Phenylalanine----------->>> Amphetamine

java · Consumer

Soren_Hansen
(Stranger)
09-07-00 23:20
No 49880




PHE---->Amphetamin
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Hello

I am a Danish foodtechnologist-student with a great love for chemistry. I have tried (legally) all the REASONABLE available recipies on the internet concerning PHE--->Amphetamin. (Catalyst, Electrolysis--) I even made some of my own experiments without any luck. I dont know where to look any more, not even my teacher could help me. Am i looking the wrong place or am i just plain stupid/blind. Im¥n close to the conclusion that it cannot be done and that lyceaum is full of crap!!! sorry

You don¥t have to cut it out in stones, just wave a little!

You don¥t have to put it up here on lycaeum you can mail me privat on sorenhansen.c6@forum.dk

Thanks in advance!!!

God cannot have mercy on the enviroment. BUT YOU CAN!!!
Foodtech. S.H. (DK)

hest
(Newbee / Eraser)
09-08-00 10:11
No 50035




Re: PHE---->Amphetamin
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And PHE is ??

CHEM_GUY
(Hive Bee)
09-08-00 12:37
No 50069




Re: PHE---->Amphetamin
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I think you are talking about my idea that possiblely phenylalanine could be converted into amphetamine via a mixed Kolbe electrolysis. You have gotten all the information from either my website or Rhodium's website, correct?

Well, I don't know what to tell you. It was just an idea! I have not tryed it. All the literature suggests that some of the product will be amphetamine, but there is not direct reference to this in a literature that i could find. Maybe it doesn't work....   However, you could still be doing something wrong. Write up what you did and I will look it over and see if you committed any errors..

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KrZ
(Hive Bee)
09-08-00 20:57
No 50230




Re: PHE---->Amphetamin
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You can only do it multistep.

CO2H -> CH2OH -(H2SO4)-> =CH2 -> CH3

Right?

Share the experiments you did?

CHEM_GUY
(Hive Bee)
09-10-00 17:55
No 50680




Re: PHE---->Amphetamin
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I am not an experimentalist. I only do library work...

All my references are listed on the rhodium site as well as on my site. If it doesn't work, I apologize for ever putting the idea into your head, but the references are compelling and I have not reason to beleive that a yield of amphetamine would not result. I do concede that the conversion will not be perfect and that phenylethylamine will be a by-product as well.

I have not recieve any experimental write-ups from this procedure either so I can't tell you that someone has even failed.

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Soren_Hansen
(Stranger)
09-10-00 22:38
No 50769




Re: PHE---->Amphetamin
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Hello again!

Yes!! Phe = l-phenylalanine

I would very much like to share my experiments with you but my technical English is very bad and it would take me 2 years to write.

Yes. I followed Chem_guys instruction/recipi very precisely. (my teacher and I sad down for 2 hours and translated the wise words (no affence, I think its great what you guys are doing). I used 3 batches, but I had a collaps of some glasware in the first experiment so only 2 went through. The final result did crystalize but there was no amph. present
I might have fucked something up (i don¥t think so, butÖ.)
So don¥t you feel guilty Chem_guy!, Im¥n just an unexperienced student

KrZ did you write the article: Dextroamphetamine from catalytic hydrogenation of l-phenylalanine???
In that experiment you place 500g Phe, 1000ml EtOH, 500ml GAA, 50g Pt/C. in the hydrogenator and îprereducedî it for 2 hours. Catalysing for 22 hours and so one--- You end up extracting with 4*200ml of DCM. What is DCM?? Later one you disolve the base in IPA . What is IPA??
Well i did something very like this!! (in 10g scale) I used 3 batches for this experiment and ended up with no amph. in all 3, here i îvariedî the hydrogenation time 20 - 30 - 48 hours (5 - 6 - 7 ATM)
The reason why i failed might depend one I used the wrong chemical to extract with and disolve in (DCM, IPA)!!!!! Or maybe it can¥t be done this way.!!

KrZ!! what do you mean by multistep, can you specify that a little more!!

I was only allowed to buy 100g of Phe >>its illegal in DK<< Fuck!!!!! I decided to run 10g batches
I have got 20g Phe left and i HAVE to succeed WHAT am i going to do, PLEASE give me a hint. I hate starting something i can¥t finish!!!

Bye the way, in the main menu under Natural amphetamine precursors look under l-Phenylalanine, WHY the fÖ does it say SWIM KNOWS SWIM KNOWS!!! What is it SWIM knows???? That it can¥t be done or there is a VERY easy way to do the synthetic so they have to hide it????? I think it¥s the last answer!!! It wouldn¥t surprise me if you don¥t have to use Catalyst or Electrolysis.

God cannot have mercy on the enviroment. BUT YOU CAN!!!
Foodtech. S.H. (DK)

Fatass
(Stranger)
09-11-00 10:19
No 50948




Re: PHE---->Amphetamin
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I don't have the exact reference with me now, but check out the last few issues of
JOC. Sometime this summer (2000) a nice paper was published giving a method for
the conversion of CO2H -> CH3. It so happens then make amphetamine out of
PHE (I hope they have a DEA license for that!). Basically they go CO2H -> CH2OH
-> CH2I -> CH3.

Neat paper.

------------------------------------------------------------------------------------

Fatass
(Stranger)
09-16-00 12:22
No 52683




Re: PHE---->Amphetamin
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Here is that JOC reference:

"Efficient Procedure for the Reduction of a-amino acids to Enantiomerically Pure a-Methylamines"

Quagliato, D.A. et. al., J. Org. Chem, 2000, v.65, 5037-5042

Summary:
R-CO2H -> R-CH2-OH using LiBH4/TMSCl
R-CH2-OH -> R-CH2-I using polymer supported Ph3P + I2
R-CH2-I -> R-CH3 using N-Selectride

Excellent paper, good discussion on the development of the methodology. Their optimizations were carried out with both enantiomers of phenylalanine, and they got no detectable racemization. Not exactly kitchen chemistry, but an interesting read.

---------------------------------------------------------------------------------

Lilienthal
(Moderator)
09-11-00 12:29
No 50982




Re: PHE---->Amphetamin
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IPA = isopropylic alcohol
DCM = dichloromethane
SWIM = someone who is not me
GAA = glacial acetic acid

There is another route from phenylalanine to amphetamine:

The alpha-methylation of imine-protected amino acids under PTC (phase transfer catalysis) conditions and the subsequent decarboxylation.

Look under
Lilienthal's Pharmacological and Chemical References (http://www.fortunecity.com/westwood/storey/116/index.html) for 'PTC imine C-alkylations' (--477 - --487, --510)
and under 'Trp decarboxylation' for amino acid decarboxylations under +/- mild conditions using higher boiling ketones as catalysts (--44, --45). This decarboxylation usually yields a racemic product.

Why don't you want to use the most simple route via condensation of benzaldehyde + nitroethane and subsequent alanate (LiAlH4) reduction?

For a stereoselective route look into Tet. Asym. 4: 1619 (1993)

Lilienthal
(Moderator)
09-12-00 06:17
No 51292




Re: PHE---->Amphetamin
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For the conversion of tryptophan to alpha-methyl-tryptamine look on my page under --42.

I can't find the 'JOC' paper from this year at the moment, but maybe I will find it tomorrow. This reference has also been posted at the Hive (maybe at the old board).

