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Offline Fireredburn1

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transformation of furan propose mechanism
« on: May 11, 2015, 02:07:28 AM »
Hi for this question I need to propose a mechanism for a two step transformation of furan into some hydroxy-pyrrole compound.




The first step involves Br2, MeOH, which I have already figured out . My problem comes at the second step. Given that the first step and its product is correct (which i hope is), how do I use NH2OH to get my final product?

First product is as shown below



Im guessing the intermediate formed for the second step is this? I'm but not sure how it gets to the final product anyway. The number of hyrogen atoms do not match. If i eliminate im supposed to lose 2 hydrogen atoms, but for the intermediate and final product there are the same no. of hydrogen atoms (4 in fact) .


Offline pgk

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Re: transformation of furan propose mechanism
« Reply #1 on: May 11, 2015, 01:31:11 PM »
What about ring opening, followed by reaction with hydroxylamine and ring closure?
But, firstly:
1). How does Br2 in methanol solution, react with a double bond?
2). And how does Br2 in methanol solution, react with conjugated double bonds?

Offline orgopete

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Re: transformation of furan propose mechanism
« Reply #2 on: May 12, 2015, 09:04:13 PM »
I agree with the premise. I think this requires two equivalents of hydroxylamine (no mechanism).
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Offline pgk

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Re: transformation of furan propose mechanism
« Reply #3 on: May 13, 2015, 01:34:43 PM »
One molecule of hydroxylamine is enough. But please, remember that hydroxylamine cannot easily substitute a vinyl bromide via SN2 mechanism.

Offline Dan

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Re: transformation of furan propose mechanism
« Reply #4 on: May 14, 2015, 04:43:41 AM »
One molecule of hydroxylamine is enough. But please, remember that hydroxylamine cannot easily substitute a vinyl bromide via SN2 mechanism.

I think a second equiv of hydroxylamine is required, the second step needs a reducing agent.

I would not predict the formation of a vinyl bromide, what are you getting at with that point?
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Offline pgk

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Re: transformation of furan propose mechanism
« Reply #5 on: May 14, 2015, 12:34:53 PM »
Sorry. This is a bad expression.
The right is “hydroxylamine cannot substitute a vinyl bromide via SN2 mechanism but could easily substitute an allylic one”.
Sorry, again.

Offline orgopete

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Re: transformation of furan propose mechanism
« Reply #6 on: May 14, 2015, 03:19:03 PM »
Two things, we haven't heard from the original poster and, if my memory serves me correctly, the op has given the actual product of the reaction of furan with bromine in methanol. I can anticipate that an electrophilic addition of bromine would give an oxygen stabilized allylic cation that methanol attacks. Solvolysis of the bromide will give the intermediate shown.
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Offline orgopete

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Re: transformation of furan propose mechanism
« Reply #7 on: May 15, 2015, 02:52:58 AM »
Re: formation of dihydrofuran from furan

But, let’s start from the beginning. Oxygen activates the bromine addition, by forming an oxonium anion and stabilizes the system by forming a conjugated double bond. Which is then attacked by methanol. Then, another oxonium formation, another conjugated stabilization and a bromide anion, in acidic medium (HBr is generated, during reaction) like colour change of delphinidine and pellargonidine pigments, in acidic medium. Until here, it sounds well. But suddenly, the hard oxonium conjugated system is destroyed by the soft methanol base, in strong acidic conditions (HBr continues to generate, during reaction). The latter doesn’t sound well, at all. The only reasonable mechanistic pathway can be based on using catalytic amounts of bromine.
Anyway, assuming that this reaction occurs herby, leading to the proposed intermediate. This is not the essential, but rather: how a Paal–Knorr like reaction mechanism can occur in dehydro- (hydrogen deficient) system. Please, remeber that there is a double bond in the 3,4 – position of the furan ring.

Oxonium anion, huh? This is an OrgSyn Prep (http://www.orgsyn.org/demo.aspx?prep=CV5P0403).
Someone posted what appears to be a perfectly reasonable mechanism so I needn't repeat it, http://www.orgmech.co.uk/mech.php?&Num=75.
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Offline pgk

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Re: transformation of furan propose mechanism
« Reply #8 on: May 15, 2015, 06:34:37 AM »
Sorry orgopettte and everybody, for the misspelling. This is a serious mistake.
The right is OXONIUM CATION.

Offline pgk

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Re: transformation of furan propose mechanism
« Reply #9 on: May 15, 2015, 11:20:04 AM »
“But suddenly, the hard oxonium conjugated system is destroyed by the soft methanol base, in strong acidic conditions (HBr continues to generate, during reaction). The latter doesn’t sound well, at all.”
However, if you read carefully the operational protocol of the preparation of 2,5-dihydro-2,5-dimethoxyfuran that is described in the cited reference (notably: Organic Syntheses, 40, 29, (1960)), you will observe that the reaction does not occur under strong acidic conditions, due to the addition of a large excess of Na2CO3. Besides, I am not sure if the preparation of N-hydroxy-pyrrole could occur under alkaline conditions that furan ring opening, followed by pyrrole ring closure is very slow. Is it an one-pot reaction or not?

