Chloramphenicol to amphetamine

[Tsathoggua]

Ho hum...I just looked at the structure of chloramphenicol, and hey, a hoffman degredation of the acetamide group through its intermediate isocyanate in aqueous medium, protection of the resulting N-methyl amine followed reduction of the nitro to an amine, then deamination of the aryl amine group with HNO2 in situ from NaNO2 and dilute H2SO4, deprotection then reduction of the two remaining hydroxyl groups on the sidechain with the classical hydriodic acid route of choice in 2x molar amount, and what do you get? damned near OTC amphetamine.

Wonder what an amphetamine carbamate would do, come to think of it, by doing the above and reacting the formed isocyanate from the hoffman in alcohol of choice. Muscle relaxant amphetamine hybrid? of course protecting the carbamate from getting arseraped by HI would be nescessary.

Will the hoffman degradation work for a secondary amine? if not, then amide reduction with diborane, LAH, or probably borohydride, hydrogenation with Pd/C to the N-ethylamphetamine would be even sweeter, its less neurotoxic than meth, smoother than either meth or amphetamine, and has less potency than meth, but greatly more so than unsubstituted amphetamine.

Idea is on the table, lets hear some discussion and critique of the idea.

Wasps and Bees, get your stingers at the ready, on yer marks, get ready, stick it full of holes. 

[Tsathoggua]

Orally, yes its almost unavailable.

OTC as eyedrops here in the UK.

And not really for practical business use, as a rxn scheme, more for lab experience and fun value for personal interest and personal use.

[zzhuchila_clocker]

a hoffman degredation of the acetamide group through its intermediate isocyanate in aqueous medium, protection of the resulting N-methyl amine

substituted methylamides do not undergo hoffman rearr-ment. the mechanism of isocyanate formation (how it can have more then 1 nitrogen substituent then) includes deprotonation of RCONHCl to RCONCl-, elimination of Cl- to give acylnitrene RCO-N: which rearranges to isocyanate then. So, chloramphenicol or another acyl derivative would not react as the chloroamide lacks a hydrogen atom.. Better to hydrolyse acyl group and protect amine with formylation, and after HCl or HBr substituting both OH groups treat it with LiAlH4, it should reduce both halogens and formyl group to give meth

[headstrong]

I'm working on this antibiotic as well, freely flow in my place no prescription needed and very cheap. But my target synthesis is para nitro amphetamine or para fluoro amphetamine. Seem like this one is a good precursor to para nitro amphetamine, without going to amphetamine. And to para fluoro amphetamine, better than buying 4-fluorobenzaldehyde that is very expensive.
I plant to;
- acid/base hydrolysis
- reduce NO2 to amine
- reduce 2 hydroxyl group.
- modify NH2 (para position) to fluoro or nitro (how to convert it to nitro without effecting the amino alkane?)
Not as easy as i thought, any idea?

[zzhuchila_clocker]

how to convert it to nitro without effecting the amino alkane?

i think you first need to protect side chain amino group in the presence of aromatic one. (i don't know how but i think it shold be possible since they differ in reactivity but hopefully these should be an OTC protecting group). How are you going to reduce both OH groups? - it should be tricky, especially the terminal one.  I suppose it is better to get rid of it by means of elimination. Oxidize the benzylic position to keto- by a mild oxidizer, then this substance would be easily converted to p-X-C6H4-CO-CO-CH3, this may require heat, or acid, or even base to promote the elimination (first you get X-C6H4-CO-C(NHR)=CH2, which is readily hydrolysed). Then you can: reduce both keto-groups to diol and rearrange it to P2P in the presence of acid. Or you can reductively aminate it to get (if i'm not mistaken, that would be a major product) - a-amino(maybe substituted)propiophenone, or a ephedrine/pseudo derivative. Then you can make some sort of cyclic urea derivative or MAR
Besides, i'm very surprized of how chloramphenicol would behave under meerwein-ponndorf reaction conditions with aluminium isopropoxide and acetone. In theory a variety of products can be formed, but in fact major would be only one. As benzylic position is more prone to oxidation, but at the same time more sterically hindered in this compound's case, you may get either propiophenone or b-phenylpropionic aldehyde derivative, which can eliminate water and end up either as a-ketopropiophenone or a-keto-b-phenylpropionic aldehyde. These ketones should be thermodinamically not that favored and reduced with isopropanol(that is formed in equilibrium) back. In one case we would get a useless PhCH2CHOHCH2OH or its ketonic derivative while in another this would be PhCOCHOHCH3, or a diol or PAC. I'm still not sure about conditions needed for elimination, and there is no possibility to drop acid there since it will kill the aluminium alkoxide catalyst. Strong base is also not a very good choice because it will cause self-condensation of acetone. Maybe some amine, ammonium salt or metal ions would do as they can form chelates with chloramphenicol and ease the abstraction of alpha-proton like it happens in copper chelate of glycine that is used to produce threonine by aldol reaction with acetic aldehyde, and here it is elimination of OH opposed to carbonyl group attack
Don't consider it as a practical guideline- this is just a theoretical proposal. But without them this Science may become equally dead
And oxidation aminogroup to nitro is a well known reaction, can be made by one of reagents below

