Hi

I am interested in organic chemistry Can someone tell me if

https://en.m.wikipedia.org/wiki/Cytosine

is a ketone between the N and NH

I thought to be a ketone the connected substituents had to be carbon containing as per

https://en.m.wikipedia.org/wiki/Ketone

Hi

I am interested in organic chemistry Can someone tell me if

https://en.m.wikipedia.org/wiki/Cytosine

is a ketone between the N and NH

I thought to be a ketone the connected substituents had to be carbon containing as per

https://en.m.wikipedia.org/wiki/Ketone

I agree. It's a carbonyl group, sure, but it's an amide rather than a ketone, I should have thought, as the carbonyl is joined to N. Though perhaps not a real amide, since the lone pair on the NH group may be participating in the aromatic ring structure, i.e. sp2 hybridised, which would not be the case with a regular amide.

Mind you, it's not clear to me whether cystosine really is aromatic. It seems to me it would only be aromatic if the carbonyl is strongly polarised, to C⁺-O⁻ , since for aromaticity you would want only 6 electrons in the π system (Hückel's Rule). But I'm very rusty on this stuff. Maybe someone more up to date can comment.

Cytosine has keto and enol forms that rapidly exchange by polytropic tautomerisation.

The keto form is the only form shown in the Wiki article.

1 hour ago, studiot said:

Cytosine has keto and enol forms that rapidly exchange by polytropic tautomerisation.

The keto form is the only form shown in the Wiki article.

Ah yes of course, the enol form will be aromatic while the keto one is not.

R-(C=O)-R' is called ketone if R,R' is alkyl or aryl.

CH3COCH2CH3 Butanone

If R,R' is an O then it's an ester

CH3CO-OCH3 Methylacetate

(CH3CO)2CO Dimethylcarbonate

and R,R' is N then it's an amid, special an urea derivate in the case of cytosine.

NH2CONH2 urea

CH3CON(CH3)2 Dimethylacetamid

Edited April 14Apr 14 by chenbeier

Just now, chenbeier said:

R-(C=O)-R' is called ketone if R,R' is alkyl or aryl.

If R,R' is O then it's a ester and R,R' is N then it's a Amid, special an urea derivate.

This is the case in cytosine.

Your memory is more complete than mine. +1

Looking at the image in @studiot 's post, one thing that I see is notable is that whereas cytosine enolises to an aromatic hydroxy compound, the attachment of the deoxyribose to the nitrogen atom "freezes" the molecule in the non-aromatic keto form.

1 hour ago, KJW said:

"freezes" the molecule in the non-aromatic keto form.

Given the resonance structures N–C=O <—> ⁺N=C–O^– , even with the deoxyribose attached the cytosine ring should still be aromatic (and planar).

Edited April 14Apr 14 by KJW

On 4/14/2025 at 5:10 PM, KJW said:

Given the resonance structures N–C=O <—> ⁺N=C–O^– , even with the deoxyribose attached the cytosine ring should still be aromatic (and planar).

Yes. But surely only the second, zwitterionic structure would support aromaticity, as the neutral keto form has 7 electrons in the ring π-system, (plus one more on the oxygen atom). So one might expect there to be quite strong polarisation of the keto form, which would presumably favour the rearrangement to the enol form. However I read that the keto form is the more stable, which seems a bit paradoxical. What about the NMR? Should be ring currents if it is aromatic.

I suppose what we need here is an MO diagram.

Edited April 16Apr 16 by exchemist

@exchemist

I've been looking at N-methyl-2-pyridone as an analogue of the N-substituted cytosine. The ¹H-NMR spectrum has the following chemical shifts:

H3 = 6.17

H4 = 7.34

H5 = 7.32

H6 = 6.57

HMe = 3.59

(https://www.chemicalbook.com/SpectrumEN_694-85-9_1HNMR.htm)

Compare with benzene = 7.34 (https://en.wikipedia.org/wiki/Benzene_(data_page))

Compare with trimethylamine = 2.12 (https://docbrown.info/page06/spectra2/trimethylamine-nmr1h.htm)

Compare with tetramethylammonium iodide = 3.207 (https://www.chemicalbook.com/spectrumen_75-58-1_1hnmr.htm)

Compare with HMe of toluene = 2.32 (https://en.wikipedia.org/wiki/Toluene_(data_page))

Compare with HMe of methylcyclohexane = 0.858 (https://www.chemicalbook.com/SpectrumEN_108-87-2_1HNMR.htm)

The chemical shifts of the ring protons of N-methyl-2-pyridone, being similar to benzene, do suggest a ring current associated with aromaticity. I also compared the methyl protons of N-methyl-2-pyridone to the protons of the methyl group attached to the uncharged nitrogen of trimethylamine and the charged nitrogen of tetramethylammonium iodide. However, this is complicated by ring current effects which led me compare the methyl protons of toluene and methylcyclohexane.

On thing worth noting is that the oxygen atom of phenol and especially of the phenoxide ion is electron-donating to the 2, 4, and 6 positions. This is similar to the tendency for N-methyl-2-pyridone to be in the pyridone electronic configuration. Similarly, pyridine and especially the pyridinium ion is electron-withdrawing from the 2, 4, and 6 positions, also leading to the tendency for N-methyl-2-pyridone to be in the pyridone electronic configuration. However, I suspect that N-methyl-2-pyridone is still aromatic.

3 minutes ago, KJW said:

N-methyl-2-pyridone, Yes, N-methyl-2-pyridone is an aromatic compound. It's a member of the nicotinamide class of heterocyclic aromatic compounds.