pHarmacist (Hive Bee)
12-26-02 19:36
No 393175
      Indole-3-Carbonitrile form Indole-3-aldehyde  Bookmark   

Procedures below might give as good pre-cursor for tryptamines as benzylcyanide is for phenetylamines. Please criticizam, bad or good, as long as it's relevant.

Indole-3-aldehyde [1]

Procedure:

In a 1-l. round-bottomed, three-necked flask fitted with an efficient mechanical stirrer, a drying tube containing Drierite, and a 125-ml. dropping funnel is placed 288 ml. (274 g., 3.74 moles) of freshly distilled dimethylformamide (Note 1). The flask and its contents are cooled in an ice-salt bath for about 0.5 hour, and 86 ml. (144 g., 0.94 mole) of freshly distilled phosphorus oxychloride (Note 2) is subsequently added with stirring to the dimethylformamide over a period of 0.5 hour. The pinkish color of the formylation complex may be observed during this step. The 125-ml. dropping funnel is replaced with a 200-ml. dropping funnel, and a solution of 100 g. (0.85 mole) of indole (Note 3) in 100 ml. (95 g., 1.3 moles) of dimethylformamide is added to the yellow solution over a period of 1 hour during which time the temperature should not rise above 10°. Once the solution is well mixed, the dropping funnel is replaced with a thermometer, and the temperature of the viscous solution is brought to 35°. The syrup is stirred efficiently at this temperature for 1 hour, or for 15 minutes longer than is necessary for the clear yellow solution to become an opaque, canary-yellow paste (Note 4). At the end of the reaction period, 300 g. of crushed ice is added to the paste (Note 5) with careful stirring, producing a clear, cherry-red aqueous solution.
This solution is transferred with 100 ml. of water to a 3-l. three-necked flask containing 200 g. of crushed ice and fitted with an efficient mechanical stirrer and a separatory funnel containing a solution of 375 g. (9.4 moles) of sodium hydroxide in 1 l. of water. The aqueous base is added dropwise with stirring until about one-third of it has been added (Note 6). The remaining two-thirds is added rapidly with efficient stirring (Note 7), and the resulting suspension is heated rapidly to the boiling point and allowed to cool to room temperature, after which it is placed in a refrigerator overnight. The precipitate is collected on a filter and resuspended in 1 l. of water. Most of the inorganic material dissolves, and the product is then collected on a filter, washed with three 300-ml. portions of water and air-dried, yielding about 120 g. (97%) of indole-3-aldehyde, m.p. 196–197°. The indole-3-aldehyde resulting from this procedure is sufficiently pure for most purposes, but it may be recrystallized from ethanol if desired (Note 8).


Indole-3-carbonitrile [2]

Procedure

A mixture of 1.44 g. (0.0099 mole) of indole-3-carboxaldehyde,2 7.0 g. (0.053 mole) of diammonium hydrogen phosphate, 30 g. (30 ml., 0.34 mole) of 1-nitropropane, and 10 ml. of glacial acetic acid is refluxed for 12.5 hours. During the reflux period the pale-yellow mixture becomes dark red. The volatile reactants and solvent are removed under reduced pressure, and an excess of water is then added to the dark residue. After a short time, crude indole-3-carbonitrile precipitates rapidly. It is separated by filtration and dried under reduced pressure; weight 1.20–1.34 g. (85–95%). Crystallization from acetone-hexane, with decolorization by activated carbon, yields 0.68–0.89 g. (48–63%) of fairly pure indole-3-carbonitrile, m.p. 179.5–182.5° (Note 1).

Refs:

[1] http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv4p0539

[2] http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?rxntypeid=104&prep=CV5P0656

Hypothesis; a-MT:

[...]

A solution of MeMgI was prepared in the usual manner from methyl iodide (15g, 0.105 mol) and clean Mg turnings (30g) in 200ml dry THF, and the solution was added slowly with good stirring to a cooled solution of (14.2 g, 0.1 mol) Indole-3-Carbonitrile in 150ml dry THF in a dried 1000ml round-bottomed flask. The reaction mixture was stirred at room temp for two hours and then cooled in an ice-bath. The solution was diluted with 150ml of dry methanol and NaBH4 (9.5g, 0.25 mol) was added in portions during 30 minutes, and the reaction mixture was stirred for another hour.

[...]

Ref: ../rhodium/chemistry /amphetamine.html

Do you think that the indolic nitrogen would somehow interfer the reaction described above under -hypothesis-? I can't see why it shouldn't work!

If this has allready been worked out before, please, send me a PM and I'll delete the post..

Regards!


"Turn on, Tune in and Drop Out"
 
 
 
 
    Rhodium
(Chief Bee)
12-29-02 17:19
No 394002
      Indole-3-carbonitrile = Indole-3-CN  Bookmark   

Indole-3-carbonitrile is not the indole version of benzyl cyanide (phenylacetonitrile). Indole-3-carbonitrile is rather an analog of benzonitrile (PhCN). Thus this cannot be used directly for any tryptamine/AMT synthesis.
 
 
 
 
    pHarmacist
(Hive Bee)
12-29-02 17:26
No 394005
      Damn  Bookmark   

How in the hell could I miss that!? It has 1 carbon shorter chain! I was just to excited... Going from the indole-3-acetaldehyde rather than from aldehyde would give desired nitrile, but that's another story.. I got that mixed up that night... :( Thanx for the corection!

"Turn on, Tune in and Drop Out"
 
 
 
 
    Rhodium
(Chief Bee)
12-29-02 18:11
No 394012
      You are not the first  Bookmark   

It's a common error to treat CN- as any other substituent when theorizing about functional group transformations, forgetting that it actually contains a carbon atom.
 
 
 
 
    Barium
(Hive Bee)
12-30-02 03:02
No 394117
      Nitrile formation  Bookmark   

The method you wrote about is a common one-pot method to make aromatic nitriles from aromatic aldehydes. Unfortunately it doesn´t work with aliphatic aldehydes. I´ve been looking at that method for years, with slippery wet eyes just because it is so simple and beautiful.

Catalytic hydrogenation freak
 
 
 
 
    pHarmacist
(Hive Bee)
12-30-02 10:09
No 394210
      Barium  Bookmark   

Here is another procedure that describes preparation of aliphatic nitrile from aliphatic aldehyde, it looks pretty easy and fast to me. Hope you find it as intresting as the above, if the above mentioned relly worked with aliph. that is wink:

Post 392484 (pHarmacist: "Microwave Route to Benzylcyanide", Methods Discourse)

Regards.

"Turn on, Tune in and Drop Out"
 
 
 
 
    Barium
(Hive Bee)
12-31-02 03:11
No 394468
      Yes  Bookmark   

That method works well. I prefer acetic anhydride over pthalic anhydride though. But that´s just a matter of taste I guess.

What I really meant with my previous post was that what I´ve been dreaming for is a one-pot reaction to convert a aromatic aldehyde to a aliphatic nitrile e.g., benzaldehyde to phenylacetonitrile. Wouldn´t that be slick n´ nice smile

Catalytic hydrogenation freak
 
 
 
 
    pHarmacist
(Hive Addict)
12-31-02 04:13
No 394477
      Aha!  Bookmark   

Of course, that would be excellent, aliphatic nitriles are my personal favorites, a one-pot reaction to obtain them from Ar-COH would be a dream come true wink... Oh, no, I've become an Hive Addict frown

"Turn on, Tune in and Drop Out"