Andro to TNE...Spidey??

[candle25]

How to convert Androstendione to TNE

Editor's Note: In the US, this chemical procedure is illegal. Additionally, the by-products of the various androstenediols may fall under the Federal Analogue Act, which schedules derivatives of any DEA-controlled drug (in this case testosterone) into a Control I substance. So in effect, this procedure outlined is a hypothetical exercise designed to show a possible conversion of androstenedione to testosterone.

The procedure outlined below won't convert 100% of androstenedione to testosterone. But it will convert at least 60% of it, if the procedure is not screwed up too badly. The other percentage of finishied product will contain a small amount of unreacted androstenedione and a larger amount of a (epimeric) mixture of 3,17-androstenediols, which, fortunately, are safe and considerably anabolic compounds in their own right.

Materials Needed
Androstenedione (powder)
Methanol (wood alcohol)
Sodium Borohydride (sodium tetrahydroborate)
Acetic Acid (ethanoic acid)
Distilled Water
Litmus Paper
Thermometer (Fahrenheit)
Also: Beaker or glass container for the reaction a pot for salt water ice bath, a way to stir (i.e. spoon), filter, eyedropped (1 or 2cc size).


Procedure
1)10 grams of androstenedione is dissolved in 400ml methanol and cooled to 32deg Fahrenheit in a salt/ice bath (similar to chilling home-made ice cream).

2)2.5g sodium borohydride is added while the solution is stirred.

3)The solution is continually stirred for 45 minutes while the temperature is maintained as close to 32deg Fahrenheit as possible.

4)After 45 minutes, acetic acid is added to the solution, while stirring, in increments of approximately 2ml at a time (hydrogen gas will evolve).

WARNING!
Hydrogen Gas can ignite from flame or spark.

5)After each addition of acetic acid, thepH of the solution should be checked.

6)When the pH just begins to turn acidic on the litmus paper, then the addition of acetic acid should be stopped.

7)The methanol solution is now concentrated by evaporation until the volume is around 50ml.

WARNING!
Hydrogen gas may still be present; it can ignite from flame or spark.

8)This concentrated methanol solution is then mixed with 700ml water.
The cloudy precipitate that forms is filtered off and the filter cake is washed extensively (several times) with water.

9)The filter cake can be air (sun) dried for several days or dried in an oven for several hours at a temperature no higher than 150deg Fahrenheit.

The finished product, a fine white powder, should contain approximately 60 to 80% testosterone, with lesser amounts of unreacted androstenedione and a mixture of 3-alpha, 17-beta, and 3-beta, 17-beta androstenediols.


What should be done with this (now highly illegal) stuff once the procedure is finished?

Since it is highly illegal I would advocate getting rid of it.

Yet if someone wanted to take the risk and decided to use it, they would probably wonder if it should be taken orally or what?

I would not suggest that anyone take it orally because the purpose of the experiment would be defeated. Since testosterone is mostly deactivated in the gut, the ingestion of the finished product would be worthless. Instead, there are better alternatives, such as making sublingual liquid by dissolving the product in a solvent such as propyleneglycol and/or ethanol. If this is done, I suggest aiming for a concentration of around 30mg/ml and taking one-third of a milliliter (about 33 insulin IUs) under the tongue as a single dose (repeated throughout the day as often as wished by the user). Another alternative is to make a transdermal DMSO solution (messy and stinky). A third course of action (for the bold ones) is to make an injectable solution.

[spidey]

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.

[candle25]

That's why I posted this. I knew you'd have some great idea! Do you know of a place online that I can read the Journal that you mentioned? I'd like to compair the process and see if there are any other differences. Also -78C (-108.4F) seems like it would be hard to maintain. Any ideas on that other than an ice/salt bath?

[spidey]

Go to your local university chemistry library and look it up there. It's a very common journal and any such library would carry it. You could try searching PUBMED for it. The authors are Dale E. Ward and Chung K. Rhee. The title of the article is "Chemoselective reductions with Sodium Borohydride".

-78 deg C is not hard to maintain. That is the temperature of a dry ice/acetone bath. You will find that is a fairly common constant temp bath used in synthetic chemistry. Ice/salt baths can only get down to about -20 deg C (and even then it is tricky).

