original synth/writeup by krz and potisgood respectively, enjoy (not two links, was unable 2 locate krzs post. either way, i suggest opening it cuz the replies have important info ^_^ the synth will still work but one step may be unnecessary, need someone 2 check 4 me bc im not a chemistry expert)
After about a month of fucking around with KrZ's ethyl nitrite wacker, I finally got it working. And it works damn good. Not only is this method less messy than the benzo wacker but it also has the following advantages:
1) No need for benzo. Ethyl nitrite can be made from sodium nitrite, which is not that hard to get. Plus, the sodium nitrite can be regenerated from the NO gas generated by the reaction.
2) The yield is better.
3) Less PdCl2 is needed.
Now that it's perfected, this method is probably the best method around for making ketone. Here's the method that I have developed:
The glassware setup is fairly complicated, but I'll describe it as best I can. There are two parts to it -- A reaction setup and an EtONO (ethyl nitrite) generator. The reaction setup consists of a round bottom flask and a condenser. There should also be some way to input gas between the flask and the condenser. The top of the condenser should have a vacuum outtake attached to it to vent of the toxic NO gas that is produced.
The EtONO generator consists of a flat bottomed flask (round bottom will work too) with a pressure equalized addition funnel on top. A column packed with anhydrous CaSO4 is attached to the top of the addition funnel, and a vacuum outtake adapter should be connected to the top of the column. This vacuum adapter is then connected to the gas inlet on the reaction setup. The vacuum outtake on the reaction setup is connected to a bubbling apparatus or simply out the window. Fuck, that was pretty complicated huh? Too bad I don't have a picture.
Here is a breakdown of the method:
1) Add 140 mL anhydrous EtOH to the round bottom flask of the reaction setup. Now dissolve 775 mg anhydrous CuCl2 and 200 mg PdCl2 in the EtOH. You will have to let it stir for about 30 minutes at 30C to dissolve the PdCl2. When you first put the two solids in the EtOH, it will be a muddy brown color, with particles of PdCl2 floating around. After the PdCl2 is completely dissolved, the solution will turn an orange-ish color.
2) While you wait for the catalyst to dissolve, prepare a solution of 65 g NaNO2 and 160 mL H2O. Pour this in the flat bottomed flask of the EtONO generator.
3) Make a solution of 50 mL H2O, 50 g H2SO4, and 46 g EtOH. You must add the H2SO4 to the water first; then let is cool down and add the EtOH. Pour this solution into the addition funnel on the EtONO generator.
4) Once the PdCl2 is dissolved, run ice water through the condenser and begin dripping the contents of the addition funnel into the NaNO2 solution. It will begin producing EtONO gas which will travel up the pressure equalizing arm of the addition funnel, through the drying column, and into the reaction flask where it will condense into the EtOH. Don't worry if you don't see it drip from the condenser. The boiling point is 18C, so it will condense on the sides of the flask once it mixes with the EtOH vapors. Keep the temp of the rxn (reaction) flask at 30C.
5) Drip about 1/4 of the solution in the addition funnel. By this time, the solution in the reaction flask will have turned from orange-ish brown to a very dark brown, almost black color. Keep rxn flask at 30C. Now add 25 g of safrole to the reaction flask. It will immediately begin producing NO gas. This gas will travel up the condenser and into the bubbling apparatus. This apparatus should contain 3% H2O2 and baking soda. The H2O2 oxidizes the NO gas to nitrous acid, which is then neutralized to NaNO2, your hard-to-obtain starting material. Now ain't that fucking cool.
6) Continue to drip the contents of the addition funnel over the course of an hour (it really doesn't matter how long, just not too fast -- like more than 2 drops per second). The reaction will continue to produce NO gas for about 3 hours. Keep the rxn flask at 30C the entire time and run ice water through the condenser. This keeps EtONO from escaping. This must be done, or too much EtONO will escape and yields will suck. After it stops producing gas, a good deal of solid precipitate can be observed floating around in the solution. The reaction is done.
7) Now add 40 mL H2O and raise the temp to 50C for 45 minutes. This will hydrolyze the ketone as well as drive off any remaining EtONO.
Now for the workup:
1) Let the reaction mixture chill in the freezer. This will precipitate out more solids. Filter the cold mixture over celite (celite isn't necessary, it just makes it easier).
2) Flood the mixture with 10% HCl until it separates into two distinct layers. Keep adding until no more separation occurs.
3) Extract 3x with 30 mL DCM.
4) Wash DCM with 100 mL H2O.
5) Wash DCM 3x with 100 mL 5% NaOH. This will remove most of the black crap from the DCM. The DCM will turn a light brown color after the first wash.
6) Wash the DCM with 100 mL saturated NaCl. It turns dark red. This removes most of the residual water.
7) Dry with MgSO4 and filter.
8) Strip off DCM. You will be left with a very dark red, almost black, oil.
9) Add 10 mL stripped safflower oil and vacuum distill the ketone. Collect all volatile oils. Then fractionally distill the distillate to collect pure ketone. Yield is greater than 20g. Probably 22-23 g. Yield might improve, as this was my first time to get it working.
