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All 60 posts   Subject: Phenylalanine to amphetamine continuation.....   Please login to post   Down

 
    java
(Hive Bee)
07-01-04 01:14
No 516647
      Phenylalanine to amphetamine continuation.....     

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

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    Rhodium
(Chief Bee)
07-01-04 03:18
No 516672
User Picture 
      It is much simpler - hoffmann alkylation:     

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 09:21
No 516709
User Picture 
      ... nothing stops it but strongly acidic ...     

... nothing stops it but strongly acidic conditions smile
 
 
 
 
    java
(Hive Bee)
07-01-04 22:24
No 516800
      dimerization/polymerization...     

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)


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    Organikum
(Wonderful Personality)
07-02-04 07:32
No 516916
      For the reduction of the phenylalaninol to the     

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 23:48
No 517271
User Picture 
      -OH to -CH3 and how to get there.....     

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


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    psyloxy
(Hive Addict)
07-04-04 00:31
No 517282
User Picture 
      Re: It should be possible to reduce the ...     


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 18:08
No 518572
User Picture 
      amines to nitriles w/K2S2O8,cat.NiSO4 84-97%
(Rated as: excellent)
    

I know this is a bit off the general line of thought persued here, but it starts with PHE and ends with amph / meth nonetheless. NaBH4/LiAlH4 or chlorinating agents are not needed here. Everything is really quite OTC.

PHE.gif

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 laugh




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. 

Table1.gif

--psyloxy--
 
 
 
 
    psyloxy
(Hive Addict)
07-11-04 04:17
No 518656
User Picture 
      one step shorter     

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 12:33
No 518687
      Here are two articles mentioned by psyloxy in...
(Rated as: excellent)
    

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 Celite® and diluted with distilled water (500 mL). The light green filtrate was loaded on a column (25 cm Ч 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 Celite®, 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 Ч 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 20:07
No 518724
User Picture 
      Phenylalanine to amphetamine continuation.....     

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

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    psyloxy
(Hive Addict)
07-14-04 03:55
No 519297
User Picture 
      more uploads
(Rated as: good read)
    

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 15:21
No 519386
User Picture 
      Interesting     

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 18:10
No 519411
User Picture 
      the practical articles     

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

4-hydroxy-5(3´-cyanopropyl)-2-pyrrolidone (8):

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/cm², 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 15:41
No 519592
User Picture 
      regarding phenylalaninol....     

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 15:54
No 519595
User Picture 
      Probably not     

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.

“The real drug-problem is that we need more and better drugs.” – J. Ott
 
 
 
 
    Lego
(Hive Bee)
07-15-04 17:18
No 519606
User Picture 
      Stereochemistry     

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: "Synthesis of BDB/MBDB (J/Methyl-J)", 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 18:31
No 519617
User Picture 
      Stereo isomerization question on Phenylaninol.....     

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

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    java
(Hive Bee)
07-24-04 20:14
No 521386
User Picture 
      Solubility of Phenylaninol Inquiry...     

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 22:11
No 521414
User Picture 
      Note the formation of HCl salts in the reaction     

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 18:15
No 522028
User Picture 
      Another route to Phenylalaninol.....
(Rated as: good read)
    

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)
07-31-04 02:24
No 522829
      Old HCA Article     

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 wink



cool

Chemistry is our Covalent Bond
 
 
 
 
    java
(Hive Bee)
07-31-04 22:45
No 522980
User Picture 
      More about Phenylalanine....     

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, methamphetamine 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
http://www.chiapaslink.ukgateway.net/
 
 
 
 
    java
(Hive Bee)
08-01-04 01:32
No 523004
User Picture 
      Hydrogenolysis of Phenylalaninol.....
(Rated as: excellent)
    

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 Methamphetamine 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 methamphetamine. Thank you psychokitty for your research........java

Just hold on to the thread...that keeps us going
http://www.chiapaslink.ukgateway.net/
 
 
 
 
    java
(Hive Bee)
08-01-04 20:18
No 523116
User Picture 
      Syntheses of amino alcohols.....     

