Development of alternative technology for the production of meta-substituted phenolic compounds
| dc.contributor.advisor | Bezuidenhoudt, B. C. B. | |
| dc.contributor.author | Sunil, Abraham C. | |
| dc.date.accessioned | 2016-06-08T18:45:18Z | |
| dc.date.available | 2016-06-08T18:45:18Z | |
| dc.date.issued | 2009-11 | |
| dc.description.abstract | English: Both m-cresol and resorcinol are important industrial starting materials in the production of many phenolic products. In a process similar to the one for the production of phenol, cresols are produced by reaction of toluene with propylene to give mixtures of o-, m- and p-isopropyltoluene. The corresponding cresols are subsequently obtained together with acetone via the hydroperoxides by air oxidation. Due to their close boiling points, m- and p-cresol are not separable by distillation and has to be obtained from these mixtures by elaborate adduct crystallisation, derivatization or chromatographic procedures, which results in pure synthetic m-cresol to be a very expensive commodity. Since it is known that mcresol can be produced selectively from o- or p-toluic acid, which is readily available from the corresponding xylene, by application of Keading’s Dow Phenol process, it was decided 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 investigate the mechanism of the reaction through the use of X-ray diffractometry, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectrometry (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 paddlewheel structure of Cu(II) carboxylates, when o-toluic acid was reacted with basic copper(II)carbonate and magnesium oxide in refluxing toluene. Apart from the expected four o-toluic acid entities forming the paddlewheel structure, the crystal structure also indicated another toluic acid molecule to be attached to each copper atom through the carbonyl of the carboxylic acid moiety. Extension of the X-ray crystallographic investigation to the copper salts of p-toluic acid, m-toluic acid, p-ethylbenzoic acid, and 2,6-dimethylbenzoic acid indicted all of these compounds, except the copper (II) salt of p-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 paddlewheel configuration, the extra two toluic acid molecules attached to the copper atoms in the all of 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 adjacent molecule leading to an infinite “polymer” type chain along the a-axis of the crystal, was observed. Evidence gathered from DSC, TGA, and MALDI-TOF MS investigations of the transformation of tetrakis(μ2-2-methylbenzoato)bis(2-methylbenzoic acid)copper(II) into the product, suggested that this copper benzoate rearranges and cleaves into o-toluic acid and 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 differences for the different steps in the reaction process, the salt of p-toluic acid displayed one continuous decomposition between 160 and 260 oC, thus rendering the identification of reaction intermediates at specific temperatures more or less impossible. In a process similar to that of cresols, resorcinol is commercially produced by selective formation of m-diisopropylbenzene followed by oxidative cleavage of the dihydroperoxide which is obtained through aerial oxidation of the diisopropylbenzene. While this process is used globally, it is hampered by large recycle streams arising from poor o/p selectivity during the alkylation of benzene as well as the limitation of low conversion (20%) in the oxidation step due to the explosivity of the hydroperoxide intermediate. Since it has been demonstrated that the Diels-Alder reaction could be applied to the synthesis of p-cresol from isoprene and vinyl acetate, application of this methodology to the synthesis of resorcinol, was subsequently investigated. Danishefsky’s diene (trans-1-methoxy-3-trimethylsilyloxy-1,3-butadiene), with the appropriate functional groups already trapped in the required enolic form, was selected as model substrate for the preliminary experiments with model dienophiles, methyl vinyl ketone 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 the reaction was extended to the more relevant methyl propiolate as dienophile, no direct Diels-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 from the reaction