[mana]

hi all
when an electron donationg group is on the benzyne ring how I can guess the regioselectivity of nucleophile attack? and also is it possible to see the benzyne mechanism in the rings with electron withdrawing groups?
I have seen these examples on a website, and I wonder how benzyne mechanism can occure with electron withdrawing groups

[mana]

??

[pgk]

1). The “triple” bond of the benzyne ring can be attacked from both sides by the nucleophile with simultaneous formation of an α-carbanion. Thus, it is possible to predict the regioselectivity of the nucleophile attack in presence either electron donating or electron withdrawing ring substituents by drawing the resonance structures in each case and tacking into account that a carbanion can be next to a carbocation but not next to a carbanion.
2). In general and due to kinetic reasons, electron donating substituents have strong directing properties in contrast to electron withdrawing ones that have weaker directing properties. Thus, mixtures of nucleophilic substitution products (but rich in the predicted product) are expected in case of electron withdrawing, ring substituents.

[spirochete]

It seems to be that benzyne mechanism happens if the group is only electron withdrawing by induction. This feels strange to me because CF3 is one of the strongest deactivators in EAS, which suggests it is similar withdrawing strength to nitro. But in the case of CF3/NaNH2, the benzyne mechanism still happens.

I do wonder why CF3 is so strongly withdrawing in EAS, but appears to be less withdrawing for NAS.

[pgk]

1). Activation/ deactivation of an aromatic ring by an electron donating/ withdrowing group, refers to the electrophilic aromatic substitution (EAS) kinetics; meaning that the EAS reaction rate has the order, e.g.:

Methoxybenzene > benzene > nitrobenzene

This happens because electron donating groups “push” the ring electrons by conjugation (I+ induction effect) and therefore, they favor (activate-accelerate) the electrophilic aromatic substitution (EAS); in contrast to electron donating/ withdrowing groups that "pull" the ring electrons by conjugation (I- induction effect) and therefore, they disfavor (desactivate - delay) the electrophilic aromatic substitution.
2). Although of the same origin (resconance induction effect), ortho-, para-/ meta substitution direction in EAS by electron donating/ withdrowing groups is due to the charge distribution of the ring atoms during conjugation and has nothing to do with the aromatic ring activation/ deactivation and the reaction rate.
3). Reasonably, activation/ deactivation of an aromatic ring by an electron donating/ withdrowing group in nucleophilic aromatic substitution (NAS) works in the inverse way; meaning that electron donating would delay NAS and electron withdrowing groups would accelarate NAS, respectively. However, benzyne is so instable and its formation is so fast that electron donating or electron withdrowing groups have a little influence in the NAS kinetics.
4). On the other hand, amide anion (sodamide) can attack to the methoxybenzyne only at the (kinetically favorable) para- position only, otherwise it will come close to the electronegative ortho- position.
But sodamide can attack to trifluoromethylbenzyne ring at the meta- position as coming close to the electropositive ortho- position, as well as at the para- position as forming a meta- carbanion next to the electropositive ortho- position and consequently, it further stabilizes the conjugation of the reaction intermediate.

[mana]

thanks for all replies, they were very usefull , now let me explain what I have understood from the answers and my searches on the literiture,
in the benzyne formation just inductive effect is important and resonance donating or withdrawing electron effect is no longer important. so it is possible  to see benzyne with some substituents like CF₃ or etc. also for prediction of nucleophilic attack regioselectivity, it depends on the substituent inductive effect and carbanion stability, if the substituent is electron withdrawing group (-I) thus nucleophile attack will happen on the carbon in which the negative charge is closer to EWG substituent.
 but now a new question:  what about electron donating groups (+I)? it has been written this rule is not for electron donating groups, so what should I do for them?

[pgk]

Please, read a more complete version, carefully:

“………..2). Although of the same origin (resconance induction effect), ortho-, para-/ meta substitution direction in EAS by electron donating/ withdrowing groups is due to the charge distribution of the ring atoms during conjugation and has nothing to do with the aromatic ring activation/ deactivation and the reaction rate (but someone can say that one way or another, activating groups are ortho-, para- directing and deactivating groups are meta- directing, only).

3). Reasonably, activation/ deactivation of an aromatic ring by an electron donating/ withdrowing group in nucleophilic aromatic substitution (NAS) works in the inverse way; meaning that electron donating would delay NAS and electron withdrowing groups would accelarate NAS, respectively. However, benzyne is so instable and its formation is so fast that electron donating or electron withdrowing groups have a little influence in the NAS kinetics (but still have).

4). On the other hand, amide anion (sodamide) can attack to the methoxybenzyne (methoxy- is a I+ inductive group) at the (kinetically favorable) para- position only, otherwise (= if attacking at the meta-position)  it would come close to the electronegative ortho- position (which is not favorable because similar charges repel each other).

But sodamide can attack to trifluoromethylbenzyne ring at the meta- position as coming close to the electropositive ortho- position (which is favorable because different charges attract each other), as well as at the para- position as forming a meta- carbanion next to the electropositive ortho- position and consequently, it further stabilizes the conjugation of the reaction intermediate.………….”

PS: Hoping that this version is more clarifying, I apologize if my text may give rise to a puzzle headache.

[mana]

4). On the other hand, amide anion (sodamide) can attack to the methoxybenzyne (methoxy- is a I+ inductive group) at the (kinetically favorable) para- position only, otherwise (= if attacking at the meta-position)  it would come close to the electronegative ortho- position (which is not favorable because similar charges repel each other).

But sodamide can attack to trifluoromethylbenzyne ring at the meta- position as coming close to the electropositive ortho- position (which is favorable because different charges attract each other), as well as at the para- position as forming a meta- carbanion next to the electropositive ortho- position and consequently, it further stabilizes the conjugation of the reaction intermediate.………….”

Thank you very much for your helps and your attention, but sorry I'M a little confused, this is the website which I have found these examples from that:

https://www.masterorganicchemistry.com/2018/09/17/nucleophilic-aromatic-substitution-2-arynes/#one

what do you mean exactly by different charges? I thought just a carbanion is formed here

[pgk]

What you see in the cited website, is a carbanion formation after the attack of NH2- to the benzyne.
Now, if you draw the resonance structure of the corresponding EWG substituted benzyne, (e.g. nitrobenzyne) before the NH2- attack, you will see a carbocation at the ortho- position, which attracts the opposite (= different) charge, which is the amide anion (NH2-) and forces it to pass nearby, attacking to the benzyne at the meta- position.
PS: Please, draw the resonance structures of the substituted benzynes, before trying to understand all the above.