java (Stranger)
04-29-02 00:31
No 302723
      Tentatively meth.......     

I tried this post but I was wrong in my conclusion and admited it and so I try again.  I don;t know how to paste into this formula diagrams and hence will talk it through.

I Propose that,

If you start with the amino acid Phenylalanine and then do the Dakin-West reaction , one which add and anhydride, in the presence of pyridine,  the carboxyl group is prplaced with a acytl group and the NH2 becomes acylated.  Now you have an oxazolone.

This is essentially  a double ester  one on the number three carbon  and the other off the NH side branch on the alpha carbon.   Now by doing an ester reduction one ends with a OH  off the main chain and the side chain , so by reduction of an alcohol  to an alkene with H2So4, then we finish it off by catalytic hydrogenation to make it an meth-amphetamine needing HCL to make it a salt,,,,,,,,,,,,,,,I think?cool  any comments, I've looked at this and it seems sound........
 
 
 
 
    java
(Stranger)
05-07-02 21:33
No 305874
      re-tentative meth, addendum     

And now for some illustrations of the claim route to meth.
Phe-Ch2-CH(-NH2)-COOH >>>>>>Phe-CH2-CH(-NHCOOCH3)-COOCH3
Dakin-West Reaction

H.D.Dakin, R.West, J. Biol.Chem.78,91,745,757(1928)
Attenburrow et al, J.Chem.Soc.,1948,310
Cleland,Niemann,J.Am.Chem.Soc.71,841(1949)
Huisgen et al,Agnew. Chem.(Internatl. Ed.) 3, 136(1964); Knorr, ibid,4,705(1965)
Singh, Singh, Tetrahedron Letters 1964(50),3789


Note : Resource for illustrated reactions at:

  [url=http://http://www.liv.ac.uk/Chemistry/Links/reactions.html
Ester  reaction(typical)
R-C=O-OR'>>>>>>Hydrogenation (to an aldehyde then to a primary alcohol
>>>>>RCH2oOH......

I only assume that both ester functional groups go through the same reaction both at the alpha carbon and the carboxyl atom.

If so then the removal of the hydroxy on both the number 3 carbon and the alpha chain by halogenation or by the use of H2SO4 to make an alkene and then hydrogenation with palladium, or maybe phosphorous tri chloride would make the hydroxyl a better leaving group for the replacement with hydrogen through hydrogenation. At the end  chlorination is needed to make the meth salt crystals.

Here is where catalytic hydrogenation really pays off......

It would be nice to get some comments , either I'm flying without any wings or just need some pointers, either way your feed back is welcomed
smile
 
 
 
 
    java
(Stranger)
05-09-02 08:08
No 306616
      re- tentative meth addendum     

Note :March's 5th edition page 1552 section19-39
"reduction of carboxylic acids and esters to alkanes.

                      trichlorosilane procedure
RCOOR'>>>>>>>>>>>>>>>>>>>>>>>>RCH3 +R'OH
and ArCOOH>>>>>>ArCH3

So, then to our phenylalanine once converted by the Dakin-west reaction  to an ester this procedure would give us our finish product save the HCl....... I think?
 
 
 
 
    java
(Hive Bee)
12-02-02 18:43
No 385536
      Re:phenylalanine to meth     



Here is some info on Trichlorosilane , its use will convert  esters into alkanes, in our case the double esters giving us our alkanes in the desired positions.

I have had no feed back on this post , I feel its a viable method  and will run a trial see if in fact things happen as they should only need I use pyridine as my solvent in the Dakin -West reaction or can one use something different as I can't get that out here.

Saludos,(Greetings) from Latin America



Trichlorosilane
Trichlorosilane, HSiCl3, is a colorless, toxic, flammable, corrosive liquid having a vapor pressure of 9.67 psia (6.7 kPa) at 70F (21C). It is shipped under nitrogen pressure of 20 psig (138 kPa).

Applications
Epitaxial deposition of silicon, especially for thicker (>5 microns) layers where an abrupt transition profile and tight process control for film thickness are not critical.

Materials Compatibility
Metals: Brass; Stainless Steel; Carbon Steel; Monel

Plastics: Kel-F; PTFE, FEP, and PFA Fluoropolymers resins; PVDF

Elastomers: Viton

Molecular Weight
135.5

Specific Gravity (Air=1)
4.7

MSDS Reference
P-4823e

Odor
Pungent, Suffocating

CAS Registry No.
10025-78-2

 
 
 
 
    java
(Hive Bee)
12-02-02 23:57
No 385634
      Re: Dakin-West reaction     

Here are some facts regarding Dakin-West reaction and how it can be applied to our Phenylalanine. "When an amino acid is treated with an anhydride in the presence of pyridine, the carboxyl group is replaced by an acyl grpup and the NH2 becomes acylated. This is called the Dakin-West reaction. The mechanism involves formationof an oxazolone. The reaction sometimes takes place on carboxyl acids even when an amino group is not present . A number of N-substituded amino acids , RCH(NHR' )COOH, give the corresponding N_alkylated products. " as stated on page 812 from 5th edition March's text.

Ref.
( included in text, but will list for those without access to the March text)
 for a review, see Buchanan, G.L.Chem.Soc.Rev.,1988,17,91 Allinger, N.L.; Wang, G.L. ; Dewhyrst, B.B., Org. Chem., 1974,39,1730

Note : see also Post 194986 (Rhodium: "First published direct reduction of COOH to CH3", Serious Chemistry) where triethylsilane is used where it appears to be a straight shot weather to amphetamine or after the dakin-West to methamphetamine.
 
