PPA from benzaldehyde & nitromethane

[IOC]

I have UTFSE and get very confusing answers, if anyone could straighten this out would be appreciated.
Is it suggesting nitromethane could also be used to make
Phenylpropanolamine (2-amino-1-phenyl-1-propanol)    (norpseudoephedrine) ??

As per post No 226609
(c) Method of Kamlet (3).  Benzaldehyde (106 g., 1 mole) was vigorously agitated with sodium bisulfite (110 g., 1.06 mole) in 500 ml of water until the formation of the addition compound was complete.  Simultaneously, nitroethane (or nitromethane) (82.5 g., 1.10 mole) was dissolved in a solution made from sodium hydroxide (45 g., 1.125 moles) dissolved in 200 ml of water.  This solution was gradually added, with agitation and at room temperature, to the addition product of benzaldehyde and sodium bisulfite.  After stirring for a half hour, the mixture was allowed to stand overnight.  The lower layer was discarded and the upper layer was dissolved in ether and washed with sodium bisulfite solution.  The ethereal solution was dried over Drierite, and after removal of ether, distilled (bp 120-130 @ 2-4 mm).  The usual conversion is 90-100g. (50-55%) and the yield, based on benzaldehyde which reacts is nearly quantitative.

Preparation of 2-amino-phenyl-1-propanol.  (a) With zinc and sulfuric acid.  Sulfuric acid (375 g of 30% acid) was added with stiring to a mixture of 2-nitro-1-phenyl-1-propanol (54.3 g., 0.3 mole), zinc dust (90 g., 1.37 mole of 80 mesh zinc), and 100 ml of 95% ethanol.  The acid was added at such a rate that the temperature remained at 45 deg C or below.  Usually 10 to 12 hours were required.  Agitation was continued for 1-2 hours after completing the addition of acid, then after extracting the acidic solution with ether to remove non-basic materials, a large excess of sodium hydroxide (as a 50% solution) was added.  The product which was freed was extracted with ether.  Three extractions, with a total of 500 ml of ether, sufficed.  The ether solution was dried, ether was removed, and the product was distilled (b.p. 122 deg C at 4 to 5 mm); 29-32 g resulted (yield 65-70%).  The viscous liquid solidified on standing, and m. 46-50 deg C.

According to the article, "The unmethylated amino alcohol was obtained by reduction of the nitro alcohol either with zinc and sulfuric acid, tin and hydrochloric acid, sodium amalgam and acetic acid . . . Presumably many of the ordinary metal-acid reducing agents can be used provided the temperature is kept sufficiently low to prevent dehydration."
                
Then A procedure wherein phenylacetone is produced from ephedrine and its derivatives with sulfuric acid, through heating with 50-70% acid at 140-155°C in the presence of 0.02-0.5% ZnCl2 as catalyst, and the formed phenylacetone is isolated from the reaction mixture by steam distillation.

What do ya think??

cheers
 

[psyloxy]

you need nitroethane to get PPA

[Ritter]

Is it possible that reacting the 1-phenyl,1-hydroxy,2-nitro ethane produced via rxn between benzaldehyde and nitromethane as described in  the first part of this procedure with sulphuric acid will produce phenylacetaldehyde the same way ephedrine w/ H2SO4 produces P2P?  Sorry for bad english, am very hung over!

[Rhodium]

1-phenyl-1-hydroxy-2-nitroethane could undergo the Nef reaction to produce 2-phenyl-2-hydroxy-acetaldehyde, a simple reaction with sulfuric acid wouldn't do much I think.

However, if you mean the reduced compound (2-hydroxy-2-phenylethylamine), then that should be possible, but I wonder if the formed phenylacetaldehyde wouldn't polymerize its ass off in sulfuric acid?

[Aurelius]

on the topic of Phenylacetaldehyde, does anybody have the reaction conditions and workup for P. Alanine to phenylacetaldehyde with bleach?

[Aurelius]

there shouldn't be a problem using Ca(OCl)2, correct?

