Author Topic: good decarboxylation results in DMF  (Read 10776 times)

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Z_Hound

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good decarboxylation results in DMF
« on: March 19, 2002, 12:06:00 PM »
Hello! My first post here,
need feedback on this decasrboxylation/methylation (fictional).

10 g of L-tryptophan (0.05 mol) were mixed with 35 ml of DMF
under argon flow. With vigorous stirring the mixture was brought to reflux
(~155 C) after approximately 20 minutes solution became clear-yellow.
After total 50 min of refluxing, the reaction was stopped;
DMF was removed at  ~10 mm Hg (??) (boiled around 45 C)
Dark - yellow - orange residue was dissolved CH2CL2 (dissolves completely)
resulted solution has dark-orange color.  This was washed in sequence with 2% NH4HCO3
and distilled water, CH2CL2 was dried over sodium sulfate overnight.
solvent was rotor-vaped out, orange-yellow crystalline solid was formed. (m.p. 112 C)
This was recrystallized from hot benzene, yellow-light-orange crystalls m.p. 117 C -  6.9 g ( 86%)

different catalysts in dmf were tried:
With 0.3g of methyl-ethylketone - yeild was only 70%
with 0.2 g of acetone - yeild was only 60%
with 0.5 g of benzyl-methyl ketone - 74% (this is the best keton ever! and ... still not good.)
with 0.5 g of cylcoxenanone -                62%

Seems that in DMF one does not need catalyst.
Also it seems, less product forms if you do it without inert gas flow, or reflux for more than 1.5 hr
(then mixture becomes dark - red; it seems you need to stop it when it is bright-yellow).
------

Methylation attempt:

2 g of tryptamine (~0.012 mol)  is dissolved in 15 mL of MeOH, 5 mL of 38% formaldehyde (~0.06 mol) was added, the mixture was stirred in the argon flow, at room temperature for ~2 hrs.
The mixture was placed in the cold bath (CHCL3/liquid-N2 ~220 K) and 2 g (~0.05 mol) of solid CaH2 was added in small portions. Reaction was left to stir untill all liquid N2 in the bath was gone. Then it was placed in the ice bath and was stirred for 24 more hrs (ice was allowed to melt).
The resulted mixture wasdiluted with large amount of CH2CL2
(100 mL) which was in turn washed with 2% (NH4)2CO3, distilled water; followed by drying over sodium sulfate
for 6 hrs. sodium sulfate was filtered off, CH2CL2 removed on rotor vap;
dark-brown residue was distilled under vacuum with oil pump.  (2 fractions collected)
low-t boiling fraction - 0.7 g (formed yellow crystalls - dimethyl form, ~30% yeild, m.p. 68-70 C)
high-t boiling fraction       was discarded      (seems it was unreacted tryp or monomethyl form)
 ----
I believe that low yeild was the result of the overheat during vacuum distillation.
However, I still have faith in the CaH2 method and will think how to optimize it.
did anyone try : NaH; or just bubble hydrogen through?

-------

Z_hound





Any Possession is a Demonic Possession!

Ritter

  • Guest
CaH2?
« Reply #1 on: March 19, 2002, 08:11:00 PM »
Hello,

I have never heard of CaH2 being used as a reductive amination catalyst.  Do you have a ref for this or is this something you thought of on your own?  If the latter is the case and you really did get active product, CONGRATULATIONS!!

cilliersb

  • Guest
CaH2
« Reply #2 on: March 20, 2002, 02:43:00 AM »
I think the bad yeild can be attributed to water in the reaction mixture during the Dimethylation of your TRP.

I assume you used 38%Aq. Formaldehyde, the water in this solution will definitely react with a big portion of your CaH2 and render it useless.

Try using a rather large excess of Reducing Agent and see if this improves yeilds. (maybe 50% or more)

Was the product tested / bioassayed. If so, please report on your results. This could be the synth of choice for swim if we can boost yeilds to the 50%+ region.