[candle25]

I'm a student at a great university with such a library. It's just such a long drive. As for the acetone/dry ice bath, I can get the acetone for free, but the dry ice is another story. I'll search the internet and see if I can find a supplier. I have an account with Fisher & Acros as well.

[spidey]

you might try to look up gas suppliers in the yellow pages. We get ours from a company called Airgas dry-ice

[candle25]

OK, I have all my supplies but dry ice. I called our gas supplier just now and BOC doesn't carry dry ice. However, they do carry liquid N. 180L for $40. My salesman said he'd loan me a 6' SS hose and diffuser to transfer it with. I have a 4L SS beaker I was thinking of doing the reaction in. I'm not really liking the idea of sinking another $40 in this project. What type of results do you think I'd have if I used a salt/ice bath? In all honesty, this conversion is highly impractical. I get all these chems free, but for soemone who doesn't it would cost out the a$$.

[spidey]

Liquid N2 is way too cold. It will just freeze everything solid.

Try http://www.dryicedirectory.com/ . Just type in your area-code at the top and it will tell you if there is anyone in that area-code who sells dry-ice.

It shouldn't be that hard to find. It's used for many legitamit projects from making your own root-beer to making fog special effects in your jacuzzi.

As for the chemistry costing a lot, not if you consider that for a hundred bucks or so you can buy enough reagents to make kilograms of material.

[spidey]

BTW, you could just do the reaction at warmer temperatures. You will get a larger amount of the over-reduced diol but you can take that crude product mixture and dissolve it in dichloromethane and add 5x by weight of MnO2. Stirr for 24 hours at room temp and then filter off the MnO2. That will oxidize any diol to the 3-keto-17-ol steroid.

[candle25]

Thanks for the link spidey. I found a supplier very close using it. It's dirt cheap too. $0.93/lb at a 6lb minimum. So I'm going to pick it up tommorrow and get this thing started. I'm only going to have to maintain the low temp for about 1hr so I don't think that will take much. I have 60g of andro so I'll prob do several batches just to get used to the process. One thing I'm concerned about is the glassware I'll be using. Do you think it will withstand the low temp? I use kimax and pyrex beakers from fisher. Also, I overlooked the fact that I need methylene chloride. I'm going to go by the hardware store and look at paint strippers. Would that be a bad idea?

[spidey]

Originally posted by candle25
Thanks for the link spidey. I found a supplier very close using it. It's dirt cheap too. $0.93/lb at a 6lb minimum. So I'm going to pick it up tommorrow and get this thing started. I'm only going to have to maintain the low temp for about 1hr so I don't think that will take much. I have 60g of andro so I'll prob do several batches just to get used to the process. One thing I'm concerned about is the glassware I'll be using. Do you think it will withstand the low temp? I use kimax and pyrex beakers from fisher. Also, I overlooked the fact that I need methylene chloride. I'm going to go by the hardware store and look at paint strippers. Would that be a bad idea?

I sort of doubt you will find paint stippers that are pure dichloromethane. Do you have access to chloroform? That will work as well but you must remove the ethanol which is used to stabilize it first. That is easily done by washing the chloroform with 3 portions of water in a separatory funnell and then drying the chloroform over MgSO4.

[candle25]

I happen to have chloroform but I have no MgSO4...lol. It looks like I'll have to wait untill I can get the methylene chloride. I could call my old Chem teacher and ask to buy what....half a L? I'd have to have a good reason for needing it and I really can't think of one.

[spidey]

Actually, I made a bit of an error here I think. I was thinking you needed the methylene chloride for the MnO2 oxidation but you are going to use it in the NaBH4 reduction, right?

Chloroform WILL NOT work in the NaBH4 reduction and may even be dangerous. Chloroform forms carbenes quite readily under basic conditions which are very reactive.

As for how much dichloromethane you need, read that paper and keep the ratio of dichloromethane to 4-AD the same in your reactions. Do the calculation on how much 4-AD you want to reduce and then you will know how much solvent is needed.

Oh yeah; the kimex and pyrex glassware you have will stand up fine to -78 deg C. Do you have a magnetic stirrer?

