Cumene hydroperoxide rearrangement

Bisphenol A is manufactured by a reaction between phenol and acetone, the two products from the cumene hydroperoxide rearrangement. The temperature of the reaction is maintained at 50 °C for about 8-12 hr. A sluny... 

The most common current method of phenol production is from the cumene hydroperoxide rearrangement process. In this process, benzene reacts with propylene to produce cumene. Cumene is oxidized to cumene hydroperoxide. When cumene hydroperoxide is treated with dilute sulfuric acid, it rearranges and splits into phenol and acetone. Because the reactants are inexpensive and the process is simple, the acidic oxidation of cumene is used to produce more than 95% of the worlds supply of phenol. 

By contrast with the conditions for aldehydes, ketones have been oxidised to phenols by methodology essentially that of the cumene-hydroperoxide rearrangement. In the naphthalenic series, treatment of the derived t-alcohol shown with excess 90% hydrogen peroxide followed by stirring of the mixture with a little 4-toluenesulphonic acid for 6 hours at 22 C gave the phenolic product, 2-hydroxy-3-methoxy-5,6,7,8-tetrahydronaphthalene in 85% yield (ref.45). 

One of the mdustnal processes for the preparation of phenol discussed in Section 24 6 includes an acid catalyzed rearrangement of cumene hydroperoxide as a key step This reaction proceeds by way of an intermediate hemiacetal... 

Mechanism of the formation of phenol by acid-catalyzed rearrangement of cumene hydroperoxide. 

Here, cumene hydroperoxide is rearranged to provide phenol and acetone via acid cleavage. 

Rearrangements of Hydroperoxides Investigated in Micro Reactors Organic synthesis 82 [OS 82] Rearrangement of cumene hydroperoxide... 

The major manufacturing process for making phenol was discussed in Chapter 10, Section 4, since it is the co-product with acetone from the acid-catalyzed rearrangement of cumene hydroperoxide. The student should review this process. It accounts for 95% of the total phenol production and has dominated phenol chemistry since the early 1950s. But a few other syntheses deserve some mention. 

In oxidation studies it has usually been assumed that thermal decomposition of alkyl hydroperoxides leads to the formation of alcohols. However, carbonyl-forming eliminations of hydroperoxides, usually under the influence of base, are well known. Of more interest, nucleophlic rearrangements, generally acid-catalyzed, have been shown to produce a mixture of carbonyl and alcohol products by fission of the molecule (6). For l-butene-3-hydroperoxide it might have been expected that a rearrangement (Reaction 1) similar to that which occurs with cumene hydroperoxide could produce two molecules of acetaldehyde. 

Kennerly and Patterson (13) studied the effect of several organic sulfur compounds, including thiols, sulfides, a disulfide, sulfonic acids, and a zinc dialkyl dithiophosphate, on the decomposition rate of cumene hydroperoxide in white mineral oil at 150 °C. In each case they found phenol as the major product. They suggested that the most attractive mechanism by which to explain these results involves ionic rearrangement catalyzed by acids or other electrophilic reagents (10) as... 

No readily acceptable mechanism has been advanced in reasonable detail to account for the decomposition of hydroperoxides by metal dialkyl dithiophosphates. Our limited results on the antioxidant efficiency of these compounds indicate that the metal plays an important role in the mechanism. So far it seems, at least for the catalytic decpmposition of cumene hydroperoxide on which practically all the work has been done, that the mechanism involves electrophilic attack and rearrangement as shown in Scheme 4. This requires, as commonly proposed, that the dithiophosphate is first converted to an active form. It does seem possible, on the other hand, that the original dithiophosphate could catalyze peroxide decomposition since nucleophilic attack could, in principle, lead to the same chain-carrying intermediate as in Scheme 4 thus,... 

Probtem 19.7 Give a mechanism for the acid-catalyzed rearrangement of cumene hydroperoxide involving an intermediate with an electron-deficient O (like R ). ... 

Another BMS example, shown in Scheme 11.14, uses a cumene peroxide rearrangement to prepare 6-hydroxy-5-methyl-3H-pyrrolo[2,l-f [l,2,4]triazin-4-one, an intermediate for protein kinase inhibitors (brivanib). The terhary alcohol is converted to the hydroperoxide in situ with H2O2 and reacted with aqueous meth-anesulfonic acid as a catalyst to cause rearrangement [31]. 

The oxidation is carried out in the liquid phase, at relatively low temperature (90-120°C), pressure (5-7 atm), and conversion rate (20-40%) to achieve high selectivity. Cumene hydroperoxide is concentrated (70-85%) and then further converted. This second step includes an acid-catalyzed rearrangement and cleavage977 yielding phenol and acetone ... 

Cumene oxidized relatively slowly, at about 1/13 the rate of p-xylene. This was not caused by the formation of phenol, as might be expected by an acid-catalyzed rearrangement of cumene hydroperoxide. No phenol or product clearly derived from phenol, as by radical attack or by oxidation to a quinone, was detected at any time in the reaction mixture. The two major products were a-methylstyrene and 2-phenylpropylene oxide their concentrations increased with time. The group at Shell also observed the formation of a-methylstyrene and 2-phenylpropylene oxide among the products of cumene oxidation in butyric acid at 140°C. with cobalt and manganese catalysts (30). 

Similarly, the cumyloxenium ion 320 is involved in the acid-catalyzed cleavage rearrangement reaction of cumene hydroperoxide to phenol and acetone [Eq. (4.184)]. 

The dissolved sodium carbonate helps to maintain the system to near neutral pH to avoid premature rearrangement of the hydroperoxide. The partially converted cumene from the first stage is carefully concentrated to about 80% cumene hydroperoxide before proceeding to the rearrangement step. 

Dilute sulfuric acid at 70-80°C is used to rearrange the cumene hydroperoxide to phenol and acetone, for which the stoichiometry is represented by Eq. 19.50. 

Several approaches are currently used to produce cyclohexanone. Two autoxidative processes which are relevant to this presentation will be discussed here. First, we will discuss the AlliedSignal process. In this approach, cumene (isopropylbenzene) is reacted with air at 105 at 5 psig to form cumene hydroperoxide. The conversion is slow but the selectivity is high approaching 100%. The hydroperoxide when heated at 77 with sulfuric acid, rearranges to form equimolar amounts of phenol and acetone. Phenol is then reduced at 155 by hydrogen at 80 - 220 psig in the presence of Pd on carbon to form cyclohexanone. About 10% of cyclohexanol is also formed. 

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