mixture in 5.51 and 5.74 % yields respectively. The formation of the phydroxybenzoate is explicable in terms of methanol elimination from the primary Diels- Alder product, while it is clear that the second product originates from conjugate addition of the formed hydroxybenzoate to methyl propiolate. While seemingly negative, the last Diels-Alder reaction, however, showed that the envisaged methodology could in principle be used for the preparation of resorcinol, but that care would have to be taken in order to avoid 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 reaction with an acrylate, the tendency towards methanol elimination might, however, be advantageous 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 form part of a future investigation. While negative from the point view of methodology for the synthesis of resorcinol, the Diels-Alder reaction between methyl propiolate and Danishefsky’s diene represents a new catalytic process for the preparation of methyl 4-hydroxybenzoate. This compound is widely used as a preservative in food, cosmetics and pharmaceuticals, while its free acid form (p-hydroxybenzoic acid), which is produced by Kolbe-Schmidt carboxylation of potassium phenolate with carbon dioxide, finds application in the liquid crystal industry. | en_ZA |
| dc.description.abstract | Afrikaans: Beide m-kresol en resorsinol is belangrike industriële uitgangstowwe vir die sintese van verskeie fenoliese produkte. Kresole word in ‘n proses soortgelyk aan dié vir die produksie van fenol berei deur die reaksie van tolueen met propileen om mengsels van o-, m- en p-isopropieltolueen te vorm. Die ooreenstemmende kresole, tesame met asetoon, word gevolglik via die hidroperoksiede ná lugoksidasie verkry. m- en p-Kresol se kookpunte verskil so min dat dit nie deur distillasie geskei kan word nie en skeiding van hierdie mengsels berus dus op omslagtige addukkristallisasie, derivatisering of chromatografiese prosedures, wat daartoe bydra dat suiwer sintetiese m-kresol ‘n baie duur kommoditeit is. Aangesien dit bekend is dat m-kresol selektief vanaf o- of p-tolueensuur, wat geredelik beskikbaar is vanaf die ooreenstemmende xileen, berei kan word deur gebruik te maak van Keading se Dow-Fenolproses, is dit besluit om hierdie metodologie as alternatief vir die sintese van suiwer m-kresol te ondersoek. Ten einde hierdie proses te optimiseer, is besluit om die meganisme van die reaksie met behulp van X-straaldiffraktometrie, termogravimetriese analise (TGA), differensiële skandeerkalorimetrie (DSK), infrarooispektrometrie (IR) en MALDI-TOF massaspektrometrie te ondersoek. X-straaldiffraktometrie het bevestig dat die beginpunt van die kopergekataliseerde proses tydens die omskakeling van o-toleensuur na m-kresol die vorming van tetrakis(μ2-2-metielbensoato)bis(2-metielbensoësuur)koper(II), met die tipiese wawielstruktuur van Cu(II) karboksilate, is wanneer o-toleensuur met basiese koper(II)karbonaat en magnesiumoksied in tolueen onder terugvloei verhit word. Buiten die verwagte vier otolueensuur entiteite wat die wawielstruktuur vorm, het die kristalstruktuur aangedui dat ‘n addisionele tolueensuurmolekuul deur die karboniel van die karboksielsuurmoïeteit met elke koperatoom geassosieer is. Uitbreiding van die X-straalkristallografiese ondersoek na die kopersoute van p-tolueensuur, m-tolueensuur, p-etielbensoësuur en 2,6- dimetoksibensoësuur het aangedui dat, buiten vir die koper(II) sout van p-tolueensuur, al hierdie verbindings strukture soortgelyk aan die van tetrakis(μ2-2-metielbensoato)bis(2- metielbensoësuur)koper(II) het. Alhoewel die struktuur van tetrakis(μ2-4- metielbensoato)bis(4-metielbensoësuur)koper(II) basies ook die wawielkonfigurasie vertoon, is die ekstra twee tolueensuurmolekules geassosieer met die koperatome in al die ander gevalle afwesig in die struktuur van hierdie verbinding. In hierdie geval is waargeneem dat interaksies tussen ‘n suurstofatoom van een molekuul en die koper van ‘n aangrensende molekuul tot oneindige “polimeriese” tipe kettings langs die a-as van die kristal lei. Getuienis uit DSK, TGA en MALDI-TOF MS ondersoeke na die omskakeling van tetrakis(μ2-2-metielbensoato)bis(2-metielbensoësuur)koper(II) na die produk, dui daarop dat die koperbensoaat