Making Testosterone from Androstenedione
- 01-04-2003, 10:32 PM
- 01-03-2004, 03:23 PM
I know this is an old thread, but has anyone tried this. I would be glad to but I don't have access to HPLC. I have friends at another lab that can run it for me though.
- 01-04-2004, 03:23 AM
01-05-2004, 10:37 AM
During my stint in Molecular Bio I studied steroid chemistry for two years.
This experiment is EXTREMELY hard to do even with the appropriate lab materials and here is why. (I acutally did this expeirment BTW... but I started even further back.. FROM CHOLESTEROL LOL)
The melting points of many of the intermnediates is extremely low... which means that many of the steps have to be performed under low pressure conditions to get a boiling point well below the temop. at which the compnmenets just turn to goo (Im trying to use laymans terms here... sorry)
I used a mercury vacuum and ice-salt baths and my eventual yield was EXTREMELY low...
many of the components some of you are talking about have to be COMPLETELY dry (i.e stored in sodium... very dangerous and VERY hard to get)
ANY water at all at ANY point in this experiment will completely destroy ALL your work.
TRUST me... this is a PAIN IN THE ASS.
If you want EASY homemade test without having to give yourself a stroke.. just do the extraction from the vet pellets 9synovex)... its much easier and you'll get a high yield... you can be sloppy and it still works.
LOL Im laughing to myself remembering what a pain in the ass it was to keep that ****ing methanol dry.
OH YES!!! one more thing
What the author FAILS to tell you!! is that you WILL have a considerable concentration of dihydrotest...
It would be very difficult to selectively reduce the 17 ketone group and NOT the 3 ketone group.
as a matter of fact you would have strange mixtures of all kinds of weird analogues from uncontrolled reductions and oxidations during various steps.
Oh... just to let you know... I had access to IR and an MR to determine purity... and of course high quality equipment to measue melting points.
It was a REALLY fun experiment though... I would rather inject toilet water (jk :-) )but seeeing that powdewr in the end was a total thrill.
01-05-2004, 11:54 AM
Well bro I've already ordered the Andro and I get the other chems free. I'm going to try it anyhow and see how it goes. I have access to IR & HPLC so I'll be able to test purity easily. I think your problem must have come from starting with cholesterol. I've seen the method for that and have no intrest in it...lol. I know there will be some radiance structures formed as byproducts, but they should be safe IMO. As for keeping chems dry, NaBH4 shouldn't be a problem, and Methanol doesn't seem like it would be difficult either. I agree about the syno conversion. This is just cheaper...if it works. I'll keep everyone posted on this thread as to how my experiment goes. It will take some time so just hold tight...
01-05-2004, 02:59 PM
cool. good luck.
make sure that sodium borohydride is super clean and sealed... if even a small amount of moisture got into the bottle (even from humidity) it will kill the reaction.
I used a similar compund (I cant remember exactly but it was an aluminum based catalyst) and the lid wasnt sealed properly... thanks to the humidity.. it ruined the compound and about 10 hours worth of work.
Make sure you have a good vacuum too.. I ended up breaking ours and sucked mercury through it LOL.
and yes starting from cholesterol increased the difficulty ten fold.
I still cant see how this reaction is going to selectively reduce that group. I would think you would have to protect the C-3 group and reduce c-17??? but I dont see a mechanism for doing that in the initial reaction??
Its been a LONG time so maybe Im just missing something.
01-05-2004, 03:11 PM
A bro at SM suggested this:
It can actually be a bit better than that. By doing the reduction in 30% methanol in dichloromethane at -78 deg C, a 93:7 mixture of testosterone to 3b,17b-diol can be obtained.
Reference: Canadian Journal of Chemistry, (1989), 67, 1206-1211.
I'll most likely try this if I can get some dry ice to get the temp low enough. As for the vacume, do you mean atmospheric pressure or just a filtration vacume? I plan on doing this reaction at atmospheric presssure, IOW in an open beaker.
01-05-2004, 04:29 PM
someone eles should try doing this post :
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
sondheimer et al.