Bee Well ;D

foxy2

  • Guest
Anhydrous formaldehyde
« Reply #3 on: March 20, 2002, 03:45:00 AM »
Anhydrous formaldehyde would probably work better.
Here is what you need.

Patent GB1301533



Foxy


Those who give up essential liberties for temporary safety deserve neither liberty nor safety

Lilienthal

  • Guest
Where are reducing agents?
« Reply #4 on: March 20, 2002, 08:29:00 AM »
Where are the reducing agents? CaH2 and NaH are strong bases but not reducing agents. The second step of your syntheses doesn't make sense to me.
And the boiling point of DMF of 45°C at 10 mm seems a bit low.

Z_Hound

  • Guest
hydrogen
« Reply #5 on: March 20, 2002, 08:52:00 AM »
Apparently, it is hydrogen, which is generated in the mix when a hydrid
reacts with alkohol or water. It is as the same as for NaBH4 or LiALH4, i suppose,
e.g. : NaBH4+MeOH -> MeONa +1/2 H2 + 1/2 B2H6; or just BH3*THF;
BH3+MeOH -> B(OMe)x + H2; borohydrid is pretty strong reductunt, and very often reduces 2,3- double
bond in the indole ring, so, i decided to try something else - CaH2
which is base only in the same sense, as NaBH4 is base (i.e. reacts wiith "acidic" protons)

Any Possession is a Demonic Possession!

Rhodium

  • Guest
DMT bp?
« Reply #6 on: March 20, 2002, 12:28:00 PM »
What was the DMT boiling point, and with how strong a vacuum?

foxy2

  • Guest
comments
« Reply #7 on: March 20, 2002, 05:32:00 PM »
I'll admit my initial reaction was the same as Lili.  I did some searching and CaH2 is used very little in organic chemistry, the only common use is to dechlorinate various chlorine containing aryl and alkyl hydrocarbons.  It has many uses in inoganic chemistry, chiefly as a reducing agent.

Ok now the big question.
Can this work for methylateing tryptamine to DMT?
I think it MIGHT, i'll post some references later.






Those who give up essential liberties for temporary safety deserve neither liberty nor safety

Lilienthal

  • Guest
Reaction mechanism of hydride reduction
« Reply #8 on: March 21, 2002, 07:36:00 AM »
NaBH4 or LiAlH4 don't reduce carbonyls because they can develop hydrogen on reaction with acidic protons  ::) .

The low bp product may be simply formyltryptamine. Have you tried an acid /  base extraction, TLC, or some other tests, to find out if it is an amine?

Z_Hound

  • Guest
Good point.
« Reply #9 on: March 21, 2002, 02:12:00 PM »
Formyl-tryptamine is a possibility.

The product was bioassayed with inconclusive results.
~100 mg in the evaporator on a hot plate. - definetely not
as strong as dmt; or if dmt not as pure as it should be.
Increased heart beat, and slight shake in the surroundings, with "oohooh"
sort of sound - whole thing lasted couple minutes.
--------
I read about methylation with dimethyl-sulfate and K2CO3 somewhere on this forum.
Is there good method of making dimethyl-sulfate from methanol and sulfuric acid?
I browsed web for dimethylsulfate a little, all I learned that it is extremely cancirogenic.
-----
about Al, B hydrides:;
 as far as I understand, the  mechanism as  addition, say to some shiff's base, for example, would be:
RR'C=NR'' + MH ---> RR'CH-N(M)R'' (M- 'metal', Al, or B)
RR'CH-N(M)R' + ROH ---> RR'CH-NH-R'' + ROM
In the case of Al, and B, M-H bond is of rather covalent character;
while in the case of Ca, or Na, it is  ionic. So, in the latter case,
it seems, it rather evolves H2 when reacts with alcohol.
-----
Thanks for the feedback!
-----
Z_hound

Any Possession is a Demonic Possession!

slothrop

  • Guest
reductive alkylation
« Reply #10 on: March 21, 2002, 05:07:00 PM »
Most attempts of reductive alkylation of tryptamine with formaldehyde I've seen has not given that high yields. How about an approach with Ti(iv)isopropoxide and NaBH4 in diglyme? I remember seeing dimethylation done in quite good yields of various amines. Anyone tried it on tryptamine?

