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Picric-A
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I know you can use Sodium chlorite to oxidise alcohols but has anyone every used Sodium Chlorate?
Is it even possible? Sodium chlorate is a strong oxidising agent so i would think it would be possible...
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UnintentionalChaos
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I need to construct a terminal E-bromoalkene at the end of a medium length hydrocarbon chain (with a cyclic acetal at the far end). I can put a
halide, amine, or alcohol on the terminal position of the original hydrocarbon chain pretty easily, so any could be starting points. I could even use
a different starting compound if a decarboxylation is necessary somewhere.
Department of Redundancy Department - Now with paperwork!
'In organic synthesis, we call decomposition products "crap", however this is not a IUPAC approved nomenclature.' -Nicodem
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Nicodem
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| Quote: | Originally posted by UnintentionalChaos
I need to construct a terminal E-bromoalkene at the end of a medium length hydrocarbon chain (with a cyclic acetal at the far end). I can put a
halide, amine, or alcohol on the terminal position of the original hydrocarbon chain pretty easily, so any could be starting points. I could even use
a different starting compound if a decarboxylation is necessary somewhere. |
You did not explain if you want to make the end compound by homologating the starting one, like this:
R-CH2CH2-Y => R-CH2CH=CHBr
or by modifying the end group like this:
R-CH2CH2-Y => R-CH=CHBr
If the first is an possibility then you can take your OH terminated starting compound, do a Swern oxidation to the aldehyde and then a Wittig reaction
with CH2Br2 derived Wittig reagent. The problem is that using this specific reagent some references claim the (Z)-product as the major while other
claim the (E)-product as the major one. It might be substrate dependend, but Wittig reactions in general tend to give more of the Z diastereoisomer
anyway.
Else, you can do a Takai olefination on the aldehyde instead of the Wittig. The reaction works fine even on fragile substrates, so I your acetal protection on the
other side should withstand without problems (just check on what complex substrate it can be used successfully: Organic Letters, 8 (2006) 6039-6042).
It also has a very great E selectivity as opposed to the Wittig which tends to give more of the (Z)-product.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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497
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Two questions:
Does anyone know a good way of separating 4-methoxyphenol and 1,4-dimethoxybenzene? Or even an easy way to tell them apart? Hopefully other than
(vacuum?) fractional distillation?
Does anyone have experience with using trimethylglycine to methylate phenols? I'm really wondering if it will methylate something like hydroquinone
fully to 1,4 dimethoxybenzene or stop at 4-methoxyphenol? I haven't found any information other than the one page from the Hive.
[Edited on 21-11-2008 by 497]
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Klute
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Well, a basic wash will remove all the phenol. Also, IIRC, dimethoxybenzene is pretty volatil with steam while p-MeO-Phenol isn't.
Trimethylglycine doesn't seem very appealling. I would rather go with trimethylphosphate or ethylsulfonate/tosyl methyl esters.
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
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UnintentionalChaos
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| Quote: | Originally posted by Nicodem
You did not explain if you want to make the end compound by homologating the starting one, like this:
R-CH2CH2-Y => R-CH2CH=CHBr
or by modifying the end group like this:
R-CH2CH2-Y => R-CH=CHBr
If the first is an possibility then you can take your OH terminated starting compound, do a Swern oxidation to the aldehyde and then a Wittig reaction
with CH2Br2 derived Wittig reagent. The problem is that using this specific reagent some references claim the (Z)-product as the major while other
claim the (E)-product as the major one. It might be substrate dependend, but Wittig reactions in general tend to give more of the Z diastereoisomer
anyway.
Else, you can do a Takai olefination on the aldehyde instead of the Wittig. The reaction works fine even on fragile substrates, so I your acetal protection on the
other side should withstand without problems (just check on what complex substrate it can be used successfully: Organic Letters, 8 (2006) 6039-6042).
