10-15-01 15:30
No 224776
Okay now i grabbed yer attention. Sure it aint elegant. But it aint byzantine either. Of course it's been covered before. Has to have been. But read on...
1.Oxidise tolulene to benzaldehyde.
C6H5CH3 ===(MnO2/ H2SO4 65%)===> C6H5CHO
2. Convert EtNO2 ===> CH3CH2NO2 (see rhodium's site. "Ethyl Nitrite...")
3. Condense benzaldehyde and nitroethane to yield
phenyl-2-nitropropene.
Now this is the step I aint sure about. You can do a length reduction with NaBH4 to the alkane, then with some other shit to the ketone, but Rhodium said in some archive posts that...
"5) The above (P2NP) is reduced with Fe/HCl to give P2P."
P2P from tolulene, ethanol, NaNO2, H2SO4, MnO2, Fe, parrafin, HCl...cmon...it's 100% OTC!
fruc
off.
Isn't Disney World just a people trap operated by a mouse?
(Official Hive Translator)
10-15-01 16:50
No 224794
Step 2 in your synthesis is still a major problem.
One of my Russian friends reported the overall yield of ~7% from the procedure with sodium ethyl sulfate from Rhodium's.
He was sloppy though. SWIM tried to repeat this and got smth more similar to 0%
He wasn't that sloppy but still was sloppy. It's hard not to bee sloppy when filtering Ca salts
.But now with a couple of patents that PolytheneSam gave me links to (deal w/easy filtering), and the proc. of getting 98% ethylsulfuric acid from 95% ethanol and H2SO4... I think that might bee a viable route. A really good one, maybee.
Interested? I'll give you more info upon request.
As for the nitrite to nitro rearangement - it pretty much sucks, i'm speaking both from SWIM's personal experience AND from the theory - it gives not more than 20% (in theory) yields - practically much less, and - did you ever actualy think of what kind of apparatus one will have to construct for doing this?
I've tried to make one, and it's actually easy with some ingenuity , but IMHO not quite worth the effort
.I strongly believe that ethylsulfate is the future, although SWIM hasn't checked it yet - has to spend all his money for college tuition
BTW - amph/meth are very addictive, one really shouldn't make them at large scale - for his own goodness's sake. Believe me, it is the wisdom.
Antoncho
(Newbee)
10-16-01 02:24
No 224984
Thanks Antoncho!!
Yeeeeesss. Ethyl nitrite route. Hmmmm. Upon review it definatelty looks a little more sour than it did at first. Working with EtNO2 is a bitch for starters. It boils at 17C, so it looks ok as soon as you take it out of the freezer, but rapidly evaporates. I had a look at the NaEtSO4 route and that looks really good! Very simple apparatus
and easy chemicals. The only problem being getting the CaSO4 out of the mess. Did you try vacuum filtering over an absorbent cotton pad? Alternativley could you not just produce the ethylsulphuric, then distill it over, leaving Excess H2SO4. Wash it with dH2O, redistill, then add produce your NaEtSO4 from a pure-ish sample? Without the need for Ca Salts?And YES i would be interested in those patents/refs that you have?
46% yield with such easy precursors is rather good. Better than 0 - 20%
. Apart from step 2 how does the rest of the synth look, particularly step 5?fruc
off.
Isn't Disney World just a people trap operated by a mouse?
(Synaptic Cleft Mountaineer)
10-16-01 03:06
No 225010
Yes, step 5 is covered on my page: ../rhodium /mdp2p.p
(Wizard Master)
10-16-01 04:42
No 225057
If you make phenyl-2-nitropropene then reduce it down to amphetamine. I don't like the reduction/hydroloysis of phenyl-2-nitropropene using Fe/HCl to P2P.
(Hive Bee)
10-16-01 11:28
No 225201
In the reaction of Beta-NitroIsoEugenol with Vanillyl Methyl Ketone as product, would a Al/Hg/MeAM yield 3-Methyl-4-Hydroxy-Meth or am I just being stupid? This is not active becuase of that damn hydroxy, so what is the purpose of this synth? I'm sure I'm missing something although the purpose of the second (MDP2P) is clearly quite useful.