I hope this helps

CHEM_GUY
(Hive Bee)
09-13-00 11:54
No 51725




Re: PHE---->Amphetamin
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Are you suggesting that a decarb. of phenylalanine to phenethylamine, then a magically transform (magically because i don't know how) into the imine (C6H5-CH2CH=NH).

Then the imine reacts and adds a methyl group on the terminal carbon?

How does someone make an amine into an imine?

I might try a grignard route from the imine to the methyl carbon addition:

R-CH=NH (aq) + CH3MgX --> R-CH2(NH2)-CH3 + MgXOH

In the same vein I posted a varition on the commonly used clandestine approach to a Henry condensation, using phenethylnitro instead of benzaldehyde.

C6H5-CH2CH2NO2 + H(C=O)H --> C6H5-CH=C(NO2)-CH3 --{H2}--> C6H5-CH2CH2(NH2)-CH3

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psychokitty
(Stranger)
09-14-00 21:52
No 52300




Re: PHE---->Amphetamin
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Reduce the phenylalanine to the aminoalcohol using sodium borohydride and either sulfuric acid or I2 in tetrahydrofuran. Then find a way to reduce the alcohol. methedrine can even be made through this route because the reduction step also reduces acyl amides. I have references specifically detailing the the reduction of phenylalanine and N-formylphenylalanine to the aminoalcohol and N-methyl-aminoalcohol. Just ask.

No references for the direct reduction of the aminoalcohol to the desired amphetamine, but the established methods of ephedrine reduction should work. Sorry.

--PK

CHEM_GUY
(Hive Bee)
09-15-00 12:29
No 52471




Re: PHE---->Amphetamin
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Only the iodine reduction will work for the alcohol reduction after the reduction of the acid group on phenylalanine to -CH2OH. A Birch reduction only reduces an aromatic and the subsequent results is a esult of decomposition, such as benyl alcohol reduction, benzyl ether cleavage,...

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psychokitty
(Stranger)
09-18-00 12:55
No 53171




Re: PHE---->Amphetamin
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Although interesting, that is not the paper that I was referring to.

The ones I have are as follows:

JOC 1993, 58, 3568-3571 (NaBH4 & I2)
Tetrahedron Letters Vol. 33, No. 38, pp.5517-5518, 1992 (NaBH4 & H2SO4)

Sorry.

--PK

IOC
(Stranger)
03-20-01 05:25
No 179281




Re: PHE---->Amphetamin
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Would there be other methods for reduction of the aminoalcohol other than using sodium borohydride?

java · Consumer

Serious Chemistry

java
(Hive Bee)
06-30-04 20:14
No 516647




Phenylalanine to amphetamine continuation.....
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Continuation of.......Post 49880 (Soren_Hansen: "PHE---->Amphetamin", Serious Chemistry)

Rather than continue on the old thread this will continued the conversation of the long sought after solution to convert Phenylalanine to amphetamine. All through the thread methods to reduce to the alcohol,Phenylalinol, have been discussed and well resolved . Pending has been the final step OH to CH3. It seems that an intermediate step must be made wither through halogenation with thionyl chloride or similar acids or the well known RP/I with some comments made by Rhodium as to longer reaction times and larger equivalents of reactants.

A question comes to mind, since the reduction of the Phenylalanine using the NaBH4 & H2SO4 or I reduces to the alcohol without worrying about protecting the -NH2 then when it comes time to chlorinate with an acid , will the NH2 react with Cl and make an -NHCl , and if so if one would Hydrogenate with Pd , I know the Cl on the carbon will reduce but will this also be true for the clorinated amine?

There must be a way to halogenate the OH or reduce it to CH3 without involving the NH2....I guess I'll keep on looking as I want to avoid the two step protection and de-protection of the NH2......java

Just hold on to the thread...that keeps us going
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Rhodium
(Chief Bee)
06-30-04 22:18
No 516672




It is much simpler - hoffmann alkylation:
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A question comes to mind, since the reduction of the Phenylalanine using the NaBH4 & H2SO4 or I reduces to the alcohol without worrying about protecting the -NH2 then when it comes time to chlorinate with an acid , will the NH2 react with Cl and make an -NHCl , and if so if one would Hydrogenate with Pd , I know the Cl on the carbon will reduce but will this also be true for the clorinated amine?

That is not an issue - the problem is that any molecule containing a primary alkyl halide and a free NH function is extremely dimerization/polymerization-prone - nothing stops the RCH2-X part of one molecule from adding to the HNR'R" of another, irreversibly forming the corresponding alkylated amine RCH2-NR'R".

The Hive - Clandestine Chemists Without Borders

Lilienthal
(Moderator)
07-01-04 04:21
No 516709




... nothing stops it but strongly acidic ...
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... nothing stops it but strongly acidic conditions

java
(Hive Bee)
07-01-04 17:24
No 516800




dimerization/polymerization...
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The suggestion that nothing stops the "dimerization/polymerization" but an acidic environment, hence then is that why the use of RP/I for the conversion of -OH to CH3 works on Phenylalinol? ...see
Post 183266 (Rhodium: "Re: PHE---->Amphetamin", Serious Chemistry)
Post 459611 (Rhodium: "Reduction of Phenylalanine to Phenylalaninol", Stimulants)

But then thionyl acid and many of the Phosphorous acids, which are very acidic, should also work , leaving the -NH2 alone. However the Zn +HCL, also used to chlorinate, has shown to make undesired complex that, it was once suggested it could be avoided by increasing the acid environment.

I've also made a similar inquiry on the cyanuric chloride thread as to the use of a "chemoselective procedure" employin the use ot TCT (2,4,6-trichloro[1,3,5]triazine) complex,..see

Post 450704 (Lego: "Alcohols to chlorides with cyanuric chloride", Novel Discourse)

Post 450765 (Aurelius: "R-Cl from R-OH Org. Lett. (2002)4,4, 553-555", Novel Discourse)

Because the mechanism for the use of TCT or it's complex states.....

.... indicates the occurrance of a type of Sn2 reaction tha may be consistent with the mechanism of Vilsmeier-Haack complex, where the hydroxyl group of the alcohol to form the cationic species, and subsequent neuclophilic attack of halide ion to produce the corresponding halide

.......as stated in Post 450765 (Aurelius: "R-Cl from R-OH Org. Lett. (2002)4,4, 553-555", Novel Discourse)

Just hold on to the thread...that keeps us going
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Organikum
(Wonderful Personality)
07-02-04 02:32
No 516916




For the reduction of the phenylalaninol to the
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For the reduction of the phenylalaninol to the amphetamine I would suggest either to brominate first using PBr3 which can be formed in-situ followed by a catalytic hydrogenation with Pd/C, anhydrous conditions and GAA as solvent. Bromination is told to have advantages over chlorination for making a better leaving group and proceeding more smoothly overall.

Or to iodinate with PI3 - also formed in-situ - followed by reduction with HI. Iodination under anhydrous conditions then adding some 57% HI will get the final reduction going. GAA or H3PO4 as solvent. This will allow far milder conditions than a usual HI reduction and the amino-group will stay untouched for sure.

The perfect solvent would be trifluoroacetic acid. But thats really not cheap and not easy to get.

ORG
I admire your persistance on this Java.

Schnabufugl!

java
(Hive Bee)
07-03-04 18:48
No 517271




-OH to -CH3 and how to get there.....
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Organikum.. it would be interesting to try your suggestion on the halogination method.

