[mscussel]

Hello, I need to get a hold of four methyl indan isomers for reference purposes. This includes 1-methyl, 2-methyl, 4-methyl, and 5-methyl indan. As far as I have found, these compounds are only available through a custom synthesis ($7K per compound).

I want to put my education/experience to good use and save my company a few $ and synthesize them myself. I'd also like to prevent burning down/destroying property where I work in the process, too.

I had a few different ideas..first, to synthesize 1- and 2- methyl indan by adding methane to the double-bond of indene. The methyl group could add to either position of the double bond on the 5-membered ring of indene, and the double-bond would be reduced, which would in turn give 1- and 2- methyl indan.

Then I thought perhaps there was a way to make 4- and 5-methyl indan starting with toluene and adding propane in a cyclization reaction to either the meta- and ortho- positions, or meta- and para- positions to give 4- and 5- methyl indan.

I'm not confident either of these pathways are possible (targeting the double bond of the 5-membered ring, adding propane in a cyclization reaction...both seem very unlikely)
======================================================
Finally, I found two articles that could help:

Cyclization of a o-(3-butenyl)bromobenzene via the Aryllithium deriviative, Ross, Koppanh, Bartak, Woolsey, J. Am. Chem. Soc, 1985, 6742-6743.
LINK http://pubs.acs.org/doi/abs/10.1021/ja00309a071
This outlines a specific path where i could possibly end up with 1-methyl indan.

More importantly,
Practical Procedures for the Perparation of N-tert-Butyldimethylsilylhydrozones and Their Use in Modified Wolff-Kishner Reductions and in the Synthesis of Vinyl Halides and gem-Dihalides, Furrow, Myers, J. Am. Chem. Soc., 2004, 126, 5436-5445
LINK http://pubs.acs.org/doi/abs/10.1021/ja049694s

Now the second article outlines how to eliminate a carbonyl group under mild reactions. Yet, this still involves the use of anhydrous hydrazine (scares me). Since the isomers I need are readily available with a carbonyl group (example 4-methyl-1-indanone), i could purchase the 4 isomers I need, then run a modified Wolff-Kishner reduction (outlined in the second paper) to end up with the hydrocarbons I need.

How difficult would this be? Can anyone offer any advice on the reduction reactions? I'd been years since my undergrad and I've been in the field of analytical chemistry for some time. I would just need some advice/reassurance to get started. I need to be aware of any potential dangers, and would like to know that it's going to work (obviously)!

Is there anyone who might be able to help? Let me know if there are any questions.

Thanks in advance!

[rolnor]

I have made a indanone through cyclization of phenylpropanoic acid using heat and polyphosphoric acid. One way to  reduce the carbonyloxygen would be to convert it to a thio-carbonyl and then desulphurize it with raney-nickel. I have found that indanones can be a little tricky, they dont always behave as other ketones. Phenylpropanoic acids are easy to make from the benzaldehyde and a wittig reagent, then hydrogenation. If the wittig reagent is benzyloxycarbonylmethylenetriphenylphosphorane the benzylester is also cleaved during the hydrogenation-step so you get the free phenylpropanoic acid direct. Another way to reduce the indanone would be to reduce it to the alcohol, eliminate to the alkene with acid and heat(p-TSA and refluxing xylene), then hydrogenation.

[orgopete]

When I was in industry, I had written on my hood, "Stick to what you know works". For all I know, $7K is cheap. I'd look up past syntheses. If you foresee these successful syntheses have are outdated, then try something new. Otherwise, you might want to stick to what has been reported. If you have a couple of failures, that $7K can creep up on you faster than you think.

[mscussel]

Thanks for the reply rolnor!

I have made a indanone through cyclization of phenylpropanoic acid using heat and polyphosphoric acid. One way to  reduce the carbonyloxygen would be to convert it to a thio-carbonyl and then desulphurize it with raney-nickel. I have found that indanones can be a little tricky, they dont always behave as other ketones. 

Do you think the thio/desulphurization over raney nickel would work on an indanone? What about raney nickel...I read it was pyrophoric. What type of precautions do you take to ensure safety?

Phenylpropanoic acids are easy to make from the benzaldehyde and a wittig reagent, then hydrogenation. If the wittig reagent is benzyloxycarbonylmethylenetriphenylphosphorane the benzylester is also cleaved during the hydrogenation-step so you get the free phenylpropanoic acid direct.

This applies if I were to form the indane in my own ring-forming reaction - then I wouldn't need to reduce an indanone, correct? Do you have a reference for this reaction?

Another way to reduce the indanone would be to reduce it to the alcohol, eliminate to the alkene with acid and heat(p-TSA and refluxing xylene), then hydrogenation.

Do you think this might be more laborious than the thio/desulphurization over raney nickel? Or might that reaction be more likely to produce better yield?

Sorry to hit you with more questions... I appreciate any more info you can give!

-Mike

 

[rolnor]

To maka a thioindanone from a indanone, with Lawesons reagent or phosphoruspentasulfide, that reaction I have not made. Yes raneynickel is pyrophoric but not when it is wet, it is stored under water.

From phenylpropionic acids you make the indanone, friedelcrafts reaction, you will have to reduce the indanone in this case also. No I dont have reference, sorry.

I think the reduction to the alcohol, elimination and hydrogenation is more likely to work then the sulphuration-desulphuration.
Have you got access to CAS-online, Scifinder etc.?

[critzz]

Hey, I put the suggestions of rolnor in a reaction scheme and added some own suggestions.
I would also go for the reduction/hydrogenation path.



You could indeed also make the starting acrylic acid yourself with a Wittig reaction, but I think its cheap enough to buy and it saves a step.

I would definately try to make these compounds myself because I like to synthesize stuff, but I don't know if its profitable in the end.

[rolnor]

Thank you critzz, I gave you a "Molesnack". The reaction with methyllitium I was thinking about, nice that you included it.

[critzz]

Woo tasty, a mole snack, haha. I gave you one as well. 

[kriggy]

You could save two steps by reducing the ketone directly into alkane by kishner-wolf for example
https://en.wikipedia.org/wiki/Wolff%E2%80%93Kishner_reduction