//Tyrone Slothrop

Sunlight

  • Guest
Testing your procedure
« Reply #11 on: March 22, 2002, 04:17:00 PM »
Inspired by your post, I've beeing trying the same DMF decarboxylation of glycine to recover methylamine. It seems to work very little, a smell of methylamine appears but there is not a consistent bubbling in the receiveing flask and in one hour the rxn was almost like in the beginning. The addition of a bit of cyclohexanone helped rxn a bit, but not enough.
Forgive me, but I have doubt about your procedure so I've put a bit of tryptophan in DMF, and yes, it works like you say, exactly the same. I won't make the workup this time for this small quantity, but I don't doubt you got really tryptamine if you report that mp. And by the way, it seems for me the best decarboxylation method of tryptophan that has been posted here, including the serious references, 1 hour, very good yields and uses only the easy to get DMF.
Congratulations, and thanks.

Z_Hound

  • Guest
Methylation with tosylate
« Reply #12 on: March 22, 2002, 11:46:00 PM »
Disclaimer: procedure below is *entirely* theoretical.

I. Formulation and principle.
   a) Methyl-tosylate is prepared from tosyl-chloride (chlor-anhydride of para-toluene-sulfonic acid)under basic conditions with sodium-methylate.
   b) ... is added to the solution of tryptamine in dichloromethane, stoichiometrically, 2:1
------------
Actual methylation attempt.

MeO-Na : to 20 ml of freshly distilled MeOH was added several small chunks of sodium metal. - small quantity of white precipitate was formed on the bottom of the beaker.
After the gas evolution stopped, the resulted solution of MeOH/MeONa was placed into an addition funnel with a piece of cotton near the valve (to filter).
Note: handling sodium. Sodium was stored in the xylol; must
be handled with extreme care(!!!) one takes it from the flask with forceps, cuts with a knife  and makes strips out of it with a glass tube. Important is to wash utensils after, with isopropanol first, and only then water. Excess sodium can be thrown into isopropanol for deactivation.

2. Meanwhile:
   In the 2-neck small flask: 2 g of tryptamine is dissolved in ~20 mL of freshly distilled CH2CL2 and is stirred with magnetic stirrer at room temperature under argon flow.

The addition funnel with MeOH/MeONa is attached.

3. To the addition funnel is added 2.5 g solid Tosyl-Cl
and is mixed in with a glass rod.

The whole thing is left to stand like that under urgon flow
for ~0.5 hr. Then addition drop by drop starts on the course of 5 min.

Monitoring with TLC
Personal Note: really need help on TLC with tryptamine derivatives.

Solvent used : MeOH:AcOEt (4:1)  and some, undefined (several drops), quantity of diethyl amine.

Tryptamine Rf here was 0.8 (measured from center of the spot)
On the course of the reaction above
spots with Rf )0.7;0.6 and 0.42 were noticed
0.42 was tentatively ascribed to dmt.
spot that barely moved was attributed to fully methylated
salt.

[How do you develop your TLC for tryptamines? what I did:
drop into iodine-filled closed beaker, then dump into water to make them visible]

Reaction stopped after 3 hrs of stirring at room temperature.
Diluted with large amount of CH2CL2 (70 mL) washed with
water solution of diethyl amine, 4% tetramethylammonium salt, and distilled water.
Dried over sodium sulfate, reduced significantly in volume;

and chromatographed on ~15cmx1cm silicagel (100 mesh) column
(Eluted with MeOH, monitored by TLC)

desired fraction after rotor-vaping solvent formed lightly yellow crystalline solid, ~2 g (~80%).
m.p 56 C (huh ??)

