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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 6:35 am |
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Last edited by Lief on Sat Jun 25, 2005 4:39 am; edited 1 time in total |
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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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Tue Mar 22, 2005 5:14 am |
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Last edited by Lief on Sat Jun 25, 2005 4:40 am; edited 1 time in total |
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IndoleAmine
Dreamreader Deluxe
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| Joined: 09 Feb 2005 |
| Posts: 681 |
| Location: Bahamas |
18717.10 Points
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Tue Mar 22, 2005 2:30 pm |
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Wow - so then one can methylate trp with CH2O/NaBH4 and GAA, without pictet-spengler cyclization?
No cyanoboro needed anymore? 
...and it would've been nice if anyone had told me THIS before I got attacked for mentioning the mannich rxn and saying that acetaldehyde would lead to tryptamines here....
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Bull. Soc. Chim. Fr., (4)(Pt. 2), 1424-6 (1973)
The Mannich reaction of ClCH2CHO with indoles in the presence of NHR32 gave gramines I (R = H, Me; NR32 = NMe2 morpholino; R3 = H, MeO) which were reduced by NaBH4 to the corresponding tryptamines II. Hydrolysis of I gave the amino alcs. which also rearranged to the a-hydroxytryptamines; dimerization during hydrolysis was also obsd. Treating II with addnl. ClCH2CHO gave tetrahydrocarbolines III (Q = CHCH2X, X = Cl, OH, H, SO2C6H4Me-p) by a Pictet-Spengler condensation. Redn. with NaBH4 gave the azepinoindole III (Q = CH2CH2).
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..found in the Rhodium archive....
The problem with acetaldehyde giving branched alkyl chains is circumvented (although I don't understand how)...
And pictet-spengler avoided through using excess indole.....
The product is a mixture of skatole (probably due to the formation of some side-chained, wrong compound that was depicted earlier in this thread?), and N,N-dimethyl-trp - nothing my column couldn't take care of...
(if I had known just before!  )
i_a
Last edited by IndoleAmine on Tue Mar 22, 2005 2:38 pm; edited 1 time in total |
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IndoleAmine
Dreamreader Deluxe
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| Joined: 09 Feb 2005 |
| Posts: 681 |
| Location: Bahamas |
18717.10 Points
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DMT VIA MANNICH WITH ACETALDEHYDE
Tue Mar 22, 2005 2:31 pm |
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Whole text? - there you are:
| Quote: |
New route to DMT & 5-MeO-DMT
Translation by Chimimanie, HTML by Metanoid
Original French Article: Bull. Soc. Chim. Fr., (4)(Pt. 2), 1424-6 (1973)
--------------------------------------------------------------------------------
[ Back to the Chemistry Archive ]
Abstract
The Mannich reaction of ClCH2CHO with indoles in the presence of NHR32 gave gramines I (R = H, Me; NR32 = NMe2 morpholino; R3 = H, MeO) which were reduced by NaBH4 to the corresponding tryptamines II. Hydrolysis of I gave the amino alcs. which also rearranged to the a-hydroxytryptamines; dimerization during hydrolysis was also obsd. Treating II with addnl. ClCH2CHO gave tetrahydrocarbolines III (Q = CHCH2X, X = Cl, OH, H, SO2C6H4Me-p) by a Pictet-Spengler condensation. Redn. with NaBH4 gave the azepinoindole III (Q = CH2CH2).
Introduction:
The condensation of indole with chloroacetaldehyde and dimethylamine provided the alpha-chloro-methyl-gramine 1a isolated in the form of its chlorhydrate. The base of Mannich 1e of the methoxy-5-indole with chloroacetaldehyde and dimethylamine also has been prepared. The yields vary from 30 to 45%.
An interesting and simple reaction of those chloromethyl-gramines was the reduction in ionizing medium (6, 7). The reduction of the alpha-chloromethyl-gramine 1a by sodium tetrahydroborate in diglyme provided the dimethyl tryptamine (DMT) (yield 37%).
The methyl-1 and methoxy-5 dimethyl tryptamines 2b and 2e have also been prepared.
(...)
Experimental:
alpha-chloro-methyl-gramine 1a, method A
Stir at RT, till dissolution, 2,75g of anhydrous sodium carbonate in a slurry of 50 mL of GAA and 25 mL of propionic acid. Add to this solution 11.7 g of indole (0.1 mol) and 8.8g (0.11mol) of dimethylamine-HCl in 5 mL of diglyme. Cool between -5°C and 0°C and add 11g of chloroacetaldehyde hydrate (containing 75% of the chloroacetaldehyde, 0.1 mol). Stir for 1 hour and keep the temp below 0°C then keep it for 5 days in the freezer at +5°C. Pour the reaction on some piece of ice. A white, snow-like precipitate form. This precipitate (the product of the indolic condensation) is essored. The acid filtrate is extracted with cold ether. The aqueous layer is then energically cooled and ether is added. With stiring this solution is neutralised with some aqueous NaOH. The following operations are then effectued rapidly: decant the ether layer, dry it on Na2SO4, and then with stirring and at low temperature add some hydrochloric ether.
