Aromatic hydroxyketone production

It is my great pleasure to write a foreword for Dr. R. Martin s handbook on Fries rearrangement and their aromatic hydroxyketones products. The present work is the result of numerous years of experience in compiling and editing data. 

The production of aromatic hydroxyketones can also be performed by the Fries rearrangement in this case, the mode of para-acylation is probably different from that of ortho-acylation. Indeed, the ortho-isomer is a primary product, whereas the para-isomer seems to be a secondary product. Of course, other methods for... 

Of the other derivatives of aromatic hydroxyketones used as photostabilizers, the reaction products of aliphatic or arylaliphatic mono-and dinitriles with phenols are indicated [23, 52-54] ... 

Once generated, the nucleophilic carbanion (I) attacks a second molecule of the aromatic aldehyde to yield a substituted C5 ohydrin. This species can then be stabilized by loss of cyanide ion to form the a-hydroxyketone product. 

P-Hydroxyketones are also subject to fragmentation. Lewis acids promote fragmentation of mixed aldol products derived from aromatic aldehydes.100... 

TS-1 zeolites have been used in the presence of H2O2 to perform the BV reaction on cyclic and aromatic ketones . Cyclohexanone and acetophenone can be oxidized at 80 °C with selectivities lower that 60%, due to the formation of a-hydroxyketones and other undesired products. The observed modest results seem to be associated with the poor selectivity of the active Ti-peroxo species. In this respect, Corma and coworkers developed new Sn-based heterogeneous catalysts able to selectively activate the ketone instead of 11202 . Cyclic ketones are transformed into the corresponding lactones and unsaturated cyclic ketones like 110 are oxidized to unsaturated lactones in very high chemoselectivitjf , unusual for other oxidizing systems (equation 75). As expected, the authors failed to detect the presence of metal-peroxo derivatives in their systems . ... 

Unlike formamidine, acetamidine and benzamidine react with both aromatic and aliphatic a-hydroxyketones to give imidazoles exclusively. It has been suggested that aryl groups favour the enolic form (2) of the tautomeric mixture, resulting in the formation of oxazoles as major products. Aliphatic groups favour the keto form (1), from which imidazoles are derived. That amidines more complex than formamidine favour imidazole formation may be a consequence of steric hindrance to reaction of the enolic hydroxy groups with the amidine carbon in (2). The general reaction has been used to prepare such compounds as 4,5-dipropyl imidazole (25% yield from tris(formylamino)-methane and 5-hydroxyoctan-4-one), and a variety of 2-imidazolones and 2-aminoimidazoles [8]. The fact that oxazoles can be converted into imidazoles with some ease extends the applicability of this reaction. 

Recently, the benzoin condensation of aromatic or heteroaromatic aldehydes (in the absence of VOCs and bases) catalysed by NHCs, obtained by cathodic reduction of RTILs, has been reported. a-Hydroxyketones have been isolated in good to elevated yields, in short reaction time. No a-hydroxyketones have been obtained from linear or short-branched aldehydes instead aldol products and carbene-aldehyde adducts have been isolated in elevated yields (Scheme 16.22) [150,151]. 

A catalyzed alcohol reaction (b) on lignin takes place at -hydroxyketones, carbonyl, and carboxyl groups. The reactions give different products and are shown in equation 3. Since alcohol/acid alkylation does not alkylate the aromatic hydroxyl groups (108), alkyllignins fiom these reactions have sharply different solubility... 

The aldol reaction of cyclic ketones and acetone with aromatic aldehydes were carried out in combination with triflic acid in water at 25°C [250]. Other chiral primary-tertiary diamine catalyst such as compound 167 (20 mol%) was used in combination with solid polyoxometalate acid support (6.67% mol) in the aldol reaction between dihydroxyacetone (149a) and aromatic aldehydes in NMP as solvent at 25°C to afford mainly iyn-aldol products in good yields (59-97%) and high diastereo- and enantioselectivities (78-99% de, 84-99% ee). The combination of catalyst 167 with triflic acid was used in the reaction of acyclic ketones and a-hydroxyketones 8 with aromatic aldehydes also with good results [251]. Simple chiral diamine 168 (10 mol%) in the presence of Iriflic acid (20 mol%) was applied as catalyst in the reaction between acetone and cyclohexanone with aromatic aldehydes in water at 25°C, giving aldol adducts 4 in low yields (15-58%) and moderate diastereo- and enantioselectivities (50-98% de, 45-93% ee) [252]. 

A method for the preparation of higher sugars with an aromatic branch has been developed which involves a Michael addition - aldol condensation sequence and uses carbohydrate silylenol ethers, e.g. compound (42), as starting materials. As is demonstrated in Scheme 9, the Michael addition product was obtained as the stable silylenol ether (43). On desilylation, aldol condensation took place to give the cyclic hydroxyketone (44) which aromatised under acetylation conditions. The introduction of an aromatic branch by Diels-Alder cyclisation of a carbohydrate diene is referred to in Chapter 19. 

Platonova and coworkers " synthesized materials by the reaction of zirconocene dichloride with aromatic polymers bearing alpha-diketones and alpha-hydroxyl ketone moieties. The product was formed through reaction with the hydroxyketone functional group. 

Ring Closure Reactions Heravi et al. studied the synthesis of 2,4,5-trisubstituted imidazoles through three-components coupling of l,2-diketone/l,2-hydroxyketone, aromatic aldehydes, and ammonium acetate using MCM-41 as catalyst under solvent-free conditions [96]. MCM-41 efficiently catalyzes the reaction affording the desired product in good yields in a relatively short time (Scheme 22). 

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