[spidey]

It may be easier and cheaper to do this at warmer temps the way you originally planned (but with excess NaBH4) to get your mixture of diol and test and then submit the whole lot to MnO2 oxidation overnight with 5x by weight MnO2. This will oxidize all the diol to test.

[candle25]

I'm not doing the 4AD conversion, we talked about that on a different thread. I'm doing andro to TNE. As far as I know MnO2 isn't needed. The very first post on this thread outlines what I'm attempting in detail. So are you saying I need MnO2? If so I have about 2g of Mn (IV) oxide. That's the same thing I think.

[spidey]

You are reducing andro with NaBH4, right? You will end up with some over-reduced diol. The MnO2 (Mn(IV)oxide) will oxidize the diol in your product mixture to TNE.

So, no, you don't "need" it if you are willing to settle for some amount of androstenediol in your product.

[candle25]

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 did the experiment just as I have it written out in the first post. I don't understand what went wrong. Maybe my glassware wasn't clean anough? Maybe the temp that I did the reaction at? Everything seemed to go well untill the MeOH evaporation process. I had to get a rolling boil just to get it to evaporate. A white foam formed around the edges of my evap dish while I was evaporating the MeOH. You have any suggestions Spidey? Anyone? I have plenty of the chems left, so I can do it several more times.

[candle25]

I did a little more research today and found that NaBH4 degrades quickly in MeOH. I also found that NaBH4 is stable in EtOH. Would it then be better to react the Andro & NaBH4 in EtOH? I really want to try this again, but I need to have it nailed down before I attemt it. I also ordered 15g Mn (IV) Oxide yesterday. So if I need to redissolve the crude product in dichloromethane and treat it with the Mn.

Found this as well:
"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.

[spidey]

Originally posted by candle25
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 did the experiment just as I have it written out in the first post. I don't understand what went wrong. Maybe my glassware wasn't clean anough? Maybe the temp that I did the reaction at? Everything seemed to go well untill the MeOH evaporation process. I had to get a rolling boil just to get it to evaporate. A white foam formed around the edges of my evap dish while I was evaporating the MeOH. You have any suggestions Spidey? Anyone? I have plenty of the chems left, so I can do it several more times.

Just because your melting point was low doesn't mean you didn't have some product. It just means it wasn't pure.

NaBH4 is not completely stable in ethanol either but it is more stable in ethanol than methanol.

Do you have analytical TLC plates? You really need some way of judging when your reaction is complete.

[candle25]

No. I have no TLC plates. Are they expensive? I might buy some if they don't cost too much. Do you think that I didn't let it react long enough? I can let it react longer next time. Thanks for helping out with this experiment. You are the only person on 4 boards that pays any attn to chem related questions.

[spidey]

I would buy the aluminum backed flexable plates you can cut with scissors. They are generally bought as packs of 25 (25x25cm) and I can get 24 individual TLC plates from one 25cmx25cm sheet.

The cost from Fisher Scientific is $132.14. That may seem expensive but not when you consider that is 600 individual TLC plates when you cut them up. That should be a lifetime supply for you.

Catalog number is M5554-7 for Silica gel-60 TLC plates, packs of 25 sheets with fluorescent indicator.

To do TLC, you will need a clear jar with a lid to use as the developing chamber and a staining agent or UV-lamp.

10% KMnO4 in water will do as a staining agent. You dip the developed plate in the KMnO4 solution and then heat with a heat-gun or hot-plate until the spots show up as yellow spots on a pink or maroon background. Careful not to overheat or the whole plate will turn yellow and you won't be able to see anything.

If you need detailed directions on how to use TLC to check the progress of your reaction, let me know.

[candle25]

I might be able to order them through my job and write it up as a lab expense. The only problem I see with this method is that it is starting to become unpracticle. The expenses for all the reagents and tools I have bought (well had bought..lol) for this experiment are getting to be higher and higher. I personally have a small, decent lab at home, but I doubt the average guy will have all the equipment that you or I have access to. I'll look into the plates and post back when I get them. I was reading in an organic sythisis book yesterday at work about how to use TLC plates to tell if a reaction is completed. If I have any questions I'll post them as well.

[spidey]

Think about it like this:

It is expensive initially but the equipment and reagents you buy are enough to make enough AS for literally dozens of cycles. How much would you spend buying the AS from a source for 12 cycles?