^Title^
I read a synth for DMT from tryptamine to DMT and it called for sodium cyanoborohydride, not exactly OTC. (I mean, I'm sure there's a way, but not without some work, I imagine.) I was reminded, then, of a thread about A--->MA with methyl chloride, the problem being that it would produce DMA. In this case, it would seem that is desired. Why can't chloromethane be used to make T into DMT?

Off the top of my head, you may run into problems with:

a) formation of the quaternary ammonium salt rather than the tertiary amine

b) methylation of the indole nitrogen

I dunno if either of these would be an issue, but they are something to consider, particularly if bio-assay would be your primary means of structural analysis....

sodium CBH is very OTC if you know where to look...

sodium CBH is very OTC if you know where to look...

No kidding. Nobody ever wants to give up a source, but how bout a hint? HW store? Pool chem? Photo chem? I'm happy doing my own searching, but perhaps a place to look...

Off the top of my head, you may run into problems with:

a) formation of the quaternary ammonium salt rather than the tertiary amine

b) methylation of the indole nitrogen

I dunno if either of these would be an issue, but they are something to consider, particularly if bio-assay would be your primary means of structural analysis....

It's times like this I wish I knew more o. chem, but I don't know much about either possibility. My question to possibility A is why doesn't that happen with the NaCnBH3 route?

Oh, I figured I'd ask, can you reductively dimethylate strecker degraded tryptophan using dimethylamine? The strecker degradation of tryptophan makes indole (3ethaldehyde?) I don't know if you can reductively methylate an aldehyde as opposed to a ketone, so any input would be great.

Oh, I figured I'd ask, can you reductively dimethylate strecker degraded tryptophan using dimethylamine? The strecker degradation of tryptophan makes indole (3ethaldehyde?) I don't know if you can reductively methylate an aldehyde as opposed to a ketone, so any input would be great.


Don't see why not...


My question to possibility A is why doesn't that happen with the NaCnBH3 route?


The answer to both questions is effectively covered here:


http://en.wikipedia.org/wiki/Reductive_amination


With reductive amination (= reductive alkylation), you are forming the imine (at least we'll assume this for our purposes), which is then reduced using an appropriate reagent.

When alkylating nitrogen directly, you can overshoot, leading to undesired, overreacted, side products.

http://www.totse.com/community/showthread.php?t=2110532&highlight=tryptophan

Check this thread out ;)

Oh, I figured I'd ask, can you reductively dimethylate strecker degraded tryptophan using dimethylamine? The strecker degradation of tryptophan makes indole (3ethaldehyde?) I don't know if you can reductively methylate an aldehyde as opposed to a ketone, so any input would be great.

Heh. Now you're thinking! :) Yes you certainly could! Google reductive amination, and go to some .edu site (forget the name now), there's a bunch of reactions that show you what happens and what you need to do with your imine. I know for certain that you can reductively aminate an aldehyde, but the process is different, the site will show you. I've been thinking about this reaction for a long time now (since JP told me about Strecker degradation, practically), but stopped when I saw that dialkyl amines of virtually any sort aren't as OTC as I'd like them to be (health store or bust is my motto :mad:).

any input would be great.

Okay.

I don't know if you can reductively methylate an aldehyde as opposed to a ketone

You're not reducing an aldehyde or a ketone. You're reducing an imine. ;)

dialkyl amines of virtually any sort aren't as OTC

If you haven't considered the similar principle of imine reduction in forming the alkylamine (wudda ya mean, liquor =/= health food?)... you might want to consider, say, hypochlorite oxidation of alcohols.

Could be a good read. Less substitution-dependent than the hoffman rearrangement, I hear, which is good enough for the first alkylation...

Okay.



You're not reducing an aldehyde or a ketone. You're reducing an imine. ;)





but is it an aldimine or a ketimine...? ;)

If you haven't considered the similar principle of imine reduction in forming the alkylamine (wudda ya mean, liquor =/= health food?)... you might want to consider, say, hypochlorite oxidation of alcohols.
Hmmm... Do you mean oxidizing a secondary alcohol to the ketone and then making an imine from some sort of primary amine that way? From what I've seen hypochlorite will oxidize all the way to the acid so you could only perform this with secondary alcohols, the only effective one (on the tryptamine) of which would be IPA. Or are you telling me to buy the imine directly? Or... just to use ammonia and the corresponding alkylcarbonyl(s) to make the dialkyl amine? That sounds like it would be pretty easy especially since the chains would need to be considerably short, but would over/underalkylation be a problem here?