The alpha-chloromethyl-gramine HCl (1a) fall as a viscous oil. The ether is decanted, and the oil is recrystallised with a little absolute EtOH. Add if necessary anhydrous Et2O. The product may have a pink coloration.
Crude yield: 11.7 g (45%), mp=131°C. Recrystallise 3 times in Et2O-EtOH or acetonitrile, final yield: 8.2g (32%), mp=138°C.
N,N-dimethyl tryptamine 2a
1 g of alpha-chloromethyl-gramine HCl is added to a suspension of 2,5 g of NaBH4 in 75 mL of diglyme at 55°C with stirring. The slurry is warmed to 85-90°C and is kept at that temperature for 48h. The yellow coloration has disappeared. After 24h the mixture is cooled and poured on some ice. This is extracted with ethyl acetate and then the solvent is removed. The remaining oil has got a scatole stench and the TLC show two spot with Rf equal respectively to authentic sample of scatole and of DMT. These two products are separated by column chromatography (silice-celite 1/1). The scatole is eluted first with benzene and is identified by its mp and its picrate salt. The DMT is eluted with methanol (270 mg, 37%). After one recrystalisation with hexane, the product melt at 45°C, this mp is inchanged when authentic sample is mixed with it. The DMT is confirmed by its picrate salt, mp 166°C, and by its UV and IR spectra.
5-methoxy-N,N-dimethyl tryptamine
Same procedure. With 1g of the chloromethyl-amino-indole HCl we obtain an oil with only one spot on TLC. The picrate of this indolic base has got a correct analyse on C,H and N. It melt at 176°C. The freebase crystallise and its mp is 69°C. Yield: 28%, the HCl salt has a mp of 146°C.
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i_a |
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wyndowlicker
Member of the Month
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| Joined: 17 Feb 2005 |
| Posts: 41 |
| Location: honeycomb hideout |
877.82 Points
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has anyone tried CDI
Sun Mar 27, 2005 6:02 am |
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Hey now,
I have a question?Will CDI (carbonyldiimidazole)work in this reaction?
W.L |
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Sandmeyer
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| Joined: 25 Mar 2005 |
| Posts: 39 |
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203.32 Points
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Sun Mar 27, 2005 8:23 am |
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| In Tetrahedron Letters 35[38], pp. 3981-3984 1994 there is an example of mesylated tryptofol being swapped with dimethylamine, the yield of DMT is over 70%. |
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IndoleAmine
Dreamreader Deluxe
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| Joined: 09 Feb 2005 |
| Posts: 681 |
| Location: Bahamas |
18717.10 Points
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"swap"
Sat Apr 09, 2005 11:52 am |
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Thanks for the enormous amnt. of knowledge and the abundance of details your post radiates...
(explanation: I think you already said what you just said, although under another username; and back then as well as now you don't provide any details - why not?)
The following is found in a patent Lief was kind enough to provide us with (it can be found in the "wanted references" thread):
"The replacement of hydroxyl in IV (Tryptophol) with dialkylamine to produce V (Dialkyltryptamine) is generally carried out as a two-step reaction in one reaction vessel.
The alcohol IV can be reacted with mesyl chloride, (CF3SO2)2O, and the like, in a dry inert organic solvent, e.g., tetrahydrofuran, dioxane, diethyl ether, 1,2-dimethoxyethane, dichloromethane and the like, at about -30 to -10°C, under a dry N2 atmosphere, in the presence of a proton acceptor, being a soluble alipathic or aromatic amine, e.g. triethylamine, pyridine, diethylmethylamine, diisorpopylethylamine, tributylamine, 4-dimethylaminopyridine, and the like to form the intermediate mesylate or sulfonate, in situ.
The dialkylamine analog V can then be prepared by simply adding the dialkylamine to the mesylate reaction vessel contents, and allowing to stir at room temperature for 1 hour. The obtained structure V can be isolated as is or reacted with an appropriate pharmaceutically acceptable acid, e.g. HCl, H2SO4, benzoic acid(.....)to form the acid addition salt."
i_a
Last edited by IndoleAmine on Mon Apr 11, 2005 7:08 am; edited 1 time in total |
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Star-light
Blacklight bulb
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| Joined: 26 Mar 2005 |
| Posts: 77 |
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2681.50 Points
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Re: "swap"
Sun Apr 10, 2005 4:02 pm |
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| IndoleAmine wrote: |
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Thanks for the enormous amnt. of knowledge and the abundance of details your post radiates...
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Are you making a sarcastic comment to sandmeyer? I hope not, the post is good.
I may be wrong, but I get the feeling that you are criticising him/her because of the comment made in this thread:
https://synthetikal.com/synthforum/viewtopic.php?t=680&postdays=0&postorder=asc&start=0
where he/she pointed out that you could not use formaldehyde in a Reimer-Tiemann formylation.
