Fries rearrangement

The Fries rearrangement (or Fries rearrangement ) is a name reaction in organic chemistry. The reaction is named after its discoverer, the German chemist Karl Fries (1875-1962) named. The Fries rearrangement here describes the electrophilic rearrangement of aryl esters (eg, phenyl ) under Lewis acid catalysis to give the corresponding aryl ketone.

Mechanism

Despite considerable efforts, no conclusive statements could still be secured to the mechanism. Thus, both indications for intra-and intermolecular processes were found in cross experiments. The end of the reaction both the solvent and the substrate -dependent. Generally, however, the below mechanism is accepted as best-ever explanation. In a first step accesses the Lewis acid (in this case, aluminum chloride, AlCl3 ) to the carbonyl oxygen of the acyl group (1). This is stronger than the phenolic oxygen Negating and thus preferred destination. Characterized the bonding of the acyl group is polarized to the phenolic oxygen. Then, the aluminum migrates to the phenolic oxygen chloride (3). Here, a acylium cation 5 is released by displacement of the bonding electrons.

This acylium cation 5 then reacts with electrophilic aromatic substitution with the classic aromatics is 4 possible an attack in the ortho or para position. The orientation of the substitution is temperature dependent. At low temperature, the product is preferably the ortho- para- product at a high temperature is formed. In order to produce the aromatic state again, after electrophilic attack of a proton and obtain the ketone 7 (ortho- substitution) or 10 ( para substitution ). The resulting ketone remains bound as the anion to the aluminum. The aluminum compound is then hydrolyzed by addition of water and the desired hydroxy ketone 8 (ortho- substitution) and 11 (para- substitution) is obtained.

Ortho- substitution:

Para- substitution:

Photo- Fries rearrangement

In addition to the above-described reaction of phenyl esters, there is a designated as a photo-Fries rearrangement variant, which runs via a free radical mechanism. They can also be used in the presence deaktivierender groups on the aromatic, but is due to the hitherto used generally poor yields in the laboratory. If the para position on the phenyl by a substituent (e.g. a methyl group) is blocked, caused only ortho -hydroxy ketones. The phenyl is not substituted in the para position, mixtures of ortho-and para -hydroxy ketones. The first step of the mechanism describes the formation of an acyl radical 13 and a Aryloxiradikals 12, which is characterized by its mesomeric stabilization.

The resonance structures indicate in this case that the resulting acyl radical 13 can bind either in the ortho or para to the Aryloxiradikals 12. After the rearrangement of a proton then creates the corresponding hydroxy ketone 8 and 11

Ortho- shift

Para- shift

Importance

Since the reaction of phenol with acyl halides under the conditions of Friedel-Crafts acylation of phenyl esters, but does not provide the desired Hydroxyarylketone, is the reaction of large industrial importance for the synthesis of Hydroxyarylketone as important starting materials for the synthesis of various pharmaceutical products (for example, paracetamol, or salbutamol ) are used. Instead of the aluminum chloride may be used in some cases, other Lewis acid ( boron trifluoride, Bismuttriflat etc.) or strong protic acids ( hydrofluoric acid or methanesulfonic acid ). In order to avoid the consumption of these corrosive and environmental concern catalysts, the use of solid catalysts is studied intensively.

Confines

In all cases, only those esters are used of which the acyl component under the harsh conditions is stable. Is the aromatic acyl component or highly substituted, due to severe steric strain, the yield drops sharply. Deactivating ( meta-directing ) groups on the aromatic let yields drop drastically, as is expected for a Friedel -Crafts reaction.