05-19-00 10:13
No 6702
--psyloxy--
(Moderator)
05-22-00 04:21
No 7781
Rhodium: the indolyl-ethyl-bromide route is one of the best routes to dialkylated tryptamines. It is very fast and gives very pure products which usually do not need to be destilled. The educt tryptophol (hydroxy-ethyl-indole) is commercially available.
(Moderator)
05-24-00 10:28
No 8809
(Rated as: excellent)
psyloxy:
The R-NH2 -> ROH reaction proceeds via a diazonium salt which splits off N2 and leaves the terminal (primary) carbenium ion R-(C+)H2. This rearranges partially to the more stable inner (secondary) carbenium ion. Both intermediates are scavenged by H2O or Cl- or they split off H+. So you get a complex mixture of primary and secondary alcohol, primary and secondary chloride, and inner and terminal alkene...
Preferable syntheses of dialkylated tryptamines are the phenylhydrazine / dialkylaminobutyraldehyde route (e.g. Lil. Ref. #53 and #468, see link below) or the tryptophol route (e.g. tryptophol from indolylacetic acid = IAA = heteroauxin with LiAlH4).
Rhodium:
This is what I found about indole-grignard reactions in the worlds most famous references database (http://www.fortunecity.com/westwood/stor
#307: many (1- or 2-substituted) indoles, indole-3-acetic acids from indoles with n-BuLi and ZnCl2. The Zn-grignard further improves the position-3-over-1-selectivity. J. Med. Chem. 39, 5119 1996 R. D. Dillard et al.
#181: catalytic hydrogenation with in sity H2 generation from formic acid (1-azido-3-indolyl-aceton), indole grignard reaction. J. Het. Chem. 25, 469 1988 J. P. Sanchez et al.
#547: 3-allyl-indole from indolyl-MgBr and allyl bromide, yield 70%, 3-indolyl-acetaldehyde, 3-indolylacetone from IAA with 1. Ac2O / NaOAc, yield 49% 2. MeONa, yield 55%. J. Chem. Soc. 3172 1952 J. B. Brown et al.
#405: diethyl-indolylacetamide from indole, MeI, and diethyl chloro-acetamide, yield 63%. Arch. Pharm. 275, 506 1937 R. Wegler et al.
So indole-nitrogen protection is not needed.
(Chief Bee)
05-25-00 08:51
No 9221
(Rated as: excellent)
Topic: DMT from DMF and IAA (indole acetic acid)
Octahedrical
------------
Side Step 1:
Reflux dimethylformamide (DMF) in 6M HCl for at least 6 hours-->
dimethylamine + CO2H and other stuff. Use an acid-base extraction to isolate the
amine product.
Main Step 1:
Indole acetic acid (IAA) + B2H6 (diborane) in THF (tetrahydrofuran) or diglyme
at room temperature--> 3-(2-hydroxyethyl)-indole.
Main Step 2:
3-(2-hydroxyethyl)-indole + PBr3 (phosphorus tribromide)--> 3-(2-bromoethyl)-indole.
Add water. Use a sep funnel and discard the water layer.
Final Step:
3-(2-bromoethyl)-indole + dimethylamine--> dimethyltryptamine (DMT)
Yields will be better than anything else out there. Main Step 1 happens very
quickly at room temperature. Step 2 I've heard is really a breeze (again no
reflux required I don't think). Step three takes a couple of days, but it is at
room temp I think. I'll read up on this some more. No one has ever done this, to
my knowlegde. (Unless they want to come forward.)
----------------------------------------
Teonanacatl
-----------
Synthesis of tryptophols (indole-3-ethanols):
a) Sodium-Alcohol reduction: first chem. synth of tryptophol by Bouveault-Blanc
reduction (Na/EtOH) of methyl or ethyl esters of IAA...yields up to 81%
reported...46% yield from another source [could you react IAA w/
methanol/ethanol (excess, distilling of H2O) to produce the methyl or ethyl
ester and then use a Bouveault-Blanc procedure?... even easier to get hold of
reagents!...if you've got the proper supplies, you could even do a reductive
halogenation with LAH, followed by HBr, ie. IAA-->3-(2-bromoethyl)indole]
b) LAH reduction: first reported 65% yield of tryptophol from IAA...methyl and
ethyl esters of IAA giving over 90% yields...for large scale procedures, it has
been reported that the glyoxyl chloride of indole can be converted to the
glyoxylic acid ester and then reduced w/ LAH to tryptophol...over 85% yield
claimed.
This definately seems a possibility...same ref goes on to say:
Reactions of tryptophols:..."usually used as intermediates for one of the
earliest yet most convenient tryptamine syntheses: phosphorous tribromide in
ether or benzene converts tryptophols into 3-(2-bromoethyl)indoles in good yield
and subsequent reaction with ammonia or amines makes available a wide array of
tryptamines."