...."A proven way from CH2OH to CH3 is chlorination with SOCl2 (or other halogenation method) and reduction with LAH. It should be possible to reduce the alcohol with HI/RP too, but as the alcohol isn't benzylic, it might require a little more work than ephedrine reduction"

. ...............as read here Post 183266 (Rhodium: "Re: PHE---->Amphetamin", Serious Chemistry)

where thionylchloride acid is used , I imagine methanol would be good solvent to hydrogenate using 10% Pd and the final product would be amphetamine hydrochloride, something that appeals to me more and I wont have to gas, which is not the case if I were to use Iodine or Bromide as my halogen. Another reason is the solvents used are pretty much over the counter , methanol, but I must replace thionyl chloride as supplies are limited ....... java

Just hold on to the thread...that keeps us going
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psyloxy
(Hive Addict)
07-03-04 19:31
No 517282




Re: It should be possible to reduce the ...
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It should be possible to reduce the alcohol with HI/RP too, but as the alcohol isn't benzylic, it might require a little more work than ephedrine reduction"

If I'm not completely mistaken there was a patent that described the production of amphetamine by rP/I2 reduction of 1-phenyl-2-amino-1,3-propandiol (not IUPAC name, but you know what I mean...)

--psyloxy--

psyloxy
(Hive Addict)
07-10-04 13:08
No 518572




amines to nitriles w/K2S2O8,cat.NiSO4 84-97%
(Rated as: excellent)
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I know this is a bit off the general line of thought persued here, but it starts with PHE and ends with amph / ---- nonetheless. NaBH4/LiAlH4 or chlorinating agents are not needed here. Everything is really quite OTC.

Decarboxylation of phenylalanine to phenethylamine
Chem. Lett. 893 (1986) (https://www.rhodium.ws/chemistry/trp.decarbox.enone.html) 85% yield.
Post 370959 (Chromic: "Trp decarboxylation", Tryptamine Chemistry) decarb. of various amino acids w/ persulfate & cat. Ag
https://www.rhodium.ws/chemistry/decarboxpha.html PHE decarb. application by Ritter
https://www.rhodium.ws/chemistry/tryptophan.html tryptophan decarboxylation doc

Phenethylamine is easily oxidised to benzyl cyanide in 97% yield, see article below.
Benzyl cyanide is turned into P2P using NaOEt/AcOEt, read a recent success story here: Post 513580 (tetraedr: "Practical P2P synthesis from Bz-CN via Bz(COMe)CN", Novel Discourse).

Well, yeah, from there on I think you know the way home

Bull.Chem.Soc.Jpn., 63,1.1990;301-303

Nickel-Catalyzed Oxidation of Benzylamine with K2S2O8
Aquaeous solution of 0.040 mol/L NiSO4 (0.5 mL, 0.020 mmol) was added to the stirring mixture of benzylamine (0.429 g, 4.00 mmol)in DCM (10 mL) and aquaeous solution (50 mL) of K2S2O8/NaOH (2.7 g, 10 mmol/0.80 g, 20 mmol). Fine black precipitates of nickel peroxide was formed immediately upon addition of NiSO4. The resulted mixture was stirred vigorously at room temperature. After stirring for 6 h, the mixture was passed through a short Celite column to remove the black precipitates of nickel peroxide. The filtrate was extracted with DCM (10 mL X 2) The combined extracts were dried over anhydrous sodium sulfate and evaporated under reduced pressure. The oily residue was purified by silica-gel column chromatography (DCM as eluent) to give benzonitrile (0.384 g, 93%) The amines sited in Table 1 were oxidised in the same manner as mentioned above.

--psyloxy--

psyloxy
(Hive Addict)
07-10-04 23:17
No 518656




one step shorter
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As it turns out, phenylalanine can also be converted to benzyl cyanide directly:

Syn.Lett.; EN; 4; 2003; 542 - 546 - NBS, ammonium chloride, DMF
J.Amer.Chem.Soc.; EN; 106; 20; 1984; 6075-6076 electrooxidation 80% yield <__ could be interesting OTC-wise
Indian J.Chem.Sect.A; EN; 19; 4; 1980; 325-329. CAT
J.Indian Chem.Soc.; EN; 69; 10; 1992; 642-647 dichloramine-B, perchloric acid
J.Chem.Soc.Perkin Trans.2; EN; 1983; 323-334. chloramine-T
Synthesis; EN; 5; 1996; 600-602.CuBr2 t-BuOLi, 53% yield
J.Chem.Sect.A; EN; 27; 1; 1988; 39-43. chloramine-T, perchloric acid

--psyloxy--

demorol
(Hive Bee)
07-11-04 07:33
No 518687




Here are two articles mentioned by psyloxy in...
(Rated as: excellent)
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Here are two articles mentioned by psyloxy in the above post.

One-pot Sequence for the Decarboxylation of alpha-Amino Acids
Gilles Laval, Bernard T. Golding
Synlett 2003, 542-546

Abstract
Treatment of an alpha-amino acid with N-bromosuccinimide in water at pH 5 or in an alcoholic-aqueous ammonium chloride mixture, followed by addition of nickel(II) chloride and sodium borohydride, effected an overall decarboxylation via an intermediate nitrile to afford the corresponding amine in good yield.

Typical procedures

[1] l-Asparagine (2.90g, 19.3 mmol) was taken up in a pH 5 phosphate buffer (prepared from 100 mL of a 0.1 M solution of citric acid and 100 mL of a 0.2 M solution of disodium hydrogen orthophosphate dodecahydrate) (90 mL). To the stirred amino acid solution was added NBS (10.3g, 57.9 mmol) in DMF (20 mL) at r.t., where upon CO2 gas was evolved immediately. After 30 min, nickel(II) dichloride hexahydrate (22.9g, 96.5 mmol) was dissolved into the reaction mixture and NaBH4 (5.84g, 154 mmol) was added in portions with vigorous stirring. Addition of the latter was exothermic and hydrogen gas was vigorously evolved. After 20 min at r.t., the reaction mixture was filtered through CeliteÆ and diluted with distilled water (500 mL). The light green filtrate was loaded on a column (25 cm ? 2 cm) of Dowex 50WX8-200 ion exchange resin, the column was washed well with water (400 mL) and the amine was eluted with a concentration gradient of ammonium hydroxide. Removal of the solvent under reduced pressure afforded the amine, which was treated with 1.0 M HCl to give 3-aminopropionamide (12) as its hydrochloride (1.68 g, 13.5 mmol).

[2] l-Phenylalanine (400mg, 2.42 mmol) was taken up in a mixture of EtOH (40 mL), water (2 mL) and a sat. aq solution of NH4Cl (1.5 mL). To the stirred amino acid solution was added NBS (1.07g, 6.05 mmol) in DMF (5 mL) at r.t., whereupon CO2 was evolved immediately. After 20 min, nickel(II) dichloride hexahydrate (2.30g, 9.68 mmol) was dissolved into the reaction mixture and NaBH4 (915mg, 24.2 mmol) was added in portions with vigorous stirring. Addition of the latter was exothermic and hydrogen was vigorously evolved. After 30 min at r.t., the reaction was filtered through CeliteÆ, and the ethanol was removed. The liquid residue was taken up in water (20 mL) and basified to pH 10 with aq 1.0 M NaOH. The aqueous solution was extracted with ether (2 ? 30 mL). The combined organic extracts were washed with a sat. aq solution of NaHCO3 (20 mL) and dried over MgSO4. Removal of the solvent afforded 2-phenylethylamine (9a) (208mg, 71%) as a colourless oil.