It also has a very great E selectivity as opposed to the Wittig which tends to give more of the (Z)-product. |
I was hoping to avoid the schlosser modified wittig reaction in favor of a vinyl hailde- alkyl halide coupling using a lithium diorganocopper (Gilman
reagent) for making the final product. I need to couple with cheap-as-dirt isopropyl bromide for the diorganocopper, whereas the schlosser modified
wittig is very reagent heavy and I'd need isobutyraldehyde to get the double bond in the right spot.
The fact that that reaction lengthens the chain is even better since I can start with poly-caprolactone plastic and not have to extend the chain after
hydrolysis (or make cycloheptanone and do a baeyer villager oxidation)
Do you think a nitrile would withstand attack by the lithium diorganocopper, because that would be an easier and even more convenient protecting group
than an acetal followed by mild oxidation at the end (silver (I) or hypoiodite). It needs to be a carboxylate at the end of the day anyway
[Edited on 11-21-08 by UnintentionalChaos]
Department of Redundancy Department - Now with paperwork!
'In organic synthesis, we call decomposition products "crap", however this is not a IUPAC approved nomenclature.' -Nicodem
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497
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| Quote: |
Trimethylglycine doesn't seem very appealling. I would rather go with trimethylphosphate or ethylsulfonate/tosyl methyl esters.
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Yes I agree, but I was hoping it would be usable because I can get it pure for $30 per kilogram OTC. I haven't seen any alternative that can be bought
nearly that easily and cheaply, much more effort involved with preparing them..
Also it occurred to me that it might work better to methylate 4-MeOphenol directly instead of HQ, since it can be easily prepared via the
H2SO4/MeOH/HQ/BQ route.
Edit:
Another question:
I'm confused about the paper found here, does it ever actually tell how much of the various dihydroxybenzenes are put through the catalyst tube? Am I missing something? It gives all
kinds of other information, but no hint of an actual quantity, at least that I can see.
It does look like an interesting alternative to conventional methylating agents. 400*C with a Cs2O catalyst isn't too bad either.
[Edited on 22-11-2008 by 497]
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Klute
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Well, it could be worth a try, I must admit I was pretty sceptical with TMP at first, especially the solventless >150°C method, and it worked
great afterall.
How would you react the two solids? As a solution/suspension in DMF or similar?
For the article, I'm under the impression that the amount of solution introduced is based on how much the 18mL/H of N2 can vaporize. Not really a
preparaitive procedure it seems.
Why not try the MeBr method Painkilla developped? It worked great for HQ to DMB, and you can recycled the bromide, whitout been exposed to any amount
of the methylating agent if you plan things ahead?
It could nice to see how Betaine goes, but I wouldn't recommend buying a kilo immediately.
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
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497
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| Quote: |
How would you react the two solids? As a solution/suspension in DMF or similar? |
As far as I can tell they are melted and reacted directly. I think the HQ melts and dissolves (some of?) the betaine, since betaine by itself melts
with decomp at ~305*C.
And thanks for telling me about the MeBr methylation, I hadn't seen that thread. I have often wondered whether it could be used, but never saw an
actual procedure until now.
Edit:
Yet another (maybe not so) quick question; is there a way to add -CH2-CHO to a phenol or methoxybenzene? Or is it possible to "formylate" a methyl
group?
The reason I ask is, if there was a half way simple way to 2,5-diMeO-phenylacetaldehyde it would be a piece of cake to get to the amine via
hydroxylamine to form the aldoxime and then Mg/NH4COOH/MeOH reduction...
It seems like there are a lot of possible routes, but I wonder if there are there any practical ones?
Theoretically you could go HQ -> HQdiacetate -> 2,5-diOH-acetophenone -> 2,5-diMeO-acetophenone -> 2,5-diMeO-phenylethanol ->
2,5-diMeO-phenylacetaldehyde... But that's way too many step to be practical, not to mention needing Ac2O..
Hmm... maybe like this? 2,5-diMeO-benzaldehyde -> 2,5-diMeO-mandelic acid -> 2,5-diMeO-acetylmandelic acid -> 2,5-diMeO-phenylacetaldehyde...
