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IndoleAmine
Dreamreader Deluxe
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| Joined: 09 Feb 2005 |
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18717.10 Points
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Sun Mar 20, 2005 7:19 am |
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Starlight: I thought the pictet-spengler between tryptamines and formaldehyde would favorably occur under basic conditions? But before I become criticized for this statement: I'm not sure about it.. 
But something interesting I found in the patent Lief provided us with:
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A number of methods are available for "aminoethylation," the attachment of a 2-carbon ethylamino group to an indole ring. Reaction of an indole with a strong base, such as a Grignard reagent, followed by reaction with aziridine directly gives the aminoethylated product in fair-to-moderate yields. Conjugate addition of an indole to nitroethylene followed by reduction of the nitro group achieves aminoethylation in two steps, although the reduction conditions for the nitro group are not compatible with certain other functional groups. Three-step procedures include the initial formation of an indole-3-carboxaldehyde, followed by condensation with nitromethane and subsequent reduction of both the double bond and nitro groups, as well as initial attachment of a (dimethylamino)methyl group to form a gramine derivative, followed by displacement with cyanide and reduction of the resulting nitrile to the amine.
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Now we can choose which route we prefer, and then aquire the necessary refs to learn the essential details, I guess? (I for my part would vote for one of the two last alternatives; going via the aldehyde and then henry with NE and reduction with LAH, or makin gramine via mannich, doin that cyanide replacement  and converting the nitrile to the amine)  
i_a |
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ApprenticeCook
DILLIGAF
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| Joined: 12 Feb 2005 |
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| Location: Australia |
8486.38 Points
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Sun Mar 20, 2005 7:35 am |
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Synthetic.... Indoleamine.... do i have to send you both to your rooms again?
So this wont work? Ah well.... was a pipe dream....
-AC |
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IndoleAmine
Dreamreader Deluxe
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| Joined: 09 Feb 2005 |
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18717.10 Points
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Sun Mar 20, 2005 8:48 am |
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| IndoleAmine wrote: |
:
Indole --(elbs persulfate oxidation(?))--> Indol-3-yl-carboxaldehyde
Indole-3-aldehyde + MeNO2 -(knoevenagel/henry)-> indol-3-yl-2-nitroethene
--(LAH reduction)--> tryptamine
i_a
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elbs persulfate oxidation is AFAIK used to make phenols, can you make indolcarboxaldehyde this way? is there a reference?
Then from indolecarboxaldehyde you again remind us that we can use LAH in order to prepare tryptamine, thanks. Besides, for any N,N-dialkyl tryptamine, it is better to go via tryptophol, tosylate and do a simple sn2 with the sec amine of your choice, chemicals are not hard to get, and besides there is a route using a certain pigment (that needs no attention) that is over the counter. so your proposal really sux, uses heavily watched chemicals and is nothing new.
| IndoleAmine wrote: |
..to circumvent the problem of cyclization during dimethylation of tryptamine (remember Liliental always said NaBH4/HCHO would result in betacarboline due to pictet-spengler): make a quaternary tryptammonium salt, and selectively demethylate to get the dimethyl derivative of this indoleamine..... 
(I think this was the only known solution of this problem, at the time the hive went offline; but if I'm wrong here I would be glad to hear it!)
i_a
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So what? This has allready been covered in the DMT entry in Tihkal: http://www.erowid.org/library/books_online/tihkal/tihkal06.shtml
And regarding tropinone discussion, here you can see the mechanism of the Robinson tropinone synthesis:
http://holivo.pharmacy.uiowa.edu/reaction/robinson.pdf |
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starl1ght
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| Joined: 27 Feb 2005 |
| Posts: 9 |
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0.00 Points
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Sun Mar 20, 2005 4:39 pm |
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| Lief wrote: |
See the following:
Example 27
See column 5 lines 35+ here:
See example 32 on page 27 here:
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Lief,
Just because it's in a patent as a procedure (hypothetical procedure I think), does not mean it works.
Tryptamine + HCHO ------[H+]----> a beta-carboline.
A carbon-carbon bond is formed between the formaldehyde imine and the 2-position of the indole nucleus. |
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IndoleAmine
Dreamreader Deluxe
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| Joined: 09 Feb 2005 |
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18717.10 Points
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OK - then...
