Electrophilic aromatic directing groups
In
An electron donating group (EDG) or electron releasing group (ERG, Z in structural formulas) is an atom or
An electron withdrawing group (EWG) will have the opposite effect on the nucleophilicity of the ring. The EWG removes electron density from a π system, making it less reactive in this type of reaction,[2][3] and therefore called deactivating groups.
EDGs and EWGs also determine the positions (relative to themselves) on the aromatic ring where substitution reactions are most likely to take place. Electron donating groups are generally ortho/para directors for electrophilic aromatic substitutions, while electron withdrawing groups (except the halogens) are generally meta directors. The selectivities observed with EDGs and EWGs were first described in 1892 and have been known as the Crum Brown–Gibson rule.[4]
Categories
Electron donating groups are typically divided into three levels of activating ability (The "extreme" category can be seen as "strong".) Electron withdrawing groups are assigned to similar groupings. Activating substituents favour electrophilic substitution about the ortho and para positions. Weakly deactivating groups direct
Activating groups
The activating groups are mostly resonance donors (+M). Although many of these groups are also inductively withdrawing (–I), which is a deactivating effect, the resonance (or mesomeric) effect is almost always stronger, with the exception of Cl, Br, and I.
Magnitude of
activation |
Substituent Name (in approximate order
of activating strength) |
Structure | Type of electronic effect | Directing effect |
---|---|---|---|---|
Extreme | oxido group | -O− | +I, +M, metal-hydrogen exchange | ortho, para |
Strong | (substituted) amino groups | -NH2, -NHR, -NR2 | –I, +M | |
hydroxy and alkoxy groups | -OH,
-OR | |||
Moderate | acylamido groups | -NHCOR | ||
acyloxy groups | -OCOR | |||
alkylthio, and sulfhydryl groups[6]
|
-PR2,
-SR, -SH |
+M (weak) | ||
Weak | phenyl (or aryl) group
|
-C6H5 | –I, +M;[7][8] though other interactions may be involved as well[9] | |
vinyl group | -CH=CH2 | |||
alkyl groups
(e.g. -CH3, -C2H5) |
-R | |||
carboxylate group[10] | -CO2− | +I |
In general, the resonance effect of elements in the
Due to a stronger resonance effect and inductive effect than the heavier halogens, fluorine is anomalous. The partial rate factor of electrophilic aromatic substitution on fluorobenzene is often larger than one at the para position, making it an activating group.[11] Conversely, it is moderately deactivated at the ortho and meta positions, due to the proximity of these positions to the electronegative fluoro substituent.
Deactivating groups
While all deactivating groups are inductively withdrawing (–I), most of them are also withdrawing through resonance (–M) as well. Halogen substituents are an exception: they are resonance donors (+M). With the exception of the halides, they are meta directing groups.
Halides are ortho, para directing groups but unlike most ortho, para directors, halides mildly deactivate the arene. This unusual behavior can be explained by two properties:
- Since the halogens are very electronegative they cause inductive withdrawal (withdrawal of electrons from the carbon atom of benzene).
- Since the halogens have non-bonding electrons they can donate electron density through pi bonding (resonance donation).
The inductive and resonance properties compete with each other but the resonance effect dominates for purposes of directing the sites of reactivity. For nitration, for example, fluorine directs strongly to the para position because the ortho position is inductively deactivated (86% para, 13% ortho, 0.6% meta). On the other hand, iodine directs to ortho and para positions comparably (54% para and 45% ortho, 1.3% meta).[12]
Magnitude of
deactivation |
Substituent Name (in approximate order
of deactivating strength) |
Structure | Type of electronic effect | Directing effect |
---|---|---|---|---|
Strong | trifluoromethylsulfonyl group[13]
|
-SO2CF3 | –I, –M | meta |
(substituted) ammonium groups[14] | -NR3+ (R = alkyl or H) | –I | ||
nitro group | -NO2 | –I, –M | ||
sulfonyl groups
|
-SO3H,
-SO2R | |||
cyano group | -C≡N | |||
-CF3 group )
|
-CX3 (X = F, Cl, Br, I) | –I | ||
Moderate | haloformyl groups
|
-COX
(X = Cl, Br, I) |
–I, –M | |
formyl and acyl groups | -CHO,
-COR | |||
carboxyl and alkoxycarbonyl groups | -CO2H,
-CO2R | |||
(substituted) aminocarbonyl groups | -CONH2,
-CONHR, -CONR2 | |||
Weak | fluoro group (ortho, meta positions)
|
-F | –I, +M (ortho) | ortho, para |
nitroso group | -N=O | –I, +M (dimer) or
–M (monomer) | ||
halo groups
|
-F(para), -Cl, -Br, -I[15] | –I, +M (weak) |
Traditional rationalizations
Although the full electronic structure of an arene can only be computed using quantum mechanics, the directing effects of different substituents can often be guessed through analysis of resonance diagrams.
