[Coolster7]

I've been asked to synthesise this ferrocene based macrocycle (shown in picture below) starting from ferrocene and other available materials from Aldrich. I need to make sure molar equivalents are spot on with reagents.

Basically, I need to give a synthetic route starting from ferrocene to get to that compound in the picture.



Can anyone help please? 

[zsinger]

I'm not sure, however I would try to make this ring as electrophilic as possible BEFORE any attack, as you want the hetero-cycle, and not individual fragments scrambled on the molecule through a single bond.  Thats all I got!  We just add acetyl-chloride to ferrocene with AlCl3 and check whether we get the mono-substituted product.  Hope this helps.
         -Zack

[Archer]

I've been asked to synthesise this ferrocene based macrocycle (shown in picture below) starting from ferrocene and other available materials from Aldrich.

Are you familiar with retrosynthesis?

[Dan]

Coolster7, you must show you have attempted the question - this is a Forum Rule.

[Coolster7]

I'm not sure, however I would try to make this ring as electrophilic as possible BEFORE any attack, as you want the hetero-cycle, and not individual fragments scrambled on the molecule through a single bond.  Thats all I got!  We just add acetyl-chloride to ferrocene with AlCl3 and check whether we get the mono-substituted product.  Hope this helps.
         -Zack

Thanks, I'm going to use the Richman Atkins synthesis to attach the diamine to the substituted ferrocene. Although this involves using h2so4 to remove a tosylate from the central nitrogen, are any of the reactants particularly sensitive to this?

Also do you know anyway of promoting mono substitution of ferrocene?

Thanks again for your reply.

[kriggy]

I would do friedel crafts acylation with formyl chloride and then reacted that with the needed diamine  to get you shiff base which could be reduced to give you desired product.

Or you can react substitued ferrocene with 2-chloro-ethylamine and then do wiliamson ether synthesis with diethanolamine and in the end reduce the shiff base with NaBH4 (might do some demetalation of your compound, not sure) or H₂

Also do you know anyway of promoting mono substitution of ferrocene?

Thanks again for your reply.

If we are talking about Friedel Crafts acylation that it should only go into 1 substitution

[zsinger]

Im more of a try it chemist than a hardcore book knowledge chemist, however, I do know that I would proceed in the first mentioned method by Kriggy due to cash constraints.  Might need Lindlar's (RG) in the last hydrogenation step of the alternative suggested synthesis, which aint cheap I don't think……I'm pretty sure it is dangerous and this scientist (me) avoids it at all costs!

[Archer]

I would do friedel crafts acylation with formyl chloride

Friedel Crafts Acylation does not work with formyl chloride.

I have a couple of viable routes to this compound.

How about letting the OP try to do some of the research themselves and critique their suggestions rather than doing their assignment for them.

@ Coolster7, show us your retrosynthetic scheme and your forward synthesis and we will help you refine it if it is unlikely to work.

As you have been provided with misinformation, if you want to formylate an aromatic system then the Vilsmeier–Haack reaction is commonly used. The question is would this reaction work with ferrocene?

[kriggy]

Friedel Crafts Acylation does not work with formyl chloride.

Thanks for correction, didn´t know that.
Sry for missinformation

[Archer]

Im more of a try it chemist than a hardcore book knowledge chemist

When you are at step 7 of a 12 step total synthesis this approach often leads to bitter disappointment.

[zsinger]

Truth Archer,
But sometimes, bitter disappointment has taught me the best lessons about the art of chemical synthesis.  Sometimes, you have to learn what DOESN'T work, and then ask yourself why……No disrespect intended dude, but I'm not a novice lab chemist.

[Coolster7]

I would do friedel crafts acylation with formyl chloride

Friedel Crafts Acylation does not work with formyl chloride.

I have a couple of viable routes to this compound.

How about letting the OP try to do some of the research themselves and critique their suggestions rather than doing their assignment for them.

@ Coolster7, show us your retrosynthetic scheme and your forward synthesis and we will help you refine it if it is unlikely to work.

As you have been provided with misinformation, if you want to formylate an aromatic system then the Vilsmeier–Haack reaction is commonly used. The question is would this reaction work with ferrocene?

Thanks to everyone for their replies.

I have used ferrocene with acetyl chloride in 2 equiventls to generate the diacid chloride. I know I can react this with the diamine and reduce the product with something like LiAlH4 to get the macrocycle. The problem is generating the diamine.

So far my idea is to start with a modified diethyl ether (basically just with -OH and -Cl on either side. Which I then react with a tosylated amine. This gives me the basic back bone of the structure, the central nitrogen is tosylated and the chain I want either side is the ether product with OH on the end (after losing Cl-)

Then I need to get from here to the actual diamine (exchange the OH for NH2 without damaging the rest of the chain)

[spirochete]

would each ring be nucleophilic at carbon? Could you mix a diamine with formaldehyde to make an iminium that then gets attacked by the nucleophilic carbons on the ring?

Add: A mannich, reaction, obviously.

[Archer]

Truth Archer,
But sometimes, bitter disappointment has taught me the best lessons about the art of chemical synthesis.  Sometimes, you have to learn what DOESN'T work, and then ask yourself why.

This is true but a very experienced chemist once told me the adage

"Six months in the lab can save you an afternoon in the library"

[Archer]

I have used ferrocene with acetyl chloride in 2 equiventls to generate the diacid chloride.

So far my idea is to start with a modified diethyl ether (basically just with -OH and -Cl on either side. Which I then react with a tosylated amine. This gives me the basic back bone of the structure, the central nitrogen is tosylated and the chain I want either side is the ether product with OH on the end (after losing Cl-)

Then I need to get from here to the actual diamine (exchange the OH for NH2 without damaging the rest of the chain)
 

Could you draw what you are proposing and upload it rather than putting it into text, this makes it much easier to follow.