Could be a good read. Less substitution-dependent than the hoffman rearrangement, I hear, which is good enough for the first alkylation...

Surely that's at least as suspicious as buying the amine itself, right? Would mild oxidation of primary alcohols or amidification of the corresponding acid be more effective? I guess it depends on the method of oxidation. Back to the drawing board.:mad:

I thought I might as well ask: How useful would it be to reductively aminate indole-ethanal (the Strecker-degraded product of tryptophan) with tryptamine itself? Too long of a chain to be of any use? Would just one N-substitution make it so ineffective as to be useless?

From what I've seen hypochlorite will oxidize all the way to the acid so you could only perform this with secondary alcohols

Formaldehyde. bp : -19.3°c
Methanol. bp : 64.7°c
Formic acid. bp : 100.8°c

Acetaldehyde. bp : 20.2°c
Ethanol. bp : 78.4°c
Acetic acid. bp : 118.1°c

Propaldehyde. bp : 47.9°c
1-Propanol. bp : 97°c
Propionic acid. bp : 141°c

...noticing a trend? ;)

I thought I might as well ask: How useful would it be to reductively aminate indole-ethanal (the Strecker-degraded product of tryptophan) with tryptamine itself? Too long of a chain to be of any use?

From the tryptamine perspective, yes. There's a good chance of it being active with completely unknown pharmacology or character, though. ;)

...there's one or two dopamine reuptake inhibitors with a fairly similar structure. That indolic nitrogen, however, makes the hope of a cocaine analog less certain...

Would just one N-substitution make it so ineffective as to be useless?

This is also usually not the best news for the tryptamines...

Formaldehyde. bp : -19.3°c
Methanol. bp : 64.7°c
Formic acid. bp : 100.8°c

Acetaldehyde. bp : 20.2°c
Ethanol. bp : 78.4°c
Acetic acid. bp : 118.1°c

Propaldehyde. bp : 47.9°c
1-Propanol. bp : 97°c
Propionic acid. bp : 141°c

...noticing a trend? ;)
Now I do! So you propose underoxidizing the starting alcohol and then distilling off the aldehyde? Sounds like a plan.

From the tryptamine perspective, yes. There's a good chance of it being active with completely unknown pharmacology or character, though. ;)
Not all hope is lost! :)

This is also usually not the best news for the tryptamines...

I've noticed that trend. At least with NMT/DMT. :( There's certainly a way to make a ditryptamine, but would steric hinderance play any part? If it causes decreased yields I'm fine because l-tryp is very cheap, but if l-tryp won't react at all with indole-acetal, then... :( Looking at it more it doesn't look like it, so... never mind.

Now I do! So you propose underoxidizing the starting alcohol and then distilling off the aldehyde? Sounds like a plan.

More or less. My original thought was more manic-OCD, but same underlying concept.

In fact, since, fuck it, let's admit it, we all wanted to do this since we were kids...

LET'S BUILD A MOTHERFUCKING SPACE FACTORY!!!

(yes. it should actually work in 0g. since I know you're curious)

http://img233.imageshack.us/img233/3315/factoryid7.gif

...was my inital thought... where...

1. Air intake. Special atmosphere, standard atmosphere, your choice.

2. Fan. This is just to maintain a gentle positive pressure.

3. Dimmer switch. Finely adjust the power flowing to the fan such that...

4. The plastic bag. It should be gently inflated, yet not straining and stiff, as the air passes through it into...

5. The vented conduit. Basically, PVC with vent holes. If the vent holes are present between the air driver (fan) and the downstream hardware, and if the bag is loosely inflated but not strained, you should have a suitably gentle positive pressure directing flow downstream to the...

6. Giant flask of methanol. Or other -ol. The temperatures in this post are based on methanol, however, 'cause I had to pick something. For most operations, this will be the very beginning of the temperature-controlled section, and it should be sitting around 40-50c. Sub-boiling, but good, constant vapor production through voilatilization, as it flows into...

7. Giant container of magnesium sulfate or similar. Just in case your methanol was only 90% or so. This should probably be kept at or above the temperature of the flask, to reduce flow loss from condensation. The boiling point of the substance as a temperature setting for this stage is acceptable and possibly even desireable, provided there is no leak to...

8. The fractionating column. That's right, a fractionating column... kept at 0c and packed with Ca(OCl)2. It hits it, it condenses, evolved formaldehyde starts boiling and a stream of concentrated formaldehyde gas in whatever carrier vapor you're using passes out of the egress of the column, at a constant rate of production and in decent capacity.

