[Robin]

Hi there,

Ive been struggling with this problem for a while now and can't find any decent explanations. Diazotization of an aromatic amine yields the unstable diazonium salt and upon heating N₂ gas is released, forming an aryl carbocation. My question is why then will a halide anion such as Cl^- add directly to this cation? why are Cu(I) salts necessary? From my research on the reaction it appears that it involves radical intermediates. I understand the mechanism and from what i understand the use of the radical mediated reaction is used to form an aryl radical, which will then react with the Cu(II) halide , halogenating the aromatic ring with a halogen radical and reforming the Cu(I) halide. So is this done to avoid the carbocation intermediate which could react with water formed during the reaction or other constituents of the solution?

If this is the case, why then can KI add to the diazonium salt without the need for a copper catalyst? is it because Iodine can form a radical more easily allowing the radical pathway?

Any help on this subject would be greatly appreciated, Thank you for your time.

[pgk]

Due to conjugation, aromatic carbocation is a borderline acid that prefers to react with water (reaction medium) which is a soft base instead of F- , Cl- and Br- that are hard bases (Br- is rather a borderline base) but it can easily react with I- which is a soft base.
Please, take a look to the Pearson’ s hard/soft acids and bases classification.

[orgopete]

Due to conjugation, aromatic carbocation is a borderline acid that prefers  to react with water (reaction medium) which is a soft base instead of F- , Cl- and Br- that are hard bases (Br- is rather a borderline base) but it can easily react with I- which is a soft base.
Please, take a look to the Pearson’ s hard/soft acids and bases classification.

This would not seem to be the answer as these reactions are carried out in water and phenols are rather more difficult to prepare.

[pgk]

Thanks for the suggestions, Orgopette.
Better written:
Due to conjugation, aromatic carbocation is a borderline acid that prefers to react with water that is the reaction medium (because these reactions are carried out in water) and is a soft base, instead of F- , Cl- and Br- that are hard bases (Br- is rather a borderline base) but it can easily react with I- which is a soft base.
According to the “Vogel’s Textbook of organic Chemistry”, phenols do not seem not so difficult to prepare with excellent yields, by the Sandmayer reaction and a farther acidification with H2SO4 that stabilizes the aromatic carbocation. Of course in certain cases, the hardness or softness of aromatic carbocation also depends on the electron donor/attracting substituents,as well as their position on the aromatic ring.   

[phth]

This guy proceeds by Single Electron Transfer mechanism not cation. Iodine is good at SET accepting into its LUMO.  Phenol can be made 100% yield from benzene. Radicals are more stable in aromatic solvents because they do not tunnel as much.  Cl· in benzene bounces off the aromatic pi orbitals on the order of 10^-12s.  http://cdn.name-reaction.com/assets/_reaction_images/_png/sandmeyer-reaction-m-aba3db08fd457c99e0a770dd43ef07f0.png 
The Cu is used because it provides a different mechanism than cation which is exactly how it catalyzes the reaction through lowering the SET pathway below cationic formation. Cu(I) because it can easily donate an electron.

[pgk]

During diazonium salt preparation, the temperature must be kept bellow 5oC, otherwise gaseous nitrogen will be released; while during Sandmayer coupling, the temperature is raised up and sometimes, even up to boiling (e.g. phenol preparation}.
Question: Does the formation of gaseous nitrogen occurs via electron transfer or via carbocation formation?
PS: What you see in the above link, is the representation of the catalytic cycle of copper and not the detailed description of the mechanisms of the various steps of the Sandmayer coupling.

[phth]

The SET pathway does not have to leave the solvent cage and copper doesnt donate an electron without binding itself to what it likes to interact with: pi bonds.  Also, weather it prefers to react with a hard or soft base is a matter of kinetic vs thermodynamic control.  HSAB is not accurate.