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 1b–f and 2b,c, derived from 4’-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.

Just hold on to the thread...that keeps us going
http://www.chiapaslink.ukgateway.net/
 
 
 
 
    josef_k
(Hive Bee)
08-02-04 12:33
No 523222
      Re: for which deals with the reduction, to the     


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 methamphetamine. 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. smile

 
 
 
 
    java
(Hive Bee)
08-02-04 16:46
No 523245
User Picture 
      Hydrogenolysis......     


.....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


Just hold on to the thread...that keeps us going
http://www.chiapaslink.ukgateway.net/
 
 
 
 
    armageddon
(Hive Bee)
08-06-04 01:36
No 523910
User Picture 
      Pd/C and solvents     

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)
08-14-04 00:20
No 525336
User Picture 
      Alpha-methyl-Aminoacids .....     

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
http://www.chiapaslink.ukgateway.net/
 
 
 
 
    java
(Hive Addict)
08-19-04 01:10
No 526168
User Picture 
      Summary of Phenylalanine to Amphetamine     


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 methamphetamine 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 18:47
No 526326
User Picture 
      Phenylalanine to amphetamine continuation.....     

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 22:02
No 526340
User Picture 
      RP/I in the reduction of Phenylalaninol....     

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 ....

Methamphetamine 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 13:43
No 526466
      Deoxygenation of benzhydrols     

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 18:47
No 526494
User Picture 
      Other methods.....
(Rated as: excellent)
    

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 23:07
No 526529
      Uhh ?     

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)
08-21-04 01:57
No 526537
      Alper and Salisova     

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

http://www.mindstates.org/mindstatesoaxaca.html
 
 
 
 
    java
(Hive Addict)
08-21-04 03:44
No 526546
User Picture 
      The correct Reference on FE(CO)5     

The iron carbonyl induced deoxygenation of alcohols

Howard Alper* and Marta Saliová

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)
08-21-04 03:50
No 526547
User Picture 
      Articles
(Rated as: excellent)
    

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 21:26
No 526633
User Picture 
      Phenylalaninol reduction .......     

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.
-------------------------------------------------------------------------------------

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 18:03
No 527294
      not found     


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 20:08
No 527307
User Picture 
      The missing Tetrahedral article....     

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 20:58
No 529405
User Picture 
      phenylalaninol reduction RP/I.......     

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-
 
 
 
 
    java
(Hive Addict)
09-05-04 22:41
No 529757
User Picture 
      Another primary -OH reduction method...     

More recently this was posted by Kinetic and thought this to fit nicely in this thread in dealing with the reduction of Phenylalaninol to a hydrocarbon........

Post 529529 (Kinetic: "More reductions with triethylsilane/boranes", Chemistry Discourse)

It is better to die on your feet than to live on your knees.......
-Emiliano Zapata-
 
 
 
 
    nightshade
09-09-04 17:22
      Reducing Phenylalaniol to what using RP/I...
(Rated as: UTFSE!)
    
 
 
 
    Rhodium
(Chief Bee)
09-23-04 17:35
No 532870
User Picture 
      L-Phenylalanine to d-Amphetamine
(Rated as: good read)
    

Überführung optisch aktiver α-Aminocarbonsäuren in optisch aktive Amine mit gleichem Kohlenstoffskelett
P. Karrer & K. Erhardt
Helv. Chim. Acta 34, 2202-2210 (1951) (https://www.rhodium.ws/pdf/pha2amph.ehrhardt.pdf)

Summary:
This is one of the first published methods for the conversion of L-Phenylalanine to d-Amphetamine. First phenylalanine is condensed with methanol to form phenylalanine methyl ester, which is reduced with LiAlH4 to L-Phenylalaninol. This aminoalcohol is reacted with tosyl chloride in pyridine to give L-Phenylalaninol O,N-ditosylate. The O-tosylester was reduced to the hydrocarbon with LiAlH4 to yield D-Amphetamine N-tosylamide, which finally was cleaved to give D-Amphetamine.