What's wrong with the Fe/HCl that you say you don't like it.
One more thing, has anyone figured out if the Pseudonitrosite reaction works for IsoSaffy or are the rumors of it being an exception correct?
(Hive Addict)
10-16-01 15:01
No 225228
has anyone figured out if the Pseudonitrosite reaction works for IsoSaffy or are the rumors of it being an exception correct?
I think you might want to check out the thread starting with Post 177886 (Dr_Sister: "the POWER of pseudonitrosites!", Chemistry Discourse).
"High yeilding iso-safrole to MDP2NP pseudonitrosite proceedure
by Antibody2 02/2001
Having had a few sucessful dreams synthing TMA2 from asarone and PMA from anethole via the pseudonitrosite route, antibody was delighted to find that iso-safrole suffers from none of the yeild limiting factors suffered by either asarone, which easily polymerizes during nitration or anethole whose pseudonitrosite is difficult to hydroylse in satifactory yeilds. In two consecutive reactions with iso-safrole near quantitaive yeilds of the pseudonitrosite were formed. This pseudonitrosite is also hardier during hydolysis. The hydrolysis method outlined below is gentler than that in common usage and was inspired by a Weiland ref that Uemura came-up with and a re-read of TSII.
Nitrosation of iso-safrole
A 2l rb flask is charged with 2.5M NaNO2 (173g ) in 250mls dH2O. The flask is placed an ice bath and the NaNO2 is dissolved with mag stirring. 0.5M freshly distilled [1] iso-safrole (89g) was dissolved in 900mls diethyl ether (distilled from zerostart starting fluid). This is added to the flask. A pressure equalized dropping funnel charged with 1.25M H2SO4 in 500mls dH2O is placed in the rb flask. a hose is attached to the top of the funnel leading out of doors. After contents had been allowed time to cool. the H2SO4 solution was dripped in over 6 hours with slow mag stirring, ice being replaced as necessary. Flask was then allowed to sit for an additional 9 hours while ice was allowed to melt. During this step, a 6-7cm layer of white spongy precipitate will form at the interface of the two layers.
The dropping funnel is removed, and the reaction mixture is stoppered, and shook vigourously, with care being taken not to break flask with mag stir bar [2]. The entire contents is gravity filtered using coffee filters and a 2l gasoline funnel. The etherial layer and the the aqueous layers are saved for later [3]. The filter cake is then scraped into a 2l beaker containing 1l dH2O and stirred with a spoon for a couple minutes. What will happen is all the NaSO4 will settle at the bottom, while all the pseudonitrosite will float in suspension. The water is decanted with the suspended pseudonitrosite from the NaSO4 which can be saved for other uses if desired.
The water layer with pseudonitrosites is vacuum filtered and washed with additional dH2O. The filter cake can then be washed 2X with EtOH or more expediently the filtercake is then dropped into a beaker containing 200mls EtOH nand stirred throughly, and then vacuum filtered.
Yeild 0.49M pseudonitrosite of iso-safrole 98% (127g) as white crunchy nuggets [4]
Hydrolysis of pseudonitrosite
A 2l beaker sitting in an ice bath is charged with mixture of 0.5M KOH (28g) dissolved in 700mls EtOH. When mixture has reached 10°C the pseudonitrosite is added portionwise over 10-15 minutes with care being taken not to allow temperature to exceed 20°c. The is mag stirred vigourously until all pseudonitrosite has gone into solution. While this is stirring prepare 500mls of 2M aqueous HCl (approx 105mls 31% HCl and 395mls dH2O) and refrigerate. When all the nitrosite is in solution it was vac filtered and the filtrate returned to the ice bath and one tray of ice-cubes is added and cooled to 5°C. Then as 500mls cold dH20 is added slowly the solutions goes from an umbra to an ochre color,the chilled dilute HCl solution is added as a tiny stream to the stirring solution over 5-10 minutes. During the addition the solution becomes cloudy and most of the ice melts. The entire mixture is poured into a 4l wine jug containing 2l dH2O. And the entire mixture is refrigerated for a couple hours. During which time the the entire jug will transform into bright yellow crystal matrix, and probably a brilliant yellow bottom oil layer, which is also the nitropropene in oil form. The crystals and solution are decanted from the oil layer and vac filtered, the filtercake is dissolved in 300-400mls boiling IPA to which the yellow oil layer is also added. Agitate until all is in solution then allow to cool slowly [5] to room temperature when it may be refrigerated for an additional hour to complete recrystalization. Then vac filter, wash filter cake with dH2O, and place in a stoppered filter flask charged with silica gel and attach to low vac (fridge compressor) overnight to desicate.
