[sanderol]

Does anyone have any suggestions for the synthesis of the following benzocycloheptene. I would prefer the unsaturated one, although the other one would also be ok.

I keep on running into substitutions problems of the second substituent, since it will end up at the wrong place.

Any suggestion is welcome.

[nj_bartel]

from?

[sanderol]

whatever you may think of which is commercially available.

[aldoxime_amine]

alpha-bromo Tetralone + Tiffeneau Demjanov rearrangement

(Not a very commonly available compound, but it is available for $ 600 per gram in case you are interested.. )

[sjb]

alpha-bromo Tetralone + Tiffeneau Demjanov rearrangement

(Not a very commonly available compound, but it is available for $ 600 per gram in case you are interested.. )

Would that give the right isomer? I'd've thought the rearrangement would take the carbonyl away from the ring?

Long winded way aniline -> acetanilide -> friedel crafts glutaric anhydride in (separate from the p-isomer), protect the carbonyl, stick the other carbonyl on the ring in a second F/C, reduce the carbonyl, deprotect the amine, Sandmeyer the bromine and deprotect the carbonyl...?

[aldoxime_amine]

Would that give the right isomer? I'd've thought the rearrangement would take the carbonyl away from the ring?

There is only one ring methylene group which can migrate (see attached figure).

Long winded way aniline -> acetanilide -> friedel crafts glutaric anhydride in (separate from the p-isomer), protect the carbonyl, stick the other carbonyl on the ring in a second F/C, reduce the carbonyl, deprotect the amine, Sandmeyer the bromine and deprotect the carbonyl...?

Why not start of with bromobenzene itself? It will save the step of protecting/deprotecting the amine and the sandmeyer part...

[sjb]

Would that give the right isomer? I'd've thought the rearrangement would take the carbonyl away from the ring?

There is only one ring methylene group which can migrate (see attached figure).

Long winded way aniline -> acetanilide -> friedel crafts glutaric anhydride in (separate from the p-isomer), protect the carbonyl, stick the other carbonyl on the ring in a second F/C, reduce the carbonyl, deprotect the amine, Sandmeyer the bromine and deprotect the carbonyl...?

Why not start of with bromobenzene itself? It will save the step of protecting/deprotecting the amine and the sandmeyer part...

Ahh, I thought the T/D was more like the Beckmann, in which I think I've seen mixtures of amides formed from tetralones. As to why not bromobenzene to start with, I was concerned about the C-acylation happening at the C-Br too.

[alphahydroxy]

Would this be a reasonable route?

It's just off the top of my head, and it's not unlikely that there will be some huge, obvious, glaring error in there! Don't be shy to point it out and laugh at me!

[StarvinMarvin]

The only limitation of this route is that the starting material dihalobenzene in meta relations is either commercially unavailable or very expensive  - so in my view this route needs to be disqualified. Making such a compound also requires a lot of effort and couple additional steps.

[alphahydroxy]

The only limitation of this route is that the starting material dihalobenzene in meta relations is either commercially unavailable or very expensive  - so in my view this route needs to be disqualified. Making such a compound also requires a lot of effort and couple additional steps.

Do you mean the route I posted above?

The starting 3-bromoiodobenzene (CAS: 591-18-4) is available for just under £2/g from Sigma...

[StarvinMarvin]

I apologize then

Actually, I didn't check it out by myself. I just saw the structure and thought that making this one is a nice pickle itself:)

[orgopete]

Does anyone have any suggestions for the synthesis of the following benzocycloheptene. I would prefer the unsaturated one, although the other one would also be ok.

I keep on running into substitutions problems of the second substituent, since it will end up at the wrong place.

Any suggestion is welcome.

This is what I would try. Start with p-bromoacetanilide and do the glutaric anhydride double FC. Now you have the dione with two substitutents in the correct positions. The carbonyl groups will react at different rates. Use any sequence to differentiate them, hydrazone-Wolk-Kischner, NaBH4 (alcohol, then HI?), dithioketal reduce, etc. The reductions may be problematic or opportunistic. If the differentiation reduces the carbonyl ortho to the bromine, get rid of both. Then Sandmeyer to pdt.