 
 
 
    Rhodium
(Chief Bee)
04-27-04 22:33
No 503369
      Review: The Dakin-West Reaction
(Rated as: good read)
    

Review: The Dakin-West Reaction
Buchanan, G.L.
Chem. Soc. Rev. 17, 91-109 (1988) (../rhodium/pdf /dakin-west.review.pdf)

This is the reaction mechanism of the classic P2P synthesis which involves reflux of a mixture of phenylacetic acid, acetic anhydride and a weak base (often sodium acetate or pyridine).

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    java
(Hive Bee)
05-07-04 04:32
No 505487
      Dakin West Reaction     

Rhodium thanks for the reference,.... I still feel strong about using this simple method to generate the ketone starting with phenylalanine then reducing it to the alcohol, and the amide group to a methylamine all in one step with hydrogenation with Pd or Pt. The last step to an alkane can be done with the same procedure of hydrogenation using some perchloric acid to initiate the reaction under a acetic acid solvent once the OH has been halogenated with Zn Hcl or PBr3 P/I and on the latter with enough P and I it can be reduced all the way to Ch3. I'm not sure about the reduction of the amide to a methyl amine , an issue long argued , but can be done with hydrogenation in methanol with Pd.

Note: References to the reduction of ketones to alcohols as per Morrison and Boyd 2ed. pg.630 and the reduction of alcohols to alkanes via halogenation of OH,as per Morrison and Boyd 2ed. page 464(Preparation of Alkyl Halides), then catalytic reduction using Pd. as per Rylander text on Hydrogenation with catalysts.

Additional info on the Dakin West Reaction:

http://www.dmapcatalyst.com/Reaction%20Pages/dakin.htm

............... java

We're  all in this world together,
http://www.aztlan.net
 
 
 
 
    java
(Hive Bee)
06-10-04 03:11
No 512515
      Dakin -West Reaction     

This reaction starting with Phenylalanine has been a thorn at my side, but regardless I will still try to make some sense of it.

The reaction produces alpha-acetamido ketone and a ketone which I think they can both be reduced the ketone to an aldehyde then to an OH , halogen then CH3 , while the amide serving as a protection can now be reduced to a methylated amine.

I think I will be able to do some short cuts but I will find the end somehow. It's a challenge and I think I can still yield a >50%  end product weather the amph or the prefered meth......java

Just hold on to the thread...that keeps us going
http://www.chiapaslink.ukgateway.net/
 
 
 
 
    Rhodium
(Chief Bee)
06-16-04 00:48
No 513650
      More on the Dakin-West reaction
(Rated as: good read)
    

The Conversion of Arylacetic Acids into Ketones
G. L. Buchanan and J. McArdle
J. Chem. Soc. 2944-2945 (1952) (../rhodium/chemistry /dakin-west.mechanism.html)

The reaction between phenylacetic acid and acetic anhydride in the presence of pyridine was originally described by Dakin and West (J. Biol. Chem. 78, 91 (1928) (http://www.jbc.org/cgi/reprint/78/1/91)) who noted that the main product was benzyl methyl ketone. King and McMillan (J. Amer. Chem. Soc. 73, 4911 (1951) (../rhodium/pdf /decarboxylative.arylacetic.acylation.pdf)) have re-investigated this reaction and shown that dibenzyl ketone is also formed. They consider the reaction to be a "base-catalysed condensation reaction of two acid anhydride molecules", and propose the above mechanism.



We were also engaged on this same problem, and our results are very similar. We agree that the reaction is essentially that of an acid anhydride in the presence of a base, but disagree with the mechanism proposed for these reasons. If the reaction is a condensation reaction as shown above, the essential step is the acylation of the reactive methylene group by a molecule of anhydride. It would therefore be expected that the similarly active methylene group of phenylacetic ester would be acylated under the reaction conditions, yielding ethyl α-phenylacetoacetate. This, we find does not take place. Even the more reactive benzyl cyanide, which would be expected to yield α-acetylbenzyl cyanide, fails to react, and in each case the starting material was recovered in almost quantitative yield. Moreover, such a mechanism assumes that a β-keto-acid anhydride will readily lose carbon dioxide, although it is known that at least one such substance (I) (Schinz and Hinder, Helv. Chim. Acta, 1947, 30, 1372) is relatively stable.



We envisage a migration mechanism as the only one which satisfactorily accounts for all the facts:



The rearrangement step finds a parallel in the O → C migration of the acyl group in acylated β-keto-esters (Claisen, Ber., 1900, 33, 3778). It is also possible that the recently reported rearrangement of the enol acetates of ketones (Hauser et al., J. Amer. Chem. Soc., 1950, 72, 3635) represents a less favourably activated example of the same reaction.

Experimental

Ethyl phenylacetate (45 g) was refluxed for 20 hours with acetic anhydride (125 mL) and dry pyridine (125 mL). The anhydride and pyridine were then removed in vacuo and the residual liquid fractionated. The product (43 g), bp 115C/15 mm., gave an amide, mp 157C not depressed on admixture of the specimen with an authentic sample of phenylacetamide.

Benzyl cyanide (30 g.) was refluxed for 9 hours with acetic anhydride (100 mL.) and dry pyridine (100 mL.), and then worked up as before. The product (27 g.), bp 108C/15 mm., gave a benzylidene derivative, mp 86C, not depressed on admixture of the specimen with α-cyanostilbene.

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