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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.

molecules

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 $\ce{C}$.

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 '15 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 '15 at 15:19
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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 C-X bond (x=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 off that could extend a carbon chain...

I can think of one. $\ce{CN-}$ (cyanide ion). Could you take it from here?

I am willing to give further hints if necessary :)

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  • $\begingroup$ so 1. react with KCN 2. react with conc. h2so4 to give a carboxylic acid 3. react with NH(Me)2 to give the product. Am I right in thinking that all these steps can happen with water as a solvent? $\endgroup$ – Goods Apr 15 '15 at 15:21
  • $\begingroup$ @goods That sounds good. Now, once you've isolated the carboxylic acid, you can react it 'neat' with NH(Me)2 and moelcular sieves. The moelcular sieves simply ensure a dry reaction and very high temperatures are needed (approx 160 deg. 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. $\endgroup$ – Ari Ben Canaan Apr 15 '15 at 15:34
  • $\begingroup$ 2. react with conc. h2so4 under aqueous conditions would hydrolyse it to give a carboxylic acid $\endgroup$ – Goods Apr 15 '15 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 '15 at 19:17
  • $\begingroup$ @jerepierre to do this i would react it with socl2 right? $\endgroup$ – Goods Apr 15 '15 at 19:23

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