Sciencemadness Discussion Board

Condensation

shrent - 18-6-2006 at 04:25

I'm trying condensation reaction between two esters, i.e. alanine-t-butyl/benzyl ester & an alpha-bromoester as under :


PhCH2CH2CH(Br)COOC2H5 + CH3CH(NH2)COOR

to

PhCH2CH2(COOC2H5)CHNHCH(CH3)COOR


where, R=Benzyl/t-butyl.

i.e. eliminating HBr in this reaction.

I have just one reference route for this using acetonitrile as solvent & adding TEA & both of the reactants, all in eq.molar prop. & reflux for over 2 days.....But still not getting good conversion.....

Can I get any other route for this condensation ?

Sandmeyer - 18-6-2006 at 05:52

This is not a condensation, and there are many references to be found using beilstein, yields for the substitution are good to excellent. Do your own litterature searches...

[Edited on 18-6-2006 by Sandmeyer]

Type of reaction

shrent - 22-6-2006 at 04:26

Dear Sandmeyer,

Pls forgive my ignorance, but can you just inform me, if it is not the condensation then what the exact type of this reaction is. :(

I mean under which category, keywords, I should search for literature for this reaction ?


;)

Sandmeyer - 22-6-2006 at 10:24

As allready mentioned -- it's a substitution. Searching the litterature by keyword in this case isn't the best option, but if you don't have beilstein orgsyn is a wonderful non-profit resource, for instance there is a compilation of substitution reactions: http://www.orgsyn.org/orgsyn/RxnTypes/section.asp?section=24... amine substituting a halogen: http://www.orgsyn.org/orgsyn/RxnTypes/section.asp?section=25... see in particular amino acids and derivatives..



[Edited on 22-6-2006 by Sandmeyer]

unionised - 23-6-2006 at 00:04

It B****y well is a condensation reaction.
http://en.wikipedia.org/wiki/Condensation_reaction

Sandmeyer - 23-6-2006 at 01:36

Quote:
Originally posted by unionised
It B****y well is a condensation reaction.
http://en.wikipedia.org/wiki/Condensation_reaction


Don't know what the hell you mean by 'B****y' but I propose the following mechanism:



[Edited on 23-6-2006 by Sandmeyer]

enhzflep - 23-6-2006 at 18:48

B****y --> Bloody ?

unionised - 24-6-2006 at 00:55

"B****y --> Bloody ? "
Yep.

I agree that's probably the mechanism (Some Sn1 contribution wouldn't shock me greatly).
Since ther's a base catalyst I think it probably fulfills the role that you have ascribed to Br- attacking the +ve charged intermediate and pinching the proton.

The point is that it remains a condensation.
On a practical note the one thing I would make sure of is that all the materials were dry. water and a base catalyst would destroy the reactants and the product. You might also get transesterification if you are unlucky.

Nicodem - 24-6-2006 at 02:31

Oh please! Read the definition of condensation from the first paragraf od the link you yourself provided. It is not a condensation. It is a simple monoalkylation of an amine. Alpha-bromo esters are electrophiles just like alkil bromides, only considerably more reactive. Water does no harm to this reaction if only a mild base is used and not too high temperatures (and the esters won't hydrolyze).

[Edited on 24-6-2006 by Nicodem]

unionised - 24-6-2006 at 04:11

OK, here's the definition.
"A condensation reaction (also known as a dehydration reaction or dehydration synthesis when water is lost) is a chemical reaction in which two molecules or moieties react and become covalently bonded to one another by the concurrent loss of a small molecule, often water, methanol, or a type of hydrogen halide such as HCl."

I don't see how this doesn't apply.

Since the molecule lost in this case is not water it's not a dehydration so the bit in brackets doesn't apply.
It's "a chemical reaction". Any debate about this?

