Hi all, Excuse the cross post from another board. I realised Id get a more forthright response here after posting.
IMHO The Willgerodt in all of its unworldly manifestations belongs nowhere but the bowells of hell, and that dimisyl idea seems feasable in microgram theory, but Im not convinced through practice.
In saying that Im still quite interested in styrene as a starting block. Im short of time at the mo, and still getting my head around some of this, so please excuse any glaring mistruths. Ill keep it brief, but Ill post refs/pics experimental detail as I sort/find it. Consider this a short overview into which Ill insert refs as I go.
This is what Ive come to so far, and would appreciate any feedback from more knowledgeable dreamers.
What Im aiming at is routes from Cyclopropanated styrene derivatives. (Phenylcyclopropane being the intermediate when cinnamaldehyde is subjected to treatment with Hydrazine hydrate without base).
Now Styrene can be reacted with various reagents to form said cyclopropane.
1: Diazomethane derivatives catalysed by metal ligands.
2: Zinc-Copper and Dihalomethane.(Simmons-Smith reaction).
3: Iron Pyrorphins/insitu diazo complexs etc
And the list goes on. But nothing stands out as being either OTC or amature friendly.
On the other hand we have the option of another somewhat more indirect route which will also open up some more possibilities.
That being dichlorocarbene addition to styrene to form the geminal dihalide followed by dehalogenation and thermal/base catalysed isomerisation of the gem-dihalide to yield a mix of propenyl/ally benzene.
So first we would need to generate Dichlorocarbene.This can be done OTC with:
1: Carbon tetrachloride and magnesium under PTC or Ultrasound conditions.
2: Chloroform and Hydroxide under similar conditions.(Better)
This carbene will add to styrene insitu resulting in the formation of 1,1-dichloro-2-phenylcyclopropane.
Next to unselectively dehalogenate we can use.
1:Zinc dust in methanol/water
2:Dithionite in H20
3: Lithium or Sodium in Alcohol
4: Alkali metal in NH3 (for the SnBers)
This will yield straight Phenylcyclopropane. As mentioned above moderate temperature thermal rearangent of the cyclopropane yields our desires alkenes.
Alternatively base catalysed and you are vitually picking up at the end phase of the Wolf-kishner on cinnamaldehyde,yielding the same.
O.K so in a nutshell here we have :
1)Haloform + Base (PTC/ultrasound) -> Dihalocarbene + Styrene -> Dihalophenylcyclopropane.
2)Zinc/MeOH + Dihalophenylcyclopropane -> Phenylcyclopropane.
3) Phenylcycloppropane + Heat/base ->allyl/propenyl benzene(predominantly propenylbenzene).
Thats all good and well I suppose, but Im wondering if we can get a little bit trickier.
I.e Idea number :-
1) Hot Basic hydrolysis of the gem-dihalide should yield 2-Phenylpropionic acid sodium salt, which can then be halogenated, substituted to amide then Hoffman to amine.
2) React with Alkoxide to form an alkyl ester ,substitute to amide, Hoffman etc.
3) Dehalogenate as above, then react with PdCl2 to give a mix of phenylacetone/propiophenone.
4)Oxidative isomerisation by other means (Hg salts etc) to give mixed ketones.
5) Selective reductive dehalogenation (Dithionite) and subsequent ring opening of the monohalide to the desired Haloalkane. (This one interest me the most obviously. And this is where most of the conflicting info is found.) Depending on slight variations in method, reports described conflict as to which carbon cleavage will take place at.
Tthings I need to look into further:
6) Hydrolysis of the dihalide to Cyclic ketone and what can be done .
7) Amination of the monohalide and what can be done.
Alkyl cyclopropanes. Cyclopropyl carboxylates. and the Dakin rearangement.
Thats it for now. Unless Im totally trippin ballz, you can see this could open up many possibilites.
Please discuss/ shoot me down in flames.