The same scheme was applied to L-Tyrosine, transforming it into 4-Hydroxy-Amphetamine.

The Hive - Clandestine Chemists Without Borders
 
 
 
 
    java
(Hive Addict)
09-26-04 00:49
No 533189
User Picture 
      Question on Tosyls.....on route to Amphetamine....     


This aminoalcohol is reacted with tosyl chloride in pyridine to give L-Phenylalaninol O,N-ditosylate. The O-tosylester was reduced to the hydrocarbon with LiAlH4 to yield D-Amphetamine N-tosylamide, which finally was cleaved to give D-Amphetamine.




Rhodium....I'm wondering , since I can't read german, if the author also gives an option to reduced the O-tosylester through catalytic hydrogenation since the tosyl are easy leaving groups or would you know if that is also an option , say using Pd in (don't know ) solvent.......java


It is better to die on your feet than to live on your knees...Emiliano Zapata
 
 
 
 
    Rhodium
(Chief Bee)
09-26-04 21:43
No 533293
User Picture 
      Catalytic de-tosylation     

They do not offer any such procedure in that publication, but I'm sure that it would work, somehow. Someone just needs to perform a literature search for it.

The Hive - Clandestine Chemists Without Borders
 
 
 
 
    java
(Hive Addict)
09-27-04 20:03
No 533429
User Picture 
      phenylalaninol reduction RP/I.......
(Rated as: good read)
    

In searching for a confirmation in March's text,  on the reduction of Phenylalaninol  to Amphetamine  by using the RP\I method....I was able to find this study, once quoted as a needed reference Post 172334 (Rhodium: "HI/P reduction REFERENCES?", Stimulants) and never made available,  in which an arene aliphatic alcohol is reduced to the hydrocarbon with this system.....java


Synthesis of Desoxybenzoins . Deoxygenation with the Red Phosphorous /Iodine system

Tse-Lok Ho, C.M. Wong

Synthesis 161, 1975



Untitled-1_copy.jpg

It is better to die on your feet than to live on your knees...Emiliano Zapata
 
 
 
 
    java
(Hive Addict)
09-28-04 20:37
No 533626
User Picture 
      Reducing Phenylalaninol.......articles     

Mining the web and following up leads in related articles , I came upon a couple of studies dealing with the reduction of arene aliphatic alcohols, checked the archives and found no listings on the HIve and so I present them here now for discussion.......java

Chlorotrimethylsilane/SodiumIodide/Zinc as a Simple and Convenient Reducing System:One pot Deoxygenation of Alcohols and ethers

Tsuoshi Morita, Yoshiki Okamoto, Hiroshi sakurai
Synthesis 32, 1981



deoxygenation_schematic.jpg

Note: with this method both primary and secondary alcohols are reduced to hydrocarbons




Synthetic Method and Reactions;47. AlCl/Pd-Catalyzed Reduction of Aryl Substituded Alcohols and Olefins by Hydrogen Transfer from Cyclohexene

George A. Olah ; G.K. Surya Prakash

Synthesis 397, 1978



hydrogen_transfer_.jpg

Note: with this method it seems only benzylic alcohols are reduced, might be a good way to reduce Pseudo-ephedrine......


Edited.....by java


It is better to die on your feet than to live on your knees...Emiliano Zapata
 
 
 
 
    nightshade
(Newbee)
09-29-04 17:26
No 533768
      Fermenting phenylalanine in a bio brew like...     

Fermenting phenylalanine in a bio brew like that producing L-Pac will will produce phenylalaniol, which can be extracted with a non polar solvent then reduced by electrochemical reaction to amphetamine is this correct?
 