[Tsathoggua]

4-nitroamphetamine has the potential to be dangerous, it (the nitro group is a pseudohalide and will possibly mimic a halogen, afaik ONLY the para-fluoro and possibly para-trifluoroalkyl groups as far as halides go) may be a potent serotonergic neurotoxin in a similar manner to para-chloroamphetamine/PBA/PIA.

Wouldn't touch it with a bargepole.

[zzhuchila_clocker]

btw, after oxidizing benzylic group to keto, the p- nitro group can be substituted to alkoxy, hydroxy, etc(i'm quite sure). did not get refs now, but if i come across once again i will provide.

[headstrong]

Thanks, i'll do research to any point you posted, before i give any comment.

When i try to do base hydrolysis, solution become dark red, polymerization i think, and it should be cause of the nitro arene group, weird.

the p- nitro group can be substituted to alkoxy, hydroxy, etc(i'm quite sure).

This true, many way are available, i read in some chem books but i'm forget which books, many should be available in this book; Comprehensive organic transformations_2ed_1999-Larock.

And for any of you that hard to find this one, there's a chloramphenicol analog that is thiamphenicol, it uses as veterinary antibiotic, maybe it easy to find, cheap and can be obtained in bulk.

[zzhuchila_clocker]

When i try to do base hydrolysis, solution become dark red, polymerization i think, and it should be cause of the nitro arene group, weird.

interesting! did it become dark red immediately, or after prolonged time? If immediately, this is probably because of impurities(what is a content of that brand of chloramphenicol u used, or it was pure?)
My other guesses are:
- formation of arene anionic sigma complex: the terminal alcoholate attacked the p-position to nitro group with formation of a 5-membered cycle and phenyl delocalized anion, but i'm not sure if it has strong colour    
- due to oxidation of side chain by air oxygen and further polymerization that gives a system of double bonds conjugated to benzene ring that causes colour. Otherwise, usual 1,3-dihidroxy2-acylamino compound could not cause colour even if oxidized. Phenyl ring could also promote the oxidation by making a benzylic position (adjacent) more prone to it then in case of plain propane.
- due to proton abstraction and elimination of acylamide group: nitro group makes the benzylic hydrogen more acidic, and it can be abstracted by base. Then the neighbouring NHAc group eliminates with formation of b-hydroxypropiophenone derivative which is a ketone and can self-condense
- due to cyclization to pyrrole that was further oxidized: the benzylic carboanion formed by a base proton abstraction attacks the CCl2 or more likely CO group formed by base treatment, that leads to a pyrrolidone ring, and then elimination of water leads to 1,2-dihidroxy-3-(p-nitrophenyl)-4-hydroxymethyl pirrole, that can be oxidized, self-condensed, and colour can probably emerge after a single electron oxidation to radical
Anyway, i don't know if at least one of this explanations can be possile, but i really don't have any other idea of what happened.. As for posymerization of this particular compound(chloramphenicol) - it does not polymerize, and nitro group itself can not be a reason because it also is inert (both to polymerization and oxidation). The problmes with polymerization can occur after the side chain is transformed to smth having carbonyl, double bond etc. Oxidation - after a formation of double bond. The above explanations were my attempt to theorize how a double bond or carbonyl or smth else could be formed with possibility to further polymerize
By the way, i'm not very positive but the hydrolysis may be possibly promoted by CuSO4. Copper will form a chelate with either amino or carbonyl group and one of hydroxyls, that will be hydrolysed more easily(i've done this with ethylsalicylate once, it can be easily stored as a Na salt in water-alcohol solution in the presence of excess base for some time without hydrolysis, but after i added CuSO4 the copper chelate was hydrolysed to salycilic acid that formed a copper(or along with sodium) salt precepitate after some time of storage.
If that colour reaction was not due to content, try to avoid air access next time, you can also drop ascorbic acid there it will not allow the substance to oxidize, it will oxidize itstead, but copper should be avoided then as it will also form a complex with ascorbic  