Full text:

Oxidative Decarboxylation of alpha-Amino and alpha-Hydroxy Acids Using Copper(II) Bromide-Lithium tert-Butoxide
Takeshi Takeda, Satoshi Yamauchi, Tooru Fujiwara
Synthesis 2003, 600-602

Abstract
alpha-Monoaklyl alpha-amino acids were oxidized to the corresponding alkanenitriles in good yields by treatment with copper(II) bromide-lithium tert-butoxide. The oxidation of alpha,alpha-disubstituted alpha-amino and alpha-hydroxy acids also gave the corresponding ketones.

Full text:

java
(Hive Bee)
07-11-04 15:07
No 518724




Phenylalanine to amphetamine continuation.....
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Which way to go.......after getting to the alcohol of Phenylalanine, which can be difficult if one hasn't access to THF. The thought of acylating the functional groups of Phenylalanine , has occurred to me via Dakin West Post 385634 (java: "Re: Dakin-West reaction", Stimulants), but it too has its pitfalls , as how to reduce the ketone to and avoiding the extra carbon. * Not to forget the cyanuric chloride and DMT-MM Post 430441 (Lego: "Reduction of carboxylic acids to aldehydes", Novel Discourse)method to make the alcohol , save the chromatography that is require to isolate the product, too much work, although cyanuric chloride is cheap.

Then the thought of methylating the spare H in the alpha position of phenylalanine has already been discussed and several neat ways to do this but again with it's own amount of work. Degradation of Phenylalanine to Phenethylamine for which Psloxy posted....Post 518572 (psyloxy: "amines to nitriles w/K2S2O8,cat.NiSO4 84-97%", Serious Chemistry) and thus provided additonal methods to follow that lead us to P2P ....and home.

Staying with the thought of reducing the Phenyalinol ( the alcohol of Phenyalanine), once one gets some THF or makes it , the idea of refluxing in H2SO4 and heating to dehydrate the alcohol to an alkene, as per any organic chem text, which can then be hydrogenated with Pd to the amphetamine. As mentioned before an acidic environment Post 516709 (Lilienthal: "... nothing stops it but strongly acidic ...", Serious Chemistry) will prevent the amine into going to dimerization/polymerization..Post 516672 (Rhodium: "It is much simpler - hoffmann alkylation:", Serious Chemistry)

To this project it seems worth looking at the dehydration of Phenylalinol , even though re-arrangement can occur or even conversion to ethers. If the alcohol can be evaporated , vapor phase elimination over Al2 O3 is and excellent method since side reactions are greatly reduced( Ref, March 5th ed Pg 1327). but then regardless where the double bond lands it can be removed with the Pd hydrogenation......and so the search continues.....java

Note : *edited by java

Just hold on to the thread...that keeps us going
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psyloxy
(Hive Addict)
07-13-04 22:55
No 519297




more uploads
(Rated as: good read)
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I hope one of you can make sense of these, I couldn't. If there's no general procedure in the experimental section I'm always brutally reminded of not beeing a chemistry student. I'm out to fetch some other intersting articles concerning oxidative decarboxylation of amino acids though.

Z.Phys.Chem. 256,6.1975;880-884
Kinetics of Oxidative Decarboxylation of Some Amino Acids by Peroxy Disulphate Catalysed by Ag+ Ions

Indian J.Chem.Sect.A,27,1.1988;39-43
Role of Chloride Ion in Kinetics & Mechanism of Oxidation of Amino Acids by Chloramine-T in Perchloric Acid Medium

Indian J.Chem.Sect.A,19,4.1980;325-329
Kinetics & Mechanism of Oxidation of Alanine & Phenylalanine by Chloramine-T in Acid Medium

J.Chem.Soc.Perkin Trans.2,1983;323-334
Chloraminometric Reactions: Kinetics and Mechanisms of Oxidations of Amino-acids by Sodium N-Chlorotoluene-p-sulphonamide in Acid and Alkaline Media

J.Indian Chem.Soc., 69,10.1992;642-647
Kinetics and Mechanism of Oxidation of Amino Acids by Dichloramine-B

--psyloxy--

Vitus_Verdegast
(Hive Addict)
07-14-04 10:21
No 519386




Interesting
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Can you get ref 5 & 7 from the first article, concerning Strecker degradation using Ag+ and oxone? It might be interesting for tryptophan --> indole-3-acetaldehyde..

J. Chem. Soc (C) (1966) p 1388
Z. Phys. Chem. (Leipzig) 256 (1975) p 875

http://www.mindspring.com/~rathcoombe/horror/raven2.jpg

psyloxy
(Hive Addict)
07-14-04 13:10
No 519411




the practical articles
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Pol.J.Chem.,55,7/8.1981;1519-1526

4-hydroxy-5(3¥-cyanopropyl)-2-pyrrolidone ( Cool

:

A sample of 0.5g (0.23 mmole) of 4-hydroxy-5(4¥-amino-4¥-carboxybutyl)-2-pyrrolidone was dissolved in 10 mL of 2M citric buffer (pH 4.7) and 2.1 mL of 10% aqueous solution of chloramine-T (4 mole per 1 mole of aminoacid) was added. The mixture was heated in a water bath at 40?C for 10 min. and then 0.1 g of alanine was added to decompose chloramine-T excess. After 10 min the mixture was alkalized to pH 8 with sodium bicarbonate and the product was extracted with n-butanol (2x20mL). The solvent was evaporated under reduced pressure and crude product was purified by column chromatography (Kieselgel 60 MN, Merck, 18g) in the solvent system: EtOAc-MeOH-H2O (5:1:0.75 v/v). The collected fractions were evaporated under reduced pressure and the product was dried under vacuum over P2O5. The yield of 8 was 90%.

Biochem.J.,10.1916;321

Leucine. The synthetic amino-acid (3.6 g) was gently warmed with a solution of sodio-p-toluenesulphochloroamide (13 g) in 100 mL water and the mixture was then distilled. The oily layer consisting largely of isobutyl cyanide was separated and shaken with sodium bisulphite solution to remove a little isovaleric aldehyde. The cyanide was taken up in a little ether and distilled from a small distilling flask. 1.8g of isobutyl cyanide were obtained corresponding to a yield of about 70%.

alpha-amino-phenylacetic acid This was oxidised with two molecular proportions of the sulphochloroamide in the same fashion as in the preceeding experiment with leucine. The oily distillate consisting of cyanobenzene mixed with some benzaldehyde was dissolved in a little ether, shaken vigorously with sodium bisulphite to remove benzaldehyde and then the ether layer washed successively with sodium carbonate solution and water. On evaporation of the ether a 60% yield of crude cyanobenzene was obtained.

j.amer.chem.soc., 106,20.1984;6075-6076

In a typical procedure, a solution of octylamine (517 mg, 4 mmol) in methanol (30 mL) containing NaBr (618 mg, 6 mmol) was placed in a cell equipped qith a carbon rod cathode (8 mm dia.) and a platinum anode (2x2 cm). The distance between two electrodes was 3 mm and no diaphragm was used. A constant current (0.3 A, 75 mA/cm?, terminal voltage 5-7 V) was passed through the cell at about 10?C with external cooling. After 8.6 F/mol of electricity was passed, the yield (95%) of heptyl cyanide was determined by GLC method. Then, solvent was evaporated in vacuo at room temperature, and the residue was poured into water. The product, heptyl cyanide was extracted with CH2Cl2 and isolated by bulb-to-bulb distillation (400mg, 3.20 mmol, 80%).