The only flaw I see with your procedure is the diborane bit...I've never seen
this used for reduction of carboxylic acids or esters...
ref: "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.
Just found another ref:
"N-disubstituted tryptamines are obtained in high yield on boiling a solution of
tryptophols in benzene or xylene with secondary amines and a nickel catalyst."
V.I. Shvedov, L.B. Altukhova, L.A. Chernyshkova, and A.N. Grinev, J. Org. Chem.
USSR, 5, 2158 (1969).
Anyone want to look this one up?
P.S. Do you think 4-chloro-IAA would survive this same rxn?.. it's another
reasonably common plant hormone... 4-Cl-DMT?
-Teo
----------------------------------------
Know Conscience
---------------
Main Step One:
Diborane is a newer (than LAH), more selective reducing agent specific for
carboxylic acids. It reduces them to primary alcohols quickly and in high yield
at room temperature in an ether solvent such as diglyme or tetrahydrofuran.
LAH will also get the job done, but it is notoriously difficult to work with and
apparently only gives a 65% yield in this instance.
Main Step 2:
Once you've got the 3-(2-hydroxyethyl)-indole made, PBr3 is a better way to
brominate it than HBr. This is because HBr is a stronger acid than PBr3 and will
therefore tend to favor an unwanted dehyration side reaction on this primary
alcohol.
That is,
3-(2-hydroxyethyl)-indole + HBr--> 3-(2-bromoethyl)-indole + 3-styrene-indole.
Also, every one PBr3 molecule has the potential to brominate three
3-(2-hydroxyethyl)-indole molecules to form three 3-(2-bromoethyl)-indole
molecules plus one H3P04 (phosphorus acid) molecule. So if you have X moles of
3-(2-hydroxyethyl)-indole, you will only need to use X/3 moles PBr3.
Phosphorus acid is water soluble and has a high boiling point, so it can
therefore be separated from the brominated indole product by means of an
oil-water separation or by simple distillation.
* * *
The 1969 USSR reference you mention sounds very promising as well, especially
since it would negate the necessity of having a third step in the first place.
4-Cl-IAA can also be used. Since the chlorine of 4-Cl-IAA is attached to an
aromatic portion of the molecule, it is much harder to remove than the bromine
of 3-(2-bromoethyl)-indole--especially if you use the very mild B2H6 followed by
PBr3 followed by dimethylamine (an Sn1 reaction).
In this case you will get, 4-chloro-DMT. 4-Cl-DMT looks pretty damn psychoactive
to me, and could also be converted to psilocin or even 4-methoxy-psilocin!
http://rhodium.lycaeum.org
(Chief Bee)
05-26-00 13:04
No 9737
(Rated as: excellent)
This is the article from J Org Chem USSR, 5, 2158 (1969) mentioned above
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 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.
Preparation of skeletal nickle: http://water-cooler.com/WC/patentviewer/
Perhaps one could use RaneyNi or just powdered/precipitated nickle?
http://rhodium.lycaeum.org
(Moderator)
05-31-00 09:34
No 11809
In the russian paper they used diethylamine and piperidine, not dimethylamine.
J. Am. Chem. Soc. 61,3499 1939 gives the mechanism: the alcohol is catalytically dehydrogenated to the aldehyde, which reacts with the amine to an imine, which is subsequently hydrogenated to the amine. Usually this gives moderate yields and needs high temperatures (very uncool for the low-boiling dimethylamine...).
I have a second ref (JACS from the fifties (?) using a special Ni catalyst) laying around, which I cannot find at the moment...
I would say that the russian paper looks a bit suspicious...
(Official Hive Translator)
09-30-01 08:42
No 218754
(Rated as: excellent)
I asked Garin and - blessed bee his name! - he found and scanned this article for us - it can bee read (in DejaVu format) in Russian at http://chembook.narod.ru/Letters/joch_v5
DejaVu plugin used to bee available for free at http://www.djvu.com/download/index.html, but it isn't for some reason now - i can email one to anyone upon request.
So I'm happy to tell you, bees, that
a) They DO make _explicitly_ DMT w/this method (benzene, 4h, yield 93%! - about the best)
b) This paper doesn't seem a slightest bit suspicious - in fact, it's a well-documented work w/a wide variety of substances tested, with all the data - mp's and such written out. Here's an exert:
"...Usually the transition from alcohols to amines is realized through replacement of the -OH group w/haloid or tosylate. The drawbacks of the said method include: the need for a large xcess of amine, the possibility of quaternary salt formation and generally low yields of the desired product...