[headstrong]

I get it from pharmacy, I did it twice,
-first i used water and NaOH, Chloramphenicol solubility in water is very bad, so many of it was undissolved, the solution become red after heat to 80 c in few minutes, 2 hours latter solution become like blood dark red, some is become like gum.
I thought it caused of ether polymer, alkyl chloride and hydroxyl group, so in 2nd experiment  i tried to make it as a solute before heating.

-2nd,
1.dissolve chloramphenicol in some EtOH,
2.add some water (exothermic), heat to 80 c for 1 hour, the color wasn't changed.
3.Add NaOH
4. reflux for 4 hours, the color has been changed to red after minutes and gradually become darker, finally dark red but no gum maybe (the gum is dissolved).

Reading you said about cyclic compound make me remember there's a paper about isoeugenol that easily react with acid and Lewis acid resulting cyclic compounds, may be it also happen to allyl benzene and to chloramphenicol in different ways.
Merc index stating Chloramphenicol is stable in hot acid solution, maybe what they mean "stable" is related to cyclation and not to hydrolysis.

Surprisingly i just found an Amphetamine synthesis paper very related to this substance in Rhodium archive, i never expect it.  You can find it in (Meth)amphetamine section under title An Efficient Synthesis of (S)-(+)-Amphetamine from (1S,2S)-2-Amino-1-Phenyl-1,3-Propanediol
I Think Rhodium archive is available here, but i don't know where.
 

[zzhuchila_clocker]

I thought it caused of ether polymer, alkyl chloride and hydroxyl group, so in 2nd experiment  i tried to make it as a solute before heating.

maybe, but i suppose OH- would react with alkylchloride at a faster rate, at least if it is a bimolecular reaction. even if polymer forms, it won't have such colour..

I get it from pharmacy

but was it a pure substance or it is in tabblets? see the contents of tablets then, this red thing may be cause to some else compound. did it dissolve in EtOH completely? Otherwise, the difference in gum formation that you observed between alcoholic and water hydrolysis could be due to admixtures that could not disssolve in ethanol ant the gum was not formed. Or this gum could be just soluble in water-ethanol solution and insoluble in water, if you distill off ethanol from second exp you can see if it precepitates. Btw, if it is a sludge rather then _gum_, it can be just unreacted chlormphenicol or hydrolysed product(btw is it soluble in ethanol, acetone etc?).
As for cyclic compound, i think it was not the same type as in safrole lewis acid treatment, or chloramphenicol resistant to acid(cycle formation would mean it is not inert to acid)
I mean it could be a http://en.wikipedia.org/wiki/Meisenheimer_complex . And because it is intramolecular, even one nitrogroup could be sufficient to make it form in equilibrium(not sure). Anyway, it was only a propose. Here is an interesting article about such complexes, some are even stable in solid state http://www.mdpi.com/1420-3049/13/6/1282/pdf. Still i think it was not a complex, because it should have formed immediately. Few minutes means it was not a proton abstraction/addition but some other reaction. Btw, you can easily establish if this was a complex by acidification of smaller part of your solution both in the beginning (after initial colour formation) and in the end of reaction. If colour dissapears, then it was complex. Also you can add there ascorbic acid in basic solution in order to know wether the colour was caused by some anion-radicals, as they may also become colourless on addition of acid.  Otherwise, when you next time go to pharmacy try to purchase there some ascorbic acid (if it is sold in your area). It would help to see, if this colour is due to oxidation or not
As for rhodium amphetamine synthesis, if i am not mistaken it uses such reagents as HI and then LiAlH4 to reduce the terminal iodide formed. Not that convenient

