Author Topic: P2P - 100% OTC !?!  (Read 6204 times)

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  • Guest
Re: P2P - 100% OTC !?!
« Reply #20 on: October 19, 2001, 10:43:00 PM »
joyman, could you pm the article to aurelius, couldn't actually get the ref from aurelius' source.  that comment on the base might have been off a bit, that was from memory.  it's a condensation rxn, then decarboxylation by heating or something like that.  but please send that article to aurelius.


  • Guest
Re: P2P - 100% OTC !?!
« Reply #21 on: October 20, 2001, 04:29:00 AM »
Ratio, 2 moles of benzaldehyde to 1 mole of alanine. Wasteful!
I would rather use the benzaldehyde + nitroethane.
The alanine is reduced via -COOH => -CH2-OH = I2/RP=> -CH3


  • Guest
Re: P2P - 100% OTC !?!
« Reply #22 on: October 20, 2001, 09:32:00 AM »
I agree that the double stage reaction is not elegant considering that its synthing up something quite close to meth (ppa) only to decompose it back to p2p. But from what I can tell it *is* cheap, otc and bloody simple. (and no pills!). React with methylamine -> meth

Using rp/i and ppa to yield the inferior non n-methylated amphet doesnt seem worthwhile (and defeats the purpose since both i and rp are hard to obtain) . I cant find a good otc route to nitroethane otherwise this is the standard to p2p from bzcho.

Aurelius, Hows your German? Like I said I coulnt get the japanese article (Journal != Bulletin). Ive got a German one talking about something similar photocopied in storage but I can image-scan. From what i could make out it was done in a solvent, controlled temp, wait until c02 stops evolving off. They did it with just about every common amino acid.

Synthesis of aminoalcohols by aldol condesation of aminoacids with aromatic aldehydes.


  • Guest
Re: P2P - 100% OTC !?!
« Reply #23 on: October 22, 2001, 09:31:00 PM »
If someone can get the details out of these article it would bee really nice!

Stereospecific synthesis of ?-amino-?-hydroxy acids
J. Org. Chem. 44, 3967-9 (1979)

Reaction between aromatic aldehydes and ?-amino acids. I. New facts on the Akabori reaction.    
Takagi, Eiichi.
J. Pharm. Soc. Japan  (1951),  71  648-51.  

The Akabori reaction (I) (C.A. 41, 3774g) on BzH and dl-MeCH(NHMe)CO2H (II) with and without pyridine and removal of the unreacted BzH by steam distn. gave dl-ephedrine and dl-y-ephedrine.  Similarly, direct heating of piperonal and II gave 2 dl-1-(3,4-methylenedioxyphenyl)-2-methylamino-1-propanols. A new reaction (III), differing from I, takes place on heating BzH and DL-alanine directly; PhCH2NH2, PhCH(OH)CHPhNH2 (2 dl-compds.), AcH, and CO2 are formed.  It is considered that the I-type reaction occurs when the N of the amino acid is secondary and the III-type reaction when it is primary. 

Chemical reactions of amino acids with aldehydes. I.
Synthesis of chloramphenicol by the Akabori reaction.    

Emoto, Sakae; Ando, Makoto.  
Nippon Nogei Kagaku Kaishi  (1961),  35  663-7.

O-Methylserine (10 g.) and 45-50 g. p-nitrobenzaldehyde refluxed in 500 ml. C5H5N gave 14.2-17.4% dl-threo-1-p-nitrophenyl-2-amino-3-methoxy-1-propanol (dl-I), m. 136-7° [I. HCl m. 205-7° (decompn.)], 23.2% ?,?-bis(p-nitrophenyl)ethanolamine (II), m. 183° (decompn.), 0.9% p-nitrobenzylamine (III) [HCl salt m. 265° (decompn.)], and a trace of b-methoxyethylamine (IV). dl-I refluxed with concd. HBr soln. gave dl-threo-1-p-nitrophenyl-2-amino-1,3-propanediol, m. 140-1°; HCl salt m. 180-1°; deriv. m. 169°. dl-I (1.5 g.) and 15 g. Cl2CHCO2Me heated 2 hrs. gave 72% dl-threo-1-p-nitrophenyl-2-dichloroacetamido-3-methoxy-1-propanol (V), m. 104°.  V (1 g.), 4 g. anhyd. ZnCl2, and 10 g. AcCl refluxed 2 hrs. gave 62% dl-chloramphenicol, m. 149-50°.  dl-I was resolved by treatment with d-tartaric acid; d-I d-tartrate m. 189-90°, and d-I m. 145°.  Chloramphenicol, m. 150°, was obtained from d-I. 

