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Offline acvkrs

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NaBH4 Reduction
« on: February 22, 2014, 01:25:59 PM »
I have studied NaBH4(Sodiumborohydride) as mild reducting agent that can reduce aldehydes and ketones (acid chlorides rarely)only. but in the real time laboratory, we are using NaBH4 for reducting Carboxylic acid and ester groups also. How it is possible? need explanation please...

Offline TheUnassuming

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Re: NaBH4 Reduction
« Reply #1 on: February 22, 2014, 02:01:01 PM »
It can't "normally" reduce those functional groups using standard conditions.  In practice there are certain cases and conditions where it can.  So my question for you is what conditions are you using exactly and what is the carboxylic acid/ester attached to? 
When in doubt, avoid the Stille coupling.

Offline discodermolide

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Re: NaBH4 Reduction
« Reply #2 on: February 22, 2014, 02:08:44 PM »
Borohydride will not reduce a carboxylic acid. It will reduce esters of benzoic acid in methanol/THF at 55°C. I guess this would also be the case for other esters.
To reduce a carboxylic acid you need BH3.DMS at reflux.
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Offline acvkrs

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Re: NaBH4 Reduction
« Reply #3 on: February 22, 2014, 02:19:11 PM »
It can't "normally" reduce those functional groups using standard conditions.  In practice there are certain cases and conditions where it can.  So my question for you is what conditions are you using exactly and what is the carboxylic acid/ester attached to?

Actually we are synthesizing an anti-viral drug by name FAMCICLOVIR. One of the stages is the reduction of ester groups with sbh+water solution and methanol as solvent. following is the scheme for it
Ph-CH2-O-CH2-CH2-CH(COOC2H5)2 + NaBH4  :rarrow: Ph-CH2-O-CH2-CH2-CH(CH2OH)2

explain plz

Offline opsomath

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Re: NaBH4 Reduction
« Reply #4 on: February 22, 2014, 02:42:36 PM »
In my limited experience beginning organic classes greatly overstate the selectivity of NaBH4. It doesn't reduce esters...unless you heat it up too much, or it's a particularly good leaving group on the ester, or the moon is in the right phase. It's enough that I wonder sometimes if there's a trace-transition-metal catalyst effect, since you can definitely use the same compound with Ni(II) cat. to reduce nitro groups.

Offline TheUnassuming

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Re: NaBH4 Reduction
« Reply #5 on: February 22, 2014, 05:25:43 PM »
@acvkrs: Are you using Ph or a guanine?  Pretty cool that it does the reduction, I wouldn't have guessed BH4 would knock down an alkyl-ester like that! 

@opsomath: haha, sophmore o-chem is full of wonderful things that get glossed over for the sake of brevity.  On the metal topic there are definitely a few literature precedents for using various metals in combination with BH4 to reduce "untraditional" moieties like esters.  Right to wonder if contaminant metals might be important to these reactions proceeding.

@Disco: True, you can't reduce a carboxylic acid with just BH4.  However with a few interesting other reactants in the mix you can... although I will concede its not a true hydride reduction as BH4 isn't the species that does the reduction :P.
When in doubt, avoid the Stille coupling.

Offline acvkrs

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Re: NaBH4 Reduction
« Reply #6 on: February 23, 2014, 09:05:30 AM »
That is the confusion that i've been facing for weeks. my educational knowledge says that sbh doesn't reduce carboxylic esters and acids. But my Sr. chemists showing me practically that sbh does so. May be they(my Sr. chemists) are assuming the path of the reaction in wrong way. but the wonder is that we are getting the final product(Famciclovir) at the end of the synthesis.

Offline discodermolide

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Re: NaBH4 Reduction
« Reply #7 on: February 23, 2014, 09:42:09 AM »
Borohydride in the presence of a mineral acid will produce borane which should reduce an acid and will certainly reduce esters.
As I said borohydride will reduce esters of benzoic acid at 55°C in methanol/THF. I have a procedure for doing that on >250Kg scale.
It will also reduce other aromatic esters under similar conditions.
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Offline acvkrs

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Re: NaBH4 Reduction
« Reply #8 on: February 23, 2014, 11:22:03 AM »
But we are not using any mineral acids in our reaction.
First we charge SM in to flask, then add 3V of t-buOH & then add NaBH4. To the above RM, add sbh solution very slowly(to avoid bumping) at 10-20 deg C. in 3-4 hours. that's all.

Offline opsomath

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Re: NaBH4 Reduction
« Reply #9 on: February 23, 2014, 07:50:22 PM »
Traces of acid in the tert-butyl alcohol?

Offline acvkrs

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Re: NaBH4 Reduction
« Reply #10 on: February 24, 2014, 09:58:46 AM »
No. No traces of mineral acids at all. Is there any chance of acid reduction by one of the bye product.? I mean, when nabh4 dissolves in methanol, it generates bh3 right? That bh3 might reduce the acid i think.any chance in this way??

Offline discodermolide

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Re: NaBH4 Reduction
« Reply #11 on: February 24, 2014, 12:51:17 PM »
No, NaBH4 dissolved in methanol does not produce BH3.
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Offline acvkrs

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Re: NaBH4 Reduction
« Reply #12 on: February 24, 2014, 10:52:24 PM »
Oh! Ok. So finally, nabh4 doesn't reduce acids at all. Right?

Offline discodermolide

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Re: NaBH4 Reduction
« Reply #13 on: February 25, 2014, 01:18:18 AM »
Sodium borohydride will not reduce a carboxylic acid.
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Offline Chymst

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Re: NaBH4 Reduction
« Reply #14 on: March 01, 2014, 03:10:12 PM »
You might find this interesting
Facile Reduction of Carboxylic Acids, Esters, Acid Chlorides, Amides and Nitriles to Alcohols or Amines Using NaBH4/BF3·Et2O
Bull. Korean Chem. Soc. 2004, Vol. 25, No. 3 407

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