Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: GCT on April 30, 2005, 09:29:15 PM
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This problem is somewhat related to a recent question we had in the organic chemistry forum.
Does anyone here know how one would synthesize 3-phenylpropanal from bromobenzene in three steps?
How about 3-phenylpropanol?
I vaguely recall a clever method used to accomplish this task, although this can certainly be my imagination.
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Here is the link to the thread in the organic forum. In that question, I think the starting material was benzyl bromide, not bromobenzene.
http://www.chemicalforums.com/index.php?board=3;action=display;threadid=3006
Starting from bromobenzene would also be possible in three steps for either the alcohol or the aldehyde.
GCT, if you want I can IM you my idea, I don't want to post it since I think it's a good problem for the non-staff people to ponder.
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I've never "IM" before, although I'm thinking about starting soon. For now, can you send the proposal through private messaging? Thanks.
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Heh, that's actually what I meant by IM.
I'll send it now.
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i am hardly familiar with organic chemistry nowadays, but i think it involves replacing bromo with a C=C group.
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can someone write the structure oF 3-phenylpropanal ?
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@-CH2-CH2-CH=O
where @ represents the benzene ring
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Br-benzene +Mg+ Br-allyl
BH3/HOOH/OH
Swern O
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wow. this thread is jumpin!!!!
a week, and still not one post?? :(
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Alright!!!Next question of the day ??? ???
go from 3-methoxybenzaldehyde to 3-hydroxyphenylacetaldehyde in TWO steps!!!!
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Heh, that one is a lot tougher than the original question.
Doable, but a lot more difficult!
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Incidentally, how do you turn an ether into an alcohol?
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Incidentally, how do you turn an ether into an alcohol?
It's usually quite difficult, but in the case of aryl-alkyl ethers it's much easier. There are several common reagents for this process, the key to this problem is knowing which precise one you need to save yourself a step!
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for aryl ethers, simple koh followed by methyl iodide (or eq)...or dimtheyl sulfate (or equiv) could be used.
for alkyl ethers, use williamson ether synth.
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:D Alright!!
It's time for the answer to the first question of the day (since we didn't get any guesses?)
1. we first need to do a wittig reaction with the aldehyde. adding the Levine Wittig reagent (triphenylphosphoniummethoxymethyl bromide)...
we have thus formed our new double bond... :)
but this, my friends, is no ordinary double bond...
What we have is a vinyl ether ;D
2. If we hydrolyze the vinyl ether with something strong enough to simultaneously deprotect the aryl ether, we have our product!!! (remember, vinyl ethers are really just aldehydes or ketons in disguise!!) A reagent that will affect this elegant transformation would be HBr/acetic acid.
Time for a new question...COME ON...easy or difficult, someone post a question
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for aryl ethers, simple koh followed by methyl iodide (or eq)...or dimtheyl sulfate (or equiv) could be used.
for alkyl ethers, use williamson ether synth.
This would be to make the ether, not cleave it, yes?
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Okay, tough one:
Benzyl alcohol to methyl benzoate in one step.
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Br-benzene +Mg+ Br-allyl
BH3/HOOH/OH
Swern O
woa back up a minute here, why don't you show us a diagram (using chemical software). I'm guessing that you would want the grinard complex to attack the terminal halogenated carbon right? It would probably work, being a terminal allyl carbon. However, have we considered whether the double bond would be a problem?
could Br-benzene+Mg+Br-allyl be completed within one experimental step?
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Okay, tough one:
Benzyl alcohol to methyl benzoate in one step.
I've seen this in Designing Organic Synthesis, unfortunately I don't have the book with me. It's quite simple really, from what I remember, some sort of modified oxidation, with a little twist from the standard.
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To GCT ;)
1. sorry, havent downloaded chemdraw on this computer
2. gringards readily participate in SN2 reactions such as the one I mentioned...gringard is the nucleophile, allyl bromide is the electrophile. this rxn would have to be done in THF, as SN2 substitutions are best carried out in polar aprotic solvents.
2. gringards do not react with double bonds.. that's just a fact of organic chemistry :)...double bonds can react with a number of lewis acids, but not lewis bases!!!
3. now, why dont you propose a new question for us ???
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GCT--
this may work in -'one pot'...
KmnO4/ OH will give the carboxylate salt...,
adding diazo methane in situ would give methyl benzoate (as diazo methane and carboxylates are known to give esters, and release N2.
I am sure that there are more elegant ways to affect this transformation :'(
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2. gringards do not react with double bonds.. that's just a fact of organic chemistry :)...double bonds can react with a number of lewis acids, but not lewis bases!!!
Well, this is sort of a special case because there is the possibility of an SN2' attack on allyl bromide as well. That would involve the Grignard reagent reacting with the allyl group. Hard to tell the difference between the two mechanisms though because the product is the same. You might be able to differentiate the two attacks with a deutero labelled allyl bromide.
Also, the magnesium ion is a pretty good Lewis acid, so don't discount Grignard reagents as solely Lewis bases.
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GCT--
this may work in -'one pot'...
KmnO4/ OH will give the carboxylate salt...,
adding diazo methane in situ would give methyl benzoate (as diazo methane and carboxylates are known to give esters, and release N2.
I am sure that there are more elegant ways to affect this transformation :'(
hmm....pretty neat, I'll have to look into this a bit more. Movies, is this what you had in mind? Let's resolve this brainteaser before moving on.