The electrooxidation of phenylalanine under our reaction conditions gave phenylacetonitrile (80%). 30mL MeOH, 6 mmol NaBr, 4 mmol PHE, 5.7 F/mol.

Yet another protocol for the preparation of alpha-phenylacetoacetonitrile (for what it's worth)

Chem.Pharm.Bull. 9.1961;920

General procedure for synthesis of acetylarylacetonitriles:

To a solution of 8.5g Na dissolved in 85mL of EtOH, a mixture of 1.25 mole of arylacetonitrile and 32g of AcOEt was added, the solution refluxed for 5 h, and poured into ice water. The separated oil was extracted with Et2O, the Et2O layer was washed with dil. NaHCO3 solution and H2O, and dried over Na2SO4. After removal of Et2O, the residue was crystallized from petr. benzine. alpha-phenylacetoacetonitrile: mp: 87 - 88? C ;; N content: calculated: 8.81%, found: 9.05%. No yield is given.

--psyloxy--

java
(Hive Bee)
07-15-04 10:41
No 519592




regarding phenylalaninol....
Bookmark Reply

I have a question that puzzles me, regarding the change in isomer status while doing the reduction of Phenylalanine. Is there a change in the status of L-phenylalanine in conversion to it's alcohol? then if the answer is yes , does it remain the same rotation after it's reduction to CH3? Case in point.....say one starts with d-phenylalninol and once reduced either by thionyl and Hydrogenation with Pd or RP/I will the end product be D-amphetamine or will it change rotation......confused.....java

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Nicodem
(Hive Bee)
07-15-04 10:54
No 519595




Probably not
Bookmark Reply

Unless very basic conditions (LiAlH4 for example) and heat are used in any of the steps where you still have a carbony group intact (COOH or COOR) there should bee no racemisation at all. But even if, the racemization should bee very minimal since the carboxylic group don't allow much enolization (unlike when you have alpha-substituted ketones or aldehydes which recemize readily in basic conditions or heat). The reduction aldehyde intermediate might racemize a little but it gets reduced too rapidly for that to bee of concern.

ìThe real drug-problem is that we need more and better drugs.î ñ J. Ott

Lego
(Hive Bee)
07-15-04 12:18
No 519606




Stereochemistry
Bookmark Reply

L-Phenylalanine is (2S)-2-amino-3-phenylpropanoic acid

Molecule: L-Phe ("C([C@H](Cc1ccccc1)N)(=O)O")

d-Amphetamine is (1S)-1-methyl-2-phenylethylamine

Molecule: d-amphetamine ("C[C@@H](Cc1ccccc1)N")

But if you reduce the carboxylic acid to the hydrocarbon the whole stereochemistry changes, the S form becomes the R form because the priority of the termincal carbon atom changes (dont' ask).

So it is quite useless to reduce natural occuring L-phenylalanine to amphetamine without racemization because you will get the weaker R-stereoisomer (at least according to J. Med. Chem., 1986, 29, 2009-2015, Post 443143 (Rhodium: "TCBOE is in error - again.", Serious Chemistry)).

There is no connection between D/L respectively R/S and the optical rotation (d/l)!

The tendency is to push it as far as you can

java
(Hive Bee)
07-15-04 13:31
No 519617




Stereo isomerization question on Phenylaninol.....
Bookmark Reply

Thank you for the clarificationNicodem and also the illustrated explanation Lego,

So then to start with the alcohol of Phenylalanine..............

D-Phenylalaninol / R-(+)-2-Amino-3-phenyl-1-proanol

would not be a mistake , since the other only option would be the alcohol L-Phenylalaninol / S-(-)-2-Amino-3-phenyl-1-proanol, hence the correct stereo isomer to end with d-amphetamine ( (1S)-1-methyl-2-phenylethylamine ) would be D-Phenylalaninol / R-(+)-2-Amino-3-phenyl-1-proanol....................java

Just hold on to the thread...that keeps us going
http://www.chiapaslink.ukgateway.net/

java
(Hive Bee)
07-24-04 15:14
No 521386




Solubility of Phenylaninol Inquiry...
Bookmark Reply

I haven't been able to find the solubility of Phenylaninol (R-(+)-2-Amino-3-phenyl-1-proanol), as I want to chlorinate it with thionyl chloride and finish it with hydrogenation using Pd catalyst 10%.

Water is out of the question because of thionyl violent reaction to water , hence I need something that will put the alcohol in solution so it can react with the acid.

I thought of using chloroform, as I've used this in the reduction of ephedrine and pseudoephedrine to a chloroephedrine, but not sure that the alcohol will work in this solvent. I guess I will try a small sample for solubility.

....It's just that's been a hazzle just to get Phenylaninol, the alcohol of Phenylalanine, and I don't want to waste it using the wrong solvent......java(

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Rhodium
(Chief Bee)
07-24-04 17:11
No 521414




Note the formation of HCl salts in the reaction
Bookmark Reply

Chloroform is usually a good solvent for aminoalcohols, as well as many of their HCl salts, something which is desirable in this case - as one molecule of HCl is formed for each alcohol function chlorinated, both the product chloroamine and the unreacted amino alcohol will be present as a mixture of their freebases and hydrochloride salts.

RCH(NH2)CH2OH + SOCl2 -> RCH(NH2)CH2Cl?HCl + SO2

If phenylalaninol hydrochloride is insoluble in the reaction solvent, it will precipitate out and may be hard to chlorinate fully using mild conditions - in that case DMF is the solvent of choice.

The Hive - Clandestine Chemists Without Borders

java
(Hive Bee)
07-27-04 13:15
No 522028




Another route to Phenylalaninol.....
(Rated as: good read)
Bookmark Reply

A concise synthesis of (R)-(+)-phenylalaninol from (1S, 2S)-(+)-thiomicamine
Maria D. Rozwadowska
Tetrahedron: Asymmetry, 9(9), 1615-1618 (1998)

Abstract

   (R)-(+)-Phenylalaninol 6 was obtained from oxazolines 3 and 4 derived from (1S,2S)-2-amino-1-aryl-1,3-propanediols 1 and 2 by the action of Raney nickel followed by hydrolysis of the intermediate benzamide 5

Note: Thanks to Azole for aquiring the article for me as noted in Post 521972 (not existing)

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lugh
(Moderator)
07-30-04 21:24
No 522829




Old HCA Article
Bookmark Reply

This old article, Karrer HCA 31, 1617 (1948); should bee of interest because in it phenylalanine is estrified with ethanol and then reduced with LAH

Chemistry is our Covalent Bond

java
(Hive Bee)
07-31-04 17:45
No 522980




More about Phenylalanine....
Bookmark Reply

Lugh thank you for the study, I wasn't able to understand much of it, german is not my language of understanding, but while on the subject of reducing the COOH in Phenylalanine, recently after going over some of the studies made available Post 460118 (Rhodium: "Enhancing NaBH4 Reactivity & Selectivity", Novel Discourse) I noticed a very interesting point made , ......

The N-acyl amino acids give the corresponding N-alkyl
amino alcohols under these conditions (Eq. (32))

R-CH(NHCOR')-COOH-->NaBH4/I2, THF, heat--KOH/MeOH-->

R-CH(NHCH2R')-CH2-OH

R=CH2Ph,R'=H 73%
R=CH2Ph,R'=Me 83%

therefore it seems to me it's best to acylate the amino group before the reduction with NaBH4/I2 in THF then, one would get after reducing the alkyl amino alcohol, methedrine as oppose to plain amphetamine.