Not sure about the last step, but all the others seem to be quite high yielding according to this.
Or maybe.... 1,4-diMeO-benzene -> 2,5-diMeO-acetophenone via the Hosch reaction with acetonitrile...
Anyway it seems like an interesting possibility.. I really wouldn't mind avoiding the Pd/C, NaBH4, etc. involved with the alternatives.
PS. Another interesting reaction I just found: Acetonitrile reacts with benzyl alcohols with an HCl catalyst to form N substituted acetamides that can
then be easily acid hydrolyzed to amines. Not sure about yields though..
Acetonitrile with the benzyl chloride is another way, supposedly high yielding.
[Edited on 23-11-2008 by 497]
[Edited on 23-11-2008 by 497]
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Klute
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Well, you can halomethylate withe acetaldehyde and HX IIRC, then do a gabriel or go to the aldehyde (watch out phenylacetaldehdyes polymerise extremly
easily).
Your route via acetophenone will not work as you will obtain the 1-phenylethanol which cant be oxidized to pheneylacetaldehyde, just back
toacetophenone. You would need the primary alcohol b-phenethylalcohol.
You could alkylate diethylmalonate with a benzyl halide, hydrolyze and decarboxylate to the propanoic acid, form the amide and do a hoffman
degradation to the amide. I think there is a J Med Chem paper going on these lines.
The maandelic route doesn't seem very appealing to me, requiring cyanide and acetyl chloride, and having unknown yields.
The hösch reaction requires a very activated arene, and dimethoxybenzene is not activated enough. Maybe p-methoxyphenol could work there, but then
again there isn't any direct way from acetophenone that I recall off right now...
Unfortunaly, the benzyl alcohol and acetonitrile from a N-acetyl benzylamine. Your amine will be 1 carbon too short that your targeted compounds..
[Edited on 23-11-2008 by Klute]
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
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497
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| Quote: |
Well, you can halomethylate withe acetaldehyde and HX IIRC |
Great idea! I hadn't thought of that one. Just what I was looking for. Just quickly searching around, I haven't found much information on it though.
I'll have to look more.
Edit: Hah, I was searching "halomethylation" which obviously isn't going to happen with acetaldehyde  . It is 4:50 am here after all, I have an excuse at least..
| Quote: |
Your route via acetophenone will not work as you will obtain the 1-phenylethanol which cant be oxidized to pheneylacetaldehyde, just back
toacetophenone. You would need the primary alcohol b-phenethylalcohol. |
Oh well, I wouldn't really like that route even if it would work.
| Quote: |
The maandelic route doesn't seem very appealing to me, requiring cyanide and acetyl chloride, and having unknown yields. |
I agree...
| Quote: |
Unfortunaly, the benzyl alcohol and acetonitrile from a N-acetyl benzylamine. Your amine will be 1 carbon too short that your targeted compounds..
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 That's why I was hoping to use a phenylethanol (or chloride). I guess getting the
extra carbon on that side chain is really the biggest problem..
[Edited on 23-11-2008 by 497]
[Edited on 23-11-2008 by 497]
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stoichiometric_steve
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497, all you want is 2C-H?
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497
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| Quote: |
497, all you want is 2C-H? |
Why do you ask? I wouldn't want to do anything illegal!
But if I were , which I'm not, it seems like it would be awfully easy to go like so: HQ -> 4-MeO-phenol -> 1,4-diMeO-benzene ->
2,5-diMeO-phenylethyl chloride(bromide) -> 2,5-diMeO-phenethylamine...
I'm a little unsure of how well the haloethylation works. There seems to be quite a few patents and such that say it will, but I don't know how well,
especially with those methoxys on there. If the methoxys were a problem you could probably haloethylate HQ and methylate later... I think all the
other reactions are pretty much standard and well known, as long as the Delépine Reaction will in fact work on a -CH2-CH2-X.
