Development of alternative technology for the production of meta-substituted phenolic compounds

[摘要] English: Both m-cresol and resorcinol are important industrial starting materials in the productionof many phenolic products.In a process similar to the one for the production of phenol, cresols are produced byreaction of toluene with propylene to give mixtures of o-, m- and p-isopropyltoluene.The corresponding cresols are subsequently obtained together with acetone via thehydroperoxides by air oxidation. Due to their close boiling points, m- and p-cresol arenot separable by distillation and has to be obtained from these mixtures by elaborateadduct crystallisation, derivatization or chromatographic procedures, which results inpure synthetic m-cresol to be a very expensive commodity. Since it is known that mcresolcan be produced selectively from o- or p-toluic acid, which is readily availablefrom the corresponding xylene, by application of Keading's Dow Phenol process, it wasdecided to investigate this methodology as an alternative for the synthesis of pure mcresol.In order to be in a position to optimise this process, it was decided to investigatethe mechanism of the reaction through the use of X-ray diffractometry,thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), infraredspectrometry (IR) and MALDI-TOF mass spectrometry.The starting point in the copper catalysed process for transforming o-toluic acid into mcresol,has been established by X-ray diffractometry to be the formation of tetrakis(μ2-2-methylbenzoato)bis(2-methylbenzoic acid)copper(II), with the typical paddlewheelstructure of Cu(II) carboxylates, when o-toluic acid was reacted with basiccopper(II)carbonate and magnesium oxide in refluxing toluene. Apart from the expectedfour o-toluic acid entities forming the paddlewheel structure, the crystal structure alsoindicated another toluic acid molecule to be attached to each copper atom through thecarbonyl of the carboxylic acid moiety. Extension of the X-ray crystallographicinvestigation to the copper salts of p-toluic acid, m-toluic acid, p-ethylbenzoic acid, and2,6-dimethylbenzoic acid indicted all of these compounds, except the copper (II) salt ofp-toluic acid, to have structures similar to that of tetrakis(μ2-2-methylbenzoato)bis(2-methylbenzoic acid)copper(II). While the structure of tetrakis(μ2-4-methylbenzoato)bis(4-methylbenzoic acid)copper(II) basically also showed the paddlewheelconfiguration, the extra two toluic acid molecules attached to the copper atoms in the allof the other cases were absent in the structure of this compound. In this instance,interactions between an oxygen atom of one molecule and the copper of an adjacentmolecule leading to an infinite 'polymer type chain along the a-axis of the crystal, wasobserved.Evidence gathered from DSC, TGA, and MALDI-TOF MS investigations of thetransformation of tetrakis(μ2-2-methylbenzoato)bis(2-methylbenzoic acid)copper(II) intothe product, suggested that this copper benzoate rearranges and cleaves into o-toluic acidand copper(I) 2-methyl-6-{[(2-methylphenyl)-carbonyl]oxy}benzoate at 164 °C.Decarboxylation of the latter at 249.5 °C gave o-toluic acid and 3-methylphenyl 2-methylbenzoate, which is hydrolysed into o-toluic acid and the desired product, m-cresol.In contrast to the copper salt of o-toluic acid, which showed clear temperature differencesfor the different steps in the reaction process, the salt of p-toluic acid displayed onecontinuous decomposition between 160 and 260 oC, thus rendering the identification ofreaction intermediates at specific temperatures more or less impossible.In a process similar to that of cresols, resorcinol is commercially produced by selectiveformation of m-diisopropylbenzene followed by oxidative cleavage of thedihydroperoxide which is obtained through aerial oxidation of the diisopropylbenzene.While this process is used globally, it is hampered by large recycle streams arising frompoor o/p selectivity during the alkylation of benzene as well as the limitation of lowconversion (20%) in the oxidation step due to the explosivity of the hydroperoxideintermediate. Since it has been demonstrated that the Diels-Alder reaction could beapplied to the synthesis of p-cresol from isoprene and vinyl acetate, application of thismethodology to the synthesis of resorcinol, was subsequently investigated.Danishefsky's diene (trans-1-methoxy-3-trimethylsilyloxy-1,3-butadiene), with theappropriate functional groups already trapped in the required enolic form, was selected asmodel substrate for the preliminary experiments with model dienophiles, methyl vinylketone and butyl acrylate and the novel cis- and trans-products, 4-acetyl-3-methoxycyclohexanone and butyl 2-methoxy-4-oxocyclo-hexanecarboxylate, obtained,albeit in low yields (7.49 and 6.59 % and 7.53 and 9.66 % respectively). When thereaction was extended to the more relevant methyl propiolate as dienophile, no directDiels-Alder products could, however, be isolated and only methyl 4-hydroxybenzoate and methyl 4-{[(1E)-3-methoxy-3-oxoprop-1-en-1-yl]oxy}benzoate were isolated fromthe reaction mixture in 5.51 and 5.74 % yields respectively. The formation of the phydroxybenzoateis explicable in terms of methanol elimination from the primary Diels-Alder product, while it is clear that the second product originates from conjugate additionof the formed hydroxybenzoate to methyl propiolate. While seemingly negative, the lastDiels-Alder reaction, however, showed that the envisaged methodology could in principlebe used for the preparation of resorcinol, but that care would have to be taken in order toavoid unwanted methanol release. If Chan's diene [1,3-bis-(trimethylsilyloxy)-1-methoxy-1,3-butadiene] or an equivalent to it, could be used in a Diels-Alder reactionwith an acrylate, the tendency towards methanol elimination might, however, beadvantageous as it might lead to the mono-silylated resorcinol derivative in a single step.The viability of this Diels-Alder strategy towards the synthesis of resorcinol will formpart of a future investigation.While negative from the point view of methodology for the synthesis of resorcinol, theDiels-Alder reaction between methyl propiolate and Danishefsky's diene represents anew catalytic process for the preparation of methyl 4-hydroxybenzoate. This compound iswidely used as a preservative in food, cosmetics and pharmaceuticals, while its free acidform (p-hydroxybenzoic acid), which is produced by Kolbe-Schmidt carboxylation ofpotassium phenolate with carbon dioxide, finds application in the liquid crystal industry.

[发布机构] University of the Free State