Yeild 0.36M 3,4 methylenedioxy-phenyl2nitropropene 73% (80g)
as bright yellow needles the texture of compressed glass wool insulation."
Followed by some discussion and notes, then kudos, and then minor tweaks.
z
"And if we don't get some cool rules ourselves, pronto, then we'll just be bogus too!"
(Commodore "Mole Bouncer")
10-16-01 16:56
No 225256
if directions as printed (no solvent substitutions!!) are followwed, you will not be disappointed."All those memories lost like rain..."
(Hive Bee)
10-16-01 17:24
No 225266
If there is no real difference in yield, I'd like to try Nitric Acid instead. The gassing procedure takes care of that annoying Sodium Sulfate that has to be seperated.
Any ideas?
(Hive Addict)
10-16-01 20:01
No 225328
AB,
My evil twin promises decent results using your "Lowdown on Pseudonitrosites" procedure for asarone with clean toluene instead of ether...
Wonder how tol works for isosaffy???
z
"And if we don't get some cool rules ourselves, pronto, then we'll just be bogus too!"
(Commodore "Mole Bouncer")
10-17-01 17:36
No 225804
Zolligan - No Shit! i never triied toluene, i remembered in the "Low Down" somebee, maybe foxy ran into problems with toluene, so i avoided it.
I do know this, asarone is much more difficult to nitrosate than isosafrole, if it works for asarone, my guess would be that iso-safrole would work as well.
got a test tube and some iso handy? I'd like to hear the results.
Chillerb - using nitric is a lower yeilding synth from what i understand, and no one has posted an optimized proceedure as yet, i would reccomend keep her on the beathen path until, you have some confidence, then go bushwacking. If you read the old posts, you will realize that the current derigeur method took months to optimize, can you wait that long?
"All those memories lost like rain..."
(Hive Addict)
10-17-01 21:37
No 225894
No shit. I distinctly remember telling you that back when you were working with asarone. It was right before I sent you the Urushibara chapters.
Sorry to say that at the moment, I don't have any List I isosaffy lying around
. Perhaps my girlfriend's cousin's babysitter's auto mechanic does... I'll check and get back to you...z
"And if we don't get some cool rules ourselves, pronto, then we'll just be bogus too!"
(Stranger)
10-18-01 13:45
No 226210
Right what about this as an alternative for otc p2p?
1) Heat alanine (amino acid from pharmacist) and benzaldehyde (almond essence from supermarket) -> PPA + CO2
(note this is a name reaction)
Post 173131 (not existing)
2) Steam distill PPA with sulfuric acid + AlCl3 -> p2p
(covered by patent)
Post 177857 (LaBTop: "Re: DETAILED METHODS for NON-CHEMISTS The Sequel !", Newbee Forum)
What's the catch here?
Seems easy cheap, and very otc.
(Hive Bee)
10-18-01 14:24
No 226213
zooligan!
Uemura contributed in the 'low down..' thread with a small scale experiment using toluene and anthole? There was some success with the nitrosite, but the hydrolyse didn't work. So he never followed the toluene path. He agrees with ab2: use ether!!!!!!
Carpe Diem
(Hive Addict)
10-18-01 15:51
No 226246
How did you hydrolyze? 8% ethanolic KOH? Yields are not all that great but my friends got nice yellow nitropropene crystals, so bright yellow it almost hurt to look at them. Recrystallizing from warm EtOH gave needlelike translucent yellow crystals. Sorry, no m.p. data....
z
"And if we don't get some cool rules ourselves, pronto, then we'll just be bogus too!"
(Hive Bee)
10-18-01 16:19
No 226254
zooligan,
check the 'low down...' thread! Uemura really thinks he posted some infos. If you don't find anything and you need more details, PM him and he may find perhaps something useful in is lab notes.