[zzhuchila_clocker]

By the way, Merck index lies! So you can do same and avoid many side reactions with base
(the picture is from http://pubs.acs.org/doi/abs/10.1021/ac60041a006)

[headstrong]

It comes as capsule, 250 mg, but i found 260 mg each (without capsule), just a little inactives. When i performed experiment 2nd i dissolved in 95% EtOH a little is insoluble, have been filtered before heating, i'm sure this not caused by inactives.

maybe, but i suppose OH- would react with alkylchloride at a faster rate, at least if it is a bimolecular reaction. even if polymer forms, it won't have such colour.

That it's, you can imagine they will easily be polymerized if no solvent is used, and as i said many is insoluble in experiment 1th. Then in 2nd experiment they still become dark red, but i think the thickness is far different, 1st solution much thicker. Means there are 2 (or more?) unexpected products, ether polymer and "x" substance that i believe come from nitroarene. So in 3th i'll try to do acid (HCl) hydrlysis and 4th reduce NO2 to NH2 then base hydrolysis.

As for rhodium amphetamine synthesis, if i am not mistaken it uses such reagents as HI and then LiAlH4 to reduce the terminal iodide formed. Not that convenient

Yes nothing new there, but it still surprising me, how come that chief bee place it in the archive
And i only have very common chemicals, something like NaBH4 or LAH are far away from me. Alcohol reduction i plan to use old HI/H3PO3 route or Halogenation by HI then reducing by Sulfite if isolation to di iodo sunstance is possible.

By the way, Merck index lies! So you can do same and avoid many side reactions with base
(the picture is from http://pubs.acs.org/doi/abs/10.1021/ac60041a006)

Too bad i don't have access to get full paper, but i'll try to find it, thanks.

[embezzler]

Polarographic Estimation of Chloroamphenicol (Chloromycetin)

Geln B. Hess

Analytical Chemistry
pp 649–651
Vol 22 (5)
DOI: 10.1021/ac60041a006

A  polarographic method for the estiniation of chloramphenicol (Chloroniycetin)
is presented.  The reduction of chloramphenicol and of  its hydrolysis  product,
l-p-nitrophenyl-2-amino-1,3-propanediol,  at  the  dropping mercury  electrode
has  been  studied  at  various  pH  values  and  the analysis of  the polarographic
waves is given.  The reaction is irreversible and  involves four electrons  in the first wave,  indicating preliminary reduction of  the nitro group to the hydroxylamine.

[zzhuchila_clocker]

The polymerization in solid state is next to impossible, only if the sustance is melted, or hygroscopic enough to melt at lower temp because of water/other admixtures. So, only if the undissolved chloramphenicol was liquid (it should melt at about 130) due to some reason it can react with something, otherwise - not a slight reaction, despite it is "concentrated" on the bottom, will occur.
I think if you evaporate ethanol from your 2nd experiment the same thing would precepitate, or add ethanol in 1 to see if sludge dissolves(or don't do that since you are going to use acidic hydrolysis

Alcohol reduction i plan to use old HI/H3PO3 route or Halogenation by HI then reducing by Sulfite if isolation to di iodo sunstance is possible.

HI will reduce one position so you would isolate mono-iodo. Do you think sulfite will reduce a iodoalkane? Rhodium's route would not have used LAH for that then.  Or you want to use it for NO2?

[Wizard X]

Chloramphenicol formulations. http://en.wikipedia.org/wiki/Chloramphenicol#Formulations

In some countries, chloramphenicol is sold as chloramphenicol palmitate ester. Chloramphenicol palmitate ester is inactive, and is hydrolysed to active chloramphenicol in the small intestine. There is no difference in bioavailability between chloramphenicol and chloramphenicol palmitate.

The intravenous (IV) preparation of chloramphenicol is the succinate ester, because pure chloramphenicol does not dissolve in water.