 
 
 
    java
(Hive Addict)
09-29-04 21:21
No 533796
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      Biotransformation of Phenyalanine.........?     

nightshade....  do you have some references for that?..........I myself not familiar with the way you've outlioned the procedure.....java

It is better to die on your feet than to live on your knees...Emiliano Zapata
 
 
 
 
    indole_amine
09-30-04 00:09
      I guess he meant some enzymatic conversion of...
(Rated as: insignificant)
    
 
 
 
    nightshade
(Newbee)
09-30-04 17:22
No 533923
      Post 9775,Post 10417     

Post 9775,Post 10417
 
 
 
 
    java
(Hive Addict)
09-30-04 17:34
No 533926
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      Biotransformation References....to Phenylalaninol     

I just put brackets around the post number you volunteered as reference and this is what came up, hence it's easier to just click and go to it than having to go to the search engine looking for them. This will help your posting next time you want to reference a post number............java


Post 9775 (in_outsider: "Tryptophol from Tryptophan via yeast", Tryptamine Chemistry)
Post 10417 (psyloxy: "Re: Tryptophol from Tryptophan via yeast", Tryptamine Chemistry)

P.S. Thank you for the reference as I will read it and comment if I have any questions or suggestions

It is better to die on your feet than to live on your knees...Emiliano Zapata
 
 
 
 
    java
(Hive Addict)
10-01-04 00:05
No 533979
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      Missing one of two ref on RP/I reductions     

Thanks to gsus he has provided the referenced article Post 533954 (gsus: "Fieser and Fieser for java", Novel Discourse)....that was posted by Labrat...on the reduction of Phenylalaninol with the RP/I method ......java

Labrat
Member   posted 08-31-98 09:57 AM          
--------------------------------------------------------------------------------
Labrat has already proposed a method to reduce that -OH to an alkane by a known method: HI/red P reduction. This reagent is
used in the literature to reduce carbonyl, nitrite, halide and ALCOHOL groups.
For those who like literature:

"Reagents for Organic Synthesis" vol 1: p.449 ('67)
"Survey of Organic Synthesis" vol 7 .332 ('70)

Thanks Stony for the refs!~ Lr/



......... as read in Post 108462 (dormouse: "Action of (CH3)2SO4 on phenylalanine  -Labrat", Novel Discourse)
                          Post 101706 (Labrat: "DLPA reduction with H2SO4", Chemistry Discourse)

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




Note.....edited by java


It is better to die on your feet than to live on your knees...Emiliano Zapata
 
 
 
 
    java
(Hive Addict)
10-03-04 01:58
No 534221
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      RP/I Reduction of aminoalcohol.......     

Preparation of alpha ,alpha -Dimethyl- and N,alpha ,alpha -Trimethyl-beta -cyclohexylethylamine
Bernard L. Zenitz, Elizabeth B. Macks, Maurice L. Moore
J. Am. Chem. Soc. 70, 955-957 (1948) (https://www.rhodium.ws/pdf/hi-rp.aminoalcohol2amine.pdf)

Excerp......
A reduction of alpha-methyl-norephedrine to alpha-methyl-amphetamine (Phentermine) with HI/P (80-88% yield). They use 20g RP to 0.4 moles of the aminoalcohol (66g, it has the same molar weight as ephedrine) together with 170 mL 57% HI. The mixture is reacted for 25h at reflux and 12h at room temp before workup (filtration, thiosulfate addition, acid/base extraction, distillation, gassing w/ HCl).

pdf is located at ......
Post 511694 (Rhodium: "HI/RP reduction of aminoalcohols", Stimulants)

It is better to die on your feet than to live on your knees...Emiliano Zapata
 
 
 
 
    java
(Hive Addict)
10-21-04 17:21
No 536977
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      RP/I Reduction of aminoalcohol.......     

There seems to be very little information of the reduction of primary non benzylic type alcohols using the RP/I method.  Although several recomendations have been made as to how and what solvents to use as of yet no hands on reporting nor  information on the elusive method used by a fellow hive Assolium

I have mined the Web for articles on the method but to date no success, also I have mined the Hive archives and no reports of anyone doing the reduction via the RP/I method.  However I have since herd of somone who has tried the method and will report the problems that were encountered and the results which I will post as soon as they are available to me.