Carpe Diem
(Stranger)
10-19-01 01:36
No 226460
Joyman, beleive that you need a base in your heating to make that work (believe it's a condesation rxn (?))
(Stranger)
10-19-01 11:05
No 226707
Aurelius,
Do you mean need a strong base for the first reaction?
Akabori, J Chem Soc Japan 64, 608 (1943)
Used n-methyl alanine and benzaldehyde to yield ephedrine.
been mentioned at the hive a couple of time
Found a German ref for the same reaction. From what i can tell (babel translated) its just a matter of controlling the temperature (139c from memory)- yeilds were ok. Really simple.
I spent a day trying to track down the japanese article at a couple of uni libraries with no luck. If anyone wanted to look this up ... (not sure if its english or japanese)
Using alanine would give ppa, distill with h2so4 -> p2p
I can by the inputs in kilos.
(Stranger)
10-19-01 13:05
No 226730
Name Reaction
http://www.pmf.ukim.edu.mk/PMF/Chemistry
I think this is pretty.
(Hive Addict)
10-19-01 14:42
No 226746
Uemura really thinks he posted some infos.
I was just asking because my evil twin had no probs at all with 8% KOH/EtOH. Had to stir and heat a bit, but it turned out fine. Rextallization gave translucent yellow needles..
z
"And if we don't get some cool rules ourselves, pronto, then we'll just be bogus too!"
(Stranger)
10-19-01 22:43
No 226873
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.
(Wizard Master)
10-20-01 04:29
No 226998
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
(Stranger)
10-20-01 09:32
No 227070
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.
(Distinctive Doe)
10-22-01 21:31
No 227827
(Rated as: excellent)
If someone can get the details out of these article it would bee really nice!
Stereospecific synthesis of α-amino-β-hydroxy acids
J. Org. Chem. 44, 3967-9 (1979)
Reaction between aromatic aldehydes and α-amino acids. I. New facts on the Akabori reaction.
Takagi, Eiichi.
J. Pharm. Soc. Japan (1951), 71 648-51.
Abstract
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-methyl
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.
Abstract
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-metho
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.
Abstract
N,O-Dimethylserine was refluxed 25 min. with benzaldehyde in pyridine to yield 48% 1-phenyl-2-methylamino-3-methoxy-1-propa
In the following article they produce the following, which could be decarboxylated to something useful.
1,3-Benzodioxole-5-propanoic acid, α-amino-α-ethyl-β-hydroxy
and
Phenylalanine, β-hydroxy-α-methyl-, methyl ester, hydrochloride
Synthesis of amino acids and related compounds. 3.
Stereoselective syntheses of α-alkyl-β-hydroxy amino acids.
Chem. Ind. (London) (1973), No. 5 228-9.
Abstract
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 α-alkyl-β-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.
(Hive Addict)
10-23-01 18:14
No 228053
I found ../rhodium /isosafr
Ideas??
z
"And if we don't get some cool rules ourselves, pronto, then we'll just be bogus too!"
(Stoni's sexual toy)
10-26-01 15:07
No 229023
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).
(Hive Addict)
10-26-01 20:27
No 229089
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??
z
"And if we don't get some cool rules ourselves, pronto, then we'll just be bogus too!"
(Hive Bee)
10-29-01 01:40
No 229711
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.
(Master Searcher)
11-20-01 03:17
No 238521
See Post 229056 (not existing) . How about PPA --> N-methyl derivative using this method? Post 178931 (PolytheneSam: "PPA --> meth this easy?", Chemistry Discourse) Maybe there are other ways to hydrogenate the intermediate.
http://www.geocities.com/dritte123/PSPF.
(Distinctive Doe)
12-06-01 19:09
No 244992
(Rated as: excellent)
CHROMIUM(II) CHLORIDE REDUCTION OF a,b-UNSATURATED NITROALKENES.
A FACILE ROUTE TO CARBONYL COMPOUNDS.
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.
TABLE I: CARBONYL COMPOUNDS FROM NITROALKENES VIA CHROMIUM(II) CHLORIDE REDUCTION
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
(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.
REFERENCES AND NOTES
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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