1g 4AD + 100mL chloroform + 10g MnO2 = test base 100% after 2 hours shaking at room temp
yield is 93% when crystalized with methanol and filtered on paper
MATERIALS: (check www.sciencelab.com i don't know if they are the cheapest, but they have everything)
hotplate with built in stirrer
chloroform (can be cheaper grade)
thermometer (-10 to 150 degrees celcius, its like $4)
activated MnO2 (if this cannot be found, make your own from potassium permanganate and manganese sulfate. also need ether if you do this step)
funnel (holds filter paper)
earlmeyer flask with vacuum tube out side for vacuum filtering
now that is alot of MnO2 and it can be done with less. too simple you say, well your right its not that easy. the MnO2 available commercially is not always active. but the authors gave a method of preparing MnO2 that is easy and the product is very active and can be put in a stoppered jar with no loss of activity (those guys would make great homebrewers)
HOW TO MAKE MnO2:
take concentrated aqueous potassium permanganate and add to a stirred aqueous manganese sulfate solution kept at 90 degrees celcius (need a hot plate that has stirrer built in) until a slight excess was present (pink coloration of the supernatant liquid). stir at 90 degrees celcius for 15 minutes. filter, wash well with hot water, then methanol and ether. dry at 120 to 130 degrees celcius to a constant weight. it can be kept for several months in a well stoppered bottle with no loss of activity.
how to get concentrated aqueous potassium permanganate: take distilled water and and add potassium permanganate until not more goes into solution (this is where a magnetic stirrer comes in handy). if you added too much, just add more water until all is in solution. duh!
how to get aqueous manganese sulfate: same idea as above.
i am looking for a source of activated manganes dioxide so that the above does not need to be performed. once we get the manganes dioxide, all we have to do is mix the 4AD, MnO2 and chloroform in the ratios above, basically add the 4AD to chloroform on the magnetic stirrer and then add the MnO2 and leave it for 3 hours at room temp. add methanol to the solution and the test will crystalize and fall out of solution. filter and wash well with methanol. collect the filtrate and filter again on new filter paper and dry all the filter papers. if the filtrate still has crystals, filter with another paper. i would dry the first filter paper out well for a few days and weigh it. if its more than 80% yield, i wouldn't waste time trying to get the rest. if not, then take the filtrate and refilter to get rest of crystals. you kind of play it by ear. that's pretty much it.....oh yeah, don't forget to discard the powder properly as this is an experiment
it is possible that much less MnO2 can be used. this will mean that the reaction will have to sit longer maybe a day or two, i don't really know. this will have to be found out. i want to try this in the lab where i can measure the ultraviolet spectrum to determine how long the complete reaction takes with different amounts of MnO2 and chloroform so as to minimize cost.
01-05-2004, 04:30 PM
or try doing this : from superior muscle:
BOLDENONE CYPIONATE (fast acting EQ)
Step 1: 1-Test cyp is brominated in the 4 position with 2,4,4,6-tetrabromocyclohexa-2,5-dione in ether with catalytic HCl. The product is 4-bromo-1-testosterone cypionate. There are other methods to achieve this bromination as well but this one should work very cleanly with a minimum of side reactions.
Step 2: the bromide is eliminated to give the 4,5-double bond by stirring the above product in DBU for 10 to 20 minutes. The overall yield of bold cyp should be around 75 to 80%
Step 1: The bold cyp from above is stirred in boiling benzene with ethylene glycol and catalytic acid. A Dean-Stark trap should be used to remove water as it is formed. This protects the 3-one as an ethylene ketal.
Step 2: The above protected bold cyp is stirred in boiling methanol/water with NaOH to remove the cyp ester.
Step 3: The 17-OH is oxidized to a ketone with any of a variety of chromium VI reagents.
Step 4: The above 17-one is reacted with methyl magnesium iodide. The reaction is quenched with water and acid. Heating the mixture with the water and acid will remove the ethylene ketal as well, leaving you with methandrostenolone.
METHENOLONE CYPIONATE (Primobolin, although real primo is the enanthate, not the cypionate, I expect little difference in function.
Step 1: 1-Test cyp is reacted with tetramethyl dilithium pentacuprate (formed in-situ from CuI and meLi). The reaction is quenched with liquid bromine. The product is 2-bromo-1-methyl-DHT.
Step 2: The bromine is eliminated to give back the 1,2-double bond by stirring with DBU as in the synthesis of bold cyp. The product is methenolone cypionate.