I wonder if NaBH4 would reduce the alkyl amino alcohol to an alkane in one step......need to look that up..unfortunately this (https://www.rhodium.ws/djvu/nutaitis.djvu)

Reduction of Monobenzylic Alcohols With Sodium Borohydride/Trifluoroacetic Acid
CF Nutaitis, JE Bernardo.

will not work with our non- benzylic alcohol, however there is someway out there......java

Just hold on to the thread...that keeps us going
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java
(Hive Bee)
07-31-04 20:32
No 523004




Hydrogenolysis of Phenylalaninol.....
(Rated as: excellent)
Bookmark Reply

In mining through the large archives here at the hive I read Post 108597 (dormouse: "drone's amphetamine synthesis contest -drone 342", Novel Discourse) from which psychokitty contributes to the amphetamine contest where she introduces her way to methedrine starting with Phenylalanine .....anyway read it yourself but the point is a reference which she gives ,
Hydrogenolysis of Diaryl and Aryl Alkyl Ketones and Carbinols by sodium Borohydride and anhydrous Aluminum(III) chloride

AoiOno, Nobuko Suzuki, Junko Kamimura

for which deals with the reduction, to the respective Hydrocarbons, of Phenylalaninol alcohols but it also works for the benzylic alcohols in ephedrine and Pseudoephedrine and phenylpropanolamine. One thing also she discusses the acylation of the amine prior to reduction to the alcohol in order to obtain at the end methedrine. Thank you psychokitty for your research........java

Just hold on to the thread...that keeps us going
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java
(Hive Bee)
08-01-04 15:18
No 523116




Syntheses of amino alcohols.....
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Syntheses of Amino Alcohols and Chiral C2-Symmetric Bisoxazolines
Derived from O-Alkylated R-4-Hydroxyphenylglycine and S-Tyrosine

Vesna ^aplar,a,* Zlata Raza,b Darinka Kataleni},a and Mladen @ini}a

CROATICA CHEMICA ACTA CCACAA 76 (1) 23-36 (2003)
ISSN-0011-1643
CCA-2849

Abstract

Chiral C2-symmetric bisoxazolines 1bñf and 2b,c, derived from 4í-O-alkylated R-4-hydroxyphenylglycine or S-tyrosine, were prepared. As intermediates, a series of chiral amino alcohols
possessing substituted phenolic groups was prepared and fully characterized.

CONCLUSION
Chiral amino alcohols with free and substituted (alkyl,benzyl) phenolic groups have been prepared in high yields, using easily available reagents and mild conditions. They served as precursors for the preparation of either macrocyclic or acyclic chiral C2-symmetric bisoxazolines, designed
as ligands for metal-catalyzed enantioselective transformations.

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josef_k
(Hive Bee)
08-02-04 07:33
No 523222




Re: for which deals with the reduction, to the
Bookmark Reply

for which deals with the reduction, to the respective Hydrocarbons, of Phenylalaninol alcohols but it also works for the benzylic alcohols in ephedrine and Pseudoephedrine and phenylpropanolamine. One thing also she discusses the acylation of the amine prior to reduction to the alcohol in order to obtain at the end methedrine. Thank you psychokitty for your research........java

I wonder if it really works with ephedrine and related compounds. The article says they think the reduction works by first reducing the ketone to the benzylic alcohol, which is then dehydrated to the alkene, which is then further reduced to the alkane. But in the case of ephedrine the doublebond may migrate to make an imine, which could be hydrolized if you're unlucky. (See https://www.rhodium.ws/chemistry/phenylacetone.html--ephedrine)
But who knows if it will work until someone has tried it.

java
(Hive Bee)
08-02-04 11:46
No 523245




Hydrogenolysis......
Bookmark Reply

.....but in the case of ephedrine the doublebond may migrate to make an imine, which could be hydrolized if you're unlucky

josef_k At most the activity in the hydrogenolysis would be around the -OH making it an easier leaving group for the catalyst action of NaBH4 , however I don't see how it would revert to a double bond intermediate to reduce to its hydrocarbon.....unless you think there may be some activity with the methylamine group for which I doubt . The main activity with the Aluminum would be with the O.........java

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armageddon
(Hive Bee)
08-05-04 20:36
No 523910




Pd/C and solvents
Bookmark Reply

Java: Water is out of the question because of thionyl violent reaction to water , hence I need something that will put the alcohol in solution so it can react with the acid.

I thought of using chloroform, as I've used this in the reduction of ephedrine and pseudoephedrine to a chloroephedrine, but not sure that the alcohol will work in this solvent. I guess I will try a small sample for solubility.

For dehalogenations, DCM and chloroform are a good choice - but for hydrogenations, alcohols (maybe with additional acetic acid) are the solvents to be used with Pd/C...

http://www.strem.com/code/degussakit.html

Greetz A

Pleased to meet you hope you get my name.
But whats puzzlin you is the nature of my game!

java
(Hive Addict)
08-13-04 19:20
No 525336




Alpha-methyl-Aminoacids .....
Bookmark Reply

Noted in the post listed under Chapter 3 "Ligans for Asymmetric Catalysed Cross Coupling Reactions"

Post 525324 (java: "ENANTIOSELECTIVE CROSS COUPLING REACTIONS", Chemistry Discourse)

......alpha-Methyl-amino acids are now accessible in enantiomerically enriched form via an enzymatic process, developed at DSMResearch Geleen.*8

Ref.
8. a) Kamphuis, J.; Boesten, W.H.J.; Broxterman, Q.B.; Hermes, H.F.M.; van Balken, J.A.M.; Meijer, E.M.;
Schoemaker, H.E. New Developments in the Chemo-Enzymatic Production of Amino Acids in Advances in
Biochemical Engineering/Biotechnology, Fiechter, A. Ed., Springer Verlag, Berlin Heidelberg, 1990, and references
cited therein. b) Kaptein, B.; Boesten, W.H.J.; Broxterman, Q.B.; Peters, P.J.H.; Schoemaker, H.E.; Kamphuis, J.
Tetrahedron: Asymmetry 1993, 4, 1113.

Note: this Tetrahedron article would be interesting to read.......java

Just hold on to the thread...that keeps us going
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java
(Hive Addict)
08-18-04 20:10
No 526168




Summary of Phenylalanine to Amphetamine
Bookmark Reply

Phenylalanine is either refluxed with formic acid under a dean-stark trap or mildly reacted with acetyl-chloride or acetic-anhydride to form the formyl or acetyl amide, respectively. Then phenylalanine or any of the amides mentioned above are reduced with sodium borohydride and iodine in THF to form the aminoalcohol or its N-alkylated version. Yes, you read right! In an analogue to the reduction of phenylalanine using sodium borohydride/sulfuric acid formerly posted -- I think -- at the beginning of this thread, amides of phenylalanine are successfully reduced into their respective N-alkylated aminoalcohols in about 85-95%, if I remember correctly.

........as read in Post 108597 (dormouse: "drone's amphetamine synthesis contest -drone 342", Novel Discourse) the comment by Psychokitty

Hence a summery of where we are. Now we are able to either reduce Phenylalanine with the NaBH4+I , and get Phenylalaninol or we can first methylate the amine by the above method and react it with NaBh4 + I in THF and get N-Methyl-Phenyalaninol. Employing the method and reference provided by Psychokitty NaBH4Al(II) will reduce this amino acid to it's respective hydrocarbon. the alternative is the method that was proved by .....