As smuv says below, the Willgerodt-Kindler rearrangement could theoretically work, with sulfur, NH3, and pyridine it is said to get a pretty good
yield of 2-phenylacetamide from acetophenone, but what about a substituted acetophenone? And what does it take to reduce the acetamide to amine?
[Edited on 23-11-2008 by 497]
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smuv
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@ 497
Not that its very elegant, but phenylacetamides can be made from acetophenones through the Willgerodt-Kindler. The phenylacetamides can of course be
reduced to amines.
Additionally if you produce the propiophenone via the hoesch, nencki, or friedel-crafts you can produce the phenyl propionamide which theoretically
could yield the phenylethylamine after a hofmann rearangement.
Maybe not practical or elegant, but...hey it gets you there from xPhenones.
"Titanium tetrachloride…You sly temptress." --Walter Bishop
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Klute
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LiAlH4 or diborane reductions (NaBH4/BF3.Et2O, NaBH4/I2, etc) will reduce acetamides to amines.
Why is it you would like to avoid the traditional nitroalkene-nitroalkane-amine? Most of the reagents you mentionned above are much harder to aquire
than NaBH4 and Pd/C or even zinc dust.. If it's to explore new routes and compare results, god be with you 
Edit: IIRC the wildergot requires a pressure vessel, no? And forms H2S.. uck..
[Edited on 24-11-2008 by Klute]
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
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smuv
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| Quote: | | Edit: IIRC the Willgerodt requires a pressure vessel, no? And forms H2S.. uck.. |
There are variations of the reaction that don't require a pressure vessel, but I believe they are lower yielding. The wildgerodt does indeed produce
H2S (older variations also required H2S to help dissolve the sulfur).
Hey I never said it was good...I was just saying it could be done, and if
someone did it I would tip my hat to them (so long as the product was legal)
because the Willgerodt coupled with the Hofmann degradation is the most brutish method of making a phenylethylamine yet (IMO) from a mechanistic
standpoint uses two very beautiful reactions.
[Edited on 11-23-2008 by smuv]
"Titanium tetrachloride…You sly temptress." --Walter Bishop
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497
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| Quote: |
LiAlH4 or diborane reductions (NaBH4/BF3.Et2O, NaBH4/I2, etc) will reduce acetamides to amines. |
Shit... that's exactly what I'm trying to avoid...
| Quote: |
Why is it you would like to avoid the traditional nitroalkene-nitroalkane-amine? Most of the reagents you mentionned above are much harder to aquire
than NaBH4 and Pd/C or even zinc dust.. If it's to explore new routes and compare results, god be with you |
Well, I guess I have some glimmer of hope that there is an easier way hiding out there somewhere... Maybe that's being a little too optimistic  . Also I want to avoid NaBH4/LiAlH4 if at all possible.
Now that I think about it, part of the reason is simply that I really enjoy trying to solve problems and/or find better ways to do things. And if
something I come up with happens to help someone else down the line, all the better.
| Quote: |
because the Willgerodt coupled with the Hofmann degradation is the most brutish method of making a phenylethylamine yet (IMO) from a mechanistic
standpoint uses two very beautiful reactions. |
Hah, well said.
Still for some reason I really like the idea of making an aldoxime and then reducing it. Both of those reactions are pretty high yielding and require
only very basic reagents and conditions. Like really basic, KNO2, HCl, NaHSO3, H2SO4, NaOH, methanol , toluene, NH4COOH and Mg... Just
getting the damn 2-phenylacetaldehyde... that's what holds everything up.
I did see a patent where they do a one-pot synth of benzaldoximes directly from brenzal bromides with a >95% yield... But I can't think of any way
of getting the bromide that would work with a MeO substituted benzene... it is easy to get the benzal bromide via H2O2/HBr/H2O/CHCl3 reacting with
toluenes(or ethylbenzenes in my case), but it apparently only works with deactivated toluenes like p-nitrotoluene, so I guess that won't work..
Anyway... Going back to the traditional route, is there a good way to go from nitrostyrene to amine directly. I've seen were they did it with Zn, etc
but I never saw a decent yield..