1-Test base is reacted with tetramethyl dilithium pentacuprate (formed in-situ from CuI and meLi). The reaction is quenched with water to afford mesterolone in a single step.
Step 1: Starting with 1-test base, the 3-one is protected as the ethylene ketal as in the above synthesis of methandrostenolone.
Step 2: The 17-OH is oxidized to a 17-one with chomium VI reagent.
step 3: The 17-methyl is attached with methyl magnesium iodide and the crude reaction mixture is treated with water and acid to quench the reaction and remove the ketal protecting group. The product is 17-methyl-1-test.
Step 4: the 17-methy-1-test is treated with ozone in methanol and then NaOH is added. This allows the purification of the intermediate by recrystallization of the sodium salt. The result is that the double bond is cleaved to give a carboxyolic acid (salt) on one side and an aldehyde on the other. The salt is dissolved in water and acidified to pH=4. NaBH4 is added to reduce the intermediate aldehyde. The resulting alcohol will spontaniously close with the carboxylic acid to give the desired lactone ring. The product is oxandrolone.
17-methyl-1-test from above is reduced with lithium in liquid ammonia. The ammonia is carefully evaporated under a dry N2 atmosphere to give a dry, crystalline enolate. The enolate is dissolved in dry THF and treated with N-formylmorpholine to give oxymethylone as the product.
DROMOSTANOLONE propionate (Masterone)
Step 1: 1-test base is reduced with lithium in liquid ammonia. The ammonia is carefully evaporated under a dry N2 atmosphere to give a dry, crystalline enolate. The enolate is dissolved in dry THF and treated with methyl iodide to install the 2-methyl group.
Step 2: the dromostanolone resulting from step 1 is esterified with propanoyl chloride and pyridine to afford the product, masterone.
01-05-2004, 04:30 PM
or try this with ando only :
careful reduction of the androstendione with NaBH4 at low temperature will selectively reduce the 17-one to give you test directly without having to reduce everything and re-oxidize the 3-OH.
01-05-2004, 05:13 PM
doing ALL these reactions in reduced atmosphereic pressure in closed enviroments will greatly increase yields. Some of them have to be done at lower pressures though. the boiling point of some of the compounds is too high at standard atmospheric pressure and will just turn to a sticky yellow goo that yields nothing.
You will have to redo the calculations for lower boiling points and catalyst reductions.
LOL superior muscle makes it look so easy.
01-05-2004, 05:45 PM
Spidey from SM is a Phd in chemistry. He and I have been talking about some of the reactions that sicosico posted. Most are of interest to me, but one thing at a time. I have access to a large variety of chems for free, but not everything. Anyone who has ordered from fisher or such knows that chems are pricy. Sometimes shipping on hazardous chems are more than the chems! I would like to try most conversions, but only if it is at a minimal cost to me. Thanks for the info Milo. I'm still going to try this at atmospheric pressure as I want to see how things would go for the bro's who don't have access to a lab. I want to keep it as simple a possible.
01-05-2004, 08:13 PM
01-05-2004, 09:15 PM
01-09-2004, 09:46 AM
I finaly have all the chems together to do this. I'll pick up the dry ice tommorrow and get started. The only problem now is that all the labs I know and have done buisnes with don't test things like Testosterone. So now I'm stuck looking for a lab that will test it for me. So far the few I've called were not suspicious. Anyone have a lab in mind? Also, I'm concerned with having to ship it to a lab. Does anyone think I might have a problem with doing that?
01-11-2004, 05:29 PM
I'm in the middle of the conversion right now. I still haven't found a lab to test the product for me so I might have to go by MP. Here is the reaction scheme for anyone interested:
01-16-2004, 08:56 PM
My first attempt at this went aweful. I spilled lots of the crude product during the filtration process. Gravity filtration of this is impossible so I ended up using a vacume filter. My kitchen stank of evaporated MeOH & the acetic fumes burned my eyes. This isn't something to attempt without the proper equipment! My yield in the end was only around 2.5g of a white, epoxy type material. For MP testing I used Ethylene Glycol since its BP is 199C and pure Test's MP is 155C. The melting range of my product was 125C-127C which means that I didn't make TNE at all .