There is also efforts to reduce the OH group with the Lucas reagent to chlorinate the OH with the recomendation of warming up the solution to be chlorinated for better results.
Post 536042 (WizardX: "halogenation", Stimulants)
Then the resulting chlorinated Phenylalaninol, which I don't know what it will be called....chloro-phenylpropane? will be hydrogenated with Pd and reduced to Amphetamine HCl.

I wonder if anyone can do a Belstein search for primary non benzylic amino alcohol reduction to alkanes   I tried using the search function but it won't let me in even though I registered.........java

It is better to die on your feet than to live on your knees...Emiliano Zapata
 
 
 
 
    java
(Hive Addict)
10-26-04 17:37
No 537932
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      Hydrogenation and Hydrogenolysis of Alcohols     

Note.... thanks to Azole for aquiring the article  Post 537928 (azole: "retrieved...", Novel Discourse)

Hydrogenation and Hydrogenolysis. IV. Catalytic Reductions of Cinnamyl Alcohols and 3-Phenylpropargyl Alcohol
S. Nishimura, T. Onoda and A. Nakamura
Bull. Chem. Soc. Japan, 1960, 33, 1356-1359.



I think with this information it may then be possible to dehydrate our alcohol with reflux in H2SO4 which will give us a alkene type bond either between the C1-C2 which would be the most stable position, or the C2-C3 which I think either position  can be hydrogenated to the alkane with this procedure..... The Phenylalaninol , unprotected, will most likely not be affected by the acidic environment and leave the NH2 untouched........at least I 'm hoping that's the case......java

It is better to die on your feet than to live on your knees...Emiliano Zapata
 
 
 
 
    indole_amine
(Hive Bee)
10-29-04 00:30
No 538394
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      phenylalanine hydrogenation with Ru/C     

You could also hydrogenate with 5% Ru/C to get the phenylalaninol at the very beginning...


Stereoretentive C-H Bond Activation in the Aqueous Phase Catalytic Hydrogenation of Amino Acids to Amino Alcohols
Frank T. Jere, Dennis J. Miller, and James E. Jackson

Org. Lett., 5 (4), 527 -530, 2003



Abstract
At 100 C and 1000 psi of hydrogen, aqueous L-alanine undergoes facile hydrogenation to L-alaninol over a 5% Ru/C catalyst. In the presence of added acid to protonate the carboxylate moiety, the reaction is faster and more selective than analogous reductions of simple alkanoic acids. Stereochemistry at the -carbon is retained despite complete exchange of hydrogen at this site, as shown by deuterium incorporation. Similar stereoretentive C-H bond activation at C2 is seen in L-alaninol itself, and when acid is omitted, in L-alanine. These processes reveal a class of mild, highly stereoretentive C-H bond activations occurring in water over a heterogeneous catalyst.



indole_amine
 
 
 
 
    java
(Hive Addict)
10-31-04 17:58
No 538932
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      Amino acids to Nitriles minus one Carbon     

NoteThe full article can be found at Post 538899 (Lego: "TCICA: Decarboxylation of amino acids to nitriles", Novel Discourse)  I made note of this article here as, as I understand it , it can be used with n-methylated phenylalanine followed by a conversion from a nitrile to the desired amine

Conversion of alpha-Amino Acids into Nitriles by Oxidative Decarboxylation with Trichloroisocyanuric Acid
Gene A. Hiegel, Justin C. Lewis, and Jason W. Bae
Synth. Comm., 2004, 34(19), 3449-3453
DOI::10.1081/SCC-200030958


Abstract: Trichloroisocyanuric acid oxidation of alpha-amino acids in water or methanol in the presence of pyridine produces nitriles with one less carbon in good yields and of high purity.

Keywords: alpha-Amino acids; Nitriles; Oxidative decarboxylation; Oxidation; Decarboxylation; Preparation; Synthesis; Trichloroisocyanuric acid


Note: I hope this is not considered cross posting as i only wanted to make this method available to the concept of this thread....java

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

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