:) Something like that. 'cause getting industrial about shit is... well... okay... it's fun. 'n if you're worried about overoxidization somehow happening before the instant flash-boiling, well... you can clean acidic residues with a NaOH tube as a scrubber on the FC egress. It's just another stripped-down 20oz bottle or whatever, lol...

would steric hinderance play any part?

Prob. not, but...

if l-tryp won't react at all with indole-acetal, then... :( Looking at it more it doesn't look like it, so... never mind.

...why are you not decarboxylating the tryptophan beforehand, if your desired product is the decarboxylate?

Anyways... get some PVC and start crafting, boy. Chop chop. You have an aldehyde factory to create, operate, and try to maximize L/minute yield of... for the good of science!!!

Jesus christ that was awesome.

LET'S BUILD A MOTHERFUCKING SPACE FACTORY!!!
That was madness!:mad:

:) Something like that. 'cause getting industrial about shit is... well... okay... it's fun. 'n if you're worried about overoxidization somehow happening before the instant flash-boiling, well... you can clean acidic residues with a NaOH tube as a scrubber on the FC egress. It's just another stripped-down 20oz bottle or whatever, lol...
I see what you mean by that now, I was thinking of using other hypochlorite oxidation methods but never thought about Ca(OCl)2 as an in-situ oxidant, just NaOCl along with other oxidants.

...why are you not decarboxylating the tryptophan beforehand, if your desired product is the decarboxylate?

Anyways... get some PVC and start crafting, boy. Chop chop. You have an aldehyde factory to create, operate, and try to maximize L/minute yield of... for the good of science!!!

Yeah I meant to say tryptamine, but adding tryptophan first might still be a good idea because larger molecules tend to decarboxylate easier (just heat 'em up and go).

I'll see what I can do about the factory, don't think I have any fans lying around, but I'm sure I'll find one (or an alternative).

Anyways... get some PVC and start crafting, boy. Chop chop. You have an aldehyde factory to create, operate, and try to maximize L/minute yield of... for the good of science!!!

Sweet!

But a little over-engineered, no? ;)

More or less. My original thought was more manic-OCD, but same underlying concept.

In fact, since, fuck it, let's admit it, we all wanted to do this since we were kids...

LET'S BUILD A MOTHERFUCKING SPACE FACTORY!!!

(yes. it should actually work in 0g. since I know you're curious)

http://img233.imageshack.us/img233/3315/factoryid7.gif

...was my inital thought... where...

1. Air intake. Special atmosphere, standard atmosphere, your choice.

2. Fan. This is just to maintain a gentle positive pressure.

3. Dimmer switch. Finely adjust the power flowing to the fan such that...

4. The plastic bag. It should be gently inflated, yet not straining and stiff, as the air passes through it into...

5. The vented conduit. Basically, PVC with vent holes. If the vent holes are present between the air driver (fan) and the downstream hardware, and if the bag is loosely inflated but not strained, you should have a suitably gentle positive pressure directing flow downstream to the...

6. Giant flask of methanol. Or other -ol. The temperatures in this post are based on methanol, however, 'cause I had to pick something. For most operations, this will be the very beginning of the temperature-controlled section, and it should be sitting around 40-50c. Sub-boiling, but good, constant vapor production through voilatilization, as it flows into...

7. Giant container of magnesium sulfate or similar. Just in case your methanol was only 90% or so. This should probably be kept at or above the temperature of the flask, to reduce flow loss from condensation. The boiling point of the substance as a temperature setting for this stage is acceptable and possibly even desireable, provided there is no leak to...

8. The fractionating column. That's right, a fractionating column... kept at 0c and packed with Ca(OCl)2. It hits it, it condenses, evolved formaldehyde starts boiling and a stream of concentrated formaldehyde gas in whatever carrier vapor you're using passes out of the egress of the column, at a constant rate of production and in decent capacity.

:) Something like that. 'cause getting industrial about shit is... well... okay... it's fun. 'n if you're worried about overoxidization somehow happening before the instant flash-boiling, well... you can clean acidic residues with a NaOH tube as a scrubber on the FC egress. It's just another stripped-down 20oz bottle or whatever, lol...



Prob. not, but...



...why are you not decarboxylating the tryptophan beforehand, if your desired product is the decarboxylate?

Anyways... get some PVC and start crafting, boy. Chop chop. You have an aldehyde factory to create, operate, and try to maximize L/minute yield of... for the good of science!!!

BRIX WHERE SHAT: :mad:

Anyone have some stuff on solventless decarbolyxation of l-tryp?