Sun Mar 20, 2005 5:06 pm |
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Then from indolecarboxaldehyde you again remind us that we can use LAH in order to prepare tryptamine, thanks.
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My point wasn't to mention the usefulness of LAH as a reducing agent, but rather the trick of forming a QUATERNARY tryptammonium salt, followed by selective demethylation, to circumvent the problem of pictet-spenger cyclization during methylation of tryptamine - but one often just reads what one wants to see, right?
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Besides, for any N,N-dialkyl tryptamine, it is better to go via tryptophol, tosylate and do a simple sn2 with the sec amine of your choice, chemicals are not hard to get, and besides there is a route using a certain pigment (that needs no attention) that is over the counter
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You wanna say something useful? Maybe about MnO2 oxidations?
Then come on, get started and stop speaking in cryptic terms nobody can understand.
i_a
Last edited by IndoleAmine on Wed Mar 23, 2005 8:27 am; edited 1 time in total |
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IndoleAmine
Dreamreader Deluxe
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18717.10 Points
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Sun Mar 20, 2005 5:13 pm |
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Oh, synthetic - and the tropinone synth is of NO interest with regards to this topic, it just shows quite clearly why the mannich can't be used for aminoethylations.
The fact that something has been covered in TiHKAL doesn't mean it mustn't be discussed again here, besides.
Thanks for the links anyway.
i_a
Last edited by IndoleAmine on Fri Mar 25, 2005 6:59 pm; edited 1 time in total |
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IndoleAmine
Dreamreader Deluxe
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| Joined: 09 Feb 2005 |
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18717.10 Points
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Re: OK - then...
Sun Mar 20, 2005 6:00 pm |
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| IndoleAmine wrote: |
Listen well, synthetic:
we don't want no childish disturbances of any scientific discussion just because of personal dislike and greed; so please think about what you really have to say BEFORE posting anything next time, since pure criticism doesn't help and creates a hostile atmosphere...
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Mentioned alternative route. But you seem to have different interests.
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You are not the one to decide what "sux" and what not. Mind your own business please, its not my problem if you can't get certain reagents.
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Having an opinion is a crime?
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AFAYK maybe; but then again you don't know everything. It makes aldehydes, alcohols, ketones even from hydrocarbons. ("D'OH!")
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So you can make the idolecarboxaldehyde from indole using this reaction as you suggest? Prove it. Maybe you are confusing this with the benzaldehyde synthesis from toluene or benzylalcohol? You see, there is an extra carbon missing in your equation.
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My point wasn't to mention the usefulness of LAH as a reducing agent, but rather the trick of forming a QUATERNARY tryptammonium salt, followed by selective demethylation, to circumvent the problem of pictet-spenger cyclization during methylation of tryptamine - but one often just reads what one wants to see, right?
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Yes, we can read the detailed procedure in tihkal..
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You wanna say something useful? Maybe about MnO2 oxidations?
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???
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Then come on, get started and stop speaking in cryptic terms nobody can understand.
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Too bad, try to understand it at least, it is a really nice route... I can dig up the papers if you want.
Last edited by Guest on Sun Mar 20, 2005 11:45 pm; edited 1 time in total |
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IndoleAmine
Dreamreader Deluxe
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18717.10 Points
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Sun Mar 20, 2005 6:13 pm |
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You still don't seem to get it.
Its not "having your own opinion" - it is just and simply your choice of words that make you look like an asshole (and I don't want to be insultive here; it was/is just my personal impression, and I'm sad that it is)
Without any further stupid citations of the rhethorical opponent's words:
If you think you have a better route at hand, we all would be glad to hear about it.
If you think I am wrong with my statements, tell me in a polite way and noone will ever complain.
Yes, I want you to dig up papers.
No, I'm not sure whether an elbs oxidation will do the job, therefore I put a little question mark in brackets behind this statement, just like that (?).....
Possible that a reimer-tiemann or any other well-known oxidation might turn indole into indol-3-yl-carboxaldehyde - I am sure there are many options here, so I didn't bother finding a specific one.
I hate yeast, so the tryptophol doesn't appeal to me.
Do I attack you because of that?
No.
