Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: AdiDex on February 13, 2015, 05:56:49 AM
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I'm Confused why we can't reduce Carboxylic Acid Directly to Alcohol ??
We Have to first convert it into ester than Ester is Catalytic Hydrogenated at high pressure in presence of H2 gas to form Alcohol .!!!
My second Doubt
"Which is better to use to reduce anything LiAlH4 or Pd-C / H2 ??" Eg. I have to reduce -NO2 to form -NH2 , Can we use LiAlH4 ??
And What is Difference Between reactivity of Pd , Pt , Rh , Ni , Ru , in catalytical Hydrogenation ??
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Im not sure about your 1st question but about the second..
It depends. LAH is probably easier to work with since it is a powder while H2 is gas and requires special setup. There is no easy answer on this question, it depends on many factors but generaly speaking, by using H2 you can reduce pretty much anything you want into anything you want, but you need to have the right conditions
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This is something of a tangent, but when one uses a less active reducing agent, ones has to use an ester with a decent leaving group, such as phenoxide ion.
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This is something of a tangent, but when one uses a less active reducing agent, ones has to use an ester with a decent leaving group, such as phenoxide ion.
Ohk thats ok if ester having leaving group such as phenoxide (PhO-) or methoxide (OCH3-) they are pretty much good leaving group than Hydroxide (OH-) .
But If you have ester having Higher Substituents like pentoxide (OC5H11-) they are bad Leaving group due to large +I effect .
So I can conclude that We can't replace OH by anything it should be either OMe or OPh ..!! Am i right ?? But as far i know catalytical hydrogenation occurs through radical Mechanism ..!! So I think leaving group ability nothing to do with Hydrogenation .!!!
Can anybody How It get Reduce to Alcohol ??
RCOOR' + H2 :rarrow: RCH2OH + R'OH
First A Pi bond is breaks Radical forms and 2 Hydrogen get inserted but what will happen next ?? Can It Break
Sigma bond ??
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Im not sure about your 1st question but about the second..
It depends. LAH is probably easier to work with since it is a powder while H2 is gas and requires special setup. There is no easy answer on this question, it depends on many factors but generally speaking, by using H2 you can reduce pretty much anything you want into anything you want, but you need to have the right conditions
Ok That means We can use both method to reduce .!! Thanks :)
By the way we can reduce Carboxylic acid to Alcohol by Using LAH but i didn't find anywhere where reduction of Carboxylic acid by Catalytical Hydrogenation can take place..!!
Can Anybody Help me on my another Doubt No one is replying :(
http://www.chemicalforums.com/index.php?topic=78907.0 (http://www.chemicalforums.com/index.php?topic=78907.0)
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This is something of a tangent, but when one uses a less active reducing agent, ones has to use an ester with a decent leaving group, such as phenoxide ion.
Ohk thats ok if ester having leaving group such as phenoxide (PhO-) or methoxide (OCH3-) they are pretty much good leaving group than Hydroxide (OH-) .
For groups whose structures are similar, one can use basicity to estimate leaving group ability. Which is more basic, methoxide or phenoxide?
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You can chemoselectively reduce carboxylic acids to alcohols (and amides to amines) with BH3, like this:
(https://www.chemicalforums.com/proxy.php?request=http%3A%2F%2Fwww.orgmech.co.uk%2FFiles%2FRedox-%2520Reduction-%2520Diborane%2520reduction%2520of%2520carboxylic%2520acids.gif&hash=0be1bfc0d73bdf821a1f09a31b854d43f787b8f6)
Your second question is absolutely impossible to get answered in a short way...
What reducing agent is better depends much on the situation: What functional group/s are you trying to reduce, which other groups are present on the molecule and you don't want them to get reduced...
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This is something of a tangent, but when one uses a less active reducing agent, ones has to use an ester with a decent leaving group, such as phenoxide ion.
Ohk thats ok if ester having leaving group such as phenoxide (PhO-) or methoxide (OCH3-) they are pretty much good leaving group than Hydroxide (OH-) .
For groups whose structures are similar, one can use basicity to estimate leaving group ability. Which is more basic, methoxide or phenoxide?
Methoxide is more basic , As in case of phenoxide the lone pair are in conjugation .
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There is a nice new method, but from esters, which are easy to prepare.
see Iron-Catalyzed Hydrogenation of Esters to Alcohols. (2014). Iron-Catalyzed Hydrogenation of Esters to Alcohols., 53(48), 13004–13006. doi:10.1002/anie.201407613
for the method
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Your second question is absolutely impossible to get answered in a short way...
What reducing agent is better depends much on the situation: What functional group/s are you trying to reduce, which other groups are present on the molecule and you don't want them to get reduced...
Ok So that means both have their own advantages . Can you prefer me any link or book where i can get the information about reducing properties of different reducing agents ??
and what about reactivity order of these metals ??
Pd , Pt , Rh , Ni , Ru
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There is a nice new method, but from esters, which are easy to prepare.
see Iron-Catalyzed Hydrogenation of Esters to Alcohols. (2014). Iron-Catalyzed Hydrogenation of Esters to Alcohols., 53(48), 13004–13006. doi:10.1002/anie.201407613
for the method
Thank you very much :)
But i have same question why we can't use Carboxylic acid ??
Why usually we have to convert carboxylic acid into ester first ??