[pgk]

HSAB reactivity is not a matter of kinetic vs thermodynamic control, but it is a matter of effective orbitals overlapping. To detail:
Hard acid and hard bases have high electronegativity, low polarizability and a small principal atom or ion in their molecule or their ion, respectively and thus, they can successfully mix their orbitals.
Soft acids and loft bases have low electronegativity, high polarizability and a large principal atom or ion in their molecule or their ion, respectively and thus, they can successfully mix their orbitals.
Borderline acids and bases can fit their orbitals almost everywhere, depending on the relative electronegativity and  polarizability, as well as the relative size of the principal atom or ion in their molecule or their ion, respectively.
Indicative Examples:
1). Treatment of acetoacetic acid with a strong base, followed by addition of an alkyl chloride leads to the formation of the ester and not to the enol ether, regardless the reaction temperature and the addition rate of the reactants.
2). Formation of a silyl enol ether is effectuated in presence of the appropriate Lewis acid and not of a in presence of a base, regardless the reaction temperature and the addition rate of the reactants.
3). During a Grignard reaction with an aldehyde or a ketone, the Grignard reagent is not destroyed by the corresponding enol and therefore, generation of hydrogen is not observed, regardless the reaction temperature and the addition rate of the reactants.
And so on…
To be noted that recently, HSAB theory is a subject of criticism to the benefit of kinetic vs thermodynamic control. However and given that the corresponding publications are quite recent, it is rather too early for final conclusions.

[phth]

HSAB is a principle, and it is not a theory.
1) AcAcOH does so because of immense stabilization from the six membered ring not because of hardness and softness of the nucleophile.  For example: .  The stabilization depends on hydrogen bonding, dipolarity of the solvent, etc.  Quantitatively measured using NMR The opposite is observed because of reasons other than polarizability and electronegativity   HSAB is not taking into account any of these types of equilibria; it is a gas phase assumption.  Here is a gas phase reaction  



2)  I assume your talking about TiCl₄ If we change the enol or reaction to a different type of reactivity, for example phenol, the same trend is observed but with different more pronounced product ratios   Enamines are a textbook example of HSAB being wrong



3)  Grignard is radical addition to carbonyl, and radicals are unreactive to enolates.

[discodermolide]

Just to comment here. I saw/read this review a couple of years ago. It may be worth a read if you all have not already read it .
Farewell to the HSAB Treatment of Ambident Reactivity
Herbert Mayr,* Martin Breugst, and Armin R. Ofial
DOI: 10.1002/anie.201007100

[phth]

Ah, yes one of my favorites .

[pgk]

Dear phth,
I really appreciate your hard work, in order to collect and post all these documents. However, as hardly as I have tried, I cannot find anything therein that is against the HSAB theory.
1). AcAcOEt is not exactly the same as AcAcOH, where the hard base keeps the right to prefer to react with the hard carboxylic acid instead of the borderline enol acid and the borderline C-H acid; while in the case of AcAcOEt, there is competition between of the enol and the C-H borderline acids.
Always remember that the terms: acidity, basicity, electronegativity, polarizability and atoms/ions size are relative meanings.
2). The solvent effects towards enol/ketone equilibrium, as well as towards driving of parallel reactions, are well known. But remember that in addition to other interfering factors (e.g. H-bonding, polarizability changes, etc.), the strength of acids and bases significantly varies within different solvent media.
3). I am not talking about TiCl4 but about the formation of ketones silyl ethers. Anyway, in the posted reaction the tertiary chloride is leaving in Lewis acidic conditions, by Sn1 mechanism and forms a hard carbocation acid which prefers to react with the hard amine base site instead of the borderline carbanion site of the cyanide anion (Do not confuse hard adamantane carbocation acid with the phenyl carbocation, which a borderline acid, due to the aromatic conjugation).
4). HSAB theory is not applicable in Cope type rearrangement and peryciclic reactions that are perfectly explained by the Woodward-Hoffmann rules. HSAB theory is just a theory and not a principle, nor a theorem, neither a doctrine. Theories are susceptible to limitations and exceptions and have a well determined applicability range. Application of theories out of their applicability range, leads to extremities and mistakes. Your favorite publication is an assay to overcome the limitations, the exceptions and the extremities of the HSAB theory and thus, well done to be published. But, as mentioned above, it is too early for final conclusions. Besides, this a unique publication against thousands on HSABs and their proven applications in various sectors, biological sciences included.
5). Grignard reactions are nucleophilic attacks to the carbonyl and not radical reactions. The radical step is the initial incorporation of magnesium into alkyl(aryl) halide molecule. Once started the Grignard reaction, it cannot be stopped by the addition of a radical scavenger, in the second step. Besides, if you use pre-prepared Grignards (e.g. from Aldrich), you do need to add iodine crystals.
6a). By ending, please, do not be so fanatic with science but always keep a doubt, exactly as the authors of your favorite publication, did.
6b). Please also, do not be the first one who adopts a new theory, nor the last one who abandons an old theory (Except, if the new theory inventor is your class professor or your thesis supervisor).
Best Regards.

