[wilson]

Hi all, I was wondering:
In SN1/SN2 reactions, the leaving group is usually one that is not very basic and is also "less nucleophilic" than the nucleophile, esp. in SN2 reactions here the nucleophilicity of the nucleophile is crucial. E.g. -OH will substitute over -Cl, -Cl will substitute over -NO2

Then, in SNAr (addition elimination), let's say we have m-nitrochlorobenzene and we chlorinate it. Why will the Cl substitute on H instead of NO2 even though NO2 is an excellent leaving group and a poorer nucleophile than Cl? Does this have anything to do with the fact that NO2 is an activator because it is electron withdrawing?

Could someone please clarify?

[english]

Hi all, I was wondering:
In SN1/SN2 reactions, the leaving group is usually one that is not very basic and is also "less nucleophilic" than the nucleophile

Don't think of it that way.  A leaving group is not nucleophilic in a substitution rxn.

Then, in SNAr (addition elimination), let's say we have m-nitrochlorobenzene and we chlorinate it. Why will the Cl substitute on H instead of NO2 even though NO2 is an excellent leaving group and a poorer nucleophile than Cl?

Are you sure?  I'm asking.  I've always wondered if a nitro group is a better group than Cl, because of its postively charged nitrogen.   I'm not sure this is enough to be better.

Does this have anything to do with the fact that NO2 is an activator because it is electron withdrawing?

A nitro group is not activating!

[wilson]

Don't think of it that way.  A leaving group is not nucleophilic in a substitution rxn.

But come to think about it, the nucleophile in any nucleophilic substitution needs to be more nucleophilic in nature compared to leaving group. Well, I haven't seen any SN where for example a weaker nucleophile such as NO2 will substitute and displace a stronger nucleophile Cl. I am not sure here, but I haven't seen any.

Are you sure?  I'm asking.  I've always wondered if a nitro group is a better group than Cl, because of its postively charged nitrogen.   I'm not sure this is enough to be better.

I doubt a nitro group can be substituted by chlorine. I gave meta-nitrochlorobenzene as an example because I happened to pass by another thread "formation of 1,3-dichlorobenzene". They were mentioning about how to go about transforming m-nitrochlorobenzene to m-dichlorobenzene by the Sandmeyer Rxn.

A nitro group is not activating!

I thought the nitro group is deactivating in Electrophilic Aromatic Substitutions but activating in Nucleophilic ones. The reverse holds true right?


So yet I am still wondering why will Cl substitute on the hydrogen of m-nitrochlorobenzene instead of the nitro group. What's the theoretical reason? I am getting sort of confused now.

[Yggdrasil]

Hi all, I was wondering:
In SN1/SN2 reactions, the leaving group is usually one that is not very basic and is also "less nucleophilic" than the nucleophile

Don't think of it that way.  A leaving group is not nucleophilic in a substitution rxn.

Actually, I think this is a great way to think of a lot of substitution reactions.  Given nucleophies Y and Z with parent compound X, you have the following equilibrium:

X-Y + Z <--> X-Z + Y

Where the equilibrium favors the side with the better leaving group/worse nucleophile being free.

As for why the nitro group is not kicked off, I think the conjugation between the nitro group's pi system and the benzene ring helps strengthen the N-C bond.

[english]

Yes I'm sorry wilson I forgot we were talking of S_NAr.  Nitro groups deactivate the ring, allowing the nucleophile to approach the side.  Without a strongly deactivating group, a nucleophile could not approach the ring due to the electron density of the pi cloud.

You are correct.  My mistake.


I also just prefer to think of the whole process by comparing basicities, not nucleophilic character.  Either way is correct, but I prefer this way as it is less confusing, allowing you to focus on the intermedate as a disubsituted benzene with two leaving groups.  This is called a Meisenheimer complex.

Either way it's the same thinking!   

[movies]

I also just prefer to think of the whole process by comparing basicities, not nucleophilic character.  Either way is correct, but I prefer this way as it is less confusing, allowing you to focus on the intermedate as a disubsituted benzene with two leaving groups.  This is called a Meisenheimer complex.

This is not exactly correct!  Nucleophilicity and basicity are very different effects.  One is a kinetic effect, the other an equillibrium effect.  For example, take azide compared to triethylamine.  Azide is a much better nucleophile, but its conjugate acid has a low pK_a (~5) while the opposite is true of triethylamine (pK_a of conjugate acid = 11).

As to the question at hand, to do S_NAr chemistry, you almost always need an electron withdrawing group (such as nitro) because the rate limiting step is attack of the nucleophile onto the aromatic ring.  If you were to do this at the carbon ipso to the nitro group, you wouldn't get any stabilization of the anion you generate.  If you think of the attack as a conjugate addition, so then at the position ortho to the nitro group, then you can delocalize the charge onto the withdrawing group.  Subsititution of the Cl in meta-nitrochlorobenzene would be very slow because the meta position isn't activated toward nucleophilic attack.