Labrat
Member   posted 12-24-98 09:38 AM
--------------------------------------------------------------------------------
.......This aminoalcohol is reduced by HI/red P at reflux to amphetamine. The validity of this method has recently been proven by Assholium (thanks!). Lr/

found in the same post Post 108597 (dormouse: "drone's amphetamine synthesis contest -drone 342", Novel Discourse)

So now we have a method to either amphetamine or methedrine depending which route you take. However the essential catalyst and solvents remains being NaBH4, I2, THF, acetic anhydride.

I will find the thread were Assholium talks about this method of reducing with the well known RP/I but with some modifications from what I herd, 11/2 the amount of I as normally used in the reduction of ephedrine /Pseudoephedine.........java

References offered by Psychokitty in the comments quoted, the synthesis article is posted on this thread the others would be nice to secure to include with this thread....

JOC 1993,58,3568-3571 "A Convenient Reduction of Amino Acids and Their Derivitives".

And for the subsequent reduction of the primary alcohol I offer some super-duper stratagies and their references:

JOC 1992, 57, 2143-2147 "Reductive Deoxygenation of Ketones and Secondary Alcohols by Organoaluminum Lewis Acids".

SYNTHETIC COMMUNICATIONS, 26(24),4647-4654(1996) "Deoxygenation of Acylferrocenes with Sodium Borohydride and Zinc Chloride".

And the very fucking best of the lot:

Synthesis 1987, pp.736-738 "Hydrogenolysis of Diaryl and Aryl Alkyl Ketones and Carbinols by Sodium Borohydride and Anhydrous Aluminum (III)Chloride"

It is better to die on your feet than to live on your knees.......
-Emiliano Zapata-

java
(Hive Addict)
08-19-04 13:47
No 526326




Phenylalanine to amphetamine continuation.....
Bookmark Reply

I have a question which I need some help answering , in the hydrogenolysis of OH to CH3 of Phenylalaninol as mentioned in my last post where Assholium proved that RP/I would reduce the alcohol to the respective hydrocarbon, keeping in mind that Phenylalaninol is slightly soluble in water.

Now water is needed for the chemistry of RP and I to work into making HI and catalyse it to reduce the OH to CH3. As noted and mentioned by Rhodium Post 521414 (Rhodium: "Note the formation of HCl salts in the reaction", Serious Chemistry) on this thread the solubility of phenylalaninol and most amino alcohols are soluble in chloroform and DMF. But does that mean that the reaction solvent will be chloroform? Doubtful, hence it would be nice to find out the solvent Assholium used in his method which he showed this reduction of the alcohol to hydrocarbon.

So if there is anyone out there that has the answer, since I wrote to Assholium and no response, It would be nice to add to this project.......java

It is better to die on your feet than to live on your knees.......
-Emiliano Zapata-

java
(Hive Addict)
08-19-04 17:02
No 526340




RP/I in the reduction of Phenylalaninol....
Bookmark Reply

I found this info as to using RP/I .....

Yes, it is possible to reduce most alcohols to the corresponding hydrocarbons with Hydriodic acid (for example made in situ by RP/I2). But as Phenylalaninol is a standard aliphatic alcohol rather than a benzylic alcohol (as in the case of (pseudo)ephedrine) the reduction is harder to perform, and you may need a larger excess of Hydriodic acid or a longer reflux time to pull it off. If you are going to try to reduce Phenylalaninol, I suggest that you start out with at least a 24h reflux and 1.5 times as much HI (or RP/I2) as you usually use to reduce (pseudo)ephedrine.

........as posted in Post 459611 (Rhodium: "Reduction of Phenylalanine to Phenylalaninol", Stimulants)

Note: I sometimes feel like I'm talking to myself.....

Edit: here are some articles that deal with RP/I ....

I would like to read this two

Reagents for Organic Synthesis, Vol. 1,
Wiley, 1967, p. 449.
L. Fieser and M. Fieser

Survey of Organic Synthesis, Wiley andSons, 1970, p. 7 and p. 332.
C. Buehler and D. Pearson

this last one is available ....

methedrine Synthesis Via HI/Red Phosphorous Reduction of Ephedrine
Harry F. Skinner
Forensic Science International, 48 128-134 (1990)

aound here....Post 58319 (SuperAssman: "Interesting info from legit sci-dude", Stimulants)

It is better to die on your feet than to live on your knees.......
-Emiliano Zapata-

Organikum
(Wonderful Personality)
08-20-04 08:43
No 526466




Deoxygenation of benzhydrols
Bookmark Reply

There are more methods available some of which have not been talked about by now:

I except those which for sure only work on alpha-alcohols like the Li/ammonia (Birch)and those already mentioned.

Here we go:
1. Fe(CO)5
2. Diiododimethylsilane
3. Zinc iodide/sodium cyanoborohydride
4. Triphenylsilane in trifluoroacetic acid/methylene chloride
5. Sodium borohydride/trifluoroacetic acid

1. Alper, H.; Salisova, M. J. Org. Chem. 1980, 21, 801.
(this one would 9interest me in special as I have never heard of Fe(CO)5 as reducing reagent before - very curious I am!
2. Ando W.; Ikeno M. Tetrahedron Lett. 1979, 1979.
3. Lau C. K.; Dufresne C.; Belanger C. P.; Pietre S.; Scheigetz J. J. Org. Chem. 1986, 51, 3038.
4. Olah G. H.; Tremper H. S. J. Am. Chem. Soc. 1968, 90, 2578.
5. Gribble G. W.; Leese W. M.; Evans B. E. Synthesis 1977, 763.

And onto the RP/I a remark: Acetic or phosphoric acid are the solvents of choice here. The low solubility of the substrate is not really important - the reaction is heterogenous anyways and the solid substrate being where the HI is formed - at the bottom where the RP is - might even be favorable.

btw. I am rather sure that a suitable noble metal catalyst reduces ANY alcohol when trifluoroacetic acid is used as solvent and perchloric acid as moderator.
Also there was a post times ago by "chicken" AFAIK, where it was told that triethylsilane/aluminiumchloride in trifluoroacetic acid reduces aminoalcohols in yields up to 100%. No reference was given, the post has vanished like so many useful posts did.
Looking at the reagents used in the above references it seems very probable that this works. Silanes have become a mass-product in the last years, not too expensive and not watched by now. They are produced in tons over tons by Wacker-Chemie Burghausen in Germany. (thats no source, you cant buy it from them directly, but your industrial chem-supplier can do so)

ORG

so near, so far......

java
(Hive Addict)
08-20-04 13:47
No 526494




Other methods.....
(Rated as: excellent)
Bookmark Reply

Organikum...check the reference Alper, H.; Salisova, M. J. Org. Chem. 1980, 21, 801.
it doesn't seem to be the right date or page , anyway check so I can find it.

Here is one that I found....

Reactions of Sodium Borohydride in Acidic Media; VII. Reduction of Diaryl Ketones in Trifluoroacetic Acid

GRIBBLE, Gordon W.; KELLY, William J.; EMERY, Sanford E.:

Will look for ...........

Carbonium ion-silane hydride transfer reactions. I. Scope and stereochemistry
Francis A. Carey and Henry S. Tremper
J. Am. Chem. Soc. 1968, 90, 2578.