Jesus christ that was awesome.

...I almost included the specs for computer-controlled mass extraction of tryptophan from sunflower seed.

Then I realized that as far as I knew, amino isolation from fresh-lysed soup was still a manual process... but I've got the custom computer peripherals and most of the equipment laid out up to the lysis. ;)

"Let's build a sunflower factory!!"

- 'Bob the Builder,' the most bizzarely-premised children's show on earth.

Sweet!

But a little over-engineered, no?

It's how I roll. ;) I don't get off my ass if it's not scientific-industrial overkill - just the kind of mental defective I am.

...and yes, it can cause problems functioning, lol.

That was madness!

:mad::mad::mad: THIS IS LAB TIIIIIIIIIPPPPPPPPPSSSSSSS!!!!!!!!!! :mad::mad::mad:

BRIX WHERE SHAT:

...were they indole-3-ethyl(n-methyl)forminime bricks?

Anyone have some stuff on solventless decarbolyxation of l-tryp?

Do you feel like making custom polymers? If so, I've got some stuff on computer-controlled credit-card-sized rackslot micro/nanotechnological fusion in closet-based cottage industry... if I have to take the fuckload of time to write it up.

Custom polymers + nichrome = aqueous-deposited dry decarboxylation of amino acids.

Basically, polyparaquinone.

Anyone have some stuff on solventless decarbolyxation of l-tryp?

I just thought it would be easier to strecker degrade and then aminate. If you have an endless supply of borohydride I guess.

I just thought it would be easier to strecker degrade and then aminate. If you have an endless supply of borohydride I guess.

Or unless you wanted to (http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6THS-4B6KDFW-2&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_version=1&_urlVersion=0&_userid=10&md5=5d36da29df465fc539a1f81cc4147893) make a,n,n-trimethyltryptamine from the alternation of alkylated and unalkylated cores of the US 1 cent piece.

...at least, if is happening what appears to be happening. Fascinating substitution on the surface of the metal. I'm wondering where the hydrogen came from, though...

...at least, if is happening what appears to be happening. Fascinating substitution on the surface of the metal. I'm wondering where the hydrogen came from, though...


I don't think this is surface chemistry, rather the in situ formation of the organozinc reagent through activation of zinc dust with TMSCl and subsequent insertion of the active zinc into the C-I bond, to form RZnI. The presence of the additives then allows the relatively non-nucleophilic organozinc iodides to react with the aldimines.

The "hydrogen" presumably comes during workup, or from traces of water in the reaction medium

I don't think this is surface chemistry

In the monoatomic sense? 'cause...

to form RZnI.

...I was thinking of it as Zn(R)(X), in relation to ZnX2.

The "hydrogen" presumably comes during workup, or from traces of water in the reaction medium

I'd love to track it.

In the monoatomic sense? 'cause...

Well... I spose you could say that - although i think perhaps this is an oxymoron... ;)


...I was thinking of it as Zn(R)(X), in relation to ZnX2.


where Zn(R)(X) is the same as RZnX...? or are we taking different roads here?

where Zn(R)(X) is the same as RZnX...?

Yup. Same shit, different viewpoint.

To me, the most beautiful and awe-inspiring way to look at this is a ZnCl2 reduction to an amine which is modified... watching the ZnCl2 waltz up to the imine, molest it gently, pick up a little Cl2 from the HCl present and devolve the metallic complex dropping H2 as it goes...

If you view a one of those, much-debated in what actually happens, as one of the Cl being, well... organic... (and the other one being an I, but who cares? lol)...

...it paints an interesting picture of the thing.

Now... I'm sure there are people out there who get bored of my childish awe, and I'm sure there are other people who prefer the awe of viewing it as a zinc-substituted gringard, essentially, rather than an organic/halogen-swapped clemmensen... sans uneccesary amalgams...

...but it's awe-inspiring to trip on... just all the different ways in which the thing might be viewed... frames of reference, one to the another, same thing, different world... kind of like "the LSD trip of the nuclear universe," as all possible frames of reference are viewed from one to the other, no?

Meh... just trippin' on shit. ;) n'mind...

Yup. Same shit, different viewpoint.

To me, the most beautiful and awe-inspiring way to look at this is a ZnCl2 reduction to an amine which is modified... watching the ZnCl2 waltz up to the imine, molest it gently, pick up a little Cl2 from the HCl present and devolve the metallic complex dropping H2 as it goes...

If you view a one of those, much-debated in what actually happens, as one of the Cl being, well... organic... (and the other one being an I, but who cares? lol)...

