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Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: Babcock_Hall on June 24, 2020, 05:18:17 PM

Title: conversion of an acetal to an aldehyde in high yield
Post by: Babcock_Hall on June 24, 2020, 05:18:17 PM
I attempted to convert methyl 4,4-dimethoxybutanoate into its aldehyde using acid hydrolysis for subsequent chemical synthesis.  I followed the protocol in Drinan, Martin A. and Lash, Timothy D. Journal of Heterocyclic Chemistry, 31(1), 255-7; 1994.  https://doi.org/10.1002/jhet.5570310144.  This protocol was quite detailed in the volumes of solvents used in the extraction, and I tried to follow it very closely.  Nevertheless my recovery was lower than the published value (which I seem to recall was 87%).  I think that one reason my recovery was low (roughly 30%) is that the product is more volatile than I thought it was.  I lost some mass during 30 minutes of (semi)high vacuum.  I even noticed a slow loss of mass when I subsequently used a stream of nitrogen (I thought that I was removing DCM from the extraction after the hydrolysis, but now I think that most or all of the DCM was already gone).

Should I try a different protocol for hydrolysis of the acetal, or would it be better to try an entirely different approach?  One possibility is to start with the 4-hydroxy ester and oxidize it under mild conditions to the aldehyde.  I have found some oxidations leading to the same product via SciFinder, but I have not attempted to evaluate them.

One thing that I would do differently is to take an NMR right after the rotary evaporation.  Then I would use nitrogen and follow the loss of any remaining DCM by NMR.  Tedious perhaps, but better than losing product.
Title: Re: conversion of an acetal to an aldehyde in high yield
Post by: rolnor on June 26, 2020, 11:55:04 AM
I would repeat as you suggest, run nmr before applying vacuum or N2-stream.
Title: Re: conversion of an acetal to an aldehyde in high yield
Post by: blackcat on June 30, 2020, 03:37:30 PM
For the 87% recovery reported in the literature, what procedure did they use? You have some difficulty following that?
Title: Re: conversion of an acetal to an aldehyde in high yield
Post by: Babcock_Hall on June 30, 2020, 05:22:28 PM
Drinan and Lash reported an 87% yield.  Others also reported high yields (the document which I used to summarize these protocols resides on a different computer, but I will check it when I have the opportunity).  I chose Drinan and Lash because they provided more information on the volumes used in the extraction than the other authors did.  I took care to saturate with NaCl as the protocol directed and cannot say that I had any difficulty in following it.  The yield was, however, disappointing.
Title: Re: conversion of an acetal to an aldehyde in high yield
Post by: kriggy on August 06, 2020, 01:22:14 AM
That is not uncommon in chemistry to be honest. Usually, it takes few attempts to get to teh reported yields but you probably know that. I just think your product is volatile and you lost it during the drying.