Preparation Instructions. http://www.sigmaaldrich.com/etc/medialib/docs/Sigma/Product_Information_Sheet/c7795pis.Par.0001.File.tmp/c7795pis.pdf

This product is soluble in ethanol (50 mg/ml).  This product is also very soluble in butanol, acetone, and ethyl acetate; slightly soluble in water (2.5 mg/ml); and
insoluble in benzene, petroleum ether, and vegetable oils.

[headstrong]

@Embezzler, thanks

The polymerization in solid state is next to impossible, only if the sustance is melted, or hygroscopic enough to melt at lower temp because of water/other admixtures. So, only if the undissolved chloramphenicol was liquid (it should melt at about 130) due to some reason it can react with something, otherwise - not a slight reaction, despite it is "concentrated" on the bottom, will occur.

It slightly soluble in water, solubility should be increased when temperature is increased, imagine about local hypertension. There are many spot in which Chloramphenicol concentration is much higher, surely ether will be produced there, and what i mean with polymerization is more than one molecule combine into one, and not refer only to macro molecule.

due to some reason it can react with something, otherwise - not a slight reaction

If you think about pills inactives i say no, none of pills inactives can do that, and none of pills gum PEG, PVP,... and various eudragit, PEG is alcohol, PVP is ketone, eudragits are ester and in the hydrolysis sistem will serve carbocylic acid, alcohol, and amino alcohol, none of inactives functional group more reactive than what are in chloramphenicol.
PVP more possible than other but you can easily determine how much surfactan containing when you dissolve it in EtOH with some smooth powder (already exist in mine), if there is no stable emulsion mean no surfactant or trace. No stable emulsion was occured in my experiment.

HI will reduce one position so you would isolate mono-iodo.

NO, HI/H3PO3 (and other like HI/redP and I2/H3PO2,...) will reduce both primary alkyl alcohol and secondary benzylic alcohol.
The trouble is not the ability of HI to reduce primary alcohol, but in HI reduction of AMINO Alcohol if the reduction rate is much slower then halogenation means trouble, you will get many by product. This will be happened here, surely it because of primary alcohol.

That why (as i said) another plan is halogenation by HI into di iodo follow by reduction by sulfite if.....

Do you think sulfite will reduce a iodoalkane?

YES.
But i don't know yet what kind of inorganic sulfur sodium sulfite, dithionite,...And to primary iodo alkane still a question, don't find yet. To primary aliphatic alcohol, honestly i just HOPE the answer will be yes
I think the problem in alkyl iodide reduction by sulfite is the solvent, and water isn't really suitable.  

Rhodium's route would not have used LAH for that then.  Cheesy

Many milder route are available, you doesn't have to use LAH to reduce primary iodo alkane, various low valent metal procedures,....

i think you first need to protect side chain amino group in the presence of aromatic one. (i don't know how but i think it shold be possible since they differ in reactivity but hopefully these should be an OTC protecting group).

I just re read your previous post, at this part i got an idea how if we do something to chloramphenicol before hydrolysis, it's an amide means the amine is already protected. What do you think?

[zzhuchila_clocker]

Concerning the residue in 1st exp: my point was, that while it is solid it is quite inert to any reactions, including polymerisation. If you take citric acid and mix it with NaHCO3, both solids, what happens? Right, nothing. When you add an alkane solvent what would happen? Also nothing - the residue would be on the bottom, and we can not say there is a high concentration of citric acid and bicarbonate there even in solution that surrounds residue, because this concentration wold be close to 0. The reaction will not proceed, unless you press this in a tablet form, dry it and throw into water, or simply change alkane to water.
If such immediate reaction like acid+carbonate does not go, then how do you think polymerization would? It would also not be possible until either of points: 1) there is substantial solubility of substance(and in this case reaction will be in solution, not in the solid, and in your case boiling water would serve as a sufficient stirring for making the upper solution always saturated, same as solution that is nearby the residue) 2) the substance is molten 3) the substance forms an emulsion (solubilized) by some emulsion stabilizer like additional surfacant(as you said it was not present), deprotonated alcohol(would not be in water at high conc) 4) you use a phase transfer catalyst.
If in your case nothing of this was observed, the residue would be practically inert.