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come on, movies...do tell...
benzyl alcohol to methyl benzoate ???
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come on, movies...do tell...
benzyl alcohol to methyl benzoate ???
He's actually gone for the moment, will be back monday or perhaps tuesday at the latest. Guess we'll need to wait till then
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Sorry, was out of town for the weekend. The reaction I was thinking of is a modified procedure for benzyllic oxidation with MnO2. If you run the reaction in methanol solvent with added sodium cyanide, then the methyl ester is formed in one reaction process. A neat trick, I think.
Corey first reported this (J. Am. Chem. Soc. 1968, 90, 5616-5617).
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Very neat, indeed. We should expect nothing less from Corey: (He's still going strong at Harvard as we speak.)
Can we work through the mechanism:: ;)
1. benzyl alcohol to benzaldehyde
2. addition of cyanide to the carbonyl (aldol rxn)
3. anionic oxygen the previously was carbonyl oxygen takes a proton from methanol
4. methoxide attacks the cyano group of the aldol adduct
5. the now negatively charges N of the previous cyano group takes the proton from the OH at the benzyl position...
6. Any suggestions for the rest of the mechanism/ and or corrections for the fisrt part??
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Well, first of the cyanide addition isn't an aldol process, it's a Strecker type addition, but regardless it's okay up to that point. The key is the once the cyanide adds into the aldehyde you have what amounts to a benzyl alcohol derivative, which is again oxidized by MnO2. The product is an acyl cyanide, which is quite reactive (see Mander's Reagent). It turns out that CN- is a better leaving group than MeO-, so methanol exchanges in a process similar to trans-esterification.
The mechanism for oxidation by MnO2 in itself is pretty interesting. Anyone care to take a stab at it?
Mander's reagent reference: Tetrahedron Lett. 1983, 24, 5425-5428.
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I like IT!!
sorry about the aldol reference.
i didnt take into acct that MnO2 would be coming into play a second time.
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I like IT!!
sorry about the aldol reference.
i didnt take into acct that MnO2 would be coming into play a second time.
Heh. It's a tricky one indeed. MnO2 is such a poor oxidant that you usually have to use around 5 equivalents of it, even for a regular alcohol oxidation (to a ketone or aldehyde).
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wow.. organic chemists.. im impressed although im just a lowly engineer..
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SOS Please !!!!!
How can I down load this article?
Mander's reagent reference: Tetrahedron Lett. 1983, 24, 5425-5428.
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You need to have a subscription to the Tetrahedron Letters archives. If you are at a university, they may have online access. If not, you could check at a physical sciences library. This is a very popular journal, so most physical sciences libraries would have it.
Here is a link to the website of the journal:
http://www.sciencedirect.com/science/journal/00404039
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I am thinking about this route:
Ph-Br + Mg --> Ph-MgBr
Ph-MgBr + Br-CH2CH2CH(OC2H5)2-->PhCH2CH2CH(OC2H5)2 + MgBr2
-->acid hydrolize-->product
I am not sure if 3-brompropanal is commercially available.
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Yeah, that route ought to work too. 3-Bromopropanal wouldn't be a fun compound to work with because it would rapidly eliminate to form acrolein and acrolein is a pain to deal with too because it polymerizes!
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Aha movies you right abot 3-brompropanal stability. Also i have some doubts about the Grignard reaction with the ethylacetal of it. What do you think about lability of H from the protected acetal(CH(OR)2) ???
I have some believe its not enogh labile to react with Grignard like PhMgBr. Heres the known Bodroux-Chichibabin method for reaction Grignard with orthoformiat:
R-MgX + CH(Oc2H5)3--> R-CH(OC2H5)2 + Et-OMgX
By this method it sems reaction stop to the acetal but i dont know. May be Zerevitinov not working here ;)
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Acetals are usually stable towards Grignard reagents. There are loads of examples of this.
The orthoformate example is a whole different ballgame. Orthoesters tend to be a bit more reaction than corresponding acetals. Note that in your example the product is an acetal, which if it can be isolated from that reaction, must be stable towards the Grignard reagent!
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Yes indeed movies!
Acetal group good protecting in grignard reaction and in many other too. I am wondering if possible some synthesis of 3-chlorpropanal from epichlorhidrine. Cl-CH2-CH-epovy-CH2 or from the corresponding 3chlor-1,2 propandiol ???
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Why not just start with 3-Bromopropanol, protect the alcohol as a silyl ether, then add the Grignard, cleave the silyl ether, and oxidize the primary alcohol? More steps, but pretty straight forward chemistry.
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Good idea! Theres so many methods for selective oxidation primary alcohols to aldehydes which do you think best for this preparation?
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If you do it at the end there isn't really anything else that is particularly sensitive to oxidation, so something like pyridinium dichromate ought to do it. There are tons of other ways, but chromium is cheap and pretty easy to use. Other alternatives are TPAP/NMO, Dess-Martin Periodinane, PCC, Swern oxidation (or any of the other activated DMSO oxidations).
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Dess-Martin Periodinane method is cool but may be some cheap.Before some time i red an article for very efficient and selective oxidation primary alcohols to cor aldehydes with the system Acetic anhydride/NaNO2. The yelds described are cool also the reagents if it really works ;) But do someone can explain me the mechanism of action and reaction these two reagents and the alcohol ??? The only reaction i can think first is NaNO2+Ac2O-> CH3COONa + CH3CONO2 but may be this compound very unstable and give some reactive intermediates like nitronium or something like?