(assuming 1/2 the molar ratio or same number of OCl^- equivalences)

[Rhodium]

References on the Strecker degradation of amino acids to aldehydes:

http://www.geocities.com/chempen_software/reactions/RXN375.htm

Here is the procedure for tryptophan to indoleacetaldehyde. I don't think too many variables has to be changed for it to work with phenylalanine:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/indoleacetaldehyde.html

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Here are two old a.d.c posts on the subject:

I suppose my original post was a little glib when I claimed simply that phenylalanine in dilute sulfuric acid would turn ino phenylacetaldehyde,with portionwise additions of NaNO@ or lazy. Since I got some bad mail suggesting I' a spook and since the post has dissappeared, I guess i"ll try again providing contions and a little homework:

Standard organic chemistry texts that I have read give nitrosification in acetic aqueous media as a means of deamination of aromatic amines ( the product being the corresponding alcohol). The same texts stane that the reaction is of LITTLE or no utility with aliphatic amines in general, giving mixtures of alkenes and alcohols. Again, another reaction I want to point out is that of DECARBONYLATION OF ALPHA HYDROXY AMINES. Such elementary texts describe, and I quote from Noller: CHEMISTRY OF ORGANIC COMPOUNDS, Saunders, p 857, " When alpha hydroxy acids are boiled with dilute sulfuric acid, carbon monoxide and water are lost with the formation of an aldehyde, a behavior called decarbonylation. Now, dilute acid (aqueous albeit chilled with additions of NaNO2 are just the mixtures used to deaminate aromatic amines) and I am claiming that the deamination of phenylalanine that subsequently proceedes to decarbonylation to produce phenylacetaldehyde is of very good utility indeed under rather simple conditions, and if you follow my steps this claim will be born out:

TO a saturated aqueous solution of phenylalaine and some sufuric acid ( not so concentrated that the evolution of NO2 gas is too vigorous or abrupt) I added portions of NaNO2 (noxious brown gas comes off - a fume hood or other good ventilation is necessary although carbon monoxide evolution is not so vigorous as to be dangerous) it is desired that the mixture be stirred to a gentle effervescence by adding portions of NaNO2 with gentle loving care, then gradually heating to boiling as gas (NO2) evolution gets weaker,then cool and repeat. After about 20 minutes a light brownish oily residue of drops begin to separate ourt having a sweet and candy-like smell somwhat reminiscent of cinnamaldehyde. I continue adding NaNO2, stirring and heating this way untill phenylalanine is spent or I add more phenylalanineand continue as a process. If necessary add HCl to keep acidic when NaNO2 gas is no longer emitted. I have by no means perfected the process, maybe it would get better milage from the NaNO2 if I started it chilled, but the phenylacetaldehyde is fine and easily extracted from this mommie liquor with trichloroethane (god have mercy on the enviornment).

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Conceivably conditions could be found that would allow in-situ hydrolysis of the imine formed from phenylalanine to give phenylacetaldehyde would would then be further oxidized to phenylacetic acid which can then be converted to P2P and then to meth by any of the usual methods. Of course, this oxidation would stink to high heaven (phenylacetaldehyde smells even stronger than phenylacetic acid, which really smells), but it uses readily available materials. I haven't had a chance to try it out so if anyone else would like to I'd love to hear of your results (see H. L. Slates et al, J. Org. Chem., 29, p. 1424 (1964) for a starting point).

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[blondie]

another route to phenylacetaldehyde -

benzaldehyde + nitromethane --> b-nitrostyrene
b-nitrostyrene (Cr(ii)Cl catalysed nef reaction) --> phenylacetaldehyde (80%)

Post 244992

(foxy2: "Chromium(II)Chloride Reduction of Nitroalkenes", Chemistry Discourse)

[Wouter]

Does anyone know of this is possible; Henry reaction* with EtNH2 instead EtNO2? If it works it's possible to make PPA with one-reaction from BzH!!  Please let me know...

*

http://themerckindex.chemfinder.com/TheMerckIndex/NameReactions/onr182.htm

[Rhodium]

No, the henry reaction only works with nitroalkanes.