Reductive deoxygenation of aryl aldehydes and ketones and benzylic, allylic, and tertiary alcohols by zinc iodide-sodium cyanoborohydride
C. K. Lau, Claude Dufresne, Patrice C. Belanger, Sylvie Pietre, and John Scheigetz
Org. Chem. 1986, 51, 3038.

Copper-complexes of pyridazine N-oxides; The synthesis and x-ray studies
Akio Ohsawa, , Toshio Akimoto, Akio Tsuji and Hiroshi Igeta
Tetrahedron Letters Volume 19, Issue 23, (1978)Pages 1979-1982

It is better to die on your feet than to live on your knees.......
-Emiliano Zapata-

Organikum
(Wonderful Personality)
08-20-04 18:07
No 526529




Uhh ?
Bookmark Reply

Alper, H.; Salisova, M. J. Org. Chem. 1980, 21, 801.

This is exactly how its referenced in the article from which I quoted this, with italics and bold......

Cant help it, sorry. Any chance to get hold of it by the authors or the reagent, Fe(CO)5 ?

Damn.

so near, so far......

gsus
(Hive Bee)
08-20-04 20:57
No 526537




Alper and Salisova
Bookmark Reply

right year/volume/page, wrong journal, i think. try Tet Lett.

http://www.mindstates.org/mindstatesoaxaca.html

java
(Hive Addict)
08-20-04 22:44
No 526546




The correct Reference on FE(CO)5
Bookmark Reply

The iron carbonyl induced deoxygenation of alcohols

Howard Alper* and Marta Saliov·

Tetrahedron Letters volume 21 773-890 1980

Abstract

Alcohols, able to form stable carbanions, are deoxygenated to hydrocarbons by treatment with potassium, iron pentacarbonyl, and then hydrochloric acid. Use of an alkyl halide in place of HCl results in reductive alkylation.

It is better to die on your feet than to live on your knees.......
-Emiliano Zapata-

7is
(Hive Bee)
08-20-04 22:50
No 526547




Articles
(Rated as: excellent)
Bookmark Reply

A convenient reduction of amino acids and their derivatives
Marc J. McKennon, A. I. Meyers, Karlheinz Drauz, and Michael Schwarm
JOC 1993,58,3568-3571

Organometallic compounds of Group III. 49. Reductive deoxygenation of ketones and secondary alcohols by organoaluminum Lewis acids
John J. Eisch, Zhi Rong Liu, and Marek P. Boleslawski
JOC 1992, 57, 2143-2147

Carbonium ion-silane hydride transfer reactions. I. Scope and stereochemistry
Francis A. Carey and Henry S. Tremper
J. Am. Chem. Soc. 1968, 90, 2578.

Copper-complexes of pyridazine N-oxides; The synthesis and x-ray studies
Akio Ohsawa, , Toshio Akimoto, Akio Tsuji and Hiroshi Igeta
Tetrahedron Letters Volume 19, Issue 23, (1978)Pages 1979-1982

The iron carbonyl induced deoxygenation of alcohols
Howard Alper and Marta Salisova
Tetrahedron Letters 1980, 21, 801.

java
(Hive Addict)
08-21-04 16:26
No 526633




Phenylalaninol reduction .......
Bookmark Reply

Organikum...maybe it's this article that you mentioned that dissapeared....

Selectivities in ionic reductions of alcohols and ketones with triethylsilane/trifluoroacetic acid
Herbert Mayr*a) and Barbara Doganb)

Tetrahedron Letters Volume 38, Issue 6 , 10 February 1997, Pages 1013-1016
DOI::10.1016/S0040-4039(96)02484-7

Abstract
The relative rates of reduction of alcohols and ketones by Et3SiH/CF3CO2H have been determined by competition experiments in order to derive scope and selectivities of these reactions.
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As for the articles mentioned in the removal of OH groups I think the Fe(CO)5 has the most viability as the others seem to get busy real fast. Thanks to 7is there is a chance to read all of them and evaluate for one self.

Although the reduction of such secondary alcohols by this procedure proceeded smoothly and in satisfactory overall yields, the attempted reductions of primary alcohols and phenols, such as 1-nonanol and p-cresol, led to no conversion at all.

.....from"JOC 1992, 57, 2143-2147 "Reductive Deoxygenation of Ketones and Secondary Alcohols by Organoaluminum Lewis Acids"., hence althugh it may be good for Ephedrine ,a secondary alcohol, for our case it won't work.

My favorite so far is Hydrogenolysis of Diaryl and Aryl Alkyl Ketones and Carbinols by Sodium Borohydride and Anhydrous Aluminum(III) Chloride Synthesis 1987; 736-738   Post 523004 (java: "Hydrogenolysis of Phenylalaninol.....", Serious Chemistry)which may be a solution for both this primary amino alcohol and the secondary amino alcohol, ephedrine.

SYNTHETIC COMMUNICATIONS, 26(24),4647-4654(1996) "Deoxygenation of Acylferrocenes with Sodium Borohydride and Zinc Chloride". may have some more clues. I will try to find it or maybe someone else could find it.

Noted in the articles retrieved the one mentioned in her reference Psychokitty "A Convenient Reduction of Amino Acids and Their Derivatives" the issue of acylating the amino acid Phenylalanine prior to reduction to the alcohol is covered as to get n-methyl-Phenylalaninol. A very good article that should be a must read if you're following the issues on this thread.....java

It is better to die on your feet than to live on your knees.......
-Emiliano Zapata-

Organikum
(Wonderful Personality)
08-25-04 13:03
No 527294




not found
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Tetrahedron Letters Volume 38, Issue 6 , 10 February 1997, Pages 1013-1016
DOI::DOI:10.1016/S0040-4039(96)02484-7

DOI not found ?

so near, so far......

java
(Hive Addict)
08-25-04 15:08
No 527307




The missing Tetrahedral article....
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Here it is, it was already uploaded .....but was not found easy with the search ......java

Post 514666 (scarmani: "Et3SiH / TFA Reduction - Improvements?", Serious Chemistry)

edit: I underestand the article is not found on the bord, so heere is the copy.....java

Selectivities in Ionic Reductions of Alcohols and Ketones with
Triethylsilane / Trifluoroacetic Acid
Tetrahedron Letters, Vol. 38, No. 6, pp. 1013-1016, 1997

It is better to die on your feet than to live on your knees.......
-Emiliano Zapata-

java
(Hive Addict)
09-03-04 15:58
No 529405




phenylalaninol reduction RP/I.......
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After searching through the archives here at the Hive and asking questions from knowledgeable bee's I've been able to deduce the following which can be found and read from this thread,

1. Phenylalaninol can be reduced with the RP/I method , only increasing the reactants 1.5 as much as regularly used in the reduction of ( Pseudo) Ephedrine and at least a 24 hr. reflux as recomended by Rhodium

2.The solubility of the alcohol is slight in water, hence recomended acidic acid or Phosphoric acid.

3. There is a concern brought to my attention as to cyclozation producing cycloamines, but I wonder if by running the reaction with 1.5 in excess of the reactants will create a strong acidic environment , as recomended to avoid this.

4. there is out there a post by Assholium where he gave details of the reaction and proof of its viability.....one quoted by Labrat

Note: Trying to complete this reaction with availabe methods already know here at the hive. Yes there is the NaBh4 Al(111), the hydrogenation methods the halogenation & hydrogenation methods , the few introduced by Organikum on this thread and those by Psychokitty

Will be looking for the elusive post to bring to light any possible complications with this procedure....java

It is better to die on your feet than to live on your knees.......
-Emiliano Zapata-

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