduced to primary alcohols by non-noble metals. Zinc powder or iron powder in glacial acetic acid can be used for this purpose, although the acetates of the resulting alcohols are often formed in a side reaction. Hill and Nason [Ref. 302] studied the effect of various metals in combination with glacial acetic acid in the reduction of cinnamaldehyde. They found that use of iron repressed the formation of glycol that occurred as side reaction and also protected the ethylenic bond. A detailed
prescription for preparation of heptyl alcohol [Ref. 303] is based on the work of these authors."

This next procedure will take cinnamaldehyde to cinnamyl alcohol, and is based on the work of Hill and Nason -
[Ref. 303] n-Heptyl Alcohol (1924) http://www.orgsyn.org/demo.aspx?prep=CV1P0304
Already linked in the post above.

Taken from the link -
"Ruhoff and Reid observed that the addition of a solution of nickel chloride hexahydrate will cause the reduction of heptaldehyde to start at once and will greatly increase the rate of reduction.
It is suggested, therefore, that, with a run of the size described above, a solution of 20 g. of nickel chloride hexahydrate in 50 cc. of water be added to the reaction mixture immediately after the addition of the aldehyde. If this is done, the reduction starts at once and is complete in two hours instead of the usual six to seven hours."

And finally, the Hill and Nason paper "The Utilization of Cassia Oil for the Synthesis of Cinnamyl Alcohol" (1924)
https://sci-hub.se/10.1021/ja01675a014

"The Effect of Metallic Salts on the Reduction -
Attempts were made to catalyze the reduction by means of metallic salts. It is well known that iron does not form couples with other metals. The effect of a couple is often produced when metallic salt solutions are added to an iron reduction mixture. Two experiments of this nature, made with copper and nickel sulfate solutions, gave rather surprising results. In both experiments, 100 cc. of a 10% solution of the sulfate was added gradually to a reduction mixture containing 65 g. of iron, 300 cc. of 60% acetic acid and 35 g. of
cinnamyl diacetate. The temperature, time and manipulation were those previously shown to give optimum results.
The addition of cupric sulfate increased the amount of unchanged aldehyde to 14%, while nickel sulfate appeared to make the reduction more complete. An examination in each case of the crude alcohol revealed the interesting facts that cupric sulfate merely decreased the amount of reduction, while nickel sulfate produced considerable phenylpropyl alcohol, with no unchanged aldehyde."

/CJ

Assured Fish - 20-6-2019 at 15:11

@JoseTineo I realize this doesn't exactly answer the question you asked but the conditions are still comparatively mild and i think you should look into it.
https://en.wikipedia.org/wiki/Bouveault%E2%80%93Blanc_reduct...

chemplayer... - 2-7-2019 at 23:22

Depends what you want to reduce it to. Wolff-Kishner using hydrazine (which can be prepared from OTC materials) will take the ketone down to the alkane.

clearly_not_atara - 3-7-2019 at 09:26

Anhydrous Chromium (II) salts are soluble in some aprotic solvents and react with electrophiles. They have been occasionally applied to nitro and ketone reductions but the literature is very thin. They are particularly known for forming Takai reagents by rxn with geminal dibromides/diioidides.

mackolol - 4-7-2019 at 07:24

Thiourea dioxide is able to reduce ketone group. There was even chinese patent written about, but unfortunately i lost it :/

Attachment: reduction of nitro compounds with TUDO.pdf (535kB)
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