[lip]

1)
Can anyone tell me the reason for protonation of carbonyl oxygen first in acid catalyzed hydration of amide or esters instead of nitrogen or other oxygen.Is this due to basicity difference? if so how come cabonyl oxygen is more basic than others.

2)
what are the benifit of using ethyl acetoacetate instead of acetone in methyl keton synthesis.

[Dan]

Is this due to basicity difference? if so how come cabonyl oxygen is more basic than others.

Yes. Hint: Resonance.

2) what are the benifit of using ethyl acetoacetate instead of acetone in methyl keton synthesis.

This is to do with the ease of enolate formation.

[orgopete]

1)
Can anyone tell me the reason for protonation of carbonyl oxygen first in acid catalyzed hydration of amide or esters instead of nitrogen or other oxygen.Is this due to basicity difference? if so how come cabonyl oxygen is more basic than others.

2)
what are the benifit of using ethyl acetoacetate instead of acetone in methyl keton synthesis.

1) Because of how this question has been asked, I am going to give a different answer. Let me explain. In the hydrolysis of an amide or ester, a direct substitution does not occur on a carbonyl carbon. An addition-elimination must take place. In order for this mechanism to take place, the sp2 atom must be protonated so addition will result. Those are the requirements for writing a successful mechanism.

Wouldn't one expect an sp3 nitrogen to be more basic? I think so. Protonation upon the nitrogen would be consistent with a greater electron withdrawing properties of sp and sp2 atoms. However, it will not be on the hydrolysis pathway.

I argue the protonation sites are consistent with the facile decarboxylation of bicarbonate or dehydration of nitrous acid. Because proton transfer reaction in protic solvents are very fast, I am only agreeing with this point on theoretical grounds. The mechanism for hydrolysis requires protonation of the sp2 atom.

2) Calculate fraction of enol formation with ethoxide for each.

[Dan]

Wouldn't one expect an sp3 nitrogen to be more basic? I think so. Protonation upon the nitrogen would be consistent with a greater electron withdrawing properties of sp and sp2 atoms. However, it will not be on the hydrolysis pathway.

The N in (most) amides is sp² hybridised, not sp³. There is experimental and computational evidence supporting the textbook description of the amide O (usually) being more basic than the amide N. I am not intimately familiar with this literature, but here are a couple of papers:

http://pubs.acs.org/doi/abs/10.1021/ja01502a010
http://www.nrcresearchpress.com/doi/abs/10.1139/v63-019#.UV2j7JOG2vM
http://pubs.acs.org/doi/abs/10.1021/ja01004a034
http://pubs.acs.org/doi/abs/10.1021/ja0663024

[orgopete]

Wouldn't one expect an sp3 nitrogen to be more basic? I think so. Protonation upon the nitrogen would be consistent with a greater electron withdrawing properties of sp and sp2 atoms. However, it will not be on the hydrolysis pathway.

The N in (most) amides is sp² hybridised, not sp³. There is experimental and computational evidence supporting the textbook description of the amide O (usually) being more basic than the amide N. I am not intimately familiar with this literature, but here are a couple of papers:

http://pubs.acs.org/doi/abs/10.1021/ja01502a010
http://www.nrcresearchpress.com/doi/abs/10.1139/v63-019#.UV2j7JOG2vM
http://pubs.acs.org/doi/abs/10.1021/ja01004a034
http://pubs.acs.org/doi/abs/10.1021/ja0663024

Agreed! I should read my own book.

[lip]

 Dan and orgopete

Thank you very much for your answers.  .