WARNING: POISON: TARGET ORGANS: CNS (Yes!)

addressing Rhodium question: sublimes/melts/ at 60-70 C under ~ 1 mm Hg ( small quantity was wasted on that in the
aldritch-micro-scale boiling point apparatus)
{Do not have Mcleod gauge, will borrow from a friend,
and then will report more precisely)

Z_hound









;)

Any Possession is a Demonic Possession!

Rhodium

  • Guest
DMT bp
« Reply #13 on: March 23, 2002, 12:26:00 AM »
The boiling point is way too low. The bp of DMT freebase is 130-140°C at 0.1 mm/Hg.

Ref:

http://www.erowid.org/library/books_online/tihkal/tihkal06.shtml


Sunlight

  • Guest
Mp not bp
« Reply #14 on: March 23, 2002, 04:55:00 AM »
mp is correct, may be it's better to smoke it to see what happens... But you could make the chlorhydrate and make that mp too.

Student

  • Guest
Product Identification
« Reply #15 on: March 23, 2002, 06:24:00 PM »
In your first post you concluded that the low boiling fraction of product was DMT based on its melting range of 68-70°C. The Merck lists 44.6-46.8°C for DMT. Maybe I've missed something, but that seems like quite a difference, especially since your higher mp suggests greater purity than the sample reported in the Merck. On the other hand, if what you analyzed was impure, recovered tryptamine, the melting range could be depressed below the normal 118°C. For example, the crude tryptamine obtained from decarboxylation in xylene using spearmint oil catalyst had a melting range of 104-105°C. Impurities, unless they are the majority of the sample, tend to lower and broaden the melting range. The bioassay you reported sounds like what would be expected of tryptamine (see TIHKAL).

To reduce the likelihood of misidentifying a product, use an acid-base workup preceeded by treatment with acetic anhydride. Then neither tryptamine nor formyltryptamine would be mistaken for DMT.

I've been surprised how polar tryptamine is on TLC. Even pure isopropanol barely moves it. I would have expected DMT to be less polar, but it is more basic than tryptamine and maybe it is what you have. You seem quite skilled at TLC, even using diethylamine to prevent streaking! Having a reference would make your life easier - perhaps a small extract of one of the plant material rich in your desired product.

If you don't have a nice NMR spectrometer handy, you can always make the picrate derivative and check its melting point (Merck 216-217°C).

Lilienthal

  • Guest
tryptamine + alkylation agent -/-> DMT
« Reply #16 on: March 24, 2002, 01:01:00 AM »
See

Post 126957

(Lilienthal: "Breath of Hoax? / PTC tryptamine alkylation on the test bench", Tryptamine Chemistry)
for a tryptamine alkylation. It's NOT possible to get more than trace amounts of dimethyltryptamine from tryptamine alkylation.

UTFSE to find help about TLC.
I would suggest you to use methanol with an small open vial of conc. ammonium hydroxide in the chamber, alkylamines usually give a front. Use Ehrlich's reagent as a coloring reagent.

Rhodium

  • Guest
tryptamine tlc
« Reply #17 on: March 24, 2002, 01:17:00 AM »
Perhaps a suggestion from 'Hexane' could help you with the TLC solvent system: "On tlc, DET ran just barely faster than DMT (CH2Cl2:EtOH:aq NH3, 40:8:1), which is exactly what I would expect."

Z_Hound

  • Guest
thanks
« Reply #18 on: March 24, 2002, 09:22:00 AM »
thanks for the tips.
Very educating.  Would 4-amino-bezaldehyde work for staining instead?

Z_Hound

Any Possession is a Demonic Possession!

Rhodium

  • Guest
Erlich's reagent
« Reply #19 on: March 24, 2002, 11:48:00 AM »
I only know of 4-(dimethylamino)benzaldehyde plus a lewis acid - Erlich's reagent. It should work all right, and you may find a lot of info on it in THFSE and on google.com.

Here for example:

http://www.erowid.org/plants/mushrooms/mushrooms_article2-2.shtml