NO, HI/H3PO3 (and other like HI/redP and I2/H3PO2,...) will reduce both primary alkyl alcohol and secondary benzylic alcohol.

This is what you want to be the case. Please look here (the Java's post with big pic) http://127.0.0.1/talk/index.php/topic,378.60.html

but in HI reduction of AMINO Alcohol if the reduction rate is much slower then halogenation means trouble, you will get many by product. This will be happened here, surely it because of primary alcohol.

what kind of byproduct? aziridine? according to Java's post, it is not formed much in reaction. But if you will try to isolate iodoamine as a base or simply basify a solution it can form. Here you should probably do reduction without hydrolysis of chlormphenicol, then acyl will protect aminogroup from aziridine formation. Still, if formed aziridine can be reduced then to amphetamine easier then using LAH, it can be a solution for reduction of  iodoalkane

That why (as i said) another plan is halogenation by HI into di iodo follow by reduction by sulfite if.....

there is practically no difference between H3PO2/HI, P/HI and HI. Actual reductant is HI, H3PO2 is just recycling it reducing I2 formed in HI alcohol reduction. So you will get mostly same iodopropane

Do you think sulfite will reduce a iodoalkane?
YES.
But i don't know yet what kind of inorganic sulfur sodium sulfite, dithionite,...And to primary iodo alkane still a question, don't find yet. To primary aliphatic alcohol, honestly i just HOPE the answer will be yes
I think the problem in alkyl iodide reduction by sulfite is the solvent, and water isn't really suitable.  

Reducing iodoalkanes to alkanes with such reductants is promissing. But don't you confuse it with reduction of iodine(I2)? Do you have any refs? If not, then the problem is not solvent, the problem is mechanism. The reaction of sulfite with iodoalkane to get alkane and sulfate is energetically favorable, and thermodinamically possible, but good solubility of both reagents is not sufficient for reaction to preceed. Kinetics is also important. Each mechanism of reaction is having different energy threshold that molecules should overcome to make reaction go, and this threshold determines the reaction rate. In case of hypothetic reaction RI + Na2SO3 + NaOH = RH + NaI + Na2SO4 the heat will be released, but that is not sufficient thing for reaction to occur. You may suggest many(infinite number) of mechanisms how it can proceed with or without catalyst, but most of the routes would require so high activation energy, that reaction would not proceed during millions of years. More likely, you would have a simple nucleophilic substitution, like RI + Na2SO3 = RSO3Na + NaI or with NaOH to give alcohol despite the heat evaluation would be much less then in reduction to alkane. Thats because SN2 pathway is having lower energy threshold. So you need to find a route that would have a low activation energy. That is usually achieved by using catalysts, they participate in reaction changing the route and reducing the activation energy, but remaining unchanged after a catalytic cycle. Otherwise as Nicodem from sciencemadness wrote: "if you try to rely on thermodynamics in organic synthesis you get nowhere"...

Many milder route are available, you doesn't have to use LAH to reduce primary iodo alkane, various low valent metal procedures,....

If you know some that avoid NaBH4, LAH and Ni raney then its fine, otherwise.. What about those low valent metal procedures? If that is not palladium, and if you have/come accross a refference - i would be very pleased if you provide it

As for protecting amino group, i was saying that concerning oxidation of aromatic amino group(after reduction) back to nitro. Aslo you should use protection for reaction of aromatic aminogroup with NaNO2/HCl. I think you can use the existing one for both reactions, besides amides are better crystallized than amines, so purification would be easier. You only need to be sure, will it remain as CHCl2CO in all reactions, or it would somewhere(like basic solution) become CHO-CO, and this hydrolysis should preferably be either avoided or being quantitative that you will get only one substance in the end, not a mixture, otherwise you will not be able to crystallize it and know the yield. Besides as i proposed it can probably persist even through HI reduction(not sure). I would suggest you not to experiment with existing protecting group, or make it in a small scale.. Better find a convenient route to reduce primary iodoalkane (to alkane, or any other route) first and then anything else.

[headstrong]

If you take citric acid and mix it with NaHCO3, both solids, what happens? Right, nothing.

