Oxidation acetophenone synthesis

Figure 9.1 Acetophenone synthesis by stoichiometric and catalytic oxidation.

Sales demand for acetophenone is largely satisfied through distikative by-product recovery from residues produced in the Hock process for phenol (qv) manufacture. Acetophenone is produced in the Hock process by decomposition of cumene hydroperoxide. A more selective synthesis of acetophenone, by cleavage of cumene hydroperoxide over a cupric catalyst, has been patented (341). Acetophenone can also be produced by oxidizing the methylphenylcarbinol intermediate which is formed in styrene (qv) production processes using ethylbenzene oxidation, such as the ARCO and Halcon process and older technologies (342,343). 

In a significant addition to the synthesis of 1,2,4-oxadiazoles (Scheme 41), Itoh et al. discovered that the treatment of nitriles with iron(lll) nitrate in the presence of acetone or acetophenone gives the 3-acetyl- or 3-benzoyl-l,2,4-oxadiazoles 260, proposing that enolization and nitration gives an a-nitroketone, which then undergoes an acid-catalyzed dehydration to give the nitrile oxides 259 <2005S1935>. 

Wacker oxidation of styrene has also been performed in [bmim][BF4] and [bmim][PF6], at 60 °C with H2O2 and PdCF as a catalyst [19]. This system gave yields of acetophenone as high as 92 % after 3 h. Hydrogen peroxide may also be used under phase transfer conditions for alkene bond cleavage, to produce adipic acid (an intermediate in the synthesis of nylon-6) from cyclohexene (Scheme 9.9). 

Figure 9.1 compares the synthesis of acetophenone by classic oxidation of 1-phenylethanol with stoichiometric amounts of chromium oxide and sulphuric acid, with an atom efficiency of 42%, with the heterogeneous catalytic oxidation with O2, with an atom efficiency of 87%, and with water as the only by-product. This is especially important if we consider the environmental unfriendliness of chromium salts the potential environmental impact of reactions can be expressed by the environmental quotient (EQ), where E is the E-factor (kg waste/kg product) and Q is the environmental unfriendliness quotient of the waste. If Q is... 

The use of dinitrogen pentoxide in the Ponzio reaction for the oxidation-iutration of oximes to em-dinitro groups has been reported by Russian chemists. Millar and co-workers extensively investigated these reactions and reported the synthesis of 2,4,5,7,9,9-hexanitrofluorene (2), a thermally stable explosive with an oxygen balance better than TNT. Other energetic materials containing gem-dinitro functionality were synthesized from the oximes of acetophenone, 4-nitroacetophenone, a-nitroacetophenone and 2-hydroxyacetophenone. 

To complete the section on the synthesis of 4,4 -bipyridines, we summarize the methods reported for the preparation of some substituted 4,4 -bi-pyridines and 4,4 -bipyridinones. These methods are closely analogous to syntheses already discussed for some of the isomeric bipyridines. Thus the Hantzsch reaction using pyridine-4-aldehyde, ethyl acetoacetate, and ammonia gives 3,5-di(ethoxycarbonyl)-1,4-dihydro-2,6-dimethyl-4,4 -bipyridine, which after oxidation, followed by hydrolysis and decarboxylation, afforded 2,6-dimethyl-4,4 -bipyridine. Several related condensations have been reported. Similarly, pyridine-4-aldehyde and excess acetophenone gave l,5-diphenyl-3-(4-pyridyl)pentane-l,5-dione, which with ammonium acetate afforded 2,6-diphenyl-4,4 -bipyridine. Alternatively, 1-phenyl-3-(4-pyridyl)prop-2-enone, A-phenacylpyridinium bromide, and ammonium acetate gave the same diphenyl-4,4 -bipyridine, and extensions of this synthesis have been discribed. Condensation of pyridine-4-aldehyde with malononitrile in the presence of an alcohol and alkaline catalyst produced compounds such as whereas condensations of... 

Formerly, benzoic acid was produced by the decarboxylation of phthalic anhydride. Oxidation of acetophenon, benzyl bromide, and toluene with sulfur and water has been described in the literature, but are not commercially feasible routes of synthesis. Carboxylation of benzene with carbon dioxide is not practical due to the instability of benzoic acid at the required reaction conditions [8]. 

The reaction of o-nitrobenzaldehydes with some benzene derivatives in the presence of strong acid (H2S04, PPA) is a classical synthesis of acridinol N-oxides (373) (37BSF240) The synthesis works for benzyl alcohol, benzene, toluene and halobenzenes, but not for benzoic acid, benzonitrile, dimethylaniline, or nitrobenzene. Isoquinoline N-oxides (374) have been obtained from o-bromobenzaldoxime or the acetophenone derivative, and active methylene compounds with copper bromide and sodium hydride (77S760). The azobenzene cobalt tricarbonyl (375) reacts with hexafluorobut-2-yne to give a quinol-2-one (72CC1228), and the 3,4,5-tricyanopyridine (376) is formed when tetracyanoethylene reacts with an enaminonitrile (80S471). 