[wilson]

Thanks, everyone for your helpful replies. Still have some queries:

Subsititution of the Cl in meta-nitrochlorobenzene would be very slow because the meta position isn't activated toward nucleophilic attack.

Why is the meta position deactivated? Does this have anything to do with the electron density? I don't see why so because Cl is electronegative. Or is it because charges of the intermediate cannot be delocalized and stabilized?

In the end, if i were to chlorinate m-nitrochlorobenzene, I will probably get 1,2,3-nitrodichlorobenzene. Right?

This is not exactly correct!  Nucleophilicity and basicity are very different effects.  One is a kinetic effect, the other an equillibrium effect.

Just to ask, are there any general relations between nucleophiles, leaving groups and basicity?
Is a good leaving group a weak base?
Is a good nucleophile a strong base?

How do we determine how good a nucleophile is? Is using the nucleophilicity scales the only way of determination?

[english]

wilson,

movies means that in the meta position, the delocalized anion cannot delocalize into the nitro group if the nitro group is at the meta position.


Try this.  Draw m-chloronitrobenzene, then perform an S_NAr reaction.  Guaranteed, you will not get that lone pair on the nitro group when it is at the meta position with respect to the chlorine.

At the ortho and para positons, on the other hand, the lone pair can in fact delocalize onto the nitro group.

[wilson]

Ok, so it's the delocalization of electrons to the EWG to form a stable intermediate anion resonance.

Subsititution of the Cl in meta-nitrochlorobenzene would be very slow because the meta position isn't activated toward nucleophilic attack.

If that's the case, then substitution should never take place at all (0%).

Thanks guys, for all your help. (:

[movies]

Yes, I agree that reaction would probably be far too slow to be useful.  I hate to say it would never happen though!

As for nucleophilicity versus basicity, actual quantifications of these effects aren't as important as the relative properties of different molecules.  Take my azide/triethylamine example: you can pretty easily rationilize why one would be a good base but a poor nucleophile based on sterics.  Most cases are like this, so it's not all that hard.  The thing you need to remember is that the two effects are different.

I think of them this way: basicity (pK_a) is an equillibrium measurement.  You would put your molecule in a solvent, let it sit for a while, and measure how much is dissociated.

Nucleophilicity, on the other hand, is a kinetic question.  In two nucleophilic displacement reactions the products are essentially the same, so they are likely similar endpoints, thermodynamically speaking.  The difference we might expect to observe is which nucleophile reacts faster.  A really great nucleophile could react in seconds, while a poor nucleophile might take ages.

[english]

wilson,

the deactivation process in the Meisenheimer complex is more of a matter of enabling the nucleophile to better approach the ring.

Pi clouds are very restricting on nucleophiles and how well they displace leaving groups.  In this case we have an aryl halide, chlorobenzene.


The only way to make this reaction go is to have a strong or many moderate deactivators, to "suck" the electron density away from the site of nucleophilic attack.



You can actually see the experimental conditions of this reaction and how they change of we have one nitro group, two, and then three.

The aryl halide with three nitro groups takes considerably less harsh conditions to run.

[AhmedEzatAlzawalaty]

the chlorine walks away since it has good leaving ability like nitro but nitro not leaves i think becoz it would be involved in stabilizing the ring in the sigma complex intermediate better than chlorine .the former has mesomeric effect better then the latter.

[Custos]

Just to ask, are there any general relations between nucleophiles, leaving groups and basicity?
Is a good leaving group a weak base?
Is a good nucleophile a strong base?

How do we determine how good a nucleophile is? Is using the nucleophilicity scales the only way of determination?

The short answer is not necessarily, and it's not even as simple as that. In fact how "good" a nucleophile is also depends on the electrophile. To get a better understanding I suggest you do some reading on the hard and soft acid/base theory. It applies to nucleophilic reactions as well. eg.:

Ralph Pearson and Jon Songstad published a highly cited JACS paper, ranked 124th, that focused on application of the HSAB principle to organic chemistry [J. Am. Chem. Soc., 89, 1827 (1967)]. In a nucleophilic substitution reaction in which one Lewis base replaces another, for example, if the acid site is hard, then softness (polarizability) in the nucleophile will not provide a high rate of reaction. If the acid is soft, then a soft nucleophile will react more quickly.

[english]

Maybe an example would help.

Chloride is a good nucleophile in DMF, or DMSO, but really poor in water or an alcohol.

In those cases even the poorest nucleophiles would be better than chloride.

[wilson]

Maybe an example would help.

Chloride is a good nucleophile in DMF, or DMSO, but really poor in water or an alcohol.

In those cases even the poorest nucleophiles would be better than chloride.

This is because DMF and DMSO are aprotic polar solvents while water and alcohol and protic polar solvents right?