[davy0488]

I have this synthesis project due in my organic chemistry class on Monday, any suggestions for a synthesis? Any reagents are acceptable as long as they are in the Sigma-aldrich catalog.  Thank you!

-Dave

[sjb]

Are any of the links at http://www.organic-chemistry.org/synthesis/heterocycles/butenolides.shtm any use?

Or perhaps http://dx.doi.org/10.1016/j.tet.2006.08.085 - Tetrahedron 2006, 62, 10688-10693 ?

Don't have easy access to the literature at present  so this is based on a quick google.

Do you actually have to carry this out?

S

[davy0488]

Unfortunately, each reaction in the synthesis needs to be in our textbook, and although one particular reaction of tosylates is in the textbook, the reagents are not.  Thank you for the links though, any ideas are helpful.

[agrobert]

Work from this

http://www.sigmaaldrich.com/catalog/search/ProductDetail/ALDRICH/176451

It is hard to help you because we don't know what reactions you can use.  I think your assignment being limited to book reactions is dumb but what can you do.  Nitriles are commonly introduced through the Sandmeyer reaction diazotonation of aniline and displacement with CN.

[macman104]

Heh, nice find Agrobert.  What about the double bond that they need?

I was actually thinking about this one and then a radical chloronation to the position next to the ester O.  Then FC the benzene?  The only thing I don't know is if the chloro group will end up there, or the double bond resonate to the other position.

[sjb]

Work from this

http://www.sigmaaldrich.com/catalog/search/ProductDetail/ALDRICH/176451

Could you do standard selenate -> selenoxide and elimination chemistry on this, I fear it may open up the lactone.

It is hard to help you because we don't know what reactions you can use. I think your assignment being limited to book reactions is dumb
but what can you do.

Well, if we can sneakily add a "... and magazines ..." (sic - i.e. journals, maybe that'll help) 

Davy0488, what book are you using? If the exact reactions need to be in your book, does that faint alarm bell ringing in my head suggest that the actual synthesis is there too? 

Nitriles are commonly introduced through the Sandmeyer reaction diazotonation of aniline and displacement with CN.

True, also dehydration of primary amides is another reasonably common "book example" in my experience.

Heh, nice find Agrobert.  What about the double bond that they need?

I was actually thinking about this one and then a radical chloronation to the position next to the ester O.  Then FC the benzene?  The only thing I don't know is if the chloro group will end up there, or the double bond resonate to the other position.

I'm not sure, I think both isomers are fairly stable and not 100% certain of the energy barrier between the two. Certainly Joule and Mills (4th, page 307) suggest alpha and beta angelica lactone interconvert via 2-hydroxy-5-methylfuran, if I'm reading the page right.

[davy0488]

This is the synthesis that I had originally proposed, does it look feasable? 
Also, my book is Organic Chemistry by Wade, and no the synthesis is not in the book.  I understand that its difficult to help out but your feedback is appreciated.  Any ideas are helpful. 

[agrobert]

We can work with this.  You need to be more specific on your reagents (include everything).  I wish you could displace Br with NaCN that easily.  I think for your assignment this is almost acceptable but lets talk about it.

[davy0488]

Well, first of all, the Br2 and hv in the first step should be replaced with NBS, and in terms of the NaCN, that is one possible way to synthesize a nitrile according to our textbook.  The only things I am concerned about is the possibility of side reactions or the possibility of selectivity issues.  If you can suggest better reagents for any step, please let me know.  This is just a rough synthesis. 

[macman104]

In the step with KOH, the KOH is probably going to change your ester in an acid.

And then in your grignard step it magically turns back into an ester...

[davy0488]

Is there any way that we can use another leaving group that will not be affected by the KOH? Or is there any weaker base that we can use which will accomplish what needs to be accomplished and not affect the ester?  Do you have any suggestions?

[macman104]

If you protect your carbonyl with the acetal before you change the Br to OH, that should be enough.  Acetals are stable in base.

[sjb]

I could be wrong, but I don't think you can protect the carbonyl of a carboxylic acid that way. In fact, I don't ever recall seeing any protection of that at all - do you have any literature references? It may be that your book says you can protect ketones and aldehydes that way..?

Similarly, does the book say aliphatic bromides can be transformed into nitriles in the way you have described? It might be that you can convert electron poor aryl bromides into nitriles this way via Meisenheimer intermediates but I don't see it happening in this system.

I don't think the geometry of the lactone would allow ring closure as you've suggested it.

All annoying points, I'm sorry, but this I guess is a limitation of the exercise if you have to use "book examples" and only these. Good ideas in practice, but probably less so in reality.