Again Ill post refs for each step, as they are located/fullfilled by the good folk who do such kind work.
IMHO The Willgerodt in all of its unworldly manifestations belongs nowhere but the bowells of hell, and that dimisyl idea seems feasable in microgram theory, but Im not convinced through practice.
In saying that Im still quite interested in styrene as a starting block. Im short of time at the mo, and still getting my head around some of this, so please excuse any glaring mistruths. Ill keep it brief, but Ill post refs/pics experimental detail as I sort/find it. Consider this a short overview into which Ill insert refs as I go.
This is what Ive come to so far, and would appreciate any feedback from more knowledgeable dreamers.
What Im aiming at is routes from Cyclopropanated styrene derivatives. (Phenylcyclopropane being the intermediate when cinnamaldehyde is subjected to treatment with Hydrazine hydrate without base).
Now Styrene can be reacted with various reagents to form said cyclopropane.
1: Diazomethane derivatives catalysed by metal ligands.
2: Zinc-Copper and Dihalomethane.(Simmons-Smith reaction).
3: Iron Pyrorphins/insitu diazo complexs etc
And the list goes on. But nothing stands out as being either OTC or amature friendly.
On the other hand we have the option of another somewhat more indirect route which will also open up some more possibilities.
That being dichlorocarbene addition to styrene to form the geminal dihalide followed by dehalogenation and thermal/base catalysed isomerisation of the gem-dihalide to yield a mix of propenyl/ally benzene.
So first we would need to generate Dichlorocarbene.This can be done OTC with:
1: Carbon tetrachloride and magnesium under PTC or Ultrasound conditions.
2: Chloroform and Hydroxide under similar conditions.(Better)
This carbene will add to styrene insitu resulting in the formation of 1,1-dichloro-2-phenylcyclopropane.
Next to unselectively dehalogenate we can use.
1:Zinc dust in methanol/water
2:Dithionite in H20
3: Lithium or Sodium in Alcohol
4: Alkali metal in NH3 (for the SnBers)
This will yield straight Phenylcyclopropane. As mentioned above moderate temperature thermal rearangent of the cyclopropane yields our desires alkenes.
Alternatively base catalysed and you are vitually picking up at the end phase of the Wolf-kishner on cinnamaldehyde,yielding the same.
O.K so in a nutshell here we have :
1)Haloform + Base (PTC/ultrasound) -> Dihalocarbene + Styrene -> Dihalophenylcyclopropane.
2)Zinc/MeOH + Dihalophenylcyclopropane -> Phenylcyclopropane.
3) Phenylcycloppropane + Heat/base ->allyl/propenyl benzene(predominantly propenylbenzene).
Thats all good and well I suppose, but Im wondering if we can get a little bit trickier.
I.e Idea number :-
1) Hot Basic hydrolysis of the gem-dihalide should yield 2-Phenylpropionic acid sodium salt, which can then be halogenated, substituted to amide then Hoffman to amine.
2) React with Alkoxide to form an alkyl ester ,substitute to amide, Hoffman etc.
3) Dehalogenate as above, then react with PdCl2 to give a mix of phenylacetone/propiophenone.
4)Oxidative isomerisation by other means (Hg salts etc) to give mixed ketones.
5) Selective reductive dehalogenation (Dithionite) and subsequent ring opening of the monohalide to the desired Haloalkane. (This one interest me the most obviously. And this is where most of the conflicting info is found.) Depending on slight variations in method, reports described conflict as to which carbon cleavage will take place at.
Tthings I need to look into further:
6) Hydrolysis of the dihalide to Cyclic ketone and what can be done .
7) Amination of the monohalide and what can be done.
Alkyl cyclopropanes. Cyclopropyl carboxylates. and the Dakin rearangement.
Thats it for now. Unless Im totally trippin ballz, you can see this could open up many possibilites.
Please discuss/ shoot me down in flames.
Again Ill post refs for each step, as they are located/fullfilled by the good folk who do such kind work.