"two molecules react." Specifically these "PhCH2CH2CH(Br)COOC2H5 + CH3CH(NH2)COOR"

"and become covalently bonded" The new bond is between the nitrogen and a carbon.
"With the concurrent loss of a small molecule" In this case it's HBr.

The concurrency might be moot but I'd be quite happy to redraw the reaction with the base catalyst providing the electrons to the proton as a concerted step with loss of the hydrobromide salt.

Just out of curiosity, what do you think is a classic condensation reaction?

"Oh please! Read the definition of condensation from the first paragraf od the link you yourself provided. It is not a condensation. It is a simple monoalkylation of an amine. Alpha-bromo esters are electrophiles just like alkil bromides, only considerably more reactive. Water does no harm to this reaction if only a mild base is used and not too high temperatures (and the esters won't hydrolyze).
"
Triethylamine is quite a strong base.
The reaction is being boiled for 2 days in acetonitrile - about 80C.
As you point out, the bromoester is more susceptible to hydrolysis than an alkyl bromide would be.

[Edited on 24-6-2006 by unionised]

Sandmeyer - 24-6-2006 at 04:35

Quote:
Originally posted by unionised
OK, here's the definition.
"A condensation reaction (also known as a dehydration reaction or dehydration synthesis when water is lost) is a chemical reaction in which two molecules or moieties react and become covalently bonded to one another by the concurrent loss of a small molecule, often water, methanol, or a type of hydrogen halide such as HCl."

I don't see how this doesn't apply.
.
Since the molecule lost in this case is not water it's not a dehydration so the bit in brackets doesn't apply.
It's "a chemical reaction". Any debate about this?


No it's just a case of you desperately want to be right even though you are wrong.
Quote:
Triethylamine is quite a strong base.
The reaction is being boiled for 2 days in acetonitrile - about 80C.
As you point out, the bromoester is more susceptible to hydrolysis than an alkyl bromide would be.


Ethoxide, if it's to be formed, would be the strongest nucleophile/base in the anhydrous reaction system so I can't see how this ester is supposed to hydrolyse. Triethylamine is a base but it really is a lowsy nucleophile, its role here is to act as a proton-scavenger so that the aminoester dosen't get protonated and thereby become rendered non-nucleophilic. There are many references on this type of reaction -- time ranging from couple of hours to days, that's why TLC is so handy. I'd guess the reason for '2 days' in this particular one is that the workers let the reaction run over weekend, the yield of the wanted product was excellent, there was no "hydrolysis".


[Edited on 24-6-2006 by Sandmeyer]

[Edited on 24-6-2006 by Sandmeyer]

Original reference

shrent - 24-6-2006 at 05:13

Dear friends !

Herewith I had attached the original file in which the "condensation" ("according to the inventors") has been done as I informed earlier.

Pls take a look at that & then comment about your views.....:)

Attachment: OPPI_1983.pdf (215kB)
This file has been downloaded 661 times

Sandmeyer - 24-6-2006 at 05:28

Quote:
Originally posted by shrent

Herewith I had attached the original file in which the "condensation" ("according to the inventors") has been done as I informed earlier.


Then the inventors need to dust off their elementary organic chemistry books...

Nicodem - 24-6-2006 at 05:55

The difference from a condensation is that during the formation of a covalent bond in an alkylation of an amine no “concurrent loss of a small molecule” happens. You get the amine salt so no other molecule forms on the right side of the equation. If you are referring to the apparent loss of “HBr” than you should check the equation again as it is only a formal way of writing down the neutralization step (which is a separate reaction step anyway).
I never heard anybody refer to alkylations of amines as condensations before except maybe in a figurative way without sticking to the definition like the authors of the paper Shrent attached (peer reviewing truly sucks :().

