Question

When semicarbazide reacts with a ketone (or aldehyde) to form semicarbazone. Only one nitrogen atom of semicarbazide acts as a nucleophile and attacks the carbonyl carbon of the ketone. The product of the reaction consequently is ${{R}_{2}}C=N-NH-CON{{H}_{2}}$ rather than ${{R}_{2}}C=NCONH-N{{H}_{2}}.$ What factors account for the fact that two nitrogen atoms of semicarbazide are relatively non-nucleophilic?

Answer 1

Nucleophiles such as $N{{H}_{3}}$ or its derivatives can add to the carbonyl group of ketones and aldehydes to give nitrogen-substituted derivatives. The addition of nucleophiles changes the hybridization of the carbon center from $s{{p}^{2}}$ to $s{{p}^{3}}$ and an intermediate is formed which gets neutralized further to give the product.

Complete step by step solution:
We know that aldehydes and ketones are carbonyl compounds as they contain $N{{H}_{3}}$ group. Due to the difference in the electronegativity, $>C=O$ bond can be shown as $>{{C}^{\delta +}}={{O}^{\delta -}}$
We know that electrophiles are those which can accept electrons as carbon centers in $>{{C}^{\delta +}}={{O}^{\delta -}}$ . This electrophilic center can be attacked by a variety of nucleophiles such as cyanide ions or ammonia. Here, we will take the nucleophilic addition of ammonia to a carbonyl group which can be explained as follows:
For example, hydroxylamine can give oxime and hydrazine can give a hydrazone. When a semicarbazide is added to the carbonyl group of ketones or aldehydes, the product is called semicarbazone. Let’s have a look at the semicarbazide addition to cyclobutanone.
$\left( {{H}_{3}}C-CH=O \right)+\left( {{H}_{2}}N-NH-CON{{H}_{2}} \right)\xrightarrow{{{H}^{\oplus }}}\left( {{H}_{3}}C-CH=N-NCO\ddot{N}{{H}_{2}} \right)+{{H}_{2}}O$
As we can see that electrophilic centers are created at carbon by protonation of oxygen atoms. The lone pair of electrons on nitrogen in semicarbazide is accepted by the electrophilic carbon of cyclobutanone giving a positive charge to the nitrogen. The neutrality is gained by removal of a proton to give the addition intermediate. This intermediate readily loses water to give the final product which is called semicarbazone.

Note:
Derivatives of ammonia can also be used in place of ammonia to give the corresponding nitrogen substituted derivatives. A semicarbazone is a derivative of imines formed by a condensation reaction between a ketone or aldehyde and semicarbazide.