« Last Edit: May 15, 2015, 11:57:08 AM by pgk »

Offline pgk

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Re: transformation of furan propose mechanism
« Reply #10 on: May 15, 2015, 01:45:50 PM »
Please, take a look to the attached mechanism scheme, hereby and discuss about, in publicity.The proposed mechanistic model keeps the correct oxidation level.
The reaction occurs via a nitrone (imine nitroxide, imine N-oxide) intermediate.
Nitrones of conjugated aldehydes and ketones, are formed rather easily by a simple condensation with the corresponding oxime, in ethanol.
1). Collection of Czechoslovak Chemical Communications, 16, 258-267, (1951)
http://cccc.uochb.cas.cz/16/0/0268/
2). Chemical Reviews, 64(4), 473–495, (1964), p.479
http://pubs.acs.org/doi/abs/10.1021/cr60230a0
It seems that the anti- N-isomerism of the corresponding oxime is critical for the formation of nitrones.
Journal of the Organic Chemistry, 32(2), 261–265, (1967)
       
http://pubs.acs.org/doi/abs/10.1021/jo01288a002

« Last Edit: May 15, 2015, 02:22:37 PM by pgk »

Offline orgopete

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Re: transformation of furan propose mechanism
« Reply #11 on: May 15, 2015, 02:21:07 PM »
“But suddenly, the hard oxonium conjugated system is destroyed by the soft methanol base, in strong acidic conditions (HBr continues to generate, during reaction). The latter doesn’t sound well, at all.”
However, if you read carefully the operational protocol of the preparation of 2,5-dihydro-2,5-dimethoxyfuran that is described in the cited reference (notably: Organic Syntheses, 40, 29, (1960)), you will observe that the reaction does not occur under strong acidic conditions, due to the addition of a large excess of Na2CO3. Besides, I am not sure if the preparation of N-hydroxy-pyrrole could occur under alkaline conditions that furan ring opening, followed by pyrrole ring closure is very slow. Is it an one-pot reaction or not?

I think you are going way further than needed. I am presuming this is a typical kind of question posed to a student. The mechanism that I found seems simple enough for the assignment.

Re: acidity
t-Butyl bromide can be solvolyzed in a polar solvent without additional base being present. If the medium does become sufficiently acidic or if HBr were added, the reaction can be reversed. The problem specified did not mention how it was to be carried out, but rather the minimum information. Granted it had been a long time since I had seen the formation of a dihydrofuran, the intermediate indicated by the original poster seemed right and could reflect a reference found. Furthermore, I would be surprised if the reaction were to stop at the bromide in the absence of carbonate.

One can estimate the ease of solvolysis from the reverse reaction. For example, acetobromoglucose is also an Org Syn prep, http://www.orgsyn.org/content/pdfs/procedures/cv3p0011.pdf.
You may examine the conditions and estimate the equilibrium from a mixture of HBr and methanol. Although I grant some bromide may exist, the conditions suggest solvolysis may be a quite easy reaction, especially as the bromide is used to prepare sugar derivatives.

Re: reaction with hydroxylamine
reaction were to stop at the bromide in the absence of carbonate.

One can estimate the ease of solvolysis from the reverse reaction. For example, acetobromoglucose is also an Org Syn prep, http://www.orgsyn.org/content/pdfs/procedures/cv3p0011.pdf.
You may examine the conditions and estimate the equilibrium from a mixture of HBr and methanol. Although I grant some bromide may exist, the conditions suggest solvolysis may be a quite easy reaction, especially as the bromide is used to prepare sugar derivatives.

Re: reaction with hydroxylamine
Again, we should consider how the problem is written. I have used both hydroxylamine and its hydrochloride. Without searching, I don't think the free amine is commercially available, hence any indication of its use probably refers to the HCl salt. Clearly, the problem shows the reaction is a second reaction. Since the starting material is a dihydrofuran, the aromatic product does not follow from the indicated reaction. This would seem to be exactly what the poster was asking about. A solution to this dilemma is that a second equivalent of hydroxylamine is needed and it must operate as an oxidant.

Since the intermediate is an acetal, logically an acid may be required to open it for a reaction with hydroxylamine. Whether the hydrochloride present or residual HBr may be present, I don't know. None the less, I think the purpose of the poster was to attempt to write a mechanism, even if this may have required real or imaginary reagents.  We sometimes have realize problems have been written with errors. Although this creates a problem for students, it can be helpful if someone with enough expertise can recognize this possibility. This is still just a mechanism question.
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Offline orgopete

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Re: transformation of furan propose mechanism
« Reply #12 on: May 15, 2015, 02:31:31 PM »
Please, take a look to the attached mechanism scheme... The proposed mechanistic model keeps the correct oxidation level.
The reaction occurs via a nitrone (imine nitroxide, imine N-oxide) intermediate.
Nitrones of conjugated aldehydes and ketones, are formed rather easily by a simple condensation with the corresponding oxime.
1). Collection of Czechoslovak Chemical Communications, 16, 258-267, (1951)
http://cccc.uochb.cas.cz/16/0/0268/
2). Chemical Reviews, 64(4), 473–495, (1964), p.479
http://pubs.acs.org/doi/abs/10.1021/cr60230a0
It seems that the anti- N-isomerism of the corresponding oxime is critical for the formation of nitrones.
Journal of the Organic Chemistry, 32(2), 261–265, (1967)
       
http://pubs.acs.org/doi/abs/10.1021/jo01288a002
I don't have access to any of these articles.

If someone has shown that a bis-oxime can condense to give the cyclic hydroxylamine, that's fine. This still is requiring two equivalents and an unspecified(?) reaction to get the product. I say unspecified only that I don't think the poster would have encountered it, not that one cannot be written. (Perhaps one is shown in the citations.)

I think I'm done here.
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Offline Dan

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Re: transformation of furan propose mechanism
« Reply #13 on: May 16, 2015, 03:47:23 AM »
Please, take a look to the attached mechanism scheme, hereby and discuss about, in publicity.The proposed mechanistic model keeps the correct oxidation level.

No, your mechanism contains a fundamental arrow pushing error - see below.
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Offline pgk

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Re: transformation of furan propose mechanism
« Reply #14 on: May 16, 2015, 02:06:46 PM »
Thank's, Dan.

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