I still have 50g of Andro & all the chems I need to do the experiment again so I might do that soon. I might use a dry ice/acetone bath to cool the reaction to -72C next time to see if it makes a difference. I suspect that the place of error was in the evaporation of MeOH. Even at a rolling boil it was very hesitant to evaporate? Anyhow, I'm going to discuss this with Spidey from SM & see what we can come up with. I'm not giving up yet...lol
01-17-2004, 09:01 PM
01-17-2004, 09:20 PM
maybe you should centrifuge for filtration. how did vacuum filter in your kitchen?.......do u have buchner funnel and a vacuum?......if you have these equipments why did you boil the solution to get MeOH you can simply use vacuum filtration in a flask, then spread the powder in a watch glass and it will dry in 10 min, then you can wash the residue with water.Originally Posted by candle25
are you using recrystallization to get impurities out?
and maybe it sounds funny but wear goggles next time
01-17-2004, 09:36 PM
I took the solution to work and filtered it. I'm a chem E at a pretty nicely equiped lab. The procedures were to condense the MeOH/Test solution and then crystallize by the addition of water. The original abstract that this idea was taken from did so as well. It might not crystallize otherwise as the solution wouldn't be as saturated. Are you suggesting that I attempt to crystallize without condensing?
BTW, goggles don't help much with fumes....lol
01-17-2004, 10:03 PM
i dont think condensation is an important step here. it dosent matter if its saturated or not, i used 1g/1000ml concentration in my oraganic chemistry lab and it worked, but the trick is in choosing the solvent. the solvent should dissolve the solid in temperature higher than room temp (thus you boil it), in order to be able to recrystallize it again in regular room temp 30 c. I dont know if water is a good solvent (most androgens dont dissolve in water), alcohol maybe a better option, im not sure though because we used water to dissolve Benzoic Acid in my lab. i think the error comes from the choice of solvent, im not sure though maybe a more knowledgeable bro can comment on that.
if you need help with the exact recrystallization procedure i have an experimental organic chemistry lab book with steps of recrystallizing many organic compound. i can copy the exact steps from the book if you wish.
Last edited by x_muscle; 01-17-2004 at 10:25 PM.
01-17-2004, 10:35 PM
Thanks for the offer but I know how to re-crystallize. I used the method that is on the first post of this thread. MeOH is the solvent, but many organic synthisis reactions are carried out at lower temps. The MeOH dissolves the Andro and the NaBH4 in an ice bath. Then the acetic is added to catylize the reaction. I have the mechanism posted a few posts up. You might have synthisized Nerolin, which is simmilar in technique to what I'm trying here. I don't think this reaction is an Sn2 reaction though. Any ideas you have are appreciated though, as you can see that my first attempt was a failure.
01-18-2004, 02:13 AM
i synthesized naphthalene and Benzoic Acid, which is very similar to what you doing.....keep the good work bro, you are actually encouraging me study my chemistry. if i managed to get the materials maybe i will try it on my own
01-24-2004, 05:02 PM
I did some more research today and found that NaBH4 degrades quickly in MeOH. It is rather stable in EtOH though. Would it be a good idea to attempt this reaction in EtOH? I also ordered 15g Mn (IV) oxide in case I need to redissolve my crude product in dichloromethane and treat it with Mn. That should oxidize the over reduced portion back to TNE. Does anyone have any suggestions or ideas about this?
01-24-2004, 05:46 PM
More usefull info:
"Chemoselective Reductions with Sodium Borohydride. Aldehydes vs. Ketones." D. E. Ward and C. K. Rhee, Synthetic Communications, 1988, 18, 1927-1933.
Abstract: Aldehydes can be reduced in the presence of ketones by sodium borohydride in 30% ethanol in dichloromethane at -78 C. The selectivity is generally greater than 95%.
"A General Method for the Selective Reduction of Ketones in the Presence of Enones." D. E. Ward, C. K. Rhee, and W. M. Zoghaib, Tetrahedron Letters, 1988, 29, 517-520.
Abstract: Ketones can be reduced in the presence of conjugated enones by sodium borohydride in 50% methanol in dichloromethane at -78 °C. The selectivity is generally excellent. In favorable cases the reaction can be carried out at room temperature in dichloromethane with acetic acid as catalyst.
01-05-2009, 12:19 AM
01-05-2009, 02:25 AM
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