If you take H2SO4(l) and mix it with NaHCO3(solid) what happens?
As i said chloramphenicol is slightly soluble in water and more in hot water. Put in simple mix chloramphenicol, NaOH and a little water till sluggish, then heat till melted you will get more ether, more water resulting less ether. What else?

This is what you want to be the case. Please look here (the Java's post with big pic)

Actually YESSS! HI/P system reduces all alcohols, some phenol and in harsh condition it can reduce carbocylic acid. So, i was sure HI/P will reduce that primary alcohol.
Damn...is it that slow, 24 hours yielding trace alkane? Hard to believe this one, in other side i believe what java posted is not a joke.

what kind of byproduct? aziridine? according to Java's post, it is not formed much in reaction.

Aziridine and dimmer, after certain point of ratio (says HI : diol = 4 : 1) then increasing the amount of HI won't effect rxn rate but resulting less by product that is dimmer. Aziridine is formed depend on temperature.
And for primary alkyl Iodide reduction rate, slower resulting more aziridine and dimer.

But if you will try to isolate iodoamine as a base or simply basify a solution it can form.

(one of) What i mean with "if isolation is possible" is how many organic iodide will be converted to alcohol if i do that? It's really a question, as i know organic I easily displaced by OH-, and not meaning to debate you. 

simply basify a solution it can form. Here you should probably do reduction without hydrolysis of chlormphenicol, then acyl will protect aminogroup from aziridine formation. Still, if formed aziridine can be reduced then to amphetamine easier then using LAH, it can be a solution for reduction of  iodoalkane

simply basify a solution it can form. Here you should probably do reduction without hydrolysis of chlormphenicol, then acyl will protect aminogroup from aziridine formation. Still, if formed aziridine can be reduced then to amphetamine easier then using LAH, it can be a solution for reduction of  iodoalkane

If aziridine can be formed in this condition (when basify) means problem, because (i think) the rate of hydroxylation is faster.

there is practically no difference between H3PO2/HI, P/HI and HI. Actual reductant is HI, H3PO2 is just recycling it reducing I2 formed in HI alcohol reduction. So you will get mostly same iodopropane

NO, they are completely different, secondary benzylic alcohol run I2(HI)/H3PO3 below 100 c, 12 hrs, no reduction occured, trace alkane if lucky. Run I2(HI)/H3PO2, 90 c , 12 hrs, reduction completed, a little alcohol if lucky.
Because H3PO2 is stronger than HI itself to reduce R-I to R-H.

The reaction of sulfite with iodoalkane to get alkane and sulfate is energetically favorable, and thermodinamically possible, but good solubility of both reagents is not sufficient for reaction to preceed. Kinetics is also important. Each mechanism of reaction is having different energy threshold that molecules should overcome to make reaction go, and this threshold determines the reaction rate.

Those are too complicated for me, not meaning to poke you, but in real meaning i don't understand. What was in mind when i said sulfite can reduce...but to primary one i just hope; i ever read sulfite can reduce alkyl iodide (as i remember it's not primary), i'll looking for that reference.

What about those low valent metal procedures? If that is not palladium, and if you have/come accross a refference - i would be very pleased if you provide it

Mm...IIRC...zinc acetic acid system, this part i can find for you. I'll do that tomorrow, now i've got headache.
Anyway how come i did argumentation with you? I think it because of you, but you must think the otherwise.

[zzhuchila_clocker]

Hey, no problem, i just was trying to make your route from chloramphenicol work, and save you from some useless experiments like reduction of both iodines without autoclave, or the terminal one with sulfite. Thanks for pointing out that HI and HI/H3PO2 reductants are different, and for Zn/acetic acid reduction. Also for this, if you can find a refference "i ever read sulfite can reduce alkyl iodide (as i remember it's not primary)".
If you got headacke and still insist on calling this argumentation - sorry, i would no more do it. Just be sure that this headacke was due to personally me and not caused by simple increase of brain activity..

heat till melted

if it melted then its possible. i did not know it was melted.

If aziridine can be formed in this condition (when basify) means problem, because (i think) the rate of hydroxylation is faster.

i'm sure aziridine would form fasted then alcohol, because it is intramolecular reaction. Better to see experimental of Java's paper, they should have isolated this 2-iodoamine, maybe it is quite stable