PS: It’s not that I really care how anybody calls this reaction, I just found Unioniseds’ “B****y” assuredness annoying enough to post a “B****y” reply. :)

frogfot - 25-6-2006 at 01:34

Just wondering, is there any risk of intermolecularly catalysed transesterification? I mean the final product has two ester groups positioned very close. The carbonyl group of one ester group can "activate" the second ester group. This will give a 6 memered ring transition state, maybe more active towards transestirification?

unionised - 26-6-2006 at 10:03

I can't find the data for triethylamine in acetonitrile but for the trimethylamine the pkb is about 17.6. That makes it at least comparable with ethoxide, quite possibly stronger.

In the Claisen condensation, the deprotonated enolised ester atacks the carbonyl group of a second ester. At this point there has been a new CC bond generated but no loss of any small molecule.
OMG, because the steps are not concerted the Claisen condensation isn't a condensation.
The loss then takes place; the loss of alkoxide, that's to say an ion rather than a molecule.
Holy Hell! it really isn't one.

Of course, the aldol condensation never was a real condensation.

Another possibillity is that the word "condensation" is widely and loosely used in chemistry. If that were the case then starting out a post by saying "it isn't a condensation" would be inaccurate and a bit bloody self assured. Just the sort of thing that I might reply to.

About the hydrolysis.
This is what I actually wrote
"On a practical note the one thing I would make sure of is that all the materials were dry. water and a base catalyst would destroy the reactants and the product. You might also get transesterification if you are unlucky. "

OK, quite clearly I'm saying IF it isn't anhydrous then you might get hydrolysis.

Any point you chose to make about anhydrous conditions can be as interesting and (even) accurate as it likes. It's still not relevant. Why did you chose to bring it up?

Of course, all this is very interesting stuff but I'm sure everyone has now formed their own opinions on whether the original reaction is a condensation.

Can anyone help answer the original question, why is the yeild poor?

[Edited on 26-6-2006 by unionised]

Sandmeyer - 26-6-2006 at 12:45

Quote:
can't find the data for triethylamine in acetonitrile but for the trimethylamine the pkb is about 17.6. That makes it at least comparable with ethoxide, quite possibly stronger.


I don't get the connection to topic of this thread, please explain in terms of reactants and products.
Quote:
In the Claisen condensation, the deprotonated enolised ester atacks the carbonyl group of a second ester. At this point there has been a new CC bond generated but no loss of any small molecule.
OMG, because the steps are not concerted the Claisen condensation isn't a condensation.
The loss then takes place; the loss of alkoxide, that's to say an ion rather than a molecule.
Holy Hell! it really isn't one.


No, there is a net loss of ethanol not ethoxide -- being a strong base once ethoxide is formed it instantly deprotonates the carbon between 2 carbonyl groups -- equilibrium favours the formation of ethanol and a resonance stabilised enolate, it stops there. Only upon the acidic workup do you get the beta-ketoester.
Quote:
Of course, the aldol condensation never was a real condensation.


Are you sure :)
Quote:
If that were the case then starting out a post by saying "it isn't a condensation" would be inaccurate and a bit bloody self assured. Just the sort of thing that I might reply to.


Sorry for posting that horrible sentence - but I'm an asshole and can't help it.
Quote:

Any point you chose to make about anhydrous conditions can be as interesting and (even) accurate as it likes. It's still not relevant. Why did you chose to bring it up?


I brought it up simply since it's true, is that a problem?
Quote:
Of course, all this is very interesting stuff but I'm sure everyone has now formed their own opinions on whether the original reaction is a condensation.


It really dosen't matter -- for your information the C-C forming step is a Sn2 reaction not even you can deny it (though you are free to call it a condensation if you like), the formed salt is then liberated with a base -- again, call it a condensation if it makes you feel better. ;)




[Edited on 26-6-2006 by Sandmeyer]

unionised - 27-6-2006 at 09:30

"Sorry for posting that horrible sentence - but I'm an asshole and can't help it."
OK, that makes 2 of us. It seems that a whole bunch of reactions get called condensations. Some, but not all, meet the definition in the wiki article.

Now, does anyone actually know what the answer to the original question might be?