Chemical reactions of amino acids with aldehydes. VI.
Decarboxylation of an N-methylamino acid by an aromatic aldehyde

Emoto, Sakae; Ando, Makoto.
Nippon Nogei Kagaku Kaishi  (1961),  35  1027-9. 
N,O-Dimethylserine was refluxed 25 min. with benzaldehyde in pyridine to yield 48% 1-phenyl-2-methylamino-3-methoxy-1-propanol, m. 71°; HCl salt m. 175°; picrate m. 165°.  The reaction of p-nitrobenzaldehyde with N,O-dimethylserine under the same conditions gave 2 isomers of N-methyl-?,?-bis(p-nitrophenyl)ethanolamine [m. 198° (decompn.), yield 18.8%, and m. 157-8°, yield 14.3%] and 1-p-nitrophenyl-2-methylamino-3-methoxy-1-propanol (picrate m. 188°, yield 9.1%).  Thus, whereas benzaldehyde did not give N-methyl-?,?-diphenylethanotamine, p-nitrobenzaldehyde gave N-methyl-?,?-bis(p-nitrophenyl)ethanolamine.  Based on the above observations, the formation of a mesomeric anion was proposed as a possible intermediate. 

In the following article they produce the following, which could be decarboxylated to something useful. 

1,3-Benzodioxole-5-propanoic acid, ?-amino-?-ethyl-?-hydroxy-, methyl ester, hydrochloride
Phenylalanine, ?-hydroxy-?-methyl-, methyl ester, hydrochloride

Synthesis of amino acids and related compounds.  3. 
Stereoselective syntheses of ?-alkyl-?-hydroxy amino acids.

Chem. Ind. (London)  (1973),  No. 5  228-9. 

Reaction of CNCHRCO2Me (I; R = Me, Et, CHMe2) with arom. aldehydes (II: R1 = R2 = R3 = H, OMe; R1R2 = OCH2O, R3 = H) in the presence of base gave intermediate oxazolines which were hydrolyzed to Me esters of ?-alkyl-?-hydroxy amino acids (III).  Reaction of I with the corresponding acid chlorides (IV) gave aroyl amino acid derivs. (V) which were hydrogenated to III.  The ratios of erythro:threo isomers of III were detd. by NMR.


  • Guest
Re: P2P - 100% OTC !?!
« Reply #24 on: October 23, 2001, 06:14:00 PM »
I found

on Rhod's page, but there must be a more OTC/kitchen friendly way to go from (substituted)benzaldehyde to (substituted)propenylbenzene.  Then you're plugged into the performic/peracetic/oxone route to ketone with no EtNO2.



"And if we don't get some cool rules ourselves, pronto, then we'll just be bogus too!"


  • Guest
Re: P2P - 100% OTC !?!
« Reply #25 on: October 26, 2001, 03:07:00 PM »
Try reacting the benzaldehyde with ethyl-Mg-I (grignard), followed by dehydration of the intermediate secondary alcohol (heating with catalytic amounts of KHSO4). Et voilà, propenylbenzene. UTFSE. This has been discussed before, and can also be found in pihkal (BDB/MDBDB/J/methyl-J procedures or whatever).


  • Guest
Re: P2P - 100% OTC !?!
« Reply #26 on: October 26, 2001, 08:27:00 PM »
Hmm... interesting.  The link to Procedure for the Production of Phenylacetone (P2P). Patent # :  DE3200232
(addition for patent application P 30 26 698.9-42) reacts ephedrine with H2SO4 and AlCl3. 

Does PPA just substitute right in?  What's the relationship between PPA -- Ephedrine??


"And if we don't get some cool rules ourselves, pronto, then we'll just be bogus too!"


  • Guest
Re: P2P - 100% OTC !?!
« Reply #27 on: October 29, 2001, 01:40:00 AM »
Ohhh Zool, may I offer my best advice? Do whatever you have to do to get nitroE. You won't need Et2O. V.easy ala knovagel (sp). See a post on R's by ~ Gordon J Alles (sp) 1940ish. The first geezer (apparently) to synth phenylisopropylamine.
Lothe to contradict WizX whom we all respect… dunno what he has against Fe/HCl, which works a treat. Trust me, much better than acetic acid/Hcl. IMHE. Sorry R.

SWILL :-[  is dreamin' a one-pot-shot from aldehyde/nitroE> ketone v.soon. Will post in good faith.

Linoleum: the 13th element!  Now available at all good DIY stores… & Walmart.


  • Guest
Re: P2P - 100% OTC !?!
« Reply #28 on: November 20, 2001, 03:17:00 AM »
See Post 229056 (not existing) .  How about PPA --> N-methyl derivative using this method?

