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Suggest a synthetic route to amide C from the alkyl chloride B (reaction mechanisms are not required). Standard reagents and solvents may also be used.

N,N,3‐trimethylbutanamide from 1‐chloro‐2‐methylpropane

In this question immediate reaction is to make a grignard reagent with B by reacting it with magnesium and have it attack $\ce{COX(N(Me)2)}$ to form C.

I'm not sure how it would be possible to make $\ce{COX(N(Me)2)}$ from standard reagents.

Are there any obvious synthesis ideas I'm missing in making $\ce{COX(N(Me)2)}$ as surely if I started from $\ce{COXY}$ where $\ce{X}$ and $\ce{Y}$ are Leaving groups, I would end up with $\ce{CO(N(Me)2)2}$ on reaction with $\ce{NH(Me)2}$ which would give an alcohol as the end product, as the amine isn't a good leaving group?

Also would $\ce{COXY}$ i.e. $\ce{COCl2}$ even count as a standard reagent? I have no idea what that really entails.

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    $\begingroup$ COCl2 (phosgene) is a standard reagent, but you can't use it here because you won't be able to stop at a single addition of Grignard to phosgene. Making a Grignard is a good idea, but try adding it to a different one carbon electrophile that gives a carboxylic acid (or carboxylate). $\endgroup$
    – jerepierre
    Apr 15, 2015 at 15:12
  • $\begingroup$ I don't think it's necessary to start with a Grignard; it is not stipulated in the question? Correct me if I'm wrong. $\endgroup$
    – Ari Ben Canaan
    Apr 15, 2015 at 15:19
  • $\begingroup$ You can make dimethylcarbamic chloride (Me)2NC(O)Cl from DMF with thionyl chloride or just buy it, it is commercially available for quite cheap. Addition of your Grignard to it should be simple as you suggested. $\endgroup$
    – szentsas
    Feb 26, 2020 at 16:08

1 Answer 1

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Phosgene, $\ce{O=CCl2}$, is a potent toxin and in no way would I consider it a safe or even standard laboratory reagent (at least on an undergraduate level).

Allow me to lead you down the garden path of organic synthesis.

We have a haloalkane. What do we know about such compounds; they have a polarised $\ce{C-X}$ bond ($\ce{x}$ is a halogen) and are prone to nucleophilic attack/substitution. In this case, we have a nice primary, haloalkane, hence, any nucleophilic substitution is likely to be SN2.

Now, the target is an amide, but what do we note is different about the target versus the starting material (SM)? There's an extra carbon present (and yes there's no halogen).

Warning bells should be going off at this time. What nucleophilic, reagent do we know of that could extend a carbon chain? I can think of one: $\ce{CN-}$ (cyanide ion).
So, first react with $\ce{KCN}$, second react with conc. $\ce{H2SO4}$ to give a carboxylic acid, third react with $\ce{NH(Me)2}$ to give the product. Now, once you've isolated the carboxylic acid, you can react it 'neat' with $\ce{NH(Me)2}$ and molecular sieves. The molecular sieves simply ensure a dry reaction and very high temperatures are needed (approx $\pu{160 ^\circ C}$). You could convert the carboxylic acid to an acyl chloride and react the amine to ensure a very high yield and 'fast' albeit more 'vigorous' reaction; in this case any ordinary organic solvent should suffice.

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  • $\begingroup$ 2. react with conc. h2so4 under aqueous conditions would hydrolyse it to give a carboxylic acid $\endgroup$
    – Goods
    Apr 15, 2015 at 15:35
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    $\begingroup$ @goods This strategy is fine, but you definitely want to derivatize the carboxylic acid (acyl chloride would be best, but there are alternatives) before reacting with the amine. The acid/base reaction between the amine and carboxylic acid is so favorable that direct amide formation is difficult. $\endgroup$
    – jerepierre
    Apr 15, 2015 at 19:17
  • $\begingroup$ @jerepierre to do this i would react it with socl2 right? $\endgroup$
    – Goods
    Apr 15, 2015 at 19:23
  • $\begingroup$ @goods That's the most common way. $\endgroup$
    – jerepierre
    Apr 15, 2015 at 19:40

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