We found that secondary amines are conveniently alkylated w/phenethyl-, phenylpropyl- and indolylethyl- alcohols by boiling the equimolar quantities of the said reragents in benzene or xylene for 4 hours. The yields of tertiary amines comprise 83-87%.
... By a known method (through bromide or tosylate), 2-N,N-trimethyltryptamine was obtained at overall yield of 46,5 %, 5-ethoxytryptamine - 30%. Using our method the above amines were prepared from the corresponding tryptophols in 81-98% yield.
An additional advantage is that this rxn doesn't require inert atmosphere, protection from moisture and is generally non-demanding."
A typical synthetic procedure:
[see Rhodium's post]
The yields: DMT (in benzene) - 93%, mp as hydrochloride 221-222 C; 2,N,N-TMT (xylene) - 89%, mp 231-232 C; 2-methyl-DET(xylene) - 81.5%, mp 206-207 C; morpholyltryptamine(xylene) - 91,3%, mp 211-212 C; 2-methylmorpholyltryptamine(xylene) - 98%, mp 248-249 C.
The yields for phenethyl- and phenylpropyl alcohols are 83-86%, w/morpholine and piperidine as the amines.
So... Has anyone found yet a nice way of reducing IAA to tryptophol, or pulled that enigmatic tryptophane yeast reduction?...
Let's make it work!
Antoncho
(Distinctive Doe)
09-30-01 10:16
No 218769
(Rated as: excellent)
w-(Indol-3-yl) alkanol compounds. Takanashi, Hiroshi; Kubo, Masaaki. (Kawaken Fine Chemicals Co., Ltd., Japan). Belg. (1982), 34 pp. (Pat# FR2499987) French Patent
Abstract
The reaction of phenylhydrazines with 2-acyloxy- and 2-alkoxytetrahydrofurans and -tetrahydropyrans in strong acids gave indoles I (R = H, alkyl, aryl, aralkyl; R1 = H, alkyl, aryl, aralkyl, alkoxy, aryloxy, aralkoxy, halo; n = 0, 1; R2 = H, alkyl). Thus, 2-methoxytetrahydrofuran in MeOCH2CH2OH was slowly added to a soln. (123°) of PhNHNH2 × HCl in MeOCH2CH2OH, and the mixt. was stirred at 122-4° to give tryptophol.
EXAMPLE 1
A solution of 2,17 g (15 m moles) of salt hydrochloric acid phénylhydrazine
in 50 ml monométhylether glycol ethylène has been heated all while being agitee. When the
temperature of the solution salt phenylhydrazine atteignit 123 "C, a solution of 1,02 g (10 m
moles) of 2-methoxytetrahydrofurane in 20 ml monomethylether ethylénéglycol was added
to the drop-to-drip to the solution salt phenylhydrazine during a period 30 minutes. The
mixture reaction was mixed during 1 hour while the temperature of the mixture reaction was
maintained to a level understand between 122 and 124 "C. After the reaction was finished,
the mixture reaction was cooled to the ambient temperature. The mixture cooled reaction
was mix with 100 ml water and, next, submitted to two procedures extraction, each time
with 100 ml chloroform. The two extracts in the chloroform were mixed together and the
mixed extract was washed with water until the aqueous phase become neuter. The washed
extract was distilled under reduced pressure to withdraw the chloroform. The fatty brown
residue of resultant distillation was submissive to ure distillation under reduced pressure.
The tryptophol was obtained as left distilled to a temperature understood distillation
between 167 C and 173 C under a pressure of 2 mmhg, in a quantity of 1s32 g that
corresponds to a yield in percent 82%. The resultant tryptophol has a temperature fusion
56 OC
EXAMPLE 9
take procedures for Them that the one decrites in the example 1 were
realized, except that the solution of 2,89 g (20 m moles) of hydrochlorure phénylhydrazine
in 50 ml n-propanol and a so- lution of 1,02 g (10 m moles) 2-methoxytetrahydrofurane in
20 ml n-propanol were submissive to the procedure reaction, and that the resultant
tryptophol was obtained as distilled fraction toBetween 160 and 165 C sousxune pressure
of 0,5 mmhg. The quantity of tryptophol resultant was of 0,84 g corresponding to a yield in
percent 52 X'S and had a point fusion 57 OC.
Do Your Part To Win The War
(Official Hive Translator)
09-30-01 22:24
No 218955
(Rated as: good read)
All DejaVu prograns may now bee downloaded at
http://chembook.narod.ru/Program/DjVuWeb
- the IE/Netscape plugin for viewing DejaVu files.
http://chembook.narod.ru/Program/DjVuSol
allows to convert images to DejaVu formate.
Sorry for offtopic, but let me tell you, DejaVu definitely rules - a 300 pages book weighs 3,2 Mb! This is by far the best of all graphic text formats i know.
Antoncho