4-Substituted 2-hydroxyacetophenones

An extensive kinetic study of the iodination of substituted hydroxyacetophenones by iodine monochloride has been carried out in aqueous acetic acid. ... 

Transition-metal catalysed enantio-selective a-heterofunctionalization of carbonyl compounds has been reviewed. The kinetics and mechanism of iodination of substituted hydroxyacetophenones by iodine monochloride (ICl) in acetic acid/water... 

In this handbook set, the reader will find four independent parts which successively cover the topics of monoaroyl and polyaroylphenols in Volume 1, hydroxyacetophenones in Volume 2, substituted hydroxyacetophenones in Volume 3 and hydroxypropiophenones, hydroxyisobutyrophenones and hydroxypivalophenones in Volume 4. 

The ester and catalj st are usually employed in equimoleciilar amounts. With R =CjHs (phenyl propionate), the products are o- and p-propiophenol with R = CH3 (phenyl acetate), o- and p-hydroxyacetophenone are formed. The nature of the product is influenced by the structure of the ester, by the temperature, the solvent and the amount of aluminium chloride used generally, low reaction temperatures favour the formation of p-hydroxy ketones. It is usually possible to separate the two hydroxy ketones by fractional distillation under diminished pressure through an efficient fractionating column or by steam distillation the ortho compounds, being chelated, are more volatile in steam It may be mentioned that Clemmensen reduction (compare Section IV,6) of the hj droxy ketones affords an excellent route to the substituted phenols. 

The Knoevenagel reaction between o-hydroxyaryl aldehydes and ketones and substituted acetonitriles affords high yields of 3-substituted coumarins in aqueous alkaline media <96H(43)1257>, whilst 4-hydroxycoumarins have been elaborated to pyrano [3,2-c]benzopyran-5-ones by reaction with aromatic aldehydes and malononitiile <96P148>. The imine (10) resulting from the complex reaction of o-hydroxyacetophenone with malononitrile undergoes a 1,5-tautomeric shift in solution <96JCS(P1)1067>. 

Investigation of Chlorine Substitution Effects in the Claisen-Schmidt Condensation of 2 -Hydroxyacetophenone with Chlorobenzaldehydes Over MgO... 

The Claisen-Schmidt condensation of 2 -hydroxyacetophenone and different chlorinated benzaldehydes over MgO has been investigated through kinetic and FTIR spectroscopic studies. The results indicate that the position of the chlorine atom on the aromatic ring of the benzaldehyde substantially affects the rate of this reaction. In particular, the rate increases in the following order p-chlorobenzaldehyde < m-chlorobenzaldehyde < o-chlorobenzaldehyde. The difference between the meta and para-substituted benzaldehyde can be attributed to electronic effects due to the difference in the Hammett constants for these two positions. Steric effects were found to be responsible for the higher rate observed with the o-chlorobenzaldehyde. 

Syntheses of 2- and 3-substituted chromones normally start from 2-hydroxyphenyl ketones. In the first of two examples, a route to flavone is shown in Scheme 5,10 using 2-hydroxyacetophenone (2-hydrox-yphenylethanone) and benzoyl chloride as starting materials. Initially, the phenolic group of the acetophenone is O-acylated by benzoyl chloride, using pyridine as a base (a Schotten-Baumann-type reaction). 

Both phenylhydrazones and imines derived from 5-halogeno-2-hydroxyacetophenones 510 were cyclized to the corresponding 4-methylene-substituted l,3-benzoxazin-2-ones 194 and 511 on treatment with 0.5 or O.bequiv of triphosgene under mild conditions (Scheme 96) <2003X8163, 2004SC71>. In the similar reactions of arylhydra-zones of 2-hydroxyacetophenones with 1 equiv of triphosgene, spiro-l,3-benzoxazine dimers were formed <2002JCM473>. 

Oxovanadium(IV) complexes with (97) and (98) derived from alkyl aminoalcohols and Hsal or o-hydroxyacetophenone (and substituted derivatives), respectively, have been prepared as well as VOz+ complexes with (99) derived from 2-hydrazinoethanol and Hsal and substituted Hsal. Most of these and some properties are summarized in Table 42. Generally the complexes were prepared by adding an alcoholic solution of the SB, either previously obtained as a solid or prepared in situ, to alcoholic vanadyl acetate. The mixture is normally refluxed for several hours and the precipitates are collected by filtration as they are not soluble they are not recrystallized. 

Several older syntheses are based on o-hydroxyacetophenones but these routes generally offer little or no advantage over other methods. The Reformatsky reaction has been used to prepare 3- and 3,4-substituted coumarins (44JIC109) and the Kostanecki-Robinson reaction may yield coumarins instead of or as well as the chromone (see Section 2.24.3.4.1 for further discussion). 

Not unexpectedly, a substituent on the acetyl group of the 2-hydroxyacetophenone has an effect on the condensation, though successful preparations of 3-substituted chromones have been achieved. A neat alternative approach to such chromones involves alkylation of the intermediate diketone and subsequent cyclization (34JCS1311). 

The presence of a substituent on the original methyl group of the hydroxyacetophenone prevents formation of the labile 3-acylchromone but otherwise has little effect provided the substituent is not solvolyzed. A number of 3-substituted chromones have been obtained in this manner (55JOC38). 

Hydroxyacetophenone reacts with DMF under Vilsmeier conditions to yield chromone-3-carbaldehyde (72LA(765)8). The reaction appears to be generally applicable, various substituents being acceptable in the aromatic ring (74T3553). Furthermore, acetylhydroxy-naphthalenes yield the corresponding benzochromones, and the pyranochromone (452) is formed from the appropriately substituted coumarin. 

The use of o-hydroxyacetophenone in place of salicylaldehyde leads to the formation of 4-substituted benzopyrylium salts. 

Benzoxazoles.1 Benzoxazoles (2) are obtained in generally good yield by Beckmann rearrangement of the oxime of 2 -hydroxyacetophenones (1) using POCl3-DMA in CH3CN at 30° (equation I). The method is applicable to synthesis of hydroxy-substituted benzoxazoles, which are usually difficult to prepare. 

Triazolopyrimidines fused with the benzopyrane ring 419 (usually as mixtures of diastereomers) can be obtained by cyclization of 5-(2-hydroxyaryl)-substituted dihydroazolopyrimidines 417, with aldehydes 418, or by direct condensation of 3-amino-1,2,4-triazole 147 with ort/zo-hydroxyacetophenone 421 and 2 mole of the corresponding aldehyde [409, 410] (Scheme 3.133). In the latter case, the... 

Aldol and related condensation reactions such as Knoevenagel and Claisen-Schmidt condensations are also widely used in the fine chemicals and specialty chemicals, e.g. flavors and fragrances, industries. Activated hydrotalcites have been employed as solid bases in many of these syntheses. Pertinent examples include the aldol condensation of acetone and citral [107, 108], the first step in the synthesis of ionones, and the Claisen-Schmidt condensation of substituted 2-hydroxyacetophenones with substituted benzaldehydes [109], the synthetic... 

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