Specifically, any formal negative or positive charges in minor resonance contributors (ones in accord with the natural polarization but not necessarily obeying the octet rule) reflect locations having a larger or smaller density of charge in the molecular orbital for a bond most likely to break. A carbon atom with a larger coefficient will be preferentially attacked, due to more favorable orbital overlap with the electrophile.[16]
The perturbation of a conjugating electron-withdrawing or electron-donating group causes the π electron distribution on a benzene ring to resemble (very slightly!) an electron-deficient benzyl cation or electron-excessive benzyl anion, respectively. The latter species admit tractable quantum calculation using Hückel theory: the cation withdraws electron density at the ortho and para positions, favoring meta attack, whereas the anion releases electron density into the same positions, activating them for attack.[17] This is precisely the result that the drawing of resonance structures would predict.
For example, aniline has resonance structures with negative charges around the ring system:
Attack occurs at ortho and para positions, because the (partial) formal negative charges at these positions indicate a local electron excess. On the other hand, the nitrobenzene resonance structures have positive charges around the ring system:
Attack occurs at the meta position, since the (partial) formal positive charges at the ortho and para positions indicate electron deficiency at these positions.
Another common argument, which makes identical predictions, considers the stabilization or destabilization by substituents of the Wheland intermediates resulting from electrophilic attack at the ortho/para or meta positions. The Hammond postulate then dictates that the relative transition state energies will reflect the differences in the ground state energies of the Wheland intermediates.[14][18]
Carbonyls, sulfonic acids and nitro
Because of the full or partial positive charge on the element directly attached to the ring for each of these groups, they all have a moderate to strong electron-withdrawing inductive effect (known as the -I effect). They also exhibit electron-withdrawing resonance effects, (known as the -M effect):
Thus, these groups make the aromatic ring very electron-poor (δ+) relative to benzene and, therefore, they strongly deactivate the ring (i.e. reactions proceed much slower in rings bearing these groups compared to those reactions in benzene.)
Anilines, phenols, and ethers (such as anisole)
Due to the electronegativity difference between carbon and oxygen / nitrogen, there will be a slight electron withdrawing effect through inductive effect (known as the –I effect). However, the other effect called resonance add electron density back to the ring (known as the +M effect) and dominate over that of inductive effect. Hence the result is that they are EDGs and ortho/para directors.
Phenol is an ortho/para director, but in a presence of base, the reaction is more rapid. It is due to the higher reactivity of
Alkyl groups
Carboxylate
Inductively, the negatively charged carboxylate ion moderately repels the electrons in the bond attaching it to the ring. Thus, there is a weak electron-donating +I effect. There is an almost zero -M effect since the electron-withdrawing resonance capacity of the carbonyl group is effectively removed by the delocalisation of the negative charge of the anion on the oxygen. Thus overall the carboxylate group (unlike the carboxyl group) has an activating influence.[10]
Alkylammonium and trifluoromethyl group
These groups have a strong electron-withdrawing inductive effect (-I) either by virtue of their positive charge or because of the powerfully electronegativity of the halogens. There is no resonance effect because there are no orbitals or electron pairs which can overlap with those of the ring. The inductive effect acts like that for the carboxylate anion but in the opposite direction (i.e. it produces small positive charges on the ortho and para positions but not on the meta position and it destabilises the
Halides' competing effects
Induction versus resonance
Fluorine is something of an anomaly in this circumstance. Above, it is described as a weak electron withdrawing group but this is only partly true. It is correct that fluorine has a -I effect, which results in electrons being withdrawn inductively. However, another effect that plays a role is the +M effect which adds electron density back into the benzene ring (thus having the opposite effect of the -I effect but by a different mechanism). This is called the mesomeric effect (hence +M) and the result for fluorine is that the +M effect approximately cancels out the -I effect. The effect of this for fluorobenzene at the para position is reactivity that is comparable to (or even higher than) that of benzene. Because inductive effects depends strongly on proximity, the meta and ortho positions of fluorobenzene are considerably less reactive than benzene. Thus, electrophilic aromatic substitution on fluorobenzene is strongly para selective.