Whether I am right or not about this, the following still applies:
Although I can see you are putting a lot of work into this site IndoleAmine (and for that you must be thanked), it has to be said that you make a few factual mistakes in your posts and are not very gracious about accepting this when they are pointed out.
Please don't regard this as a personal attack, I am merely trying to make this place better. I'm sure you know lots about the subject in question, but I think you need to be more careful with the exact wording of your posts in order to avoid confusion. I think sometimes your enthusiasm to share your knowledge means that you are tempted to write without thinking, and this leads to factually incorrect information.
In addition when somebody does point out that you have made a confusing statement then it is better to accept it with good grace than to go into defensive mode.
By way of example, when you say:
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make the 2,5-dihydroxybenzaldehyde via "Reimer-Tiemann"-formylation with HCHO"
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you cannot rightly claim
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"I didn't say anything about formaldehyde, just mentioned the term "formylation" - which is adding "-CHO" (= "formyl").....
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when HCHO IS formaldehyde
I think that being a moderator carries with it special responsibility to be sure your posts are properly researched and factually correct. This site will live or die on the quality of its membership, and this in part relies on their respect for the moderators. Being defensive to the extent you are puts this respect in jeapordy.
If you hold it against me for making this post, or become defensive and argumentative, or ignore me completely, then this is a sign that you have not understood it or my intentions.. All of these scenarios are OK though, I'm not going to cry as a result of any of them!
Although this post may be off-topic in this thread (for which I apologise), I feel that it is of importance to the future of this site and needs to be said. In fact it is no more off-topic than the type of arguments about who said what which it is aiming to reduce.
EDIT: However I do sympathise with you to an extent, as sometimes people are not very gracious in the way they point out to you when your post is unclear / factually incorrect. I think the membership expect very few mistakes from moderators (such is the burden of the moderator).
PS: Your energy and enthusiasm are appreciated.
PPS:
| IndoleAmine wrote: |
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(btw "meant" is commonly written with "ea" - not "ment"....)
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Don't you think that arguing over a missing letter is somewhat petty? You don't bother when others do it, so it is just a cheap "point-scoring" exercise - not something you expect from a moderator. |
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IndoleAmine
Dreamreader Deluxe
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| Joined: 09 Feb 2005 |
| Posts: 681 |
| Location: Bahamas |
18717.10 Points
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you're right
Mon Apr 11, 2005 6:45 am |
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You're right in every point, I must admit (besides the reason for my personal dislike for Sandmeyer, see below).
And in this case, since you are so extremely polite, it doesn't matter if it is slightly off-topic, since it is directly related to the preceding posts, and doesn't create a hostile atmosphere at all - two good preconditions for a useful post. Always better than being rude, offending - and strictly 100% to the topic...
Only thing that I can add to my defense is that Sandmeyer already had posted about this ref before, under another name and along with many rude, personal accuses, and was finally banned from this place. Then a huge clean up action took place in this thread, involving deleting all flames. Then he rigistred again, ad was a bit more polite. But since he only posts if I make a mistake in one of my posts, I must admit that don't like him very much (gee, I don't like faultfinders in general).
BTW he didn't correct my little error by saying "its CHCl3 not HCHO", which would've saved us alot of trouble. Java did so, and was NOT attacked by me. Just wanted to mention it...
My "auto-defense mode" stems from the rough hive times, I'm afraid...
But thanks for your encouragement! Nice to see that not all bees are here to exercise as my "personal mood deteriorator"....
Anyway, I'll give my best to be more accurate (and less insultive) in my postings in the future and promise that I'll try to carry my responsibility with a bit more "contentance" from now on..
i_a |
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Sandmeyer
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| Joined: 25 Mar 2005 |
| Posts: 39 |
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203.32 Points
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Mon Apr 11, 2005 6:17 pm |
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| Time has passed since his hive escapades. Fact that he has been given (illusion of) power in form of moderator status adds to the problem, as his behaviour has become much worse now in comparision to the hive-times. |
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Star-light
Blacklight bulb
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| Joined: 26 Mar 2005 |
| Posts: 77 |
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2681.50 Points
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Mon Apr 11, 2005 10:29 pm |
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| IndoleAmine wrote: |
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Anyway, I'll give my best to be more accurate (and less insultive) in my postings in the future and promise that I'll try to carry my responsibility with a bit more "contentance" from now on..
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Well, you have shown an ability to accept criticism in your response, and for that you should be praised. If you try to do these things it will only gain you more respect. Sometimes it is better to curb your enthusiasm than to say something inaccurate. And petty arguments never make anyone look good, so it is best to rise above them.
One thing, I think that difficult as it may be, a moderator should try to exclude their personal likes/dislikes of members from influencing the way in which they respond to posts.
| Sandmeyer wrote: |
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Time has passed since his hive escapades. Fact that he has been given (illusion of) power in form of moderator status adds to the problem, as his behaviour has become much worse now in comparision to the hive-times.
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Whether this is true or not, I think it is only fair to take him at his word above, wipe the slate clean and see how things go from now on. There is no sense in anybody bearing a grudge. |
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