Please be/stay polite, and we're fine.
i_a
Last edited by IndoleAmine on Fri Mar 25, 2005 7:02 pm; edited 1 time in total |
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IndoleAmine
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tryptophol routes
Mon Mar 21, 2005 12:34 am |
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tryptophol - lets see...
tryptophol intermediates: they can for example be brominated and then reacted with dimethylamine to give the desired compound...
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"phosphorous tribromide in ether or benzene converts tryptophols into 3-(2-bromoethyl)indoles in good yield, and subsequent reaction with ammonia or amines makes a wide array of tryptamines available."
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("Hydroxyindoles, Indole Alcohols, and Indolethiols" Spande, Thomas F. in: The Chemistry of Heterocyclic Compounds: A Series of Monographs Vol. 25, Part III: Indoles, Part III, 1979.
)
And they are easily made by reduction (sodium/EtOH, or LAH, maybe NaBH4 etc.) of idoleacetic acid alkyl esters.....
(which in turn can be easily made from IAA, excess alcohol and a bit H2SO4)..
Further, tryptophol can also be boiled with excess of an alkylamine, in xylene over a nickel catalyst, to give indol-3-yl-alkylamines - problem is just the volatility of dimethylamine, which can probably be circumvented by using dimethylammonium acetate, who knows.....
V.I. Shvedov, L.B. Altukhova, L.A. Chernyshkova, and A.N. Grinev, J. Org. Chem. USSR, 5, 2158 (1969))
General procedure for the preparation of dialkyltryptamines:
Into a flask fitted with a Dean-Stark recieving trap were placed 0.1 moles of tryptophol [2-(3-indolyl)-ethanol], 0.1 moles of a secondary amine [dimethylamine for DMT], 4ml of skeletal nickel [Raney Ni] suspension in water and 100ml of benzene or xylene [I assume toluene is good too]. The reaction mixture was refluxed, and the condensed water collected for four hours, the hot solution filtered and the catalyst washed repeatedly with benzene or xylene [or toluene] and the mother liquor concentrated under vacuum. The product was either distilled in vacuo or isolated as the hydrochloride by acidifying with an equivalent of hydrogen chloride solution [they are probably referring to a non-aqueous HCl solution here]. The yields were in the 82-98% range."
And another example for the whole procedure, exemplified with N-methyltryptamine:
"3-(2-Methylaminoethyl)-indole (N-Methyltryptamine)
JACS 78, 3668-72 (1956)
Methyl 3-indoleacetate was obtained from 3-indole-acetic acid following the esterification procedure of Jackson [14] The yield from 30.0 g. of acid was 28.6 g. (89%) of colorless oil, b.p. 160-163°C/0.9mmHg, reported [14] in the neighborhood of 180°C/2mmHg.
Tryptophol. Reduction of the methyl ester with lithium aluminum hydride was carried out in a usual way to yield 96% of colorless solid melting at 58.5-59.5°C. Recrystallization from benzene raised the m.p. to 59-60°C. This material has been prepared by reduction of the ester with sodium in alcohol [15] and by reduction of the acid with lithium aluminum hydride in 65% yield [16] (reported m.p. 58-59°C, 57-58°C).
3-(2-Bromoethyl)-indole was prepared according to Hoshino [15]. From 3.0 g. of tryptophol there was obtained 3.5 g. (81%) of colorless material melting at 100-102°C, reported [15] m.p. 98-99°C, yield 60%.
N-Methyltryptamine was prepared by the method of Hoshino [16] by heating the halide with methylamine at 100°C in a sealed apparatus. The yield of pure amine was very poor (ca. 5-8%), m.p. 89-90°C. The reported m.p. was 89-90°C, with no yield given [15]. The orange picrate melted at 193-195°C after recrystallization from methanol; reported [15] m.p. 190-191°C."
Indoleacetic acid is made as follows (for example):
US Pat 3,320,281
"Into a 0.5 lit. pressure vessel were charged 5.85 g.(0.05 mole) of indole, 14 g. (0.15 mole) of chloroacetic acid and 150 ml, of 17% aqueous solution of potassium hydroxide. The reactor was next charged with nitrogen to a pressure of 5 atm. and the reaction mixture was heated to 285-290°C. and maintained at this temperature for 15 hours, the pressure in the reactor being 85-90 atm. Then the reaction mixture was cooled, discharged from the pressure vessel and filtered. The filtrate, with external cooling, was acidified with concentrated hydrochloric acid, until it showed an acid reaction to Congo red, and maintained for 2-3 hours at a temperature of 8-10°C. The precipitated crystals of 3-indolylacetic acid were filtered off, washed on the filter with ice water until the washing water was acid-free, and dried. The product consisted of 4.52 g. of a white crystalline compound (mp 159-162°C.). The yield was 51% of the theoretical (on the basis of indole used)."