Well, that wasn't hard, now was it. Beats the hell out of benzo. To recover NaNO2, just crystallize it from the bubbler liquid.
After about a month of fucking around with KrZ's ethyl nitrite wacker, I finally got it working. And it works damn good. Not only is this method less messy than the benzo wacker but it also has the following advantages:
1) No need for benzo. Ethyl nitrite can be made from sodium nitrite, which is not that hard to get. Plus, the sodium nitrite can be regenerated from the NO gas generated by the reaction.
2) The yield is better.
3) Less PdCl2 is needed.
Now that it's perfected, this method is probably the best method around for making ketone. Here's the method that I have developed:
The glassware setup is fairly complicated, but I'll describe it as best I can. There are two parts to it -- A reaction setup and an EtONO (ethyl nitrite) generator. The reaction setup consists of a round bottom flask and a condenser. There should also be some way to input gas between the flask and the condenser. The top of the condenser should have a vacuum outtake attached to it to vent of the toxic NO gas that is produced.
The EtONO generator consists of a flat bottomed flask (round bottom will work too) with a pressure equalized addition funnel on top. A column packed with anhydrous CaSO4 is attached to the top of the addition funnel, and a vacuum outtake adapter should be connected to the top of the column. This vacuum adapter is then connected to the gas inlet on the reaction setup. The vacuum outtake on the reaction setup is connected to a bubbling apparatus or simply out the window. Fuck, that was pretty complicated huh? Too bad I don't have a picture.
Here is a breakdown of the method:
1) Add 140 mL anhydrous EtOH to the round bottom flask of the reaction setup. Now dissolve 775 mg anhydrous CuCl2 and 200 mg PdCl2 in the EtOH. You will have to let it stir for about 30 minutes at 30C to dissolve the PdCl2. When you first put the two solids in the EtOH, it will be a muddy brown color, with particles of PdCl2 floating around. After the PdCl2 is completely dissolved, the solution will turn an orange-ish color.
2) While you wait for the catalyst to dissolve, prepare a solution of 65 g NaNO2 and 160 mL H2O. Pour this in the flat bottomed flask of the EtONO generator.
3) Make a solution of 50 mL H2O, 50 g H2SO4, and 46 g EtOH. You must add the H2SO4 to the water first; then let is cool down and add the EtOH. Pour this solution into the addition funnel on the EtONO generator.
4) Once the PdCl2 is dissolved, run ice water through the condenser and begin dripping the contents of the addition funnel into the NaNO2 solution. It will begin producing EtONO gas which will travel up the pressure equalizing arm of the addition funnel, through the drying column, and into the reaction flask where it will condense into the EtOH. Don't worry if you don't see it drip from the condenser. The boiling point is 18C, so it will condense on the sides of the flask once it mixes with the EtOH vapors. Keep the temp of the rxn (reaction) flask at 30C.
5) Drip about 1/4 of the solution in the addition funnel. By this time, the solution in the reaction flask will have turned from orange-ish brown to a very dark brown, almost black color. Keep rxn flask at 30C. Now add 25 g of safrole to the reaction flask. It will immediately begin producing NO gas. This gas will travel up the condenser and into the bubbling apparatus. This apparatus should contain 3% H2O2 and baking soda. The H2O2 oxidizes the NO gas to nitrous acid, which is then neutralized to NaNO2, your hard-to-obtain starting material. Now ain't that fucking cool.
6) Continue to drip the contents of the addition funnel over the course of an hour (it really doesn't matter how long, just not too fast -- like more than 2 drops per second). The reaction will continue to produce NO gas for about 3 hours. Keep the rxn flask at 30C the entire time and run ice water through the condenser. This keeps EtONO from escaping. This must be done, or too much EtONO will escape and yields will suck. After it stops producing gas, a good deal of solid precipitate can be observed floating around in the solution. The reaction is done.
7) Now add 40 mL H2O and raise the temp to 50C for 45 minutes. This will hydrolyze the ketone as well as drive off any remaining EtONO.
Now for the workup:
1) Let the reaction mixture chill in the freezer. This will precipitate out more solids. Filter the cold mixture over celite (celite isn't necessary, it just makes it easier).
2) Flood the mixture with 10% HCl until it separates into two distinct layers. Keep adding until no more separation occurs.
3) Extract 3x with 30 mL DCM.
4) Wash DCM with 100 mL H2O.
5) Wash DCM 3x with 100 mL 5% NaOH. This will remove most of the black crap from the DCM. The DCM will turn a light brown color after the first wash.
6) Wash the DCM with 100 mL saturated NaCl. It turns dark red. This removes most of the residual water.
7) Dry with MgSO4 and filter.
8) Strip off DCM. You will be left with a very dark red, almost black, oil.
9) Add 10 mL stripped safflower oil and vacuum distill the ketone. Collect all volatile oils. Then fractionally distill the distillate to collect pure ketone. Yield is greater than 20g. Probably 22-23 g. Yield might improve, as this was my first time to get it working.
Well, that wasn't hard, now was it. Beats the hell out of benzo. To recover NaNO2, just crystallize it from the bubbler liquid.