by 164 °C herrangskik en in o-tolueensuur en koper(I) 2-metiel-6- {[(2-metielfeniel)-karboniel]oksi}bensoaat splyt. Dekarboksilering van laasgenoemde by 249.5 °C lewer o-tolueensuur en 3-metielfeniel 2-metielbensoaat, wat met hidrolise otolueensuur en die verlangde produk, m-kresol, lewer. In teenstelling met die kopersout van o-tolueensuur, wat duidelike temperatuurverskille vir die verskillende stappe in die reaksie getoon het, het die sout van p-tolueensuur slegs een aaneenlopende ontbinding tussen 160 en 260 °C getoon wat die identifikasie van reaksie-intermediêre by spesifieke temperature min of meer onmoontlik maak. In ‘n proses soortgelyk aan dié van kresole, word resorsinol kommersiëel berei deur die selektiewe vorming van m-diisopropielbenseen en die daaropvolgende oksidatiewe splyting van die dihidroperoksied verkry deur lugoksidasie van die diisopropielbenseen. Alhoewel hierdie proses wêreldwyd gebruik word, word dit beperk deur groot herwinningstrome weens die swak o/p-selektiwiteit gedurende die alkilering van benseen sowel as die lae omskakeling (20 %) in die oksidasiestap as gevolg van die plofbaarheid van die hidroperoksiedintermediêr. Aangesien dit bekend is dat die Diels-Alder reaksie vir die sintese van p-kresol vanaf isopreen en vinielasetaat gebruik kan word, is die toepassing van hierdie metodologie op die sintese van resorsinol dus ondersoek. Danishefsky se dieen (trans-1-metoksi-3-trimetielsilieloksi-1,3-butadieen), met die toepaslike funksionele groepe alreeds in die verlangde enoliese vorm vasgevang, is as modelsubstraat vir die aanvanklike eksperimente met model dienofiele, metielvinielketoon en butielakrilaat, gekies en die tot nog toe onbekende cis- en transprodukte, 4-asetiel-3-metoksiesikloheksanoon en butiel 2-metoksie-4- oksosikloheksaankarboksilaat, is, alhoewel in lae opbrengs (7.49 en 6.59 % en 7.53 en 9.66 %), verkry. Geen direkte Diels-Alder produkte kon egter geïsoleer word toe die reaksie uitgebrei is na die meer relevante metielpropiolaat as dienofiel nie en slegs 4-hidroksiebensoaat en metiel 4-{[(1E)-3-metoksie-3-oxoprop-1-en-1-iel]oksi}bensoaat is in 5.51 en 5.74 % opbrengs, respektiewelik, uit die reaksiemengsel geïsoleer. Die vorming van die p-hidroksiebensoaat kan verduidelik word in terme van methanol eliminasie uit die primêre Diels-Alder produk, terwyl dit duidelik is dat die tweede produk deur gekonjugeerde addisie van die gevormde hidroksiebensoaat aan metielpropiolaat gevorm word. Alhoewel oënskynlik negatief, dui die laaste Diels-Alder reaksie daarop dat die voorgestelde tegnologie in beginsel vir die bereiding van resorsinol gebruik sal kan word, maar dat voorsorg teen ongewenste metanolvrystelling getref sal moet word. Indien Chan se dieen [1,3-bis-(trimetielsilieloksi)-1-metoksie-1,3-butadieen] of ‘n ekwivalent daarvan vir die Diels-Alder reaksie met ‘n akrilaat gebruik sou word, mag die neiging tot metanoleliminasie egter voordelig wees aangesien dit in ‘n enkele stap die mono-gesilileerde resorsinol mag lewer. Die lewensvatbaarheid van die Diels- Alder strategie vir die sintese van resorsinol sal deel vorm van ‘n toekomstige ondersoek. Alhoewel negatief in terme van metodologie vir die sintese van resorsinol, verteenwoordig die Diels-Alder reaksie tussen metielpropiolaat en Danishefsky se dieen ‘n nuwe katalitiese proses vir die bereiding van metiel 4-hidroksiebensoaat. Hierdie verbinding het wye toepassing as preserveermiddel in kos, kosmetika en farmaseutika, terwyl die vry suur (p-hidroksibensoësuur), wat deur die Kolbe-Schmidt karboksilering van kaliumfenolaat met koolstofdioksied gevorm word, toepassing in die vloeibarekristal- industrie het. | af |
| dc.description.sponsorship | SASOL | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11660/2734 | |
| dc.language.iso | en | en_ZA |
| dc.publisher | University of the Free State | en_ZA |
| dc.rights.holder | University of the Free State | en_ZA |
| dc.subject | Dissertation (M.Sc. (Chemistry))--University of the Free State, 2009 | en_ZA |
| dc.subject | Cresol | en_ZA |
| dc.subject | Phenols -- Synthesis | en_ZA |
| dc.title | Development of alternative technology for the production of meta-substituted phenolic compounds | en_ZA |
| dc.type | Dissertation | en_ZA |