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This is something of a tangent, but when one uses a less active reducing agent, ones has to use an ester with a decent leaving group, such as phenoxide ion.
Ohk thats ok if ester having leaving group such as phenoxide (PhO-) or methoxide (OCH3-) they are pretty much good leaving group than Hydroxide (OH-) .
For groups whose structures are similar, one can use basicity to estimate leaving group ability. Which is more basic, methoxide or phenoxide?
Methoxide is more basic , As in case of phenoxide the lone pair are in conjugation .
Yes, so phenoxide is the better leaving group.
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Babcock_Hall Brother , Listen ..!!!
As far as I know Catalytical Hydrogenation take place by radical mechanism , so Leaving group ability will not have so much influence on reaction . As in this is case Homogeneous cleavage take place , heterogeneous cleavage will not..!!!
So why we are concerning about leaving group ability ???
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http://www.chemicalforums.com/index.php?topic=78907.0 (http://www.chemicalforums.com/index.php?topic=78907.0)
Someone please help me on this topic .
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I believe catalytic hydrogenation doesn't actually take place by a radical mechanism but this is a different discussion.
In any case, the carboxyl group seems to display very different reactivity to ester groups and is pretty much in the bottom rung of reactivity against reducing agents including H2 and even LiAlH4, with the exception of BH3.
The metals used in catalytic hydrogenation actually occasionally display curiously different chemoselectivities for different reducible substrates, although there is a general list of reactivity against said substrates that applies. The list has carboxylic acids smack bang at the bottom with esters being pretty challenging substrates also. This would perhaps be to do with their poor capacities to dock to the metal surface - important in the hydrog process.
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Babcock_Hall Brother , Listen ..!!!
As far as I know Catalytical Hydrogenation take place by radical mechanism , so Leaving group ability will not have so much influence on reaction . As in this is case Homogeneous cleavage take place , heterogeneous cleavage will not..!!!
So why we are concerning about leaving group ability ???
I brought up leaving groups because having a good leaving group is sometimes important in reduction reactions, such as when using LiAH(O-tert-Bu)3. You may recall that I had said that this topic might be tangential. I stayed with this topic because you said something that was incorrect: "Ohk thats ok if ester having leaving group such as phenoxide (PhO-) or methoxide (OCH3-) they are pretty much good leaving group than Hydroxide (OH-) ." Also leaving group ability may help explain the reduction of acyl chlorides. Here is a quick overview: https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/crbacid2.htm
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I'm going to attempt to give an answer to these two questions. I am going to do so without looking up any literature, so if I am wrong, please give a citation.
Re: hydride reductions
I think this can be complicated. A good leaving group can also result in a more electron deficient carbon nucleus. I would argue it is reactivity of the carbon that leads to the result rather than leaving group ability. (If all reactions formed a tetrahedral intermediate, then decomposition of it by the best leaving group would be fastest. I don't think they form or reversibly form a tetrahedral intermediate.)
I would argue that reduction of an acid chloride by HAl(OtBu)3[-] is an example of a very weak hydride donor reacting with a very reactive carbonyl compound. The product is less reactive and unable to react further.
The reduction of an ester can be done with a borohydride, but this reduction is also influenced by the Lewis acidity of the metal. Thus, LiBH4 is more effective in reducing ester than NaBH4 because lithium is a better Lewis acid (one of the forum moderators pointed this out to me). The method referred to by Disco appears to be a complexed borohydride reduction (from the abstract of the paper at least).
If I continue with the same reasoning, then reduction of a RCOOH with a hydride will first form a RCOO(-) anion and H2. A carboxylate will resist addition of a hydride compared to an ester, anhydride, or acid chloride. When reductions can succeed, they must also provide a method to convert what might have been written as a O(-,-) leaving group into something better, for example with a O=BR2(-) or O=AlR2(-).
Re: catalytic hydrogenolysis
I don't know the answer to this question, but I am a lumper. My preference is to assume that a given pair of electrons will behave similarly as we may know or may find in other reactions. I don't know the proof of the Heck reaction mechanism, but I felt you may find it logical. I therefore assumed a catalytic reduction might work analogously. Even if I am wrong, it may still provide a useful example to explain the chemistry found, for example the formation of trans olefins during catalytic reductions.
You can probably find tables that show which catalysts can be used with different substrates. This is data that could be used to hypothesis a mechanism or mechanisms for the reductions. What properties of the catalysts can be predicted from other reactions? I don't know the answer to the question, but I acknowledge the question is a good question. It is still a very complicated question with a lot of variables.
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Orgopete,
You raise some good points. However, I have a question. Which do you think is rate-determining, the formation of the tetrahedral intermediate or its breakdown? The reason why I ask is that phenyl esters may be a little bit more active than alkyl esters in reductions with LiAl(OtBu)3H. Of course, even assuming that this is true, it might be explained either by greater electrophilicity of the carbon atom or greater leaving group ability of the phenoxide ion.
"Preparation of Boc-Amino-Acid or Peptide Aldehydes via Reduction of Corresponding Phenyl Esters" http://onlinelibrary.wiley.com/doi/10.1002/hlca.19940770117/abstract
The Reaction of Lithium Tri-t-butoxyaluminohydride with Phenolic Esters.
http://pubs.acs.org/doi/pdf/10.1021/jo01339a063
With respect to catalytic hydrogenations, it is interesting that when the substrate is an acid chloride, a poisoned catalyst may be used.