So now we can make indoleacetic acid from indole (or tryptophan), and esterify it with any aliphatic alcohol we like, then reduce the obtained ester with known reduction methods to get tryptophol.
Or one could start a fermentation of tryptophan somehow, but that's not my territory...
then brominate the tryptophol and aminate (sounds almost as crappy as the bromosafrole route to MDA, but who knows) to get DMT. But there's still the problem of cyclization...
And besides protecting the whole as a quaternary ammonium salt, it can also be done by forming the acetamide, followed by "deacetylation" with LAH:
"N,N-Dimethyl-3-indoleacetamide
JACS 78, 3668-72 (1956)
A mixture of 16.0 g of methyl 3-indoleacetate, 100 ml. of ethylene glycol and 19.4 g. of anhydrous dimethylamine was stirred at room temperature for 40 hr. The mixture was poured into 100 ml. of water and estr:tctcd with five 100-ml. portions of ether-ethyl acetate (1:1). This extract was washed with a little water, dried and evaporated to give a red oil. This was taken up in warm ethyl acetate and, on chilling, three crops of colorless crystals weighing a total of 12.5g (70%) were obtained; m.p. 126-128°C. Samples melting at 116-117°C were also obtained by recrystallization from ethyl acetate. Late samples gave only the higher m.p. The infrared spectra in chloroform of the two samples with different m.p. were identical, with a strong amide CO band at 6.10u.
3-(2-Dimethylaminoethyl)-indole (N,N-Dimethyltryptamine)
JACS 78, 3668-72 (1956)
A suspension of finely-divided amide (2.1g) in 100 ml. of ether was added to a slurry of 0.8 g. of lithium aluminum hydride in 50 ml. of ether, and the mixture was heated under reflux for 4 hr. The mixture was treated in the usual way, and the final organic extract of the amine gave, after recrystallization from hexane, 1.6 g. (85%) of material melting at 47-49°C. This material was converted to a higher melting form (71-73°C) by crystallization from hexane after seeding with an authentic specimen of mp 73-74°C. The infrared spectra in chloroform of the two samples were identical."
...and this finally sounds like a handy-dandy route starting from indole going via tryptophol, provided one has LAH - don't you think? 
i_a |
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IndoleAmine
Dreamreader Deluxe
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| Joined: 09 Feb 2005 |
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18717.10 Points
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seriously - wtf do you want?
Mon Mar 21, 2005 2:26 am |
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I can't see how you think you would/could be of any help with comments like this:
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just because tryptophol is the starting material dosen't meen it is the preparation I had in mind, read what I said couple posts up
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But at least you have become a bit friendlier, nice. Although I don't feel that pointing out/commenting a working synth can be called clogging. And without your help, this thread wouldn't have grown to its actual size and low information content.
But long live the freedom of speech *sigh*
To use your own words: just because I posted about a synthesis starting from the same reagent does NOT mean I did it because it could be the one you meant....
Now dearest sir, would you mind and tell us stoopid poor lower folks what your noble mind has elaborated in your enlightenment?? Else I would say that YOU are a most severe case of a "thead clogger", since the information content of your posts is restricted to linking to distantly related topics and rambling about "OTC via tosylate and with a paint pigment"...
Now come on, you know what I mean - now you can prove that you can do better! 
And we're all not here to play childish "what do I mean"-games; if you have some knowledge that you would like to share, please do it straight away, and if you want to keep it for yourself, the do so - but without such premature and unnecessary secret-keeping please,.
i_a |
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Lief
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| Joined: 16 Feb 2005 |
| Posts: 112 |
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4494.38 Points
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Mon Mar 21, 2005 5:39 am |
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Last edited by Lief on Sat Jun 25, 2005 4:37 am; edited 1 time in total |
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