[Edited on 23-11-2008 by 497]
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Maja
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Maybe some ideas how to separate toluene and N-butanol ?
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JohnWW
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| Quote: | Originally posted by Maja
Maybe some ideas how to separate toluene and N-butanol ? |
Some sort of gas-liquid chromatography may be
possible, on an appropriate medium in the packed column (a substance which strongly adsorbs one but not the other). Their boiling-points, 110.8 and
117ºC respectively, are too close for a simple distillation to be effective; and in any case, according to Perry chapter 13, n-butanol and toluene
form a minimum-boiling-point azeotropic mixture with a boiling-point of 105.5ºC containing 37% n-butanol. So, noting that n-butanol is soluble in
water to the extent of 9 parts in 100 parts of water at 15ºC while toluene is practically insoluble (only 0.05 parts in 100 parts of water at the
same temperature), the most effective type of non-chemical separation would be by solvent extraction with water, which could be multi-stage to be
fully effective.
Failing that, a chemical separation would be necessary, most likely involving a reaction that n-butanol (which is more reactive) undergoes as a
primary alcohol (e.g. esterification with an acid, other than nitric acid or another acid that would nitrate or sulfonate the toluene, or formation
of a butoxide by reaction with an alkali metal), but which toluene as an aromatic hydrocarbon does not undergo. The resulting esters would be soluble
in several polar solvents in which toluene is insoluble, and they would also have much higher boiling-points than toluene. The alkali metal butoxides
would be insoluble in toluene, but soluble, without reacting, in non-protonating polar solvents in which toluene would be much less soluble; or they
could be hydrolysed, after evaporating or distilling off the toluene, back to n-butanol and an alkali metal hydroxide by adding water.
[Edited on 27-11-08 by JohnWW]
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Maja
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Thank you ! Extracting sounds good, but I would like to keep butanol it would be handy ! I will try simple esterification with acetic acid with a few
drops of H2SO4...
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Klute
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497, well you can get benzyl bromide via bromomethylation, which requires very accesable reagents and apparently proceeds well (even very well in some
case).
What is the procedure benzyl bromide --> benzaldoxime? Do you have a ref?
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
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raiden
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I have a quick question! How the hell do you work a vacuum pump? I've one that has been sitting around for months and would like to actually give it a
whirl. Do you just connect it and turn it on or what? How do you release the vacuum? How do you stop it from going too far and crushing the g/ware?
Cheers.
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solo
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Just put an in line valve and turn it up as needed and shut it off when you want....solo
It's better to die on your feet, than live on your knees....Emiliano Zapata.
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Nicodem
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| Quote: | Originally posted by raiden
I have a quick question! How the hell do you work a vacuum pump? I've one that has been sitting around for months and would like to actually give it a
whirl. Do you just connect it and turn it on or what? How do you release the vacuum? How do you stop it from going too far and crushing the g/ware?
Cheers. |
Essentially you use the on/off switch and that's it (after you check if there is enough oil, of course). Also, unless you want to ruin it with
corroding chemical vapours you also need to attach a liquid nitrogen trap in the vacuum line. I do not understand your question about "crushing the
g/ware". Just about any round bottom flask is supposed to be rated for 1 bar, so I do not know what kind of glassware you want to use which is not
resistant to 1 bar pressure difference. Give more details about it.
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raiden
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| Quote: | Originally posted by Nicodem
Essentially you use the on/off switch and that's it (after you check if there is enough oil, of course). Also, unless you want to ruin it with
corroding chemical vapours you also need to attach a liquid nitrogen trap in the vacuum line. I do not understand your question about "crushing the
g/ware". Just about any round bottom flask is supposed to be rated for 1 bar, so I do not know what kind of glassware you want to use which is not
resistant to 1 bar pressure difference. Give more details about it. |
How does one check the oil! I best find the model number and a manual I think!
Ahh, sorry, I just thought that most glassware would only be able to take a certain amount of vacuum and if you left the pump on it would implode
them.
Thanks for clearing this up!
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