...it paints an interesting picture of the thing.

Now... I'm sure there are people out there who get bored of my childish awe, and I'm sure there are other people who prefer the awe of viewing it as a zinc-substituted gringard, essentially, rather than an organic/halogen-swapped clemmensen... sans uneccesary amalgams...

...but it's awe-inspiring to trip on... just all the different ways in which the thing might be viewed... frames of reference, one to the another, same thing, different world... kind of like "the LSD trip of the nuclear universe," as all possible frames of reference are viewed from one to the other, no?

Meh... just trippin' on shit. ;) n'mind...
Man, I wish it was you that molested me when I was seven, instead of my uncle.

Yup. Same shit, different viewpoint.

To me, the most beautiful and awe-inspiring way to look at this is a ZnCl2 reduction to an amine which is modified... watching the ZnCl2 waltz up to the imine, molest it gently, pick up a little Cl2 from the HCl present and devolve the metallic complex dropping H2 as it goes...

If you view a one of those, much-debated in what actually happens, as one of the Cl being, well... organic... (and the other one being an I, but who cares? lol)...

...it paints an interesting picture of the thing.

Now... I'm sure there are people out there who get bored of my childish awe, and I'm sure there are other people who prefer the awe of viewing it as a zinc-substituted gringard, essentially, rather than an organic/halogen-swapped clemmensen... sans uneccesary amalgams...

...but it's awe-inspiring to trip on... just all the different ways in which the thing might be viewed... frames of reference, one to the another, same thing, different world... kind of like "the LSD trip of the nuclear universe," as all possible frames of reference are viewed from one to the other, no?

Meh... just trippin' on shit. ;) n'mind...

thoughts...


Lovely! Awe is always kinda inspiring - just as differing viewpoints are!

Personally, I prefer to look at it as the additive-promoted addition of an organozinc reagent (that's a "zinc-substituted grignard" to you ;) ) to the imine, partly because the Zinc in the "reduction" model would have to be acting in a very "Transition metal-eqsue manner" in order to follow that pathway, undergoing reductive elimination to the product.


Though the Clemmenson reduction of the imine should go through to the alkane, perhaps the oxophilicity of zinc is a driving force for complete reaction, and thus imine to amine is feasible...

As ZnCl2 would almost certainly be present in the reaction mixture, I wonder if an amalgam is strictly necessary to promote the Clemmenson, or whether reasonably finely divided material in excess would do the job...

will reply moar l8r, but...

As ZnCl2 would almost certainly be present in the reaction mixture, I wonder if an amalgam is strictly necessary to promote the Clemmenson, or whether reasonably finely divided material in excess would do the job...

http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv6p0289

Looks good.

...were they indole-3-ethyl(n-methyl)forminime bricks?


What ya think ;)

I just thought it would be easier to strecker degrade and then aminate. If you have an endless supply of borohydride I guess.

I wish i had an endless supply :mad: i have a bit tho'

Von Bass can you please link me up again to the tryptophan --> DMT using formalin and NaBH4?

Man, I wish it was you that molested me when I was seven, instead of my uncle.

lol wut?


As ZnCl2 would almost certainly be present in the reaction mixture, I wonder if an amalgam is strictly necessary to promote the Clemmenson, or whether reasonably finely divided material in excess would do the job...

=

will reply moar l8r, but...



http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv6p0289

Looks good.

Sounds good to me too, although amalgam is not that bad to run too but sure thing dealing with no mercury is a +!

Sounds good to me too, although amalgam is not that bad to run too but sure thing dealing with no mercury is a +!


Yeah - looks peachy!

For some reason I had in my head that the Clemmenson reduction requires the presence of ZnCl2 for promotion, but now I think not, and that the presence is simply incidental.

Totally reasonable for it to work simply through activation of the zinc and it appears, as in most cases, the amalgam is only a means to access very finely divded zinc (though sometimes the almagam is chosen to increase solubility).

On another note - I really like Organic Syntheses - I think the ethos behind it is admirable and in stark contrast to most journals (particularly those outside of the ACS or RSC remit)

Yeah - looks peachy!

For some reason I had in my head that the Clemmenson reduction requires the presence of ZnCl2 for promotion, but now I think not, and that the presence is simply incidental.


Nope, confusing yourself sir ;)



On another note - I really like Organic Syntheses - I think the ethos behind it is admirable and in stark contrast to most journals (particularly those outside of the ACS or RSC remit)

I love it, its in my tabs for a reason or what ;)