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All 3 posts Subject: Possible new pathway to dipipanone or methadone Please login to post Down

wolff_kishner
(Newbee)
11-13-04 17:41
No 541392
      Possible new pathway to dipipanone or methadone

SWIM has dreamt up a possible new pathway toward dipipanone and/or methadone using two grignard reactions instead of one like in the original synthesis method for methadone on Rhodium's site https://www.rhodium.ws/chemistry/methadone.html. SWIM's synthesis involves no nitriles or cyanides, and SWIM has a hunch that no rearrangement to isomethadone or isodipipanone will occur (SWIM is not sure of this, however)

Note: Dipipanone has the same structure as methadone, except there is a piperidino group on the 6 carbon instead of a dimethylamino group.

Names may not be 100% IUPAC compliant, but they describe the molecule well enough, IMO.

Step 1: Acetone is halogenated to from haloacetone

Step 2: Haloacetone is reductively aminated with dimethylamine (methadone) or piperidine (dipipanone) to form 1-chloro-2-dialkylaminopropane.

Step 3: The 1-chloro-2-dialkylaminopropane is reacted with magnesium in ether to form the Grignard reagent.

Step 4: The Grignard reagent is reacted with benzophenone to make 1,1-diphenyl-3-dialkylamino-butanol.

Step 5: 1,1-diphenyl-3-dialkylamino-butanol is chlorinated with a suitable agent (such as thionyl or oxalyl chloride) to form 1,1-diphenyl-1-chloro-3-dialkylamino-butane.

Step 6: 1,1-diphenyl-1-chloro-3-dialkylamino-butane is reacted with magnesium in ether to form the Grignard reagent.

Step 7: The Grignard reagent is reacted with propanal to form 3-hydroxy-4,4-diphenyl-6-dialkylamino-heptane.

Step 8: 3-hydroxy-4,4-diphenyl-6-dialkylamino-heptane is oxidized with dichromate (or other suitable oxidizing agent) to yield dipipanone or methadone.

There may be a possibility of either one or both of the grignard reagents not working because of steric hinderance of benzophenone (for the first Grignard) or 1,1-diphenyl-1-chloro-3-dialkylamino-butane (for the second Grignard).

Also, will the Grignard induce any kind of rearrangement that will result in some isomethadone or isodipipanone?

SWIM tends to be blind to practical problems with theoretically sound syntheses, so SWIM thought he would post this on the Hive to find out if this synth has a chance of working with decent yields. SWIM thanks you in advance for your help.

Osmium
(Stoni's sexual toy)
11-13-04 21:29
No 541423
User Picture       > find out if this synth has a chance of...

> find out if this synth has a chance of working with decent yields

No eight step synth has decent yields.

> Haloacetone is reductively aminated with dimethylamine (methadone) or piperidine
> (dipipanone) to form 1-chloro-2-dialkylaminopropane.

Does the amine know that it is expected to react with the carbonyl instead of the halogen?

BUSH/CHENEY 2004! After all, it ain't my country!
www.american-buddha.com/addict.war.1.htm

wolff_kishner
(Newbee)
11-14-04 03:22
No 541481
      My mistake

Does the amine know that it is expected to react with the carbonyl instead of the halogen?

It doesn't. blush SWIM's mistake. Thanks for pointing that out.

I guess you would have to basify the haloacetone to yield a ketoalcohol, then use thionyl or oxalyl chloride to restore the halogen.

You're right that this is a cumbersome synthesis. SWIM is not actually planning to use this to synthesize narcotics. However, SWIM would still like to know whether steric hinderance would inhibit any of the Grignard reactions, because SWIM has not quite understood to what extent sterics have on hindering Grignard reactions. Different sources have yielded different answers.

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	All 3 posts		Subject: Possible new pathway to dipipanone or methadone		Please login to post		Down


		wolff_kishner (Newbee) 11-13-04 17:41 No 541392				Possible new pathway to dipipanone or methadone
						SWIM has dreamt up a possible new pathway toward dipipanone and/or methadone using two grignard reactions instead of one like in the original synthesis method for methadone on Rhodium's site https://www.rhodium.ws/chemistry/methadone.html. SWIM's synthesis involves no nitriles or cyanides, and SWIM has a hunch that no rearrangement to isomethadone or isodipipanone will occur (SWIM is not sure of this, however) Note: Dipipanone has the same structure as methadone, except there is a piperidino group on the 6 carbon instead of a dimethylamino group. Names may not be 100% IUPAC compliant, but they describe the molecule well enough, IMO. Step 1: Acetone is halogenated to from haloacetone Step 2: Haloacetone is reductively aminated with dimethylamine (methadone) or piperidine (dipipanone) to form 1-chloro-2-dialkylaminopropane. Step 3: The 1-chloro-2-dialkylaminopropane is reacted with magnesium in ether to form the Grignard reagent. Step 4: The Grignard reagent is reacted with benzophenone to make 1,1-diphenyl-3-dialkylamino-butanol. Step 5: 1,1-diphenyl-3-dialkylamino-butanol is chlorinated with a suitable agent (such as thionyl or oxalyl chloride) to form 1,1-diphenyl-1-chloro-3-dialkylamino-butane. Step 6: 1,1-diphenyl-1-chloro-3-dialkylamino-butane is reacted with magnesium in ether to form the Grignard reagent. Step 7: The Grignard reagent is reacted with propanal to form 3-hydroxy-4,4-diphenyl-6-dialkylamino-heptane. Step 8: 3-hydroxy-4,4-diphenyl-6-dialkylamino-heptane is oxidized with dichromate (or other suitable oxidizing agent) to yield dipipanone or methadone. There may be a possibility of either one or both of the grignard reagents not working because of steric hinderance of benzophenone (for the first Grignard) or 1,1-diphenyl-1-chloro-3-dialkylamino-butane (for the second Grignard). Also, will the Grignard induce any kind of rearrangement that will result in some isomethadone or isodipipanone? SWIM tends to be blind to practical problems with theoretically sound syntheses, so SWIM thought he would post this on the Hive to find out if this synth has a chance of working with decent yields. SWIM thanks you in advance for your help.



		Osmium (Stoni's sexual toy) 11-13-04 21:29 No 541423				> find out if this synth has a chance of...
						> find out if this synth has a chance of working with decent yields No eight step synth has decent yields. > Haloacetone is reductively aminated with dimethylamine (methadone) or piperidine > (dipipanone) to form 1-chloro-2-dialkylaminopropane. Does the amine know that it is expected to react with the carbonyl instead of the halogen? BUSH/CHENEY 2004! After all, it ain't my country! www.american-buddha.com/addict.war.1.htm



		wolff_kishner (Newbee) 11-14-04 03:22 No 541481				My mistake
						Does the amine know that it is expected to react with the carbonyl instead of the halogen? It doesn't. SWIM's mistake. Thanks for pointing that out. I guess you would have to basify the haloacetone to yield a ketoalcohol, then use thionyl or oxalyl chloride to restore the halogen. You're right that this is a cumbersome synthesis. SWIM is not actually planning to use this to synthesize narcotics. However, SWIM would still like to know whether steric hinderance would inhibit any of the Grignard reactions, because SWIM has not quite understood to what extent sterics have on hindering Grignard reactions. Different sources have yielded different answers.

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