This -I and +M effect is true for all halides - there is some electron withdrawing and donating character of each. To understand why the reactivity changes occur, we need to consider the
Notice that iodobenzene is still less reactive than fluorobenzene because
Directing effect
Due to the lone pair of electrons, halogen groups are available for donating electrons. Hence they are therefore ortho / para directors.
Nitroso group
Induction
Due to the electronegativity difference between carbon and nitrogen, the nitroso group has a relatively strong -I effect, but not as strong as the nitro group. (Positively charged nitrogen atoms on alkylammonium cations and on nitro groups have a much stronger -I effect)
Resonance
The nitroso group has both a +M and -M effect, but the -M effect is more favorable.
Nitrogen has a lone pair of electrons. However, the lone pair of its monomer form is unfavourable to donate through resonance. Only the dimer form is available for +M effect. However, the dimer form is less stable in a solution. Therefore, the nitroso group is less available to donate electrons.
Oppositely, withdrawing electron density is more favourable: (see the picture on the right).
As a result, the nitroso group is a deactivator. However, it has available to donate electron density to the benzene ring during the Wheland intermediate, making it still being an ortho / para director.
Steric effects
There are 2 ortho positions, 2 meta positions and 1 para position on benzene when a group is attached to it. When a group is an ortho / para director with ortho and para positions reacting with the same partial rate factor, we would expect twice as much ortho product as para product due to this statistical effect. However, the partial rate factors at the ortho and para positions are not generally equal. In the case of a fluorine substituent, for instance, the ortho partial rate factor is much smaller than the para, due to a stronger inductive withdrawal effect at the ortho position. Aside from these effects, there is often also a steric effect, due to increased steric hindrance at the ortho position but not the para position, leading to a larger amount of the para product.
The effect is illustrated for electrophilic aromatic substitutions with alkyl substituents of differing steric demand for electrophilic aromatic nitration.[19]
Substrate | toluene [-CH3] | ethylbenzene
[-CH2CH3] |
cumene
[-CH(CH3)2] |
tert-butylbenzene
[-C(CH3)3] |
---|---|---|---|---|
ortho product | 58 | 45 | 30 | 16 |
meta product | 5 | 6 | 8 | 11 |
para product | 37 | 59 | 62 | 73 |
ortho/para ratio | 1.57 | 0.76 | 0.48 | 0.22 |
The methyl group in toluene is small and will lead the ortho product being the major product. On the other hand, the t-butyl group is very bulky (there are 3 methyl groups attached to a single carbon) and will lead the para product as the major one. Even with toluene, the product is not 2:1 but having a slightly less ortho product.
Directing effect on multiple substituents
When two substituents are already present on the ring, the third substituent's new location is relatively predictable. If the existing substituents reinforce or the molecule is highly symmetric, there may be no ambiguity. Otherwise:[20]
- The most-activating substituent usually controls over the less-activating one.
- In particular, ortho/para directors control over meta ones.
- When multiple substituents are comparably activating, steric hindrance dominates regioselectivity.
- In particular, the position between two substituents, each meta to the other, reacts last.
See also
References
- ^ "Electron withdrawing group". Illustrated Glossary of Organic Chemistry. UCLA Department of Chemistry. Retrieved 16 November 2012.
- ^ a b Hunt, Ian. "Substituent Effects". University of Calgary Department of Chemistry. Retrieved 16 November 2012.
- ^ "Electron donating group". Illustrated Glossary of Organic Chemistry. UCLA Department of Chemistry. Retrieved 16 November 2012.
- .
- ^ "Substituent Effects". www.mhhe.com. Retrieved 2 April 2015.
- ^ James, Ashenhurst (29 Jan 2018). "Ortho-, Para- and Meta- Directors in Electrophilic Aromatic Substitution". Master Organic Chemistry.
- ISBN 9780748761623.
- S2CID 46641895.
- OCLC 205846.
- ^ a b Smith, Ed (12 February 2018). "LECTURE 2" (PDF). Handouts for Organic Chemistry Lectures given at Imperial College London, Chemistry. p. 3.
- ISSN 0021-9584.
- ^ OCLC 761379371.
- .
- ^ OCLC 1007924903.)
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: CS1 maint: location missing publisher (link) CS1 maint: multiple names: authors list (link - ^ "Substitution Reactions of Benzene Derivatives". Chemistry LibreTexts. 2013-10-02. Retrieved 2021-09-18.
- )
- OCLC 2048204.
- )
- ISBN 0851869998.
- ^ "12.15. Multiple Multiple Substituent Substituent Effects" (PDF). p. 7.