Post 178931 (missing)

(PolytheneSam: "PPA --> meth this easy?", Chemistry Discourse)
Maybe there are other ways to hydrogenate the intermediate.


  • Guest
Chromium(II)Chloride Reduction of Nitroalkenes
« Reply #29 on: December 06, 2001, 07:09:00 PM »
Tetrahedron Letters,Vol.26,No.32,pp 3777-3778,(1985)

Although transformations of nitroparaffins or their salts to carbonyl compounds (the Nef reaction)(14) have been investigated extensively,(15) the readily accessible conjugated nitroalkenes have received little attention. (16-18) The present study may stimulate the use of low-valent transition metal species in the reduction of conjugated nitroalkenes analogous to their applications in the reduction of the corresponding nitroalkanes. (15c, l5d)

The following procedure is representative : chromium(II) chloride(20 mmol, 2.46 g)was placed in a nitrogen-flushed flask equipped with septum inlet and magnetic stirring bar.
Aqueous hydrochloric acid (3%, 30 mL) was injected into the flask followed by the slow addition of the b-nitrostyrene derivative (2 mmol, in 20 mL THF) at room temperature. A moderately exothermic reaction ensued. The mixture was refluxed for 4 hrs. and, after cooling, saturated with sodium chloride. The product was extracted into ether (3 x 30 mL) and worked up in the usual manner.
The crude carbonyl compound was purified using a silica gel column (ether/petroleum ether). The results are summarized in Table I.


Nitroalkene(a)                             Product(b)              Yield=[%]    Ref

2-nitrostyrene                           Phenylacetaldehyde          80        15d
phenyl-2-nitropropene              phenyl-2-propanone         81           4
p-bromo,P2NP                        p-bromo,P2P                   79           4
3,4-diethoxy,P2NP                  3,4-diethoxy,P2P              78           4
1-naphthalene-2-nitropropene   1-N-2-NP                       72           4

(a)Prepared by the published procedure.(2)
(b)All products exhibited physical and spectral characteristics in accordance with the assigned structures. (c)Isolated and unoptimized yields.


1. R. S. Varma and G. W. Kabalka, Synth. Commun., 14, 1093 (1984); Idem, Ibid, 15, 151 (1985).
2. M. S. Mourad, R. S. Varma and G. W. Kabalka, J. Org. Chem., 50, 133 (1985).
3. M. S. Mourad, R. S. Varma and G. W. Kabalka, Synth. Commun., 14, 1099 (1984).
4. M. S. Mourad, R. S. Varma and G. W. Kabalka, Synthesis, 000 (1985).
5. R. S. Varma and G. W. Kabalka, Heterocycles, 23, 139 (1985).
6. R. S. Varma and G. W. Kabalka, Chem. Lett., 243 (1985).
7. R. S. Varma and G. W. Kabalka, Synth. Commun., 15, 000 (1985).
8. J. R. Hanson and E. Premuzic, Tetrahedron, 23, 4105 (1967).
9. T. S. Rao, H. H. Mathur and G. K. Trivedi, Tetrahedron Lett., 25, 5561 (1984).
10. A. Hassner and C. Heathcock, J. Org. Chem., 2, 1350 (1964).
11. S. Ranganathan and B. B. Singh, J. Chem. Soc. Chem. Commun., 218 (1970).
12. The reduction of l-nitrocyclohexene may have produced a significant quantity (-40%) of the corresponding 2-hydroxycyclohexanone.
13. It has been reported that chromous acetate generates carbonyl compounds from oximes which have been acetylated. {See E. J. Corey and J. E. Richman, J. Am. Chem. Soc., 92, 5276 (197O)}.
14. J. U. Nef, Justus Liebigs Ann. Chem., 280, 264 (1894).
15. For leading references see
(a) N. Kornblum, A. S. Erickson, W. J. Kelly and B. Henggeler, J. Org. Chem., 42, 4534 (1982);
(b) D. Seebach, E. W. Colvin, F. Lehr and T. Weller, Chimia, 33, 1 (1979)
(c) T.-L. Ho, Synthesis, 1 (1979);
(d) J. E. M&furry, Acc. Chem. Res., 7, 281 (1974); W. E. Noland, Chem. Rev., 55, 137 (1955) and references cited therein.
16. R. T. Gilsdorf and F. F. Nord, J. Am. Chem. Soc., 74, 1837 (1952).
17. A. B. B. Ferreira and K. Salisbury, J. Chem. Soc., Perkin Trans. II, 995 (1978).
l8. H. B. Hass, A. G. Susie and R. L. Heider, J. Org. Chem., 15, 8 (1950).

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