[phth]

1) the point is the metals have different hard/softness but they are statistically the same
2) maybe this is a bad example
3)  If you heat the N-cyanate will isomerize into C-cyanate because it is a less reversible reaction.  HSAB predicts that this reaction is not valid hard+soft>hard+hard!
4) It's not that the fact that cope happens it's the fact that N alkylation occurs before C alkylation leading to a major product, which HSAB predicts as unfavorable. 
5)  Well yes, but not in all cases in a more o'ferrall jenks way
Theories are true in all cases and HSAB is not which is why it is not a theory by definition.

[orgopete]

The poster wanted to know why copper was used to prepare chlorides and bromides. I'm still lost.

Re:HSAB
I'm generally unimpressed with the theory, though I think it does attempt to note some differences in atomic properties. It seems fraught with exceptions or ambiguous interpretations, as phth is pointing out. None the less, if anyone were to find HSAB theory helpful to them, then . . .

I can imagine copper could operate by a different mechanism. What I find baffling is why it should work with chlorine and bromine, but it is not used with fluoride and iodide.

[pgk]

Orgopete is right. The discussion went too far. However, it was a good chance to clarify issues and details by different points of view, that sometimes are obscurely described in texts.
Getting back to the initial question:
During heating above 5oC, the aryl diazonium salt decomposes and forms gaseous nitrogen and an aryl carbocation. Due to the aromatic conjugation, the so formed aryl carbocation is borderline acid that can react with the iodide anion which a soft base but not with fluoride, chloride and bromide anions that are hard bases. By using CuCl and CuBr as chloride and bromide sources, the coupling occurs via a radical mechanisms and thus, the desired aryl chloride and aryl bromide are easily formed. On the other hand, fluorine is the most electronegative element with the highest redox potential (> 3.0 V/eq. per L) and therefore, it cannot be oxidized by the Cu(I) mediated, aryl radical and thus, the method fails. But the aryl fluoride can be formed by using the Na[BF4] complex salt. Please, note that [BF4]- is a large complex anion with high polarizability and therefore, it behaves as a soft base that reacts with the aryl carbocation borderline acid and forms the corresponding organohemimetallic complex salt, Ar+, [BF4]-, which upon heating, it decomposes and forms gaseous boron trifluoride and the corresponding aryl fluoride:
Ar+, [BF4]-   →   ArF  +   BF3
It is obvious that the desired aryl chloride and aryl bromide, can also be prepared by using NaBCl4 and NaBBr4, respectively. But, it must be noted that the oprerationl protocol of the said method is complicated, it demands exhaustive heating and it is not free of potential danger. Therefore, the preparation of these aryl halides by using the corresponding Cu(I) salts, is largely preferred.
PS: Any reasonable analysis of all above that is based on the kinetics/thermodynamics competition of the Sandmeyer reaction, is fully welcome.