One research group has exploited the concept of polymer site-isolation in a multistep/one-chamber solution-phase synthesis in which all the reagents, catalysts, and downstream reactants required for a multistep synthesis were combined in one reaction chamber. For instance, a one-chamber/three-step synthesis of substituted acetophenones has been reported (Scheme 10).84 An a-phenethyl alcohol was introduced into a reaction chamber containing the polymer-supported reagents and reactants necessary to accomplish oxidation by polymer-supported pyridinium dichromate 60 bromination by the A-26 perbromide resin 61 and nucleophilic displacement by the A-26 phenoxide resin 62. Filtration afforded the... 

The synthesis of rofecoxib can be achieved by several different routes (Drugs Fut., 1998). A highly efficient synthesis for rofecoxib was recently described (Therien et al., 2001). As illustrated in Scheme 79, acetophenon (i) is prepared according to the literature, by Friedel-Crafts acylation with thioanisole. Oxidation with MMPP (magnesium monoperoxyphthalate hexahydrate) affords the sulfone (ii), which is reacted with bromine in chloroform in the presence of a trace amount of AICI3, to give (iii). Bromoketone (iii) is than coupled and cyclized in a second step, one-pot procedure with phenylacetic acid. Firstly, the mixture of bromoacetophenone (iii) and phenylacetic acid in acetonitrile is treated with... 

The synthesis of oxygen-heterocycles by intermolecular reactions of a-TK with nucleophiles has received only limited attention. However, a-tosyloxy derivatives of several acetophenones have been prepared by brief exposure of neat HTIB/ketone mixtures to microwave (MW) radiation, and employed on mineral oxide surfaces for microwave-assisted syntheses of thiazoles and 2-aroylbenzofurans 40 (Scheme 11) (98JCS(P1)4093, 99JHC1565). 

C.S. Cooper and co-workers synthesized several quinolones containing five- and six-membered heterocyclic substituents at the 7-position and tested their antibacterial activities. The 1,4-diketone substrate was prepared via the oxidative coupling of isopropenyl acetate and an acetophenone derivative. The Paai-Knorr furan synthesis was conducted in the presence of p-TsOH. 

A synthesis of substituted phenanthrenes has been reported using the bicyclooctadienes (61) as starting material. The process makes use of the nucleofugal group on C-8 and follows the path outlined in Scheme 3. This involves a di-rr-methane bridging process followed by the collapse of the intermediate biradical (62). Normal di-Ti-methane behaviour is reported in the acetophenone-sensitized irradiation of the isoquinolinone derivative (63a). This yields the two products (64) and (65) as a 3 1 mixture in a total yield of 75%. An N-oxide derivative gave a brown polymer with little evidence for the formation of di-n-methane products. The influence of ring substituents was also studied for the derivatives (63b, d) and the results of this are shown in Scheme 4. The authors conclude that the cyclization process is under LUMO control. Irradiation of the dihydropyridine (66) affords the oxidised pyridine (67) as the major product. A minor product (68) is also formed by a di-ir- methane process. ... 

Nucleoside Pyrophosphates. - The synthesis of 8-aryl-3-P-o-ribofuranosylimiazo[2,l-i]purine 5 -phosphates (122) from AMP or ATP has been described. To access these fluorescent nucleotide derivatives, a combination of Kornblum oxidation reaction and imidazole formation was employed. For this conversion, the appropriate adenosine phosphate, present in its free acid form, was treated with p-nitro-acetophenone in DMSO in the presence of DBU. Treatment of a 5-(chloroethyl)-4-(triazole-l-yl)pyrimidine-nucleoside with benzylhydrazine offered the 6,6-bicyclic pyrimido-pyradazin-7-one, the precursor to (123). This triphosphate was used as a substrate for DNA polymerases. ... 

The most useful procedure utilises a 1,4-keto-ester giving a dihydro-pyridazinone, which can be easily dehydrogenated to the fully aromatic heterocycle, often by C-bromination then dehydrobromination alternatively, simple air oxidation can often suffice. 6-Aryl-pyridazin-3-ones have been produced by this route in a number of ways using an a-amino nitrile as a masked ketone in the four-carbon component, or by reaction of an acetophenone with glyoxylic acid and then hydrazine. Friedel-Crafts acylation using succinic anhydride is an alternative route to 1,4-keto-acids, reaction with hydrazine giving 6-aryl-pyridazinones. Alkylation of an enamine with a phenacyl bromide prodnces 1-aryl-l,4-diketones, allowing synthesis of 3-aryl-pyridazines. ... 

The 1,2,3-selenadiazoles without fused rings were unknown until 1969 when Lalezari et a/.50,51 described the synthesis of 4-aryl-l,2,3-selenadiazoles (106) by the selenium dioxide oxidative ring closure of the semicarbazones of acetophenones. The mechanism proposed for this reaction is shown in Scheme 12. The mechanism was verified by the isolation of diphenylurea from the oxidation of the 4-phenylsemicarbazone derivative. The alternative mechanism proposed by Meier and Voigt does not account for this finding.52... 

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