Mesomeric effect in -NHCOR and -OR

Question

I've read in Wikipedia about +M strength of groups which goes:

–O - > –NH2 > –NHCOR > –OR > –OCOR > –Ph > –CH3 > –F > –Cl > –Br > –I

Now in every other website states that in terms of +M strength:

website->brainly

website->Chemistry libretexts

(And many more)

My question:

Can you please verify the series and explain the reason if -OR actually has less activity than -NHCOR?

• Also since in -NH of -NHCOR there is an EWG(Electron withdrawing group) which is -COR which should decrease the +M strength of the group appreciably.

Answer 1

If you check out the $\mathrm{p}K_\mathrm{a}$ values of paracetamol (acetaminophen) , it is 9.38 while $\mathrm pK_\mathrm a$ of para-methoxybenzene is 10.1.

So, $\ce{-OR}$ should exert a greater mesomeric effect as compared to $\ce{-NHCOR}$ making the wikipedia wrong.

References:

1. https://pubchem.ncbi.nlm.nih.gov/compound/Acetaminophen

2. https://pubchem.ncbi.nlm.nih.gov/compound/4-Methoxyphenol#section=Ionicity

Answer 2

Hammett $\sigma_m$ and $\sigma_p$ constants are based upon the acid dissociation of benzoic acid and m- and p-substituted benzoic acids $(\ce{X-C6H4-CO2H})$ in water at $\pu{25 ^\circ C}$. They are correlated with $K_\mathrm{a}$ values of these benzoic acids as shown in few examples in the following table:

$$ \begin{array}{c|cccc} \hline \text{Substituent }(\ce{X}) & \sigma_p & K_\mathrm{a} & \mathrm{p}K_\mathrm{a} & \text{property} \\ \hline \ce{p-OCH3} & -0.27 & 3.5 \times 10^{-05} & 4.46 & \text{EDG} \\ \ce{p-CH3} & -0.17 & 4.3 \times 10^{-05} & 4.34 & \text{EDG} \\ \ce{H} & 0.00 & 6.46 \times 10^{-05} & 4.19 & \text{Standard} \\ \ce{p-Cl} & +0.23 & 1.10 \times 10^{-04} & 3.96 & \text{EWG} \\ \ce{p-NO2} & +0.78 & 3.90 \times 10^{-04} & 3.41 & \text{EWG} \\ \hline \end{array}\\ \text{Source: http://research.cm.utexas.edu/nbauld/unit4.htm} $$

It is safe to say that $\sigma_p$ constants are more reflected on mesomeric effect while $\sigma_m$ constants are more reflected on inductive effect (Ref.1).

Thus, let's look at some of $\sigma_p$ and $\sigma_m$ values:

$$ \begin{array}{c|cccc} \hline \text{Substituent }(\ce{X}) & \sigma_p & \sigma_m \\ \hline \ce{N(CH3)2} & -0.83 & -0.15 \\ \ce{NH2} & -0.66 & -0.16 \\ \ce{OH} & -0.37 & +0.12 \\ \ce{OCH3} & -0.27 & +0.12 \\ \ce{CH3} & -0.17 & -0.07 \\ \ce{NHC(=O)CH3} & -0.15 & +0.07 \\ \ce{C6H5}* & -0.01 & +0.06 \\ \ce{H} & 0.00 & 0.00 \\ \ce{OC(=O)Ph} & +0.13 & +0.21 \\ \ce{Cl} & +0.23 & +0.37 \\ \ce{C(=O)CH3} & +0.50 & +0.38 \\ \ce{NO2} & +0.78 & +0.71 \\ \hline \end{array}\\ \text{*: Indicates that the group is in the most sterically hindered conformation.}\\ \text{Source: Journal of Medicinal Chemistry Reference and others; see Ref.2 & 3 below} $$

According to $\sigma_p$ values, $+M$ strength of groups are:

$$\ce{-NH2 \gt -OH \gt -OR \gt -CH3 \gt -NH(C=O)R \gt -Ph \gt -OC(=O)R}$$

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References:

1. Corwin Hansch, Albert Leo, Robert W. Taft, "A survey of Hammett substituent constants and resonance and field parameters," Chem. Rev. 1991, 91(2), 165–195 (DOI: https://doi.org/10.1021/cr00002a004).
2. Corwin Hansch, Sharon D. Rockwell, Priscilla Y. C. Jow, Albert Leo, and Edward E. Steller, "Substituent Constants for Correlation Analysis," J. Med. Chem. 1977, 20(2), 304-306 (DOI: https://doi.org/10.1021/jm00212a024).
3. Corwin Hansch and Albert Leo, In Substituent Constants for Correlation Analysis in Chemistry and Biology; Wiley-Interscience: New York, NY, 1979 (ISBN-13: 978-0-471-05062-9).